Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Studies of supramolecular chemistry through Schiff-base chemistry Jiang, Jian 2010

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
24-ubc_2010_fall_jiang_jian.pdf [ 15.24MB ]
Metadata
JSON: 24-1.0060358.json
JSON-LD: 24-1.0060358-ld.json
RDF/XML (Pretty): 24-1.0060358-rdf.xml
RDF/JSON: 24-1.0060358-rdf.json
Turtle: 24-1.0060358-turtle.txt
N-Triples: 24-1.0060358-rdf-ntriples.txt
Original Record: 24-1.0060358-source.json
Full Text
24-1.0060358-fulltext.txt
Citation
24-1.0060358.ris

Full Text

    STUDIES OF SUPRAMOLECULAR CHEMISTRY THROUGH SCHIFF-BASE CHEMISTRY  by  Jian Jiang   B.Sc. Jilin University, 1994 M.Sc. Institute of Chemistry, Chinese Academy of Science, 2001   A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF  DOCTOR OF PHILOSOPHY  in  The Faculty of Graduate Studies  (Chemistry)    THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)   August 2010  © Jian Jiang, 2010   Abstract   This thesis describes the synthesis, characterization, and host-guest studies of a series of Schiff-base macrocycles. New [2+2] Schiff-base macrocycles were prepared by Schiff-base condensation. These macrocycles were shown to be wide-mouthed supramolecular hosts that can include organic cations such as pyridinium, paraquat and ammonium derivatives. A new kind of donor-acceptor-donor 3-in-1 complex was obtained in solution by combining macrocycle, cyclobis(paraquat-p-phenylene) and tetrathiafulvalene. Variations of these [2+2] Schiff-base macrocycles were prepared by modifying the substituents of the diformyl diol unit. In this way naphthalene-based macrocycles that undergo keto-enamine tautomerization were synthesized. These macrocycles can also combine with organic cations to form host-guest complex. The naphthalene-based [2+2] macrocycles can form lyotropic liquid crystals in chloroform and 1,2-dichloroethane. From the polarizing optical microscopy, it is proposed that the mesophases are lyotropic nematic liquid crystals based on a bilayer structure. A further study of these macrocycles shows that the host-guest complex can also form a lyotropic liquid crystalline phase. Covalently-linked macrocycles with isosceles triangle shapes were prepared by Schiff- base condensation. The molecular isosceles triangles proved to also be supramolecular hosts for pyridinium and ammonium cations, based on 1H NMR, 2D-ROESY NMR, and mass spectrometry studies. In addition to the Schiff-base macrocycles, conjugated Schiff-base containing oligomers were synthesized via Gilch polymerization methods. The oligomers were characterized by gel permeation chromatography (GPC), thermogravimetric analysis (TGA) and UV-Vis  ii spectroscopy. For further proof of the oligomeric structure, a model compound was prepared by the Wittig reaction.  iii  Table of Contents   Abstract.........................................................................................................................................ii  Table of Contents.........................................................................................................................iv  List of Tables ..............................................................................................................................vii  List of Figures........................................................................................................................... viii  List of Schemes .........................................................................................................................xiv  List of Symbols and Abbreviations ...........................................................................................xvi  Acknowledgements ...................................................................................................................xxi  Co-Authorship Statement .........................................................................................................xxii  CHAPTER 1     Introduction ........................................................................................................1  1.1     Supramolecular Chemistry .................................................................................................1             1.1.1     Defining Supramolecular Chemistry ...................................................................1             1.1.2     Classification of Supramolecular Chemistry Areas.............................................3 1.2     Host-Guest Chemistry ........................................................................................................7             1.2.1     Crown Ethers .......................................................................................................7             1.2.2     Calixarenes ..........................................................................................................9             1.2.3     Cucurbit[n]urils .................................................................................................12             1.2.4     Cyclodextrins.....................................................................................................14             1.2.5     Tetracationic Cyclophanes.................................................................................16 1.3     Rotaxanes..........................................................................................................................18             1.3.1     Synthesis of Rotaxanes ......................................................................................19 1.4     Schiff-base Chemistry ......................................................................................................21             1.4.1     Salen and Salphen..............................................................................................21             1.4.2     Schiff-base Macrocycles....................................................................................24 1.5     Liquid Crystals .................................................................................................................29             1.5.1     Classification of Liquid Crystals .......................................................................30 1.6     Characterization and Techniques......................................................................................34             1.6.1     Characterization of host-Guest Complex with NMR Spectroscopy..................34                           1.6.1.1     Calculation of Association Constants by NMR Titration.................36                           1.6.1.2     Job Plot (Continuous Variation Method)..........................................39                           1.6.1.3     Characterization of Host-Guest Complex with NOESY and ROESY NMR Spectroscopy......................................................41             1.6.2    Characterization of Liquid Crystal by Polarizing Optical Microscopy (POM).............................................................................................44   iv  1.7     Conclusions ......................................................................................................................45 1.8     Goals and Scope of This Thesis .......................................................................................46 1.9     References.........................................................................................................................48  CHAPTER  2     Host-Guest Chemistry of [2+2] Schiff-Base Macrocycles..............................55  2.1     Introduction ......................................................................................................................55 2.2     Discussion.........................................................................................................................56             2.2.1     Synthesis and Characterization of Macrocycles 35 ...........................................56                           2.2.1.1     Assignment of 1H NMR Peaks of Macrocycle 35 ............................62                           2.2.1.2     Simulations of Macrocycle 35 ..........................................................65             2.2.2     Synthesis and Characterization of Macrocycles 38 and 43 ...............................67             2.2.3     Host-Guest chemistry of Schiff-base Macrocycles ...........................................72                           2.2.3.1     Complexes Formed by Macrocycles and Their Guests ....................72                           2.2.3.2     Formation of Host-Guest-Guest 3 in 1 Complex..............................83 2.3     Conclusion ........................................................................................................................93 2.4     Experimental.....................................................................................................................93 2.4.1     General...............................................................................................................93 2.4.2     Synthesis and Characterization..........................................................................94 2.5     References.......................................................................................................................102   CHAPTER 3     Covalently-Linked Molecular Isosceles Triangles.........................................108  3.1     Introduction ....................................................................................................................108 3.2     Discussion.......................................................................................................................109             3.2.1     Synthesis and Characterization of Isosceles Triangle 58 ................................109             3.2.2     Synthesis and Characterization of Macrocycle 59...........................................116             3.2.3     Host-Guest Chemistry of Macrocycles 58 and 59 ...........................................120 3.3     Conclusions ....................................................................................................................126 3.4     Experimental...................................................................................................................126 3.4.1     General.............................................................................................................126 3.4.2     Synthesis and Characterization........................................................................127 3.5     References.......................................................................................................................132  CHAPTER 4     Naphthalene-based Keto-Enol Tautomerized [2+2] Macrocycle...................134  4.1     Introduction ....................................................................................................................134 4.2     Discussion.......................................................................................................................135             4.2.1     Synthesis and Characterization of 66 and 67...................................................135             4.2.2     Liquid Crystal Formed by Macrocycles and Complexes ................................142                           4.2.2.1     Liquid Crystal Formed by Macrocycle 67......................................142                           4.2.2.2     Liquid Crystal Formed by Host-Guest Complex............................150 4.3     Conclusions ....................................................................................................................155 4.4     Experimental...................................................................................................................156             4.4.1     General.............................................................................................................156             4.4.2     Synthesis and Characterization........................................................................156             4.4.3     Characterazation by Polarizing Optical Microscopy.......................................159  v 4.5     References.......................................................................................................................161  CHAPTER 5     Synthesis and Characterization of a Conjugated Metal-Containing Poly(P-Phenylenevinylene) Analogue............................................................163  5.1     Introduction ....................................................................................................................163 5.2     Discussion.......................................................................................................................166 5.3     Conclusions ....................................................................................................................177 5.4     Experimental...................................................................................................................177             5.4.1     General.............................................................................................................177             5.4.2     Synthesis and Characterization........................................................................178 5.5     References.......................................................................................................................183  CHAPTER 6     Conclusions And Future Directions ...............................................................187  6.1     Overview ........................................................................................................................187 6.2     [2+2] Schiff-base Macrocycles.......................................................................................188 6.3     Molecular Isosceles Triangles ........................................................................................192 6.4     Naphthalene-based [2+2] Schiff-base Macrocycles .......................................................193 6.5     References.......................................................................................................................195  APPENDICES ..........................................................................................................................196  Appendix A  Job Plots (continuous variation methods) ...........................................................196  A1     Experiment procedure for Job plots................................................................................196 A2     Job Plots..........................................................................................................................196  Appendix B  Titration curves and stacked 1H NMR spectra ....................................................200  B1     Experiment procedure for NMR titrations ......................................................................200 B2     Titration curves and stacked 1H NMR spectra................................................................200          vi  List of Tables   Table    2.1     Binding constant (Kassoc) of the complexes formed by association of macrocycles and guests at 300 K in CDCl3 (The concentration of hosts was kept constant at 1.28×10-3 M during titration.)...........................................................................80  Table    3.1     Kinetic parameters for the macrocycle 58 and 59. ...........................................119  Table    3.2     Binding constant (Kassoc) of the complexes formed by association of macrocycles and guests at 300 K in CDCl3..........................................................................124  Table    4.1     Binding constant (Kassoc) of the complexes formed by association of macrocycles and guests at 300 K in CDCl3..........................................................................141  Table    5.1     Summary of polymerization attempts to obtain polymer 82. ...........................171                    vii  List of Figures   Figure 1.1.  Complexes formed between melamine and imides. (1, 1:1 complex; 2, 1:2 complex; 3, 1:3 complex.). .....................................................................................................2  Figure 1.2.  Illustration of molecular recognition (lock and key model). (The red cross means that no reaction happens.).. ......................................................................................4  Figure 1.3.  Structure of supramolecules. (4 rotaxane, 5 catenane, 6 foldamer and 7 molecular cage)..........................................................................................................................5  Figure 1.4.  Templation of a hexadecamer from guanine and potassium ions and linkage of the olefins with Grubbs’ catalyst. (Used with the permissionof American Chemical Society, copyright 2006.).............................................................................6  Figure 1.5.  Conformations of calix[4]arene (a cone, b partial cone, c 1,3-lternate, d 1,2-alternate)............................................................................................................................10  Figure 1.6.  Lower rim functionalized calixarene hosts.. ..........................................................11  Figure 1.7.  Dimerization of urea-substituted calix[4]arene. (Used with the permission of The National Academy of Sciences, copyright 1995.). .......................................11  Figure 1.8.  (a) Side view of dimer containing an encapsulated benzene guest. (b) Top view of dimer containing chloroform. (Used with the permission of The National Academy of Sciences, copyright 1995.) . ....................................................................12  Figure 1.9.  Structure of CB[5] CB[10]. (Used with the permission of Wiley InterScience, copyright 2002.)....................................................................................................13 ⊂  Figure 1.10.  Structure of cyclodextrins.. ..................................................................................14  Figure 1.11.  The formation of cyclodextrin supramolecular polymer. (Used with the permission of American Chemical Society, copyright 2005.)..............................................15  Figure 1.12.  Crystal structure of TTF CBPQT⊂ 4+. (Used with the permission. .....................17  Figure 1.13.  The structures of some tetracationic cyclophanes................................................18  Figure 1.14.  Rotaxane and three strategies of synthesis.. .........................................................20  Figure 1.15.  (a) Photograph of gel in methol under light (left) and when irradiated with UV light (right). (b) Fiber morphology of Zn-salphen observed by TEM. (used with the permission of Wiley InterScience, copyright 2007).................................24  Figure 1.16.  Space-filling model of ion-induced tubular assembly of macrocycle 27 with Na+.. ...............................................................................................................................27  viii  Figure 1.17.  Typical examples (and molecular shapes) of the main types of molecules forming LC phases. (Adapted from ref. 63b). ...........................................................31  Figure 1.18.  Presentation of the main types of nematic and positional ordered thermotropic LC phases formed by rod-like and disk-like molecules. (Adapted from ref. 63b)..............................................................................................................................32  Figure 1.19.  Presentation of the main types of lyotropic LC phases. (Adapted from 63b). ...................................................................................................................................33  Figure 1.20.  (a) The illustration of micelles in Nd phase. (b) The illustration of micelles in Nc phase....................................................................................................................34  Figure 1.21.  Setup of a polaried optical microscope.. ..............................................................45 Figure 1.22.  The [2+2] Schiff-base macrocycles......................................................................47 Figure 2.1.  Structure of Schiff-base macrocycles.....................................................................57  Figure 2.2.  1H NMR spectrum (300 MHz, CDCl3) of 39. ........................................................59  Figure 2.3.  Comparison of the 1H NMR spectra of 39 before and after deuteration (400MHz, 298K, CDCl3:MeOD = 20:1).. ...............................................................60  Figure 2.4.  1H NMR Spectrum of macrocycle 35 (400 MHz, 298K, CDCl3). .........................62  Figure 2.5.  1H NMR Spectrum of the macrocycle 35 between 6.5-7.1 ppm............................63  Figure 2.6.  (a) 2D-ROESY spectrum of macrocycle 35 with a mixing time of 120 ms (400 MHz, CDCl3, 298K). (b) Enlarged spectrum from 2.8 ppm to 4.5 ppm (F1) and from 5.5 ppm to 7.4 ppm (F2). ............................................................................65  Figure 2.7.  Representative energy-minimized conformations of macrocycle 35 as deduced by semi-empirical (PM3) measurements.  The energy of the conformation is shown beneath each structure. (Nomenclature from calixarene chemistry.) ..................................................................................................................................66  Figure 2.8.  1H NMR spectrum of macrocycle 41 (400 MHz, CDCl3, 298K)...........................68  Figure 2.9.  Representative energy-minimized conformations of macrocycle 41 as deduced by semi-empirical (PM3) measurements. The energy of the conformation is shown beneath each structure. ................................................................................................69  Figure 2.10.  1H NMR spectrum of macrocycle 46 (400MHz, CDCl3, 298K)..........................71  Figure 2.11.  1H NMR spectra of (a) cetylpyridinium chloride (48+·Cl-); (b) mixture of macrocycle 35 and cetylpyridinium chloride ([CPC]:[1] = 5:1); and (c)  ix macrocycle 35 (400 MHz, CDCl3, 298 K). The peaks are assigned as shown in the molecular structures above the spectra. ......................................................................................73  Figure 2.12.  2D-ROESY spectrum of the host-guest complex formed by macrocycle 35 and cetylpyridinium chloride 48+·Cl- with a mixing time of 120 ms (400 MHz, CDCl3, 298 K)..........................................................................................................75  Figure 2.13.  Energy-minimized (PM3) model of 48+⊂35 complex space- filling view from bottom; (b,c) side views. (The alkoxy chains of the macrocycle were removed for calculation and the alkyl chain of the pyridinium was  truncated to ethyl.) ..........................................................................................................................................76 spectrum of polymer 202a in THF (λexc = 406 nm).  Figure 2.14.  2D-ROESY spectrum of complex formed by macrocycle 41 and cetylpyridinium chloride 48+Cl- with a mixing time of 120 ms (400 MHz, CDCl3, 298K). .........................................................................................................................................77  Figure 2.15.  MALDI-TOF mass spectrum of host-guest complex 48+⊂ 35. ..........................78  Figure 2.16.  Job plots of (a) 48+⊂  35 and (b) 48+⊂ 41 (400 MHz, CDCl3, 298 K). ...............................................................................................................................................78  Figure 2.17.  Molecules investigated as potential guests for macrocycles 35 and 41. ...............................................................................................................................................79  Figure 2.18.  (a) The 1H NMR spectra (3:1 CDCl3/CD3OD) of macrocycle 35 before and after addition of 562+ (0 – 2.5 equiv). (b) Enlarged region from 5.8 – 6.4 ppm of the titration spectra. (400 MHz, 298K; [35] = 8.63×10-3 M) ...................................82  Figure 2.19.  Job plot of macrocycle 35 with guest 562+ in CDCl3/CD3OD (3:1) (400 MHz, 298 K). ....................................................................................................................83  Figure 2.20.  The illustration of 2:1 complex (a) and 1:1 complex (b) formed by macrocycle 35 and 562+. .............................................................................................................83  Figure 2.21.  Partial of 2D-ROESY spectrum of the complex formed by macrocycle 43 and CBPQT4+ in 1:1 CDCl3/CD3CN with a mixing time of 120 ms (400 MHz, 298K). Structures are shown beside the spectrum to show proton assignments.................................................................................................................................85  Figure 2.22.  The assignment of spin-couplings and the corresponding conformations. (The guest in structure (a) rotates 90º to give (b) and the guest in (c) rotates 90º to give (d). The alkoxy chains are omitted for clarity.) The structures shown are models that account for the observed ROESY spectrum, not calculated conformations. ...........................................................................................................86  Figure 2.23.  Job plot of macrocycle 46 with CBPQT4+ in 1:1 CDCl3/CD3CN (400 MHz, 298 K). .....................................................................................................................87   x Figure 2.24.  (a) Partial of 1H NMR spectra of different combinations of macrocycle 46, CBPQT4+ and TTF (400 MHz, acetone-d6, 298K). (b) Enlarged spectral region around 6.6 ppm from (a). ...................................................................................88  Figure 2.25.  Partial of 2D-ROESY spectrum of the complex formed by macrocycle 46, CBPQT4+, and TTF in 1:3 CDCl3/CD3CN with a mixing time of 400 ms (400 MHz, 298K). Labelled structures above the spectrum show proton assignments. (The peaks near 7.2 ppm are attributed to the aromatic protons on ketimine phenyl rings. As these peaks were not resolved, “ar” to denote them collectively.) ...............................................................................................................................90  Figure 2.26.  MALDI-TOF mass spectrum of the host-guest-guest complex. .........................91  Figure 2.27.  Energy minimized (MMFF) models of the host-guest-guest complex formed between macrocycle 46, CBPQT4+, and TTF. (a) and (b) show the top and side views of one conformation; (c) and (d) show the top and side views of another. Alkoxy chains and hydrogen atoms are removed for clarity. ........................92  Figure 3.1.  Structure of molecular isoscelestriangles 58 and 59. ..........................................109  Figure 3.2.  Energy minimized (PM3) structure of 58 (a) top space-filling view; (b,c) side views. (The alkoxy chains of the macrocycle are not shown as they were not included in the calculation.).......................................................................................111  Figure 3.3.  1H NMR spectrum of macrocycle 58 (400 MHz, CDCl3, 298K). .......................112  Figure 3.4.  (a) Partial of 2D-ROESY spectrum of macrocycle 58 from 12.5 to 15.3 ppm (F1) and from 12.5 to 15.3 ppm (F2) (b) Partial of 2D- ROESY spectrum of macrocycle 58 from 13.4 to 13.8 ppm (F1) and from 8.5 to 8.7 ppm (F2) (c) Partial of 2D-ROESY spectrum of macrocycle 58 form 5.7 to 6.6 ppm (F1) and from 3.2 to 4.4 ppm (F2). (The peak assignment of these ROESY spectra is based on the structure in Figure 3.3; All three graphics are from the same 2D- ROESY spectrum, but with different intensity scaling.) (400 MHz, CDCl3, 298K)................113  Figure 3.5.  Partial of 2D 1H-1H COSY NMR spectrum of 58 from 3.5 ppm to 4.2 ppm for F1 and from 3.5 ppm to 4.3 ppm for F2 (400MHz, CDCl3, 298K). (c) The structure that leads to diastereotopic protons Hg1 and Hg2. ...............................................115  Figure 3.6.  Representative energy-minimized conformations of macrocycle 58 as deduced by semi-empirical (PM3) calculations. The energy of the conformation is shown beneath each structure. ..................................................................................................115  Figure 3.7.  (a) 1H NMR spectrum of macrocycle 59 (400 MHz, CDCl3, 298 K). (b) 2D 1H-1H COSY NMR spectrum of macrocycle 59 (400 MHz,  CDCl3, 298 K). .............................................................................................................................................118  Figure 3.8.  Partial 1H VT-NMR spectrum of macrocycle 59 (From 3.4 to 4.4 ppm) (400 MHz, 1,1,2,2-tetrachloroethane-d2). .......................................................................119   xi Figure 3.9.  (a) (i) Partial 1H NMR spectrum of macrocycle 58 from 5.0 to 15.0 ppm. (400 MHz, CD2Cl2, 298 K) (ii) Partial 1H NMR spectrum of mixture of cetylpyridinium chloride 48+Cl- and macrocycle 58 (400 MHz, CD2Cl2, 298 K, [48+]:[58] = 3:1) (iii) 1H NMR spectrum of pyridinium chloride 48+Cl- (400 MHz, CD2Cl2, 298 K). (b) (i) 1H NMR spectrum of macrocycle 58 (400 MHz, CDCl3, 298 K) (ii) 1H NMR spectrum of mixture of cetylpyridinium chloride 48+Cl- and macrocycle 59 (400 MHz, CDCl3, 298 K, [48+]:[59] = 5:1) (iii) 1H NMR spectrum of pyridinium chloride 48+Cl- (400 MHz, CDCl3, 298 K)........................................120  Figure 3.10.  2D-ROESY NMR spectrum of the complex formed by macrocycle 58 and cetylpyridinium chloride 48+Cl- with a mixing time of 120 ms (400 MHz, CD2Cl2, 298 K). ........................................................................................................................122  Figure 3.11.  Computer model of the complex with one of conformations of macrocycle 58 and the assignment of spin-spin coupling from 2D- ROESY. (a) guest orientate “up” (b) guest orientate “down”.......................................................................123  Figure 3.12.  (a) MALDI-TOF mass spectrum of complex 48+⊂ 58 (dithranol as matrix). (b) Job Plot of macrocycle 58 with cetylpyridinium chloride 48+·Cl- in CDCl3 (400 MHz, CDCl3, 298 K). ...........................................................................................124  Figure 4.1.  Structures of macrocycles 30, 59, 66 and 67. ......................................................134  Figure 4.2.  (a) 1H NMR spectrum of macrocycle 66. (400MHz, CDCl3, 320K). (b) 2D 1H-1H COSY spectrum of macrocycle 66 ( 400MHz, CDCl3, 298K). ...............................137  Figure 4.3.  Partial 1H NMR spectra of (a) macrocycle 66; (b) mixture of macrocycle 66 and cetylpyridinium chloride 48+·Cl- ([48+]:[66] =1.2:1); and (c) Cetylpyridinium chloride (400 MHz, CDCl3, 298 K). The peaks are assigned as shown in the molecular structures. ...........................................................................................138  Figure 4.4.  (a) 2D-ROESY NMR spectrum of complex formed by macrocycle 66 and cetylpyridinium chloride with a mixing time of 120 ms (400 MHz, CDCl3, 298 K). The circled cross-peaks (Ha and Hc; Hb and Hd) are couplings between macrocycle 66 and cetylpyridinium 48+. ..................................................................................139  Figure 4.5.  (a) The proposed preferred conformation of the host-guest complex 48+⊂ 66. (b) The illustration of the complex 48+⊂ 66. ............................................................140  Figure 4.6.  Molecules investigated as potential guests for macrocycles 35 and 66. ............................................................................................................................................141  Figure 4.7.  Structures of some macrocycles that can give lyotropic mesophases. ................143  Figure 4.8.  (a) Polarized optical micrographs (50×) of 10 wt % 62 / 90 wt % chloroform at room temperature. (b) A closer view of texture.................................................143  Figure 4.9.  Polarized optical micrographs (50×) of 20 wt% 67 / 80 wt% chloroform at room temperature...............................................................................................145  xii  Figure 4.10.  Proposed preferred conformation of 67 after CMC. (Simulated by empirical calculation (PM3))....................................................................................................146  Figure 4. 11.  Structure of macrocycle 72. ..............................................................................147  Figure 4.12.  Proposed bilayer structure by macrocycle 67. ...................................................147  Figure 4.13.  (a) Polarized optical micrographs (50×) of 5 wt% 67 / 95 wt% 1,2- dichloroethane at room temperature. (b) Polarized optical micrographs (50×) of macrocycle 67 in a mixture of 1,2-dichloroethane / chloroform (1:3) at room temperature. ..............................................................................................................................149  Figure 4.14.  Polarized optical micrographs (50×) of phase transition between Nd and focal conic domain.............................................................................................................150  Figure 4.15.  Optical photomicrographs obtained for the mesophase of inclusion complex 84+⊂61 (a) Polarized optical micrographs (20×). (b) Polarized optical micrographs (50×). ..................................................................................................................151  Figure 4.16.  Optical photomicrograph of crystals of cetylpyridinium chloride. ...................152  Figure 4.17.  Optical photomicrographs obtained with crossed polars for the mesophase of inclusion complex 48+⊂ 61 in 1,1,2,2-tetrachloroethane. .................................154  Figure 5.1.  Structure of monomer 75. ....................................................................................166  Figure 5.2.  (a) GPC result of polymer 82. (b) Thermogravimetric analysis of polymer 82. ...............................................................................................................................173  Figure 5.3.  (a) NMR Spectra of polymer 82 (400 MHz, CD2Cl2, 298K). (b) IR spectrum of polymer 82 and monomer 75 (around 1500 cm-1). ...............................................174  Figure 5.4.  UV-vis spectra (1.0 cm cell, 298K, CH2Cl2) of monomer 75, polymer 82, and model compound 83.....................................................................................................176            xiii  List of Schemes   Scheme 1.1.  Redox-switching [2] catenane. ...............................................................................2  Scheme 1.2.  