Organic Chemistry II (N110005SIS)
|Lecture ||Exercise ||Laboratory ||Examination
|3 ||2 ||0 ||Z+Zk
This course is continuation of Organic chemistry I. The course of Organic chemistry II is based on the description of organic reactions according to the mechanistic principles. It also includes chemistry of natural compounds (carbohydrates, amino acids, peptides, nucleic acids) as well as the fundamentals of the transition metal catalysis.
- 1. Organic reactions. Basic classification (addition, substitution, elimination), oxidation and reduction in organic chemistry, oxidation numbers, classification of reagents, the ways of the splitting of chemical bond, reaction mechanism, reaction intermediates, the theory of transition state, reaction coordinate, DG a DG# and their influence on the reaction rate and on the reaction equilibrium.
- 2. Nucleophilic substitution on saturated carbon atom. Mechanism and stereochemistry and their dependence on the structure of substrate, leaving group and solvent. Competitive reactions. Preparation of alcohols, ethers, thiols, esters, alkylation of ammonia and amines. Gabriel synthesis of amines, preparation of alkylhalides from alcohols using hydrogen halides or halides of inorganic acids, transformation of alcohols to the sulfonates (methanesulfonates and tosylates), sulfonates as the leaving groups, cleavage of ethers, opening of an epoxide ring. Formation of C-C bond by alkylation reactions - preparation of nitriles, reaction of organocooper reagents with alkyl-, alkenyl- and arylhalides.
- 3. Elimination reactions. E1 and E2 mechanism, relation to the nucleophilic substitution, dehydrohalogenation, Zaitsev's rule, influence of the bulkiness of the base, stereochemistry of the elimination reactions, Hofmann elimination, dehalogenation, dehydration, elimination during the solvolysis (E1), formation of alkynes, nitriles from dehydration of aldoximes, pinakol and Beckman rearrangements.
- 4. Nucleophilic addition to unsaturated carbon atom. Hydration of carbonyl group in aldehydes and ketones, acetals and ketals (revision). Addition of ammonia, amines, hydroxylamine and hydrazine to the carbonyl group of aldehydes and ketones. Cyanohydrines and aminonitriles. Reactions involving alpha-hydrogen: Acid and base catalyzed enolization, stability of enols, -halogenation of aldehydes and ketones, haloform reaction, consequences of enolization (exchange of alpha-hydrogen atoms with solvent, racemization of chiral centre on the alpha-carbon atom, aldolization of aldehydes , aldol condensation of ketones, mixed aldol condensation, alkylation of enolates). Reduction of aldehydes and ketones (revision), reductive amination, Wittig reaction. Conjugate addition to alpha,beta-unsaturated carbonyl compounds - addition of hydrogen halides, alcohols, thiols and amines, Michael addition, addition of organocooper reagents.
- 5. Nucleophilic substitution on the unsaturated carbon atom. Revision of the transformations of functional derivatives of carboxylic acids (acylhalides, esters, anhydrides), lactones and lactames. Claisen condensation, mixed Claisen condensation, condensation of esters with ketones, Dieckmann condensation. Malonic ester synthesis and acetoacetic ester synthesis.
- 6. Amides of carboxylic acids - Hofmann rearrangement, heterocumulenes (isocyanates, ketenes) and addition of nucleophiles on them. Reaction of functional derivatives of carboxylic acids with organometallic compounds. Reduction of functional derivatives of carboxylic acids using complex hydrides. Hydrolysis of functional derivatives of carboxylic acids, hydrolysis of nitriles - synthesis of carboxylic-, amino- and hydroxy acids.
- 7. Nucleophilic substitution on aromatic compounds. Preparation and reactivity of aromatic diazonium salts, their use in organic synthesis. Aromatic nucleophilic substitution (addition-elimination and elimination-addition mechanism).
- 8. Electrophilic addition to unsaturated systems. Addition of hydrogen halides to alkenes and alkynes, hydration of alkenes and alkynes (revision and extension), hydroboration, hydroboration/oxidation, addition of halogens, formation of halohydrines, epoxidation, dihydroxylation and ozonolysis of alkenes. Carbenes and cyclopropanation including Simmons-Smith reaction.
- 9. Electrophylic substitution on unsaturated carbon atom. Aromatic electrophilic substitution - introduction of second substituent (mechanism), comparison of benzene, naphthalene, pyrrole, furan, thiophene and pyridine. Claisen and Fries rearrangement.
- 10. Radical reactions. Formation of radicals, structure and stability of radicals. Radical halogenation of alkanes and its selektivity, Halogenation to allylic and benzyl position. Radical addition of HBr (revision) and RSH to alkenes.
- 11. Oxidation and reduction (revision and extension). Oxidation - oxidation of side chain on the aromatic ring, alcohols, spliting of 1,2-diols with HIO4, quinones. Oxidation of sulphur compounds and amines, Bayer-Villiger oxidation. Reduction - Birch reduction, reduction of alkynes to alkenes. Reduction of aldehydes and ketones (Wolff-Kižněr, Clemmensen, reductive dimerization - pinacol reaction, acyloin condensation). Reduction of nitrogen and sulphur derivatives (nitro compounds, disulfides, sulfonic acids).
- 12. Amino acids and peptides. Classification of amino acids, coded amino acids, structural types of coded amino acids, acido-basic equilibrium, isoelectric point, synthesis (Strecker synthesis, alkylation of acetamidomalonate). Chemistry of amino acids - behavior of andamino acids on heating, esters of amino acids, acylation of amino acids. Analysis of peptides - amino acid analysis, sequence analysis (Sanger's reagent, dansylation, Edman degradation). Synthesis of peptides - protective groups (Z, Boc, benzyl and t-butyl ester), formation of peptide bond (DCCI, solid phase synthesis).
- 13. Carbohydrates. Structure, stereochemistry, configuration, cyclic forms, mutarotation, oxidation and formation of lactones, reduction and epimerization of carbohydrates, glycosides. Disaccharides - reducing and non-reducing, polysaccharides (starch, cellulose).
- 14. Transition metals in organic chemistry. Basic principles - oxidation state, d-electron configuration, 18-electron rule, coordination-saturated and unsaturated complexes, the most common ligands, "electron book keeping", reactions in coordination sphere of transition metals (substitution of ligands, oxidative-addition/reductive-elimination, insertion/-elimination, transmetallation), example of catalytic cycle (cross-coupling reaction). Examples of important catalytic reactions (homogeneous catalytic hydrogenation, carbonylation of methanol, polymerization of alkenes, hydration of alkenes - Wacker process, alkene metathesis).