What Is Imidazole?
Imidazole is a type of heterocyclic compound containing two nitrogen atoms. Other names include 1H-imidazole, glyoxane and 1,3-diazole,
Imidazole is also referred to as a generic term for a group of compounds with substituents on the nitrogen or carbon forming the imidazole ring.
Uses of Imidazole
Imidazole is widely used industrially as a raw material for chemicals, agrochemicals, and pharmaceuticals. In particular, it is often used as a semiconductor encapsulant and adhesive, as it exhibits excellent properties in areas around electronic substrates where heat resistance is required.
It is are also widely used in various other industrial fields, such as curing agents and accelerators for epoxy resins, urethane foaming catalysts, rust inhibitors, rubber vulcanization accelerators, paints, adhesives, construction materials, and sporting goods.
As a base catalyst type curing agent or accelerator, it is characterized by its excellent storage stability, such as curing with the addition of a relatively small amount.
In pharmaceutical applications, imidazole is used in antifungal agents, and imidazoles with substituents attached to the imidazole ring are also used in many pharmaceuticals, including anti-ulcer, anti-hypertensive, and anti-asthmatic agents. In addition, imidazolium salts containing imidazolium cations, which are quaternary amines formed by alkyl addition to the nitrogen of imidazole, have become ionic liquids, neutralized salts with melting points near room temperature, and are attracting attention as green solvents, which are environmentally friendly solvents.
Properties of Imidazole
Imidazole is a white to pale yellow flaky solid with molecular formula C3H4N2 and molecular weight of 68.08. It has a melting point of 88~92°C, a boiling point of 256°C, and a flash point of 145°C.
Imidazole is sublimable. It is soluble in solvents of high polarity, easily soluble in water, methanol, and ethanol, soluble in pyridine and chloroform, insoluble in ether and benzene of low polarity, and nearly insoluble in hexane.
It forms complexes with many transition metal ions and functions as an excellent ligand. It is resistant to thermal decomposition and relatively stable against oxidizing and reducing agents. It exhibits strong aromaticity and is susceptible to hydrogen atom substitution reactions.
Imidazole retains its symmetrical structure by taking on a resonance structure even when the proton at position 1 is removed or the nitrogen at position 3 is protonated. This allows the charge to be dispersed without loss of aromaticity.
Types of Imidazole
There are various derivatives with substituents attached to the imidazole ring, and these are called imidazoles. Substituents are attached to the nitrogen at the 1-position and the carbons at the 2-, 4-, and 5-positions, and it is possible to synthesize derivatives with different substituents at each position. The nitrogen at position 3 can also be cationized by nucleophilic substitution, but substituents can be attached.
Typical imidazoles include 2-methylimidazole, 2-ethyl-4-methylimidazole, and 2-phenylimidazole, where the prefix number indicates to which site of the ring the substituent is attached. Acylated imidazoles are sensitive to nucleophilic reactions and are used in the synthesis of carboxylic acid derivatives.
Imidazole is also commonly used as a base and catalyst in the protection of hydroxyl groups as silyl ethers by the action of silyl chlorides. Additionally, carbonyldiimidazoles (CDIs) are useful as carbonylating agents and amide condensing agents.
Other Information on Imidazole
How Imidazoles are Manufactured
Imidazole can be produced by the reaction of glyoxal with aldehydes and ammonia, or by synthesis from ethylenediamine and nitriles.
1. Synthesis from glyoxal
The type of aldehyde or amine used as a raw material determines the substituent at the 1- and 2-positions.
OHC-CHO + R1-NH2 + R2CHO → R1R2C3H2N2 + 3H2O
2. Synthesis from ethylenediamine
The substituent at the 1- and 2-positions is determined by the substituent of the nitrile.
H2N-CH2CH2-NH2 + RCN → R2C3H4N2 + NH3 → R2C3H2N2 + H2