Preparation method of 3-aminopyridine

Abstract

The invention relates to a preparation method of 3-aminopyridine. Nicotinamide is used as an initial raw material, a Huffman degradation reaction is carried out in a sodium hypochlorite and sodium hydroxide solution, and a final 3-aminopyridine product is obtained through reaction cooling treatment, alkali adjustment, heating reaction treatment, vacuum filtration drying and secondary recrystallization drying. The whole reaction conditions are mild and easy to control, the operation is simple, the purity of 3-aminopyridine reaches 99% or above, mainly, the post-treatment method is simple, convenient and easy to operate, the total yield can reach 90% or above, and the method is a post-treatment technology suitable for industrial production and application.

Description

technical field

[0001] The invention relates to the field of synthesis of chemical raw materials, in particular to a preparation method of 3-aminopyridine. Background technique

[0002] Aminopyridine is an important class of derivatives of pyridine, which is widely used in the field of chemical engineering. With the continuous development of science and technology, the application scope of aminopyridine compounds shows an upward trend year by year. Among them, 3-aminopyridine is one of the main aminopyridine compounds, mainly used in the synthesis of pesticides and pharmaceutical intermediates. At present, the methods for preparing 3-aminopyridine mainly include the following technological routes: one is catalytic synthesis of halogenated pyridine compounds; the other is synthesis by catalytic reduction of nitropyridine; Synthesis; the fourth is synthesized by methylpyridine through acid amine and then Hoffman degradation; the fifth is synthesized by formamide directly thr...

Examples

Embodiment 7

[0029] A kind of preparation method of 3-aminopyridine, its steps are:

[0030] S1: firstly, cooling and stirring 1200g of sodium hypochlorite solution with an available chlorine content of 3%;

[0031] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 60g of solid nicotinamide into it, while keeping the temperature of the reaction solution at 0°C to 20°C, so as to carry out the low temperature reaction for 10min to 120min, and keep stirring until the reaction liquid is clear;

[0032] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 150g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly raise the temperature to control the temperature at 50°C ~80℃, keep warm for 0.5h~3h;

[0033] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is...

Embodiment 12

[0037] A kind of preparation method of 3-aminopyridine, its steps are:

[0038] S1: firstly, 580 g of sodium hypochlorite solution with an available chlorine content of 7.5% is cooled and stirred;

[0039] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 75g of solid nicotinamide into it, and at the same time keep the temperature of the reaction solution at 5°C-10°C for low-temperature reaction for 30min-60min, and keep stirring until the reaction liquid is clear;

[0040] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 72g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly heat it up to keep the temperature at 70°C ~75℃, keep warm for 1h~1.5h;

[0041] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is ≥ 98%, and the reaction en...

Embodiment 14

[0045] A kind of preparation method of 3-aminopyridine, its steps are:

[0046] S1: firstly, the 365g sodium hypochlorite solution with 12% available chlorine content is cooled and stirred;

[0047] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 75g of solid nicotinamide into it, while keeping the temperature of the reaction solution at 5°C for low-temperature reaction for 40 minutes, and keep stirring until the reaction solution is clear;

[0048] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 45g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly raise the temperature to control the temperature at 70°C , and keep warm for 1h;

[0049] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is ≥ 98%, and the reaction ends;

[0050] ...

technical field

[0001] The invention relates to the field of synthesis of chemical raw materials, in particular to a preparation method of 3-aminopyridine. Background technique

[0002] Aminopyridine is an important class of derivatives of pyridine, which is widely used in the field of chemical engineering. With the continuous development of science and technology, the application scope of aminopyridine compounds shows an upward trend year by year. Among them, 3-aminopyridine is one of the main aminopyridine compounds, mainly used in the synthesis of pesticides and pharmaceutical intermediates. At present, the methods for preparing 3-aminopyridine mainly include the following technological routes: one is catalytic synthesis of halogenated pyridine compounds; the other is synthesis by catalytic reduction of nitropyridine; Synthesis; the fourth is synthesized by methylpyridine through acid amine and then Hoffman degradation; the fifth is synthesized by formamide directly thr...

Examples

Embodiment 7

[0029] A kind of preparation method of 3-aminopyridine, its steps are:

[0030] S1: firstly, cooling and stirring 1200g of sodium hypochlorite solution with an available chlorine content of 3%;

[0031] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 60g of solid nicotinamide into it, while keeping the temperature of the reaction solution at 0°C to 20°C, so as to carry out the low temperature reaction for 10min to 120min, and keep stirring until the reaction liquid is clear;

[0032] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 150g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly raise the temperature to control the temperature at 50°C ~80℃, keep warm for 0.5h~3h;

[0033] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is...

Embodiment 12

[0037] A kind of preparation method of 3-aminopyridine, its steps are:

[0038] S1: firstly, 580 g of sodium hypochlorite solution with an available chlorine content of 7.5% is cooled and stirred;

[0039] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 75g of solid nicotinamide into it, and at the same time keep the temperature of the reaction solution at 5°C-10°C for low-temperature reaction for 30min-60min, and keep stirring until the reaction liquid is clear;

[0040] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 72g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly heat it up to keep the temperature at 70°C ~75℃, keep warm for 1h~1.5h;

[0041] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is ≥ 98%, and the reaction en...

Embodiment 14

[0045] A kind of preparation method of 3-aminopyridine, its steps are:

[0046] S1: firstly, the 365g sodium hypochlorite solution with 12% available chlorine content is cooled and stirred;

[0047] S2: When the temperature of the sodium hypochlorite solution is lower than 20°C, add 75g of solid nicotinamide into it, while keeping the temperature of the reaction solution at 5°C for low-temperature reaction for 40 minutes, and keep stirring until the reaction solution is clear;

[0048] S3: Test the pH value of the reaction solution and use HPLC to detect whether the raw materials are completely converted, then add 45g of 10% sodium hydroxide solution, adjust the reaction solution to strong alkalinity, transfer it to a water bath and slowly raise the temperature to control the temperature at 70°C , and keep warm for 1h;

[0049] S4: During the reaction period of step S3, regular sampling by HPLC is performed until the product content is ≥ 98%, and the reaction ends;

[0050] ...

Images