Multivicinal fluorinated cyclohexanes, a new structural motif in organic chemistry
Lead Research Organisation:
University of St Andrews
Department Name: Chemistry
Abstract
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.
Planned Impact
Who will benefit? The research has the potential to impact on a number of industries providing technology driven products. Outstanding success, perhaps in 10 years time would provide products that would improve display technologies and health for society. The organic chemistry community. How will they benefit? They will benefit if the new structural motifs are realised and characterised are then utilised in the design and synthesis of novel performance molecules. What will be done? The research will be published in leading journals. Patenting and IPR protection will be required for societal impact. Methods of Communication and engagement Presentations will be made at key international conferences.This enables an ongoing and intensive discussion with the relevant international community. Collaboration and exploitation DO'H has a close relationship with key companies in organo-fluorine product development such as DuPont and Merck Liquid Crystals. They and others will become aware of the developments, and through such routes the impact of the research reaches front line industry in the relevant areas.
Organisations
People |
ORCID iD |
David O'Hagan (Principal Investigator) |
Publications
Adamkiewicz M
(2014)
Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs).
in Beilstein journal of organic chemistry
Ayoup MS
(2015)
Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane.
in Beilstein journal of organic chemistry
Bykova T
(2015)
Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent
in Journal of Fluorine Chemistry
Bykova T
(2016)
Multicomponent reactions of methyl substituted all-cis tetrafluorocyclohexane aldehydes.
in Organic & biomolecular chemistry
Cormanich R
(2014)
Density Functional Study of Interactions between Fluorinated Cyclohexanes and Arenes
in Helvetica Chimica Acta
Cormanich R
(2015)
Inter- and intramolecular CF···c?o interactions on aliphatic and cyclohexane carbonyl derivatives
in Journal of Computational Chemistry
Cormanich RA
(2015)
Particularly strong C-H···p interactions between benzene and all-cis 1,2,3,4,5,6-hexafluorocyclohexane.
in Physical chemistry chemical physics : PCCP
Durie A
(2012)
The Synthesis of ?-1,2,3,4,5,6-Hexafluorocyclohexane (Benzene Hexafluoride) from Benzene
in Angewandte Chemie International Edition
Durie AJ
(2014)
Stepwise preparation of all-cis 1,3,4-trifluoro-2-phenylcyclohexane, avoiding a phenonium intermediate.
in The Journal of organic chemistry
Keddie NS
(2015)
All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane.
in Nature chemistry
Description | We have prepared all-cis 1,2,3,4,5,6-hexafluorocyclohexane. This was a landmark molecule and emerges as among the most polar non-ionic organic compounds ever made. It has highly unusual properties which will be of interest to materials chemists and physicists |
Exploitation Route | This compound has prospects as a new motif for pharmaceuticals discover. For materiles it has attractive properties as a motif for the development of piezoelectric materials |
Sectors | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
URL | http://www.nature.com/nchem/journal/v7/n6/full/nchem.2232.html |
Description | Professor O'Hagan was awarded the Henri Moissan Medal and Prize in 2018. This Award is presented every 3 years to a scientist who has contributed most significantly to fluorine chemistry. It is Awarded by the French, Maison de la Chemie. Too early for this. Sample of the compound have been used in collaboration with Waterloo in Canada (ion association properties) and these have led to new papers. Theory collaborations are underway with a collaborator in Brazil. |
First Year Of Impact | 2017 |
Sector | Chemicals,Healthcare,Manufacturing, including Industrial Biotechology |
Impact Types | Cultural |