The original reaction to form a crown ether.. .........................................................8  Scheme 1.3. The formation of molecules with multiple crown ethers and poly[2]pseudorotaxane (Adapted from ref. 20).. ..........................................................................9  Scheme 1.4.  Synthesis of cucurbit[6]uril. ................................................................................13  Scheme 1.5.  Synthesis of CBPQT4+..........................................................................................16  Scheme 1.6.  Synthesis of the first rotaxane. .............................................................................19  Scheme 1.7.  Synthesis of a rotaxane by the clipping approach. ...............................................21  Scheme 1.8.  General Schiff-base condensation reactions between a carbonyl compound and a primary amine. ................................................................................................22  Scheme 1.9.  Formation of salen and salphen. ...........................................................................23  Scheme 1.10.  The epoxidation of indene using Jacobsen’s catalyst.........................................23  Scheme 1.11.  Synthesis of Robson-type macrocycles. .............................................................26  Scheme 1.12.  Synthesis of [3+3] Schiff-base macrocycle. .......................................................26  Scheme 1.13.  Synthesis of tautomerized Schiff-base macrocycle. ..........................................28  Scheme 1.14.  Synthesis of [6+6] Schiff-base macrocycle 33. ..................................................29  Scheme 1.15.  Spin state and transition probabilities for a two spin system. ............................42  Scheme 1.16.  The NOESY pulse sequence. .............................................................................44  Scheme 2.1.  Synthesis of precursor 36. ...................................................................................58  Scheme 2.2.  Synthesis of precursor 39 .....................................................................................58  Scheme 2.3.  Synthesis of macrocycle 35. .................................................................................61  Scheme 2.4.  Synthesis of macrocycle 41. .................................................................................67  Scheme 2.5.  Preparation of precursor 42. .................................................................................70  Scheme 2.6.  Synthesis of macrocycle 46. .................................................................................71  xiv  Scheme 3.1.  Synthesis of molecular isosceles triangle 58. .....................................................110  Scheme 3.2.  Synthesis of macrocycle 59. ...............................................................................116  Scheme 4.1.  Synthesis of macrocycle 66 and 67. ...................................................................136  Scheme 4.2.  Proposed scheme of the formation of Nd and lamellar phase.............................148  Scheme 4.3.  Formation of columnar phase by an inclusion complex.....................................151  Scheme 4.4.  Model for assembly of amphiphilic molecules to form micelles. (a) Amphiliphilic molecules with a disc-like shape aggregate to rod-like micelles. (b) Amphiphiles with a rod-like shape aggregate to disc-like micelles. ........................................153  Scheme 4.5.  Proposed model for the formation of Nc phase by host-guest complex. ...................................................................................................................................154  Scheme 5.1.  Postulated mechanism for Gilch polymerization route to PPV 74. ....................165  Scheme 5.2.  Synthesis of compound 80..................................................................................167  Scheme 5.3.  Synthesis of monomer 75. ..................................................................................168  Scheme 5.4.  Synthesis of polymer 82. ....................................................................................169  Scheme 5.5.  The formation of quinodimethane-like intermediate..........................................172  Scheme 5.6.  Synthesis of model compound 83.......................................................................176  Scheme 6.1.  Reaction of 39 and 25 in room temperature without catalyst.............................189  Scheme 6.2.  Synthesis of [2+2] macrocycle by templation methods. ....................................190  Scheme 6.3.  Synthesis of a [2]catenane. .................................................................................191  Scheme 6.4.  Synthesis of a [3]catenane. .................................................................................192  Scheme 6.5.  Proposed synthesis of metallated macrocycles with two different metals........................................................................................................................................193         xv  List of Symbols and Abbreviations  Abbreviation   Description  Å    Ångstrom ⊂     is included in δ    chemical shift Δ    reflux, change λ    wavelength λmax    wavelength at bond maximum ε    molar absorptivity/molar extinction coefficient (M-1cm-1) a.m.u    atomic mass units Bu    butyl tBu    tertiary-butyl C    complex Calc’d     calculated CB    cucurbituril CBPQT   cyclobis(paraquat-p-phenylene) CD    cyclodextrin Cin     cinnamoyl CIS     complexation induced shift cmc    critical micelle concentration Col    columnar phase  xvi COSY    correlation spectroscopy CPC    cetylpyridinium chloride CT     charge transfer d     doublet DCE    1,2-dichloroethane DCM     dichloromethane DDQ     2,3-dichloro-5,6-dicyanobenzoquinone DMF     Dimethylformamide DFT    Density functional theory DMSO    Dimethyl sulfoxide E    energy eq    equation, equivalent ESI    electrospray ionization FCD    focal conic domain G    guest GPC    gal permeation chromatography H    host HRMS    high resolution mass spectrometry I    intensity i.e.    id est (that is to say) IR     Infrared K     Kelvin, equilibrium constant Kassoc     association constant LC     liquid crystal LEDs    light emission diodes  xvii LLC    lyotropic liquid crystal M    molarity (molL-1) m     multiplet MALDI    matrix-assistted laser desorption ionization Me     methyl group MMFF    molecular mechanics force field mmol     millimoles Mn    number-average molecular weight mol     moles M.P.    melting point MS    mass spectrometry m/z    mass-to-charge ratio NBS     N-bromosuccinimide Nc    calamitic nematic phase Nd    discotic nematic phase NMR     nuclear magnetic resonance p    para Ph     phenyl PM3    Parameterized Model number 3 POM    polarizing optical microscopy PPV     poly(p-phenylene vinylene) R.B. flask    round-bottom flask ROE    Rotating Frame Overhause Effect ROESY   Rotating Frame Overhause Effect Spectroscopy R.T.    room temperature  xviii s    singlet salen    N,N’-bis(salicylidene)ethylenediamine salphen   N,N’-bis(salicylidene)phenylenediamine Sm    smectic phase SmA    smectic A phase SmC     smectic C phase T    temperature tBu     tertiary-butyl TEM     transmission electron microscopy TGA     Thermogravimetric Analysis THF    tetrahydrofuran TOF    time of flight TTF     tetrathiafulvalene UBC    University of British Columbia υ    frequency UV    ultraviolet Vis     visible VPO    vapor pressure osmometry VT    variable temperature μL    microliter μM    micromolar wt    weight X    halogen   xix  Acknowledgements  I would like to thank my charming supervisor Prof. Mark MacLachlan for his excellent guidance throughout this work. Mark is an exceptional teacher and a great friend, and his wisdom and optimism made this challenging project possible. Thanks also to the MacLachlan group members who have helped me throughout this work, in and out of the lab. A special thanks to Dr. Alfred Leung who helped familiarize me with organic synthesis and for training on many instruments when I first joined this lab. Many thanks to Prof. Derek Gates who nicely gave me opportunities to access his GPC. I am grateful for the many helpful talks and discussions with Z. Paul Xia (NMR) and Yun Ling (mass spectrometry) from whom I have learned so much. I would like to thank the UBC Chemistry Department staff and personnel who have helped me to have a good time at UBC. I would like to thank my family and friends who have helped me and encouraged me during my study at UBC.            xx  Co-authorship Statement  A portion of chapter 2 has been published as a communication to the editor: Frischmann, P. D.; Jiang, J.; Hui, J. K.-H.; Grzybowski, J. J.; MacLachlan, M. J. “Reversible-irreversible approach to Schiff base macrocycles: access to isomeric macrocycles with multiple salphen pockets.” Org. Lett. 2008, 10, 1255. I am the second author and one of the principal investigators of this work under the supervision of Prof. Mark MacLachlan. I synthesized compounds 11a, 12 and 13. Frischmann synthesized compound 10 and studied the kinetic properties of ketimines and aldimines. Hui synthesized compounds 11b and 14. Prof. Grzybowski, a visiting professor in our lab, was the first person who worked on this project. He synthesized compound 7 in this paper. A portion of chapter 2 has been published as a communication to the editor: Jiang, J; MacLachlan M. J. “Cationic guest inclusion in widemouthed Schiff base macrocycles.” Chem. Commun. 2009, 5695. I am the primary author and carried out all of the experiments for this work under the supervision of Prof. Mark MacLachlan. I wrote the first draft of the manuscript and participated in editing of the paper with Prof. MacLachlan. A version of chapter 3 has been published as a communication to the editor: Jiang, J; MacLachlan M. J. “Unsymmetrical triangular Schiff base Macrocycles with cone conformations.” Org. Lett. 2010, 12, 1020. I am the primary author and carried out all of the experiments for this work under the supervision of Prof. Mark MacLachlan. I wrote the first draft of the manuscript and participated in editing of the paper with Prof. MacLachlan. A version of chapter 4 will be submitted for publication: Jiang, J; MacLachlan M. J. “Lyotropic Liquid Crystal Formed by naphthalene-based Schiff-base Macrocycle”. I am the  xxi primary author and carried out all of the experiments for this work under the supervision of Prof. Mark MacLachlan. I wrote the first draft of the manuscript and participated in editing of the paper with Prof. MacLachlan. A version of chapter 5 was recently published: Jiang, J.; Leung, A. C. W.; MacLachlan, M. J. “Synthesis and Characterization of an Oligomeric Conjugated Metal-Containing Poly(p- phenylenevinylene) Analogue” Dalton. Trans. 2010, 39, 6503. I am the primary author and conducted most of the experiments for this work under the supervision of Prof. Mark MacLachlan. Leung helped me to synthesize some of the compounds in this paper and measure the molecular weight of the oligomer with GPC. I wrote the first draft of the manuscript and participated in editing of the paper with Prof. MacLachlan.    xxii Chapter 1 Introduction 1.1 Supramolecular Chemistry 1.1.1 Defining Supramolecular Chemistry  “Supramolecular chemistry” was defined by Jean-Marie Lehn, who shared the Nobel prize in 1987 for his contribution in this field, as “chemistry beyond the molecule.” Lehn explained this definition as “supramolecular chemistry is the chemistry of the intermolecular bond, covering the structures and functions of the entities formed by association of two or more chemical species.”1 Unlike molecular chemistry, which has established control over the covalent bond, supramolecular chemistry focuses on the weak and reversible noncovalent interactions between molecules.2 These weak intermolecular forces include electrostatic effects, hydrogen bonding, metal coordination, Van der Waals forces, and π-π interactions. The goal of supramolecular chemistry is to construct new molecules and materials with function by controlling the intermolecular weak bonds. For example, by changing the shape of components, melamine and imides can form supramolecular 1:1, 1:2, and 1:3 complexes (structures 1-3 in Figure 1) via hydrogen bonding.3   1 N N NN N N N N H O O C3H7 H H HH H H N N O O HC3H7 N N OO H C3H7 NN N NN N NO O H H H HH H H N N N N N N H H H H H H N N N N N N H H H H H H N O O H N O O H N O O H N O O H 1:1                         1:2                                 1:31                 2                         3 1 2 3  Figure 1.1 Complexes formed between melamine and imides (1, 1:1 complex; 2, 1:2 complex; 3, 1:3 complex.).  As the structures show in Figure 1.1, supramolecular species are organized structures composed of two or more chemical units held together by weak forces. Supramolecular structures are not simply the additive results of individual components, but can instead be well-defined functional architectures whose properties are different than the sum of the properties of each subunit.4 An example of a supramolecular structure behaving as a cooperative system is the redox-switching [2]catenane synthesized by Stoddart et al. (Scheme 1.1)5  Scheme 1.1 Redox-switching [2] catenane. N N N N O O O OO O S S S S O OO O N N N N S S S S O OO O O O O O O O - e- + e-   2  Because tetrathiafulvalene (TTF) is a better electron donor than 1,5-dioxynaphthalene, in the above catenane, the most stable isomer is that in which the TTF unit occupies the cavity of the electron-accepting cyclobis(paraquat-p-phenylene) (CBPQT4+). However, with the addition of Fe(ClO4)3 to the system, TTF is oxidized to TTF+·, which results in repulsion between the CBPQT4+ and the TTF+· radical cation and, thus, the inclusion of the 1,5-dioxynaphthalene moiety into the cyclophane. Supramolecular assembly is common in biology and much of the early inspiration came from biological assembly: lipid bilayers, viral capsids, the DNA duplex, and the tertiary and quaternary structure of proteins.6 Supramolecular chemistry is interesting both for its biological relevance, and because it is a new approach to complex structures having nanometer to millimeter dimensions that are difficult or impossible to prepare by traditional techniques.7 In this chapter, I introduce the field of supramolecular chemistry, emphasizing concepts relevant to the rest of the thesis. I also describe Schiff base chemistry and macrocycles as they are the basis of my work. Finally, I describe less common techniques and methods I have applied in my research.  1.1.2  Classification of Supramolecular Chemistry Areas  Although supramolecular chemistry is still a young field, it has developed rapidly. Nowadays, people study supramolecular chemistry mainly in three directions: (a) molecular recognition chemistry; (b) building specific shapes/architectures; and (c) molecular assembly organized from numerous molecules. Molecular recognition is fundamental to supramolecular chemistry. Molecular recognition can be regarded as the “lock and key” model, a notion first enunciated by Emil Fisher in 1894,8  3 implying geometrical and electrostatic complementarities between two or more components (Figure 1.2).  host molecule guest molecule guest molecule complex   Figure 1.2 Illustration of molecular recognition (lock and key model) (The red cross means that no reaction happens.).  In its simplest sense, molecular recognition can be regarded as selective binding or complexing. The process can be, generally, considered as one molecule (host) binding another molecule (guest) to produce a host-guest complex. The host is often a larger molecule such as a macrocycle or molecular capsule and the guest can be a monatomic cation, an organic cation, an inorganic anion, or even a neutral molecule. Either the host or the guest, or both, have binding sites that are capable of taking part in non-covalent interactions with the other. Using host-guest chemistry, some molecules can be self-assembled to give medium-sized supramolecular structures that can have very impressive shapes and interesting properties. For example, one can assemble a “rotaxane”, a molecule composed of a macrocycle and an end-capped thread molecule that is threaded through the cavity of macrocycle. In this molecule, two separate molecules (the thread and the macrocycle) are bound to each other by non-covalent  4 interactions. Catenanes consist of two or more interlocked macrocycles that cannot be separated without breaking the covalent bonds of the macrocycles. Foldamers are discrete molecules or oligomers that adopt a secondary structure stabilized by non-covalent interactions. Molecular cages are composed of one or more molecules that are assembled by covalent or non-covalent bonds to form a 3D cage-like structure. Small guest molecules can be bound inside the cage via intermolecular weak forces. Examples of these supramolecular structures are illustrated in Figure 1.3.  Figure 1.3 Structure of supramolecules (4 rotaxane, 9  5 catenane, 10  6 foldamer 11  and 7 molecular cage12).  Non-covalent interactions play a leading role in controlling the secondary and tertiary structures of natural macromolecules such as polypeptides and polynucleotides. In recent years, intermolecular interactions, such as hydrogen bonding, π-π stacking and metal coordination, N NN N N OO O N O O OO O O O N O O O O O O O O O N O NN O O O N N O O O O O RR OO 4                                               5 4 5 R R NN N N 6                                        7 N O RR H OO O N O N H R' N O N R' H O NH N H N HR' O O N R' N H H R' NHR' R' O R N H H O N H NH R'NH N H O O O R OO RR  5 have been exploited in the molecular self-assembly of synthetic highly directional polymeric architectures.13 The advantage of preparing macromolecules via self-assembly is minimizing structural defects in the product by preventing the undesired subunits from incorporating into the architectures during assembly. The structural integrity of final product is preserved due to the recognition through non-covalent interactions. For example, because of the high-fidelity and directionality during DNA duplication, assembly via hydrogen-bonding between base-pairs, the basis for the structure of DNA double helix, has attracted much attention in recent years. Many examples of well-defined highly ordered assemblies as well as polymeric systems have been made from analogues of nucleobases. An example of self-assembly via base-pair complementarity is the hexadecamer of guanine (Figure 1.4).14 Guanine assembles into a cyclic tetramer (G-quartet) in the presence of alkali metals, such as Na+ or K+. In addition to the stabilizing hydrogen bonding, guanine possesses an aromatic surface that is polarizable and contains a strong molecular dipole. The hydrogen bond and polar aromatic surfaces facilitate the stacking of tetramers into hexadecamers. The hexadecamer can be further stabilized via the use of metathesis polymerization to link the olefins and tether the subunits into fixed positions.15 O O O O O O O N N NH N O NH2 = Grubb’s CatalystK+  Figure 1.4 Templation of a hexadecamer from guanine and potassium ions and linkage of the olefins with Grubbs’ catalyst (Taken from reference 15. Used with the permission of American Chemical Society, copyright 2006.).  6  1.2  Host-Guest Chemistry  In 1967, Pedersen reported that alkali metal ions bind crown ethers to form highly structured complexes.16 This discovery gave fundamentally new concepts to chemistry in general and prompted the generation of a new field---supramolecular chemistry. In the following decades, many kinds of novel macrocyclic hosts were synthesized or discovered, including cryptands, calixarenes, resorcinarenes, cucurbiturils, cyclodextrins and cyclophanes. 17  In host-guest chemistry, a host molecule may selectively recognize its guest through many kinds of non-covalent interactions, such as electrostatic attraction, hydrogen bonding, metal coordination, Van der Waals forces and π-π stacking. Host-guest chemistry was recognized as a fundamental aspect of molecular recognition and self-assembly. Many smart artificial systems have been designed by using principles of host-guest chemistry. An enormous potential lies in future applications of host-guest chemistry in the field of nanotechnology, catalysis, environmental protection and medicine.  1.2.1 Crown Ethers  Crown ethers were the first artificial macrocyclic hosts discovered. Macrocyclic polyethers were actually first synthesized in 1930s18 but little study followed so that their ability to complex small cations was not recognized. When Pedersen tried to synthesize bisphenol, a small amount of by-product of cyclic hexaether was obtained (Scheme 1.2). This cyclic compound substantially increased the solubility of potassium permanganate in benzene or chloroform.    7 Scheme 1.2 The original reaction to form a crown ether. OH O O + Cl O Cl O O O O O O 0.4%   Based on this observation, Pedersen suggested that a complex structure was formed and the metal ion was trapped inside the cavity of the crown ether. Since then, a series of crown ethers were synthesized and many of them are commercial available, such as 15-Crown-5, 18-Crown-6 and 21-Crown-7. Crown ethers and structural analogues have attracted significant attention from various fields of science.19 In recent years, considerable studies have been devoted to the design of multiple crown ether derivatives, which can be used in multicomponent host-guest interaction or in the construction of higher-order complexes. For example, a dibenzo[24]crown-8-containing di-Pt(II) acceptor building block was self-assembled into a series of different sized and shaped multiple crown ether derivatives when it combined with dipyridyl donors. Based on this multiple crown ether scaffold, poly[2]pseudorotaxanes formed when secondary alkylammonium ions were added into the system, as shown in Scheme 1.3.20          8  Scheme 1.3 The formation of molecules with multiple crown ethers and poly[2]pseudorotaxane (Adapted from ref. 20). +3 3 = O O O O OO O O O O PtPt PEt3 TfO Et3P OTf PEt3 Et3P = N N = N HH   1.2.2 Calixarenes  Calixarenes are macrocycles or cyclic oligomers based on a hydroxyalkylation product of a phenol and an aldehyde.21 The term generally describes cyclic arrays of n phenol moieties linked by methylene groups even though the larger systems do not form calyx (vase) shaped structures. Calixarene nomenclature is straightforward and involves counting the number of repeating units in the ring and include it in the name (e.g., calix[4]arene). Calixarenes are usually depicted with their phenolic groups down (lower rim) and their para-substituents pointing upward (upper rim). Calixarenes with free hydroxyl groups are conformationally flexible and the molecule can adopt different extreme conformations. For example, from the low-temperature H NMR spectrum of calix[4]arene in solution, it consists of a mixture four conformations: cone, partial cone, 1  9 1,3-alternate and 1,2-alternate, as shown in Figure 1.5.22 Both the upper and lower rims of calixarenes can be functionalized and the properties of these vase-like hosts can be altered.  OHOH HOOH OH OH OH OH OHOH OHOH OH OH OH OH a b c d Figure 1.5 Conformations of calix[4]arene (a cone, b partial cone, c 1,3-alternate, d 1,2-alternate).  The first ionophores designed to bind alkali metals based on calixarenes were obtained by adding ester or ketone functionalities to the lower rim of calixarene 8 (shown in Figure 1.6).23 The hard cations, such as Li+, Na+, K+, Rb+ and Cs+, bind strongly to the hard donating carbonyl atoms and four ethereal oxygen atoms on 8. The stability constants of the alkali-metal complexes are in the range of 102-106 M-1.24 However, the selectivity of binding of alkali ions with these ligands is not good. Calix[4]arene crown ethers 9 have been designed and synthesized for selective complexation of alkali metal ions.25 When the size of the ethyleneoxy-bridged ring increases, calix[4]arene crown ethers 9 favours binding to larger alkali metal ions. Compound 10 was synthesized by substitution of the carbonyl functionalities or ether chain with phosphine oxide ligands at lower rim. Compound 10 prefers to selectively complex di- and trivalent cations, such as Ca2+, Eu3+ and Pu3+.26   10 8  R= OAlkyl or Alkyl 9 n= 1,2,3 10   R’= P(O)(Ar)2 OO OO RO O OR O R OO EtOOEt O O n OO OO R' R' R'R' R  Figure 1.6 Lower rim functionalized calixarene hosts.  In addition to the modification on the lower rim of calixarene to bind cations, calixarenes with four urea substituents on their upper rims can dimerize into a molecular capsule via hydrogen bonding (Figure 1.7).  Figure 1.7 Dimerization of urea-substituted calix[4]arene (Taken from reference 12. Used with the permission of The National Academy of Sciences, copyright 1995.).  The dimeric capsule is held together by a cyclic array of intermolecular C=O…H-N hydrogen bonds. Four of the urea moieties, which contain C=O and H-N groups, come from the top hemisphere and four come from the bottom. Urea-substituted monomers exhibit C4  11 symmetric cone-conformations and the dimers have S8 symmetry due to the directionality of the cyclic array. The cavity inside the capsule can reversibly encapsulate smaller molecules such as chloroform, benzene, and toluene, as shown in Figure 1.8.  Figure 1.8 (a) Side view of dimer containing an encapsulated benzene guest. (b) Top view of dimer containing chloroform (Taken from reference 12. Used with the permission of The National Academy of Sciences, copyright 1995.).  1.2.3 Cucurbit[n]urils  Although the synthesis of cucurbit[6]urils (CB[6]) was reported more than 100 years ago,27 it was not until 1981 that their structures and chemical properties were fully characterized by Mock.28 By condensation of glycoluril and formaldehyde, Mock obtained the cyclic hexameric macrocycle that contains 24 C-N bonds and six eight-membered rings with complete control over the relative orientation of glycoluril C-H atoms, which point out of the cavity, as shown in Scheme 1.4. Subsequent work showed that CB[6] exhibits very strong and selective binding toward organic cations29 and metal ions30 in water. The discoveries of CB[5], CB[7] and CB[8] by Kim and co-workers expanded the CB[n] family and provided hosts with a wide range of available cavity sizes.31 Due to the superior solubility of CB[n] in aqueous solution, numerous  12 investigations into host-guest behaviour of CB[n] were performed, especially the encapsulation of bioactive molecules.32  Scheme 1.4 Synthesis of cucurbit[6]uril. N N N N O N NN N N N N N O O O N N N N O O N N N N O N N N N O O O O O O H H H HNHHN NHHN O O HH CH2O HCl H2O  An interesting supramolecular structure in which a smaller macrocycle, CB[5], is located inside a larger macrocycle, CB[10], ( CB[5] CB[10])was reported by Day and coworkers,⊂ 33 as shown in Figure 1.9. The crystal structure of this complex shows an angle of 64º was formed between the axis of CB[5] and the axis of CB[10]. In addition, there is a chloride ion included at the centre of CB[5]. NMR studies indicated that, in solution, CB[5] and CB[10] are freely rotating relative to each other. The association constant for CB[5] CB[10] in a solution of 18% w/v DCl/D ⊂ 2O is > 106.  Figure 1.9 Structure of CB[5] CB[10] (Taken from reference 33. Used with the permission of Wiley InterScience, copyright 2002.). ⊂  13  1.2.4 Cyclodextrins  Cyclodextrins were first isolated in 1891 by Villiers,34 but the correct chemical structures of cyclodextrins were not determined until 1938.35 Cyclodextrins are obtained in large scale by enzymatic degradation of starch. Mainly three cyclodextrins are available, α-, β-, and γ- cyclodextrin consisting of six, seven and eight D-glucose units, respectively, attached by α-1,4-linkages (Figure 1.10). O OH HO OHO OOH OH OH O O OH OH HO OO O OH OH HO O OH HO HO O O OHHO OH O O OH HO OH O O OH HO OHO OOH OH OH O O OH OH OH OO OH OH HO O O OH OH HO O O OH HO HO O O OH HO OH O O OH HO OHO OOH OH OH O O OH OH OH O O OH OH HO O OH OH HO O O OH HO HO O O OH OH HO O O  α-cyclodextrin             β-cyclodextrin             γ-cyclodextrin Figure 1.10 Structure of cyclodextrins.  Cyclodextrins have macrocylic hollow cone structures composed of the chiral glucose units in rigid 4C1-chair conformations. The primary hydroxyls of the glucose units are located at the narrow side of the cone and the secondary hydroxyls at the wide side. Because of the primary and secondary hydroxyls on cyclodextrins, the macrocycles are very soluble in water. Due to relatively apolar cavity and polar exterior, cyclodextrins can form inclusion complexes with a large range of hydrophobic guests in aqueous solutions predominantly driven by hydrophobic interactions.36 Cyclodextrins are now one of the most important molecular hosts for research because they  14 are semi-natural products. A review paper indicated that there are thousands of papers published on cyclodextrins relating to supramolecular complexes, pharmaceuticals, environmental protection and foods.37 Constructing supramolecular structures with cyclodextrins has become very attractive in recent years. Through host-guest interactions of cyclodextrins, supramolecular polymers were obtained by Harada and co-workers (Figure 1.11).38 To obtain the supramolecular polymer, a host, α-cyclodextrin, and a cinnamoyl-containing guest were incorporated in a single molecule (Cin-α-CD). To prevent the formation of an intramolecular complex, a rigid cinnamoyl group, which is unable to bend inside the cyclodextrin, was used as the guest.38d = HNCCC HH O  Figure 1.11 The formation of cyclodextrin supramolecular polymer (Take from reference 38e. Used with the permission of The Royal Society of Chemistry, copyright 2009.).  When the cinnamoyl group was attached to the wider side of α-cyclodextrin, the Cin-α-CD then gave a longer polymer even at low concentration. The molecular weight measured from VPO (vapour pressure osmometry) of the supramolecular polymer was about 20000 (20 repeat units).    15  1.2.5 Tetracationic Cyclophanes  Tetracationic cyclophanes are interesting molecules that have been extensively studied over the past two decades. Since cyclobis(paraquat-p-phenylene) (CBPQT4+) 11 was synthesized by Stoddart and co-workers, a variety of rotaxanes, catenanes, and molecular switches were obtained by exploiting the properties of the tetracationic cyclophane. The synthesis of CBPQT4+ was first reported in 198839 via a two-step reaction (Scheme 1.5). Due to its tetracationic nature, CBPQT4+ forms very stable inclusion complexes with electron-rich species, such as tetrathiafulvalene (TTF),40 diphenol methyl ethers,41 dinaphthol methyl ethers42 and amino acids.43 Based on the above discovery of inclusion properties of CBPQT4+, many advances in the development of nanoscale machines have been achieved44 The strong binding property of CBPQT4+ arises from the conformational rigidity of this cyclophane, which has a box-like structure with a very well-defined cavity lined by the two paraquat acceptor units.  Scheme 1.5 Synthesis of CBPQT4+. Br Br + N N N N N N Br Br N N N N 1111 The assembly formed by CBPQT4+ and TTF (TTF CBPQT⊂ 4+) was reported in 1991. The white-coloured CBPQT4+ and brown-coloured TTF combine to give a green-coloured 1:1  16 complex. Single crystal X-ray crystallography of the complex shows that the TTF molecule is inserted through the centre of CBPQT4+ with slight twisting of the bipyridinium units. The structure of the complex is shown in Figure 1.12. NMR chemical shifts and the appearance of a charge-transfer absorption band at 854 nm (which gives the green colour) also proved the formation of the inclusion complex. NMR titration experiments indicate the association constant of the complex is as high as 1×104 M-1.45  Figure 1.12 Crystal structure of TTF CBPQT⊂ 4+ (Taken from reference 40. Used with the permission of the Royal Society of Chemistry, copyright 1991.).  Following the synthesis of CBPQT4+, many kinds of tetracationic cyclophanes were synthesized for different proposes. For example, cyclophane 12 was designed and synthesized to detect the origin of intermolecular factors that control CBPQT4+ binding selectivity and affinity.46 Pyrrole-functionalized cyclophane 13 was prepared to introduce the electro-active pyrrole moiety into CBPQT4+. The [2]rotaxane formed from 13 was deposited onto an electrode surface, and its structure contained a poly(pyrrole) with CBPQT4+ side groups. 47 Carbazolophane 14 was synthesized to investigate the photophysical properties of the 4,4’-bipyridine-based tetracationic cyclophane.48  17 NN N N O N N N N O NO N Et N N N N N Et 12 13 1412 13 14  Figure 1.13 The structures of some tetracationic cyclophanes.  1.3 Rotaxanes  Host-guest chemistry, based on specific molecular recognition, is fundamental to supramolecular chemistry and can also be used to obtain larger assemblies. Supramolecular structures have been attracting much attention due to their interesting geometric features. Among them, mechanically interlocked molecules such as catenanes and rotaxanes have unique shapes and supramolecular topologies. Catenanes are intertwined macrocycles and rotaxanes consist of a molecular ring (macrocycle) trapped on a linear molecular thread by bulky ‘stoppers’ at both ends. The name rotaxane is derived from the Latin for wheel (rota) and axle (axis). The thread is a dumbbell shaped molecule that is retained inside the macrocycle because the ends of dumbbell are larger than the internal cavity of the macrocycle. Rarely do the thread and macrocycle spontaneously form a rotaxane when combined, but instead are assembled using non-covalent interactions, such as electrostatic attraction or hydrogen bonding.  18  1.3.1 Synthesis of Rotaxanes  The synthesis of a rotaxane was first reported in 1967 by I. T. Harrison and S. Harrison as shown in Scheme 1.6.49 This rotaxane was obtained only by statistical probability. If two parts of the thread molecule were connected together in the presence of a macrocycle, a small amount of thread could be trapped inside the macrocycle. This reaction gave a 6% yield after treatment of resin-supported macrocycle with thread for 70 times.  Scheme 1.6 Synthesis of the first rotaxane. ( CH2)28 CH-C OR O + (CH2)8 CH2H2CHO OH + C Cl ( CH2)28 CH-C OR O (CH2)10 OC(C6H5)3OC(C6H5)32   With the development of supramolecular chemistry, rotaxanes were synthesized via self-assembly using molecular recognition instead of statistical probability. There are three methods used to prepare rotaxanes: capping, clipping and slipping methods (Figure 1.14). Synthesis of rotaxanes by capping methods is based on a thermodynamically driven template effect, which involves the threading of a linear molecule though the cavity of a macrocycle by non-covalent bonds, to generate a pseudorotaxane that is then transformed into a rotaxane by reaction with a bulky stopper.   