27707 - Organic Chemistry II L

Learning outcomes

At the end of the course the student is able to plan the most appropriate methodology in a multi-step synthetic sequence through basic knowledge of the main reaction types. The student is able to understand the reactivity of the various polyfunctional compounds as well as to describe the requisite methods for achieving their preparation and modification. The central subjects of the course are especially devoted to a careful examination of the selectivity and synthetic efficiency encountered in industrial processes.

Course contents

Contents of the lessons given by Professor Piero Spagnolo

Sterochemistry. Chiral and achiral organic molecules. Chirality due to the presence of chiral carbons. Enantiomers and diastereomers. Meso compounds. Fischer projections of chiral carbons. The R/S naming of chiral carbons. Stereochemical outcome of sin/anti additions to cyclic and acyclic alkenes. Chemical separation (resolution) of enantiomers. Representative examples of enantioselective and diastereoselective syntheses. Chirality in nitrogen, phosphorous and sulfur compounds. Prochirality in planar and tetrahedral compounds. Omotopic, enantiotopic and diastereotopic atoms, groups and faces. Chirality in nature.

Nitrogen compounds. Amines: the naming of amines. Physical and acid-base properties of amines. The acidity and basicity of aliphatic and aromatic amines. Ammonium salts. The synthesis of amines. Alkylation and acylation of amines. Amides. Condensation reactions of amines with aldehydes and ketones. Hofmann eliminations of ammonium salts. Imines, enamines and isocyanates: synthesis and applications. Nitriles and azides: preparation and use in the synthesis of nitrogen compounds. Aromatic amines (anilines): preparation, reactivity and  conversion to arenediazonium salts. Arenediazonium salts as useful synthetic intermediates.

Heteroaromatic compounds. Five- and six-membered electron-rich and electron-poor heteroaromatic compounds. Furan, pyrrole, thiophene and pyridine: electronic structures, chemical properties and general reactivity in electrophilic and/or nucleophilic substitution reactions. Structure and synthetic interest of other peculiar heteroaromatic nitrogen compounds (indoles, quinolines and azoles).

Reactivity of polyfunctional carbonyl compounds. Aldol condensations of aldehydes and ketones; intermolecular Claisen condensations of carboxylic esters and related intramolecular Dieckman condensations. O- and C-alkylations of beta-dicarbonyl compounds. Malonic ester: synthesis, alkylation and decarboxylation. Production of aliphatic esters from malonic ester. Michael additions of beta-dicarbonyl compounds and enamines to electron poor alkenes. Peculiar use of beta- and alfa-dicarbonyl compounds in organic synthesis.

Free Radicals. Generation of carbon and heteroatom centered radicals. Structure and stability of alkyl and aryl radicals and their general reactivity. Chain and non-chain radical reactions. Radical initiators. Polarity, regioselectivity and chemioselectivity in radical reactions. Typical reactions of free radicals: hydrogen and halogen atom abstraction, addition to carbon-carbon double and triple bonds, and alfa- and beta-fragmentation. Radicals in synthesis: radical transformation of functional groups and radical formation of carbon-carbon and carbon-nitrogen bonds. Radical ions: generation in electron transfer processes and their typical reactivity. Radical polymerizations and copolymerizations. Comparative examples of radical and non-radical (heterolytic) processes.

Orbitals and organic chemistry: pericyclic reactions. Basic principles of the pericyclic reactions. Molecular orbitals of pi-bonds in conjugated polyenes. HOMO and LUMO orbitals as frontier orbitals in pericyclic reactions. Electrocyclization reactions of conjugated polyenes: conrotatory and disrotatory electrocylizations under thermal and/or photochemical conditions. Cycloaddition Diels-Alder reactions of butadienes with alkene and alkyne dienophiles in the synthesis of six-membered alicyclic compounds and 1,3-dipolar cycloaddition reactions of organic azides with alkenes and alkynes in the synthesis of five-membered nitrogen heterocycles. Sigmatropic reactions: illustrative examples of thermal or photochemical migrations of hydrogen atoms and alkyl groups in cyclic and acyclic polyenes.

Contents of the lessons given by professor Alfredo Ricci

Protecting Groups. Basic concepts of the use of protecting groups in organic synthesis. Usual reagents for the protection of the more common functional groups. Synthetic applications. 

Oxidation Reactions. General aspects of the oxidation reactions in organic chemistry. Baeyer-Williger oxidative insertion of carbonyl compounds. Oxidation of alkenes: production of epoxides, complete oxidative cleavage, Wacker process. Oxidation of polyols.

Reduction Reactions. General aspects of the reduction reactions in organic chemistry. Major classes of reagents for reductive reactions. Representative examples of synthetc use of organic compound reduction.

Carbohydrates. Natural sources, structures, chemical classification and stereochemistry of carbohydrates. The polyfunctional chemistry of sugars: structural modifications and conversions to common derivatives. Monosaccharides and their derivatives as building-blocks in organic synthesis.

Sulfur and Phosphorous Organometallic Compounds. General comparison of oxygen-, sulfur- and phosphorous-containing organic compounds. The multiple bond in sulfur compounds. Synthesis of chiral sulfur compounds. Sulfur ylides: synthesis, applications and comparison of their chemical reactivity with that of corresponding phosphorous ylides. Organic phosphorous compounds. Phosphorous compounds as nucleophiles. "Biological" chemistry of phosphorous. Representative examples of sulfur and phosphorous compounds of special importance/utility. 

Organic Synthesis Mediated by Organometallic Compounds. General principles of the use of organometallic systems in the formation of carbon-carbon bonds. Polar and poorly polar organometallic reagents. Organometallic transmetallations and their applications in organic synthesis. Stoichiometric reactions. Synthetic use of cuprates. Synthesis of complex organic molecules polyfunctionalized of special interest in medicinal chemistry. Catalytic reactions. Catalysis by metals. Pd-mediated selective formation of C-C bonds: Pd(II)-olefin complexes and their reactions with oxygen nucleophiles. Oxidative addition processes with Pd(0). The Heck reaction: mechanism and use in organic synthesis.

Readings/Bibliography

John McMurry: CHIMICA ORGANICA (seventh edition), 2009, Piccin Nuova Libraria S.p.A., Padova.

Andrew F. Parsons: An Introduction to Free Radical Chemistry, 2000, Blackwell Science Ltd.

Reading material available from the teachers.

Classroom notebook.

Teaching methods

Typical frontal lessons delivered in the classroom with the aid of the blackboard and suitable projection of slides. Classroom solution of problems and answers to exercises relevant to the main topics of the course. 

Assessment methods

Final oral examination

Teaching tools

Suitable use of molecular models for a better understanding of the molecular structures of the more complex organic compounds. Projection of a variety of slides showing a general application of the main synthetic/industrial methodologies which are treated during the course.

Office hours

See the website of Piero Spagnolo

See the website of Alfredo Marco Ricci