Spiro heterocyclization of 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitriles to 3H-pyrrole derivatives, 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

Abstract

4-Aryl-3-methyl-4-oxobutane-1,1,2,2-tetracarbonitriles reacted with morpholine to give 8-amino-3aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles. Ar = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c). 4-Oxoalkane-1,1,2,2-tetracarbonitriles are extensively studied representatives of the series of polynitrile compounds. Derivatives of 4-oxoalkane-1,1,2,2tetracarbonitriles are known as potential antitumor agents [1] and coordination polymers with interesting topology [2]. We now perform extensive studies on the transformations of 4-oxoalkane-1,1,2,2-tetracarbonitriles by the action of nitrogen-centered nucleophiles [3]. 4-Oxoalkane-1,1,2,2-tetracarbonitriles were reported to react with ammonia and amines to form 3-amino-7oxo-4,6-diazabicyclo[3.2.1]oct-2-ene-1,2-dicarbonitriles [4], 3-amidinio-2-aminopyridine-4-carboxylates [5], diethylammonium 3,4-dicyano-5,6,7,8-tetrahydroquinolin-2-olates [6], and ammonium 4-aryl-4oxo-1,1,2-tricyanobut-2-en-1-ides [7]. We recently showed that the reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles with morpholine leads to 5-amino-2(morpholin-4-yl)-3H-pyrrole-3,4-dicarbonitriles [8, 9] and found that nitrogen-centered nucleophiles preferably add to the β-cyano groups of polyelectrophilic tetranitriles. The resulting compounds are representatives of a poorly explored class of aza heterocycles, 3H-pyrroles, which may be regarded as nitrogen-containing cyclopentadiene analogs. Despite limited published data, some 3H-pyrroles were found to exhibit antimicrobial and antitumor activity [10–12]. With a view to synthesize new functionally substituted 3H-pyrrole derivatives, we extended the series of 4-oxoalkane-1,1,2,2-tetracarbonitrile substrates and examined their reaction with morpholine in more detail. The reactions of 4-aryl-3-methyl-4-oxobutane-1,1,2,2DOI: 10.1134/S1070428013060110