ORGANIC CHEMISTRY I

The course aims to provide a critical and scientific mentality and rational use of mnemonic abilities, favoring the ability to apply theoretical knowledge to problem-solving.

This means overcoming the limit of mere "mnemonic repetition" of concepts that, in doing so, would be aimed at simple learning. Critical and scientific mentality at the same time constitute a high-level objective; it requires a synthesis between mental operation and actual realization: the first is expressed in the design of an experiment, in the rational-intuitive control of the execution and calculation phases and the evaluation phase of the results; the second is expressed in the actual execution of the experiment, even at the virtual level.

Therefore, at the end of the course, the student must be able to:

D1 KNOWLEDGE AND UNDERSTANDING ABILITY

• Know in-depth the reactivity of new classes of organic compounds and the reaction mechanisms through which they react.

• Illustrate the criteria that allow to carry out processes with a pronounced chemical, positional, and stereochemical selectivity.

D2 ABILITY TO APPLY KNOWLEDGE AND UNDERSTANDING

• Identify the nature of the synthetic process to which the organic molecules are subjected based on the described reaction conditions.

• Correctly describe the reaction mechanism for the related processes.

• Discuss the nature of the selective processes that these mechanisms involve.

D3 AUTONOMY OF JUDGMENT

• Choose the most suitable reagents to carry out the required synthetic process with the desired selectivity degree.

• Use the most efficient method available to perform the synthesis of even multi-functionalized structures.

D4 COMMUNICATION SKILLS

• Communicate, using appropriate technical-scientific terminology, with the teacher and experts in the subject of study.

• Competently discuss, even in the context of an oral examination, the synthetic techniques learned.

D5 LEARNING SKILLS

• Find and learn the information, new compared to those provided during the training activity, necessary to broaden the knowledge on topics more or less correlated with those covered by the course.

• Understand and process the contents of scientific publications containing the results of new research.

• Use the knowledge acquired to make it easier to understand topics related to organic chemistry delivered in other educational activities.

The course activities consist of lectures and classroom exercises. To these will be added some "case studies" concerning molecules of chemical-pharmaceutical interest. The student is required to actively participate in the discussion of the topics presented and in particular, in the case studies.

Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes with respect to previous statements, in line with the programme planned and outlined in the syllabus.

Learning assessment may also be carried out on line, should the conditions require it.

MODULE 1. INTRODUCTION TO THE STUDY OF ORGANIC CHEMISTRY

1. ELEMENTS OF GENERAL CHEMISTRY: ELECTRONIC STRUCTURE AND BOND

Structure of the atom - Distribution of electrons in the atom - Covalent bonds - Representations of the structure of a compound - Atomic orbitals - Introduction to the theory of molecular orbitals - Formation of single bonds in organic compounds - Formation of the double bond: the bonds of ethene - Formation of the triple bond: the bonds of ethine - The bonds of the methyl cation, of the methyl radical and of the methyl anion - The bonds of ammonia and ammonium ion - The bonds of water - The bonds of halogenhydric acids - Hybridization and molecular geometry - Summary: hybridization, bond length, bond strength and bond angles - Dipolar moments of molecules.

2. ACIDS AND BASES: FUNDAMENTAL CONCEPTS IN ORGANIC CHEMISTRY

Introduction to acids and bases, pK and pH - Organic acids and bases - How to predict the outcome of an acid-base reaction - How to determine the position of an equilibrium - Influence of the structure of an acid on its pK value - Influence of substituents on the strength of an acid - Introduction to the delocalized electrons - Summary of the factors that determine the power of an acid - Influence of the pH on the structure of an organic compound - Buffer solutions - Lewis acids and bases - Acids and bases.

3. INTRODUCTION TO ORGANIC COMPOUNDS: NOMENCLATURE, PHYSICAL PROPERTIES, AND STRUCTURE

Alkyl groups - Nomenclature of alkanes - Nomenclature of cycloalkanes - Nomenclature of alkyl halides - Nomenclature of ethers - Nomenclature of alcohols - Nomenclature of amines - The structure of alkyl halides, alcohols, ethers and amines - Non-covalent interactions - Solubility of organic compounds - Rotation around the single carbon-carbon bond - Cycloalkanes and ring tension - Cyclohexane conformers - Monosubstituted cyclohexane conformers - Unsubstituted cyclohexane conformers - Cyclohexane condensates.

