Highly efficient three-component synthesis of 1H-indazolo[1,2-b]phthalazinetrione derivatives cataly.pdf

ORIGINAL PAPER Highly efficient three-component synthesis of 1H- indazolo[1,2-b]phthalazinetrione derivatives catalyzed by heteropolyacids Hong-Juan Wang ? Xiao-Nan Zhang ? Zhan-Hui Zhang Received: 27 November 2009 / Accepted: 23 February 2010 / Published online: 27 March 2010  Springer-Verlag 2010 Abstract Efficient one-pot condensation of aldehyde, dimedone, and phthalhydrazide has been achieved in the presence of a catalytic amount of tungstosilicic acid under solvent-free conditions. A variety of 1H-indazolo- [1,2-b]phthalazinetrione derivatives were prepared in high to excellent yields in short time. Keywords Multicomponent reaction  1H-indazolo[1,2-b]phthalazinetrione  Aldehyde  Phthalhydrazide  Heteropolyacid  Solvent-free conditions Introduction Heterocycles containing the phthalazine ring are important targets in synthetic and medicinal chemistry, because this fragment is a key moiety in numerous biologically active compounds [1, 2]. Phthalazine derivatives, which have two bridgehead nitrogen atoms in a fused ring system, possess cytotoxic [3], antimicrobial [4], anticonvulsant [5], anti- fungal [6], anticancer [7], and anti-inflammatory [8] activities. Phthalazine-containing compounds are also highly potent inhibitors of vascular endothelial growth factor receptor II (VEGFR-2) [9–11]. Moreover, these compounds exhibited good promise as new luminescence materials or fluorescence probes [12]. In view of their great importance, several methods have been reported for syn- thesis of phthalazine derivatives, including the reaction of phthalhydrazide, aromatic aldehydes, and malononitrile [13, 14], the reaction of phthalhydrazide and dialkyl acet- ylenedicarboxylates in the presence of N-heterocycles [15], and palladium-catalyzed 1,3-dipolar cycloaddition of methylenecyclopropanes, vinylidenecyclopropane, and methylenecyclobutane with phthalhydrazide [16]. How- ever, most of the reported procedures describe synthesis of only a narrow range of phthalazines.