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

The treatment of alkyl 2-chloroacetoacetate with ethyl 3-hydrazino-3-oxopro pionate, (4-chlorobenzenesulphonyl)acetic acid hydrazide, 4-nitrophenylacet ic acid hydrazide, phenylacetic acid hydrazide, thiophene-3-acetic acid hyd razide or indole-3-acetic acid hydrazide leads to the corresponding hydrazo ne derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the c orresponding 1-aminopyrrole rings through the relevant 1,2-diaza-1,3-butadi ene intermediates. In the presence of sodium methoxide, the activated methy lene group present on the I-amino side chain of the heterocycles obtained f rom ethyl 3-hydrazino-3-oxopropionate or 4-nitrophenylacetic acid hydrazide attacks at room temperature 1,2-diaza-1,3-butadienes affording the respect ive hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise a t room temperature providing -NH-CO-CH-bridged pyrrole-pyrazole systems. In the case of (4-chlorobenzenesulphonyl)acetic acid hydrazide, the correspon ding 1-aminopyrrole does not add a further molecule of 1,2-diaza-1,3-butadi ene giving rise to 1H-pyrrole and 2-oxohydrazone derivatives as identified compounds. Under the same reaction conditions, the NH group of 1-aminopyrro les derived from phenylacetic acid hydrazide, thiophene 3-acetic acid hydra zide 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 differ ent N-bonded pyrrole-pyrazole systems. (C) 2001 Published by Elsevier Scien ce Ltd.