Preparation method of 2, 6-dimethylphenylhydrazine inorganic acid salt

Abstract

The invention relates to a preparation method of 2, 6-dimethylphenylhydrazine inorganic acid salt, which comprises the steps of diazotization, reduction, purification and salification. In the steps of diazotization and reduction, concentrated hydrochloric acid is adopted to keep the reaction liquid to be strongly acidic, so that the reaction can be smoothly and completely carried out; in the reduction step, zinc powder-concentrated hydrochloric acid is adopted as a reducing agent to replace sodium thiosulfate, sodium hydrogen sulfite, stannous chloride-hydrochloric acid and the like, so that the reduction performance is good, the yield is high, the reaction time is shortened, impurities such as zinc hydroxide generated after the reaction are convenient to remove, and the product has few impurities and high purity; acetone is used for leaching in the salifying step, so that the purity of the product is improved, and the appearance of the product is ensured. The preparation method is stable and reliable in process, easy to operate and high in product purity, and completely meets the requirements of the market on the 2, 6-dimethylphenylhydrazine inorganic acid salt.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of organic compounds, in particular to a method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt. Background Art

[0002] In the dye and pharmaceutical manufacturing industries, 2,6-dimethylphenylhydrazine inorganic acid salt is an important organic synthesis intermediate with an increasing market demand and broad market prospects. However, the existing preparation methods of 2,6-dimethylphenylhydrazine inorganic acid salt have many serious problems, which greatly limit its application in actual production.

[0003] On the one hand, the products obtained by the existing preparation methods have high impurity content. This not only affects the quality of the product, but may also cause a series of adverse consequences during subsequent use. For example, in dye production, impurities may cause impure colors and poor dyeing effects; in pharmaceutical manufacturing, impurities may affect the efficacy and safety of drugs. On the other hand, low product purity is also a major drawback of the existing preparation methods. Low-purity 2,6-dimethylphenylhydrazine inorganic acid salts cannot meet the demand of the high-end market for high-quality organic synthesis intermediates. In some pharmaceutical research and development and production fields with extremely high purity requirements, low-purity products may not be used at all. In addition, the products prepared by the existing methods have poor stability. This means that during storage and transportation, the product is prone to deterioration, reducing its service life and value. At the same time, poor stability also brings additional costs and risks to manufacturers.

[0004] The existing preparation method of 2,6-dimethylphenylhydrazine inorganic acid salt can no longer meet the market demand due to the problems of high impurity content, low purity, poor stability and low yield of the product. Therefore, it is urgent to develop a new and efficient 2,6-dimethylphenylhydrazine inorganic acid salt. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt with high purity, large yield and good stability.

[0006] The present invention solves the technical problem by adopting the following technical solutions:

[0007] A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt comprises the following steps:

[0008] S1. Diazotization: 2,6-dimethylaniline and 30% to 40% concentrated hydrochloric acid were mixed and cooled to 0 to 5°C, and a 35% sodium nitrite aqueous solution was added while stirring, and the mixture was reacted for 1 to 1.5 hours to obtain a reaction solution;

[0009] S2, reduction: add 30% to 40% by mass of concentrated hydrochloric acid, water and zinc powder to the reaction solution, keep the temperature at 15 to 20°C until the reaction solution turns grayish white, then add 20 to 30% by mass of sodium hydroxide solution until the pH of the reaction solution is 10, then keep warm at 5 to 10°C for 1 to 2 hours, precipitate crystals, and filter to obtain crude 2,6-dimethylphenylhydrazine;

[0010] S3, purification: dissolve the crude 2,6-dimethylphenylhydrazine in water, heat to 60°C to completely dissolve it, then add activated carbon for decolorization for 15 to 25 minutes, filter hot to obtain a colorless filtrate, keep warm at 5 to 10°C for 1 to 2 hours, precipitate crystals, and filter to obtain pure 2,6-dimethylphenylhydrazine;

[0011] S4. Salt formation: dissolve the pure 2,6-dimethylphenylhydrazine in an acidic solution with a mass fraction of 30% to 50%, stir at 60 to 70°C until the reaction solution precipitates crystals, cool to 20°C, filter, rinse the filter cake with acetone, and dry to obtain the finished product of 2,6-dimethylphenylhydrazine inorganic acid salt.

[0012] Moreover, in step S1, the weight volume ratio of the 2,6-dimethylaniline to the concentrated hydrochloric acid is 1:3-5.

[0013] Moreover, the weight ratio of the 2,6-dimethylaniline to the sodium nitrite aqueous solution is 3-6:1-4.

[0014] Moreover, in step S2, the volume ratio of concentrated hydrochloric acid to water is 1:1, and the weight volume ratio of concentrated hydrochloric acid to zinc powder is 15-16:4, g / ml.

[0015] Moreover, the weight ratio of the crude 2,6-dimethylphenylhydrazine to water is 1:15-25.

[0016] Furthermore, the acidic solution includes sulfuric acid, hydrochloric acid, oxalic acid and phosphoric acid.

