Exploring the synthetic utility of 2,3,3,3-tetrafluoropropene

Lead Research Organisation: Durham University
Department Name: Chemistry

Abstract

Recently there has been an increased interest in the synthesis of trifluoromethylated organic compounds and several compounds with this substructure are in late stage development at GSK. The large scale synthesis of most CF3 containing compounds relies on the availability of a small number of inexpensive building blocks that are manufactured by halogen exchange reaction of chlorinated hydrocarbons with HF or by reacting carboxylic acids with SF4. In 2008, 2,3,3,3-tetrafluoropropene (HFO 1234yf) was introduced as a new, non-ozone depleting refrigerant gas with low global warming potential (GWP = 4) and atmospheric lifetime (11 days) and this material is now manufactured on industrial scale. Despite its availability, this compound has not found widespread applications in organic synthesis.

In this project the use of HFO 1234yf for the synthesis of various polyfunctional trifluoromethylated compounds is investigated. There are precedents in the literature to the Diels-Alder reaction of 3,3,3-trifluoropropene, therefore, it is reasonable to assume that HFO 1234yf will also undergo this reaction with various dienes. Treatment of the Diels-Alder adduct of an a-haloolefin and furan with base is known to afford 3-substituted phenol derivatives indicating the potential success of this proposed methodology. This strategy also provides several opportunities at introducing further functionalities, for example, by using metathesis and Heck reactions, that have also been demonstrated on 3,3,3-trifluoropropene.

The initial 6 months of the project could be a proof of concept study involving batch evaluation of the Diels-Alder reaction of HFO 1234yf with furan derivatives to better understand the reactivity of this compound. This could be performed in standard batch pressure equipment and if successful, can potentially be transferred to continuous flow. After synthesising a small number of furan Diels-Alder adducts the viability of the aromatisation stage can also be assessed to complete the proof-of-concept stage of the project.

In later stages, the substrate scope could be expanded by varying the substituents on either the furan ring or on the HFO 1234yf double bond. In case of successful implementation of this methodology in continuous flow, it would be interesting to evaluate the scaleability of the process on one or more pipeline related target molecules. An optimised reaction could also be used for sustainability assessment of this methodology, comparing it with alternative manufacturing routes.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R512527/1 01/10/2017 30/09/2021
1915208 Studentship EP/R512527/1 01/10/2017 30/09/2021 Ben Murray