Preparation method of trihydroxymethyl aminomethane

Abstract

The invention discloses a preparation method of tris (hydroxymethyl) aminomethane, which comprises the following steps: S1, adding tris (hydroxymethyl) nitromethane, methanol, dichloromethane and raney nickel into a reaction kettle, replacing with nitrogen and ammonia gas for 4-6 times, and starting a stirrer; s2, introducing hydrogen into the reaction kettle in the step S1, slowly raising the reaction temperature to 58-60 DEG C, adjusting the pressure to 2.2-2.6 MPa, reacting for 2-3 hours, adding activated carbon, cooling to 0-2 DEG C, separating out crystals, and filtering to obtain a trihydroxymethyl aminomethane crude product; s3, adding the trihydroxymethyl aminomethane crude product obtained in the step S2 into a refining kettle, then adding methanol and water, heating to 60-80 DEG C, stirring for 1-2 hours, cooling to separate out crystals, filtering and drying to obtain a trihydroxymethyl aminomethane finished product; the method disclosed by the invention is beneficial to improving the yield and the purity of the tris (hydroxymethyl) aminomethane.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a preparation method of tris(hydroxymethyl)aminomethane. Background Art

[0002] Tris(hydroxymethyl)aminomethane is an important biological, chemical and pharmaceutical intermediate, which is widely used in acute metabolic and respiratory acidosis. As a basic buffer, it has a good buffering effect on metabolic enzyme poisoning and enzyme activity reactions. At the same time, it is often used in detection products such as biochemical diagnostic kits, DNA / RNA extraction kits and PCR diagnostic kits. At present, the method for preparing tris(hydroxymethyl)aminomethane includes condensing to form tris(hydroxymethyl)nitromethane at a certain temperature. After the condensation reaction is completed, directly under certain temperature, pressure, solvent and catalyst, through a hydrogenation reduction reaction, and then through crystallization and recrystallization to make tris(hydroxymethyl)aminomethane. However, the product yield is relatively low; in addition, the purity of the currently prepared tris(hydroxymethyl)aminomethane still needs to be improved. Summary of the Invention

[0003] The purpose of the present invention is to provide a preparation method of tris(hydroxymethyl)aminomethane, which can effectively solve the technical problems mentioned in the background art.

[0004] To achieve the above purpose, the present invention provides the following technical solutions: A preparation method of tris(hydroxymethyl)aminomethane, which includes the following steps. S1. Add tris(hydroxymethyl)nitromethane, methanol, dichloromethane and Raney nickel into the reaction kettle, displace with nitrogen and ammonia for 4 - 6 times, start the stirrer, control the reaction temperature in the reaction kettle to be 28 - 32 °C, and the pressure to be 1.6 - 2.2 MPa. Among them, the mass ratio of tris(hydroxymethyl)nitromethane, methanol, dichloromethane and Raney nickel is 10:40:1:1. S2. Pass hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 58 - 60 °C, adjust the pressure to 2.2 - 2.6 MPa. After reacting for 2 - 3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane. S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into the refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane.

[0005] Preferably, water is added to step S1, and the molar ratio of water to methanol is 1:6.

[0006] Preferably, the method for preparing activated carbon in step S2 includes: mixing an organic solid material, phosphoric acid, and water for primary carbonization at a temperature of 160-180 °C for 36-45 h; after the primary carbonization, performing 1-3 times of secondary carbonization, and then mixing the finally obtained pre-mixture with an alkaline activator for alkali activation treatment to obtain the activated carbon.

[0007] Preferably, the temperature of the secondary carbonization is 500-560 °C and the time is 1-2 h; the temperature of the alkali activation treatment is 750-800 °C and the time is 45-60 min.

[0008] Preferably, the organic solid material includes wood chips, lignite, and crop residues.

[0009] Preferably, hydrogen is introduced into the reaction kettle in step S1, the reaction temperature is slowly raised to 60 °C, the pressure is adjusted to 2.5 MPa, and the reaction is carried out for 3 hours.

[0010] Compared with the prior art, the beneficial effects of the present invention are as follows: Compared with the traditional direct hydrogenation method for preparing tris(hydroxymethyl)aminomethane, the tris(hydroxymethyl)aminomethane prepared by the present invention has a high yield, stable performance, and is suitable for large-scale production; the activated carbon in the present invention has the advantages of high specific surface area and high mesopore ratio. The alkali activation treatment increases the micropores in the porous carbon, improves the specific surface area, enhances the adsorption capacity for impurities in the preparation process of tris(hydroxymethyl)aminomethane, further reduces the content of various impurities, and the product content purity reaches more than 99.9%. Detailed Embodiment

[0011] The technical solutions of the present invention will be described in detail below with reference to the embodiments, but the protection scope is not limited thereto. Embodiment

[0012] A method for preparing tris(hydroxymethyl)aminomethane includes the following steps: S1. Add 150 g of tris(hydroxymethyl)nitromethane, 600 g of methanol, 15 g of dichloromethane, and 15 g of Raney nickel into the reaction kettle, displace with nitrogen and ammonia for 4-6 times, start the stirrer, and control the reaction temperature in the reaction kettle to be 28-32 °C and the pressure to be 1.6-2.2 MPa; S2. Introduce hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 58-60 °C, adjust the pressure to 2.2-2.6 MPa, after reacting for 2-3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; The preparation method of the activated carbon includes: mixing an organic solid material, phosphoric acid and water for primary carbonization treatment, where the temperature of the primary carbonization treatment is 160 - 180 °C and the time is 36 - 45 h; after the primary carbonization treatment, conducting 1 - 3 times of secondary carbonization treatment, where the temperature of the subsequent secondary carbonization treatment is 500 - 560 °C and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C and the time is 45 - 60 min. After mixing the finally obtained pre-mixture with an alkaline activator, conducting alkali activation treatment to obtain the activated carbon; The organic solid material includes wood chips, lignite and crop residues; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into a refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane. Example

[0013] A preparation method of tris(hydroxymethyl)aminomethane includes the following steps S1. Add 150 g of tris(hydroxymethyl)nitromethane, 600 g of methanol, 15 g of dichloromethane and 15 g of Raney nickel into a reaction kettle, displace with nitrogen and ammonia for 4 - 6 times, start the stirrer, control the reaction temperature in the reaction kettle to be 28 - 32 °C and the pressure to be 1.6 - 2.2 MPa; S2. Introduce hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 60 °C, adjust the pressure to 2.5 MPa, after reacting for 3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; The preparation method of the activated carbon includes: mixing an organic solid material, phosphoric acid and water for primary carbonization treatment, where the temperature of the primary carbonization treatment is 160 - 180 °C and the time is 36 - 45 h; after the primary carbonization treatment, conducting 1 - 3 times of secondary carbonization treatment, where the temperature of the subsequent secondary carbonization treatment is 500 - 560 °C and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C and the time is 45 - 60 min. After mixing the finally obtained pre-mixture with an alkaline activator, conducting alkali activation treatment to obtain the activated carbon; The organic solid material includes wood chips, lignite and crop residues; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into a refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane. Example

[0014] A preparation method of tris(hydroxymethyl)aminomethane includes the following steps S1. Add 150 g of trimethylolnitromethane, 600 g of methanol, 15 g of dichloromethane and 15 g of Raney nickel into the reaction kettle, then add water. The molar ratio of water to methanol is 1:6. Replace with nitrogen and ammonia for 4 - 6 times. Start the stirrer and control the reaction temperature in the reaction kettle to be 28 - 32 °C and the pressure to be 1.6 - 2.2 MPa; S2. Introduce hydrogen into the reaction kettle in step S1. Slowly raise the reaction temperature to 60 °C and adjust the pressure to 2.5 MPa. After reacting for 3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; The preparation method of the activated carbon includes: mixing organic solid materials, phosphoric acid and water for primary carbonization treatment. The temperature of the primary carbonization treatment is 160 - 180 °C and the time is 36 - 45 h; after the primary carbonization treatment, perform 1 - 3 times of secondary carbonization treatment. The temperature of the subsequent secondary carbonization treatment is 500 - 560 °C and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C and the time is 45 - 60 min. After mixing the finally obtained pre - mixture with an alkaline activator, perform alkali activation treatment to obtain the activated carbon; The organic solid materials include wood chips, lignite and crop residues; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into the refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane.

[0015] Comparative Example 1: A preparation method of tris(hydroxymethyl)aminomethane includes the following steps, S1. Add 150 g of trimethylolnitromethane and 600 g of methanol into the reaction kettle, replace with nitrogen and ammonia for 4 - 6 times, start the stirrer, and control the reaction temperature in the reaction kettle to be 28 - 32 °C and the pressure to be 1.6 - 2.2 MPa; S2. Introduce hydrogen into the reaction kettle in step S1. Slowly raise the reaction temperature to 58 - 60 °C and adjust the pressure to 2.2 - 2.6 MPa. After reacting for 2 - 3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; The preparation method of the activated carbon described above includes: mixing an organic solid material, phosphoric acid and water for primary carbonization treatment, where the temperature of the primary carbonization treatment is 160 - 180 °C and the time is 36 - 45 h; after the primary carbonization treatment, conducting 1 - 3 times of secondary carbonization treatment, where the temperature of the subsequent secondary carbonization treatment is 500 - 560 °C and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C and the time is 45 - 60 min. After mixing the finally obtained premix with an alkaline activator, conducting alkali activation treatment to obtain the activated carbon; The organic solid material described above includes wood chips, lignite and crop residues; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into a refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane.

[0016] Comparative Example 2: A preparation method of tris(hydroxymethyl)aminomethane includes the following steps, S1. Add 150 g of tris(hydroxymethyl)nitromethane, 600 g of methanol, 15 g of dichloromethane and 15 g of Raney nickel into a reaction kettle, displace with nitrogen and ammonia for 4 - 6 times, start the stirrer, and control the reaction temperature in the reaction kettle to be 28 - 32 °C and the pressure to be 1.6 - 2.2 MPa; S2. Introduce hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 58 - 60 °C, adjust the pressure to 2.2 - 2.6 MPa, after reacting for 2 - 3 hours, add ordinary activated carbon on the market, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into a refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane.

[0017] Comparative Example 3: A preparation method of tris(hydroxymethyl)aminomethane includes the following steps, S1. Add 100 - 150 g of tris(hydroxymethyl)nitromethane, 650 - 700 g of methanol, 20 - 30 g of dichloromethane and 20 - 30 g of Raney nickel into a reaction kettle, displace with nitrogen and ammonia for 4 - 6 times, start the stirrer, and control the reaction temperature in the reaction kettle to be 28 - 32 °C and the pressure to be 1.6 - 2.2 MPa; S2. Hydrogen is introduced into the reactor in step S1, the reaction temperature is slowly raised to 58 - 60 °C, the pressure is adjusted to 2.2 - 2.6 MPa. After reacting for 2 - 3 hours, activated carbon is added, the temperature is lowered to 0 °C - 2 °C, crystals are precipitated, and crude tris(hydroxymethyl)aminomethane is obtained by filtration; The preparation method of the activated carbon described above includes: mixing organic solid materials, phosphoric acid and water for primary carbonization treatment, the temperature of the primary carbonization treatment is 160 - 180 °C, and the time is 36 - 45 h; after the primary carbonization treatment, 1 - 3 times of re-carbonization treatment are carried out, the temperature of the subsequent re-carbonization treatment is 500 - 560 °C, and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C, and the time is 45 - 60 min. After the finally obtained premix is mixed with an alkaline activator, alkali activation treatment is carried out to obtain the activated carbon; The organic solid materials include wood chips, lignite and crop residues; S3. The crude tris(hydroxymethyl)aminomethane obtained in step S2 is added to a refining kettle, methanol and water are added again, the temperature is raised to 60 °C - 80 °C, stirred for 1 - 2 hours, cooled to precipitate crystals, filtered, and dried to obtain the finished product of tris(hydroxymethyl)aminomethane.

