Acetylation, general base catalysis

Intramolecular general base catalysis of hycholysis (21a) was unexpected since the ester has a phenolic leaving group. Felton and Bruice (1968, 1969) reasoned that, if nucleophilic attack occurred, the leaving phenolate ion group would be properly positioned to attack the intermediate acylimidazole and thereby reverse the reaction. The normally less efficient general base reaction then becomes the favoured pathway, as in hydrolysis of acetyl salicylate (see Section 4). Likewise, Fife and McMahon (1970) explained bimolecular general base catalysis by imidazole (21b) in hydrolysis of o-(4-nitrophenylene) carbonate 3 49) by reversibility... 

Nucleophilic and general base catalysis of the hydrolysis of acetic anhydrides are closely related. The hydrolysis of acetic anhydride is catalysed by formate and nitrite ions by nucleophilic catalysts296. Evidence for the postulated intermediate in the latter case, acetyl nitrite, has been obtained by the addition of a-naphthylamine to the system, trapping the intermediate to form 4-amino-1,1-azonaphthalene, viz. 

Somewhat similar effects are seen in the copper(II)-promoted hydrolysis of O-acetyl-2-pyridinecarboxaldoxime (47) (equation 20).215 In this case, water attack and hydroxide ion attack are accelerated by 1.1x10 and 2.2 xlO7 times respectively. Detailed analysis indicates that Cuu-bound water or hydroxide reacts with the carbonyl carbon of the ester as shown in (48). Promotion includes contributions from increases in the effective nucleophile concentration in addition to an enhancement in the leaving group ability. General base catalysis in the attack of coordinated water is also observed. 

Considerable effort has been applied to studies of ester hydrolysis catalyzed by imidazoles (76MI40700, 80AHC(27)241). Certainly, 1-acetylimidazole can be made enzymically, probably by the sequence acetyl phosphate + coenzyme A acetylcoenzyme A+phosphate, acetyl-coenzyme A + imidazole l-acetylimidazole+coenzyme A. In addition, the imidazolyl group of histidine appears to be implicated in the mode of action of such hydrolytic enzymes as trypsin and chymotrypsin, thereby engendering further interest in the process of imidazole catalysis. The two pathways which have been found to be involved are general base catalysis and nucleophilic catalysis. In the former (Scheme 26) a basic imidazole molecule can activate a water molecule to attack the ester at the carbonyl carbon, this being followed by the usual sequence of steps as in simple hydroxide ion hydrolysis. At high imidazole concentrations the imidazole molecules may be involved directly. 

For the intramolecular catalysis in the aminolysis of N-acetyl-imidazole by diamines [68, 69] the catalytic group is in the same molecule as the nucleophile, and the problem of distinguishing between nucleophilic and general base catalysis does not arise. The rate law for the aminolysis of N-acetylimidazole by monoamines has both terms of first and of second order in amine, but in the aminolysis by ethylene diamine the term which is first order in amine is relatively more important. The rate constant for this reaction is 186 times greater than that for a monoamine of comparable basicity and a similar rate enhancement is found for the reaction with 1,3-diaminopropane. Rather smaller rate enhancements are found with 1,4-diaminobutane and 1,5-diaminopentane (see Table 4). Intramolecular catalysis is also found in the aminolysis of methyl formate... 

Fox, J.P., Jencks, W.P. General acid and general base catalysis of the methoxyami-nolysis of 1-acetyl-1,2,4-triazole. J. Am. Chem. Soc. 1974, 96(5), 1436-1449 and references cited therein. 

Fox, J.P., Jencks, W.P. General acid and general base catalysis of the methoxyami-nolysis of 1-acetyl-l,2,4-triazole. J. Am. Chem. Soc. 1974, 96(5), 1436-1449. Bruice, T.C., Donzel, A., Huffman, R.W., Butler, A.R. Aminolysis of phenyl acetates in aqueous solutions. VII. Observations on the influence of salts, amine structure, and base strength. J. Am. Chem. Soc. 1967, 89(9), 2106-2121. Williams, A., Jencks, W.P. Acid and base catalysis of urea synthesis nonlinear Bronsted plots consistent with a diffusion-controlled proton-transfer mechanism and the reactions of imidazole and N-methylimidazole with cyanic acid. J. Chem. Soc. Perkin Trans. 2. 1974, 1760-1768. 

The rate constant /ct, determined by means of Eq. (6-47) or (6-48), may describe either general base or nucleophilic catalysis. To distinguish between these possibilities requires additional information. For example, in Section 3.3, we described a kinetic model for the N-methylimidazole-catalyzed acetylation of alcohols and experimental designs for the measurement of catalytic rate constants. These are summarized in Scheme XVIIl of Section 3.3, which we present here in slightly different form. 

The reaction of acylimidazoles with imidazole is subject to both imidazole and imidazolium ion catalysis (Fife, 1965). The latter reaction is no doubt due to the imidazole-catalyzed hydration of acetylimidazolium ion, as in 18, and fully analogous to the N-methylimidazole-catalyzed hydrolysis of N-acetyl,N -methylimidazolium ion. The mechanism of the former reaction is undefined at the present time, since no 0 exchange studies have been performed with acylimidazoles in more alkaline solution where imidazole catalysis occurs. The leaving group, the imidazole anion, is quite basic (piC = 14-5) therefore it is possible that general base-catalyzed decomposition of the neutral tetrahedral intermediate (24) or general acid-assisted decomposition of the anionic tetrahedral intermediate (25) may occur. The general base-catalyzed alkaline hydrolysis of amides most probably occurs by the... 

Fig. 8-7 Bronsted plot for general acid catalysis of the acetyl transfer reaction of S-acetyl-mercaptoethylamine at 50"" and ionic strength 1.0 M, based on a value of =6.5 x 10 M" sec L (Adapted from R. E. Barnett and W. P. Jencks, J, Am. Chem. Soc. 91, 2358 (1969), Fig. 5. Copyright 1969 by the American Chemical Society. Reproduced by permission of the copyright owner.)...

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