AA-STARR: Aromatic Amine Synthesis by Tapping Aminium Radical Reactivity

AA-STARR：利用铵自由基反应合成芳香胺

• 批准号: EP/R023492/1
• 负责人: Stephen Marsden
• 金额: $ 51.34万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR023492%2F1
• 关键词: AA; STARR; Aromatic; Amine; Synthesis

Aromatic amines are amongst the most important chemical motifs, featuring in functional molecules such as colourants, pharmaceutical drugs and agrochemicals. Indeed, the foundation of the modern chemical industry was driven in large part by the development of new dyestuffs based on aromatic amines in the 1850s. Despite the significance of aryl amines, methods for their production can still involve wasteful multi-step processes with noxious waste streams. More modern methods have been developed such as the so-called Buchwald-Hartwig coupling, but these require the use of pre-functionalised substrates (which carry their own waste inventory) and catalysts based upon the scarce precious metal palladium. In this work, we will develop methods to directly aminate aromatic rings using simple and cheap reagents in conjunction with light sources (ultra-violet and visible). The reactions exploit active species known as aminium radicals. Reactions of aminium radicals have been known for over 100 years, but they remain underexploited. We have recently developed ways to harness these reactive species to give highly productive amination of aromatics. Further, the reactivity allows us to access unusual molecular structures which will find applications in drug discovery and the preparation of fluorescent materials.Our objectives are to (i) create a suite of conditions to achieve the amination reactions; (ii) to demonstrate this in the creation of a wide range of novel molecules with diverse structures; (iii) develop a new variant in which the aromatic ring is 'destroyed' in the process, allowing access to very different products from the same type of starting materials. We will demonstrate non-academic impact of our work by making novel molecular 'building blocks' available to buy (through a project partner), and by creating a unique library of small molecules known as fragments which can be used for screening programmes in drug discovery.

芳香胺是最重要的化学基序之一，在功能分子如着色剂、药物和农用化学品中具有特征。事实上，现代化学工业的基础在很大程度上是由19世纪50年代基于芳香胺的新染料的开发所推动的。尽管芳香胺很重要，但其生产方法仍然可能涉及浪费的多步工艺和有毒废物流。已经开发了更现代的方法，例如所谓的Buchwald-Hartwig偶联，但这些方法需要使用预官能化的底物（其携带自己的废物库存）和基于稀缺贵金属钯的催化剂。在这项工作中，我们将开发方法，直接胺化芳香环使用简单，廉价的试剂结合光源（紫外线和可见光）。这些反应利用了被称为铵自由基的活性物质。铵自由基的反应已经知道了100多年，但它们仍然没有得到充分利用。我们最近开发了利用这些反应性物质的方法，以提供高产的芳烃胺化。我们的目标是（i）创造一套实现胺化反应的条件;（ii）证明这一点，在创造各种具有不同结构的新型分子中;（iii）在制备具有不同结构的新型分子中使用胺化反应。（iii）开发一种新的变体，其中芳环在该过程中被“破坏”，从而可以从相同类型的起始材料获得非常不同的产品。我们将展示我们的工作的非学术影响，使新的分子“积木”可供购买（通过项目合作伙伴），并通过创建一个独特的小分子库称为片段，可用于药物发现的筛选计划。