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