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 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.[4] 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.[5]
Nomenclature and classificationedit
The term "imine" was coined in 1883 by the German chemist Albert Ladenburg.[6]
Usually imines refer to compounds with the general formula R2C=NR, as discussed below.[7] In the older literature, imine refers to the aza-analogue of an epoxide. Thus, ethylenimine is the three-membered ring species aziridine C2H4NH.[8] 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.[9] 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.[10] 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.[11]
Rarer than primary amines is the use of ammonia to give a primary imine.[17] In the case of hexafluoroacetone, the hemiaminal intermediate can be isolated.[18]
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:[28]
(C6H5)2C=NH + CH3Li → (C6H5)2C=NLi + CH4
(C6H5)2C=NLi + CH3I → (C6H5)2C=NCH3 + LiI
Lewis acid-base reactionsedit
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 additionsedit
Very analogous to ketones and aldehydes, primary imines are susceptible to attack by carbanion equivalents. The method allow for the synthesis of secondary amines:[29][30]
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.
Imine polymers (polyimines) can be synthesised from multivalent aldehydes and amines.[36] 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.[37][38]
Imines are common in nature.[40][41] The pyridoxal phosphate-dependent enzymes (PLP enzymes) catalyze myriad reactions involving aldimines (or Schiff bases).[42] Cyclic imines are also substrates for many imine reductase enzymes.[43]
^March, Jerry (1985). Advanced Organic Chemistry Reactions, Mechanisms and Structure (3rd ed.). New York: Wiley, inc. ISBN 0-471-85472-7. OCLC 642506595.
^Saul Patai, ed. (1970). Carbon–Nitrogen Double Bonds. PATai's Chemistry of Functional Groups. John Wiley & Sons. doi:10.1002/9780470771204. ISBN 9780471669425. OCLC 639112179.
^C. Sandorfy (1970). "General and theoretical aspects". In Saul Patai (ed.). Carbon–Nitrogen Double Bonds. PATai's Chemistry of Functional Groups. John Wiley & Sons. pp. 1–60. doi:10.1002/9780470771204.ch1. ISBN 9780470771204.
^Bjørgo, Johannes; Boyd, Derek R.; Watson, Christopher G.; Jennings, W. Brian; Jerina, Donald M. (1974). "E–Z-isomerism in Aldimines". J. Chem. Soc., Perkin Trans. 2 (9): 1081–1084. doi:10.1039/P29740001081.
^Ladenburg, A. (1883). "Ueber die Imine" [About imines]. Berichte der Deutschen Chemischen Gesellschaft (in German). 16: 1149–1152. doi:10.1002/cber.188301601259. From p. 1150: Denn offenbar gehört auch das Piperidin in die Klasse der von mir gesuchten Verbindungen, für welche der Name Imine durch die bestehende Nomenklatur angezeigt ist. [For obviously piperidine also belongs in the class of compounds that are sought by me, for which the name "imines" is indicated by the prevailing nomenclature.]
^"Amines and Imines". Nomenclature of Organic Compounds. Advances in Chemistry. Vol. 126. American Chemical Society. 1974. pp. 180–188. doi:10.1021/ba-1974-0126.ch023. ISBN 9780841201910. OCLC 922539.
^Bigelow, Lucius A.; Eatough, Harry (1928). "Benzalaniline". Organic Syntheses. 8: 22. doi:10.15227/orgsyn.008.0022.
^Reeves, Jonathan T.; Visco, Michael D.; Marsini, Maurice A.; Grinberg, Nelu; Busacca, Carl A.; Mattson, Anita E.; Senanayake, Chris H. (2015-05-15). "A General Method for Imine Formation Using B(OCH2CF3)3". Organic Letters. 17 (10): 2442–2445. doi:10.1021/acs.orglett.5b00949. ISSN 1523-7060. PMID 25906082.
^Morales, Sara; Guijarro, Fernando G.; García Ruano, José Luis; Cid, M. Belén (2014-01-22). "A General Aminocatalytic Method for the Synthesis of Aldimines". Journal of the American Chemical Society. 136 (3): 1082–1089. doi:10.1021/ja4111418. ISSN 0002-7863. PMID 24359453.
^Collados, Juan F.; Toledano, Estefanía; Guijarro, David; Yus, Miguel (2012-07-06). "Microwave-Assisted Solvent-Free Synthesis of Enantiomerically Pure N-(tert-Butylsulfinyl)imines". The Journal of Organic Chemistry. 77 (13): 5744–5750. doi:10.1021/jo300919x. ISSN 0022-3263. PMID 22694241.
^Verardo, G.; Giumanini, A. G.; Strazzolini, P.; Poiana, M. (1988). "Ketimines From Ketones and Ammonia". Synthetic Communications. 18 (13): 1501–1511. doi:10.1080/00397918808081307.
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^"Moureau-Mignonac Ketimine Synthesis". Comprehensive Organic Name Reactions and Reagents. Hoboken, NJ, USA: John Wiley & Sons, Inc. 2010-09-15. pp. 1988–1990. doi:10.1002/9780470638859.conrr446. ISBN 9780470638859.
^Koos, Miroslav; Mosher, Harry S. (1993). "α-Amino-α-trifluoromethyl-phenylacetonitrile: A potential reagent for NMR determination of enantiomeric purity of acids". Tetrahedron. 49 (8): 1541–1546. doi:10.1016/S0040-4020(01)80341-0.
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^Mandler, Michael; Truong, Phong; Zavalij, Peter; Doyle, Michael (Jan 14, 2014). "Catalytic Conversion of Diazocarbonyl Compounds to Imines: Applications to the Synthesis of Tetrahydropyrimidines and β-Lactams". Organic Letters. 16 (3): 740–743. doi:10.1021/ol403427s. PMID 24423056.
^Vincent Rodeschini, Nigel S. Simpkins, and Fengzhi Zhang (2007). "Chiral Lithium Amide Base Desymmetrization of a Ring Fused Imide: Formation of (3aS,7aS)-2[2-(3,4-Dimethoxyphenyl)-ethyl]-1,3-dioxo-octahydro-isoindole-3a-Carboxylic Acid Methyl Ester". Organic Syntheses. 84: 306. doi:10.15227/orgsyn.084.0306.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^C. F. H. Allen and James VanAllan (1955). "m-Tolylbenzylamine". Organic Syntheses: 827; Collected Volumes, vol. 3.
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^Schoustra, Sybren K.; Dijksman, Joshua A.; Zuilhof, Han; Smulders, Maarten M. J. (2021). "Molecular control over vitrimer-like mechanics – tuneable dynamic motifs based on the Hammett equation in polyimine materials". Chemical Science. 12 (1): 293–302. doi:10.1039/d0sc05458e. ISSN 2041-6520. PMC8178953. PMID 34163597.
^Zhu, Jiaqi (2020). "A self-healing transparent polydimethylsiloxane elastomer based on imine bonds". European Polymer Journal. 123: 109382. Bibcode:2020EurPJ.12309382W. doi:10.1016/j.eurpolymj.2019.109382. S2CID 214199868.
^Alexakis, Alex; Aujard, Isabelle; Kanger, Tonis; Mangeney, Pierre (1999). "(R,R)- and (S,S)-N,N'-Dimethyl-1,2-Diphenylethylene-1,2-Diamine". Organic Syntheses. 76: 23. doi:10.15227/orgsyn.076.0023.
^"Researchers look to nature to unearth the secrets of cyclic imine cleavage". EurekAlert!. Retrieved 2021-07-22.
^Borchert, Andrew J.; Ernst, Dustin C.; Downs, Diana M. (2019). "Reactive Enamines and Imines in vivo: Lessons from the RidA Paradigm". Trends in Biochemical Sciences. 44 (10): 849–860. doi:10.1016/j.tibs.2019.04.011. ISSN 0968-0004. PMC6760865. PMID 31103411.
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^Mangas-Sanchez, Juan; France, Scott P; Montgomery, Sarah L; Aleku, Godwin A; Man, Henry; Sharma, Mahima; Ramsden, Jeremy I; Grogan, Gideon; Turner, Nicholas J (2017). "Imine reductases (IREDs)". Current Opinion in Chemical Biology. 37: 19–25. doi:10.1016/j.cbpa.2016.11.022. PMID 28038349.