Continuous screening using mesoscale oscillatory baffled reactors

Abstract

A mesoscale Oscillatory Baffled Reactor (“mesoscale-OBR”) is a laboratory-scale reactor (5mm inner diameter) with a total volume of approximately 5.5mL containing equally spaced baffles. Due to its small volume, it is suitable as a platform technology for process screening or investigating reaction kinetics. Traditionally, these are conducted in batch; however, continous screening can be performed in the mesoscale-OBR, with flexible adjustment of the input and reduced reagent usage. In this project, continuous dynamic and “steady state” screening was demonstrated in the mesoscale-OBR. These techniques can be used to rapidly and logically obtain process data and kinetics of any liquid-liquid reactions. Exothermic reactions of several aldehydes (benzaldehyde, o-tolualdehyde, m-tolualdehyde and p-tolualdehyde) with n-butylamine to form imines were chosen as the case studies to demonstrate the ability of the mesoscale-OBR. Online FTIR was used to monitor reactions. The mesoscale-OBR exhibited a high degree of consistency in experimental results: the uncertainty in the rate constant for benzaldehyde and n-butylamine imination was three times lower than in a conventional batch beaker method. MATLAB was used to model reaction kinetics and validated using experimental data. Both experiments and modelling demonstrated that the rate constant for 1-butanamine, N-(phenylmethylene)-synthesis was 2.1 x 10-1mol-0.9L0.9s-1 with total reaction order of 1.9 (1.7 for benzaldehyde and 0.22 for n-butylamine). The process development time when using “dynamic screening” (i.e continuous variation of one of the input parameters) was reduced by 50% compared to batch screening using beakers. A higher area to volume ratio of the mesoscale-OBR (than the beaker) allowed exothermic reactions to be screened safely and quickly e.g. temperature for solvent free imination was at ~40oC in a jacketed mesoscale-OBR, whereas ~90oC (above the boiling point of n-butylamine) for a jacketed beaker. To passively improve the temperature distribution along the length of the reactor, the centrally baffled mesoscale-OBR was constructed inside a thermosyphon: the temperature difference along the reactor length at residence times of 60s and 90s was reduced to 2oC, rendering the reaction safer and more amenable to determination of exothermic reaction kinetic parameters.