Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale

用于大规模生产交叉偶联反应的可回收催化剂技术

• 批准号: EP/K504105/1
• 负责人: Guy Lloyd-Jones
• 金额: $ 22.8万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK504105%2F1
• 关键词: Recyclable; Catalyst; Technology; Cross; Coupling

Homogeneous Palladium (Pd) cross-couplings, based on Nobel-prize winning methodologies, have become essential forthe production of life-enhancing pharmaceuticals & chemicals (est. worth to sector: >£10 bn). However there areenvironmental & sustainability issues, often addressed by heterogeneous Pd catalysts but with reduced performance. Thisproject combines the advantages of each type of Pd catalysis by development of a broad-spectrum 'Catch & Release'cross-coupling technology. Novel functionalised silica materials will allow purification of reaction products by temporarycapture of the Pd catalyst in heterogeneous form, capable of release back in it's active form into solution by new reactioncomponents for further production. The technology is employed in semi-continuous format, with application possible acrossmultiple process industries. Initial applications towards the manufacture of pharmaceuticals & agrochemicals will bedemonstrated. This project fits rigorously within the TSB competition's headline goal of providing 'Sustainablemanufacturing for the process industry' and describes an innovative 'Novel Catalysis' approach. This is delivered through atechnology which enables change from existing batch to semi-continuous processing and the development of inherentlymore sustainable processes, which recover & reuse the active catalysts, both metal and ligand, whilst dramatically reducing subsequent product purification requirements. The overarching objective is the identification and optimisation of anappropriately functionalised aryl bromide on the silica solid support to effectively catch & then release the active Pd catalystand to take this as proven technology into manufacture.Our consortium links academic and SME expertise in ligand design/immobilisation and understanding of metal-catalysedcouplings together with global industrial product end-users. The widespread application of transition metal (Pd) crosscouplingreactions in a variety of chemistry-related industries means the chosen subject material is of high and topicalimportance as the UK strives for faster production processes to increase it's competitive edge in manufacturing. Theproject's combination of the benefits of homogeneous Pd catalysis (fast reaction rates, selectivity and flexible catalystchoice) with the use of a solid phase to temporarily support the active Pd catalyst (for subsequent reuse) & simultaneouslyallow easy product purification will enable high efficiency chemical synthesis with increased throughput by semi-continuousprocessing. First development and then fine-tuning of the silica-supported linker to suitably effect the cross-couplingreaction step is critical to industry adoption of the final commercial product as a broad-spectrum, preferred method forcross-coupling at process scale; the project's activities and objectives reflect this. The output from this innovative andimproved catalytic route for cross-couplings will be observed by better process economics, through recycling of high costsynthetic metals, including Pd, and organic ligands, and reduced toxic waste outputs. The endpoint commercial productwould generate international interest and lead to export sales. In summary, our project focuses primarily on catalysisprocess innovation, through improvement of the lifetime and recycling of the Pd catalyst for cross-couplings by theintroduction of a heterogeneous stage to the catalytic cycle, which also serves as a reaction purification step.

基于诺贝尔奖获奖方法的均相钯（Pd）交叉偶联，已成为提高生命的药品和化学品生产的关键（该行业的价值：100亿英镑）。然而，存在环境和可持续性问题，通常由多相钯催化剂解决，但性能降低。该项目通过开发广谱“捕获与释放”交叉耦合技术，结合了每种类型Pd催化的优势。新型功能化二氧化硅材料将允许通过暂时捕获多相形式的Pd催化剂来纯化反应产物，能够通过新的反应组分释放回其活性形式的溶液中以进一步生产。该技术采用半连续形式，可应用于多个工艺行业。将演示在制药和农用化学品制造方面的初步应用。该项目严格符合TSB竞赛的标题目标，即为过程工业提供“可持续制造”，并描述了一种创新的“新型催化”方法。这是通过一项技术来实现的，该技术可以从现有的批量处理转变为半连续处理，并开发更可持续的工艺，回收和再利用活性催化剂，包括金属和配体，同时大大降低后续产品的净化要求。总体目标是鉴定和优化二氧化硅固体载体上不适当功能化的芳基溴，以有效捕获并释放活性钯催化剂，将其作为成熟的技术投入生产。我们的联盟将学术界和中小企业在配体设计/固定化方面的专业知识以及对金属催化偶联的理解与全球工业产品最终用户联系起来。过渡金属（Pd）交叉偶联反应在各种化学相关行业的广泛应用意味着所选择的主题材料具有很高的主题重要性，因为英国正在努力加快生产过程，以增加其在制造业的竞争优势。该项目结合了均相钯催化剂的优点（快速反应速率，选择性和灵活的催化剂选择），使用固相暂时支持活性钯催化剂（用于后续再利用），同时允许易于产品纯化，将通过半连续处理实现高效率的化学合成，提高吞吐量。首先开发然后微调二氧化硅支撑的连接剂，以适当地影响交叉耦合反应步骤，这对于工业采用最终的商业产品作为工艺规模上交叉耦合的广谱首选方法至关重要；项目的活动和目标反映了这一点。通过回收高成本合成金属（包括Pd）和有机配体，以及减少有毒废物的排放，这种创新和改进的交叉偶联催化途径的产出将通过更好的工艺经济来观察。终端商业产品将产生国际兴趣并导致出口销售。综上所述，我们的项目主要侧重于催化工艺创新，通过在催化循环中引入多相阶段（也作为反应净化步骤）来改善Pd催化剂的寿命和循环利用，以进行交叉偶联。