Selective Extraction of Amines and Acids By Continuous Flow Liquid-Liquid Extraction

通过连续流液液萃取选择性萃取胺和酸

• 批准号: 2819954
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2819954
• 关键词: Selective; Extraction; Amines; Acids; Continuous

Whilst great emphasis is being put on developing continuous flow reactions, far less attention is paid to continuous separations. These are often the most costly part of a chemical manufacture because productivity and cycle times are ignored. The aims of this project are to develop automated pH-controlled system for the selective continuous extraction and purification of amines and acids. This can also reduce waste by avoiding the use of buffers. The system can be used in reactions such as biotransformations, e.g. transaminases, or most chemical reactions. The system will be tested in predictive and self-optimisation modes. The predictive method involves measurement and modelling of component pKa and partition coefficients giving a a pH at which to operate the extraction. If controlled precisely, amines with similar pKa's can be selectively extracted. An example is the selective extraction of N-benzyl-2-methylbenzylamine from 2-methylbenzylamine. Alternatively, self-optimisation methodology can be used to determine the extraction conditions by measuring the yield/selectivity continuously as the input variables such as solvent, pH, concentration, phase ratio, temperature are changed. In this method no pH measurement is required. The ability to separate out one product after the reaction at a selected pH and then alter the pH of the remaining stream before passing into a further L-L separator (Zaiput), to remove the next species (unwanted side product to waste, or starting material to recycle) all in one continuous process highlights the importance of an automated control system. The pH of the second separation will be dependent on the first extraction so using predetermined set points is no longer feasible. The use of different membranes (hydrophobic, hydrophilic, MWt-cut-off, adsorptive) in series will allow sequential separation of different reaction components. Some of these are being developed in another just started AZ funded CASE award, and this will give the opportunity to usefully link these projects. The outcomes expected of this project are an efficient and productive continuous separation process for amines and acids that ought to be widely applicable to the pharma development pipeline; a deeper understanding of the underlying processes that determine the continuous separation systems; automated optimisation methods that improve productivity and reduce waste. The student will gain experience in a wide variety of techniques including physical-organic, chemistry and process chemistry and engineering, PAT, coding, control, analytical, flow chemistry, equipment and experimental design. It is planned to align this project with the current ones so that the students can inform each other. The involvement of AZ is critical in providing the right direction, useful exemplars and transfer of the technology into industry.

虽然人们非常重视开发连续流动反应，但对连续分离的关注却少之又少。这些通常是化学制造中成本最高的部分，因为生产率和周期时间被忽视。该项目的目的是开发自动 pH 控制系统，用于选择性连续提取和纯化胺和酸。这还可以通过避免使用缓冲区来减少浪费。该系统可用于生物转化等反应，例如转氨酶，或大多数化学反应。该系统将以预测和自我优化模式进行测试。预测方法涉及组分 pKa 和分配系数的测量和建模，给出进行提取的 pH 值。如果精确控制，可以选择性地提取具有相似 pKa 的胺。一个例子是从 2-甲基苄胺中选择性萃取 N-苄基-2-甲基苄胺。或者，当输入变量（例如溶剂、pH、浓度、相比、温度）发生变化时，可以使用自优化方法通过连续测量收率/选择性来确定提取条件。在此方法中不需要测量 pH 值。在选定的 pH 值下反应后分离出一种产物，然后在进入另一个 L-L 分离器 (Zaiput) 之前改变剩余流的 pH 值，以去除下一种物质（不需要的副产物进行废物处理，或起始材料进行回收），所有这些都在一个连续过程中，这凸显了自动化控制系统的重要性。第二次分离的 pH 值将取决于第一次提取，因此使用预定的设定点不再可行。串联使用不同的膜（疏水性、亲水性、截留分子量、吸附性）将允许顺序分离不同的反应组分。其中一些项目正在另一个刚刚启动的 AZ 资助的 CASE 奖项中开发，这将为有效链接这些项目提供机会。该项目的预期成果是一种高效、高效的胺和酸连续分离工艺，应广泛适用于药物开发管道；更深入地了解决定连续分离系统的基本过程；提高生产力并减少浪费的自动化优化方法。学生将获得各种技术的经验，包括物理有机、化学和过程化学与工程、PAT、编码、控制、分析、流动化学、设备和实验设计。计划将这个项目与当前的项目结合起来，以便学生们可以互相告知。 AZ 的参与对于提供正确的方向、有用的范例以及将技术转移到行业至关重要。