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M O NO G R A D H S.
No. 11.
MILWAUKEE,
Pharmaceutical Review Publishing Co.
1906.
The ‘Oolatile Oils: 1904.
...?Y. tº wº
I. W. BRANDEL.
MILWAUKEE,
Pharmaceutical Review Publishing Co.
1906.
7%, %~~~
SUBIECT INDEX.
enve-tº- &
Ó2 2%z,
4 - /ø –/ */
Page
Abies alba. ............. ............................ 6
“ pectinguta ................................... 6
“ Sibirica....................... ............... 8
Abietineae...........................................
Acacia fairnesiana ............................... 27
Ambrette, seeds, Oil of ............ * * * - - - - - tº s 35
Ambrosia artemisiaefolia................... 49
Amorpha fructicosa........................ ... 27
Andropogon citratus..................... 12, 47
& 4 nardus........... ............... 12
& 4 Schoenanthus................. 10
Angelica oil......................................... 42
Anise oil.............................. ............... 40
Anonaceae................................ . . . . . . . .---- 17
Apiol................................................... 15
Arctium lappa, War. minor............ ... 51
& C 4 4 Var. to mentOSa.......... 51
Artemisia herba alba......................... 50
$ 4 Vulgaris.......... ................... 50
Asarone............................................... 15
Bardana oil........................................ 51
Basil oil.............................................. 4.7
Bay oil................................................ 37
Bergamot Oil ..................... • * - - - - * * * * - - - - * * * * 31
Betula alba ........................................ 16
Betulaceae........................................... 16
Bitter almond oil............................... 25
BOld O leaves, Oil Of............................ 19
Buchu leaves, Oil Of............................ 29
Burseraceae..... ................................... 34.
Cajeput oil....................................... 38
Callitris quadrivalvis......................... S
Calumba root, Oil Of.......................... 51
Calyptranthes paniculata .................. 3S
Camphor oil........................................ 19
Canada Balsam.................................. 4.
Cananga oil. .................... ........ ........ 17
Canarium mauritiana. ...................... 35
Caprifoliaceae ..................................... 49
CaraWay oil........................................ 40
g & “ assay of......................... 40
Caricari elemi...................................... 34
Cassia, flowers, oil of......................... 27
Cedar oil............................................. 10
Cedrol.................................................. 1()
Celery leaves, oil of ............................ 40
Cinnamon Oil, assay of...................... 19
4 & “ Cassia...... ................... 20
{ { “ Ceylon ...'...................... 19
& & “ Japanese..................... 21
4 { “ laurenii....................... 21
Citronella oil...... ................................ 12
& & “ tests for........................ 13
Citrus aurantium................................ 31
Clove oil.............................................. 37
& & “ assay of.............................. 37
Colophonia elemi................................ 35
Colophonium mauritiana................... 35
Compositae......................................... 49
Copaifera guianensis.......................... 26
Page
Coriander oil....................................... 40
Cruciferae ............................................ 22
Cypress oil ......................................... 9
Dill oil ................................................ 42
Diosma. Succule” ta.............................. 29
Dog Fennel oil.................................... 49
Elder blossoms, oil of........................ 49
Elemi, Oil of........................................ 34
Erythroxylon monogynum................ 29
Erythroxylaceae.............. .................. 29
Essence de Bruyere............................. 51
Eucalyptus globulus.......................... 39
© tº microcorys....................... 40
& 6 punctata.......................... 40
4 & resinifera........... .............. 39
Eupatorium capillifolium....... • e s - - - - 49
& ſº foeniculaceum.................. 49
Fennel oil .................. ........................ 4-1
Geraniaceae........................................ 28
Geum urbanum................................... 26
Ginger oil............................................ 13
Ginger grass oil ................................. 11
Gouft oil ............................................. 51
Gramineae....... ................................... 10
Hypericum perforatum ...................... 35
Hyptis fasciculata..... ........................ 49
& 4 Salzmanni....... : - - - - - - - - - - - - - - - - - - - - - - - 49
“ Spicata.................................... 48
Jasmine oil......................................... 43
Jateorhiza palmata ........................... 51
Juniper berries, Oil Of........................ 10
Kuro-moji oil..................................... 22
Labiatae............................................. 44
Lauraceae........................................... 19
Laurel leaves, oil of............ .............. 21
Leguminosae....................................... 26
Lemon oil........................................... 30
{ % “ assay of ........................... 30
Lemon-grass oil................................. 12
Limette oil.......................................... 32
Linaloe, Oil of..................................... 35
Lippia geminata................................. 44
4 & microcephala........................... 43
4 & urticoides.............. ................. 44
Malvaceae........................................... 35
Matico oil........................................... 14.
Mentha Citrata................................... 46
jaVanica........................ .... .... 46
• { lanceolata.............................. 46
Mesosphaerum spicatum .................... 48
Mignonette fio wers, oil Of.................. 23
Monard a citriodora............ ............... 45
4 & didyma................................ 45
Monimiaceae....................................... 19
Page
Mountain laurel oil............................ 22
Mustard oil................. ....................... 22
§ { “ assay of.......................... 22
Myristicaceae...................................... 18
Myrtaceae........................................... 36
Neroli oil ................. .......................... 32
& 8 “ assay Of.................. .......... 33
Nikkei oil...................................... .... 21
Nutmeg O 1.......................................... 18
Ocimum basilicum.............................. 47
4 * Cà, I’Il OSll Ill .... ......... . . . . . . . . . . . . . . 48
$ 4 micranthum.......................... 48
Oleaceae.............................................. 43
Opopanax, oil of..............................., 34
Orange branches, oil of ..................... 31
Oregon Balsam................................... 5
Patchouly oil...................................... 7
Pelargonium capitatum ..................... 28
£ 6 Odoratissimum .............. 28
Peltodon radicans............ ................. 49
Pepper oil ................. ............ ............ 14
Peppermint Oil, English..................... 46
4 & “ French...................... 45
& 4 " Javanese................... 45
Pimenta Oil......................................... 36
Pine needle Oil, German..................... 7
4 & 4 * Russian................. ... 7
6 & 4 & “ Siberian..................... 8
Pine tar oils....................................... 5
4 & “ oil, American....................... 5
4 & “ “ Finland.......................... 6
4 & “ ” test for........................... 2
‘‘ ‘‘ ‘‘ Jeffreyi ........................... 5
Pinus halepensis................................. 3
“ longifolia.................................. 4.
“ Sabiniana................................. 5
“ SilveStris................................... 6, 7
“ Strobus..................................... 7
Piper angustifolium............................ 1.5
4 & famechoni............. .................... 14
Piperaceae........................................... 14
Primula camphor....... .......... ........... 43
& 4 root oil................................. 43
Primulaceae........................................ 3
Raspberry oil...................................... 26
Resedaceae.......................................... 23
Rosaceae............................................. 23
Rose oil............................................... 23
Rosemary oil...................................... 44
Rutaceae........... ................................. 29
Sage oil.............................................. 45
Sambucus migra.................................. 49
Sandalwood oil......... ........................ 16
{ { “ African..................... 17
Sandarac Resin oil...... ......................
Santalaceae......................................... 16
Scheih oil............................................ 51
Tacamhaca elemi............................... 34
Tanacetum Vulgare............................ 50
4 & boreale........... ................. 50
Tansy oil............................................ 50
Thuja articulata..... ........ .................. 8
Thuja oil....................... ..................... 9
Thyme oil........................ .................. 45
Turpentine oil, American................... 1
( & “ test for...................... 2
& 4 ‘‘ from Canada Balsam 4
© [. “ Greek.........................
& 4 “ Indian. ................ ..... 4.
& 4 “ from Oregon Balsam 5
Umbelliferae........................................ 40
Unona latifolia ...................... ............ 17
* { Odorata ................. ......... ....... 17
Verbena oil......................................... 44
Verbenaceae .................................... .. 44
Vetiver oil........................................... 1()
Viola tricolor...................................... 36
Violaceae............................................. 35
Violet flowers, oil of .......................... 35
Water fennel oil ............................. ... 41
Weymouth Kiefernadeloel.................. 7
Worm Wood oil................................... 50
Ylang-Ylang oil.................................. 17
Zingiber Officinale....... .... ............ ..... 13
Zingiberaceae................................... .. 13
4. American Oil (Spirit) of Turpentine. G.-H...-K., p. 239.
Properties. According to Vézes and Mouline 1 turpentine oil and
absolute alcohol are miscible in every proportion and do not separate
even when the temperature is lowered considerably. Solutions of
turpentine oil and aqueous alcohol cannot be so cooled without
separating. The separation-temperature at constant pressure depends
upon the strength of the alcohol and the proportion of the quantities
of alcohol and turpentine oil. The authors have determined the
separation-curves of a large number of mixtures of oil of turpentine
and aqueous alcohol of various degrees of concentration and by
combining the separation-curves thus obtained, have ascertained
the separation-plane of the ternary mixture oil-alcohol-water.
By heating equal parts of oil of turpentine and salicylic acid to
130° for 50 hours, and removing the excess of acid with NaOH, and
the liquid fractionated under diminished pressure, Tardy 2 obtained
a crystalline ester which upon saponification yielded borneol. The
ester melted at 44–45°; ap = —34° 20'.
When 10 grams of phosphorus are allowed to stand with 100
grams of oil of turpentine for 2 hours at 50°C, there results, accord-
ing to Minovici, 8 a white wax-like precipitate, which upon analysis
corresponds to the formula C10H15PO(OH)2. It does not ignite
spontaneously in the air, but when heated burns with a luminous
flame, giving rise to a garlic-like odor.
Adulteration. The determination of the iodine absorption num-
ber, is recommanded by Worstall 4 as a reliable test to detect the
adulteration of oil of turpentine with rosin oil, kerosene, wood tur-
pentine etc. The method is as follows:
About 0.1 gram of the sample is weighed out from a dropping bottle
into a glass stoppered bottle, 40 cc. of Hübl’s solution added and th
1 Bull. Soc. Chim. (3) 31, p. 1043.
2 Journ. de Pharm., (6) 29, p. 57.
3 Pharm. Centralh. 45, p. 532,
4 Journ. Soc" Chem. Ind. 23, p. 302.
2 THE WOLATILE OILs : 1904.
tightly stoppered bottle set away over night. The excess of iodine is then
titrated back.
The iodine absorption number for rectified turpentine oil Was
found to be 377; for rosin oil, 97; for kerosene 0; for wood tur-
pentine 212. -
Adulterations with rosin oil and kerosene can, therefore, be
readily detected by this method even if added only in small quanti-
ties. The adulterations with wood turpentine in small quantities
cannot be detected. However, the cost of rectified wood oil is SO
little below that of oil of turpentine, that if used as an adulterant
for the latter, it is usually added in the proportion of 25–50 percent
to be profitable and such adulteration is easily shown by the
decreased iodine number. A turpentine ol with an iodine absorption
number of less than 370, should be suspected.
McCandless 5 claims, however, that the iodine absorption test can
not be relied on, and recommends a modification of Armstrong's
method (polymerisation with conc. sulphuric acid and subsequent
steam distillation), by which an adulteration of less than 5 p. c. can
be detected. The method is as follows:
100 c. c. of oil are gradually mixed, with thorough shaking and cooling,
with 50 c.c. conc. sulphur c acid; 25 c. c. of water are then added and the mix-
ture submitted to steam distillation. As soon as the total distillate
amounts to 100 c. c. the distillation is interrupted, and the volume and
index of refraction of the separated oil ascertained. The oil is then treated
with an equal volume of fuming sulphuric acid, the mixture poured into
cold water and the separated oil distilled with water vapor in the same
manner as the first time. This same process is carried out a third time,
but with double the volume of fuming sulphuric acid. After each distillation
the volume and index of refraction of the oil are determined.
In the case of pure oil of turpentine the refractometer number
determined at 25° with Zeiss's butter-refractometer is never less than
30, while the presence of even 1 percent of petroleum lowers the re-
fractometer number after the third polymerization to 25 and after
further polymerization to 22.
To detect pine tar oil in turpentine oil, McCandless 6 proceeds as
follows:
When the absence of petroleum oil has been proven, 100 c. c. of the oil
of turpentine are distilled very slowly and the refractometer number of the
5 Journ. Am. Chem. Soc. 26, p. 77.
6 loc. cit.
ABIETINEAE. sº 3
first 0.5 c. c. of the distillate determined. In the case of pure turpentine
oil, the refractometer number should not be less than 60. If this test does
not show any adulteration, the distillation should be continued, and the
refractometer number of the 97th and 98th c. c. fraction determined. In the
case of pure turpentine oil, this should not be more than 77. *
Herzfeld 7 also recommends the determination of the refracto-
meter numbers as a reliable method to detect adulterations in oil of
turpentine. The detection of pine tar oils, can readily be accomp-
lished by shaking the suspected oil with a solution of sulphur dioxide.
If pine tar oil is present to an extent of not less than 10 p. c. the
oily layer will turn yellowish green.
According to Utz 8 great quantities of Russian oil of turpentine
are sent to America, where it is purified and mixed with American
turpentine and then sold in Germany for pure American oil of tur-
pentine.
7a. Greek Turpentine Oil.
Origin and Prep a ration. The oleo-resin from Pinus hale-
pensis, a species growing in the eastern Mediterranean countries,
yields about 20-22 percent of oil. The bulk of the commercial oil is,
however, not distilled from the oleo-resin direct. The oleo-resin is
first of all added, by the wine manufacturer, to the grape juices.
in order to improve the keeping qualities of the wine and also to
impart to the wines the much desired resinous taste. From the dregs
of the wine containing the resin, the oil is then distilled with steam,
and the residue is worked up for colophony and calcium tartrate.
Properties. Greek oil of turpentine has a pleasant wine-like
odor, due to its method of production. A sample of oil examined by
Utzº was found to have a specific gravity of 0.86342 at 15° C.;
ap (in 200 mm. tube) = + 77.34°; index of refraction = 1.4678,
The bulk of the oil boils between 150–155°, leaving only a slight
residue. It is soluble in 12 parts of 90 percent alcohol.
According to Dambergis 10 the oil has a specific gravity of 0.8672
at 15° C.; ap (in 200 mm, tube) = + 73.4°; boiling point 155–157°.
An examination of the oleo-resin by the same author gave the follow-
ing results: — colophony 78.57 p. c.; oil 17.04 p. c.; loss at 100°
14.04 p. c.; ash 0.14 p. c.; acid number 149; ester number 6;
saponification number 155.
7 ztschr, für öffentl. Chem. 10, p. 382.
8 Apoth. Ztg. 19, p. 678.
9 Apoth. Ztg., 19, 628,
10 Oesterr, Che m, Ztg, , 1904.
4. THE WOLATILE OILS : 1904.
7b. Indian Oil of Turpentine.
Origin and Prep a ration. Considerable attention is being
given towards fostering the production of turpentine oil in India,
The annual reports of the Forest Dept in Indial 1 show that the oil
and resin have been manufactured to a greater or less extent for
some years. The industry is confined to the pine forests of the
Himalayas in the United Provinces and the Punjab. In the United
Provinces, the first distillery was erected in the Imperial Forest
School, Dehra, Dun, in 1888. Two more distilling stations, more
favorably situated on account of their proximity to the forests, were
erected, one in 1895 at Naina Tal and the other in 1899 at Nurpur,
in the Province of Punjab. The crude oleo-resin is collected from the
Chir pine, Pinus longifolia. The trees are tapped soon after the
rains are over in October. Cuts or “blazes' are made in the trunk of
the tree, at the base of which pots are placed to catch the exuding
resin. In the lower forests of Kumaon, the oleoresin begins to flow
in March and as the warm weather advances the flow increases, the
greatest amount being obtained in June. The crude oleo-resin yields
from 14–18 percent of oil. The resin as well as the oil find a ready
market. 43,000 trees have been tapped in a single year. No exami-
nation of the oil has as yet been made. An examination was made
this year in the writers laboratory.
9. Turpentine Oil from Canada Balsam. G.-H...-K., p. 251.
Properties. Dowzard 12 has determined the constants of pure
Canada balsam and also of the oil, with the following results:
Canada Ba1san1.
Sp. gr. at 15.5°....................... * * * * * * * * * * * * * * * * * s e o e º e a e = * ().987 to 0.994
O'D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * + 1o to + 49
Index of refraction at 20° C. ............................. 1.518 to 1.521
4.
Oil from Canada Balsam.
Sp. gr. at 15.5°C. ............................................. 0.862 to 0.865
C/D . . . . . . . . . . . f • * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * . . . . . . . . . . . . . . . — 26° to — 29
Index of refraction at 20° C. ............................. 1.472 to 1,477
1 1 Chem. & Drugg., 65, p. 831.
12 Chem. & Drugg., 64, p. 439.
PINE TAR OILs. – KIENCELE. 5
9a. Turpentine Oil from Oregon Balsam.
Origin. The twigs and cones of the tree from which the Oregon
Balsam is collected, have been identified, according to Rabak, 18 as
belonging to Pseudotsuga mucronata, Sudworth.
Properties and Composition. Several commercial samples
of Oregon Balsam were examined and the following results obtained:
Sp. gr...................................... 0.994. 1.01 0.985
GD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . — 19 16’ + 4° 13' + 2° 30'
Acid number............................ 102 103 116
The oil obtained by steam distillation had an agreeable terebin-
thinate odor and the following constants:
Sp. gr................................... 0.873 0.857 , 0.822
“bº” — 39° 55' — 37° 46' — 34° 37'
About 80 p. c. of the oil boiled below 160° C., and consisted
principaly of l-pinene (nitrosochloride m. p. 106; nitrosopinene m. p.
125°).
According to Dowzard, 14 the balsam has a sp. gr. = 0.993,
ap = — 3°12', index of refraction = 1.5123. The oil obtained by
steam distillation had the following constants: sp. gr. = 0.8652,
ap = — 37°24', index of refraction = 1.4670.
14. Oil from Pinus Sabiniana. G.-H...-K., p. 253.
Origin. According to Wenzell, 15 Pinus Jeffreyi, as well as Pinus
Sabiniana, yield an oil consisting principally of the hydrocarbon
abietene. The oil from Pinus ponderosa, which was also supposed
to consist of abietene, does not contain this hydrocarbon, but a
terpene.
14a. Oil from Pinus Jeffreyi. See 14.
PINE TAR OILS. — KIENCELE.
15a. American Pine Tar Oil.
Production. During recent years the destructive distillation
of pine stumps, light wood, slabs, etc., for the production of pine
tar oil, wood naphtha, wood spirit, rosin oil, tar, creosote and char-
coal, in North Carolina and Georgia has met with a more marked
success. This has been partly brought by improvements in the
processes and apparatus employed. During 1904, patents on im-
13 Pharm. Rev., 22, p.
p. 293.
14 Chem. & Drugg., 64, p. 439. k
15 Pharm. Rev., 22, p. 408.
6 THE WOLATILE OILS : 1904.
proved process and apparatus were granted to Mallonee 1 and to
Clark & Harris.” For a detailed description of the apparatus and
process employed, the patent reports should be consulted.
Pro per ties and Co m position. Two samples, ‘H’ and ‘M’,
manufactured in Georgia, were examined by Kremers. 8 The former
was colorless, the latter had a slight yellowish tint. In a general
way, they had a terebinthinate odor, but both betrayed their origin
by a slight empyreumatic odor. Besides, the odor reminded of
lemon. Sample ‘H’ had a sp. gr. of 0.856; an = + 13° 40' and
sample ‘M’ had a sp. gr. of 0.860; ap = + 13°42'. Upon being
distilled with steam after being shaken with a 5 p. c. caustic soda
solution, 98 p. c. of sample ‘H’ were recovered and 94 p. c. of sample
‘M’. The rectified oils had the follows constants:
‘H’ sp. gr. 0.854; an = + 14° 25'
r ‘M’ sp. gr. 0.854; an = + 13° 42’
The bulk of sample ‘M’, consisting of pinene, boiled between
158—160. The presence of dipentene was also highly probable.
18. Pine Tar Oil from Finland. G.-H...-K., p. 257.
O rig in and Prep a ration. Pine tar oil is produced in Fin-
land by the destructive distillation of Pinus silvestris L. 4 in order
to obtain at the same time other products, especially the tar. The
crude oil has a black color, and upon purification by distillation, is
obtained colorless, strongly refractive and possessing a tar-like odor.
The oil is largely used in Finland as unpurified turpentine oil both
for technical and medicinal purposes. It differs from true turpentine
oil by having a slight reaction capacity towards chlorine and iodine.
20. Oil from Cones of Abies Alba. G.-H...-K., 259.
A Swiss distillate from the cones of Abies alba, Miller, Abies
pectinata, also called Ol. Templini, has been examined by S. & Co.5
Laurinic aldehyde, yielding a semicarbazone m. p. 101.5–102.5°,
was identified. Upon oxidation laurinic acid, m. p. 43°, was ob-
tained. In addition to laurinic aldehyde, a second aldehyde, called
decylic aldehyde, appears to be present. Its semicarbazone melted
§ 3 ; #########,”;.
Pharm. Rev., 22, p. 150. .
Pharm. Centralh., 45, p. 859.
S. & Co.'s Rep., April–May, 1904, p. 77.
:
PINE TAR OILs. – KIENELE. 7
at 93–95°. The odor of the oil is due to the presence of these ali-
phatic aldehydes.
23. Pine Needle Oils from Pinus silvestris. G.-H...-K., p. 262.
German Pine needle Oil. Origin. Troeger and Bentin 6
distilled the young needles of Pinus silvestris, collected in the spring
of the year, in order to compare the composition of the oil, with
that of an oil obtained from the old needles.
Properties and Composition. The oil was almost colorless
and had a sp. gr. of 0.871 at 20° C. It was found to contain 3.23
p. c. of ester which was calculated as C10H170 (COCH3), the acetic
acid having been identified. The oil also contained 9.3 p. c. of an
alcohol, which was not identified. It was not borneol, which is found
in the oil from old needles. The oil contained d-pinene (nitroso-
chloride m. p. 107–109; nitrolamine m. p. 122). Sylvestrene and
cadinene, both of which have been found in the oil from old needles,
could not be identified in this oil.
Russian “Kiefer n a del úl.” A sample of this oil examined by
Schindelmeiser 7 was found to be optically inactive and contained
d-pinene (apis° = +3° 51’; sp. gr. at 18° = 0.858); l-limonene
(b. p. 174–178: an 18° = —8°28'; sp. gr. at 18° = 0.851); 3 p. c.
of bornyl acetate and some cadinene.
23a. Needle oil from Pinus strobus. Weymouth Kiefer-
madeloel.
Origin. The young needles of Pinus Strobus, collected in spring,
yielded a colorless oil. 8 s
Properties and Composition. The oil had a sp. gr. Of
0.9012 at 15°; index of refraction at 20° = 1.48274; ap (200 m m.
tube) = — 39.7°. About two-thirds of the oil distilled over from
154—170°, l-pinene was identified (nitrosochloride m. p. 103°, nitro-
lamine 122°). The original oil contained 8.4 p. c. of ester calculated
as C10H17O.CH3CO, and 5.2 p. c. of free alcohol, C10H1s0, which
could not be identified. Sylvest rene and borneol, which have been
found in the oil from the old needles of Pinus strobus, could not be
identified in the oil from the young needles.
6 Arch. d. º 242, p. 521.
7 Apoth. Ztg., 19, p. 816,
s Arch. d. Pharm. 242, p. 254.
8 THE WOLATILE OILS : 1904.
27. Siberian Pine Needle Oil. G.-H...-K., p. 265.
Properties and Co m position. Golubew 9 has isolated
l-bornylacetate and l-camphene in crystalline form, from the Oil of
Abies Sibirica. The former was found to the extent of 43.96 p. C.,
the latter about 10 p. c. The bornylacetate was isolated in the form
of rhombic crystals melting at 223–224° C. at 758 mm. A 15.5
p. c. solution in alcohol gave [a] p?0° = — 45.47° and a 19.6 p. c.
solution gave [a]n 10° = — 44.02. The l-borneol obtained from it
had the following constants: m. p. 204°C.; b. p. 210°C. at 779 mm.,
15.22 p. c. alcoholic solution, [a]p 10° = — 36.14°, and 15.4 p. c.
solution, [a] pio° = — 37.77. Upon oxidation, the l-borneol was
converted into 1-camphor, m. p. 188–189° C., b. p. at 757 mm.
204° C. [a]p 20° (9.97 p. alcoholic solution) = —41.11°.
The l-camphene, obtained in crystalline form, melted at 40–41°
C. and boiled at 159–160° C. [a] p (1.76 p. c. alcoholic solution)
= — 85°.
Several commercial samples of the oil were examined by Schindel-
meiser. 10 The sp. gr. at 17° C. varied from 0.911–0.915, and the
optical rotation at 17° C. from — 29° 18' to — 34° 30'. The sp. gr.
of authentic oils was never found less than 0.918 and ap never less
than — 39° 40'. About 22–30 p. c. of the commercial oils boiled
between 170–190° C. Only 19.5–30 p. c. of bornyl acetate was
found while the ester content of authentic oils was between 35–42
p. c. A fraction of hydrocarbons was obtained, b. p. 174–180°,
a p17° = –18° 28′, which probably contained the optically inactive
dipentene. These results seem to show that the commercial oils are
adulterated with turpentine oil or with pine needle oil.
32. Sandarac Resin Oil. G.-H...-K., p. 267.
Origin. By distilling the sawdust of Callitris quadri Valvis Went.
(Thuja articulata, Wahl) of Algeria, which yields the sandarac resin,
Grimal 11 obtained 2 p. c. of a volatile oil.
Properties and CO m p Osition. The oil is of a red-brown
color and has a phenol-like odor. It has a sp. gr. of 0.991 at 15° C.,
and is soluble in all proportions in 80 p. c. alcohol, which solution
rotates the plane of polarized light to the left. It boils between 230°
9 Journ. russ. phys. Chem. Ges., 36, p. 1096.
10 Apoth. Ztg., 19, p. 815.
11 Compt. rend. 139, p. 927.
PINE TAR OILs. – KIEN(ELE. 9
and 306°, leaving a resinous residue. It contains about 5 p. c. of
s phenols, consisting of carvacrol and hydrothymoquinone. Thy-
moguinone was also detected.
33. Thuja Oil. G.-H...-K., p. 267.
Composition. Wallach 1” has established the presence of two,
possibly of three thujones. Thuja oil contains principally a-thujone.
33. Oil of Cypress. G.-H...-K., p. 269.
Properties. The oil examined by Schimmel & Co.18 had the
following constants: di R8 = 0.8922: ap = + 16° 5'; no 20°=1.47416.
The oil was insoluble in 10 parts of 90 p. c. alcohol.
An oil of their own distilling had a sp. gr. of 0.8916 at 15°;
ap = + 16° 27' and was soluble in 2.5 volumes of 90 p. c. alcohol.
A French distillate had a sp. gr. of 0.8680 at 15°; an = + 26° 31'
and was soluble in 5.5 parts of 90 p. c. alcohol.
Composition. In the first few drops of the oil distilled under
diminished pressure, furfurol was identified. The hydrocarbon oil
contained d-pinene (nitrosochloride m. p. 102, nitrolbenzylamine m.
p. 122); d-camphene, identified by means of the isoborneol reaction;
d-sylvestrene (dihydrochloride, m. p. 72°); cymene (p-oxyisopropyl
benzoic acid, m. p. 155–156°); l-cadinene (dihydrochloride m. p.
117–118°). The presence of fenchene is not improbable, although
not positively identified. Reactions for limonene, dipentene and
phellandrene gave negative results.
The fraction of oil boiling at 80°–90° (3 to 4 mm.) contained a
ketone, its semicarbazone melting at 177—178°, which was not
further identified. Fraction 70–85° (3 to 4 mm.) contained an alcohol
which in all probability is sabinol. Upon oxidation, an acid was
obtained melting between 130–140°, which undoubtedly contained
a-tanacetogene dicarbonic acid, m. p. 140°, the oxidation product of
Sabinol.
Fraction 90–95° (4 mm.) contained a terpene alcohol, yielding a
phenylurethane m. p. 142–144°. The original oil contained about 8
p. c. of esters, principally d-terpinol, m. p. 45°, as acetic acid ester.
Waleric acid and a third acid, obtained in the form of long silky
needles, m. p. 129, were isolated.
*.
12 Ann., 336, p. 247.
18 S. & Co.'s Rep., April, 1904, p. 38; Oct., 1904, p. 23.
10 THE WOLATILE OILS : 1904.
Cypress camphor, m. p. 86°–87°; b. p. 290–29.2°, constitutes
about 15° p. c. of the oil. Strong formic acid converted this sub-
stance quantitatively to a hydrocarbon C15H24 (nitrosochloride,
m. p. 100–102°). The distillation residue of cypress oil forms a
viscid brown resin having a ladanum-like odor.
Soltmann, 14 has again tested the value of cypress oil as a remedy
for whooping cough with very favorable results.
37. Oil of Juniper Berries. G.-H...-K., p. 270.
Properties. Although oil of Juniper berries usually shows a
laevo rotation, two oils originating from Russia, 15 showed a dextro-
rotation of +7° to +8°. This deviation in the optical behavior
appears to be solely due to the origin of the oils, for in other re-
spects, the oils did not differ from a normal distillate.
42. Oil of Red Cedar Wood. G.-H...-K., p. 276.
Composition. S. & Co.1% have determined that the cedar cam-
phor or cedrol present in cedar oil is actually, as has hitherto been
assumed, the optically active modification of the inactive cypress
camphor. Both substances melt at 86–87°. Strong formic acid
converts both substances quantitatively to a hydrocarbon C15H24.
These two hydrocarbons have the same boiling point and sp. gr.
(b. p. 264°; sp. gr. 0.9367 at 15°), but differ in their optical rota-
tion. The hydrocarbon from cedar camphor is laevorotatory, an =
–85° 32', while the hydrocarbon from cypress camphor is dextro-
rotatory, an = + 94° 3'. In chemical properties, the two hydro-
carbons are identical.
OILS OF THE GRAMINEAE.
40. Oil of Vetiver. G.-H...-K., p. 289.
Haensel 1 obtained from Vetiver roots 1.3 p. c. of a brown oil
which had an acid reaction. It is soluble in 1.1 parts by weight of
80 p. c. alcohol. Sp. gr. = 1.0244; 40 = +25.56°; acid number 39;
}
saponification number 50; acetylization number 104.
46. Oil from Andropogon Schoenanthus L. G.-H...-K., p. 281.
Origin. Roure-Bertrand Fils” have examined an oil said to
have been obtained from Andropogon Schoemanthus from New Cale.
14 S. & Co.'s Rep., April–May, 1904, p. 37.
15 S. & Co.'s Rep., Oct.–Nov. 1904, p. 50.
16 Ibidem, p. 25.
1 Ber. H. Haensel 1904 (I), p. 25.
2 Roure-Bertrand Fils Bull., April 1904, p. 37.
GRAMINEAE. 11
donia. This plant is also the source of Palmarosa 3 or East Indian
geranium oil. The New-Caledonian oil, however, differs from the
East Indian geranium oil, in that the former consists largely of
citral, while the latter consists almost entirely of geraniol, the alco-
hol corresponding to citral. -
Properties and Composition. The oil has a sp. gr. of
0.92.17 at 20° C. It contained 43.2 p. c. of citral and 7 p. c. of an
aldehyde possessing the characters of citronellal. 5.5 p. c. of the oil
was an ester, calculated as geranyl acetate, and 10.2 of p. c. alcohol,
calculated as geraniol.
47. Ginger-grass Oil. G.-H...-K., p. 285.
Properties and Composition. Ginger-grass oil, which was
apparently genuine, although its source was unknown, examined by
Schimmel & Co., had the following constants: dis? = 0.9380:
ap = +22° 40'; saponification number 24; saponification number
after acetylisation 166. Soluble in 2.3 parts of 70 p. c. alcohol, the
solution becoming cloudy upon the further addition of alcohol. At
5 to 6 mm, pressure, the oil distilled over from 50° to 100°.
A fraction 44° to 45° at 4 mm. pressure, 175° to 176° at 754
mm. pressure, d.15 = 0.8565; ap = + 44°40', contained phellandrene
(nitrite m. p. 120°). Fraction 175°–180°, contained d-limonene
(nitrosochloride, m. p. 178–180°; nitrolbenzylamine m. p. 93°) and
dipentene (nitrosochloride m p. 103–104°; a-dipentene nitrolbenzyl-
amine, m. p. 110°; a-dipentene-nitrol piperidide 153°).
The saponified oil contained geraniol, b. p. 229–230° (diphenyl-
urethane, m. p. 82) and an alcohol having the following constants:
b. p. 94–95° at 5 mm.; d.15° = 0.951; an = + 13°46’: np = 1.49582
at 20°. Upon analysis the alcohol was found to have the formula
C10H16O. No crystalline derivatives could be obtained. Upon oxida-
tion an aldehyde, C10H140, whose semicarbazone melted at 198°–
198.5°, was obtained. Further oxidation yielded an acid of the
melting point 132°.
Walbaum & Hüthig, 4 have found this alcohol to be a dihydro-
carvedl which has the following properties: b. p. 228—229° at
755 mm.; d.15° = 0.9336; an = + 12° 5'; no.20° = 1,49761.
The oil contains about 0.2 p. c. of an aldehyde, C10H16O,
having the following constants: b. p. 76–78° at 5 mm.; 221°–224°
4. G.-H...-K., p. 281.
5 Chem. Ztg., 28, p. 1143.
12 THE WOLATILE OILs.
at 754 mm.; d.15° = 0.9851; an = +0°; nº.20°= 1,47348. It yields
the following derivatives: semicarbazone, m. p. 169–170°; semi-
oxamazone, m. p. 244–245°; phenylhydrazone, m. p. 68°; Oxime,
m. p. 115–116°. When left standing exposed to the air, it oxidizes
into a leafy crystalline acid C10H16O2, m. p. 106 to 107°, which is
identical with the acid isolated from the liquid resulting from the
saponification of the oil. The aldehyde is probably a cylic aldehyde.
48. Lemon-grass Oil. G.-H...-K., p. 285.
Origin. A correspondent 5 of the “Madras Mail” calls the
attention of planters to the possibility of making a profitable side-
industry out of the cultivation of Andropogon citratum, which grows
freely on the hills in southern India.
Properties. Schimmel & Co. 6 examined a sample of oil ob-
tained from the Botanical Gardens of Victoria (Cameroons). The
oil was obtained from some experimentally cultivated andropogon
grasses, and was thought to be citronella oil. The properties and
composition, however, show that it is almost identical with lemon-
grass oil. This again emphasizes the fact that the andropogon
grasses are frequently mistaken one for the other.
The oil had a yellow color and a powerful, pleasant aroma.
Sp. gr. at 15° = 0.8929; ap = –0°8'. It does not form a clear
solution with 70 p. c. alcohol and the solutions in 80 p. c., 90 p. c.
and even absolute alcohol, which are at first clear, gradually become
cloudy upon the further addition of alcohol. The oil contains 84
p. c. of citral.
A sample of Oil of Andropogon citratus from the Comoras was
examined by Roure-Bertrand Fils. 7 The oil had a specially fine odor
and contained 67 p. c. of citral, ap = –0° 6’.
50. Citronella Oil. G.-H...-K., p. 291.
Origin. There are two plants, according to Sawer,s which yield
the Ceylon citronella oil of commerce, viz. Andropogon nardus, var.
Snilagiricus, and Andi'Opogon Inardus, var. genuinus Hack. The
former grows wild, and is commonly called ‘Maana grass'. The lat-
ter, locally called ‘Pangrii Maana’ is a cultivated plant. About
40,000–50,000 acres of citronella grass are under cultivation.
5 Proc. A. Ph. A., 52, p. 861.
6 S. & Co. Rep., Oct.–Nov., 1904, p. 52.
7 Roure-Bertrand Fils, Bull April, 1904, p. 41.
8 Chem. & Drugg., 65, p. 179.
ZINGIBERACEAE. 13
An oil from Montserrat, reported to have been obtained from
Adropogon nardus, L. var. genuinus, is called lemon-grass oil.9 This
is undoubtedly due to the fact that like the true lemon-grass oil,
this oil contains a very large percent of the aldehyde citral, differing,
thereby, from the citronella oil which contains the aldehyde citron-
ellal.
Properties. The oil has a sp. gr. of 0.906 at 15° C.; [a]n =
—0° 10'. It is insoluble in 70 p. c. alcohol and contains 74.6 p. c.
of citral. ,
Adulteration. The examination of a large quantity of citro-
nella oil shows that this oil is commonly adulterated with petroleum.
Schimmel and Co. 10 recommend a modification of their method
(solubility in 80 p. c. alcohol at 20°C.) of judging citronella oils, in
order to detect the adulteration with small percentages of the some-
what soluble Russian petroleum.
To the oil to be examined, 5 p. c. of Russian petroleum is added, and
the behavior of the mixture towards 80 p. c. alcohol is then watched.
An oil which was pure before the addition of 5 p. c. of Russian petroleum,
will under these conditions, still pass the test. The oil should be soluble
in 1 to 2 volumes of 80 p. c. alcohol at 15°–20° C.
Bambier 11 has devised a method, to detect adulterations in citro-
nella oil, which is quantitative as well as qualitative. This method
is as follows:
A mixture of exactly 2 c. c. pure cocoanut oil free from acids, and 2 c. c.
of the citronella oil to be examined, is shaken in a suitable graduated glass
tube, at 29° to 30°, for one minute, with 20 c. c. alcohol of 83 p. c. by
weight (dē = 0.8273), and is then centrifuged for 4 to 1 minute. By
multiplying the increase in the volume of the cocoanut oil by 50, the per
cent of adulterant is found.
OILS OF THE ZINGIBERACEAE.
72. Ginger Oil. G.-H...-K., p. 313.
Origin a n d Prep a ration. According to Zimmermann, 1 the
mother plant of ginger, Zingiber officinale, Rose, which is indigenous
to tropical Asia, is cultivated in many countries of the tropics. The
rhizomes of this plant yield, according to the country and soil in
9 Pharm. Journ., 73, p. 610.
10 S. & Co., Rep. April–May, 1904, p. 28.
11 Proc. Chem. Soc., 19, p. 292; also Report S. & Co., Apr. 1904, p. 29 : ibidem :
Nov. 1904, p. 20.
1 Communication from Biol. Agric. Institute, Amani 1904, No. 28.
14 THE WOLATILE OILs.
which they are grown, different quantities of essential oil; whereas
African ginger yields 2–3 p. c., Jamaica, ginger only yields 1.075 p. c.
of oil. A sandy loam which is also chalky is the most favorable soil
for the cultivation of ginger. It is grown exclusively from pieces of
rhizomes, which are kept in dry places, and which shortly before
sowing are cut up in bits, 1% to 2 inches long, each piece having at
least one bud. The fields are laid out in the same manner as a
potato field, most suitably with ridges 1 foot and furrows 2% feet
wide. The pieces are placed in holes about 3 to 4 inches
deep and 10 to 12 inches apart in the ridges. The harvest com-
mences when the parts above ground are withering, which requires
9 to 11 months.
Properties. Oil of ginger, distilled by Haensel 2 had the fol-
lowing properties: dis” = 0.8705; ap (in 20 p. c. alcoholic solution
in 50 mm. tube) = —4.14°; saponification number 13.5; 1 part of
oil is soluble in about 65 parts of 80 p. c. alcohol.
OILS OF THE PIPERACEAE.
81. Pepper Oil from Long Pepper. G.-H-K., p. 322.
Wangerin obtained 0.9 p. c. of volatile oil from long pepper,
by steam distillation. The sp. gr. of the oil was 0.8841; b. p. 264°
to 280°. It was laevo-rotatory, and was free from aldehydes.
83a. Oil from Piper Famechoni.
Barillé” obtained 4.47 p. c. of volatile oil from the fruit of Piper
Famerhoni, Heckel, the Kissi-pepper from Upper-Guinea.
86. Matico oil. G.-H...-K., p. 335.
Properties and Composition. According to Thoms 8 the
Matico oils of commerce differ widely in their composition. An oil
examined by him had a yellowish green color and an order of Ma-
tico. Sp. gr. 1.1343 at 16° C. 46 p. c. of the oil distilled from
282–286°.
The oil contained dill-apiol, which when heated with alcoholic
potassa was changed to iso-apiol, m. p. 56; small quantities of
parsley-apiol, m. p. 30°; a hydrocarbon, b. p. 121–130 at 13 mm.
2 Haensel’s Ber. 1904 (4), p. 15.
1 Pharm. Journ. 73, p. 958
2 Pharm. Centralh. 45, p. ií4.
3 Arch. d. Pharm. 242, p. 328.
PIPERACEAE. 15
which solidified at –18°; a phenol ether which yielded a crystalline
bromine derivative m. p. 123–124°. Matico camphor and asa-
ron, which are supposed to be normal constituents of Matico oil,
were not found in this oil.
From true Matico oil distilled from the leaves of Piper angusti-
folium. Ruiz et Pav., Thoms 4 obtained crystals of asaron, m. p.
60–61°, which separated out from the oil upon standing. After
filtering off the crystals of asaron, the oil had a sp. gr. of 0.930 at
18° C. and was slightly laevogyrate (–0.3° at 18° C. in 100 mm.
tube). In a fraction of the oil, distilling from 70–71° at 13 mm.,
cineol was identified (cineolic acid, m. p. 196.5°). Neither dill-apiol
nor parsley-apiol, which had been isolated from a commercial Matico
oil, could be identified in this oil. This difference in the composition
of Matico oils, may be attributed to the use of different varieties of
Piper angustifolium, in the distillation. The assumption may also
be made that the leaves of Piper angustifolium collected in one
season of the year, may yield an oil containing apiol, while those
collected during another season may yield an oil containing only
asarone. This is partly substantiated by the similarity of these com-
pounds as shown by their structural formulas-
CH=CH-CH3 CH2—CH=CH2
/ N / N
/ NO.CH3 / NO.CH3
| |
CH3ON / CH3O N /O
N / N /
OCH3 O—CH2
Asarone. Parsley-apiol.
CH2—OH=CH
/N
chor N
| |
CH3. ON /()
N/
O—CH2
Dill-apiol
4 Apoth. Ztg. 19, p. 771,
16 TIIIE VOLATILE OILs.
&
OILS OF THE BETULACEAE.
96 a. Oil of Betula alba.
Haensell has obtained 0.049 p. c. of an olive green oil from the
leaves of Betula alba. The oil becomes semi-solid at room tempera-
ture, becoming liquid again at 35° C. Sp. gr. at 35° C. = 0.9074.
It is optically inactive. Acid number 99; , saponification number
146.7. The oil freed from the crystalline mass, has a sp. gr. of
0.8723 at 20°, but otherwise has the same properties as the original
oil.
OILS OF THE SANTALACEAE.
99. Sandalwood Oil. G.-H...-K., p. 338.
Properties. . According to Parry and Bennett I the index of
refraction of pure sandal wood oil should never fall below 1,5030
and when distilled into fractions of 10 p. c. each under reduced
pressure, no fraction should have an index of refraction of less than
1.5000 and the optical rotations should only vary within very
narrow limits. They have also determined the following constants of
acetylized oils:
(115° = 0.986 to 0.9885.
a p = —13° 50' to — 14° 30'.
Np 20° = 1.4894 to 1.4916.
From the examination of a large number of East Indian sandal-
wood oils, Seidler” found true oil to have the following properties:
The oils were of a very light yellow color and had a mild sandal-
wood Odor, reminding somewhat of cautchouc. All colored oils should
be discarded. Sp. gr. at 15° C. between 0.975 and 0.978. New oils
had optical rotation of –17° to —18.2°. Two oils had ap = –15.20
and 16.3°. The oils were soluble in 4–5 parts of 70 p. c. alcohol.
Acid number of new oils 0.28–2.8. Two old oils had acid number
of 6. Saponification number of fresh oils 1.68–7.28; old oils 12.88.
One gram of acetylized oil required from 197.86 to 209.06 milli-
grams of KOH for Saponification. Boiling point of the oils was
between 299–305° at 760 mm.
Adulteration. According to Seidler” sandalwood oil is adulter-
ated with alcohol, fatty oils, cedar wood oil, gurjun balsam oil, and
copaiva balsam Oil.
1 Haensel's Ber. 1904 (3), p.
7.
1 Chem. and Drugg. 64, p. 202.
2 Apoth. Ztg. 19, p. 795.
SANTALACEAE. 17
Two oils occurring in the market in capsules, were found by
Runge 8 to be highly adulterated as is shown by the following con-
stants: dis? = 0.959; ap = +6° 30'; santalol content 56.5 p. c.
Insoluble in 10 parts of 70 p. c. alcohol.
103. African Sandalwood Oil. G.-H...-K., p. 345.
Properties. African Sandal-wood oil, according to Seidler,4
has the following properties:
Sp. gr. = 0.934—0.941.
ap = —37.2° to —39°.
Saponification number 0.56–2.24.
The oil has a light green color, and is insoluble in 70 p. c. alco-
hol, but soluble in 20 parts of 90 p. c. alcohol.
OILS OF THE ANONACEAE.
118, 119. Ylang-Ylang Oil and Cananga Oil.
G.-H...-K, p. 362.
Source and Prep a ration. According to Flacourt 1 both
Unona latifolia and Unona odorata which have for a long time
been grown as trees for avenues, are used for the production of
ylang-ylang oil in Réunion. In order to grow the trees from seed,
the latter are placed in a seed-bed and when the young plants are
1 to 1% months old, they are planted in nurseries which must be
situated in the shade. This planting out in nurseries is in Réunion
generally preceeded by a process in which the young grown plants
are placed singly in beaker-formed vessels, called ‘tentes’ which are
made from the leaves of Pandanus utilis. After another two months
the plants are transferred to the plantation and for the next two
years must be tended very carefully. After the third year the trees
begin to flower, and by cutting back the tops, the yield of flowers is
greatly increased.
The flowers are collected from May to August, and the fresher
the flowers are when distilled the better is the quality of oil ob-
tained. 50 to 64 kilos of fresh blossoms yield about 1 kilo of oil,
i. e. 1.56 to 2 p. c. --
Among the products of economic value in the Philippines, ylang-
ylang oil as an export amounted to $123,182 in 1903? 75 pounds
S LOC. Cit.
4 Apoth. Ztg. 19, p. 797.
1 Revue de cultures, col. 13, p. 366; 14, p. 16.
2 Monthly Summary — p. —; J. Soc. Chem. Ind., 23, p, 918,
18 THE WOLATILE OILs.
of flowers worth from 8 to 15 cents gold per pound, yield one pound
of oil. The cost of manufacture is about $4 and it sells readily for
$40–$55.
Properties of Can a nga Oil. Schimmel & Co. 8 have
examined a sample of cananga oil received from Bangkok, which
had been distilled from the fresh and dried blossoms of cultivated
cananga trees. The oil had the folowing properties: dis” = 0.9200;
ap = — 51° 40' ; acid number 1.82; ester number = 34.17. The oil
was insoluble in 10 volumes of 90 p. c. alcohol, but was soluble in
0.5 volume of 95 p. c. alcohol, the solution, however, becoming
turbid upon the addition of more alcohol.
OILS OF THE MYRISTICACEAE.
121. Oil of Nutmeg. G.-H...-K., p. 366.
Source. In the cultivation of nutmeg trees only fresh seed can
be used as the seed, according to Gillavry 1 rapidly loses its ger-
minating power. A month after sowing, the seed germinates, but
the young plants must not be taken up until after 18 months, and
then only together with a large lump of soil. The plants should
grow in a shady place until the trees have developed a sufficient
number of branches to shade the soil themselves. The trees bear
fruit from the seventh year, but the crop is not good until the
twelfth year, and then improves from year to year.
The preparation of the crop is very simple. The fruit-pods and
mace are removed from the seed, washed in salt water and dried as
quickly as possible in the sun or in a drying cupboard. The nuts
from which the pods have been removed are rolled in slaked
lime and packed in cases for shipment.
Properties. An oil distilled by Schimmel & Co., 2 distilled
from a good quality of nutmegs, had a specific gravity of 0.9220 at
15° and ap = + 7° 52'. Soluble in 0.5 volume of 90 p. c. alcohol.
This oil has a higher sp. gr., a smaller angle of rotation and is
soluble in a less amount of 90 p. c. alcohol than most commercial
nutmeg oils, which are usually obtained from light worm-eaten nuts.
These latter oils, contain more terpenes, while the other oil contains
more oxygenated constituents.
3 S. & Co. Itep. April–May, 1904, p. 18.
1 Revue des, cultures coloniales, 1904, p. 34.2.
2 S. & Co. Itep. Oct.–Nov., 1904, p. 65.
LAURACEAE. 19
OILS OF THE MONIMIACEAE.
122. Oil of Boldo Leaves. G.-H...-K., p. 368.
Properties. From 12 kilos of dry boldo leaves, Tardy * ob-
tained 200 gms. of a volatile oil, corresponding to a yield of 1% p. c.
It had a sp. gr. of 0.876 and ap = —6°30'.
Composition. The oil contains a phenol, probably eugenol,
cumic aldehyde, pinene and an oxygenated body, C10H18O. The
higher boiling fractions contain a laevorotatory sesquiterpene.
OILS OF THE LAURACEAE.
128. Oil of Camphor. G.-H...-K., p. 370.
Source. The camphor trees in Japan are best grown from seed
which is collected in the autumn 1 and which, after being dried, is
kept during the winter in white sand. Before sowing, the seed is
soaked in water for 24 to 48 hours. When the plants are 10 to 16
inches high, they are transplanted. The space between the plants
varies, according to whether it is desired to obtain the camphor
from the leaves or wood of the tree.
According to Shirasawa? the oil cells in the young plant con-
tain an ethereal oil, but the transformation of the oil into camphor
does not take place for some time after the formation of the oil.
Composition. Schimmel & Co. 8 have identified borneo) in oil
of camphor. A fraction of oil, b. p. 210°–222°, was treated with
phthalic acid anhydride, and the resulting mixture was neutralized,
shaken with ether, and then saponified. The borneol obtained
crystallized from petroleum ether melted at 203°.
129. Oil of (Ceylon) Cinnamon. G.-H...-K., p. 377.
Adulteration and Examination. Pauchaud 4 recommends
the following modification of the bisulphite method for the assay of
cinnamic aldehyde:
To exactly 10 grams of oil contained in an Erlenmeyer flask of 150 c. c.
capacity, 20 c. c. of a 30 p. c. sodium bisulphite solution are added. The
flask is heated on a water bath until the yellow mass first formed is entirely
dissolved, and then 40 c. c. more of the sulphite solution are gradually
* Journ. de Pharm., 1904, p. 132.
1 Communications from the Biolog. agric. Inst, at Amani 1904 : S. & Co. Rep.
Oct.–Nov. 1904, p. 15.
2 Bull. Coll. of Agric., Tokio, p. — : Proc. A. Ph. A., 52, p. 847.
8 S. & Co. Rep. April–May, 1904, p. 17.
4 Schweiz. Wochensch F. f. Ph., 42, p. 126.
20 THE Wol ATILE OILs.
added. After cooling, the liquid is transferred to a separatory funnel, the
flask being twice washed out with 10 c. c. of ether. 10 c. c. more of ether
are added, and the whole shaken thoroughly. The aqueous layer is shaken
with an additional 20 c. c. of ether, and the combined ethereal solutions
evaporated in a tared flask, and the residue dried at 95—100° for 9% of an
hour. The weight of residue subtracted from 10 gives the weight of cinna-
mic aldehyde.
Harms 5 recommends the following method of assay:
From 0.5 to 2 grams of the oil, are emulsified with 85 c. c. of water
and 0.25 to 0.35 grams of semi-oxamazide, dissolved in 15 c. c. of hot
water, added. The mixture is occasionally shaken for three hours. The
precipitated cinnamic aldehyde semi-oxamazone, C11H11N3O2, is collected on
a tared Gooch filter, washed with cold water, dried for 4 to 5 hours at
105° C., and weighed. The weight of semi-oxamazone multiplied by 0.6083,
gives the amount of cinnamic aldehyde present.
The assay is based on the following reaction:
CONH-NH2 CONH-N=CH-CH=CH-Cahs
| + C8H17—CHO = t
CONH2 ONH2 + H2O.
Billon 9 recommends a color reaction with sodium or potassium
arsenite, to distinguish between Ceylon oil and Cassia oil. Schimmel
& Co., 7 however, declare this test worthless.
According to Schimmel & Co. 8 the adulterants of Ceylon oil
most commonly used, are oil of cinnamon leaves, cassia oil, and
pure cinnamic aldehyde. These can usually be detected by the deter-
mination of the aldehyde content, which should be between 70 and
75 percent. The addition of oil of cinnamon leaves, diminishes the
content of cinnamic aldehyde, and raises the eugenol content. Cassia
oil and cinnamic aldehyde raise the aldehyde content.
132. Oil of Cassia. G.-H...-K., p. 382.
Composition. The odorous substance called ‘farnesol' which
is a sesquiterpene alcohol, isolated from the oil of ambrette seeds,
occurs also in cassia oil. 9
Adulteration. Schimmel & Co. 10 have repeatedly observed
6 Pharm. Centralh. 45, p. 37.
6 Pharm. Ztg., 49, p. 107.
7 S. & Co. Rep. April–May, 1904, p. 22.
8 S. & Co., Rep., April–May, 1904, p. 26.
9 Chem. Ztg., 1904, p. 307.
0 S. & Co., Rep., April–May, 1904, p. 19,
LAURACEAE. 21
that cassia oil from China is adulterated with small quantities of
colophonium. This was readily noticable by the larger distillation
residue (above 11 p. c.) as well as the higher acid number. With
oils so adulterated, a precipitate is formed when a saturated alcoholic
solution of lead acetate, is added to the alcoholic solution of the oil
(1 in 3), whereas in the case of pure oil no precipitate is formed.
133. Japanese Cinnamon Oil. G.-H...-K., p. 391.
Source. Japanese oil of cinnamon is obtained from the leaves
and young twigs of Cinnamomum Laurenii, and in Japan is called
Oil of Nikkei. The nikkei tree is found in the hottest parts of Japan.
The oil is obtained in a yield of about 2 p. c.
Properties and Composition. The oil has a bright yellow
color and has an odor reminding of citral and Ceylon cinnamon oil.
An oil examined by Schimmel & Co. 11 had the following constants:
d15° = 0.9005; ap = —8° 45'; acid number 3.01; ester number 18.6;
soluble in 2.5 volumes of 70 p. c. alcohol, with opalescence, and 1
volume of 80 p. c. alcohol. The oil contains 27 p. c. of aldehyde,
chiefly citral (a-citral-3-naphthocinchoninic acid m. p. 199°); cineol
and linalool, the latter to the extent of 40 p. c. The oil contained
no cinnamic aldehyde.
149. Oil of Laurel Leaves. G.-H...-K., p. 402.
Properties. Oil of laurel leaves is described by Thoms &
Molle12 as having a light yellow color, a strong but pleasant aro-
matic odor, a sharp bitter taste and an acid reaction. Sp. gr. =
0.9257 at 17°; ap = — 15.95°; saponification number 49.84; acid
rfumber 2.74; ester number 47.10.
Composition. The oil contains acetic, isobutyric, and Valeria-
nic acids, free and combined. Capronic acid as ester was also identi-
fied. Eugenol, b. p. 247, (benzoyl derivative m. p. 70.5) to the extent
of 1.7 p. c., cineol, 50 p. c.; geraniol (diphenylurethane m. p. 83°).
Pinene was also identified, and the higher fractions of the oil un-
doubtedly contains sesquiterpenes and sesquiterpene alcohols.
According to Haensel 18 the terpene part of laurel leaf oil, con-
sists almost entirely of l-pinene (ap = —36°11'; pinene-nitrolbenzyl-
amine m. p. 122). Small quantities of phellandrene are also present.
; i.º. ººººººººº, p. 99. &
12 Arch. d. Pharm., 242, p. 1
1s Haensel’s Ber., 1904 (1), p. 16.
22 THE WOLATILE OILs.
151. Kuro-moji Oil. G.-H...-K., p. 404.
Properties. According to Schimmel & Co., the oil has a pale-
yellow color and the following constants: dis? = 0.8947; ad =
— 14° 29’; ester number 29.87; soluble in 0.9 volume of 80 p. c.
alcohol.
Composition. The oil contained cineol, identified by the iodol-
compound and probably also linalool.
152. Mountain Laurel Oil. G.-H...-K., p. 404.
Properties. The oil of the Californian Laurel is described by
Power and Lees 14 as pale-yellow, having at first an agreeable aro-
matic and somewhat camphoraceous odor, but when strongly in-
haled exceedingly pungent. Sp. 0.9483 at 16°; an = —22°. Soluble
in 1.5 parts of 70 p. c. alcohol.
Composition. The oil contains small amounts of formic acid
and a mixture of higher fatty acids; eugenol (benzoyl derivative
m. p. 70°) and eugenol methyl ether (bromo-eugenol methyl ether
dibromide, m. p. 78°–79°); l-pinene (nitrolbenzylamine m. p. 124–
125°); about 20 p. c. of cineol (tetraiodopyrrole derivative m. p.
115°). The bulk of the oil about 60 p. c. consists of a ketone,
C10H140, called umbellulone. Its semicarbazidosemicarbazone melts
at 217°. The pure umbellulone, regenerated from this derivative is
a colorless liquid, having the characteristic odor of the original oil.
B. p. = 219–220°; sp. gr. 0.9581 at 15°; an = –37°. The oil also
contains small quantities of safrol.
OILS OF THE CRUCIFERAE.
161. Oil of Mustard. G.-H...-K., p. 409.
Estimation. According to Firbas 1 in the quantitative estima-
tion of oil of mustard as given in the German Pharmacopoeia, the de-
composition of the thiosinamine silver compound is not completed
within 24 hours in the cold. By applying heat, values were obtained
with this method which were higher in proportion to the time during
which the mixture was heated. The increase in values, however, may
by partly due to the carbon disulphide and other constituents of
mustard oil, which are decomposable at a higher temperature or
prolonged heat.
14 Journ. Chem. Soc., 85, p. 629.
1 ApOth. Ztg. 19, p. 53.
RESEDACEAE AND ROSACEAE. 23
Vuillemin 2 recommends the following modification of Dieterich's
estimation of oil of mustard in mustard seed:
5 grams of the finely powdered mustard seed are placed in a 200 c. c.
round-bottom flask, containing 100 c. c. of water at 30°C. The well closed
flask is allowed to stand for an hour, with frequent agitation. 20 c. c. of
alcohol are then added, the flask connected with a condenser. One half of
the liquid is distilled over, the vapors being passed through the condensei' into
an Erlenmeyer flask containing 30 c. c. of ammonia and 10 c. c. of alcohol.
This flask should be connected with a second one to prevent any loss. The
condenser is rinsed with water, the distillate mixed with a few c. c. of
silver nitrate solution (1:10) and the mixture heated on a water bath until
the silver sulphide is entirely settled and the supernatant liquid is perfectly
white. The precipitate is filtered off, washed with hot water, alcohol and
ether, and dried at 80° C. until of constant weight. The weight of silver
sulphide multiplied by 8.602, gives the percent of oil in the seed.
Properties. According to Liebreich 8 the action of mustard in
the process of digestion is almost exclusively due to the oil, which
in small quantities acts as a bactericide, without, however, disturb-
ing the functions of the digestive ferments. In addition, mustard
produces an increased secretion of the gastric juice because of the
irritating action of the oil of mustard.
OILS OF THE RESEDACEAE.
165. Oil from Mignonette Flowers. G.-H...-K., p. 418.
By distilling the petroleum ether extract of Reseda flowers with
steam, Soden i obtained 0.003 p. c. of a yellow volatile oil, possess-
ing an intense mignonette odor and becoming solid in the cold.
Sp. gr. at 15° = 0.961; an at 17° = + 31° 20'; acid number 16;
ester number 85. When treated with caustic potash an odor of
ammonia is produced. The oil contains aldehydes.
OILS OF THE ROSACEAE.
171. Oil (Otto) of Rose. G.-H...-K., p. 423.
Production. In the rose region of Bulgaria, a hektar (about
2 acres) of land produces about 3000 kilograms of rose petals, from
which one kilogram of oil is obtained. The distillation is carried on in
retorts, each retort holding 10 kilograms of flowers and 75 liters of
Water.
2 Apoth. Ztg., 19, p. 607.
3 Therap. Monatshefte, 18, p. 65.
1 Journ. f. prakt. Chem., (2) 69, p. 256.
1 Pharm. Post, 1904, p. 77.
24 THE WOLATILE OILs.
As soon as the water is brought to boiling, the heat is removed
and the temperature gradually lowered, until no more distillate
comes over. The bulk of the distillate, therefore, comes over without
boiling the liquid in the retort. The heating and gradually cooling
is repeated until 12 liters of distillate are obtained. The aqueous
liquid is distilled a second time.
According to Jeancard and Satie 2 1000 kilograms of flowers
yield 300 grams of oil, when the distillate is cohobated but only
60–70 grams if the liquid is not cohobated. -
Properties. From the results of numerous analyses, S. & Co.8
give the following constants for Bulgarian oil of rose:
Specific gravity at 80°/15° 0.849 to 0.885,
Angle of rotation — 1930' to —3°,
Index of refraction at 25° 1.452 to 1.464,
Congealing point + 19° to + 23.5°,
Acid number 0.5 to 3,
Ester number 8 to 16,
Total geraniol content (geraniol plus citronellol) 66 to 74 p. e.,
Citronello! content 26 to 37 p. c.
The citronellol content of oil of rose is determined by formyliza-
tion, that is 1 volume of oil is heated with 2 volumes of 100 p. c.
formic acid, for One hour in a flask connected with a reflux condenser.
The rest of the method is the same as in acetylization.
Jeancard and Satie 4 have examined an oil distilled from the
blossoms after having removed the petals. The oil had the following
properties: sp. gr. at 15° = 0.8704; ap = −41°; solidifying point
+ 8°; acid number 6.12; ester number 22.4; the oil contained 51.13
p. c. of stearoptene, m. p. 14° and 13.56 p. c. of citronellol, but no
geraniol.
Soden and Treff" have isolated from rose oil the terpene-alcohol
nerol, C10H18O. The compound is present to the extent of from 5
to 10 p. c. and has the following properties:–sp. gr. at 15°= 0.8814;
b. p. at 736 mm., = 224°–225°; at 25 mm. = 125°; absorbs 4
atoms of bromine; m. p. of diphenylurethane derivative, 52–539.
The aroma of rose oil is in part due to the presence of this com-
2 Bull. Soc. Chim., (3) 31, p. 934.
8 S. & Co. Rep. Oct.–Nov., 1904, p. 81,
4 Bull. Soc. Chim., (3) 31, p. 934.
5 Berichte, 37, p. 1094,
ROSACEAE. 25
pound. If a small quantity of nerol be added to a mixture of arti-
fically prepared geraniol and citronellal, the liquid acquires the
characteristic rose odor.
Oil of rose was also found to contain 1 p. c. of eugenol (eugeno!
benzoate, m. p. 69°–70°) and about 1 p. c. of a sesquiterpene
alcohol, C15H26O which is probably identical with that from acacia
flower oil. It is a thick colorless oil, optically inactive, b. p. at 4
mm., 149°, has a pleasant cedar wood like odor and absorbs 6
atoms of bromine.
By extracting French rose petals with petroleum ether, and
distilling the residue after evaporating the petroleum ether, with
steam, Soden 6 obtained 0.052 p. c. of oil. The oil had a sp. gr. Of
0.967 at 15°; an at 17° = –1° 55' ; congealing point 5° to 7°;
ester number 4.6. By means of phthalic acid anhydride, 75–80 p. c.
of the oil was found to consist of alcohols, principally phenyl-ethyl-
alcohol.
From German rose petals, 0.0107 p. c. of oil was obtained, sp.
gr. at 19° = + 0°9'; congealing point + 12; acid number 3; ester
number 4.
Examin a tio n. Cox and Simmons 7 recommend the determina-
tion of the iodine number to test the purity of rose oils. The method
is as follows:
0.1 to 0.2 grams of the oil are diluted with 10 c. c. of alcohol or chloro-
form, 25 c. c. of Hübl’s iodine solution added and the mixture allowed to
stand at room temperature for 3 hours. The Hübl’s solution must be
freshly prepared and the iodine titration carried out as quickly as possible.
The iodine number of pure oils lies between 187 and 194, while
that of adulterated oils is always well over 200,
Jeancard and Satie 8 are of the opinion that the congealing point
of rose oil is no criterion of its stearoptene content. An oil from
tea rose, contained 72–74 p. c. of stearoptene and congealed at 23.5°,
whereas a much higher congealing point was to be expected.
172. Oil of Bitter Almond. G.-H...-K., p. 436.
The results of the analyses of several samples of almond, apricot
kernel and peach kernel oils, by Lewkowitsch 9 show that these oils
can not be distinguished from each other by means of chemical or
6 Journ. f. prakt. Chem., (2) 69, p. 256.
7 Pharm. Journ., 72, p. 861.
8 Bull. Soc, Chim., (3) 31, p. 934.
9 Analyst, 29, p. 105.
2(3 THE WOLATILE OILs: 1904.
physical constants. If 5 parts of the oil are treated with 1 part o
a mixture of equal parts by weight of sulphuric acid, funning nitric
acid and water, pure almond oil does not change color whilst peach
kernel oil assumes a peach-blossom tint.
174 a. Oil from Geum urbanum.
According to Bourquelot and Herissy, 10 the fresh plant Geum
urbanum, bruised and macerated for 12 hours, yields a small quantity
of an essential oil containing eugenol. The oil does not exist as such
in the plant, but is produced by the action of a ferment on a gluco-
side. The alcoholic extract of the root is odorless, but if a ferment
is introduced, an odor of oil of cloves is at once produced.
174, b. Oil of Raspberry.
A greenish oil was distilled by Haensel 11 from the press mark of
raspberries which possessed in a marked degree the odor of the fer-
mented berries and may, therefore. be a product of fermentation
rather than a constituent of the normal fruit.
It is soluble in 30 parts of 80 p. c alcohol.
D** = 0.8833, an = — 2.8°, saponification number 193, S.N.
after acetylization = 215.
OILS OF THE LEGUMINOSAE.
175. Oil of Copaiba. G.-H...-K., p. 445.
Prep a ration. Itallie and Nieuwland I obtained an oil from
the Surinam copaiva, derived from Copaifera guinnensis. The oleo-
resin was dissolved in ether and the solution shaken with a 5 p. c.
solution of sodium carbonate to remove resin acids. The neutral
ethereal Solution was then distilled with steam.
* Properties. The oil is a thick, clear liquid, colorless at first
but gradually becoming yellow. Sp. gr. at 15° = 0.9052; an at
15° = −10° 13. 75 p. c. of the oil boils from 254–270° the fraction
having a sp. gr. = 0.9007; a p = — 11° 50'.
Con position. The oil contains no caryophyllene as does
Copaiva oil from other sources. Fraction 254°–270°, contains two
10 Journ de Pharm , ((3) 18, p. 364).
** Bericht y. II. Haensel iiber ºl. 3. Vierteljahr 1904, 1). l ;3
1 Arch. (l. Pharm., 242, p. 539, *
LEGUMINOSAE. 27
sesquiterpenes, one of which is laevo- and the other dextro-rotatory.
ladinene is also present in small amounts in fraction 270–280°, and
a sesquiterpene alcohol, m. p. 112–115°.
182 a. Oil from Amorpha fruticosa.
Origin. Pavesi 2 isolated from the fruits of Amorpha fruticosa,
L., 1.5–3.5 p. c. of an essential oil. The leaves yield 0.5–0.8 p. c.
of Oil.
Properties. These oils are yellow and have a bitter taste and
congeal at about — 17°. The following constants were observed :
Oil from green fruit: sp. gr. at 15° = 0.9919
np at 17° == 1.49951
Oil from ripe fruit: sp. gr. at 15° = 0.9057
In p at 17° = 1.500.36
np at 17° of oil from leaves, 1.50083–1, 50928.
Composition. The oil from the fruits consists almost entirely
of hydrocarbons. The oils from fruits and leaves contain cadinene
(hydrochloride m. p. 117°) and another sesquiterpene, called a mor-
phene, which is possibly identical with clovene.
182 b. Oil of Cassia Flowers.
Origin. The Acacia farmesiana, Willd., which yields the oil of
cassia-blossoms, examined by S. & Co., 3 grows also in Cuba,” where
it is called Aroma francesa, in such quantities, that it has become a
veritable plague in some parts of this island. Aside from the blos-
soms, which can be used to prepare the oil, the wood can be used
for furniture, and the bark for the preparation of tannin.
Properties. The commercial Indian cassia bud pomade, yielded
0.171 p. c. of a bright yellow oil, having a strong, pleasant cassie
odor. Sp. gr. at 15° = 1.0475; ap = = 0°; no at 20° = 1.5133;
saponification number 176.
Soden 5 obtained 0.084 p. c. of oil, by extracting the flowers
with petroleum ether, and distilling the residue with steam. Sp. gr.
at 27° = 1.040; an at 25° = –0°40'; congealing point 18°–19°;
acid number 425; ester number 114, corresponding to 30.9 p. c. of
methyl salicylate. tº
Estr. aus. Rend. del IR. Ist I, omb. di Sc. e lett, (2) 37, p. 487
S. & Co. Rep. A pril–May, 1904, p. 23.
Journ. (l'agricul. tropicale, 4, p. 334.
Journ. f. prakt. Chem., (2) 69, p. 256.
:
28 THE WOLATILE OILS : 1904.
Composition. S. & Co. isolated from cassia bud oil, methyl salicyl-
ate (b. p. 224°–226°); p-cresol, identified by oxidizing its methyl
ether to anisic acid, m. p. 180°. The lowest boiling fractions con-
tained benzaldehyde (semi-carbazide, m. p. 21.4°) and benzyl alcohol
(phthalic acid ester m. p. 105°–106°). The oil also contained anisic
aldehyde and a compound which yielded a semi-carbazone, m. p.
177°–178°. The compound had a characteristic menthone odor.
OILS OF THE GERANIACEAE.
183. Oil of Rose Geranium. (...-H...-K., p. 449.
() rigin and Prep a ration. According to Cordemoy 1 the cul-
tivation of Pelaigonium capitatum, Ait., for the production of oil of
geranium, is carried on at Réunion at altitudes of 1300 to 1400 feet.
At a higher elevation the plants do not thrive. About 250 stills are
in operation in this colony. A kilogram of oil is obtained from 700
to 1000 kilograms of leaves and the fresh oil has a green color. The
leaves, after distillation are used as manure for potatoes.
('O m position. In the low boiling fractions of geranium oil,
S. & Co. 2 have identified amyl alcohol (phenyl urethane m. p. 41°
to 43°); pinene (nitrosochloride, m. p. 102°; nitrol benzylamine,
m. p. 122°–123°); phelland rene (impure nitrite, m. p. 114°–115°);
linalool (phenyl urethane, m. p. 65°–66°). w
Jeancard and Satic 3 have studied the effect of woather-conditions
on the constitution of geranium oil, Pelº Igonium odoratissimum.
('old nights decrease the alcohol content, without, however, increas-
ing the ester content, and lower the percentage yield. The geraniol
content remains fairly constant, while the citronellol content increases
with the greater yield of oil. Sp. gr. varied from 0.8968 to ().89%)()
and up from — 8.5° to —9.44°.
Exam in a tion. Duyk 4 recommends the following test to
characterize volatile oils:
In a small test-tube of about 15 c. c. capacity, 4 c. c. of liquid paraffin
are placed, then 1 c. c. of the oil to be tested and the whole thoroughly
mixed. 2 c. c. of pure sulphuric acid are carefully added so that, the acid
will form a layer on the bottom. The tube is then quickly closed with a
1 IRevue des c 11tures coloniales, 14, p. 1 7 ().
2 S. & Co. Rep., April May, 1904, p. 55.
3 Bull. Soc. (him., (3) 3 ſ, p. 43.
* les Corps gras industriels, 31, p. 7 ().
Chem. ('entrallyl., 7.5 Il , p. 1:349.
Erythroxy LACE.E AND RUTACE.E. 29)
cork containing a thermometer. The initial temperature and the maximum
temperature reached when the liquids are mixed, is noted. The increase in
temperature iminus 1° (the rise caused by 4 c. c. of paraffin and 2 c. c. of
H2SO4) is a constant for pure oils.
For geranium oil the constant is 24°–25°. For the constants
of other oils compare the original.
OILS OF THE ERYTHROXYLACEAE.
186 a. Oil from Erythroxylon monogynum.
S. & Co.1 obtained from the wood of Erythroxylon monogynum
IRoxb., 2.56 p. c. of a volatile oil. The oil was a sticky crystalline
mass with a pleasant odor like that of oil from guaiac wood. Sp. gr.
is less than 1; melting point 42°–45°; acid number 6.77; ester number
1.56; ester number after acetylization 131. Soluble in one or more
volumes of 90 p. e. alcohol.
The crystalline substance in the oil, recrystallized from petroleum
ether melted at 11.7°–118°; an of a 13 p. c. chloroform solution =
+ 32° 28′. Upon analysis, it was found to have the formula (20 H32O
and is an alcohol yielding an acetate of the melting point 72°–73°.
OILS. OF THE RUTACEAE.
191. Oil of Buchu Leaves. G.-H...-K., p. 457.
According to Sage 1 the leaves of Diosma succulenta, var. Ber-
giana, called Karoo buchu, yield an oil by steam distillation which
is semi-solid at room temperature, and has a strong peppermint
like Odor. *
196. Oil of Lemon. G.-H...-K., p. 465.
Prep a ration. A machine for the mechanical preparation of
the oil was devised by R. G. Hunter,” Eng. Pat., 13, 171, June 10,
1904.
Composition. Schmidt 8 examined the so-called lemon camphor
or citrap tene. From the residues resulting from the manufacture of
lemon oil, colorless crystalline needles, m. p. 146°–147°C., were iso-
lated. They have the composition, C11 H 1004 and show a handsome
blue fluorescence in alcoholic solution. The substance contains two
methoxy groups, OCH3, and upon fusion with potassium hydrate
1 S. & ('o., Rep., April–May, 1904, p. 97.
1 Chemist & Drug., 65, pp. 506 and 717.
2 J. S. C. I., 23, p. 836.
3 Arch. d. Pharm., 242, p. 288.
:3() TILE WOLATILE (). LS : 1904.
yields phloroglucin and acetic acid. Citrap tene can therefore be re-
garded as dimethyl-aesculetin or dimethyl-daphnetin as shown by
the formulas:
('H ( II (IH CH
N / N Z \
('ll 30.0% N / CII nc/ N / (; H
| | |
- |
(HaO.C / N, /('-() ("I [3(). ('N / N /('E()
N / N / \ / N /
('H () (! II 3(). (' ()
dimethyl aesculetin. dimethyl-daphnetin.
While examining the most volatile terpenes from a very large
quantity of lemon oil Burgess and Page 4 obtained a fraction having
the following properties: — b. p. 123°–124° at 768 mm. ; sp. gr.
0.7275; [a] p = + 0; no = 1.4066 at 15°; mol. refraction 38.54,
By oxidation with potassium permanganate, butyric acid was ob-
tained. The authors, therefore, regard this hydrocarbon as octylene,
Cs H16. It is the lowest member of the olefinic series of hydrocarbons
hither to found in volatile oils.
Exam in a tion. Sadtler 5 recommends the following method for
the assay of lemon oil. The method is also applicable to other alde-
hyde-containing oils.
5 to 10 grams of the oil are weighed into an Erlenmeyer flask, and
after neutralization with s II ("), 25 to 30 c. c. ol a 20 percent, sodium sul-
phite solution are added. The sulphite solution is previously neutralized
with s HCl after being heated in a boiling water bath, rosolic acid being
used as indicator. The red color which forms in the aqueous layer, when
the Oil and sulphite solution are mixed, is discharged from time to time
With s IICI, the ſlask being heated and agitated repeatedly. When only a
|aint pink color remains, which is unešected by a few more drops of acid,
the number Ol C. c. Of N IICl solution used is noted. I'roun the citral factor
of . IICI, viz. 0.03802, the percentage of aldehyde can readily be calculated.
The method is explained by the following equation:
Co H15 CHO + 2 Na2SO3 + 2 H2O = (ºp H17 (NaSO3)2 (XIIO + 2 Na OII.
Kremers and Brandel" have adapted the cassia oil assay method
to the assay citral in lemon oil. The method is as follows:
4 Journ. Chem. Soc., 85, p. 1328.
5 Am. Journ. I’harm., 7 (5, p. 84.
6 I?harm. Iłev., 22, p. 15.
RUTACE.E. * 31
Transfer 5 c. c. of the oil with a pipette to a cassia flask, add 25 C. c.
of 80 p. c. sodium acid sulphite solution and place the flask in a water
bath at a temperatnre of 60° for 30 minutes, shaking the flask from time
to time. After allowing the flask and contents to cool completely, dilute .
gradually with distilled water, shaking well after each addition until the
flask is filled. The difference between the volume of the original oil and the
volume of residual oil, read off from the neck of the flask, is the aldehy, 'e
content of the oil.
According to Berté 7 even slight adulterations of lemon oil with
turpentine or lemon oil terpenes can be detected by distilling off 50
p. c. of the oil and comparing the optical rotations of the oil,
distillate and residue. In case of pure lemon oil, the rotatory power
of the distillate is slightly higher than that of the orignal oil, while
the rotation of the residue is lower. With adulterated oils the vari-
ations are entirely different, the rotation of the distillate being
generally lower than that of the original. oil.
Adulterations of lemon oil may be detected according to Harvey 8
by comparing the iodine absorption number of the oil with the ab-
sorption numbers for pinene and limonene.
197a. Oil from Sweet Orange Branches.
Roure-Bertrand Fils 9 obtained an oil from the branches of ('itrus
aurantium, Risso. The oil had a yellow color, sp. gr. at 15° =
0.8602; ap = + 56°46’; no at 20° = 1.472. It contained 4 p. c.
of citral (semicarbazone m. p. 16.3°); 4.1 p. c. of esters, calculated
for C10H170000Hs; and 19.7 p. c. of total alcohols, 12.7 p. c. being
geraniol (b. p. 110° at 10 mm. pressure). d-camphene (isoborneol,
m. p. 212°) and limonene (tetrabromide, m. p. 104°) were identified.
Linalool is probably also present.
199. Oil of Bergamot. G.-H...-K., p. 473.
Composition. In addition to the constituents of bergamot
oil already known, Burgess and Page 10 have detected pinene (hydro-
chloride, m. p. 103). A small quantity of a hydrocarbon, Cs H 16
previously found in oil of lemon (see Oil of Lemon), is probably also
present. The sesquiterpene limene (hydrochloride, m. p. 79) was also
identified.
7 Boll. Chim. Farm., 43, p. 34.9.
8 Journ. Soc. Chena, Ind., 23, p. 413.
9 IRoure-Bertrand Fils, Rep., Oct. 1904, p. 35.
10 Journ. Chem. Soc., S5, p. 1327.
32 TILE WOLATILE OILS : 1904.
In the lowest fractions of the bergamot Oil, acetic acid was iden-
tified. The acid, however, may not have been present in the oil as
such, but may have resulted from the hydrolysis of linalyl acetate.
201. Oil of Limette. G.-H...-K., p. 477.
Properties. Two limette oils, originating from Dominica,” one
obtained by expression and the other by distillation, had the follow-
ing properties: w
Hand-pressed. I)istilled.
Color...................................................... golden yellow bright yellow
Odor................. ..................................... lemon-like terebinthinate
Sp. gr. at 15°...................... ................. ().9008 ().8656
(/I) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . + 36°17' + 46°36'
op of first 10 p. c. of distillate............, + 39°30' + 53°8'
Acid number.......................................... 6.05 1.8
Ester number..................... •............ ..... 29. 55 4.05
Residue....….....................….. 17.8 p. c. 3.16 p. c.
The hand-pressed oil was soluble in 4 volumes of 90 p. c. alcohol
with a slight cloudiness and the distilled oil in 4.5 volumes.
Composition. According to Burgess and Page 1* terpeneless
or concentrated oil of distilled limes contains about 40 p. c. of free
alcohols. From fraction 100–105° at 17 in m. laevo-terpineol melt-
ing at 35° was isolated (nitrosochloride, m. p. 105°–106°; phenyl-
urethane, m. p. 111°).
From a second fraction, 130°–140° at 17 mm., consisting almost
entirely of hydrocarbons, a sesquiterpene hydrochloride, C15H24.3H(\l,
m. p. 79°, was obtained. The regenerated sesquiterpene, called
limene by the authors, had the following properties: b. p. 131° at
9 mm.; sp. gr. 0.873 at 15°; [0] p = +0; no = 1.4935 at 15° and
1.4910 at 19.5°; mol. refraction 68.2. It absorbs 6 atoms of
bromine. The hydrochloride is characterized by its remarkable power
of crystallization.
They also isolated a second terpineol (phenylurethane, m. p. 132°)
which possessed the peculiar odor of oil of limes,
205. Oil of Neroli. G.-H...-K., p. 480.
Prep a ration. According to Charabot and Laloue18 the formation
of oil in the orange tree proceeds most briskly in the young plant,
11 S. & C. Rep., Oet.—Nov. 1904, p. 54.
12 Journ. Chem. Soc , 85, p. 114.
13 (‘ompt. rend., 1:38, pp. 1228, 1513.
RUTACEAE. 33
the oil in the leaves having a smaller content of esters and alcohols
than the young twigs and stalks. As the plant develops, the leaf-oil
decreases pronouncedly in linalool content and increases slightly in
ester content. The oil from the twigs and stalks increases decidedly
in ester content, but decreases in total alcohol content.
The oil content of the blossoms decreases considerably during
the flowering period. As the buds develop, the content of esters of
terpene alcohols, methyl ester of anthranilic acid and total alcohols
increases. The geraniol content increases and the content of
linalool decreases. The oils from the different parts of the unfolded
flower do not differ very much, with the exception that the oil from
the petals contains a somewhat larger percent of the methyl ester
of anthranilic acid.
Properties and Composition. By extraction with petro-
leum ether, Soden 14 obtained 0.06 p. c. of oil from the orange
blossoms. Sp. gr. at 15° = 0.9245; ap = —2°30'; acid number 4;
ester number 102. The oil contained 6.9 p. c. of the ester of an-
thranilic acid.
Umney and Bennett 15 have examined an orange oil, obtained
from Buenos Ayres, whose exact source was unknown. It had a
sp. gr. of 0.887; ap = +2°. The oil contained 36.5 p. c. of linalyl
acetate, 38.4 p. c. of geraniol and 67.1 p. c. of total alcohols.
Although the oil had an exceptionally strong, pleasant odor, only
traces of methyl anthranilate were present. The oil probably also
contains pinene, dipentene, linalool and furfur aldehyde.
Examination. Freundler 16 recommends a reaction for the
detection and possibly also for the quantitative estimation of methyl
anthranilate in oils. Although no detailed directions are given, the
method depends upon the formation of thiophenyl ketotetrahydro-
Quinazoline when the methyl ester of anthranilic acid is heated with
phenyl mustard oil to 120°. The reaction takes place as follows:
CO—N–C6H5
/ N
/> /. / |
/ \c—cooCH, % NC/ + CH3OH
| + S=0=N–C6Hs=. CS
/C—NH2 / CN /
N/ N/ N /
NH
98 p. c. of the theoretical yield of quinazoline was obtained.
14 Journ. f. prakt. Chem., $º. p. 256,
15 Chem. and Drugg., 64, p. *ºf s
16 Bull. Soc. Chim., (3), 31, p. 882.
34 THE WOLATILE OILS : 1904.
OILS OF BURSERACEAE.
210. Oil of Opopanax. G.-H...-K., p. 488.
Properties. An oil distilled from the opopanax resin by
Schimmel & Co., I had the following constants: sp. gr. = 0.895;
ap = — 12°35'; saponification number 14.5; soluble in one volume
of 90 p. c. alcohol, the solution becoming cloudy upon the further
addition of alcohol.
Composition. The oil consists of a mixture of alcohols yield-
ing crystallizable phenylurethanes but none were characterized. It
also contained a sesquiterpene yielding a hydrochloride C15H24.3HCl,
m. p. 80°. The regenerated sesquiterpene had the following proper-
ties: sp. gr. at 15° = 0.8708; on = +0; no at 26° = 1.48873;
b. p. 114°–115° at 3 mm. The properties of this sesquiterpene as
well as its hydrochloride, agree closely with those of the sesquiter-
pene isolated from lime oil, called limene.
212. Oil of Elemi. G.-H...-K., p. 490.
An OleOresin, labeled (ºricari Elemi, obtained from the Brasilian
exhibit in Berlin in 1886, was examined by Tschirch and Reutter.2
It was a soft yellow-green mass, having a very pleasant, elemi and
lemon-like Odor.
By shaking an ethereal solution of the oleoresin with caustic
alkali and distilling the ether residue with steam, 3 p. c. of oil were
obtained. The oil was light yellow in color and had a combined
odor of turpentine, dill and lemon oils.
An OleOresin, 8 Tacºm.hacº Elemi, from the Philippines, of un-
known botanical origin yielded upon distillation with steam, 2 p. c.
of a light yellow Oil, which had a peculiar borneol-like odor. The
bulk of the oil distilled over from 170°–175°. The higher fractions
had a strong empyreumatic odor.
From a Tacamahac resin of commerce, Tschirch and Saal 4 ob-
tained 3 p. c. of oil.
H. Haensel 5 obtained 24.6 p. c. of a yellowish oil, sp. gr. 0.8907
at 20°: a = + 51.04°; sap. n. = 3, after acetylization = 71.5; Sol.
in 8.5 p. (by weight) of 80 p. c. (vol.) alcohol.
Bericht S. & Co., 1904 II, p. 69.
Arch. d. Pharm., 242, p. 117.
Arch. (l, Pharm., 242, p. 352.
Arch. d. Pharm. , 242. p. 395.
Bericht von H. H., 1904 III, p. 11.
Arch. d. Pharm., 242, p. 3-18.
:
BURSERACE.E, MALWACEE, VIOLACE.E. 35
Aº
212 a. Oil of Colophonia Elemi.
Colophonium Mauritiana (Canarium Mauritiana), a tree growing
on the island of Mauritius, yields large quantities of an oleoresin of
commercial importance. Tschirch and Saal 6 obtained 3 p. c. of a
volatile oil from the oleoresin which had a characteristic odor of dill,
fennel and lemon oils. The bulk of the oil distilled at 170–175°.
214. Oil of Linaloe. G.-H -K., p. 492.
An oil, examined by Schimmel & Co., 7 had the following con-
stants: sp. gr. = 0.8793; ap = + 7° 32'; acid number 1.02; ester
number 3.88; soluble in 1.7 vol. of 70 p. c. alcohol.
Laevorotation of not less than 5° is usually taken as a
distinctive sign of the purity of linaloe oil. This oil, however, is
dextro-rotatory and contains 65 p. c. of d-linalool (a|p = + 11°15').
In other respects it is normal.
OILS OF THE MALVACEAE.
224. Oil of Ambrette Seeds. G.-H...-K., p. 501.
By means of phthalic anhydride there was isolated from oil of
ambrette 1 a sesquiterpene alcohol, called farmesol, which had a sp.
gr. of 0.885 and a refractive index 1.4888.
225 a. Oil of Hypericum perforatum.
The entire herb of Hypericum perforatum yields upon steam
distillation 0.0928 p. c. of an olive green oil which has an acid
reaction and a strong peculiar odor. deo?= 0.8703; an of 50 p. c.
chloroform solution in 25 mm. tube = — 1.10°; acid number 23°:
saponification number 37. Insoluble in absolute alcohol. A small
quantity of a stearoptene separates out from the oil when exposed
to a low temperature.”
OILS OF THE VIOLACEAE.
229 a. Oil of Violet Flowers.
By extraction with petroleum ether, Soden I obtained 0.0031 p. c.
of a faintly greenish oil, which did not solidify in a freezing mixture.
The oil itself has only a feeble violet odor, which becomes prominent
7 S. & Co., Rep., Oct.–Nov., 1904, p. 5 (5.
1 Chem. Ztg., 1904, p. 307.
2 Haensel's Ber., 1904, 4, p. 16.
1 Journ. f. prakt. Chem., (2) 69, p. 256,
36 THE WOLATILE OILS : 1904.
upon dilution with alcohol, 1:10000. d.15° = 0.920; ap17° = +104°
15’; acid number 10; ester number 37. The cost of producing this
oil would be about 4000 pounds sterling per kilo.
Oil of Viola tricolor.
Desmouliere? has isolated methyl salicylate from the flowers of
Viola tricolor. The methyl salicylate does not exist in the plant as
such but in the form of a glucoside. An amorphous glucoside, which
is undoubtedly identical with gaultherin, was isolated. From the
fact that the odor of wintergreen oil is produced only by rubbing
the petals, it is concluded that the glucoside and ferment are found
in different cells of the plant and are only brought together by
rubbing.
OILS OF THE MYRTACEAE.
234. Oil of Pimenta. G.-H...-K., p. 509.
Properties. According to Pancoast 1 manufacturers of pimenta
Oil are compelled to modify their oils in order to make them conform
to the requirement of the U. S. P. 1890. The sp. gr. of 5 pure oils
varied from 1.025 to 1.040, considerably lower than the sp. gr. re-
quired by the U. S. P. 1890. The optical rotation of these oils
varied from — 19547 to — 6°43’.
A normal oil distilled by Schimmel & Co.2 had a sp. gr. 1.044
at 15°; a p = — 4° 30'.
CO m position. Schimmel & Co.8 have isolated from oil of
pimenta, cineol (cineolic acid, m. p. 202°); l-phellandrene, an =
–36° 36' (nitrite, m. p. 119°–120°); caryophyllene (nitrosate, m. p.
159°; nitrol piperidide, m. p. 146°–147°). The melting points of
the nitrosate, 148°–149° and of the nitrol piperidid, 1419–1439,
as usually given in literature are too low according to these authors.
Eugenol (benzoyl derivative, m. p. 69°) and methyl eugenol
(Veratric acid, m. p. 179–180°) were also identified. From the
distillation residue of the constituents soluble in alkali, palmitic acid,
m. p. 60°, was obtained.
2 Journ. Pharm. Chim., VI, 19, p. 12 1.
1 Merck's IRep., 1964, p. 157.
2 S. & Co. Rep., April–May, 1904, p. 76.
3 Ibidem.
MYRTACEAE. 37
235. Oil of Bay. G.-H...-K., p. 510.
Properties. From bay-leaves from Bermuda Schimmel & Co.8
obtained 1.33 p. c. of an oil having the following properties: sp. gr.
at 15° 1.0301; ap = — 3°4'; no at 20° = 1.53012. The oil con-
tained 61 p. c. of phenols and was soluble in 0.4 volumes of 80 p. c.
alcohol. It differs from the common bay oil, in having a higher
specific gravity and a much greater solubility.
Two samples of oil originating from Dominica had the following
properties:
1. Sp. gr. = 0.9500; phenol content 55 p. c.; soluble in 0.5
vol. of 90 p. c. alcohol.
2. Sp. gr. = 1.0298; phenol content 73 p. c.; soluble in 0.3
vol. of 90 p. c. alcohol, the solution becoming cloudy upon the
further addition of alcohol.
236, Oil of Cloves. G.-H...-K., p. 512.
Properties. Schimmel & Co. 4 obtained an oil from powdered
Amboina cloves, which had a much finer odor than ordinary clove
oil. Sp. gr. = 1.0456; ap = –1°24'; 78 p. c. of phenols. It formed
a clear solution with 1 vol. of 70 p. c. alcohol, becoming turbid
upon the further addition of alcohol, differing thus from ordinary
clove oil.
Exam in a tion. In consequence of the recognition of other con-
stituents in oil of cloves, Thoms 5 recommends the following modifi-
cation of his eugenol essay
5 gms. of the oil are heated on a water bath with 20 gms. of 15 p. c.
soda solution for half an hour. After complete separation of the hydro-
carbons, the aqueous layer, containing the eugenol, is separated and the
hydrocarbons washed twice with soda solution, the washings being added
to the eugenol solution. This is treated with 6 grams of benzoylchloride,
the reaction being completed on a water bath. When cool, the crystalline
mass is filtered off and transferred to a beaker with 50 c. c. of water. The
crystals are melted, agitated with the water and allowed to cool. This
washing with 50 c. c. of water is twice repeated. The crystalline mass is
then transferred to a beaker with 25 c. c. of 90 p. c. alcohol and warmed
until solution is effected. The solution is cooled to exactly 17°C, and the
crystals of benzoyl eugenol collected on a 9 c. m. tared filter paper.
The crystals are washed until the total filtrate measures 25 c. c. The paper
8 S. & Co. Rep., April–May, 1904, p. 13.
4. S. & Co. Rep., Oct.–Nov., 1904, p. 22,
5 Arch. d. Pharm., 241, p. 592.
38 THE WOLATILE OILS : 1904.
and benzoyl eugenol are transferred to a weighing flask, dried and weighed.
To the weight, of benzoyl eugenol thus obtained, ().55 grams are added, to
allow for the solubility of the eugenol compound in the 25 c. c. of alcohol
($1.2 (a + ().55)
l
} , in which a is the weight of benzoyl
used. From the formula
eugenol found, b the weight of the oil used, the percentage of eugenol can
be calculated.
According to Simmons 6 the refractive index of clove oil is directly
proportional to the eugenol content and therefore the oil can be
valued from its index of refraction. Oils having a eugenol content
of 83 to 93 p. c. had an index of refraction of 1.5297 to 1.5382.
238. Oil of Cajeput. G.-H...-K., p. 518.
Properties. Prinsen-Geerligs 7 believes that the fact that the
peculiar green color of cajeput oil, due to the presence of small quan-
tities of copper, can not be removed by shaking with water, must
be attributed to the presence of small quantities of butyric and
valeric acids which retain the copper in solution. If samples of caie-
put oil, free from acids and esters, to which have been added water,
and ethyl formate, acetate, or propionate, etc., are poured upon
copper turnings, only those oils containing butyrate or valerianate
acquire a green color which can not be removed with water.
Schimmel & Co.8 have examined three South Australian cajeput
oils whose exact, botanical source is unknown.
Cºnjeput oil, blanc. Sp. gr. = 0.8908; 0.0 - - - 8°8'; soluble in
0.5 volumes of 90 p. c. alcohol. The oil has a pepper-like odor and
probably contains cymene.
Cajeput oil, Vert. Sp. gr. = 0.8727; an = + 32°40'; soluble in
5 volumes of 90 p. c. alcohol. The oil had an odor of amyl alcohol
and contained cineol (iodol reaction).
(ajeput oil, larges feuilles. Sp. gr. = 0.8854; on = + 9° 7'
soluble in 2.5 volumes of 70 p. c. alcohol. The oil had a pale green
color and a very pleasant coriander-like odor.
248 a. Oil from Calyptranthes paniculata, Ruiz et Pº v.
e * , , 1. º 4 MQ." & & tº t ; : º
The oil from (alyptranthes Daniculatºv, Ruiz et Pº v., known in
Porto Rico as May () il, was examined by Schimmel & Co.9 The
6 (Shem. News, 90, p. 1-16.
7 Chem. Centralbl., 76, I, p. 95.
8 S. & Co. Rep., April–May, 1904, p. 97.
9 S. & Co. Itep., April–May, 1904, p. 95.
MYRTACEAE. 39
oil resembled lemongrass oil. Sp. gr. = 0.9509; ap = –1°52'.
Readily soluble in 80 p. c. alcohol, insoluble in 70 p. c. alcohol. It
contains 62.5 p. c. of citral.
249. Oil of Eucalyptus Globulus. G.-H...-K., p. 526.
Properties. Experiments inade by Hall 10 show that as an
antiseptic eucalyptol is inferior to all the other constituents of the
eucalyptus oils. The aldehyde aromadendral is the most active, next
piperitone and phelland rene.
The author also arrives at the conclusion that ozone is of very
considerable importance for the antibacterial power of eucalyptus
oil. Oils should be ozonised by allowing light and air to act upon
them.
According to Griffon 11 the draining action of the eucalyptus tree,
which has given it the name fever tree, must be attributed to the
property of producing an abundant foliage in a very short time.
Composition. Schimmel & Co.12 have isolated from the high
boiling fractions of the oil of Eucalyptus globulus, a sesquiterpene
alcohol, which crystallized in brillant needles, melting at 88.5°; b. p.
283° at 755 mm.; an in 12 p. c. chloroform solution —35°29'. By
treating with acetic acid anhydride, two isomeric sesquiterpenes were
obtained, having the following properties:
l-ses quiter pene. B. p. = 102°–103° at 6 mm.; 247°–248°
at 748 mm.; an = — 55°48'; no = 1.49287; sp. gr. = 0.8956.
d-ses quiter pene. B. p. = 265.5°–266° at 750 mm.; an =
+ 58°40'; no = 1.50602; sp. gr. = 0-9236.
No crystalline derivatives could be obtained. Isoamyl alcohol,
b. p. 131° (urethane, m. p. 52°) was also identified. Traces of amyl
acetate are probably present.
258. Oil of Eucalyptus Resinifera. G.-H...-K., p. 532.
For the constants of the oil from Eucalyptus resinifera, Smith,
Schimmel & Co.18 give the following: dis” = 0.9123; as – + 6°1'.
§ Bull. from Pathol. Inst. Sydney Univ. 1904 ; S. & Co. Rep. Oct.–Nov., 1904,
p. 37.
11 Compt. rend., 138, p. 157.
12 S. & Co., Rep., April–May, 1904, p 51.
18 S. & Co., Rep. April–May, 1904, p. 96.
40 THE WOLATILE OILS : 1904.
These differ entirely from the constants of this oil as previously
given.14
26O. Oil of Eucalyptus Microcorys. G.-H...-K., p. 533.
A sample of oil obtained from Eucalyptus microcorys F. v. Müll.,
had a sp. gr. = 0.9038 at 15°; an = + 12°29′. 15
269. Oil of Eucalyptus Punctata. G.-H...-K., p. 534.
According to Schimmel & Co.,10 the oil from Eucalyptus punctata,
D. C., has sp. gr. at 15° = 0.9060; an = + 4° 10'. Small quantities
of cuminic aldehyde could be detected.
OILS OF THE UMBELLIFERAE.
296. Oil of Coriander. G.-H...-K., p. 541.
Properties. Authentic specimens of oil of Qoriander, according
to Pancoast, I had a sp. gr. of 0.869 and 0.872 and ap = + 10° 30'.
A commercial sample, quoted as ‘superior', at three times the
price of ordinary oil, had a sp. gr. of 0.873; ap = + 12° 17'.
299. Oil of Celery Leaves. G.-H...-K., p. 547.
Haensel 9 obtained 0.034 p. c. of a greenish-yellow oil from the
whole, fresh celery herb. The oil had the characteristic odor of the
celery root, but had an entirely different odor from the oil of celery
seeds: dis? = 0.8712; a p = + 59.48°; saponification number 42.
Soluble in 5 parts by weight of 90 p. c. alcohol and in 40 parts of
80 p. c. alcohol.
305. Oil of Caraway. G.-H...-K., p. 550.
According to Sadtler & the carvone content of oil of caraway can
be determined, titrimetrically, by the normal sulphite method (see
Oil of Lemon).
307. Oil of Anise. G.-H...-K., p. 558.
Levant anise seed yields* 2 p. c. of rectified oil having the
following properties: dibº = 0.9789; ap = –0°49'; congealing point
+17°. Soluble in 8.5 parts of 80 p. c. alcohol.
14 G.-H...-K., p. 532.
15 S. & Co., Rep. April–May, 1904, p. 96.
16 S. & Co., Rep. April–May, 1904, p. 96.
1 Merck's Rep., 1904, p. #}.
2 Haensel's Ber., 1904, (4), p. 23.
8 Journ. Soc. Chem. Ind., 23, p. 3O3.
UMBELLIFERAE. 41
Oil from Russian seeds, which yield a much larger percent of oil
had the following properties: dis” = 0.9800; an = –0°57'; con-
gealing point + 16.5°. Soluble in 9.9 parts of 80 p. c. alcohol.
309. Oil of Fennel. G.-H...-K., p. 563.
When oil of fennel is kept in contact with light and air, a gradual
increase in the sp. gr. takes place and the solidification temperature
is greatly reduced, some oils not solidifying at all. This is due,
according to Schimmel & Co.5 to the polymerisation and oxidation
of the amethol to anisic aldehyde and anisic acid.
A normal oil has the following properties: d 15° = 0.965–0.975;
solidifying point + 3° — + 6°, sometimes above +8°, soluble in 6
to 8 vol. of 80 p. c. alcohol. An old oil had dis” = 1.0053; solidi-
fying point —8°; soluble in 3 vol. of 80 p. e. alcohol.
The change was still more marked in the case of anethol.
I. Original anethol: d25°= 0.9846; ad = +0°; no 25° == 1.56079;
solidifying at + 21°3'; soluble in 2 vol. of 90 p. c. alcohol.
II. The same anethol after being kept for two years in the light
and partly filled bottle: dgs” = 1.1245; ap = + 0°; no 25°– 1.54906;
did not solidify at — 20°; soluble in 1.5 to 2 vol. of 70 p. c. alcohol.
This shows the importance of keeping essential oils in a proper
way, out of contact from light and air.
312. Oil of Water Fennel. G.-H...-K., p. 568.
Schimmel & Co.6 have isolated from the oil of water fennel, an
aldehyde, isomeric with citral, to which they give the name “phel-
landral.” It has the following properties: b. p. 89° (5 mm.);
d15° = 0.94.45; ap = — 36° 30'. Its semicarbazone melted at 202°
to 204° and its phenylhydrazone at 122°–123°. Upon oxidation by
exposure to the air an acid with the same number of carbon atoms,
C10H16O2 m. p. 144°–145°, was obtained. By oxidation with
potassium permanganate, an acid having the formula C9H1604,
m. p. 115°–116°, was obtained. The distillation of the calcium salt
of this acid yielded isopropyl — 1 — pentanone — 3, which upon
oxidation yielded a- and 3-isopropyl glutaric acids Phellandral was
therefore considered to be p-isopropyl tetrahydrobenzaldehyde:
4 Haensel’s Ber., 1904 (1), p. 4
5 S. & Co., Rep., Oet.—Nov. 1904, p. 42.
6 S. & Co., Rep., Oct.–Nov., 1904, p. 88.
42 THE WOLATILE OILS : 1904.
C—CHO
/
H2O/ Nº H
|
H2ON /CH2
N /
CH
CH
/N
H30/ NCH3
An alcohol, called “androl”, having the formula C10H200 was
also isolated. It had the following properties: b. p. 1979–198°;
dis” = 0.858; ap = — 7° 10'; no = 1.44991. Its phenylurethane
melted at 42°–43°. Small quantities of an alcohol, yielding a
diphenylurethane, m. p. 87°–90°, having a rose like odor, were
isolated.
316. Oil of Angelica. G.-H...-K., p. 570.
Belgian Angelica, seeds 7 yield 1.29 p. c. of a yellow oil; d.15 =
0.8533; ap = + 13.26°; saponification number 16; acetylization
number 35. One gram of oil is soluble in 30 grams of 80 p. c.
alcohol.
75 p. c. of the oil consists of terpenes, of which d-phelland rene
(nitroso derivative, m. p. 104°) and pinene (nitrosochloride, m. p.
103°) were identified.
327. East Indian Dill Oil. G.-H...-K., p. 579.
Apiol from dill Oil has been shown by Thoms 8 to be 5, 6-dimeth-
oxy — 3, 4 — methyleneoxy allylbenzene.
C–CII2OH = CH2
/ N
choºl NCH
|
(H8OC /C
N / N
C O
N
O
N
CH2
7 IIaensel's Ber., 1904, (4), p. 4.
8 Arch. d. Pharm., 242, p. 344.
|PRIMULACEAE, OLEACEAE. 43
OILS OF THE PRIMULACEAE.
340. Primula Root Oil. G.-H...-K., p. 590.
Upon the distillation of 300 kilos of the roots of Primula veris,
L., Brunner * obtained 170 grams of crude primula camphor. The
rectified product boiled at 255°; sp. gr. 1.2155; m. p. 49°. It has
the formula, CoH1004, and upon saponification yields m-methoxy
salicylic acid, m. p. 140°. The so-called ‘primula camphor’ contains
two methoxy groups and is therefore the methyl ester of m-methoxy-
salicylic acid :
C—COOCH3
nº N Sc—OH
|
HC /CH
* /
C—OCH3
OILS OF THE OLEACEAE.
341. Oil of Jasmine. G.-H...-K., p. 590.
According to Sodent jasmine flowers, collected in July and August,
yield 0.077 p. c. of oil when extracted with petroleum ether. The
oil had the following properties: dis?= 0.9955; ap = –1°; acid
number 2.5; ester number 190, equivalent to 51 p. c. of benzyl-
acetate. Flowers collected in September and October, yielded 0.0718
p. c. of oil, d.15° = 0.967; ap faintly to the left; acid number 3.5;
ester number 161, equivalent to 43.3 p. c. of benzyl acetate. The
oil contained a large quantity of indol.
According to Hesse” oil of jasmin, obtained by cold extraction,
does not contain the methyl ester of anthranilic acid, the latter
compound resulting, however, when the extract is distilled. The
flowers, therefore, do not contain free methyl anthranilate, but con-
tain a complex compound which upon distillation or enfleurage
breaks up forming methyl anthranilate. This complex substance is
only partly extracted with petroleum ether from the flowers, so
that extracted oils contain much loss of the ester.
* Schweiz, Wochensch. f. I’harm., 1904, p. 305,
i Journ. f. prakt. Chem. II., 69, p. 256.
2 Ber. 37, p. 1457. g
44 THE WOLATILE OILS : 1904.
OILS OF THE VERBENACEAE.
343. Oil of Verbena. G.-H...-K., p. p. 593.
It is claimed by Stapf1 that verbena oil is not derived from
Andropogon citratus D. C. but in all probability from A. Schoen–
anthus, Linn.
343 a. Oil from Lippia, urticoides.
From the flowers T. Peckolt 2 obtained 0.063 p. c. of a yellowish
oil with blue fluorescence and an odor resembling that of neroli;
sp. gr. 0.908 at 23° C.
343 b. Oil from Lippia geminata.
From the fresh leaves G. Peckolt 8 obtained 0.123 p. c. of volatile
oil. The odor of the leaves reminds of that of sage and thyme.
34.3 c. Oil from Lippia microcephala.
The leaves, the odor of which resembles that of rosemary and
thyme, yielded 0.006 p. c. of volatile oil. Peckolt. 4
OILS OF THE LABIATAE.
346. Oil of Rosemary. G. H.-K., p. 594.
Schimmel & Co.1 have examined authentic English oil of rose-
mary which differs from the French and Dalmatian by its leavo
rotation. It had a strong, but pleasant odor, d.15° = 0.9042; an =
—2°49'; an of the first 10 p. c. == — 6°10'; ester number 9.7; soluble
in 5 vol. of 80 p. c. alcohol with slight turbidity.
In Spain, there is produced besides the ordinary rosemary oil,
an oil called rosemary oil “courant” which is distilled from rosemary
and sage. An oil of this kind had the following constants: digº =
0.9258; ap = + 14° 35'; an of the first 10 p. c. = + 0°40'; acid
number 0.9; ester number 35.7; soluble in 1 vol. of 80 p. c. alcohol.
According to Schimmel & Co.,” a rosemary oil is sold on the
market, which is nothing but a fraction of oil of camphor.
Plla run. Journ., 73. p. 85 ; from Bulletin Bot. Dept. Trinidad, 42, p. 71.
Rer. d. (). Pharm. Ges., 14, p. 4.68.
Ibidem, p. 470; see also Revista pharmaceutica, Rio de Janeiro, 1884, p. 184.
lbidem. p. 471.
S. & Co., Rep., Oct.-Nov., 1904, p. 82.
S. & Co., Rep., April–May, 1904, p. 80.
:
LABIATAE. 45
354. Oil of Sage. G.-H...-K., p. 612.
The oil from the broad-leaved variety (yield 0.879 p. c.) possessed
the following constants: D15°=0.9084; ap = –10.06%; saponification
number 13.5; Saponification number after acetylization = 43.5; not
soluble to a clear solution in 15 p. of 80 p. c. alcohol.
The oil from the common, narrow-leaved variety (yield 1.92 p. c.)
had the following constants: D15° = 0.9250; ap = + 13.36°,
saponification number = 10.75; saponification number after acetyl-
ation = 48; soluble in 0.95 p. of 80 p. c. alcohol.
358. Oil of Monarda Didyma. G.-H...-K., p. 616.
Schimmel & Co.8 obtained 0.04 p. c. of oil from the half dried
herb of Monarda didyma, L. It had a golden yellow color and a
pleasant aromatic odor, somewhat like ambergris. d.15° = –0.8786;
ap = —24°36'; soluble in 1.5 to 2 volumes of 70 p. c. alcohol, the
solution becoming turbid upon further dilution.
358 a. Oil of Monarda citriodora. G.-H...-K., p. 153.
From the dried flowering herb of Monarda citriodora, Brandel 4
obtained 1 p. c. of a reddish oil, having a sp. gr. of 0.94.37 at 20°.
It contained 65.6 p. c. of carvacrol (benzoyl derivative of nitroso
compound, m. p. 110°) and also hydrothymoquinone, m. p. 140°.
By the oxidation of fraction 170°–17.5° with potassium permangan-
ate, a crystalline compound, m. p. 124°, resulted.
369. Oil of Wild Thyme. G.-H...-K., p. 628.
Rectified oil of wild thyme 5 is a golden yellow liquid, d15° =
0.9127; an = — 11°; saponification number 38. The oil is com-
pletely soluble in 90 p. c. alcohol, soluble in 1.15 parts of 80 p. c.
alcohol and 74 parts of 70 p. c. alcohol. 8.3 p. c. of the oil distills
over below 170°, 15 p. c. from 170°–200° and 50 p. c. from 200°
to 240°.
372. Oil ol Peppermint. G.-H...-K., p. 630.
FRENCH PEPPERMINT OIL.
Source. According to Charabot and Hebert 6 the systematic
and complete removal of inflorescences from growing peppermint
8 S. & Co., Rep, Oct.–Nov., 1904, p. 97.
4 Pharm. Rev., 22, p. 153.
5 Haensel’s Ber., 1904, (1), p. 10.
6 Compt, rend., 138, p. 380.
46 THE WOLATILE OILS : 1904.
plants, brings about a marked increase in the leaves and therefore
an increase in the percentage yield and absolute weight of oil. Plants
freely exposed to the influence of light contain more oil than if shaded.
ENGLISH PEPPERMINT OIL.
A dulter a tion. From analyses made by Parry and Bennett 7
cedar wood oil is used to adulterate peppermint oil. Three samples
of adulterated oil were found to have the following properties:

-- a - E C
Sp. gr. at 15°............................... 0.9086 ().908() ().9080
(4D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . — 24° — 25° — 24°
no at 20....................................... T.4 (570 1.4670 1.4.673
Total menthol.............................. 48 p. c. 48 p. c. 49.1 p. c.
Panchaud 8 recommends the acetylation method for the assay of
peppermint oil.
JAVANESE PEPPERMINT OIL.
Source. Javanese peppermint oil 9 is obtained from Mentha
ja Vanica, Bl. (Mentha lanceolata, Benth.), which may be a variety
of Mentha at Vensis, L.
Properties. The oil has a pleasant odor which is not a pepper-
mint odor, a bitter taste, and a green color. (115° = 0.9214; an =
+4°40'; soluble in 1.5 volumes of 70 p. c. alcohol. The oil congeals
p:urtly at –60° and liquifies again at — 15°. It contains much pule.
gone and little menthol or menthone.
375 al. Oil from Mentha Citrata.
Mentha citrata, Ehrh., known as “bergamot mint” in Florida,
yields, according to Schimmel & Co.10 0 2 p. c. of oil, when the
young, not flowering, fresh plants are distilled. The oil has a pale
yellow color, and a pleasant lavender-like odor. d.15° = 0.8826;
ap = —5°35'; ester number = 31.28, equivalent to 10.95 p. c. of
linalyl acetate; soluble in 2 vol. of 70 p. c. alcohol. From the frozen
leaves an oil was obtained which had a sp. gr. = 0.8895; on =
7 (Shem. and Drugg., 64, p. 854.
8 Pharm: Journ., 73, p. 85; from Zeitsch. f. Nahrungs- u. Genussmittel,7, p. 707;
from Schweiz. Wochensch r.
9 Pharm. Week bl., 41, p. 108 1.
10 S. & Co., ſtep., April–May, 1904, p. 95.
LABIATAE. 4.7
—1°41’; ester number = 111.28, equivalent to 38.95, of linalyl
acetate.
378. Oil of Patchouly. G.-H...-K., p. 656.
Properties. Schimmel & Co.11 have examined an oil which had
the following properties: dis? = 0.9769; ap = — 55° 45'; acid num-
ber 2.2; Saponification number 4.2; saponification number after
acetylation 15.4. The oil had a dark brown color, was soluble in
1 volume of 90 p. c. alcohol and boiled from 118° (17 mm.) to 151°
(8 mm.).
Composition. About 97 p. c. of the oil consists of one or
more sesquiterpenes and patchouly alcohol. The sesquiterpene cadi-
nene, previously detected by Wallach, could not be identified. Patch-
ouly alcohol, m. p. 56°, 4p in 23.94 p. c. chloroform solution —97°
42', comprises the bulk of the oil. The sesquiterpene patchoulene,
which is readily formed from the alcohol, is probably found also in
the oil.
In the remaining 3 p. c., the following substances were identified :
benzaldehyde (semi carbazone, m. p. 215°); eugenol (benzoyl com-
pound, m. p. 69°–70°); cinnamic aldehyde (semi carbazone, m. p.
208°); a terpene alcohol having a rose-like odor; a ketone (semi
carbazone, m. p. 134°); two bases, one of which yields a salt with
platinum chloride, m. p. 208°.
Soden and Rojahn 12 have isolated from patchouli oil two sesqui-
terpenes. One, having properties similar to cedrene, is a thin color-
less liquid, b. p. at 750 mm. 264°—265°; d.15° = 0.9335; ap20° =
—58°45'. The second boiled at 273°–274° (760 mm.); d.15°=0.930;
ap = + 0.45. Cadinene could not be identified.
Adulteration. Simmons 18 has examined two samples of
patchouli oil which were adulterated with an ester-containing oil.
Although the constants did not vary much from those of a normal
oil, the Saponification number was very high. Considerable quanti-
ties of benzoic acid were obtained from the saponified oil.
380. Oil of Sweet Basil. G.-H...-K., p. 659.
Co m position. Romburgh 14 has detected in the oil from
Ocimum basilicum, L., considerable quantities of eugenol and a new
11 S. & Co., Rep., April–May, 1904, p. 68.
12 Ber., 37, p. 3353.
18 Chem. and Drugg., 64, p. 815.
14 Koninklyke Akad. van Wetensch., Amsterdam, 1904, p. —.
48 THE WOLATILE OILS : 1904.
olefinic terpene, C10H16, called Ocimene. It has properties, similar to
myrcene, but is not identical with it.
From a detailed study on the distribution of the odorous com-
pounds in the basil plant, Charabot and Laloue 15 have drawn the
following conclusions. The oil is formed mainly before the flowering
period. It accumulates particularly in the inflorescence. At the
period of seeding the weight of oil increases in the leaf and stem and
decreases in the inflorescence. It is probable that at this period in
the life of the plant, the migration of organic matter towards the
inflorescence becomes retarded so that odorous compounds are con-
sumed without being renewed. The formation of these compounds,
however, still goes on in the chlorophyll-bearing organs, although
at a reduced rate.
The oil from the ieaves and stems is richer in estragol than the
oil from the flowers, the difference becoming smaller during the seed-
ing period. The percent of linalool decreases in the oil from the
flowers while the percent of cineol in the oils from both leaves and
flowers increases during the seeding period.
380 a. Oil from Ocimum carnosum.
The fresh leaves, having an odor resembling that of spearmint
and lavender, when examined by Peckolt, 16 yielded 0.25 p. c. of a
strongly aromatic oil.
380 b. Oil from Ocimum micranthum.
The fresh leaves, examined by Peckolt, 17 yielded 0.14 p. c. of a
fragrant oil, sp. gr. 0.982 at 23° C.
385 a. Oil from Hyptis spicata.
Schimmel & Co.18 obtained 0.005 p. c. oil from the herb of Hyptis
Spicatº (Poit.) Briq. (Mesosphaerum spicatum) which grows abund-
antly in Florida. The Oil had a bright yellow color and a faint
mint-like odor. dis? = 0.915; ap = —27°25'; acid number, 2.17;
ester number, 4.35. Insoluble in 10 volumes of 80 p. c. alcohol. It
probably contains menth one and pulegone.
15 Bull. Soc. Chim., (3) 31, p. 1233.
16 Ber. d. d. Pharm. Ges., 14, p. 373.
17 Ibidem, p. 374.
18 S. & Co., Rep., April–May, 1904, p. 96.
CAPRIFOLIACEE, COMPOSITE. 49
Peckolt 19 obtained 0.07 p. c. of an oil the odor of which
reminded of origanum.
385b. Oil from Hyptis salzmanni.
From the fresh leaves Peckolt 20 obtained 0.145 p. c. of a light
greenish oil, the odor of which resembled that of chamomile and
balm; sp. gr. 0.9018 at 23° C.
385 c. Oil from Hyptis fasciculata.
From the fresh leaves Peckolt 21 obtained 0.15 p. c. of an oil the
odor of which reminded of balm and origanum; sp. gr. 0.903 at 23°.
386 d. Oil from Peltodon radicans.
From the fresh leaves Peckolt 22 obtained 0.08 p. c. of a fragrant
oil, sp. gr. 0.08 at 23°.
OILS OF THE CAPRIFOLIACEAE.
388. Oil of Elder Blossoms. G.-H...-K., p. 663.
The flowers of Sambucus nigra yield 6.087 p. c. of a very dark
oil.28 dao° = 0.8691. When cooled to +18.5° C. or dissolved in ab-
solute alcohol, large quantities of a stearoptene separate out.
OILS OF THE COMPOSITAE.
393. Oil of Dog Fennel. G.-H...-K., p. 667.
The plant from which dog fennel oil is obtained is Eupatorium
capillifolium (Lamarck), Small,” and not Eupatorium foeniculaceum,
Willd., as hitherto given.”
The flowering herb yields about 0.1 p. c. of oil, d.15° = 0.926;
ap = + 18°38'; ester number = 7.11. Forms a cloudy solution with
3.5 volumes of 90 p. c. alcohol. It contains much phelland rene.
4O2. Oil of Ambrosia. Artemisiaefolia. G.-H...-K., p. 672.
The young plants of Ambrosia artemisiaefolia, L., yield 0.15 p. c.
of a green oil with a pleasant aromatic odor.” Sp. gr. at 15° =
0.876; ap = –1°; ester number = 7.94. The oil forms a clear solu-
tion with an equal volume of 90 p. c. alcohol, which becomes turbid
upon further dilution.
19 Ber. d. d. Pharm. Ges., 14, p. 376.
20 Ibid 'm, p. 377.
21 Ibidem, p. 379.
22 Ibidem, p. 375.
28 Haensel’s Ber., 1904, (3), p. 13.
1 S. & Co., Rep., April–May, 1904, p. 96.
gº. . 667
2 § 667.
$ & Co., Rep., April–May, 1904, p. 96.
50 THE WOLATILE OILS : 1904.
412. Oil of Tansy. G.-H...-K., p. 679.
The dried cultivated herb of Tanacetum vulgate yields 0.53 p. c.
of light yellowish-green oil having a very pleasant odor, d.15° =
0.9258; ap = +4.64°; ester number 38. The oil is soluble in 2.5
parts of 70 p. c. alcohol.4 Wallach 5 has shown that oil of tansy
contains principally 8-thujone.
413 a. Oil of Tanacetum Boreale.
The half-dried herb of Tanacetum boreale, Fisch, growing in
Siberia, yields 0.12 p. c of oil having a yellowish color and a power-
ful thujone odor. dis” = 0.9218; ap = + 48° 25'. It forms a cloudy
solution with 8 volumes of 70 p. c. alcohol with separation of much
paraffin.6
415. Oil of Artemisia Vulgaris. G.-H...-K., p. 682.
The Japanese Yomugi Oil is probably obtained from Artemisia
vulgaris, L.7 d15° = 0.9126; ap = — 18° 50'; acid number 1.32;
ester number 16.19.
415 a. Oil of Artemisia herba alba.
Grimal 8 obtained from the entire, non-flowering herb of Artemisia
herba alba, Asso., a plant much used as a remedy in Algeria, 0.3
p. c. of a yellowish-green oil, having a camphor-like odor and a
bitter taste. d.15° = 0.9456; no.20° = 1.47274; ap20° = — 15° 38';
acid number 6.46; ester number 89.23. Soluble in 2.5 parts of 70
p. c. alcohol. The oil does not solidify at –12°.
The oil contains 12.65 p. c. of an alcohol C10H18O and 31.15 p. c.
of an ester, CH3COOC10H17. 1-camphene, cineol, camphor, caprinic
and caprylic acids, were detected.
418. Oil of Wormwood. G.-H...-K., p. 684.
According to Wallach 9 oil of wormwood contains both a- and
8-thujone, principally the latter.
In the hydrocarbon part of wormwood oil Haensel 10 has identi-
fied d-pinene (nitrol-benzylamine, m. p. 122°) and cadinene.
Haensel’s Ber... 1904, (4), p. 23.
Ann., 336, p. 247.
S. & Co., IRep., Oct.–Nov., 1904, p. 97.
S. & Co., Rep., April–May, 1904, p. 94.
Bull. Soc. Chim., (3), 31, p. 694.
Ann., 336, p. 247.
Haensel's Ber., 1904, (1), p. 26.
i
I
UNKNOWN BOTANICAL ORIGIN. 51
428 a. Bardana Oil.
The roots of Arctium lappa, var. minor, and Arctium lappa, var.
tomentosa, yield 0.176 p. c. of oil when distilled with steam.11 The
oil had a yellowish-brown color and was acid in reaction. d25° =
0.9695; ap30° = + 1.24°; acid number 135.5; saponification number
236.6. Readily soluble in 80 p. c. alcohol.
The oil contains palmitic acid, m. p. 62°.
OILS OF UNIKNOWN BOTANICAL, ORIGIN.
111 a. Oil of Calumba. Root.
Haensel 1 obtained 0.00568 percent of oil from the root of
Jateorhiza palmata (Lamark) Miers. The oil has a dark-brown
color, and is acid in reaction dis? = 0.9307; a 5 p. c. solution in
alcohol is optically inactive; acid number 24; saponification num-
ber 54. It is soluble in 96 p. c. alcohol and partly so in 80 p. c.
alcohol, with separation of brown flocculent substance.
4O2. Scheibl Oil.
From an unknown plant of Algeria, Jeancard and Satie 2 obtained
an oil, called Essence de Scheib. The oil had a brown color and an
absinthe-like odor. do.5°= 0.9540; acid number 8.4; ester number
66.5; ester number after acetylation 129.5. It contains 15 p. c. of
phenols, principally the dimethyl ether of pyrogallol.
431. Gouft Oil.
Jeancard and Satie 3 obtained an oil from a plant growing in
Algeria, of unknown botanical origin. The oil, called Essence de
Gouft, had a bright yellow color and a terebinthinate odor. do.5°=
0.9720; ap = — 15° 20'; acid number 1.12; ester number 14; ester
number after acetylation 42. The oil contained pinene (nitroso-
chloride, m. p. 103°) and an alcohol with a geraniol-like odor.
4.33. Essence de Bruyere.
Schimmel & Co.4 have examined an oil originating from Australia,
called Essence de Bruyère, of unknown botanical origin. The oil had
a pale greenish-blue color and a pleasant aromatic odor. d.15° =
0.8587; ap = + 2°44'; soluble in 4.5 volumes of 90 p. c. alcohol.
11 Haensel's Ber., 1904, 2. p. 11.
1 Haensel’s Rep., 1904, (2), p. 9.
2 Bull. Soc. Chim., III, 31, p. 478.
8 Bull. Soc. Chim., III, 31, p. 478.
4. S. & Co., Rep., April–May, 1904, p. 97.
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Q

A flºw ºf the liſtin m in Bimalim
ºf Alkalºids fºr the Year 1905,
By W. A. PUCKNER.
MILWAUKEE,
Pharmaceutical Review Publishing Co.,
1906.
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Pharmaceutical Science Series.
EDITED BY
EDWARD KREMERS.
M O N O G R A D H S.
No. 13.
MIL WAUKEE,
Pharmaceutical Review Publishing Co.
1906.
A Review of the Literature on the Estimation
of Alkaloids for the Year 1905.
By W. A. PUCKNER,
MULWAUKEE,
Pharmaceutical Review Publishing Co.,
1906.
4-12-1/2;
While the year 1905 has not shown any very decided progress in
the estimation of vegetable bases, it has brought forth one contribu-
tion of much importance and considerable merit, namely the Eighth
Decennial Revision of the United States Pharmacopoeia. The
methods of alkaloid determination thereby made official are a credit to
American pharmacy even though they do not represent our knowledge
of today: the subcommittee to whom this part of the revision of the
pharmacopoeia was delegated virtually having completed its labors a
year or two prior to the publication of the book.
As was natural, the “Keller method” was adopted for the crude
drugs when applicable, generally with the modification which I pro-
posed and whereby maceration and percolation are combined and the
need of taking an aliquot portion of the volatile chloroform-ether
solution of the alkaloid is avoided.
Believing that the adoption of the macero-percolation process
for the assay of drugs is a sign that American pharmacy is abandon-
ing percolation for maceration, Peter Mac Ewan, before the British
Pharmaceutical Conference ", says: “So I welcome the macero-shak-
ing process adopted in the majority of assay processes.” He is of
course entirely wrong in his conclusions since here percolation is
combined with maceration, while in the original Keller method
maceration alone is used. The modification was probably adopted
because, by obviating the need of accurately measuring volatile
liquids, it was considered to be better adapted to the needs of the
pharmacist and in his hands to yield more concordant results.
. Further, the tendency of replacing the maceration of the Keller
method by percolation is indicated by the adoption of the adaptation
for pilocarpus, of the method proposed by A. B. Lyons in which the
maceration is done away with altogether. While Mac Ewan considers
the adoption of this assay method as the most interesting feature of
I Am, Drug., 47, p. 95.
2
the new Pharmacopoeia, to me the most striking feature is the incon-
sistency shown in the adoption of assay processes, showing a lack of
cooperation or of system in the work of the subcommittee having this
work in charge. Instead of deciding on some general principle for
the methods of assay to be selected and then to adapt some general
method to suit the needs of each drug, as analysts will naturally
altempt to do, in general each drug has been considered by itself.
While it is desirable to adapt the method of assay for a drug to its
preparations, such relation often is not shown in the official methods,
as will be pointed out when the method of valuation for individual
drugs and their preparations are discussed. Again, while in the ori-
ginal publications for the assay methods which were adopted for the
mydriatic drugs, * a one percent sulphuric acid solution is used to ex-
tract the alkaloids from their chloroform or ether solution, the phar-
macopoeial method directs to extemporize this by diluting normal
volumetric sulphuric acid solution to the required strength. This
change is commendable since it avoids the introduction of an addi-
tional test solution; but why then is the three percent sulphuric acid
directed in the assay of nux vomica not made extemporaneously in
the same way? The following shows a similar lack of coordination
in the work of the several subcommittees having the revision in hand.
It is well known that the term “alkaloid” is subject to several
definitions. While some apply the term to all vegetable bases, that
is, to basic bodies occurring in plants, others restrict the word to
those basic substances derived from, or related to, pyridine. Accord-
ing to the latter interpretation caffeine, theobromine and even
morphine are not alkaloids. Further, whether the first or second
definition be accepted, the term base is still open to different inter-
pretation. While some alkaloids react with water to form hydroxides
which are strongly ionized and hence are “strong bases” and form
well defined salts, the hydroxides of others show little tendency to
ionize, whence their salts, in presence of water, because of hydrolysis
break up into free base and acid. Thus while salts of caffeine may
be prepared, these when dissolved in water are so largely hydrolized
that the free base may be abstracted from such a solution by means
of immiscible solvents. Therefore, even iſ the first definition be
adopted it is still a question whether caffeine is to be considered an
2 Proc. A. Ph. A., p7, p. 297 ; Pharm. Rev., 16, p. 180; Pharm. Rev., 20, p. 457.
3
alkaloid. In the seventh revision of the United States Pharmacopoeia
caffeine is described not as an alkaloid, but as a feebly basic Sub-
stance; yet under the prescribed tests of purity appears one which
“shows the absence of other alkaloids” and one is left in doubt
whether caffeine is considered to be an alkaloid. In the eighth re-
vision it is again stated to be a feebly basic substance, but the test
just referred to is said to indicate “absence of alkaloids” and from
this it would appear that, officially, caffeine is not an alkaloid. With
this point of view the subcommittee on proximate assays appears not
to have agreed, since fluid extract of guarana is required to contain
in 100 cc. “3.5 gm. of the alkaloids from Guarana.”
Two contributions dealing in a general way with alkaloidal
estimations were presented to the British Pharmaceutical Conference:
“Standardization in the new U. S. P.” by Thomas Maben ", and the
presidential address by W. A. H. Naylor * on standardization of
drugs. Naylor reviews the history of alkaloidal standards as shown
by their introduction into the British Pharmacopoeia, discusses the
methods now official therein and the modifications proposed for them.
In this review the suggestions of Naylor will be treated under the
individual drugs. In concluding his address he offered his personal
opinion on certain aspects of the question of standardization: thus he
believes that its aim should be to produce preparations that will re-
present the total therapeutical activity of the drug, except in cases
where the effects of certain definite principles are desired as in pre-
parations of opium in which the presence of narcotine may be con-
sidered objectionable; that the pharmacist should devise processes not
only for the estimation of the chief medicinal constituent, but, as far
as possible, for the several medicinal constituents present in the drug,
which will include principles now disregarded, but which in the
future will be found to modify the therapeutic activity of the drug;
and, while it is an acknowledged fact that there is a growing demand
for definite vegetable principles, yet there is no perceptible decline
in the use of preparations of drugs, and in his belief the extractive
forms of galenicals will be used increasingly if the pharmacist will
equip himself for the successful investigation of problems connected
with the chemistry of drugs.
* *
3. A m. J. Phar., 77, p. 435 ; 13t Col. Drug., 48, p. S2.
4. A m. Drug., 47, p. 75 : Br. Col. Drug., 4S, p 74.
4.
Physiological standardization of drugs. W. E. Nixon ",
replying to the usual objections raised against the physiological or
bio-chemical standardization of drugs, states that the errors due to
the extreme sensitiveness of animals to conditons, can be guarded
against and comparative results readily obtained, that the claim that
animals differed from man was untrue and that every vertibrate
heart responds to drugs in the same way.
Aconite. The method of A. B. Stevens" for aconite has
been made official in the new Pharmacopoeia for the drug, and with a
slight modification is also applied to the fluid extract and tincture.
The valuation of aconite by this method consumes much time because
of the low temperature prescribed for the evaporation of the per-
colate and the difficulty of obtaining a clear filtrate when the evapora-
tion residue is dissolved in dilute sulphuric acid and filtered. But
the procedure is so simple and the decomposition of the alkaloid is so
effectually avoided that the time consumed for the assay may well
be ignored. While the results by other methods often show wide
variation when the weight of the alkaloidal residue is compared with
the result of its titration, the gravimetric and volumetric results ob-
tained with Stevens’ method always show close agreement.
However, J. M. Francis' still believes that the official assay
process fails to determine pure aconitine, and that consequently the
method of standardization is not as reliable as that proposed many
years ago by E. R. Squibb.
G. Fromme * uses the following method: 7 gm. aconite of
medium fineness, 70 gm. ether and 5 gm. 15 percent sodium hydrox-
ide solution are shaken often and vigorously during one-half hour
and then as much as possible poured through a pledget of cotton into
a flask, 1 cc. water added to the ethereal liquid, the mixture well
shaken, put aside until perfectly clear and then 50 gm. or as much as
possible (10 gm. = 1 gm. drug) poured off. This is extracted with
15, 10 & 10 gm. of 1 percent hydrochloric acid. Then the acid extrac-
tions are just neutralized with ammonium hydroxide and the alkaloid
abstracted with 15, 10 & 10 gm. of chloroform and successively passed
through a 3 to 4 cm. plain filter into a 100 cc. tared Erlenmeyer flask.
The chloroform is distilled from a Water bath, the residue twico dis-
*
.
I31. Col. Drug., 4S. D. S.1 : A m. ..]. I "harm., 77, p. 433.
Pharm. Arch., 6, p. 49 ; Proc. A. I’h. A., 51, p. 776.
I3 ul. Pharm. T905, pp. 19, 496.
Geschäftsbericht, Caesar and Loretz, 1905, p. 51.
{
y
7
S
*
:
)
solved in ether, 5 gm. each time, brought to dryness, the residue dried
to constant weight in a desiccator and its weight determined. As a
check the residue is dissolved in a few ce. absolute alcohol, about 20
cc. water and a few drops hematoxylin solution added and its alka-
limity determined with tenth normal hydrochloric acid solution.
Belladonna. See mydriatic drugs.
Cinchona. The method of assay now official, based on the
Keller method, directs the maceration of 15 gm. drug, in No. 80 or
finer powder, with 125 Ce. ether, 25 CC. chloroform and 10 Co. am-
monia water during five hours. From 100 Co. of the decanted liquid
the alkaloids are abstracted with dilute acid. In one-half of the acid
extraction the total alkaloids are determined; in the other half the
other soluble alkaloids are determined by a method which aims at
comparative results only. In my hands the method has failed to
correctly indicate the percent of total alkaloid; when the drug was of
the extreme fineness required and the suggested mechanical shaker
was used, the results still indicated a total alkaloid content far below
that given by other methods. The method has also been criticized
as regards the estimation of ether soluble alkaloid by J. M. Francis. *
He recommends the exclusion of cinchona rubra by physical or bo-
tanical examination; then he believes the adoption of five percent
total alkaloid as a standard will be satisfactory, since, if the red bark
be excluded, all other commercial barks which contain five percent
total alkaloids will be found to contain at least 2.5 percent quinine.
Sidney ('. Gadd " proposes a modification of the B. P. assay
process:
“Take of bark 20 gms., slaked lime 6 gms., mix and triturate
with 20 (c. of distilled water ; allow to stand for one hour ; transfer
to a 350 C'c. flask; add 130 Co. benzolated amylic alcohol and attach
to a reflux condenser ; boil over a water bath for half an hour ; decant
on a filter paper having a diameter of 13 cm.; repeat this with two
successive 40 Co. of benzolated amylic alcohol (benzene 30 Co., amyl
alcohol 10 Ce.). Transfer the contents of the flask to the filter paper.
Wash with 40 Co. hot benzolated amylie alcohol. Take 6 Co. dilute
hydrochloric acid and dilute to 42 Ce. with distilled water. Divide
this solution into four equal portions, and shake the benzolated amylic
alcohol Solution with each in turn. Wash the benzolated amylic
9 Bul Pharm. 1905, 19, p. 364.
10 Pharm. J. (4), 21, p. 134.
alcohol solution with 10 (c. distilled water, and add the washings to
the mixed acid solutions. Nearly neutralize the solution with solu-
tion of ammonia and concentrate to about 20 Ce. If the solution
begins to deposit resinous substances, slightly acidulate. Now make
the concentrated solution exactly neutral with solution of ammonia.
Dissolve 1.5 Gm. of sodium potassium tartrate in 3 Co. of water and
add this solution to the above with stirring. Remove from the Water
bath and set aside for one hour. Filter. Wash and dry the preci-
pitate. Weigh. Eight-tenths of the weight will represent the amount
of quinine and cinchonidine in 20 Gm. of the bark. To the filtrate
add solution of ammonia, collect, wash, dry and weigh the precipitate.
The weight will represent the amount of the other alkaloids in 20
(; m. of the bark.”
Vigeron * proposes a method for the estimation of quinine alka-
loids in chinchona bark in which a quinine relatively free from
cinchonine is prepared, first by using ether as solvent in extracting
the alkaloids, then by converting to sulphate, crystallizing, Washing
the crystalline mass with a saturated solution iſ quinine Sulphate.
Finally the quinine is precipitated as quinine chromate.
P. W. Roberts * bases a method of cinchona valuation on the
imsolubility of the precipitate formed when ammonium sulphocyanate
is added to a solution of cinchona alkaloid containing a zinc salt.
A solution containing one part quinine in 50000 will, in presence of
zinc sulphate, show turbidity on the addition of ammonium sulpho-
cyanate. While the composition of these precipitates is complex yet
precipitation with a known excess of the reagent and estimation of
the residual sulphocyanide was found to give correct results.
The composition of cinchonine-ammonium-zinc sulphocyanate was
4C, H.ON, + 3Zn(CNS), + 2NH, CNS + 4HCNS.
For the determination of the purity of quinine sulphate William
Duncan * proposes the use of lime water in place of ammonia water,
because the former is a stronger base and is more readily obtained of
known purity and strength. In addition to the determination of
solubility be suggests that at the same time the amount of sulphate
radicle be determined by adding phenolphthalein T. S. to the alkaloid
solution and noting the volume of lime water required to produce a
red color. While 20 Co. of a saturated solution of pure quinine sul-
11 J. Pharm. Chim. (6), 21, p. 180 (Chem. Centrbl. 1905, 2, p. 1 99 )
12 Proc. ch" m. soc. , 21, p. 242 (Chem. Centrbl 1906. 1 , p. 1 99).
13 Pharm. J. (4) 20, p. 437 (Chem. Centrbl., 1905, 1, p. 1342).
7
phate will require 2 Ce, lime water to produce alkalinity, 20 Co. of a
saturated solution of cinchonidine sulphate will require 17.5 CC.
Twenty Co. of a saturated solution of a commercial quinine sulphate
required 2.8 Co. lime water to produce alkalinty and 41 Co. were
added to obtain a clear solution. After adding one percent. cinchó-
nine sulphate to the quinine sulphate, 3.3 Co. and 45 Ce. respectively,
of lime water were required.
Coca. The method adopted in the new Pharmacopoeia for coca
is the same as that for the mydriatic drugs except that in the final ex-
traction ether instead of chloroform is directed thereby rejecting
alkaloids other than cocaine. For fluid extract of coca, the method
directed for the mydriatic fluid extracts is directed except that
throughout ether is used instead of chloroform. The standard
adopted is 0.5 percent of ether soluble alkaloid. sº
J. M. Francis " reports assays of fifteen lots of Huanuco drug
ranging from 0.43 to 0.82 percent, averaging 0.57 percent ether
soluble alkaloids; also six assays of Truxillo leaf show 0.46 to 0.83
percent and average 0.69 percent. Francis also notes the deteriora-
tion of the drug with age and reports that a drug stored under the
most favorable conditions showed a decrease from 0.8 percent to 0.63
percent of alkaloid in six months.
M. Greshoff" gives the method proposed by himself in detail
and states that he has found it superior to other methods. This is
confirmed by Dr. Bloementhal, who compared it with the methods of
Keller, Pauchaud and others. Briefly, the method consists in extract-
ing the drug with hot alcohol, evaporating the tincture, dissolving in
water, filtering, extracting the filtrate with ether to remove chloro-
phyl, wax, etc., and finally extracting the alkaloid with ether. The
ether is distilled off, the residue dried in a current of dry air to
remove volatile alkaloids, and finally at 95° C. for three hours.
A. W. K. de Jong" proposes the use of ice-cold ether in the
valuation of coca by the Keller method and claims that he determines
all the coca alkaloids except benzoyle.cgonine. *
Coffee, guarana, kola, etc. The assay method for guarana,
the only official caffeine-bearing drug, directs the drug to be shaken
with chloroform and ammonia water, an aliquot portion of the
14 Bul. Pharm. 1905, 19, p. 4:49
15 Pharm, Weekblä , 42, p. 286 (Proc. A. Ph. A., 53, p. 652; Chem. Centrbl.,
1905, 1, p. 1342.)
16 Rec. trav. chim., 24, p. 307 (Chem. Centrbl , 1905. 2, p. 1198).
S
chloroform filtered out. The chloroform is distilled off, the residue
dissolved in sulphuric acid and water and, after rendering alkaline
with ammonia water, the caffeine is extracted with chloroform and
the chloroform distilled off. Finally the residue is moistened with
ether (to remove adhering chloroform P) and dried. This ether
treatment according to my experiments is unnecessary. These ex-
periments " also deal with the conditions under which caffeine may
be best abstracted from solutions and obtained in condition for weigh-
ing and also with its separation from acetanilid. *. They show that
the customary method of extracting with chloroform, either evaporat-
ing the solvent spontaneously and drying at a low temperature or
distilling it and drying for a shorter time, at a higher temperature
give like results, and that they are not far from the truth. Certain
(lata were obtained which seemed to confirm the claim that caffeine
does not become anhydrous when dried at the temperature of boiling
water, even if continued for days. - * -
To estimate caffeine in coffee Balland " adds magnesium oxide
and extracts with hot water. The aqueous extractions are evaporated
to dryness and ether used to extract the caffeine from the mass.
The ether is evaporated and, to free the caffeine from fat, the residue
dissolved in water and the filtrate evaporated to dryness.
Colchicum. Being a “weak base” whose salts are strongly
hydrolyzed the alkaloid can not be quantitatively abstracted from its
ether or chloroform solution by means of dilute acid and, being an
ester, is rather easily decomposed (saponified); hence the estimation
of colchicine is not a simple matter, especially when the seed, con-
taining much fat, is to be assayed. The methods so far proposed are
far from satisfactory, usually tedious and not exact. To this the
methods found in the new Pharmacopoeia are no exceptions. Espe-
cially in assaying colchicum seed, inexperienced or careless operators
are liable to obtain excessive results because of incomplete removal of
fat from the water soluble alkaloid. 8 m
Conium. What has just been said in regard to the difficulty of
assaying colchicum applies in many ways to conium; also the state-
ment in regard to the danger of obtaining excessive results and, be-
cause the weight of comine chloride yielded by a standard drug is
- - - 17 Proc. A. Ph. A., 53, p. 333.
5
18 Proc. A. Ph. A., 53, p. 292. -
19 J. Pharm. Chim., 20, p. 543 (Chem. Centrbl., 1905, 1. p. 470).
9
less than 0.033 Gm., the retention of little fat will cause a large error
in the result. On the other hand, since the free alkaloid is volatile at
ordinary temperature, its loss by evaporation is rather liable to occur
in case of faulty procedure and cause low results.
J. v. Braun *" has elaborated a quantitative method for the
separation of coniine from other conium alkaloids, which however is
too difficult to permit its application to the valuation of the drug.
While coniine only must be considered the active constituent of
the drug, the other alkaloids are not present in sufficient amounts to
modify the action of the drug. Therefore, W. A. H. Naylor * con-
cludes that a standard for total alkaloid answers all practical pur-
poses. T. Maben “discusses the standard for conium.
Gelsemium. To determine the amount of alkaloid in gelsemium
L. E. Sayre ** extracts the drug with alcohol, evaporates the percolate
to dryness and extracts the residue with water acidulated with sul-
phuric acid. The acid solution is extracted with chloroform, to re-
move a substance which the author terms gelsemic acid, made alka-
line with sodium hydroxide and the alkaloid abstracted with chloro-
form. The alkaloidal residue remaining after evaporation of the
chloroform is further purified by dissolving in acidulated water,
neutralizing with alkali and again extracting with chloroform.
Guarana. See coffee etc.
Hydrastis. The method of assaying goldenseal now official
depends on the slight solubility of berberine in ether for its separa-
tion from hydrastine. While one would naturally expect to find the
method of assaying the preparations of goldenseal based on the same
principle, yet in the valuation of the fluidextract and tincture the
more complete removal of berberine by precipitation as berberine
iodide as proposed by Gordin and Prescott “ is directed. Since the
alkaloid isolated in the first method is less pure than that obtained in
the second, a drug, according to the official assay process, found to
contain 2.5 percent will yield a fluid extract, which when assayed by
the process for the fluidextract of hydrastis will be found to contain
less than this amount; this perhaps is one of the reasons why the
standard of the fluid extract is but 2 percent, although the drug must
20 Ber, d. chem. Ges., 3 S, 31 OS.
# # 83; # 33 &
23 Proc. A. Ph A., 53. 282.
24 Am. J. Pharm., 7 1, 257.
1()
contain 2.5 percent. This difference has been criticised by T.
Maben, º' who considered that this decrease of 20 percent was made
to allow for loss of alkaloid through incomplete extraction of
the drug.
Hyoscia mus. See mydriatic drugs.
Ipecac. For the valuation of ipecac the typical Keller method is
directed in the new pharmacopoeia: to 15 Gm. drug in No. 80 (!)
powder are added 115 Co. ether, 35 Co. chloroform, 3 Ce, ammonia
water and after a time 10 Co. water and, after maceration, 100 CC. of
the clear solution poured off and taken to represent 10 gm. of drug.
To reject the inert psychotrine ether is used at the end in extracting
the alkaloids. Finally the alkaloidal residue is titrated with hema-
toxylin as indicator and from the volume of tenth normal acid re-
quired for neutralization the “ipecac alkaloids” are calculated.
Because of the tendency of ipecac alkaloids to discolor, their
titration often is unsatisfactory. The following simple method by
G. Fromme * is designed to overcome this titration difficulty: 6 Gm.
of drug, in fine powder, 120 Grm. ether and 5 Gm. ammonia water are
shaken during one-half hour, put aside to settle and then 100 Gm.
decanted through a pledget of cotton. The ether is distilled off, the
residue dissolved in 5 CC. absolute alcohol, 20 Co. ether, 10 Co. water
and 3 drops hematoxylin solution added and then tenthnormal acid
run in ; toward the end of the titration 30 Co. water are added grad-
ually and the addition of Volumetric acid continued until the color
change is complete.
Kola. See coffee etc.
Mydriatic drugs. As a basis for the valuation of the my
driatic drugs, namely belladonna leaves, belladonna root, hyoscia mus.
*copola and stram monium, the new Pharmacopoeia uses the
modification of the Keller method, which I have advocated. 27 The
method avoids the taking of an aliquot portion of the volatile ether-
chloroform solution by using a smaller weight of drug and exhausting
it by a combination maceration-percolation process. For fluid ex-
tracts of belladonna root, hyosciamus, scopola and strammonium, the
method which I proposed “” is directed. For the valuation of tinc-
tures of belladonna leaves, hyosciamus and strammonium the phar-
25 Br. Col. Drug., 48, 8:3.
28 Geschäftsbericht, Caesar & Loretz, 1905, 43.
2. Pharm. R. v., 16, p. 180; Pharm. Rev., 20, p. 457.
28 Pharm Rev., 16, p. 303.
1i
macopoeial directions are to evaporate 100 cc. of the tincture to 10 cc.
and then to follow the method used for the fluid extracts. The assay
method used for fluid extracts of the mydriatic drugs is also adapted
to their solid extracts by dissolving them in a mixture of alcohol,
water and ammonia water. Evidently having in mind the little prac-
tice which the pharmacist has in the estimation of alkaloids, these
methods are given in considerable detail. But in at least two particu-
lars the wording is not happily chosen. Thus when extracting with
immiscible solvent the specification “shake the separator for half a
minute” is liable to convey the impression that vigorous agitation is
required. Such action may be the cause of forming emulsions. Also,
in the case of hyosciamus, in the directions given for the evaporation
of the chloroform prior to the titration, not sufficient stress is laid on
the importance of ensuring the complete evaporation of the volatile
organic bases present in henbane. **
G. Fromme * believes that ether should be substituted for the
other-chloroform mixture usually used whenever the alkaloid to be
determined is readily soluble in the former and offers a modification
of the usual Keller method in which the drug is extracted with pure
ether. **
The alkaloidal content of the mydriatic drugs, especially bella-
donna and its preparations, has received some consideration. E. H.
Farr and R. Wright * report that the alkaloid in fourteen samples
of belladonna root ranged from 0.31 percent to 0.64 percent, with an
average of 0.44 percent, and recommends that as a minimum 0.4 per-
cent be required. He also reports that the alkaloidal strength of
belladonna root extract is higher when strong alcohol is used, thus
90 percent alcohol gave an extract containing 3.7 percent alkaloids,
while with 50 percent alcohol the extract contained 1.9 percent. H.
John Henderson * considers 0.4 percent as a minimum too high for
belladonna root. He reports that seven lots of 800 to 900 pounds
each assayed 0.46, 0.54, 0.33, 0.55, 0.32, 0.42, 0.36 percent; two lots
contañed 0.066 and 0.080 percent, and that for a considerable time
belladonna root containing more than 0.3 percent was not obtainable.
The alkaloidal content of 30 lots, not English, ranged from 0.116 to
29 Pharm. Rev., 23, p. 178.
so Pharm. Rev., 23, p. 1 75.
S1 (Seschäftsbericht, Caesar & I, oretz, 1905, p. 87.
82 Pharm. J.. (20), p. 546 (Chem, Centrbl., 1905, 1, p. 147S).
S3 IPharm. J. (4), 21, p. 191 (Chem. Centrbl., 1905, 2, p. 912)
12
0.547 and averaged 0.270 percent. J. M. Francis “ reports that
twenty lots of belladonna leaves, purchased during 1904 and 1905,
contained from 0.23 to 0.40 percent with an average of 0.31 percent.
The official standard for hyosciamus and fluid extract of hyosciamus,
Francis " considers too low and claims that a drug of fair quality
will easily average 0.10 percent of mydriatic alkaloids. On the other
hand Thomas Maben "" considers the U. S. P. standards for henbane
and its preparations satisfactory. -
|
Continuing his experiments on the separation of alkaloids, espe-
cially those of the mydriatic drugs " from the volatile bases often or
usually present in the leaves of these drugs, H. Thomas * gives the
details of a method which will accomplish the isolation of atropine
when the presence of volatile organic bases, ammonium salts or free
ammonia is suspected. The sulphuric acid solution of the alkaloid is
treated with 10 cc. potassium-bismuth iodide solution, prepared by
pouring a solution of 80 gm. bismuth submitrate in 200 gm. nitric
acid, sp. gr. 1.18, into a concentrated solution of 272 gm. potassium
iodide in water and, after removal of potassium nitrate crystals
formed, diluting to 1000 cc. The precipitate is collected on a filter
of 9 cm. diameter, and washed with 10 cc. 5 percent sulphuric acid.
The precipitate and filter are transferred to a separator, a trituration
of 10 gm. crystallized sodium carbonate and 10 cc. 10 percent sodium
hydroxide solution added and the mixture shaken vigorously during
ten to fifteen minutes. The alkaloids are then extracted with ether,
agitation for twenty minutes each time, being directed.
Nux Vomica. The valuation of nux vomica in the new phar-
macopoeia directs an aliquot portion method; finally, the brucine is
destroyed with nitric acid according to the conditions worked out by
H. M. Gordin, " and the strychnine isolated and titrated. To the
wording of the directions given a criticism may be made which in a
general Way applies to many assay methods and which has already
been spoken off, when discussing the mydriatic drug assays. Namely,
While manifestly it was attempted to prepare directions which one
but little versed in analytical practice might follow, the results ac-
34 Rul. Pharm. 1905, pp. 19, 362.
35 Ibidem.
36 Br. Col. Drug., 48, p. 83.
3. É.º. º.º. 23, p. 178. - *
€ l’. Cl. arm. Ges., 15, p. 85 (Chem. Centr () f\ *
39 Proc. A. Ph. A., 50, #6. ( entrbl, 1905, p. 1, 1341).
13
complished in this direction are far from satisfactory. Thus, in the
assay of nux vomica it no doubt was intended that the volumes of
ether, chloroform, alcohol and ammonia water specified were to be
added to the drug and that this was to be considered equal to 200 CC.
A strict interpretation of the direction necessitates that somewhat
more than 200 Ce. of a mixture of ether, chloroform, alcohol and
ammonia water, in the proportions indicated, be prepared and that
then 200 Ce. of this mixture be measured. Further on, the directions
to “evaporate all the chloroform by means of a water bath very care-
fully, to avoid decrepitation” are superfluous to those experienced in
strychnine estimations, but entirely insufficient to those for whom
these directions apparently were intended. Either the addition of
amyl alcohol as recommended by Gordin should have been retained,
or else evaporation from a dish at room temperature directed. Fin-
ally, the directions to dissolve the alkaloid in 6 Ce. normal acid, 80
Co. water and 20 20 cc. ether will cause much annoyance because of
the slowness with which solution will be effected.
The directions for the valuation of the mux vomica preparations
might be criticised in about the same manner. Personally, I have
given them but a limited trial, but in these trials I found it im-
possible to complete the assay when the official directions were ad-
hered to.
D. Lloyd Howard * records experiments of separating strychnine
from brucine by means of nitric acid as recommended by Keller.
T]epending on conditions the results may easily be either too high or
too low, but correct results may be obtained only if the temperature
is kept sufficiently low during the nitric acid treatment.
W. H. Lenton " finding that Bird's method formed persistent
emulsions when applied to the powdered extract, offers the following
modification. To 10 Co. ether, sp. gr. 0.52, and 10 Co. chloroform
contained in a separator add 2 Gm., then 5 Co. water, shake vigorous-
ly and draw the chloroform-ether layer into another separator Agitate
it with 5 CC. Solution animonium carbonate, 1 in 10, and draw it off
into a third separator and here again shake it with 5 Co. ammonium
carbonate solution. Extract twice after this, using 10 Co. ether and
10 CC. chloroform each time and carry each extraction through the
Separators containing the ammonium carbonate solution. From the
40 Anaiyst. 30, 261 (Chem. Centrbl., 1905, 3, 931.)
41 Pharm. J. (4), 21, S64 (Br. Col. Drug., 4S, 540),
14
united ether-chloroform extract the alkaloid in the usual manner.
Lenton prefers the ſerrocyanide method of separating strychnine
from brucine to the nitric acid method and states that the results
obtained by the nitric acid separation are somewhat erratic and cer-
tainly not comparable with the ferrocyanide method.
Opium. To the disappointment of the many who have been
favorably impressed with the concordant results yielded by the
Stevens method, the revision committee pursued a conservative course
and retained the assay method of the old pharmacopoeia for opium,
modified only by subtracting from the weight of crude morphine ob-
tained the impurities insoluble in lime water.
An increase of ammonia water from 3.5 Co. to 4 CC. in the official
method of opium assay having been proposed, C. E. Wanderkleed “
determined the effect of such modification. He finds that while it is
true that a somewhat greater weight of crude morphine is thus ob-
tained, the increase in weight is due not to morphine, but to im-
purities such as calcium meconate. This he determined by titrating
the crude morphine. E. Mallinckrodt, jr., and E. A. Dunlap * have
determined the composition of the meconates contaminating the
morphine obtained by the process of the U. S. P. 1890 and have
isolated the calcium-ammonium meconate, CaMH, C, H.O., containing
either two or three molecules of water. Since this salt will require
more acid for neutralization than will an equivalent amount of
morphine, the determination of the purity of the morphine obtained
in an opium assay by means of a titration with acid is incorrect.
A. and Albert Petit, * appointed to report on the current
methods of determining morphine in opium, recommend. the lime
method for the next edition of the French Codex. The morphine
obtained is to be dried at 100° C. and then washed with chloroform.
It is to be perfectly soluble in a solution of alkaline hydroxide.
T. C. J. Bird * has worked out a method of approximately deter-
mining the amount of morphine in camphorated tincture of opium.
Phys stigma. Assay methods for physostigma and extract of
physostigma are now official. For the drug the standard is “not less
42 Apoth. 2, 534.
43 .J. A. m. chem. Soc., 27, 946.
44. J. Pharm. chim., (6), 21, 1 ()7, (Proc. A. Ph. A., 58, 656.
45 Pharm. .J. (4), 21, 154.
15
than 0.15 percent of alkaloids soluble in ether, for the extract 2 per-
cent is required.
W. A. H. Naylor * comments on the need of a standard, com-
mercial extracts having been found to vary from 1 to 10 percent of
total alkaloids. According to recent investigation calabar bean con-
tains three alkaloids, eserine, eseridine and eSeramine, but since their
action and also the relative proportion in which they exist in the
drug is not known with any degree of precision, a determination of
total alkaloids must suffice for the present.
H. Beckurts * states that calabar beans contain besides physo-
stigmine, also eserine and calaberine, the latter having tetanic action.
That the first two, but not calabarine, is soluble in ether, while all
three are soluble in chloroform. On the addition of sodium hydroxide
or sodium carbonate, the bases decompose and the solution assumes a
red color; if ether and then sodium or potassium bicarbonate is added
to the alkaloidal solution decomposition does not occur. Methods of
valuation for the drug and extract have been worked out which are
based on these considerations.
Pilocarpus. For pilocarpus the eminently practical method
of A. B. Lyons * is directed in the new pharmacopoeia. While in my
modification of the Keller method maceration is followed by percola-
tion, Lyons discards maceration altogether and extracts the alkaloid
by percolating the drug with chloroform in presence of ammonium
hydroxide. The method also avoids the use of aliquot portions.
For fluid extract of pilocarpus and some other fluid extracts the
pharmacopoeia directs the old “sand method” in which the fluid
extract is evaporated to dryness in a dish containing sand and this
dry mixture then assayed; a useless procedure in view of the good
results obtained with methods patterned after those used for the fluid
extracts of the mydriatic drugs.
The standard adopted requires the drug to contain “not less than
0.5 percent alkaloids” and the fluid extract is adjusted so that 100 cc.
shall “contain 0.4 gm. of the alkaloids of pilocarpus.” W. A. H.
Naylor * believes that the value of jaborandi should not be based on
the determination of its total alkaloids, but on its pilocarpine content
46 Br. Col. Drug., 48, 77.
47 Apoth. Ztg., 20, 670.
48 Proc. A., Ph. A., 5 1, 254.
49 Br. Col. Drug., 48, 78.
16
instead. He concludes that the inference to be drawn from Jowett’s
chemical investigation and Marshall’s physiological experiments is
that the preparations of jaborandi should be assayed for pilocarpine
and not for total alkaloid, and, further, that inasmuch as pilocarpine
possesses acid properties the fixed alkalies should not be used in asso-
ciation with “shake-out” solvents. Jowett has given a method by
which pilocarpine can be separated from a mixture of isopilocarpine
and pilocarpidine, but no process known to Naylor has been published
which is capable of determining within 5 per cent the amount of
pilocarpine present in a preparation of jaborandi.
E. W. Mann "" comments on the low alkaloidal content of jabo-
randi and reports on five samples submitted in response to a request
that good drug, Pilocarpus jaborandi, if possible, be supplied. No. 1
consisted of P. racemosus and contained 0.26 percent alkaloid. Nos.
2, 3 and 4 consisted of P. pennatifolius and contained respectively
0.13, 0.21, 0.16 percent alkaloid. No. 5 was a mixture apparently of
P. pennatifolius, P. jaborandi and a hairy leaf, either belonging to
P. trachylopus or being a hairy variety of P. jaborandi and contained
0.43 percent total alkaloids. In the determination of the alkaloidal
content the method of the U. S. P. VIII was employed. The total
alkaloids in No. 5 were tested for pilocarpine content * and indicated
that the specimen contained 0.30 percent of pilocarpine. Mann pro-
poses that galenical preparations of jaborandi should be assayed to
contain a definite amount of pilocarpine instead of total alkaloids.
Pomegranate. Further experiments on the valuation of pome-
granate have been made by G. Fromme. * While he provisionally
had concluded “” that the drug contained some salt of ammonium or
similar body and that the variable results in the valuation were due
to this body, from his further study he now concludes that such is not
the case. The variable results obtained are due to loss of pomegranate
alkaloids through volatilization.
The demonstration of the absence of ammonia was based on the
consideration that from an aqueous liquid containing free ammonia
ether extracts considerable of it, while only traces are removed by
extraction with chloroform. He also demonstrated that chloroform
50 Br. Col. Drug., 40, 493.
31 Yearbook Pharm, 1899), 4:37.
52 Geschäftsbericht, Caesar & Loretz, 1905, 1:3.
53 Pharm. Itev., 2:3, 206.
17
must be used to abstract the alkaloid from an alkaline aqueous solu-
tion, that the alkaloids may satisfactorily be converted to chlorides
and weighed and that these chlorides are soluble in chloroform and in
absolute alcohol. For the determination he gives iodeosin the prefer-
ence over hematoxylin. Several methods of valuation are proposed:
a) 7 Gm. drug, 70 Gm. ether, 5 Gm. 15 percent sodium hydroxide
Solution are shaken during one-half hour, then as much as possible
of the ether poured through a pledget of cotton into a flask, here
shaken with five to ten drops of water and put aside until perfectly
clear. 50 Gm. of this, representing 5 Gm. drug, are transferred to a
flask, previously rinsed with hydrochloric acid and repeatedly with
distilled water, then 30 Ce, water, a few drops of iodeosin solution
added and tenthnormal hydrochloric acid run in gradually with con-
stant shaking until the solution is colorless. b) Proceding as before,
the 50 Gm. of the clear ether solution, representing 5 Gm. drug, are
extracted with 20, 10, 10 Ce. 1 percent hydrochloric acid, the acid
extractions rendered just alkaline with sodium hydroxide and ex-
tracted with 20, 10, 10 Co. chloroform. The chloroformic extractions
received in a tared flask, mixed with five drops of hydrochloric acid
and the chloroform distilled or evaporated. The residue is dried in
an oven at 70-80 degrees and then over sulphuric acid to constant
weight and 184 parts taken to represent 147.5 parts alkaloid. c) To
the clear ether solution obtainoed as before a few drops of hydro-
chloric acid are added and the ether distilled off. The residue is dis-
Solved in a little chloroform and 50 Gm. petroleum benzine added, on
standing the alkaloidal chlorides separate out and adhere firmly to
the container; the liquid is poured off, the flask rinsed with a little
petroleum benzine and the flask and contents dried as in the pre-
ceeding method.
Scopola. See mydriatic drugs.
Stramonium. See mydriatic drugs.
University of Illinois, School of Pharmacy.
MONOGRAPHS.
4. Popular German Names. This popular pamphlet has been revised
twice by its author, Dr. Fr. Hoffmann. 0.
2. Reagents and Reactions known by the names of their authors.
‘. . Based on the original collection of A. Schneider; revised and en-
larged by Dr. Julius Altschul; translated from the German by Dr.
Richard Fischer, Asst. Professor of Practical Pharmacy at the
University of Wisconsin. Although imperfect in many respects, this
compilation has proven a convenient aid in the laboratory and on
the desk. A revision is now in progress. As long as any copies of
the first edition remain, they can be had for O.25
3. Popular Scandinavian Names. A compilation of popular Swedish
r names of drugs and medicines by Harold Bruun, with formulas for
. . . the preparation of a number of preparations riot generally found in
f .J American reference works. This list is also being revised. Copies still
f on hand can be had for $0.15
-4. Early Phases in the Development of Pharmaceutical Legis-
lation in Wisconsin. An account by Edward Kremers of the evolu-
tion of the first local pharmacy law in Wisconsin with the documents
on which the account is based. Pamphlet, pp. 43. $0.50
5. Some Cuban Medical Plants. While collecting plants in Cuba.
*, during the year 1895 and 1896, Prof. R. Combs had his attention
directed to numerous plants of the island used as domestic remedies.
Pamphlet, pp. 20. $0.15
6. History of the Art of Distillation and of Distilling Appara-
tus. By Oswald Schreiner. Pamphlet, pp. 59, with 65 intº
0.3
7. The Crude Drugs and Chemicals of the United States Phar-
macopoeia (1890) and the Preparations Into Which They
Enter. By W. O. Richtmann. Pamphlet, pp. 55. Now being “;
\
s. Progress in Alkaloidal chemistry, 1993. A collection/
stracts by Dr. H. M. Gordin. Pamphlet, pp. 40. /
3. 9. The singuiterpenes. A monograph by Oswald Schreiner.
- pp. tº
10. Progress in Alkaloidal Chemistry for too.…'
Brochure, pp. 94. /
11. The Volatile Oils: 1904. By I. W. Bran
12. The Balance. By I. W. Brandel and
‘. . . pp. 49, with 48 illustrations.
13. A Review of the Literature on tº
for the Year 1905. By W. A. P.”
*. (In course of p
- –Progress in alkaloidal ch
—Volksbenennungen der b
derselben in brasiliani
sprache adoptirten N
and will soon be is
ſºdics tº




BIBLIOGRAPHIES.
J%.28.5%
1. Chemical Biography of Morphine. From 1875 to 1897, with
an index of authors and subject index. By H. E. Brown. Pamphlet,
pp. 60. $0.40, ,
-**
2. Santonin. Bibliography, with abstracts of methods of production
etc. From 1830 to 1897. By A. Van Zw aluwenburg. Pamphlet.
pp. 11. *. $0.10
3. Bibliography of Apiol. From 1855 to 1896. By A. Van Zwa-
luwenburg. Pamphlet, pp. 4. $0.05
4. Bibliography of Spirit of nitrous ether, and ethyl nitrite.
Up to 1899. By W. O. Richtmann and J. A. Anderson.
Brochure, pp. 180. $1.00
5. Bibliography of aromatic waters. From 1809 to 1900 incl.
By W. O. Richtmann. Brochure, pp. 219. $1.00
In addition to the pamphlet form, these bibliographies will be found
very convenient for card catalogues which can be kept up to date as indi-
cated by the following fascimile reproduction of such a card.

#º º, .
º
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*.*, *
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,7°53
Progress in Alkaloidal Chemistry
During the Year 1905. º
By H. M. GORDIN.
MILWAUKEE,
Pharmaceutical Review Publishing Co.
1907.


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EDITED BY
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No. 17.
MILWAUKEE,
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Progress in Alkaloidal Chemistry
During the Year 1905.
By H. M. GORDIN.
MULWAUKEE,
Pharmaceutical Review Publishing Co.
1907.
(4.4%
5–7 *.
2% e-2,----- le-V.
Aſ – 22 - 6
Progress in Alkaloidal Chemistry during the Year 1905.
By H. M. Gordin.
The past year has been enriched by a great many important in-
vestigations in the domain of alkaloidal chemistry. Among the
more important contributions might be mentioned the investigations
of Knorr, Pschorr, Freund and Wongerichten on the constitution of
morphine, codeine and thebaine which are designated by Knorr as
the morphium alkaloids. The supposition of the presence of a so-
called “ether” oxygen atom in these alkaloids seems not to be in
accord with the results of many experiments and new constitutional
formulae for these bases are proposed by Freund.
The constitution of sparteine is being cleared up by the work of
Moureu and Valeur and that of pilocarpine by the investigations of
Jowett and Pinner.
Several new alkaloids were isolated by Dunstan and his collabo-
rators from some East-Indian aeonite plants and another new
alkaloid was discovered by Pavesi in Papa ver dubium. A number
of researches upon Solanine by various authors have been carried
out but the lack of accord in the results seems to indicate great
difficulty in obtaining the base in a state of absolute purity,
In the following review I shall begin with an investigation of the
general behavior of bases towards alkylization, and then take up in
alphabetical order the alkaloids whose chemistry has been investigated
during last year. *
Bases.
A. Pinner and A. Franz have investigated the influence of in-
different solvents at different temperatures upon the alkylization of
organic bases. It had been shown previously that when ethyl
bromide is added to an ethereal solution of piperidine, crystals of
piperidine hydrobromide separate out, but if the whole mass be
heated to 100° in presence of a little alcohol the hydrobromide of
ethyl piperidine is formed. In experimenting with piperidine, dipro-
pylamine, ethylamine, amylamine and benzylamine the authors have
2
arrived at the conclusion that the results of alkylization depend
upon the velocity of the reaction, the strength of alkalinity of the
bases and the solubility of the products formed in the reaction.
When an alkylhalide acts upon a secondary base the product is a
salt of a tertiary base.
R”=NH + R'Br = R” = N.R.'
* /N
H. Br
If the tertiary base underlying this salt does not differ in strength
from the original secondary base some of the tertiary base is set free
by the action of the free secondary base which in the beginning of
the reaction is still present in the liquid. If equimolecular quantities
of secondary base and alkyl halide are used and the Secondary base
has a greater tendency to react with the alkylhalide than the tertiary
base more and more of the salt of the tertiary base will be formed
in the reaction, so that at the end of the reaction there will be
present the salt of the tertiary base with only a little of the salt of
the secondary base. If (as is usually the case with ether or benzol)
the salt of the secondary base is less soluble in the solvent used than
the salt of the tertiary base the salt of the secondary base will
separate out as soon as it is formed, so that in the solution there
will remain the free tertiary base, traces of the salt of the tertiary
base, some unchanged secondary base and some unchanged alkyl
halide. If the alkyl halide reacts easily with the tertiary base, a
quaternary base is formed which also separates out. Hence as
separated out substances we will have the salt of the quaternary
and the salt of the secondary base whereas in the solution will remain
a mixture of the free secondary base and the free tertiary base.
If the alkyl halide does not easily react with the tertiary base
no salt of the quaternary base will be formed, and the reaction can
then be represented by the following equation:
2 R'' – NH + 2 R/Br = R’’= NH + R^ = N.R.' -- R'Br
/N
H. Br
i. e. the salt of the secondary base will separate out and in the
solution will remain the tertiary base and half of the alkyl halide
taken,
As alkyl iodides have a greater tendency to form quaternary
bases than alkyl bromides or alkyl chlorides it is best to use one
3
molecule of the alkyl bromide with two molecules of the Secondary
base in etheral solution at ordinary temperature. As according to
the last equation no quaternary base is formed in this case, the solid
salt of the secondary base can be filtered off and the tertiary base
can be easily obtained from the ethereal solution.
If it is difficult to obtain the secondary base it is best to use
equimolecular quantities of base and alkyl halide and work in ethereal
solution at 100°. In this case the chief product is the salt of the
tertiary base. It is better yet to use alcohol at Ordinary tempera-
ture in this case. Though the reaction is slower the Salt of the
tertiary base is purer and, particularly in the case of allyl com-
pounds, free from oily impurities.
In the alkylization of primary bases it is more difficult to obtain
pure products than in the case of secondary bases for the reason
that in ethereal solution the reaction velocity between the alkyl halide
and the primary base is in most cases less than between the alkyl
halide and the secondary base. The alkyl halide reacts, therefore, at
the same time with the primary base and with the secondary base
formed in the reaction. Besides, the solubilities of the salts of the
primary and the secondary bases generally differ so little from each
other that it is difficult to obtain pure products.
From equimolecular quantities of ethylamine and ethylbromide
in ethereal solution the authors obtained a mixture of salts of
the primary and the secondary bases which separated out leaving in
solution the tertiary base. With allylamine and ethyl bromide no
definite compound could be obtained. With benzylamine and ethyl
bromide the pure salt of the primary base crystallized out leaving
in solution the free secondary base in pure condition. *
Ber. Dtsch. chem. Ges. 38, p. 1539.
Aconite Alkaloids.
W. R. Dunstan and A. E. Andrews have isolated a new alkaloid
from Aconitum chasmanthum which they named indaconitine. The
alkaloid was extracted by percolating the powdered root with a
mixture of methyl and amyl alcohols, the methyl alcohol removed
by distillation under reduced pressure and the extract shaken out
with acidulated water. After making the liquid alkaline with ammonia
the alkaloid was extracted with ether. The alkaloid is soluble in
acetone, alcohol, chloroform or ether but insoluble in petroleum
4.
ether. The alkaloid is best purified through its hydrobromide which
can be recrystallized from water or by adding ether to its alcoholic
solution. After setting the alkaloid free from the hydrobromide it
crystallizes from ether in fine needles. A peculiar property of inda-
conitine is its capability of crystallizing in different forms from the
same solvent according to the purity of the alkaloid and the con-
centration of the solution. The alkaloid melts at 202–203°. Like
aconitine it forms a erystalline permanganate and also resembles
aconitine crystallographically. It has a specific rotation of +18°17'
and its formula is Ca 4H47NO.10. Like aconitine it contains four
methoxyl groups. The hydrobromide when recrystallized from water
and dried at 100° melts at 183—187°; but when recrystallized from
alcohol-ether it melts at 217–218°. *
The hydrobromide and hydrochloride are leavorotatory. The
hydrochloride contains three molecules of water of crystallization
and melts at 166–1 71° when anhydrous.
A nitrate was obtained by dissolving the base in dilute nitric
acid and recrystallizing the salt from ether-alcohol. An aurichloride
was obtained in crystalline form from a mixture of ether and chloro-
form. The crystals contain one molecule of chloroform which is
removed at 100°. Unlike aconitine aurichloride this salt cannot be
obtained in several modifications.
The physiological action of indaconitine is similar to that of
aconitine. As is the case with the other “aconitines,” the toxic
action of indaconitine is virtually abolished by the removal of the
acetyl group which occurs in the formation of indbenzaconine, an
alkaloid which is scarcely poisonous.
By heating an aqueous solution of indaconitine an acetyl group
is eliminated and indbenzaconine is formed
CS4EI47 NO10 + H2O = CH3.002H + Ca2H45NOo
Indaconitine. Indbenzaconine.
The indbenzaconine could not be obtained in crystalline form.
Like benzaconine it is dextrorotatory. It is only very slightly
poisonous. Several salts of indbenzaoonine were obtained in crystal-
line form. The alkaloid forms a chloraurate and an aurichlor-
derivative analogous to the corresponding benzaconine derivatives
5
Alcoholic sodium hydroxide hydrolyzes indaconitine forming inda-
conine, identical with pseudoaconine, benzoic acid and acetic acid.
Caa H47NO.10 + 2 H2O = C25H41NO3 + Co. HäCO2H + CH3CO2H
In daconitine In daconine.
Indaconine crystallizes from alcohol or acetone in crystals con-
taining alcohol or acetone of crystallization. It reduces Fehling's
solution and readily decolorizes potassium permanganate. The
identity of indaconine with pseudoaconine was shown by a compari-
son of their melting points, optical rotation, crystalline form and
physiological action all of which were found to be the same for both
bases. No crystalline salts could be obtained from indaconine.
When indaconitine is heated to its melting point acetic acid is
split off and a new base, pyroindaconitine, is formed. The new base
could not be obtained in crystalline form but the hydrobromide
crystallizes well.
When the hydrochloride of pyroindaconitine is heated an isomeric
3-pyroindaconitine seems to be formed.
The investigation shows that indaconitine is acetylbenzoylpseudo-
aconine. J. Chem. Soe., 87, p. 1620.
A new alkaloid, bikhaconitine, was extracted from Aconitum
spicatum by W. R. Dunstan and A. E. Andrews. The method of
extraction was the same as the one used for indaconitine (see pre-
ceeding paragraph). Bikhaconitine does not crystallize as readily
as the other “aconitines.” It is best purified by passing it through
the hydrobromide and adding water to its alcoholic solution. It is
soluble in alcohol, ether or chloroform but insoluble in water or
petroleum ether. When crystallized from alcohol and water and
dried at 85° it melts at 113—116°, when crystallized from ether it
melts at 119—123°. The formula of bikhaconitine is C36H51NO11, H2O
and its specific rotation is + 12.21° when anhydrous. It contains
six methoxyl groups. Several well crystallized salts of bikhaconitine
were prepared. The aurichloride is soluble in chloroform but insoluble
in water. The physiological action of bikhaconitine is similar to
that of the other aconitines
Bikhaconitine resembles pseudoaconitine in containing one acetyl
and one veratroyl group the separation of which may be effected in
two stages according to the equations:
6
1) C36H51NO.11 + HOg = C34 H49NO10 + CH3.0O2H
Bikhac Onitine. Veratroylbikhaconine.
2) C34H49NO10 + H2O = C25H41NOT + C9H1004
Bikhaconine. Veratric Acid.
The reaction represented by the first equation is best conducted
by heating the aqueous solution of the sulphate to 130° for seven
hours. The veratroylbikhaconine was purified by converting it into
its aurichloride which crystallizes well. The free alkaloid melts at 120°
to 125° and does not crystallize. Unlike veratroylpseudoaconine it
is dextrorotatory. Of the haloid salts only the hydriodide of vera-
troylbikhaconine could be obtained in crystalline form. The alkaloid
forms a crystalline aurichloride which is soluble in alcohol or chloro-
form.
The preparation of bikhaconine according to the second equation
is effected by means of alcoholic soda. Bikhaconine is amorphous
but forms crystalline salts. The aurichloride as it separates out at
first is amorphous but it soon becomes crystalline.
On heating bikhaconitine to 180° acetic acid is split off and a
new base, pyrobikhaconitine, is formed
Cae H51NO11 = C34H47NO9 + CH3.0O2H
Bikhaconitine. Pyrobikhaconitine.
The pyrobikhaconitine is best prepared by heating bikhaconitine
to 200° for ten minutes in a flask from which the air has been
exhausted. Neif her the alkaloid itself nor any of its salts could be
obtained in crystalline form. Journ. Chem. Soc., 87, p. 1636.
According to W. R. Dunstan and T. A. Henry the aconite group
of alkaloids can be divided chemically and physiologically into two
groups: (1) the “aconitine” group of very poisonous alkaloids
comprising, aconitine, japaconitine, pseudoaconitine, bikhaconitine
and indaconitine, and (2) the non-toxic group of “atisines” consisting
of atisine and palmatisine. The “aconitines” are diacyl esters of a
series of polyhydroxy bases containing four methoxyl groups (the
a comines). The toxic properties of the “aconitines” are almost com-
pletely abolished with the removal of the acetyl group.
It is probable that the aconitines are all derived from one com-
mon base having the formula, C21H86N or C21H84N.
OAC
/
Aconitine............................ C21 HºNor-owo,
OBZ
OAC
/
Japaconitine...................... C21 Hºnor- OMe)4.
OBZ
OAC
/
Indaconitine....................... C21H27NO2—(OMe)4.
N
OBZ
OAc
/
Pseudoaconitine................. C21 H27NO2—OMe
N
O.COC6H3(OMe)2
OAC
/
Bikhaconitine...................... C21H270N–(OMe)4
N,
O.COC6H3 (OMe)2
Journ. Chem. Soc., 87, p. 1650.
Aconitine.
E. P. Alvarez has devised the following color reaction for aconitine.
From 0.0005 to 0.002 gram of the alkaloid is warmed on the water-
bath with 5 to 10 drops of bromine, one or two drops of fuming
nitric acid are then added and the liquid evaporated to dryness. To
the yellow residue 0.5 to 1 c. c. of a saturated solution of potassium
hydroxide in alcohol is added and the liquid again evaporated to
dryness. On now adding to the cold residue 5 or 6 drops of a 10%
solution of copper sulphate an intense green color is developed.
* Gaz. Chim. Ital., 35, p. 11, 430.
The following color reactions of aconitine (pure amorphous) are
proposed by C. Reichard. On adding a little aconitine to glacial
phosphoric acid mixed with a drop of water and gently warming the
mixture dark violet stripes appear at first which on further heating
assume a mixed color of violet-brown-black. In this reaction meta-
phosphoric can be used instead of orthophosphoric acid.
8
A strong solution of antimony trichloride slightly acidulated
with hydrochloric acid is colored black by aconitine. The color is
not changed by strong hydrochloric acid.
If a transparent crystal of potassium ferrocyanide be added to
a solution of aconitine and sodium orthoarseniate in strong sulphuric
acid the solution assumes a blue color.
On warming a solution of aconitine in sulphuric acid the liquid
assumes a dark blue color.
A mixture of aconitine and ammonium molybdate is colored blue
by concentrated sulphuric acid. Ammonium persulphate changes the
blue color to a magnificent yellow particularly upon slight warming.
A mixture of aconitine and potassium dichromate is colored dark
green by strong sulphuric acid. The color is changed to blue or
green-blue by ammonium persulphate.
With mercurous nitrate aconitine gives a black precipitate.
On warming a mixture of aconitine, ammonium persulphate and
concentrated sulphuric acid a brown-black color is developed, but
the color disappears in a few minutes with the evolution of an ozone-
like Odor.
Aconitine does not reduce copper sulphate or copper oxychloride
and does not liberate iodine from potassium iodate.
With ferric chloride aconitine gives a colorless solution. If the
solution be evaporated to dryness and a drop of concentrated sul-
phuric acid added to the residue a dark brown color is developed.
Pharm. Centr.-H., 46, p. 479.
H. Schulze has investigated aconitine and its decomposition
product aconine. The formula of aconitine is either Caałł47NO.11 or
C34H45NO11. On heating aconitine with 20 times its amount of
water under a pressure of 6 or 7 atmospheres about 80% of the
theoretical yield of aconine was obtained. Free aconine, C25H41NO9,
is a white hygroscopic powder. Its melting point varies considerably
with the method of heating it. It forms a crystalline hydrobromide
containing one and a half molecules of water of crystallization. The
nitrate and the sulphate could not be obtained in crystalline form.
Neither formic aldehyde, nor hydroxylamine, nor phenylhydrazine
react with aconine, nor could a definite compound be obtained with
phenyl isocyanate.
Aconine contains one methylimide and four methoxyl groups.
9
Of the eleven oxygen atoms of aconitine three belong to free OH
groups, four are present in the form of CH3O groups, one belongs to
an OH group in which the H is replaced by an acetyl group and
one to an OH group in which the H is replaced by a benzoyl group.
As a conitine is acetyl benzoyl aconine there ought to be in
aconine 5 OH groups and 4 CH3O groups. The presence of 4 OH
groups could be shown by the formation of a tetracetyl aconine but
the fifth OH group could not be detected.
While aconine is a tertiary base it does not react with methyl
iodide or methyl sulphate.
As aconine is not easily affected by potassium permanganate in
presence of sulphuric acid there seem to be no double bindings in
this base. Apoth. Ztg., 20, p. 368.
Angostural Bases.
A Beckurts and G. Frerichs have investigated the alkaloids of
angostura, bark. By extracting the bark with ether a mixture of
crystalline and amorphous bases is obtained from which the crystal-
line bases are extracted by shaking the ethereal extract with a
solution of tartaric acid. The strongly basic crystalline alkaloids,
cusparine, galipine, cusparidine and galipidine form crystalline salts
with weak organic acids and separate out in crystalline form from
the etheral solution leaving the weakly basic amorphous bases in
the ether from which they can be extracted by means of dilute
hydrochloric acid.
The salts of the four crystalline alkaloids with the organic bases
are decomposed by hot water into free base and free acid, hence a
dilute solution of cusparine in dilute tartaric or acetic acid becomes
turbid when heated due to the separation of insoluble free cusparine.
From the solution of the tart rates of the crystalline bases the free
bases are obtained by mixing the solution with ether and ammonia
and slowly evaporating the ether. As the ether evaporates the
ethereal solution becomes heavier than the aqueous liquid and settles
at the bottom of the vessel in crystalline form.
Cusparine and galipidine constitute the largest part of the mix-
ture of the crystalline alkaloids, cusparidine and galipine being
present only in small quantities. The separation of the four crystal-
line alkaloids from each other was effected either by fractional
crystallization of the free bases from alcohol or by solution in dilute
10
sulphuric acid and fractional precipitation with sodium sulphate.
From the mixture of the four crystalline bases a small amount of a
fifth crystalline alkaloid was obtained in colorless needles insoluble
in ether.
The mixture of amorphous bases forms an oily liquid from which
low boiling petroleum ether extracts another crystalline alkaloid
cuspareine. Cuspareine can also be obtained by adding a solution
of picric acid in ligroin to a ligroin solution of the amorphous bases.
Cuspareine being even less basic than the amorphous bases remains
in the ligroin solution whereas the amorphous bases are precipitated
as picrates. Cuspareine has the formula, Cai H36N2O5, melts at 54°
and does not form any salts with acids. It is soluble in dilute
hydrochloric acid but is extracted from the acid solution by repeated
shaking with ether. On evaporating the acid solution the free base
remains as a varnish. Cuspareine is very stable at high temperatures
distilling unchanged under ordinary pressure at about 300°.
A solution of cuspareine in dilute sulphuric acid is colored red by
oxidizing agents.
The amorphous bases form a thin oily liquid and distil without
decomposition. From their solution in dilute hydrochloric acid they
are left in the free condition upon evaporation of the solvent.
The previously established formula of cusparine, C20H19NO3, was
found to be correct. The alkaloid is a tertiary base and contains
one CH3O group. When perfectly pure it remains white when covered
with acidulated water, a yellow color indicates the presence of
galipine.
Cusparine nitrate, C20H19NO3.HNO3 + 1%H20 was obtained by
neutralizing an alcoholic solution of cusparine with nitric acid. The
nitrate becomes dark on exposure to the air. Cusparine dichromate
was obtained by adding a solution of potassium dichromate to a
Solution of the base in dilute acetic acid. The dichromate becomes
brown on exposure to the air. For the estimation of chromium in
this Salt the chromic acid was reduced by alcohol and after removal
of the cusparine as a difficultly soluble hydrochloride the chromium
precipitated by ammonia. Cusparine acetate loses all its acid when
its Solution is evaporated to dryness.
On treating a dilute solution of cusparine hydrochloride with
the theoretical amount of bromine water and then adding ammonia
11
monobrom-cusparine was obtained in monoclinic crystals melting at
91°. The monobrom-cusparine, C20H1's Brx 03 forms a hydrochloride
which is soluble in hot water.
On adding excess of bromine water to a solution of cusparine
hydrobromide bromcusparine tetrabromide, C20H18 BryO3. Brá, was
Obtained. When washed with cold absolute alcohol the tetrabromide
is converted into bromcusparine tribromide, C20H18 Brn O3. Bræ, and
when heated to 105° it is changed into bromcusparine dibromide,
C20H18 Brn O3. Br2. From a solution of the tetrabromide, tribromide
or dibromide in warm alcohol bromcusparine, C20H1s Brx O2,
separates out on cooling. The additive bromine can be removed
from the tetrabromide by reducing it with zinc and sulphuric acid
or boiling with a one percent solution of potassium hydroxide in
alcohol or treating the tetrabromide with sulphuretted hydrogen.
By the action of bromine upon cusparine in chloroformic solution
the above dibromide is formed and in glacial acetic acid the above
tribromide is formed.
A dichlorcusparine was prepared by treating a solution of
cusparine in dilute acetic acid with sodium hypochlorite.
Wagner's reagent converts cusparine hydrochloride into cusparine
hydriodide diiodide, C20H19NO3.H.I.I.2, which can be recrystallized
from alcohol without decomposition.
Cusparine is not effected by hot dilute nitric acid, but strong hot
nitric acid changes it into the nitrate of a nitrobase. With methyl
iodide and ethyl iodide cusparine forms addition products which are
converted by potassium hydroxide into the corresponding alkyl-
cusparines.
The hydrochloride of ethyl cusparine, C20H1s(C2H5)NO3.HCl, can-
not be obtained by neutralizing ethyl cusparine with hot hydro-
chloric acid as on cooling unchanged ethyl cusparine separates out,
but the Salt can be obtained by saturating a chloroformic solution
of cusparine with hydrochloric acid gas.
Ethyl cusparine forms a chloroplatinate and a chloraurate.
Attempts to bring cusparine into reaction with methylene bromide
or ethylene bronnide were not successful. No combination of cusparine
with chloroform, iodoform or chloracetone could be obtained nor
12
could a benzoyl derivative of the alkaloid be made by heating the
base for six hours with benzoyl chloride. -
When cusparine is melted with potassium hydroxide it is at first
converted into a new base, pyrocusparine, C18H15NO3, and then into
protocatechuic acid. The pyrocusparine is formed by the action- of
heat alone, which is shown by the fact that the same pyrocusparine
is formed by heating cusparine with urea to 220–250°. In the
fusion with potassium hydroxide there is formed besides pyro-
cusparine another base having a much lower melting point, than
pyrocusparine. The formation of protocatechuic acid from cusparine
which contains one CH3O group but no OH groups would seem to
indicate that the protocatechuic acid is linked to the rest of the
molecule of the alkaloid by one of the OH groups of the acid while
the other OH group of the acid contains the CH3 group instead of
hydrogen.
Galipidine, C19H19NO3, forms white crystals which become yellow
in the air. The alkaloid forms colorless salts with acids when per-
fectly free from galipine. The complete removal of galipine from
galipidine can be effected by treating the latter with nascent hydrogen.
On adding an excess of dilute sulphuric acid to a solution of galipi-
dine hidrochloride a crystalline precipitate is formed which consists
of a mixture of the neutral and the acid sulphates. The acid sul-
phate of galipidine, C19H19NO3.H2SO4 was obtained by adding excess
of dilute sulphuric acid to an alcoholic solution of galipidine and
concentrating the liquid.
A solution of galipidine in strong sulphuric acid is colored violet-
red by potassium dichromate. Excess of the dichromate destroys
the color. On pouring the reaction product into water, dissolving
the resinous mass which separates out in ammonia and reprecipitat-
tº.
ing with hydrochloric acid a crystalline substance was obtained.
By fusion with alkali galipidine yields protocatechuic acid. On
adding excess of bromine water to a solution of galipidine hydro-
bromide a hydrobromide pentabromide of galipidine is precipitated.
The pentabromide When washed with cold absolute alcohol loses
four atoms of bromine and is converted into galipidine hydrobromide
monobromide, C19H19NO3.H.Br. Br. When heated to 105° the penta-
bromide is converted into a hydrobromide dibromide C19H19NOs.
HBr, Bra. -
13
With methyliodide at 100° galipidine forms an iodomethylate,
C19H19NO.CH3I. The free ammonium base corresponding to the
iodomethylate could not be isolated but was converted into the
platinum and gold salts.
When galipidine methyliodide is treated with potassium hydroxide
methyl galipidine, C19H1s(CH3)NO3, is formed.
Galipidine iodoethylate, C19H19NO3.C2 HäI was prepared by heat-
ing the components for 12 hours to 100°. The iodoethylate contains
one molecule water of crystallization and melts at 102° to a turbid
liquid becoming transparent only at 140–142°. The free ammonium
base corresponding to the iodoethylate was not isolated but was
converted into a chloraurate.
No addition products could be obtained from galipidine and
methylene iodide, ethylene bromide or ethylene iodide.
Arch. Pharm., 243, p. 470.
Aporeine.
W. Pavesi has isolated a new all-aloid from Papaver Dubium and
named it aporein. The method used for the isolation of the alkaloid
was the same as the one used by O. Hesse for the preparation of
rheadine. The alkaloid is amorphous and slightly yellowish. Hydro-
chloric acid (10%) converts it into a crystalline shining mass. By
recrystallization from ether, chloroform or petroleum ether the
alkaloid can be obtained in microscopic plates. With a mixture of
sulphuric and nitric acids the alkaloid gives a violet color which
soon changes to brown and then to yellow. Froehde's reagent
colors it at first grayish blue, then successively green, brown and
yellow. With formic aldehyde and concentrated sulphuric acid a
succession of green, blue and black colors is obtained.
Placed on the tongue aporeine produces first a burning and then
a benumbing sensation.
In physiological activity it resembles thebaine.
Chem. Centr.-B., 76, 1, p. 827.
Berberine.
According to J. Gadamer berberine exists in two modifications:
8->
as a true ammonium base (I) and as a pseudoammonium base (II)
or (III).
14
O——CH2
|
O.CH3 |
* | *
cº-o-º/ `
| |N
| |
Nº N ºch,
Berberinium Hydroxide.
(I)
()——CH2
º
º
H|N |CH2
/ N N /
(). CH3
Berberinal (Aldehyde Form).
(II)
N / N /N /
/ N / N /
(SH CH2
|
() H
Berberinal (Carbinol Form).
(III)
1.5
When the theoretical amount of barium hydroxide is added to a
solution of berberine sulphate, berberinium hydroxide is formed which
remains in solution giving the latter a strong alkaline reaction. If
the solution of berberinium hydroxide be evaporated the alkaline
reaction gradually disappears the ammonium base changing to the
pseudo base (II) or (III). As the residue is not completely soluble
in dilute acids part of the base must undergo some deeper decom-
position in this transformation of the ammonium form to the pseudo
form. It is therefore impossible to obtain berberinium hydroxide in
solid form, and the substances which were considered as pure berbe-
rine by previous investigators must have been derivatives or decom-
position products of berberine. The same berberinium hydroxide is
formed when berberine-acetone is treated with superheated steam,
the acetone distilling over with the steam. Berberinium hydroxide
is also formed when berberinal is heated with water, and the change
of the pseudo form to the ammonium form can be noticed by the
strongly alkaline reaction which the liquid gradually assumes. Hence
berberinium hydroxide differs from most other ammonium bases
capable of assuming a pseudo form in that the reaction in the case
of berberine is to some extent reversible.
If excess of sodium hydroxide be added to a solution of ber-
berinium hydroxide the liquid becomes almost colorless and ber-
berinal is precipitated. On shaking the liquid with ether the ber-
berinal is extracted and on keeping the ether in a cool place the
base separates out in yellow needles which slightly darken on stand-
ing. Berberinal is insoluble in cold water but dissolves in hot water
to a brownish-yellow liquid of a strong alkaline reaction and does
not separate out on cooling (change to ammonium form). It is
quite stable in the air but is immediately converted by acids into
salts of quaternary berberinium hydroxide. It contains no water of
crystallization and has the formula, C20H19NO5. The transforination
of berberinal into salts of berberinium hydroxide is accompanied
with the elimination of water:
CHO CH
/ /.
/ Y? -- ſt /
C19H1701 N + HCl --- C19H1704 . + II 2 O
NH N.C.
Berberinal. Berberine Chloride.
16
The presence of an aldehyde group in berberinal was shown by
the three following reactions:
1. Alkalies convert two molecules of berberinal into One mole-
cule of dihydroberberine, C20H19NO4, and one molecule of oxyber-
berine, C20H17NO5. In this reaction berberinal resembles aromatic
aldehydes of which two molecules are generally converted by alka-
lies into one molecule alcohol and one molecule acid, but the alcohol
and the acid formed from berberinal immediately lose water and the
ring is closed:
/ CH2, OH / CH2
/ t -- / |
C19H1704 N ——) C19H1704 N |
>] NH N N
ycho- Dihydroberberine.
C19H1704
Berberinal NH /
-/ 2 CO. OH / C()
º -——X Cohºo.(
Oxyberberine.
The oxyberberine was separated from the dihydroberberine and
the berberine by means of dilute hydrochloric acid which dissolves
only the last two, and the dihydroberberine was separated from the
berberine by means of ammonia which precipitates only dihydro-
berberine.
2. Berberinal forms an oxime when treated with hydroxylamine
in ethereal solution.
3. Berberinal can be condensed with para-dimethyl-amido-aniline
to berberinal-dimethyl-amido-anilid
CH — N.C6H4...N (CH3)2
/
C19H1704 z
N
*NNH
The presence of an NH group in berberinal could not be proved,
As the constitution of berberinal is similar to that of cotarnine
it was expected that when berberinal is treated with methyl iodide
there would be formed an iodomethylate of the methylated base to.
gether with the hydriodide of the base.
17
/CHO
208 Hoos. + 2CH3T =
NCH2.0H2.N.H.CH3
Cotarnine.
/CHO / CH = N (CH3)I
chok + Cahoos' | + H2O
NCH2. CH2.N(CH3)3][ N CH 2. CH2
But experiment showed that when berberinal is treated with
methyl iodide only berberine iodide is formed. It is possible that at
first the reaction is similar to that of cotarnine
2^CHO
2C19H110.3 + 2CH3 I = -
NNH
Berberinal.
/CHO /CH
Cohºo.( + Cohºo.( | + H2O
\schoºl NN.I
Iodomethylate of Berberine
Methyl berberinal. Iodide.
..but that the water formed in the first stage of the reaction converts
the iodomethylate of methylberberinal into berberine iodide
/ CHIO / CH
+ H2O = Cohºo, + 2CH, OH
O.
\schoºl \R.I
The aldehyde group in berberinal would therefore seem to be less
stable than the same group in cotarnine. This would be in accord
with the fact that berberinal oxime is also less stable than cotarning
Oxime.
Attempts to prove the presence of an NH group in berberinal by
making acyl derivatives were also unsuccessful. On treating ber-
berinal with benzoyl chloride in presence of alkali only berberine
chloride was obtained. The results were nearly the same even when
silver nitrate was added to the benzoylating mixture.
With regard to some derivatives of berberine the author derives
the acetone compound, the chloroform compound, the alcoholate,
the alkyl halides and the cyanide from the carbinol form (III) of
C19H17
18
berberinal in which the OH group is replaced by some radical with
the elimination of water. The general formula of these compounds
is therefore
/ CH-R
ºl
in which R stands for one of the following groups: CH2CO.CH3,
CCl3, OC2H5, CH2I, C2H4 I, C5H10I or CN. Such a formula would ex-
plain the instability of these alkyl halides. +
On the other hand the polysulphides of Schmidt and Gaze the
author derives from the ammonium form of the base (1)
/CH /CH
Cºhºo.( | Sé Cohºok | S5
\N N
Berberine Hexasulphide. B. Pentasulphide.
The acid sulphite of berberine made by Perkins the author derives
from the aldehyde form (II). It is supposed that at first an alde-
hyde sulphurous acid is formed which by the loss of H2O is converted
into an inner salt :
SO2.OH
/
/(HO / CIH.OH Jºhsoon
/ / t
C19H1704 —). C19H1 704 —). C19H1704 ——)
NH \s H NN
/ CH.SO2
N
—X C19H17 º º /
Berberine acid sulphite.
This formula would explain why the acid sulphite crystallizes
out unchanged from a dilute solution of potassium carbonate which
would convert a true bisulphite into neutral Sulphite.
Arch. Pharm., 243, p. 31.
M. Freund and F. Mayer find that when methyl dihydroberberine
is reduced electrolytically it is changed to methyl tetrahydrober-
berine.
!
19
*—ºn.
|
/~ &
CH3O |
CE . . .
a.o.º."
——X
N |
| |
HC / N / N / CH2
N/ C N / N/
CH CH CH2
|
f CH3
Methyl dihydroberberine.
*—ºn.
/\ }
cHº gº. %.
choſ N / N / N/
| | x|NH
| / N x JN 'oh,
Nº. N / N/
CH CH2
(H.
Methyl tetrahydroberberine.
As methyl tetrahydroberberine contains two asymmetric carbon
atoms it ought to exist in two isomeric forms each of which is
made up of a pair of mirror images.
The methyl tetrahydroberberine has a very light yellow color.
O.CH3
// N
/ N().CH3
O.CH3 CH2
|
choºl \º
Corydaline.
20
The structure of methyl tetrahydroberberine is similar to that
of corydaline.
Caffeine.
The color reactions of caffeine and theobromine were studied by
C. Reichard. On adding to caffeine or theobromine a mixture of 2
parts nitric acid and 5 parts hydrochloric acid, evaporating the
mixture to dryness and then heating the residue still further a
magnificent egg-yellow color is developed which on further heating
passes through several colors to brick-red, purple-red and brown.
f
Ammonia does not change the yellow color to purple (as in the
murexide reaction) nor does it intensify appreciably the red end
color. The red color disappears on cooling but reappears on warm-
ing the residue. The addition of water changes the red color to
yellow but on evaporation of the water and heating the red color
again makes it appearence. Concentrated sulphuric acid gradually
destroys the red color. Concentrated nitric acid alone does not
produce the above color reaction, but a mixture of potassium
chlorate or ammonium persulphate and hydrochloric acid gives the
Same reaction as a qua regia.
A mixture of mercuric chloride and caffeine is gradually colored
yellow by hydrochloric acid. Theobromine remains unchanged under
these conditions.
A mixture of theobromine and mercurous nitrate becomes black
upon addition of water. Caffeine is not affected by this reagent.
On moistening a mixture of copper oxychloride (Cu2Cl2O) and
either caffeine or theobromine with ammonia a deep blue color is
developed. On evaporating the liquid to dryness and adding hydro-
chloric acid a light green solution is obtained. When this solution
is evaporated to dryness a light green residue is obtained in the
case of theobromine and a dark green residue in the case of caffeine.
A mixture of caffeine or theobromine with potassium ferrocyanide
is colored greenish-blue by cold hydrochloric acid and gray-blue by
cold concentrated sulphuric acid.
A mixture of potassium dichromate and hydrochloric acid colors
either of the alkaloids intensely yellow. On evaporating to dryness
and adding to the residue concentrated sulphuric acid a violet-blue
color is developed which soon changes to green-blue or dark green.
A mixture of eaffeine or theobromine with ammonium hepta-
2ſ.
molybdate is colored intensely blue by hot hydrochloric acid; the
blue residue is colored by a mixture of sulphuric acid and ammonium
persulphate at first reddish-yellow and then yellow.
A mixture of either of the alkaloids with titanic acid is colored
greenish-blue by cold concentrated sulphuric acid. The color changes
upon heating to blue-violet.
A mixture of either of the alkaloids and sodium vana.date is
colored dark brown by concentrated sulphuric acid.
A mixture of either of the alkaloids and a-nitroso-8-naphtol dis-
solves in cold hydrochloric acid (25%) with a dirty green color; on
evaporating the solution to dryness the residue is grayish-white in
case of theobromine and in case of caffeine dark green with brown-
red spots. gº
On evaporating a solution of either of the alkaloids in concen-
trated potassium sulphocyanate to dryness and taking up the residue
with warm hydrochloric acid a yellow color is developed.
Either of the alkaloids is colored yellow by sodium iodate and
hydrochloric acid. Concentrated sulphuric acid changes the yellow
color to brown. Pharm. Centr.-H., 46, p. 846.
Calycanthine.
The alkaloid calycanthine obtained from Calycanthus glaucus
was investigated by H. M. Gordin. The alkaloid was isolated from the
drug by the following method : The seeds were coarsely ground and
extracted with petroleum ether to remove oil. The extracted mark
was reduced to a fine powder and exhausted with hot alcohol. After
distilling off the alcohol from the tincture the residue was dissolved
in dilute acid, the solution filtered and the alkaloid precipitated by
sodium hydroxide. For purification the base was converted into
the sulphate which is very difficultly soluble in alcohol and almost
completely insoluble in acetone and the free base again precipitated
from the aqueous solution of the sulphate by alkali. From a mix-
ture of acetone and water calycanthine crystallizes with half a mole-
cule of water of crystallization. It has the formula, C11H14N2.%H2O.
It forms crystalline salts with most acids except tartaric acid. The
acetate continually loses acetic acid. Calycanthine is a weak mono-
acid base and forms a chloraurate having the composition,
3(C11H14N2.HCl AuCla) + 2C11H14N2. HCl + 2%H2O.
22
On dissolving the chloraurate in alcohol and adding ether to the
solution, calycanthine hydrochloride crystallizes out. The alkaloid
contains a CH3.N group and is a secondary base forming a nitros-
amine when treated with nitrous acid. The alkaloid gives some
characteristic color reactions chief among which is a deep purple
with gold chloride in presence of sodium carbonate. Physiological
tests by Cushny showed that “in mamals the alkaloid acts as a
stimulant to the spinal chord and as a depressant to the heart. In
frogs it has, in addition, a weak, curare-like action on the termina-
tions of the motor nerves. The symptons are so similar to those
described in cattle from poisoning with calycanthus that there can
be no doubt that the alkaloid is the chief poisonous constituent.”
J. Am. Chem. Soc., 1905, pp. 144 and 1418.
Cinchona Alkaloids.
A. Christensen continues his inves igations of the bromine deriv-
atives of the cinchona bases.
On treating a solution of cinchonidine or cinchonine in acetic
acid (80%) with bromine and hydrobromic acid, two isomeric
dibromides are obtained from each alkaloid : a- and 8-cinchonidine
dibromide and a- and 8-cinchonine dil)romide respectively.
The two cinchonidine dibromides were separated from each other
by converting them into the nitrates, the nitrate of the 3-compound
being much less soluble in water than the nitrate of the a-compound.
The two cinchonine dibromides were separated from each other
by means of their hydrobromides.
When treated with alcoholic potassium hydroxide a-cinchonidine
dibromide loses two molecules of hydrobromic acid and is converted
into dehydrocinchonidine, C19H2ON2O. When this dehydrocinchonidine
is treated with bromine and hydrobromic acid in acetic acid solution
it is converted into the perbromide of dibromcinchonidine hydro-
bromide, C19H20 Br2N2O.2H Br. Brø, from which free dibromcinchonidine
can be obtained by means of sulphurous acid and ammonia.
When boiled with alcohol a-cinchonidine dibromide loses only a
trace of hydrobromic acid. It forms a nitrate, a hydrobromide, a
perbromide and a sulphate.
Concentrated sulphuric acid converts a-cinchonidine dibromide
into a sulphonic acid, C19H21(SO3H) Br2N2O, which forms salts both
with acids and alkalies. When the sulphonic acid is heated with
23
alcoholic potassium hydroxide hydrobromic acid is split off but no
sulphuric acid. Hence the compound is a true sulphonic acid, not
an ester.
When 3-cinchonidine dibromide is heated with alcohol it loses
one molecule hydrobromic acid and is converted into monobrom-
cinchonidine, C19H21 Brn 20. Alcoholic potassium hydroxide converts
6-cinchonidine dibromide into dehydrocinchonidine, C19H2ON2O.
The dehydrocinchonidine and the monobromcinchonidine obtained
from 8-cinchonidine dibromide are identical with the dehydrocincho-
nidine and the monobromcinchonidine obtained from a-cinchonidine.
Hence the isomerism of the two cinchonidine dibromides must be of
the same nature as the isomerism of ethylene bromide and ethylidene
bromide.
8-cinchonidine dibromide forms a nitrate, a hydrobromide and
a perbromide containing four atoms of additive bromine (the per-
bromide of a-cinchonidine dibromide contains only two atoms of
additive bromine), a normal sulphate, (C19H22Brz N2O)2PH2SO4 and
a tetrasulphate, C19H22 Br2N2O.2H2SO4.
A sulphonic acid of 8 cinchonidine dibromide can be obtained
either by digesting the base with sulphuric acid or by heating its
sulphate to 100°.
The two dibromides of cinchonine also differ from each other in
the same way as the two dibromides of cinchonidine which is shown
by the fact that the dehydrocinchonine and the monobromcinchonine
obtained either from a- or 8-cinchonine dibromide are identical in
both cases. Journ. pr. Chem., 71, p. 1.
Cinchonine.
P. Rabe and K. Ritter show that the nitrile of methyl mero-
quinene can be obtained in good yield by treating isonitroso methyl
cinchotoxine with phosphorus pentachloride and decomposing the
resulting product with water.
CH2——CH-CH-CH : CH2 CH2—CH-CH-CH : CH2
|
CH2 CH2
|
º CH2 = CN º + Colig-CO2H
hos- N.CH3–UH2 N.CH3–0H2
C9HoN
ISOnitroso methyl cinchotoxine. Nitrile of methyl meroduinene. Cinchoninic acid.
24
. The methyl cinchotoxine was obtained by boiling cinchonine
iodomethylate with glacial acetic acid in presence of sodium acetate.
The methyl cinchotoxine was then converted into isonitroso methyl
cinchotoxine by the method of Rhode and Schwab (Ber. Dtsch. chem.
Gesch., 38, p. 306). It is advisable to pass CO2 through the liquid
untill the complete separation of the base has been effected. The
isonitroso compound is at first oily but becomes crystalline by
vaccination and rubbing with a glass rod.
The decomposition of isonitroso methyl cinchotoxine into the
nitrile of methyl meroguinene and cinchoninic acid was carried out
by treating a cooled solution of the isonitroso compound in chloro-
form with powdered phosphorus pentachloride, throwing the product
into ice water and, after making the liquid alkaline, distilling over
the nitrile with steam.
The nitrile, a colorless liquid boiling at 252—255°, is a strong
base of a piperidine-like odor and is volatile with steam. An iodo-
methylate, a picrolonate, a picrate and a chloraurate of the nitrile
were prepared. • º
The formation of cinchoninic acid in the decomposition of iso-
nitroso methyl cinchotoxine was shown by treating the acid liquid
obtained after the reaction with phosphorus pentachloride with
barium hydroxide and, after removing the excess of hydroxide by CO2,
converting the barium salt into the copper salt. The cinchoninic
acid was then obtained from the copper salt by decomposing the
salt with sulphuretted hydrogen.
Ber. Dtsch. chem. Ges., 38, p. 2770.
K. Kaas finds that a-isopseudocinchonicine which is formed by
heating the acid sulphate of a-isocinchonine is a secondary base and
contains a CO group. The secondary nature of the compound was
shown by treating it with methyl iodide which converts it into the
hydriodide of an N-methyl derivative. The presence of an N-methyl
group was shown by Herzig and Meyers method. That the relation
of a-isopseudocinch Onicine to 0-isocinchonine is the same as that of
cinchonicine to cinchonine was also shown by the fact that just as
N-methyl cinchonicine obtained by methylating cinchonicine is
identical with the compound obtained by splitting off hydriodic acid
from cinchonine iodomethylate in the same way N-methyl a-isopseudo-
cinchomicine is identical with the compound obtained by splitting off
25
hydriodic acid from the iodomethylate of a-isocinchonine. As the
conversion of cinchonine into cinchonicine consists in the change of
a tertiary base containing an OH group to a secondary base con-
taining a CO group a-isopseudocinchonicine must also contain a CO
group (comp. Monatsh. f. Chem., 1904, 1145).
When a-isopseudocinchonicine is treated with chlorine it takes
up one molecule of hydrochloric acid (instead of one molecule of
chlorine as might be expected). In the same way when 3-isocinchonine
is treated with bromine the base takes up one molecule of hydro-
bromic acid. This makes it probable that like cinchonine these two
bases (a-isopseudocinchonicine and 3-isocinchonicine) contain a vinyl
group. (Monatsh. f. Chem., 26, p. 119.
Cinchotoxine.
G. Rohde and G. Schwab find that contrary to the statement of
Brunner and Fussenegger the reaction between isonitroso cinchotoxine
and methyl iodide in chloroformic solution is perfectly normal the
following compounds being formed : the iodomethylate of isonitroso-
methyl-cinchotoxine, the hydriodide of isonitroso-methyl-cinchotoxine
and the hydriodide of isonitroso cinchotoxine (compare Ber. Dtsch.
chem. Ges., 1900, 3221, 3234).
C.CH3 C.CH3
HC2 CH.CH = CH2 H2O CH.CH=CH2
CO yº
* /a: H2CX /*
NH N.CH3
NC9Ho.O. = N.OH N('9EI6.0= N.OH

ISO nitroso cinchotoxine. ISOnitroso methyl cinchotoxine.
26
C.CH3
H20. CH.CH = CH2
CO
H20 × CH2
N(CH3)2][
NC9H8.0 = N.OH
Idomethyla, te of isonitrosomethylcinchotoxine.
This was shown by separating these compounds from each other
and identifying them by a comparison with the compounds obtained
separately and by such methods as leave no doubt about the nature
of the substances. The iodomethylate of isonitroso methyl cincho-
toxine was separated from the two hydriodides by means of sodium
carbonate and the hydriodides from each other by means of
nitrous acid which precipitates the secondary base as an insoluble
nitrosamine.
If in the reaction with methyl iodide isonitrosoquinotoxine be
taken instead of isonitroso cinchotoxine the corresponding quino-
toxine compounds are formed.
*
C.CH3

/N
H2O CH.CH = CH2
CO
/
H2CX CH2
_^ N/
NH
NC6H5 (CH3O).C+ N.OH
Isonitrosoquinotoxine.
The separate methods by which these compounds were prepared
were as follows:
The isonitroso cinchotoxine itself was prepared by Brunner's
method (loc. cit.) but the liberation of the free base from its mono-
27
hydrochloride which is first formed in this method was carried out
by means of sodium methylate dissolved in absolute alcohol.
The isonitroso methyl cinchotoxine was prepared by converting
cinchonine into cinchonine iodomethylate, then splitting off hydriodic
acid by boiling the iodomethylate with sodium hydroxide in iron
vessels (glass vessels broke) for three days and treating the result-
ing methyl cinchotoxine with amyl nitrite in presence of sodium
ethylate dissolved in absolute alcohol. On treating the product of
the reaction between amyl nitrite and methyl cinchotoxine with
excess of carbon dioxide in aqueous solution the free isonitroso
methyl cinchotoxine separates out at first as a resinous mass which
soon redissolves presumably as a carbonate. When this solution is
set aside for some time or a current of air is drawn through it the
isonitroso methyl cinchotoxine separates out again but this time in
crystalline form. It was purified by dissolving it in sufficient hydro-
chloric acid (20%) to form the dihydrochloride and then adding an
amount of sodium acetate equivalent to the amount of acid taken.
Under these conditions the monohydrochloride separates out as an
oily liquid which after some time changes to a crystalline mass. It
crystallizes from a mixture of alcohol and chloroform in glassy
crystals containing chloroform of crystallization which cannot be
removed by heat without decomposition of the hydrochloride. The
chloroform was removed by boiling the finely powdered salt with
ethyl acetate. From this hydrochloride the free isonitroso methyl
cinchotoxine was obtained by adding the theoretical amount of
sodium ethylate in alcoholic solution.
The monohydriodide of isonitroso methyl cinchotoxine was pre-
pared by the same method as the monohydrochloride but substitut-
ing hydriodic for hydrochloric acid. Like the hydrochloride the
hydriodide crystallizes from alcohol-chloroform in crystals containing
chloroform of crystallization which can be removed by boiling the
Salt with ethyl acetate. The hydriodide is precipitated from its
Solution by alkaline carbonates and is soluble in excess of fixed
alkali forming an alkaline salt.
The iodomethylate of isonitroso methyl cinchotoxine was pre-
pared by treating the isonitroso methyl cinchotoxine with the
theoretical amount of methyl iodide in chloroformic solution.
According to the rapidity of heating it the iodomethylate melts
between 228° to 235°. On exposure to the air the iodomethylate
28
becomes grayish white and assumes a porcelain-like appearance.
Treated with sodium ethylate the iodomethylate forms a sodium
Salt.
The monohydriodide of isonitroso cinchotoxine was prepared by
dissolving the free base in sufficient hydriodic acid (20%) to form a
dihydriodide and then adding a slight excess of sodium acetate.
The monohydriodide separates out partly crystalline and partly as
a brown oily liquid which becomes crystalline in a few days. When
heated it melts at 85°, then solidifies and melts again at 210°.
Derivatives of quinotoxine. When isonitroso quinotoxine is
treated with methyl iodide the following compounds are formed :
the hydriodide of isonitrosoquinotoxine, the hydriodide of isonitroso
methyl quinotoxine and the iodomethylate of isonitroso methyl
quinotoxine. These compounds were separated from each other and
identified by the same methods as were used for the separation and
identification of the corresponding cinchotoxine compounds.
The preparation of each of the derivatives of quinotoxine
separately was carried out as follows: The isonitrosoquinotoxine
itself was prepared by a method similar to the one used for the
preparation of isonitrosocinchotoxine, but as both the free isonitroso
quinotoxine and its monohydrochloride are quite soluble in water
the reaction product was shaken out with amyl alcohol and the
latter then shaken out with the theoretical amount of hydrochloric
acid (20%). On adding excess of sodium acetate the monohydro-
chloride of isonitroso quinotoxine separates out as an oily liquid
which soon becomes crystalline. From the monohydrochloride the
free isonitroso quinotoxine was obtained by dissolving the salt in
Sodium hydroxide and then passing a current of carbon dioxide into
the solution.
The monohydriodide of isonitroso quinotoxine was made by the
same method that was used for the preparation of the corresponding
cinchotoxine compound. The hydriodide melts at 102–1059 but
after resolidification the melting point is 217°.
The isonitroso methyl quinotoxine was made by the same method
as the corresponding cinchotoxine compound. The crystals of iso-
nitroso methyl quinotoxine when crystallized from benzol contain
benzol of crystallization and melt at 69–71°. The benzol can be
removed by boiling the base first with petroleum ether and then with
ligroin. After removal of the benzol the base melts at 1569.
• 29
By methods similar to those which were used for the preparation
of the corresponding cinchotoxine compounds the monohydriodide
and the iodomethylate of isonitroso methyl quinotoxine were pre-
pared. The iodomethylate crystallizes in two forms: in needles and
warts. On standing the first form changes to the second. Both
forms melt at 163°. Ber. Dtsch. chem. Ges., 38, p. 306.
Codeine.
E. Wongerichten and C. Weilinger prove that in nitro codeine the
NO2 group is not attached to the “bridge” carbon atoms but is in
the diphenyl nucleus of the phenanthrene complex. This was shown
as follows: When nitro codeine is converted into the iodomethylate
of diacetyl amido codeine and this compound treated with silver
acetate and acetic anhydride diacetyl — or possibly triacetyl amido-
methyl morphol is formed which upon oxidation is converted into
an Orthoquinone still containing the nitrogen atom of the nitro
group of nitro codeine. But as in this Orthoquinone the two “bridge”
carbon atoms being present as CO groups cannot be linked to the
nitrogen atom, the NO2 group in nitro codeine also cannot be linked
to one of these carbon atoms.
Ber. Dtsch. chem. Ges., 38, p. 1959.
Coniceine.
J. V. Braun and A. Steindorff have made some investigations
of Y-coniceine. According to von Lipp (Ann. d. Chem., 1896, 173)
tetrahydropicoline (I) cannot be benzoylated nor does nitrous acid
form with it a nitrosamine
CH2
/ N
H2O/ NCH
| |
|
| i
H2CN / C.CH3
N /
NH
Tetrohydropicoline.
(I)
In both reactions the ring is split open giving in the benzoylation
benzoyl amido butyl methyl ketone, C6H5OO. NH. (CH2)4.O.O.CHs, and
with nitrous acid acetyl butyl alcohol, HO. (CH2)4.(CH3.0O). Accord-
ing to Wallach (Ann. d. Chem., 39, 28; 319, 104) the unsaturated
30
cyclic base obtained from methyl heptenylamine also behaves ab-
normally towards reagents: With benzyl chloride a compound is
obtained containing one molecule water of more than is required by a
benzoyl derivative and with nitrous acid an unsaturated Open chain
ketone is formed. According to von Lipp and Widmann even water
alone splits open the ring of N-methyl tetrahydropicoline (II) form-
ing methyl amino butyl methyl ketone. They assume that the easy
opening of the tetrahydropyridine ring is due to the presence of an
ethylene binding next to the nitrogen atom.
CH2 CH2
/ N / N
H2C/ SCII H2C/ NCH
| |
H2CN / C.CH3 H2CN / C.C3H7
N / N /
N.CH3 NH
N-Methyltetrahydropicoline. Y-Coniceine.
(II)
The authors’ experience with Y-coniceine seems to corroborate this
assumption.
This base was found by several investigators to behave ab-
normally towards exhaustive methylation. Instead of exchanging
the imido hydrogen for two methyl groups and one halogen atom
as is the case with piperidine or coniine, Y-coniceine takes up one
molecule of methyl alcohol giving a quaternary compound having
the formula, Cs H 14 N(CH3)3.O.H.C), and the ammonium base corre-
sponding to this quaternary compound upon distillation gives a
mixture of an oxygen-containing amine, C8H15ON(CH3)2, and an
oxygen-free ketone, Cs H 140, instead of an unsaturated tertiary base
as is the case with piperidine or coniine. When Y-coniceine is treated
with benzoyl chloride one molecule of water is taken up and an open
chain benzoyl-4-aminobutyl propyl ketone, C6H500. NH. (CH2)4.CO.-
CH2.0H 2.0 HA, is formed. Nitrous acid converts Y-coniceine into a
nitrogen free compound, C8H140, and with benzaldehyde the base
combines without the elimination of water.
The preparation of benzoyl-4-amino butyl propyl ketone was
carried out by benzoylating Y coniceine by Schotten-Baumann’s
method and the presence of a ketone group in the resulting com-
pound was shown by converting it into a phenylsemicarbazone.
31
On substituting anisoyl chloride for benzoyl chloride in the
benzoylation of r-coniceine, anisoyl-4-amino butyl propyl ketone,
(CH3O) Co H4CO.NH. (CH2)4.0O.C3H7, was obtained again showing
that a molecule of water is taken up in the reaction. The presence
of a ketone group in the anisoyl derivative was shown by converting
it into an oxime and a semicarbazone.
On heating the benzoyl-4-amino butyl propyl ketone to 120°
with hydrochloric acid the ketone is reconverted into Y-coniceine
which can be identified by its gold and platinum salts as well as by
Other characteristic reactions.
The authors find that the green-reddish color developed by
warming r-coniceine with hydrochloric acid is given only by such
Y-coniceine as is obtained by distilling the base under ordinary
pressure. With r-coniceine obtained by distillation in vacuum the
color réaction is very weak, and with Y-coniceine distilled in a current
of steam the reaction is not given at all.
As the benzoyl-4-amino butyl propyl ketone is at the same time
a ketone and a monoalkyl acid amide it is capable of reacting
with a great many substances. It reacts with alkyl magnesium
halides, aldehydes, phosphorus pentachloride and esters. With amyl
formate in presence of sodium ethylate the ketone combines with
elimination of amyl alcohol to an oxymethylene compound:
CH2 CH2
/N /N
H2O/ NCH2.0O.C3H7 H2O/ NC.('O.C3H7
+C.Hu(H.com) = | | + (5 H11.OH
HC2N H2CN CH.OH
N N
NH.CO.C6H5 NH.CO.C6H5
When this oxymethylene compound is distilled water is eliminated
and N-benzoyl B-butyryl tetrahydropyridine is formed:
CH2 CH2
/ N / N
H2C/ N.C.C.O.C3H7 H.C. N.C.C.O.(8 Hz
- | | + H2O
H2ON CH.OH H2CN / CH
N N /
NH.C6H5.00 N.C.O.C6H5
32
which upon boiling with acids seems to break up into tetrahydro-
pyridine, benzoic acid and butyric acid:
CH2 CH2
/N /N
H20 / 'NC.C.O.C3H7 H2C/ NCH
– | + C6H5.0O2H + C3H7.0O2H
H2ON / CH H2CN / CH
N / N /
N.C6H5.00 NH
If this interpretation of the reaction be correct the reaction
would present a remarkable case of a side chain being easily split
off from a partially reduced pyridine ring.
The addition product of Y-coniceine and benzaldehyde was pre-
pared by digesting molecular quantities of these substances till the
odor of both the aldehyde and the base disappeared. The addition
compound is soluble in acids with a yellowish-red color which soon
changes to green. When heated to boiling the acid solution is
colored green and an odor of benzaldehyde is developed. The addi-
tion product forms an amorphous platinum salt and a resinous gold
salt.
On treating r-coniceine hydrochloride with sodium nitrite nitrogen
is evolved and a colorless oily liquid of an agreeable odor is formed
which is volatile with steam. The substance seems to have the
formula, CsPI140, and to be either a ketone or an oxide.
CH2
/N
CH2 H2O/ NCH
/N |
CH/ NCH2 |
| H2ON / C.C3H7
t | N /
H2O CO.C3H7 O
Ketone. Oxide.
The fact that the compound does not form a semicarbazone
would seem to speak against the ketone formula. The compound is
probably identical with the substance of the same formula previ-
ously obtained by Hofmann in the exhaustive methylation of Y-coni-
ceine, and the successive steps of the methylation reaction can be
represented as follows: g
33
CH2 CH2
/ N /N
H2C/ NCH H2(!/ NCH2
| | — )
H2CN /C.C3H7 H2ON CO.C3H7
N / N
NH N(CH3)3]
Y-Comiceine.
CH2
/ N
CH2 H2O/ NCH
/ N. | l
HC/ N CH2 OI’ | |
| | H2CN / C.C3H7
| | N /
H2C CO.C3H7 O
From a consideration of the behaviour of a large number of
compounds the authors draw the conclusion that when a carbon
atom linked to nitrogen is also linked by two or three bindings to
another carbon atom and the nitrogen is also linked to a methyl
group, a nitroso group or a benzoyl group the compound easily
takes up one molecule of water and the linking between the nitrogen
and the carbon atom is destroyed. With the disappearance of the
multiple binding between the carbon atoms next to the nitrogen
atom the linking between the nitrogen and the carbon atom becomes
stable. Thus neurine H.O. (CH3)3N.CH=CH2, easily takes up one
molecule of water and trimethyl amine is formed whereas compounds
having the grouping, = N.CH2.00.0H8, for example, are perfectly
stable. Ber. Dtsch. chem. Ges., 38, p. 3094.
K. Löffler finds that when the splitting off of water from con-
hydrine is effected by heating the base with fuming hydrochloric
acid the product is a mixture of a-coniceine and 3-coniceine, but if
the splitting off of water is carried out by heating the base with
phosphorus pentoxide only 3-coniceine but no a-coniceine is formed
(comp. Hofmann, Ber. Dtsch. chem. Ges., 18, 9 and 105; Wertheim,
Ann. d. Chem., 100, 75). It would seem that when hydrochloric
acid is used one of the hydrogen atoms of the water comes from the
NH group with the formation of the liquid, tertiary, saturated
a-coniceine, but when phosphoric anhydride is used the NH group is
not affected and the product is chiefly solid, secondary, unsaturated
3-coniceine. In both cases the 3-coniceine is accompanied by a small
34
amount of a liquid secondary base which could not be obtained in
pure condition.
The 3-coniceine was prepared by heating conbydrine with phos-
phoric anhydride in closed vessels filled with hydrogen to 180–190°,
dissolving the reaction product in ice water and after making it
alkaline shaking it out with ether. The base was purified by fractional
distillation. 3-coniceine is volatile, has a coniine-like odor, melts at
40—41° and boils at 168.5°. It is less soluble in hot than in cold
water and is laevorotatory. It forms a nitrosamine and immediately
reduces potassium permanganate. It forms a crystalline hydro-
chloride, a chloraurate and an oily picrate. A double salt with
cadmium iodide was also obtained in oily condition.
If the heating of connydrine with phosphoric anhydride is carried
to a higher temperature (220°) the product is made up wholly of
liquid base. Ber. Dtsch. chem. Ges., 38, p. 3326.
Conhydrine.
M. Scholtz and P. Pawlicki find that the quaternary alkyl halides
of conly drine exist in two isomeric modifications whenever the five
radicles attached to the nitrogen atom are different from each other.
The only other alkaloid that was found to behave in this way was
coniine. (Comp. Ber. Dtsch. chem. Ges., 37, p. 3627; 38, p. 595.)
As in the case of coniine the isomers of conby drine differ from
each other in melting point, optical rotation, solubility and physio-
logical effect, but the double salts and the picrates of the isomeric
conby drinium derivatives are identical showing that in the formation
of these salts a transformation takes place. Some of the isomers of
the lower melting point are convertible into those of the higher
melting point by melting the former, but the reverse conversion can-
not be effected.
The authors have also tested the behaviour of N-ethyl tetra-
hydroquinaldine towards alkyl halides but no isomeric compounds
could be obtained.
The combinations prepared in this work were as follows: N-ethyl
conly drine + benzyl iodide, N-propyl conbydrine + benzyl iodide,
N-isoamyl conby drine + benzyl iodide, N-ethyl conby drine + ethyl
iodide and N-ethyl tetrahydroquinaldine + benzyl iodide. Only the
first three of these combinations could be obtained in two isomeric
modifications.
35
The tertiary N-alkyl derivatives used for the preparation of these
quaternary bases were prepared by the action of the alkyl iodides
upon the secondary bases in presence of either potassium hydroxide
or potassium carbonate. Ber. Dtsch. chem. Ges., 38, p. 1289.
Coniine.
C. Reichard has devised the following two color reactions by means
of which it is possible to distinguish between coniine and nicotine.
1. A spot of palladium chloride is prepared by evaporating a
few drops of its solution on a porcelain plate. A drop of the alkaloid
is put upon this spot and then a trace of hydrochloric acid added.
With coniine white fumes appear upon the mere approach of the acid
and the liquid soon solidifies to a mass of crystals with a light
green rim, whereas with nicotine there is no change whatever for
several hours.
2. On adding a drop of conine to a little powdered anhydrous
copper sulphate the mass assumes a dark blue color and the liquid
alkaloid is completely absorbed leaving the powder dry. Nicotine
does not color the copper sulphate and the powder remains moist
even after 24 hours. The same coniine reaction can be obtained with
crystalline copper sulphate but the reaction is slower in this case.
Concentrated sulphuric acid destroys the blue color.
Pharm. Centr.-H., 46, p. 252.
To distinguish between nicotine and coniine C. Reichard proposes
the following color reactions. A drop of the alkaloid is added to a
little powdered copper oxychloride (Cu2Cl2O) placed upon a porcelain
dish. Neither alkaloid is changed at first but upon addition of
hydrochloric acid a magnificent violet-blue color is developed with
nicotine and the color is stable for a long time, whereas coniine gives
a light green color which disappears completely after a while. In
the dry spot obtained from the coniine reaction shining needle-like
crystals can be noticed. The copper oxychloride used in this reaction
is prepared by reducing cupric chloride to cuprous chloride by means
of sulphurous acid or stannous chloride and then heating the cup-
rous chloride with water till it assumes a light green color.
On adding a drop of the alkaloid to the dried residue obtained
by drying out a drop of a solution of mercurous nitrate a black
color is immediately developed with coniine; nicotine is not affected
36
at first but the black color is developed on standing. Hydrochloric
acid does not change this black color.
If mercuric chloride be used in the last reaction a slight yellow
color is developed with both alkaloids. If some strong sulphuric
acid is then added a reddish color is developed with nicotine but the
coniine residue remains unchanged.
On adding a trace of the alkaloids to the residue obtained by
evaporating a solution of cobalt nitrate a violet color is developed
with coniine and a violet blue color with nicotine.
With a-nitroso-8-naphthol conine gives a dark green color,
whereas nicotine gives a yellowish-brown color. The nicotine residue
in this reaction is easily soluble in water but the coniine residue is
difficultly soluble even in hot water.
On adding a drop of the alkaloids to some 3-naphthol there is
no change at first but on now adding hydrochloric acid coniine re-
mains colorless whereas nicotine becomes yellow.
With bismuth submitrate neither of the alkaloids give any color
at first, but the addition of hydrochloric acid develops a yellow
color with nicotine and the color becomes more intense on standing.
Coniine under these conditions remains unchanged.
On adding to a drop of formalin a drop of nicotine, coniine or
sparteine a yellow color is developed only with nicotine, the other
two alkaloids remain unchanged. On now adding concentrated sul-
phuric acid coniine and sparteine remain unaffected but the yellow
color obtained from nicotine changes to that of a solution of cobalt
nitrate.
On adding to a few crystals of ammonium persulphate a drop
of nicotine, coniine or sparteine and then some sulphuric acid a
yellow color is developed with nicotine; coniine and sparteine remain
unchanged. Pharm. Centr.-H. , 46, p. 309.
M. Scholtz continues his investigations on the isomerism of the
quaternary coninium iodides (comp. Ber. Dtsch. chem. Ges.,
p. 3627). In previous articles it was shown that when alkyl halides
are added to N-alkyl coniine there are always formed two isomers
differing from each other in melting points, solubilities etc., whenever
the five radicles attached to the nitrogen atom are different from
each other. The coniine used for that work had been purified by
passing it through its hydrochloride. In the present work it is
shown that the same results are obtained with a coniine liberated
37
from the bitartrate. It is also shown that the isomerism of these
compounds cannot be due to the presence of isoconiine which accord-
ing to Ladenburg accompanies d-coniine in the plant and cannot be
separated from it, because if this were so we ought to get isomeric
N-alkyl coniines before the addition of alkyl halides. Besides, we
ought to get isomeric compounds even when two of the five radicles
attached to the nitrogen are the same.
The fact that these isomers can be repeatedly recrystallized with-
out becoming racemic would seem to indicate that the cause of this
isomerism is not the optical isomerism of the pentavalent nitrogen
because isomers of this kind are generally easily converted into
racemic compounds. We must assume that either the asymmetry of
the carbon atom gives greater stability to the nitrogen com-
plex or the isomerism of the quaternary coniine compounds is of
that particular kind which was found by Wedekind to exist in
certain other cases (Ber. Dtsch. chem. Ges., 32, p. 518; 37, p. 3894).
When the a-modification of ethyl benzyl coninium iodide is heated
to 180—185° it is almost completely converted into the 8-modifi-
cation, but the 8-modification when heated above its melting point
is decomposed without even partly becoming converted into the
a-variety. The a- and 8-varieties differ from each other also in
physiological activity. While both are more poisonous than coniine
or N-ethyl coniine the a-compounds, with the exception of the iso-
amyl derivatives, are more poisonous than the 8-compounds.
The following new addition products were obtained in this work.
a- and 3-ethyl allyl coninium iodide were prepared by the action of
allyl iodide upon ethyl coniine and separated from each other by
fractional precipitation with ether from alcoholic solution. The
a-compound melts at 175°, the 8-compound melts at 191°.
An attempt to prepare the iodoethylate of N-allyl coniine was
not successful because on warming coniine with allyl iodide and
potassium hydroxide, the allyl iodide is partly decomposed while
another part forms N-diallyl coninium iodide, C8H16N(C3H5)21.
N-n-propyl coniine was obtained together with a small amount
of dipropyl coninium iodide, C8H16N(8 HT)2 I, by boiling coniine with
n-propyl iodide and potassium hydroxide. On treating the n-propyl
coniine with benzyl iodide N-n-propyl benzyl coninium iodide is ob-
tained in two modifications, a and 3. They were separated from
38
each other by means of water or acetone in which the a-compound
is more soluble than the 3-compound.
N-n-butyl coniine was obtained by the same method as the
n-propyl compound and then converted into a- and 3-N-n-butyl
benzyl coninium iodide by means of benzyl iodide. The isomers were
separated from each other by boiling with a little acetone which
takes up only the a-compound.
Ber. Dtsch. chem. Ges., 38, p. 595.
Corydaline.
The constitution of corydaline and some of its oxidation pro-
ducts were investigated by O. Haars. Previous investigations by
other chemists have established a close relationship between cory-
daline and canadine. Canadine which is colorless is oxidizable by
iodine to berberine which is yellow.
C21H21NO4 + 4I = (21H18NO4.I -- 3HI
Canadine. Berberine IO dide.
In the same way colorless corydaline is oxidizable by iodine to
yellow dehydrocorydaline.
C22H27NO.4 + 4I = C22H24NO4 + 3HI
Corydaline. - Dehydrocorydaline.
The formation of certain oxidation products from corydaline ob-
tained by Dobbie and Lauder has led these chemists to propose for
corydaline the following formula
O.CFIs
N
/ N.O.UHs
CH3.O CH2
| |
choſ's y^2^2 /
|NH
|N
N / N /N /CH2
/ N / N/
CH CH2
th.
Cory duline.
(I)
According to Dobbie and Lauder both ortho and metahemipinic
acids are to be found among the oxidation products of corydaline,
39
but according to Ziegenbein and Martindale only the ortho acid is
formed in this oxidation.
(H3.O
/N /N
CH3O/ N–CO2H chor Sºon
|
| | |
N /–CO2H CH3. ON /—CO2H
N / N /
Orthohemipinic Acid. Metahemipinic Acid.
(II) (III)
If both of these acids are formed from corydaline the formula of
this alkaloid ought to be as given (I), but if only the Ortho acid is
formed then the formula of corydaline must be as follows:
O.CH3
Z N
cº-o/ N
CH3.O CH2
|
CEL3
- (IV)
The author proves the correctness of the statement of Dobbie
and Lauder about the formation of both hemipinic acids from cory-
daline. Hence formula (I) for this base is the correct one.
According to Dobbie and Marsden dehydrocorydaline has the
formula, C22H2SNO.4 and the following constitution :
O.CH3
/ N
% NO.CH3
chº 9 . |
º NZ Nº Nº.
| | |N
N/\!/ ^, /CH2
C CH2
40
The authors find that the formula of dehydrocorydaline is
C22H5NOs and that it is a quaternary ammonium base which under
certain conditions changes to a pseudo-base having either a ketone
or a carbinol form.
O.CH3
O.C.H.8 N
/ > / NO.CH3
/ NO.CH3 | |
CH (SH CH3. O CH 2 |
3.0) J N / /
/* ^ ^ / (H3. O/ N/ N/ N/
º | NH
|N /N 'N /CH2
N / N /N /CH2 N/ N N /
\/ N/ N / N CH2
C OH CH2 º-o
th. CH3
Dehydrocorydaline. (Ammonium Base.) Dehydrocorydaline (Retone Formula).
(VI) (VII)
O.CH3
ºpen.
chº 9i y |
cº-o/ Y N / Nº
| N
/N / N /CH2
N / Y `i.
/ N
/ N
CH3 OH
Dehydrocorydaline (Carbinol Formula).
(VIII)
The preparation of corydaline was carried out by the method of
J. Gadamer (Arch. d. Pharm., 240, p. 21). By this method a larger
yield of alkaloid is obtained than by the methods used by other in-
vestigators. The free dehydrocorydaline is very difficult to isolate
because even traces of moisture quickly decompose it and in presence
of carbon dioxide it changes to a carbonate.
The author has succeeded in preparing free dehydrocorydaline by
the following method. Dehydrocorydaline iodide was converted into
the sulphate by means of silver sulphate, the sulphate decomposed
41
by strong potassium hydroxide (50%) and the free base shaken out
with absolute ether. The ether was quickly separated from the
aqueous liquid and, after drying it with solid alkali and concentrat-
ing in vacuum, put aside in a cold place to crystallize.
The ketone nature of dehydrocorydaline (W II) was shown by
converting it into an oxime by means of free hydroxylamine in
ethereal solution and by condensing it with para-amido dimethyl
aniline.
According to J. Gadamer and H. Wagner (Arch. d. Pharm., 240,
p. 37) when dehydrocorydaline is reduced two bases are formed which
are isomeric with corydaline but are optically inactive. One of these
bases melts at 135°, the other at 158—159°.
Attempts to split up these inactive bases into active components
gave following results. The lower melting base could not be split up
either by means of ammonium bromcamphor sulphonate, or by
means of quinic acid or by using tetraacetyl quinic acid. The base
melting at 158–159° could only be partly split up into a d- and a
l-modification. As both modifications differed in crystalline form
from corydaline and had a much lower specific rotation than cory-
daline the base melting at 158–159° cannot be regarded as the
racemic form of the natural base. The two asymmetric carbon
atoms of corydaline being of unequal optical activity and the alka
loid being dextrorotatory we must assume that either both carbon
atoms have a d-function or that one has a d-function greater than the
Other which has an l-function. In the first case an 1-corydaline would
have two asymmetric carbon atoms both of which have an l-function
and an inactive corydaline would, like racemic tartaric acid, be made
up of one molecule d- and one molecule 1-corydaline. Such a racemic
corydaline Ought to be easily decomposable into its d- and l-com-
ponents. In the second case the inactivity of an isomeric corydaline
can be explained by assuming that the functions of the asymmetric
carbon atoms in one molecule are just the reverse of the functions
of these atoms in another molecule. As in this case the functions of
the asymmetric atoms in each molecule work in opposite directions
it would be difficult to split up such an inactive corydaline into a
d- and an 1-modification. Owing to the fact that the base of the
melting point 158–159° is difficultly split up into active components
it was named r-mesocorydaline and the d- and l-bases obtained from
it having a lower rotation than natural cory daline were named d_
42
and l-mesocorydaline. The base melting at 135° would therefore
seem to be r-corydaline though as said before the author has not
succeeded in splitting it up into d- and l-components.
Another oxidation product of corydaline is corydinic acid,
C18H17NO6, obtained by oxidizing the alkaloid with dilute nitric
acid. The acid crystallizes from hot water in two forms: in color-
less rhombohedrons containing one molecule of water of crystalli-
zation and in opaque needles containing two molecules of water of
crystallization. Dobbie & Marsden assigned to the acid the following
constitutional formula : if - -
O.C.H.8
/ º
|
º / \ º
|N
HO2CTN /N / CH2
N/
N/
C
th.
CH2
The author shows that the acid is monobasic and is a quaternary
base, hence its constitution must be as follows:
*.
QCh.
º NO.CH3
CH i -
HO2C_z ~~~~
# | |
N |
0.00-s /'N /
N/TS/
CH 8.0 CH2
Corydinic acid.
(IX)
The quaternary nature of corydinic acid was shown by beating
it with the theoretical amount of methyl iodide and potassium
hydroxide to 80–90°. Under these conditions the iodide (not the
iodomethylate) of the dimethyl ester of corydinic acid is formed:
43
O.CH3
/*
Ž NO.CH3
| i
CH | |
/s, /*s /
CH3.O2C_/ N/ /
| |
! | |
CH3.O2CTN / N /CH2
N / | N/
CH3.0 | (H2
Iodide of dimethyl corydinate.
(X)
By means of silver chloride the iodide was converted into the
corresponding chloride. The chloride cannot be dried at 100° with-
out decomposition. It contains four molecules of water of crystalliza-
tion which it loses in vacuum over sulphuric acid. As it is a salt of
a quaternary base the decomposition at 100° must be accounted
for by supposing that methyl chloride is split off. From the chloride
a chloraurate and a chloroplatinate were obtained.
By substituting ethyl iodide for methyl iodide in the above re-
action the iodide of the diethyl ester of corydinic acid was prepared.
The iodide of the ethyl ester is saponified by simple recrystallization
from alcohol.
On boiling corydinic acid with hydriodic acid the two methoxy
groups are replaced by two OH groups.
The new phenolic acid when titrated with alkali behaves like a
dibasic acid. As corydinic acid (IX) is a monobasic acid it must be
assumed that in the phenol the linking between the nitrogen atom
and the carboxyl group is opened, that a hydrogen atom of one of
the OH groups goes to the carboxyl group and that the oxygen
atom of this OH group forms the betaine binding between nitrogen
and carbon.
By reducing corydinic acid we ought to get a colorless substance
containing an asymmetric carbon atom (comp. Arch. d. Pharm.,
1905, 57) and therefore decomposable into active components. The
alithor Succeeded in reducing the acid by means of zinc and sulphuric
acid to a colorless substance but the yield was too small for further
investigation.
Among the oxidation products of corydaline Dobbie and Marsden
44
obtained oxalic acid and methyl pyridine tricarboxylic acid. The
author succeeded in proving the formation of oxalic acid but no
pyridine acid could be found when nitric acid was used as oxidizing
agent.
On oxidizing corydaline with potassium permanganate Dobbie
and Marsden obtained corydilic acid to which they ascribe following
constitution :
O.CH3
ZN
/ NO.CH3
C |
/ /N /
HO2C_2^ N/ N/
| |
| (XO.OH
/N II
HO2CTN
N /
()
(Ha
The author shows that the acid is a tertiary not a secondary
base and assigns to it following constitution :
O ( II;
/ º
º
º (O2 II
CfI3
Corydilic Acid.
(XI)
The tertiary nature of this tribasic acid was shown by the com-
pound taking up four methyl groups when treated with methyl iodide
and potassium hydroxide giving the iodomethylate of trimethyl
ester of corydilic acid.
While the author has not succeeded in isolating from these oxida-
tion products metahemipinic acid and methylpyridine tricarboxylic
acid in sufficient quantities it was nevertheless possible to prove the
45
presence of the pyridine acid by several reactions and of metahemi-
pinic acid by its crystalline form and varying melting point.
Another result obtained by Dobbie and Lauder and verified by
the author is the formation of corydaldine in the oxidation of cory-
daline with cold potassium permanganate
O CH3
/ ,
(SO2H / T.CH3
/
Hoc / NZ | |
/ N
Hoc o, 2 N/
HO2CT N | |
N |
C HNN /CH2
| N /
CH3 CH2
Methylpyridine Tricarboxylic Acid. Corydaldine.
(XII) (XIII)
With nitrous acid corydaldine forms a nitrosamine which is con-
verted by warm sodium hydroxide into a sodium salt with the
elimination of nitrogen. Acids convert this sodium salt into a
lactone which upon oxidation gives metahemipinic acid (III).
CH3. O CO.ONa) CH3.O ‘CO ... O
\ch. 2^ Yeº |
CHs.o/” NCH2—CH2.OH CHs.o/*NCH, CH,
Sodium Salt. Lactone.
Arch. d. Pharm., 243, p. 165.
O. Haars has investigated the alkaloids of Corydalis cava and
Corydalis solida. Besides amorphous bases these drugs were found
to contain chiefly bulbocapnine, C19H19NO4, together with small
amounts of two new alkaloids. The formula of one of these alka-
loids is, C21H21NO3, of the other, C21H23NO7 or C21 H25NO7.
The first of these two alkaloids was separated from the other alka-
loids of the drug by means of alcohol in which it is insoluble. Con-
trary to the other Corydalis alkaloids this alkaloid is laevorotatory.
It contains neither an OH nor a CH3O group. The other of these
two alkaloids was isolated by means of potassium sulphocyanate
and separated from bulbocapnine by shaking out their ethereal
solution with an insufficient amount of hydrochloric acid. Under
these conditions only bulbocapnine is extracted from the ethereal
liquid. On then shaking out the latter with more acid the other
46
alkaloid is taken out. This alkaloid contains one CH3N and two
CH3O groups and shows the phenomenon of triboluminescence.
No tropine could be found in the drugs.
Arch. d. Pharm., 243, p. 154.
Cotarnine.
According to Wilh. Ahlers acetylhydrocotarnine acetic acid has
the following constitution assigned to it by C. Liebermann :
O.CH3
/ º
NO N/-CILCH.N(CH.) (CH3.OO)
CH2 /
N
That this is so was shown by the fact that the compound is
capable of taking up two atoms of bromine, or two atoms of
hydrogen and that by oxidation with potassium permanganate it is
converted into acetylhydrocotarnine which can also be prepared
from cotarnine and acetic anhydride. When the acetylhydrocotarnine
is treated with acetic anhydride in presence of sodium acetate it is
reconverted into acetylhydrocotarnine acetic acid. The analogous
benzoylhydrocotarnine acetic acid can be prepared from benzoyl-
hydrocotarnine and acetic anhydride in presence of sodium acetate.
The compound previously obtained by Bowman by boiling acetyl-
hydrocotarnine acetic acid with hydrocotarnine acetic acid is the
hydrochloride of the hydrocotarmine acetic acid. This was shown by
converting the methyl ester prepared from this salt into the iodo-
methylate of the methyl ester of hydrocotarnine acetic acid.
Hydrocotarnine acetic acid,
2CHCH.Cosh
NCH2CH2.NH.CHA
was prepared by treating the above hydrochloride with silver oxide,
removing excess of silver by Sulphuretted hodrogen and concentrat-
ing to crystallization.
Hydrocotarnine methyl acetate,
2CII:CH.CO2CHA
chaos.cºhochºn CH2.N.H.CH
2. 2.T * $3
was prepared by passing a current of hydrochloric acid gas into a
solution of hydrocotarnine acetic acid in methyl alcohol. After
CH2O2:06H(CH3O)
47
distilling off the alcohol and diluting with water the liquid was made
alkaline and shaken out with ether. The ester is oily at first but
becomes solid in the cold and can be recrystallized from methyl
alcohol. The ester forms a platinum salt which is decomposed at
about 90° without melting. By the action of methyl iodide the ester
was converted into the iodomethylate of the methyl ester of methyl-
hydrocotarnine acetic acid,
2CHCH.co, CH,
chorench-oº: CH2.N(CH3)3 I
2. 2. ' 3) 3
which was separated from the hydriodide formed in the reaction by
means of water in which the hydriodide is Imore soluble than the
iodomethylate.
The dibromide of acetylhydrocotarnine acetic acid,
2CHBr CHBr cosh
CH2O2:06H(CH3O)
NCH2CH2.N(CH2)(CH3CO)
was prepared by adding bromine dissolved in glacial acetic acid to
a solution of acetylhydrocotarnine acetic acid in the same solvent.
The dibromide is soluble in sodium carbonate and is reprecipitated
by acids. The dibromide was converted into the corresponding ester
by passing hydrochloric acid into its solution in methyl alcohol.
Dihydroacetylhydrocotarnine acetic acid,
2CH2CH2.(CO2H)
CH2.O2:06H(CH3O)
* NCH2CH2.N(CH2)(CH.CO)
was made by treating an alkaline solution of acetylhydrocotarnine
acetic acid with sodium amalgam and precipitating the dihydro
compound by the addition of acid. Unlike the original compound
it does not reduce permanganate immediately.
Acetylcotarnine,
/CHO
CH2O2:06 H (CH3O)
NCH2CH2.N(CH2)(CH3CO)
was prepared from acetylhydrocotarnine acetic acid by dissolving
the acid in sodium carbonate and adding potassium permanganate
to the solution. After filtering off from the manganese dioxide the
acidulated liquid was concentrated to small bulk when the acetyl-
cotarnine separated out on cooling.
48
The same acetylcotarnine can be prepared by treating cotarnine
with acetic ahydride and separating the acetyl compound from un-
changed cotarnine and acetylcotarnine acetic acid formed in the
reaction by means of sodium carbonate in which the latter two are
soluble.
On warming acetylcotarnine in alcoholic solution with hydroxyl-
amine hydrochloride an oxime was prepared which was soluble in
alkalies but insoluble in acids.
On heating acetylhydrocotarnine with acetic anhydride and
sodium acetate to 100–120° it is converted into acetylhydro-
cotarnine acetic acid. It was identified by its ethyl ester and silver
salt.
Benzoylhydrocotarnine acetic acid,
H2O2:06 H (CH3O /CHCH.CO2H
CH2O2:06 H (CH3O)
NCH2CH2NCH5)(CH3CO)
was prepared from benzoylcotarnine and acetic anhydride in the
same way as the corresponding acetyl compound. By treating the
silver salt of this acid with ethyl iodide the corresponding ethyl ester
was prepared. Ber. Dtsch. chem. Ges. 38, p. 2873.
Ephedrine.
E. Schmidt has succeeded in preparing synthetically a compound
which is isomeric with methyl ephedrine methyl chloride and differs
from the corresponding derivative of the natural base only in that
the synthetic compound is optically inactive. It has not yet been
established whether the synthetic compound is decomposable into
active components.
It was shown by E. R. Miller (Arch. d. Pharm. 240, p. 481) that
when methyl ephedrine methyl hydroxide obtained by exhaustive
methylation of ephedrine is heated it breaks up according the follow-
ing equation: †
CoEI10(OH).N(CH3)3.OH = CoHo. OH + (CH3)3 N + H2O
As the compound CoHo. OH was easily oxidable by cold chromic
acid mixture to benzoic acid or benzoic aldehyde it was supposed to
contain the group
2- /
C6H5.0N OH Or Co H 5.0 H.OH
from which the conclusion was drawn that methyl ephedrine methyl
49
hydroxide had the constitution, C6H5.0H(OH).0H2.0H2.N(CH3)3.OH.
A compound of this constitution was prepared by combining styryl
chloride, C6H5.0EI:CH.CH2Cl, with trimethylamine, converting the
product into a dibromide, changing the dibromide to the correspond-
ing bromhydrine and reducing the bromhydrine with nascent
hydrogen:
C6H5.0H:CH.CH2.0l-H (CH3)3N = C6H5.0H:CH.CH2.N(CH3)3.01–.
— CoEI5.0H.Br.CHBr.CH2N(CH3)3.0l — C6H5.0H(OH). CHBr.CH2.
N(CH3)3.01 — C6H5.0H(OH).0H2.0H2.N(CH3)3.OH.
The styryl chloride was prepared by the action of hydrochloric
acid upon cinnamic alcohol. On digesting the styryl chloride with
a solution (33%) of trimethylamine in absolute alcohol and eva-
porating the solvent the addition product of styryl chloride and tri-
methylamine was left as a syrupy liquid which was identified by
means of the chloraurate and chloroplatinate.
The dibromide was prepared by adding an alcoholic solution of
bromine to an alcoholic solution of the styryl chloride — trimethyl-
amine and evaporating the solvent.
On boiling the dibromide with water one of the bromine atoms
is replaced by an OH group giving the bromhydrine C6H5.0H(OH).-
CHBr, CH2.N(CH3)3.0l.
The position of the OH group in this compound was shown by
its similarity in constitution with the bromhydrine obtained from
dibromcinnamic acid. As the latter is reducible by nascent hydrogen
to 3-phenyl lactic acid, C6H5.0H(OH). CH2.0O2H, the OH group in
the styryl chloride-trimethylamine must occupy the same position
as the OH group in the bromhydrine of cinnamic acid.
The identification of the brom hydrine was carried out by means
of the chloroplatinate.
On reducing the bromhydrine with zinc and sulphuric acid an
oily liquid was obtained which had the same odor as the alcohol,
CoHo. OH obtained from methyl ephedrine methyl hydroxide. On
comparing the chloraurate made from the reduction product of the
bromhydrine with the chloraurate of methyl ephedrine methyl chloride
they were found to be identical in every respect.
Arch. d. Pharm., 1905, 73.
50
Harmine.
O. Fischer and Chr. Buck continue their investigations on harmine
and harmaline. Previous investigations have shown that these
alkaloids are made up of a benzol nucleus combined with
another nucleus which contains the two nitrogen atoms
and that harminic acid obtained by oxidation of harmine
or harmaline when heated to 345° loses both carboxyl groups and
is converted into apoharmine, C8H8N2. The authors find that when
heated with hydrochloric acid to 190—200°, harminic acid loses only
one carboxyl group and is converted into the hydrochloride of apo-
harmine carboxylic acid Cs HTN2(CO2H).HCl. The hydrochloride can
be recrystallized from hot moderately strong hydrochloric acid. From
the hydrochloride the free apoharmine carboxylic acid can be ob-
tained by adding excess of sodium acetate to a hot solution of the
hydrochloride. The apoharmine carboxylic acid has a neutral reac-
tion and is not fluorescent. It is soluble in dilute alkalies, ammonia
and dilute sulphuric acid but is insoluble in most organic solvents.
Carbon dioxide precipitates it from solution in alkalies. It forms a
chloraurate and a chloroplatimate both of which are easily dissociated
by water. On heating the acid to 330° it loses carbon dioxide and
is converted into apoharmine. The acid is not reducible by sodium
in amyl alcoholic solution and is not affected by hydriodic acid of
the specific gravity 1.75 at 165°. With stronger hydriodic acid
(sp. grav. 2.00) it breaks up at 2008 to apoharmine and some of
its reduction products. The chief difference between apoharmine
carboxylic acid and harminic acid consists in the greater basicity
and greater solubility in water of apoharmine carboxylic acid.
Methyl apoharmine carboxylic acid in the form of its hydriodide
was obtained by heating apoharmine carboxylic acid with methyl
iodide in methyl alcoholic solution to 100°. The free methyl apo-
harmine carboxylic acid, Cs H6(CH3)N2(CO2H) was obtained from
the hydriodide by neutralizing the concentrated solution of the
hydriodide with ammonia. The same methyl apoharmine carboxylie
acid can be obtained by heating methyl harminic acid with strong
hydrochloric acid to 190° and neutralizing the hydrochloride thus
obtained with ammonia. The ammonium salt of methyl apoharmine
carboxylic acid has a blue fluorescence (difference from the non-
methylated acid).
Nitro apoharmine carboxylic acid, C6H6(NO2)N2(CO2H) was pre-
51
pared by boiling apoharmine carboxylic acid with strong nitric acid
(1.5) for about 10 hours. The nitro compound is soluble in water
but insoluble in most organic solvents. It has no definite melting
point commencing to darken at 190° and turning black at 250 to
270°. The same nitro compound can be obtained by boiling har-
minic acid with concentrated nitric acid.
Nitro apoharmine, C8H1(NO2)N2, prepared by a previously des-
cribed method (Ber. Dtsch. chem. Ges., 1897, p. 2488), has both acid
and basic properties. Owing to the solubility of the nitro compound
in alkalies it was thought that the nitro group was linked to nitro-
gen as in nitramines, but further investigation showed this view to
be incorrect. The solubility of nitro apoharmine in alkalies is
possibly due to the same cause as the solubility in alkalies of the
nitrobenzimidoazoles.
The nitro apoharmine forms a nitrate which crystallizes with
half a molecule of water of crystallization.
Methyl nitro apoharmine, C8H8(CH3)(NO2) N2, was prepared by
heating nitro apoharmine with methyl iodide in methyl alcoholic
solution to 100° and adding ammonia to the hydriodide thus ob-
tained. The nitro base forms a golden yellow chloraurate and a
yellowish-red chloroplatinate. The methyl nitro apoharmine con-
tains a tertiary nitrogen atom as it forms an ammonium iodide
base, C8H8(CH3)2(NO2)N2.I, when treated with methyl iodide.
Nitro apoharmine is not affected by chromic acid. By reduction
with tin and hydrochloric acid it is converted into an unstable
amido apoharmine, Cs H1(NH2)N2. When oxidized with hot ferric
chloride the amido apoharmine evolves an odor resembling quinone.
Dihydroapoharmine, Cs H10N2, prepared by a previously described
method (Ber. Dtsch. chem. Ges., 1889, p. 741) forms a crystalline
picrate which is suitable for the purification of the reduced base. A
molecular weight estimation of the dihydro base corroborated the
previously established formula. Chromic acid reconverts dihydro-
apoharmine into apoharmine.
The secondary nature of harmine could be shown only by
methyation. Attempts to make acyl derivatives or a nitrosamine
were not successful. On trying to acetylize it by means of acetic
anhydride in presence of sulphuric acid (Thiele's method) harmine
sulphonic acid, C18H11N2O.(SO2.OH) was obtained. The sulphonic
acid is difficultly soluble in water and contains the SO3H group
52
linked to nitrogen which was shown by the fact that boiling hydro-
chloric acid decomposed the sulphonic acid into SO2 and harmine
hydrochloride.
On heating harmine sulphonic acid with hydrochloric acid to
150°, sulphur dioxide and methyl chloride are split off leaving a
residue of harmol, C12H9(OH)2.
Ber. Dtsch. chem. Ges., 1905, 329.
Metanicotine.
E. Maas finds that when metanicotine is reduced by means of
sodium and absolute alcohol the base is converted into hexahydro-
metanicotine. The six hydrogen atoms seem all to go into the
pyridine nucleus.
CH-CH2 CH-CH2
| ch,
AN &H CH2.NH.CH3 H2C “ N CH-CH CH2.NH.CH3
| +6H = |
N / H2O N / CH2
K NH
Metanicotine. Ber. Dtsch. chem. Ges., 1905, 1831.
Mezcaline.
Attempts to establish the constitution of mezcaline were made
by A. Heffer and R. Capellmann. According to previous experiments
(Ber. Dtsch. chem. Ges. 1901, 3011) this alkaloid seems to have the
constitution of 3, 4, 5-trimethoxybenzylmethylamine,
/CH2NH.CH
chº
(O.CH3)3
Hence if trimethoxybenzylamine be converted into trimethoxybenzyl-
trimethyl ammonium iodide the product ought to be identical with
the iodomethylate of methyl mezcaline. But as this was found not
to be the case mezcaline cannot have above constitution.
An attempt to make the trimethoxybenzylamine by reducing
the nitrile of the trimethyl ether of gallic acid,
CN
C6H
*\(0.0Hs),
53
was not successful. Most of the nitrile was saponified in the reaction
and some hydrocyanic acid was also formed. The amine was then
successfully prepared by reducing the aldoxime of the trimethyl ether
of gallic aldehyde. The aldehyde was prepared by oxidation of the
corresponding alcohol. The same aldehyde was also obtained by
treating hexamethoxybenzil, (CH3O)3.06H2.00.00.06H2.(O.CH3)3,
with sodium carbonate and potassium cyanide in alcoholic solution.
Under these conditions the benzil derivative breaks up into the
trimethyl ether of gallic aldehyde and the trimethyl ether of gallic
acid. After separating the aldehyde from the acid by means of
sodium bisulphite it was converted into the Oxime by means of
hydroxylamine hydrochloride and sodium carbonate.
When the oxime is treated with dry hydrochloric acid in ethereal
solution a crystalline hydrochloride is formed but no isomeric Oxime
could be obtained.
The reduction of the Oxime to the amine was carried out by
adding sodium amalgam in small portions to a warm solution of
the oxime in alcohol, keeping the solution acid by frequent addition
of glacial acetic acid. The unattacked Oxime was separated from
the amine by shaking their aqueous acid solution with ether which
removes the oxime and then, after making the liquid alkaline, shaking
out again with ether which now extracts the amine.
The trimethoxybenzylamine was converted into trimethoxybenzyl
trimethyl ammonium iodide by means of methyl iodide in presence
of potassium hydroxide.
The trimethoxybenzyl trimethyl ammonium iodide, C6H2(O.-
CH3)3. CH2.N(CH3)31, melted at 2.18° and 11.76 parts of it dissolved
in 100 parts of water, hence it was not identical with the iodo-
methylate of methylmezcaline which melts at 225 and of which only
1.88 parts dissolve in 100 parts of water.
Ber. Dtsch. chem. Ges, 1905, 3634.
Morphine.
E. Wongerichten continues his investigations of morphenol, one
of the decomposition products of morphine. It is shown that
(3-methylmorphimethine from which the methyl ether of morphenol
is obtained must be aderivative of morphenol
/7TEN
/ N
/s – N —IN
/ \ ^ 2\
N5 / N /
N4 / N__3^
N
N /
N/
O
Morphenol.
The group —CH2.0H2.N(CH3)2 in 3-methylmorphimethine must
be linked either in 1 or 8.
By the action of bromine upon methyl morphenol brom methyl
morphenol is formed which has the same melting point and the
same crystalline form as the bromine derivative obtained by con-
verting brom morphine into brom methyl morphenol. These two
brommethyl morphenols are nevertheless not identical behaving in
an entirely different way towards oxidation and further bromination.
The brom methyl morphenol made from brom morphine and named
a-brommethyl morphenol is converted by further bromination into
a dibromsubstitution product whereas the brom methyl morphenol
obtained from methyl morphenol (named 8-brom methyl morphenol)
gives upon bromination a dibromaddition product which resembles
the bromaddition product of phenanthrene. Like the latter the
6-compound is not stable losing hydrobromic acid a little above
100° and changing into a dibromine derivative. Upon oxidation
with chronic acid the a-compound gives a crystalline quinone whereas
the 3-compound under the same conditions gives an amorphous
product.
In both the a- and 8-brom methyl morphenol the bromine atom
cannot be attached to either of the two “bridge” carbon atoms
because from both of them brominated Orthoquinones can be ob-
tained in which both of these carbon atoms must be present in the
form of CO groups. Ber. Dtsch. chem. Ges., 1905, 1851.
L. Knorr has tried to establish experimentally whether the
complex .C2H4...N(CH3)2 in methyl morphimethine is directly attached
to the phenanthrene nucleus or is linked to it by means of an oxygen
atom in the same way as the groups are linked to each other in
ethers. In order to explain the formation of oxethyldimethylamine,
HO.CH2.0H2.N(CH3)2, when methylmorphimethine is treated with
55
acetic adhydride, the hypothesis had been made that the .C2H4NOCH3)2
complex is attached to the phenanthrene ring by the aid of an “in-
different” oxygen atom. It followed from this supposition that
morphine contained an oxazine ring,
/ O——CH2
(HO)2C14H10 |
NN(CH3)2.éHe
and that methylmorphimethine had the following constitution

N. O.CH3
/ O.CH2.0H2.N(CH3)2
|
N/N
| H.
NZ
Methylmorphimethine.
OH
(I)
But experimental data which have accumulated during the last
few years seem to speak against this formula for methyl morphime-
thine and hence against the presence of an oxazine ring in morphine.
These data are as follows: When methyl morphimethine is heated
with sodium ethylate or the iodomethylates of codeine or thebaine
are heated with alcohol dimethyl-aminoethyl ether, C2H5 O.C2H4N-
(CH3)2, is formed. This would seem to indicate that the oxethyl
dimethylamine complex is not a primary decomposition product but
is formed from vinyl dimethylamine, (CH3)2N.CH = CH2, formed at
first in the reaction, and that this vinyl dimethylamine is then con-
verted into oxethyl dimethylamine by taking up one molecule of
alcohol. Furthermore, if the above formula for methyl morphime-
thine (I) were correct the compound as a dihydrophenanthrol Ought
to easily lose one molecule of water and change to the purely
aromatic methyl morphol ether of ethanol dimethylamine (II)
But all attempts to split off water from methyl morphimethine
were unsuccessful.
56

O.CH3 O.CH3
/ O.CH2.0H2.N(CH3)2 /N/ochschisch).
| | |
N º
N Vº
(II) (III)
By the action of chlorethyl-dimethylamine upon the sodium salts
of thebaol and methylmorphol the author prepared dimethylamino-
ethyl ether of thebaol (III) and dimethylaminoethyl ether of methyl-
morphol (II)
If methylmorphimethine had the formula given above (I) these
two ethers having constitutions similar to that of methylmorphime-
thine ought to behave towards certain reagents very much like
methylmorphimethine. But attempts to decompose these ethers by
means of hydrochloric acid or acetic anhydride showed that while
the reaction is of the same nature as in the case of methylmorphi-
methine it is nevertheless much slower. Again, these ethers are not
affected by sodium ethylate at 150° whilst methylmorphimethine is
decomposed by this reagent forming dimethylamino-ethyl ether
N(CH3)2.02H4.0.02H5. It was also found that thebainone (see next
paragraph) which does not contain an “indifferent” oxygen atom
also yields oxethyldimethylamine when treated with acetic anhydride.
From all these considerations it follows that methylmorphime-
thine cannot have the constitution given to it above (I) and that
morphine, codeine and thebaine do not contain an oxazine ring.
The indifferent oxygen atom in these alkaloids is therefore not in the
nitrogen containing side ring but in a furfurane ring attached to the
meso-position of the phenanthrene nucleus (the meso-position is the

…". S_2^*, 'Y
`… N ºf
10 1 1
57
linking at 4 and 5, the linking at I and 11 being called the peri-
position) in the same way as in methylmorphenol obtained from
B-methylmorphimethine

