N-acylimidazoles, hydrolysis

The imidazole-catalyzed isomerization of penicillin into penidllenic acids probably involves initial nucleophilic attack of imidazole on penicillin. Imidazole-catalyzed N-acylimidazole hydrolysis was used by Charton in obtaining a values (see Section III,I). 

Table 1—2. Relative rates for aminolysis and neutral hydrolysis of N-acylimidazoles [ 10-3 M solutions, 25 °C].[14]...

Mechanisms of Hydrolysis of N-Acylimidazoles and N-Acyl-benzimidazoles, Ace. Chem. Res. 26, 325 (1993). 

T.H. Fife, Kinetic and Mechanistic Effects of Ease of C-N-hond Breaking in Amide Hydrolysis, The Mechanisms of Hydrolysis of N-Acylimidazoles and N-Acyl-benzimidazoles, Acc. Chem. Res. 26, 325 (1993). 

Another interesting application of a three-phase approach to identifying N-acylimidazole as the intermediate in the imidazole-catalyzed hydrolysis... 

Efficiencies of vinyl polymers containing imidazole catalysts can be increased by enhanced apolar binding between substrate and either the catalyst s apolar polymer backbone, a specific apolar group incorporated for the purposes of enhanced binding, or a long-chain N-acylimidazole intermediate of the hydrolysis reaction. 

Water soluble, hydrophobic terpolymers of 4(5)-vinylimidazole were prepared in order to investigate hydrophobic effects attributed to random, covalently bound pendant apolar side chains in the hydrolysis of the charged apolar ester substrates (S ). The rationale for the preparation of these terpolymers is provided in the analogy to the poly[4(5)-vinylimidazole] catalysts. The apolar nature of the catalyst poly[4(5)-vinylimidazole] is derived from its hydrocarbon backbone and formation of the transient and hydrophobic N-acylimidazole intermediate. Accumulation of long-chain acylated imidazole residues, which increases hydrolysis rates dramatically, inspired the concept of utilizing hydrophobic polymer side chains. 

Most of the reactions and properties of 1-substituted imidazoles have been discussed earlier in this review. Apart from the utilization of the readily removable benzyl substituent in synthetic procedures leading to 2-substituted imidazoles, perhaps the mostexciting advances have stemmed from the reactions of the 1 -acylimidazoles (imidazolides) which are extremely reactive in such nucleophilic reactions as hydrolysis and alcoholysis.12 The use of such compounds as N,N -carbonyl-diimidazole in peptide synthesis is now commonplace. The silicon-nitrogen bond in N-trimethylsilylimidazoles is also extremely reactive, so reactive that it is attacked by a-halogenocarboxylic esters.361... 

Amino-l,2,4-oxadiazolcs (11) arc excellent sources of amidines. When they are treated with 1,3-dicarbonyl derivatives they are converted into enaminones (12), which cyclize to imidtizolcs in the presence of bases (Scheme 2.2.5). This reaction utilizes the well-known general attack of a nucleophilic group in the side chain at N-2 of the oxadiazole ring. Yields of 2-acylamino-4-acylimidazoles usually lie between 60 and 80% [21]. The free amino derivatives are readily isolated after acid hydrolysis. 

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... 

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