阅读说明：本技术 一种硝酸胍的制备方法 (Preparation method of guanidine nitrate ) 是由 施晓刚 于 2019-11-28 设计创作，主要内容包括：本发明提供的硝酸胍的制备方法包括制备粗硝酸胍的方法以及对粗硝酸胍的提纯工艺。制备粗硝酸胍的原料为硝酸铵、双氰胺、尿素以及摩尔质量浓度为0.01～0.1mol/LNaHCO-3以及摩尔质量浓度为0.01～0.1mol/L的HNO-3溶液。本发明提供的硝酸胍的制备方法采用硝酸铵、双氰胺、尿素为原料,成本较低,在制备过程中添加了提纯工艺,制得的硝酸胍的纯度大于99％,酸度小于0.01％,满足医药中间体对硝酸胍的生产需求,克服了传统工艺制备硝酸胍的纯度低以及成本高的缺点。(The preparation method of guanidine nitrate provided by the invention comprises a method for preparing crude guanidine nitrate and a purification process of the crude guanidine nitrate. The raw materials for preparing the crude guanidine nitrate comprise ammonium nitrate, dicyandiamide, urea and 0.01-0.1 mol/LNaHCO 3 And HNO with the molar mass concentration of 0.01-0.1 mol/L 3 And (3) solution. The preparation method of guanidine nitrate provided by the invention adopts ammonium nitrate, dicyandiamide and urea as raw materials, the cost is low, a purification process is added in the preparation process, the purity of the prepared guanidine nitrate is more than 99%, the acidity is less than 0.01%, the production requirement of a medical intermediate on guanidine nitrate is met, and the defects of low purity and high cost of guanidine nitrate prepared by the traditional process are overcome.)

1. The preparation method of guanidine nitrate is characterized by comprising the following steps:

the raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

The method for preparing crude guanidine nitrate comprises the following steps:

(1) providing a urea solution, adding ammonium nitrate at a constant speed under the condition of continuously stirring at 30-40 ℃, heating to 50-60 ℃ after the addition is finished until the ammonium nitrate and the urea are uniformly mixed to prepare a mixed solution A;

(2) adding dicyandiamide into the mixed solution A prepared in the first step at a constant speed of 1-10 g/min, controlling the temperature to be 30-40 ℃, transferring the mixed solution A into a reaction kettle after the addition is finished, and reacting for 2-3 hours at the temperature of 140-150 ℃ to prepare mixed solution B;

(3) performing suction filtration on the mixture B prepared in the step two, and using HNO with the molar mass concentration of 0.01-0.1 mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 50-60 ℃ for 8-10h to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 0.01-0.1 mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 to-5 ℃ and preserving heat for 3-5 hours until all white crystals are separated out;

(2) continuously adding into the white crystal obtained in the step (1)Adding HNO with the concentration of 0.01-0.1 mol/L₃Keeping the temperature of the solution at-3 to-7 ℃ for 3 to 5 hours, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare acid-containing guanidine nitrate;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 0.01-0.1 mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

2. The method for preparing guanidine nitrate according to claim 1, wherein: the mass ratio of the ammonium nitrate to the dicyandiamide is 1: 1-1: 5.

3. The method for preparing guanidine nitrate according to claim 1, wherein: the mass ratio of the urea to the ammonium nitrate is 1: 2-1: 5.

4. The method for preparing guanidine nitrate according to claim 1, wherein: the molar mass concentration of the urea solution is 0.5-5.0 mol/L.

Technical Field

The invention relates to a preparation method of guanidine nitrate, belonging to the technical field of materials.

Background

Guanidine compounds are widely applied in the fields of medicine and chemistry, and are important chemical and pharmaceutical intermediates. In the prior art, the guanidine nitrate is prepared by condensation reaction of molten urea and molten ammonium nitrate, but the reaction has the defects of higher temperature, and has some side reactions such as condensation and cyclization reactions among urea self molecules while the main reaction is carried out, and the by-products generated by the side reactions influence the quality of the guanidine nitrate product. At present, the production method for producing guanidine nitrate by a dicyandiamide method is relatively simple, most enterprises at home and abroad adopt the method to produce guanidine nitrate at present, but the market price of dicyandiamide is relatively high, so that the production cost for producing guanidine nitrate by the dicyandiamide method is relatively high, and the market competition is increasingly violent, so that how to reduce the cost for producing guanidine nitrate by the dicyandiamide method is another big problem in front of the enterprises for producing guanidine nitrate by the dicyandiamide method. Therefore, a method for preparing guanidine nitrate with high efficiency and low cost is needed.

Disclosure of Invention

The invention aims to provide a preparation method of guanidine nitrate, which overcomes the defects in the prior art.

