Brigham Young University BYU ScholarsArchive

Theses and Dissertations

1947-04-01

The preparation of certain organic chloroformates and carbonates

Robert E. Brailsford Brigham Young University - Provo

Follow this and additional works at: https://scholarsarchive.byu.edu/etd

BYU ScholarsArchive Citation Brailsford, Robert E., "The preparation of certain organic chloroformates and carbonates" (1947). Theses and Dissertations. 8175. https://scholarsarchive.byu.edu/etd/8175

This Thesis is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. THE PREPARATI OH OF CERTAI N 0RG.1NIC CHLOROFORJ.'\Ll.TES AND CARBON T

Thesis ubmitted to the Department of Chemistry Brigham Young University

~ ...... "') .~ . ~ . "')...... , ...... : : ....: . ..-. ~ ..·.: : ..: ...• : ·.. ~ . : ,.. .~ : :. : ·: : ··.... ; ~ : ·. : : .: . : . : : : ••• .... •." •,.r_·: -••• ~ ....

In Parti a l Fulfillment of the Re~uirements for the Degree Master of cienoe

147143 by Robert E. Brailsford .tipril 1947 This Thesis by Robert E. Brailsford is accepted in its present farm by the Department of Chemistry of Brigham Young University as satisfying the ·rhesis requirement for the degree of Master of Science. PREFACE

flhile working for the Hooker Electrochemical Company of Niagara Falls , New York , from April 3 , 1943 , to January 30 , 1946 , the writer became interested in organic chloroformates and. carbonates , an interest instigated by requests from B. F . Goodrich Company for a number of samples . fter returning to Brigham Young University that preliminary interest was revived and the experi - mental work of this thesis was performed. under the direction of Dr . Charles ' . :Maw and Professor Joseph K. Nicholes . The writer wis hes to thank these men and Dr . Loren C. Bryner for their kind assis tance in proof readin g this thesis and offerin g numerous suggestions for its improvem ent . TAELE OF CONTENTS Page

I 1'TRODUCTI ON • • • • • • • • • • • • • • • • • • 1

1 CARBONYL CHLORIDE , PREP_ RA.TIOU AIID USE • • • • • 2 HI ST RY, PREP}1.R.nTION, AlID .. OP:ERTIES OF TH · ORG m:c CHLOROFORMATES~ ND G RBOILTE • • • • 5 OTHER ·:ET HODS OF PREP A!w.TI ON • • • • • • • • • • 14

USES • • • • • • • • • • • • • • • • • • • • • • 16 EXPERI1 ":NTAL ' ORK • • • • • • • • • • • • • • • • 18

m. ARY • • • • • • • • • • • • • • • • • • • • • • 25

LITERATURE CITED • • • • • • • • • • • • • • • • 29

PPElillIX Table I. hysical Const an ts of Known :Mono- Chloroformic Esters Table II . Physical Const ants of Known Organic Carbonates Table III . Prepared Organic Carbonates

Fi g ure I . J ..ppara tus Utilized INTRODUCTION

The preparation of organic carbonates and formates was of considerable laboratory interest during the latter part of the nineteenth century; , but no practical use was made of them. It has now been revived by industrial companies such as t-he :a. F. Good.rich Company and the Hooker Electroahemioal Company. These companies are interested primarily in finding new compounds which can be utilized as intermediates or plasticizers in the plastic and rubber industries. At the present time the primary concern is with the organic chloroformates, which are prepared by the same method as are the carbonates but at a lower temperature. In 1945 the Goodrich Company developed a use for allyl ohlorofo.rmate. This company called upon the Hooker Company to devel op a practical method for preparing and furnishing them with this compound . This problem was accomplished by Edward Belmore , a chemical engineer, in cooperation with the author. 1 Some further work was done upon two or th.ree of the well known aliphatic carbonates. 2

1 Belmore , Edward , and Brailsford, Robert , The Preparation of Allyl Chlo.roformate, a Research Pap~fo.r the Hooker Electrochemical Company, Patent Pending . 2 Work by the ant ho.r under the direoti on of Dr. B. Wojcik , Hooker Electrochemical Company, 1945. 2

Upon returning to Brigham Young University; the author decided to continue this research on org anic ohloro- f'ormates and carbonates for a master's thesis. There are very few organic aromatic carbonates mentioned in the literature. This gave added interest to oontinue the research. The organic chlo.rofo.rmate s are colo.r •less, llnpleasant smelling liquids and ,• f'or the most part, very strong laomymators due to their chlorine content and ease of hydrolysis. The carbonates, on the other hand , are very agreeable smelling liquids or crystalline solids. 3

C_RBONYL CHLORIDE,PREPARATION AND~

The present disoove.ry and industrial preparation of' organic chloroformates and org anio carbonates waited upon the discovery and knowledge of how to use carbonyl ohlo.ride. In 1812 Sir Rn.mph.ray Davy first prepared carbonyl chloride by exposing a mixture of carbon monoxide and chlorine to light: 4 Cl / co 0 = C + - 'Cl

