Jump to content

User:Benjah-bmm27/degree/3/KIBM

From Wikipedia, the free encyclopedia

Heterocycles, KIBM

[edit]

Azoles

[edit]

Reactivity

[edit]
  • 1,3-azoles tend to undergo clean electrophilic substitution at C5, but are less reactive than pyrrole
  • 1,2-azoles generally undergo electrophilic substitution at C4

Synthesis

[edit]

Anion chemistry

[edit]

Indoles

[edit]

Reactions of indoles

[edit]

Indole syntheses

[edit]

Carbazoles

[edit]

Benzofurans

[edit]

Reactions of benzofurans

[edit]
  • Benzofurans differ from indoles in that they tend to undergo electrophilic substitution in the 2 position, rather than the 3 position
    • This is probably because furan is far less aromatic than pyrrole, so the benzene ring of a benzofuran has more influence on the substitution pattern
  • Vilsmeier reaction, nitration and lithiation at occur at the 2 position
  • With bromine, benzofurans undergo electrophilic addition across the furan double bond - suggesting less aromaticity than indole

Benzofuran syntheses

[edit]
  • O-Aryl hydroxylamines react with ketones to give O-aryl ketoximes, which cyclize and dehydrate in acid to benzofurans, by a mechanism analogous to that of the Fischer indole synthesis
  • Sodium phenoxides react with α-bromoketones to give α-phenoxyketones, which cyclize and dehydrate in acid to benzofurans. This is the oxygen equivalent of the Bischler indole synthesis.

Quinolines and isoquinolines

[edit]
  • Quinoline
  • Isoquinoline
  • Both π deficient heterocycles
  • Their physical properties and chemical reactivity are very similar, but their syntheses are very different

Reactions of quinolines and isoquinolines

[edit]

Electrophilic aromatic substitution

[edit]
  • Quinoline undergoes nitration and bromination in the 5 and 8 positions (1:1 mixture of isomers)
  • Isoquinoline is more selective and only the 5 position is substituted

Nucleophilic substitution

[edit]

Anion chemistry

[edit]
  • 2-alkylquinolines have an acidic proton that can be removed by BuLi, forming an aza enolate that reacts with electrophiles

Reduction

[edit]
  • There are a number of important dihydroquinoline and tetrahydroquinoline drugs, so reduction of quinolines is industrially important
  • Lithium aluminium hydride reduces quinolines to dihydroquinolines, formally adding H2 across the N=C2 double bond
  • H2/Pt reduces the pyridine ring, leaving the benzene ring intact, thereby forming the tetrahydroquinoline
  • H2/Pd in concentrated hydrochloric acid reduces only the benzene ring, leaving the pyridine ring untouched
    • HCl must protonate the nitrogen sp2 lone pair, somehow deactivating the pyridine ring to hydrogenation.

Quinoline syntheses

[edit]

Isoquinoline syntheses

[edit]

Others

[edit]

Quiz

[edit]