Tertiary Amines from Alcohols without Oxidants, Reductants or Alkyl Halides

为了制造药物和相关化合物，有时需要使用有毒化学品作为合成和制造的起始原料。这方面的一个例子是一类被称为烷基卤化物的化合物，它经常被用来与胺（许多药物中发现的含氮化合物）反应。烷基卤化物通常是有毒的，因为它们不仅与胺反应，而且与我们自己的DNA反应。DNA的烷基化意味着烷基卤化物通常是诱变剂和致癌物。毫不奇怪，越来越多的立法确保这些烷基卤化物不存在于最终的药物分子中，并严格控制生产过程。本项目拟进行的研究包括用醇类代替烷基卤化物作为这些反应的替代品。通常情况下，问题是，与烷基卤化物相比，醇是非常不活泼的，将不成功地实现预期的反应。然而，使用催化剂，我们设计了一种方法，包括暂时从醇中除去氢，以形成更具反应性的醛作为中间体。在醛与胺反应后，催化剂返回氢。总的来说，与烷基卤化物形成的产品相同，但使用了更安全、更便宜的醇。反应的唯一副产品是水，这使得这些过程清洁且对环境无害。为了作为一种有用的工业过程具有吸引力，我们将证明在更大的规模上运行这些反应是可能的。为了做到这一点，提出了化学与化学工程之间的合作。小规模的反应将适应更大规模，使用专门建造的反应器，这些反应器将模拟大规模制造药物分子所必需的反应。

In order to make pharmaceutical drugs and related compounds, it is sometimes necessary to use toxic chemicals as starting materials in their synthesis and manufacture. One example of this is a class of compounds known as alkyl halides, which are often used to react with amines (nitrogen-containing compounds which are found in many pharmaceutical drugs). Alkyl halides are often toxic because they not only react with amines, but also with our own DNA. This alkylation of DNA means that alkyl halides are often mutagens and carcinogens. Not surprisingly, there is increasing legislation to ensure that these alkyl halides are not present in the final drug molecule, and that the manufacturing processes are carefully contained. The proposed research in this project involves replacing the alkyl halides with alcohols as alternatives for these reactions. Normally, the problem is that alcohols are very unreactive in comparison with alkyl halides and would be unsuccessful in achieving the desired reaction. However, using catalysts, we have designed a method that involves temporarily removing hydrogen from the alcohols to form much more reactive aldehydes as intermediates. The catalyst returns the hydrogen after the aldehyde has reacted with the amine. Overall, the same products are formed as with alkyl halides, but safer, cheaper alcohols are used in their place. The only byproduct from the reaction is water, making these processes clean and environmentally benign.In order to be appealing as a useful industrial process, we will demonstrate that it is possible to run these reactions on a larger scale. In order to do this, a collaboration between Chemistry and Chemical Engineering is proposed. The small scale reactions will be adapted to a larger scale using purpose built reactors that will model reactions that would be necessary for the manufacture of drug molecules on a large scale.