Optimisation of Palladium-Catalysed C-H Activation Reactions

钯催化 C-H 活化反应的优化

• 批准号: 2279281
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2279281
• 关键词: Optimisation; Palladium; Catalysed; Activation; Reactions

Palladium-catalysed C-H activation chemistry provides a means to reduce waste and cost associated with syntheses. This occurs through the shortening of synthetic routes when compared to traditionally used cross-couplings. However, most examples of this chemistry that exist in literature feature high reaction temperatures and long reaction durations. Heterogeneous catalysts are rarely used, meaning catalyst separation is challenging, usually requiring use of scavengers or purification on silica. This is particularly important where the product must be held to certain standards, for instance palladium can only exist in API's at a level of 10 micrograms per gram of API. Palladium is a rare and expensive metal, it would be advantageous to maximise its re-use, and minimise its retention in chemical products through moving away from homogeneous sources and towards heterogeneous sources.To maximise the efficacy of palladium-catalysed C-H activation, it's desirable that the temperature and/or reaction duration can be minimised, without detriment to the quality of the product. Proposed solution and methodologyA complimentary set of conditions has been proposed to tackle the issues at hand. Involved would be heterogenous catalysis, microwave heating and flow chemistry.Heterogeneous catalysis will be used to achieve better catalyst reusability and separation. The use of a heterogeneous catalyst opens up the possibility of selective heating when coupled with microwave heating. This allows the high reaction temperatures to be accessed more easily, subsequently reducing reaction duration. A solid support with suitable dielectric properties should favourably absorb microwave energy, rapidly heating at the location of the catalyst. Microwaves must be able to penetrate the reaction mixture to heat effectively, therefore, heating a bulk mixture is challenging using microwaves. In order to increase the scale, a flow system is also proposed to ensure microwave heating maintains efficiency at scale, by minimising the reaction volume at a given moment. Additionally, this provides the opportunity to immobilise the catalyst, further enhancing reusability and ease of separation.It is anticipated that the proposed methodology will provide a convenient way of reaching or exceeding the desired temperatures, thus enhancing the reaction rate and making this chemistry more accessible and applicable, especially on a larger scale.

钯催化的C-H活化化学提供了一种减少与合成相关的浪费和成本的方法。与传统使用的交叉偶联相比，这是通过缩短合成路线实现的。然而，文献中存在的大多数这种化学的例子都具有高反应温度和长反应持续时间的特点。多相催化剂很少使用，这意味着催化剂的分离具有挑战性，通常需要使用清除剂或对二氧化硅进行提纯。当产品必须符合某些标准时，这一点尤其重要，例如，原料药中的钯只能存在于每克原料药10微克的水平。钯是一种稀有而昂贵的金属，通过从均相源转移到多相源，最大限度地提高其重复利用率，并将其在化学产品中的保留量降至最低。为了最大限度地提高钯催化的C-H活化的效率，最好能最大限度地降低温度和/或反应时间，而不会损害产品的质量。拟议的解决办法和方法提出了一套相辅相成的条件来解决手头的问题。包括多相催化、微波加热和流动化学等，多相催化将实现更好的催化剂重复使用和分离。多相催化剂的使用打开了选择加热的可能性，当与微波加热相结合时。这使得更容易获得较高的反应温度，从而缩短了反应持续时间。具有合适介电性能的固体载体应有利于吸收微波能量，并在催化剂位置快速加热。微波必须能够有效地穿透反应混合物来加热，因此，使用微波加热散装混合物是具有挑战性的。为了扩大规模，还提出了一种流动系统，通过最小化给定时刻的反应体积，确保微波加热保持规模的效率。此外，这为催化剂的固定化提供了机会，进一步提高了可重用性和易分性。预计拟议的方法将提供一种达到或超过所需温度的便捷方法，从而提高反应速度，使这种化学更容易获得和应用，特别是在更大范围内。