3366-95-8

Basic information

• Product Name: alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol
• Synonyms: Secnidazole, alpha,2-DiMethyl-5-nitro-1H-iMidazole-1-ethanol;1-(2-Methyl-5-nitro-1H-iMidazol-1-yl)propan-2-ol;Secnidazole hydrate(see Data Sheet);SECNIDAZOLE;alpha,2-dimethyl-5-nitro-1h-imidazole-1-ethanol;SECNIDAZOLE, MM(CRM STANDARD);1-(2-Methyl-5-nitroimidazol-1-yl)-2-propanol;a,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol
• CAS NO: 3366-95-8
• Molecular Formula: C₇H₁₁N₃O₃
• Molecular Weight: 185.18
• EINECS: 222-134-0
• Product Categories: API;secnidazole;Active Pharmaceutical Ingredients;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 3366-95-8.mol
• Article Data: 5

Chemical Properties

• Melting Point: 76°C
• Boiling Point: 396.1 °C at 760 mmHg
• Flash Point: 193.4 °C
• Appearance: Crystalline solid
• Density: 1.39 g/cm³
• Vapor Pressure: 5.49E-07mmHg at 25°C
• Refractive Index: 1.597
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Sparingly), Methanol (Sparingly)
• PKA: 14.50±0.20(Predicted)
• Merck: 14,8419
• CAS DataBase Reference: alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol(CAS DataBase Reference)
• NIST Chemistry Reference: alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol(3366-95-8)
• EPA Substance Registry System: alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol(3366-95-8)

Safety Data

• Hazardous Substances Data: 3366-95-8(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

Different sources of media describe the Uses of 3366-95-8 differently. You can refer to the following data:
1. Analog of Metronidazole. Antiamebic. Antiprotozoal (Trichomonas)
2. antiameobic, antitrichomonas
3. Analog of Metronidazole. Antiamebic. Antiprotozoal (Trichomonas).

Pharmaceutical Applications

A 5-nitroimidazole with properties similar to those of metronidazole. It is rapidly absorbed after oral administration and is distinguished by having the longest plasma half-life (18 h) of clinically used nitroimidazole drugs. It is used in the treatment of intestinal amebiasis, giardiasis, trichomoniasis and bacterial vaginosis.

InChI:InChI=1/C7H11N3O3/c1-5(11)4-9-6(2)8-3-7(9)10(12)13/h3,5,11H,4H2,1-2H3

Synthetic route

1-bromo-2-propanol (19686-73-8) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → secnidazole (3366-95-8)

Conditions	Yield
With potassium carbonate In acetone at 70℃; for 5h; Reagent/catalyst; Temperature;	89.1%

2-methyl-5-nitro-1H-imidazole (696-23-1) + methyloxirane (75-56-9, 16033-71-9) → secnidazole (3366-95-8)

Conditions	Yield
With 1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(dimethylamino)cyclohexyl]thiourea In ethyl acetate at 25 - 30℃; for 6h; Solvent; Temperature; Reagent/catalyst;	80.5%
With aluminum (III) chloride In ethyl acetate at 45 - 50℃; for 1.5h; Temperature;	75%

1-(2-methyl-imidazol-1-yl)-propan-2-ol (34091-34-4) → secnidazole (3366-95-8)

Conditions	Yield
With magnesium(II) perchlorate; N–nitrosaccharin In [D3]acetonitrile at 85℃; for 19h; Inert atmosphere; Sealed tube;	44%

water (7732-18-5) + secnidazole (3366-95-8) + copper(ll) bromide (7789-45-9) → [Cu(secnidazole)2Br2]*0.5H2O

Conditions	Yield
In ethanol for 4h; Reflux;	96%

copper(II) choride dihydrate + secnidazole (3366-95-8) → [Cu(secnidazole)2Cl2] (1429662-19-0)

Conditions	Yield
In ethanol for 4h; Reflux;	96%

water (7732-18-5) + cobalt(II) diacetate tetrahydrate (6147-53-1) + secnidazole (3366-95-8) → [Co2(secnidazole)6(O2C2H3)2(μ2-O2 H5C3)2]·H2O

Conditions	Yield
In ethanol for 4h; Reflux;	95%

nickel(II) acetate tetrahydrate (6018-89-9) + secnidazole (3366-95-8) → [Ni2(secnidazole)4(μ2-O2C2H3)4]

Conditions	Yield
In ethanol for 4h; Reflux;	93%

oxalyl dichloride (79-37-8) + secnidazole (3366-95-8) → bis(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl) oxalate

Conditions	Yield
Stage #1: secnidazole With pyridine In toluene at 40℃; for 0.5h; Green chemistry; Stage #2: oxalyl dichloride In toluene at 40℃; for 2.5h; Green chemistry;	91%

p-chlorphenylisocyanate (104-12-1) + secnidazole (3366-95-8) → 1-methyl-2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (4-chlorophenyl)carbamate

Conditions	Yield
With ammonium chloride; triethylamine In toluene at 110℃; for 17h; Inert atmosphere;	91%

potassium tetrachloroplatinate(II) (10025-99-7) + secnidazole (3366-95-8) → (NO2CCHNC(CH3)N(CH2CH(OH)CH3))2PtCl2 (84431-19-6)

Conditions	Yield
In water solid ligand added to aq. soln. of K2(PtCl4), stirred at 50 °C for 1 h; ppt. filtered, washed with EtOH/Et2O, Et2O, dried in vac.; elem. anal.;	90%

secnidazole (3366-95-8) → 1-(2-chloropropyl)-2-methyl-5-nitro-1H-imidazole (1393310-68-3)

Conditions	Yield
With thionyl chloride at 60℃; for 6h;	90%

p-toluenesulfonyl chloride (98-59-9) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-methylbenzenesulfonate

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 25h; Reagent/catalyst;	87%

benzenesulfonyl chloride (98-09-9) + secnidazole (3366-95-8) → 1-(5-methyl-2-nitro-1H-imidazol-1-yl)propan-2-yl benzenesulfonate

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 25h; Reagent/catalyst;	85%

secnidazole (3366-95-8) + 2-Naphthalenesulfonyl chloride (93-11-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl naphthalene-2-sulfonate

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 25h; Reagent/catalyst;	85%

C17H13ClN2O2 + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1-(4-chlorophenyl)-5-(p-tolyl)-1H-pyrazole-3- carboxylate

Conditions	Yield
Stage #1: C17H13ClN2O2 With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	85%

secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-one (31876-69-4)

Conditions	Yield
With dipyridinium dichromate In dichloromethane at 20℃; for 48h; Reagent/catalyst;	84%

1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid (477712-01-9) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: 1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	84%

cobalt(II) chloride hexahydrate + secnidazole (3366-95-8) → [Co(secnidazole)3(H2O)Cl2] (1429662-20-3)

Conditions	Yield
In ethanol for 4h; Reflux;	83%

C16H10ClIN2O2 + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1-(4-chlorophenyl)-5-(4-iodophenyl)-1H-3-carboxylate

Conditions	Yield
Stage #1: C16H10ClIN2O2 With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	82%

zinc(II) nitrate hexahydrate + water (7732-18-5) + secnidazole (3366-95-8) → [Zn(secnidazole)3(NO3)][NO3]*2H2O

Conditions	Yield
In ethanol for 4h; Reflux;	81%

C18H16N2O2 + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1,5-di-p-tolyl-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: C18H16N2O2 With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	81%

4-chlorobenzenesulfonyl chloride (98-60-2) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-chlorobenzenesulfonate

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 25h; Reagent/catalyst;	80%

methanesulfonyl chloride (124-63-0) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl methanesulfonate

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 0 - 20℃; for 25h; Reagent/catalyst;	79%

C16H11IN2O2 + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-5-(4-iodophenyl)-1-phenyl-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: C16H11IN2O2 With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	79%

5-(4-methoxy-phenyl)-1-phenyl-1H-pyrazole-3-carboxylic acid (47209-42-7) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-5-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-3- carboxylate

