Patented Oct. 26, 1948 2,452,350 UNITED STATES PATENT OFFICE 2,452,350 METHOD oF PRE PARNG ALKY ESTERS OF CHOROACET CACD William P. Bitler, Haverstraw, Thomas C. Asch ner, Stony Point, and Leonard Nicholl, Nyack, N. Y., assignors to Kay-Fries Chemicals, Inc., West Haverstraw, N. Y., a corporation of New York No Drawing. Application March 20, 1945, Serial No. 583,83 4 Claims. (C1, 260-487) 2. This invention relates to improvements in the methoxyacetic acid methyl ester have been found process of preparing methoxyacetic acid methyl unsatisfactory, ester and, more particularly, to a novel process of Methoxyacetic acid ester has been prepared by preparing the intermediate chloracetic acid the reaction of chloroacetic acid with sodium methyl ester. 5 methylate to form the methoxyacetic acid sodium The preparation of alkyl esters of alkoxyacetic salt. This step is followed by acidification to lib acid, other than the methyl ester, has long been erate the methoxyacetic acid formed, then foll known. One of the most feasible methods pro lowed by esterification of that acid with methanol. posed involves the preparation of chloroacetic The disadvantage of this process is that an extra alkyl ester, followed by the reaction of the ester 0. mol of sodium methylate is needed to neutralize with sodium alkoxide. In the case of chloroacetic the chloroacetic acid. Also, the free methoxy acid ethyl ester, the equations involved would be acetic acid formed must be concentrated and the as follows: salt liberated, filtered off, before esterification (1) ClOHCOOH + C.H.OH - C1CHCOOCH + H2O steps can be started. 5 Yet another process involves the reaction of (2) CICHCOOCH + NaOCH - methoxyacetic acid prepared from carbon dioxide CHOCHCOOCH -- NaCl and diethyl ether, under high pressure. Here, However, when this particular synthesis is ap high pressure is a great disadvantage, and di plied to the methyl ester of methoxyacetic acid, methyl ether is highly flammable. certain difficulties arise. The first step according 20 It has also been proposed to start with methyl to Equation 1 is carried out as by esterification ene glycol and carbon monoxide, using an acid of chloroacetic acid with methanol by flashing the catalyst to obtain the ester directly at tempera methanol through the reaction mixture, or by re tures below 100° C. However, here again, high fluxing the chloracetic acid with methanol con pressures are required of the order of 30 to 700 tinuously, and continuously vaporizing approxi atmospheres. mately an equal total weight of methanol and Another proposal found in the patent literature water of reaction from the reaction mixture, or is the reacting of glycolic acid and dimethyl ether by adding methanol, and refluxing the reaction in the presence of an acidic catalyst, such as a mixture for some definite period of time, and mineral acid or borontrifluoride. Here again, the then following by distillation of the methanol and 30 dimethyl ether, being flammable, is a fire hazard, water of reaction, a large proportion of chloro and this hazard is enhanced by the presence of acetic acid methyl ester being distilled over with the gaseous boron trifluoride. the distillate. Owing to the fact that methanol We have now found that the prior art disad boils at a temperature so much lower than the vantages can be overcome by the use of high boil water of reaction, this gives a distinct disadvan 35 ing esters of chloroacetic acids which will permit tage, as it renders it hard to get a high propor the water of esterification to be easily removed, tion of water in the distillate. Now, these two and without any high proportion of ester being conditions, which appear to be peculiarities of entrained. Suitable reagents for this purpose are this reaction mixture, make it necessary to intro the alkyl, aryl and aralkyl mono ethers of ethyl duce an expensive recovery step for the recovery 40 ene glycol. The mono ethers of ethylene glycol of the ester which has come over with the meth are known under the trade name of "Cellosolve.' anol. This extra step must be followed by sepa Our preferred reagent herein is monoethylene ration of the ester from the water in the metha glycol mono butyl ether. Other suitable reagents nol. Such separation can only be accomplished 45 include those alcohols which will form sufficiently by fractionating the methanol and water mixture high boiling esters with chloroacetic acid as to away from the chloroacetic acid methyl ester by give products having the desired vapor pressure means of an entraining agent, such as benzene. relationship or, stated in other language, such Because of the fact that water forms an azeo esters as will not form azeotropes with the alcohol trope with the chloroacetic acid methyl ester and the methanol during the distillation, it is impos 50 and water, or with the water alone. Direct cata sible to effect the separation of the water from lytic esterification, using mineral acid as a cata the other components by simple distillation. This lyst is proposed. The equation for this reaction difculty has been found to be not quite so pro is as follows: nounced with the higher aliphatic esters. (3) (CHOCHCHOH) BuoCHCH-OH- CICH,CooH Other methods proposed for the preparation of BuoCHCH.OOCCH.C.--H.O 2,452,850 3 4 The second step of the novel synthesis involves carbonate and the reaction mixture was then vac the preparation of chloroacetic acid methyl ester uum-distilled. by ester exchange between monothylene glycol The distillation data is as follows: nonobutyl ether chloroacetate or other chloros - . acetic acid esters of higa boiling alcohols, and 5 vap methanol. A mineral acid, such as sulfuric acid, Temp ressure rt. Remarks may again be used as a catalyst. This reaction is , Degrees f. sists: f s "as Methylene glycol monobuty chloroacetate in the presence of the catalyst. The 10 Ins Ethyleneslycol chloroacetic acid methyl ester which is formed is 133-36 32-31 83 Product:tee Monoethylene e glycol vaporized with the methanol and removed from Ronobutyl ether chloroacetate. the reaction mixture, being condensed along with ------the entrained methanol. Re-fractionation of this Tests of the product produced showed 91.5% as distilled-over mixture permits the easy separation 15 the monoethylene glycol monobutyl ether chloro of chloroacetic acid methyl ester from the meth- acetate. This corresponds to a yield of 94.5%, of anol, since chloroacetic acid methyl ester and theory. methanol only do not form a constant boiling mixture. Also, due to the fact that no water is ESTER ExCHANGE now present, the danger of hydrolysis is con- 20 Methyl chloroacetate is then prepared by ester pletely eliminated. The monoethylene glycol exchange between the monoethylene glycol mono monobutyl ether reformed at this point remains butyl ether chloroacetate and methanol. The re behind in the reaction vesseland can be separated agents used were: fromion. anyThe residualequation methanol for this rections by simple asfractiona follows: 25 Mogethylene glycol mono butyl etherGrams W chloroacetate-2 mols------, 390 (4) BuOCHCHOOCCHC - CHOH - Methanol (400 cc.).------38 BuOCHCH-OH -- ClCHCOOCHs ConC, Sulfuric acid- --- 3 The chloroacetic acid methyl ester formed ac- These reactants were placed in a one-liter flask cording to Equation 4 is then reacted with sodium 30 equipped with a still-head. Methanol was flashed methoxide to give the methoxyacetic acid, methyl through, and methanol and methyl choloroace ester. This reaction is effected by adding the tate continuously distilled from the reaction mix chloroacetic acid methyl ester to a slight excess of ture as the methanol was added. The distillation the sodium methylate dissolved in methanol. table of this step is as follows: When the reaction has been completed, the salt 35 ------which has precipitated is filtered off. The prod- Liq. vap. vol. Meth. vol. of uct is separated from any accompanying meth- Temp. Temp. Added Distiate ano by simple fractionation. Any further incre------

