Schiff Bases

What is Schiff Base?

Schiff bases are condensation products of main amines with carbonyl compounds attaining significance day by day in the present scenario. Schiff bases are the compounds passing on imine or azomethine (– C=N–) functional groups and are known to be a flexible pharmacophore for the plan and improvement of different bioactive lead compounds. Schiff bases show valuable organic activities, for example, anti-inflammatory, pain-relieving, antimicrobial, anticonvulsant, antitubercular, anticancer, cancer prevention agent, anthelmintic, and antiglycation activities. Schiff bases are also appointed in the use of catalysts, pigments and dyes, intermediates in organic synthesis, polymer stabilizers, and corrosion inhibitors. The current review summarizes information on the diverse biological activities and also climaxes the recently synthesized several Schiff bases as potential bioactive cores.

Schiff's Base Reaction

The Schiff's base reaction is a group-specified reaction for aldehydes. The basic condition for the reaction to occur is a basic medium with aromatic amines to form a Schiff's base. Aniline is usually used to form a coloured anil or Schiff's base with an aldehyde. Carbohydrates can be envisioned with 4-aminobenzoic acid with the formation of coloured and fluorescent Schiff's bases. A very similar reaction takes place with 2-aminobiphenyl for aldehyde detection. One of the most subtle reagents for reducing sugar visualization, the aniline phthalate reagent, is also a Schiff's base reaction. The limit of sensitivity is 10 μg per chromatographic zone.

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Structure Schiff Base

A Schiff base is a multifaceted with the general structure R2C=NR‘ and is measured as subclasses of imines, being either subordinate aldehydes or secondary keto-amines reliant on their structure. The term is usually used as a synonym to azomethine (which refers to secondary aldimines). These compounds are named after the Italian chemist Hugo Schiff. Various systems exist for the nomenclature of these compounds.

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The general structure of a Schiff Base

Schiff bases are aldehyde- or ketone complexes where the carbonyl group is substituted by an azomethine or imine group. These are commonly used for industrial resolutions and also display a wide range of biological activities. These are the most extensively used organic compounds which are used as intermediates in organic synthesis, catalysts, pigments and dyes, polymer stabilizers, etc.

Synthesis of Schiff Bases

Schiff bases are characteristically formed by the condensation of a primary amine and an aldehyde which involves the usage of organic solvents such as methanol, tetrahydrofuran (THF), and 1,2-dichloroethane (DCE). Microwave-assisted preparation of a series of Schiff bases deprived of solvent has also been reported. Contrast of the three ways to synthesize simple Schiff base has been made and microwave irradiation was found to be the simplest way to synthesize the Schiff base.

Hydrolysis of Schiff Bases 

Schiff base (imine) formation and hydrolysis are highly significant in biological chemistry. Many enzymes employ imines as part of their reaction mechanisms. An important biological reaction is the formation of an imine bond between an amino acid carbonyl group and the amine of the amino acid lysine.

This is due to the reason of their high reactivity and the ability to form adducts with other molecules. An adduct is the product of two molecules (in this case, one of which is the imine) that results in a single species. This adduction allows the molecule to experience the reactive effect of the imine. Imines are reactive because of their ability to act as electron ‘sinks’.

The nitrogen of the C=N bond is readily protonated, yielding a protonated imine. This serves as an electron-accepting group, which, when present in an adduct, can pull electrons away from the bonds in the attached molecule. This facilitates bond cleavage, which is an essential part of many metabolic reactions, for example, in glycolysis and amino acid metabolism.

Another crucial feature of imines, which has fuelled their biological relevance, is their ability to tautomerism, arranging the position of their proton and double bond, which also facilitates bond cleavage.  The intermediate is called the iminium ion, and the resulting tautomer is called an enamine.  This allows for regeneration of the imine and subsequent release of the adduct following hydrolysis.

Applications of Schiff Bases

Antimalarial Activity

Malaria is a chronic disease which was neglected for many years. Every year, nearly 500 million people are affected by this disease and approximately 1-3 million people die among them. Schiff bases are proved to be a very good source for the design of antimalarial agents. Schiff Base 5 was the most effective antimalarial agent among the other synthesized bases.

Antibacterial Activity

Bacteria is the root cause of many infectious diseases and responsible for an increase in the mortality rate. There are different kinds of bacteria and they exhibit a lot of resistance to antibiotics. Schiff bases have emerged as promising antibacterial agents. For example, Mycobacterium can be effectively treated with N- (salicylidene) -2- hydroxyaniline.

Antifungal Activity

Schiff bases with a 2,4-dichloro-5-fluorophenyl moiety have been proven to restrict the growth of fungi like Aspergillus flavus, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei.

Schiff Base Complexes As Catalysts

Many Schiff base complexes of metal ions show high catalytic activity and play a significant role in various reactions to enhance their yield and product selectivity. The convenient route of synthesis and thermal stability of Schiff base ligands have contributed significantly for their possible applications in catalysis as metal complexes 

Schiff base complexes of transition metal ions are efficient catalysts for both homogeneous and heterogeneous reactions and the activity of these complexes varies with the type of ligands, coordination sites and metal ions. Chiral Schiff base complexes are more choosy in various reactions such as oxidation, hydroxylation, aldol condensation and epoxidation. 

FAQ (Frequently Asked Questions)

1. What is Schiff's Base Reaction? Which Amino Acid Can Form A Schiff Base?

The Schiff's base response is a group-specific response for aldehydes. The response, as a rule, happens under fundamental conditions with aromatic amines to frame a Schiff's base. Aniline is regularly used to shape a coloured anil or Schiff's base with an aldehyde.

Natural α-amino acids (glycine, l-alanine and l-leucine) were condensed with aromatic aldehydes (p-methylbenzaldehyde and p-ethylbenzaldehyde) to form Schiff bases in excellent yields (∼97%).

2. What is The Use of The Schiff Test And Why Does Glucose Not React With Schiff's Base?

Schiff reagent is used to detect the presence of aldehyde and ketonic groups. It consists of fuchsin dye decolourised by sulphurous acid. Immediate Red/pink colour appearance detects the presence of an aliphatic aldehyde. Aliphatic ketones and aromatic aldehydes take time and slowly pink colour blooms.

Glucose does not react with Schiff's reagent & 2,4DNP reagent although it has an aldehydic group. After the internal cyclisation, it forms either α-anomer.In these forms a free aldehydic group is not present. So,it does not give a reaction to the aldehyde group.