00148 - Organic Chemistry

Learning outcomes

The course involves the study of the structure, properties, composition, reactions, and preparation of chemical compounds consisting of primarily carbon and hydrogen, which may contain any number of other elements, including nitrogen, oxygen, sulfur and halogens. Organic compounds are sorted into organic families defined by functional groups representing small structural units within molecules at which most of the compound's chemical reactions occur.

The programme contains also elements of bio-organic chemistry covering amino acids, peptides, proteins, and carbohydrates.

Course contents

1) Covalent bond and molecular geometry:

Structure of the atom. Electronic configuration. Ionization energy. Electronic affinity. Electronegativity. The chemical bond: ionic and covalent. Dipolar moment. Lewis structures. The VSEPR model. Polar and non-polar molecules. Molecular dipole moment. Non covalent bonds. Atomic orbitals. Molecular orbitals. The sigma bond. The pi bond. Hybrid orbitals sp3, sp2, sp. Resonance.

2) Alkanes and cycloalkanes

Molecular formula and sp3 hybridization. Structural isomerism. IUPAC nomenclature. Conformational analysis of ethane, propane, butane. Physical properties. Combustion. Structure and conformation of cycloalkanes with 3, 4, 5 and 6 terms. Chair and boat conformations of cyclohexane: axial and equatorial bonds. Substituted cyclohexanes. Cis / trans isomerism in cyclic compounds.

3) Stereochemistry and chirality

Chiral centers. Enantiomers. Priority rules. Configuration descriptors R, S. Fisher projection. Optical activity. Racemic mixtures. Diastereoisomers. Meso forms. Resolution of enantiomers.

4) Acids and bases

Bronsted-Lowry acids and bases. The acidity constant. Organic acids and bases. Structural factors determining the strength of an acid. Lewis acids and bases. Structure of acid-base adducts.

5) Alkenes

Molecular formula. Cis / trans isomerism. E / Z isomerism. Nomenclature. Thermodynamic stability of alkenes. Heat of hydrogenation. Reaction mechanism. Thermodynamics of chemical reactions. Single stage reaction profile.. Two-stage reaction profile. Intermediates and transition states. Reaction kinetics. First and second order reactions. The rate constant. Meaning of the activation energy and the concept of catalysis The Arrhenius law. Hammond postulate. Nucleophiles and electrophiles.

6) Reactions of alkenes

The electrophilic addition to the C=C double bond. Addition of hydrogen halides. Markovnikov rule. Carbocations. Carbocation transposition. Acid-catalyzed addition of water. Addition of Halogens. Formation of cyclic intermediates. Anti addition. Stereospecific reactions. Hydroboration-oxidation: sin addition, anti-Markovnikov addition. Alkenes reduction: catalytic hydrogenation in heterogeneous phase. Alkenes oxidation: reaction with peracids, osmium tetroxide and potassium permanganate, ozonolysis

7) Alkynes

Structure, hybridization, nomenclature. Electrophilic addition. Addition of hydrogen halides, halogens, acid-catalyzed addition of water and hydroboration-oxidation. Catalytic hydrogenation and reduction with metals. Acidity of terminal alkynes.

8) Haloalkanes, halogenation and radical reactions

Nomenclature, physical properties. Radical intermediates. Stability of alkyl radicals. The radical halogenation reaction of alkanes. Formation of regioisomers. Reactivity and selectivity in the chlorination and bromination reactions of alkanes. Allylic halogenation. The allyl radical. Addition of HBr to alkenes in the presence of peroxides.

9) Nucleophilic substitution and beta-elimination

SN2 mechanism. Transition state. Structure of the haloalkane, of the leaving group, and of the nucleophile. Basicity and nucleophilicity. Stereochemistry of SN2. Protic and aprotic, polar and nonpolar solvents. SN1 mechanism. Stereochemistry of SN1. Effect of the solvent on SN2 and SN1. E2 mechanism. Zaitsev rule. Hofmann rule. Anti stereochemistry. E1 mechanism. Summary of factors influencing nucleophilic substitution and elimination.

10) Alcohols and thiols
Alcohols: structure, nomenclature and physical properties. Acidity. Reaction with metals. Conversion into haloalkanes and alkylsulfonates. SN2 of alkylsulfonates. Dehydration. Oxidation. Thiols: structure and acidity, nomenclature, physical properties. Synthesis and behavior in SN2 reaction. Oxidation reactions.

11) Ethers, epoxides and thioethers
Ethers: structure, physical properties and nomenclature. Preparation of ethers: Williamson synthesis; condensation of alcohols; acid-catalyzed addition of alcohols to alkenes. Reactions of ethers. Oxidation. Epoxides: nomenclature and synthesis. Opening reactions of epoxides. Crown ethers. Thioethers: preparation by Williamson synthesis. 

12) Organometallic compounds
Organolithium, Grignard and organocopper reagents.