[0017] Moreover, the weight volume ratio of the pure 2,6-dimethylphenylhydrazine to the acid solution is 100-150:100-180, g / ml.

[0018] The advantages and positive effects of the present invention are:

[0019] 1. In the preparation method of the present invention, concentrated hydrochloric acid is used to keep the reaction solution strongly acidic during the diazotization and reduction processes to ensure that the reaction proceeds smoothly and completely.

[0020] 2. In the reduction process of the preparation method of the present invention, zinc powder-concentrated hydrochloric acid is used as a reducing agent instead of sodium thiosulfate, sodium bisulfite, stannous chloride-hydrochloric acid, etc.; not only is the reduction performance good, the yield is high, the reaction time is shortened, and impurities such as zinc hydroxide generated after the reaction are easy to remove, so that the product has fewer impurities and higher purity.

[0021] 3. The preparation method of the present invention uses acetone for elution during the salt formation process, which not only improves the purity of the product but also ensures the appearance of the product.

[0022] 4. The preparation method of the present invention is stable and reliable, easy to operate, and has high product purity. The content of the product measured by high performance liquid chromatography is ≥99.2%, and the yield is ≥42%, which fully meets the market demand for 2,6-dimethylphenylhydrazine inorganic acid salt. DETAILED DESCRIPTION

[0023] The present invention is further described in detail below through specific examples. The following examples are only illustrative and not restrictive, and the protection scope of the present invention cannot be limited thereto.

[0024] Example 1

[0025] A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt, this embodiment is a method for preparing 2,6-dimethylphenylhydrazine phosphate, comprising the following steps:

[0026] S1, diazotization: add 500g 2,6-dimethylaniline and 1500ml 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 857g 35% sodium nitrite aqueous solution while stirring, keep the temperature at 2°C and react for 1 hour;

[0027] S2, reduction: add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 480g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete and the reaction solution turns grayish white, then add 20% sodium hydroxide solution until the pH value of the reaction solution is 10, keep warm at 5°C for 1 hour, precipitate crystals, and filter to obtain 295g of crude 2,6-dimethylphenylhydrazine;

[0028] S3, purification: 295g of crude 2,6-dimethylphenylhydrazine was dissolved in 5900g of water, heated to 60°C to completely dissolve it, and then an appropriate amount of activated carbon was added for decolorization for 20 minutes, and hot filtration was performed to obtain a colorless filtrate, which was kept at 5°C for 1 hour to precipitate crystals, and filtered to obtain 238g of pure 2,6-dimethylphenylhydrazine;

[0029] S4, salt formation: 238g of pure 2,6-dimethylphenylhydrazine was dissolved in 405ml of 40% phosphoric acid, stirred at 65°C until the reaction solution precipitated crystals, cooled to 20°C, filtered, the filter cake was rinsed with acetone, and dried to obtain 383g of 2,6-dimethylphenylhydrazine phosphate product with a content of 99.3% and a yield of 42.7%.

[0030] Example 2

[0031] A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt, this embodiment is a method for preparing 2,6-dimethylphenylhydrazine oxalate, comprising the following steps:

[0032] S1, diazotization: add 500g 2,6-dimethylaniline and 1500ml 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 857g 35% sodium nitrite aqueous solution while stirring, keep the temperature at 0-5°C and react for 1.5 hours;

[0033] S2, reduction: add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 480g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns grayish white, then add 30% sodium hydroxide solution until the pH value of the reaction solution is 10, keep warm at 5°C for 2 hours, precipitate crystals, and filter to obtain 292g of crude 2,6-dimethylphenylhydrazine;

[0034] S3, purification: 292g of crude 2,6-dimethylphenylhydrazine was dissolved in 5840g of water, heated to 60°C to completely dissolve it, and then an appropriate amount of activated carbon was added for decolorization for 20 minutes, and hot filtration was performed to obtain a colorless filtrate, which was kept at 5°C for 2 hours to precipitate crystals, and filtered to obtain 241g of pure 2,6-dimethylphenylhydrazine;

[0035] S4, salt formation: 241 g of pure 2,6-dimethylphenylhydrazine was dissolved in 509 ml of 30% oxalic acid, and the reaction solution was stirred at 65° C. until crystals precipitated, and the reaction solution was cooled to 20° C., filtered, and the filter cake was rinsed with acetone. After drying, 361 g of 2,6-dimethylphenylhydrazine oxalate was obtained, with a content of 99.1% and a yield of 42.2%.

[0036] Example 3

[0037] A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt, this embodiment is a method for preparing 2,6-dimethylphenylhydrazine sulfate, comprising the following steps:

[0038] S1, diazotization: add 500g 2,6-dimethylaniline and 1500ml 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 857g 35% sodium nitrite aqueous solution while stirring, keep the temperature at 0-5°C and react for 1.5 hours;

[0039] S2, reduction: add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 480g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns grayish white, then add 30% sodium hydroxide solution to the reaction solution pH value of 10, keep warm at 5°C for 2 hours, precipitate crystals, filter to obtain 290g of 2,6-dimethylphenylhydrazine crude product;

[0040] S3, purification: 290g of crude 2,6-dimethylphenylhydrazine was dissolved in 5800g of water, heated to 60°C to completely dissolve it, and then an appropriate amount of activated carbon was added for decolorization for 20 minutes, and hot filtration was performed to obtain a colorless filtrate, which was kept at 5°C for 2 hours to precipitate crystals, and filtered to obtain 235g of pure 2,6-dimethylphenylhydrazine;

[0041] S4, salt formation: 235g of pure 2,6-dimethylphenylhydrazine was dissolved in 405ml of 40% sulfuric acid, and the reaction solution was stirred at 65°C until crystals precipitated, cooled to 20°C, filtered, and the filter cake was rinsed with acetone. After drying, 377g of 2,6-dimethylphenylhydrazine sulfate was obtained, with a content of 99.3% and a yield of 42.7%.

[0042] Example 4

[0043] A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt, this embodiment is a method for preparing 2,6-dimethylphenylhydrazine hydrochloride, comprising the following steps:

[0044] S1, diazotization: add 200g 2,6-dimethylaniline and 600ml 37% concentrated hydrochloric acid into a 5L three-necked flask, cool to 2°C with ice salt, add 343g 35% sodium nitrite aqueous solution while stirring, keep the temperature at 2°C and react for 1.5 hours;

[0045] S2, reduction: add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 195g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns grayish white, then add 25% sodium hydroxide solution until the pH value of the reaction solution is 10, keep warm at 5°C for 1.5 hours, precipitate crystals, and filter to obtain 120g of crude 2,6-dimethylphenylhydrazine;

[0046] S3, purification: 120g of crude 2,6-dimethylphenylhydrazine was dissolved in 2400g of water, heated to 60°C to completely dissolve it, and then an appropriate amount of activated carbon was added for decolorization for 20 minutes, and hot filtration was performed to obtain a colorless filtrate, which was kept at 5°C for 1.5 hours to precipitate crystals, and filtered to obtain 100g of pure 2,6-dimethylphenylhydrazine;

[0047] S4, salt formation: 100g of pure 2,6-dimethylphenylhydrazine was dissolved in 69ml of 37% hydrochloric acid, stirred at 65°C until the reaction solution precipitated crystals, cooled to 20°C, filtered, the filter cake was rinsed with acetone, and dried to obtain 110g of 2,6-dimethylphenylhydrazine hydrochloride product with a content of 99.2% and a yield of 39.5%.

[0048] Although the embodiments of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments.

Claims

1. A method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt, characterized in that: The steps include: S1. Diazotization: 2,6-dimethylaniline and 30% to 40% concentrated hydrochloric acid were mixed and cooled to 0 to 5°C, and a 35% sodium nitrite aqueous solution was added while stirring, and the mixture was reacted for 1 to 1.5 hours to obtain a reaction solution; S2, reduction: add 30% to 40% by mass of concentrated hydrochloric acid, water and zinc powder to the reaction solution, keep the temperature at 15 to 20°C until the reaction solution turns grayish white, then add 20 to 30% by mass of sodium hydroxide solution until the pH of the reaction solution is 10, then keep warm at 5 to 10°C for 1 to 2 hours, precipitate crystals, and filter to obtain crude 2,6-dimethylphenylhydrazine; S3, purification: dissolve the crude 2,6-dimethylphenylhydrazine in water, heat to 60°C to completely dissolve it, then add activated carbon for decolorization for 15 to 25 minutes, filter hot to obtain a colorless filtrate, keep warm at 5 to 10°C for 1 to 2 hours, precipitate crystals, and filter to obtain pure 2,6-dimethylphenylhydrazine; S4. Salt formation: dissolve the pure 2,6-dimethylphenylhydrazine in an acidic solution with a mass fraction of 30% to 50%, stir at 60 to 70°C until the reaction solution precipitates crystals, cool to 20°C, filter, rinse the filter cake with acetone, and dry to obtain the finished product of 2,6-dimethylphenylhydrazine inorganic acid salt.

2. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, wherein: In step S1, the weight volume ratio of the 2,6-dimethylaniline to concentrated hydrochloric acid is 1:3-5.

3. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, characterized in that: The weight ratio of the 2,6-dimethylaniline to the sodium nitrite aqueous solution is 3-6:1-4.

4. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, characterized in that: In step S2, the volume ratio of concentrated hydrochloric acid to water is 1:1, and the weight volume ratio of concentrated hydrochloric acid to zinc powder is 15-16:4, g / ml.

5. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, characterized in that: The weight ratio of the crude 2,6-dimethylphenylhydrazine to water is 1:15-25.

6. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, characterized in that: The acidic solution includes sulfuric acid, hydrochloric acid, oxalic acid and phosphoric acid.

7. The method for preparing 2,6-dimethylphenylhydrazine inorganic acid salt according to claim 1, characterized in that: The weight-to-volume ratio of pure 2,6-dimethylphenylhydrazine to the acid solution is 100-150:100-180, g / ml.