EXCHANGE 
 
Some New Condensations with Para* 
 
 para-bis (Dimethylamino)-Benzo- 
 
 hydrol (Michler's Hydrol) 
 
 DISSERTATION 
 
 SUBMITTED IN PARTIAL FULFILLMENT OF THE RE- 
 QUIREMENTS FOR THE DEGREE OF DOCTOR OF 
 PHILOSOPHY IN THE FACULTY OF PURE 
 SCIENCE OF COLUMBIA UNIVERSITY 
 
 / ..,. JJII.1T 
 
 BY 
 
 AARON RUDERMAN, B.S., M.A, 
 
 1922 
 
Some New Condensations with Para 
 
 para-bis (Dimethylamino)-Benzo- 
 
 hydrol (Michler's Hydrol) 
 
 DISSERTATION 
 
 SUBMITTED IN PARTIAL FULFILLMENT OF THE RE- 
 QUIREMENTS FOR THE DEGREE OF DOCTOR OF 
 PHILOSOPHY IN THE FACULTY OF PURE 
 SCIENCE OF COLUMBIA UNIVERSITY 
 
 BY 
 
 AARON RUDERMAN, B.S., M.A, 
 
 1922 
 
TO THE MEMORY 
 
 OF 
 MY FATHER 
 
 50208G 
 
ACKNOWLEDGMENT 
 
 The author desires to express his indebtedness to Professor Marston 
 Taylor Bogert, who suggested this work and under whose direction it was 
 carried out. Whatever merit this research may have is due to his con- 
 structive criticism and invaluable assistance. 
 
SOME CONDENSATION REACTIONS WITH PARA-PARA-BIS 
 (DIMETHYLAMINO)-BENZOHYDROL (MICHLER'S HYDROL) 
 
 Introductory 
 
 Fosse 1 has shown that ^-substituted secondary aromatic alcohols, in- 
 cluding Michler's hydrol, condense with one of the methylene hydrogens 
 in compounds containing the -CO-CH 2 -CO- grouping, with elimination 
 of a molecule of water and the insertion of the alcohol residue in place of 
 the hydrogen removed. 
 
 Inasmuch as the hydrogen of the imino group in imides of dibasic acids 
 often behaves in a way recalling that of the hydrogen in reactive methyl- 
 enes similar to the above (for example, compare the Gabriel imide reac- 
 tions with those of malonic ester), it was thought of interest to test this 
 experimentally, particularly in view of the fact that Mohlau and Heinze 2 
 found it impossible to effect such condensation with any amides except 
 urea, and that Reitzenstein and Breuning 8 have reported that the hydrol 
 reacts with isatin (an isomer of phthalimide) by removal of nuclear and 
 not of imide hydrogen. The experiments of Mohlau and his co-workers 4 
 have indicated, further, that the hydrol condenses with primary or second- 
 ary aromatic amines in alcoholic solution with formation of the corre- 
 sponding leucauramines. Kern 6 and Noelting, 8 using cone, sulfuric acid 
 
 * Fosse, Chem. Zentr., 1907, I, 1696; C. A., 2, 823, 2387, 2689 (1908); Ann. chim. 
 phys., [8] 18, 400, 503,531 (1909) '.Bull. soc. chim., [4] 7, 229 (1910); Compt. rend., 
 150, 179 (1910); -4*11. chim. phys., [9] 13, 118, 154 (1920); C. A., 15, 1711 (1921). 
 
 2 M6hlau and Heinze, Ber., 35, 359 (1902). 
 
 Reitzenstein and Breuning, Ann., 272, 257 (1910). 
 
 M6hlau and others, Ber., 33, 799 (1900) ; 34, 882, 3384 (1901) ; 35, 359 (1902). 
 
 * Kern, Ger. pat., 27,032, 1883. 
 
 * Noelting, Ber., 24, 3127, 3136, 3139 (1891). 
 
6 
 
 as solvent, noted: that the reaction then follows a different course, nuclear 
 hydrogen being removed and not that of the amine groups, the products 
 being triphenylmethane derivatives and not leucauramines. This differ- 
 ence in behavior is somewhat akin to that of benzaldehyde and aniline 
 which yield benzal-aniline in alcoholic solution, but diamino-triphenyl- 
 methane in presence of mineral acid. 
 
 On dissolving phthalimide and the hydrol in alcohol and warming the 
 solution, a condensation product was obtained, crystallizing in greenish- 
 yellow plates, m. p. 186.7 (corr.). This gave phthalic acid and leucaur- 
 amine on hydrolysis with dil. mineral acid, and on warming with dil. 
 potassium hydroxide solution added the elements of water with formation' 
 of the amidic acid. Boiling the latter with dil. hydrochloric acid split 
 it into phthalic acid and leucauramine. 
 
 C 6 H/' N 
 N CCK 
 
 (/CO.NRH 
 NH+HO.R > CH4< >N.R 3 
 
 CH 
 + R.NH 2 R = -CH(CeH 4 .N(CH,) 2 ) 2 
 
 These facts justify the conclusion that the hydrol residue is in union 
 with nitrogen and not with carbon in this product. 
 
