Imidazole
[CAS# 288-32-4]

Identification

• Classification: Chemical pesticide >> Fungicide >> Azole fungicide
• Name: Imidazole
• Synonyms: 1,3-Diazole; 1H-Imidazole; Glyoxaline
• Molecular Formula: C₃H₄N₂
• Molecular Weight: 68.08
• CAS Registry Number: 288-32-4
• EC Number: 206-019-2
• SMILES: C1=CN=CN1

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.03 g/mL (Expl.)
• Melting point: 88 - 91 °C (Expl.)
• Boiling point: 257.0±9.0 °C 760 mmHg (Calc.)^*, 256 °C (Expl.)
• Flash point: 145.0 °C (Calc.)^*, 145 °C (Expl.)
• Solubility: 10 mM (H2O) (Expl.)
• Index of refraction: 1.528 (Calc.)^*, 1.48 (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08 Danger
• Risk Statements: H302-H314:-H360D:
• Safety Statements: P203-P260-P264-P270-P280-P301+P317-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P318-P321-P330-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360
Skin corrosion	Skin Corr.	1C	H314
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1B	H314
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - single exposure	STOT SE	3	H336
Reproductive toxicity	Repr.	1B	H360D
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	3	H311
Reproductive toxicity	Repr.	1B	H361
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	2	H371
Skin corrosion	Skin Corr.	1A	H314
Reproductive toxicity	Repr.	1A	H360
Reproductive toxicity	Repr.	1B	H360D

• Transport Information: UN 1759

Discovery and Applications

Imidazole is a five-membered planar heteroaromatic compound composed of three carbon atoms and two nitrogen atoms at the 1 and 3 positions in the ring. Its molecular formula is C₃H₄N₂, and it has a molar mass of approximately 68.08 g/mol. Imidazole is an important basic building block in organic and biological chemistry due to its aromatic character, amphoteric nature, and ability to participate in hydrogen bonding and metal coordination.

Imidazole was first synthesized in the mid-19th century by Heinrich Debus in 1858, who discovered it during experiments involving glyoxal, ammonia, and formaldehyde. The synthesis, now known as the Debus synthesis, remains a foundational method for producing substituted imidazoles and was later refined by researchers such as James Moir and Arthur Hantzsch. The Hantzsch synthesis, which involves the condensation of 1,2-dicarbonyl compounds with aldehydes and ammonia or amines, is widely used in modern laboratories for the preparation of imidazole derivatives.

Imidazole is a colorless to pale yellow crystalline solid at room temperature and has a melting point of about 89-91 °C. It is highly soluble in water and polar organic solvents, making it useful in both aqueous and non-aqueous systems. The ring system is aromatic due to the presence of six delocalized π electrons, including a lone pair from the pyrrole-like nitrogen and the double bonds within the ring. One nitrogen atom is sp²-hybridized with a lone pair contributing to aromaticity (position 1), while the other nitrogen is similar to pyridine (position 3), bearing a lone pair that does not participate in aromaticity, making it available for protonation or hydrogen bonding.

Biologically, the imidazole ring is of great significance. It is a component of the amino acid histidine, which is essential for protein structure and enzyme function. In many metalloproteins and enzymes, the imidazole group of histidine acts as a ligand that coordinates metal ions such as Fe²⁺, Zn²⁺, or Cu²⁺, playing a critical role in catalysis, electron transfer, and structural stability. Histidine residues are also involved in acid-base catalysis due to the proton-donating and -accepting capabilities of the imidazole group.

Imidazole and its derivatives are widely used in pharmaceutical chemistry. Many antifungal drugs, including clotrimazole, ketoconazole, and miconazole, contain imidazole rings. These compounds typically inhibit fungal cytochrome P450 enzymes, disrupting ergosterol biosynthesis and compromising the integrity of fungal cell membranes. Imidazole-containing compounds are also used in the treatment of cancer, hypertension, and neurological disorders, due to their bioactive properties and structural versatility.

In synthetic chemistry, imidazole serves as a useful base and nucleophilic catalyst. It is commonly used in peptide coupling reactions, nucleoside chemistry, and the activation of carboxylic acids. The ring can be substituted at various positions, allowing for the development of tailored molecules for specific chemical or biological purposes. Methylation, halogenation, and alkylation reactions are frequently employed to modify the imidazole ring.

Imidazole derivatives are also employed in coordination chemistry and materials science. Due to the basic nature of the ring and its nitrogen lone pairs, imidazole readily forms complexes with transition metals. These complexes can be used in catalysis, molecular recognition, and the development of supramolecular assemblies.

From an analytical perspective, imidazole is identified and studied using techniques such as NMR spectroscopy, where the ring protons and nitrogen environments produce characteristic signals. Infrared spectroscopy detects the N-H stretch and ring vibrations, while mass spectrometry and elemental analysis confirm molecular weight and composition.

In conclusion, imidazole is a simple yet highly versatile heterocycle with broad applications in organic synthesis, medicinal chemistry, and biochemistry. Its aromaticity, hydrogen bonding potential, and coordination behavior make it essential in both natural and synthetic chemical systems.

References

2025. Colorimetric fluorescence of the 1,10-phenantholineyl-imidazole sensor probe for the selective detection of Zn2+ and Cd2+ ions. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 337.
DOI: 10.1016/j.saa.2024.125436

2025. Formation of amino acid-based imidazole salts considerably increased the determined level of fluorescent advanced glycation end products in biscuits. Food Chemistry, 469.
DOI: 10.1016/j.foodchem.2024.142227

2025. Direct and quantitative analysis of tRNA acylation using intact tRNA liquid chromatography-mass spectrometry. Nature Protocols, 20(1).
DOI: 10.1038/s41596-024-01086-9