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

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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.