Ethyl dichloroacetate, hydrolysis

Imidazole will function as a general base in the hydrolysis of acyl-activated esters such as ethyl dichloroacetate Qencks and Carriuolo, 1961) and esters where the p/STg-value of the leaving group is 2-3 units lower than that of ethanol and methanol such as... 

The slow step of this process is often the initial nucleophilic displacement, and although the alkaline hydrolysis reaction (Y = HO ) is unique in that only a single displacement is involved, the step concerned is the same as the ratedetermining step for the reaction with many other nucleophiles. Kinetically, therefore, the reactions are comparable. A second important type of catalysis by nucleophilic reagents does not involve direct attack by the nucleophile on the ester. For example, the hydrolysis of ethyl dichloroacetate is catalyzed by aniline, and no anilide is produced in the reaction186, viz. 

General base catalysis of ester hydrolysis by nucleophiles other than amines and oxyanions has not been characterized, though it would be expected to be closely similar to the reaction involving these bases. Cyanide ion, for example, would be expected to catalyze the hydrolysis of ethyl esters with activated acyl groups, such as ethyl dichloroacetate, by this mechanism. 

Figure 2.5 The Br0nsted plot for the general-base catalysis of the hydrolysis of ethyl dichloroacetate. The logarithms of the second-order constants obtained from the plot of Figure 2.4 are plotted against the pAT s of the conjugate acid of the catalytic base. The slope is the /3 value. Note that the points for amine bases ( ) fall on the same line as those for oxyanion bases (O), showing that the catalysis depends primarily on the basic strength of the base and not on its chemical nature.

Fiqure 2.4 Determination of the rate constants for the general-base catalysis of the hydrolysis of ethyl dichloroacetate. The first-order rate constants for the hydrolysis are plotted against various concentrations of the base. The slope of the linear plot is the second-order rate constant (k2). The intercept at zero buffer concentration is the "spontaneous hydrolysis rate constant for the particular pH. A plot of the spontaneous rate constants against pH gives the rate constants for the H+ and OH" catalysis. It is seen that pyridine is a more effective catalyst than the weaker base acetate ion. [From W. P. Jencks and J. Carriuolo, J. Am. Chem. Soc. 83,1743 (1961).]... 

Fig. 4. General base-catalysed hydrolysis of ethyl dichloroacetate [8]. The figure illustrates uncorrected (O) and corrected ( ) points 1, water 2, HCOj 3, PhNH2 4, acetate 5, pyridine 6, succinate dianion 7, 4-picoline 8, phosphate dianion 9, imidazole 10, trishydroxymethylaminomethane.

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. 

The imidazole-catalysed hydrolysis of polar substituted 2,4-dinitrophenyl acetates (21 X = Cl, OMe) has been investigated at different temperatures. The observed rates correspond to the bimolecular nucleophilic addition of the imidazole at the carboxylic carbon atom followed by a very fast hydrolysis of the (V-acetylimidazole in water. The influence of polar substituents in the acid moiety of the ester molecule on the hydrolysis reaction can be described by an electrostatic dipole-dipole interaction in the same way as the neutral hydrolysis of polar substituted ethyl acetates. By the use of both quantum and classical dynamics, a study of the neutral hydrolysis of 4-methoxyphenyl dichloroacetate (22) in water concluded that the rate-determining step is a proton transfer concerted with formation of a C-O bond. ... 

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