PHYSICAL ORGANIC CHEMISTRY AND PHYSICAL METHODS IN ORGANIC CHEMISTRY

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

Single discipline educational activity

Course Sheet

Course code:

COFM10

Academic Year of enrolment:

2021

Year of supply:

2023/2024

Type of Course:

Related/Supplementary

Degree:

Course of Single Cycle Degree 5 years in MEDICINAL CHEMISTRY AND PHARMACEUTICAL TECHNOLOGY

Disciplinary Sector:

Organic Chemistry

Language:

Italian

Location:

CHIETI

Credits:

Programme Year:

Professor and Collaborators:

CIULLA MICHELE

FONTANA Antonella

DI PROFIO Pietro

Cycle:

Second semester

Obligatory attendance:

Yes

Minimum hours of attendance:

Hours of classroom activity:

Individual study hours:

147

Prerequisites:

* Organic Chemistry II
* Physical Chemistry
In fact, the student must have in mind the reactivity of organic compounds and therefore must have passed the examination of Organic Chemistry I and Organic Chemistry II. Furthermore, the student must have clear basic concepts of Physical Chemistry

Objectives

The treatment of the linear relations of free energy aims to introduce the student, on a rigorous basis, to the correlations structure-biological activity. In fact, these relationships have proved to be of fundamental importance in the research and development of new substances that are famacologically active. The practical applications of thermodynamics and kinetics to various aspects of organic chemistry, the study of the methods that allow to go back to the mechanism of reactions and the evaluation of the most appropriate solvent and catalyst allow the student to form a cultural baggage essential for the graduate in CTF
The techniques of nuclear magnetic resonance, mass spectrometry and IR spectrophotometry are the fundamental baggage for those who need to determine the structure of organic compounds. The knowledge of these techniques is therefore essential for the graduate in C.T.F., and the course aims to provide him with sufficient theoretical bases for the understanding of NMR, IR and MS spectra, especially as regards the complex theoretical aspects related to nuclear magnetic resonance. Another formative objective of the course is to provide the student with a first practical knowledge of the procedures and experimental approaches for the correct analysis of spectroscopic data that can be obtained in the process of elucidation of the structures of organic molecules.

Contents

• Thermodynamics and kinetics
• Linear free energy correlations (LFER)
• Isotope effect
• Solvent effect
• Acids and bases
• Acid-base catalysis
• Basic principles of nuclear magnetic resonance (NMR)
• Proton and carbon 1D-NMR spectrometry
• 2D-NMR
• Mass spectrometry
• IR spectrophotometry
• Raman spectrometry

Extended Syllabus

• Thermodynamics and kinetics: Rate laws - Reactions of I, II and III order - Equilibrium and consecutive reactions - Approximation of the rate determining step - Steady-state approximation - Arrhenius equation - Eyring equation - Potential energy surfaces and diagrams of reaction - More O'Ferrall-Jencks Graphs - Hammond Postulate - Principle of microscopic reversibility - Principle of reactivity-selectivity - Principle of Curtin-Hammett
• Linear free energy correlations (LFER): Hammett equation: substituent and reaction constants – Variations to Hammett scale - Non-linear Hammett correlations - Multiparameter LFER: the equation of Yukawa-Tsuno - Taft-Ingold equation for aliphatic systems - Biological activity correlations: QSAR
• Isotope effect: kinetic and equilibrium isotope effect - Primary, secondary and solvent isotopic effects - Tunnel effect
• Solvent effect: properties of solvents - Non-covalent interactions –Non-conventional solvents: ionic liquids and supercritical fluids - Solvation and electrostriction - Dielectric constant and Hildebrand constant- Grunwald-Winstein Y scale - Solvatocromism: Kosower Z and Dimroth and Reichardt ET(30) - Gutmann Scale - Abraham-Kamlet-Taft scale - Preferential solvation - Hydrophobic interaction and "iceberg" theory
• Acids and bases: Hammett acidity function – Excess acidity and basicity functions - Nucleophiles and electrophiles: hard-soft principle
• Acid-base catalysis: Specific and general acid-base catalysis - Electrophilic and nucleophilic catalysis - Brønsted equation - Theory of Marcus - Rate-pH profiles.
• Basic principles of nuclear magnetic resonance: magnetic properties of nuclei, excitation and relaxation. Acquisition methods. Base sequences. FID and Fourier transform. Continuous wave and pulsed methods (Pulse-FT-NMR).
• 1-Dimensional NMR spectrometry: proton spectroscopy (1H-NMR): chemical shift, spin coupling, first-order and higher order spin systems. Chemical and magnetic equivalence. Exchangeable protons. Selective spin decoupling. Chirality in 1H-NMR spectroscopy. The nuclear Overhauser effect (NOE): difference spectra, estimates of internuclear distances.
• NMR spectrometry of carbon-13 (13C-NMR): 1H-13C coupling. Decoupled spectra. DEPT sequence. Chemical shift. Other important groups (31P, 15N-NMR).
• Two-dimensional NMR spectrometry:
1H-1H COSY and TOCSY correlation, NOESY correlation 1H-1H, 1H-13C HETCOR and HMQC correlation, 13C-13C INADEQUATE correlation.
• Mass spectrometry:
Physical principles. Instrument: sample introduction, ionizing sources, analyzers, detectors. Types of ions generated. Patterns of fragmentation and rearrangements. Information obtained from a mass spectrum. • IR spectrophotometry: theoretical foundations and recognition of the main functional groups.
Application of mono- and two-dimensional NMR spectrometric techniques, mass spectrometry and IR spectroscopy to the structural determination of organic compounds.
• Raman spectroscopy: theoretical foundations, Raman scattering of the most important functional groups. Exercises

Recommended Bibliography

• Isaacs "Physical Organic Chemistry", Pearson
• Molteni "Elementi di Chimica Organica Fisica", Aracne Editrice
• Silverstein, Webster, Kiemle “Identificazione spettrometrica di composti organici” 2nd ed., Ambrosiana.
• Chiappe, D’Andrea “Tecniche spettroscopiche e identificazione di composti organici”, Edizioni ETS
• Friebolin "Basic One- and Two-Dimensional NMR Spectroscopy", 4th ed., Wiley-VCH

Methods of Provision

Conventional

Teaching Methods

The course consists of 9 CFU divided in 64 hours of traditional lessons and 12 hours of guided exercises in the classroom.

Evaluation methods

Verification of learning:

The exam consists of a written test for each module. The written tests include the evaluation of reaction mechanisms on the basis of experimental data of different nature, the full mastery of kinetic laws and thermodynamic evaluations, the analysis of data in non-ideal systems, the interpretation of spectra obtained with various techniques, and the provision of spectral figures based on the forecast procedures and theoretical aspects covered by the course. The candidate pass the exam if he reaches a minimum score of 18/30 in both modules. The final mark of the exam is the average between the marks of the two written tests.
For foreign students the exam can be written in English (both questions and answers)

Contacts/More Information

The slides projected in the classroom during the course are available in PDF format on the website of the two courses.
The teacher is also available in the reception timetable for further clarification on the topics covered in class.

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

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