Improved method for microwave-assisted synthesis of benzodiazepine-2,5-diones from isatoic anhydrides mediated by glacial acetic acid

Abstract

An improved and simpler method for the synthesis of benzodiazepin-2,5-diones and 7-iodobenzodiazepin-2,5-diones catalyzed by glacial acetic acid using isatoic anhydride and 6-iodoisatoic anhydride, respectively, as starting materials is reported. The target products were achieved in good yields (up to 71%) using microwave irradiation as the activating mode of reaction in the presence of acetic acid instead of the traditional polar aprotic solvents as dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or dimethylacetamide (DMAC). Moreover, relatively simple purification workup is required. The optimal temperature to obtain the benzodiazepin-2,5-dione derivatives was 130 °C, while the best irradiation time was 3 min. In addition, the methodology for the selective preparation of 6-iodoisatoic anhydride with an overall yield of 62% is presented. Printed in Brazil-