阅读说明：本技术 一种3-溴-1-（3-氯-2-吡啶基）-1h-吡唑-5-羧酸的制备方法 (Preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid ) 是由 蒋信义 刘汝章 徐军 张敏华 于 2019-09-05 设计创作，主要内容包括：本发明涉及羧酸制备应用技术领域,且公开了一种3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的制备方法,包括以下步骤：1)、2)、3)、4)和5)。该3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的制备方法,通过步骤1)选用2,3-二氯吡啶为起始原料并与水合肼混合,然后通过一系列制取得到白色针状晶体,且步骤2)的制取中得到土黄色固体,并且在步骤3)时加入二氯乙烷、苯磺酰氯、饱和碳酸氢钠溶液并进行制取得到得暗红色油状物,最终在反应容器中加入烃基和羧基进行混合搅拌,后加入乙腈和浓硫酸并进行二次搅拌和反应,进而完成制备,整体流程十分便捷,从而有效的解决了现有技术较少可以便捷制备羧酸的问题。(The invention relates to the technical field of carboxylic acid preparation and application, and discloses a preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, which comprises the following steps: 1) 2), 3), 4) and 5). The preparation method of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid comprises the steps of 1) selecting 2, 3-dichloropyridine as a starting raw material and mixing with hydrazine hydrate, then obtaining white needle crystals through a series of preparation, obtaining an earthy yellow solid in the step 2) preparation, adding dichloroethane, benzenesulfonyl chloride and a saturated sodium bicarbonate solution in the step 3) to prepare a dark red oily substance, finally adding a hydrocarbon group and a carboxyl group into a reaction container to mix and stir, then adding acetonitrile and concentrated sulfuric acid to perform secondary stirring and reaction, and further completing preparation.)

1. A method for preparing 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, comprising the steps of:

1) carrying out primary preparation: preparing a reaction container, firstly, selecting 2, 3-dichloropyridine as a starting raw material, mixing the 2, 3-dichloropyridine with hydrazine hydrate to prepare 3-chloro-2-hydrazinopyridine, then adding ethanol and hydrazine hydrate into the reaction container, wherein the ratio of the ethanol to the hydrazine hydrate is 1:4, dripping ethanol solution under reflux to mix the ethanol solution and the hydrazine hydrate, heating at the moment, wherein the heating temperature is 150-160 ℃, the reflux time is 60-80 minutes, the reflux reaction time is 24-26 hours, carrying out ice bath cooling, separating out a large amount of solids after the ice bath cooling, and drying a filter cake to obtain white needle crystals;

2) obtaining white needle crystals after the preparation of the step 1), adding anhydrous ethanol into a reaction container, wherein the content of the anhydrous ethanol is 50-60mL, and the content of the anhydrous ethanol is 20g of metal sodium, heating and refluxing till sodium blocks are completely dissolved, cooling to room temperature, stirring, heating to reflux after the reaction liquid is yellow emulsion, carrying out reflux reaction for 60-80 minutes, cooling to 65 ℃, adjusting to H5 with glacial acetic acid, carrying out ice bath cooling, crystallizing, carrying out suction filtration, and drying a filter cake to obtain an earthy yellow solid;

3) obtaining a yellowish-earthy solid after the preparation of the step 2), adding dichloroethane and benzenesulfonyl chloride into a reaction container, cooling to 0 ℃, stirring for 50-60 minutes, dropwise adding triethylamine during stirring, reacting at 0 ℃, reacting for 2-4 hours, returning the temperature, slowly introducing gaseous bromine hydride when the temperature is returned to 10-15 ℃, introducing the gaseous bromine hydride for 45-60 minutes, dropwise adding a saturated sodium bicarbonate solution, mixing and washing, separating an organic phase after mixing and washing until no bubbles are generated, drying with anhydrous sodium sulfate, and removing the solvent under reduced pressure to obtain a dark red oily substance;

4) obtaining a dark red oily substance after the preparation of the step 3), adding alkyl and carboxyl into a reaction container, mixing and stirring for 30 minutes, then adding acetonitrile and concentrated sulfuric acid, stirring for 15 to 20 minutes, adding potassium persulfate after stirring, refluxing for 2 hours, filtering after refluxing, concentrating the filtrate under reduced pressure to about 40mL, cooling to 0 ℃ in an ice bath, carrying out suction filtration, and drying a filter cake to obtain a yellow solid, thereby completing the preparation;

5) after the preparation is finished, a detection instrument is adopted for detection, sampling test is carried out, the sampling test is carried out according to the preparation sample range proportion of 1: 100, and the preparation process can be finished after the test structure is qualified.

Technical Field

The invention relates to the technical field of carboxylic acid preparation and application, in particular to a preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid.

Background

The organic compound formed by connecting hydrocarbyl and carboxyl is called carboxylic acid, the boiling point of saturated monocarboxylic acid is even higher than that of alcohol with similar relative molecular mass, the relative molecular mass of formic acid and ethanol is the same, but the boiling point of ethanol is 78.5 ℃, the boiling point of formic acid is 100.7 ℃, carboxyl is hydrophilic group, and can form hydrogen bond with water, so that lower carboxylic acid can be mutually dissolved with water at any ratio, and as the relative molecular mass increases, the hydrophobic group (hydrocarbyl) is larger and larger, and the solubility in water is smaller and smaller.

Carboxylic acid is a very important chemical substance, and many other common chemical substances can be derived, such as acyl halide, anhydride, ester, amide and the like, and the carboxylic acid derivatives have characteristics and have important application in chemical industry, but the prior art is less and convenient to prepare, so that the preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid has good production significance, and the preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid is provided to solve the problems.

Disclosure of Invention

Technical problem to be solved

Aiming at the defects of the prior art, the invention provides a preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, which has the advantages of convenient preparation and the like and solves the problem that the prior art is less in quantity and can be used for conveniently preparing the carboxylic acid.

(II) technical scheme

The technical problem to be solved by the invention is to provide a preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, which comprises the following steps:

1) carrying out primary preparation: preparing a reaction container, firstly, selecting 2, 3-dichloropyridine as a starting raw material, mixing the 2, 3-dichloropyridine with hydrazine hydrate to prepare 3-chloro-2-hydrazinopyridine, then adding ethanol and hydrazine hydrate into the reaction container, wherein the ratio of the ethanol to the hydrazine hydrate is 1:4, dripping ethanol solution under reflux to mix the ethanol solution and the hydrazine hydrate, heating at the moment, wherein the heating temperature is 150-160 ℃, the reflux time is 60-80 minutes, the reflux reaction time is 24-26 hours, carrying out ice bath cooling, separating out a large amount of solids after the ice bath cooling, and drying a filter cake to obtain white needle crystals;

2) obtaining white needle crystals after the preparation of the step 1), adding anhydrous ethanol into a reaction container, wherein the content of the anhydrous ethanol is 50-60mL, and the content of the anhydrous ethanol is 20g of metal sodium, heating and refluxing till sodium blocks are completely dissolved, cooling to room temperature, stirring, heating to reflux after the reaction liquid is yellow emulsion, carrying out reflux reaction for 60-80 minutes, cooling to 65 ℃, adjusting to H5 with glacial acetic acid, carrying out ice bath cooling, crystallizing, carrying out suction filtration, and drying a filter cake to obtain an earthy yellow solid;

3) obtaining a yellowish-earthy solid after the preparation of the step 2), adding dichloroethane and benzenesulfonyl chloride into a reaction container, cooling to 0 ℃, stirring for 50-60 minutes, dropwise adding triethylamine during stirring, reacting at 0 ℃, reacting for 2-4 hours, returning the temperature, slowly introducing gaseous bromine hydride when the temperature is returned to 10-15 ℃, introducing the gaseous bromine hydride for 45-60 minutes, dropwise adding a saturated sodium bicarbonate solution, mixing and washing, separating an organic phase after mixing and washing until no bubbles are generated, drying with anhydrous sodium sulfate, and removing the solvent under reduced pressure to obtain a dark red oily substance;

4) obtaining a dark red oily substance after the preparation of the step 3), adding alkyl and carboxyl into a reaction container, mixing and stirring for 30 minutes, then adding acetonitrile and concentrated sulfuric acid, stirring for 15 to 20 minutes, adding potassium persulfate after stirring, refluxing for 2 hours, filtering after refluxing, concentrating the filtrate under reduced pressure to about 40mL, cooling to 0 ℃ in an ice bath, carrying out suction filtration, and drying a filter cake to obtain a yellow solid, thereby completing the preparation;

5) after the preparation is finished, a detection instrument is adopted for detection, sampling test is carried out, the sampling test is carried out according to the preparation sample range proportion of 1: 100, and the preparation process can be finished after the test structure is qualified.

(III) advantageous effects

Compared with the prior art, the invention provides a preparation method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, which has the following beneficial effects:

1. the preparation method of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid comprises the steps of 1) selecting 2, 3-dichloropyridine as a starting raw material and mixing with hydrazine hydrate, then obtaining white needle crystals through a series of preparation, obtaining an earthy yellow solid in the step 2) preparation, adding dichloroethane, benzenesulfonyl chloride and a saturated sodium bicarbonate solution in the step 3) and preparing to obtain a dark red oily substance, finally adding a hydrocarbon group and a carboxyl group in a reaction container for mixing and stirring, then adding acetonitrile and concentrated sulfuric acid and carrying out secondary stirring and reaction, further completing the preparation, wherein the whole process is very convenient and fast, the effect of convenient preparation is achieved, and the preparation process from the step 1) to the step 4) is carried out in the reaction container all the time, and the preparation process comprises stirring, heating, cooling, reacting, filtering, suction filtering and the like, so that the preparation method is simple and safe.

2. According to the preparation method of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, a detection instrument is required to be used for detection after the preparation in the steps 1) to 4) is completed, sampling test is carried out, the sampling test is carried out according to the range proportion of the preparation sample of 1: 100, the preparation process can be completed after the test structure is qualified, the problem of poor qualification rate during the preparation by using the preparation method can be effectively avoided, the whole preparation process in the steps 1) to 4) in the preparation method is very convenient, the practicability and the popularization capability of the preparation method can be effectively enhanced, and therefore the problem that the carboxylic acid can be conveniently prepared in the prior art is effectively solved.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

1. A method for preparing 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, comprising the steps of:

1) carrying out primary preparation: preparing a reaction container, firstly, selecting 2, 3-dichloropyridine as a starting raw material, mixing the 2, 3-dichloropyridine with hydrazine hydrate to prepare 3-chloro-2-hydrazinopyridine, then adding ethanol and hydrazine hydrate into the reaction container, wherein the ratio of the ethanol to the hydrazine hydrate is 1:4, dripping ethanol solution under reflux to mix the ethanol solution and the hydrazine hydrate, heating at the moment, wherein the heating temperature is 150-160 ℃, the reflux time is 60-80 minutes, the reflux reaction time is 24-26 hours, carrying out ice bath cooling, separating out a large amount of solids after the ice bath cooling, and drying a filter cake to obtain white needle crystals;

2) obtaining white needle crystals after the preparation of the step 1), adding anhydrous ethanol into a reaction container, wherein the content of the anhydrous ethanol is 50-60mL, and the content of the anhydrous ethanol is 20g of metal sodium, heating and refluxing till sodium blocks are completely dissolved, cooling to room temperature, stirring, heating to reflux after the reaction liquid is yellow emulsion, carrying out reflux reaction for 60-80 minutes, cooling to 65 ℃, adjusting to H5 with glacial acetic acid, carrying out ice bath cooling, crystallizing, carrying out suction filtration, and drying a filter cake to obtain an earthy yellow solid;

3) obtaining a yellowish-earthy solid after the preparation of the step 2), adding dichloroethane and benzenesulfonyl chloride into a reaction container, cooling to 0 ℃, stirring for 50-60 minutes, dropwise adding triethylamine during stirring, reacting at 0 ℃, reacting for 2-4 hours, returning the temperature, slowly introducing gaseous bromine hydride when the temperature is returned to 10-15 ℃, introducing the gaseous bromine hydride for 45-60 minutes, dropwise adding a saturated sodium bicarbonate solution, mixing and washing, separating an organic phase after mixing and washing until no bubbles are generated, drying with anhydrous sodium sulfate, and removing the solvent under reduced pressure to obtain a dark red oily substance;

4) obtaining a dark red oily substance after the preparation of the step 3), adding alkyl and carboxyl into a reaction container, mixing and stirring for 30 minutes, then adding acetonitrile and concentrated sulfuric acid, stirring for 15 to 20 minutes, adding potassium persulfate after stirring, refluxing for 2 hours, filtering after refluxing, concentrating the filtrate under reduced pressure to about 40mL, cooling to 0 ℃ in an ice bath, carrying out suction filtration, and drying a filter cake to obtain a yellow solid, thereby completing the preparation;

5) after the preparation is finished, a detection instrument is adopted for detection, sampling test is carried out, the sampling test is carried out according to the preparation sample range proportion of 1: 100, and the preparation process can be finished after the test structure is qualified.

The invention has the beneficial effects that: the preparation method of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid comprises the steps of 1) selecting 2, 3-dichloropyridine as a starting raw material and mixing with hydrazine hydrate, then obtaining white needle crystals through a series of preparation, obtaining an earthy yellow solid in the step 2) preparation, adding dichloroethane, benzenesulfonyl chloride and a saturated sodium bicarbonate solution in the step 3) and preparing to obtain a dark red oily substance, finally adding a hydrocarbon group and a carboxyl group in a reaction container for mixing and stirring, then adding acetonitrile and concentrated sulfuric acid and carrying out secondary stirring and reaction, further completing the preparation, wherein the whole process is very convenient and fast, the effect of convenient preparation is achieved, and the preparation process from the step 1) to the step 4) is carried out in the reaction container all the time, and the preparation process comprises stirring, heating, cooling, reacting, filtering, suction filtering and the like, so that the preparation method is simple and safe, the preparation method of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid, by adopting a detection instrument to perform detection and sampling test after the preparation in the steps 1) to 4) is finished, the sampling test is performed according to the proportion of the preparation sample range of 1: 100, the preparation process can be finished after the test structure is qualified, the problem of poor qualification rate during the preparation by using the preparation method can be effectively avoided, the preparation method has the advantages that the whole preparation process from the step 1) to the step 4) is very convenient, the practicability and the popularization capability of the preparation method can be effectively enhanced, and the problem that the carboxylic acid can be conveniently prepared in the prior art is solved.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.