Pharmacy

A- Richiami Di Chimica Di Base. A- Revision of basic chemistry concepts. Electronic configuration of elements and octet rule. Electronic spin, exclusion principle of Pauli and principle of maximum multiplicity. Ionic and covalent (homopolar, polar and dative). Chemical bonds. Polarity of bonds and molecules. Strength and binding energy. Bond length and bond angle. Formal charge and oxidation number of atoms in organic compounds. REDOX reactions in organic chemistry. Atomic and molecular orbitals. Hybrid Orbitals sp, sp2, sp3. Definition of acid and base species according to Arrhenius, Bronsted-Lowry and Lewis theories. Intra- and inter-molecular forces: hydrogen bond and van der Waals bond. Homolytic and heterolytic bond cleavage. Heterolysis of carbon bonds: formation of carbocations and carbanions. Homolysis of carbon bonds: formation of free radicals. B- Molecular structure. B1-Definition (constitution and stereochemistry). Representation of organic molecules by means of Lewis and Kekulè structures, both in compact and corner-line version. Definition of resonance and rules for writing correct resonance structures of organic molecules. Functional groups and their possible electrophilic / nucleophilic properties. B2-Stereochemistry. Molecular symmetry: essential concepts (centers, planes and proper and improper axes of symmetry). Essential concepts concerning the stereochemistry of organic molecules. Classification: constitutional and steric isomerism. Diastereomers and enantiomers. Differences of conformational and configurational nature. Optical and geometric stereoisomerism. Stereogenic centers, axes and planes. Molecular chirality and elements responsible for it (centers, axes and planes). Racemic and scalemic mixtures. Configurational descriptors cis/trans, E/Z, R/S. Cahn-Ingold-Prelog rules. Fischer projections of organic molecules (rules for their correct writing and manipulation). Mesoforms. Epimers. Optical activity of chiral molecules. Relative configuration of asymmetric centers in monosaccarides and alpha-amino acids: D / L descriptors. Outlines on the resolution of enantiomers. C- Classes of Organic Compounds C1- Hydrocarbons Linear and cyclic Alkanes. Sp3 hybridisation of all the carbon atoms (tetrahedral carbons). Nomenclature, chemical-physical properties and stability of the possible conformations (contributions afforded to the energy structure by angular, torsional and steric tension). Cis/trans isomerism in cycloalkanes. Insights on the structure of the Cyclohexane and of its derivatives: chair and boat conformations, hydrogens and substituents in axial and equatorial positions. C2- Alkenes, Polyenes and Alkynes: presence of carbon atoms involved within multiple bounds (double and triple bonds, respectively). Planar and linear geometry locally conferred by the sp2 and sp hybridisation characterizing the carbon atoms involved into multiple bonds. Nomenclature and chemical-physical properties. Stereochemistry related to the presence of double bonds (geometric isomerism). Differential stability of alkenes isomers (hyperconijugation). Nucleophile properties associated to pi-greek electrons, conjugation effects between unsaturated bonds. C3- Aromatic hydrocarbons. Concept of aromaticity: rules for its identification (Huckel's rule). The Benzene molecule. Nomenclature of benzene derivatives. Aromaticity of some important heterocyclic molecules (pyridine, pyrrole, furan, thiophene, quinoline, indole, imidazole, purine, pyrimidine). Conjugated cyclic polyenes (Annulenes). C4- Alkyl, vinyl and aryl halides: structure, nomenclature and chemical-physical properties. Electrophilic character of the halogen-substituted carbon within alkyl halides. C5- Alcohols and thiols, phenols and thiophenols, ethers and sulfides: structure, nomenclature, physical and chemical-physical properties, acid-base properties. Nucleophilic character of the heteroatom. Epoxides as a special case of strongly reactive ethers (electrophilic character of the carbon atoms bonded to the epoxidic oxygen). C6- Aliphatic and aromatic amines, imines and enamines. Structure, nomenclature, chemical-physical and acid-base properties. Factors that influence their acidity and basicity. Nucleophile properties of the nitrogen atom. C7- Organometallic compounds. Grignard and lithium organ reagents. General structure, nomenclature, physical and chemical properties. Reactions typically employed for their synthesis: a) alkyl, vinyl or aryl halides in presence of a strongly electropositive metal; b) transmetallation reactions. Basic and nucleophilic behavior of the metal-bound carbon atom. C8- Carbonyl compounds, and related species: aldehydes, ketones, carboxylic acids, acyl halides, esters, amides, anhydrides, nitriles. Structure, nomenclature, physico-chemical properties and acid-base properties of these species. Factors responsible for the peculiar acidity possessed by the carboxylic group and by the hydrogens linked to carbons alpha to carbonyl moieties (aptitude to enolate ion formation). Tautomeric equilibria. Electrophilic character of the carbonyl-carbon. Nucleophilic properties of the enolate ion and of the neuter enol forms. Nomenclature of salts of carboxylic acids. D- Reactions involved in transformation and preparation of compounds belonging to the various classes of organic compounds. D1- Reactions classification based on the involved mechanism (radical, polar, pericyclic reactions) and on the number of reacting and formed species (addition, substitution, elimination and rearrangement reactions). Thermodynamic quantities involved in reactions (outlines). Energy diagrams that describe the variations of such quantities as a function of the reaction coordinate. Kinetic quantities involved in organic reactions (outlines). Elementary and composed reactions, monomolecular and bimolecular. Reaction order. Relationship between velocity constants and equilibrium constant (outlines). D2- Radical reactions. Halogenation of alkanes (substitution of alkanic hydrogens) and alkenes (substitution of allylic hydrogens) and relevant radical mechanisms involved. Regioselectivity of substitution in halogenation of alkanes. Stability of alkyl radicals. Principle of reactivity-selectivity: Hammond's postulate in the interpretation of the different selectivity