654 International Journal of Drug Design and Discovery Volume 2 • Issue 4 • October – December 2011 Synthesis, Characterization and Biological Activity of Novel N-p-methylbenzoyl-N’ substituted thiourea Amit Semwal 1 *, Amit Nigam 2 , D.C.P Singh 3 1 Gyani Inder Singh Institute of Professional Studies, Dehradun, Uttarakhand, India. 2 Hygia Insitute of Pharmaceutical Education & Research, Lucknow, UP, India. 3 Institute of Foreign Trade & Management, Moradabad, UP, India. ABSTRACT: A series of N-p-methylbenzoyl-N’ thiourea derivatives bearing different substituents have been synthesized and screened in order to evaluate for their antibacterial and antifungal activity. Antibacterial and antifungal activity of the title compounds has been evaluated by varying the substituents in the thiourea moiety. Reaction of p- methylbenzoyl chloride with ammonium thiocynate followed by the addition of various aromatic amines afforded N-p- methylbenzoyl-N’ substituted thiourea. The structures of newly synthesized compounds has been supported by IR and 1 HNMR spectral analysis. Among the synthesized compounds N-(4-methylbenzoyl)-N’-(4-chloro-2-nitrophenyl) thiourea and N- (4-methylbenzoyl)-N’-(4-methylphenyl) thiourea have been found to exhibit excellent antibacterial and antifungal activity when compared with the standard drug. KEYWORDS: Thiourea; aromatic amine; antibacterial activity; antifungal activity. Introduction A heterocyclic compound is one which possesses a cyclic structure with at least two different kinds of hetero atoms in the ring. Nitrogen, oxygen, and sulphur are the most common heteroatoms. Heterocyclic compounds are very widely distributed in nature and are essential to life in various ways 1,2 . The six and five membered heterocyclic compounds containing sulphur and nitrogen have maximum attention, as they have many biological and industrial application 3-5 . During recent years there has been intense investigation of different classes of thiourea compounds, many of which were found to be pharmacologically active like anticancer 6,7 , hypnotic, antifungal 8,9 , antibacterial 10 , diuretic 11 , antiviral, anti-tubercular, anti-thyroidal, herbicidal and insecticidal activities 12 organocatalyst 13 , and as agrochemicals 14,15 . In this communication, results of synthesis, spectroscopic studies and antimicrobial activity of N-p-methylbenzoyl-N’ substituted thiourea derivatives are presented. Materials and Methods Melting points of the synthesized compounds were determined by open capillary method and are uncorrected. Thin layer chromatography was performed on pre-coated silica gel G 254 plates and visualized in iodine or UV. The IR spectra of synthesized compounds were recorded in potassium bromide discs on Schimadzu FTIR Spectrophotometer 8300. The 1 H NMR spectra of the synthesized compounds were recorded in DMSO and CDCl 3 using AV-300 Broke Jeol Spectrophometer. Synthesis of p-methylbenzoylchloride 13.6 g of p-toluic acid was transferred into 250 ml of two necked RBF then added 15 ml of thionyl chloride and some pieces of porcelain chips into RBF from 1 st neck and 2 nd neck was covered with stopper, at the same time the condenser was clamped with RBF and the top of condenser was capped with calcium guard tube or cotton wool and whole reaction mixture was reflux for 3-4 hours with occasional gentle shaking up to the complete evolution of gas after that cooled the flask and then fitted for distillation under reduced pressure the reaction mixture was heated at 70 o C-80 o C for the removal of excess of SOCl 2 or unreacted SOCl 2 and collected in 1 st flask after that the temperature rapidly raised to 225 o C and the distilled was collected in another flask which was final product p-toluoyl chloride. The different compounds of the series were synthesized by reaction of p-methylbenzoyl chloride (1) with ammonium thiocynate (2) followed by the addition of various aromatic amines (3) affording N-p-methylbenzoyl-N’ substituted thiourea (3a-h). International Journal of Drug Design and Discovery Volume 2 • Issue 4 • October – December 2011. 654-658 654