Reactor intensification for continuous multiphase fine chemical synthesis

用于连续多相精细化学品合成的反应器强化

• 批准号: RGPIN-2020-04078
• 负责人: Macchi, Arturo
• 金额: $ 3.35万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746798
• 关键词: Reactor; intensification; continuous; multiphase; fine

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.

许多精细的化学物质和药物都是由溶剂密集型（半批量）过程产生的，从而增加了成本和环境影响。相比之下，连续流微型反应堆提供了较大的地表与体积比和反应物之间的亲密接触，这会导致非常高的热量和质量转移率，从而可以在更严重的工作条件下提高反应控制和选择性。这及其少量能够更安全地处理危险反应和不稳定的中间体。因此，该研究计划的总体目标是开发连续流动/毫米尺度的反应器技术，该技术可以强劲地比临床试验（1至600 mL/min）的生产率（例如，单个产品）进行商业化（例如，单个产品的单个产品），对各种单一和多层细胞化学反应的表现都超过了电流（SEMI） - 批量反应器。反应堆的微型化以及更有效的反应途径和自动化程序（即行业4.0）将加强良好的化学和制药行业，并且是主要依赖（半近牙）处理良好制造实践中的行业的根本技术转变。在过去的几年中，我们开发了一个“工具箱”概念，其中合适的连续微/毫米反应器几何形状和操作模式根据反应网络，固有动力学和存在的相分类。我们的研究系统地为液体和不混溶的流体系统创建了高性能的微反应器，而涉及固体的分类反应器仍需要进步才能进行强化。因此，本研究建议的特定目标是a）开发用于固体形成反应的反应器，b）通过计算流体动力学对提出的液体（固体）相应器进行建模。微型连续反应器处理具有较小风险堵塞或失去性能的颗粒物的小型反应器将导致工艺强化对行业的渗透率更大，因为降水反应是一类优质化学合成的重要类别，而建模将有助于识别有效的混合条件并指导A部分A）。不断制造精美的化学品和药品的一个重要挑战是在经济上证明从已知的（可用的熟练人员）过渡的主要成本是合理的，并且经常在多个国家使用已建立的业务和法规流程折磨的批处理技术。因此，研究生将在多学科工程/科学/政治科学环境中的专业，多样化和包容性团队中进行全面培训，因为决策会影响工程师和化学家的技术发展，反之亦然。这将有助于加速在精细的化学和制药行业中有效制造的变化，这是加拿大经济和人类福祉的重要贡献。