Tertiary Amines from Alcohols without Oxidants, Reductants or Alkyl Halides

不含氧化剂、还原剂或烷基卤的醇中的叔胺

• 批准号: EP/F015690/1
• 负责人: Jonathan Williams
• 金额: $ 36.91万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF015690%2F1
• 关键词: Tertiary; Amines; Alcohols; without; Oxidants

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.

为了制造药物和相关化合物，有时需要使用有毒化学物质作为合成和制造的原料。这方面的一个例子是一类被称为烷基卤化物的化合物，它经常用于与胺(在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，还与我们自己的DNA反应。DNA的这种烷基化意味着烷基卤化物通常是诱变剂和致癌物。不足为奇的是，有越来越多的立法来确保这些烷基卤化物不存在于最终的药物分子中，并确保制造过程得到谨慎控制。该项目中拟议的研究涉及用醇取代卤代烃作为这些反应的替代品。通常情况下，问题是与卤代烃相比，醇是非常不活泼的，不能成功地实现所需的反应。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，以形成更多的活性醛作为中间体。在醛与胺发生反应后，催化剂返回氢气。总体而言，生成的产品与烷基卤化物相同，但它们的位置使用了更安全、更便宜的酒精。反应的唯一副产品是水，使这些过程清洁和环境友好。为了吸引人作为一个有用的工业过程，我们将证明有可能在更大范围内运行这些反应。为了做到这一点，化学和化学工程之间的合作被提出。小规模的反应将被改造成更大的规模，使用专门建造的反应器来模拟大规模制造药物分子所必需的反应。

项目成果

Borrowing Hydrogen. C—N Bond Formation from Alcohols

• DOI: 10.1002/chin.200935228
• 发表时间: 2009-09
• 期刊: ChemInform
• 作者: Gareth W. Lamb;Jonathan M. J. Williams