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

虽然重点放在发展连续流动反应上，但对连续分离的关注要少得多。这些通常是化学品制造中最昂贵的部分，因为生产力和周期时间被忽略了。该项目的目的是开发自动化的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反应，如转氨酶，或大多数化学反应。该系统将在预测和自我优化模式下进行测试。预测方法包括测量和模拟组分pKa和分配系数，给出萃取操作的pH值。如果精确控制，具有相似pKa的胺可以选择性地提取。一个例子是从2-甲基苄胺中选择性提取n -苄基-2-甲基苄胺。另外，自优化方法可以通过连续测量收率/选择性来确定提取条件，如溶剂、pH、浓度、相比、温度等输入变量的变化。这种方法不需要测量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，在一个连续的过程中去除下一种物质（不需要的副产品浪费，或回收的起始物质）的能力突出了自动化控制系统的重要性。第二次分离的pH值将取决于第一次萃取，因此使用预定的设定值不再可行。串联使用不同的膜（疏水、亲水、mwt -cut- cut、吸附）将允许对不同的反应组分进行顺序分离。其中一些正在另一个刚刚启动的阿斯利康资助的案例奖中开发，这将有机会将这些项目有效地联系起来。该项目的预期结果是一种高效和高产的胺和酸连续分离工艺，应该广泛适用于制药开发管道；更深入地了解决定连续分离系统的基本过程；提高生产力和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保持一致，以便学生可以相互告知。阿斯利康的参与对于提供正确的方向、有用的范例和将技术转让给工业至关重要。

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.