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Title: Electrochemical reduction of amides and c=c bonds
Author: Rix, Kathryn
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Reduction of amides to amines is an important transformation in organic synthesis, which has been identified as among the 'top ten most important reactions' by a consortium of pharmaceutical companies. Presently achieved by hydride or borane reagents, it is both hazardous and generates excessive volumes of effluent and waste. Similarly, chemoselective reduction of C=C bonds, particularly conjugated double bonds, also presents a significant challenge in organic synthesis. Electrochemical synthesis using a flow reactor offers an environmentally benign and energy efficient technology for producing key intermediates in the synthesis of candidate drug molecules; its benefits include: improved control of reaction parameters, reproducibility and scalability. The first part of the thesis describes a study on the kinetics of the selective electrochemical reduction of C=C maleimide derivatives using a rotating disc electrode system. The resulting data was used to define the reactor's operating conditions. Subsequently, the chemoselective and stereoselective reduction of maleimide derivatives were carried out in the electrochemical flow reactor with a graphite felt cathode and the rate of reactant depletion, monitored by UV-visible spectroscopy. In the second part, amide reduction was studied in an electrochemical flow reactor using vitreous carbon and boron-doped diamond cathodes. The reduction of N,N- dimethylbenzamide produced the corresponding amine, benzaldehyde and benzyl alcohol. The selectivity of the reaction was investigated as a function of reaction conditions, and a mechanism for the reduction was proposed. Subsequently, a range of functionalised amides were subjected to electrochemical reduction under optimised conditions, to further assess the scope of the methodology as a tool for organic synthesis. The influence of electron donating and withdrawing groups incorporated in to N-benzoylpyrrolidine derivatives were investigated, as well as the pattern of substitution on the amides. The result revealed observable trends in the product distribution between the corresponding amine, benzaldehyde and benzyl alcohol compounds.
Supervisor: Hellgardt, Klaus ; Hill, Mimi Sponsor: Pfizer Ltd ; GlaxoSmithKline ; Engineering and Physical Sciences Research Council ; Astra Zeneca
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available