Formation, Properties & Applications of 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.
FAQs on Schiff Bases: Complete Chemistry Guide
1. What is a Schiff base and how is it typically formed?
A Schiff base is a type of organic compound containing a carbon-nitrogen double bond (C=N), where the nitrogen atom is connected to an aryl or alkyl group, but not hydrogen. They are also commonly known as imines. They are typically formed through a nucleophilic addition-elimination reaction between a primary amine (R-NH₂) and an aldehyde or a ketone under specific conditions, usually with mild acid catalysis.
2. What is the general reaction for the preparation of a Schiff base?
The preparation of a Schiff base involves the condensation reaction of a carbonyl compound (an aldehyde or ketone) with a primary amine. The reaction proceeds in two main steps: first, the amine acts as a nucleophile, attacking the electrophilic carbonyl carbon to form a carbinolamine intermediate. Second, this unstable intermediate undergoes dehydration (loss of a water molecule) to form the stable C=N double bond of the Schiff base. The general equation is: R₂C=O + R'NH₂ ⇌ R₂C=NR' + H₂O.
3. Why is an acid catalyst often required for Schiff base formation?
An acid catalyst plays a crucial dual role in the formation of a Schiff base. Its primary function is to protonate the hydroxyl group (-OH) of the carbinolamine intermediate, turning it into a better leaving group (-OH₂⁺). This facilitates the final elimination of a water molecule to form the stable imine. However, the pH must be carefully controlled; if the solution is too acidic, it will protonate the starting amine, making it non-nucleophilic and stopping the initial attack on the carbonyl group.
4. What are some important applications of Schiff bases in chemistry and biology?
Schiff bases have diverse applications across various fields. Key examples include:
- Analytical Chemistry: Used in the Schiff test to detect the presence of aldehydes.
- Organic Synthesis: They are important intermediates for synthesising various organic compounds, including amino acids.
- Biochemistry: The formation of Schiff bases is a key step in several enzymatic reactions, such as in transamination and the mechanism of vision, where retinal forms a Schiff base with the protein opsin.
- Coordination Chemistry: They act as versatile ligands to form stable complexes with a wide range of metal ions, which have catalytic and medicinal properties.
5. What is the Schiff's test, and why doesn't glucose give a positive result despite having an aldehyde group?
The Schiff's test uses Schiff's reagent (decolourised fuchsin dye) to detect the presence of aldehydes, which restore the reagent's pink or magenta colour. Although glucose has an aldehyde functional group in its open-chain form, it primarily exists as a stable cyclic hemiacetal in solution. In this cyclic structure, the aldehyde group is not free to react with the Schiff's reagent. The equilibrium concentration of the open-chain form is too low to produce a visible, positive result.
6. How does a Schiff base (imine) differ from an enamine?
The key difference lies in the type of amine used for their formation and the resulting structure.
- Schiff Base (Imine): Forms from the reaction of an aldehyde or ketone with a primary amine (R-NH₂). The characteristic feature is a carbon-nitrogen double bond (C=N).
- Enamine: Forms from the reaction of an aldehyde or ketone with a secondary amine (R₂NH). The structure is characterised by a nitrogen atom bonded to a carbon-carbon double bond (C=C-N).
7. Can ketones form Schiff bases as readily as aldehydes? Explain why.
No, ketones generally form Schiff bases less readily than aldehydes. There are two main reasons for this difference in reactivity:
- Steric Hindrance: Ketones have two alkyl or aryl groups attached to the carbonyl carbon, which creates more steric bulk compared to aldehydes, which have only one such group and a small hydrogen atom. This bulk hinders the initial nucleophilic attack by the amine.
- Electronic Effects: The two alkyl groups on a ketone are electron-donating, which reduces the partial positive charge (electrophilicity) on the carbonyl carbon, making it a less attractive target for the nucleophilic amine.
