权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

在过去几年中，科学界的重点发生了重大转变，转向更环保和更可持续的做法，这主要是由于对当前做法的影响、政府立法和废物处理（特别是溶剂）成本增加的认识有所提高。在化学领域，对更高的效率、更低的溶剂使用、更低的能耗和改进的工艺的需求日益增加。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”来积极推动这一转变，包括Dial-a-Molecule（100%高效合成）和CO2 Chem（利用CO2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其他领域已被证明是有效的，可以提高效率和降低成本，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一直进展缓慢。在传统的研究环境中，这一点可以通过缺乏计算机辅助来清楚地看到，即使是最普通的任务，如滴定，结晶，萃取或蒸馏。当考虑更复杂的活动时，例如识别，优化和分析新反应，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开创化学合成的新方法，我们有能力提供一个新的愿景，这将导致解决目前的约束和限制，我们如何在实验室工作的今天。我们对未来实验室的愿景是摆脱低效的传统，通过将现代计算能力与最有用的软件开发相结合，以智能地组合联合收割机合成程序，推动化学合成的可能性。在过去的几年中，在开发新的流动合成使能工具方面投入了大量的精力，最显著的是在提高反应能力的领域。与此同时，新的在线检测方法正在开发中，台式NMR光谱仪和在线微型MS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的辅助工具，但人们很少关注必要的连续下游处理工具，如后处理循环和色谱法。在需要分离具有相似化学性质的化合物的情况下，色谱法通常是首选方法。研究人员可以很容易地使用半制备型和制备型HPLC来合理快速地分离化合物。手动柱色谱法和半自动快速色谱法的使用是常见的。然而，对于多组分、复杂的混合物，不存在用于化合物的在线连续分离的解决方案，特别是在研发规模上。能够在线色谱分离化合物（例如，在连续流多步反应序列中）具有巨大的便利性，并且就可以获得的许多益处和经济性而言，它另外具有吸引力。然而，在目前的时间，有没有设备，可以方便地实现这一点，在研究环境中，因此，我们的建议的基础是满足这样的需求：设计，建造和开发的第一个平行柱SFC分离装置在线使用，在R&D规模的合成，在流动化学应用。利用CO2超临界流体色谱能够以可持续和环境友好的方式进行快速分离，同时满足下游加工中未满足的需求。