In order to achieve the purpose, the technical scheme adopted by the invention comprises the following steps:

the embodiment of the invention provides a preparation method of guanidine nitrate, which comprises the following steps:

the raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

The method for preparing crude guanidine nitrate comprises the following steps:

(1) providing a urea solution, adding ammonium nitrate at a constant speed under the condition of continuously stirring at 30-40 ℃, heating to 50-60 ℃ after the addition is finished until the ammonium nitrate and the urea are uniformly mixed to prepare a mixed solution A;

(2) adding dicyandiamide into the mixed solution A prepared in the first step at a constant speed of 1-10 g/min, controlling the temperature to be 30-40 ℃, transferring the mixed solution A into a reaction kettle after the addition is finished, and reacting for 2-3 hours at the temperature of 140-150 ℃ to prepare mixed solution B;

(3) performing suction filtration on the mixture B prepared in the step two, and using HNO with the molar mass concentration of 0.01-0.1 mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 50-60 ℃ for 8-10h to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 0.01-0.1 mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 to-5 ℃ and preserving heat for 3-5 hours until all white crystals are separated out;

(2) continuously adding HNO with the concentration of 0.01-0.1 mol/L into the white crystal prepared in the step (1)₃Keeping the temperature of the solution at-3 to-7 ℃ for 3 to 5 hours, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare acid-containing guanidine nitrate;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 0.01-0.1 mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

Further, the mass ratio of the ammonium nitrate to the dicyandiamide is 1: 1-1: 5.

Further, the mass ratio of the urea to the ammonium nitrate is 1: 2-1: 5.

Furthermore, the molar mass concentration of the urea solution is 0.5-5.0 mol/L.

Compared with the prior art, the invention has the advantages that: the preparation method of guanidine nitrate provided by the invention adopts ammonium nitrate, dicyandiamide and urea as raw materials, the cost is low, a purification process is added in the preparation process, the purity of the prepared guanidine nitrate is more than 99%, the acidity is less than 0.01%, and the pharmaceutical intermediate meets the production requirement of guanidine nitrate.

Detailed Description

In view of the deficiencies in the prior art, the inventors of the present invention have made extensive studies and extensive practices to provide technical solutions of the present invention. The technical solution, its implementation and principles, etc. will be further explained as follows.

The embodiment of the invention provides a preparation method of guanidine nitrate, which comprises the following steps:

the raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

The method for preparing crude guanidine nitrate comprises the following steps:

(1) providing a urea solution, adding ammonium nitrate at a constant speed under the condition of continuously stirring at 30-40 ℃, heating to 50-60 ℃ after the addition is finished until the ammonium nitrate and the urea are uniformly mixed to prepare a mixed solution A;

(2) adding dicyandiamide into the mixed solution A prepared in the first step at a constant speed of 1-10 g/min, controlling the temperature to be 30-40 ℃, transferring the mixed solution A into a reaction kettle after the addition is finished, and reacting for 2-3 hours at the temperature of 140-150 ℃ to prepare mixed solution B;

(3) performing suction filtration on the mixture B prepared in the step two, and using HNO with the molar mass concentration of 0.01-0.1 mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 50-60 ℃ for 8-10h to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 0.01-0.1 mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 to-5 ℃ and preserving heat for 3-5 hours until all white crystals are separated out;

(2) continuously adding HNO with the concentration of 0.01-0.1 mol/L into the white crystal prepared in the step (1)₃Keeping the temperature of the solution at-3 to-7 ℃ for 3 to 5 hours, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare acid-containing guanidine nitrate;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 0.01-0.1 mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

Further, the mass ratio of the ammonium nitrate to the dicyandiamide is 1: 1-1: 5.

Further, the mass ratio of the urea to the ammonium nitrate is 1: 2-1: 5.

Furthermore, the molar mass concentration of the urea solution is 0.5-5.0 mol/L.

The technical solution of the present invention is further explained below with reference to several examples.

Example 1

The raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

(1) Providing 30mL of 1.0mol/L urea solution, adding 10g of ammonium nitrate at a constant speed under the condition of continuous stirring at 40 ℃, and after the addition is finished, heating to 50 ℃ until the ammonium nitrate and the urea are uniformly mixed to obtain a mixed solution A;

(2) adding 20g of bis (cyanamide) into the mixed solution A prepared in the first step at a constant speed, controlling the adding speed to be 5g/mins and the temperature to be 35 ℃, transferring the mixed solution A into a reaction kettle after the adding is finished, and reacting for 2 hours at the temperature of 140 ℃ to prepare a mixed solution B;

(3) filtering the mixture B prepared in the second step, and using 100mL of HNO with the molar mass concentration of 0.01mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 60 ℃ for 8 hours to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 20mL0.01mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 ℃ and preserving heat for 3 hours until all white crystals are separated out;

