Course Program

Heterocyclic Chemistry syllabus

Part 1. Aromatic heterocycles: structures, properties, reactivity, occurrence and biological functions, applications

Introductory remarks, syllabus, learning outcomes,the course at a glance, classification of heterocyclic compounds, nomenclature, structures, naturally occurring heterocycles, the uniqueness of heterocyclic chemistry.

Aromatic heterocyclic compounds: structures, aromaticity, properties, reactivity

Five-membered heterocycles with one heteroatom: thiophene, furan, pyrrole: structures, general properties, reactivity, electrophilic aromatic substitution, regiochemistry and mechanisms, Diels-Alder, electrophilic addition, Adler porphyrin synthesis, reactions with bases, nucleophiles, metalation, polythiophenes and their applications.

Five-membered heterocycles with two heteroatoms: structure, properties, reactivity and applications of 1,3-azoles (oxazoles, thiazoles, imidazoles) and 1,2-azoles (isooxazoles, isothiazoles, pyrazoles)

Natural five-membered heterocycles and their derivatives: properties, structure, properties, biological roles of thiazoles (thiamine); porphyrins, chlorophylls, photosynthesis and artificial photosynthesis

Benzo-fused five-membered heterocycles: indole structure, properties, electrophilic aromatic substitution, Mannich, Vilsmeier reactions, gramine chemistry, metallation and alkylation reactions, naturally occurring indoles, indigo dyes, alkaloids

Six-membered heterocycles-pyridine: structure, properties aromatic electrophilic substitution, nucleophilic substitution, metallation, pyridine-N-oxides, oxypyridines, natural pyridines: nicotinamide, NAD(P)H, alkaloids, bipyridyl-based herbicides

Six-membered heterocycles with two heteroatoms-pyrimidines, pyridazines, pyrazines: structure, properties, reactions.

Benzo-fusedsix-membered heterocycles-quinoline, isoquinoline structures, properties, electrophilic substitution, side chain reactions, nucleophilic reactions. Pyrylium and flavylium cations: properties and reactivity, naturally-occurring benzo-fused six-membered heterocycles: quinolines, isoquinolines, purines, pterins, carbolines, isoalloxazines, flavones, anthocyanines: properties, reactivity

Part 2. Aromatic heterocycles: synthesis and biosynthesis

The synthesis of aromatic heterocyclic compounds: key reactions, general strategies. Heterocyclic synthesis in nature: overall view of biosynthetic pathways

Synthesis of furans, thiophenes, pyrroles, oxazoles, thiazoles, diazoles (imidazoles, pyrazoles), isooxazoles, isothiazoles. Synthesis of imidazoles and thiazoles in nature: histidine, thiamine, luciferins.

Indole synthesis: general strategies, Fischer, Reissert, Leimgruber–Batcho, Bartoli, Larock, Madelung, Gassman, Fukuyama, Baeyer-Emmeling, Nenitzescu, Hemetsberger. Indole biosynthesis: tryptophan, 5,6-dihydroxyindoles and melanin precursors.

Pyridine: synthesis from 1,5-diketo derivatives, Hantzsch, Guareschi. Pyridine synthesis in nature.

Pyrimidines, pyridazines, pyrazines: synthesis

Quinoline synthesis: general strategies, Skraup, Doebner- von Miller, Combes, Conrad-Limpach-Knorr, Friedlander.

Isoquinoline synthesisBischler-Napieralski, Pomeranz-Fritsch, Pictet-Spengler,

Flavone synthesis: Allan-Robinson and Baker-Venkataraman

Biosynthesisofbenzo-fused six-membered heterocycles: quinoline, isoquinoline, flavones and anthocyanidines

Purines-pteridines: synthesis and biosynthesis

Special seminars: applications of heterocyclic chemistry

Reviewing Lectures: overall recapitulation of concepts

 

Bibliographic references

 Comprehensive Heterocyclic Chemistry series, Editors-in-Chief: Alan R. Katritzky and Charles W. Rees

ExamOral exam

Prerequisites

 This course complements the basics of heterocyclic chemistry delivered in organic chemistry courses, and requires general concepts of organic synthesis, natural product chemistry and biochemistry. It focuses  on 5- and 6-membered heteroaromatic systems and their benzo-fused derivatives.

For each class of compounds it offers an overview of:

a) Structural features and their relationships with main physical and chemical properties;

b) Fundamental reactivity

c) Biological role and significance

d) Classic synthetic approaches

e) Biosynthetic pathways

f) Applications and general relevance.

 

Syntheses will be presented with a view to highlighting:

a)The strategy/tactics of ring constructionalso via retrosynthetic analysis

b)Key enabling reactions

c)Scope with respect to alternative approaches