— `_
_T^_^
N_2 > *
\ ^
Methylmorphenol.
The formula of methylmorphimethine, C19H23NO3, can therefore
be resolved as follows:
—O.CH3 (in 3)
C14H15 >O (position 4 and 5)
5 times sub- —OH (in 6)
stituted —C2H4...N(CH3)2 (position not determined)
H4 (probably in benzol ring III)
and that of morphine as follows:
, —OH (in 3), phenolic
C14H4 º º O.
5 times sub- *-E (in ) alco O 11C
stituted —C2H4 side ring
—N.CHs position unknown
H5 added in rings II and III.
The exceptionally easy splitting off of the nitrogen containing side
ring, C2HAN.CH3, which takes place on simply boiling the iodo-
methylates of thebaine and codeinone (hence easier even than the
splitting off of carbon from chloral) and the displacement of the
substituted groups shows that, like the groups in certain quinoid
compounds (Ber. Dtsch. chem. Ges., 1904, 3503), the substituted
groups in the reduced phenanthrene ring possess an astonishing
mobility.
The following compounds were prepared in the course of this
investigation. Phenylether of oxethyldimethylamine, C6H5.O.CH2.-
N(CH3)2, was prepared by heating sodium phenolate with chlorethyl-
dimethylamine, Cl,CH2.0H2.N(CH3)2, in alcoholic solution and, after
58
removal of excess of alcohol and phenol by a current of steam,
setting the ether free by means of alkali. The ether forms a charac-
teristic chloraurate.
Methylmorphol ether of ethanol dimethylamine, (II) was made
by heating in an atmosphere of nitrogen an alcoholic solution of
chlorethyldimethylamine, methyl morphol and sodium. After
removing excess of alcohol by steam the unchanged methylmorphol
was removed by shºuking out the acidulated liquid with ether. The
methylmorphol ether of ethanoldimethylamine is an oily liquid and
forms a characteristic difficultly soluble hydrochloride, a picrate and
an iodomethylate. -
The thebaol ether of ethanol dimethylamine (III) was prepared
from thebaol by the same method as the methylmorphol ether from
methylmorphol. The thebaol ether is an oily liquid and forms a
picrate and an iodomethylate. The latter crystallizes with one and
a half molecules of alcohol of crystallization.
The decomposition of the methyl morphol ether of ethanol
dimethylamine (II) by means of gaseuos hydrochloric acid was
carried out in the same way as the decomposition of methylmor-
phimethine (Ber. Dtsch. chem. Ges., 1894, p. 1144; 1904, p. 3495).
The reaction is the same in both cases. The prodncts obtained from
the methylmorphol ether were morphol, tetramethylethylenedianline
and ethanoldimethylamine. As had been shown previously (loc.
cit.) the basic products of this reaction are formed by the action of
the alkali upon chlorethyl dimethylamine which is the primary
product. - ‘sº
On heating the methylmorphol ether (II) with acetic anhydride
the same decomposition takes place as when methylmorphimethine
is subjected to the same reaction. The products in the case of the
ether are ethanoldimethylamine and methylmorphol.
Unlike thebaine the theba.ol ether of ethanoldimethylamine (III)
could not be decomposed by simple boiling of the ether with acetic
anhydride. It had to be heated to 170° to effect this decomposition.
The products were thebaol and ethanoldimethylamine. The former
was identified as an acetyl derivative and the latter as a chloraurate.
On heating either of the phenanthrol ethers (II) or (III) for 5–6
hours with sodium ethylate solution the ethers remained unchanged
and could be recovered quantitatively.
59
**:
A comparison of the physiological effects of a-methylmorphime-
thine and ‘the methylmorphol ether of ethanoldimethylamine (II)
showed that there are both similarities and characteristic differences
between these bases. (Ber. Dtsch. chem. Ges., 1905, 3143.)
. Morphothebaine.
L. Knorr has investigated the nitrogen-free phenanthrene deriva-
tives obtained from morphothebaine. It had been shown previously
that codeinone, an oxidation product of codeine can be converted
into thebenine and its isomeride morphothebaine (Ber. Dtsch. chem.
Ges., 1903, 3074). According to Pschorr and Massaciu (ib. 1904,
p. 714), when thebenine is subjected to exhaustive methylation
trimethoxyvinylphenanthrene is formed which can by oxidized to
trimethoxyphenanthrene carboxylic acid. This proves that in the
morphium alkaloids (morphine, codeine and thebaine) the three
oxygen atoms are all in the phenanthrene nucleus and that the
complex, .CH2.0H2.N(CH3)., is attached to this nucleus by means of
carbon. On applying this reaction to morphothebaine it was found
that in this case too a trimethoxyvinylphenanthrene and a tri-
methoxyvinylphenanthrene carboxylic acid are formed but these were
not identical with the compounds obtained from thebenine. As
thebenine and morphothebaine are formed under almost the same
conditions (the former being formed when 20% hydrochloric acid is
used and the latter when 38% of the same acid is used) the non-
identity of the resulting decomposition products indicates that the
substituents in the reduced phenanthrene nucleus very easily change
their places.
The morphothebaine for this work was prepared by a modifica-
tion of Howard’s method (ib. 1884, p. 527). The so called acid hydro-
chloride obtained by this method (see next paragraph) was con-
verted into the neutral chloride by boiling with alcohol and the free
morphothebaine then liberated by means of sodium carbonate.
When morphothebaine is boiled with benzoyl chloride tribenzoyl-
morphothebaine is formed. As according to Freund (ib. 1899, p. 173)
there are only two OH groups in morphothebaine it must be assumed
that in the benzoylation (the same as in the acetylization) the side
ring containing the nitrogen atom is opened up with the formation
of an NH group which is then substituted by the acyl group. This
assumption is in accord with the fact that these acyl derivatives
60
have no basic properties. The tribenzoylmorphOthebaine crystallizes
from ether-chloroform with one molecule of ether of crystallization.
Dimethylmorphothebaine methine iodomethylate, C22H2SNO3 I,
was obtained either by heating on the water bath the hydrochloride
of the base with methyliodide in presence of sodium methylate in an
atmosphere of nitrogen or by treating morphothebaine iodomethy-
late (ib. 1886, 1596) with dimethyl sulphate in presence of sodium
hydroxide. As three methyl groups enter the molecule of morpho-
thebaine in this reaction it must be assumed that in this case too
the side ring containing the nitrogen atom opens up. That a
‘‘methine” base is formed in this reaction was shown both by analy-
sis and by the evolution of trimethylamine upon heating the product
of methylation with sodium hydroxide.
Besides trimethylamine there is also formed by the action of
alkali upon this product trimethoxyvinylphenanthrene of the same
formula as the trimethoxyvinylphenanthrene obtained by a similar
reaction from thebenine but differing from the latter both in melting
point and behavior towards glacial acetic acid. The compound from
morphothebaine is not affected by boiling glacial acetic acid whereas
that from thebenine is converted under the same conditions into
methebenol. It is supposed that in the trimethoxyvinylphenanthrene
obtained from thebenine the vinyl group is in the Ortho or meso
position to a methoxyl group but that in the compound from
morphothebaine the vinyl group occupies a different position.
The vinyl compound from morphol hebaine decolorizes bromine in
chloroformic solution but the amount of bromine taken up is much
less than one molecule for a molecule of the compound. Besides,
very soon there is an evolution of hydrobromic acid.
On oxidizing the trimethoxyvinylphenanthrene obtained from
morphothebaine with potassium permanganate in acetone solution
trimethoxyphenanthrene carboxylic acid was formed. The acid differs
from the corresponding compound obtained from thebenine in melt-
ing point and from 3.4.6.-trimethoxyphenanthrene—9.—carboxylic
acid previously obtained synthetically by Pschorr (ib. 1902, p. 4406)
in that it does not give off CO2 when heated. It distills without
decomposition under reduced pressure giving a crystalline distillate
which melts only two degrees lower than before the distillation.
Only when kept boiling for a long time the acid breaks up yielding
61
an oily liquid insoluble in alkali. It is supposed that this oily liquid
is 3.4.6—trimethoxyphenanthrene.
(Ber. Dtsch. chem. Ges., 1905, 3153.)
R. Pschorr has succeeded in reducing thebaine to a ketone, the-
bainone. It has been shown previously by Howard that boiling
hydrochloric acid converts thebaine into an acid hydrochloride which
when heated with water, alcohol or dilute hydrochloric acid is
changed into a neutral hydrochloride of morphothebaine. The
splitting open of the “indifferent” oxygen atom in the transformation
of thebaine into morphothebaine (and of morphine into apomorphine)
can be explained by assuming that at first a compound containing
chlorine is formed from which hydrochloric acid is then split off:
N
—C.O.C.H.CH2. -- HCl = –0. (OH) + agº. —) (; H = th + HC1.
/ | | /
It was reasonable to suppose that a similar reaction would take
place on reducing thebaine in presence of hydrochloric acid
N N
—C.O.CH – CH2 + H2 = —C(OH) + CH2 — CH2
/ | / | |
Experiment showed that when thebaine is reduced by means of
tin and hydrochloric acid a compound is obtained which contains
two atoms of hydrogen more than morphothebaine, having the
formula, C1s H21NO3. It contains a phenolic OH, shown by the
solubility in alkali and the formation of a monoacetyl derivative,
and a CO group shown by the reaction with phenylhydrazine,
hydroxylamine and semicarbazide. The compound was named the-
bainone. It contains only one CH3O group showing that in the
reduction of thebaine to thebainone as in the conversion of thebaine
into morphothebaine one CH3O group is saponified. The phenolic
OH of thebainone can be etherified by means of diazomethane. When
treated with methyl iodide in alkaline solution thebainone is con-
verted into the iodomethylate of its methylether which boiling alkali
changes to tertiary methylthebainonemethine. This shows that the
nitrogen in thebainone is tertiary and is contained in a ring. When
this methine base is decomposed, oxethyldimethylamine OH.C2H4...N.-
(CH3)2 is obtained together with 3.4.—dimethoxyphenanthrene
/ To 9 N
&
/T N y^ SN
\–– f*
N2 / \ , = * /
N3 4 / N5 0 /
CH3. () (). CH3
3.4.—Dimethoxyphenanth rene.
(I)
The formation of oxethyldimethylamine shows, that there is in
thebainone a CH3N group and that the nitrogen atom is linked to
a chain of two carbon atoms. The formula of thebainone can there-
fore be resolved as follows: (C14H10O) (O.CH3)(OH)(CH2.0H2.N.CH3).
Hence of the three oxygen atoms of thebainone one is phenolic,
one is in the form of a CH30 group and one in the form of a CO
group. Consequently there can be no “indifferent” oxygen atom in
thebainone.
The position of the oxygen atoms in thebainone is indicated by
the 3.4.— dimethoxyphenanthrene obtained from methylthebainone-
methine and by the synthesis of acetyl thebaol quinone accomplished
by Pschorr and Stöhrer
O ()
/To Tº, N
/ N
/1 N /TT3N
^2 \—’ 7
N / N /
N 3_ _4/ Nº. 6/
CH3.O O O.CH3
|
CO.CH3
Acetyl theba,ol quin One.
(II)
This synthesis proves that in thebaine the two CH3O groups are
in positions 3 and 6 and the “indifferent” oxygen atom in 4. Hence
in thebainone
(C14H10O) (O.CH3)(OH)0H2.0H2.N.CH3)
the CH3O group is in 3 and the OH group which corresponds to the
“indifferent” oxygen atom of thebaine in 4. The CH3O situat, d in
thebaine in 6 is saponified in the conversion of thebaine into the-
bainone. In methylthebainone, (C14H10O)(O.CH3)2(CH2CH2.N.CHs),
one CHAO group must be in 3, the other in 4 and the ketonic oxygen
63
atom in 6. In the conversion of thebaine into thebainone the CH3O
group in 6 is first converted into an OH group which then changes
to a CO group. This is also proven by the fact that thebainone
can be made from codeinone in which the position of the CO group
is known to be in 6. By assigning to thebaine a formula similar to
the one assigned by Pschorr to morphine the conversion of thebaine
into thebainone can be represented as follows:
H2 N.CH3
/º / N / N
/. N / N / NCH2
| | | | |
3 |
CH3. O 4. /N N /CH2
Nº. J/ N / ——).
| Sh
o-Z", a /CH
/ §ſ
H O.CH3
Thebaine.
H2 N.CH3
H2 N.CH3 N /N / N
S. Z N /N / N / N / NCH2
/* N / N / NCH2 | | |NH
| | | " | cº-d / º ºn
Ny’s /NJºch, , chºov Jº Jºch,
/ N/ N / HO |NH
CH3. O | NH | |
: H2N / CH2
H2 N CH N /
J/ |
HO l O
Intermediote Product. Thebain One.
(III) (IV)
The thebainone was prepared by heating thebaine with strong
hydrochloric acid and stannous chloride in a closed vessel on the
water bath for 15–20 minutes. After making the liquid alkaline
with sodium bicarbonate the tin was removed by means of a centri-
fugal machine the liquid filtered through charcoal and the thebainone
shaken out with chloroform. After drying the chloroformic solution
with calcined sodium sulphate, distilling off the solvent and rubbing
up the residue with methyl alcohol the whole mass became crystal-
line.
64
From water thebainone crystallizes in almost colorless plates
melting at 89–90°. From methyl alcohol it crystallizes in slightly
yellowish prisms containing one molecule of methyl alcohol of
crystallization and melting at 115–118°. The methyl alcohol in the
crystals could not be determined by drying without decomposition
of the substance, but was determined by a methoxyl estimation.
Thebainone is difficultly soluble in water and the solution has a
yellowish color which changes to an intense red on addition of
sodium hydroxide. The red color is destroyed by hydrochloric acid.
When treated with strong sodium hydroxide (33%) thebainone gives
a sodium salt in form of yellowish-red shining plates which could
not be recrystallized. With picric acid in alcoholic solution the-
bainone forms a picrate which is decomposed by ammonia into its
component parts. An oxime of thebainone was obtained by digesting
a solution of thebainone in dilute acetic acid with hydroxylamine
hydrochloride and sodium acetate and then adding a strong solution
(50%) of potassium carbonate. From a mixture of ethyl acetate
and petroleum ether the oxime crystallizes in almost colorless
prisms. When recrystallized from methyl alcohol the crystals con-
tain one molecule of methyl alcohol of crystallization. A semicarba-
Zone of thebainone was obtained in the same way as the Oxime.
From acetic ether the semicarbazone crystallizes in colorless needles
containing one molecule of the solvent of crystallization which is
partly given off on standing in the air. A hydrazone of thebainone
could not be obtained in crystalline form.
On boiling a solution of thebainone in a mixture of alcohol and
ethyl acetate with an excess of methyl iodide thebainone is converted
into its iodomethylate which was recrystallized from a mixture of
methyl alcohol, acetic ether and a few drops of ether.
By boiling thebainone with acetic anhydride, diluting the liquid
with water and making alkaline with strong potassium carbonate
solution (50%) acetyl thebainone was obtained which was recrystal-
lized from a mixture of ether and petroleum ether. The acetyl the-
bainone can be reconverted into thebainone by boiling the acetyl
compound with sodium hydroxide, saturating the solution with car-
bon dioxide and shaking out the thebainone with chloroform. An
iodomethylate of acetyl thebainone was prepared by boiling a solu-
tion of the acetyl compound in acetic ether with methyl iodide. The
same iodomethylate is formed on heating the thebainone iodo-
65
methylate with acetic anhydride to solution and precipitating the
iodomethylate with ether. While it was possible to convert the
acetyl thebainone into a phenylhydrazone no oxime of the compound
could be prepared. On subjecting acetyl thebainone to the same
reaction by which thebainone oxime was prepared the acetyl com-
pound loses the acetyl group and is converted into thebainone
O XIII 162.
When thebainone, dissolved in dilute sodium hydroxide, is shaken
with sodium amalgam it is reduced to an alcohol thebainol which
separates out as a resinous mass when the liquid is saturated with
carbon dioxide. From methyl alcohol thebainol crystallizes in pris-
matic needles which melt at 54–55°. After melting in vacuum the
solidified mass loses about two per cent in weight and melts at
76–78°.
The methyl ether of thebainone was made by treating an alco-
holic solution of thebainone with an ethereal solution of diazo-
methane. On boiling thebainone with methyl iodide in presence of
sodium methylate the thebainone is converted into the iodomethylate
of methyl thebainone. The same compound can be obtained by
boiling an alcoholic solution of methyl thebainone with methyl
iodide.
Methyl thebainone methine was prepared by warming methyl
thebainone iodomethylate with a 30% solution of sodium hydroxide
and taking up the oily methine base which separated out with ether
By digesting methyl thebainonemethine with methyl iodide the iodo-
methylate of methyl thebainonemethine was obtained. The iodo-
methylate crystallizes with a molecule of alcohol of crystalliza-
tion.
The methyl thebainonemethine was converted into a semicarba-
zone which crystallizes from alcohol with a molecule of alcohol of
crystallization and into a hydrochloride of the oxime of methyl the-
bainonemethine. The free oxime could not be obtained in crystalline
form. (Ber. Dtsch. chem. Ges., 1905, 3160.)
L. Knorr and R. Pschorr have investigated the decomposition
products of thebainone. On comparing the formulas of codeinone,
thebain One, morphOthebaine and thebenine it can be seen that the-
bain one occupies an intermediate position between codeinone on one
hand and morphothebaine and thebenine on the other,
66
—O.CH3 —().CH3 —(). CH3 —O.CH3
X-O | —OH —OH —OH
C14H4(H5) =ºn, cutiºn, Cºha(H2)}T3:... Cºhº Tºº,
—sch, |-sch, —N.CH3 NH.(H3
Codein One. Thebain One. Morph othebaine Thebenino.
It resembles the latter two in containing a phenolic OH group
instead of the “indifferent” oxygen atom. On the other hand the-
bainone differs from the purely aromatic thebenine and the dihydro-
system of morphothebaine in being derived from a hexahydro-
phenanthrene. The degree of reduction of the phenanthrene nucleus
seems to exercise an influence upon the nature of the decomposition
products. When methyl thebainonemethine is heated with acetic
anhydride the same decomposition products are obtained as from
methylmorphimethine, thebaine or codeinone, namely, oxethyl-
dimethylamine, OH.C2H4...N(CH3)2 and dimethyl morphol. When
heated with sodium ethylate methyl thebainonemethine yields ethyl-
dimethylamine along with two phenanthrene derivatives which could
not be completely identified. *
Upon heating methyl thebainonemethine methyl hydroxide tri-
methylamine is evolved but no ethylene is formed as in the case of
£8-methylmorphimethine.
The authors give a table of the decomposition products obtained
by various authors from the morphium alkaloids (morphine, codeine
and thebaine).
The formation of oxethyldimethylamine from thebainone which
does not contain an “indifferent” oxygen atom shows that the
appearance of the alcohol bases among the decomposition products
of these alkaloids does not prove the presence of an “indifferent.”
oxygen atom which links the group, CH2CH2NCH, to the
phenanthrene nucleus. It is most probable that the hydramines are
secondary products of unsaturated bases formed at first in the
reactions.
The constitution of the morphium alkaloids as shown by the
results of the latest experiments, seems to be as follows:
1. Morphine, codeine and thebaine are derivatives of 3.6.-dioxy-
phenanthrylene oxide
()
/N
/
HO / N ().H
/GT5 N / HT3°N
/ 2\
N / N /
\——’ N - 1/
N /
N /
3.6.-Dioxyphenanthrylene Oxide.
In morphine both OH groups are free, in codeine one of the OH
groups is methylated, in thebaine both OH groups are methylated.
2. To the three rings of the phenanthrene molecule is linked the
complex, .CH2.0H2.N.CH3, as a side ring. The linking is either by
the a or 8 carbon atom of this complex, i. e., either as
.N.CH3 OT 8, S .N.CH3
,(XH.CH3 ..CH2.0H2
The positions on the phenanthrene nucleus to which this complex
is attached is not yet definitely settled. The nitrogen atom of this
complex is either in a reduced quinoline, or a reduced isoquinoline,
or a pyrrolidine ring. The experimentally established constitution
of papaverine would seem to indicate the presence of an isoquinoline
nucleus in the morphium alkaloids.
/N / N
CH3. O/ N / N
| | 1 |
|
(H3.ON / N N / N
N / N.CH2 N / N
| | II |
/ N / N /N / N
CH3, () Z N / NN / N / N
| | | | III
("H 3.ON / N / N / N /
N / N / N / N /
Papaverine. Nucleus of Morphium Alkaloids.
3. Thebaine is derived from a tetrahydrophenanthrene. The six
additive hydrogen atoms of morphine are in the rings II and III,
the ring I is a pure benzol ring and to it is attached the phenolic
68
OH group. The complex, .C2H4...N.CH3, is linked to the reduced part
of the morphium alkaloids. They can therefore be represented as
follows:
—OH (3) Y-99H8 (3) —O.CH3 (3)
>O (4 and 5) >O (4 and 5) >O (4 and 5)
(hali, Ho! &#!"n) Cºtti,(Ho)}~8;"ſm (whº(H,)}~8;"?
...| | .."
—N.CH3 l ; J–N.CHs | | —N.CH3 l ;
Morphine. CO deine. Thebaine.
The decomposition of methyl thebainonemethine into dimethyl-
morphol and oxethyldimethylamine was carried out by heating the
methine base with acetic anhydride for 48 hours to 170–180°,
pouring the product into hot water and extracting the phenanthrene-
derivative with ether. The liquid was then made alkaline with
sodium hydroxyde and the hydramine distilled over with steam.
The dimethylmorphol was identified by analysis, its melting point,
its picrate and dibromide.
The oxethyldimethylamine was identified by its chloraurate.
On heating methyl thebainonemethine with sodium ethylate to
150–160° it was decomposed into ethyldimethylamine and two
phenanthrene derivatives of which one was soluble the other insoluble
in alkalies. The ethyldimethylamine was identified by comparing the
base and its chloraurate with compounds made synthetically.
On converting the iodomethylate of methylthebainonemethine
into the corresponding ammonium base and then heating the latter,
trimethylamine was evolved (identified as a chloraurate). As no
ethylene was evolved as is the case with methylmorphimethine
methylhydroxide it must be assumed that the nitrogen-free
decomposition product of the methylthebainonemethine methyl
hydroxide was a vinylphenanthrene. In this vinyl compound the CO
group of thebainone seems still to be present as the compound is
capable of forming a semicarbazone and a phenylhydrazone.
(Ber. Dtsch. chem. Ges., 1905, 3172.)
Nicotine.
F. Ratz finds that nicotine cannot be obtained in perfect purity
by fractional distillation in vacuum in a current of hydrogen. The
best way to prepare pure nicotine is to convert it into the double
69
salt, nicotine .2HCl.ZnCl2 + H2O, recrystallize the compound from
hot water, liberate the alkaloid from the salt by means of potassium
hydroxide and then subject it to fractional distillation in vacuum in
a current of hydrogen. Thus purified nicotine boils at 246.2° under
a pressure of 719.8 mm. and has the specific gravity 1.00924 and
the specific rotation [a]p20 = –169.22. As this specific rotation of
pure nicotine is about 8° degrees higher than the rotation previously
found by Landolt, there must have been about 5% impurities in
Landolt's nicotine. These impurities could not have been made up
exclusively of nicotimine (Ber. 34, 696) as of this base there is only
about 0.5% in ordinary nicotine. It is possible that Landolt's
nicotine contained either some other bases isomeric with nicotine or
some racemized nicotine. The latter supposition is made probable
by the observation of Pictet and Rotschy (Ber. 33, 2353) according
to which nicotine is easily racemized by heating the aqueous solution
of its sulphate or hydrochloride. (Monatsh. 1905, 1241.)
Oxys parteine.
Acco.ding to F. B. Ahrens oxysparteine, C15H24N2O, can be ob-
tained in quantitative yield by adding an alkaline solution of
potassium ferricyanide to sparteine till the alkaloid goes into solu-
tion and further addition of ferricyanide does not change color. As
long as there is unchanged sparteine the color of the oxidizing agent
changes to wine yellow. The oxysparteine is then extracted from
the liquid by shaking with ether or chloroform.
(Ber. Dsch. chem. Ges., 1905, 3268.)
Papaverine.
According to H. Decker a nitro derivative of the quaternary
papaverinium salts can be obtained by treating the addition product
of papaverine and dimethyl sulphate with nitric acid (1.3) at a
temperature of 35–40°. The NO2 group goes into the same position
which it occupies when papaverine itself is nitrated. By means of
potassium iodide the nitrated dimethyl sulphate compound can be
converted into the corresponding iodomethylate. On adding alkali
to a hot solution of the nitro compound it breaks up into nitro-
homoveratrol and dimethoxymethylisoquinolone.
(Ber. Dtsch. chem. Ges., 1905, 1279.)
By comparing the oxidation products of dimethoxyisoquinoline
of known constitution with the N-alkyldimethoxyisoquinolones formed
70
in the oxidation of isopapaverine bases, H. Decker and O. Koch have
corroborated their conclusions previously arrived at about the con-
stitution of the latter compounds. (Br. Dtsch. chem. Ges., 1904,
520 and 1397.) In this way the compound obtained by converting
dimethoxyisoquinoline into an iodomethylate and then oxidizing the
latter by means of potassium ferricyanide was found to be identical
with one of the products of Oxidation of isopapaverine. Both com-
pounds must therefore have the constitution of an N-methyldimeth-
oxyisoquinolone,
/ N /
clo/ N/
|
CH3. () / N /N.CH:
/ `N /
|
()
N-Methyldinnethoxyisoquinolone.
Another compound obtained in the oxidation of isopapa verine
was found to be identical with the compound obtained by digesting
dimethoxyisoquinoline with benzyl chloride for six hours at 100° and
then oxidizing the product with potassium ferricyanide. Hence the
constitution of both must be that of an N-benzyldimethoxyiso-
quinolone. (Ber. Dtsch. chem. Ges., 1905, 1739.)
Pilocarpine.
A. Pinner continues his investigations on the constitution of
pilocarpine. In previous articles it was shown that the alkaloid
contains a glyoxaline ring combined with a lactone ring (I)
C2H5—CIl-——CH-CH2—C–N.CH3
NCH
-*
('O—O—CH2 (, H–N
(I)
Owing to the easy conversion of pilocarpine into isopilocarpine
the constitution of pilocarpine cannot be established with certainty.
As to isopilocarpine its constitution must be as follows (II):
C2HB-CH-CII—CH2—C–N
| - |
| |
C()—()— ('H2 CH-N.CH:
S CH
/
(II)
71
This is shown by following facts. When isopilocarpine is heated
with soda-line methylglyoxaline of the following constitution is
formed :
(H–N
~ ("H
/
(!II — N.('Ha
When dibromisopilocarpine is oxidized pilopinic acid, Cs H11NO4,
is obtained which on further oxidation gives among other products
ammonia but no methylamine. The eighth carbon atom of pilopinic
acid must therefore be linked to a nitrogen atom which is not linked
to a CH3 group.
The conversion of pilocarpine derivatives into isopilocarpine
derivatives cannot be accounted for by stereoisomeric considerations
because stereoismerism being possible only in the lactone part of the
pilocarpine molecule there ought to be formed iso compounds from
pilocarpine derivatives only as long as this lactone part remains
intact regardless of the presence or absence of the glyoxaline part.
But as a matter of fact the iso-compounds all contain the glyoxaline
ring and the isomerism disappears with the destruction of this ring.
Hence the isomerism must be accounted for by assuming that either
one or the other of the three CH groups of the glyoxaline ring is
linked to the lactone part of the molecule.
For pilocarpoic acid, C11 H16N2O5, obtained by oxidizing pilo-
carpine with chromie anhydride the following constitution is pro
posed (III):
('e H5.('H–C'H–('H2—C–N CH3
XCO
()()2 II CO2 II UH–NH
Pilocarpoic Acid.
(III)
This is shown by the fact that when pilocarpoie acid is further
oxidized by potassium permanganate an acid is obtained which was
identified by Jowett as ethyltriearballylic acid, C2H5.0 H.(CO2H).C.H.-
(CO2H).CH2.(CO2H), together with methylurea, CO. (NH2)(NH.CH3).
Hence we must assume that in the oxidation of pilocarpine to the
dibasic pilocarpoic acid the CH2 group of the lactone ring is oxidized
to a CO2H group and the carbon atom of the glyoxaline ring linked
to the two nitrogen atoms is converted into a CO group.
72
On decomposing the barium salt of pilocarpoic acid with sul-
phuric acid a substance was obtained which had the formula,
C11H14N2O4, and was shown to be the anhydride of an acid,
C11 H16N2O5, isomeric with pilocarpoic acid. The acid was named iso-
pilocarpoic acid and is supposed to have the following constitution :
C2H5.0H–CH-CH2—C-—NH `s
| |
/
|
| |
('O2H ('O2 H CH-(N.CH3)
Isopilocarpoic Acid.
(IV)
The anhydride, C11H14N2O4, can be converted into isopilocarpoic
acid by heating the anhydride to 200–210° for half an hour and
then recrystallizing from water. It is supposed that the trans-
formation of pilocarpoic acid into isopilocarpoic acid is of the same
nature as the transformation of pilocarpine hydrochloride into iso-
pilocarpine hydrochloride.
When pilocarpoic acid (III) is oxidized with potassium perman-
ganate an acid is obtained which had been previously named pilo-
malic acid and supposed to correspond to the formula, C7H12O5. It
is shown that this acid is identical with ethyltricarballylic acid and
has the formula, Cs H12O6. The name pilomalic acid should therefore
be applied only to the acid of the formula, C7H12O5, obtained by
the action of bases upon pilopic acid.
The successive steps in the oxidation of pilocarpine and isopilo-
carpine are supposed to be as follows: Both alkaloids have the
formula C7H1 102–04H8N2 which is made up of a lactone group and
a glyoxaline radicle. In the oxidation with potassium permanganate
or hydrogen peroxide two OH groups attach themselves to the two
carbon atoms which in the glyoxaline ring are linked to each other
by a double binding forming an intermediate product (W)
(*H, Os–COH)—N.CHAN
NCH
CH (OH)——N
(V)
which is then further oxidized to (W1)
("Hºoº-ºoH)—NCH3N
| OO
—NH’
CO
(VI)
73
The compound (WI) then breaks up into CO2, NH3, NH2.CH3
CO (NH2)(NH.CH3) and the acid (VII)
C2 H-ſh–H–Chicon
| |
CO—O—CH2
(VII)
In presence of alkali this lactone acid (VII) is then converted
into homopilomalic acid
on-ºn-ºn—ch.com
| |
CO2H CH2.OEI
Homopilomalic Acid.
If the oxidation is carried out by means of chromic anhydride
both the lactone group and the glyoxaline ring are oxidized giving
pilocarpoic acid (III). The potassium permanganate then oxidizes
pilocarpoic acid to ethyltricarballylic acid,
cº-ºh-ºh-ºh-ooh
| |
CO2H CO2H
Dibromisopilocarpinic acid, C11H14Br2N2O4, which is obtained by
the action of bromine and water at 100° on isopilocarpine is very
easily affected by bases. Even at Ordinary temperature bases split
off both bromine atoms with the formation of volatile compounds.
Barium hydrate decomposes the brominated acid into barium oxalate,
harium carbonate, ammonia, methylamine, methylurea and barium
pilomalate, C7H10O3.Ba.H2O.
Bromocarpinic acid, C11H15BrN2O4, which is obtainsd from pilo-
carpine by a method similar to the one by which dibromisocarpinic
acid is obtained from isopilocarpine is not easily affected by alkalies.
Barium hydrate decomposes it only when heated with it to 130° to
140° for 8–10 hours. The products are: barium bromide, ammonia,
methylamine, barium pilomate and barium carbonate but no barium
oxalate is formed. The fact that dibromisopilocarpinic acid yields
barium oxalate whereas brompilocarpinic acid does not is accounted
for by the assumption that in the former the two adjacent carbon
atoms of the glyoxaline ring are still linked to each other but are
separated in the latter acid. The constitution of these two acids
would therefore seem to be as follows:
74.
C2H5OH−OH.Br. C. Br—NH C2H5.0H–CH.CHBr, CO-N.CH3
| | | >co
CO. O. CH2 CO—N.CH3 CO. O. CH2 NH2—CO
Dibromisopilocarpinic Acid. Brompilocarpinic Acid.
For isopilocarpinolactone, C11H16N2O5, obtained by reduction of
dibromisopilocarpinic acid, the following constitution is proposed
C2H5.0H-—CH-CH2—C(OH)—NH
XCO
CO—O—CH2 CO—N.CH3
Isopilocarpinolactone.
For the compound which is obtained from isopilocarpinolactone
by the elimination of one molecule of water the following constitution
is suggested.
C2H5. CH-CH-CH=C–N H
| | XCO
CO—O—CH2 CO—N.CH3
The isopilocarpininic acid which Jowett obtained by the action
of bromine upon isopilocarpine in the cold probably has the follow-
ing constitution:
C2H5.0H–CH-CH2—0—NH
| XCO
CO—O—CH2 C(OH)—N.CH3
Isopilocarpininic Acid.
By intramolecular rearrangement this acid probably changes to
a ketone of the following constitution:
C2H5.0H-—CH-CH2—CH-NH
| XCO
CO-O-CH2 CO—N.CH3
On treating isopilocarpoic acid (IV) or the anhydride of pilo-
carpoic acid (III) with alcohol and sulphuric acid a diethyl ester of
isopilocarpoic acid, C11H14N2O5(C2H5) is formed. The ester, an
oily liquid, is not affected by ammonia and forms a hydrochloride
and a chloroplatinate.
If an excess of ethylbromide and two molecules of potassium
hydroxide be made to react on pilocarpoic acid the same ester is
formed together with the brommethylate of the ester.
75
The ethyltricarballylic acid obtained by oxidation of pilocarpoic
acid (III) with potassium permanganate melts at 145–146°, not at
157° as given by Jowett for the same acid obtained by melting
homopilopic acid with potassium hydroxide. The difference in the
melting points of the acid is possibly due to the fact that Jowett's
acid is optically inactive whereas the acid obtained by the author is
active. Upon warming a solution of the calcium salt of ethyltri-
carballylic acid the whole liquid solidifies to a jelly which becomes
liquid on cooling.
A triethylester of tricarballylic acid, CaFI5(CO2.02H5)3, was pre-
pared by the action of ethylbromide and potassium hydroxide upon
the acid at 100°. The ester is not affected by heating it for 10
hours to 100° with a solution of ammonia in methyl alcohol, but if
the heating be continued for 72 hours the ester is converted into
the corresponding triamide, CaFI5(CO.NH2)3.
The author obtained a perbromide of monobromisopilocarpine,
C11H15BrN2.05.H.Br. Brz, but the exact conditions under which it is
formed could not be established. The perbromide differs from the
perbromide of dibromisopilocarpine in that it is not affected by
heating it with bromine and water which conditions convert the
latter into dibromisopilocarpinic acid.
Ber. Dtsch. chem. Ges., 1995, 1510.
According to A. Pinner when pilocarpine hydrochloride is heated
to 225–235° for 1 to 2 hours it is converted into an isomeric com-
pound named metapilocarpine. From pilocarpine and isopilocarpine
(which is obtained by heating pilocarpine only for a short time to
100°) metapilocarpine differs in the following points: Isopilocarpine
is soluble in chloroform, metapilocarpine is not. The salts of meta-
pilocarpine, including the nitrate, are not crystalline. The crystalline
form of the chloroplatinate of metapilocarpine is different from the
crystalline form of the chloroplatinates of pilocarpine and isopilo-
carpine. When either metapilocarpine or its N-alkyl derivatives are
boiled with potassium hydroxide only one nitrogen atom is eliminated
as methylamine and the acids formed in the reaction still contain
nitrogen, whereas non-alkylized pilocarpine or isopilocarpine are not
so easily decomposed by potassium hydroxide and in the reaction
both nitrogen atoms are eliminated, the acids obtained being free
from nitrogen. The formulas of the salts of metapilocarpine are
identical with those of pilocarpine and isopilocarpine but in the free
76
condition metapilocarpine contains the elements of one molecule of
water more than the other two alkaloids. The water is not eliminated
at 102°.
C11H16N2O2 C11H1sN2O3 or C11H16N2O2.H2O
Pilocarpine or Isopilocarpine. Metapilocarpine.
(Ber. Dtsch. chem. Ges., 1905, p. 3560.)
H. A. D. Jowett has succeeded in converting isopilocarpine into
pilocarpine by boiling the former with alcoholic potassium hydroxide
and separating the bases from each other by fractional crystallization.
As it is alcoholic potassium hydroxide which changes pilocarpine
into isopilocarpine it must be assumed that the two bases do not
differ from each other structurally but are steroisomerides and that
when either of them is treated with alcoholic potassium hydroxide
a state of equilibrium results. If the alkaloids were structurally
different one of them, namely, isopilocarpine would have to be
supposed to possess greater stability under the conditions of experi-
ment and a reverse conversion of isopilocarpine into pilocarpine
ought not to be possible. The constitution of the alkaloids would
therefor seem to be as follows:
+ + — +
C2H5.0H.C.H.CH2. C.N(CH3) C2H5.0H.C.H.CH2.0.N(CH)
| | N N c.
| 2CO 2CO
CO CH2 XH--N CO CH2 CH N
N / N/
O O
Pilocarpine. ISO pilocarpine.
The arguments brought forward in favor of structural isomerism
the author has answered in previous articles. Pinner has lately
advanced the argument that if the bases were stereoisomerides, the
isomerism not being in the glyoxaline complex must be in the group
C7H1102, hence we ought to get by oxidation isomeric not identical
compounds whenever the group C7H1102 is present, whereas as a
matter of fact, one always obtains isomeric compounds from pilo-
carpine and isopilocarpine as long as the glyoxaline ring remains
intact. As soon as compounds are formed in which this group no
longer exists we get identical compounds no matter whether pilo-
carpine or isopilocarpine is taken. Thus both alkaloids yield upon
oxidation the same homopilopic acid.
77
The author refutes this argument by assuming that the products
are really different at first but are changed to the isoform by the
action of alkali or by passing through their esters in the purification
of the compounds. (Journ. Chem. Soc. 1905, 794.)
Piperine.
Following color reactions for piperine have been devised by C.
Reichard. On adding hydrochloric acid to a mixture of powdered
copper sulphate and piperine a light green color is developed which
soon changes to dark green. A mixture of piperine and copper oxy-
chloride dissolves in ammonia with a deep blue color. On evaporat-
ing the solution to dryness and adding hydrochloric acid to the
residue an uranium-green color is developed.
Hydrochloric or sulphuric acids color piperine yellow.
On adding a little water and a crystal of mercurous nitrate to
a crystal of piperine the mercurous nitrate crystal remains colorless
while the piperine crystal assumes a yellow color which changes to
red upon addition of concentrated sulphuric acid. A mixture of
mercuric chloride and piperine is colored yellow by water.
A concentrated solution of antimony trichloride colors piperine
yellow. A concentrated solution of bismuth chloride also colors
piperine yellow but after awhile a brownish-red precipitate separates
Out.
A concentrated solution of potassium sulphocyanate becomes
yellow upon addition of a crystal of piperine and some hydrochloric
acid. The color of the solution disappears very soon while the
piperine crystal retains the yellow color.
A mixture of piperine and sodium vana.date becomes yellow upon
addition of water. “On evaporating the liquid to dryness and adding
hydrochloric acid the yellow color changes to red-brown.
A mixture of piperine and titanic acid (TiO2) is colored by sul-
phuric acid in the cold either brown, or black or dark green.
A mixture of piperine and a-nitroso-8-naphtol is colored yellow
by hydrochloric acid. On evaporating to dryness a brownish residue
is left.
a-Naphthol or a-naphtylamine sulphate are colored yellowish-
green by hydrochloric acid in presence of piperine.
(Pharm. Centr.-H., 1905, 935.)
78
Pseudopelletierine.
R. Willstätter and H. Weraguth have investigated some decom-
position products of pseudopelletierine or N-methylgranatonine
º CH CH2
| |
ºh, Ach. ("O
CH2 CH--CH2
Pseudopelletierine (N-Methylgranatonine).
As this alkaloid is a homologue of tropinone it ought to be
possible to obtain from it unsaturated cyclic compounds with eight
carbon atoms in the same way as unsaturated seven-membered
cyclic compounds are obtained from tropine. Using the methods
which proved valuable in the tropine series the authors succeeded in
obtaining from pseudopelletierine cyclooctadiène and cyclooctatrième
but no cyclooctotetraëne could be obtained. The latter would be
of particular interest owing to the similarity in structure with
benzene.
Cyclooctadiène, CsPI12, was made by subjecting N-methylgranat-
anine to exhaustive methylation. In the first stage of the reaction
the nitrogen “bridge” of the molecule breaks open forming des-
dimethylgranatanine methylammonium hydroxide which upon distill-
ation breaks up into water, trimethylamine and cyclooctadiène
N. (CH3)3.OH
gº-º-º: th-ch—ºn.
| |
CH2 N.CH3 CH2 —X CH2 CH2 —x H2O + (CH3)3N + Cs H12
| t i | | Cyclooctadiène.
CH2—CH-CH2 CH2—OH−-CH
N-Methylgranatanine. Des-dimethylgranatanine
methylammonium hydroxide.
The cyclooctadične has great tendency to polymerize. Upon gentle
warming, it is partly converted with explosive violence into dicyclo-
octadiène. It is easily affected by potassium permanganate and
readily combines with bromine. Hence the hydrocarbon, C8H12,
previously prepared by Doebner not reacting with pot assium per-
manganate and not combining with bromine cannot be a cycloocta-
diêne but must be a saturated hydrocarbon made up of three rings.
The position of the double bindings in the cyclooctadiène has
79
not been established. According to the mode of formation it ought
to have either one or the other of the following formulas:
gh-oh-ºh CH == ch—ºn.
|
th. gº. OI’ th. º
|
CH2—OH==CH CH2—CH==CH
But as in the formation of piperylene from piperidine and of
cycloheptadiène from tropane the double binding changes to the
conjugated position it is possible that cyclooctadiène has the follow-
ing structure:
ºh-oh-ºh
CH2 CH
|
H2—CH2—CH
Cyclooctatriéne, C8H10, was prepared by converting cycloocta-
diène into its dibromide and heating the latter with quinoline to
to 120–130°. Attempts to prepare cyclooctatriéne directly from
N-methylgranatenine by means of exhaustive methylation showed
that in this reaction only a ketone, Cs H12O, is formed, not a hydro-
carbon
CH2—0H–CH
| | |
CH2 N.CH3 CH
| | |
CH2—CH-—CH2
N-Methylgranatenine
The cyclooctatriéne could not be obtained in pure eondition. It
has an agreeable odor, does not polymerize but resinifies on exposure
to the air.
Cyclooctadiène, CsPI12, is an oily liquid of a strong penetrating
odor and is very poisonous. In alcoholic solution it is colored
orange by sulphuric acid. (Ber. Dtsch. chem. Ges., 1905, 1975.)
In a continuation of the preceeding research R. Willstätter and
H. Weraguth have investigated some derivatives of pseudopelletierine.
N-methylgranatanine could not be prepared by reducing N-methyl-
granatonine with zinc and sulphuric acid but was prepared by re-
ducing the ketone electrolytically in acid solution. The N-methyl-
granatanine was separated from two stereoisomeric N-methylgra-
natolines which are also formed in the electrolytic reduction by
Setting the bases free with alkali and distilling with steam. From
80
the distillate the N-methylgranatanine was shaken out with ether
and after drying with potassium hydroxide redistilled. N-methyl-
granatanine melts at 55–58°, is not affected by potassium perman-
ganate in presence of sulphuric acid and does not reduce silver nitrate
at water bath heat.
N-methylgranatanine methylammonium hydroxide was prepared
by adding freshly precipitated silver oxide to a boiling aqueous
solution of the iodomethylate of the base. The hydroxide contains
about 16 molecules of water, melts when gently heated and effloresces
in dry air. The anhydrous base is hygroscopic.
When this base is distilled 44-des-dimethylgranatanine is obtained
N(CH3)2
|
CH2—CH-CH2
| |
CH2 CH2
|
CH2—CH=CH
A 4-des-Dimethylgranatanine.
When thus obtained the des-dimethylgranatamine is contaminated
with N-methylgranatanine formed in the reaction by splitting off
methyl alcohol from the ammonium base. The des-base can be
separated from the N-methylgranatanine by treating their iodo-
methylates with chloroform (in which the N-methylgranatanine com-
pound is insoluble), then converting the iodomethylate into the
corresponding chloromethylate and distilling the latter.
The 44-des-dimethylgranatanine is a colorless oil of a narcotic
odor and is volatile with steam. It is miscible with alcohol and
ether and is less soluble in warm than in cold water. It is unstable
towards potassium permanganate in presence of sulphuric acid and
is not reducible by sodium and alcohol. It forms a picrate, a chloro-
platinate and an iodomethylate. The latter is soluble in water,
alcohol or chloroform.
In the electrolytic reduction of N-methylgranatonine there are
formed besides N-methylgranatanine two stereoisomeric N-methyl-
granatolines
CH2 ºn—ºn.
| |
º Nch. CH.OH
|
CH2 CH-CH2
N-methylgranatolines.
81
One of the stereoisomers melts at 100° and is identical with the
compound previously prepared by Cimiacian and Silber. It was
named ps-methylgranatoline.
The other stereoisomer melts at 69° is more easily oxidized back
to the ketone by chromic anhydride and is more readily affected by
potassium permanganate in presence of sulphuric acid than the
ps-compound. The lower melting N-methylgranatoline when boiled
with sodium and amyl alcohol is changed to ps-methylgranatoline.
On subjecting the ps-base to exhaustive methylation a mixture
of two isomeric des-ps-dimethylgranatolines was obtained. They
were separated from unchanged ps-methylgranatoline by means of
petroleum ether and from each other by fractional distillation one
boiling at 141–142°, the other at 234.5–238.5°. The presence of
an OH group in the higher boiling granatoline was shown by
benzoylation.
On warming the higher boiling alkamine with a mixture of phos-
phorus pentachloride and phosphorus oxychloride it is converted
into ps-methyl-3-chlorgranatanine. By a similar reaction tropine is
converted into 3-chlortropane.
CH3 CH-CH2 ("He CH-CH2
th. kch. th.c. | sch, the
th. th—th. CH2 (H–CH2
3-Chlor-N-methyl-granatoline. 3-Chlor tropane.
(Ber. Dtsch. chem. Ges. 1905, 1984.)
Quinine.
According to A. Kalâhne when quinine sulphate is heated between
temperatures of 100° and 180° or by cooling again between these
temperatures the salt emits light for a short time and the surround-
ing air becomes ionized. The phenomenon is due to the loss or
gain of water and varies with the temperature and vapor tension of
the surrounding medium. The rays emitted are either a- or -ultra-
violet rays. (Physik. Zeitschr. 1905, 778.)
H. Fühner shows that, as the thalleioquin reaction is given not
only by quinine which contains a CH3O group but also by cupreine
82
which contains an OH group in place of the CH3O group in quinine,
the reaction cannot depend upon the presence of a quinanisol complex
but must be given by all paraguinoline derivatives. It was found
that when chlorine is passed into an ice-cold solution of paraoxy-
quinoline hydrochloride a dichlorparaoxyquinoline is formed which
when treated in solution with ammonia gives a green or blue color.
If in the reaction with chlorine Y-oxyquinoline be taken instead of
the para compound the resulting chlorine derivative gives the thall-
eioquin reaction only when the ammonia is added to the dry residue,
not to its solution. (Ber. Dtsch. chem. Ges., 1905, 2713.)
According to M. P. Guigues quinine salts are insoluble in
ammonium salt solutions. Hence any salt of quinine can be pre-
pared by dissolving the alkaloid in the corresponding acid and add-
ing the ammonium salt of the same acid to the solution. The quinine
salt soon crystallizes out.
If sulphate of quinine be dissolved in water and ammonium
tartrate or ammonium oxalate added to the solution pure quinine
tartrate or oxalate crystallizes out. If to a solution of quinine sul-
phate a salt of ammonia with another acid than sulphuric he added
the alkaloidal salt which crystallizes out consists of a mixture of
Quinine sulphate and a quinine salt of that acid the ammonium
salt of which was used. (J. Phar. Chim., 1905, 303.)
Scopoline.
E. Schmidt has investigated the constitution of scopoline. The
author had previously shown that barium hydroxide decomposes
scopolamine into scopoline and atropic acid
C17H21 NO4 == C8H13NO2 + Co. HsO2
Scopolamine. Scopoline. A tropic acid.
As atropine and hyosciamine which are nearly related to scopol-
amine break up under the same conditions into tropine and atropic
acid
C17H23NO3 == Cs H15.NO + Co. H8O2
Atropine. Tropine. A tropic acid.
(Hyoscia mine.)
the constitution of scopoline must be similar to that of tropine.
Accepting Merling's formula for tropine, Eykman proposed a similar
formula for scopoline.
83
CH2 CH2
/ N /N
/ N / N
HC/ NCH2 HC/ NCH2
N N
CH.OH CH.OH
N N
N N
CH2 CO
N & N
H2ON / CH H2ON / CH
N / N /
N / N /
N.CH3 . N.CH3
Tropine (Merling). Scopoline (Eyknman).
But the researches of Willstätter have shown that tropine has
the following formula
tº. ſh-ºh-ºh,
|
N.CH3 CH.OH
| |
CH2—CH-CH2
Tropine (Willstätter)
hence scopoline cannot have the constitution given to it by Eykman.
This also follows from the fact that all attempts to prove the
presence of a CO group in scopoline were unsuccessful. When scopo-
line was treated with hydroxylamine under various conditions the
alkaloid remained unchanged as was shown by a comparison of
the gold salts. In identifying the scopoline as a chloraurate it was
noticed that the ordinary scopoline chloraurate differed from the
chloraurate obtained from scopoline which had been treated with
hydroxylamine only in the crystalline form and the amount of water
of crystallization they contained. Ordinary scopoline chloraurate
contains half a molecule while the other chloraurate contains One
molecule of water of crystallization. The same chloraurate contain-
ing one molecule of water of crystallization was also obtained from
Scopoline which had been subjected to the action of reducing agents.
But the scopoline hydrochlorides obtained from both chloraurates
were identical in every respect. The chloroplatinate obtained from
scopoline which had passed through the reaction with hydroxylamine
differed from ordinary scopoline chloroplatinate in that the latter
contained two molecules of water of crystallization and crystallized
in transparent reddish-brown crystals, whereas the former crystallized
84
in shining reddish-yellow crystals containing no water of crystalliza-
tion.
In order to avoid the possible influence of the OH group, acetyl-
scopoline was subjected to the action of hydroxylamine, but in this
case too no oxime was formed nor could an oxime be obtained from
methylscopoline or acetyl methylscopoline.
Attempts to obtain a hydrazone of scopoline were also unsuccess-
ful. On heating scopoline with phenylhydrazine acetate only acetyl-
phenylhydrazine, CH3.0O.NH.N.H.C6H5, was formed. That the scopo-
line does not take any part in this easy transformation of phenyl-
hydrazine into the acetyl compound was shown by the fact that the
same acetyl compound was formed by boiling phenyl hydrazine
acetate alone slightly acidulated with acetic acid.
Scopoline does not react with semicarbazide or amidoguanidine,
nor could the presence of a CO group be shown by reducing the base
with various reducing agents. Even hydriodic acid and zinc dust
which very easily reduce tropinone do not affect scopoline.
An attempt to prove the presence of a CH2. CO-group in scopoline
by condensing it with benzaldehyde gave negative results. Only
acetyl scopoline was formed when the reaction took place in acetic
acid solution. An acetyl compound (instead of a nitro derivative)
was also formed when scopoline was treated with amylnitrite in
acetic acid solution.
A crystalline methyl scopoline, Cs H12(CH3) NO2, was obtained by
means of exhaustive methylation of scopoline.
When scopoligenine is subjected to destructive distillation with
zinc dust in an atmosphere of hydrogen the products seem to be the
same as are obtained under the same conditions from tropigenine,
namely, pyridine and unsaturated combustible gases.
Bromine in chloroformic solution converts scopoline into scopoline
hydrobromide, C8H13NO2. HBr.
On exposing scopoline to the action of bromine vapors it is con-
verted into a mixture of the perbromides of the hydrobromides of
Scopoline and scopoligenine. The per-bromine was removed by warm-
ing with water and alcohol and the scopoline hydrobromide separated
from Seopoligenine hydrobromide by the fractional crystallization of
the corresponding chloraurates,
85
When scopoline is heated with bromine and water under pressure
to about 100° again the perbromides of scopoline hydrobromide and
scopoligenine hydrobromide are obtained together with a brominated
scopoline. After removal of the perbromide the brominated com-
pound was separated from the hydrobromides of scopoline and
scopoligenine by means of ether.
Hydriodic acid of the specific gravity 1.7 does not affect scopoline
at 150–160°, but an acid having the specific gravity 1.9 when
heated with scopoline to 190—200° in presence of amorphous phos-
phorus, converts the base into methylamine, hydroscopolidine,
Cs H15N, and some hydrocarbons having the odor of petroleum. The
hydroscopolidine is volatile, has a strong narcotic odor and forms
a chloraurate and a chloroplatinate. Hydroscopolidine is isomeric
but not identical with hydrotropidine.
On heating scopoline with strong hydrobromic acid to 130°
hydrobromscopoline hydrobromide, CsPI14 Brno 2.HBr, was obtained.
When reduced with zinc and sulphuric acid the hydrobromscopoline
hydrobromide is converted into hydroscopoline hydrobromide,
Cs H15NO2.HBr. As was shown by the formation of diacetyl and
dibenzoyl compounds both hydrobromscopoline and hydroscopoline
obtained from it by reduction contain two OH groups and as there
is only one such group in scopoline it must be assumed that there
=(\
is in scopoline the grouping | >O which by the action of hydro-
={}^ –0.O H
bromic acid is converted into the grouping
=0.Br.
An attempt to obtain hydroscopolidine in larger quantities by
eliminating the two OH groups from hydrobromscopolidine by heat-
ing the latter with hydrochloric acid (5%) to 190° was not success-
ful. Under these conditions scopoline was regenerated, but on treat-
ing the hydrobromscopoline hydrobromide with phosphorus tri-
bromide in order to replace the OH groups by bromine and then
reducing the tribromide formed with zinc and sulphuric acid hydro-
scopolidine was obtained but again only in small amounts.
On digesting a strong solution of scopoline with hydrogen per-
oxide the base was transformed into a not very stable oxide,
Cs H13NO3. The oxide liberates iodine from potassium iodide and
86
oxidizes SO2 to SO3 with the regeneration of scopoline. A hydro
chloride of scopoline oxide was obtained by spontaneous evaporation
of a solution of the oxide in dilute hydrochloric acid. When the
hydrochloride of scopoline oxide is treated with gold chloride, oxygen
is liberated and scopoline chloraurate is formed.
The scopoline oxide most probably contains the group =Nzº
On oxidizing scopoline with chromic acid carbon dioxide and
methylamine were evolved and the reaction product gave upon the
addition of gold chloride a mixture of the chloraurates of scopoli-
genine and pyridine methylchloride C5H5N.CH3Cl. This would seem
to indicate that both oxygen atoms of Scopoline are not in the
pyridine nucleus of the molecule. (Arch. Pharm., 1905, 559.)
Solanine.
G. Oddo and A. Colombano have undertaken an investigation
of solanine obtained from Solanum sodomaeum. It seems that
different solanum plants yield different solanines. It is also possible
that even one and the same solanum plant contains different
solanines at different stages of its growth.
The method used for the extraction of the alkaloid from Solanum
sodomaeum was as follows: The drug was digested for five months
with alcohol (91%), the liquid filtered, the alcohol distilled off, the
residue taken up with dilute acetic acid and the alkaloid precipitated
with lime water. The precipitate was boiled with alcohol (not
stronger than 80%) and then a current of carbon dioxide passed
into the liquid. On cooling Solanine separates out in thin white
needles which become brown at 230° and melt with decomposition
at 245 — 250°. The formula of solanine was found to be
(C23H39NOs)2.H2(). The alkaloid is very difficultly soluble in ab-
solute alcoliol but is soluble in aqueous alcohol. From a hot solution
in 91% alcohol solanine separates out on cooling in gelatinous form ;
from alcohol containing not more than 80% it separates out in
crystals. It is easily soluble in dilute acetic acid but very difficultly
soluble in glacial acetic acid, ether, ligroin or acetone. From acetone
solutions the alkaloid separates out in crystalline form. The alka-
loid is also soluble in methyl alcohol but upon recrystallization from
this solvent it seems, to undergo some change as it then melts at
275–280°. $.
87
Concentrated sulphuric acid colors solanine yellow; the color
soon changes to red-violet and then to brown. The solanine
recrystallized from methyl alcohol gives the same color reaction but
with greater intensity.
A solution of solanine in concentrated nitric acid is at first
colorless but soon becomes yellow. In hydrochloric acid solanine
dissolves without color.
On adding to solanine a warm mixture of alcohol and sulphuric
acid the liquid soon assumes a pale red color (compare C. R. 128,
887).
Most alkaloidal reagents form with solanine colored precipitates.
The most characteristic color reaction of solanine seems to be
that of Missaghi (Gaz. chim. ital. 5, 417). It consists in warming a few
drops of a solanine solution with one or two drops of a solution of
platinum tetrachloride to 65–70°. As the liquid evaporates a red
color is developed which changes first to purple and then to violet.
The color disappears slowly on cooling but reappears on warming.
On evaporating an alcoholic solution of solanine with a few
drops of a solution of potassium-platinum iodide (Pt.I.4 + KI) a
yellow color is developed which soon changes first to red and finally
to violet with green layers.
A hydrochloride of solanine was obtained by dissolving the alka-
loid in absolute alcohol freshly saturated with dry hydrochloric acid
gas and then adding ether. The salt forms white microscopic scales
which darken at 135° but do not melt even at 265°. The alkaloid
forms a chloraurate and a chloroplatinate both of which are soluble
in water.
Solanine evidently contains an NH2 group linked to an aromatic
nucleus since nitrous acid converts it into a diazo compound. The
diazo compound when copulated with 8-naphtol forms a colored
compound which can be used as an indicator as it is colored red by
acids and yellow by alkalies.
Boiling hydrochloric acid (2%) hydrolyzes solanine converting
it into solanidine, C19H23NO, and a sugar which seems to be a
hexose.
Solanidine, crystallizes from aqueous alcohol in nacreous scales
melting at 190–192°. The alcoholic solution of solanidine has a
faintly alkaline reaction. Solanidine forms difficultly soluble salts
and, like solanine, is diazotizable.
88
That the sugar formed in the hydrolysis of solanine is a hexose
was shown by the analysis of the osazone. *
It is of course difficult to explain how solanine having the formula,
(23 H2ONOs, can be converted by hydrolysis into solanidine, C19H29NO
and a hexose, ('GH12O6. Hence the formulas of solanine and solani-
dine cannot be regarded as definitively settled.
(Gaz. chim. ital. 1905, 27.)
By a modification of their previous method (see preceeding para-
graph) G. Oddo and A. Colombano have succeeded in increasing the
yield of Solanine from Solanum Sodomaeum. They have also isolated
an acid from the same plant. Having proved by means of Fehling’s
solution that solanine is not hydrolyzed by very dilute acids they
digested the berries with dilute sulphuric acid (2.5%), precipitated
the alkaloid with alkali and recrystallized it from 80% alcohol.
Different samples of berries obtained from different localities yielded
different amounts of solanine varying from 0.25% to 1%.
Thus obtained solanine forms needle-like crystals whose melting
point depends on the way they are heated. Heated slowly with a
small flame they melt at 245–250°, heated with a high flame they
melt at 27:5—280°. If in the method of extraction acetic acid be
substituted for sulphuric acid the alkaloid is obtained in the form
of a white crystalline powder and melts after the first recrystallization
from alcohol at 27.5–280°.
From the alkaline mother liquors of solanine an acid was obtained
by acidulating the liquid and extracting it with ether. The acid after
one recrystallization melted between 195° to 215° and formed small
yellowish prisms. It dissolves in water to a colorless solution which
is turned green by ferric chloride and blood-red by alkalies.
(Ber. Dtsch. chem. Ges, 1905, 2755.)
J. Wittmann has investigated solanine and the decomposition
products obtained by hydrolyzing it.
Of the different formulas proposed for solanine the author finds
that of Firbas to be most in accord with his own analytical data.
Firbas' formula is ('58 H 93NO 18.9%H2O.
Solanidine was obtained by boiling solanine with ten times its
amount of dilute sulphuric acid (2%) till no more solanidine
separated out on further boiling and then cooling the liquid. The
solanidine sulphate was decomposed by anmonia first in aqueous
suspension and then in alcohoiic solution and recrystallized from hot
89
ether. The solanidine melted at 207° and upon analysis gave results
almost identical with those obtained by Firbas. Hence the formula
of Firbas, C40H81NO2, or C41 Hes.NO2, would seem to be correct.
An attempt to make a molecular weight estimation of solanidine
by the boiling point method using chloroform as solvent did not
give very reliable results owing probably to the impossibility of
regulating the boiling of the chloroform.
It was also found impossible to estimate the molecular weight
of solanidine in a Bleier and Kohn apparatus because solanidine
decomposes before volatilizing even when heated under a pressure of
two m. m.
The filtrate from solanidine sulphate was worked up for sugars
as follows: The excess of sulphuric acid was removed by barium
carbonate and the liquid, after filtering, concentrated to a small
bulk. After standing several weeks a crystalline precipitate separated
out which was identified as rhamnose.
The mother liquor of the rhamnose was treated with alcohol till
no more precipitate was produced by further addition of alcohol, the
precipitate was then dissolved in a little dilute alcohol and converted
into a hydrazone by means of methylphenylhydrazine in alcoholic
solution. As the hydrazone resembled in many points the methyl-
phenylhydrazone obtained from galactose the second sugar formed
in the hydrolysis of solanine would seem to be galactose. The slight
differences between the hydrazones might be accounted for by assum-
ing them to be stereoisomerides.
After removal of the rhamnose and the galactose the excess of
methylphenylhydrazine was removed by boiling the liquid with
benzoic aldehyde. The resulting liquid gave indications of the
presence of other sugars, but these could not be isolated in pure
condition.
No crotonic aldehyde could be found among the products of
hydrolysis of solanine (compare Hilger and Merkens, Ber. Dtsch.
chem. Ges., 1903, 3204). (Monatsh., 1905, 445.)
Giovanni Romeo has extracted Solanine from Solanum Sodomaeum
by the following method: The berries were subjected to a strong
pressure and 3950 c. c. of the extract mixed with S0 grams glacial
acetic acid, 50 c. c. water and 3950 c. c. alcohol (93%). After
standing over night the liquid was filtered off from albuminous and
coloring matter, which settled at the bottom of the vessel, and con-
90
centrated to half the original volume under reduced pressure at a
temperature of 50°. After cooling and filtering the liquid an excess
of ammonia was added, the precipitate, after standing 36 hours, was
collected, washed, and dried with gentle heat. The precipitate was
recrystallized from dilute alcohol. Thus obtained solanine forms
colorless needles, becoming brown at 280° and melting at 286°.
Heated a few degrees above 286° it is decomposed. It is very
hygroscopic and had to be dried for analysis in a current of hydro-
gen. It is very little soluble in cold absolute alcohol, ether, benzene
or water but dissolves readily in acidulated water. In hot alcohol of
93–95% it dissolves readily but the solution gelatinizes on cooling.
In hot alcohol of 50–80% it is very easily soluble and separates
out on cooling in crystalline form. It is laevorotatory and its formula
is either Cagli;7NO13 or Cag|H59NO13.
On boiling solanine for a few minutes with dilute hydrochloric
acid (2%) the liquid becomes turbid from the separation of Solani-
dine hydrochloride and then reduces Fehling’s solution.
The color reactions of solanine from Solanum sodomaeum were
found to be mostly identical with those of solanine from Solanum
tuberosum. (Gazz. chim, ital., 1905, 579.)
Sparteine.
C. Reichard has investigated some color reactions of sparteine.
This alkaloid can be distinguished from coniine and nicotine by the
negative results obtained when it is treated with cobalt nitrate in
the way described under conine (Pharm. Centr.-H., 1905, 313). With
copper Oxychloride sparteine assumes a greenish-blue color only after
standing for about 10 hours.
Sodium picrate colors nicotine reddish-yellow, coniine and sparteine
give a yellow color. Strong sulphuric acid changes the nicotine color
to yellow.
With ammonium persulphate and sodium sulphocyanate the
mixture of each of these three alkaloids with the picrate and sulphuric
acid behaves differently: the sparteine mixture assumes a magnificent
orange-red color, the nicotine mixture is not changed at all and the
coniine mixture assumes only a very light Orange color. The sparteine
color is very stable even after 24 hours.
On adding some strong potassium sulphocyanate solution to a
solution of ferric chloride, evaporating the whole to dryness in a
91
very thin layer and then adding one of the three alkaloids the
following colors can be observed : Sparteine or its sulphate gives a
pretty blue-violet color which sometimes appears as red-violet,
nicotine and coniine give a green color. These colors are very stable.
On evaporating a solution of ferric chloride containing some
ferrous salt and potassium ferrocyanide to dryness and adding to
the residue one of the three alkaloids the following colors can be
observed : nicotine gives a dirty light-green color, coniine gives a
yellowish-green color and sparteine gives a bluish-white color. On
now adding a drop of potassium sulphocyanate solution nicotine
and coniine remain unchanged, sparteine assumes a dark-blue color
which on standing changes to a bronze tint.
A mixture of potassium dichromate and sulphuric acid is colored
by nicotine at first yellowish-red and then green, conine and sparteine
color the mixture green immediately.
Conine and sparteine do not color ammonium molybdate, nico-
time colors it yellowish-green. A mixture of ammonium molybdate
and sulphuric acid is colored by nicotine yellowish-green. On adding
ammonium persulphate the color changes to a magnificent violet-
purple which later changes to intense yellow. Coniine and sparteine
color the above mixture light-blue which is changed by the per-
sulphate to an intense yellow. This yellow color obtained from the
three alkaloids is changed by potassium sulphocyanate to an intense
red-brown which is destroyed by formic aldehyde.
On adding a drop of strong sulphuric acid to some powdered
potassium ethylsulphate and then a drop of nicotine the mass
assumes a yellow color which soon changes to red. Coniine and
sparteine are not colored by this reagent.
(Pharm. Centr.-H., 1905, 386.)
R. Willstätter and W. Marx find that sparteine is not affected by
potassium permanganate in presence of sulphuric acid. Hence the
alkaloid must be a saturated compound. It can be oxidized by
chromic anhydride only in presence of rather strong hot sulphuric
acid. Under these conditions three compounds are obtained from
sparteine: spartyrine, C15H24N2, oxysparteine, C15H23N2O, and a
neutral substance having the formula, C15H24N2O2.
For the preparation of spartyrine a definite amount of chromic
anhydride must be used. Smaller amounts leaves most of the
sparteine unchanged while larger amounts yield mostly oxysparteine.
92
Unlike sparteine, spartyrine is easily affected by potassium per-
manganate showing that in the oxidation the saturated base is
changed into an unsaturated one. It is possible that the reaction
consists in oxidizing an H atom linked to a tertiary C atom to an
OH group which is then split off as H20 with the formation of a
double binding:
>;-- ——) >;-- ——x >C==C3 + H2O
|
H. H. H OH
Syartyrine cannot be distilled without decomposition even in
vacuum. It is not volatile with steam and is more laevorotatory
than sparteine. Acids color spartyrine yellow. It forms a hydro-
chloride containing one molecule of water of crystallization which
is not removed in vacuum but is given off at 105°. It also forms
a crystalline chloroplatinate containing three molecules of water of
crystallization which are given off only at 130°. The chloroplatinate
was recrystallized from hydrochloric acid (25%).
Oxysparteine, C15H24N2O, is isomeric with d- and 1-lupanine and
distills at 209° under a pressure of 12.5 mm. It is laevorotatory.
Potassium permanganate does not affect it and chromic anhydride
affects it only in presence of strong hot sulphuric acid. It does not
react with benzoyl chloride or hydroxylamine in presence of alkali.
Hence it is neither an alcohol, nor an aldehyde, nor a ketone. It is
not a cyclic amide like a pyrrolidone because the basicity of both
amino-groups of sparteine is not diminished by conversion into
oxysparteine. It is probable that oxysparteine is an oxide of the
nature of pinol or cineol.
In the oxidation of sparteine to oxysparteine spartyrine is not
an intermediate product, as the latter cannot be oxidized to oxy-
sparteine.
Oxysparteine forms a chloroplatinate containing two molecules
of water of crystallization which are removed at 130° and a double
mercury salt.
The neutral substance, C15H24N2O4, was separated from sparty-
rine and oxysparteine by removing the bases from alkaline solution
by means of ether. It is a very hygroscopic amorphous powder
containing one molecule of water after being dried over sulphuric
acid. The water is removed at 80°. The neutral substance is easily
93
soluble in water and alcohol but insoluble in acetone, chloroform or
ether. It is not affected by potassium permanganate in presence of
sulphuric acid. It does not color pine wood moistened with hydro-
chloric acid, has a neutral reaction and is not esterifiable. By further
oxidation with chromic acid the neutral substance is converted into
a compound having the formula, C15H22N2O4. The properties of this
compound are similar to those of the neutral substance from which
it is made. It contains half a molecule of water which it loses at
80° and swells up when heated to 94°.
(Ber. Dtsch. chem. Ges., 1905, 1772.
Charles Moureu and Armand Waleur have investigated the action
of methyl iodide on sparteine. When sparteine is digested in the cold
with methyl iodide and methyl alcohol two isomeric iodomethylates
are formed. One, a-sparteine iodomethylate, is much less soluble in
water than the other, named a'-Sparteine iodomethylate. The a-com-
pound has an optical rotation of [a] p = — 22.75° and is identical
with the iodomethylate previously obtained by Bamberger (Ann.
1886, 368). The aſ-compound could not be prepared so far in pure
condition. It is very easily soluble in water and has a much higher
rotation than the a-compound. The maximum rotation obtained
was [a] p = —46.3°.
When sparteine is heated with methyl iodide and methyl alcohol
under pressure to 110° the hydriodides of the two isomeric iodo-
methylates are formed the hydriodic acid coming from the methyl
alcohol which is converted into dimethyl ether, (CH3)2O. The
hydriodide of a-sparteine iodomethylate is less soluble in water and
has a lower specific rotation than the hydriodide of the a”-compound.
(Comptes Rendus, 1905, 140, p. 1601.)
Further work by Charles Moureu and Armand Waleur upon the
isomerism of the iodomethylates of sparteine (preceeding paragraph)
shows that this isomerism must be of a stereochemical nature. As
both hydriodides of the isomeric iodomethylates give off all the
methyl iodide when heated to 232° leaving one and the same
hydriodide of sparteine we must assume that in both iodomethylates
the CH3.1 group is linked to the same nitrogen atom. In the
hydriodides of these iodomethylates the hydriodic acid must also be
linked to one and the same nitrogen atom i. e. to that nitrogen
atom which is not linked to the CH3 I group. This was also shown
by the fact that when sparteine monohydriodide is heated with
94.
methyl iodide the same two hydriodides of the two isomeric iodo-
methylates are obtained which are formed when sparteine is heated
with methyl iodide in presence of methyl alcohol (preceeding para-
graph). As in the sparteine hydriodide one nitrogen atom is linked
to the HJ group the CH3 I group in both iodomethylates must go
to the other nitrogen atom in both cases. *
(Comptes Rendus, 1905, 140, p. 1645.)
The same authors have investigated the action of ethyl iodide
upon sparteine. On digesting ethyl iodide with sparteine in absence
of any solvent sparteine hydriodide is formed, the alkaloid, like in-
organic bases, decomposing the C2H5I into C2H4 and HI. If sparteine
be digested with ethyl iodide in presence of absolute alcohol there is
no reaction in the cold, but if the liquid be heated the following
products are formed : sparteine hydriodide, two isomeric sparteine
iodomethylates, the hydriodides of these iodomethylates and some
ethyl ether.
Unlike methyl iodide, ethyl iodide does not react with sparteine
hydriodide. (Comptes Rendus, 1905, 141, p. 49.)
The same authors (preceeding paragraph) prove that contrary
to the statements of Scholtz and Pawelicki the two nitrogen atoms
in the sparteine molecule have the same function. This is shown as
follows:
1. When sparteine methyl iodide is treated with hydriodic acid
the hydriodide obtained is, not only isomeric, but identical with the
hydriodide obtained by treating sparteine hydriodide with methyl
iodide. If one of the two nitrogen atoms were more basic than the
other the more basic one ought to be linked to the HI group or
the CH3 I group according to which reagent is used first leaving the
less basic nitrogen atom to attach itself to the second reagent.
Hence the above hydriodides ought to be only isomeric but not
identical.
2. On heating the hydriodide of sparteine iodomethylate ob-
tained by treating sparteine first with hydriodic acid and then with
methyl iodide the same sparteine hydriodide is formed as by heating
that hydriodide of sparteine iodomethylate which is obtained by
treating sparteine first with methyl iodide and then with hydriodic
acid. In both cases methyl iodide is given off at about 230° leaving
one and the same sparteine hydriodide.
95
As to the action of methyl iodide and ethyliodide used in
succession but in different order upon sparteine the authors’ results
are as follows: When ethyl iodide is made to act upon Sparteine
iodomethylate there is no reaction whatever up to about 200°. At
that temperature the ethyl iodide breaks up into ethylene and
hydriodic acid and the sparteine iodomethylate, after losing all the
methyl iodide, is converted into sparteine dihydriodide. When
methyl iodide is heated with sparteine iodoethylate no reaction can
be noticed up to 140°.
(Comptes Rendus, 1905, 141, p. 117.)
The same authors have subjected sparteine to exhaustive methyl-
ation and obtained following results: On converting a-sparteine
iodomethylate into methylsparteinium hydroxide and heating the
latter to 175° in vacuum, water is eliminated and methylsparteine,
C15H25N2.0H8, is formed. When this methylsparteine is converted
into methylsparteine methylhydroxide by the successive treatment
with methyl iodide and silver hydroxide and the ammonium base
again heated to 17.5° water is again eliminated and dimethylsparteine,
C15H24N2(CH3)2, is formed. When this base is treated with methyl
iodide and silver hydroxide successively and the dimethylsparteine
methyl hydroxide so obtained again heated to 200–210° the base
is decomposed into H2O, (CH3)3N, and an oily liquid corresponding
to the formula, C15H23N, which was named sparteilene. As sparteine,
methylsparteine and dimethylsparteine are all tertiary bases and no
(CH3)3N is evolved except in the last stage of the exhaustive methyl-
ation when sparteilene is formed we must assume that the nitrogen
atom of sparteine to which the alkyl groups attach themselves is
linked to a bicyclic system. But as previous investigations have
shown sparteine has a symmetrical structure, hence the second
nitrogen atom must also belong to a bicyclic system.
(Comptes Rendus, 1905, 141, p. 261.)
The same authors propose a constitutional formula for sparteine,
The alkaloid has the formula, C15H26N2, is a bitertiary base and is
symmetrically constructed with regard to the two nitrogen atoms.
Hofmann’s method of exhaustive methylation (preceeding paragraph)
showed that both nitrogen atoms belong to a bicyclic system. The
alkaloid scarcely gives the pyrrol rea, 'tion with pine wood and hydro-
chloric acid. The formula that would best explain these facts is the
following:
96
CH CH
/ N /N
/ | N / | N
H2O/ | NCH2 H2O/ | N(SH2
CH2 (JH2
CH2 | CH2
H2CN | /CH –CH2 — HCN | /CH2
N | Z N | Z
N /
N N
That the CH2 group which links the two rings together is in the
Ortho position to the nitrogen atoms is shown by the fact that
sparteine gives two stereoisomeric iodomethylates when treated with
methyl iodide. As according to Scholtz (Ber. Dtsch. chem. Ges.,
1904, 3627) only those bases which, like coniine, contain the
asymmetric carbon atom in the ortho position to the N-atom are
capable of giving such stereoisomers, in sparteine too the asymmetric
carbon atoms must be in the Ortho position to the nitrogen atoms.
(Comptes Rendus, 1905, 141, p. 328.)
Strychnine.
H. Beckurts has investigated the action of broumine on strychnine.
When an excess of bromine water is added to a dilute solution of
strychnine hydrochloride bromstrychnine tribromide, C21H21 Brn 202-
Bra, is precipitated. From solutions of Strychnine nitrate bromine
also precipitates yellow brominated compounds but these contain
less bromine together with considerable amounts of nitric acid.
On warming the bromstrychnine tribromide with alcohol the
additive bromine oxidizes the alcohol to aldehyde (recognized by the
odor) and monobromstrychnine hydrobromide, C2 [H21 BrN2O2. HBr.,
remains in solution. The monobromstrychine can be obtained from
this solution by evaporating the alcohol, taking up the residue with
water and precipitating the base with ammonia. The hydrobromide
of monobromstrychnine can be obtained by adding ether to the
above alcoholic solution. The same monobromstrychnine is formed
on adding the tribromide to alcoholic potassium hydroxide or by
treating the tribromide with sulphuretted hydrogen and, after filt-
ration, precipitating the base with ammonia, or by reducing the
tribromide with nascent hydrogen and then adding ammonia.
97
When the tribromide is heated to 105° it is converted into brom-
strychnine dibromide, C21 H21 N2 BrO2. Brz. The dibromide behaves
like the tribromide towards alcohol and heat.
The tribromide can also be converted into the dibromide by
washing the former with cold alcohol till the liquid comes out only
slightly yellowish. (Arch. Pharm., 1905, 493.)
M. J. Minguin has investigated the variation in optical rotation of
strychnine salts due to the presence of excess of acid. As solvent a
mixture of ethyl and benzyl alcohols (1 + 2) was used. The results
obtained were as follows: With strong acids the rotation of the salts
of strychnine is not influenced by excess of acid; strychnine sulphate,
for example, has the same rotation as a solution of strychnine in
an excess of dilute sulphuric acid. In the case of weak acids the
difference between the rotation of the salt and the rotation of a
solution of the alkaloid in excess of acid is greater the weaker the
acid used. This must be due to partial hydrolysis of the salts.
While the rotation of the salts of strychnine with different acids
varies with the acid the rotation of solutions of strychnine in excess
of acid is practically constant for acids of homologous series. The
presence of double bindings in the acids used also has a great
influence upon the optical rotation of strychnine salts.
(Compt. rend., 1905, 140, 243.)
According to A. Bacovescu and A. Pictet when strychnine is heated
with water to 160–180° it is changed to an isomeric compound,
named isostrychnine, which has the same relation to isostrychninic
acid as strychnine to strychninic acid (strychnol).
CO CO—O II
C20H22NO/ | C20H22NO /
NN N. NH
Strychnine and Isotrychnine. Strychninic Acid and Isostrychninic Acid.
(Dihydrostry ell nine)
Just as strychnine is converted into strychninic acid upon boiling
with a solution of sodium ethylate, in the same way isostrychnine
is changed under these conditions to isostrychninic acid.
Isostrychnine crystallizes from hot water with three molecules of
water of crystallization. It melts both crystalline and anhydrous
at the same temperature (214.5°). It is optically inactive, is quite
soluble in hot water, alcohol and dilute acids, but difficultly soluble
in cold water and insoluble in alkalies. The aqueous solution of
isostrychnine has an alkaline reaction and gradually assumes a
98
brown color particularly in presence of alkali. Isostrychnine is as
bitter as strychnine. With potassium dichromate and sulphuric
acid isostrychnine gives a violet color which soon changes first to
yellow and finally to bluish-green. Strychnine is also colored violet
by the same reagent but the color changes to a permanent yellow.
According to Tafel (Ann., 1892, 233) this color reaction is characteristic
of many anilides and depends upon the presence of the group .CO.N:
Bromine water gives a bright yellow precipitate in aqueous solu-
tions of isostrychnine the liquid remaining colorless. Under the same
conditions isostrychninic acid solutions are colored purple-red. Ferric
chloride does not color solutions of isostrychnine in the cold but on
warming the liquid becomes red. A solution of isostrychnine in
sulphuric acid is not affected by nitric acid (strychninic and iso-
strychninic acids give under the same conditions a red color.) Man-
delin's reagent colors isostrychnine blue-violet (same as strychnine)
which gradually changes to light brown (in the case of strychnine
the color changes to orange-red). The salts of gold, platinum and
silver are reduced by isostrychnine.
The salts of isostrychnine are more soluble in water and have
less tendency to crystallize than the salts of Strychnine. On boiling
isostrychnine with alkalies it is changed to a brownish pitch and an
oily base which is volatile with steam and has the odor of quinoline.
Isostrychnine is much less poisonous than Strychnine.
(Ber. Dtsch. chem. Ges., 1905, 2787.)
On oxidizing strychnine with hydrogen peroxide A. Pictet and M.
Mattisson have obtained strychnine oxide, C21H22N2O3.3H2O. As
there is only one basic nitrogen atom in strychnine and the nitrogen
atom of the group : N.C.O.R is not capable of combining with oxygen
(Ber. Dtsch. chem. Ges., 1899, 2507) the formula of strychnine
Oxide must be
CO
| >(C28H22O);N30
| 20 20 IT 22 U') : IN .
Nº
Strychnine oxide melts at 199° with evolution of vapors which
color pine wood intensely red. The oxide dissolves readily in water
to a solution having an intensely bitter taste and a neutral reaction.
It has a specific rotation of –1.75° and gives the color reactions of
Strychnine. Its solution is not affected by ferric chloride in the cold
but on warming a red color appears. It loses oxygen very easily
99
changing back to strychnine. It liberates iodine from potassium
iodide and is reduced by SO2 to strychnine sulphate. The amount
of oxide oxygen can be estimated by treating the oxide with SO2
and BaCl2.
On treating the oxide with sodium nitrite in acid solution
strychnine is regenerated without formation of a nitro derivative.
As according to Bamberger and Tschirner dimethylaniline oxide
under these conditions gives nitro compounds, the basic nitrogen
atom of strychnine seems not to be linked directly to a benzol ring.
The oxide is a weak monoacid base forming salts that are diffi-
cultly soluble in water and contain no water of crystallization.
Sulphurous anhydride reduces the salts to the corresponding
strychnine salts. Unlike strychnine, Strychnine oxide is not pre-
cipitated from the solution of its salts by ammonia.
Like other amino-oxides strychnine oxide does not form an iodo-
methylate. When the oxide is heated with methyl iodide to 100°
strychnine iodomethylate is formed.
Strychnine oxide is considerably less toxic than strychnine.
From the formation of strychnine oxide the same conclusion can
be drawn with regard to the constitution of strychnine as was drawn
by Freund in the case of cevine (Ber. Dtsch. chem. Ges., 1904, 1946).
As only such tertiary bases form aminooxides in which the nitrogen
atom is linked to three different carbon atoms and as there is no
alkyl group linked to the basic nitrogen atom of strychnine this
nitrogen atom must belong to two ring systems.
Brucine also seems to form an aminooxide when treated with
hydrogen peroxide. (Ber. Dtsch. chem. Ges., 1905, 2782).
Berthelot and Gaudechon have made some thermochemical
determinations of strychnine and brucine.
Stry ch nine. — Freshly precipitated strychnine is hydrated and
in its transformation to the anhydrous condition about three calories
are evolved. Crystalline Strychnine hydrochloride contains one and
a half molecules of water of crystallization which it loses at 120°.
Neutral strychnine sulphate forms a dihydrate and a hexahydrate
but is not known in anhydrous condition. The acid sulphate exists
either anhydrous or as a dihydrate. The heats of formation and of
solution of these salts were also determined. Strychnine acetate
contains one and a half molecules of water of crystallization and
does not completely dissolve in Water unless excess of acid be present,
I 00
Bru cine.—Carefully prepared brucine corresponds to the formula,
C28H26N2O4. On bringing anhydrous brucine in contact with water
considerable heat is evolved. When precipitated by ammonia from
a solution of its salts the alkaloid contains four molecules of water
of crystallization of which two are given off in the air at ordinary
temperature and the remainder is removed at 110° or in vacuum
over sulphuric acid. Brucine is monoacid but is soluble only in
excess of dilute acids. When brucine is recrystallized from aqueous
alcohol the alkaloid contains one molecule of alcohol and two mole-
cules of water of crystallization. Crystalline brucine hydrochloride
contains four molecules of water of crystallization of which three are
given off in the air at ordinary temperature and the fourth at 130°.
Anhydrous brucine absorbs more than four molecules of hydrochloric
acid with evolution of heat.
Strychnine sulphate contains six molecules of water of crystal-
lization which cannot be removed by heat without decomposition.
(Compt. rend., 1905, 140, 753.)
Tarconine.
In an investigation on tareonine and its relation to cotarnine
and hydrocotarnine D. Bruns shows that while the difference between
tarconine methyl iodide and cotarnine iodide, both being salts of
ammonium bases, consists only in the number of double bindings, of
which the former has one more than the latter, there is a radical
difference between the free bases which consists in the following:
CH3. O
CH3. () / CH3
/N/N (H3 o/N/ Nº
O N.< , , , / | I
(Hoº |[' l CH2S | | -
ºr 2N ON \ ^CH2
"N/ \ / N/ N /
N CH2
Tarconine methyl iodide. CO tarnine iodide.
(I) - (II)
When cotarnine is liberated from its salts it takes up One mole-
cule of water and changes to a pseudoammonium base (II) to (III)
assuming the aldehyde formula. On the other hand free tarconine
is not a pseudo base having an aldehyde or ammonium hydroxide
formula, but has formula (IV).
101
CH2.0H2.N.H.CH3
Cotturnine
(III)
º º *
ºv/\/
Tarconine
(IV)
Hence the tendency to form pseudo bases does not seem to be
very great.
It is also shown that the chromophore group in berberine and
some other yellow compounds related to it is not the double binding
between the nitrogen and a carbon atom but the double binding
between two particular carbon atoms. This is shown as follows:
O.CH3
cº /
| Z
N/\!/
`
|N
O
/
|
N /
N/
/CH2
CH2
/
NO
|
N
| N/
| CH2
I
Berl)erine iodide
(yell
ow)
(V)
CH2
N /
CH2
Dihydrob
erberine
(yellow)
(VI)
102
Berberine iodide contains one double binding more than dihydro-
berberine and two double bindings more than tetrahydroberberine
(canadine).
| CH3. O
CHR.O CH |
y N A N 2 ^ / O /NN.ch,
choſ N / Yºh º CH2( |
| | Nº O CH2.
N J. /N /CH2 N/ Y.
N / N / N / 2
CH2 CH2
Tetrahydroberberine (canadine) Hydrocotarnine
(colorless) (colorless)
(VII) (VIII)

As both berberine iodide and dihydroberberine are yellow whereas
tetrahydroberberine is colorless the chromophore group must be that
particular double binding between two carbon atoms which is absent
from tetrahydroberberine, not the double binding between nitrogen
and carbon which is also absent from dihydroberberine. A similar
relation exists between tarconine methyl iodide (I), cotarnine iodide
(II) and hydrocotarnine (VIII). Tarconine methyl iodide is yellow
but cotarnine iodide containing one double binding between two
carbon atoms less than tarconine methyl iodide though still contain-
ing the double binding between nitrogen and carbon is colorless.
Hydrocotarnine having lost both these double bindings is also color-
less.
The tarconine methyl iodide (I) was prepared by oxidizing nar-
cotine with iodine in alcoholic solution (Roser's method). For this
purpose the alcoholic solution of narcotine was boiled with iodine
for ten hours and the periodides which separated out on cooling
were reduced by SO2 or H2S (The opianic acid formed in the reaction
remains in the alcoholic solution). The iodides were then extracted
with boiling water and the tarconine methyl iodide separated from
the iodotarconine methyl iodide formed in the reaction by slowly
warming the mixture of the two with water. At a certain tempera-
ture the crystalline mixture separates into the easily soluble tar-
comine methyl iodide which remains in the liquid and the difficultly
103
soluble iodotarconine methyl iodide which separates out as a fine
yellow powder and is quickly filtered off.
The cotarnine (III) was prepared by warming narcotine with
dilute nitric acid till no more teropiammone separated out, the
cotarnine then precipitated by potassium hydroxide and recrystallized
from benzene.
The hydrocotarnine (VIII) was prepared by reducing either
cotarnine or tarconine methyl iodide with zinc and sulphuric acid.
The hydrocotarnine was identified by its melting point and by con-
verting it into its hydrobromide.
On oxidizing hydrocotarnine with iodine either cotarnine or tar-
conine methyl iodide can be obtained according to the amount of
iodine used. As shown by titration of the excess of iodine the
formation of tarconine methyl iodide is quantitative when excess of
iodine is used.
When cotarnine is oxidized with iodine it is only partly converted
into tarconine methyl iodide.
Attempts to bring tarconine methyl iodide into reaction with
acetone, chloroform, or ammonium sulphide were not successful.
When tarconine is set free from its sulphate by barium hydroxide
and the liquid shaken out with ether a compound goes into the
ethereal solution which from its solubility in ether might be assumed
to be the pseudoammonium base, methyltarconium hydroxide.
CH3 O * {"H 3, () ("HO
o/N/NN." o/N /
CH3( | OH CH2(
| |
"N/N/ ov º
Methyltarconium hydroxyde Methyltarconiumhydroxide
(Annonium base), (Aldehyde form).
But on evaporating the ethereal solution the residue was oily
and insoluble in dilute sulphuric acid showing some deep decom-
position. That the compound was not an aldehyde was shown by
the impossibility of bringing it into reaction either with free
hydroxylamine in ethereal solution or with hydroxylamine hydro-
chloride in absolute alcohol. (Arch. Pharm., 1905, 57.)
104.
Thebaine.
On reducing codeinone with stannous chloride L. Knorr obtained
the same thebainone which was obtained by Pschorr by reducing
thebaine under the same conditions. Thebainone is isomeric with
codeine and is formed according to following equation:
C18H19NO3 + H2 —— (318 H21NO3
Codeinone. r Thebain One.
Hence thebainone can be called dihydrocodeinone.
(Ber. Dtsch. chem. Ges., 1905, 3171.)
M. Freund continues his investigations on thebaine and the con-
stitution of morphine and codeine.
As a result of previous experiments it had been supposed that
morphine and codeine are derivatives of a tetrahydrophenanthrene
and thebaine a derivative of a dihydrophenanthrene. Owing to the
formation of thebaol and oxethylmethylamine, H.O.C2H4, NH, CH3,
N
|
|
/
Theł) a,Ol.
from thebaine under certain conditions it was supposed that of the
three oxygen atoms of thebaine two were in the form of CH3.O
groups and the third belonged to an oxazine ring. The formula of
thebaine was therefore supposed to be
CH3. O O—CH2
3 \chi^ \ch.
CHA.O/ \N(CH3)2
As the researches of Wongerichten, Pschorr and Knorr have
thrown some doubts about the correctness of this way of represent-
ing the linking of the “indifferent” oxygen atom the author studied
105
the effect of Grignard's reaction upon thebaine and found that the
alkaloid is converted by magnesium phenylbromide into a compound
of the formula, C25H27NO2, which was named phenyldihydrothebaine.
That the “indifferent” oxygen atom takes part in this reaction is
shown by the properties of the new base which besides two CH30
groups contains an OH group and therefore forms salts both with
acids and bases. The facility with which the “indifferent” oxygen
atom reacts with Grignard’s reagent might suggest the supposition
that this oxygen atom belongs to a CO group, but as thebaine does
not react with hydroxylamine or phenylhydrazine it must be sup-
posed that the oxygen atom is present in the form of a ring which
opens up in Grignard’s reaction in the same way as, for example,
ethylene oxide.
The absence of an oxazine ring in thebaine cannot definitively
be shown by the formation of a phenolic compound in the reaction
of this alkaloid with Grignard’s reagent because even in the presence
of an oxazine ring we could explain the formation of a phenolic OH
group by assuming that in the reaction the ring opens up according
to following scheme e
CH3. O O—CH2 CH3. O OH
\chi^ \ch 2—) >eº
CHs.o/ NN(CHA) / CH.802° N(CH3). CH2.0H2.06H5
That such an interpretation of the reaction is nevertheless not
correct is shown by the results obtained in the exhaustive methyl-
ation of phenyldihydrothebaine. When this phenyldihydrothebaine
is converted into the quaternary iodomethylate and the latter
treated with alkali, the nitrogen is not eliminated in the form of
(CH3)2N.CH2.0H2.Califi as ought to be the case if the above inter-
pretation of the reaction with Grignard's reagent were correct, but in-
stead a new compound is formed which has the formula, C26H29NO3,
and is a tertiary base showing that the nitrogen atom is not split
off at all. When this new compound, named des-N-methyl-phenyl-
dihydrothebaine, is converted into its iodomethylate and the latter
decomposed with alkali, trimethylamine is split off and a nitrogen-
free substance is formed which has not the formula, C24H22O3, but
contains CH2 less having the formula, C28H2008. It was named
phenyldihydrothebenol. *
. These reactions not being in accord with the assumption of an
106
oxazine ring in thebaine the author proposes the following new
constitutional formula for this alkaloid
CH
/ N
CH3O.CZ 2 NCH
| 8 1
4.
(3/N /NC
/ CN / NCH
of ...
N |CH CH
N / N z'
H20–CN / N/ CH
5
6
CH30.0N / CH
N /
CH
H2C==–N.CH3
Thebaine.
(I)
Thebénine, thebenol and pyrene all of which are formed under
&eſtāīā conditions from thebaine would have to be given the followińg
formulae: cHo / CH.0/ N
“ſ | n
‘. novº º 0.


ÖH3.NB.CH2.0H2 /
O
Thébenine. Theben Ol. Pyrené.
(II) (III) (IV)
The conversion of thebaine into theoenine consists then in the
conversion of the “indifferent” oxygen atom of thebaine into an
OH group, the separation of the nitrogen “bridge” and the saponifi-
cation of the CH3 O group in 6. In the conversion of thebénine into
thebenol by exhaustive methylation the nitrogen is eliminated and
the group — CH2 — CH2 — together with the O of the OH group in
6 form a new reduced furfurane ring. That it is the O of the OH in
107
6 that furnishes the O of the furfurane ring is shown by the decom-
position of phenyldipydrothebaine. The formation of this compound
can be represented by the following scheme:
º º
/* N 4. Brºos, /\
/
lch
OS ch –). C6H5 |CH –)
N / N / N /N /
CH2 NZ NZCH CH2 N N/CH
2 * **------> -º.
|
|8
CH3.ON 4 /|CH CH3. ON / CH
Nº. N/
CH CH
CH2=====N.CH3 CH2—N.GHs
Thebaine.
CH3. ". ^
1. |
on /\
|ch
C6H5 |CH
N /N /
CH2 N/ N/CH
|2
cho", "ch
3.
CEH
CH2 N.CHs
Phenyldihydrothebaine.
(V)
As the group which takes part in this reaction seems to be that
part of the thebaine molecule which is made up of the group,
^-
i 2 3 4.
C—O—C–C–CH
&ch,
it is possible that (as is frequently the case with a system of eon-
jugated double bindings) Grignard's reagent adds itself in 1,4 with
the displacement of a double binding. Hence phenyldihydrothebaine
might also have the following constitution
(H2 C/ N /
CH2 N.CH3
Phenyldihydrothebaine.
(VI)
Unlike thebaine, phenyldihydrothebaine is very stable towards
acids. Even hot concentrated hydrochloric acid which converts the-
baine into morphothebaine produces no other change in phenyl-
dihydrothebaine than the elimination of the methyl groups from the
two CH3O groups with the formation of nor-phenyldihydrothebaine
(VII)
Hoº Hoº
| |
|
Ho /> * Ho-Jº
|ch
C6H5 |CH Or ch |
N / N / /N /
CH2 sº N/CH • CH2 C/ N/CH
| |
HO /|CH HON /|CH
N/ 'N /
- CH C6H5.0H p
H2 N.CH3 * CH2— N.CH3 , ,
(VII)
Acetic anhydride causes no other change in phenyldihydro-
thebaine than converting it into the corresponding acetyl derivative.
The formation of des-N-methylphenyldihydrothebaine (VIII) and
phenyldihydrothebenol (IX) in the exhaustive methylation of phenyl-
dihydrothebaine can be represented by the following scheme (taking
WI, for example): * , 4 -
——)
CH2 / N/CH
|
CH3. ON A CH
N /
C6H5.0H
H2 - N.CH3
Phenyldihydrothebaine.
cho, N *- ch, o/ N
|
|
d i |
HON / N HON / N
N N - N/ N
| ; | |
|CH | ——) |CH
/N / N
CH2.0H2 / N / H2C / N /
| C |-
i
N(CH3)2 /N /CII H2CN / N / CH
/ N / N / N /
CH3O (XH.C6H5 J O CH.C6H5
Des-N-methylphenyldihydrothebaine. Phenyldihydrothebenol.
(VIII) (IX)a.
The phenyldihydrothebenol might also have the following formula:
\/\
|c
/ 2. '
H2C / N/
{ | | ||
H2CN Z N *H,
N / N/
O CH.C6Hs
Phenyldihydrothebenol.
! (IX)b
110
In the conversion of des-N-methylphenyldihydrothebaine into
phenyldihydrothebenol by exhaustive methylation, trimethylamine
is split off, the CH3 of the CH3O group in 6 is eliminated and the
furfurane ring is closed. This closing of the furfurane ring seems to
take place with great facility, the same phenyldihydrothebenol being
formed even when the splitting up of the quaternary iodomethylate
of des-N-methylphenyldihydrothebaine is effected by means of sodium
ethylate. That it is the O atom of the CH3O group in 6 that serves
to form the furfurane ring in the thebenols, not the O of the OH in
4 is shown by the following facts. When in phenyldihydrothebaine
(WI) the OH in 4 is methylated and the resulting methyl ether sub-
jected to exhaustive methylation two isomeric compounds are formed
having the formula C24H22O3 and containing two CH3O groups. The
compounds were named a- and -3-phenyldihydrothebenol methyl
ether (X) and (XI)
º N * chlorº
*
(JHS.ON N CH3.ON /N
*. sy/ N N / N
|ch |
|CH |C
/ N / / /
H2C / N / H20 / N/
|
|
H2ON / N / CH H2ON /N / CH2
N / N / N / SS /
O CH.C6H5 O CH.C6H5
Q-Phenyldihydrothebenol methyl ether. (3-Phenyldihadrothebenolmethyl ether.
(X) (XI)
If instead of the methyl the ethyl group be introduced into the
OH group of phenyldihydrothebaine (VI) and the resulting ethyl
ether be subjected to exhaustive methylation a compound is formed
which has the formula C25H24Os and contains one CH3O and one
C2H5O group. It was named phenyldihydrothebenol ethyl ether (XII).
Hence the oxygen atom of the furfurane ring does not come from
the OH in 4 in phenyldihydrotoebaine (VI).
.#41
H2CN /"N 2°CH
N / N/
O CH.Co Hs
Phenyſäihydrothebenolethyl ether.
(XII)
The phenyldihydrothebaine (VI) is a derivative of dihydrothe-
baine which had been previously prepared from thebaine by means
of sodium and alcohol. This dihydrothebaine contains an OH group
and when the latter is methylated and the resulting ether subjected
to exhaustive methylation the same series of reactions takes place
as in the case of phenyldihydrothebaine except that the final nitrogen-
free product is not phenyldihydrothebenol (IV) but methylthebaol
(XVI). The two carbón atoms of .CH2.0H.N(CH3) group which in
the case of the phenyl base serve to form the furfurane ring are in
the case of dihydrothebaine eliminated, most probably as ethylene.
The reactions by which thebaine is converted into methylthebaol
can be represented as follows:
/ N /N
CH3. O/ N CHs.O/ N
| i |
| | |
/ N N HON Ž N
/ s/ N N/ N
of | | |
N (CH || 2H |
* N /N Z ——). * / N A X
CH2 CN / N / CH CH2 HC/ N / CH
| | t
| *
CHå Ö / CH CHs.O /|CH
cºov N/
CH3—N.CHà CH2— —N.CHà
Thébaïe. Dihydrothébâlne.

(xīrī)
112
º
|
(Hºo-yº
| |
|CH
/ N /
ºn-cºne- N/C
| |
N(CH3)2 CH3.0 / CH
N /
Methyl ether of des-N-methyl
ca.o.º.
CH3.ON /N
N / N
|
——) |CH |
/N /
CH2 = CH.HC/ N/C
CH3. ON / CH
g N /
Vinyldihydromethyltheba.ol.
dihydrothebaine. (XV)
(IV)
A N ". . .
CHs.O. º,
ºf
3. *
s/ N CH2
ſº | | + |
/ / CH2
zºNº
CH º 2
sos Z
Methylthebaol.
(3.4.6-Methoxyphenanlhrene).
(xVI)
The reason why in the dihydrothebaine reactions the side chain
..CH2:CH. is split off whereas in the phenyldihydrothebaine reactions
the side chain goes to form a furfurane ring is possibly in the
different position of a double binding in the , benzol ring to which
this side chain is attached (compare VIII and XIV).
The previously observed conversion of thebaine into acetylthebaol
and methyloxethylamine by means of acetic anhydride can also be
explained by the new formula of thebaine.
113
* ^
| |
2^^

OQ ch |
N / N /
CH2 N / N /
|
|
CH3. O /|CH
N /
CH2 N.CH3
Thebaine.
+ H3O =
*/ N
HO N
| + HO.CH2.CH2.N.H.CH3
/N
Oxethylmethylamine.
º
Theba Ol.
-
The formation of morphothebaine from thebaine by "the action
of hydrochloric acid can be explained by assuming that only one
end of the nitrogen “bridge” is detached in this reaction forming a
chloride which then loses hydrochloric acid and is converted into
morphothebaine.
/
choºl CH3. O/ N
! | HO'N / N
N N
y^ sº N | |
©. | |
OQ |ch HCl, /N Z ——x
/N / / N /
CH2 Y N/CH |CH
| |
| © HO /CH
cº-ovºn N/ N
/ CH N.CH3
CH /
CH2 N.CH3 Cl.0H2.0H2
Thebaine. Chloride of Morphothebaine.
Morphothebaine might therefore have either of the following
formulas:
114
| /N
CHs.oz. N
|
| - y */ |
- ^ſºn.
HoN ANCH |
|
ëſ inch Ho ^ch ºch
IN.U II 3 2
| N/ N/
H2O CH2 N.CH3
Morphothebaine. Morphothebaine.
It is possible that the acid chloride obtained by Howard by the
action of hydrochloric acid upon thebaine was the hydrochloride of
the chloride of morphothebaine.
According to the new formula of thebaine the latter is not a
derivative of a dihydrophenanthrene as previously supposed but of
a tetrahydrophenanthrene. Morphine and codeine would then be
derivatives of a hexahydrophenanthrene. As Knorr’s researches have
shown, codeine can be converted into thebenine and morphothebaine,
hence morphine, codeine and thebaine must all have the same con-
stitutional formulas and the greater stability of the first two towards
acids and alkalies can be ascribed only to the different degree of
reduction of the phenanthrene nucleus.
^
CH3. O/ /
cº N
/N /> © | |
/ N / N ^^
o6. | | / N N
N |CH ) o6. | |
N / N / N |CH X
CH3 N / N / N /N /
| CH N/ N/
| CH2 CH2
HO. HCN /|CH
N / N HO. HCN /CH
CH2 | N /
CH2—N.CH a (CH3)2 CH2
Codeine, - Methylmorphimethine.
115
/ N
CH3O/ N.
|
/ N N
/ N / N
2 |
OS |CH |
N / N /
N / N /
H20: HC |
HC's Zoh
\/
CH
Intermediate product.

cho.'N choºl
| |
/Nº º
o( || || — | |
Nº * º
Ny/ N/
Morphenol methyl ether. Methylmorphol.
The conversion of codeine into morphenolmethyl ether and
methylmorphal by exhaustive methylation (Wongerichten, Ber. Dtsch.
chem. Ges., 1900, 352) corresponds to the conversion of dihydro-
thebaine into methylthebaol described above.
The new compounds mentioned in this article were prepared as
follows: The phenyldihydrothebaine (VI) was obtained by adding
powdered thebaine to a solution of brombenzol and magnesium in
absolute ether. The precipitate formed was dissolved in dilute acetic
acid, converted into the hydrio lide by means of potassium iodide
and the hydriodide recrystallized from alcohol On adding ammonium
chloride to a solution of the hydriodide in sodium hydroxide the
free phenyldihydrothebaine separated out.
A sodium salt of the phenylbase was prepared by adding strong
sodium hydroxide to the aleoholic solution of the base. The phenyl
base is very stable towards alkali with which it can be boiled with-
out decomposition. Sodium alcoholate also does not affect it.
116
The iodomethylate of phenyldihydrothebaine was made by digest-
ing the base in alcoholic solution with methyl iodide.
The des-N-methylphenyldihydrothebaine (VIII) was prepared by
boiling the iodomethylate with potassium hydroxide (30%), pour-
ing off the excess of alkali, dissolving the oily residue in water and
precipitating the des-base with ammonium chloride. The des-base is
soluble in most Organic solvents and has no sharp melting point
beginning to melt at 55° and becoming liquid only at 90°. The
des-base can also be prepared by boiling phenyldihydrothebaine
iodomethylate with a hot-saturated solution of sodium ethylate and
precipitating the base with ammonium chloride.
The phenyldihydrothebenol (IX) was obtained by digesting the
iodomethylate of the des-base with a strong solution of sodium in
absolute alcohol. When the evolution of trimethylamine had ceased
the liquid was diluted with water, the alcohol evaporated and the
plmenyldihydrothebenol, after adding ammonium chloride, shaken out
with ether. The compound can be recrystallized from alcohol or
glacial acetic acid. It forms an addition product with bromine when
treated with it in chloroformic solution. The thebenol forms a
sodium salt when treated with strong sodium hydroxide but the salt
is dissociated by water.
The methyl ether of phenyldihydrothebaine was made by digest-
ing molecular quantities of phenyldihydrothebaine, sodium ethylate
and the methyl ester of para-toluol sulphonic acid in alcoholic solu-
tion. It was purified by solution in acetic acid and precipitation
with sodium hydroxide. The ether begins to melt at 60° and be-
comes liquid at 70°. Methyl iodide converts the ether into its iodo-
methylate. The same iodomethylate can be obtained by treating
phenyldihydrothebaine with an excess of methyl iodide in the presence
of sodium ethylate.
The des-N-methylphenyldihydrothebaine methyl ether was pre-
pared by heating the iodomethylate of phenyldihydrothebaine methyl
ether with sodium ethylate, evaporating the alcohol and, after dilu-
tion with water, shaking out the des-base with ether. It was
analyzed as a platinum salt. The des-N-methylphenyldihydrothebaine
methyl ether reacts violently with methyl iodide forming an iodo-
methylate which, when heated with sodium ethylate, is converted
into a-phenyldihydrothebenol methyl ether (X). The same compound
can be obtained by treating phenyldihydrothebenol (IX) with methyl
117
iodide and sodium ethylate. When heated above its melting point,
or boiled for some time with amyl alcohol, or heated with acetic
anhydride and sodium acetate to 100° the a-compound is transformed
into the 8-modification (XI). Both the 4- and -3-compounds are
optically inactive and combine with sodium ethylate to form crystal-
line addition products which are decomposed by water. The isomers
differ from each other in melting point: the q-compound melts at
114–115°, the 3-compound melts at 124°.
On digesting phenyldihydrothebaine with ethyl iodide and sodium
ethylate the OH is etherified but no iodoethylate is formed even in
the presence of an excess of ethyl iodide. When the ethyl ether of
phenyldihydrothebaine is boiled with methyl iodide in alcoholic solu-
tion the iodomethylate of the ether is formed which is converted by
boiling with sodium ethylate into des-N-methylphenyldihydrothebaine
ethyl ether. This des-base by treatment with methyl iodide was
converted into the corresponding iodo methylate and the latter by
digestion with sodium ethylate into phenyldihydrothebenol ethyl
ether (XII). The same ethyl ether was obtained by warming phenyl-
dihydrothebenol (IX) with ethyl iodide and sodium ethylate.
An acetyl derivative of phenyldihydrothebaine was prepared by
heating the latter (VI) with acetic anhydride and sodium acetate
and precipitating the base with sodium hydroxide. The acetyl com-
pound is soluble in warm methyl iodide and on cooling the iodo
methylate of the acetyl base separates out in crystals.
The nor-phenyldihydrothebaine (VII) was made by boiling the
hydriodide of phenyldihydrothebaine with strong hydriodic acid.
The same nor-compound can be obtained by heating phenyldihydro-
thebaine with hydrochloric acid (1.19) to 100° in closed vessels.
The nor-base forms crystalline salts with sulphuric and acetic acids.
It is soluble in sodium hydroxide with the evolution of the odor of
benzaldehyde.
On boiling the iodomethylate of dihydrothebaine methyl ether
with potassium hydroxide (30%) till the substance becomes com-
pletely soluble in ether it is converted into des-N-methyldihydro-
thebaine. By means of methyl iodide the des-base was converted
into its iodomethylate and the latter again boiled with pottassium
hydroxide. When the evolution of volatile base (trimethylamine)
had almost ceased the liquid was cooled and shaken out with ether.
118
After removal of the ether, methylthebaol (XVI) was left as a thick
syrup. It was analyzed as a picrate.
(Ber. Dtsch. chem. Ges., 1905, 3234.)
Veratrine.
C. Reichard has studied the color reactions of Veratrine. The
veratrine used was the amorphous mixture of alkaloids obtained
from Sabadilla seeds.
With concentrated sulphuric acid veratrine gives a pretty reddish- *
violet color which disappears upon dilution with water and reappears
with gradually increasing intensity upon evaporation of the water.
A mixture of Veratrine and mercuric chloride is colored brownish
by concentrated sulphuric acid.
On adding strong hydrochloric or sulphuric acid to a mixture of
veratrine and sodium iodate a yellow color is developed by the
hydrochloric acid and a black color by the sulphuric acid. In both
cases iodine is set free.
A mixture of veratrine and ammonium molybdate is gradually
colored yellowish by water or hydrochloric acid and blue by con-
centrated sulphuric acid.
Water gradually colors pale yellow a mixture of veratrine and
ammonium metavana.date. Hydrochloric acid (25%) or concentrated
sulphuric acid color this mixture yellow with the formation of a
reddish-brown mass.
Weratrine is colored bluish by tungstic acid in presence of water,
hydrochloric acid or sulphuric acid.
(Jn moistening a mixture of Veratrine and potassium dichromate
with hydrochloric acid a yellow color is developed which soon
changes to green. If sulphuric acid be used instead of hydrochloric
acid the color is at first cherry-red and then green.
A mixture of veratrine and bismuth chloride solution assumes a
yellow color within 12 hours.
A mixture of veratrine and copper sulphate is colored red by
concentrated sulphuric acid and green by hydrochloric acid.
A mixture of veratrine and copper oxychloride is gradually
colored bluish green by water, immediately light green by hydro-
chloric acid and dark green by sulphuric acid.
On adding veratrine and water to a crystal of potassium ferro-
cyanide or potassium ferricyanide and evaporating to dryness a
residue is left which is colored green by hydrochloric acid (25%) in
119
the case of the ferricyanide, whereas with the ferrocyanide the residue
becomes snow white.
When potassium ferrocyanide or potassium ferricyanide is added
to a mixture of veratrine, mercurous nitrate and concentrated sul-
phuric acid, a blue color is developed.
On evaporating veratrine with formic aldehyde (40%) a snow
white residue is left which is colored dirty yellow by strong sulphuric
acid. If a solution of potassium sulphocyanate be used instead of
formic aldehyde the residue gradually assums a yellow color which
disappears upon the addition of strong sulphuric acid.
A concentrated solution of antimony trichloride resinifies veratrine
and colors it brown-black.
In an acid-free solution of ferric chloride veratrine dissolves with
a light yellowish-green color.
Weratrine does not react with cobalt nitrate.
(Pharm. Centr.-H., 1905, 644.)
Yohimbine.
L. Spiegel continues his investigations of yohimboic acid obtained
from yohimbine by means of alkali. On treating yohimboic acid
with methyl alcohol, or absolute ethyl alcohol, or diazomethane the
acid is converted into yohimboic anhydride, C20H24N2O3. As the
anhydride contains neither methoxyl nor N-methyl groups, no alkyl
groups go into it in this transformation. This was also shown by
the fact that when the anhydride is esterified with methyl alcohol
and hydrochloric acid yohimbine is formed and with ethyl alcohol
and hydrochloric acid yohimbethyline is obtained showing that the
anhydride behaves in the same way as yohimboic acid itself, not as
an alkyl derivative of the acid. (See Ber. Dtsch. chem. Ges., 1904,
271.) When the anhydride is recrystallized from water it is recon-
verted into yohimboic acid, C20H26NO4. In the reaction of yohimboic
acid with diazomethane there is formed besides the anhydride a non
crystallizable substance melting at 120–125° and consisting chiefly
of yohimbine yohimboate.
Methylyohimboic acid, C21 H28N2O4, was obtained by the action
of methyliodide upon yohimboic acid in presence of sodium hydroxide.
As no methoxyl group could be found in methylyohimboic acid the
latter must contain a methylimide group. This methylyohimboic
acid is not converted into yohimbine when treated with methyl
alcohol and hydrochloric acid as might be expected.
120
When yohimboic acid is treated with diethylsulphate it is con-
verted into ethylyohimboic acid, C22H30 N2O4.
A molecular weight estimation of yohimbine and yohimboic acid
showed that the former had the formula, C22H28N2O3, and the latter,
C10H18 NO2, which is only half of the formula previously deduced.
As titration with alkali and analysis of the silver salt correspond to
an acid of the formula, C20H26N2O4, it must be assumed that yohim-
boic acid is easily converted by acids or alkalies into a dimolecular
compound, N: C9H12.00.O.NH#C9H12.00.OH. Methylyohimboic acid
would therefore have the following formula, NiCo B 12.00.O.N(CH3); G9-
H120O2H.
Yohimbine is possibly the methylester of this methylyohimbojc
acid though the latter cannot be converted by esterification with
methyl alcohol into yohimbine.
When yohimboic acid is esterified both the hydrogen atom of
the CO2H and that of the NH groups are replaced by alkyl groups.
It is possible that anhydroyohimbine which contains one molecule
of water less than yohimbine and which underlies the formulae of
the salts of the alkaloid is formed from yohimbine in such a way
that H2O is eliminated from the CH3 group attached to the N-atom
and the CO group next to the N-atom.
N N
Ž
CoHºº chº
200 XC
Oć ozº NCH
N — H2O = N ... ."
N.N. c. 2 NN /
/NCH, 2%
CoH 12& Co H1 2N
NCO.O.CH3 NCO.O.CHs
Yohimbine. Anhydroyohimbine.
This supposition is supported by the fact that yohimbine never
gives off the full quantity of methyl iodide when the hydriodide of
the base is heated to a higher temperature. That some methyl
iodide is given off when anhydroyohimbine is heated with hydriodic
acid and the conversion of yohimbine into yohimboic acid by alkalies
can be explained by assuming that in these reaction the ring is split
Open. $.
In several decompositions of yohimboic acid a volatile base was
obtained, the vapors of which had a very penetrating faeces-like
Odor and gave the pyrrol reaction. The base gave no color with
nitrous acid. (Ber. Dtsch. chem. Ges., 1905, 2825.)
Northwestern University, School of Pharmacy.
sº ºw. “
• . ." ſº.
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Up to 1899. . . By W. O. Richtmann and J. A. Anderson.
Brochure, pp. 180. $1.00.
5. Bibliography of aromatic waters. From 1809 to 1900, incl.
By W. O. Tichtmann. Brochure, pp. 219. $1.00
In addition to the pamphlet form, these bibliographies will be found
very convenient for card catalogues which can be kept up to date as indi-
cated by the following fascimile reproduction of such a card.

The Volatile Ols: 1905.
By I. W. BRANDEL.
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The Volatile Oils: 1905.
By I. W. BRANDEL
M ILWAUKEE,
Pharmaceutical Review Publishing Co.
1907.
4….tº
º: -/f 'ſ 3 %r.
OILS OF THE HEPATICAE.
3 al. Oil from Mastigobryum Trilobatum.
. The liverwort, Mastigobyrum trilobatum L., grows in the
Black Forest. It loses 90 p. c. upon drying and the dried material
yields 0.93 p. c. of an orange yellow oil, having a cedarwood-like
odor. d.12° = 0.945–0.947°; an in 42.26 p. c. alcoholic solution =
+ 5.10°. The oil contains a small amount of an aldehyde and a free
acid. Saponification number 5.4. Most of the oil boiled from 260°
to 270° and the fraction had a blue color. 1
3 b. Oil from Leioscyphus Taylosi.
Mueller 2 obtained 1.6 p. c. of a bluish-green oil from Leioscyphus
taylosi, Hook, which had a very peculiar odor and an unpleasant
taste. d20° = 0.978–0.986; [a]n = — 3.44° in 9.03 p. c. alcoholic
solution. Saponification number 11.4. Oil boils above 260° C. and
probably contains sequiterpenes and sequiterpene alcohols.
3 c. Oil from Madothera levigota.
The liverwort, Madothera levigota, Schrad., collected near
Muenich, yielded 0.9 p. c. of a thin pleasant smelling, orange yellow
oil. d.16° = 0.856; [0] p = + 72.74°. The pepper like taste of the
liverwort is not due to the Oil.8
3 d. Oil from Alicularia Scalaris.
The liverwort, Alicularia scalaris, Corda., yields a yellow oil
which has a sp. gr. of 0.965; ap == —33.49°. 4
OILS OF THE ABIETINEAE.
4. American Oil of Turpentine. G.-H...-K., p. 239.
Vol. Oils: 1904, p. 1.
Properties. Reuter 5 has determined that the mother liquors
from the manufacture of terpin hydrate contain from 5 to 9 p. c. of
eucalyptol.
1 Ztschr. physiol. Chem., 45, d. 299.
2 Ztschr. physiol. Chem., 45, p. 299.
3 Ibidem.
4 Ibidem.
5 Midland Drugg., 1905, p. 422.
2 THE Wol ATILE OILs: 1905.
Adulteration. To determine the purity of oil of turpentine,
Vaubel 6 recommends the determination of the bromine number. His
method is: -
Carefully weigh out 1–2 gm. of the oil to be tested and dissolve in 100
c. c. of glacial acetic acid. Add 5 gms. of potassium bromide and 20 c. e.
of fuming hydrochloric acid, and then from a burette add a standard Solu-
tion of potassium bromate until bromine is no longer absorbed. The end,
reaction is determined by the bromine color of the solution or with
potassium iodide paper. 100 gms. of pure American oil will absorb from
220 to 230 gms. of bromine. -
According to Valenta, 7 the presence of pinolin (resin essence) in
turpentine oil can not be detected from the refraction and rotatory
power of the various fractions of the oil. If pinolin is present, por-
tions of the oil distilling over below 160° will give an intense green
color with acetic acid anhydride and a drop of sulphuric acid or if
one part of the oil is mixed with 1 to 2 parts of a 6 p. c. solution
of iodine in chloroform and carefully heated.
As a test for pine tar oils the following is recommended:
Equal volumes of a 1 p. c. gold chloride solution and , of the oil to be
tested are thoroughly mixed after being heated on a water bath for one
minute. Pure turpentine oils show a separation of gold only in the oil film,
the aqueous solution remaining colorless. If pine tar oils or pinolin are
present, the entire gold solution becomes discolored.
The requirements of various new Pharmacopoeias for oil of
turpentine are:
U. S. Austria. - Spain.
Sp. gr..............0.86–0.870 (25°)1 0.865–0.87 (15°) 0.85–0.87 (15°)2
Rect................. ().860–0.8653 0.860–0.87 () *º-
B. P............... • - 1559–1629 1609—4 * -
Solubility........ 3 vol. 92 p.c. alc. 8 parts of alcohol. 4 vol. 90 p. c alc.5
- 12 vol. 81 p. c. alc.
To detect pine tar oil in turpentine oil Utz's uses the following
reaction : -
Equal volumes of the oil to be tested and a solution of stannous chloride
are mixed. If the oil is pure, the stainous chloride solution becomes yellow
or orange-yellow, while in the presence of pine tar oil, the reagent acquires
a raspberry red color.
Utz has determined the following iodine numbers:
Ztschr. f. Öffentl. Chenn., 11, p. 429.
Chem. Ztg., 29, p. 807. -
Chem. Rev., Fett- und Harz-Ind., 12, p
I, Ower limit should be () 858. S. & Co
Upper limit should be 0.877. S. & Co.
Lower limit should be 0.853. S. & Co.
Should be 1:55°. S. & Co. - . -
Sol. in 5–7 vol. 90 p. c. alcohol and 12–14 vol. 81 p. c. alcohol, S. & Co.
. 99.
:
.º.
*

