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，有时必须将有毒化学物质用作其合成和生产的起始材料。其中一个例子是一类称为烷基卤化物的化合物，它们通常用于与胺反应（在许多药物中发现的含氮化合物）。烷基卤化物通常是有毒的，因为它们不仅与胺反应，而且还与我们自己的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。毫不奇怪，有越来越多的立法可以确保最终药物分子中不存在这些烷基卤化物，并且仔细地包含了制造过程。该项目的拟议研究涉及用醇作为这些反应的替代烷基卤化物。通常，问题在于，与烷基卤化物相比，酒精非常不反应，并且无法成功实现所需的反应。但是，使用催化剂，我们设计了一种方法，涉及暂时去除酒精中的氢，以形成更具反应性的醛作为中间体。醛与胺反应后，催化剂返回氢。总体而言，与烷基卤化物形成相同的产品，但使用更便宜，更便宜的酒精。反应中唯一的副产品是水，使这些过程清洁和环境良性。为了作为有用的工业过程吸引人，我们将证明有可能在更大范围内进行这些反应。为此，提出了化学与化学工程之间的合作。小规模的反应将使用专用的反应器来适应更大尺度的反应，该反应器将模拟大规模制造药物分子所必需的反应。