A series of thiophene derivatives was synthesized with an objective to develop novel and potent antimicrobial agents of synthetic origin. The required starting material ethyl-2-amino-4,5,6,7- tetrahydro-1-benzothiophene-3-carboxylate(1) was synthesized via a multicomponent condensation between sulphur, cyclohexanone and ethylcyanoacetate adopting Gewald Reaction. The Compound 1 was reacted with various substituted aldehydes to synthesize Schiff bases which on cyclization with thioglycollic acid in catalytic amount of ZnCl2 yielded the final products (R1-R9). Synthesized compounds were purified, characterized and evaluated for their antimicrobial activity. Most of the compounds exhibited moderate to significant activities.