Science, Faculty of
Chemistry, Department of
DSpace
UBCV
Tong, Xing
Doctor of Philosophy - PhD
University of British Columbia
Weak interactions, commonly known as secondary bond interactions (SBIs), have received far less attention than their stronger counterparts (i.e., primary bonds, e.g., ionic, metallic, and covalent bonds). The most mainstream perspective is that those interactions are induced by the attraction between partially positive and partially negative areas on molecular surfaces. This electrostatics-driven model has been widely accepted as it is straightforward, intuitive, and widely applicable; however, more and more computational and experimental discoveries have thrown this “simple and practical” theory into question. Other quantum chemical effects like charge transfer cannot be ignored if a generalized picture of weak interactions is required. Due to the relatively weak bond strengths, it is often difficult to study weak interactions exclusively and accurately. With synchrotron X-ray absorption spectroscopy (XAS) in combination with different computational methods, the nature of two common weak interactions (i.e., halogen bonding XB and chalcogen bonding ChB) has been comprehensively investigated. To begin with, two types of model systems (i.e., hypervalent halogen salts and bis-triazole-pyridinium series) were chosen to study the degree of charge transfer in XB and ChB. These studies have given evidence for a substantial degree of covalent contribution in both XB and ChB interactions. The relevance of such interactions in modulating chemical processes has also been explored. For example, the significance of the charge transfer component in XB was confirmed in a catalyzed Ritter-like process (carbon-halogen bond cleavage). We have further demonstrated the important role of ChB in processes ranging from petroleum-coke modification to pharmaceutical drug synthesis. The obtained data has shown that both XBs and ChBs should be considered as partially covalent interactions and the covalent contributions can be tuned by the properties of involved electron donor/acceptor pairs. Those results are intended for a more rational design of the weak-interaction-assisted systems in many fields, such as catalysis, synthesis, anion recognition, and molecular electronics.
DEFINING THE ROLE OF PARTIALLY COVALENT WEAK INTERACTIONS IN CHEMICAL REACTIONS by Xing Tong B.E., South China University of Technology, 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2022 © Xing Tong, 2022 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Defining the Role of Partially Covalent Weak Interactions in Chemical Reactions submitted by Xing Tong in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Examining Committee: Dr. Suzana Straus, Professor, Department of Chemistry, UBC Co-supervisor Dr. Pierre Kennepohl, Professor, Department of Chemistry, UBC/University of Calgary Co-supervisor Dr. Chris Orvig, Professor, Department of Chemistry, UBC Supervisory Committee Member Dr. Grenfell Patey, Professor, Department of Chemistry, UBC University Examiner Dr. Mark Thachuk, Associate Professor, Department of Chemistry, UBC University Examiner Additional Supervisory Committee Members: Dr. Curtis Berlinguette, Professor, Department of Chemistry, UBC Supervisory Committee Member iii Abstract Weak interactions, commonly known as secondary bond interactions (SBIs), have received far less attention than their stronger counterparts (i.e., primary bonds, e.g., ionic, metallic, and covalent bonds). The most mainstream perspective is that those interactions are induced by the attraction between partially positive and partially negative areas on molecular surfaces. This electrostatics-driven model has been widely accepted as it is straightforward, intuitive, and widely applicable; however, more and more computational and experimental discoveries have thrown this “simple and practical” theory into question. Other quantum chemical effects like charge transfer cannot be ignored if a generalized picture of weak interactions is required. Due to the relatively weak bond strengths, it is often difficult to study weak interactions exclusively and accurately. With synchrotron X-ray absorption spectroscopy (XAS) in combination with different computational methods, the nature of two common weak interactions (i.e., halogen bonding XB and chalcogen bonding ChB) has been comprehensively investigated. To begin with, two types of model systems (i.e., hypervalent halogen salts and bis-triazole-pyridinium series) were chosen to study the degree of charge transfer in XB and ChB. These studies have given evidence for a substantial degree of covalent contribution in both XB and ChB interactions. The relevance of such interactions in modulating chemical processes has also been explored. For example, the significance of the charge transfer component in XB was confirmed in a catalyzed Ritter-like process (carbon-halogen bond cleavage). We have further demonstrated the important role of ChB in processes ranging from petroleum-coke modification to pharmaceutical drug synthesis. The obtained data has shown that both XBs and ChBs should be considered as partially covalent interactions and the covalent contributions can be tuned by the properties of involved electron donor/acceptor pairs. Those results are intended for a more rational design of the iv weak-interaction-assisted systems in many fields, such as catalysis, synthesis, anion recognition, and molecular electronics. v Lay Summary Weak interactions are ubiquitous in chemistry and biology. These forces are generally involved in the process of dissolution in solvents, the orientation of reacting molecules, or the junctions of building blocks. Such common interactions are usually ignored and rarely characterized due to their instability. However, they can sometimes play a vital role in important chemical processes. Competitive interactions may lead to the formation of different products; undesired interactions can totally inhibit the expected reactions; the alteration of entangled weak interactions would also change the reactive sites on the chemicals. Therefore, a deeper understanding of the nature of weak interactions is necessary. Herein, we have shown a better picture of weak interactions and their significance in petroleum-coke modification and pharmaceutical drug synthesis. This allows for a more appropriate utilization of such interactions. vi Preface Chapter 2 The work in Chapter 2 was conducted by the author under the supervision of Prof. Pierre Kennepohl. The author was responsible for the project design, chemical synthesis, spectroscopic characterization, computational work, data analysis, and result interpretation. Kristof Altus from the Department of Chemistry at the University of British Columbia (UBC) has provided useful suggestions and assistance in the synthesis of bromonium and chloronium salts. Single crystal X-ray diffraction (XRD) experiments and data reduction were carried out by Dr. Benjamin Gelfand from the Department of Chemistry at the University of Calgary. Chapter 3 The project in Chapter 3 was carried out in collaboration with Prof. Paul Beer and Dr. Andrew Docker at the University of Oxford. The bis-triazole-pyridinium salts, in combination with their single crystal XRD and kinetic results, were provided by Dr. Andrew Docker. The XAS experiments, computational data analysis, and result interpretation were done by the author. Chapter 4 The project in Chapter 4 was conducted in collaboration with Prof. Stefan M. Huber at Ruhr-Universität Bochum. The halogen bonding activators were provided by the Huber group. The author performed the XAS tests, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, mechanistic study, and written work. Chapter 5 Chapter 5 consists of two parts, including the petroleum coke modification and the reaction mechanism of benzisothiazole conversions. vii The petroleum coke (or petcoke) modification project was conducted in collaboration with Prof. Josephine Hill and Dr. Qing Huang at Schulich School of Engineering, University of Calgary. The petcoke treatments using nitric acid under different experimental conditions, in combination with the sample characterizations, were carried out by Dr. Qing Huang. The author was responsible for the DFT calculations, result analysis, and mechanistic investigations. The work in section 5.2 is based on a publication in The Journal of Organic Chemistry: Zheng Sonia Lin, Xing Tong, Brian Patrick, Pierre Kennepohl, and David S. Grierson. Reaction of 3-Cl/OMe-Substituted 5-Nitrobenzisothiazoles with Hydrazine: Structural and Computational Evidence for Rearrangement Pathways Implicating Intramolecular Formation of Pivotal Meisenheimer Complexes. J. Org. Chem. 2021, 86, 6381-6389. The manuscript was written in collaboration with Prof. David S. Grierson and Dr. Zheng Sonia Lin in the Faculty of Pharmaceutical Sciences, UBC. Dr. Zheng Sonia Lin has conducted the synthesis and relevant characterizations. The author has performed the mechanistic study and DFT calculations. Appendix The work in Appendix A was designed and conducted by the author with the assistance of two visiting students Kerstin Rickmeyer and Usman Jamshed in the Kennepohl lab. The work in Appendix B was planned and performed by the author under the supervision of Prof. Pierre Kennepohl. Single crystal X-ray diffraction experiments and data reduction were carried out by Dr. Brian Patrick from the Department of Chemistry at UBC. viii Table of Contents Abstract ......................................................................................................................................... iii Lay Summary .................................................................................................................................v Preface ........................................................................................................................................... vi Table of Contents ....................................................................................................................... viii List of Tables .............................................................................................................................. xiii List of Figures ...............................................................................................................................xv List of Schemes ......................................................................................................................... xxiv List of Symbols ....................................................................................................................... xxviii List of Abbreviations ............................................................................................................... xxix Acknowledgements ................................................................................................................ xxxiii Dedication .................................................................................................................................xxxv Chapter 1: Introduction ................................................................................................................1 1.1 Halogen Bonding ............................................................................................................ 1 1.1.1 “Dominant Role”: Electrostatics? ........................................................................... 4 1.1.2 The More, the Better? ............................................................................................. 6 1.1.2.1 “Counter-Intuitive” Computational Models ....................................................... 6 1.1.2.2 Experimental and Spectroscopic Findings ........................................................ 10 1.1.3 Different Scenarios, Different Focuses ................................................................. 14 1.2 Chalcogen Bonding ....................................................................................................... 20 1.2.1 Comparison of Chalcogen Bonding and Halogen Bonding .................................. 20 1.2.1.1 Similarity........................................................................................................... 20 ix 1.2.1.2 Differences ........................................................................................................ 21 1.3 Thesis Aim .................................................................................................................... 22 Chapter 2: Probing the Nature of Halogen Bonding in Ionic Systems ...................................25 2.1 Physical Properties of Hypervalent Halogen (III) Complexes ..................................... 29 2.1.1 Solubility ............................................................................................................... 29 2.1.2 Stability ................................................................................................................. 30 2.2 Crystal Structures of Hypervalent Halogen (III) Complexes ....................................... 35 2.2.1 Crystal Structures of DPI Series ........................................................................... 35 2.2.2 Crystal Structure of DPEI Series .......................................................................... 40 2.2.3 Similarity and Difference between DPI and DPEI Series .................................... 44 2.2.4 Crystal Structures of DPEBr Series ...................................................................... 46 2.3 Electronic Structures of Hypervalent Halogen (III) Complexes ................................... 48 2.3.1 NMR Results ......................................................................................................... 48 2.3.2 XAS Analysis ....................................................................................................... 51 2.3.2.1 Theories of XAS Techniques ............................................................................ 51 2.3.2.2 XAS Results ...................................................................................................... 54 2.3.3 Computational Investigations ............................................................................... 57 2.3.3.1 DFT Calculations to Find Out the Representative Unit .................................... 57 2.3.3.2 TD-DFT Simulations to Probe the Covalent Contributions ............................. 61 2.3.3.3 Charge Decomposition Analysis to Study the Covalent Contribution ............. 64 2.4 Conclusion and Future Prospects .................................................................................. 65 2.5 Methods......................................................................................................................... 66 2.5.1 Sample Synthesis .................................................................................................. 66 x 2.5.2 XAS Experiment Setup ......................................................................................... 81 2.5.3 Computational Methods ........................................................................................ 81 Chapter 3: Probing the Nature of Chalcogen Bonding in Ionic Systems ...............................83 3.1 Comparison of Electronic Structures among HB, XB, and ChB .................................. 84 3.2 Comparison of Electronic Structures among Different ChB Systems .......................... 87 3.3 Conclusion .................................................................................................................... 91 3.4 Methods......................................................................................................................... 91 Chapter 4: Exploring the Function of XB in Halogen-Containing Chemical Reactions ......93 4.1 Background ................................................................................................................... 93 4.2 Investigations on Mechanistic Pathways ...................................................................... 95 4.2.1 Probing the Reaction Mechanism using XAS Techniques ................................... 95 4.2.2 Probing the Reaction Mechanism using DFT Calculations .................................. 99 4.3 The Effects of Different Activators ............................................................................ 101 4.3.1 Comparing Different Activators using XAS and TD-DFT Methods .................. 101 4.3.2 Comparing Different Activators by DFT Calculations ....................................... 106 4.4 Conclusion .................................................................................................................. 108 4.5 Methods....................................................................................................................... 108 Chapter 5: From XB to ChB: Chalcogen-Containing Chemical Reactions .........................111 5.1 Nitric Acid Functionalization of the Inherent Sulfur in Petcoke ................................ 111 5.1.1 Background ......................................................................................................... 111 5.1.2 Experimental and Computational Studies of Sulfur Conversion Process ........... 111 5.1.2.1 Oxidation Reactions: from DBT to DBTO3 .................................................... 113 5.1.2.2 Hydrolysis Reactions: from DBTO3 to HBPS ................................................ 119 xi 5.1.2.3 Loss of Sulfur .................................................................................................. 120 5.1.3 Methods............................................................................................................... 122 5.2 Reaction of 3‑Cl/OMe-Substituted 5‑Nitrobenzisothiazoles and Hydrazine .............. 124 5.2.1 Background ......................................................................................................... 124 5.2.2 Computational Studies of the Proposed Reaction Mechanism ........................... 126 5.2.2.1 The Reaction of 5-Nitro-3-Methoxybenzisothiazole 6a ................................. 127 5.2.2.2 The Reaction of 3-Chloro-5-Nitrobenzisothiazole 6b .................................... 133 5.2.3 Methods............................................................................................................... 139 5.3 Conclusion .................................................................................................................. 140 Chapter 6: Conclusion and Future Directions ........................................................................142 6.1 Thesis Summary .......................................................................................................... 142 6.2 Future Directions ........................................................................................................ 143 Bibliography ...............................................................................................................................147 Appendices ..................................................................................................................................158 Appendix A Investigation on Halogen Bonding in Substituted 1-Methylpyridinium Systems with One Interaction Site ........................................................................................................ 158 A.1 Background ............................................................................................................. 158 A.2 Results - Halide Ion as XB Donor .......................................................................... 159 A.3 Results - TEMPO as XB Donor .............................................................................. 165 A.4 Comparison of Results from Two Different Donors .............................................. 168 A.5 Methodology ........................................................................................................... 169 Appendix B Investigation on Halogen Bonding in Substituted 1-Methylpyridinium Systems with Two Interaction Sites ...................................................................................................... 170 xii B.1 Background ............................................................................................................. 170 B.2 Results and Discussion ........................................................................................... 171 B.3 Conclusion and Reflections .................................................................................... 173 Appendix C Supplementary Information of Chapter 2 ........................................................... 174 C.1 Single Crystal X-Ray Diffraction Data ................................................................... 174 C.2 13C NMR spectra ..................................................................................................... 182 xiii List of Tables Table 2.1 The important parameters of the formed XBs in DPI series. ........................................ 37 Table 2.2 Comparison between major and minor disorders in four DPI complexes .................... 40 Table 2.3 Important parameters of the formed XBs in DPEI series. ............................................ 41 Table 2.4 Important parameters of the formed XBs in DPEBr series. ......................................... 47 Table 2.5 A summary of fitting results in DPI-Cl, DPEI-Cl, and DPEBr-Cl systems. ................ 56 Table 2.6 A summary of structural information of DPI-Cl system generated from XRD and DFT results. ........................................................................................................................................... 58 Table 2.7 A summary of structural information of DPI-Br system generated from XRD and DFT results. ........................................................................................................................................... 58 Table 2.8 A summary of structural information of DPI-I system generated from XRD and DFT results. ........................................................................................................................................... 58 Table 2.9 A summary of structural information of DPEI-Cl system generated from XRD and DFT results.................................................................................................................................... 59 Table 2.10 A summary of structural information of DPEI-Br system generated from XRD and DFT results.................................................................................................................................... 60 Table 2.11 A summary of structural information of DPEI-I system generated from XRD and DFT results.................................................................................................................................... 60 Table 2.12 Calculated ∆Gf 0 and spectroscopically resolved results in the studied systems ........ 61 Table 2.13 Comparison of total charge donation from CDA analysis and XAS fitting ............... 65 Table 3.1 Spectroscopically resolved pre-edge intensities and the corresponding % charge donation from chloride donor. ...................................................................................................... 85 xiv Table 3.2 Spectroscopically resolved pre-edge intensities and the corresponding % charge donation from chloride donor. ...................................................................................................... 89 Table 4.1 Experimentally obtained pre-edge intensities ............................................................. 104 xv List of Figures Figure 1.1 A cartoon showing the debates between “electrostatic team” and “covalency team”. The XB pair (CH3Br and Cl-) is taken as an example here. The molecular orbital diagram above “covalency team” shows the main idea of the covalency-based theory, where electrons are donated from the nonbonding orbital of Cl- (nCl) to the antibonding orbital of the C−Br bond (σ*C−Br). The scheme above “electrostatic team” depicts the σ hole on the extension of C−Br bond, which interacts with the negatively charged Cl-. .................................................................. 3 Figure 1.2 Two kinds of frameworks in the halogen-involved crystals (top); s2px2py2pz1 configuration in which the s orbital is omitted (bottom). ............................................................... 5 Figure 1.3 Computed electrostatic potential on the 0.001 au molecular surface of F–Cl. The chlorine is in the foreground. Color ranges, in kcal/mol, are as follows: red greater than 20; yellow from 10 to 20; green from 0 to 10; blue less than 0 (negative). The position of the VS,max on the chlorine is denoted by a black hemisphere; its value is 39.9 kcal/mol. Reprinted by permission from [Springer Nature Customer Service Centre GmbH]: [Springer Nature] [Theoretical Chemistry Accounts] [Politzer, P., Murray, J.S. Halogen bonding and beyond: factors influencing the nature of CN–R and SiN–R complexes with F–Cl and Cl2 . Theor Chem Acc 131, 1114 (2012). https://doi.org/10.1007/s00214-012-1114-1, [Copyright © 2012] ............. 7 Figure 1.4 Proposed modes in CF3I ∙∙∙ F- and C(NO2)3I ∙∙∙ F- adducts, in which the purple atoms are iodine atoms, the green atoms are fluorine atoms, the blue atoms are nitrogen atoms, the grey ones are carbon atoms, the red ones are oxygen atoms, the dash line represents the XB interaction (top). Schemes for σ- and π-type interactions (bottom). ............................................. 10 xvi Figure 1.5 (a) A dynamic perspective of I3-; (b) A molecular diagram showing the formation of I3-. .................................................................................................................................................. 12 Figure 1.6 The structure of Dye-X•+(left). The two graphs on the right are reproduced from reference [72] without further changes (© Creative Commons). The experimental XAS spectra (black lines) of Dye-I•+···Cl– (a) and Dye-Br•+···Cl– (b) and the corresponding TD-DFT simulated spectra (calculated using BP86, solid orange lines) are shown along with the relative oscillator strengths of the individual calculated transitions (vertical gray lines). The height of the simulated edge peaks was normalized to the height of the experimental edge peak. The transitions corresponding to pre-edge features were visualized as electron density difference maps (EDDMs) at an isovalue of 0.0004 (inset). The blue lobes represent positive changes in electron density corresponding to the acceptor orbital(s) of the transitions, while the donor orbital was always the chloride 1s (indicated by a negative change in electron density in red and not always visible). In order to highlight the pre-edge features resulting from σ- and π-covalency in Dye−I•+···Cl– and Dye−Br•+···Cl–, truncated versions of the simulated spectra excluding the high energy Cl4p ← Cl1s edge peak transitions were also generated (dotted orange lines). .................. 16 Figure 1.7 Two common modes of activation in XB-assisted catalysis. On the left, the Lewis acid (R−X) is usually the catalyst, while the opposite strategy on the right uses a catalytic Lewis base. The green shaded part is the activator that modulates the reactivity of its partner. ...................... 18 Figure 1.8 Schematic representation of the catalytic SN2 reaction and electron-density flow in each of the transition state structure. This figure has been adapted from reference [75] with the permission from the authors (© Creative Commons). .................................................................. 19 Figure 1.9 Two common modes in ChB-based systems. .............................................................. 21 Figure 2.1 A list of investigated hypervalent halogen (III) compounds. ...................................... 28 xvii Figure 2.2 Top: The solubility comparison of DPEX series in polar solvents; Bottom: The solubility comparison of DPI series in polar solvents. ................................................................. 30 Figure 2.3 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPI-Cl and DPI-Cl after 20 days. ................................................................................................. 31 Figure 2.4 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPEBr-Cl and DPEBr-Cl after 20 days. ....................................................................................... 32 Figure 2.5 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPEBr-Br and DPEBr-Br after 25 days. ...................................................................................... 32 Figure 2.6 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of DPECl-Cl under different conditions. ........................................................................................... 33 Figure 2.7 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of DPECl-Br with decomposition and after solvent wash process. .................................................. 35 Figure 2.8 View of the solid-state molecular structure of each of the species. The grey atoms are carbon atoms; the red ones are oxygen atoms; the purple ones are iodine atoms; the yellow ones stand for sulfur; the brown atoms are bromine; the green ones represent chlorine; the light green atoms are fluorine. ........................................................................................................................ 36 Figure 2.9 The snapshots of some special geometries in the DPI crystal packings. For each scheme, the left picture stands for the front view, and the right picture represents the left view. The π-π interaction lengths are labelled in green beside the green dash line (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). ............................................................... 38 Figure 2.10 Crystal structure of DPI-Cl complex (both major and minor disorders are included). The probability is 50%; The temperature is 173 K. ...................................................................... 39 xviii Figure 2.11 View of the solid-state molecular structure of each of the species. (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). .......................................................... 41 Figure 2.12 2D architectures of DPEI-Cl system. Top view, front view and left view are shown, respectively (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). .......... 43 Figure 2.13 The stacking patterns of DPEI-Cl (left) and DPEI-I (right) (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). ....................................................................... 43 Figure 2.14 The front view of DPEI-Cl and DPEI-I systems (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). ...................................................................................... 43 Figure 2.15 The comparison of the planar structures in DPI-halide and DPEI-halide systems. .. 45 Figure 2.16 View of the solid-state molecular structure of each of the species. (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). .......................................................... 46 Figure 2.17 The stacking patterns of DPEBr-X systems (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). ...................................................................................... 47 Figure 2.18 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPI-X series. ........... 49 Figure 2.19 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEI-X series. ......... 50 Figure 2.20 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEBr-X series. ...... 50 Figure 2.21 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPECl-X series. ...... 51 Figure 2.22 An exemplary XAS graph of tetrabutylammonium bromide solid sample. Spectrum was collected in SSRL. ................................................................................................................. 53 Figure 2.23 A molecular orbital diagram depicts the transitions of the core electrons within different models: (a) electrostatic model only; and (b) with inclusion of charge transfer/covalency. ........................................................................................................................ 54 Figure 2.24 Cl K-edge XAS spectra of DPEI-Cl, DPI-Cl, DPEBr-Cl. ......................................... 55 xix Figure 2.25 An exemplary graph showing how BlueprintXAS fits the given data. ..................... 56 Figure 2.26 A structural snapshot of DPI-Cl system generated from XRD and DFT results (C: grey; Cl: green; I: purple). ............................................................................................................ 57 Figure 2.27 A structural snapshot of DPEI-Cl system generated from XRD and DFT results (C: grey; Cl: green; I: purple). ............................................................................................................ 59 Figure 2.28 TD-DFT simulations of DPEI-Cl and DPEBr-Cl complexes. The inserted pictures in the left graph are visual representations of the important σ*(R-X⟵Cl-) Kohn−Sham acceptor orbitals for each hypervalent salt (isovalue is 0.03 for DPEI-Cl and 0.02 for DPEBr-Cl); the inserted pictures on the right graph are the electron density difference maps for the corresponding transitions (isovalue is set as 0.001). A constant linear shift was applied to the calculated energies to match experimental energies.113 ................................................................................. 62 Figure 2.29 TD-DFT simulation of DPI-Cl complex. The inserted pictures in the left graph are visual representations of the important σ*(R-X⟵Cl-) Kohn−Sham acceptor orbitals for each hypervalent salt (isovalue is 0.02); the inserted pictures in the right graph are the electron density difference maps for the corresponding transitions (isovalue is set as 0.001). A constant linear shift was applied to the calculated energies to match experimental energies.113 .......................... 64 Figure 2.30 Proposed structures with different substituents (left) and with two hypervalent halogens in one cationic moiety (right). ....................................................................................... 66 Figure 3.1 Structures of the bis-triazole-pyridinium-containing model compounds. ................... 84 Figure 3.2 XAS comparison of 1_HB_Cl, 1_XB_Cl and 1_ChB_Cl complexes after normalization and background subtraction. .................................................................................. 85 Figure 3.3 TD-DFT simulated Cl K-edge XAS spectra for 1_XB_Cl and 1_ChB_Cl adducts. A constant linear shift was applied to the calculated energies to match experimental energies.113 . 86 xx Figure 3.4 TD-DFT simulated Cl K-edge XAS spectra for 1_XB_Cl and 1_ChB_Cl adducts. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). .. 87 Figure 3.5 Crystal structures of 1_XB_Cl and 1_ChB_Cl. The numbers labelled on the picture represent the lengths of XB or ChB (unit is Å). The side view of each molecule is attached below (C: grey; H: white; N: light blue; O: red; F: yellow; Cl: green; Te: orange; I: purple). ............... 87 Figure 3.6 XAS comparison of 1_ChB_Cl, 2_ChB_Cl and 3_ChB_Cl complexes after normalization and background subtraction. .................................................................................. 88 Figure 3.7 TD-DFT simulated Cl K-edge XAS spectra for 2_ChB_Cl adduct. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). ............... 90 Figure 3.8 TD-DFT simulated Cl K-edge XAS spectra for 3_ChB_Cl adduct. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). ............... 90 Figure 4.1 The molecular orbital diagram of the covalently-bound bromine in substrate before and after binding with activators. The transitions of interest in Br K-edge XAS are shown in green. ............................................................................................................................................. 96 Figure 4.2 The molecular orbital diagram of the product bromide before and after binding with activators via XB. The transitions of interest in Br K-edge XAS are shown in orange. .............. 97 Figure 4.3 Br K-edge XAS spectra of substrate (a) and TBABr (b) upon addition of 1 equivalent of different activators, respectively. The black line stands for the substrate (a) or TBABr (b) itself. The red line represents the sample with the addition of A1. The blue line shows the sample with the addition of A2. ................................................................................................................ 98 Figure 4.4 The energy profile of three proposed pathways according to DFT calculation (a); Structures of reactant, transition state, intermediate and product in SN1-a pathway (b) (C: grey; H: white; N: blue; Br: dark red; I: purple). ................................................................................. 101 xxi Figure 4.5 XAS spectra of different activator-bromide complexes. The bromide source is TBABr......................................................................................................................................... 102 Figure 4.6 (a) The molecular orbital diagram of the chloride ion involved in an XB with activators. The transitions of interest in Cl K-edge XAS are shown in green and orange, respectively; (b) Cl K-edge XAS spectra of TBACl upon addition of 1 equivalent of different activators, respectively. ............................................................................................................... 103 Figure 4.7 TDDFT simulated Cl K-edge (a) and Br K-edge (b) XAS spectra for A1-X and A3-X. A constant linear shift was applied to the calculated energies to better match experimental K-edge energies.113 The inset figures are the primary σ* R-X ← X- Kohn-Sham acceptor orbitals for A1 and A3. Surface volume for each orbital is plotted for ± 0.03 e/Å3. .......................................... 105 Figure 4.8 Comparison between mono-iodinated and di-iodinated activators. To lower down the computational expenses, A3’ was used as a substitute of A3 in which the octyl group was replaced by a methyl group. ∆G0 represents the Gibbs free energy change after the formation of XBs under the standard conditions (C: grey; H: white; N: blue; Br: dark red; I: purple). ......... 107 Figure 4.9 Comparison among different A3’ variants (C: grey; H: white; N: blue; Cl: green; Br: dark red; I: purple). ..................................................................................................................... 107 Figure 5.1 Top: Possible conversions of nitric acid in aqueous solution; Bottom: Lewis structures of examined nitrogen-containing species. ................................................................................... 114 Figure 5.2 ESP map of DBT showing two regions (labelled as “σ-hole”) of relative positive potential on the covalently bonded sulfur atom. The ESP maps were generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 Two perpendicular perspectives and the corresponding color scale bar are provided for clarity. ...... 114 xxii Figure 5.3 Energy diagram of DBT oxidized by (a) HNO3 and (b) NO2• under standard conditions. ................................................................................................................................... 120 Figure 5.4 The electrostatic potential map of 6a. The ESP map was generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 .......... 129 Figure 5.5 Reaction coordinate diagram of P1 and PC in the 6a reaction system. The total Gibbs energy of all reactants was set as the baseline (0 kcal/ mol). Each plateau represents the total Gibbs energy of all existing compounds (i.e., reactants and products) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ........................................................................ 132 Figure 5.6 Reaction coordinate diagram of the first step in P1 and P2 in the 6a system. The pink area represents an approximation of where the transition state in the P2 pathway lies. The total Gibbs energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs energy of all existing compounds (i.e., reactants, transition state TS, and products) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. .......................................... 133 Figure 5.7 The electrostatic potential map of 6b. The ESP map was generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 .......... 134 Figure 5.8 Reaction coordinate diagram of the first step in P1 and PC reaction modes of 6b with hydrazine. The total Gibbs free energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs free energy of all existing compounds (i.e., reactants and transition state TS) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ............ 137 xxiii Figure 5.9 Reaction coordinate diagram for the conversion of 6b to pivotal 2,1-benzisothiazole compound 34. The total Gibbs energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs energy of all existing compounds at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ........................................................................ 139 xxiv List of Schemes Scheme 1.1 The scheme for the self-exchange SN2 reaction: the reaction process in the presence of XB (on the top); the reaction mechanism in the absence of XB (at the bottom). ..................... 18 Scheme 2.1 Top: C-H cross-biaryl-couplings activated by hypervalent iodine (III) reagent. Bottom: Iodine(III)-induced oxidative dearomatization of phenols to synthesize spirodienones. 26 Scheme 2.2 The hypothetical mechanism of an exemplary hypervalent iodine(III)-induced oxidative coupling. ........................................................................................................................ 27 Scheme 2.3 Synthesis of DPEI-OTf. ............................................................................................ 67 Scheme 2.4 Anion exchange from triflate into chloride for DPEI series. .................................... 68 Scheme 2.5 Anion exchange from triflate into bromide for DPEI series. .................................... 69 Scheme 2.6 Anion exchange from triflate into iodide for DPEI series. ....................................... 70 Scheme 2.7 Anion exchange from chloride into bromide for DPI series. .................................... 72 Scheme 2.8 Anion exchange from chloride into iodide for DPI series. ....................................... 73 Scheme 2.9 Synthesis of DPEBr-OTf. .......................................................................................... 74 Scheme 2.10 Anion exchange from triflate into chloride for DPEBr series. ................................ 75 Scheme 2.11 Synthesis of DPECl-Cl. ........................................................................................... 78 Scheme 2.12 Anion exchange from chloride into triflate for DPECl series. ................................ 79 Scheme 2.13 Anion exchange from triflate into bromide for DPI series. ..................................... 79 Scheme 4.1 Top: Reaction of benzhydryl bromide with various activating reagents in wet CD3CN; Bottom: several examples of tested activators. BArF stands for tetrakis[3,5-bis(trifluoromethyl)phenyl]borate counterion, and pBArF stands for Tetrakis(pentafluorophenyl)borate counterion. ............................................................................ 94 xxv Scheme 4.2 Schemes for the two hypotheses. .............................................................................. 95 Scheme 4.3 Three proposed SN1 reaction pathways, named SN1-null, SN1-a, and SN1-b. ........... 99 Scheme 5.1 The whole process of sulfur conversion of DBT. ................................................... 112 Scheme 5.2 The DFT results showing the oxidative process from DBT to DBTO3 using HNO3 as the oxidant. .................................................................................................................................. 115 Scheme 5.3 The comparison of NO3- and HNO3 as the oxidant (Note: the first oxidative step was chosen as an example). ............................................................................................................... 116 Scheme 5.4 The calculation results showing the oxidative process from DBT to DBTO2 using NO2+ as the oxidant. .................................................................................................................... 117 Scheme 5.5 The calculation results showing the oxidative process from DBT to DBTO3 using NO2• as the oxidant. .................................................................................................................... 118 Scheme 5.6 The calculation result showing the hydrolysis process from DBTO3 to HBPS-. .... 119 Scheme 5.7 Mechanism of desulfonation reaction. .................................................................... 122 Scheme 5.8 The computational result showing the substitution reaction between HBPS’ and OH-...................................................................................................................................................... 122 Scheme 5.9 (a) Structures of 1 (IDC16) and 2 (1C8). (b) Planned synthesis of 3. Numbers in red (structures 6a and 6b) represent the numbering system for the benzisothiazole ring. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ........................................................................ 125 Scheme 5.10 Unexpected reaction course from 6a/6b to 18/19. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ........................................................................................................................ 125 xxvi Scheme 5.11 Competing SNAr and SN2 reaction pathways for the reaction of benzisothiazoles with nucleophiles. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ................................ 126 Scheme 5.12 (a) Reaction of 15 with hydrazine and phenyl- hydrazine. (b) Conversion of 5-nitrobenzisothiazoles 6a and 6b to rearrangement products 18 and 19, respectively. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. ........................................................................ 127 Scheme 5.13 Proposed mechanism for the conversion from 6a to 18. The pivotal Meisenheimer intermediate is highlighted with brackets. .................................................................................. 130 Scheme 5.14 Three proposed pathways in which hydrazine reacts with 6a. The colored arrows represent a thermodynamic change in the first step for each pathway. Red represents an endergonic process, while green signifies an exergonic step. The relative Gibbs energy of each stage (compared to the initial reactants) is indicated in parentheses (units of kilocalories per mole). .......................................................................................................................................... 131 Scheme 5.15 Proposed P1, P2 and PC pathways for reaction of hydrazine with 6b. The colored arrows represent thermodynamic changes in the first step for each pathway. Red represents an endergonic process, while green signifies an exergonic step. The Gibbs energy change is indicated in parentheses (units of kilocalories per mole). ........................................................... 136 Scheme 5.16 Predicted pathway from 3-hydrazino-5-nitrobenzisothiazole 5 to isomeric 2,1-benzisothiazole intermediate 34. To better compare the energy of each compound, two states of hydrazine were used (NH2NH− and NH2NH2). The Gibbs energy change between the reactant and product in each step is indicated in parentheses (units of kilocalories per mole). Red xxvii represents an endergonic process, while green signifies an exergonic step. The formed pivotal Meisenheimer intermediate is highlighted with brackets. .......................................................... 138 xxviii List of Symbols ° degree °C degree Celsius σ sigma π pi σ* sigma antibonding orbital π* pi antibonding orbital → or ← direction of a reaction or charge donation ●●● interactions between two moieties G0 Gibbs free energy under standard conditions ∆ change of a certain parameter Å angstrom δ chemical shift d, t, m (in NMR) doublet, triplet, multiplet in NMR w, m, s (in FT-IR) weak, medium, strong in FT-IR m/z (in HRMS) mass-to-charge ratio in HRMS ?̃? wavenumber ‡ transition state 4e-3c four-electron-three-center xxix List of Abbreviations AcOEt Ethyl Acetate BArF Tetrakis[3,5-bis(trifluoromethyl)phenyl]borate ChB Chalcogen Bonding CPCM Conductor-like Polarization Continuum Solvation Model C-X Carbon-heteroatom DBT Dibenzothiophene DBT-NO2 Nitrobenzothiophene DBT-NO2-int 4-nitro-3,4-dihydrodibenzo[b,d]thiophen-3-ylium and its resonance structures DBTO Dibenzothiophene monoxide DBTO2 Dibenzothiophene dioxide DBTO3 Biphenylsultone DCM Dichloromethane de-M2BrCP Deprotonated 2-bromo-3-carboxy-1-methylpyridinium triflate DFT Density Functional Theory DI Deionized DME Dimethoxyethane DMSO Dimethyl Sulfoxide DPBr Diphenylbromonium DPCl Diphenylchloronium DPEBr Diphenylenebromonium xxx DPECl Diphenylenechloronium DPEI Diphenyleneiodonium DPEX Diphenylenehalonium DPI Diphenyliodonium DPX Diphenylhalonium E Energy EDDM Electron Density Difference Map ESI Electrospray Ionization ESP Electrostatic Potential Et2O Diethyl Ether EtOH Ethanol EXAFS Extended X-ray Absorption Fine Structure FT-IR Fourier-Transform Infrared G09 Gaussian 09 G16 Gaussian 16 HB Hydrogen Bonding HBPS 2-(20-hydroxybiphenyl)sulfonate HRMS High-Resolution Mass Spectrometry LUMO Lowest Unoccupied Molecular Orbital M2BrCP 2-bromo-3-carboxy-1-methylpyridinium triflate m-CPBA Meta-Chloroperoxybenzoic Acid MO Molecular Orbital xxxi M2XP 2-halo-1-methylpyridin-1-ium M4XP 4-halo-1-methylpyridin-1-ium NMR Nuclear Magnetic Resonance OTf Trifluoromethanesulfonate pBArF Tetrakis(pentafluorophenyl)borate PIFA Phenyliodine(III) Bis(trifluoroacetate) QST Quadratic Synchronous Transit SBIs Secondary Bond Interactions SN1 Unimolecular Nucleophilic Substitution SN2 Bimolecular Nucleophilic Substitution SNAr Nucleophilic Aromatic Substitution SSRL Stanford Synchrotron Radiation Laboratory TBA Tetra-n-butylammonium tBuNO2 Tert-Butyl Nitrate TD-DFT Time-Dependent Density-Functional Theory TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl TfOH Trifluoromethanesulfonic Acid TLC Thin-Layer Chromatography TS Transition State UBC The University of British Columbia X Halogen or Halide XANES X-ray Absorption Near-Edge Structure xxxii XAS X-ray Absorption Spectroscopy XB Halogen Bonding XPS X-ray Photoelectron Spectroscopy XRD X-ray Diffraction xxxiii Acknowledgements First of all, I want to express my deepest appreciation to my PhD supervisors, Dr. Pierre Kennepohl and Dr. Suzana Straus. I am so lucky to have Pierre as my principal investigator during my PhD period. He is such an informative and supportive professor whom I can always turn to whenever I need help in research. I am thankful that he has given me the chance to join his research group and expanded my vision to the state-of-art facilities in the synchrotrons. I am also grateful to him for the scientific knowledge, critical thinking, life wisdom he has taught me throughout the PhD studies. I would like to thank Dr. Suzana Straus for her kind help and support during the past five years. She is always so nice, responsible, and encouraging. I would like to thank all the previous and present group members in the Kennepohl group for their kind help. I enjoy the discussions on scientific topics with them during weekly group meetings. Our group members are always willing to offer valuable advice whenever I encounter intractable problems in my projects. I wish to extend my gratitude to my committee member Dr. Chris Orvig, external examiner Dr. Mark Taylor, and examining members Dr. Grenfell Patey and Dr. Mark Thachuk, for participating in the defense process, and providing many insightful suggestions. I especially enjoyed the collaborations with the Grierson group at UBC, the Beer Group at University of Oxford, the Huber group at Ruhr-Universität Bochum, the Love group and Hill group at University of Calgary. Those collaborative projects have broadened my horizons and deepened my understanding in many different areas. xxxiv Special thanks to the faculty and staff at the University of British Columbia and University of Calgary (during my visiting period). They have taken time to offer help and inspired me in the research progress. I would like to offer my enduring gratitude to the beamline scientists Dr. Matthew J. Latimer, Dr. Erik Nelson, Dr. Leah Kelly at Stanford Synchrotron Radiation Lightsource (SSRL) and Dr. Mohsen Shakouri, Dr. Roman Chernikov, Dr. Emilio Heredia at Canadian Lightsource for their friendly support and patience during those synchrotron trips. I am so glad that I have made so many friends from all over the world during my PhD journey. They have shown me the magic of friendship and cultural diversity. Their company has brightened my after-school life. Last but not least, I am extremely grateful to my beloved family members. They are always there for me whenever I feel frustrated or discouraged. They have given me the strongest and the warmest support throughout my life. xxxv Dedication This thesis is dedicated to my beloved parents and grandparents: • Thank you, my dad, for teaching me how to be brave and firm when I encounter difficulties in life • Thank you, my mom, for inspiring me with endless love and support • Thank you, my grandparents, for the warmest care 1 Chapter 1: Introduction Weak interactions such as hydrogen,1 halogen,2 chalcogen,3 pnictogen,4 and tetrel5 bonds have shown their tremendous importance in chemistry and biology in the past decade. Those interactions are most commonly used as the junctions in supramolecular motifs.6 The success of such weak and reversible bonds in the design of supramolecular assemblies has also spurred expansion into other fields, like biosensors,7 efficient extraction technologies,8 and surface modifications.9 Among those interactions, hydrogen bonding (HB) has drawn the most attention as it combines the general simplicity with relatively high binding strength (sometimes up to 40 kcal/mol).10 However, other alternatives deserve more attention if structurally diverse and multifunctional systems are desired. 1.1 Halogen Bonding Halogen bonding (XB) is a class of weak interactions that have been known for over 50 years. XBs are highly directional, short-range interactions between a covalently bonded halogen and a Lewis base.11 Long considered as interactions that were adventitiously observed in the packing of halogen-containing crystalline solids, its observation in biological systems2,12 and subsequent application in crystal engineering13,14 and supramolecular chemistry,15 led to a dramatic increase in interest over the last decade. More recently, the use of XB interactions has exploded in a wide range of other fields including molecular recognition,16–18 solar energy conversion,19,20 and catalysis.21,22 The nature of halogen bonding and its influence on the properties of complex systems has become extremely relevant. There has existed for many years a simmering debate regarding the nature of halogen bonds.23 The predominant approach to describing halogen bonds has been the σ hole model, which focuses 2 on the pre-eminence of classical electrostatics as the driving force for XB interactions.24 The covalently bound halogen atoms exhibit an electron-deficient region that results from localization of electron density to form the σ bond (Figure 1.1). The resulting “σ hole” is therefore an electron-deficient region that can interact with electron-rich species. It has been shown that the strength of many XB interactions correlates very well with the magnitude and size of the σ hole as one would expect for an electrostatically driven process.25–28 In such model, electrons are localized on each interacting species. Concurrently, the possibility of charge transfer (or covalent) contributions to such chemical bonds has been invoked for decades.29,30 Most notably, charge transfer contributions have most often been invoked to explain spectroscopic and electron transfer properties of XBs.29,31–34 At first, these two points of view centered on which of these bonding contributions was most important in defining the strength of XB interactions. In fact, this debate has hampered a more reasonable - and relevant - discussion of this interaction: the properties of XB should not be confined to evaluating bond strengths and/or bond lengths. Bond strengths might be important in determining specifics about adiabatic energy profiles for ground-state chemical reactions and related parameters. However, the plethora of applications for which halogen bond and related interactions have been used clearly indicates that there are other variables that are important beyond binding constants and bond strengths. Other characteristics, like catalytic and selective properties, are typically very sensitive to specifics of the chemical interactions and not to their overall strength directly.16 Those properties deserve more attention in our ways of discussing halogen bonds. 3 Figure 1.1 A cartoon showing the debates between “electrostatic team” and “covalency team”. The XB pair (CH3Br and Cl-) is taken as an example here. The molecular orbital diagram above “covalency team” shows the main idea of the covalency-based theory, where electrons are donated from the nonbonding orbital of Cl- (nCl) to the antibonding orbital of the C−Br bond (σ*C−Br). The scheme above “electrostatic team” depicts the σ hole on the extension of C−Br bond, which interacts with the negatively charged Cl-.§ One goal of this thesis is to first emphasize a more comprehensive portrayal of XB, taking into consideration of electrostatics, charge transfer and other related quantum chemical effects. In different systems, the ratio of each component varies and could make a significant difference on XB properties. Furthermore, XB characteristics are not limited to energetic and structural descriptors. Different properties of XB should be highlighted in different application systems. The perspective provided by this holistic model of XB will enable more rational designs of applications involving XB. § Molecular orbital (MO) diagram and electrostatic potentials were generated using Gaussian0935 with the B3LYP theory/Basic(3-21G) basis set36 and visualised using WebMO.37 In MO diagram, The MO isosurface value is set to 0.050. The yellow/green represents antibonding orbitals while the blue/red stands for bonding or non-bonding orbitals. In the electrostatic potential map, the density isosurface value is 0.003. Bright blue and bright red represent -0.035V and +0.035V, respectively. 4 As it is mainly related to the electron distribution throughout the bonds, the terms donor and acceptor in the work will be used to represent the electron donor (i.e., Lewis base which can provide electrons) and electron acceptor (i.e., covalently bonded halogen, hydrogen, or chalcogen), though this is the reverse of the typical terminology for XB. 1.1.1 “Dominant Role”: Electrostatics? A significant advance in understanding XB came through the surge of halogen-involved crystal engineering.38,39 There are two main kinds of frameworks discovered in crystal structures (see Figure 1.2 top): (1) Type 1 -- In the most typical XB genre, covalently bonded halogen in molecules RX closely contacts with the nucleophile along the extended R−X axis (with an angle of 170° − 180°); (2) Type 2 -- Interactions with electrophiles occurs mostly at angles between 90° and 120° with the R−X bond.25 Based on these two types of structures, it is appropriate to conclude that the electron density is distributed unevenly on the surface of the covalently bonded halogen. More precisely, it is electron deficient at the extension of R−X bond, while electron rich in the central part of the halogen atom. This hypothesis was perfectly matched with the subsequently developed electrostatic potential simulations.40 The concept of “σ hole” was established hereafter. The covalently bonded halogens (Cl/Br/I) closely approximate the s2px2py2pz1 configuration (see Figure 1.2 bottom), in which the z-axis aligns with the R−X bond.24 It depicts a positive region at the extension of R−X bond surrounded with a donut-shape ring of negative potential, which is named the “σ-hole” as shown in Figure 1.1. 5 Figure 1.2 Two kinds of frameworks in the halogen-involved crystals (top); s2px2py2pz1 configuration in which the s orbital is omitted (bottom). The electrostatic potential (ESP) has been widely used to analyze weak interactions, in which the V(r) are calculated on the molecular surface using 0.001 electrons Bohr-3 contour of ρ(r).41 Scientists found that the donating and accepting tendencies can be quantitatively predicted from VS,max and VS,min (i.e., the most positive and negative values of the surface electrostatic potential), respectively.42,43 Therefore, the degree of electrostatic interaction in XB is usually characterized using ESP. σ-hole theory in conjunction with electrostatic potential analysis has been successfully applied in the fields of crystal structure prediction,44 drug discovery, and modelling45 as it is simple, intuitive, and practical. One of the major claims in the σ-hole theory is that the strength of “σ-hole” type interaction is linearly correlated to the magnitude of the σ-hole (i.e., the most positive electrostatic potential VS,max on the electron acceptor). In other words, Lewis acid R−X with a more electron-withdrawing R group tends to form stronger XB with a certain Lewis 6 base.46,47 This argument has been evidenced in many XB-involved systems,47–49 and thus is usually taken as a strong proof of the dominant role of electrostatics when defining XB. Other components also exist but often in small amounts, like polarization, dispersion, exchange, Pauli repulsion, charge transfer, orbital interaction, electronic correlation, delocalization, deformation, etc.27,50 Some proponents of the σ-hole model have denied the concept of charge transfer, taking it as a deformation of polarization; since it is difficult to separate the two characters using computational methods.27,51. Given that electrostatics is much more measurable (using ESP) than charge transfer, and usually makes up most of the binding energy, the electrostatic component is naturally considered as the primary or even the only factor in many discussions of XB. 1.1.2 The More, the Better? The σ-hole concept has provided an intuitive visualization of the electron distribution on the interacting halogens, meanwhile the derived “electrostatically driven model” has adequately rationalized a majority of XB systems. The σ-hole theory was for a long time considered as the “touchstone” of XB and other similar weak interactions. It emphasizes the dominant role of electrostatics due to its major contribution to the binding energy of XB in most cases. However, the theory is untenable if other quantum chemical effects like charge transfer and the Pauli repulsion are not taken into consideration. 1.1.2.1 “Counter-Intuitive” Computational Models Case 1 In the case of F−Cl∙∙∙SiN−R, where R equals to F, Cl, C≡CH and C≡CF, the initial surface potentials of both binding sites are positive.52 When each motif is examined individually, the chlorine in F−Cl possesses a positive σ-hole (around 40 kcal/mol as shown in Figure 1.3) and the silicon in each SiN−R is also positive (in the range of 3.4 − 7.0 kcal/mol on its outermost surface). However, the formation energies of XB in the F−Cl∙∙∙SiN−R complexes are in the range of -4.2 − 7 -1.9 kcal/mol, indicating a favorable binding interaction between two partially positive areas. In the “electrostatics-driven model”, the polarization of the silicon by the electric field of the chlorine on F−Cl induces negative potentials on the extension of N−Si bond, thus turning the initial electrostatic repulsion into an attraction interaction.53 However, the explanation does not stand up to scrutiny. Dipole-dipole interaction would separate the two positive regions on each molecule right after F−Cl encounters SiN−R. In other words, the chlorine in F−Cl would prefer to approach the portion with negative potential in SiN−R. The likelihood of the above-mentioned polarization may therefore be very low if the “presumably” interacting motifs cannot “see” each other. However, more computational studies on it are required to address this hypothesis. Figure 1.3 Computed electrostatic potential on the 0.001 au molecular surface of F–Cl. The chlorine is in the foreground. Color ranges, in kcal/mol, are as follows: red greater than 20; yellow from 10 to 20; green from 0 to 10; blue less than 0 (negative). The position of the VS,max on the chlorine is denoted by a black hemisphere; its value is 39.9 kcal/mol. Reprinted by permission from [Springer Nature Customer Service Centre GmbH]: [Springer Nature] [Theoretical Chemistry Accounts] [Politzer, P., Murray, J.S. Halogen bonding and beyond: factors influencing the nature of CN–R and SiN–R complexes with F–Cl and Cl2 . Theor Chem Acc 131, 1114 (2012). https://doi.org/10.1007/s00214-012-1114-1, [Copyright © 2012] Case 2 A particularly notable example is the complexation of CX3I (where X = F, Cl, Br, and I) and several common electron donors, where the σ-hole trend is exactly opposite to the trend of 8 XB strengths.54 The magnitude of the σ-hole decreases from CF3I (28.5 kcal mol-1) to CI4 (25.5 kcal mol-1) as expected. The actual interaction strengths of CX3I with chloride (or trimethylamine), however, increases from CF3I to CI4 (ΔEint = -29.3 kcal mol-1 for CF3I∙∙∙Cl- and ΔEint = -37.0 kcal mol-1 for CI4∙∙∙Cl-). This example challenges the general applicability of the electrostatic theory since the magnitude of σ-hole does not correlate to the binding strength in this case. Energy decomposition analysis and natural population analysis (it derives from natural bond orbitals and leads to the determination of natural atomic orbitals.55) further revealed that both the electrostatic and charge transfer proportion in the overall energy increase from X = F to X = I, while the charge-transfer contribution changes by a larger degree than the electrostatic contribution as the overall energy changes.54 This reflects an increased role of the charge-transfer component, as opposed to that of electrostatics, in this case. In such covalency-dominant scenarios, the overlap of relevant orbitals makes a significant difference in the nature of XB. In other words, the better match of the σ* orbitals of R-X bond and the corresponding electron donor orbitals is a key factor of stabilizing the XB interaction, rather than merely increasing the electronegativity of R groups. Case 3 The Head-Gordon group has shown the different effects of charge transfer and polarization on XB and that the description of XB is improper without charge transfer.50 CX3I∙∙∙F- (X = F, I and NO2) were examined using the energy decomposition analysis combined with a potential energy scan. As the XB bond length of CX3I∙∙∙F- (X = F, I, and NO2, respectively) increases, the frozen interaction, polarization, dispersion, and charge transfer components act separately, thus producing a dynamic total energy curve. The importance of each component varies in the three examined XB pairs: (1) Electrostatic component dominates in CF3I∙∙∙F- but charge transfer favors CI4∙∙∙F- strongly enough to surpass the electrostatic influence. (2) The binding energy of C(NO2)3I and F- is up to 260 kJ mol-1, falling in the range of some covalent bond 9 energies, since the nitro group combines the high electronegativity and impressive charge-transfer ability. This demonstrates a special case in which the charge transfer and electrostatics are both essential and synergistic in effect. (3) Unexpectedly, the polarization energy of C(NO2)3I lies between that of CF3I and CI4, which does not follow the trend of the energy generated by the charge-transfer component (Note: the absolute value of energy generated by charge transfer follows this trend: C(NO2)3I > CI4 > CF3I). This demonstrates the different nature of polarization and charge transfer. Overall, a portrayal of XB that mixes up charge transfer and polarization or simply ignores both components would be inappropriate. Upon further reflection (see Figure 1.4 top), the nitro group could be co-planar with C-I bond so that the π electrons in C(NO2)3I would delocalize throughout the whole molecule, and the C(NO2)3I may form both σ and π interactions with F-. CF3I and CI4, in contrast, could only form σ interactions with F- due to their tetrahedral geometry (The schemes of simplified σ- and π-type interactions are shown in Figure 1.4 bottom). This explains why the C(NO2)3I has the highest binding strength with F- to some extent, which also corresponds to the commonly known concept “resonance effect” in organic chemistry.50 10 Figure 1.4 Proposed modes in CF3I ∙∙∙ F- and C(NO2)3I ∙∙∙ F- adducts, in which the purple atoms are iodine atoms, the green atoms are fluorine atoms, the blue atoms are nitrogen atoms, the grey ones are carbon atoms, the red ones are oxygen atoms, the dash line represents the XB interaction (top). Schemes for σ- and π-type interactions (bottom). 