United States Patent (19) (11) 4,129,595 Suzuki 45) Dec. 12, 1978 (54) PREPARATION OF CHLOROACETYL (56) References Cited CHLORDE PUBLICATIONS E. E. Blaise et al., Comptes Rendus (France), vol. 174, 75 Inventor: Shigeto Suzuki, San Francisco, Calif. pp. 1173-1174, (1922), (Chem. Abstr., vol. 16, 2480). 73) Assignee: Chevron Research Company, San Primary Examiner-Gerald A. Schwartz Francisco, Calif. Attorney, Agent, or Firm-D. A. Newell; John Stoner, Jr. (21) Appl. No.: 891,429 57 ABSTRACT Chloroacetyl chloride is prepared by reacting glycolic (22) Filed: Mar. 29, 1978 acid with thionyl chloride in the presence of nitrogen 51) int. C.’.............................................. CO7C 51/58 containing organic compound orphosphine compound. 52 U.S. C. ................................................ 260/544 Y 58 Field of Search .................................... 260/544 Y 3 Claims, No Drawings 4,129,595 1. 2 glycolic acid with thionyl chloride in the presence of a PREPARATION OF CHLOROACETYL CHLORDE catalytic amount of nitrogen-containing hydrocarbyl organic compound or hydrocarbyl phosphine com BACKGROUND OF THE INVENTION pound at high conversion and yield in accordance with 1. Field of the Invention 5 the present invention. The present invention relates to the preparation of chloroacetyl chloride. More particularly, the invention DETALED DESCRIPTION OF THE relates to the preparation of chloroacetyl chloride by INVENTION reacting glycolic acid with thionyl chloride in the pres The nitrogen-containing hydrocarbyl organic com ence of nitrogen-containing organic compound or phos 10 pounds or hydrocarbyl phosphine compounds which phine compound. provide the catalyst in accordance with the present 2. Description of the Prior Art invention are characterized primarily by hydrocarbyl Comptes Rendus, Volume 152, page 1601, dated June groups which have a total of not more than 10 carbon 6, 1911, shows the preparation of alkyl chloride by the atoms in the case of the nitrogen-containing hydro reaction of alcohol and thionyl chloride in the presence 15 carbyl organic compounds or not more than 30 carbon of a molar amount of pyridine as acid acceptor. atoms in the case of the hydrocarbyl phosphine com Comptes Rendus, Volume 174, page 1173, dated May pounds. Although for present purposes hydrocarbyl 1, 1922, shows the production of chloroacetylglycolyl groups are preferred, there may be substituents which chloride by reaction of glycolic acid and thionyl chlo are known to be chemically inert to the glycolic acid ride. 20 and thionyl chloride reactants. Survey of Organic Synthesis by Buehler and Pearson, The nitrogen-containing hydrocarbyl organic com pages 860 and 861, published 1970 by Wiley-Inter pound catalysts in accordance with the present inven science, New York, shows the production of acyl chlo tion include amides, imides, amines, quaternary ammo rides by reaction of the acid and thionyl chloride em nium salts and ureas. The preferred catalysts are the ployed with iodine or with a trace of pyridine. 25 U.S. Pat. No. 2,848,491 shows the preparation of N,N-disubstituted amides such as N,N-dimethyl form carboxylic acid chlorides by reaction of the acid with amide, N-methylpyrrolidone, etc., the N-monosub phosgene in the presence of nitrogen-containing com stituted amides such as N-methyl formamide, N-methyl pounds and mentions the preparation of chloroacetyl acetamide, etc., the tertiary amines such as pyridine, chloride from chloroacetic acid. 30 triethylamine, etc., secondary amines such as pyrroli U.S. Pat. No. 3,418,365 shows the preparation of dine, diethylamine, etc., and substituted ureas such as beta-chloropropionyl chloride by the reaction of beta tetramethyl urea. propiolactone with thionyl chloride. The hydrocarbyl phosphine compound catalysts in U.S. Pat. No. 3,758,659 shows the preparation of accordance with the present invention include trihydro chloroacetyl chloride by reaction of ketene with chlo-35 carbyl phosphines and phosphine oxides having the rine in the presence of alpha-butyl-gamma-butyrolac formula tone. R2 U.S. Pat. No. 3,880,923 shows the preparation of / mono-chloroacetyl chloride by reaction of acetyl chlo and R-P ride and chlorine in sulfuric acid. 40 N3 U.S. Pat. No. 3,883,589 shows the preparation of O R. chloroacetyl chloride by reaction of ketene and chlo rine in the presence of a tertiary phosphate ester such as in which R, R and Rare hydrocarbyl groups which tris(2-chloroethyl) phosphate. may be the same or different and contain a total of not 45 more than about 30 carbon atoms. Included are tributyl SUMMARY OF THE INVENTION phospine, triphenylphosphine, dibutyl-n-phenylphos In accordance with the present invention, a process is phine, and tri-n-octylphosphine oxide. provided for preparing chloroacetyl chloride which The proportion of the catalytic nitrogen-containing comprises reacting glycolic acid with thionyl chloride hydrocarbyl organic compound or hydrocarbyl phos in the presence of a catalytic amount of a nitrogen-con 50 phine compound in accordance with the present inven taining hydrocarbyl organic compound having a total tion is found to be critical and must be kept low in the of not more than about 10 carbon atoms or hydrocarbyl range of amounts sufficient to provide the catalytic phosphine compound having a total of not more than reaction of glycolic acid and thionyl chloride. For pres about 30 carbon atoms, maintaining the reaction at a ent purposes the catalyst should be in amounts not more temperature and for a time sufficient to convert the 55 than about 0.15 mols per mol of glycolic acid and pref. glycolic acid to chloroacetyl chloride, and separating erably in the range of 0.001 to 0.1 mols per mol of gly chloroacetyl chloride. colic acid. By way of contrast, when the basic nitrogen Typical alcohols and carboxylic acids when heated containing hydrocarbyl organic compounds are pre with thionyl chloride with or without a basic nitrogen pared in approximately molar amounts as acid accep containing organic compound such as pyridine as acid tors, it is found that the reaction is completely inhibited acceptor in stoichiometric amounts will give, respec and no chloroacetyl chloride is obtained. tively, the corresponding alkyl chlorides and acyl chlo The glycolic acid is reacted with thionyl chloride in rides. By way of contrast, glycolic acid, which has both stoichiometric amounts. Thus, one mol of glycolic acid an alcohol hydroxyl group and an acid carboxylic is reacted with 2 mols of thionyl chloride. Excess thio group, when heated with thionyl chloride gives com 65 nyl chloride may be employed if desired. plex mixtures of products, none of which being chloro The temperatures of the reaction of glycolic acid and acetyl chloride. Accordingly, it was not expected that thionyl chloride are over a wide range. An advantage of chloroacetyl chloride would be obtained by reaction of the process lies in the employment of moderate temper 4,129,595 3 4. atures which minimize the need for heating and cooling during the reaction. For present purposes temperatures EXAMPLES in the range of from about 20 to about 100 C. are pre The process of the present invention is illustrated by ferred. the following examples. Unless otherwise specified, the The times required for reaction of glycolic acid and 5 proportions in the examples are on a weight basis. thionyl chloride will vary over a wide range, in general with the higher temperatures providing shorter reaction EXAMPLE 1. times and lower temperatures providing longer reaction A 100-ml, 3-necked round-bottom flask, equipped times. At about 100° C. the reaction is substantially with a magnetic stirrer, a condenser, and a thermome complete in about 30 minutes, while at room tempera- 10 ter, was charged with 2.9 grams (0.04 mol) of dimethyl ture a longer time of about 60 minutes may be required. formamide and 36 grams (0.30 mol) of thionyl chloride. The reaction of glycolic acid and thionyl chloride in This solution was stirred at room temperature and 7.6 accordance with the present invention is conveniently grams (0.1 mol) of glycolic acid was added in small carried out by contacting the reactants and the catalyst increments over a period of 5 minutes. Then the result in the liquid phase. If desired, inert solvents may be 15 ing reaction mixture was stirred at room temperature employed to facilitate handling of reactants. Suitable for 18 hours. At the end of this time, an aliquot was solvents include acetyl chloride, 1,2-dichloroethane, analyzed by NMR. This analysis showed greater than chlorobenzenes, benzene, hexane, and the like. The 99% conversion of glycolic acid and a 98% yield of chloroacetyl chloride product of the reaction is readily chloroacetyl chloride. The remainder of the reaction mixture was distilled in a vacuum still at 100 mm Hg to separated from the reaction mixture by conventional 20 give 9.5 grams (84%) of chloroacetyl chloride having a means, as for example by distillation. boiling point in the range of 46' to 50 C. Other preparations were carried out by a similar procedure. The composition of the reaction mixture and 25 the results are given in Table I. TABLE I PREPARATION OF CHLOROACETYL CHLORIDE REACTION MIXTURE AND CONDITIONS RESULTS Glycolic Thionyl Conversion Yield of Chloro Ex. Acid Chloride Time Temp. of Acid acetylchloride No. Additive (moles) (moles) (moles) (hrs) (C) (%) (mole %) 2 none u- 0, 0.3 2.5 80 >99 Ote 3 none u- 0.1 0.3 24 22 >99 One - - - 0.3 48 22 Ole 10.5 grams ZnCl2 - --- m 2 180 trace - - -r 194 trace 4 pyridine 0.2 0.1 0.2 1 105 >99 Oe 5 pyridine 0.0 0.1 0.3 2 22 - < 1 --- -- - 2 80 - >95 6 dimethylformamide 0.04 0. 0.3 22 - < 1 -- - m 3 22 -- 12 -- - - r 65 22 - 50 --- -- - P 90 22 - >98 7 dimethylformamide 0.04 0.1 0.3 22 - <, Ow- - 3 22 - - - 1 80 - >98 8 dimethylformamide 0.013 0.1 0.3 2 22 - < 1 - - - 90 22 - >95 9 dimethylformanide 0.005 0.