3 Fieser, Louis , and Fieser , Mary, Organic Chemistry (Boston: D. C. Heath and Company, 1944), pp. 178-9. 4 Ibid. 3

This reaction is reversible . At 800° C the phosgene is broken d~1n into its components . 5 Davy gave carbonyl chloride its common name phosgene beaause of its prepara - tion by the influenoe of light (phos , Greek - -light; gene.re , Latin - -born} . 6 Phosgene is still manufactu..red by Davy ' s method using activated charcoal as a catalyst . On a small scale phosgene can be made from carbon tetrachloride and eighty percent pyr,osulfurio aoid ; 7

-,- --- COClz +

Pyrosulfuryl chloride is the by- product . This method was used during the war years of 1914 - 18 in Italy and France but was later abandoned in favor of the synthesis from carbon monoxide and chlorine; the method used in Germany . A high yield of phosgene is obtained , but much chlorine is consumed . 8 In the laboratory , phosgene is readily prepared by the oxidation of chloroform with cb.r omic acid mixtu..re:

+ 30 2COClz + HzO + Cl2

5 Karrer; Paul , Organic· Chemistry (New York: Nordeman Publishing Company, Inc .; · 1938); pp . 203-4 . · 6 Fieser ,·, Louis , and Fieser , Mary; 2.£.• cit ., p . 178 . 7 Whitmore; F~ank., Or,anio Chemistry (New York: D. Van Nostrand Company; Inc ., , 1942 , pp . 516-7 . 8 Sartori, Mario , The War G~ses (New York: D. Van Nostrand Company, Inc ., 1939,p. 62. 4

Chlorine ancl ohloroform contaminate the phosgene prepared

by this method. 9 Chloroform is oxidized to phosgene to some extent by the air in the presence of light. This is one reason why chloroform as an anaesthetic has been largely abandoned . Phosgene is a poisonous , suffocating gas at normal temperatures.· It is about ten times more toxic than chlor- ine as a lung injurant. It has an odor that resembles that of mouldy hay. It boils at a° C and fumes in air if moisture is present , due to hydrolysis with the formation of carbon dioxide and hydrochloric acid .l o

H 0 = COClz + 2 + 2HC1 Because of its poisonous character and the ease with whi~h it can be prepared , liquefied, and transported, phosgeneI proved very effective in World War .I. Introduced by the Germans in 1915, it was loaded in shells and bombs which exploded upon striking the ground . It was responsible for approximately eighty percent of the gas casualties of the War, for even though it is inh aled deeply, there are no warning symptoms for as long a period as two hours . Injurious physiologioal action in the body is due to the hydrochloric acid formed by hydrolysis of the phosgene .

~ i'irrer , Paul , ~- cit., p . 204 . 10 Ibid. 5 Cl , - Phosgene, C-0, is the acid chloride of carbonic Cl ,. aoid, HO,C:::-0 reacting similarly to other acid chlorides HO " - ' with water , alcohols, amines , etc. which contain active hydrogen. 11 It also reacts readily with dimethylaniline to give Miohler ' .s ketone, an important intermediate in the makin g of triphenyl methane dyes, as is illustrated by the following eg_uation:1 2

-I- =

This commercial use far phosgene increased the quantity of the gas , making it available as a war gas.

HI STORY, PREPARATION, 1~ PROPERTI~S OF THE ORG.b.NIC CHLOROFOR1\rIAT7fil AND CARBO 1 T'.iES

fte~ the preparati on of phosgene by Davy in 1812 chemists beg an to use it to treat a variety of different compounds. In 1833 Dumas treated ethyl alcohol with this gas and obtained ethyl chloroformate:1 3

COC12 + = + HCl

11 Reid, E. Emmet, College Organia Chemistr~ (New York: D. Van Nostr and Company, Inc., l93l), pp . 27 -so. 12 Sartori, Mario, ££• cit., P • 62. 13 Bernthsen , A., A Textbook of Orean ic Chemistrl (New York: D. Van Nostr anu Company, Inc., 1931) ,, p . 289 . 6

This aompound was found to be a volatile liquid with a very disagreeable pungent odor . The physical p~operties of the known mono-ohloroformio esters are recorded in Table I ; those of the carbonates , in Table II .

T.he reaction vf.i.th an a lcohol can be conducted in two stages , and either the above mentioned mono or the dialkoxy derivative can be prepared by the proper adjustment of the proportions and the reaction conQitions . 14 In preparing the chloroformates phosgene is used in excess , ana the reaction takes place in the cold . At higher temperatures and with the alcohol in excess the chloroformate fir st formed reacts to form the carbonate :

= + HCl

Phosgene reacts similarly with aromatic alcohols and :phenols . wli th one molecule of phen ol and one of :phosgene phenyl chloroformate is formed :

