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

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

Jingyao Wang^†,‡, Yanyan Huang^¡ì,#, Benjamin A. Wilhite^†,‡,, Maria Papadaki^‡,D, M. Sam Mannan^†,‡

† Artie McFerrin Department of Chemical Engineering, Texas A&M University, 3122 TAMU, College Station, Texas 77843-3122, USA

‡ Mary Kay O¡¯Connor Process Safety Center, Texas A&M University, 3122 TAMU, College Station, Texas 77843-3122, USA

¡ì Department of Chemistry, Texas A&M University, College Station, Texas, USA

# CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

D Department of Environmental and Natural Resources Management, School of Engineering, University of Patras, Seferi 2, Agrinio 30100, Greece

ABSTRACT

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 demonstrates the use of response surface methodology in search for inherently safer and more efficient intensified reaction conditions for 3-methylpyridine N-oxidation reaction performed in a semi-batch pressure-resistant isothermal calorimeter. The experimental conditions are broadly selected to screen various operating variables combinations using Box-Behnken design of experiments. Regression models are developed correlating the catalyst amount, oxidizer dosing rate and reaction temperature with reactor pressure and N-oxide yield showing good agreement with experiments in this study and past literature. It is plausible that, even when conducted in a semi-batch mode, the reaction is inherently safer and more efficient under intensified reaction conditions.

Keywords: process intensification, reaction engineering, response surface methodology, reactor safety, semi-batch reactor, inherently safer design