Production method of sulfadiazine sodium

Abstract

The invention discloses a production method of sulfadiazine sodium, and belongs to the technical field of sulfadiazine sodium preparation, sulfadiazine and a sodium hydroxide solution are used as raw materials, modified charcoal supported sodium tert-butoxide is used as a catalyst, sulfadiazine reacts with the sodium hydroxide solution after high-temperature steam pretreatment, the reaction temperature is controlled to be 35.6 DEG C, and the reaction time is controlled to be 2.0 h; and filtering, adding a composite additive and water for injection, and uniformly mixing to obtain the composite injection type sulfadiazine sodium, detecting that the yield of the sulfadiazine sodium in the product is greater than or equal to 97.6%, and the purity of the sulfadiazine sodium is greater than or equal to 97.1%. According to the method, the modified charcoal is adopted to load the sodium tert-butoxide catalyst, separation can be realized by filtering after the reaction is finished, and the requirements of no influence on the product, convenience in subsequent recovery, improvement of the product yield and purity and the like can be met.

Description

Technical Field

[0001] The invention relates to the technical field of sulfadiazine sodium preparation, and in particular to a production method of sulfadiazine sodium. Background Art

[0002] Sulfadiazine sodium is a medium-acting sulfonamide antibiotic that has antibacterial effects on many Gram-positive and Gram-negative bacteria. The traditional preparation process of sulfadiazine sodium is to react sulfadiazine with sodium hydroxide solution in a 1:1 molar ratio to generate sulfadiazine sodium.

[0003] Generally, sulfadiazine adopts crystalline powder, and is blended by dispersing and dissolving in sodium hydroxide solution, and the chemical reaction temperature should not be too high. In order to improve the reaction efficiency, a reaction catalyst can be added thereto. However, the reaction catalyst preferably can simultaneously meet the requirements of not affecting the product, facilitating subsequent recovery, and improving the product yield and purity. Based on this, the present invention designs a production method of sulfadiazine sodium to solve the above problems. Summary of the invention

[0004] In view of the above-mentioned shortcomings of the prior art, the present invention provides a method for producing sulfadiazine sodium.

[0005] To achieve the above objectives, the present invention is implemented through the following technical solutions: A production method of sulfadiazine sodium comprises the following steps: using sulfadiazine and sodium hydroxide solution as raw materials, using modified biochar loaded with sodium tert-butoxide as a catalyst, reacting sulfadiazine with the sodium hydroxide solution after high-temperature steam pretreatment, controlling the reaction temperature at 35.6-45.1°C, and controlling the reaction time at 1.3-2.0h; adding composite additives and injection water after filtration, and mixing evenly to obtain a composite injection form of sulfadiazine sodium.

[0006] Furthermore, the sodium hydroxide solution uses a sodium hydroxide solution with a mass fraction of 18-22%.

[0007] Furthermore, the molar ratio of sulfadiazine to sodium hydroxide solution is 0.9-1:1-1.2.

[0008] Furthermore, the molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.13-0.21.

[0009] Furthermore, the sulfadiazine includes a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 125-130° C. steam and 2.2-3.1 MPa conditions, and stirred for 15-20 minutes.

[0010] Furthermore, the modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 15.4-20.1:1-1.3:4.9-7.8 and then grinding.

[0011] Furthermore, the preparation method of the modified biochar loaded with sodium tert-butoxide is: mixing the biochar and sodium carbonate, calcining and activating the mixture at 450-500°C, then taking out, cooling and grinding the mixture to 50-70 μm, adding sodium tert-butoxide, calcining and activating the mixture at 145-155°C, then taking out, cooling and grinding the mixture to 10-20 μm.

[0012] Furthermore, the mass ratio of sulfadiazine to the composite additive is 86-100:1.

[0013] Furthermore, the composite additive includes ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.5-0.8:1.

[0014] In order to better achieve the purpose of the present invention, the present invention also provides sulfadiazine sodium prepared by the production method.

[0015] Compared with the prior art, the present invention has the following beneficial effects: the present invention uses sulfadiazine and sodium hydroxide solution as raw materials, uses modified biochar loaded sodium tert-butoxide as a catalyst, reacts sulfadiazine with sodium hydroxide solution after high-temperature steam pretreatment, controls the reaction temperature at 35.6°C, and controls the reaction time at 2.0h; after filtration, adds composite additives and injection water, and mixes evenly to obtain a composite injection form of sulfadiazine sodium, and the yield of sulfadiazine sodium in the detected product is ≥97.6%, and the purity is ≥97.1%. The present invention uses modified biochar loaded sodium tert-butoxide catalyst, and can be separated by filtration after the reaction is completed, which can simultaneously meet the requirements of not affecting the product, facilitating subsequent recovery, and improving the product yield and purity. DETAILED DESCRIPTION

