1-Methylimidazole

1-Methylimidazole
IUPAC name 1-Methylimidazole
Other names N-Methylimidazole
Identifiers
CAS number	616-47-7 Y
ChemSpider	1348 Y
ChEBI	CHEBI:113454 N
ChEMBL	CHEMBL543 N
Jmol-3D images	Image 1 Image 2
SMILES n1ccn(c1)C Cn1ccnc1
InChI InChI=1S/C4H6N2/c1-6-3-2-5-4-6/h2-4H,1H3 N Key: MCTWTZJPVLRJOU-UHFFFAOYSA-N N InChI=1/C4H6N2/c1-6-3-2-5-4-6/h2-4H,1H3 Key: MCTWTZJPVLRJOU-UHFFFAOYAU
Properties
Molecular formula	C4H6N2
Molar mass	82.10 g/mol
Density	1.03 g/cm³
Melting point	-60 °C
Boiling point	198 °C
Hazards
MSDS	Oxford MSDS
EU classification	Harmful (Xn); Corrosive (C)
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

1-Methylimidazole or N-Methylimidazole is an aromatic heterocyclic organic compound with the formula CH₃C₃H₃N₂. Its N-methylation removes the possibility of tautomerization, which occurs in imidazole and many imidazole derivatives. 1-Methylimidazole maintains the pyridine-like nitrogen of imidazole, only with a slightly higher pKa.^[1] The methylation also provides a significantly lower melting point, which makes 1-methylimidazole a useful solvent.

1-Methylimidazole has found use as a solvent, a base, a catalyst, a mimic for purine nucleoside bases and histidine and histamine, and as an ionic liquid precursor.

Synthesis

1-Methylimidazole is synthesized on an industrial scale by the Radziszewski reaction from glyoxal, formaldehyde, and a mixture of ammonia and methylamine.^[2][3]

The compound can also 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]

Biomolecule analog

The imidazole backbone is an essential functional unit in biology. The amino acid histidine, the signaling molecule histamine, and the purine nucleobases all contain an imidazole ring.^[2]

1-Methylimidazole and its derivatives have been used to mimic aspects of these biomolecules. These mimics can be useful in studies to elucidate biological mechanisms and as portions of synthetic bioactive molecules.

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 chloride, a salt that is easily separated and deprotonated to regenerate 1-methylimidazole.^[8]

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

References

1. ^ Albert, A., Heterocyclic Chemistry, 2nd ed.; 1968 Athlone Press, ISBN 048511092X
2. ^ ^{a b} Ebel, K., Koehler, H., Gamer, A. O., & Jäckh, R. “Imidazole and Derivatives.” In Ullmann’s Encyclopedia of Industrial Chemistry; 2002 Wiley-VCH, doi:10.1002/14356007.a13_661
3. ^ Bronislas Radziszewski (1882). "Ueber die Constitution des Lophins und verwandter Verbindungen". Berichte der deutschen chemischen Gesellschaft 15 (2): 1493–1496. doi:10.1002/cber.18820150207. 
4. ^ Gilchrist, T. L., Heterocyclic Chemistry, 2nd ed.; 1992 Longman Scientific & Technical, ISBN 0-582-06420-1
5. ^ Grimmett, M. R., Imidazole and Benzimidazole Synthesis; 1997 Academic Press, ISBN 0-12-303190-7
6. ^ Gupta, R. R., Kumar, M., Gupta, V., Heterocyclic Chemistry II: Five Membered Heterocycles; 1999 Springer, ISBN 3-540-65252-3
7. ^ Baird, E.E. & Dervan, P.B. J. Am. Chem. Soc. 118 (26), 6141-6146, 1996.
8. ^ ^{a b} Meindersma, W., Maase, M., and De Haan, A. B. “Ionic Liquids.” In Ullmann’s Encyclopedia of Industrial Chemistry; 2007 Wiley-VCH, doi:10.1002/14356007.l14_l01
9. ^ Dupont, J., Consorti, C., Suarez, P., de Souza, R. (2004), "Preparation of 1-Butyl-3-methyl imidazolium-based Room Temperature Ionic Liquids", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v79p0236 ; Coll. Vol. 10: 184