Ethyl chloroacetate, hydrolysis

Much interesting work has been done in the last ten years on the bridging of pyrrole and piperidine rings. Early in their work on this subject Clemo and Metcalfe (1937) prepared quinuclidine (V) by the reduction of 3-ketoquinuclidine (IV), the latter resulting from the hydrolysis and decarboxylation of the product (III) of a Dieckmann internal alkylation, applied to ethyl piperidine-l-acetate-4-carboxylate (II), itself made by condensing ethyl piperidine-4-carboxylate (I) with ethyl chloroacetate. 

In an attempt to prepare ethyl 3-indolylacetate (225) by the action of ethyl chloroacetate on indole magnesium iodide, only unidentified oily products were obtained under a variety of different experimental conditions. However, when indole magnesium iodide was treated with ethyl -chloropropionate in other, a product, identified as 3-[)3-(l-indolyl)propionyl]indole (226) by its behavior on alkaline hydrolysis and by the number of active hydrogen atoms it contained, was obtained. ... 

Concentrated alkali hydroxide decomposes the acetoacetic acid produced by hydrolysis of the ester in a different manner. The cleavage does not take place between the carboxyl group and the rest of the molecule, but between the latter and the —CO.CH3-group, so that two molecules of acetic acid are produced. This acidic hydrolysis introduces a new variation into the synthesis as a whole. The practical importance of this acid hydrolysis may be illustrated by the same example, the condensation product of ethyl acetoacetate with ethyl chloroacetate. 

Ethyl chloroacetate, C4H7CIO2, is used as a solvent and in the synthesis of intermediate dye chemicals. The effluent from a dye synthesis plant is discharged into a wetland, with a pH of 7.3. At this pH, the alkaline hydrolysis rate constant is 1.56 M s . If the alkalinity of the wetland is close to constant, compared with the concentration change of the ethyl chloroacetate, at 0.002 M, what would be the first-order rate constant for ethyl chloroacetate degradation ... 

The Darzens reaction of isatin with ethyl chloroacetate yields glycidic esters. Alkaline hydrolysis of the glycidic esters yields indole-2,3-dicarboxylic and indole-3-carboxylic acids in a 6 1 proportion. The isolation of two isomeric glycidic esters, and the fact that both produce the indolecarboxylic acids in the same proportion led to a mechanistic proposal for the formation of the later through a common intermediate439 (Scheme 101). 

Bourne [45] investigated two parallel competive reactions the simultaneous neutralization of HCl and the alkaline hydrolysis of ethyl chloroacetate with NaOH ... 

Ring closure of 7V-(carboxymethyl)amide oxime yields 4//-l,2,4-oxadiazin-6(5//)-ones 3. The required acids are obtained by treatment of 1,2,4-oxadiazol-5(4f/)-ones with ethyl chloroacetate in the presence of potassium carbonate, followed by hydrolysis. The cyclization proceeds in good yield in the presence of dicyclohexylcarbodiimide in pyridine or dioxane.12... 

Alkyl substituents can be introduced into heterocyclic rings also via direct ONSH reaction with the Grignard reagents [72] or via the VNS reaction with carbanions of a-chloroalkyl carboxylic esters [17], followed by hydrolysis and decarboxylation [95-97]. For example, treatment of 5-nitroisoquinoline with the carbanion of ethyl chloroacetate under the standard VNS condition in DMF in the presence of t-BuOK gave the expected (5-nitroisoquinol-6-yl)acetate, which was transformed into 6-methyl-5-nitroisoquinoline via hydrolysis and decarboxylation (Scheme 23) [95]. 

Cyclopropane derivatives can be prepared by several methods. Michael addition of the enolate of ethyl chloroacetate to ethyl acrylate generated the cyclopropane ring in 7.223 via addition to form a carbanion and internal expulsion of the chlorine moietyl Manipulation of functional groups allowed selective reduction to 7.224 and conversion to 7.225 (as a mixture of cis- and trans-isomers). Rearrangement and hydrolysis led to c/s-2-(2-amino-l-cyclopropyl)ethanoic acid, 7,226. The analogous cyclobutane derivatives were also prepared by a similar route. 

In 1977, Komiyama and Bender (98) also studied the validity of the charge-relay system in serine proteases. They examined the general base-catalyzed hydrolysis of ethyl chloroacetate by 2-benzimidazoleacetic acid as a model system. 

Dichloroacetic acid is produced in the laboratory by the reaction of chloral hydrate [302-17-0] with sodium cyanide (31). It has been manufactured by the chlorination of acetic and chloroacetic acids (32), reduction of trichloroacetic acid (33), hydrolysis of pentachloroethane [76-01-7] (34), and hydrolysis of dichloroacetyl chloride. Due to similar boiling points, the separation of dichloroacetic acid from chloroacetic acid is not practical by conventional distillation. However, this separation has been accompHshed by the addition of a eotropeforming hydrocarbons such as bromoben2ene (35) or by distillation of the methyl or ethyl ester. 

Glycine ethyl ester hydrochloride has been prepared by the action of absolute alcohol and hydrogen chloride on glycine from glycyl chloride and alcohol by the action of ammonia or hexamethylenetetramine on chloroacetic acid, and subsequent hydrolysis with alcoholic hydrochloric acid and by the action of hydrogen chloride and alcohol on methyleneamino-acetonitrile. ... 

Bromoacetic acid has been prepared by direct bromination of acetic acid at elevated temperatures and pressures,2-3-4 or with dry hydrogen chloride as a catalyst 6 and with red phosphorus as a catalyst with the formation of bromoacetyl bromide.6-7-8-9-19 Bromoacetic acid has also been prepared from chloroacetic acid and hydrogen bromide at elevated temperatures 6 by oxidation of ethylene bromide with fuming nitric acid 7 by oxidation of an alcoholic solution of bromoacetylene by air 8 and from ethyl a,/3-dibromovinyl ether by hydrolysis.9 Acetic acid has been converted into bromoacetyl bromide by action of bromine in the presence of red phosphorus, and ethyl bromoacetate has been... 

Fig. 19- The efficiency, q, of the Amberlite IR-120 ion exchanger catalyst in ester hydrolysis as a function of the entropy, S, of the parent hydrocarbon RH or R H of the substituents, (a) Hydrolysis (at 25—45°C) of methyl esters RCOOCH3 [366] 1, acetate 2, chloroacetate 3, benzoate 4, cyclopentanecarboxylate 5, phenylacetate 6, a-naphthylacetate 7, 1-octanoate. (b) Hydrolysis (at 35°C) of acetates CH3COOR [480] 1, methyl 2, ethyl 3, cyclopentyl 4, cyclohexyl 5, 1-butyl 6, 2-pentyl 7, 1 -pentyl 8, 1 -hexyl 9, 1 -octyl,...

Apart from ethyl acetate, the least reactive ester studied is N,0-diacetyl serinamide, which is hydrolyzed in a pH-independent reaction between pH 7 and 8 with a rate coefficient193 of 2.66 x 10-5 sec-1. Salmi and Suonpaa194 and Palomaa et al. 9S, have measured the rates of neutral hydrolysis of a number of chloroacetate esters, and this work has been extended more recently by Euranto and Cleve196-198, who have measured the activation parameters for the hydrolysis of several compounds. Motfat and Hunt199 have obtained the same data for the hydrolysis of a variety of alkyl and aryl trifluoroacetates, and the data for substituted phenyl acetates191 have been plotted in Fig. 14. Most of the available data are collected in Table 27. 

Tetrahydro-lf/-l,3-diazepine-2-thiol (73), when heated with ethyl chloro-acetate, gives 74 while the reaction of 73 with chloroacetic acid in aqueous medium affords 3-(<5-aminobutyl)thiazolidine-2,4-dione (75) [Eq. (21)], via initial generation 74, followed by hydrolysis.94 Substituted 2-mercapto-imidiazolines undergo similar ring transformations.95-97... 

Ethoxyacetic acid was first prepared by Heintz by the reaction of chloroacetic acid with sodium ethylate. The procedme described above is essentially that of Sommelet. Ethoxyacetic acid has also been prepared by hydrolysis of ethoxyacetonitrile with concentrated hydrochloric acid and by the action of excess sodium ethylate on 1,1,1,2-tetrachlorethane and on a,/3-dichloro-vinyl ethyl ether. A recent patent reports a synthesis from diethyl ether and carbon dioxide at high pressure. 

---