Towards the Identification of Intensified Reaction Conditions using Response Surface Methodology: A Case Study on 3-Methylpyridine N-oxide Synthesis

Identification of inherently safer and intensified reaction conditions is a vital step for transformation of traditional batch/semi-batch synthesis to continuous operation. Speeding up reactions is challenged by several safety and efficiency issues such as thermal runaway risk, side reactions, final product degradation and reactor overpressure. This work presents a case study of 3-methylpyridine N-oxidation to demonstrate the use of response surface methodology in the search for inherently safer and more efficient intensified reaction conditions using a minimal number of experiments. The reactions were performed in a semi-batch pressure-resistant isothermal calorimeter RC1e by constant addition of aqueous hydrogen peroxide solution to catalytically oxidize the 3-methylpyridine. The experimental conditions were broadly selected using previous research on this system and they were further refined by design of experiments to screen the various combinations of operating variables. The final products were anal...