THE PREPARATION OF GLYCOLS 
 
 BY 
 
 ALBERT LEWIS TANENBAUM 
 
 THESIS 
 
 FOR THE 
 
 DEGREE OF BACHELOR OF SCIENCE 
 
 IN 
 
 CHEMICAL ENGINEERING 
 
 COLLEGE OF LIBERAL ARTS AND SCIENCES 
 
 UNIVERSITY OF ILLINOIS 
 
 1922 
 

 \"J (AsU* 
 
 UNIVERSITY OF ILLINOIS 
 
 t r , T t 04 If'';'' 
 
 192 
 
 THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY 
 
 Albert Lewis T an e nbaurr. 
 
 ENTITLED T 
 
 ratie*'* 0 t nivoc^ s 
 
 IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE 
 degree of ? chjslor of_ _ B_cience _ _i n Ch_e rn i 2 I 
 
 (2-CaaJL. _ : 
 
 Instructor in Charge 
 
 Approved : 
 
 HEAD OF DEPARTMENT OF 
 
 500260 
 
Digitized by the Internet Archive 
 in 2015 
 
 https://archive.org/details/preparationofglyOOtane 
 
THE PKBPaHAI 1 I OB GY GLYCOLS 
 
I wish to extend mp - sincere thanks and 
 appreciation to Dr. C* o* Llarvel, under 
 whose supervision this work was done, 
 for helpful suggestions and interest 
 shown during the experimental work* 
 
Pable of Contents 
 
 Page 
 
 Introduction 1 
 
 theoretical £ 
 
 Experimental 
 
 Phenoxy propyl magnesium bromide 5 
 
 ^‘-ch.lorpropionic acid 6 
 
 phenoxy propyl cyanide 6 
 
 Ethyl t«*phenoxy butyrate 7 
 
 Phenoxy butyl alcohol 9 
 
 % -Phenoxy butyl b-nitrobenzoate 11 
 
 Phenoxy butyl bromide 12 
 
 fetrame thylene bromide 12 
 
 Summary 14 
 
 Bibliography 15 
 
Introduction 
 
 This work was undertaken with, the purpose of synthesizing 
 phenoxy butyl bromide and tetramethylene bromide by a method 
 that would make use of comparatively cheap and readily access- 
 ible materials* 
 
 Ethylene bromide, trimethylene bromide, and pentamethylene 
 bromide can be obtained at a reasonable cost. The preparation 
 of tetramethylene bromide would fill the gap in this series of 
 valuable reagents, ^leo, it was wanted in this laboratory as 
 an intermediate in the preparation of anaesthetics. 
 
 Phenoxy ethyl and phenoxy propyl bromides can be prepared 
 in good yields from sodium phenolate and ethylene and trimethyl- 
 ene bromides, respectively. Phenoxy butyl bromide held a 
 special interest, at this time, since it was to be used in the 
 preparation of derivatives of lysine. 
 
2 
 
 Theoretical and historical 
 
 Tetramethylene "bromide was first prepared "by Guetavson and 
 Dem^anoff • by recluotic " ethylene cyanide to tetr amethylene 
 diamine, and subsequent treatment with silver nitrite to form 
 tetramethylene glycol, which was split with hydro bromic acid* 
 
 The yield was exceptionally low* 
 
 Hammonet^ prepared it by electrolyzing the potassium salt 
 of ^-amyloxypropionic acid# The 1,4 diamyloxybutane formed was 
 split by means of hydrobromic acid. 
 
 J. V. Braun and BeschheS synthesized tetramethylene bromide 
 by means of the following series of reactions: 
 
 These methods of preparation, may be used when only small 
 -.mounts of the product are desired, but a cheaper method would 
 allow the use of it in larger amounts. 
 
 Since phenoxy propyl bromide is a comparatively cheap re- 
 agent now, it was decided to prepare the Grignard reagent of 
 this compound and treat it with formaldehyde, which should form 
 phenoxy butyl alcohol. This could be converted into the mono and 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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dibromo compounds. -a mixture of products wes formed, from which 
 phenoxy "butyl alcohol could not be isolated* 
 
 attempt was then made to prepare the product desired by 
 treating the Grignard reagent with mono -chi or-methyl ether, a 
 modification of a method used by hammonet, but it was found thft 
 in this case also, the product obtained was a mixture of many 
 compounds. 
 
 Both the results obtained, and the fact that an equivalent 
 amount of magnesium vxmld not react with the halide, suggested 
 the i ossibility that the Grignard reagent was only forming to a 
 limited extent, To prove this contention, the Grignard reagent 
 v/as treated with water. The amount of phenyl propyl ether formed 
 would be an indication of the amount of Grignard reagent formed. 
 a compound, boiling at 185-186°, was isolated from the reaction 
 mixture. The yield was about 20^ theory. Since the phenoxy 
 propyl magnesium bromide formed only to such a slight extent, it 
 was decided to drop this method for the preparation of the 
 desired products. 
 
 It was decided to prepare phenoxy propionic acid, which 
 should form, by the electrolysis of its potassium salt, 1,4 &i- 
 phenoxy butane. This acid could be prepared much more cheaply 
 than the one used by hammonet and might give better yields. 
 
 Trimethylene chlorhydrin has recently become available for 
 use, through its preparation from trimethylene glycol. The 
 oxidation product of tmis compound, fc-chlor propionic acid, 
 
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- 4 - 
 
 oould be treated with. 30dium phenolate to give the phenoxy 
 propionic acid. ^lso, since B-ohlorpropionio acid is 
 valuable reagent, the department was interested in developing 
 the proceedure for this preparation* iiuns were made under 
 various conditions, but the best procedure was not determined, 
 since this method of preparing tetramethylene bromide and phenoxy 
 butyl bromide was dropped in favor of the method, described be- 
 low, which seemed to have greater possibilities® 
 
 The starting point for this method was phenoxy propyl 
 bromide. It had been converted, in our laboratory, into phenoxy 
 propyl cyanide in 72$ yields. Phis yield was increased to 95- 
 95$. The cyanide was than converted into e thy 1-S -phenoxy 
 butyrate, in 80$ yields, which was reduced to the corresponding 
 alcohol by a modification of the method of levene and Allens 
 The time of reduction was reduced to fifteen minutes, the total 
 time needed for the reduction of 100 g* of the ester being about 
 five hours. Of this, three hours was t alien up in allowing the &1« 
 cohol and toluene to distill from the reaction mixture, file 
 yield was 62-*68$ theory* The phenoxy butyl alcohol was then 
 treated with phosphorous tribromide in order to prepare phenoxy 
 butyl bromide. Treatment of the alcohol with 48$ hydro bromic 
 acid gave a mixture of tetramethylene bromide and phenoxy butyl 
 bromide. The desired products can be prepared by this method in 
 fc.ir yields and at a reasonable cost® 
 
PliEUGXY PflOPYL llaGuBSIUk BBOLilDE 
 
 In a 1 1. round-tot tom flask, fitted with an upright con- 
 denser 300 c.c. of dry ether, 11.5 g. of magnesium and a crystal 
 of iodine were placed* 100 g. of phenoxy propyl bromide were 
 tnen added over a period of one hour. The reaction seemed to 
 run smoothly except that only about one half of the magnesium 
 reacted, and some magnesium bromide separated out. 
 
 an equivalent amount of trioxymethylene was added to the 
 drignard reagent, and the mixture heated on the steam bath for 
 three hours. Water and enough hydrochloric acid to dissolve the 
 precipitated solids were added and the ether l^yer separated, 
 ^fter distilling the ether the residue was distilled under di- 
 minished pressure. It boiled from 95° to 170° under twenty 
 vnm. pressure, no clear cut fractions being obtained* 
 
 To another run of the Grignard reagent an equivalent amount 
 of monochlor methyl ether 7/as added, The reaction mixture was 
 treated in the same manner as described above, but the product 
 could not be separated into definite fractions. 
 
 To still another run of the Grignard reagent water was 
 added, and the product obtained distilled very carefully. Small 
 fractions of unsaturated compounds and a phenol were obtained. 
 The highest boiling fraction turned solid on cooling. It was 
 assumed to be diphenoxy hexane. The largest fraction boiled at 
 
 185-185° at atmospheric pressure. Its specific gravity was 
 

 
 * 
 
 4 
 
 
 
- 6 - 
 
 .941$£° and index of refraction 1*5012 at 25°. It was assumed 
 4 U 
 
 to be phenyl propyl ether, which toils at 183*9° and has a 
 specific gravity of .9459 ^^ * f he yield was 12 g* (20^j) theory* 
 
 IhLUR PhOPIOxv'IG aGXD 
 
 In a 31. round -hot tom flask fitted with a mechanical 
 stirrer, upright condenser and dropping funnel were placed 350 
 g. of fuming nitric acid. 120 g. of trimat hylene chlorhydrin 
 were added slowly through the dropping funnel ( about two hours). 
 When the temperature of the reaction mixture rose to about 35° 
 (in ten-. en minutes* ), An ice bath( about 5-10°) was placed 
 around the flask* After the addition of the chlorhydrin, the 
 reaction mixture was stirred for three hours. It was then 
 allowed to stand at room temperature overnight. Water (300 c.c.) 
 was added to the mixture and the &.chlorpropionic acid extracted 
 with ether, The acid was distilled under diminished pressure. 
 
 76 grams(55fj) of the acid were obtained. P.P. 106-107 at eeven- 
 mm. ; 112-114 at twenty~tw( *nw. ; 115-116 at twenty- 
 sJb The acid solidified on cooling (h. I. 41°). 
 
 The reaction will not take place in a freezing mixture® 
 at room temperature the reaction is so vigorous that the 
 contents of the flask are lost through, the condenser tube. 
 
 PiiMOXY PhGPYL C Yah IDE 5 
 C » 0 » ( GE , ) (B ■+.. CH 1 ^ \ ) w* + 
 

- 7 - 
 
 In a 5 1* round-tot tom flask fitted witli a reflux condenser, 
 1000 g. of phenoxy propyl bromide, 325 g* of sodium cyanide, 325 
 g # of water, and 500 g. of ethyl alcohol( 95fj) were placed. Che 
 flask was heated on a steam bath for from fifteen to twenty hours. 
 Che heat was so regulated that the reaction mixture refluxed 
 rather rapidly. Che flask v/as then cooled and about 800 cc. of 
 ether added. Che ether layer, containing the small amount of 
 unchanged phenoxy propyl bromide and the cyanide, was decanted. 
 
 Che water layer was then extracted with about 100 c.c. of ether, 
 which was added to the first ether portion. Che ether was dis- 
 tilled on a steam bath{ to a volume of about 800-900 c.c.) and 
 the residue decanted from the small amount of inorganic salt 
 that separated out. Che residue v/as distilled under diminished 
 pressure. ^ small amount of the bromide passed over at about 
 148° at 23 mm. (159° at 34 ram*). Che water-white phenoxy propyl 
 cyanide then distilled over. (B*P. 162-166 at £2 mm.; 172-175 at 3f 
 mm.) 695-711 g. of phenoxy propyl cyanide were obtained( 93-95'^ 
 t he ory ) • 
 
 It is not advisable to reflux for a shorter tine if maximum 
 yield is desired. 
 
 JCCAa h'uCYxu.Ch 
 
 EOgH-.G* ( CHg) 3U+2C - + SC *2H C — ^CgH^QfOH ) 3 C00C g H 5 
 
 (ITH ) 30 
 4 2 4 
 
\ l 
 
 
In a 5-1 round-bottom flask, fitted with en efficient 
 reflux condenser , were placed 625 g. of 95^ alcohol, 509 c.e* 
 of cone* sulfuric acid( ap* gr . 1.84)and S00 g« phenoxy 
 cyanide. She mixture was then heated and kept refluxing for 
 seven hours* The flask was then cooled, which caused, the 
 ammonium sulfate to separate out and the ester to come to the 
 top. The liquid contents were poured into a separatory funnel 
 and the water layer drawn off into the flask containing the 
 ammonium sulfate. The ester layer was washed with a dilute 
 sodium carbonate solution to remove small amounts of phenoxy 
 butyric acid that might have been present. Enough water was 
 added to dissolve the ammonium sulfate, and this was extracted 
 with ether, which was washed with a dilute sodium carbonate 
 solution said then added to the ester. The ester was distilled 
 under diminished pressure. Yield 510-516 g.( 79-80^ theory). 
 
 B. P. 160-168° at 25 mm., 168-174° at 27 mm., 178-184° at 40 mm. 
 Index of refraction 1.498 at 27°. 
 
 Analysis; wt, of sample .4410 grams 
 
 Obtained 861*6 c.c. of GG& at 52.0° an< * Va].: an. 
 
 Q. pound 68.95 Calc* 69.19 
 
 jx white curdy solid sometimes separated out during the 
 distillation, but this had no effect upon the yield or purity 
 of the product. It seems as if more of this solid would separ- 
 ate out if the reaction mixture was thrown into water and ex- 
 
 tracted with ether* 
 
-9 
 
 I" l -rt i * S /CY EUlfiTZi xijjOuxiOX 
 
 Xc,xxc • w • ( GHp ) rrOOOOpxxir__iX± — ■ — y O5K5 • 0 • ( Xxxc> ) ^CxIgOh. 
 D J fv u C 1 _ H — Un 
 
 2he apparatus consisted of 
 a 5-1. round-bottom flask fitted 
 with a rubber stopper, holding a 
 mechanical stirrer, 3/4 inch 
 tube, and separatory funnel, fhe 
 tube was bent just outside of the 
 stopper at an angle correspond- 
 ing to that at which the con- 
 denser was to be set (about 45°). 
 
 I he tube was connected to a sin 
 foot condenser ( by means of a rubber connection) having a con- 
 denser tube 5/4 inch in diameter, phis proved oo j 3 a T ^ry 
 efficient arrangement as the liquid -lowed back on one side 
 of the tube while the vapors flowed up the other side. 
 
 110 grams of sodium and 200 c.c. of dry toluene were 
 "olaced in the flask and heateci in an oil batu un>jil tne oOdium 
 was melted. Jhe stirrer was then rotated vigorously and as 
 soon as the sodium was in a finely divided state, the oil 
 bath was removed. <Yhile the flask was cooling, the stirrer 
 was run continuously. 2he sodium solidified into small solid 
 particles which were kept mijwed with the toluene by means of 
 
- 10 - 
 
 tlie stirrer. An ice bath was then placed around the flask* a 
 uinf'.ro of 100 g. of ethyl S-phenoxy butyrate and 100 c.c. of 
 absolute alcohol were added. This might have been added as 
 rapidly as the condenser was capable of condensing the alcohol 
 vapor(from 2 to 2 1/2 min.), fhe ice bath was txen removed, 
 otherwise the sodium ethylate would form solid cakes* 500 c.c. 
 of absolute alcohol wsre then run in at such a rate that the 
 contents of the flask remained mushy, fhe total time consumed 
 up to this point was about 15-20 min. 3y this time most of 
 the sodium would have been consumed, but the reaction was 
 allowed to proceed for 15 minutes longer# 
 
 I 
 
 About 300 c.c. of water were then added(in about 5 min.) 
 until everything was in solution, fhe oil bath was replaced 
 and the mixture refluxed for 30 minutes in order to saponify 
 any small amount of unconverted ester that might have remained. 
 
 ^fter refluxing, the flask v7as connected by a fraction- 
 ating tube to a condenser set for downward distillation, and 
 the alcohol and toluene distilled completely from a steam bath. 
 Enough water was added to dissolve the solid that separated 
 out, and the solution was extracted twice with ether, fhe 
 ether layers ?/ere washed with water, combined, and the ether 
 distilled, fhe residue was distilled under diminished pressure, 
 fne forerun, con Lng of a little e . , water, and toluene, 
 was discarded. Yield of phenoxy butyl alcohol, 50-54 grams 
 ( 62-68/ theory). B.p* 162-154° at 19 mm., 166-1680 at 24 m. 
 
- 11 - 
 
 Index of refraction 1*520 at 27°. 
 
 Analysis: Wt. of sample .4470 grams 
 
 Obtained 751*0 of GO at 32.5° and 738*5 ram* 
 
 G. ffound 72.22 Calc. 72.24 
 
 Ale ohol( which had been distilled over lime) was distilled 
 over enough, sodium to take up the remaining water* 
 loluene was dried over sodium. 
 
 fhe ester was kept over anhydrous sodium sulfate, 
 fhe closer the stirrer to the bottom of the flask, the 
 greater the subdivision of the sodium* 
 
 ah ice bath should at all times be handy during the re- 
 duction. If the reaction becomes too vigorous and the alcohol 
 shoots up into the condenser, stopping the stirrer and placing 
 an ice bath around the flask will usually stop this action. 
 
 Good yields can be obtained only when the apparatus and 
 materials are absolutely dry. 
 
 Occasionally yields as high as 75;] have been obtained. 
 Other methods cf extraction have been tried but the 
 method described is easiest of operation and gives the best 
 yields. 
 
 S-MMOXY [ ^UIESOBE^S 0 A 
 
 10 gi of k-nitro benzo 2 rl chloride and phenoxy butyl 
 alcohol in slight excess were placed in an Brlenmeyer flask 
 and heated on a steam bath for one hour, a light yellow solid 
 
“IE- 
 
 formed wlii oh was recrystallized twice from 95$ alcohol, li. p. 
 90°. 
 
 Analysis: $ C. Bound 64. El. Gale. 64.73 
 
 $ Hg found 5,34. Calc. 5.43 
 
 PxAAGXY BUTYL BBGLIDE 
 
 In a 150 o.c. Erlenneyer flask 52 g. of phenoxy butyl 
 alcohol were placed. 33 g. of phosphorous tribromide were 
 then added in small amounts. She flask was cooled by means 
 of an ice bath. It was allowed to stand for 24 hours and then 
 heated on a steam bath for 15 minutes, The reaction mixture 
 was poured into water, agitated, and the oily layer separated. 
 It was distilled under diminished pressure. 50 grams(70$ 
 theory) of phenoxy butyl bromide were obtained(B. P. 155-158° 
 at 24 mm. ) , The product solidified on cooling. M* P. 40 0 „ 
 
 Analysis: Wt. of sample .5811 grams 
 
 26.44 c.c, of .08513 IT.AgllO^ used 
 
 $ Br 2 Pound 34.54. Gale. 34.89 
 T A T.uu.lA T A YLAB A BHOMBDL 
 
 In a 500 c.c. ground -glass stoppered flask fitted with a 
 reflux condenser were placed 68 g. of phenoxy butyl alcohol 
 and 190 c.c. of liydrobromic acia(sp. gr. 1.57). The reaction 
 mixture was refluxed for five hour’s after which 35 c.c. of 
 

 
 
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- 13 - 
 
 concentrated sulfuric acid were added. 2he refluxing was then 
 continued for five hours. 200 c.c. of water were added and the 
 reaction mixture extracted with ether. This was washed with a 
 10p sodium hydroxide solution and then distilled under dimin- 
 ished pressure. 41 g.(4?^ theory ) of te tramethylene bromide were 
 obtained, boiling at 93-100° under 20 mm. pressure. 34 g. 
 
 (36,j theory) of phenoxy butyl bromide then distilled (153-157° 
 at 22 mm. ) . 
 
 She results of other runs were as follows: 
 
 Yield 
 
 Hun *jnt. alcohol Aint.48^hBr Arnt.hr 30^ Dime 2e tramethylene liienoxy 
 
 Bromide Butyl 
 
 Bromide 
 
 1 
 
 52 
 
 £>* 
 
 70 
 
 c.c . 
 
 11 
 
 c.c. 
 
 2 
 
 hrs. 
 
 27 fo 
 
 58.5 f 0 
 
 2 
 
 50 
 
 g* 
 
 40 
 
 c.c. 
 
 10 
 
 c.c. 
 
 
 hrs. 
 
 13 $ . 
 
 465 ?. 
 
 3 
 
 53 
 
 g* 
 
 140 
 
 c.c. 
 
 25 
 
 c.c. 
 
 9 
 
 hrs. 
 
 42 % 
 
 46 fj 
 

- 14 - 
 
 iiuinmary 
 
 Lianne slum reacts with phenoxy propyl bromide to form 
 phenoxy propyl magnesium bromide ( to a limited extent ) , un— 
 saturated compound, and diphenoxy hexane* 
 
 nn attempt was made to ascertain the best conditions 
 
 offt-chlori tc acid* 
 
 A relatively cheap method was developed for the pre- 
 paration of tetramethylene bromide and phenoxy butyl bromide. 
 
- 15 - 
 
 Eibliography 
 
 1. jour. £. prakt. Ch.em.(2) 39, 543(1889) 
 
 2. Compt. rend. 152 » 345(1901) 
 
 5. Ber. 39, 4119(1906) 
 
 4. ^our. Biol. Ch.em. £7, 443(1916) 
 
 5. Ber. 24, 2640(1891)