NMR structural determination of natural and organic molecules. Theory and applications of 1H and 13C NMR spectroscopy: chemical shift, coupling constants, relaxation, spectra of first order and higher order, chemical and magnetic equivalence. NMR and stereochemistry. APT, DEPT, inept. Effect Noe. 2D NMR (COSY, DQF-COSY, TOCSY, HETCOR, COLOC, INADEQUATE, HMBC, HSQC, H2BC, 2DNOESY, Roesy). Heteronuclea by NMR.
Book list is provided at the beginning of the course.
Learning Objectives
Acquire knowledge to determine the structure of organic molecules of medium complexity through the use of modern NMR spectroscopic techniques.
Prerequisites
Courses required: Organic Chemistry I and II
Courses recommended: none
Teaching Methods
Total number of hours for Lectures (hours): 48
Total number of hours for Laboratory-field practice : 35
Type of Assessment
Three written tests in itinere. Testing is not mandatory; in case of failure, there is a written preliminary examination and then the oral ine. Five annual sessions.
Course program
Significance of the structure elucidation. Molecular weight and empirical formula. Number of unsaturation. The contribution of different spectroscopic techniques. NMR spectroscopy: theoretical introduction. Principles of NMR experiment. The spectra in continuous wave and the pulse method. The magnetically active nuclea. The resonance condition. Magnets. Motion of the spins in the rotating frame. Vector representation of the pulse. Time and frequency domain. To sample the signal, the digital resolution and acquisition time, zero-filling, the "pattern" of the spectrum. The quadrature phase, the folding of signals: Nyquist Theorem. The relaxation. The spectral parameters: the chemical shift, the reference, the screen Nuclear. The coupling of spin exercises. Spectra of the first order and higher order. The concepts of chemical and magnetic equivalence. The spin systems. Examples. Classification, nomenclature and importance. Experimental considerations. Exercises-dimensional 1H-NMR spectroscopy: Influence of constant charge density on the screen. Lamb's theory. Effects of neighboring groups. Effects of magnetic anisotropy. McConnell's theory. Mesh currents. Karplus-Pople theory. Effect of electric fields. Intermolecular interactions. Bridge hydrogen bond and solvent effect. Isotope effects. The protons bound to heteroatoms. The rate of chemical exchange, the effects quadrupolari.Esercizi NMR and stereochemistry: Homotopy protons, and diastereotopici enantiotopic. Gutowski theory. Determination of enantiomeric excess. Examination of the chemical shifts in the major classes of organic compounds, aliphatic acyclic and cyclic, and aromatic eteroaromatici.Esempi The fine structure of 1H-NMR. Direct dipolar interaction theory and the theory of Fermi-Ramsey. Examination of the coupling constants. The reduced coupling constant gives the sign of the coupling constant. The geminal coupling (2J (H, H)): the angle dependence of binding, effect of substituents, diagnostic importance in olefinic systems. Vicinal coupling (3J (H, H)): dihedral angle dependence, effect of substituents, Karplus rule. Importance in systems sp2 and sp3. The H-H coupling in aromatic systems. The long-range coupling constants (allyl and omoalliliche). Years. The methods of simplification of the spectra of higher order: double resonance experiments (selective decoupling omonucleare), shift reagents. NMR routine and standard tests (line-shape, resolution and sensitivity). 13C-NMR spectroscopy-dimensional: The concept of receptivity, the importance of the pulse method. Factors affecting the intensity of the signals: the spin-lattice relaxation and spin-spin relaxation mechanisms for nuclei to spin 1 / 2, introducing nuclear Overhauser effect. The rotating reference system and the effect of pulses on longitudinal magnetization. The spin-echo and the experimental determination of the relaxation time T1, the T1 and the relationship between chemical structure. The width of the NMR signals. The chemical shift of carbon-13: importance of the paramagnetic term in the evaluation of the constant of the screen. The Karplus-Pople equation, and its amenability to organic terms. Examination of the chemical shifts of the main functional groups. Rules of thumb for determining the chemical shift.Esercizi The CH coupling constants: a pair bond (1J (CH)), hybridization dependence and effect of the substituents. Geminal coupling (2J (CH)), vicinal (3J (CH)) and long-range. C-H coupling in aromatic systems. Correlations between the pairs C-H and H-H. Spin decoupling 13C-NMR spectroscopy: The spectrum of 13C under full proton decoupling. Acquisition of the spectrum. Exercises The problem of the multiplicity of carbon atoms (groups CH, CH2 and CH3). The spectra in the off-resonance decoupling conditions, the method 'attached proton test' (APT). Exercises fully coupled 13C spectra the proton technique 'gated decoupling'. The selective heteronuclear decoupling. Methods of selective population inversion and polarization transfer (SPI and SPT). [2] The technique inept (inept inept and refocused): effects on sensitivity. The technique of choice (DEPT) for determining multiplicity '. Nuclear Overhauser Effect: Introduction and origin of the phenomenon. The system of two spins. The relaxation through dipolar coupling. The NOE distances and internucleari. The maximum NOE. Measurement techniques and experimental aspects. The difference method (1D-NOESY-spectra NOEDIFF). Quantitative determination. Examples of applications in homo-and two-dimensional NMR spectroscopy eteronucleare.Esercizi: The two-dimensional NMR experiment. The periods of preparation, evolution and mixing. Jeener's experiment. The magnetization transfer. The acquisition of data. The graphic representation. Two-dimensional J-resolved experiments hetero-(C, H) and homo-(H, H) nuclear. The heteronuclear correlation spectrum of CH (H, C-COSY or HETCOR), theory and practical applications. The long-range correlations Exercises (colocation). The exercises range correlation omonucleare H, H (H, H-COSY), theory and examples of interpretation, the COSY-90 and optimization for constant long-range (LR-COSY, COSY-45), the experiment phase-sensitive (PS-COSY). Exercises The selection phase coherence and consistency of the paths through the phase cycles. The double-quantum filtered COSY experiment (DQF-COSY). Carbon-Carbon Correlations: Inadequate two-dimensional experiment. Representation, feasibility. Exercises exchange spectroscopy: NOESY experiment. Techniques, CH inverse correlation: the reverse-Inept experiment. HMQC (Heteronuclear Multiple Quantum Coherence) and HSQC (Heteronuclear Single Quantum Coherence). The experiment TOCSY (HOHAHA). Brief use of magnetic field gradients (PFG) in modern NMR techniques.