Preparation method of 2-bromophenylhydrazine sulfate

Abstract

The invention relates to a preparation method of 2-bromophenylhydrazine sulfate. The preparation method comprises the following steps of diazotization, reduction, purification and salt formation. In the diazotization and reduction steps, concentrated hydrochloric acid is adopted, so that a reaction liquid is kept to be strong acidic, and the reaction is kept smoothly and completely. In the reduction step, zinc powder and the concentrated hydrochloric acid are used as reducing agents to replace sodium thiosulfate, sodium hydrogen sulfite, stannous chloride and hydrochloric acid and the like, so that good reducing property and high yield are realized, the reaction time is shortened, impurities such as zinc hydroxide and the like generated after the reaction are convenient to remove, and a product is few in impurities and high in purity. In the salt formation step, acetone is used for leaching, so that not only is the purity of the product increased, but also the appearance of the product is ensured. The preparation method is stable and reliable in process, easy to operate, high in product purity (larger than or equal to 99.2% measured by a high performance liquid chromatography), high in yield (larger than or equal to 42%) and capable of completely meeting the requirement of the market for 2-bromophenylhydrazine sulfate.

Description

technical field

[0001] The invention relates to the technical field of preparation of organic compounds, in particular to a preparation method of 2-bromophenylhydrazine sulfate. Background technique

[0002] As an important organic synthesis intermediate, 2-bromophenylhydrazine sulfate is widely used in the pharmaceutical manufacturing industry and has a broad market prospect. And the prepared product of existing 2-bromophenylhydrazine sulfate has high impurity content, low purity, poor stability and small output, which cannot meet the needs of the market. Contents of the invention

[0003] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing 2-bromophenylhydrazine sulfate with high purity, large output and good stability.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A preparation method of 2-bromophenylhydrazine sulfate, the step...

Examples

Embodiment 1

[0018] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0019] ⑴ diazotization

[0020] Add 50g of 2-bromoaniline and 150ml of 37% concentrated hydrochloric acid into a 1L three-necked flask, cool to 2°C with ice salt, add 65g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1 hour.

[0021] ⑵ reduction

[0022] Add 450ml of 37% concentrated hydrochloric acid, 450ml of water and 120g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 20% sodium hydroxide solution until the pH value of the reaction solution is 10, After 1 hour of heat preservation at 5°C, crystals were precipitated, and 26 g of crude 2-bromophenylhydrazine was obtained by filtration.

[0023] ⑶ Purification

[0024] Dissolve 26g of crude 2-bromophenylhydrazine in 520g of water, heat to 60°C to dissolve it completely, add an ap...

Embodiment 2

[0028] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0029] ⑴ diazotization

[0030] Add 200g of 2-bromoaniline and 600ml of 37% concentrated hydrochloric acid into a 5L three-necked flask, cool to 2°C with ice salt, add 270g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0031] ⑵ reduction

[0032] 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 off-white, then add 25% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 1.5 hours, crystals were precipitated, and 118g of crude 2-bromophenylhydrazine was obtained by filtration.

[0033] ⑶ Purification

[0034] Dissolve 118g of crude 2-bromophenylhydrazine in 2360g of water, heat to 60°C to dissolve it completely, then add an appr...

Embodiment 3

[0038] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0039] ⑴ diazotization

[0040] Add 500g of 2-bromoaniline and 1500ml of 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 650g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature between 0 and 5°C for 1.5 hours.

[0041] ⑵ reduction

[0042] 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 off-white, then add 30% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 2 hours, crystals were precipitated, and 270 g of crude 2-bromophenylhydrazine was obtained by filtration.

[0043] ⑶ Purification

[0044] Dissolve 270g of crude 2-bromophenylhydrazine in 5400g of water, heat to 60°C to dissolve it completely, then...

technical field

[0001] The invention relates to the technical field of preparation of organic compounds, in particular to a preparation method of 2-bromophenylhydrazine sulfate. Background technique

[0002] As an important organic synthesis intermediate, 2-bromophenylhydrazine sulfate is widely used in the pharmaceutical manufacturing industry and has a broad market prospect. And the prepared product of existing 2-bromophenylhydrazine sulfate has high impurity content, low purity, poor stability and small output, which cannot meet the needs of the market. Contents of the invention

[0003] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing 2-bromophenylhydrazine sulfate with high purity, large output and good stability.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A preparation method of 2-bromophenylhydrazine sulfate, the step...

Examples

Embodiment 1

[0018] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0019] ⑴ diazotization

[0020] Add 50g of 2-bromoaniline and 150ml of 37% concentrated hydrochloric acid into a 1L three-necked flask, cool to 2°C with ice salt, add 65g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1 hour.

[0021] ⑵ reduction

[0022] Add 450ml of 37% concentrated hydrochloric acid, 450ml of water and 120g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 20% sodium hydroxide solution until the pH value of the reaction solution is 10, After 1 hour of heat preservation at 5°C, crystals were precipitated, and 26 g of crude 2-bromophenylhydrazine was obtained by filtration.

[0023] ⑶ Purification

[0024] Dissolve 26g of crude 2-bromophenylhydrazine in 520g of water, heat to 60°C to dissolve it completely, add an ap...

Embodiment 2

[0028] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0029] ⑴ diazotization

[0030] Add 200g of 2-bromoaniline and 600ml of 37% concentrated hydrochloric acid into a 5L three-necked flask, cool to 2°C with ice salt, add 270g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0031] ⑵ reduction

[0032] 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 off-white, then add 25% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 1.5 hours, crystals were precipitated, and 118g of crude 2-bromophenylhydrazine was obtained by filtration.

[0033] ⑶ Purification

[0034] Dissolve 118g of crude 2-bromophenylhydrazine in 2360g of water, heat to 60°C to dissolve it completely, then add an appr...

Embodiment 3

[0038] A preparation method for 2-bromophenylhydrazine sulfate, comprising the following steps:

[0039] ⑴ diazotization

[0040] Add 500g of 2-bromoaniline and 1500ml of 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 650g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature between 0 and 5°C for 1.5 hours.

[0041] ⑵ reduction

[0042] 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 off-white, then add 30% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 2 hours, crystals were precipitated, and 270 g of crude 2-bromophenylhydrazine was obtained by filtration.

[0043] ⑶ Purification

[0044] Dissolve 270g of crude 2-bromophenylhydrazine in 5400g of water, heat to 60°C to dissolve it completely, then...