696-23-1

Basic information

• Product Name: 2-Methyl-4-nitroimidazole
• Synonyms: 2-METHYL-4-NITRO-1 H-IMIDAZOLE;2-METHYL-4(5)-NITROIMIDAZOLE;2-methyl-4-nitro-1h-imidazol;2-methyl-4-nitro-imidazol;2-methyl-4-nitroimidazole;2-Methyl-5-nitro-1H-imidazole (9CI);Imidazole, 2-methyl-4-nitro-;Imidazole, 2-methyl-5-nitro-
• CAS NO: 696-23-1
• Molecular Formula: C₄H₅N₃O₂
• Molecular Weight: 127.1
• EINECS: 211-790-3
• Product Categories: Imidaxoles;Building Blocks;Heterocyclic Building Blocks;Imidazoles;Heterocycles;Metabolites & Impurities;Heterocycles, Metabolites & Impurities
• Mol File: 696-23-1.mol
• Article Data: 19

Chemical Properties

• Melting Point: 251-255 °C(lit.)
• Boiling Point: 235.85°C (rough estimate)
• Flash Point: 195℃
• Appearance: solid
• Density: 1.4748 (rough estimate)
• Vapor Pressure: 3.14E-06mmHg at 25°C
• Refractive Index: 1.5000 (estimate)
• Storage Temp.: Refrigerator
• PKA: 8.87±0.10(Predicted)
• Water Solubility: 3.01g/L(20 oC)
• Stability: Stable. Incompatible with strong oxidizing agents.
• BRN: 4032
• CAS DataBase Reference: 2-Methyl-4-nitroimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methyl-4-nitroimidazole(696-23-1)
• EPA Substance Registry System: 2-Methyl-4-nitroimidazole(696-23-1)

Safety Data

• Hazard Codes: Xn
• Statements: 68-40-22
• Safety Statements: 36/37
• WGK Germany: 3
• RTECS: NI7550000
• TSCA: Yes
• Hazardous Substances Data: 696-23-1(Hazardous Substances Data)

Usage

Chemical Properties

solid

Uses

Different sources of media describe the Uses of 696-23-1 differently. You can refer to the following data:
1. Floconazole impurity.
2. 2-Methyl-4(5)-nitroimidazole was used to study the mechanism of both the alkaline and acidic hydrolysis of tinidazole.

General Description

Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

InChI:InChI=1/C4H5N3O2/c1-3-5-2-4(6-3)7(8)9/h2H,1H3,(H,5,6)

Synthetic route

2-methylimidazole (693-98-1) → 2-methyl-5-nitro-1H-imidazole (696-23-1)

Conditions	Yield
With sulfuric acid; nitric acid; sodium sulfate at 80℃; for 0.0363889h; Temperature; Microwave irradiation;	90.5%
With sulfuric acid; nitric acid In diethyl ether at 0 - 140℃;	39%
With sulfuric acid; nitric acid
With sulfuric acid; nitric acid; sodium sulfate In water at 130 - 132℃; for 4h;
With sulfuric acid; nitric acid; sodium sulfate at 150℃; for 2h;	3.8 g

2-methylimidazole (693-98-1) → 2-methyl-5-nitro-1H-imidazole (696-23-1) + 2-(dinitromethylene)-5,5-dinitro-4-imidazolidinone (214191-53-4) + ammonium salt of parabanic acid

Conditions	Yield
With sulfuric acid; nitric acid for 3h; Nitration;

2-methylimidazole (693-98-1) → 2-methyl-5-nitro-1H-imidazole (696-23-1) + ammonium salt of parabanic acid

Conditions	Yield
With sulfuric acid; nitric acid Nitration;	A 0.5 g B 4.5 g

1,4-Dihydro-2,6-dimethyl-4-(2-methyl-5-nitroimidazol-1-yl)methylpyridin-3,5-dicarbonsaeuredimethylester → 2-methyl-5-nitro-1H-imidazole (696-23-1) + dimethyl 2,6-dimethylpyridine-3,5-dicarboxylate (27525-74-2)

Conditions	Yield
With ammonium cerium(IV) nitrate Product distribution; Decomposition;

2-methylimidazole (693-98-1) → 2-methyl-5-nitro-1H-imidazole (696-23-1) + 2-methyl-4-nitro-1H-imidazole (696-23-1)

Conditions	Yield
With sulfuric acid; nitric acid In water at 130 - 132℃; for 4h;

metronidazole (443-48-1) → 2-methyl-5-nitro-1H-imidazole (696-23-1) + 2-(5-amino-2-methyl-1H-imidazol-1-yl)ethan-1-ol (84145-87-9) + N-(2'-hydroxyethyl)-2-methylimidazole (1615-15-2)

Conditions	Yield
With sodium tetrahydroborate; iron at 25℃; pH=7;

4-iodo-2-methyl-5-nitro-1H-imidazole (13369-83-0) → 2-methyl-5-nitro-1H-imidazole (696-23-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 25℃; under 50 Torr; for 0.333333h; Pressure;	89 %Chromat.

