A Green and Facile Synthesis of 2-Alkylsulfanyl-3H-quinazolin-4-one

Abstract

The quinazolinone ring system forms an important class of N-heterocyclic compounds as it is present in a large number of compounds with useful biological properties such as antiinflammatory 1,2 , anticonvulsant 3 , hypotensive 4 and antimalarial 5 types. 2-Thioquinazolinones possess good analgesic activities 6 . 2-Substituted quinazolin-4(3H)-ones exhibit a wide range of pharmacological properties 7,8 , such as good antimicrobial activity against different species of gram positive bacteria 9 , gram-negative bacteria 10 , pathogenic fungi 11,12 , antitubercular activity 13,14 and antitumor chemotherapeutic agent 15,16 . EXPERIMENTALAll the reagents used in this work were obtained from commercial suppliers. Solvents were freshly distilled before being used. Melting points were determined using a Buchi melting point B-545 apparatus and are uncorrected. TLC analyses were done on glass plates coated with silica gel GF-254 and spotting was done using iodine/UV lamp. IR spectra were recorded on a Perkin-Elmer model 446 instrument in KBr phase. 1 H NMR were recorded in CDCl3/DMSO using 400 MHz Varian Gemini spectrometer and mass spectra were recorded on a LC-MS spectrometer, model HP-5989A. Experiments under microwave irradiation were carried out by using the commercially available CEM discover microwave reactor. Elemental analyses were performed by Varian 3LV analyzer series CHN analyzer.Reaction of 2-thioquinazolinone (1) with various alkylating agents like dimethyl sulphate, diethyl sulphate and benzyl chloride in the presence of K2CO3 as a mild base, by a simple physical grinding, microwave irradiation and PEG-600 under solvent-free conditions for 10-15 min at room temperature, followed by processing, gave respectively 2-methylsulfanyl-3H-quinazolin-4-one (2a, i.e., R = CH3), 2-ethylsulfanyl-3H-quinazolin-4-one (2b, i.e., R = C2H5) and 2-benzyl sulfanyl-3H-quinazolin-4-one (2c, i.e., R = PhCH2Cl). It appears from this study that green syntheses such as solid phase synthesis (physical grinding) and microwave irradiation gives better yields, quality and in less reaction time the products over conventional methods involving green solvents like ethanol, PEG-600 etc. The entire sequences of reactions have been carried out using eco-friendly solvents and green conditions.