Development of continuous multiphase microreactors for the production of fine chemicals

许多精细化学品和药品是通过溶剂密集型间歇或半间歇工艺生产的，这增加了成本和环境影响。相比之下，连续流微反应器提供大的表面积与体积比和反应物之间的紧密接触，这导致非常高的传热和传质速率，从而允许在更严格的操作条件下改善反应控制和选择性。这一点和它们的小体积使危险反应和不稳定中间体的处理更安全。因此，该研究计划的总体目标是开发足够灵活的连续流微反应器技术，使其在从药物临床试验阶段I（10-50 ml/min）到III（400-600 ml/min）的生产规模上，能够在各种单相和多相反应中优于间歇/半间歇反应器。重点主要放在合成是高度放热和/或受相间传质限制的分子上，因为这些操作条件更难以优化。 本实验将系统地研究以下几个方面的问题：1）在不同的反应器几何结构中，无固载催化剂和有固载催化剂的气液两相流动的流体力学和输运现象。这将导致基于期望的接触模式和耗散能量的效率来选择混合结构的标准，以及稳健的缩放规则。2)烯烃的闭环复分解和腈的氢化，这是有机合成中至关重要的催化反应，并利用渥太华大学领先的化学专业知识。这将协同使用并为第1部分提供信息;在化学家和工程师之间形成更强的联系，从而同时优化催化剂/反应和反应器设计。部署在多学科科学/工程环境中培训的研究生将有助于加速制药行业制造业的变革，这是加拿大经济和福祉的重要贡献者。

Many fine chemicals and pharmaceuticals are produced by solvent-intensive batch or semi-batch processes increasing costs and environmental impact. In comparison, continuous-flow microreactors 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 microreactor technology sufficiently flexible that it can outperform batch/semi-batch reactors for a variety of single and multiphase reactions over production scales ranging from pharmaceutical clinical trial phases I (10-50 ml/min) to III (400-600 ml/min). Focus is primarily on molecules where synthesis is highly exothermic and/or limited by interphase mass transfer since these operating conditions are more difficult to optimize. A systematic and thorough experimental program will investigate: 1) Hydrodynamics and transport phenomena of gas-liquid flow without and with solid-supported catalyst in select and distinct reactor geometries. This will lead to criteria for choosing mixing structures based on desired contacting pattern and efficiency in dissipating energy, and to robust scaling rules. 2) Ring-closing metathesis of olefins and hydrogenation of nitriles, which are catalytic reactions of central importance in organic synthesis and take advantage of leading chemical expertise at the University of Ottawa. This will synergistically use and provide information towards part 1); forming stronger ties between chemists and engineers such that catalyst/reaction and reactor design are optimized concurrently. Deploying graduate students trained within a multidisciplinary science/engineering environment will help accelerate changes to manufacturing in the pharmaceutical industry, an important contributor to Canada's economy and well-being.