In organic chemistry, an imine ( or ) 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. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions. Distinction is sometimes made between aldimines and ketimines, derived from aldehydes and ketones, respectively.
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 double-bonded 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 amines and nitriles are 1.47 and 1.16 Å respectively. 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.
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 imides and amides, as in succinimide vs acetamide. Imines are related to ketones and aldehydes 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 imines are the Schiff amides of sulfinic acids. Azines are the di-imines produced from hydrazines.
Synthesis of imines
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 −C(OH)(NR2)− 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 molecular sieves 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.
From nitriles Primary ketimines can be synthesized via a Grignard reaction with a nitrile. This method is known as Moureu-Mignonac ketimine synthesis. 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)
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 iminophosphoranes and organic azides in an aza-Wittig reaction. 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.
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 ketenes in [2+2] cycloadditions to form β-lactams in the Staudinger synthesis. Several variants have been described. Imine react with dienes in the Imine Diels-Alder reaction to a tetrahydropyridine. tosylimines react with α,β-unsaturated carbonyl compound to give allylic amines in the Aza-Baylis–Hillman reaction.
Acid-base reactions Somewhat like the parent amines, imines are mildly basic and reversibly protonate to give iminium salts:
R2C=NR' + H+ ↽ − ⇀ {\displaystyle {\ce {<=>>}}} [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
Lewis acid-base reactions Imines are common ligands in coordination chemistry. Particularly popular examples are found with Schiff base ligands derived from salicylaldehyde, the salen ligands. 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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