Open access peer-reviewed chapter
Abstract
Schiff bases, which were first obtained by the German chemist H. Schiff in 1864, are used in the paint industry, polymer technology, pharmaceutical industry, medicine, agriculture, preparation of rocket fuel, and explanation of biological events, and in many other areas due to the groups in their structures. This chapter will be a guide that contains a summary of general information that should be known about these compounds, which have a wide range of use in our daily life. In this chapter, the following topics are planned to be explained. (1) Schiff bases, physical and chemical properties, (2) the formation mechanism of Schiff bases, (3) Schiff base reactions, (4) metal complexes of Schiff base, (5) classification of Schiff bases, (6) biological activity of Schiff bases, and (7) usage of Schiff bases.
Keywords
- Schiff bases
- azomethine
- biological activity
- metal complexes
- formation mechanism
1. Introduction
Compounds that are formed as a result of the nucleophilic addition reaction of aldehydes and ketones with primary amines under suitable conditions and which have carbon-nitrogen double bonds (▬CH〓N▬) in their structure are called Schiff bases. Schiff bases, which were first obtained by the German chemist H. Schiff in 1864 [1], were started to be used as ligands by Pfeiffer in the 1930s [2, 3] (Figure 1).
Figure 1.
General representation of Schiff bases.
Aldehydes react very easily with primary amines to form Schiff bases, but this process is not so easy for ketones. In order to obtain Schiff bases from ketones, it is necessary to pay attention to factors, such as the choice of catalyst, the appropriate pH range, the selection of a solvent that can form an azeotrope mixture with the water to be formed in the reaction, and the appropriate reaction temperature. The carbon-nitrogen double bond in Schiff bases formed as a result of the reaction of primary amines with aldehydes is called azomethine or aldimine, while the bond formed as a result of reaction with ketone is called imine or ketimine.
Schiff bases are selective toward metal ions and form complexes by transferring electrons from the active ends they contain to the metal. Schiff bases are known as a good nitrogen donor ligand (▬CH〓N▬). During the formation of the coordination compound, one or more electron pairs are donated to the metal ion by these ligands. Schiff bases can form highly stable 4-, 5-, and 6-ring complexes if they donate more than one electron pair. For this, a second functional group with a displaceable hydrogen atom must be found as close as possible to the azomethine group. This group is preferably the hydroxyl group [4].
2. Physical properties of Schiff bases
Schiff bases are usually colored and transparent solids. They are used in the determination of metal amounts and in the identification of carbonyl compounds due to their precise melting points.
The carbon-nitrogen double bond in Schiff bases rotates more easily than the carbon-carbon double bond, which allows stereoisomers to transform into each other. The reason for this: polarization occurs in the azomethine bond due to the fact that nitrogen is more electronegative than carbon (Figure 2).
Figure 2.
Polarization of azomethine bond.
The stereoisomers of Schiff bases cannot be isolated with a few exceptions due to the very small energy difference between them. If only an electronegative group is attached to the nitrogen atom, stereoisomers become isolated, since this group reduces the ease of rotation around the azomethine bond. Since the electronegative group attached to the nitrogen atom in the azomethine group will push the negative charges of the nitrogen atom toward the carbon, this will cause a decrease in polarization and an increase in the character of the covalent double bond.
All compounds containing an azomethine group show basic properties due to the unshared electron pairs on the nitrogen atom and the electron donating feature of the double bond. Schiff bases show weaker basic properties compared to their corresponding amines. The reason for this is that while the nitrogen atom in amines undergoes sp3 hybridization, this hybridization turns into sp2 hybridization when the imine structure is formed. Since the s character will increase in hybridization, the basicity will decrease greatly.
The C〓N system is a weak chromophore that shows absorption in the ultraviolet field. Conjugation with phenyl groups shifts absorption to the visible region. When there is a deactivating substituent in the aromatic ring, such as a halogen, the wavelength of absorption decreases. Generally, aryl alkyl ketimines are absorbed at values between dialkyl and diaryl ketimines [5]. The IR stretch bands of the C〓N system are generally observed at 1610–1635 cm−1 and that of C〓N+ at 1665–1690 cm−1 [6].
3. Chemical properties of Schiff bases
Schiff bases have many properties that vary according to the substituents attached to the azomethine group. The stability of the azomethine compound increases when there is an electronegative group attached to the nitrogen atom. The best example of this is that oximes carrying hydroxyl groups on the nitrogen atom along with phenylhydrazone and semicarbazones carrying ▬NH groups are much more stable to hydrolysis than Schiff bases carrying alkyl or aryl substituents on the nitrogen atom. Although Schiff bases are stable against alkalies, they are separated into amine and carbonyl compounds by hydrolysis in acidic environment.
The Schiff base formation reaction is reversible. As a result of the reaction, one mole of water is formed and the water in the environment shifts the direction of the reaction to the left. Therefore, the reaction is usually carried out in solvents where water can be removed from the environment by distillation, forming an azeotrope. If the reaction is carried out using amines containing an electronegative atom with unpaired electrons in the nitrogen atom, the reaction is completed and since hydrolysis will not occur, Schiff bases can be isolated with high efficiency (Figure 3).
Figure 3.
Schiff base formation reaction.
The structures of Schiff bases are determined by the tautomeric transformations that occur depending on the polarity of the solvent and the hydrogen bonds that occur in the molecule. The preferred conformation in terms of the stability of Schiff bases is the nonplanar structure seen in Figure 4. This conformation has also been confirmed by quantum mechanics calculations [7].
Figure 4.
Preferred conformation of Schiff bases.
In the studies, it has been reported that there are two types of tautomer forms, phenol-imine and ketone-amine, in Schiff bases obtained by using aldehydes containing ortho hydroxy group (Figure 5). The presence of these two tautomeric structures was determined by spectroscopic methods such as 13CNMR, 1H-NMR, UV-Vis, and X-ray crystallography [8].
Figure 5.
Tautomeric structure of Schiff bases.
In studies with Schiff bases prepared from 2-hydroxy-1-naphthaldehyde and some aromatic and aliphatic amines (ammonia, methylamine, and phenylamine), it has been observed that the keto form is dominant in polar solvents, such as chloroform, and the enol form is dominant in nonpolar solvents [9, 10].
4. Formation mechanism of Schiff bases
The most widely used method discovered by Schiff for the preparation of Schiff bases is the reaction of aliphatic or aromatic aldehydes or ketones with aliphatic or aromatic primary amines. The synthesis of Schiff bases obtained from the reaction of carbonyl compounds with primary amines takes place in two main steps. In the first step, a carbinolamine intermediate is formed from the condensation of the carbonyl group with the primary amine, and in the second step, a Schiff base is formed from the dehydration of the intermediate seen in Figure 6 [12, 13, 14].
Figure 6.
Mechanism of condensation of carbonyl compounds with amines [
The formation of Schiff base is a pH-dependent reaction. Since the amine will form salt at low pH, the free amine concentration decreases and the fast addition step slows down and becomes the step that determines the rate of the reaction mechanism (Figure 7). In the case of a decrease in acidity, the addition step is faster and the elimination step is slower (Figure 8). The optimal pH is the pH between these two extremes (pH 3−4). This pH is suitable for both starting the nucleophilic addition reaction and performing elimination reaction at a sufficient speed [7].
Figure 7.
Increase in electrophilic power and decrease in nucleophilic power in acidic medium.
Figure 8.
Decrease in electrophilic power and increase in nucleophilic power in basic medium.
The effect of substitution is great on the stability of Schiff bases. Since small-molecular-weight aliphatic imines without substituents on the nitrogen atom are easily polymerized, detailed information about these imines is not available. Schiff bases containing aryl substituents can be synthesized more stable and easily due to the electron feeding of the imine bond through ring conjugation, while those containing alkyl substituents are relatively unstable, synthesized in a long time, and polymerization is observed.
In the formation of imine; aldehydes are more reactive than ketones because they are less sterically hindered. In addition, in ketones, groups attached to the carbonyl carbon donate electrons, reducing the electrophilic character of the carbonyl carbon, thus reducing the reaction tendency and causing the reaction to take place more slowly. Therefore, although aldehydes and primary amines can easily form Schiff bases, it is quite difficult to obtain Schiff bases from ketones. In order to obtain Schiff base from ketones, many factors, such as choosing a solvent that can form an azeotrope mixture with the water released during the reaction, choosing a catalyst, choosing the appropriate pH range and the appropriate reaction temperature, must be taken into account. Particularly in order to obtain Schiff base from aromatic ketones, high temperature, long reaction time, and catalyst are required [4, 15].
Aromatic aldehydes and ketones can form highly stable Schiff bases. Aromatic aldehydes react with amines at low temperature and in a suitable solvent environment. In the reaction of aromatic aldehydes with aromatic amines, it has been indicated that the reaction rate increases in the presence of an electron-withdrawing substituent in the para position of the aldehyde and decreases in the presence of para position of the amine. While the water formed in the reaction must be removed during the production of Schiff base from aromatic ketones, there is no need to remove water in the synthesis of Schiff base from aldehydes and dialkyl ketones. While the water formed in the reaction must be removed during the generation of Schiff base from aromatic ketones, there is no need to remove water in the synthesis of Schiff base from aldehydes and dialkyl ketones [16].
5. Synthesis methods of Schiff bases
5.1 Reaction of aldehydes and ketones with primary amines
The reaction of primary amines with carbonyl compounds is usually carried out by reflux. Since the reaction is reversible, the water formed in the reaction medium must be removed to prevent hydrolysis. Dean-Stark apparatus is generally used to remove water. In addition, the reaction was carried out successfully by using dehydration agents such as sodium sulfate and molecular sieve [17]. Moreover, methods using solvents, such as tetramethyl orthosilicate or trimethyl orthoformate, which remove water in the reaction medium, have also been reported in the literature [18, 19].
The reaction can be accelerated by acid catalysis. In such cases, mineral acids, such as H2SO4 or HCl, organic acids, such as p-toluene sulfonic acid, pyridinium p-toluenesulfonate, acidic resin, montmorillonite, or Lewis acids (ZnCl2, TiCl4, SnCl4, BF3Et2O, Mg(ClO4)2, MgSO4), can be used [15, 20, 21, 22, 23, 24, 25].
The reaction of aliphatic ketones with amines to form a Schiff base occurs more slowly than with aldehydes. When the reaction rates of the same primary amine and aldehydes and ketones are compared, it was found that the rate order was; the rate order is aromatic aldehyde>aliphatic aldehyde>aliphatic ketone>aromatic ketone [26]. Recently, new solvent-free techniques have been developed for imine formation, including clay, microwave irradiation, water suspension media, liquid crystal, molecular sieve, and infrared and ultrasonic irradiation [27, 28, 29, 30, 31, 32, 33, 34].
5.2 Reaction of organometallic compounds with nitriles
Grignard reagents can react with nitriles to form ketimines. Anhydrous hydrogen chloride or anhydrous ammonia is added to the reaction medium to prevent the hydrolysis of the intermediate products into ketones. With this method, intermediate products can be isolated with an efficiency of 50−90% (Figure 9) [26].
Figure 9.
Addition of organometallic reagents to nitriles.
5.3 Reaction of phenols and phenol ethers with nitriles
The alkyl or aryl nitriles react with phenol and phenol ethers with high efficiency under acid catalysis to form ketimines [35]. The reaction is carried out by saturating a solution of nitrile and phenol dissolved in ether with HCl gas. ZnCl2 should be used in reactions with lower reactivity phenols (Figure 10).
Figure 10.
Reaction of phenols with nitriles.
5.4 Aerobic oxidative synthesis method
Since aldehydes and ketones can be obtained from their corresponding alcohols by oxidative methods, it is also possible to prepare imines from alcohols and amines using oxidative processes (Figures 11 and 12) [36, 37, 38, 39, 40, 41, 42, 43].
Figure 11.
Oxidative synthesis of imines from alcohols and amines.
Figure 12.
Oxidative synthesis of imines from amines.
Following this general approach, Huang and Largeron developed new catalytic processes that convert primary and secondary amines to imines by aerobic oxidation under mild conditions [38, 39, 40, 41, 42, 43, 44].
5.5 Reaction of metal amides
Calcium or alkali metal salts of primary amines react with aromatic ketones to form Schiff bases [26].
6. Reactions of Schiff bases
6.1 Polymerization reaction
Many studies have been carried out on poly (Schiff bases) over time due to their thermal, conductive [45, 46, 47], fiber forming [48], liquid crystal [49, 50], and nonlinear optical properties [51, 52]. One of them is poly (Schiff base) formed by the reaction of diamines and dialdehydes by Catanescu et al. (Figure 13) [53].
Figure 13.
Polymer synthesis.
6.2 Reaction with Zn and haloesters
β-Lactams are formed as a result of the reaction of Schiff bases with Zn and haloesters at room temperature [54].
6.3 Reaction with HCN
Nitrile derivatives are formed from the reaction of Schiff bases with HCN, and α-amino acids are formed by their hydrolysis [54].
6.4 Reduction reactions
Schiff bases are reduced with LiAlH4, NaBH4, and Na-EtOH reagents to form secondary amines [54].
6.5 Hydrolysis
Since the reaction steps of Schiff bases synthesized with carbonyl compounds and amines are reversible, starting materials are obtained by hydrolysis of Schiff bases. In the first step of hydrolysis, the intermediate product, carbinolamine, is formed. In the second step, the carbinolamine is decomposed to form the reaction products aldehyde (or ketone) and amine. Hydrolysis reactions are mostly acid-catalyzed and the rate of the reaction depends on the acidity strength [5].
7. Schiff base metal complexes
Schiff bases are widely used as ligands in coordination chemistry. Ligands are called Lewis bases because they donate electron pairs to the central atom. Since the nitrogen atom in the imine bond contains unpaired electrons, Schiff bases are electron donors, basic in character, and can form complexes with almost all transition metals. This atom, also known as azomethine nitrogen, is the primary bonding point for the Schiff base. In addition, the azomethine system, where the nitrogen atom is bonded with a double bond, can be a coordination site for d-metal ions suitable for back bonding, by means of its π-orbitals. Thus, the azomethine group with the nitrogen atom has both σ-donor and π-acceptor functions. This provides high stability for metal complexes formed by Schiff bases. Schiff bases can form stable compounds with metal ions if they have a structure that can form a quintet or hexavalent chelate ring [55].
Apart from the fact that the azomethine group is basic, there must be a functional group in the molecule close to the azomethine bond, from which the hydrogen atom can be easily removed, in order to form stable complexes as a ligand. Since Schiff base ligands, which have groups such as OH and SH, in the ortho position adjacent to the azomethine bond, form a six-membered ring with the metal, stable complexes are formed [56].
The properties of complex compounds vary depending on the ligand and metal ion used. The size, charge, and ionization potential of the metal ion used in the formation of the complex affect the stability of the complex. Since the substituents can change the basicity of the Schiff base imine nitrogen, the ligand property also changes depending on the substituents. Therefore, the stability of the metal complexes of Schiff bases is more or less affected by the substituents in their structure.
Three methods are generally used to synthesize metal complexes of Schiff bases. These methods are direct interaction of metal salt with Schiff base [54]; condensation of aldehyde, amine, and metal salt with the effect of template [57]; and condensation of aldehyde complexes with amines [58].
The first studies on Schiff base metal complexes were made by spectrophotometric techniques [59]. Later, potentiometric studies were started by Leussing et al. When these studies were examined, it was seen that Schiff bases formed complexes with metal ions in 1:1 and 1:2 ratios [60].
7.1 Classification of Schiff base complexes
Classification of Schiff bases metal complexes is done by considering the donor atoms of the compound. Depending on the type and number of donor atoms they contain, some of the metal complexes encountered are those with N▬O, O▬N▬O, O▬N▬S, N▬N▬O, O▬N▬N▬O, and N▬N▬N▬N donor atom systems.
7.1.1 N▬O Type Schiff base complexes
N▬O type Schiff base formed by salicylaldehyde and p-N, N′-dimethylaniline is bidentate and forms a 1:1 complex with Ag+ ion (Figure 14) [61].
Figure 14.
N▬O type Schiff base metal complex.