+ a1coc1 + HCl with two molecules of phenol , diphenyl carbonate : 15

14 Sartori , Mario , £2.• oit ., pp . 70- 71 . 15 Ibid- . 7

+ ClCOCl + + HCl

During the first , orld War a research p.r cg.ram was instigated to pr ot ect troo ps against ph osge n e poisoning . This research resulted in the discovery that it reacted with sodium :phen ol ate to f o.rm diphenyl carb onate . Sodium phenolate placed in the filters of the gas masks furni shed excellent pr otection •16 The first series of compounds formed by the reaction between ph osgene and alc ohols , the ohloroformate s , have a mixed nature . They are chloroformic esters , and als o acid chlorides, and react similarly . Ii th an other molecule of an alc ohol they react slowly to form carbon ates as mentioned above . With a ll other acti ve hydrogen compounds , such as water , ammoni a , primary and secondary amines , they a lso .react . For example , the mono ethyl chloroformate is characteri sti c . Wit h ammoni a or a substituted ammonia it introduces the carbethoxy group {C00C2H5 ) i nt o the nitrogen compoun d to form urethanes . 17

16 W'hitmo.re., Fr ank , ~ • cit ., p . 517 . 17 Fieser , Louis , anQ Fieser , 1,ary , 2.£• cit ., :p. 179 . 8

Furthermore , it has been found that ethyl and methyl chloroformat es oan be very useful in protecting phenolic hydroxyl groups . In 1932 Bergmanl 8 published a general method for the synthesis of poly peptides tha·t has been of the greatest signifioance . The essential feature of this new method is the masking of the amino group with the carbobenzyloxy group (C6H5CH20co-), which can be removed from -the peptide by catalytic hydrogenation at room temperature with but few exceptions . By use of this new synthesis peptides containing even complex amino a cids have been syn thesize d. Carbobenzoxy chlori de, whioh is benzyl chloroformate , is readily prepared by treating benzyl alcohol in toluene solution with phosgene :

The condensation with the amino group is usually accom- plished in an alkaline solut ion . 19 Phosgene , when left in contact with acetone ~or one half hour and then distilled, forms isopropenylchloroformate (Acetone is represented by its enolia formula): 20

l8 Ibid , p . 365 . 19 Ibid . 20 Matuszak , Iv., Joul'nal of meric a n Chemica l ociety, 56:2007, 1934 . 9

+ ClCOCl = + HCl

This compound is a powerful lachrymator , a :property which all the ohloroformates possess in greater or less degree . By the . action of phosgene on ethylene glycol at ordinary temperatures , glycol carbonate is formed according to the equation:

CH20H CHzO, I -i- = c=o 2HC1 CH 0..,. + CH20H 2

This is an example of the individual molecule forming a carbonate with two of its own hydroxyl groups and not with a hydroxyl group on another molecule . 21 It seems that whenever the compound which is treated with phosgene has two or more hydroxyl groups of its own the reaction is with two of them . As a further example , glycerol reacts with phosgene to yield glycerol carbonate .

-i- = + 2HC1

Substances like pyridine absorb the hydrochloric acid fo.rmed . 22

21 artori , Mario, .Q:Q.• cit ., p . 71. 22 Ibid . 10

By bubbling gaseous phosgene through ethylene mono-chlorohydrin at o° C,AJ- chloroethylchloroformate is formed, Cl OCOCHCH Cl, a colorless, irritating liquid 2 2 which is hydrolyzed by alkaline solutions. 23 .t ordinary temperatures phosgene reacts with -mono chlorohydrin forming the carbonate,

yH 20 '-. 9Ho - c=o , a colorless, heavy CHzCl

liquid, sparingly so·luble in water •24

I~MES

urtz, Roese, Ladenburg, · iohelhaus, chreiner, and others 25 synthesized the abo ve mentioned chloroformic esters and neutral carbonate esters during the latter part

of the nineteenth century. Today many of them are mentioned only in German literature. For example, Schreiner , Roese , and Pawlewski prepared several mixed carbonate esters. 26 They first prepared the mono chloroi'ormio -ester by means of the alcohol and phosgene . Another radical was then

added · by means of the sodium or potassium a lcoholate.

23 Nemurowsky , J., 11 ction of Phosgene upon Glyco- chlor ohydrin, n Amerioan Chemical Society , VI-VIII: 144, 1885. 24 Matuszak , M., 2£• cit., p . 71. 25 Beilstein , F.; Hanclbuch

By this means they prepared ethyl methyl carbonate , propyl methyl oa.rbonate , and iso-butyl methyl carbonate . These are all pleasant smelling liquids . Reid 27 refers to the preparation of propyl ethyl carbonate as outlined. above and as represented by the following equation :

+ = + HCl

After forming mixed esters Roese28 found that he could replace th e lower molecul ar weight radic al with the higher one. He first prepared th~ mixed ester:

+ - '1- NaCl

He then added ethyl a lcohol and at highe~ temperatures an d in an acid solution, the methyl radical is replaced. .

+ +

Beilstein refers to the added work of two chemists , Fatianow and Pawlewski 29 who prepared ethyl phenyl carbonate by two slightly different methods . The former · utilize d the familiar method of re a cti ng ethyl chloroformate and

27 Reid , E. Emmet, .£12.• cit ., p . 280 . 28 Beilstein , F., 212.• cit ., p . 541 . 29 Ibid ., II:663, Df96 . 12 potassium phenolate . The latter used phenol and ethyl chloroformate with aluminum chloride as a catalyst . How- ever , the physical constants of thei.r products do not check . The boiling points and specific gravities vary considerably . In an advertisement in a l ate issue o~ the Chemiaal and Engineering~ ' Columbia Chemicals advertises three aliphatic carbonates which they have prepared . These compouna:.s are di - glycol allyl carbon.ate , but oxyethyl diglycol carbonate , dimethyl carbonate , and a chloro - formate , diglyool chloroformate . 30 nether company advertises the preparation of another mixed carbonate , quinine ethyl carbonate . 31 Interest in these compounds is increasing . Increase d numbers of compounds with variation of properties can be obtained by the reactions which the carbonates and especially the chloroformates undergo .

Chlorination of both readily takes place at the o< - radical . Methyl chlorofo.rmate was chlorinated during the first orld Viar to trichlor omethyl chlor of or mate and then used as a "Lung injurantn war gas . 32 It hydrolyzes to phosgene .

30 Chemical and Engineering News, 25:99 , No. 2 , January 13, 1947. - - 31 Ibid ., 24:18 , No. 1 , January 10 , 1946 . 32 Lowry , Harrow , and pfelbaum , An Introduction to Organic Chemistry (New York : John ·~tiley &Sons, Inc ., 1945"), p . 256 . 13

Perohloro-dimethyl oarbonate, ) , ethyl carbonate, (cc13 2co3 C03 {c2c15 )2 ; tetraohloro-diethyl carbonate , co3 (c2H3c12 }2 , and di(pentachloro) ethyl oarbonate, co3 (c2c15 )2 , are also readily preparea. 33 When the neutral carbonate esters a.re heated. • with phosphorus pentaohlo.ride an alkyl group is eliminated. ith a mixed ester it is always the radical with t-he fewest carbon atoms which is replaoed., as illustrated by the following equation: 34

- -~ +

Nenoki 35 in 1895 enunciated the principle that if phenols were made into stable esters like phenyl-salicylate, they woL1ld pass through the stomach wi t .hout damage to the tissues and by hydrolysis become effective antiaeptics. Three carbonates, thymol carbonate, guaiacol carbonate, and. creosote carbonate, were prepared and utilized for this pul'pose but did not prove as effective as originally expected. The creosote is obtained from the destructive distillation of wood and is a comple x mixture composed

33 Beilstein , F., ~• cit., p . 542 . 34 von Richter, Vioto:r ; Organic Chemistrt (Philadel- phia : P. Blakistorls Son & Company, 1905), p. 38. 35 Jenkins and Hartung, The Chemistry of O~ganic :M:edioinal Products (New York: John iiley and Sons , Inc., 1941), pp. 261-2. 14 chiefly of guaiacol and cresol . These carbonates are also used in the treatment o:f tuberculosis and c.h:J:tonic bron - chitis as expectorants and germicides . 36

OTHER METHODS OF PREP RATION

Clermont , Schreiner , Roese, 1u.rtz , Ladenburg , and Wiohelhaus 37 investigated several other methods :for the preparati on of organic carbonates . Their work seems to be limited to the preparation of the diethyl carbonate and one or two of the other similar carbonates de.rived from the lower membered alcoh ols of the aliphatic series . Clermont 38 prepared the neutr al carbonic acid esters by the re a ction of alkyl iodides and silver- cal'bonate . Eernthsen 39 refers to this method of preparation , pointing out only that ethyl carbonate is formed by the a ction of ethyl iodide upon silver carbonate:

+ = 2.AgI -t-

This method should be investigated further because the silver used in the reaction oan be recovered . The expense

36 Goodman and Gilman , The Pharmacological Basis of TheraP,eutics (New York : The Macmillan Company, 1944} , p . 819 . 37 Beilstein ,. F., .212..• cit ., p . 541. 38 Beilstein ; nnerri vate der Kohlensaure ,n ££.• cit ., I:719 , 1881 . 39 Bernthsen , . • , .212..• cit ., :p. 289 . 15

of the silver compound , however , limits this method to a laboratory scale . 40 Wu..rtz developed an other method for the preparation of the diethyl ester . He .reacted alcohol with cyanogen chloride . A solution of the cyanogen ahloride in absolute alcohol after a few days contains the ester , the a oid ester , and some ethyl chloride . Mul d.er 41 gives the reaction thusly :

He reported further that c yanogen bromide coul d not be used in place of the chloride . This method is worthy of further study if the cyanogen chloride is available . The .reaction possibly could be speeded up by a cat a lyst . Beilstein briefly men~ions two other methods , one developed by Chancel in 1851 and the other by Ladenburg and , ichelhaus . 42 In the first two intermediate compounds are formed , potassium ethyl sulfate and potassium ethyl carbonate . These compounds .react to yield ethyl carbonate and potassium sulfate :

40 Beilstein ; op. cit ., II:541 , 1896 . 41 Ibid. 42 rorcr. 16

H 0 , C H 0 , C2H 0, c2 5 ,,,,o 2 5 5 ,, C: O = C: O K2 04 KO / + KO ,,,, / + 0 C2H50 • The seoon:1 method 1•equires the preparation of an intermediate compound , or tho - formic ethyl ether . This compound then reacts with bromine; in accordance with the following :

+

So many products makes this method impractical .

