Alkaline hydrolysis of esters

The carbonyl group reactivities in thiophenes and benzenes are very similar, as shown by the similar rates of alkaline hydrolysis of esters and by the great similarity of the thiophenealdehydes to benzaldehyde in numerous carbonyl group reactions. This has been ascribed to the counteracting —I- -M effects of the thienyl group in this kind of reactions. ... 

Table 1 Rate coefficients k2, enhanced rate ratios re, ring size and activation parameters for the alkaline hydrolysis of esters in 70% (v/v) aqueous dioxan at 20°C. 

The first observation of carbon acid participation in the alkaline hydrolysis of esters was reported in 1970 by Bowden and Last (1970, 1973b). The 8-acetyl-, 8-propionyl- and 8-isobutyryl-l-naphthoates [43] reacted rapidly in aqueous dioxan containing an excess of base. However, the immediate products of these reactions are the phenalene-l,3-diones [44], The two... 

Sharma, R.C. and Sharma, M.M. Kinetics of alkaline hydrolysis of esters. II. Unsaturated esters and oxalic esters. Bull. Chem. Soc.Tpu, 43(3) 642-645, 1970. 

The alkaline hydrolysis of esters has been studied in more detail, or at any rate more frequently, than any other chemical reaction, and results continue to appear in a steady stream. Since the gross mechanism is not in real doubt, this discussion will be limited mainly to the relationship between structure and reactivity in the reaction. The relationship can in most cases only be discussed for the overall reaction, which is, of course, of most immediate practical importance. Although it is of great interest to discover what effects structural changes may have on the separate steps of the reaction, it is only in the few cases where the oxygen exchange and hydrolysis reactions have been measured concurrently that this is possible. 

Most of the generalizations that can be made about the relationship between structure and reactivity in the alkaline hydrolysis of esters are familiar. They will therefore only be summarized here, and illustrated by a selection from the vast amount of available data (Tables 31 and 32). 

The effects of polar substituents on the alkaline hydrolysis of esters are well-established. Since the rate of the reaction is determined largely by the rate of addition of hydroxide ion to the carbonyl group of the ester, any substituent which withdraws electrons from the carbonyl group will increase the reactivity of the ester. The most accessible quantitative measure of the effect is the Hammett or Taft reaction constant, and a large number of measurements are available. Taft et al.2i0 found p = 2.53 for the base-catalyzed methanolysis of meta- and para-substituted (/)-menthyl benzoates, closely similar to the known value of p = 2.37 for the alkaline hydrolysis of substituted ethyl benzoates. Jones and Sloane s value239, obtained with five esters, of p = 2.41 for the methoxyl exchange reaction of substituted methyl benzoates in methanol, is almost identical. 

Steric effects on the alkaline hydrolysis of esters were taken by Taft152 to be much the same as for acid-catalyzed hydrolysis, since the transition states differ by the presence or absence of just two protons, viz. 

Solvent effects on the alkaline hydrolysis of esters have been studied systematically by a number of authors. The addition of a less polar solvent to an aqueous medium generally has a marked negative effect on the rate of hydrolysis258-260, as may be discerned from an examination of the data given in Table 31 for reactions in different solvents. Some data collected specifically for the investigation of solvent effects are given in Table 35. 

RATE COEFFICIENTS (l mole", SeC"1) FOR THE ALKALINE HYDROLYSIS OF ESTERS IN VARIOUS SOLVENTS AT 25°C A. Hydrolysis of ethyl haloacetates in aqueous ethanol (ref. 260)... 

The fate of this tetrahedral intermediate is dependent upon the nature of the substituents R and X and upon the incoming nucleophile. If X is a better leaving group than Nu, the overall reaction is a nucleophilic substitution of X by Nu, with the resultant loss of X (Fig. 3-2). This is the mechanism which is typically adopted in the alkaline hydrolysis of esters. 

Interest in the kinetics of alkaline hydrolysis of esters in DMSO + water mixtures was stimulated by the observation that the rate constant often increased gradually as x2 increased. This is observed, for example, in the alkaline hydrolysis of ethyl acetate. For higher esters, e.g. ethyl p-nitrobenzoate, the rate constant drops slightly at low x2 but then rises again until k/k x2 = 0) > 1 (Tommila, 1964). The rate of alkaline hydrolysis of esters of benzoic acid is accelerated when DMSO is added (Tommila and Palenius, 1963), as also is the rate of alkaline hydrolysis of 2,4-dinitrofluorobenzene. In the latter case the effect is less dramatic because the rate constant for spontaneous hydrolysis also increases (Murto and Hiiro, 1964). The rate constants also increase when DMSO is added to aqueous solution for reactions between hydroxide ions and benzyl chloride (Tommila... 

The alkaline hydrolysis of esters to give carboxylate salts is known as saponification, because it is the process used to make soap. Traditionally, beef tallow (the tristearate ester of glycerol—stearic acid is octadecanoic acid, C17H35CO2H) was hydrolysed with sodium hydroxide to give sodium stearate, Cj HssCC Na, the principal component of soap. Finer soaps are made from palm oil... 

The unsaturated ester 1,5-oxazocine 455 was obtained by treatment of bridged oxazocine 417d with triethyl phospho-noacetate (59% yield). Catalytic hydrogenation of455 afforded the saturated ester 456 in 77% yield. Alkaline hydrolysis of ester moiety of 1,5-oxazocine 457 gave the corresponding acid 458 in 85% yield (Scheme 89) <2004CPB675>. 

A synthesis of 4-hydroxy-substituted TIQ has been developed in connection with plant isoquinolines (169,170), and the glycine ester route used for a similar purpose (171) is shown in Fig. 23. Reaction of the benzyl bromide 85 with N-methylglycine ester gave 86 the ketoester 87 was obtained on Dieckmann condensation. Alkaline hydrolysis of ester 87 followed by treatment with mineral acid gave ketone 88 alcohol 89 was obtained on reduction of 88 with sodium borohydride. 

That a single solvent molecule clustered to a nucleophile can drastically change the reaction pathway has been demonstrated by studying the reaction of phenyl acetate with methoxide ion in the gas phase [671, 672]. Alkaline hydrolysis of esters in solution is known to proceed by attack of the nucleophile at the carbonyl carbon atom to form a tetrahedral intermediate, followed by cleavage of the acyl-oxygen bond (Bac2 mechanism) cf. Eq. (5-138a). 

The relative ability of substituents in an aromatic ring to donate or withdraw electrons is indicated qualitatively by Hammett substituent constants. It was observed that a plot of the logarithms of the rate constants (k) for the alkaline hydrolysis of esters of benzoic acid against the values of the corresponding acids, XC H4C02H, was linear, Le. 

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