Imine
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In
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clay ...
, an imine ( or ) is a
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the res ...
or
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
containing a
carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes ...
–
nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at seve ...
double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
(). The nitrogen atom can be attached to a
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
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.


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 double-bonded carbon and the nitrogen atoms. The C=N distance is 1.29-1.31 Ã… for nonconjugated imines and 1.35 Ã… for conjugated imines. By contrast, C-N distances in
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
s and nitriles are 1.47 and 1.16 Ã…, respectively. Rotation about the C=N bond is slow. Using
NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
, 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 In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...
. 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 Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound Dimethylacetamide, ...
. Imines are related to
ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...
s and
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...
s 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 In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...
. 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. File:Aldimine-(primary)-skeletal.svg, Primary aldimine, E-isomer File:Aldimine-(secondary)-skeletal.svg, Secondary aldimine, E-isomer File:Imine-(primary)-skeletal.svg, Primary ketimine File:Imine-(secondary)-skeletal.svg, Secondary ketimine File:Aziridine.svg, Aziridine and its derivatives are sometimes referred to as imines. N-Sulfinyl imines are a special class of imines having a sulfinyl group attached to the nitrogen atom.


Synthesis of imines

:


Carbonyl-amine condensation

Imines are typically prepared by the condensation of primary amines and aldehydes or ketones. Ketones undergo similar reactions, but less commonly than aldehydes. In terms of mechanism, such reactions proceed via the
nucleophilic addition In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electrophilic double or triple bond reacts with a nucleophile, such that the double or triple bond is broken. Nucleophilic additions ...
giving a hemiaminal -C(OH)(NHR)- intermediate, followed by an
elimination Elimination may refer to: Science and medicine * Elimination reaction, an organic reaction in which two functional groups split to form an organic product *Bodily waste elimination, discharging feces, urine, or foreign substances from the bo ...
of water to yield the imine (see alkylimino-de-oxo-bisubstitution for a detailed mechanism). The equilibrium in this reaction usually favors the
carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...
compound and amine, so that azeotropic distillation or use of a dehydrating agent, such as molecular sieves or
magnesium sulfate Magnesium sulfate or magnesium sulphate (in English-speaking countries other than the US) is a chemical compound, a salt with the formula , consisting of magnesium cations (20.19% by mass) and sulfate anions . It is a white crystalline solid, ...
, is required to favor of imine formation. In recent years, several reagents such as Tris(2,2,2-trifluoroethyl)borate (OCH2CF3)3 pyrrolidine or titanium ethoxide i(OEt)4have 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 Primary or primaries may refer to: Arts, entertainment, and media Music Groups and labels * Primary (band), from Australia * Primary (musician), hip hop musician and record producer from South Korea * Primary Music, Israeli record label Work ...
ketimines can be synthesized via a Grignard reaction with a nitrile. This method is known as Moureu-Mignonac ketimine synthesis. For example,
benzophenone imine Benzophenone imine is an organic compound with the formula of (C6H5)2C=NH. A pale yellow liquid, benzophenone imine is used as a reagent in organic synthesis. Synthesis Benzophenone imine can be prepared by the thermal decomposition of benzophen ...
can also be synthesized by addition of
phenylmagnesium bromide Phenylmagnesium bromide, with the simplified formula , is a magnesium-containing organometallic compound. It is commercially available as a solution in diethyl ether or tetrahydrofuran (THF). Phenylmagnesium bromide is a Grignard reagent. It i ...
to
benzonitrile Benzonitrile is the chemical compound with the formula , abbreviated PhCN. This aromatic organic compound is a colorless liquid with a sweet bitter almond odour. It is mainly used as a precursor to the resin benzoguanamine. Production It is ...
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). * Condensation of carbon acids with
nitroso In organic chemistry, nitroso refers to a functional group in which the nitric oxide () group is attached to an organic moiety. As such, various nitroso groups can be categorized as ''C''-nitroso compounds (e.g., nitrosoalkanes; ), ''S''-nitroso ...
compounds. * The rearrangement of trityl N-haloamines in the Stieglitz rearrangement. * By reaction of
alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
s 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 In organic chemistry an enol ether is an alkene with an alkoxy substituent. The general structure is R2C=CR-OR where R = H, alkyl or aryl. A common subfamily of enol ethers are vinyl ethers, with the formula ROCH=CH2. Important enol ethers includ ...
to a
quinoline Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only ...
in the Povarov reaction. *Imines react, thermally, with ketenes in +2cycloadditions 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
allyl In organic chemistry, an allyl group is a substituent with the structural formula , where R is the rest of the molecule. It consists of a methylene bridge () attached to a vinyl group (). The name is derived from the scientific name for garlic, ...
ic
amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
s in the
Aza-Baylis–Hillman reaction The aza-Baylis–Hillman reaction or aza-BH reaction in organic chemistry is a variation of the Baylis–Hillman reaction and describes the reaction of an electron deficient alkene, usually an α,β-unsaturated carbonyl compound, with an imine in ...
.


