Synthesis of Picramide Using Nitration and Ammonolysis in Continuous Flow
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Updated: Aug 18, 2025

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
Ankit Kumar Mittal1, Gaurav Prakash1, Pramod Pathak1
1Department of Chemistry, Indian Institute of Technology Bombay Powai, Mumbai, 400076, India.
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.
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