 When cone, sulfuric acid was substituted for alcohol as solvent in this 
 reaction, and the solution was warmed at 100, a colorless product was 
 obtained on precipitation with alkali, which proved to be a labile form 
 of the compound (m. p. 186.7) mentioned above, and into which it changed 
 slowly on standing, or more rapidly when heated. On dissolving the col- 
 ored form in sulfuric acid and precipitating rapidly by alkali, a colorless 
 oil separated which soon congealed to the yellow form again. 
 
 Phthalimide contains the 2 chromophoric carbonyl groups attached 
 to the benzene nucleus just as they are arranged on one side of the anthra- 
 quinone formula, but with an imino group on the other side instead of a 
 second benzene nucleus. A similar relationship exists between the iso- 
 meric isatin and phenanthraquinone. Phthalimide is colorless, whereas 
 isatin is a deep yellowish-red. Anthraquinone is clear light yellow, but 
 phenanthraquinone is orange. The arrangement of the carbonyl groups 
 in isatin is, therefore, of greater chromophoric effect than that in 
 phthalimide. Those auxochromes which have the most potent batho- 
 chromic action in the anthraquinone group, NHAryl>NHAlkyl>NH 2 , 
 appear to be the ones with greatest influence also in the phthalimide 
 molecule, since the amino-phthalic acid derivatives generally show decided 
 color (yellow). Acylation of the amino group of course discharges this 
 color, since the acylamino group is not ordinarily an auxochrome. 
 
7 
 
 Kauffmann and Beisswenger 7 found that 3-amino-phthalimide exists 
 in 2 tautomeric forms, one yellow with green fluorescence, and the other 
 colorless with violet fluorescence. Such tautomerism might be explained 
 conceivably by assuming a migration of hydrogen from the imino group 
 to an adjacent carbonyl, giving a -C(OH) : N- structure. Such an hy- 
 pothesis, however, scarcely can apply to the ^-alkyloxy phthalanils, C 6 H 4 - 
 (CO) 2 N.C 6 H4.OR, which Pitui and Abati 8 report as also occurring in 
 colored (yellow) and colorless modifications, and these investigators, 
 recognizing the fact, conclude that this difference cannot be accounted 
 for on the basis of difference in chemical structure, but may be due to a 
 dimorphism similar to that of benzophenone. 
 
 Although but one form of isatin is known, Pummerer 9 has succeeded 
 in producing aniline derivatives of the 2 tautomeric structures, 
 
 X N V 
 4 ^ j>C. 
 
 .NH.C 8 H 6 
 (Yellowish brown) (Violet) 
 
 If the tautomeric forms of phthalyl leucauramine observed by us are 
 similarly related structurally, the colorless modification would be repre- 
 sented by Formula I, and the colored by Formula II or III 
 
 O/COv /C(OHk /CO 
 
 N.CHR 2 ,CflH 4 < >NH:CR 2 ,C 6 H 4 < >N:CR 2 ,C 6 H 4 < >O 
 
 ^C<y ^ CO ' X::N.CHR 
 
 I II III IV 
 
 On the basis of these structures, one would expect Formula I to repre- 
 sent the more stable (colored), rather than the less stable (colorless) 
 tautomer. 
 
 There remains the further possibility that the colored form may be 
 related to the colorless as indicated in Formulas I and IV. This is a change 
 of linking of the type postulated by Baly and Desch 10 in aceto-acetic com- 
 pounds, and by Stewart 11 in ethyl pyruvate, a kind of tautomerism which 
 they have termed "isorropesis," and to which they have attributed the 
 property of selective absorption. If then Formula IV is a correct repre- 
 sentation of the colored modification, we are dealing with a compound 
 possessing absorption bands in the visible part of the spectrum which are 
 due to isorropesis. 
 
 In favor of Formula IV it may be remarked that it contains a : C: N- 
 grouping, resembling the chromophore of the Schiff bases. On the other 
 hand, it has been found in the case of the quinophthalones 12 that the first 
 
 7 Kauffmann and Beisswenger, Ber., 36, 2495 (1903). 
 
 8 Pitui and Abati, ibid., 36, 996 (1903). 
 
 9 Pummerer, ibid., 44, 338 (1911). 
 
 10 Baly and Desch, /. Chem. Soc., 87, 766 (1905). 
 
 11 Stewart, ibid., 89, 489 (1906). 
 
 Eibner and others, Ber., 35, 2297 (1902); 37, 3008, 3011, 3019 (1904); etc. 
 
8 
 
 product is the unsymmetrical form V, which changes to the symmetrical 
 V at higher temperatures, or when treated with sodium ethylate. 
 
 C rCH.CjHeN 
 
 V VI 
 
 In the formation of phthaleins and related types, phthalic anhydride con- 
 denses preferably also to unsymmetrical compounds. 
 
 Finally, although phthalimide itself exists in but one form, to which the 
 symmetrical structure I is usually assigned, substituted phthalimides 
 are known for which the unsymmetrical form IV is preferred. 13 
 
 In the case of succinimide, the condensation with the hydrol was carried 
 out only in alcoholic solution, and a succinyl-leucauramine obtained which 
 was colorless when dry, but gave colored solutions (violet to blue) in alco- 
 hol. Hydrolysis with dil. alkali opened up the imide to the amidic acid, 
 which was further split by dil. acid into succinic acid and leucauramine. 
 
 Oxidized by lead dioxide in acid solution, both phthalyl-leucauramine 
 and the corresponding amidic acid gave carbinols, the -CH grouping 
 changing to -C(OH)-; whereas, with nitrous acid, there resulted a dinitro 
 derivative which probably carries 1 nitro group adjacent to each of the 
 dimethylamino groups. 
 