19 Macrocycle Dumbbell shaped molecule Capping: + Clipping: + Slipping   Figure 1.14 Rotaxane and three strategies of synthesis.  Templated-directed synthesis of rotaxane by the clipping approach involves clipping together the macrocycle segments on the thread which has already been stoppered. The first rotaxane synthesized by clipping methods was reported in 1991 by Stoddart and co-workers, as shown in Scheme 1.7.50  This synthesis involved the formation of a Schiff-base macrocycle 15 by condensation of 2,6-pyridinecarboxaldehyde and tetraethyleneglycolbis(2-aminophenyl)ether. When thread 16 was present during Schiff-base condensation, a thermodynamically stable rotaxane 17 was obtained. But because of the kinetic lability of macrocycle 15 due to the hydrolysis of the imine group, rotaxane 17 is not very stable at room temperature and it was difficult to isolate. A kinetically stable rotaxane 18 was obtained by reducing of 17 with borane. Rotaxane 18 is very stable and was isolated in 70% yield.    20  Scheme 1.7 Synthesis of a rotaxane by the clipping approach.  N H OO H + NH2 O O O O O H2N N N N O O O O O N OMe OMe MeO OMe H H PF6- N N N O O O O O N OMe OMe MeO OMe H H BH3 N NH HN O O O O O N OMe OMe MeO OMe H H PF6-PF6 - 15 16 1718  In the slippage approach to rotaxanes, the macrocycle and stopper-attached thread are synthesized separately and mixed together. If the size of stopper is appropriate, a reversible threading process can happen at high temperatures where an energy barrier has to be overcome. By cooling the products, kinetically stable rotaxanes can sometimes be obtained.      21  1.4 Schiff-base Chemistry  1.4.1 Salen and Salphen  Condensation of carbonyl compounds with primary amines to form imines was discovered in 1864 by Hugo Schiff51 and the product is now called a Schiff-base compound. Because of its reversible nature and simple synthetic conditions, Schiff-base condensation (as shown in Scheme 1.8), has found its way into many different areas of chemistry.52  Scheme 1.8 General Schiff-base condensation reactions between a carbonyl compound and a primary amine.  H2N R' C NC O + R H R' H R + H2O H2N R' C NC O + R R'' R' R'' R + H2O ( R'' = - CH3 , - Ph , etc ) ( Aldimine ) ( Ketimine )  N,N’-bis(salicylidene)ethylenediamine (salen) and N,N’-bis(salicylidene)-1,2-diaminobenzene (salphen) are two examples of well-studied Schiff-base compounds within the field of homogeneous catalysis.53 These compounds are made from two carbonyl moieties and one diamine, as shown in Scheme 1.9.    22  Scheme 1.9 Formation of salen and salphen. OH O 2 OH N N HO + 2 H2O H2N NH2 H2N H2N OH N N HO + 2 H2O Salen Salphen With a tetradentate N2O2 pocket, these Schiff-base compounds can bind metal ions to form coordination complexes. Schiff-base complexes have been used as catalysts in many organic reactions including the epoxidation of olefins, lactide polymerization and asymmetric ring opening of epoxides. For example, commercially available Jacobsen’s catalyst 19 is a chiral catalyst and used in asymmetric epoxidation of indene (Scheme 1.10).54  Scheme 1.10 The epoxidation of indene using Jacobsen’s catalyst. NN O O Mn Cl ORRO tBu tBu tBu tBu ONaOCl / H2SO4 19   Salens have been reported recently as a building block for supramolecular assemblies. Some  23 salen-pyridine-based compounds have been reported to self-assemble into loop-type structures.55 Zn-salphens have been discovered by our group to fabricate nanowires and gels via intermolecular interaction of Zn…O between Schiff-base complexes.56  N N O O Zn RO OR R= C6H13, C14H29, C16H33, 2-ethylhexyl   Figure 1.15 (a) Photograph of gel in methanol under light (left) and when irradiated with UV light (right). (b) Fiber morphology of Zn-salphen observed by TEM (Taken from reference 56. Used with the permission of Wiley InterScience, copyright 2007.).  1.4.2 Schiff-base Macrocycles  Reversibility of the Schiff-base condensation reaction makes it ideal for forming rings. During the last two decades, many kinds of methods of fabricating Schiff-base macrocycles  24 starting from various dicarbonyl compounds and diamines were developed toward the synthesis of symmetrical and unsymmetrical macrocycles.57 The reactions of dicarbonyl compounds with diamines are actually very complicated and oligomers or polymers may form, but under the appropriate conditions thermodynamically stable macrocycles can be obtained. Since the report of Robson’s inaugural [2+2] macrocycle, Schiff -base macrocycles have proved useful in the study of metal-ligand interactions.58 These macrocycles, which are easily synthesized by reacting a diamine monomer with a diformyl monomer of an appropriate geometry to yield a single macrocycle, have been the subject of much recent investigation. A series of [2+2], [3+3], [4+4] and [6+6] Schiff-base macrocycles were reported. The shape of the macrocycles depends on the geometry and stoichiometric ratio of the starting materials, as well as other conditions such as solubility of starting material, polarity of solvent, and presence of template. The first Robson-type macrocycle was prepared by reaction of 2,6-diformyl-4-methylphenol 20 with 1,3-diaminopropane 21 in the presence of a metal salt. Synthesis of these macrocycles without a metal template only gave oligomers. However, it was found that by adding acid into the system, metal-free Robson-type macrocycles (e.g., 24) were formed, as shown in Scheme 1.11.59          25  Scheme 1.11 Synthesis of Robson-type macrocycles. OHO O + NH2 NH2 CuCl2 ON N N NO Cu Cu2 2 OHO O + OHNH2 NH2 HCl N N OH HO N OH N HO H H 2 2 20 21 22 20 23 24 Reaction of 2,3-dihydroxyl-1,4-diformylbenzene 25 with 4,5-diamino-1,2-dialkoxylbenzene 26 under catalyst-free conditions gives [3+3] macrocycles 27 (Figure 1.12).60  Scheme 1.12 Synthesis of [3+3] Schiff-base macrocycle. OH OH O O + NH2 NH2 RO RO N N OH OH HO HO N N N N HO OH RO OR OR ORRO RO 20 25 7 26  Conjugated [3+3] Schiff-base macrocycle 27 contains three tetradentate N2O2 binding sites  26 organized in an equilateral triangle, as well as a pocket in the centre that is surrounded by six phenolic oxygen atoms resembling 18-crown-6. Upon adding Na+ into the solution of 27, a color change from orange to red was observed. The NMR spectrum and ESI-MS of the mixture showed that a tubular assembly of macrocycle with Na+ was formed (Figure 1.16).    Figure 1.16 Model of ion-induced tubular assembly of macrocycle 27 with Na+.  The methods of condensing o-phenylendiamines with aromatic 1,4-dialdehydes was successfully applied to naphthalene derivatives. 61  Naphthalene-incorporated Schiff-base macrocycle 29 was shown to tautomerize into the keto-enamine structure of 30 (Scheme 1.13). In a mixture of tautomers, the keto-enamine isomer is the predominant component.          27 Scheme 1.13 Synthesis of tautomerized Schiff-base macrocycle.  OH OH O O + NH2 NH2 RO RO N N OH OH HO HO N N N N HO OH RO OR OR ORRO RO NH HN O O O O NH HN NH HN O O RO OR OR ORRO RO 28 26 29 30  A variety of Schiff-base macrocycles with different shapes can be obtained by utilizing different starting materials. A big [6+6] Schiff-base macrocycle 33 can be obtained when 1,3-diformylresorcinol 31 is used. To synthesize 33, an intermediate compound 32 was first prepared by Schiff-base condensation. Compound 32 reacted with 1 equivalent of 31 to give macrocycle 33, as shown in Scheme 1.14.             28 Scheme 1.14 Synthesis of [6+6] Schiff-base macrocycle 33. HO OH O O + H2N NH2 RO OR HO OH N N NH2 NH2 OR RO OR OR HO OH N N N N OR RO OR OR OH OH HO OHN N N NOH OH OH HO N N N N HO OH RO RO RO OR OR OR OR OR HO OH O O 31 26 32 31 33  1.5 Liquid Crystals  Liquid crystals (LCs) are an interesting type of supramolecular structure as they are held together by non-covalent bonds. They are different than the molecular structures discussed already, but I introduce them because LCs are described in this thesis. LCs are anisotropic fluids with some degree of orientational ordering, but no long range  29 periodicity – they lie between crystalline solids and isotropic liquids on a phase diagram. Because LC mesogens are composed of a rigid segment and flexible alkyl chains (thermotropic LCs) or hydrophobic and hydrophilic parts (lyotropic LCs), these molecules spontaneously aggregate together by micro-phase separation methods to give LC phases. LCs serve as model systems for cell membranes and muscles, and they have found widespread use in displays, sensors and in optical elements such as controllable lenses and in lasing.62 LC science and technology is crossing the boundaries of many fundamental scientific disciplines.  1.5.1 Classification of Liquid Crystals  In LC phases, the order of the crystalline state is partially lost, and the constituent molecules, aggregates, or particles are mobile.63 There are two kinds of LC materials: thermotropic LCs and lytropic LCs. Thermotropic LC phases are obtained by a change of temperature, while lyotropic LC phases are observed in the presence of a suitable solvent (over some concentration range).64 Thermotropic LCs can be further classified by their molecular shape including linear rod-like (calamitic), disc-like and bent (or banana-like) molecules, as shown in Fig. 1.17. The rod-like LCs are the most well known LCs which are widely used in LC displays and other electro-optic devices. The first examples of disc-like molecules forming LC phases were reported in 1977 by Chandrasekhar et al...65 Disc-like LCs are now being investigated for applications in the field of molecular electronics and high-efficiency organic photovoltaics. 66  In 1996, Niori et al. discovered a novel type of LC with a bent core and this kind of LC was called a banana-like liquid crystal.67 Banana-like liquid crystals rapidly became one of the most exciting research areas within the LC area due to the unusual ferroelectric and antiferroelectric responses, the induction of supramolecular chirality and other unique properties.68 There are also other shapes of LCs, such as T-shaped, cone LCs, dendrimer LCs and rod-coil polymer LCs.69  30 NN O O O O O N N R R OCnH2n+1 OCnH2n+1 H2n+1CnO H2n+1CnO OCnH2n+1 OCnH2n+1 N Br- Anisometric e.g.   Figure 1.17 Typical examples (and molecular shapes) of the main types of molecules forming LC phases (Adapted from ref. 63b).  The nematic phase is the least ordered LC phase, and molecules that compose nematic LC possess orientational ordering and no positional ordering. For nematic LC molecules, the rigid core leads to a parallel organization of these units and the flexible chains provide some degree of mobility to prevent crystallization. Both rod-like and disc-like (as well as bent-core) LC molecules can form nematic phases. Molecules in other LC phases, such as smectic (Sm) and columnar (Col) phases, also exhibit some positional ordering. Smectic phases, with layer ordering, are usually observed for the elongated rod-like molecules. There are two most important smectic phases: the smectic-A phase (SmA), in which the long molecular axes of the molecules are perpendicular to the layer planes, and the smectic-C phase (SmC), in which the molecules are tilted by an angle with respect to the layer normal, as shown in Figure 1.18.70.  31 Nu ND NCol SmA SmC Colh Colob Colr z z n Nematic Smectic Columnar   Figure 1.18 Presentation of the main types of nematic and positional ordered thermotropic LC phases formed by rod-like and disc-like molecules (Adapted from ref. 63b).  The formation of thermotropic LCs is driven by the segregation of rigid aromatic cores from flexible alkyl tails within a molecule. LC phase formation in lyotropic LCs is driven by the segregation of hydrophobic and hydrophilic regions of an amphiphilic molecule. The typical types of lyotropic LC phases formed by amphiphilic molecules are shown in Figure 1.19. Depending on the concentration, as well as the shapes of molecules, temperature, and pressure, different LC phases can be formed. Typical lyotropic systems, based on the packing symmetry of the ordered domains, include the lamellar phase, bicontinuous cubic phases, hexagonal columnar phases, and micellar cubic phases. Water is the most commonly used solvent for lyotropic liquid crystal. Starting from pure water, addition of amphiphile leads to formation of micelles above a  32 certain concentration, named the critical micelle concentration (cmc). With increasing amphiphile to water ratio, the phases formed are micellar cubic (CubI), hexagonal columnar (Colh) and cubic (CubV). At a certain ratio, curved interfaces are no longer formed and lamellar phases result. A continued increase in the amphiphile-to-water ratio will result in the formation of inverted phases, i.e., the formation of inverse bicontinuous cubic, columnar and micellar cubic phases.71  Hydrophilic head group Hydrophobic tail(s) micelle Reversemicelle Molar ratio (Water). Xwater 10 cmc LamellarColh Colh CubICubI CubV e.g.: e.g.: CubV curvature 0 Normal phasesInverted phases  Fig. 1.19 Presentation of the main types of lyotropic LC phases (Adapted from 63b).  Besides the lyotropic mesophases shown in Figure 1.19, lyotropic nematic phases have been known since 1976. 72  Unlike the thermotropic nematic phase, which was composed of directionally ordered small molecules, the lyotropic nematic liquid crystal consisted of oriented micelles. The micelles are of bilayer structure composed of amphiphilic molecules. Two kinds of  33 lyotropic nematic phases were extensively studied: calamitic nematic phase (Nc) and discotic nematic phase (Nd). Nc and Nd are consisted of bilayer micelles, but the orientation of the micelles are different in magnetic field, as shown in Figure 1.20. Both Nc and Nd phase exhibit schlieren textures. The difference between Schlieren textures of Nc and Nd have been summarized in previous studies.73 n n (a) (b)  Figure 1.20. (a) The illustration of micelles in Nd phase. (b) The illustration of micelles in Nc phase.  1.6 Characterization and Techniques  1.6.1 Characterization of Host-Guest Complexes with NMR Spectroscopy  The development of supramolecular chemistry has required the development of many new techniques, such as mass spectrometry methods and NMR methods. Characterizing the large supramolecular structures often held together by weak interactions requires the application of many techniques. In this thesis, a variety of instrumental methods were employed. Among these, some less common methods used to study host-guest complexes were used, and these are  34 discussed in this section. The most direct way to characterize the formation of a host-guest complex is by single crystal X-ray diffraction. Many host-guest complexes have been characterized by this method,74 but it has many limitations. To perform X-ray crystallography, it is necessary to obtain single crystals, which is very difficult for many systems. Also, it does not give any information about the solution structure. Other methods, such as NMR spectroscopy, UV-Vis spectroscopy, and mass spectrometry are extensively used to characterize inclusion complexes. The characterization of a host-guest complex by UV-Vis is usually based on charge transfer between host and guest responsible for the intense colours characteristic of many complexes. The charge-transfer bands, or CT bands, frequently occur in the visible region of the electromagnetic spectrum. Mass spectrometric analysis of supramolecular structures has been advanced by the invention of soft ionisation techniques such as electrospray ionization (ESI)75  and matrix assisted laser desorption ionization (MALDI), 76  and the development of high resolution instruments. With ESI and MALDI mass spectrometry, relatively weak non-covalent complexes formed in solution or present in the solid-state can be transferred to gas phase as intact complexes and their intrinsic properties can be studied without the interference of solvent. Properties such as stoichiometry of formed complexes, relative binding affinities,77 and stability of the complexes78 can be obtained from MS analysis. Although experimental techniques such as UV-Vis and mass spectrometry are becoming more powerful analytical methods for the characterization of supramolecular complexes, the most informative and widely used analytical method employed for the study of species in solution is nuclear magnetic resonance (NMR) spectroscopy. By evaluating simple parameters, such as chemical shifts and spin-spin couplings, component interactions, association constants and conformational changes can be elucidated easily. Newer methods that enable measurement  35 of diffusion constants and through-space interactions have made NMR extremely powerful.  1.6.1.1 Calculation of Association Constants by NMR Titration.  Binding of a guest to a host induces changes in chemical shifts. These changes are termed complexation induced shifts (CIS) and can give a significant amount of information about the functional group interaction and aromatic ring current effects of host-guest complex in solution. Association constants of host-guest complex can be calculated from complexation induced shifts.79 For a reaction that forms a 1:1 complex: H + G C k1 k-1 ( H = host, G = guest, C = complex)  H and G may be in fast or slow exchange with the complex C on the 1H NMR time-scale.80 For both fast and slow exchange, the formal (i.e., initial) concentrations of host and guest can be expressed as: [H0] = [H] + [C] = nh [H0] + nc [H0]          (1) [G0] = [G] + [C] = ng [G0] + nc [G0]          (2) ( nh, ng and nc are the mole fraction of host, guest and complex, respectively)  The association constant can be expressed as: 0 [ ] [ ] [ ][ ] [ ]([ ] [ ]) C CK H G H G C = = −     (3)  36 0 0 [ ] ([ ] [ ])([ ] [ ]) CK H C G C = − −     (4) cnK = 0[ ] (1 )( )c c H n R n− −                (5) Where R is the ratio [G0]/[H0]  In a complex undergoing slow (or no) exchange, there are different chemical shifts observed for a specific proton of H and C, and also G and C. The association constant K can be calculated from the signal integrals (I). If Ih denotes the integral of a signal for one specific proton of H (host) and Ic the integral for the same proton in the C (complex), the concentration of C at equilibrium is  0[ ] [ ]c h c IC I I = + H                (6)  Substituting eq (6) into eq (4), then yields eq (7) for the association constant K. 0 0[ ] [ ] c c h h c IK II G H I I = ⎡ −⎢ ⎥+⎣ ⎦ ⎤              (7) By contrast, under fast-exchange conditions there is just one signal for the specific proton on H and G at the population-averaged chemical shift.  h h c cn nδ δ= + δ                 (8)  Based on this relationship, δ  can be expressed as  (1 ) ( ) ( )c h c c h c c h h cn n n nδ δ δ δ δ δ δ= − + = + − = − Δδ      (9)  37  From Equation 5, we find 2 0 (1 )( ) ( 1) ( ) [ ] c c c c n n R n R R n n K H = − − = − + + c or 2 0 1( ) 1 0 [ ] cn R n R K H ⎡ ⎤− + + + =⎢ ⎥⎣ ⎦ c           (10)  The real root of this quadratic equation is given by  2 4 2 c b b Rn − −=                (11) where 0 11 [ ] b R K H = + +  Substituting Equation 11 into Equation 9 gives Equation 12:  ( )2 42h b b Rδδ δ Δ⎛ ⎞= − − −⎜ ⎟⎝ ⎠            (12) where 0 11 [ ] b R K H = + + In Equation 12, δ  is the chemical shift of a specific proton for host and guest, which can be directly obtained from the NMR titration. hδ  is the chemical shift of the proton on the host molecule. Then δΔ  and K can be calculated by nonlinear curve-fitting based on the NMR titration data.  38  In a typical experiment, the host macrocycle is dissolved in an appropriate amount of deuterated solvent in a vial. A measured quantity of this is transferred to an NMR tube. The guest compound is dissolved in the host solution in the vial to form a host-guest solution. By microsyringe, the host-guest solution was added, in calculated amount, into the NMR tube containing the host solution. Binding constants are calculated by nonlinear curve fitting methods for the guest-induced chemical shifts of selected peaks. This method is useful for determining the association constant of 1:1 host-guest complexes. If the stoichiometry of the complex is not 1:1 (e.g., 1:2 or 3:1), much more complicated equations arise. Fortunately, there is some free software available to calculate association constants of complexes that are not 1:1, such as EQNMR.81  1.6.1.2 Job Plot (Continuous Variation Method)  In host-guest chemistry, it is important to know the stoichiometry of the complex – whether one or more guests are binding to a host. The stoichiometry of the complex can be determined by the method called a “Job plot”.82 In this method, the sum of the concentration of host and guest are held constant, but their mole fractions are varied. The arithmetic product of chemical shift and mole fraction is plotted against the mole fraction of the two components. The maximum on the plot corresponds to the stoichiometry of the two species. In the equilibrium equation H + nG C The total concentration [T] of H and G is kept constant while the ratio r = [H]/[T] is varied. The chemical shift change of H is measured and the concentrations can be written as:  [H] = [H0] – [C]                  (13)  39 [G] = [G0] – n[C]                  (14) [H0] = r [T]                   (15) [G0] = [T] – r [T]                  (16)  From Equation 8  h h c cn nδ δ= + δ c                  (8)  we can find  (1 )c h c c h c h cn n n nδ δ δ δ δ= − + = − + δ ( )h c c hnδ δ δ− = −δ h c c h n δ δδ δ −= −                  (17) [ ] [ ] c C T δ δ Δ= Δ [ ] [ ] c C Tδδ Δ= Δ                  (18)  Substituting Equation15, Equation 16 and Equation 18 into Equation 4 gives  [ ] 1 [ ] [ ][ ] [ ] [ ]c c c r TK r T nr Tr T T r T δ δ δδ δ δ Δ= ΔΔ ⎡ ⎤ ⎡− − −⎢ ⎥ ⎢Δ Δ⎣ ⎦ ⎣ Δ ⎤⎥⎦      (20)   40 When r δΔ  is plotted against , a parabola is obtained with maximum at r 1r = ( 1)n + Then, n = 1:  maximum at  = 1/2    (1:1 complex) r n = 2:  maximum at  = 1/3    (1:2 complex) r  To perform an experiment, host and guest compounds are dissolved in deuterated solvent in NMR tubes, keeping the total concentration of host and guest constant. Normally, the molar fraction of host and guest in the resulting solution in NMR tubes vary from 0.1 to 0.9. The changes in chemical shifts (Δδ) are multiplied by molar fraction and plotted against molar fraction to obtain the Job plot.  1.6.1.3 Characterization of Host-Guest Complex with NOESY and ROESY NMR Spectroscopy  Although 1D NMR techniques, such as NMR titrations and Job plots, have played important roles for characterization of host-guest complexes, it is difficult to obtain useful information that establishes the structures or conformations of complexes from 1D NMR spectra. The invention of 2D NMR spectroscopy, such as COSY and NOESY, made up for the weaknesses of the 1D NMR technique. 2D NMR spectroscopy provides more information about molecules than 1D NMR experiments. Nuclear Overhauser Effect Spectroscopy (NOESY) is one of the most important 2D NMR techniques because it correlates pairs of nuclei in the molecule (or complex) that are close together in space (distance smaller than 5 Å). The position of cross peaks and peak intensity in a NOESY spectrum can provide information about the spatial proximity and conformation of complexes. The 2D NOESY technique relies on the Nuclear Overhauser Effect83 which was first  41 observed in 1953. When two nuclei located in a magnetic field B1 are close together in space, dipole-dipole relaxation occurs between these two nuclei. Irradiating one of these nuclei with another magnetic field B2 alters the Boltzmann distribution of the other nucleus and changes the intensity of its resonance. This change in intensity is known as the Nuclear Overhauser Effect.84 The origin of NOE is illustrated in Scheme 1.15.  Scheme 1.15  Spin states and transition probabilities for a two spin system. αα ββ βα αβ W1B W1A W1B W1A W0 W2 E1 E2 E4 E3   If the total number of spins in Scheme 1.15 is N, then the population of the two intermediate levels αβ and βα can be roughly considered to be N/4. The αα state, which located at a lower level, must have a slightly higher population, which can be denoted as (N/4)+Δ, while the population of the ββ state is (N/4)-Δ. The intensity of the resonance is proportional to the difference between the population of the upper and lower spin states involved. In the NOE experiment, one resonance is irradiated with a strong decoupling B2 field, inducing transitions between the spin states concerned, which causes their populations to become equal. Then the population of states linked by W1B become equal, making the population of αβ  42 state E3 equal to that of the αα state E4 and the population of the βα state equal to that of ββ state. Consequently, Pαβ-Pαα (difference between population of αα state and αβ state) = 2Δ, while Pαβ-Pαα = Δ in the absence of a decoupling magnetic field. After the spin states, shown in Scheme 1.15, have been irradiated, they will begin to relax back to their equilibrium population. The most effective relaxation pathway is relaxing directly back from ββ to αα state (W2). The new equilibrium present with irradiation can carry spin along the route βα→ββ→αα→αβ. Increase of the population αβ and decrease of the population of βα state result in a higher resonance intensity. However, relaxation directly from βα to αβ (W0), which can also bring the system to equilibrium, will result in a lower intensity. For small molecules with molecular weight less than about 1000 Da, W0 << W2 and the increased intensity of the resonance will be observed. For larger molecules with molecular weight over 5000, W2 << W0 and decreased peak intensity or inverted peaks are expected. For some intermediate sized molecules, the NOE effect sometimes disappears. The pulse sequence for a 2D NOESY NMR experiment is presented in Scheme 1.16. After three 90º pulses, the transverse magnetization carrying NOE information can be detected and a ROESY NMR spectrum can be obtained after Fourier transformation. Compared to NOE that can be positive (small molecules), negative (large molecules) and null (medium-sized molecules), the ROE (NOE in the rotating frame) is away positive. The rotating-frame NOESY experiment (ROESY) provides advantages for the characterization of medium-sized molecules. Because the macrocycles and host-guest complexes in this thesis are medium-sized molecules (with molecular weights from 1500 to 4000 Da), 2D ROESY experiments are used for characterization.    43  Scheme 1.16  The NOESY pulse sequence.  90º 90º 90º t1 Δ t2 preparation evolution mixing detection   1.6.2 Characterization of Liquid Crystals by Polarizing Optical Microscopy (POM)  A typical setup of a polarizing optical microscope is shown in Figure 1.21. A light source is at the bottom of POM and the light is polarized by a polarizer. The liquid crystal sample is normally put on a glass slide and placed on a sample stage. When the polarized light passes into the liquid crystal sample, because of the birefringence properties of liquid crystal material, the typical liquid crystal texture can be observed by eye or recorded by a digital camera. The birefringence of LCs arises from their anisotropic nature. Birefringence occurs because the incident light is split into two components due to the existence of different refractive indices of light in different directions within these materials. When the light exits the LC, two split rays recombine, but with a different polarization than before. The color and intensity of light observed depends on the local orientation of the LC molecules, as well as the thickness of the sample.85 Liquid crystal textures observed by polarizing optical microscopy are used to identify different LC phases because each LC phase has its own characteristic texture.  44 light source mirrorlens polarizer Sample stage sample heating stage objectives analyzer ocular digital camera prism focus  Figure 1.21 Setup of a polarized optical microscope  1.7 Conclusions  Supramolecular chemistry has become much more interesting since the discovery of crown ether-metal complexes. The field of supramolecular chemistry can be split into three areas differing by the objects studied. The first is host-guest chemistry, which is the fundamental basis of this field. The second is medium-size supramolecular architectures, such as rotaxanes, catenanes and molecular cages, which possess unique shapes and supramolecular topologies. The third is aggregation-based supramolecular chemistry, such as supramolecular polymers, micelles and fibres. Many kinds of supramolecular hosts, such as calixarenes, cyclodextrins, cucurbiturils and cyclophanes, have been discovered or synthesized. These macrocycles have been used to organize different supramolecular architectures. Each host has its own advantages and limitations.  45 Synthesis of new supramolecular hosts is still necessary for meeting the needs of developing new supramolecular structures. On the basis of the present achievements in supramolecular chemistry, the future development of supramolecular chemistry is promising. As a field between chemistry, physics and biology, supramolecular chemistry will be fundamental to study the operation of living organisms at a molecular level. It will also form a basis for the creation of complex molecular devices.  1.8 Goals and Scope of This Thesis  This chapter has introduced the topic of supramolecular chemistry, and supramolecular hosts are the focal point. The long-term goal of my research was to develop new macrocycles that can be used as supramolecular hosts and to explore their assembly into medium-size architectures and huge supramolecular aggregations, such as rotaxane, catenane, liquid crystals or nanofibers. Schiff-base macrocycles have never been reported as supramolecular hosts for organic cations. I synthesized a series of [2+2] Schiff-base macrocycles (Figure 1.21), which dissolve in the common organic solvents, such as chloroform, dichloromethane and tetrahydrofuran. These macrocycles possess rectangular cavities with eight oxygen atoms arranged in a way to resemble the interior of a crown ether. NMR spectroscopy experiments, mass spectrometry and UV-Vis spectroscopy have proved that organic cations, such as pyridinium, ammonium, and paraquat derivatives can be included inside the cavities of these Schiff-base macrocycles to form host-guest complexes. Although some of the long-term objectives of this work were not achieved, this thesis describes significant strides towards those goals.    46 HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11   Figure 1.22 The [2+2] Schiff-base macrocycles.  Chapter 2 describes the synthesis and characterization of [2+2] Schiff-base macrocycles. The formation of host-guest complexes with these macrocycles was proved and association constants of these complexes were determined. Chapter 3 describes the preparation of molecular isosceles triangles, a unique shape that seldom appeared in the literature. These molecular isosceles triangles were investigated as supramolecular hosts for organic cations. Chapter 4 discusses the synthesis of naphthalene-based [2+2] Schiff-base macrocycles that undergo keto-enol tautomerism. Naphthalene-based macrocycles are supramolecular hosts for organic cations. These naphthalene-based macrocycles were found to form lyotropic liquid crystals in chloroform and 1,2-dichloroethane. Interestingly, I found the complex formed from macrocycle and cetylpyridinium also gives lyotropic liquid crystals. Chapter 5 describes my efforts on a different, but related, project to develop conjugated Schiff-base polymers using Gilch polymerization. The preparation of oligomers and model compounds are discussed. Finally, Chapter 6 presents a brief thesis summary with a look at future directions in this field. In this chapter, some work toward synthesizing a rotaxane is described.   47  1.9 References  1 Lehn, J.-M. Angew. Chem. Int. Ed. 1988, 27, 89. 2 Lehn, J.-M. Supramolecular Chemistry: Concepts and Perspectives New York: VCH, 1995. 3 Ronald, F. M. L.; Beijer, F. H.; Sijbesma, R. P.; Hooft, R. W. W.; Kooijman, H.; Spek, A. L.; Kroon, J.; Meijer, E. W. Angew. Chem. Int. Ed. 1997, 36, 969. 4 (a) Collier, C.P; Mattersteig, G.; Wong, E. W.; Luo, Y.; Beverly, K..; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science, 2000, 289, 1172. (b) Lehn, J.-M. Science 1993, 260, 1762. (c) Whitesides, G. M.; Mathias, J. P.; Seto, C. T. Science 1991, 254, 1312. (d) Cram, D. J. Angew. Chem. Int. Ed.. 1988, 27, 1009. (e) Pederson, C. J. Angew. Chem. Int. Ed. 1988, 27, 1021. 5 Balzani, V.; Credi, A.; Mattersteig, G.; Matthews, O. A.; Raymo, F. M.; Stoddart, J. F.;   Venturi, M.;. White,| A. J. P.; Williams, D. J. J. Org. Chem. 2000, 65, 1924. 6 (a) Shakhnovich, E. L.; Abkevich, V.; Ptitsyn, O. Nature 1996, 379, 96. (b) Klug, A. Angew. Chem. Int. Ed. 1983, 22, 565. 7 Simon, J.; Bassoul, P. Design of Molecular Materials, Supramolecular Engineering John Wiley & Sons, 2000. 8 Fischer, E. Ber. Dtsch Chem. Ges. 1894, 27, 2984. 9 MacLachlan, M. J.; Rose, A.; Swager, T. M. J. Am. Chem. Soc. 2001, 123, 9180. 10 Ashton, P. R..; Reder, A. S.; Spencer, N.; Stoddart, J. F. J. Am. Chem. Soc. 1993, 115, 5286. 11 Bell, T. W.; Jousselin, H. Nature, 1994, 367, 441. 12 Shimizu, K. D.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 12403. 13 (a) Klosterman, J. K.; Yamauchi, Y.; Fujita, M. Chem. Soc. Rev. 2009, 38, 1714. (b) Lawrence, D. S.; Jiang, T.; Levitt, M. Chem. Rev. 1995, 95, 2229.  48  14 Forman, S. L.; Fettinger, J. C.; Pieraccini, S.; Gottarelli, G.; Davis, J. T. J. Am. Chem. Soc. 2000, 122, 4060. 15 Kaucher, M. S.; Harrell, Jr. W. A.; Davis, J. T. J. Am. Chem. Soc. 2006, 128, 38. 16 (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495. (b) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017. 17 Gloe, K. Macrocyclic Chemistry : Current Trends and Future Perspectives Springer, 2005. 18 Luttringhaus, A.; Ziegler K, Liebigs Ann. Chem. 1937, 528, 155. 19 (a) Gokel, G. W.; Leevy, W. M.; Weber, M. E. Chem. Rev. 2004, 104, 2723. (b) Jarosz, S.; Listkowski, A. Curr. Org. Chem. 2006, 10, 643. (c) Steed, J. W. Coord. Chem. ReV. 2001, 215, 171. 20 Ghosh, K.; Yang, H.-B.; Northrop, B. H.; Lyndon, M. M.; Zheng, Y.-R.; Muddiman, D. C.; Stang P. J. J. Am. Chem. Soc. 2008, 130, 5320. 21 Gutsche, C. D. Calixarenes. Cambridge: Royal Society of Chemistry, 1989. 22 Vicens J.; Bohmer, V., Eds, Calixarenes Kluwer Academic Press, Dordrecht, 1991. 23 (a) Arduini, A.; Pochini, A; Reverbi S.; Ungaro, R. J. Chem. Soc., Chem. Commun. 1984, 981. (b) Arduini, A.; Pochini, A.; Reverbi S.; Ungaro, R.; Andreetti G. D.; Ugozzoli, F. Tetrahedron 1986, 7, 2089. 24 (a) McKervey, M. A.; Seward, E. M.; Ferguson, G.; Ruhl B.; Harris, S. J. J. Chem. Soc., Chem. Commun., 1985, 388. (b) Chang, S.-K.; Cho, I. J. Chem. Soc.: Perkin Trans. I, 1986, 211. 25 (a) Yamamoto H.; Shinkai, S. Chem. Lett. 1994, 1115. (b) Ghidini, E.; Ugozzoli, F.; Ungaro, R.; Harkerma, S.; Abu EI-Fadl, A.; Reinhoudt, D. N. J. Am. Chem. Soc. 1990, 112, 6979. 26 (a) McKittrick, T.; Diamond, D.; Marrs, D. J.; O’Hagan, P.; McKervey, M. A. Talanta, 1996, 43, 1145. (b) Malone, J. F.; Marrs, D. J.; Mckervey, M. A.; O’Hagan, P.; Thompson, N.; Walker, A.; Arnaud-Neu, F.; Mauprivez, O.; Schwing-Weill, M. –J.; Dozol, J. –F.; Rouquette, H.; Simon,  49  N. J. Chem. Soc., Chem. Commun. 1995, 2151. 27 Behrend, R.; Meyer, E.; Rusche, F. Liebigs Ann. Chem. 1905, 339, 1. 28 Freeman, W. A.; Mock, W. L.; Shih, N.-Y. J. Am. Chem. Soc. 1981, 103, 7367. 29 (a) Mock, W. L.; Shih, N.-Y. J. Org. Chem. 1986, 51, 4440. (b) Jeon, W. S.; Moon, K.; Park, S. H.; Chun, H.; Ko, Y. H.; Lee, J. Y.; Lee, E. S.; Samal, S.; Selvapalam, N.; Rekharsky, M. V.; Sindelar, V.; Sobransingh, D.; Inoue, Y.; Kaifer, A. E.; Kim, K. J. Am. Chem. Soc. 2005, 127, 12984. 30 Mock, W. L. Top. Curr. Chem., 1995, 175, 1. 31 Kim, J.; Jung, I. S.; Kim, S. Y.; Lee, E.; Kang, J. K.; Sakamoto, S.; Yamaguchi, K.; Kim, K. J. Am. Chem. Soc. 2000, 122, 540. 32 (a) Jeon, Y. J.; Kim, S.-Y.; Ko, Y. H.; Sakamoto, S.; Yamaguchi, K.; Kim, K. Org. Biomol. Chem. 2005, 3, 2122. (b) Wheate, N. J.; Buck, D. P.; Day, A. I.; Collins, J. G. Dalton Trans. 2006, 3, 451. (c) Dong, N.; Xue, S. F.; Tao, Z.; Zhao, Y.; Cai, J.; Liu, H.-C. Acta Chimi. Sin. 2008, 66, 1117. (d) Wang, R.; Macartney, D.H. Org. Biomol. Chem. 2008, 6, 1955. 33 Day, A.; Blanch, R. J.; Arnold, A. P.; Lorenzo, S.; Lewis, G. R.; Dance I. Angew. Chem. Int. Ed. 2002, 41, 275. 34 Villiers, A. Rend Acad. Sci. 1891, 112, 536. 35 Freudenberg, K.; Meyer-Delius, M. Ber. Dtsch. Chem. Ges. 1938, 71, 1596. 36 (a) Tabushi, I. Acc. Chem. Res. 1982, 15, 66. (b) Anderson, S.; Claridge T. D. W.; Anderson, H. L. Angew. Chem. Int. Ed.. 1997, 36, 1310. 37 Szejtli, J. Chem. Rev., 1998, 98, 1743. 38 (a) Miyauchi, M.; Hoshino, T.; Yamaguchi, H.; Kamitori S.; Harada, A. J. Am. Chem. Soc. 2005, 127, 2034. (b) Miyauchi, M.; Takashima, Y.; Yamaguchi H.; Harada, A. J. Am. Chem. Soc., 2005, 127, 2984. (c) Miyauchi M.; Harada, A. J. Am. Chem. Soc. 2004, 126, 11418. (d)  50  Miyauchi, M.; Kawaguchi, Y.; Harada, A. J. Inclusion Phenom. Macrocyclic Chem. 2004, 50, 57. (e) Harada, A.; Takashima, Y.; Yamaguchi, H. Chem. Soc. Rev. 2009, 38, 875. 39 Odell, B.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D. J. Angew. Chem., Int. Ed. 1988, 27, 1547. 40 Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.;Williams, D. J. J. Chem. Soc., Chem. Commun. 1991, 1584. 41 Ashton, P. R.; Odell, B.; Reddington, M. V.; Slawin, A. M. Z .; Stoddart J. F.; Williams, D. J . Angew. Chem., Int. Ed. 1988, 27, 1550. 42 Reddington, M. V.; Slawin, A. M. Z ; Spencer, N.; Stoddart, J. F.; Vicent C.; Williams, D. J. J. Chem. Soc., Chem. Commun., 1991, 630. 43 Goodnow, T. T.; Reddington, M. V.; Stoddart, J. F.; Kaifer, A. E. J. Am. Chem. Soc. 1991, 113, 4335. 44 Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart J. F. Angew Chem., Int. Ed. 2000, 39, 3348. 45 Nielsen, M. B.; Jeppesen, J. O.; Lau, J.; Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J. Org. Chem. 2001, 66, 3559. 46 Castro, R.; Davidov, P. D.; Kumar, K. A.;; Marchand, A. P.; Evanseck J. D.; Kaifer A. E. J. Phys.Org. Chem. 1997, 10, 369. 47 Cooke, G.; Daniels, L. M.; Cazier, F.; Garety, J. F.; Hewage, S. G.; Parkin, A.; Rabani, G.; Rotello, V. M.; Wilson, C. C.; Woisel P. Tetrahedron 2007, 63, 11114. 48 Rajakumar, P.; Sekar, K. Tetrahedron Lett. 2006, 47, 4023. 49 Harrison, I. T.; Harrison, S. J. Am. Chem. Soc. 1967, 89, 5723. 50 Glink, P. T.; Oliva, A. I.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem. Int. Ed. 2001, 40, 1870. 51 Schiff, H. Annalen 1864, 131, 118.  51  52 Calligaris, M.; Randaccio, L. Comprehensive Coordination Chemistry Pergamon Press, 1987. 53 Gupta, K.C.; Sutar, A. K. Coord. Chem. Rev., 2008 252, 1420. 54 Star, A.; Goldberg, I.; Fuchs, B. J. Org. Chem. 2001, 630, 67. 55 (a) Sun, S.-S.; Stern, C. L.; Nguyen, S. T.; Hupp, J. T. J. Am. Chem. Soc. 2004, 126, 6314. (b) Kleij, A.W.; Kuil, M.; Lutz, M.; Tooke, D. M.; Spek, A. L.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Inorg. Chim. Acta. 2006, 359, 1807. 56 Hui, J. K.-H.; Yu, Z.; MacLachlan, M. J. Angew. Chem. Int. Ed. 2007, 46, 7980. 57 Borisova, N. E.; Reshetova, M. D.; Ustynyuk, Y. A. Chem. Rev. 2007, 107, 46. 58 Pilkington, N. H.; Robson, R. Aust. J. Chem. 1970, 23, 2225. 59 Bell, M.; Edwards, A. J.; Hoskins, B. F.; Kachab, E. H.; Robson, R. J. Am. Chem. Soc. 1989, 111, 3603. 60 Gallant, A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2003, 42, 5307. 61 Gallant, A. J.; Yun, M.; Sauer, M.; Yeung, C. S.; MacLachlan, M. J. Org. Lett. 2005, 7, 4827. 62 (a) Bahadur B., eds., Liquid Crystals-Application and Uses,World Scientific, Singapore, 1990. (b) Demus, D.; Goodby, J.; Gray, G. W.; Spiess, H.W.; Vill V., eds., Handbook of Liquid Crystals Wiley-VCH, Weinheim, 1998. 63 (a) Collings, P.; Hird, M. Introduction to Liquid Crystals,Taylor & Francis, 1997). (b) Hegmann, T.; Qi, H.; Marx, V. M. J. Inorg. Organomet. Polym. Mater. 2007, 17, 483-508. 64 (a) Tschierske, C. Prog. Polym. Sci. 1996, 21, 775. (b) Tschierske, C. J. Mater. Chem. 1998, 8, 1485. 65 Chandrasekhar, S.; Sadashiva, B. K.; Suresh, K. A. Pramana 1977, 9, 471. 66 (a) Xiao, S.; Myers, M.; Miao, Q.; Sanaur, S.; Pang, K.; Steigerwald, M. L.; Nuckolls, C. Angew. Chem., Int. Ed. 2005, 44, 7390. (b) Schmidt-Mende, L.; FechtenkRtter, A.; Mqllen, K.; Moons, E.; Friend, R. H.; Mackenzie, J. D. Science 2001, 293, 1119.  52  67 Niori, T.; Sekine, T.; Watanabe, J.; Furukawa, T.; Takezoe, H. J. Mater. Chem. 1996, 6, 1231. 68 (a) Etxebarria, J.; Ros, M. B. J. Mater. Chem. 2008, 18, 2919. (b) Kumar, S. Chem. Soc. Rev. 2006, 35, 83. 69 Demus, D.; Goodby, J.; Gray, G. W.; Spiess, H. W.; Vill, V., eds., Handbook of Liquid Crystals, Vol. 2a, Wiley-VCH, Weinheim, 1998. 70 Reddy, R.; Tschierske, C. J. Mater. Chem. 2006, 16, 907. 71 J. M. Seddon, R. H. Templer, Phil. Trans. R. Soc. Land. A. 1993, 344, 377. 72 Radley, K.; Reeves, L. W.; Tracey, A. S. J. Phys. Chem. 1976, 80, 174. 73 Nesrullajev, A.; Kazanci, N. Mater. Chem. Phys. 2000, 62, 230. 74 (a) Freeman, W. A. Acta. Cryst. B. 1984, 40, 382. (b) Day, A. I.; Blanch, R. J.; Arnold, A. P.; Lorenzo, S.; Lewis, G. R.; Dance, I. Angew. Chem. Int. Ed. 2002, 41, 275. 75 (a) Yamashita, M.; Fenn, J. B. J. Phys. Chem. 1984, 88, 4451. (b) Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989, 246, 64. 76 (a) Karas, M.; Bachmann, D.; Bahr, U.; Hillenkamp, F. Int. J. Mass Spectrom. Ion Proc. 1987, 78, 53. (b) Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Rapid Commun. Mass Spectrom. 1988, 2, 151. 77 Brodbelt, J. S. Int. J. Mass Spectrum. 2000, 200, 57. 78 Brodbelt J. S.; Dearden, D.V. Comprehensive Supramolecular Chemistry, 1996, 8, 567. 79 Macomber, R. S. J. Chem. Ed. 1992, 69, 375. 80 Connors, K.A. Binding Constants, Wiley Interscience, New York, 1987. 81 Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311. 82 Huang, C.Y. Methods Enzymol. 1982, 87, 509. 83 Overhauser, A.W. Phys. Rev. 1953, 92, 411. 84 Slichter, C. P. Principles of Magnetic Resonance. Third Edition, 1996, Springer: New York.  53  85 Dierking, I Textures of Liquid Crystals, Wiley-VCH, Weinheim, 2003.        54 Chapter 2  Host-guest Chemistry of [2+2] Schiff-base Macrocycles*  2.1 Introduction  Since the first reports of crown ethers and discovery of their ability to complex alkali metals,1 host-guest chemistry has rapidly developed into an expansive field of research.2,3 Diverse macrocycles, including cryptands,4 cucurbit[n]urils,5 calixarenes6 and cyclodextrins7 have been investigated in the context of host-guest chemistry and molecular recognition.8 The ability to modify the macrocycle’s shape, size, and functionality is critical for developing strong and selective binding of guests. Host-guest interactions have recognized importance in many biological processes, including enzyme catalysis and inhibition, membrane transport and antibody-antigen interactions.9 A particularly fruitful field of organic synthesis in recent years has been the design and preparation of macrocyclic hosts for cation binding to mimic biological host-guest interactions. Cation binding is prevalent in many chemical and biological systems; it plays central roles in molecular recognition, stabilization of protein and nucleic acid structures, and in their biological functions.10  * A version of this chapter has been published: (a) Frischmann, P. D.; Jiang, J.; Hui, J. K.-H.; Grzybowski, J. J.; MacLachlan, M. J. "The Reversible-Irreversible Approach to Schiff Base Macrocycles: Access to Isomeric Macrocycles With Multiple Salphen Pockets", Org. Lett. 2008, 10, 1255. (b) Jiang, J.; MacLachlan, M. J. "Cationic Guest Encapsulation in Widemouthed Schiff Base Macrocycles" Chem. Commun. 2009, 5695.   55 Schiff base macrocycles, generally formed from the condensation of a diamine and a dialdehyde or diketone, are an interesting class of macrocycles with highly tunable structures. With choice of precursors, diverse structures with different geometries may be obtained.11-12 Owing to their relative ease of synthesis and excellent metal complexing properties, Schiff-base macrocycles have been developed for coordination chemistry, and most studies have focused on their use for supporting molecular magnetic materials13  and catalysts. 14  Although several researchers have investigated the supramolecular chemistry of Schiff base macrocycles with respect to liquid crystallinity15 and aggregation,10i, 10k it is surprising that with the exception of metal binding, the host-guest chemistry of Schiff base macrocycles has been seldom explored. Pyrrole-containing Schiff base macrocycles have demonstrated anion and neutral guest recognition through hydrogen-bonding, 16  and boron-based macrocycles with Schiff base substituents have shown host-guest properties.17 In this chapter, the formation of host-guest complexes by using Schiff-base macrocycles as supramolecular hosts is described. A new macrocycle with a rectangular cavity to accommodate organic cations has been designed and studied.  2.2 Results and Discussion  2.2.1 Synthesis and Characterization of [2+2] Schiff-base Macrocycles 35  I set out to construct new rectangle-shaped [2+2] macrocycles based on previous work in our lab ([n+n] refers to the combination of n precursors each having two aldehyde groups and n  56 precursors each having two amino groups). Through an easy aldimine-forming Schiff-base reaction, our group has reported the synthesis of a triangular [3+3] macrocycle 2718 and a hexagonal [6+6] macrocycle 33 (Figure 2.1). 19  In the synthesis of macrocycle 33, an intermediate compound 32 was reacted with 4,6-diformylresorcinol 31 to obtain the [6+6] macrocycle by Schiff-base condensation. With a similar strategy, we proposed to synthesize a rectangular [2+2] macrocycle 34 by reacting 32 with 2,3-dihydroxyl-1,4-diformylbenzene 25. However, the NMR spectrum of the product shows there are many impurities accompanied with the desired compound and it was very difficult to purify. The failure of the synthesis is attributed to the reversible nature of aldimine in intermediate 32. To overcome the reversibility of aldimine on 32, we designed a ketimine precursor 39 (Scheme 2.2) which is much more kinetically stable than an aldimine to replace the aldimine precursor 32 and finally obtained the [2+2] macrocycle 35.  57 N N OH OH HO HO N N N N HO OH RO OR OR RO RO OR N N OHHO N HO OH N N N OH OH OH HO N N N N OH OH OH HO N N OR OR OR RO RO RO RO OR OR OR OR OR N N N N OH OH HO HO HO OH N N N N HO OH OR RO OR OR OR OROR RO N N N N OH OH HO HO HO OH N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 OC5H11 OC5H11H11C5O H11C5O 27 33 34 35 Figure 2.1 Structure of Schiff-base macrocycles. In order to synthesize the hydrolysis-stable ketimine precursor 39, a diketone compound 36, 4,6-dihydroxyl-1,3-dibenzoylbenzene, must be prepared first. Compound 36 was synthesized by literature methods as shown in Scheme 2.1.20 This reaction involves a demethylation followed by a Friedel-Crafts acylation reaction.  Scheme 2.1 Synthesis of precursor 36. HO OH O OMeO OMe + O Cl 1. AlCl3, CH2Cl2 2. H2O/H+ 32 33 34637 38  It is known that the condensation of diphenyl ketone with phenylenediamine stops after only  58 one of the amines has reacted unless harsh conditions are utilized.21  Ketimine-containing precursor 39 (Scheme 2.2) was synthesized via a solid-state reaction. By melting the mixture of 36 and 40 under nitrogen with a heatgun (around 210 ºC) for 5 minutes, an air stable yellow solid was obtained after separation. The yield of this reaction is not high (22%) due to poor mixing in the viscous liquid formed during the reaction.  Scheme 2.2 Synthesis of precursor 39.  34 35 36 HO OH O O + H2N NH2 H11C5O OC5H11 HO OH N N NH2 NH2 H11C5O H11C5O OC5H11 OC5H11 solid state2 396 40  For synthesizing 39, the solid-state reaction proved to be an effective method. Before finding the solid-state reaction, I tried to synthesize this compound in solution with different solvents and catalysts, but all of these reactions failed. Because of its stability to hydrolysis, compound 39 can be used as a precursor for the synthesis of macrocycles without worrying about decomposition. The 1H NMR spectrum of 39 shows there is a very strong O–H…N hydrogen bond formed and the hydroxyl resonance shifts from 12.88 ppm in 36 to 15.74 ppm in 39 (in CDCl3). The NH2 resonance is observed at 3.69 ppm and this peak remained unchanged after 39 was kept in air for 1 year, indicating that the amino group on this compound is air stable (the amino groups on 40 can be oxidized in air in several minutes).    59  H H H HH H H H HHHHO OH N N Ph H H11C5O OC5H11 H11C5O H OCH2C4H9H H NH2 NH2 Ha b H   Figure 2.2 1H NMR spectrum (300 MHz, CDCl3) of 39.   The peaks at 6.82 and 6.60 ppm are attributed to Ha and Hb (Figure 2.2), respectively. A deuteration method was used to assign these two peaks. Deuterations of aromatic protons on resorcinols have been reported in some papers.22 The proton (corresponding to Ha) between the two hydroxyl groups was found to be easily deuterated at an elevated temperature. However deuteration of the proton at meta position to hydroxyl groups (corresponding to Hb) is very difficult. Based on these observations, compound 39 was dissolved in a mixture of CDCl3 and CD3OD. After heating at 50 ºC for three hours, the 1H NMR spectrum showed that the peak at 6.60 ppm had almost disappeared, while the peak at 6.82 was unchanged (Fig 2.3). This experiment indicates that the Ha resonance is at 6.60 ppm.   60 39 39 after deuteration   Figure 2.3 Comparison of the 1H NMR spectra of 39 before and after deuteration (400MHz, 298K, CDCl3:MeOD = 20:1).  Condensation of 39 and 25, with piperidine as catalyst, afforded red, microcrystalline solid product 35 in a decent yield, 35% (Scheme 2.3)  Scheme 2.3 Synthesis of macrocycle 35. HO OH N N NH2 NH2 H11C5O H11C5O OC5H11 OC5H11 + OH OH O O piperidine CHCl3/MeCN refluxing overnight HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 2 2 39 25 35 The matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum of macrocycle 35 shows a single peak at 1946.4, corresponding to its structure. The IR spectrum confirms a single imine functionality with the C=N stretch observed at 1615 cm-1, and no  61 aldehyde C=O absorption from the starting material 25 (1660 cm-1). The 1H NMR spectrum of 35 (shown in Figure 2.3) shows only one imine (δ = 8.36) and two singlet hydroxyl resonances (δ = 15.18, 12.90 ppm), consistent with an average D2h symmetry of the macrocycle. The 13C NMR spectrum of 35 is also consistent for the macrocycle structure with two imine resonances found at 173.5 and 161.5 ppm. This macrocycle contains four equivalent N2O2 pockets (N2O2 pocket refers to a binding site that has two N-donor atoms and two O-donor atoms available for coordination to a metal), each incorporating one aldimine and one ketimine. This low symmetry in a single N2O2 pocket is useful for developing chirality in metal complexes23 which might in turn influence the products of catalysis. Despite the appeal of unsymmetrical N2O2 pockets, the synthesis of such macrocycles is rarely reported due to the lack of methodology to make Schiff base macrocycles possessing them.  2.2.1.1 Assignment of 1H NMR Peaks of Macrocycle 35.  There are two hydroxyl peaks, several aromatic peaks and two –OCH2- peaks in the NMR spectrum of 35. To study the properties of this macrocycle, it was first necessary to assign most of the protons in the NMR spectrum for macrocycle 35. To assign these peaks, the 2D ROESY NMR spectrum of 35 and a resorcinol deuteration reaction were used. Shown below is the 1-D NMR spectrum (Figure 2.4 and 2.5).  62 HO OH N N N N H11C5O H11C5O O O OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 Ph Ph H H a b c d He Hf Hk Hl PhH H H H C C4H9 Hm HC C4H9 Hn o p q    Figure 2.4 1H NMR Spectrum of macrocycle 35 (400 MHz, 298K, CDCl3).   Figure 2.5 1H NMR Spectrum of the macrocycle 35 between 6.5-7.1 ppm.  63  Macrocycle 35 was synthesized from a resorcinol-containing precursor 39 and 3,6-diformylcatechol 25. The chemical shift of hydroxyl protons of resorcinol-containing precursor 39 is 15.74 ppm, while previous reports of macrocycles made from 3,6-diformylcatechol 25 always have OH proton resonances near 13 ppm24 in CDCl3. Based on these, the peaks at 15.19 ppm and 12.90 ppm in the 1H NMR of macrocycle 35 are assigned to resonances of Ha and Hb, respectively. The peak at 8.36 ppm is the imine resonance (Hc). The peaks at 6.54 and 6.88 ppm were assigned the resonances of Hd and Hk. In order to establish which peak was attributed to Hd, a deuterium exchange experiment was performed. Upon exposure to MeOH-d4 at elevated temperature, the proton at 6.54 ppm decreases in intensity relative to the other protons; the exchange of protons on benzene rings in resorcinol-based species has been observed previously. There are three singlets between 6 and 7 ppm whose integrations are around 1.0. The chemical shifts of these three peaks are 6.84, 6.62 and 6.14 ppm, which must correspond to He, Hf and Hl. Because only He was shielded by a phenyl ring, the signal at 6.14 ppm is assigned to He. For the assignment of peaks f and l, I resorted to the 2D-ROESY spectrum shown in Figure 2.6b. In Figure 2.6b, there is a spin coupling between the signals at 6.62 and 3.92 ppm which corresponds to the –OCH2- of the pentyloxyl chain. However, no coupling was found between the peak at 6.84 ppm and the signal assigned to –OCH2-. Therefore, the proton corresponding to the signal at 6.62 ppm is near to the –OCH2- group, which was attributed to Hf in macrocycle 35. The signal at 6.84 ppm in the macrocycle was thus assigned to Hl. There are two kinds of –OCH2- protons, whose signals appear as triplets at 3.92 and 3.59  64 ppm. From the 2D-ROESY in Figure 2.6, the more downfield signal coupled with resonance of Hf. Therefore, the signal at 3.92 ppm is assigned to Hm. The peak at 3.59 ppm coupled with resonance of He, and so it is assigned as the signal of Hn. There are three kinds of protons on the mono-substituted phenyl ring that is attached to the ketimine, i.e., Ho, Hp and Hq. The resonances of Ho, Hp and Hq should be a doublet, triplet and triplet, respectively. In addition, the integration of signal of Hq should be half of the other two protons. From the above information, peaks o, p and q are attributed to Ho, Hp and Hq, respectively. (a) (b) b c o b c o (b,c) (c,o)  Figure 2.6 (a) 2D-ROESY spectrum of macrocycle 35 with a mixing time of 120 ms (400 MHz, CDCl3, 298K). (b) Enlarged spectrum from 2.8 ppm to 4.5 ppm (F1) and from 5.5 ppm to 7.4 ppm (F2).      65 2.2.1.2 Simulations of Macrocycle 35  Although macrocycle 35 was fully characterized by NMR, MALDI-TOF MS, IR, UV-Vis and EA, its conformation in space is still not clear. 2D-ROESY data indicates it is in a cone-like structure instead of a coplanar conformation (the resonance coupling between b and c; coupling between c and o in Figure 2.6a). To verify the result of the 2D-ROESY spectrum, I attempted to grow single crystals of this compound. Unfortunately, no single crystals were obtained even with changing to different alkyl chains on the phenylenediamine moieties and using different solvents. To study the conformation of macrocycle 35, we resorted to computation. Given the large size of the macrocycle in this study, its flexibility, and the number of interactions involved (hydrogen-bonding, π-π stacking, electrostatic), detailed DFT calculations were beyond the scope of the study. However, semi-empirical calculations (PM3) were employed to estimate the size of the macrocycles and to determine the conformations that could be reasonably expected. Calculations were performed on macrocycles 35 using Spartan ’04 for Windows (note that peripheral alkoxy groups were removed for simplification as they are not expected to significantly affect the conformation). Simulations were started from several different likely conformations and minimized. Figures 2.7 show a series of energy-minimized structures obtained from semi-empirical calculations of macrocycles 35, along with the energies. There may be additional conformations representing minima on a complex conformational landscape, but these are representative stable conformations.    66  E = 116.84 kcal / mol “all hydroxyls up” E = 113.67 kcal / mol “one meta-dihydroxy down” E = 113.83 kcal / mol “1,2-alternate” E = 110.96 kcal / mol “one ortho-dihydroxy down” (a) (c) (b) (d) E = 16 kcal / mol E = 113 kcal / mol E = 113 kcal / mol E = 110 kcal / mol Figure 2.7 Representative energy-minimized conformations of macrocycle 35 as deduced by semi-empirical (PM3) calculations. The energy of the conformation is shown beneath each structure (nomenclature from calixarene chemistry).  2.2.2 Synthesis and Characterization of [2+2] Schiff-base Macrocycles 38 and 43.  Using a similar strategy to the synthesis used to make macrocycle 35, its isomeric macrocycle 41 was prepared as shown Scheme 2.4. Macrocycle 41 was obtained via Schiff-base condensation of ketimine-containing compound 42 and 4,6-diformylresorcinol 31.       67   Scheme 2.4 Synthesis of macrocycle 41.  HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 piperidine CHCl3/MeCN refluxing overnightHO OH N N NH2 H2N OC5H11 OC5H11 H11C5O H11C5O + HO OH OO2 2 37 25 38 42 31 41 Macrocycle 41 was created via the formation of four aldimine bonds and was isolated in 41% yield. The structure of the macrocycle was verified by MALDI-TOF mass spectrometry and NMR spectroscopy. The presence of a peak at 1947.5 ([M+H]+) in the MALDI-TOF mass spectrum indicates the product has the same mass as our desired structure. The 1H NMR spectrum of 41 (Figure 2.8) exhibits only one imine (δ = 8.26 ppm) and two singlet hydroxyl resonances ( 14.42, 13.91 ppm), which indicate its average D2h symmetry.  * ppm HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 H a b c Hd a b c d  Figure 2.8 1H NMR spectrum of macrocycle 41 (400 MHz, CDCl3, 298K).  68  Like its isomer 35, there are four unsymmetrical N2O2 pockets in 41. Simulation of this molecule by Spartan’ 04 affords a similar cone-like structure to that of 35, as shown in Figure 2.9. Variable Temperature NMR (VT-NMR) spectroscopy shows the exchange between conformations of 41 or 35 are so fast on 1H NMR time-scale that no distinct conformations could be resolved even though the temperature was decreased to -80°C.  E = 110.23 kcal / mol “twisted 1,3-alternate” E = 110.90 kcal / mol “flattened 1,3-alternate” E = 112.83 kcal / mol “1,2-alternate” E = 112.44 kcal / mol “one ortho-dihydroxy down” E = 10 kcal / mol E = 111 kcal / mol E = 113 kcal / mol E = 110 l / l  Figure 2.9 Representative energy-minimized conformations of macrocycle 41 as deduced by semi-empirical (PM3) calculations. The energy of the conformation is shown beneath each structure.  Precursor 42 was prepared by Peter Frischmann in our lab. The synthesis route to 42 is shown in Scheme 2.5. By condensation of benzoin with catechol 43 at 260 °C,  69 tetraphenyl-o-benzodifuran 44 was isolated in 25% yield. Oxidation with CrO3 followed by hydrolysis of the benzoate ester gave 45. 25  Compound 45 reacted with dialkoxyphenylenediamine in solution to give precursor 42 in a 33% yield. In addition, precursor 42 can also be prepared via a solid-state reaction. By mixing 45 and dipentyloxyphenylenediamine 40 together and then reacting with this solid-state method, compound 42 was obtained in a similar yield to the solution route (33%). It is interesting that compound 39, the isomer of 42, could not be obtained in solution, and 39 can only be prepared with the solid-state reaction. The reason for this difference is not clear.  Scheme 2.5 Preparation of precursor 42. HO OH benzoin, B2O3 260 oC 10 min O O Ph Ph Ph Ph 1) CrO3, AcOH 2) H2SO4 OH OH O O Ph Ph 39 40 41 OH OH O O Ph Ph + H2N NH2 OC5H11H11C5O piperidine toluene, reflux HO OH N N NH2 H2N H11C5O H11C5O OC5H11 OC5H112 41 375 42 43 44 45 40  Compound 42 is a very useful precursor and it can react with multi-aldehyde-containing compounds to form macrocycles or polymers. This compound was also used to synthesize another rectangular [2+2] macrocycle 46 that contains 10 hydroxyl groups by taking advantage  70 of the shape of 42 (Scheme 2.6).  Scheme 2.6 Synthesis of macrocycle 46. piperidine CHCl3/MeCN refluxing overnightHO OH N N NH2 H2N OC5H11 OC5H11 H11C5O H11C5O + HO OH OO OH HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 OH OH2 2 37 42 4346 42 47   The structure of macrocycle 46 is identical to macrocycle 41 except for 2 extra hydroxyl groups in the interior. The resonances of the two hydroxyl groups partially appear in the 1H NMR spectrum (Figure 2.10) when the deuterated solvent is very dry. Because the resonance of the extra hydroxyl groups is located at 8.55 ppm, there should be weak hydrogen bonding formed among the three hydroxyl groups on each trihydroxyl benzene moiety.     71 HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 OH OH a b c HdHe a * bc d e  Figure 2.10 1H NMR spectrum of macrocycle 46 (400MHz, CDCl3, 298K).  2.2.3 Host-Guest Chemistry of Schiff-base Macrocycles  2.2.3.1 1:1 and 1:2 Complexes Formed by Schiff-base Macrocycles and Their Guests  Isomeric Schiff base macrocycles 35 and 41 are readily synthesized through a sequence of ketimine condensation followed by aldimine condensation. Semi-empirical calculations of the two macrocycles showed that they are rather flexible and can adopt several stable cone-like conformations with large cavities in the center. The calculations reveal large, rectangular cavities in each of the macrocycles with dimensions of ca. 1.00 x 1.05 nm for macrocycle 35 (measured from the centroids of the benzene rings in the conformation depicted in Figure 2.6a and 1.23 x 0.93 nm for macrocycle 41. These cavities are much bigger than those of most of the commonly used macrocyclic hosts, i.e., cucurbit[6]uril (0.39 nm diameter),26, 27 cucurbit[7]uril (0.54 nm  72 diameter),28 cucurbit[8]uril (0.69 nm diameter),28 α-cyclodextrin (0.49 nm diameter), 28 β-cyclodextrin (0.62 nm diameter), γ-cyclodextrin (0.79 nm diameter), calix[4]arene (0.38 nm diameter of upper-rim)29 and calix[6]arene (0.50 nm diameter of upper-rim).30 The large size of the cavities suggested that these macrocycles could function as hosts for guest molecules. In addition, calculations show that the Schiff-base macrocycles are quite flexible, and thus may adjust their conformations according to the size and shape of guests to enhance binding. With these features in mind, we sought to investigate the host-guest chemistry of the macrocycles. Macrocycle 35 is not very soluble in a mixture of chloroform and methanol, but its solubility improves dramatically upon addition of cetylpyridinium chloride (CPC) 48+·Cl-. Moreover, there was a minor color change to the solution. These observations led us to explore the binding of cetylpyridinium and other organic cations to these macrocycles. Upon addition of CPC to a solution of 35, the absorption band of macrocycle 35 undergoes a small red-shift from 392 nm to ca. 395 nm. As larger changes were observed by 1H NMR spectroscopy, this technique was used for the characterization of binding properties. Figure 2.11 shows the changes to the 1H NMR spectrum of 35 that occur upon addition of CPC. Peak shifts of 0.83 and 1.11 ppm were observed for signals of Hb and Hd, respectively, suggesting a binding event had occurred. Other peaks attributed to protons of the macrocycle and CPC also moved upon mixing. Very similar shifts were observed for macrocycle 41.   73 1 3+·Cl- HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO N N N N HO OH H11C5O H11C5O OC5H11 OC5H11 Ph Ph H a b c He Hf N HC C15H31 H gH H H h i j Cl- PhPh Hd 31 44+·Cl- 5 48+Cl-   Figure 2.11 1H NMR spectra of (a) cetylpyridinium chloride (48+·Cl-); (b) mixture of macrocycle 35 and cetylpyridinium chloride ([CPC]:[1] = 5:1); and (c) macrocycle 35 (400 MHz, CDCl3, 298 K). The peaks are assigned as shown in the molecular structures above the spectra.  The downfield shifts observed for hydroxyl protons Ha and Hb suggest that the cetylpyridinium interacts with the oxygen atoms of the hydroxyl groups on the interior of the macrocycle. This conclusion was verified by the 2D-ROESY spectrum (Figure 2.12; the peaks are assigned in the molecular structure in Figure 2.11), which revealed through-space spin couplings between Ha and Hg, Hb and Hg, Hb and Hh, Hd and Hh. These connections indicate that the charged headgroup of cetylpyridinium is bound inside the cavity of macrocycle 35, forming a host-guest complex of macrocycle 35 and 48+ (48+ ⊂ 35 complex). In addition, couplings  74 between Ha and He, Hb and Hf are also observed, suggesting the macrocycle adopts a 3-D cone-like structure instead of a planar geometry, in agreement with predictions from semi-empirical calculations. Strong coupling between Ha and Hb in the ROESY spectrum of the 48+ ⊂ 35 complex indicates that all hydroxyl groups in macrocycle 35 must be oriented on the same side of the cone, at least in one conformation of the host-guest complex. Figure 2.13 shows an energy minimized simulation of the 48+ ⊂ 35 complex. In every calculated structure, the pyridinium ring is most stable when it is co-facial with the resorcinol rings. In this model, the hydrogen atom Hd is situated ca. 3.1 Å over the pyridinium ring, where it would be expected to experience additional shielding upon binding the guest. In fact, this proton resonance moves upfield from 6.53 ppm in macrocycle 35 to 5.42 ppm in the 48+ ⊂ 35 complex. Furthermore, in this orientation, Hh and Hg are close enough to Hb for ROE contact (with a little movement of the guest) even though the catechol units, which contain Hb, are farther away from the centre of the cavity than are the resorcinol units. The advantage of this orientation is that both electron rich resorcinol moieties can participate in π-π interactions with the heterocyclic ring of cetylpyridinium.     75  Figure 2.12 2D-ROESY spectrum of the host-guest complex formed by macrocycle 35 and cetylpyridinium chloride 48+·Cl- with a mixing time of 120 ms (400 MHz, CDCl3, 298 K).   76 (b) (c) (a)   Figure 2.13 Energy-minimized (PM3) model of 48+ ⊂ 35 complex (a) space-filling view from bottom; (b,c) side views (The alkoxy chains of the macrocycle were removed for calculation and the alkyl chain of the pyridinium was truncated to ethyl.).  In the 2D-ROESY NMR spectrum of the inclusion complex formed by macrocycle 41 and 48+, no ROE correlation was observed between the hydroxyl proton on the resorcinol units and the hydroxyl proton on the catechol units (Figure 2.14). From comparison of the ROESY spectra of 48+ ⊂ 35 complex (shown in Fig. 2.12), one can conclude that macrocycle 41 in the 48+ ⊂ 41 complex is in an alternate cone-like structure, with hydroxyl groups of the resorcinol unit on one end of the cone, and those of the catechol groups on the other. This is supported by semi-empirical calculations. In the lowest energy structures computed, the macrocycle adopts an alternate cone-like structure, with the pyridinium ring co-facial with the resorcinol rings.  77  Figure 2.14 2D-ROESY spectrum of complex formed by macrocycle 41 and cetylpyridinium chloride 48+Cl- with a mixing time of 120 ms (400 MHz, CDCl3, 298K).  MALDI-TOF mass spectrometry provided further evidence of the host-guest complexes. Figure 2.15 shows the MALDI-TOF mass spectrum of complex 48+ ⊂ 35 exhibiting two peaks at m/z = 1946.8 and 2251.0 a.m.u.; these are assigned to macrocycle 35 and the 48+ ⊂ 35 complex, respectively. The spectrum also confirms the stoichiometry of the inclusion complex is 1:1. The formation of 1:1 inclusion complexes for 48+ ⊂ ⊂35 and 48+ 41 was also verified with Job plots constructed from 1H NMR spectroscopic experiments, Figure 2.16.  78 31+ [31+44]+ 35+ 5+48+]+   Figure 2.15 MALDI-TOF mass spectrum of host-guest complex 48+ ⊂ 35. mole fraction of macrocycle 1 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 (a) mole fraction of macrocycle 2 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .02 .04 .06 .08 .10 (b) mol  fr ti  f acrocycle 31 mole fraction of macrocycle 38mole fraction of macrocycle 35 mole fraction of macrocycle 41 Figure 2.16 Job plots of (a) 48+ ⊂ 35 and (b) 48+ ⊂ 41 (400 MHz, CDCl3, 298 K).  To better understand the complexing capabilities of macrocycles 35 and 41, we studied the  79 binding of other related molecules that could be potential guests, including cetyltrimethylammonium bromide, tetrabutylammonium bromide and methyl viologen dichloride (49-51 in Figure 2.17). 1H NMR spectroscopic experiments show these cationic compounds bind inside the cavity of Schiff-base macrocycles 35 and 41. However, neutral molecules such as pyridine, triethylamine, and 4,4’-bipyridine (53-55) are not bound by either macrocycle. Although tetraphenylphosphonium (52+) is cationic, it does not bind to the macrocycles as it is too large to fit in the cavity of either macrocycle. Therefore, the binding of organic molecules within Schiff-base macrocycles displays selectivity based on charge and size.  N C16H33 Cl- N C16H33 Br- nBu4N+Br- N N 2Cl- P Br- N NEt3 N N NN N N Br- Br- 3+ · Cl - 4+ · Br - 5+ · Br - 62+ · 2Cl - 7+ · Br - 8 9 10 112+ · 2Br - 44+·Cl- 45+·Br- 46+·Br- 472+·Cl2- 48+·Br- 49 50 51 52+·Br2- 48+Cl- 49+Br- 50+Br- 512+Cl22- 52 Br- 53 4 5 62 Br22+  Figure 2.17 Molecules investigated as potential guests for macrocycles 35 and 41.  Binding constants were determined by a nonlinear curve-fitting procedure for the guest-induced chemical shifts of selected peaks.30 The 1H NMR spectroscopic experiments involved titration of a guest solution into a host solution until no significant change in chemical  80 shift was observed in successive 1H NMR spectra. The binding constants of complexes formed by macrocycles and guests are listed in Table 2.1.  Table 2.1 Binding constant (Kassoc) of the complexes formed by association of macrocycles and guests at 300 K in CDCl3 (The concentration of hosts was kept constant at 1.28×10-3 M during titration.). guest 48+ guest 49+ guest 50+ guest 512+[a] Kassoc ( M-1) Kassoc ( M-1) Kassoc ( M-1) Kassoc ( M-1) macrocycle 35 1.85±0.37×104 3.24±0.41×103 1.20±0.60×103 2.31±0.43×105 macrocycle 41 1.48±0.18×103 1.45±0.20×103 2.28±0.11×102 1.23±0.47×105 [a] the solvent pair, CDCl3 : CD3OD = 3 : 1, was used during the titration of guest 512+ into macrocycles 35 and 41 as [512+]Cl2 is insoluble in CDCl3. From Job plots, it is clear that methyl viologen 512+ forms 1:1 complexes with macrocycles 35 and 41. Methyl viologen 512+ exhibits the highest binding constant among the four guests tested, which may be attributed to its doubly-charged nature. In addition, the binding may be enhanced by π-π interactions between heterocyclic rings of viologen and the electron rich resorcinol units of the macrocycles. The binding constants of methyl viologen with macrocycles 35 and 41 are almost equivalent to that observed for cucurbit[7]uril binding methyl viologen in aqueous solution.31 The Kassoc values for binding of 50+ ⊂ 35 and 50+ ⊂ 41 are smaller than those of 49+. This result indicates that the internal cavity of 35 and 41 is size selective when binding peralkylated ammonium cations. Similar selectivity of ammonium cations based on size was also found for cucurbit[7]uril.32 Comparison of association constants for complexes formed by macrocycles 35 and 41 (Table 2.1) show that Kassoc values for 35 are slightly bigger than those  81 for 41, and this may be a consequence of the different conformations adopted by the two macrocycles. Because the counter-anions of the guests used in this study are not same, I also studied the effect of anion to the binding constant of complex. When 50+·PF6- is titrated into macrocycle 35, the Kassoc value is 1.04 ± 0.73×103 M-1, which is identical (within error) to the binding of 50+·Br- into 35 (Kassoc = 1.20 ± 0.60×103 M-1). Though it is not possible to eliminate anion effects in every case, and ion pair binding is well known,33 it is most likely that the binding is dominated by the cation in this case. Whereas the monocationic guests and methyl viologen form 1:1 complexes with the Schiff base macrocycles, 2:1 (host:guest) complexes formed with dicationic guests if the two positive charges of the guests are sufficiently separated in space. Compound 562+·2Br- contains two positively-charged pyrazinium groups separated by a pentylene chain. In the titration of macrocycle 35 with 562+·2Br-, interesting resonance shifts were observed in the 1H NMR spectra as shown in Figure 2.18a. As the concentration of 562+ increased, the separation of two peaks centered at 9.2 ppm, which are assigned to the two distinct aromatic protons of 562+, grows and then diminishes. The expansion in Figure 2.18b shows that the resonance corresponding to Hd (structure of macrocycle 35 was shown in Fig. 2.11) shifts upfield at first, then shifts back downfield when the ratio of 562+ exceeds 1:1. The Job plot (Fig. 2.19) indicates the stoichiometry of the complex is 2:1 (host:guest); that is, two macrocycles encapsulate 562+, presumably one on each pyrazinium group. Formation of 562+ ⊂ 352 complex explains the 1H NMR spectral shifts. Because the complex was assembled by electrostatic interactions, fast exchange exists between complexed macrocycles and uncomplexed macrocycles. Addition of  82 excess of dicationic compound 56 results in the formation of some 1:1 host-guest species. For these 1:1 complexes, the macrocycle could either be threaded on the centre portion of dicationic compound or capped on the end of 56. The conformation that macrocycle caps on the end of the dumbbell-shaped guest is believed to be the main component due to the electrostatic attraction, as shown in Figure 2.20.  ppm (a) (b)  Figure 2.18 (a) The 1H NMR spectra (3:1 CDCl3/CD3OD) of macrocycle 35 before and after addition of 562+ (0 – 2.5 equiv). (b) Enlarged region from 5.8 - 6.4 ppm of the titration spectra (400 MHz, 298K; [35] = 8.63×10-3 M).  83 mole fraction of macrocycle 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x  m ol e fra ct io n 0.00 .02 .04 .06 .08 .10 .12 .14 .16 .18  Figure 2.19 Job plot of macrocycle 35 with guest 562+ in CDCl3/CD3OD (3:1) (400 MHz, 298 K).  (a) (b) Figure 2.20 The illustration of 2:1 complex (a) and 1:1 complex (b) formed by macrocycle 35 and 562+.  2.2.3.2 Formation of Host-Guest-Guest 3 in 1 Complex  In 1988, the synthesis of cyclobis(paraquat-p-phenylene) (CBPQT4+) 11 was reported by Stoddart’s group.34 It was then discovered that the tetracationic cyclophane had the ability to bind the electron donor tetrathiafulvalene (TTF) 57 within its cavity to form a 1:1 complex.35  84 Since then, CBPQT4+ has been used as an electron accepting host to form host-guest complexes,36 rotaxanes37 and catenanes38. Because of its small volume, it is also a potential guest if the host is a large electron rich macrocycle. The only example of CBPQT4+ functioning as a guest was recently reported by Chen,39 who synthesized a crown-ether-based scaffold to interlock the big guest. The large cavity, cation affinity, and flexibility of these Schiff-base macrocycles inspired us to investigate complexation of CBPQT4+. Because the dimension of CBPQT4+ is 1.03 × 0.68 × 0.42 nm,40 it is too big to fit inside most macrocycles. However, the cavity dimensions of macrocycles 35 and 41 seem adequate to accommodate CBPQT4+. Despite the anticipated size complementarities, 1H NMR spectroscopic experiments showed macrocycles 35 and 41 are poor hosts for CBPQT4+. The reason for the low binding affinity is that including such a big guest, the attractive force between host and guest must not be strong enough to overcome the steric hindrance in these cases. It was thought that increasing the electron density on the host may increase the electrostatic interaction so that the macrocycle would bind CBPQT4+. Macrocycle 46, which contains 10 hydroxyl groups, was designed with this in mind and may be a good candidate for binding CBPQT4+. The 2D-ROESY spectrum of the complex in Figure 2.21 clearly reveals intermolecular contacts that confirm the inclusion of CBPQT4+ inside the cavity of macrocycle 46.   85 N N N N H H H H f e g h HO OH N N N N C5H11O C5H11O OC5H11 OC5H11 OH OH OH HO HO HO N N N N HO OH OC5H11 OC5H11 C5H11O C5H11O Ha Hb Hc Hd i j 14 CBPQT4+ 4346  Figure 2.21 Partial of 2D-ROESY spectrum of the complex formed by macrocycle 43 and CBPQT4+ in 1:1 CDCl3/CD3CN with a mixing time of 120 ms (400 MHz, 298K). Structures are shown beside the spectrum to show proton assignments.  In the 2-D ROESY NMR spectrum (Figure 2.21), the coupling between Hi and Hj was not observed. This suggests the conformation of macrocycle 46 is similar to the alternate cone structure adopted by 41, with the hydroxyl protons Hi and Hj positioned at different ends of the cone structure. From the ROE couplings shown in Figure 2.21, CBPQT4+ is included inside the cavity of macrocycle 46, and it is mobile inside the macrocycle. Spin couplings between host and guest determined from 2D ROESY NMR spectrum are assigned to the conformations depicted in Figure 2.22. These conformations are only snapshots of dynamic guest exchange and motion inside the cavity, and there are many different stable configurations – semi-empirical calculations revealed many stable conformations of the CBPQT4+ cation in the macrocycle, with several  86 different conformations of the macrocycle.  (a) (b) (c) (d)  Figure 2.22 The assignment of spin-couplings and the corresponding conformations. (The guest in structure (a) rotates 90º to give (b) and the guest in (c) rotates 90º to give (d). The alkoxy chains are omitted for clarity.) The structures shown are models that account for the observed ROESY spectrum, not calculated conformations.  The binding constant of CBPQT4+ ⊂ 46 complex was determined by 1H NMR titration experiments to be (1.68 ± 0.53)×104 M-1 and a Job plot (Figure 2.23) shows the stoichiometry of the complex of CBPQT4+ ⊂ 46 is 1:1  87 mole fraction of macrocycle 43 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .02 .04 .06 .08 .10 .12 .14 mole fraction of macrocycle 46  Figure 2.23 Job plot of macrocycle 46 with CBPQT4+ in 1:1 CDCl3/CD3CN (400 MHz, 298 K).  It is known that the electron-deficient CBPQT4+ cation will form a 1:1 inclusion complex with the electron-rich compound, tetrathiafulvalene (TTF)36 and the binding constant is as high as 1×104 M-1 in MeCN.41 This precedent prompted us to investigate the possibility of TTF binding inside the cavity of CBPQT4+ in the complex CBPQT4+ ⊂ 46 forming a host-guest-guest 3-in-1 complex. Figure 2.24 shows the 1H NMR spectra of different combinations of macrocycle 46, CBPQT4+, and TTF. When CBPQT4+ was added into the solution of macrocycle 46, the two hydroxyl proton resonances of macrocycle 46 shifted downfield from 14.46 and 14.34 ppm to 14.75 and 14.66 ppm, respectively. These changes in chemical shift further verified the inclusion of CBPQT4+ inside macrocycle 46.  88 46 46 + CBPQT4+ 46 + CBPQT4+ + TTF CBPQT4+ + TTF 46 + TTF 46 46 + CBPQT4+ 46 + CBPQT4+ + TTF CBPQT4+ + TTF 46 + TTF TTF (a) (b)   Figure 2.24 (a) Partial of 1H NMR spectra of different combinations of macrocycle 46, CBPQT4+ and TTF (400 MHz, acetone-d6, 298K). (b) Enlarged spectral region around 6.6 ppm from (a).  Upon addition of TTF, these two peaks shifted further downfield (8 equiv of TTF were used for a clear observation of the effects of TTF addition) to 14.78 and 14.77 ppm, respectively,  89 revealing an interaction between TTF and the CBPQT 46 complex. No changes in the NMR spectrum of 46 are observed when macrocycle 46 is combined in solution with TTF in the absence of CBPQT , as shown in Figure 2.24b. In this case, there is no complex formation between the electron-rich macrocycle and TTF. When CBPQT  was combined with TTF in solution, the TTF resonance shifted from 6.60 ppm to 6.58 ppm. This small change indicates the formation of a 1:1 complex between CBPQT  and TTF.  When macrocycle 46 was added to the solution of the TTF CBPQT  complex, the TTF resonance shifted further upfield to 6.57 ppm. Meanwhile, as shown in Figure 2.24a, all four resonances of CBPQT  shift upfield with the addition of macrocycle 46 to the TTF CBPQT  complex. These 4+ ⊂ 4+ 4+ 4+ 36 ⊂ 4+ 4+ ⊂ 4+ changes in chemical shift for CBPQT4+ and TTF indicate macrocycle 46 has included both CBPQT4+ and TTF inside its cavity and a new kind of host-guest-guest 3-in-1 complex is formed. The host-guest-guest complex is assembled by electrostatic interaction which exists between macrocycle 46 and CBPQT4+ and also between CBPQT4+ and TTF. To the best of our knowledge, this is the first report of such a non-covalent host-guest-guest complex formed by three organic components. Only two other examples of host-guest-guest structures were found in the literature, but both had only a single ion as the smallest guest, and one was only observed in the solid state.42,43  2D-ROESY NMR spectroscopy (Figure 2.25) also provided evidence for the formation of a host-guest-guest complex. From this spectrum, couplings between Hc and Har, Hd and Hb, Hd and Har show that CBPQT4+ is included inside the macrocycle 46. Spin coupling between Hf and He, Hf and Hc, Hf and Har indicate that TTF is included inside CBPQT4+ and it also interacts with macrocycle 46. Cross-peaks are also observed between TTF and the aryl rings  90 of macrocycle 46, consistent with the 3-in-1 structure. HO OH N Ph N N N OH OH HO HO N N N N HO OH OC5H11 OC5H11 H11C5O H11C5O OC5H11 OC5H11H11C5O H11C5O N N N N S S S S OH HO H HHar ar ar Hb He H H c d H f   c d ef b ar ar c d ar ar b f e (c,f) (c,ar) (c,ar) (d,b) (d,ar) (d,ar) (ar,f) (f,e)  Figure 2.25 Partial of 2D-ROESY spectrum of the complex formed by macrocycle 46, CBPQT4+, and TTF in 1:3 CDCl3/CD3CN with a mixing time of 400 ms (400 MHz, 298K). Labelled structures above the spectrum show proton assignments (The peaks near 7.2 ppm are attributed to the aromatic protons on ketimine phenyl rings. As these peaks were not resolved, “ar” is used to denote them collectively.).  91  MALDI-TOF mass spectrometry supported the formation of the host-guest-guest complex. In the mass spectrum (Figure 2.26), peaks assigned to [46 + CBPQT4+ + TTF + H2O + 3PF6-]+, as well as other species that would be expected, including [CBPQT4+ + 3PF6-]+, and [46 + CBPQT4+ + 3PF6-]+, were observed. Some additional peaks were not assigned, and may be due to complexes with the matrix.  Figure 2.26 MALDI-TOF mass spectrum of the host-guest-guest complex.  The experimental data indicate that CBPQT4+ is mobile inside macrocycle 46. Based on this observation, we simulated the 3-in-1 complex by putting TTF “above” and “below” the  92 macrocycle, subsequently minimizing the energy with MMFF. Figure 2.27 shows the results of our simulations. It is clear that all three components can fit together in the host-guest-guest complex, though the TTF cannot be completely inside the CBPQT4+ while it is inside 46. (a) (b) (c) (d)  Figure 2.27 Energy minimized (MMFF) models of the host-guest-guest complex formed between macrocycle 46, CBPQT4+, and TTF. (a) and (b) show the top and side views of one conformation; (c) and (d) show the top and side views of another. Alkoxy chains and hydrogen atoms are removed for clarity.      93 2.3 Conclusion  This chapter described the synthesis of new rectangular [2+2] Schiff-base macrocycles using combinations of aldimine and ketimine condensation, and demonstrated that Schiff-base macrocycles form host-guest complexes with organic ammonium cations, pyridinium cations, methyl viologen derivatives, and dipyrizinium compounds. The macrocycles are both size and charge selective in terms of guest binding. 2D-ROESY NMR experiments demonstrated that the charged headgroup is situated inside the cavity of the macrocycle. A new macrocycle was prepared that will accommodate the cyclic tetracationic species cyclobis(paraquat-p-phenylene) inside its cavity. This macrocycle was used to assemble a new kind of host-guest-guest 3-in-1 complex formed in solution by a Schiff-base macrocycle, cyclobis(paraquat-p-phenylene), and tetrathiafulvalene. Owing to their flexible backbones and tunable electronic structures, Schiff base macrocycles are promising candidates for selective solution-based cation recognition.  2.4 Experimental  2.4.1 General  Chloroform and acetonitrile were dried over 3 Å molecular sieves. CDCl3 and CD3OD and CD3CN were dried over 3 Å molecular sieves. Dichloromethane as dried by passing it over an activated alumina column. 4,6-Diformylresorcinol 31, 2,3-dihydroxyl-1,4-diformylbenzene 25, 1,3-diformyl-4,5,6-trihydroxylbenzene 4744 and 1,2-dipentyloxyl-4,5-diaminobenzene 4045 were  94 prepared by literature methods. 1H and 13C NMR spectrum were recorded on either a Bruker AV-300 or AV-400 spectrometer. 1H and 13C NMR spectra were calibrated to the residual protonated solvent at δ = 7.24 and 77.00 ppm, respectively in CDCl3. 13C NMR spectra were recorded using a proton decoupled pulse sequence. 2D-ROESY NMR experiments were performed on a Bruker-400 spectrometer. UV-Vis spectra were obtained on a Varian Cary 5000 UV-vis-near-IR spectrophotometer using a 1 cm quartz cuvette. IR spectra were obtained neat in the solid state on a Thermo Nicolet 6700 FT-IR spectrometer. Electrospray ionization (ESI) mass spectra were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. The samples were analyzed in MeOH:CHCl3 (1:1) at 100 μM. Flow rate: 20 μL min-1. MALDI-TOF mass spectra were obtained in a dithranol matrix (cast from THF) on a Bruker Biflex IV instrument where spectra were acquired in the positive reflection mode with delay extraction. Melting points were obtained on a Fisher-John’s melting point apparatus. Molecular structures were simulated with Sparton’04 (Wavefunction, Inc.).  2.4.2 Synthesis and Characterization  Synthesis of 4,6-dihydroxyl-1,3-dibenzoylbenzene 36.20 Under a nitrogen atmosphere, AlCl3 (12 g, 89.8 mmol) was put in a 250 mL Schlenk flask. Dry dichloromethane (DCM) (100mL) was added into the flask with syringe. 1,3-Dimethoxybenzene (5 g, 36.2 mmol) and benzoyl chloride (9 mL, 77.47 mmol) was added into an additional funnel then diluted by 50 mL dry DCM. Under a nitrogen atmosphere, the mixture of 1,3-dimethoxybenzene and benzoyl chloride was added dropwise into the AlCl3 slurry. After stirring for 3 days in room temperature, the  95 yellow solution was poured into 1 M HCl aqueous solution. After stirring for 30 mins, the organic layer was separated with a separation funnel. The aqueous layer was extracted by DCM three times. The combined organic fractions were dried over MgSO4 and solvent removed under vacuum to leave a yellow oil. Methanol was added into the oil and kept in R.T for several hours to afford an off- white solid. Yield 2.5 g (7.9 mmol, 22%).  Data for 4,6-dihydroxyl-1,3-dibenzoylbenzene 36. 1H NMR ( 300 MHz, CDCl3): δ 12.88 (s, 2H), 7.60-7.25 (m, 11H), 6.63 (s, 1H) ppm.  Synthesis of precursor 39. In a Schlenk tube, under nitrogen, 4,6-dihydroxy-1,3-dibenzoylbenzene, 36, (200 mg, 0.63 mmol), and 4,5-diamino-1,2-dipentyloxybenzene (380 mg, 1.4 mmol) were mixed. With a heat gun, the mixture was heated to approximately 210 °C for 5 min until gas evolution was no longer observed from the dark red liquid. After cooling to room temperature, 3 mL MeOH was added into the tube and sonicated for 30 mins. A yellow precipitate formed and was isolated by filtration yielding 117 mg of 39 (0.14 mmol, 22%).  Data for precursor 39. 1H NMR (400 MHz, CDCl3): δ 15.74 (s, 2H), 7.04 (m, 10H), 6.80 (s, 1H), 6.57 (s, 1H), 6.24 (s, 2H), 5.81 (s, 2H), 3.85 (t, 4H), 3.66 (s, 4H), 3.34 (t, 4H), 1.80-0.80 (m, 36H) ppm.13C NMR (100.6 MHz, CDCl3): δ 172.9, 169.0, 149.2, 142.2, 139.3, 135.7, 135.3, 129.8, 129.2, 129.1, 125.7, 114.3, 112.3, 106.0, 103.1, 71.1, 70.1, 29.9, 29.7, 29.1, 29.0, 23.4, 23.3, 15.0 ppm. UV-Vis (CH2Cl2): λmax (ε) = 394 (8.9 x 104), 306 (1.1 x 105), 243 (8.5 x 104) nm  96 (cm-1 mol-1 L). IR (neat) υ = 3465, 3373, 2954, 2930, 2869, 1619, 1568, 1507, 1469, 1331, 1250, 1198, 1113, 988, 918, 846, 698 cm-1. Anal. Calc’d for C52H66N4O6: C 74.08%, N 6.65%, H 7.89%; Found: C 74.06%, N 6.58%, H 7.78%. MALDI-TOF MS (dithranol matrix) m/z = 842.2 [M]+. M.P. = 208–212 °C.  Synthesis of macrocycle 35. In a Schlenk flask, compound 39 (24 mg, 0.03 mmol), compound 25 (4.7 mg, 0.03 mmol), and piperidine (40μL, 0.41 mmol) were dissolved in 60 mL of dry CHCl3:CH3CN (2:1). The flask was fit with a condenser and the reaction mixture was heat to reflux for 16 h under N2. After cooling to room temperature, the solvent was removed under reduced pressure. The remaining solids were suspended in MeOH and filtered yielding a red powder. The crude product was recrystallized from CHCl3/MeOH giving 20 mg of macrocycle 35 (0.01 mmol, 35%).  Data for [2+2] macrocycle 35. 1H NMR (400 MHz, CDCl3): δ 15.20 (s, 4H), 12.89 (s, 4H), 8.35 (s, 4H), 6.95 (m, 26H), 6.61 (s, 4H), 6.52 (s, 2H), 6.14 (s, 4H), 3.91 (t, 8H), 3.57 ( t, 8H), 1.80-0.80 (m, 72H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 173.5, 169.0, 161.5, 150.9, 149.2, 147.8, 139.9, 135.3, 134.3, 129.3, 129.2, 128.8, 122.2, 121.8, 113.7, 110.2, 106.4, 106.3, 77.7, 70.6, 70.0, 29.9, 29.6, 29.1, 29.0, 23.5, 23.4, 15.0 ppm. UV-Vis (CH2Cl2): λmax (ε) = 439 (1.54 x 105), 388 (1.65 x 105), 338 (2.0 x 105), 285 (2.9 x 105) nm (cm-1 mol-1 L). IR (neat) υ = 2952, 2928, 2858, 1615, 1558, 1305, 1259, 1183, 992, 849, 740, 698 cm-1. Anal. Calc’d for C120H136N8O16·2MeOH: C 72.88%, N 5.57%, H 7.22%; Found: C 72.32%, N 5.63%, H 6.88%.  97 MALDI-TOF MS (dithranol matrix) m/z = 1946.4 [M]+. M.P. = 245-250 °C.  Data for 2,3-bis(benzoyloxy)-1,4-dibenzoylbenzene 44.26 1H NMR (300 MHz, CDCl3): δ 7.89 (d, 4H), 7.75 (d, 4H), 7.62 (s, 2H), 7.54 (t, 2H), 7.44 (m, 6H), 7.24 (t, 4H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 193.1, 163.5, 141.8, 136.7, 135.9, 133.6, 133.4, 130.0, 128.5, 128.2, 127.9, 126.9 ppm. UV-Vis (CH2Cl2): λmax (ε) = 239 (3.8 x 104) nm (cm-1 mol-1 L). IR (neat) υ = 1748, 1739, 1660, 1256, 1225, 1084, 1051, 708, 699, 690 cm-1. Anal. Calc’d for C34H22O6: C 77.56%, H 4.21%; Found: C 77.56%, H 4.27%. EI-MS m/z = 526 [M]+. M.P. = 144 °C.  Data for 3,6-dibenzoylcatechol 45. 1H NMR (400 MHz, CDCl3): δ 11.68 (s, 2H), 7.75 (d, 4H), 7.63 (t, 2H), 7.53 (t, 4H), 7.12 (s, 2H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 201.0, 152.6, 137.4, 132.8, 129.5, 128.6, 122.3, 121.3 ppm. UV-Vis (CH2Cl2): λmax (ε) = 405 (2.5 x 103), 301 (2.1 x 104) nm (cm-1 mol-1 L). IR (neat) υ = 1611, 1599, 1417, 1331, 1317, 1299, 1233, 1184, 988, 939, 861, 839, 793, 766, 625, 690 cm-1. Anal. Calc’d for C20H14O4: C 75.46%, H 4.43%; Found: C 75.05%, H 4.48%. EI-MS m/z = 318 [M]+, 241 [M-Ph]+, 212 [M-COPh]+. M.P. = 160 °C.  Synthesis of precursor 42. In a Schlenk flask, 4,5-diamino-1,2-dipentyloxybenzene (500 mg, 1.8 mmol) was dissolved in a mixture of degassed toluene (20 mL) and piperidine (200 μL, 2.0 mmol). Addition of 3,6- dibenzoylcatechol, 45, (282 mg, 0.89 mmol) to the Schlenk flask resulted in the immediate evolution of a deep red color. The solution was heated to reflux for 12 h under N2. Upon cooling to RT, hexanes (80 mL) was added to the reaction flask resulting in  98 the formation of a red precipitate that was isolated by filtration to give 250 mg of 42 (0.30 mmol, 33%).  Data for precursor 42. 1H NMR (400 MHz, CDCl3): δ 15.20 (s, 2H), 7.35 (m, 6H), 7.21 (m, 4H), 6.44 (s, 2H), 6.30 (s, 2H), 5.88 (s, 2H), 3.89 (t, 4H), 3.83 (bs, 4H), 3.37 (t, 4H), 1.77 (m, 4H) 1.51 (m, 4H), 1.39 (m, 8H), 1.28 (m, 8H), 0.91 (m, 12H) ppm.13C NMR (100.6 MHz, CDCl3) δ 171.3, 152.5, 148.9, 141.1, 135.6, 135.0, 129.2, 128.8, 124.8, 121.6, 119.6, 110.8, 102.0, 70.3, 69.3, 29.1, 29.0, 28.4, 28.3, 22.7, 22.6, 14.3, 14.2 ppm. UV-Vis (CH2Cl2): λmax (ε) = 461 (1.7 x 104), 309 (4.0 x 104) nm (cm-1 mol-1 L). IR (neat) υ = 3319, 2954, 2930, 2858, 1608, 1584, 1506, 1465, 1422, 1328, 1261, 1213, 1124, 735, 697 cm-1. Anal. Calc’d for C52H66N4O6: C 74.08%, N 6.65%, H 7.89%; Found: C 74.41%, N 6.76%, H 7.82%. EI-MS m/z = 842 [M]+, 824 [M-H2O]+, 766 [M-Ph]+. M.P. = 173 °C.  Synthesis of macrocycle 41. In a Schlenk flask, compound 42 (56.4 mg, 0.07 mmol), 4,6-diformylresorcinol 31 (11.1 mg, 0.07 mmol), and piperidine (40 μL, 0.41 mmol), were dissolved in 60 mL of dry CH3CN:CHCl3 (1:2). The flask was fit with a condenser and the reaction mixture was refluxed for 16 h under N2. After cooling to room temperature, the solvent was removed under reduced pressure. The remaining solids were suspended in MeOH and filtered yielding a red powder. The crude product was recrystallized from CH2Cl2/MeOH giving 56 mg of macrocycle 41 (0.03 mmol, 41%).  Data for [2+2] macrocycle 41. 1H NMR (400 MHz, CD2Cl2): δ 14.53 (s, 4H), 14.31 (s, 4H),  99 8.57 (s, 4H), 7.49 (s, 2H), 7.20 (m, 20H), 6.80 (s, 4H), 6.54 (s, 2H), 6.45 (s, 4H), 6.19 (s, 4H), 3.95 (t, 8H), 3.68 (t, 8H), 1.90-0.90 (m, 72H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 175.8, 167.1, 158.4, 153.9, 149.4, 147.8, 137.5, 137.2, 135.9, 132.4, 129.7, 128.7, 121.7, 120.8, 114.4, 109.7, 106.1, 104.1, 78.2, 71.2, 70.8, 30.0, 29.8, 29.2, 29.1, 23.5, 23.4, 15.0 ppm. UV-Vis (CH2Cl2): λmax (ε) = 420 (1.68 x 105), 284 (2.8 x 105) nm (cm-1 mol-1 L). IR (neat) υ = 2952, 2928, 2859, 1624, 1604, 1588, 1497, 1330, 1257, 1176, 1155, 849, 700 cm-1. MALDI-TOF MS (dithranol matrix) m/z = 1946.4 [M]+, 1968.5 [M+Na]+. HRMS (ESI) calc’d for 12C11913CH136N8O16: 1946.0108; found: m/z = 1946.0184. M.P. = 270 °C (dec.).  Synthesis of macrocycle 46. Compound 42 (0.150 g, 0.18 mmol) and compound 47 (0.032 g, 0.18 mmol) were dissolved in 100 mL of dry, degassed chloroform and 50 mL of dry, degassed acetonitrile. After the red solution was stirred at room temperature for 5 mins, piperidine (0.04 mL, 0.41 mmol) was added, resulting in a darkening of the solution. The resulting mixture was heated at reflux under nitrogen overnight. After cooling to room temperature, the solution was concentrated to a few mLs by rotary evaporation. Addition of methanol yielded a red precipitate that was isolated by filtration. Recrystallization from chloroform/methanol afforded 46 mg of pure 46 (0.023 mmol, 26%).  Data for macrocycle 46. 1H NMR (400 MHz, CDCl3) : δ 14.53 (s, 4H), 14.39 (s, 4H), 8.31 (s, 4H), 7.11- 7.25 (m, 22H), 6.90 (s, 2H), 6.73 (s, 4H), 6.42 (s, 4H), 6.33 (s, 4H), 3.95 (t, 8H), 3.69 (t, 8H), 0.90-1.98 (m, 88H) ppm. 13C NMR (100.6 MHz, CDCl3) : δ 176.0, 157.9, 154.5, 153.7, 149.5, 148.0, 137.3, 135.9, 134.6, 131.6, 129.8, 129.7, 128.8, 122.0, 121.0, 114.1, 109.7, 103.4,  100 78.2, 70.9, 70.3, 30.0, 29.7, 29.2, 29.1, 23.5, 23.4, 15.0 ppm; IR: υ = 3500, 3055, 2952, 2929, 2859, 1605, 1583, 1494, 1443, 1417, 1379, 1329, 1256, 1209, 1151, 1073, 1039, 984, 920, 889, 854, 803, 774, 701, 573, 463 cm-1; UV-vis (CH2Cl2) : λmax (ε) = 376 (4.96×104), 315 (5.75×104) nm (L mol-1 cm-1); MALDI-TOF: m/z 1979.1 [M+H]+; HRMS (ESI): C120H137N8H18 Calc’d: 1978.0051, Found: 1978.0068. m.p.= 245 °C (dec.).  2.4.4 Simulation of Molecular Structure  The structures of both macrocycles and host-guest complexes were simulated by semi-empirical methods with Sparton’04. The macrocycles were constructed as planar structures first, and energy-minimized structures were obtained from several twisted conformations. Energy-minimized structures were then subjected to PM3 calculation by setting the total charge as neutral for macrocycles and as a +1 cation for host-guest complexes. .          101 2.5 References   1 (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495. (b) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017. 2 (a) Lehn, J.-M. Supramolecular Chemistry; VCH Publishers: New York, 1995. (b) Gloe, K., Macrocyclic Chemistry: Current Trends and Future Perspectives; Springer: Dordrecht, The Netherlands, 2005. (c) Schrader, T.; Hamilton, A. D. Functional Synthetic Receptors; Wiley-VCH: Weinheim, Germany, 2005. 3 (a) Schneider, H.-J. Angew. Chem. Int. Ed. 2009, 48, 3924. (b) Brotin, T.; Dutasta, J.-P. Chem. Rev. 2009, 109, 88. (c) Ono, K.; Yoshizawa, M.; Akita, M.; Kato, T.; Tsunobuchi, Y.; Ohkoshi, S.-i.; Fujita, M. J. Am. Chem. Soc. 2009, 131, 2782. (d) Lledo, A.; Restorp, P.; Rebek Jr., J. J. Am. Chem. Soc. 2009, 131, 2440. (e) Gasa, T. B.; Spruell, J. M.; Dichtel, W. R.; Sørensen, T. J.; Philp, D; Stoddart, J. F.; Kuzmic, P . Chem. Eur. J. 2009, 15, 106. (f) Menand, M.; Jabin, I. Org. Lett. 2009, 11, 673. 4 (a) Chambron, J.-C.; Meyer, M. Chem. Soc. Rev. 2009, 38, 1663. (b) Muller, T. Angew. Chem. Int. Ed. 2009, 48, 3740. (c) Li, S. J.; Liu, M.; Zhang, J. Q.; Zheng, B.; Wen, X. H.; Li, N.; Huang, F. H. Eur. J. Org. Chem. 2008, 6128. 5 (a) Isaacs, L. Chem. Commun. 2009, 619. (b) Kim, K.; Selvapalam, N.; Ko, Y. H.; Park, K. M.; Kim, D.; Kim, J. Chem. Soc. Rev. 2007, 36, 267. (c) Hwang, I.; Ziganshina, A. Y.;Ko, Y. H. Yun, G.; Kim, K. Chem. Commun. 2009, 416.  102  6 (a) Homden, D. M.; Redshaw, C. Chem. Rev. 2008, 108, 5086. (b) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713. (c) Maes, W.; Dehaen, W. Chem. Soc. Rev. 2008, 37, 2393. (d) Morohashi, N.; Narumi, F.; Iki, N.; Hattori, T.; Miyano, S. Chem. Rev. 2006, 106, 5291. 7 (a) Harada, A.; Takashima, Y.; Yamaguchi, H. Chem. Soc. Rev. 2009, 38, 875. (b) Villalonga, R.; Cao, R.; Fragoso, A. Chem. Rev. 2007, 107, 3088. (c) D’Souza, V. T.; Lipkowitz, K. B. Chem. Rev. 1998, 98, 1741. (d) Wang, H.; Wang, S.; Su, H.; Chen, K.-J.; Armijo, A. L.; Lin, W.-Y.; Wang, Y.; Sun, J.; Kamei, K.-i.; Czernin, J.; Radu, C. G.; Tseng, H.-R. Angew. Chem. Int. Ed. 2009, 48, 4344. 8 For other recent examples, see: (a) Caltagirone, C.; Gale, P. A. Chem. Soc. Rev. 2009, 38, 520. (b) Katayev, E. A.; Kolesnikovb G. V.; Sessler J. L. Chem. Soc. Rev. 2009, 38, 1572. (c) Wang, M.-X. Chem. Commun. 2008, 4541. (d) Wright, A. T.; Anslyn, E. V. Chem. Soc. Rev. 2006, 35, 14 (e) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97, 1609. 9 Cram, D. J. and Cram, J. M. Science 1974, 183, 803. 10 (a) Dougherty, D. A. Chem. Rev. 2008, 108, 1642. (b) Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303. (c) Chow, C. S.; Bogdan, F. M. Chem. Rev. 1997, 97, 1489. (d) Dougherty, D. A. Science 1996, 271, 163. 11 (a) MacLachlan, M. J. Pure Appl. Chem. 2006, 78, 873. (b) Borisova, N. E.; Reshetova, M. D.; Ustynyuk, Y. A. Chem. Rev. 2007, 107, 46. (c) Vigato, P. A.; Tamburini, S.; Bertolo, L. Coord. Chem. Rev. 2007, 251, 1311. (d) Brooker, S. Eur. J. Inorg. Chem. 2002, 2535. 12 (a) Korich, A. L.; Hughes, T. S. Org. Lett. 2008, 10, 5405. (b) Ziach, K.; Jurczak, J. Org. Lett. 2008, 10, 5159. (c) Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahedron Lett. 2001, 42, 8861. (d)  103  Arbaoui, A.; Redshaw, C.; Hughes, D. L. Chem. Commun. 2008, 4717. (e) Boden, B. N.; Hui, J. K.-H.; MacLachlan, M. J. J. Org. Chem. 2008, 73, 8069. (f) Saggiomo, V.; Lüning, U. Eur. J. Org. Chem. 2008, 4329. (g) Boden, B. N.; Abdolmaleki, A.; Ma C. T.-Z.; MacLachlan M. J. Can. J. Chem. 2008, 86, 50. (h) Hodacova, J.; Budesinsky, M. Org. Lett. 2007, 9, 5641. (i) Hui, J. K.-H.; MacLachlan, M. J. Chem. Commun. 2006, 2480. (j) Ma, C. T.-Z.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2005, 44, 4178. (k) Gallant, A. J.; Yun, M.; Sauer, M.; Yeung, C. S.; MacLachlan, M. J. Org. Lett. 2005, 7, 4827. (l) Gallant, A. J.; MacLachlan, M. J. Angew. Chem. Int. Ed., 2003, 42, 5307. 13 (a) Ray, A; Pilet, G; Gómez-García, C. J.; Mitra, S. Polyhedron 2009, 28, 511 (b) Moroz, Y. S.; Kulon, K; Haukka, M; Gumienna-Kontecka, E; Kozłowski, H; Meyer, F.; Fritsky, I. O. Inorg. Chem. 2008, 47, 5656. 14 (a) Gupta K. C.; Sutar, A. K. Coord. Chem. Rev. 2008, 252, 1420. (b) Anbu, S.; Kandaswamy, M.;  Suthakaran, P.; Murugan, V.; Varghese, B. J. Inorg. Biochem. 2009, 103, 401. (c) Martinez, A.; Hemmert, C.; Loup, C.; Barre, G.; Meunier, B. J. Org. Chem. 2006, 71, 1449. 15 (a) Hoger, S. Chem. Eur. J. 2004, 10, 1320. (b) Sessler, J. L.; Melfi, P. J.; Tomat, E.; Callaway, W.; Huggins, M. T.; Gordon, P. L.; Keogh, D. W.; Date, R. W.; Bruce, D. W.; Donnio, B. J. Alloys Compd. 2005, 418, 171. (c) Sessler, J. L.; Melfi, P. J.; Pantos, G. D. Coord. Chem. Rev. 2006, 250, 816. 16 (a) Katayev, E. A.; Boev, N. V.; Myshkovskaya, E.; Khrustalev, V. N.; Ustynyuk, Y. A. Chem. Eur. J. 2008, 14, 9065. (b) Katsiaouni, S.; Dechert, S.; Brinas, R. P.; Bruckner, C.; Meyer, F. Chem. Eur. J. 2008, 14, 4823.  104  17  Barba, V.; Villamil, R.; Luna, R.; Godoy-Alcantar, C.; Hopfl, H.; Beltran, H. I.; Zamudio-Rivera, L. S.; Santillan, R.; Farfan, N. Inorg. Chem. 2006, 45, 2553. 18 Gallant, A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2003, 42, 5307. 19 Hui, J. K.-H.; MacLachlan M. J. Chem. Commun. 2006, 2480. 20 Abdul-Aziz M.; Auping, J. V.; Meador, M. A., J. Org. Chem., 1995, 60, 1303. 21 Atkins, R.; Brewer, G.; Kokot, E.; Mockler, G. M.; Sinn, E. Inorg. Chem. 1985, 24, 127. 22 Gerhards, M; Unterberg, C.; Schumm, S. J. Chem. Phys. 1999, 111, 7966. 23 Dalla Cort, A.; Mandolini, L.; Palmieri, G.; Pasquini, C.; Schiaffino, L. Chem. Commun. 2003, 2178. 24 Gallant, A. J.; MacLachlan, M. J. Angew. Chem. Int. Ed. 2003, 42, 5307. 25 (a) Dischendorfer, O.; Limontschew, W. Monatsh. Chem. 1949, 80,741. (b) Limontschew, W.; Wiesenberger, E. Monatsh. Chem. 1952,83, 137. 26 The values of diameters of these macrocycles show considerable variability from in the literature. This variation likely arises from the use of different methods for diameter measurement, but the methods are generally not specified. 27 Kim, K.; Selvapalam, N.; Oh, D. H. J. Inclusion Phenom. Macrocyclic Chem. 2004, 50, 31. 28 Shanmugam, M.; Ramesh, D.; Nagalakshmi, V.; Kavitha, R.; Rajamohan, R.; Stalin, T. Spectrochim. Acta Part A. 2008, 71, 125. 29 Shinkai, S; Araki, K.; Manabe, O. Chem. Commun. 1988, 187. 30 Macomber, R. S. J. Chem. Ed. 1992, 69, 375. 31 Ong, W.; Kaifer, M. G.; Kaifer, A. E. Org. Lett. 2002, 4, 1791.  105  32 Jacques, A. D. S.; Wyman, I. W.; Macartney, D. H. Chem. Commun. 2008, 4936. 33 (a) Marcus, Y.; Hefter, G. Chem. Rev. 2006, 106, 4585. (b) Roelens, S.; Vacca, A.; Venturi, C. Chem. Eur. J. 2009, 15, 2635. (c) Wintergerst, M. P.; Levitskaia, T. G.; Moyer, B. A.; Sessler, J. L.; Delmau, L. H. J. Am. Chem. Soc. 2008, 130, 4129. (c) Gale, P. A. Chem. Commun. 2005, 3761. 34 Odell, B.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D. J. Angew. Chem. Int. Ed. Engl. 1988, 27, 1547. 35 Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1991, 1584. 36 Nielsen, M. B.; Jeppesen, J. O.; Lau, J.; Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J. Org. Chem. 2001, 66, 3559. 37 Yoon, I.; Miljanic, O. S.; Benitez, D.; Khan, S. I.; Stoddart, J. F. Chem. Commun. 2008, 4561. 38 Collier, C. P.; Mattersteig, G.; Wong, E. W.; Luo, Y; Beverly, K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000, 289, 1172. 39 Cao, J; Jiang, Y; Zhao, J. M.; Chen, C. F. Chem. Commun. 2009, 1987. 40 1.03 × 0.68 nm was reported in the literature (see reference 37) and 0.42 nm is the distance between the two meta-protons of bipyridyl. 41 Nielsen, M. B.; Jeppesen, J. O.; Lau, J.; Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J. Org. Chem. 2001, 66, 3559. 42 Dalgarno, S. J.; Fisher, J.; Raston, C. L. Chem. Eur. J. 2006, 12, 2772. 43 Day, A.; Blanch, R. J.; Arnold, A. P.; Lorenzo, S.; Lewis, G. R.; Dance, I. Angew. Chem. Int.  106  Ed. 2002, 275. 44 Henning, G.; Juergen, H.; Hauptlab, W.; Leverkusen, B. A.-G. Justus Liebigs Ann. Chem., 1978, 2, 345. 45 Antonisse, M. M. G.; Snellink-Ruel, B. H. M.; Yigit, I; Engbersen, J. F. J.; Reinhoudt, D. N. J. Org. Chem. 1997, 62, 9034.   107 Chapter 3  Covalently-linked Molecular Isosceles Triangles*  3.1 Introduction  Elegant control of the architectures of molecules and their self-assembly properties plays a central role in modern chemistry.1 The design and synthesis of discrete molecular polygons and polyhedrons have been under significant development for more than a decade.2 Most of these well-defined structures, such as molecular triangles, squares, tetrahedra, cubes and octahedra, were assembled by metal coordination chemistry.3 Among these structures, the triangle is the simplest one, but only a few examples of such triangles were reported due to lack of 60º angular building blocks.4 Some metal coordinated molecular triangles were shown to be supramolecular hosts and examples of anion binding have been reported.5 Covalent linkage is another method to build molecular triangles.6 The advantage of using covalent methods rather than metal-coordination bonding is the enhanced stability and structural versatility. However, the synthesis of large, covalently-linked triangles is still challenging due to the difficulty of precisely designing and synthesizing regularly shaped molecules. Among the molecular triangles that have been synthesized, most papers reported the synthesis of macrocycles with equilateral triangle shapes; less symmetrical macrocycles  * A version of this chapter has been published: Jiang, J.; MacLachlan, M. J. “Unsymmetrical triangular Schiff base Macrocycles with cone conformations”, Org. Lett. 2010, 12, 1020.  