Functional Cage-Amine Complexes: Polymerisable Metallomonomers and Multi-Cage Complexes By Nigel Andrew Lengkeek B. Sc. (Hons) B.E. (Hons) This thesis is presented for the degree of Doctor of Philosophy of The University of Western Australia, Discipline of Chemistry, School of Biomedical, Biomolecular and Chemical Sciences, December 2007. ………..…………….. Nigel A. Lengkeek DECLARATION FOR THESES CONTAINING PUBLISHED WORK AND/OR WORK PREPARED FOR PUBLICATION 1 This thesis does not contain work that I have published, nor work under consideration for publication. The thesis is completely the result of my own work, and was substantially conducted during the period of candidature, unless otherwise stated in the thesis. Signature………………………………. 22 This thesis contains sole-authored published work and/or work prepared for publication. The bibliographic details of the work and where it appears in the thesis is outlined below. Signature……………………………… 3 This thesis contains published work and/or work prepared for publication, some of which has been co- authored. The bibliographic details of the works and where they appear in the thesis are set out below. (The candidate must attach to this declaration a statement detailing the percentage contribution of each author to the work. This must been signed by all authors. Where this is not possible, the statement detailing the percentage contribution of authors should be signed by the candidate’s Coordinating Supervisor). The Following chapters contain work that is being prepared for publication: Chapter 2 & 3: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Cinnamyl functionalised Cage Amine Complexes: Synthesis, Structure and Copolymerisation’, Manuscript in Preparation J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Styryl functionalised Cage Amine Complexes: Synthesis, Structure and Copolymerisation’, Manuscript in Preparation J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Reactivity of Cinnamyl-Cage-Amine Complexes with Reducing Agents: Cleavage and Reduction to Phenylpropyl-Cage-Amine Derivatives’, Manuscript in Preparation Chapter 4: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Thiophene Derivatives of Cage Amines: Synthesis, Structure and Electrochemistry’, Manuscript in preparation J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, ‘Synthesis and Electropolymerisation of N- (4’-carboxybenzene)-2,5-di(2’’-dithienyl)pyrrole’, Manuscript in preparation Chapter 5: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Electronic communication is a simple p-xylyl-bis-cage-amine complex’, Manuscript in Preparation Signature……………………………… Statement of Candidate Contribution Chapter 2 & 3: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Cinnamyl functionalised Cage Amine Complexes: Synthesis, Structure and Copolymerisation’, Manuscript in Preparation JMH (5 %), GAK (10 %), NAL (75 %), BWS (5 %), AHW (5 %) J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Styryl functionalised Cage Amine Complexes: Synthesis, Structure and Copolymerisation’, Manuscript in Preparation JMH (5 %), GAK (10 %), NAL (75 %), BWS (5 %), AHW (5 %) J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Reactivity of Cinnamyl-Cage-Amine Complexes with Reducing Agents: Cleavage and Reduction to Phenylpropyl-Cage-Amine Derivatives’, Manuscript in Preparation JMH (5 %), GAK (10 %), NAL (75 %), BWS (5 %), AHW (5 %) Chapter 4: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Thiophene Derivatives of Cage Amines: Synthesis, Structure and Electrochemistry’, Manuscript in preparation JMH (5 %), GAK (10 %), NAL (70 %), BWS (10 %), AHW (5 %) J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, ‘Synthesis and Electropolymerisation of N-(4’-carboxybenzene)-2,5-di(2’’-dithienyl)pyrrole’, Manuscript in preparation JMH (5 %), GAK (10 %), NAL (85 %) Chapter 5: J. M. Harrowfield, G. A. Koutsantonis, N. A. Lengkeek, B. W. Skelton & A. H. White, ‘Electronic communication is a simple p-xylyl-bis-cage-amine complex’, Manuscript in Preparation JMH (5 %), GAK (10 %), NAL (70 %), BWS (10 %), AHW (5 %) We hereby declare that the individual authors, or corresponding authors, have granted permission to the candidate (Nigel A. Lengkeek) to use the results presented in the manuscripts in this thesis. ……….……….……….………. ……….……….……….………. Nigel Lengkeek Dr. George A. Kousantonis (PhD Candidate) (Coordinating Supervisor) "Because you think yourself but one among the many threads which make up the texture of the doublet. You should aim at being like men in general, just as your thread has no ambition either to be anything distinguished compared with the other threads. But I desire to be the purple, that small and shining part which makes the rest seem fair and beautiful. Why then do you bid me become even as the multitude? Then were I no longer the purple." EPICTETUS Acknowledgements First and foremost I would like to thank Dr. George Koutsantonis and A/Prof. Jack Harrowfield for doing the onerous job of being PhD supervisors so well, their discussions about chemistry and pretty much everything else and for their belief in the importance of a strong morning coffee to kick start