ments of salt which may be precipitated during 10:00 Per ce, Per ce the fractionation are also separated by filtration. 40 1636. O ---356 The equation for this reaction is: : ...... ".s 28 S. XCHOH 12:30. 89 600 1, 170 5 CCHCOOCH--- CHON - CHOCH.CooCH + NaCl as The distillate, which contains the methyl chloroacetate, was fractionated through a three The novel discovery herein will thus be seen to foot column packed with glass beads, and gave the overcome or avoid a difficult peculiar to the for- following results: %. - mation of the lower chloroacetic acid alkyl esters 715 g. (900 cc.) methanol byThe simple quantitative esterification. data supporting the work de- 50 25 g product B. P. 26-28 C (98% ester by scribed above is as follows: hydrolysis) . PREPARATION OF METHoxyacetic ACID METHYL The residue in the flask, when fractionated, gave 3. ESTER Grams Reagents 55 Monoethylene glycol monobutyl ether------176 Grams Monoethylene glycol mono butyl ether cho CH3CICOOH (5 mols)------25 roacetate ------73. BuoCHCH-OH (6 mols)-20% excess.-- 7100 This proves that the ester exchange had not been Conc. ESO------5.0 completed up to that point. It required merely ...... 60 continuous treatment or flashing with methanol The reaction herein was carried out by heating through the reaction vessel until esterification thereagents two-liter ask while continuous was completed. It will be see that the reaction ly distilling of the water of reaction. The course progresses easily and that the methyl chloroace of the reaction is shown in the subjoined tables, tate distills over with the methanol in relatively ------high proportion. It will be seen further that the T Temp.Liq, Temp.Yap, PressS. DistilledS. CompleteReaction methanolmethyl chloroacetate. can be readily separated from the C. Degrees Mn. Percent PREPARATION OF METHOXYACTIC ACE METHY, 4. 109 99 760 ------w ESTER :40. In , . 50 100 60 80 8 70 12:10 p.m.... O 100 60 85 95 Sodium methylate and methyl chloroacetate were reacted to form methoxyacetic acid methyl The final acidity of the reaction mixture ap- ester. To carry out this reaction, 108 g. of methyl proximated 0.3 mol. The residual acidity in the chloroacetate (1 mol), 23 g. sodium, and 396 g. reaction mixture was neutralized with sodium 75 methanol (500 cc.) were reacted in the following 2,452,850 S manner: The methyl chloroacetate was added to sulfuric acid as a catalyst, to give a mixture of a solution of the sodium in methanol, and over a . monoethylene glycol monoalkyl ether and chloro period of half an hour, with moderate cooling. acetic acid methyl ester plus methanol; and frac The temperature of the reaction mixture was tionating the chloroacetic acid methyl ester in maintained between 30 to 40° C. An hour after 5 methanol from the monoethylene glycol mono this reaction period, the alkalinity measured alkyl ether to give pure chloroacetic acid methyl showed that one-half the Original amount of S0 ester in substantially water-free non-hydrolyza dilum was still unreacted. The reaction mixture ble condition, . was then refluxed in a water bath for two hours, 3. The method of preparing water-free chloro cooled down, and tested. At this point, but slight acetic acid esters comprising the steps of esterify alkalinity was noticed, proving that the chlorine ing monoethylene glycol monoalkyl ether with had been Substantially completely reacted with chloroacetic acid to form monoethylene glycol the Sodium. The sodium chloride formed was . . monoalkyl ether chloroacetate plus water, frac filtered off as a precipitate and the filtrate Con tionating the product to remove the water and taining the reaction mixture was fractionated. 15 monoethylene glycol monoalkyl ether and an in The distillate contained methanol, 390 g., and an termediate fraction containing the monoethylene ester fraction boiling at 20-130 C, under a pres glycol monoalkyl ether and a small amount of sure of 760 mm. On redistillation, this product ester, leaving a product comprising the pure yielded 75 g. of material boiling at 126-128° C. monoethylene glycol monoalkyl ether chloroacea This product showed a specific gravity of 20 tate; then reacting this monoethylene glycol (21 monoalkyl ether chloroacetate with an excess of 1.0526 ( methyl alcohol to give the chloroacetic acid ester and monoethylene glycol mono alkyl