1-Methylimidazole or N-methylimidazole is an aromatic heterocyclic organic compound with the formula CH3C3H3N2. It is a colourless liquid that is used as a specialty solvent, a base, and as a precursor to some ionic liquids. It is a fundamental nitrogen heterocycle and as such mimics for various nucleoside bases as well as histidine and histamine.
With the N-methyl group, this particular derivative of imidazole cannot tautomerize. It is slightly more basic than imidazole, as indicated by the pKa's of the conjugate acids of 7.0 and 7.4.[1] Methylation also provides a significantly lower melting point, which makes 1-methylimidazole a useful solvent.
1-Methylimidazole is prepared mainly by two routes industrially. The main one is acid-catalysed methylation of imidazole by methanol. The second method involves the Radziszewski reaction from glyoxal, formaldehyde, and a mixture of ammonia and methylamine.[2]
(CHO)2 + CH2O + CH3NH2 + NH3 → H2C2N(NCH3)CH + 3 H2O
The compound can be synthesized on a laboratory scale by methylation of imidazole at the pyridine-like nitrogen and subsequent deprotonation.[3] Similarly, 1-methylimidazole may be synthesized by first deprotonating imidazole to form a sodium salt followed by methylation.[4] [5]
H2C2N(NH)CH + CH3I → [H<sub>2</sub>C<sub>2</sub>(NH)(NCH<sub>3</sub>)CH]I
[H<sub>2</sub>C<sub>2</sub>(NH)(NCH<sub>3</sub>)CH]I + NaOH → H2C2N(NCH3)CH + H2O + NaI
In the research laboratory, 1-methylimidazole and related derivatives have been used as mimic aspects of diverse imidazole-based biomolecules.
1-Methylimidazole is also the precursor for the synthesis of the methylimidazole monomer of pyrrole-imidazole polyamides. These polymers can selectively bind specific sequences of double-stranded DNA by intercalating in a sequence dependent manner.[6]
1-Methylimidazole alkylates to form dialkyl imidazolium salts. Depending on the alkylating agent and the counteranion, various ionic liquids result, e.g. 1-butyl-3-methylimidazolium hexafluorophosphate ("BMIMPF6"):[7]
BASF has used 1-methylimidazole as a means to remove acid during their industrial-scale production of diethoxyphenylphosphine. In this biphasic acid scavenging using ionic liquids (BASIL) process, 1-methylimidazole reacts with HCl to produce 1-methylimidazolium hydrochloride, which spontaneously separates as a separate liquid phase under the reaction conditions.[7] [8]
2 MeC3N2H3 + C6H5PCl2 + 2 C2H5OH → 2 [MeC<sub>3</sub>N<sub>2</sub>H<sub>4</sub>]Cl + C6H5P(OC2H5)2
1-methylimidazole (NMIz) as a ligand forms octahedral ions M(NMIz)62+with M = Fe, Co, Ni, and a square-planar ion Cu(NMIz)42+. [9] 1-methylimidazole forms adducts with Lewis acids such as molybdenum perfluorobutyrate and [Rh(CO)<sub>2</sub>Cl]2. The donor properties of 1-methylimidazole have been analyzed by the ECW model yielding EB= 1.16 and CB= 4.92.