13) Aldehydes and ketones
Structure, nomenclature and preparation methods. The nucleophilic acyl addition reaction: addition of Grignard reagents, alkynides, HCN. Addition of water and alcohols. Formation of acetals and hydrolysis. Cyclic hemiacetals. Addition of nitrogen nucleophiles, formation of imines and enamines. Reduction to alcohols and alkanes. Acidity of alpha-hydrogen. Keto enol tautomerism. Oxidation of aldehydes. Alpha-halogenation catalyzed by acids and promoted by bases. Haloformic reaction.

14) Carboxylic acids
Structure, nomenclature and preparation methods, physical properties. Acidity. Reduction. The nucleophilic acyl substitution: formation of acyl chlorides, anhydrides, esters, amides. Lactones and lactams. Hell-Volhard-Zelinski reaction.

15) Carboxylic acid derivatives
Nomenclature of carboxylic acid derivatives and nitriles. Resonance structures and stability. Nucleophilic acyl substitution. Hydrolysis of acid chlorides and anhydrides. Conversion of acid chlorides to anhydrides, esters and amides. Reaction with Grignard reagents. Conversion of anhydrides into esters and amides. Acid and basic hydrolysis of esters. Transesterification. Acid and basic hydrolysis of amides. Formation and hydrolysis of nitriles. Reduction.

16) Enolate anions and enamines
Enolates: alpha-alkylation. Aldol reaction. Claisen condensation. Malonic and acetoacetic synthesis. Unsaturated alpha-beta carbonyl compounds. Resonance. Conjugate addition, Michael reaction.

17) Conjugated systems
Conjugate systems: 1,3 butadiene. 1,2 and 1,4 addition of electrophiles. Kinetic and thermodynamic control.

18) Benzene.
Criteria for aromaticity, Huckel's rule. The cyclopropenyl cation and the cyclopentadienyl anion. Polycyclic aromatic hydrocarbons. Aromatic heterocycles: pyrrole, furan, thiophene, pyridine, and imidazole.

19) Reactions of benzene
Electrophilic aromatic substitution: SEAr: halogenation, nitration, sulfonation, Friedel Crafts alkylation and acylation. Disubstituted benzenes: formation of ortho, meta and para isomers. SEAr: Electronic effect of the substituent. Inductive and mesomeric effects. Orientating effects of the substituent. Cation, radical and benzyl anion. Benzyl radical halogenation. Benzyl oxidation of alkylbenzenes. Aromatic nucleophilic substitution: addition-elimination mechanism and benzine mechanism. Phenols: acidity, effect of substituents. Quinones.

20) Amines
Nomenclature. Basicity of aromatic and aliphatic amines. Basicity of pyridine, pyrrole and imidazole. Preparation methods: alkylation of ammonia and amines; from azides and amides; reductive amination; reduction of aromatic and aliphatic nitro derivatives. Exhaustive methylation of primary amines and Hoffmann elimination. Reactions of aliphatic and aromatic secondary and tertiary amines with nitrous acid. Reactions of primary aromatic amines with nitrous acid. Formation of arendiazonium salts and Sandmeyer reactions.

21) Carbohydrates, amino acids and proteins.
Carbohydrates: monosaccharides, aldoses and ketoses. Configuration: the D and L notation. Configuration of aldoses and ketoses. Epimers. Redox reactions of monosaccharides. Hemiacetal formation. The cyclic structure, alpha and beta anomers. Mutarotation. Glycosides. Reducing and nonreducing sugars. Disaccharides: maltose, cellobiose, lactose, sucrose. Polysaccharides: starch and cellulose.
Amino acids: configuration and acid-base properties. Isoelectric point. Separation of amino acids. Peptides. The peptide bond and the primary structure of proteins. The disulfide bond. The secondary structure of proteins: alpha-helix and beta sheets. Outline of the tertiary and quaternary structure. Synthesis of peptides: protection of the amino group and activation of the carboxylic group.

Readings/Bibliography

- K. P. C. Vollhardt, N. E. Schore, Chimica Organica; 4a Ed., Zanichelli (2016)

- W. H. Brown, C. S. Foote, B.L. Iverson, E. V. Anslyn, Chimica Organica – 5a Ed., EdiSES, 2015

- P. Yurkanis Bruice, Chimica Organica, EdiSES, 2005

- J. Gorzynski Smith, Chimica Organica, McGraw-Hill, 2007.

- B.L. Iverson, S. Iverson, Guida alla soluzione dei problemi da Chimica Organica di Brown, Foote, B Iverson, Anslyn, 4a Ed., EdiSES, 2016.

- T. W. G. Solomons, C. B. Fryhle, R. G. Johnson, La chimica organica attraverso gli esercizi

Teaching methods

Theoretical lessons

Assessment methods

Written text lasting 90 minutes and oral examination. Both the text and the exam will concern the programme topics covered in class.

The written test consists of six open questions. The questions aim to verify the theoretical knowledge, the reactivity of the functional groups of an organic molecule, the ability to choose the reagents, and to identify the products of a reaction. Each question allows to obtain a maximum of one point. The minimum score which allows access to the oral exam is three points. The oral exam focuses on the identification of the products and on the exposition of the mechanisms of the main organic reactions. The duration of the oral exam is 30 minutes. The final grade represents an average of the performances of the two tests.

Teaching tools

PowerPoint slides

Office hours

See the website of Elisabetta Mezzina