University of Bath PHD Indium catalysed electrophilic aromatic substitution Hartley, Joseph P. Award date: 2002 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: 06. Oct. 2021 INDIUM CATALYSED ELECTROPHILIC AROMATIC SUBSTITUTION Submitted by Joseph P. Hartley For the Degree of PhD Of the University of Bath 2002 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without prior written 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. UMI Number: U153865 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U153865 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 | L:::;V!3R3iT OF BATH jj LiSRARY Ho - 5 pED ZG03 Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath INDIUM CATALYSED ELECTROPHILIC AROMATIC SUBSTITUTION II Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath CONTENTS CONTENTS III - IV ABBREVIATIONS V - VII ACKNOWLEDGEMENTS VIII ABSTRACT X CHAPTER 1: INTRODUCTION 1 1.1 Indium and its Applications 1 1.2 Indium(III) Salts in Organic Reactions 2 1.3 Conclusion 37 CHAPTER 2: ACYLATION AND SULFONYLATION 38 2.1 Acylation 39 2.1.1 Indium(III) Catalysed Acylation of Anisole 43 2.1.2 Acyl Donors 52 2.1.3 Aromatic Substrates 54 2.2 Benzoylation 58 2.2.1 Indium(III) Catalysed Benzoylation 58 2.3 Sulfonylation 61 2.3.1 Indium(III) Catalysed Sulfonylation 64 2.4 Mechanistic Aspects 70 III Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath CHAPTER 3: NITRATION 77 3.1 Introduction 78 3.2 Indium Triflate in Aromatic Nitration 83 3.3 Indium Triflamide in Aromatic Nitration 87 3.4 Mechanistic Aspects 88 CHAPTER 4: SULFAMOYLATION 91 4.1 Introduction 92 4.2 Catalytic Sulfamoylation 95 4.2.1 Indium Triflate in Sulfamoylation 100 4.2.2 Mechanistic Aspects 103 CHAPTER 5: CONCLUSION AND FURTHER WORK 104 CHAPTER 6 : EXPERIMENTAL 112 6 .1 General Experimental 113 6.2 Acylation of Aromatics 115 6.3 Benzoylation of Aromatics 120 6.4 Sulfonylation of Aromatics 126 6.5 Nitration of Aromatics 136 6.6 Sulfamoylation of Aromatics 141 6.7 Indium bis(perfluorooctanesulfonyl)amide 152 CHAPTER 7: REFERENCES 156 IV Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath ABBREVIATIONS Ac acyl acac acetoacetate Aq. aqueous A t aryl Bn benzyl BTF trifluorotoluene Bu butyl CDCI3 deuterated chloroform CTf3 tris(trifluoromethanesulfonyl)methide d doublet DCE 1,2 -dichloroethane DCM dichloromethane Et ethyl EtOAc ethyl acetate ee enatiomeric excess equiv. Equivalent FAB Fast Atom Bombardment h hour HQD hydroxyquinuclidine Hz Hertz J coupling constant LA Lewis acid m meta m multiplet v Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath Me methyl MeCN acetonitrile MeOH methanol mol. molecular NMR nuclear magnetic resonance NTf2 bis(trifluoromethanesulfonyl)amide Nuc nucleophile o ortho OMe methoxy OTf trifluoromethanesulfonate ONf nonafluorobutanesulfonate p para Ph phenyl Pr propyl ppm parts per million rt room temperature s singlet Sat. saturated SDS sodium dodecylsulfate t triplet TBDMS rm-butyldimethylsilyl Tf trifluoromethanesulfonyl THF tetrahydrofuran TLC thin layer chromatography TMS trimethylsilyl VI Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath Tol tolyl Ts tosyl q quartet VII Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath ACKNOWLEDGEMENTS I would like to thank my supervisor, Chris Frost, for all his enthusiasm, encouragement, ideas and advice for the duration of my PhD; he has been an excellent mentor and has made my time in his group enjoyable and productive. I would also like to thank my industrial supervisors Alan Whittle and David Griffin for their welcomed advice, for the chance to work at Jealott’s Hill and for the financial support of this project. I would like to thank my fellow Frost group members, Paul, Christelle, Kam, Cath, Chris, Kelly and Steve. Thanks also go to all the postgraduate chemists at the Department of Chemistry, for making it such an enjoyable place to work. I am indebted to Chris, Phill, Phil, Mike, Steve F and Rudy Jazzar for technical assistance, and to all my proof readers. Special thanks goes to Yvonne and Malcolm, to Matt Dolan for his kind help when I broke my collarbone, and to my team mates in the Chem/Admin soccer team, at the University of Bath R.F.C. and at Stothert and Pitt R.F.C. for providing an enjoyable distraction from chemistry. I would like to thank my parents, and my brothers Chris, Nick, Pat and Benji for their help and support through the last 3 years. Thanks also for the loan of the PC, which was of invaluable help in producing this work. Finally, my deepest gratitude goes to Amanda, for all her love, support and encouragement that has been vital over the last three years. You’re a star. VIII Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath Dedicated to Mum, Dad and the boys IX Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath ABSTRACT The catalytic efficacy of indium(III) salts, including indium triflate and the novel complex indium triflamide, has been investigated in a number of electrophilic aromatic substitution reactions. Lower catalyst loadings, a wider scope of substrates and higher yields have been achieved with respect to other Lewis acids. The Friedel-Crafts acylation of electron rich aromatics has been achieved in high yield using a potent combination of indium and lithium salts. Indium salts have also been found to be exceptional catalysts for Friedel-Crafts benzoylation and sulfonylation reactions, furnishing the corresponding diaryl ketones and sulfones in high yield. Indium triflate is among the most efficient catalysts reported for these reactions. Indium complexes have also been employed successfully as catalysts for aromatic nitrations, replacing the use of concentrated sulfuric acid. The only side product is water and the catalysts may be recycled and reused, presenting an environmentally acceptable procedure. The reaction of aromatics with dialkyl sulfamoyl chlorides presents a facile route to aryl sulfonamides. Indium triflate was found to be the most efficient Lewis acid catalyst for this demanding process. X Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath CHAPTER 1 INTRODUCTION 1 Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath 1 Introduction 1.1 Indium and its Applications Until very recently the interest in indium and its applications lay in low melting-point alloys and solders, display devices and semiconductors. While boron or aluminium reagents have been the subject of considerable interest, the use of indium in organometallic reactions was limited, due, primarily, to its low natural abundance ( 0.1 ppm, comparable with silver) and the fact that organoindium compounds are less reactive than alkyllithiums and Grignard reagents. However, the discovery that indium metal can react with an organic substrate to generate an organoindium species in situ, means that the use of sensitive, toxic or expensive organometallics can be avoided. Thus, allylation, cyclopropanation and Reformatsky reactions can be affected using indium metal and the corresponding allyl halides, methylene dibromides and a-haloesters .1 Whilst indium is not unique in its ability to carry out such reactions (it is comparable with tin and zinc), its exceptional stability to water and air allows such reactions to be carried out under aqueous conditions. The associated practical advantages of water as a solvent has led to an explosion of interest in indium mediated processes .1,2 Recently, indium(III) complexes have received a great deal of interest as Lewis acid catalysts. Although comparatively weak when compared to their aluminium and boron counterparts, indium(III) salts are stable to water and are reusable. This introduction serves to detail the use of indium(III) salts as Lewis acids in organic synthesis. Joseph P. Hartley Indium Catalysed Electrophilic Aromatic Substitution University of Bath 1.2 Indium(III) Lewis acids in Organic Synthesis Transesterification of esters to the corresponding analogues with higher alcohol moieties is well documented, however the reverse transformations are not.