between chlorination and bromination reactions. Addition of HBr to alkenes governed by radical mechanism. Polymerization governed by radical mechanism. Stereochemistry involved in substitution reactions governed by radical mechanism. D3- Addition reactions to alkenes and alkynes. Electrophilic addition to the double bond of hydrogen halides (formation of carbocations and their stability), of water (acid catalysis), of halogens (formation of the halonium ion), of halogens in the presence of water (formation of halohydrins), of mercuric salts and water, and subsequent reduction (oxymercuration). Markovnikov's rule. Hydroboration-oxidation reaction. Hydroxylation of alkenes (formation of vicinal diols). Epoxide formation. Ozonolysis. Addition reactions on dienes. Electrophilic addition of hydrogen halides, halogens and water to the triple bond. Hydroboration-oxidation of alkynes. D4- Aliphatic nucleophilic substitution reactions. SN2 and SN1 reaction mechanisms and their competition. Kinetic equation, energy profile and sterochemical aspects involved in the two mechanisms. Amines, alcohols, thio alcohols, sulfides, phosphines as nucleophiles in aliphatic substitution reactions. Gabriel's synthesis of primary amines. Preparation of phosphonium salts. Alcohols, ethers, thioalkols, sulfides, alkyl sulfonates and epoxides as substrates able to undergo nucleophilic attack. Transformation of alcohols into alkyl halides and alkyl sulfonates by SN2 reactions. Synthesis of epoxides from aloidrine. Opening reactions of epoxides promoted by acidic or basic catalysis. D5- Elimination reactions performed on alkyl halides or alkyl quaternary ammonium salts. Mechanisms E1, E2 and E1cb. Energy profiles characterizing such mechanisms. Steric requirements for the E2 mechanism. Competition between the E1 and E2 mechanisms. Zaitsev' rule and Hofmann's rule. Competition between elimination and aliphatic nucleophilic substitution reactions. D6- Reactions of benzene and of substituted benzenes. Substitutions on the aromatic ring. Reactivity of benzene and its derivatives towards electrophilic and nucleophilic attack. Energy profiles of electrophilic and nucleophilic substitution reactions. Intermediate of Wheland and Meisenheimer in aromatic electrophilic and nucleophilic substitutions, respectively. Electrophilic aromatic substitutions: halogenation, nitration, sulfonation, alkylation and acylation (Friedel-Crafts) reactions of the benzene molecule. Reduction of anilines to nitrobenzenes carbonyl functions by means of the Clemmensen and Wolff-Kishner reactions. Inductive and mesomeric effects of groups linked to the benzene ring: their ability to modulate the reactivity of the aromatic ring and to orient the position of substitution. Preparations of diazonium salts (diazotation of primary amines) and their subsequent useful transformations in new benzene derivatives (reactions of arendiazonio salts). Aromatic nucleophilic substitution reactions governed by addition-elimination or addition-elimination mechanisms. D7- Reactions involving the carbonyl function as an electrophilic site. Acylic nucleophilic substitution reactions, reactivity scale of carboxylic acid derivatives (acyl halides, anhydrides, esters, carboxylic acids, amides) and their typical reactions. Transformation of carboxylic acids into acyl halides. Hydrolysis of nitriles. Nucleophilic addition on aldehydes and ketones. Use of Grignard reagents and metal hydrides. Nucleophilic-addition/elimination reactions involving nitrogen nucleophiles: formation of imines, enamines, hydrazones and semicarbazones. Nucleophilic-addition/elimination reactions involving oxygen or sulphur nucleophiles: formation of hydrates of aldehydes and ketones, ketals, acetals, thioketals and thioacetals. Reaction of aldehydes and ketones with phosphorus ylides: the Wittig reaction. Stereochemical implications in carbonyl additions. Nucleophilic additions to alpha-beta unsaturated carbonyl compounds. The Cannizzaro reaction. D8- Reactions involving the removal of hydrogens linked to carbon atoms alpha with respect to carbonyl. Halogenation of aldehydes and ketones (mechanism catalyzed by both acids and bases) and of carboxylic acids (Hell-Volhard-Zelinski reaction). Formation of enolate ions from carbonyl compounds. The addition reaction of Michael to alpha-beta unsaturated carbonyl compounds. The aldol addition and aldol condensation reactions. Robinson annulation. Claisen condensation. Decarboxylation of 3-oxocarboxylic acids. Acetacetic and malonic synthesis. D9- Pericyclic reactions: Diels-Alder reaction and sigmatropic transpositions (outline) D10- Reduction and oxidation reactions of functional groups (overview). E- Natural polyfunctional compounds of biological relevance. E1- Carbohydrates: classification and structure of monosaccharides, oligosaccharides (outlines) and polysaccharides (outline). Sub-classification of monosaccharides in aldoses and ketoses. Characterization of their stereochemistry through use of absolute (R/S) and relative (D/L) descriptors of configuration (relation with D and L glyceraldehyde). Epimerization of alpha-carbon of aldoses for establishment of tautomeric equilibria in basic aqueous media. Typical oxidation reactions of aldoses (formation of aldonic, aldaric and uronic acids, reaction with Br2, HNO3, Tollens and Fehlings reactives, periodic acid) and reduction of monosaccharides (formation of alditols). Reactions with phenylhydrazine (formation of phenylhydrazones and osazones). Ascending synthesis of Kiliani-Fischer. Ruff degradation. Furanose and pyranose hemiacetal cyclic forms, formation of alpha and beta anomers, mutarotation. Representation of hemiacetal forms by Haworth projections. O- and N-glycosides formation. E2- Amino acids: Structure, nomenclature, physical properties, acid-base properties. Zwitterionic form and isoelectric point. Alpha natural amino acids, chirality and use of descriptors of absolute (R/S) and relative (D/L) configuration. Examples of synthesis of alpha-amino acids: a) amination of alpha-halogen acids; b) reductive amination of alpha-ketoacids; c) Strecker's synthesis. Peptides and proteins structure (outline). Characteristics of the peptide bond. Convention in writing polypeptide chains. E3- Triglycerides: structure; saponification reaction.