[0016] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0017] Embodiment 1: In some embodiments, a method for producing sodium sulfadiazine is provided, wherein sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar-loaded sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and reacted with sodium hydroxide solution, the reaction temperature is controlled at 35.6°C, and the reaction time is controlled at 2.0h; after filtering, the yield and purity of sodium sulfadiazine are detected, and then a composite additive and water for injection are added, and after mixing evenly, a composite injection form of sodium sulfadiazine is obtained; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 18%; The molar ratio of sulfadiazine to sodium hydroxide solution is 0.9:1.2; The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.13; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 125°C steam and 3.1MPa conditions, and stirred for 15 minutes; The modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 15.4:1.3:4.9 and then grinding; The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, and the mixture is calcined and activated at 450°C, then the mixture is taken out, cooled, and ground to 70 μm, and sodium tert-butoxide is added, the mixture is calcined and activated at 145°C, and then the mixture is taken out, cooled, and ground to 20 μm; The mass ratio of sulfadiazine to the composite additive is 86:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.5:1.

[0018] The reaction catalyst prepared by the present invention can simultaneously meet the requirements of not affecting the product and being easy to recover later.

[0019] The yield of sulfadiazine sodium in the detected product was 98.5% and the purity was 97.1%.

[0020] Embodiment 2: In some embodiments, a method for producing sodium sulfadiazine is provided, wherein sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar-loaded sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and reacted with the sodium hydroxide solution, the reaction temperature is controlled at 45.1°C, and the reaction time is controlled at 1.3h; the yield and purity of sodium sulfadiazine are detected after filtration, and then a composite additive and water for injection are added, and the mixture is mixed evenly to obtain a composite injection form of sodium sulfadiazine; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 22%; The molar ratio of sulfadiazine to sodium hydroxide solution is 1:1; The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.21; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 130° C. steam and 2.2 MPa conditions, and stirred for 20 minutes; The modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 20.1:1:7.8 and then grinding; The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, and the mixture is calcined and activated at 500°C, and then the mixture is taken out, cooled, and ground to 50 μm, and then sodium tert-butoxide is added, and the mixture is calcined and activated at 155°C, and then the mixture is taken out, cooled, and ground to 10 μm; The mass ratio of sulfadiazine to the composite additive is 100:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.8:1.

[0021] The yield of sulfadiazine sodium in the detected product was 97.6% and the purity was 98.3%.

[0022] Embodiment 3: In some embodiments, a method for producing sodium sulfadiazine is provided, wherein sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar-loaded sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and reacted with the sodium hydroxide solution, the reaction temperature is controlled at 36°C, and the reaction time is controlled at 1.5 hours; after filtering, the yield and purity of sodium sulfadiazine are detected, and then a composite additive and water for injection are added, and after mixing evenly, a composite injection form of sodium sulfadiazine is obtained; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 19%; The molar ratio of sulfadiazine to sodium hydroxide solution is 1:1.1; The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.15; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 127°C steam and 2.5MPa conditions, and stirred for 17 minutes; The modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 17:1.2:5 and then grinding. The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, calcined and activated at 470°C, then taken out, cooled and ground to 60 μm, then sodium tert-butoxide is added, calcined and activated at 148°C, then taken out, cooled and ground to 15 μm; The mass ratio of sulfadiazine to the composite additive is 90:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.6:1.

[0023] The yield of sulfadiazine sodium in the detected product was 98.8% and the purity was 98.4%.

[0024] Example 4: In some embodiments, a method for producing sodium sulfadiazine is provided, wherein sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar-loaded sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and reacted with the sodium hydroxide solution, the reaction temperature is controlled at 38.1°C, and the reaction time is controlled at 1.5h; the yield and purity of sodium sulfadiazine are detected after filtration, and then a composite additive and water for injection are added, and the mixture is mixed evenly to obtain a composite injection form of sodium sulfadiazine; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 20%; The molar ratio of sulfadiazine to sodium hydroxide solution is 0.9:1; The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.2; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 129°C steam and 3MPa conditions, and stirred for 18 minutes; The modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 20:1.2:6.5 and then grinding. The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, and the mixture is calcined and activated at 490° C., then the mixture is taken out, cooled, and ground to 65 μm, and sodium tert-butoxide is added, and the mixture is calcined and activated at 150° C., and then the mixture is taken out, cooled, and ground to 17 μm; The mass ratio of sulfadiazine to the composite additive is 92:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.7:1.

