C9536 - CARATTERIZZAZIONE STRUTTURALE DI MOLECOLE ORGANICHE NATURALI CON ESERCITAZIONI

Learning outcomes

At the end of the course, students will have acquired the theoretical and practical knowledge needed to identify and characterize an organic substance using the main spectroscopic and instrumental techniques employed in chemical and pharmaceutical laboratories. In particular, they will be able to: 1) interpret the fundamental spectroscopic data (UV-Vis, IR, NMR, mass spectrometry) associated with a substance; 2) evaluate and analyze the most appropriate experiments for each technique in order to draw structural conclusions; 3) make a reasoned selection of the most suitable analytical methodologies to solve specific problems of identification, purity, or molecular structure.

Course contents

Fundamental Concepts

Principle of energy quantization in atomic and molecular systems. Properties of electromagnetic radiation. Nature of excited states. Jablonski diagram.

Main relaxation mechanisms of excited states. Selection rules for transitions between different energy levels.

UV and Visible Spectroscopy

The Lambert-Beer law. Classification of electronic transitions based on the Molecular Orbital method. Instrumentation. Chromophores: polyenes, aromatic rings, carbonyl groups. Effects of substituents and solvents on electronic transitions. Structural information obtainable from an electronic spectrum. Coupling with chromatographic systems.

Interpretation of a UV-Vis spectrum.

Brief overview of polarimetry and circular dichroism of optically active substances.

Infrared Spectroscopy

Harmonic oscillator model. Selection rules for vibrational transitions. Level populations and intensity of spectral lines. Instrumentation. Rotational fine structure. Skeletal frequencies and group frequencies. Fingerprint region. Recognition of functional groups.

Interpretation of an IR spectrum.

Mass Spectrometry

Review of the general principles: ionization methods, ion separation, ion detection. Determination of exact mass. Measurement of high masses.

Molecular ion. Isotopic composition of a molecule. Main fragmentation reactions of organic molecules: beta-cleavage, benzylic and allylic cleavage, cleavage of non-activated bonds, McLafferty rearrangement, CO elimination.

Interpretation of an electron impact mass spectrum.

Nuclear Magnetic Resonance Spectroscopy (NMR)

a) Fundamental principles of NMR spectroscopy

Zeeman interaction between nuclear spin and the external magnetic field. Vector model of nuclear magnetic resonance: precession, Larmor frequency, resonance condition, and generation of the NMR signal. Free Induction Decay (FID) and Fourier transform. Pulsed experiments. Longitudinal and transverse relaxation times (T₁ and T₂). Sensitivity of magnetically active nuclei. Components and operation of the NMR spectrometer.

b) Chemical shift and spin-spin coupling

Chemical shift and shielding constants. ¹H NMR spectra: signal integration, multiplicity, and coupling constants.

c) Scalar coupling

Origin and interpretation of scalar coupling. First- and second-order spin systems.

d) Heteronuclear NMR

¹³C NMR spectra with and without decoupling. Polarization transfer techniques: INEPT and DEPT experiments.

e) Two-dimensional NMR techniques

Homonuclear correlation experiments (COSY, INADEQUATE) and heteronuclear correlation experiments (HETCOR, HSQC, HMQC, HMBC). Applications to the structural elucidation of complex organic molecules.

f) Nuclear Overhauser effect and related techniques

Nuclear relaxation and Overhauser effect (NOE). Steady-state NOE, spin diffusion, transient NOE, and NOESY. Spin-locking, TOCSY, and ROESY.

g) Dynamic NMR

Dynamic processes observable by NMR. Chemical exchange, conformational phenomena, and molecular kinetics. Influence of dynamics on the shapes and positions of NMR signals. Applications of variable-temperature NMR (VT-NMR) and determination of kinetic and thermodynamic parameters.

Practical Sessions

During the course, hours will be dedicated to practical exercises or simulations, in which strategies for determining the structure of an organic molecule will be presented and applied based on the interpretation of UV, IR, NMR spectra (1D and 2D NMR, both homonuclear and heteronuclear), and mass spectra.

Among other activities, ¹H and ¹³C NMR spectra of organic compounds of natural and synthetic origin will be analyzed using software or real instruments in order to evaluate their structure.

Readings/Bibliography

Spectrometric Identification of Organic Compounds, 8th Edition

R. M. Silverstein, F. X. Webster, D. J. Kiemle, D. L. Bryce,

Wiley, 2014.

 

High-Resolution NMR Techniques in Organic Chemistry

T. D. W. Claridge

Elsevier, 2016.

 

Spectroscopic Methods in Organic Chemistry

S. Bienz , L. Bigler , T. Fox , H. Meier

3° Ed., Thieme, 2021.

 

Spectroscopic Methods in Organic Chemistry

I.Fleming, D. Williams

7° Ed., Springer, 2019.

Teaching methods

Lectures and classroom exercises.

Assessment methods

Learning will be assessed through a main written examination lasting 2 hours, consisting of the identification of a substance on the basis of its IR, UV, NMR — both proton and carbon-13, one- and two-dimensional — and mass spectra. The written examination is considered passed if the structure of the organic compound is correctly identified, and will be awarded a mark of 25/30. The written test will be followed by a brief oral examination, focusing on the analysis and further discussion of topics related to the candidate's written test. The oral examination may confirm or modify the mark by a maximum of plus or minus 5/30.

The examination will be held in person, except in the event of public health emergencies, flooding affecting the country, residence in areas classified as high-risk under the new regulations, and/or student vulnerability, as assessed by the University’s Disability and Specific Learning Disorders (DSA) Service. Each case will be evaluated individually and, where the relevant requirements are met, the examination may be conducted via Microsoft Teams.

Students with specific learning disorders (DSA) or temporary or permanent disabilities are advised to contact the relevant University Office well in advance (https://site.unibo.it/studenti-con-disabilita-e-dsa/it ). The Office will propose any appropriate accommodations to the students concerned. Such accommodations must, however, be submitted to the course instructor for approval at least 15 days in advance. The instructor will assess their suitability, also in relation to the learning objectives of the course.

The use of artificial intelligence is prohibited. Any use of AI constitutes a violation of academic integrity.

Teaching tools

Lectures are delivered using slide presentations.

The teaching material will be made available for download from Virtuale.

Office hours

See the website of Stefano Masiero

See the website of Elisabetta Mezzina