108 with isosceles triangle shapes have been seldom reported. In this chapter, the synthesis and studies of Schiff base macrocycles with isosceles triangular shapes (as shown in Figure 3.1) are described.  HO OH N N N N OH OH HO HO N N H11C5O H11C5O OC5H11 OC5H11 C12H25O OC12H25 53 HO OH N N NH HN H25C12O H25C12O OC12H25 OC12H25 O O O O NH HN OC12H25H25C12O 5458 59 Figure 3.1 Structure of molecular isosceles triangles 58 and 59.  3.2 Results and Discussion  3.2.1 Synthesis and Characterization of Isosceles Triangle 58  Schiff-base molecular isosceles triangle 58 was first formed as an unexpected product in a careless experiment. On one occasion, in order to synthesize macrocycle 35 from the reaction of 39 with 25 (needed in a 1:1 ratio), compound 39 that contained a bit of diamine was used to react with 25. The 1H NMR spectrum of the product showed there was a major impurity along with 35. With the help of MALDI-TOF mass spectrometry, the impurity was identified as a new isosceles  109 triangle-shaped Schiff-base macrocycle. Subsequently, the macrocycle was synthesized intentionally. Macrocycle 58 was synthesized in two steps, shown in Scheme 3.1 Scheme 3.1 Synthesis of molecular isosceles triangle 58.  HO OH N N NH2NH2 H11C5O H11C5O OC5H11 OC5H11 + OH OH O O CHCl3 / MeCN R.T. overnight 2 HO OH N N NN H11C5O H11C5O OC5H11 OC5H11 OH OH HO HO O O H2N NH2 C12H25O OC12H25 piperidine CHCl3 / MeCN reflux overnight HO OH N N N N OH OH HO HO N N H11C5O H11C5O OC5H11 OC5H11 C12H25O OC12H25 39 25 60 61 58  The molecular structure of 58 seems unusual because it is not flat. The simulation of this molecule with Spartan’04 is shown in Figure 3.2. From the modelling, macrocycle 58 possesses an unsymmetrical triangle-shaped cone structure in which the resorcinol moieties can be regarded as the base of the triangle, the two catechol parts are sides and three diamines moieties are vertices.  110 (b) (c) (a)(a) (b) (c)  Figure 3.2 Energy minimized (PM3) structure of 58 (a) top space-filling view; (b,c) side views. (The alkoxy chains of the macrocycle are not shown as they were not included in the calculation.)  The 1H NMR spectrum of macrocycle 58 is shown in Figure 3.3. Most of peaks were assigned based on a 2D-ROESY spectrum (Figure 3.4). However, we could not (and there was no need to) assign all of the phenyl peaks between 6.80 and 7.00 ppm because the resolution of the NMR spectrum is too low.   111 *3.73.83.94.04.1 a bc e d h f1 f2 g1 g2 HO OH N N N N OH OH HO HO N N H11C5O H11C5O OCHC4H9 OCHC4H9 C12H25O OCHC11H23 a b c H H d e H H f g Hh Hf HO OH N N N N OH OH HO HO N N H11C5O H11C5O OCHC4H9 OC 4 9 C12H25O OCHC11H23 a b c H H d e H H f g Hh Hf H h b h f1 f2 3.73.83.94.04.1 f1 f2 g1 g2  Figure 3.3 1H NMR spectrum of macrocycle 58 (400 MHz, CDCl3, 298K).  Peak a is attributed to the hydroxyl proton on the resorcinol moiety (Ha) by comparison with where it is found in precursor 39. Peaks b and c are attributed to two catechol-based hydroxyl resonances. The detailed assignment of these two peaks is based on 2D-ROESY  NMR spectrum (Figure 3.4a). From Figure 3.4a, an exchange signal is only present between a and c, but ROE crossing is observed between a and b, indicating that peak b corresponds to the hydroxyl proton (Hb) that is closer to Ha in space. The peaks at 8.64 and 8.57 ppm are assigned to imine resonances. From Figure 3.4b, there are spin coupling between peaks e and c, and d and b. Therefore, peaks e and d are attributed to He and Hd, respectively. The peaks g1 and g2 are resonances of Hg. The reason why this resonance is separated into two peaks will be discussed later. 2D-ROESY NMR spectrum (Figure 3.4c) shows that both g1 and g2 shown spin coupling  112 with peak h, which indicates that peak h is attributed to the resonance of the phenyl proton that is close to Hg. From integrations of peak f1 and peak f2, they are signals of –OCH2- on the –OC5H11 chains. There are two chemically distinct –OC5H11 chains on the macrocycle, so the two resonances are expected. Based on the available data, it is still difficult to conclusively assign peaks f1 and f2 (i.e., which one is closer to the resorcinol and which is closer to the catechol).  a b c a b c e d b c (a) (b) g1 g2 h (c) Figure 3.4 (a) Partial 2D-ROESY spectrum of macrocycle 58 from 12.5 to 15.3 ppm (F1) and from 12.5 to 15.3 ppm (F2) (b) Partial 2D-ROESY spectrum of macrocycle 58 from 13.4 to 13.8 ppm (F1) and from 8.5 to 8.7 ppm (F2) (c) Partial 2D-ROESY spectrum of macrocycle 58 from  113 5.7 to 6.6 ppm (F1) and from 3.2 to 4.4 ppm (F2) (The peak assignment of these ROESY spectra are based on the structure in Figure 3.3; All three graphics are from the same 2D-ROESY spectrum, but with different intensity scaling.) (400 MHz, CDCl3, 298 K).  The isosceles triangle-shaped macrocycle has three N2O2 pockets, one flanked by two imines and the other two by one ketimine and one aldimine. The symmetry of the N2O2 pockets that incorporate a ketimine and an aldimine is low, which may be useful for developing chirality in metal complexes. The 1H NMR spectrum of 58 showed two distinct resonances for the OCH2 (Hg1 and Hg2 in Fig. 3.5b) of the OC12H25 chain. The peaks, g1 and g2, are located at 3.83 and 3.73 ppm, respectively (shown in Fig. 3.3). A 1H-1H COSY NMR spectrum confirmed that peaks g1 and g2 couple with each other (Fig. 3.5a) and are assigned to these two protons. In 58, these two protons are therefore diastereotopic, indicating that there is no plane of symmetry that interchanges them – the macrocycle is not planar. Upon heating, these peaks coalesce, indicating that the macrocycle is interconverting between cone conformations (Figure 3.6) on the NMR timescale. The observation of a stationary conformation at room temperature in these Schiff base macrocycles is interesting and potentially important for generating chiral cycles and other supramolecular structures.    114 (a) (b) g1 g2 OO N N H H23C11 H HO HO OH OH H H23C11 H g1 g2 g1 g2   Figure 3.5 Partial 2D 1H-1H COSY NMR spectrum of 58 from 3.5 ppm to 4.2 ppm for F1 and from 3.5 ppm to 4.3 ppm for F2 (400 MHz, CDCl3, 298 K). (c) The structure that leads to diastereotopic protons Hg1 and Hg2.  Semi-emperical calculation (PM3) shows macrocycle 58 exhibits different conformations. The energies of these conformations are very close to each other. Representative conformations are shown in Figure 3.6.    115 (a) (b) (c) E = 158 kal / mol E = 158 kcal / mol E = 158 kcal / mol Figure 3.6 Representative energy-minimized conformations of macrocycle 58 as deduced by semi-empirical (PM3) calculations. The energy of the conformation is shown beneath each structure.  3.2.2 Synthesis and Characterization of Isosceles Triangular Macrocycle 59.  By a similar strategy to the synthesis of macrocycle 58, a naphthalene-incorporating molecular isosceles triangle 59 was synthesized as shown in Scheme 3.2.        116 Scheme 3.2 Synthesis of macrocycle 59. HO OH N N NH2 NH2 H25C12O H25C12O OC12H25 OC12H25 + OH OH O O CHCl3 / MeCN 2 R.T. HO OH N N N N H25C12O H25C12O OC12H25 OC12H25 OH OH HO HO O O H2N NH2 C12H25O OC12H25 Piperidine CHCl3 / MeCN R.T. for 0.5h, then reflux overnight HO OH N N N N H25C12O H25C12O OC12H25 OC12H25 OH OH HO HO N N OC12H25H25C12O HO OH N N NH HN H25C12O H25C12O OC12H25 OC12H25 O O O O NH HN OC12H25H25C12O 62 28 63 61 6459  In the 1H NMR spectrum of 59 (Figure 3.7a), the OH resonances (a, b, e in Fig. 3.7a) appear as two doublets and a singlet. 1H-1H COSY NMR spectroscopy (Figure 3.7b) revealed that the doublets near 15 ppm arise from coupling to the imine protons near 9 ppm. As this coupling is only observed in the keto-enamine form and not the enol-imine form of salicylaldimines,7 macrocycle 59 is predominantly the keto-enamine form rather than the enol-imine form 64. Tautomerization of naphthalenediimines is known,8 and it is also known that tautomerization of resorcinoldiimines is too high in energy. 9  Our group has previously observed keto-enol tautomerism in a Schiff base macrocycle. Macrocycle 59 is the first to have both keto-enamine and enol-imine tautomers in the same cycle.  117 ppm a b c d f g e (a)  (b)  Figure 3.7 (a) 1H NMR spectrum of macrocycle 59 (400 MHz, CDCl3, 298 K). (b) 2D 1H-1H COSY NMR spectrum of macrocycle 59 (400 MHz, CDCl3, 298 K).  To explore the possibility that the tautomerization of the macrocycle, as observed in 59, affects the kinetics of cone inversion, VT-NMR studies of both 58 and 59 at high temperature were conducted (VT-NMR spectrum of 59 is shown in Figure 3.8). Qualitatively, macrocycle 59  118 with naphthalene rings shows a higher barrier to inversion (coalescence of the methylene OCH2C11H23 protons at 65 ºC) than 58 (55 ºC). The dynamic NMR lineshapes at high temperature were fit using TopSpin 2.1.   Figure 3.8 Partial 1H VT-NMR spectrum of macrocycle 59 (From 3.4 to 4.4 ppm) (400 MHz, 1,1,2,2-tetrachloroethane-d2).  Table 3.1 Kinetic parameters for the macrocycle 58 and 59. Ea ΔH≠ ΔS≠ kJ mol-1 ln A kJ mol-1 J K-1 mol-1 macrocycle 58 109.5±3.8 44.8±1.4 107.0±3.8 118.8±12.1 macrocycle 59 146.6±12.6 57.2±4.8 143.3±12.6 190.4±40.2  From the lineshape analysis, the inversion barrier for macrocycle 59 is ca. 37 kJ mol-1 higher than that of macrocycle 58, Table 3.1. Molecular modeling in Spartan suggests that inversion of macrocycle 59 will change the orientation of the N–H bond. The intramolecular N–H…O=C hydrogen bonding is expected to reduce the mobility of the naphthalene-containing rings.  119  3.2.3 Host-Guest Chemistry of Macrocycles 58 and 59  Similar to rectangular [2+2] Schiff-base macrocycles 35, 41 and 46, macrocycles 58 and 59 with isosceles triangle shapes are supramolecular hosts for organic cations. With the addition of cetylpyridinium chloride to macrocycles 58 and 59, peak shifts can be observed in the 1H NMR spectrum (Figure 3.9).  (1) * (a) (b) (c) (a) (i) (ii) (iii)     120 (a) (b) (c) * (2) (b) (i) (ii) (iii)   Figure 3.9 (a) (i) Partial 1H NMR spectrum of macrocycle 58 from 5.0 to 15.0 ppm. (400 MHz, CD2Cl2, 298 K) (ii) Partial 1H NMR spectrum of mixture of cetylpyridinium chloride 48+Cl- and macrocycle 58 (400 MHz, CD2Cl2, 298 K, [48+]:[58] = 3:1) (iii) 1H NMR spectrum of pyridinium chloride 48+Cl- (400 MHz, CD2Cl2, 298 K). (b) (i) 1H NMR spectrum of macrocycle 58 (400 MHz, CDCl3, 298 K) (ii) 1H NMR spectrum of mixture of cetylpyridinium chloride 48+Cl- and macrocycle 59 (400 MHz, CDCl3, 298 K, [48+]:[59] = 5:1) (iii) 1H NMR spectrum of pyridinium chloride 48+Cl- (400 MHz, CDCl3, 298 K).  The 2D-ROESY NMR spectrum gave direct evidence that cetylpyridinium 48+ was included inside the cavity of the macrocycles (Figure 3.10).      121  HO OH N N N N OH OH HO HO N N H11C5O H11C5O OC5H11 OC5H11 C12H25O OC12H25 Ha H H b c H H H N HC C15H31 H Ar Ar Ar eH g H f  Ar b,c Ar a f e g  Figure 3.10 2D-ROESY NMR spectrum of the complex formed by macrocycle 58 and cetylpyridinium chloride 48+Cl- with a mixing time of 120 ms (400 MHz, CD2Cl2, 298 K).  Several spin-spin couplings between protons on macrocycle 58 and cetylpyridinium chloride 48+Cl- were observed, including couplings between Hg and Hb or Hc, He and HAr, Hf and HAr, and  122 He and Ha. These couplings prove that cetylpyridinium is included in the macrocycle and indicate that the guest is orientated with respect to the catechol or resorcinol groups (Figure 3.11).  (a) E = 8 kcal / mol (b) E = 14 k cal / mol  Figure 3.11 Computer model of the complex with one of conformations of macrocycle 58 and the assignment of spin-spin coupling from 2D-ROESY NMR spectrum. (a) guest oriented “up” (b) guest oriented “down”.  The formation of a host-guest complex by macrocycle 58 and cetylpyridinium was further verified by MALDI-TOF mass spectrometry as shown in Figure 3.12a. From the mass spectrum, the stoichiometry of the complex is 1:1, which was also proved by a Job plot (Figure 3.12b).  123 1581.8  ([3+H+]+) 1604.1 ( [3+Na+]+) 1620.3 ([3+K+]+) 1860.9 ([3+matrix]+) 1844.7 ([3+matrix-O]+) 1885.1 ([3+6+]+) 58+H+]+) [58+Na ]+) ( 58+K+]+) ([58+matrix+K+]+) [58+matrix+MeOH+Na+]+) ([58+48+]+) (a)  mole fraction of 11+Cl- 0.0 .2 .4 .6 .8 1.0 Δδ  x  m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 mole fraction of 10+Cl-mole fraction of 48+Cl- (b)  Figure 3.12 (a) MALDI-TOF mass spectrum of complex 48+⊂58 (dithranol as matrix). (b) Job plot of macrocycle 58 with cetylpyridinium chloride 48+·Cl- in CDCl3 (400 MHz, CDCl3, 298 K).  124  To better understand the complexing capabilities of macrocycles 58 and 59, I studied the binding properties of other related molecules that could be potential guests, including cetyltrimethylammonium bromide (49+·Br-), tetraethylammonium bromide (65+·Br-) and tetrabutylammonium bromide (50+·Br-).  Table 3.2 Binding constant (Kassoc) of the complexes formed by association of macrocycles and guests at 300 K in CDCl3. guest 48+ guest 49+ guest 65+ guest 50+ Kassoc ( M-1) Kassoc ( M-1) Kassoc ( M-1) Kassoc ( M-1) macrocycle 58 macrocycle 59 1.94±0.59×104 6.32±0.81×103 2.95±0.18×103 7.58±0.72×102 4.20±0.09×102 - [a] 5.00±0.90×101 - [a] [a] Binding constant was estimated to be less than 30 M-1 and difficult to determine by NMR spectroscopy.  PPh4Br, which is too large to fit in the macrocycles, and neutral molecules tested cannot be included inside the macrocycles. From Table 3.2, there are a few interesting conclusions to draw from the binding studies. First, the binding constants are largest for 48+Cl-, which has a pyridyl ring, indicating that π-π interactions probably play a role in stabilizing the host-guest complexes. Secondly, the binding constants for macrocycle 58 are about four times larger than for macrocycle 59, and the binding of two of the guests to macrocycle 59 could not be measured. Although macrocylce 59 has more aromatic rings to potentially interact with the guest, interactions between 59 and guests are smaller than that of 58. This difference is attributed to the  125 keto-enamine tautomerization of the naphthalenediimine moieties, which should render the carbonyl groups as less electronegative than the hydroxyl groups in 58, and thus less able to have strong electrostatic interactions with a cationic guest.  3.3 Conclusions  A simple synthesis of novel isosceles triangle-shaped Schiff base macrocycles has been developed. These Schiff base macrocycles adopt cone-shaped conformations at low temperature, but can rapidly interconvert at higher temperature. Differences in the inversion rate and the guest-binding properties of these new cycles indicate that the keto-enol tautomerization plays a role in modifying the properties of these macrocycles.  3.4 Experimental  3.4.1 General  Chloroform, acetonitrile, CDCl3, CD3OD and CD3CN were dried over 3 Å molecular sieves. 2,3-dihydroxy-1,4-diformylbenzene 25, 2,3-dihydroxy-1,4-diformylnaphthalene 28, 1,2-dipentyloxy-4,5-diaminobenzene, and 1,2-didodecyloxy-4,5-diaminobenzene were prepared by literature methods. 1H and 13C NMR spectrum were recorded on either a Bruker AV-300 or AV-400 spectrometer. 1H and 13C NMR spectra were calibrated to the residual protonated solvent at δ = 7.24 and 77.00 ppm, respectively, in CDCl3 and δ = 5.32 (DCM-d2) and 53.8  126 (DCM-d2). 13C NMR spectra were recorded using a proton decoupled pulse sequence. 2D ROESY NMR experiments were performed on a Bruker 400 MHz spectrometer. UV-Vis spectra were obtained on a Varian Cary 5000 UV-Vis-near-IR spectrophotometer using a 1 cm quartz cuvette. IR spectra were obtained as neat in the solid state on a Thermo Nicolet 6700 FT-IR spectrometer. Electrospray ionization (ESI) mass spectra were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. The samples were analyzed in MeOH:CHCl3 (1:1) at 100 μM. MALDI-TOF mass spectra were obtained in a dithranol matrix (cast from THF) on a Bruker Biflex IV instrument where spectra were acquired in the positive reflection mode with delay extraction. Melting points were obtained on a Fisher-John’s melting point apparatus.  3.4.2 Synthesis and Characterization  Synthesis of 60. Compound 39 (0.152 g, 0.18 mmol) and 3,6-diformylcatechol 25 (0.060 g, 0.36 mmol) were mixed together in a 250 mL RB flask. Dry chloroform (100 mL) and  dry MeCN (50 mL) were added into the flask to give a red solution. The solution was stirred overnight at room temperature under nitrogen. The solvent was removed under vacuum at 30 °C to obtain a red glassy solid. (Rotary evaporation at higher temperature leads to decomposition.) Addition of methanol and sonication yielded a red precipitate that was isolated by filtration. 0.071 g (0.063 mmol, 35%) red solid was obtained.  Data for 60. 1H NMR (CDCl3): δ 14.87 (s, 2H), 13.57 (s, 2H), 10.41 (s, 2H), 10.01 (s, 2H), 8.40  127 (s, 2H), 7.14-6.85 (m, 14H ), 6.78 (s, 1H), 6.64 (s, 2H), 6.61 (s, 1H), 6.18 (s, 2H), 3.91 (t, 4H), 3.68 (t, 4H), 1.78-0.88 (m, 36H) ppm. 13C NMR (CDCl3): δ 195.62, 173.82, 168.11, 158.99, 151.06, 150.68, 149.42, 147.08, 139.46, 135.81, 134.37, 131.84, 128.74, 128.36, 127.95, 123.30, 121.81, 121.52, 121.04, 113.05, 109.07, 105.46, 104.49, 77.43, 70.03, 69.36, 29.17, 28.80, 28.38, 28.28, 22.66, 22.59, 14.23 ppm. IR: υ = 3500, 3055, 2952, 2929, 2858, 1660, 1607, 1567, 1556, 1464, 1392, 1367, 1295, 1257, 1208, 1178, 1129, 984, 918, 849, 780, 737, 697, 595, 539 cm-1. UV-Vis (CH2Cl2): λmax (ε) = 394 (8.0×103), 338 (7.9×103), 286 (1.5×104) nm (cm-1 mol-1 L). ESI-MS: m/z 1161.5 [M+Na]+. HRMS (ESI): C68H75N4O12 Calc’d: 1139.5381, Found: 1139.5393.  Synthesis of macrocycle 58. Under a nitrogen atmosphere, 4,5-didodecyloxy-1,2-phenylenediamine (0.054 g, 0.11 mmol) was dissolved in 150 mL of 2:1 degassed CHCl3:MeCN. Compound 60 (0.128 g, 0.11 mmol) was added, turning the solution from colorless to red. After stirring at room temperature for 1 h, piperidine (0.04 mL, 0.41 mmol) was added. The red solution was further stirred for 12 h at room temperature then solvent was removed by rotary evaporation. Addition of methanol yielded a red precipitate that was isolated by filtration. The crude product was recrystallied from chloroform/methanol and then filtrated. The solvent was removed from the filtrate under vacuum to obtain 0.026 g of pure 58 ( 0.023 mmol, 21%).  Data for macrocycle 58. 1H NMR (CD2Cl2): δ 14.86 (s, 2H), 13.72 (s, 2H), 13.54 (s, 2H), 8.64 (s, 2H), 8.57 (s, 2H), 7.10-6.76 (m, 18H), 6.74 (s, 1H), 6.70 (s, 1H), 6.24 (s, 2H), 4.09 (m, 4H),  128 3.94 (m, 4H), 3.83 (m, 2H), 3.68 (m, 2H), 1.89-0.87 (m, 82H) ppm. 13C NMR (CDCl3): δ 175.26, 168.73, 161.62, 159.26, 152.15, 151.89, 150.45, 149.93, 147.58, 140.33, 137.59, 136.74, 134.84, 132.43, 129.29, 128.97, 127.99, 121.77, 121.60, 121.43, 121.36, 113.67, 109.50, 106.66, 105.07, 104.27, 70.84, 70.25, 32.94, 32.59, 32.53, 30.71, 30.67, 30.65, 30.43, 30.37, 30.29, 29.93, 27.05, 26.67, 26.58, 23.69, 23.57, 15.10, 14.99 ppm. IR: υ = 3610, 3010, 2921, 2851, 1614, 1581, 1513, 1493, 1466, 1442, 1377, 1300, 1256, 1212, 1187, 1133, 1112, 1003, 961, 914, 846, 779, 722, 698, 606 cm-1. UV-Vis (CH2Cl2): λmax (ε) = 403 (3.8×104 ), 343 (3.1×104 ), 285 (4.0×104) nm (cm-1 mol-1 L). Anal. Calc’d for C102H134N6O12·H2O: C 73.65; N 5.26; H 8.07. Found: C 73.91; N 5.16; H 8.01. MALDI-TOF: m/z = 1581.3 [M+H]+, 1603.4 [M+Na]+, 1619.5 [M+K]+. M. P.= 234-235 °C.  Synthesis of 62. Under N2, a Schlenk tube was charged with 4,6-dibenzoylresorcinol, (100 mg, 0.32 mmol) and 4,5-didodecyloxy-1,2-phenylenediamine, 61, (320 mg, 0.67 mmol) and heated with a heat gun to approximately 210 °C for 5 mins until gas evolution was no longer observed. After cooling to room temperature, EtOH was added into the Schlenk tube and the mixture was sonicated for 30 mins. Suspension of the remaining solid in EtOH followed by filtration gave 110 mg of 62 as a yellow powder (0.09 mmol, 28%).  Data for 62. 1H NMR (400 MHz, CDCl3): δ 15.75 (s, 2H), 7.06 (m, 10H), 6.82 (s, 1H), 6.58 (s, 1H), 6.26 (s, 2H), 5.85 (s, 2H), 3.88 (t, 4H), 3.68 (s, 4H), 3.40 (t, 4H), 1.80-0.80 (m, 92H) ppm; 13C NMR (CDCl3) : δ 171.94, 168.14, 148.39, 141.18, 138.26, 134.74, 134.31, 128.86, 128.46, 128.39, 124.96, 113.36, 111.39, 105.08, 102.34, 77.43, 70.43, 69.40, 32.15, 29.89, 29.86, 29.63,  129 29.57, 29.50, 29.33, 26.10, 22.91, 14.33 ppm; UV-Vis (CH2Cl2) λmax (ε) = 423 (2.1 x 104), 283 (4.3 x 104) nm (cm-1 mol-1 L); IR (neat) υ = 3465, 3373, 2954, 2930, 2869, 1619, 1568, 1507, 1469, 1331, 1250, 1198, 1113, 988, 918, 846, 698 cm-1; ESI-MS: m/z = 1235.8 [M+H]+, 1257.6 [M+Na]+; Anal. Calc’d for C80H122N4O6·2.5 H2O: C 75.01; H 9.99; N 4.37 Found: C 75.02; H 9.90; N 4.43; HRMS (ESI): C80H123N4O6 Calc’d: 1235.9443, Found: 1235.9435; M.P.= 126-128 °C.  Synthesis of macrocycle 59. Compound 62 (0.110 g, 0.09 mmol) and 1,4-diformyl-2,3-dihydroxynaphthalene 28 (0.043 g, 0.20 mmol) were mixed together in a 250 mL RB flask. Dry chloroform (100 mL) and dry MeCN (50 mL) were added to give a red solution. The solution was stirred overnight at room temperature under nitrogen to generate compound 63. Compound 63 was used without further purification. The above solution of 63 was degassed. 4,5-Bis(dodecyloxy)-1,2-phenylenediamine  (0.043 g, 0.09 mmol) was added and the solution was stirred at room temperature for 30 mins. Piperidine (0.04 mL, 0.41 mmol) was added into the flask. The flask was fit with a condenser and the reaction mixture was refluxed overnight under N2. After cooling to room temperature, the solvent was removed under reduced pressure. The remaining solids were suspended in MeOH and filtered yielding a red powder. The crude product was recrystallized from CH2Cl2/MeOH giving 0.037 g of macrocycle 59 (0.018 mmol, 20%).  Data for macrocycle 59. 1H NMR (400 MHz, CDCl3): δ 15.62 (d, 2H), 15.17 (d, 2H), 14.67 (s, 2H), 9.19 (d, 2H), 8.96 (d, 2H), 7.96-6.70 (m, 24H), 6.29 (s, 2H), 4.11 (m, 4H), 3.96 (m, 4H),  130 3.83 (m, 2H), 3.73 (m, 2H), 1.99-0.86 (m, 138H) ppm. 13C NMR (CDCl3) : δ 164.51, 152.78, 150.06, 149.62, 147.05, 141.03, 135.27, 134.03, 131.56, 128.99, 128.59, 128.03, 127.20, 127.10, 127.05, 126.64, 124.71, 124.53, 119.86, 119.60, 113.26, 111.28, 110.95, 109.25, 105.60, 103.73, 102.90, 70.33, 70.30, 69.54, 32.16, 29.93, 29.89, 29.85, 29.70, 29.60, 29.23, 26.32, 26.27, 26.18, 22.93, 14.36 ppm. UV-Vis (CH2Cl2): λmax (ε) = 470 (3.4 x 104), 286 (5.1 x 104). IR (neat) υ = 3585, 3096, 2922, 2850, 1610, 1564, 1505, 1465, 1310, 1258, 1211, 1177, 1131, 1010, 958, 844, 744, 697, 576, 466 cm-1. Anal. Calc’d for C134H186N6O12·4H2O: C 75.03; N 3.92; H 9.12. Found: C 74.98; N 4.10; H 8.96. MALDI-TOF: m/z = 2073.6 [M+H]+. HRMS (ESI): C134H187N6O12 Calc’d: 2072.4207, Found: 2072.4260. M. P.= 135-138 °C.  3.4.3  Simulation of Molecular Structure The structures of both macrocycles and host-guest complexes were simulated by semi-empirical methods with Sparton’04. The macrocycles were constructed as coplanar structures first, and energy-minimized structures were obtained by minimization of several possible conformations. Energy-minimized structures were then subjected to PM3 calculation by setting the total charge as neutral for macrocycles and as cation for host-guest complexes.        131 3.5 References   1 (a) Beletskaya, I.; Tyurin, V. S.; Tsivadze, A. Y.; Guilard, R.; Stern, C. Chem. Rev. 2009, 109, 1659. (b) Hiratani K.; Albrecht, M. Chem. Soc. Rev. 2008, 37, 2413. (c) Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W. Angew. Chem. Int. Ed. 2007, 46, 2366. (d) Hofmeiera, H.; Schubert, U. S. Chem. Soc. Rev. 2004, 33, 373. (e) Leininger, S.; Olenyuk, B.; Stang, P. J. Chem. Rev. 2000, 100, 853. 2 (a) West, K. R.; Ludlow, R. F.; Corbett, P. T.; Besenius, P.; Mansfeld, F. M.; Cormack, P. A. G.; Sherrington, D. C.; Goodman, J. M.; Stuart, M. C. A.; Otto, S. J. Am. Chem. Soc. 2008, 130, 10834. (b) Zhao, S.-B.; Wang, R.-Y.; Wang, S. J. Am. Chem. Soc. 2007, 129, 3092. (c) Kawano, M.; Kobayashi, Y.; Ozeki, T.; Fujita, M. J. Am. Chem. Soc. 2006, 128, 6558.(d) Yoshizawa, M.; Tamura, M.; Fujita, M. Science 2006, 312, 251.(e) Papaefstathiou, G. S.; Hamilton, T. D.; Friscic T; MacGillivray, L. R. Chem. Commun. 2004, 270. (f) Li, J.-R.; Timmons, D. J.; Zhou, H.-C. J. Am. Chem. Soc. 2009, 131, 6368. (g) Chun, H. J. Am. Chem. Soc. 2008, 130, 800 (h) Cairns, A. J.; Perman, J. A.; Wojtas, L.; Kravtsov, V. C.; Alkordi, M. H.; Eddaoudi, M.; Zaworotko, M. J. J. Am. Chem. Soc. 2008, 130, 1560–1561. 3 (a) Eryazici, I.; Moorefield, C. N.; Newkome, G. R. Chem. Rev. 2008, 108, 1834. (b) McMillin, D. R.; Moore, J. J. Coord. Chem. Rev. 2002, 229, 113. (c) Lee, S. J.;. Hupp, J. T. Coord. Chem. Rev. 2006, 250, 1710. (d) Würthner, F.; You C.-C.; Saha-Möller, C. R. Chem. Soc. Rev. 2004, 33, 133. (e) Fujita, M. Chem. Soc. Rev. 1998, 27, 417. (f) Navarro, J. A. R.; Lippert, B. Coord. Chem. Rev. 2001, 222, 219. 4 (a) Derossi, S.; Casanova, M.; Iengo, E.; Zangrando, E.; Stener M.; Alessio, E. Inorg. Chem.  132  2007, 46, 11243. (b) Schnebeck, R.-D.; Randaccio, L.; Zangrando, E.; Lippert, B. Angew.Chem., Int. Ed. 1998, 37, 119. (c) Neels, A.; Stoeckli-Evans, H. Inorg. Chem. 1999, 38, 6164. (d) Schweiger, M.; Russell Seidel, S.; Arif, A. M.; Stang, P. J. Angew.Chem., Int. Ed. 2001, 40, 3467. (e) Bera, J. K.; Angaridis, P.; Cotton, F. A.; Petrukhina, M. A.; Fanwick, P. E.; Walton, R. A. J. Am. Chem. Soc. 2001, 123, 1515. 5 (a) Schnebeck, R.-D.; Freisinger, E.; Glahe, F.; Lippert, B. J. Am. Chem. Soc. 2000, 122, 1381. (b) Qin, Z.; Jennings, M. C.; Puddephatt, R. J. Inorg. Chem. 2002, 41, 3967. (c) Weilandt, T.; Troff, R. W.; Saxell, H.; Rissanen, K.; Schalley, C. A. Inorg. Chem., 2008, 47, 7588. 6 (a) Abrahams, B. F.; Boughton, B. A.; Choy, H.; Clarke, O.; Grannas, M. J.; Price, D. J.; Robson, R. Inorganic Chemistry, 2007, 46, 11243. (b) Bogdan, N.; Condamine, E.; Toupet, L.; Ramondenc, Y.; Bogdan, E.; Grosu, I. J. Org. Chem. 2008, 73, 5831. (c) Yoshida, K.; Kawamura, S.-i.; Morita, T.; Kimura, S. J. Am. Chem. Soc. 2006, 128, 8034. (d) Gallant A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2003, 42, 5307. 7 (a) Chong, J. H.; Sauer, M.; Patrick, B. O.; MacLachlan, M. J. Org. Lett. 2003, 5, 3823. (b) Yelamaggad, C. V.; Achalkumar, A. S.; Rao, D. S. S.; Prasad, S. K. J. Org. Chem. 2007, 72, 8308. 8 Gallant, A. J.; Yun, M.; Sauer, M.; Yeung, C. S.; MacLachlan, M. J. Org. Lett. 2005, 7, 4827. 9 Sauer, M; Yeung, C; Chong, J. H.; Patrick, B. O. and MacLachlan, M. J. J. Org. Chem, 2006, 71, 775.  133 Chapter 4  Naphthalene-based Keto-enol Tautomerized [2+2] Macrocycle*  4.1 Introduction  Macrocycles have long been investigated as hosts for supramolecular chemistry.1 As one would expect, the size and shape of the cavity within these macrocycles influences their host-guest binding properties. Conjugated macrocycles, such as porphyrins and phthalocyanines, have been extended by substituting the pyrrole or benzene rings with polyaromatic components in order to modify their properties.2 Extending the cavities of the macrocycles and incorporating naphthalene moieties into the macrocycle may change the binding affinity or selectivity of macrocyclic hosts.3 NH HN O O O O NH HN NH HN O O RO OR RO RO OR OR 30 59 66 (R = C5H11) 67 (R = C12H25) N N NH HN O O O O HO OH NH HN N N HO OH OR RO OR OR OR OROR RO HO OH N N NH HN H25C12O H25C12O OC12H25 OC12H25 O O O O NH HN OC12H25H25C12O  Figure 4.1 Structures of macrocycles 30, 59, 66 and 67.   *A version of this chapter will be submitted for publication: Jiang, J.; MacLachlan, M. J. “Lyotropic Liquid Crystal Formed by naphthalene-based Schiff-base Macrocycle”  134  Naphthalene-based Schiff-based macrocycles 30 and 59 (Figure 4.1) with keto-enol tautomerized structure have been synthesized, as discussed in Chapters 1 and 3, respectively. Compared to their benzene-base analogues (27 and 58), the electron distribution in 28 and 59 have been altered, and the supramolecular binding ability of 59 has been changed. In order to further investigate the properties of these naphthalene-based Schiff-base macrocycles, two new macrocycles (66 and 67) were synthesized. Like the other Schiff-base macrocycles, 66 and 67 are good supramolecular host for organic cations, such as pyridinium and ammonium derivatives. Moreover, macrocycle 67 with longer alkyl chains can form lyotropic liquid crystals (LLCs) in organic solvents such as chloroform and 1,2-dichloroethane.  4.2 Results and Discussion  4.2.1 Synthesis and Characterization of 66 and 67   The strategy used to synthesize the [2+2] Schiff base macrocycles 66 and 67 is very similar to that used to prepare macrocycle 35. By reaction of precursor 39 and 62 with 1 equivalent of 1,4-diformyl-2,3-dihydroxynaphthalene 28 and catalytic piperidine, macrocycle 66 and 67 were obtained (Scheme 4.1).      135 Scheme 4.1 Synthesis of macrocycles 66 and 67. N N NH2 NH2HO OH OR RO OR OR + OH OH O O Piperidine CHCl3 / MeCN reflux overnight N N N N OH OH HO HO HO OH N N N N HO OH OR RO OR OR OR OROR RO 39 (R = C5H11) 62 (R = C12H25) N N NH HN O O O O HO OH NH HN N N HO OH OR RO OR OR OR OROR RO 66 (R = C5H11) 67 (R = C12H25) 28    The MALDI-TOF mass spectra of both 66 and 67 show the expected protonated products. The 1H NMR spectrum of 66 shows there are two doublets at 14.67 ppm and 8.77 ppm, which are attributed to the NH (Ha in structure 66 in Fig. 4.2a) and imine (Hb, in structure of 66 in Fig. 4.2a) resonances, respectively. The 1H-1H COSY NMR spectrum of 66 shows there is very strong coupling between these two protons (Figure 4.2b). Strong coupling between Ha and Hb indicate the presence of tautomerized structures on the naphthalene part of macrocycle 66. Tautomerization is not expected to be present at the resorcinol parts, which was proved by our previous work.4 Therefore, both hydroxyl and carbonyl groups are exposed in the interior of the macrocycle, which is confirmed by the presence of peaks at both 3300 cm-1 (O-H stretching  136 mode) and 1614 cm-1 (C=O stretching mode) in the IR spectrum. Each salen unit in the macrocycle incorporates one ketimine, one NH group, one hydroxyl group and one carbonyl group. In principle, such an arrangement may generate an unsymmetrical environment for the metal centre if a metal ion was coordinated.  Figure 4.2 (a) 1H NMR spectrum of macrocycle 66. (400 MHz, CDCl3, 320 K). (b) 2D 1H-1H COSY spectrum of macrocycle 66 (400 MHz, CDCl3, 298 K). (b) (a) * (a) N N NH HN O O O O HO OH NH HN N N HO OH OR RO OR OR OR OROR RO a Hb c a b c  137  Like other Schiff-base macrocycles, [2+2] macrocycles 66 and 67 are able to bind organic cations, such as pyridinium and ammonium derivatives to form host-guest complexes. The formation of 1:1 host-guest complexes was proved by NMR titration (Figure 4.3), Job plots, 2D-ROESY NMR studies (Figure 4.4), and MALDI-TOF mass spectrometry.   HO OH N N NH HN H11C5O H11C5O OC5H11 OC5H11 O O O O NH HN N N HO OH H11C5O H11C5O OC5H11 OC5H11 N HC C15H31 H a Hb Hd Hc e 3 4+ HO OH N N NH HN H 1C5O H 1C5O OC5H 1 OC5H11 O O O O NH HN N N HO OH H 1C5O H 1C5O OC5H 1 OC5H11 N HC C15H31 H a Hd Hc e Hb 3 4+ HO OH N N NH HN H11C5O H11C5O OC5H11 OC5H11 O O O O NH HN N N HO O H11C5O H11C5O OC5H11 OC5H11 N HC C15H31 H a Hd Hc e Hb Hf 3 4+   Figure 4.3 Partial 1H NMR spectra of (a) macrocycle 66; (b) mixture of macrocycle 66 and cetylpyridinium chloride 48+·Cl- ([48+]:[66] = 1.2:1); and (c) cetylpyridinium chloride (400 MHz, CDCl3, 298 K). The peaks are assigned as shown in the molecular structures.  138  From the 1H NMR spectra in Figure 4.3, resonance a shifted from 14.79 to 15.18 ppm after 1.2 equivalents of cetylpyridinium chloride were added. Peak b shifted downfield from 6.61 to 5.69 ppm. Two resonances of cetylpyridinium shifted considerably - from 9.55 to 9.70 ppm for proton d and from 5.07 to 4.84 ppm for proton e. These resonance shifts indicate there are interactions between host and guest molecules when they are mixed. The 2D-ROESY NMR spectrum shows spin-spin coupling between macrocycle 66 and cetylpyridinium 48+ (Figure 4.4). H11C5O OC5H11   Figure 4.4 (a) 2D-ROESY NMR spectrum of complex formed by macrocycle 66 and HO OH N N H11C5O OC5H11 NH HN O O O O NH HN N N HO OH H11C5O H11C5O OC5H11 OC5H11 H H N HC C15H31 Ha b c d H  139 cetylpyridinium chloride with a mixing time of 120 ms (400 MHz, CDCl3, 298 K). The circled cross-peaks (Ha and Hc; Hb and Hd) are couplings between macrocycle 66 and cetylpyridinium 48+.  From the resonance coupling between Ha and Hc, Hb and Hd in the ROESY spectrum, it seems the guest molecule prefers an orientation with the alkyl tail of the guest aligned with the four phenyl rings of ketimine, as shown in Figure 4.5.  (a) (b)  Figure 4.5 (a) The proposed preferred conformation of the host-guest complex 48+⊂66. (b) The illustration of the complex 48+⊂66.   In addition to cetylpyridinium chloride 48+Cl-, the binding ability of 1-dodecyl-3-methylpyridinium bromide 68 and cetyltrimethylammonium bromide 49 (shown in Figure 4.6) were also studied. Compared to [2+2] macrocycle 35, four hydroxyl groups are replaced by carbonyl groups on the interior of 66. Because the electronegativity of oxygen in a carbonyl group is smaller than that for a hydroxyl group (2.34 for carbonyl group5 and 2.8 for hydroxyl group6), one might predict that the binding constant of complexes formed by 66 and organic cations would be smaller than those formed by 35. NMR titration results with  140 cetyltrimethylammonium bromide (49+ Br-) into both 35 and 66 verified this, i.e., 49+ binds stronger with 35 than with 66 (Table 4.1). However, comparison of titration results of pyridinium cations into 35 and 66 tells a different story. From Table 4.1, the binding constant for 48+ and 68+ binding to the macrocycles is 2-3 times higher with 66 than with 35. The main difference between 48+, 68+ and 49+ is that there are aromatic structures in 48+ and 68+. Therefore, the higher binding constants of 48+ and 68+ with 66 may be attributed to the stronger π-π interaction. Calculations showed that naphthalene has a higher interaction energy than benzene with cations and aromatic neutral compounds, 7  which is in accordance with the experimental results described here. N C16H33 Cl- N C12H25 Br- N C16H33 Br- 4+ Cl- 5+ Br- 6+ Br- 44+Cl- 63+Br- 45+Br-48+ l 8+Br- 9+Br-  Figure 4.6 Molecules investigated as potential guests for macrocycles 35 and 66  Table 4.1 Binding constant (Kassoc)8 of the complexes formed by association of macrocycles and guests at 300 K in CDCl3.[a] guest 48+   guest 68+ guest 49+ Kassoc ( M-1) Kassoc ( M-1) Kassoc ( M-1) macrocycle 35   1.85±0.37×104 [b] 2.12±0.48×104  3.24±0.41×103 [b] macrocycle 66 4.67±0.71×104 4.34±0.65×104 2.54±0.53×103 [a] The concentration of hosts was kept constant as 6.11×10-4 M during titration. [b] These two binding constants were discussed in Chapter 2.  141  4.2.2 Liquid Crystal Phases Formed by Macrocycles and Host-Guest Complexes  When macrocycle 67 was dissolved in the chloroform or 1,2-dichloroethane, or in a mixture of chloroform and 1,2-dichloroform, a liquid crystal texture could be observed by polarizing optical microscopy (POM). No liquid crystal texture was found for macrocycle 66 itself. However, when cetylpyridinium was added into the solution of macrocycle 66 in chloroform, a texture was observed. The rest of this chapter describes our investigations of this new result.  