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University of Bath PHD Novel Approaches to Catalytic Acyl Transfer Reactions Chhatwal, Amarjit Award date: 2015 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 04. Oct. 2021 Novel Approaches to Catalytic Acyl Transfer Reactions Amarjit Rosie Chhatwal A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Chemistry April 2015 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with the author. A copy of this thesis has been supplied on the condition that anyone who consults it is understood to recognise that its copyright rests with the author and they must not copy it or use material from it except as permitted by law or with the consent of the author. This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purposes of consultation effective from............................. Signed on behalf of the Faculty of Science.......................... Contents Acknowledgements ............................................................................................................. 3 Abbreviations ...................................................................................................................... 4 Abstract .............................................................................................................................. 6 Chapter 1: Amide Bond Formation from Carboxylic Acids and Amines ............. 7 Amide bond formation from carboxylic acids .................................................................. 8 The thermal (uncatalysed) formation of amides .............................................................. 9 Amide bond formation from carboxylic acids using activating/coupling agents .............. 11 Catalysed amide bond formation from carboxylic acids and amines .............................. 14 Homogeneous Catalysis ............................................................................................. 14 Heterogeneous catalysts ........................................................................................... 22 Summary ................................................................................................................... 24 Chapter 1: Results and Discussion 1 ............................................................................... 25 Aims .......................................................................................................................... 27 Nucleophilic additives................................................................................................ 28 More active zirconium complexes ............................................................................. 32 The removal of water ................................................................................................ 36 Conclusions ............................................................................................................... 43 Chapter 2: Alternative Acyl Donors-Esters, Ureas and Carbamates.................. 44 Alternative acyl donors.................................................................................................. 45 Esters in amide bond formation................................................................................. 45 Carbamates as Acyl Donors ....................................................................................... 52 Amides and ureas as acyl donors ............................................................................... 55 Summary ................................................................................................................... 65 Chapter 2: Results and Discussion 2 ............................................................................... 67 Aim ........................................................................................................................... 67 Esters as Acyl Donors ................................................................................................. 68 Ureas......................................................................................................................... 71 Carbamates as Acyl Donors ....................................................................................... 77 Alternative Carbamate Reactions .............................................................................. 84 Discussion ................................................................................................................. 87 Conclusions ............................................................................................................... 90 Future Work .............................................................................................................. 91 1 Chapter 3: Synthesis of Primary Amides from Carboxylic Acids................................ 92 Catalytic Methods ......................................................................................................... 94 Chapter 3: Results and Discussion ...................................................................... 99 Aim ........................................................................................................................... 99 Ammonia source identification .................................................................................. 99 Catalyst identification .............................................................................................. 100 Reaction Optimisation ............................................................................................. 104 Substrate scope ....................................................................................................... 109 Alternative acyl donors ............................................................................................ 117 Mechanistic insights ................................................................................................ 120 Conclusions ............................................................................................................. 128 Future work ............................................................................................................. 129 Chapter 4: Experimental data .................................................................................. 131 References ................................................................................................................... 167 2 Acknowledgements I would firstly like to thank my supervisor, Professor Jonathan Williams for giving me the opportunity to carry out this PhD. I truly appreciate his guidance, advice, support and patience. I would especially like to thank Dr Liana Allen for all of her help at the start of my PhD; Dr James Walton for his advice and guidance during my first two years and Dr Patricia Marcé-Villa (Patri) for all of her advice during the final months of my PhD. I must also thank several people that have contributed to the work presented in this thesis. I will begin by thanking Ben Atkinson who carried out transamidation studies in collaboration with the studies I carried out and Dr James Walton who conducted kinetic studies that enhance the work presented in chapters 1 and 2. Additional thanks goes to Dominic van der Waals who continued studies that stemmed from the work in Chapter 2 and Lewis Cooper who carried out additional studies on Chapter 3. My colleagues in the Williams and Bull groups (past and present) have made my PhD experience particularly enjoyable. Firstly, my sincere thanks goes to Sarah, Ruth, Ben, Helen and Caroline, with whom I have spent the majority of my time with and who have made my time so memorable. I would like to thank my awesome dancing buddies, Helen and Caroline for their support, friendship and numerous amazing nights out. I would also like to give further acknowledgement to Ben Atkinson for all of his help, advice and friendship and for all of his time spent listening to me whinge and proof reading this thesis. A big thanks also goes to thank Ruth Lawrence (my weekend and working late buddy) for her continual support, advice and shoulder to cry on. Finally I would like to express my sincere gratitude to my truly amazing parents and both of my sisters, Sonia and Subrena, as without their constant support, care and advice I would not have made it this far. 3 Abbreviations °C Degrees Centigrade Å Angstrom Act Activated BEMP 2-tertbutylimino-2-diethylamino-1,3-dimethylperhydro- 1,3,2-phosphorine Bn Benzyl nBu Butyl 13C NMR Carbon 13 Nuclear magnetic resonance cat. Catalyst CDCl3 Deuterated chloroform conv.