 4-Nitro-phthalimide did not condense with the hydrol, while 3-amino- 
 phthalimide took up 2 leucauramine residues, 1 on each nitrogen atom. 
 
 Both phthalimidine and phthalide failed to react with the hydrol in 
 alcoholic solution; but when the phthalide and hydrol were fused together, 
 the phthalide exchanged both hydrogens of its methylene group for leuc- 
 auramine radicals, giving a product which probably possesses the struc- 
 
 ture O.CO.C 6 H4.C(CHR 2 )2, and is colored (pink) in acid solution, but 
 is colorless in alkali. The behavior of the phthalimidine was quite un- 
 expected, since it contains the methylene group of phthalide and the 
 imino of phthalimide. 
 
 Saccharin, which differs from phthalimide only in containing an SOi 
 group in place of one of the carbonyl groups of the latter, seems to react 
 with the hydrol only to the extent of salt formation, since the addition of 
 either one to a dil. alcoholic solution of the other gives immediately a 
 deep blue color, and in fact this may be used as a delicate test for the 
 presence of small amounts of saccharin. 
 
 Dehydrothio--toluidine condenses smoothly with 1 mole of the hydrol 
 in alcoholic solution. 
 
 Mohlau and Klopper 14 observed that 2 moles of hydrol united with 1 
 
 13 Hoogewerf and v. Dorp, Rec. trav. chim., 13, 93 (1894). v. d. Meulen, ibid., 15, 
 286, 323 (1896); etc. 
 
 14 Mohlau and Klopper, Ber., 32, 2146 (1899). 
 
of benzoquinone (with elimination of 2 moles of water), whereas with 
 a-naphthoquinone the union occurred with equal moles. In the case of 
 /3-naphthoquinone, and of phenanthraquinone, no condensation took 
 place. They concluded, therefore, that -quinones condense with the 
 hydrol, but 0-quinones do not. Our own experiments do not bear out 
 this conclusion, for we have tried in vain to cause the hydrol to react 
 with anthraquinone in either alcohol or cone, sulfuric acid; nor would 
 alizarin react in the latter solvent at 100, although under similar condi- 
 tions, the hydrol condenses readily with phenols and phenolic ethers; 11 a- 
 and |8-amino-anthraquinones were equally unreactive in alcoholic solution. 
 Mohlau and Heinze 2 state that their attempts to condense the hydrol 
 with acid amides were unsuccessful, except in the case of urea, which united 
 with 2 moles of this secondary alcohol, We have found, further, that 
 negative results are obtained also with thio-urea and with the cyclic ben- 
 zoylene-urea (2,4-dihydroxy-quinazoline) . 
 
 Experimental 
 
 Michler's hydrol was prepared by oxidizing the corresponding bis(-dimethylamino)- 
 diphenylmethane with lead dioxide, as recommended by Mohlau and Heinze; 2 yield of 
 crude product, 85%. To avoid formation of large amounts of tar in the recrystallization 
 of this crude material, it was found advantageous to dissolve about 150 g. in a liter of 
 gasolene previously warmed to 80-85, and then allow the solution to cool. Instead of 
 gasolene, benzene may be employed at the same temperature, but with double the con- 
 centration of hydrol. The melting point of the purified product varied for different lots 
 from 96-98 (uncorr.) . The figures given in the literature run from 96 to 102 . 
 
 Production of the hydrol by the action of sodium amalgam upon an alcoholic solu- 
 tion of the ketone 2 proved unsatisfactory, because of the frequent incompleteness of the 
 reduction and consequent difficulties of purification. 
 
 The lead dioxide employed was precipitated by adding a solution of bleaching 
 powder to one of lead acetate, and was standardized by titration with sodium thiosulfate 
 in presence of a dil. acetic acid solution of potassium iodide. 
 
 Succinyl-leucauramine, ((CH 3 )2N.C 6 H4)sCH.N.CO.CH 2 .CH 2 .CO. A solution of 
 5 g. of succinimide (1 mole) and 13 g. (1 mole) of hydrol in 200 cc. of alcohol was boiled 
 gently for 10 hours. On cooling, a few crystals of the condensation product separated. 
 More were recovered on concentration. Recrystallized from alcohol, the substance was 
 obtained in nearly colorless minute needles, melting at 151 fcorr.), which darkened on 
 standing; yield, approximately 50%. It is soluble also in hot methyl alcohol or hot 
 benzene. 
 
 Analyses. Calc. for C 21 H 25 O 2 N 8 : N, 11.96. Found: 12.09, 12.22. 
 
 Succmyl-dinitro-leucauramine, prepared from the above by the action of nitrous 
 acid, in the same way as the corresponding phthalimide derivative described beyond, 
 crystallized from alcohol as a yellowish-brown powder, melting with decomposition 
 at 94 to 96; yield, about 90%. 
 
 Analyses. Calc. for C 21 H 2S O a N 6 : N, 15.87. Found: 15.61, 15.95. 
 
 p,p '-Bis (dimethylammo)-benzohydryl-succinamidic Acid, ((CH 8 )N.CH<) 2 CH.NH.- 
 CO.CH 2 .CH 2 .COOH. Five g. of succinyl-leucauramine was warmed for 2 hours at 100 
 
 Ger. pats., 58,483, 64,217, 64,306, 66,072, 67,429, 72,898, 76,931, 79,320. 
 