MODULE 2. ELECTROPHILES, STEREOCHIMICS AND ELECTRONIC DELOCALIZATION REACTIONS

4. ISOMERS: THE ARRANGEMENT OF ATOMS IN THE SPACE

Cis-trans isomers - Nomenclature E, Z of the isomers of an alkene - Chirality - An asymmetric center generates chirality in a molecule - Isomers with an asymmetric center - Asymmetric centers and stereocenters - Representation of enantiomers - Naming of enantiomers with descriptors R, S - Optical activity of chiral compounds - Measurement of specific rotation - Enantiomeric excess - Compounds containing more than one asymmetric center - Stereoisomers of cyclic compounds - Meso compounds - Chiral compounds without stereocentres: Atropisomers - Nomenclature of compounds containing more than one asymmetric center - Nitrogen and phosphorus can be asymmetric centers - Receptors - The separation of enantiomers.

5. ALKENES: STRUCTURE, NOMENCLATURE, AND INTRODUCTION TO REACTIVITY • THERMODYNAMICS AND KINETICS

Molecular formulas and degree of unsaturation - Alkenes nomenclature - Alkenes structure - Reactivity of organic compounds and functional groups - Alkenes reactivity • Use of curved arrows - Thermodynamics: how much product is formed? - Increase the amount of product in a reaction - Calculate the values of ∆H - Use ∆H values to determine the relative stability of alkenes - Kinetics: how fast do the products form? - Speed of a chemical reaction - Diagram of free energy as a function of the reaction coordinate - Catalysis - Enzymatic catalysis.

6. THE REACTIONS OF THE ALKENES • THE STEREOCHIMIC OF THE ADMISSION REACTIONS

Addition of hydrogen halide to alkenes - Stability of carbocations - Structure of the transition state - Regioselectivity of electrophilic addition reactions - Addition of water to alkenes - Addition of alcohol to alkenes - Transposition of carbocations - Oxyacuriation-Addition of borane to alkenes: hydroboration - oxidation - Addition of halogens to alkenes - Addition of a peroxy acid to alkenes - Addition of ozone to alkenes: ozonolysis - Regioselective, stereoselective and stereospecific reactions - Stereochemistry of electrophilic addition reactions - Cyclic alkenes - Stereochemistry of reactions catalysed by enzymes - Differentiation of enantiomers by biological molecules - Chiral catalysts - Reactions and synthesis - Sin-hydroxylation - Oxidative splitting.

7. THE REACTIONS OF ALKINES • INTRODUCTION TO MULTISTAGE SYNTHESIS

Alkynes nomenclature - Nomenclature of compounds that contain more than one functional group - Alkynes structure - Physical properties of unsaturated hydrocarbons - Alkynes reactivity - Addition of halogenhydric acids and halogens to alkynes - Addition of water to alkynes - Hydroboration-oxidation of alkynes - Addition of hydrogen to alkynes - Acidity of a hydrogen bound to a carbon sp - Use of acetylide ions in organic synthesis - SYNTHETIC STRATEGY I: Introduction to multistage synthesis.

8. ELECTRONIC DELOCALIZATION AND ITS EFFECT ON STABILITY, pK_a AND PRODUCTS OF A REACTION • AROMATICITY, ELECTRONIC EFFECTS AND INTRODUCTION TO BENZENE REACTIONS

Delocalized electrons explain the structure of benzene - The bonds in benzene - Resonance limit structures and resonance hybrid - How to draw the structures of resonance limit - Predict the stability of the structures resonance limit - Resonance energy - Electronic delocalization increases stability - Stability according to the theory of molecular orbitals - Effect of electronic localization on pK_a - Electronic effects - Electronic delocalization can influence the product of a reaction - Reactions of dienes - Thermodynamic control and kinetic control - Diels – Alder reaction: an addition reaction 1,4 - Retrosynthetic analysis of the Diels-Alder reaction - Benzene is an aromatic compound - The two criteria for aromaticity - Application of aromaticity criteria - Aromaticity according to the theory of molecular orbitals - Aromatic heterocyclic compounds - Benzene reactivity- Classification of the reactivity of organic compounds I.

