Synthesis of Picramide Using Nitration and Ammonolysis in Continuous Flow

Abstract This paper describes a safer, scalable and continuous process for synthesis of picramide. The process consists of two steps: step‐1. nitration of p ‐nitroanisole (PNAN) to 2,4,6‐trinitrianisole (TNAN); step‐2. ammonolysis of TNAN to picramide. Both the steps were optimized in flow, with yield of 90% and 98% in step‐1 and step‐2 respectively. Picramide with HPLC purity greater than 99% was obtained. When compared with batch, in step‐1, flow process provided significant advantage in selectivity and yield. The optimized flow process was scaled to 25 g/hr production rate in a laboratory flow reactor. The method can be considered fit for the safe production of picramide at commercial scale.