2- Methyl-4-nitroimidazole

It is then extracted with chloroform (1,000 cc) and, after evaporation of the chloroform in vacuo, there is obtained a pasty mass (77 g) which is recrystallized from ethyl acetate (450 cc) in the presence of animal charcoal. There is thus obtained 1-(2-hvdroxvethyl)-2-methyl-5-nitroimidazole (24 g) as a creamy white crystalline powder melting at 158° to 160°C. 

The solution obtained is treated with ammonium hydroxide (d = 0.92 106 cc), saturated with sodium chloride, and then extracted with ethyl acetate (total 660 cc). The combined organic extracts are washed with a saturated aqueous sodium chloride solution (60 cc) and then dried over sodium sulfate. The volatile products are evaporated under reduced pressure (20 mm Hg) and a mixture of 1-(2-acetoxypropyl)-2-methyl-4-nltrolmidazole and 1-(2-acetoxypropyl)-2-methyl-5-nitroimidazole (18.6 g) is obtained in the form of a red oil. 

Chemical Name 1-[2-(ethylsulfonyl)ethyl] -2-methyl-5-nitroimidazole Common Name —... 

Ethyl sulfonyl ethanol p-Toluenesulfonyl chloride 2-Methyl-5-nitroimidazole... 

Epoxypropyl)-2-methyl-5-nitroimidazole Ornidazole Ergocryptine Bromocriptine Erythromycin... 

C H,, N203 85660-33-9) see Nomifensine 7V-methyl-lV-(2-nitrobenzyl)phenacylamine (C (,H 9N203 102436-67-9) see Nomifensine 2-methyl-5-nitro-4,6-dihydroxypyrimidine (C5H5N3O4 53925-27-2) see Moxonidine 2-methyl-5-nitroimidazole... 

Metronidazole Metronidazole, 2-methyl-5-nitroimidazol-l-ethanol (37.2.10), is made by nitrating 2-methylimidazole to make 2-methyl-5-nitroimidazole (37.2.9), which is then reacted with 2-chloroethanol or ethylenoxide, which is easily transformed to the desired metronidazole [49,50]. 

Tinidazole Tinidazole, l-2-(ethylsnlfonyl)ethyl-2-methyl-5-nitroimidazole (37.2.12), is also made from 2-methyl-5-nitroimidazole (37.2.9), which npon being reacted with 2-ethoxysnlfonyl-p-tolnenesnlfonate (37.2.11) transformed into the desired tinidazole. 

Fig-1 Metronidazole, l-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, and side chains in positions 1 and 2 of related compounds tinidazole and ornidazole. Metronidazole and tinidazole are approved by the FDA for treatment of trichomoniasis, and ornidazole is used for this purpose outside the USA. Both tinidazole and ornidazole have been used with variable success in attempts to cure metronidazole-resistant infections... 

Methyl-4(or 5)-nitroimidazole (127 g) is heated with ethylene chlorohydrin (795 g) for 18 hours at 128° to 130°C and the chlorohydrin (660 g) is then distilled under reduced pressure (30mm Hg). The residue is treated with water (300 cc) and filtered, and the filtrate is made alkaline by the addition of sodium hydroxide solution (d = 1.33, 100 cc). It is then extracted with chloroform (1,000 cc) and, after evaporation of the chloroform in vacuo, there is obtained a pasty mass (77 g) which is recrystallized from ethyl acetate (450 cc) in the presence of animal charcoal. There is thus obtained l-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (24 g) as a creamy white crystalline powder melting at 158° to 160°C. 

This oil (5.8 g) is dissolved in methyl ethyl ketone (20 cc) and chromatographed over silica (232 g) contained in a column 45 cm in diameter. The column is eluted with methyl ethyl ketone the first 600 cc of eluate are discarded and 500 cc of eluate are then collected and concentrated under reduced pressure (25 mm Hg) a partially crystalline product (2.4 g) is thus obtained. l-(2-Hydroxypropyl)-2-methyl-5-nitroimidazole (0.96 g), melting point 72°C, is obtained on recrystallization from water (4 cc). 

X-ray studies were also performed for bis(l,2,3,5-tetramethyl-4-nitropyrazolium salt [105], l-methyl-4(5)-nitro-5(4)-styrylimidazole [82], I -(/V-morpholino )-4-nitroimidazole [83], 1-sodium salt of 4-[2-[(l-methyl-5-nitro-2-imidazolyl)thio] ethoxy]-benzoic acid [106], l-methyl-4-nitro-5-chloroimidazole [107], omidazole [81], megazole [108], l-methyl-2-nitro-5-vinylimidazole [42], l-[2-(ethylsulfonyl) ethyl]-2-methyl-5-nitroimidazole (tinidazole) and one of the basic tinidazole metabolites - ammonium salt of l-[2-(ethylsulfonyl)ethyl]-4, 5-dihydro-2-methyl-4-nitroimidazole-5on [109], morpholino nitroimidazole derivatives [110, 111], l-(2-bromoethyl)-2-methyl-5-nitroimidazole [112], l-(4-chlorophenacyl)-2-methyl-... 

The dihedral angles between the imidazole ring and the attached nitro group in l-(2-chloroethyl)-2-methyl-5-nitroimidazole (chlorometronidazole) [122] and l-(2-iodoethyl)-2-methyl-5-nitroimidazole (iodometronidazole) [123] are 6.5 and 7.8°, correspondently. 

Proprietary Names. Fasigyn Simplotan. l-[2-(Ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole C8Hi3N304S = 247.3 CAS—19S87-91-8... 

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