工地图纸字母代表什么:甲硝唑 [CAS:443-48-1]合成路线图解??有机化学网

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Chemical Name： 2-Methyl-5-nitro-1H-imidazole-1-ethanol Generic Name： 甲硝唑;Metronidazole Other Names： Metronidazole;IDR-90105(Ophthalmic);Rosased;Zidoval;Metrogel;Flagyl CAS： 443-48-1 Related CAS： 133884-00-1 (deleted CAS) Formula： C₆H₉N₃O₃ Mole Weight： 171.15693 structure： Company： Pfizer (Originator), 3M Pharmaceuticals (Not Determined), Novartis (Not Determined), Pierre Fabre (Not Determined), Institute for Drug Research (Licensee) Usage： Acne Therapy, Antiamebics, Antibacterial Drugs, Antibacterial Ophthalmic Drugs, Antifungal Agents, ANTIINFECTIVE THERAPY, Antitrichomonals, DERMATOLOGIC DRUGS, Ocular Antiinflammatory and Antiinfective Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, Treatment of Protozoal Diseases Route 1 2-Methylimidazole (I) is converted into the bisulfate salt, and then nitrated by means of a sulfonitric mixture in Ac2O to produce 2-methyl-4-nitroimidazole (II) . In a variant of this procedure, 2-methylimidazole (I) is nitrated by using a ferric nitrate-tonsyl adduct in several solvents. Imidazole (II) is then regioselectively alkylated with boiling 2-chloroethanol to produce the title compound. Alternatively, the alkylation of (II) has been reported by treatment with ethylene oxide (III) under acidic conditions. Intermediates: Serial No. 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine (III) (3aR,6aS)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carbaldehyde (I) ethyl (1R,2S,4R)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate (II) Reference 1:     Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 . Reference 2:     Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 .
Route 2 In an alternative procedure, the title compound is obtained by hydrolysis of the bromoethyl imidazole (I) in the presence of formic acid in aqueous formamide Intermediates: Serial No. Reference 1:     Sunjic, V.; Fajdiga, T.; Kajfez, F.; Process for preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole. DE 1695321; GB 1138805; US 3520900 .
Route 3 The title compound can be obtained by reaction of 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (I) with ethylene oxide (II) in the presence of sulfur trioxide, followed by hydrolysis in aqueous H2SO4 Intermediates: Serial No. 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine (II) Reference 1:     Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA); Process for preparing hydroxyalkyl-1 nitro-5 imidazoles. WO 9113877 .
Route 4 In a related procedure, 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (I) is condensed with ethyleneglycol diacetate (II) in the presence of anhydrous H2SO4, followed by hydrolysis or alcoholysis under acidic conditions to produce the title compound Intermediates: Serial No. Reference 1:     Buforn, A.; Massonneau, V.; Mulhauser, M. (Aventis SA); Process for the preparation of 1-hydroxyalkyl-2-methyl-5-nitro-imidazoles. EP 0325513; FR 2625999 .
Route 5 Alternatively, 2-methyl-4-nitroimidazole (I) is protected by acylation in hot acetic anhydride to give (II). Addition of ethylene oxide (III) to the N-acetyl imidazole (II) in the presence of SO3, followed by acidic hydrolysis furnishes the title compound Intermediates: Serial No. 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine (III) ethyl (1R,2S,4R)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate (I) Reference 1:     Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA); Process for preparing hydroxyalkyl-1 nitro-5 imidazoles. WO 9113877 .
Route 6 The title compound can also be obtained by alkylation, in different solvents, of 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (I) with either ethylene sulfate (II) or with bis-(2-acetoxyethyl) sulfate (III) -generated from ethyleneglycol diacetate (IV) and either dimethyl sulfate or H2SO4 - followed by hydrolysis or alcoholysis treatment Intermediates: Serial No. Reference 1:     Massonneau, V.; Mulhauser, M.; Buforn, A. (Aventis Pharma SA); Process for the preparation of hydroxyalkylating agents, the agents so prepared and their use. EP 0324692 . Reference 2:     Massonneau, V.; Mulhauser, M.; Buforn, A.; Madard-Cazin, B. (Aventis Pharma SA); Process for the preparation of 1-hydroxyalkyl-5-nitro-imidazoles. EP 0324691 .