Heterocycles | Organic Chemistry 3

Heterocycles are studied in this chapter: reactivity of non-aromatic heterocycles, synthesis, properties and reactivity of aromatic heterocyclopentadienes, synthesis, properties and reactivity of pyridine

Nomenclature of Heterocycles

Heterocycles:

Ring compounds containing at least 1 non-carbon atom in the ring
 

Nomenclature:

A prefix depending on the heteroatom is used in front of the corresponding cycloalkane name: aza- (nitrogen), oxa- (oxygen), thia- (sulfur), phospha- (phosphorus). Atoms in the ring are numbered starting with the heteroatom
 

 

Other names are widely used for common molecules, especially for aromatic compounds:
 

Reactivity of Nonaromatic Heterocycles

Heterocyclopropanes and heterocyclobutanes: high strain ⇒ very reactive (ring opening). Heterocyclobutanes are less reactive than heterocyclopropanes ⇒ heating generally required:


Heterocyclopentanes and heterocyclohexanes: no strain ⇒ less reactive than their smaller-ring counterparts

Aromatic Heterocyclopentadienes

Aromatic heterocyclopentadienes consist of butadiene and sp2 hybridized heteroatom bearing lone electron pair(s) ⇒ π electrons are delocalized in an aromatic 6-electron framework

Aromaticity strength: furan < pyrrole < thiophene. Reactivity is inversely proportional to the aromaticity strength

 

 

Synthesis of heterocyclopentadienes (Paal-Knorr Synthesis):
 

Aromatic Heterocyclopentadienes - Reactivity

The reactivity of aromatic heterocyclopentadienes is 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 is a derivative of benzene: an sp2-hybridized nitrogen replaces a CH unit

Properties of pyridine: aromatic but electron poor due to the electronegativity of N. The lone pair on nitrogen makes pyridine weakly basic (pKb = 8.77)

 

 

Synthesis of Pyridine (Hantzsch Synthesis):

Steps of the synthesis:

Reactivity of Pyridine

The reactivity of pyridine derives from its aromaticity (slow electrophilic substitution in C3) and from its cyclic imine character (fast nucleophilic substitution in C2 or C4)


Electrophilic substitution:

 

Nucleophilic substitution:
 

- Chichibabin Reaction:


Mechanism: addition-elimination

 

- Other types of nucleophilic substitution: