Synthesis and structural studies of novel benzothiazole derivative and evaluation of their antimicrobial activity

Benzothiazole are important group of compounds repo rt d to have various biological activities and hence the present study was undertaken in order to synthesize same new compounds built upon this nucleus with the hope to enhance the biol ogical properties of newly designed compounds. In the present work 2-substituted benzot hiazole (a) was prepared from p-tolnidine via cyclization reaction then N-2-benzothiazolyl th iourea was synthesized by reacting (a) with ammonium thiocyanate. Then its semicarbazide deriva tive was formed reacting with hydrazine hydrate in ethylene glycol which was reacted with v arious acetophenons to form respective derivatives. Chemical structure of product and thei r purity was ascertained by TLC, MP and various spectral methods as FTIR and NMR. The inhib tion of microorganism under standard condition was determined to demonstrate antimicrobi al activity of derivatives using gram positive and gram negative bacteria such as St phylococcus aureus, Pseudomonas. aeruginosa,, Escherichia coli with ampicillin as standard compounds. IR and NMR s pectral data were supporting the presence of synthesized compounds. D erivatives showed significant zone of inhibition against the both gram positive and gram negative bacteria. The metanitroacetophenone derivative showed excellent activity against P. aeruginosa. ______________________________________________________________________________ INTRODUCTION Benzothiazole and its derivatives are bicyclic ring system and have identified showing a multiple applications. From the ancient time a number of 2substituted benzatiazole derivatives were investigated and identified for their various pharm cological activities. Benzothiazole derivatives have been intensively studied for their antitumour [1-3], neurotransmission blocker [4-6], A. Pandurangan et al Der Pharma Chemica, 2010, 2 (3): 316-324 ______________________________________________________________________________ 317 www.scholarsresearchlibrary.com calmodulin (CaM) antagonists [7], neuroprotective a gent [8, 9] and other biological activities [10-14]. In view of these observations, some novel N-2-benzo thiazolylthiourea derivatives have been synthesized in order to examine their in vitro anti microbial activities against various gram positive and gram negative microorganisms in compar ison with drug ampicillin in accordance with the method described in literature. MATERIALS AND METHODS Experimental Chemicals The reagents and solvents were commercially availab le (CDH, Rankem, Merck) and of synthetic grade. Solvents and reagents were dried prior to us e over anhydrous sulfate or fused calcium chloride. Synthetic scheme The synthesis part of the present work was divided in to following 1. Synthesis of p-tolyl thiourea Para-toludine (5.35gm) was dissolved in a mixture o f conc. HCL (4.3ml) and water (11.6ml) by heating on a water bath. Cooled the contents added soli ammonium thiocyanate (3.8gm) and heated the mixture on the water bath for 22hrs. Pre cipitated product was cooled and filtered .Then washed with water and dried. Recrystallized w ith aqueous methanol gave colored crystals. Yield 4.12gm (77%), (Fig 1) CH3 NH2 Conc.Hcl,H2O NH4SCN CH3 NHCSNH2 Para-toludine Para-tolyl thiourea Fig 1: Synthesis of p-tolyl thiourea [S-1] 2. Synthesis of 2-Amino-6-methyl benzothiazole A solution of bromine (6.8ml) 0.17 mol, in CHCl 3 (50ml) was poured in to a mixture of the dry powdered Para tolyl thiourea (20 gm) 0.13mol and CH Cl3 (60ml) which was heated to boil contained in a three neck flask. Heat was evolved a nd the mixture rapidly gives a clear solution which was kept at below 30 o C by external heating. When the initial reaction su bsided the flask was fitted with a stirrer and a condenser carrying a calcium chloride tube and the mixture refluxed until the evolution of Hydrogen bromide ce as d. The hydrogen bromide derivative of 2amino-6-methyl benzothiazole kept for overnight and crystallizes out (m.p.168 o C). The cold mixture was filtered and the insoluble residue susp ended in water and treated with sodium sulphite until traces of free bromine get evolved, The mixture was again filtered and the precipitate was collected and dried. Yield 3.25 gm (65%) (Fig 2) A. Pandurangan et al Der Pharma Chemica, 2010, 2 (3): 316-324 ______________________________________________________________________________ 318 www.scholarsresearchlibrary.com CH3