Acid-base reactions

Somewhat like the parent amines, imines are mildly basic and reversibly protonate to give iminium salts: :R2C=NR' + H+ 2C=NHR'sup>+ Alternatively, primary imines are sufficiently acidic to allow N-alkylation, as illustrated with
benzophenone imine Benzophenone imine is an organic compound with the formula of (C6H5)2C=NH. A pale yellow liquid, benzophenone imine is used as a reagent in organic synthesis. Synthesis Benzophenone imine can be prepared by the thermal decomposition of benzophen ...
: :(C6H5)2C=NH + CH3Li → (C6H5)2C=NLi + CH4 :(C6H5)2C=NLi + CH3I → (C6H5)2C=NCH3 + LiI


Lewis acid-base reactions

Imines are common
ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ele ...
s in
coordination chemistry A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ''ligands'' or complexing ...
. Particularly popular examples are found with Schiff base ligands derived from
salicylaldehyde Salicylic aldehyde (2-hydroxybenzaldehyde) is the organic compound with the formula (C7 H6 O2) C6H4CHO-2-OH. Along with 3-hydroxybenzaldehyde and 4-hydroxybenzaldehyde, it is one of the three isomers of hydroxybenzaldehyde. This colorless oi ...
, the salen ligands. Metal-catalyzed reactions of imines proceed through such complexes. In classical
coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
es, 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 allow for the synthesis of secondary amines: :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 In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
via
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate org ...
for example in a synthesis of ''m''-tolylbenzylamine: : Other reducing agents are
lithium aluminium hydride Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
and sodium borohydride. The
asymmetric Asymmetric may refer to: *Asymmetry in geometry, chemistry, and physics Computing * Asymmetric cryptography, in public-key cryptography *Asymmetric digital subscriber line, Internet connectivity * Asymmetric multiprocessing, in computer architect ...
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 In chemistry, transfer hydrogenation is a chemical reaction involving the addition of hydrogen to a compound from a source other than molecular . It is applied in laboratory and industrial organic synthesis to saturate organic compounds and r ...
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 Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
, which gives the hexahydro-1,3,5-triazine. Imine polymers (polyimines) can be synthesised from multivalent
aldehydes In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
and
amines In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
. 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-
diamine A diamine is an amine with exactly two amino groups. Diamines are used as monomers to prepare polyamides, polyimides, and polyureas. The term ''diamine'' refers mostly to primary diamines, as those are the most reactive. In terms of quantiti ...
s. Imine are oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an
oxaziridine An oxaziridine is an organic molecule that features a three-membered heterocycle containing oxygen, nitrogen, and carbon. In their largest application, oxaziridines are intermediates in the industrial production of hydrazine. Oxaziridine de ...
s. 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 In organophosphorus chemistry, the Pudovik reaction is a method for preparing α-aminomethylphosphonates. Under basic conditions, the phosphorus–hydrogen bond of a dialkylphosphite, (RO)2P(O)H, adds across the carbon–nitrogen double b ...
and
Kabachnik–Fields reaction In organophosphorus chemistry, the Kabachnik–Fields reaction is a three-component organic reaction forming aminophosphonate, α-aminomethylphosphonates from an amine, a carbonyl compound, and a phosphite ester, dialkyl phosphonate, (RO)2P(O)H (tha ...


Biological role

Imines are common in nature. The
pyridoxal phosphate Pyridoxal phosphate (PLP, pyridoxal 5'- phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-depende ...
-dependent enzymes (PLP enzymes) catalyze myriad reactions involving aldimines (or Schiff bases).


See also

* Enamine *
Schiff base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...
* Carboximidate * Oxime * Oxazolidine * Other functional groups with a CN double bond: oximes, hydrazones * Other functional groups with a CN triple bond: nitriles, isonitriles


References

{{Authority control Functional groups