(608f) Aiding Safer and More Efficient Transformation from Batch to Continuous Flow Processing Via Nonlinear Dynamic Analysis

Authors: 
Mannan, M. S., Texas A&M University
Cui, X., Texas A&M University
Wilhite, B. A., Texas A&M University

The last decade bears witness to remarkable attempts by both academic pioneers and industrial practitioners to shift the way to discover and manufacture pharmaceuticals and fine chemicals. Continuous flow processes are deemed promising as alternatives to conventional semi-batch/batch ones for merits such as enhanced safety, improved productivity, and reduced environmental footprint, just to name a few.

Pyridine and its derivatives are widely used as starting materials for pharmaceuticals and agrochemicals syntheses. Among them are alkylpyridine N-oxides, which are conventionally obtained from the liquid phase, homogeneous catalytic N-oxidation of alkylpyridines using hydrogen peroxide as the oxidation agent and phosphotungstic acid (H3PW12O40) as the catalyst. Large reaction heat release along with the simultaneous exothermic and oxygen-generating decomposition reaction of hydrogen peroxide pose serious hazards associated with reaction runaway, which to-date have been addressed by carrying out the reaction in a semi-batch mode to control reaction rates.

In this presentation, classical reaction engineering principles together with process safety notions were utilized to explore inherently safer and economically feasible continuous stirred tank reactor (CSTR) designs for the aforementioned N-oxidation of alkylpyridines. Existence of multiple steady states and oscillations as well as their stability, depending on the dimensionless cooling number, adiabatic temperature rise, and Damköhler number, were determined based upon criteria derived from bifurcation theory and a first-principles CSTR model delineating conservation laws and complex reaction kinetics, which resulted in demarcation of the design and operation parameter plane. The demarcated plane was further screened against performance metrics such as the minimum required conversion and the desired temperature window to identify potential design and operation conditions. Start-up strategies were investigated via phase plot analysis, while evaluation of available response time in case of cooling failure (as one of the worst-case scenarios during reactor operation) and scale-up feasibility were also provided. It is believed that this study well serves as an illustrative example and a starting point of employing classical theories as powerful tools for proposing CSTR (or even more sophisticated tubular/membrane reactors as needed) design and operation guidelines for evolving from batch to continuous handling of pharmaceutical and fine chemical chemistry.