MODULE 3. REPLACEMENT AND ELIMINATION REACTIONS

9. REPLACEMENT REACTIONS AND ELIMINATION OF ALKYLENE HALOGEN

The S_N2 reaction - Factors influencing S_N2 reactions - The SN1 reaction - Factors influencing S_N1 reactions - Competition between S_N2 and S_N1 reactions - Alkyl halide elimination reactions - E2 reaction - E1 reaction - E1 and E2 reaction competition - The stereoselectivity of E2 and E1 reactions - Elimination from substituted cyclohexanes - Predict the reaction products of an alkyl halide with a nucleophile/base - Benzyl, allyl, vinyl and aryl halides - Solvent effects - Substitution and elimination reactions in the synthesis organic - Competition between intermolecular reactions and intramolecular reactions - SYNTHETIC STRATEGY II: How to deal with the problem.

10. REACTIONS OF ALCOHOLS, ETERS, EPOXYS, AMINES AND COMPOUNDS CONTAINING SULFUR

Nucleophilic substitution reactions of alcohols: formation of alkyl halides - Lucas's essay - Other methods used to convert alcohols into alkyl halides - Conversion of an alcohol into a sulphonic ester - Alcohol elimination reaction: dehydration - Biological dehydration - Oxidation of alcohols - Reactions of nucleophilic substitution of ethers - Reactions of nucleophilic substitution of epoxides - Ethers corona: another example of molecular recognition - Corona ethers can be used to catalyze reactions SN2 - Arenes oxides - Benzo [a] pyrene and cancer - Chimney sweeps and cancer - Amines do not undergo nucleophilic or elimination substitution reactions - Quaternary ammonium hydroxides undergo elimination reactions - Tiols, sulfides and sulfonium ions - Mustard gas: a chemical agent of war - Alkylating agents such as drugs against cancer - Methylating agents Eliminate termites - S-adenosylmethionine: an antidepressant - Classification of reactivity of organic compounds II.

11. ORGANOMETALLIC COMPOUNDS OF LITHIUM, MAGNESIUM, AND COPPER

Organolithium and organomagnesium compounds - Transmetallation - Organocuprates.

12. THE RADICALS

Reactivity of alkanes - Natural gas and oil - Fossil fuels: a problematic energy source - Chlorination and bromination of alkanes - Stability of radicals - Product distribution depends on probability and reactivity - The principle of reactivity-selectivity - Training of explosive peroxides - Addition of radicals to alkenes - Stereochemistry of radical substitution and addition reactions - Radical substitution of allyl and benzyl hydrogens - Cyclopropane - SYNTHETIC STRATEGY III: Examples of multi-stage synthesis - Radical reactions in biological systems - Radicals and stratospheric ozone.

MODULE 4. CARBONYL COMPOUNDS

15. REACTIONS OF CARBOXYLIC ACIDS AND CARBOXYLIC ACID DERIVATIVES

Nomenclature of carboxylic acids and carboxylic acid derivatives - Structure of carboxylic acids and carboxylic acid derivatives - Physical properties of carbonyl compounds - How carboxylic acids and carboxylic acid derivatives react - The relative reactivity of carboxylic acids and acid derivatives carboxylic acid - Reactions of acyl halides - Reactions of esters - Hydrolysis and transesterification of acid-catalyzed esters - Hydrolysis of esters favored by the hydroxide ion - Reactions of carboxylic acids - Reactions of amides - Hydrolysis and alcoholysis of amides catalysed by ions hydroxide of amides - Hydrolysis of an imide: Gabriel's synthesis of primary amines - Nitriles - Carboxylic acid anhydrides - Dicarboxylic acids - Chemical activation of carboxylic acids - Biological activation of carboxylic acids.

22. THE CATALYSIS IN ORGANIC REACTIONS

Catalysis in organic reactions - Acid catalysis - Basic catalysis - Nucleophilic catalysis - Catalysis with metal ions - Intramolecular reactions - Intramolecular catalysis.

16/23. REACTIONS OF ALDEHYDES AND KETONES • FURTHER REACTIONS OF DERIVATIVES OF CARBOXYLIC ACIDS

Nomenclature of aldehydes and ketones - Relative reactivity of carbonyl compounds - Reactivity of aldehydes and ketones - Reactions of carbonyl compounds with carbon nucleophiles - Reactions of carbonyl compost with hydride ion - Further information on reduction reactions - Chemoselective reactions - Reactions of aldehydes and ketones with nitrogen nucleophiles - Reactions of aldehydes and ketones with oxygen nucleophiles - Protecting groups - Reactions of aldehydes and ketones with sulfur nucleophiles - Reactions of aldehydes and ketones with a peroxy acid - Wittig reaction - SYNTHETIC STRATEGY IV: Disconnections, synthons and synthetic equivalents - Nucleophilic addition to de, -unsaturated aldehydes and ketones - Nucleophilic addition to unsaturated carboxylic acid derivatives - Conjugated addition reactions in biological systems.

