Schiff base
{{Short description|1=Organic compound containing the group >C=N–}}
{{Distinguish|Schiff test}}
Image:Imine general structure B.svg. Schiff bases are imines in which {{chem2|R^{3} }} is an alkyl or aryl group (not a hydrogen). {{chem2|R^{1} }} and {{chem2|R^{2} }} may be hydrogens]]
File:Aldimine-(secondary)-skeletal.svg
In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure {{chem2|R^{1}R^{2}C\dNR^{3} }} ({{chem2|R^{3} }} = alkyl or aryl, but not hydrogen).{{GoldBookRef |title = Schiff base|file = S05498}}{{March6th|page=1281}} They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimines depending on their structure. Anil refers to a common subset of Schiff bases: imines derived from anilines.{{GoldBookRef|title = anil|file = A00357}} The term can be synonymous with azomethine which refers specifically to secondary aldimines (i.e. {{chem2|R\sCH\dNR'}} where R' ≠ H).{{GoldBookRef|title = azomethines|file = A00564}}
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'-oxydianiline reacts with o-vanillin:{{Cite journal| last = Jarrahpour| first = A. A.|author2=M. Zarei | title = Synthesis of 2-({[4-(4-
File:Schiff Base.png 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%)]]Schiff bases can also be synthesized via the Aza-Wittig reaction.
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.{{cite book|last1=Bajema|first1=Elizabeth A. |last2=Roberts|first2=Kaleigh F. |last3=Meade|first3=Thomas J. |editor1-last=Sigel|editor1-first=Astrid|editor2-last=Freisinger|editor2-first=Eva
|editor3-last=Sigel|editor3-first=Roland K. O. |editor4-last=Carver|editor4-first=Peggy L. |title=Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic
|series=Metal Ions in Life Sciences |volume=19 |date=2019 |publisher=de Gruyter GmbH|location=Berlin|isbn=978-3-11-052691-2|doi=10.1515/9783110527872-017|pmid=30855112|pages=267–301|chapter=Chapter 11. Cobalt-Schiff Base Complexes:Preclinical Research and Potential Therapeutic Uses|s2cid=73727460 }}
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 pyridoxal phosphate (PLP) forms a Schiff base with a lysine residue and is transaldiminated to the substrate(s).{{Cite journal|last1 = Eliot|first1 = A. C.|last2 = Kirsch|first2 = J. F.|doi = 10.1146/annurev.biochem.73.011303.074021|title = PYRIDOXALPHOSPHATEENZYMES: Mechanistic, Structural, and Evolutionary Considerations|journal = Annual Review of Biochemistry|volume = 73|pages = 383–415|year = 2004|pmid = 15189147|s2cid = 36010634}} 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
The term Schiff base is normally applied to these compounds when they are being used as ligands to form coordination complexes with metal ions.{{cite journal |first1=Malgorzata T. |last1=Kaczmarek |first2=Michal |last2=Zabiszak |first3=Martyna |last3=Nowak |first4=Renata |last4=Jastrzab |title=Lanthanides: Schiff base complexes, applications in cancer diagnosis, therapy, and antibacterial activity |journal=Coordination Chemistry Reviews |year=2018 |volume=370 |page=42–54 |doi=10.1016/j.ccr.2018.05.012}} One example is Jacobsen's catalyst. The imine nitrogen is basic and exhibits pi-acceptor properties. Several, especially the diiminopyridines are noninnocent ligands. Many Schiff base ligands are derived from alkyl diamines and aromatic aldehydes.{{cite book|doi=10.1016/B0-08-043748-6/01070-7|chapter=Acyclic and Macrocyclic Schiff Base Ligands|title=Comprehensive Coordination Chemistry II|pages=411–446|year=2003|last1=Hernández-Molina|first1=R.|last2=Mederos|first2=A.|isbn=9780080437484}}
{{Gallery|title=Schiff base ligands|width=200px|height=150px|align=center|File:Cu(Salox)2.png|Copper(II) complex of the Schiff base ligand salicylaldoxime.|File:Salen structure.svg|Salen is a common tetradentate ligand that becomes deprotonated upon complexation.|File:Jacobsen's catalyst (S,S).png|Jacobsen's catalyst is derived from a chiral salen ligand.|File:DIPMLn.svg|Generic diiminopyridine complex}}
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.{{cite journal|title = Homogeneous catalysis in the decomposition of diazo compounds by copper chelates: Asymmetric carbenoid reactions|journal = Tetrahedron|volume = 24|issue = 9|year = 1968|pages = 3655–3669|doi = 10.1016/S0040-4020(01)91998-2|last1 = Nozaki|first1 = H.|last2 = Takaya|first2 = H.|last3 = Moriuti|first3 = S.|last4 = Noyori|first4 = R.}} Schiff bases have also been incorporated into metal–organic frameworks (MOF).{{cite journal|title = A Crystalline Imine-Linked 3-D Porous Covalent Organic Framework|journal = J. Am. Chem. Soc.|volume = 131|issue = 13|year = 2009|pages = 4570–4571|doi = 10.1021/ja8096256|pmid=19281246|last1 = Uribe-Romo|first1 = Fernando J.|last2 = Hunt|first2 = Joseph R.|last3 = Furukawa|first3 = Hiroyasu|last4 = KlöCk|first4 = Cornelius|last5 = o'Keeffe|first5 = Michael|last6 = Yaghi|first6 = Omar M.}}
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.
Historic references
- {{cite journal|last1=Schiff|first1=Hugo|title=Mittheilungen aus dem Universitäts-laboratorium in Pisa: 2. Eine neue Reihe organischer Basen|journal=Annalen der Chemie und Pharmacie|date=1864|volume=131|pages=118–119|url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457965;view=1up;seq=130|trans-title=Communications from the university laboratory in Pisa: 2. A new series of organic bases|language=de|doi=10.1002/jlac.18641310113}}
- {{cite journal|last1=Schiff|first1=Ugo|title=Sopra una nova serie di basi organiche|journal=Giornale di Scienze Naturali ed Economiche|date=1866|volume=2|pages=201–257|url=http://babel.hathitrust.org/cgi/pt?id=hvd.32044106232283;view=1up;seq=207|trans-title=On a new series of organic bases|language=it}}
- {{cite journal|last1=Schiff|first1=Hugo|title=Eine neue Reihe organischer Diamine|journal=Annalen der Chemie und Pharmacie, Supplementband|date=1866|volume=3|pages=343–370|url=https://babel.hathitrust.org/cgi/pt?id=uc1.b3483657;view=1up;seq=353|trans-title=A new series of organic diamines|language=de}}
- {{cite journal|last1=Schiff|first1=Hugo|title=Eine neue Reihe organischer Diamine. Zweite Abtheilung.|journal=Annalen der Chemie und Pharmacie|date=1866|volume=140|pages=92–137|url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457971;view=1up;seq=488|trans-title=A new series of organic diamines. Second part.|language=de|doi=10.1002/jlac.18661400106}}