1-Methylimidazole
[CAS# 616-47-7]

Identification

• Classification: Organic raw materials >> Heterocyclic compound
• Name: 1-Methylimidazole
• Synonyms: 1-Methyl-1H-imidazole; Methyl imidazole; N-Methylimidazole
• Molecular Formula: C₄H₆N₂
• Molecular Weight: 82.10
• CAS Registry Number: 616-47-7
• EC Number: 210-484-7
• SMILES: CN1C=CN=C1

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*, 1.031 g/mL (Expl.)
• Melting point: -60 °C (Expl.)
• Boiling point: 198.7±9.0 °C 760 mmHg (Calc.)^*, 195 - 197 °C (Expl.)
• Flash point: 92.2 °C (Calc.)^*, 92 °C (Expl.)
• Index of refraction: 1.525 (Calc.)^*, 1.495 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H302-H312:-H314:
• Safety Statements: P260-P264-P270-P280-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P354+P338-P316-P317-P321-P330-P362+P364-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	3	H311
Serious eye damage	Eye Dam.	1	H318
Reproductive toxicity	Repr.	2	H361d
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	3	H301
Reproductive toxicity	Repr.	2	H361
Flammable liquids	Flam. Liq.	4	H227

Discovery and Applications

1-Methylimidazole is an organic heterocyclic compound belonging to the imidazole family, characterized by a five-membered ring containing two nitrogen atoms at non-adjacent positions. The compound differs from imidazole by having a methyl group substituted at the nitrogen atom located at position 1 of the ring. Its molecular formula is C₄H₆N₂, and it appears as a colorless to pale yellow liquid with a pungent odor. 1-Methylimidazole has attracted significant attention due to its chemical properties and versatile applications in both academic research and industrial processes.

The compound was first prepared and characterized in the early 20th century as part of studies into heterocyclic nitrogen compounds. It is commonly synthesized through methylation of imidazole using methylating agents such as methyl iodide or dimethyl sulfate under controlled conditions. Alternative synthetic routes include condensation reactions involving glyoxal, formaldehyde, and methylamine derivatives.

1-Methylimidazole’s chemical structure imparts several distinctive properties. The methyl substitution on the nitrogen atom increases the compound’s nucleophilicity compared to unsubstituted imidazole, affecting its reactivity in various chemical processes. It also influences the compound’s basicity and coordination behavior, making it a valuable ligand in coordination chemistry.

One of the principal applications of 1-methylimidazole is as a catalyst and base in organic synthesis. It is frequently employed in nucleophilic substitution reactions, such as alkylations and acylations, and in processes involving esterification and transesterification. Its ability to act as a nucleophilic catalyst and its moderate basicity facilitate the activation of electrophilic substrates and stabilization of reaction intermediates, improving reaction rates and selectivity.

1-Methylimidazole is also widely used as a precursor or component in the synthesis of ionic liquids, particularly those based on imidazolium salts. Ionic liquids derived from 1-methylimidazole are notable for their low volatility, high thermal stability, and tunable physicochemical properties, which make them attractive solvents and electrolytes in green chemistry, catalysis, and electrochemical applications.

In coordination chemistry, 1-methylimidazole acts as a ligand capable of binding transition metals through the lone pair of electrons on the ring nitrogen atom not substituted by methyl. Complexes formed with metals such as copper, nickel, cobalt, and ruthenium have been studied extensively for their structural features and catalytic activities. These metal complexes find applications in catalysis, material science, and biological modeling.

Pharmacologically, derivatives of 1-methylimidazole and related imidazole compounds serve as building blocks for drugs and bioactive molecules. While 1-methylimidazole itself is primarily a chemical intermediate and reagent, its derivatives are involved in antifungal agents, histamine receptor antagonists, and enzyme inhibitors.

Physically, 1-methylimidazole has a boiling point around 198–200°C and is miscible with water and many organic solvents, facilitating its use in various reaction media. It is relatively stable under normal conditions but should be handled with care due to its irritant properties and pungent odor.

Analytical characterization of 1-methylimidazole includes nuclear magnetic resonance (NMR) spectroscopy, which confirms the presence and position of the methyl group and the imidazole ring protons. Infrared (IR) spectroscopy identifies characteristic ring vibrations and C–H stretching, while mass spectrometry (MS) provides molecular weight confirmation. Gas chromatography (GC) is used for purity analysis.

In industrial contexts, 1-methylimidazole is utilized in the manufacture of photographic chemicals, agrochemicals, dyes, and polymers. Its role as a base and nucleophilic catalyst makes it valuable in producing intermediates for pharmaceuticals and specialty chemicals.

Safety considerations for 1-methylimidazole include its irritant effect on skin, eyes, and respiratory tract. Proper ventilation and protective equipment are recommended during handling to prevent exposure. It is combustible and should be stored away from oxidizing agents and sources of ignition.

In summary, 1-methylimidazole is a versatile heterocyclic compound with significant utility as a catalyst, ligand, and chemical intermediate. Its methyl substitution enhances its reactivity relative to imidazole, broadening its applications in organic synthesis, coordination chemistry, and industrial manufacturing. The compound’s physicochemical properties and role in ionic liquid synthesis further contribute to its importance in contemporary chemical research and technology.

References

2006. Investigation of noncovalent complexes between β-cyclodextrin and polyamide acids containing N-methylpyrrole and N-methylimidazole by electrospray ionization mass spectrometry. Journal of The American Society for Mass Spectrometry, 17(1).
DOI: 10.1016/j.jasms.2005.08.011

2005. Kinetics of Ring Inversion in Strongly Nonplanar Iron(III) Octaalkyltetraphenylporphyrinates. Inorganic Chemistry, 44(6).
DOI: 10.1021/ic049090p

2005. New Insights into the Interactions of Serum Proteins with Bis(maltolato)oxovanadium(IV): Transport and Biotransformation of Insulin-Enhancing Vanadium Pharmaceuticals. Journal of the American Chemical Society, 127(11).
DOI: 10.1021/ja043944n