10 
 
 with 10 cc. of a dilute ("about 10%) potassium hydroxide solution, but a clear solution 
 was not obtained. Water (300 cc.) was added, therefore, the mixture boiled, filtered, 
 the filtrate neutralized with dil. acid and worked up as described beyond for the anal- 
 ogous phthalamidic compound. The crude product was crystallized from water contain- 
 ing 10 to 15% of alcohol, and minute colorless needles were obtained. These melted at 
 170, and on standing gradually assumed a pale slaty color. 
 
 Analyses. Calc. for CziH^OsNs: N, 11.39. Found: 11.14, 11.30. 
 
 Phthalyl-leucauramine, ((CHa^N.CeH^CH.N.CO.C^.CO. The requisite phthal- 
 imide was prepared by the method of Dunlap, 18 by fusing a mixture of equimolar 
 amounts of phthalic anhydride and urea, and was obtained in a yield of 97%; m. p., 
 233.5 fcorr.). 
 
 A solution of 10 g. of phthalimide (1 mole) and 18 g. ( 1 mole) of the hydrol, in 300 cc. 
 of alcohol, was boiled gently for 10 hours, and then cooled. Seventeen g. of greenish- 
 yellow leaflets separated from the cold solution, and 4 g. more was recovered by con- 
 centrating the mother liquor, making the total yield 80%. The purified compound 
 melted at 186.7 (corr.), and crystallized in greenish-yellow prisms or leaflets. 
 
 Analyses. Calc. for C^H^N,: C, 75.18; H, 6.27; N, 10.52. Found: C, 74.88, 
 75.30; H, 6.21, 6.36; N, 10.70, 10.70. 
 
 The substance is soluble in cold acetone, difficultly soluble in ether or ligroin, and 
 dissolves in alcohol, ethyl acetate, carbon disulfide, or benzene, at their boiling-points. 
 As phthalimide is difficultly soluble in either carbon disulfide or benzene, it may be 
 separated thus from its hydrol condensation product. When dry hydrogen chloride is 
 passed into an anhydrous ether solution of the new compound, a greenish precipitate 
 separates which is probably the mono-hydrochloride. On further addition of hydrogen 
 chloride, this precipitate loses its color, presumably through formation of the di-hydro- 
 chloride. The latter dissolves in water to form a green solution of the same color as 
 given by the original phthalyl-leucauramine when dissolved in dil. hydrochloric acid. 
 
 When cone, sulfuric acid was substituted for the alcohol in the above reaction and 
 the solution was warmed at 100 for several hours and then cooled, a colorless product 
 separated on neutralization with alkali, which proved to be a labile form of the compound 
 obtained from alcoholic solution. Yield, about 18-20%. It dissolves more readily than 
 the stable form in alcohol, acetone or benzene. After long standing in alcoholic solution, 
 greenish-yellow crystals of the stable form separate. The same change ensues slowly 
 when the dry substance is left in the open; heat accelerates the transformation. When 
 the colorless modification was heated, it melted at about 90, changed to the greenish- 
 yellow form and resolidified. This resolidified product, crystallized from alcohol, 
 showed the correct melting point (186.7) for the stable form. When it was dissolved 
 in cone, sulfuric acid, or even in the dil. acid, a colorless or but faintly colored solution 
 resulted, from which rapid addition of alkali precipitated a colorless oil. This 
 oil congealed to a yellow solid, which gradually assumed the greenish-yellow characteris- 
 tic of the stable form. 
 
 Phthalyl-leucauramine Carbinol, ((CH 3 )2N.C 6 H 4 )2C(OH) .N.CO.C 6 H 4 .CO. Twenty 
 g. of phthalyl-leucauramine was dissolved in a mixture of 160 cc. of water and 12 cc. of 
 cone, hydrochloric acid, and 1 liter of water and 10 cc. of glacial acetic acid were added. 
 The mixture was stirred vigorously while 30 g. of 40% lead dioxide paste, in about 150 
 cc. of water, was added gradually. The stirring was continued for an hour longer, when 
 a solution of 16 g. of sodium sulfate was poured in, to remove the lead. On making 
 the filtrate alkaline, only a small amount of precipitate was formed. The lead sulfate 
 
 16 Dunlap, /. Am. Chem. Soc., 18, 333 (1896). 
 
11, 
 
 precipitate, therefore, was boiled with dil. hydrochloric acid (50 cc. of cone, acid to 300 
 cc. of water), and the mixture filtered hot. As the solution cooled some lead sulfate 
 crystallized and was removed. The filtrate from this was precipitated with dil. 
 sodium hydroxide solution, and the carbinol extracted from this precipitate by hot al- 
 cohol. It was recrystallized from either alcohol or acetone, and dissolved also in chloro- 
 form, but not appreciably in ether. It formed nearly colorless crystals, melting at 176 * 
 (corr.); yield, 60%. 
 
 Analyses. Calc. for C 2 5H 2 5O 3 N 3 : N, 10.11. Found: 10.34, 10.23. 
 
