Synthesis of organic heterocycles via electroreductive cyclisations and the computational simulation of electrochemical reactors

Abstract

Organic electrochemical synthesis has become an exciting area of research within the chemical sciences. The ability to replace stoichiometric reductants and oxidants with electrons themselves, arguably the simplest of reagents possible, has led to a myriad of synthetic applications fuelled partially by the drive for greener chemistry. Furthermore, within the field of organic electrosynthesis the use of flow chemical reactors has become common due to the significant advantages these reactor designs possess over conventional batch electrolysis. This includes large electrode surface area to reactor volume ratios, leading to enhanced mass transport phenomena. Coupled with the ability to apply large currents through narrow interelectrode gaps, high conversion rates can be realised relatively easily. This thesis focuses on the reductive electrolysis of aryl halides resulting in the generation of aryl radicals. Key to this work is the use of electrochemical mediators. These species act as an electron shuttle from the electrode to the starting material resulting in a reaction layer that detaches from the electrode surface. This brings further advantages to electrosynthesis through an enhanced selectivity for the desired pathway by promoting single electron reductions and negating the effects of over-reduction. When propargylic bonds were appended in proximity to these electrogenerated aryl radicals through O or N linkages, cyclisations could be solicited affording aromatic heterocyclic products. With the use of the Ammonite 8 flow reactor this methodology was applicable for the synthesis of benzofurans, furopyridines and select examples of indoles and was easily scalable to multi-gram synthesis. The second part of this research investigates the development and impact of detached reaction layers in mediated electrosynthesis through computational electrochemistry. Here a numerical analysis solver, COMSOL Multiphysics, was employed to probe concentration profiles and product selectivity during electrolysis. This allowed the impact of parameters such as diffusion coefficients and mediator reduction potentials to be easily visualised. Simulations predicted that the establishment of detached reaction layers was key to successful syntheses and was dependent upon a complex interplay of the mass transport phenomena. This provides a novel proposal for the mechanism of mediated electrolysis that incorporates more factors than simple comparison of the mediator and substrate reduction potentials.

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Identifiers

ORCID for Jack William Hodgson: orcid.org/0000-0003-0597-3330

ORCID for Richard Brown: orcid.org/0000-0003-0156-7087

ORCID for David Harrowven: orcid.org/0000-0001-6730-3573

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