Conditions	Yield
Stage #1: 5-(4-methoxy-phenyl)-1-phenyl-1H-pyrazole-3-carboxylic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	78%

C17H14N2O2 + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1-phenyl-5-(m-tolyl)-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: C17H14N2O2 With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	78%

3,4-dichlorophenylisocyanate (102-36-3) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl (3,4-dichlorophenyl)carbamate

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 1.16667h;	77.2%

4-methyl-benzoyl chloride (874-60-2) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-methylbenzoate

Conditions	Yield
Stage #1: secnidazole With pyridine In toluene at 70℃; for 0.5h; Green chemistry; Stage #2: 4-methyl-benzoyl chloride In toluene at 70℃; for 4.5h; Green chemistry;	77%

1,5-diphenylpyrazole-3-carboxylic acid (13599-22-9) + secnidazole (3366-95-8) → 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl-1,-5-diphenyl-1H-pyrazole-3-carboxylate

Conditions	Yield
Stage #1: 1,5-diphenylpyrazole-3-carboxylic acid With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1,2-dichloro-ethane at 45℃; for 0.5h; Stage #2: secnidazole In 1,2-dichloro-ethane Reflux;	77%

benzaldehyde (100-52-7) + secnidazole (3366-95-8) → 1-(5-nitro-2-styryl-1H-imidazol-1-yl)propan-2-ol (1448528-37-7)

Conditions	Yield
With sodium methylate In methanol; dimethyl sulfoxide at 20℃;	76.1%

nickel(II) chloride hexahydrate + water (7732-18-5) + secnidazole (3366-95-8) → [Ni(secnidazole)2(H2O)2Cl2]*5H2O

Conditions	Yield
In ethanol for 4h; Reflux;	76%

Upstream product

• 34091-34-4 1-(2-methyl-imidazol-1-yl)-propan-2-ol 
• 696-23-1 2-methyl-5-nitro-1H-imidazole 
• 75-56-9 methyloxirane 
• 19686-73-8 1-bromo-2-propanol 

Downstream Products

• 1146349-32-7 1-[4-(4-fluorobenzenesulfonylmethyl)-2-methyl-5-nitroimidazol-1-yl]propan-2-ol 

Relevant articles and documents

NITRATION

The present invention relates to a process for preparing a nitrated compound, comprising the step of reacting a compound (A) comprising at least one substituted or unsubstituted aromatic or heteroaromatic ring, wherein said heteroaromatic ring comprises at least one heteroatom selected from the group consisting of oxygen, sulfur, phosphor, selenium and nitrogen, with a compound of formula (I) wherein Y is selected from the group consisting of hydrogen and nitro.

Synthesis method of 5-nitroimidazole drugs

The invention provides a synthesis method of 5-nitroimidazole drugs. The synthesis method comprises the steps: A) mixing 2-Methyl-5-nitroimidazole, ethyl acetate and aluminum trichloride catalyst supported on macroporous resin to obtain a mixed system; B) dropwise adding epichlorohydrin or propylene oxide to the mixed system and reacting to obtain a 5-Nitroimidazole antimicrobial drug. The aluminum trichloride catalyst supported on resin is adopted, the high catalytic activity of aluminum trichloride is retained, the post-reaction treatment process is simplified, the catalyst can be separatedonly through simple filtration, and the catalyst can be recycled for 3-5 times and activity basically remains unchanged, thus greatly reducing the three wastes of the catalyst used in the traditionalprocess and reducing the energy consumption and cost. Meanwhile, the aluminum trichloride catalyst supported on the resin is adopted and the reaction temperature does not need low temperature reaction, thus saving more energy and improving the reaction yield which can reach 75% ~ 80%.

External preparation for skin diseases containing nitroimidazole

An external preparation for skin disease which comprises a nitroimidazole derivative represented by the following formula (I): wherein R1, R3 and R4 may be the same or different and represent a hydrogen atom, a nitro group, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, or a substituted lower alkenyl group; and R2 represents a hydrogen atom, a lower alkyl group, a substituted lower alkyl group and a lower alkenyl group or a substituted lower alkenyl group, provided that any one of R1, R3 and R4 is a nitro group.