Name | 3-BROMO-5-METHYL-1H-PYRAZOLE |
Synonyms | 3-Bromo-5-methylpyrazole 3-BROMO-5-METHYL-1H-PYRAZOLE 3-Bromo-5-methyl-2H-pyrazole 1H-Pyrazole, 3-broMo-5-Methyl- |
CAS | 57097-81-1 |
EINECS | 804-261-9 |
Molecular Formula | C4H5BrN2 |
Molar Mass | 161 |
Density | 1.723 |
Melting Point | 138-139 °C |
Boling Point | 270℃ |
Flash Point | 117℃ |
pKa | 11.44±0.10(Predicted) |
Storage Condition | under inert gas (nitrogen or Argon) at 2-8°C |
Use | Uses 3-bromo-5-methylpyrazole is used to prepare cyclobutanediol. |
Downstream Products | 5-Bromo-1,3-dimethyl-1H-pyrazole |
Introduction
3-Bromo-5-methyl-1H-pyrazole is an important heterocyclic compound, which exists in a variety of bioactive compounds and is used to synthesize further functionalized starting materials. 3-Bromo-5-methyl-1H-pyrazole is a key intermediate in the synthesis of a new type of fish nitine receptor insecticide chloramamide. In addition, pyrazole derivatives are symptomatic of the inhibition of adenine nucleoside triphosphate (ATP) sensitivity potassium channels in the heart muscles, such as: the treatment of cardiovascular system diseases, the treatment of arrhythmia or The treatment of cardiac contractility decline, the treatment of coronary heart disease, cardiac insufficiency or cardiomyopathy, etc., is especially suitable for the prevention of sudden cardiac death.
Preparation
1. Synthesis of 3-hydroxy-1H-pyrazol-5-ethyl acetate
Dissolve diethyl butynediate in diethyl ether, cool to -10 ℃, add 40% hydrazine hydrate solution dropwise, the system reacts exothermically, keep the temperature lower than 0 ℃, cool down to -5 ℃ after dropping, react for 30 minutes, a large amount of white solids are precipitated, white solids are filtered out, the filter residue is washed with a small amount of ether solution, the filter residue is quickly spin dried at low pressure to obtain an intermediate, and the above intermediate is placed in a single-port reaction bottle, put it into a preheated oil bath pan and raise the temperature to 100 ℃, react for 30 minutes, and there is gas coming out. TLC detects the reaction progress. After the reaction of the crude drug is finished, vacuum spin dry to obtain the product 3-hydroxy-1H-pyrazole -5-ethyl acetate.
2. Synthesis of 3-bromo-1H-pyrazol-5-ethyl acetate
Dissolve 3-hydroxy-1H-pyrazol-5-ethyl acetate in acetonitrile, add phosphorus oxybromide, raise the temperature and reflux for 15 hours, and detect the reaction progress by thin layer chromatography. After the reaction of the API is over, The reaction liquid is cooled to room temperature, slowly poured into the pre-cooled saturated sodium carbonate aqueous solution, filtered, the filtrate is extracted with ethyl acetate, extracted multiple times, combined with organic layers, and the organic layer is dried by anhydrous sodium sulfate, the organic phase is concentrated under reduced pressure to obtain a colorless to yellowish oil. After being placed in the refrigerator, a solid 3-bromo-1H-pyrazol-5-ethyl acetate is obtained.
3. Synthesis of 3-bromo-1H-pyrazol-5-acetic acid
Add ethanol to the single-port reaction bottle, dissolve 3-bromo-1H-pyrazole -5-ethyl acetate in ethanol, add 10% sodium hydroxide aqueous solution, stir for 2 hours at room temperature, and detect the reaction progress by thin layer chromatography. After the reaction of the API is over, the ethanol solution is concentrated under reduced pressure, the aqueous concentrate is added to ethyl acetate for extraction, multiple extraction, and the organic layer is combined. The pH value of the aqueous phase is adjusted to 9 with dilute hydrochloric acid, ethyl acetate was added for extraction, multiple extraction, organic layers were combined, anhydrous sodium sulfate in the organic layer was dried, and the organic phase was concentrated under reduced pressure to obtain a white solid, namely 3-bromo-1H-pyrazol-5-acetic acid.
4. Synthesis of 3-Bromo-5-methyl-1H-pyrazole
The above products were decarboxylated to prepare 3-bromo-5-methyl-1H-pyrazole. Decarboxylation reaction can occur when 3-bromo-1H-pyrazol-5-acetic acid is heated with solid NaOH. Decarboxylation reaction conditions include heating, alkaline conditions, heating and alkaline conditions coexist. Decarboxylation reaction is a reaction in which carboxylic acid loses its carboxyl group and emits carbon dioxide.
Introduction | 3-bromo-5-methyl-1h-pyrazole, an important heterocyclic compound, present in a variety of biologically active compounds for the synthesis of further functionalized starting materials. 3-bromo-5-methyl-1h-pyrazole is a key intermediate for the synthesis of a new type of chlorothionidine acceptor insecticide chlorinamide. In addition to this, pyrazole derivatives are symptomatic for the inhibition of adenine nucleoside triphosphate (ATP)-sensitive potassium channels in the heart muscle, for example: treatment of diseases of the cardiovascular system, the treatment of arrhythmia or decreased heart contractility, the treatment of coronary heart disease, cardiac insufficiency or cardiomyopathy and other diseases, especially for the prevention of sudden cardiac death. |
Use | 3-bromo-5-methylpyrazole is used for the preparation of cyclobutanediol. |
preparation | 1. Synthesis of 3-hydroxy-1h-pyrazole-5-acetic acid ethyl ester diethyl butynediate was dissolved in diethyl ether, cooled to -10 ℃, 40% hydrazine hydrate solution was added dropwise, and the reaction was exothermic, keep the temperature below 0 ℃, drop after the completion of cooling to -5 ℃ reaction for 30 minutes, a large number of white solid precipitation, Suction filtration of white solid, filter residue with a small amount of ether solution, the filter residue was quickly spin-dried under low pressure to obtain an intermediate. The intermediate was placed in a single-port reaction flask, put in a preheated oil bath and warmed to 100 ℃ for 30 minutes, after the end of the reaction of the raw material, the product 3-hydroxy-1h-pyrazole-5-ethyl acetate was obtained by vacuum drying. 2. Synthesis of 3-bromo-1h-pyrazole-5-acetic acid ethyl ester 3-hydroxy-1h-pyrazole-5-acetic acid ethyl ester was dissolved in acetonitrile, phosphorus tribromo was added, and the mixture was heated and refluxed for 15 hours, the reaction progress was checked by thin layer chromatography. After the reaction of the crude drug was completed, the reaction solution was cooled to room temperature, poured slowly into the previously cooled saturated sodium carbonate aqueous solution, filtered, and the filtrate was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and the organic phase was concentrated under reduced pressure to give a colorless to yellowish oily substance. The solid 3-bromo-1h-pyrazole-5-ethyl acetate was obtained after the refrigerator was placed. 3. Synthesis of 3-bromo-1h-pyrazole-5-acetic acid ethanol was added to a single-port reaction flask, and 3-bromo-1h-pyrazole-5-ethyl acetate was dissolved in ethanol, add 10% sodium hydroxide aqueous solution, stir at room temperature for 2 hours, check the reaction progress by thin layer chromatography, after the end of the raw material reaction, concentrate ethanol solution under reduced pressure, water concentrate is added to ethyl acetate extraction, multiple Extraction, combined organic layer, aqueous phase with dilute hydrochloric acid to adjust the pH value of 9, add ethyl acetate extraction, multiple extraction, combined organic layer, organic layer anhydrous sodium sulfate dry, organic phase decompression concentrated white solid, that is, 3-bromo-1h-pyrazole-5-acetic acid. 4. Synthesis of 3-bromo-5-methyl-1h-pyrazole the above product was subjected to decarboxylation reaction to prepare 3-bromo-5-methyl-1h-pyrazole. The decarboxylation reaction of 3-bromo-1h-pyrazole-5-acetic acid can occur under the condition of heating with solid NaOH. The decarboxylation reaction conditions include heating, alkaline conditions, and the coexistence of heating and alkaline conditions. Decarboxylation is a reaction in which a carboxylic acid loses its carboxyl group and emits carbon dioxide. |