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Synthesis and structural analysis of novel isomeric amidino-substituted 2-aminophenols

Recently our scientific focus has been placed on amidino-substituted benzothiazole compounds with emphasis on their synthesis, study of anticancer activities and DNA binding properties [1]. In contrast to a great number of biologically active amidino-substituted benzimidazole and benzothiazole derivatives, benzoxazoles are still rare [2]. The main reason is the lack of a general method for their preparation, which could be based on a condensation reaction of the amidino- substituted 2-aminophenols with aldehydes, carboxylic acids and carboxylic acid derivatives as commercially available substrates. Most common method for amidine preparation is nucleophilic addition of amines or ammonia to suitably activated carboxylate equivalents such as imidates, thioimidates, and imidoyl chlorides. Imidates can generally be prepared either by base-catalyzed or acid- catalyzed (Pinner synthesis) addition of alcohol to nitrile. The addition of dry hydrochloric acid to a mixture of nitrile and an alcohol leads to the hydrochloride salt of an imino ester. This salt can further react with ammonia or with excess of an amine to form amidine. Here, we report efficient synthesis by Pinner reaction of unsubstituted, N-substituted and cyclic amidine derivatives starting from 2- amino-4-cyanophenole (1) and 2-amino-5- cyanophenole (2) (Figure 1). Resulting compounds were isolated in the zwitterionic form and their structures were confirmed by 1H and 13C NMR spectroscopy, LC-MS and elemental analysis. In addition, zwitterionic form of 3d is confirmed by X-ray structural analysis.

synthesis, amidines, 2-aminophenols

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