Required knowledge: periodic table structure, electronic configuration and electronegativity of elements; main types of chemical bonds, ibridation, resonance structures; Broensted and Lewis acids and bases; organic functional groups, polarity, basic and acid behaviour, electrophilicity and nucleophilicity; organic functional classes, IUPAC nomenclature, physico-chemical features and reactivity; main types of organic reactions (additions, substitution, etc.) and their mechanisms; organic synthetic reactions; stereochemistry basics (enantiomers amd diastereoisomers, racemic mixtures, Cahn-Ingold-Prelog rules).

Wade, L. G. Jr. Organic Chemistry. 6th ed. Upper Saddle River, NJ: Pearson Prentice Hall; 2006. ISBN 0-13-147871-0.

Attendance at the course is mandatory.

The acquisition of CFUs for the course requires passing the final exam, held during the exam sessions published on Infostud. There are no midterm exams for partial exemption. The final exam consists of a written test which is preliminary to the oral examination. The written test assesses the student's ability to apply the principles of structure and reactivity of organic compounds to problem-solving.To access the written exam, students must register on the E-learning platform. The written test lasts only one session namely January/February, June/July, September, and November. The oral exam evaluates the student's preparation on the entire syllabus, clarity of presentation, and ability to connect and critically reason about the various topics covered in class. To achieve a score of 30/30 cum laude, the student must demonstrate that he has acquired an excellent knowledge of all the topics covered during the course, showing a natural ability to link between them quickly. To access the oral exam, students must register on INFOSTUD.

The course (10 CFU) is provided through traditional lessons integrated with exercises. The lessons are held in classrooms where there are devices suitable for projecting the slides of the course, available to Pharmacy students on the Sapienza E-learning platform. The exercises, provided throughout the course, cover all the topics covered during the theoretical lessons and prepare students for the written test. There are several summarizing sessions in which different quiz that are representative of those given to the exam, are shown.