A study into the use of ephedrine, immobilised on a silica support and its use in asymmetric alkynylation reactions

Shah, Beena (2015) A study into the use of ephedrine, immobilised on a silica support and its use in asymmetric alkynylation reactions. (PhD thesis), Kingston University, .

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Abstract

This work describes the preparation of an immobilised ephedrine silica supported catalyst and its application in asymmetric synthesis. (1R,2S)-(-)-Ephedrine is a controlled substance, whose use in synthesis is closely monitored by a licence regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). One way of reducing the demand for controlled substances as catalysts is to tether them onto a support medium so that after use they may be recovered by filtration, washed and reactivated, if necessary, dried and then reused. In this project, (1R,2S)-(-)-ephedrine was tethered onto a functionalised silica support and tested for its use in asymmetric alkynylation reactions involving a range of aromatic aldehydes and a terminal alkyne, phenylacetylene. The loading of the ephedrine on the supported catalyst was characterised by both elemental analysis and thermogravimetric analysis (TGA) due to the nature of the support material. The immobilised ephedrine catalyst was evaluated in asymmetric alkynylation reactions and was shown to provide good enantioselectivity (up to 92% for (R)-(+)-1,3-diphenylprop-2-yn-l-ol) and high yields for the secondary propargylic alcohols (up to 97%). The use of the immobilised ephedrine catalyst in asymmetric alkynylation reactions was assumed to be novel. The results of the newly formed secondary propargylic alcohols proved to be comparable to those achieved by homogeneous systems. The secondary propargylic alcohols were analysed using a wide range of spectroscopic techniques such as nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), optical rotation and high performance liquid chromatography (HPLC). Due to the restrictions placed on ephedrine, it was important to test the recyclability of the tethered catalyst to reduce the amount of the regulated drug in circulation. The catalyst demonstrated the ability to be recovered quantitatively from the reaction mixture using a simple filtration and then recycled in further asymmetric alkynylation reactions for three cycles before the yield was affected. In addition to the study, a novel tethering of ephedrine derivatives onto a silica support was investigation and its use in asymmetric alkynylation reactions explored. This was undertaken in an effort to optimise and improve upon the results obtained from N-methylephedrine alone. Our initial results showed that it is possible to tether ephedrine derivatives onto a silica support and then employ them in asymmetric synthesis, thus opening up the possibility to use controlled ephedrine more efficiently.

Item Type: Thesis (PhD)
Physical Location: This item is held in stock at Kingston University library.
Research Area: Chemistry
Pharmacy
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Pharmacy and Chemistry
Depositing User: Niki Wilson
Date Deposited: 04 Aug 2015 15:04
Last Modified: 06 Nov 2018 10:16
URI: http://eprints.kingston.ac.uk/id/eprint/32206

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