Imine

In organic chemistry, an imine (/ɪˈmiːn/ or /ˈɪmɪn/) is a functional group or organic compound containing a carbon–nitrogen double bond (C=N). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds.^[1][2] Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.^[3]

Structure

For ketimines and aldimines, respectively, the five core atoms (C₂C=NX and C(H)C=NX, X = H or C) are coplanar. Planarity results from the sp²-hybridization of the mutually

The term "imine" was coined in 1883 by the German chemist Albert Ladenburg.^[6]

Usually imines refer to compounds with the general formula R₂C=NR, as discussed below.^[7] In the older literature, imine refers to the aza-analogue of an epoxide. Thus, ethylenimine is the three-membered ring species aziridine C₂H₄NH.^[8] The relationship of imines to amines having double and single bonds can be correlated with imides and amides, as in succinimide vs acetamide.

Imines are related to

A primary imine in which C is attached to both a hydrocarbyl and a H is called a primary aldimine; a secondary imine with such groups is called a secondary aldimine.[10] A primary imine in which C is attached to two hydrocarbyls is called a primary ketimine; a secondary imine with such groups is called a secondary ketimine.^[11]

• 
  Primary aldimine,

  E-isomer
• 
  Secondary aldimine, E-isomer
• 
  Primary ketimine
• 
  Secondary ketimine
• 
  Aziridine and its derivatives are sometimes referred to as imines.

Synthesis of imines

Carbonyl-amine condensation

Imines are typically prepared by the condensation of primary amines and aldehydes.

Rarer than primary amines is the use of ammonia to give a primary imine.[17] In the case of hexafluoroacetone, the hemiaminal intermediate can be isolated.^[18]

From nitriles

• Reaction of organic azides with metal carbenoids (produced from diazocarbonyl compounds).[23]
• Condensation of
  carbon acids with nitroso
  compounds.
• The rearrangement of trityl N-haloamines in the Stieglitz rearrangement.
• 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.
• Multicomponent synthesis of 3-thiazolines in the Asinger reaction.
• Thermal decomposition of oximes.^[24]

Reactions

Hydrolysis

The chief reaction of imines, often undesirable, is their hydrolysis back to the amine and the carbonyl precursor.

R₂C=NR' + H₂O ⇌ R₂C=O + R'NH₂

Precursors to heterocycles

Imines are widely used as intermediates in the synthesis of heterocycles.

• Aromatic imines react with an enol ether to a quinoline in the Povarov reaction.
• Imines react, thermally, with
  β-lactams in the Staudinger synthesis.^[25] Several variants have been described.^[26][27]
• Imine react with dienes in the Imine Diels-Alder reaction to a tetrahydropyridine.
• allylic amines in the Aza-Baylis–Hillman reaction
  .

Alternatively, primary imines are sufficiently acidic to allow N-alkylation, as illustrated with benzophenone imine:^[28]

(C₆H₅)₂C=NH + CH₃Li → (C₆H₅)₂C=NLi + CH₄

(C₆H₅)₂C=NLi + CH₃I → (C₆H₅)₂C=NCH₃ + LiI

Lewis acid-base reactions

Imines are common

Very analogous to ketones and aldehydes, primary imines are susceptible to attack by carbanion equivalents. The method allow for the synthesis of secondary amines:[29]^[30]

R₂C=NR' + R"Li → R₂R"CN(Li)R'

R₂R"CN(Li)R' + H₂O → R₂R"CNHR' + LiOH

Imine reductions

Imines are reduced via reductive amination. An imine can be reduced to an amine via hydrogenation for example in a synthesis of m-tolylbenzylamine:^[31]

Other reducing agents are lithium aluminium hydride and sodium borohydride.^[32]

The

Unhindered aldimines tend to cyclize, as illustrated by the condensation of methylamine and formaldehyde, which gives the hexahydro-1,3,5-triazine.

Imine polymers (

Imine are oxidized with

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. Imine react with dialkylphosphite in the Pudovik reaction and Kabachnik–Fields reaction

Biological role

Imines are common in nature.^[40][41] The pyridoxal phosphate-dependent enzymes (PLP enzymes) catalyze myriad reactions involving aldimines (or Schiff bases).^[42] Cyclic imines are also substrates for many imine reductase enzymes.^[43]

See also

• Enamine
• Schiff base
• Carboximidate
• Oxazolidine
• Other functional groups with a C=N double bond:
  oximes, hydrazones
• Other functional groups with a C N triple bond:
  isonitriles