%0 Journal Article
%T Benign Methodology and Efficient Catalysis for the One-Pot Multicomponent Synthesis of Dihydropyrimidinones and Thiones: A New Key for Old Lock
%A Parvez Ali
%A Naziyanaz Pathan
%A Taibi Ben Hadda
%J Journal of Applied Chemistry
%D 2014
%R 10.1155/2014/835758
%X In the present communication, under the influence of microwaves, cuprous chloride has been demonstrated to be safe, mild, efficient, and inexpensive catalyst for the Biginelli discovered multicomponent reaction (MCR) between aromatic aldehydes, urea/substituted urea, and ethyl acetoacetate to produce structurally diverse dihydropyrimidin-2(1H)-ones (DHPMs) and thiones in an ecofriendly solvent-free protocol. The practical and simple protocol led to excellent yields of the dihydropyrimidin-2(1H)-one derivatives under mild reaction conditions and within short span of reaction times with easy reaction workup by maintaining excellent atom economy. 1. Introduction In multicomponent reactions (MCRs), three or more reactants come together in a single reaction vessel to form new products that contain portions of all the components [1¨C5]. In this dynamic era of chemistry where a premium effort is put on speed, diversity, and efficiency in the drug discovery process [6], MCR strategies offer significant advantages over conventional linear-type synthesis [1¨C5]. One such MCR that belongs to this category is the venerable Biginelli dihydropyrimidinones synthesis. In 1893, Italian chemist Pietro Biginelli reported the acid catalyzed cyclocondensation reaction of ethyl acetoacetate (1), benzaldehyde (2), and urea (3) [7]. The reaction was carried out by heating a mixture of the three components by dissolving it in ethanol with a catalytic amount of HCl at reflux temperature. The product of this novel one-pot, three-component synthesis that precipitated on cooling of the reaction mixture was identified correctly by Biginelli as 3,4-dihydropyrimidin-2(1H)-one 4 (Scheme 1) [8, 9]. Scheme 1: Traditional Biginelli reaction. Owing to their remarkable pharmacological properties such as calcium channel blockers, antitumor, and anti-inflammatory activities, dihydropyrimidinones and their derivatives have increasingly attracted the attention of synthetic chemists [10¨C15]. Moreover, the dihydropyrimidine-5-carboxylate core has been found in several marine natural products which are potent HIVgp-120-CD4 inhibitors [16, 17]. However, despite the potential utility of dihydropyrimidinones as bioactive compounds, their antifungal activities are also studied [18]. Thus, due to immense pharmacological profile of this class of compounds, research interest towards this area is growing day by day. This in turn increases the attempts to develop various versatile, safe, and quick processes for their synthesis. The classical Biginelli condensation protocol suffers from the drawbacks like
%U http://www.hindawi.com/journals/jac/2014/835758/