 Dmitro-phthalyl-leucauramine. Five g. of phthalyl-leucauramine was dissolved 
 in 30 cc. of dil. (1:1) hydrochloric acid, and an aqueous solution of sodium nitrite (4 
 moles) run in slowly as long as it caused the separation of precipitate. The nitrite 
 must be added very carefully, so that the temperature does not rise to the point where 
 excessive formation of nitrogen oxides occurs, or the yield of nitro derivative will be 
 diminished. The brown precipitate was collected and crystallized from alcohol, or from 
 glacial acetic acid, and then appeared as a yellowish-brown solid, melting with decompo- 
 sition at 104; yield, 90%. It gave no Liebermann reaction for nitroso groups, and was 
 free from halogen. 
 
 Analyses. Calc. for C 2 6H 23 O6N 6 : N, 14.32. Found: 14.08,14.02. 
 
 An effort to secure the same product was made by dissolving the phthalyl-leucauram- 
 ine in cone, sulfuric acid, adding a mixture of cone, sulfuric and cone, nitric acids at 
 5 to , and finally pouring the mixture into ice water. Some phthalimide separated, 
 but saturation of the nitrate with sodium carbonate precipitated only unchanged initial 
 material. 
 
 Reduction of the dinitro derivative with tin and hydrochloric acid yielded brown 
 oils difficult to handle, which were not further investigated. 
 
 0,0'-Dinitro-/>,'-bis(dimethylamino) diphenylmethane was prepared according to 
 the directions of Pinnow 17 in a yield of 86%; it melted at 188 (uncorr.); Pinnow gives 
 191.5. Twenty g. of this product was suspended in 600 cc. of water and sufficient 
 hydrochloric acid added to give a clear solution. Twenty-six g. of lead dioxide paste 
 (40%), mixed with 100 cc. of water, was stirred in and the oxidation continued for an 
 hour at laboratory temperature; the mixture was then heated to 60 to complete the 
 reaction, and on dilution with water, the original diphenylmethane compound separated 
 unaltered. In view of this result, it seemed profitless to attempt the oxidation of 
 the dinitro-phthalyl-leucauramine. 
 
 ^,/?'-Bis(dimethylamino)-benzohydryl-phthalamidicAcid, ((CH 3 ) 2 N.CH4)jCH.NH.- 
 CO.C 6 H 4 .COOH. Fifty g. (1 mole) of phthalyl-leucauramine was covered with 50 cc. of 
 a dil. (about 10%) aqueous potassium hydroxide solution (slightly over 1 mole), and 
 the mixture heated at 100 for about half an hour, at the end of which time the solid was 
 nearly all dissolved. Longer heating caused evolution of ammonia, due probably to 
 the separation of leucauramine and the hydrolysis of the latter to hydrol and ammonia. 
 Water was added to the alkaline solution and then dil. sulfuric acid to neutralization. As 
 the precipitate formed was soluble either in acid or alkali, it was found advisable not 
 to overrun the neutral point. This point was easily detected by the sudden change in 
 color. The colorless precipitate dissolved readily in methyl or ethyl alcohol, chloro- 
 form or acetone, but proved very difficultly soluble in carbon tetrachloride or gasolene. 
 On recrystallization from alcohol, colorless needles were obtained, which melted with 
 decomposition at 163.8 (corr.); yield, 90%. 
 
 Analyses. Calc. for C K H 27 O^ 3 : N, 10.07. Found: 10.03,10.14. 
 
 Some of this amidic acid was dissolved in dil. hydrochloric acid and the solution 
 
 Pinnow, Ber., 27, 3161 (1894). 
 
12 
 
 heated at 100 for an hour. The solution was then diluted and cooled. Phthalic acid 
 separated and was filtered out. The filtrate was then made alkaline and leucauramine 
 precipitated. Similar results were secured when the original phthalyl-leucauramine was 
 saponified with dil. (20%) hydrochloric acid at 100, without separation of the inter- 
 mediate amidic acid. 
 
 Oxidation of the Amidic Acid. Five g. (1 mole) of the amidic acid was dissolved 
 in 40 cc. of water and 3 cc. of cone, hydrochloric acid, and a solution of 5 cc. of glacial 
 acetic acid in 200 cc. of water poured in. This solution was stirred vigorously while 
 6 g. (1 mole) of lead dioxide paste (40%), suspended in 50 cc. of water, was added slowly. 
 The stirring was continued for half an hour longer, and the lead then precipitated by 
 dil. sulfuric acid. The lead sulfate was removed and washed with dil. hydrochloric acid, 
 the washings being combined with the original filtrate. The united filtrate and washings 
 were made alkaline, and the desired carbinol thereby precipitated. It was purified by 
 crystallization from dil. acetone, and then formed a brownish solid, melting at 187 
 (corr.), and soluble also in alcohol; yield, 75%. 
 
 Analyses. Calc. for ((CH,),N.CH 4 )2C(OH).NH.CO.C 6 H4.COOH: N, 9.70. 
 Found: 9.48, 9.75. 
 
 Michler's Hydrol and Phthalimidine. The phthalimidine was prepared from 
 phthalimide in the usual way, 18 and melted at 150 (uncorr.). Five g. (1 mole) of this 
 imidine and 30.5 g. (3 moles) of the hydrol were heated with 250 cc. of alcohol and a 
 few drops of glacial acetic acid for a day at 100, but no condensation occurred and the 
 initial materials were recovered unchanged. 
 
