Ionic liquids catalyzed Biginelli reaction under solvent-free conditions

3,4-Dihydropyrimidin-2(1H)-ones were synthesised in high yields by one-pot three-component Biginelli condensation in the presence of room temperature ionic liquids such as 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMImBF4) or hexafluorophosphorate (BMImPF6) as catalysts under solvent-free and neutral conditions. © 2001 Elsevier Science Ltd. All rights reserved. Recently, the interest in synthesis of 3,4-dihydropyrimidin-2(1H)-ones (denoted as Biginelli compounds) and their derivatives is increasing tremendously because of their therapeutic and pharmacological properties and also because of interesting biological activities of several marine alkaloids which contain the dihydropyrimidine nucleus. Synthetic strategies for the dihydropyrimidine nucleus involves one-pot to multistep approaches. The classical Biginelli synthesis is a one-pot condensation using -dicarbonyl compounds with aldehydes (aromatic and aliphatic aldehydes) and urea or thiourea in ethanol solution containing catalytic amounts of acid. This method, however, involves long reaction times, harsh reaction conditions and unsatisfactory yields. Improvements in such syntheses have been sought continuously. Recently, it was reported that Lewis acids (such as BF3·OEt2) in combination with transition metals and a proper proton source were effective catalysts for this reaction. Dihydropyrimidines were also synthesized in high yields by one-pot cyclocondensation of aldehydes, acetoacetates and urea using various acid catalysts like Amberlyst-15, NafionH, KSF clay and dry acetic acid under microwave irradiation. More recently, lanthanide triflate, lanthanum chloride, ferric chloride hexahydrate, and indium chloride as catalysts for the one-pot syntheses of dihydropyrimidinones were also reported. On the other hand, because of the great potential of room temperature ionic liquids as environmentally benign media for catalytic processes, much attention has currently been focused on organic reactions catalyzed by ionic liquids, several organic reactions catalyzed by ionic liquids have been reported with high performance. This offered some new clues that using ionic liquids as catalysts for those traditionally acid–base synthetic reactions may not only be possible but also practical and even highly efficient. Our new approach reported herein involves the use of room temperature ionic liquids based on 1-n-butyl-3methylimidazolium tetrafluoroborate (BMImBF4) or hexafluorophosphorate (BMImPF6) as catalysts for the Biginelli condensation reaction under solvent-free conditions.