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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
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== imine is an unusual primary ketimine that is readily isolable. 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+ [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.
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: : If nearby functional groups stabilize negative charge on the carbon atom, then imines can add carbanion equivalents at the nitrogen, e.g.: :(NC)2C=NR + R'Li → (NC)2C(Li)NRR' :MeN=
C(CH2)2C6H4 + RLi → MeRN
C9H8Li
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. The
asymmetric reduction of imines has been achieved by
hydrosilylation using a rhodium-
DIOP catalyst. Many systems have since been investigated. 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.
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 (
polyimines) 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.
Miscellaneous reactions Akin to
pinacol couplings, imines are susceptible to reductive coupling leading to 1,2-
diamines. Imine are oxidized with
meta-chloroperoxybenzoic acid (mCPBA) to give an
oxaziridines. 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 ==Biological role==