 Di-bis(dunethylammo)-benzohydryl-phthalide, 
 Phthalide and the hydrol were mixed in the proportion of one mole of the former to two 
 of the latter, a few drops of glacial acetic added, and the mixture was heated at 100 for 
 6 to 8 hours, giving a blue, pasty mass which solidified on cooling. This solid was pul- 
 verized and extracted with boiling alcohol, to recover unchanged phthalide and hydrol. 
 The insoluble residue was crystallized from a mixture of 1 part of gasolene and 2 
 parts of xylene, and then formed reddish-brown prismatic crystals, melting at 201 
 (corr.), which were but slightly soluble in alcohol, ethyl acetate, acetone, carbon tetra- 
 chloride, benzene, aniline or gasolene, and somewhat more soluble in hot xylene; yield, 
 about 10%. The same compound resulted when the phthalide and hydrol were present 
 in equimolar proportions, and no monobenzohydryl derivative was encountered. 
 
 Analyses. Calc. for C^HUeO^: C, 78.99; H, 7.30; N, 8.77. Found: C, 78.84, 
 78.63; H, 7.32, 7.20; N, 8.79, 8.85. 
 
 With acids, the compound turns pink; but the color is discharged on addition of 
 alkali, and the freshly separated compound is practically colorless. In alcoholic solution, 
 the phthalide and hydrol do not interact at the boiling point of the mixture. The 
 phthalide used in these experiments was prepared by hydrolysis of nitroso-phthalimi- 
 dine, 18 and melted at 73 (corr.). 
 
 Michler's Hydrol and 4-Nitro-phthalimide. Equimolar amounts of the two were 
 dissolved in alcohol and the solution boiled for 10 hours on a steam-bath. The solution 
 turned blue, but the hydrol and imide were recovered from the solution unaltered. 
 
 3-Leucauraminyl-phthalyl-leucauramine, ( (CHs^N.QH^CH.NH.CeHgfCO^N.- 
 CH(C 6 H4.N(CH 3 )2)2. 0.87 g. (1 mole) of 3-amino-phthalimide and 3 g. (2 moles) 
 of hydrol were dissolved in 35 cc. of alcohol containing a few drops of glacial acetic 
 acid, and the solution boiled gently for 10 hours. As the mixture cooled, a small 
 amount of tar separated, and more began to come out on further concentration. The 
 
 18 Graebe. Ann., 247, 291 (1888); Ber., 17, 2598 (1884). 
 
13. 
 
 alcoholic solution, therefore, was treated with dil. hydrochloric acid, and the clear sol- 
 ution precipitated by neutralization with alkali. The dried precipitate amounted to 
 3 g. Boiling with alcohol appeared to decompose it slowly with formation of tar, as 
 noted above, but crystallization from acetone yielded greenish-yellow plates, melting 
 at 219-220 (corr.), analysis of which showed that both the amino and the imide groups 
 had reacted with the hydrol. 
 
 Analyses. Calc. for C^H^CWe: C, 75.78; H, 6.77. Found: C, 75.61, 76.09; 
 H, 7.05, 7.11. 
 
 The product is difficultly soluble in petroleum ether, but rather readily soluble in 
 benzene, and a mixture of the two may be used as a crystallizing medium, but is not so 
 satisfactory as acetone. Its solutions are not fluorescent, although those of the initial 
 amino-phthalimide are. The pale color of the solid substance is also noteworthy, and 
 is in harmony with its leucauramine structure. 
 
 Michler's Hydrol and Saccharin yielded no condensation product when the two 
 were heated together in equimolar proportion in alcoholic solution, with or without 
 the addition of small amounts of glacial acetic acid. It was observed, however, that 
 when the two substances were brought together even in very dilute alcoholic solution, 
 a deep blue color resulted, presumably due to the formation of a quinoid salt of the hy- 
 drol, and this reaction appears to be a delicate test for either compound. The color is 
 discharged by sulfur dioxide and restored by addition of the component originally present 
 in the smaller amount. The corresponding ketone (Michler's ketone) and hydrocarbon 
 give no such color reaction when saccharin is added to their alcoholic solutions. 
 
 Michler's Hydrol and Anthraquinone. No condensation was effected either in 
 alcoholic solution or in cone, sulfuric acid. 
 
 Michler's Hydrol and Alizarin. In cone, sulfuric acid solution, no condensation 
 occurred. 
 
 Michler's Hydrol and Amino-anthraquinones. The condensation was attempted 
 in alcoholic solution, with both a- and /3-amino-anthraquinone, and failed in both 
 cases. 
 
 Michler's Hydrol and Thio-urea. Mohlau and Heinze,* report that the hydrol 
 condenses in alcoholic solution with urea, but our experiments with thio-urea were 
 less successful. We dissolved 2 moles of the hydrol and 1 mole of thio-urea in alcohol, 
 and boiled the solution gently for 8 hours. There was no indication of any change, so 
 more thio-urea (3 moles) was added and the boiling resumed, but we failed to accomplish 
 any condensation. 
 
 Michler's Hydrol and Benzoylene-urea did not condense in alcoholic solution. 
 
