Imidazoles quaternization rates

Pyrazoles161 and Imidazoles (see Sections VI,A, B, D, and E). Effects of A-aryl substituents on rate constants for the quaternization of pyrazoles (60)168 and imidazoles (61)169 are correlated using a Hammett equation. It is not possible to decide whether the greater sensitivity (p... 

The quaternization of 1-substituted imidazoles is a facile reaction which leads to a stable quaternary salt via an 5n2 reaction (Scheme 16) which may be affected by steric factors. It has been shown (78AHC(22)7l) that the effects of fV-aryl substituents on rate constants for the quaternization of imidazoles can be correlated using a Hammett equation. The value of p (-0.45) for the ethylation of imidazoles shows little sensitivity to substituent effects, but this is to be expected since the basic pK values of the fV-aryl compounds do not vary widely, and the rate of alkylation must depend on the basicity of the nitrogen being quaternized. Certainly the expected sequence of reactivities, 1-methyl > 1-benzyl > 1-phenyl, is observed in the ethylation of 1-substituted imidazoles with iodoethane in ethanol or acetone, and although only qualitative observations are available, l-methyl-4-and -5-chloroimidazoles react less readily than 1-methylimidazole. Considerable experimental difficulty is experienced in quaternizing nitro-substituted imidazoles. 

In the electrochemical reduction of 5-bromo-l-methyl-4-nitroimidazole some cleavage of the C—Br bond is evident giving rise to the debrominated product (79JGU1877). Imidazole itself is not reducible cathodically in aqueous media, but electrons have been attached to imidazole and histidine in aqueous solution the rate of oxidation depends on pH. Protonated or quaternized imidazoles form the neutral conjugate acids of the true anion radical, and a number of anion radicals have been made from nitroimidazoles under various radiolytic conditions (79AHC(25)205). The electrochemical reduction of 2-cyanobenzimidazole 3-oxide gives sequentially 2-cyanobenzimidazole and 2-aminomethylbenzimidazole (80ZC263). 

N-Aryl substituents usually depress the basic properties of the imidazole or benzimidazole nucleus. The effects of substituents on the aryl group are evident from the data listed in Table 7 which also lists rate constants for quaternization with iodoethane, a reaction which is dependent upon the nucleophilic character of the pyridine-type nitrogen (70CHE194). A phenyl group withdraws electrons from the imidazole ring, but does so rather weakly. The p value of +0.753 for the protonation process is in accord with weak electron transfer from the phenyl substituent to the basic nitrogen. 

Reactions of [Co(NH3)6] with pyridinyl carboxylate radicals, L, have been compared with reactions of the carboxylate-bound radical in [(NH3)5CoL f Only the species [(NH3)5Co02CCH20COC5H4N ] " decays by an intramolecular route with a first-order rate constant of 4 x 10 s , while radicals of quaternized pyridine derivatives are oxidized by [(NH3)5CoL] complexes in solution. The coordinated imidazole in [(NH3)5CoImH] traps an electron more rapidly than the cobalt(ni) center allowing detection of an intermediate in pulse-radiolysis experiments and the determination of the intramolecular electron transfer rate as 2.5 x 10 s . ... 

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