Catalogo dei Corsi di studio

General expected learning outcomes
The course of Physical Methods in Organic Chemistry aims to provide students with the fundamental knowledge of modern chromatographic and spectroscopic techniques, commonly used in the study of organic molecules in research and control laboratories. The course also aims to provide the ability to identify the most suitable chromatographic techniques for solving real problems, and to understand UV, IR, MS and NMR spectra of organic molecules. At the end of the course the student will acquire the skills to analyze in-depth NMR, IR and MS spectra, to derive from their combined analysis the structure of unknown compounds, and to predict the spectroscopic properties of new compounds.

Specific expected learning outcomes
1. Knowledge and understanding
Students successfully completing this course understand and master the fundamentals of modern chromatographic techniques: adsorption, partition, kinetic aspects, van Deemter equation, composition and morphology of stationary phases, simple structure-retention relationships, solute-stationary phase-mobile phase interactions. The students know and understand the fundamentals of spectroscopic techniques: interaction between matter and electromagnetic radiation. Electromagnetic spectrum, wavelength, frequency, energy content, intensity of radiation, absorption, emission, scattering, excited states, quantization. The students know and understand the theoretical principles and practical applications of IR spectroscopy (harmonic and anharmonic oscillators, fundamental vibrations, overtone, combination bands, characteristic absorptions of the main functional groups), 1H-NMR and 13C-NMR (nuclei in a magnetic field, resonance, relaxation processes, shielding and shielding constants, homo- and hetero-nuclear spin-coupling, Pople's spin notation systems, Karplus relation) and MS (ionization and fragmentation processes, analyzers). The students know and understand the theoretical principles and practical applications of instrumental hyphenated techniques (LC-MS). The students are able to understand how the spectral parameters can be influenced by the experimental conditions (physical state of the sample, concentration, solvent, temperature).

2. Applying knowledge and understanding
Students successfully completing this course should be able to select the most suitable chromatographic technique according to the structure of the compounds to be analyzed and is able to describe the process underlying the choice of stationary phases, mobile phases and detectors. The student is able to control and optimize the kinetic and thermodynamic parameters of the chromatographic process and is able to apply the acquired knowledge to new problems typical of research or working contexts. The student is able to interpret IR, NMR, MS spectra of simple pure organic compounds, and is able to choose the spectroscopic technique or the combination of several techniques suitable for diverse structural investigations (control of the conversion of functional groups, identification of impurities, ). The student is able to apply the known instrumental techniques to new problems that may arise in research or work areas.

3. Making judgements
Students successfully completing this course should be able to integrate the knowledge acquired during the course with those of the physical-organic chemistry that characterizes the Degree Course in CTF (study of equilibrium, reaction speed, reaction mechanisms, study of intermediates, selectivity, stereochemistry ). The student will be able to acquire data from databases and interpret multispectral data useful for solving typical problems in research and production areas such as synthesis laboratories, quality control of active ingredients, laboratories for the analysis of products of natural origin, complex mixtures of metabolites. These skills are stimulated and developed typically during exercises of interpretation of spectra, during lectures and exercises

4. Communication skills
Students successfully completing this course will be able to communicate what has been learned in a clear and rigorous manner, both to non-expert interlocutors and to experts in the field. The student is stimulated to interpersonal communication typically during classroom exercises.

5. Learning skills
Students successfully completing this course should have developed autonomous learning abilities related to chromatographic and spectroscopic techniques through the consultation of databases, bibliographic material and scientific literature available on-line.

Programme

High-performance chromatographic techniques.
Theory and principles. Main application fields of chromatography. High Performance Liquid Chromatography (HPLC). General aspects. Chromatographic parameters (capacity factors, selectivity, efficiency, resolution). Van Deemter equation. Chromatographic supports and their physico-chemical properties: surface chemistry, specific surface area, pore size and volume. Bonded-phases: chemistry and stability. Separation mechanisms: liquid-liquid, liquid-solid, normal-phase (NP), reversed-phase (RP). Ion-Exchange Chromatography (IEC). Paired-Ion Chromatography (PIC). Size-Exclusion Chromatography (SEC). Hydrophobic-Interaction Chromatography (HIC), Hydrophilic interaction Chromatography (HILIC). Elution mode: isocratic and gradient. Detectors.
High-Resolution Gas Chromatography (HRGC). General aspects. Microbore and packed microcapillary columns. Detectors. Mass spectrometry interface (GC-MS)
Stereoselective and enantioselective separations. Direct and indirect approach. Main interactions between selector and selectands. Thermodynamics of enantiomers separation. Chiral stationary phases (CSPs) for HPLC and HRGC.

Infrared Spectroscopy (IR)
General aspects. Theory of Infrared Spectroscopy (IR). Main functional groups and typical IR absorptions of organic molecules. Basics of Fourier Tranform IR (FT-IR) spectrum interpretation. Identification and structure elucidation of organic molecules by interpretation of FT-IR spectra.
Ultraviolet Spectroscopy (UV)
General aspects. Theory of Ultraviolet Spectroscopy (UV). Lambert-Beer law. Electronic transitions →*, n→*, n→*, →*. UV instrumentation and solvents. Typical UV absorbing of compounds featuring only bonds, of aliphatic compounds with n electrons and of compounds with electrons. Aromatic systems.
Nuclear Magnetic Resonance (NMR)
General aspects. Theory of Nuclear Magnetic Resonance (NMR). Nuclear magnetic moment, spin number, angular momentum, magnetogyric ratio. Larmor precession. Proton Magnetic Resonance Spectrometry (1H-NMR). Important concepts and parameters in NMR. Instrumentation and sample handling. Chemical shift (diamagnetic anisotropy, bond anisotropic effect, ring-current effect, hydrogen bond, solvent polarity and magnetic anisotropy). Spin-spin coupling, multiplets, spin systems. Protons on heteroatoms. Exchangeable protons. Coupling of protons to other important nuclei. Chemical shift equivalence. Magnetic equivalence (spin-coupling equivalence). AMX, ABX, and ABC rigid systems with three coupling constants. Chirality. Vicinal and geminal coupling in rigid systems: Karplus correlations. Long-range coupling. Selective spin decoupling. Double resonance. Nuclear Overhauser Effect (NOE). Shift reagents. Carbon Magnetic Resonance Spectrometry (13C-NMR). Total spin decoupling spectra. Off-resonance spectra. Chemical shift equivalence. Correlation NMR spectrometry. DEPT and APT experiments. Variable temperature NMR. Basics of 1H-NMR and 13C-NMR spectrum interpretation.
Mass Spectrometry (MS)
Ionization systems: electron impact, chemical ionization, fast atom bombardment (FAB) – ESI – APCi – MALDI.
Analyzers: magnetic and electrostatic sectors, quadrupolar systems, ion trap, time of flight systems, orbitrap, tandem mass spectrometry.
Molecular ion, exact masses, isotopic abundance, isotopic clusters, elemental composition.
Typical fragmentation patterns in mass spectra, McLafferty rearrangement.

Adopted texts

Suggested reading: Silverstein, Webster, Kiemle. Identificazione spettrometrica di composti organici, Terza Edizione Italiana (2016) Casa Editrice Ambrosiana, Milano.