Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

Abstract

SummaryA one-pot three-component synthesis of dihydropyrimidinones via a molecular iodine-catalyzed tandem reaction of simple readily available mono-substituted urea, alkylaldehyde, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give highly diverse dihydropyrimidinones in reasonable yields under mild reaction conditions. Moreover, the first catalytic enantioselective version of this reaction was also realized by using chiral spirocyclic SPINOL-phosphoric acids.

Green High-Yielding One-Pot Approach to Biginelli Reaction under Catalyst-Free and Solvent-Free Ball Milling Conditions

“…Several improvements were made towards good reaction conditions, and they involved the use of catalysts/reagents, transition metal-based reagents, ionic liquids, polymer-immobilized reagents, microwaves, and ultrasound irradiation; these improvements have been recently reported for the synthesis of the aforementioned compounds [20][21][22][23][24][25][26][27][28][29][30][31][32][33].…”

Photo-Oxidation Coupled Kabachnik–Fields and Bigenelli Reactions for Direct Conversion of Benzyl alcohols to α-Aminophosphonates and Dihydropyrimidones

“…Notably, 1,4-dihydropyrimidones are also a well known class of biologically active compounds with a range of therapeutic properties. 16 The traditional synthesis of dihydropyrimidones involves use of an aldehyde, a β-keto ester or β-diketone, and urea, 17 with most of the advances involving use of a Brønsted acid 18 or base, 19 metal based Lewis acids, 20 organocatalysts, 21 and heterogeneous catalysts. [22][23][24][25] In this regard, photochemical reactions are undoubtedly greener alternatives to thermal processes, shifting the synthetic path of reaction from its solvo-thermal form to a neat and photochemical form; this has become a major step towards ecofriendly synthetic methodologies.…”

A Bifunctional Metal/Acid Catalyst for One-pot Multistep Synthesis of Pharmaceuticals

“…To date, several improved reaction protocols have been reported for the synthesis of basic DHPMs which include, the direct modification of the classical one-pot Biginelli approach itself, the implementation of novel, but more complex synthetic strategies, the benefits of using microwave heating, the use of a solid-phase method, alternative green solvents or even the nonuse of solvent, etc [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. In this context, the use of reagents and catalysts supported on solid supports has received much attention in recent years because of the obvious simplification of the purification processes together with a drastic decrease in the production of waste and environmental impact [28][29][30][31].…”