(2) continuously adding HNO with the concentration of 30mL and 0.01/L into the white crystals prepared in the step (1)₃Keeping the solution at-3 ℃ for 3h, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare guanidine nitrate containing acid;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 30mL of 0.01/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

Example 2

The raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

(1) Providing 10mL of 5.0mol/L urea solution, adding 10g of ammonium nitrate at a constant speed under the condition of continuous stirring at 40 ℃, and after the addition is finished, heating to 50 ℃ until the ammonium nitrate and the urea are uniformly mixed to obtain mixed solution A;

(2) adding 50g of dicyandiamide into the mixed solution A prepared in the step one at a constant speed of 5g/mins, controlling the temperature to be 35 ℃, transferring the mixed solution A into a reaction kettle after the addition is finished, and reacting for 2 hours at the temperature of 140 ℃ to prepare a mixed solution B;

(3) filtering the mixture B prepared in the second step, and using 100mL of HNO with the molar mass concentration of 0.5mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 60 ℃ for 8 hours to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 40mL0.1mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 ℃ and preserving heat for 3 hours until all white crystals are separated out;

(2) adding HNO with the concentration of 30mL and 0.01mol/L into the white crystals prepared in the step (1)₃Keeping the solution at-3 ℃ for 3h, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare guanidine nitrate containing acid;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 50mL of 0.01mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

Example 3

The raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

(1) Providing 30mL of 1.0mol/L urea solution, adding 10g of ammonium nitrate at a constant speed under the condition of continuous stirring at 40 ℃, and after the addition is finished, heating to 50 ℃ until the ammonium nitrate and the urea are uniformly mixed to obtain a mixed solution A;

(2) adding 20g of dicyandiamide into the mixed solution A prepared in the step one at a constant speed, wherein the adding speed is 1-10 g/mins, the temperature is controlled to be 35 ℃, transferring the mixed solution A into a reaction kettle after the adding is finished, and reacting for 2 hours at the temperature of 140 ℃ to prepare mixed solution B;

(3) filtering the mixture B prepared in the second step, and using 100mL of HNO with the molar mass concentration of 0.01mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at the temperature of 60 ℃ for 8 hours to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 20mL0.01mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 ℃ and preserving heat for 3 hours until all white crystals are separated out;

(2) go to stepAdding HNO with the concentration of 30mL and 0.05mol/L into the white crystals prepared in the step (1)₃Keeping the solution at-3 ℃ for 3h, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare guanidine nitrate containing acid;

(3) adding deionized water into the obtained acid-containing guanidine nitrate at normal temperature for cleaning for 3-5 times, and then using 30mL of 0.05mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

Example 4

The raw materials for preparing guanidine nitrate comprise: ammonium nitrate, dicyandiamide, urea and ammonia water with the molar mass concentration of 0.01-0.1 mol/LNaHCO₃And HNO with the molar mass concentration of 0.01-0.1 mol/L₃And (3) solution.

(1) Providing 30mL of 0.5mol/L urea solution, adding 10g of ammonium nitrate at a constant speed under the condition of continuous stirring at 40 ℃, and after the addition is finished, heating to 50 ℃ until the ammonium nitrate and the urea are uniformly mixed to obtain a mixed solution A;

(2) adding 40g of dicyandiamide into the mixed solution A prepared in the step one at a constant speed of 10g/mins, controlling the temperature to be 40 ℃, transferring the mixed solution A into a reaction kettle after the adding is finished, and reacting for 2 hours at the temperature of 140 ℃ to prepare a mixed solution B;

(3) filtering the mixture B prepared in the second step, and using 100mL of HNO with the molar mass concentration of 0.05mol/L₃Cleaning the solution for 3-5 times, and then drying the solution at 50 ℃ for 9 hours to obtain the crude guanidine nitrate;

and (3) purifying the crude guanidine nitrate:

(1) providing HNO with the molar mass concentration of 20mL0.05mol/L₃Dropwise adding the solution into crude guanidine nitrate under continuous stirring to prepare a mixed solution C, and then cooling the mixed solution C to-1 ℃ and preserving heat for 3 hours until all white crystals are separated out;

(2) adding HNO with the concentration of 10mL and 0.1mol/L into the white crystals prepared in the step (1)₃Keeping the solution at-3 ℃ for 3h, wherein the process is called a crystal growing process, and after the crystal growing is finished, recovering nitric acid to prepare guanidine nitrate containing acid;

(3) adding the obtained acid-containing guanidine nitrate into deionized water at normal temperatureWashing with water for 3-5 times, and then washing with 40mL of 0.1mol/LNaHCO₃And cleaning and drying to obtain the guanidine nitrate.

It should be understood that the above-mentioned embodiments are merely illustrative of the technical concepts and features of the present invention, which are intended to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and therefore, the protection scope of the present invention is not limited thereby. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.