AIMS AND LEARNING OUTCOMES

This course continues and deepens the discussion of spectroscopic techniques (especially NMR, IR and MS) already discussed in the course of Organic Chemistry 2 of Bachelor Degree.

This course provides a more in-depth theoretical framework and further develops the range of practical applications aimed at determining the molecular structure of organic compounds, included the configurational and conformational aspects.

Particular emphasis is given to data analysis and the strategy for their interpretation, including the discussion about the practical solution of numerous real problems.

It is essential that the student has assimilated the notions taught in the course of Organic Chemistry 2, since only having aquired an adequate knowing of the fundamental aspects of this matter makes sense to deal with the study of the more advanced topics presented in this course.

TEACHING METHODS

6 ECTS of lectures (Descriptive slides are provided to students before classes through AulaWeb). Attendance is optional.

2 ECTS of classroom exercises and instrumental laboratory (the students are provided with slides about methods of approach to the solution of problems and with many problems, some addressed in classroom, others available for autonomous solution). Attendance is mandatory.

SYLLABUS/CONTENT

First module

1. Overview of spectroscopic methods: (i) the equilibrium distribution of molecules among the allowed energy levels, (ii) not-radiative transitions, (iii) electromagnetic radiations as perturbations of the equilibrium distribution, (iv) various kinds of molecular spectroscopy, their relative sensitivity and interaction times.
2. Basic principles of NMR spectroscopy: (i) the need of a strong static magnetic field B0 and an oscillating magnetic field in the rf range (ii) the inherent low sensitivity of this kind of spectroscopy, (iii) the magnetic dipole moment of a proton, an electron, a neutron and a nucleus in the general case; (iii) the resonance frequency as a function of B0, of the magnetogyric ratio and of the shielding factor: separation of the frequency ranges of the various isotopes and the need of the δ scale for the chemical shift; (iv) the bulk magnetic vector, the magnetic induction, the longitudinal and transverse relaxation; (v) intensity, stability and homogeneity requirements for B0: use of criomagnets, lock signal, shim currents, sample spinning; (vi) CW and FT spectrometers; input parameters to obtain FT spectra.
3. 1H NMR spectroscopy: (i) solvent residual signal, moisture signal; (ii) chemical equivalence from symmetry or from rapid position exchange; omotopic, enantiotopic and diastereotopic nuclei, (iii) integration of signal; (iv) chemical shifts as arising from neighbor electron circulations, local electron density and hydrogen bonds; (v) spin-spin splitting patterns and coupling constants; (vi) the Karplus equation and its applications; (vii) second-order spectrum from magnetic non-equivalence and from low Δν/J values; (viii) reduction of second-order spectra by larger B0 or the addition of shift reagents; (ix) coupling with 2H, 19F and 31P; (x) decoupling by natural rapid spin exchange, irradiation or chemical exchange, (xi) the nuclear Overhauser effect.
4. 13C NMR spectroscopy: (i) spectra in noise decoupling: solvent signal, chemical equivalence of carbons, lower intensity of the signals of quaternary carbons, discussion of the map of chemical shifts, couplings with 2H, 19F and 31P; (ii) Proton-coupled spectra: 1J(C,H), 2J(C,H), 3J(C,H); (iii) off-resonance and DEPT techniques.
5. Bidimensional NMR techniques: (i) general introduction, (ii) stacked and contour plots, (iii) J-resolved spectra, (iv) 1H-1H COSY, (v) NOESY, (vi) 1H-13C traditional Hetcor and HMQC, (vii) COLOC and HMBC, (viii) TOCSY
6. Other applications of NMR spectroscopy: configurational and conformational analysis (low temperature, shift reagents, nematic solvents), biomedical investigations (biologic fluids, Topic NMR, Imaging), origin of food (from isotopic ratios), cultural heritage.

Second module:

1. Mass spectrometry. A brief review of the theory. Fragmentation pathways related to the most common classes of organic compounds, mainly aimed at their identification.
2. Infrared spectroscopy. Reminders of the fundamental theoretical concepts. Interpreting IR spectra of the main classes of organic compounds. The practical uses of the technique will be discussed.
3. UV-Vis Spectroscopy. Short review to the basic theoretical knowledge. Relationships between structure of the organic molecules and their electronic spectra. Chromophores and auxochromes. The Woodward-Fieser rules. Applications of UV-Vis spectroscopy to structure determination and its uses in quantitative analysis.
4. Fluorescence spectroscopy. Mechanism of photoluminescence, singlet and triplet states, fluorescence spectra, instrumentation. Photoluminescence methods in analysis: direct methods, derivatization methods, quenching methods; an outline to applications in biology.

Practical lessons:

1. Several exercises requiring the identification of unknowns substances by means of the analysis of appropriate spectra with their interactive group discussion

2. Running NMR spectra of some organic molecules with different techniques and discuss them.

3. Application of the most common post-acquisition processing techniques of NMR spectroscopy.

RECOMMENDED READING/BIBLIOGRAPHY

• L. D. FIELD, S. STERNHELL, J. R. KALMAN, Organic Structures From Spectra (Wiley, 2013)
• P. CREWS, J. RODRIGUEZ, M. JASPARS, Organic Structure Analysis (Oxford University Press, 2010)
• J. B. LAMBERT, S. GRONERT, H. S. SHURVELL, D. A. LIGHTNER, R. G. COOKS, Organic Structural Spectroscopy (Prentice-Hall, 2010)
• D. H. WILLIAMS, I. FLEMING, Spectroscopic Methods in Organic Chemistry (McGraw-Hill, 2007)
• E. PRETSCH, P. BUHLMANN, M. BADERTSCHER, Structure Determination of Organic Compounds: Tables of Spectral Data (Springer, 2008)
• S. A. RICHARDS, J. C. HOLLERTON, Essential Practical NMR for Organic Chemistry (Wiley, 2011)
• J. KEELER, Understanding NMR Spectroscopy (Wiley, 2005)
• J. B. LAMBERT, E. P. MAZZOLA, Nuclear Magnetic Resonance Spectroscopy: An Introduction to Principles, Applications, and Experimental Methods (Prentice Hall College, 2003)
• R. S. MACOMBER, A Complete Introduction to Modern NMR Spectroscopy (Wiley, 1998)