HEPATICE, ABIETINEE. 3
American turpentine oil ...................................... 331.64
French & 4 “...................................... 223.51
German & 4 “ (Pine tar oil).............. 169.75
Austrian { { “...................................... 277.94.
Greek & 4 “...................................... 260.29
Russian & 4 “ (Pine tar oil).............. 181.71
5. French Oil of Turpentine. G.-H...-K., p. 247.
When neutral and completely dried oil of turpentine is distilled,
the optical rotation of the distilled oil does not differ from that of
the original oil. If the oil is slightly acid or saturated with moisture,
the optical rotation of the distillate becomes less (–35 to —27).
After a few months the oil regains its original rotation.”
7 a. Greek Turpentine Oil. Vol. Oils: 1904, p. 3.
According to Schimmel & Co.,10 Greek oil of turpentine has the
following properties: dis? = 0.8631; ap = + 38° 41'; no 20° =
1.46555; ester number 4.5; soluble in 6 volumes of 90 p. c. alcohol.
27 p. c. of the oil boiled from 158° to 159° and 16 p. c. from 159°
t;O 160°.
7 b. Indian Oil of Turpentine. Vol. Oils: 1904, p. 4.
The oleoresin from Pinus longifolia, Roxb., is white, opaque, very
viscous and of a granular nature. It had an agreeable odor re-
minding of limonene. Rabak 11 obtained 18.5 p. c. of oil from the
oleoresin, having a sp. gr. 0.867; an = + 2°48'. 56 p. c. of the oil
boiled from 165–170° and the fraction had ap = —2°. l-pinene and
d-limonene are probably present although no crystalline derivatives
could be obtained.
8. Turpentine Oil from Larix Europaea. G.-H. K., p. 249.
The oleoresin from Larix europaea, growing in the United States,
is a thick, light yellow liquid. Sp. gr. 1.0004 at 22°; an of a 5 p. c.
solution in alcohol + 2°20'; acid number 60. Upon steam distilla-
tion Rabak 12 obtained 13.5 p. c. of oil; sp. gr. at 22° 0.867;
[a]n = +2°36′. The oil contained pinene (nitrol benzylamine).
9 Ann. Chim, anal, appl., 10, p. 146.
10 S. & Co., Rep., Oct.–Nov., 1905, p. 67.
11 Pharm. Rev., 23, p. 229.
12 Pharm. Rev., 23, p. 44.
4 THE Wol,ATILE Orls: 1905.
9 b. Turpentine Oil from Abies amabilis.
Abies amabilis, an Oregon fir, yields a very liquid, pale yellow
oleoresin which has a decidedly limonene-like odor. Its sp. gr. at
22° = 0.969; acid number 44. Distillation with steam yields 40.3
p. c. of a colorless oil 18 which also has a limoneme-like odor. Sp. gr. at
22° = 0.852; [a]n = –14°28'. 43 p. c. of the oil boiled from 160°
to 170° and 49.6 p. c. from 170°–180°. The oil contains l-pinene
(nitrol benzylamine, m. p. 121°) and 1-limonene (nitrol benzylamine
m. p. 97°).
l
PINE TAR OILS. – KIENOELE.
18. Pine Tar Oil from Finland. G.-H...-K., p. 257.
Vol. Oils; 1904, p. 6.
Prep a ration. According to Utz 14 a me; hod is used in Finland
for the production of pine tar oil, which differs from the methods
commonly used and produces a far superior oil.
In this method, water vapor, superheated to a definite tempera-
ture of several hundred degrees, is passed through a series of iron
retorts filled with pine wood, the vapor laden with oil being reheated
before passing into each retort. The vapor of . oil and water are
properly condensed and separated. The wood tar collects at the
bottom of each still and is drawn off from time to time. The wood
gases generated are used for heating. The resulting oil contains less
enpyreumatic substances.
Properties. The oil has a sp. gr. at 14° = 0.861; an in 200
mm. tube = + 33.9.2°; no at 15° = 1.4723. The bulk of the oil
|)oils from 1 (5()—162°.
PINE NEEDLE OILS.
20. Oil from Cones of Abies Alba. G.-II.-K., p. 259.
Vol. Oils: 1904, p. 6.
A templin oil distilled by Schimmel & Co.15 from the cones of
Allies alba, Miller, had a strong limoireme odor and the following
constants: Sp. gr. at 15° = 0.8551; an = —76° 58'; ester number
2.44 = 0.85 p, c. bornyl acetate; soluble in 7 volumes of 90 p. C.
alcohol.
is pharm. Rev. 23, p. 46
) .
14 l’h arm. ('entral h., 46, pp. 299, (581.
15 S. & Co., ſtep., () t.—Nov., 1905, p. 59.
PINE TAR OILs, PINE NEEDLE OILs. 5
22. Pine Needle Oil from Pinus Montana. G.-H...-K., p. 261.
An oil sold as oil from Pinus montana, was found to be adult-
erated with American turpentine oil. 16 It had the following proper-
ties: Sp. gr. at 15° = 0.8682; an = + 6°43’; ester number 1.69 =
0.59 p. c. of bornyl acetate; soluble in 7 volumes of 90 p. c. alcohol.
34 p. c. of the oil distilled below 160°, while in the case of pure oil
from Pinus montana practically nothing distills over below 160°.
The oil is official in the Austrian Pharmacopoeia, ed. VIII as
Oleum pini pumilionis. The constants are:
Sp. gr. at 15° = 0.865–0.875.
B. B. — 165°–
Solubility = in alcohol. 1
23 b. Oil from Fir Buds.
By direct distillation of the buds of the Scotch Fir, Pinus syl-
Vestris, Haensel 17 obtained 1.127 p. c. of a yellow oil. By cohoba-
tion the yield was increased to 1.47 p. c. The first oil had dis? =
0.8839; ap = —22°; saponification number 19.5; saponification
number after acetylation 58; 1 gram is soluble in 20 grams of 80
p. c. alcohol.
The cohobated oil had sp. gr. at 15° = 0.9588; ap = —5.44°;
saponification number 33; saponification number after acetylation
= 144; 1 gram is soluble in 15 grams of 80 p. c. alcohol. The oil
contains a much larger percent of borneol than does the needle oil
from this same species.
29 a. Oil from the Cones of Pinus Maritima.
Seestrand kieferoel.
Properties. Iłelloni 18 has distilled the fresh and also the dried
comes of Pinus maritima, Mill., with the following results:
Fresh cones. Dried cones.
Solubility in 90 p. c. alcohol.... 1 : 10 1 : 10
Yield......................................... 0.681 p. c. 0.517 p. c.
Color........................................ light green light green
Sp. gr....................................... (), 8810 0.9963
%D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . —23°46’ —20° 15'
[40] at 15°.............................. —26.51 8° –22.355°
Acid number............................ O 5.43
Ester number........................... 7.9 = 2.77 p. c. 8.27 = 2.92 p. e.
Saponification number............. 7.9 1:3.7
16 S. & Co., Rep., Oct —Nov., 1905, p. 59.
17 Haensel's Ber., April, 1905, p. 18.
18 Estr. dall. Ann. (ſella Soc. Chim. di Milano, 11, p. —.
1 Sol. in 5–8 vol. 90 p. e. a 'cohol with turpidity at times. S. & Co., April
1906, p. 82.
6 THE WOLATILE OILS : 1905.
The oils contain no aldehyde. The free acid from the oil of dried
cones is caprylic acid. The esters are compounds of acetic, propionic,
caprylic and laurinic acids. The oil consists principally of l-pinene
(nitrol piperidide, m. p. 118°) and probably also contains limonene
or dipentene and borneol.
33. Thuja Oil. G.-H...-K., p. 267. Vol. Oils: 1904, p. 9.
The difficulty of preparing fenchone derivatives from impure
fenchone is well known. To prepare the semicarbäzone from pure
fenchone, Wallach 19 dissolves 10 grams of the fenchone in 50 c. c. Of
alcohol, adds 10 grams of semicarbazone hydrochloride and 40
grams of sodium acetate in 20 c. c. of water and allows the mixture
to stand for two weeks. The solution is then poured into water and
the excess of fenchone distilled off with steam. If the fench One con-
tains camphor etc. the oil is treated with an excess of semi-carba-
zone solution as above which will readily combine with the camphor
and the fenchone can be distilled off and then converted into the
semicarbazone.
Fenchone-semicarbazone melts at 182°–183°. The d-fenchone
derivative has ap in 8.1 p. c. sol. in methyl alcohol of + 47.04° and
the ap for the l-fenchone in a 5.506 p. c. solution is —46.88°.
Haller 20 has prepared several alkyl thujones by adding alkyl
iodide to a solution of thujone in ether in which the required amount
of sodamide has been dissolved. The product are liquids having an
odor like that of thujone. The following table contains the constants
of thujone and its alkyl derivatives.
H. P. (, D at 15°. Sp. gr. at 15°. entiºn.
Thujone............. 84.5° (13 mm.) –– 68° 0.9126 (20°) 1719
Methyl thujone.. 90.0° (16 mm.) + 16° 16' 0.91 ()2 1649
Ethyl thujone.... 93–96° (13 mm.) — 4.8° 23' (). 9155 1310
Propyl thujone..107°–110° (16 mm.) —50.47' ().92:54. 130°
35. Oil of Cypress. G.-H...-K., p. 269. Vol. Oils: 1904, p. 9.
The physical constants of the French cypress oil which is distilled
from fresh leaves and the German oil which is (listilled from dried
leaves lie within the following limits * :
19 Nachr. R. Ges., Wiss. Goettingen, 1905, p. 6.
20 Compt. rend., 140, p. 1626.
21 S. & ('o., Rep., April–May, 1905, p. 26.
PINE NEEDLE OILs. 7
French oil. German oil.
Sp. gr. at 15°......... tº gº tº s tº e g g tº e º e º a s tº º is & s e º 'º we & tº it wº 0.868–0.878 ().88–0.892
*..…. º g g g g g e s ∈ s e º ºs e º is g º e º is tº s º º a º tº tº dº º & e º e & e º is s & 4, as tº e e +22° to +31° +4° to +18°
Acid number............ tº e º 'º e º is a tº gº ºn tº e º sº tº s tº as e s tº g tº g º m a O 1.5–3.0
Ester number...................... © tº & © tº tº tº $ tº e º ſº ſº e º is j–1() 1.5–22
Ester number after acetylation......... 10—1.5 43–49
Solubility in 90 p. c. alcohol............. 5–6 vol. 2–6 vol.
35 a. Oil of Cypress Fruits.
An oil distilled from the fruits of Cupressus Sempervirens, L., had
a sp. gr. at 15° = 0.8686; a p = + 30°48'; acid number 0; ester
number after acetylation 12.78; soluble in 6 vol. of 90 p. c.
alcohol. 22
35 b. Oil of Cupressus Lambertiana.
The oil from the leaves of Cupressus lambertiana a tree which is
often found in the gardens of southern France, differs entirely from
ordinary cypress oil. ** The yellowish-green oil has a melissa, like
odor; sp. gr. at 15° = 0.8756; a p = + 31°53'; acid number 1.5;
ester number 13.9; ester number after acetylation 50.82; soluble in
9–10 volumes of 80 p. c. alcohol. The yield of oil was about 0.1 p. c.
37. O11 of Juniper Berries. G.-H...-K., p. 270.
According to Stroecker 24 the Hungarian juniper oil, which is
obtained as a by product in the manufacture of gin, is equal in
quality to the distilled oils. It is a colorless liquid with a balsamic
odor. Sp. gr. = 0.865–0.900. Oil of juniper berries is official in the
United States Pharmacopoeia, 8th ed., and in the Austrian, 8th ed.
U. S. Austrian.
Sp. gr.................... ....0.860–0.880 (25°)* 0.865–0.880 (15°)+
Solubility...................10 vol. of 90 p. c. alcohol. Little soluble. £
39 a. False Savin Oil.
The difference in the commercial French savin oil as compared
with the German and English oils, has always been explained by
assuming that the savin oil distilled in France entered the market
22 S. & Co., Rep., April–May, 1905, p. 26.
28 S. & Co., IRep., April–May, 1905, p. 83.
24 Pharm. Post, 1905, p. 236.
* Lower limit should be 0.854. S. & Co.
# Should be 0.860–0.885. S. & Co. Umney & Dennett.
# TFreshly distilled oil is soluble, but the solubility decreases with age. S. & Co.,
April, 1906, p. 84.
8 THE WOLATILE OILS : 1905.
only after the addition of a large amount of turpentine oil.” Um-
ney and Bennett,26 however, show that the French oil is obtained
from an entirely different plant. While the English and German oils
are distilled from Juniperus sabima, L., the French oil is wholely Ol'
partly obtained from Juniperus phoenicia. A comparison of the oils
follows:
ICnglish. Gel’man. I'rench.
Sp. gr............................................ (),909 ().920 0.892
“D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . + 68° + 42° + 4° 30'
Esters............................................ 47.6 p. c. 36.5 p. c. 9.3 p. c.
Total Sabinol........ ...................... 52.1 p. c. 48.2 p. c. 17.1 p. c.
Solubility in 90 p. c. alcohol...... 1 : 1 1 : 1 1 : 5
}
The French oil contains about 75 p. c. of pinene (hydrochloride,
m. p. 125° C.; nitrosochloride, m. p. 107°C.) and also cadinene and
an aldehyde.
41. Oil of Savin. G.-H...-K., p. 273.
From 100 lbs. of savin which had been kept for more than half
a year, Ziegelman 27 obtained 0.01544 p. c. of oil. The oil was light
amber in color and had a sweet terbinthinate odor. Sp. gr. at
25° = 0.91329; ap = +0; soluble in one vol. of 90 p. c. alcohol;
acid number 6.53—7.33; ester number 109.1–111.9 (37.8–38.95
p. c. of sabinyl acetate); Saponification number 115.73–119.23.
The aqueous distillate when shaken with petroleum ether yielded
0.03822 p. c. of a much darker colored oil. Sp. gr. at 25° = 0.91.33
at 25°. From the yield and properties of the oil, it is readily seen
that the commercial savin oil can not be prepared from the com-
mercial savin drug.
The U. S. Pharmacopoeia, 1905 has the following requirements
for oil of savin : Colorless or yellow ; d.25° = 0.903–0.923; an 25° =
+40° — + 60°; soluble in 0.5 vol. of 90 p c. alcohol.
44 a. Oil of Japanese Cedar.
According to Keimazuº the oil from the Japanese cedar,
(Typtomeria japonica, contains a dextrogyrate sesquiterpene, called
cryptene. It forms a dihydrochloride. The oil also contains a
polyatomic phenol which yields a dibromide, C11H14 Br2O3.
2.5 G.-II. K., p. 27 5.
26 Pharm. Journ., 75, pp. 827, S34).
27 Pharm. Rev., 23, p. 22.
28 Journ. Pharm. Soc. of Japan, 1905, p. 189,
GRAMINEE. 9
OILS OF THE GRAMINEAE.
46. Palmarosa (East Indian Geranium Oil.)
G.-H...-K., p. 281. Wol. Oils: 1904, p. 10.
From a large quantity of palmarosa oil, Schimmel & Co.29 iso-
lated methyl heptenone. The ketone regenerated from the bisulphite
addition product, had a boiling point of 172°; d.15° = 0.856; no 20° =
1.44015; ap = +0. Its semicarbazone melted at 135°.
47. Ginger-grass Oil. G.-H...-K., p. 285. Wol. Oils: 1904, p. 11.
Ginger-grass oil has always been regarded as an inferior quality
of palmarosa oil, or as a mixture of the latter with turpentine or
mineral oils.80 According to Walbaum & Hüthig 81 this oil is ob-
tained from a definite but different plant from that of the palmarosa
oil. Pure ginger-grass oils have the following constants:
Sp. gr. at 15° = 0.927.7–0.9458.
ap = — 29°25'— +22° 40'.
Acid number = 0.9—3.2.
Ester number = 9.5–24.0.
Saponification number after acetylation = 130–172.
Soluble in 1 vol. 80 p. c. alcohol and 2–3 vol. of 70 p. c.
Composition. The oil was found to contain d-a-phellandrene
(nitrite, m. p. 120°; ap = + 44°40'); dipentene (nitrolbenzylamine,
m. p. 110°). 0.2 p. c. of an aldehyde C10H16O, (semicarbazone, m. p.
1699–170°: oxime, m. p. 115°–116°) which oxidizes readily to an
acid, m. p. 106°–107°. The acid contains a double bond, forming
a dibromide melting at 116°. The aldehyde reduces to an alcohol
which boils at 89°–91° (4 m. m.) 236°—238° (755 m. m.). Its
phenylurethane melts at 100°–101°.
i-Carvone (oxime, m. p. 93°–94°) in small quantities and 50–60
p. c. of two alcohols geraniol (phenylurethane, m. p. 82°) and
dihydrocuminic alcohol are also present. The latter alcohol pre-
dominates and exists in the oil in both laevo and dextro modifica-
tions. It boils at 226°–227° (767 m. m.); an = — 13°18’ and
+ 12° 5'.
; ; ; Gº; eºsépril–May, 1905, p. 47.
80 G.-H...-K., p. *
81 Journ. prakt. Chenn., 71, p. 459.
10 The Vol.ATILE OILs: 1905.
48. Lemon-grass Oil. G.-H...-K., p. 285. Vol. Oils: 1904, p. 12.
Preparation. Lemon-grass oil is distilled in Java, chiefly in
three places, Tiitiourouk, Kediri and Tjiaoui. About 300 kilos of
lemon-grass yield I kilo of oil.”
Schimmel & Co. 88 found the oil distilled from fresh plants an in-
ferior product, as shown by the constants: dis” = 0.9123; a d =
— 0°15'; aldehyde content 60 p. c.
Citral. According to a patent of Maschmeyer 84 citral can be
condensed with an ester of a monohalogenated acetic acid in presence
of an alkali alcoholate. The product may be regarded as a citry-
lidene alkoxyacetic ester having the constitution:
CoEI150H=C(OR)(COOR’)
These aliphatic compounds are converted into their cylic isomers
of which there are two, a and 8. The 3-compounds predominate
when con. Sulphuric acid is used at 0°, the a-compounds with cold
dilute acids. These cyclic compounds have the odor of violets.
A compound also having an intense odor of violets, has been
obtained by Dupont 85 by condensing citral with monochloracetone
in presence of sodium methylate, baryta water or sodium amide and
converting the resulting substance into a cylic compound by means
of phosphoric acid. The compound distils at 140°–150° (12 m. m.).
The so-called pseudo compounds obtained by condensing citral
or lemon-grass oil with acetone or with aceto-acetic ester by means
of acids or alkalies, are converted into compounds possessing the odor
of violets, by heating them with water to 170°–190°.80
Adulteration. Parry 87 reports the adulteration of lemon-
grass oil with citronella oil. This was determined from the high
alcohol content and the presence of citronellal. The constants of
the oils were normal.
According to Schimmel & Co. 88 lemon-grass oil is sometimes
adulterated with cocoa, butter.
49. Oil of Vetiver. G.-H...-K., p. 289. Vol. Oils: 1904, p. 10.
The oil distilled from the fresh roots has a bright yellow color;
dit,” = 1.0023; ap = + 33°42'; acid number 16.06; ester number
32 Journ. d'agric. tropicale, 5, p. 42.
33 S. & Co., Itep. April–May, 1905, p. 84.
84 Eng. Pat., 13, 347.
35 Fr. Pat., 355, 315.
36 Ger. Pat., 157, 647.
37 Chem. & Drugg., 66, p. 140. *
38 S. & Co., Itep. Oct.–Nov., 1905, p. 44.
GRAMINEAE, ZINGIBERACEAE. 11
12.16; ester number after acetylation 142.35; soluble in 1 and more
volumes of 80 p. c. alcohol.
50. Citronella Oil. G.-H...-K., p. 291. Wol. Oils: 1904, p. 12.
Dunstan 8° gives the following comparison of Malayan, Java, and
Ceylon citronella oils:
Malay. Java. Ceylon.
Sp. gr. at 15°.................... 0.8948 (). 892 0.903
nd at 24°............................ 1.4858
ad at 24°............................ —1° 34' –0° 50'-2° 26' —9° 36'
Solubility in 80 p. c. alc.... 1:1 1 : 1 1 : 1
Geraniol content................ 32.7 p. c. 31.9—38.1 p. c. 32.9 p. c.
Citronellal content.............55.3, p. c. 50.4–55.3 p. c. 28.2 p. c.
Schimmel & Co. 40 have observed a sample of citronella oil from
Marseilles which was adulterated with 11.2 p. c. of alcohol, and an-
other sample which was largely adulterated with lemon oil terpenes.
Adulterated Oils:
Normal oil. I. IJ.
Sp. gr. at 15°.......................... 0.900–0.9.20 0.8899 0.8852
GD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . () to —21° –9° 15' + 11° 44'
Geraniol................................... 57 p. c. -- 67.3 p. c. 29.6 p. c.
Solubility in 80 p. c. alcohol. 1: 2 1 : 1 1 : 10
OILS OF THE ZINGIBERACEAE.
72. Ginger Oil. G.-H...-K., p. 313. Vol. Oils: 1904, p. 13.
Haensel 41 obtained 1.5 p. c. of oil from the Cochin ginger. The
following table contains the constants of the oils from Cochin and
African ginger:
Cochin. African.
Sp. gr. at 15°....................................................... 0.8826 0.8795
ap in 20 p. c. alcohol sol. in 50 m. m. tube....... —4.30° —4.14°
Saponification number......................................... 17 13.5
Solubility in 80 p. c. alcohol............................... 1 : 65 1 : 65
An oil distilled from African ginger by Schimmel & Co. had sp. gr.
at 15° = 0.8853; an = 42° 16'; no 20° = 1.492.62; saponification
number 6.2; Saponification number after acetylation 42 = 9.8 p. c.
of free alcohol C10H18O.
Besides camphene, phellandrene and Zingiberene, previously
identified, the oil was found to contain cineol (iodol compound,
m. p. 112°); borneol, m. p. 204°; citral (citryl-8-naphthocinchominic
acid, m. p. 197°), and an alcohol, possibly geraniol.
39 Chem. and Drugg., 67, p. 904.
40 S. & Co., Rep., Oct.–Nov., 1905, p. 19.
41 Haensel’s Ber., April, 1905, p. 15.
12 THE WOLATILE OILS : 1905.
73 a. Oil of Amomum angustifolium.
The fruits of Amomum angustifolium, Sonnerat, growing in
western Africa, yield upon distillation 1.6 p. c. of oil. Sp. gr. at
15° = 0.9030; ap = —6.82°; saponification number 50; saponifica-
tion number after acetylation 107; 1 gram sol. in 1 gram 80 p. c.
alcohol.42
73 b. Oil from Amomum mala.
The fruit of Amomum mala, growing in the forests of eastern
Africa, yields upon distillation 0.76 p. c. of a brownish-yellow oil.
Sp. gr. at 15° = 0.9016; an = –10°54'; acid number 3.5; ester
number 1.7; ester number after acetylation 67.05; forms a cloudy
solution with 1:1.5 vol. of 80 p. c. alcohol. The oil contains much
cineol (iodol compound, m. p. 112°).
OILS OF THE PIPERACEAE.
84. Oil of Cubebs. G.-H...-K., p. 322.
The oil of cubebs is official in the 8th edition of the U. S. Phar-
macopoeia with the following requirements:
Colorless, light green or yellow; des° = 0.905–0.925; ad 25° = —25° to
409. OILS OF THE BETULACEAE.
96. Sweet Birch Oil (Wintergreen Oil).
Ziegelman 48 has determined by colorimetric estimation, that the
largest percent of oil is obtained by macerating the birch bark for
12 hours and then distilling.
By distilling 45.14 kilo of bark in this way 0.306 p. c. of oil
which separated and 0.076 p. c. of cohobated oil (total = 0.383 p. c.)
were obtained. This yield was, however, only one-half of the yield
calculated from the estimation. The combined oil had a sp. gr. at
25° of 1.1559 and contained 90.959 p. c. of methyl salicylate. The
oil was soluble in 4 parts of 70 p. c. alcohol. 4.
The oil of Betula lenta, L., is official in the U. S. P. 8th edition.
It should be optically inactive, and its other properties are the same
as gaultheria oil.
96 b. Oil from Birch Buds.
Soden and Elze 44 obtained 4.3 p. c. of a thick yellow oil from
the birch buds. It had a strong, peculiar odor and is soluble in
T & Haensers, Ber; Sept. 1905, p. 9,
43 Pharm. Rev., , p. 83
44 Ber., 88, p. 1636,
PIPERACEAE, BETULACEME, MORACEAE, SANTALALCEAE. 13
alcohol leaving a small amount of a crystalline residue, which also
separates out when the oil is cooled to 10° C. The bulk of the oil
boils from 265°–295°; sp. gr. at 15° = 0.975; ap = —2°; acid
number 2.1; ester number 67.2.
An oil distilled by Schimmel & Co.45 had the following properties:
d15°:= 0.9755; ap = —6°14'; no 20 = 1.50179; acid number 1.6;
ester number 73.4; acetylation number 170.5. Soluble in 1 vol. of
80 p. c. alcohol,
The oil contains 47.4 p. c. of a sesquiterpene alcohol, C15H230H,
which Soden & Elze have named betulol, and 31.44 p. c. of its
acetate. Betulol is a colorless, almost odorless oil which has a
bitter taste. Sp. gr. at 15° = 0.975; ap = —35’; b. p. at 745 m. m.
= 284°–288°.
OILS OF THE MORACEAE.
97. Oil of Hops. G.-H...-K., p. 336.
Schimmel & Co.46 have detected the adulteration of oil of hops
with gurjun balsam. The oil had too high a sp. gr. (0.9189 instead
of 0.855–0.88) and ap = —40° instead of + 0°28'.
OILS OF SANTALACEAE.
99. Sandalwood Oil. G.-H...-K., p. 338. Vol. Oils: 1904, p. 16.
According to Schimmel & Co.47 pure sandalwood oil may have
a slightly lower rotation than —17°, which has generally been
accepted as the lower linit.
The oil of sandal capsules, is commonly adulterated with castor
Oil. 48
The following table contains the pharmacopoeial requirements for
oil of sandalwood :
L. S. Austria. Spain.
Sp. gr........ 0.965–0.975 (25°)1 0.975–0.980 (15°)2 0.975–0.985 (15°)
Color......... light yellow light yellow light yellow
O'D. . . . . . . . . . . . . . —16 to —20 * laevo
Solubility. 5 vol. 70 p. c. alc. 5 vol. spir. dil. easily sol.
Santalol.... 90 p., c.8 *E-mºmº -º-º-º-º:
45 S. & Co , Rep , Oct.–Nov., 1905, p. 14.
46 S. & Co., Rep., April–May, 1905, p. 64.
47 S. & Co., Rep., Oct.–Nov., 1905, p. 64.
48 S. & Co., Rep., April–May, 1905, p. 72.
i The upper limit should be 0.980. S. & Co.
2 The upper limit should be 0.985, . S. & Co.
7, The formula is taken as C10H26O instead C10H24O, S. & Co. Rep. April, 1906,
p, 'ſ B,
2
14 THE WOLATILE OILs: 1905.
OILS OF THE ANONACEAE.
119 a. Oil of Monodora Myristica.
Properties. Thoms 49 obtained from the seeds of Monodora
myristica, Dumal, 7 p. c. of a volatile oil. It had a yellow color,
with a yellowish-green fluorescence, an agreeable odor and did not
solidify when cooled, d20° = 0.896; ap = —64.16°.
Schimmel & Co.50 obtained 5.37 p. c. of oil, having the following
properties: dis” = 0.859; ap = –117°40'; acid number 1.36; ester
number 3.4; ester number after acetylation 27.11. Soluble in 4
volumes of 90 p. c. alcohol.
Composition. The oil contains 1-limonene (nitroso-chloride,
m. p. 103°–105°); phellandrene (nitrite, m. p. 114°–115°) and a
substance, C10H16O, probably identical with myristol.
OILS OF THE MYRISTACEAE.
120, 121. Oils of Mace and Nutmeg. G.-H...-K., p. 366.
Wol. Oils: 1904, p. 18. º
The oil of nutmeg is official in the U. S. P. 8th edition and oil
of mace is official in the Austrian pharmacopoeia.
U. S. 8th ed. Austria, 8th ed.
Color............................ colorless or light yellow colorless or yellow
Sp. gr........................... 0.862–0.910 (25°)* 0.890–0.930 (15°)
‘’D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . + 14° to + 28° (25°)+ *-
Solubility..................... 3 vol. 90 p. c. alcohol 3 vol. Of alcohol.
* Upper limit should be 0 924. S. & Co.
# A good oil had -- 7° 52'. S. & Co.
OILS OF THE LAURACEAE.
128. Oil of Camphor. G.-H...-K., p. 370. Vol. Oils: 1904, p. 19.
An oil from the leaves of Laurus camphora, growing in southern
France, examined by Schimmel & Co.,51 has little resemblance to
previously examined distillates. The oil obtained at a yield of 0.52
p. c. was colorless and had a pronounced cardamom-like odor.
Sp. gr. at 15° = 0.9058; ap = —26°12'; acid number 0.34; ester
number 8.82; ester number after acetylation 46.9; soluble in 1 vol.
of 80 p. c. alcohol.
The oil contains pinene (nitrolbenzylamine, m. p. 123°); cineol
(iodol-compound, m. p. 112°); 10 p. c. of terpineol, m. p. 35° (phenyl-
urethane, m. p. 112°). The presence of camphene is probable.
49 Ber. d. d._pharm. Ges. 14, p. 24.
50 S. & Co , Rep., April–May, 1904, p. 63.
51 S. & Co., Itep., April–May, 1905, p. 83.
ANONACEAE, MYRISTACEAE, LAURACEAE. 15
A tree, growing in Alameda Co., Cal., and which appears to be
indigenous, resembles Cinnamomum camphora. The bark has the
odor of Sassafras and the leaves and small branches yield by steam
distillation 0.15 p. c. of camphor of a very pure quality. The cam-
phor from the wood was obtainable only by sublimation at high
temperatures and was not so pure. These trees may become of value
for the production of camphbor.5°
A number of patents for the production of camphor have been
issued.
According to Schering 58 borneol or isoborneol may be oxidized
almost quantitatively to camphor by means of ozone.
According to Richardson 54 artificial camphor (pinene hydro-
clıloride) alcohol, water, sodium hydrate and Sodium formate are
mixed together in the order given and in molecular proportions and
heated for 10 hours to 120°. After cooling the alcohol is distilled
off, the residue acidified and the resulting borneol distilled off and
oxidized in benzene solution with potassium permanganate.
Zimmermann 53 has devised a method in which a mixture of
borneol vapor and oxygen or air at about 190° C., is passed over
SOIſlé catalytic agent like spirals of copper wire or platinised asbestos.
Yield is 25 p. c.
According to Boehringer & Söhne 50 isoborneol can be easily and
rapidly oxidized to camphor by means of chlorine. The oxidation
may be effected by mixing solutions of chlorine and isoborneol or
by passing chlorine gas diluted with some inert gas into a cooled
solution of isoborneol or by the action of chlorine gas on solid iso-
borneol. The yield is almost quantitative.
Behal, Magriner and Tissier 57 produce camphor by oxidizing the
products obtained when 69 parts of lead acetate and 200 parts of
glacial acetic acid are heated to 130°–135° C. or to 180° C. for
2 hours. In the former case camphene is produced and in the
latter case, bronyl and isobornyl acetates.
Bouveault & Blanc 58 consider isoborneol a derivative of cam-
phene and not of camphor. It is regarded as a hydrate of camphene.
52 Am. Drugg., 1905, p. 315.
53 Eng. Pat., 1905, No. 8297.
54 Eng. Pat., Applic. No. 5549.
55 Engl. Pat., 9008.
56 Engl. Pat., 28.035.
57 Fr. Pat., 349,896.
58 Compt. rend., 140, p. 93.
16 THE WOLATILE OILs: 1905.
C8H14 = C = CH2 Cs H14 = COH-CH3
Camphene. Isoborneol
It is therefore a tertiary alcohol.
129. Oil of (Ceylon) Cinnamon. G.-H...-K., p. 377.
Vol. Oils: 1904, p. 19.
In the distillation of cinnamon chips, Haensel 59 obtained a light
and a heavy oil in the proportion of 2:1. The oils have the follow-
ing properties:
Light Oil. Heavy oil.
Sp. gr............................................................. 0.996 1.025
“d in 50 m. m. tube...................................... 0.62° too dark
Aldehyde content........................................... 47 p. c. 67 p. c.
The U. S. P. 8th ed. and the Spanish Pharmacopoeia 7th ed.
have the following requirements for cinnamon Oil:
|U. S. 1 Spanish.
Color................................. yellow or brown yellow or red
Sp. gr................................ 1.045—1.055 (25°)2 1.004—1.006 (15°)3
* D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . —19 to +1° slightly laevo
Solubility.......................... 2 vol. 70% alcohol g====
Cinnamic aldehyde............ 75 p. c. *-
The requirements for cinnamic aldehyde which is official in the
U. S. P. and Austrian Pharmacopoeia are:
U. S. Austria.
Color..................... ...................... colorless4. yellow
Sp. gr.................. ........................ 1.047 (25°)5 1.054—1.056 (15°)6
(4D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . =E () *
B. p............................................. 2500 *E=mº
M. p............................................ —7.5° *===
Aldehyde..................................... 95 p. c. tº-º-º:
Solubility.................................... in alcohol in alcohol
132 a. Oil of Horse Cassia.
The bark of Cassia grandis, growing in the West Indies, differs
from ordinary cassia in that it possesses a powerful and disagreeable
odor. Steam distillation gave 0.02 p. c. of a perfectly white crystal-
line substance having a combined balsamic and alliaceous odor.60
145. Sassafras Oil. G.-H...-K., p. 395.
The following are the pharmacopoeial constants for sassafras oil:
69 IIaensel's Ber., Sept. 1905, p. 41.
60 Pharm. Journ , 75: p. 788.
The requirements can be required only for a rectified oil. S. & Co.
The upper limit should be 1.059. S. & Co
Should be 1.023–1.040 (15°). S. & Co.
Should be yellow. S. & Co.
Should be 1.048—1.052. S. & Co.
Upper limit should be 1.056. S. & Co.
:
CRUCIFERME. 17
U. S., 8th ed. Spånish, 7th ed.
Color............................ yellow or reddish yellow or reddish
Sp. gr.....................…. 1,065—1.075 (25°) 1 above 1 (15°)
49................................. not above +4° dextro
Solubility..................... in every proportion in 90 p. c. 4 to 5 vol. 85 p. c.
alcohol? alcohol
Safrol is official in the U. S. P. 8th ed. with the following con-
stants: d25°=1.105—1.106 (should be 1.105—1.107. S. & Co.);
ap = +0; b. p. 233; soluble in an equal volume of alcohol.
154 a. Tetranthera Oil.
Both the leaves and bark of Tetranthera polyantha War. citrata
Nees., a tree growing in tropical Asia and known in Java by the
name “Ki-lemolo”, contain an oil.
Oils distilled by Schimmel & Co.60 had the following constants:
Oil from bark. Oil from leaves.
Yield................. 's e < * * * * * * * * * * * * * * 0.81 p. c. 5.42 p. c.
Color.................................. lemon-yellow bright-yellow
Sp. gr. at 15°....... .......... O.8904. ().9042
*D ...................................... +10° 11’ —15°41’
Solubility........................... 1 vol. of 80 p. c. alc. 3 vol. of 70 p. c. alc.
The oil from the bark contains a mixture of citral and citronellal
(naphthocinchoninic acid 220°–225°) while the the leaf oil contains
only citral, about 30 p. c. (naphthocinchoninic acid m. p. 198–200°).
}ineol was also detected.
OILS OF THE CRUCIFERAE.
161. Oil of Mustard. G.-H...-K., p. 409. Vol. Oils: 1904, p. 22.
The requirements of the new pharmacopoeias for mustard oil are
given in the following table:
U. S. Austrian. Spanish.
Color................... colorless or light colorless or colorless or yellow
yellow yellow turning red.
Sp. gr.................. 1.013–1,020 (25°) 1.016—1.025 (15°) 1.018 (15°)
B. p..................... 1489—1529 1489—1529 1489
Allyl isothio-
cyanate............ 92 p. c. e- -*.
163 a. Oil from Cardamine amara.
Cardamine amara, is a plant used in Schlesien in place of water-
cress. Feist 91 obtained 0.0357 p. c. of a mustard oil which comes
60 S. & Co., Rep., April 1905, p. 85.
61 Apoth. Zeg., 20, p. 832
1 flºwer limit should be i.068. S. & Co.
2 Should be 1 to 2 vol. 90 p. c. alcohol. S. & Co.
18 THE WOLATILE OILS : 1905.
from a glucoside and consists of Secondary butyl isosulphocyanate
(thiosinamine. m. p. 134°–135°).
OILS OF THE ROSACEAE.
171. Oil (Otto) of Rose. G.-H...-K., p. 423. Wol. Oils: 1904, p. 23.
History. The art of distilling was discovered by the Arabs,
and the oil first distilled was rose oil. With regard to the discovery
of the oil, it is reported that the Consort of the Emperor Jehanger
observed a thin film on the surface of the canals of the Imperial
Gardens which had been fed with rose water; this film she had
collected and to the fragrant oil thus skimmed off she gave the
name of her husband, A tr-i-Jehāngiri. 92
Oil of rose is official in the 8th edition of the United States and
Austrian pharmacopoeias.
U. S. Austria.
Color..................................... Light yellow yellow
Sp. gr.................................... 0.855–0.865 (25°)* 0.855–870 (15°)
Sapon. No............................ 10–17 F
Solidif. pt............................. 189–22° 3. 159—229
Solubility............................. -*- 30 vol. of alcohol Ś with
slight turbidity.
172. Oil of Bitter Almond. G.-H...-K., p. 436. Vol. Oils: 1904, p. 25.
Oil of bitter almonds and benzaldehyde are official in the 8th
edition of the U. S. P. and the oil in the Spanish pharmacopoeia,
7th ed.
U. S. Spanish.
Oil. Benzaldehyde. Oil.
Sp. gr............ 1.045—1.060 (25°)1 1.045 (25°) 1.043 (15°)2
%D. . . . . . . . . . . . . . . . . . ==O 3 +:0 -E0
B. p............... about 180° 1799–1809 -
Solubility......1 vol. 70 p. c. alc.4 in alc. in all prop. 30 vol. of water 5
Benzaldehyde 85 p. c. 6 85 p. c. -
HCN.............. 2–4 p. c. 2 - -*
174 a. Oil from Geum Urbanum. Vol. Oils: 1904, p. 26.
Bourquelot & Herissey 68 have liberated a glucoside from the
62 Calcutta Rev., 1904, p. —; S. & Co. Rep., Oct.–Nov., 1905, p. 85.
63 Compt. rentl., 140, p. 870.
* Upper limit should be 0.867. S. & Co.
Good oils have Sapon. no. of 8.5–19. S. & Co.
Should be 23.5°. S. & Co.
Paraffin separates. S. & Co.
Should be 1.038—1.063. S. & CO.
Should be 1.045—1.070. S. & CO
Oils are sometimes slightly active. S. & Co.
Should be 1–2 volumes. S. CO.
Does not form a solution with water. S. & Co.
The method of assay is not reliable. S. & Co.
Oils can not always be guaranteed thus. S. & Co. Umney & Bennett.
ROSACEME, LEGUMINOSAE. 19
root of Geum urbanum, called geine, which is decomposed into
eugenol. The eugenol was identified by means of its benzoyl com-
compound. From the fact that emulsion or other enzymes do not
hydrolize the glucoside, the presence of a new enzyme, called grase,
is maintained.
OILS OF THE LEGUMINOSAE.
175. Oil of Copaiba. G.-H...-K., p. 445. Wol. Oils: 1904, p. 26.
Schimmel & Co. 94 have examined the oils distilled from three
samples of pure copaiba balsam.
A sample of Para copaiba balsam yielded 62.5 p. c. of a yellow
oil, which had a balsamic odor. d.15° = 0.9170; ap = — 78°48';
np20° = 1.500.96; acid number 3.14; ester number 0; soluble in 8
vol. of 95 p. c. alcohol.
Bahia copaiba balsam yielded 61.93 p. c. of a faintly yellow oil
which had a balsamic odor and the following constants: — d.15° =
0.8982; an = —9°37'; no.20° = 1.494.60; acid number 7.87; saponi-
fication number 9.82; soluble in 8–10 vol. of 95 p. c. alcohol.
From Angustura copaiba balsam, 52.3 p. c. of oil with a faint
green color a balsamic odor was obtained. d.15° = 0.9161; ap =
–2°20'; no.20° = 1.50169; acid number 10.89; ester number 0;
soluble in 5.5 vol. of 95 p. c. alcohol.
Adulteration. Engelhardt 65 recommends the following as a
very delicate test for gurjun oil in copaiba balsam :
Four drops of nitric acid, sp. gr. 1.42, are mixed with 1 c. c. of glacial
acetic acid and 4 drops of the balsam are floated on the mixture. In the
presence of gurjun balsam a red color is produced at the zone of contact.
Copaiva oil is official in the 8th edition of the U. S. P. an oil e
being required which has d25°= 0.895–0.905 (upper limit should be
0.915, S. & Co.); ap = laevo; soluble in 2 vol. of alcohol. (1 vol.
is soluble in 5–10 vol. alcohol. S. & Co.)
176 a. African Copaiba Balsam Oil. G.-H...-K., p. 446.
The so-called African copaiba is a thick, strongly smelling liquid
containing about 10 p. c. of water and dirt. The purified product
has a dark brown color, with a reddish tinge, is very fluorescent and
has an odor very different from that of other copaibas.
64 S. & Co., Rep., April–May, 1905, p. 24.
65 Pharm. Central h., 46, p. 231.
20 THE WOLATILE OILS : 1905.
By steam distillation, Kline 66 obtained 43.5–45.5 p. c. of a
yellow oil. d.15° = 0.928; an = +5°45'.
182 c. Oil from Hardwickia Binata.
From the red-brown balsam of Hardwickia binata Roxb., a tree
growing in British India, Schimmel 67 obtained 44 p. c. of a colorless
oil, and a brittle green resin remained. The oil had a sp. gr. at
15° = 0.9062; ap = —7°42'; acid number 0.85; ester number 2.88;
soluble in about 5 volumes of 95 p. c. alcohol.
OILS OF THE GERANIACEAE.
183. Oil of Rose Geranium. G.-H-K., p. 449.
Wol. Oils: 1904, p. 28.
Schimmel & Co. 68 report observed adulterations of geranium oil
with esters of benzoic acid, which had probably been added to cause
an apparent increase in the content of geranyl tiglinate.
Umney and Bennett 99 have examined an oil distilled from plants
grown on dry soil. Although only 0.07 p. c. yield was obtained the
oil was exceptionally fine. It had a green color and a very pleasant
odor; sp. gr. = 0.894; ap of first 80 p. c. = 11°; soluble in 2 volumes
of 80 p. c. alcohol. The oil contained 35.6 p. c. of geranyl tiglate
and 71.9 p. c. of total geraniol.
OILS OF THE RUTACEAE.
191. Oil of Buchu Leaves. G.-H...-K., p. 457.
Vol. Oils: 1904, p. 29.
Haensel 79 obtained 1.9 p. c. of a light brown oil which had the
characteristic buchu Odor. Sp. gr. at 21° C. = 0.967. It contained
0.448 p. c. of diosphenol.
By reducing the ketone found in buchu oil Kondakow 71 obtained
a d-menthol. Of the eight possible stereoisomers of menthol, 5 are
known.
196. Oil of Lemon. G.-H...-K., p. 465. Vol. Oils: 1904, p. 29.
California, may in the course of time be a source of lemon oil.
An oil expressed by hand, from the ripe fruit, had a very pleasant
odor, but was somewhat darker in color than the Sicilian oil.
66 Am. Journ. Pharm., 76, p. 185.
67 S. & Co., Rep., April–May, 1905, p. 85.
68 S. & Co., Rep., Oct.–Nov., 1905, p. 36.
69 Pharm. Journ., 75, p. 860.
70 Haensel's Ber., Sept. 1905, p. 9.
71 Journ. prakt. Chem (2) 72, p. 185.
LEGUMINOSAE, GERANIACEAE, RUTACEAE. 21
dis” = 0.8598; an = +53°56'; an of the first 10 p. c. of the distillate
+ 48°42' (boiling point 165°–175°); n p20 = 1.47490.
Estimation. Romeo 72 recommends a new citral assay. It
depends upon the fact that when citral is absorbed by potassium or
sodium sulphite to which has been added sufficient excess of the acid
sulphite for the liquid to remain acid after the absorbtion, the citral
reduces the acidity in the proportion of 3 molecules for each mole-
cule of citral as shown in the following reactions:
H 2Na2 SO3
1. Co H150× -- + 2 H2O = C9H17. (SO3 Na) 2.0H (OH) SOaNa,
\o NaH SOs + 2NaOH.
2. 2NaOH + 2 Na,FISO3 = 2 H2O + 2 Na2SO3.
Dissolve 400 grams of crystalized sodium sulphite in one liter of water and
add sufficient saturated solution of the bisulphite to make 25 c. c. sufficiently
acid to neutralize about 20 c. c. of Seminormal potash. The solution should
be heated on a water bath for 3 hours before determining the acidity.
Weigh out about 5 grims. Of oil and neutralize any free acid with dilute
alkali, using roº olic acid as indicator. To the oil add 25 c. c. of the sulphite
solution, heat for 45 minutes and again determine the acidity. The difference
is the diminution of acidity in terms of N/2 alkali.
152 grims. Of citral are equivalent to 3000 c. c. of a N/1 alkali solution
and 1 c. c. of a N/1 solution is equivalent to 0.95066 grims. The percent.
of citral in the oil can then be determined by substituting in the formula
I) X 5.066
——— = percent
|X
in which D is the diminution in the acidity in terms of c. c. of N/1 alkali
and X is the granus of oil.
Berté.78 has also devised a method of citral assay, as follows:
TO 10 c. c. Of Oil add 50 c c. of a saturated solution of potassium acid
sulphite in an Erlenmeyer flask of about 250 c. c. Close it with a stopper
in which is inserted a glass tube 40–45 c. m. long. Shake the mixture until
emulsified and heat to boiling for 10 minutes. Allow to cool completely,
heat again for 5 minutes, shaking the flask vigorously. Allow to cool and
separate the oil from from the sulphite layer, wash twice with distilled
water and dry with sodium sulphate. Then determine an of the resulting
oil. The difference between the rotation of the original oil and of the terpene
oil taken under the same conditions of temperature will give directly the
quantity of aldehydes according to the following formula:
100 (A–a)
percent. H ——
A
in which A = ap of terpene oil and A = on of original oil.
72 Chem. & Drugg., 67, p. 408.
73 Chem. Ztg., 29, p. 805
22 THE WOLATILE OILS : 1905.
With the method, Berté found pure oil of lemon to have a citral
content of 6.85–7.4 p. c. which is considerably higher than that
ordinarily accepted.
Oil of lemon is official in the following pharmacopoeias:
8->
U. S. Sth ed. Austria, 8th ed. Spain 7th ed.
Citral...................... 4 p. c. 1 *= - - *=
Sp. gr................. ... 0.851–0.855. (25°) 0.858–0.861 (15°) less than 1.
(AD . . . . . . . . . . . . . . . . . . . . . . . . . . + 60° (25°)2 *= a- dextro.8
Solubility............... -* *- 5 vol. Of alcohol + 95 p. c. alc.
ap of first 10 p. c. t
of dist................. differ by 2° from
ap of oil 5 *-*- - *==
197. Oil of Sweet Orange. G.-H...-K., p. 471.
Oil of orange is official in the following pharmacopoeias:
U. S. Sth ed. Austria, 8th ed.
Color........................ light yellow" --sºms
Sp. gr............. • e º e º 'º e º 'º 0.84.2–0.846 (25°) 0.848–0.852 (15°)
C/ſ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . In Ot, below —H 95° 7 -*me
Solubility...... ......... -* - sol. in alcohol,8 becoming cloudy.
199. Oil of Bergamot. G.-H...-K., p. 473.
Vol. Oils: 1904, p. 31.
Adulteration. Schimmel & Co.74 report the frequent adultera-
tion of bergamot Oil with lemon Oil or lemon oil terpenes. These
adulterations can be most easily detected from a linalyl acetate
determination.
Romeo and Moricca 75 claim that adulterations of bergamot oil
can readily be detected by distilling 30 c. c. of oil into fractions of
5 c. c. and determining the rotations of the first two fractions. In
the case of pure oils the rotation of the first fraction is larger than
that of the second, while with adulterated oils the reverse is true.
Oil of bergamot is official in the Spanish pharmacopoeia, 7th ed.
4 S. & Co., Rep., Oct —Nov , 1905, p. 25.
5 S. & Co., Rep., Oct.–Nov., 1905, p. 26.
The method of assay is not reliable. S. & Co. Also, Umney and Bennett.
Much of the commercial Oil Will not meet this requirement. Francis.
2 Should have been + 59° to + 64°. Umney and Bennett.
3 S. & Co. recommend + 58 to +64° (20°).
4. Gives cloudy sol. with 9() p. c. alcohol. S. & Co.
5 I)ifference is sometimes 59 of pure oils. S. & Co.
G Color is yellow to orange-ye low. S. & Co.
7 NOt, below 950 30’ at 20°. S. & Co.
8 1 vol. is soluble in 8–10 vol. 90 p. c. alcohol with turpiditity. S. & Co.
RUTACEAE 23
Color = green or yellowish green 1.
Sp. gr. = 0.86 to 0.882.
a D = dextro.
Solubility =% vol. 85 p. c. alcohol.
203. Oil of Mandarins. G.-H...-K., p. 479.
Source. Mandarin oil is obtained by hand pressure with a thin
sponge from the green peel of Citrus madurensis, Citrus deliciosa and
Citrus bigaradia sinensis. The oil is generally made in November,
1000 mandarins yielding about 400 grams of oil.
Properties. From the examination of 9 pure oils, Berté and
Gulli 76 determined the following constants:
Sp, gr. at 15° = 0.854 to 0.858.
a D = + 67° to + 73°.
Boiling point = 171° to 175° (50 p. c.).
Adulteration. To detect adulterations with limonene, sweet
orange oil, lemon oils, lemon terpenes and turpentine oil, distill off
50 p. c. of the oil and determine the ap of the distillate and residue.
The rotation of the distillate should be 3° higher and the rotation
of the residue 3° lower than that of the original oil.
205. Oil of Neroli. G.-H...-K., p. 480. Vol. Oils: 1904, p. 32.
Schimmel & Co. have examined a number of neroli oils which, as
shown in the table, have a certain regularity in the alteration of the
constants according to the time of production:
Distillat. Of d 15° (ZD In D209 Ester number
May 11 – May 25.................. 0.8764. +2° 37' 1.47303 46.5
“ 26 – “ 30.................. O.8762 —H 4° 1.4724.5 44.0
“ 31 – June 2 ................. 0.8745 + 5° 2' 1.47264 37.1
June 3 – “ 7.................. 0.87.4.1 + 5°30' 1.47 186 38.1
The oils were soluble in 1.2 and more vol. of 80 p. c. alcohol;
separation of paraffin decreases from first to last oil.
Oil of orange flowers is official in the 8th ed. of the Austrian and
in the 7th ed. of the Spanish pharmacopoeias.
Austria. Spain.
Color..................................... colorless or yellow8 colorless, then yellow
Sp. gr................................... 0.870–0.880 (15°) 0.85–0.90 (15°)4
Solubility............................. Sol. in alcohol *E=º mºmºmº
76 Chem. & Drugg., 67, p. 445.
i Expressed oil is brownish yellow ; distilled oil is colorless. S. & Co.
2 Expressed oils O.881–0.886; distilled oils 0,865 to (). 880. S. & Co.
8. Only freshly distilled oil is colorless. S. & Co.
* Should be between 0.87–0.88, S. & Co.
24 THE VoI.ATILE OILs: 1905.
207 a. Lemon Petitgrain Oil.
Litterer 77 has distilled a yellow oil from the leaves and twigs of
Citrus limonum: dis” = 0.8824; an = +21°08'; no 28° = 1,4725.
The oil contains 24 p. c. of citral (8-naphto-cinchoninic acid,
m. p. 197°); 10.5 p. c. of the ester CH3COOC10H17; 8.2 p. c. com-
bined alcohol; 11.2 p. c. of free alcohol; limonene (tetrabromide,
m. p. 104°); geraniol and linalol and probably camphene. -
A sample of oil of lemon leaves, sold under the title of “petit-
grain citronnier,” examined by Umney and Bennett 78 had the follow-
ing properties: Sp. gr. = 0.873; an = +26°; 9.4 p. c. of esters,
38.9 p. c. of alcohols and 29 p. c. of aldehydes principally citral.
207 b. Orange Petitgrain Oil.
The Oil distilled from the leaves and twigs of Citrus aurantium,
Risso., is a clear yellow liquid; d.15° == 0.8603; an = + 56°46’;
In p 20° = 1.472. -
Litterer 79 found the oil to contain 4 p. c. of citral (3-naphto-
cinchoninic acid, m. p. 197°); 4.1 p. c. of the ester CH3COOC10H17;
19.7 p. c. of total alcohol, C10H17OH ; camphene (isoborneol 112°);
limonene (tetrabromide, m. p. 104°); geraniol and probably linalol.
The oil is formed with greater activity in the young organs which
have attained their full development.80 -
207 c. Oil from Fagara Oct andra. -
The oil obtained from Fagara octandra, L., a tree growing in
Mexico, has a bright yellow color and a linalool-like odor; d.15° =
0.922; an = +2°30'; ester number 6.09; soluble in 0.5 vol. of 90
p. c. alcohol, when more than 1.5 vol. are added, cloudiness occurs. 81
OILs OF BURSERACEAE.
209 a. Oil from Heerabol-Myrrh.
Tschirch and Bergmann 82 obtained a thick yellow Oil from
Heerabol-Myrrh which resinified easily. Sp. gr. = 1.046.
77 Bull. Soc. Chim., 33, p. 1081.
78 Pharm. Journ., 5, p. 861.
79 Bull. Soc. Chim , 33, p. 1079. -
80 Roure-Bertrand Fils, Bull., Oct., 1905, p. 28. ,
81 S. & Co., Rep. April–May, 1905, p. 82.
82 Arch. d. Pharm., 243, p. 649.

RUTACEAE, BURSERACEAE. 25
214. Oil of Linaloe. G.-H...-K., p. 492; Vol. Oils: 1904, p. 35.
Schimmel & Co.88 report further on the examination of dextro:ota-
tory linaloe oils. Three oils examined had the following constants:
I. II. III.
Sp. gr............................... ........... ............ O.8816 ().8783 ().8801
CLI) • - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + 6°:3’ + 8° 0' + 2°54'
Acid No.................................................... 1.7 1.4 1.3
Ester No,..... ............................................ 20.0 3.5 3.74.
nd at 20°.......................... . . . . . . . . . . . . . . . . . . . . . . . . 1.4.6.209 1.46 1 49 *
Solubility in 70 p. c. alcohol.................. 1 : 1.6 1 : 2 1 : 1.6
The alcohol part of the oil consists of d-linalool; l-terpineol,
m. p. 35° (phenylurethane, m. p. 82°); nerol (diphenylurethane,
m. p. 51°–53°).
The examination shows that dextro-rotatory linaloe oil — apart.
from the optical rotation — has the same constituents which are
important for the odor, as laevo-rotatory linaloe oil.
OILS OF MELIACEAE.
215. Oil of Cedrela Wood. G.-H...-H., p. 494.
Some oils distilled from cedrela species, according to Schimmel
& Co.,84 had the following constants: *
I. dis? = 0.9134; an = + 15°50'; no 20° = 1.50169; ester
number 0.8; ester number after acetylation 18.7; soluble in 6 to 6.5
vol. of 95 p. c. alcohol.
II. d 15° = 0.9131; a p = + 13°55’; np = 1.50.142; ester number
0.2; ester number after acetylation 16.7; soluble in 6 to 6.5 of 95
p. c. alcohol.
OILS OF THE EU PHORBIACEAE.
218 a. Oil from Croton Echinocarpus.
The bark of Croton echinocarpus, a tree growing in S. America,
yields 0.502 p. c. of a yellow oil, having a cajeput-like odor and
a burning taste. Sp. gr. at 23° C = 0.942. The color of the oil
gradually changes to green.85
OILS OF THE AN ACAR DIACE A.E.
221. Oil of Schinus. G-II.-K., p. 497.
. The phelland rene distilled from Srhinus molle L. with steam
(sp. gr. at 19° = 0.829; ap = + 58°) consists principally of a-phel-
landrene.86
88 S. & Co., Rep., Oct.-Nov. 1905, p. 47.
84 S. & Co., Rep , Oct —Nov., 1905, p. 18.
85 Ber. d. D. Pharm. Ges., 15, p. 190,
86 Chem. Centralbl., 1905, 2, p. 674.
26 THE WOLATILE OILs: 1905.
OILS OF THE MALVACEAE.
224. Oil of Ambrette Seeds. G.-H...-K., p. 501; Vol. Oils: 1904,
p. 35.
According to Nollet,87 the cultivation of Abelmoschus moschatus,
Moench. is carried on at Martinique, West Indies. The plant is an
annual which grows about 6 feet high. The seed is sown in May in
rows, 3 feet apart. After 4 months the harvest commences. Each
single fruit has to be cut off separately and with the greatest care,
as any injury to the plant would be detrimental to the production
of new good fruit.
OILS OF THE DIPTERO CARPACEAE.
227. Oil of Gurjun Balsam. G.-H...-K., p. 503.
A sample of gurjun balsam from the East Indies, which had a
greenish-blue color and a faint fluorescence, was distilled with steam
by Schimmel & Co.88 The oil, obtained at a yield of 60 p. c., had a
yellow color and a balsamic odor. d.15° = 0.9236; an = —97°6’;
no 20° = 1.50326; ester number 0.99; soluble in 9 vol. of 95 p. c.
alcohol.
OILS OF THE MYRTACEAE.
232. Oil of Myrtle. G.-H...-K., p. 507.
An oil of myrtle from Spain had the following properties:
dis? = 0.9406; an = + 23.04°; saponification number 128; saponi-
fication number after acetylation 159; 1 gram is soluble in 0.85
gram of 80 p. c. alcohol.89
The higher boiling fractions of myrtle oil, which have the charac-
teristic myrtle odor, consists, according to Soden and Elze,90 prin-
cipally of esters of a terpene alcohol called myrtenol, C10H18O. It
is a thick colorless liquid, b. p. 220–221° (751 m. m.); d.15° = 0.985;
a d = +49°25'. It is a primary alcohol with one double bond and
yields a phthalic acid ester melting at 116°.
234. Oil of Pimenta. G.-H...-K., p. 509; Vol. Oils: 1904, p. 36.
Pimenta oil is official in the 8th edition of the U. S. Pharma.
copoeia, with the following constants: Colorless, yellow or reddish;
not less than 65 p. c. of eugenol; sp. gr. at 25° = 1.033—1.048
87 Agric... practioue des Pays chauds, p. 126.
8 S. & Co., IRep., Oct.–Nov., 1905, p. 39.
89 Haensel's Ber., Sept. 1905, p. 28.
90 Chem. Ztg., 29, p. 1031.
MALVACEAE, DIPTEROCARPACEAE, MYRTACEAE. 27
(lower limit should be 1.018. S. & Co.); soluble in 2 vol. of 70 p. c.
alcohol and in every proportion in 90 p. c. alcohol.
235 a. Oil of Bay. G.-H...-K., p. 510.
The bay berries, from the Bermuda islands, yield 3.66 p. c. of a
yellowish-brown oil which has an aromatic odor entirely different
from the ordinary bay oil. d.15° = 1.0170; ap = —7°3′; soluble in
1.5 vol. of 70 p. c. alcohol, the solution becoming cloudy when more
than 4 volumes were added.
The oil contains 73 p. c. of eugenol (benzoyl compound. The
non-phenol oil contains l-phellandrene (nitrite, m. p. 103°), but no
myrcene.91
236. Oil of Cloves. G.-H...-K., p. 512; Vol. Oils: 1904, p. 37.
Frankforter and Lando 92 have determined the constants of pure
eugenol, as follows: Boiling point 244.5°C.; sp. gr. at 20° = 1.0689;
np = 1.54437.
To prepare eugenol dibromide, dissolve eugenol in chloroform
at 0° and add bromine very slowly. Subject the mass to steam
distillation and allow the residue to stand, when it will solidify to a
white crystalline mass. The reaction is quantitative.
Oil of cloves has the following pharmacopoeial requirements:
U. S. 8th ed. Spanish 8th ed.
Color............ colorless or light yellow colorless, turning yellow, red or brown
Eugenol....... 80 p. c. e-º- ºm-º.
Sp. gr.......... 1.040—1.060 (25°); 1.04—1.06 (15°):
O'D. . . . . . . . . . . . . . . . . *mºs =ºmsº laevo
Solubility..... 2 vol. 70 p. c. alcohol *-* *-*º-
Eugenol is official in the U. S. and Austrian pharmacopoeias.
238. Oil of Cajeput. G.-H...-K., p. 518; Vol. Oils: 1904, p. 38.
Cajeput oil is official as follows:
* U. S. 8th ed. Austrian 8th ed. Spanish 7th ed.
Color............. colorless or green green colorless or green
Cineol............ 50 p. c.1 *E=ºmº E-mºmºmº.
Sp. gr........... 0.915–0.925 (25°)2 0.920–0.9303 (15°) 0.91—0.954
*D...... ........... not above —2°5 *E=ºmº + O
Solubility ..... 1 vol. 80 p. c. alc. readily sol. in alc. readily sol. in alc.
91 S. & Co., Rep., April-May, 1905, p. 85.
92 Journ. Am. Chem. Soc., 27, p. 641.
94 Journ. Chem. Soc , 87, p. 689.
Oils with 80 p. c. eugenol have d. = 1.083, S. & Co.
Upper limit should be 1.07 (159). S. & Co.
i Method of assay not reliable, S. & Co.
2 Lower limit should be 0.913, S., & Co.
8 Lower limit should be 0 919. S. & Co.
: Should have narrower limits, 0.919–0.930. S. “sº
Pure oils have been noticed with O.D == -–2° 40'. g & Co.
28 THE WOLATILE OILS : 1905.
248 a. Oil from Psidium Guayava.
Altan 95 obtained from Djamboe leaves from Psidium guaya Va a
yellowish-green oil, which contains eugenol. Sp. gr. 1.069; b. p.
237° C.
249. Oil of Eucalyptus globulus. G.-H...-K., p. 549 A
Wol. Oils 1904, p. 39.
Composition. From the higher boiling fractions, Wallach &
Jaeger 96 isolated an alcohol C10H16O, which upon purification by
means of its acid phthalate was found to be l-pinocarvedl. B. p. 92°
(12 m. m.); sp. gr. 0.97.45 at 20°; [a]n in 12.75 p. c. ethereal
solution = —52.45°.
A dult era tion. Bennett 97 reports the adulteration of eucalyp-
tus oils with 15–20 p. c. of castor oil. The oils had normal con-
stants and the adulteration could only be detected by a cineol assay
or examination of the residue after steam distillation.
According to Collins 98 not Ao of the oil sold as Eucalyptus
globulus is from that species. Oils from other species have a more
pleasant odor than that from Eucalyptus globulus which is some-
what nauseating.
Eucalyptus oil and eucalyptol are official in the U. S. 8th ed.
and the Spanish 7th ed.
U. S. Sth ed. Spanish
Oil Eucalyptol Oil Eucalyptol
Sp. gr......... 0.905–0.925 (25°) 0.925 (25°)1 0.90–0.92 (15°)2 0.940 (15°).
B. p............ - 1769—177 o *- 17494
M. p............ *- — 19 *- + 19
Solubility...3 vol. 70 p. c. alc. in every prop. 1 pt. of alc. in every prop.
O'D. . . . . . . . . . . . . . . not Over +10° -*. dextro -*
1 Should be O. 921—0923. . S. & Co.
2 Upper limit should be 0.93. S. & Co.
3 Should be ().928—().9:30 (159). S
4. Should be 1769–1779. S. & Co.
273 a. Oil of Eucalyptus Polybractea.
The leaves of Eucalyptus polybractea, yeld an oil which, according
to Umney & Bennett is practically free from aldehydes and there-
fore has no irritating or disagreeable odor. Sp. gr. 0.929; ap = +0.
Eucalyptol content 79–80 p. c. The species never attains tree form
95 Pharm. Post, 37, p. 713.
96 Chem. Centralbl., 1905, 2, p. 674.
97 Chem. & I) rugg., 66, p. 33.
98 Chem. & Drugg., 67, p. 103.
1 Pharm. Journ., 74, p. 143, 211,
MYRTACEAE. 29
*
and grows luxuriously and should become an important source of
eucalyptus oils. The oil examined may, however, have been a recti-
fied oil.
273 b. Oil of Eucalyptus Consideneana.
The first eucalyptus oil was probably distilled from the leaves of
Eucalyptus consideneana in 1788 by First Asst. Surgeon D. Considen
after whom the species was named. The oil was called a peppermint
oil. 273 c. Oil of Eucalyptus Salmonophloia.
Eucalyptus salmonophloia, F. v. M., is an average forest tree
having a smooth, grey and somewhat purplish, bark of an oily luster,
l:ence its name, Salmon Bark Gum.
The leaves yield 1.44 p. c. of a reddish oil. d.15° = 0.9076;
ap = + 6.3°; saponification number 4.97; soluble in 3.5 vol. of 70
p. c. alcohol. Baker and Smith 8 have identified cineol (47.8 p. c.),
pinene and aromadendral.
273 d. Oil of Eucalyptus Redunca.
The leaves of Eucalyptus redunca, Schauer, commonly called
White Gum, because of its white bark, yields 1.205 p. c. of a reddish
oil with with a decided terpene odor.4 d15°= 0,9097; ap = +13.5°;
saponification number 2.4; no = 1,4720; soluble in 6 vol. of 70 p. c.
alcohol. The oil contained 40 p. c. of cineol, d-pinene and a ses-
Quiterpene.
273 e. Oil of Eucalyptus Salubris.
The leaves of Eucalyptus salubris, F. v. M., called the Gimlet
Gum, because of the twisted character of the outer surface of the
stem, yields 1.391 p. c. of an oil of orange-brown color and a strong
aromadendral odor. d.15° = 0.902; a p = —5.8°; saponification
number 18.88; no = 1.4841; soluble in 1 vol. of 80 p. c. alcohol.5
The oil contained 10 p. c. of eucalyptol; the aldehyde aroma-
dendral to which the laevo rotation of the oil is due; cymene; a
sesqu' terpene; and geranyl acetate. The oil also contains some free
acid due to the ease with which geranyl acetate saponifies.
The aldehyde aromadendral has a sp. gr. at 16° = 0.9576;
np = 1.5141; b. p. 218–219°; ap at 22° = —86.2°. It yields a
2 Chem. & Drugg., 66, p. 220.
3 Pharm. Journ., 75, p. 357.
4 Pharm. Journ., 75, p. 358.
5 Pharm. Journ., 75, p. 859,
30 THE Volatile OILS : 1905.
hydrazone melting at 104°–105°; oxime, m. p. 86°; 8-naphto-
cinchoninic acid, m. p. 24.5°–246°.
273 f. Oil of Eucalyptus Marginata.
Eucalyptus marginata, Sm., is especially valued for its fine tim-
ber of which a large amount is exported.
Baker and Smith 6 obtained 0.243 p. c. of oil from the leaves
which was red in color and had an odor indicating aromadendral.
dis? = 0.9117; ap = —8.5°; no = 1.4946 at 16°; saponification
number 13.12; soluble in 1 vol. of 80 p. c. alcohol.
Another shipment of leaves yielded 0.198 p. c. of oil; d.15°=0.8889;
ap = –10.4° due to larger percent of aromadendral; saponification
number 10.254; soluble in 5 vol. of 80 p. c. alcohol.
The oils contained less than 10 p. c. of cineol; a small amount
of pinene; cymene; a sesquiterpene; and aromadendral.
279. Oil of Backhousia Citriodora. G.-H...-K., p. 538.
An oil distilled in Queensland from Backhousia citriodora was a
greenish-yellow, optically inactive liquid. de1° = 0.8903; no 22°=
1.494. The oil contained 93 p. c. of citral and should become a new
source for citral to compete with the much higher priced lemongrass
Oil. 7
An oil examined by Schimmel & Co. 8 had a yellow color and an
odor like lemongrass oil. d.15° = 0.8972; a p = +0; soluble in 1.8
vol. of 70 p. c. alcohol. The oil contained 95 p. c. of aldehyde,
probably exclusively citral.
282. Oil of Eucalyptus Diversicolor. G.-H...-K., p. 539.
Baker and Smith 9 obtained 0.825 p. c. of a yellow oil from the
leaves of Eucalyptus diversicolor, F. v. M. The oil had a terpene-
like odor and consisted largely of pinene and an ester of acetic acid.
dis” = 0.9145; ap = + 30.1°; saponification number 53.2; no =
1,4747; soluble in 1 vol. of 80 p. c. alcohol.
The oil also contained less than 5 p. c. of cineol but no phel-
land rene.
Pharm, Journ , 75, p. 382.
6
7 Chem. & Drugg., 67, p. 17.
8 S. & Co., Rep., Aºllº 1905, p. 83.
9 g
*
Pharm. Journ., 75, p. 38
MYRTACEAE, UMBELLIFERAE. 31
288. Oil of Eucalyptus Occidentalis. G.-H...-K., p. 540.
The leaves of Eucalyptus occidentalis, Endl., yield 0.954 p. c. of
a red oil. d.15° = 0.9135; ap = + 9.0°; np = 1.4774; saponification
number 2.48; soluble in 1 vol. of 80 p. c. alcohol.
The oil contained 36 p. c. of eucalyptol, d-pinene, aromadendral,
and a sesquiterpene, but no phellandrene. 19
294 a. Oil of Eucalyptus Calophylla.
The leaves of Eucalyptus calophylla, R. Br., commonly called the
Red Gum, yield 0.248 p. c. of an oil which has a dark red color and
a turpentine-like odor. d.15° = 0.8756; an = + 22.9°; saponification
number 10.51; no = 1.4788; insoluble in 10 volumes of 80 p. c.
alcohol.
The oil contains a large amount of d-pinene, cymene, a sesquiter-
pene and traces of eucalyptol. Phelland rene and aro madendral were
absent. 11
294 b. Oil of Eucalyptus Gomphocephala.
From the leaves of Eucalyptus gomphocephala, D. C., Baker and
Smith 12 obtained 0.031 p. c. of a very mobile, reddish oil which had
a rank, unpleasant odor. d.15° = 0.8759; n n = 1.4815; saponifica-
tion number 25.74; insoluble in 10 volumes of 80 p. c. alcohol.
The oil is largely a terpene oil, containing pinelland rene in some
Quantity. Eucalyptol could not be detected.
OILS OF THE UMBELLIFERAE.
296. Oil of Coriander. G.-H...-K., p. 541; Vol. Oils: 1904, p. 40.
According to the U. S. Pharmacopoeia, 8th ed., coriander oil
should be colorless or light yellow; d.25° = 0.863–0.878; an = 7°
to +14°; soluble in 3 vol. 70 p. c. alcohol.
302a. Oil of Arthusa Cynapium.
Power and Tutin 18 obtained 0.015 p. c. of oil from Arthusa
cynapium, L., commonly called fools parsley or the lesser hemlock.
The plants, collected when fruits were fully developed but still green,
were extracted with alcohol and the extract distilled with steam.
The oil had an unpleasant odor, and was colorless at first, rapidly
10 Pharm. Journ., 75, p. 358.
11 Pharm. Journ., 75, p. 356.
12 Pharm. Journ., 75, p. 384.
18 Journ. Soc, Chem. Ind., 24, p. 938.
32 THE WOLATILE OILS : 1905.
turning brown. The aqueous distillate contained a small quantity
of formic acid.
305. Oil of Caraway. G.-H...-K., p. 550; Wol. Oils: 1904, p. 40.
Schimmel & Co.14 have isolated from caraway oil a small quantity
of a base with a narcotic odor which was not examined further;
dihydrocarvone (oxime, m. p. 89°) and dihydrocarvedl.
From a careful study of the chemical behavior of eucarvone,
Wallach 15 gives it the formula:
CH3
|
C
N
« c=0
| |
CH CH2
| |
CH-COCH3)2
Oil of caraway is official in the U. S. P. 8th ed. and carvone in
the Austrian Pharmacopoeia 8th. ed.
|U. S. Austria.
Oil. . Cary One. .
Sp. gr............................. ..... 0.905–0.915 (25°)1 0.960–0.964 (15°) 2
C/I) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + 70° to +80° (25°) &=º-º-º-º:
Solubility........... ................. 3 to 10 vol. 80 p. c. alcohol 2 pts. dil. alcohol
B. p....................................... 2299—230°
1 This is the sp. gr. at 15°; it should be 0.899–0.909. S. & Co.
2 Should be 0.963—0.966. S. & Co.
3.09. Oil of Fennel. G.-H...-K., p. 563; Vol. Oils: 1904, p. 41.
Semmler 16 recommends for fenchone the formula
H20––CH-C=(CH3)2
g º
hº-º-º-o
(SH3
as best explaining the oxidation of fenchone to acids.
The new pharmacopoeial requirements for oil of fennel are:.
f
U. S. 8th ed. Austrian 8th ed.
Sp. gr............................................ 0.953–0.973 (25°) 0.965–0.975 (15°)
Solidif. pt...................................... –– 50 * + 5°
Solubility...................................... 10 vol. 80 p. c. alcohol 1 vol. of alcohol
* Should be not below —H 4°. S. & Co.
14. S. & Co., Rep., April–May, 1905, p. 20.
15 Ann., 339, p. 94.
16 Chem. Ztg., 29, p. 1318,
MYRTACEAE, ERICACEAE. 33
312. Oil of Water Fennel. G.-H...-K., p. 568.
In the preparation of phellandrene nitrite in which a yield of 25
p. c. is rarely obtained, Wallach 17 has shown that much nitro-3-
phellandrene is formed. The relation of these compounds is shown
by the following formulas:
gºo. gºo. Chino,
|
CNO C C
/ N / N / N
H2O/ NCH He/ NCH H2O/ NCH
| | | || 0 || |
H2CN / CH H2ON / (; H H2CN / CH
N / N / N /
CH CH CH
| | i .
CH(CH3)2 CH (CH3)2 CH(CH3)2
g-phellandrene nitrite. Nitro-3-phelland rene.
334 a. Oil of Eryngium Campestre.
The fresh herb of Eryngium campestre L. yields 0.088 p. c. of a
faint yellow oil, having a pleasant odor. dis?= 0.9043; ap = —5°42';
np 20° = 1.48518; ester number 10.47; insoluble in 10 volumes of
80 p. c. alcohol; soluble in 1 vol. of 90 p. c. alcohol.18
OILS OF THE ERICACEAE.
337. Oil of Wintergreen. G.-H...-K., p. 585.
Ziegelmann 19 has determined by a colorimetrie estimation, that
the greatest yield of oil is obtained by previous maceration of the
leaves at room temperature for 24 hours. From the estimation a
yield of 1.58 p. c. was obtained while in actual distillation on a
larger scale only 0.633 p. c. resulted. d.15° = 1.1559; soluble in 6
volumes of 70 p.e. alcohol. The crude oil contained 90.959 p. c. of
methyl salicylate.
Oil of gaultheria and methyl salicylate are both official in the
U. S. P. 8th ed.
()il of Gaul theria. Methyl salicylate.
Color............................... Colorless or almost colorless Colorless
Sp. gr.............................. 0.172–1.180 (25°) 1.180—1.185 (15°) 2
“D.................. .................. — 1o + ()
B. p.................... .....…... 218–221° 219–221°
1 Oils are colored red from traces Of iron. S. & Co.
Oils are usualiy red. Umney and Bennett.
2 Lower limit should be 1 177. S. & Co.
17 Ann., 340, p. 1
18 S. & Co., Rep., Oct.–Nov. 1905, p. 73.
19 Pharm. Rev., 23, p. 84,
34 THE WOLATILE OILS : 1905.
OILS OF THE LABIATA.E.
346. Oil of Rosemary. G.-H.-K., p. 594.
An oil imported from Tunis, which was distilled not only from
Rosmarinus officinalis L., but also from other plants had the follow-
ing properties: 20 -
dis? = 0.9171; ap = +2° 17'; ap of the first 10 p. c. of the
distillate —2°24'; soluble in 1 and more volumes of 80 p. c. alcohol.
Oil of rosemary has the following pharmacopoeial requirements:
U. S. 8th ed. Austria, 8th ed. Spain 7th ed.
Sp. gr................ 0.894–0.912 (25°) 0.900–0.920 (15°) 0.88–091 (15°) 1
*D ..................... not over +15° - laevo 2
Bornyl acetate.. 5 p. c. +- -
Total borneol... 15 p. c.8 - - -
Solubility.......... 2–10 vol. 80 p. c. alc. sol. in alcohol sol. in 85 p. c. alc.
1 Should be 0.89 – 0.92. S. & Co.
2 Should be dextro. S. & Co.
3 5 p. c. of ester and 15 p. c. of total borneol are too high. S. & Co.
347. Oil of Lavender. G.-H...-K., p. 600.
Schimmel & Co.21 have determined the effect of the following
common adulterants on lavender oil.
Turpen tine oil lowers specific gravity and solubility; the
rotation is raised by laevo French turpentine oil and lowered by
the dextro-rotatory American oil.
Spike oil increases the sp. gr. and lowers the rotation, but does
not affect the solubility.
Spanish la Ven der oil behaves like spike oil but has a less
marked influence on the rotation.
Rose m a rºy Oil also causes similar alterations as spike oil but
renders the oil less soluble.
The ethyl ester of succinic acid is also used to mask the admix-
ture of the above adulterants by raising the ester content.
Oil of lavender is official as shown in the following table:
U. S. 8th ed. Austr, a 8th ed. Spain 7th ed.
Sp. gr............ 0.880–0.892 (25°)4 0.885–0.895 (15°) 0.87–0.94 (15°) 5
Solubility......3 vol. of 70 p. c. ale, readily sol. in alc. sol. in 85 p c. alc.
"I,.................. -- *- laevo.
4 I, Ower limit should be 0.875. S. & Co.
5 Should be 0.882–().895 (159). S. & Co.
30 S. & Co., Rep., Oct.–Nov., 1905, p. 61.
21 S. & Co., Rep , April–May, 1905, p. 52.
LABIATAE. 35
349. Oil of Lavandula Stoechas. G.-H...-K., p. 611.
Schimmel & Co. 22 obtained 0.755 p. c. of oil from the dried
blossoms of La Vandula Stoechas L. The oil had a yellow-brown
color and a strong camphor-like odor. d.15°= 0.9620; ap = +35°30';
mp = 1.47909; acid number 5.16; ester number 13.1; soluble in 2
volumes of 20 p. c. alcohol.
The oil contained d-camphor, m. p. 175° (oxime, m. p. 117° to
118°).
353 a. Oil of Nepeta.
Umney and Bennett 28 have examined an oil of Nepeta from
Sicily whose exact botanical origin was unknown. It had sp. gr. =
0.927; ap = + 12°; soluble in 2 volumes of 70 p. c. alcohol. The
oil contained 22.2 p. c. of alcohols calculated as menthol, and 2.3
p. c. of ester calculated as the menthyl acetate.
354. Oil of Sage. G.-H...-K., p. 612.
A sample of sage oil which had been distilled from plants grown
on Mount Carmel (Palestine) had the following properties:
dis” = 0.9175; an — —9°35'; no 20° = 1.46734; ester number
7.3; insoluble in 10 volumes of 70 p. c. alcohol; soluble in 1 vol.
of 80 p. c. alcohol. 24
254 a., Oil of Salvia Grandiflora.
Wallach 25 examined the oil from Salvia grandiflora for the pur-
pose of producing l-a-thujone, but contrary to ordinary sage oil, it
contained no trace of thujone.
The oil contained l-pinene, cineol, l-camphor, and a hydrocorbon
which gives a nitrite melting at 85–86°.
355. Oil of Salvia Sclarea. G.-H...-K., p. 62.
The fresh blossoms and stems of Slavea Sclarea L., muscatel sage,
grown in Miltitz, yield on distillation 0.117 p. c. of a bright olive-
green oil with a peculiar odor. d.15° = 0,9209; a p = —23° 38';
no 20° = 1.477 24; acid number 0.9; ester number 153.0; ester num-
ber after acetylation 153.9; soluble in 1.5 vol. 80 p. c. alcohol with
slight opalescene, from which solution paraffin gradually separates. 26
22 S. & Co., Rept., Oct.–Nov., 1905, p. 40.
28 Pharm. Journ., 75, p. 861.
24 S. & Co., Rep., Oct.-Nov., 1905, p. 62.
25 Nachr. k. Ges. Wiss., Goett., 1905, p. 1.
26 S. & Co., Rep., Oct.–Nov. 1905, p. 62.
36 THE WOLATILE OILS : 1905.
259 a. Field Balm Oil.
The oil of field-balm, Melissa calamintha L., is a faintly yellow
liquid having a peculiar pleasant aromatic odor. dis? = 0.8771;
ap = –16°57'; no 20° = 1.49110; acid number 0; ester number 8.3;
ester number after acetylation 38.95; insoluble in 10 volumes of 90
p. c. alcohol. 27
360. Oil of Pennyroyal. G.-H...-K., p. 617.
A highly rectified oil of pennyroyal, obtained from herb growing
wild in Sicily, and examined by Umney and Bennett 28 had the
following properties: dis? = 0.927; ap = + 35°; 75 p. c. of pulegone
by distillation; soluble in 2 vol. of 70 p. c. alcohol.
The limits of the U. S. P. 8th ed. are: Sp. gr. at 25° = 0.925
to 0.935; ap = + 18 to +22°; soluble in 2 vol. of 70 p. c. alcohol.
According to Haller and Martine 29 pulegone may be reduced by
passing it over reduced nickel at 150°C. The product resembles
peppermint oil and probably consists of isomeric menthols.
367. Oil of Cretian Origanum. G.-H...-K., p. 622.
A sample of origanum oil from Sicily, which had probably been
distilled from Origanum creticum, had the following properties:
dis? = 0.920; an = slightly iaevo; soluble in 2 vol. of 80 p. c.
alcohol. The oil contained 44 p. c. of phenols consisting principally
of cal’vacrol. 80
368. Oil of Thyme. G.-H...-K., p. 623.
Schimmel & Co. report the adulteration of so-called “white”
thyme oil with camphor oil. The colorless thyme oils of commerce
are in most cases adulterated. 81
By reducing thymol, Brunel 8° obtained a compound which he
called a-thymomenthol. It has a boiling point of 215° C.; m. p.
— 5° C.
The 8-compound is the thymomenthol generated from the esters
of the a-compound. It crystallizes in long needles, m. p. 17°, which
have the odor and appearance of menthol.
Both of the hexahydrothymols yield upon oxidation thymo-
27 S. & Co., Rep., Oct.–Nov., 1905, p. 34.
28 Pharm. Journ., 75, p. 860.
29 Fr. Pat., H50, 893.
30 Pharm. Journ., 75, p. 860.
31 S. & Co , Rep., Oct.–Nov., 1905, p. 67.
32 Compt. rend., 140, p. 252, 792.
LABIATAE. 37
amy
menthone, C10H18O. This is a colorless liquid having a similar taste
and odor as natural menthone.
Oil of thyme is official in the U. S. and Spanish pharmacopoeias,
1905.
U. S. 8th ed. Spanish 7th ed.
Color................................. co Orless 1 colorless or yellow
Sp. gr.............. '• • - - - - - - - - - - - - - - - 0.900–0.930 (25°)2 ().89 3
“D...................................... not above —3°4 laevo
Solubility.......................... 1–2 vol. 80 p. c. alcohol 1 vol. 85 p. c. alcohol
Phenols............................. 20 p. c. *
1 Gradually becomes red. S. & Co.
2 LO wer limit should be 0.894. S. & Co.
3 This is the lower limit. S. & Co.
4 Oils are sometimes dextro. S. & Co
372. Oil of Peppermint. G.-H...-K., p. 630.
Three samples of French peppermint oil had the following con-
Stants:
I. • II. III.
Sp. gr. at 15°........... 0.92.49 . 0.910S 0.912
“D.............................. — 5°20' — 1 7°46’ – 35° 18'
Menthol ester........... 9.95 p. c. 10.32 p. c. 20.81 p. c.
Total menthol.......... 45.75 p. c. 50.82 p. c. 69.26 p. c.
Solubility.................. Insol. in 10 vol. of Insol. in 10 vol. of Sol. in 35 vol.
70 p. c. alc. Sol. 70 p. e. alc. Sol. of 70 p. c.
in 1.1 vol. Of 80 in 1.2 vol. Of 80 alcohol.
p. c. alc. becom- p. c. alc. becom-
ing cloudy with ing cloudy with
3 vol. 4 vol.
The differences in the 3 oils are said to be due to the varying
degrees of ripeness of the plants. 88
Sicilan Peppermint Oil.
Experiments are being made in the cultivation of peppermint in
Sicily. Three oils examined by Umney' and Bennett,84 had the
following properties:
- II. III.
July, 1904. Dec., 1904. July, 1905.
Yield......................... 0.4 p. c. 0.15 p. c. *-
dis’........................... 0.908 ().920 0.906
(MI) • - - - - - - - - - - - - - - - - - - - - - - - - - - - - - — 1.4° — 23° — 21°
Total menthol.......... 40.0 p. c. 70.5 p. c. 41.6 p. c.
Free menthol............ 36.4 p. c. 47.8 p. c. 36.9 p. c.
Esters....................... 4.8 p. c. 29.4 p. c. 6.0 p. c.
Solubility.................. 4 vol. 70 p. c. alc. 2 vol. of 80 p. c. 3 vol. 70 p. c.
38 S. & Co., Rep., April–May, 1905, p. 62.
84 Chem. & Drugg., 66, p. 945.
38 THE WOILATILE OILs: , 1905.
Oils No. I and III were distilled when plant was in full bloom and
No. II from second growth in the fall when there was no indication
of buds. *
Oil of peppermint is official as follows:
U. S. 8th ed. Austria, 8th ed. Spain 7th ed.
Color................. colorless 1 colorless or yellow colorless or yellow
Sp. gr............... 0.894–0.914 (25°) 0.90–0.910 (15°) 0.89–0.92 (15°)
a”25°................. —25 to —33°2 *- laevo
Solubility.......... 4 vol. 70 p. c. alc. 4–5 pts, dil. alc. readily sol. in alc.
Ester................. 8 p. c. 8 --- **º-º-º-º-º:
Total ment hol. 50 p. c. 4-mºmº *Eº
1 Oils are often yellow. S. & Co
2 The U. S., P. requirements do not exactly fit Wayne Co. N. Y. oil or the
western Oils. S. & Co.
3 Ester content is too high. S. & Co.
378. Oil of Patchouly. G.-H...-K., p. 656.
Preparation. According to Senešº the collection of the leaves
in Java, where the plants of Pogostemon patchouli are culti-
vated, begins as soon as the plants are 15 cm. high and the collect-
ing is repeated every six months.
Properties. An oil from Perak (Malay States) had a dark
yellow color; d.15° == 0.9525; an = —43°31'; no = 1.5063; soluble
in 7.4 volume of 90 p. c. alcohol.86
Jong 87 has examined the oils from three varieties of patchouli
growing in the botanical gardens at Buitenzorg.
I. Patchouli fleurissant.
II. ( & de Singapour.
III. & 6 de Java. g
I. II. III.
d25°.................................................. O.922 (1.949 0.929
[a]d 25°............................................. —16°10' —51°24' –42°48'
Sol. in 90 p. c. alc.......................... 1 : 10 1 : 6 1 : 0.75
Boiling points:
–250°........................... 17 p c. 2 p. c. 10 p. c.
250°–270°........................... 50 p c. 60 p. c. 70 p. c.
270°–280°........................... 16 p. c. 20 p. c. 8 p. c.
280°–300°........................... 10 p. c. 10 p. c. * 6 p. c.
Composition. Jong isolated a sesquiterpene, b. p. 260–263°;
ap 25° = –1 ; sp. gr. = 0.915, which he calls dilemene.
35 Journ. d’agn. trop., 5, p. 369.
36 Bull. Imp. Inst., 3, p. 226.
37 Rev. trav. chiv. Pays-Bas., 24, p. 309.
LABIATAE. 39
Schimmel & Co.88 have isolated two bases from patchouli oil,
one of which, b. p. 135°–140° (3–4 m. m.) yields a hydrochloride
melting at 147.5°–148.5°. The formula for the platinum double
salt was found to be (C14H23NO.HCl)2PtCl4.
380. Oil of Sweet Basil. G.-H...-K., p. 659.
Charabot and Hebert 89 have determined that by suppressing the
inflorescences, the weight of oil produced by each plant is almost
doubled. The weight of the plant has increased an amount equal to
39 percent of its normal weight, and the weight of the oil has in-
creased an amount equal to 82 p. c. of the normal weight of oil.
The analysis of the oil shows that the work of fertilisation and
fructification entails a consumption of odorous products or at least
of material capable of contributing directly to their synthesis.
From another series of experiments Charabot & Lalone 40 showed
that when shaded from light, the plant is able to consume the
essential oil which it contains and chiefly the terpene compounds.
The results show that the odorous compounds are not, as is com-
monly supposed, excretion products no longer utilisable.
During the period which precedes the appearances of the first in-
florescences, the green parts of the plant contain a comparatively
readily soluble oil which is poor in methyl chavicol, but rich in
terpene compounds. The oil from the first inflorescences in less
soluble and richer in methyl cha vicol.
The leaves of Ocimum basilicum, L, yield 0.37 p. e. of a hydro-
carbon Ocimene, C10H16. This hydrocarbon and the hydrocarbon
myrcene yield upon reduction the same hydrocarbon C10H1s which
has two double bonds and the following constants: b. p. 166–168°
(761 mm ); drs” = 0.779; no 17° = 1.451. It yields a tetrabromide,
melting at 88°. Enklaar 41 shows the relation of these three com-
pounds by means of the following formulas:
88 S. & Co. Rep., April–May, 1905, p. 60.
39 Bull. Rour - Bertrand Fils, Oct. 1905, p. 10.
40 Bull, Roure-Bertrand Fils, May, 1905, p. 7, 13.
41 Inaug. Diss. Utrecht, 1905,
40 THE WOLATILE OILS : 1905.
CH3 CH2—0H CH3 CH2—CH2
>C=CH/ }c—Hs XH=CH* >C=H,
..CH3 CH2=CH CHS CH=CH
Ocimene. Myrcene.
CH3 CH2—CH2
\r-cºrr’ N
2C=CH 20–CHA
CH3 CH3–0H
Dihydro derivative.
OILS OF THE CAPRIFOLIACEAE.
388. Oil of Elder Blossoms. G.-H...-K., p. 663.
A glucoside yielding benzaldehyde has been discovered by Bour-
Quelot and Danjon 42 in the leaves, blossoms and fruit of Sambucus
Imigra, L.
OILS OF THE COMPOSITAE.
396. Oil of Erigeron (Fleabane).
Itabak 48 obtained 0.66 p. c. of a light yellow oil which had a
peculiar odor, like caraway, from the fresh herb of Erigeron cana-
densis, L., and 0.26 p. c. from the dried herb. The properties of the
two oils are recorded in the following table:
Oil from fresh herb. Oil from dried herb.
d22°...... … … ............ ....................... 0.86 14 0.81; 10
"D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................... —H 670 16’ + 76° 37'
Acid number........................ .‘. . . . . . . . . . . . . . O O
Ester number............. ........................ 10S 52
Saponification number........................ 108 52
Acetylization number......................... 108 86
Aldehyde, C10H18O.............................. 0.77 p. c. 0.44 p. c.
400 a. Oil of Inula graveolens.
Inula graveolens, L. Desf., which grows in the Mediterranean
countries, yields upon steam distillation a brown oil with a green
fluorescence. d.15° = 0.9754; ap = —36°40'; acid number 8. 15; ester
42 Journ. de Pharm. et VI. 22, p. 154.
43 Pharm. l{eview, 23, p. 81.
COMPOSITAE. 41
number 161.3; ester number after acetylation 239.38; soluble in 3
to 3.5 volumes of 70 p. c. alcohol, with separation of paraffin. The
oil probably contains bornyl acetate. 44
406. Oil of Achillea Nobilis. G.-H...-K., p. 675.
The oil from the flowers of Achillea mobilis, L., is a greenish-
yellow liquid which has a strong milfoil and camphor-like odor and
a bitter taste. d.15° = 0.9353; an = —20.82° in a 20.82° in a 200
m. m. tube. The oil contains 18.2 p. c. of ester C10H17O.COCHa;
13.1 p. c. of free alcohol; camphene (isoborneol 210°); borneol
(phenylurethane, m. p. 104°–105°).45
413 a. Oil of Tanacetum Boreale.
The fresh herb of Tanacetum boreale, Fisch., yields 0.117 p. c.
of a green-brown oil which has a strong thujone odor. dis?- 0.9603;
np 20° = 1.49167; acid number 30.47; ester number 40.55; soluble
in 2 volumes of 80 p. c. alcohol, paraffin separating when more
solvent is added.46
421 a. Oil of Artemisia Annua.
From the green cultivated herb of Artemisia annua, L., Schimmel
& Co. 47 obtained 0.29 p. c. of a lemon-yellow oil which had a
pleasant refreshing odor. dipº = 0.0942; ap = –1°18’; acid number
3.8. ; ester number after acetylation 44.5; soluble in 1.5 vol. of 80
p. c. alcohol from which paraffin separated upon further addition of
alcohol.
421b. Oil of Artemisia frigida.
Artemisia frigidia, Willd., commonly called wild sage or sage
brush, is a weed growing abundantly in the western part of the
United States. From the fresh herb, Rabak 48 obtained 0.41 p. c.
of a light greenish oil having a cineol odor. From the dried herb
only 0.07 p. c. of a dark oil was obtained. The aqueous distillate
yielded 25 grams of a dark oil when extracted with petroleum ether.
The constants of the three oils are as follows:
44. S. & Co., Rep., April–May, 1905, p. 82.
45 Arch. d. Pharm., 243, p. 288.
46 S. & Co., Rep., Oct.–Nov., 1905, p. 66
47 S. & Co. itep. April–May, 1905, p. 85,
48 Pharm. Itev., 28, p. 128.
42 e THE WOLATILE OILS : 1905.
Oil from fresh herb. Oil from dry herb. Oil from aqueous dist.
Sp. gr. at 22°............ 0.927 0.930 0.916
*D............................... –24°48' *=== 8-ºº-º-º-º:
Acid number.............. 1.2 4.7 5.3
Ester number............ 31.8 40.0 25.0
Saponification number 33.0 44.7 30.3
421 c. Oil of Artemisia leudoviciana.
The entire herb of Artemisia leudoviciana, Nutt., the western
mug wort, yields according to Rabak 0.38 p. c. of a greenish-yellow
oil which had a strong aromatic odor. dz2° = 0.929; ap = –16°14';
acid number 4; ester number 10; saponification number 14.49
421 d. Oil of Artemisia. Caudata.
The fresh herb of Artemisia caudata, Michx., wild wormwood,
yields according to Rabakš0 0.24 p. c. of a yellow oil which had a
very sweet odor suggesting anethol. dz2°= 0.920; a p = 12° 30”;
acid number 0; ester number 17; saponification number 17.
428 a. Oil of Grindelia Robusta.
Power and Tutin 51 obtained 0.068 p. c. of a bright yellow oil
from Grindelia robusta. The aqueous distillate contained formic and
butyric acids.
49 Pharm. Rev., 23, p. 128.
50 Pharm. Rev., 23, p. 128.
5i Proc. Am. Pharm. Ass., 53, p. 149.
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Progress in Alkaloidal Chemistry
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By H. M. GORDIN.
MILWAUKEE,
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Progress in Alkaloidal Chemistry
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By H. M. CORDIN.
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Aconitine.
After an exhaustive historical review of the chemistry of aconitine
H. Schulze gives the results of his own experiments on aconitine and
aconine obtained from Aconitum Napellus. Freund and his callabo-
rators were the first to show that aconitine is acetylbenzoylaconine
and that by hydrolysis it breaks up successively into picraconitine
(benzoylaconine), and then into acetic acid, benzoic acid and aconine.
It was also established that besides two OH groups in which the
H atoms are replaced by an acetyl and a benzoyl group respectively
aconitine also contains a number of free OH groups and 4 CH3O
groups. By analyses of the free base and its hydrobromide and
aurichloride the author shows that of the various formulas proposed
for aconitine the correct one is that given by Freund, i. e. CaAH47NO11.
This formula is also supported by analyses of aconine, methylpicra-
comitine and ethylpicraconitine.
The hydrobromide of aconitine the author obtained in two forms:
one crystallizing with two and a half molecules of water of crystal-
lization, the other crystallizing with 4 molecule of water of crystalli-
zation. The former is identical with the salt previously described by
Jürgens. º
Of the different chloraurates of aconitine the author prepared the
a-compound and found it to contain 3 molecules of water of crystal-
lization which is in accord with Freund's statement (according to
Dunstan the salt contains no water of crystallization).
The hydrolysis of aconitine is best accomplished by heating it in
an autoclave under a pressure of six to seven atmospheres at 160°
to 170°. The yield is about 85 per cent. of theory in the form of
aconine hydrochloride.
Neither aconine itself, C25H8oNO9 or C25II41NO9, nor its sulphate
could be obtained in crystalline form, but the hydrochloride and the
hydrobromide of aconine are crystalline.
2
The author corroborates the statement of Freund about the
presence of 4 methoxyl groups in aconine but finds that the base
also contains a methylimide group from which the CH3 group splits
off very difficultly.
Nitrous acid either does not act at all on aconine or oxidizes it,
but no nitrosamine is formed. Hence aconine must be a tertiary
base. Nevertheless aconine does not combine with alkyl iodides, nor
does it form an aminoxide when treated with hydrogen peroxide.
(See Freund, Ber. 37, 1946.)
As aconine does not react with hydroxylamine or phenylhydrazine
it is neither a ketone nor an aldehyde. Hence of the 9 oxygen atoms
of aconine 4 are in the form of methoxyl groups, the other five in
the form of OH groups. As aconine does not form methyl ethers
when 'treated with methylsulphate the OH groups must all have an
alcoholic character. Of these five OH groups only four are replace-
able by acetyl groups. That the fifth oxygen atom also belongs to
an OH group is shown by the formation of triacetylaconitine when
aconitine is treated with acetyl chloride. This triacetylaconitine was
found to be identical not only isomeric (compare Dunstan, J. Chem.
Soc. '67, 459) with tetracetylpicraconitine obtained by acetylizing
picraconitine. As aconitine is acetylbenzoylaconine and picraconitine
is benzoylaconine, aconine itself must contain 5 OH groups.
When aconitine is heated with alcohols to 120–130° the acetyl
group is replaced by an alkyl group
Cai Hat NO.11 + CH3.OH = Cash4+NO10 + CHA.CO2H
Aconitine. Methylpic raconitinc.
When methylpicraconitine is heated with a large excess of water
to 150–160° for 24 hours it is hydrolyzed to aconine, methyl alcohol
and benzoic acid g
Ca3H47NO.10 + 2 H2O = C25H41NO9 - CH3.OH + Co. Hs CO2H
The hydrolysis of methylpicraconitine being effected with greater
difficulty than that of alconitine the former must be more stable
than the latter. w
That neither aconitine, aconine nor tetracetylaconine contain a
double binding is shown by their stability towards bromine and
potassium permanganate in presence of sulphuric acid (Willstätter,
Ber , 28, 2279; 37, 2353). In alkaline solution potassium perman-
ganate acts enegetically upon aconine forming acetic aldehyde to-
s
3
gether with an amorphous substance of alkaloidal character. Chromic
acid oxidizes aconine to acetic aldehyde, methylaconine, a substance
having basic and one having both basic and acid properties. The
substance of purely basic character was obtained as a crystalline
hydrochloride melting at 213° and corresponding to the formula,
C24 Hä7NOs. HC].3H2O or C28H35NO3.HCl.3H2O. The base underlying
this salt was temporarily named Ia. It seems to be formed according
to following equation :-
C25H41NO9 + 202 = CO2 + 3 H2O + C24 H35NOg
As the new base was found to contain only 3 methoxyl groups while
aconine contains 4 of these groups the carbon dioxide must come
from one of the CH3O groups. Unlike aconine the new base is un-
stable towards potassium. permanganate.
The aconitine was prepared by the following method. The coarsely
powdered aconite tubers were extracted with alcohol, the solvent
distilled off under reduced pressure, the residue taken up with water
and filtered off from fatty and resinous substances. From the
aqueous solution most of the aconitine was precipitated by means
of sodium carbonate and purified by passing through the crystalline
hydrobromide. Both from the agueous mother liquors and the fatty
and resinous substances additional quantities of aconitine were ob-
tained. The aconitine obtained by this method was crystalline,
melted at 197—198° and was identical in every respect with Merck’s
crystalline aconitine from Aconitum napellus. A molecular weight
determination was made by titration using iodoeosine as indicator.
A comparison of the crystalline form of this aconitine prepared from
German aconite root with the crystalline form of English aconitine
showed that contrary to the statement of Dunstan (J. Chem. Soc. 87,
1650) the two aconitines are identical. (Arch. Pharm., 1906, 136.)
According to N. Monti the color reaction obtained by evaporat-
ing aconitine with sulphuric or phosphoric acid is due not to the
alkaloid itself but to impurities which generally accompany it.
Wenzel’s reagent (potassium permanganate and concentrated sul-
phuric acid) is also not characteristic of aconitine as the reagent
reacts in the same way with many other alkaloids. The same is true
of Pinerva’s reaction (Gazz, chim ital., 1905, 429). A good reaction
for the identification of aconitine consists in moistening the alkaloid
with sulphuric acid, then adding a small crystal of resorcinol and
4.
warming the mixture on a water bath. In presence of aconitine a
reddish-yellow color is developed which slowly changes to reddish-
violet. The color is stable for a long time if the mixture be kept in
a desiccator. (Gazz. chim. ital., 1906, 477.)
Alkaloids.
Amé Pictet proposes the following hypotheses for the formation
of alkaloids containing a pyrrol ring, or a pyridine ring, or a combin-
ation of these two rings. The pyrrol ring is supposed to come from
the decomposition of albumins which when hydrolyzed always yield
a-pyrrolidine carboxylic acid as one of the products. This would
explain the presence of an a-pyrrol ring in nicotine, hygrine, cocaine,
atropine, etc. As to the pyridine ring, it is supposed to be formed
from the pyrrol ring by the action of formic aldehyde which accord-
ing to Bayer and Bach is formed in the leaves of plants as the first
product of assimilation of the carbon dioxide. That pyrrol deri-
vatives frequently change to pyridine compounds has been observed
repeatedly. In the same way the quinoline group of alkaloids might
be formed from the indol group of the albumins and the isoquinoline
group of alkaloids from the isoindol ring which according to Küster
exists in chlorophyl. The fact that no other alkyl but methyl has
ever been found in vegetable substances can also be explained by
assuming that the formic aldehyde acts as a methylating agent.
This is in accord with Eschweiler’s observation according to which
methylamines are formed by the action of formic aldehyde on
ammonia.
30H2O + 2NH3 = 20 H3. NH2 + CO2 + H2O
According to the author a similar methylating action is exercised
by formic aldehyde in presence of phenols. This would explain the
presence of N.CH3 and O.CH3 groups in vegetable products. The
author intends to investigate the action of formic aldehyde upon
pyrrol. Arch. Pharm., 1906, 389.
M. Herder has made some experiments upon the microchemical
detection and localization of alkaloids in plants. It was found that
barium and caesium mercuric iodide are more delicate for the detec-
tion of alkaloids than potassium mercurie iodide and that, if the
reactions are carried out in a 30 per cent, solution of chloral hydrate
instead of in water the precipitates produced by these reagents are
either crystalline from the start or very soon become so.
5
Of the commonly occuring organic acids oxalic acid is the only
one which produces a precipitate with barium mercuric cyanide.
The author gives results of examinations of different organs of
Fibraurea chloroleuca, Hydrastis cana densis, Strychnos nux vomica,
Cinchona ledgeriana and Conium maculatum.
(Arch. Pharm., 1906, 120.)
Alkaloidal Double Salts.
A. Christensen has investigated some double salts of alkaloidal
hydrochlorides and hydrobromides with the higher chlorides and
bromides of some metals. While most of these compounds are un-
stable owing to the action of the active halogen on the alkaloid
there are a few that possess sufficient stability for analysis. Among
the latter might be mentioned the following compounds. a-Cinchoni-
dine bibromide hydrochloride lead tetrachloride, C19H22 Br2N2O.-
2HCl, PbCl4.2H2O, was prepared by slowly adding lead tetrachloride
to a solution of a-cinchonidinedibromide in hydrochloric acid (8%).
The compound forms slightly yellowish columus. The corresponding
8-cinchonidine compound could not be obtained in pure condition.
Of the corresponding cinchonine compounds the a-compound was
obtained in yellow needles while the 3-compound could not be ob-
tained pure. The estimation of chlorine in these compounds was
carried out by Bunsen’s method (Ann. 88, 365), that of the lead by
precipitating the lead as a sulphate in presence of alcohol. A com-
pound of lead tetrabromide with the hydrobromide of 8-cinchonidine-
dibromide, C19H22ON2Brz.2H Br. Pb Brà, was also made but it could
not be obtained free from perbromide.
Manganic compounds were prepared by adding strong hydro-
chloric acid to a solution of the alkaloidal acetate and manganic
acetate in glacial acetic acid. In this way were obtained the follow-
ing compounds. a-Cinchonidinedibromide hydrochloride manganic
chloride, C19H22ON2 Br2.2HCl, MnOls.2H2O, forms green crystals, is
decomposed by water and is converted into periodide upon addition
of potassium iodide and hydrochloric acid. The compound loses
chlorine very easily particularly in sunlight. The corresponding
8-cinchonidine compound resembles the a-compound but contains
only one molecule of water of crystallization. The corresponding
cinchonine compounds are not very stable.
(3
According to the author most alkaloids form double compounds
with ferric chloride in presence of much hydrochloric acid.
Quinine hydrochloride ferric chloride, C20H24O2N2.2HCl. FeCl2.H2O,
was prepared by adding successively fer, ic chloride and hydrochloric
acid to a solution of quinine hydrochloride. The compound forms
a yellow crystalline powder easily soluble in water. In the same way
were prepared the corresponding cinchonine salt, C19H22ON2.2HCl.-
FeCla. H2O, and the cinchonidine salt. The latter contains two mole-
cules of water of crystallization.
a-Cinchonidinedibromide hydrochloride ferric chloride, C19H22-
N2O. Brz.2HCl. FeCl3.2H2O, was obtained in the form of yellow needles
by treating a solution of the alkaloid in dilute acetic acid with ferric
chloride and hydrochloric acid. In the same way were obtained the
corresponding strychnine salt, C21H22N2O2.HCl. FeCla, in form of
brown yellow twin crystals, the brucine salt, C22H26N2O4. IICl.-
FeCl3.2H2O, and the cocaine salt, C17H21 NO4.HCl. FeCls. The cor-
responding morphine salt, C17H19NO3.HCl. FeCla. H2O, was obtained
in form of brown needles by passing hydrochloric acid gas into a
solution of morphine and ferric chloride in acetic acid. The Salt
dissolves in water with a blue color and slight decomposition. The
well known color reaction of morphine with ferric chloride is there-
fore due to the formation of this double salt. Caffeine, pyridine and
quinoline also form double salts with ferric chloride. As these alka-
loidal double salts are difficultly soluble in hydrochloric acid they
can be used for determining the équivalents of alkaloids.
The compounds with ferrie bromide are generally unstable but
the following salts could be prepared in pure condition. Cinchonidine
hydrobromide ferric bromide, C19H22N2O.H. Br. FeBra.2H2O, caffeine
hydrobromide ferric bromide, Cs H10N4O2. HBr. Febr8.H2O, and quino-
line hydrobromide ferric bromide, CoH7N.H.Br. Fe Bra. They were
made by adding ferric bromide and strong hydrobromic acid to
solutions of the bases in dilute hydrobromic acid.
(J. pr. Chem. [2], 1906, 74, 161.)
* A11agyrine.
G. Goessmann has tried to separate the two alkaloids, anagyrine
and cytisine, which according to Partheil and Spasski (Apoth. Zug.
1895) are present in Anagyris foetida. The alkaloids cannot be
Separated from each other by fractional distillation or by means of
7
mercuric chloride which according to Partheil precipitates only
anagyrine from a solution slightly acidulated with hydrochloric acid.
It was found that in presence of little acid both alkaloids are
precipitated while much acid keeps them both in solution. The
method of Litterscheid (Arch. Pharm., 1900, 184) which consists in
passing a current of hydrochloric acid gas into a solution of the
alkaloids in absolute alcohol was found to be connected with con-
siderable loss of material. An attempt to separate the alkaloids by
means of hydrogen peroxide which according to Freund and Fried-
mann (Ber. 1901, 605) converts cytisine into a difficultly soluble
crystalline oxide also was not successful. Even after several weeks'
standing the solution of the mixture of the alkaloids in hydrogen
peroxide did not deposit any crystals.
The best results were obtained by treating the solution of the
alkaloids in absolute alcohol with phenyl mustard oil which combines
with the secondary cytisine to a crystalline phenylcytisine thiourea
while the tertiary anagyrine is not affected. After filtering off from
the cytisine compound and evaporating the alcohol from the filterate
the residue was warmed with dilute hydrochloric acid which converts
the anagyrine into a soluble hydrochloride while the excess of the
phenyl mustard oil separates out as an oily liquid consisting partly
of unchanged mustard oil and partly of xantogen anilide. The
solution of anagyrine hydrochloride was made alkaline and shaken
out with chloroform. After removing the chloroform in vacuum and
distilling the residue under reduced pressure the anagyrine was ob-
tained in the form of a yellow brittle mass which on exposure to air
soon becomes moist and sticky.
Analysis of the alkaloid gave figures which did not quite corre-
spond to the formula, C15H22N20, given by Partheil. As the a nagyrine
was free from cytisine it must be assumed that it still contained
some other impurities.
From the phenyely tisine thiourea the cytisine can be recovered
by heating the urea compound for five hours to 150° with strong
hydrochloric acid. The reaction seems to go according to two
equations
* NH.C6H5
1. scó + HCl = Co H5ONS + HN=C11H 18 NO.HCl
N=011 H13NO
2. Co FIGCNS + HCl + 2H2O = CO2 + H2S + C6H5NH2.HCl
8
The aniline formed in the reaction was removed by distillation
with steam after making the liquid alkaline and the cytisine was
then obtained by shaking the liquid with chloroform. The purity of
the recovered cytisine was shown by the optical rotation and by
titration using iodoeosin as indicator. (Arch. Pharm., 1906, 20.)
Apomorphine.
According to D. B. Dott apomorphine hydrochloride is soluble
in 49 parts of water at 25° C., not in 39.5 parts as given in the
U. S. P. (Pharm. J., 1906, v. 22, 345.)
R. Pschorr continues his investigations on the constitution of
apomorphine. When apomorphine is methylated by means of
dimethyl sulphate, dinnethyl apomorphinemethine, C14H1(O.CH3)2.-
CH2CH2.N(CH3)2, is formed which in the previously described way
can be decomposed into trimethylamine and dimethoxy vinyl-
phenanthrene, C14H1.(O.CH3)2.CH = CH2. When the latter is oxidized
with potassium permanganate in acetone solution dimethoxyvinyl
phenanthrene carboxylic acid together with the corresponding glycol,
C14H 7 (O.CH3)2.C.H.O.H.CH2.OH, are formed. The glycol was converted
into an acetyl derivative by means of acetic anhydride. Attempts
to reduce demethoxyvinylphenanthrene with sodium amalgam were
not successful. The same negative results were obtained on trying
to reduce the previously described tribromdimethoxyvinylphenan-
threne and the pentabrom dimethoxyvinylphenanthrene. The latter
is formed by further bromination of the tribromderivative in chloro-
formic solution.
When dimethylapomorphinemethine is distilled with zinc dust
two isomeric ethylphenanthrenes are obtained. They were named
4- and 6 ethylphenanthrene. The separation of these two hydro-
carbons was accomplished by fractional distillation with steam.
Among the other products of the distillation with zinc dust were
Obtained hydrocyanic acid, trimethylamine and anmonia. As the
two ethylphenanthrenes, C16H14, obtained from the “methine” base,
neither of them were identical with the 9-ethylphenanthrene obtained
from phenanthryl-9-methyl carbinol, C14H1.C.H.OH.CHs, the ethyl
groups in the former cannot be in the positions 9 or 10.
The constitutions of apomorphine, dimethylapomorphinemethine
and dimethoxyvinylphenanthrene are supposed to be as follows:


º /N
no.º. CH3.O/ N
|
4,
HO /N. CH3.ON /N
Nº. Y N
ºn 9 /
º/ You. Y
* , ; & | /*
7
N
NZ `oh. H. `oh-oh,
Apomorphine. Dimethoxy vinylphenanthrene.

N
|
/º/ N(CH3)2
J.
|
CH2. CH2
Dimethylapomorphinemethine.
(Ber., 1906, 3124.)
Bebeerine.
In an investigation upon the alkaloids of Radix Pareirae bravae
M. Scholtz shows that the root contains d, l, and racemic bebeerine.
From the acidulated aqueous extract of the root the alkaloids are
precipitated in amorphous condition upon addition of sodium car-
bonate. The amorphous precipitate can be partly converted into
crystalline d and l bebeerine by extracting the precipitate with ether,
evaporating the ether to dryness and recrystallizing the residue from
methyl, alcohol. When recrystallized from most other solvents the
crystalline bebeerine again becomes amorphous. The part insoluble
in ether contains the racemic modification of bebeerine which can be
extracted by pyridine and reprecipitated by methyl alcohol. The
10
racemic modification is almost completely insoluble in acetone,
chloroform or ether. Both the d and the l modifications of crystalline
bebeerine melt at 21.4° while the racemic form whether isolated from
the root or prepared by mixing equal amounts of the d and l varieties
melts at about 300°.
Bebeerine contains a phenolic OH group, one CH3O and one
N.CH3 group. It is soluble in alkalies and is reprecipitated from the
alkaline solution by ammonium chloride. A benzyl iodide was pre-
pared by digesting the chloroformic solution of the alkaloid with
benzyl iodide and recrystallizing the compound from methyl alcohol.
The benzyl iodide melts at 225° and is insoluble in ether. The optical
rotation of bebeerine is [a]n 25 = + 297°. The amorphous variety
of the optically active bebeerines melts at about 180°.
As has been frequently observed with other alkaloids the am-
monium base of bebeerine, unlike bebeerine itself, has no physiological
activity. The crystalline d modification is considerably more active
than the l variety. The amorphous bebeerine is much more active
physiologically than the crystalline modifications. As the amorphous
variety is prepared from the crystalline variety, the lesser activity of
the crystalline alkaloid must be due to its more difficult resorption.
(Arch. Pharm., 1906, 555.)
Brucine.
According to W. Marckwald and R. Meth the salt obtained when
One molecule of brucine is brought together with one molecule of
synthetic cinnamic acid is identical (not only isomeric) with the salt
obtained from brucine and natural cinnamic acid under the same
conditions. It is shown that the supposed isomeric salt obtained by
Erlenmeyer jun. was an acid salt containing two molecules of
cinnamic acid to One molecule of brucine. The neutral salt obtained
from either the natural or the synthetic acid has an optical rotation
of -19.5° while the acid salt is almost inactive, its rotation being
Only −4.2° giving for a one per cent. solution in a two decim. tube
a rotation of –5'. The acid salt is in reality not an acid salt in
the ordinary sense, it is to be regarded as a neutral salt containing
One molecule of cinnamic acid of crystallization. This is shown by
the fact that when recrystallized from benzene the neutral salt con-
taining one molecule of benzene of crystallization crystallizes out
while One molecule of cinnamic acid remains in solution.
(Ber. 1906, 2598.)
11
Caffeine.
Brissemoret has prepared definite compounds of caffeine with
salicylic, gallic and protocatechuic acids by mixing the hot solutions
of the components and setting them aside to cool.
While the commercial caffeine salicylate is only a mixture of
caffeine and salicylic acid prepared by rubbing together the com-
ponents in dry condition the substances prepared by the author are
definite chemical compounds. This is shown by the fact that these
compounds always crystallize out in molecular proportions even
when the hot solutions contain an excess of one or the other of the
components.
Compounds similar to those of caffeine were also obtained from
other xanthine derivatives. (Bull. soc. chim. 1906, 316.)
Columbanime.
E. Günzel acting on the suggestion of J. Gadamer has made an
investigation of the alkaloids of columbo root. The statement of
Gordin (Arch. d. Pharm. 240, 146) supported by that of Gadamer
(ib. 240, 450) about the absence of berberine from this root is
corroborated. The root seems to contain several alkaloids nearly
related to but not identical with berberine. Like berberine the
columbo root alkaloids are quaternary bases. The preparation of
the alkaloids was as follows. The ground drug was extracted with
alcohol, the alcoholic extract, after addition of some water, mixed
with ether which precipitated some sticky dextrin-like substance, and
the clear liquid concentrated to small bulk. The extract was now
diluted with water, shaken out with ether, and the alkaloids precipi-
tated from the aqueous solution by means of potassium iodide. The
precipitate consisting of a mixture of different alkaloids was treated
with boiling alcohol and in this way two iodides were obtained.
The alkaloid underlying one of the iodides was called columbamine
and that underlying the other alkaloid was called alkaloid B. An
attempt to precipitate the alkaloids with strong hydrochloric acid
after dissolving the extract in hot lime water and filtering the
solution (Bödeker's method) gave negative results.
The analysis of columbamine iodide would seem to indicate that
the formula of this compound is C21H22NO5I and that the alkaloid
contained 4 methoxyl groups. No methylimide group could be found.
As silver nitrate did not precipitate the iodide quantitatively the
12
estimation of iodine was made by Carius' method. The base under-
lying the iodide sems to have the formula C21H22NO5.OH or
!C21H 21NO5.H2O.
On digesting the columbamine iodide with silver chloride it was
converted into columbamine chloride which crystallizes in two forms
one containing 2% molecules of water of crystallization the other
containing 4 molecules. A chloraurate, a chloroplatinate and a
nitrate of columbamine were prepared but not analyzed. An acid
sulphate of columbamine, C21H22NO5. HSO4, was prepared by digest-
ing columbamine iodide with silver sulphate, filtering off the silver
iodide and removing the excess of silver by means of hydrogen sul-
phide. The sulphuric acid in the compound could not be precipitated
by barium chloride. The sulphur was therefore estimated by Carius’
method.
On dissolving columbamine iodide in ammonia water and digest-
ing the solution with an excess of yellow ammonium sulphide a penta-
sulphide (C21H22NO5)2S5 crystallizes out in greenish-black crystals
melting at 139°. They could not be recrystallized from alcohol with-
out decomposition.
Tetrahydrocolumbamine is formed when columbamine iodide is
reduced with zinc and sulphuric acid, the liquid saturated with am-
monia and shaken out with ether. In the reduction a molecule of
hydriodic acid is split off.
('21 H22 HO5I-H 4H = C21 [I2O NOs + HI
Columbamine iodide. Tetrahydrocolumbamine.
Tetrahydrocolumbamine forms a hydrochloride which is almost
completely insoluble in cold water. The reduced base seems to con-
tain a phenolic hydroxyl group as it is soluble in an excess of sodium
hydroxide and ether does not extract the base in presence of sodium
hydroxide unless an excess of ammonium chloride is added to the
alkaline solution A gold and a platinum salt of tetrahydrocolum-
bannine were obtained by the usual methods.
On reducing columba mine sulphate electrolytically a crystalline
substance was obtained melting at 228°. The formula of the new
compound was not éstablished. (Arch. d. Pharm. 1906, 257.)
Cinchona Alkaloids.
After a detailed review of the chemistry of the cinchona bases
W. Koenigs reports some new experiments on meroguinene.
13
That the four principal cinchona alkaloids, cinchonine, cinchoni-
dine, quinine and quinidine are derivatives of quinoline was established
by the formation of either quinoline itself or of para-methoxyquino-
line when the alkaloids are melted with potassium hydroxide.


ſº chº
| | i | |
Ny/ Nº \/ N Y
Quinoline. Para-Methoxyquinoline.
(I) - (II)
Upon oxidation these alkaloids give among other products either
cinchoninic or quininic acid
gon CO2H
º ` chºNºN
| |
NNy/ NY * ~/ º
cinehonine acid. Quininic acid.
(III) (IV)


Hence the formulas of the alkaloids were decomposed into two
halves linked together by the Y-atom of the quinoline or p-methoxy-
quinoline molecule º
CoPIGN Co H5 (O.CH3) N
|
C10H16NO C10H16NO
Cinchonine and cinch Onidine. Quinine and quinidine.
Of these halves the quinoline part is generally called the first
half, the other part the second half of the molecule.
On treating cinchonine with ethyl iodide one molecule of the
latter is taken up with the formation of a colorless monoiodoethylate,
but when a molecule of cinchonine is first treated with a molecule of
hydriodic acid and the resulting monohydriodide then treated with
ethyl iodide a hydriodide of another iodoethylate is formed. When
set free by ammonia from the hydriodide this iodoethylate was found
14
to have a yellow color and to resemble quinoline iodoethylate in
behavior. Hence the colored iodoethylate contains the C2H5I group
linked to the nitrogen atom of the quinoline half of the molecule.
This was still further shown by the conversion of the yellow iodo-
ethylate by means of silver nitrate into the corresponding ethyl
nitrate and the oxidation of the latter to the ethyl nitrate of cin-
choninic acid.
ºn
/N /N
ſº Y N
| |
N /N /

NZ N/ C2H5
N&
N
NO3
Ethyl nitrate of cinchoninic acid.
It follows from this that the two iodoethylates of cinchonine
have the following formulas:
Co H 6N Co H6.N. (2 H5I
| |
C10H16NO.C2H5I C10H16NO
Colorless. Yellow.
The fact that when cinchonine is treated either with one molecule
of ethyl iodide or with one molecule of hydriodic acid the alkyl
iodide or the acid go to the nitrogen atom of the second half shows
that this nitrogen atom is more basic than that of the quinoline
part of the molecule. e
As all the four cinchona bases give monoacetyl derivatives when
treated with acetic anhydride and as they are all tertiary bases they
must contain an OH group. When cinchonine or cinchonidine are
heated with hydrochloric acid they undergo an internal rearrange-
ment and are converted into isomeric compounds, apocinchonine and
apocinchonidine. Under the same conditions quinine and quinidine
also undergo an internal rearrangement, but in this case methyl
chloride is also eliminated so that the formula of apoquinine is
CoH5(OH) N
|
C10H15 (OH) N
Apoquinine is isomeric with cupreine and can be obtained from
the latter by heating it with hydrochloric acid. Quinine would,
15
therefore, seem to be the methyl ether of cupreine. When cupreine
is methylated by means of methyi iodide in presence of alkali it is
converted into quinine. If instead of the methyl group, other
groups, like the ethyl, propyl or amyl groups are introduced com-
pounds are formed which are known as quinethyline, quin propyline
or quinamyline.
The four cinchona bases contain a C=C group and are, there-
fore, easily attacked by potassium permanganate in acid solution
and are capable of taking up one molecule of bromine forming
dibromides. When these dibromides are treated with potassium
hydroxide in alcoholic solution either one or two molecules of hydro-
bromic acid are eliminated giving monobrom derivatives in the first
case, in the second case dehydrobases containing two atoms of
hydrogen less than the corresponding bases.
Upon oxidation with cold potassium permanganate the four
cinchona bases yield formic acid and the so called “tenines”: cincho-
tenine, cinchotenidine, quinotenine and quinotenidine. Unlike the
cinchona bases these “tenines” are saturated bases containing a
CH2 group less and two atoms oxygen more than the corresponding
bases. For these reasons the cinchona bases are supposed to con-
tain a vinyl group which, being converted into a carboxyl group in
the formation of the “tenines”, gives the formic acid
R.CH=CH2+o, - R.Co., H+H.CO2H
As the “tenines” are tertiary bases and form acyl derivatives
they must still contain the OH group of the corresponding bases.
That this is so is shown by the formation of one and the same
benzoyl cinchotenine whether benzoyl cinchonine is oxidized or cincho-
tenine is benzoylated.
Among the products of oxidation of the cinchona bases are
found saturated bases containing two atoms of hydrogen more than
the cinchona bases. They were called hydrocinchonine, hydrocin-
chonidine, hydroquinine and hydroquinidine. They are supposed to
accompany the cinchona bases in the bark and can only be difficultly
separated from the latter.
When the cinchona bases are warmed with phosphorus penta-
chloride they are converted into chlorine derivatives in which Cl has
replaced an OH group. Reduction with iron and acetic acid replaces
the Cl by H and converts them into desoxy bases (desoxycinchonine,
16
desoxycinchonidine, etc.). If the chlorine derivatives are boiled with
potassium hydroxide in alcoholic solution they lose hydrochloric
acid and compounds are formed whose formulas differ by the elements
of H2O from the formulas of the corresponding cinchona bases. Cin-
chonine and cinchonidine give under these conditions cinchene,
C19H2ON2, while quinine and quinidine give quinene, C20H22N2O. On
boiling cinchene or quinene with hydrobromic acid the former is
converted into apocinchene and the latter into apoquinene
C19H2ON2 + H2O = C19H19NO + NFI 3
Cinchene. ApOcinchenne.
C19H10(O.CH3)N2 + H2O + HBr – C10H18(OH) NO +NH3+ CH3Br.
Quinene. Apoguinene.
The constitution of these two compounds was found as to be as
follows:
ºil. ºn.
/N /N
ſ Y-C2H, ſ Y-C, H 5
–OH | –OH
N / N
Y sº
|
/N /N /N /N
ſº Y \ Ho—ſ Y \
A | 9 /
sº Nº * NZ NZ
N * N
Apocinchene. \ ApOquinene.
(V) (VI)


On heating apoquinene with amonia-zinc chloride, diazotizing the
resulting amido compound and then eliminating the diazo group by
means of boiling alcohol and powdered copper the apoquinene was
converted into apocinchene. As cinchene and quinene behave very
much alike they are most probably related to each other in the same
way as apocinchene and apoquinene i. e. apoquinene is p-oxyapo-
cinchene and quinene is p-methoxycinchene.
Both cinchene and quinene are easily hydrolyzed by dilute phos-
phoric acid, cinchene yielding meroquinene and lepidine (7-methyl-
quinoline) and quinene yielding meroquinene and para-methoxy-
lepidine)
17
C19H2ON2 + 2 H2O = Co H15NO2 + C10H9N
Cinchene. Meroguinene. Lepidine.
C19H19 (CH3O) N2 + 2 H2O — C9H15NO2 + C10H8N(CH3O)
Another oxidation product of ordinary cinchonine is cincholoi-
pone, Colºſ. 7NO2, whose formation must be ascribed to the dihydro-
cinchonine (cinchotine) which usually contaminates cinchonine, be-
cause pure cinchonine does not give upon oxidation cincholoipone.
On the other hand when dihydrocinchonine (cinchotine) is passed
through the reactions by which meroguinene is formed from cincho-
nine the dihydrocinchonine is first converted into dihydrocinchene
which is then further hydrolyzed to cincholoipone
C19H22N2 + 2 H2O = Co H17NO2 + C10H 9N
Dihydrocinchene. Cincholoipone. I.epidine.
The four cinchona bases as well as their corresponding “tenines”
and “toxines” yield upon oxidation cincholoiponic acid, CsPI18NO4.
As the acid forms a nitrosamine and an acetyl derivative it must
contain an NH group. But while the acid itself is monobasic as
shown by titration and analysis of its lead salt the nitrosamine and
the acetyl derivative are dibasic acids. This can be explained by
assuming that while there are two carboxyl groups in cincholoiponic
acid the basic NH group weakens the acid properties of the com-
pound to such an extent that it behaves like a monobasic acid. Bmt
when the basic properties of the NEH group are destroyed by replacing
the hydrogen by an acetyl or a nitroso group the functions of the
two carboxyl groups are restored to their full strength.
Upon distillation with zinc dust cincholoiponic acid yields pyridine
while cincholoipone under these conditions yields 3-ethylpyridine. As
cincholoipone is oxidizable to cincholoiponic acid Skraup ascribed
following formulas to cincholoipone and cincholoiponic acid
CH2 CH2
/N - N
H2C/ NCH-C2H5 H2C / NCH-CO2H
CH3 ſ | CH3
C& | C&
H2CN /*\ H2CN /*N
NZ CO2H NZ CO2H
NH NH
Cincholoipone. Cincholoiponic acid.
(Skraup.) (Skraup.)
But later investigations showed that the constitution of these
two compound must be similar to that of meroguinene which occupies
18
an intermediate position between them being reducible to cincholoi-
pone and oxidizable to cincholoiponic acid. As the behavior of mero-
quinene towards bromine and potassium permanganate is like the be-
havior of the cinchona bases towards these reagents the vinyl group
must be present in meroguinene. Meroquinene also contains an NH.
and one carboxyl group but the acid function of the latter appears
only when the H of the NH group is replaced by an NO or acetyl
group. Upon distillation meroguinene gives 3-ethyl-rmethylpyridine.
All these considerations would seem to indicate that the formulas of
cincholoipone, meroguinene and cincholoiponic acid are as follows:
CH-CH2—CO2H CH-CH2—CO2H
/N / N
hº NCH-CH2.0Hs hº NCH-CH=(XH2
| |
| | |
Hºch, Hºch.
*. NH NH
Cincholoipone. Mero quinene.
(VII) e (VIII)

ºn-on
H2C/ \ch-coln
|

|
H20 N /CH2
NH
Cinch Oloiponic acid.
(IX)
To these formulas v. Miller and Rohde raise the objection that
as cincholoiponic acid gives the phthalein reaction the two carboxyl
groups Ought to be in Orthoposition to each other, but as hexa-
hydroisophthallic acid also gives the phthalein reaction the above
objection is not valid.
That cincholoipone contains a CH2.002H group in the y-position
of the piperidine ring is shown as follows: When 3-ethyl-7-methyl-
pyridine (8-collidine) is condensed with formic aldehyde, monomethyl-
B-collidine, C2H5.C6H3N.CH 2.0H2.OH, is formed which is reducible to
the corresponding piperidine derivative, C2H5.06 HoN.CH2. CH2.OH.
When by means of hydriodic acid and amorphous phosphorus the
OH group in this alkine is replaced by an I-atom the resulting com-
pound easily loses hydriodic acid and is converted through “inner
alkylization” into a compound of the formula, C10H17N, which was
19
named 3-ethylquinuclidine. As the alkine itself is a saturated
secondary base while the 8-ethylquinuclidine is a saturated tertiary
base the successive steps in the transformation must be as follows:
CH.CH2.0H2OH yach.cº.
/N N
H2C NCH.C2.H5 hº NCH.C2H5
——). | ——).
| |
H2CN /CH2 H2CN CH2
\4
NH NH
Monomethyl-3-collidine.
g-Ethylquinuclidine.
Now if the ester of cincholoipone is reduced by means of sodium
in alcoholic solution and the resulting alkine treated in the same
way as the above monomethylol (3-collidine the resulting compound
is identical with 8-ethylquinuclidine. Hence the CH2.002 H in cincho-
loipone must be in the r-position and the reaction must be as
follows:
CH.CH2.UO2.02 H 5 * CH.CH2.0H2.OH
/N ^
H2C/ Sºhº Hacº NCH.C.H.
| | – || || –
H2CN / CH2 H2CN / CH2
NZ NZ
Ethylester of cincholoipone. Monomethylol 3-collidine
}H
N
H.0/ NCH.C2H5
CH2
|
CH2
Hºyon 2 &
N
g-Ethylquinuclidine.
From the constitutional formulas of meroguinene and cincho-
loiponic acid (XIII) and (IX) it is easy to deduce the formula of

20
cinchene and from this the formulas of the cinchona bases themselves.
As the cinchona bases containing one double binding are not hydro-
lyzable whilecinchene with two double bindings is hydrolyzable to mero-
quinene and lepidine it must be assumed that the splitting up of
cinchene into meroguinene and lepidine takes place at the new double
binding which in the conversion of cinchonine into cinchene is formed
by replacement of OH by Cl and subsequent removal of HCl. In an
exactly similar way benzylidene lepidine, NC90H =CH.C6H5, when
heated with dilute acetic acid is easily hydrolyzed to benzoic alde-
hyde and lepidine.
NCOH 60H : CH.C6H5 + H2O = C6H5OHO + NCpTI6
Hence in cinchene the lepidine rest must be linked to the
meroguinene rest by means of a double binding between the carbon
atom which in cinchonine contains the CH group. The formula of
cinchene is then
(H
/N
H2C/ | NCH.CH=CH2
CH2
|
CH2
CN | ZCH2
|
| N
CH
|
C9H 6N
Cinchene.
(XI)

In the hydrolysis of cinchene we ought to get through the
addition of One molecule of water lepidine and a tertiary base con-
taining an aldehyde group in place of the C atom which in cinchene
is doubly linked to the lepidine rest. But as meroguinene contains
a carboxyl instead of an aldehyde group and is a secondary base
we must assume that in the hydrolysis of cinchene two molecules of
water are taken up and that as the linking between the meroquinene
rest and the lepidine rest is destroyed at the same time the linking
between the N atom and the C atom linked to the lepidine rest is
also destroyed. The tertiary N becomes a secondary NH group by
taking up one H atom while the C atom linked to the lepidine rest
becomes a carboxyl group linked to a CH2 group which is situated
in the r-position of the piperidine nucleus of meroguinene.
21
(H (H.CH2.0O2H
/N N
H2O h CH.CH = CH2 H2C NCH.CH = CH2
CH2
| + 2 HO = + Co.He(CH3) N
CH2 |
CN /en. H2CN /CH2 Lepidine.
| N
| N NH
}H
Meroquinene.
C9HeN
Cinchene.

From the nature of the conversion of the cinchona, bases into
cinchene or quinene it is easy to see that the formulas of these bases
are as follows:
9t 9t.
N N
H2O/ | NCH.CH=CH2 H2O/ | NCH.CH=CH2
CH2 CH2
| |
Hoc's "ch hoc "ºoh
• * /CH2 HO.C XH2
| N/ N/
N N
gº. CH2
CH C CH


Ho/Nº/\ch chocº N NCH
| | | | *
"Nº." nº/ /ch
CH N
Cinchonine and Cinchonidine. Quinine and Quioidine.
(XII) (XIII)
The conversion of the bitertiary cinchona bases into the so-called
“toxines” which contain one tertiary and one secondary nitrogen
atom can be explained by assuming that at first a molecule of H2O
adds itself to the molecule of the base but is then split off again
in a different way according to the following scheme:
C C C
N /N /N
c/! NC C/ ! NC C/ & NC
t + H2() == = t + H2O
J |
HO.CN | ZU (HO)2C | Z'C OC ZC
N/ & /
N N H NH
H2 CH2 º


22
The formulas of cinchotoxine and quinotoxine are therefore as
follows:
CII º
/N N
CH2/ | NCH.CH=CH2 CH2/ | NCII.CH = CH2
CH2 CH2
| - |
CH2 (H2
OC /CH2 OC
N II | NH
CH2 CH2
|
C9H8N CoPIs (O.CH3) N
Cinchotoxine (Cinchoincine). Quinotoxine.

The isomerism of cinchonine with cinchonidine and of quinine
with quinidine is supposed to be due to the asymmetry of the
carbon atom to which is linked the OH group. That this carbon
atom is not linked to hydrogen is shown by the fact that when the
OH group is replaced by H two isomeric but not identical desoxy
bases are obtained from each pair of the cinchona bases while the
toxine obtained from cinchonine is identical with the toxine obtained
from cinchonidine and the same is true of the toxine obtained from
quinine and quinidine. The reason of the identity of these toxines
must be the disappearance of asymmetry from the carbon atom
linked to the OH group by conversion of this group into a CO
group. Hence if the OH group were linked to a carbon atom linked
to H the formation of the desoxy bases would involve a change of
a ("H.OH into a CH2 group. As such a change would also destroy
asymmetry of the C atom there would result identical not only
isomeric desoxy bases from each pair of the cinchona, bases.
The isomerism of a- and S-i-cinchonine which are formed from the
latter by heating it with halogen acids is according to Skraup of
stereo chemical nature and the impossibility of detecting an OH
group or a double binding in the a- and 8-bases is supposed by him
to be due to steric interferences of the groups with the reactions of
each other. According to the author the difference between the a-
and 8-base is really of a stereo-chemical nature but both of them
differ in structure from cinchonine. Their formula is as follows:
23
CH
H2C ().H2 / CH2
C.O.CH
|
CH3|CH2
N
(H2——C9HGN
O-àn d–3—i-cinch Onine.
The formation of two stereoisomeric bases from cinchonine is
therefore due to the fact that in this reaction another carbon atom
becomes asymmetric. When either a- or 8-cinchonine is heated with
hydriodic acid the linking between the oxygen atom and the carbon
atom belonging to the vinyl group of cinchonine is destroyed and a
compound is formed which is identical with hydriodo cinchonine ob-
tainable directly from cinchonine through the addition to it of one
molecule of hydriodic acid
CH
/N
H2C/ | NCH.C.H.I.CH3
CII 2
sº
CH2
HO.CN | "CH2
/ /
/ N
C9H6N
/
&#.
Hydriodocinchonine.
Owing to the presence of three asymmetric carbon atoms in the
molecule of the cinchona bases there ought to be eight optically
active and four racemic isomerides of cinchonine or quinine. For
this reason the author doubts the possibility of ever making quinine
synthetically.
The meroguinene (VIII) was prepared either by hydrolysis of
quinene or cinchene, or by oxydation of cinchonine. For the hydro-
lysis of quinene or cinchene they are heated for ten hours under
pressure to 170–180° with dilute phosphoric acid (1 in 5), the
excess of acid removed by means of barium hydroxide and after

24
removal of excess of the latter by a current of carbon dioxide the
lepidine formed in case cinchene is used or the p-methoxylepidine
formed in case quinine is used are removed by distillation with
steam. From the resinous impurities the meroguinene is separated
by means of alcohol in which it is very little soluble. That the
meroguinene from cinchene is identical with the meroguinene obtained
from quinene was shown by the identity of the melting point and
optical rotation and by the identity of the melting point of the
hydrochloride of the ester obtained by treating the meroguinene
with alcoholic hydrochloric acid.
The lepidine and the para-methoxylepidine were identified by the
boiling point, by the melting points of their acid sulphates and the
analysis of their chloroplatinates.
Cinchene can also be hydrolyzed to meroguinene by heating its
acid tartrate either with water under pressure to 170–180° or with
glycerin containing a little water to the same temperature in an
open vessel. But the hydrolysis under these conditions is very in-
complete.
The solution of p methoxylepidine in very dilute sulphuric acid
has an intensely blue fluorescence and assumes a green color upon
the successive addition of chlorine water and ammonia.
The preparation of meroguinene by oxidation of cinchonine was
carried out according to the method of the author (Ber. 97, 1879)
or Skraup (Ann. 201, 291).
Another method by which meroguinene can be obtained is by
oxidation of cinchotoxine (Skraup, Monatsh. 1903, 298.)
Meroquinene is easily soluble in water, very difficultly soluble in
cold alcohol and almost insoluble in ether or chloroform. It is
neutral toward litmus and melts at 223–224°. It sublimes to some
extent in vacuum at about 210–230° but cannot be purified by
distillation in vacuum in a current of hydrogen. It has an optical
rotation of [a] = +27.58 and is precipitated by most alkaloidal
reagents. It was converted into a hydrochloride by evaporating to
dryness its solution in dilute hydrochloric acid. It also forms a
chloraurate and a chloroplatinate. It does not form salts with
metallic oxides but is easily esterifiable. The esters of meroguinene
can be made either by passing hydrochloric acid gas into its alcoholic
solution or by Warming it with alcohols and sulphuric acid. The
ethyl ester of meroguinene forms a hydrochloride which being
2.5
soluble in chloroform can be easily separated from meroguinene
hydrochloride which is insoluble in this solvent.
The presence of an NH group in meroguinene was shown by
converting it into an acetyl and a nitroso derivative. The acetyl
derivative was obtained by boiling meroguinene with acetic
anhydride, removing excess of anhydride first by evaporation
and then by means of alcohol and recrystallizing the compound
from ether-alcohol. The acetyl compound still has slightly basic
properties its solution in dilute sulphuric acid being precipitated
by phosphotungstic acid. It also has acid properties and can be
removed from etherial solution by shaking with dilute sodium car-
bonate solution. The acetyl meroguinene prepared by above method
is generally accompanied by a small amount of the acetyl compound
of the meroguinene ethyl ester which remains in the ethereal solution
when the latter is shaken with alkaline carbonate.
The nitrosamine of meroguinene was obtained in the form of a
calcium salt by adding sodium nitrite and dilute sulphuric acid to
an aqueous solution of meroguinene, then shaking out the liquid with
ether and, after removal of the ether by evaporation, taking up
the residue with calcium carbonate in presence of water. Neither the
nitrosamine of meroguinene itself nor the nitrosamine of meroduinene
ethyl ester give Liebermann’s nitroso reaction. The NO group in
these compounds seems to be more firmly attached than in ordinary
nitrosamines.
The presence of an NH group in meroguinene was also shown by
its combining with a-naphtylisocyanate to a derivative of a-naphtyl
urea which separates out upon addition of acid. As the naphtyl
compound still contains the CO2H group of meroguinene it is soluble
in ammonia.
The oxidation of meroguinene to cincholoiponic acid (IX) was
accomplished by boiling meroguinene with chromic acid mixture and
converting the product into the hydrochloride of cincholoiponic acid.
The free acid was obtained by treating the hydrochloride successively
with silver carbonate and H2S. A better yield of the acid can be
obtained by using potassium permanganate instead of chromic acid.
The reaction is as follows:
Cobi 15NO2 + O.4 = ('s H13 NO.4 + H.CO2H
Meroquinene. ('incholoiponic acid.
26
The formation of formic acid indicates the presence of a vinyl
group in meroguinene. The formic acid was separated from the
cincholoiponic acid by distillation and identified as a barium salt.
The cincholoiponic acid was also converted into a barium salt and
the latter transformed into the ethyl ester of cincholoiponic acid by
the usual method. The ester was saponified by repeated evaporation
with hydrochloric acid and the resulting hydrochloride of the free
base then identified by the melting point.
The reduction of meroguinene to cincholoipone (VII) could not
be accomplished either by means of sodium in presence of alcohols
or by heating the meroguinene with hydriodic acid and phosphorus
but was carried out by Willstätter's method (Ber. 1900, 368) in the
following way: The meroguinene was digested for 8–14 days with
hydriodic acid and then treated with zinc dust. After removal of
most of the hydriodic acid by evaporation and subsequent precipi.
tation with lead acetate, the zinc and lead were removed by means
of sodium carbonate and the liquid then shaken with silver chloride
and some hydrochloric acid, This converts the cincholoipone into
its hydrochloride from which it was set free by shaking the salt with
silver carbonate and subsequent removal of the last trace of silver by
means of sulphuretted hydrogen. The cincholoipone is not easily
affected by potassium permanganate in presence of sulphuric acid
showing the absence of double bindings. It was identified as a
hydrochloride, chloraurate and an acetyl derivative. The latter was
prepared by warming the cincholoipone hydrochloride with silver
acetate and, after removal of the silver chloride, heating the filtrate
with acetic anhydride. The cincholoipone was also converted into
the hydrochloride of its ethyl ester.
The meroouinene used for the preparation of cincholoipone was
prepared by Oxidation of cinchonine and was therefore liable to be
contaminated with other substances formed in this oxidation. In
Order to show that cincholoipone is really a reduction product of
meroguinene perfectly pure meroguinene was prepared from brom-
meroguinene and then reduced by the same method as was used for
the meroquinene from cinchonine. The resulting cincholoipone was
found to be identical in both cases. Attempts to reduce brommero-
quinene directly to cincholoipone without first reducing it to mero-
Quinene were not successful.
The conversion of meroguinene into 3-ethyl-r-methyl pyridine
27
(3-collidine) was carried out by heating meroguinene to 240° with
hydrochloric acid and mercuric chloride and, after adding barium
hydroxide, distilling the product with steam. The constitution of
the base was shown by the fact that upon oxidation the base yielded
two acids: Cinchomeronic (8–r-pyridine dicarboxylic) and homoni-
cotinic (r—methyl-3-carboxylic) acids. The two acids were separated
from each other by means of their lead salts, the lead salt of cin-
chomeronic acid being insoluble while that of homonicotinic acid is
soluble.
On distilling cincholoipone with zinc and calcium oxide a very
small amount of 3-ethyl pyridine was obtained. It was identified as
a chloraurate.
Brommeroguinene was prepared in the form of a hydrobromide
by adding bromine water to an aqueous solution of meroguinene
and concentrating the liquid to a small bulk. The salt has the
formula, Cohl 4 BrNO2.HBr, and gives off the HBr when treated with
cold silver nitrate while the other bromine atom is removed only by
prolonged boiling with this reagent. The brommeroguinene gives a
NO derivative which does not give Liebermann’s reaction unless heat
is applied. It also gives an acetyl derivative.
Boiling water eliminates bromine from brommeroguinene con-
verting it into oxymeroquinene, CoH14(OH)NO2, while alkalies con-
vert brommeroguinene into meroguinene. As brommeroduinene is
stable towards potassium permanganate it cannot contain a double
binding. Hence in the action of bromine water upon meroguinene
two atoms of bromine attach themselves at first to the double
binding of the vinyl group and then one atom of bromine is split
off together with the hydrogen atom of the carboxylic acid as
hydrobromic acid. The resulting brommeroquinene has therefore the
constitution of a lactone
CH--O
/N | .
H2C/ NCH--CH.CH2. Br

NH
f Brommeroguinene.
Oxymeroguinene, CoEI 14(OH)NO2, was obtained by boiling bron-
meroguinene with water for 24 hours, shaking the liquid with silver
28
chloride and, after removing the silver bromide, evaporating the
filtrate to dryness. From the oxymeroguinene hydrochloride thus
obtained the free oxymeroguinene was obtained by means of silver
carbonate. The oxymeroguinene was converted into a chloroplatin-
ate, a chloraurate and a chloraurate of acetyl oxymeroguinene. The
acetyl compound could not be obtained in the free condition nor
was it possible to esterify oxymeroguinene. Oxymeroduinene is very
stable towards potassium permanganate.
On treating meroguinene éthyl ester with ethyl iodide it is con-
verted into the hydriodide of N-ethyl meroquinene ethyl ester,
CoH18N(C2H5)02.C2H5.HI. The hydriodide was converted into the
corresponding hydrochloride by means of silver chloride and into
the hydrobromide by means of silver bromide. The hydrochloride is
saponified when boiled with dilute hydrochloric acid yielding the
hydrochloride of N-ethyl meroguinene. The free N-ethyl meroguinene
could not be obtained in crystalline form.
When the hydrobromide of N-ethyl meroguinene ethyl ester is
treated with bromine in chloroformic solution it is converted into a
hydrobromide of the dibromide of N-ethyl meroguinene ethyl ester.
When this is boiled, with dilute hydrobromic acid the compound is
saponified and converted into the hydrobromide of N-ethyl brom-
meroguinene. The constitution of these hydrobromides seems to be
as follows:
CH-CH2. OO.O.C2H5 CH-CH2—CO.O
... /N /N |
H2C/ Schoºl. hº NCH-—CH.CH2 Br
| | :
H2CN /CH2 H2C /CH2
Ny/ Ny
N.C2H5 N.('o II;
/N /N
H IBT II Bl'
Hydrobromiſle of the dibromide of Hydrobromide of N-ethyl brom-
N-ethyl mero(Juinene ethyl ester. Imero(linene.
On heating meroguinene in aqueous solution with arsenic acid
one molecule of H2O is taken up with the formation of oxydihydro
meroquinene, CoH17NO3. As shown by the stability of the dihydro-
compound towards potassium permanganate in acid solution it does
not contain the double binding present in meroguinene. When
warmed with iodine in alkaline solution oxydihydromeroguinene
yields iodoform. It combines with hydrochloric acid to form a
29
hydrochloride with elimination of water, hence the hydrochloride of
oxydihydro meroquinene is isomeric with meroguinene hydrochloride.
This elimination of water in the formation of the hydrochloride
shows that oxydihydro meroguinene behaves like an oxyacid which
under the action of strong acid is converted into a lactone. When
warmed with bromine in alkaline solution the hydrochloride of
oxydihydro meroquinene yields carbon tetrabromide. All these facts
would seem to indicate that the compound underlying the hydro-
chloride of oxydihydro meroguinene is a lactone of the following
constitution
CH-CH2—CO.O
H.0/~c | –6– H3
| |
| |
H2(N /CH2
NZ
NH
Meroguinene lactone.
The iodoform and carbon tetrabromide in the above reactions are
formed from the methyl group in the 8-position. (Ann. 1906, 143.)
Cinchonine.
According to Paul Rabe the formula of cinchotoxine proposed
by Koenig (preceeding paragraph) fails to explain why even in
presence of a large excess of amyl mitrite cinchotoxine forms a
monoisonitroso- and not a diisonitroso compound. As by this
formula there is in cinchotoxine the grouping — CH2.0O.CH2 — both
CH2 groups ought to take part in the reaction giving a diisonitroso
compound. gº
Another point that is not well explained by Koenig's formula is
the formation of cinchoninic acid and a nitrile of N-methylmero-
quinene from isonitrosomethylcinchotoxine by Beckmann’s reaction
(Ber. 1905, 2770). When Beckmann's reaction is applied to 4-benzil-
monoxime the latter splits up into benzoie acid and benzonitrile:
cºcoºch. —) Colºſs. CO.OH + C6H5.ON
N.OH
Benzil monoxime.
The isonitrosomethylcinchotoxine forming similar products (an acid
and a nitrile) ought to have a constitution similar to benzilmo-
noxine, i. e. the CO group of the cinchoninic acid must be linked
30
directly to the quinoline nucleus of the isonitrosomethylcinchotoxine
which is not the case if Koenig's formula is adopted:
º CII CH-CH=CH2
|
º CH2
|
ColleN–C º 2
N.OH N. (CII3)—CH2
Isonitrosomethylcinchotoxine.
(By Koenig's formula for cinchotoxine.)
For these reasons the author proposes the following formulas
for cinchotoxine, isonitrosocinchotoxine and cinchonine:
CH2 CH-CH-CH=CH2 CH2——CH-CH-CH=CH2
H. th. {-son th.
C9HoN–-CO th. | Cohe N–CO ºn.
NH–CH2 NH-OH2
Cinch Ot Oxine. ISOnitrosocincho toxine.
CH2— CH-CH-CH=CH2
'H. H.
'H.
|
N UH2
Cinchonine.
C9 IIGN–C(OH)
In this investigation the following compounds were prepared in
collaboration with Karl Ritter.
Cinchonine iodomethylate. This was made by Claus and Müller’s
method, i. e. by boiling cinchonine with methyl iodide in alcoholic
solution.
The conversion of the iodomethylate into methylcinchotoxine is
best carried out in acid solution in presence of sodium acetate (Ber.
1904, 1674; 1880, 2293; 1905, 309; Ann. 1893, 279). The cin-
chonine iodomethylate was boiled for 72 hours with a mixture of
equal parts of glacial acetic acid and sodium hydroxide solution
(1:3) and the cooled liquid, made alkaline with potassium hydroxide,
shaken out with ether. When the ether is distilled off the methyl-
cinchotoxine is left as a crystalline mass.
The conversion of methylcinchotoxine into isonitrosomethyl-
cinchotoxine was carried out by a slight modification of Rhode and
31
Schwab's method (Ber. 1905, 306). The modification consisted in
the following. The alcoholic solution of the sodium salt of the
isonitrosomethylcinchotoxine obtained by that method was mixed
with water and the liquid shaken out with ether to remove the alcohol,
amyl alcohol and amyl nitrite. Atter removing the last trace of
ether from the aqueous liquid by means of a current of air, a current
of carbon dioxide was passed into the liquid till the isonitroso
compound separated out in solid condition.
The splitting up of the isonitrosomethylcinchotoxine into cin-
choninic acid and the nitrile of methylmeroduinene was accomplished
by treating the isonitroso compound with phosphorous pentachloride
in chloroformic solution and distilling the oily liquid which separated
out with steam after adding alkali. From the distillate the nitrile
is extracted by means of ether in presence of solid alkali and purified
by fractional distillation under diminished pressure. The nitrile is a
colorless liquid of a piperidine-ike odor and is soluble in alcohol,
ether and water. It boils at 252—255° under 841 mm. pressure and
at 162° at 49 mm. pressure. It has a specific gravity dº = 0.9505,
an index of refraction N} = 1.4803, a molecular refraction MN, =
49,02 and a specific rotation [a]} = 17.11°. It is a strong base
and forms an iodomethylate, a picrate and a picrolonate. The
formula of the nitrile is
GH-CH=CH-CH=CH.
ČH2
th.
CN Sch-h.
Nitrile of N-methylmeroquinene.
The nitrile, when saponified by boiling for 18 hours with barium
hydroxide, breaks up into ammonia and the barium salt of N-methyl-
meroguinene which separates out as a reddish-yellow viscous liquid.
From the barium salt the free N-methylmeroguinene was obtained
by means of sulphuric acid.
CH2
-CH--—CH-CH=CH2
('H2
CH
CO2H Schº-º.
N-methylmeroquinene.
32
The N-methylmeroguinene is a resinous mass soluble in water,
alcohol and chloroform but insoluble in ether. It has a neutral
reaction and is so easily esterified that when its hydrochloride is
digested with alcohol the hydrochloride of its ethyl ester is obtained.
From the hydrochloride of the ethyl ester the free ethyl ester was
obtained by means of potassium carbonate and ether. The free ester
is a colorless mobile liquid of a strong basic odor and boils at 147°
under 22 mm. pressure. It forms a chloraurate, a picrate and a
picrolonate.
Isonitrosoethylcinchotoxine was prepared from cinchonine iodo-
ethylate by the same method as was used for the preparation of the
isonitrosomethylcinchotoxine from the iodomethylate. The isonitro-
somethylcinchotoxine crystallizes from alcohol in fine needles melting
at 136°, soluble in warm alcohol and chloroform, difficultly soluble
in cold alcohol and benzene but almost insoluble in water or ether.
It was converted into the nitrile of N-ethylmeroguinene by the same
method as was used for the corresponding methyl compound. The
nitrile of N-ethylmeroduinene is a colorless liquid which assumes a
reddish tint on exposure to the air. It has a piperidine-like odor,
is quite soluble in water and is volatile with steam. It boils at 268°
under a pressure of 750 mm. Its iodomethylate melts at 230–233°
with decomposition.
By saponifying the nitrile of N-ethylmeroquinene with strong
sodium hydroxide, acidulating the liquid with hydrochloric acid,
evaporating to dryness and digesting with alcohol the hydrochloride
of the ethyl ester of N-ethylmeroquinene was obtained showing that
the hydrochloride of the N-ethylmeroguinene is very easily esterifiable.
In order to obtain the hydrochloride of the free N-ethylmeroguinene
the hydrochloride of the ethyl ester was saponified by means of
dilute hydrochloric acid.
CH2 CH CH–CH=CH2
(Hg
CO2 H Roº-th.
N-ethylmeroguinene.
The presence of a vinyl group in the N-ethylmeroquinene was
shown by the absorption of bromine in chloroformic solution with
the formation of a dibromide.
33
Isonitrosocinchotoxine was converted into the nitrile of mero-
quinene by the same method as was used for the N-methyl and the
N-ethyl derivatives:
CH2 CH CH–CH2
th.
th.
(N NH bH.
Nitrile of mero(Tuinene.
The nitrile boils at 147—150° under 12 mm. pressure and resembles
in its properties the corresponding N-alkyl derivatives. It was con-
verted into a picrolonate and, after saponification, into the hydro-
chloride of meroguinene ethyl ester.
CH2 CH CH–CH=CH
th.
&H.
CO2. C2H5 sh —CH2
Mero quinene ethyl ester.
(Ann. 1906, 180.)
Cocaine.
On examining an old sample (1891) of cocaine hydrochloride P.
Breteau found it to contain methyl benzoate, benzoic acid and
ecgonine hydrochloride. The formation of these decomposition pro-
ducts of cocaine seems to be due to the presence of moisture in the
salt. Hence the hydrochloride should be particularly protected
against atmospheric moisture. (Bull. soc. chim., 1906, 674.)
By treating cocaine suspended in water with the theoretical
amount of formic acid F. Vigier prepared cocaine formate,
C17H21NO4.0H2O2. The salt crystallizes in white silky needles melt-
ing at 42° and decomposing at a higher temperature. It is soluble
in 41 parts of cold water, the solubility increasing with the elevation
of the temperature up to 80°. At 90° the salt breaks up into
cocaine which separates out in oily drops and formic acid. It is
soluble in about 2% parts of alcohol at 20° but is insoluble in ether,
chloroform, olive oil or vaselin. It has an optical rotation of
–56°40' and gives all the reactions of other cocaine salts.
(J. pharm, chim., 1906, 97.)
34
Conine
It had been supposed by Ladenburg that the reason why natural
d-comine obtained from the plant had a lower rotation than synthetic
d-conine consisted in the natural base always being more or less
contaminated by another base named isoconine while the synthetic
compound was supposed to be true d-conine. Further experiments
have shown that this cannot be so. In the first place no matter
how many times natural d-conine is purified its rotation remains
constant. In the second place all attempts to purify isoconine so
that it would have a constant and lower rotation than natural
d-conine have failed. On the contrary the more the isoconine was
purified the higher became its rotation so that perfectly pure it
must have a higher rotation than natural d-conine. Hence the
author comes to the conclusion that synthetic d-conine is identical
with pure isoconine and has the specific rotation 18.3° while natural
d-conine of the specific rotation 15.6° represents true conine. The
isomerism of natural conine with isoconine the author ascribes to
the asymmetry of the nitrogen atom (Ber. 1901, 2976).
The author has also succeeded in converting the synthetic conine
(isoconine) into the natural base by heating the former to about
300°. Hence the synthesis of natural d-conine is now complete.
The method used by the author in the present work for the
synthesis of conine was the same he had used before except that he
now uses acetic aldehyde at a temperature of 150° instead of paral-
dehyde at 250–260°. (Ber. 1906, 5486.)
Cotarnine.
M. Freund and H. H. Reitz have investigated the behavior of
cotarnine towards Grignard’s solutions. According to previous in-
vestigations (Ber. 1903, 4257) cotarnine, which can be looked upon
as a substituted benzoic aldehyde, behaves like the latter when
treated with an ethereal solution of magnesium and methyl iodide.
At first a secondary alcohol seems to be formed which through the
loss of a molecule of water and closing of the ring is converted into
a-methylhydrocotarnine:
CH3. O CHO CH3.O chººl
o/ N / o/N /
CH2( | → chº | ——).
"N/\ ov/\
CH2.0H2.N.H.CH3 CH2.0H2.N.H.CH3
Cotarmine, (II)
(I)
CH3O each. gº. () gºod.
N N 2.

