1-Methylimidazole

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.

1-Methylimidazole

Names
Preferred IUPAC name 1-Methyl-1H-imidazole
Other names 1-Methylimidazole N-Methylimidazole NMI
Identifiers
CAS Number	616-47-7 Y
3D model (JSmol)	Interactive image Interactive image
Beilstein Reference	105197
ChEBI	CHEBI:113454 Y
ChEMBL	ChEMBL543 Y
ChemSpider	1348 Y
DrugBank	DB02671
ECHA InfoCard	100.009.532
EC Number	210-484-7
Gmelin Reference	2403
PubChem CID	1390
UNII	P4617QS63Y
CompTox Dashboard (EPA)	DTXSID6052291
InChI InChI=1S/C4H6N2/c1-6-3-2-5-4-6/h2-4H,1H3 Y Key: MCTWTZJPVLRJOU-UHFFFAOYSA-N Y InChI=1/C4H6N2/c1-6-3-2-5-4-6/h2-4H,1H3 Key: MCTWTZJPVLRJOU-UHFFFAOYAU
SMILES n1ccn(c1)C Cn1ccnc1
Properties
Chemical formula	C4H6N2
Molar mass	82.10 g/mol
Density	1.03 g/cm3
Melting point	−6 °C (21 °F; 267 K)
Boiling point	198 °C (388 °F; 471 K)
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H302, H312, H314
Precautionary statements	P260, P264, P270, P280, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P322, P330, P363, P405, P501
Safety data sheet (SDS)	Oxford MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Basicity

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.

Synthesis

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][3]

(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.^[4] Similarly, 1-methylimidazole may be synthesized by first deprotonating imidazole to form a sodium salt followed by methylation.^[5][6]

H₂C₂N(NH)CH + CH₃I → [H₂C₂(NH)(NCH₃)CH]I

[H₂C₂(NH)(NCH₃)CH]I + NaOH → H₂C₂N(NCH₃)CH + H₂O + NaI

Applications

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.^[7]

Ionic liquid precursor

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"):^[8][9]

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.^[8][10]

2 MeC₃N₂H₃ + C₆H₅PCl₂ + 2 C₂H₅OH → 2 [MeC₃N₂H₄]Cl + C₆H₅P(OC₂H₅)₂

Donor properties

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⁺.^[11] 1-methylimidazole forms adducts with Lewis acids such as molybdenum perfluorobutyrate and [Rh(CO)₂Cl]₂. The donor properties of 1-methylimidazole have been analyzed by the ECW model yielding E_B= 1.16 and C_B= 4.92.

See also

• 4-Methylimidazole