the day and 4pm beers on Friday to cap off a week of work. The journey that is any PhD would not be the same without the people you share the lab (and solvent roster) with, so I would like to thank the PhD students I have worked with in the lab over the many years, Paul Donnelly, Chris Griffith, Gareth Nealon, Brad Berven, Nicole Hondow, Phil Schauer and Becky Fuller for making the lab an enjoyable place to work and helping keep me sane. Also to the many honours students over the years Dave Dennis, Gareth Jenkins, Alison Steer, Barbara Szepaniack and Tim Allen, cheers. There are of course many people outside the research group that I must thank for their help along the way, in particular, Ylenia Casadio for enduring the trials and tribulations of setting up GPC equipment from scratch with me, Nathan Webster for his help with XRD, weekly laksa lunches and for joining the engineer-turned-chemist pile, and Pete Melloncelli for being the go-to-guy for all my ‘organic’ chemistry woes and sharing my taste in German beer. I must also thank all the non-chemistry students in the MCS building I have got to know, you have given me the opportunity to talk about something besides chemistry at tea breaks, the chance to cross the chemistry/biochemistry ‘invisible’ line and meet some wonderful people, thanks heaps!, particularly to the 4 pm trash talk crew. My visit to Université Louis Pasteur was one of the most enjoyable parts of my PhD, so I am indebted to the hospitality of Prof. Jean-Pierre Sauvage for allowing me to work in his research group. I would like to thank all the people I worked with, became friends with and helped me deal with the French bureaucracy, particularly Dr. Jean-Paul Collin, Julien Frey, Boniet Champin, Yves Rogister, Sana Amir, and all the other chemistry crew in ICOM and Institut Le Bel for showing me a great time and attempting to convince me and everyone else that “Aussies love Fosters mate!”, even if it was brewed in France. I must also acknowledge the financial assistance of a UWA Convocation Alexander Cohen Postgraduate Travel Award and the UWA Postgraduate Travel Award for making the trip possible. Without the superb efforts and hard work of Dr. Brian Skelton and Prof. Allan White the X-ray crystallography presented in this work and resultant ‘pretty pictures’ may never have seen the light of day, thus to both of them I am deeply grateful. I am extremely grateful for all the help I have received from technical staff in the School. Dr. Lindsay Byrne for his seemingly limitless patience and knowledge of NMR, Dr. Tony Reeder for acquisition of Mass Spectra, Oscar Del Borello for assistance with AAS, the ‘workshop boys’, Nigel Hamilton, Andrew Sawyer and Norm Poulter for their help with troublesome equipment and assistance in construction of a spectroelectrochemical cell, and finally Greg Cole and Sarah Davis for their glass blowing expertise. Finally I would like to thanks my friends and family for their support, particularly over the last few months while writing this thesis, I am sure they will be as glad as I am to see it finished. Abstract Abstract Chapter 1 provides an introduction to the ‘sarcophagine’ class of ligands and the field of metallopolymers. The synthesis, stereochemistry, physical properties and functionalisation of ‘sarcophagines’ and their metal complexes are discussed. A brief overview of the burgeoning field of metallopolymers is given with specific mention of the synthetic routes to pendant metallopolymers, and how these could be employed to prepared cage amine containing metallopolymers. Chapter 2 deals with the synthesis, characterisation and reactivity of cinnamylamino and styrylamido derivatives of the cage amines [Co((NH ) sar)]3+, 2 2 [Co((CH )(NH )sar)]3+ and [Cu((NH ) sar)]2+. The cinnamylamino derivatives were 3 2 2 2 prepared using reductive alkylation of the aforementioned amines with cinnamaldehyde. Procedures were developed to isolate the complexes without causing unwanted additions to the double bond. The cinnamylamino derivatives displayed unexpected reactivity towards a range of reducing agents, resulting in unexpected reduction of the double bond and cleavage of the cinnamyl group, but ultimately in the preparation of phenylpropylamino derivatives of [Co((NH ) sar)]3+ and [Co((CH )(NH )sar)]3+. 2 2 3 2 Attempts to rationalise the reactivity of the double bond have been explored based upon the physical properties and reactivity of the double bond. The styrylamido derivatives were prepared by treatment of the cage amines with 4-vinylbenzoyl chloride, and the complexes isolated in a similar manner to those of the cinnamylamino derivatives to ensure the amide linkage remained intact. Most of the complexes have been structurally characterised. Electrochemical examinations of the complexes served not only as a method of characterisation for the complexes, but a possible route to the electropolymerisation of the complexes, unfortunately electropolymerisation was not observed even under a range of conditions. Chapter 3 examines the chemical homopolymerisation and copolymerisation (with styrene) of the cinnamylamino and styrylamide