Structure Elucidation in Organic Chemistry -- Contents -- Preface -- List of Contributors -- Chapter 1 Interaction of Radiation with Matter -- 1.1 Introduction -- 1.2 Spectroscopy: A Definition -- 1.3 Electromagnetic Radiation -- 1.4 Electromagnetic Spectrum -- 1.5 Interaction of Radiation with Matter -- 1.6 Magnetic Spectroscopies -- 1.7 Pulse Techniques in NMR Spectroscopy -- 1.8 Line Widths -- 1.9 Selection Rules -- 1.10 Summary of Spectroscopic Techniques -- 1.10.1 Absorption-Based Methods -- 1.10.2 Emission-Based Methods -- 1.10.3 Scattering and Diffraction Methods -- References -- Chapter 2 Computational Spectroscopy Tools for Molecular Structure Analysis -- 2.1 Introduction -- 2.2 Potential Energy Surface and Molecular Structure -- 2.2.1 Minima and Conformational Analysis -- 2.2.2 Spectroscopic Tools for Structure Determination -- 2.3 Computational Aspects for Spectroscopic Techniques -- 2.3.1 DFT and Hybrid Approaches for Spectroscopic Applications -- 2.3.2 Rotational Spectroscopy -- 2.3.3 Vibrational Spectroscopy: Infrared (IR), Vibrational Circular Dichroism (VCD), Raman -- 2.3.4 Electronic Spectroscopy: One-Photon Absorption (OPA) and Electronic Circular Dichroism (ECD) -- 2.3.5 Magnetic Resonance Spectroscopy: Electronic Spin Resonance (ESR) -- 2.4 Application and Case Studies -- 2.4.1 Semi-Experimental Equilibrium Structure -- 2.4.2 Identification of Conformers/Tautomers -- 2.4.2.1 Rotational Spectrum of Proteinogenic Glutamic Acid -- 2.4.2.2 IR Spectrum of Glycine -- 2.4.2.3 Vibrational (IR/VCD) and Electronic (OPA/ECD) Spectra of (Z)-8-Methoxy-4-Cyclooctenone -- 2.4.2.4 ESR Spectra of Uracil Anion -- 2.4.3 3D Structure: Molecular Complexes and Flexible Macromolecules -- 2.4.3.1 Molecular Structure of Anisole Complexes -- 2.4.3.2 ESR Spectrum of Peptides -- Acknowledgments -- References.

Chapter 3 Absolute Configuration and Conformational Analysis of Chiral Compounds via Experimental and Theoretical Prediction of Chiroptical Properties: ORD, ECD, and VCD -- 3.1 Introduction -- 3.2 Chirality -- 3.3 What is a Chiroptical Method? -- 3.4 Quantum Mechanical (Ab Initio) Methods for Predicting Chiroptical Properties -- 3.5 Electronic Circular Dichroism (ECD) -- 3.5.1 Advantages of ECD -- 3.5.2 Limitations of ECD -- 3.5.3 Applications of ECD -- 3.5.3.1 Empirical Methods -- 3.5.3.2 Exciton Coupling -- 3.5.3.3 ECD Simulation via Ab Initio Methods: Conformational Analysis and Determination of AC -- 3.5.4 Challenge due to Vibronic Coupling -- 3.6 Vibrational Circular Dichroism (VCD) -- 3.6.1 Advantages of VCD -- 3.6.2 Limitations of VCD -- 3.6.3 Application of VCD -- 3.6.3.1 AC Assignment of Moderately Flexible Molecules with One Chiral Center -- 3.6.3.2 AC Assignment of Flexible Molecules with More Than One Chiral Center -- 3.6.3.3 Establishing Solute-Solvent and Solute-Solute Intermolecular Interactions of Chiral Molecules -- 3.6.3.4 AC Assignment via VCD Exciton Coupling Methodology-The Future Perspective -- 3.7 Optical Rotatory Dispersion (ORD) -- 3.7.1 Advantages of ORD -- 3.7.2 Limitations of ORD -- 3.8 When More than One Method is Needed -- 3.8.1 Combination of ECD and VCD -- 3.8.2 Combination of ECD and ORD -- 3.8.3 Combination of VCD and ORD -- 3.9 Concluding Remarks -- References -- Chapter 4 Mass Spectrometry Strategies in the Assignment of Molecular Structure: Breaking Chemical Bonds before Bringing the Pieces of the Puzzle Together -- 4.1 Introduction -- 4.2 Instrumentation and Technology -- 4.2.1 Ionization Techniques -- 4.2.2 Mass Analyzers -- 4.2.3 Tandem Mass Spectrometry Technologies -- 4.2.4 Data Acquisition Strategies in Tandem Mass Spectrometry.

4.3 Breaking Chemical Bonds-Fragmentation Reactions -- 4.3.1 Fragmentation of Odd-Electron Ions -- 4.3.2 Fragmentation of Even-Electron Ions -- 4.3.3 Additional Strategies and Tools -- 4.4 Confirmation of Identity -- 4.4.1 Retrieving Compound Identity by Library Searching -- 4.4.2 Multiple SRM Transitions in Residue Screening -- 4.4.3 Confirming the Identity of Synthetic Products -- 4.5 Putting the Puzzle Together-Structure Elucidation of Unknowns -- 4.5.1 Strategies for Identification of Related Substances -- 4.5.2 Identification of Unknowns -- 4.6 Conclusions and Perspectives -- Abbreviations -- References -- Chapter 5 Basic Principles of IR/Raman: Applications in Small Molecules Structural Elucidation -- 5.1 Introduction -- 5.2 Characteristic Vibrational Modes: Diatomics and Chemical Bonds -- 5.2.1 The Diatomic Example -- 5.2.2 Equilibrium Properties: Dipole Moment and Polarizability -- 5.3 Fundamental Vibrational Modes and Molecular Structure -- 5.4 Selection Rules and Finding the Number of Normal Modes in Each Symmetry Species -- 5.5 The Vibrational Assignment of Raman and Infrared Spectra -- 5.6 Conclusions -- References -- Chapter 6 Solid-State NMR Applications in the Structural Elucidation of Small Molecules -- 6.1 Introduction -- 6.2 Line-Narrowing and Sensitivity Enhancement Methods in ssNMR Spectroscopy -- 6.3 Probing Dynamics in Solids -- 6.4 Application of ssNMR Spectroscopy to Small Molecules -- 6.4.1 Hydrogen Bonding -- 6.4.2 Guest Molecules Adsorbed in Porous Materials -- 6.4.2.1 Probe Molecules to Study the Acidity of Catalysts -- 6.4.2.2 Other Molecules Anchored on Materials -- 6.4.2.3 The Special Case of CO2 -- 6.4.3 Energy-Related Compounds -- 6.4.4 Pharmaceuticals -- 6.4.5 Biomolecules -- 6.5 NMR of Molecules on Surfaces (DNP) -- 6.6 NMR Crystallography -- Acronyms -- References.

Chapter 7 Simplified NMR Procedures for the Assignment of the Absolute Configuration -- 7.1 Introduction -- 7.2 Single Derivatization Methods for Mono- and Polyfunctional Compounds -- 7.2.1 Low Temperature -- 7.2.2 Selective Complexation -- 7.2.3 Esterification Shifts -- 7.3 Resin-Bound Chiral Derivatizing Agents (Mix and Shake Method) -- 7.4 Non-resin in Tube Assignment (BPG and BINOL Borates) -- 7.5 Tandem HPLC-NMR: Simultaneous Enantioresolution and Configurational Assignment -- 7.6 Assignment Based on the Chemical Shifts from the Auxiliaries -- 7.7 Scope and Conclusions -- References -- Chapter 8 Structural Elucidation of Small Organic Molecules Assisted by NMR in Aligned Media -- 8.1 Introduction -- 8.2 Aligning Media -- 8.2.1 Magnetic Susceptibility -- 8.2.2 Paramagnetic Systems -- 8.2.3 Mechanically Strained Polymer Gels -- 8.2.3.1 Strained Gels for Polar Solvents -- 8.3 Measurement of RDCs -- 8.3.1 Measurement of 1DCH RDCs -- 8.3.1.1 13C Detected Experiments -- 8.3.1.2 1H Detected Experiments -- 8.3.2 1H-1H Couplings E.COSY and P.E.HSQC Experiments -- 8.4 Computational Methodology -- 8.4.1 Determination of the Alignment Tensor -- 8.4.2 Symmetrical Rotors -- 8.5 Data Analysis: Use of RDCs as Structural Constraints in Small Molecules -- 8.5.1 Determination of Configuration for Rigid Molecules -- 8.5.2 Assignment of Diastereotopic Groups -- 8.5.3 RC Assignment in Molecules with Conformational Flexibility -- 8.5.3.1 Multitensor Approaches to the Flexibility Problem -- 8.5.3.2 Multiple-Tensors Analysis: Dimers and Pseudo-Dimers -- 8.6 RDCs and Determination of Absolute Configuration -- 8.6.1 Assignment of the Absolute Configuration: Combination of Residual Dipolar Couplings and Chiroptical Techniques -- 8.7 Conclusions and Perspectives -- Acknowledgments -- References.

Chapter 9 NMR Techniques for the Study of Transient Intermolecular Interactions -- 9.1 Introduction -- 9.2 Nuclear Overhauser Effect -- 9.2.1 Introduction to NOE-Based Methods -- 9.2.2 Transferred NOE -- 9.2.3 CORCEMA: Relaxation Matrix -- 9.2.4 Transfer-NOE Applications -- 9.2.5 Transfer-NOE: Quantitative Applications -- 9.3 Saturation Transfer Difference NMR -- 9.3.1 STD NMR Applications -- 9.3.1.1 Ligand Screening -- 9.3.1.2 Epitope Mapping -- 9.3.1.3 Quantitative Structural Analysis: CORCEMA-ST -- 9.3.1.4 Binding Constants from STD NMR -- 9.4 Diffusion NMR -- 9.4.1 Diffusion and Molecular Structure -- 9.4.2 Measuring Diffusion with NMR -- 9.4.3 Diffusion Coefficient in the Presence of Chemical Exchange -- 9.4.4 Diffusion NMR Applications -- 9.4.4.1 Diffusion NMR Screening -- 9.4.4.2 Diffusion NMR in the Study of Non-covalent Transient Intermolecular Interactions -- 9.4.4.3 Diffusion NMR in the Study of Self-aggregation -- 9.4.4.4 Diffusion NMR to Determine the Equilibrium Binding Constant -- 9.5 Conclusions -- References -- Chapter 10 Analysis of Molecular Interactions by Surface Plasmon Resonance Spectroscopy -- 10.1 Introduction -- 10.2 General Aspects of the Surface Plasmon Resonance Principle -- 10.3 The SPR Experiment -- 10.3.1 Sensor Surface Design and Preparation -- 10.3.1.1 Covalent Immobilization -- 10.3.1.2 Non-covalent Immobilization -- 10.3.2 The Binding Experiment -- 10.4 The Information Contained in the SPR Experiment -- 10.4.1 Qualitative Information -- 10.4.2 Binding Affinity and Kinetics -- 10.4.3 Concentration Analysis -- 10.4.4 Thermodynamics -- 10.5 SPR Applications: From Large to Small Molecules -- 10.5.1 Working with SPR and Large Molecules -- 10.5.1.1 Protein-Protein/Peptide Interactions -- 10.5.1.2 Antibody-Antigen Interactions -- 10.5.1.3 Oligonucleotides -- 10.5.1.4 Larger Structures.

10.5.2 Working with SPR and Small Molecules.