4-bromo-2-methyl-5-nitroimidazole (18874-52-7) → 2-methyl-5-nitro-1H-imidazole (696-23-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 25℃; under 100 Torr; for 0.5h; Pressure;	47 %Chromat.

2-(5-bromopentyl)-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 2-(2,4-dichlorophenyl)-5-(5-(2-methyl-5-nitro-1H-imidazol-1-yl)pentyl)-1,3,4-oxadiazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h;	99.9%

2-methyl-5-nitro-1H-imidazole (696-23-1) + methanesulfonic acid 7-[tert-butoxycarbonyl-(2-tert-butoxycarbonylamino-ethyl)-amino]-6-{[tert-butoxycarbonyl-(2-tert-butoxycarbonylamino-ethyl)-amino]-methyl}-heptyl ester (663612-70-2) → (2-tert-butoxycarbonylamino-ethyl)-[2-{[tert-butoxycarbonyl-(2-tert-butoxycarbonylamino-ethyl)-amino]-methyl}-7-(2-methyl-4-nitro-imidazol-1-yl)-heptyl]-carbamic acid tert-butyl ester (663612-73-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	98%

bromoacetic acid tert-butyl ester (5292-43-3) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → tert-butyl 2-(2-methyl-5-nitroimidazol-1-yl)acetate

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 50℃; for 0.5h; Stage #2: bromoacetic acid tert-butyl ester In acetonitrile Reflux;	95.6%
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 50℃; for 0.5h; Stage #2: bromoacetic acid tert-butyl ester In acetonitrile Reflux;

2-methyl-5-nitro-1H-imidazole (696-23-1) + acrylic acid methyl ester (292638-85-8) → methyl 3-(2-methyl-5-nitro-1H-imidazol-1-yl)propanoate (1273542-72-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 168h; Michael Addition; Inert atmosphere;	95.6%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 168h; Inert atmosphere;	95.6%

2-methyl-5-nitro-1H-imidazole (696-23-1) + dimethyl sulfoxide (67-68-5) → 2-methyl-1-methylthiomethyl-5-nitroimidazole

Conditions	Yield
for 50h; Heating;	95%

vinyl acetate (108-05-4) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 1-(2-methyl-4-nitro-1H-imidazol-1-yl)ethyl acetate

Conditions	Yield
With potassium phosphate In N,N-dimethyl-formamide at 20℃; for 10h; aza-Markovnikov addition;	95%

2-phenyl-3-((3-bromopropoxy)methyl)-imidazo[2,1-b] benzothiazole + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 2-phenyl-3-((3-(2-methyl-5-nitro-1H-imidazol-1-yl)propoxy) methyl)-imidazo[2,1-b]benzothiazole

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile Heating; Stage #2: 2-phenyl-3-((3-bromopropoxy)methyl)-imidazo[2,1-b] benzothiazole In acetonitrile Heating;	94.6%

2-phenyl-3-((3-bromopropoxy)methyl)-imidazo[2,1-b] benzothiazole + 2-methyl-5-nitro-1H-imidazole (696-23-1) → C23H21N5O3S

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: 2-phenyl-3-((3-bromopropoxy)methyl)-imidazo[2,1-b] benzothiazole In acetonitrile at 60℃;	94.2%

vinyl n-butyrate (123-20-6) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 1-(2-methyl-4-nitro-1H-imidazol-1-yl)ethyl butyrate

Conditions	Yield
With potassium phosphate In N,N-dimethyl-formamide at 20℃; for 30h; aza-Markovnikov addition;	94%

3-chloropropiophenone (936-59-4) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 3-(2-methyl-5-nitro-1H-imidazol-1-yl)-1-phenylpropan-1-one (38938-81-7)

Conditions	Yield
With triethylamine In toluene at 20℃; Reflux;	94%

vinyl benzoate (769-78-8) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 1-(2-methyl-4-nitro-1H-imidazol-1-yl)ethyl benzoate

Conditions	Yield
With potassium phosphate In N,N-dimethyl-formamide at 50℃; for 30h; aza-Markovnikov addition;	93%

2-methyl-5-nitro-1H-imidazole (696-23-1) → 4-bromo-2-methyl-5-nitroimidazole (18874-52-7)

Conditions	Yield
With bromine; sodium carbonate In N,N-dimethyl-formamide at 70℃; for 2h;	93%
With bromine In N,N-dimethyl-formamide at 40℃; for 4h; Cooling with ice;	75%

