A Practical Approach of Continuous Processing to High Energetic Nitration Reactions in Microreactors

Abstract

Continuous processing in microreactors represents a novel way for the safe and expedient conduct of high energetic reactions and potentially hazardous chemistry. Apart from handling benefits (such as minimised problems inthe scale-up process), reactions in microreactors proceed under precisely controlled conditions providing improved yields and product quality compared to the batch procedure. In this paper, the potential of this technology is exemplarily determined in the crucial nitration of the pharmaceutically relevant intermediate 1-methyl-3-propyl-1H-pyrazole-5-carboxylic acid (1). Further fundamental nitration examples demonstrate the unproblematic handling of hazardous H 2 SO 4 / HNO 3 mixtures for the nitration of 2-methylindole (4) and pyridine-N-oxide (6) or even the explosive acetyl nitrate Ac 2 O/HNO 3 (nitration of toluene, 8) in the continuous reaction mode.