CN111410635A - Preparation process of sulfadoxine - Google Patents
Preparation process of sulfadoxine Download PDFInfo
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- CN111410635A CN111410635A CN202010391228.3A CN202010391228A CN111410635A CN 111410635 A CN111410635 A CN 111410635A CN 202010391228 A CN202010391228 A CN 202010391228A CN 111410635 A CN111410635 A CN 111410635A
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- PJSFRIWCGOHTNF-UHFFFAOYSA-N Sulphormetoxin Chemical compound COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC PJSFRIWCGOHTNF-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 229960004673 sulfadoxine Drugs 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 27
- 238000003756 stirring Methods 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 12
- ICPWFHKNYYRBSZ-UHFFFAOYSA-M 2-methoxypropanoate Chemical compound COC(C)C([O-])=O ICPWFHKNYYRBSZ-UHFFFAOYSA-M 0.000 claims abstract description 5
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 34
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 238000010438 heat treatment Methods 0.000 claims description 16
- 238000001556 precipitation Methods 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 230000001276 controlling effect Effects 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 238000004042 decolorization Methods 0.000 claims description 8
- 238000007599 discharging Methods 0.000 claims description 8
- 239000012065 filter cake Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 230000006324 decarbonylation Effects 0.000 claims description 4
- 238000006606 decarbonylation reaction Methods 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000003825 pressing Methods 0.000 claims description 4
- 238000011085 pressure filtration Methods 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 229960000583 acetic acid Drugs 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000011259 mixed solution Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- 238000007726 management method Methods 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XSFRVYMZSANDAB-UHFFFAOYSA-N 4-amino-n-(6-chloro-5-methoxypyrimidin-4-yl)benzenesulfonamide Chemical compound COC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1 XSFRVYMZSANDAB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000006198 methoxylation reaction Methods 0.000 description 2
- 241000588986 Alcaligenes Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229940007046 shigella dysenteriae Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation process of sulfadoxine, which comprises the following specific steps: the method comprises the following steps: technical personnel are familiar with a special scheme of a sulfadoxine preparation process in detail, draw doubts and solve the problems, and finally draw a technical general supervision and approval for the agreed special scheme; step two: adding a methanol solution into a reaction kettle with a stirrer, adding sodium hydroxide, starting stirring, adding 4- (p-aminobenzene sulfonamide) -5-methoxy-6-chloropyrimidine for reflux reaction, controlling the reflux reaction temperature and the reflux reaction time, and recovering methanol until the methanol is dried after the reaction is finished to obtain sodium methoxide; step three: 184g of 27-28% sodium methoxide is put into a reaction bottle, methanol is evaporated to dryness, and then a mixed solution of 83g of methyl methoxyacetate and 142g of diethyl oxalate is put into the reaction bottle, and the temperature is naturally raised. The preparation process of the sulfadoxine is stable and reliable, simple in equipment, low in manufacturing cost, convenient to operate, strong in practicability and suitable for wide popularization and use.
Description
Technical Field
The invention belongs to the technical field of medical production, and particularly relates to a preparation process of sulfadoxine.
Background
Sulfadoxine has antibacterial effect on Staphylococcus, pneumococcus, meningococcus, Escherichia coli, Proteus, Shigella dysenteriae, Bacillus coli, Alcaligenes, Salmonella, etc., and the minimum antibacterial concentration is 16-32 microgram/ml. The bacteriostatic action on general bacteria is weaker than that of other sulfa drugs, and 50 percent of strains are inhibited when the drug concentration is 12.5 micrograms/ml on escherichia coli, escherichia coli and staphylococcus aureus box dysentery bacillus. SDM' was also reported to be effective against malaria, leprosy, tuberculosis abroad. The existing preparation process of sulfadoxine has the disadvantages of complicated steps, easy error, convenient operation, high cost, greatly reduced yield of sulfadoxine and poor practicability.
