Learning objectives
The first part of the course is aimed to give the participants a thorough knowledge of the advanced tools for the structural analysis or organic compounds through monodimensional and bidimensional NMR spectroscopy. The basic principles of the bibliographic research with a particular reference to the organic chemistry resources (software and library tools) will be also tackled. The acquisition of advanced techniques for the synthesis and purification of organic compounds is obtained through an extensive laboratory practice in the second part of the course. The compounds synthesized will be purified with chromatographic techniques and structurally characterized with spectroscopic techniques (MS, UV, IR, 1H and 13C NMR).
Course unit content
Magnetic properties of nuclei: angular momentum and spin angular momentum. NMR Frequencies and Chemical shift. Energy levels and NMR spectra. The Vector model. Fundamental concepts of 2D NMR spectroscopy. Relaxation and Nuclear Overhauser Effect (NOE). The modern NMR spectrometer. Interpretation of 1D e 2D NMR spectra and determination of the structure of an organic compound. Organic Chemistry Resources: databases, software clients and library tools to carry out a bibliographic research for the synthesis of an organic compound. Multistep synthesis, purification and spectroscopic characterization of an known organic compound.
Full programme
Magnetic properties of nuclei: angular momentum and spin angular momentum. Microscopic magnetism. Correlation between magnetism and spin angular momentum.
- NMR Frequencies and Chemical shift. Linewidth and lineshape. Scalar coupling. The basic NMR experiment.
- Energy levels and NMR spectra. The spectrum for one spin. The energy levels for two coupled spins.
- The Vector model. The bulk magnetization. Larmor precession. Detection. Pulses. "On resonance" pulses. The rotating frame. The basic impulse-acquisition sequence. Calibration of pulses. The Spin-Echo experiment. Pulses of various phase. "Off-resonance" effetcs and "soft" pulses. Fourier Transformation and data processing. FID representation. Peaks linewidth and lineshape. FID manipulation. Zero filling.
- The "Product Operators" formalism. Product operators for one spin. Hamiltonians for spins and delays. Equation of motion. The spin-echo experiments with the product operators formalism. Product operators for two weakly coupled spins.
- Fundamental concepts of 2D NMR spectroscopy. 2D NMR experiments with coherence transfer mediated by J-coupling. COSY and DQF-COSY: pulses sequence and spectra interpretation. Double Quantum NMR Spectroscopy. Heterocorrelated 2D NMR spectroscopy. HMQC, HSQC and HMBC experiments: pulses sequence and spectra interpretation. 2D TOCSY NMR experiment: pulses sequence and spectra interpretation.
- Relaxation and Nuclear Overhauser Effect (NOE). The origin of the nuclear relaxation phenomenon. Mechanisms of relaxation. Correlation time. Population of the states. Longitudinal relaxation of isolated spins. Dipolar longitudinal relaxation of two spins. Cross-relaxation. Relaxation due to chemical shift anisotropy.
- NOEDif, NOESY and ROESY experiments: pulses sequence and spectra interpretation
- Coherence selection: phase cycling cycle and field gradient pulses. Order of coherence. Coherence transfer pathways. Frequency discrimination and peak shape.
- The modern NMR spectrometer. Magnet and Probe, Lock Channel, Shim and homogeneity of the magnetic field. RF synthesizer, amplifier and duplexer. Receiver and Quadrature detection. Analogue to digital convertor (ADC). Limits of digitization.
- Organic Chemistry Resources: databases, software clients (SciFinder and Reaxys) and library tools to carry out a bibliographic research for the synthesis of an organic compound.
- Biblographic research, multistep synthesis and spectroscopic characterization of an known organic compound. 1D NMR spectra acquisition (1H and 13C).
Bibliography
Suggested Readings:
- M. Hesse, H. Meier, B. Zeeh, "Metodi spettroscopici in chimica Organica", 2^ edizione, EdiSES, 2010.
- R. M. Silverstein, F. X. Webster, D. J. Kiemle, “Identificazione spettrometrica di composti organici, 2^ edizione, Casa Editrice Ambrosiana (MI), 2006.
- D. H. Williams, I. Fleming, "Spectroscopic Methods in Organic Chemistry" 5th Edition, McGraw-Hill, 1996.
- T. D. W. Claridge "High-Resolution NMR Techniques in Organic Chemistry, 2nd edition, Tetrahedron Organic Chemistry, Vol. 27, Elsevier, Amsterdam, 2009.
- N. E. Jacobsen "NMR Spectroscopy Explained: Simplified Theory, Applications and Examples for Organic Chemistry and Structural Biology, Wiley, 2007.
Organic Lab Training:
- M. D'Ischia, "La Chimica Organica in Laboratorio", Piccin (PD), 2002.
- J. R. Mohrig et al. "Techniques in Organic Chemistry", 2nd ed., W.H. Freeman and Company, NY, 2006.
- J. Leonard et al. "Advanced Practical Organic Chemistry", 2nd edition, Stanley Thornes (Publisher) Ltd, UK, 1998.
Teaching methods
In the first part the course will be based on front lessons and class exercises, while in the second part a practical training will be taken in the Organic Synthesis Lab.
Assessment methods and criteria
Oral exam and written exercises.