1.1.2.2 Experimental and Spectroscopic Findings The importance of charge transfer was not only verified by computational models, but also reinforced by some experimental and spectroscopic findings as follows. Case A I3- could be considered as a limiting case of halogen bonding. The mixture of electron donor I- and electron acceptor I2 can lead to the formation of I3- in an exergonic equilibrium. The reaction process can be regarded as a dynamic transition from a secondary bond to a primary bond and vice versa (see Figure 1.5a). I- was initially attracted to the I2 molecule in a linear orientation. A lone pair on I- was then donated into the σ* orbital of the I2, thus weakening the I−I bond in the I2 molecule and ending up with a delocalized four-electron-three-center (4e-3c) structure.56 The whole process is supposed to be a dynamic transition from X ← D halogen bond to X-D covalent 11 bond. By the same token, Br3- and Cl3- species also exist, but with lower stability. The increasing polarizability of halogens along the group leads to better energy matching of both σX-X and σ*X-X orbitals with Xp orbital on X- (X = Cl, Br or I) as illustrated in Figure 1.5 (b).57 In a similar manner, the evolution from outer complexes (i.e., H3N···ClF and (CH3)3N···ClF) into inner complexes (i.e., [H3N−Cl]+···F− and [(CH3)3N−Cl]+···F−) were evidenced by rotational spectroscopy.58,59 This type of equilibrium vividly demonstrates a covalency-dominant XB mode, making it possible for XB pairs to communicate by electrons. It also implies the possible transition of halogen bond to primary bond, and vice versa.60 Similarly, the crossover from hydrogen to primary bonding has also been evidenced by femtosecond two-dimensional infrared spectroscopy lately.61 This model can also be used to explain the abnormal phenomenon in the aforementioned Case 1 (F−Cl···SiN−R model). The covalent component in XB has played a crucial role here. The lone pair on the extension of N−Si bond donates electrons into the σ* orbital of F−Cl bond via XB, thus forms a 4e-3c delocalized system. Due to the similar atomic sizes and orbital energies of Cl and Si, the significant overlap between the non-bonding orbital on Si side and the σ*F−Cl orbital on the other promotes the formation of XB in a more effective manner. A recently reported XB-assisted self-association of anionic pairs has also highlighted the effect of covalent contributions in XB, where a series of iodinated bis(dicyanomethylene)cyclopropanid derivates can be stabilized by halides.62 12 Figure 1.5 (a) A dynamic perspective of I3-; (b) A molecular diagram showing the formation of I3-. Case B X-ray absorption spectroscopy (XAS) was initially developed as a useful tool for quantitatively evaluating covalency in metal−ligand bonds in the 1990s by Solomon group, and was later applied in more generalized donor-acceptor systems (For more information on XAS techniques, please refer to section 2.3.2.1).16,63,64 XAS was employed to experimentally examine the explicit content of charge transfer in solid-state I2X- and I4X- materials (in which X = Cl, Br).34 This system is very similar to those in Case A (I2···I- model) where X- is a strong Lewis base interacting with a Lewis acid I2 (or I4). As expected, the charge-transfer component is extremely large in solid-state I2X- and I4X- (The total charge donation was found to be around 25% from both DFT calculations and XAS data) and that one halide donor can simultaneously interact with multiple electron acceptors though charge transfer.34 Case C In a conventional XB construction, R-X∙∙∙D, a neutral halogen X is covalently attached to a substituent R and meanwhile interacts with a neutral electron donor D. In Case A and B (I2∙∙∙X- 13 model), strong XBs were induced by a negatively charged electron donor with higher nucleophilicity. Likewise, if a R-X motif carries a positive charge, the XB strength is expected to be stronger than neutral ones. Halonium system is thereof an important subset. Halonium ion, a positively charged halogen X+, forms XBs with two Lewis bases simultaneously, often expressed as [D∙∙∙X+∙∙∙D]. Depending on the properties of electron donors and halonium ion, the nature of formed [D∙∙∙X+∙∙∙D] complex varies: Among the four primary halogens [iodine (I), bromine (Br), chlorine (Cl), and fluorine (F)], fluorine generally forms a structure of [N−F+∙∙∙N], with a distinct short N-F covalent bond and a longer F+∙∙∙N halogen bond. The other three halogens are commonly observed in the 4e-3c delocalized [N∙∙∙X∙∙∙N]+ fashion, which were evidenced in nuclear magnetic resonance (NMR) spectra.65,66 The natural bond orbital analysis reveals that the stabilization of XB is mainly contributed to the charge delocalization from the lone pair on one of the nitrogen atoms into the σ*N-X orbital on the other.66 The partial covalent character in the three-center XB decreases as the size of halogen atom increases. However, the XB bond strength follows the opposite trend. More specifically, the bonds in [N∙∙∙Cl∙∙∙N]+ were observed to be the weakest despite of its largest covalent contribution, while the least covalent [N∙∙∙I∙∙∙N]+ system exhibits the strongest XB.66,67 When X changes from Cl to I in [N∙∙∙X∙∙∙N]+ system, the size and energy of σ*N-X orbital would vary, thus altering the overlap degree between σ*N-X orbital and non-bonding orbital on the other nitrogen. Considering the relatively similar atomic size of Cl and N, the XB in [N∙∙∙Cl∙∙∙N]+ is expected to possess more covalent character. Nevertheless, the energy benefit from covalency may be inadequate to compensate the polarization effect so that the [N∙∙∙I∙∙∙N]+ has the strongest XB. 14 1.1.3 Different Scenarios, Different Focuses The counter-intuitive instances discussed above raise questions about when the simple and commonly accepted electrostatic descriptions of XB fail and more consideration of the electronic structure becomes important. For this reason, there are differing viewpoints on how to best describe the interactions in halogen bonds and what contributes more or less to their bond strengths. However, these debates ultimately miss one important point: bond strength is not the only aspect of the properties of a chemical bond. Other relevant properties (such as electrochemical properties, catalytic performance, and selectivity) are often more decisive than binding energies in many specific cases. Crystal engineering (directionality) Crystal engineering is a field of designing and building functional solid-state structures from neutral or charged building blocks, mainly connected by intermolecular and intramolecular interactions. In often cases, the binding site, bond angle and overall architecture are the main focuses. Directional and strong enough molecular interactions are generally introduced to establish a desired structure. Given that the σ-hole and the lobe of the σ* orbital of the R-X bond are in the same place, a decent prediction of XB-involved crystal structure can usually be achieved based on either covalent or electrostatic component or both terms. Considering the more intuitive electrostatic potential map, electrostatic contribution is often chosen as the basis of determination.68–70 Anion recognition/self-assembly (selectivity) Compared with crystal engineering, anion recognition requires higher selectivity, namely stronger interactions. Complementary size and shape of the binding partners, favourable binding geometries and energy stabilization are necessary in a successful anion assembly. In most instances, self-assembly (or anion recognition) relies on the Coulombic attraction of counterions to improve binding affinities. Therefore, electrostatic 15 characteristic is normally regarded as the main factor.17,71 Notably, Beer and co-workers have experimentally and computationally revealed that acyclic XB receptor possesses better selectivity in anion recognition over the HB analogue due to the relatively higher covalent contributions.16 Shaik group has also theoretically confirmed that charge transfer in XB is a key player in its greater selectivity and improved geometric constraints than HB.72 The extent of charge transfer thus should not be neglected in such XB-based anion recognition systems. Electrochemical applications (electrochemical properties) XB-involved electrochemical devices, like dye-sensitized solar cells,19 hybrid perovskite solar cells,20 and electrochemical sensor,73 have triggered tremendous interests in the past decade. Those applications generally involve different electron-transfer reactions at various stages. It can therefore be assumed that the efficiency of electrochemical devices is correlated to the extent of the interactions among relevant molecules, especially of the charge-transfer components. An analysis of spectroscopic data that testifies the clear existence of covalency in XB was reported recently.74 The dye-sensitized solar cell was fabricated by the Dye−X molecules consisting of a redox-active triphenylamine core and halogenated substituents (X = Br or I) which is mounted on a metal oxide surface. Though the Dye−X compound itself is a poor electron acceptor in the neutral form, the transformation of it by one-electron oxidation to its radical cation state Dye−X•+ makes the triphenylamine core much more electron-withdrawing and thus generates a strong XB.19 To obtain mechanistic information of how XB is potentially affecting electron-transfer rates, the covalent compositions within Dye−X•+∙∙∙Cl– were well resolved using the XAS technique mentioned in Case B. Time-dependent DFT simulations of XAS data have illustrated the formation of a half-occupied π orbital of Dye-X•+ with markable π-orbital donations from Cl– (π* ← Cl1s) and σ*-type orbitals generated by σ* orbitals on Dye-X•+ and the 3p orbitals of Cl– (σ* ← Cl1s), respectively.74 It has highlighted the 16 decisive effect of charge transfer in determining electrochemical properties of XB. Except for σ-interaction, π-covalency in XB should also be addressed whenever the XB pairs have matched π-symmetric orbitals that are close in energy. Figure 1.6 The structure of Dye-X•+(left). The two graphs on the right are reproduced from reference [72] without further changes (© Creative Commons). The experimental XAS spectra (black lines) of Dye-I•+···Cl– (a) and Dye-Br•+···Cl– (b) and the corresponding TD-DFT simulated spectra (calculated using BP86, solid orange lines) are shown along with the relative oscillator strengths of the individual calculated transitions (vertical gray lines). The height of the simulated edge peaks was normalized to the height of the experimental edge peak. The transitions corresponding to pre-edge features were visualized as electron density difference maps (EDDMs) at an isovalue of 0.0004 (inset). The blue lobes represent positive changes in electron density corresponding to the acceptor orbital(s) of the transitions, while the donor orbital was always the chloride 1s (indicated by a negative change in electron density in red and not always visible). In order to highlight the pre-edge features resulting from σ- and π-covalency in Dye−I•+···Cl– and Dye−Br•+···Cl–, truncated versions of the simulated spectra excluding the high energy Cl4p ← Cl1s edge peak transitions were also generated (dotted orange lines). Catalytic activation (catalytic properties) The application of XB in catalysis has been extensively explored in two ways: using halogenated Lewis acid activators to influence the reactivity of partner Lewis bases; optimizing Lewis base catalyst to modulate the activity of the NSX XOOHNClDye-X•+···Cl–17 Lewis acid (see Figure 1.7).75 No matter which strategy is adapted, such catalytic reaction involves three steps: (1) the electron donor first binds to the leaving group X via XB interaction; (2) then the R−X bond is elongated; (3) the R−X bond is dissociated eventually. It has been demonstrated that the elongation of the R−X bond via XB is the outcome of the charge transfer to the R−X σ* orbital by using natural bond orbital analysis and block-localized wave function method.76,77 Therefore, the charge-transfer component is essential in the course of XB-induced catalysis. In the previous examples, the XB was formed on the extension of R−X bond where it directly participated in the elongation of covalent bonds. Interestingly, the Kennepohl group has designed a novel system where Lewis base catalysts regulate reactivity via a spectator XB in a self-exchange SN2 reaction (see Scheme 1.1) (This computational work was carried out with M06-2X functional, aug-cc-pVDZ-PP basis set for iodine, jun-cc-pVDZ for all other elements in the gas phase at 298.15 K, and 1 atm).75 During the SN2 reaction (CR2I2 + I- → I- + CR2I2), the reactants go through a trigonal-bipyramidal-shaped transition state before proceeding to the desired products. If a Lewis base participates in the formation of the transition state during which it binds to the equatorial iodine atom through XB, the reaction barrier would change accordingly. It turns out that only PF3 shows activation effect among three testing donors (i.e., NH3, CO, PF3). The charge redistribution modulated by XB is considered to have a significant impact on the stability of transition states. As shown in Figure 1.8, the strong σ-donor character of NH3 destabilizes the transition state by increasing electron density along the primary I−C−I axis (i.e., the vertical axis) and thereby elongating both C−I bonds. In contrast, PF3 as a weak σ-donor and strong π-acceptor would stabilize the transition state by decreasing the electron density in the vertical C−I bonds through π-backdonation from two terminal iodides, and simultaneously increasing that in the horizontal “C−I∙∙∙PF3” moiety. The poor orbital overlap of CO with the large valence I5p orbitals might be 18 responsible for the ineffectiveness of CO, even if it is often viewed as a strong π-acceptor. This systematic study upon a model SN2 reaction does not merely demonstrate the potential impact of specific orbital interactions on chemical reactivity via XB, but further attested the significance of charge transfer - even in π-type manner - within the context of catalytic activation. Considering the widespread use of molecular orbital (MO) theory as an effect tool of interpreting chemical phenomena, using covalency as a XB descriptor with the assistance of MO analysis should be appropriate and efficient in the field of chemical catalysis.75 Figure 1.7 Two common modes of activation in XB-assisted catalysis. On the left, the Lewis acid (R−X) is usually the catalyst, while the opposite strategy on the right uses a catalytic Lewis base. The green shaded part is the activator that modulates the reactivity of its partner. Scheme 1.1 The scheme for the self-exchange SN2 reaction: the reaction process in the presence of XB (on the top); the reaction mechanism in the absence of XB (at the bottom). 19 Figure 1.8 Schematic representation of the catalytic SN2 reaction and electron-density flow in each of the transition state structure. This figure has been adapted from reference [75] with the permission from the authors (© Creative Commons). The nature of XB depends on the properties of interacting partners and the environmental influences like electric field, solvent, and temperature changes. A purely electrostatics-driven model is insufficient to describe XB systems, especially for the stronger ones. Polarization, dispersion, and charge transfer should all be included in the discussion of XB. In particular, charge transfer makes a considerable difference in a σ-donation manner, or even together with π interactions. Furthermore, most studies on XB focus on its binding strength, or bond energy (the measure of bond strength). However, there are many difficulties using binding strength as a decisive factor in the discussion of XB. In the first place, bond energy is defined as “the average value of the gas-phase bond dissociation energies (usually at a temperature of 298 K) for all bonds of the same type within the same chemical species” in IUPAC.78 Radicals will be formed after the bond dissociation as the electrons are equally split. It’s worth noting that the dissociation of weak interaction is heterolytic cleavage, thus the measurement of binding strength of weak interactions is burdensome though we can use mass spectroscopy to assist. Secondly, the bond energy is only related to the enthalpy obtained from gas phase, while the widely applied XB systems are often in solid or 20 solution state. Using the bond energy to predict the XB behaviors in solution or solid state is improper, since the significant entropy effects are expected to have big impact on the properties of XB. In addition, comparison between the computational and experimental results of energy is difficult. The current solvation model in DFT calculation cannot well simulate the solvation effects, especially for the entropy part. We may solve this problem by either using molecular dynamic method or explicitly adding many solvent molecules around the investigated molecules, but it requires higher computational cost. Therefore, our scope of XB should never be constrained by binding energy or geometric features. Other interesting characteristics of this interaction are worth noting, such as electrochemical, catalytic, and selective properties. When it comes to different properties in various scenarios, the focus of our attention should change accordingly. This thesis is expected to have potential implications for the design of XB-applied systems. 1.2 Chalcogen Bonding Chalcogen bonding (ChB), defined as the interaction between a covalently bonded chalcogen atom (e.g., O, S, Se, Te) and a Lewis base, is also an important type of weak interaction like XB.79 Compared with XB, ChB has received much less attention, though it occurs in many chemical and biological processes.3 In this section, an introductory review of ChB is provided, especially in comparison with its “sibling” -- XB. 1.2.1 Comparison of Chalcogen Bonding and Halogen Bonding 1.2.1.1 Similarity ChBs and XBs have often been applied in similar fields, but ChBs have been less invoked compared to XBs. Like most weak interactions, ChB was first clearly resolved and applied in crystal engineering. Cyclic, linear, tubular assemblies have been established in those ChB-involved crystals.80–82 21 If the strength of ChBs is enhanced by using either cationic or polyfluorinated backbones, ChBs are expected to expand the range of their applications. For instance, if the ChB strength is strong enough to overcome the interference from the solvents, the selectivity of ChB complexes would stand out. This is the mechanism behind its more recent implications in anion recognition,83 anion transport,84 and organocatalysis.85 1.2.1.2 Differences Binding mode ChB system is usually more complicated than its XB analogy due to the presence of two electrophilic areas on the covalently bonded chalcogen atom. As illustrated in Figure 1.9, the divalent chalcogen can form one ChB with the incoming electron donor at the extension of R1−Ch bond. Under certain circumstances, the chalcogen atom can also be involved in two ChBs simultaneously. The two binding modes have increased the structural diversity of ChB-based systems. Figure 1.9 Two common modes in ChB-based systems. Spin properties Given its weaker binding strength relative to XB, ChB has often been neglected in many chemical systems. However, the applicability of XBs in molecular electronics may be restricted by the inherent weakness and photochemical susceptibility of C−X bonds. Furthermore, the inherent spin of halogen nuclei can also be problematic in situations where scalar coupling is ChR1R2D1 ChR1R2D1D2ChB mode 1 ChB mode 222 a limiting factor. In principle, both of these limitations can be overcome by shifting from XBs to ChBs for molecular assembly. The greater stability of the building blocks, as well as the integer nuclear spin of the chalcogen nuclei offers distinct advantages. Covalent or non-covalent? As discussed in section 1.1, the nature of XBs is still under debate. It has been experimentally resolved that the charge-transfer component is a significant factor in many XB cases.16,19,34,74 Unlike XBs, ChBs are commonly known as non-covalent weak interactions which are purely driven by electrostatics. Till now, scarce references have pointed out that charge transfer plays an important role in ChBs to a substantial extent.86,87 In addition, the covalent contribution was only computationally evaluated in those references. Direct probe of such component using experimental methods has not been reported so far. In Chapter 3 of this thesis, the first spectroscopic evidence for covalency in ChBs will be presented. 1.3 Thesis Aim The aim of this thesis is as follows： (1) To probe the nature of XB in ionic model systems XBs are often entangled in complicated chemical or biological assemblies, which makes it difficult to investigate the nature of XB itself. In chapter 2, several simple but representative ionic salts (hypervalent halogen salts) were selected as the model systems to investigate XB interactions. NMR, XRD, XAS and other useful techniques have been applied to provide a thorough understanding of XB. (2) To elucidate the nature of ChB in ionic model systems Compared with XB, the study on the electronic properties of ChB systems is lagging behind. To our best knowledge, there are only few papers that have deeply investigated the electronic structures of ChB interactions using computational methods.86,87 In chapter 3, the first experimental evidence 23 of covalent contributions in ChB systems using XAS techniques will be shown. A series of bis-triazole-pyridinium-containing salts were chosen as the ChB model systems, meanwhile the HB and XB analogs were provided for comparison. (3) To explore the function of XB in halogen-involved chemical reactions The effort that has been made to understand the fundamentals of XB allows for a more rational design of XB-based applications. In chapter 4, a carbon-halogen bond cleavage process was examined with and without the participation of halogen-containing activators. A benchmark substitution reaction of benzhydryl bromide was studied. Two types of organic salts were selected as the activators, with polyfluorinated and imidazolium backbones, respectively. DFT calculations were employed to investigate the mechanistic pathways of the reaction; XAS techniques, along with the TD-DFT analysis, have implied the importance of covalent contributions in XB throughout the organocatalytic process. (4) From XB to ChB: to demonstrate the significance of ChB in chalcogen-containing chemical reactions Chalcogen chemistry, especially sulfur chemistry, is an important branch of the main-group chemistry. Organic chemists usually focus on the electron flow from one substance to another but sometimes ignore the pre-equilibrium stage before the initiation of a reaction. Weak interactions are readily established during the pre-equilibrium period, after which the reacting molecules orientate in a more desired way. In chapter 5, two practical systems were explored to find out the role of ChB in sulfur-containing reactions. The first section has uncovered the importance of ChB in the sulfur oxidation reaction within the petcoke (i.e., petroleum coke) modification process. The manuscript based on this work is under review. The second part has revealed the mechanistic pathways 24 of benzisothiazole conversions and the effect of sulfur groups thereof. Part of this work has been published (DOI: https://doi.org/10.1021/acs.joc.1c00118). 25 Chapter 2: Probing the Nature of Halogen Bonding in Ionic Systems To study the nature of XB, a proper model system is required. It should involve stable XBs that are not readily overwhelmed by other interactions. In literature, much effort has been dedicated to enhancing the strength of XB. One of the approaches is to increase the electrophilicity of the neutral Lewis acid by introducing more electron-withdrawing substituents (e.g., polyfluorinated or aromatic moieties) into the backbone.88 Alternatively, XBs can be strengthened by using charged partners to form “charge-assisted” adducts.89 A competitive study employed by Huber group has shown that cationic XB activators have much better performances than their neutral polyfluorinated counterparts in a bench mark reaction.90 Therefore, we synthesized a series of ionic model compounds to probe the nature of XB between ionic pairs in this chapter. When it comes to the chemicals with cationic core structures, pyridinium-derived molecules are usually referred to. Two different types of pyridinium model systems have been investigated herein (see Appendix A and B). However, the synthesized complexes are unstable in the presence of halides or water due to the rapid nucleophilic aromatic substitution (SNAr) reactions induced by the strong electron-withdrawing effect of the cationic pyridinium core. Hence, a more stable compound series is required to study the properties of XB free of side-reaction interferences. Hypervalent halogen (III) compounds have spurred intensive attention in organic synthesis, especially for the hypervalent iodine (III) complexes.91 Iodine (III) reagents have been extensively used in metal-free oxidative coupling processes to achieve C-H functionalization92 and phenol oxidation93 as illustrated in Scheme 2.1. The developed methodologies have also been applied in some pharmaceutical and agrochemical processes as they are safe, sustainable, and relatively stable.91 For instance, the first hypervalent-iodine-induced cross-coupling reaction of aromatic 26 compounds was discovered by Dohi et al. in 2008.94 The coupling of naphthalenes and alkylbenzenes was achieved in a high yield with the assistance of phenyliodine(III) bis(trifluoroacetate) (PIFA) and the activator of PIFA (i.e., boron trifluoride diethyl etherate). In the proposed mechanism (see Scheme 2.2), the electron-deficient iodine in PIFA activates naphthalene via a single-electron transfer process, which is prompted by the cation-π interaction between iodine and the aromatic system. The charge-transfer complex formed in the first step indicates the relatively strong electrophilicity of iodine (III) and its potential as a charge-transfer acceptor. The addition of boron trifluoride diethyl etherate further depletes the electron density on PIFA, hence improves the electrophilicity of iodine (III) and triggers the single-electron transfer process. In fact, such cation-π interaction is a special form of XB. It is originally invoked by the affinity between the electron-deficient regions on halogen and a Lewis base. If such interaction is strong enough, charge-transfer complex can thus be generated. Scheme 2.1 Top: C-H cross-biaryl-couplings activated by hypervalent iodine (III) reagent. Bottom: Iodine(III)-induced oxidative dearomatization of phenols to synthesize spirodienones. 27 Scheme 2.2 The hypothetical mechanism of an exemplary hypervalent iodine(III)-induced oxidative coupling. Despite the extensive exploitation of hypervalent iodine (III) in organic reactions, the systematic study on its electronic and geometric properties is still lagging behind. In recent years, Huber and Bolotin groups have explored the application of iodine (III) as the Lewis acid in Ritter-type solvolysis and Knorr-type reactions.95,96 The XB strength of those iodine (III) compounds have been confirmed to be higher than strong iodine(I)-based variants.97 Inspired by the reflections above, we would like to systematically investigate the electronic and structural nature of XB in hypervalent halogen (III) systems. Compared with conventional Lewis acids in XB complexes (commonly based on monovalent halogen (I) salts), hypervalent halogen (III) compounds possess several distinct features: (1) halogen (III) compounds are cationic, allowing for stronger binding owing to the improved electrostatic affinity; (2) the presence of two mutually perpendicular electrophilic axes in halogen (III) compounds makes it possible to establish extended framework. In this chapter, a series of stable hypervalent iodine (III), bromine (III) and chlorine (III) salts have been synthesized (see Figure 2.1). For a simple spectroscopic setup, iodide, bromide, chloride, and trifluoromethanesulfonate were chosen as the counterions. Diphenyleneiodoniums (DPEI), diphenylenebromoniums (DPEBr), diphenylenechloroniums (DPECl) were prepared to compare the effects of different halogens in electron acceptors. The comparison between 28 diphenylenehalonium (DPEX, X represents Cl, Br, I, respectively) and diphenylhalonium (DPX, X is Cl, Br, I, respectively) species is particularly intriguing due to their similarity of chemical formula but significant difference in symmetry. The more rigid structure of DPEX salt is predicted to have significant π contributions in the formed XB; this effect may be dramatically mitigated in DPX cationic species. Given that orbital matching is particularly important in forming effective π bonds, evaluating the degree of covalency in mixed halogen/halide systems will be particularly revealing. To our best knowledge, the diphenylbromonium (DPBr) and diphenylchloronium (DPCl) are relatively unstable and rare references have reported the synthetic methods of the two complexes. Hence, only diphenyliodonium (DPI) was prepared for comparison with DPEX salts. Figure 2.1 A list of investigated hypervalent halogen (III) compounds. 29 2.1 Physical Properties of Hypervalent Halogen (III) Complexes During the preparation of those hypervalent halogen (III) complexes, some physical properties have been analyzed, including the trend of solubility and the stability in different states, which may be related to the electronic or geometric characteristics of such compounds. 2.1.1 Solubility DPEX halides (DPEX-X, X stands for Cl, Br, I) were synthesized from DPEX triflate (DPEX-OTf) using anion exchange method as mentioned in section 2.5. DPEX-X are much less soluble in polar solvents (e.g., water, methanol, acetonitrile) than DPEX-OTf. Therefore, the formed DPEX-X precipitated out from the mixture of DPEX-OTf and halide salt solutions. According to the reaction conditions and anion exchange yields as described in section 2.5, the solubility comparison of all DPEX-X compounds is shown in Fig. 2.2. In contrast to DPEI series, DPI halide (DPI-X) salts show opposite trend of solubility in common polar solvents. The solubility decreases from DPI-Cl to DPI-Br to DPI-I, which performs exactly the same as silver cation. Considering that the ionic bonds are more vulnerable than covalent bonds in polar solvents, the solubility trend may imply the different dominant contributions (electrostatics-dominant or covalency-controlled) to XB interactions in the two systems. 30 Figure 2.2 Top: The solubility comparison of DPEX series in polar solvents; Bottom: The solubility comparison of DPI series in polar solvents. Unlike many cation/anion pairs, DPEX-X and DPI-X series are slightly soluble in methanol or water (Note: the solubility of DPI-X is a bit better than DPEI-X in polar solvents). It suggests that the strong interactions between cationic and anion moieties or the π-π interactions among the aromatic systems are indestructible by the surrounding solvent molecules. 2.1.2 Stability It is reported that the stability of cationic iodine (I) complexes is generally low, which has impeded their widespread use.98 The stability of hypervalent halogen (III) system is thus of great concern, especially when it comes to the handling strategy during characterization and the practicability in real applications. 1H NMR spectroscopy has been utilized to study the stability of the hypervalent halonium (III) salts. DPI series in solutions DPI-Cl was chosen as the test sample in DPI series. About 5 mg of DPI-Cl compound was fully dissolved in 0.75 mL deuterated dimethyl sulfoxide (DMSO-d6) before the first test. Then the tested NMR tube was placed in the fume hood at ambient 31 environment for 20 days before the second test. As shown in Fig. 2.3, there are negligible differences between the spectra before and after 20 days, indicating its tolerance to air and water. Figure 2.3 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPI-Cl and DPI-Cl after 20 days. DPEI series in solutions DPEI-X samples were tested using the same method before and after 20 days. No significant changes of 1H NMR spectra were observed. DPEBr series in solutions DPEBr-Cl was examined before and after 20 days. Chemical shifts and their corresponding multiplicity remained unchanged except for the most downfield one. The most de-shielded peak represents the proton at H1 position (as labelled in Figure 2.4) The chemical shift decreases, showing a more shielded environment around H1. This might be caused by the changes of the surrounding solvent molecules, since the dimethyl sulfoxide (DMSO) is highly hygroscopic, and the water content will largely increase after 20 days. The reason why only the H1 shows the significant change is still unclear. 32 Figure 2.4 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPEBr-Cl and DPEBr-Cl after 20 days. In contrast, DPEBr-Br has no visible changes before and after 25 days, which confirms its stability at ambient environment. Figure 2.5 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of fresh DPEBr-Br and DPEBr-Br after 25 days. DPECl series in solutions DPECl systems have demonstrated a relatively lower stability than DPEBr, DPEI, and DPI series. DPECl-Cl in solution can remain stable at ambient environment for 33 one day, but it will start decomposition slowly. As displayed in Figure 2.6, the impurity peaks in the range of 6.7-7.7 appear in DPECl-Cl solution after 10 days. The impurity was initially assumed to be the decomposed aromatic products induced by visible light. It is hypothesized that the decomposed products could be 2-chloro-1,1'-biphenyl and its derivatives. Then a control experiment was carried out, in which the DPECl-Cl sample tube was wrapped up with aluminum foil for 10 days. The decomposition still occurred to a large extent; therefore, the reason for the decomposition might be the slow reaction with water or the solvent DMSO or the oxygen from air. Figure 2.6 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of DPECl-Cl under different conditions. Similar phenomena occurred in all other tested DPECl samples (i.e., DPECl-OTf, DPECl-Br, and DPECl-I). In other words, such decomposition is typical in DPECl series, which is attributed to the volatility of C-Cl bond compared to the more stable C-Br and C-I bonds in hypervalent halogen (III) systems. 34 Handling strategy In summary, the hypervalent complexes under investigation are quite stable under ambient conditions - except for certain chloronium species, which are somewhat moisture, oxygen, and light sensitive. All of the hypervalent complexes in solid states can stay stable for at least a month. To avoid undesired decomposition, the synthesized samples were degassed, refilled with nitrogen and transferred into the glovebox freezer before the scheduled beam time (Note: the XAS experiment performed on the prepared samples will be carried out during beam time, therefore a proper storage strategy is required to avoid sample decomposition). If decomposition has already occurred, solvent wash method can help to get rid of the decomposed impurities. Considering the low solubility of hypervalent complexes in common solvents (e.g., toluene, diethyl ether, acetonitrile, methanol etc.), the decomposed aromatic products can be flushed away by those common solvents while the samples themselves stay as solids. For example, some of the DPECl-Br powders were found decomposed according to the NMR spectra. The solid samples were subsequently washed with the mixture of toluene and acetonitrile for five times. After vacuum filtration and high-pressure drying, the solid sample was re-dissolved in deuterated solvent for 1H NMR test. In the new NMR spectrum, the impurity peaks completely disappeared (see Figure 2.7). 35 Figure 2.7 The 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectral comparison of DPECl-Br with decomposition and after solvent wash process. 2.2 Crystal Structures of Hypervalent Halogen (III) Complexes Single crystal XRD is a very powerful tool to provide unequivocal electron distribution and structural information of investigated molecules. It gives not only the connectivity patterns of atoms but also the preferred packing orientations in the crystalline materials.99 The obtained XRD result also allows for a clear prediction of geometric properties, especially in solid states. In this section, single crystal XRD was used to study the crystal structures of hypervalent complexes. All the detailed information of XRD data is provided in Appendix C. 2.2.1 Crystal Structures of DPI Series Basic structure Solid-state molecular structures of complexes in the DPI series are displayed in Figure 2.8, with important geometric parameters listed in Table 2.1 and detailed X-ray diffraction information presented in Appendix C. The structural information of DPI-OTf was adapted from reference,100 and other crystal structures were experimentally determined. For a clear demonstration, all the hydrogen atoms in the crystal structures are omitted. Similar to a standard XB module, the I+∙∙∙X- (X represents O, Cl, Br, I, respectively) interaction length in each case is 36 significantly shorter than the sum of Van der Waals radius and the C−I+∙∙∙X- angle falls into the typical range of a XB bond angle (~170° − 180°). Interestingly, each X anion is coplanar with one of the iodobenzene systems, which indicates the possibility of π-electron communication between the two moieties. Figure 2.8 View of the solid-state molecular structure of each of the species. The grey atoms are carbon atoms; the red ones are oxygen atoms; the purple ones are iodine atoms; the yellow ones stand for sulfur; the brown atoms are bromine; the green ones represent chlorine; the light green atoms are fluorine. 37 Table 2.1 The important parameters of the formed XBs in DPI series. DPI-OTf DPI-Cl DPI-Br DPI-I X−I1 bond length (Å) * 2.895 3.074 3.226 3.412 X−I1 bond length / sum of rw* (%) 82.71 82.41 84.23 86.16 X−I1−C1 angle (°) * 176.15 177.64 178.73 177.36 X−C1−C2−C3 dihedral angle (°) * 178.00 179.49 179.07 176.53 * X stands for O, Cl, Br, I, respectively. Dimer Considering that both of electron donors (i.e., halides and triflate) and acceptors (DPI moiety) can form at least two interactions, more extended architectures are anticipated. As shown in Figure 2.8, self-assembling dimer structures are observed in a centrosymmetric module in all DPI complexes. The dimer topologies stand out with several distinct features: (1) every phenyl ring is parallel to its centrosymmetric counterpart. (2) Each anion or DPI moiety is simultaneously involved in two XB interactions with slightly different bond lengths. In terms of the XB bond lengths, DPI-Br and DPI-OTf dimers are more symmetric than DPI-Cl and DPI-I ones. (3) Each halide binds to two DPIs with a single atom while the triflate anion interacts with two hypervalent iodine atoms via different oxygen atoms. Consequently, the two hypervalent iodine atoms and two halides at the center of the dimer structure lie on the same plane, but the two hypervalent iodine atoms and the four interacting oxygen atoms in DPI-OTf system form a stepped geometry instead. (4) The aromatic system is not only coplanar with the halogen-bonded halides or oxygens, but also nearly coplanar with those non-interacting ones. For instance, Cl1 atom is halogen bonded with the top DPI moiety but not with the bottom DPI as shown in Figure 2.9. However, the Cl1−C1−C2−C3 dihedral angle is close to 180°, which is also observed in the other DPI systems. In such case, an expanded planar system can be established via those halogen-bonded and non-38 interacting anions. (5) Another obvious pattern in Figure 2.9 is that two vicinal DPI moieties can interact via π-π stacking. According to the π-π interaction lengths as labelled in green in Figure 2.9, the interactions are stronger in DPI-Cl and DPI-Br systems relative to those in DPI-I and DPI-OTf ones, which may be attributed to the steric hindrance of those counterions. The existence of such π-π interactions and the characteristics described in (4) give rise to a periodic layered architecture where two extended planar systems are parallel to each other. Figure 2.9 The snapshots of some special geometries in the DPI crystal packings. For each scheme, the left picture stands for the front view, and the right picture represents the left view. The π-π interaction lengths are labelled in green beside the green dash line (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). 39 Disorder There is significant disorder in the crystal packing in the DPI series. Taking DPI-Cl as an example, it contains major (drawn in solid lines) and minor (drawn in dash lines) disorders on the phenyl rings as displayed in Figure 2.10. To avoid confusion, the aforementioned DPI structural information is merely based on the major disorder. Even with the disorder present, there’s still a small void in the structure. Therefore, inefficient packing of the structure may allow the DPI fragment to rotate around iodine, thus forming a slightly unfavorable minor structure. Another possible reason could be the orbital overlap and size mismatch, which may induce energetically similar conformers. From Table 2.2, the minor disorders are formed on both phenyl rings of DPI-Cl, but only on one of them in DPI-I and DPI-Br. The larger halides may lead to more compact crystal packings. Figure 2.10 Crystal structure of DPI-Cl complex (both major and minor disorders are included). The probability is 50%; The temperature is 173 K. 40 Table 2.2 Comparison between major and minor disorders in four DPI complexes DPI-OTf* DPI-Cl DPI-Br DPI-I I1-C1 bond length (Å) 2.169 2.118 (2.053) 2.128 (2.128) 2.141 (2.141) I1-C7 bond length (Å) 2.117 2.069 (2.137) 2.100 (2.119) 2.108 (2.098) C1-I1-C7 angle (°) 95.15 92.6 (89.6) 93.0 (91.9) 94.4 (92.0) * The crystal structure of DPI-OTf was adapted from reference,100 and the information of minor disorder is not available. The numbers in parentheses are the structural parameters of the minor disorder. 2.2.2 Crystal Structure of DPEI Series Basic structure Unlike the DPI series, the DPEI complexes possess a more rigid skeleton, where the extra C−C bond has fixed the two rotating phenyl rings into the same plane and thus significantly changes the energetic and electronic properties of the system. In the simplest molecular unit, XB interactions between the hypervalent iodine and counterions are shown in Fig. 2.11, and the XB-related parameters are listed in Table 2.3. XB interaction lengths are all shorter than the sum of the corresponding Van der Waals radius, and the X−I1−C1 angle falls into a reasonable range (~170° − 180°) except for DPEI-OTf. Besides, the directionality of XB holds all the interacting atoms on the same plane. When compared with DPI series, DPEI systems have a slightly shorter XB bond length but a relatively worse linearity. A closer contact is expected between a larger aromatic system and the counterion. However, the directionality is somewhat sacrificed due to the lack of flexibility in DPEI moiety. 41 Figure 2.11 View of the solid-state molecular structure of each of the species. (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). Table 2.3 Important parameters of the formed XBs in DPEI series. DPEI-OTf DPEI-Cl DPEI-Br DPEI-I X−I1 bond length (Å) 2.774 3.030 3.170 3.375 X−I1 bond length / sum of rw* (%) 79.26 81.23 82.77 85.23 X−I1−C1 angle (°) 166.58 171.89 172.99 173.18 X−C1−C2−C3 dihedral angle (°) 178.38 177.83 178.21 178.05 * rw means the corresponding Van der Waals radius. Dimer Similarly, the potency of the two binding sites on both electron donor (Cl-, Br-, I-, OTf-) and acceptor (DPEI) has been fully exerted in the crystal packing. Dimer structures were also established in DPEI-X systems (see Figure 2.11). Each DPEI interacts with two different halides simultaneously, and vice versa. The formed dimer geometry is highly symmetric and planar in either DPEI-Cl or DPEI-Br system with DPEI-I being slightly asymmetric, perhaps due to a larger size of iodide. Surprisingly, the architecture of DPEI-OTf crystal is quite different from the style described above. Each DPEI (or triflate) interacts with two triflates (or two DPEIs) via two XBs 42 with slightly different strengths. However, the large steric hindrance of triflate ion has impeded the formation of a dimer structure; the zig-zag topology is generated instead where DPEI and OTf alternate in the chain. 2D architectures The highly planar and symmetric dimer structures of DPEI-X periodically recur, thus forming an extended 2D framework. DPEI-Cl was taken as an example in Figure 2.12. The dimer units are connected end to end, thus forming an infinite planar strip. The self-assembling strips will stack on each other via π-π interaction as shown in Figure 2.13. The aromatic systems of the top DPEI-Cl and the bottom ones are highly overlapped, nevertheless they have taken the opposite orientation. The stacking pattern of DPEI-Br is very similar to that of DPEI-Cl, in which the π-π distance is as short as 3.676 Å. Due to the asymmetry of DPEI-I complex, the stacking structure is a bit different from DPEI-Cl and DPEI-Br. The overlapping area between the top and bottom diphenyleneiodonium is smaller in DPEI-I than DPEI-Cl, yet the π-π interaction length is much shorter than that of DPEI-Cl. Such π-π interactions also present in DPEI-OTf system but with relatively longer distances. Figure 2.14 provides a broader view of the layered structure in DPEI-X systems. The strip structures were stacked vertically in DPEI-Cl and DPEI-Br adducts, while they piled on each other to form tilted packings in DPEI-I complex. 43 Figure 2.12 2D architectures of DPEI-Cl system. Top view, front view and left view are shown, respectively (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). Figure 2.13 The stacking patterns of DPEI-Cl (left) and DPEI-I (right) (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). Figure 2.14 The front view of DPEI-Cl and DPEI-I systems (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). 44 2.2.3 Similarity and Difference between DPI and DPEI Series In a conventional XB construction, the uneven distribution of electron density on the halogen atom gives rise to two kinds of interactions. The typical XB is formed at the elongation of R−X bond, meanwhile the resulted electron-rich “belt” attracts electrophiles perpendicular to the XB axis. Herein, the hypervalent scaffold (DPI and DPEI) effectively alleviates the amphoteric character of the covalently bonded iodine. The two nearly perpendicular C−I bonds have blocked the formation of the electron “belt”, instead two electron-deficient regions are generated as XB active sites. The presence of two mutually perpendicular electrophilic axes in X(III) compounds makes it possible to form an extended delocalized framework. Halide, as a counterion, can be a multidentate electron donor since it possesses 4 lone pairs. Triflate contains three oxygen atoms in the sulfonyl group, which can also work in multidentate modules. Electron acceptors and donors with more than one binding sites allow for various hierarchical architectures. However, there are many factors that can influence the structures in solid states. For instance, the difference in geometric rigidity has played a crucial role in the established crystal structures. The comparison between DPEI and DPI systems is illustrated in Figure 2.15, where four building blocks are examined. In DPI-X systems, 52 atoms could be held onto the same plane, while up to 88 atoms can be fixed on the same plane in DPEI-X complexes. DPEI series have maintained all the interacting moieties (DPEI and halide atoms) on the same plane, thus a highly organized 2D architecture is established. Since the other phenyl groups (i.e., the ones not drawn in Figure 2.15) are out of the 52-atom plane, a more disordered 3D framework is formed in DPI-X compounds. In addition, the planarity of DPI-X system is not as good as that of DPEI-X. This may account for the better solubility of DPI-X in polar solvent than DPEI-X because it is easier for the solvent molecules to break into the less ordered 3D framework of DPI-X. 45 Figure 2.15 The comparison of the planar structures in DPI-halide and DPEI-halide systems. The crystal structure of DPEI-X is fascinating since the ordered layering architecture is similar to graphite which possesses excellent electronic and mechanical properties. However, the structure of DPEI-X is different from graphite in several aspects: (1) graphite consists of layers of carbon atoms arranged in a honeycomb structure.101 Graphene layers are closely stacked via π-π interactions in graphite, similar to DPEI-X. Nevertheless, the structures of each layer in the two systems are different. Graphene sheet is composed of pure carbon atoms that are connected by covalent bonds, while DPEI-X layer is established by both covalent bonds and XBs. The involvement of weak interactions has provided more possibilities in the design of responsive supramolecular assemblies due to the flexibility and reversibility of weak interactions. In addition, the layered structure in DPEI-X is heteroatomic, which can largely improve the versatility of such framework. Complicated treatment is usually necessary to accomplish heteroatom doping in graphene for improved electrochemical, geometrical and optical properties.102 Unlike graphene, the electronic properties of DPEI-X system can be easily tuned using anion exchange methods as 46 described in section 2.5. (2) Different from the extended planar structure in graphene, DPEI-X possesses strip-like topology in each layer. The strip is extended in merely one direction rather than two dimensions, which has endowed this system with better directionality and selectivity than the isotropic graphene sheet. 2.2.4 Crystal Structures of DPEBr Series Basic structure Similar to the structure of DPEI series, DPEBr compounds manifest the typical XB-module (Figure 2.16). The detailed structural information of each species is listed in table 2.4. The X−Br1 bond lengths are all shorter than the sum of Van der Waals radius, and the XB angles fall into the range of 170º−180º. Compared to DPEI series, the XB angles in DPEBr series are closer to 180º. In particular, DPEBr-Br has a straight XB angle and the highest planarity. Figure 2.16 View of the solid-state molecular structure of each of the species. (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). 47 Table 2.4 Important parameters of the formed XBs in DPEBr series. DPEBr-OTf DPEBr-Cl DPEBr-Br DPEBr-I X−Br1 bond length (Å) 2.773 2.988 3.132 3.355 X−Br1 bond length/sum of rw* (%) 82.28 83.00 84.65 87.60 X−Br1−C1 angle (°) 173.40 176.78 179.64 176.64 X−C1−C2−C3 dihedral angle (°) 179.50 176.81 179.91 177.07 * rw means the corresponding Van der Waals radius. Dimer The planar dimer structure is also observed in DPEBr-X series. Each halide interacts with two DPEBr moieties simultaneously, meanwhile each DPEBr binds to two halides via two XBs with slightly different bond lengths. Due to the large steric hindrance, triflate anion is not capable of forming such dimer structure, instead a stepped geometry is established as shown in Figure 2.16. 2D architectures The stacking pattern is also found in DPEBr-X crystals. DPEBr-Br and DPEBr-I have similar 2D constructions to the DPEI-I system, where the extended planar sheets are parallel to each other and stacking together via π-π interaction. However, in DPEBr-Cl complex, each delocalized planar sheet is only parallel to the ones above and below it but not to those on the left and right. Figure 2.17 The stacking patterns of DPEBr-X systems (C: grey; O: red; F: light green; S: yellow; Cl: green; Br: brown; I: purple). DPEBr-Cl DPEBr-Br DPEBr-I48 2.3 Electronic Structures of Hypervalent Halogen (III) Complexes To investigate the electronic details of those hypervalent halogen (III) complexes, NMR, XAS and computational methods have been deployed. 2.3.1 NMR Results NMR is one of the most powerful techniques in laboratory, which has been widely applied in molecular identification, food science and medical diagnosis.103–105 One of the most important functions of NMR is the ability to reveal the chemical environment around the elements of interest and thus provide useful information about their electronic structures.106 In this section, 1H and 13C NMR results of DPI and DPEX series are presented, which were prepared in deuterated dimethyl sulfoxide (DMSO-d6) solvent with roughly equal concentration (~ 0.01 g/mL). (The 13C NMR results are provided in Appendix C). In the following discussions, the NMR spectra of triflate salts is chosen as the contrast, ∆δ is considered as the difference of chemical shift between the DPEX-X and DPEX-OTf (or between DPI-X and DPI-OTf) for each proton. In DPI-X series (Figure 2.18), all characteristic NMR chemical shifts (δ) in DPI-X move to upfield (lower ppm) compared to DPI-OTf, indicating a more shielded environment after binding with halides. In contrast, the δ values of Ha, Hb and Hc in DPEI-X (Figure 2.19) decrease if compared to those in DPEI-OTf, while only Hd is deshielded. The spectral differences between the two series might be attributed to the following reasons: (1) the mechanism of XB interactions in the two series are dissimilar. In DPI-X, the formation of XB has dramatically influenced the diamagnetic ring current (i.e., the π electron effects in the aromatic rings), therefore all chemical shifts of the aromatic hydrogens are shifted to the same direction. This could be achieved by either forming π-type XB with halides or anion-π interaction. It is more likely that the presence of halides in DPEI-X has mediated the electronic environment of the aromatic hydrogens by acting on the C−I bond rather than directly 49 affect the whole aromatic system. (2) The binding modes in the NMR tests are more complicated compared to those in the crystal structures. The final spectrum is an averaged reflection of all possible situations. (3) Hydrogen bonding may also exist between the counterion and Ha (or Hd). The halides may even form hydrogen bonding with Ha and halogen bonding with iodine (III) simultaneously, which can lead to the different behavior of each proton in DPEI-X. (Note: Ha and Hd in the peak assignment are indeterminate) Since the powders were dissolved in solutions using DMSO- d6 as solvent, more factors should be considered, such as concentration and solvation effect. In addition, weak interactions, including XB, anion-π interaction, are dynamic in solution (i.e., constantly forming and breaking), making it even more difficult to analyze. Figure 2.18 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPI-X series. 50 Figure 2.19 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEI-X series. DPEBr-X and DPECl-X series (see Figure 2.20 and 2.21) follow the same trend as DPEI-X, in which the peaks of Hd move to downfield, but Ha, Hb and Hc shift to the opposite direction. However, the spectral change is more noticeable in DPEI-X than DPEBr-X and DPECl-X. If DPEX-OTf (or DPI-OTf) is chosen as the reference and the chemical shift change (Δδ) is defined as the difference of δ in halide and triflate system, Δδ is increasing from iodide to bromide and chloride. Both findings may be explained by the higher polarizability of iodine atom. Figure 2.20 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEBr-X series. 51 Figure 2.21 1H NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPECl-X series. 2.3.2 XAS Analysis 2.3.2.1 Theories of XAS Techniques XAS is a type of element-specific experiment under X-rays with definite energy. Some of those high-energy photons will be absorbed by the sample, enabling the excitation or ejection of the core electrons in the atoms. There are three common ways of quantifying the absorption intensity: (1) transmission mode, which is similar to the mechanism of typical UV-Vis spectroscopy; (2) fluorescence mode, in which the photon signal given off by the excited atom after an electron falls into the core hole is collected (the core hole is generated once the core electron is excited or ejected); (3) Auger electron mode, in which the total ejected electron yield is measured as the core hole is filled. In this thesis, all the XAS experiments were carried out using the fluorescence mode as it is advantageous when samples are of low concentrations. In such mode, the absorption coefficient is proportional to the ratio of the measured fluorescence intensity and the incident intensity.107 52 To better explain XAS spectra, some important terminologies will be clarified up front. An exemplary graph of tetrabutylammonium bromide solid sample is shown in Figure 2.22. First of all, the “K-edge”, “L-edge” are used to identify the core holes in a given spectrum. “K-edge” means the excitation of electrons from the n=1 shell, while “L” stands for the n=2 shell. “Edge” itself has not yet been unequivocally defined, but it is often referred to the sudden rise of signal intensity. The energies above the edge will eject the core electron as photoelectron. The peak right after the sharp rise is often termed the “white line” or “edge peak”. Any peak or shoulder before the edge jump is called “pre-edge”. “E0” is the corresponding energy at the steepest inflection point on the spectrum. In convention, “peak intensity” represents the area underneath a peak instead of the peak height since the peak area is directly proportional to the probability of corresponding transitions. All the features near or on the edge is called “X-ray absorption near-edge structure” (XANES, it commonly ends at 30 - 50 eV after E0), while the oscillations immediately following the XANES region is called “extended X-ray absorption fine structure” (EXAFS). In this thesis, we mainly focus on the XANES region to gain the information on charge transfer in weak interactions. 53 Figure 2.22 An exemplary XAS graph of tetrabutylammonium bromide solid sample. Spectrum was collected in SSRL. Electron donation from a Lewis base to a Lewis acid creates hole density on the base, generating a partially empty orbital in the donor atom that can be monitored through core-electron transitions. For example, the first electric dipole allowed transition for a chloride ion is from Cl1s orbital to Cl4p, since Cl4p is the lowest empty or half-empty orbital. Electrostatics between a chloride ion and its XB partner would only change the relative energies of the Cl orbitals as shown in Figure 2.23 (a), then we would only see a shift of edge in the spectrum after the formation of XB. Charge transfer interactions between the XB pairs would cause orbital mixing of the valence Cl3p orbitals and an acceptor orbital, thus forming a low-lying empty σ*XB orbital and a newly-allowed excitation (σ*XB ← Cl1s) (see Figure 2.23b). In this case, a pre-edge feature would appear in the spectrum. The intensity of the new peak is proportional to the amount of Cl3p character mixed in the new orbital σ*XB, which enables us to directly measure the charge transfer component in a XB. 54 Figure 2.23 A molecular orbital diagram depicts the transitions of the core electrons within different models: (a) electrostatic model only; and (b) with inclusion of charge transfer/covalency. 2.3.2.2 XAS Results The Cl K-edge XAS spectra of DPI-Cl, DPEI-Cl, DPEBr-Cl are compared in Figure 2.24. There exist two distinct pre-edge features at around 2816.0 − 2817.5 eV and 2818.0 − 2819.0 eV, respectively (Note: The Cl K edge jump in this thesis is calibrated to 2820.2 eV). This is different 55 from the previously reported systems where only one pre-edge feature showed up.16,34 It indicates that at least two kinds of covalent components are present in these hypervalent systems. Figure 2.24 Cl K-edge XAS spectra of DPEI-Cl, DPI-Cl, DPEBr-Cl. BlueprintXAS software was used to quantify the pre-edge feature in each spectrum. It is a matlab-based program developed to fit XAS spectra, especially for XANES region. It relies on a Monte Carlo approach to choose parameters without bias when simultaneously fitting background and edge features.108 Figure 2.25 was given as a fitting example, in which background, edge peak and pre-edge feature were simulated within a pre-specified range. Since the XANES region is our focus in this thesis, an appropriate fitting of the near-edge range is accepted. The fitting results are summarized in Table 2.5. The estimated total charge donation is substantial, which is much higher than the conventional XB compounds (~10%)16 and analogous to some coordination complexes (6% − 22%)109. 56 Figure 2.25 An exemplary graph showing how BlueprintXAS fits the given data. Table 2.5 A summary of fitting results in DPI-Cl, DPEI-Cl, and DPEBr-Cl systems. entry pre-edge energy (eV) normalized pre-edge intensity %Cl3p total charge donation* DPI-Cl 2817.11 ± 0.03 2818.43 ± 0.07 1.2 ± 0.1 0.9 ± 0.1 15.0 ± 1.5 DPEI-Cl 2817.13 ± 0.00 2818.33 ± 0.03 1.3 ± 0.1 0.8 ± 0.1 14.8 ± 1.3 DPEBr-Cl 2817.27 ± 0.01 2819.14 ± 0.04 1.1 ± 0.1 1.0 ± 0.2 15.2 ± 1.3 * Total charge donation is calculated in comparison with Cl K-edge XAS data on a CuCl42- reference; the percent covalency is confirmed to be proportional to the intensity of pre-edge feature after normalization. The conversion coefficient is the same as the reference.16 57 2.3.3 Computational Investigations 2.3.3.1 DFT Calculations to Find Out the Representative Unit To gain more details of the covalent contributions in XBs, computational methods were employed. The first step is to find out the smallest and most representative unit of each XB complex. DFT calculation is one of the most prevailing methods of modelling the electronic and geometric properties of many-body system (especially for ground-state system) based on its spatially dependent electron density.110 The monomer and dimer structures of DPI and DPEI series have been optimized using DFT calculations (The details of the DFT calculation are described in section 2.5.3). As shown in Figure 2.26 and Table 2.6, the predicted structural information (Cl1−I1 bond length in particular) of DPI-Cl monomer is quite different from those in XRD results. However, the crystal structure can be well simulated using the optimized dimer geometry of DPI-Cl. The DFT-calculated dimer structure has not only successfully presaged the formation of asymmetric halogen bonding, but also produced accurate parameters when compared with the experimental results. Similar trends have also been observed in DPI-Br and DPI-I series (see Table 2.7 and Table 2.8). Figure 2.26 A structural snapshot of DPI-Cl system generated from XRD and DFT results (C: grey; Cl: green; I: purple). 58 Table 2.6 A summary of structural information of DPI-Cl system generated from XRD and DFT results. DPI-Cl (XRD) DPI-Cl (DFT-monomer) DPI-Cl (DFT-dimer) Cl1−I1 bond length (Å) 3.074 (3.118)* 2.673 3.028 (3.031) Cl1−I1−C1 angle (°) 177.64 175.93 176.30 Cl1−C1−C2−C3 dihedral angle (°) 179.49 179.42 179.45 C1−I1−C7 angle (°) 96.42 89.64 92.00 * The number in the paratheses is the other XB bond length in the dimer structure. Table 2.7 A summary of structural information of DPI-Br system generated from XRD and DFT results. DPI-Br (XRD) DPI-Br (DFT-monomer) DPI-Br (DFT-dimer) Br1−I1 bond length (Å) 3.226 (3.237) 2.840 3.177 (3.182) Br1−I1−C1 angle (°) 178.73 176.11 176.23 Br1−C1−C2−C3 dihedral angle (°) 179.07 179.39 179.79 C1−I1−C7 angle (°) 93.01 89.22 91.20 Table 2.8 A summary of structural information of DPI-I system generated from XRD and DFT results. DPI-I (XRD) DPI-I (DFT-monomer) DPI-I (DFT-dimer) I2−I1 bond length (Å) 3.412 (3.451) 3.065 3.381 (3.385) I2−I1−C1 angle (°) 177.36 176.44 176.84 I2−C1−C2−C3 dihedral angle (°) 176.53 179.25 179.40 I2−I1−C7 angle (°) 94.39 88.83 90.65 59 In terms of DPEI-X systems, the calculated dimer structures can also decently model the crystal structures. Taking DPEI-Cl adduct as an example (see Figure 2.27 and Table 2.9), the predicted Cl1−I1 bond lengths are almost the same as the ones in the crystal form. In addition, the planarity of the dimer unit has also been anticipated. In conclusion, the dimer structure is the most characteristic and representative unit in these two hypervalent models. Figure 2.27 A structural snapshot of DPEI-Cl system generated from XRD and DFT results (C: grey; Cl: green; I: purple). Table 2.9 A summary of structural information of DPEI-Cl system generated from XRD and DFT results. DPEI-Cl (XRD) DPEI-Cl (DFT-monomer) DPEI-Cl (DFT-dimer) Cl1−I1 bond length (Å) 3.030 2.659 3.032 Cl1−I1−C1 angle (°) 171.89 170.09 170.90 Cl1−C1−C2−C3 dihedral angle (°) 177.83 179.85 179.92 60 Table 2.10 A summary of structural information of DPEI-Br system generated from XRD and DFT results. DPEI-Br (XRD) DPEI-Br (DFT-monomer) DPEI-Br (DFT-dimer) Br1−I1 bond length (Å) 3.170 2.828 3.184 Br1−I1−C1 angle (°) 172.99 171.39 171.75 Br1−C1−C2−C3 dihedral angle (°) 178.21 179.96 179.90 Table 2.11 A summary of structural information of DPEI-I system generated from XRD and DFT results. DPEI-I (XRD) DPEI-I (DFT-monomer) DPEI-I (DFT-dimer) I2−I1 bond length (Å) 3.375 (3.393) 3.055 3.389 (3.390) I2−I1−C1 angle (°) 173.18 172.81 173.15 I2−C1−C2−C3 dihedral angle (°) 178.05 179.96 179.90 Gibbs free energy analysis was then implemented for the optimized dimer structures of DPI-Cl, DPEI-Cl, and DPEBr-Cl adducts. The definition of ∆Gf is shown below (Equation 1). The calculated formation energies (∆Gf0) and the experimentally resolved charge donation are listed in Table 2.12. The comparison in the table again confirms that the degree of charge transfer is not necessarily proportional to the formation energy of XB. Notably, the calculated binding energy of XB in each hypervalent halogen (III) system is higher than common HBs (usually in the range of 0.2 − 40 kcal/mol).10 ∆𝐺! = [#!"#$%$(#&'(")* ' #&+,)%"!$)∗*], ( 1 ) 61 Table 2.12 Calculated ∆Gf 0 and spectroscopically resolved results in the studied systems DPI-Cl DPEI-Cl DPEBr-Cl ∆Gf 0 (formation energy of XB) (kcal/mol) -50.5 -55.6 -52.2 %Cl3p total charge donation 15.0 ± 1.5 14.8 ± 1.3 15.2 ± 1.3 2.3.3.2 TD-DFT Simulations to Probe the Covalent Contributions Since we have figured out that the dimer is the most representative building block in each hypervalent adduct, the dimer unit was then used to simulate XAS data using TD-DFT methods. TD-DFT is a more complete formalism of DFT calculation, which is mainly used to investigate the dynamics of many-body systems under time-dependent potentials, like electric or magnetic fields.111 Therefore, it is often applied to simulate absorption spectra and excited states. Herein, DPI-Cl, DPEI-Cl, DPEBr-Cl complexes have been studied using TD-DFT. The simulated graphs are shown in Figure 2.28 and 2.29. On the left graphs, the important σ*(R-X⟵Cl-) Kohn−Sham acceptor orbitals (i.e., solutions from Kohn−Sham theory) are inserted to those intense transitions. The transitions are visualized as electron density difference map (EDDM) on the right graph. EDDM is calculated to show the changes of a molecule when it changes state or the relative positions of its atoms.112 The advantage of EDDM is that it has provided a more intuitive visualization of the difference between ground state and excited state for each transition. All systems are predicted to have two pre-edge features with about 1 - 2 eV apart from each other, meanwhile the first pre-edge is significantly higher than the second one. These characteristics align well with the spectroscopic data in section 2.3.2.2. The predicted transitions in DPEI-Cl and DPEBr-Cl are relatively straightforward. The first pre-edge peak contains two distinct transitions from Cl1s orbital to σ*(R-X⟵Cl-) orbitals generated by Cl3p orbitals and σ* orbitals of DPEX moieties. 62 The second peak comes from the transition from Cl1s orbital to σ*(R-X⟵Cl-) orbitals formed by Cl3p orbitals and σ bonding orbitals of two DPEX moieties. Figure 2.28 TD-DFT simulations of DPEI-Cl and DPEBr-Cl complexes. The inserted pictures in the left graph are visual representations of the important σ*(R-X⟵Cl-) Kohn−Sham acceptor orbitals for each hypervalent salt (isovalue is 0.03 for DPEI-Cl and 0.02 for DPEBr-Cl); the inserted pictures on the right graph are the electron density difference maps for the corresponding transitions (isovalue is set as 0.001). A constant linear shift was applied to the calculated energies to match experimental energies.113 63 The predicted spectrum of DPI-Cl is more complicated than DPEX-Cl systems. The first pre-edge feature indicates two σ-manner XB interactions similar to those in DPEX-Cl complexes. It is intriguing that the second feature involves both σ and π interactions. Taking the Kohn−Sham acceptor orbitals as example, the chloride atom interacts with one phenyl ring through σ interaction and simultaneously communicates with the other centrosymmetric phenyl group via π interaction. In the EDDM, we can also observe that the joint iodine atom is working as a “transfer station”, communicating with the top phenyl ring through σ-type interaction and the bottom ring with π-type delocalization. Therefore, we can conclude that the chloride herein plays an important role in mediating both σ- and π-type charge transfer. The orbital difference between DPI and DPEX corresponds to what have been observed in NMR spectra: the involvement of π-type delocalization in DPI has influenced the diamagnetic ring current so that the chemical shifts of all protons move to upfield (see Figure 2.18). In other words, the environment of all protons is more shielded as partial electrons are donated from chloride into each aromatic system. In contrast, the Δδ in DPEI or DPEBr is not consistent for each proton, which is attributed to the pure σ interaction in DPEX series. The change of chemical environment around each nucleus comes from C-I σ bond instead of the ring current. 64 Figure 2.29 TD-DFT simulation of DPI-Cl complex. The inserted pictures in the left graph are visual representations of the important σ*(R-X⟵Cl-) Kohn−Sham acceptor orbitals for each hypervalent salt (isovalue is 0.02); the inserted pictures in the right graph are the electron density difference maps for the corresponding transitions (isovalue is set as 0.001). A constant linear shift was applied to the calculated energies to match experimental energies.113 2.3.3.3 Charge Decomposition Analysis to Study the Covalent Contribution Charge decomposition analysis (CDA) is a useful tool of examining the donor-acceptor interaction scheme, especially in the quantitative expression of Dewar–Chatt–Duncanson model.114 Herein, CDA was applied to investigate the degree of charge transfer from the halide center to the DPEX or DPI moiety. Each examined dimer complex was segmented into 4 different fragments (For example in Figure 2.8, each chloride is a part, each DPI is a part). The calculated charge donations are tabulated and compared to the XAS fitting results in Table 2.13. The calculated charge donation decreases slightly when the counterion changes from Cl to Br and I. The degree of charge transfer in DPI-Cl is very close to that in DPEI-Cl. It is confirmed in both CDA results and XAS fitting data, though the CDA analysis has estimated a relatively higher number than XAS fitting. 65 Table 2.13 Comparison of total charge donation from CDA analysis and XAS fitting Entry % Total donation from CDA* % Total donation from XAS fitting DPI-Cl-dimer 19.4 15.0 ± 1.5 DPI-Br-dimer 18.6 N.A. DPI-I-dimer 18.2 N.A. DPEI-Cl-dimer 21.0 14.8 ± 1.3 DPEI-Br-dimer 20.0 N.A. DPEI-I-dimer 19.5 N.A. * The total charge donation is considered as the sum of charge donation from each halide to the two interacting DPEI or DPI moieties. 2.4 Conclusion and Future Prospects In this chapter, a thorough investigation on XB interactions has been performed, in which several representative hypervalent halogen (III) compounds were chosen as model systems. The extended planar geometries in crystal structures may have important implications in material science. NMR and XAS studies, in combination with computational methods, have demonstrated the substantial covalent contributions in XBs among such ionic complexes. More importantly, XBs in these hypervalent systems have two distinct charge transfer components, which are quite different from the previously reported ones. DPI-Cl complex, in particular, has both σ- and π-manner interactions entangled between DPI and Cl counterparts. Considering the uniqueness of crystal structure and the capability of charge transport via XBs, such systems can be further developed in the future: (1) Different substituents attached to the 66 aromatic system are anticipated to modulate the electronic structures of induced XBs by altering steric hindrance or electron-donating/withdrawing ability of the cationic moiety. Different positions of substituents on the aromatic rings may also influence the properties of electron acceptor X(III). (2) Hypervalent halogens could also be mounted on both ends of the cationic moiety, in which case a large electron-delocalized framework is established as shown in Figure 2.30 (right). This is expected to be applied as a type of reversible and efficient molecular electronics. Figure 2.30 Proposed structures with different substituents (left) and with two hypervalent halogens in one cationic moiety (right). 2.5 Methods 2.5.1 Sample Synthesis All the starting materials were purchased from Sigma Aldrich or TCI and used without further purification. Synthesis of dibenzo[b,d]iodol-5-ium trifluoromethanesulfonate (DPEI-OTf) The synthetic method was adapted from the papers published by Olofsson and Huber (Figure 2.36).115–117 In a 100 mL round bottom flask, 1.25 g (4.46 mmol) of 2-iodo-1,1'-biphenyl (purity: 96%) was dissolved in 18 mL of dichloromethane (DCM). To the solution was added meta-67 chloroperoxybenzoic acid (m-CPBA) (77%, 1.50 g, 6.70 mmol) in 15 mL DCM and trifluoromethanesulfonic acid (TfOH) (98%, 1.2 mL, 13.56 mmol) at room temperature. The yellowish mixture turned into dark brown during the process. After stirring for one hour at ambient temperature, the solvent was decanted by rotary evaporation. 20 mL of diethyl ether (Et2O) was added into the round bottom flask and stirred for 10 min, during which a white solid precipitated. The white solid was filtered under vacuum and washed with Et2O three times (15 mL each time) to afford DPEI-OTf (1.78 g, 93% yield) as a white solid sample. Scheme 2.3 Synthesis of DPEI-OTf. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.49 (dd, J = 7.8, 1.3 Hz, 2H), 8.22 (dd, J = 8.1, 1.0 Hz, 2H), 7.86 (td, J = 7.6, 1.1 Hz, 2H), 7.72 (ddd, J = 8.5, 7.3, 1.3 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 141.8, 131.2, 130.8, 130.7, 127.1, 122.4, 121.7. 19F NMR (400 MHz, Dimethyl sulfoxide-d6) δ -77.7 (s, CF3). Fourier-transform infrared (FT-IR) spectroscopy [KBr, ?̃? = cm-1]: 1624.1 (w), 1582.1 (w), 1561.2 (w), 1457.5 (w), 1442.0 (m), 1422.5 (m), 1252.2 (s), 1177.7 (s), 1158.9 (s), 1027.5 (s), 1014.8 (s), 993.0 (m), 982.7 (w), 954.2 (w), 755.0 (m), 739.3 (s), 635.9 (s), 574.2 (m), 517.2 (m). HRMS (ESI): m/z [M-TfO]+ calcd for C12H8I+: 278.96652; found: 278.96738. The spectral data well aligns with the literature.118,119 68 Synthesis of dibenzo[b,d]iodol-5-ium chloride (DPEI-Cl) The anion exchange from triflate to chloride was carried out based on the procedures from literature (Scheme 2.4).120 Sodium chloride (NaCl) aqueous solution (60.0 mg, 1.03 mmol NaCl was dissolved in 10 mL of deionized water) was slowly added to a stirred aqueous solution of DPEI-OTf (325.5 mg, 0.76 mmol DPEI-OTf powder was dissolved in 15 mL deionized water). After vigorously stirring for 30 min, the pale white precipitate was filtered off and rinsed with deionized water (2 x 5 mL) followed by 5 mL of diethyl ether. The obtained white solid was collected (191.3 mg, 80% yield) and dried under high vacuum overnight. We have grown the crystals for this compound, though it has been published already.95 Scheme 2.4 Anion exchange from triflate into chloride for DPEI series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.55 (dd, J = 8.0, 1.0 Hz, 2H), 8.43 (dd, J = 8.0, 1.2 Hz, 2H), 7.81 (m, J = 7.5 Hz, 2H), 7.67 (m, J = 7.8 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 141.4, 130.7, 130.5, 130.4, 126.4, 124.1. FT-IR [KBr, ?̃? = cm-1]: 1634.7 (w), 1580.9 (m), 1561.8 (w), 1457.4 (w), 1441.8 (s), 1422.6 (s), 1408.1 (m), 1302.1 (m), 1162.3 (w), 1130.2 (w), 1052.8 (w), 1031.3 (m), 1016.1 (m), 994.4 (m), 944.4 (w), 740.4 (s), 647.5 (w), 609.5 (w), 470.5 (w). CH (%) = calc: C: 45.82, H: 2.56; found: C: 45.36, H: 2.31. 69 Synthesis of dibenzo[b,d]iodol-5-ium bromide (DPEI-Br) The anion exchange from triflate to bromide was initially performed according to the synthetic method of DPEI-Cl, but the formed precipitates was too small to be collected using vacuum filtration. One possible reason is that the DPEI-Br has a better solubility in water than DPEI-Cl. Therefore, the procedure was modified as follows (Scheme 2.5): 230.9 mg (0.54 mmol) of DPEI-OTf was dissolved in 15mL of methanol at room temperature. Excess (209.5 mg, 0.65 mmol) of tetra-n-butylammonium bromide (TBABr) solution (TBABr was dissolved in 10 mL of methanol was added to the stirred solution. White solid precipitated immediately. The mixture was stirred for 30 min before vacuum filtration. The collected white powder was washed with methanol (2 x 5 mL) and 5 mL of diethyl ether followed by vacuum drying overnight. The mass of the dried powder is 147.9 mg (76% yield) (Note: The corresponding bromide salt was changed from NaBr to TBABr since the medium was switched from aqueous to organic environment and NaBr has a relatively poor solubility in organic solvents). Scheme 2.5 Anion exchange from triflate into bromide for DPEI series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.51 (d, J = 8.2 Hz, 2H), 8.45 (d, J = 7.9 Hz, 2H), 7.83 (t, J = 7.5 Hz, 2H), 7.68 (t, J = 7.8 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 141.3, 130.8, 130.7, 130.6, 126.5, 123.6. 70 FT-IR [KBr, ?̃? = cm-1]: 1580.5 (m), 1457.9 (w), 1441.6 (m), 1421.7 (m), 1406.6 (w), 1302.4 (w), 1161.8 (w), 1130.1 (w), 1052.9 (w), 1031.9 (w), 1014.6 (w), 992.5 (w), 942.5 (w), 738.1 (s). CH (%) = calc: C: 40.15, H: 2.25; found: C: 40.01, H: 2.12. Synthesis of dibenzo[b,d]iodol-5-ium iodide (DPEI-I) The anion exchange from triflate to iodide was first carried out using the same method of triflate-to-bromide exchange, but the yield was too low after vacuum filtration. The DPEI-I is expected to have a better solubility in methanol than DPEI-Br. Consequently, the solvent was switched from methanol to acetonitrile which has a lower polarity (Scheme 2.6): 245.1 mg (0.57 mmol) of DPEI-OTf was dissolved in 15 mL of acetonitrile and excess (250.6 mg, 0.68 mmol) tetra-n-butylammonium iodide (TBAI) solution (TBAI was first dissolved in 10 mL of acetonitrile) was added portion-wise to the stirring solution at room temperature. Pale white precipitation formed immediately after the addition of TBAI. The sample was stirred for 30 min before filtration. The precipitate was washed by acetonitrile (2 x 5 mL) and 5 mL of diethyl ether and dried under vacuum, affording 144.9 mg of the target compound (62% yield). Scheme 2.6 Anion exchange from triflate into iodide for DPEI series. 71 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.45 (d, J = 8.2 Hz, 2H), 8.45 (d, J = 8.2 Hz, 2H), 7.84 (m, J = 7.7 Hz, 2H), 7.69 (m, J = 7.8, 1.2 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 141.2, 130.9, 130.8, 130.7, 126.6, 122.9. FT-IR [KBr, ?̃? = cm-1]: 1616.9 (w), 1580.0 (m), 1560.0 (w), 1454.5 (w), 1440.2 (m), 1419.8 (s), 1404.4 (w), 1304.8 (w), 1162.5 (w), 1127.9 (w), 1033.4 (w), 1012.4 (m), 987.7 (w), 741.1 (s). Preparation of diphenyliodonium trifluoromethanesulfonate (DPI-OTf) and diphenyliodonium trifluoromethanesulfonate (DPI-Cl) Both complexes were purchased from Sigma Aldrich and TCI and utilized without further purification. We have grown the crystals for both compounds, though they have been published already.100,121 For DPI-OTf: 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.24 (m, J = 8.1 Hz, 4H), 7.66 (tt, J = 7.5, 1.1 Hz, 2H), 7.53 (tt, J = 8.0, 1.6 Hz, 4H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 135.2, 132.1, 131.8, 116.7. 19F NMR (400 MHz, Dimethyl sulfoxide-d6) δ -77.7 (s, CF3). For DPI-Cl: 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.15 (m, J = 8.1 Hz, 4H), 7.58 (tt, J = 7.4, 1.2 Hz, 2H), 7.46 (tt, J = 7.7, 1.7 Hz, 4H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 134.9, 131.3, 131.2, 120.2. 72 CH (%) = calc: C: 45.53, H: 3.18; found: C: 45.48, H: 3.22. Synthesis of diphenyliodonium bromide (DPI-Br) 232.14 mg (0.73 mmol) of DPI-Cl complex was dissolved in 15 mL of deionized (DI) water at room temperature. 89.9 mg (0.87 mmol) of sodium bromide (NaBr) dissolved in 10 mL of DI water was added dropwise to the round bottom flask containing DPI-Cl solution. Clear solution turned cloudy immediately. After 30 min, the precipitate was filtered and flushed with methanol (2 x 5 mL) and 5 mL of diethyl ether. The collected white powder was dried under high vacuum overnight, affording 138.9 mg (53% yield) of desired product. We have grown the crystals for this compound, though they have been published already.121 Scheme 2.7 Anion exchange from chloride into bromide for DPI series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.20 (m, 4H), 7.62 (tt, J = 7.4, 1.1 Hz, 2H), 7.49 (tt, J = 7.9, 1.5 Hz, 4H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 135.0, 131.6, 131.5, 118.8. 73 Synthesis of diphenyliodonium iodide (DPI-I) The procedure of anion exchange from chloride into iodide is similar to that from chloride to bromide. 224.10 mg (0.71 mmol) of DPI-Cl was dissolved in 15 mL of DI water followed by the slow addition of sodium iodide solution (133.40 mg, 0.89 mmol of NaI in 10 mL of DI water) with stirring. After half-hour reaction, the precipitate was filtered, washed, and dried to afford DPI-I as a pale white solid (224.50 mg, 78%). We have grown the crystals for this compound, though they have been published already.121 Scheme 2.8 Anion exchange from chloride into iodide for DPI series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.23 (m, J = 8.2 Hz, 4H), 7.65 (tt, J = 7.4, 1.1 Hz, 2H), 7.51 (tt, J = 7.9, 1.5 Hz, 4H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 135.2, 131.9, 131.7, 117.5. Synthesis of dibenzo[b,d]bromol-5-ium trifluoromethanesulfonate (DPEBr-OTf) 74 The synthesis of DPEBr-OTf was carried out analogous to the reported paper by Matteo et. al.119 2-iodoanilines (1 equiv.), 2-bromophenylboronic acid (1.2 equiv.), tetrakis(triphenylphosphine)palladium(0) (5 mol%), and NaHCO3 (3 equiv.) were first added to a dry Schlenk flask, followed by 0.35 M dimethoxyethane (DME). The mixture was stirred at room temperature for 10 min and H2O was charged. Then the mixture was stirred at 120 °C for 2 hours. After being cooled down to room temperature, it was extracted with ethyl acetate (AcOEt), dried over sodium sulfate (Na2SO4), and filtered. Subsequently, the volatile components were removed from the filtrate, and the crude product was purified by chromatography, affording the desired product 2'-bromo-[1,1'-biphenyl]-2-amine (yield ~ 90%). The obtained 2'-bromo-[1,1'-biphenyl]-2-amine (2.89 g, 11.4 mmol) was dissolved in dry and degassed acetonitrile and cooled to 0 °C. Triflic acid (3.36 g, 22.4 mmol) and tert-Butyl nitrite tBuNO2 (2.3 g, 22.4 mmol) were then added at 0 °C and left to stir for 1 hour. The dark green solution was then heated for 2.5 hours at 65 °C. The reaction was cooled to room temperature before removing the volatiles under reduced pressure. To the oily residue was then added ethyl acetate generating a suspension. The solid was filtered via Buchner filtration and dried under reduced pressure to give the product as an olive green solid (1.05g, 2.75 mmol, 24% yield). Scheme 2.9 Synthesis of DPEBr-OTf. 75 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.60 (dd, J = 7.8, 1.6 Hz, 2H), 8.48 (dd, J = 8.6, 0.9 Hz, 2H), 7.96 (m, J = 7.5, 1.0 Hz, 2H), 7.85 (m, J = 8.0, 1.6 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 136.7, 135.4, 131.9, 131.3, 126.4, 125.6. HRMS (ESI): m/z [M-TfO]+ calcd for C12H8Br+: 230.98094; found: 230.98098. The spectral data well aligns with the literature.119 Synthesis of dibenzo[b,d]bromol-5-ium chloride (DPEBr-Cl) The synthesis reaction was shown in Figure 2.43. DPEBr-OTf (183.6 mg, 0.48 mmol) was dissolved in 15 mL of acetone in the ambient environment. 190.0 mg (0.68 mmol) of tetra-n-butylammonium chloride (TBACl) was added to the DPEBr-OTf solution. The resulting mixture was stirred for 30 min and filtered. The pale greenish precipitate was collected and dried under high vacuum. Yield is 89 % (115.0 mg, 0.43 mmol). The crystal structure has been reported but with water molecules entangled in the crystal packing, while there are no solvent molecules found in our crystal structure.122 Scheme 2.10 Anion exchange from triflate into chloride for DPEBr series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.74 (dd, J = 8.6, 1.0 Hz, 2H), 8.57 (dd, J = 7.8, 1.4 Hz, 2H), 7.92 (m, J = 7.8, 1.0 Hz, 2H), 7.82 (m, J = 7.9, 1.5 Hz, 2H). 76 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 137.3, 135.4, 131.6, 131.1, 126.1, 126.0. CH (%) = calc: C: 53.87, H: 3.01; found: C: 53.87, H: 3.05. Synthesis of dibenzo[b,d]bromol-5-ium bromide (DPEBr-Br) The anion exchange method from DPEBr-OTf to DPEBr-Br is the same as that from DPEBr-OTf to DPEBr-Cl. 153.2 mg (0.40 mmol) DPEBr-OTf and 184.8 mg (0.57 mmol) TBABr reacted in acetone to afford desired product (110.1 mg, 0.35 mmol, 88%) as a pale green powder. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.63 (dd, J = 8.5, 0.9 Hz, 2H), 8.59 (dd, J = 7.9, 1.5 Hz, 2H), 7.94 (m, J = 7.9, 1.0 Hz, 2H), 7.84 (m, J = 7.9, 1.6 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 137.0, 135.4, 131.7, 131.2, 126.2, 125.9. Synthesis of dibenzo[b,d]bromol-5-ium iodide (DPEBr-I) The anion exchange method from DPEBr-OTf to DPEBr-I is the same as that from DPEBr-OTf to DPEBr-Cl. 168.0 mg (0.44 mmol) DPEBr-OTf and 207.3 mg (0.56 mmol) TBAI were mixed in acetone and formed a pale green product (127.8 mg, 0.36 mmol, 81%). 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.60 (dd, J = 7.8, 1.5 Hz, 2H), 8.52 (dd, J = 8.6, 0.9 Hz, 2H), 7.95 (m, J = 7.3, 1.0 Hz, 2H), 7.85 (m, J = 8.0, 1.6 Hz, 2H). 77 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 136.7, 135.4, 131.9, 131.3, 126.4, 125.7. Synthesis of dibenzo[b,d]chlorol-5-ium chloride (DPECl-Cl) The synthetic procedure was adapted from the preparation method of DPEBr-OTf. Firstly, [1,10 -biphenyl]-2-amine, 2’-chloro- was made according to the reference.123 (see Scheme 2.11) 2-bromoaniline (1 equiv.), 2-chlorophenylboronic acid (1.2 equiv.), Pd(PPh3)4 (0.05 equiv.), and NaHCO3 (3 equiv.) in 10 mL DME were mixed under stirring at ambient temperature for 10 min. 10 mL of H2O was subsequently added, and the resulting mixture was degassed in a dry ice-acetone bath, sealed, and stirred at 120 °C for 2 h. After cooling down to room temperature, the mixture was extracted with Et2O, dried over MgSO4, and filtered. After removal of volatile components from the filtrate, the resulting crude product was purified by chromatography to provide [1,10 -biphenyl]-2-amine, 2’-chloro- (yield ~88%) as an off-white solid. The purified [1,10 -biphenyl]-2-amine, 2’-chloro- (2.66 g, 13.1 mmol) was dissolved in dry acetonitrile and cooled to 0 °C. hydrochloric acid (955.3 mmg, 2.24 mL, 26.2 mmol) and oxidant tBuNO2 (2.701 g, 3.45 mL, 26.2 mmol) were then added at 0 °C and left to stir for 1h at 0 °C. Subsequently, the resulting mixture was raised to 65 °C and heated for 2.5 hours. The reaction was then cooled to room temperature at which point large amounts of solid precipitated. 200 mL of diethyl ether was charged in the flask and kept for stirring for several minutes before filtering the solid under reduced pressure via Buchner filtration, giving 1.37 g of an off-white-colored solid in 46% yield. 78 Scheme 2.11 Synthesis of DPECl-Cl. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.71 (dd, J = 8.6, 1.0 Hz, 2H), 8.68 (dd, J = 7.7, 1.7 Hz, 2H), 8.01 (td, J = 7.5, 1.1 Hz, 2H), 7.95 (ddd, J = 7.9, 1.8, 1.3 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 140.2, 132.1, 132.0, 131.8, 125.6, 123.1. HRMS (ESI): m/z [M-TfO]+ calcd for C12H8Cl+: 187.03145; found: 187.03144. Synthesis of dibenzo[b,d]chlorol-5-ium trifluoromethanesulfonate (DPECl-OTf) The method was adapted from the work done by Yasushi.122 1.15 equivalent of AgOTf (1.15 equiv.) was added to 1 equivalent of DPECl-Cl in MeOH (0.05 M) and stirred for 30 minutes at room temperature. The resulting mixture was filtered and washed with MeOH. The obtained filtrate was then evaporated and dried to give DPEI-OTf (yield ~85%). 79 Scheme 2.12 Anion exchange from chloride into triflate for DPECl series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.68 (dd, J = 7.7, 1.7 Hz, 2H), 8.66 (dd, J = 8.6, 1.0 Hz, 2H), 8.01 (td, J = 7.5, 1.1 Hz, 2H), 7.95 (ddd, J = 7.9, 1.7, 1.3 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 140.1, 132.1, 132.0, 131.8, 125.6, 123.0. Synthesis of dibenzo[b,d]chlorol-5-ium bromide (DPECl-Br) 309.6 mg (0.92 mmol) of DPECl-OTf in 20mL of acetone was charged into a round bottom flask, followed by the addition of 406.9 mg (1.26 mmol) of TBABr. The resulting mixture was stirred at room temperature for 30 minutes and a pale orange powder formed during the process. The precipitate was then filtered, washed with 5 mL of acetone and dried under vacuum to give a pale orange powder (137.9 mg, 0.52 mmol, 56%). Scheme 2.13 Anion exchange from triflate into bromide for DPI series. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.71 (dd, J = 8.6, 1.1 Hz, 2H), 8.68 (dd, J = 7.7, 1.7 Hz, 2H), 8.01 (td, J = 7.5, 1.1 Hz, 2H), 7.95 (ddd, J = 7.9, 1.7, 1.3 Hz, 2H). 80 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 140.2, 132.1, 132.0, 131.8, 125.6, 123.1. Synthesis of dibenzo[b,d]chlorol-5-ium iodide (DPECl-I) The anion exchange of DPECl system from triflate to iodide is the same as that from triflate to bromide. DPECl-OTf was mixed with TBAI in acetone solution to generate DPECl-I product. A pale purple powder was produced at 41% yield eventually. 1H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 8.68 (dd, J = 7.6, 1.4 Hz, 2H), 8.67 (dd, J = 8.6, 1.0 Hz, 2H), 8.02 (td, J = 7.5, 1.0 Hz, 2H), 7.95 (m, J = 8.7, 1.3 Hz, 2H). 13C NMR (400 MHz, Dimethyl sulfoxide-d6) δ 140.1, 132.1, 132.1, 131.8, 125.6, 123.0. Growth of crystal: DPEI-X and DPI-X series were crystallized by slow evaporation. About 2.0 mg of each sample was fully dissolved in ~0.5 mL of methanol (or methanol/acetonitrile mixture) in a small vial. The small vial was sealed by parafilm with only one small hole to ventilate. After 2-3 days, crystals that are suitable for single crystal X-ray diffraction were formed. However, DPEBr-X series have lower solubility in methanol and water solvents than DPEI-X and DPI-X. The mixture of dimethylacetamide and acetonitrile was added into 5.0 mg of each powder. The resultant mixture was heated to about 60 ~ 80 °C till the solids were completely dissoluted. The clear solution was then slowly cooled down to ambient temperature. The desired crystals were formed after 2 − 3 hours. 81 2.5.2 XAS Experiment Setup XAS sample preparation All samples were grinded into fine powders and dusted onto a chlorine-free Kapton tape across the window of a solid sample holder. Another layer of Kapton tape was then applied onto the sample to avoid contamination. XAS data collection Chlorine K-edge XAS data was collected at beamline 4-3 at SSRL. The sample was analyzed in a helium environment at ambient temperature. The beam is collimated and unfocused to allow for high energy-resolution (~1×10-4 ∆E/E) measurements on homogenous samples. It is equipped with a 4-element solid-state silicon drift detector in addition to ionization chambers and PIPS/Lytle detectors. The beam was detuned by 20% to attain harmonic rejection. KCl calibration scans were performed before and after each sample. XAS data analysis Athena was utilized for calibration, spectra average, background subtraction and normalization.124 The obtained KCl spectra were used as a reference for Cl K-edge spectra.16 BlueprintXAS version 4.1.4 was applied for peak fitting and quantitative analysis. The fits were run in AUTO mode which uses a Monte Carlo methodology to choose the starting point of each fit and minimize user bias during data analysis.108 2.5.3 Computational Methods Quantum-mechanical calculations were run using the Gaussian 16 (G16)125 and ORCA 5.0.2126 computational package using WestGrid computing facility (Cedar or Graham). DFT part M06-2X is a decent functional which has been confirmed to have excellent performance in the calculations of intermolecular interactions.127,128 Therefore, all geometry optimizations were performed in G16 using the restricted M06-2X functional with an ultrafine integration grid. Correlation-consistent triple-zeta basis set with diffuse function aug-cc-pVTZ was applied to all atoms except bromine and iodine, as it is more accurate than commonly used 6-311G basis set and often recommended 82 for anion and weak interaction calculations.19,129 The aug-cc-pVTZ-PP basis set was applied on bromine and iodine, since effective core potential are usually used to account for relativistic effects in heavy atoms.130,131 All geometries were optimized to a minimum and frequency calculations were performed at the same level of theory to verify the absence of imaginary frequencies. TD-DFT part The optimized structures from DFT were re-optimized in ORCA 5.0.2 before the implementation of TD-DFT calculations. Based on our previously reported work,16 B3LYP and ZORA-def2-TZVP (with relativistic corrections) were used for all atoms except Br and I. OLD-ZORA-TZVP basis sets were used for the Br and I atoms. Cl K-edge XAS TD-DFT simulations were carried out using the same functional and basis sets as in the optimization step. 83 Chapter 3: Probing the Nature of Chalcogen Bonding in Ionic Systems ChBs have not been explored to the same extent as XBs and thus questions remain about the characteristics of such chemical bonds and how they can be manipulated to enhance their electronic properties. Given the lack of available spectroscopic studies on ChBs, we have carried out a systematic study of a series of well-defined ChB systems to explore the nature of such bonds and provide a foundation for future exploitation on these underexplored weak interactions. To the best of our knowledge, these studies have represented the first spectroscopic evaluation of electronic properties related to ChBs. Inspired by chapter 2 where ionic pairs have induced strong XB interactions, a series of ChB complexes with ionic core structures were selected to probe the nature of strong ChBs. In collaboration with Dr. Paul Beer Group at University of Oxford, we have investigated a group of ChB-involved compounds with spectroscopic and computational approaches. A further comparison with HB and XB has also been done to elucidate the differences among common weak interactions. Five bis-triazole-pyridinium-containing salts were chosen as the model compounds. As shown in Figure 3.1, the overall skeleton of each compound is the same. The hydrogen atom (or iodine, or tellurium) is directly attached to a triazole group that concurrently binds to a pyridinium and a 2,3,5,6-tetrafluoro-4-methylbenzoate substituents. The cationic backbone, in combination with various electron-withdrawing groups, is expected to deplete electron density from the hydrogen/halogen/chalcogen atoms; thus inducing a relatively strong interaction. The additional substituents on tellurium are different among three ChB systems: Te atoms in 1_ChB_Cl are methylated; Te in 2_ChB_Cl is attached to a phenyl group, which is often electron withdrawing 84 by inductive effect, though sometimes electron-donating through resonance effect; Te of 3_ChB_Cl binds to a 3,5-bis-trifluorophenyl moiety that makes the cationic molecule even more electron-deficient. The comparison of binding constants in the mixture of CD3CN (deuterated acetonitrile) and DMSO were provided by our collaborators: 1_XB_Cl > 3_ChB_Cl > 1_ChB_Cl > 2_ChB_Cl > 1_HB_Cl. Figure 3.1 Structures of the bis-triazole-pyridinium-containing model compounds. 3.1 Comparison of Electronic Structures among HB, XB, and ChB Cl K-edge XAS has also been applied to study the electronic structures among different weak interactions. The comparison of XAS results is shown in Figure 3.2. Each sample exhibit a noticeable pre-edge feature in the range of 2816.0 ~ 2818.0 eV, indicating the partially covalent characteristic of these weak interactions.16,19 As mentioned in section 2.3.2, fitting the pre-edge 85 and edge jump using BlueprintXAS allows for quantification of the degree of charge transfer in those species. The fitting results are tabulated in Table 3.1, which clearly demonstrate the trend of covalent contributions among the three SBIs: XB > ChB > HB. Herein, the degree of charge transfer follows the trend of the binding strengths. Figure 3.2 XAS comparison of 1_HB_Cl, 1_XB_Cl and 1_ChB_Cl complexes after normalization and background subtraction. Table 3.1 Spectroscopically resolved pre-edge intensities and the corresponding % charge donation from chloride donor. entry pre-edge energy (eV) normalized pre-edge intensity %Cl3p total charge donation 1_HB_Cl 2816.62 ± 0.01 0.2 ± 0.0 1.6 ± 0.7 1_XB_Cl 2817.70 ± 0.01 1.4 ± 0.0 9.9 ± 0.7 1_ChB_Cl 2817.74 ± 0.10 1.0 ± 0.1 6.8 ± 0.8 86 TD-DFT simulations of XAS data were also carried out to further explore the different nature of charge donations in XB and ChB (The details of the calculation are described in section 3.4). Since the degree of charge transfer in HB is very low, the orbital analysis was not studied in this part. The TD-DFT results well align with the XAS data, in which the pre-edge of 1_XB_Cl is sharper and more intense than that of 1_ChB_Cl. In fact, there are two pre-edge features in 1_ChB_Cl, the second of which may be buried under the edge jump in XAS spectrum. The reason why the curve of 1_ChB_Cl is broader is that the transitions in 1_ChB_Cl adduct is more complicated than 1_XB_Cl, as shown in Figure 3.4. In 1_XB_Cl system, there are two intense pre-edge transitions representing two σ interactions between Cl- (i.e., Cl 3px and Cl 3py orbitals if z axis is pointing into the paper) and the cationic moiety. The chloride donor in 1_ChB_Cl also interacts with Te through σ-manner ChB. However, it also communicates with π electrons in adjacent triazole or pyridinium rings, which has complicated the pre-edge transitions in 1_ChB_Cl adduct. In Figure 3.5, crystal structures of the two compounds were provided by Dr. Paul Beer group. The circled area in 1_XB_Cl is not on the same plane while the central part of 1_ChB_Cl is co-planar. It may account for the existence of π delocalization in 1_ChB_Cl system. Figure 3.3 TD-DFT simulated Cl K-edge XAS spectra for 1_XB_Cl and 1_ChB_Cl adducts. A constant linear shift was applied to the calculated energies to match experimental energies.113 87 Figure 3.4 TD-DFT simulated Cl K-edge XAS spectra for 1_XB_Cl and 1_ChB_Cl adducts. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). Figure 3.5 Crystal structures of 1_XB_Cl and 1_ChB_Cl. The numbers labelled on the picture represent the lengths of XB or ChB (unit is Å). The side view of each molecule is attached below (C: grey; H: white; N: light blue; O: red; F: yellow; Cl: green; Te: orange; I: purple). 3.2 Comparison of Electronic Structures among Different ChB Systems Methyl, phenyl, and 3,5-bis-trifluorophenyl substituents have been adapted to modulate the binding strength of ChB. In Figure 3.6, both 2_ChB_Cl and 3_ChB_Cl adducts exhibit two distinct 88 pre-edge features in Cl K-edge XAS spectra, which are different from those HB and XB systems. From the experiments carried out by Dr. Paul Beer group, the binding strength of ChB increases from 2_ChB_Cl to 1_ChB_Cl and 3_ChB_Cl. The pre-edge intensities do not follow the trend of the binding strength (Table 3.2). The Cl3p total charge donations in 2_ChB_Cl and 3_ChB_Cl are even higher than some conventional XBs. It contradicts with the experimental results in which the binding constant of 1_XB_Cl is stronger than all the ChBs, which again confirms that it is inappropriate to directly correlate the degree of charge donation with binding strength. It’s worth noting that the XAS analysis was carried out in solid state, but the binding constant were obtained in solution state. The effects related to the solvent (especially in the entropy part) are not taken into consideration here. Figure 3.6 XAS comparison of 1_ChB_Cl, 2_ChB_Cl and 3_ChB_Cl complexes after normalization and background subtraction. 