%0 Journal Article
%T Ammonium Trifluoroacetate-Mediated Synthesis of 3,4-dihydropyrimidin-2(1H)-ones
%A Chandran Raju
%A R. Uma
%A Kalaipriya Madhaiyan
%A Radhakrishnan Sridhar
%A Seeram Ramakrishna
%J ISRN Organic Chemistry
%D 2011
%R 10.5402/2011/273136
%X A simple and economic synthesis of 3,4-dihydropyrimidin-2(1H)-ones using ammonium trifluoroacetate as catalyst and as solid support is accomplished. Easy workup procedure for the synthesis of title compounds is well arrived at and is well documented. 1. Introduction Three component coupling reactions are very efficient and simple methodology for the synthesis of dihydropyridines [1, 2] and dihydropyrimidine derivatives [3]. Biginelli compounds and their analogues have been reported to possess a wide variety of pharmaceutical and therapeutic properties [4¨C11]. Though the first report on Biginelli reaction came in the 19th century, the research on dihydropyrimidines is not fully saturated because of their biological application as antihypertensive agents and calcium channel blockers [9¨C11]. Moreover, monastrol, a dihydropyrimidine derivative, is much exploited because of its extensive application as a cell permeable small-molecule inhibitor of the mitotic kinesin, Eg5 [12]. There are many reports for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones using Lewis acid catalysts such as InCl3 [13], LaCl3¡¤7H2O [14], Yb(OTf)3 [12], Mn(OAc)3¡¤2H2O [15], Cu(OTf)2 [16], heteropolyacids [17], and so forth [18¨C30]. Phenyl boronic acid [31] was reported to catalyse the Biginelli reaction in acetonitrile solvent under refluxing conditions for 18£¿h. Ammonium chloride [32] solid-supported solvent-free synthesis of 3,4-dihydropyrimidin-2(1H)-ones at 100¡ãC is also reported. Green approach via polystyrene sulfonic acid [33] is also reported under microwave heating at 80¡ãC and via TaBr5 [34] catalyst at 75¡ãC. 2. Results and Discussion In order to overcome the strong acidic conditions, higher temperature conditions, increased reaction times, unsatisfactory yields, and complicated workup procedures, we optimized and herein we disclose a simple protocol for the synthesis of the title compounds in higher yields employing ammonium trifluoroacetate as catalyst. The role of the same as catalyst in organic synthesis is relatively less explored. The catalyst effectively imparts the acidity that catalyzes the three-component coupling at 80¡ãC in 10 to 20£¿min with good to excellent yields (Scheme 1). Scheme 1 Further ammonium trifluoroacetate is employed as solid support for 3,4-dihydropyrimidin-2(1H)-ones synthesis. The reaction mixture after completion forms the product as solid which is given water wash to get rid of the solid support. The solid was again given aqueous ethanol wash to drive off other organic impurities to obtain pure 3,4-dihydropyrimidin-2(1H)-ones in quantitative
%U http://www.hindawi.com/journals/isrn.organic.chemistry/2011/273136/