Synthesis of β-Nitroamines via Classical Mannich and Aza-Henry Reactions

Chemistry and pharmacological activity of various types of Mannich bases and their derivatives were well documented. A survey of the literature revealed extensive studies on the synthesis and reactivity of Mannich bases derived from ketones, amides, enamines, phenols and indoles of widely different structures, while comparatively little attention has been given to Mannich bases derived from nitroalkanes and related nitrocompounds. Mannich reactions using nitroalkanes and related compounds as substrates are of synthetic relevance and the products are promising as biologically active substances. It is known that the nitro group is an important constituent of many biologically significant heterocycles such as antibiotic drugs (nitrofurantoin and nitrofurazone). A number of nitro-heterocycles of pharmacological interest were also synthesized by Mannich reactions with suitable nitro-substrates. In view of this, and because of the widespread and increasing interest in the chemistry of Mannich bases, the present work is concerned with attempts to extend the scope of Mannich reactions with nitroalkanes to include the synthesis of a variety of nitro N- and S-heterocycles.