() / Ny’ OH O y N/ NN.CH3
– chº → chº
ox /N 'ON /\ /CH2
/ N N N/
N CH2.0H2.NH.CH3 / CH2
(III) (IV)
In the present paper various other derivatives of hydrocotarnine
are described which were prepared by means of the organo-metallic
compounds of magnesium. They are mostly crystalline, tertiary
bases, and form crystalline salts with acids. As the carbon atom to
which the new organic radicles are attached is asymmetric the com-
pounds are most probably racemic and it ought to be possible to
decompose them into optical isomerides. They form iodomethylates
with methyl iodide and are converted into aminooxides when treated
with hydrogen peroxide.
ciº CH.R. CH3. O CH.R. O
/N N />
Ny/ NN. (CH3)2.I o/~ `Nº.
| | | ch,< | | | *
O N /N /ch. * O /N /CH2
` Nº.
Iodomethylate of a Rºyarototamine. A mino-oxide of a k-hydrocotormine.
(V) (VI)

If for R a benzyl radicle could be introduced in which there are
nethoxyl groups present the resulting compounds ought to be
nearly related to the alkaloids laudanosine, papaverine, hydrastine
and narcotine. For this reason attempts were made to obtain such
compounds as contain a benzyl group with one or more CH3.0
groups. According to Blaise (Compt. rend. T32, 38; 133, 299) cyan-
ides react with organometallic compounds forming addition products
which are decomposed by water into imido compounds. The imido-
compounds are then easily converted into the corresponding ketones.
/ * R’ A
R.C.; N +'.Mg.Hlg= —R.C — R.C. ...— R.C.
NH O
/
\N,MgHig
Hence it was expected that cyano-cotarnine would react with
p-methoxyphenyl magnesium iodide, CH3.O.C6H4.Mg. I, in the follow
ing way:
36
C6H 1.O.CH3
/
(SN } = N.Mg.I
(H3.() | CH3. O
N CH-N.CH3 –——) N CH-N.CH3 —— »
((H2O2) = Co H 3 | (CH2O2) = C6H 3 |
CH2.CH2 CH2, CH2
Cyanocotal’nine.
CoEI.1.0.0H8 C6H4.O.CH3
/ /
C = NH C = O
—— ) CH3.O | ) CH3. O |
N CH-N.('H3 N CH-N.CH3
(CH2O2)= C6H 3 | (CH2.02) = C6H 3 |
CH2. CH2 CH2. CH2
Experiment showed, however, that by the action of Grignard's
solutions upon cyanocotarmine the cyanogen group is split off and
the products of the reaction are the same as when cotarnine itself
is used. This behavior of cyanocotarnine would seem to indicate
that the cyanogen group is not linked to carbon as in Ordinary
cyanides but is linked to nitrogen. Hence of the two formulas pro-
posed for cyanocotarnine (Ber. 1900, 383).
CH3. O CH.CN CH3. O ºn
ZN /N - /N / CN
o, Nº NN.ch, o/ NZ N Nº.
CH2( and CH2( ſº CH3
O /N /CH2 ON / /CH2
Y Yá º
the second one must be the correct one. The reaction of cyano-
cotarnine with Grignard's solutions would then be similar to that
of alkylidene bases (Ber. 1904, 2691) consisting in first forming an
addition product which is decomposed by the water with elimination
of hydrocyanic acid.
º (H.R. ſo. II - CII.3.() (;II. IR
N / Mg.IIlg. /N
o/ sº NN–CN () / ``Nch,
CH2/ N(;His CHA’ | | ().H.
-\ | -|- II 2 () = *N | + HCN + Mg 2+
O /\ you. o º CH2 H]g.
CI 1.2 (XH2
37
That this interpretation of the reaction of cyanocotarnine with
Grignard's solutions is right is shown by the fact that the same
products are formed from cotarnine hydrochloride whose formula is
similar to the second formula of cyanocotarmine. In this case, too,
the product is the same as that which is obtained from cotarnine
itself and hydrochloric acid is eliminated.
CH3. O can Mo'. H CH3.0 CH.R.
N / Mg. Hig. % N. / .
o/ N/ NN-ºl. o/ / N.cii,
CH2( J NCH3 +ho-º. + HCl + Mg on
ov N /CH2 ON / /CH2 Hlg.
/ `ſ / ºf
The authors have further tried to substitute in the preparation
of Grignard’s solutions polyhalogen derivatives of hydrocarbons for
monohalogen derivatives and bring these solutions into reaction
with cotarnine expecting to obtain compounds of following con-
stitution where R'' devotes a divalent radicle like CH2, C2H4,
CºEI50H, etc.
CH3. (). CH R” CH (). CH3
2 / / N
o/ ``Neil, CIH3.N/ \,, No
CH2( | | | | | CH,
*\ | | | | | y ----
O /N /CH2 II2CN /N O
N / NZ * N/ N
CH2 CH2
It was found that though contrary to the statements of Grignard
and Tissier (Compt. rend. 132, 836) the polyhalogen derivatives of
hydrocarbons form compounds with magnesium in ethereal solution
similar to those obtained from monohalogen derivatives, the pro-
duct obtained from the action on cotarnine of such Grignard’s solu-
tions as are made from the polyhalogen derivatives does not consist
of two hydrocotarnine residues linked by a divalent radicle. The
product has the formula, C24H2s N2O6, and seems to consist of two
residues of hydrocotarnine directly linked to each other without the
introduction of a divalent radicle. If this is so the product can be
called di-hydrocotarnine and might have the following constitution: .
38
CH3. O CH CH O.CH3
o/~/~sch, ch,N'``No
º, 0. º H2ON º º
N/ Yº, Yſ. Nº

-Di-hydrocotarnine.
The formation of a-di-hydrocotarnine under these conditions .
would therefore be similar to the formation of pinacolines from alde-
hydes, the reaction consisting in a reduction of cotarnine to di-
hydrocotarnine. The a-di-hydrocotarnine is isomeric with a com-
pound previously obtained by Bandow (Ber. 1897, 1745) by the
action of sulphuric acid upon hydrocotarnine. That Grignard’s so-
lutions sometimes act as reducing agents has been observed by other
investigators (Chem. Centr. 1905, II, 752; Ber. 1905). It is remark-
able though that other reducing agents generally do not convert
cotarnine into a di-hydrocotarnine. On the other hand, not all
Grignard’s solutions made from monohalogen derivatives of hydro-
carbons convert cotarnine into a-derivatives of hydrocotarnine as
shown above. The Grignard’s solutions made, for example, from
piperonyl chloride or allyl iodide also convert cotarnine into a-di-
hydrocotarnine. Most probably there is formed in this reaction
diallyl or a substituded dibenzyl, CH2:02:06 H3 CH2.0H2.06H3:02:0H2
CH3.O
/ II.N.CH3
N | | + 2C3H5.Mg.I
ON- N |
N / CH2(H2
CH3. O CH CH O.CHs
o/\/\nch, ch, N/\/\o
CH2( | | | | | >UH, 4


| | | |
º * /\!/o
2
CH2
C3H5
+ | + 2 HO.Mg.I +
Cs H5
39
The assumption that the base, C24H23N2O6, is an a-di-hydro-
reotarnine of the above constitution is not in accord with the fact
that when treated with methyl iodide only one molecule-of the latter
is taken up instead of two. The resulting monoiodomethylate still
has basic properties and forms a crystalline acetate. This behavior
of the base will have to be cleared up by further experiments.
The following compounds were prepared during this investiga-
tion :
a-ETHYLHYDROCOTARNINE. This was prepared by treating cotar-
nine with ethyl iodide and magnesium in presence of ether. The re-
action takes place with evolution of heat and formation of a gas
which seems to be ethane formed from the group .NH.CH3 and
Grignard's solution . .N.H.CH3 + Mg.02H5.I = .N.CH3. Mg.I + C2H6.
Unless a large excess of Grignard’s solution is taken only half of
the cotarnine taken is converted into ethylhydrocotarnine, the other
half remains unchanged as a viscous mass insoluble in ether. The
new base is soluble in most organic solvents and is precipitated from
the solutions of its salts by sodium carbonate as an oily liquid
which soon becomes crystalline. A hydrochloride of a-ethylhydro-
cotarnine, C14H19NO3.HCl, was prepared by passing hydrochloric
acid gas into an etheral solution of the base. The salt is easily
soluble in water and remains after evaporation of the solvent, as a
syrupy mass which assumes crystalline form upon long standing.
A bichromate and an iodomethylate of a-ethylhydrocotarmine
were also prepared. The iodomethylate is not attacked by boiling
with concentrated alkalies.
On exposing powdered a-ethylhydrocotarnine to the action of
bromine vapors and digesting the product with alcohol a hydro-
bromide of monobrom a-ethylhydrocotarnine was obtained from
which the free base was obtained by means of sodium carbonate.
CH3. O CH.C2H5
o/ `sch,
/* |
!,
"Nº. \º CH2
Bl' CH2
Monobrom-0-ethyl-hydrocotarnine.
40
That the brominated base has this constitution was shown by
the fact that the same brominated base was formed by treating ,
monobromeotarnine with ethylmagnesium iodide.
ANIMO-OxIDE OF a-ETHYLHYDROCOTARNINE. This compound (VI)
was obtained by treating an acetone solution of a-ethylhydrocotar-
nine with hydrogen peroxide (30%), and, after removal of the sol-
vent, converting the oily residue into a platinum salt.
The same a-ethylhydrocotarnine in the form of a hydriodide was
prepared by treating cyanocotarnine with ethylmagnesium iodide in
ethereal solution and decomposing the product with water. The
yield is almost quantitative.
a-Propylhydrocotarnine was made by a method similar to the
one used for the ethyl compound. It can be recrystallized from
ligroin and forms a syrupy hydrochloride, a crystalline hydriodide
and an iodomethylate. The latter is not attacked by boiling with
strong acids or alkalies.
a-Isopropylhyhrocotarnine was prepared by boiling isopropyl
iodide and magnesium with absolute ether for 5–6 hours, then
digesting the solution with cotarnine for some time and decomposing
the product with water. The isopropyl compound is an oily liquid
which forms a crystalline hydriodide, a crystalline iodomethylate
and syrupy salts with hydrochloric, hydrobromic and sulphuric
acids. -
In the same way was prepared a-isobutylhydrocotarnine and
some of its salts.
a-Phenylhydrocotarnine was made either from cotarnine hydro-
chloride or cotarnine cyanide. The Grignard’s solution was prepared
from iodobenzol and magnesium. In the same way were prepared
a-paramethoxyphenylhydrocotarnine, a-naphtylhydrocotarnine and
a-benzylhydrocotarmine. The Grignard's solutions for these com-
pounds were prepared from magnesium and paraiodoanisol, a-brom.
naphtalin and benzylchloride respectively.
a-Di-hydrocotarnine was obtained from cotarnine and Grignard’s
solutions for the preparation of which was used either of the follow-
ing compounds: acetylene tetrabromide, allyl iodide, methylene
chloride, benzal chloride, ethylene bromide and piperonyl chloride.
The o-di-hydrocotarmine forms a monoiodomethylate which gives a
crystalline acetate when treated with dilute acetic acid. The di-hydro-
compound also forms crystalline Salts with several acids.
41
Attempts to bring cotarnine into reaction with Grignard’s solu
tions prepared from ortho-nitrobenzyl chloride or iodide or para-
cyanobenzyl chloride were not successful. The latter does not react
at all with magnesium and the former while reacting with magnesium
give a solution which does not react with cotarnine.
The new compounds here described were tested physiologically
and found to be very active. (Ber. 1906, 352.)
Cytisine.
M. Freund and P. Horkheimer have made a number of deri-
vatives of cytisine. On treating the alkaloid with nitrous acid two
isomeric nitro-nitrosocytisines are formed. One of them, a-nitro-
nitrosocytisine, is soluble in glacial acetic acid and alcohol, melts
at 244° and is identical with the compound previously prepared by
Partheil (Arch. d. Pharm. 232, 176), the other, 3-nitro-nitroso-
cytisine, is insoluble in alcohol and glacial acetic acid and melts at
275°. The amount of the a-compound formed in the reaction is
greater than the amount of the 3-compound. Being more basic
than the a-compound most of the 8-compound remains in the acid
mother liquors. From either of these nitro-nitrosocytisines the
nitroso group is eliminated by boiling with aqueous or alcoholic
hydrochloric acid (leaving the hydroehlorides of a- or 3-nitrocytisine
respectively from which the free a- or 3-nitrocytisine can be ob-
tained by means of alkali or alkaline carbonate in a Queous solution).
When a-nitro-nitrosoeytisine, C11H12N2O(NO2) (NO) is boiled
with aqueous hydrochloric acid (1.19) till the nitroso group is
eliminated and the resulting solution of a-nitrocytisine hydrochloride
treated with a solution of bromine in glacial acetic acid a perbromide
of monobromnitrocytisine hydrobromide is precipitated from which
the additive bromine can be removed either by means of sulphurous
acid or prolonged boiling with alcohol leaving the hydrobromide of
a-monobrom nitrocytisine, C11H12 Brn 2(NO2).H.Br.H2O. The free bro-
minated base can be obtained from the hydrobromide in crystalline
form by means of alkali or ammonia (alkali is to be preferred, am-
monia easily resinifying the substance). It is easily soluble in
alcohol but cannot be obtained in crystalline form from this solvent.
On prolonged drying it resinifies.
On adding potassium nitrite to a solution of monobrom nitro-
cytisine hydrobromide and then making the liquid alkaline with
42
ammonia a-nitro-nitrosobromcytisine is precipitated in crystalline
form and can be recrystallized from dilute alcohol.
On dissolving the free a-nitrobromcytisine in dilute hydrochloric
acid or boiling the a-nitro-nitrosobromcytisine with alcoholic hydro-
chloric acid the hydrochloride of a-nitrobromcytisine, C11 H12 BrN2O-
(NO2). HCl, can be obtained in crystalline form. The hydrochloride
melts above 290°. A nitrate of a-nitrobromcytisine was also pre-
pared.
When dibromcytisine is treated with nitric acid dibromnitroso-
cytisine, C11H11 Brº NaO2, is formed, not dibrom nitrocytisine, C11H11-
Br2N3O3, as had been supposed by A. Friedmann (Dissert. Berlin,
1901, 20). This was shown by the preparation of the same com-
pound from dibromcytisine hydrobromide by means of nitrous acid.
Both the solubilities and the melting points were in both cases
identical.
On reducing cytisine electrolytically in an apparatus described
by Tafel (Ber. 1900, 2214) it is converted into hydrodesoxycytisine,
C11H2ON2. *
C11 H14N2O + 8H = C11 H2ON2 + H2O
Unlike cytisine the hydro compound is volatile with steam and is
extremely easily soluble in water. It was purified by converting it
into the hydrochloride, then liberating the free base by means of
caustic potash in presence of very little water, shaking out the liquid
with ether and distilling the hydrodesoxycytisine in a current of
hydrogen. The base is an oily liquid of a strong spermine-like odor
boiling at 270° and has, a strong alkaline reaction (attracting
carbon dioxide from the air). The hydrochloride of hydrodesoxy-
cytisine is very easily soluble in water, difficultly soluble in alcohol
and is extremely stable towards acids, not being affected by heating
with fuming hydrochloric acid under pressure or with sulphuric acid
nearly to boiling.
By treating the hydrochloride of hydrodesoxycytisine with nitrous
acid in the cold or boiling it with strong nitric acid and then mak-
ing the liquid alkaline with ammonia nitrosohydrodesoxycytisine is
precipitated in crystalline form. The entrance of one nitroso group
into hydrodesoxycytisine shows that the free base must have the
formula, N.; C11H19: NH. In both cytisine and hydrodesoxycytisine
the second nitrogen atom is, therefore, tertiary.
On adding a slight excess of phenyl-mustard oil to free hydro-
43
desoxycytisine only the imido group goes into reaction forming the
following compound:
N i C11H19: N.C.S.NH Cohſ;
Wh in hydrodesoxycytisine is treated with methyl iodide in
ethereal solution the hydriodide of N-methylhydrodesoxycytisine,
N; C11H19N(CH3). HI, is formed. Even in presence of excess of methyl
iodide only one methyl group enters into the molecule (compare
Horkheimer, Dissert. Berlin, 1905). Alkali liberates from the
hydriodide free N-methylhydrodesoxycytisine as an oily liquid vola-
tile with steam and regenerating the same hydriodide when treated
with hydriodic acid. &
Methyliodide in ethereal solution when shaken with N-methyl-
hydrodesoxycytisine converts the latter into its iodomethylate,
' N; C11H19 N(CH3)2L. The same compound can be made from the
hydrochloride of hydrodesoxycytisine by the following method. The
hydrochloride is dissolved in warm alcohol, to the solution is added
the theoretical amount of sodium ethylate and, without the filtering
off from the sodium chloride, the liquid digested with one molecule
of methyl iodide for 24 hours. The liquid containing the hydriodide
of N-methylhydrodesoxycytisine in solution is then again treated
with theoretical quantities of sodium ethylate and methyl iodide
and, after standing 5–6 hours, the sodium chloride and iodide
removed by filtration. On evaporating the alcohol and recrystallizing
the residue from hot water the iodomethylate of N-methylhydro-
desoxycytisine is obtained in beautiful, anhydrous crystals. The
iodomethylate still possesses basic properties, being easily soluble in
dilute hydrochloric acid and reprecipitable from such solution by
ammonia. The second, tertiary nitrogen atom of cytisine could not
be made to combine with methyl iodide even in the heat and under
pressure. *
The iodomethylate is not affected even by boiling with strong
alkali crystallizing out unchanged on cooling the liquid, but if it is
converted into the ammonium hydroxide base by means of silver
hydroxide and, then, after strong concentration of the liquid, the
ammonium base warmed with strong potassium hydroxide, des-N-
dimethylhydrodesoxycytisine, N.; C11 H18.N(CH3)2, separates out as
an oily liquid of a yellowish color. The oily des-base was taken up
with ether and the ethereal solution subjected to distillation after
drying it with solid potassium hydroxide. The base boils at 266 to
44
268° and forms easily soluble salts with acids which could not be
obtained in crystalline form.
While in hydrodesoxycytisine only that nitrogen atom which
makes up the imido group is capable of reacting with methyl
iodide giving either the hydriodide of methylhydrodesoxycytisine,
N; C11H19: N.CH3. HI, or the iodomethylate of methylhydrodesoxy-
cytisine, N: C11H10: N(CH3)2 I, in des-N-dimethylhydrodesoxycytisine,
both nitrogen atoms can react with methyl iodide. On digesting
the des-base with excess of methyl iodide in ethereal solution for 14
days the diiodomethylate of the des-base is formed, ICH3.N C11H18:-
N(CH3)31, and can be recrystallized from hot absolute alcohol to
which a trace of water is added or from a little water to which some
potassium hydroxide is added. But on digesting the des-base with
only one molecule of methyl iodide for 24 hours the monoiodo-'
methylate, (CH3)2.N.C11H1sN)0H8)I, is formed, though contaminated
with other iodomethylates. These were removed by distilling the
mixture with concentrated potassium hydroxide which decomposes
them into trimethylamine and an oily liquid having the odor of
conine; the monoiodomethylate of the des-base remains as a crystal-
line mass floating on the alkaline liquid in the distilling flask and
can be recrystallized from alcohol.
When an excess of a solution of bromine in glacial acetic acid
is added to a solution of hydrodesoxycytisine hydrochloride in the
same solvent and the mixture warmed on the water bath a per-
bromide is precipitated which filtered off from the liquid and digested
with hot alcohol is soon converted into a dilly drobromide of a
monobrominated base, C11H17Br M22H Br. The dihydrobromide can
be recrystallized from absolute alcohol or hydrobromic acid. When
recrystallized from water it seems to undergo some change shown
by the constant rise of the melting point after each recrystallization.
The free brominated base underlying the dihydrobromide could not
be obtained. (Ber. 1906, 814.)
Ephedrine.
E. Schmidt and his collaborators continue the investigation Of
ephedrine and pseudoephedrine. In a previous paper (Arch. Pharm.
1904) it was shown that when ephedrine is heated to 170°–180°
with hydrochloric acid of 5 per cent. it is converted into the isomeric
pseudoephedrine and that pseudoephedrine is identical with Nagai's
45
isophedrine. This conversion of ephedrine into pseudoephedrine can
be accomplished with greater facility by heating the alkaloid for 12
hours on a water bath with hydrochloric acid of 25 per cent. The
conversion is not complete, a state of equilibrium establishing itself
between the two bases. The conversion of the laevorotatory pseudo-
ephedrine is accompanied by a change of place of the OH group.
This is shown by the fact that the unsaturated alcohol Co Ho. OH
obtained by exhaustive methylation of ephedrine differs considerably
from the alcohol of the same formula obtained from pseudoephedrine.
Hence the two are structurally, not only optically, isomeric.
(Arch. d. Pharm., 1906, 239.)
H. Emde has investigated the conversion of ephedrine, C10H15NO,
into its isomeride pseudoephedrine which takes place when the former
is heated with hydrochloric acid (see preceding paragraph). The
unchanged ephedrine is separated from the pseudoephedrine by re-
crystallization from alcohol and precipitation with sodium carbonate
which does not precipitate ephedrine. The identification of the two
bases was made by means of their crystallographic forms and optical
rotation. As in the conversion of ephedrine into pseudoephedrine
no racemic compound is formed and the rotation to the right of
pseudoephedrine is considerably greater than the rotation to the
left of ephedrine the difference between the two alkaloids cannot be
of a sterochemical nature but must be due to a difference in the
position of the OH group.
When ephedrine is heated by itself or with alkalies it undergoes
a change which will be investigated later.
On warming pseudoephedrine with methyl iodide it is partly
converted into methylpseudoephedrine, C16 H14(CH3)NO, which could
not be obtained in crystalline condition. It was analyzed as a
chloraurate. By heating methylpseudoephedrine with more methyl
iodide it is converted into the iodomethylate of methylpseudo-
ephedrine, C10H14(CH3)N.CH3]. When heated with an excess of
methyl iodide pseudoephedrine is converted into a mixture of tertiary
methylpseudoephedrine and quaternary methylpseudoephedrine iodo-
methylate. To separate the two the iodides are dissolved in water
and the solution treated with silver oxide. The quaternary base
remains in solution while the tertiary base is precipitated together
with the silver iodide from which it can be separated by means of
ether. A comparison of methylpseudoephedrine and its iodomethylate
46
with the corresponding compounds obtained from ephedrine showed
that they were not identical.
On distilling a solution of methylpseudoephedrine methyl
hydroxide it is decomposed into trimethylamine and an alcohol
which is isomeric with cinnamic alcohol
C9. H10(OH) N(CH3)2 O II = Co FIo. OH + (CH3)3 N + H2O.
(Arch. d. Pharm., 1906, 241.)
Ergotiuille.
G. Barger and F. H. Carr have analyzed crystalline ergotinine
and found that the figures obtained by Tanret for the percentage
of carbon and hydrogen are correct but that Tanret's figures for
nitrogen are too low. They find 11.7 instead of 9 per cent nitrogen.
That their nitrogen was free from methane was shown by P. Haas.
Molecular weight estimations in phenol by the cryoscopic method
gave the values 477 and 516; in pyridine solution the value 463
was obtained employing a microscopic vapor pressure method of
G. Barger. The formula of ergotinine (crystalline) would therefore
seem to be C2s H32N4O4 = 488. Ergotinine does not contain phenolic
OH or methoxyl groups. Dissolved in methyl iodide a gelatinous
methiodide is formed and with bromine in chloroformic solution a
hydrobromide of monobromergotinine seems to formed. The authors
have obtained amorphous ergotinine in pure condition and prepared
several crystalline salts of the alkaloid. For this alkaloid they
propose the name ergo toxine. Unlike crystalline ergotinine, ergo-
toxine is easily soluble in aqueous so lium hydroxide and gives a
benzoyl derivative. Both alkaloids give strongly fluorescent solu-
tions, and give with sulphuric acid and ferric chloride the play of
colors originally described by Keller: According to physiological
experiments of H. H. Dale ergo toxine seems to be the chief active
principle of the drug, crystallized ergotinine being almost or quite
inactive. (Pharm. J., 1906, v. 23, 257.)
C. Tanret offers the following criticisms on the work of Barger
and Carr on ergotinine (see preceding paragraph.)
I. The reason for the low percentage of nitrogen found by
Tanret in ergotiline is due to the fact of his having used Will and
Warrentrap's method while Barger and Carr used Dumas' method
At the time he published his work Will and Warrentrap's method
47
was considered very reliable. On now repeating the analysis by
Dumas' method the author finds Barger and Carr's figures correct.
II. The determination of the molecular weight of ergotinine by
the freezing method with phenol as a solvent carried out by Barger
and Carr the author considers unreliable owing to the formation of
a phenolate. That the phenol really forms a phenolate of the alka-
loid and does not act simply as a solvent is shown by a comparison
of the optical rotation of ergotinine dissolved in pure chloroform,
and the rotation of a solution of an equal amount of the alkaloid
in phenol which is afterward gradually diluted with chloroform to
the same concentration as the simple chloroform solution. As the
phenol-chloroform solution has a lower rotation than the chloro-
formic solution and the rotation is still further lowered by gradual
addition of chloroform we must assume the formation of a phenolate.
If the lowering were due simply to the action of phenol as a solvent
the further addition of chloroform overcoming more and more the
action of the phenol ought to gradually raise the rotation.
The other method of molecular weight determination used by
Barger and Carr (employing a microscopic vapor pressure), giving
the same results as the phenol method, is clearly also unreliable. -
III. The formula, Cash40Ns0s, suggested by Tanret is more in
accord with the results of the analyses of ergotinine and its salts
than the formula of Barger & Carr, C2s H32N4O4.
- IV. As the name amorphous ergotinine was given to the amor-
phous alkaloid present in ergot by the discoverer, Tanret, it is not
right for Barger and Carr to change that name to ergotoxine until
it can be shown that the amorphous alkaloid really differs in com-
position from crystallized ergotinine. - -
W. The statement of Barger and Carr that amorphous ergotinine
(which they call ergotoxine) differs from crystallized ergotinine in
being soluble in excess of sodium hydroxide is wrong. Both ergoti-
nines are according to the author soluble in excess of alkali.
WI. That amorphous ergotinine is very active physiologically
the author admits but the statement of Barger and Carr that
crystallized ergotinine is perfectly inactive the author considers to
be not in accord with the Opinion of the medical profession (see the
author's article in J. pharm. chim., 1885, 3, 19).
(J. pharm. chim., 1906, 397.)

48
Ergot.
F. Kraft has investigated the constituents of the ideoleated
extract of ergot. The constituents found were as follows: ergosterin
20 per cent., alkaloids 41.3 p. c., secalonic acid 3.5 p. c., amorphous
yellow acids 9.7 p. c., oil 17 p. e., residue not investigated 2 p. c.,
loss 5.6 p. c. The extract was prepared by shaking powdered ergot
with ether and water, drawing off the ethereal liquid and distilling
off the solvent. The extract is then mixed with petroleum ether and
the flocculent precipitate filtered off. The amount of this deoleated
precipitate was about 0.5 per cent. of the ergot taken. On now
treating the deoleated extract again with hot ether most of it goes
in solution leaving ergosterin behind. The ergosterin can be re-
crystallized from methyl alcohol. A hot alcoholic "solution of
ergosterin gelatinizes on cooling.
The alkaloids of ergot exist in the plant in the free condition
and can therefore be extracted with ether without the use of alkali.
The amount of alkaloids present in good ergot is about 2 to 2.5
per cent. They are best prepared as follows. The ethereal extract
of ergot is shaken out repeatedly with a weak solution of tartaric
acid and the alkaloids precipitated with sodium carbonate. Owing
to the difficult solubility of the salts of the ergot alkaloids with in-
Organic acids these acids are not suitable for extracting the alkaloids.
By dissolving the crude alkaloids in glacial acetic acid, diluting with
water and adding sodium sulphate the mixture of alkaloids was
decomposed into ergotinine sulphate and a sulphate of a new alka-
loid named hydroergotinine. The hydroergotinine sulphate being
considerably less soluble than ergotinine sulphate separates out first.
From the sulphates ergotinine and hydroergotinine were obtained
by making alkaline with sodium carbonate. Ergotinine is crystal-
line, becomes brown at 210°, melts at 219° and is not affected by
exposure to light. It is not converted by heat into the amorphous
alkaloid as has been claimed. In dry condition both ergotinine and
hydroergotinine are quite stable. Heat and chemical reagents de-
compose them into black or amorphous substances. Each solution
of the alkaloids in glacial acetic acid and precipitation with ammonia
or sodium carbonate is accompanied by partial decomposition.
Hydroergotinine is amorphous and is more easily soluble in
most solvents than ergotinine. In cold alcohols hydroergotinine is
soluble in all proportions while ergotinine requires about 70 parts
49
of hot methyl or ethyl alcohol and most of it separates out on
cooling. The sulphate of hydroergotinine requires about 8000 parts
of water for solution while ergotinine sulphate is soluble in about
500 parts.
Hydroergotinine seems to be a hydrate of ergotinine. The two
bases are mutually convertible into each other. On boiling hydro-
ergotinine with methyl alcohol it is completely converted into
ergotinine which crystallizes out on cooling. The same conversion
of amorphous hydroergotinine into crystalline ergotinine takes place
also when the solution of the former in dilute acetic acid is boiled
for some time but in this case the ergotinine is accompanied by
decomposition products. On the other hand when ergotinine is
digested with cold dilute acetic acid it is gradually changed into
hydroergotinine. A freshly prepared solution of ergotinine in dilute
acetic acid is not precipitated upon addition of sodium sulphate,
after 10 days’ standing sodium sulphate produces a heavy precipitate
of hydroergotinine sulphate.
Besides ergotinine and hydroergotinine ergot also contains two
soluble bases, betaine and choline. These were isolated by Jahn's
method (Arch. d. Pharm., 135, 152) and separated from each other
in the form of hydrochlorides by means of absolute alcohol in which
choline hydrochloride is almost insoluble.
The ergotinic acid described by Kobert (Arch. f. exp. Path. u.
Pharm. Bd. 18) was found to be a mixture of various substances
from which were isolated mannite and an acid named secaleamido-
sulphonic acid,
NH2
Clshazoº
SO3H
The acid is precipitated by potassium bismuth iodide, is easily
soluble in water with an intense acid reaction but insoluble in or-
ganic solvents. It precipitates silver nitrate in ammoniacal solution
but does not reduce it even in the heat. It melts at 200°. It does
not give the sulphuric acid reaction unless it is melted with sodium
carbonate and saltpetre when it shows the presence of both sulphate
and sulphite. Hence the sulphur must be in form of an SO2OH
group which would account for the strong acid reaction. When
treated with nitrous acid it does not form a diazo compound but
gives off nitrogen. Hence it must contain an alipathic NH2 group.
Physiological experiments showed that the deoleated ethereal
50
extract of ergot had the characteristic action of ergot, i. e. conti ac-
tion of the uterus. This action is due to some substance present in
the extract but the substance could not be isolated. The pure sub-
stances obtained from this extract have entirely different physio-
logical effects. The acids are inert. The alkaloids are strong poisons
and exert only an injurious influence upon the system. Hence the
value of a sample of ergot does not depend upon the amount of
alkaloids it contains. (Arch. Pharm., 1906, 336.)
Ergot Alkaloids.
According to G. Barger and H. H. Dale the amorphous alkaloid
of ergot which was named by Kraft (Arch. Pharm., 1906, 336)
hydroergotinine is identical with the substance previously prepared
and named by them ergotoxine. They do not agree with Kraft who
considers hydroergotinine (ergotoxine) to be a hydrate of ergotinine
but suppose that ergotinine is an acetyl derivative of ergotoxine.
The physiological effects of most ergot preparations are to a great
extent due to ergotoxine. The name hydroergotinine should be
dropped. (Arch. Pharm., 1906, 550.)
Hordenine.
A new alkaloid, hordenine, was isolated by E. Léger from malt
germs by Stas' method. The yield of alkaloid seems to vary with
the temperature at which the malt had been dried. The alkaloid
crystallizes in voluminous, strongly doubly refracting prisms and
has the formula, C10H15NO. It melts at 117.8°, sublimes at 140°
to 150°, is optically inactive and is easily soluble in alcohol ether
and chloroform. It is only slightly soluble in water, hot carbon
tetrachloride, benzol or petroleum ether. It is strongly alkaline to-
wards litmus and phenolphthalein, liberates ammonia from its salts
and is not attacked by concentrated sulphuric acid or by fused
potassium hydroxide. It reduces ammoniacal silver nitrate and
potassium permanganate and liberates iodine from iodic acid. It
forms crystalline salts with acids and an iodomethylate having the
formula C10H15NO.CH3 I. Hence it is a tertiary base. As it forms
an acetyl derivative, C19H 14NO(CH3CO), having basic properties it
must contain a phenolic OH group. (Bull. soc. chim., 1906, 235).
E. Léger has investigated the constitution of hordenine. The
alkaloid is isomeric but cannot be identical with the natural and
artificial ephedrines which were prepared by Fourneau (Bull. Soc.
51
chim. [3], 35, 285). It differs from the optically active natural
ephedrines which are secondary bases in being optically inactive and
having the character of a tertiary base. It also differs from the
liquid artificial ephedrines which are amino alcohols in being a cry-
stalline amino phenol. &
Potassium permanganate oxidizes hordenine almost entirely to
oxalic acid; only a very small amount of another acid could be
isolated which was colored violet by ferric chloride.
Hot nitric acid oxidizes hordenine to picric acid and oxalic acid.
The picric acid was identified by the solubility and crystalline form
of the potassium salt and by the purple color developed on boiling
the acid with potassium cyanide.
On converting the iodomethylate of hordenine into the corre-
sponding methyl hydroxide by means of silver oxide and distilling
the ammonium base three substances were obtained : trimethylamine,
a colorless oily liquid heavier than water and of an agreeable odor,
and an amorphous compound of a phenolic character. “
The formation of picric acid from hordenime shows that the
alkaloid must be a derivative of benzene and contains a phenolic
OH group while the formation of trimethylamine from hordenine
iodomethylate shows that there is in the alkaloid a (CH3)2N group.
Hence the nitrogen atom does not belong to a pyridine nucleus.
That hordenine is not a derivative of dimethylaniline is shown by
the fact that the latter is a very weak base and the presence of an
OH group would diminish still more the basicity of an oxydimethyl
aniline while as a matter of fact, hord, nine is a very strong base
reddening phenolphthalein and driving out ammonia in the cold
from its salts. Hence the nitrogen atom in hordenine must be linked
to the benzene ring by means of a chain of one or more carbon atoms
giving a compound of following formula:
/ CH2CH2—N(CH3)2
C
*E.
OH
That the formula is not
CH2—N(CH3)2
C6H3–OH
CH3
*~~
52
is shown by the fact that nitric acid oxidizes the alkaloid to picric
acid, not to trinitro cresol which is obtained by nitrating cresol.
(Bull. soc. chim., 1906, 868.)
G. Otto Gaebel investigated the constitution of hordenine. The
isolation of the alkaloid was carried out by the following method: The
malt was extracted with hot alcohol for two days, the cooled alcoholic
extract filtered, concentrated to syrupy consistence, mixed with water
and again filtered. After adding potassium carbonate the filtrate
was shaken out once with a small amount of ether which removed
a colored substance and then repeatedly with larger quantities of
ether to extract the alkaloid. The ethereal solution, dried with
potassium carbonate, leaves on evaporation crystals of hordenine
which can be purified by means of animal charcoal in ethereal solu-
tion. The yield was about 0.2%.
Hordenine is soluble both in alkalies and acids, reacts with
Millon’s and Piria's reagents and is precipitated by alkaloidal re-
agents. As was shown by Léger (Compt. rend., 142, 108) hordenine
is a tertiary base and has a phenolic character. Its formula is
C10H15NO. Fusion with potassium hydroxide does not affect it but
potassium permanganate oxidizes it completely unless the OH group
is protected by methylation. The methylation was accomplished by
shaking the alkaline solution of hordenine with dimethyl sulphate.
On oxidizing the resulting methyl derivative with potassium per-
manganate in alkaline solution at water bath heat it is converted
into anisic acid. When subjected to exhaustive methylation horde-
nine breaks up into several products one of which could be identified
as trimethylamine. From these results the author draws the con-
clusion that the formula of hordenine is as follows:
OH
/N
( )
| |
CH2—CH2.N(CH3)2
(Arch. Pharm., 1906, 435.)
Metanicotine.
E. Maass and A. Hildebrandt find that when metanicotine is
reduced with sodium and absolute alcohol the product is not as
53
previously (Ber. 1905, 1831) reported hexahydrometanicotine but a
mixture of hexa- and octo-hydrometanicotine which can be separated
from each other by distillation with steam. The constitution of the
bases and their relation to metanicotine is shown by the following
formulas:
HC CH2 HC CH2
R. T. Jº,
N
HC/ Nc H2C/ NCH
| HC CH2 HC CH2
HCN CH NH.CH3 H2CN CH2 NH.CH3
J/ V/
N NH
Metanicotine. Hexahydrometanicotine.
H2(! CH2
hº NCH
| H2C /CH2


Octobydrometanicotine.
The octohydrometanicotine is identical with the octobydronicotine
previously obtained by Blau in the reduction of nicotine. The latter
compound though obtained from nicotine must also be looked upon
as a derivative of metanicotine for the leason that the ecto com-
pound boils at a temperature higher than the boiling point of nico-
tine but lower than that of metanicotine and it is well known that
reduced substances generally boil below the boiling points of the
substances from which they are obtained by reduction.
The metanicotine used for this work was obtained by a slight
modification of Pinner’s method (Ber. 1894, 1053). After reduction
with sodium and absolute alcohol the product was fractionally
distilled with steam, the fractions of the distillate acidulated with
hydrochloric acid and, after concentrating to a syrup, the residue
spread on porous plates. Part of the thick liquid was absorbed by
the plates while another part remained as a crystalline powder. On
decomposing the crystalline powder with sodium hydroxide and
distilling the oily liquid which separated out the octohydrometa-
nicotine distilled over at 258.5–260°.
54
The porous plates were then powdered and extracted with hot
alcohol. After distilling off the alcohol, the residue was dissolved in
water and the liquid shaken out with ether after adding sodium
hydroxide. After removal of the ether and distilling the residue the
hexahydrometanicotine passed over at 24.8—250°.
Hexahydrometanicotine, C10H2ON2, is a colorless oil boiling at
248—250°, having an odor like piperidine, becoming yellow on
standing and emitting vapors that irritate the respiratory Organs.
It is easily soluble in alcohol or ether but insoluble in water. It is
optically inactive and at 20° has a specific gravity of 0.9578 com-
pared with water at 4°. g
The hydrochloride of hexahydrometanicotine, C10H2ON2.2HCl is
a very viscous hygroscopic oil that cannot be obtained in crystalline
form. It is easily soluble in water, alcohol and chloroform, difficultly
soluble in acetone but insoluble in ether or ligroin.
A chloroplatinate of hexahydrometanicotine, C10H2ON2.2HCl. PtCl4,
was prepared by adding an alcoholic solution of platinum tetra-
chloride to an alcoholic solution of the hydrochloride. It forms an
oily liquid which becomes solid when kept under absolute alcohol
but resinifies on drying on porous plates. Recrystallized from hot
water it forms yellowish-red prisms melting at 225° with decompo-
sition.
A chloraurate of hex hydrometanicotine could not be obtained in
crystalline form. It is precipitated from water as an oily liquid
which is soluble in alcohol but insoluble in water, acetone or ligroin.
Octobydrometanicotine, C10H22N2, is a colorless oil boiling at
258.5–260° and having a penetrating odor. It is easily soluble in
water but separates out again on the addition of alkali. It is
optically inactive and at 20° has a specific gravity of 0.9173 com-
pared with water at 4°.
A hydrochloride of Octobydrometanicotine, C10H22N2.2HCl, was
prepared by adding hydrochloric acid to an aqueous solution of the
base and evaporating the liquid to dryness. It was purified by
treating it with acetone to dissolve resinous matter and recrystalliz-
ing from water. The salt is easily soluble in water, a little less
soluble in alcohol and insoluble in ether, acetone or ligroin. It
melts at 202°.
A chloroplatinate, C10H22N2.2HCl, PtCl4, was made by treating
the alcoholic solution of the hydrochloride with an alcoholic solution
55
of platinum tetrachloride and rubbing up the oily double salt with
absolute alcohol. Recrystallized from water it forms dark red crys-
tals melting at 202.5°. *
A chloraurate, C10H22N2.2HCl.2AuCl2, was prepared by adding
an alcoholic solution of gold chloride to an alcoholic solution of
the hydrochloride and recrystallizing the double salt from dilute
alcohol. The chloraurate forms yellow leaflets melting at 142° with-
out decomposition. It is soluble in ether and alcohol but insoluble
in water, acetone and ligroin. (Ber 1906, 3697.)
Methylmorphimethille.
According to R. Pschorr, H. Roth and F. Tannhäuser a-methyl-
morphimethine is converted into 8-methylmorphimethine not only
by heating the former with potassium hydroxide in alcoholic solution
but even by heating the a-compound by itself in vacuum to about
220–240°. The identity of the 3-compound obtained by the authors'
method with the compound obtained by using alcoholic potassium
hydroxide was shown by a comparision of the benzoate and iodo-
methylate of which the former was made by boiling the 8-compound
with benzoic acid in solution in benzene and the latter by digesting
the 3-compound with methyl iodide in benzene. The benzoate was
purified by recrystallizing it from a mixture of alcohol and petroleum
ether. The iodomethylate was recrystallized from water.
(Ber. 1906, 19.)
Morphine.
J. C. Irvine finds that inactive lactic acid can be easily resolved
into the d- and l-acids by means of morphine, the morphine l-lactate
crystallizing quickly from dilute aqueous solutions while morphine
d-lactate crystallizes only after long standing in a vacuum desiccator.
By this method the yield of pure l lactic acid is almost quantitative
while the amount of lactic d-acid is about 50 per cent of theory. The
purity of the acids was established by the specific rotation of the
zinc salt and estimation of water of crystallization, but as the rota-
tion of the metallic lactates display small rotations in solution the
purity of the acids was also tested by converting them into methyl
lactate and afterward into methylic methoxypropionate (Trans.
1899, 75, 485), which has a specific rotation of 95.21°.
The d- and l-lactic acids were obtained by the zinc ammonium
salt method of resolution and the morphine salts prepared by neut-
56
ralizing hot aqueous solutions of the acids with the alkaloid. The
morphine l-lactate contains no water of crystallization and in 5 per
cent aqueous solution has a rotation [a]n 20= —91.8°.
The salt of the d-acid readily forms super-saturated solutions
and only crystallizes slowly in clusters of radiating prisms. It con-
tains a molecule of water of crystallization and in 5 per cent aqueous
solution has a specific rotation [a]p 20 = —92.7°.
The inactive lactic acid used for resolution by morphine was
syrupy and contained 23.2 per cent. of anhydride as was shown by
titration before and after hydrolysis. The acid was diluted to 8
times its volume with water and after boiling for six hours to
hydrolyze the anhydride the hot liquid was neutralized with mor-
phine. On cooling the salt of the l-acid crystallized out while the
salt of the d-acid remained as a syrupy liquid. The l-acid was liber-
ated from the morphine salt by ammonia and purified through the
calcium salt. From the caleium l-lactate the acid was set free by
oxalic acid and separated from traces of calcium oxalate by extrac-
tion with a mixture of alcohol and ether.
The l-acid was obtained as a colorless syrup and converted into
a zinc and a silver salt. By decomposing the latter with methyl
iodide a specimen of methylic l-lactate containing a small proportion
of methylic l-methoxypropionate was prepared. By the method
previously described (loc. cit.) this was converted into methylic
l-methoxypropionate and found to possess a rotation of [a]n 20 =
94.7°. The highest rotation recorded for this substance is [a]p 20 =
+ 95.5°.
In order to see whether the acid is not changed during the
methylation (Trans. 1901, 79, 972) the methylic l-methoxypropionate
was warmed with hydriodic acid at the lowest temperature at which
in a Zeisel apparatus silver iodide was deposited (85°) and, after
removal of the excess of hydriodic acid at 80° under reduced pressure
and converting the l-acid into a silver salt by means of silver oxide,
the silver salt was decomposed by sulphuretted hydrogen and the
liberated l-lactic acid converted into the zinc salt. Analysis of this
salt showed that no change in the configuration of the acid takes
place in the methylation.
The preparation of d-lactic acid from morphine d-lactate was
carried out exactly as described in the case of the l-acid. The d-acid
was analyzed as a zinc salt.
57
In connection with this work the author finds that although
active zinc lactate when crystallized in the usual manner readily
loses its water of crystallization at 110°, the residue left on evapor-
ating an aqueous solution of the salt on the waterbath does not
become completely anhydrous even at 150°.
(J. Chem. Soc., 1906, 935.)
According to L. Georges and Gascard small quantities of mor-
phine can be estimated colorimetrically by making use of the fact
that morphine liberates iodine from iodic acid coloring the liquid
yellow or reddish-yellow. Addition of ammonia to the liquid changes
the color to yellowish-brown. The estimation is carried out by com-
parison with solutions of morphine of known strength prepared
under identical conditions. (J. pharm. chim., 1906, 513.)
C. Mai and C. Rath have tried to make use of the color reactions
of morphine in order to devise a colorimetric method for the estima-
tion of very small quantities of this alkaloid. The liberation of
iodine from iodic acid and the deep violet color given by Froehde's
reagent are not suitable for this purpose. Better results were ob-
tained with Marquis’ reagent which will detect 0.00003 gram mor-
phine in 1 c. c. of liquid but the exact conditions for quantitative
work will be reported later on. (Arch. Pharm., 1906, 300.)
R. Pschorr finds that when morphine is digested with liquid
anhydrous hydrochloric or hydrobromic acid the alcoholic OH group
is replaced by Cl. The products are therefore identical with chloro-
or bromomorphide previously obtained by Schryver and Lees (J.
Chem...Soc., 1900, 1092) by the action of the halides of phosphorus
upon morphine. In chloromorphide or bromomorphide as well as in
chlorocodide and bromocodide (Ann., 210, 107; J. Chem. Soc., 1902,
563) the halogen is easily replaceable by radicals containing sulphur.
Thus with potassium sulphydrate a compound is formed which con-
tains an SH group instead of chlorine. This compound is then
oxidized to a dimolecular compound as follows:
2013 H2ONO2Cl + 2KSH —x [2013 H29 NO2. SHJ -- O – (C18H20 NO2.S.–)2
Chlorocodide. Bisthiomorphide.
lf instead of a sulphydrate an alkaline mercaptide be used alkyl-
thio derivatives are formed :
C18H29 NO2C) + NaSC2H5 = C1s H29NO2.SC2H5 + NaCl
Ethylthiocodide.
58
When the iodomethylate of chlorocodide is boiled with sodium
hydroxide both halogens are split off and instead of the correspond-
ing “methine” base, chloromethylmorphimethine, halogen free amor-
phous products are formed. The chloromethylmorphimethine can be
obtained in the form of a hydrochloride by the action of phosphorus
trichloride upon a-methylmorphimethine in chloroformic solution.
The decomposition products of chloromethylmorphimethine obtained
by boiling it with acetic anhydride are the same as those obtained
from a-methylmorphimethine, namely, acetylmethylmorphol, dimethyl-
oxethylamine and a base having the composition of tetramethyl-
ethylenediamine. The formation of acetylmethylmorphol from chloro-
methylmorphimethine shows that in the decomposition by means of
acetic anhydride the alcoholic hydroxyl, not the indifferent oxygen
atom is eliminated, as in the latter case from chloromethylmorphi-
methine containing a chlorine atom instead of the alcoholic OH
group there ought to be formed a chloroacetylmethylmorphol. It is
remarkable that among the decomposition products of chloromethyl-
morphimethine containing an N(CH3)2 group there is found mono-
methyloxethylamine, H.O.C2H4...N.H.CH3. If phosphorus trichloride
be made to react with a-methylmorphimethine in the absence of a
solvent the product consists of the hydrochloride of the phosphorous
acid ester of methylmorphimethine.
If instead of phosphorus trichloride phosphorus pentachloride be
made to react with a-methylmorphimethine a dichloride of methyl-
morphimethine, C19H23NO3Cl2, is formed which when decomposed
with acetic anhydride gives a derivative of trioxyphenanthrene
(diactoxymethoxyphenanthrene) together with the same bases that
are formed from chloromethylmorphimethine. The trioxyphenan-
threne derivative contains an acetoxy-group linked to one of the
two “bridge” carbon atoms of phenanthrene as upon oxidation it is
converted into 3-methoxy-4-acetoxyphenanthrenequinone. Judging
from the identity of the melting points the diacetoxymethoxyphenan-
threne seems to be identical with the compound obtained by Knorr
in the decomposition of oxycodeine C18H2ONO3(OH). The OH group
of the oxycodeine must therefore be at one of the “bridge” carbon
atoms.
The chloromorphide, C17H1sNO2Cl, was prepared by digesting
morphine for several days at ordinary temperature with anhydrous
liquid hydrochlorio acid in an explosion tube, evaporating the acid
j%)
and after adding excess of sodium bicarbonate extracting the chloro-
morphide with ether. After recrystallizing from methyl alcohol it
melts at 192° (corr.). The yield is about 40 per cent. of theory.
The chloromorphide was converted into an iodomethylate by warm-
ing it with methyl iodide. The iodomethylate melts at 207° (corr.).
Bromomorphide was obtained in the form of a hydrobromide by
treating morphine with liquid hydrobromic acid in presence of some
phosphorus tribromide. The hydrobromide melts at 196° with de-
composition. The free bromomorphide can be easily obtained from
the hydrobromide. The yield is about 65 per cent. The bromomor-
phide forms an iodomethylate melting at 200°.
On digesting bromomorphide with phenyl isocyanate in chloro-
formic solution the corresponding ester of phenylcarbamic acid is
formed, showing the presence of an OH group.
The bisthiomorphide, (C18H29 NO2.S.–)2, was prepared by boiling
chloro- or bromomorphide with aicoholic potassium sulphydrate,
diluting with water and after saturating with carbon dioxide extract-
ing with chloroform. The bisthiomorphide melts at 201°. When the
bisthiomorphide is methylated by means of sodium methylate and
methyl iodide it is converted into bisthiocodide iodomethylate. The
bisthiocodide underlying this iodomethylate can be prepared from
bromocodide (R. Fischer, Inaug. Diss., Berlin, 1903) by the same
method by which bisthiomorphide is made. The bisthiocodide is
soluble in alkalies and melts at 200°.
On treating bromocodide with ethyl mercaptain and sodium in
alcoholic solution while passing a current of hydrogen through the
solution ethylthiocodide is formed. The yield is about 90 per cent.
Chloromethylmorphimethine could not be prepared by treating
the iodomethylate of chlorocodide with sodium hydroxide, only
amorphous chlorine free products being obtained in the reaction. It
was prepared by digesting a-methylmorphimethine with phosphorus
trichloride in chloroformic solution at ordinary temperature in a
dry atmosphere and pouring the product into ether. The hydro-
chloride formed in the reaction was purified by recrystallization from
alcohol and ether. It melts at 177—178°. The free chloromethyl-
morphimethine could not be obtained in crystalline form. It was
converted into the iodomethylate by methyl iodide using acetone
and ether as solvents. The iodomethylate melts at 163° (corr.).
The hydrochloride of the phosphorous acid ester of methylmor-
6()
phimethine, C19H22NO2.O.P(OH)2.HCl, obtained by treating a-methyl-
morphimethine with phosphorus trichloride without using any sol-
vent, has the same crystalline form and the same , melting point as
the hydrochloride of chloromethylmorphimethine, C19H22NO2Cl.HCl,
prepared from the same reagents in presence of chloroform as Sol-
vent. Even a mixture of the two compounds shows no change in
melting point.
The basic products obtained by heating chloromethylmorphi-
methine with acetic anhydride differ according to the conditions of
the reaction. At a temperature of 170° under pressure the chief
product is methyloxethylamine, but if the heating is done in an oil
bath for a shorter time dimethyloxethylamine is obtained. The bases
were identified as chloraurates. Another compound found among
the products of the last reaction is tetramethylethylenediamine.
If the chlorination of a-methylmorphimethine is carried out by
means of phosphorus pentachloride in chloroformic solution, methyl-
morphimethine dichloride, C19H23NO3Cl2, is obtained. When treated
with methyl iodide in acetone solution the dichlorine derivative is
converted into an iodomethylate, C19H23NO3Cl2.0H31, which separates
out upon addition of ether. When heated with acetic anhydride the
methylmorphimethine dichloride yields the same decomposition pro-
ducts as chloromethylmorphimethine. (Ber., 1906, 3130.)
Morphenol.
E. Wongerichten and O. Dittmer have succeeded in converting mor-
phenol into 3.4.5-trioxyphenanthrene by fusing the former with
potassium hydroxide, pouring the reaction product into water
acidulated with sulphuric acid and then passing a current of carbon
dioxide mto the liquid. The precipitated trioxyphenanthrene is
purified by suspending it in water and shaking with ether and
separated from unattacked morphenol by shaking the ethereal
solution with very dilute sodium carbonate in which the trioxy-
phenanthrene is easily soluble whereas the morphenol is almost
completely insoluble in sodium carbonate. In pure water the trioxy-
phenanthrene is considerably more soluble then morphenol. Con-
centrated sulphuric acid colors it yellowish-red without any fluores-
cence (difference from morphenol). Exposed to the air it gradually
assumes a dark gray color. On exposing an alkaline solution of the
61
trioxyphenanthrene to the air the solution soon assumes an intensely
yellowish-brown color.
The formation of the trioxyphenanthrene from morphenol can
be represented by following equation:
g N
HO º Ho: 2 h
| 4.
HO /N
o( + H2O = | .
|
/N /
N / N Vº HO{ Y
* , ,
Ny/ N/
Morphenol, 3.4.5-trioxyphenanthrene.


Like phenanthrene, the trioxyphenanthrene is easily converted
(after acetylization) into an Orthoquinone which has some similari-
ties with morphol quinone but is not identical with it. Hence none
of the OH group of the trioxyphenanthrene is in the position 9 or
10 as in that case the quinone obtained from the trioxyphenanthrene
would be identical with morpholduinone.

Ho/ \
|
|
HON /N
- NCO
Y
N CO
º
N /
NZ
Morpholduinone.
On heating the trioxyphenanthrene on the water bath for three
hours with methyl iodide in presence of sodium methylate in a
closed tube, evaporating the product and taking up the residue with
ether a trimethoxyphenanthrene was obtained in the form of an oily
liquid. It was purified by converting into a picrate by means of an
62
alcoholic solution of pieric acid and then decomposing the picrate
with ammonia.
The oxidation products of the trioxyphenanthrene and its tri-
acetyl derivative could not be obtained in crystalline form.
(Ber. 1906, 1718.)
Mydriatic Alkaloid.
Ernst Schmidt and A. Kircher find that the seeds of that variety
of Datura fastuosa which is designated flor. coernl. plen, contain
0.22 per cent. scopolamine and 0.034 per cent. hyoscyamine whilst
those of the variety designated flor. alb. plen. contain 0.20 per cent.
Scopolamine and 0.023 per cent. hyoscyamine. A small amount of
atropine is present in both varieties. Datura fastuosa is, therefore,
not identical with Datura alba (comp. Shimoyama and Koshima,
Apoth. Zeit., 1892, 458).
Datura arborea obtained in the market was found to contain
scopolamine and hyoscyamine in the proportion 1:4. Another sample
of the plant grown in Marburg, several years old and gathered
when in flower, contained mainly scopolamine. A sample of a younger
plant gathered after it had flowered contained chiefly hyoscyamine.
The root of this plant contained only a little hyoscyamine.
(Arch. Pharm., 1906, 66.)
Oxycodeine.
L. Knorr and W. Schneider have investigated the compounds
obtained in the exhaustive methylation of oxycodeine which, to-
together with codeinone, had been previously obtained by Ach and
Knorr by oxidation of codeine (Ber. 36, 3067). As has been shown
by Knorr (Ber. 36, 3074) codeinone resembles thebaine in the be-
havior towards reagents, both giving thebenine when treated with
dilute hydrochloric acids and morphothebaine when treated with
fuming hydrochloric acid. Boiling acetic anhydride converts both
into ethanolmethylamine and 3-methoxy-4.6-dioxyphenanthrene. Oxy-
codeine on the other hand behaves towards reagents like codeine.
With acetic anhydride oxycodeine gives a diacetyl compound which
is hardly affected by boiling acetic anhydride at 180° and the products
obtained in the exhaustive methylation of Oxycodeine are analogous
to those obtained in the same reaction from codeine, the latter being
converted into a-methylmorphimethine which is decomposed by
acetic anhydride, while oxycodeine is converted into oxymethyl-
63
morphimethene which is also decomposed by acetic anhydride into
ethanoldimethylamine and methyldiacetyltrioxyphenanthrene, C14Hz-
•(O.CH3)(O.CH3.0O)2. This compound being derived from oxycodeine
must be different from the 3 methoxy-4.6-diacetyldioxyphenanthrene
obtained by the action of acetic anhydride upon codeinone. In the
same way the trioxyphenanthrene underlying the methyldiacetyl-
trioxyphenanthrene derived from oxycodeine, containing the new OH
group which enters the molecule in the oxidation of codeine to oxy-
codeine, cannot be identical with the trioxyphenanthrene which
underlies the 3-methoxy-4,6-diacetyldioxyphenanthrene obtained from
codeinone and which must contain the alcoholic OH group of codeine
but no new OH group. As the yield of oxycodeine is very small no
thorough investigation of the trioxyphenanthrene derived from it
could be made, but from the facility with which the new OH group
enters the reduced part of the codeine molecule the conclusion is
drawn that this OH is attached to a tertiary carbon atom of the re-
duced phenanthrene, i.e., to the same carbon atom to which is attached
the nitrogen containing side ring of the “morphium” alkaloids.
The oxycodeine used in this investigation was analyzed as a
picrate and a picrolonate. The picrate separates out in an oily
condition from a hot saturated aqueous solution, but on slow cooling
it crystallizes in prisms. The picrolonate is formed on mixing the
components in alcoholic solution and separates out as an oily liquid
which soon becomes crystalline.
Oxycodeine iodomethylate had been previously prepared by Ach
and Knorr using ethyl alcohol as a solvent and found to contain
half a molecule of alcohol of crystallization. The authors prepared
it by boiling oxycodeine with methyl iodide using methyl alcohol as
solvent and found it to contain one molecule of methyl alcohol of
crystallization.
Oxymethylmorphimethine, C19H23NO4, was prepared by boiling
oxycodeine iodomethylate with strong sodium hydroxide and extract-
ing the aqueous liquid with ether. Upon slow evaporation of the
ether the oxymethylmorphimethine separates out in crystals which
contain ether of crystallization and melt between 50–60° losing the
ether and becoming syrupy. On exposure to air the crystals lose
their ether of crystallization and become sticky.
Oxymethylmorphimethine dissolves in concentrated sulphuric acid
with a yellow color which disappears upon dilution with water. In
G4
this it differs from oxycodeine and the four isomeric methylmorphi-
methines which all give with cold sulphuric acid characteristic color
reactions. When the yellow solution of oxymethylmorphimethine ire
sulphuric acid is gradually warmed it assumes a raspberry red color
till the temperature rises to 60° when the red color again disappears.
A hydrochloride, a picrate and a picrolonate of oxymethyl-
morphimethine were prepared and analyzed.
When oxymethylmorphimethine is heated to 100° with alcoholic
potassium hydroxide (10%) a compound is formed which melts at
130° and forms an iodomethylate of a very high melting point
(about 300°). The compound differs from oxymethylmorphimethine
in that it dissolves in sulphuric acid with a violet-red color which
upon addition of water passes through blue-violet into green. These
properties of the compound would seem to indicate that it is not
an isomeric oxymethylmorphimethine as was supposed at first but
is identical with 8-methylmorphimethine.
On warming oxymethylmorphimethine on the water bath with
acetic anhydride, decomposing the excess of the anhydride by pouring
the solution in hot water, adding an excess of sodium carbonate
and shaking out with ether, diacetyloxymethylmorphimethine was
obtained in crystalline form. The diacetyl compound behaves to-
wards sulphuric acid exactly like oxymethylmorphimethine. It forms
an iodomethylate melting at 260° when treated with methyl iodide
in methyl alcoholic solution.
On treating oxymethylmorphimethine with methyl iodide an
iodomethylate was obtained which crystallized from water with 1%
molecules of water of crystallization which is not removed in desic-
Cat OI".
On boiling oxymethylmorphimethine with acetic anhydride it is
decomposed into a basic substance, ethanoldimethylamine, H.O.CH2.-
CH2.N(CH3)2, and a nitrogen-free compound, methyldiacetyltrioxy-
phenanthrene. The ethanol dimethylamine was isolated in the form of
its characteristic chloraurate. The methyldiacetyltrioxyphenanthrene
was purified by washing its ethereal solution successively with dilute
sodium hydroxide and dilute sulphuric acid and then recrystallizing
repeatedly from alcohol. It melts at 201° (the isomeric 3-methyl-
4,6-diacetyltrioxyphenanthrene obtained from codeinone melts at
162–163°). (Ber. 1906, 1414.)
65
L. Knorr continues his investigations of the morphium alkaloids.
In a previous paper (see preceding paragraph) it was shown that
Oxymethylmorphimethine obtained from oxycodeine can be decom-
posed by acetic anhydride into ethanoldimethylamine and methyl-
diacetyltrioxyphenanthrene. This phenanthrene derivative must have
the same relation to methylacetylmorphol obtained from codeine as
oxycodeine to codeine, i. e., the methyldiacetyltrioxyphenanthrene
obtained from Oxycodeine still contains the OH group (in the form
of an acetoxyl group) which is introduced into codeine upon oxida-
tion with chromic anhydride.
When this methyldiacetyltrioxyphenanthrene is oxidized methyl-
acetylmorphol quinone of known constitution is obtained. The
tertiary alsoholic OH group introduced into codeine when it is con-
verted into oxycodeine is therefore destroyed in the oxidation of the
methyldiacetyltrioxyphenanthrene to the quinone. Hence this OH
group must be in position 9 or 10 of the phenanthrene nucleus and
the two carbon

/N /N
cho. 2 N cº Y
$ 1|
|4 | |
CH3CO.ON /* CH3CO.ON /N
N/ N Y N-0
10 CrO3 |
| 9| | O.CH3C() X | |=
/N / /N /
| \ * Nº.
º sl º J
J/ N/
Methyldiacetyltrioxy- Methylacetylmorphol-
phenanthrene from oxycodeine. quin One.
atoms which form the “bridge” in the phenanthrene molecule must
be present in the form of CH groups in codeine and in methylmor-
phimethine. It follows from this that neither Freund's formulae for
thebaine and codeine (Ber. 1905, 323 £; 1906, 844) nor Pschorr's
formula of morphine (Ber. 1902, 4382) are correct. (In Freund's
formula for codeine the “bridge” is unsaturated, in Pschorr's formula
the “bridge” in codeine is dihydrated but in methylmorphimethine
it is unsaturated.)
66


N / CH3 º
y^/ |
o( |ch / º NH.
Y Yán * J B
%. N/ NN.CHs
2. h H |
Hohés CH HO. HCN /CH2
N/
CH2 Ho CH2
Codeine Codeine
(Freund's formula). (Pschorr's formula).
º
/~/N
03 |
N /N /
|H H
ºſº

Methylmorphinnethine
(Pschorr's formula).
If Freund's formula for codeine were correct both oxycodeine and
oxymethylmorphimethine ought to have phenolic character. Accord-
ing to Pschorr’s formula at least oxymethylmorphimethine ought
to have phenolic character. As neither of these compounds behave
like phenols these formulas cannot be correct.
The oxidation of methyldiacetyltrioxyphenanthrene was carried
out by means of chromic acid in glacial acetic acid solution accord-
ing to Wongerichten's method (Ber. 1898, 52). A comparison of the
resulting methylacetylmorpholduinone with the methylacetylmor-
pholduinone obtained from methylacetylmorphol showed that both
were identical. (Ber. 1906, 3252.)
67
Piperidine.
On comparing the oxidation velocities of diethylamine and piperi-
dine Th. Wallis found that the latter is so much more easily oxidiz-
able than the former that the difference could not be explained by
the cyclic structure of piperidine. It must be assumed that even the
best grade of commercial piperidine contains some partially reduced
pyridines which are much more easily oxidizable by potassium per-
manganate than piperidine and that these impurities act like oxygen
carriers causing the rapid oxidation of the hexahydro base. If
piperidine be purified by converting it into nitroso-piperidine the
impurities can be removed by subjecting the nitroso compound to
the action of potassium permanganate in acetone solution. Under
these conditions the impurities are easily oxidized and separate out
together with the manganese dioxide in form of potassium salts
whereas the piperidine, remaining unattacked, can be recovered by
decomposing the nitrosamine with hydrochloric acid and distilling
the piperidine hydrochloride thus obtained with potassium hydroxide.
Purified by this method piperidine has the same physical properties
as ordinary piperidine but differs from the latter in being unaffected
by potassium permanganate in alkaline solution. d
The presence of partially reduced pyridines in ordinary piperidine
is also shown by the fact that the acetyl derivative of ordinary
piperidine quickly absorbs bromine in aqueous or chloroformic solu-
tion whereas the acetyl derivative of piperidine previously purified
by the method described above hardly reacts with bromine even in
the course of an hour.
Attempts to purify piperidine by treating it with sodium and
boiling alcohol so as to convert the partially reduced pyridines into
piperidine were not successful. The product had the same oxidation
velocity as the original piperidine.
Another attempt to purify piperidine was made by treating it
with benzol sulphochloride in alkaline solution, subjecting the benzol
sulpho compound to fractional crystallization and then decomposing
the separate fractions by means of strong hydrochloric acid under
pressure at 150°. It was found that while the piperidine obtained
from the first fraction had a much lower oxidation velocity than
the original piperidine it was nevertheless not as pure as when
purified by the first method described above.
The nitrosopiperidine was made by treating a strong solution of
68
piperidine in presence of excess of sulphuric acid with a saturated
solution of sodium nitrite and extracting the nitroso compound
(most of which separates out as an oily liquid) with ether. The
ethereal solution was dried with potassium carbonate, the ether
distilled off and the nitrosamine distilled in vacuum.
The oxidation of the impurities in this nitrosopiperidine was
carried out by adding potassium permanganate to a solution of the
nitroso compound in acetone till the color did not disappear after
six hours’ standing. In the cold the reaction requires about two
days, in the heat the reaction is finished in about three hours. After
filtering off the manganese dioxide the unchanged nitroso piperidine
was obtained from the filtrate by evaporating the acetone, taking
up the residu with ether, and, after removal of the ether, distilling
the nitrosamine in vacuum.
The amount of potassium permanganate consumed in this reac-
tion is much greater when the liquids are allowed to get hot during
the reaction than when they are kept down by cooling to ordinary
temperature. As the properties and even the yield of pure piperidine
are the same in both cases the difference in the amounts of potassium
permanganate consumed, must be explained by assuming that at a
higher temperature either the impurities undergo a further oxidation
or the acetone itself is oxidized. wº-
The elimination of the NO group from the nitroso piperidine
could not be conveniently effected by means of sulphur dioxide in
hydrochloric acid solution. It was carried out by passing hydro-
chloric acid gas into a solution of a nitroso compound in toluol till
the evolution of nitrosyl chloride ceased and piperidine hydrochloride
separated Out.
The pure piperidine was obtained from the piperidine hydro-
chloride by distilling the salt with excess of potassium hydroxide.
(Ann. 345, 277.)
Purine.
O. Isay has devised the following synthesis of purine. 5. nitrouracyl
(I) is converted by means of phosphorous oxychloride into 2.4-di-
chlor-5-nitropyrimidine (II), the latter when treated with ammonia
in the cold is transformed into 4-amino-2-chlor-5-nitropyrimidine (III)
which upon reduction with hydriodic acid and phosphonium iodide
gives 4.5-diaminopyrimidine (IV) and the diamino compound when
condensed with formic acid yields purine (W).
69
NH–-CH N==CH N===CH
| | PO.Cls i NH3 || | HI
CO C.NO2 ——x C.Cl C.NO2 ——x C.C. C.NO2 —X
| | | | | PH4I
NH–CO N—C.Cl N—C.NH2
(I) (II) (III)
N=-CH 1N==60H
| | H.CO2H | |
———) CH C.NH2 ———X 20 H sº NHS
| | | | 280h
N—C.N H2 an—at . N^
(IV) (V)
Purine.
The yield of purine by this method is very small for the reason
that the preparation of the 5-nitrouracyl and its conversion into
2.4-dichlor-5-nitropyrimidine are connected with considerable loss of
material.
The 5-nitrouracyl was prepard from methyluracyl by the method
of Behrend and Lehmann (Ann. 240, 4; 251, 238). It was separated
from the 5-nitrouracyl-4-carboxylic acid formed in the reaction by
recrystallizing the compound from hot water.
The 2.4-dichlor-5-nitropyrimidine was prepared by heating 5-nitro-
uracyl with a large excess of phosphorus oxychloride to about 185°
in sealed tubes under constant shaking. The length of time required
to carry the reaction to a finish depends upon the amount of hydro-
chloric acid present in the phosphorus oxychloride. It is, therefore,
best to redistill the oxychloride so as to remove all the acid and
then add a couple of drops of the latter. The reaction product is
distilled in vacuum at 55° and the unchanged oxychloride removed
by means of ice water. The pyrimidine compound is then shaken
out with ether and, after removal of the ether, purified by distillation
in vacuum. It forms shining leaflets melting at 29.3° and boiling
at 153–155° at a pressure of 58 mm. Its vapors have a penetrat-
ing odor and attack the eyes.
On treating the 2.4-dichlor-5-nitropyrimidine (II) with cold
alcoholic ammonia the 4-amino-2-chlor-5-nitropyrimidine separates
out immediately as a white precipitate and can be recrystallized
from hot water. By using standardized ammonia it could be shown
that the reaction takes place according to the following equation:
C4N2H(NO2)Cl2 + 2NH3 = NH4Cl + C4N2H (NO2)Cl(NH2).
70
As in most pyrimidine derivatives the chlorine atom in 4 is more
easily replaceable by the NH2 group than the chlorine atom in the
mesoposition the compound obtained in the last reaction must con-
tain the NH2 group in 4, not in 2. This was also shown by the
fact that after converting the NO2 by reduction into the NH2 group
the resulting compound gave all the reactions of orthodiamines.
The 4-amino-2-chlor-5-nitropyrimidine is soluble in strong hydro-
chloric or sulphuric acids and separates out unchanged upon dilution
with water. It is also soluble in alkalies but cannot be recovered
from such solution. It is not affected by boiling silver nitrate and
has a neutral reaction. It affects the eyes and the mucous membrane
of the nose and throat and causes burns on sensitive skin.
Sulphur dioxide had no effect upon 4-amino-2-chlor-5-nitropyri-
midine but hydriodic acid and plmosphonium iodide reduced it to
4.5-diamino pyrimidine (IV) which melts at 202.5° and boils at 229°
under a pressure of 32 mm. It is very easily soluble in water and
alcohol but insoluble in ether. It forms a hydrochloride, a hydro-
bromide, a chloroplatinate, a chloraurate and a picrate.
When the 4.5-diaminopyrimidine is boiled with anhydrous formic
acid and, after removal of excess of acid, the liquid made alkaline
with ammonia formyl-4,5-diaminopyrimidine separates out in pris-
matic crystals.
N==CH
|
CH C. N II. HCO
| |
N—C.N II 2
Formyl-4 5–diaminopyrimidine.
As experiments had shown that only such pyrimidine derivatives
had an alkaline reaction as contained a n N H2 group in 4 or 6
and the formyl compound had an alkaline reaction in aqueous solu-
tion the compound must contain the formyl group in 5.
On heating the formyl compound first in an at mosphere of car-
bon dioxide and then in vacuum it is transformed into purine (W)
which distills over as an oily liquid and which soon solidifies to a
mass of needle-shaped crystals. The identity of this purin with the
compound obtained by E. Fischer was established by a comparison
of the melting points of the substance itself as well as of its picrate
and nitrate. Other reactions of purine described by Fischer were
also given by the synthetic compound of the author.
71
The 4.5-diaminopyrimidine (IV) was also condensed with other
substances as follows: o
1. On heating the diamino compound with acetic anhydride in
an atmosphere of carbon dioxide to 210° and then distilling the
residue in vacuum 8-methylpurine distills over as a yellowish oil
which solidifies to needle-shaped crystals.
N==CH
| |
CH ºcc
|| || SC.CH
N_{, , N/*
8-Methylpurine.
(VI)
The compound is soluble in water with a neutral reaction and melts
at 265–266°. It gives all the reactions of the purine compounds.
2. On heating the 4.5 diaminopyrimidin with urea to 16.5°
ammonia is given off and 8-oxypurine is formed which melts at 312°
and is identical with the compound obtained by Fischer by reducing
8-oxy-2,6-dichlorpurine
N==CH
l t
CH. C.NH
|| || CO
N—C.NH
8–Oxypurine.
(VII)
3. On heating the 4.5-dianimopyrimidine with thiourea to 220°
in an atmosphere of carbon dioxide it is converted into 8-mercapto-
pyrine, which is soluble in ammonia and fixed alkalies, and when
heated emits an odor of caoutchouc
N==CH
| |
CH (J. NH
|| || Xcs
N—C.NH
8–Mercaptopurine.
(VIII)
4. On heating 4.5-diamidopyrimidine with benzil to 175° an
azine of following constitution is formed
N==CH
| |
CH C.N==C.06H5
| | |
N—C.N==C.06H5
Azine.
(IX)
72
The azine is insoluble in water or alkalies, easily soluble in alco-
hol, benzol and toluol. It melts at 170.5° and becomes electric
when rubbed up.
On heating the 2,4-dichlor-5-liitropyrimidine (II) with alcoholic
ammonia in closed vessels to about 100° both chlorine atoms are
replaced by NH2 groups with the formation of 2,4-diamino-5-nitro-
pyrimidine
N=0H
(NH. *No.
| |
N C.NH2
2.4.-diamiño–5-nitropyrimidine.
(X)
'The diamino compound does not melt even at 260° and sublimes
at a high temperature with partial decomposition. It is difficultly
soluble in water and and forms salts with acids.
By reducing this diamino compound with stannous chloride it is
converted into 2.4.5-triaminopyrimidine
N=0
| |
(). NH 2 C.N H2
| |
N C. NH2
2.4.5-triaminopyrimidine.
(XI)
The triamino compound melts at 176–179° and is isomeric with
the triamino compound previously obtained from barbituric acid by
Gabriel (Ber. 34, 3364) which melts at 245–246°. It has a strong
alkaline reaction, reduces Fehling's solution and precipitates metallic
gold from gold chloride. It is very difficultly soluble in ether, chloro-
form or petroleum ether, but easily soluble in acetone or alcohol
with a red color. It forms difficultly soluble salts with acids and
gives the murexide reaction. Exposed to the air it becomes red.
On boiling the tria mino compound with crystallized formic acid
for half an hour it is converted into formyltriaminopyrimidine
N-ºn
|
C.NH 2 (). NH HCO
| |
N C.NH2
* Formylt, iaminopyrimidine.
73
As the formyl compound has an alkaline reaction and is capable
of forming a closed ring the formyl group must be in 5, not in 2 or
4 (see above formyl-4.5-diaminopyrimidine). The formyl compound
melts at 224°, becomes solid at a higher temperature and then does
not melt at 260°. It is difficultly soluble in water or alcohol and
, forms salts with acids.
On heating the formyl compound to 300° it is converted into
2-aminopurine or isoadenine
N CH
... .
G.N.H. G.NHS
| |
N 6. N*
U. C. amino purine (isoadenine).
(XII)
CH
The isoadenine differs from adenine (6-aminopurine) in not giving
a purple color with zinc and hydrochloric acid (Kossel and Fischer's
reaction) and is identical with the isoadenine previously obtained
by Tafel and Ach (Ber. 34, 1177). (Ber. 1906, 250.)
Caffeine.
As is well known xanthine and its methyl derivatives, heteroxan
thine, paraxanthine, theophylline and theobromine, can be converted
into caffeine (trimethylxanthine). E. Fischer and F. Ach show that
vice versa by successively splitting off methyl groups from caffeine
the alkaloid can be converted either into xanthine itself or any of
its methyl derivatives.
When 8-chlorcaffeine (I) is heated with phosphorus pentachloride
CH3.1N—600 CH
| | . 3
20O &NO
i | 280.0
CHs.sv-46.9N’
8-Chlorcaffeine.
(I)
using phosphorus Oxychloride as a solvent or when chlorine is
passed into melted caffeine 3’.8-dichlorcaffeine is formed
cº-ſo CH3
go C.N C
| .Cl
CH2C.N–6.N/.
3’.8–Dichlor caffeine Or
3-chlormethyl-8-chlorparaxanthine.
(II)
74
which is purified by pouring off from the unattacked 8-chlorcaffeine,
evaporating to dryness, dissolving residue in chloroform and, after
washing the solution with water to remove traces of the phosphorus
chlorides, eyaporating the solvent to a thin syrup. On mixing this
syrup with dry ether and evaporating the solvent the dichlor com-
pound separates out in crystals and can be washed free from adhering
syrup by means of benzene. The compound is very difficultly soluble
in cold water but easily soluble in chloroform, benzol, acetone and
acetic ether and gives the murexide reaction. In the mother liquor
of the dichlor compound there seems to be a small amount of a
trichlor compound.
When the 3’.8-dichlorcaffeine is boiled with water formic aldehyde
and hydrochloric acid are given off and on cooling 8-chlorparaxan-
thine separates out in crystals.
CH3.N.—CO CH3 Q.
CO C.N
| || >C.Cl
NH-6.N/
8-Chlorparaxanthine.
(III)
It can be recrystallized from hot water and dried at 100°. By
reduction it can be converted into paraxanthine.
If the 3’.8-dichlorcaffeine be boiled with methyl alcohol instead
of with water 37.8-methoxy-chlorcaffeine is formed
CH3.N.—CO CH3
| |
CO &NO
| || >C.Cl
CHs.O.CH2N–6.N/
37. Methoxy-8-chlorcaffeine.
(IV)
When heated with hydrochloric acid (1.19) to 100° the methoxyl
group is eliminated and 8-chlorparaxanthine (III) is formed.
On passing chlorine into a solution of caffeine in nitrobenzene or
phosphorus oxychloride at 90–100°, evaporating the solvent under
reduced pressure and recrystallizing the product from methyl alcohol
the alkaloid is transformed into 7.8-dichlorcaffeine t
CHA.N-GO CH, C,
to C.N&
| || }00
CHs.N–ČN/
7’.8-Dichlorcaffeine. '
(V)
75
The 7.8-dichlorcaffeine differs from the 3’.8-dichlorcaffeine (II) in
that the former is not affected by boiling methyl alcohol. Boiling
with water converts the 7.8-dichlor-compound into 8-chlortheophyl-
line with the elimination of hydrochloric acid and formic aldehyde
CH3.N to
|
CO C. NH
Nr.
ch, k & Nº"
8-Chlortheophylline,
(VI)
By reduction the 8-chlortheophylline can be converted into theo-
phylline.
On heating the 7.8-dichlorcaffeine with sodium ethylate, filtering
off from the sodium chloride and cooling the liquid diethoxycaffeine
separates out in needle-shaped crystals.
*. CH3.N-00 CH, O.C.H.
|
o CNA
ſº
CHs.N—ć.N’
7’.-Diethoxycaffeine.
(VII)
C.O.C2H5
The compound is insoluble in hot dilute sodium hydroxide but soluble
in hot dilute hydrochloric acid, benzol and glacial acetic acid.
On heating 7.8-dichlorcaffeine with a solution of chlorine in
phosphorus oxychloride to about 160° under pressure, concentrating
the liquid at 45° under a pressure of 15–20 mm. and dissolving the
residue in hot benzol tetrachlorcaffeine was obtained which separated
out in yellowish crystals upon concentration of the benzol solution.
It was purified by shaking its solution in warm ether with animal
charcoal, concentrating the ethereal solution and then cooling with ice.
CI.CH2.N go CH2. Ol
Go C.N&
cichº dº"
17.3’.7/.S-Tetrachlorcaffeine.
(VIII)
The tetrachlorcaffeine is easily soluble in acetone, benzol, glacial
acetic acid and alcohol. It is also soluble in hot water but the
aqueous solution is soon decomposed with elimination of formic
aldehyde. It is insoluble in dilute alkali.
By warming the tetrachlorcaffeine with sodium methylate dis-
76
solved in absolute methyl alcohol, neutralizing the liquid with acetic
acid and evaporating to dryness tetranethoxycaffeine was obtained
as a crystalline mass which was recrystallized from hot water. It
was purified by repeated recrystallisation from methyl alcohol and
ether. It is easily soluble in glacial acetic acid, hot alcohol, benzol
and chloroform.
CH3.O.CH2.N.—CO CH2.O.CH3
go ºn 2000H.
CH3.O.CH2.N.—C.N
Tetramethoxycaffeine,
(IX)
On boiling a solution of tetrachlorcaffeine (VIII) in a mixture of
two volumes of glacial acetic acid and one volume of water for ten
hours formic aldehyde and hydrochloric acid are eliminated and
8-chlorxanthine crystallizes out upon concentrating the liquid. In
order to complete the reaction it was necessary to add more glacial
acetic acid and continue the boiling for another hour while passing
a strong current of steam.
NH-60
ČO (3.NH
| | XC.C.
NH-C. Nº
8-Chlorºxanthine,
The chlorxanthine was purified by converting it into the am-
monium Salt which crystallizes well, then recrystallizing the ammoni-
um Salt from very dilute ammonia and decomposing the salt in
aqueous solution by acetic acid.
On boiling the chlorxanthine with strong hydriodic acid (1.96)
and phosphonium iodide the hydriodide of xanthine was prepared
from which free xanthine was liberated by ammonia.
(Ber., 1906, p. 432.)
Quinine.
According to H. Lacroix neutral quinine formate commences to
lose formic acid at 50° and the loss is complete at 95° the residue
being pure quinine soluble in ether chloroform etc. Dissolved in
Water the neutral salt dissociates into formic acid and basic quinine
formate giving a solution of a decidedly acid reaction.
The basic quinine formate (quinoform) is not dissociated even
by boiling water and melts at 109° (not at 132° as previously re-
77
ported) with decomposition. The specific rotation of the basic salt
obtained from a one per cent solution at 20° is [a]p20 = –144.2°
(not –141.1° as previously reported.) (J. pharm. chim., 1906, p. 493.)
E. Comanducci and L. Pescitelli have prepared the sulphur ethers
of quinine and cinchonine by heating the alkaloids in chloroformic
solution with phosphorus pentasulphide. After filtering off from the
excess of the latter and removal of the chloroform by distillation
the product was recrystallized from alcohol.
Thioquinine, (C20H23N2O)2S, forms a yellowish microcrystalline
powder coagulating at 140–142° and melting at 150–152°. It
has an odor of onions and is soluble in alcohol or chloroform but
insoluble in ether. It gives fluorescent solutions when dissolved in
dilute sulphuric or nitric acid, and the solutions retain the same .
odor. Alkalies reprecipitate the base from these solutions. It gives
the thalleioquin reaction and when threated with chlorine, ammonia
and potassium ferrocyanide assumes a red color. It also gives the
herapathite reaction.
Thiocinchonine, (C19H21N2)2S, was prepared by the same method
as thioquinine. It forms an amorphous powder of a decided
alliaceous odor, decomposes without melting when heated to about
190–192°, is soluble in alcohol or chloroform but insoluble in ether
Or Water. (Gazz. chim. ital., 1906, p. 781).
TWO formates of quinine were prepared by P. Guigues, a neutral
formate and a basic formate. The neutral salt, C20H24N2O2(CH2O2)2,
was made by dissolving quinine in excess of dilute formic acid and,
after neutralizing with dilute ammonia, concentrating the liquid on
a water bath. The salt melts below 100° and loses some formic
acid when kept in the neighborhood of that temperature. It is
easily soluble in water and the solution is neutral to phenolphthalein
but is both acid and alkaline to litmus. The basic formate,
C20H24N2O2.0H2O2, was made by dissolving quinine in the theoretical
amount of formic acid and adding a strong neutral solution of
ammonium formate. The basic salt is stable in the air, is not
altered when heated to 100° and dissolves in less than 20 parts of
Water. (J. pharm. chim., 1906, p. 301.)
Solanine.
M. Wintgen has assayed a large number of various samples of
potatoes for Solanine. The method consisted in extracting the
78
potatoes with alcohol, evaporating the solvent, dissolving the residue
in acidulated water and precipitating the solanine with ammonia.
Both healthy and sick potatoes were examined. Experiments were
also made in order to establish whether solanine is developed by
prologed keeping or by certain bacteria as is claimed by Weil and
Schnell (Arch. f. Hygiene, 1900, 33, p. 330; Apoth. Ztg., 1898, 13,
p. 775, and 1900, 15, p. 133). The results obtained were as follows:
The amount of solanine in different samples varies between very
wide limits but is much smaller than is generally given in literature.
(The highest amount obtained was a little more than 100 milli-
grams of solanine per kilogram of potatoes). Most of the solanine
is present in the outer parts of the tubers greatly diminishing to-
wards the center. An increase of Solanine by keeping does not take
place. Sick potatoes do not contain more solanine than healthy
ones, Solanine is not formed by bacteria.
From these results the author draws the conclusion that cases
of poisoning by potatoes must be due to some other causes, not to
the small amount of solanine contained in them.
(Arch. Pharm., 1906, p. 360.)
G. Oddo and A. Colombano find that the only criterion of purity
for Solanine obtained from Solanum Sodomaeum is the uniform pris-
matic shape of crystals which can be observed under the microscope.
The purification of the alkaloid is effected by first recrystallizing it
from 80% alcohol, then dissolving it in dilute sulphuric acid and
reprecipitating with pure sodium hydroxide. The alkaloid is then
again repeatedly recrystallized from 80% alcohol till uniform prisms
are obtained. It has no definite melting point undergoing gradual
decomposition when heated. Owing to the very low percentage of
nitrogen it contains its formula cannot be established with certainty
by analysis. While according to former analyses the formula was
given as, C23H39NO6, later results correspond better to C27H47NO9.
(Gazz, chim. ital., 1906, II, p. 522.)
Sparteine.
According to renewed experiments by M. Scholtz the results ob-
tained in a previous investigation of the author in collaboration
with P. Pawlicki (Arch. Pharm., 1904, 513) are not quite correct.
While sparteine is undoubtedly a diacid base it is nevertheless
very difficult to combine it with two molecules of alkyl halides.
79
When heated with ethyl iodide in alcoholic solution the alkaloid is
converted not into the diiodoethylate, C15H26N2(C5H2I)2, but into
the hydriodide of the monoiodoethylate, C15H26N2.02H5I.HI (Mills,
Ann., 1863, p. 71). The tendency of sparteine to split off hydriodic
acid from alkyl iodides is so strong that when treated with some
alkyl iodides nothing but the hydriodide of sparteine is formed.
Thus, while at ordinary temperature sparteine slowly combines with
ethyl iodide to an addition product, the compound formed at 150°
consists of sparteine hydriodide alone. Whether the iodoethylate of
sparteine is treated with methyl iodide or the iodomethylate is
treated with ethyl iodide there is no reaction at ordinary tempera-
ture while at higher temperatures decomposition takes place and
sparteine hydriodide alone is produced. With some alkyl iodides
sparteine does not combine at all. Thus, when treated with amyl
iodide or the methyl ester of iodoacetic acid only sparteine hydriodide
is formed. With benzyl iodide Sparteine combines at ordinary tem-
perature to an addition product, C15H26N2.06 H5.C2H5I, but at the
same time a small amount of Sparteine hydriodide is also formed.
When the iodobenzylate is warmed with the methylester of iodoacetic
acid again only a hydriodide is produced.
While it is difficult to make both nitrogen. atoms of sparteine
combine with alkyl iodide there are nevertheless two compounds in
each of which both N atoms are linked to a halogen atom and to
four organic radicles. One is the previously described addition product
of sparteine and ortho-xylylene bromide, C15H26N.C6H4(CH2Br)2. In
this compound both N atoms are pentavalent as shown by the
following formula:
BI'
/
C15H2
1. º
B
C6H4
This composition of the compound was shown by an analysis of
the platinum compound obtained by converting the bromide into
the corresponding chloride by means of silver oxide and hydrochloric
acid and then precipitating with platinum chloride.
The other compound in which both N atoms are pentavalent is
the diiodomethylate obtained but not analyzed by Moureu and
80
Waleur (Compt. rend. 140, pp. 1601, 1645; 141, pp. 49, 117, 261).
The composition of this compound, too, was shown by an analysis
of the platinum salt.
The existence of two isomeric monoiodomethylates and two
isomeric monoiodoethylates of sparteine is explained by Moureu and
Waleur by assuming the isomerism to be of a stereochemical nature.
They show that the hydriodide of either of the isomeric monoiodo-
alkylates when heated to 232° loses alkyl iodide and yields one and
the same sparteine hydriodide, hence in both isomerides the alkyl
iodide must be linked to one and the same N atom and the isomerism
must be due to stereochemical difference. That the formation of one
and the same hydriodide cannot be accounted for by assuming that
at the high temperature of the reaction the hydriodic acid changes
its place is shown by these authors by the fact that when the
hydriodide of one of the isomeric monoiodomethylates is heated
with excess of methyl iodides to 135° only there is also formed a
Small amount of the hydriodide of the other monoiodomethylate.
As at this comparatively low temperature the hydriodic acid is not
apt to change place the hydriodide of the second monoiodomethylate
cannot be formed except by a stereochemical transformation. In
this the author of this paper does not agree with Moureu and Valeur.
He thinks that the isomerism is due to a difference in position of
the alkyl iodide with regard to the N atoms and that both at 232°
and 135° the hydriodic acid changes its place.
According to Moureu and Waleur sparteine has one or the other
of the following formulae
(; H CH CH CH
/N /N N N
H2C/ | NCH2 II 20/ | NCH2 II2C/ | NCH-CH2 — HC/ CH2
ºil. º CH2 CH2
Ol' |
H º I C º (H2 CH2 ºil.
20N CII—CH2— HCN yon. H2CN | ZCH2 tº you.
Ny/ N NZ N
N N N N -

and the supposed stereoisomerism is ascribed by them to the penta-
Valency of nitrogen in the iodoalkylates. But, as it was shown by
the author in the case of coniine and conby drine, only such derivatives
of these bases form isomeric iodoalkylates as contain an asymmetric
N atom, i. e., an N atom linked to five different radicles. This con-
81
dition not being fulfilled in either of the above formulae the isomerism
cannot be due to a stereochemical difference in the N atoms.
Comparative physiological tests of the sparteine alkyl halides
showed that while they exert a favorable influence upon the heart
they have an injurious effect upon the respiration.
º (Arch. Pharm., 1906, p. 72.)
Thalleioquin.
According to H. Fühner the thalleioquin reaction given by
quinine, cupreine and other derivatives of para-oxyquinoline depends
upon the formation of a dichlorketone compound. This is shown by
the fact that dichlorketoquinoline, obtained by the action of chlorine
upon the hydrochloride of paraoxyquinoline in aqueous solution,
gives the thalleioquin reaction when treated with ammonia, while
~. ('H' C.Cl2
…N (; />
º - HC., Ny CO
H "N/º, ('H
Diehlorketoquinoline.
other chlorine derivatives of para-oxyquinoline , do not give the
reaction with ammonia. The blue compound formed by the action
of ammonia on the dichlorketoquinoline the author names thalleio-
quinoline and the derivatives of this compound obtained from
quinine, cupreine, quinidine, etc., are named thallioquinine, thalleio-
cupreine, thalleioquinidine respectively.
A compound similar or possibly even identical with thalleio-
quinoline seems to be formed by treating 5,6-quinoline quinone with
ammonia
(!()
- A N
/* \ ^ NCO
N 2^ /
N. 2’ \ 2.
>< </
N
5, 6-Ouinolinequinone.
“The formula of thallioquinoline seems to be C1s H14N402. As
aminooxyquinoline assumes a green color when heated it is possible
82
that the compound is under these conditions 6xidized to thalleio-
quinoline. 2C9H8N2O + O = C1s H14N4O2 + H2O
- * - C.NH2
/ ` Nºon
| •l
|
N. /N /
NZ ~/
N
- - - - - Aminooxyquinoline. -
The conversion of dichlorketoquinoline into thalleioquinoline can
be effected only by ammonia, not by any other alkali. -
The formula of thalleioquinoline is either that of an indamine (I)
or that of an oxazone (II) - -
C–O.NH4 CO /
/ ^ /N N
Z Sy’ S. C—N= C/ / - N
| |
S. /~ CH H(X| / 3. § /
~/ N / `s / \ Ž
N (H U}H N
Diquinolyl-ind amine-ammonia.
(I)
- * …N. Af ...Aſ ‘. º
2^ ZN N N
ſº-º-º/N
| | | |
N. : A N /CH HCN /N /
N/ N/ N/~/
N CH (; H N
Diquinolyloxazone-ammonia.
(II)
In both formulas the nitrogen atom which links the two quino-
line molecules is assumed to be in the para-position to the nitrogen
atom of the quinoline counplex. This assumption is made owing to
the similarity between thalleioquinoline and the quinone amide dyes.
When thalleioquinone is warmed with sodium or barium hydrox-
ide there is an evolution of ammonia which shows that thalleio-
quinoline, like murexide, is an ammonium salt (see Ann. 1904, p. 333).
Owing to certain similarities in the behavior of thalleiquinoline
with that of the indamines the author considers the indamine formula
(I) as the more probable one. (Arch Pharm., 1906, p. 602.)

83
- - Thebaine. -
M. Freund has succeded in converting theoaine into codeine. On
treating thebaine with bromine in chloroformic solution a hydro-
bromide of a brominated base in crystalline form is found among
the products, of the reaction which corresponds to the formula
C1s H20 BrNO4.HBr. The free base underlying the hydrobromide has
the formula C1s H18 BrNO3, i. e., contains one molecule H20 less than
it does in the salt. In the same way on converting the base into
the hydrochloride the salt has the formula, C1s H20 BrNO4.HCl, while
the base liberated from the hydrochloride corresponds to C18H18-
BrNO3.
The new brominated base contains one methylimide and only
one methoxyl group showing that, as in the conversion of thelbaine
into thebenine or morphothebaine, in the transformation of thebaine
into the brominated base one of the methoxyl groups of thebaine is
eliminated.
That the brominated base is neither monobrom thebenine nor
monobrommorphothebaine is shown by the fact that it is insoluble
in alkalies while thebenine and morphothebaine containing a phenolic
OH group are both soluble in alkalies. The brominated base reacts
with hydroxylamine forming a crystalline oxime with elimination of
bromine. Most probably the reaction is as follows: -
1. C18H18 Brº ()3 + H2N.OH = C18H18 Brx O2 . N. () H + H2O
2. TC18H18 Brx O2 . N.OH + H2O = C1s H1s(OH)NO2 . N.OH + HB1.
That the brominated base is really a ketone is also shown by the
fact that nascent hydrogen converts it into codeinone identical with
the codeinone previously obtained by Ach and Knorr (Ber. 1903,
p. 3067). -
- ('1's H18 Bry(); + 2H = C18H19NO; + H Bl"
The brominated base is therefore monobromcodeinone and its
formation from thebaine can be explained by assuming that at first
the double binding of the ring containing the nitrogen bridge is
removed and two atoms of bromine are taken up forming thebaine
dibromide. The dibromide then loses one molecule methyl bromide
and changes to monobromcodeinone. The bromcodeinone when
treated with nascent hydrogen is converted into codeinone. As
according to Ach and Knorr codeinone can be reduced to codeine
the above reactions enable us to convert thebaine into codeine.

84
The reactions taking place in the conversion of thebaine into
codeine can be represented by the following scheme:
/N 4. /
(Ha.0/. N CH3.0/
| |
N Vº N … N,
2 Y N
( * -º-º-º-º- º ammºmºms imsº
) Jºh / |- % CH | X-
N /N ,’
/ N/ / >/.. .
C|So, |('H CN2, |CII .
3& %22
* *\ *]
CHA.O's ZCH CH3. (). I}r() /CH
6 N
CII ('H, I81.
Thel) uine Dil) rOnn thebaine
... a zºº /
º S. CIIa.()/
|
| | |
`s /. 2." N 2 N
* *. —l– ſ * — —
() |CH H ('II & IBI X- () |(}II
‘. . / | 2’ //
J/ |/| N/
("|N, , |(}|| ('N, ( II
(3/, º,
2.v. 24
O:( , / HO. HCN /CII
sº N
('H. Bl" (H. Bl'
Monobromcodeinone Codeine
The conversion of thebaine into codeine corroborates the pre-
viously (Ber. 1897, p. 1373) expressed opinion of the author that
thebaine, morphine and codeine all have the same constitution aud
that the difference in decomposition products obtainable from the -
baine on the one hand and morphine and codeine on the other is due
to the deggee of reduction of the phenanthrene complex underlying
the three alkaloids. The opinion is also supported by the observa-
tion of Knorr (Ber. 1903, p. 3074) that the enol form of codeinone
having the same type as thebaine really yields the same decomposi-
tion products as the latter.
85
The hydrobromide of bromcodeinone can be made by one of the
following methods. 1. A solution of bromine in chloroform is added
drop by drop to an ice cold solution of thelbaine in the same solvent
and the chloroform sucked off in a desiccator. On dissolving the
brown viscous residue in hot alcohol only a small amount of crystals
separate out on cooling. 2. Instead of removing the chloroform it
is shaken with dilute hydrobromic acid for about half an hour a hol
the crystals which separate out recrystallized from very dilute
alcohol. 3) A solution of bromine in glacial acetic acid is added
to a cold solution of thebaine in the same solvent and the crystals
which separate out on standing are recrystallized from very dilute
alcohol.
The hydrobromide has a yellowish-brown color and corresponds
to the formula, ('1's H1's Brn Oa. HBr + H2O. The water cannot be
removed by heating the salt to 130° in a current of hydrogen. The
free brominated base is precipitated from the hydrobromide by
ammonia, alkalies or alkaline carbonates. The monobromcodeinone
is insoluble in excess of alkali. On prolonged boiling with alkali it
goes into solution with partial decomposition. When heated for a
few minutes with hydrochloric or hydrobromic acid most of the
bromcodeinone crystallizes out unchanged.
The hydrochloride of bromcodeinone separates out in needles
when bromcodeinone is dissolved in hot, dilute hydrochloric acid.
Dried at 100° the salt has the formula, C1s His BrxO3.HCl + 2 H2O.
One molecule of water can be driven off at 150° leaving a compound
in which the second molecule of water must belong to the constitu-
tion of the salt.
The free bromcodeinone was obtained in crystalline form by
adding ammonia to a solution of bromcodeinone hydrobromide in
dilute alcohol. It is insoluble in water, difficultly soluble in ether
but easily soluble in chloroform. It does not react with methyl
iodide to form an addition eompound but when heated with methyl
iodide to 100° is converted into the hydriodide of bromcodeinone.
As, according to Ach and Knorr (Ber. 1903, 3073) codeinone easily
combines with methyl iodide, the stability of bromcodeinone towards
this reagent must be ascribed to the influence of the bromine atom
upon the nitrogen atom.
The oxime of oxycodeinone, C1s H1s(OH) (; N.OH), was obtained
by boiling the hydrobromide of bromcodeinone with hydroxylamine
86
hydrochloride till the hydrobromide did not separate out any more
on cooling the liquid. After setting the oxime free it was shaken
out with ether. The oxime is soluble in dilute alkali:
The conversion of bromcodeinone into codeinone was accomplished
by digesting the hydrobromide of bromcodeinone with iron filingss
in presence of dilute sulphuric acid in the cold until the salt went into
solution. The filtered liquid was then made alkaline with sodium
carbonate and shaken out with chloroform. The codeinone was
identified by the melting point of its oxime. (Ber. 1906, 844.)
L. Knorr and H. Hörlein have succeeded in converting theljäine
into codeinone and codeine. It had been shown by Ach and Knorr
(Ber. 1903, 3067) that potassium permanganate or chromic acid
oxidizes codeine to codeinone which by reduction can be reconverted
into codeine. This codeinone occupies an intermediate position
between codeine and thebaine. -
C1s H31NO3 C18H19NO; & ('19 H21NO3
CO (leine CO (lein One Thebaine
According to Knorr (Ber. 1903, 3074) thebaine is the methyl ether
of the enol form of codeinone and the relation between morphine,
codeine, codeinone and theoaine can be expressed by the following
scheme in which the arrows indicate the transformations so far
accomplished :
- —() H —O.CII3 —O.CH3
C15H11N () > —CH.OH —) (15 H 14NO - —CH. ().H. a-2 C15H14NO > –0 = ()
| | |
—CH2 —CH2 —CH2
Morphine CO (leine Codeinone
—O.CH3 -
C15H14NO > —C.O.CH3. ... (in 6)
|
—CH
Thebaine
The methoxyl group of thebaine situated in (6) of the
phenantlarene nucleus is so easily saponified that in the transforma-
tion products in the preparation of which acids are used the CH3()
group is replaced by an OH group. In the transformation of the-
baine into thebenine, for example, the saponification of the CH3C)
group is effected even by dilute acids in the cold upon standing or
by a few minutes' boiling with dilute hydrochioric acid. As phenol
87
ethers are generally not easily saponifiable the easy saponification
of the CH3O in (6) of thebaine must be ascribed to the presence of
the double binding next to the carbon atom to which the (‘Hä0
group is attached. All such derivatives of vinyl alcohol are easily
changed into an alcohol and an aldehyde or a ketone
(R1||R2 = (XR3 (). Alkyl + H2() = (XIII: 1 IR2 — (XR3 = () -- Alkyl.() II
(As all such derivatives of vinyl alcohol can be looked upon as
ethers of the enol form of aldehydes or ketones the authors pro-
pose to call such ethers enol ethers). In the conversion of thebaine
into thebenine or morphothebaine the the Baine is most probably
first converted into the ketone codeinone according to above equa-
tion. While this supposition is supported by the fact that codeinone,
like thebaine itself, can be converted into thebenine, morphothebaine
or thebainone (Ber. 1905, 3160 and 31.70) it is only now that the
authors have succeeded in directly converting thebaine into codeinone.
Attempts to reconvert codeinone into thebaine by passing through
the Ortho ether of codeinone
—().('H3
—(). ('H:3
—(). ('H&
—('
('15 II 1 INO
|
—('H2
which ought to be obtained by the action of ortho formie ester on
codeinone were not successful.
The conversion of thebaine into codeinone was carried out by two
methods:
1. Boiling with normal sulphuric acid. On boiling thebaine with
normal sulphuric acid for 6–7 minutes, and shaking out the cooled
liquid, after making it strongly alkaline, with ether codeinone was
obtained in crystalline form. Thus obtained the codeinone is con-
taminated with thebaine which is shown by the red color of its so-
lution in concentrated sulphuric acid. For purification the codeinone
was converted into its oxime, the latter dissolved in sodium hydro
xide, the alkali saturated with carbon dioxide and the precipitated
oxime recrystallized from alcohol.
2. The same codeinone can be obtained by digesting thebaine
for 17 days with cold normal sulphuric acid and working up the
product, in the same way as in 1.
S8 °
In both methods considerable codeinone is lost by the action of
the acid which converts it into thebenine and other products.
(Ber. 1906, 1409.)
R. Pschorr and W. Haas find that when thebaine is treated with
benzoyl chloride the products are similar to those which are obtained
by the action of acetic anhydride on a-methylmorphimethine or upon
thebaine, namely, derivatives of thebaol and of ethanolmethylamine
i.
Z'N, - f :
/ N.
('H: .O / 2
| 3.
1|
|4 |
I I () `N 2^
NA -
| H().CH2.0H2.NH(CH3)
/~ / Ethanolmethylamine
/ N/ -
|5 |
end" /
- I i :3. U. N
Sv/
Thoba Ol
The benzolthelbaol was prepared by digesting thebaine with
benzoyl chloride, mixing the reaction product with ether and remov-
ing the unchanged thebaine as hydrochloride with water. The excess
of benzoyl chloride was removed from the ethereal solution either
by shaking with dilute sodium hydroxide or by boiling with methyl
alcohol and distilling off the methyl benzoate in vacuum. The residue
of the ethereal extract containing the benzoylthebaol was recrystall-
ized from glacial acetic acid. A dibromide of this benzoylthebaol
was made by treating the benzoyl compound with bromine in
chloroformic solution, evaporating the solvent and, after boiling
the residue with alcohol, recrystallizing it from glacial acetic
acid. e -
When the benzoylthebaol is oxidized with chromic acid it is con-
verted into benzoylthebaolguinone which upon 'digestion with a 15%
solution of sodium ethylate loses the benzoyl group and is converted
into the sodium salt of thebaolduinone identical with the quinone
obtained by Freund which has the constitution of a 3.6-dimethoxy-
4-oxyphenanthraquinone

CH3. () s Z
\,,
Theba.olduinone
The ethanolmethylamine, H.O.CH2. CH2.NH(CH3), was prepared
by boiling the solution of thebaine in benzoyl chloride with alcohol
after dilution with water, filtering off from the benzoic acid and
other insoluble products which separate out on cooling and distilling
the filtrate with steam after making the liquid strongly alkaline
with sodium hydroxide. The volatile base was conducted into dilute
hydrochloric acid and identified as a chloraurate. (Ber. 1906, 16.)
Theobromine.
On adding an excess of theoloromine to a solution of lithium oxide
and evaporating under reduced pressure E. Dumesnil obtained theo-
bromine-lithium which can be regarded as theobromine in which one
hydrogen atom has been replaced by one atom of lithium. The
compound corresponds to the formula, C7H7N402 Li, and is soluble
in about half its weight of water. JExposed to the atmosphere the
solution of the compound becomes turbid from the separation of
theobromine and lithium earlyonate. Dilute hydrochloric acid decom-
poses the compound into free theoloromine and lithium chloride.
(J. pharm. chim., 1906, 326.)
Tobacco Alkaloids.
Amé Pictet gives a resumé of the investigations upon the alka-
loids of tobacco leaves. The dry leaves were macerated for a short
time in luke warm water and the extract then concentrated in
vacuum. From this aqueous extract, which contains about 10 per
cent of nicotine the latter is obtained by adding alkali to the extract
and distilling with steam. By fractionally distilling the crude nico-
time two other bases were obtained, of which one has the formula,
C4H9N and goes over below 100°, the other having a slightly higher
boiling point than nicotine is isomeric with nicotine and was named
90
nicotinine. By shaking out the alkaline aqueous liquid from which
the nicotine has been removed with ether two other bases were ob-
tained which were separated from each other by fractional distilla-
tion. One of these bases having the formula, C10H12N2, contains
two atoms of hydrogen less than nicotine, is liquid and was named
nicoteine; the other is solid, has the formula, C10H8N2, and was
named nicotelline. The relative amounts of these alkaloids in the
extract of the tobacco leaves are as follows: For 100 grams of
nicotine, the extract contains 2 grams nicoteine, 0.5 gram nico-
timine, 0.1 gram nicotelline and 0.2 gram of the base, C4H9N.
The author thinks that besides these alkaloids there are in
tobacco leaves still other bases and that different varieties of tobacco
contain different other alkaloids.
Nico'ſ INE. The chief reaction which helped to clear up the con-
stitution of nicotine was the oxidation of the alkaloid either by
chromic acid (IIuber, Ann. 141, 271), or by potassium ferricyanide
(Calhours and Etard, I8ull. Soc. chim. 34, 452), or by the successive
action of bromine and barium hydroxide (Pinner, Ber. 26, 292).
Chromic acid oxidizes nicotine to nicotinic acid (8-pyridine carboxylic
acid) showing that nicotine is a derivative of pyridine containing
the group, (; H 10.N, instead of a hydrogen atom in 8-position
('H
HC, / |-ton
|
H(; ; / CH
N &
N
Nicotinic acid
As the radical C5H10 contains one hydrogen atom less than
piperidine it was supposed to be piperidyl pyridine.
N II
/N
H2C/ NCH2
(; II | |
S. | |
HC/ C—HCN /CH2
HCN /on
N
N
IPiperidiſpy ridine.
NH
91
When oxidized with chronic acid nicotine loses 4 hydrogen atoms,
giving a compound of the formula C10H10N2 which is optically in-
active and unlike nicotine is a monoacid base. The removal of 4
hydrogen atoms destroys the asymmetry of the carbon atom and
changes the diacid nicotine to a monoacid base. The new compound
was named at first isodipyridine (in order to distinguish it from
dipyridine) and was assigned the constitution of a dipyridyl,
C5H5N-C5H5N. When oxidized with bromine and barium hydroxide
nicotin breaks up into nicotinic acid, malonic acid and methylamine.
This indicates that there is in nicotine a methylimide group and
that the other 4 carbon atoms form a normal chain of a pyrrol ring.
For this reason Pinner (loc. cit.) proposed the following formula for
nicotine
H2.0 CH2
CH | |
| |
HC/ C—CII . , CH2
| N.CIIa
HC , CH
Nicotine.
regarding the alkaloid as 3-pyridyl-N-methylpyrrolidine. The above
isopyridine would therefore be 3-pyridyl-N-methylpyrrol having the
following formula:
| IC CH
CH
/N
Ho/\c—d ºn
| Neil
N.CII:
i |
lic , ch
N
B-Pyridyl-N-methylpyrrol (Nicotyrine).
This would explain the optical inactivity of the compound as
well as why the base is monoacid (pyrrol, unlike pyrrolidine, having
extremely weak basic properties). The name of isodipyridine was
therefore changed to nicotyrine. The correctness of the above for-
mula of nicotine was corroborated by synthesis. The synthesis con-
sists of three parts: the synthesis of hicotyrine (3-pyridil-N-methyl-
pyrrol), the conversion of nicotyrine into inactive nicotine and the
splitting up of the latter into the active components of which the
laevo modification is identical with natural nicotine. The synthesis of
nicotyrine was carried out as follows. Nicotinic acid was converted
a 92
by means of Hofmann's reaction into 3-amidopyridine and the latter
distilled with mucic acid. The resulting 3-pyridyl-N-pyrrol when
passed through a red hot tube is transformed into 3-pyridyl-a-pyrrol
CH
/N - - - - - - - •
HC/ NC-NH2 HO.CO—CH.OH–CH.OH
+ - = 4H2O + 2CO2 +
HO /CH2 II (). ("()–(H.OH-CH.OH *
`º - -
H(! CH
(; H . CH CH - 9. -
/ - \, - / ------- N * . i - -
HC/ C—N/ HC/ \c—dº /on
| ` ——P | | N
s --- :- | | H NH
IICS (H ("H (;H HCN ^CH
º sº
N N
3-P yridyl-N-py rroi. |3-P yridyl-(1-pyrrol.

The 3-pyridil-a-pyrrol forms a potassium salt which when treated
with methyl iodide is converted into nicotyrine.
In order to reduce the pyrrol ring without reducing at the same
time the pyridine nucleus the nicotyrine was treated with bromine
which enters only the pyrrol ring and the resulting compound re-
duced with tin and hydrochloric acid. At first only two atoms of
hydrogen are taken up with the formation of dihydronicotyrine but
when the bromination and subsequent reduction was repeated the
compound was converted into tetrahydronicotyrine or inactive
nicotine identical in every respect with the inactive nicotine which is
formed by heating nicotine sulphate (or hydrochloride) in aqueous
Solution for 40 hours to 200°. -
The splitting up of inactive nicotine into its active components
was accomplished by the fractional crystallization of the bitartrates.
On mixing one molecule of inactive nicotine with a concentrated
solution of two molecules of dextro tartaric acid in water, the déxtro
rotatory bitartrate of l-nicotime crystallizes out on standing and can
be purified by recrystallization from water until the melting point and
the optical rotation remain constant. When this bitartrate is decom-
posed by alkali l-nicotine is obtained identical with the neutral base.
From the mother liquor of the dextrorotatory bit artrate of
|-nicotine a base was obtained (by means of alkali) which when com-
bined with laevorotatory tartaric acid gave the laevorotatory bitar-
trate of d-nicotine. On treating this bitartrate with alkali d-nicotine
was obtained. -
93
Physiological tests showed that l-nicotine is about twice as
poisonous as d-nicotine. This is in accord with observations made
by other investigators in the case of optically active substances, for "
example, d- and 1-hyoscyamine and their racemic form, atropine.
NICOTEINE. Like nicotine, nicoteine, C10H12N2, is a colorless
strongly alkaline liquid base miscible with water in all proportions
and not solidifying at —80° in a mixture of ether and carbon
dioxide. Nicoteine boils at 266—269°, has a specific gravity of
1.077 at 12°, a parsely-like odor and a specific rotation of [a] p 17 =
—46°. While the salts of l-nicotine (natural nicotine) are . dextro-
rotatory those of nicoteine are laevorotatory. An investigation of
the constitution of nicoteine showed that it is isomeric with dihydro-
nicotyrine obtained by reducing nicotyrine. As nicotyrine contains
the group, —CH=CH-CH=CH-, which by reduction usually changes
to the group, —CH2—CH=CH-CH2—, the formula of this syntheti-
cal dihydronicotyrine must be as follows:
{} HC CII
("H |
|
/ | | ©
II(2 Nc-1. S /
/
N.CII;
IICN y CH
ºv/
N
Dihydronicotyrine (synthetic).
. (3)
Nicoteinie can therefore have either of the two following formulas:
ILC CH2 H2C_ CH2
CH ("H
/N * /
HC/ \C—-CN /CH3 OI IIC, « ». º y CH2
N {
| N.CH3 º | N.CII;
HCN / CH HCN CII
Nº. 2' N
N NII
(1) (2)
As nicoteine being optically active must contain an asymmetric
carbon atom, formula 2 must be the correct one. When nicoteine is
heated in aqueous solution with silver oxide it is not oxidized but
is isomerized to dihydronicotyrine, i. e., (2) changes to (3). In
physiological respect nicoteine resembles nicotine but is slightly more
poisonous and does not produce contraction and lowering of the
temperature of the extremities.
94.
NICOTIMINE, C10H14N2. This alkaloid is isomeric with nicotine
and resembles the latter in physical properties like odor and boiling
point. Chemically it differs from nicotine in being a secondary base.
It was separated from nicotine by treating their mixture with
benzoyl chloride in alkaline solution or by nitrous acid. Both the
nitrosamine and the benzoyl derivative of nicotimine still possess
basic properties. As nicotimine does not give the pyrrol reactions
it is supposed to have the constitution of 3-pyridyl-a-piperidine, i.e.,
the constitution formerly ascribed to nicotine.
CH2
/N
H2C, N CHI 2
(! H |
t / x * & º t ! *
II ('A' | C–—IICN / CH2
i. | NZ
NII
HC ZCH
N/ g
N &
Nico timine.
NICOTELLINE, C10Hs N2. This alkaloid forms prismatic crystals,
melting at 147–148° and boiling a little above 300°. It is difficultly
Soluble in water or ether and its a gueous solution has a neutral
reaction. It does not give the pyrrol reactions and does not
decolorize potassium permanganate in acid solution. It is the only
tobacco alkaloid that forms a difficultly soluble chromate. In many
of its properties it resembles the dipyridines but is not identical
with either of the 4 known dipyridines of which 6 are theoretically
possible.
THE BASE CAHON. This base is obtained by distilling crude
nicotine and collecting the fraction that goes over between 80° and
90°. It is a colorless, very mobile liquid of a strongly alkaline
reaction and a piperidine-like odor. It was found to be identical
with pyrrolidine
II 20 (XH2
|
1120S / (‘II 2
/
NH
It is the presence of this very volatile base that gives to ordinary
nicotine the disagreeable ammoniacal odor which disappears upon
rectification.
As by boiling nicotine for 7 hours with a 20 per cent solution of
sodium hydroxide no pyrrolidine is formed it must be assumed that
95
pyrrolidine exists as such in tobacco leaves and is not formed from
nicotine during the distillation with alkali. Pyrrolidine would there-
fore seem to be the simplest vegetable alkaloid both with regard to
formula and constitution. (Arch. Pharm., 1906, 375.)
Tropeines.
H. A. D. Jowett and A. C. O. Haun show that the previously
observed dinimution in physiological activity of pilocarpine upon
the addition of potassium hydroxide also occurs in the case of
terebyltropeine and phthalidecarboxyltropeine.
(CII.3)2.0——CH.C.O.P
('H. ("(). I?
OS y^CH2
&=7 * as " )
\!/ ( (s II l J/ (
("() ("()
Terbyl tropeine. I?hthalidecarboxyl tropeine.
(I) (II)
(P stands here for the nitrogen — containing nucleus.)
It is also shown that Ladenburg's generalization that only those
tropeines have mydriatic action which contain a benzene nucleus in
the acyl complex does not hold good in the case of terebyltropeine
which has a distinct mydriatic action. In general it was found that
the most favorable conditions for the developement of mydriatic
action in a tropeine are those stated by Ladenburg, namely, that
the acyl group should contain a benzene nucleus and an aliphatic
hydroxyl in the side chain containing the carboxyl group. This is
shown by the fact that three other tropeines, namely, protocate-
chyltropeine, methylparaconyltropeine and glycollyltropeine had no
mydriatic action at all.
Glycollyltropeine, CH2(OH).(O.C.s H140N, was prepared by La-
denburg’s general method (Ann. 1883, 217, 82) and purified by
converting it into the hydriodide, recrystallizing the latter from
methyl aleohol, then setting the base free and recrystallizing it from
benzene. The tropeine forms laminar crystals melting at 113–114°,
which are soluble in alcohol and water, but insoluble in ether. The
hydriodide separates from methyl alcohol in stout acicular erystals
melting at 187—188°, which are soluble in water, difficulty soluble-
in alcohol, and insoluble in ether. It contains half a molecule of
water of crystallization which cannot be removed by heating to
110°. Higher temperatures decompose it. A nitrile melting at
120–121°, an aurichloride melting at 186–187° and a plantini-
chloride melting at 225–226° were also prepared.
96
Methylparaconyltropeine,
('H3. (H– () H.C.O.C.s H1 (ON
|
O.(O.(H2
as well as the remaining tropeines described in this paper, was pre-
pared by passing hydrogen chloride through a solution of tropine
neutralized with the acid in question and maintained at a tempera-
ture of 120–125° for two to three hours (Täuber, D. R. P., 95,853).
The dark brown gum thus obtained was decomposed by ammonia
and the base extracted with chloroform; the crude tropeine was
purified by conversion into the hydriodide. The pure base, regener-
ated from the hydriodide, forms a colorless oil. A hydriodide of
this tropeine melting at 177–178°, a hydrobromide melting at
196–197°, an aurichloride melting at 64–65° and containing one
molecule of water of crystallization, an amorphous platinichloride
melting at 23.3—23.4° and a picrate melting at 190—191° were pre-
pared.
Terebyltropeine (I) forms diamond-shaped crystals melting at
66–67°, which are easily soluble in water or alcohol. A lydro-
chloride in the form of leaflets which soften at 80° and melt at 82°.
a hydrobromide in the form of laminar crystals melting at 230° to
231°, an aurichloride forming imperfect crystals which melted in-
definitely at 85–86° and contained a molecule of watter of crystal-
lization, a gelatinous platinichloride and a picrate, melting at 198°."
to 199°, were prepared.
I’hthalidecarboxyltropeine (II) was purified through the hydro-
bromide and recrystallized from ethyl acetate. It crystallizes in
square, laminar crystals melting at 79–80° and forms a hydro-
chloride melting at 79–80° and forms a hydrochloride melting at
242–244°, a hydrobromide in the form of glistening leaflets melting
at 128–129°, a nitrate containg a molecule of water of crystalliza-
tion and melting at 169—171°, an aurichloride melting at 184–185°
and an amorphous platinichloride melting at 235°. t
Protocatechyltropeine, Co Ha(OH)2.('O.C.s H140N, forms stout aci-
cular crystals which are sparingly soluble in water or alcohol and
melt, at 253–254°. It forms a hydrochloride which does not melt,
below 300°, a nitrate which is so easily oxidizable that it was not
further investigated, an easily reducible aurichloride, a platini-
chloride melting at 228—229° and a picrate melting at 260–262°.
(J. (Shem. Soc., 1906, 357.)
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Pin kroot and its Substitutions.
3. * **
tº' y
3;
w” sº
Bºw. W. STOCKBERGER.
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1907.
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No. 16.
e MIL WAUK E E,
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Pinkroot and its Substitutions.
By W. W. STOCKBERGER.
MULVVAUKEE,
Pharmaceutical Review Publishing Co.
1907.
Fig. 1. PINKRoot (SPIGELIA MARILANDICA L.).
Stockberger, Bulletin No. 100, Part V, Bureau of Plant Industry, U. S. Dept. of Agr.

Fig. 2. EAST TENNESSEE PINKRoot (RUELLIA cluosa PURSH).
Stockberger, Bulletin No. 100, Part V, Bureau of Plant Industry, U. S. Dept. of Agr.