USES- The reactions of ethyl chloroformate have been summarized in a late issue of the Chemical and Engineering News43 . The a.rtiole st!'esses hov, important this chemic al will become as an intermediate in the futlll'e for the rapid and efficient manufactu.r e of many import ant ind us tria 1 and medicinal :products . The following reactions are d.i scussed in addition to many already listed : It forms condensation pr aiucts with ethyl iodide in the :presence of metallic sodium to produ~e ethyl secondary - butyl ketone; it reacts

43 Chemical am Engineering News , 24:17 - 18 , No . 1 , January 10 , 1946 . 17

with G.rignard reagents to give ethyl benzoate , triphenyl carbinol , and triethyl carbinol; with allyl iodide in the presence of zinc , it gives among other prcrlu~ts triallylcarbinol; and it .reacts with benzene in the presence of aluminum chloride to give ethylbenzene . s p.r•eviously .referred to , guaiacol and. creosote 44 carbonates are utilized as intestina 1 antiseptics . Whereas the phenols are irritant , toxic , and unpleasant tasting compounds , the carbonic acid esters of phenols are insoluble and non - toxic to the stomach tissues . When administered , they are slowly h;ydrolyzed in the intestinal t.raot with the gradual liberation of the phenol . Due to the low concentration and the distribution of phenol its toxic effects are almost negligible . 45 For some years diethyl carbonate has been used as a • 46 solvent for nitrocellulose in the lacquer ind. ust.ri es . As intermediates , solvents , plasticizers , and modifiers these chemicals are increasingly being called into service . 47

44 Jenkins an~ Hartung , .9.l?_• cit ,, pp . 261 - 2 . 45 I bid . - 46 Gara.rd , Ira D., An Introduction ~ Organic Chemistry (New York: John iley and. Sons, Inc ., 1932) , p . 122 . 47 Chemioal and Engineering News, 24 :17- 18 , No. 1 , January 10 , 1946 . 18

EXPERIIvENTAL ·,NORK

Due to ~ifficulties in obtaining commercial q_uantit ies of phosgene ,· preliminary exp eriment al work consisted in choosing a meth od of preparation and setting up an apparatus for the generation of phosgene . The method decided upon was the .react ion of carbon monoxide and chlorine ,- with li ght and activated charcoal to serve as catalytio agents . This is the pr incipal industrial method used at the present time . Suggestions for the second phosgene generator were obtained from the book The iva:r Gases , by Mario Sartori . Figure I is a drawing of the seaond phosgene generator set . up and used . It consists of a cylinder of chlo.rine (A) , a three - necked flask (B) where the carbon monoxide is generated , two bubble ,flasks , {C) and (D) , to dry the gases , a flask {E ), conde nser (F) , and a second flask (G) where the gases combine d, and the final set - up (H) where the esterification takes place . The condenser is filled with activ ate d ch ar coa l . This cat a lytic effect is reinforced by a 150- watt li ght pl aced by the mixing flasks and cond enser . The first phosgene generator was similar , except that very little drying reagent was used in the bubble 19 flasks , and there was no mixing flask before the condenser containing the .charcoal . Into the small three - necked fl a sk , which contained concentrateq sulfuric acid , formic acid was added dropwise from the separatory funnel . Carbon monoxide was formed readily as shown by the reaction equation :

HCOOH + = co +

The sulfuric acid in the bubble flasks dryed both the oarbon monoxide and the chlorine , which intimately mixed and reacted in flasks E and G and the condenser :

co + =

Sa.rt or i 47 specifies the rate of adding the gas as five t o six bubbles of chlorine per second and eight bubbles per second for carbon monoxide . Thi s suggestion was followed rather clos~ly . Flask H contained the reacting alcohol and the generated phosgene was bubbled into it . The temperature of the first few reactions was 60 to 70° c. Later reactions at lower temperatures gave better results .

47 Sartori , Aario , 2P..· cit ., p . 62 . 20

Table II shows that most of the work was oarried out with the aliphatic alcohols , except four or five of the carbonates and two of the mixed carbonates . The present work; for the most part , was carried out with aromatic aloohols . Ten .runs were made , using the first .:phosgene generator and. several diff e.rent alcohols . The alcohols used were °' - naphthol , p- ni t.rophenol' , methyl salicyla t e , p - chlorophenol , ethylene chlorhydrin , and benzyl alcohol .

These r ea cti ons , except .in the ca se of o<.- naphthol , gave poor yields . One mol of p- nitrophenol reacted with one mol of five percent sodium hydroxide . Phosgene was then bubbled through the solution at a temperature of 60° C. The result was negative; no carbonate formed . P- nit.rophenol was obtained . The explanation of this negative result was later determined . Phosgene was bubbled through methyl salicylate at a temperatu:re of 50 to 60° C. .As a product , salicylic acid was obtained , showing th a t only hydrol ysis of the ester took place . In another run the ester was treated with sodium in order to obtain the sodium methyl salicylate , but when heat was applied in order to inorea se the fo.rmati on of the alcoholate a violent reaction took place and only salicylic acid was identified . 21

Ethylene chlo.rohyd.rin did not react with phosgene under these conditions and benzyl alcohol was chlorinated to benzyl chloride and benzol - trichloride , two compounds that are very readily iQentified because of their boiling points and. lach.rymatory properties .

A positive reaction resulted with o<.. - naphthol . This compound resembles phenol but is a stronger acid and dissolves in aqueous sodium carbonate . The sodium salt was prepared. and phosgene added . The temperature was kept between 40 ard 50° c. The black color of the sodium

~ -naphthylate solution gradually turned grey and then colorless while a dark orange red oil formed . Phosgene was passed th.rough the mixt u.re for four hours and then the mixture was allowed to stand overnight . Col orless crystals were obtained from the red oil which had solidified . These we.re .recrystallized from alcohol . At this point , because of the low yields obtained , the second completely new phosgene generator was set up .

T.wo e1•ro.rs , which seemed to aontribute to the inefficiency of the s ystem ;, had to be eliminated . One was insufficient drying for the generated gases , and the second was imp.roper mixing of the two gases before going over the activated charcoal catalyst . 22

Phenol forms a well-known carbonate derivative . Thus it was tried first in o.rde.r to test the new phosgene generator . One mol of soQium phenolate in 200 ml. of water was placed in the three-necked flask and phosgene was bubbled th.rough at room tem:peratl.ll'e fo.r two hours. The crystals of diphenyl carbonate that forme d were washed , filtered, dried , and recrystallized from alcohol . The melting point checked with the value in lit e.ratur ,e, 81 to s2° c. Table III shows the aarbonates prepared anQ their physical constants. Runs were next made with p-chlorophenol, p-nitrophenol, benzyl alcohol , o-a resol , ethyle ne chlorohydrin, thymol, o-ohlo.rophenol and resorcinol. P- and o-chlor ophenols, p-nitrophenol, o-cresol, and resorcinol gave good results; with the formation of well defined crystals. 0-chloro- ca.rbonate and p-nitro carbonate readily crystallized from hot alcohol, but p-chlor o carbonate and o-cresylic ca.rbonat e are more soluble in a lcohol which necessitated a water and alcohol mixture for recr ys tallization. ResorcinOl carbonate was very difficult to recrystallize , proving insoluble in all the common reagents, alcohol , ether, carbon tetrachloride, and. toluene. 23

Benzyl alcohol formed a number of compounds with chlorination predominating; which indicates that the phosgene was contaminated vdth chlorine . Benzyl chloride and benzo - trichloride were identified by their boiling points as th e lower fractions of the distillation . Benzyl chloride boils at 179° and benzo -triohloride at 214° c. The temperature q_uiakly rose to 260° , and two small fractions we.re obtained , one at 260 to 270° and another at 270 to 280° C. Although not pure , these fractions contained some dibenzyl carbonate , because upon treating with hyd.roohlo.r ,io acid carbon dioxide was evolved . 11 the crystalline carbonates were tested with hydrochloric acid , and each one evolved carbon dioxide . T-o conf irm the results; each was fi .rst fused with NaOH and then made acidic with hydrochloric acid . Then when heated , they all gave up carbon dioxide which formed cal cium carbonate in a lime water solution . ith excess carbon dioxide the calcium carbonate was ch anged to the soluble bicarbonate whioh ; upon heating , again precipit .ated as the insoluble calcium carbonate . Resoroinol could react in one of two ways with phosgene . Either t wo molecules c·ould react together to form the di - resorcinol carbonate , 24

C:>- oH ClCOCl + HO-<=> OH + OH

0 I/ <=>-0- C- O-<=> + 2HC1 OH OH or it could .react intermolecularly to form resorcinol carbonate :

OH Cl , C: 0 OOH+ Cl _..... - o:>=o + 2HC1

Aliphatic di - hydroxy or t:.ri - hydroxy alcohols such as the glyo ols or glycerol react intermolecularly , similarly to the above equation . 48 In order to pr ave which way resorcinol reacted , a molecular weight determination was made . pproximately 50 mg. of the compound was melted with one - half gram of pure c amphor . It was then cooled , powdered , and a melting point determination made . Because of the large molar lowering of the melting p oint of camphor of 39 . 7° C the molecular weight of the compound is easily dete.rmined . 49 Results of 129 and 145 (true v a lue , 136)

48 ~ atuszak; l. • , ~ • cit . , p . 2007 . 49 Fuson , Schriner , T~Systernatic Identifia ation of Organic Compounds (lirew Yor'k: John ·,Jile y and Sons , Inc ., 1940) , P • 122 . 25 0 shows that resorcinol carbonate , ' C:O , is the 0 / resulting compound . The other carbonates were identified als.o Tiith molecular weight determinations , in addition to melting points and the evolution of carbon dioxide . The _average results of the molecular weight determinations and the melting points of the prepared carbonates are listed in

Table III .

1 n effort was made to determine if the reaoti on ,

,- -I- 2 gI would take place if an aromatic halide such as mono- iodobenzene or mono- ahlorobenzene were substituted for the ethyl iodide . Carbonates a.id. not form d.u.r ing the several attempts made. Ethyl chloride in place of ethyl iodide also gave negative results .

SUkir RY

In a late issue of the Chemical and Engineerin~ News there is an article called nwho Iakes It? 11 in which the mou.r Research Foundation wishes to know if some company oan furnish them with a number of rare chemicals . ~mong these compounds are listed alkyl chloroformates . 50 This

50 Chemical and Engineering News, 24:278 , No. 2 , January 25 , 1946 . 26 is only one example of the mounting interest being shown in these compounds . , Here is a branch of organic chemical research that has been investigated very little and promises to be a fruitful field . Certai n companies and research workers can see possibilities of huge expansion in the number and variety of organic chloroformates and carbonates obtainable . l ·any of these compounds will readily find. uses as inter - mediates , plasticizers , modifiers , and medicines . This brief discussion and research pa~er attempts to correlate a large portion of the information about" the preparation of known organic chloroformates and. carbonates , to point out the present and possible future uses of these compounds , and to contribute s orne inf o.rmation concerning the preparation of a number of the organic carbonates .

A comparison of the difi'erent methods of preparation is made . Of these methods only that of phosgene reacting with the alcohol or sodium alcoholate seems to be indus- trially feasible at the present time . It may continue to be the only important large - scale method for preparing these compounds , although the use of cy anogen chloride is worthy of research . The use of silver carbonate proved unsatisfactory , es p ecially in the case of the preparation of the aromatic carbonates . 27

ethods of preparing phosgene were studied and the one considered as the most practical for the preparation of carbonates was set up and used . This method , the catalytic reaction of chlorine and carbon monoxide , worked ., very well . Nothing new was oontributed to this method , but this work showed that the phosgene can be used without previous isolation and purification . The objective of the experimental work was obtained in the preparation of a number of aromatic organic carbonates . These were diphenyl carbonate, di - naphthyl carbonate , di - o- chlo.rophenyl carbonate , di-p-chlorophenyl carbonate , di-p-nitrophenyl carbonate, di-o-cresylic carbonate, and resorcinol carbonate . Except for diphenyl carbonate, which is very well known,and di - 6- cresylic carbonate (di - o- tolyl carbonate)Pl these other carbonates do not appear in literature . If made recently by companies doing research on this problem , they have not as yet been publicized . They are all crystalline solids, whioh have faint , pleasant , aromatic odors . Even though recrystallized twice , the di - p-nitrophenyl carbonate is odd in having an odor whioh resembles maple syrup .

51 Huntress , Mulliken , Identification of Pure Organic Compounds (New Yo..11k: John Wiley & Sons , Inc . -;-J.94IT, p . 288 . LI TERATURECITED 147143

29

LITERATURE CITED

Beilstein , F., Handbuc~ der Or~anischen Chemie . Volume I , 1881; Volume I , 3rQ er., 1 93; Voi . II , 1896. Bernthsen , A., . Textbook of Organic Chemistry. New York: D. Van :Nostrand Company , Inc ., 1931. Chemical and Engineerinff News , Volume llV , No. 2, January 13 , 1947;7Jol.ume mv , o:-r, January 10 , 1946 . Davis on , For41:'est R., Synopsis of Materia Medioa , Toxicology , and Pharmacology. St . Louis : The c. V. 1osley Company , 1"'9"44. Fieser , Louis , and Fieser , ~ary , Organic Chemistry . Boston: D. C. Heath and Company , 1944 . Fuson , Schriner , The Systematic Identification of Organic Compounds . New York: John Wiley and Sons , -rnc ., 1940.

Garard , Ira D., An Int.roduotion ~ Orga nic Chemistry . New York: John iUley and Sons , Inc ., 1932 . Goodman and. Gilman , The Pharm a cological Basis of Therapeutics . New York: The acmillan Company , 1944. - Huntress , 1ulliken , Identification of l!U'e Or~ania Compounds . New York: John Wiley and Sons , ""Tnc:;-194 .

Jenkins , Hartung , The Chemistr4 of Organic Tuedicinal Products . New Yo.r·k: John Wiley and ans,, Inc ., 1941 . Karre.r , Paul ,· Organic Chemistry . New York: Nord.eman Publishing Company , Inc ., 1938 .

