Catalytic approaches to the synthesis of amide bonds

  • Liana Allen

Student thesis: Doctoral ThesisPhD

Abstract

This thesis outlines work carried out in the last three years concerning the development of novel, atom-economic, catalytic syntheses of amide bonds, determination of the ranges of these reactions through substrate screenings and investigations into the mechanisms by which the reactions are operating.In Chapter 1, an introduction to amide bonds is given, after which a discussion on the synthesis of amide bonds is presented, covering direct coupling methods, enzymatic methods and both non-metal catalysts and metal catalysts used for amide bond synthesis. In the Results and Discussion section, an iron catalysed coupling of nitriles and amines is presented in Chapter 2. In Chapter 3, firstly the development of an indium and zinc catalysed rearrangement of aldoximes into primary amides is discussed, followed by development of a novel, nickel catalysed coupling of aldehydes and amines. Detailed mechanistic studies using 18O labelled substrates are then presented for both of these reactions. Chapter 4 details work on a novel, hydroxylamine hydrochloride catalysed transamidation of primary amides with amines, including 1H NMR studies to attempt to elucidate the mechanism of the reaction. Finally, in Chapter 5, work investigating the direct coupling of unactivated carboxylic acids and amines is discussed, followed by an investigation into suitable catalysts to improve the efficiency of the reaction and a comparison of the rates in the catalysed and uncatalysed reactions for a wide range of substrates.In the Results and Discussion section, an iron catalysed coupling of nitriles and amines is presented in Chapter 2.In Chapter 3, firstly the development of an indium and zinc catalysed rearrangement of aldoximes into primary amides is discussed, followed by development of a novel, nickel catalysed coupling of aldehydes and amines. Detailed mechanistic studies using 18O labelled substrates are then presented for both of these reactions.Chapter 4 details work on a novel, hydroxylamine hydrochloride catalysed transamidation of primary amides with amines, including 1H NMR studies to attempt to elucidate the mechanism of the reaction.Finally, in Chapter 5, work investigating the direct coupling of unactivated carboxylic acids and amines is discussed, followed by an investigation into suitable catalysts to improve the efficiency of the reaction and a comparison of the rates in the catalysed and uncatalysed reactions for a wide range of substrates.
Date of Award1 Feb 2012
Original languageEnglish
Awarding Institution
  • University of Bath
SponsorsEngineering and Physical Sciences Research Council
SupervisorJonathan Williams (Supervisor)

Keywords

  • catalytic
  • synthesis
  • amides

Cite this

Catalytic approaches to the synthesis of amide bonds
Allen, L. (Author). 1 Feb 2012

Student thesis: Doctoral ThesisPhD