*:::::::::.
4 - a ” *
INTRODUCTION.”
The object of this paper is to trace the beginning and develop-
ment of the confusion concerning the drug known as pinkroot, which
has made it possible for an entirely unrelated product of extremely
doubtful efficiency to masquerade successfully before the drug expert
as well as the drug dealer for many years as the genuine article and
well nigh drive the latter out of commercial existence. A specific
illustration is furnished of the possibilities of obtaining reliable
results in revising and extending our knowledge of the authenticity
and the sources of our crude drugs through their study under
cultivation.
For the purposes of scientific experimentation on the action of
drugs in health or in disease the absolute identity of the material used
is obviously necessary. To secure the desired results in his practice,
the physician must feel confidence in the source of the medicinal sub-
stances used. Crude drugs as they ordinarily occur in the market
fail too frequently to fulfill this requirement through the confusion of
the plants concerned or through the willful introduction of sophistica-
tions.
Hundreds of tons of crude drugs are produced and consumed an-
nually in this country. Manifestly substitution or adulteration in
this product is a standing menace to the public health. Yet, as this
paper sets forth, plants of unknown und possibly deleterious proper-
* This paper was prepared by Mr. W. W. Stockberger, Expert in Drug Plant
Investigations in the laboratories of the Bureau of Plant Industry. U. S. Depart-
ment of Agriculture. . A brief synopsis of the subject matter of the paper was
rinted October 9, 1906, as Bulletin No. 100, Part V, of the Pureau of Plant
ndustry. The publication of the complete paper in the Pharmaceutical Review has
been approved by the Honorable Secretary of Agriculture.
R. H. TRUE, Physiologist in Charge.
Some time after this work was in manuscript Mr. Theo. Holm published an
interesting article on the root structures of Spigelia, Phlox, and Ruellia, (Amer.
Jour. Pharm., Dec. 1906) in which he fully confirms the conclusions reached in this
paper.
2 PINKROOT AND ITS SUBSTITUTIONs.
ties may so far replace an official drug plant as to be confused with
the real drug and in its stead be made the basis of study and ex-
periment.
Only through cultivation and by bringing the plants to maturity
for exact identification was it possible to determine with certainty the
interrelationship of the pinkroot, Spigelia marilandica L. (Fig. 1),
and its adulterants, a method of procedure which recommends itself
in all critical study of drug plants.
HISTORY.
FIRST DESCRIPTIONS OF TILE PLANT SPIGELLA.
The plants known by the name of pinkrooi, and widely famed
for the anthelmintic virtues of which they were the reputed posses-
sors, had long been known to botanists and described by them under
various generic names before they were erected into the present genus
Spigelia by Linnaeus. The species now known under the name
Spigelia anthelmia L. was the first to be noticed and was described by
Marcgraf in 1648 and in his “Historiae Plantarum” under the name
Arapabaca. The exact locality from which the plant was collected
and described is not known, as he says simply “a plant called Arapa-
baca in Brazil.” His account embraces merely a very brief botanical
description, as is usual with the early authors. No statement of the
distribution of Arapabaca or of its properties is given, but the descrip-
tion is supplemented by a very good colored plate which shows the
general botanical characters of the plant and renders its identity
certain.
In 1703 Plumier,” in describing new American plants, referred
to and quoted Marcgraf’s description of Arapabaca. He has been
erroneously referred to by Periera and by Romyun as the first author
to mention the Spigelia anthelmia. The latter author perpetrates the
error in an article the purpose of which was to establish the prior
claims of S. anthelmia on the notice of the scientific world.
According to Bergius * a contemporaneous description of this
1 Marcgraf, G. Historiae Rerum Naturalium Brasiliae. Historiae Plantarum,
vol. 1, p. 34, 1648.
2 Plumier, C. Nova Plantarum Americanarum, Genera, p. 1 1 , Paris 1703.
3 Bergius, T. J. Materia Medica e Regno Vegetabili, vol. 1, pp. 93–95, Stock-
holm, 1778.
HISTORY. 3
plant was made by Hernandez in his work on Mexican medicinal
plants in 1651, where he describes under the name “Xivhtotonqui, seu
herba calida Totopocensi” a plant to which he ascribes numerous
remedial properties. Since no other author mentions this plant as
synonymous with Spigelia anthelmia, and as Hernandez's figure of
the plant is almost devoid of characters suggesting Spigelia, his de-
Scription of its properties also including a number not possessed by
that plant, we must regard the correlation of Bergius as very doubt-
ful. At all events his description is antedated by that of Marcgraf.
Not far from the time when Plumier commemorated Marcgraf’s
name Arapabaca, another term was introduced by Petiver *, who gave
a short account of its botanical characters, and, because of the rela-
tionships of the plant as he understood them, called it Heliotropium
brasilicum.
Amid the sweeping changes in nomenclature made by Linnaeus *
in his Systema Naturae, Plumier’s genus Arapabaca disappeared, and
on it was founded the Linnaean genus Spigelia, so named in honor of
Adrien von den Spieghel, a Flemish botanist, a professor at Padua,
whose first work was published in 1606 and whose death occurred in
1625. It is stated in Woodville’s Medical Botany “ that the American
species was first called Lonicera by Linnaeus, but that he afterwards
ascertained its true characters and called it Spigelia in honor of
Spigelius. This, must refer to the addition of a new species, and not
to the founding of the genus as the reading indicates, since, as just
stated, the genus was founded in 1747, while the first mention of
Spigelia marilandica occurred in 1767.
In 1751, writing in the Gentleman’s Magazine, Browne * gives
an account of the properties and use of a plant which he called
Anthelmia. He says: “In some parts of the island of Jamaica grows
a small plant, known in the Windward Islands by the name of Worm-
grass, which I have taken the liberty of describing by the name of
Anthelmia, as it was a genus not before known in botany.” It ap-
pears that at the time this was written, Dr. Browne was not aware of
the work of Marcgraf and of Linnaeus, by whom the genus was
65i Hernandez, F. Rerum Medicarum Novae Hispaniae Thesaurus, p. 201, Rome,
} ſº
2 Petiver, James. Gazophylacii Naturae et Artis, etc. tab. 59, 1702–1709.
8 Linnaeus, C. Systema Naturae, ed. 2, p. 25, 1747.
4 Woodville and Hooker. Medical Botany, ed. 3, p. 179, 1832.
5 Browne, Patrick. Account of the Anthelmia, Gentleman's Magazine,
21 : 544–546, 1751,
4 PINKROOT AND IT's SUBSTITUTIONs.
founded, and that the same plant had been described by Büttner as
“Spigelia, ramis indivisis, etc.” Browne’s description, however, is of
interest because of the account of the medicinal properties and use of
this plant. Two years later Linnaeus', in his Species Plantarum,
described the first species of the genus Spigelia, and, recognizing that
the Anthelmia of Browne was the same as the Arapabaca of Marcgraf,
gave it the specific name anthelmia, since which time the generally
accepted name for the plant has been Spigelia anthelmia I.
Tn 1756 Browne * published an account of this species under the
name Anthelminthia quadriphylla. The change in the generic name
from the Anthelmia of his earlier account was made possibly to sug-
gest more readily its anthelmintic properties. The Spigelias of
Büttner and of Linnaeus were recognized as synonyms, as was also
the Arapabaca of Marcgraf and Plumier. It is stated that this plant
grows naturally in most parts of South America and that it was cul-
tivated in the gardens of Jamaica. Ilater observations on the flora of
this island have shown that the plant is indigenous to Jamaica. In
addition to the botanical description of the plant, an account of its
use and medicinal properties is given.
The common names of this species are not without interest, and
deserve mention here, since they reflect something of the history of
the species and also suggest in several cases the properties which the
plant is reputed to possess. Thus we have Arapabaca, Cumana,
loggerhead weed ; Demerara pinkroot, and West India pinkroot, sug-
gesting locality; Brinvilliers, the term applied by the French, refers
to its poisonous properties, while its medicinal properties are indi-
cated by Spigelie anthelmintique, worm-grass, Yerba de Bombrices,
Yerba de lombrices, poudre a vers, and Iombricera blanca.
In the year 1704, fifty-six years after Marcgraſ had described
Arapabaca, John Ray " published the description of a new plant
which afterwards became the second species in the genus Spigelia
under the name Spigelia marilandica. The first botanical description
of this plant as set forth by Ray in his Dendrologiae is as follows:
“Periclymeni Virginiani flore coccineo planta Marilandica
spicata erecta foliis conjugatis. D. Sherard.”
1 Limnaeus, C. Species Plantarum, Vol. 1, p. 149, 1753.
l 2 #ºwne, Patrick. The Civil and Natural History of Jamaica, p. 156, Lon-
ClOn, 1756.
3 Ray, John. Historiae Plantarum, vol. 3, Dendrologiae 3, No. 23, p. 32,
Ilondon, if 04,
---
HISTORY. à
It is very probable that Ray received his specimens from Sherard
and appended his name to the description as an acknowledgment of
the source from which he obtained the plant, since there is no mention
of Spigelia in the writings of Sherard. The plant had been under
cultivation in England for some years prior to Ray’s description, but
there is no earlier reference to its systematic place by other authors.
Several facts of importance in the history of Spigelia marilan-
.dica are to be noted in the work of Catesby * on the Carolinas. In his
description he assigns a new systematic place to the plant, as follows:
Gentiana forte? quae Periclymeni Virginiani flore coc-
cineo, etc.
Catesby cites the work of Ray just mentioned and is the first to
give the common name by which the plant was known in its native
habitat. This is stated to be the Indian pink, and a somewhat de-
tailed description of the botanical characters of the plant and a good
colored plate are features of the work. Concerning the cultivation of
the plant Catesby further says: “This Plant was in Blossom, the
First of August 1738, in the garden of Mr. Christ. Gray at Fulham,
and endures the Winter without any Protection.”
In an account of the flora of Virginia some years later Grono-
vius * gives this plant the name Lonicera, the name which was first
used by Linnaeus. Under the Pentandria monogynia of Gronovius
occurs this description:
“Lonicera spicis terminalibus, foliis ovato-oblongis acuminatis
distinctis sessilibus. Fl. Virg. 142.”
The previous descriptions of Ray and Catesby are cited and re-
garded as synonymous. Simply the botanical description is given;
there is no reference to distribution or properties.
In a letter written about 1754, Dr. John Lining * discusses the
Indian pink and in his formula for its medicinal use refers to it as
“Rad. Anthelmiae (for so I called the Indian pink).”
In an abstract and summary of this letter in the Amoenitates
Academica: “ this term is referred to and attention called to the fact
1. Catesby, Mark. The Natural History of Carolina, Florida, and the Bahama
Islands, vol. 2, p. 78, London, 1743.
2 Gronovius, D. Flora, Virginica, ed., 2, p. 30, Leyden, 1762.
8 Lining, J. Of the Anthelmintic Virtues of the Root of the Indian Pink.
Essays and Observations Physical and Literary, vol. 1 , Art. XIV, pp. 386–889,
Edinburgh, 1754. sº
175s, Colliander, J. G. Spigelia Anthelmia. Amoenitates Academićae 5: 133–147 .
ſ tº
(5 PIN KROOT AND ITS SUBSTITUTIONs.
that the Anthelmiae of Lining is not the same as the Anthelmia of
Browne. This point was further emphasized by Dr. Garden a few
years later in his letter to Dr. Hope, when in observation 2, after the
description of the Indian pink, he says: “also the five-lobed calyx,
the structure of the limb and anthers, the articulated style belonging
to this, separate it from Spigelia.” The Spigelia here referred to is
the Anthelmia, or the Spigelia of Linnaeus in the sense in which those
terms were used by Browne *. g
The name Lonicera introduced by Gronovius was adopted by
Linnaeus *, and appears in his Systema Naturae as late as 1767. In
the body of this work (ed. 12, p. 166) the plant is referred to as
Lonicera marilandica. Later, however, after examining a specimen
of the plant with fruit sent to him by Dr. Hope, he decided that it
was a true Spigelia, and in the appendix to the same edition (p. 734)
gives the name under which it is now known, Spigelia marilandica.
INTRODUCTION INTO EUROPE.
The time of the first introduction into Europe of the two Spi-
gelias is somewhat obscure. Confused with the early botanical ac-
counts of these plants are the references to the discovery of their
medicinal properties, and thus there have arisen divergent statements
concerning their early introduction and use.
Bobart is said to have cultivated Spigelia marilandica in Eng-
land in 1694. This was ten years before its first description botani-
cally and nearly fifty years before observations on its medicinal pro-
perties were recorded by Europeans.
The earliest authentic date of the introduction of Spigelia anthel-
Inia is that given in Johnson's Gardener’s Dictionary ". Here it is
stated that the S. (in lhelmia was introduced into cultivation in 1759.
This was several years after attention had been called to the medicinal
properties of the plant by Browne. Sprengel", in the chronological
tables of his History of Medicine, assigns 1739 as the date for the
introduction of Spigelia marilandica and S. anthelmia. IIis authority
for this date is not mentioned, but it may have been inferred from
1 Garden, A. An Account of the Indian Pink. Essays and Observations Phy-
sical and I,iterary, vol. 3, Art. X, pp. 5–1 ; ; ;3, 1771.
2 Browne, I?. Gentleman's Magazine, 21 : 54-4, 1751.
3 Ilinnaeus, C. Systema Nature, ed. 12, vol. 2, p. 1 (56, 734, Stockholm, 1767.
: Aiton, Wm. Hortus Kewensis, 1 : 202, London, 1789.
6
Johnson's Gardener's Dictionary, p. 920, new ed., London, 1894.
Sprengel, Kurt. Histoire de la médecine, 4:43 l, Paris, 1815.
HISTORY. 7
Catesby’s work, published in 1738. The earliest date assigned by the
authorities cited in their historical accounts of each of these species
is 1748, the date mentioned by Browne for S. anthelmia.
From the records now available it appears that although the
Spigelia marilandica was discovered and described much later than
S. anthelmia, nevertheless it was introduced to cultivation in Europe
about fifty years earlier.
DISCOVERY OF MEDIC [NAL PROPERTIES.
The anthelmintic properties of Spigelia had long been known
and made use of by the native inhabitants of the West Indies, Central
America, and the southern United States before Europeans came to
a knowledge of its virtues. However, attention was early called to its
efficacy in checking what threatened to become an epidemic of dis-
orders among the slaves of the planters in the British colonies, due, as
was supposed, to the presence of worms induced by the hardships,
coarse diet, and irregular habits of living of the slaves. Dr. Browne *
states that in 1748 these disorders reached such a height as to
threaten the ruin of many of the planters by the loss of their slaves.
He introduced the Spigelia anthelmia in his practice at that time and
after observing its good effects in curing many cases which it was
feared would terminate fatally, he was so impressed with the value of
the plant medicinally that he felt constrained to make public its
description, effects, and the manner of its use. Hughes *, whose work
appeared a year earlier than that of Dr. Browne, also refers to the
early use of this plant and commends it as a powerful anthelmintic.
The earliest mention of the vermifuge virtues of Spigelia mari-
Handica is that made by Catesby * in 1743. After describing this plant,
which he calls the Indian pink, he says: “A Decoction made of this
Plant is good against Worms.” It seems to have been known to the
medical profession and in general use as a domestic remedy for a long
time prior to the publication of Catesby’s work, for in a letter written
by Dr. Lining ", of Charleston, S. C., to Dr. Whytt, in 1754, it is
stated that: “It has been for many years used in this part of the
: Bººk."gº"Magazine. l. c., 1751.
Šºši. **śi º","ä"London, 1743.
Lining, J. Fºssays and Observations Physical and Literary, 1: 386, Edin-
burgh, 1754.
:
8 PIN KROOT AND ITS SUBSTITUTIONs.
world, not only by all the practitioners but likewise universally by the
planters.” Another Charleston physician, Dr. Garden', in his first
letter to Dr. Hope, which was written about 1763, says: “About forty
years ago the anthelmintic virtues of the root of this plant were dis-
covered by the Indians, since which time it has been much used by
physicians, practitioners, and planters.” From this it appears that
the Indians communicated a knowledge of its properties to the whites
about 1723. How long they had possessed this knowledge can not be
determined, but evidently they had used the plant long enough to
have a very high regard for its virtues, for according to Barton *
“The Cherokee Indians have so high an opinion of this plant, that it
would sometimes be dangerous for a person to be detected digging it
up, to carry it out of the country.” 3.
By the letters of Lining and Garden, the medicinal properties of
Spigelia marilandica were widely exploited in Europe, about 1754,
and, largely on the authority of these practitioners, who reported such
excellent results attending its use, it was admitted to the London
Pharmacopoeia in 1788.
º
EARLY CONFUSION OF SPIGELIA ANTIILLMIA AND SPIGELIA MARI-
IANDICA.
The almost simultaneous introduction into Europe of Spigelia
amlhelmia and S. marilandica as anthelmintics caused them to be
frequently mistaken one for the other. No doubt Dr. Lining was
acquainted with the account of the Jamaica species by Dr. Browne,
for in his writing on the one used in the Carolinas he designated it as
Anthelmia, the same term Dr. Browne had used in describing the
former. This similarity of name may account for the confusion with
regard to which of the plants Brocklesby * used so successfully in his
practice. Writing at London in 1764 he says: “In some cases * * *
ſoſ worms I had recourse to the Anthelmia or Indian Pink “ ” ”.
He was so impressed with its virtues that he recommended it to the
Faculty of London and says further: “Dr. Hinckley, one of the phy-
sicians to Guy's hospital, has prosecuted farther experiments with this
plant, which he calls Caryophyllum Americanum Anthelminticum.”
1771 Garden, A. Essays and Observations IPhysical and Iliterary, 3: I 45—153,
{ { l .
l 3. #ºn, B. S. Collections for an Essay towards a Materia, Medica, p. 38,
e(l. 3, 181 ().
3. Brocklesby, Richard. Oeconomical and Medical Observations, p. 282, Lon-
don, 1764.
HISTORY. 9
He credits Dr. Lining as being the first medical writer that he has
known to mention the anthelmintic virtues of the root. He was evi-
dently not acquainted with the writings of Catesby previously cited.
A number of medical writers, among whom are Sprengel, Woodville,
and Murray, probably influenced by the use of the name Anthelmia,
cite the statements made by Brocklesby as confirming the virtues of
Spigelia anthelmia, but a careful reading of his text discloses no
reference to that species. On the other hand, his use of the term
“Indian pink,” the reference to Dr. Lining’s work, and the name
given by Hinckley are evidence that he used the Spigelia marilandica,
and to this species his observations should be credited.
From the name proposed by Hinckley for this species may have
originated the term Radia caryophyllae, sometimes erroneously used
in dealers’ lists to denote Spigelia marilandica.
Another element of confusion between these two species was in-
troduced in 1823 when Feneulle * published a chemical analysis of
what was supposed by him to be Spigelia anthelmia, an analysis which
the dictum of later years accords to S. marilandica.
Feneulle's description of the roots used in his analysis furnishes
one of the strongest evidences that he had Spigelia marilandica. He
says: “Leur coleur est braune; elles ont une odeur aromatique peu
marquée; leur Saveur est amère, mais plus décidément astringente.”
Another consideration is his reference to the United States as the
place where its use originated, as follows: “La spigélie est la Spigelia
anthelmia de Linné, il parait que c’est aux Etas-Unis oil on a com-
mencé à l’employer.” Madiana , who had traveled extensively in
North America, never saw Spigelia anthelmia growing or in the col-
lections in the shops. He states that Spigelia marilandica is the only
species used in the United States, that the commerce of America only
furnishes a product with roots, stem, leaves, and flowers, which are
the subject of the work of Feneulle. He further states that Spigelia
anthelmia is not exported to Europe except perhaps in the form of a
sirup which is bottled by the negresses of the West Indies, and that it
keeps badly and is not in good repute with the medical practitioners
of the Continent.
1 Feneulle, H. Almalyse de la Spigélie anthelminthique. Journal de Pharmacie
et des Sciences Accessoires, 9 : 197, 1823.
* Ricord-Madiana, J. B. Recherches et Expériences sur les Poisons d’Amérique.
1er Mémoir Du Brillvilliers, F3 ordeaux, 1 S26.
1() PINKROOT AND ITs SUBSTITUTIONS.
Later times have brought the confusion of unrelated plants with
Spigelia marilandica through their introduction as adulterants. How
one of these, Ruellia ciliosa Pursh, has been figured and described as
Spigelia itself, and how Ruellia in turn has been mistaken for Phloa.
ovata L. (Phloa carolina L.) and so described and figured as an
adulterant of Spigelia, will be fully discussed later.
CIIEMICAL RESEARCIIES.
The first chemical study of Spigelia anthelmia was made by
Ricord-Madiana in 1826. That he had a plant different from the
one investigated by Feneulle appears from his statement of the ap-
pearance and properties of the roots, which were branched and hairy,
covered with a brown epidermis, white inside, and of a repellant odor.
The fresh root was not found to be bitter, acrid, and astringent as was
observed by Feneulle in the Spigelia examined by him.
The methods used by Madiana were the same as those employed
by Feneulle. All parts of the plant were subjected to analysis and he
determined in the leaves and in the root the following constituents:
Leaves: Chlorophyll, volatile oil, abundant mucus, wax, stea-
rin, gallic acid, a black gummy mass not bitter but nauseous,
lignin, malates of potassium, lime, and other mineral salts.
Roots: Fat, stearin, wax, resin in very small amount, mucus,
albumin, gallic acid, carbonate and chloride of potassium; sul-
phate, subcarbonate, and phosphate of lime; oxid of iron,
silicia, lignin.
Madiana notes especially the absence of a volatile oil and of a
bitter substance in which according to Feneulle the vermifuge action
resided.
Recently, in 1896, Boorsma made a careful study of Spigelia
anthelmia in search of an active principle which would account for
its toxic effects. He succeeded in isolating an alkaloid resembling in
its action gelsemine and strychnine.
In isolating the alkaloids Boorsma first sought for a volatile
active principle by distilling a mass of fresh herb and shaking out the
distillate with ether. After evaporation of the ether extract the resi-
1 Ricord-Madiana, l. c.
2 Boorsma, W. G. Nadere Resultaten van het (loor Dr. W. G. Boorsma, ver-
richte Onderzoek naar de plantenstoffen. Mededeelingen uit Buitenzorg’s lands
Plantentuin, XVIII, 1896.
HISTORY. | |
due consisted in part of feathery crystals soluble in acidulated water
and having a feeble reaction to the common alkaloidal reagents, but
possessing practically no poisonous properties. The liquid remaining
after the separation of the ether extract was acidulated and evapor-
ated to a small residue. This gave absolutely no alkaloid reactions
and also was not found to be poisonous. Boorsma therefore concluded
that the plant does not contain a volatile alkaloid. w
In his research for fixed alkaloids Boorsma used alcoholic ex-
tracts of the fresh plant which were partially soluble in water acidu-
lated with acetic acid. The aqueous solution was then purified with
basic lead acetate, concentrated by evaporation and shaken up with
chloroform so long as it would take anything from the alcohol. The
chloroform extraction was much more perfect when the solution was
made alkaline with ammonia. After evaporation the chloroform left
a brownish sticky residue, intensely bitter to the taste and largely
though not entirely soluble in acidulated water. It is insoluble in
pure water, ether, carbon disulphid, and petroleum ether.
Solutions of the alkaloid were not found to be very sensitive to
the general alkaloidal reagents. In a concentration of 1 per cent. Only
a slight cloudiness appeared. More abundant precipitates were ob-
tained by the use of iodin potassium iodid, and phosphotungstic acid.
It has no very distinctive color reactions. Nitric acid dissolves the
alkaloid with the development of a yellow color. Sulphuric acid with
cerium oxid gives a dirty brown coloration, as does also Fröhde's
reagent and sulphuric acid.
The alkaloid was extremely bitter, and physiological tests showed
that it possessed remarkable toxic properties. On frogs it produced
not tetanic but spinal paralysis. The hypodermic injection of 0.5 mg.
was found to be lethal to guinea pigs.
As Dudley had already used the term “spigeline” to designate
the new volatile alkaloid isolated by him from Spigelia marilandica,
Boorsma proposed for the alkaloid isolated by him from Spigelia an-
thelmia the name “spigeliine.”
Within recent years another species of Spigelia has attained a
place in the Mexican Materia Medica ". This is Spigelia longiflora
Mart. & Gale, known to the natives as “sangre de Toro” and “Yerba
1 Nueva Farmacopea Mexicana, ed. 3, p. 94, 1896.
12 PIN KROOT AND ITS SUBSTITUTIONS.
del burro.” It is used medicinally as a succedaneum for S. anthelmia.
Cordero has studied the chemistry of the plant and finds a volatile
alkaloid by the same methods used by Schloessing in isolating nico-
tine and by Dudley in obtaining “spigeline.” A very small quantity
of the plant extract proved very poisonous to animals. Its extremely
poisonous properties have prevented the collection of any positive data
as to its value as an anthelmintic. It is believed that the risks at-
tending its use as such are not compensated by the possible good
effects to be obtained.
Spigelia marilandica has been the subject of several chemical
researches, the first of which was made by Feneulle in 1823. Wacken-
roder *, Stabler *, Dudley ", and Boynton " have also made proximate
analyses of this plant, but their results are discordant and their work
on the whole yields but an imperfect knowledge of its chemical pro-
perties. A somewhat detailed account of these researches is given
later in the account of the true pinkroot.
ORIGIN OF TRADE WARIETIES OF PINKROOT.
The species of pinkroot (Spigelia anthelmia) which early al-
tained great repute as a domestic medicine among the natives and
laborers of British Guiana, particularly along the east and west coasts
of Demerara and on the banks of the rivers there, received the name
T]emerara pinkroot, a term which is yet frequently used when it is
desired to distinguish this species from the pinkroot occurring in the
United States. Mention is made of this species by Bonyun ", who
states that in preparing this plant for sale it is pulled up by the roots
in a green state and the seeds stripped off, and then it is carefully
cleaned, dried in the sun, and packed in bundles.
The variable and sometimes poisonous action of the Spigelia
marilandica has frequently been attributed not to the presence of
harmful substances in the plant itselſ, but to its admixture or adul-
teration with other roots possessing deleterious properties. In 1819
Ewell ', after reciting a case in which the use of the Carolina pink-
root had been followed by an affection of the eyes, says: “Then use
; º; 1894.
8 Stabler, R. H. On Spigelia. Proc. A mer. Pharm. Assoc., 6: 132–134, 1857,
jou'. ºf Ysgºlºary Notice of a New Volatile Alkaloid. Anner. Chem.
5 Boynton, W. C. Laboratory Notes. Amer. Jour. Pharm., 56: 570, 1884.
6 Bonyun. On Spigelia Anthelmia. Pharm. Jour., 5 : 35 t—355, 1846.
7 Ewell, James. The Medical Companion, p. 605, 1819.
HISTORY. 13
the tops only, as it is supposed the deleterious effects are in conse-
quence of some other root being attached to it.” After discussing the
probability of the Carolina pinkroot possessing poisonous properties,
Kost says: “It is also remarked that all the bad effects that have
been observed in the use of this article have been caused by another
plant which is inadvertently or fraudulently collected and sold mixed
with the spigelia.” It is thus evident that the idea was early preva-
lent and growing that much of the so-called Carolina pinkroot for
sale in the drug markets was adulterated with some other plant of
unknown origin.
A tacit admission of the substitution of some plant with un-
known but probably harmful properties is made by Brown “, when on
prescribing a tincture of pinkroot in a worm mixture he says: “Be
cautious to get good pinkroot, as much of the plant sold for pinkroot
by the druggists is poisonous.” In the early sixties it was observed
that the invoices of pinkroot received from Tennesse were composed
largely of an unknown root which was recognized as differing essen-
tially from Spigelia. So persistently was this root offered as pink-
root by the collectors of Tennessee that it soon formed a trade variety
which was indicated by the name Tennessee pinkroot or East Ten-
nessee pinkroot, a term which is still in use by dealers in crude drugs.
The late Professor Maisch * stated in 1883 that the Spigelia
which was commonly sold twenty-five years before had entirely dis-
appeared from the market and that its place had been taken by the
much smaller roots of Spigelia marilandica and by one or more
species of Phlox. Some have inferred from this change in the ap-
pearance in the crude drug that Spigelia anthelmia was first used in
the United States and was afterwards supplanted by Spigelia mari-
landica. That this was not the case becomes evident when it is
noted that Spigelia anthelmia was not known in the United States,
that it was not an article of commerce, and that clear evidence of the
knowledge and use of the Spigelia marilandica is afforded by the
writings of Garden, Lining, and others.
When the source of supply from the Southern States was cut off
by the civil war it is not improbable that the major part of the market
supply at the north was obtained from Tennessee, and since the roots
Tº rost, J. The Elements of Materia, Medica, and Therapeutics, p. 355, 1858. ,
2 Brown, O. Phelps. The Complete Herbalist, p. 195, 1867.
8 Amer. Jour. Pharm., 55: 631, 1883.
|-| PIN KROOT AND ITS SUBSTITUTIONs.
of robust specimens of East Tennessee pinkroot are larger than those
of Spigelia, Profesor Maisch may have had material from that source
in mind when he referred to the size of the roots.
TIl FORY TITAT TITE CAROLINA P.III.OX WAS AN ADULTERANT.
Responsibility for the probably erroneous statement that species
of Phlox, particularly Phloa ovata L. (Phloa carolina L.), were sub-
stituted for Spigelia can not be fixed with certainty. The Wallace
Brothers, of Statesville, N. C., are said to have identified the East
Tennessee pinkroot under the above name. Professor Hyams claimed
that he had made a similar identification for which he had not re-
ceived due credit. Maisch had in his collection samples labeled in a
manner indicating that he believed them to be Phlox. Recent in-
vestigations, however, show quite clearly that Phloa ovala does not
occur as a substitute for Spigelia. This subject is discussed in some
detail under the head “Minor Adulterants of Spigelia,” and the
botanical source of the false pinkroot is shown to be a species of
Ruellia in the discussion of “East Tennessee Pinkroot.”
ANATOMICAL STUDIES.
The plant family Logamiaceae to which the Spigelias belong, has
been the subject of numerous and extensive researches. The Spigelias,
however, have been much less studied than other allied genera, as
Strychnos, for example, and then frequently only as accessory to some
other work. The formation of internal phloem in the Loganiaceae
was pointed out in 1875 by Vesque *, but he laid small stress on this
phase of his observations. He states that this tissue is composed of
bast parenchyma and very large sieve tubes extending far into the
pith. Hérail devoted a large part of his research on the anatomy
of the stem of dicotyledons to the internal phloem, for which he pro-
posed the name “liber médullaire,” for he believed that it was always
medullary in origin. With respect to the Loganiaceae he says that
the normal phloem is always much reduced, not to say wanting, in
certain species. Outside of this occurs the pericycle forming a band
composed of numerous layers of cells. Those of the exterior are
1 .*.*. J. Mémoire sur l'Anatomie Comparé de l'Écorce. Ann. Sci. Nat.
Bot., sér. 6, 2: 82–198, 1875.
2 Hérail, J. Recherches sur l’Anatomie Comparée de la Tige des I)icotylédones
Ann. Sci. Nat. Bot., Sér. 7, 2:20:3–314, 1885.
HISTORY. |; )
sclerified and form a ring of sclerenchyma which has been described
as a character distinctive of plants of this family.
Perrot suggested the term “perimedullary sieve tissue” for the
anomalous tissue occurring around the pith in the Loganiaceae. He
cites the well-known fact that this tissue is not always continuous
around the pith, but occurs often in large isolated masses. In some
tribes of the Loganiaceae it is lacking. These isolated masses increase
in size by division of the cells on the exterior face while the oldest
cells press toward the center. The most important works concerning
the anatomy of the other tissues of the Loganiaceae, as well as an
account of his own researches in the same family, are well set forth in
the writings of Solereder *, who examined in detail the structures of
the different organs of representative plants of this family.
The anatomy of a number of species of Spigelia has been pre-
sented recently by Morelle *. He has considered the genus in five sub-
divisions, following Progel “, and gives detailed accounts of the
anatomy of eighteen species. Two of the species described, Spigelia
marilandica and S. anthelmia, are of especial interest. In the observa-
tions on the former, however, undue emphasis has been laid on the
so-called lateral wings of the stem. Commonly these are quite in-
conspicuous and occur prominently only in the vicinity of the leaf
bases. The term “somewhat four-angled” better describes the usual
condition of the stem. His figure showing the medulla of the stem
gives an incorrect idea of the structure, the attempt to represent a
resorbed condition of the pith having resulted in the appearance of
large air spaces between plates of spongy parenchyma. The paren-
chymatous cortex is likewise normally much thicker than he has
represented it, and he has not mentioned the occurrence of starch in
the cortex and pith of the rhizome and in the cortex of the root, a
very characteristic feature of S. marilandica.
With the exception of the wood his figure of the stem of Spigelia
anthelmia closely resembles the structures usually occurring in the
stem of S. marilandica.
1 Perrot. Le Tissue Criblé. These Agrég. École Pharmacie, pp. 161–173.
Paris, 1899.
... * Solereder, H. Ueber, systematischen Werth der. Holzstructur. Inaug. Diss.
§hen, 1885; Systematische Anatomie der Dicotyledonen, p. 696, Stuttgart,
8 Morelle, E. Histologie comparée des Gelsemiées et Spigéliées, pp. 50–95.
These, Paris, 1904.
4 Progel, in Martius's Flora Brasil, vol. 6, p. 248, 1868.
16 PINKROOT AND ITs SUBSTITUTIONs.
Summing up the general characters of the genus, Morelle finds
the stem possessing a peridem only in the perennial species. Some-
times the cortex includes large isolated sclerenchyma cells; some-
times it is wholly transformed into palisade parenchyma except at
the angles of the stem where it is sclerified. The pericycle is fre-
quently heterogeneous and thick, composed of fibers oval in cross sec-
tion and slightly lignified intermingled with parenchymatous cells.
The phloem is always very narrow, forming a continuous band. The
woody portion is more or less thick. The medullary rays with rare
exception have but one row of sclerified cells. Morelle finds that the
pith is usually resorbed, sometimes persistent, and inclosing large
isolated sclerenchymatous cells. The root structure is simple and the
cortex abundant and starch-bearing. The center is occupied by the
large woody portion, which is entirely lignified and contains numer-
ous vessels.
The histological characters of Spigelia longiflora Mart. have been
given by Cordero + and accord very closely with those worked out for
other species. He notes that in the rhizome the medullary rays can
not be distinguished, and states that the endodermis consists of two
rows of regular cells, a point worthy of note since in all the other
species of Spigelia in which the endodermis has been described it has
consisted of one row of cells.
CoNFUSED STATE OF KNOWLEDGE REGARDING PINKROOT.
The literature of pinkroot is sufficiently extensive and the experi-
ments and observations upon it numerous enough to have established
a considerable fund of accurate and definite knowledge concerning the
nature and activity of the drug. Nevertheless, very little is actually
known. Widely divergent opinions of its physiological properties are
extant, the variability in results attending its use is unexplained,
clinical observations are difficult to harmonize, the possession of poi-
Sonous properties is an open question, and wide divergence and non-
agreement exists among those who have studied the plant chemically.
The recognition of an adulterant which frequently totally re-
places the true pinkroot would naturally cause it to be prescribed with
reluctance, since the administrations of preparations composed wholly
1 Cordero, M. Datos para la Materia. Medica, Mexicana, part 1, p. 251, 1894.
IHISTORY. 17
or in part of the false pinkroot, the properties of which were un-
Known, might be followed by serious and unexpected results.
As will be shown later in this paper, studies purporting to have
been made upon the structure and the chemistry of Spigelia have in
reality been based upon some other plant mistaken for it. A striking
example of the manner in which these errors are propagated is af-
forded by Schneider’s work on powdered drugs". As characteristic
structures of Spigelia he describes and figures collenchyma cells,
Sclerenchyma cells, and cystoliths, and in his analytical key separates
Spigelia by its lack of starch 1 Now the presence of starch is a pro-
minent feature in Spigelia, while the structures just mentioned can
not be found in Spigelia marilandica, but are characteristic of Ruellia.
Because of the failure of those who have made clinical observa-
tions on the effect of the pinkroot to determine absolutely the identity
of their material, the question arises as to the validity of these observa-
tions, and it is not improbable that the properties ascribed to Spigelia
may not be possessed by this plant but belong rather io the adulterant.
18 PIN KROOT AND ITS SUBSTITUTIONs.
THE TRUE PINKROOT.
(Spigelia marilandica L., Syst. Veg. 197.)
SYNONYMS.
Spigelia oppositifolia Stokes, Bot. Mat. Med. I, 309.
Spigelia americana Monro., Med. Pharm. Chym. III, 270.
Lonicera marilandica Linn., Sp. Pl., Ed. 3, 249.
Periclymeni virginiana Raii., Dend. 32.
Spigelia lonicera Mill., Dict. W. 2.
Gentiana forte? quae Periclymeni, Catesby, Carol. II, 78, t. 78.
Anthelmia, Lining, Ess. and Obs. Phys. and Lit., I, III.
COMMON NAMES.
The common names under which Spigelia marilandica I. is
known are numerous, and may refer to the vivid appearance of the
plant, as pinkroot, starbloom, or to the locality and appearance com-
bined, as Carolina pink, Carolina pinkroot, Maryland pinkroot,
Georgia pinkroot, common pinkroot. Its medicinal use is indicated
in the terms wormgrass, perenniel wormgrass, wormweed, wormroot,
or American wormroot, wormseed, Maryland wormgrass. The use of
it by the Indians accounts for such malmes as Indian pink, India pink,
Indian plant, Indian pinkroot, and “unsteetla,” a name used by the
Cherokee Indians. It is also designated as Snakeroot (a name applied
to at least a dozen different plants, Lonicera, serpentine (La.), and
arapabaca. By German authors it is called Nordamerikanischer Spi-
gelie, Marylandisches Wurmkraut, Marylandische Spigelie, Gegen-
blatt spigelie, and Indianischer Pink. French writers frequently use
the names spigélie du Maryland, spigélie officinale, Oeillet de la Caro-
line, racine d’oeillet, and herbe des vers. Pinkroot is the name most
commonly used, and the term “true pinkroot” serves to distinguish
Spigelia marilandica (Fig. 1) from the plant widely substituted for
it and known as “East Tennessee pinkroot” (Fig. 2).
BOTANICAL DESCRIPTION.
This plant (Spigelia marilandica L.), belonging to the family
Logamiaceae, is an herbaceous perennial, which, springing up from a
wrinkled and knotty rootstock, attains a height of from six to eighteen
inches. The stem is erect and of a purplish color, obscurely four-
angled above, glabrous or nearly so, and simple or branched at the
base. The leaves are from two to four inches long, one-half to two
inches wide, entire, sessile, and ovate or ovate-lanceolate in shape.
1 Schneider, A. Powdered Vegetable Drugs, pp. 297—298, 1902.
SPIGELIA MARILANDICA. 19
They are of a rich dark-green color, membraneous, pinnately veined,
oppositely situated on the stem with their bases connected by a stipu-
lar line.
The flowers are large and showy and are borne in a solitary one-
sided terminal spike. The narrow tubular corolla gradually swelling
toward the middle is from one to two inches long, of a Scarlet color
outside, and is divided at the summit into five linear spreading lobes
which are yellow on the inside. The stamens are five, inserted on the
corolla. The anthers and the round slender style are exserted. The
two-celled capsule consists of two nearly equal and somewhat flattened
segments. The seeds are shield-shaped and few in number, ripening
in midsummer.
DISTRIBUTION AND HABITAT.
The area of country over which Spigelia marilandica is distri-
buted is quite large, but in much of the region its occurrence is not
more than occasional. It is said to grow in rich open woods and
copses from New Jersey to Wisconsin, Missouri, and Arkansas, south
to Florida and the Gulf to Texas. North of Virginia the plant is
rarely found. It is not mentioned in recent floras of New Jersey and
Pennsylvania, and three localities only are known in Ohio, one in
Indiana, and several in southern Illinois. In the Southern States,
aside from North Carolina where it is not a common plant though to
be found in the low and middle districts of the State, Spigelia occurs
scattered through the rich valleys and prairies from the Atlantic to
Texas. It is abundant in Tennessee, Georgia, South Carolina, Ala-
bama, and Louisiana, and from localities in these and other Southern
States the largest collections for drug purposes are made.
The plant is hardy and has been successfully cultivated in Eng-
land as well as in the United States. It grows best in a moist boggy
or peaty soil and does well usually in situations favorable for the
members of the Heath family.
DESCRIPTION OF RHIzoME AND Roots.
The rhizome of Spigelia marilandica (Fig. 3) is horizontal,
sometimes bent and becoming erect, from one-half to two inches long,
somewhat thicker than broad, knotty and wrinkled, dark purplish-
brown in color. The frequent branches are short and knob-like. On
the upper side are numerous cup-shaped scars where the former an-
nual stems have broken away, and from the lower side spring many
thin light-colored roots. Material collected in late summer or autumn
shows the buds for the next year’s stems. These are from one-fourth
to one inch long, scaly, and of a deep brownish-purple color. In the
dry condition the rhizome breaks readily, is hollow when the pith is
reabsorbed, and shows an oval cross section. The fractured surface
shows an outer ring of a dull-white color, within which is a ring of
20 PINKROOT AND ITS SUBSTITUTIONS.
yellowish wood. When the pith is present it is of a dull-white color
and is usually full of starch. *
. The roots are fibrous, branching, and brownish-yellow in color.
They are very brittle when dry, the broken surface showing a central
§
Fig. 3. Rhizome and roots of Spigelia marilandica L.
This figure shows the commercial appearance. The root system is often much more
fibrous and branching.
wood of light-yellow color, surrounded by a ring of dull-white tissue
loaded with starch.

SPIGELIA MARILANDICA. 21
The odor of the drug is slightly aromatic, the taste mildly bitter
and pungent. These properties vary, however, with the situation in
which it is grown and the time of gathering.
ANATOMY.
The material upon which the study of the anatomy was largely
based was obtained from plants of Spigelia marilandica secured from
Mr. S. O. Barnes, of Bridgeport, Ala., in
May, 1902, and kept under observation
on the experiment drug farm of the De-
partment of Agriculture on the Potomac
Flats at Washington, D. C., until flower-
ing established their identity beyond
doubt. All essential details of structure
have been verified in specimens from the
United States National Herbarium and
from a wide range of commercial samples
of pinkroot after careful microscopical
examination had demonstrated that they
were composed of authentic material.
The sections here described and figured
were cut from fully mature plants after
flowering, those of the stem from its
lower portion midway between nodes, .
those of the root about 2 cm. from its
attachment to the rhizome.
Anatomy of the stem. In the young Rig. 4. Cross section of the
stem there is a normal ring of bi- stem of Spigelia marilan-
collateral leaf-trace bundles which deve- died 11.
lop laterally until in the mature plant a mºto...". cº
perfect ring of xylem is formed. The º"iſº"; "ináriº
center of the stele is occupied by a pith ºi, º venes;
which is composed of large, thick-walled
parenchyma cells hexagonal in cross Séction and measuring from
30 (1 to 75 in diameter. Around the pith and limited by the xylem
is a layer of internal phloem in which sieve cells and companion cells
may be distinguished in longitudinal sections. In cross section
(Fig. 4) they can rarely be observed. Ilarge spiral vessels appear as

22 PINK10OT AND ITS SUBSTITUTIONs.
projections toward the pith on the inner portion of the xylem ring;
the remaining xylem consists of pitted cells 10 0 to 30 m in diameter
and 90 (1 to 165 ſº long. Around the xylem ring is a few-celled layer
of cambium, which is in turn surrounded by the external phloem, in
which sieve cells and companion cells may be clearly distinguished.
In the outer Zone of phloem occur large, relatively thin-walled
bast fibers, elliptical in cross section and from 15 p to 25 p in diameter
along the longer axis. The cortex is composed of large, relatively
thick-walled parenchymatous cells elliptical in cross section, measur-
ing from 20 p to 50 g in diameter and from 70 p to 155 m in length.
Between these cells occur large irregular intercellulars.
The epidermal cells very much resemble in cross section the cells
of the cortex, but they are somewhat smaller. The length of the epi-
dermal cells is approximately the same as the diameter in cross Sec-
|H-
[]
H
HHH
Fig. 5. Longitudinal section of the stem of Spigelia marilandica L.
Letters signify as in fig. 4. X 150.
s
|
#
:
º
º
ºº
§
#
s
ſº
[]
s\-Aºx-ºt[]
U
:
#
º
§
f
s
|
|
§
&#ăSºº
tion, the cells being nearly uniaxial. In longitudinal section (Fig. 5)
usually four epidermal cells are in contact with a single cortex cell
along its major axis.
Anatomy of the rhizome. The rhizome has a large central pith
composed of parenchyma cells smaller in size and of less regular out-
line in cross section (Fig. 6) than those in the pith of the stem and
the root. These cells are from 15 ºn to 35 g in diameter and from
30 p to 90 p long in the axis parallel to that of the rhizome. All the
pith cells are loaded with starch grains.
The fibrovascular bundles are of the bicollateral type similar to
those of the stem. There is present an internal phloem which occurs
as a several-celled layer between the pith parenchyma and the wood.
The xylem has a few spiral vessels on the side toward the pith, the

















SPIGELIA MARILANDICA. 23
- are devoid of starch content.
remaining tissue being composed of pitted cells 15 p to 25 (, in dia-
meter and from 75 ſº to 135 (1 in length. Lying without the xylem is
a few-celled layer of cambium, beyond
which is the external phloem, limited
by a layer of cells, in appearance some-
what differentiated from the adjacent
tissue, but not forming a distinct peri-
cycle, The walls of these cells show
but a slight thickening and the cells
In the endodermis the characteristic
thickening where the cell walls are in
contact is evident even in young mate-
rial in both cross and longitudinal sec-
tions (Figs. 6 and 7). These cells are
more elliptical than those of the cor-
tex, being compressed along the radial
axis. No starch is present.
The large parenchyma cells of the
cortex are irregular in size and con-
form to the prismatic type. Inter-
cellulars occur throughout the cortex,
but only sparingly in the outer layers.
The radial axis of the cells is common-
ly the shortest. All the cells of the
cortex are usually rich in starch. The
cells of the epidermis are uniaxial and
uniformly smaller than those of the
cortex. They are devoid of starch and
are thickened on the outer wall.
Anatomy of the root. The study of
the root structures here described was
made upon specimens from mature Fig. º.º.º sectiºn.9.hiáome
tº of Spigelin marilandica L.
plants in the second year of growth a, epidermis; b, cortex; d, xylem :
taken just after the close of the flower- % º'"...is º:
ing season. The larger roots had a * * * *
maximum diameter of approximately 2 mm. and exhibited all the
gradations in size usual in roots of fibrous type.

24 l’INKROOT AND ITS SUBSTITUTIONS.
The epidermis consists of a single layer of nearly uniaxial cells
with a thickened outside wall resembling a cuticle, sometimes staining
as intensely as the xylem. The diameter ranges from 25 ºn to 36 (1,
varying in different cells and with different axes in the same cell.
*S.
:
sº
R-
$
§
*.
#
§
º
§S
|
§§
§:
§
º
s
s
:
sN§
G.
;
:
§
º;
-Cl.
:#;º
s
;:-
º
:
>-
;3.
º#º
|
º
&
|
:
i§
##º
Fº
§
s
|
|
|m
;;- Fºr
º#:§§
§
-;
s§
§§
P
|
*
§:
º
º
SS
'S
*S
SO
*~
Fig. 7. Longitudinal section of rhizome of Spigelia marilandica L.
The rhizome here figured was not the same as the one shown in fig. 4. a, epidermis;
, cortex; d, xylem ; e, cambium; f, external phloem; g, internal phloem: h, spiral
vessel ; i, pith; j, endodermis : k, starch. X 15().
Many of the cells exhibit a nucleated protoplasmic content which
stains inténsely. No starch grains were observed in the epidermal cells.
The cortex consists of large parenchymatous cells, 30 m to 70 g.
in diameter, and from 110 !, to 140 m long. In longitudinal section
TV | | §§
| | §
| |#
| §
§ SeS
w t §§§ §§§
N D ſsº §
| "s S is H \# **ś
Fig. 8. Longitudinal section of root of Spigelia marilandica L.
d, xylem ; e, cambium : i, pith: j, endodermls; 1, pericycle. X 150,
-
s
§
**
a, epidermis; b, cortex;
(Fig. 8) from four to eight epidermal cells are in contact with one
cortex cell. The long axis of these cells is parallel to the axis of the
root. In the outer layers the cell walls are closely applied, the cells




SPIGELLA MARILANDICA. $
25
being therefore regularly hexagonal in cross section; in the inner
cortical layers the cells are not closely compacted, are elliptical in
cross section (Fig. 9), and show large intercellular spaces. The proto-
plasmic contents stain less intensely than QCCD
in the case of the epidermal cells. Numer- JOY <!
& Y-CDU-
ous starch grains appear in nearly all the & Sº -
cortical cells. * *—s. CO
Lying within the primary cell layer of Jº ^
the cortex is the endodermis, consisting sº
of cells somewhat smaller than those of O Y
the cortex and, so far as observed, devoid tº Fº A,
of starch grains. The pericycle consists
of a layer of cells of approximately the
four-sided prismatic form, the long axis
lying in the periphery of the section at
right angles to the axis of the root. These
cells measure 60 g to 90 p along the
longer axis and 45 g to 75 ( along the
shorter axis. Within this and entirely
surrounding the xylem is the cambium
layer.
The Nylem is composed of pitted,
tracheae 15 (, to 30 tº in diameter and
112 tº to 210 (, long. This is the only
type of wood element observed in the root
of Spigelia. Within the inclosing ring
formed by the xylem are the parenchyma
cells of the pith. In the oldest roots ex-
amined the center of the axis was almost
wholly composed of xylem tissue, and the Fig. 9. Cross section of root
of Spigelia marilandica I.
bith parenchyma is probably best re- a, epidermis ; b, cortex ; d.
Xylenn & e, cambium ; i, pith ;
garded as temporary only. A lºodermis; , periºscle.
Nº 1 50.
CHEMISTRY OF THE PLANT.
Of the numerous contributions made to the chemistry of Spigelia
marilandica L. that of Feneulle must be regarded as the first of im-
portance, since, the view is now generally accepted that he really

26 PIN KROOT AND ITS SUBSTITUTIONS.
worked with this plant and not with Spigelia anthelmia L. as he sup-
posed. In 1823 Feneulle *, a chemist and druggist of Cambria, made
an extended qualitative examination of the chemistry of the plant
which he held to be Spigelia anthelmia L. and published his results
as follows:
The powdered root was treated with sulphuric ether until solu-
tion was effected, when the solution was of a lemon-yellow color, and
turned litmus red. This was reduced to one-sixth of its volume by
distillation, and the liquid remaining in the retort was left to eva-
porate spontaneously. The ethereal distillate did not contract any
odor and was not acid. The residue was strongly acid and on diluting
with distilled water a soft, fat, unctuous substance separated, of acid
taste and accompanied with a little resin. The aqueous solution pre-
cipitated salts of iron peroxid black, and contained gallic acid with a
bitter substance. º
A second portion of the root treated with ether was boiled and
treated with pure alcohol. When filtered it deposited nothing, and
on distillation left a residue formed of resin, a greenish oil, and a
little acid and bitter substance.
A third portion of the root, macerated in distilled water, filtered,
and boiled, formed a coagulum which burned like animal matter and
was soluble in potash,_albumin. On distillation the remainder gave
an aromatic product not affecting litmus but clouding lead acetate
and silver nitrate. The decoction remaining in the retort when filtered
was transparent, brown in color, bitter, and astringent. With ace-
tate of lead it gave a yellowish white precipitate, which on purification
yielded acid malates of lime and potassium. The decoction when
freed from the precipitate of lead by hydrogen sulphid, filtered, eva-
porated, and treated with alcohol left a colored substance of sweetish
taste and soluble in water, while the alcohol took up a bitter brownish
matter, apparently the active principle. The constituents may be
summarized thus: A fatty oil : a volatile oil; resin, small quantity;
bitter substance; muco-saccharin matter; gallic acid; albumin;
malates of lime, potash, etc.; lignin.
Three years later Wackenroder * made Spigelia marilandica the
subject of chemical research. He carefully states that the confusion
1 Feneulle, H. Analyse (le la §le Anthelminthique. Journal de l'harmacie
97. tº &
et des Sciences Accessoires, 9: * & P s & ſº a n & &
2 Wackenroder, H. G. F. De Anthelminthicis, p. 52, Göttingen, 1826.
SPIGELLA MARILANDICA. 27
between this species and Spigelia anthelmia may be avoided by noting
that the latter has annual roots. In his analysis he used the entire
plant, investigating the roots as well as the stem and leaves. His re-
sults are as follows:
Stem and leaves:
Resin, chlorophyll . . . . . . . . . . . . . . . . . . . . . . . . . . 2.40
Myricin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30
Resin (special) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50
Tannin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.20
Lignin . . . . . . e e s e e s e e s is nº e º 'º e s s m e º e º e º e º e s s 75.20
Malate of potassium and KCl . . . . . . . . . . . . . . . . 2.10
Malate of lime . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.20
Root:
Bitter resin and fatty oil . . . . . . . . . . . . . . . . . . . 3.13
Tannin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.50
Extractive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.84
Lignin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.69
The next to study this plant chemically was Stabler", who
studied the root of Spigelia, but whose work was qualitative only and
undertaken to determine, if possible, the seat of the active principle
and the nature of the volatile oil to which the odor of the root is be-
lieved to be due. His analysis gave as constituents of the rhizome and
roots a bitter, uncrystallizable principle to which the activity was
ascribed, a small quantity of volatile oil, tannic acid, inert extractive,
wax, resin, and salts of potassium, sodium, and lime. The active
principle is acrid and bitter, soluble in water and alcohol insoluble in
ether, decomposing on volatilization, neutral and deliquescent.
In 1879 Dudley 4 was led to suspect the presence in Spigelia of
a volatile alkaloid, since the activity is reputed to become somewhat
diminished in the old roots. He submitted the root of the drug to
distillation with milk of lime over a paraffin bath, received the distil-
late in hydrochloric acid and evaporated it to dryness over a water
bath, and purified it by extraction with absolute alcohol. The alco-
holic filtrate when evaporated yielded a crystalline substance which
was water soluble. In solution this substance gave with iodin-potas-
sium-iodid a brownish-red precipitate, with metatungstic acid a white
1 stabler, R. H. () n Spiurelia, Proc. Aumer, Pharm. Assoc., 6: 132–134, 1857.
2 Dudley, W. L., . Preliminary Notice of a New Volatile Alkaloid. A uner. Chem.
Jour., 1 : 1 54—l 55, 1879–80. * # * * *
28 PINKROOT AND ITS SUBSTITUTIONs.
flocculent precipitate, and with potassio-mercuric iodid a white crys-
talline precipitate. This latter reaction seems to distinguish it from
the other volatile alkaloids with which it was compared, as nicotine
and lobeline, which gave a yellow precipitate. As a result of this
work the name spigeline was assigned to the new volatile base whose
presence was indicated. sº
A comparative analysis of the true pinkroot was made by Boyn-
ton in 1884 with a view to furnishing data for distinguishing it
from the Carolina phlox which was supposed to be substituted for it.
His results were very general and can be regarded only as a proximate
analysis, since he found neither the active principle nor the volatile
oil which previous workers had demonstrated. According to his pub-
lished statement the analysis gave the following as constituents of
Spigelia marilandica :
Moisture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.621
Benzol extract (resin, wax, fat) . . . . . . . . . . . . . .518
Alcohol extract (resin, tannin, extractive). ... 7418
Water extract (gum, tannin, extractive) . . . . . . 11.008
Ash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.500
These accounts on comparison are seen to be indefinite and con-
tradictory, and beyond the statement that the plant contains resin,
starch, and tannin, little can be said. A careful and thoroughgoing
analysis is needed to determine its actual constituents.
MEDICINAL PROPERTIES.
The chief characteristic of spigelia, and the one which first at-
tracted favorable notice, is its action as a vermifuge, and it has long
been recommended as a powerful anthelmintic. Chalmers, Garden,
and Lining, who first introduced spigelia to the medical profession,
regarded it as the best remedy for the very prevalent worm disorders
of their time. These authors cite several instances from their private
practice in which desperate cases of worms were cured by the ad-
ministration of pinkroot.
A number of authors claim for spigelia narcotic properties.
Lindley* observed that its use was occasionally accompanied with
1 Boynton, W. C. Laboratory Notes. Amer. Jour. Pharm., 56: 570, 1884.
2 Lindley, J. Introduction to the Natural System of Botany, p. 216, 1831,
SPIGELLA MARILANDICA. 2%)
violent narcotic effects. Eberle found that a strong decoction of the
root showed narcotic properties and produced in a child symptoms
similar to those caused by stramonium seed, and Bigelow * states that
it is narcotic in large quantities. Hale * found that spigelia in addi-
tion to being a powerful anthelmintic possessed narcotic and to some
extent cathartic properties. Spalsbury “observed that unusual symp-
toms attended the use of spigelia, the most important of which are
irregular pulse, strabismus of the eye, dilatation of the pupils, and
nervous tremors. .ºr
Other disagreeable and alarming symptoms frequently followed
the use of this drug, according to some practitioners. Chalmers",
who esteemed it as the best of vermifuges, reported that its use was
often attended with drowsiness, pain in the forehead and eyes, and
dimness of sight; in two cases convulsions supervened which ter-
minated in death. Garden" also observed a variable effect from the
use of this root and regarded large doses safer than small, as the latter
were more frequently followed by alarming symptoms of nervous dis-
turbance. Home ", on the other hand, performed a large number of
experiments with spigelia but observed none of the undesirable effects
attributed to its action, even though the drug was given in large
doses. Thompson * performed a number of experiments with a view
to determining more definitely the physiological properties of spigelia.
Large earthworms placed in a decoction of the root were quickly
stupefied and died after a few minutes, and doses of the powdered
root administered to a dog caused the death of a huge worm which
infested its digestive tract. From these and other similar results
Thompson inferred that spigelia possessed great anthelmintic proper-
ties. From a series of experiments upon himself and some of his
colleagues he learned that spigelia caused cardiac depression, and
therefore concluded that it might be useful as a febrifuge. He ob-
served no instance in which the drug had a tendency to produce con-
i Eberle, J. Materin Medica, and Therapeutics, vol. 1, p. 214, 183 1.
2 Bigelow, J. American Medical Botany. vol. 1, p. 142, 1817.
8 Hale, J. Report on Medical Botany of the State of Louisiana. New Orleans
Med. and Surg. Jour., 9 : 167, 1853.
* Spalsbury, G. W. . Unusual_Effects from the Use of the Spigelia marilandica.
Boston Med. and Surg. Jour., p. 72, April, 1855.
67. ºners. An Account of the Weather and Diseases at South Carolina, vol. 1,
p. 67, 1776.
6 Garden, A. An Account of the Indian Pink. Essays and Observations Phy-
sical and Literary, 3:146, 1771.
7 Home, F. Clinical Experiments, p. 420, 1780.
8 Thompson, H. F.Xperimental Dissertation on the Spigelia Marilandica or
Indian Pink. 1 SO2. w" e
30 PINKROOT AND ITS SUBSTITUTIONs.
vulsions, dimness of sight, or dilated pupil, and ascribed these symp-
toms when they occur to the disease itself, believing that they had
been wrongly mistaken for the operation of the drug on the system.
In contrast to the view of Garden and of Buchan * that the bad
effects of spigelia are due to its administration in Small doses,
|Bartholow * believed that moderate doses stimulated intestinal move-
ment and accelerated the action of the heart, and that large doses
caused vertigo, dim vision, dilated pupils, convulsions, etc. Dewees *
also thought that the evil effects were due to large doses or overdoses.
It is now generally held that a small dose produces little effect on the
system, that a moderate dose, though variable in action, may exert
cathartic action, and that a large dose or an overdose will produce the
disagreeable symptoms referred to above.
The physiological reaction of lower animals to spigelia was in-
vestigated, by Hare ‘, who found that it produced in them symptoms
of poisoning, including strabismus, dilatation of pupil, loss of spinal
motor power, and central inhibition of circulation followed by death
due to failure of respiration.
For many years the effects of pinkroot have been regarded as un-
doubtedly variable; sometimes its use has been attended with good
results, sometimes none at all. These unequal and uncertain results
have been believed to be due to the greater activity of the fresh plant,
which gradually diminished as the root dried out and aged. The evil
action of spigelia was ascribed almost wholly to the fresh root, and it
is said rarely to occur in the dry plant ". Hale" recommended the use
of the fresh root, since he believed that it deteriorated rapidly on
keeping, and Dudley 7 was led by the reputed lack of activity in old
roots to search for the volatile alkaloid which he claims to have
isolated from spigelia. Murray * attributed the absence of unpleasant
symptoms following the use of the plant in England to the fact that
it is used there only in the dried state. Under present methods of
Buchan, W. Domestic Medicine, p. 60S, 1825.
ed. 5. *ºsº. A Practical Treatise on Materia Medica and Therapeutics,
chndºis; A Treatise on the Physical and Medical Treatment of
News, #sºlºs. The physiological Action of Spigelia or Pink root. Medical
1821. Medical Botany or History of Plants in the Materia Medica, vol. 1, p. 31,
; Hºw.", Preliminary Notice of a new Volatile Alkaloid. Amer. Chem.
Jour, 1 : 154, 1879–80.
8 Murray, J. System of Materia, Medica and Pharmacy, p. 278, 1824.
RUELLIA CILIOSA. 31
preparation by far the largest part of the pinkroot becomes fully dried
before use, and may remain in the drug lofts several years before it is
worked up into its officinal preparations. This may account for the
fact that the comparative merits of fresh and dry roots have attracted
almost no attention for over thirty years.
The writers of fifty years ago paid considerable attention to the
poisonous action of spigelia. Bureau regards it as a narcotic poison
which in extreme cases can cause death. Brown prescribes a tincture
of pinkroot in worm mixtures, but cautions against the plant sold as
such by the druggists, much of which he says is poisonous. The only
statement of poisoning attributed to pinkroot observed in modern
literature is that of Free *, who records as recently at 1894 a case in
which a mixture of spigelia and Senna was administered, the death
which followed being attributed to the poisonous property of the
pinkroot. -
The bad effects that have been observed in the use of pinkroot
have been attributed to some other plant inadverently or fraudulently
collected and sold as spigelia *, while Ewell ", who recommends its use
as a febrifuge, also ascribes its deleterious action to admixture with
Some other root. Although the drug is now in general use in both
regular and domestic practice in the United States, little has been
heard in recent years of its undesirable action.
º
1_Bureau, L. E. De la Famille des Loganiacées. These Fac. Méd., Paris, pp.
132–14 5, 1856. sº
2 Brown, O. P. The Complete Herbalist, p. 195, 1867.
* Free, J. E. Pinkroot Poisoning. Med. and Surg. Reporter, 70 : 633, 1894.
* Kost, J. Elements of Materia Medica and Therapeutics, p. 356, 1858.
5 Ewell, J. The Medical Companion, ed. 5, p. 605, 1819.
32 PINKROOT AND ITS SUBSTITUTIONS.
EAST TENNESSEE PINKROOT.
DISCOVERY OF BOTANICAL SOURCE.
The presence on the market of a root extensively substituted for
spigelia has long been recognized, and it has been widely commented
on by writers on medicinal plants, to whom, however, the botanical
source was unknown.
For some time this subject had received the attention of Dr.
Rodney H. True and he demonstrated several years since to his own
satisfaction that an unsuspected substitute had crept into the market
and to a considerable degree had replaced the true article. It was
shown in 1900, by Mr. S. J. Poole, a student of botany at Harvard
University working under Dr. True's direction, that the substitute
belonged to the genus Ruellia of the family Acanthaceae. The sig-
nificance of this substitution with reference to the commercial and
medical status of pinkroot was pointed out.
In directing the experiments of the office of Drug Plant Inves-
tigations of the Bureau of Plant Industry, Dr. R. H. True", in 1903,
with the purpose of learning something more definite concerning
pinkroot, ordered from a dealer in eastern Tennessee plants of Spi-
gelia marilandica for cultivation at Washington, D. C. The plants
received when the order was filled had slender, hairy stems and ellip-
tical, hairy leaves. They were placed under close observation and
upon flowering were positively identified as Ruellia ciliosa Pursh
(Fig. 2).
The significance of this discovery can best be appreciated when
it is remembered that there exists a widespread confusion concerning
this plant. According to some authors whose statements have been
unquestioned for years this false pinkroot was the Carolina phlox
(Phloa ovala L.). Others have examined the rhizome and root micro-
scopically and chemically while under the impression that they were
dealing with spigelia. Clinical observations on the action of Spigelia
have been recorded which are not free from the suspicion that they
belong in reality to Ruellia. These errors also appear in the latest
text-books, dispensatories, and materia medicas, and are being Con-
tinually multiplied and distributed throughout the literature of the
subject.
MORPHOLOGICAI, CITARACTERS.
East Tennessee pinkroot (Ruellia ciliosa Pursh) is a member of
the family Acanthaceae, which comprises about 175 genera widely
distributed in temperate and tropical regions.
1 True, R. H. Pharm. Tºev., 21 : 364, 1903.
RUELLIA (II,IOSA. 33
This plant, growing in dry soil in woods and thickets, is an
herbaceous perennial with an erect stem which frequently sends out
lateral branches. The stems and leaves are markedly hairy, a char-
acter which is less pronounced in Ruellia strepens L. and R. parvi-
flora (Nees) Britton. The leaves are opposite, sessile and very short
petioled, oblong or oval, with margins entire or rarely dentate. The
rather large and showy flowers are borne in the axils of the leaves and
may be single or clustered. The bluish-purple corolla has a straight
or more or less curved tube, abruptly dilated above, terminating in a
border with five obtuse lobes. The four stamens are borne on the
corolla and are nearly equal in length or didynamous. The filaments
are enlarged toward the base and are united two by two in a variable
degree. The fruit is a two-valved capsule containing six to many seeds.
The rhizome (Fig. 10) is short and erect and has a small central
Fig. 10 Rhizome and roots of Ruellia ciliosa I’ursh.
At a, a is shown the tough yellow wood left on the breaking a way of the
readily removable bark.
pith and thick, hard wood. The roots are coarse and straight, some-
times wiry in appearance, the color varying from yellowish-brown to
dark-brown. The roots are usually uniform in diameter throughout
the greater portion of their length, giving off but very few small and
fibrous branches. The bark of the roots is readily removable and
frequently breaks off in handling, leaving the tough, wiry, straw-
colored wood.
Of the three species of Ruellia mentioned above, R. ciliosa Pursh
has the widest range in the United States. It occurs from New Jersey
to Florida, Michigan, Kansas, and Louisiana. The flowering season

34 PIN KROOT AND ITS SUBSTITUTIONS.
is from June to September. 12. slrepens usually flowers earlier and
generally occurs in about the same situation and range as R. ciliosa.
R. parviflora, or southern Ruellia, occurs commonly in the United
States south of Maryland and West Virginia and as far west as
Texas.
ANATOMY.
The general facts concerning the anatomy of the Acanthaceae
are summarized by Solereder *, who makes very prominent, especially
as a character in classification, the occurrence of cystoliths, a struct-
ure characteristic of numerous genera of this family, including
Ruellia.
Dethan * studied several species of Ruellia and gives an account
of the anatomical structure of Ruellia patula Jacq. and R. luberosa
II., neither of which, however, is known to occur in the range of
R. ciliosa Pursh.
The material used in this study was obtained from the plants
under cultivation on the experimental drug farm at Washington.
III order to widen the field of observa-
tion, as well as to obtain some idea of the
extent of the occurrence of Ruellia as pink-
root, a large number of commercial samples
were examined and compared with authentic
material. Fully 50 per cent. of these samples
consisted wholly of Ruellia, and many of
the remainder contained Ruellia in varying
§ g; though usually large quantities.
º V. Anatomy of tle stem. The aerial stem
KY of Ruellia is distinctly four-angled, and is
almost square in cross section (Fig. 11).
The pith is composed of regular, elliptical,
Fig. 11. Cross section of thick-walled parenchymatous cells between
. º *" which large intercellulars occur. The pith
... epidemi, b, paren cells as well as those of the cortex are devoid
*}” sº, º of starch. A layer of internal phloem sur-
ºluºi, º, ºnal phlºem, rounds the pith. The layer is thickest at the
h, spiral vessel; i, pith; j,
endödermis; m, cystoliths; angles of the stems, where there is also a
n, collenchymato (1s layer of
the cortex. × 150. greater development of the mechanical tissue.
à
;
§
§
§§§ º
§
§
º
º
º
: Brittoº, N.L. Manual of the Flora of the United States and Canada, 1901,
* Solereder, H. Systematische Anatomie der Diéotyledomen, p. 696, 1899.
* Dethan, G. Des Acanthacées Médicinales, p. 81–86, 1896. " . .

RUELLIA CILIOSA. 35
The xylem is disposed in a woody ring which follows closely the
general shape of the stem. It is thickest at the angles of the stem,
where also the vessels are largest and most numerous. In the inner
portions of the xylem spiral vessels occur, some large with a close
spiral, some small with a loose spiral. Large annular vessels and
wood cells with simple pits make up the remaining xylem.
Outside the wood and entirely surrounding it is a narrow few-
celled layer of cambium. The external phloem is limited exteriorly
by a thick pericycle, in which occur numerous long fibers, elliptical in
cross Section and having a relatively large lumen. The cells of the
endodermis are large and show the characteristic cuticularization in
their lateral walls. The endodermis is readily recognized, though its
cells differ little in size and general appearance from those of the
cortex.
In the stem, as well as in the root and rhizome of Ruellia, the
cortex is differentiated into an outer collenchymatous layer and an
inner portion of large, relatively thin-walled, elliptical parenchyma-
tous cells. Cystoliths and sclereids are absent from the inner portion
of the cortex; in which large intercellulars occur. Starch is absent
from the cells. The outer portion of the cortex, comprising six to
eight layers of cells, is composed of collenchymatous cells of about
half the diameter of the inner cortical cells. Cystoliths and sclereids
are absent here as well as in the inner layers.
The epidermis consists of a single layer of cells elliptical in cross
section (Fig. 11) and larger than those of collenchyma. The outer
walls are thickened, and usually give a satisfactory cutin reaction.
In longitudinal section (Fig. 12) the cells are several times longer
than in cross section. Num-
erous cystoliths occur in
the epidermis. While the
cells containing cystoliths
may not strictly be termed
sub-epidermic, they are
larger than the other epi-
dermal cells and appear to
push down into the cortex
as though an increase in
size had occurred in the *...º.º. " "
cystolith-bearing cells after Iletters signify as in Fig, 11 , X 150.
\
-
2
º
-
º

36 PINKROOT AND ITS SUBSTITUTIONs.
the epidermis had fully formed. The surface of the stem is thickly
set with epidermal hairs which arise as extensions of the epidermal
cells. These are of two kinds, multicellular gland hairs, and simple,
pluricellular, non-glandular hairs, the latter being curved and having
the apex uniformly directed toward the base of the plant.
F-F-asſ=E===ff" In longitudinal section the cysto-
tº: liths are fusiform or conical and
occupy the larger epidermal cells.
In life the cells not bearing cysto-
liths contain a coloring matter
which imparts the purplish color
characteristic of the stem.
Anatomy of rhizome. The struc-
ture of the rhizome differs in
several important particulars from
that of the stem. The relatively
small pith is composed of large,
thick-walled parenchyma cells de-
void of starch grains. The peri-
medullary sieve tissue is absent in
rº te º
C the mature rhizome. The wood is
º sº thick C d of simple pitted
ºś § lick, composed OT Slmple pitte
§§ # Bº cells and vessels. Large vessels oc-
tº: cur between the somewhat indis-
§§§ Eğ e
º tinct medullary rays. The few to
§ºğ §§D . e
ºº d’ several celled cambium layer is
) §§ C § {} tº º g & •'
º limited by the pericycle, in which
W \) o #º 㺠O tº
†º occur a few thickened sclerenchyma
jičğ #º O tº tº ſº *
sº § ſibers. The endodermis is distinct
Tiš * © tº
Öğ and cleally shows the characteristic
º §§ jº lateral thickenings
2$ᚊ §§ §§ {} Ó ſº C C 8 - -
§§§ {\_lſ. º § § * º & º
ºf The cortex, like the stem, is dif-
Öğ3 §S); ºft|U}} ſº e
º § ferentiated into an outer and an
\ & Pºe D ſ re º
ºx) ºrs inner Zone. The latter consists of
Fig. 13. Cross section of rhizome large parenchymatous cells, ellip-
of Ruellia Giliosa Pursh. tical in cross section (Fig. 13) and
a, epidermis; b, cortex ; c. bast * tº gº e *
fiber; d, xylem ; e, Ca In bill n : i, pith ; displays lar ge inter cellular spaces.
j. endodermi ; 1, perieycle; m, cysto- * e {
lith ; In, collenchyma ; O, sclerid. X 150. Fl equent scleroids of &l. yellow color

RUELLIA CILIOSA. 37
occur in this Zone. They are strongly lignified, oval in cross section,
and show the characteristic concentric markings. In longitudinal
Sections (Fig. 14) they are nearly rectangular and show numerous
pore canals. The outer zone consists of collenchymatous cells much
smaller than those of the inner cortex, and exhibits numerous cysto-
liths. They are very similar to those occurring in the stem. A few-
celled corky layer is present in mature plants. The epidermal cells
are thickened on the external wall.
Anatomy of root. The mature root of Ruellia has a central cylin-
der of the pentarch type, surrounded successively by phloem, peri-
cycle, and endodermis. In young roots, the pith cells are thin-walled
|
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§
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§
º
§
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i
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º
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º º º * *
• ~ *
tº * * *
º - Sł.
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. . . **º -
tº wº º -
º: s &
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*:W Sºlº º
º { §§SN
º: º * * * wº
& © Sº tº.
*: |S$ *
º -> *
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- - : bºº º
#!!! Sº Nºsſº
ºff, & N. - § ºl% º
º: * w C *
$ff § - :**** Rº
º | ES:Sºs - º ** wº
§ ºs º SSSSR's ºrº e tº º
wº -
º SS$ ºt. *
sº * º * wº
º vº º º * ºws
º $3 Sºº's & e *
S$º º *
~ e
SSº RS:
- *** - w * * *** *
& º º *
Pº 3.x: §§§§ * §§§
* * º * º e tº º *
* tº sº tº º
§§§ §§§
&
Fig. 14. Longitudinal section of rhizome of Ruellia ciliosa Pursh.
º
* a sº
*
**
Sº
º
sºlº ºs
** § * * *
Sºssºws sºlº - a
a, epidermis; b, parenchymatous, cortex; e, bast fiber; d, xylem ; e, , cambium ; i, pith:
m, cystolith; n, collenchymato is layer of cortex ; o, sclereid. XI 50.
and parenchymatous, but in the mature condition these cells are
strongly thickened and give an intense lignin reaction with phloro-
glucin and hydrochloric acid.
The xylem cells are in general hexagonal in cross section (Fig.
15); the thickened walls are marked by simple elliptical or slit-like
pits. The phloem which surrounds the xylem has thin-walled cells
of irregular cross section. In the outer layers occur groups of bast
fibers, usually five in number, between which the medullary rays ex-
tend, marking the individual bundles forming the stele. These fibers
are from 0.3 to 1.5 mm. in length, elliptical in cross section, and show
a small central lumen. The pericycle appears as a layer of thin-
















38 PINKROOT AND ITS SUBSTITUTIONS.
walled parenchyma cells of regular oval outline, limited externally by
the chdodermis, which is here a ring of elliptical cells with dark walls
Somewhat thicker than those of the adjacent tissue.
The thick cortex surrounding the stele shows, as in stem and
rhizome, a differentiation into two zones. The three to five celled
outer layer consists of collenchymatous cells in which occasional cys-
toliths occur. The inner layer is made
up of thick-walled parenchymatous
cells, frequently inclosing cystoliths
㺠and numerous sclerenchymatous cells
㺠which give the characteristic reactions
4; SOO}+\">''2'S, for lignified tissue. The cells of the
Outer cortical layer are much smaller
than those of the inner layer.
The cystoliths characteristic of this
plant occur abundantly in the cortical
cells. In cross section they are circu-
lar or elliptical, and show a series of
concentric stratifications. Portions of
the surface of cystoliths are produced
into tooth-like projections. In longi-
tudinal section (Fig. 16) they appear
rounded at the end which is attached,
and taper toward the lower extremity.
In the presence of hydrochloric acid
rapid effervescence occurs, due prob-
ably to calcium carbonate, which is
believed to be the chief constituent of
Pig. 15. Cross section of the cystoliths. The attachment is not evi-
root of Ithelia ciliosa Pursh, dent except in fresh material, in which
a, epidermis; b, cortex; c, bast g
fibers.ºxylem.j, endodermis; it was demonstrated at the large
I, pericycle; m, cystoliths: n, col-
lenchyma, ; 9, sclereids. X 150. rounded end.
A one to three celled corky layer
underlies the epidermis. The epidermis itself comprises a single
layer of cells with walls somewhat thickened. The surface of the
growing root is thickly beset with long, simple, unicellular hairs
which arise as modified epidermal cells.



RUELLIA CILIOSA. 39
CHEMISTRY OF THE PLANT.
Almost nothing is known of the chemistry of Ruellia. The mem-
bers of this genus which have medicinal properties are used almost
exclusively in tropical or subtropical countries and have not been
thoroughly studied. Such facts as are available concerning the con-
stitution of this plant were obtained by a chemist who believed he
was studying Phlow carolina, but, as will be shown, really used the
plant Ruellia in his investigations.
Trimble in 1886 reported an analysis of Phlow carolina in the
course of which he obtained by the solvent action of petroleum spirit
a red and fluorescent solution which upon evaporation deposited a
residue in the form of masses of fern-like crystals on the side of the
|
|
Fig. 16. Longitudinal section of Ruellia ciliosa Pursh.
a, epidermis; b, parenchymatous cortex ; c, bast fiber; d, xylem ; m, cystolith : n, col-
lenchymatous cortex: o, sclereid. X 150.
vessel, while in the bottom it formed into star-like circular masses of
acicular crystals. The dry residue was then treated with dilute alco-
hol to remove the red coloring matter, and further purified by crys-
tallizing first from boiling-hot 95 per cent. alcohol and then from
absolute alcohol. The compound obtained was soluble in chloroform
and ether, melted at 155.4° C., and burned with a smoky flame. In
view of its physical and chemical properties he decided that the com-
pound isolated belonged to the camphor group and suggested the
name “Phloxol.”
Two years later further studies on this compound were reported
1 Trimble, Henry. An Analysis of the Underground Portion of Phlox Carolina.
Amer. Jour. Pharm., 58: 47.4—481, 1886.

{() l’INKROOT AND ITS SUBSTITUTIONS.
by Abbot and Trimble ', and the results of its ultimate analyses
formed the basis for the theory that the compound was an unsatu-
rated hydrocarbon of the formula (Cai Has)x.
For the purpose of comparison Spigelia was similarly treated
with petroleum spirit, but no such compound as that obtained from
the supposed Phlox was obtained. This result suggested important
chemical differences between the two plants and led to Trimble’s pro-
position to use the presence of the so-called phloxol as a means of
distinguishing Spigelia from Phlox, a test which has been generally
accepted in pharmaceutical literature.
PIILOXOL A CONSTITUENT OF RUELLIA.
The discovery that Ruellia is the botanical source of the East
Tennessee pinkroot and the failure to find the Carolina phlox in any
adulterated samples of pinkroot examined, suggested the possibility
that the plant from which phloxol had been isolated was not Phlox
but a species of Ruellia. Accordingly an attempt was made to verify
the source of the phloxol by the duplication of that part of Trimble's
work on Phlox which dealt with the petroleum ether extract and the
compound isolated therefrom. Samples of the three plants Phloa.
ovala L. (Phloa carolina L.), Ruellia ciliosa Pursh and Spigelia
marilandica L. were taken from the testing gardens of the U. S. De-
partment of Agriculture where they were under cultivation, a condi-
tion which made possible the securing of authentic specimens of
each plant.
Each sample of this material was first reduced to a fine powder
by grinding and was then thoroughly exhausted with petroleum ether.
The solutions were then filtered into beakers and the appearance of
each observed. That from Spigelia remained clear and uncolored, the
one from Phlox had a yellowish tinge, probably due to chlorophyl dis-
solved from leaf fragments intermingled with the roots before grind-
ing, while the solution from Ruellia was red and fluorescent, as
described by Trimble for Phlox.
Upon evaporation the solution from Spigelia deposited a gummy
mass on the bottom of the beaker, throughout which occurred masses
1 Abbot, Helen, and Trimble, H. On the Occurrence of Solid Hydrocarbons in
I’lants. A mor. Jour. I’harm., (30: 3:21–324, 1888.
I’III.ox (AROUINA. 41
of small sphaero-crystals. The solution from Ruellia deposited fern-
like masses on the side of the beaker and on the bottom groups of
acicular crystals, similar to those reported as derived from Phlox.
After purification by recrystallizing from alcohol, the melting point
was found to lie between 153° and 155° C., results which agree very
closely with those given for phloxol ".
These experiments furnish good evidence for the following con-
clusions: (1) That Trimble did not have the Carolina phlox as he
supposed, but probably Ruellia; (2) that the so-called phloxol is not
a constituent of Phloa ovata, but in all probability occurs in Ruellia.
MEDICINAL PROPERTIES OF RUELLIA.
It is not possible at present to ascribe any specific medicinal
properties to Ruellia ciliosa, although several other members of the
genus have some well-recognized uses in certain maladies. Dethan *
has given an extended account of the useful Ruellias in his thesis on
the medicinal Acanthaceae. The value of his work, however, is
diminished by the careless and incorrect citation of his authorities.
Some of these inaccuracies are repeated by Bocquillon * in a very
recent work; hence only such statements of these two authors as could
be verified from original sources have been credited.
The roots of Ruellia tuberosa L., R. patula L., R. hispida Rich.,
and R. strepens L. are emetic and are used in America as a substitute
for ipecac *, the two former being similarly used in the Antilles ". In
Guiana and the Antilles R. tuberosa L. is employed in intermittent
fevers, whooping cough, puerperal peritonitis. etc." In the Barbados
the root has a great reputation among the natives as a cooling
diuretic ". In the East Indies the natives bruise the leaves of R.
strepens L., and mix them with castor oil, forming a valuable applica-
tion in cases of children’s eruption due to dentition *. R. repanda L.
is employed in the treatment of cases of angina and conjunctivitis. “
i Further studies on this conn pound are in progress in the laboratories of Drug-
º Investigations of the Bureau of Plant Industry U. S. Department of Agri-
Culture.
2 Dethan, G. Des Acanthacées Médicinales, pp. 80–86, Paris, 1896.
S Bocquillon-Limousin, H. Manuel des Plantes Médicinales, p. 244, I’aris, 1905.
4. Baillon, H. Histoire des Plantes, ! (): 4:21, 1894.
1st. Dechambre, A. Dictionnaire Encyclopédique des Sciences Médicales, 5 : 583,
é Corre and Lejanne. .Résumé de la Matière Médicale et Toxologique Coloniale,
p. 124, 1887.
1901. Freeman, W. G. Notes from Barbadloes. Pharm. Jour. and Trans., (57 : 61 5,
8 Ainslee, W, Materia Indica, vol. 2: p. 153, 1826.
42 l’INKROOT AND ITS SUBSTITUTIONS.
In the Antilles an infusion of the leaves of R. coccinea Vahl. is used
as a diuretic, and a sudorific preparation is made from the buds ';
here also R. clandestina L. serves for a ſebrifuge *, and the blue flow-
ered Ruellia, or herbe a chandeliers, is used as a sudorific (Belan-
ger)*. In Sennar and Nubia R. nubica Delile, is employed in the
treatment of various diseases '.
Although Ruellia ciliosa Pursh is the only member of the genus
positively identified as a substitute for Spigelia, it is still quite prob-
able that R. parviflora (Nees) Britton and R. slrepens L. also occur
as East Tennessee pinkroot, since all three forms are well distributed
over a large area in the eastern and southern United States. The
habitat, form, and general appearance of the three species are not
sufficiently distinct to render them readily distinguishable to collec-
tors. In view of the fact that R. strepens L. has some well-marked
physiological properties, the possibility of its presence in the crude
pinkroot may in some degree account for the variability in action
which has long been observed in Spigelia.
MINOR ADUITERANTS OF SPI G|ELIA.
Aside from Ruellia the adulterants of Spigelia may be regarded
as accidental, due in the main either to the carelessness of the col-
lector in not sorting out the roots with which the plant would be
associated in its growth, or to a lack of familiarity with the plant on
the part of young or inexperienced collectors. In Spigelia other roots
sometimes occur which have a market value from two to four times
greater than that of the true pinkroot and therefore can scarcely be
regarded as intentional adulterants. Doubtless Some of these are
introduced in the drug lofts where large quantities of various roots
are stored and handled. The worthless roots sometimes present, how-
ever, may have been introduced by the collector with full knowledge
that a fraud was being perpetrated.
A very brief notice of some of these adulterations is all that the
limits of this paper warrant, with the exception of one reputed to be
of great importance but which it is believed rarely, if ever, occurs.
1 ('orre and Lejanne. Itésumé de la Matière Médicale et Toxologique Coloniale,
p. 46, 1887.
2 Baillon, l. c.
3 Corre and Lejanne, l. c. , p. 1 24.
4 Dechambre, l. c.
PHLox CAROLINA. 43
PHLOX CAROLINA.
Mention has been made in the historical account of the fact that
the Carolina phlox was believed to be substituted for Spigelia. In
connection with the observations on the chemistry of the Tennessee
Pinkroot it was shown that the supposed Phlox was probably Ruellia.
There now remains to describe authentic material of this plant and
to show not only that Ruellia as an adulterant of Spigelia has been
wrongly referred to Phlox but also that there are no valid reasons for
believing that Phlox occurs at all, except perhaps in rare cases, as an
adulterant of Spigelia.
Botanical Description.
The Carolina Phlox, formerly known as Phloa carolina L., but
now called Phloa ovata L., is an herbaceous perennial of the family
Polemoniaceae. The simple stems are from one-half to two feet high,
often ascending from a prostrate base. The leaves are opposite and
entire, the upper ones sessile, ovate-lanceolate, with acute tips, the
lower longer, oblong or ovate-oblong, acute, and narrowed into slen-
der petioles. The corolla has a long, slender tube, with a spreading
border of five rounded entire lobes. The color is pink or a delicate
rose-red. The short stamens are unequally inserted on the corolla
tube. A three-parted style terminates the three-celled ovary.
From the thick and branching stem base spring numerous large,
gnarled and crooked, much-branched fibrous roots. These are at first
light colored, becoming dark brown when quite old. The bark some-
times breaks away from the wood in the old roots, but much less freely
than is the case with Ruellia. The roots are thicker and coarser than
those of Spigelia or Ruellia, while in the smaller roots the successive
branches are given off almost at right angles, thus presenting a very
striking characteristic.
Anatomy.
For the anatomical work fresh specimens of Phlow ovata L. were
obtained from authentic plants under cultivation, and material ob-
tained from the United States National Herbarium was used for
comparison. The living material was examined in the spring when
the plants had reached the height of a few inches and again late in
the autumn when they were preparing to enter the winter condition.
44 PINKROOT AND ITS SUBSTITUTIONs.
The aerial stem of the specimens examined was smooth, terete,
and about 2 mm. in cross section (Fig. 17). The pith is large and
central, composed of large parenchymatous cells, in cross section ir-
regularly hexagonal and isodiametric. Toward the periphery of the
pith the cells have thickened walls, while at the center the walls are
thin and cellulosic. Surrounding the pith is a group of cells belong-
ing to the woody parenchyma but not yet lignified. This tissue re-
sembles the internal phloem of Spigelia,
a structure which is not present in Phlox.
The wood is thick, being made up of
thick-walled, more or less regular, simple-
pitted cells, hexagonal in cross section.
The medullary rays are not sharply de-
fined in the younger stages of the stem’s
growth. The vessels are large but not
numerous in the young stems and usually
are more frequent toward the center. The
phloem appears as a narrow discontinu-
ous layer, interrupted by the cells of the
º§: pericycle, which are at intervals contigu
ºù º * - ous with the wood. The pericycle, a con-
tinuous layer of varying thickness, is
formed of thickened cells, irregular or
oval in cross section. The endodermis is
distinct, the cells are large and plainly
Fig. 17. Cross section of , y ºf 2 tº ºn tº & 8 & ; al-o-, -n o'
stem of Phlox o Wata L. show the characteristic thickening of the
a, epidermis: 1), parenchy- lateral walls. The cortex is narrow and
matous cortex ; d, xylem : gº, e te
internal phioem; i. piti. i.e. consists of large, thick-walled parenchy-
dodermis; 1, pericycle: r, thick- e g
waiied pith cells; s, thin-wailed matous cells, irregularly oval in cross sec-
pith cells. X 1 50. g \ . . . . *
tion. The epidermis consists of regular
oval cells, strongly cutinized, and, in all specimens examined, devoid.
of hairs.
The underground portion of the stem differs from the aerial
stem in several important particulars. The pith is large and contains
scattered cells with much-thickened, lignified walls. The wood is less
compact than that of the aerial stem and exhibits large spiral vessels
toward the center. The pericycle is broad and the cells composing it
have thicker walls than the corresponding structure in the aerial stem.
º&
ſº º
s ; ſº
Sº
º
Nº.
Q}s:
º
{ º
º
SO)&#3;
º Wºź. & § ºf }
§§§
tºº
cº, * &\ ºr wº

PII LOX CAROLINA. 45
The relatively thick cortex is composed of regular, elliptical paren-
chymatous cells, among which occur scattered cells with thickened
walls which give a strong lignin reaction. Large intercellulars occur
in the cortex. Outside a corky layer of two or three rows of thin-
walled cells is the epidermis, which Q
is slightly cutinized and composed OCCK) CC &:
of cells with walls thinner than Cººl
those of the epidermis in the aerial (*XL-Q.
stem. P * QC
In the root the fibrovascular Q Xº, 23S
bundle is of the radial type, triarch OK Pº ^
in the young root, and occupies the
center of the stem, there being no 2( Y’
pith. The cells of the xylem are As 2C
thick-walled, hexagonal in cross sec- J2 K )* Ş
tion (Fig. 18), and have simple- <!- «DO Æ
O—º

itted walls. A f t iral Dº-
pitted walls ew scattered spira <S 2 XD NZ
vessels occur in the xylem. A con-
tinuous band of phloem parenchyma 8-2 S7
surrounds the xylem, which in turn Q
is limited by the pericycle, consist-
3.
3
ºC
Sº
G-
ing of two or three layers of large- Čsº-3 O <\
º º º - Cº Yº
sized, thick-walled cells. The endo. ºrjº,
dermis is thin-walled, the cells ex- §º Tºy
hibiting --~~4-> - }{ Lºs &\},
hibiting tangential elongation. ºś
º §§ºß
Large, thick-walled parenchyma- §º f
tous cells comprise the cortex. They §§§
are in general oval in cross section, º
having large intercellular * º º & aſ
8.5 ge intercellular spaces jQC) Q Q\}º
KºśC
between them. Two layers of cells A. º
with brownish walls constitute the
epidermis and exodermis. The cell Fig. 18. Cross section of root of
walls are in close apposition, leaving I?hlox o Wata I,.
e a, epidermis; , b, cortex; d, xylem ;
Il O intercellulars. The cells of the h, spiral vessels; , j, endodermis; 1,
perieyele; t, phloem parenchyma.
outer layer are smaller than those of × 150.
the inner, somewhat elongated tangentially, and externally thickened.
They give rise to the root hairs. The exodermis consists of thin-
walled usually pentagonal cells.
46 PINKROOT AND ITS SUBSTITUTIONS.
Theory, that Phloa is a Substitute for Spigelia.
The first account of the substitution of the Carolina phlox for
Spigelia is given in the report of the Committee on Adulterations and
Sophistications to the American Pharmaceutical Association at its
Twenty-third Annual Meeting in 1875 . A sample of the false pink-
root was sent by the members of this committee to Wallace Brothers,
of Statesville, N. C., who identified it as the root of Phloa Carolina L.,
known with them as the Carolina pink. In the observations made on
this material the roots of the Phlox were described as straight, and
uniform in diameter, with an epidermis easily detached, exposing a
smooth, straw-colored, ligneous thread. This description became
especially significant as the comparative study of the substitutes for
Spigelia progressed, for, as has been stated, it was observed to be a
perfect characterization of the root of Ruellia.
Some years later Maisch “, at a pharmaceutical meeting held in
Philadelphia, referred to the entire or partial replacement of Spigelia
by one or more species of Phlox, principally Phloa carolina L. Since
different species of Phlox as well as Spigelia marilandica were known
in the Southern States as Carolina pink, he suggested that the root
of Phlox may have been first employed and after its virtues had been
learned the root of Spigelia was used. Evidently accepting as assured
the theory of the occurrence of Phlox and wishing to contribute some-
thing to the methods of distinguishing the roots of these plants,
Boynton “published a summary of the results of a comparative analy-
sis of Spigelia marilandica and Phloa carolina.
Trimble assunied that l’hlox was an adulterant of Spigelia, and
after chemical analysis of what he supposed to be Phloa carolina sug-
gested the action of petroleum ether in dissolving certain compounds
from the one but not from the other as a means of distinguishing
them. The honor of the discovery that Phloa carolina was
substituted for Spigelia was claimed by Prof. M. E. Hyams" in 1890.
He states that samples of an invoice received at Philadelphia from
Tennessee were sent to him for identification and were found to be
1 Miller, Mercein, and Peixotto, Proceedings of the American Pharmaceutical
Association, 23: 508—509, 1875.
2 Maisch, J. M. Amer. Jour. Pharm., 55:631-632, 1883.
8 Boynton, W. C. Laboratory Notes. Amer. Jour. Pharm., 56: 570, 1884.
4 Trimble, Henry. An Analysis of the Underground Portions of Phlox Caro-
lina. Amer. Jour. Pharm., 58: 479–482, 1886. e
5 Hyams, M. E. The Crude Drug Industry of the South. The Pharmaceutical
IEra, 4 : 12–15, Jan., 1890.
PII LOX CAROLINA. 47
Phloa carolina L., but that the honor of the discovery was given to
another.
In 1891 Greenish called attention again to the substitution of
Phlox for Spigelia and after microscopical examination described and
figured sections of a sample of root obtained from Professor Maisch,
who stated that he had received it some years before as Phloa caro-
lina. As a means of distinguishing Phlox from Spigelia, Greenish
cites the presence in the cortex of numerous stone cells and cells in-
closing cystoliths composed chiefly of calcium carbonate impregnat-
ing a cellulose skeleton. In tangential sections he observed that the
stone cells were of great length, and that the cystoliths were in gene-
ral cylindrical in shape. These structures were found in the paren-
chymatous tissue of the rhizome and aerial system as well as in
the root.
In his Materia Medica Maisch 4 says that Spigelia “should not
be confounded with the rhizome of Phloa carolina, Linné (like Spi-
gelia known as Carolina pink), which is short, upright, and has a
central pith, hard wood, and brownish-yellow, rather coarse, straight
rootlets containing a straw-colored wood underneath a readily re-
movable bark; benzin extracts from it a crystalline white, tasteless
hydrocarbon.”
The most recent contribution to the literature of this subject is
the study of Phlow carolina made by Morelle & while examining the
falsification of Spigelia. His material, obtained from the Museum of
Natural History at Paris, consisted of the stem and leaves of Phloa.
carolina; the roots of the specimens, however, were wanting. Two
characters which he mentions as serviceable for distinguishing Phlox
from Spigelia are: (1) The structure of the epidermal hairs, and (2)
the presence of rare cystoliths. He finds that the epidermal hairs are
curved, and consist uniformly of a single row of cells. The single
cystolith which he observed was rounded in form and situated in a
sub-epidermal cell extending well into the cortical parenchyma.
Since, however, but a single cystolith was found in all the material he
examined, no importance can be attached to his second characteristic.
91 sºº's;." Note on Plhlox Carolina. Pharm. Jour. Trans., ser. 3,
* Maisch, J. M... A Manual of Organic Materia, Medica, ed. 6, p. 129, 1895.
8 Morelle, E. . Histologie Comparée des Gelsemiées et Spigeliées, p. 13.
These, Paris, 1904. I S, I 4 et seq.
48 PINKROOT \ND ITS SUBSTITUTIONs.
His material was too scanty and fragmentary to furnish a reasonable
basis for diagnostic characters.
Evidence Against the Theory that Phloa is a Substitute for Spigelia.
After an examination of a large number of commercial samples
of pinkroot, a comparison of the structures therein observed with
those described by the authors previously mentioned as characteristic
of Carolina phlox, led at once to the conclusion that in reality these
writers had been working with Ruellia. This belief was supported by
the failure to obtain phloxol from Phlox, and further confirmed by .
careful study of authentic material of Phloa ovata and Ruellia ciliosa.
The straight, wiry rootlets with easily detachable bark noted in the
report of the committee referred to in the preceding chapter, the
stone cells and cystoliths observed by Greenish, the crystalline com-
pound extracted by Trimble, the character of the roots given by
Maisch, and the structure of the epidermal hairs noted by Morelle
are all characteristic of Ruellia ciliosa, while in Phloa carolina there
is an entire absence of similar characters. Among all the samples of
pinkroot examined, a large percentage of which contained other roots
than those of Spigelia, no material was found that could be referred
to Phloa carolina. Material purchased in the market in 1903 for
Phloa carolina proved to be composed entirely of Ruellia.
Through the kindness of Dr. Henry Kraemer, of the Philadelphia
College of Pharmacy, the private collection of crude drugs of the late
Professor Maisch was made available for study during the preparation
of this paper. The material relating to pinkroot consisted of twelve
specimens, a number of which were evidently commercial samples
and were labeled to indicate that they were recognized as substitu-
tions. One specimen labeled “Phlow carolina, substituted in place of
Spigelia” proved on examination to be Ruellia. In the entire collec-
tion no material occurred that could be referred to Phlox.
Specimens of seven different species of Phlox were obtained from
the United States National FIerbarium and examined for cystoliths
and stone cells. In no case were these structures observed, and,
further, the peculiar jointed hairs described by Morelle as occurring
on Phloa carolina, were not present in any of the material examined.
The occurrence of cystoliths in the Polemoniaceae is not noted by
PHLOX CAROLINA. 49
Solereder * in his Anatomy of the Dicotyledons, though he mentions
on the authority of Greenish the finding of cystoliths in a plant char-
acterized as Phloa carolina.
Professor Greenish, on request, kindly sent the writer for study
a specimen of the root which he had received some years since as
Phloa carolina from the late Professor Maisch. This material on
examination proved to be Ruellia and agreed perfectly with the speci-
men labeled “Phloa carolina” in the Maisch collection, of which it had
at one time doubtless formed a part. Although Solereder in effect
questions the identity of the plant reported on by Greenish, his refer-
ence to it in connection with the description of the Polemoniaceae has
apparently engendered the view that cystoliths occur in that family.
From the evidence at hand this view must be entirely discredited,
since the material used by Greenish in his study was not Phlox but a
species of Ruellia.
No contributor to the theory of the substitution of Phlox seems
to have secured authentic living material for his study, but to have
taken it for granted that the adulterant occurring in roots sold as
Spigelia had been correctly identified as Carolina phlox, Phloa ovata.
By whom the supposed identification was made, or what the method
of determination was, is not now possible to learn. The error has been
made and widely copied and now appears in almost every text-book or
work of reference which mentions the medicinal properties of Spigelia.
A careful study of the literature of Spigelia, an examination of
the drug now occurring on the market, and in particular the com-
parative histology of Spigelia, Phlox, and Ruellia must lead to the
conclusion that Phlox rarely or never occurs as a substitute for Spi-
gelia, and that the root so generally described and studied as Phlox
must be referred to Ruellia.
Medicinal Properties of Phloa.
There is no evidence at the present time that Phlox has any
medicinal value. Lindley in 1831 said of the Polemoniaceae that
their properties were none or unknown. According to Culbreth *,
Phloa carolina is allied to Spigelia and is a good anthelmintic, as is
1 Solereder, H. Systematische Anatomie der Dicotyledonen, p. 622, 1899.
2 Tindley, John. Introduction to the Natural System of Botany, p. 216, 1831.
3 Culbreth, D. M. Materia, Medica, and Pharmacology, p. 448, 1900.
50 PINKROOT AND ITS SUBSTITUTIONS.
likewise Phloa glaberrima. It has not been possible, however, to
verify the source of this information.
In the Maisch collection of crude drugs is a sample received from
Sparta, Ga., in 1883, which bears the label “Phloa glaberrima Lin.,
Sold as Pink Root.” Examination revealed that the roots were
neither Phlox nor Ruellia. It has been suggested that Phloa ovata
was used as an anthelmintic before Spigelia was adopted, and since
pinkroot has been regarded as being sometimes replaced by Phloa.
glaberrima, the inference was probable that the latter was a good
anthelmintic. Until some careful investigations shall have determined
the properties of Phloa glaberrima, it, as well as Phloa ovata, can not
be regarded as possessing any medicinal value, and must be omitted
from the category of medicinal plants.
IMPURITIES.
The roots of the following plants sometimes occur intermingled
with those of Spigelia, but are impurities rather than adulterants.
As has been suggested, these may be introduced accidentally in the
drug lofts, or through carelessness on the part of the collector. Upon
consideration of the fact that some of these roots, such as Serpentaria
or goldenseal, are themselves usually worth from three to five times
as much as Spigelia, it does not seem that they would knowingly be
introduced as an adulterant of pinkroot.
Saponaria officinalis L. Hagen" says that Saponaria officinalis L.
sometimes takes the place of Spigelia in the markets, but that it may
be distinguished by its three-nerved leaves. This plant scarcely de-
serves mention as an adulterant of Spigelia, since it rarely, if ever,
occurs in American markets; but if present it may be readily dis-
tinguished from the true pinkroot by the greater size of the root and
the general habit of growth, which do not at all resemble Spigelia.
Aristolochia serpentaria L. Serpentaria is indicated by numer-
ous modern materia medicas as possibly confused at times with Spi-
gelia, from which, however, it may be readily distinguished. The
pith of the rhizome is eccentric, being nearest the upper side, while
broad medullary rays separate the wood into prominent wedges. The
1 Hagen, cited by Berg. Pharmakognosie des Pflanzen- und Thierreichs, pp.
263—264, Berlin, 1879.
PHLOX CAROLINA. 51
odor is aromatic, resembling that of turpentine, and is alone sufficient
to distinguish the plant from pinkroot.
Hydrastis canadensis L. The root of goldenseal (Hydrastis
canadensis L.) has been reported as an adulterant of Spigelia, but not
to any great extent. As much as 6 per cent has been detected. The
yellow rootlets and the large rhizome with lemon-yellow interior serve
to distinguish it readily.
Dioscored villosa L., wild yam root; and Collinsonia canadensis
L., stone root, sometimes occur as impurities, but may be easily de-
tected, usually, by their well-known gross structure and general ap-
pearance.
MICROSCOPIC EXAMINATION OF SPIGELIA AND ADUL-
TERANTS.
Ruellia is the only important adulterant found in Spigelia, since
the other plant parts sometimes present occur almost wholly as im-
purities. On this account a simple preliminary examination may
serve to show the character of material offered as pinkroot, since
Ruellia differs very markedly in appearance from Spigelia and is
easily separated from it. If unground roots or rhizomes are to be
examined they should be placed for a time in water to soften the tis-
sues and render them less refractory to the knife in cutting. Thin
sections cut with a sharp scalpel or section razor may be floated out
on a drop of water on a glass slide and readily examined with a micro-
scope or good hand lens. A comparison of the structures observed
with those of Spigelia, Ruellia, and Phlox (see Figs. 4–9, 11—18)
will readily serve to identify the section. The structures under obser-
vation may be rendered more distinct by the use of zinc chloro-iodid.
When the application of a drop of this reagent to the section is fol-
lowed by the development of an intense blue color, particularly in the
pith of the rhizome, Spigelia is indicated. If no blue color appears
and large stone cells and cystoliths are seen in the cells of the cortex
the material is Ruellia. Since other roots or rhizomes are also said to
occur mixed with Spigelia, from which close examination may be
required to distinguish them in materials purporting to be pinkroot,
the following key is offered for their separation:
52. PINKROOT AND ITS SUBSTITUTIONs.
Cystoliths present . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ruellia.
Cystoliths wanting.
Starch present . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spigelia.
Starch wanting.
Corky layer 1-3 cells thick or wanting. . . . . . . . . . . ‘. . Phlox.
Corky layer 3 to many cells thick. . . . . . . . . . . . . Saponaria.
A differentiating character is presented, however, by the starch
grains, since starch is absent from the adulterants mentioned above.
However, the fineness of the starch grain and its lack of striking
characters, render uncertain its identification among many other plant
starches which might be readily introduced in the powdered drug.
These starch grains measure about 4 p and in powdered pinkroot are
associated with parenchyma cells and long, light-colored Sclerenchyma
fibers. Ruellia always reveals its presence by the numerous stone
cells and cystoliths which frequently remain intact even in finely
powdered material. Powdered samples of the underground portions
of the Phlox at hand gave no reaction for starch. The absence of
starch from a powder supposedly made of pinkroot suggests at once
that the material is not Spigelia. On the other hand, the presence of
starch while indicative of Spigelia is by no means conclusive of its
presence. “”,”
“ Users of pinkroot can best secure a pure article by purchasing
the cytide'drug and subjecting it to a rigid examination, using the
mièroscopé when necessary to verify all doubtful material until the
gróss characters are well enough learned to permit accurate deter-
mination by observing the macroscopic character of the roots.
is
CoMMERCIAL ASPECTs of PINKROOT. , 53
COMMERCIAL ASPECTS OF PINKROOT.
Although pinkroot occurs over a wide area in the eastern half of
the United States, it is not now found north of Virginia and Ken-
tucky in sufficient abundance to make profitable its collection as a
drug root. Since its introduction to the settlers of the Carolinas as a
vermifuge it has been regarded as a plant belonging essentially to the
Southern States. Its special properties caused it to be sought for and
collected by the Indians who early inhabited this region, especially
the Creeks and Cherokees of Georgia. When pinkroot first came into
use the entire plant was employed. This was pulled up by the Indians
and after being dried was packed in bales and bartered to the whites.
As the settlers pushed westward, new fields of supply opened in the
region adjacent to the Mississippi River. For many years the States
east of that river furnished practically all the pinkroot that entered
the market, but under the stimulus of the high prices obtainable in
1862-3 new sources of supply were opened in Arkansas and now the
Southwestern States produce a large part of the drug annually sent
into commerce at New Orleans and St. Louis. &
The method of collection has changed somewhat with time, and
now there is collected the official part only, consisting of rhizome and
roots. These, after being freed from dirt as much as possible, are
carefully dried and packed in bales or casks for shipment to the
market. Pinkroot that has been thoroughly dried and then packed in
casks has frequently been preferred to the root put up-in bales, since
the casks not only protect the root from dampness, which of itself
causes deterioration in quality, but also largely diminish the tendency
to mold, which is frequent in bales that have become damp. Former-
ly, when space was not so valuable in storage and shipment, crude
drugs were sent into commerce packed in flour barrels or made up in
loose bales. Now an effort is made to compact the material as much
as possible, and some collectors of crude drugs utilize the cotton
presses readily accessible to almost every southern farmer to compress
54 PINKROOT AND ITS SUBSTITUTIONS.
drug leaves or roots into firm bales. This treatment saves in the cost .
of handling and storing and also by tending to exclude the air from
the bales reduces the absorption of moisture and consequent deterio-
ration.
Market quotations show that the demand for pinkroot, though
quiet, is steady, and prices from year to year show only fluctuations
consistent with the general movement of crude drug prices. The
highest price recorded for pinkroot was reached in 1862-3, when it
sold for $3.25 per pound, quality receiving scant consideration so
long as the material could be called pinkroot. It was reported as the
scarcest of all drugs in 1863, the lack of supply and consequent high
prices probably being due to the interruption of trade incident to the
hostilities between the North and the South. In the latter part of
1863 the price per pound declined to $1.50, and 1864 saw a further
decline to $1.25, with the supply small and the quality only fair. By
August, 1870, the price had fallen to 30 cents, but rose again the next
year to 50 cents, dropping back in 1872 to 38 or 40 cents a pound.
Prices in 1874 were a little higher, due possibly to the financial panic
of the previous year which decreased the volume of business and
caused a severe shrinkage in the quantity of crude drugs entering the
market. In 1886-7 prices had risen to 40 to 50 cents, and in 1895
they had declined to 18 to 27 cents a pound. According to the Oil,
Paint and Drug Reporter, the range of prices of pinkroot for the
decade ending with 1904, was from a maximum of 27 cents in 1895
to a minimum of 17 cents reached in 1903 and again in 1904. In
November, 1905, the price advanced to 45 cents, and in June, 1906,
the price was quoted at $1.00 to $1.25 per pound.
The market supply of pinkroot, in common with other crude
drugs, is variable, since the greater number of collectors do not make
a regular business of gathering drugs, but take up the work when
otherwise unemployed or when prices have become attractive. Prices
naturally accomodate themselves to the supply, and a season of vigor-
ous collecting is apt to be followed by a declining market. This in
turn tends to diminish collection and causes a shrinkage in supply,
which is in turn followed by increasing prices as the demand quickens.
In the widespread adulteration of crude drugs, to which pinkroot
forms no exception, lies a factor which undoubtedly has a marked
effect on the market price. In many cases the presence of the adul-
COMMERCIAL ASPECTS OF PINKROOT. 55
terant has been recognized and due allowance made for it in deter-
mining the quality of pinkroot. However, the fact that Ruellia has
So far supplanted the real drug as to be studied and described as
pinkroot shows that in the majority of cases in which the adulterant
was present it has been undetected. When this fact is recognized it
no longer appears strange that Spigelia has been credited with being
a drug of very uncertain and variable action. In hundreds of cases in
which pinkroot has been prescribed, an extract of Ruellia has in
reality been given and the results of its action—good or bad—have
been attributed to Spigelia. Fortunately, Ruellia apparently possesses
no properties which in the doses usually administered give very
marked physiological action. The menace, however, to the well-being
of the patient by the use of adulterated drugs is a double one, for not
only is he deprived of the remedy which is indicated in his peculiar
ailment, but there are administered to him plant principles with the
nature and action of which neither physician nor patient may be
familiar. -
The rigid exclusion of adulterated or false pinkroot from the
markets may operate to further increase the price, which is now ab-
normally high. However, the effectiveness of the drug as a whole
should thereby be so increased that the result would be a distinct
economic gain.
I desire to gratefully acknowledge the generous suggestion and
criticism of Dr. Rodney H. True throughout the preparation of this
paper.
Washington, D. C., June 1, 1906.
56 PINKROOT AND ITs SURSTITUTIONS.
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directed to numerous plants of the island used as domestic remedies.
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6. History of the Art of Distillation and of Distilling Appara-
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MONOGRAPHS. —Continued.
» (In course of preparation.) -
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-*—-tº---—a
BIBLIOGRAPHIES.
1. Chemical Biography of Morphine. From 1875 to 1897, with
an index of authors and subject index. By H. E. Brown. Pamphlet,
pp. 60. + $0.40
2, Santonin. Bibliography, with abstracts of methods of production
etc. From 1830 to 1897. By A. Van Zw aluwenburg. Pamphlet.
pp. 11. • $0.10
3. Bibliography of Apiol. From 1855 to 1896. By A. Van Zw a-
luwenburg. Pamphlet, pp. 4. $0.05
4. Bibliography of Spirit of nitrous ether, and ethyl nitrite.
Up to 1899. By W. O. Richtmann and J. A. Anderson.
Brochure, pp. 180. $1.00
5. Bibliography of aromatic waters. From 1809 to 1900, incl.
By W. O.TRichtmann. Brochure, pp. 219. $1.00
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cated by the following fascimile reproduction of such a card.
* Q

A RBViſw ºf the liſt|ſaillſ, Oll illº Estimatiºn
ºf Alkali's fir is Yu 1905,
By W. A. PUCKNER.
MILWAUKEE,
Pharmaceutical Review Publishing Co.
1907.
FU ELICATIONS
...by the....
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MONOGRAPHS.
No. 19.
MIL WAUKEE,
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1907.
A Review of the Literature on the Estimation
of Alkaloids for the Year 1906.
By W. A. PUCKNER.
M I LVVAUKEE,
Pharmaceutical Review Publishing Co.
1907.
Ó2 8%r,
*-/o-/?
The year 1905 having brought forth the eighth decennial revision
of the United States Pharmacopoeia, it was to be expected that the
year 1906 would bring out a critical review of the methods of esti-
mating alkaloids contained in the book and the alkaloid standards
laid down. To no small extent, the interest in these methods and
ständards is due to the formal recognition which the pharmacopoeia
has received in the Pure Food and Drugs Act, June 30, 1906, and the
expected enforcement of the act. *
Murmurs of discontent with the newly adopted methods cul-
minated in what might be called an indignation meeting when the
Section on Scientific Papers of the American Pharmaceutical Asso-
ciation at the Indianapolis meeting took up the subject. As a basis
for discussion that portion of the report of the Committee on
the United States Pharmacopoeia was read which referred to alka-
loidal standards and methods of standardization. The discussion
opened with the presentation of a resolution requesting the Revision
Committee of the United States Pharmacopoeia to examine the of—
ficial assay processes and, if found desirable, to publish a supplement
to the Pharmacopoeia containing changes deemed important. A
general discussion followed in which the weak points of the official
assay processes were emphasized with only an occasional word of
praise for their advantage. In the main it appeared that the methods
were faulty in detail rather than principle. In the end the chairman
of the Revision Committee of the United States Pharmacopoeia ex-
plained that this committee had authority to make necessary changes
and promised that the modifications and corrections proposed would
be considered and any errors in the official methods of assay corrected.
* Report of Com, on U. S. P. Proc. A. Ph. A., 1906, vol. 54, p. 437.
2
Alkaloidal Standards. Publications in regard to the practi-
cability of the standard adopted for fluid extracts in the U. S. P. 8 °,
the quality of the alkaloidal drugs on the market “, the preparation of
tinctures from assayed drugs or from fluid extracts * and the relation
between the assay standard for the drug and its preparations" will
be noted as they apply to specific drugs.
Apparatus. F. R. Eldred" proposes a new assay percolator,
similar to the one proposed by H. M. Gordin ", designed to permit in
one container the maceration and the subsequent percolation pre-
scribed in the pharmacopoeia for the assay of many drugs. H. M.
Gordin * has designed two separatory funnels. No. 1 has two outlets
and permits either the aqueous or the ethereal liquid to be drawn off
Without contamination of the immiscible solvents. No. 2 is so con-
structed that it may be used as a distilling flask or as a separatory
funnel.
Herman Gardner * has devised a bottle for the precipitation of
morphine in opium assays calculated to facilitate its removal and to
minimize the liability of loss.
General Methods. D. Jonescu " adapts to the estimation of
quinine and caffeine (also antipyrin) the method of H. Thoms”
based on the precipitation of alkaloids with potassium-bismuth iodide
Solution, decomposition of the precipitate with alkali and extraction
of the alkaloid with ether. Using 1 gm. of alkaloid they recovered
0.9405 gm. quinine and 0.9546 gm. caffeine.
H. Matthes and Otto Ramstedt "º also have studied the method
of Thoms. They compare the results by this method when applied to
Cxtracts of coca, belladonna and henbane with the result obtained with
other methods. While the Thoms’ method gives good results it is too
complicated. The authors also take up the estimation of tannin and
organic acid in marcotic extracts as proposed by Thoms, and conclude
* IReport of Com. on U. S. P. Proc. A. Ph. A., 1906, vol. 54, p. 437.
* Iłeport of Com. on Drug Adulteration, I’roc. A. Ph. A., 1906, vol. 54, p. 329.
* IReport of Com. on U. S. P. I’roc. A. Ph. A., 1906, vol. 54, p. 444.
* Frank X. Moerk, Proc. Pa. I’harm. Asso., 1906 (Am. J. Pharm., 1906, vol. 78,
l
sº J. Am. Chenn. Soc., 1906, vol. 28, p. 187 (I’roc. A. Ph. A., 1906, Vol. 54,
p. 99.
* I’roc. A. Ph. A., 1905, vol. 53, p. 386.
* Proc. A. L’h. A., 1906, vol. 54, p. 378.
* I'harm. J., 1906, vol. 76, p. 548.
* Ber, d. d. pharm. Ges., 1906, vol. 16, p. 130.
** Pharm. Rev., 1906, vol. 24, p. 233.
* I'harm. Ztg., 1906, vol. 51, p. 1031.
5
*
9
p. 3
y
X
)
j
3
that, with the present knowledge of the constituents of vegetable
drugs, these determinations are of little value.
A comparison of the method of Thoms with the methods of the
German and the Austrian pharmacopoeia appears below (see Bella-
donna).
Edward Schaer “ discusses the solubility of alkaloidal salts in
immiscible solvents and outlines the result of an extended series of
experiments made by A. Simmer under his direction. With the ex-
ception of a few “weak” alkaloids such as caffeine and colchicine, it
was generally held that alkaloids in the free state (alkaloid hydrox-
ides) were soluble in ether, chloroform, etc., while alkaloid salts were
insoluble in these solvents. More careful work has shown that this is
true only in a general way. The solubilities of alkaloids are largely
dependent on two properties. First, alkaloid salts when dissolved in
water are hydrolized into free acid and alkaloid hydroxide and the
latter or its anhydride dissolves in the immiscible solvent. The ex-
tent to which this occurs depends on the basic strength of the alkaloid
and on the strength of the acid combined with it; an excess of acid
decreases or prevents it. Second, many alkaloid salts are, themselves,
soluble in chloroform and, though to a less extent, in ether. This is
true especially of the chlorides and in recognition of this sulphuric
acid, and not hydrochloric acid, is used to abstract alkaloids from
their chloroform solution in the valuation of drugs. Schaer gives the
behavior of alkaloids when combined with different acids and also the
action of immiscible solvents other than ether and chloroform.
A. Simmer “ details some of the work above referred to by
Schaer. Experiments are also reported on the decomposition of alka-
loids by chloroform and the decomposition of chloroform by alkaloids.
In the latter case hydrochloric acid is formed.
H. M. Gordin " notes that some of the official assay methods
“do not work” and that some are too complicated. He proposes a
modification of the official method for belladonna patterned after the
processes of the German Pharmacopoeia, but in which sodium car-
bonate or sodium hydroxide instead of ammonium hydroxide is used
to sel, free the alkaloid from the aqueous solution of its salts. While
ammonium hydroxide is taken up by chloroform or ether-chloroform,
13 Proc. A. Ph. A., 1906, vol. 54, p. 425.
11 Arch d. Pharm., vol. 244, p. 672, from Chem. Centrbl., 1907, 1, p. 827.
15 Proc. A. Ph. A., 1906, vol. 54, p. 377.
*
4
the fixed alkalies are not soluble and hence the alkaloid may be
titrated in this solution after partial distillation to expel the traces of
ammonia carried over from the drug. Using the specially constructed
separatory funnels, described above, the method is stated to be simple,
short and exact. The details for the valuation of aconite, ipecac and
for fluidextracts of pilocarpus, cinchona and physostigma are noted
below.
Indicators. A. B. Lyons * and J. M. Francis " condemn the
adoption in the pharmacopoeial assay processes of hematoxylin as
indicator in the titration of alkaloids and believe that cochineal is to
be preferred. C. E. Vanderkleed" describes the method of using
iodeosin in the titration of alkaloids. For the titration of morphine
Bernström * recommends iodeosin, while Asher * uses hematoxylin.
Aconite. The official method for the valuation of aconite has
been criticised because it is tedious; thus, in discussing this subject
at Indianapolis “, C. E. Caspari stated that the filtration of the
aqueous liquid required more than three days; this Chas. Caspari, Jr.,
overcomes by the use of pumice, but J. M. Francis believes that it is
contrary to law to so modify the official method. Similar criticisms
of the official assay process have been made by W. T. Hankey *
H. M. Gordin *, using specially constructed apparatus (see Ap-
paratus), sets free the alkaloid with sodium carbonate and extracts it
with a mixture of three volumes of ether and one of chloroform.
As regards the alkaloidal content of aconite (root) the committee
on Drug Adulteration reports * assays showing variations, from 0.20
to 0.65 per cent. with an average of 0.51 per cent. G. Fromme *
reports that five lots assayed 0.530, 0.617, 0.638, 0.775 and 0.797 per
cent., an average of 0.631 per cent. Comments on the official standard
for fluidextract of aconite received by the Committee on U. S. Phar-
macopoeia * indicate that the standard can readily be maintained.
Belladonna, Hyoscyamus and Strammonium. Karl Diet-
rich * has compared the assay methods for extracts of belladonna and
10 Proc. A., Ph. A., 1906, vol. 54, p. 441.
17 Proc. A. Ph. A., 1906, vol. 54, p. 454.
18 Apothecary, 1906, vol. 54, p. 510.
19 Pharm Centralhalle, 1906, vol. 47, p. 632.
20 Western, Drug., 1906, vol. 28, p. 453.
* Proc. A. Ph. A., 1906, vol. 54, p. 455-6.
* Am. Drug., 1906, vol, 49, 1, p. 360.
*8 Proc. A. Ph. A., 1906, vol. 54, p. 379.
* Proc. A. Ph. A., 1906, vol. 54, p. 333.
* Caesar & Loretz, Geschäfts-Bericht 1906, p. 70.
* Proc. A. Th. A., 1906, vol. 54, p. 438.
*7 IIelfenberger Annalen, 1905 (Pharm. Centralhalle, 1906, vol. 47, p. 916).
:5
hyoscyamus in the new Austrian pharmacopoeia, the German pharma-
copoeia and the bismuth method of Thoms (see General Methods).
The method of the Austrian pharmacopoeia directs the extract to be
dissolved in little water and then diluted with much alcohol. An
aliquot part of the clear solution is diluted with water and heated on a
water bath to expel the alcohol. The residual solution is rendered alka-
line with sodium carbonate and extracted with chloroform. From the
chloroform solution the alkaloid is extracted with very dilute hydro-
chloric acid. The hydrochloric acid solution of the alkaloid is ren-
dered alkaline with sodium carbonate and the alkaloid abstracted with
chloroform. The chloroform is evaporated at room temperature, the
residue dried at 100 degrees C. and weighed. The results obtained
with this method agree closely with those obtained with the Thoms’
method. The results by the method of the German pharmacopoeia
are liable to be excessive because bases other than alkaloids are esti-
mated. The potassium-bismuth iodide method of Thoms was applied
to extracts of belladonna and of henbane as follows: To 4 gm. of dry
cxtract (extractum siccum) are added 50 cc. 90 per cent. alcohol, the
mixture shaken frequently during 3 hours and filtered. Then 25 cc.
of the filtrate, taken to represent 2 gm. extract, are heated on a water
bath until the alcohol has been driven off. The residue is taken up
with 50 cc. water and to this added 10 cc. 10 per cent. Sulphuric acid
and 5 cc. potassium-bismuth iodide solution (prepared by pouring a
solution of 80 gm. bismuth submitrate in 200 gm. nitric acid, sp. gr.
1.18, into a concentrated solution of 272 gm. potassium iodide in
water and, after removal of potassium nitrate crystals formed, dilut-
ing to 1000 cc.) The precipitate is collected and with the filter
placed in a cylinder and treated with 20 cc. 15 per cent. sodium.
hydroxide solution and 10 gm. coarsely powdered crystallized sodium
carbonate. Next 50 cc. ether are added and the whole shaken fre-
quently during three hours. Now about 100 cc. water, 20 cc. ether
and 5 drops iodeosin solution are measured into a stoppered flask and
any red color, due to the alkalinity of the glass, destroyed by addition
of a few drops of hundredth normal hydrochloric acid. To this 20 cc.
of the ethereal alkaloid solution, representing 1 gm of extract, are
added and its alkalinity determined with one-hundredth normal
hydrochloric acid.
6.
G. Fromme * reiterates that for chlorophyl-bearing drugs higher
figures are obtained when the drug is extracted with ether or chloro-
form and ether in presence of alkali, the ether or ether-chloroform
Solution of the alkaloid extracted with a known excess of volumetric
acid, the excess of acid determined and the amount of alkaloid cal-
culated from the volume of acid consumed. In part these high results
are due to ammonium compounds contained in the drug from which
ammonia is liberated, carried over and estimated. But in part,
Fromme believes the error may be due to the presence of oils, fats or
waxes in leaf drugs which are saponified by alkali forming soaps
which are soluble in ether, etc. If such an ether or ether-chloroform
solution is extracted with volumetric acid a portion of the acid will
be used up in the decomposition of the soap. A considerable series of
experiments are reported showing that, when belladonna leaves or
henbane leaves are macerated with ether and sodium hydroxide, high
results are obtained unless the ether solution is brought to complete
dryness prior to the titration.
- Another comprehensive series of experiments is offered relative
to the decomposition of mydriatic alkaloids. It is concluded that these
alkaloids may be combined with acid and again liberated in the free
state with no or at least very slight decomposition and that from an
alkaline aqueous solution chloroform extracts the alkaloids completely.
W. T. Hankey *" criticises the U. S. P. assay method for bella-
donna leaves. He also reports that the alkaloid content of ten lots of
belladonna leaves ranged from 0.230 to 0.516 per cent, with an
average of 0.334 per cent. Reports on the alkaloidal value of bella-
donna leaf and root are also made by the A. Ph. A. Committee on
Drug Adulteration * and the A. Ph. A. Committee on U. S. Phar-
macopoeia *. G. Fromme * reports the assay of 10 lots of belladonna
root ranging from 0.07 to 0.94 per cent., with an average of 0.65 per
cent. Another report" states that three lots of belladonna leaves
assayed 0.40, 0.36 and 0.37, and 7 lots of belladonna root ranged from
0.55 to 0.38, averaging 0.48 per cent. Reports on the alkaloidal value
* Caesar & Loretz, Geschäfts-Berſcht, 1906, p. 24.
; fl.º.º. 384.
i. IProc. A. Ph. A., 1906, vol. 54, p. 438.
* Caesar & Loretz, Geschifts-Bericht, 1906, p. 45.
Smith, Kline & French, Report for 1906, p. 13.
7
of hyoscyamus and strammonium are made by the A. Ph. A. Commit-
tees on Drug Adulteration * and on U. S. Pharmacopoeia *.
Cinchona. J. M. Francis " and A. B. Lyons * criticise the
U. S. P. assay process, especially as regards the determination of
cther-soluble alkaloids. Lyons raises the important point that tem-
perature materially influences the determination of ether-soluble alka-
ioids and recommends that the liquids should be cooled to 15 degrees
C. and kept at this temperature during the digestion. He also recom-
mends that the mixture be shaken continuously and not “at intervals”
as now specified. & *
In the U. S. P. valuation of fluidextract of cinchona the fluid-
extract is shaken with ether, chloroform and ammonia water, and an
aliquot part taken for the determination. Considering the use of
aliquot parts of ethereal liquids objectionable whenever it can be
avoided, H. M. Gordin * modifies the official process by adding to
5 cc. of fluidextract, 2 cc. of a 10 per cent. sodium hydroxide solution
and extracting with three portions, 25 cc. each, of a mixture of three
volumes of ether and one volume of chloroform. The ethereal solu-
tion of alkaloids is shaken out with three portions of dilute sulphuric
acid. The sulphuric acid solution is made alkaline and extracted with
chloroform. The chloroform is evaporated from a tared vessed and
the residue dried and weighed. * *
A. Panchaud “” has determined that cinchona alkaloids readily
decompose chloroſorm according to CHCl2 + 0 = COCl, -- FICl.
If cinchona alkaloids are dissolved in chloroform in the evening and
titrated the next morning, from 20 to 100 per cent. of the alkaloid
will be found to have been neutralized by the hydrochloric acid pro-
duced in the decomposition of the chloroform. Since the decomposi-
lion of 0.0229 gm. chloroform will produce sufficient hydrochloric
acid to neutralize 0.120 gm. alkaloids, the error liable to be introduced
thereby in the volumetric estimation of cinchona alkaloids is obvious.
Panchaud therefore cautions that any solution of cinchona alkaloids
which contains chloroform must be evaporated at once.
* Proc. A. Ph. A., 1906, vol. 54, pp. 337 and 347.
* I’roc. A. Ph. A., 1906, vol. 54, pp. 430 ànd 440.
* Proc. A. Ph. A., 1906, vol. 54, p. 453.
* Proc. A. Ph. A., 1906, vol. 54, p. 440.
98 Proc. A. Ph. A., 1906, vol. 54, p. 380.
º lºve; Wochenschr, f. Pharm., vol. 44, p. 580 (Chem. Centrlbl., 1906, 2,
p. 1212).
8
N. Matolesy” proposes the use of amyl alcohol for the extraction
of cinchona alkaloids in place of chloroform and ether. Amyl alcohol
when shaken with the sodium chloride solution increases about one
per cent. in volume; he directs, therefore, that the aqueous solution
be saturated with sodium chloride and that a correspondingly smaller
volume of amyl alcohol be used in the assay; thus, instead of 60 cc.
only 59.4 cc. are directed. The following method is proposed: 4 gm.
of powdered drug are boiled with 30 cc. water to which have been
added a few drops diluted hydrochloric acid. The mixture is filtered
and sufficient water poured through the filter to produce 50 cc. of
filtrate. The filtrate is rendered alkaline with milk of lime and then
treated with 59.4 cc. amyl alcohol. 20 gm. of sodium chloride are
added to the liquid, the mixture shaken until saturated and the two
liquids permitted to separate, using a centrifuge to facilitate the
separation. Now 30 cc. of the amyl alcohol solution is pipetted off,
cvaporated to dryness and the residue dried at 100 degrees. To deter-
mine in this residue of total cinchona alkaloids the amount of
quinine and quinidine it is dissolved in a little hydrochloric acid,
diluted to 50 cc. and rendered alkaline with sodium hydroxide. 20
gm. sodium chloride and 20.2 cc. absolute ether are now added and
mixed by shaking. 10 cc. of the ether solution are pipetted into a
tared vessel, the ether evaporated and the residue dried at 100 degrees.
For the determination of total cinchona alkaloids, the following
short method is proposed : " 2.5 gm. powdered cinchona are digested
for about one hour with 10 cc. water and 2 cc. 25 per cent. hydro-
chloric acid, at a temperature of 40 to 45 degrees. The mixture is
allowed to cool, 65 gm, ether-chloroform mixture (3:1) added,
shaken once and then the acid neutralized with 7 cc. 15 per cent.
sodium hydroxide solution. Now one gm. powdered tragacanth is
added, and the mixture shaken thoroughly, until the powder agglut-
inates and the ether-chloroform is perfectly clear. The ether-chloro-
form is poured through a dry plated filter, and 52 gm. (= 2 gm.
drug) extracted with four portions, 10 cc. cach, of one to two per cent.
hydrochloric acid. The united hydrochloric acid extractions are ren-
dered alkaline with sodium hydroxide and extracted with 20, 10, 5,
5 cc. chloroform. The united chloroform extractions are evaporated
40 Pharm. Post, 1906, No. 22 (Pharm. Zig., 1906, vol. 51, p. 612
).
41 Jahresbericht der Firma Philipp Röder in Wien-Klosterneuburg (Pharm.
Ztg., 1907, vol. 52, p. 354).
9
in a lared flask and dried for two hours at 100 degrees. The weight
obtained multiplied by 50 gives the per cent. of total alkaloids.
Florence * proposes two methods for the valuation of cinchona;
one a short method giving approximate results, the other, an exact
method. In the short method 12 gm. finely powdered drug are mixed
with 120 gm. pure alcohol-free ether, then 10 cc. 10 per cent. Sodium
hydroxide solution is added, the flask stoppered and shaken repeatedly
during one hour. Then 10 cc. water are added and, when the liquids
have formed separate layers, the ether is poured off. The ether is
extracted with 20 to 30 cc. lime water, whereby the resinous matter
is separated and the liquid rendered almost colorless. 100 gm. of the
ethereal liquid are transferred to a wide-necked stoppered flask, 30 cc.
water, added and then tenth-normal ethereal oxalic acid solution (pre-
pared as needed by dissolving 0.63 gm. pure crystallized oxalic acid in
sufficient ether to make 100 cc.), run in until it causes no further
turbidity or until a drop placed on litmus paper shows neutrality.
In this way the alkaloids are completely precipitated in the form of
oxalates, dissolving with the exception of quinine oxalate in the
ether. To obtain the weight of total alkaloid in 10 gm. drug the
number of ce. of oxalic acid solution is multiplied by 0.35, experi-
ments having shown that this is the weight of cinchona alkaloids
precipitated by 1 cc. of ethereal oxalic acid solution. For the deter-
mination of quinine the precipitated quinine oxalate is collected on a
tared filter, washed well, dried and weighed. 1 gm. Quinine oxalate
corresponds to 0.878 gm. pure quinine. *
In the exact method the drug is treated in an extraction appa-
ratus with a mixture of ether, four parts, and chloroform, one part,
until a portion of the percolate is not rendered turbid-by addition of
ethereal oxalic acid solution. The ethereal liquid is then extracted in
a separatory funnel with three portions of lime water, the latter ex-
tracted twice with a little ether. The ethereal liquids are united.
brought to dryness and the residue weighed as total alkaloids. To
determine the quinine the total alkaloids are dissolved in ether, or in
ether to which one-fifth its volume of chloroform has been added, and
30 cc. of an aqueous saturated solution of quinine oxalate and then the
quinine precipitated with the ethereal oxalic acid solution as in the
short method. The ether is decanted to a tared filter, then the precipi-
* Bull. des scienc. pharmacolog., 1906, 365 (Pharm. Centralhalle, 1907, vol.
48, p. 405). *
1()
late transferred to the filter and Washed with a saturated solution of
quinine oxalate until the washings are rendered no more turbid on
the addition of lime water than a saturated solution of quinine oxalate
when treated in the same way. The precipitate is allowed to drain,
the filter and precipitate pressed between filter paper to absorb most
of the retained wash fluid and weighed. It is then dried, finally at
100 degrees C. and again weighed. Since 1 cc. water dissolved 0.00069
gm. quinine oxalate there is subtracted from the last weight 0.00069
gm. for every gm. difference between the first and second weight and
also the weight of the filter—the remainder is the weight of quinine
oxalate. The quinine oxalate solution is prepared by treating quinine
sulphate with sodium hydroxide and ether, precipitating the ether
solution of quinine with an ether solution of Oxalic acid, collecting
the precipitate, washing it with ether and drying it.
For the determination of the amount of quinine in wine, J.
Evan * gives directions, g
Coca. A comparison of several assay methods by Matthes and
Ramstedt has been noted under “General Methods.” The A. Ph. A.
Committee on the U. S. Pharmacopoeia * and the A. Ph. A. Commit-
tee on Drug Adulteration” report on the alkaloid content of the drug.
Coffee, Guarana, Kola, etc. The details of estimating caf-
feine in pharmaceutical products has received some attention. C. E.
Vanderkleed and J. L. Turner * have worked out the details for the
estimation of caffeine in effervescing salts. F. Zernik “ has deter-
lmined the composition of Migrainin, a mixture of caffeine and anti-
pyrin, and its substitutes. To estimate caffeine, he dissolves Migrainin
in a concentrated aqueous solution of potassium nitrate and precipi-
lates the antipyrin by addition of an acid solution of mercuric nitrate.
From the filtrate the caffeine is extracted with chloroform, the chloro-
form evaporated and the residue dried at 90 degrees. Since the resi-
due was found to contain small quantities of antipyrin-mercuric
nitrate, it was dissolved in water acidulated with nitric acid and the
mercury precipitated by means of hydrogen sulphide and weighed as
mercuric sulphide. From the weight of mercuric sulphide, two parts
** Pharm. J., 1906, vol. 77, p. 49.
** Proc. A. Ph. A., 1906, vol. 54, p. 439.
* Proc. A. Ph. A., 1906, vol. 54, p. 337.
* Proc. A. Ph. A., 1906, vol. 54, p. 414.
* Apoth, Zig, 1906, vol. 21, p. 686.
11
of which correspond to 4.42 parts of C11 H.N.O. (NO3)2Pig, the
amount of the double compound of caffeine and mercuric nitrate is
calculated and deducted from the weight of the crude caffeine. The
extraction of caffeine by chloroform is quite complete because of the
use of potassium nitrate.
P. Waentigºs discusses the estimation of caffeine in coffee. He
criticises the methods of Hilger and Juckensack, Katz and C. C.
Keller. Waentig demonstrated that the use of lead hydroxide in the
method of Katz does not cause decomposition of caffeine. He recom-
mends the substitution of carbon tetrachloride for chloroform in the
extraction of caffeine. Replying to the criticism of Waentig, C. C.
|\eller * states that the method was recommended for the estimation
of caffeine in tea, and should, of course, not be used for the estimation
of caffeine in goffee.
Carl Wolff " publishes a simplified method for the estimation
of caffeine in coffee. In conclusion, Wolff cautions that the substance
cxtracted by ethyl acetate, or by chloroform, must not be considered
to be pure caffeine. Instead, its nitrogen content must be determined
and the caffeine calculated therefrom. H. C. Lythgoe " has also pub-
lished experiments relative to the estimation of caffeine in coffee.
Colchicum. To eliminate the errors contained in a method
previously published, Panchaud “ has determined the solubility of
colohicine in mixtures of chloroform, ether and petroleum-ether. He
finds that petroleum-ether having a boiling point of 50 to 60 degrees
must be used in the assay and the ether must be completely dehy-
drated over metallic sodium. For the estimation of colchicine he
directs that 15 gms, coarsely powdered colchicum seeds be treated in a
flask with 150 gms. chloroform, the mixture shaken frequently during
thirty minutes, then 6 cc. 10 per cent, ammonia water added and the
mixture shaken thoroughly. After occasional shaking during one-half
hour, 100 gms. are to be filtered off through a plain filter of 20 cm.
diameter into a 200 cc. Erlenmeyer flask, the funnel being kept cov-
ered. The solution is distilled to complete dryness and the residue
dissolved in ong gm, dry chloroform, one gm. dry ether added, and
49 Pharm. Ceritralh., 1906, Vol. 48, p. 859.
50 Chem. Cenºîlbl., 1906, 2, 566, from Z. f. Öffentl. Chem., 12, 186.
51 U. S. Dept.' of Agricult., Bul. 99 (J. Am. Chem. Soc., 1906, 28 R., 512). "
52 Schweiz. Wochenschr. f. Chem. u. I’harm., 1906, 564; Pharm. Centrl.h.,
1907, vol. 48, p. 75.
48 Pharnh. # 1906, vol. 47, p. S10.
12
then 30 gms, dry petroleum-ether. The liquid and precipitate is trans-
ferred to a plain filter of 8 cm. diameter, using further petroleum-
ether to complete the transfer. The funnel containing the precipitate
is placed on an empty flask and the precipitate dissolved with warm
chloroform, care being taken that it is completely dissolved by wash-
ing the edge of the filter with chloroform. The chloroformic solution
is distilled and the residue dissolved in 15 drops of chloroform, 2 gms.
absolute ether added and, after solution, 30 cc. dry petroleum-ether.
The liquid and precipitate is poured on a tared, plain filter of 8 cm.
diameter. Floccules adhering to the flask are dissolved in 5 drops of
chloroform, one gm. ether added and then 10 gms, dry petroleum-
ether; the mixture transferred to the first filter and the precipitate
washed with a little petroleum-ether. The weight of the precipitate,
plus .0022 gm. (correction for solubility of colchicine in the quantity
of solvent used), multiplied by 10, furnishes the colchicine content
of the drug.
Fromme * reports that the better grades of colchicum seeds con-
tain 0.696 to 0.901 per cent. colchicine. -
Colombo. J. Gadamer “ and E. Günzel " have studied the
alkaloid content in colombo, and the latter has made some attempt
to determine its amount.
Conium. The A. Ph. A. Committee on the U. S. Pharmaco-
poeia " and the A. Ph. A. Committee on Drug Adulteration *" have
reported on the alkaloidal content of conium.
Ergot. While not analytical in character, considerable work of
great importance has been done during the past year in regard to the
question as to whether or not the activity of ergot is due to an alka-
loid and whether, therefore, the valuation of ergot may be based on
its alkaloid content. E. Vahlen "º concludes that the specific ergot
action is due to a principle which he calls clavin and which, while it
contains nitrogen, is neutral, not alkaloidal in character, and readily
soluble in water. The process for the manufacture of this product
has even been patented by him *, A very extensive examination of
Caesar & Loretz, Geschäfts-Bericht, 1906, p. 52.
Arch. der Pharm., 1906, 244, 255.
Arch deſ: Pharm., 1906, 244, 257.
Proc. A. Ph. A., 1906, vol. 54, p. 337.
Proc. A. Ph. A., 1906, vol. 54, p. 376.
Arch. f. exp. Pathol. u. Pharmak., 55, 131 ; Chem. Centrlbl., 1906, 2, 690.
Chem. Centrlbl., 1906, 2, 1896. .
:
:
i;
i
ū
13
the constituents of ergot has been made by F. Kraft". Kraft con-
cludes that ergot contains two alkaloids—one the crystallized ergot-
inin of Tanret and an amorphous alkaloid. He finds that the specific
action of ergot is not due to these alkaloids, but that other objection-
able properties of the drug are due to them. In conclusion, he states
that, the specific action of ergot must be due to a water soluble sub-
stance which cannot be shaken out with ether and which is neither a
base, an acid nor a phenol, and he is inclined to accept the work of
Vahlen according to which clavin is the essential constituent of ergot.
These conclusions, however, are not accepted by G. Barger and H. H.
Dale * who, working in the Wellcome Research Laboratories, have
also investigated ergot most thoroughly. They believe to have
proven that the specific action of ergot is due to the amorphous alka-
loid which they call ergotoxin.
Gelsemium. L. E. Sayre * reports Some experiments on the
estimation of the alkaloidal constituents of gelsemium.
Guarana. See Coffee.
Hydrastis. Georg Heyl "º discusses the alkaloidal content of
fluidextract hydrastis. He examined a considerable number of speci-
mens prepared by druggists and also by pharmaceutical manufactur-
ers. He also gives the hydrastine content found by a large number of
investigators—from all of which he concludes that a requirement of
2 per cent. of hydrastine for the fluidextract is not excessive. For
the estimation of hydrastine he uses the following method: 7.5 gm.
fluidextract are concentrated to a thick extract in an Erlenmeyer
flask. The residue is dissolved in 10 cc. water, and then 10 gms. petro-
leum benzin and 50 gms. ether added, the flask stoppered, rotated and
then 2.5 gms. 10 per cent. ammonia water added. The mixture is
Shaken frequently during one hour and then transferred to a sepa-
rator having a capacity of 250 cc. After separation has occurred, the
aqueous fluid is drawn off. The benzin-ether solution passed through
a pledget of fat-free cotton into a dry Erlenmeyer flask and the flask
stoppered. 50 gms. Of this solution is weighed by difference into a
separator and extracted with 10 cc. of a mixture of one part hydro-
90 Arch. d. Pharm., 1906, wol. 244, p. 336.
* Arch. d. Pharm., 1906, vol. 244, p.
* Proc. A. Ph. A., 1906, vol. 54, p. 383.
* Apoth. Ztg., 1906, vol. 21, p. 797.
14
chloric acid and four parts water, with two further portions of water
5 cc. each containing a few drops of dilute hydrochloric acid, and
finally with 5 cc. water. To the acid extractions is added 50 gms.
ether, 2.5 gms. ammonia water, and the mixture shaken thoroughly
and frequently. After one hour the fluid is transferred to a separator,
the watery solution drawn off and the ether filtered through a small
plaited filter, the funnel being kept covered. 50 gms. of the filtrate
are transferred into a tared vessel, the ether allowed to evaporate
spontaneously and the residue dried at 105 degrees. As a precaution,
Heyl carried out all these operations as quickly as possible although
he has never observed the crystallization of hydrastine from the ether
solution reported by other investigators. The work of Heyl has been
criticised by A. W. van der Haar", who considers the method of
Linde—a modification of which Heyl adopted—antiquated. He pre-
ſers the method of Rusting-Smeets, carried out as follows: 10 gms. of
extract are mixed in a capacious tared vessel with 20 cc. water and
the contents reduced by evaporation to from 10 to 11 gms. Then 1.5
ce. 12.5 per cent. hydrochloric acid are added and after cooling suffi-
cient water to make 20 gms. Now 0.5gm. infusorial earth is added, the
mixture well shaken, filtered and 10 gm, transferred to a 100 cc. vial.
To this 4 cc. 10 per cent, ammonia water and 25 cc. ether are added,
and after thorough shaking for a few minutes 25 cc. petroleum-ether,
hoiling at 50 to 75 degrees. After again agitating, 1.5 powdered
tragacanth are added, the mixture shaken vigorously, 40 cc. of the
clear liquid transferred to a tared flask, and the contents reduced
to 10 to 11 gms. The flask is stoppered and kept in a cool place for
several hours. Then the liquid is carefully poured off, the crystals
washed with a little petroleum-ether, dried on a water bath and
weighed. - - -
In replying to this criticism, Heyl" states that he was familiar
with the Rusting-Smeets' method, but that he, nevertheless, adopted
the method of Linde. -
The alkaloidal strength of hydrastis has been taken up by the
A. Ph. A. Committee on Drug Adulteration "", also by the A. Ph. A.
Committee on the U. S. Pharmacopoeia".
* Apoth. Żtg., 1906, vol. 21, p. 1050,
* Apoth. Ztg., 1906, vol. 21, p. 1060.
* Proc. A. Ph. A., 1906, Vol. 54, p. 338.
"7 Proc. A. Ph. A., 1006, vol. 54, p. 439.
15
Hyoscyamus. See Belladonna.
Ipecac. H. M. Gordin" directs 5 gm. ipecac, No. 60 powder,
to be shaken for one hour with 2.5 cc. 10 per cent. sodium carbonate
solution and 25 cc. of ether-chloroform (ether, 3 volumes and chloro-
form, 1 volume) and then percolated to exhaustion with chloroform-
ether. The percolate is shaken out with very dilute sulphuric acid,
sodium hydroxide added in excess and the liquid extracted with ether-
chloroform. The assay is then finished as directed above for aconite
- A. B. Lyons" believes that the valuation of the fluid extract of
ipecac should be based on titration with Mayer's reagent.
Reports on the alkaloid content of ipecac are made by the A. Ph.
A. Committee on Drug Adulteration " and also by the A. Ph. A.
Committee on the U. S. Pharmacopoeia". -
Rola. See Coffee.
Nux Vomica. J. M. Francis “ considers the method of the
U. S. P. VIII a poor substitute for the one abolished. He believes
the process of determining strychnine by oxidation was tried out and
condemned years ago. On the other hand, E. H. Farr and R. Wright”
have experimented with the method and conclude that the process, if
worked carefully, gives accurate results. The details which they pro-
pose differ from the directions of the Pharmacopoeia in that the sul-
phuric acid solution of the alkaloids is raised to a temperature of 50
degrees before the nitric acid is added. H. M. Webster and R. C.
Pursel “ have also studied the method. . They record their own ex-
periments as well as those of others to show that the process is ex-
ceedingly liable to give variable results. In one series of experiments
they show that, if the nitric acid mixture is allowed to trickle down
the side of the beaker containing a solution of brucine in sulphuric
acid so as to have a separate layer at the bottom, then at the end of
30 Seconds this layer becomes pink, then gradually red, and if the
mixture at the end of two minutes is rotated, a bright red solution
results giving no reactions for alkaloids at the end of 10 minutes.
* Proc. A. Ph. A., 1906, vol. 54, p. 879.
* Proc. A. Ph. A., 1906, vol. 54, p. 440.
79 Proc. A. Ph. A., 1906, vol. 21, p. 339.
ps . A. Ph. A., 1906, vol. 21, p. 440.
*1 Proc
Ph; A., 1906, vol. 24, p. 453.
72 Proc. A. Ph.
Tº Pharm. J., 1906, vol. 77, p. 83
74 Am. Drug., 1906, vol. 49, p. #62.
*r-
16
*
If, on the other hand, the brucine solution is rotated while adding the
nitric acid, then a water-white mixture results which, at the end of
24 hours, only has a faint yellow tinge and still contains 91 per cent.
of the brucine. If the nitric acid is added in a haphazard manner
and the beaker rotated as directed in the official method, then exceed-
ingly variable results are obtained. From further experiments they
finally conclude that the success of the method depends on the pres-
ence or the formation of lower oxides of nitrogen in the nitric acid.
As the result of their experiments they propose the following modifi-
cation of the U. S. P. text: “Dissolve the alkaloidal residue in 15 cc.
of 3 per cent, sulphuric acid. To this solution add 3 cc. of the mix-
ture of equal volumes of nitric acid, specific gravity 1.4, and distilled
water, then add 1 cc. of a 5 per cent. Solution of sodium nitrite in
water and after rotating the liquid a few times set it aside for exactly
30 minutes, stirring it gently three times during this interval * The
Solution is then made alkaline in the usual way.
G. Fromme * notes that in the available literature no reference
is made to the difference between volumetric and gravimetric valua-
tions of nux vomica. Thus, one and the same specimen of nux vomica
showed 3.80 per cent. by titration according to the method of the
German Pharmacopoeia (according to which the alkaloid is extracted
by digestion of the drug with ether, chloroform and sodium hydroxide
solution, and after decanting the ether-chloroform solution and re-
ducing it to one-half by distillation, agitating it with the stated
volume of one-tenth normal hydrochloric acid and determining the
excess of acid used), the method of Keller, when the alkaloidal resi-
duc was weighed, indicated 3.39 per cent., while it indicated 2.71 per
cent, when the alkaloidal residue was titrated. A large number of
experiments are recorded which were made in an attempt to learn the
cause of these wide variations in the results. The experiments show
that the method of the German Pharmacopoeia, even with modifica-
tions, gives excessive results, and that these high results are due to the
fact that in the digestion of the drug with chloroform, ether and
sodium hydroxide, soap is produced, carried over into the ethereal
solution and in the estimation determined as alkaloid. The gravi-
metric estimation, based on the Keller method, gives higher results
than if this alkaloidal residue is titrated, because of the introduction
7° Geschäfts Bericht, Caesar & Loretz, 1906, p. 58.
17
of impurities. Low results, which at times are obtained, are due to
the partial decomposition of the alkaloids when they are dried at a
high temperature. Experiments were made to remove all fat from
the drug prior to the assay so as to avoid the error introduced through
the formation of soap. The complete removal of fats, however, is so
difficult that it is not feasible. Another source of error is due to the
solubility of brucine chloride in chloroform. Fromme believes that
for the determination of total alkaloids in nux vomica the drug, with-
out previous removal of fat, should be extracted with a mixture of
chloroform, other and ammonium, not sodium, hydroxide, and that
the ethereal solution so obtained should be distilled to dryness at
a low temperature, the residue dissolved in chloroform, treated with
ether, water, iodeosin and titrated, or else it should be extracted with
dilute acid and the alkaloids, after making alkaline, extracted from
this with chloroform, and determined gravimetrically.
The official standard for nux vomica is discussed by the A. Ph. A.
Committee on Drug Adulteration” and also the A. Ph. A. Committee
on U. S. Pharmacopoeia". E. H. Farr and R. Wright "º discuss the
alkaloidal content of nux vomica and extract of nux vomica, especially
as to the relative amounts of strychnine and brucine. Since brucine
is not inert, but possesses properties similar to those of strychnine,
though weaker, they believe that the brucine content should not be
neglected, but instead should be calculated into terms of strychnine
and the strychnine standard established on this dual basis.
Opium. Most valuable work on the estimation of alkaloids is
done by a subcommittee under the direction of the Association of
Official Agricultural Chemists with L. F. Kebler as referee. At the
22nd annual convention of this Association (Bulletin No. 99, U. S.
Department of Agriculture, Bureau of Chemistry, page 61) co-opera-
tive work on the assay of opium was reported. A specimen of pow-
dered opium was sent to chemists who offered to co-operate, with
directions to assay it by the method of the U. S. P. 8th Revision, with
additions; by the U. S. P. method as modified by Lamar; by the
U. S. P. method as modified by Dollme; and by the Stevens' method.
The results cannot well be abstracted, but should do a great deal to-
Proc. A. Ph. A., 1906, vol. 54, p. 340.
Proc. A. Ph. A., 1906, vol. 54, p. 440.
Pharm. J., 1906, vol. 77, p. 94.
7
7
7
S
18
wards putting the assay of opium on a more scientific basis. As a
result of the work the referee recommended “that the method
recognized by the present Pharmacopoeia, 8th Revision, for the assay-
ing of opium be adopted as a provisional method by the Association
of Official Agricultural Chemists.”
The official method of estimating morphine in opium has
been criticised by A. B. Lyons ". Especially pertiment is the caution
to provide against the absorption of carbon dioxide from the
air in determining the solubility of the morphine in lime water.
Lyons notes that he has used with much satisfaction the Liquor
Calcis Saccharatus of the British Pharmacopoeia in place of lime
water. P. Ascher * proposes several modifications of the method of
.A. B. Stevens. Having found that opium contains salts of ammonium,
he made experiments from which he concluded that this interferes
with the estimation of morphine in that the complete solution of
morphine by the treatment with lime is prevented. He therefore
directs that to expel ammonium the opium be treated with a solution
of potassium hydroxide and then evaporated to dryness prior to the
solution of the morphine by calcium hydroxide and water. Besides
recommending other minor changes, he gives his experience with the
official hematoxylin solution. Instead of recommending the use of an
old solution he proſers a solution prepared by boiling for some time a
little hematoxylin dissolved in water.
A comparison of the results obtained in the valuation of tincture
of opium, when estimated according to the methods of the 7th and
Sth revision of the U. S. Pharmacopoeia, has been made by T. E.
Wetterstroem ‘’’. G. Bergström ** ſinds that while continuous shaking
facilitates the separation of morphine, the separation is not complete
at the end of 10 minutes, and that even after 24 hours further separa-
tion of morphine takes place. To obtain concordant results, a definite
time must be set for the separation of morphine. If the time allowed
is too great, separation of calcium meconate is liable to give excessive
results. He considers the substitution of ethyl acetate as advantage-
ous, but cautions against the use of water saturated with it. While it
has been claimed that the presence of narcotine does not interfere
79 Proc. A. Ph. A., 1906, vol. 54, p. 441 and 445.
$9 Am. J. Pharm., 1906, vol. 78, p. 262.
* I*roc. A. I’h. A., 1906, vol. 54, p. 431.
83 Svensk Farm, Tidskr., 1905, Nos. 19 and 20 ; from L'harm. Centrl.h., 1906,
Yol. 47, p. 632.
19
with the titration of morphine when iodeosin is used as indicator,
Bernström finds that in the presence of marcotine high titration
results are obtained because the indicator is not entirely indifferent
to it. G. Fromme 83 reviews the work of Bergström and criticises
Some of his conclusions. Fromme does not agree to the recommenda-
tion that 24 hours should be permitted for the complete separation of
morphine, nor to the recommendation to accept the volumetric esti-
mation and use the gravimetric determination as a control only. As
one source of difference between these two estimations, he notes that
morphine is rendered anhydrous only by long continued drying at
100 degrees.
II. M. Gordin * has studied the separation of morphine from
solutions containing glycerin. After trying various methods, he
adopts a method based on the precipitation of morphine by iodine
solution, decomposition of the morphine periodide by sulphurous acid
and precipitation of the free alkaloid by potassium carbonate.
Georges and Gascard ” base a colorimetric determination of
morphine on the tint produced in a neutral or very faintly acid solu-
tion of morphine by iodic acid with subsequent addition of ammonia.
For comparison, a standard solution of morphine hydrochloride is
used. C. Mai and C. Rath * recount their experiments in the colori-
metric estimation of small quantities of morphine by the use of iodic
acid, Froehde's reagent, and formaldehyde-Sulphuric acid. They give
preference to the latter reagent.
Physostigma. Having found the pharmacopoeial assay method
for extract of physostigma to be rather complicated, H. M. Gordin *
has devised two methods which are recommended because they are
expeditious.
Pilocarpus. For the valuation of fluid extract of pilocarpus,
H. M. Gordin * directs the fluidextract to be rendered strongly alka-
line and then extracted in a specially constructed separator “No. 1”
(see Apparatus) with a mixture of three volumes of ether and one
Volume chloroform. The ether-chloroform solution contained in
* Geschäfts-Bericht Caesar & Loretz, 1906, p. 48,
** Proc. A. Ph., A., 1906, vol. 54, p. 374.
Sº J. Pharm. Chim., 1906, vol. 23, p. 513.
* Arch. der Pharm., 1906, vol. 244, p. 300.
$7 Proc. A. Ph. A., 1906, vol. 54, p. 381.
** Proc. A. Ph. A., 1906, vol. 54, p. 380.
S” I’roc. Mo. Pharm. Assn., 1906, p. 104,
20
Separator “No. 2” is concentrated to expel any ammonia present,
diluted with ether and extracted with standard acid. The excess of
acid is titrated in the usual way. *
The alkaloidal strength of pilocarpus has been discussed by C. E.
Casparis?, the A. Ph. A. Committee on Drug Adulteration" and the
A. Ph. A. Committee on U. S. Phrarmacopoeia "". While Caspari
found eight out of ten specimens to contain less than 2 per cent of
alkaloids, the report of Francis and others would indicate that a drug
meeting the official standard is readily obtained. A. B. Lyons cor-
rectly comments that “there is pilocarpus and pilocarpus.”
Stram onium See Belladonna.
Veratrum. G. Bredemann “” has published an exhaustive in-
vestigation on the estimation of alkaloids in veratrum album and pro-
poses the following method: 12 gms. powdered drug are rotated with
120 cc. of a mixture of equal parts of chloroform and ether, then
10 cc. sodium hydroxide solution is added and the mixture shaken
frequently during three hours; then sufficient water is added to cause
coherence of the drug. The ether-chloroform solution, always more
or less turbid, is decanted as completely as possible, shaken with mag-
nesium oxide and three or four drops of water, and then the liquid
poured through a dry filter and 100 cc. of the transparent filtrate,
corresponding to 10 gms. drug, collected. The chloroform-ether solu-
tion is extracted three times with 20 cc. of water containing acetic
acid. The united acetic acid extractions are made alkaline with
sodium hydroxide and extracted three times with a mixture of equal
parts of chloroform and ether. The ether-chloroform solution is
driven off, the alkaloidal residue dried at 100 cc, and weighed. For
the estimation of alkaloid in the tincture it is proposed that 100 gms.
tincture be concentrated to one-half its volume on a water bath. Then
1 gm. paraffin and about 25 cc. water are added, and the liquid warmed
until all alcohol has been expelled. To the warm liquid 2 gm. acetic
acid are added and the liquid allowed to cool with frequent stirring.
It is then filtered into a separator through a small wet filter. The
paraffin and oil which remain on the filter are heated on a water bath
with 20 cc. water and 1 gm. acetic acid until the paraffin melts. The
90 Proc. A. Ph. A., 1906, Vol. 54, p. 431. -
91 Proc. A. Ph. A., 1906, vol. 54, p. 440.
* Apoth. Ztg., 1906, vol. 21, p. 41, 53.
tº
21
liquid is then allowed to cool, passed through the filter first used and
the dish and filter washed thoroughly with water. The united filtrates
are made alkaline with sodium hydroxide and extracted with 20, 10
and 10 cc. chloroform. Besides estimating the alkaloids gravimetri-
cally, the author also attempted to work out a volumetric estimation.
Since the drug has been shown to contain 4 alkaloids he proposes that
the average molecular weight of these be taken for the calculation
of the ce. equivalent. The correctness of this the author believes to
have demonstrated by preparing the pure alkaloids and determining
their neutralization equivalent. The alkaloidal content of the speci-
mens of the drug which were examined varied from 199 to .933
per cent. &
MONOGRAPHS
1. Popular German Names. This popular pamphlet has been revised
2.
twice by its author, Dr. Fr. Hoffmann. 0.50
Reagents and Reactions known by the names of their authors.
Based on the original collection of A. Schneider; revised and en-
larged by Dr. Julius Altsch ul; translated from the German by Dr.
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*