7.1.2 O▬N▬O type Schiff base complexes
[ML]X2 type colored complexes synthesized with (E)–N′-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzohydrazide ligand are examples of O▬N▬O type Schiff base complexes (Figure 15). This ligand forms a complex with metal ions by reacting at a ratio of 2:1. M = Mn(II), Co(II), Ni(II), Cu(II), Sr(II) Cd(II), X = Cl− [62].
Figure 15.
O▬N▬O type Schiff base metal complex.
7.1.3 O▬N▬S type Schiff base complexes
Schiff base, which consists of 2-hydroxy-1-naphthaldehyde and 2-aminoetantiol, can be given as an example of such complexes. These complexes are tridentate and they have dibasic properties. The structure of the UO26+(VI) complex of this Schiff base is shown in Figure 16 [63].
Figure 16.
O▬N▬S type Schiff base metal complex.
7.1.4 N▬N▬O type Schiff base complexes
Co(II), Ni(II), and Cu(II) complexes of 4-Chloromethyl-2-(2-hydroxynaphthylidenehydrazine) thiazole ligand can be given as examples of such complexes [64] (Figure 17).
Figure 17.
N▬N▬O type Schiff base metal complex.
7.1.5 O▬N▬N-O type Schiff base complexes
An example of this group is the oxovanadium(IV) complex synthesized with the N,N′-bis(salicylidine)ethylenediamine ligand [65]. N,N′-bis(salicylidine)ethylenediamine Schiff base, which is obtained with the condensation reaction of salicylaldehyde and ethylenediamine, is commonly known as salen and is an ONNO type tetradentate ligand (Figure 18) [66].
Figure 18.
O▬N▬N▬O type Schiff base metal complex.
8. Biological activity of Schiff bases
Schiff bases and metal complexes are vital compounds for biological systems because they have anticancer [67, 68], antibacterial [69, 70, 71, 72, 73, 74], antifungal [75, 76], and antiviral [77] properties.
The most important biological activity of Schiff bases is the role they play in amino acid biosynthesis, one of the basic processes of life. Schiff bases are important intermediates formed in the biosynthesis of α-amino acids (RCHNH2COOH) used in the synthesis of proteins in organisms. If there is not enough essential amino acid in the food, the organism converts an excess amino acid to the amino acid it needs by transamination reaction in some cases. In this process, the amino group of the excess amino acid is transferred to the keto acid
Figure 20.
Transamination reaction through Schiff bases from amino acid to keto acid and vice versa [
In addition, Schiff bases have been proven to be present in a variety of natural, semisynthetic, and synthetic compounds and are essential for their biological activity (Figure 21) [26].
Figure 21.
Examples of biologically active Schiff bases.
9. The importance and uses of Schiff bases
Today, with the development of spectral methods, the mechanisms of biochemical reactions can be explained. It has been determined that some reactions in living organisms proceed on Schiff bases, Schiff bases eliminate the toxic effects of aldehyde and amine components and bind free metal ions. The importance of Schiff bases increases day by day as they can be used in biological systems [79], chemical catalysis [80], medicine and pharmacy [81], chemical analysis, and new technologies [82, 83] due to their properties. If we briefly summarize the reasons why Schiff bases have such a wide working area [84]:
Alternatively, Schiff bases can be synthesized by the template effect. This procedure directly gives the designed complexes. Also, these complexes can give transmetalation reactions when reacted with a different metal salt. This method ensures that complexes that cannot be obtained by different methods are obtained with sufficient purity and high yield.
Since Schiff bases generally contain additional donor groups, such as N, O, S, and P, they can form stable complexes with almost all metals. In addition to these features, they play important roles in biological systems.
Schiff bases are easily synthesized using carbonyl compounds and primary amines and can be functionalized in a wide variety of ways using appropriate groups.
When treated with suitable reducing agents, they can form polyamine derivatives that are more flexible and less sensitive to hydrolysis. These reduced compounds contain NH groups that can be further functionalized by suitable synthetic procedures.
By bonding to a suitable support, such as silica, they result in modified catalysts and different designed surfaces.
By binding groups, such as crown ether, macrocyclic thioether, and polyaza derivatives, special ligands can be formed to form selective systems with the capacity to bind different metal ions.
Due to the interaction of metal chelates with the DNA helix, they can be used in the design of new models in diagnosis and therapy.
In addition, due to their photochromism feature, they can be used in different fields, such as controlling and measuring radiation intensity, image systems, and optical computers [85]. Since the metal complexes of these compounds are colored substances, they are used as pigment dyestuffs in the dye industry, especially in textile dyeing [86, 87]. Moreover, they are widely used in the perfume and pharmaceutical industries. These compounds also have properties, such as synthetic oxygen carrier and intermediate in enzymatic reactions. They are also used as spectrophotometric reagents in analytical chemistry, as they react selectively and specifically to some metal ions. They can be used in aircraft construction, television and computer screens, and digital clock displays by taking advantage of the liquid crystal feature that occurs in some metal complexes [88].
10. Application of Schiff bases in organic synthesis
We can classify the reactions in which Schiff bases are used as precursors in four groups as seen in Figure 22 [26].
Addition of organometallic reagent or hydride to C=N bond to form asymmetric C-C bond [89, 90].
Hetero Diels-Alder reaction to produce six-membered nitrogen-containing heterocyclic compounds [91, 92, 93].
Use of chiral salen metal complexes in the asymmetric synthesis [94, 95, 96].
Staudinger reaction with ketene to provide biologically important β-lactams [97, 98, 99].
Figure 22.
Applications of Schiff bases as a starting material in organic synthesis.
References
- 1.
