ORGANIC CHEMISTRY II

The course aims to broaden the knowledge of Organic Chemistry acquired in the first course, paying attention to the nomenclature, chemical properties and reactivity of polyfunctional compounds, and of the main classes of organic compounds of biological relevance: carbohydrates, amino acids and peptides, lipids; of the main heterocyclic systems. Furthermore, advanced organic synthesis reactions will be studied, learning to develop simple synthetic sequences of polyfunctional organic compounds and to apply the principles of modern synthetic strategies: disconnection approaches, carbon-carbon bond formation, deprotection/protection of functional groups.

Lectures

Enols and enolates

Keto-enol tautomerism - enolization catalyzed by acids and bases - stability of enols - Hydrogen acidity in carbonyl alpha - enolate anions - Lithium-oxides - Aldehyde and ketone alpha carbon halogenation - Aloform reaction - Carbon halogenation of carboxylic acids –– Alkylation of alpha carbon– Alkylation and acylation of alpha carbon by means of an enzyme intermediate - Aldol condensation: Dehydration of an aldol condensation product - Cross aldol condensation - Mannich reaction - Claisen condensation: formation of ß-ketoesters - Other crossed condensations - - Robinson reaction - Decarboxylation of ß-ketoacids - Malonic synthesis - Acetacetic synthesis

Alpha-beta unsaturated carbonyls

Conjugation effects - addition reactions - Beta carbon alkylation - Michael reaction - Nucleophilic carbonyl or conjugate attack - "hard" and "soft" nucleophiles - - reactions with ammonia and amines - reactions with alcohols and thiols - reactions with organometallic compounds and effect of Cu (I) salts - addition of enolates - addition followed by cyclization in the ring synthesis

Saturated heterocyclic compounds

Epoxides, aziridines, azirines and tiiranes

Aromatic Heterocycle Compounds

Classification of aromatic heterocycles - Heteroaromaticity - 5 ​​and 6 terms heteroaromatic rings with a heteroatom: Furan, pyrrole, thiophene and pyridine. Synthesis from 1,3 and 1,4-dicarbonyls Heteroaromatic compounds with two or more heteroatoms - benzocondensed heteroaromatic compounds - Electrophilic aromatic substitution reactions, aromatic nucleophilic substitution, oxidation and reduction - N-oxide pyridine and electrophilic substitution.

Carbohydrates

Classification of carbohydrates - The D and L notation - Configuration of aldoses - Configuration of ketoses - Reactions of monosaccharides in basic solution - Oxidation-reduction reactions of monosaccharides - Chain elongation: Kiliani-Fischer synthesis - Chain shortening: degradation of Wohl - Monosaccharides form cyclic hemiacetals - Glycosides formation - The anomeric effect - Reducing and non-reducing sugars - Mutarotation - Disaccharides - Polysaccharides.

Amino acids, peptides and proteins

Amino acid nomenclature - Amino acid configuration - Acid-base properties of amino acids - The isoelectric point - Amino acid separation - Amino acid synthesis methods - Resolution of a racemic amino acid mixture - Peptide bonds and disulfide bonds - Peptide synthesis strategies - Peptide synthesis - Introduction to the structure of proteins - How to determine the primary structure of a polypeptide or a protein - Secondary structure of proteins - Tertiary structure of proteins - Quaternary structure of proteins.

Cycloadditions and pericyclic reactions

Conjugated dienes, molecular orbitals and symmetry, electrocyclic reactions, cycloadditions, sigmatropic transpositions, electrophilic additions, Dies-Alder, pericyclic reactions

Organometallic compounds and formation of new C-C bonds

C-C coupling reactions: covalent synthetic methodologies of new C-C bonds. Suzuki, Stille, Heck, Sonogashira, Negishi. Formation of new bonds C = C: Metathesis; Click Chemistry

NMR spectroscopy

Fourier transform NMR, screen effect, signal multiplicity, chemical shift, diamagnetic anisotropy, signal integration, coupling constants. 13C NMR spectroscopy, two-dimensional NMR spectroscopy.

PHYSICAL METHODS IN ORGANIC CHEMISTRY

General principles of absorption spectroscopy. UV-VIS and IR spectroscopy. General principles and examples of applications to organic molecules.

Gas chromatography. Essential factors inherent in the gas chromatographic technique. Chromatographic columns. High pressure liquid chromatography (HPLC). General principles.

LABORATORY EXERCISES

Use of TLC for the identification of different organic substances present in a mixture: how do we proceed to choose the most suitable eluent mixture?
Electrophilic aromatic substitution: p-nitroaniline synthesis (protecting groups):
Separation of ortho- and para-nitro-aniline by chromatographic column .
Para-nitroaniline purification by crystallization
Multistep synthesis: preparation of a local anesthetic (benzocaine):
Synthesis and characterization of N-acetyl-p-toluidine (nucleophilic acyl substitution)
Synthesis and characterization of para-acetamidobenzoic acid (oxidation with KMnO4; reduction of oxide reactions in organic chemistry)
Synthesis and characterization of benzocaine (para-amino benzoic acid) (acid hydrolysis of a peptide bond)
All the products obtained will be: isolated, purified (distillation, crystallization, column chromatography or PLC) and characterized.

The characterization of the prepared compounds will be performed by: m.p.; UV-Vis; IR; 1H-NMR and 13C-NMR.

Notes from lessons

• P. Y. BRUICE - Chimica organica - 2a Edizione EdiSES
• W.H. BROWN e altri autori - Chimica Organica 5a Edizione EdiSES
• Donald L. Pavia, Gary M. Lampman, George S. Kriz Jr. “Introduction to Spectroscopy”, Saunders College Publishing; “Il Laboratorio di Chimica Organica”, Sorbona, Milano
• Stuard Warren “Designing Organic Syntheses”, John Wiley &Sons
• M. Hesse, H. Meier, B. Zeeh “Metodi Spettroscopici nella Chimica Organica”, Edises, Napoli
• G.F. Pedulli “Metodi Fisici in Chimica Organica”, Piccin, Padova
• M.R. Royston, J.C. Gilbert, S. F. Martini; “Chimica Organica Sperimentale”, Zanichelli
• R.M. Silverstein, F.X. Webster; “Identificazione Spettroscopica di Composti Organici”, Ambrosiana
• Marco D’Ischia “La Chimica Organica in Laboratorio”, Piccin, Padova