Plant Pigments
*
By
I. W. BRANDEL
With a preface by the author of the series
MILWAUKEE
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, - 1908
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MILWAUKEE
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1908
Plant Pigments
By
I. W. BRANDEL
With a preface by the author of the series
MILWAUKEE
Pharmaceutical Review Publishing Co.
1908
P R E F A 0 E.
In May, 1901, the author of this monograph isolated thymoqui-
none from the non-phenol constituents of the oil of Monarda fistulosa. 1
In his report of this discovery, the writer made the following state-
ments:
“This appears to be the first instance in which thymoquinone has been
isolated. . . . from a volatile oil.” The relationship of thymoquinone to two
other constituents, viz. cymene and carvacrol, also to hydrothymoquinone
was pointed out. “The question of thymoquinone in this oil, however,
seems to be of greater significance. The question of the color of the oils is
. One that has received but scant attention. . . . . . “If the plant can oxidize
either carvacrol or thymol to hydrothymoquinone . . . . it does not appear
difficult to explain the production of dark colored oils. . . . . ’’ ‘‘Under favor-
ablé conditions the thymoquinone” (formed possibly by autoxidation) “and
the hydrothy moduinone can then combine to form the intensely colored
quinhydrone.”
Only a few days after this report had appeared, the author
succeeded in isolating hydrothymoquinone from the phenol constit-
uents of the same oil.” The isolation of these two substances opened
up not only a new chapter in the investigation of volatile oils,
particularly of their color, but threw a flood of light on the possible
chemical composition of numerous plant pigments, their oft times
peculiar, unstable behavior, the numerous shades and even total
differences of color that are produced by simple chemical changes,
the rather sudden appearance of fall coloration of leaves and the
causes of subsequent, almost equally rapid changes.
The laboratory investigations that have grown out of this dis-
covery have already been reported. 3 Some of them appear to have
1 Ph. Rev., 19, p. 200.
2 Ibidem, p. 244.
S Thymoquinone in wild bergamot oil. Ph. Rev., 19, p. 200.
Hydrothymoquinone in wild bergom ot oil. Ibidem, 19, p. 244.
Aſ 1.4 Terpadiene-6-oxime-3-one (Nitrosothy mol). Ph. Arch., 4, p. 107.
Notes on rare Monarda, oils. Ph. Rev., 21, p. 109.
The volatile oil of Monarda citriodora. Ibidem, 22, p. 153.
Oxydase from Monarda, fistulosa (F. R.). do., 22, p. 190.
The thermal death points of the Monarda ferments (D. B. S.) do., p. 193.
A 1.4 Terpadiene-3-oxime–6–one (Nitrosocarvaerol) do., pp. 248 & 290.
no direct bearing on the subject of plant pigmentation. While no
good reason existed for republishing these experimental data, there
appeared to be a special need of a chemical monograph on the entire
subject in which the subject matter might be treated in accordance
with modern ideas of chemical structure and classification.
The original idea, merely to take up the quinhydrone hypothesis
of plant pigmentation, was abandoned because such a treatment of
the subject matter would emphasize artificial lines of distinction that
should be obliterated rather than exaggerated. The additive capa-
city of pigment producing compounds, which structural chemists
indicate by the use of the C=O group in the writing of graphical
formulas, is not peculiar to those ketones which are designated
quinones and which they manifest in the formation of the highly
colored phenoquinones and quinhydrones, but is found in the xanth-
ones, flavones, etc., some of the best known and most widely
distributed plant pigments or pigment producers. The same group-
ing of elements is also found in the alizarin group of plant pigments
of which a representative was isolated from Monarda fistulosa,
thirteen years ago in the writer’s laboratory.4 Indeed, the ease with
which certain basal substances can be made to yield pigments of
different classes, seemed to exclude any one sided treatment. Such
is the excuse — if any need be made — for the growth of a mono-
graph on plant pigments from the isolation of a single constituent
from a volatile oil.
Reference to the experimental work of the author will be made
in the same manner as the work of other investigators is referred to.
4 Pharm. Itund , 13, p. 208.
Plan t Pig m ent S.
By 1. W. Brandel
Like the “Riechstoff” (odoriferous principle), the “Farbstoff.”
(coloring principle) has played an important role in the history of
phytochemistry Whereas with the isolation and study of the vola-
tile oils, the former resolved itself relatively early into numerous
chemical individuals, such as camphor, thymol, menthol, etc., the
latter defied analysis much longer and in one form or another the
red, blue or yellow “Farbstoff” will be found as a spook in phyto-
chemical and in plant physiological literature throughout the 19th
century.
This being the case, it is noteworthy to record that as early as
1793, Gren fails to enumerate plant pigments as a special class of
proximate constituents of plants.” Although a few years later Hermb-
-staedt adds several other classes to the list of proximate plant
constituents, he also omits intentionally the pigments, commenting
on this omission in the following words: — “Dass der Farbestoff,
sowie der Riechstoff, welche man noch vor kurzem als eigene Be-
stand theile der Pflanzen anzuerkennen pflegte, nicht ferner als solehe
angesehen werden können, wird fernerhin gezeigt werden.” ”
With the isolation of pigments, especially of such substances
which could be used as dyestuffs, the notion of a “Farbstoff” was
forever removed from strictly chemical consideration, but in its
stead “Pflanzenfarben”, or better still “Farbstoffe”, pigments, had
to find a place in the classification of proximate constituents of
plants.
Following the lead of inorganic chemistry which had adopted the
classification of derivatives of the elements into acids, bases and
salts, organic chemistry which in its early stages of development
was largely plant chemistry, classified the proximate constituents of
plants into acid, basic (the alkaloids) and indifferent.8 In this
classification, the “Pflanzenfarben” (note the word, plant colors)
rather than “Pflanzenfarbstoffe” or plant pigments) were placed
1 Gren : Grundriss der Naturlehre (1793), p. 319; also Gren: Handb. der ge-
samten Chemie. Zweiter Theil (1794), p. 3.
2 Hermbstaedt: Grundriss, d. allgem. Experimental Chem. (1 SO5), Bol. 4, p. 38.
3 Berzelius: Lehrbuch d. Chemie, Iłól. 6 (1837), p. 107.
2
among those indifferent substances that were devoid of sufficient
characteristics to define them chemically. 4
Somewhat later when organic chemistry was defined as the
chemistry of complex radicles, the known organic substances were
classified 1) into those containing acid-forming radicles; 2) those
containing base-forming radicles (the alkyl radicles, not the alka-
loids); and 3) into those the radicles of which were still unknown.
Fats, volatile oils, alkaloids etc., also the “Farbstoffe” (note the
change from Berzelius’ word ‘Pflanzenfarben’) were considered in a
supplement, the lumber chamber as it were of organic chemistry. 5
In the course of time, the chemical structure of some of the
colored constituents of plants became known. This knowledge enabled
their proper classification and removal from the lumber chamber, to
which, however, numerous other substances were added even more freely.
Such has been the condition of chemical literature pertaining to
plant pigments for the past half century." During this period the
interest taken in plant pigments by organic chemists has been
greatly overshadowed by the zeal which they displayed in the
production of artifical dyestuffs. With the development of this
chapter of organic and industrial chemistry, great progress in the
advancement of our knowledge of colored substances has been made
in which the chemistry of plant pigments as a whole has not shared.
Aside from the theories on dyeing, which are by no means without
application to the study of plant pigmentation, the theory of
chromophorous groups is possibly one of the most important results
of general study in this field. 7
While the writer is by no means inclined to subscribe to the
theory of chromophorous groups in its narrower application, but
believes that the color of a substance is a function of the structure
of the entire molecule, it must be admitted that this theory is of
use outside of the field of synthesis of new artificial dyestuffs.
The classification of artificial dyestuffs as adopted by writers on
this subject is of little or no use to the phytochemical student. Of
the following list 8 only those marked by an asterick, namely hydroxy-
Quinones, hydroxyketones, Xanthones, flavones, cumarines and indigo
dyestuffs, have known representatives in plants. g
See Berzelius' description : Ibidenn, Bd. 7, p. 123. &
jºung. Pp. vii. xiv.
Nietzki: Chemie der Organischen Stoffe, 4th edition
List according to Nietzki: Chemie der Organischen Farbstoffe, 4th edition.
:
Chromophorous group.
Nitro derivatives
—NO2
Azo derivatives —N=N–
Hydrazone and pyrazolone derivatives =C=N–NHC6H5
Azomethine and stilbene derivatives —C-N– and –C–C–
H H. H.
Hydroxyquinones” and quinone oximes =C=O
* Hydroxyketones,” Xanthones”
Flavones” and Cumarines”
Diphenylmethane derivatives Ce Hä–C–C6H5
|
Triphenylmethane derivatives (C6H5)2=C–C6H5
|
Quinone imides
2. -N _2=c Or” 2. -N =2.
Quinoline and Acridine derivatives
/~
ThiOzol derivatives
/S N
—C C—
i f
—C f
NN/
Indigo dyestuffs"
HC–CH
| |
HC CH
N/
N
H
The general survey of plant pigments and dyestuffs of known
constitution - obtained from plants, which follows, is based on the
definition of organic chemistry best adapted for purposes of classi-
fication, viz. that it is the chemistry of the hydrocarbons and their
substitution products.
By arranging the plant pigments of known constitution accord-
ing to their degrees of saturation, calculated from the hydrocarbons
underlying the compounds which contain a chromophorous group,
representatives were found under the formulas of saturation
CnH2n-4 to CnH2n-82, also CnH2n-36.
All the compounds, important as plant pigments, which are not
quinones, can be placed under three of these formulae of saturation,
viz. CnH2n-8, CnH2n-14 and CnH2n-16. Quinones of these degrees
of saturation are also known.
4
Degrees of Saturation.
CnH2n-4.
The hydroquinones constitute a group of di-atomic phenols, in
which the two hydroxy groups are in para position. The quinones
par excellence are products of oxidation of the hydroquinones and
have two ketone groups in the same position,
The additive capacity of these diketones, indicated in the
structural formula by the two carbonyl groups (C=O), manifests
itself readily toward substituted water molecules of the phenol type.
H
In like manner as e. g. chloral cClºck readily adds the elements of
()
H
alcohol to form chloral alcoholate CCl30–OH so the quinones add
N. :
OC2H5
on the elements of those tertiary alcohols known as phenols. Being
twice unsaturated, as indicated by two C=O groups in the formula,
they can add on the elements of two molecules of a monatomic
phenol or the elements of one molecule of a diatomic phenol. The
former class of addition products are known as phenoquinones.
O— —II—OC6H5 OH
/ + /
'— C—OC6H5
/N
- || ||
| H
N / H—OC6H5 Nvº
C— C—OC6H5
N +
O— OH
Quinone + 2 mol. monatomic phenol - Phenoquinone.
O— —H OH
< —OC & O C
ſh. On ºn O.
+
` D./ `º (T) NSº
o— —H `oh

Quinone + 1 mol. diatomic phenol 2- Quinhydrome.
5
Like the chloral alcoholate these alcoholic addition products are
unstable being broken up e. g. by a number of indifferent organic
solvents as the alcohol from chloral alcoholate is Set free by water.
Whether, like water in the case of the chloral, these organic solvents
unite with the quinone to form definite chemical — though loosely
bound — compounds, has not yet heen ascertained.
Both classes of addition products are characterized by hydroxy
groups, the hydrogen atoms of which are readily replaceable by
positive elements or groups.
The hydrobenzoquinone and its corresponding quinone and quin-
hydrone have been known for a long time. Woskresensky 1 in 1838
isolated, by the action of maganese dioxide and sulphuric acid on
quinic acid, a compound which he termed ‘clinoyl’. He did not
further study this compound and it was not until 1843 that Got-
lieb 2 again took up the work. The latter obtained from quinic acid
a substance which, when mixed with Woskresensky’s ‘chinoyl', formed
a compound of a beautiful green color. This is undoubtedly the
earliest formation of a quinhydrone although the nature of the
compound was neither studied nor understood at that time.
Woehler 8 in 1844 was the first to make a systematic study of
these interesting compounds. The term chinoyl, he changed to
quinone because he considered the compound analogous to acetone.
The reduction product of this compound he termed “colorless hydro-
quinone” and the green substance obtained by Gotlieb, was called
“green hydroquinone”. He suggested that this consisted of a mole-
cule of quinone and a molecule of colorless hydroquinone, but it was
a disputed question for a long time whether the “green hydroquinone”
contained one or two molecules of the true hydroquinone with one
of the quinone. Lieberman 4 finally proved conclusively that the
Quinone and hydroquinone would unite only in the proportions of
one molecule of each. Graebe 5 seems to have been the first to
designate this “green hydroquinone” by the word quinhydrone, but
he says nothing as to the origin of the word. Although the empiri-
cal character of the quinhydrone was definitely settled by Lieberman
in 1882, its structure as conceived at present was first proposed by
Jackson and Grindley 6 in 1895.
Ann. d. Chem., 27, p. 298.
Ann. d. Chem., 45, p. 354.
Ann. d. Chem., 51, p. 145.
Ber. 12, p. 1500.
Ann. d. Chem., 146, p. 36.
Am. Chem. Journ., 17, p. 587.
:
6
Since the time of Woehler’s work, a considerable number of
quinones of this as well as of other degrees of saturation and their
corresponding hydroquinones have been prepared. The specific terms
Quinone, hydroquinone and quinhydrone, originally applied to the
first members of the respective series, are now applied generically to
the three classes of compounds. The initial quinone of the benzene
series is now also called benzoquinoné and its corresponding hydro-
Quinone benzohydroquinone, the quinhydrone, benzoquinhydrone.
Although thirteen hydroquinones of the benzene series and their
corresponding quinones are known, only three quinhydrones have
been well characterized. These are benzoquinhydrone, toluguin-
hydrone and thymoquinhydrone. It seems rather strange that
although almost the first property to be noticed in the case of the
benzoquinone and benzohydroquinone was their tendency to unite
to form a colored quinhydrone, so few of the quinhydrones of the
other known hydroquinones and quinones have been prepared. That
such compounds can exist, is shown by the fact that in the reduc-
tion of many of the quinones to the hydroquinones or in the oxid-
ation of the hydroquinones to the quinones, colored liquids have
been obtained as intermediate products or as residues.
The hydroquinones of this degree of saturation are colorless
crystalline substances which are not volatile with water vapor,7 but
in some instances can be sublimed. The lower members are readily
soluble in hot or cold water while the higher members are almost
insoluble, even in hot water. They dissolve in caustic alkalies, the
solution rapidly turning red. The metallic derivatives of these com-
pounds have not been prepared. Lead acetate, which precipitates
an insoluble lead derivative with other di-atomicphenols, has no
effect when added to a solution of a hydroquinone. Ferric chloride
does not produce a blue solution as in the case of other di-atomic
phenols, but oxidizes the hydroquinone to its corresponding quinone.
The most characteristic property of the hydroquinones, as well as
the most important to the subject of plant pigmentation, is the
ease with which they can be oxidized to quinones. The presence of
the merest traces of impurities in the crystalline substance, or the
addition of some of the weakest Oxydizing agents may readily
change the hydroquinones to quinones.
The quinones, on the other hand, are crystalline substances of a
7 This, however, may not exclude their volatility with the vapor of other sub-
stances, such as phenols as e. g. in Monarda Oil.
7
light yellow color, having a peculiar “chlorine-like” odor.3 They
can be sublimed and are also very volatile with water vapor. They
are practically insoluble in water. The melting points of the
quinones are always lower than the melting points of the correspond-
ing hydroquinones. Just as the hydroquinones were easily oxidized
to quinones so the quinones can very readily be reduced to hydro-
quinones.
The changing of a quinone to a hydroquinone by a process of
auto-oxidation can be shown by the following experiment. If an
approximately 20 percent solution of thymoquinone in limonene or
pinene be allowed to stand, a part of the thymoquinone is changed
to hydrothymoquinone and some other compound. The hydrothy-
moquinone thus formed unites with the excess of thymoquinone to
form the thymoquinhydrone and the yellow solution turns red. As
more thymoquinhydrone is formed it crystallizes out from the red
solution. The purple thymoquinhydrone, if allowed to stand in con-
tact with the solution, gradually changes to the colorless hydro-
thymoquinone.
The hydroquinones and quinones unite very readily to form a
quinhydrone. They will unite to some extent by merely bringing
the crystalline substances together; also by allowing their mixed
ethereal solutions to evaporate.” The quinhydrones are highiy
colored crystalline substances, the color varying from the green of
the benzoquinhydrone to the purple of the thymoquinhydrone. They
are soluble in most organic solvents, ether, alcohol, benzol, etc.,
with which they form almost colorless or slightly yellow solutions.
Upon evaporation of these solutions, the colored quinhydrone is
again obtained. The merest trace of some of these solvents will
destroy the color of the quinhydrone. With such solvents as phenol,
carvacrol, water and pinene the quinhydrones form red-brown solu-
tions. Upon heating these solutions the color disappears, but returns
again upon cooling. By the careful addition of ammonia, these
solutions are turned blue.
By the replacement of one or more of the hydrogens, connected
to a cyclic carbon atom, by hydroxy groups, there is obtained from
the quinones, a series of hydroxy derivatives. These so-called
hydroxyquinones are important to plant pigmentation, in as much
8 Such at least is the rather unsatisfactory traditional description.
9 Ethereal solutions loose this property upon standing.
8
as they not only are in themselves colored, but form a second series
of quinhydrones, i. e. hydroxyquinhydrones with their corresponding
polyatomic phenols. The ethers of these hydroxyhydroquinones and
hydroxyquinones, unite to form a third series of quinhydrones.
The hydroxyhydroquinones of the benzene series, as well as their
ethers, are colorless crystalline substances which do not readily form
metallic derivatives and are very easily oxidized to compounds con-
taining two carbonyl groups in para position. The hydroxyhydro-
Quinone ethers in which the alkyl radicals replace one or both of
the hydroxy hydrogens of the original hydroquinone, are not here
considered since such compounds would no longer have free hydroxy
groups in para position and therefore do not forin quinhydrones.
The corresponding quinones of such compounds would also be im-
possible.
The hydroxyquinones are crystalline compounds, whose color
varies from a light yellow to a black, the color increasing with the
increase in the number of hydroxy groups. Thus, hydroxybenzo-
quinone is light yellow, not differing much from the color of the
simple benzoquinone. Dihydroxybenzoquinone is dark yellow, tri-
hydroxybenzoquinone, black the tetrahydroxy derivative is blue-
black. The hydroxyquinones readily form colored metallic derivatives,
the color of which varies from green to blue.
By the substitution of alkyl radicles for the hydrogen of the
hydroxy groups, forming ethers, the color of the resulting ethers
goes back to the original yellow of the simple quinones. If all the
hydroxy hydrogens are thus substituted by alkyl radicles, the com-
pound is yellow. If the substitution has taken place only in part,
the color of the resulting compound varies between yellow and the
color of the original hydroxyquinone.
These generalizations, while probably somewhat premature be-
cause of the relatively few data on which they are based, may never-
theless prove helpful because they seem to indicate general tendencies
in color changes. In the study of plant pigments, their importance
can scarcely be questioned.
Only a few hydroxyquinhydromes and their ethers have thus far
been prepared; and even in these cases the compounds have not
been well characterized, yet it is evident that they are highly colored
compounds which have in general the properties of the simple quin-
hydrones.
9
..' . The occurrence in plants of the compounds belonging to the
degree of saturation CnH2n-4, which have been positively identified
is restricted to a few representatives.
Thymoquinone as well as its corresponding hydroquinone have
been isolated and identified from the oils of several species of
Monarda. 10 The isolation of both of these compounds readily de-
monstrates that the red-brown color of all the Monarda oils, is, no
doubt, due to the thymoquinhydrone resulting from the union of
thymoquinone and hydrothymoquinone. A colorless oil to which
has been added the merest trace of hydrothymoquinone and thymo-
quinone acquires the same red-brown color.
. It has been noticed repeatedly that both the phenol and non-
phenol portion of these oils as well as of other oils containing thymol
or carvacrol, when rectified are colorless but very rapidly resume
the reddish-brown color of the original crude oil. The coloring
matter, thymoquinhydrone, of the crude oil is always partly or
wholly decomposed by the aqueous potassa or soda used in the
separation of the phenol constituents. The bulk of the hydrothymo-
quinone resulting goes into the aqueous alkaline solution and upon
regeneration with acid and subsequent distillation is found in the
colorless phenol oil. The readiness with which hydrothymoquinone
can be oxidized, as has been previously pointed out, soon results
in the formation of some thymoquinone which unites with more
hydrothymoquinone to form the colored quinhydrone and the phenol
oil again becomes colored. *
The bulk of the thymoquinone, on the other hand, is dissolved
in the hydrocarbons and other non-phenol constituents and upon
distillation is therefore found in the colorless non-phenol oil. As has
been previously stated, thymoquinone when dissolved in limonene,
cymene or pinene is changed by a process of auto oxidation to
hydrothy moduinone and some other compound. This same process
taking place in the colorless non-phenol oil which consists largely of
cymerie, would result in the formation of thymoduinhydrone and the
oil would again be colored. &
... That the pigment, thymoquinhydrone, does not exist in all parts
of the plant is shown by the fact that when the leaves of the fresh
herb of Monarda fistulosa are carefully removed from the purple-
colored stems and flowers and distilled alone a colorless oil is ob-
10 Pharm. Rev., 21, p. 200, 244,
10
tained. The presence of solid thymoquinhydrone or "its metallic
derivatives is a highly probable explanation of the purple color of
the stems of various Monarda species. The oil from the sun dried
leaves, however, is colored. This can be explained by the fact, as
has been shown by Rabak, 11 that the ferment obtained from the
fresh leaves of Monarda fistulosa, readily oxidizes the hydrothymo-
quinone to thymoquinone with the intermediate formation of thy-
moguinhydrome.
Upon the distillation of the carefully picked corollas of Monarda
fistulosa, a dark red oil was obtained from which a small quantity
of the purple thymoquinhydrone itself was isolated. It is theréfore
the thymoquinhydrone which produces the purple-pink color of these
flowers. That the quinhydrone pigment of the flowers is not found
in the leaves of this species is in harmony with the observed fact,
as will be shown repeatedly in the following pages, that a flower
often contains a compound which is an oxidation product of a con-
stituent found in the leaf. The comparatively wide distribution in
the vegetable kingdom of the two isomeric monatomic phenols,
thymol and carvacrol, both of which yield the same hydrothymo-
quinone will undoubtedly prove a ready explanation of the color of
other flowers, besides those already examined.
The presence of two phenol hydrogens in the commonly accepted
formula of the quinhydrones, admits of a variation in the tints of
the same fundamental color, due to their replacement by basic
elements or groups. Attention may be called to the fact that the
practically odorless varieties of Coleus, also a labiate species, com-
monly used as border plants in gardens because of their gaudy
colors, have been made to yield a trace of volatile oil resembling in
color the phenol solution of thymoquinhydrone.
According to Hessel” benzohydroquinone is found in a free con-
dition to an extent of from 2–5 percent in the oil from the flowers
as well as other parts of Protea mellifera, a South African plant.
Although no other members of this series of compounds have as
yet been found as a normal constituent of plants, several plant
substances very readily yield hydroquinones or derivatives thereof.
Thus the glucoside arbutin, by the action of a ferment, has been
11 Pharm. Rev., 22, p. 190.
12 Ann. d. Chem., 290, p. 319.
11
shown by Kawalier 18 to yield hydroquinone and by another investi-
gator 14 to yield both benzohydroquinone and hydrotoluguinone.
Not only is the fact that arbutin yields hydroquinones upon
hydrolysis important in that it gives rise to the possibility of the
occurrence of hydroquinones and consequently quinhydrones as pig-
ments in plants, but the occurrence of the glucoside arbutin in
the leaves of 6aultheria procumbens, Uva ursi and other plants of
the Ericaceae, affords an explanation of the reddish tint commonly
acquired by their leaves in the fall. As the life process of the leaf
comes to a standstill in the fall, the presence of hydrolizing ferments
can easily cause the formation of hydrobenzoquinone which in turn
may be oxidized to benzoquinone by an oxydase, the partial oxida-
tion resulting in the formation of the intermediate colored quin-
hydrone. If this oxidation continue all of the hydroquinone will be
oxidized to quinone, in which case the leaf may be colored yellow
after the disappearance of the reddish tints. The continuation of
the same process of oxidation may later givé rise to the formation
of brown pigments.
It is also of interest to mention that according to Emmerling
fresh grass when allowed to ferment yields benzoquinone upon
distillation with steam.
Quercite, found in large quantities in the acorn, upon heating
loses three molecules of water and forms hydrobenzoquinone as
shown by the following formula:
CHOH 98
N
Honº NCHOH HC / Nºon
| - | + 3H2O
noneycaon HOC % CH
§ NZ
HCH CH
The mono ethyl ether of hydroquinone has been found in small
quantities in the oil of star anise. 15
CnH2n-6.
There is only one quinone known which belongs to the formula
of saturation CnHng–6 viz. 5, 6, 7, 8, Ar-tetrahydronaphthoguinone
1, 4. This is a reduced naphthoguinone. Its corresponding hydro-
1s Ann. d. Chem., 84, p. 358.
14 Ann. d. Chem., 177, p. 338.
15 Ber. von S. & Co., Oct. 1895, p. 6.
- 12
º
quinone as well as the underlying hydrocarbon are known. The
Quinhydrone corresponding to these compounds has not been ob-
tained as yet. The hydroquinone is white while, its quinone is yellow.
CnH2n-s.
There are no quinone-like compounds known belonging to the
degree of Saturation CnH2n-s. Only one compound of known con-
sfitution important as a plant pigment can be referred to a hydro-
carbon belonging to this degree of saturation, viz. daphnetine. This
compound no longer contains two carbonyl groups like the quinones,
but one carbonyl group and an oxide oxygen, making it partly
heterocyclic. s :
Daphnetime can be regarded as a product of inner dehydration,
viz. a lactone, of trihydroxycinnamic acid -
() H
no/N ºntoon
* N/oil
in which one of the hydroxy groups is in ortho position to the un-
Saturated side chain. From this point of view, the tri-hydroxy-
cinnamic acid is therefore, a 6-hydroxy acid.
The wide occurrence of cinnamic acid and of hydroxy cinnamic
acids in nature shows the very close relation existing e. g. between
daphnetine, a dyestuff, and cumarine, umbelliferone, etc. odoriferous
plant principles, thus emphasizing the fact that in the laboratory
of different plants there can evidently be produced comparatively
different compounds from the same basal substance by means of
very simple chemical changes.
In the accompanying chart, the relation of a number of plant.
constituents, found in a great variety of plants, to the same basal
substance is shown. Starting with benzaldehyde, which is found so
widely distributed in nature, a great variety of plant subtances can
be obtained by means of the most simple chemical reactions, such
as readily take place during the life of a plant.
On the one hand, by oxidation, there can be formed either
benzoic acid or salicylic aldehyde, both of which by further oxidation
will yield salicylic acid. From this, by condensation with methyl
&
Q 7
X
z 2
N ſº /
|CŞ
|
/
Benzaldehyde.
ſ
§
X.
2O.
Ž y
‘O
º,
->
ſºcooh
|
Ny/
Benzoic acid.
/\, ( / H.
| Cºso X.
Joh
Salicylic aldehyde.
/ SU/H
| | *SO + CH3OH . |
*H.,,,
*Cool,
. Tº S.
N
|
is Z
Cinnamic acid.
X. Af
ſ YooH -
Joh. -*-º-º-º-º-º-º-º:
Salicylic acid. .
Z' N cº H
NO
-> | |
HO/Ny/
OCH3
Vanillin.
(H=CHCOOH
Hoº
O.H
Caffeic acid. .
| |
—
ſ CH=CH-COOH ºCH=CHCOOH
-- O -
|
Joh
Hydroxy cinnamic acid.
/ YCOOCHA (\cooch,
JoH → UNHe
Methyl salicylate. Anthranilic acid.
().H
(H=(XH HO/ NCH=CH
S / * >C=o +9. | Sc=o
$’/ N/NO/ o/
/ €.1 m arine. Daphnetime.
& /\
#|
| |
`-- * o OH ..
|
Joh
Trihydroxy cinnamic acid.

14
alcohol, methyl salicylate is formed. Of these products all three
have been isolated from the flowers of Spirea ulmaria. By the action
of ammonia on the methyl salicylate, the methyl ester of anthranilic
acid is produced, which is the odoriferous constituent of the orange
flowers. Instead of a mono-hydroxy-benzaldehyde (salicylic alde-
hyde) the benzaldehyde can also yield by oxidation, poly-hydroxy-
derivatives. The methyl ether of the 3, 4, di-hydroxybenzaldehyde
is waniblin.
On the other hand, by the condensation of benzaldehyde with
acetic acid, cinnamic acid is obtained, which by oxidation will yield
different hydroxy derivatives. If one of the OH groups is in ortho
position to the unsaturated side chain condensation may take place
forming an inner anhydride. Thus cumarine, the odoriferous con-
stituent of several plants, is the lactone of o-hydroxy cinnamic acid
and the plant dyestuff daphnetine is the lactone of 2, 5, 6, trihydroxy
cinnamic acid. With the exception of the dihydroxybenzaldehyde
underlying vanillin and the trihydroxy cinnamic acid underlying
daphnetine, all of these compounds have been repeatedly isolated
from different plants.
When it is remembered that the 6-hydroxy acids have a greater
tendency to form lactones than any other hydroxy acid, it is not
surprising that in the case of daphnetine, only the lactone and not
the trihydroxy cinnamic acid has been isolated from the plant. That
these hydroxy acids are formed in the plant and can, with proper
care to avoid dehydration, be isolated from the plant, is shown by
the fact that the monohydroxy cinnamic acid and its lactone,
cumarine, have been isolated from sweet clover, Melilotus officin-
alis 16 17, and from the leaves of Angrecum fragrams. 18 19
It is of interest to call attention to the following possible ex
planation of plant economy. Cumarine, which has the formula e-
CH OH e CH
() ºr ^^-
| ſº
/N N
N/ o–6–o \{ o-c-o


1 & Ann. d. Chem. Suppl. 8, p. 30.
16 Berz. Jahresb. 14, p. 31.1.
17 Ann. d. Chem. 76, p. 354.
15
is thé odoriferous constituent of the sweet clover and is, therefore, a
possible source of the yellow pigment daphnetine, which is a dihydroxy
cumarine, the metallic derivatives of which have been found in the
yellow flowers of the sweet clover.18
Daphnetine also occurs potentially as the glucoside daphnine in
Daphne alpina. It is slightly yellow in color, forms so-called salts
with metals, the potassium derivative having an intense yellow
color. With salts of aluminum and chromium as mordants it dyes
wool or cotton fibers yellow. When iron salts are used as mordant,
an olive-black color is produced.
Cn H2n-10.
The group of naphtoguinones belong to the degree of saturation
CnH2n-10. There are three naphtoquinones known which can be re-
ferred to the hydrocarbon naphthalene: 1, 4, naphtoquinone, 1, 2,
naphtoquinone and 1, 8, naphtoquinone in which each cycle contains
orie of the carbonyl groups. All three of the corresponding hydro-
naphtoquinones have been prepared and one naphtoquinhydrome,
viz. 1, 4, naphtoquinhydrone. This is a dark purple substance.
Bara quinones derivable from a-methylnaphthalene; 2, 6, di-
methylnaphthalene and 2 ethopropylnaphthalene are known. None
of the hydroquinones or quinhydrones corresponding to these com-
pounds have been prepared.
Besides the group of naphtoguinones, guajenequinone belongs to
the degree of saturation, CnH2n-10. It is prepared by oxidizing the
hydrocarbon guaiene obtained from guajac resin. Neither the con-
stitution of the hydrocarbon nor that of the guajenequinone are
known.
The hydronaphthoguinones corresponding to the quinones under
this formula of saturation are still more readily oxidized to quinones
than the hydroquinones of the benzene series. On the other hand
the naphthoguinones are very stable compounds. They can not be
reduced to the corresponding hydroquinones with sulphur dioxide as
were the quinones under the degree of saturation CnH2n-4, but re-
quire some stronger reducing agent. It is undoubtedly for this reason
that so few of the hydronaphthoguinones corresponding to known
naphthoguinones have been prepared. The 1, 4 naphthoguinhydrone
results very readily upon mixing solutions of socalled a-naphtho-
18 Berz. Jahresb. 14, p. 311.
16
quinone and the corresponding hydronaphthoguinone, The 1, 8 di-
hydroxynaphthalene when shaken in , aleoholic, solution, with air,
gradually turns violet. This color may be due to the presence of a
quinhydrone, a part of the dihydroxynaphthalene being oxidized to
the naphthoguinone, which unites with some of the dihydroxynapha-
lene to form a naphthoguinhydrome. Although both v. the 1, 8 di-
hydroxynaphthalene and the 1, 8 naplithoguinone are known , the
quinhydrone has not yet been identified. . . . . . . . . . . * *
• These naphthoguinones form a number of hydroxy derivatives
of which some of the corresponding hydroxy-hydronaphthoguinones
are also known. None of the hydroxynaphthoguinhydrones are
known. {
The hydroxyhydronaphthoguinones are colorless crystalline sub-
stances which in alkaline solution are readily, oxidized to the hydroxy-
naphthoguinones. 1, 4, 5, Trihydroxynaphthalene, also called hydro-
juglone; is found in all the green parts of the walnut tree, Juglans
regia 19, and especially in the green shells of the nuts. The yellowish-
red shells of the ripe walnuts, no longer contain the hydrojuglon. In
the ripening of the nuts, the colorless, hydrojuglon is undoubtedly
oxidized by ferments or otherwise to the yellowish-red hydroxy-5-
naphthoguinone 1, 4, called juglone, to which the color of the ripe
walnut shells is due. In fact, the color need not necessarily be
attributed only to the hydroxynaphthoguinone for it is known that
this latter eompound is readily oxidized by the air to a dihydroxy
derivative which has a still darker color. “
The color of the hydroxynaphthoguinones varies from yellow to
dark red-black with the increase in the number of hydroxy groups.
The change in color is not quite so marked as in case of the hydroxy-
quinones of the formula of saturation CnH2n-4 because in the latter
case a longer and more gradual series of compounds is known.
The hydroxynaphthoguinones form derivatives with the metals which
have a blue or violet color with the exception of the metallic deri-
vatives or 8-2-hydroxynaphthoguinone which are red. The com-
pounds with the alkali metals and ammonia are usually soluble
while the compounds formed with the heavy metals are insoluble.
In the hydroxynaphthoguinones; we have the first occurrence of
compounds of a quinone nature, which possess the property of dye-
ing mordant fibres. Their dyeing properties, however, are very weak,
19 Ber. 17, p. 24.12. * * * * * * * * * * * *
17
only one of the compounds having sufficient dyeing capacity to make
it of commercial importance. This is the 5, 6, dihydroxynaphthol
quinone 1, 4, commonly called naphthazarine.
CnH 2Il-12.
Under the degree of saturation CnH2n-12, are found the quinones
and their reduction products referable to diphenyl and its alkyl
derivatives. If one of the phenyl groups is changed to a quinone,
there is possible a series of compounds which can be regarded as
phenyl derivatives of the quinones having the degree of Saturation
CnH2n-4, for example phenyl-benzoquinone,
If however both phenyl groups are changed to quinones there is Ob-
tained a series of diquinones. Representatives of both these classes
have been prepared.
The hydroquinones corresponding to all the known quinones-
derivable from diphenyl have been prepared and likewise all the
quinhydrones.
The hydroquinones of this formula of saturation are colorless
crystalline substances having properties very similar to the hydro-
quinones under CnH2n-4. Dihydro-ditoluquinone is recorded as being
light yellow in color. The purity of this compound may be questioned,
inasmuch as the other hydroquinones of this as well as other series
are colorless.
The quinhydrones under this formula of saturation are highly
colored crystalline substances which are much more stable than the
quinhydrones heretofore met with. They are not so readily broken
up by the Ordinary organic solvents into their components, quinone
and hydroquinone, but can be crystallized from these solvents.
The 2-cyclohexylnaphthoguinone referable to cyclohexylnaphtha-
lene and the acenaphthaquinone obtained by the direct oxidation of
the tricyclic hydrocarbon acenaphthene have not been thoroughly
studied.
Of only one of the quinones of the formula of saturation CnH2n-12,
18
is a hydroxy derivative known. The tetrahydroxy-phenylbenzo-
Quinone and its reduction product the hexahydroxybiphenyl are both
known. The former is blue while the latter is colorless. The cor-
responding quinhydrone is unknown. The di-, tri- and tetramethyl
and tetra-ethyl ethers of the tetrahydroxyphenylbenzoquinone have
been prepared. Here again the change of color from blue of the
hydroxyquinone to the yellow of the quinone, brought about by the
replacement of the hydrogen of the hydroxy group by alkyl radicles
can be seen. The tetrahydroxy-phenylbenzoquinone is blue while the
ethers are yellow or orange. The tetramethyl ether, also called
cedriret and coerulignon, is described as being blue while the tetra-
ethyl ether as well as the other ethers are yellow. The fact that
this blue compound is obtained by the oxidation of the tetramethyl
ether of the tetrahydroxyphenylbenzohydroquinone, seems to indicate
that it was not a quinone, but the tetramethyl ether of a quinhydrone
which was obtained and which one would expect to be blue.80
Under the degree of saturation CnH2n-12, there is furthermore a
hydroxy derivative of amylenenaphthoguinone, the amylenenaphtho-
quinone itself not being known. This is a yellow compound called
lapachol, found in “Gruenherz” of Surinam 21, in Lapacho wood 22 and
in Bethabara wood.23 The metallic derivatives of this compound
are red. Upon reduction with sodium it yields the very unstable
hydrolapachon. -
CnH2n-14.
Very little is known about the quinones of the degree of satura-
tion CnH2n-14. The three methylenediphenyl hydrocarbons yield,
upon oxidation with chromic acid, different quinones.
Practically all the substances of known constitution which are
important as plant pigments and which are not of a quinone nature,
are referrable to a few hydrocarbons under two different degrees of
saturation, viz. CnH2n-14 and CnH2n-16. There is one exception
viz. daphnetine, which has already been discussed under the formula
of saturation CnH2n-s.
By referring these so-called dyestuffs under the formula of satura-
tion CnH2n-14. to hydrocarbons from which they can be theoretically
20 Ann. d. Chem., 169, p. 229.
21 Ztschr. f. Chem., 1867, p. 92.
22 Jahresb. u. d. Fortschr. d. Chem., 1858, p. 264.
23 Am, Chem. Journ, 11, p. 267.
19
derived and from which in at least a few cases, they have been
synthesized we find a strikingly simple relationship manifesting it-
self. All the compounds of this degree of saturation can be referred to
Diphenylmethane
1, 1, diphenylethane
1, 2, diphenylethane
1, 2, diphenylpropane
These hydrocarbons have all been prepared and can be very readily
synthesized forming well characterized compounds. 24
Although as yet none of these hydrocarbons have been isolated
from plants, it is again very evident that the different plants work
with comparatively simple and very similar basal substances, result-
ing in the formation of a large number of different compounds.
Knowing the great readiness with which these fundamental
hydrocarbons can be oxidized even in the laboratory to their corre-
sponding Oxygen derivatives, their presence as such in a matured
plant could hardly be looked for. A few examples will suffice. The
hydrocarbon diphenylmethane, can be very readily oxidized to its
corresponding diphenyl ketone.95
O
|
C
º
#2 * 6 º 2
s.s 5 4 3
As the oxidation continues during the life process of the plant, there
would naturally result hydroxy derivatives of the diphenyl ketone.
If, however, the introduction of hydroxy groups takes place in
positions 5, 5’ (see formula above), the oxidation is followed by
inner condensation with the elimination of water. The resulting
compound, therefore, is no longer a diphenyl ketone derivative, but
a tricylic compound like euxanthone.
O
|
C
(YYY
|
º Y V
24 Beilstein — Handbuch der organischen Chem., vol. II, pp. 164, 230, 232, 23
25 Ann. d. Chem., 159, p. 377. *
20
This statement is borne out by the fact that although a large num-
ber of such inner anhydrides are known corresponding to hydroxy
derivatives of diphenyl ketone containing the hydroxy groups in
positions 5,5’, the hydroxy derivatives themselves have been ob-
tained in only a few cases, and in those cases where the compounds
were obtained they were so unstable that they changed to the
anhydride while attempting to take the melting point. 26
It is well known that 1, 1, diphenylethane upon oxidation also
yields diphenyl ketone. 27 The oxidation of 1, 1, diphenyl ethane,
on the one hand, in the plant would result, therefore, in the forma-
tion of analogous substances as were obtained from diphenylmethane.
If, on the other hand, a less violent oxidation were to take place
than usually results from the üse Of our ordinary laboratory re-
agents, we would expect, not the complete oxidizing off of the
methyl side chain, but the oxidation of the methyl radical to a car-
boxyl radical, resulting in the formation of an acid. It is rather
remarkable that such a compound, phoeniceine, has actually been
isolated from Copaifera bracteata.
O
!
^^^
A Y
th __ V ºv
/ Nº Diphenylketone.
| | | COOH
/ NZ * O t H
1, 1, diphenylethane. A º
| |
J J
Phoeniceine.
With reference to the constitution of the dyestuffs themselves,
most of them can be placed into one of the two groups: 1) Those
which are hydroxy or methoxy derivatives of diphenyl ketone,
C
| | | |
s/ N/
- 26 Ann. d. , Chem, , 254, pp. 300, 302.
27 Beilstein — Handbuch der organischen Chem., II, p. 231.
21
and 2) those which are hydroxy or methoxy derivatives of xanthone
O
* s |
C
ſº
| | | |
Nºgº
s In addition, attention may be called to the fact that the xan-
thones (from the Greek, xanthos meaning yellow) contain in addition
to the OH and substituted OH groups, viz. OCH3, a carbonyl group
and a cyclic oxide oxygen thus rendering the compound heterocyclic.
There are three dyestuffs which can be regarded as derivatives
of diphenyl ketone, viz. cotoine, a dihydroxy 1, 5, methoxy 3 deri-
vative found in the Coto bark; maclurin, a pentahydroxy 3, 4, 1’,
3’, 5’, derivative found in Morus tinctoria, L., and kinoine, a tetra-
hydroxy 2, 2’, 3', 4', methoxy (?) derivative occurring in kino. They
are colorless or very slightly yellowish crystalline compounds occur-
ring in the plant as such. They form yellow solutions with caustic
alkalies, which turn brown in contact with the air and give yellow
precipitates with lead acetate. Upon heating with strong alkali or
acid, cotoin breaks up into phloroglucin and protocatechuic acid;
and upon heating with hydrochloric acid, kinoine breaks up into
methyl chloride, gallic acid and pyrocatechin. Upon the reduction
of maclurin with nascent hydrogen, there results phloroglucin, and
a colorless compound C14H10O3 called machromin. 28. Its aqueous
solution gradually turns an intense blue. This reaction is hastened
in the presence of ferric chloride. The blue oxidation product can
be reduced to the colorless machromin.
The dyeing properties of this sub-group have not been well deter-
mined.
In the xanthone group, there are four compounds of kuown con-
stitution obtained from plant sources, viz.:
Euxanthone, a 2, 7, dihydroxy derivative occurring as euxanthinic
acid in a dyeing substance obtained from India;
Gentiseine, a 1, 3, 7, trihydroxy derivative and
Gentisine, a 1, 3, dihydroxy-7-methoxy derivative obtained from
the root of Gentiana lutea ;
28 Jahresb. u. d. Fortschr. d. Chem., 1864, p., 558.
22
Datiscetine, a 1, 2, methoxy-3, 4, dihydroxy derivative occurring
as the glucoside datiscine in Datisca cannabina.
Euxanthone is a light yellow crystalline substance forming color-
less compounds with potassium, sodium and magnesium, a red com-
pound with barium. Its corresponding ethers and esters are yellow.
Heated with potassium hydroxide, it yields resorcin and hydro-
quinone. By reduction a violet black substance C26H13OT is obtained.
Gentisin is the methyl ether of gentiseine. The latter has not been
found in the plant as such, but is obtained by treating the gentisin
with hydriodic acid. Both gentisein and gentisin are light yellow
crystalline substances giving yellow solutions with the alkalies. When
heated with potassium hydrate there results in both cases, phloro-
glucin and oxysalicylic acid. t
Datiscetin is also a light yellow crystalline substance which forms
yellow metallie derivatives.
The intensity of the dyeing property of the xanthone group of
dyestuffs apparently increases with the increase in the number of
hydroxy groups in the molecule. Euxanthone, which contains but
two hydroxy groups, has very weak dyeing properties. Mono hydroxy
derivatives of xanthone which have been prepared synthetically
appear to have no dyeing properties whatever. Gentiseine on the
other hand, a trihydroxy derivative, dyes wool or cotton with a
bright yellow color. Again gentisin which is a methyl ether of gen-
tiseine and, therefore, has but two hydroxy groups, has about the
same weak dyeing properties as euxanthone. Perkin explains the
fact that gentiseine is a much stronger dyestuff than gentisin, by
assuming that the dyeing property lies in the one particular hydroxy
group which in gentisin becomes a methoxy group and, therefore,
the dyeing property is destroyed.
Inasmuch as the previously mentioned compounds with two
hydroxy groups still have some dyeing properties, although much
weaker than the compounds with three hydroxy groups, it seems
much more logical to attribute the difference in dyeing intensity to
the increase or decrease of the number of hydroxy groups rather
than to a change in the nature of any one such group. This idea
is further exemplified in the case of the dyeing properties of the
hydroxy anthraquinones.
The strength of the dyeing properties of these compounds as
dependent on the number of OH groups is entirely comparable to
23
the color of the hydroxyquinones which changes from yellow to blue
with the increase in the number of () H groups and from blue to
yellow by changing the OH groups to OCH3, OC2H5 etc. This has
already been pointed out. *
Phloretine can be regarded as a tetrahydroxy derivative of
phenyl-phenylethyl ketone.
º
/Nº CHCH3
N
It occurs potentially as a glucoside in the root bark of apple, cherry
and plum trees, also in the leaves of Smilax glycyphylla.
Although genisteine, phoeniceine and curcumine are derivable
from homologous hydrocarbons their constitution is very different
from each other as well as from the other dyestuffs under this degree
of saturation. This again emphasizes the difficulty of trying to find
any relation between these compounds without referring them to
their underlying hydrocarbons. Although these compounds are
hydroxy and methoxy derivatives of the respective underlying hydro-
carbons, they differ from the other compounds in that they do not
contain a carbonyl group.
Genisteine and phoeniceine contain an oxide oxygen and in addi-
tion phoeniceine contains a carboxyl group. Curcumine contains a
carboxyl group but no oxide oxygen.
CnH2n-16.
The degree of saturation CnH2n-16 contains the anthraquinones
and their derivatives. A great number of these quinones have been
carefully studied inasmuch as they are very readily prepared and
their derivatives are important as dyestuffs. The majority of these
compounds can be prepared by the direct oxydation of the anthra-
cene hydrocarbons to which they have been referred.
Two anthraquinones, ortho and para, derivable from anthracene,
have been prepared. Quinones derivable from two different methyl-
anthracenes, nine different dimethyl-anthracenes and three different
trimethyl-anthracenes are known. Only one corresponding hydro-
Quinone is known, viz. Oxyanthranol, the hydroquinone correspond-
24
ing to anthraquinone. Not a single quinhydrone has as yet been
prepared.
The members of this group of quinones are yellow crystalline
substances which are exceedingly stable. Strong oxidizing agents
have little or no effect and when treated with strong reducing agents,
they are readily reduced to the underlying hydrocarbons. It is un-
doubtedly on account of this behavior that none of the hydroanthra-
quinones are known.
The degree of saturation CnH2n-16 also contains the following
quinones:
Methanthraquinone,
Phenanthrenequinone,
Retenequinone,
Dithymolethylenequinone.
The constitution of methanthraquinone has not been determined.
It is obtained upon the oxidation of the hydrocarbon methanthrane,
C15H12. Upon reduction with sulphur dioxide, a white substance is
obtained which is possibly the correponding hydroquinone.
Phenanthrenequinone is obtained by the oxidation of the hydro-
carbon phenanthrene C14H10. Upon reduction with sulphur dioxide,
it yields phenanthrenehydroquinone which absorbs oxygen from the
air forming a black quinhydrone. Upon further oxidation the
phenanthrenequinone is again formed.
Retenequinone is the methyl-isopropyl derivative of phenanthrene-
quinone. It is obtained by the direct oxidation of the hydrocarbon
retene C18H18. A colorless reduction product and a brown quin-
hydrone have been obtained but not well characterized.
The hydroxy derivatives of the anthraquinones and their ethers
form a very important group of compounds. Not only have a very
large number of them been prepared synthetically because of their
importance as dyestuffs, but a considerable number have been
isolated from plant sources. Corresponding hydroxy hydroquinones
and their ethers and the hydroxyquinhydrones and their ethers are
unknown.
It is of interest to note that several of these compounds are
found in the same plant.
From the root of Oldenlandia umbellata.”8 there has been isolated
2, hydroxyanthraquinone; alizarine, 1, 2, dihydroxyanthraquinone
28 Journ. Chem. Soc. 63, p. 1177; 67, p. 822.
25
as the glucoside ruberythrinic acid; the monomethyl ether of alizarine,
2, 3, dihydroxyanthraquinone monomethyl ether; and 1, 2, 3, tri-
hydroxyanthraquinone dimethyl ether.
Madder root contains alizarine, 1, 2, dihydroxyanthraquinone; 29
purpurine, 1, 2, 4, trihydroxyanthraquinone 30 and rubiadine, 2, 4,
dihydroxy-methyl-1-anthraquinone 81 as glucosides.
5, 7, dihydroxy-methyl-2-anthraquinone and a tetrahydroxy
derivative of a dimethylanthraquinone have been isolated from the
root bark of Morinda umbellata.82 Morinda citrifolia, however, con-
tains morindon, a trihydroxy derivative of 2-methyl anthraquinone
as the glucoside morindine.88
A dihydroxy derivative of a methylanthraquinone called chryso-
phanic acid has been isolated from several species of Rumex 34, from
Senna, leaves 85 and from Cascara Sagrada.86
Barbadoes aloes 87 contains 1, 4, 7, trihydroxy-2-methyl anthra-
quinone. Emodine, a trihydroxy derivative of 2-methyl anthraquinone
is found as the glucoside franguline in Rhamnus frangula 88; as the
glucoside polygonine in Polygonium cuspidatum 39 and as the gluco-
side purschianine in Cascara Sagrada.40 Emodine methyl ether and
several other anthraquinone derivatives have been isolated from the
root bark of Ventilago madraspatana. Their constitution, however,
has not been definitely determined.
Although these compounds have for the most part been isolated
from the roots or barks of the plants from which they can be ob-
tained in considerable quantities, their presence in smaller quantities
in other parts of the plant is not improbable. Inasmuch as the
hydroxy derivatives are in themselves red or yellow and their metallic
derivatives blue, their presence in even very small quantities in the
flowers of these same plants would afford a simple explanation of
the color of the flower. —es
The hydroxy derivatives of the anthraquinones and alkyl anthra-
quinones are crystalline substances, all of which can readily be sub-
29 Journ. Chem. Soc. 63, p. 1177.
; º; Bºsić, p. 117.
: ſº gº sº; # #38.
84 Ann. d. (Xhem. 107, p. 324.
85 Jahresb. u. d. Fortschr, d. Chem., 1864, p. 555.
36 Compt. rend. 129, p. 60.
87 Bull. Soc. Chim. (3) 23, p. 785.
38 Berichte 9, p. 1775.
S9 Journ. Chem. Soc. 67, p. 1085.
- 40 Journ. Am. Chem. Soc. 20, p. 544.
26
limed. They yield metallic derivatives, the color of which varies
from a yellowish-red to blue. The color of these metallic derivatives
seems to be dependent upon the relative positions of the hydroxy
groups. Thus the monohydroxy derivatives form red salts. The
polyhydroxy derivatives which contain hydroxy groups connected
to at least two neighboring carbon atoms, yield blue or violet
metallic derivatives. For example:
1, 2, dihydroxyanthraquinone forms blue metallic derivatives
2, 3, dihydroxyanthraquinone { { ( & ( & ( &
3, 4, dihydroxyanthraquinone ( & * { { % & C
1, 2, 3, trihydroxyanthraquinone ( & { { ( & { {
1, 2, 5, trihydroxyanthraquinone { { { { { % & C
1, 2, 7, trihydroxyanthraquinone & & { { ( & & 4
1, 2, 3, 5, 6, 7, hexahyroxyquinone “ ( & { { ( &
In the case of those polyhydroxy derivatives, however, which do
not contain hydroxy groups connected with neighboring carbon
atoms, the metallic derivatives are yellow or red. For example:
1, 3, dihydroxyanthraquinone forms red metallic derivatives,
3 - 5 y
1, 5 ( & 4 & ‘‘ red & C & C
y 3.
1, 8, t & { { “ yellow { { & 4
2 6 4 & { { * { red { { { {
y y
1, 4, 7, trihydroxyanthraquinone “ yellow-red “ { {
2, 4, 6, 8, tetrahydroxyanthraquinone “ yellow-red “ K &
The variation in the color of the different hydroxy derivatives, is
dependent not only upon the number of OH groups in the compound
but on their relative position. If we compare such compounds as:
1, hydroxy anthraquinone................................. Orange,
1, 2, dihydroxyanthraquinone........................... red,
1, 2, 3, trihydroxyanthraquinone..................... brown,
1, 2, 3, 4, tetrahydroxyanthraquinone............. green,
1, 2, 3, 4, 5, 6, hexahydroxyanthraquinone...dark-green,
in which the number of OH groups is increased by successive addi-
tions to neighboring carbon atoms, it is evident that the increase
of color from yellow to green, is brought about by the increase in
the number of OH groups. By distributing the hydroxy groups
over the entire compound, the color of the resulting polyhydroxy
derivative is changed toward yellow. For example by connecting
the two hydroxy groups in the dihydroxyanthraquinones with car-
27
bon atoms which are not neighboring, the color of the resulting
compound goes back to that of the yellow monohydroxy derivatives.
Thus while 1, 2, dihydroxy anthraquinone (see list above) is red,
1, 3, dihydroxyanthraquinone, 1, 4, dihydroxyanthraquinone and
1, 5, dihydroxyanthraquinone are yellow.
Again while the 1, 2, 3, 4, tetrahydroxyanthraquinone is green,
the 1, 3, 5, 7, tetrahydroxyanthraquinone is yellow.
As was the case under the previous degrees of saturation, the
changing of hydroxy to methoxy or ethoxy groups, changes the
color of the resulting compound more towards the color of the
original quinone. Therefore the ethers of the hydroxyanthraquinones
are yellow or yellowish-red.
The importance of the natural dyestuffs alizarine and purpurine,
together with the exact knowledge of their constitution soon led to
the synthesis of a large number of other hydroxyanthraquinones
with the hope of finding new dyestuffs. It was soon discovered,
however, that many of the compounds obtained did not have the
property of dyeing fibres mordant with aluminum or iron salts,
while the majority of those which have dyeing properties dye so very
similar that it is almost impossible to tell them apart. Further-
more, it was also known that by the introduction of another OH
group, most of the non-dyeing hydroxyanthraquinones, acquired
dyeing properties. The dyeing property of these substances is, there-
fore, dependent not only on the number but also on the relative
position of the OH groups.
In 1887, Liebermann and Kostanecki41 undertook a study of a
large number of hydroxyanthraquinones in order to find out what
the positions of the OH groups are on which the dyeing property is
dependent. That it requires at least two hydroxy groups in order
that the anthraquinones may become dyestuffs is shown by the fact
that all monohydroxyanthraquinones have no dyeing property what-
ever. Of the nine known dihydroxyanthraquinones, only alizarine,
having the hydroxy groups in positions 1 and 2, has strong dyeing
properties. Hystazarine, 2, 3, dihydroxyanthraquinone, not known
at Liebermann’s time, also has dyeing properties, but they are some-
what weaker than those of alizarin. That the dyeing property of
alizarine is not dependent on only one of the two hydroxy groups
is shown by the fact that the monomethyl or ethyl ether of alizarin
41 Ann. d. Chem. 240, p. 245.
28
does not dye mordant fibers. From this Liebermann draws the con
clusion that the polyhydroxyanthraquinone must have two of its
hydroxy groups in positions 1 and 2 in order that the compound
may have dyeing properties.
By applying this rule to other polyhydroxyanthraquinones be-
sides the dihydroxy derivatives, the following facts can be observed :
All the known tribydroxy anthraquinones have the property of
dyeing mordant fibers and all have two of the three OH groups in
positions 1 and 2, or similar positions. They can therefore be re-
garded as hydroxy alizarines. This also applies to the methylanthra-
quinone derivatives.
All the tetrahydroxy anthraquinones which have strong dyeing
properties have two of the four OH groups connected to carbon
atoms 1 and 2. The tetrahydroxy derivative in which the OH groups
are in positions, 1, 4, 5, 8,
O
|
C X
º
| |
º Y
O
has no dyeing properties whatever. On the other hand the 1, 3, 5, 7,
tetrahydroxyanthraquinone
X
O
|
X C
^^^
X
|
O
has some dyeing properties although very weak. It is theoretically
impossible to have penta and hexahydroxy derivatives in which two
of the OH groups are not connected to carbon atoms in position
1 and 2. Therefore all the known penta, and hexahydroxyanthra-
Quinones are good dyestuffs.
Although Liebermann has shown that all the hydroxyanthra-
quinones with possibly two exceptions which have dyeing properties
have hydroxy groups in positions 1 and 2, he has apparently made
29
no attempt to explain why compounds having OH groups in these
positions should have such properties.
Now, it is well known that the mordants which are used in dye-
ing with these substances are salts of aluminum, iron and chromium,
in other words salts of trivalent metals. The process of dyeing with
mordants depends upon the formation of the aluminum, iron or
chromium derivative and its deposition in the fiber. This being true,
one would possibly not expect the monohydroxyanthraquinones to
have dyeing properties, inasmuch as the union of three molecules
of the monohydroxyanthraquinone with one atom of aluminum,
Al= might hardly be expected to take place very readily.
On the other hand, by the introduction of more OH groups into
the same molecule the tendency to form these trivalent metallic
derivatives would be increased and it would be expected to be the
greatest in those cases in which the OH groups are connected to
neighboring carbon atoms. The bonds of the aluminum atom would
be subject to a less strain as it were, when they united with bonds
from neighboring carbon atoms, than when they united with bonds
from different molecules or from widely separated bonds in the same
molecule. From this standpoint, the 2, 3, dihydroxyanthraquinone
O
|
C
(YYYoh
| | | |
sºon
|
O
as well as the 1, 2, dihydroxyanthraquinone
should have dyeing properties. Both of these compounds are dye-
stuffs, the former not agreeing with the rule as laid down by Lieber-
II18,Illſl.
30
In those compounds in which the OH groups are not connected
to neighboring carbon atoms as is the case in the dihydroxyanthra-
quinones, 1, 3; 1, 4; 1, 5, etc., the separation of the OH groups
from one another decreases the tendency to form metallic derivatives
with trivalent metals and therefore these compounds have no dyeing
properties.
On the basis of the same reasoning, the least strain of all would
result and, therefore, an aluminum, iron or chromium derivative
would be most readil y formed in those cases in which there are three
OH groups connected to neighboring carbon atoms. This is sub-
stantiated by the fact that anthragallol, 1, 2, 3, trihydroxyanthra-
quinone
H
^^^on
|
JJJoh
O
O
|
C O
|
U
|
has more intense dyeing properties than alizarine, 1, 2, dihydroxy
derivative.
O
C OH
(YYYoh
| |
Nº.
6
Besides the group of hydroxyanthraquinones, the degree of
Saturation CnH2n-16 also contains hydroxy derivatives of phenan-
threnequinone. As in the case of the hydroxy derivatives of the
quinones in general, these substances are much more highly colored
than the phenanthrenequinone and the ethers are much less colored
than the hydroxy compounds.
The compounds belonging to the degree of saturation CnH2n-16
which are important as plant pigments but which do not belong to
the quinone group, can be referred to
31
Methyl-ethyl 5, 5’, diphenyl 1, 2, ethylene,
Diphenyl 1, 3, propene 1, &
Diphenyl 2, 3, propene 1,
Diphenyl 1, 4, butene 2,
Diphenyl 3, 4, butene 1.
There are furthermore two compounds whose constitution has
not been definitely determined which have been referred to a dicyclo-
hexadecaheptene and one whose constitution is also still in doubt
which has been referred to a tricyclo-tridecahexene.
Of these hydrocarbons, only one, viz. 1, 3, diphenylpropene 1
has thus far been prepared.
With reference to the constitution of the compounds themselves
most of them can be regarded as hydroxy and methoxy derivatives
of flavone g
O
|
C
2^/N
/--
i *º- N
Nº. N /
The flavones (from the Latin flavus, a, um, yellow) like the xanth-
ones in the previous degree of saturation contain in addition to the
OH and substituted OH groups, viz. OCH3, a carbonyl group and
a cyclic oxide oxygen thus making the compound heterocyclic.
The assumption generally made that the dyeing properties or
the color of a compound are due to the presence of certain chromo-
phorus groups, serves very well to show the relation between the
compounds of the xanthone and flavone groups, but fails utterly to
show any relation with those compounds which do not fall into
these two groups. No attempt has been made on the basis of chro-
mophorous groups to explain the fact that out of the great number
of known alkaloids, berberine alone should be possessed of color and
with dyeing properties. An apparent relation can readily be seen
by referring the berberine to its underlying hydrocarbon. This is
very similar to those to which the chromophorous dyestuffs have
been referred.
32
O
|
C 4.
ſ ºf ſ Yi
_/ N
N/ N2. sº < /
Diphenyl-l-3-propene-2. Flav One.
º |-º-º-º: N
| J |
N/N /N
CII3 cº
Methyl-2-ethyl-2'-diphenyl-1-2, ethylene.
CH2 O

| th-9

O
N /N () |
* Nº N \/~
()0H8 CH |
| |
cºº OCH3 ºº

Shoº.
| 1 , ), "Y Y|
/N /N CH2 | & |
Ny iſs Yá 2 vºl. ".
OH CH (H2
Berberine hydroxide. [3erberine.
The rather large number of dyestuffs belonging to the flavone
group, although occuring in a great variety of plants, bear a very
simple relation to each other. The first member, chrysin, is a
dihydroxyflavone; galangine and apigenine are both trihydroxy
derivatives of flavone, viz. 2, 1, 3, and 1, 3 4* respectively. **
Acacetine is a methylether of apigenine, the methoxy group
being in position 4/. Fisetine, luteoline and kaempherol are tetra-
hydroxy derivatives of flavone. Kaempherid is a methyl ether of
kaempherol. There are two pentahydroxyflavones, viz. Quercetin and
morin. Rhamnetin and isorhamnetin are methyl ethers of quer-
cetin and rhamnazin is a dimethyl ether of quercetin. Myricetin is
one of the theoretically possible hexahydroxyflavones.
These substances are all yellow crystalline compounds, and are
important not only as plant pigments but also as dyestuffs. Their
sodium, potassium and lead derivatives are yellow and with salts
33
of iron they give red or green solutions. They have been isolated
from a great variety of plants in which they all occur potentially
as glucosides with the exception of chrysine, galangine, luteoline
and kaempherid. These four are found in the plant as such. Quer-
cetin is found both in a free condition and as glucoside in a greater
number of plants than any other dyestuff of the flavone group. It
is obtained upon the hydrolysis of the glucosides quercitrin, robinin,
rutin, myrticolorin and osyritrin.
It is interesting to note that whereas acacetin, an apigenine-
monomethyl ether, is found as a glucoside in the leaves of Robinia
pseudacacia, a quercetin (a dihydroxyapigenin) glucoside is found in
the flowers. We have, therefore, again the occurrence in the flower
of a leaf constituent in a more oxidized condition.
The leaf buds of different species of poplar contain chrysin, while
the full grown leaves do not. Many of the compounds of the flavone
group occur in the flowers of different plants. Quercetin as a
glucoside, which is almost white, is found in the white blossoms of
Crataegus oxyacantha 42 while in the yellow flowers of Cheiranthus
cheiriº the yellow quercetin as well as its colorless glucoside are
found. The reddish-yellow flowers of Aesculus hippocastanum 44
contain both the glucoside quercitrin and the yellow dyestuff quercetin
in considerable quantity. The leaves and twigs, however, of this
same plant contain only mere traces of either quercitrin or quer-
cetin. The yellow flowers of Delphinium zalil45 contain quercetin
and isorhamnetin both free and as glucoside.
Robinin, the colorless glucoside of the yellow substance kaem-
pherol is found in the white flowers of Robinia pseudacacia 46. The
free kaempherol does not seem to occur in these flowers. These and
other cases which might be mentioned would indicate the possibility
of quercetin either as such or as its potassium or sodium derivative,
which are more intensely yellow, and of other flavone derivatives
producing the yellow color in some flowers. In fact the wide occur-
rence and behavior of quercetin has been made the basis of an un-
tenable hypothesis of plant pigmentation. (By Hlasiwetz.) That
these dyestuffs, or their yellow metallic derivatives, are not always
the pigments to which the flower owes its color primarily is shown
42 Journ. Chem. Soc., 69, p. 1570.
: ſº ſº. £, #19.
45 Journ. Chem. Soc., 73, p. 267.
46 Journ. Chern. Soc. 81, , p. 473.
34
by the occurrence in considerable quantity of the glucoside robinin
and its product of hydrolysis, the yellow kaempherol in the blue
flowers of Delphinium consolida. 47
In general the compounds of this group are much stronger dye-
stuffs than those of the xanthone group. This is to be expected
from the fact that most of the compounds contain a greater number
of hydroxy groups thus rendering more easy the formation of the
metallic derivatives of the trivalent metals used as mordants. Not
one of these compounds contains two hydroxy groups in positions
1 and 2, a condition which Liebermann and Kostanecki gave as
essential in the case of the anthraquinone dyestuffs.
Comparing the strength of the dyeing properties of these com-
pounds again from the point of view of the comparative tendency
to form metallic derivatives with aluminium, iron or chromium, it
is seen that those compounds are the strongest dyestuffs which have
two or more OH groups connected to neighbouring carbon atoms
Thus quercetin
()
|
OH C
/*N/NOH
| | | {T>0H
HON —N
N/Y 6ſ.
and rhamnetin
O
|
/
CH3ONº, C."
H
C
O
OH

2%
N
which is a methyl ether of quercetin, both have two hydroxy groups
connected with neighboring carbon atoms and both have approxi-
mately the same dyeing property. Isorhamnetin
º
OH C
º
| /Ts
º, ( >OH

47 Journ. Chem. Soc., 81, p. 585.
35
however, which is also a methyl ether of quercetin, on account of
the position of the OCH2 group, no longer has two hydroxy groups
connected with neighbouring carbon atoms and accordingly dyes with
less intensity. That the dyeing property in general can be decreased
by converting a hydroxy OH group to a methoxy OCH3 group is
again shown by the fact that whereas apigenine, a trihydroxy deri-
vative, dyes a bright yellow, acacetine, a monomethyl ether of api-
genine, dyes a very faint yellow about equal in intensity to the
dihydroxy derivative chrysine. Again kaempherid, a monomethyl
ether of kaempherol, dyes a lighter color than kaempherol.
Besides the flavone group of compounds, there still remain under
the degree of saturation CnH2n-16 several substances having a
different constitution, yet referable to hydrocarbons which are
homologues of the hydrocarbon underlying flavone.
Gossypetin, a yellow crystalline substance, is found in the yellow
flowers of Gossypium herbaceum in the form of a glucoside. Whether
the color of the flowers is due to the presence of some free gossype-
tin has not been determined. Its potassium derivative is yellow,
its lead compound red, and it gives green solutions with iron salts.
It is remarkable that indigo, a substance of an entirely different
nature, can be referred to the same hydrocarbon as gossypetin.
Indigo is found as the glucoside indican in Indigofera tinctoria,
Polygonum tinctoria, Isatis tinctoria and other plants.
Scutellarein is a yellow crystalline substance obtained by heating
Scutellarin, occuring in many Scutellaria species, with potassium
hydrate. Its metallic derivatives are very similar to those of gossy-
petin. Like the compounds of the flavone group, scutellarein and
gossypetin still contain a carbonyl group and a cyclic oxide oxygen.
Indigo also contains carbonyl groups but in place of the oxide
Oxygen, it contains nitrogen, still leaving the compound heterocyclic.
Brazilin obtained from Brazil wood and haematoxylin obtained
from the wood of Haematoxylum campechianum, do not contain a
carbonyl group. When crystallized from alcohol brazilin and haema-
toxylin are colorless crystalline substances, which rapidly become
red, undergoing oxidation. From the solutions of these two sub-
stances in caustic alkali, which rapidly become brown in contact
with the air, brazilein and haematein are obtained. Brazilein and
haematein are red crystalline substances which are products of oxid-
ation of brazilin and haematoxylin. These two compounds again
36
contain a carbonyl group. They as well as their products of oxid-
ation, brazilein and haematein form colored metallic derivatives
which are violet-red and sometimes even blue. The esters and ethers
of the colorless brazilin and haematoxylin are also colorless while
the esters and ethers of the red brazilein and haematein are yellow.
Although the woods from which these dyestuffs are obtained com-
mercially contain only brazilin and haematoxylin, from the ease
with which these substances can be oxidized to the more highly
colored brazilein and haematein, one might readily suspect the
presence of these latter compounds acting as plant pigments in other
parts of the plant.
Berberine, one of the few colored alkaloids and the Only alkaloid
used as a commercial dyestuff, is a yellowish-brown crystalline sub-
stance found in a large number of plants. Its relation to the other
dyestuffs, in being able to refer it to a similar hydrocarbon, has
already been spoken of. &
Ellagic acid is the only dyestuff under this degree of Saturation
which must be referred to an entirely different hydrocarbon from
the rest of the compounds, viz. diphenylenemethane. This can be
prepared from ellagic acid. Ellagic acid is a yellow crystalline sub-
stance ocurring very widely in nature as ellagitannic acid. Its com-
pounds with the metals are yellow. A solution of ellagic acid is
turned green and then blue-black by the addition of ferric chloride.
CnH2n-18 to CnH2n-36.
The compounds under the remaining degrees of saturation are
only few in number and have been studied but little. They will be
considered together.
Two quinones are known belonging to the degree of saturation
CnH2n-1.s, viz. fluoranthenequinone and 3-phenylnaphthoguinone.
They are obtained by the oxidation of the hydrocarbons fluoranthene
and 3-phenylnaphthalene to which they have been referred. They are
crystalline substances, fluoranthenequinone being red and A-phenyl-
naphthoguinone, yellow. Upon reduction both yield colorless hydro-
quinones. Phenylnaphtylquinhydrone, a blue crystalline substance
is obtained upon the incomplete reduction of 8 phenylnaphtoguinone.
The hydroxyphenylnaphthoguinone, the colorless hydroxyphenyl-
naphthohydroquinone and the blue hydroxyphenylnaphthoguinby-
37
drone have also been prepared. The metallic derivatives of the
hydroxyphenylnaphthoguinone are brown.
Pyrenequinone belonging to the degree of Saturation CnH2n-20
is obtained in the form of red crystals, by the oxidation of the
tetracyclic hydrocarbon pyrene. It is curious to note that the two
C=O groups are in different, widely separated cycles.