89 Table 3.2 Spectroscopically resolved pre-edge intensities and the corresponding % charge donation from chloride donor. entry pre-edge energy (eV) normalized pre-edge intensity %Cl3p total charge donation 1_ChB_Cl 2817.74 ± 0.10 1.0 ± 0.1 6.8 ± 0.8 2_ChB_Cl 2817.84 ± 0.01 2819.12 ± 0.04 1.9 ± 0.0 0.8 ± 0.1 18.7 ± 1.1 3_ChB_Cl 2817.61 ± 0.04 2819.15 ± 0.09 1.0 ± 0.1 1.7 ± 0.1 19.0 ± 1.7 TD-DFT simulations have disclosed more details of the three ChB systems. Like 1_ChB_Cl in Figure 3.4, 2_ChB_Cl and 3_ChB_Cl are predicted to have two obviously different pre-edge peaks. The first two transitions in 2_ChB_Cl represent the σ-type donation from Cl 3px and 3py to Te which also resonates with the neighboring phenyl group. The transitions underneath the second pre-edge peak are intriguing. The chloride donor interacts with the left Te via σ-interaction and communicates with the right Te through π-type ChB. 3_ChB_Cl is more complicated than the previous two series, in which the transitions are more similar to those in 1_ChB_Cl adduct. The entanglement of σ and π characters were not observed in 3_ChB_Cl. It is worth mentioning that the ChB adducts in this chapter are basically similar to the hypervalent halogen (III) series in chapter 2. The two electron-deficient areas on chalcogen atom [or halogen (III) atom] at the extension of two covalent bonds have complicated the interactions to a large extent. To be more specific, both of the Te and halogen (III) are attached to at least one freely rotating phenyl ring. The involvement of π electrons has produced the second pre-edge feature which is about 1~1.5 eV apart from the first one. 90 Figure 3.7 TD-DFT simulated Cl K-edge XAS spectra for 2_ChB_Cl adduct. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). Figure 3.8 TD-DFT simulated Cl K-edge XAS spectra for 3_ChB_Cl adduct. The inserted pictures are the EDDMs for the corresponding transitions (isovalue is set as 0.0008). 91 3.3 Conclusion In this chapter, Cl K-edge XAS was used to investigate the nature of three different weak interactions, i.e., HB, XB, ChB. It is found that 1_XB_Cl has higher covalent contribution than 1_ChB_Cl and 1_HB_Cl. Different substituents attached to Te atom can significantly affect the ChB strength and the degree of charge transfer thereof. It again confirms that it is inappropriate to directly correlate the degree of charge donation with binding strength. 2_ChB_Cl and 3_ChB_Cl exhibit a substantial degree of covalency within ChB, which are even higher than conventional XBs. It is the first experimental evidence for charge donation in ChB, which provides critical insights into further understandings of it. Furthermore, the involvement of both σ and π characters of ChB was observed in 2_ChB_Cl system. This may have important implications in ChB-based molecular electronics. 3.4 Methods Sample preparation The five model compounds were provided by Beer group without further purification. XAS sample preparation All samples were grinded into fine powders and dusted onto a chlorine-free Kapton tape across the window of a solid sample holder. Another layer of Kapton tape was then applied onto the sample to avoid contamination. XAS data collection Chlorine K-edge XAS data was collected at beamline 4-3 at the SSRL. The sample was analyzed at ambient temperature and a helium environment. The beam is collimated and unfocused to allow for high energy-resolution (~1×10-4 ∆E/E) measurements on homogenous samples. It is equipped with a 4-element solid-state silicon drift detector in addition to ionization chambers and PIPS/Lytle detectors. The beam was detuned by 20% to attain harmonic rejection. KCl calibration scans were performed before and after each sample. 92 XAS data analysis Athena was utilized for calibration, spectra average, background subtraction and normalization.124 The obtained KCl spectra were used as a reference for Cl K-edge spectra.16 BlueprintXAS version 4.1.4 was applied for peak fitting and quantitative analysis. The fits were run in AUTO mode which uses a Monte Carlo methodology to choose the starting point of each fit and minimize user bias during data analysis.108 Computational Details Quantum-mechanical calculations were run using ORCA 5.0.2126 computational package using WestGrid computing facility (Cedar). The compounds in this system are similar to those in our previously published paper, the selection of functional and basis set has been considered effective.16 DFT part: All geometry optimizations were performed using the restricted B3LYP functional with def2-SVP basis set and a defgrid3 integration grid; All geometries were optimized to a minimum and frequency calculations were performed at the same level of theory to verify the absence of imaginary frequencies. TD-DFT part: Cl K-edge XAS spectra were simulated using TD-DFT calculations based on the optimized structures from DFT calculations. B3LYP and ZORA-def2-TZVP (with relativistic corrections) were used for all atoms except I and Te. OLD-ZORA-TZVP basis sets were used for the I and Te atoms. 93 Chapter 4: Exploring the Function of XB in Halogen-Containing Chemical Reactions The resurgence of interest in XBs as valuable aids in materials, synthesis and catalysis has brought greater attention to the fundamental nature of such chemical bonds and how they can be utilized in different ways. In chapter 2, we have mainly focused on the nature of XB, especially in solid states. Herein, a more appliable scenario will be presented in which how the chemical reaction in solution is controlled by XB is to be discussed. 4.1 Background Carbon-heteroatom (C−X) bond cleavage is a process of vital importance in many chemical reactions. In the past several years, the Huber group has demonstrated that the di-cationic imidazolium,132 pyridinium,133 and triazolium-based134 electron acceptors may serve as stoichiometric activators in reactions involving a C−X bond cleavage. In addition, neutral halogen-bond acceptors were also used as organo-catalysts in these benchmark reactions.135 The most straightforward descriptor of interaction strength is the binding constant K, or alternatively, its reciprocal, the dissociation constant Kd. Sebastian M. Walter et al. have successfully introduced NMR titration and isothermal titration calorimetry to characterize the bond strength of XB formed in the aforementioned organocatalytic process.136,137 However, according to all these determinations, it is still unclear of the real mechanistic pathway in the reaction, or more precisely, whether the halogenated activators (electron acceptors) bind to the neutral substrate, or to a halide anion that is liberated in equilibrium from the substrate. Therefore, more convincing evidence for the C−X bond cleavage activation by halogen bonding is still lacking. 94 In chapter 2, we have directly evidenced an unexpectedly large degree of charge transfer in certain XB interactions. It was achieved by XAS which provides quantitative information of charge depletion in the electron donor. In fact, the charge transfer in the electron acceptor can also be qualitatively examined by acceptor-oriented XAS. Herein, we employed XAS as a tool to probe the degree of charge transfer between substrate and activator or product and activator in a benchmark reaction as shown in Scheme 4.1. DFT and TD-DFT calculations were also carried out to provide computational evidence regarding the nature of XB. This work compares the dominance of different activating mechanisms during the process. In the long term, we seek to quantify charge transfer in different XB systems as a means of bond nature identification. Scheme 4.1 Top: Reaction of benzhydryl bromide with various activating reagents in wet CD3CN; Bottom: several examples of tested activators. BArF stands for tetrakis[3,5-bis(trifluoromethyl)phenyl]borate counterion, and pBArF stands for Tetrakis(pentafluorophenyl)borate counterion. 95 4.2 Investigations on Mechanistic Pathways The tested reaction is shown in Scheme 4.1.132 Monitoring the yields within a specific period (typically 96 h) confirms that the addition of activators can effectively speed up the benchmark reaction. Participation of XB is considered as a critical factor of inducing such a difference. Based on the reaction equation, we propose two hypotheses (in Scheme 4.2) to explain how the activating agents might enhance the reactivity: (1) the kinetic hypothesis -- benzhydryl bromide could coordinate the activating agent, donating electron density into its amplified sigma hole, which would either simply increase its electrophilicity, thereby activating it towards nucleophilic attack by SN2 reaction or, in the extreme case, reduce the kinetic barrier of heterolytic cleavage, activating it towards nucleophilic attack by SN1 reaction; or (2) the thermodynamic hypothesis -- the bromide leaving group could coordinate the activating agent in a thermodynamically favorable manner, shifting the equilibrium of the substitution reaction towards the products. Scheme 4.2 Schemes for the two hypotheses. 4.2.1 Probing the Reaction Mechanism using XAS Techniques If the activator-substrate complexes are examined using Br K-edge XAS, two different cases are expected: (1) If the activator is a spectator species which does not interact with substrate at all, the spectrum of the activator-substrate complex would be the same as that of the substrate itself. In 96 the molecular orbital diagram of the substrate (benzhydryl bromide) (see Figure 4.1 left), the transition of interest for excited 1s core electrons can be into both empty σ*C-Br and Br5p orbitals. It indicates that there is supposed to be an intense pre-edge feature before the edge jump in the spectrum of benzhydryl bromide. (2) If activator binds to benzhydryl bromide via XB, the C-Br bond is expected to be weakened, lowering the energy level of σ*R-Br orbital. In other words, if a prominent XB is formed between activator and substrate, the pre-edge feature of the Br K-edge XAS spectrum of the complex would shift to a lower energy level as described in Figure 4.1 (right). If this is observed in the XAS result, the hypothesis 1 is validated. Figure 4.1 The molecular orbital diagram of the covalently-bound bromine in substrate before and after binding with activators. The transitions of interest in Br K-edge XAS are shown in green. To explore the relationship between the activator and the product Br- (i.e., leaving group in this reaction), we have employed donor-oriented Br K-edge XAS. In our case, if the dissociated bromide ions are free in the solution, one would expect to see a simple K-edge XANES spectrum with a sharp edge jump, since the filled 4p orbitals in Br- prevents the electric-dipole allowed transition Br4p ← Br1s (see Figure 4.2 left). However, if the activator traps the bromide through XB, a fully occupied 4p orbital in Br- could generate a new set of bonding and antibonding orbitals σC-Brσ*C-BrBr1sBr5pSynchrotronRadiationBefore σC-Brσ*C-BrBr1sBr5pSynchrotronRadiationAfter97 with the activator-derived σ*X-R orbital, shown in Figure 4.2 (right). In other words, the electron delocalization through “XB channel” would lead to a newly allowed transition from 1s to σ*XB (antibonding orbital generated by Br4p in Br- and σ*X-R in the activator) for excited core electrons. Therefore, a pre-edge feature in the spectrum would rise, representing the excitation from 1s to the lowest unoccupied molecular orbital (LUMO) with partial bromine 4p character. The appearance of pre-edge features in the spectra of activator-product complexes will support the second hypothesis. Figure 4.2 The molecular orbital diagram of the product bromide before and after binding with activators via XB. The transitions of interest in Br K-edge XAS are shown in orange. For example, the iodinated activator 1 (A1) has been confirmed to have excellent performance in activating the reaction while the chlorinated one A2 is almost inert. In the XAS spectra (see Figure 4.3a), the curve of substrate-A2 complex shows nearly no difference when compared to the substrate itself. In contrast, a slightly shift of the pre-edge energy and an increase of pre-edge intensity were observed in the spectrum of substrate-A1 mixture. Such comparison has validated hypothesis 1 to some extent. Upon the addition of an effective activator, the C-Br bond will be 98 weakened via interactions between the activator and the substrate. Further comparison of different activators has drawn the same conclusion, which were not all given in this chapter. However, strong correlation between the pre-edge shift and the relative activating performance is inconclusive since the pre-edge shifts in all the tested systems are not significant. As shown in Figure 4.3b, the addition of A2 has almost no impact on the electronic environment of bromide ions, while introducing A1 distinctly leads to the appearance of a new feature preceding the edge jump. It indicates that the second hypothesis is reasonable in such system where the leaving group will be trapped by the activators through XBs. In summary, this organocatalytic process is synergistically controlled by kinetic and thermodynamic factors (i.e., both hypothesis 1 and 2), but the thermodynamic influence (i.e., the bromide leaving group coordinates with the activator in a thermodynamically favorable way) is more dominant. Figure 4.3 Br K-edge XAS spectra of substrate (a) and TBABr (b) upon addition of 1 equivalent of different activators, respectively. The black line stands for the substrate (a) or TBABr (b) itself. The red line represents the sample with the addition of A1. The blue line shows the sample with the addition of A2. 99 4.2.2 Probing the Reaction Mechanism using DFT Calculations To further explore a reasonable reaction pathway of the process, we performed a set of mechanistic DFT and thermochemistry calculations (The details of calculation are described in section 4.5). Since the currently used substrate benzhydryl bromide invariably constitutes a good SN1 substrate, it seems to go through SN1 reactions in the process. We also made every effort but failed to find the transition states of SN2 pathway in DFT calculations, which is in accord with chemical intuition that it should be SN1. Therefore, we proposed three different SN1 reaction pathways, shown in Scheme 4.3. The first pathway SN1-null represents the contrast course without the participation of any activator. In the second type SN1-a, the halogenated activator binds to the substrate from the very beginning which facilitates the dissociation of bromine from the reactant. In SN1-b, the activator does not interact with substrate due to a negligible XB between, while it traps the self-dissociated bromide ion via a much stronger XB at the end. To determine the soundest pathway, DFT calculations were carried out on the three hypothesized paths, respectively. Scheme 4.3 Three proposed SN1 reaction pathways, named SN1-null, SN1-a, and SN1-b. 100 From the energy profile shown in Figure 4.4, the kinetic barrier in the first step is as high as 18.6 kcal/mol when there is no activator present. If the activator participates in the reaction by forming XB with substrate (in SN1-a), the kinetic barrier is largely decreased to 7.7 kcal/mol even though it sacrifices 5.2 kcal/mol to form the initial binding complex. In SN1-b process, the energy of the transition state keeps the same while the intermediate lowers its energy for 7.1 kcal/mol which favors the first step in a thermodynamic manner. In the second step of the reaction, the activator traps the bromide leaving group which lowers the kinetic barrier from 15.9 kcal/mol to 13.2 kcal/mol. Overall, SN1-a is the most favourable pathway among the three pathways. Structures of the involved reactant, transition state, intermediate and product are shown in Fig. 4.4b. The bromine atom is initially bound to the activator in a bidentate way via XB interaction. Once the bromide ion is completely trapped by the activator, the substrate-derived carbocation would be attacked by acetonitrile molecule to generate final product. XBs have played two significant roles throughout the reaction: it weakens the C-Br bond of the substrate at the first stage and reduces interference from free bromide ions when acetonitrile attacks carbocation. In contrast to our spectroscopic results, we do observe the XB formation between both activator/substrate and activator/product. In conclusion, the additive halogenated activators bind to the substrate and the leaving group via XBs, which facilitate the reaction in a thermodynamically and kinetically favorable manner. 101 Figure 4.4 The energy profile of three proposed pathways according to DFT calculation (a); Structures of reactant, transition state, intermediate and product in SN1-a pathway (b) (C: grey; H: white; N: blue; Br: dark red; I: purple). 4.3 The Effects of Different Activators 4.3.1 Comparing Different Activators using XAS and TD-DFT Methods From the experimental results, we know that: (1) the catalytic performance of di-iodinated activators in the benchmark reaction is much better than that of the mono-iodinated ones; (2) the 102 iodinated activators are superior to the chlorinated ones; (3) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BArF) counterion is less coordinative than tetrakis(pentafluorophenyl)borate (pBArF); (4) cationic activators are more active than the neutral ones. In all cases, the intensities of the pre-edge features in activator-bromide complexes well correlate with the experimental performance of each activator (Note: in the XAS experiments, the source of bromide is TBABr). As illustrated in Figure 4.5, those with better activating performance exhibit a more distinct pre-edge feature, suggesting a larger extent of covalency in the formed XB. Figure 4.5 XAS spectra of different activator-bromide complexes. The bromide source is TBABr. 103 Since the pre-edge feature in Br K-edge XAS is not distinct, it is difficult to quantitively analyze the spectra. Given the relative insensitivity of Br K-edge XAS, donor-oriented Cl K-edge XAS was then employed to verify the strong XBs formed between activators and halides. By the same token, it is expected to observe a simple K-edge XANES spectra with a sharp edge jump with regards to free chlorides in the solution system. If activator binds to Cl- via XB, a newly allowed unoccupied orbital σ*XB would form due to the interaction of the occupied 3p orbital in Cl- and the σ*X-R orbital from activator, shown in Fig. 4.6a. Tetra-n-butylammonium chloride (TBACl) was used as the source of chloride. Upon addition of 1 equivalent of the activator, the electronic structure of Cl- has a dramatic change. Figure 4.6 provides an exemplary comparison between A3 and A7. As stated, the intensities of the σ*C-I←Cl- ← Cl1s pre-edge transitions correlate with the degree of charge transfer from the chloride to the acceptor. The trends of calculated pre-edge intensities and the corresponding XB charge donation (in Table 4.1) are in agreement with those catalytic performances observed in experiments. (Note: the kinetic performance is based on the reference137 and some unpublished data from our collaborators.) Figure 4.6 (a) The molecular orbital diagram of the chloride ion involved in an XB with activators. The transitions of interest in Cl K-edge XAS are shown in green and orange, respectively; (b) Cl K-edge XAS spectra of TBACl upon addition of 1 equivalent of different activators, respectively. 104 Table 4.1 Experimentally obtained pre-edge intensities activator binding sites X…Cl- X…Br- pre-edge energy (eV) normalized pre-edge intensitya total donation (% Cl3p)b kinetic performancec A1 2 2821.6(3) 1.0(1) 7.2 2 A2 2 - ~0.0 - 4 A3 1 2821.4(1) 0.5(9) 3.6 3 A7 2 2821.5(4) 1.3(1) 9.0 1 A1 2 13472.5(0) 1.7(9) - 2 A2 2 - ~0.0 - 4 A3 1 13472.3(0) 1.1(9) - 3 A7 2 13472.4(0) 1.8(7) - 1 a. Calculated errors (parentheses) are obtained from statistical distribution of fit results for 150 fits for each data set. b. Total donation is calculated based on a CuCl42- reference; the reference system has not been established for Br K-edge yet, so the total donation is not applicable for data from Br K-edge XAS. c. The performance ranking is based on the kinetic data collected from experiment; 1 to 4 represents activating performance from best to worst. TD-DFT simulations of the XAS data were conducted to further study the covalent nature of XB in the reaction. In Figure 4.7, TD-DFT calculations of the Cl and Br K-edge XAS data reproduce the pre-edge feature assigned to the σ*XB ← X1s transition in each case. The inserted figures are the primary σ*(R-X ← X-) Kohn-Sham acceptor orbitals for A1 and A3 (Note: here, the σ*(R-X ← X-) orbital stands for the antibonding orbital generated from halide and its bonding partner). The calculated pre-edge intensities and corresponding XB charge donation are in good agreement with those obtained from the Cl K-edge XAS data. The mono-iodinated activator shows a lower-energy pre-edge feature when compared to the di-iodinated one. This small energy difference is related to decreased electron density on the chloride, which leads to stabilization of the Cl1s donor orbital.16 Similar trends can also be observed in bromide system; the TD-DFT simulations of bromide systems are also in reasonable agreement with the experimental and spectroscopic data. 105 Figure 4.7 TDDFT simulated Cl K-edge (a) and Br K-edge (b) XAS spectra for A1-X and A3-X. A constant linear shift was applied to the calculated energies to better match experimental K-edge energies.113 The inset figures are the primary σ* R-X ← X- Kohn-Sham acceptor orbitals for A1 and A3. Surface volume for each orbital is plotted for ± 0.03 e/Å3. 106 4.3.2 Comparing Different Activators by DFT Calculations DFT calculations were also applied to study the binding modes among different activator-substrate or activator-product combinations. Bidentate activator A1 is much more favorable in catalyzing the benchmark reaction than the monodentate one A3, which is corresponding to the spectroscopic and experimental outcomes.137 The Gibbs free energy change upon the formation of activator/substrate or activator/product complexes in Figure 4.8 clearly demonstrates that stronger XBs are generated between activator and product rather than substrate. Though the formation of XB in activator/substrate is an endergonic process, it’s a necessary sacrifice for a more favorable transition state and product. Compared with the bidentate XB module, mono-halogenated activators are expected to generate more binding modes with the substrate. Several A3’ variants have been investigated using DFT calculations. In Figure 4.9, A3’ (chlorinated) and A3’ (brominated) weakly interact with the substrate with a long interaction length (> 3.5 Å); while the iodinated activator shows a typical XB interaction with the substrate. The bromine of benzhydryl bromide is 3.51 Å away from the iodine and located at the extension of C-I bond. This also explains why iodinated molecules have better catalytic performance than those brominated or chlorinated ones. 107 Figure 4.8 Comparison between mono-iodinated and di-iodinated activators. To lower down the computational expenses, A3’ was used as a substitute of A3 in which the octyl group was replaced by a methyl group. ∆G0 represents the Gibbs free energy change after the formation of XBs under the standard conditions (C: grey; H: white; N: blue; Br: dark red; I: purple). Figure 4.9 Comparison among different A3’ variants (C: grey; H: white; N: blue; Cl: green; Br: dark red; I: purple). 108 4.4 Conclusion In this chapter, investigations on different XB systems (substrate/activator and product/activator) were carried out to confirm a more dominant way of activating a benchmark reaction. Cl and Br K-edge XAS were used to reveal the charge transfer among XB complexes. Quantitative fitting of the pre-edge features provided a direct measure of the degree of covalency in the XB interactions. The trend of the pre-edge change is in reasonable agreement with the catalytic performance observed in experiment. TD-DFT simulations were utilized to further rationalize the obtained spectroscopic data. It has confirmed the existence of σ-type characteristics in the involved XB interactions. Systematic DFT calculations were implemented to find the most likely mechanistic pathway for the reaction; it also validated some key factors (more polarizable atoms, more halogenated sites, favorable counterions) that would dramatically influence the strength of XB. Most importantly, this work perfectly connected experimental, spectroscopic, and computational results; it has provided a systematic method of predicting experimental outcomes in XB-activated reactions and is expected to guide a better experimental design (e.g., the XB pairs with higher degree of charge transfer are expected to show better catalytic performances). 4.5 Methods Synthetic methods The halogenated activators were provided by Huber group. They were prepared and characterized as previously described by Huber group.138–140 Acetonitrile (CH3CN, anhydrous, 99.8%) was purchased from Fisher Chemical and used as received. Benzhydryl bromide, TBABr and TBACl were purchased from Sigma Aldrich without further purification. XAS sample preparation All samples were fully dissolved in acetonitrile and then injected into the XAS-specific liquid sample holders. Activator-substrate complexes were made by mixing the 109 halogenated activator and benzhydryl bromide of 1:1 ratio. Activator-product complexes were the mixture of TBABr (or TBACl) and 1 equivalent of the activator. XAS data collection Chlorine K-edge XAS data was collected at beamline 4-3 at the SSRL. The sample was analyzed in a helium environment at ambient temperature. The beam is collimated and unfocused to allow for high energy-resolution (~1×10-4 ∆E/E) measurements on homogenous samples. It is equipped with a 4-element solid-state silicon drift detector in addition to ionization chambers and PIPS/Lytle detectors. The beam was detuned by 20% to attain harmonic rejection. KCl calibration scans were performed before and after each sample. Bromine K-edge XAS data was collected on beamline 7-3 at SSRL under ring conditions 80-100 mA at 3.0 GeV. This beamline is equipped with a 20-pole, 2 T wigglers, 0.8 mrad beam, and a Si (220) double crystal monochromator that was detuned by 50% intensity downwards. All tests were carried out at 19 ± 7 K with an Oxford Instruments CF1208 continuous-flow liquid helium cryostat. Fine-grained KBr solids were used as reference and were scanned concurrent with each sample. XAS data analysis Athena was utilized for calibration, spectra average, background subtraction and normalization.124 The obtained KCl spectra were used as a reference for Cl K-edge spectra.16 BlueprintXAS version 4.1.4 was applied for peak fitting and quantitative analysis. The fits were run in AUTO mode which uses a Monte Carlo methodology to choose the starting point of each fit and minimize user bias during data workup.108 Computational methods Quantum-mechanical calculations were run using the Gaussian 09 (G09) computational package.35 M06-2X is a decent functional which has been confirmed to have excellent performance in the calculations of intermolecular interactions.127,128 Therefore, all geometry optimizations were performed in G09 using the restricted M06-2X functional with a conductor-like polarizable continuum solvation model (CPCM) of acetonitrile and an ultrafine 110 integration grid. Correlation-consistent double-zeta basis set cc-pVDZ was applied to all atoms except bromine and iodine, which is often recommended for anion and weak interaction calculations.19 The aug-cc-pVDZ-PP basis set is generally used in halogen bond calculations and was applied on bromine and iodine in this study.19,141 All geometries were optimized to a minimum and frequency calculations were performed at the same level of theory to verify the absence of imaginary frequencies. All structures labeled as transition states exhibit only one imaginary frequency. 111 Chapter 5: From XB to ChB: Chalcogen-Containing Chemical Reactions In this chapter, we will investigate two different chalcogen-containing systems which benefit from the presence of ChBs: (1) the modification of inherent sulfur in the petroleum coke (petcoke), known as a common byproduct of oil and gas industry; (2) a hitherto undocumented reaction process of benzisothiazole compounds. 5.1 Nitric Acid Functionalization of the Inherent Sulfur in Petcoke 5.1.1 Background Solid acid catalysts are widely applied in a plethora of synthetic processes in chemical industry, especially for hydration, dehydration, esterification, etherification, alkylation and other acid-promoted reactions.142,143 Carbon-based materials functionalized with sulfonic acid groups have drawn particular attention thereof due to their high stability and accessibility.143 Petcoke, as a final carbon-rich (>80 wt%) substrate from oil refining, is considered as a decent precursor of solid acid catalysis.144 Considering the relatively high sulfur contents (~7 wt%) in petcoke, the further addition of sulfur groups into the carbon framework is not necessary. The functionalization of the inherent sulfur into desired sulfonic acid groups is the focus instead. In collaboration with Dr. Qing Huang in Dr. Josephine Hill group at Department of Chemical and Petroleum Engineering in University of Calgary, we have carried out the mechanistic study of sulfur functionalization in petcoke using nitric acid treatments. 5.1.2 Experimental and Computational Studies of Sulfur Conversion Process The sulfur in petcoke mainly exists in the forms of thiophene (52%), sulfoxide (27%) and inorganic (i.e., sulfur salts, 21%) species, respectively.145 Given that the inorganic sulfur salts are weakly attached to the framework and would be easily washed out, the thiophene and sulfoxide species 112 are intended to be modified and then act as active sites in the solid acid catalysts.146 After the treatment of nitric acid (the typical condition is 80 °C or 120 °C under ambient pressure, and the reaction time ranges from 3 h to 24 h), the formation of sulfonic group -SO3H has been evidenced by X-ray photoelectron spectroscopy (XPS) and esterification reactions which were carried out by Dr. Qing Huang.146 To further probe the mechanistic details of the oxidation pathway and improve the treatment strategy, DFT calculations were employed. Dibenzothiophene (DBT) was chosen as a model compound in the calculations for three main reasons: (1) Thiophene is one of the most common existent forms of organic sulfur in petcoke;143 (2) Compared to sulfoxide, it takes more steps for non-oxidized thiophene to convert into the final sulfonic acid group; investigating the whole pathway of thiophene oxidation would cover the oxidative mechanisms of all existing organic sulfur species in petcoke; (3) The thiophene structures are usually embedded in the carbon substrate. The hypothetic reaction pathway of the oxidation of DBT was adapted from a study by D’Alessandro et al. (see Scheme 5.1).147 DBT was oxidized into dibenzothiophene monoxide (DBTO), dibenzothiophene dioxide (DBTO2) and biphenylsultone (DBTO3) in sequence. In particular, the conversion from sulfone to sultone was proposed as an analogous Baeyer-Villiger oxidation,147,148 during which the electron-deficient sulfur atom was further attacked by oxidizers to form the sultone structure. The DBTO3 is readily collapsed into 2-(20-hydroxybiphenyl)sulfonate (HBPS) in a hydrolysis process. Scheme 5.1 The whole process of sulfur conversion of DBT. 113 5.1.2.1 Oxidation Reactions: from DBT to DBTO3 It is expected that HNO3 or HNO3-derived species are the primary oxidants in the reactions (HNO3, 68% − 70%). Therefore, all possible HNO3-generated oxidative species should be considered, including HNO3 itself, NO3- anion, NO2+ cation, and NO2• radical. From the XPS results, the existence of nitrate groups was verified, supporting that nitration reaction occurred during the acid treatment. It confirms the generation of nitronium ion NO2+ and nitrogen dioxide radical NO2• in the process. The evolutions of those oxidants from HNO3 are demonstrated in Figure 5.1 top.149–151 It is generally believed that the singly-bonded oxygen is the most electron-rich and thus the most reactive part of the above-mentioned molecules in oxidative reactions, which aligns with the Lewis structure of each compound (in Figure 5.1 bottom). Based on the structure of DBT, two types of reactions may occur on the sulfur atom: (1) DBT as electron donor -- the two valence lone pairs of sulfur could act as either electron donors in chemical reactions or binding sites with cations; b) DBT as electron acceptor -- The electron-withdrawing phenyl groups are attached to the sulfur atom and thus generate two “σ-holes” (i.e., areas of positive electrostatic potential) at the extension of C−S bonds (see Figure 5.2). The formed “σ-hole” areas are the potential reaction sites for incoming nucleophiles. The ability for DBT to behave as an electron donor and/or an acceptor strongly relies on the nature of the species with which it encounters. Apparently, the oxidation reactions herein should be induced by the ChB interaction between the lone pairs on oxygen of HNO3-derived species and the formed “σ-hole” areas on sulfur atom. 114 Figure 5.1 Top: Possible conversions of nitric acid in aqueous solution; Bottom: Lewis structures of examined nitrogen-containing species. Figure 5.2 ESP map of DBT showing two regions (labelled as “σ-hole”) of relative positive potential on the covalently bonded sulfur atom. The ESP maps were generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 Two perpendicular perspectives and the corresponding color scale bar are provided for clarity. HNO3 as oxidant The sulfur modification process was first examined using HNO3 as the oxidative reagent. Scheme 5.2 shows how DBT converts to DBTO3 using 3 equivalents of HNO3. Interaction between the nitrogen- and sulfur-containing species was initiated by ChB and subsequently induces single-step oxygen transfer reactions with high activation barriers. Each step 115 is thermodynamically favorable especially for the second and third oxidation reactions, indicating a spontaneous process. The energy barriers for the oxidation of DBT and DBTO are close in energy (57.9 kcal/mol and 57.6 kcal/mol), while the activation energy of DBTO2 (132.2 kcal/mol) is much higher than the previous steps. The third step proceeds via a very unstable transition state that is almost 100 kcal/mol (418.6 kJ/mol) higher in energy than the DBT starting material. The comparison of the three sequential reactions implies that the conversion from DBTO2 to DBTO3 is the rate-limiting step during the sulfonic group formation. Also, it seems extremely hard to overcome the surprisingly high energy barrier of DBTO2 oxidation and this step may require the addition of catalyst. Considering the fact that the trace amount of impurities in petcoke like metal complexes (M = Fe, Co, Ru, etc.) were the common catalysts used in the oxidation of DBT, the activation energies could be lowered with the assistance of those catalysts.147 The metal-complexes-catalyzed mechanisms were not explored in this study. Scheme 5.2 The DFT results showing the oxidative process from DBT to DBTO3 using HNO3 as the oxidant. 116 NO3- as oxidant Given the dissociation of HNO3 in aqueous environment152, NO3- was also considered as a potential reagent in the oxidation process. Nitrate ion is the deprotonated product of nitric acid, therefore behaves similarly as nitric acid in the reaction with DBT. Here, only the first step was examined for comparison. This oxidation reaction is endoergic and has to surpass a fairly high energy barrier (76.7 kcal/mol). Compared to the DBT-HNO3 process, the reaction between DBT and nitrate ion is much less favorable from both thermodynamic and kinetic aspects. It suggests that the measures to avoid the HNO3 dissociation, like keeping the acidic environment by adding H2SO4, will facilitate the oxidation of DBT if oxidation occurs in this manner, which corresponds to the experimental findings. Scheme 5.3 The comparison of NO3- and HNO3 as the oxidant (Note: the first oxidative step was chosen as an example). NO2+ as oxidant Nitronium is usually generated during the protonation or the decomposition of nitric acid. It is extensively used as an active electrophile in nitration reactions where the positively charged nitrogen atom acts as the reacting site. However, both oxygens have two lone pairs which could also be theoretically considered as nucleophiles. The oxidation reactions of DBT using NO2+ as oxidant were investigated (see Scheme 5.4). Compared with HNO3-involved oxidation, the NO2+-induced oxidation process shows significantly lower energy barriers and more 117 thermodynamic benefits. To be more specific, the kinetic barrier is largely decreased to 17.2 kcal/mol even though it sacrifices 6.9 kcal/mol to form the initial binding complex, which is similar to the situation of SN1-a in section 4.2.2. Besides, the produced nitrosonium NO+ reacts readily with water to form nitrous acid, and thus further shifts the equilibrium to the right end. Since the sulfur atom in the reactant DBTO2 is not as approachable as the previous reactants DBT and DBTO (i.e., due to the steric hinderance around sulfur atom), and a concomitant large increase in Pauli repulsion between the reagents (in other words, the positively charged nitrosonium is not a good leaving group), the conversion pathway for the third step was not found unfortunately. Scheme 5.4 The calculation results showing the oxidative process from DBT to DBTO2 using NO2+ as the oxidant. NO2• radical as oxidant A reddish-brown gas was observed during the reaction, which is expected to be the generated NO2• gas. Due to the weakness of N-O bond, NO2• radical is known as a good oxidizer. As illustrated in Scheme 5.5, the energy barrier of each oxidative step using NO2• radical (48.7 kcal/mol, 45.6 kcal/mol, 71.3 kcal/mol) as oxidant is lower than that of HNO3 (57.9 kcal/mol, 57.6 kcal/mol, 132.2 kcal/mol), respectively. All the three steps can proceed with transition states that are <50 kcal/mol above that of the starting materials (DBT + NO2•). Except 118 for the first step which is slightly endergonic, all other steps are thermodynamically favorable. In conclusion, the NO2•-oxidized pathway is kinetically the most accessible among all the evaluated routes. Scheme 5.5 The calculation results showing the oxidative process from DBT to DBTO3 using NO2• as the oxidant. Other possibilities Among the above-mentioned activation energies, some of the numbers are slightly higher than expected, especially for those activation barriers higher than 50 kcal/mol. Therefore, under real experimental conditions, there may exist several possible factors that can effectively lower the activation barriers: (1) As discussed in HNO3 as oxidant session, trace metal complexes may play an important role in catalyzing the DBT oxidation reaction (Note: Petcoke ash content was analyzed by our collaborators. The ash is about 3.7 wt% in the total mass of tested petcoke, in which Al is about 14 wt%, Ti is around 2.5 wt%, Fe 5.4 wt%, Ca 3.4 wt%, Mg 1.2 119 wt%, Na 1.4 wt%, K 2.9 wt%). Considering that some of the metal complexes are embedded in the petcoke framework and are hard to remove by acid pre-treatment, the effect of metal catalysis could not be completely excluded;148 (2) It was reported that HO• radical could be formed during HNO3 decomposition on carbon material surface.153 As a reactive species with strong oxidizing properties, HO• radical can react vigorously with carbon (or even graphitic carbon) in petcoke. Therefore, HO• radical may also facilitate the sulfur oxidation process. 5.1.2.2 Hydrolysis Reactions: from DBTO3 to HBPS In the presence of H2O or OH-, the ring structure of sultone group in the formed DBTO3 could be easily opened and converted to sulfonic group subsequently. In Scheme 5.6, the hydrolysis reaction was calculated. The energy barrier is as low as 8.1 kcal/mol and the Gibbs free energy change of the whole reaction is -18.0 kcal/mol, indicating a favorable process from both thermodynamic and kinetic perspectives. As the reactions were carried out in aqueous medium, the negatively charged hydroxyl group -O- was immediately protonated, thus forming the final product HBPS. Scheme 5.6 The calculation result showing the hydrolysis process from DBTO3 to HBPS-. To better summarize the whole sulfur conversion process, the reaction diagrams of NO2•-oxidized and HNO3-oxidized pathway were shown in Figure 5.3. 120 Figure 5.3 Energy diagram of DBT oxidized by (a) HNO3 and (b) NO2• under standard conditions. 5.1.2.3 Loss of Sulfur After the treatment of nitric acid, the petcoke samples can be utilized as solid acid catalysts in esterification reaction. In this project, esterification of octanoic acid (OA) with methanol was the benchmark reaction for testing the catalytic activities of the acid-functionalized petcoke samples (see chemical equation 2). Herein, sulfonic group is considered as the main active site due to its 121 higher acidity than carboxylic group. Thus, efforts should be made to avoid loss of sulfonic groups and retain active sites. ( 2 ) There are two possible reasons causing the loss of sulfur: (1) In the acid-functionalization process, the petcoke is heated to over 80°C. It is known that the reversible desulfonation reaction usually occurs under heated and acidic environment (The mechanism of desulfonation is shown in Scheme 5.7). Therefore, desulfonation could be a main cause of sulfur loss during the heating reaction. (2) After the acid treatment, the petcoke sample would go through a water-washing step to remove the remaining nitric acid. During the water-washing process, pH of the environment is gradually increasing to neutral, thus more OH- would be dissociated from water. The increasing concentration of OH- may induce SNAr reaction, shown in Scheme 5.8. The exergonic reaction has a relatively high energy barrier of 27.4 kcal/mol at room temperature. In other words, the substitution reaction is spontaneous but proceeding slowly at room temperature. Consequently, a faster water-washing step with acidic environment control is required before drying up. 122 Scheme 5.7 Mechanism of desulfonation reaction. Scheme 5.8 The computational result showing the substitution reaction between HBPS’ and OH-. 5.1.3 Methods DFT calculations were run using the G09 computational package.35 The examined oxidation reactions can be viewed as ChB-induced processes that potentially involve significant contributions from dispersion interaction. M06-2X has been proved to be highly successful in describing dispersion corrections in neutral molecular systems, therefore was used in the DFT calculation.127,154 In radical species, the restricted open-shell formalism was employed using the same functional and basis sets as for other species.155 A balanced polarized triple-zeta basis set def2-TZVP was chosen since it has been commonly applied on light main-group elements and 123 confirmed effective in sulfur chemistry calculation.156 A CPCM of water and an ultrafine integration grid were applied. Geometry optimizations were performed on all species and frequency calculations were performed at the same level of theory to confirm the absence of imaginary frequencies. Transition states were identified and optimized using the quadratic synchronous transit (QST) approach.157 All structures labeled as transition states exhibit one imaginary frequency. 124 5.2 Reaction of 3‑Cl/OMe-Substituted 5‑Nitrobenzisothiazoles and Hydrazine The work in section 5.2 is based on the author’s contribution to a previously published paper.158 Several figures and part of the text were adapted from the paper with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 5.2.1 Background Tetracyclic indole compound 1 (IDC16) has been confirmed to perturb the HIV pre-mRNA alternative splicing, thus effectively blocking HIV replication process.159 The compound library screening of 1 has led to the identification of a novel benzisothiazole-based compound 2 (1C8) which is expected to mimic the anti-HIV activity as IDC16 (see Scheme 5.9 a). To further study the structure-activity relationship of compound 2, an analogous compound 3 was designed, in which the central amide group was incorporated into a more constrained five-membered pyrazolone structure. The comparison between 2 and 3 helps to determine the anti-HIV function of the central amide feature in 2. Based on the reported strategy to establish the pyrazolone ring system, a preliminary synthesis method of compound 3 was envisaged.160 As speculated in Scheme 5.9 (b), 4-chloropyridine-3-carboxylic acid 4 would react with 3-hydrazino-substituted 5-nitrobenzisothiazole 5, followed by a N-methylation reaction of the pyridine nitrogen. We planned to prepare reagent 5 by the C-3 substitution reaction of 3-methoxy- and 3-chloro-5-nitro-benzisothiazoles 6a and 6b with hydrazine. However, 5 was not produced as expected. Instead, rearrangement products 18 and 19 were observed from thin-layer chromatography (TLC), NMR and XRD results (see Scheme 5.10). 125 Scheme 5.9 (a) Structures of 1 (IDC16) and 2 (1C8). (b) Planned synthesis of 3. Numbers in red (structures 6a and 6b) represent the numbering system for the benzisothiazole ring. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. Scheme 5.10 Unexpected reaction course from 6a/6b to 18/19. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. In this section, mechanistic pathways for the formation of 18 and 19 were proposed and thoroughly examined using DFT methods. The interplay of the possibly involved weak interactions has also been deconvoluted as follows. 126 5.2.2 Computational Studies of the Proposed Reaction Mechanism The originally planned route to 3 was logical in that 3-OMe/Cl benzisothiazoles can give the expected C-3 substitution product in the presence of amine nucleophiles.161–164 Nevertheless, the adjacency of the N and S atoms in the five-membered isothiazole ring may complicate its reactivity, making it difficult to predict the reaction outcome.165 In literature,161 3-chloro benzisothiazole 7 can react with amines in two ways: (1) SNAr-type substitution pathway to afford 3-amino benzisothiazole 8; (2) SN2 reaction at the covalently bonded S atom leading to the cleavage of the weak S−N bond and the formation of benzonitrile compound 10 after eliminating Cl-. The disulfide complex 11 was also observed in the products due to the dimerization of two identical molecules 10. It was also documented that the reaction of 7 would become complicated in the presence of piperazine.166 High yield of ring-opened compound 12 was observed when the reaction was heated at 65 °C, which is a product of SN2 reaction. If heated at a higher temperature (165 °C), the nucleophile piperazine would further react with the cyano group in 12 to give a presumed intermediate 13, which undergoes ring closure to give 3-piperazino 14, i.e., the overall product of direct SNAr substitution (as shown in Scheme 5.11). Scheme 5.11 Competing SNAr and SN2 reaction pathways for the reaction of benzisothiazoles with nucleophiles. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 127 It was reported that the preparation of 3-hydrazinobenzisothiazole 16 (SNAr product) can also be achieved by reaction of 3-methoxybenzisothiazole 15 with excess hydrazine (6 equiv.) in refluxing ethanol (EtOH) for 30 min.167,168 Both 16 and 17 were recrystallized and isolated from ethanol. In our trials, 17 was successfully prepared as yellow crystals. However, 16 was undetected in the reaction of 15 with excess hydrazine, and disulfide 11 (72%) was the only isolable product instead (see Scheme 5.12 a). Scheme 5.12 (a) Reaction of 15 with hydrazine and phenyl- hydrazine. (b) Conversion of 5-nitrobenzisothiazoles 6a and 6b to rearrangement products 18 and 19, respectively. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 5.2.2.1 The Reaction of 5-Nitro-3-Methoxybenzisothiazole 6a If the reactants 7 and 15 were slightly modified, in which an additional nitro group was attached to the aromatic system, the reactions took an unexpected course. 5-nitro-3-methoxybenzisothiazole 128 6a and hydrazine produced neither hydrazine substitution product 5 nor ring-opened disulfide product 11 based on the results of TLC and 1H NMR. The only “nonpolar” component detected by TLC (96/4 DCM/MeOH) and isolated in 76% yield by recrystallization from MeOH was hydrazonate compound 18 [(Z)-methyl 2-amino5-nitrobenzohydrazonate], which was also confirmed by single-crystal XRD (see Scheme 5.12 b). The structural comparison of reactant 6a and product 18 may provide some useful clues concerning why 18 was formed: (1) The isothiazole ring was opened; (2) The sulfur atom was replaced by an amino group; (3) The presumed methoxy leaving group at C-3 position was maintained; such observation was also confirmed by the absence of any OMe → OEt exchange in the 1H NMR spectrum of the crude product mixture when the reaction of 6a with hydrazine was carried out in EtOH as the solvent. Those features suggested that the formation of 18 involves a ring opening at the N−S position in the reactant 6a. The sulfur atom in 6a was simultaneously bonded to a nitrogen atom with much higher electronegativity and an electron-withdrawing nitrobenzo group, leading to its most vulnerable site in 6a when approaching a nucleophile. This is also evidenced by the ESP map of 6a (Figure 5.4), in which there exist two σ holes on the extension of C−S bond and N−S bond, respectively. Furthermore, the electrostatic potential at the extension of N−S bond is much higher than that at the C−S axis. It is reasonable to infer that the ChB formed between the sulfur atom and hydrazine at the extension of N−S bond would induce the formation of -SNHNH2 group and the dissociation of the old N−S bond in 6a. The attack of hydrazine at the sulfur atom affords imidate anion 21 (Scheme 5.13). The negatively charged N atom is very reactive so that it may either eliminate methoxy group to give a cyano function, or an alternate reaction process leading to formation of nitro group stabilized bicyclic Meisenheimer complex 22. Considering that the -OMe is retained in the product 18, it is more likely to go through 129 the latter path. In essence, this transformation corresponds to the first step in an intramolecular SNAr reaction.169,170 A neutral aza-bicyclo-[6,4] compound 23 is expected to form after the dissociation of NH2NHS− in 22. Although bicyclic compound 23 is considered as a formally anti-aromatic (4n electron) species with inherently high strains and reactivity, the parent compound, 7-azabicyclo[4.2.0]octa-1(6),2,4,7-tetraene, missing the -OMe and -NO2 substituents, is a known compound with a measurable lifetime.171 In the final steps of the rearrangement pathway, 1,2-addition of hydrazine to the “imine” carbon in 23 to generate 24 would set the stage for participation of the lone pair of electrons on the hydrazine nitrogen in opening of the strained four-membered (1,2-dihydroazete) ring and formation of observed product 18. Figure 5.4 The electrostatic potential map of 6a. The ESP map was generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 130 Scheme 5.13 Proposed mechanism for the conversion from 6a to 18. The pivotal Meisenheimer intermediate is highlighted with brackets. To support the proposed mechanism, DFT calculations were carried out. The susceptibility of the C-3 center and the sulfur atom in the presence of hydrazine were both taken into account. Therefore, three different pathways were examined in Scheme 5.14, respectively: (1) the stepwise process in which ring opening produces methoxyimidate 21 and SNAr process to give Meisenheimer complex 22 (P1 pathway); (2) A concerted process during which S-N bond cleaves and N-C bond forms at the same time, leading to compound 22 directly (P2 pathway); (3) One equivalent of hydrazine attacks the C-3 position, followed by another equivalent binding to the sulfur atom, leading via a stepwise process analogous to P1 to the formation of an alternate Meisenheimer complex 27. (PC pathway) 131 Scheme 5.14 Three proposed pathways in which hydrazine reacts with 6a. The colored arrows represent a thermodynamic change in the first step for each pathway. Red represents an endergonic process, while green signifies an exergonic step. The relative Gibbs energy of each stage (compared to the initial reactants) is indicated in parentheses (units of kilocalories per mole). First of all, two types of reactions (i.e., substitution reaction vs. addition reaction) are compared from thermodynamic perspectives. As illustrated in Figure 5.5 (note: since P2 is basically P1 in which 22 is directly formed without going through 21, only P1 and PC pathways are shown), 6a would react to give 24 before collapsing to the final product 18 in either P1, P2 or PC pathways. In terms of P1, 6a would convert to an isoenergetic ring-opening intermediate 21 preceding to a relatively unstable Meisenheimer complex 22 (∆G0 = +13.4 kcal/mol). The succeeding dissociation of -SNHNH2 group leads to a more thermodynamically favorable compound 23 (∆G0 = -35.7 kcal/mol). In contrast, PC pathway is predicted to undergo an endergonic process in the first step (from 6a to 25 ∆G0 = +16.0 kcal/mol), a subsequent stabilization at 26 (∆G0 = +4.6 132 kcal/mol) and went through another endergonic step to 27 (∆G0 = +10.8 kcal/mol). Those energy values suggest that the substitution reaction (P1 or P2) is more accessible to the addition reaction (PC pathway). Furthermore, if 26 is produced, the exocyclic carbon attached with three heteroatoms would enable the loss of the methoxide and formation of imodyl hydrazide 30 (the structure of 30 is in Scheme 5.16) rather than Meisenheimer complex 27. In this case, the experimentally observed product 18 would not be produced. Figure 5.5 Reaction coordinate diagram of P1 and PC in the 6a reaction system. The total Gibbs energy of all reactants was set as the baseline (0 kcal/ mol). Each plateau represents the total Gibbs energy of all existing compounds (i.e., reactants and products) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. The requisite transition states for pathways P1 and P2 were further explored to evaluate feasibility. The transition states (i.e., 6a → 21: 25.8 kcal/mol; 21 → 22: 30.2 kcal/mol) for stepwise P1 have been optimized and validated as shown in Figure 5.6, both falling into accessible energy ranges. The calculated numbers are slightly higher than expected, which implies a possible 133 pathway catalyzed by methanol and hydrazine simultaneously in such protic media. Unfortunately, the transition state in the concerted process P2 has not been successfully resolved after all attempts. All trials have invariably collapsed to structures along the stepwise P1 pathway. Therefore, it is reasonably surmised that either the P2 pathway is nonexistent, or its energy barrier is much higher than that in P1 pathway. Figure 5.6 Reaction coordinate diagram of the first step in P1 and P2 in the 6a system. The pink area represents an approximation of where the transition state in the P2 pathway lies. The total Gibbs energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs energy of all existing compounds (i.e., reactants, transition state TS, and products) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 5.2.2.2 The Reaction of 3-Chloro-5-Nitrobenzisothiazole 6b In the reaction of 3-chloro-5-nitrobenzisothiazole 6b with excess of hydrazine (≤6 equiv.), a polar mixture of multiple inseparable compounds was produced. If the amount of hydrazine was decreased to ≥0.5 equiv and diisopropylethylamine was added as a base, nonpolar product 19 was 134 separated after column chromatography in ≤33% yield, which was confirmed by single-crystal XRD. According to the 1H and 13C NMR spectra of 19, we inadvertently found that it corresponded to the same compound obtained in a separate experiment in which 6b was reacted with 4-pyridinone amine 20 (see Scheme 5.12 b). In the ESP map of reactant 6b (Figure 5.7), the two σ holes on the surface of sulfur atom were observed that are similar to those in 6a. The σ hole on the extension of C-Cl bond was also visible but with low magnitude in that Cl has a slightly higher electronegativity than C. That’s why the area around C-3 position is of intense positive electrostatic potential, which is not noticeable in 6a as shown in Figure 5.4. Two potential reactive sites stand out herein: (1) reacting at sulfur atom which can be induced by ChB; (2) attacking the C-3 position where it shows high electrophilicity. Figure 5.7 The electrostatic potential map of 6b. The ESP map was generated with Gaussian09 using the M06-2X functional and def2-TZVP basis set and visualized by WebMO.35,37 One of the common features in rearrangement compound 18 and 19 is that the nitrogen atom migrated to the para position of the -NO2 group. It indicated that a Meisenheimer-type intermediate similar to 22 was generated during the process. However, the molecular structure of 19 is more complicated than 18 in several different aspects: (1) The 3-chloro in the starting material is missing 135 in the product; (2) A sulfur atom is inserted into the 2,1-benzisothiazole ring system; (3) An additional sulfur atom serves as a bridging atom between two 2,1-benzisothiazole fragments. Based on the structural analysis of both reactants and products, three plausible pathways were proposed (see Scheme 5.15). In P1 pathway, the sulfur atom is attacked by hydrazine and thus induces the fracture of N-S bond. The generated 3-chloroimidate species was transient (i.e., the optimized stable form of it could not be found in the DFT calculations) that readily loses the chloride to give a very stable benzonitrile compound 28 (∆G0 = -61.4 kcal/mol). In the alternate concerted pathway P2, the N−S bond (in the 2,1-benzisothiazole ring) dissociation and the N-C bond formation occur simultaneously, directly forming a Meisenheimer complex 29. This step is similar to the conversion from 6a to 22, which is an endergonic process (∆G0 = +14.0 kcal/mol). If hydrazine attacked the C-3 position, SNAr process was predicted to occur instead of addition reaction, since chloride is a better leaving group than methoxide. Surprisingly, this step is even more exergonic (∆G0 = -79.9 kcal/mol) than the first step in P1. Therefore, P1 and PC are much more favorable than P2 in terms of the first step. 136 Scheme 5.15 Proposed P1, P2 and PC pathways for reaction of hydrazine with 6b. The colored arrows represent thermodynamic changes in the first step for each pathway. Red represents an endergonic process, while green signifies an exergonic step. The Gibbs energy change is indicated in parentheses (units of kilocalories per mole). To further evaluate the feasibility of P1 and PC, the kinetic comparison is illustrated in Figure 5.8. The energy barrier in the first step of P1 is as low as 5.6 kcal/mol, though the transition state in either manifold is accessible. According to the comparison in Scheme 5.15 and Figure 5.8, it is concluded that the PC is superior to P1 both thermodynamically and kinetically. The proposed compound 5 would go through more steps to form the desirable product 19. The envisaged mechanism is drawn in Scheme 5.16. An additional equivalent of hydrazine reacts with compound 5 to give a ring-opened intermediate 30, which is converted to a Meisenheimer complex 31 afterwards. At this point, it was anticipated that the neutralization of 31 must occur in a way that permits conservation of the sulfur atom present in the isomeric 2,1-benzisothiazole components in 137 19. Indeed, in contrast to the reactivity of complex 22, which loses the SNHNH2− anion to rearomatize the phenyl ring, a [1,3]-migration (or [1,7]-migration of the −SNHNH2 motif in 31) was envisaged to occur giving [4,6]-bicyclo compound 32. Such migrations of sulfur are known,172 and in the case presented here, this leads to formation of 32 in an overall “energy equivalent” process. The following steps leading to 2,1-benzisothiazole 34 would involve ring closure to tricyclic species 33 (Note: this step would release an equivalent of hydrazine), bond reorganization, and ring expansion. Both steps were predicted to be highly exergonic and/or energetically favorable. Unfortunately, the detailed mechanism behind the introduction of sulfur bridge remains unknown currently. A more intuitive summary of the whole process is shown in Figure 5.9. Figure 5.8 Reaction coordinate diagram of the first step in P1 and PC reaction modes of 6b with hydrazine. The total Gibbs free energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs free energy of all existing compounds (i.e., reactants and transition state TS) at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 138 Scheme 5.16 Predicted pathway from 3-hydrazino-5-nitrobenzisothiazole 5 to isomeric 2,1-benzisothiazole intermediate 34. To better compare the energy of each compound, two states of hydrazine were used (NH2NH− and NH2NH2). The Gibbs energy change between the reactant and product in each step is indicated in parentheses (units of kilocalories per mole). Red represents an endergonic process, while green signifies an exergonic step. The formed pivotal Meisenheimer intermediate is highlighted with brackets. 139 Figure 5.9 Reaction coordinate diagram for the conversion of 6b to pivotal 2,1-benzisothiazole compound 34. The total Gibbs energy of all reactants was set as the baseline (0 kcal/mol). Each plateau represents the total Gibbs energy of all existing compounds at each stage. This graph is adapted from paper [158] with permission from J. Org. Chem. 2021, 86, 9, 6381–6389. Copyright © 2021, American Chemical Society. 5.2.3 Methods The author was responsible for the computational part in this project. DFT calculations were performed using the G09 computational package.35 M06-2X has been proved to be highly successful in describing dispersion corrections in neutral molecular systems, therefore was used in the DFT calculation.127,154 A balanced polarized triple-zeta basis set def2-TZVP was chosen since it has been commonly applied on light main-group elements and confirmed effective in sulfur chemistry calculation.156 Therefore, all geometry optimizations were performed in G09 using the restricted M06-2X functional and the def2-TZVP basis set.173,174 The LC-ωPBE functional with dispersion correction was used to validate M06-2X results.175 [To further validate the feasibility of the M06-2X functional, a different functional that explicitly considers dispersion corrections 140 was used to examine an exemplary reaction (6a to 22 process). There were no substantial changes in the results using the LC-ωPBE functional with dispersion correction.] A CPCM of methanol and an ultrafine integration grid were applied. All geometries were optimized to a minimum, and frequency calculations were performed at the same level of theory to verify the absence of imaginary frequencies. Geometry optimization of transition states was employed using the QST approach.157 All structures labeled as transition states exhibit one imaginary frequency. Intrinsic reaction coordinate calculations were carried out to ensure transition states connected the appropriate local minima.173 5.3 Conclusion In this chapter, two sulfur-containing systems have been studied: (1) In the petcoke modification project, it is revealed that the sulfur oxidation reaction can be induced by ChB between electron-deficient sulfur and surrounding nucleophiles. Successive oxidation reactions depend on both the interaction strength between sulfur and oxidizer and the altering steric hinderance. DFT calculations have explored the whole process of sulfur modification during the acid treatment of petcoke, which have also provided insightful guidelines for improving the experimental operations. This study enables the modified petcoke to act as a solid acid catalyst for esterification reactions. (2) With the assistance of DFT methods, we have demonstrated new and novel chemistry in the conversion of 3‑Cl/OMe-substituted 5‑nitrobenzisothiazoles to the isolated rearrangement products, which also involves ChB. Meisenheimer complexes have been confirmed to be an important intermediate during the course of the reaction, which is produced after the ChB-initiated cleavage of N−S bond. The entanglement of chlorine, sulfur, methoxy, phenyl and nitro group has substantially complicated the reactions. The adjacency of sulfur and other electron-withdrawing groups makes it more vulnerable during the process. 141 Electrostatic potential analysis and the σ-hole theory were used to predict the potential reactive sites which have induced ChB in both scenarios. Covalent contributions thereof were not investigated due to the complexity of each system. The generated ChBs have established a favorable geometry of reacting species before electron flows in chemical reactions. To be more specific in this chapter, ChB can be an effective trigger of either oxidation reactions or substitution reactions in sulfur chemistry. 142 Chapter 6: Conclusion and Future Directions 6.1 Thesis Summary In this thesis, a systematic study on partially covalent weak interactions has been conducted in an effort to: (1) establish a comprehensive characterization methodology for SBIs; (2) provide holistic perspectives on SBIs (i.e., not merely focus on the electrostatic component); (3) bridge the gap between fundamental studies and applications; (4) guide for a more rational design of SBIs-involved chemical systems. In chapter 2, a series of hypervalent halogen (III) adducts have been selected to investigate the nature of XBs. Geometric properties were revealed by single crystal XRD. XAS, in combination with computational methods, has illustrated the electronic structures of XBs. The entanglement of both σ and π interactions was observed in DPI-Cl compounds, which is unusual among selected hypervalent systems. Based on the established methodology in chapter 2, the degree of charge donation in ChB interactions was probed in chapter 3. This is the first experimental evidence for ChB covalency in ionic complexes. XB and ChB with relatively weaker binding strengths have shown higher covalent contributions than their counterpart HB. Different substituents were confirmed to influence both the binding strength and the degree of charge transfer in ChBs. The simultaneous involvement of σ- and π-manner characters has also been noticed in 2_ChB_Cl adduct. The work in chapter 4 has extended the fundamental research into a more appliable scenario. A XB-catalyzed benchmark reaction was chosen to study how XB can affect a chemical reaction course. With Cl and Br K-edge XAS, we have confirmed that halogenated activators would bind to both substrate and product and thus facilitate the process in a more kinetically and 143 thermodynamically favorable manner. DFT calculation has also validated the SN1-type reaction pathway. Chapter 5 has reported two collaborative projects: (1) Petcoke modification -- during the process of petcoke modification using acid treatment, the sulfur species embedded in carbon substrate has undergone a series of oxidation reactions to form a final product sulfonate. A ChB-initiated oxidative pathway has been verified using DFT methods. According to the mechanism, many factors should be considered in the experiment. For example, maintenance of acid environment and involvement of nitration reaction can both facilitate the sulfur oxidation process as they have increased the electrophilicity of sulfur and also the binding strength of formed ChBs. (2) Nitrobenzisothiazole conversion -- we have illustrated the mechanism of 3-Cl/OMe-substituted 5-nitrobenzisothiazoles reacting with hydrazine. Different substituents, competition with XB, and solvent effect all have impacts on the induced ChBs. The generated ChBs on sulfur atoms have then triggered a succession of chemical reactions. In summary, we have first denoted a partially covalent picture of weak interactions in chapter 2 and 3, which is more appropriate than describing them as a set of non-covalent interactions driven by electrostatics. In chapter 4 and 5, the importance of such SBIs haven been evidenced within several representative chemical reactions. In those applications, our scope is not only confined to the SBIs themselves, but also expands to their relationship with the whole reaction environment. 