Reactions with Singlet Oxygen and Supercritical Fluids

与单线态氧和超临界流体的反应

• 批准号: EP/F015275/1
• 负责人: Martyn Poliakoff
• 金额: $ 41.11万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF015275%2F1
• 关键词: Reactions; Singlet; Oxygen; Supercritical; Fluids

This Proposal aims to develop a greener approach to the use of a highly reactive form of oxygen (singlet oxygen, 1O2) for reactions involving compounds of interest to the pharmaceutical and low-tonnage fine chemicals industries by exploiting several different properties of high pressure CO2 (scCO2) to address and overcome problems in existing 1O2 methodologies. The Proposal has been developed with the active participation of industrial partners, AstraZeneca and Thomas Swan & Co Ltd, both of whom have a record of effective collaboration with our research group.1O2 has a history of cleaner chemical synthesis which long predates the birth of Green Chemistry in the 1990s for example, with the German chemist Schenck's post-war synthesis of the medicinal compound ascaridole, reputedly with spinach leaves as the photosensitizer! From a green standpoint 1O2 has several attractions: (i) 1O2 has the potential to promote chemically useful transformations and (ii) 1O2 can be generated photochemically, sometimes even using sunlight, and only requires visible light rather than UV, thus avoiding problems of inadvertent generation of ozone. (iii) On grounds of both safety and atom efficiency, the photochemical generation of 1O2 is preferable to current thermal routes. 1O2 is additionally attractive for pharmaceutical process chemistry which has a pressing need for transformations that combine reduction in waste with complex chemistry. In particular, our Proposal targets two aspects of Green chemistry, formation of allylic alcohols, and safe use of O2 in non-chlorinated solvents, recently highlighted as being of specific importance to the pharmaceutical industry. Furthermore, the low tonnages in most pharmaceutical processes mean that the degree of scale-up required is less than in many sectors of the chemical industry.Our aim is to demonstrate the feasibility of continuous photochemical reactions of 1O2 in solvents expanded with CO2, so-called Gas-Expanded liquids, GXLs. The key will be to exploit the biphasic nature of the GXLs to maximize the efficiency not only of the reaction itself but also of the separation of the product and photosensitizer. Our strategy is to build a relatively small high pressure falling-film reactor, FFR, where the liquid flows down a plate thereby giving more precise control over reaction conditions. The design has been chosen to give us flexibility in the way that the reactor is configured (e.g. concurrent or counter-current flow, etc). Combining this flexibility with the modular nature of the high-pressure equipment available in Nottingham will allow us to modify our approach rapidly in response to our experimental results. A particular advantage of the design is that, in most cases, it will allow us to carry out control experiments in the absence of CO2 so that we can establish the precise effect of CO2 on a given reaction. Our chemical programme focuses on four classes of reactions chosen in consultation with our partners, specifically for their relevance to pharmaceutical process chemistry.

该提案旨在开发一种更环保的方法，通过利用高压二氧化碳的几种不同特性，使用高反应性氧气（单线态氧，1O2）进行涉及制药和小吨位精细化工行业感兴趣的化合物的反应（ scCO2）来解决和克服现有 1O2 方法中的问题。该提案是在阿斯利康 (AstraZeneca) 和托马斯·斯旺有限公司 (Thomas Swan & Co Ltd) 等工业合作伙伴的积极参与下制定的，这两家公司都有与我们的研究小组进行有效合作的记录。1O2 拥有清洁化学合成的历史，其历史早于绿色化学的诞生。以20世纪90年代的化学为例，德国化学家申克在战后合成了药用化合物ascaridole，据说以菠菜叶作为光敏剂！从绿色的角度来看，1O2 有几个吸引力：(i) 1O2 具有促进化学有用转化的潜力，(ii) 1O2 可以通过光化学方式生成，有时甚至使用阳光，并且只需要可见光而不是紫外线，从而避免了无意中产生的问题臭氧的产生。 (iii) 出于安全性和原子效率的考虑，光化学生成 1O2 优于当前的热途径。 1O2 对于制药过程化学也很有吸引力，制药过程化学迫切需要将废物减少与复杂化学相结合的转变。特别是，我们的提案针对绿色化学的两个方面，烯丙醇的形成以及在非氯化溶剂中安全使用氧气，最近强调这对制药行业特别重要。此外，大多数制药工艺中的低吨位意味着所需的放大程度低于化学工业的许多部门。我们的目标是证明 1O2 在用 CO2 膨胀的溶剂中进行连续光化学反应的可行性，因此 -称为气体膨胀液体，GXL。关键是要利用 GXL 的双相性质，不仅最大限度地提高反应本身的效率，而且最大限度地提高产物和光敏剂的分离效率。我们的策略是建造一个相对较小的高压降膜反应器（FFR），液体沿着板流下，从而更精确地控制反应条件。选择该设计是为了让我们能够灵活地配置反应器（例如顺流或逆流等）。将这种灵活性与诺丁汉可用的高压设备的模块化性质相结合，将使我们能够根据实验结果快速修改我们的方法。该设计的一个特殊优点是，在大多数情况下，它允许我们在没有 CO2 的情况下进行控制实验，以便我们可以确定 CO2 对给定反应的精确影响。我们的化学计划侧重于与我们的合作伙伴协商后选择的四类反应，特别是它们与制药工艺化学的相关性。

项目成果

Homogeneous photochemical oxidation via singlet O2 in supercritical CO2.

在超临界 CO2 中通过单线态 O2 进行均相光化学氧化。

• DOI: 10.1039/b806063k
• 发表时间: 2008-09-18
• 期刊: Chemical communications
• 影响因子: 4.9
• 作者: R. Bourne;Xue Han;Adrian O. Chapman;Nicholas J. Arrowsmith;H. Kawanami;M. Poliakoff;M. George
• 通讯作者: M. George

Cleaner continuous photo-oxidation using singlet oxygen in supercritical carbon dioxide.

使用超临界二氧化碳中的单线态氧进行更清洁的连续光氧化。

• DOI: 10.1002/anie.200901731
• 发表时间: 2009-07-06
• 期刊: Angewandte Chemie
• 作者: R. Bourne;Xue Han;M. Poliakoff;M. George
• 通讯作者: M. George

Immobilised photosensitisers for continuous flow reactions of singlet oxygen in supercritical carbon dioxide

用于超临界二氧化碳中单线态氧连续流动反应的固定化光敏剂

• DOI: 10.1039/c0sc00641f
• 发表时间: 2011-06-01
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Xue Han;R. Bourne;M. Poliakoff;M. George
• 通讯作者: M. George

Maximising the efficiency of continuous photo-oxidation with singlet oxygen in supercritical CO2 by use of fluorous biphasic catalysis.

通过使用氟双相催化，最大限度地提高超临界 CO2 中单线态氧的连续光氧化效率。

• DOI: 10.1039/c2cc17429d
• 发表时间: 2012-02-27
• 期刊: Chemical communications
• 影响因子: 4.9
• 作者: Jessica F. B. Hall;Xue Han;M. Poliakoff;R. Bourne;M. George
• 通讯作者: M. George

Real-time product switching using a twin catalyst system for the hydrogenation of furfural in supercritical CO2.

• DOI: 10.1002/anie.201005092
• 发表时间: 2010-11-15
• 期刊: Angewandte Chemie
• 作者: James G. Stevens;R. Bourne;M. Twigg;M. Poliakoff
• 通讯作者: M. Poliakoff