2-Nitroimidazole Usage and Synthesis |
Background |
Malignant tumors are common diseases that seriously threaten human life. About 70% to 80% of tumor patients need to receive radiotherapy.
Radiosensitizers have attracted widespread attention in radiotherapy because they can increase the sensitivity of tumor cells to radiation.
2-Nitroimidazole is an important intermediate of many tumor radiotherapy sensitizers, such as misonidazole, pimonidazole, etanidazole, etc.
2-Nitroimidazole cannot be prepared by direct nitration of imidazole. Direct nitration of imidazole will produce 4(5)-nitroimidazole, but not 2-nitroimidazole. |
Application |
2-Nitroimidazole is the basic raw material for the synthesis of nitroimidazole compounds in the manufacture of electrophilic radiosensitizers.
N-substituted derivatives prepared from 2-nitroimidazole have begun to be used as anti-tumor radiosensitizers in clinical research.
2-Nitroimidazole is an important intermediate of many tumor radiotherapy sensitizers, such as misonidazole, pimonidazole, etanidazole, etc. |
Preparation |
Add 305g of imidazole-type ionic liquid to a clean and dry 1000ml reactor, slowly add 304g of bromine under stirring at 20℃,
the reaction is exothermic, control the temperature at 20-30℃, add dropwise, and complete the addition in about 0.5h to obtain a reddish-brown liquid.
Add 136g of imidazole in 5 batches, keep warm and stir at 20-30℃ for 2.0h, and extract the hydrogen bromide gas generated by the reaction with a slight negative pressure,
and absorb the discharged hydrogen bromide gas with clean water. Liquid chromatography detection shows that the raw material point reaction is complete,
the reactant is extracted with toluene three times, 400ml of toluene is added each time, and the toluene extract is concentrated under reduced pressure to obtain 216.
3g of 2-bromoimidazole product. Add 189g of dimethyl sulfoxide, 100g of 2-bromoimidazole, 1g of cuprous iodide, and 93.8g of sodium nitrite to a clean and dry 500L reactor.
Slowly heat to 120℃ in an oil bath and keep warm for 8h. After the insulation, cool to 50℃, add 200g of water, and extract with ethyl acetate three times.
After concentrating the ethyl acetate, the crude product is recrystallized with ethanol to obtain 52.3g of 2-nitroimidazole, with a yield of 68.1%,
a content of more than 98.5%, and a melting point of 286-288℃. |
Chemical properties |
Pale yellow crystals. Melting point 283℃ (decomposition). Soluble in methanol, ethanol, acetone, and ethyl acetate, insoluble in ether and chloroform. |
Uses |
Intermediate of tumor radiotherapy sensitizer misonidazole (Misonidazole). |
Uses |
The intermediate of tumor radiotherapy sensitizer misonidazole is used as an organic synthesis intermediate |
Use |
It is used to prepare nitroimidazole-substituted boric acid, which can be used as a precursor for hypoxic tissue imaging.
It is also used to prepare available site-selective radiosensitizers for tumors rich in estrogen receptors. |
Production method |
Mix aminoacetal S-methylisothioate and water, stir and heat, evaporate to dryness under reduced pressure, add methanol to dissolve the residue,
and then add acetone dropwise to obtain white crystalline N-(2,2-diethoxyethyl)guanidine sulfate with a yield of 84.4%.
Take N-(2,2-diethoxyethyl)guanidine sulfate and concentrated hydrochloric acid, mix them, stir and heat to reflux, after the reaction,
add distilled water and evaporate to dryness under reduced pressure, then add water and evaporate to dryness, dissolve the residue with anhydrous ethanol,
and then add anhydrous ether dropwise to obtain white solid 2-aminoimidazole with a yield of 64.5%. 2-aminoimidazole, add fluoroboric acid and water,
cool to below -15°C, and add a solution of sodium nitrate and water dropwise while stirring. After the addition, continue stirring.
Pour the brown-green solution generated by the reaction into a copper sulfate pentahydrate solution, add while stirring, then add sodium nitrite and continue stirring.
After the reaction is completed, add concentrated hydrochloric acid to adjust the pH to 2, extract with acetate, dry the extract with anhydrous sodium sulfate,
and recover ethyl acetate until it is exhausted. The residue is recrystallized with ethanol to obtain 2-nitroimidazole. |
