Toward an inherently safer alternative for operating N-oxidation of alkylpyridines: Effect of N-oxide on lutidine - water phase separation

The N-oxidation of alkylpyridines is an industrially important reaction since it produces alkylpyridine N-oxides that are pharmaceutical intermediates. The aqueous hydrogen peroxide used to oxidize the alkylpyridine has a tendency to decompose during the reaction thereby introducing serious hazards for the process. The decomposition is accelerated during the N-oxidation of higher order alkylpyridines (lutidines, collidines) due to mass transfer limitations caused by the separation of the liquid into organic and aqueous phase. Also, the presence of phosphotungstic acid (catalyst) in the aqueous phase further intensifies the peroxide decomposition reducing the safety and efficiency of the process. The current work investigates the influence of the product N-oxide on the mixing between alkylpyridine and water, which is primarily responsible for the liquid phase heterogeneity during the N-oxidation. Ternary mixtures of 2,6-lutidine, 2,6-lutidine N-oxide and water were analyzed at 110 °C to determine phase separation compositions. It was found that extent of heterogeneity between 2,6-lutidine and water is reduced dramatically by the presence of 2,6-lutidine-N-oxide as indicated by the phase diagram. The results could be used to implement the inherent safety concept - “hybridization” to the N-oxidation system wherein the concentration of product N-oxide can be controlled to maintain a less hazardous environment.