Heterocycles | Organic Chemistry 3
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:
