Heterocycles | Organic Chemistry 3
Naming the Heterocycles
Heterocycle = ring compound containing at least 1 non-carbon atom in the ring.
A prefix is used according to this heteroatom: aza- (nitrogen), oxa- (oxygen), thia- (sulfur), phospha- (phosphorus).
The ring atoms are numbered starting with the heteroatom.
Other names are widely used for common molecules, especially for aromatic compound:
Reactivity of Nonaromatic Heterocycles
Heterocyclopropanes and heterocyclobutanes ⇒ high strain ⇒ reactive (ring opening)
Heterocyclopentanes and heterocyclohexanes ⇒ no strain ⇒ less reactive than their smaller-ring counterparts
Heterocyclobutanes are less reactive than heterocyclopropanes ⇒ heating generally needed
Aromatic Heterocyclopentadienes
butadiene + sp2 hybridized heteroatom bearing lone electron pair(s)
⇒ delocalized π electrons in an aromatic 6-electron framework
Aromaticity: furan < pyrrole < thiophene
Synthesis of Heterocyclopentadienes (Paal-Knorr Synthesis):
Aromatic Heterocyclopentadienes - Reactivity
Reactivity largely based on the chemistry of benzene (due to the aromaticity).
Electrophilic substitution:
Mechanism: electrophilic aromatic substitution frequently favored at C2
Ring opening:
Cycloaddition:
Mechanism: Diels-Alder reaction
Pyridine
Pyridine = Benzene derivative (sp2-hybridized nitrogen atom replaces a CH unit).
Properties: Aromatic but electron poor (due to the electronegativity of N).
Lone pair on nitrogen ⇒ weakly basic heterocycle.
Synthesis of Pyridine (Hantzsch Synthesis):
Steps of the synthesis:
Reactivity of Pyridine
Reactivity derives from:
- aromaticity (slow electrophilic substitution at C3)
- cyclic imine character (fast nucleophilic substitution at C2 or C4)
Electrophilic substitution:
Nucleophilic substitution:
- Chichibabin Reaction:
Mechanism: Addition-Elimination
- Other types of nucleophilic substitution:
