Schiff base

General structure of an imine. Schiff bases are imines in which R³ is an alkyl or aryl group (not a hydrogen). R¹ and R² may be hydrogens

General structure of an azomethine compound

A Schiff base (named after Hugo Schiff) is a compound with the general structure R₁R₂C=NR' (R' ≠ H).^[1]^[2]^[3]^[4]^[5] They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimines depending on their structure. The term is often synonymous with azomethine which refers specifically to secondary aldimines (i.e. R-CH=NR' where R' ≠ H).^[6]

A number of special naming systems exist for these compounds. For instance a Schiff base derived from an aniline, where R³ is a phenyl or a substituted phenyl, can be called an anil,^[7] while bis-compounds are often referred to as salen-type compounds.

The term Schiff base is normally applied to these compounds when they are being used as ligands to form coordination complexes with metal ions. Such complexes occur naturally, for instance in corrin, but the majority of Schiff bases are artificial and are used to form many important catalysts, such as Jacobsen's catalyst.

Synthesis[]

Schiff bases can be synthesized from an aliphatic or aromatic amine and a carbonyl compound by nucleophilic addition forming a hemiaminal, followed by a dehydration to generate an imine. In a typical reaction, 4,4'-diaminodiphenyl ether reacts with o-vanillin:^[8]

A mixture of 4,4'-oxydianiline 1 (1.00 g, 5.00 mmol) and o-vanillin 2 (1.52 g, 10.0 mmol) in methanol (40.0 ml) is stirred at room temperature for one hour to give an orange precipitate and after filtration and washing with methanol to give the pure Schiff base 3 (2.27 g, 97%)

Biochemistry[]

Schiff bases have been investigated in relation to a wide range of contexts, including antimicrobial, antiviral and anticancer activity. They have also been considered for the inhibition of amyloid-β aggregation. ^[9]

Schiff bases are common enzymatic intermediates where an amine, such as the terminal group of a lysine residue, reversibly reacts with an aldehyde or ketone of a cofactor or substrate. The common enzyme cofactor PLP forms a Schiff base with a lysine residue and is transaldiminated to the substrate(s).^[10] Similarly, the cofactor retinal forms a Schiff base in rhodopsins, including human rhodopsin (via Lysine 296), which is key in the photoreception mechanism.

Coordination chemistry[]

Schiff bases are common ligands in coordination chemistry. The imine nitrogen is basic and exhibits pi-acceptor properties. The ligands are typically derived from alkyl diamines and aromatic aldehydes.^[11]

Schiff base ligands

Copper(II) complex of the Schiff base ligand salicylaldoxime.
Salen is a common tetradentate ligand that becomes deprotonated upon complexation.
Jacobsen's catalyst is derived from a chiral salen ligand.

Chiral Schiff bases were one of the first ligands used for asymmetric catalysis. In 1968 Ryōji Noyori developed a copper-Schiff base complex for the metal-carbenoid cyclopropanation of styrene.^[12] For this work he was later awarded a share of the 2001 Nobel Prize in Chemistry. Schiff bases have also been incorporated into MOFs.^[13]

Conjugated Schiff bases[]

Conjugated Schiff bases absorb strongly in the UV-visible region of the electromagnetic spectrum. This absorption is the basis of the anisidine value, which is a measure of oxidative spoilage for fats and oils.

Nanotechnology[]

Formation of metal clusters in halloysite nanotubes via a Schiff base reaction on example of ruthenium.^[14]

Schiff bases can be used to mass-produce nanoclusters of transition metals inside halloysite. This abundant mineral naturally has a structure of rolled nanosheets (nanotubes), which can support both the synthesis and the metal nanocluster products. These nanoclusters can be made of Ag, Ru, Rh, Pt or Co metals and can catalyze various chemical reactions.^[14]

References[]

^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Schiff base". doi:10.1351/goldbook.S05498
^ Schiff, Hugo (1864). "Mittheilungen aus dem Universitäts-laboratorium in Pisa: 2. Eine neue Reihe organischer Basen" [Communications from the university laboratory in Pisa: 2. A new series of organic bases]. Annalen der Chemie und Pharmacie (in German). 131: 118–119. doi:10.1002/jlac.18641310113.
^ Schiff, Ugo (1866). "Sopra una nova serie di basi organiche" [On a new series of organic bases]. Giornale di Scienze Naturali ed Economiche (in Italian). 2: 201–257.
^ Schiff, Hugo (1866). "Eine neue Reihe organischer Diamine" [A new series of organic diamines]. Annalen der Chemie und Pharmacie, Supplementband (in German). 3: 343–370.
^ Schiff, Hugo (1866). "Eine neue Reihe organischer Diamine. Zweite Abtheilung" [A new series of organic diamines. Second part.]. Annalen der Chemie und Pharmacie (in German). 140: 92–137. doi:10.1002/jlac.18661400106.
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "azomethines". doi:10.1351/goldbook.A00564
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "anils". doi:10.1351/goldbook.A00357
^ Jarrahpour, A. A.; M. Zarei (February 24, 2004). "Synthesis of 2-({[4-(4-{[(E)-1-(2-hydroxy-3-methoxyphenyl)methylidene amino}phenoxy)phenyl imino}methyl)- 6 -methoxy phenol". Molbank. M352. ISSN 1422-8599. Retrieved February 22, 2010.
^ Bajema, Elizabeth A.; Roberts, Kaleigh F.; Meade, Thomas J. (2019). "Chapter 11. Cobalt-Schiff Base Complexes:Preclinical Research and Potential Therapeutic Uses". In Sigel, Astrid; Freisinger, Eva; Sigel, Roland K. O.; Carver, Peggy L. (Guest editor) (eds.). Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic. Metal Ions in Life Sciences. 19. Berlin: de Gruyter GmbH. pp. 267–301. doi:10.1515/9783110527872-017. ISBN 978-3-11-052691-2. PMID 30855112.
^ Eliot, A. C.; Kirsch, J. F. (2004). "PYRIDOXALPHOSPHATEENZYMES: Mechanistic, Structural, and Evolutionary Considerations". Annual Review of Biochemistry. 73: 383–415. doi:10.1146/annurev.biochem.73.011303.074021. PMID 15189147. S2CID 36010634.
^ Hernández-Molina, R.; Mederos, A. (2003). "Acyclic and Macrocyclic Schiff Base Ligands". Comprehensive Coordination Chemistry II. pp. 411–446. doi:10.1016/B0-08-043748-6/01070-7. ISBN 9780080437484.
^ Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. (1968). "Homogeneous catalysis in the decomposition of diazo compounds by copper chelates: Asymmetric carbenoid reactions". Tetrahedron. 24 (9): 3655–3669. doi:10.1016/S0040-4020(01)91998-2.
^ Uribe-Romo, Fernando J.; Hunt, Joseph R.; Furukawa, Hiroyasu; KlöCk, Cornelius; o'Keeffe, Michael; Yaghi, Omar M. (2009). "A Crystalline Imine-Linked 3-D Porous Covalent Organic Framework". J. Am. Chem. Soc. 131 (13): 4570–4571. doi:10.1021/ja8096256. PMID 19281246.
^ ^a ^b Vinokurov, Vladimir A.; Stavitskaya, Anna V.; Chudakov, Yaroslav A.; Ivanov, Evgenii V.; Shrestha, Lok Kumar; Ariga, Katsuhiko; Darrat, Yusuf A.; Lvov, Yuri M. (2017). "Formation of metal clusters in halloysite clay nanotubes". Science and Technology of Advanced Materials. 18 (1): 147–151. Bibcode:2017STAdM..18..147V. doi:10.1080/14686996.2016.1278352. PMC 5402758. PMID 28458738.