Lowry , Harrow, and Apfelbaum , ~ In t roduction to Organic Chemistry . New York: John Wiley and Sons;Inc ., 1945 . Iatuszak , Tu., Journal of j _me.rican Chemical ociety , Volume 56 , 1934 . -

Nemlll'owsky , J . ,· n cti on of Phosgene upon Glycolchlor ohyd.rin , 11 American Chemical Society , Volumes. VI-VIII , 1885 . 30

Reid , E. Emmet,- College Organic Chemistry . Hew Yo.rk: D. Van Nostrand. Company, Ino ., 1931. Sartori , Mario , The ~Var Gases . New York: D . Van Nostr and Company, Ina :-;- 1939'". von ichte.r , Victor , Organic Chemist.r~ . Philadelphia : P . Blakiston ' s Son and Company, 1 05 . Whitmore , Frank , Organic Chemistry . New Yo.rk: D. Van Ifostrand Company , Inc ., 1942 . APPENDIX .TABLE I PHYSICAL CONSTANTSOF KNO"iVNMONO-CHLOROFORMIC ESTERS

NAME FORt.,.!ULA STATE BOILING SPECIFIC SOLUBILITY POINT 0 c GRAVITY iO

Methyl chloroform.ate CH30COCl Li~. 71 1.22-3 s-1.s. Hz o s. or Ez• sol • Ethyl chloroformate CzHf20COCl .. 93-95 1.135 i.HzO It

Propll chloroformate C~H:zdCOCl It 11.4-116 1.090 d.inH20 It

' tt tt II Isobuti:1- chloroformate ~CH3)2CHCH20C0Cl 130 1.040 Isopropenil chloroform.ate CH2:C(CH3)0COCl " 93i746mm 1.103 i.H20 tt

It II -chloroethyl chloroformate ClCHzCH20COC1 " 152i7s2mm 1. 382-5 Allll chloroformate 9¾:CHCHzOCOCl tt 112 1.12.35 tt " - Tri-chloromethll chloroformate Cl~COCOCl tt 128 1.652:5 d. inHzO ti TABLE II

PHYSICAL CONSTANTSOF KNOWNORGANIC CARBONATES

NAME FORMULA ST.A.TE MELTINGOR SPECIFIC SOLUBILITY 0 20 BOILING PT. c GRAVITY i

Di-methyl carbonate CH30C02CH3 Licq. 90 1.0650 i.HzO s.org. sol. Di-ethyl W C2H50C02C H ff. 12:6 o. 9751 fi. W 6 2 5 Di-propyl C3H70C02CgH7 w 168 0.949 ff ff Di-n-butyl w C4H90C02C4li9 ft 207/7ZOmm 0.92A4 w W · Di-sec-butyl ff ff ft 178-180 - W ft 5 11 Di-iso-but~l W " ii· 190 o. 9191 ff Di-iso-amy . ft n 226 0.906 15 • w Glycol ft· s:ol. 3'.9 chlo~o lycerol . liq. 157 10mm 1.550 Perchloro dimethyl sol. 78-9 Ethyl methyl li~. 109.~ 1.002 Propyl ft • 1&0~8 0.978~1 Iso-butyl l ii 8 fl 143.6 O. 951Z7 EthylL phenyl w 11 234 1.1170° 200-210 1.1134° " " • ,...,.,u~n,.,{),,,,.,_ -u ~ m.L s;ol. 89-91 sl. s.H 0 ~ 2 ft 80-81 i. H~O 8 49 Gu~ia~ol : · {C6§(0CH3j0)2CO ; 86-88 Di-o-tplyl CH3C6H40C02CsH4CH3 60 Di-m-tolyl '! 11 W , 4.9 Di-p~-~~ol1_l ~ ff w 114 ~- ff TABI.E III

PREPAREDORGANIC CARBONATES

NAME FORMULA STATE MELTING Mol. Wt. (ave) Mol. Wt. SOLUBILITY POINT 0 c OBTAHTED Theory

Di-phenyl carbonate cfiH~oco,c6H5 sol. 81° 217 214 i. H20 s.org.sol. Di-na.phthyl carbonate C1qHzOCO2C1QH7 n 117-120° 305 314 tt tt Di-p-nitrophenyl carbonate . N0206H t.PCOa C~4NOz lt 66-68° 310 304 It " Di-o-chlorophenyl ,. carbonate ClC§I¼OC02CBli4Cl lt 60° 276 283 tt " Di-p-ohlorophenyl carbonate tt n 134- 136° 284 283 tt Di-o-oresylic " carbonate CH~CgH40C02CgH4CHiIt 60-62° 238 242 .. tt Resorcinol carbonate C6H402CO " 82-84° 137 136 ti i. " ...... ' ., ,...... " ...... ·. .. .. ·...... •' ...... ~· •• C' . . .. .·····.;; .·...... , ...... •J.. • .. .. .• • {J • . ... .•" . . . ' .. •• , . .• ...... ' ...... ------

r-- '' / . .J I 4 , - L I I O /,";' ·.\ . · 11/1l I ,- ~ / c::.::::::::.-- ... _// I -~~~, ,,------i

I 0

/.'.: ·�

rt

·- ·• - -- p F 1 \ - P ·• \

...... J ...... >044 ) � -·�------...... -·

0