New environmentally benign protocol for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones: Practical access to mitotic kinesin EG5 inhibitor Monastrol

Abstract

A simple, efficient, and cost-effective method has been developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by a one-pot three component cyclocondensation reaction of 1,3 dicarbonyl compound, aldehyde, and urea using benzyltriethylammonium chloride as the catalyst, under solvent-free conditions: the scope of this protocol is utilized for the synthesis of mitotic Kinesin EG5 inhibitor monastrol.

Recent developments in solvent-free multicomponent reactions: a perfect synergy for eco-compatible organic synthesis

“…293 A simple, efficient, green, and cost-effective procedure for the synthesis of dihydropyrimidinones 339 has been developed by Ranu et al 294 via the coupling of 337, 338, and 140/215 under solvent and catalyst-free conditions (Scheme 98D). Bose and co-workers 295 have developed a simple, efficient, and cost-effective method for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones 339 via the onepot three-component cyclocondensation of 337, 338, and 140/215 using benzyltriethylammonium chloride as the catalyst under solvent-free conditions (Scheme 98E). A synthetic procedure for the preparation of 3,4-dihydropyrimidin-2-(1H)-ones/thiones 339 from 337, 338, and 140/215 in the presence of a catalytic amount of silica-supported P 2 O 5 (P 2 O 5 /SiO 2 ) at 85 uC has been given by Hasaninejad et al 296 in high yields (Scheme 98F).…”

Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products

“…According to the literature data, the participation of 2hydroxybenzaldehyde (salicylaldehyde) or different substituted 2-hydroxybenzaldehyde derivatives, methylene active compound and urea or thiourea under Biginelli reaction conditions [85][86][87][88][89][90][91][92][93][94][95][96][97] leads to the formation of oxygen-bridged tricyclic pyrimidine derivative B instead of simple dihydropyrimidine A (Scheme 2).…”

“…As a result, the steric effect determines the selectivity of the Biginelli reaction in the presence of copper triate towards product A. Another factor that supports this idea is the analysis of literature, [85][86][87][88][89][90][91][92][93][94][95][96][97] according to which the formation of oxygen-bridged tricyclic pyrimidine derivative B in the one-step one-pot process occurs in the presence of Arrhenius acids (H + ), which small size facilitates the formation of oxygenbridged tricyclic compound B.…”

Facile Ecofriendly Synthesis of Monastrol and Its Structural Isomers via Biginelli Reaction

“…Our research group has been long involved in developing green chemical methodologies for the organic synthesis, so our attention was attracted by the reported methods for performing the Biginelli reaction avoiding the use of harmful solvents and/or employing nonconventional technologies. − From this point of view, the use of microwave activation to perform the Biginelli reaction in a few minutes,and the adoption of environmental friendly systems such as a nontoxic recyclable catalyst under solvent-free conditions, , were particularly attractive. Along this line, it is worth noting that several groups have developed solvent-free syntheses of Monastrol and other dihydropyrimidine derivatives. ,,− Liu and Wang reported the first solvent- and catalyst-free Biginelli reaction applied to the synthesis of dihydropyrimidines. Significantly, they highlighted the difficulties in using hydroxylbenzaldehyde when Lewis acids were used as catalysts, so they proposed that a catalyst-free method could avoid this shortcoming even though the yields obtained were lower than those observed in the presence of a catalyst and solvent.…”