 / S 
 p,p'-Bis (dimethylamino) -benzohydryl-dehydrothio-^-toluidine, CH 3 . CHjj<^ 
 
 C 6 H4.NH.CH(C 6 H4.N(CHs) 2 )2. Five g. (1 mole) of dehydrothio--toluidine and 5.5 
 g. (1 mole) of the hydrol were dissolved in 250 cc. of alcohol and the solution was boiled 
 gently on the steam-bath. The original blue color of the solution was almost completely 
 discharged after a half hour's boiling and a faint fluorescence appeared, while a straw- 
 yellow precipitate separated from the hot solution, the amount increasing as the boiling 
 was continued. When this precipitate no longer increased in amount, the solution was 
 cooled and filtered, and a further crop of crystals recovered by concentration of the 
 mother liquor. The crude product was purified by crystallization from benzene, washed 
 with acetone, to remove any adhering dehydrothio-/>-toluidine, and then appeared as a 
 pale yellow micro-crystalline solid, melting at 190-191 (corr.), moderately soluble in 
 alcohol or in benzene, and difficultly soluble in acetone or ether; yield, 75%. 
 
 Analyses. Calc. for C M H M N 4 S: C, 75.60; H, 6.50. Found: C, 75.94 ; H, 6.55. 
 
14 
 
 Summary 
 
 1. ,'-Bis(dimethylamino)-benzohydrol, better known as Michler's 
 hydrol, condenses with the imides of succinic and phthalic acids to suc- 
 cinyl- and phthalyl-leucauramines, which can be hydrolyzed by alkali to 
 the corresponding amidic acids. The results of the condensation were 
 the same whether carried out in cone, sulfuric acid or in alcoholic solution. 
 
 2. Phthalyl-leucauramine exists in a labile, colorless (m. p. 90), and 
 a stable, greenish-yellow, modification (m. p. 186.7), which are inter- 
 convertible. 
 
 3. These acyl leucauramines yield the corresponding carbinols when 
 oxidized by lead dioxide, or give dinitro derivatives when treated with 
 nitrous acid. 
 
 4. Phthalimidine and the hydrol do not condense in alcoholic solution. 
 
 5. Phthalide reacts with two moles of the hydrol. 
 
 6. 3-Amino-phthalimide also condenses with 2 moles of hydrol, one 
 entering the amino and the other the imide group. 4-Nitro-phthalimide, 
 on the other hand, does not react. 
 
 7. The hydrol is a delicate reagent for detecting saccharin in alcoholic 
 solution, giving a deep blue coloration even in dilute solutions. 
 
 8. Dehydrothio-^-toluidine condenses readily with the hydrol in alco- 
 holic solution. 
 
 9. Anthraquinone, its a- or 0-amino derivative, alizarin, thio-urea or 
 benzoylene-urea, fails to react with the hydrol, under the conditions of 
 our experiments. 
 
BIBLIOGRAPHY OF MICHLER'S HYDROL 
 1876 Michler-Dupertuis, Ber., 9, 1899; Ann., 184, 174. 
 1883 Kern, D. R. P. 27,032; FrdL, [1] 76. 
 1884 Badische, Ber., 17R, 244. 
 1887 Myer, Ber., 20, 1733. 
 
 1889 Nathansohn-Miller, Ber., 22, 1879; D. R. P. 54,113. 
 1890 Bayer, D. R. P. 58,483, 67,429, 58,969, 60,606; Badische, D. R. P. 58,198, 58,277- 
 
 Einhorn, D. R. P. 69, 554. 
 1891 Nolting, Ber., 24, 553, 3127, 3136, 3139; Bayer, Ber., 24R, 873, 926; Bayer, 
 
 D. R. P. 66,072, 63,743, 64,306, 68,291, 69,654, 66,712; Badische, D. R. P. 64,217. 
 1892 Bayer, Ber., 25R, 356, 836, 885; Bayer, D. R. P. 67,434, 69,948, 72,898, 68,865, 
 
 67,232, 68,381, 73,112, 76,073, 80,510. 
 1893 Bayer, Ber., 26R, 259, 464, 562, 563, 631, 632, 633, 916, 920; Bayer, D. R. P. 
 
 80,669, 80,282; Einhorn, Ber., 26R, 849; Rosenthiel, Bull. [3] 9, 127; Weil, 
 
 D. R. P. 75,334; Badische, D. R. P. 70,908, 76,931 ;Add., 5534, 5540. 
 1894 Weil, Ber., 27, 1408, 3316, R825; Bayer, Ber., 27R, 355, 912; Bayer, D. R. P. 
 
 81,374, 79,250, 82,268, 82,270, 82,634, 80,510/90,881, 82,570; Badische, D. R. P. 
 
 79,320; Badische, Ber., 27R, 960; Geigy, D. R. P. 80,982; Rosenthiel, Bull, 
 
 [3] 11, 405. 
 1895 Bayer, Ber., 28R, 585, 705, 880; Geigy, D. R. P. 87,176; Badisch? D. R. P. 
 
 85,199; Rosenthiel, Bull, [3] 13, 275. 
 1896 Fritsch, Ber., 29, 2300; Badische, Ber., 29R, 317; Geigy, Geigy, Ber., 29R, 715; 
 
 Bayer, D. R. P. 90,881; 97,106; Bayer, Ber., 29R, 705; Meister-Lucius-Bruning, 
 
 D. R. P. 96,230. 
 1897 Hinsbeig, Ber., 30, 2803; Suais, Bull, [3] 17, 517; Bayer, D. R. P. 97,286, 98,546; 
 
 Meister-Lucius-Bruning, D. R. P. 97,638; 97,822; 98,012. 
 1898 Klager-Allensdorff, Ber., 31, 1002; Mohlau, Ber., 31, 2351; Vidal-Haas, D. R. P. 
 