6.2 Future Directions However, there are still many interesting topics to be explored based on our current studies. It is concluded in chapter 2 that the structural flexibility has a big impact on the nature of induced XBs. Other effects, like different substituents or multiple binding sites, are not yet discussed. The model system in chapter 2 is a good starting point from which we can synthesize a new set of 144 potential XB adducts. According to chapter 2 and 3, the simultaneous entanglement of σ and π interactions was observed in both XB and ChB systems, but the π interaction was not exclusively resolved. In our future studies, new XB or ChB model systems can be utilized in which the σ and π interactions act individually. In this case, the effect of σ and π characteristics on weak interactions can be investigated separately. Furthermore, we have mainly focused on the fundamentals of weak interactions at the atomic level. More macroscopic properties of those compounds can also be examined, such as conductivity (or impedance) in different directions and electrochemical performance under different conditions (Though the macroscopic properties can be predicted by the molecular properties. For instance, the efficient charge transfer among the molecules can lead to a high conductivity of the established materials). The functions of XB interactions in solution have been explored in chapter 4, yet the solvent effect was not thoroughly tested. In future studies, XB-catalyzed reactions could be carried out in different solvent environments, including protic/aprotic and polar/non-polar solvents. The catalytic performance under different conditions will provide useful guidelines for the solvent selection in weak-interaction-catalyzed systems. In chapter 4 and 5, the studied applications are mainly in catalytic and synthetic fields. It will be very interesting to explore possible applications of those partially covalent SBIs in other areas such as molecular electronics, and quantum qubits. In the long run, the feasibility of integrating those weak-interaction-established compounds into an electronic device should be examined in collaboration with chemical engineering groups. In this thesis, we have focused on iodine-, bromine-, or chlorine-involved halogen bonding, but the fluorine-centered XBs have not been investigated. Due to the extremely high electronegativity of fluorine, it is difficult to establish halogen-bonding systems with fluorine as the electron acceptor. Efforts should be made to modify the fluorine-containing Lewis acid in order to deplete 145 the electron density from fluorine. Introducing electron-withdrawing substituents or cationic backbone is the most prevailing method. In the future studies, possible candidates (such as N-fluorobenzenesulfonimide, selectfluor and 1-fluoropyridinium salts) can be adapted to study XBs with fluorine atom as electron acceptor. The above-mentioned studies are intended for a more rational design of the weak-interaction-assisted systems in many fields, such as catalysis, synthesis, anion recognition, and molecular electronics. To be more specific, the enhancement of covalent contribution in weak interactions has been confirmed to be critical during the process of catalyzed bond cleavage; then we should focus on a better energy match and orbital overlap when designing the weak-interaction pairs (since the related study is still in its infancy, a step-by-step guideline for the molecular design is to be developed); the solvent effect, concentration effect, and interaction competition are also decisive if a successful catalytic system is to be established. Such workflow can also be applied in weak-interaction-assisted synthesis. In terms of anion recognition, covalent contribution between ion pair is crucial if a highly selective ion-assembly is desired. Firstly, we can inspect the orbital interactions between ion pair using molecular orbital analysis; based on the orbital analysis, substituent change, geometric optimization, or the alteration of active site could be carried out to improve the charge-transfer character in weak interactions. The scenario in molecular electronics is more complicated than the previous applications. The degree of charge transfer and the efficiency of charge transfer are both important in molecular electronics. On one hand, efforts should be made to enhance the degree of charge transfer in weak interactions; on the other hand, a clearer understanding of σ and π interactions is necessary. 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Online 66, o486–o486 (2010). 158 Appendices Appendix A Investigation on Halogen Bonding in Substituted 1-Methylpyridinium Systems with One Interaction Site A.1 Background This project was carried out with the assistance of two visiting students in the Kennepohl group (Kerstin Rickmeyer and Usman Jamshed) In this system, the Lewis base is electrostatically activated by a cationic pyridinium ring. A series of these acceptors that can act as both σ and π acceptors were designed and synthesized (see Figure A.1). 2-halo-1-methylpyridin-1-ium is named M2XP (X = Cl, Br, I, respectively), while 4-halo-1-methylpyridin-1-ium is named M4XP. These cationic pyridinium salts (triflate as counterion) are expected to be sufficiently electron-poor to allow for strong XB interactions and depletion of charge at the halogen acceptor is likely to facilitate formation of π interactions with an appropriate donor. Figure A.1 Substituted 1-Methylpyridinium salts (triflate as counterion) as electron deficient XB acceptors. The left compound is named M2XP-OTf; the right is called M4XP-OTf. In order to investigate XB interactions with adequate bond strength, two different types of XB donors were examined (see Figure A.2). Firstly, a series of tetra-n-butylammonium halide salts 159 (i.e. TBAF, TBACl, TBABr, TBAI) were used as a source of halide donors which can act as both σ and π donors. Alternatively, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) was used as a Lewis base with σ donor and π acceptor character. Figure A.2 Proposed equilibrium for the interaction between halogenated pyridinium molecules and two different types of XB donors: (a) halogen ions (i.e., Y-); (b) TEMPO. A.2 Results - Halide Ion as XB Donor Spectroscopic results To examine an appropriate XB binding site in the formed adduct, single crystal X-ray crystallography was employed. Crystals of M4BrP (Fig. A.3a) and M2BrP (Fig. A3b) with bromide as a counterion were obtained by recrystallization of the pyridinium salt with TBABr. In the crystal structures, the Br– is located around the bromine atom of the pyridinium ring as desired but not near the N+, which would be another possibility. As shown in table 1, the bond distance between two halogen atoms is well below their sum of van der Waals radius, and the C-Br···Br angle is fairly close to 180 degree, both of which indicate that we obtained expectant XB adducts. 160 Figure A.3 Single crystal structures of M4BrP (a) and M2BrP (b) with bromide as counterion. Table A-1 Metric parameters from all crystal structures. Structure r(Br-Br) (Å) rvdW(Br-Br) (Å) α(C-Br-Br) (°) M4BrP∙∙∙Br 3.263 3.700 170.5 M2BrP∙∙∙Br 3.342 3.700 172.4 Solution NMR-based techniques have provided considerable insights into interaction-induced changes.176 In our work, 1H NMR was used to monitor the formation of halogen bonds between each synthesized pyridinium salt and halide ion. Compared with brominated and iodinated pyridiniums, the spectral changes in chlorinated ones before and after the addition of halide ions are remarkable. In the system shown in Fig. A.4, for example, significant changes of chemical shift (∆δ) in M2ClP are only observed for Hb, the proton adjacent to the chloride that participates in the XB. Similar phenomena were observed in all the other studied pyridiniums. This may be explained by the fact that 1H NMR can only detect interactions two to three bonds away from the interaction site. Considering that the comparably large distance of the reporter nucleus from the halogen atom directly involved in XB decreases the magnitude of the detectable chemical shift change and diminishes the accuracy of the data, only the ∆δ of Hb was focused. Fig. A.5 shows a plot of the 1H NMR chemical shift change of Hb in each studied pyridinium salts upon addition of different halide ions (ratio is 1:1). With the exception of F-, the ∆δ of Hb become less and less pronounced from Cl- to I- in all the tested pyridinium salts. And the chemical shifts of protons are 161 more affected by halide ions in chlorinated pyridinium than brominated and iodinated ones. This can be attributed to the increasing polarizability from chlorine to iodine. The exceptional behavior of fluoride is explained by its crystal structure in Figure A.6. It indicates that F- is so reactive that can easily bond to the silicon atoms from glassware and other sources (The original reagent TBAF was absorbed on silica gel), leading to the absence of free F- in the solution. Figure A.4 Comparison of 1H NMR (400 MHz) spectra of M2ClP mixed with different halide ions. Data was obtained for 1:1 mixtures of pyridinium and halogen ion, in acetonitrile-d3 at 25 °C. 162 Figure A.5 The experimentally observed 1H NMR chemical shift alteration for Hb in each studied pyridinium upon addition of halide ions, using the Hb chemical shift of free pyridinium as a reference for the unbound state. Data was obtained for 1:1 mixtures of pyridinium : halogen ion, in acetonitrile-d3 at 25 °C. Figure A.6 Crystal structure of M2ClP/F- complex. It is worth mentioning that in the brominated and iodinated pyridinium systems, new peaks emerge when Cl- is added (Fig. A.7). The unexpected outcome may be caused by undesired substitution reactions in the solution, the hypothesized mechanisms of which are shown in Figure A.8. The proposed mechanism is further supported by XAS spectra, as shown in Fig. A.9. The disappearance of the pre-feature when additional Cl- is present M2BrP solution indicates that the 163 covalently bonded bromine on the aromatic ring is replaced by chlorine and presents as free Br- in the solution. Figure A.7 Comparison of 1H NMR (400 MHz) spectra of M2BrP mixed with different halide ions, in which new emerging peaks are circled. Data was obtained for 1:1 mixtures of pyridinium and halogen ion, in acetonitrile-d3 at 25 °C. Figure A.8 Proposed mechanism for the nucleophilic aromatic substitution when adding Cl-. Figure A.9 Br K-edge XAS spectra of M2BrP upon addition of Cl-. 164 Computational results Other than the aforementioned experimental structural determination, the electronic changes of studied XB systems were further examined by DFT calculation (with restricted functional). In all the studied systems, the carbon-halide (C-X) bond distance was shown to increase in the presence of XB. The increase in bond length implies the weakening of the C-X bond due to the formation of XB. The change in Gibbs free energy of XB formation ∆Gf for each system is shown in Table A-3. These values indicate that formation of these XBs is thermodynamically favoured. It is also apparent that a stronger XB is expected to form in the M2XP system than in the M4XP system, which generally corresponds to the trend of the NMR chemical shift alteration. Table A-2 Calculated C-X bond length increases in the studied systems C-X bond length increase F- Cl- Br- I- M2ClP 20% 9.9% 16% 16% M4ClP 16% 3.6% 5.2% 1.6% M2BrP 12% 5.5% 7.9% 7.2% M4BrP 7.5% 3.3% 4.4% 3.6% M2IP 12% 6.3% 8.3% 8.1% M4IP 8.2% 4.1% 5.3% 4.9% 165 Table A-3 Calculated ∆Gf by forming XB in the studied systems ∆Gf (kcal/mol) F- Cl- Br- I- M2ClP -52.68 -4.870 -6.487 -3.302 M4ClP -45.82 -3.397 -4.695 -2.263 M2BrP -59.38 -7.986 -10.06 -5.495 M4BrP -52.94 -6.056 -7.676 -4.050 M2IP -67.75 -11.34 -14.46 -8.341 M4IP -60.48 -8.743 -11.32 -6.172 A.3 Results - TEMPO as XB Donor The extremely weak interaction between TEMPO and neutral halogenated molecules has been reported by Mugnaini et al., which urges us to strive for a stronger XB in radical systems.177 To the best of our knowledge, TEMPO interacting with cationic halogenated molecules, which are expected to form stronger XB, has never been investigated so far. Therefore, in this part, we focus on the nature of XB formed between TEMPO and the above synthesized pyridinium salts. Spectroscopic results Like halide donors, TEMPO has little to no effect on the pyridinium protons besides Hb. Figure A.10 shows a plot of the Hb chemical shift change (∆δ of Hb) in each studied M2XP system in the presence of TEMPO of different ratios (TEMPO:M2XP = 0:1, 1:1, 2:1, 5:1 and 10:1). The changes of 1H NMR spectra of chlorinated pyridiniums are larger than those of their brominated and iodinated analogues. Chlorinated pyridinium system is again illustrated as an example (Fig. A.11). In contrast to the downfield shifts seen in the 1H NMR spectra of systems in which halides act as the donor, the chemical shift δ of Hb shifts further upfield as the concentration of TEMPO in solution increases. 166 Figure A.10 The experimentally observed 1H NMR chemical shift alteration for Hb in each studied M2XP system upon addition of TEMPO of different ratios (TEMPO:M2XP = 0:1, 1:1, 2:1, 5:1, and 10:1), using the Hb chemical shift of free pyridinium as a reference for the unbound state. Data was obtained in acetonitrile-d3 at 25 °C. Figure A.11 Comparison of 1H NMR (400 MHz) spectra of M2ClP mixed with TEMPO. Data was obtained for different ratio of TEMPO and M2ClP, in acetonitrile-d3 at 25 °C. Next, we tried to separate the binding and non-binding states in 1H NMR spectra under lower temperature, but we failed to get the splitting of the featured peak even under low temperature (Fig. A.12 a). Similar to the results shown in Fig. A.11, the △δHb doesn’t reach an equilibrium, even when the temperature is lowered down to -35°C. This indicates a relatively small binding constant of the formed XB complex (Fig. A.12 b). Cl K-edge XAS has also been applied for 167 inspecting the discrepancy between binding and non-binding states. No edge shift or pre-feature has been observed from the spectrum (Fig. A.13), again implying a fairly weak interaction in this system. Figure A.12 (a) Comparison of 1H NMR (400 MHz) spectra of M2ClP mixed with TEMPO (1:1 ratio). Data was obtained at different temperature (25°C, 15°C, 0°C, and -35°C), in acetonitrile-d3; (b) chemical shift alteration for Hb in M2ClP system upon addition of TEMPO (TEMPO:M2XP = 1:1) at different temperature, using the Hb chemical shift of free pyridinium as a reference for the unbound state. Figure A.13 Cl K-edge XAS spectra of M2ClP(a) and M4ClP(b) upon addition of TEMPO. Computational results DFT calculations (shown in Table A-4) were used to examine the theoretical structural and energy differences in each system. Because TEMPO is a radical, an unrestricted functional was used. The magnitude of calculated changes of Gibbs free energy ∆Gf 168 in this system are generally lower than that in the halide ion system. This indicates a relatively smaller equilibrium constant K in Figure A.2(b) than that in Figure A.2(a), which is also supported by the small chemical shift alteration of Hb even in the presence of largely excessive TEMPO. Table A-4 Calculated C-X bond length increases and ∆Gf in all the studied XB systems M2ClP M4ClP M2BrP M4BrP M2IP M4IP C-X Bond Length increase 0.56% 0.17% 0.42% 0.26% 0.66% 0.61% ∆Gf (kcal/mol) -7.233 -6.191 -5.037 -5.656 -5.615 -5.722 A.4 Comparison of Results from Two Different Donors The results from two different donor systems manifest both similarity and difference. In 1H NMR spectra, the Hb chemical shift has the most apparent variation on account of its closest position to the XB interaction site. While the direction of chemical shift change is coincidently opposite in the two systems. It is commonly acknowledged that variations in chemical shifts are usually ascribed to the electron population of the respective atom, i.e., to shielding or deshielding.178 The downfield alteration in halide ion system implies the XB formation results in a more deshielding environment at Hb. By the same token, the XB interaction leads to a more electron-rich environment at Hb in TEMPO system, but the detailed mechanism is still under investigation. In the Cl and Br K-edge XAS spectra, no evident edge shift or pre-feature has been observed in either system, indicating relatively weak XB formed with only electrostatic interaction but no partial covalency present. 169 A.5 Methodology Synthetic methods: As shown in schemes 3 and 4, the six different XB acceptors were synthesized using known methods.179–181 All synthesized pyridinium salts were characterized by NMR spectroscopy and FT-IR spectroscopy to ensure the desired structure and purity. All the aforementioned XB donors were purchased from Sigma Aldrich and used without purification. Figure A.14 Synthesis of the ortho substituted XB acceptors. Figure A.15 Synthesis of the para substituted XB acceptors. Spectroscopic methods: In order to gain structural information about the formed complexes, single crystal X-ray diffraction was used. The behaviors of halogen bonds in different systems were studied with the assistance of NMR and XAS. Computational methods: Quantum-mechanical calculations were run using the G09 computational package.35 All geometry optimizations were performed in G09 using the B3LYP functional with a radii and non-electrostatic solvation model of acetonitrile; an ultrafine integration grid; and the 3-21G basis set.182,183 The changes of Gibbs free energies ΔGf were estimated using the following formula: ∆𝐺! = 𝐺-. /012345 − (𝐺-. 60708 + 𝐺-. 9//42:08) ( 3 ) Where GXB donor and GXB acceoptor are the Gibbs free energies of the isolated donor and acceptor molecules, respectively; GXB complex is the Gibbs free energy of the interacting pairs. 170 Appendix B Investigation on Halogen Bonding in Substituted 1-Methylpyridinium Systems with Two Interaction Sites B.1 Background Hydrogen bonding is an indispensable interaction in many biological systems. For instance, nucleic base pairs are held together by hydrogen bonding which have established the structural basis of DNA.184 Though halogenated molecules are less common in those biological systems, molecules containing halogens have already been applied in drug development and disease treatment.185,186 It is therefore reasonable to anticipate the involvement of XB in those systems. Scientists have revealed that the substitution of hydrogen by halogen atoms can increase drug binding specificity and the formed XB has played a role in the mutant stabilization process.187,188 Herein, in order to figure out the benefits of XB in biology-associated systems, a XB-based model complex was investigated which resembles the binding of base pairs. 2-Bromopyridine-3-carboxylic acid was initially chosen as the model compound since it has a Br substituent and an electron-rich oxygen that is expected to form a dimer structure via two Br-O halogen bonds. However, the published crystal structure189 (Figure B.1, the deposition number in The Cambridge Crystallographic Data Centre: 751725) overturned this hypothesis. It seems that the HB formed between the hydroxyl of the carboxylic group and the N in the pyridine core is dominant in the crystal structure compared to those debilitated Br-O halogen bonds. This can be attributed to the weak electrophilicity of the bromine atom. Positive charge can be introduced into this pyridine core to enhance the electrophilicity of Br, thus improve the strength of Br-O XB bonds. Therefore, 2-bromo-3-carboxy-1-methylpyridinium triflate (M2BrCP) was synthesized as shown in Figure B.2. It is expected to build up a dimer structure which is similar to the 171 complexation of base pairs. In addition, the carboxylic group can be tuned by the adjustment of pH. The deprotonation of the carboxylic group is anticipated to influence the strength of the Br-O halogen bonds, and further influence the molecular geometry. Figure B.1 Crystal structure of 2-bromopyridine-3-carboxylic acid. Figure B.2 Structure of 2-bromo-3-carboxy-1-methylpyridium triflate, dimer form, deprotonated dimer form, respectively. (From left to right) B.2 Results and Discussion The most straightforward way of unravelling the structure of M2BrCP is to obtain the XRD result. As shown in Figure B.3 (left), the dimer structure is formed as expected. The dimer structure was held together by two Br-O XBs with slightly different bond lengths (3.066 and 3.111 Å, the sum of the Van der Waals radius is 3.370 Å). Surprisingly, the two aromatic systems in the dimer structure are co-planar, but the oxygens in the carboxylic groups are out of that plane. Furthermore, 172 a minor disorder was observed of the carboxylic group as displayed in the Figure B.3 (right). In this minor disorder, the carboxylic group is more flattened and closer to the Br atom in the neighboring M2BrCP molecule (i.e., the counterpart in the dimer structure). It indicates that the XB might be dynamic in this system. Figure B.3 The dimer structure of M2BrCP (left), and the disorder structure in the XRD results (right). However, some unexpected features were discovered from the XRD results. (Another crystal was picked up in the same vial where the crystal in Figure B.4 has grown) In this crystal structure, the counterion was bromide rather than triflate. It suggested the possible decomposition in the M2BrCP sample. Some bromine atoms attached to the pyridinium core might be replaced by O from water in the solvent. Figure B.4 The unexpected features found in XRD data. In contrast, the deprotonated M2BrCP (de-M2BrCP) was prepared by mixing the M2BrCP with weak base (1:1 ratio). The crystal structure was also obtained using slow evaporation method. The 173 resolved crystal structure is unexpected as illustrated in Figure B.5. The bromine substituent is completely missing, while one O atom has replaced the previous Br. It seems that the hydrogen atom H2 is interchangeable between the two hydroxyl oxygen atoms O1 and O2. Compared with M2BrCP system, de-M2BrCP undergoes more severe hydrolysis during which the bromine atom was substituted by oxygen derived from the solvent. Figure B.5 The crystal structure of de-M2BrCP. B.3 Conclusion and Reflections Other techniques like NMR and XAS were also applied to investigate this system. The obtained results have all supported the finding from XRD -- M2BrCP could be synthesized but went through hydrolysis in the presence of water or other bases; The lifetime of de-M2BrCP is too short since M2BrCP would experience severe hydrolysis once the pH increases. It is intriguing that the methylation process enables the formation of DNA-like dimer structure due to the enhancement of XB strength (especially the electrophilicity of the Br). However, the instability of such compound has hindered the further investigation and application. A better molecular design and structural modification should be carried out in order to establish a more practical system. 174 Appendix C Supplementary Information of Chapter 2 C.1 Single Crystal X-Ray Diffraction Data Table C-1 Crystal data and structure refinement for DPEI-OTf. Identification code DPEI-OTf Empirical formula C13H8F3IO3S Formula weight 428.15 Temperature/K 173.0 Crystal system monoclinic Space group P21/c a/Å 7.3689(6) b/Å 16.3721(13) c/Å 11.3809(9) α/° 90 β/° 90.2930(10) γ/° 90 Volume/Å3 1373.02(19) Z 4 ρcalcg/cm3 2.071 μ/mm-1 2.525 F(000) 824.0 Crystal size/mm3 0.243 × 0.24 × 0.146 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.358 to 56.62 Index ranges -9 ≤ h ≤ 9, -21 ≤ k ≤ 21, -14 ≤ l ≤ 15 Reflections collected 15904 Independent reflections 3416 [Rint = 0.0226, Rsigma = 0.0182] Data/restraints/parameters 3416/0/190 Goodness-of-fit on F2 1.074 Final R indexes [I>=2σ (I)] R1 = 0.0171, wR2 = 0.0359 Final R indexes [all data] R1 = 0.0204, wR2 = 0.0370 Largest diff. peak/hole / e Å-3 0.45/-0.35 Table C-2 Crystal data and structure refinement for DPEI-Cl. Identification code DPEI-Cl Empirical formula C12H8ClI 175 Formula weight 314.53 Temperature/K 173.0 Crystal system monoclinic Space group C2/m a/Å 8.6868(14) b/Å 18.106(3) c/Å 7.0263(11) α/° 90 β/° 110.679(2) γ/° 90 Volume/Å3 1033.9(3) Z 4 ρcalcg/cm3 2.021 μ/mm-1 3.308 F(000) 600.0 Crystal size/mm3 0.347 × 0.227 × 0.19 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.5 to 56.588 Index ranges -11 ≤ h ≤ 11, -24 ≤ k ≤ 24, -9 ≤ l ≤ 9 Reflections collected 7878 Independent reflections 1334 [Rint = 0.0210, Rsigma = 0.0144] Data/restraints/parameters 1334/0/66 Goodness-of-fit on F2 1.280 Final R indexes [I>=2σ (I)] R1 = 0.0203, wR2 = 0.0456 Final R indexes [all data] R1 = 0.0229, wR2 = 0.0482 Largest diff. peak/hole / e Å-3 1.23/-1.09 Table C-3 Crystal data and structure refinement for DPEI-Br. Identification code DPEI-Br Empirical formula C12H8BrI Formula weight 358.99 Temperature/K 173.0 Crystal system monoclinic Space group C2/m a/Å 8.9017(19) b/Å 18.456(4) c/Å 7.0212(15) α/° 90 β/° 110.839(2) γ/° 90 176 Volume/Å3 1078.0(4) Z 4 ρcalcg/cm3 2.212 μ/mm-1 6.632 F(000) 672.0 Crystal size/mm3 0.522 × 0.294 × 0.204 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.414 to 56.626 Index ranges -11 ≤ h ≤ 11, -24 ≤ k ≤ 24, -9 ≤ l ≤ 9 Reflections collected 12808 Independent reflections 12808 [Rint = 0.0343, Rsigma = 0.0460] Data/restraints/parameters 12808/0/67 Goodness-of-fit on F2 1.060 Final R indexes [I>=2σ (I)] R1 = 0.0283, wR2 = 0.0686 Final R indexes [all data] R1 = 0.0357, wR2 = 0.0723 Largest diff. peak/hole / e Å-3 1.01/-0.80 Table C-4 Crystal data and structure refinement for DPEI-I. Identification code DPEI-I Empirical formula C12H8I2 Formula weight 405.98 Temperature/K 173.0 Crystal system triclinic Space group P-1 a/Å 7.7151(6) b/Å 8.7742(7) c/Å 9.5930(8) α/° 67.038(2) β/° 86.057(2) γ/° 71.022(2) Volume/Å3 564.17(8) Z 2 ρcalcg/cm3 2.390 μ/mm-1 5.531 F(000) 372.0 Crystal size/mm3 0.181 × 0.163 × 0.113 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.622 to 56.626 Index ranges -10 ≤ h ≤ 10, -11 ≤ k ≤ 11, -12 ≤ l ≤ 12 Reflections collected 22223 177 Independent reflections 22223 [Rint = 0.0371, Rsigma = 0.0506] Data/restraints/parameters 22223/0/129 Goodness-of-fit on F2 1.036 Final R indexes [I>=2σ (I)] R1 = 0.0362, wR2 = 0.0907 Final R indexes [all data] R1 = 0.0438, wR2 = 0.0966 Largest diff. peak/hole / e Å-3 0.85/-0.67 Table C-5 Crystal data and structure refinement for DPI-Cl. Identification code DPI-Cl Empirical formula C12H10ClI Formula weight 316.55 Temperature/K 173 Crystal system monoclinic Space group C2/c a/Å 20.885(3) b/Å 5.7094(9) c/Å 20.062(3) α/° 90 β/° 102.380(2) γ/° 90 Volume/Å3 2336.6(6) Z 8 ρcalcg/cm3 1.800 μ/mm-1 2.928 F(000) 1216.0 Crystal size/mm3 0.408 × 0.148 × 0.095 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 3.994 to 56.652 Index ranges -27 ≤ h ≤ 27, -7 ≤ k ≤ 7, -26 ≤ l ≤ 26 Reflections collected 17653 Independent reflections 2923 [Rint = 0.0210, Rsigma = 0.0137] Data/restraints/parameters 2923/650/189 Goodness-of-fit on F2 1.123 Final R indexes [I>=2σ (I)] R1 = 0.0179, wR2 = 0.0394 Final R indexes [all data] R1 = 0.0206, wR2 = 0.0405 Largest diff. peak/hole / e Å-3 0.43/-0.26 Table C-6 Crystal data and structure refinement for DPI-Br. Identification code DPI-Br 178 Empirical formula C12H10BrI Formula weight 361.01 Temperature/K 173.0 Crystal system monoclinic Space group C2/c a/Å 21.322(5) b/Å 5.8001(14) c/Å 19.747(7) α/° 90 β/° 101.167(9) γ/° 90 Volume/Å3 2395.8(12) Z 8 ρcalcg/cm3 2.002 μ/mm-1 5.969 F(000) 1360.0 Crystal size/mm3 0.487 × 0.153 × 0.062 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 3.894 to 56.62 Index ranges -28 ≤ h ≤ 28, -7 ≤ k ≤ 7, -26 ≤ l ≤ 25 Reflections collected 22421 Independent reflections 2987 [Rint = 0.0453, Rsigma = 0.0317] Data/restraints/parameters 2987/319/171 Goodness-of-fit on F2 1.022 Final R indexes [I>=2σ (I)] R1 = 0.0223, wR2 = 0.0472 Final R indexes [all data] R1 = 0.0306, wR2 = 0.0505 Largest diff. peak/hole / e Å-3 0.64/-0.58 Table C-7 Crystal data and structure refinement for DPI-I. Identification code DPI-I Empirical formula C12H10I2 Formula weight 408.00 Temperature/K 173.0 Crystal system monoclinic Space group C2/c a/Å 22.131(3) b/Å 5.8228(7) c/Å 20.231(3) α/° 90 β/° 100.878(2) 179 γ/° 90 Volume/Å3 2560.2(5) Z 8 ρcalcg/cm3 2.117 μ/mm-1 4.876 F(000) 1504.0 Crystal size/mm3 0.338 × 0.203 × 0.172 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 3.748 to 56.9 Index ranges -29 ≤ h ≤ 29, -7 ≤ k ≤ 7, -27 ≤ l ≤ 26 Reflections collected 17291 Independent reflections 3231 [Rint = 0.0232, Rsigma = 0.0160] Data/restraints/parameters 3231/529/159 Goodness-of-fit on F2 1.190 Final R indexes [I>=2σ (I)] R1 = 0.0188, wR2 = 0.0382 Final R indexes [all data] R1 = 0.0215, wR2 = 0.0392 Largest diff. peak/hole / e Å-3 0.54/-0.59 Table C-8 Crystal data and structure refinement for DPEBr-OTf. Identification code DPEBr-OTf Empirical formula C13H8BrF3O3S Formula weight 381.16 Temperature/K 173.0 Crystal system monoclinic Space group P21/c a/Å 7.2253(6) b/Å 16.2983(14) c/Å 11.3300(9) α/° 90 β/° 91.0230(10) γ/° 90 Volume/Å3 1334.01(19) Z 4 ρcalcg/cm3 1.898 μ/mm-1 3.280 F(000) 752.0 Crystal size/mm3 0.226 × 0.156 × 0.125 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.378 to 57.364 Index ranges -9 ≤ h ≤ 9, -22 ≤ k ≤ 22, -15 ≤ l ≤ 15 180 Reflections collected 21248 Independent reflections 3442 [Rint = 0.0333, Rsigma = 0.0233] Data/restraints/parameters 3442/0/191 Goodness-of-fit on F2 1.055 Final R indexes [I>=2σ (I)] R1 = 0.0223, wR2 = 0.0505 Final R indexes [all data] R1 = 0.0299, wR2 = 0.0530 Largest diff. peak/hole / e Å-3 0.42/-0.36 Table C-9 Crystal data and structure refinement for DPEBr-Cl. Identification code DPEBr-Cl Empirical formula C12H8BrCl Formula weight 267.54 Temperature/K 173.0 Crystal system monoclinic Space group P21/c a/Å 7.1023(7) b/Å 17.3752(16) c/Å 8.7256(8) α/° 90 β/° 111.6630(10) γ/° 90 Volume/Å3 1000.72(16) Z 4 ρcalcg/cm3 1.776 μ/mm-1 4.325 F(000) 528.0 Crystal size/mm3 0.278 × 0.176 × 0.044 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.688 to 56.594 Index ranges -9 ≤ h ≤ 9, -23 ≤ k ≤ 23, -11 ≤ l ≤ 11 Reflections collected 19498 Independent reflections 2481 [Rint = 0.0379, Rsigma = 0.0242] Data/restraints/parameters 2481/0/127 Goodness-of-fit on F2 1.095 Final R indexes [I>=2σ (I)] R1 = 0.0258, wR2 = 0.0567 Final R indexes [all data] R1 = 0.0380, wR2 = 0.0603 Largest diff. peak/hole / e Å-3 0.84/-0.51 Table C-10 Crystal data and structure refinement for DPEBr-Br. 181 Identification code DPEBr-Br Empirical formula C12H8Br2 Formula weight 312.00 Temperature/K 173.0 Crystal system triclinic Space group P-1 a/Å 6.9906(16) b/Å 8.858(2) c/Å 9.833(2) α/° 66.521(3) β/° 87.569(3) γ/° 69.037(2) Volume/Å3 518.0(2) Z 2 ρcalcg/cm3 2.000 μ/mm-1 7.778 F(000) 300.0 Crystal size/mm3 0.257 × 0.183 × 0.092 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.548 to 56.584 Index ranges -9 ≤ h ≤ 9, -11 ≤ k ≤ 11, -13 ≤ l ≤ 13 Reflections collected 2572 Independent reflections 2572 [Rint = 0.0361, Rsigma = 0.0454] Data/restraints/parameters 2572/0/127 Goodness-of-fit on F2 1.088 Final R indexes [I>=2σ (I)] R1 = 0.0404, wR2 = 0.0930 Final R indexes [all data] R1 = 0.0570, wR2 = 0.0963 Largest diff. peak/hole / e Å-3 1.56/-0.94 Table C-11 Crystal data and structure refinement for DPEBr-I. Identification code DPEBr-I Empirical formula C12H8BrI Formula weight 358.99 Temperature/K 173.0 Crystal system triclinic Space group P-1 a/Å 7.6034(3) b/Å 8.8503(3) c/Å 9.4481(3) α/° 65.7690(10) 182 β/° 85.0710(10) γ/° 69.7320(10) Volume/Å3 542.70(3) Z 2 ρcalcg/cm3 2.197 μ/mm-1 6.587 F(000) 336.0 Crystal size/mm3 0.269 × 0.09 × 0.039 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 4.738 to 60.066 Index ranges -10 ≤ h ≤ 10, -12 ≤ k ≤ 12, -13 ≤ l ≤ 13 Reflections collected 15923 Independent reflections 3173 [Rint = 0.0368, Rsigma = 0.0313] Data/restraints/parameters 3173/0/127 Goodness-of-fit on F2 1.030 Final R indexes [I>=2σ (I)] R1 = 0.0228, wR2 = 0.0405 Final R indexes [all data] R1 = 0.0345, wR2 = 0.0436 Largest diff. peak/hole / e Å-3 0.48/-0.53 C.2 13C NMR spectra Figure C.1 13C NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPI-X series. X = OTf, Cl, Br, IDPI-OTfDPI-ClDPI-BrDPI-I183 Figure C.2 13C NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEI-X series. Figure C.3 13C NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPEBr-X series. X = OTf, Cl, Br, IDPEI-OTfDPEI-ClDPEI-BrDPEI-IX = OTf, Cl, Br, IDPEBr-OTfDPEBr-ClDPEBr-BrDPEBr-I184 Figure C.4 13C NMR (400 MHz, 25°C, dimethyl sulfoxide-d6) spectra of DPECl-X series.
Thesis/Dissertation
eng
Chemistry
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Straus, Suzana
Kennepohl, Pierre
Defining the role of partially covalent weak interactions in chemical reactions
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