2-methyl-5-nitro-1H-imidazole (696-23-1) + 1-phenyl-2-bromoethane (103-63-9) → 2-methyl-4-nitro-1-phenethyl-1H-imidazole (195046-60-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 8h; Schlenk technique; Inert atmosphere;	93%

C21H21BrN2O2S + 2-methyl-5-nitro-1H-imidazole (696-23-1) → C25H25N5O4S

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: C21H21BrN2O2S In acetonitrile at 60℃;	93%

2-methyl-5-nitro-1H-imidazole (696-23-1) + methanesulfonic acid 6,6-bis-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-hexyl ester (327065-15-6) → {2-[2-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-7-(2-methyl-4-nitro-imidazol-1-yl)-heptanoylamino]-ethyl}-carbamic acid tert-butyl ester (327065-17-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	92%

C21H21BrN2OS + 2-methyl-5-nitro-1H-imidazole (696-23-1) → C25H25N5O3S

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: C21H21BrN2OS In acetonitrile at 60℃;	92%

C23H25BrN2O2S + 2-methyl-5-nitro-1H-imidazole (696-23-1) → C27H29N5O4S

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: C23H25BrN2O2S In acetonitrile at 60℃;	91%

2-methyl-5-nitro-1H-imidazole (696-23-1) + acrylonitrile (107-13-1) → 3-(2-methyl-4-nitro-1H-imidazol-1-yl)propanenitrile (14885-27-9)

Conditions	Yield
With potassium carbonate Reflux;	90%
With polystyrene-supported CuI-imidazole complex catalyst In N,N-dimethyl-formamide at 100℃; for 10h; Aza-Michael reaction;	77%

1,4-dibromo-butane (110-52-1) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 2-methyl-3-(4-(2-methyl-5-nitro-1H-imidazoliumbromide)butyl)-5-nitro-1H-imidazolium bromide

Conditions	Yield
With silica gel In neat (no solvent) at 100℃; for 4.5h;	90%

ethyl 1-(oxiran-2-ylmethyl)-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate (1435910-86-3) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → ethyl 1-(2-hydroxy-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propyl)-4-oxo-6-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate

Conditions	Yield
With potassium carbonate In ethanol at 60℃; for 1.5h;	89.3%

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) + propargyl bromide (106-96-7) → N1-propargyl-2-methyl-4-nitroimidazole (153563-43-0) + 2‐methyl‐5‐nitro‐1‐prop‐2‐ynyl‐1H‐imidazole (22927-54-4)

Conditions	Yield
With potassium carbonate In acetone; toluene at 20℃; Inert atmosphere;	A n/a B 89%

2-methyl-5-nitro-1H-imidazole (696-23-1) + phenoxyethyl bromide (589-10-6) → 2-methyl-4-nitro-1-(2-phenoxyethyl)-1H-imidazole (16183-76-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 8h; Schlenk technique; Inert atmosphere;	89%

ethyl 6-methyl-1-(oxiran-2-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (1435910-84-1) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → ethyl 1-(2-hydroxy-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propyl)-6-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate

Conditions	Yield
With potassium carbonate In ethanol at 60℃; for 1.5h;	88.4%

(S)-epichlorohydrin (67843-74-7) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → (S)-(-)-1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (16773-42-5)

Conditions	Yield
With aluminum (III) chloride In ethyl acetate at 3 - 5℃;	88.2%
With formic acid; sulfuric acid at 30 - 40℃; for 4.5h; Reagent/catalyst; Temperature;	83.9%
With formic acid; sulfuric acid at -5 - 15℃; for 2h; Reagent/catalyst;	403 g
With boron trifluoride In ethyl acetate at -10 - 15℃; for 5h; Darkness; Large scale;	3.21 kg
With boron trifluoride In ethyl acetate at -10 - 15℃; for 5h; Darkness; Large scale;	3.21 kg

oxirane (75-21-8) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → metronidazole (443-48-1)

Conditions	Yield
With formic acid; sulfuric acid at 80℃; for 12h; Temperature;	88%
With formic acid at 50 - 60℃; for 0.5h; Reagent/catalyst; Temperature;	74.9%
With phosphoric acid; acetic anhydride In water at 25 - 30℃; for 2.5h; Yield given;
With sulfuric acid; acetic acid at 90℃; for 0.5h; Concentration; Temperature; Cooling;
With formic acid; sulfuric acid Large scale;

1-bromo-butane (109-65-9) + 2-methyl-5-nitro-1H-imidazole (696-23-1) → 1-butyl-2-methyl-4-nitro-1H-imidazole (135009-57-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 8h; Schlenk technique; Inert atmosphere;	88%

