Microwave‐Assisted Solvent‐Free Synthesis of Bis(dihydropyrimidinone)benzenes and Evaluation of their Cytotoxic Activity

Abstract

An effective one-pot synthesis of bis(dihydropyrimidinonoe)benzenes using chlorotrimethylsilane (TMSCl) through Biginelli condensation reaction of terephthalic aldehyde, 1,3-dicarbonyl compounds and (thio)urea or guanidine under microwave irradiation conditions is described. Excellent yields of the products and simple work-up are attractive features of this green protocol. Then, the cytotoxic activities of these compounds were evaluated on five different human cancerous cell lines (Raji, HeLa, LS-180, SKOV-3 and MCF7). Their cytotoxic study indicated that they possessed a weak to moderate activity. Furthermore, the higher activity of compound 4b bearing sulfur in C 2 position of pyrimidinone ring showed the importance of this site for cytotoxic activity of these compounds.Key words: Biginelli reaction, cytotoxicity, dihyropyrimidinone, microwave irradiation, multicomponent, terephthalic aldehyde, TMSCl Multicomponent reactions (MCRs) can be distinguished from classical, sequential two-component chemistry synthesis processes in that they use three or more chemical starting materials as the input for product formation. Up to seven starting components have been used, and MCRs have often been shown to produce higher product yields than classical chemistry (1-3).Multicomponent reactions are finding increasing use in the discovery process of new drugs and agrochemicals (4-6) and offer significant advantages over conventional linear-type syntheses. MCR condensations involve three or more compounds reacting in a single one-pot reaction, but consecutively to form a new product, which contains the essential parts of all the starting materials. The search and discovery for new MCR's on one hand (7), and the full exploitation of already known multicomponent reactions on the other hand, is therefore of considerable current interest. One such MCR that belongs in the latter category is the venerable Biginelli dihydropyrimidine synthesis. A few years ago, Pietro Biginelli reported on the one-pot cyclocondensation reaction of an aldehyde, a b-ketoester, and urea (or thiourea), a procedure known as the Biginelli reaction, is receiving increased attention. More than a century ago, Biginelli intuitively anticipated the synthetic potential of multicomponent reactions by combining in a single flask the reactants of two different reactions having one component in common (8). The result of the three-component reaction was a new product that was correctly characterized as a substituted 3,4-dihydropyrimidine-2(1H)-one (DHPM).3,4-Dihydropyrimidinones (DHPMs) constitute a very important class of organic compounds because of their attractive pharmacological properties, including antiviral, antitumour, antibacterial activities [For a review, see (9); references cited therein (10)].

Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones

“…Table 1 It is interesting to note that some of the compounds in the series are more potent than monastrol, the parent structure and the dimer 9a is almost 3 times more potent than monastrol against MCF cell line. During the completion of this present investigation, bis(dihydropyrimidinone)benzenes have been reported to possess weak to moderate cytotoxic potency [14].…”

Synthesis and anticancer evaluation of novel acenaphtho [1,2-e]-1,2,4- triazine derivatives

“…acenaphthaquinone with nucleophiles, organic and inorganic reagents have been reviewed elsewhere [19]. In the continuation of our program to develop the chemistry of potentially bioactive heterocyclic compounds and in connection with our ongoing interests in this field [20][21][22], we represent a facile procedure for the synthesis of 9-(phenyl imino hydrazin)-acenaphtho[1,2-e]-1,2,4-triazine derivatives (8a-h) via four step condensation of thiosemicarbazide and acenaphtylene -9,10 Quinone to form acenaphtho [1,2-e]-1,2,4-triazine-9(8H)-thiones and subsequent reaction with benzyl chloride derivatives. The prepared compound was subjected to the other reaction with hydrazine and, then, with different benzaldehyde derivatives for achieving the final products.…”

Solvent free one pot synthesis of novel naphtho[1,8-gh] quinazoline-7,10-dione derivatives with CuCl2

“…In connection with our ongoing work on multi-component condensations (MCCs) [27,28] and an our interest to metal catalyzed reactions, we now wish to report a facile and rapid one-pot solvent free three component procedure preparation of DHPs derivatives with CuCl 2 as an nontoxic, inexpensive and easily available reagent, under solvent-free condition at the range of temperatures.…”