Schiff H. Untersuchungen Uber salicin derivate. European Journal of Organic Chemistry. 1869; 150 :193-200 - 2.
Pfeiffer P, Breith E, Lubbe E, Tsumaki T. Thcylische Orthokondesierte Nebenvalenzringe. Annalen Der Chemie. 1932; 492 :81-127 - 3.
Pfeiffer P, Breith E, Lubbe E, Tsumaki T. Thcylische Orthokondezierte Nebenvalenzringe. Annalen Der Chemie. 1933; 503 :84-127 - 4.
Patai S. The Chemistry of the Carbon-Nitrogen Double Bond. Norwich: Wiley; 1970 - 5.
Layter RW. The chemistry of imines. Chemical Reviews. 1963; 63 :489-510 - 6.
Smith PAS. The Chemistry of Open-Chain Organic Nitrogen Compounds. New York: Benjamin; 1965 - 7.
Ekmekcioglu P. Synthesis and Characterization of New Six Dentate Schiff Bases with Cu(II), Ni(II) and Co(II) Complexes. Trabzon: Karadeniz Technical University; 2015 - 8.
Metzler DE, Christen P. Transaminases. New York: John Wiley; 1985 - 9.
Dudek GO, Dudek EP. Spestrocopic Studies of Keto-Enol Equilibria. VII. Nitrogen-15 Substitued Schiff Bases. Journal of the American Chemical Society. 1964; 86 (209):4283-4287 - 10.
Dudek GO, Dudek EP. Spectroscopic Studies of Keto-Enol Equilibria. IX. N15-Substituted Anilides. Journal of the American Chemical Society. 1966; 88 (11):2407-2412 - 11.
Borisova NE, Reshetova MD, Ustynyuk YA. Metal-free methods in the synthesis of macrocyclic Schiff bases. Chemical Reviews. 2007; 107 :46-79 - 12.
Schiff H. Eine neue Reihe organischer Diamine (in German). Justus Liebigs Annalen der Chemie. 1866; 140 :92-137 - 13.
Robertson GM. Imines and their N-substituted derivatives: NH, NR and N-haloimines. In: Katritzky AR, Meth-Cohn O, Rees CW, editors. Comprehensive Organic Functional Group Transformations. 1st ed. Amsterdam, The Netherlands: Elsevier; 1995. pp. 403-423 - 14.
Dobbs AP, Rossiter S. Imines and their N-substituted derivatives: NH, NR, and N-Haloimines. In: Alan RK, Taylor RJK, editors. Comprehensive Organic Functional Group Transformations II. Oxford, UK: Elsevier; 2005. pp. 419-450 - 15.
Billman JH, Tai KM. Reduction of Schiff Bases. II. Benzhydrylamines structurally related compounds. The Journal of Organic Chemistry. 1958; 23 (4):535-539 - 16.
Pratt EF, Kamet MJ. Reaction rates by distillation. IX. The condensation of anilines with benzaldehydes. The Journal of Organic Chemistry. 1961; 26 (10):4029-4031 - 17.
Westheimer FH, Taguchi K. Catalysis by molecular sieves in the preparation of ketimines and enamines. The Journal of Organic Chemistry. 1971; 36 :1570-1572 - 18.
Love BE, Ren J. Synthesis of sterically hindered imines. The Journal of Organic Chemistry. 1993; 58 :5556-5557 - 19.
Look GC, Murphy MM, Campbell DA, Gallop MA. Trimethylorthoformate: A mild and effective dehydrating reagent for solution and solid phase imine formation. Tetrahedron Letters. 1995; 36 :2937-2940 - 20.
White WA, Weingarten H. A versatile new enamine synthesis. The Journal of Organic Chemistry. 1967; 32 :213-214 - 21.
Liu G, Cogan DA, Owens TD, Tang TP, Ellman JA. Synthesis of enantiomerically Pure N-tert-butanesulfinyl imines (tert-butanesulfinimines) by the direct condensation of tert-butanesulfinamide with aldehydes and ketones. The Journal of Organic Chemistry. 1999; 64 :1278-1284 - 22.
Chakraborti AK, Bhagat S, Rudrawar S. Magnesium perchlorate as an efficient catalyst for the synthesis of imines and phenylhydrazones. Tetrahedron Letters. 2004; 45 :7641-7644 - 23.
Panneerselvam P, Nair RR, Vijayalakshmi G, Subramanian EH, Sridhar SK. Synthesis of Schiff bases of 4-(4aminophenyl)-morpholine as potential antimicrobial agents. European Journal of Medicinal Chemistry. 2005; 40 :225-229 - 24.
Dalpozzo R, de Nino A, Nardi M, Russo B, Procopio A. Erbium(III) triflate: A valuable catalyst for the synthesis of aldimines, ketimines and enaminones. Synthesis. 2006; 7 :1127-1132 - 25.
Naeimi H, Salimi F, Rabiei K. Mild and convenient one pot synthesis of Schiff bases in the presence of P2O5/Al2O3 as new catalyst under solvent-free conditions. Journal of Molecular Catalysis A: Chemical. 2006; 260 :100-104 - 26.
Qin W, Long S, Panunzio M, Biondi S. Review Schiff Bases: A short survey on an evergreen chemistry tool. Molecules. 2013; 18 :12264-12289 - 27.
Varma RS, Dahiya R, Kumar S. Clay catalyzed synthesis of imines and enamines under solvent-free conditions using microwave irradiation. Tetrahedron Letters. 1997; 38 :2039-2042 - 28.
Schmeyers J, Toda F, Boy J, Kaupp G. Quantitative solid–solid synthesis of azomethines. Journal of Chemical Society. 1998; 4 :989-994 - 29.
Vass A, Duda SJ, Varma RS. Solvent-free synthesis of Nsulfonylimines using microwave irradiation. Tetrahedron Letters. 1999; 40 :4951-4954 - 30.
Tanaka K, Shiraishi R. Clean and efficient condensation reactions of aldehydes and amines in a water suspension medium. Green Chemistry. 2000; 2 :272-273 - 31.
Andrade CKZ, Takada SCS, Alves LM, Rodrigues JP, Suarez PAZ, Brandão RF, et al. Molecular sieves in ionic liquids as an efficient and recyclable medium for the synthesis of imines. Synlett. 2004; 12 :2135-2138 - 32.
Vázquez MÁ, Landa M, Reyes L, Miranda R, Tamariz J, Delgado F. Infrared irradiation: Effective promoter in the formation of N-benzylideneanilines in the absence of solvent. Synthetic Communications. 2004; 34 :2705-2718 - 33.
Gopalakrishnan M, Sureshkumar P, Kanagarajan V, Thanusu J. New environmentally-friendly solvent-free synthesis of imines using calcium oxide under microwave irradiation. Research on Chemical Intermediates. 2007; 33 :541-548 - 34.
Guzen KP, Guarezemini AS, Órfão ATG, Cella R, Pereira CMP, Stefani HA. Eco-friendly synthesis of imines by ultrasound irradiation. Tetrahedron Letters. 2007; 48 :1845-1848 - 35.
Houben J, Fischer W. Formation of aromatic nitriles by basic hydrolysis of trichloromethyl aryl ketimines. Acidic hydrolysis yields ketones. Journal für Praktische Chemie. 1929; 123 :262-313 - 36.
Shiraishi Y, Ikeda M, Tsukamoto D, Tanaka S, Hirai T. One-pot synthesis of imines from alcohols and amines with TiO2 loading Pt nanoparticles under UV irradiation. Chemical Communications. 2011; 47 :4811-4813 - 37.
Jiang L, Jin L, Tian H, Yuan X, Yu X, Xu Q. Direct and mild palladium-catalyzed aerobic oxidative synthesis of imines from alcohols and amines under ambient conditions. Chemical Communications. 2011; 47 :10833-10835 - 38.
Huang B, Tian H, Lin S, Xie M, Yu X, Xu Q. Cu(I)/TEMPO-catalyzed aerobic oxidative synthesis of imines directly from primary and secondary amines under ambient and neat conditions. Tetrahedron Letters. 2013; 54 :2861-2864 - 39.
Soule JF, Miyamura H, Kobayashi S. Selective imine formation from alcohols and amines catalyzed by polymer incarcerated gold/palladium alloy nanoparticles with molecular oxygen as an oxidant. Chemical Communications. 2013; 49 :355-357 - 40.
Gnanaprakasam B, Zhang J, Milstein D. Direct synthesis of imines from alcohols and amines with liberation of H2. Angewandte Chemie, International Edition. 2010; 49 :1468-1471 - 41.
Yuan H, Yoo WJ, Miyamura H, Kobayashi S. Discovery of a metalloenzyme-like cooperative catalytic system of metal nanoclusters and catechol derivatives for the aerobic oxidation of amines. Journal of the American Chemical Society. 2012; 134 :13970-13973 - 42.
Largeron M, Fleury MB. Bioinspired oxidation catalysts. Science. 2013; 339 :43-44 - 43.
Lan YS, Liao BS, Liu YH, Peng SM, Liu ST. Preparation of imines by oxidative coupling of benzyl alcohols with amines catalysed by dicopper complexes. European Journal of Organic Chemistry. 2013; 23 :5160-5164 - 44.
Largeron M. Protocols for the catalytic oxidation of primary amines to imines. European Journal of Organic Chemistry. 2013; 24 :5225-5235 - 45.
Yang CJ, Jenekhe SA. Conjugated aromatic polyimines. 2. Synthesis, structure, and properties of new aromatic polyazomethines. Macromolecules. 1995; 28 (4):1180-1196 - 46.
Morgan PW, Kwolek SL, Pletcher TC. Aromatic azomethine polymers and fibers. Macromolecules. 1987; 20 (4):729-739 - 47.
Destri S, Porzio W, Dubitsky Y. Design preparation and properties of regularly alternating conjugated low molecular weight copolymers based on thienylene-azomethine moietics. Synthetic Metals. 1995; 75 (1):25-36 - 48.
Yang HH. Aromatic High-strength Fibers. New York: Wiley-Interscience; 1989 - 49.
Cerrada P, Oriol L, Piñol M, Serrano JL, Alonso PJ, Puértolas JA, et al. Influence of hydroxy functionalization and metal cross-linking on fiber properties of liquid-crystalline polyazomethines. Macromolecules. 1999; 32 :3565-3573 - 50.
Ogiri S, Ikeda M, Kanazawa A, Shiono T, Ikeda T. Polymerization of liquid-crystalline monomers having a Schiff-base structure. Polymer. 1999; 40 :2145-2150 - 51.
Thomas O, Inganas O, Anderson MR. Synthesis and properties of a soluble conjugated poly(azomethine) with high molecular weight. Macromolecules. 1998; 31 (8):2676-2678 - 52.
Weaver MS, Bradley DDC. Organic electroluminescence devices fabricated with chemical vapour deposited polyazomethine films. Synthetic Metals. 1996; 83 :61-66 - 53.
Catanescu O, Grigoras M, Colotin G, Dobreanu A, Hurduc N, Simionescu CI. Synthesis and Characterization of Some Alifatik-aromatic Poly(Schiff base)s. European Polymer Journal. 2001; 37 :2213-2216 - 54.
March J. Advanced Organic Chemistry. NY, USA: Wiley; 1972 - 55.
Öztürk NS. Synthesis Schiff Bases Derived from Some Anilines and Different Pyridine Aldehydes and Preparing Their Some Transition Metal Complexes. İstanbul: İstanbul University; 1998 - 56.
Ancin N, İde S, Özta SG, Tüzün M. Spectral and structural studies of Ni(II) and Zn(II) Complexes of N-Trans-Cinnamylidene-2-Mercaptoaniline. Journal of Molecular Structure. 2002; 606 :45-50 - 57.
Fernández-G JM, del Rio-Portillo F, Quiroz-García B, Toscano RA, Salcedo R. The structures of some orto-hydroxy Schiff Base ligands. Journal of Molecular Structure. 2001; 561 :197-207 - 58.
Krygowski TM, Woźniak K, Anulewicz R, Pawlak D, Kolodziejski W, Grech E, et al. Through-resonance ionic hydrogen bonding in 5-nitro-nsalicylideneethylamine. The Journal of Physical Chemistry. A. 1997; 101 :9399-9404 - 59.
Metzler CM, Cahill A, Metzler DE. Equilibriums and absorption spectra of Schiff bases. Journal of the American Chemical Society. 1980; 102 (19):6075-6082 - 60.
Helmut S. Metal Ions in Biological Systems. New York and Basel: CRC Press; 1979. p. 304 - 61.
Sahal H. Synthesis and Characterization of N-O Type Schiff Base Ligands and Investigation of Their Transition Metal Complexes. Elazığ: Fırat University; 2011 - 62.
Naik KHK, Selvaraj S, Naik N. Metal complexes of ONO donor Schiff base ligand as a new class of bioactive compounds; Synthesis, characterization and biological evolution. Spectrochimica Acta Part A. 2014; 131 :599-605 - 63.
Syamal A, Singhal OP. Synthesis and characterization of new dioxouranium(VI) complexes with tridentate sulfur donor ligands. Journal of Inorganic and Nuclear Chemistry. 1981; 43 (11):2821-2825 - 64.
Saydam S, Yılmaz E. Synthesis, characterization, and thermal behavior of 4- Chloromethyl-2-(2-Hydroxynaphthylidenehydrazino) Thiazole and its Complexes with Cr(III), Co(II), Ni(II), and Cu(II). Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry. 2005; 35 (10):767-771 - 65.
Bialek M, Leksza A, Piechota A, Kurzak K, Koprek K. Oxovanadium(IV) complexes with [ONNO]-chelating ligands as catalysts for ethylene homo- and copolymerization. Journal of Polymer Research. 2014; 21 (4):389 - 66.
Baleizao C, Garcia H. Chiral Salen complexes: An overview to recoverable and reusable homogeneous and heterogeneous catalysts. Chemical Reviews. 2006; 106 :3987-4043 - 67.
Desai SB, Desai PB, Desai KR. Synthesis of some Schiff bases, thiazolidinones and azetidinones derived from 2,6-diaminobenzo1,2-d: 4,5-d’ bisthiazole and their anticancer activities. Heterocyclic Communications. 2001; 7 :83-90 - 68.
Przybylski P, Huczynski A, Pyta K, Brzezinski B, Bartl F. Biological properties of Schiff bases and azo derivatives of phenols. Current Organic Chemistry. 2009; 13 :124-148 - 69.
Abdel Aziz AA, Salem ANM, Sayed MA, Aboaly MM. Synthesis, structural characterization, thermal studies, catalytic efficiency and antimicrobial activity of some M(II) complexes with ONO tridentate Schiff base N-salicylidene-o-aminophenol (saphH2). Journal of Molecular Structure. 2012; 1010 :130-138 - 70.
Sinha D, Tiwari AK, Singh S, Shukla G, Mishra P, Chandra H, et al. Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde. European Journal of Medicinal Chemistry. 2008; 43 :160-165 - 71.
Ronad PM, Noolvi MN, Sapkal S, Dharbhamulla S, Maddi VS. Synthesis and antimicrobial activity of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives. European Journal of Medicinal Chemistry. 2010; 45 :85-89 - 72.
Amin R, Krammer B, Abdel-Kader N, Verwanger T, El-Ansary A. Antibacterial effect of some benzopyrone derivatives. European Journal of Medicinal Chemistry. 2010; 45 :372-378 - 73.
Karthikeyan MS, Prasad DJ, Poojary B, Bhat KS, Holla BS, Kumari NS. Synthesis and biological activity of Schiff and Mannich bases bearing 2,4-dichloro-5-fluorophenyl moiety. Bioorganic & Medicinal Chemistry. 2006; 14 :7482-7489 - 74.
Saravanan G, Pannerselvam P, Prakash CR. Synthesis and anti-microbial screening of novel Schiff bases of 3-amino-2-methyl quinazolin 4-(3H)-one. Journal of Advanced Pharmaceutical Technology & Research. 2010; 1 :320-325 - 75.
De Souza AO, Galetti FCS, Silva CL, Bicalho B, Parma MM, Fonseca SF, et al. Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Quimica Nova. 2007; 30 :1563-1566 - 76.
Rathelot P, Vanelle P, Gasquet M, Delmas F, Crozet MP, Timon-David P, et al. Synthesis of novel functionalized 5-nitroisoquinolines and evaluation of in vitro antimalarial activity. European Journal of Medicinal Chemistry. 1995; 30 :503-508 - 77.
Jarrahpour A, Khalili D, de Clercq E, Salmi C, Brunel JM. Synthesis, antibacterial, antifungal and antiviral activity evaluation of some new bis-Schiff bases of isatin and their derivatives. Molecules. 2007; 12 :1720-1730 - 78.
Snell EE, Jenkins WT. The mechanism of the transamination reaction. Journal of Cellular and Comparative Physiology. 1959; 54 :161-177 - 79.
Sharaby CM, Amine MF, Hamed AA. Synthesis, structure characterization and biological activity of selected metal complexes of sulfonamide Schiff base as a primary ligand and some mixed ligand complexes with glycine as a secondary ligand. Journal of Molecular Structure. 2017; 1134 :208-216 - 80.
Redshaw C. Use of metal catalysts bearing Schiff Base macrocycles for the ring opening polymerization (ROP) of cyclic esters. Catalysts. 2017; 7 (5):165-176 - 81.
Roberts DW, Schultz TW, Api AM. Skin sensitization QMM for HRIPT NOEL data: Aldehyde Schiff-Base domain. Chemical Research in Toxicology. 2017; 30 (6):1309 - 82.
DiRisio RJ, Armstrong JE, Frank MA, Lake WR, McNamara WR. Cobalt Schiff-base complexes for electrocatalytic hydrogen generation. Dalton Transactions. 2017; 46 :10418-10425 - 83.
Upadhyay KK, Kumar A, Upadhyay S, Mishra PC. Synthesis, characterization, structural optimization using density functional theory and superoxide ion scavenging activity of some Schiff bases. Journal of Molecular Structure. 2008; 873 :5-16 - 84.
Vigato PA, Tamburini S. The challenge of cyclic and acyclic Schiff bases and related derivatives. Coordination Chemistry Reviews. 2004; 248 (17-20):1717-2128 - 85.
Yeap GY, Ha ST, Ishizawa N, Suda K, Boey PL, Mahmood WAK. Synthesis, crystal structure and spectroscopic study of para substituted 2-hydroxy-3- methoxybenzalideneanilines. Journal of Molecular Structure. 2003; 658 (1-2):87-99 - 86.
Lasri J, Elsherbiny AS, Eltayeb NE, Haukka M, El-Hefnawy ME. Synthesis and characterization of ferrocene-based Schiff base and ferrocenecarboxaldehyde oxime and their adsorptive removal of methyl blue from aqueous solution. The Journal of Organic Chemistry. 2018; 866 :21-26 - 87.
Zeishen W, Zigi G, Zhenhuan Y. Synthesis, characterization and anticanser activity of L – alanin Schiff base complexes of cooper(II), zinc(II), an cobalt(II). Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry. 1990; 20 (3):335-344 - 88.
Zhang J, Xu L, Wong WY. Energy materials based on metal Schiff base complexes. Coordination Chemistry Reviews. 2018; 355 :180-198 - 89.
Kobayashi S, Mori Y, Fossey JS, Salter MM. Catalytic enantioselective formation of C−C bonds by addition to imines and hydrazones: A ten-year update. Chemical Reviews. 2011; 111 :2626-2704 - 90.
Guizzetti S, Benaglia M. Trichlorosilane-mediated stereoselective reduction of C=N bonds. European Journal of Organic Chemistry. 2010; 29 :5529-5541 - 91.
Masson G, Lalli C, Benohoud M, Dagousset G. Catalytic enantioselective [4 + 2] cycloaddition: A strategy to access aza-hexacycles. Chemical Society Reviews. 2013; 42 :902-923 - 92.
Smith CD, Gavrilyuk JI, Lough AJ, Batey RA. Lewis acid catalyzed three-component Hetero-Diels-Alder (Povarov) reaction of N-arylimines with strained norbornene-derived dienophiles. The Journal of Organic Chemistry. 2010; 75 :702-715 - 93.
Jørgensen KA. Catalytic asymmetric Hetero-Diels-Alder reactions of carbonyl compounds and imines. Angewate Chemie International Edition. 2000; 39 :3558-3588 - 94.
Cozzi PG. Metal-Salen Schiff base complexes in catalysis: Practical aspects. Chemical Society Reviews. 2004; 33 :410-421 - 95.
Katsuki T. Unique asymmetric catalysis of cis-beta metal complexes of salen and its related Schiff-base ligands. Chemical Society Reviews. 2004; 33 :437-444 - 96.
Matsunaga S, Shibasaki M. Multimetallic schiff base complexes as cooperative asymmetric catalysts. Synthesis. 2013; 45 :421-437 - 97.
D’hooghe M, van Brabandt W, Dekeukeleire S, Dejaegher Y, de Kimpe N. Highly stereoselective synthesis of beta-lactams utilizing alpha-chloroimines as new and powerful chiral inductors. Chemistry - A European Journal. 2008; 14 :6336-6340 - 98.
David O, Meester WJN, Bieraugel H, Schoemaker HE, Hiemstra H, van Maarseveen JH. Intramolecular staudinger ligation: A powerful ring-closure method to form medium-sized lactams. Angewandte Chemie, International Edition. 2003; 42 :4373-4375 - 99.
Palomo C, Aizpurua JM, Ganboa I, Oiarbide M. Asymmetric synthesis of beta-lactams through the Staudinger reaction and their use as building blocks of natural and nonnatural products. Current Medicinal Chemistry. 2004; 11 :1837-1872