Regioselective role of the hydrazide moiety in the formation of complex pyrrole–pyrazole systems

Abstract

The treatment of alkyl 2-chloroacetoacetate with ethyl 3-hydrazino-3-oxopropionate, (4-chlorobenzenesulphonyl)acetic acid hydrazide, 4-nitrophenylacetic acid hydrazide, phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide leads to the corresponding hydrazone derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the corresponding 1-aminopyrrole rings through the relevant 1,2-diaza-1,3-butadiene intermediates. In the presence of sodium methoxide, the activated methylene group present on the 1-amino side chain of the heterocycles obtained from ethyl 3-hydrazino-3-oxopropionate or 4-nitrophenylacetic acid hydrazide attacks at room temperature 1,2-diaza-1,3-butadienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise at room temperature providing NHCOCH-bridged pyrrole–pyrazole systems. In the case of (4-chlorobenzenesulphonyl)acetic acid hydrazide, the corresponding 1-aminopyrrole does not add a further molecule of 1,2-diaza-1,3-butadiene giving rise to 1H-pyrrole and 2-oxohydrazone derivatives as identified compounds. Under the same reaction conditions, the NH group of 1-aminopyrroles derived from phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide adds at room temperature 1,2-diaza-1,3-butadienes producing another type of hydrazonic 1,4-adduct. Under basic conditions, these adducts cyclise at room temperature giving rise to different N-bonded pyrrole–pyrazole systems.