[0018] Experimental Example The yields and purities of the product tris(hydroxymethyl)aminomethane generated in the above Examples 1 - 3 and Comparative Examples 1 - 3 are shown in Table 1 as follows:

[0019] Table 1 From the results in Table 1, it can be seen that the product yield of the tris(hydroxymethyl)aminomethane prepared by the present invention is as high as over 95.6%, and the product purity is as high as over 99.2%; in Examples 2 and 3, after introducing hydrogen into the reactor, by adjusting the reaction temperature, pressure and reaction time and by adding water to the reaction raw materials and maintaining the molar ratio between water and methanol, the product yield can be significantly improved; in addition, combined with Comparative Examples 1 - 3, when Raney nickel is not added to the reaction raw materials or the mass parts of tris(hydroxymethyl)nitromethane, methanol, dichloromethane and Raney nickel are not added according to 10:40:1:1, the product yield decreases significantly; combined with Comparative Example 2, the activated carbon added in the present invention has a significant impact on the improvement of the product purity.

[0020] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the purpose and scope of the present technical solution, and they should all be covered within the scope of the claims of the present invention.

Claims

1. A preparation method of tris(hydroxymethyl)aminomethane, characterized in that, It includes the following steps: S1. Add tris(hydroxymethyl)nitromethane, methanol, dichloromethane and Raney nickel into the reaction kettle, displace with nitrogen and ammonia for 4 - 6 times, start the stirrer, control the reaction temperature in the reaction kettle at 28 - 32 °C and the pressure at 1.6 - 2.2 MPa. Among them, the mass fraction ratio of tris(hydroxymethyl)nitromethane, methanol, dichloromethane and Raney nickel is 10:40:1:1; S2. Pass hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 58 - 60 °C, adjust the pressure to 2.2 - 2.6 MPa. After reacting for 2 - 3 hours, add activated carbon, cool down to 0 °C - 2 °C, precipitate crystals, and filter to obtain the crude product of tris(hydroxymethyl)aminomethane; S3. Add the crude product of tris(hydroxymethyl)aminomethane obtained in step S2 into the refining kettle, then add methanol and water, heat up to 60 °C - 80 °C, stir for 1 - 2 hours, cool down to precipitate crystals, filter, and dry to obtain the finished product of tris(hydroxymethyl)aminomethane.

2. The preparation method of tris(hydroxymethyl)aminomethane according to claim 1, wherein Add water to step S1, and the molar ratio of water to methanol is 1:

6.

3. The preparation method of tris(hydroxymethyl)aminomethane according to claim 1, characterized in that, The preparation method of the activated carbon in step S2 includes: mixing organic solid materials, phosphoric acid and water for primary carbonization treatment, the temperature of the primary carbonization treatment is 160 - 180 °C, and the time is 36 - 45 h; after the primary carbonization treatment, carry out 1 - 3 times of secondary carbonization treatment. After mixing the finally obtained premix with an alkaline activator, carry out alkali activation treatment to obtain the activated carbon.

4. The preparation method of tris(hydroxymethyl)aminomethane according to claim 4, characterized in that, The temperature of the secondary carbonization treatment is 500 - 560 °C, and the time is 1 - 2 h; the temperature of the alkali activation treatment is 750 - 800 °C, and the time is 45 - 60 min.

5. The preparation method of tris (hydroxymethyl) aminomethane according to claim 4, characterized in that, The organic solid materials include wood chips, lignite and crop residues.

6. The preparation method of tris (hydroxymethyl) aminomethane according to claim 1, characterized in that, Pass hydrogen into the reaction kettle in step S1, slowly raise the reaction temperature to 60 °C, adjust the pressure to 2.5 MPa, and react for 3 hours.

Images