ORGANIC CHEMISTRY II M - Z

Learning Objectives

• MODULO 1

  The course aims to provide students with a more in-depth training in Organic Chemistry from the first basic course, particularly with regard to nomenclature, chemical properties and reactivity of multifunctional compounds; the main classes of organic compounds of biological significance: carbohydrates, amino acids and peptides, lipids; the major heterocyclic systems. Students will gain further knowledge on advanced organic synthesis reactions, learning to develop simple synthetic sequences of polyfunctional organic compounds and to apply the principles of modern synthetic strategies for disconnection approaches, formation of carbon-carbon bonds, deprotection protection of functional groups.

• MODULO 2

  Acquire experiences on the methodologies and techniques on the organic synthesis through the preparation of some products and their identification.

Course Structure

• MODULO 1

  The teaching will take place through the discussion of the various topics reported in the program and will include days dedicated to the clarification of doubts and the simulation of the oral exam.

• MODULO 2

  Frontal lessons.

  Laboratory exercises. Use of spectroscopies for the characterization of organic compounds (UV-Vis, IR, ¹H- , ¹³C-NMR).

Detailed Course Content

• MODULO 1

  Enols, Enolates, enamines

  Keto-enol tautomerism –Enolization catalysed by acids and bases – Enols stability - Acidity of a-hydrogens of carbonyl compounds – Enolate ions – Lithium enolates- Halogenation in a of carbonyl and carboxylic compounds –Haloform reaction –Alkylation of acarbons – Alkylation and acylation of acarbons by using enamines – The Aldol condensation: synthesis of b-hydroxyaldehydes – Dehydratation of aldols – Cross-condensation of aldols – The Claisen condensation: synthesis of -ketoesters – The Claisen ester condensation compared to the aldol condensation – Problems with acylation at carbon – Intramolecular Claisen ester and aldol condensations –Robinson annelation– b-ketoacids decarboxylation –Malonic synthesis –Acetoacetic synthesis

  a,b- unsatured carbonyl compounds

  Electron Delocalization and Resonance - Conjugation effects - Conjugate additions reactions – b-carbon alkylation – Michael reaction – Conjugate addition or direct addition to the carbonyl group - “hard” e “soft” nucleophiles - Conjugate addition of ammonia and amines– Conjugate addition of alcohols and thiols – Reactions with organometallic reagents – The Effect of the Cu(I) salts – Conjugate addition of enolates– Conjugate addition followed by cyclization in the ring synthesis

   

  Benzene and the aromatic compounds

  Linear and cyclic conjugated polyenes stability - Delocalized Electrons: the Structure of Benzene, the prototypic aromatic system - Identifying aromatic systems - Criteria for Aromaticity - Huckel's rule - Antiaromaticity- Aromatic polycyclic hydrocarbons - Nomenclature of Mono- and polysubstituted Benzenes - General Mechanism for Electrophilic Aromatic Substitution Reactions - Halogenation – Nitration - Sulfonation - Friedel–Crafts Acylation -Friedel–Crafts Alkylation of Benzene -Alkylation of Benzene by Acylation - Reduction - Reactions at the side chain - The Effect of Substituents on Reactivity - Inductive and Resonance Electron Donation and Withdrawal- Relative Reactivity of Substituted Benzenes - The Effect of Substituents on Orientation –The Ortho–Para Ratio– Chloromethylation-The Gattermann-Koch , the Gattermann , the Vilsmeyer , the Reimer-Tiemann formylation.

  Aryl Halides

  Nomenclature - Chemical properties compared to alkylic, vinylic and alleli alides- Nucleophilic Aromatic Substitution Reaction – The addition-elimination mechanism (S_NAr) - The elimination-addition mechanism (SNEA)- The benzyne

  Phenols

  Nomenclature – Physical and chemical properties – Preparation from aryl halides and from aryl diazonium salts – Acidity – Electrophilic aromatic substitution - Hydroxymethylation reaction- Phenolic resins- The Kolbe reaction – The Lepetit-Bucherer reaction– Polyphenols – Oxidation -
  Quinone-hydroquinone redox equilibrium – Natural antioxydants – Phenolic ethers – The Claisen rearrangement

   

  Amines and their derivatives

  Alkyl- and arylamines classification and nomenclature – Arylamines: structure and physical properties - Acidity and basicity– Enantiomeric pyramidal inversion – Quaternary armonium salts (properties, stereochemistry) - Synthesis of amines (alkylation, reducive amination, reduction of azides, nitriles, amides and nitro compounds, the Hofmann rearrangment , the Mannich reaction, the Hofmanndegradation – the Gabrielsynthesis – Preparation of arylamines – Reactions with carbonyl compounds – Reactions with nitrous acid - Imines, enamines – Diazoniun salts and their coupling reactions – Diazonium salts replacement reactions.

   

  Sulfur compounds

  Thiols : structure, nomenclature, physical properties – Acidity - Preparation reactions – oxydation reactions– Sulfides – Disulfides - Solfinic and Solfonic acids

   

  Heterocyclic compounds

  The Hantzsch-Widman nomenclature – The replacement nomenclature - Common nomenclature - Synthesis reactions –Retrosynthetic analysis – Cyclization reactions - The Baldwin rules– Arylnitrene ring-expansion and ring-contraction– Modern synthetic methods (combinatorial synthesis , microwaves assisted synthesis).

   

  Aromatic heterocycles
  Heteroaromaticity – Five- and six membered aromatic heterocyclic rings - Furan, pyrrole, thiophene, pyridine. Synthesis starting from 1,3 and 1,4-dicarbonylic compounds – Heteroaromatic rings with two o more heteroatoms- Benzo-fused heterocycles- Electrophilic Aromatic Substitution Reactions, Nucleophilic Aromatic Substitution Reactions, oxidations, reductions –Pyridine N-oxyde.

   

  Carbohydrates

  Classification of Carbohydrates - The D and L Notation - Configurations of Aldoses and Ketoses - Redox Reactions of Monosaccharides – Oxidation - Chain Elongation: the Kiliani–Fischer Synthesis -

  Chain Shortening: the Wohl and Ruff Degradation- Cyclic Structure of Monosaccharides: Hemiacetal Formation - Acylation and Alkylation of Monosaccharides -Formation of Glycosides - The Anomeric Effect - Reducing and Nonreducing Sugars – Mutarotation – Disaccharides - Polysaccharides

  Solar energy, photosynthesis and the flow to Living Organisms- Some Eco Friendly Products Derived from cellulose fermentation

   

  Lipids

  Fatty Acids- Fats and Oils – Waxes – Triglycerides – Saponification –Micelles - detergent properties- Soaps and detergents - Prostaglandins – Steroids – Terpenes – Phospholipids –Phospholipid bilayers assembly- Liposomes - Cell membrane – Lecithins –Sphingolipids – Fat soluble vitamis

• MODULO 2

  • Introductive ideas on common identification techniques as: ¹H - e ¹³C-NMR, UV-Vis, GC, GC/MS e HPLC.

    Practical execution of electrophilic aromatic substitution, carbonyl addition-elimination reactions, local anesthetic multistage synthesis.

    Isolation, purification and characterization of the products obtained in the experiences through: : p.f., UV-Vis, IR, ¹H- e ¹³C-NMR.

     

Textbook Information

• MODULO 1

  • Required Texts

    § W.H.Brown, B.L.Iverson, E.V.Anslyn, C.S.Foote, CHIMICA ORGANICA, Edises 2015

    § D. Sica, F. Zollo, CHIMICA DEI COMPOSTI ETEROCICLICI, Edises 2011

    § Notes

    Recommended Readings:

    § P.Y.Bruice, CHIMICA ORGANICA, Edises 2012

    § J. Claiden, N. Greeves, S. Warren, ORGANIC CHEMISTRY, Oxford University Press 2012

• MODULO 2

  1. D.L. Pavia, G.M. Lampman, G.S. Kritz, Introduction to Organic Laboratory, Saunder College Pubblishing.

  2. R.M. Silverstein, F.X. Webster, Identificazione Spettroscopica di Composti Organici,

  Ambrosiana.