An imine (// or //) is a functional group or chemical compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen (H) or an organic group (R). If this group is not a hydrogen atom, then the compound can sometimes be referred to as a Schiff base. The carbon atom has two additional single bonds. The term "imine" was coined in 1883 by the German chemist Albert Ladenburg.
Nomenclature and classification
Usually imines refer to compounds with the connectivity R2C=NR, as discussed below. In the older literature, imine refers to the aza analogue of an epoxide. Thus, ethyleneimine is the three-membered ring species C2H4NH. The relationship of imines to amines having double and single bonds carries over to imides and amides, as in acetamide vs succinimide.
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. Imines exhibit diverse reactivity and are commonly encountered throughout chemistry. 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 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 is called a primary ketimine; a secondary imine with such groups is called a secondary ketimine.
- Primary aldimine
- Secondary aldimine
- Primary ketimine
- Secondary ketimine
- Aziridine and its derivatives are sometimes referred to as imines.
One way of naming aldimines is to take the name of the radical, remove final "e", and add "-imine", for example ethanimine. Alternately, an imine is named as a derivative of a carbonyl, adding the word "imine" to the name of a carbonyl compound whose oxo group is replaced by an imino group, for example sydnone imine and acetone imine (an intermediate in the synthesis of acetone azine).
N-Sulfinyl imines are a special class of imines having a sulfinyl group attached to the nitrogen atom.
An iminium cation is a related functional group in which the nitrogen has a fourth bond, giving it a positive charge.
|common usage||butyraldehyde imine||acetaldehyde N-methylimine|
- by replacing the final -e of the parent hydride, R–CH3, with the suffix "-imine";
- as alkylidene derivatives of azane;
- (rare) as alkylidene derivatives of "amine".
An obsolete nomenclature treats aldimines as derivatives of a parent aldehyde.
Synthesis of imines
Imines are typically prepared by the condensation of primary amines and aldehydes and less commonly ketones. In terms of mechanism, such reactions proceed via the nucleophilic addition giving a hemiaminal -C(OH)(NHR)- 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 push the reaction in 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.
More specialized methods
Several other methods exist for the synthesis of imines.
- Reaction of organic azides with metal carbenoids (produced from diazocarbonyl compounds).
- Condensation of carbon acids with nitroso compounds.
- The rearrangement of trityl N-haloamines in the Stieglitz rearrangement.
- Dehydration of hemiaminals.
- 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.
- Primary ketimines can be synthesized via a Grignard reaction with a nitrile.
Imines participate in many reactions that are analogous to the reactions of aldehydes and ketones:
- An imine is reduced in reductive amination.
- An imine reacts with an amine to an aminal, see for example the synthesis of cucurbituril.
- An imine reacts with dienes in the Imine Diels-Alder reaction to a tetrahydropyridine.
Precursors to heterocycles
Unhindered imines tend to oligomerize. This behavior is common for imines derived from formaldehyde, such as CH3N=CH2, which trimerizes to the hexahydrotriazine.
Imines are widely used as intermediates in the synthesis of heterocycles. Aromatic imines reacts with an enol ether to a quinoline in the Povarov reaction. The C=N bond in imines is reactive toward cycloadditions. Imines react, thermally, with ketenes in [2+2] cycloadditions to form β-lactams in the Staudinger synthesis. An imine can be oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an oxaziridine
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. Imine react with dialkylphosphite in the Pudovik reaction and Kabachnik–Fields reaction
Somewhat like the parent amines, imines are mildly basic and reversibly protonate to give iminium salts. Iminium derivatives are particularly susceptible to reduction to the amines using transfer hydrogenation or by the stoichiometric action of sodium cyanoborohydride. Since imines derived from unsymmetrical ketones are prochiral, their reduction is a useful method for the synthesis of chiral amines.
Other reducing agents are lithium aluminium hydride and sodium borohydride.
The first asymmetric imine reduction was reported 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. Many systems have since been investigated.
Imine polymers (polyimines) can be synthesised from multivalent aldehydes and amines. This polymerisation reaction is feasible because it generally proceeds immediately when mixing the relevant components. Also, because no additional chemicals are required and the only formed side product is water, this reaction is very environmentally friendly. Polyimines are particularly interesting materials because of their application as vitrimers. They are known to be easily recyclable and self-healing.
- Schiff base
- Other functional groups with a CN double bond: oximes, hydrazones
- Other functional groups with a CN triple bond: nitriles, isonitriles
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