Regioselective role of the hydrazide moiety in the formation of complex pyrrole±pyrazole systems Orazio A. Attanasi, Paolino Filippone, p Francesca R. Perrulli and Stefania Santeusanio Istituto di Chimica Organica, Universita Á di Urbino, Piazza della Repubblica 13, 61029 Urbino, Italy Received 21 July 2000; revised 8 November 2000; accepted 23 November 2000 Abstract ÐThe 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-buta- dienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise at room temperature providing ZNHZCOZCH-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 identi®ed 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. q 2001 Published by Elsevier Science Ltd. 1. Introduction The synthetic usefulness of 1,2-diaza-1,3-butadienes as building blocks in organic chemistry has been well docu- mented. 1±6 In a previous preliminary paper, we reported the sequential construction of widely functionalized pyrrole± pyrrole or pyrrole±pyrazole systems from conjugated azoalkenes. 7 In that report, we described an easy protocol Tetrahedron 57 (2001) 1387±1394 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Published by Elsevier Science Ltd. PII: S0040-4020(00)01125-X Keywords: hydrazides; hydrazones; 1,2-diaza-1,3-butadienes; pyrroles; pyrazoles. p Corresponding author. Fax: 139-0722-2907; e-mail: attanasi@uniurb.it Scheme 1.