Description
5-Chloro-1-methyl-4-nitroimidazole is an imidazole derivative. It is useful in the rapid mix experiments to investigate the mechanism of anomalous radiosensitization of mammalian cells. It can also be used in the synthesis of 5-aryl-1-methyl-4-nitroimidazoles, via Suzuki coupling with arylboronic acids, catalyzed by dichlorobis-(triphenylphosphine) palladium (II), K2CO3 and tetrabutylammonium bromide.
References
http://www.sigmaaldrich.com/catalog/product/aldrich/367532?lang=en®ion=US
Watts, M. E., et al. "Rapid-mix studies on the anomalous radiosensitization of mammalian cells by 5-chloro-1-methyl-4-nitromidazole." Int J Radiat Biol Relat Stud Phys Chem Med 38.6(1980):673-675.
Saadeh, H. A, I. M. Mosleh, and M. M. Elabadelah. "New synthesis and antiparasitic activity of model 5-aryl-1-methyl-4-nitroimidazoles. "Molecules 14.8(2009):2758-67.
Description
5-Chloro-1-methyl-4-nitroimidazole is an intermediate
in azathioprine synthesis, also present in the end
product. It induced contact dermatitis in a man
working on azathioprine synthesis. Cross reactivity is
possible with imidazoles tioconazole, and econazole.
Chemical Properties
White Solid
Uses
5-Chloro-1-methyl-4-nitroimidazole (CMNI) is suitable for use in the rapid mix experiments to investigate the mechanism of anomalous radiosensitization of mammalian cells by CMNI. It may be used in the synthesis of 5-aryl-1-methyl-4-nitroimidazoles, via Suzuki coupling with arylboronic acids, catalyzed by dichlorobis-(triphenylphosphine)palladium(II), K
2CO
3 and tetrabutylammonium bromide.
General Description
5-Chloro-1-methyl-4-nitroimidazole is an 4-nitroimidazole derivative.
Contact allergens
This intermediate in azathioprine synthesis is also present
in the end product. It induced contact dermatitis in
a man working on azathioprine synthesis. Cross-reactivity
is possible with imidazoles tioconazole and
econazole.
Synthesis
General procedure for the synthesis of 5-chloro-1-methyl-4-nitroimidazole from 5-chloro-1-methylimidazole: A mixed solution of 1-methyl-5-chloroimidazole (57.0 g, 0.50 mol) and dilute nitric acid (690 mL, 1.15 mol) was concentrated to dryness. The resulting light yellow oil (131.40 g) was slowly added dropwise to 214 mL of pre-cooled concentrated sulfuric acid over 85 minutes under nitrogen protection. Subsequently, the reaction mixture was stirred at 100 °C for 2 h under nitrogen atmosphere. Upon completion of the reaction, the reaction solution was slowly poured into 21 mL of ice water and precipitate was precipitated and collected by filtration. The precipitate was washed to neutrality with ice water to give 1-methyl-5-chloro-4-nitroimidazole (45.3 g, 62% yield) in white crystalline form. The melting point of the product was 147.5-148.9 °C. 1H NMR (400 MHz, d6-DMSO): δ= 7.50 (s, 1H, 2-H), 3.72 (s, 3H, CH3). 13C NMR (100 MHz, d6-DMSO): δ= 142.4 (C-4), 134.6 (C-2), 119.6 (C-5). 32.9 (CH3).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1369 - 1375
[2] Patent: US2017/281501, 2017, A1. Location in patent: Paragraph 0277-0280
[3] Journal of Medicinal Chemistry, 1996, vol. 39, # 14, p. 2690 - 2695
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 5, p. 1440 - 1444
[5] Patent: EP1066286, 2009, B1. Location in patent: Page/Page column 39-40
