Reactor intensification for continuous multiphase fine chemical synthesis

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Many fine chemicals and pharmaceuticals are produced by solvent-intensive (semi)-batch processes increasing costs and environmental impact. In comparison, continuous-flow miniature reactors offer a large surface-to-volume ratio and intimate contact between reactants, which leads to very high heat and mass transfer rates, permitting improved reaction control and selectivity at more severe operating conditions. This and their small volume enable safer handling of hazardous reactions and unstable intermediates. The overall goal of this research program is thus to develop continuous-flow micro/milli-scale reactor technology that can robustly outperform current (semi)-batch reactors for a variety of single and multiphase fine chemical reactions over production rates spanning the clinical trials (1 to 600 ml/min) up to commercialization (e.g., single product mini-plant). Reactor miniaturization, along with more efficient reaction pathways and automated procedures (i.e., industry 4.0), will process intensify the fine chemical and pharmaceutical industries and is a fundamental technical shift for an industry reliant on primarily (semi)-batch processing within Good Manufacturing Practices. Over the last few years, we developed a "toolbox" concept where well-suited continuous micro/milli-reactor geometries and modes of operation are categorized based on the reaction network, intrinsic kinetics and phases present. Our research has systematically created high performing micro-reactors for liquid and immiscible fluid systems, whereas catalogued reactors involving solids still require advances for intensification. Therefore, the specific objectives of this research proposal are to A) develop reactors optimal for solids-forming reactions and B) model the proposed liquid-(solid) phase reactors via computational fluid dynamics. Miniaturized continuous reactors that handle particulates with less risk of clogging or losing performance will lead to much greater penetration of process intensification into the industry since precipitation reactions are an important class of fine chemical syntheses, while modelling will help identify effective mixing conditions and guide the experimental design in part A). An important challenge to the continuous manufacturing of fine chemicals and pharmaceuticals is to financially justify the major cost of transitioning from a known (available skilled personnel) and often depreciated batch technology with established business and regulatory processes in multiple countries. Graduate students will thus be comprehensively trained in a professional, diverse and inclusive team within a multi-disciplinary engineering/science/political science environment since policy-making affects technology development by engineers and chemists and vice versa. This will help accelerate changes for effective manufacturing in the fine chemical and pharmaceutical industries, which are important contributor to Canada's economy and human well-being.