Multivicinal fluorinated cyclohexanes, a new structural motif in organic chemistry

多邻位氟化环己烷，有机化学中的新结构基序

• 批准号: EP/H022651/1
• 负责人: David O'Hagan
• 金额: $ 40.48万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FH022651%2F1
• 关键词: Multivicinal; fluorinated; cyclohexanes; new; structural

This research programme aims to introduce hexafluorocyclohexanes (HFCH) and their derivatives as a novel motif in organic chemistry. There is a very sparce literature associated with vicinal hexafluorinated cyclohexanes. They have hardly been studied. However there are indications that this motif could impart attractive and important properties and if synthesis routes could be established this would open up a new and high impact area in organic chemistry. Our recent synthesis focus on the preparation of acyclic multivicinal fluorinated compounds lays a good synthesis and analysis foundation for this programme. In essence we want now to synthesise the all-syn 1,2,3,4,5,6-hexafluorocyclohexane (all-synHFCH) as the flagship molecule of this research proposal, but alongside this, to explore chemistry around this molecule and access diastereoisomers and derivatives for functionalisation and utility.Theory studies indicate that all-synHFCH is a highly polar molecule. It has never been made before and there are only three references in the entire literature discussing this compound. A theory study in 2004, a Japanese patent (no structures isolated) and a an intriguing report from chemists in 1969. These chemist were fluorinating benzene using elemental fluorine (F2) and CoF3/KH and they isolated a solid fraction which they concluded from NMR and mass spec data was the all-trans isomer of HFCH. They also concluded that this isomer was chemically stable, although the particular isomer they had was conjecture. This is the only synthesis reported. The theory study in 2004 predicted highly polar molecules, especially for all-synHFCH. It had a predicted dipole moment of about 8.03 Debey. We also carried out a theory studies in preparation for this proposal and have evaluated an electrostatic surface map of all-syn HFCH which shows a +ve face and a -ve face to the molecule. Calculations also predict that that the molecules will stack, one on top of the other. If this is the case this compound and its steroisomers will have interesting solid state and liquid crystalline behaviour. So this becomes a particualry attractive structural motif, yet been explored by chemists.With this background the research programme will investigate the controlled synthesis of HFCH isomers and evaluate their properties (X-ray, NMR, DSC etc). We feel able to make these molecules because we have recently discovered methods for the stereoselective synthesis of acyclic vicinal fluorine motifs of upto five and six fluorines. That chemistry utilised epoxide ring opening reactions with HF reagents, and then fluorination reactions of the resultant fluorohydrins. So by applying our methods and expertise to cyclohexanetriepoxides, then there is an obvious route to HFCH's. Different diastereoisomers of the required triepoxides precursors are very well described in the literature, so we should be able to make good progress. We will also explore the preparation of ether and ester derivatives of 1,2,3,4,5-pentafluorocyclohexan-6-ols, such that this motif can be incorporated into larger molecular architectures. Candidate liquid crystal molecules and also long chain thiols which will be assessed by forming self assembling monolayers, have been identified as synthetic targets. We also identify tetrafluorocyclohexandiol monomers for polymerisation reactions, as a means of incorporating this novel motif into polymeris materials. The programme will be a success if we can develop routes to this new motif, characterise their general behaviour, and develop synthetic versitility such that it can be applied and demonstrated in a diversity of arenas.Funding for a trained postdoctoral researcher for three years, with appropriate consumables costs, is requested to develop this project and explore the outlined applications.

本研究计划旨在介绍六氟环己烷（HFCH）及其衍生物作为有机化学中的一种新的基序。有一个非常稀疏的文献与连位六氟化环己烷。他们几乎没有被研究过。然而，有迹象表明，这种基序可以赋予有吸引力的和重要的性质，如果合成路线可以建立，这将开辟一个新的和高影响力的有机化学领域。我们最近的合成重点是制备无环多乙烯基含氟化合物，为这一计划奠定了良好的合成和分析基础。本质上，我们现在想合成全顺式1，2，3，4，5，6-六氟环己烷（all-synHFCH）作为本研究提案的旗舰分子，但同时，探索围绕该分子的化学，并获得非对映异构体和衍生物的功能化和实用性。理论研究表明，all-synHFCH是一种高极性分子。它以前从未被提出过，在整个文献中只有三个参考文献讨论了这种化合物。2004年的理论研究，日本专利（没有分离出结构）和1969年化学家的一份有趣的报告。这些化学家使用元素氟（F2）和CoF 3/KH对苯进行氟化，他们分离出一种固体部分，根据核磁共振和质谱数据得出结论，该固体部分是HFCH的全反式异构体。他们还得出结论，这种异构体是化学稳定的，尽管他们拥有的特定异构体是推测的。这是唯一的合成报告。2004年的理论研究预测了高极性分子，特别是全合成HFCH。它的预测偶极矩约为8.03德贝。我们还进行了理论研究，为这一建议做准备，并评估了静电表面图的全合成HFCH，它显示了一个+ve面和一个-ve面对的分子。计算还预测，分子将堆叠，一个在另一个的顶部。如果是这种情况，则该化合物及其立体异构体将具有令人感兴趣的固态和液晶行为。在此背景下，本研究计划将研究HFCH异构体的可控合成，并评估其性质（X射线，NMR，DSC等）。我们感到能够制造这些分子，因为我们最近发现了立体选择性合成多达五个和六个氟的无环邻位氟基序的方法。该化学利用了与HF试剂的环氧化物开环反应，然后将所得氟代醇进行缩合反应。因此，通过将我们的方法和专业知识应用于环己烷三环氧化物，那么就有一条明显的路线可以获得HFCH。所需的三环氧化物前体的不同非对映异构体在文献中有很好的描述，因此我们应该能够取得良好的进展。我们还将探索1，2，3，4，5-五氟环己-6-醇的醚和酯衍生物的制备，使得该基序可以并入更大的分子结构中。候选液晶分子和长链硫醇，将通过形成自组装单层评估，已被确定为合成目标。我们还确定了用于聚合反应的四氟环己二醇单体，作为将这种新的基序并入聚合物材料的手段。该计划将是一个成功的，如果我们能够开发路线，以这种新的主题，他们的一般行为，并开发合成的versitivility，使它可以应用和展示在一个多样化的arenas.Funding为受过训练的博士后研究人员三年，与适当的消耗品成本，要求开发这个项目，并探讨概述的应用。

项目成果

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs).

• DOI: 10.3762/bjoc.10.307
• 发表时间: 2014
• 期刊: Beilstein journal of organic chemistry
• 影响因子: 2.7
• 作者: Adamkiewicz M;O'Hagan D;Hähner G
• 通讯作者: Hähner G

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane.

• DOI: 10.3762/bjoc.11.287
• 发表时间: 2015
• 期刊: Beilstein journal of organic chemistry
• 影响因子: 2.7
• 作者: Ayoup MS;Cordes DB;Slawin AM;O'Hagan D
• 通讯作者: O'Hagan D

Density Functional Study of Interactions between Fluorinated Cyclohexanes and Arenes

氟化环己烷与芳烃相互作用的密度泛函研究

• DOI: 10.1002/hlca.201400049
• 发表时间: 2014
• 期刊: Helvetica Chimica Acta
• 影响因子: 1.8
• 作者: Cormanich R

Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent

• DOI: 10.1016/j.jfluchem.2015.08.003
• 发表时间: 2015-11-01
• 期刊: JOURNAL OF FLUORINE CHEMISTRY
• 影响因子: 1.9
• 作者: Bykova, Tetiana;Al-Maharik, Nawaf;O'Hagan, David
• 通讯作者: O'Hagan, David