In an attempt to find a new class of antimicrobial agents, a series of oxygen heterocyclic isocoumarins, dihydroisocoumarins, aromatic / aliphatic amino methyl isocoumarin derivatives having benzoyl group at 3rd position in isocoumarin moiety was synthesized using simple appropriate starting material o-acyl benzoic acid and bromoacetophenone derivatives in presence of anhy. K2CO3 in ethyl methyl ketone. These compounds were screened for their antibacterial activity against gram (+ve) S. Aureus and gram (-ve) E. Coli bacteria. Most of the isocoumarin derivatives were active against gram (+ve) bacteria and the best result was with dihydroisocoumarin.