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.

在过去的几年中，科学界的重点已经发生了重大的转变，在很大程度上是由于对当前实践的影响，政府立法和增加废物处置成本的认识，这在很大程度上是在环保和可持续性的。溶剂）。在化学世界中，人们对更高效率，较低的溶剂使用，较低的能耗和改进的过程的需求增加。浪费且耗时的做法不再是可以接受的，迫使化学家对自己的行为负责。 EPSRC承认这一转变的重要性，并通过创建一系列“巨大挑战”（包括拨号分子（100％效率合成）和CO2CHEM（利用CO2进行化学合成））来积极推动这种转变。尽管如此，尽管如此，尽管计算机辅助的过程和电子自动化已被证明在其他领域有效，但提高效率并最大程度地降低了成本，但作为一门科学的化学作用对旨在帮助化学家进行常规任务的新技术的吸收缓慢。在传统的研究环境中，即使在最普通的任务（例如滴定，结晶，提取或蒸馏）中，缺乏计算机援助，这可以清楚地看到这一点。当查看更复杂的活动，例如对新反应的识别，优化和分析，情况甚至更糟。如果我们要向前推进化学，这必须改变。我们的研究小组一直开创了化学合成中新型方法的开创性，我们在实现新的愿景方面处于良好状态，这将导致解决当今我们在实验室工作的当前限制和局限性。我们对未来实验室的愿景是从效率低下的传统中脱颖而出，并通过将现代计算能力与最有用的软件开发相结合，以智能结合综合程序，从而突破了化学合成中可能的界限。在过去的几年中，在开发新的流合成促进工具方面已经花费了大量的努力，最值得注意的是在增强反应能力的领域。同时，正在开发新的在线检测方法，其中包括桌面NMR光谱仪和在线微型MS检测器，可为流量产生的化合物迅速提供广泛的化学结构数据。尽管这些新的启用工具进入市场的增加，但几乎没有关注基本的连续下游加工工具，例如工作周期和色谱法。在需要分离具有相似化学特性的化合物的情况下，色谱法通常是选择方法。研究人员很容易地使用半预编制和制备的HPLC快速分离化合物。手动色谱柱色谱法和半自动化闪光色谱法很常见。但是，对于多组分，复杂的混合物没有用于在线连续分离化合物的解决方案，尤其是在研发量表上。能够在线色谱化合物（例如，在连续流动反应序列中）具有巨大的便利性，并且就可以获得的许多好处和经济体而言，它也具有吸引力。然而，目前，在研究环境中没有任何设备可以方便地实现这一目标。因此，我们的提案的基础是满足这种需求：在流动化学应用中设计，构建和开发第一个平行列SFC分离设备，以在综合的R＆D量表上使用。利用CO2超临界流体色谱法可以以可持续和环保的方式快速分离，同时满足下游处理的未满足需求。