Its corresponding hydropyrenequinone is described as having a .
yellow color. Inasmuch as this is the only hydroquinone which is
colored, the purity of the substance described may be questioned.
The only other quinone belonging to this degree of saturation
is 1, 3, diphenylbenzoquinone, which is a red crystalline substance.
No hydroxy derivative of this compound is known.
Four quinones are known belonging to the degree of saturation
CnH2n-22. Chrysoquinone is obtained as orange-red crystals by the
oxidation of the hydrocarbon chrysene to which it has been referred.
Naphthanthraquinone, is a yellow crystalline substance which has been
referred to the known hydrocarbon naphthanthracene. There are two
known quinones referrable to the hydrocarbon naphthacene, viz.
naphthacenequinone and naphthacenediguinone. The latter is ob-
tained by the oxidation of the dihydroxy derivative of naphthacene-
quinone. Only one hydroquinone corresponding to these quinones
is known viz. hydrochrysoquinone. The quinhydrons have not been
prepared. af
Under the degree of saturation CnH2n-24, 2-naphthyl-naphthogui-
none, 1, 4, and di-2-naphthodiquinone can be referred to the same
hydrocarbon dinaphthyl from which they also can be prepared by
38
direct oxidation. Hydroquinones or quinhydrones of these com-
pounds are unknown. A monohydroxy derivative of 2-naphthylnaph-
thoguinone and a dihydroxy derivative of di-2-naphthodiquinone can
readily be prepared by the oxidation of the corresponding quinone
with dilute caustic alkali.
By heating 1, 2, 3-naphthoguinone belonging to the degree of
saturation CnH2n-10, with sulphuric acid, a binaphthyldiguinhydrone
belonging to this degree of saturation is obtained. This is a blue-
black powder which upon oxidation yields a yellow dinaphthyldigui-
none and upon reduction a colorless dinaphthyldihydroquinone.
There are known, furthermore, under this same degree of satura-
tion, the hydroxy derivatives of two quinones which are unknown.
These compounds are called ethylidene-3-dihydroxy-2-naphthoguinone
and isoamylidene-a-dihydroxy-naphthoguinone. They are yellow sub-
stances, the former of which is obtained by the condensation of
2-hydroxy-a-naphthoguinone with ethaldehyde and the latter by the
condensation of 2-hydroxy-a-naphthoguinone with isovaleric aldehyde.
Corresponding reduction products have not been obtained.
. Under the degree of saturation CnH2n-26, two quinones are
known. The first called 2-benzhydrylnaphthoguinone, 1, 4, is a
diphenylmethyl derivative of naphthoguinone, 1, 4, and the other is
a diphenylmethyl derivative of ortho naphthoguinone. The former is
a yellow substance which yields a yellowish-red dihydroxyderivative.
Picenequinone and crackenequinone both of which are red sub-
stances, belonging to the degree of saturation CnH2n-2s are obtained
by the oxidation of the hydrocarbons picene and crackene. Crackene-
quinone yields a reduction product which has undoubtedly not been
obtained in a pure form, judging from the color which is ascribed to it.
There are no quinones known having the degree of saturation
CnH2n-32, but the dihydroxy derivative of benzylidenedinaphthogui-
none has been prepared. This a yellow compound, the disodium
derivative of which is a dark carmine red powder.
The degree of saturation CnH2n-36 contains the 1, 4, bis-benz-
hydrylquinone, 2, 5, which can be regarded as benzoquinone in which
two hydrogen atoms in para position are substituted by two
diphenylmethyl radicles. This is a yellow compound which upon
reduction yields the corresponding well characterized hydro-
Quinone.
39
Botanical Classification.
In order to compare the behavior of flower pigments with the
general behavior of quinones and hydroquinones on the basis of the
quinhydrone hypothesis of pigmentation, tests were made upon a
large number of flowers. The results obtained, together with the
observations, recorded in literature, and made on flowers by other
authors with ut the knowledge of the quinhydrone hypothesis, are
- given in the following botanical classification in which the different
plants examined are arranged according to families. Those flowers
marked with an asterisk were collected with permission of Professor
Trelea, e, Director of the Missouri Botanical Garden.
As has been previously stated, the striking characteristic of the
colored quinhydrones is the fact that they will dissolve in the
ordinary solvents to form almost colorless or slightly yellow solu-
tions. Upon evaporation these solutions again yield the colored
quinhydrones. As can be seen from the accompanying tables a large
proportion of the red and blue flowers examined, yeld an almost
colorless solution when extracted with alcohol. In the majority of
cases, when this alcoholic solution is allowed to evaporate, a blue
or red residue is obtained. This colored residue will again dissolve
in organic solvents forming a colorless solution.
On the other hand all yellow flowers examined, witho t exception,
give an intense yellow solution with alcohol from which a yellow
residue is obtained. The fact that mºny red and blue flowers yield
colorless solutions when extracted with alcohol, has been known for
some time, 4849 but it was attributed to a supposed deoxid zing
power of the alcohol.
However, the red pigments of all flowers do not behave like
quinhydrones towards solvents. Thus for example, the red flowers of
Celosia cristata (Amarantaceae) are gradually extra ted by alcohol
forming a yellow solution. Upon evaporation a yellow residue is
formed. These as well as other flowers may have pigments which
are not of a quinone nature, for it is by no means to be supposed
that all flowers have as pigments the compounds previously con-
sidered. Yet the behavior of the pig ment in Celosia cristata can be
explained on the basis of these compounds. It is known that mono
hydroxyquinones are yellow while their metallic derivatives are red.
48 Elsner—Chem. Centralbl., 3, p. 572.
49 Marquart—Arch, d. Pharm., 56, p. 250.
40
Inasmuch as the alcoholic solution of these flowers is strongly acid
to litmus, it can readily be sten, if these flowers contained such
a red derivative, how a yellow residue would be obtained in the
presence of the acid or acid salt. If, therefore, this free ac'd were
neutralized by the addition of a few drops of a very dilute solution
of caustic potash to the alcoholic solution of the pigment a red
residue should be obtained. A red residue is actually obtained by
evaporating the alcoholic solution from the flowers of Celosia
cristata, previously neutralized with caustic alkali. Furthermore
the yellow residue from these flowers also turns red upon the addi-
tion of caustic potash.
In those cases in which a blue or red flower gives a yellow
alcoholic residue, the extraction of the pigment takes place very
slowly and the alcoholic solution is at first colored red which color
gradually disappears leaving a yellow solution. In those cases in
which a blue residue is obtained, the extraction takes place very
readily with the formation of a colorless solution.
The blue flowers of Myosotis species (Boragineae) blossom yellow at
first then gradually change to blue. When these blue flowers are ex-
tracted with alcohol, a yellow solution is gradually formed, which has
a faint acid reaction and leaves a yellow residue upon evaporation.
If, however, a drop or two of highly diluted caustic potash solution
be added to the alcoholic solution which is then allowed to evaporate,
a blue residue is obtained. In the same way, the yellow residue
first obtained turns blue or purple by the addition of dilute caustic
alkali.
From the examination of a large number of flowers Vogel 50
drew the general c nelusion that the alcoholic solutions of the pig-
ments from red flowers are always strongly acid when tested with
Jitmus paper. Blue flowers on the other hard, have in many cases
a neutral reaction or, if acid, are only faintly so. The colorless
alcoholic solutions of some blue flowers upon evaporat on leave a red
residue instead of a blue one. Thus there results upon the evapora-
tion of the colorless alcoholic solution of the pigment from the purple
flowers of Lagerstroemia indica (Lythrarieae) and Monarda didyma
(Labiatae) a red residue. By the careful addition of very dilute
ammonia or caustic alkali to the colorless alcoholic solution which
50 Sitzber. d. Acad., Muenchen, 1879, p. 19.
41
is slightly acid to litmus thereby neutralizing the free acid or acid
salts, the blue or purple color of the original flower is again ob-
tained.
These behaviors of the different flowers can readily be explained
when it is remembered that the metallic derivatives of the quin-
hydrones and hydroxy-quinones are blue or purple but in the pre-
sence of acids become red. Attention should also be called to the
fact that the red residues from the alcoholic solutions of many red
flowers are turned blue or purple by the addition of ammonia or a
very dilute alkali, and the blue residues from the blue flowers, or the
blue flowers themselves, are turned, red with hydrochloric acid. If
too strong an alkali is used the residue is turned green. Thus the
residue from the red geranium flowers can readily be turned to blue
by the addition of ammonia. Several red species of Salvia (Labiatae)
when held in 1he vapor of ammonia, turn to a blue which is of
almost identically the same shade as that of such species of Salvia
as are naturally blue.
Again, from the red flowers of Lobelia cardinalis (Campanulaceae)
a colorless solution with alcohol is obtained which yields a red
residue. This turns blue by the addition of caustic alkali solution
or by holding it in the vapors of ammonia.
In some cases, therefore, the blue and red species of the same
genus, are probably due to the same pigment the red being due to
the presence of neutral or acid salts or even free acids.
A more striking illustration of the contention that a blue pig-
ment is oftentimes the metallic derivative, under neutral conditions,
of a red pigment, is found in the case of the flowers of Centaurea
cyanus (Compositae). 95 percent alcohol extracts only a part of
the blue pigment of these flowers, which seems to be only sparingly
soluble in alcohol, resulting in a colorless solution which has a
neutral reaction. The flowers do not appreciably change in color.
Upon the evaporation of this solution a blue residue was obtained.
Upon the evaporation of a second portion after several months
standing a red residue resulted. The alcoholic liquid was now slightly
acid. Stein 51 has found considerable quantities of calcium in these
flowers.
51 Journ, prakt. Chem., 89, p. 495.
42
*
Another characteristic of the quinhydrones is the fact that they
are very readily reduced to the colorless hydroquinones which in
turn readily absorb oxygen resulting in the reproduction of the
colored compound. Many red and blue flowers, especially those
which give the quinhydrone test (colorless solution in alcohol), are
readily decolorized when held in an atmosphere containing a small
percent of sulphur dioxide.
Thus the purple alcoholic residue from the flowers of the purple
pansy (Violaceae) becomes colorless when held in an atmosphere of
sulphur dioxide but regains the purple color gradually when allowed
to stand in the air. In the presence of moisture the restored color
is red instead of purple, due to the fact that some of the sulphur
dioxide is retained by the moisture and the resulting acid turns the
purple residue to red. None of the yellow flowers examined, are at
all affected by even strong sulphur dioxide vapors.
Some flowers contain pigments of more than one color. For
example the purple-red flowers of Dahlia variabilis (Compositae)
contain a yellow and a red pigment. If these flowers are extracted
with alcohol for some time, a bright yellowish-red solution is ob-
tained which upon evaporation gives a dark red residue. If how-
ever, the flowers are allowed to stand in contact with the alcohol
for only a few minutes and the alcoholic solution then poured off, a
light yellow solution is obtained which yields a dark red residue.
Upon extraction with a second portion of alcohol, a bright yellow
solution is obtained which yields a yellowish-red residue.
Color of Color Of Color of
Observer. flower. alc. Sol. residue.
AMARANTACEAE.
*Celosia cristata.................. Brandel red yellow yellow
& 4 “ *................. Vogel red
*Celosia plumosa................. Brandel red yellow yellow
AMARYLLIDEAE.
Leucojum Vernum ”............ Stein
APOCYNACEAE.
Winca minor?..................... Marquart blue
( [. “ ”..................... Vogel blue
* Alcoholic solution is strongly acid (Sitzb. d. Acad. München, 1879, p. 19.)
2 Contains glucoside rutin which yields quercetin (Journ, pr. Chem., 85, p. 351.)
8 Aqueous solution turned lilac with boric acid (Arch. d. Pharm. 56, p. 249.)
16 Alcohole solution has faint acid reaction (Sitzb. d. Acad., München, 1879,
p. 19.
43
Color of Color of Color of
Observer. flower. alc. Sol. residue.
AROIDEAE.
Arum divaricatum 5.......... ....Marquart brown
Arum dracunculus, L.6.........Marquart brown
ARISTOLOCHIACEAE.
Aristolochia glauca 7......... ....Marquart brown
ASCLEPIADEAE.
Asclepias tuberosa 8......... .....Marquart Orange
Asclepias currasa vica. 9..........Marquart Orange
BORAGINEAE. -
Anchusa officinalis 10............. Hunefeld
Borago officinalis 19.............. Hunefeld
& 4 * { *.............. Vogel blue
& 4 “ *.............. Vogel blue
& 4 & 4 *............ ..Vogel white
Cynoglossum officinale 10...... Hunefeld blue colorless
14 ...... Vogel blue.
Cynoglossum omphaſod. 10...Hunefeld
Echium vulgare!"................. Elsner red decolorized red
6 & “ 17 ........* * * * * * * * * * Vogel blue
& 4 “ *................. Hunefeld
Echium pyrenaicum 19........... Hunefeld
*Heliotropus peruvianum, L...Brandel blue yellow light blue
& 4 & & 20Vogel blue
Myosotis palustris, L...........Brandel blue yellow yellow
& 4 { { “ 21......Wogel blue
Myosotis versicolor??....... ....Marquart blue
Nonea TOSea”....................... Marquart violet
15...Hunefeld
Pulmonaria angustifolia 24...Marquart red
Pullmonaria officinalis 24....... Marquart red
5
6
7
Color due to violet pigment and chlorophyll (Arch. d. Pharm. 56, p. 258).
Arch. d. Pharm. 56, p. 258.
Color due to chlorophyll and a blue pigment reddened by acid (Arch. d.
Pharm. 56, p. 258).
8
9
10
11
12
1 3
• 14
} 5
16
17
Acad.
18
20
21
Contains a yellow and a red pigment (Arch. d. Pharm. 56, p. 257).
Contains yellow and red pigment (Arch. d. Pharm. 56, p. 257).
Journ. f. prakt. Chem. 9, p. 217.
Color not changed by ammonia (Sitzb. d. Acad. München 1879, I, p. 17).
Alcoholic solution is acid (Sitzb. d. Acad. München 1879, p. 19
Alcoholic solution has acid reaction (Sitzb. d. Acad. München 1879, p. 19).
Has faint acid reaction (Sitzb. d. Acad. München 1879, p. 19)
Yields colorless solution with turpentine (Journ. pr. Chem. 16, p. 68).
7 ()
Yellow precipitate with lead acetate (Chem. Centralh. 3, p. 570)
Has faint acid reaction. Flowers are red then orange to bitte (Sitzb. d.
München 1879, p. 19).
and 19. Journ. f. prakt. Chem. 9, p. 233.
Has faint acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
and 22. Flowers are first yellow then change to blue (Arch. d. Pharm. 56,
p. 26(
23
24
)
).
Solution turned red with boric acid (Arch. d. Pharm. 56, p. 263).
Changes to blue upon fading (Arch. d. Pharm. 56, p. 263.)
#
44
Color of Color of
Observer. flower. alc. Sol.
CACTEAE.
Cactus phyllanthus 25...........Buchner blue-red colorless
Cactus flagelliformis”5..........Buchner blue-red colorless
Cactus speciosus?"................Vogel red colorless
CALYCANTHACEAE.
Calycanthus floridus 27..........Marquart brown
CAMPANULACEAE.
Campanula ranunculoides 28.Vogel violet
* { ( & 29. Vogel violet
Campanula glomerata”.......Vogel blue
Campanula rotundifolia 29....Wogel blue
Campanula grandiflora 80.....Hunefeld
Campanula persicifolia *1 ...... Vogel blue
Campanula pyramydalis B1 ...Vogel blue
Lobelia erinus *....................Vogel blue
* Lobelia cardinalis, L............Brandel red yellow
*Lobelia Syphilitica........... .....Brandel blue colorless
CAPPARIDEAE.
Capparis Spinosa. 38...............Rochleder yellow
CAPRIFOLIACEAE.
Sambucus migra *................. Hunefeld white
Viburnum opulus, var. rosea ºf Marquart white
|Wiburnum opulus 86 ..............Filhol white
CARYOPHYLLACEAE.
Dianthus caryophyllus..........Brandel red pink
Dianthus species 87................ Elsner red pink
Dianthus cartham.88.............Vogel red
Dianthus carthusianorum39..Vogel red
Lychnis chalcedonia. 40..........Elsner red colorless
4 & ( &
Color of
residue.
blue
blue
red
red
blue
red
red
red
41..........Vogel red
25 Rººg § turned green with alkalies and red again with acids (Chem. Cent-
ralbl. 7, p.
26 Ann. d. Chem. 5, p. 205.
27 Cross section shows middle layer of chlorophyll and two outer layers of
violet pigment (Arch. d. Pharm. 56, p. 258).
28 Turned green by ammonia (Sitzber. d. Acad. Muenchen 1870, I, p. 17).
Acad. Muenchen 1879,
D. *
30 Journ. f. prakt. Chem. 9, p. 217
1.) Alcoholic soluti, ºn has neutral reaction (Sitzb. d.
31, Alcoholic solution has faint acid reaction (Sitzb. d. Acad. Muenchen, 1879,
p. 19)
33"Buds contain quercetin glucoside (Chem. Centralbl. 30, p. 166).
84 Contains copper (Journ. f. prakt. Chem. 16, p. 84)
35 Changed to red on wilting (Arch. d. Pharm. 56, p. 262).
86 Changed to yellow with am monia (Compt, rend. 39,
p. 194).
i; Alcoholic solution has neutral reaction (Sitzb. d. Acad. Muenchen 1879,
37 Aqueous solution gives blue green prec. with lead acetate and violet precipi-
tate with zinc chloride (Chem. Centralbl. 3. p. 570).
38 Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
p. 19).
40 Chem. Centralbl. 3, p. 572.
41 Same as 39
º Alcoholic solution has strong acid reaction (Sitzb. d. Acad. Muenchen 1879,
45
Color of Color of
Observer. flower. alc. Sol.
CARYOPHYLLACEAE.
Lychnis chalcedonia 42..........Hunefeld red
& & 4 & 48..........Marquart red
Saponaria officinalis............ Brandel rose colorless
Silene armeria 48....................Marquart red
& 4 & 4 *........... ........Vogel red
CHENOPODIACEAE.
Artriplex hortensis 45............Hunefeld red
. “ “ 46. .......... Schnetzler red
CoMPOSITAE.
Achillea millefolium 47...........Wogel I’OSé
Arctotis grandiflora 48..........Marquart orange
Anthemis tinctoria 47............
& 4 “ 49........... .Vogel white
& 4 “ 50............ Vogel yellow
Aster.......... tº tº ſº dº ſº e º $ tº a tº e º 'º $ tº e º ºs º º º ºs e º 'º e & Brandel blue yellow
“ ................ & © tº º e º 'º e º is is e º a º e º ſº e g º ºs Brandel dark blue colorless
“ ...................................... Brandel red yellow
“. ..................................... .Brandel white yellow
“ ...................................... Brandel purple yellow
Aster, wild.................... * * * e º ſº e º 'º Brandel white colorless
& 4 “ ..................... iº & sº tº e º ſº tº Brandel blue colorless
Asterºl............ tº e º tº e º 'º tº tº ſe - tº ſº tº E tº g tº e º e is Elsner red
Aster chinensis”................... Vogel violet
& & “ ”................... Vogel blue
Aster movaeangelaeº?....... ...Vogel red
Aster tenellaº...................... Vogel violet,
Bellis perennisº.................... Hlasiwetz
Calendula, officinalis 55.......... ..Wirth
& 6 *6 & 56...........Kirchner
& 4 ‘‘ 48........... Marquart orange
& & ( & *"........... Hunefeld orange
& 4 ( & 58........... Schnetzler yellow
Calliopsis bicolor #8...............Marquart yellow
42 Journ. f. prakt. Chem. 16, p.
48 Aqueous solution is turned pu
73.
is formed (Arch. d. Pharm, 56, p. 252)
44 Same as 89.
Arch. d. Pharm. 56, p. 257.
*
55 Contains esters of cholesterin
|). 2:5)
Journ. f. prakt. Chem. 16, p. 74
Aqueous solution turned green with borax (Jahresb. u. d. Fortsch. d. Chem.
p. 925).
Solution has acid reactign. (Sitzb. d. Adad. Muenchen 1879, p. 19).
and a hy
Color of
residue.
pink
pink
purple
red
yellow
purple
yellow
yellow
decolor. purple-red
ple red with zinc chloride but no precipitate
2
Turned yellow by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
Solution gives green prec. with lead acetate (Chem. Centralbl.
Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
Turned green by ammonia (Sitzb. d. Acad. Muenchen 1870, 1, p. 17).
Contains quercetin (Ann. d. Chem. 112, p. 96.)
p. 570).
drocarbon (Bot. Centralbl. Beih. 3,
Contains cholestrin esters (Bot. Centralbl. 52, p. 229).
57 Contains iron and man 2 anese (Journ. pr. Chem. 16, p. 84).
58. Not changed by borax solution (Jahresb. ii. d. Fortschr, d. Chem. 1877,
p. 926).
46
Color of Color of Color of
Observer. flower. alc. Sol. residue.
COMPOSITAE.
*Callistephus chimensis............Brandel rose colorless pink
* , t ( 4 & ............Brandel light blue colorless pink
* * & & C ............ Brandel blue colorless blue
* { % & 4 ............ Brandel crimson colorless red
*Centaurea gymnocarpa......... Brandel blue colorless yellow
Centaurea cyanus..................Brandel blue colorless pink
Centaurea cyanus 59..............Hunefeld
( & “ 60..............Stein blue
{ % “ 91..............Nietzki blue
{ { “ 62 ....... .......Vogel violet
Centaurea jacea. 9°.................Vogel red
Centaurea Scabiosa. 68............Wogel purple red
Cichorium intybus.................Brandel blue colorless blue
Cichorium intybus 94.............Wogel blue
£ 6 “ 65.............Nietzki blue
( ( “ 66.............Vogel blue
Cineraria cruenta 67...............Marquart blue colorless blue
Carduus species 98............... ...Elsner red decolor. red
Chrysanthemum vulgare 69... Filhol white
Coreopsis bicolor:70....... tº gº tº e º 'º º º Vogel yellow
Cuphea Vinosa 71........... ........Vogel red-violet
Cuphea miniata'7*.......... ........Vogel red
Cosmos................................. .Brandel purple pink purple
Dahlia variabilis...................Brandel crimson yellow red
( & & 4 * * * * * * c e º 'º º tº .......Brandel red yellow red
( & “ ............... ....Brandel yellow yellow yellow
& 4 “ ..... © e º & © e º ſº s e º e º ºs Brandel white yellow yellow
( & “ ................... Brandel purple-red light red dark red
Dahlia 78 ......... .......................Elsner red colorless dark violet
Gaza1‘ria ringens 74....... .........Marquart
Helianthus annuus 75............Fremy yellow yellow yellow
*Helichrysum monstrosum
luteum................... & © e º e º g º e º & ..Brandel yellow yellow yellow
* Helichrysum monstrosum &
Salmonosa..........................Brandel pink yellow yellow
59 Journ. pr. Chem. 9, p. 217).
60 Turned red with hydrochloric acid. Contains much calcium (Journ. pr.
Chem. 89, p. 495).
61 Contains glucoside (Arch. d. Pharm. 208, p 327).
62 Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
68 Solution has acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
64 Solution has faint reaction (Sitzb. d. Acad. Muenchen 1879. p. 19).
* Cºns glucoside which yields a product M. P. 250–255° (Arch. d. Pharm.
208, p. 327).
66 Turned green by ammonia (Sitzb. d. Acad. Muenchen 1870, p. 17).
67 Solution is tºurned lilac with boric acid (Arch. d. Pharm. 56, p. 250)
68 Solution gives brown prec. with zinc chloride, greenish prec. with lead
acetate (Chenn. Centralbl. 3, p. 570).
69 Turned yellow by ammonia (Compt. rend. 39, p. 194).
70 Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
71 Turned blue b y ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 17).
72 Solution has strong acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
78 Solution gives dark green prec. with lead acetate (Chem. Centralbl. 3, p. 572).
74 Arch. d. Pharm. 56, p. 258).
75 Journ. de Pharm. (3) 25, p. 249.
9
47
Color of Color of Color of
Observed. flower. alc. sol. residue.
COMPOSITE.
*Helichrysum monstrosum
TOSéll II] ... . . . . . . . . . . . . . . . . . . . . . ........Brandel pink colorless red .
*Helichrysum monstrosum
roseum (disk flor.)............. Brandel yellow yellow yellow
*Helichrysum monstrosum
purpurea.............................Brandel purple pink purple
Helichrysum bracteatum 76...Rosoll yellow
Helichrysum arenarium 76.....Rosoll yellow
Serratula species 77................ Elsner red colorless red
Tanacetum vulgare?” ........... Hunefeld
{{ “ 79........... Leppig yellow
*Zinnia elegans (scarlat gem). Brandel red yellow yellow
* & 4 é & Salmonea *
rosea...........Brandel red yellow pink
# ( & { % carminea........ Brandel carmine yellow purple
* { { “ aurea............. Brandel yellow yellow yellow
* {{ & & purpu Tea........ Brandel purple yellow brown
Zinnia elegans 89.................... Vogel red
CONVOLVULACEAE.
Ipomoea purpurea, L........... Brandel purple colorless purple
Ipomoea mutabilis81 ............ Marquart blue
Convolvulus tricolor 82.......... Hunefeld
Convolvulus arvensis 88......... Vogel I’OSé
Convolyulus mauritianus 8+..Vogel blue
Convolvulus bicolor 85........... Vogel blue
Symphytum officinale.88........ Vogel red
CORNACEAE.
Cornus mascula 89................. Stein
CRUCIFERAE.
Cheiranthus Cheiris'7............. Marquart purple
& & ‘‘ 88.............Perkin yellow
Cheiranthus scoparius 89.......Marquart violet
Cheiranthus (Levkoy)90........ Elsner red decolorized violet
76 Contains helichrysin (Monatsh. f. Chem. 5, p. 94).
77 Chem. Centralbl. 3, p. 572.
78 Contains iron (Journ pr. Chem. 16, p. 84.
79 Contains tanecetin (Pharm. Ztschr, f. Russl. 21, p. 141, 169, 193).
80 Solution has strong acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
81 Flower was at first white (Arch. d. Pharm 56, p. 262).
82 Journ. f. prakt. Chem. 1:6, p. 69.
1. Alcoholic solution has strong acid reaction (Sitzb. d. Acad. Muenchen 1879,
. 19).
p 8 * Has faint acid reaction (Sitzb d. Acad Muenchen 1879, p. 19)
85 Has neutral reaction (Sitzb. d. Acad. Muenchen 1879, p 19).
sº Contains glucoside rutin which yields quercetin (Journ. f. pr. Chem. 85,
p. 350 l.
87 Contains yellow as well as purple pigment (Arch. d. Pharm. 56, p. 257).
88 Contains quercetin and isorhamnetin (Chem. News 74, p. 278).
89, Flowers are at first yellow, gradually becoming orange then violet (Arch.
d. Pharm. 56, p. 260.
90 Aqueous solution gives blue prec., with lead acetate and violet prec. With
zinc chloride (Chem. Centralbl. 3, p. 570).
48
COlor of Color of Color of
Observer. flower. alc. Sol. residue.
CRUCIFERAE.
Erysinum perofsk 91..............Vogel yellow
Fumaria officinalis 92............ Vogel I’OSé
Hesperis matronalis 98..........Vogel violet
Iberis umbellata 94................ Elsner red colorless violet
Iber is violacea 95............ .......Vogel blue
ERICAEAE. *
Azalea pontica. 9°................... Marquart yellow yellow
{ % § { *"................... Vogel I’OSé
Rhododendron arboreum 98..Marquart dark red
GENTIANEAE. *
Gentiana acaulis 99................Marquart blue green
GERANIACEAE.
Geranium........... ................... Brandel light red yellow red
Geranium........... .................... Brandel dark red-light red dark red
Geranium sanguineum'......... Elsner red light red red
& 6 { % *......... Marquart red
Geranium robertianum 8....... .Vogel red
Impatiens balsamina 1..........Elsner red
{ % ( & *......... .Vogel red
Trompaeolum majus............. Brandel red yellow red
( { “. .............Brandel yellow yellow yellow
Trompaeolum coccineum 8....Vogel red
* Pelargonium peltatum.......... Brandel dark red red dark red
* Pelargonium Zonale.............. Brandel red colorless red
* Pelargonium zonale Heter-
anthe................ .. & e º e º 'º e º e º ºs e g ..Brandel red pink red
Pelargonium species 4.......... ...Elsner red colorless red
Pelargonium zonale 5............Filhol red light red
Pelargonium inquinansº.......Filhol red light red
HYPERICINEAE. *
Hypericum perforatum 6.......Buchner red colorless red
91 Not changed by ammonia (Sitzb. d. Acad. Muenchen 1870, I, p. 1
92 Has strong acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
98 H as acid reaction (Sitzb. d. Acad. Muenchen 1879, p. 19).
94, Aqueous solution gives green prec. with lead acetate and yellow prec. with
zinc chioride (Chem. Centralbl. 3, p. 570).
95 Turned green with ammonia (Sitzb. d Acad. Muenchen 1870, p. 17).
96 Arch. d. Pharm. 56, p. 248.
97 Alcoholic solution has strong acid reaction (Sitzb. d. Acad. Muenchen 1879,
7).
p. 19).
Strongly acid (Arch. d. Pharm. §3. p. 250).
: Arch. d. Pharm. 56, pp. 249, 259.
,, . " Aqueous solution gives yellow precipitate with lead acetate (Chem. Centralbl.
3, P; §ous solution gives lilac precipitate with zinc chloride (Arch. d. Pharm.
56, *Atºlls solution has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879,
D. *hem. Centralbl. 3, p. 572. q
5 Red aqueous solution is turned blue by ammonia (Compt. rend. 39, p. 196).
6 Residue turned green with alkalies (Berz. Jahresb. 11, p. 279).
~3
49
p Color of Color of Color of
Observer' flower. alc. Sol. residue,
IRIDEAE. - | ' ' ' ' ||
Crobus mnesiaeus’........'......Marquart- yellow . . . . ( .
Crocus Sativus 8..................... Schueler . . . . . . . ; : º
Gladiolus species 9................. Elsner red colorless blue
Iris pumila 1"......................... Marquart violet colorless violet
Iris pumila purp. 11............... |Hunefeld . . . ' * \
Iris hor:tensis 1*..............'....... Hunefeld blue amethyst
( 4 ( & *..................... Hunefeld % }
Iris hispanica 1°..................... Hunefeld blue amethyst . . .
Ixia, crocatº, "...................'... Marquart Orange {
LABIATAE. * } !
Ajugal reptans”...... ..... p & 8 & tº it is & Marquart blue colorless green
& C “ "..... .............. Vogel blue J.
*Cedronella cana..................... Brandel spotted , \ .
* with red colorless colorless
Dracocephalum altaicum 17...Marquart blue blue . . . . | | | }.
{ { “ 18 Vogel lilac e
Hyssopus officinalis 19.......... .Vogel blue º
{ % ( & 30........... Vogel white t
& 4 ** 20........... Vogel I'ed }
( & * { *........... Vogel blue , , , ,
Jamium purpureum?!........... Vogel red { .
Lamium inaculatum **.......... Vogel red
*I/ophanthes anisatus............ Brandel blue colorless colorles
Monarda didyma.................. Brandel purple colorless red
Monarda fistulosa ................ Brandel purple colorless red
Monardº, coccinea. 38.............. Elsner red colorless red
Monard: eczırlate**.............. Belhomme searlet . . . .
Nepeta cataria *................... Hunefeld º
* Physostigezi, Virginiana......... Brandel purple colorless yellow
* Premanthemum muticum...... Brandel purple
.*
7 Alcoholic residue soluble in water (Arch. d. Pharm. 56, p. 253).
8 Contains esters of phytosterin (Bot. ('entralbl. S7. * *
9 Solution gives red precipitate with zinc chloride and
acetate (Chem. Centralbl. 3, p. 57 ()). g *
ith acids, blue with little all ali,
1 ()
Plla, l'Inn
1 1
Turns red w
. . , 6, p. 244)
12 Journ, pr. ('hem. 9, p
(#ives bluish-retl solutio
t
as a 2 & Jº e
* * — ,s's
º with ether-alcohol (Jouri. pr. Chenn. 16, p. 70). ,
23:}
spots colorless colorless
|
p. 1:52). t
dark green with lead
green with excess (Arch.'d:"
•
| * †
13 ('ontains iron and manganese (Journ. Dr. Chenn. I 6, p. S4).
14 Contains a red and a yellow pigment. (A reh. d. Pharm. 56, p. 257). •
15 Arch, d. Pharm, 56, p. 253. . º
16 Turned green by alm monia. (Sitzb, d. A catl. Muenchen 187 (), I, p. 17). . .
17 Aqueous solution turned lilac with boric acid (Arch. d. I’harm. 56, p. 24.S).
is , urned light green by tum monia (Sitzb. (l. Acad. Muenchen, 1 S7 (). I, p. 17).
19 Alcoholic solution has neutral reaction (Sitzb. d. Aca, i, Muenchen, 1879,
p. 19). º *
20 Not changed by a munonia. (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
2 I Sanne as 26. J. g ! . . . . $2. 1
22 Alcoholic solution has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879, ''
p. 19). * * 3 - --&
as Solution gives red precipitate with lead acetate (Chem. Centrally]. 3, ..] . (573), ;
2 b (on tains earlmine identical with earmine from co shineal (Qomipt. l'en't] ... +3,
382). e *
p. 382) 217. . . . . . . . . li i , , , ; ; ; ; ; a tº i t . . . . . . * *
... 25 Journ, pr. Chem, 9, p.
Color of ('Olor of Color of
Observer. flo Wel'. tulc. 80l. residue.
LABIATAE. *
*Salvia splendens........ ............Brandel red colorless red
( & “ 26.................Filhol red
*Salvia memorosa 20............ ...Brandel blue colorless blue ,
*Salvia Pitcheri...................... Brandel light blue colorless yellow
*Salvia azurea .,,.....................Brandel light blue colorless yellow
*Salvia coccinea.................. ....Brandel red faint pink deep red
Salvia variegata 27................ Hunefeld
Salvia cardinalis 28................ Vogel red
Salvia officinalis”9................ Vogel blue
Salvia nobilis 89..................... Vogel blue
Salvia pratensis 31................. Vogel blue
* Scuttelaria altissima............. Brandel light blue colorless blue
Stachys palustris 8°............... Vogel red
Stachys sylvatica 89............ ..Vogel red
Thymus serphyllium 82..........Vogel red
LEGUMINOSAE.
Cassia ligustrina 88................ Marquart yellow yellow
*Clitoria ternatea ................... Brandel blue blue blue
Coronilla varia, 84.................. Vogel violet
& 4 “ 8*.................. Vogel red
Butea frondosa. 30................ ... Hummel
Hedysarum coronarium 87....Elsner red colorless violet
Lathyrus odoratus............... Brandel purple colorless purple
& 6 " ..…. Brandel pink colorless pink
Lathyrus latifolius 88............ Elsner red colorless violet
Lathyrus tingitanus 89..........Marquart red
Lupinus Cruickshankii 40....... Marquart blue
Lupinus mutabilis 41............. Marquart red
Lotus corniculatus 42............ Vogel yellow
( & ( 4 48 ............ Vogel yellow
26 Turned blue by
alkalies (Compt. rend. 43, p. 545).
Journ. pr. Chem. 9, p 217.
Turned blue by ammonia (Sitzb. d. Acad. Muenchen, 1870, I. p. 17).
Not changed by ammonia (Sitzb., d. Acad. Muenchen, 1870, I, p. 17):
30. Alcoholic solution has neutral reaction (Sitzb. d. Acad. Muenchen, 1879,
1. Alcoholic solution has faintly acid reaction (Sitz b. d. Acad. Muenchen, 1879,
p. I $*).
1. Alcoholic solution has strong acid reaction (Sitzb, d. Acad. Muenchen, 1879,
...rement difficultly soluble in absol. alcohol and ether (Arch. d. Pharm., 56,
I). 2 *
84. Not changed by ammonia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
85 Has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
36 Contains a glucoside (Ber. 1896, p. 658).
87 Chem. Centralbl. 8, p. 570)
98 'Solution gives orange prec. with zinc chloride and yellow prec. with lead
acetate (Cheºn. Centralbl. 3, p. 570).
... outſon gives purple prec. with zinc chloride (Arch. d. Pharm. 56,
I}. 25. * - i
sºlower. are at first white changeing to blue (Arch. d. 56,
p. º
41 Flowers are at first white changeing to red (Arch. d. Pharm. 56, p. 262),
42 Same as 34.
48 Solution has acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
Pharm.
‘51
Color of Color of Color of
Observer. flower. aic. 801. regidue.
LEGUMINOSAE.
Genista tinctoria, 44. ............... Hunefeld
Medicago Satiya 4*................ Vogel blue
Pisum sativum 4°.................. Vogel violet
Phaseolus multiflorus 47........ Vogel red
Podalyria australis 48........... Marquart blue green
Robinia, hispidia 49.............. ...Elsner red colorless violet
Robinia pseudacacia 50.......... Zwenger
Spartium scoparium 51.......... Hunefeld
Sophora japonica tº.............. Rochleder yellow
• { ‘‘ 58......... .....Schunck yellow
Trifolium platense, L........... Brandel red colorless yellow
Trifolium pratense 54............. Vogel red
Trifolium agrestis 47............. .Vogel red
Vicea faba Gº.,,.......................Marquart
LILIACEAE.
Allium nigrum 50...................Marquart black
Allium Schoenoprosº"...........Vogel light red
Fritillaria inlper. 58...............Hunefeld red
'Hemerovallis fulva 59.............Marquart orange
Hyacinthe 99..........................Hunefeld red and blue
Hyacinthus botryoides 61.. ...Stein blue
Lilium tigrinum splendens....Brandel orange yellow pink
Lilium candidum 9°......... ......Hunefeld
Scilla Sibirica. 98..................... Marquart blue colorless
Scilla amoena 94.................... Hunefeld
Scilla campanulata 94............ Hunefeld
Tulipa ovulus solis"............ Marquart red
Weratrum migrum 00..............Marquart brown
44 (on tains iroti (Journ. Dr. Chelm. 16, p. 84).
45, Solution has faint acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
46 Turned green by ammonia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
47 Solution has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
48 Arch. (l. I’harm. 56, p. 253.
49 Solution, gives blue-green prec. with lead acetate, red with zinc chloride
(Chem. Centra bl. 3, p. 572).
50 Contains glucoside robinine (Ann, Suppl. I, p. 257).
51 Contains iron (Journ. Dr. Chem. 16, p. 84).
52 (;ontains quercetin (Chem. Centralbl. 30, p. 166).
58 Contains glucoside rutin (Journ. Chem. Soc. 67, p. 30).
h4. Not chiunged by alm monia (Sitzb. d. Acad. Muenelmen, 1870, I, p. 17).
55 Arch. (l. Pharin. 56, p. 259.
56 Arch. d. Pharm. 56, p. 25.S.
57 Turned green by ammonia (Sitz b. 1. Acad. Muenchen, 1870. T, p. 17).
58 Contains red and yellow pigment. Turpentine dissolves out red pigtuent
forming colorless solution (Journ, pr. Chem. 16, p. 68).
9 Contains red, and yellow pigments (Arch. d. Pharm. 56, p. 257).
6. Turpentine dissolves pigments to colorless solution (Journ. pr. Chem. 16,
D. º º -
6 L Turned red with hydrochloric acid (Journ. pr. Chem. 89, p. 495).
62 Contains iron (Journ. f. prakt. Chem. 16, p. ).
63 Forms colorless solution with 40 p. c. alcohol (Arch. d. Pharm. 56, p. 247).
6 4 Journ. pr. Chem. 9, p. 21 7 ; 16, p. 84.
65 Cross section show 8 three la vers, in net. One is colorless, two outer ones blue
or retl (Arch. d. Pharm. 56, p. 256).
66 ("ontains a blue pigment, (Arch. d. Pharm 56, p. 258).
f 52
*.
Color of Color of Color ot
1 tº it; ; ; * * tº i t . . . . ) “t 's ' ) b ~ * .** - -
* , , is : ; ; , " , ; ; ; ' ' ' ' ' " : ... , ppsaliver. ſlower. alc, sol. residue,
Liº. " " "" ; o . . . . . . . . . . . . .
Linum perenne"7........ tº e º 'º e º q tº ...Marquart blue , . . . . .
“ , “ 68......... ........'...Vogël’, blue . . . . . . .
{ { “ 69........'..........Wögel “blue” . . . . . . . .
Linum Syriacum "...y. tº e º º º .Vbgel. 1}lue.’ ‘‘‘, ' ' ' ' '
| ' ". . . . . . . . • * : , , , , , , , , . . . , -
LOGANIACE.E. ! . . . . . . . . . . . . . . . . . . . . . . . .
Budleia globost 70....... ..........Marquart... yellow
LYTHRARIE.E. . . . . . . …
$ w tº * ~ : e & & } . tº * ..." * * * * * * * * * * * º - i .** 1. s i * †
LagerStroemia indiew...….....Brandel purple slightly pink red
MALVACEAE. • - ... . . . . . . . a * -
... a. i - 2. f : . * . . . . . - - } s: . - - * , \ * -
*Althaea rosea............. ...........Brandel “red slightly brown dark red
Althaea rosen Tº...................Elsner purple partly decoſ. purple red
{ { “ 72........ !..........Hanausek: “ . . . . . . . . . .
* & “ ”..................i.Glån …gred • * * * * * * * * * * * *º
{ { “ "*................... Vogel TOSé º +
{ { " *................... Vogel light violet . . . . --
{ { “ 75....................Vogel ...dark Violet . . . . . . . . . .
*Alloda hastate.......................Brandel......blue colorless blue
Gossypium herbaceum,79,.... i. Perkin ..... yellow . . . .
* Hibiscus Syriacus..................Brandel. ... purple colorless purple
* i & “. . .................. Brandel... white... .. colorless colorless
* { { “ ........... .......Brandel... . blue colorless blue
'#. Toša Simensis...........Brandel... purple pink purple
Hibiscus Syriacus 77............. ... Fremy ......blue... . . colorless blue
La Vatera trimestris 78...........Vogel .. rose ...
Malva rotundifolia................Brandel ... rose . . . colorless colorless
Malva Sylvestris ("................Elsner red colorless red
& C ( * "*................ Vogel rose - *
Malva rosea, 80....... * * * * * * * * * .......Hunefeld - - -
Malva rotundifolia 81 ............ Vogel l'OSČ - - --- - - - -
MYRTACE.E. . . . - -
Metrosideros lanceolatas?...Elsner red colorless red
"Metrosideros semperflorensséVogel red -
67 Arch. d. Pharm. 56, p. 249. – - -
68 Declorized by an monia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
1.) Alcoholic solution has neutral reaction (Sitzb. (l. A catl. Muenchen, 1879,
l). i \}). - : * ,
70 Alcoholic extract is soluble in water (Arch d. Pharm. 56, p. 253). -
71 º solution gives violet precipitate with zinc chloride, blue-green prec.
With lead acetate (Chem. Centralbl. 3, p. 570) - -
72 Iłot. Centrallyl. 25, p. 254.
73 Contains a glucoside (Bot Centralbl. 13eilleft 3, p , 292). -
74 Turned green by ammonia (Sitzb. d. Acud. Muenchen, 1 S7(), 1, p. 17).
75 Not changed by ammonia (Sitzb. d. Acad. Muenchen, 187 (), I, p. 17).
76 Contains glucoside which yields gossy petime (Journ. Chem. Soc., 1899, p. 8:25).
77 Journ. de Pharm. (3) 25, p. 249. - -
78 Turned blue by ammonia (Sitzb. d. Acad. Muenchen, , 1870] I, p. 17). .
79 (+reen prec. with lead acetate, red with zinc chloride (Chem. Centralbl. 3,
80 Contains iron (Jourti.) pr., Chem. 16, p. 84). . . . . . . . . . . . . . f ºv
81 Has stroug acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 10), . .
82 Chem. Centralbl. 3, p. 572. , , , … . . . . . . . . . :-
Sº Alcoholic solution has strong acid reaction (Sitzb, d, Acad. Muenchen, 1879,
1). 19). ; : " , ; . . . ; ; ; ; ; ; ; ; ; ' ' ' ' ' . . . . . . . . . . . i.; ; ; , . . . . . . . . . . . . .”
a 4
r
53
tº tº gº. observer. “º º 'ºiº
NYCTAGINACE.i. p
*Mirabilis jalapa.............. ........Brandel red slightly yellow yellow
# & K “ ..... * * * * * * g º is e º is s ...Brandel pink colorless yellow
* { { " ..................."...Brandel yellow yellow yellow
ONAGRARIE.E.
Gaura biennis 8+.................. ..Marquart white
Fuchsia procumbens, | tº s $ tº s
(Red part)................... .......Brandeſ red colorless purple
I'uchsia procumbens
(Purple part).......... * . . . . . . . . . . Brandel purple pink purple
Oenothera acaulis 8*.............. Marquart white
Oenothera speciosa, Nutt.85 Marquart white
Oenothera grºundiflora, 80.......Hunefeld . . . . . . .
Oenothern 87 .......................... Vogel yellow
ORCHIDE.E. * , , ; ,
Orchis vermus 38..................... Marquart, red .
Orchis coriophora, L.89........ Jº . . . . . . ."
OXALIDE.E. 4 * * * ;
Oxalis tetraphylla 99............. Vogel. ‘’’’’ i"Ose .
PAPAVERACE.E. i * * * * *
, Papa ver bracteatum”!......... Marquart dark red
Papa ver nudicaule 99............. Marquart yellow *
Papa ver' rhoeas” ................. Elsner red colorless red
& ‘‘ 94 ....... a e s e s is a s a e Filhol 1'ed *
& & “ ”................. Vogel red
Papa Ver somniferum 96 ......... Hunefeld red
C & { { 96 ......... Hunefeltl white
( & ( & 95 ......... Vogel red
Papal ver' burzerii.97.................Weiss yellow
'apel ver pyrenaicum 97 ..........Weiss orange-red
PLUMB.AGINE.E. #
*Ceratostigma plumba-
geneoides............................ Brandel blue slightly slightly
yellow pink
84. I'lowers change to retl upon fading (Arch. d. Pharm., 56, p. 262).
85 White flowers gradually change to red after having blosso med for a time
*
(l. Pharm. 56, p. 262).
(Arch.
86 Contains iron (Journ. f. pr. Claem. 16, p. 84).
87 Not changed by ammonia (Sitzb. (l. Acad. Muenchen, 187 (), I, p. 17).
$3 ).
88 Flowers become blue on fading ( Arch. d. Pharm. 56, p. 263)
89 Probably contains capronic acid (Compt. rend. 58, p. 639)
90 Turned blue by an monia (Sitz b. (l. Acad. Muenchen, 1s?0. I, p. 17).
9 L Alcoholic Solution has acid reaction (Arch. d. Pnarm 25
92 Alcoholic residue soluble in water (Arch. d. Pharm. 56, p. 250)
56, 1) 250
98 Aqueous solution gives violet precipitates with lead acetate and zinc chloride
(Chem. Centralbl. 3, p. 572).
94 Turned blue by alkalies (Compt., rend. 50, p. 545)
93 Alcoholic solution has strong acid reaction isitzi. d. Acad. Muenchen, 1879,
p. 19).
96 Contains iron (Journ. pr. Chem. T6, p. 84
). *
97 Contalus yellow crystalline pigment (Bot, Čentraibl. 21, p. 101),
Color of Color of Color of
Observer. flo Wer. alc. Sol. residue.
POLEMONIACE.E.
Polemonium coerul. grandiff. Hunefeld
Giglia aggregata 98...............Hunefeld
POLY GAL.E.E.
Polygala Vulgare”............... Hunefeld
Polygala amara 1.................,Vogel blue
PRIMULACE.E,
Anagallis al’vensis”..,........,...,Vogel red
Lysumachia numularia 8.......Vogel yellow
Primula veris+......................Hunefeld yellow
l{ANUNCULACE.E.
A comitum napellust ..............Vogel blue
Aconitum vulgare"...............Marquart blue green
Aquilegia vulgaris 7...............Hunefeld
Aquilegia Vulgaris 8...............Hunefeld
Aquilegia Speciosa 3.,,,,, .......,
Anemone hortensis?..............Filhol red
Anemone pavonina, 10............Filhol red
* Delphinium hybridum ...........Brandel blue colorless blue
Delphinium 11.......................... Elsner red colorless pale red
Delphinium discolor 12...........Hunefeld
Delphinium consolida 18........ Perkin blue
{ { ( & 14........Vogel blue
{ { © ( *......... Vogel blue
Delphinium formosum 14........ Vogel blue
& C ( & 15........ Vogel blue
Delphinium zalil 10................. Perkin yellow
Clematis integrifolia. "............ Hunefeld
& 4 . . . *............ Hunefeld
Nigella damascena 5..............Vogel blue
98
99
1
p. 19)
2
p. 19)
3
-i.
5
(
p. 19)
:
Journ. pr. Chenn. 9, p. 217.
Journ. pr. Chem. 9, p. 217.
Alcoholic solution has a faint acid reaction (Sitzb, d, Acad. Muenchen, 1879,
7
Alcoholic solution has strong acid reaction (Sitzb. d. ,\cad. Muenchen, 1870,
Alcoholic solution has acid reaction (Sitzh (l, Acad. Muerichen, 1879, p. 19).
I'orms yellow solution with ether (Journ. Dr. Chelm. T. (5, y: ($9 ).
Alcoholic solution has fa. Int acid reaction (Sitzb. d. Acad. Muenchen, 1879,
Arch. d. Pharm. 56, p. 253.
1 0
1 1
12
13
1 1.
Journ. pr. Chem. T 6, p. 78.
Journ. Dr. Chem. 9, p. 217.
Turned blue by ammonia (Compt. rend. 39, p. 196).
Contains two pigments (Compt. rend. , 50, p. 1182 " .
Yellow prec. with lead acetate (Chem. Centralbl. 3, p. 570).
Contains iron (Journ. pr. Chem. 16, p. 8 ' )
Contains glucoside of kamp herol (Journ. Chem. Soc. 81, p. 58.5).
Turnel green by and monia (Sitzb, d. A cutſ. Mut'nchen, 187 (), I, p. 17).
lſ as very faint, incid reaction (Sitzb, d. A (‘a (l. Muenclien, 1879, p. 19).
55
Color of Color of Col () l' () f
Observer. flower. , alc. Sol. residue.
ROSACEME.
Crataegus oxycantha 1.7 ........Perkin white
& & & 4 18;.......Wittstein white
Potentilla formosa. 19............Elsner red colorless red
otentilla reptans28........ .....Wogel yellow
Pyrus communis 18............... ..Wittstein
*Rösa odorata................ ........Brandel dark red colorless purple
*Hybrid Tea rose.................. .Brandel pink yellow brown
*Bourbon rose ‘Hermosa’....... Brandel pink colorless red
Rosa cinnamomea, 99............. Elsner red colorless red
Rosh centifolia. *[................... Hunefeld
( & { % *................... Vogel white
( & & 4 *................... Vogel red
$ 6 & 8 *................... Wogel yellow
Rosa gallica”....................... Elsner red colorless red
. . . “ ”....................... Hunefeld
( & “ ”....................... Senier red colorless
Spirea ulmaria 28................... Vogel white yellow
Spirea ulmaria *............... .... Loewig yellow yellow
{ { “ ”................. ..Buchner
Spirea filipendula 27............ .. Filhol white
Spirem opulifolia, L.28........... Ludwig
RUBIACE.E.
Gallium mollugo 99................ Filhol white
Gallium Verum 80........... ........Vogel yellow
RUTACEAE.
Citrus decumama 81................ Hoffman
Murraya exotica. 8°................ Hoffman
SAPINDACEAE.
Aesculus hippocastanum 88...Rochleder yellow yellow
{ % { {
84 ...Stein yellow yellow
16 Contains glucosides of isorhamme tin, quercetin and a third coloring matter
(Journ. Chem. Soc. 73, p. 267).
17
18
Contains quercetin as glucoside (Chem. News, 74, p. 278).
Contains propylamine (Ann. d. Chem. 91, p. 121).
19 Solution gives yellow prec. with lead acetate and yello wish - red prec. with
zinc chloride (Chem. Centralbl. 8, p. 572).
20 Same as 19.
21
22
23
24.
25
26
88, p
27
28
29
30
$1.
$2
S$
$4
Contains iron (Journ. Dr. Chem. 16, p. 84).
Contains quercetin also a red crystalline pigment (Ph. Journ. 36, p. 650).
Solution has acid reaction (Sitzb. d. Acad. Mue chen, 1879, p. 19).
Solution llas strong acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
Contains a crystalline substance called spiriin (J. pr. Chem. 19, p. 236).
Bº c intain salicin and flowers contain salicy lic aldehyde (Buchner's Ann.
Compt. rend 39, p. 194.
Bot. Centralbl. 21, p. 44.
Compt, rend. 89, p. 195.
Alcoholic sºlution has acid reaction (Sitzb. d. Acad. Muenchen, 1879, p. 19).
Contains glucoside maringin (Ber. 9, p. 690).
Contains glucoside murrayin (Ber. S., p. 690).
Buds are colorless, contain_quercetin glucoside (Chem. Centralbl. 30, p. 166).
Contains para-carthamin (Journ. pr. Chem. 89, p. 495).
56,
Color of Color of Color of
- Observer, flower, alc. Sol. 1'egldue,
SAPINDACE.E.
Aesculus hippocal Stanum 85...Hlasiwetz "..
Aesculus pavia, 84............ .......Stein red red
Acer pseudo-platanus 80........Stein
SAXIFRAGACEAE.
Hortensia speciosa 87............Schuebler -
Hydrangea quercifolia 88....... Marquart yellow
Philadelphus coronaria 89 ..... Filhol White
SCITAMIN E.E. - - -
*Canna (Golden Beauty)....... , Brandel yellow brown brown
* “ (Yellow Seedling)....... Brandel yellow yellow
* “ ( Pres. Cleveland)....... Brandel dark red brown bl’OWn'
* “ (G. O. Quintus).......... Brandel yellow yellow yellow
* “ (The Rival)................ Brandel yellow slightly yellow yellow
('anna limbata +"...................Marquart - -
Cannel indic: "...................... Elsner violet partly decolor. violet
SCRO PHULA RIACE.E.
*Antirrhinum majus............... Brandel red brown dark red
X. * { " ............... Brandel purple colorless brown
º: { { “ ............... Brandel yellow brown brown
X- { { “ ............... Brandel yellow yellow yellow
.1 mtirrhinum majus **............ Vogel reſl -
{ { “ -k3............ Schnetzler red
(ºnleedlºrin rugos 4+............... Vogel yellow -
Digitalis purpurea 45 ............. Elsner red partly decolor. red
{ { { { *"............. Vogel red t º
( ( ( { *............. Vogel white,
{ { ( (. *"............ .Vogel red
Linaria vulgaris 48...... ..........Riegel yellow
Linaria cymbalaria 49........... Vogel violet
Pentstemon diffusum 50.........Marquart, white
Veronical Spicate 51................ Hunefeld g
85 Contains quercetin (Ann. l (;hem. 1 12, p. 96). -
36 Contains ruti which yields quercetin (Journ: pr, Chem. 85, p. 351.)
87 Flower is ordinarily red but can be changed to blue by introducing carbon,
iron Ol' aluminum into the soil (Journ. pr. Chem. 1, p. 46). º
38 Flowers change to red upon fading (Arch. d. Pharm. 56, p. 262).
39 Turned yellow by ammonia (Compt. rend. 39, p. 194).
40 Contains red and yellow pigment (Arch. d. Pharm. 56, p. 257).
41 Aqueous solution gives a blue-green precipitate with lead acetate (Chem.
Centralbl. 3, p. 570). .
42 Turned blue by ammonia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
48 IForms colorless solution with borax solution (Jahresb. u. d. Fortschr. d.
(!hem. 1877, p. 925). - -
44 Not changed by ammonia (Sitz.b., d. Acad. Muenchen, 1870, I, p. 17).
45 Solution gives yellow pree, with lead acetate (Chem. Centralbl. 3, p. 57 ()).
46 Contains iron (Journ. pr. Chem. 16, p. 84). -
1. Alcoholic stylution has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879,
p. 19).
4S Used as dyestuff (Chenn. Centralbl. 14, p. 454).
49 Solution has acid reactio 1 (Sitzb. d._Acad Muenchen, 1879, p. 10).
B0 Becomes red upon fading (Arch. d. Pharm. 56, p. 263).
51 Journ, pr. Chem. 9, p. 217). * -
57
Color of Color of Color of
Observer. flow Gr'. alc. Bol. residue.
SCROPHULARIACE/E.
Veronica triphyllos?............Wogel blue
Veronica chamaedrys 52........Vogel blue
Veronica agrestis 52....... tº gº tº £ tº e º & Vogel blue
Verbascum migrum 49............Vogel yellow
Verbascum thapsus 58........... Hunefeld
SOLANCEAAE.
Fabiana, indica. 54........ tº $ tº g g g g tº ...Filhol yellow
Lycium barbarum 55 ..... tº ſº e s tº gº tº e Vogel red
Nicotiana Virginiana 50.........Vogel red
Petuna hybrida, 50......... ........ Vogel violet,
Physalis alkekenki 57............. Vogel red
Solanum dulcamara is.......... Vogel violet
TERNSTROEMIACEAE.
Camelia Species 59................ ... Filhol red
Camelia japonica. 90....... ........ Hunefeld
THYMELAEACEAE.
Daphne mezereum 91....... .......Rochleder rose
UMBELLIFERME.
Coriandrum sativum 62 ......... Vogel white
VERBENACE/E.
*Lantana delicatissimum ....... I3randel lilac colorless pink
* Lantana Camara........... ... ..... Brandel yellow yellow yellow
* Verbena tenera maonetti...... Brandel blue colorless blue
* Verbena (red)...... .......... .......Brandel red slightly pink purple-red
Verbena hybrida. 63............ ....Vogel red
( & ‘‘ 64........ * & 9 tº e º ſº º Vogel blue
Verbena officinalis 08 .............Wogel red
WIOLACEAE.
|Viola (Violets)............. tº e º e º ſº º e ºs Brandel blue colorless blue
Viola tricolor.05.............. .......Marquart yellow
52 Solution has faint acid reaction (Sitzb. d.
58 Contains iron (Journ. Dr. Chem. 16, p. 84)
54 Compt. rend. 50, p. 1182.
Acad. Muenchen, 1879, p. 19).
º, Aqueous solution has strong acid reaction (Sitzb. d. Acad. Muenchen, 1879,
p 56 Turned green by ammonia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
57. Not changed by ammonia (Sitzb. d. Acad. Muenchen, 1870, I, p. 17).
58 Alcoholic solution has faint acid reaction (Sitzb. d. Acad. Muenchen, 1879,
p 59 Turned blue by acids (Compt. rend. 50, p. 545).
60 Journ. pr. Chem. 16, p. 69.
ºgontain. glucoside daphn ne which yields daphne time (Journ. pr. Chem. 90,
I).
42).
62 Turned yellow by ammonia (Sitzb. d. Acad. Muenchen, 1870. I, p. 17)
68 Alcoholic solution has strong acid reaction (Sitzb. (l. Acad. Muenchen, 1879,
64"Alcoholic solution has neutral reaction (Sitzb. d. Acad. Muenchen, 1879,
§§ Arch. d. Pharm. 56, p. 257.
58
\
(Xol Ol' Of Color of Color of
()bser yer. ſlo Wer. alc. Sol. res! (lue.
WIOLACEE.
Viola tricolor 66............. e ſº tº e º e º e Elsner red colorless red
( & “ "..................... Hunefeld yellow
4 & “ ”..................... Vogel blue
Viola tricolor........................ Brandel purple pink purple
Viola tricolor maxima, 69...... Vogel blue
Wiola maxima 79,................... Vogel yellow
Viola cornuta 08 ........... tº tº dº e º ºs e º & Vogel blue
Viola odorata 71.................... Macaire blue
( & & 4 *.................... Hunefeld blue
Theories of Plant Pigmentation. The study of the pig-
ments in the colored organs of plants, very early attracted the
attention of chemists as well as of botanists. Wirey 1 in 1811
attempted to show that the colors in different plants were dependent
on their medicinal properties.
On account of the great predominance of green in the vegetable
kingdom, it was but natural that the early investigators should
consider the other plant pigments as related to the green pigment,
first called chlorophyll by Pelletier.” This point of view was empha-
sized by the recognized importance of the chlorophyll to the life of
every plant, and by the study of the deportment of chlorophy}l to-
wards light, heat and chemical reagents. That clilorophyll is a
a mixture of substances of different colors was first shown by
Mueller 8 who noticed that upon evaporating an alcoholic solution
of chlorophyll, a series of colored rings were formed. The outer ring
was yellow, then followed a bluish ring and finally the green.
Mueller therefore argued the existence of three pigments in chloro-
phyll. According to Hartsen 4, 1872, the yellow pigment can be ob-
tained in a crystalline form. This substance he called chrysophyll.
By shaking an alcoholic solution of chlorophyll with benzene, Kraus 5
obtained a golden-yellow substance which he called xanthophyll and
66 Solution gives dark green prec. with lead acetate and violet with zinc
clıloride (Cnem Centralbl. 3, p. 572).
º yellow solution with oil of turpentine (Journ. Dr. Chem. 16, p. 68;
9, p. 217).
1. Alcoholic solution has faint acid reaction (Sitzb. d. Acad. Muenchen, 1879,
I). *g
º Alcoholic solution has neutral reaction (Sitzb, d. Acad. Muenchen, 1879,
p. 1
70 Not changed by ammonia, (Sitzb. d. Acad. Muenchen, 187 (), I, p. 17).
71 Turned green with alkalies and red with acids (Ann. de Chim. [2] 38, p 41 5).
72 Journ. pr. Chem. 9, p. 217.
1 Journ. de Pharm., 3, p. 529.
2 Journ. de Pharm., 3. p. 486.
8 Jahrb. f. wiss Bot. 7, p. 200.
4 Chem. Centralbl., 1872, p. 525; 1875, p. 613.
5 Bot. Ztg., 30, pp. 109, 127, 538, 588.
59
a blue-green substance which he called cyanophyll. The mixture of
these two pigments again produced the green chlorophyll.
By shaking chlorophyll with a mixture of ether and hydrochloric
acid, Fremy 9, 1860, obtained a yellow ethereal layer and a blue
acid layer. The chlorophyll, therefore, according to his ideas con-
sisted of two pigments— a yellow, called phylloxanthine and a blue,
called phyllocyanine — in variable proportions. The phyllocyanine
was regarded as being present in the form of a potassium salt, be-
cause of the large quantity of potassium chloride which separated
from the hydrochloric acid solution.
Most authors agreed that the blue pigment of chlorophyll readily
underwent changes, and it was to this pigment that they most often
looked for the source of other pigments. The yellow color of fall
leaves is explained by Fremy 7 by assuming the complete decomposi-
tion of the blue phyllocyanine, the leaf being then colored only by
the yellow pigment. The presence of this pigment in variable quan-
tities would produce different shades of yellow. Besides undergoing
complete decomposition during the life process of the plant, the blue
pigment was thought to be able to undergo such changes as would
result in the formation of a new pigment. Thus according to Kraus,8
1872, the brown coloration in leaves is caused by a peculiar modifi-
cation of this blue constituent of chlorophyll; and, according to
Haberlandt,9 1876, this modification can be brought about only by
the frost. Both authors agree that a red pigment called anthocyan
is also produced from the blue constituent of chlorophyll. By
treating chlorophyll with dilute potassium hydroxide, Hardsen 10
obtained a purple pigment which he called purpurophyll, and which
he mentions as a possible pigment of blue flowers. Hoppe-Seyler 11
in 1879 isolated two crystalline substances from the chlorophyll of
grass, a red substance, identical with Bougarel's erythrophyll which
was found in the leaves of sycamore and peach 12; and a yellow
substance to which he gave the name chlorophyllan.
In the same way as chlorophyll could produce such a variety of
pigments closely related to and still associated with chlorophyll itself
6 Compt. rend., 50, p. 405; 68, p. 18S.
7 Compt. rend., 50, p. 405.
8 Bot. Ztg., 30, pp. 109, 127, 558, 568.
9 Chem. Centrall, l., 47, p. 357.
10 POgg. Ann., 146, p. 158,
11 Ber. 12, p. 1555.
12 Bull. Soc. Chim., 27, p. 442.
(3()
in leaves, so by more radical and complete changes the pigments of
the flowers were produced.
This argument seemed the more reasonable because of the fact
that flower buds are green.
According to Marquart, 18 1836, the color of all flowers is due
to one of two pigments, derived from chlorophyll, or sometimes to
both pigments. One of these two fundamental pigments is yellow,
the other blue. The yellow pigment was called anthoxanthin and is
the substance which gives its color to all yellow flowers. The blue
pigment is called anthocyan and is the pigment found in all blue
and violet flowers. The pigment in red flowers is the blue anthocyan
colored red by acids formed during the life process of the plant. The
author claims that the aqueous solutions of all red flower pigments
are acid in reaction. Upon very careful neutralization, the blue
anthocyan can be obtained. On the other hand, solutions of blue
anthocyan become red upon the addition of acids. White flowers
owe their color to a substance called “Blumenharz” which is con-
sidered to be an intermediate product in the changing of chlorophyll
to anthocyan. In the buds all flowers are green. If the chlorophyll
takes up water or the elements thereof, anthoxanthin is formed and
the flower becomes yellow. The green buds of white flowers, become
white by the abstraction of water from chlorophyll and if this ab-
straction of water be continued the blue anthocyan is formed.
According to the author, white flowers can be changed to red by
treating them with a dehydrating agent like sulphuric acid. Whether
the flower becomes blue or red is determined by the following con-
ditions. If only carbonic acid be present in the bud, this is breathed
out as the bud opens and the flower becomes blue. It is because
they are not able to breath out the carbon dioxide that the buds
of even blue flowers are red. If, however, a fixed acid be present in
the bud, the flower becomes red. All intermediate colors are due to
various admixtures of anthoxanthin, anthocyan and chlorophyll.
Schuebler14 in 1827, attempted to show the relation of the
various plant pigments other than green to each other and to
chlorophyll. He devided all pigments into two groups, the yellow-
red group and the blue-red group. Between these two, was the
chlorophyll. The yellow-red group contains the pigments produced
13 Arch. d. Pharm., 56, p. 244.
14 Arch. d. Pharm., 20, p. 262.
61
by various degrees of oxidation of the chlorophyll, while the pig-
ments of the blue-red group represented various stages of deoxidation
of chlorophyll. It is not clear from his article upon what he based
this assumption nor does he try to explain how this oxidation and
deoxidation is brought about in the plant. His arrangement of
colors is shown in the following table:
Red
Orange-red
Orange
Orange-yellow
Yellow
Yellowish /
Chlorophyll
Blue-green
Blue
Blue-violet S Deoxidation
Widlet-red
Red
Chlorophyll, therefore, is the basal substance of all pigments,
changing on the one hand to oxidized pigments and on the other
hand to the deoxidized pigments. This was in harmony with the
fact that both yellow and blue flower pigments could be changed
into red. That the two reds thus obtained were different substances
is shown by the fact that the red obtained from blue flowers, could
be changed back to blue by the addition of dilute alkali, while the
red pigment resulting from yellow flowers could not be changed to
blue by means of alkali. The flowers colored red naturally could
also be devided into two classes according to their behavior toward
caustic alkali.
In opposition to this, Elsner, 15 1832, as well as others held that
all red flowers contained the same red pigment, because of the
similarity of their behavior toward chemical reagents and that the
red coloring matter in leaves and fruits is also identical with that
from red flowers.
However, the majority of persons who worked on plant pigments,
did not venture to explain the relation of these pigments to chloro-
phyll but were satisfied with the general statement that all flower
pigments are due to slight changes produced in the chlorophyll by
acids or alkalies. 19
Oxidation
15 Chem. Centralbl. 3, p. 567.
16 Bot. Centralbl., 5, p. 103.
($2
In some instances a special change was attributed to the chloro-
phyll which was characteristic of an individual plant. Thus Witt-
stein 17 examined the red pigment in the leaves of Vitis hederacea.
This pigment, he called cissotannic acid, C20H12016, and regarded
it as a decomposition product of chlorophyll. This cissotannic acid
is supposed to exist in the plant as the ammonium salt, the
ammonia coming from the nitrogen of the chlorophyll.
In order to explain the formation of the green chlorophyll as
well as other pigments in a plant, Macair-Princep, 18 1828, assumed
the presence of a fundamental substance underlying all plant pig-
ments which he called “chromul.” This is assumed to be an almost
colorless substance which by the action of alkalies is changed to
green chlorophyll. This in turn is changed to yellow and then to
red by the action of oxidizing agents or acids. Thus a green leaf
in contact with acids becomes yellow, the green being restored by
the addition of alkali. A yellow autumn leaf when placed in a
solution of a caustic alkali again becomes green. The fall coloration
of leaves is, therefore, regarded as being due to the absorption of
larger quantities of oxygen. The “chromul” is also the funda-
nmetal pigment substance in flowers, for red flowers when treated
with alkali become green. Blue flowers obtain their color by the
union of the red “chromul” with plant alkalies or all;aloids. For
this reason some red flowers become blue when brought in contact
with quinine.
According to Berzelius 19, 1837, the assumption of a fundamental
substance, like Macaire-Princep’s “eliromul”, is entirely unfounded.
He claims that it is impossible to change a green leaf to yellow or
red by means of acids and back again to green by means of alkalies.
That some red pigments become green when treated with alkalies, is
not due to the formation of leafgreen but to the formation of a
compound of the red pigment with the alkali.
In 1837, Hoppe 90 regarded the “chromul” of Macaire-Princep as
the fundamental substance which produced chlorophyll or green
plant pigments only. In other colored parts of a plant he assumed
the presence of an entirely different basal substance or rather a
mixture which he called chromogen. This was a colorless substance
17 Jahresb. u. (l. Fortschr. d. Chem. , 6, p. 564.
18 Ann. d. Chim. (2), 38, p. 41 5.
19 Pogg. Ann., 42, p. 422.
20 Journ. f. prakt. Chem., 10, p. 269.
63
consisting of two compounds, viz. erythrogen and xanthogen. The
former of these, by the action of acids, forms the red plant pigments;
and the latter, by the action of alkalies, forms the yellow pigments.
White flowers contain unchanged colorless xanthogen because white
flowers become yellow by the action of alkalies. Yellow flowers con-
tain only xanthogen while blue and red flowers contain both
erythrogen and xanthogen. Slight variations in color are due to
compounds of erythrogen and xanthogen with other vegetable
principles.
Instead of assuming the presence of one basal substance Wirey 21
in 1838 also referred plant coloring matters to two basal substances,
a yellow pigment and a blue pigment. Chlorophyll was a union of
these two pigments. This agreed with the accepted notion that
chlorophyll consisted of a blue and a yellow pigment. Red flowers
contained the blue basal pigment which was turned red due to the
development of some acid principle in the plant, and not infrequently
yellow flowers turn red. Upon fading the color of flowers always
goes back to their primitive basal color. Thus the red rose turns
yellow, the red hortensia upon drying turns blue. White flowers
upon fading turn either yellow or blue. The terms xanthine and
cyanine first applied by Decandolle 22 to plant pigments were used
by Wirey to designate his yellow and blue basal pigments respectively.
Wirey objected to regarding the yellow pigments as oxidized deriva-
tives of chlorophyll and the blue pigments as deoxidized pigments,
because many blue flowers are white or red in the bud, becoming
blue as the petals come in contact with the air. Therefore, blue
pigments can not be the result of deoxidation. Virey attributed the
differences in color of flowers, to differences in the composition of
the plant juices or to differences in the composition of the soil, in
which the plants grow. The color of a flower very largely depends
also upon whether the plant blooms in early spring, in summer or
in falſ. Although flowers of every color bloom at any one time,
there are more white and blue flowers in the spring time, more red
in the summer, and yellow predominates in the fall.
The color of flowers, as affected by the composition of the soil,
referred to by Wirey, had already been given as an explanation for
changes in color by Schuebler and Lachenmeyer 28 in 1834. They
21 Journ. de Pharm., 30, p. 661.
22 Journ. f, prakt. Chelm., 1, p. 46.
64
found that the presence of considerable quantities of carbon and
ferrous oxide in the soil changed the red hortensia to blue. The
authors explain this by saying that soils containing a considerable
Quantity of these easily oxidized substances are in a deoxidized con-
dition. In the absence of these substances, the oxygen would be
used to oxidize stronger acid-forming substances and then the flowers
would bloom red. On this same basis of increasing or decreasing
deoxidation, as the plant and fruit developes, the color of the ripened
fruit is explained. Unripe green fruits turn yellow, then red and
finally blue. Unripe fruits containing a large quantity of acids upon
ripening turn only to red. If the quantity of acid diminishes greatly
upon ripening the fruit assumes a bluish color as in the case of
grapes. *
From about 1855 on, the attempt at explaining plant pigment-
ation on the basis of the relation of pigments to chlorophyll, was
gradually abandoned. However, the idea of basal substances under-
lying the different plant pigments, or groups of pigments, in all
flowers without being related to chlorophyll, was still held for some
time. But gradually the discovery of new plant constituents and
their derivatives led to attempts to explain the color of limited
groups of flowers.
Previous to this time, Huenefeld 24 in 1839 had already made an
attempt to get away from the idea of plant pigments being modified
chlorophyll. From the behavior of a large number of flowers to-
wards different solvents, the conclusion was drawn that plant pig-
ments have certain radicals, as a basis, which, however, are different
in different plants. “Die Pflanzenfarben gehören mit zu den am mei-
sten speciell metamorphosirten Stoffen.” They are specific substances
like the volatile oils, even if their manifoldness can be brought about
by very simple means. The color changes produced by the fading
or dying of the flower are due to the fact that with the retarded
vegetation, the consumption of carbon ceases and the absorption of
atmospheric oxygen increases, thereby destroying the pigments.
Among all the plant physiologists who had studied plant
pigments up to this time, Preisser 25 was the only one to re-
gard plant pigmentation from a standpoint entirely different from
that of his co-workers. He attributed the color in any one plant to
24 Journ. f. prakt. Chem., 16, p. 65.
25 Journ. de Pharm. et de Chim. (3) 38, pp. 191, 249.
65
the presence of a chemically definite plant constituent, which was
peculiar to that plant or allied plants. ' To his mind, therefore, the
study of plant pigments meant 1) the study of such colored plant
constituents, like quercetin, luteoline, indigo, morrin, etc., as were
known at that time; 2) a study of the chemical changes which
commonly go on in a plant; and 3) a study of the changes brought
about in the various colored plant constituents when subjected to
similar chemical reactions. He makes no mention whatever of mix-
tures like cyanine, xanthine, etc., commonly studied by plant
chemists. He speaks of chlorophyll only to say that it must be
more thoroughly studied. In the roots of all plants there is a
constant process of reduction going on forming derivatives of the
plant pigments, which are not colored. In the leaves and flowers,
however, a process of oxidation is going on so that all the modifi-
cations of color noticed in the same plant are derived from the same
plant constituent in different states of oxidation. Thus the brown
color of Rhus cotinus is due to the yellow fustin, which has been
changed by the action of ammonia, and the oxygen of the air. It is
for this reason that the color of a plant can be destroyed with
reducing agents and restored again with oxidizing agents. Preisser
also thought that these colored plant constituents did not exist in
the plant as such but as their metallic derivatives, especially sodium,
potassium and ammonium.
Fremy and Cloez 20 in 1854 were the first to object to regarding
pigments as derived from chlorophyll on the ground that neither the
pigments nor the chlorophyll had been obtained in a pure condition
and, therefore, no such conclusions were warranted. The main object
should be to determine what the pigments themselves are. According
to these authors there are three pigments found in plants. Cyanine
is the pigment in blue flowers. This is a blue amorphous substance
which dissolves in alcohol to a colorless solution and upon evapora-
tion leaves a blue residue. The red or rose colored flowers Owe
their color likewise to cyanine which is changed in color by different
degrees of acidity of the plant juice. The yellow pigments of flowers
have no relation to and can not be derived from the red or blue pig-
ments as claimed by others. There are two entirely different yellow
pigments found in flowers. These two pigments are not related to
each other and are called xanthine and xantheine. The fact that
26 Journ de Pharm. (3) 25, p. 249.
66
some yellow flowers turn red is explained by assuming that the
flowers also contain some cyanine and as the yellow pigment is
destroyed the cyanine shows up its color.
Martens, 27 who adopted the theory of Fremy and Cloez in 1855,
traced the origin of xanthein back to a light yellow plant juice
which the plant formed in the parenchyma cells. By the action of
light and alkalies, it takes up oxygen becoming more and more
yellow. This “Extractivstoff” by further change and subsequent
uniting with fatty substances produced the different yellow pigments
of leaves and flowers. These yellow pigments by the continued
action of light and oxygen are changed to red. Cyanine is the pig-
ment in blue flowers and is generally accompanied by traces of yel-
low pigments.
Phipson, 28 1858, extracted a substance from the wood of Rham-
nus trangula which he called rhamnoxanthine. This substance had
similar properties to Xanthophyl, the yellow pigment in fall leaves,
but is probably not identical with it. Yellow leaves when dipped
into sulphuric acid become emerald green, continued action turning
them yellow or brown. Rhamnoxanthine acts in the same way and
therefore may be the pigment found in some leaves.
In 1859, Rochleder 29 isolated the glucoside quercitrin and its
product of hydrolysis, quercetin from the flowers of a number of
plants. The flower buds did not contain these substances and he
assumed, therefore, that they were formed in the flowers. The author
attributed the yellow color of the specific flowers examined to the
presence of quercetin.
In the same year, Hlasiwetz 80, as a continuation of Rochleder's
work, made a detailed chemical study of quercetin. From the results
obtained he devised a general theory of plant pigmentation. Upon
heating quercetin with caustic potash, he obtained phloroglucin and
a substance which was called quercetinic acid. Accordingly, yellow
flowers owe their color to quercetin. The fact that some yellow
flowers turn red is explained by assuming that quercetinic acid is
formed which is colored red in the presence of alkali and oxygen.
Quercitrin, the glucoside of quercetin, gives a brown color in the
presence of alkali and oxygen. Quercetinic acid in the presence of
; ſº, ſº them, 8, p. 657. º,
29 Journ f. Drakt. Chem., 77, p. 34
80 Journ. f. prakt. Chenn., 78, p. 257.
67
iron oxide gives a blue coloration and a mixture of red and blue
would explain the presence of violet. The author regrets that the
amount of pigment in the flowers is so small that these compounds
could not be isolated from the flowers directly.
Stein 81 isolated from the flowers of Sophora japonica, Leucoiu on
Vernum, Acer pseudo-platanus, and Cornus mascula, a substance
which was identical with rubinic acid or rutin, first isolated from
the herb of Ruta graveolens by Weiss.8° Because of its occurrence
in so many other plants besides the one from which it obtained its
name, Stein called it ‘Pflanzengelb’, ‘Phytomelin' or simply ‘melin'
(from Greek pºtvos, Quittengelb).
By some melin was supposed to be identical with quercitrin.
Upon careful study, however, Stein found the two substances to be
different although upon hydrolysis both yielded quercetin. The quer-
cetin from melin, Stein called meletin. Upon reduction with sodium
amalgam, melin as well as meletin yields a red substance called para-
carthamin. This compound was made the basis of his theory of plant
pigmentation. Many red flowers upon treatment with alkali become
green thus behaving as does paracarthamine in the test tube. The
flowers in the bud contain meletin and are therefore yellow, but
become red as the meletin is changed to paracarthamine. The pig-
ments of blue flowers are compounds of the red pigment paracar-
thamine with weak bases. Thus the pigment in the blue flowers of
Centaurea cyanus, is supposed to be the calcium derivative of para-
carthamine.
According to Wigand 88, 1862, tannin plays a very important
role in the chemical processes which take place during the life of a
plant. For example, the unripe fruits are rich in tannin content
which decreases upon the ripening of the fruit at the same time that
the sugar content increases. The tannin, therefore, is supposed to
be changed directly into sugar. In the same way all red and blue
plant pigments with the exception of indigo and a few others are
supposed to be derived from tannin by very slight changes, as is
shown by the fact that the pigments have almost the same chemi-
cal properties as tannin and can very readily be changed back to it.
Many of the natural red dyestuffs are not found in the plant as
ºsº
81 Journ. f. prakt. Chem., 85, p. 351.
32 Pharm. Centralbl., 1842, p. 903.
88 Bot. Ztg, 20, p. 12l.
68
such, but as a colorless substance which is changed by the action of
air or alkalies to the red dyestuff. This colorless substance the
author calls, cyanogen and thinks it closely related to tannin be-
cause of its behavior towards chemical reagents. Furthermore this
cyanogen is only found in tannin-containing plants and only in
those cells which originally contained tannin.
The red leaf pigment he regards as in no way related to chloro-
phyll; for either the two pigments are found in different cells or, if
they are found in the same cell, the red pigment is dissolved in the
cell sap while the chlorophyll is found in the form of granules. This
red leaf pigment originates again from a colorless substance which
is supposed to be identical with tannin for the following reasons:
1. The red coloration of leaves is found only in such plants as
contain tannin.
2. The red pigment is found only in those cells which have pre-
viously contained tannin.
3. The red cell-sap gives the same green or blue color when
treated with ferric salts as does tannin.
The red and blue colors of flowers according to his interpretation
are directly due to the presence of anthocyan which is an oxidation
product of tannin. This assumption depended merely upon the fact
that blue and red flowers are decolorized by reducing agents like
sulphur dioxide and that white flowers become red when treated
with acids.
Sorby 84 in 1871, divided all plant pigments into five groups.
I. Chlorophyll Group. Chlorophyll is not a single substance.
Different plants contain different chlorophylls. The leaves of most
plants are colored green by a mixture of two or more kinds of
chlorophyll. Some kinds of chlorophyll are turned blue with hydro-
chloric acid; others are not. -
II. Xanthophyll Group. To this group belong the yellow pig-
ments of leaves and flowers insoluble in water but soluble in alcohol
and carbon disulphide.
III. Erythrophyll Group. This contains the red pigments. These
pigments are of various degrees of red, their color is intensified by
acids and turned to blue or green by alkalies. These red pigments
form colorless solutions with alcohol and leave a red residue upon
evaporation.
84 Chem. News, 28, pp. 137, 148.
69
IV. Chrysophyll Group. These are golden yellow pigments
soluble in water and insoluble in alcohol and carbon disulphide.
W. Phaiophyll Group. To this group belong the brown pig-
ments.
In as much as in the explanation of the fall coloring of leaves,
the same sort of reasoning was applied as was often times used for
flower pigmentation, Sorby's explanation of the fall coloring of
leaves will not seem out of place here.
The endless variety of autumnal tints of leaves he regards as
commonly due to varying mixtures of pigments, belonging to two
or more of the above groups. Unfaded green leaves are colored
mainly by chlorophyll, but the tints are modified by colors of the
xanthophyll and chrysophyll group. This explains why we find
varying shades of green in different leaves. On shaking an alcoholic
extract of a green leaf with carbon disulphide, the chlorophyll will
be removed leaving the xanthophyll in the alcohol. This chlorophyll
has a much brighter green color, than the leaf had. The presence
of pigments of the erythrophyll group produces brownish tints. If
erythrophyll preponderates over the chlorophyll we have red
or even- purple-green as in the case of copper-colored and purple
beech leaves. In autumn, the chlorophyll decomposes leaving the
xanthophyll or erythrophyll. Thus the yellow color of faded leaves
is due to the xanthophyll and the red color to the erythrophyll
which previously existed in the leaf, the alteration in color consist-
ing merely in the disappearance of cisloropllyll.
Rosoll 85, in 1884, isolated a yellow coloring matter from the
flowers of Helichrysum bracteatum and Helichrysum arenarium which
he called helichrisin. This is a yellow amorphous powder which gives
red derivatives with the heavy metals and forms blue solutions with
both acids and alkalies. The author believes it to be a quinone
like compound, because it is easily decolorized by reducing agents.
The color of the flowers is supposed to be due to helichrysin or its
derivatives. f
In as much as the phenomenon of color is a physical manifesta-
tion, the physical study of the subject of plant pigmentation readily
manifested itself. Much of the work of determining the pigments in
a flower was done, both by chemist and botanist, by determining
35 Monatsh. f. Chem., 5, p. 94.
70
the absorption band in the spectrum. Thus Hansen 86 in 1884 says
that all yellow flowers owe their color to the same yellow pigment
which on account of its similarity to animal lipochromes, he calls
flower-lipochrome. All red flowers owe their color to the same red
pigment. This is determined by the fact that most red flowers give
the same absorption bands in the spectrum. The blue and violet
pigments are derivatives of the red pigments. By the action of acids,
the blue pigment turns red. The spectrum of the blue pigment,
turned red by acids, is the same as the spectrum of the pigment of
flowers which bloom red.
By treating a mixture of phenol and ammonia with hydrogen
peroxide, Wurster 87 obtained a blue solution which gradually became
green and then yellow and finally with an excess of hydrogen
peroxide the solution became colorless. Upon the addition of acids,
the blue solution turned red, from which solution Wurster isolated
phenolduinoneimide, first prepared by Hirsch.88 Wurster noticed the
similarity of the behavior of this compound to that of red and
blue flowers and suggests it as a possible explanation of plant pig-
mentation, although he had not isolated a quinoneimide from a
single flower.
Hydrogen peroxide is formed in a greater or lesser quantity
during the life process of the protoplasm. Hydrogen peroxide can
be easily identified in the juices of many plants, also in flowers and
seeds. Therefore, in the presence of ammonia and a phenol, which
occur so widely distributed in the vegetable kingdom, a phenol-
duinoneimide could be formed. Thymol and other phenols found in
plants readily form the corresponding quinoneimide. Resorcin, when
heated with ammonia and hydrogen peroxide gives a blue solution.
Resorcin when melted with quinone gives upon the addition of
ammonia, a deep green solution. Upon shaking this solution with
air, it gradually turns yellow, then red and finally brown. Wurster
compares this color changes to the color changes which some leaves
undergo as for example the Berberis species. Nothing is said, how-
ever, about the occurence or the source of the quinone necessary for
these changes. º
In 1893, Nienhaus attempted to explain the formation of violet
pigments, by assuming the formation of carbaminic acid from the
ammonia and carbon dioxide of the air. He says the changing of
red pigments to violet is not an oxidation process as is sometimes
36 Bot. Centralbl., 20, p. 36.
87 Ber. 20, p. 2934.
88 Ber. 13, p. 1909.
71
thought. The red flowers of Papa ver rhoeas when dried in the air
always turn violet. By drying them in an atmosphere absolutely
free from ammonia, the flowers retain their red color.
According to Molisch 39 the Phaeophyceae, Diatomaceae and
some Orchideae contain a brown coloring matter which is closely
related to chlorophyll and is called phaeophyll. It is readily changed
to chlorophyll. It is for this reason that the brown algae rapidly
become green in hot air, hot water, alcohol, etc. This phaeophyll
plays the same function toward these brown p'ants, as the chloro-
phyll does to the green plants. *
The Phaeophyceae and Diatomaceae also contain leucocyan
which with acids give the blue or blue green phaeocyan.
From the examination of a large number of flowers by means
of the Leitz micro-spectroscope, Kraemer 49 draws the following
conclusions in regard to color in plants:
There are two classes of color substances:
(a) Organized color principles characterized by being an organic
part of the plastid body; insoluble in water or dilute alcohol;
soluble in xylol, etc. This class consists of three main pigments:
chlorophyl; chromophyl found especially in the flowers, certain
roots, and ripening fruits of higher plants; etiophyl found especially
in the leaf-bud of Spathyema foetida.
(b) Unorganized color principles, which are not a fundamental
or organic part of the plastids, and occur either in the vacuoles of
the cells of higher plants as well as fungi or in the vacuolules of the
plastids of the brown and red sea-weeds. They are soluble in water
and dilute alcohol and insoluble in xylol, etc. Unorganized color
substances are produced in large amount in early spring foliage,
foliage of alpine plants as well as autumnal foliage; the brown and
red marine algae; and the foliage of certain species of rose, beech
nasturtium, etc.
Willstätter 41 who undertook a careful study of the composition of
chlorophyll with special reference to the separation and characterisa-
tion of chlorophyll derivatives by treatment with acids and alkalies,
has isolated a great number of substances colored and colorless,
which, however, have not been shown to have any special bearing or
relation to flower pigments. It is, however, interesting to note, that
the term chlorophyll as commonly used is a mixture of substances,
the principle One of which is a complex magnesium derivative. Two
39 Bof. Ztg., 63, p. 131.
40 Proc. Am. Phil, Soc., 43, No. 177; Bull. Torrey Bot. Club, 33, p. 77.
41 Ann. 350, pp. 1, 48; 354, p. 205; 355, p. 1.
72
yellow pigments which accompany chlorophyll, are carrotene and
xanthophyll. The carrotene is probably identical with the carrotene
from carrots, and also with Bougarel's erythrophyll 49 and Schunck's
chrysophyll. *
While without special reference to plant pigments, it is interest-
ing to note a general explanation of the cause of color in organic
compounds by Hale, 48 From a study of a large number of com-
pounds, he draws the conclusion that isorropesis is the cause of color
in aromatic as well as the aliphatic series. By isorropesis is meant
the making and breaking of contact between atoms which give
marked activity to these atoms. This change of linking, therefore,
which must accompany the transformation of one modification of
the compound, into the other #
-º-º- —) —CH=C– cº-º-º-º: -—) cº-º-º-ch.
(— K––
OH () O O O
is the source of the oscillations producing absorption bands. If
these oscillations are synchronous with light waves of a high fre-
Quency, they give rise to absorption bands in the ultra violet or in-
visible end of the spectrum and the compound is colorless. If the
oscillations are of a less frequency, the absorption band appears in
the visible region of the spectrum and this absorption of colored
rays, results in the compound taking on the complementary color.
From this survey of the theories which have been advanced as
so many attempts to explain the various color phenomena in plants
it will readily be seen that nothing satisfactory has been accom-
plished.
With the exception of one or two cases, no definite compound
had been isolated. The theories are mostly based on flower extracts
which at best are complex mixtures and to which practically each
author gives different names. Even in those instances in which a
theory was based upon a definite chemical compound this, as a rule,
was not isolated from plants. The explanation of plant pigmenta-
tion consisted solely in a comparison of the 'color of flowers with
the colors produced by the action of different chemical reagents upon
this compound.
On the other hand, in those few instances in which a definite
plant constituent was made the basis of a theory, chemical changes
were assumed to take place which could not be definitely explained.
Nothing was known of the nature of the resulting product except
that it was colored.
42 See p. 59.
48 Pop. Sec. Monthly, 72, p. 116,
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Percolation
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Percolation
By
I. W. BRANDEL and EDWARD KREMERS
MILWAUKEE
Pharmaceutical Review Publishing Co.
1908
*…:28%
4-10-417
Historical Introduction. The verb “percolate” [from per,
through, and colate, to strain], was formerly applied to the process
of filtering or straining. It applies generally to the passing of a
liquid through fine interstices [e.g. “water percolates through porous
stone”], and has been used pharmaceutically since the middle of the
nineteenth century to designate extraction by displacement.
To extract [from ex, out, and trahere, to draw] means literally
to draw out or forth. The term extraction has been applied to the
process of distillation and even to chemical processes, as well as to
the method now commonly employed when the process of extraction
is referred to.
To displace [from Fr. déplacer: prefix dis place] means literally
to change the place of [Ger. deplaciren = Verdrängen]; Displacement
[Fr. déplacement, Ger. Deplacirung = Verdrängung] is the act of
displacing or fact of being displaced. As used pharmaceutically" and
chemically it implies the displacement of a more or less saturated
solution by one less Satur- .
ated.
In chemical technique e.g.
the removal of the mother
liquid from a precipitate is
displacement.
Pharmaceutically, how-
3/NºSQNºzzº
---------
;/T&
*
cº-ºr-
E-
E-
*-->
#-Tº-º-º-º-º:
ńſ
º#E:45
ever, the term and its more ######
ÉYºs:
common synonym percola- Hååå%
tion 2 are less used to desig- º
nate processes of purifica- Haº;
* * - - E ºšfis
tion but rather a certain E. *ašETE
process of extraction, espe-
cially of powdered crude
drugs. The present use of
this term is analogous to
that. of the older term - - -
lixiviation, 8 common in Fig. 1. Manufacture of Saltpetre. , 1557.4
º B. is a vat in which the salpetre earth
chemical technology. is lixiviated.
1 Boullay (1833) claims credit for having introduced the terms “method of dis-
placement” and “process of displacement” into pharmaceutical literature.
2 In the bibliography. Q. v. the term percolation appears to be flrst used by
Squibb.
8 Soubeiran (18:36) defines displacement as “lixiviation employed on vegetable
substances.” Faraday in his “Chemical Manipulations,” 3rd ed. 1842, p. 193, still
uses the term “liviviation” describing it as a convenient process for the extraction
(percolation) of vegetable substances.
4 Agricola, Dere metallica. German edition of 1557. Reproduced from Peters,
Aus pharmaceutischer Worzeit. Ból. II, p. 144.















2
The terms displacement and percolation, therefore, apply to a
process of extraction different from the older processes of maceration
and digestion as employed pharmaceutically.
Réal 1 is commonly given credit for having applied the process
Of lixiviation, using this term in its broader sense, to the extraction
of comminuted, dried vegetable products.
The earliest descriptions and illustrations appear in 1816.” The
&
Fig. 2. Original and Modified Réal Filter-Press.
1 Pierre François Réal, made count by Napoleon, was born 1757 in Chatou near
Paris. He was a manufacturer of liquors and toolk an active part in the French Revo-
lution. He continued his political activity under Napoleon and in 1814 he was made
Prefect of Police Having been banished in 1815, after the downfall of Napoleon,
he resumed his trade as distiller in Belgium. He returned to Paris in 1818, where
he died in 1834. *
2 The original account has not yet been traced by the writer.
Cadet gave an illustrated account of it in
1816, in the Journ. de Pharm., 2, p 165, e lited by him. This was immediately
translated by Buchner and published with comments and the reproduction
of the plates in his
1816, Repertorium der Pharm., 2, p. 356. Other accounts in German journals of
that time appeared by Doebereiner in
1816, Schweigger's Journal, 16, p. 339; also
1817, Gilbert’s Annalem, 60, p. 14.
1817, Geiger, Beschreibung der Réal’schen Auflösungspresse. Pamphlet, pp. 22.
Heidelberg, Mohr u. W.
Later descriptions may be found in the following pharmaceutical works :
1822, Buchner, Einleitung in die Pharmacie, p. 247. Illustrated : Plate II, fig. 50.
1830, Geiger, Handbuch der Pharmacie, 3rd ed., p. 140.

3
apparatus was designed primarily for the extraction of “coffee, tea,
cinchona bark, nut galls, hops, etc., or for the purpose of obtaining
strong alcoholic tinctures for the preparation of liquors.” .
Whereas French pharmacists apparently did not make much of
the new invention,1 it seems to have created quite a stir in Germany.2
Not only was the Original apparatus as designed by Réal ex-
perimented with and its significance as a means of improving the
method of preparation of extracts, i. e. the avoidance of much heat
commented upon, but a variety of improvements were suggested.
Réal himself recognized the disadvantage of a pressure tube 50
to 60 ft. high and, therefore, modified his original apparatus so that
mercury could be used to force the solvent through the finely powdered
and firmly packed drug. 8
Geiger at once (1817) suggested modifications of details 4 like-
wise Buchner 5 and Dingler. 6
The substitution of mechanical pressure for the expensive mercury
was suggested by Dingler,7 that of air pressure by Döbereiner 8 and
Schrader, also by E. Emb':e,9 further by Schubart,10 whereas atmos-
pheric pressure had previously been suggested by Romershausen 11 by
creating a partial vacuum beneath the drug to be extracted. Emcke's
and Romershausen’s apparatus could also be used for filtration.
Romershausen’s press was perfected by Beindorf, 12 and Romers-
1 The Journal de Pharm., which was the representative pharmaceutical journal
of its time, contains in volumes 1 to 27, comprising the years 1815 to 1841, but
three references to IRéal’s filter press (according to the general index). The first by
Cadet has already been mentioned, another by the same editor occurs on p. 468 of
the same volume. A third reference, vol. 5, p. 554, consists merely of the mention
of a paper by Van Mons. However the articles of Boullay and others on displace-
ment appeared in 1833 and the following years. .
Such a treatise on plmarmacy as Baumé's Eiéments de Pharmacie, 3rd ed. of
1818, apparently makes no mention whatever of this new invention that attracted
SO much attention across the Rhine.
2 See references above and those on supposed and real improvements.
S. See Cadet, 1816, Figs. 1 and 2. *
4 Beschreibung der Réal’schen Auflösungspresse. Pamphlet, pp. 22. Heidelberg,
Mohr u. W., 1819; also Magazin für Pharmacie, 9, p. 185, with illustration ; also
Handbuch d. Pharm., 3rd ed. (1830), p. 142. Illustration Fig. 6 of plate.
5 Repert. d. Pharm., 2, p. 363. He suggests an adaptation of the “gewöhn-
liche Schraubenpresse” (See also Geiger, Handb. p. 147) and of the hydraulic press.
See also vol. 3, p. 75, where (p. 76) Sebastian Müller, a watchmaker and mechanic
Of Augsburg is mentioned as a maker of the apparatus.
6 Comp. Repert. d. Pharm., 3, p. 75.
7 See Buchner, Einleitung in die Pharm., 2nd ed. (1822), Part I, p. 252.
8 Trom Insdorff's Neues Journ. d. Pharm., 3, St. 1, p. 1
9 Trom msdorff's Neues Journ. d. Pharm., 1, St. 2, p. 4
buch, p. 146.
10 Neues Journ. f. Chemie u. Physik Neue Reihe, 1, p. 90 ; also Buchner, Einl.
p. 752; also Geiger, Handbuch, p. 146. 4
11 Repert, d. Pharm , 6, p. 316; also Buchner, Einleitung, p. 252; also Geiger.
Handbuch, p. 146.
12 Geiger, Handbuch, p. 146. Illustration Fig. 7 of plate.
58 ; also Geiger, Hand-
4.
hausen himself described 1 (1822) rather complicated apparatus, in
some of which heated air and vapors were utilized. Methods creating
a vacuum beneath the drug without an air pump, viz. by condensa-
tion of alcohol vapor in a closed compartment, were suggested by
Döbereiner and Martenstein.”
None of the numerous contrivances succeeded in displacing the
original Réal apparatus, neither does this seem to have enjoyed
general use at any time.
Reports on experiments with these apparatus for pressure per-
colation were reported,” though this sort of work seems to have
been less popular than the fad of devising new apparatus.
The statement has repeatedly been made that Réal laid the
foundation for the later development of percolation by American
pharmacists, who returned to the simpler technique of the older
process of lixiviation.”
This claim must not be taken without a grain of allowance for
it appears to have been overlooked that percolation in its modern
sense was applied to the extraction of powdered drugs, e. g. the pre-
paration of tannin from nut galls with ether (Pelouze) in a perco-
lator devised by Robiquet (Fig. 3). Moreover, before 1830
Haenle showed that the high column of liquid was by no means
always necessary. He devised a simple percolator.5 Others no doubt
used similar apparatus. Thus Faraday describes how a funnel may
be used as a percolator and how it should be packed. 6
The general interest in this process by French scientists was
revived by the extensive experiments and reports of Boullay, father
and son, in 1833. It was evidently through their reports that
American pharmacists became interested in the subject. Those who
took up the subject were Duhamel, and more particularly Procter
and Squibb.
There can be no doubt, however, that the greatest incentive was
1. 1_Schweigger's Journ. f. Chem. (neue Folge, 4, p. 106; also Geiger, Handbuch,
p. 147.
2 Magaz. f. Pharm., 23, p. 29 ; also Geiger, Handbuch, p. 147.
3. Cadet, de Gassicourt (1816) reports on a number of extracts thus prepared
and the superiority of the products obtained over those made according to the old
way with the aid of continous heat necessary for the evaporation of a dilute first
pºet. Journ. de Pharm., 2, p. 468; transl. by Buchnºr, IRepert, d. Pharm., 3,
D. 7
4 See e. g. Schelenz, Geschichte d. Pharm., p. 658; also
Realencyclopaedie (l. gesamten Pharm., Ból. S., p. 12.
5 Magaz. f. d. Pharm., 11, p. 57; see also Geiger, Handbuch, p. 144.
6 Michael Faraday, Chemical Manipulations.
5
given the development of percolation by making this process officinal
in the U. S. Pharmacopoeia of 1840.
While the above illustrations readily reveal the simple lines along
which the use of the percolator developed in the hands of chemists,
a more detailed account of the development of the art of percolation
Fig. 3. Robiquet’s Percolator.
&l. b. C.
Reproduction of the origi- From Berzelius, Lehrb. d. Reproduction of the “Ver-
nal cut See Bibliography. Chem. (ite Aufi S. Bi. 6, dràngungsapparat” for
p. 314; iiiustrated piate the, extraction of, tannie
1. Fig. 15. See also Bă. acid from nut galls with
io p. 235 ether as illustrated in
y g Gorup-Besanez, Lehrbuch
der organischen Chemie,
vierte Auflage (1872),
p. 566.
in the hands of the pharmaceutical practitioner and manufacturing
pharmacist will be found under the caption Bibliography.
The evolution of apparatus for hot or continuous percolation,
the socalled extraction apparatus of chemists, is so large a subject
that it should be treated by itself.

Choice of
Percolator
General Principles. In order to be able to apply the pro-
cess of percolation to the extraction of drugs with the greatest
success, and with the least possible expenditure of time and materials,
a knowledge of a variety of things is essential.
In as much as drugs vary greatly in their nature and since even
the same drug requires different treatment for different preparations,
variation in the size and shape of percolators is necessary to obtain
the best results. The choice of a percolator depends mainly upon
three things: -
1. Upon the nature of the drug.
2. Upon the nature of menstruum.
3. Upon the kind of percolate desired.
For drugs which are liable to swell, when moistened, especially
with an aqueous or feebly alcoholic menstruum, a conical shaped
percolator is best, as its slanting sides allow an upward expansion
& sº "g
Rººts.
a-º-º:
Fig. 4. Conical Percolator. * Fig. 5. Cylindrical Percolator. *
of the drug. Wherever possible, however, a tall, narrow cylindrical
form is preferable, for the same menstruum must pass through a
greater column of drug and thus thorough exhaustion is insured with
the least amount of menstruum. -
* Cuts for figs. 4 and 5 were kindly loaned by Whiteall, Tatum & Co.




*. 7
This is exemplified in the fact that the U. S. P. calls for a
cylindrical percolator in the preparation of all the fluid extracts,
while in the preparation of the tinctures, etc., with a few exceptions,
simply “a percolator” is designated. The preparations in which the
U. S. P. especially recommends the use of a conical percolator are:
Extract of gentian : Aqueous menstruum, no maceration after packing
drug.
Extract of krameria: Aqueous menstruum, no previous moistening, or
maceration of drug. -
Fluid extract of squills: In this case, the difficulty of powdering the
drug necessitates the use of a coarse powder, No. 20, and the maceration of
the powder for 48 hours in a large excess of the menstruum before packing
it in a percolator. -
Fluid extract of rhubarb : Rhubarb swells more readily than most drugs
because of its loose texture.
Infusion of prunus virginiana: Aqueous menstruum, no previous macer-
ation.
Tincture of lactucarium : Coarse powder packed without previous
moistening.
With strongly alcoholic menstruums or with ether or other non-
aqueous liquids narrow cylindrical percolators should be used, e. g.
in the preparation of oleoresins.
Where a concentrated percolate is desired, a cylindrical percola-
tor is indicated, but where less concentrated solutions are required
as in the preparation of official tinctures, a wider percolator is pre-
ferable for the liquid will pass through more rapidly and yet exhaust
the powder thoroughly owing to the larger amount of menstruum
in proportion to the amount of drug used.
When properly packed in the percolator, the drug should not
occupy more than three-fourths of the height of the percolator.
The degree of fineness of the powder to which the drug should
be reduced depends upon the menstruum to be used and the readiness
with which the active constituents of the drug can be extracted.
For example the difficulty of extracting aconite, requires a very fine
powder, while for rhubarb, a coarse powder will suffice. In general
the more strongly alcoholic the menstruum, the finer the powder,
while aqueous menstrua are better adapted to coarse powders. How-
ever, no hard and fast rule can be laid down, for the adoption of
the various sizes of powders in the different official preparations,
these having been determined from experience and experiment. If a
drug is too coarsely powdered, or not uniformly, complete extraction
Fineness of
Powder
8 *
Moistening and
Maceration
is hindered, and when the powder is too fine, percolation ceases
from agglutination. For concentrated solutions, e.g. fluid extracts,
in which a limited amouut of menstruum should be used, a finer
powder is required while in the case of tinctures where the amount
of menstruum is large, a coarser powder can be employed.
In order to give the dry cellular tissue of the drug a chance to
expand from the absorption of liquid, the powdered drug should be
thoroughly moistened with the menstruum to be used. If the powder
is packed before the complete expansion of the tissue has taken
place, the percolator may become clogged from the subsequent
swelling of the tissues when the menstruum is added.
The moistened drug should be allowed to stand for a period
varying from fifteen minutes to several hours according to the
nature of the drug, a hard, horny drug requiring a longer time than
a drug with a loose texture.
In the official tinctures the moistened drug is allowed to
stand 6 hours before packing, in all cases with the exeption of
tincture of belladonna and tincture of stramonium 3 hours; tincture
of Vanilla, and tincture of gentian compound, 12 hours; tincture of
calumba and tincture of opium deodorized, 24 hours; tincture of
opium, 48 hours. -
The time during which the drug is allowed to macerate after
being packed in the percolator, is 24 hours, with the exception of
those cases in which the time of moistening is more than 6 hours.
In the latter case, the drug is percolated as soon as packed. For
the tincture of galls, neither moistening nor maceration is required.
In the fluid extracts of nux vomica, sanguinaria and squills, the
moistened drug is allowed to stand 48 hours before being packed,
and percolation is begun at once, without any maceration. In all
the other fluid extracts the drug is packed immediately after moisten-
ing and then allowed to macerate for 48 hours before percolating.
The amount of menstruum used to moisten the drug before
packing, depends upon the nature of the preparation to be obtained.
With extracts and fluid extracts, an amount of menstruum varying
from one-fifth to one-half of the weight of drug, is required, while in
the case of tinctures, where a less concentrated solution is to be
made, the drug is moistened with menstruum equal to from one-
twentieth to one-tenth of the weight of drug used.
9
A percolator may be packed either by pouring in the whole Packing
amount of drug at once, as directed by the U. S. Pharmacopoeia,
shaking it down carefully and applying pressure to the surface; or
the powder may be introduced in several portions, distributing and
packing each portion separately. For larger amounts of drug the
latter method is preferable, care however, must be taken to pack
the lower layers less firmly than the upper layers. The firmness in
general, with which a powder should be packed, depends on the
nature of the drug and on the menstruum employed. For aqueous
menstrua, which extract considerable albuminous and gummy matter,
the powder should, as a rule, be packed loosely. For alcoholic
menstrua the powder should be packed firmly. Spongy and loose
textured drugs, which are easily extracted, should be packed more
loosely than hard, difficultly extracted drugs.
If the powder has been properly packed, the menstruum when
added, should descend evenly and at a uniform rate through the
mass. If it descends more rapidly on one side than on another, the
powder has been irregularly packed, and parts of the drug may not
be thoroughly exhausted.
The rapidity with which the percolate sbould be allowed to flow,
will depend entirely upon the amount of menstruum, to be used. A
small amount of menstruum requires slow percolation.
The exhaustion of the drug must be determined by the nature
or peculiarities of the drug operated on, and can best be considered
in the study of the various drugs and their preparations.
Repercolation, introduced by Squibb 1) in 1866, or fractional
percolation, as it is called by Diehl 2) consists of the successive
application of the same percolating menstruum to fresh portions of
the substance to be percolated. Its object is to effect a saving of
alcoholic menstruum and to prepare strong solutions without the
use of heat. For details of the process see Exercise II.
Rate of flow
Exhaustion
Repercolation
In the preparation of fluid extracts by the process of simple
percolation in which a large amount of weak percolate must be
evaporated, the active principles are often so dissociated and split up
during the concentration that they are no longer in their natural
condition, but in a new form which changes their solubilities, making
the preparation something else then the true extract of the drug as
1 Proc. A. Ph. A. 1866, p. 81. -
2 Am. Journ. Pharm., 41, p. 337. ©
10
Continuous
Percolation
it is supposed to be. Evidence of this is found in the fact that a
resinous or oleaginous drug can be thoroughly exhausted by a
menstruum which will permanently hold all its constituents or ex-
tractive matter in solution. But if such menstruum be evaporated,
the addition of the same kind and quantity of menstruum will
not again dissolve the residue and hold it in solution. For example,
a diluted alcohol will exhaust buchu leaves and will hold the oil
while in its natural relations with other constituents of the leaf, in
the same kind of combination that exists in the leaf before extrac-
tion and in such a solution, though very dense, the oil does not
change in odor much, if at all, or more rapidly than the leaf does.
lf such a solution be evaporated until the oil is precipitated and
shows itself as a fully formed oil, the same strength of alcohol will
not redissolve it. Nor will any strength of alcohol redissolve the
whole of the extract. - -
Continuons percolation is a process of extraction by which a drug
is exhausted with a very small amount of menstruum by continuously
vaporizing and condensing the solvent in a specially constructed
apparatus, arranged so that the extract remains in a receiving flask
and the solvent, in the form of vapor, passes into a reflux condenser
and then back into the percolator. For details of the process see
Exercise III.
Fig. 6, Percolator according to Mohr, for continuous extraction.

11
Bibliography. I. While no special effort has been made to
exhaust the subject of percolation bibliographically, the following
abstracts of journal articles will not only be found fairly complete, but
will also prove very useful to students of the subject who care to
persue any aspect thereof more thoroughly.
Cadet, C. L. - 1816.
Filtre-presse de M. Réal. .
Journ. de Pharm., 2, pp. 165 and 192; Itepert. der Pharm., 2,
p. 356.1)
1)
Fig. 7. Original and Modified Réal Filter-Press.
A brief description with illustration of the apparatus.
The body of the extraction apparatus A is made of tin the top of which, being
screwed on, can be removed. It is supported on a tripod. At D and D are
two false bottoms F, between which the material that is to be extracted is
packed. In to the cover of the apparatus, the pipe B, which may be 50 to 60
feet high, is fitted. The countinunication between B and A can be stopped by
means of the stop-cock C. The dish E under the tripod receives the extract.
2) The extraction apparatus C is provided with perforated bottoms at F and F be-
tween which the powdered drug is packed. The solvent is admitted to the
space X by pouring it into the funnel E. The extract is collected in the con-
tainer G. The pressure is secured by filling the cast iron container. A with mer-
cury. . After the apparatus C is charged with drug and solvent, the stop-cock
H is closed and the pipe B also filled with mercury which then forces the men-
struum through the finely powdered and firmly packed drug,
1 With a note by Buchner on page 362.
*

Buchner, J. A. - 1817.
Fernere Nachrichten über die Réalsche Auflösungs-Presse.
Repert. der Pharm., 3, p. 74.
The author regards the “Solution-Presse” as one of the most important
pharmaceutical inventions of the time, because it enables the apothecary to
prepare concentrated liquids without the use of heat or exposure to the air.
The finished product can be obtained with the aid of relatively little heat.
It is reported that the ,Solution Presse” has been made official in all
Belgian pharmacies.
The filter press of “fine English tin” used by him was obtained through
Dr. Dingler. and was evidently made by the watch maker and mechanic
Sebastian Müller, both of Augsburg. •
The larger part of the article is a translation of Cadet de Gassicourt’s
article in the October number (1816) of the Journ. de Pharm. q. v.
Semmelbauer, W. - 1817.
Etwas iber die Réal'sche Auflösungs-Presse und über eine neu-
erfundene Compressions-Maschine, welche jene völlig entbehrlich
machen wird. -
Repert. der Pharm., 3, p. 88. -
In a communication to Buchner, the writer suggests the use of air
pressure as a more practical substitute for the method of securing pressure
employed by Réal.
Doebereiner, J. W. - 1819.
Die Theorie von der Wirkung der Réal’schen Auflösungspresse.
Annalen der Physik, 60, p. 14.
Doebereiner tries to explain the advantages of percolation by assuming
the formation of successive hydrates and the removal of the hydrates by
the motion of the liquid from above down ward, overcoming the capillarity
by which the concentrated solutions of these hydrates are held by the small
spaces within the drug powder.
In a “Zusatz”, Gilbert, the editor of the Annalen reviews, pp. 17–21,
the account given in Geiger’s pamphlet of Réal's “solution press” and of
Romershausen's modification.
Hagen, C. G. v. - - 1819.
Erprobter Nutzen der Filtrirpressen.
Repert. der Pharm., 5, p. 414.
ICxtract from a letter to Prof. Buchner. The Réal “solution press” is
used in several apothecary shops in Königsberg and employed by his son
wherever possible, e. g. in extracting the resin from jalap with the aid of
alcohol. -
Wuerzer, - - - 1819.
Beitrag zur Vervollkommnung der Réal'schen Presse.
Repert. der Pharm., 7, p. 230.
The two principal features of the suggested improvements are
1) The application of faucets below and above the extraction cylinder
to regulate the pressure;
2) The use of a Senguerd stopcock above to allow the liquid remaining
in the pipe to flow out without coming in contact with the exhausted drug.
1. A. The complete apparatus.
& b. The tube, with the Senguerd
stop cock (c., d), into which the
upright pressure tube (not in-
dicated) fits.
e. Lateral tube.
h. Stop cock for percolate.
Fig. 2. Showing working of stop
cock, c, d.
Fig. 3. The Senguerd stop cock.
t
:
:
-s'
Fig. 8. Wuerzer's Modification of Réal’s Filter Press.
Brandes, R. - 1819.
&4.
i
º
#|4 Bemerkungen iber pharma-
ceutische Gegenstände.
Repert der Pharm., 7, p. 234.
Description of a home made
percolator as described by
Tro-umsdorff in his “Journal”.
Fig. 4 gives a perspective view,
Fig. 5 a sectional view of the ap-
4 paratus constructed according to the
principles of Réal.
Fig. 9. Brandes’ home-made Percolator.
See Doebereiner, 1819.






14
Buchner, J. A.
Beschreibung und
Abbildung der von
Herrn Dr. Romershau-
Sen erfundenen Luft-
presse.
Repert. der Pharm.,
6, p. 316.
An abridged account
from Dr. Romershausens
pamphlet. — Descrip-
tion of illustration, p.
321. — Application and
results, p. 323. — Com-
parative experiments us-
ing the air press and the
Ordinary method of ex-
traction.—Rhubarh (tinc-
ture), p. 329,-Cinnamon
(tincture), p. 330. —
Whytt’s Elixir, p. 333.—
Tinctura Ratanhiae Re-
eciana aromatica, p. 334.
— Essentia Pimpinellae,
p. 335.
*/ºr a Pharmacº. 3. V.
1819.
2"º_A^
l
§ §
§
•. s
§
4 \ = < \
Fig. 10. Romershausen’s Air Press.
*/Z/7%armacie A. V/
"
Fig. 11.
º
Romershausen’s Modified Air Press.
f
|
|
The two tin cylinders
B. and C. are mounted
On the Support A. and
are provided with the
COWel’s 1 and 1 (). On the
Support the diaphragm
3 is placed, covered with
a Straining cloth which
is held in position by the
(iiaphragm 4, which in
turn is fastened by the
clasp 5. A third dia-
phragm 6 is used to
cover the substance to
be extracted. The two
cylinders are united by
the tube 7 provided with
a Stop cock. The lower
part of B. is also pro-
yided with a stopper åt
8 in order to allow the
percolate to flow out at
9. The lower section of
| C. is converted into an
air-tight
CO m partment
by the cover 11, which
is provided with an
Opening and stopper at
12: The parts indicated
by 13, 14, 15, 16 and
, - 17 belong to the suction
pump necessary, to cre-
ate a vaccuum.
The suction pump is
Outside of the cylinder .
and the percolate is not
allowed to collect under-
neath the percolator B.
but is at once pumped
into the reservoir C.











15
Beindorf. 1826.
Magaz. f. d. Pharm., 9, p. 185.
* Geiger, Handb. d. Pharm. (1830), p. 142.
º
S.
X
º
&-
=
s
--~
*
--> *
!
.
\\s
-*
-
*
*
Fig. 12. Beindorf’s Modifications of Réal’s and Romershausen’s Apparatus.
Fig. 6. The modified Réal filter press is so mounted that it can be tipped at
a convenient angle for filling and emptying. -
Fig. 7. The modified Romershausen apparatus supplying a much more compact
and, therefore, more serviceable tool. *. -











16
Boullay, père & fils. 1833.
Sur la filtre-presse de Réal, son mode d'action, ses enconvêniences,
moyen plus simple et généralement applicable pour parvenir au meme
bout.
Journ. de Pharm., 19, pp. 281—291. 1)
Although Réal's filter-press is based on the only method that will effect
complete extraction of vegetable powders with water, “it is but little used,
no doubt, because of its inconveniences.” (p. 281.) -
The disadvantages, the long tube or column of mercury, and the other-
wise unnecessary strength of the extraction apparatus and the difficulty of
procuring tight joints, are all due to the pressure which is unnecessary.
(p. 282.) -
The advantage of Réal’s process over that of expression lies in the ease
with which the last drop of liquid containing the dissolved substance can
be extracted; also in the use of the smallest possible quantity of liquid
necessary, and in the clearness of the products. (p. 285.) -
Six rules to be observed in percolation with water. (p. 288.)
The principle underlying Réal’s process has previously been employed.
1) In the cafetière of Dubelloy, which differs from Réal’s filter-press only
in the absence of the pressure tube. It has all the advantages of Réal’s
filter press and none of its disadvantages. (p. 289.)
2) In the filter of Dumont used for the discoloration of syrups by
means of carbon. (p. 290.)
3) In the washing of precipitates on filters. (p. 290.)
Introduction of the phrase “procédé par déplacement.” (p. 291.)
Robiquet, — 1833.
Journ. de Pharm., 19, p. 322.
At the meeting of May 2 of the Pharmaceutical Society of Paris, at
which Boullay read his first communication, Robiquet exhibited an appara-
tus “designated to operate as indicated by Mr. Boullay.” He recalls the
fact that he spoke of this apparatus in connection with his and Boutron-
Chalard's paper and states that similar apparatus have been used at the
Paris School of Pharmacy “for a long time.”
Boullay, père & fils. 1833.
De la méthode de déplacement, en prenant pour type le quin-
Quina. Discussion des formules nombreuses proposées pour chacun
des médicamens dont cette écorce fait partie. Choix fondé sur les
1 Am. Journ. Pharm., 5, p. 318; Ann, der Pharm., 7, p. 314, with critical
comment by Geiger, p. 318. See also p. 322 for extract of minutes of meeting of
#. 1888 of Paris Pharm. Soc., at which this paper was read, also comment, by
O piquet.
17
résultats exacts et rigoureux que la methode de déplacement permet
Seule d’obtenir.
Journal de Pharmacie, 19, pp. 393—425.”
Phrase “méthode de déplacement” introduced. (p. 394.)
&
Experiments on cinchona. (pp. 395–421.)
Conclusions 1–8 arrived at as to the process. (p. 421.)
3rd. That the high column of water proposed by Réal has no other
effect than to render the apparatus less applicable.
6th. That the filter of Réal, minus the pressure, is nothing else than
the “cafetière” of Dubelloy.
8th. That the process of displacement should be generally adopted for
preparing preparations involving small amounts of liquid, because the first
products are very concentrated and since the strength of the following per-
colates decrease very rapidly in strength. Conclusions 1—18 concerning
cinchona preparations. (p. 423.)
Geiger, P. L. 1833.
Comment to Boullay, père et fils, 1833.
Ann. der Pharm., 7, p. 318.
As editor of the Annalen, he calls attention to his pamphlet on the Sub-
ject and also to his handbook. He also criticises the use of the funnel
suggested by Boullay for general purposes as percolator.

Robiquet. 1834.
Note sur l’acide méconique.
Journ. de Pharm., 20, p. 79.
On p. 83 the author describes the apparatus to which he *
has previously referred, viz. in connection with his report on \
Aº 3
the bitter almond oil.
It is an ordinary water bottle into which the long percolator
K is ground with emery. The material to be extracted is kept in
place by means of a plug Of cotton.
Simonin. + 1834.
Extrait d'une letter sur la méthode de déplacement,
adressés à M.M. les rédacteurs.
Journ. de Pharm., 20, p. 109.
Observations on the percolation of rhatany and sarsapa-
rilla. -
*-*- Fig. 13.
Robiquet’s
* Am. Journ. Pharm , 5, p. 318.
Apparatus.
18
1834
Simonin.
Journ. de Pharm., 20, opposite p. 128.
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Percolators by——
Fig. 14.


19
Boullay père & fils. 1835.
Considerations nouvelles sur la méthode de déplacement. Appli-
cations particulières au Ratanhia et au Gayac. Appareils.
Journ. de Pharm., 21, pp. 1–22. -
The experiences of Souberan, Limonin, Felix Boudet, Buchner, Dublanc,
Pelletier and Pelouze with the method of displacement are indicated (p. 3):
Boullay, P. F. G. 1835.
Note relative aux observations publiées dans le dernier numéros
du Journal de Pharmacie, par E. Robiquet, a l'occasion de la
méthode de déplacement.
Journ. de Pharm., 21, p. 188. -
A rejoinder to Robiquet in which Boullay disclaims having made any
false pretenses, but claims that they were the first to apply the method to
“a very large number of medicinal substances” which are otherwise altered
more or less by prolonged evaporation, etc. They emphasize once more the
“inutility, in most operations, of the pressure column applied in Réal’s
apparatus.”
Dausse, – - 1835.
Sur un nouvel appareil pharmaceutique portatif, pour la prépa-
ration de tout extrait, soit alcoolique ou aqueux, réunissant la
méthode de déplacement, la distillation et l'évaporation au bain-
marie. par M. Dousse ainé, pharmacien, et exécuté par M. Oberlin.
Journ. de Pharm., 21, p. 369.
Merely a brief description of the apparatus, without illustration, being
an extract from a mémoir presented to the society. This is followed by a
report of a committe of the Society.
Robiquet, — 1835.
Sur la méthode de déplacement appliquée au traitement du café,
de la noix de galle, de la cochenille, de l’ipécacuanha et des cantha-
rides.
Journ. de Pharm., 21, p. 113.
The author critisizes Boullay’s claims to priority, having used the pro-
cess of percolation for 5 or 6 years in his private laboratory, in his factory
and for 2–3 years at the school. Indeed, since 10 years he has used long
“alonges” mounted on a “bocal” with the aid of a “bouchon” for ether
extraction, principally of cantharides.
Four years ago he requested Lemire to have made at the glass works
of Choisy-le-Roi very long and “étroites” “alonges” with a “robinet” at the
lower end. Later Acloque had them made for him at another glass works
without stop cork. These apparatus had been exhibited at the School and
since been kept in stock by Acloque and sold under the name of Robiquet’s
apparatus. -
With Geiger he agrees in that he believes that the pressure in Réal’s
apparatus is far from being useless. (p. 116.)
20
A review of the work previously done with the aid of this method of
extraction on *> -
Coffee. (p. 117.)
Carmine from cochenille. (p. 118.)
Nut galls. (p. 120.)
Garances. (p. 122.)
Cantharidine from cantharides. (p. 123.)
Soubeiran, – 1836.
On lixiviation of vegetable and animal substances.
Bull. gen. de Therp., -, p. ––.
Am. Journ. Pharm, 8, pp. 221–228.
Displacement is lixiviation employed on vegetable substances. Boullay is
credited with having introduced the method into pharmacy. Dausse’s work
on 80 different substances was not published. Soubeiran, continuing the
expts. of Guillermond, worked with 71. Comments on the fineness and
moistening of the powder, and its compression in the apparatus. For water
and alcohol, Boullay’s apparatus, for ether that of IRobiquet should be used.
Duhamel, A. - 1838.
Boullay’s filter and system of displacement with observations
drawn from experience.
Amer. Journ. Pharm., 10, pp. 1–17.
An essay based largely on the papers of Messrs. Boullay and a paper by
Guilliermond, also on the experience of the author.
Historical and descriptive. (pp. 1–6.)
Expts. with cylindrical and conical percolators. (p. 7.)
“Hany's process” applied to feeding
menstruum. (p. 8)
Percolation applied to decoctions. (p. 9)
Comparison between maceration and
displacement. (p. 12.)
Percolaton “first” applied to resinous
substances. (p. 16.)
Percolation “first” applied to mineral
substances. (p. 17.)
Drugs exptd. with :
“Gray” bark. (p. 6.)—Jalap. (p. 7.)—
Cinchona. (p. 10.)—Rhatany. (pp. 10 & 15.)
— Dork. Soapwort. Liquorice. Senna.
Digitalis. Cicuta. (p. 10.)—Gentian. (p. 11.)
—Rhubarb. (p. 11 & 15.)—Burdock. Sapo-
naria. (p. 11.) — Sarsaparilla. (p. 12.) —
Uva Ursi. (pp. 12, 14 & 15.)—Buchu. (p. 14.)
— Digitalis. Boneset. “Bark.” Pareira
brava. Resins with sand. (p. 15)—Myrrh.
Benzoin. Aloes. Guaiacum. (p. 16.) Fig. 15. French percolator.

21
Duhamel, A., and Procter, Wm. Jr. º 1839.
Observation on the method of displacement.
Amer. Journ. Pharm., 11, pp. 189—201.
The authors call attention to the fact that whereas “in France this
method has been extensively applied” (it was made official in the Codex
Pharmacopée Française of 1835, p. 199) “in this country it is hardly
known, much less applied” and make a plea for its introduction into the
next Pharmacopoeia. (p. 189.)
Reports on experiments with the following drugs, with frequent reference
to Boullay’s work.
Extracts: Chamomile, digitalis cicuta, stra monium, belladonna, colocynth
(comp.). *
Tinctures: Colchicum, Senna, lobelia, rhatany, opium, capsicum, cubebs,
valerian, rhubarb, “bark’’, colocynth, serpentaria, hellebore, ginger,
and galls; also myrrh, guaiacum, benzoin, and asafoetida.
Infusions: “Bark”, rhubarb, digitalis, belladonna, chamomile and
gentian.
Syrups: Rhatany, uva ursi, senna, boneset, buchu, pareira brava, Sar-
saparilla, rhubarb, Senega, squill.
List of preparations of French Pharmacopoeia, 1835, made by percola-
tion. " (p. 199.)
Basford, J. K. 1858.
i Basford’s compound percolator. - *
San Francisco Bulletin, –, p. —. [Am. Journ. Pharm., 30,
p. 81; Proc. A. Ph. A, 7, p. 63.]
A description of the percolator mentioned above, but no illustration
(i.e. in A. J. P.).
Graham, I. J. 1858.
The process of percolation or displacement: its history and
application in pharmacy.
Proc. A. Ph. A., 7, pp. 285–294. [Am. Journ. Pharm. 31, p. 354.
A review of the earlier work of Boullay and Guillermond, and criticism
of some directions given by several writers. “If I have a just conception
of the principle upon which it is based, it is, that the substance to be
treated, and the menstruum, should be presented to each other under such
circumstances; that each particle of the solvent shall be fully charged with
soluble matter, and immediately displaced with another particle, to become
in its turn more or less saturated in like manner; and if all the conditions
of the process have been properly observed, these saturated particles collect
and escape from the apparatus, as containing to the fullest possible extent
all that the menstruum is capable of taking up, and even more than could
be taken up by any other means.”
Squibb, E. R.
The process of percolation.
Am. Journ. Pharm., 30, pp. 97–102.
Rules concerning
1) Moistening of drug.
2) I)imensions of percolator.
3) Packing of percolator.
4) Addition of menstruum.
5) Rate of percolation.
Description of an autoimatic percola
1858.
Fig. 16.
Squibb’s Automatic Percolator.
a—Stan (l.
b—Percolator, stral) ped at e, and provided
with glass cork at f.
d—Reservoir for menstruum, which is
Syphoned by tube j, and provided with
air tube k of much larger diameter than
feeding syphon j.
tor and of well-tube percolator.
Fig. 17.
Squibb’s Well-tube Percolator.
b—Percolator, mounted on stool
a, and I) ovided with well-tube c
surrounded by tow or straw, covered
by blanket d, fastened to well-tube.
g—Funnel for admitting menstru-
ll lll .
e—Syphon for removing percolate
from well tube c to recipient f.


23
Committee A. Ph. A.” 1859.
Report on the revision of the Pharmacopoeia: Percolation.
Proc. A. Ph. A., 8, pp. 220 and 239.
A brief account of the introduction of the “process of percolation” into
the U. S. P., 1840, its extended use in the edition of 1850, and a “proposed
general description of percolation” for the ed. 1860. (Appendix B., p. 239).
Parrish, E. 1859.
On the use of funnels in displacement. Q
Am. Journ. Pharm., 31, p. 327–330.
The author favors the funnel recommended by Graham.
Procter, Wm., Jr. 1859.
On percolation or displacement.
Am. Journ. Pharm., 31, pp. 317–324.
“The object to be obtained in practice by Boullay’s theory is this: a
solvent, poured on the top of a powder consisting partially of soluble matter
contained in a cylindrical vessel and supported on a porous diaphragm
descends from layer to layer by capillary attraction, and its on gravity,
exerting its solvent power on each successive layer until its power of solu-
tion is exhausted, after which it continues to descend by the pressure of the
superincumbent fluid, until forced out through the diaphragm into the vessel
below, a saturated solution; this process continuing until the soluble matter
is so far removed from the powder that the liquid by the contact becomes
less and less charged with the soluble matter until exhausted. But to gain
this result, it is absolutely necessary that the substance treated shall be in
a uniform p ow der, and that the capillarity or p or ous n e s s of
the mass of powder be not destroyed by a ny cause whate ver,
for, on the fact of the slow, regular, a n d even descent of the
sol vent, from on e horizontal layer to the next without side
channels or circuits, caused by irregular powdering or imperfect packing,
depends the success of the process.”
Details as to fineness of powder (p. 318), packing of drug (p. 321) and
experimental reports on gentian, senna, rhubarb and columbo.
Signoret, M. 1861.
Percolation under strong pressure.
Répertoire de Pharmacie, –, p. —. Amer. Journ. Pharm., 33, p. 319.
Description of a pressure pump that can be attached to four percolators.
Wine of cinchona was prepared in 20 minutes.
* E. Parrish, I. J. Grahame & C. T. Carney.
Redwood, T. 1864.
On the preparation of tinctures, by per-
colation, maceration, and the automatic
process, with remarks on the new method
introduced in the British Pharmacopoeia,
and suggestions for its improvement.
Pharm. Journ., 23, pp. 533–548. [Proc.
A. Ph. A., 12, p. 72.]
Percolation sanctioned in the Edinburgh
Pharmacopoeia of 1839, p. 533.
Subject of percolation first brought to
attention of Br. Ph. Soc., pp. 533 and 544.
Discussion of U. S. P. process, p. 535.
York Glass Company’s percolator, p. 539.
See also Procter's editorial comment on this
article in A. J. P., 36, p. 382.
Fig. 18. York Glass Company’s Percolator.
Squibb, E. R. 1865.
Proposed economy of alcohol in percolation, as applied to the
extracts and fluid extracts of the Pharmacopoeia.
Proc. A. Ph. A., 13, p. 201. [Am. Joui. Pharm., 38, p. 109.]
The author proves by experiment that the cylindrical percolator is far
superior to the conical percolator, in that a larger yield of dry extract is
obtained from the former. He also gives a description and the dimensions
of the percolators (p. 212).
Giles, R. W. 1866.
On a new macerating apparatus.
Pharm. Journ., 26, p. 219. Proc. A. Ph. A., 15, p. 140.
A description of an apparatus exhibited at the British Pharm. Conference:
eight conical percolators are so arranged that the percolate from the first
becomes the menstruum for the second etc., so that each portion of drug
is macerated and percolated eight times.
Squibb, E. R. 1867.
Repercolation applied to the cinchonas, as a method of economiz-
ing alcohol in the exhaustion of drugs.
Proc. A. Ph, A., 15, pp. 391—399.
A study in repercolation, as applied to the extraction of cinchona bark.

Diehl, C. L. 1869.
On fractional percolation.
The Pharmacist, —, p. —. [Am. Journ. Pharm., 41, p. 337.]
The author reports on the application of Squibb’s process of “reperco-
lation,” which he designates “fractional percolation,” to senna and rhubarb.
For details see under Laboratory Exercises, No. II. For Procter's criticism,
see A. J. P., 41, p. 295.
Squibb, E. R. 1872.
Note on a new form of percolator for fluid extracts, tinctures etc.
Proc. A. Ph. A., 20, pp. 182—192.
The author claims that the chief merits of this new form of percolator
are due to the fact that it embraces maceration with percolation to any
extent desired; that it controlls the rate of percolation and is independent
of the packing.
a—The tumbler-shaped percolator.
b— Di k Of flannel.
c — Disk of flannel with + incission stretched
Over the
e — Well-tube.
d—Disk of filter paper.
h—Space for drug covered by
i —Disk of muslin.
j —Cover with trap.
U 4.----| 37 f—Syphon is ept ill position by g and k.
!), \ ++-: 1 — Receiving flask.
Fig. 19. Squibb’s glass well-tube percolation.
Ratanhia (p. 4), Syrup, tincture, decoction.
Gayac (p. 13): Extracts, resin, tincture.
A discussion of Geiger’s criticism in the Ann. der Pharm. (p. 15.)
Description of combination displacement and distilling apparatus.
(p. 19.) -
Prio it y quarrel with Robiquet. (p. 21.)


26
Stoddart, W. W., & R. L. Tucker. 1872.
The tinctures and wines of the British Pharmacopoeia.
Pharm. Journ., 32, p. 213. [Pharm. & Chem. Record, –,
p. 252; Proc. A. Ph. A., 21, p. 194.]
The authors point out the * F * The diagram represents the form
advantages of percolation of percolator, ABCD, prepared
tº • , , 4-5 by Mr. Deane (PHARM. JourN.
ove mace ation, and of the H #85 having º: inclined to
cylindrical over the conical the base line at an angle of 82°.
percolator. If the vertical height be 24 inches,
The form of percolator a a column of water at EF would
º - y exert a pressure on the base CD,
illustrated by diagram, p. equal to 12:384 ounces for ever
214. square inch. º,"; the lº
& Cº s?: •lzin o' the pressure wou e only 6.192
Spontaneous” packing, ounces, and at H only 3:096 ounces,
p. 214. t or one-fourth of the whole.
Table of results, p. 215. G #-d
Discussion, p. 216. Fig. 24. S. & P. 's diagram showing
pressure in percolator.
Moore, J. B. 1874.
Comments upon the process of percolation.
Amer. Journ. Pharm., 46, p. 55 ſ—558.
The author offers criticisms upon the official process of percolation of
1860, and maceration and percolation of 1870.
Campbell, S. 1875.
Percolation.
Proc. A. Ph. A., 23, p. 599.
The author states that the funnel, as a percolator, is most available
for ordinary use in all drug stores. He also describes a glass percolator
designed and patented by L. Dursse of Baltimore.
Hildebrand, E. C. H. 1876.
Adjustable supports for funnels, percolators, etc.
Amer. Journ. Pharm., 48, pp. 400–402.
“The sides of an equilateral triangle coming as tangents in contact
with the periphery of an inclosed circle, mark out in the latter three arcs of
equal lengths; further, by drawing a line through the triangle parallel to
on of its sides, an equilateral triangle of smaller size is formed, relating to
a correspondingly smaller circle.”
A

|
A B and C D – Wooden staves placed in a divergent position and united by
cross pieces 1, 2, 3 etc. A part of each cross piece is cut Out, leaving ºn Open
space of 60°. With the next cross piece this forms the opening for the reception
of the vessel. With the divergence of the staves the Openings grow larger. Each
opening is further adjustable by interposing quadrangular staves as shown in Fig. 3.
r
*
*
-
º
\,
/
}
*.
i
º
º
“The side of the triangle next to the stand is provided with a ridge a of such
shape as to form with its trestle a longitudinal notch for the reception of those
pieces of different widths of thin sheet iron, which are placed across the triangle to
adjust the opening to a given vessel.”
Fig. 20. Hildebrand’s adjustable support for percolators.
Proctor, B. S. 1877.
Modified percolator.
Pharm. Journ. and Trans., 36, p. 641–642. [Amer. Journ.
Pharm., 49, p. 372.]
The author suggests the addition, to the usual cylindrical tube and
receiver, of a cylinder of tin plate or other suitable material, closed at each
end, fitting loosely within the percolation tube, the object being to get a
slightly increased hydrostatic pressure. The cylinder floats in the liquid
and, the space between it and, the percolator being narrow, a head of 6 or
8 in. is obtained with a small quantity of liquid.
Reming con, J. P. 1877.
On a percolating and filtering stand.






28
Amer. Journ. Pharm., 49, pp. 589—692. [Proc. A. P. A., 26,
p. 52.]
The construction and advantages of this stand become readily apparent
from the accompanying illustration.
sº sºlº
º, *
gº w ºf -----
ºi $
º Š *
: A
ſ
§§s
62 SDC sº
º |
| |
c/
Slſsºs.WSSS
jS$
º
fº
| º
SSSSSSSSSSSSSSSSSSSSS$
§ºš
§
Fig. 21. Remington’s percolator stand.
a — Uprights to which are fastened the
l) and c – LX rackets, the longer limb of which is placed horizontally and per-
forated. By means of these perforations the
d — Horizontal strips provided with a slot can not Only be fastened but ad-
justed
e–Cross-pie “es, also provided with slots to admit of lateral adjustment by
means Of Screws.
Diehl, C. L. & 1878.
Co-operative experiments on fluid extracts.
New Rem., -, p. 132. [Proc. A. Ph. A., 26, p. 104.]
The author invites cooperative experiments in simple and fractional
percolation, both of which he describes, for Com. On Pharmacopoeial Re-
vision of the A. Ph. A.




































29
Squibb, E. R. 1878.
Fluid extracts by repercolation.
Proc. A. Ph. A., 26, pp. 708–754. [Proc. A. Ph. A., 26, p. 97.]
A review of percolation as a pharmacopoeial process and a plea for the
process of repercolation as exemplified in the difficult extraction of cinchona.
Selection of menstruum, p. 712.
First percolation, p. 714.
2nd, 3rd and 4th portions, p. 716.
Tabulation of results, p 719.
Menstruum II, p. 721.
Conclusions, p. 724.
Criticism of Lloyd’s work on Cimicifuga, p. 726.
Description of apparatus, p. 733.
Description of process, p. 743.
Fluid extracts by percolation, table of, p. 753.
Lloyd, J. U. 1879.
On the conditions necessary to successfully conduct percolation.
Proc. A. P. A., 27, p. 682.
• A review of the principles and history of percolation.
Laws governing shape of percolator, p. 698.
Condition of material to be exhausted, p. 200.
Rosenwasser, N. 1881.
A new process of percolation a new
percolator.
A mer. Journ. Pharm., 53, pp. 567—572.
[Proc. A. P. A , 30, p. 32.]
With the use of the apparatus illustrated
below, the author claims to overcome several
of the disadvantages of the percolators then
ll] llSG”.
Fig. 1. Percolator closed in position and con-
nected with reservoir C.
Fig. 2. The inverted open percolator in position
for packing.
I3 and D — Porous diaphragms.
C— Drug.
Fig. 22. The Rosenwasser Percolator.

30
Fairthorne, R. F. 1882.
A new displacement apparatus.
Amer. Journ. Pharm., 54, pp. 236—239. [Proc. A. P. A., 30, p. 32.]
Fig. 23. Fairthorne’s displacement apparatus.
A — Egg-shaped percolator. B — Cover. G — Airpump.
By first, creating a partial Vacuum in the charged percolator, the menstruuni -
can be draw n into it, from
J– The container for the menstruum. After maceration, percolation may be
started by exhausting the air from the •
C— Receiver.
Berry, —. 1883.
A pressure percolator.
Am. Journ. Pharm., 55, p. 587,
According to Maisch this percolator differed from Rosenwasser's perco-
lator principally in the material used in its construction.
Calvert, J. 1883.
Simple apparatus for making ethereal tinctures etc. by percola-
tion.
Proc. Cal. Phar. Assn., 14, p. 40. [A. J. P., 55, p. 269.]
*

illustration is otherwise selfexplanatory.
31
Flasks 1 (reservoir) and 2 (percolator)
are ordinary quart douche bottles; flask 3
(receiver) is a common quart bottle.
Oldberg, O.
A set of standard dimensions for simple percolators.
ſº
The
iññāſū
sºlºfsº
º
º
ºº::
ſº
ſ |
º §
* * *
ſ:
º
hº
|ſº
§
wº-
Włll!!!!Milliºlyſt
Sº tº gºt tº
#
º
iº
Fig. 24. Calvert’s Percolator.
1884.
Proc. A. Ph. A., 32, p. 390. [A. J. P., 56, p. 541; Pharm.
Rundsch., 2, p. 210.]
3. In I #. Depth lº #. #. Length of 3.
& terna lameter ept iam’ter Diam’ter|Length o
# Agrºte Lººſ Diameter of Body at of Shoul *:::" of Stem of Stem | Rubber #
* pacity. 7 at the Top.] the Shoul- der N & at the at Mouth Tube. #
in der. Throat. [or Exit.
. #3 |g| 5 || 5 || 5 || 5 || 5 |3| = |s|F |: ; ;| = | 5 || 5 ||
§ to |É | 3 || 5 || 3 | #| 3 |#| 3 |É # |#| 3 |É| 3 | #| #
...|C. c. gº 5 || 5 || 5 || 5 || 5 || 5 ||5|| 3 |5| 3 |5 # |5|| 5 || 5 || 3
as ºr gº Uſe 3. tº r: (r. ; : :" 6t. wº © (a # ºn
* = |g g t § § § { . § § | - § | -
E. wº * tº {º {r, 7; . . : * 3. &
X 90 3 fl.ºz. 15o 5.09| 3o 1.18r; 25 .984. 4. . . 57.39||1. 181|Io; .39412) .472, 20cl 7.87
2| 1.5ol 5 “ 18o 7.09| 36|| 1.417 3o 1,181; 6 .236||30}1.181|Io! .394|12 472| 24of 9.45; 2
3| 24o 8 “ 21o 8.27| 42| 1.654 35| 1.378 & .315|Soir. 181 Io; .394.12 .472; 28o I 1.92 3
A| 360 ra “ 24o 9.45| 48] 1,899 40| 1.575; Io .394.39||1.:81jio .394/12} .472; 320|12.60| 4
. 5| 53o 18 “ |27oiro.63| 54; 2. 126|| 45| 1.772}12| .472|35||1.373:13; .52215; .591 360|14.17| 5
6| 74o 25 “ |300||11.8; 6o 2.362 5ol 1.968; 4} .551.35||1.378;13 .512.15 .591) 4oo!15.75|| 6
7| 1,24o 42 “ 360|14. 17| 72 2.835 6o 2.362|16: .63c.35|x.378|13 512|I5] .591; 48o 18.89 7
8| 1,960 66 “ 420, 16.53| 84 3.307| 7o 2.756; 18; .709:35||1.378; 13 512, 15 .591 $6022.03|8
9| 3,000|Ioo “ 48o 18.89 96 3.7So 8ol 3.150.jzoi .787;35||1.378;13 512; I 5 ,591 éºlºg23 9
1ol 3,78o 8 pts. 540|21.25. Io9| 4.252 9o 3.543|22; .866|35||1.378:13 5I2; 15 .59 I 7.628.35 IO
11| 5,700 12 “ |6oojz 3.62; 120 4.724| Iool 3.937|24: .94535||1.378/13 512; I 5 '59: 8ooi 31.5oll r
12| 7,600 16 “ |66o 25.98; 132 5.197 II of 4.331 25; I.o.2435 1.3%;3 .512) I Si .591; 88o34.65||12
13| 9,850] 21 “ 72028.35] 144, 5,670| 120' 4.72428; 1.19235||1.378:13 512}.15} .591, 96037.80|=
14|12, 5ool 26 “ i78o36.71 156 6.142| 130| 5.1 1813, I. 181135||1.378113 512/15] .5911164olºo.95|14




32
The author criticises the dimen-
sions of the average make of per-
colators found in the market and
i|
|
: gives the detailed dimensions for
: # percolators as they ought to be
| #
º
º
according to his ideas. The ac-
companying cut reveals the general
style of the percolator.
©º
.º
---
sdº-º:
º.;.i
º
º
:
§
Fig. 25. Oldberg’s standard Percolator.
Haliberg, C. s. 1884.
Simultaneous fractional percolation, with notes on some fluid
extracts. *
Proc. A. Ph. A., 32, p. 392.
g By making fractional percolation “simultaneous” the author points out
that much time may be gained. -
Cummings, H. T. 1884.
A study of percolation.
Proc. A. Ph. A., 32, p. 398.
A detailed criticism of Rosenwasser’s paper (see 1882).
Rosenwasser, N. 1885.
Percolation — Experiments and answers to criticisms.
Proc. A. Ph. A., 33, p. 399.
A reply to Cummings criticisms.
Zoeller, E. V. 1886.
Stop-cocks for percolators.
Am. Dr., 15, p. 103. [Proc. A. Ph. A., 34, p. 298.]
The use of a metal “sprinkler” top from perfume bottles is suggested
for regulating the flow of liquid from percolators.






Bedford, P. W. - 1886.
Percolation: A study for young clerks.
Pharm. Rec., 6, p. 19. [Proc. A. Ph. A., 34, p. 298.]
A general review of the subject with several illustrations.
Colcord, J. W. 1886.
Does the method of percolation prescribed by the Pharmacopoeia
yield the best results? g
Proc. Mass. Pharm. Assn., 5, p. 170. [Proc. A. Ph. A., 34, p. 298.]
The author objects to the “preliminary maceration” as directed by the
U. S. P. and suggests alternate maceration and percolation as productive
of better results.
Snow, H. W. 1887.
Percolation.
Pharm. Rec., 7, p. 6. [Proc. A. Ph. A., 35, p. 10.]
A historical review of the development of percolation in America and
the U. S. P. also a description (illustrated) of the percolator devised by W.
H. Allen of Detroit.
Anderson, O. S, 1887.
What are the best proportions for a percolator?
Pharm. Rec., 7, p. 53. [Proc, A, Ph, A., 35, p. 10.]
Criticisms on Snow's paper,
Allen, W. H., 1887,
The best proportions in a percolator,
Pharm. Rec., 7, p. 66, [Proc. A., Ph. A., 35, p. 10.]
Turther discussions of the papers by Snow and Anderson.
Maben, T. 1887.
A simple method for ºper-
colation under pressure.
Pharm. Journ., 46, p. 941.
[Proc. A. Ph. A., 35, p. 10.]
The use of the vacuum pump
in increasing the rate of per-
colation when desired.
a) The vacuum or suction
pump. -
b) An ordinary York Glass
Company percolator.
“An extra pressure of 250
mm , or a total pressure of
one and a third atmospheres
is ample for ordinary percola,
tion.”
Fig. 26. Maben’s Apparatus for Pressure
Percolation,

34
Dieterich, E. - 1888.
Percoliren, auch Deplaciren oder Wer-
drängen genannt.
Pharm. Centrh., 29, p. 168.
A description of the Christ-Dieterich percola-
tor.
º
- - - - - - - - -
*.
**.*. --> *
%
%
%
Ž
a) Vessel of 3 l. capacity, for the drug.
b) Filter,
c) Superantant liquid.
d) Stop cock for the regulation of the flow.
f) Reservoir for automatic supply of menstru-
ll Ill.
g) Stop cock.
h) Cover.
i) Rack fastened to wall.
!
%
*
i
*
* -- -- ºr * - -
7.
%
E
Pig. 27. Qhrist-Dieterich Percolator.
Lloyd, J. U. 1888,
Maceration with percolation,
West, Drugg, 11., p. 159, [Proc. A. Ph. A., 37, p. 336.]
The writer criticises Ince's objections to preliminary maceration,
Marpmann, G. 1888.
Bereitung der Fluid-Extracte.
Pharm. Centrh., 29, p. 507.
Description of a percolator illustrated
by the accompanying cut.
1) Reservoir for menstruum.
2) Pressure flask.
3) Percolator.
Fig. 28. Marpmann’s Percolator.



* * - * 1888.
Der Marpmann'sche Percolator.
Pharm. Centrh., 29, p. 603.
Editorial comment on Marpmann’s article with special reference to the
articles of Hoffmann (1884) and Dieterich (1888).
Marptmann, G. - 1888.
Fluid-Extracte.
Pharm. Centrh., 29, p. 615.
A reply to the above editorial in which Marpmann disclaims any
or gin-uliſ Y.
Phillips, C. W. 1888.
New pressure percolator.
I’harm. Rec., 8, p. 213. [Proc. A. Ph. A., 37,
p. 342.]
Description of a homemade pressure percolator.
A. Ordinary bottle.
13. Glass tube covered at (H.
(X. tº { tº 4 & J. • ‘ II.
I). Rul) ber tube.
I'. Jºu Inuel.
K. Menstituum under pressure.
Fig. 29. Phillips Pressure Percolator.
Ince, J. - 1889.
Percolation.
Pharm. Journ., 48, p. 666. [Proc. A. Ph. A., 37, p. 336.]
“The method of previous maceration (B. P.) in a closed vessel and sub-
sequent transferrence has the threefold disadvantage of being unnecessary,
wasteful and messy.”
Diehl, C. L. 1889.
Pharm. Rundsch., 7, pp. 25 and 60. [Proc. A. Ph. A., 37,
p. 336.]
An illustrated review of the subject of percolation as understood in the
U. S. suggested by the article of Marpinann in the Pharm. Centralhalle,

36
Eckford, J. W. - - - - - 1890.
A review of the various methods of percolation. -
Proc. A. Ph. A., 38, p. 79. [A. J. P., 62, p. 531.]
A brief review of the papers of Hinsdale, Rosenwasser, Cummings,
Thompson and Colcord.
Arny, H. V. 1892.
Economic percolation.
, Proc. A. Ph. A., 40, p. 169.
A description of apparatus designed to prevent, as far as possible, the
loss of alcohol or other volatile solvent.
--- - —ll— 1—
Fig. 3O’. Volatile Fig. 3O’’. Army’s Fig. 30”. Screw-joint
Liquid Per- “‘Compact Per- percolator and
colator. colator. * * - receiver.
Whereas the average loss according to the official process was 16.2 p. c.
(see table, p. 170), the average loss, when apparatus Fig. 1 was used,
amounted to only 5.7 p. c. (see table, p. 172). An attempt to recover the
alcohol left in the marc “by pumping air by means of an atomizer bulb . . . .
into the space between the percolator cover and the marc” resulted in an
average loss of 18.4 p. c. - -




37
Haliberg, C. S. N. W 1893.
The peerless percolator.
West, Drugg., 15, p. 46. [Proc. A. Ph. A., 41, p. 383.]
Another return to pressure percolation. The accompanying cut is
largely selfexplanatory.
Fig. 31. Hallberg’s Peerless Percolator.
Seifert, C. A. - 1893.
- Interrupted or suspended percolation versus continued or regular
percolation. - - - -
Proc. Cal. Ph. Assn., -, p.—, [Proc. A. Ph. A., 41, p. 475.]
Bird, F. C. J. 1894.
Laboratory notes.
Pharm. Journ., 54, p. 158. [Proe. A. Ph. A., 43, p. 508.]
The author recommends the adoption of the process of repercolation for
Ex. cocae liq, and Itesina podophylli by the B. P.

38
Forrest, J. A. 1895.
A convenient arrangement for continuous percolation.
Pharm. Journ., 55, p. 538. [Proc. A. Ph. A., 44, p. 376.]
The principles and technique will be readily grasped by glancing at the
accompanying illustration. -
Fig. 32. Forrest’s Arrangement for Continuous Percolation.
Smith, H. D. F. 1897.
The effect of temperature upon percolation.
Proc. A. Ph. A., 45, p. 245.
Comparative experiments on opium, nux vomica, cinchona, stramonium
conium and belladonna showed 1) that there was practically no difference
in the amount of menstruum necessary to exhaust the drugs to the same
degree; 2) that cold percolation lessens the amount of extractive in the
finished product; 3) that the percentage of active constituents is about the
same in the finished preparations.
“From these experiments I believe the cold percolation process offers no
practical advantage to a pharmacist over the process of percolation at
ordinary temperature.”
*º
1897.
Percolation.
(). & D., 50, p. 922. [Proc. A. Ph. A., 45, p. 376.]
“The claim made by the “Am. Dr.” that the credit of making percola-
tion an official process is due the U. S. P., is met by a counterclaim in the
‘C. & I).’ that this credit really belongs to the Edinburgh, Pharmacopoeia.”

39
Fig. 33.
The above out taken from the 1842 edition of “Christison's Dis-
pensatory” shows the percolators contemplated by the Edinburgh Pharma.
Copoeia,
1) shows a percolator covered with calico at 0;
2) shows a percolator with a stopcock:
8) the percolator arranged for pressure percolation.
Remington, J. P. 1897.
Improved percolate dropper.
Merck’s Report, 6, p. 219. [Proc. A. Ph. A., 45,
p. 377.]
A new percolate dropper made of block tin said to be
an improvement over the “ordinary sprinkler-top arrange.
ment.”
34. Improved Percolate Dropper.
Brown, A. E. - 1897.
Rapid preparation of tincture of iodine.
Proc. Alabama Ph. A., 1897, p. 15. [Proc. A. Ph. A., 46, p. 745.]
The author recommends percolation.


40
\
Kelly, D. C. - - 1897.
Comparative experiments on repercolation.
Proc. Kansas Ph. A., 1897, p. 40. [Proc. A. Ph. A., 46, p. 683.]
From the use of the ordinary process of repercolation in the preparation
of 50 p. c. tinctures of gentian, uva ursi and squill, the conclusion is drawn
that repercolation does not completely exhaust the drug.
Musset, F. 1897.
Preparation of fluidextracts by repercola-
tion.
Pharm. Centralh., 1897, p. 862. [Proc.
A. Ph. A, 46, p. 681.] |
Recommends repercolation for all fluidextracts,
with the apparatus as shown in illustration.
Opposes the use of fine powders, preferring the
T º No. 3 powder of the Pharm. Germ. (passing
U
through two m. m. meshes). Process consists of .
macerating drug in a covered vessel; placing
/ menstruum in the percolator; pouring in the drug
and stirring to form a thick magma; then per.
|-----------------→3' colating Without packing,
Fig, 35. Repercolator for
fluid extracts,
Norris, G. B. 1897,
Influence of temperature on percolation.
Proc. Kansas Ph. A., 1897, p. 41. [Proc. A. Ph. A., 46, p. 684.]
Experiments on the preparation of 50 p. c. tinctures of belladonna, gel-
semium, Valerian, sarsaparilla, and senna by the U. S. P. process of perco-
lation, at 0° C., 20° C , and 38° C., show that the extraction is more com-
plete at higher temperatures.
Sayre, L. E. - 1897.
A problem of drug extraction by percolation.
Drugg. Circ., 1897, p. 212. [Proc. A. Ph. A., 46, p. 685.]
A continuation of a previous article. Repercolation is insufficient to
totally exhaust drugs in making 50 p. c. tinctures.
Benyschek, H. - - 1898.
Preparation of infusions by percolation. - -
Pharm. Post., 1898, p. 759. [Proc. A. Ph. A., 47, p. 437.]
Recommends maceration followed by percolation in preparing infusions.
Experiments on infusions of ipecae, digitalis, senega and ergot.


4].
- catford, J. v.
Automatic repercolation.
1ses,
Chem, and Drugg., Aug. 1898, p. 271. [Proc. A. Ph. A., 47,
p. 386.]
/ ,->
Fig. 37. Catford's Automatic Repercolator. - B his
Cowley, R. C. 1898. ic
Percolation under pressure. ; Pl =
Pharm. Journ., Oct. 1898, p. 418. [Proc. A. re
Ph. A., 47, p. 385.]
The author does not advocate the use of pressure
in percolation but for exhausting certain mucilaginous A p
or finely powdered drugs he recommends the apparatus -------- •= ** * *
shown in the accompanying illustration. gº;22%2:22%.
An apparatus to simplify repercolation.
It consists of 4 glass tube percolators con-
Inected end to end by means of corks cut
as shown at B. The receivers consist of
several small bottles, adjusted to hold a
definite quantity corresponding to the
reserve portion of the percolate. These
bottles are connected as shown at A.
C is a feeding bottle regulator.
Fig. 37. Cowley’s Pressure Percolator.

42
Kemp, D. S. - w 1898.
Water bath percolator. -
Chem. and Drugg., 1898, p. 981. [Proc. A. Ph. A., 47, p. 389.]
An apparatus for percolation requiring a hot menstruum.
Nunn, A. W. 1898.
Percolation under pressure. z e
Pharm. Journ., Oct. 1898, p. 371. [Proc. A. Ph. A., 47, p. 384.]
Pressure is produced by means of an ordinary bicycle pump.
Weber, Wm. - 1898.
Superiority of maceration over percolation for making tinctures.
Drugg. Circ., 1898, p. 216. [Proc. A. Ph. A., 47, p. 381.]
More certain and uniform products are obtained by maderation in the
preparation of such weak galenicals as tinctures.
Wolff, D. J. 1898.
Moistening of powders.
Am. Drugg., 1898, p. 36. [Proc. A. Ph. A., 47, p. 382.]
Directions are given for a convenient method of moistening powders
preliminary to percolation, together with the advantages of this method.
Bernard, J. E. 1899.
Improved percolator. -
Merck's Report, 1899, p. 220. [Proc. A. Ph. A., 47, p. 387.]
A, percolator.
B and H, right angled, threaded flanges.
C, tight fitting, threaded cover.
E. receiver forming tight joint at H.
P, a tube, W, a porous or perforated
septum. -

43
Cohen, A. I. - 1899.
Pressure percolator.
Merck's Rep., 1899, p. 4. [Proc. A. Ph. A., 47, p. 383.]
of /f
rºſºfº. III. |Zººſ ſ ſº.,,,
|iftſ/,
(ſ/|} #%/.
gº
& C B ) le *
Sº
}*
AE)
i
s:S * * * *&
ºà3.**
º
:*: ºº
...? i—Plz
|\\ |- -:
Af
º
t
A
Fig. 39. Pressure Percolator.
A pressure percolator whose construction is simple, easy and inex-
pensive.
à is the percolator, a well tinned can.
1, two oblong holes, cut at opposite sides.
b, a block of hard wood with hole at c center.
o, a spout of a small tin funnel.
d, a diaphragm of hard wood with a hole
g at center in which a rubber stopper
h is fitted.
f, a series of furrows to conduct liquid to center.
i, a short glass tube with end thickened at k.
l, a rubber tube to conduct liquid to
m, the graduated receiver.
m, n, blocks of wood to support diaphragm.
Pressure is produced by connecting o with an elevated reservoir con-
taining the menstruum.
























44
Edel, F. 1899.
Maceration vs. percolation. -
West Drugg., 1899, p. 57. [Proc. A. Ph. A., 47, p. 381.]
A reply to Weber's article. See 1898.
Wood, J. R. - • 1899.
Syphon percolator. -
Pharm. Er., 1899, p. 359. [Proc. A. Ph. A., 48, p. 399.]
A device to avoid the inconvenience of
raising and lowering the siphon-tube and
receiver in regulating the flow of siphon per-
colators. It consists of , two corks, held to-
gether by a pin as shown in illustration. The
function of the top piece is to prevent the
tincture from flowing out in a jet, and cause
it to fall back into the receiver in drops.
Fig. 4.O. Wook’s Syphon Percolator.
Eberle, E. G. - 1900.
Expeditious mode of moistening the powdered drug.
Drugg. Circ., 1900, p. 11. [Proc. A. Ph. A., 48, p. 398.]
The powder is placed in an ordinary covered can, menstruum added
and the mixture stired. A few glass stoppers are then placed in the can
and the contents shaken thoroughly. Advantages: thorough moistening
without evaporation. The glass stoppers prevent, lumping of powder.
Jacobin, J. - 1901.
s Use of shredded wood to prevent clogging.
Pharm. Post., 1901, p. —. [Proc. A. Ph. A., 50, p. 684.]
The use of alternate layers of “excelsior” and drug is recommended to
prevent clogging when percolating drugs of an adhesive nature like opium, etc.

45
Remington, J. P. Jr. 1901.
Apparatus Stand.”
Am. Journ. of Pharm., 73, p. 19.
A neat, convenient and easily adjust-
able device for supporting percolation
apparatus. Two of the stands as shown
in the illustration can be connected by
two parallel horizontal, double tubes ar-
ranged so as to slide up and down the
upright tubes and made secure by thumb
screws at each end. An illustration of
such an apparatus is given on page 20.
The ring clamps instead of being all in
one piece, as in the ordinary stands, are
made in two parts, and therefore permit Fig. 44. Apparatus stand.
of universal adjustment in three directions.
Sackett, C. W. & 1901.
Automatic percolator cut-off."
Drugg. Circ., 1901, p. 195. [Proc. A. Ph. A., 50, p. 683.]
|
~~i=>~~~- * = **ºra ---, -- ---
Fig. 41. Sackett's Automatic Cut-off. g
The automatic cut-off shown in the illustration is recommended for the
purpose of cutting off the flow of percolate when a certain portion has
accumulated in the receiver.
A is a tube arranged to move like a scale beam on
E, the support, and is connected by
B, a rubber tube, to the percolator.
() is a vial containing one-half. ounce of mercury.
D is an empty vial attached to one arm of .1. To operate, fill the
bottle containing the float, D, with a volume of water equal to the amount
of percolate to be reserved. Adjust the float so that the tube A is nearly
horizontal. Empty the bottle and allow percolation to begin. As soon as
D floats, the percolate will be diverted into the other bottle.
* Made by the Remington Mfg. Co., Philadelphia.


46
Andrews, E. A. # 1902.
Preparation.of liquid extract of belladonna B. P. by a process
of repercolation.
Pharm. Journ., April 1902, p. 336.
Stedem, F. W. E. 1902.
Manipulation in case of resinous drugs.
Bull. Pharm., 1902, p. 235. [Proc. A. Ph. A., 50, p. 682.]
Specific directions for percolating resinous and oleoresinous drugs in
preparing tinctures and fluidextracts.
Linton, W. H. 1903.
Percolation as applied to the liquid extracts of the B. P.
Pharm. Journ., 1903, pp. 389, 420, 457. [Proc. A. Ph. A., 51,
p. 622.]
A review of the history of percolation as applied to the extraction of
drugs and a record of the results of a series of experiments on the liquid
extracts of coca and cimicifuga and limiment of aconite. The general con-
clusion is drawn that two-thirds of the total soluble matter is extracted in
the weak percolates and is consequently subjected to a fairly high tempera-
ture during concentration. A reduction in the amount of menstruum used
in moistening the drug is recommended.
Ruhle, H. F. - 1903.
Percolator support.
Proc. Pa. Pharm. Assoc., 1903, p. 145. [Proc. A. Ph. A., 52,
p. 485.]
A simple wall device for a permanent percolator support.
Hooper, E. S. 1904.
Apparatus for collecting percolate in fractions.
Pharm. Journ., July 1904, p. 140. [Proc. A. Ph. A., 53, p. 506.]
The apparatus consists of
A, a narrow glass tube fitted into
B, a U-tube, the other limb of which
contains a glass tube to serve as a pressure
tube.
P, the percolator is connected to the
lowest side tube. When U-tube B is filled
the percolate will pass into the 2nd
U-tube, etc.
Fig. 42. Hooper’s Fractional
Percolator.

47
Lloyd, J. U. Q 1904.
U. S. Patent No. 777.115.
An apparatus for making extracts etc., whereby the substance held in
solution is not changed by heat; by which the alcohol or other menstruum
is used over and over again and in which the menstruum remaining in the
waste may be recovered.
Fig. 45. Lloyd’s Percolator.
* -
Ҽ
Schmitt, L. 1904.
Percolation vs. maceration.
Journ. pharm. chim., 1904, Nos. 1–4. [Proc. A. Ph. A., 52,
p. 483.] •
A report on the results of a series of experiments on the relative efficiency
of maceration and percolation, Percolated tinctures formed larger precipi-
tates than those made by maceration.

48
Lenz, W, * o
A hot-extraction and pressure percolator,
Ber, d. D. Pharm, Ges., 15, p. 137,
Fºº { º
Mºhº —l Sºº
sº º
*=ºmmiſſy
Illinºiſſãº
Hillſ. Tilſillſº
|
Fig. 46. Lenz’s Percolator.
This jacketed percolator is specially designed to carry
on simple percolation at any desired temperature, by pass-
ing hot water or steam through the jacket. The cover is
tight which prevents evaporation. The cover has three
openings, one for a thermometer, one for a pressure gauge
and the third is a Fahrrad valve through which a pres-
sure of two or three atmosphere can be maintained in
the apparatus by means of an air pump.
Eldred, F. R. 1906.
Assay percolator.
º
Journ. Am. Chem. Soc., 28, p. 187. [Proc. A.
Ph. A., 54, p. 593.]
A small percolator for use in drug assaying. A plug
of cotton is packed tightly below the constriction A.
The glass stoppers on both ends allow the drug and
solvent to be thoroughly shaken without loss, before
percolating.
1905,
Fig. 47. Eldred’s Assay Percolator.















49
Laboratory Exercises. Carefully select a percolator of such a size
so as to be about 94 filled by the quantity of drug used. The choice of a
comical or cylindrical percolator, will depend upon the drug used, and the
nature of the menstruum and percolate. g
A perforated cork, bearing a short glass tube should then be tightly
wedged into the funnel-end, from within, until the end of the cork is even
with the outer edge of the orifice. The glass tube must not extend above
the inner surface of the cork and should project about 2 inclies beyond the
outer surface. To the end fasten a closely fitting rubber tube, about 4
longer then the percolator itself. The rubber tube, the end of which should
contain a second short glass tube, may be clamped to the side of the per-
colator during maceration by means of a rubber band, so that the end of
the tube is above the surface of the menstruum in the percolator.
TO prevent the powdered drug from falling through the funnel-
end, place a notched cork, Fig. 48, in the neck and cover with a
thin layer of cotton; or a tuft of cotton abové may be used which
should be slightly pressed into the neck of the percolator. The
cotton should be moistened with a few drops of the menstruun.
so as to aid in the passing of the first part of the dense per-
colate. It is sometimes found convenient to place a thin layer of clean
white sand on top of the cotton to hold it in place. Care
should be taken not to press the cotton in too tightly. It
should almost cover the bottom of the percolator with a .
thin layer and fit loosely into the upper part of the neck .
Glass wool may be used in place of cotton. It has the ad-
vantage of retaining its spongy condition on becoming wet.
Place the substance to be percolated, which must be uni-
formly powdered and of the fineness directed in the formula,
in a shallow dish, pour on the specified quantity of menstru-
um, aud stir thoroughly with a spatula until uniformly
moistened. This can usually be determined by the absence of
lighter colored lumps. Pass the moist powder through a
coarse sieve, transfer to a sheet of thick paper and pour the
whole quantity from this into the percolator. The powder
should be shaken down lightly and allowed to remain thus
for a period varying from a few minutes to several hours
according to directions. After this pack the drug uniformly
with a aid of a suitable plunger of the shape of the common
potato-masher, Fig. 49. If desirable, especially where larger Fig. 49.
Fig. 48.
Exercice I.
Method of
Simple
Percolation

5()
quantities of the drug are used, the powder can be introduced and packed
in portions.
After the powder has been properly
packed, place a circular piece of filter
paper, slightly larger than the upper
layer of drug, upon the upper surface
of the powder, weighing it down with
pebbles or glass stoppers, or with
weights especially made for this pur-
pose, Fig. 50.
Then gradually add a quantity of
menstruum, care being taken not to
disturb the powdered drug, sufficient Fig. so.
to completely saturate the whole pow-
der and to leave a layer above. Having covered the per-
colator with a rubber percolator cover Fig. 51, or a piece
of glass, allow to macerate for the directed time.
To start percolation, lower the rubber tube from the
side of the percolator, and introduce the glass end into a
tared or graduated bottle (Fig. 52) to receive the percolate
The rapidity of percolation may be increased or decreased
by raising or lowering this ~
receiver. A layer of men- 2, ; #
struum must be constantly ſ: (#iºi
maintained, above the pow-
2 * * * * der. Great care should al-
Fig. 52. ways be taken in ever to
allow the menstruum to disappear below the surface of the powder This
prevents the drawing of air into the interstices of the drug and the sub-
sequent formation of fissures, through which the menstruum would flow,
instead of percolating through the powder.
Fig. 51.
Fig. 53 shows two percolators, A improperly packed and B properly
packed and set up. º
The exhaustion of the drug can be determined by a chemical test for
One or more of , the active constituents, by tasting or more rarely by
the color.
Prepare one or more fluid extracts and tinctures by the method of
percolation as given above, recording the amount of drug used, the
amount of menstruum used, the amount of percolate obtained, the amount.
of finished product, and the time of actual percolation. Compare method of
percolation as given in U. S. Pharmacopoeia, p. LI.

**
Fig. 53. Properly and improperly packed percolator.
Weigh out 32 parts of the drug in the official powder and divide into
4 equal portions of 8 parts each.
Moisten one portion of the drug with the proper menstruum, pack and
macerate (see Exercise I and U. S. P.) and percolate. Reserve the first 6
parts of percolate and continue the percolation until the drug is exhausted
separating the percolate received after the reserved portion into fractions
of about 8 parts each.
The amount of menstruum used for moistening should be in the same pro-
portion as given in the U. S. P.
Exercise II. –
Repercolation.

Exercise III. —
Continuo s
Percolation.
Moisten a 2nd portion of 8 parts of the drug with the first fraction of
the weak percolâté—the portion that was obtained next after the reserved
percolate-pack, macerate and percolate as before, supplying the percolator
with the remaining fractions of the weak percolate in the order in which
they were obtained, and finally with fresh menstruum until the drug is
exhausted. Reserve the first 8 parts of the percolate, and collect the weaker
percolate into fractions of about 8 parts each. - s
Pereolate the 3rd and 4th portions of 8 parts each of the drug in the
same way as the 2nd portion. - * , , -- -
- . . . . . . . º
Finally mix the four reserved percolates together which would make 30
parts of finished fluid extract. Having corked, labelled and numbered the
bottles containing the fractions of weak percolate set them away until the
process for the same drug is to be resumed. When the same fluid extract
is to be made again, repeat the process as with the 2nd portion. *
Apparatus:-The essential parts of a continuous percolation apparatus
consist of a cylindrical percolator, a receiving flask and a condenser. An
f) apparatus can be readily constructed as shown in Fig.
| 54. A is an ordinary conical percolator of such a size
; that it will not be more than two-thirds filled with
the drug to be extracted. B is a round-bottom flask,
containing a twice perforated stopper, through one
hole of which a glass tube connects the flask to the
percolator. Through the second hole is inserted the
glass tube C which also passes through the cork
stopper in the top of the percolator. The end of the
condenser D is also inserted through the latter cork.
All cork connections should be tightly sealed with
gelatine. - -
Method : – In extracting a drug, e. g. the pre-
paration of an official oleoresin, pack the drug into
the percolator A as in simple percolation (see Exer-
cise I) without previous moistening or macerating.
Pour on menstruum gradually through the condenser
tube, until about 50 c. c. has collected in the receiver
13 and there still remains a layer of menstruum above
the drug in the percolator. Apply heat to the pre-
viously warmed water-bath so that the menstruum
will distill through the tube C and back into the
percolator, when it will again pass through the drug
Continue the percolation, regulating the rate of distil
Fig. 54.
lation so that it about equals the rate of flow of the percolate, until the
drug is exhausted. By carefully regulating the rate of distillation, so that
some menstruum always remains in the flask B, Overheating of the residue
is prevented. - -
With the above apparatus, prepare one or more of the official oleoresins.

The Soxhlet extraction apparatus differs from the continuous percolation
apparatus, described in Exercise III, in that it involves,
principle of a siphon. The apparatus consists of a
cylindrical percolator, Fig. 55, in which the pow-
dered drug is poured in loosely but not packed. The
top of the column of drug, upon which a circular piece
of filter paper should be placed, should be lower
than the top of the siphon. The menstruum is
poured through the condenser, and should be of
sufficient quantity to fill the siphon and leave a layer
of the liquid above the drug, higher than the top of .
the siphon. The siphon will then start to flow
and will continue until all the menstruum in A has
been siphoned into the receiving flask tightly fastened
to the end of the percolator by means of a cork. By
applying the heat of a water-bath the menstruum
will distill through the tube and will flow from the
condenser back into the percolator. When the
level of the liquid is above the top of the siphon, per-
colation will again take place, the liquid being again
siphoned into the receiving flask. This operation can
be repeated until the drug is exhausted. Prepare an
oleoresin with the Soxhlet apparatus.
Bxercise IV. —
º • * > Continuous
in addition, the Percolation
With a Soxhilet
Extraction
Apparatus.

f j4
suppleMENT.
Beck, - ------------
Percolating Stand. - " - * , -
Caspari-Treatise on Pharmacy, 1901, p. 144.
; :
.
f
º
º
l
ºt.
f
º
-
º
º
º
#
i.
§~ -~º #-ſºli
Fig. 43. Percolating Stand.
This stand admits of simultaneous multiple operations. It can be
changed by means of thumb screws to suit various heights of bottles. The
length of the base-board is 42 inches, the width 12 inclies and the extreme
height of the stand 36 inches. The supports for percolators and funnels
are formed by means of cross pieces suitably hollowed out and secured by
screws passing through the slot in the cross bars.
—-º-A
-
- ERRATTA.
On page 31 Oldberg (1884) is given credit for first havings uggested the
use of tall, conical percolators. These were in reality first suggested by
Diehl,” although they are still commonly known as the Oldberg percolator.
* Troc. A. Pb. A., 27 (1 S79), p. 727.

MONOGRAPHS
1. Popular. German Names. This popular pamphlet has been revised
- twice by its author, Dr. Fr. IIoffmann. r ().50
+4. *A
2. Reagents and Reactions known by the names of their authors.
Based on the original collection of A. Schneider; revised and en-
larged by Dr. Julius Altschul; translated from the German by Dr.
Richard' Fischer, Asst. Professor of Practical Pharmacy at the
University of Wisconsin. Although imperfect in many respects, this
compilation has proven a convenient aid in the laboratory and oil
- the desk. A revision is now in progress. Out of print.
3. Popular Scandinavian Names. A compilation of popular Swedish
names of drugs and medicines by Harold Bruun, with formulas for
the preparation of a number of gaienicals not generally found in
American reference works. This list is also being revised. Copies still
on hand can be had for $0.15
4. Early Phases in the Development of Pharinaceutical Legis-
lation in Wisconsin. An account by Edward Kremers of the evolu-
tion of the first local pharmacy law in Wisconsin with the documents
on which the account is based. Pamphlet; pp. 43. $0.50
5. Some Cuban Medical Plants. While collecting plants in Cuba
during the year 1895 and 1896, Prof. R. Combs had his attention
directed to numerous plants of the island used as domestic remedies.
Pamphlet, pp. 20. $0.15
6. History of the Art of Distillation and of Distilling Appara-
tus. By Oswald Schreiner. Pamphlet, pp. 59, with 65 illustrations.
* • $0.35
7. The Crude Drugs and Chemicals of the United States Phar-
macopoeia (1890) and the Preparations Into Which They
Euter. Iły W. O. Richtmann. Pamphlet, pp. 55. Now being ";
- 0.25
8. Progress in Alkaloidal Chemistry, 1903. A collection of ab-
stracts by H. M. Gordin. Pamphlet, pp. 40. $0.30
*9. The Sesquiterpenes. A monograph by Oswald Schreiner. Brochure,
pp. 130. $1.00
10. Progress in Alkaloidal Chemistry for 1904. By H. M. Gordin.
Brochure, pp. 94. $0,70
11. The Volatile Oils: 1904. By I. W. Brandel. Brochure, pp. 51.
l $0.35
12. The Balance. By I. W. Brandel and Edward Kremers. Brochure,
pp. 49, with 48 illustrations. Intended primarily as a text for students.
$0.35
13. A Review of the Literature on the Estimation of Alkaloids
. . for the Year 1905. By W. A. Puckner, Brochure, pp. 17. $0.20
14. The Naming of Carbon Compounds. By W. A. Puckner.
Brochure, pp. 17. $0.20
\
.**
Medical library
MONOGRAPHS.–Continued.
15. Volksbenennungen der brasilianischen Pflanzen und Pro-
dukte derselben in brasilianischer (portugiesischer) und der von
der Tupisprache adoptirten Namen. By Theodor Peckolt. Brochure,
pp. 252. $2.06 -
16. Pinkroot and its Substitutions. By W. W. Stockberger. Bro-
chure, pp. 64, with 2 plates and text illustrations. -$0.50,
17. Progress in Alkaloidal chemistry for 1905. By H. M.
Gordin. Brochure, pp. 120. $0.75
1s. The volatile oils: 1905. By I. W. Brandel. Brochure,
pp. 42. -- $0.35
-
19. A Review of the Literature on the Estimation of Alkaloids
for the Year 1906. By W. A. Puckner. Brochure, pp. 21. $0.25
20. Progress in Alkaloidal Chemistry during the Year 1906.
Dy H. M. Gordin. Brochure, pp. 96. $0.65
21. Plant Pigments. By I. W. Brandel. Brochure, pp. 72. $0.60
22. Percolation. A brief historical account, followed by a statement of
general principles, a complete bibliography and laboratory exercises.
Intended primarily for students of pharmacy. By I. W. Brandel and
Edw. Kromers. Brochure, pp. 54. $0.75 -
* *.
(In course of preparation.) *-
—The Volatile Oils: 1901–1903. By I. W. Brandel. The manuscript
is practically completed. When published, these annual reviews will
constitute a complete supplement to G.-H...-K. “The volatile oils.” ;
***
Asºº
—ur
BIBLIOGRAPHIES. ‘
1. Chemical Bibliography of Morphine. From 1875 to 1897, with.
an index of authors and subject index. By H. E. Brown. Pamphlet, .
- pp. 60. - $0.40
2. Santonin. Bibliography, with abstracts of methods of production
etc. From 1830 to 1897. By A. Van Zwaluwenburg. Pamphlet,
pp. 11. $0.10
3. Bibliography of Apiol. From 1855 to 1896. By A. Van Zw a-
lu wenburg. Pamphlet, pp. 4. $0.05.
4. Bibliography of Spirit of nitrous ether, and ethyl nitrite.
Up to 1899. By W. O. Richtmann and J. A. Anderson.
Brochure, pp. 180. $1.00
5. Bibliography of aromatic waters. From 1809 to 1900 incl. -
By W. O. Richtmann. Brochure, pp. 219. $1.00 .
6. Literature on Medicinal Plants and Drug Plant culture.
By Albert Schneider. Brochure, pp. 24. $0.40