Multifunctional Electrochemical Flow Platform for High-Throughput Synthesis & Optimisation of Catalysts

我们将开发新技术，大大加快发现、开发和实施可持续发展的有机金属催化剂的进程，用于与工业相关的反应。制药、农业化学和精细化工过程中的许多反应都需要金属催化剂，这些催化剂依赖于铂族金属，如钯、铂和铑。(http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52014DC0297)，价格昂贵，被列入欧盟委员会2014年列出的20种关键原材料PGM，这些原材料存在供应减少的严重风险。此外，PGM是有毒的，因此必须从最终产品中去除，以达到通常难以达到/成本很高的水平(活性药物成分的含量为5ppm)。因此，目前在化学工业中越来越多地使用PGMS在中长期内是站不住脚的。贱金属，如铜和铁，更有吸引力用作催化剂，因为它们的储量要丰富得多，而且通常毒性较低(取决于形态)。尽管如此，贱金属在催化中的应用在工业上很少见；对贱金属催化剂的活性物种和机理轮廓缺乏了解，这意味着反应是不可预测的，而且往往是不可重现的。贱金属催化剂的研究比PGMS更具挑战性。此外，通常需要很高的催化剂负载量和苛刻的反应条件(与钯催化的反应相比)。通常使用线性过程发现和开发催化剂，在特定的反应中设计和合成、测试和优化催化剂，在优化的条件下检查底物范围，并重新设计以尝试和生产更具活性和选择性的(第二代)催化剂。除了缓慢和劳动密集型外，这一过程还有可能忽视潜在的有价值的催化剂。例如，由于时间限制，第二代催化剂只能在最适合第一代催化剂的条件下进行测试，而替代和改进的条件可能更适合。这项建议旨在将化学和工程领域的一系列互补专业知识结合在一起，以开发能够快速合成、筛选和自我优化贱金属催化剂的新技术。催化剂合成和催化反应阶段都将在流动池中进行，这使得能够在线分析每个阶段的输出，并允许在反应进行时修改条件。我们将使用算法，使反应变得自我优化，即根据分析数据自动改变条件，以便在相对较短的时间内为多个催化剂筛选几套条件。我们的目标是使这项技术被学术和工业实验室采用，以开发更广泛的催化剂。我们将开放所有与反应堆设计、变量、算法等相关的信息，以便其他研究人员可以复制和应用该技术。与贱金属催化反应有关的数据将被添加到一个可搜索的数据库中；这将为研究这些类型的反应的其他人提供宝贵的资源，使催化剂开发能够采用更基于知识和前沿的方法。

We will develop new technology that greatly accelerates the process of discovering, developing and implementing sustainable organometallic catalysts for industrially-relevant reactions.Many reactions in pharmaceutical, agrochemical and fine chemicals processes require metal catalysts which rely on platinum group metals (PGMs) such as palladium, platinum and rhodium. PGMs are expensive and are on the European Commission's 2014 list of 20 critical raw materials (http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52014DC0297), which possess serious risk of dwindling supply. Furthermore, PGMs are toxic, hence must be removed from final products to levels that are often difficult/costly to achieve (<5ppm for active pharmaceutical ingredients). The currently increasing use of PGMs in the chemicals industry is therefore untenable in the medium to long-term. Base-metals such as copper and iron are much more attractive to use as catalysts due to being significantly more abundant and typically having lower toxicity (depending upon speciation). Despite this, the use of base-metals in catalysis is rare in industry; a lack of understanding of the active species and mechanistic profiles of base-metal catalysts, which are more challenging to study than PGMs, means that reactions are unpredictable and often irreproducible. In addition, high catalyst loadings and harsh reaction conditions (when compared to, for example, palladium-catalysed reactions) are usually required.Catalysts are generally discovered and developed using a linear process, whereby a catalyst is designed and synthesised, tested and optimised in a specific reaction, examined for substrate scope under optimised conditions, and redesigned to try and produce more active and selective (2nd generation) catalysts. In addition to being slow and labour intensive, this process risks overlooking potentially valuable catalysts. For example, due to time constraints, a 2nd generation catalyst may only be tested under conditions that are optimum for the 1st generation catalyst, when alternative and improved conditions could be more suitable.This proposal seeks to bring together a range of complementary expertise across chemistry and engineering to develop new technology that is capable of rapidly synthesising, screening and self-optimising base-metal catalysts. Both the catalyst synthesis and catalytic reaction stages will be performed in flow cells, which enables online analysis of the output at each stage, and allows modification of the conditions as the reactions are running. Algorithms will be used so that the reactions become self-optimising i.e. conditions are automatically varied in response to the analytical data, enabling several sets of conditions to be screened for a number of catalysts within a relatively short period of time.Our aim is for the technology to be adopted by both academic and industrial laboratories for the development of catalysts more broadly. We will make all information relating to reactor designs, variables, algorithms etc. open access, so that other researchers can replicate and apply the technology. Data relating to base-metal catalysed reactions will be added to a searchable database; this will provide a valuable resource to others studying these types of reactions, enabling a more knowledge-based and frontier-leading approach to catalyst development.