ORGANIC CHEMISTRY II
AA 2009/10
Angelo Fontana
Educational goals. The aim of this course is to illustrate the mechanisms of the main organic reactions and the chemistry of heterocycles (structure, synthesis and reactivity). The student has learned previously the classification of individual organic compounds and their fundamental properties, while with this advanced course he will learn the rationale of the chemistry of organic compounds with an integrated approach. The culture of chemistry is essential and unavoidable for a pharmaceutical biotechnologist and attending to this course will be particularly useful also for other courses of the laurea in Pharmaceutical Biotechnologies (BioFarm).
Mechanisms of organic reactions. Reactive intermediates in organic chemistry. Carbocations, carbanions, carbenes and radicals. Aliphatic nucleophilic substitution. Mechanism and stereochemistry of SN2 and SN1 reactions. Examples of internal nucleophilic substitution (SNi). Elimination reactions. E1 and E2 mechanism. Aromatic electrophilic substitution. Effects of activation, deactivation and orientation of substituents in benzene derivatives. Reactions of nucleophilic aromatic substitution. Addition reactions. Addition to the double and triple carbon-carbon bond. Electrophilic addition. Markownikov rule and its exceptions. Radical and nucleophilic addition. Addition to polyenes. Addition to multiple carbon-heteroatom (O, S, N) bond. Rearrangement reactions. Reactions Hofmann, Curtius and Lossen. Claisen and benzidine rearrangement. Multi-functional compounds. Halogenated alkenes, alcohols, ketones and acids. Unsaturated alcohols. Carbonyl compounds (a-b unsaturated). Aldol condensation. Glycols. Dicarboxylic acids, ketoacids and ketoesters. Chemistry of acetoacetic acid derivatives. Exercises of organic synthesis.
Heterocyclic compounds. Types of hetero-atoms (N, O, S) and size of rings. Triatomic heterocycles. Synthesis and chemistry of ethylene oxide and ethylenimmine. Heterocycles with four and five atoms. Lactones and lactams. Structure of pyrrole. Acid-base properties. Electrophilic substitution reactions. Alkylation reactions, acylation, halogenation, nitration, nitrosation, sulfonation, Reimer-Tieman reaction, Mannich reaction and Gattermann reaction. Furan. Electrophilic substitution reactions. Diels-Alder reactions of furan. Synthesis of furan derivatives. Properties and synthesis of thiophene. Indole. Electrophilic substitution reactions in indole. Chemistry of 3-alkyl-indoles. Halogenation of indole derivatives. Benzofurane and benzothiofene. 1,3-Azoles. Imidazole derivatives. Bromination, alkylation and acylation. Structure and reactivity of thiazole and oxazole. Structure and reactivity of pyrazole, isoxazole and isotiazole. Benzimidazole and benzothiazole. Triazoles. Structure of pyridine. Acid-base properties. Reactions of N-alkylation, N-acylation and electrophilic substitution. Nucleophilic substitution reactions. Oxy-, amino- and alkyl-pyridines. Synthesis of pyridine and derivatives. Pyridine N-oxide. Quinoline and isoquinoline. Electrophilic substitution reactions. Nucleophilic substitution reactions. Synthesis of quinoline and isoquinoline. Skraup reaction. Diazines. Structure and reactivity of pyrimidine, pyrazine and pyridazine. Electrophilic and nucleophilic substitution reactions. Synthesis of pyrimidine and derivatives. Triazines. IUPAC Nomenclature of heterocyclic compounds. Heterocycles of biological and pharmaceutical interest. Exercises of synthesis and properties of heterocycles.
Textbooks. Essentially the course is based on lecture notes, but the following textbooks are recommended for consultation:
- R.T. Morrison and R.N. Boyd, Organic Chemistry, Ambrosiana, Milan
- E.A. Gould, Mechanism and Structure in Organic Chemistry, Holt, Rinehart and Winston, New York
- J. March, Advanced Organic Chemistry: Reaction Mechanism and Structure, McGraw-Hill, New York
Office hours. Monday to Friday by appointment (phone 049-827 6156, Email: angelo.fontana @ unipd.it)
Examination. The examination consists of two written tests on (1) Mechanisms of organic reactions and (2) Chemistry of heterocyclic compounds. The vote derives from the average of two votes, possibly combined with a short oral examination. A list of 30-40 questions (for each test) will be distributed in advance to students and written examinations will be based on answers to 5 questions selected from those previously distributed and discussed.
Examination committee. A. Fontana, P. Polverino de Laureto (B. Spolaore)
The regular attendance to the course is highly recommended, since the examination
will be based exactly on only what has been presented and discussedin the classroom.