Chemistry | Course catalogue

PHYSICAL METHODS IN ORGANIC CHEMISTRY WITH EXCERCISES

Course objectives

The main target of the course from a theoretical standpoint is to give students a deeper knowledge of the basical principles of NMR spectroscopy, integrated by updates about modern hardware and tecniques. Students will have to reach a good skill of detecting the spin systems inside a molecule, through the analysis of chemical and magnetic equivalence. The satisfactory level of knowledge will have to be extended also to all the spectroscopic tools and procedures aimed to clarify the molecular connectivity, the stereochemical and conformational analysis. At this purpose students will receive a good knowledge of bidimensional NMR spectroscopy and its applications in the field of molecular structural investigation. As regards the practical aspects of the knowledge acquired by students, they will learn how to analyze complex spin systems and to interpretate bidimensional NMR spectra. The theory given in the course will make students able to interpretate and even predict the appearance of one- and bidimensional spectra. The practical abilities in structure delucidation will be developed through exercises in class sessions, during which students will interpretate one- and bidimensional spectra of increasing complexity. In the same exercise sessions students will get familiar to predict and formulate the appearance of a spectrum of a given known molecule. The abilities of presenting notions and knowledge transfer regarding the content of the course will be developed and strenghtened by requiring the students during the class sessions to answer to theoretical questions related to course contents, focusing their attention on the importance of correct definitions and statements. Knowledge acquired in this course will make the students able to deal independently with NMR-related structural investigation during the rest of their educational pathway, and also in a likely post-graduation educational experience, like Ph.D.

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ANDREA D'ANNIBALE Lecturers' profile

Program - Frequency - Exams

Course program

Fundamentals of Fourier Transform NMR: nuclear magnetic moment, spin number: nuclei with I = ½ and quadrupolar nuclei. Macroscopic magnetiuzation, classical description of resonance phenomenon, rotating laboratory frame, relaxation. Excitation, pulse sequence, free induction decay (FID). Fourier transform, real and imaginary part of a spectrum, Zero- and first-order phase errors, phase correction. Hardware of NMR spectrometers, probe structure, analogic-to-digital converter. Acquisition and digitization of FID: Nyquist frequency, digital resolution, dwell time, acquisition time, spectral width. Apodization, FID truncation, exponential and gaussian window function, matched filter. Exercises of FID manipulation with MestreC software. The NMR experiment: spectrometer tuning, locking and shimming, field homogeneity optimization, matching. Sensitivity of NMR experiment: signal-to-noise ratio, thermal noise, methods to increase sensitivity through hardware: cryoprobe, microprobe. Line width and Heisenberg principle. Longitudinal (spin-lattice) and transverse (spin-spin) relaxation processes, times T1 and T2. Mechanisms of longitudinal relaxation: dipole-dipole interaction (DD), chemical shift anisotropy (CSA), spin-rotation (SR) and quadrupolar relaxation (Q). Correlation times c, and relationship between molecular motion, molecular structure and relaxation times. Inversion recovery sequence, measurement of T1. Chemical shift and molecular structure: diamagnetic shielding, diamagnetic anisotropy, electric field effects, inter- and intramolecular interactions, solvent effects on chemical shift. Anisotropic effects on NMR spectra and structure determinazion. Johnson Bovey plot. Chemical equivalence and molecular simmetry, Mislow classification of chemically equivalent nuclei. Spin-spin coupling: scalar coupling, order of a spectrum. Spin systems, Pople notation. First-order multiplets, interpretation by inverted splitting tree deconvolution method. Structural effects on the geminal and vicinal coupling constant magnitude. Karplus equation and its application to conformational and stereochemical problems. Long-range couplings: W-type couplings, allylic and propargylic couplings. Strong coupling and virtual coupling. Homonuclear decoupling. Nuclear Overhauser effect (NOE): perturbation of level populations, Solomons diagrams, relationship between NOE and dipole-dipole relaxation mechanism, spin diffusion and relay NOE. Homonuclear NOE, NOE difference spectra. Examples of application of NOE to structural, conformational and stereochemical determination. Lanthanide-induced shift reagents, contact and pseudocontact effects. Example of spectrum semplification by shift reagents. Other magnetically active nuclei: 31P e 19F spectral properties, chemical shifts and coupling constants to hydrogen and carbon. Quadrupolar nuclei and their spectral properties. Satellite peaks, and their applications to structure determination. 1H-NMR and stereochemistry: enantiomeric excess determination by chiral shift reagents. Chemical derivatization of chiral compounds and determination of absolute configuration by NMR: Mosher method. Dynamic NMR: investigation of dynamic processs. Exchange processes. Observing reaction by NMR. 13C-NMR: Relaxation of carbons. NOE and signal intensity. Chemical shifts of organic compound main classes. Calculation of chemical shift through empyrical correlation, equation of Grant and Paul. Gamma-effect, heavy atom effect. J- coupling of carbon with other important nuclides. Recovering informations: Gated- and Inverse Gated-decoupling. Complex pulse sequences, spin-echo and Attached Proton Test experiment. Recovering sensitivity: polarization transfer. Exercises of structure determination by 1H and 13C combined spectra. 2D NMR Fundamentals of a 2D experiment, structure orf a 2D pulse sequence, appearance of a 2D spectrum. Determining the coupling: J-resolved homo- and heteronuclear spectroscopy. Chemical shift correlation spectroscopy: the sequence of Jeener, homonuclear COSY experiment and its variants, heteronuclear HETCOR experiment. Exercises of 2D spectra interpretation. Inverse 2D spectroscopy: correlations through bonds at short and long range: HMQC, HSQC, HMBC and TOCSY experiments. Correlations through space: NOESY experiment. Diffusion NMR spectroscopy. DOSY exepriment.

Prerequisites

Students should have a satisfactory knowledge of the basic principles of monodimensional NMR (Basic principles, coupling, chemical shift). Essential requirement.

Books

To review NMR principles: Silverstein et al. "Spectrometric Identification of Organic Compounds",Eight edition, Wiley 2014 For course main contents: Friebolin "One and Two-Dimensional NMR Spectrocopy", Fifth Edition, Wiley VCH 2010. Claridge "High-resolution NMR Tecniques in Organic Chemistry", Second Edition, Elsevier 2009. Gunther "NMR Spectroscopy", Third Edition, Wiley 2013. For the interpretation of 2D spectra: Field, Li, Magill "Organic Structures from 2D NMR spectra", Wiley 2015. Randazzo "Guida Pratica all'Interpretazione di Spettri NMR", Loghia 2018.

Teaching mode

2 h Frontal teaching with a 15 min break.

Frequency

Course attendance is strongly suggested to students, even if not mandatory.

Exam mode

Written test about knowledge of the main NMR spectral features of a given molecule. Oral test of 40 minutes duration.

Lesson mode

The course will be held through classroom-taught lessons. Exercise will be solved in classroom.