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Development of Automated Parallel CO2 Supercritical Fluid Chromatography for Use in Continuous Flow Chemical Synthesis

开发用于连续流动化学合成的自动平行 CO2 超临界流体色谱

基本信息

批准号：
EP/M004120/1
负责人：
Steven Ley
金额：
$ 71.96万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FM004120%2F1
关键词：
Development Automated Parallel CO2 Supercritical

项目摘要

There has been a significant shift in focus within the scientific community over the previous few years towards practices that are more environmentally accessible and sustainable, driven largely by increased awareness of the impacts of current practice, governmental legislation and increasing costs of waste disposal (most especially solvents). In the chemistry world there are increasing demands for greater efficiencies, lower solvent use, lower energy consumption and improved processes. Wasteful and time-consuming practices are no longer acceptable, forcing chemists to be more responsible for their actions. The EPSRC has acknowledged the importance of this shift and is actively promoting it through the creation of a series of 'Grand Challenges' including Dial-a-Molecule (100% efficient synthesis) and CO2Chem (utilising CO2 for chemical synthesis). Unusually, although computer-aided processes and electronic automation have been shown to be effective in other sectors at increasing efficiency and minimising costs, chemistry as a science has been slow on the uptake of new technology designed to assist chemists in routine tasks. In the traditional research environment, this can be seen most clearly by the lack of computer assistance in even the most ordinary of tasks such as titrations, crystallisations, extractions or distillations. When looking at more complex activities such as the identification, optimisation and analysis of new reactions, the situation is even worse. This must change if we are to move chemistry forward. Our research group has consistently pioneered novel methods in chemical synthesis and we are well positioned to deliver a new vision that will lead the way in addressing the present constraints and limitations of how we work in the laboratory today. Our vision of the Lab of the Future is one that breaks away from inefficient traditions and pushes the boundaries of what is possible in chemical synthesis by combining modern-day computing power with the most useful of software developments in order to intelligently combine synthesis procedures.During the last few years there has been a significant amount of effort expended in the development of new flow synthesis enabling tools, most notably in the area of enhancing reaction capability. At the same time new in-line detection methods are being developed, with desktop NMR spectrometers and in-line miniature MS detectors providing extensive chemical structure data rapidly for compounds produced in flow. Despite the increase in these new enabling tools coming onto the market, there has been little focus on essential continuous downstream processing tools such as work-up cycles and chromatography.In situations where compounds having similar chemical properties need to be separated, chromatography is usually the method of choice. Researchers are easily able to use semi-preparative and preparative HPLC to separate compounds reasonably quickly. The use of manual column chromatography and semi-automated flash chromatography is commonplace. However for multi-component, complex mixtures there exist no solutions for in-line continuous separation of compounds, especially on an R&D scale. There are huge conveniences to being able to chromatograph compounds in-line (e.g. in a continuous flow multistep reaction sequence) and it is additionally attractive in terms of many benefits and economies that can be obtained. At the current time, however, there exist no devices that can conveniently achieve this in the research environment; the basis of our proposal therefore is to meet such a need: to design, build and develop the first parallel column SFC separation device for use in-line, at the R&D scale of synthesis, in flow chemistry applications. Utilising CO2 supercritical fluid chromatography enables rapid separations in a sustainable and environmentally friendly manner while fulfilling an unmet need in downstream processing.

过去几年来，科学界的重点已明显转向更容易在环境上获得和可持续的做法，这主要是由于对当前做法的影响的认识提高、政府立法和废物处理（尤其是溶剂）成本的增加。在化学领域，人们对更高的效率、更低的溶剂用量、更低的能耗和改进的工艺要求越来越高。浪费和耗时的做法不再被接受，迫使化学家对他们的行为更加负责。EPSRC已经认识到这一转变的重要性，并通过创建一系列“大挑战”积极推动这一转变，包括Dial-a-Molecule（100%高效合成）和CO2Chem（利用二氧化碳进行化学合成）。不同寻常的是，尽管计算机辅助过程和电子自动化在提高效率和降低成本方面已被证明在其他部门是有效的，但化学作为一门科学，在吸收旨在帮助化学家完成日常任务的新技术方面进展缓慢。在传统的研究环境中，即使是最普通的任务，如滴定、结晶、提取或蒸馏，也缺乏计算机辅助，这一点可以最明显地看出。当着眼于更复杂的活动，如新反应的识别、优化和分析时，情况甚至更糟。如果我们要推动化学向前发展，这种情况必须改变。我们的研究小组一直在化学合成方面开创新方法，我们有能力提供一个新的愿景，这将引领我们解决目前在实验室工作的制约和限制。我们对未来实验室的愿景是，通过将现代计算能力与最有用的软件开发相结合，以智能地组合合成过程，打破效率低下的传统，推动化学合成的可能性。在过去的几年里，人们在开发新的流动合成工具方面投入了大量的精力，尤其是在提高反应能力方面。与此同时，新的在线检测方法正在开发，台式核磁共振光谱仪和在线微型质谱检测器可以快速提供流动中产生的化合物的广泛化学结构数据。尽管市场上出现了越来越多的新型工具，但人们很少关注基本的连续下游处理工具，如处理循环和色谱。在需要分离具有相似化学性质的化合物的情况下，色谱法通常是选择的方法。研究人员可以很容易地使用半制备型和制备型高效液相色谱来合理快速地分离化合物。使用手动柱层析和半自动闪蒸层析是司空见惯的。然而，对于多组分、复杂混合物，目前还没有实现化合物在线连续分离的解决方案，尤其是在研发规模上。能够在线（例如，在连续流多步反应序列中）对化合物进行色谱分析有很大的方便，并且就可以获得的许多好处和经济而言，它还具有吸引力。然而，在目前的研究环境中，还没有一种设备可以方便地实现这一点；因此，我们建议的基础是满足这样的需求：设计，建造和开发第一个平行柱SFC分离装置，用于在线，在合成的研发规模，在流动化学应用。利用CO2超临界流体色谱法可以实现可持续和环保的快速分离，同时满足下游处理的未满足需求。