4.2.2.1 Liquid Crystal Formed by Macrocycle 67  There are many papers on liquid crystals formed by macrocycles.9 Most liquid crystals formed by macrocycles are thermotropic in which macrocycles often assemble into discotic nematic or columnar phases. Lyotropic liquid crystals are formed in solution, and are very common for surfactants in water. On the other hand, lyotropic liquid crystals formed by macrocycles are rarely reported, especially in non-aqueous solvents.10  Metallomesogen 69 (Figure 4.7) was reported to form column phases in pentadecane.10c The columnar phase was assembled by π-π stacking. Compounds 70 and 71 were reported as amphiphilic molecules that can form a lamellar phase.10a, 10b Although there are macrocyclic structures in 70 and 71, these two molecules can be regarded as having rod-like structures with a hydrophilic head at one end and a hydrophobic tail at the other end.  142 N N OC12H25H25C12O H25C12O M X X M N N M X X M C12H25O OC12H25 OC12H25 H25C12O H25C12O OC12H25 OC12H25 OC12H25C12H25O M = Pd, Pt X = OAc, Cl, Br, I, SCN, N3 (a) (b) N N N Br- OC18H37 (c) O O O O OC12H25 11 64 65 66 69 70 71  Figure 4.7 Structures of some macrocycles that can give lyotropic mesophases.  Macrocycle 67 has a very unusual shape in comparison with 70 and 71, adopting a relatively rigid cone-like structure. A molecule with such a shape is rarely reported to form a liquid crystalline phase. Several kinds of textures were observed for macrocycle 67 in different solvents and concentration. In a solution 10 wt% 62 / 90 wt% CHCl3, a Schlieren texture was observed by POM, as shown in Figure 4.8 (a) (b) Isotropic dry film 200μm 100μm  Figure 4.8 (a) Polarized optical micrographs (50×) of 10 wt % 62 / 90 wt % chloroform at room temperature. (b) A closer view of the texture.  143  The Schlieren texture in Figure 4.8(a) shows parallel dark lines connecting the wedge-shaped disclinations. These walls are inversion walls that are perpendicular to the liquid crystal layer. According to Kazanci’s methods, the Schlieren texture is a discotic nematic phase (Nd).11  When the concentration was increased to approximately 20 wt% 62 / 80 wt% CHCl3, a fish-scale-like grid texture was observed, as shown in Figure 4.9. The periodical grid is a focal conic texture. For a lyotropic liquid crystal, focal conic textures have only been observed in a lamellar phase. Therefore, macrocycle 62 is an amphiphilic molecule in CHCl3 and assembles into a lamellar phase. isotropic dry film FCD (a) 200 μm      144 isotropic dry film (b) 200 μm   Figure 4.9 Polarized optical micrographs (50×) of 20 wt% 67 / 80 wt% chloroform at room temperature.  Macrocycle 67 forms a lamellar phase rather than a columnar phase that is generally observed for LCs formed by macrocycles. The reason lies in the structure of the macrocycle. Below the critical micelle concentration (CMC), macrocycle 67 remains isolated in the solution. Because the macrocycle is very flexible, many kinds of different conformations transform freely in the solution in room temperature. However, above CMC, the amphiphilic macrocycle aligns so that all the alky chains are on one side while the polar groups of the macrocycle, the keto and hydroxyl groups, are oriented on the other side. Therefore, this conformation, shown in Figure 4.10, is the most preferable structure of 67 above the CMC. From Figure 4.10, there are four  145 ketimine phenyl rings on 67, which prevent macrocycles from stacking on top of each other to form a columnar phase. There are two tautomerized naphthalene moieties on the macrocycle. The two naphthalene moieties form a 120˚ angle in the conformation which is always found in the molecules of a banana-shape liquid crystal. Whether the 120˚ angle is a necessity for forming the lyotropic liquid crystal is still under investigation.  ketimine phenyl ring Naphthalene moiety 120°  Figure 4.10 Proposed preferred conformation of 67 after CMC. (Simulated by empirical calculation (PM3)).  To determine whether the presence of two naphthalene moieties is a necessity for the formation of liquid crystal in the macrocycles, macrocycle 72, a [2+2] macrocycle without naphthalene, was synthesized. No liquid crystallinity was observed for 72 in CHCl3, DCM, 1,2-dichloroethane, ethanol and methanol.  146 HO OH N N N N H25C12O H25C12O OC12H25 OC12H25 OH OH HO HO N N N N HO OH H25C12O H25C12O OC12H25 OC12H25 6772  Figure 4.11 Structure of macrocycle 72. It appears that the naphthalene moieties are key to giving the LC mesophase. Naphthalene rings prefer to pack with each other by π-π stacking. π-π Stacking between macrocycles via naphthalene moieties could give a bilayer structure with alkyl chains stretched outwards (Figure 4.12). I propose that macrocycle 67 assembles into inverted micelles in chloroform solution, and these can further form a lyotropic nematic phase or lamellar phase as shown in Scheme 4.2. hydrophilic hydrophobic hydrophobic  Figure 4.12 Proposed bilayer structure by macrocycle 67.       147 Scheme 4.2 Proposed scheme of the formation of Nd and lamellar phase. π-π stacking micelle  The formation of a lamellar phase was verified by the texture of macrocycle 67 in 1,2-dichloroethane (DCE). A typical oily streak texture was observed under POM in a solution of 5 wt% 67 / 95 wt% DCE (Figure 4.13(a)). The oily streak texture, like the focal conic domain, only appears in a lamellar phase, such as SmA, SmC or lyotropic lamellar. When macrocycle 67 was dissolved in a mixture of 1,2-dichloroethane and chloroform (1:3), a linear texture was found via POM (Figure 4.13b). The linear texture is identified as oil streak by comparison with n discotic nematic phase more concentrated bilayer lamellar phase  148 determinations in the literature.12   (a) (b) 200μm 200μm   Figure 4.13 (a) Polarized optical micrographs (50×) of 5 wt% 67 / 95 wt% 1,2-dichloroethane at room temperature. (b) Polarized optical micrographs (50×) of macrocycle 67 in a mixture of 1,2-dichloroethane / chloroform (1:3) at room temperature.  In addition to textures of Nd phase and lamellar phase observed at different concentrations, the phase transition between Nd and lamellar was found at room temperature from polarized optical micrographs (Figure 4.14).   149 isotropic Nd FCD dry film isotropic Nd FCD dry film 200μm 200μm Figure 4.14 Polarized optical micrographs (50×) of phase transition between Nd and focal conic texture.  4.2.2.2 Liquid Crystal Formed by Host-Guest Complex  Although there are many literature reports of liquid crystals formed by supramolecular assemblies,13 LC phases formed by inclusion complexes have been rarely reported. Mesogens assembled by inclusion complexes were, mainly, focusing on the formation of mesophases by the interaction between large flat aromatic cored molecules and relatively small acceptors which form stacked sandwich-like columnar π-π electron donar-acceptor complexes (Scheme 4.3).14      150 Scheme 4.3 Formation of columnar phase by an inclusion complex.  +   Unlike 67, no liquid crystallinity was observed for macrocycle 66 itself due to the shorter pentyloxy chains. However, when more than 1 equivalent of cetylpyridinium chloride 48+Cl, a guest with alkyl long tail, was added into the solution of 10 wt% 66 / 90 wt% chloroform, birefringence was observed by POM (Figure 4.15).   (a) (b) 500μm 200μm   Figure 4.15 Optical photomicrographs obtained for the mesophase of inclusion complex 48+⊂ 61 (a) Polarized optical micrographs (20×). (b) Polarized optical micrographs (50×)  151  It was first necessary to preclude the possibility that the liquid crystal is formed by pure cetylpyridinium chloride. When a solution of cetylpyridinium chloride / chloroform was sandwiched between two glass slides, no birefringence was observed by POM until all of the solvent evaporated. After the solution dried, only crystals were observed as shown in Figure 4.16.   Figure 4.16 Optical photomicrograph of crystals of cetylpyridinium chloride 48+Cl-.  Because macrocycle 66 does not form a liquid crystal phase itself, this mesophase should be formed by the inclusion complex 48+⊂61. According to the texture shown in Figure 4.15, a calamitic nematic phase (Nc) was obtained for the host-guest complex. Based on experimental data, people have built a model for the lyotropic nematic liquid crystals that are formed by amphiphiles.15 For disc-like amphiphilic molecules, they prefer to form rod-like micelles while rigid rod-like surfactant molecules preferably form disc-like micelles, as shown in Scheme 4.4.  152  Scheme 4.4 Model for assembly of amphiphilic molecules to form micelles. (a) Amphiliphilic molecules with a disc-like shape aggregate to rod-like micelles. (b) Amphiphiles with a rod-like shape aggregate to disc-like micelles. (a) (b)  When one equivalent of host and guest forms a complex, the shape of the complex can be regarded as a rod-like shape because of the long guest. According to this model, we propose the Nc mesophase formed by the host-guest complex is composed of disc-like micelles, as shown in Scheme 4.5.        153 Scheme 4.5 Proposed model for the formation of Nc phase by host-guest complex  Although no grid texture was found for the LC of complex in chloroform, an oily streak texture was observed in DCE (Figure 4.17). The presence of the oily streak texture indicates there is a lamellar phase formed, agreeing with the bilayer structure shown in Scheme 4.5.  Figure 4.17 Optical photomicrographs obtained with crossed polars for the mesophase of inclusion complex 48+⊂61 in 1, 2-dichloroethane. + micelle complex n calamitic nematic phase  154  4.3 Conclusions  Naphthalene-based [2+2] Schiff-base macrocycles that undergo keto-enol tautomerization were synthesized. These macrocycles proved to be supramolecular hosts for organic cations. At room temperature, naphthalene-based [2+2] macrocycles that incorporate dodecanoxyl chains form lyotropic liquid crystals in organic solvents with a nematic phase or lamellar phase, depending on the concentration. Macrocycles with pentyloxyl chains do not show lyotropic liquid crystalline phases at room temperature. However, when cetylpyridinium, a long amphiphilic guest, was added into a macrocycle with pentyloxyl chains, a lyotropic nematic phase was observed by POM. From the textures of these LLCs, I propose that a bilayer structure is the basis of these liquid crystals. From bilayer units, discotic or lamellar lyotropic phases form for naphthalene-based [2+2] macrocycles and calamitic lyotropic liquid crystalline phases can be formed for the host-guest complex assembled between macrocycle and cetylpyridinium.  4.4 Experimental  4.4.1 General  Chloroform, acetonitrile, and CDCl3 were dried over 3 Å molecular sieves. 2,3-Dihydroxy-1,4-diformylbenzene 2016and 2,3-dihydroxy-1,4-diformylnaphthalene 28,17 were prepared by literature methods. 1H and 13C NMR spectra were recorded on either a Bruker  155 AV-300 or AV-400 spectrometer. 1H and 13C NMR spectra were calibrated to the residual protonated solvent at δ = 7.24 and 77.00 ppm, respectively, in CDCl3 and δ = 5.91 and 74.2 ppm, respectively, in 1,1,2,2-tetrachloroethane-d2. 13C NMR spectra were recorded using a proton decoupled pulse sequence. 2D ROESY experiments were performed on a Bruker AV-400 spectrometer. UV-vis spectra were obtained on a Varian Cary 5000 UV-vis-near-IR spectrophotometer using a 1 cm quartz cuvette. IR spectra were obtained as neat in the solid state on a Thermo Nicolet 6700 FT-IR spectrometer. Electrospray ionization (ESI) mass spectra were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. The samples were analyzed in MeOH:CHCl3 (1:1) at 100 μM. MALDI-TOF mass spectra were obtained in a dithranol matrix (cast from THF) on a Bruker Biflex IV instrument where spectra were acquired in the positive reflection mode with delay extraction. Melting points were obtained on a Fisher-John’s melting point apparatus. Liquid crystal textures were observed with an Olympus BX41 polarizing optical microscope.  4.4.2 Synthesis and characterization  Synthesis of macrocycle 66. Compound 39 (0.186 g, 0.22 mmol) and compound 28 (0.047 g, 0.22 mmol) were dissolved in 120 mL of dry, degassed chloroform and 40 mL of dry, degassed acetonitrile. After the red solution was stirred at room temperature for 5 mins, piperidine (0.04 mL, 0.41 mmol) was added, resulting in a darkening of the solution. The resulting mixture was heated at reflux under nitrogen overnight. After cooling to room temperature, solvent was evaporated by rotary evaporation. Addition of methanol yielded a red precipitate that was  156 isolated by filtration. Recrystallization from chloroform/methanol afforded 0.078 g of 66 (0.038 mmol, 35%).  Data for 66. 1H NMR (400 MHz, CDCl3, 320 K): δ 14.85 (s, 4H), 14.67 (d, 4H), 8.76 (d, 4H), 7.69 (m, 4H), 7.19-6.88 (m, 26H), 6.62 (s, 4H), 6.60 (s, 2H), 6.18 (s, 4H), 3.92 (t, 8H), 3.62 (t, 8H), 1.97-0.90 (m, 88H) ppm. 13C NMR (100.6 MHz, 1,1,2,2-tetrachloroethane-d2, 343 K ): δ 174.40, 168.21, 152.31, 148.59, 147.93, 140.13, 134.99, 134.36, 133.46, 129.48, 128.87, 128.35, 128.26, 127.97, 127.13, 125.08, 120.22, 113.54, 111.51, 111.13, 107.27, 105.39, 99.87, 70.76, 70.19, 29.33, 29.04, 28.40, 28.33, 22.62, 22.53, 14.19 ppm. IR (neat): υ = 3300, 3055, 2951, 2928, 2867, 1614, 1548, 1503, 1465, 1319, 1256, 1180, 1124, 984, 915, 846, 740, 698, 555, 462 cm-1. UV-Vis (CH2Cl2): λmax (ε) = 479 (5.91×104), 382 (6.99×104), 289 (1.13×105) nm (L mol-1 cm-1). Anal. Calcd for C128H140N8O16·2H2O: C 73.82; H 6.97; N 5.38. Found: C 73.30; H 6.50; N 5.22. MALDI-TOF MS (dithranol matrix): m/z = 2047.1 [M+H]+. HRMS (ESI): C128H141N8O16 Calcd. 2046.0466, Found: 2046.0508. M.P.= dec. at 280 °C.  Synthesis of macrocycle 67. Compound 62 (0.20 g, 0.16 mmol) and compound 28 (0.035 g, 0.16 mmol) were dissolved in 120 mL of dry, degassed chloroform and 40 mL of dry, degassed acetonitrile. After the red solution was stirred at room temperature for 5 mins, piperidine (0.04 mL, 0.41 mmol) was added, resulting in a darkening of the solution. The resulting mixture was heated at reflux under nitrogen overnight. After cooling to room temperature, solvent was evaporated by rotary evaporation. Addition of ethanol yielded a red precipitate that was isolated by filtration. Recrystallization from chloroform/methanol afforded 0.086 g of 67 (0.033 mmol,  157 41%).  Data for 67. 1H NMR (400 MHz, CDCl3, 298 K) : δ 14.95 (s, 4H), 14.78 (d, 4H), 8.73 (d, 4H), 7.68 (m, 4H), 7.19 (m,4H), 7.06-6.89 (m, 22H), 6.60 (s, 4H), 6.59 (s, 2H), 3.91 (t, 8H), 3.58 (t, 8H), 1.76-0.83 (m, 184H) ppm. 13C NMR (100.6 MHz, CDCl3, 298 K): 173.8, 167.4, 151.6, 148.0, 147.1, 139.4, 133.7, 132.9, 128.8, 128.2, 127.7, 127.5, 127.2, 126.3, 124.3, 119.5, 113.0, 111.0, 110.6, 106.7, 104.8, 99.2, 70.1, 69.5, 28.7, 28.3, 27.7, 27.6, 21.9, 21.8, 13.5 ppm. IR: υ = 3300, 3050, 2948, 2930, 1618, 1550, 1503, 1447, 1320, 1250, 1181, 982, 850, 741, 699, 554, 422 cm-1. UV-Vis (CH2Cl2): λmax (ε) = 480 (5.62×104), 382 (6.68×104), 286 (1.09×105) nm (L mol-1 cm-1); Anal. Calcd for C184H252N8O16·3H2O: C 76.57; N 3.88; H 9.01. Found: C 76.53; N 3.83; H 8.89. MALDI-TOF MS (dithranol matrix): m/z 2831.8 [M+H]+, 2854.9 [M+Na]+, 2870.0 [M+K]+; M.P.= 232-235 oC.  Synthesis of macrocycle 72. In a Schlenk flask, compound 62 (0.28 g, 0.23 mmol), compound 25 (0.038 g, 0.23 mmol), and piperidine (0.04 mL, 0.41 mmol) were dissolved in 60 mL of dry CHCl3:CH3CN (2:1). The flask was fit with a condenser and the reaction mixture was refluxed overnight under N2. After cooling to room temperature, the solvent was removed under reduced pressure. The remaining solids were suspended in MeOH and filtered yielding a red powder. The crude product was recrystallized from CHCl3/MeOH giving 0.10 g of macrocycle 72 (0.036 mmol, 32%).   158 Data for [2+2] macrocycle 72. 1H NMR (400 MHz, CDCl3): δ 15.20 (s, 4H,), 12.89 (s, 4H,), 8.35 (s, 4H,), 6.95 (m, 26H), 6.61 (s, 4H), 6.52 (s, 2H), 6.15 (s, 4H), 3.92 (t, 8H,), 3.58 (t, 8H), 1.80-0.80 (m, 184H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 174.2, 169.5, 161.3, 151.2, 148.9, 148.1, 140.9, 135.7, 135.1, 128.9, 129.1, 128.8, 122.0, 121.8, 114.1, 109.2, 106.3, 106.1, 77.7, 71.8, 70.2, 30.2, 29.7, 29.3, 29.1, 29.0, 28.4, 23.5, 23.4, 15.0 ppm. UV-Vis (CH2Cl2) λmax (ε) = 439 (1.39 x 105), 388 (1.58 x 105), 338 (1.8 x 105), 285 (3.1 x 105) nm (cm-1 mol-1 L). IR (neat) υ = 3010, 2951, 2929, 2856, 1614, 1556, 1305, 1258, 992, 849, 740 cm-1. Anal. Calcd for C176H248N8O16·5H2O: C 74.91; N 3.97; H 9.22. Found: C 74.98; N 4.01; H 9.18. MALDI-TOF MS (dithranol matrix): m/z = 2732.8 [M+H]+. M.P.= dec. at 250 °C.  4.4.3 Characterization by Polarizing Optical Microscopy  The liquid crystal sample is normally sandwiched between two glass slides and loaded on the stage of the microscope. The polarized light then passes into the liquid crystal sample, and due to the birefringence properties of liquid crystal material, the light can partly pass through the analyzer, which is oriented at 90 degrees to the polarizer (cross-polarized). The liquid crystal texture can be observed by eye or recorded by a digital camera.  4.4.4  Simulation of Molecular Structure The structures of both macrocycles and host-guest complexes were simulated by semi-emperical methods with Sparton’04. The macrocycles were first constructed as coplanar  159 structures, then energy-minimized structures were obtained from different likely conformations. Energy-minimized structures were then subjected to PM3 calculation by setting the total charge as neutral for macrocycles and as cation for host-guest complexes.                     160 4.5 References   1 (a) Chambron, J.-C.; Meyer, M. Chem. Soc. Rev. 2009, 38, 1663. (b) Isaacs, L. Chem. Commun. 2009, 619. (c) Homden, D. M.; Redshaw, C. Chem. Rev. 2008, 108, 5086. 2 (a) Manley, J. M.; Roper, T. J.; Lash, T. D. J. Org. Chem. 2005, 70, 870. (b) Vagin, S.; Hanack, M. Eur. J. Org. Chem. 2003, 2661. (c) Kobayashi, N.; Nakajima, S.-I.; Ogata, H.; Fukuda, T. Chem. Eur. J. 2004, 10, 6294. 3 (a) Orda-Zgadzaj, M; Wendel, V; Fehlinger, M; Ziemer, B; Abraham, W. Eur. J. Org. Chem. 2001, 1549. (b) Arduini, A; McGregor, W. M.; Paganuzzi, D.; Pochini, A.; Secchi, A.; Ugozzoli, F.; Ungaro, R. J. Chem. Soc., Perkin Trans. 2, 1996, 839. 4 Sauer, M; Yeung, C; Chong, J. H.; Patrick, B. O.; MacLachlan, M. J. J. Org. Chem 2006, 71, 775. 5 Kagarise, R. E. J. Am. Chem. Soc. 1955, 77, 1377 6 Clifford, A. F. J. Phys. Chem. 1959, 63, 1227 7 (a) Sato, T.; Tsuneda, T.; Hirao, K. J. Chem. Phys. 2005, 123, 104307. (b) Cubero, E; Orozco, M.; Luque, F. J. J. Phys. Chem. A 1999, 103, 315 8 The binding constant was obtained using the curve fitting program Sigmaplot 10 and EQNMR (Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.) Both methods gave essentially the same result. 9 (a) Dalcanale, E.; Du. Vosel, A.; Levelut A. M.; Malthete, J. Liq. Cryst. 1991, 10, 185. (b) Hoger, S.; Cheng, X. H.; Ramminger, A.; Enkelmann, V.; Rapp, A.; Mondeshki M.; Schnell, I.  161  Angew. Chem., Int. Ed. 2005, 44, 2801. (c) Zhang J.; Moore, J. S. J. Am. Chem. Soc. 1994, 116, 2655. 10 (a) Pidwell, A. D.; Collinson, S. R.; Coles, S. J.; Hursthouse, M. B.; Schroder M.; Bruce, D. W. Chem. Commun. 2000, 955. (b) Brandys F. A.; Pugh, C. Macromolecules 1997, 30, 8153. (c) Nesrullajev, A.; Bilgin-Eran, B.; Kazanci, N. Mater. Chem. Phys. 2002, 76, 7. 11 Nesrullajev, A.; Kazanci, N. Mater. Chem. Phys. 2000, 62, 230. 12 Zappone B.; Lacaze, E. Phys. Rev. E 2008, 78, 061704. 13 (a) Imam, M. R.; Peterca, M.; Edlund, U.; Balagurusamy, V. S. K.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 4165. (b) Lehmann, M. Chem. Eur. J. 2009, 15, 3638. 14 (a) Cladis, P. E. Mol. Cryst. Liq. Cryst. 1981, 67, 177. (b) Demus, D.; Pelzl, G.; Sharma, N. K.; Weissflog; W. Mol. Cryst. Liq. Cryst. 1981, 76, 241. (c) Ringsdorf, H.; Wtistefeld, R.; Zerta, E.; Ebert, M.; Wendorff, J. H. Angew. Chem. Int. Ed. 1989, 28, 914. 15 Luhmann, B.; Finkelmann, H. Colloid Polym. Sci., 1986, 264, 189. 16 Akine, S; Taniguchi, T.; Nabeshima, T. Tetrahedron Lett. 2001, 42, 8861. 17 Gallant, A. J.; Yun, M.; Sauer, M.; Yeung, C. S.; MacLachlan, M. J. Org. Lett. 2005, 7, 4827.  162 Chapter 5  Synthesis and Characterization of a Conjugated Metal-containing Poly(p-phenylenevinylene) Analogue*  5.1 Introduction  Conjugated polymers have been the subject of intense research since the discovery in 1977 that doped polyacetylene is metallic.1 The conjugation in these organic materials is facilitated by unsaturated bonding within the backbone that enables delocalization of electrons within the π-orbitals, and gives rise to a band structure. In general, the conjugation in organic polymers is limited by defects and rotation of bonds within the polymer backbone. By limiting the rotation of the components in the conjugated polymer, the conjugation may be extended, improving the extent of exciton delocalization and charge carrier migration.2 Efforts to hinder rotation have included using conjugated and saturated linkers between segments of the backbone.3 Metal complexation may be used to modify the conjugation4; indeed, Swager and coworkers have used this mechanism to inhibit the conjugation in polythiophene segments, leading to measureable property changes that can be used in sensing.5   * A version of this chapter has been published: Jiang, J.; Leung, A. C. W.; MacLachlan, M. J. “Synthesis and Characterization of an Oligomeric Conjugated Metal-Containing Poly(p-phenylenevinylene) Analogue” Dalton. Trans. 2010, 39, 6503.  163 There is a growing interest in the synthesis and characterization of metal-containing conjugated polymers due to their potential in materials science. In addition to affecting the conformation of the polymer, the introduction of a metal center into the conjugated polymeric chain may produce a range of characteristics that differ from those of conventional organic polymers, e.g. redox, magnetic, optical and electronic properties.6  Incorporation of chromophores such as Schiff-base complexes into polymers has been investigated for potential applications in catalysis7 and light-emitting diodes (LEDs).8 Schiff-base complexes incorporated into polymers via electropolymerization offer binding sites for the 4-electron reduction of oxygen to water.9 Our group has reported conjugated poly(p-phenyleneethynylene)s that incorporate Schiff-base complexes of Ni2+, VO2+, Zn2+, and Cu2+.10 Although intractable conjugated polymers containing Schiff-base complexes in the backbone are known, we were able to ensure solubility with the use of long alkyl substituents.  The lack of viable synthetic routes to conjugated metal-containing polymers, as well as the difficulty of producing soluble polymers, has impeded progress in this field. Since the discovery of electroluminescence in poly(p-phenylenevinylene) (PPV, 74) in 1990, 11  many derivatives of PPV have been prepared, particularly for application in light-emitting diodes (LEDs).12 PPV derivatives with bulky alkoxy side groups have been most extensively studied as their presence enhances both solubility and quantum efficiency.13 Various approaches to synthesize soluble dialkoxy PPVs have been reported in the literature including the Gilch route, 14  the Wittig reaction, 15  and aryl-ethylene coupling via Heck or Suzuki reactions.16 Among these methods, the Gilch route is commonly used because it is a simple one-pot process. In the Gilch polymerization route, a 1,4-bis(halogenomethyl)benzene structure  164 73 is postulated to undergo an elimination reaction to form a quinodimethane intermediate that polymerizes, as shown in Scheme 5.1.17 In a second step, E2 elimination of HBr affords the conjugated PPV. Most research based on the synthesis of PPV by the Gilch route has focused on changing the functional groups on the monomer precursor in order to form the quinodimethane intermediate more readily. A few papers have reported the synthesis of poly(fluorenevinylene) derivatives by Gilch polymerization in which electrons transfer over four double bonds to give the quinodimethane intermediate.18 Only two papers show a more complicated system, where researchers attempted to incorporate porphyrin units19 and 1,3,4-oxadiazole segments20 into the copolymer backbone. These copolymers were found to contain less than 2 mol % of porphyrin and less than 30% of oxadiazole segments. It was not possible to include larger quantities of porphyrin and oxadiazole into the polymer due to solubility limitations.  Scheme 5.1 Postulated Mechanism for Gilch Polymerization Route to PPV 74. 73 74 In this chapter, the design and synthesis of a new Schiff-base metal complex that functions as a monomer for the preparation of a metal-containing PPV analogue is described. The synthesis and  165 characterization of the conjugated homo-oligomer, as well as a new conjugated model compound, are discussed. During the formation of the quinodimethane intermediate in our system, an elimination reaction over six double bonds must occur.  5.2 Results and Discussion  The best method to ensure complete metallation of a conjugated polymer is to polymerize the metal-containing monomer, rather than by post-polymer modification. We proposed to synthesize a new monomer 75 (Figure 5.1) containing two benzylbromide substituents as a possible precursor to metallo-PPV. This monomer features branched, chiral alkoxy groups for solubility and a square planar nickel(II) center to maintain planarity and, thus conjugation, in the monomer. In this monomer, the elimination reaction would result in an elimination reaction over a distance of 16 atoms, as will be discussed.  OO N N O O Ni BrBr 275 Figure 5.1 Structure of monomer 75.   166 In order to synthesize monomer 75, 4-bromomethyl-2-hydroxybenzaldehyde 80, a previously unknown compound, was required. Although 5-halomethyl-2-hydroxybenzaldehyde can be prepared easily by chloro- or bromomethylation of salicylaldehyde,21 it would be much more difficult to obtain the isomer we desired in 80.  Scheme 5.2 Synthesis of compound 80.  OMe NBS, hv CCl4, 4h, 54% OMe Br Br NaOMe THF, reflux 2h, 95% OMe OMe MeO DDQ DCM+H2O R.T., overnight OMe MeO O BBr3 DCM, -78oC to R.T. overnight, 24% from last two steps OH O H Br 3 4 56 76 77 78 7980 OMe OMe O ( ) isomer   Scheme 5.2 illustrates our route to compound 80. 1,4-Bis(bromomethyl)anisole 77 was prepared via double free-radical bromination of commercially available 1,4-dimethylanisole 76 according to a literature procedure. 22  Compound 77 was then converted into 1,4-bis(methoxymethyl)anisole 78 in nearly quantitative yield upon treatment with excess sodium methoxide in THF. 23  Selective oxidation of compound 78 with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in 10:1 DCM:H2O afforded 2-methoxy-4-(methoxymethyl)benzaldehyde 79.  In this reaction, the product obtained is a mixture of 79 and its isomer 3-methoxy-2-(methoxymethyl)benzaldehyde in the ratio of 5:1. As  167 the separation of the isomers was difficult at this stage, the compound was used for the next step without purification. In the final step, a simultaneous deprotection of the phenol as well as the benzyl methyl ether with BBr3 gave the new compound 2-hydroxy-4-(bromomethyl)benzaldehyde 80. It is noteworthy that compound 80 is relatively unstable; attempts to concentrate it by rotary evaporation at > 30-40 ºC resulted in decomposition to a thick, brown paste with visible HBr production. This product could be purified by flash column chromatography (DCM : Hexane = 1 : 2, SiO2) and readily separated from the other isomer, and stored in the fridge. Schiff-base condensation of salicylaldehyde derivative 80 with 4,5-diamino-1,2-bis(2-ethylhexyloxy)benzene 81 in the presence of nickel(II) acetate yielded monomer 75 in 65% yield, Scheme 5.3. The 1H NMR spectrum of 75 was extremely broad in CDCl3, suggesting strong aggregation that results in a decrease of the T2 relaxation time for the protons. Upon addition of a trace of THF-d8, sharp peaks were observed and could be assigned to the resonances of the protons expected for compound 75. In particular, the imine resonance was observed at 7.74 ppm, and the bromomethyl substituents were present as a singlet at 4.35 ppm. The elemental analytic, mass spectrometric, and IR spectroscopic data were also consistent with the complex.        168 Scheme 5.3 Synthesis of monomer 75.  OH O H Br THF, R.T., 2d, 65% 6 Ni(OAc)2 7 2 + OO H2N NH2 2 80 81 75   Polymerization of 75 with an excess of tBuOK in the mixture of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF) afforded the new polymer 82, Scheme 5.4. The low yield was attributed to the formation of a gel that would not dissolve in any common solvent. Gelation is a well established problem for Gilch polymerization reactions, but the source of its formation remains under discussion.24 Our attempts to obtain polymer 82 were severely frustrated by gel formation. Researchers have published the polymerization procedure under many different conditions to overcome the gelation, several of which were tried in order to optimize the preparation of polymer 82.25 Table 5.1 summarizes some of the conditions tried with limited success to obtain the soluble polymer. In general, most of the procedures afforded exclusively or primarily insoluble material. In an attempt to terminate the end groups with p-tert-butylbenzyl groups, p-tert-butylbenzylchloride was added to the reaction (entry #3), but still only insoluble material was obtained.    169 Scheme 5.4 Synthesis of polymer 82.        OO N N O O Ni Br O O  During the polymer preparation, I became concerned that tBuOK could react with the imine on the monomer, possibly destroying the complex during the reaction. Deprotonation of the imine functionality with tBuOK has been reported.26 To test whether this was a problem, a simple nickel(II) salphen molecule was reacted under similar conditions to monomer 75 with excess tBuOK. After the experiment, the reaction was quenched with wet methanol and the product was analyzed. 1H NMR spectroscopy indicated that the complex was stable, though it is possible that the monomer was deprotonated during the polymerization reaction, and this could be one cause of the gel formation.     Br THF+DMF, R.T.,  2d, 34% N N Ni O O n 2 8 t BuOK 75 82  170 Table 5.1 Summary of polymerization attempts to obtain polymer 82. # Solvent Reagents T Yielda Mnb 1 THF tBuOK 50 oC all gelation - 2 THF tBuOK R.T. 10% 3303 3 THF tert-butylbenzylchloride + tBuOK R.T. all gelation - 4 THF KOH + Bu4NBr 0 oC less than 5% 244 5 DMF tBuOK 50 oC all gelation - 6 DMF tBuOK R.T. 73% 1001 7 DMF+THF tBuOK R.T. 34% 5559 a Yield of soluble fraction. b Measured by GPC (THF) relative to polystyrene standards  The Gilch polymerization is much more complicated in our system than in previously reported systems. Whereas typically the elimination reaction proceeds over a single benzene ring as for PPV (Scheme 5.1), the elimination reaction to afford a quinodimethane intermediate must occur through the entire structure in 75. Positioning the benzylic halide groups on para to the imine groups would allow electron transfer through the entire ligand system to occur, giving the quinodimethane-like intermediate. The postulated intermediate is illustrated in Scheme 5.5.        171 Scheme 5.5 The formation of quinodimethane-like intermediate  N N O O O O BrBr Ni H H OtBu O O N N O O Ni BrH HH   Based on my experiments, polymerization in a mixture of THF and DMF gave less gelation and higher molecular weight than in pure THF or DMF. The resulting red polymer is soluble in THF and DCM, and was characterized by gel permeation chromatography (GPC), elemental analysis, and thermogravimetric analysis (TGA), as well as UV-Vis, IR, and NMR spectroscopies. GPC of the polymer (Figure 5.2a) indicated a molecular weight of ca. 5600 Da (Mn), indicating that the polymer contains only 7-8 repeat units in its structure. Strictly speaking, the product obtained can only be regarded as oligomers instead of polymer. Nevertheless, this is still respectable for conjugated metallopolymers, which are rarely soluble and generally synthesized in low molecular weights. The required electron transfer / elimination reaction through the entire ligand during the polymerization may also inhibit polymerization and prevent the generation of high molecular weight polymer. Elemental analysis was also consistent with ca. 3-4 repeat units in the polymer, assuming terminal CH2Br substituents.  From previous work in our group, elemental  172 analysis of metal-containing polymers often underestimates the amount of carbon present in the polymer, possibly due to incomplete combustion or coordination of water. (a) 0 1 2 3 4 5 6  Figure 5.2 (a) GPC result of oligomer 82. (b) Thermogravimetric analysis of oligomer 82.  TGA of the oligomers 82 (Figure 5.2 b) showed decomposition at 250 ºC, and that was 50 ºC higher than for the monomer. The char that remained (11.4 mass %) corresponds to the expected mass if the product was primarily NiO. Temperature ( oC ) (b) W ei gh t ( m g) 88.6% 11.4% 0 200 400 600 800  173 Figure 5.3a displays the 1H NMR spectrum of 82. The spectrum of 82 is very broad, suggestive of aggregation, and, unlike the spectrum for 75, the spectrum for 82 does not become sharp upon addition of coordinating solvents such as THF. The 1H NMR spectrum of the oligomer in THF-d8 is consistent with the proposed structure and indicates the absence of residual monomer or short oligomers that would be expected to show sharp resonances. A broad peak at 7.6-8.0 ppm is assigned to the imine resonance. A broad peak between 6 and 7.5 ppm is attributed to the protons of aromatic and ethylene groups. There is also a small peak at 3.9 ppm assigned to protons on -OCH2. No peak was observed near 4.35 ppm, where the CH2Br peak in monomer 75 was located, but it may be very weak if only due to end groups in the polymer. The aggregation of the polymer prevented me from obtaining useful 13C NMR data for the oligomer. 16 94 .6 (b) Polymer Monomer ppm (a) 1500 wavenumber (cm-1) 1694.6 (a) (b) polymer 82 monomer 75 16 94 .6 16 94 .6 567891011 pm  Figure 5.3 (a) NMR Spectra of oligomer 82 (400 MHz, CD2Cl2, 298 K). (b) IR spectrum of oligomer 82 and monomer 75 (around 1500 cm-1).   