2-methyl-5-nitro-1H-imidazole (696-23-1) + dimethyl sulfate (77-78-1) → dimetridazole (551-92-8)

Conditions	Yield
With formic acid for 4h; Reflux;	87%

C26H31BrN2OS + 2-methyl-5-nitro-1H-imidazole (696-23-1) → C30H35N5O3S

Conditions	Yield
Stage #1: 2-methyl-5-nitro-1H-imidazole With potassium carbonate In acetonitrile at 60℃; for 1h; Stage #2: C26H31BrN2OS In acetonitrile at 60℃;	87%

Upstream product

• 693-98-1 2-methylimidazole 
• 443-48-1 metronidazole 
• 18874-52-7 4-bromo-2-methyl-5-nitroimidazole 
• 13369-83-0 4-iodo-2-methyl-5-nitro-1H-imidazole 
• 19182-82-2 2-methyl-1,4-dinitro-1H-imidazole 

Downstream Products

• 13230-04-1 1,2-dimethyl-4-nitro-1H-imidazole 
• 551-92-8 dimetridazole 
• 56-40-6 glycine 
• 107108-25-8 2-Methyl-4-nitro-1-(4-nitrophenylmethyl)-1H-imidazole 
• 126664-28-6 4-<2-methyl-4-nitro-1-imidazolyl>-2-butanone 
• 13230-22-3 2-Methyl-4-nitroimidazole-1-acetic acid ethyl ester 
• 89128-08-5 3-(2-methyl-4-nitro-imidazol-1-yl)propionitrile 
• 7664-41-7 ammonia 
• 143-37-3 acetamidine 
• 58216-76-5 4-Acetamido-1-acetyl-2-methylimidazole 
• 4442-41-5 diphenoxymethane 
• 1359033-88-7 4'-O-demethyl-4β-(2-methyl-5-nitro-1H-imidazol-1-yl)-4-desoxypodophyllotoxin 
• 1359033-86-5 4β-(2-methyl-5-nitro-1H-imidazol-1-yl)-4-desoxypodophyllotoxin 
• 13182-81-5 1-(2-chloroethyl)-2-methyl-5-nitro-1H-imidazole 

Relevant articles and documents

Process for synthesizing 2 - methyl -5 nitroimidazole

The invention discloses a synthesis process of 2 - methyl -5 nitroimidazole, which comprises the following steps: (1) a synthesis reaction. (2) In neutralization, centrifugation. (3) A dry package. The step (2) further comprises a sodium nitrite recovery process. The waste water is added into a multi-effect evaporation crystallizer for concentration mother liquor, sodium nitrate is crystallized out, sodium nitrate crystals are separated through a horizontal spiral centrifugal machine, and then the sodium nitrate finished product is obtained through an airflow dryer. The process is more suitable for large-scale production, the consumption of main materials is greatly reduced, concentrated sulfuric acid is not added, the production cost is lower, and the sodium nitrate - hydrochloric acid mixed system used in the invention is more favorable for removing excess nitric acid and hydrochloric acid in the reaction liquid. The product yield reaches 97.0% or more, and the product content reaches 99.8% or more.

Continuous synthesis method for 2-methyl-5-nitroimidazole

The invention provides a continuous synthesis method for 2-methyl-5-nitroimidazole. The 2-methyl-5-nitroimidazole is synthesized in a micro-channel reactor. The synthesis method provided by the invention can realize continuous synthesis, is safe and stable in production process, extremely short in reaction time and high in yield, and can reduce the usage amount of concentrated sulfuric acid and lower cost.

Nitro-imidazoles in ferrocenyl alkylation reaction. Synthesis, enantiomeric resolution and in vitro and in vivo bioeffects

Ferrocenylalkyl nitro-imidazoles (4a-h, 5a-h) were prepared via the regiospecific reaction of the α-(hydroxy)alkyl ferrocenes, FcCHR (OH) (1a–h; Fc = ferrocenyl; R = H, Me, Et, Pr, i-Pr, Ph, ortho-Cl-Ph, ortho-I-Ph), with nitro-imidazoles in aqueous organic medium (H2O-CH2Cl2) at room temperature in the presence of HBF4, within several minutes in good yields. X-ray structural data for racemic (R,S)-1-N-(benzyl ferrocenyl)-2-methyl-4-nitroimidazole (5f) were determined. The resulting enantiomers were resolved into enantiomers by analytical HPLC on modified amylose or cellulose chiral stationary phases. The viabilities of 4b, 4d, 5b, 5c in vitro, and in experiments in vivo antitumor effects of 1-N-ferrocenylethyl-4-nitroimidazole (4b) against murine solid tumor system Ca755 carcinoma were evaluated.