[0025] Example 5: In some embodiments, a method for producing sodium sulfadiazine is provided, wherein sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar-loaded sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and reacted with the sodium hydroxide solution, the reaction temperature is controlled at 42°C, and the reaction time is controlled at 1.9 hours; after filtering, the yield and purity of sodium sulfadiazine are detected, and then a composite additive and water for injection are added, and after mixing evenly, a composite injection form of sodium sulfadiazine is obtained; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 21%; The molar ratio of sulfadiazine to sodium hydroxide solution is 0.9:1.2; The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.19; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 128°C steam and 2.7MPa conditions, and stirred for 19 minutes; The modified biochar loaded with sodium tert-butoxide is prepared by calcining and activating biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 18.8:1.2:7 and then grinding. The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, calcined and activated at 495°C, then taken out, cooled and ground to 65 μm, then sodium tert-butoxide is added, calcined and activated at 148°C, then taken out, cooled and ground to 16 μm; The mass ratio of sulfadiazine to the composite additive is 93:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.7:1.

[0026] Comparative Example 1: The difference from Example 3 is that the sodium tert-butoxide loaded on the modified biochar is replaced by trifluoromethanesulfonic acid.

[0027] A method for producing sulfadiazine sodium, comprising: using sulfadiazine and sodium hydroxide solution as raw materials, using trifluoromethanesulfonic acid as a catalyst, reacting sulfadiazine with the sodium hydroxide solution after high-temperature steam pretreatment, controlling the reaction temperature at 36°C, and controlling the reaction time at 1.5 hours; detecting the yield and purity of sulfadiazine sodium after filtration, then adding a composite additive and injection water, and mixing evenly to obtain a composite injection form of sulfadiazine sodium; Wherein, the sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 19%; The molar ratio of sulfadiazine to sodium hydroxide solution is 1:1.1; The molar ratio of sulfadiazine to trifluoromethanesulfonic acid is 1:0.15; The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with trifluoromethanesulfonic acid, placed under 127°C steam and 2.5MPa conditions, and stirred for 17 minutes; The mass ratio of sulfadiazine to the composite additive is 90:1; The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.6:1.

[0028] The yield of sulfadiazine sodium in the detected product was 95.7% and the purity was 96.7%.

[0029] It can be seen that the present invention uses modified biochar to load sodium tert-butoxide catalyst, which can be separated by filtration after the reaction is completed, and can simultaneously meet the requirements of not affecting the product, facilitating subsequent recovery, and improving product yield and purity.

[0030] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for producing sulfadiazine sodium, characterized in that: Sulfadiazine and sodium hydroxide solution are used as raw materials, modified biochar loaded with sodium tert-butoxide is used as a catalyst, sulfadiazine is pretreated with high-temperature steam and then reacted with sodium hydroxide solution, the reaction temperature is controlled at 35.6-45.1°C, and the reaction time is controlled at 1.3-2.0h; after filtration, composite additives and water for injection are added, and the mixture is mixed evenly to obtain a composite injection form of sulfadiazine sodium.

2. The method for producing sulfadiazine sodium according to claim 1, characterized in that: in, The sodium hydroxide solution adopts a sodium hydroxide solution with a mass fraction of 18-22%.

3. The method for producing sulfadiazine sodium according to claim 1, characterized in that: The molar ratio of the sulfadiazine to the sodium hydroxide solution is 0.9-1:1-1.

2.

4. The method for producing sulfadiazine sodium according to claim 1, characterized in that: The molar ratio of sulfadiazine to modified biochar loaded sodium tert-butoxide is 1:0.13-0.

21.

5. The method for producing sulfadiazine sodium according to claim 1, characterized in that: The sulfadiazine comprises a pretreatment process: sulfadiazine is mixed with modified biochar loaded with sodium tert-butoxide, placed under 125-130° C. steam and 2.2-3.1 MPa conditions, and stirred for 15-20 minutes.

6. The method for producing sulfadiazine sodium according to claim 5, characterized in that: The modified biochar loaded with sodium tert-butoxide is prepared by calcining, activating and grinding biochar, sodium carbonate and sodium tert-butoxide in a mass ratio of 15.4-20.1:1-1.3:4.9-7.

8.

7. The method for producing sulfadiazine sodium according to claim 6, characterized in that: The preparation method of the modified biochar loaded with sodium tert-butoxide is as follows: biochar and sodium carbonate are mixed, and the mixture is subjected to calcination and activation treatment at 450-500° C., and then the mixture is taken out, cooled, and ground to 50-70 μm, and then sodium tert-butoxide is added, and the mixture is subjected to calcination and activation treatment at 145-155° C., and then the mixture is taken out, cooled, and ground to 10-20 μm.

8. The method for producing sulfadiazine sodium according to claim 7, characterized in that: The mass ratio of the sulfadiazine to the composite additive is 86-100:

1.

9. The method for producing sulfadiazine sodium according to claim 1, characterized in that: The composite additive comprises ursolic acid and vitamin E, and the mass ratio of ursolic acid to vitamin E is 0.5-0.8:

1.

10. Sulfadiazine sodium prepared by the production method according to any one of claims 1 to 9.