STUDIES ON SELECTIVELY FLUORINATED CYCLOALKANES Zeguo Fang A Thesis Submitted for the Degree of PhD at the University of St Andrews 2020 Full metadata for this item is available in St Andrews Research Repository at: http://research-repository.st-andrews.ac.uk/ Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/19999 This item is protected by original copyright Studies on selectively fluorinated cycloalkanes Zeguo Fang This thesis is submitted in partial fulfilment for the degree of Doctor of Philosophy (PhD) at the University of St Andrews February 2020 Acknowledgements First of all, I would like to say thank you to my supervisor, Prof. David O’Hagan, from the bottom of my heart. Although it has already been over 4 years, I can still clearly remember the first dialogue between David and me. David said, “St Andrews is a very nice and ancient University, and it is a good place to live and study.” Really thank you for giving me the opportunity to study in your group. Therefore, I have the chance to come to this beautiful and quiet town. I have covered every corner of St Andrews and already regarded it as my second home. More importantly, it is an absolutely great honour for me to work under your guidance. Without your constant encouragements and useful suggestions during my PhD career, I probably could not make any progress. At the same time, your keen interest to chemistry and rigorous research attitude deeply influenced me. I learnt those valuable characters from you and that is a treasure of my life. I would like to express my sincere thanks to China Scholarship Council (CSC). Without your funding support, I couldn’t study abroad and experience a different life. Thanks for all the staff in Education Section of the Embassy of the People’s Republic of China in the Unite Kingdom of Great Britain and Northern Ireland for your contribute so that I can study here safely and peacefully. I do wish you all the best! I have to express my hearty gratitude to my father and mother. I know I caused you a lot of troubles during my PhD career, but really thank you for your support, patience and understanding! I also want to express my thanks to Liyang Fan. Thank you for your accompany and I hope you can be happy in the coming days. IV There is no doubt that my research work can not be finished without many excellent scientists. Thanks to Mrs. Melanja Smith, Dr. Tomas Lebl and Dr. Siobhan Smith for the NMR analysis. My thanks are extended as well to Prof. Alex Slawin and Dr. David Cordes for X-ray analysis. The whole O’Hagan group (present and past) helped me a lot especially when I firstly arrived here. It is so happy to work and be friends with you guys. Particularly, I would like to mention Dr. Nawaf Al-Maharik for your daily guidance and assistance in the lab. Sometimes, we have different opinions on something, but it proves that you are always right. Dr Neil Keddie for your general knowledge; Dr. Qingzhi Zhang for your help both inside and outside the lab. As a colleague, but mostly as a friend, I wish you all the best in the future. I would like to offer my thanks to all my Chinese friends in St Andrews, including Lutao Zhang, Teng Li, Xuan Feng, Cihang Yu, Rongtian Suo, Shuangbin Li, Peng Ma, Meng Zhang, Chengfei Li, Shitao Wu, Jianing Hui and others. Many thanks for your accompany. Finally, I have to thank myself. Thank you for working hard and never giving up. It is not easy to get a PhD degree, but you successfully overcome all the obstacles during this journey. I do hope you can keep working hard and becoming a good person in the future! I gratefully acknowledge the EPSRC for funding (GR: EP/R013799/1) and the China Scholarship Council for PhD studentship support. V Abstract The thesis focuses on the synthesis of novel fluorinated cycloalkanes and their polar properties. Selected molecules are shown below: Chapter 2 describes the synthesis of all cis-1,2,3,4-tetrafluorocyclopentane and its deuterated isotopomer. They were prepared from the dicyclopentadiene. The structure of cis-1,2,3,4- tetrafluorocyclopentane was characterised by NMR and X-ray crystallography. This structure proved to have high polarity and a calculated dipole moment is 4.9 Debye. The deuterated isotopomer was also characterised by NMR and it indicated that this molecule has highly polarized faces similar to all cis-1,2,3,4-tetrafluorocyclopentane. The polarity of the isotopomers were compared by GC-MS analysis and this gave an indication that per-deuterated isotopomer is more polar than the all cis-1,2,3,4-tetrafluorocyclopentane. Chapter 3 describes the synthesis of a series of fluorinated cyclopropanes, with a particular focus on the preparation of the all cis-1,2,3-trifluorocyclopropane motif. The synthesis started from the fluorinated styrene, followed by bromofluocarbene (:CFBr) addition and reductive debromination. This provided the first synthetic access to this motif. The lipophilicity (Log P) of a series of fluorinated cyclopropanes was investigated and the results demonstrated that the all cis-1,2,3-trifluorocyclopropane was the most polar compound among this series. Chapter 4 describes unexpected results from the fluorination of benzo[a,e]cyclooctatetraene with NBS, HF·Py and AgF(I), which was anticipated to generate all-cis-5,6,11,12-tetrafluoro- 5,6,11,12-tetrahydrodibenzo[a,e]cyclooctane. However, the reaction gave a mixture of products and the product outcomes strongly suggests that an extensive carbocation/phenonium rearrangements pathway occurred during the reaction. The origin of oxygen in the final ether products was shown by an 18O isotope labelling experiment with water and the result suggests a {Ag}O- species is the most likely oxygen provider. Chapter 5 describes the synthesis of a series of novel liquid crystals with fluorinated cyclopropane motifs at their terminus. The synthesis proved straightforward such that these novel liquid crystal candidates can be prepared on scale. Their thermodynamic and physical properties, such as birefringence (Δn), dielectric anisotropy (Δε) and rotational viscosity (ϒ) were analysed by Merck & Co. Although none of the liquid crystal candidates met all the criteria for Liquid Crystal Display (LCD) development, the study gives an insight into the potential for fluorinated cyclopropane motifs in liquid crystals. VI Abbreviations Ac Acetyl group AIBN Azobisisobutyronitrile amu Atomic mass unit Bu Butyl group BuLi Butyllithium b.p. Boling point bs Broad singlet COD 1,5-cyclooctadiene CI Chemical ionisation D Debye d Doublet dd Doublet of doublets DAST Diethylaminosulfur trifluoride DBCOT Dibenzo[a,e]cyclooctatraene DCM Dichloromethane Deoxofluor Bis(2-methoxyethyl)amonosulfur trifluoride DFT Density functional theory DSC Differential scanning calorimetry En Vibrational energy e.e. Enantiomeric excess VII EI Electron impact equiv. Equivalent ESI Electrospray ionization Et Ethyl group Fluolead 4-Tertbutyl-2,6-dimethyl phenylsulfur trifluoride GC Gas chromatography HRMS High resolution mass spectrometry IR Infrared spectroscopy J Coupling constant m Multiplet mCPBA meta-Chloroperoxybenzoic acid Me Methyl group MHz Megahertz MOF Metal organic framework m.p. Melting point MS Mass spectrometry Δn Birefringence NBS N-Bromosuccinimide NDHPI N,N-Dihydroxypyromellitimide NMR Nuclear magnetic resonance POM Polarising optical microscope VIII ppm Parts-per-million PTFE Poly(tetrafluoroethylene) pTSA p-Toluenesulfonic acid r.t. Room temperature s Singlet SET Single electron transfer t Triplet TBAF Tetrabutylammonium fluoride Tf Triflyl (Trifluoromethanesulfonyl) TFA Trifluoroacetic acid THF Tetrahydrofuran TN Twisted nematic Ts Tosyl (Toluenesulfonyl) UV Ultraviolet VA Vertical alignment Xtalfluor Aminodifluorosulfinium tetrafluoroborate salts Δε Dielectric anisotropy ϒ Rotational viscosity IX Table of Contents Chapter 1. Introduction ......................................................................1 1.1 Background of fluorine ....................................................................................................................... 1 1.2 The properties of fluorine ................................................................................................................... 2 1.2.1 The physical properties of fluorine .............................................................................................. 2 1.2.2 The chemical properties of fluorine ........................................................................................... 10 1.3 Properties and effect of the C-F bond .............................................................................................. 11 1.3.1 Hyperconjugation and the ‘gauche’ effect ................................................................................ 11 1.3.2 Dipole–dipole interactions ......................................................................................................... 12 1.3.3 Charge–dipole interactions ........................................................................................................ 14 1.4 C-F Bond formation ........................................................................................................................... 15 1.4.1 Nucleophilic fluorination............................................................................................................ 15 1.4.2 Electrophilic fluorination............................................................................................................ 19 1.4.3 Radical fluorination ...................................................................................................................