17. CARBON REACTIONS

Acidity of hydrogen - Keto-enolic tautomers - Keto-enolic interconversion - Carbon halogenation de of aldehydes and ketones - Carbon halogenation of carboxylic acids - Formation of an enolate ion - Carbon alkylation  - Alkylation and carbon acylation  through an enzyme intermediate - Carbon alkylation  - An aldolic addition forms a -hydroxyaldehyde or a-hydroxyketone - The dehydration of an aldol additive product forms aldehydes and ketones ,-unsaturated - Cross aldol addiction - Claisen condensation : -ketoesters formation - Other crossed condensations - Condensation and intramolecular additions - Robinson's ring - -ketoacid decarboxylation - Malonic synthesis - Acetacetic synthesis - SYNTHETIC STRATEGY V: Formation of new carbon-carbon bonds - Carbon reactions  in biological systems.

MODULE 5. AROMATIC COMPOUNDS

18. REACTIONS OF BENZENE AND SUBSTITUTE BENZENES

Nomenclature of monosubstituted benzenes - General mechanism of reactions of electrophilic aromatic substitution - Benzene halogenation - Benzene nitration - Benzene sulphonation - Friedel-Crafts acylation of benzene - Friedel-Crafts alkylation of benzene - Alkylation of benzene by acylation-reduction - Use of coupling reactions in benzene alkylation - Chemical transformations of substituents on the benzene ring - Nomenclature of disubstituted and polysubstituted benzenes - Effect of substituents on reactivity - Effect of substituents on orientation - The ortho-para relationship - Further considerations on effects of the substituents - SYNTHETIC STRATEGY VI: Synthesis of mono and disubstituted benzenes - Synthesis of trisubstituted benzenes - Use of diazonium salts for the synthesis of substituted benzenes - Azobenzenes - Mechanism of the formation of a diazonium ion – Aromatic nucleophilic substitution - SYNTHETIC STRATEGY VII: Synthesis of cyclic compounds.

19. ADMINISTRATIONS

Nomenclature - Acid-base properties of amines - Amine reactivity as bases and as nucleophiles - Amine synthesis - Hofmann transposition - Curtius transposition - Cope elimination - Mannich synthesis - Heterocyclic amines of biological importance.

19/29/30. CHEMISTRY OF HETEROCYCLIC COMPOUNDS AND AROMATIC HETEROCYCLES

Classification of aromatic heterocycles - Heteroaromaticity - Electrophilic substitution: general aspects - Electronic systems: pentatomic heterocycles containing only one heteroatom - Preparation: Paal-Knorr synthesis of furan, pyrrole and thiophene - Synthesis of pyrrole Knorr - Synthesis of Feist-Bernary del furan and pyrrole Hantzsch synthesis - Reactivity: Acid-base, electrophilic substitution, addition and cycloaddition, oxidation and reduction reactions - Electron systems: benzocondensed pentatomic heterocycles containing only one heteroatom - Preparation: Fischer synthesis of indole - Reactivity: Acid-base, electrophilic substitution, oxidation and reduction reactions - Electron poor systems: exatomic heterocycles containing only one heteroatom - Preparation: Hantzsch synthesis of pyridine - Reactivity: Acid-base reactions, Nitrogen reactions with electrophiles , Electrophilic replacement reactions , of nucleophilic substitution, of oxidation and reduction - Pyridine N-oxide and electrophilic substitution - Electron-poor systems: benzocondensed heterocyclic heterocycles containing only one neutral heteroatom - Preparation: Skraup synthesis of quinoline, Bischler-Napieralski synthesis of isoquinoline - Reactivity: Main reactions.

1. Organic Chemistry – P. Y. Bruice – 8ª Ed. Pearson.
2. Organic Chemistry – J. Clayden, N. Greeves, and S. Warren – 2^nd Ed. Oxford University Press.