Heterocycles | Organic Chemistry 3

The Heterocycles are studied in this chapter: the reactivity of nonaromatic heterocycles, the synthesis, properties and reactivity of aromatic heterocyclopentadienes, the synthesis, properties and reactivity of pyridine.

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: