imine

The general structure of an imine

"Ketimine" redirects here. It should not be confused with "Ketamine"

An imine is a functional group or chemical compound containing a carbon–nitrogen double bond ^[1]. Due to their diverse reactivity, imines are common substrates in a wide variety of transformations. An imine can be synthesised by the nucleophilic addition of an amine to a ketone or aldehyde giving a hemiaminal -C(OH)(NHR)- followed by an elimination of water to yield the imine. (see alkylimino-de-oxo-bisubstitution for a detailed mechanism) However, the equilibrium in this reaction usually lies in favor of the free carbonyl compound and amine, so that azeotrope distillation or use of a dehydrating agent such as molecular sieves is required to push the reaction in favor of imine formation.

Addition reactions with primary amines give imines that are stable under an inert atmosphere. In the presence of oxygen or water, such imines will quite readily hydrolyze or oligomerize. However, with an aryl group or certain stabilizing alkyl substituents on nitrogen, the imine formed is stable to oxygen and water and is called a Schiff base. In contrast, imine condensations using ammonia and a carbonyl compound do not lead to stable imines - the imine formed quickly oligomerizes such as in the reaction of formaldehyde and ammonia which gives hexamine instead of the corresponding imine. When a secondary amine is used, elimination of water from the hemiaminal leads to an iminium ion. This iminium ion can further react to form either an aminal, or enamine if there is an sp³-hybridized carbon in the alpha position. Addition of suitably activated carbonyl compounds to this imminium ion also leads to the corresponding Mannich base.

Imine synthesis

Several laboratory methods exist for the synthesis of imines.

• Condensation of amines with carbonyls in alkylimino-de-oxo-bisubstitution
• Condensation of carbon acids with nitroso compounds
• The rearrangement of trityl N-haloamines in the Stieglitz rearrangement
• Dehydration of hemiaminals ^[2]
• By reaction of alkenes with hydrazoic acid in the Schmidt reaction
• By reaction of a nitrile, hydrochloric acid and an arene in the Hoesch reaction

Imine reactions

• An imine can be hydrolysed with water to the corresponding amine and carbonyl compound.
• An imine reacts with an amine to an aminal, see for example the synthesis of cucurbituril.
• An imine reacts with dienes in the Aza Diels-Alder reaction to a tetrahydropyridine.
• An imine can be oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an oxaziridine
• An aromatic imine reacts with an enol ether to a quinoline in the Povarov reaction.
• A tosylimine reacts with an α,β-unsaturated carbonyl compound to an allylic amine in the Aza-Baylis-Hillman reaction.
• Imines are intermediates in the alkylation of amines with formic acid in the Eschweiler-Clarke reaction.
• A rearrangement in carbohydrate chemistry involving an imine is the Amadori rearrangement.
• A methylene transfer reaction of an imine by an unstabilised sulphonium ylide can give an aziridine system.
• An imine is an intermediate in reductive amination.

Imine reductions

An imine can be reduced to an amine via hydrogenation for example in a synthesis of m-tolylbenzylamine:^[3]

Other reducing agents are lithium aluminium hydride and sodium borohydride ^[4].

The first asymmetric imine reduction was performed in 1973 by Kagan using Ph(Me)C=NBn and PhSiH₂ in a hydrosilylation with chiral ligand DIOP and rhodium catalyst (RhCl(CH₂CH₂)₂)₂ ^[5]. Many systems have since been investigated ^[6]

Amidates

Imidates (also known as imino ethers) (R-N=C(OR)R) are imines with an oxygen atom connected to carbon. These compounds find use in organic synthesis as building blocks and intermediates for example in the Mumm rearrangement and the Overman rearrangement. An example of an imidate is benzyl 2,2,2-trichloroacetimidate used to protect an alcohol as a benzyl ether with release of trichloroacetamide.

Amidates are the corresponding amide enolates: R-N=C(O^-)R and find use as ligands.

See also

• Other functional groups with a CN double bond: oximes, hydrazones
• Other functional groups with a CN triple bond: nitriles, isonitriles

References