Optimisation of Palladium-Catalysed C-H Activation Reactions

钯催化碳氢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。与传统使用的交叉耦合相比，这是通过缩短合成路线来实现的。然而，文献中存在的这种化学反应的大多数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，这意味着催化剂分离是具有挑战性的，通常需要使用清除剂或净化二氧化硅。当产品必须达到一定的标准时，这一点尤为重要，例如，钯在API中只能存在于每克API中10微克的水平。钯是一种稀有而昂贵的金属，通过从同质来源转向异质来源，最大限度地提高其再利用率，并最大限度地减少其在化学产品中的残留，将是有利的。为了最大限度地发挥钯催化C-H活化的功效，希望在不损害产品质量的情况下最小化温度和/或反应持续时间。提出的解决办法和方法提出了一套有利的条件来解决手头的问题。涉及多相催化，微波加热和流动化学。多相催化将用于实现更好的催化剂重复使用和分离。异相催化剂的使用为微波加热提供了选择性加热的可能性。这使得较高的反应温度更容易达到，随后减少反应持续时间。具有合适介电性能的固体载体应有利于吸收微波能量，在催化剂的位置迅速加热。微波必须能够穿透反应混合物有效地加热，因此，使用微波加热散装混合物是具有挑战性的。为了增加规模，还提出了一个流动系统，以确保微波加热保持规模效率，在给定时刻，通过最小化反应体积。此外，这提供了固定催化剂的机会，进一步提高了可重用性和易于分离。预计所提出的方法将提供一种方便的方法来达到或超过所需的温度，从而提高反应速率，使这种化学更容易获得和适用，特别是在更大的范围内。

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.