174 Comparison of the IR spectra obtained from the oligomer and the monomer confirms that the Schiff-base complex is still intact in the polymer. The C=N vibration appears at 1602 cm-1 in the oligomer. A peak at 1275 cm-1 is attributed to the C-O stretching vibration of the phenol structure. Two bands observed near 530 cm-1 and 455 cm-1 belong to the vibration of Ni-O and Ni-N, respectively. Importantly, compared to the IR of monomer, a new peak appears at 1694.6 cm-1 in IR spectrum of the oligomer. This medium strength band is probably due to the C=C stretching vibration of PPV chains. The band observed in the both monomer and compound 80 at 669 cm-1, which is assigned to the C-Br stretch vibration, is absent in the IR spectrum of the oligomer. To provide further confirmation of the oligomer structure, model compound 83 was prepared by the procedure shown in Scheme 5.6. Treatment of monomer 75 with triphenylphosphine in DMF afforded the Wittig reagent 84. Condensation with benzaldehyde gave distilbene model compound 83 in 72% yield. NMR and MS data for this compound were in agreement with its structure. (The 1H NMR and 13C NMR spectrum of 83 are messy due to the formation of both trans- and cis- double bonds during Wittig reaction.) Figure 5.4 displays the UV-vis spectra of 82, together with the spectra of monomer 75 and model compound 83. Compared to the spectrum of monomer 75, the UV-Vis absorption spectrum of 82 was broader and slightly red-shifted, consistent with extended conjugation. The bandgaps calculated from the UV-Vis spectra are 2.0 eV and 2.2 eV for the oligomer and the monomer, respectively. Overall, the features in the visible region of the spectrum are similar for the monomer, the oligomer, and the model compound.  These are quite likely dominated by charge-transfer bands within the metal complex.   175 Scheme 5.6 Synthesis of model compound 83. 75 N N O O O O Ni BrBr PPh3 DMF, refluxing, 12h, 56% N N O O O O Ni PPh3Ph3P Br-Br- N N O O O O Ni O t BuOK THF+EtOH, R.T., 12h, 72% 84 83  Wavelength (nm) 300 400 500 600 700 A bs or ba nc e 0.0 .5 1.0 1.5 2.0 monomer oligomer model  Figure 5.4 UV-Vis spectra (1.0 cm cell, 298 K, CH2Cl2) of monomer 75, oligomer 82, and model compound 83.  176  5.3 Conclusions  In this chapter, I discussed the synthesis and characterization of a new conjugated oligomer. During the synthesis of the conjugated oligomer, a synthesis of a new compound 2-hydroxy-4-(bromomethyl)benzaldehyde 80 was achieved in 4 steps. This compound was condensed with a diamine to give a new Schiff-base complex with two bromomethyl groups, which is a useful compound to synthesize metal-containing polymers or other conjugated structures. Efforts to obtain soluble conjugated polymer by Gilch polymerization were frustrated by gelation, but oligomers could be obtained. A model compound for the PPV-analogue was also prepared for spectroscopic comparison.  5.4 Experimental  5.4.1 General  Materials. 2,5-Dimethylanisole, sodium methoxide (25% in methanol), N-bromosuccinimide (NBS), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), boron tribromide (BBr3), nickel(II) acetate, and triphenylphosphine (PPh3) were obtained from Aldrich. Deuterated solvents were obtained from Cambridge Isotope Laboratories, Inc. Tetrahydrofuran was distilled from sodium / benzophenone under N2. 2,5-Di(bromomethyl)anisole 77,  177 2-methoxy-4-(methoxymethyl)benzaldehyde 78, and 4,5-diethylhexyloxy-1,2-phenylenediamine 8127 were prepared by literature methods.  Equipment. All reactions were carried out under a nitrogen atmosphere using Schlenk techniques or in a N2 glovebox (MBraun) unless otherwise noted. 1H and 13C NMR spectrum were recorded on either a Bruker AV-300 or AV-400 spectrometer. UV-Vis spectra were obtained in distilled THF on a Varian Cary 5000 UV-Vis/near-IR spectrometer using a 1 cm quartz cuvette. IR spectra were obtained as neat in the solid state on a Thermo Nicolet 6700 FT-IR spectrometer. Molecular weights were estimated by gel permeation chromatography (GPC) in THF using a Waters liquid chromatograph. Narrow molecular weight polystyrene standards were used for calibration purposes. Electrospray ionization (ESI) mass spectra were obtained at the UBC Microanalytical Services Laborary on a Micromass LCT time-of-flight (TOF) mass spectrometer. MALDI-TOF mass spectra were obtained in a dithranol matrix (cast from THF) on a Brüker Biflex IV instrument where spectra were acquired in the positive reflection mode with delay extraction. Melting points were obtained on a Fisher-John’s melting point apparatus.  5.4.2 Synthesis and Characterization  Synthesis of 2-hydroxy-4-(bromomethyl)benzaldehyde 80. Compound 78 (1 g, 3.4 mmol) was added to a mixture of 10:1 dichloromethane:water (300 mL). DDQ (1.15 g, 5.0 mmol)  was added to the above system and the reaction mixture was vigorously stirred at room temperature overnight. The red mixture was then poured into saturated aqueous sodium bicarbonate and stirred for 30  178 mins. After the mixture separated, the aqueous layer was extracted with dichloromethane (3 x 50 mL). The combined organic fractions were washed with brine then water, and dried over MgSO4. After filtration and concentration by rotary evaporation, the crude product was used for the next step without further purification. 1H NMR indicated that the product was a mixture of 2-methoxy-4-(methoxymethyl)benzaldehyde and 3-methoxy-4-(methoxymethyl)benzaldehyde, but the product was not easily separated at this stage. Under an atmosphere of nitrogen the crude product from above was dissolved in 200 mL of anhydrous dichloromethane. The solution was cooled by dry ice/acetone and 1 mL of BBr3 (10 mmol) was added. The red solution was stirred overnight allowing the reaction mixture to slowly warm to room temperature. After pouring the reaction onto ice, the product was extracted with dichloromethane (3 x 50 mL). The combined organic fractions were dried over MgSO4, filtered, and dried by rotary evaporation. During rotary evaporation, the temperature of the water bath must be lower than 30 °C to prevent rapid decomposition. The crude yellow solid was purified by flash column chromatography on silica with DCM:hexane= 1:2, then dried by rotary evaporation at low temperature to afford a yellow solid. The compound decomposes at room temperature and must be kept in the fridge. Yield: 0.17 g (0.78 mmol, 24 %) based on 2 steps.  Data for 80. 1H NMR (400 MHz, CDCl3): δ 11.04 (s, 1 H), 9.87 (s, 1 H), 7.55 (d, 1 H), 7.02 (d, 1H), 6.99 (s, 1H), 4.40 (s, 2H) ppm. 13C NMR (100.6 MHz, CDCl3): δ 196.1, 161.9, 147.1, 134.4, 120.8, 120.5, 118.2, 31.9 ppm. UV-Vis (CH2Cl2): λmax = 227, 268, 335 nm. IR (neat): υ = 3200, 1654, 1565, 1502, 1448, 1436, 1388, 1287, 1224, 1189, 1128, 1012, 974, 868, 802, 745, 664, 558,  179 453 cm-1 Anal. Calc’d for C8H7BrO2: C, 44.68; H, 3.28 Found: C, 44.35; H, 3.39. EI-MS: m/z 214, 216 [M]+, 135 [M- CH2Br]+. M.P.: 50 oC (dec.)  Synthesis of monomer 75. A solution of 75 (0.144 g, 0.66 mmol) and 81 (0.122 g, 0.33 mmol) in degassed THF (20 mL) was stirred under N2 at room temperature overnight. Nickel(II) acetate tetrahydrate (0.08 g, 4.5 mmol) was added and the red solution was stirred for an additional 12 h at room temperature. The solution was poured into 150 mL methanol, yielding a red precipitate. The precipitate was collected by filtration and reprecipitated two more times for purification. Yield: 0.15 g (0.18 mmol, 56%).  Data for 75. 1H NMR (400 MHz, trace of THF-d8 in CDCl3): δ 7.78 (s, 2 H), 7.12 (d, 2H), 7.02 (s, 2 H), 6.97 (s, 2H), 6.65 (d, 2H), 4.35 (s, 4H), 3.95 (d, 4H) 1.8-0.9 (m, 30 H) ppm. 13C NMR (100.6 MHz, trace of THF-d8 in CDCl3): δ 165.2, 151.6, 150.4, 144.0, 136.3, 134.1, 121.9, 120.3, 116.6, 98.4, 77.4, 72.1, 39.9, 33.9, 30.8, 29.4, 24.2, 23.3, 14.3, 11.5 ppm. UV-Vis (DCM): λmax = 263, 301, 391, 487 nm. IR: υ = 3051, 3017, 2955, 2921, 2856, 1607, 1584, 1518, 1440, 1370, 1276, 1188, 1117, 1030, 944, 867, 824, 787, 744, 669, 617, 542, 458 cm-1. Anal. Calcd for C38H48Br2N2NiO4: C, 55.98; H, 5.93; N, 3.44. Found: C, 55.58; H, 6.27; N, 3.84. ESI- MS: m/z 837 [M+Na]+. M.P.=160-162 oC.  Synthesis of oligomer 82. To a stirred solution of monomer 75 (0.2 g, 0.25 mmol) in anhydrous THF (10 mL) and anhydrous DMF (10 mL) was added a solution of tBuOK (0.05 g, 4.5 mmol) in anhydrous THF (5 mL). The resulting mixture was stirred for 48 h at room temperature before it  180 was poured into methanol (150 mL). The red solid was collected by filtration and washed with methanol, then stirred in hexane at room temperature for 1 h. After drying in the funnel, the crude product was placed in a Soxhlet extractor and extracted into hot THF over 2 d. After cooling, the THF was removed by rotary evaporation to give 0.055 g of a dark red solid (34 %).  Data for 82. 1H NMR (400 MHz, CDCl3): δ 9.0-8.2 (br), 8.0-6.4 (br), 4.0-3.6 (br) 1.8-0.9 (br). It was not possible to obtain a 13C NMR spectrum. UV-Vis: λmax = 225, 394 nm. IR: υ = 3052, 3014, 2952, 2921, 2853, 1694, 1602, 1501, 1463, 1361, 1275, 1177, 1007, 866, 790, 723, 609, 530, 455 cm-1. Anal. Calcd for C76H96N4Ni2O10: C, 69.41; H, 7.66; N, 4.26. Found: C, 64.27; H, 7.24; N, 4.18.  Synthesis of complex 84. A mixture of 75 (0.33 g, 0.4 mmol) and PPh3 (0.21 g, 0.8 mmol) in 40 mL of anhydrous DMF was heated to reflux for 8 h under nitrogen. After cooling to room temperature, the reaction mixture was poured into diethyl ether. The precipitate was collected on a Buchner funnel, washed with 100 mL of diethyl ether, and dried under vacuum. Yield: 0.26g (0.24 mmol, 56%).  Data for 84. 1H NMR (DMSO-d6 ): δ 8.92 (s, 2H), 7.3-7.9 (m, 48H), 6.65 (s, 2H), 6.10 (d, 2H), 5.09 (d, 4H), 3.95 (t, 4H), 0.8-1.8 (m, 30H) ppm. 13C NMR( DMSO-d6 ): δ 163.9, 153.8, 150.6, 136.1, 135.2, 134.5, 130.5, 123.0, 121.2, 118.5, 117.7, 99.77, 77.4, 39.9, 31.3, 29.4, 23.9, 23.3, 14.3, 11.6 ppm. 31P NMR (DMSO-d6, 8% H3PO4 aqueous as external reference): δ = 23.45 ppm. UV-Vis: λmax = 259, 389 nm. IR: υ = 3053, 3013, 2953, 2925, 2858, 1602, 1512, 1435, 1374, 1278,  181 1191, 1109, 995, 870, 806, 743, 716, 687, 646, 606, 531, 503, 461 cm-1. Anal. Calc’d for C74H78Br2N2NiO4P2: C, 66,33; H, 5.87; N, 2.09. Found: C, 63.54; H, 5.91; N, 2.24. HRMS (ESI): C74H77N2NiO4P2 Calc. 1177.4790, Found 1177.4712. M.P.=260 oC (dec.)  Synthesis of model compound 83. To a mixture of compound 84 (0.1 g, 0.07 mmol) of and benzaldehyde (0.015 g, 0.14 mmol) was added 10 mL of dry THF and 10 mL of dry DMF. The mixture was stirred at R.T. for 10 mins until the solid was dissolved. tBuOK (0.05 g, 0.45 mmol) was dissolved in 5 mL of dry THF. tBuOK solution was added by syringe into the solution of 84 and benzaldehyde. After stirring for 8 h, the reaction mixture was poured into methanol. The precipitate was recovered by filtration and washed with 10 mL methanol. Yield: 0.042 g (0.05 mmol, 72%).  Data for 83. 1H NMR (CD2Cl2 ): δ 8.02 (br, 2H), 6.90-7.60 (br, m, 22H), 3.95 (br, 4H), 0.8-1.5 (br, 30H). 13C NMR (CDCl3 ): δ 165.8, 151.6, 150.0, 143.6, 137.3, 136.3, 133.3, 132.5, 131.6, 130.4, 129.36, 128.8, 128.3, 127.5, 127.1, 122.2, 120.4, 119.9, 116.9, 114.2, 98.5, 77.4, 72.2, 39.8, 30.8, 29.4, 24.1, 23.3, 14.3, 11.5. UV-Vis: λmax = 301, 406, 495nm. IR: υ = 3055, 3023, 2953, 2923, 2856, 1601, 1581, 1515, 1463, 1434, 1361, 1276, 1181, 1112, 1026, 958, 875, 778, 689, 634, 593, 529, 454 cm-1. Anal. Calcd for C52H58N2NiO4: C, 74.91; H, 7.01; N, 3.36. Found: C, 71.67; H, 6.81; N, 3.43. HRMS (ESI): C52H58N2NiO4 Calc. 833.3750, Found 833.3828. M.P.=125-130 oC     182  5.5 References    1 (a) Chiang, C. K.; Druy, M. A.; Gau, S. C.; Heeger, A. J.; Louis, E. J.; MacDiarmid, A. G.; Park, Y. W.; Shirakawa, H. J. Am.Chem. Soc. 1978, 100, 1013. (b) Bates, F. S.; Baker, G. L. Macromolecules 1983, 16 , 1013. (c) Su, W. P.; Schrieffer, J. R.; Heeger, A. J. Phys. Rev. Lett. 1979, 42, 1698 . (d) Chien, J. C. W. Polyacetylene: Chemistry, Physics, and Materials Science, Academic Press Inc., 1984. (e) Skotheim, T. A.; Reynolds. J. R. Conjugated polymer; processing and applications, 3d ed., CRC / Taylor & Francis, 2007. (f) Jenekhe, S. A.; Osaheni, J. A. Science 1994, 265, 765. 2 (a) Schwartz, B. J. Annu. Rev. Phys. Chem. 2003, 54, 141. (b) Grozema, F. C.; Duijnen, P. Th. V; Berlin, Y. A.; Ratner, M. A.; Siebbeles, L. D. A. J. Phys. Chem. B 2002, 106, 7791. 3 Baughman, R. H.; Bredas, J. L.; Chance, R. R.; Elsenbaumer, R. L.;.Shacklette, L. W. Chem. Rev. 1982, 82, 209. 4 (a) Wolf, M. O.; Wrighton, M. S. Chem. Mater. 1994, 6, 1526. (b) Cameron, C. G.; Pickup, P. G. J. Am. Chem. Soc. 1999, 121, 7710. (c) Clot, O.; Wolf, M. O.; Patrick, B. O. J. Am. Chem. Soc. 2001, 123, 9963. 5 (a) Zhou, S. S.; Swager, T. M. Adv. Mater. 1996, 8, 497; (b) Zhou, S. S.; Kingsborough, R. P.; Swager, T. M. J. Mater. Chem. 1999, 9, 2123. 6 (a) Weder, C. Chem. Commun. 2005, 5378. (b) Whittell G. R.; Manners, I. Adv. Mater. 2007, 19,  183  3439. (c) Abd-El-Aziz, A. S.; Manners, I. Frontiers in Metal-Containing Polymers, Wiley, Hoboken, NJ, 2007. (d) Kingsborough, R. P.; Swager, T. M. Prog. Inorg. Chem. 1999, 48, 123. 7 (a) Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Singh, S.; Ahmed I; Jasra, R. V. J. Mol. Catal. A: Chem 2004, 218, 141. (b) Vilas-Boas, M.; Freire, C.; Castro, B. B.; Hillman, A. R. J. Phys. Chem. B 1998, 102, 8533. 8 (a) Chen H.; Archer, R. D. Macromolecules 1996, 29, 1957. (b) Wu, H. C.; Thanasekaran, P.; Tsai, C. H.; Wu, J. Y.; Huang, S. M.; Wen, Y. S.; Lu, K. L. Inorg. Chem. 2006, 45, 295. (c) Gustafsson, G.; Cao, Y.; Treacy, G. M.; Klavetter, F.; Colaneri, N.; Heeger, A. J. Nature 1992, 357, 477. (d) Blouim, N.; Michaud, A.; Leclerc, M. Adv. Mater. 2007, 19, 2295–2300. 9 El-Sonbati, A. Z.; El-Bindary, A. A.; Rashed, I. G. A. Spectrochim. Acta, Part A 2002, 58, 1411. 10 Leung, A. C. W.; Chong, J. H.; Patrick, B. O.; MacLachlan, M. J. Macromolecules 2003, 36, 5051. 11 Burroughes, J. H.; Bradley, D.D.C.; Holmes, A.B. Nature 1990, 347, 539. 12  (a)Friend, R. H.; Gymer, R. W.; Holmes, A. B.; Rurroughes, J. H.; Mark, R. N.; Tiliani, C.; Bradley, D. D. C.; Dos Santos, D. A.; Bredas, J. L.; Logdlund, M.; Salaneck, W. Nature 1999, 397, 121. (b) Shin, H.K.; Jin, J.L. Adv. Polym. Sci. 2002, 158, 194. 13 (a) Doi, S.; Kuwabara, M.; Noguchi, T.; Ohshino, T. Synth. Met. 1991, 55, 4174. (b) Ohshimura, Y.; Uchida, M.; Muro, K.; Yoshino, K. Jpn. J. Appl. Phys. 1991, 30, L1938. 14 (a) Gilch, H. G.; Wheelwright, W. L. J. Polym. Sci., A, Polym. Chem. 1996, 4, 1337. (b) Fan, Q.-L.; Lu, S. Macromolecules 2003, 36, 6976. (c) Schwalm, T.; Rehahn, M. Macromolecules 2007, 40, 3921.  184  15 (a) Drefahl, G; Kuchmstedt, R.; Oswald, H.; Horhold, H. H. Macromol. Chem. 1970, 131, 89. (b) Smith, R. C.; Chen, X.; Protasiewicz, J. D. Inorg. Chem. 2003, 42, 5468. (c) Yang, Z.; Hu, B.; Karasz, F. E. Macromolecules 1995, 28, 6151. 16 (a) Friend, R. H.; Denton, G. J.; Halls, J. J. M. Synth. Met. 1997, 84, 463. (b) Okawa, H.; Wada, T.; Sasabe, H. Synth. Met. 1997, 84, 265. (c) Jung, S.H.; Kim, H. K.; Kim, S. H.; Jeong, S. C.; Kim, Y. H.; Kim, D. Macromolecules 2000, 33, 9277. (d) Suzuki, A.; Miyaura, N. Chem. Rev. 1995, 95, 2457. 17 Kraft, A.; Grimsdale, A.C.; Holms, A.B. Angew. Chem. Int. Ed. 1998, 37, 402. 18 (a) Hwang, D.H.; Lee, J.D.; Jin S.H. J. Mater. Chem. 2003, 13, 1540. (b) Jin, S.H.; Gal, Y.S. Macromolecules 2002, 35, 7532. (c) Jin, Y.; Kim, K.; Park, S. H.; Song, S.; Kim, J.; Jung, J.; Lee, K.; Suh, H. Macromolecules 2007, 40, 6799. 19 Jiang, B. W.; Jones Jr., W. E. Macromolecules 1997, 30, 5575. 20 Su, W.-F.; Yeh, K.-M.; Chen, Y. J. Polym. Sci., A, Polym. Chem. 2007, 45, 4377. 21 Naik, P. U.; McManus G. J.; Zaworotko, M. J. ; Singer, R. D. Dalton Trans. 2008, 4834. 22 Hibert, M.; Solladie, G. J. Org. Chem. 1980, 45, 4496. 23 Wang, W.; Li, T.; Attardo, G. J. Org. Chem. 1997, 62, 6598. 24 Schwalm, T.; Wiesecke, J.; Immel, S.; Rehahn, M. Macromolecules 2007, 40, 8842 25 (a) Hsieh, B. R.; Yu, Y.; Van Laeken, A. C.; Lee, H. Macromolecules 1997, 30, 8094. (b) Hsieh, B. R.; Yu, Y.; Forsythe, E. W.; Schaaf, G. M.; Feld, W. A. J. Am. Chem. Soc. 1998, 120, 231. (c) Schwalm, T.; Rehahn, M. Macromol. Rapid Commun. 2008, 29, 33 (d) Parekh, B. P.; Tangonan, A. A.; Newaz, S. S.; Sanduja, S. K.; Ashraf, A. Q.; Krishnamoorti, R.; Lee, T. R.  185  Macromolecules 2004, 37, 8883. 26 Cattoen, X.; Sole, S.; Bertrand, G. J. Org. Chem. 2003, 68, 911. 27 Kim, D.-H.; Choi, M. J.; Chang, S.-K. Bull. Kor. Chem. Soc. 2000, 21, 145.  186 Chapter 6  Conclusions and Future Directions  6.1 Overview  This thesis has described the synthesis and characterization of new [2+2] Schiff-base macrocycles and molecular isosceles triangles. These Schiff-base macrocycles are conjugated rings possessing a crown ether-like central cavity and N2O2 binding sites. The abilities of these macrocycles to assemble into host-guest complexes upon addition of organic cations have been investigated. 1H NMR spectra of host-guest complexes showed peak shifts compared to the spectra of both host and guest molecules. ROE couplings were observed between host and guest in 2D-ROESY NMR spectra of the inclusion complexes. MALDI-TOF mass spectra of the complexes exhibited peaks assigned to the complexes. A new kind of donor-acceptor-donor 3-in-1 complex was found in solution by combining macrocycle 46, CBPQT4+ and TTF. It was also discovered that naphthalene-based Schiff-base macrocycles form lyotropic liquid crystals in chloroform and 1,2-dichloroethane in room temperature. Interestingly, lyotropic liquid crystalline phases were also observed in a solution of host-guest complex of naphthalene-base macrocycle and cetylpyridinium. These lyotropic mesophases are believed to be based on a bilayer structure. The recognition of organic cations by Schiff-base macrocycles has never been reported before, and the work presented in this thesis has showed that this is an area of investigation worth further development.  187  6.2 [2+2] Schiff-base Macrocycles  Through the reaction of 39 with diformyl compound 25, [2+2] Schiff-base macrocycles were synthesized in decent yield (20-30%). Semi-empirical calculations showed that this macrocycle is not flat, but instead is in a cone-like shape. 1H-NMR spectroscopy, 2D-ROESY spectroscopy and mass spectrometry showed that organic cations, such as pyridinium, ammonium and paraquat derivatives can be bound inside the macrocycles. 1H NMR titration indicated the association constants between macrocycles and organic cations are pretty high (103-105 M-1). Job plots confirmed the stoichiometry of the host-guest complex is 1:1. It may be possible to further extend the host-guest interaction to the synthesis of rotaxanes. I have initiated this work by synthesizing pseudorotaxanes via templation methods. The [2+2] macrocycles described in Chapter 2 required harsh conditions for their synthesis - refluxing in CHCl3/MeCN with catalyst. In a further study, I found that without catalyst and at room temperature, it is difficult for the reaction between 39 and 25 to obtain a cyclized product (Scheme 6.1). From 1H NMR spectroscopy and MALDI-TOF mass spectrometry, more than 70% of the product is the 1:1 compound 85, while the cyclized product 35 is obtained in less than 5%. The yield of cyclized product is not substantially increased by a longer reaction time. However, by addition of 1.5 equivalents of a doubly-charged cationic dumbbell-shaped molecule 87, the reaction of 39 and 25 under the same conditions, gave mostly the cyclolized product (Scheme 6.2). This result indicates that the cyclization reaction went much faster through templation with dicationic compound 87. The MALDI-TOF mass spectrum showed a peak at  188 3602.6 a.m.u. is present, assigned to a rotaxane or pseudorotaxane of the macrocycle and 87.  Scheme 6.1 Reaction of 39 and 25 in room temperature without catalyst.  HO OH N N NH2 NH2 H11C5O H11C5O OC5H11 OC5H11 + OH OH O O CHCl3 / MeCN room temperature HO OH N N NH2 N H11C5O H11C5O OC5H11 OC5H11 HO HO O HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 HO HO O OH OH O + 85 60 86 35 + HO OH N N NH2 N H11C5O H11C5O OC5H11 OC5H11 HO HO N N OHHO N NH2 OC5H11 OC5H11H11C5O H11C5O + HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 HO HO N N OHHO N N OC5H11 OC5H11H11C5O H11C5O OH OH 39 25      189 Scheme 6.2 Synthesis of [2+2] macrocycle by templation methods. HO OH N N NH2 NH2 H11C5O H11C5O OC5H11 OC5H11 + OH OH O O + 84 84 HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 HO HO N N OHHO N N OC5H11 OC5H11H11C5O H11C5O OH OH O O N N O O OO PF6- PF6 - 87 87   To test whether this product is a rotaxane or only a pseudorotaxane, Ni2+ was added to the product solution. Ni2+ can coordinate inside the N2O2 pockets so that the macrocycle can be “locked” into a less flexible structure with a smaller cavity. After adding the Ni2+, MALDI-TOF mass spectrum showed the dicationic dumbbell-shape molecule 87 was removed from the cavity of the macrocycle. This result indicates that the product obtained through templation is a pseudorotaxane instead of a rotaxane. As additional proof that the product is a pseudorotaxane, addition of 0.1 equivalents of 87 to the mixture of 39 and 25 gave mostly the cyclized product. This result indicated that the dicationic compound is behaving as a catalytic template for macrocycle formation. It was surprising that the product is a pseudorotaxane rather than a rotaxane.  The large tris(t-butylphenyl)methyl groups have been used as stoppers on several other rotaxane systems  190 and are one of the largest stoppers known. I expected that this group would be big enough to prevent 87 from slipping off of the macrocycle. Since the cavity of the [2+2] Schiff-base macrocycle is much bigger than normal macrocycles, a larger stopper will be required to form a rotaxane. By designing a larger stopper, a rotaxane may be obtained by the templation method. In addition to the preparation of rotaxanes, the [2+2] macrocycle could be used to synthesize catenanes. 1  The key point for preparation of catenanes is to synthesize suitable cationic macrocycles. If a macrocycle such as 88 is combined with compounds 39 and 25, a [2]catenane may be obtained via Schiff-base reaction, as shown in Scheme 6.3. With similar methods, a [3]catenane could be prepared by combining macrocycle 89 with 2 equivalents of compounds 39 and 25 (Scheme 6.4).  Scheme 6.3 Synthesis of a [2]catenane 88 N PF6- HO OH NN NH2 OC5H11 OC5H11 H11C5O H11C5O H + NH2 + OH OH O O 39 25    191  Scheme 6.4  Synthesis of a [3]catenane 89 39 25 N N PF6- PF6- HO OH NN NH2 OC5H11 OC5H11 H11C5O H11C5O H + NH2 + OH OH O O 2 2   6.3 Molecular Isosceles Triangles   Through a cascade of Schiff-base condensations, new molecular isosceles triangles were synthesized. Although there are many literature reports of the synthesis of molecular triangles, the isosceles triangle-shaped macrocycles are rare. This macrocycle proved to be an efficient supramolecular receptor. Unlike the other Schiff-base macrocycles I investigated, this macrocycle possesses two different kinds of N2O2 pockets. When metallated, these macrocycles may exhibit interesting properties due to the different surroundings of the metal centres. As the macrocycle was synthesized through two separate steps, it may be possible to obtain  192 a metallated macrocycle that incorporates two different metals (Scheme 6.5).  Scheme 6.5 Proposed synthesis of metallated macrocycles with two different metals.             O O N N N N H11C5O H11C5O OC5H11 OC5H11 O HO O O OH O Ni Ni H25C12O OC12H25 H2N NH2 O O N N N N H11C5O H11C5O OC5H11 OC5H11 O HO N O OH N Ni Ni H25C12O OC12H25 Zn(OAC)2 HO OH N N N N H11C5O H11C5O OC5H11 OC5H11 HO HO O OH OH O + 2 Ni(OAc)2 O O N N N N H11C5O H11C5O OC5H11 OC5H1 1 O O N O O N Ni Ni Zn H25C12O OC12H25 81 90 9192  6.4 Naphthalene-based [2+2] Schiff-base Macrocycles  Naphthalene-based [2+2] Schiff-base macrocycles were obtained by condensation of compounds 39 and 28. Like the other Schiff-base macrocycles, the naphthalene-based [2+2] macrocycle is also a good supramolecular receptor for organic cations. This macrocycle forms lyotropic liquid crystalline phases in some organic solvents. Interestingly, unlike other  193 disc-shaped macrocycles that form column phases, a lamellar phase was observed for the naphthalene-base macrocycle. The interesting property can be attributed to the unusual conformation and structure of this macrocycle. Four ketimine phenyl rings prevent the macrocycle from stacking on top of each other and the naphthalene moieties facilitate π-π interactions between two macrocycles to form bilayer structures. I also found the complex of the macrocycle with cetylpyridinium can give a lyotropic liquid crystalline phase, which I think is the highlight of this thesis. From the oily streak texture and calamitic lyotropic nematic texture that observed by POM, the liquid crystal formed by host-guest complex is based on bilayer structure as well. Liquid crystals formed by macrocylic hosts and organic guests (e.g., cetylpyridinium) have never been reported in the literature. This may be worthy of further exploration and may give rise to a new family of supramolecular liquid crystals.             194  6.5 References   1 Liu,Y; Vignon, S. A.; Zhang, X.; Bonvallet, P. A.; Khan, S. I.; Houk, K. N.; Stoddart, J. F. J. Org. Chem. 2005, 70, 9334.  195 Appendices  Appendix A  Job Plots (Continuous variation method)   A1 Experiment procedure for Job plots   The stoichiometry of each host-guest complex was determined by Job’s methods of continuous variations. Host and guest compounds were dissolved in deuterated solvent in NMR tubes, in which the total concentration of host and guest was kept constant. Normally, the molar fraction of host and guest in the resulting solution in NMR tubes varied from 0.1 to 0.9. The changes in chemical shifts (Δδ) were multiplied by molar fraction and plotted against molar fraction to obtain the Job plot.   A2 Job Plots mole fraction of macrocycle 1 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 (a) mole fraction of macrocycle 2 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .02 .04 .06 .08 .10 (b) mole fraction f macrocy le 35 mole fraction of macro ycle 46 Figure A1. Job plots of (a) 48+ ⊂ 35 and (b) 48+ ⊂ 41 (400 MHz, CDCl3, 298 K).        196   mole fraction of macrocycle 35 mole fraction of macrocycle 46           Figure A2. (a) Job plot of macrocycle 35 with 512+ in CDCl3/CD3OD (3:1). (b) Job plot of macrocycle 41 with 512+ in CDCl3/CD3OD (3:1).      mole fraction of macrocycle 1 0.0 .2 .4 .6 .8 1.0 Δδ  X m ol e fra ct io n 0.00 .02 .04 .06 .08 .10(a) mole fraction of macrocycle 2 0.0 .2 .4 .6 .8 1.0 Δδ  x m ol e fra ct io m 0.000 .005 .010 .015 .020 .025 .030(b) Δδ  X m ol e fra ct io n Δδ  x m ol e fra ct io m mole fraction of macrocycle 35 mole fractio f macrocycle 46  Figure A3. (a) Job plot of macrocycle 35 with cetyltrimethylammonium bromide (49+·Br-)in CDCl3. (b) Job plot of macrocycle 41 with 49+·Br- in CDCl3.            197               Figure A4. (a) Job plot of macrocycle 35 with tetrabutylammonium bromide (50+·Br-) in CDCl3. (b) Job plot of macrocycle 41 with 50+·Br- in CDCl3.       mole fraction of 11+Cl- 0.0 .2 .4 .6 .8 1.0 Δδ  x  m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 mole fraction of 10+Cl- mole fraction of 11+Cl- 0.0 .2 .4 .6 .8 1.0 Δδ  x  m ol e fra ct io n 0.00 .02 .04 .06 .08 .10 .12 .14 mole fraction of 10+Cl-mole fraction of 48+ mole fraction of 48+ (a) (b)  Figure A5. (a) Job plot of macrocycle 58 with 48+·Br- in CDCl3. (b) Job plot of macrocycle 59 with 48+·Br- in CDCl3.      mole fraction of macrocycle 1 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.000 .002 .004 .006 .008 .010 .012 .014 .016(a) (b) mole fraction of macrocycle 2 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.000 .002 .004 .006 .008 .010 .012 .014 .016 Δδ  x m ol e fra ct io n Δδ  x m ol e fra ct io n mole fraction acro ycle 35 mole fraction of cro ycle 46  198 mole fraction 0.0 .2 .4 .6 .8 1.0 Δδ  x m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 .30 mole fraction of macrocycle 66 mole fraction 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 Δδ  x m ol e fra ct io n 0.00 .05 .10 .15 .20 .25 .30 .35 mole  fraction of macrocycle 66 Figure A6. (a) Job plot of macrocycle 66 with 48+·Br- in CDCl3. (b) Job plot of macrocycle 68 with 48+·Br- in CDCl3.                mole fraction 0.0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 0.00 .01 .02 .03 .04 n  fr ac tio x m ol e Δδ  Mole fraction of macrocycle 66 Figure A7. Job plot of macrocycle 66 with 49+·Br- in CDCl3.            199 Appendix B  Titration curve and stacked 1H NMR spectra  B1 Experiment procedure for NMR titrations  The host macrocycle was dissolved in an appropriate amount of deuterated solvent in a vial. 400 μL of the resulting solution was added into an NMR tube. The guest compound was dissolved in the host solution in the vial to form a host-guest solution. By microsyringe, the host-guest solution was added, in calculated amount, into the NMR tube which originally contains 400 μL host solution. The 1H NMR experiments were continued until no significant change in chemical shift was observed in successive 1H NMR spectra. Binding constant was calculated by nonlinear curve fitting methods for the guest-induced chemical shifts of the selected peaks.                             200   B2 Titration curve and stacked 1H NMR spectra  equivalent of cetylpyridinium chloride 0 2 4 6 8 1  0 ch em ic al  s hi ft (p pm ) 13.0 13.2 13.4 13.6 13.8(a)                                Figure B1. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 35 with cetylpyridinium chloride 48+·Cl- (400 MHz, CDCl3, 298 K).     201   equivalent of cetyltrimethylammonium bromide 0 2 4 6 8 1 (a)  12.95 13.00 13.05 13.10 13.15 13.20 0   ch em ic al  s hi ft (p pm )             (b)                   Figure B2. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 35 with cetyltrimethylammonium bromide 49+·Br- (400 MHz, CDCl3, 298 K).    202  equivalent of tetrabutylammonium bromide 0 2 4 6 8 1 (a)  12.9 13.0 13.1 13.2 13.3 0   ch em ic al  s hi ft (p pm )              (b)                  Figure B3. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 35 with tetrabutylammonium bromide 50+·Br- (400 MHz, CDCl3, 298 K).     203    equivalent of methyl viologen 0 2 4 6 8 1 (a) 0 ch em ic al  s hi ft (p pm ) 4.8 5.0 5.2 5.4 5.6 5.8 6.0 6.2 6.4                (b)                   Figure B4. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 35 with methyl viologen dichloride 512+·2Cl- in CDCl3/CD3OD (3 : 1) (400 MHz, 298 K).     204   equivalent of cetylpyridinium chloride 0 2 4 6 8 1 (a)  13.9 14.0 14.1 14.2 14.3 14.4 14.5 14.6 0   ch em ic al  s hi ft (p pm )              (b)                  Figure B5. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 41 with cetylpyridinium chloride 48+·Cl- (400 MHz, CDCl3, 298 K).    205  equivalent of cetyltrimethylammonium bromide 0 2 4 6 8 1 (a)  13.9 14.0 14.1 14.2 14.3 14.4 14.5 14.6 0   ch em ic al  s hi ft (p pm )              (b)                   Figure B6. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 41 with cetyltrimethylammonium bromide 49+·Br- (400 MHz, CDCl3, 298 K).    206   equivalent of tetrabutylammonium bromide 0 2 4 6 8 1 (a)  13.90 13.95 14.00 14.05 14.10 14.15 14.20 0   ch em ic al  s hi ft (p pm )             (b)                   Figure B7. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 41 with tetrabutylammonium bromide 50+·Br- (400 MHz, CDCl3, 298 K).    207   (a) equivalent of methyl viologen 0 1 2 3 4 5 6 ch em ic al  s hi ft (p pm ) 8.2 8.3 8.4 8.5 8.6 8.7 8.8   (b)                   Figure B8. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 41 with methyl viologen dichloride 512+·2Cl- in CDCl3/CD3OD (3:1) (400 MHz, 298 K).   208   (a) equivalent of CBPQT4+ 0.0 .5 1.0 1.5 2.0 2.5   14.2 14.3 14.4 14.5 14.6 14.7 14.8   ch em ic al  s hi ft (p pm )              (b)                  Figure B9. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 46 with CBPQT4+ (PF6)4 in CDCl3/CD3CN (1:1) (400 MHz, 298 K).   209    equivalent of cetylpyridinium chloride 0.0 .5 1.0 1.5 2.0 2.5 chem ical shift (ppm ) 13.4 13.6 13.8 14.0 14.2 (a) (b) Equivalents of ce ylpyridinium chloride 11+Cl-Equivalents of cetylpyridinium 10+Cl- chem ical shift (ppm ) e i l t  f t l i i i chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm ) chem ical shift (ppm )                                Figure B10. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 58 with cetylpyridinium chloride 48+·Cl- (400 MHz, CDCl3, 298K).         210                                    equivalents of 7+Br- 0 2 4 6 8 10 chem ical shift 13.5 13.6 13.7 13.8 13.9 14.0(a) (b) Equivalents of cetyltrimethylammonium bromide 12+Br-Equivalents of cetyltrimethylammonium bromide 11+Br- chem ical shift e i l t  f chem ical shift chem ical shift chem ical shift chem ical shift chem ical shift chem ical shift chem ical shift chem ical shift  Figure B11. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 58 with cetyltrimethylammonium bromide 49+·Br- (400 MHz, CDCl3, 298K).       211                                    equivalents of 8+Br- 0 2 4 6 8 10 ch em ic al  s hi ft 13.50 13.55 13.60 13.65 13.70 (a) (b) Equivalents of tetraethylammonium bromide 13+Br- equivalents of tetraethylammonium bromide 12+Br- ch em ic al  s hi ft  Figure B12. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 58 with tetraethylammonium bromide (400 MHz, CDCl3, 298K).       212      equivalents of trtabutylammonium bromide 14+Br- 0 2 4 6 8 10 ch em ic al  s hi ft 13.460 13.465 13.470 13.475 13.480(a) (b) equivalents of tetrabutyla monium bromide 13+Br- ch em ic al  s hi ft                                   Figure B13. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 58 with tetrabutylammonium chloride (400 MHz, CDCl3, 298K).    213     equivalents of cetylpyridinium chloride 11+Cl- 0.0 .2 .4 .6 .8 1.0 1.2 1.4 1.6 1.8 2.0 ch em ic al  s hi ft 15.65 15.70 15.75 15.80 15.85 15.90 15.95 16.00 16.05(a) (b) ch em ic al  s hi ft equivalents of cetylpyridinium chloride 10+Cl-                                    Figure B14. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 59 with tetrabutylammonium chloride 48+·Cl- (400 MHz, CDCl3, 298K).    214  equivalents of cetyltrimethylammonium bromide 12+Br- 0 2 4 6 8                                       10 ch em ic al  s hi ft 15.16 15.18 15.20 15.22 15.24 15.26 15.28 15.30 15.32(a) (b) ch em ic al  s hi ft equivalents of cetyltrimethylammonium bromide 11 Br  Figure B15. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 59 with cetyltrimethylammonium bromide 49+·Br- (400 MHz, CDCl3, 298K).   215  (a) 14.8 14.9 15.0 15.1 15.2   Figure B16. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 66 with cetylpyridinium chloride 48+·Cl- (400 MHz, CDCl3, 298K).     equivalent of cetylpyridinium chloride ch em ic al  s hi ft (p pm ) 0.0 .5 1.0 1.5 2.0 2.5 3.0 3.5 (b)  216   equivalent of 1-dodecyl-3-methylpyridinium bromide 0.0 .5 1.0 1.5 2.0 2.5 3.0 3.5 ch em ic al  s hi ft (p pm ) 14.8 14.9 15.0 15.1 15.2 15.3 ch em ic al  s hi ft (p pm ) (a) (b)    Figure B17. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 66 with 1-dedocyl-3-methylpyridinium bromide (400 MHz, CDCl3, 298K).       217   equivalent of cetyltrimethylammonium bromide 0 2 4 6 8 10 ch em ic al  s hi ft (p pm ) 14.55 14.60 14.65 14.70 14.75 ch em ic al  s hi ft (p pm ) (a) (b)   Figure B18. Titration curve (a) and stacked 1H NMR spectra (b) of macrocycle 66 with cetyltrimethylammonium bromide 49+·Br- (400 MHz, CDCl3, 298K).        218

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.24.1-0060358/manifest

Comment

Related Items