cage amine complexes prepared in chapter 2. Homopolymerisation was not apparent under a range of conditions, but copolymers of both classes of monomers were prepared. The controlled radical polymerisation techniques, RAFT and ATRP, were employed in an attempt to prepare block copolymers of styrene with the cinnamylamino and styrylamide complexes. The i Abstract reactivity of cage amines towards two functionalised polymers, Merrifield resin and poly(vinylbenzoic acid) was explored. Reaction of (NH ) sar with the former gave 2 2 polymers that were capable of coordinating a range of metals. Chapter 4 deals with the synthesis, characterisation and attempted polymerisation of cage amines containing thienyl substituents. Both the 2-thienyl and 3-thienyl derivatives of [Co((NH ) sar)]3+ and [Co((CH )(NH )sar)]3+ have been prepared using reductive 2 2 3 2 alkylation with the respective carboxaldehydes of thiophene. One of the optically pure isomers has been prepared. The complexes have been fully characterised including structural characterisation. Polymerisation of the thiophene-cage amine complexes was investigated under a range of chemical and electrochemical conditions, though polymerisation was never observed. Cleavage of the thienyl groups was observed when ceric ammonium nitrate in nitric acid was used as the oxidant. The attachment of oligothiophenes and mixed pyrrole-thiophene oligomers to cage amines were investigated using reductive alkylation and various pyrrole ring-forming reactions about the apical amino groups, though none of the desired complexes were isolated, reasons for the lack of reactivity were discussed. An efficient synthesis of N-(4-benzoic acid)- 2,5-di(2-thienyl)pyrrole was developed and was shown to the electropolymerisable, albeit the polymer films were non-conducting. Attempts to couple N-(4-benzoic acid)- 2,5-di(2-thienyl)pyrrole with a cage amine via its acid chloride were complicated by decomposition reactions, the nature of one of these products is discussed. Chapter 5 presents investigations into the preparation of simple complexes containing multiple cage amines using alkylation and acylation procedures with aromatic substrates. The complexes were found to exhibit some interesting electrochemical and chemical properties, demonstrating that even simple multiple cage amine species can display complicated and interesting behaviour. ii Abbreviations Abbreviations GENERAL °C Degrees Celsius AAS Atomic Absorption Spectroscopy ABCPA 4,4’-Azobis(4-cyanopentanoic acid) AIBN 4,4’-Azobis(isobutyronitrile) ATRP Atom Transfer Radical Polymerisation BINAP 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl CAN Ceric Ammonium Nitrate conc concentrated CRP Controlled Radical Polymerisation CPDTB 4-Cyanopentanoic acid dithiobenzoate dba Dibenzylideneacetone DBU 1,8-Diazabycyclo[5.4.0]undec-7-ene DeI H O Deionised water 2 DMF Dimethylformamide DMSO Dimethyl Sulphoxide dppf 1,1'-Bis(diphenylphosphino)ferrocene EtOAc Ethyl Acetate, CH CH OC(O)CH 3 2 3 FRP Free Radical Polymerisation IR Infra-red (Spectroscopy) meq/g milli equivalents per gram mmHg Millimetres of Mercury NBS N-Bromosuccinimide (NH ) sar 1,8-Diaminosarcophagine 2 2 (NH )(CH )sar 1-Amino-8-methylsarcophagine 2 3 NMR Nuclear Magnetic Resonance (Spectroscopy) PEDTB 1-Phenethyldithiobenzoate Ph Phenyl (C H -) 6 5 PTSA Para-toluene sulphonic acid (4-methylbenzene sulphonic acid) RAFT Reversible Addition-Fragmentation chain Transfer (polymerisation) rcd recovered R.T. Room Temperature sar Sarcophagine, 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane sen 1,1,1-Tris(1’-amino-3’-azabutyl)ethane SNS Dithienylpyrrole (2,5-di(2’-thienyl)pyrrole) tart Tartrate, C H O 2- 4 4 6 THF Tetrahydrofuran Tol Toluene TRIS Tris(hydroxymethyl)aminomethane (2-Amino-2- (hydroxymethyl)propane-1,3-diol) XRD X-Ray Diffraction (Powder) FOR NUCLEAR MAGNETIC RESONANCE cm complex multiplet COSY Correlation Spectroscopy d doublet dd doublet of doublets m multiplet t triplet HMBC Heteronuclear Multiple Bond Coupling HSQC Heteronuclear Single Quantum Coherence NOE Nuclear Overhausser Effect iii Abbreviations FOR ION EXCHANGE CHROMOATOGRAPHY CM Carboxymethyl (Sephadex) SE Sulphonylethyl (Sephadex) SP Sulphonylpropyl (Sephadex) FOR ELECTROCHEMISTRY ΔE Peak separation in Cyclic Voltammetry ( = E – E ) Red ox CV Cyclic Voltammetry (Cyclic Voltammogram) DPV Differential Pulse Voltammetry E Electrode Potential E Electrode Potential of an Oxidation Process Ox E Electrode Potential of a Reduction Process Red I/I Ratio of anodic and cathodic peak currents a c SCE Standard Calomel Electrode TBAP Tetrabutylammonium Perchlorate FOR MASS SPECTROMETERY FAB Fast Atom Bombardment ESI-MS Electrospray Ionisation Mass Spectrometry EI Electron Ionisation HR High Resolution NOBA 4-Nitrobenzyl Alcohol FOR GEL PERMEATION / SIZE EXCLUSION CHROMATOGRAPHY DAD Diode Array Detector (part of GPC equipment) GPC Gel Permeation Chromatography M Number Average Molecular Weight n M Weight Average Molecular Weight w MW Molecular weight PDI Polydispersity (= M /M ) w n RID Refractive Index Detector (part of GPC equipment) SEC Size Exclusion Chromatography iv