TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 7873–7875 Pergamon Mn(OAc) 3 ·2H 2 O-mediated three-component, one-pot, condensation reaction: an efficient synthesis of 4-aryl-substituted 3,4-dihydropyrimidin-2-ones K. Ananda Kumar, M. Kasthuraiah, C. Suresh Reddy* and C. Devendranath Reddy Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India Received 13 July 2001; revised 10 August 2001; accepted 24 August 2001 Abstract—4-Aryl-substituted 3,4-dihydropyrimidin-2-ones are synthesized in high yields by one-pot cyclocondensation reactions of aldehydes, -ketoesters and urea using a catalytic amount of manganese acetate in refluxing acetonitrile. © 2001 Elsevier Science Ltd. All rights reserved. Over the past decade, dihydropyrimidinones (DHPMs), an important class of compounds, 1–9 have become increasingly significant due to their therapeutic and pharmacological properties. 1 They have emerged as integral backbones of several calcium channel blockers, antihypertensive agents and alpha-la-antagonists. 2 Syn- thetic strategies for the synthesis of the dihydropyrim- idinone nucleus involve both one-pot and multi-step approaches. Furthermore, several marine alkaloids with interesting biological activities containing the dihy- dropyrimidine-5-carboxylate core unit have recently been isolated. 3 Most notably among these are the batzelladine alkaloids, which were found to be potent HIV gp-120-CD4 inhibitors. 4 At present, several general methods for the preparation of dihydropyrimidinones are known, 1b,5–8 including var- ious solid-phase modifications suitable for combinato- rial chemistry. 9 The most simple and straightforward procedure, first reported by P. Biginelli in 1893, involves the one-pot condensation of a -ketoester with an aldehyde and urea under strongly acidic conditions, but often suffers from low yields, particularly for sub- stituted aromatic aldehydes. 1,5,6 Several modifications and improvements have been sought. Although high yields can be achieved by the following complex multi- step procedures, these methods lack the simplicity of the original, one-pot, Biginelli protocol. 9a,10 The recently reported BF 3 ·OEt 2 or polyphosphate ester- mediated Biginelli reactions 11 require long reaction times (18 h) to achieve moderate to high yields of the products. More recently, KSF 12 has also been employed for this transformation but involves a longer reaction time (10–48 h) to obtain good yields. In spite of their potential utility, some of the reported methods suffer from drawbacks such as long reaction times, low yields and cumbersome product-isolation procedures. In this communication, we describe a simple but effec- tive modification of the Biginelli reaction that produces high yields of the desired dihydropyrimidines while preserving the original one-pot strategy. The reaction of benzaldehyde, ethyl acetoacetate and urea in the pres- ence of a catalytic amount of manganese(III) acetate in refluxing acetonitrile resulted in the formation of dihy- dropyrimidinone in 96% yield (Scheme 1). Scheme 1. Keywords : Biginelli reaction; aldehydes; -ketoester; pyrimidinones. * Corresponding author. E-mail: csureshsvu@yahoo.com 0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(01)01603-3