Conversions of 2-aminopyridines into 5-substituted derivatives mediated by 1-hydroxymethylbenzotriazole
Abstract
2-Aminopyridines are benzotriazolylmethylated at the 5-position by 1-hydroxymethylbenzotriazole. The methylene group of 2-amino-5-(benzotriazolylmethyl)pyridines 6 can be mono- or di-lithiated and subsequently substituted by various electrophiles. The benzotriazole moiety in both the primary products 6, and in their methylene-substituted derivatives 8 and 9, is displaced by alkyl and aryl anions derived from Grignard reagents, or by alkoxide and thioalkoxide anions. Moreover, the derivative 8a undergoes smooth elimination of benzotriazole under basic conditions to generate the 5-vinyl-substituted 2-aminopyridine 12. These approaches allow the synthesis of many new types of 5-substituted 2-aminopyridines.