Synthesis of Picramide Using Nitration and Ammonolysis in Continuous Flow

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.

Automated summary

This paper presents a safer, scalable, and continuous process for synthesizing picramide. The process consists of two steps: nitration of p-nitroanisole (PNAN) to 2,4,6-trinitrianisole (TNAN) in the first step, and ammonolysis of TNAN to picramide in the second step. Flow optimization resulted in yields of 90% and 98% for step-1 and step-2 respectively, with HPLC purity greater than 99% for the obtained picramide. The flow process offers significant advantages in selectivity and yield compared to the batch process in step-1. The optimized flow process was successfully scaled up to a production rate of 25 g/hr in a laboratory flow reactor, demonstrating its suitability for commercial-scale production of picramide.