ether; frac and an ester number of 99.5%, as methoxyacetic tionating to remove the chloroacetic acid ester acid methyl ester. The yield of this compound, and the alcohol, and removing the alcohol from based on the original weight of methyl chloro the distillate to give a water-free chloroacetic acetate used, was 78%. acid ester. It will thus be seen that by the improved 4. The method of preparing water-free chloros method herein, where the intermediate com acetic acid esters comprising the steps of esteria pound methyl chloroacetate is prepared under e fying monoethylene glycol monoalkyl ether with conditions precluding hydrolysis of the products chloroacetic acid to form monoethylene glycol of reaction, the separation of methoxyacetic acid monoalkyl ether chloroacetate plus water, frace methyl ester, and of methoxyacetic acid alkyl tionating the product to remove the water and esters generally, as greatly and unexpectedly en monoethylene glycol monoalkyl ether and an in hanced and the products made available as a termediate fraction containing the monoethylene commercially practical material, with a simple 3 5 glycol monoalkyl ether and a small amount of process involving a mere ester exchange and a ester, leaving a product comprising the pure minimum of chemical treatment and mechanical monoethylene glycol monoalkyl ether chloroace handling steps. s tate; then reacting this monoethylene glycol What is claimed is: monoalkyl ether chloroacetate with an excess of 1. In the preparation of methyl chloroacetate, 40 an alcohol of the group consisting of methyl, the improvements comprising reacting monoeth ethyl, propyl, butyl and isoamyl alcohols to give ylene glycol monobutyl ether and chloroacetic the chloroacetic acid ester and monoethylene acid, in the presence of a mineral acid as a cata glycol-monoalkyl ether; fractionating to remove lyst, to form monoethylene glycol mono butyl the chloroacetic acid ester and the alcohol of the ether chloroacetate, then reacting the monoeth group consisting of methyl, ethyl, propyl, butyl ylene glycol monobutyl ether chloroacetate with and isoamyl alcohols, and removing the alcohol an excess of methanol, in the presence of sul from the distillate to give a water-free chloro furic acid as a catalyst, to give a mixture of mono acetic acid ester. ethylene glycol monobutyl ether and chloroacetic 50 WILLIAM P. BITER, acid methyl ester plus methanol; and fractionat THOMAS C. ASCHNER. ing the chloroacetic acid methyl ester in methanol from the monoethylene glycol mono butyl ether LEONARD NICHOLL, to give pure chloroacetic acid methyl ester in REFERENCEs CITED substantially water-free non-hydrolyzable con 55 dition. The following references are of record in the 2. In the preparation of methyl chloroacetate, file of this patent: m the improvements comprising reacting monoeth UNITED STATES PATENTs ylene glycol mono alkyl ether and chloroacetic Number Name Date acid, in the presence of a mineral acid as a cata O 1,433,308. Steffers.------. Oct. 24, 1923. ; lyst, to form the chloroacetate of monoethylene 1695,449 Bannister ------Dec. 18, 1928 glycol mono alkyl ether, then reacting the chloro 1987,227 Britton et al ------Jan. 8, 1935 acetate of monoethylene glycol monoalkyl ether 2,226,599 Zellhoefer et al. Dec. 31, 1940 with an excess of methanol, in the presence of 2,257,021. Pollack ------sept. 23, 1941

S. Certificate of Correction Patent No. 2,452,350. October 26, 1948. WLLIAM P. BITLER, ET AL. numberedIt is hereby patent certifiedrequiring that correction errors appearas follows: in the printed specification of the above Column 3, line 47, for the word “difficult' read difficulty; line 59, for “Conc. HSO,' read Conc. HSO; column 4, line 9, in the first table, third column thereof, for “ethyl' read ether; line 38, in the second table, second and third columns thereof, readfor “Per is greatly; cent' both occurrences, read Degrees; column 5, line 34, for “as greatly' and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office. Signed and sealed this 5th day of April, A. D. 1949.

SEAL

THOMAS F. MURPHY, Assistant Oommissioner of Patents.