Imine

 ( Functional Groups ) 

In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional .

Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.

(1970). 9780471669425, John Wiley & Sons. . ISBN 9780471669425

Distinction is sometimes made between aldimines and ketimines, derived from aldehydes and ketones, respectively.

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Structure In imines the five core atoms (C₂C=NX, ketimine; and C(H)C=NX, aldimine; X = H or C) are coplanar. Planarity results from the sp²-hybridization of the mutually carbon and the nitrogen atoms. The C=N distance is 1.29–1.31 Å for nonconjugated imines and 1.35 Å for conjugated imines. By contrast, C−N distances in and are 1.47 and 1.16 Å respectively.

C. Sandorfy (1970). 9780470771204, John Wiley & Sons. ISBN 9780470771204

Rotation about the C=N bond is slow. Using NMR spectroscopy, both E and Z isomers of aldimines have been detected. Owing to steric effects, the E isomer is favored.

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Nomenclature and classification The term "imine" was coined in 1883 by the German chemist Albert Ladenburg.

Usually imines refer to compounds with the general formula R₂C=NR, as discussed below.

In the older literature, imine refers to the aza-analogue of an epoxide. Thus, ethylenimine is the three-membered ring species aziridine C₂H₄NH. The relationship of imines to amines having double and single bonds can be correlated with imide and amide, as in succinimide vs acetamide.

Imines are related to and by replacement of the oxygen with an NR group. When R = H, the compound is a primary imine, when R is hydrocarbyl, the compound is a secondary imine. If this group is not a hydrogen atom, then the compound can sometimes be referred to as a Schiff base. When R³ is OH, the imine is called an oxime, and when R³ is NH₂ the imine is called a hydrazone.

A primary imine in which C is attached to both a hydrocarbyl and a H (derived from an aldehyde) is called a primary aldimine; a secondary imine with such groups is called a secondary aldimine. A primary imine in which C is attached to two hydrocarbyls (derived from a ketone) is called a primary ketimine; a secondary imine with such groups is called a secondary ketimine.

N-Sulfinyl Imine are the Schiff amides of .

are the di-imines produced from hydrazines.

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Synthesis of imines

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Carbonyl-amine condensation Imines are typically prepared by the condensation of primary amines and aldehydes. Ketones undergo similar reactions, but less commonly than aldehydes. In terms of mechanism, such reactions proceed via the nucleophilic addition giving a hemiaminal intermediate, followed by an elimination of water to yield the imine (see alkylimino-de-oxo-bisubstitution for a detailed mechanism). The equilibrium in this reaction usually favors the carbonyl compound and amine, so that azeotropic distillation or use of a dehydrating agent, such as or magnesium sulfate, is required to favor of imine formation. In recent years, several reagents such as Tris(2,2,2-trifluoroethyl)borate B(OCH₂CF₃)₃, pyrrolidine or titanium ethoxide Ti(OEt)₄ have been shown to catalyse imine formation.

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

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From nitriles Primary ketimines can be synthesized via a Grignard reaction with a nitrile. This method is known as Moureu-Mignonac ketimine synthesis.

(2010). 9780470638859, John Wiley & Sons, Inc.. ISBN 9780470638859

For example, benzophenone imine can also be synthesized by addition of phenylmagnesium bromide to benzonitrile followed by careful hydrolysis (lest the imine be hydrolyzed):

C₆H₅CN + C₆H₅MgBr → (C₆H₅)₂C=NMgBr

(C₆H₅)₂C=NMgBr + H₂O → (C₆H₅)₂C=NH + MgBr(OH)

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Specialized methods Several other methods exist for the synthesis of imines.

• Reaction of organic azides with metal carbenoids (produced from diazocarbonyl compounds).
• The reaction of Ylide and Organic azide in an aza-Wittig reaction.
• Condensation of with nitroso compounds.
• The rearrangement of trityl N-haloamines in the Stieglitz rearrangement.
• By reaction of 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 .

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Reactions

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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

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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 ketenes in 2+2 cycloadditions to form β-lactams in the Staudinger synthesis. Several variants have been described.
• Imine react with in the Imine Diels-Alder reaction to a tetrahydropyridine.
• react with α,β-unsaturated carbonyl compound to give in the Aza-Baylis–Hillman reaction.

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Acid-base reactions Somewhat like the parent amines, imines are mildly basic and reversibly protonate to give iminium salts:

R₂C=NR' + H⁺ R₂C=NHR'⁺

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

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

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

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Lewis acid-base reactions Imines are common in coordination chemistry. Particularly popular examples are found with Schiff base ligands derived from salicylaldehyde, the . Metal-catalyzed reactions of imines proceed through such complexes. In classical coordination complexes, imines bind metals through nitrogen. For low-valent metals, η²-imine ligands are observed.

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Nucleophilic additions Very analogous to ketones and aldehydes, primary imines are susceptible to attack by carbanion equivalents. The method allows for the synthesis of secondary amines:

R₂C=NR' + R"Li → R₂R"CN(Li)R'

R₂R"CN(Li)R' + H₂O → R₂R"CNHR' + LiOH

This can be expanded to include carbons in the Mannich reaction, which is a straightforward and commonly used approach for producing β-amino-carbonyl compounds.

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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:

Other reducing agents are lithium aluminium hydride and sodium borohydride.For example:

The asymmetric reduction of imines has been achieved by hydrosilylation using a rhodium-DIOP catalyst. Many systems have since been investigated.J. Martens: Reduction of Imino Groups (C=N) in (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann) Houben-Weyl Stereoselective Synthesis, Workbench Edition E21 Volume 7, S. 4199-4238, Thieme Verlag Stuttgart, 1996, .

Owing to their enhanced electrophilicity, iminium derivatives are particularly susceptible to reduction to the amines. Such reductions can be achieved by transfer hydrogenation or by the stoichiometric action of sodium cyanoborohydride. Since imines derived from unsymmetrical ketones are prochiral, their reduction defines a route to chiral amines.

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

Imine polymers (polyimine) can be synthesised from multivalent aldehydes and amines. The polymerisation reaction proceeds directly when the aldehyde and amine monomers are mixed together at room temperature. In most cases, (small) amounts of solvent may still be required. Polyimines are particularly interesting materials because of their application as vitrimers. Owing to the dynamic covalent nature of the imine bonds, polyimines can be recycled relatively easily. Furthermore, polyimines are known for their self-healing behaviour.

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Miscellaneous reactions Akin to , imines are susceptible to reductive coupling leading to 1,2-.

Imine are oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an .

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 aziridines system. Imine react with phosphite ester in the Pudovik reaction and Kabachnik–Fields reaction

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Biological role Imines are common in nature. The pyridoxal phosphate-dependent enzymes (PLP enzymes) catalyze myriad reactions involving aldimines (or Schiff bases). Cyclic imines are also substrates for many imine reductase enzymes.

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See also

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

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