4-Methylimidazole
[CAS# 822-36-6]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: 4-Methylimidazole
• Synonyms: 4-Methyl-1H-imidazole
• Molecular Formula: C₄H₆N₂
• Molecular Weight: 82.10
• CAS Registry Number: 822-36-6
• EC Number: 212-497-3
• SMILES: CC1=CN=CN1

Properties

• Density: 1.02
• Melting point: 46-48 °C
• Boiling point: 263 °C
• Flash point: 157 °C

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07;GHS08 Danger
• Risk Statements: H302-H311-H312-H314-H315-H317-H318-H319-H3331-H335-H336-H351
• Safety Statements: P203-P260-P261-P262-P264-P264+P265-P270-P271-P272-P280-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P318-P319-P321-P330-P332+P317-P333+P317-P337+P317-P361+P364-P362+P364-P363-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1B	H314
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	3	H311
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H336
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H331
Skin corrosion	Skin Corr.	1	H314
Skin sensitization	Skin Sens.	1	H317
Skin corrosion	Skin Corr.	1A	H314
Skin sensitization	Skin Sens.	1B	H317
Skin corrosion	Skin Corr.	1C	H314
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

Discovery and Applications

4-Methylimidazole, with the chemical formula C₄H₆N₂, is an organic compound featuring a methyl group attached to the 4-position of the imidazole ring. This compound is a derivative of imidazole, a five-membered heterocyclic ring containing two nitrogen atoms.

The discovery of 4-methylimidazole dates back to the early 20th century, following the initial studies of imidazole and its derivatives. Imidazole itself was first synthesized by the German chemist Heinrich Debus in 1858. As research advanced, various substituents were introduced to the imidazole ring, leading to the identification of 4-methylimidazole. Its synthesis typically involves the methylation of imidazole or the reaction of 4-hydroxyimidazole with methylating agents.

4-Methylimidazole is used in several industrial and research applications due to its chemical properties. One of its primary applications is as a key intermediate in the synthesis of pharmaceuticals and agrochemicals. It is involved in the production of various biologically active compounds, including antifungal agents and enzyme inhibitors. For instance, 4-methylimidazole is used in the synthesis of the antifungal drug clotrimazole, which is effective against a range of fungal infections.

In the food industry, 4-methylimidazole is notably used as a component of caramel colorings, particularly in the production of caramel color IV, which is used to color soft drinks, sauces, and other food products. However, its presence in food products has raised health concerns due to its potential carcinogenic properties when consumed in large amounts. Regulatory agencies have established limits on its concentration in food to ensure consumer safety.

The compound is also utilized in scientific research, particularly in the study of imidazole-based compounds and their interactions with biological systems. It serves as a model compound for investigating the effects of imidazole derivatives on enzyme activity and protein interactions. Additionally, 4-methylimidazole's role as a ligand in coordination chemistry has been explored, where it forms complexes with various metal ions, contributing to studies in catalysis and materials science.

Overall, 4-methylimidazole's versatility and its role in both industrial applications and research underscore its importance in various fields of chemistry and manufacturing.

References

2024. 4-methylimidazole exposure impairs sperm mobility by reducing the expression of blood-testis barrier junction protein in mouse testes. Reproductive Biology, 24(3).
DOI: 10.1016/j.repbio.2024.100928

2023. Investigation on the simultaneous inhibition of advanced glycation end products, 4-methylimidazole and hydroxymethylfurfural in thermal reaction meat flavorings by liquiritigenin, liquiritin and glycyrrhizic acid and its possible pathways. Food research international (Ottawa, Ont.), 173(2).
DOI: 10.1016/j.foodres.2023.113414

2024. Safety assessment of three common food additives: the reproductive, oxidative and enzymatic perspective. Discover Toxicology, 2(1).
DOI: 10.1007/s44339-024-00007-5