Development of a generally applicable catalytic direct amidation reaction

通用催化直接酰胺化反应的开发

基本信息

批准号：
EP/T030488/1
负责人：
Tom Sheppard
金额：
$ 42.85万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FT030488%2F1
关键词：
Development generally applicable catalytic direct

项目摘要

The formation of an amide functional group is one of the most common processes used in the synthesis of organic molecules both in academic labs and in the chemical industry. Whilst many effective methods exist for this reaction, all of the widely used approaches require the use of inefficient reagents which generate large quantities of waste products, many of which are hazardous or toxic. As a consequence of these issues, amide formation is responsible for the generation of large quantities of chemical waste.Commonly, amidation reagents provide a method for activating a carboxylic acid in order to make it sufficiently reactive towards an amine to form the desired amide. In theory, the same process can be achieved using a catalyst with removal of a molecule of water as a byproduct. Whilst some progress has been made on the identification of efficient catalysts for amide synthesis, such methods have failed to become widely adopted as a consequence of the fact that they are often less efficient than the existing approaches using reagents - usually because the catalytic methods require larger quantities of solvent in both the reaction and work-up procedure. A further limitation of most amidation catalysts is that they are fairly limited in scope in terms of the amides they can be used to prepare.We have recently reported the most efficient catalytic amidation reaction yet developed, and demonstrated that it can be applied to the multigram synthesis of some industrially relevant molecules. The aim of this project is to develop a detailed mechanistic understanding of this reaction, and to use that to design novel, readily accessible, and effective catalysts for amidation which can be applied in almost any amide synthesis. We will also identify efficient procedures for their use which can enable them to become widely adopted as the 'go to' method for making an amide in any organic chemistry laboratory. We will employ experimental and computational approaches to obtain a detailed mechanistic understanding of catalytic amidation reaction pathways, and use this understanding to design the new catalysts and procedures. Furthermore, we will develop a comprehensive 'user guide' to catalytic amidation which should enable any chemist to rapidly identify the best catalyst and procedure for a particular amidation reaction, facilitating the uptake of these reactions throughout the global chemistry community and leading to large reductions in chemical waste.

酰胺官能团的形成是在学术实验室和化学工业中合成有机分子的最常见过程之一。尽管存在许多有效的方法，但所有广泛使用的方法都需要使用效率低下的试剂，这些试剂产生大量废物，其中许多是危险或有毒的。由于这些问题的结果，酰胺形成是造成大量化学废物的产生的原因。毫无疑问，胺化试剂提供了一种激活羧酸的方法，以使其足以对胺形成所需的酰胺。从理论上讲，可以使用催化剂去除水分子作为副产品来实现相同的过程。尽管在鉴定酰胺合成的有效催化剂方面已经取得了一些进展，但由于它们通常比使用试剂的现有方法效率较低的结果，因此这种方法未能被广泛采用 - 通常是因为催化方法需要更大的方法反应和检查程序中的溶剂量。大多数胺化催化剂的进一步限制是，它们在可以用于准备的酰胺方面的范围相当限制。我们最近报告了尚未开发的最有效的催化酰胺反应，并证明可以将其应用于多gram某些与工业相关的分子的合成。该项目的目的是对这种反应进行详细的机械理解，并将其用于设计新颖，易于访问和有效的催化剂以胺化，这几乎可以应用于任何酰胺合成中。我们还将确定其使用的有效程序，使它们能够被广泛采用，作为在任何有机化学实验室中制造酰胺的“去”方法。我们将采用实验和计算方法来获得对催化酰化反应途径的详细机械理解，并使用此理解来设计新的催化剂和程序。此外，我们将开发全面的“用户指南”，以使任何化学家能够迅速确定特定障碍反应的最佳催化剂和程序，从而促进整个全球化学界对这些反应的吸收，并导致大量降低。化学废物。