 106,721, 116,352, 116,566; Lucius-Bruning, D. R. P. 108,129, 110,086. 
 1899 Mohlau-Klopfer, Ber., 32, 2146; Aktien-Gesellschaft, D. R. P. 109,664, 112,175; 
 
 Add., 6450; Lucius-Bruning, D. R. P. 111,506 
 1900 Hantzsch-Osswald, Ber., 33, 283; Mohlau-Schaposchnikoff, Ber., 33, 799; Mohlau- 
 
 Kegel, Ber., 33, 2860; Bayer, D. R. P. 125,580. 
 1901 Mohlau-Heinze, Ber., 34, 882; Escherich-Moest, D. R. P. 133,896; Add., 8316, 
 
 7664; Leonhardt, D. R. P. 12,806; Mohlau-Gralert, Ber., 34, 3384. 
 1902 Mohlau-Heinze, Ber., 35, 359, 376; Casein, D. R. P. 149,322, 148,031, 144,536; 
 
 Fischer- Weiss, Centralblatt, [1] 471; Guyot-Granderye, Centralblatt, [1] 873; 
 
 Elbs-Brand, Centralblatt, [2] 1199. 
 
 1903 Ehrlich-Sachs, Ber., 36, 4298; Fritsch, Centralblatt, [2] 1440. 
 1904 Nolting, Ber., 37, 1908; Lucius-Bruning, D. R. P. 166,308; 167,348, 168,080; 
 
 Merck, D. R. P. 167,462, 167,463. 
 1905 Aktien-Gesellschaft, D. R. P. 171,684; Reitzenstein-Runge, Centralblatt, [1] 
 
 1020. 
 1906 Nolting-Gerlinger, Ber., 39, 2053; Reitzenstein-Rotschild, Centralblatt, [1] 1168; 
 
 Fosse, Bull, [3] 35, 1005. 
 1907 Reitzenstein-Schwerdt, Centralblatt, [2] 1413; Badische, D. R. P. 186,889; 
 
 Volocek-Jelinek, Ber., 40, 408; Fosse, Centralblatt, [1] 1696; Geigy, Centralblatt, 
 
 [1] 776; Bayer, Centralblatt, [2] 988. 
 1908 Fosse, Chem. Abstr., 823, 2387, 2689; Mohlau, Ber., 41, 989; Auwers-Eisenchlor, 
 
 Centralblatt, [1] 1048; Bielki-Koloniew, Centralblatt, [2] 877; Gyot-Pignet, 
 
 Centralblatt, [2] 51. 
 1909 Fosse, Ann. Chim. Phys., [8] 18, 400, 503, 531; Votocek-Kranz, Ber., 42, 1602. 
 
1910 Sudborogh-Beard, Chem. Abstr., 2116; Fosse, Bull., [4] 7, 229; Compt. rend., 
 
 150, 179; Reitzenstein-Breuning, Ann., 372, 263; Marschalek-Nicolajewsky, 
 
 Ber., 43, 1701. 
 1912 Villiger-Kopetschni, Ber., 45, 2910; Reitzenstein-Bonitsch, J. Prak. Chem., 
 
 [2] 86, 38, 61, 66; Brit. P. 3134; Schmidlein-Lang, Ber., 45, 908; D. R. P. 250,366; 
 
 Chem. Abstr., 3531; Kyot-Kovache, Compt. rend., 155, 838. 
 1913 Gyot-Kovache, Compt. rend., 156, 1326; Centralblatt, [2] 45; Straus-Zeime, Ber., 
 
 46, 2269; Votocek-Kohler, Ber., 46, 1763; Braun-Koscielski, Ber., 46, 1528; 
 
 Green, J. C. S., 103, 927; Fischl, Monats., 34, 337, 342 note. 
 1914 Esseln-Clarke, Centralblatt, [1] 1277. 
 
 1917 Montagne, Chem. Weekblad, 13, 1246, 1966; Ber., 49, 2243; Chem. Abst., 586. 
 1918 Kovoche, Ann. Chim. Phys., [9] 10, 184. 
 
 1919 Kovache, Rev. Gen. de materies colorantes, etc., 23, 25; Centralblatt, [1] 1022. 
 1920 Fosse, Ann. Chim. Phys., [9] 13, 118, 154; Chem. Abstr., 1963. 
 1921 Fosse, Chem. Abstr., 1711. 
 
VITA 
 
 Aaron Ruderman was born May 21, 1895. After a preliminary educa- 
 tion in the schools of New York City he entered the College of the City 
 of New York in 1915. In May 1918 he entered the Chemical Warfare 
 Service, U. S. A. and was assigned to U. S. Bureau of Standards. After 
 his discharge from the army he was awarded the degree of B.S. in Feb. 
 1919. Since then he pursued graduate studies at Columbia University 
 under the faculty of pure science. He received the degree of M.A. in 1920. 
 
Photomount 
 Pamphlet 
 
 Binder 
 Gaylord Bros. 
 
 Makers 
 Syracuse, N. Y. 
 
 PAT. JAN 21, 1908 
 
 5020 
 
 A 4 
 
 UNIVERSITY OF CALIFORNIA LIBRARY