Disclosure of Invention
The invention aims to provide a preparation process of sulfadoxine, which aims to solve the problems of complicated steps, easy error, convenient operation, high cost, greatly weakened sulfadoxine yield and poor practicability of the existing preparation process of sulfadoxine in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme: a preparation process of sulfadoxine comprises the following specific preparation process steps:
the method comprises the following steps: technical personnel are familiar with a special scheme of a sulfadoxine preparation process in detail, draw doubts and solve the problems, and finally draw a technical general supervision and approval for the agreed special scheme;
step two: adding a methanol solution into a reaction kettle with a stirrer, adding sodium hydroxide, starting stirring, adding 4- (p-aminobenzene sulfonamide) -5-methoxy-6-chloropyrimidine for reflux reaction, controlling the reflux reaction temperature and the reflux reaction time, and recovering methanol until the methanol is dried after the reaction is finished to obtain sodium methoxide;
step three: putting 184g of 27-28% sodium methoxide into a reaction bottle, evaporating the methanol to dryness, putting 83g of methyl methoxyacetate and 142g of diethyl oxalate into the reaction bottle, and naturally raising the temperature;
step four, adding 200ml of trichloroethylene, adding hydrochloric acid to adjust the pH to be =2, standing, separating a trichloroethylene layer, extracting a water layer by trichloroethylene 7 × 50, combining trichloroethylene extract, recovering trichloroethylene, decarbonylating for 4 hours at the temperature of 180 ℃ and 210 ℃/360mmHg, heating sodium methoxide to 60-65 ℃, and dripping 58.6g of kresoxim and adding 250ml of trichloroethylene;
step five: adding water, continuously recovering methanol, pressing the feed liquid into a decoloring pot, adjusting the pH value with acid liquor, adding water and a decoloring agent into the feed liquid, and keeping the temperature and decoloring; filtering the decolored mixture by a filter press to a precipitation pot for precipitation, controlling the precipitation temperature, regulating the pH value by using an acid solution after the precipitation is finished, then centrifugally dewatering, washing by using water, spin-drying and discharging to obtain a sulfadoxine crude product;
step six: adding water into a dissolving pot, adding a sulfadoxine crude product under heating and stirring, adding calcium to fully dissolve the sulfadoxine crude product to obtain a solution to be decolorized, adding a decolorizing agent for decolorization, controlling the decolorizing temperature and the decolorizing time, performing pressure filtration by a filter press to the crystallizing pot after decolorization, and adding an acid solution dropwise to adjust the pH value;
step seven: and centrifugally dewatering after the dropwise adding is finished to obtain a filter cake, washing the filter cake with water until a liquid outlet is clarified, centrifugally drying, discharging and drying to obtain a sulfadoxine finished product.
Furthermore, in the step one, technical management personnel carry out technical delivery to the staff after approval of the technical scheme, and both parties sign, file and store the technical scheme.
Further, in the third step, the temperature is controlled to be 45-55 ℃ for reaction for 4 hours, the temperature is cooled to be 25-30 ℃ for reaction for 15 hours, and then the temperature is controlled to be below 35 ℃.
Further, after decarbonylation is carried out for 4 hours in the fourth step, the Kjeldahl substance is distilled under reduced pressure to obtain 125.5g,90-120 ℃/750mmHg or 145 ℃/720 and 750mmHg at 120-; the yield thereof was found to be 89%.
Further, the heating is carried out to 80-85 ℃ for 3 hours in the sixth step, and the stirring is carried out while heating, wherein the stirring speed is 120-140 r/min.
Further, the pH value is adjusted to 9.0-12 by using an acid solution in the fifth step, wherein the pH value is adjusted to 20-40% by mass of glacial acetic acid solution.
Compared with the prior art, the invention has the beneficial effects that:
(1) although the method has more steps, the used raw materials are easily obtained, the process of each step is mature, the equipment requirement is not high, and the production is easy to carry out. One of the advantages of the technical scheme provided by the invention is that solid sodium hydroxide is used in the methoxylation reaction, so that the 4- (p-aminobenzenesulfonamido) -5-methoxy-6-chloropyrimidine can react completely, and the yield of sulfadoxine is greatly improved; secondly, solid sodium hydroxide is used, so that the quality of the final product is stable.
(2) Adding 200ml of trichloroethylene, adding hydrochloric acid to adjust the pH value to be =2, standing, separating a trichloroethylene layer, extracting a water layer by using trichloroethylene 7 × 50, combining trichloroethylene extract, recovering trichloroethylene, decarbonylating for 4 hours at the temperature of 180 ℃ and the temperature of 360mmHg, and performing cyclization, chlorination, condensation and etherification, wherein the production process in each step is tightly jointed, the stability is good, and manpower and material resources are saved.
(6) The preparation process of the sulfadoxine is stable and reliable, simple in equipment, low in manufacturing cost, convenient to operate, strong in practicability and suitable for wide popularization and use.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation process of sulfadoxine comprises the following specific preparation process steps:
the method comprises the following steps: technical personnel are familiar with a special scheme of a sulfadoxine preparation process in detail, draw doubts and solve the problems, and finally draw a technical general supervision and approval for the agreed special scheme;
step two: adding a methanol solution into a reaction kettle with a stirrer, adding sodium hydroxide, starting stirring, adding 4- (p-aminobenzene sulfonamide) -5-methoxy-6-chloropyrimidine for reflux reaction, controlling the reflux reaction temperature and the reflux reaction time, and recovering methanol until the methanol is dried after the reaction is finished to obtain sodium methoxide;
step three: putting 184g of 27-28% sodium methoxide into a reaction bottle, evaporating the methanol to dryness, putting 83g of methyl methoxyacetate and 142g of diethyl oxalate into the reaction bottle, and naturally raising the temperature;
step four, adding 200ml of trichloroethylene, adding hydrochloric acid to adjust the pH to be =2, standing, separating a trichloroethylene layer, extracting a water layer by trichloroethylene 7 × 50, combining trichloroethylene extract, recovering trichloroethylene, decarbonylating for 4 hours at the temperature of 180 ℃ and 210 ℃/360mmHg, heating sodium methoxide to 60-65 ℃, and dripping 58.6g of kresoxim and adding 250ml of trichloroethylene;
step five: adding water, continuously recovering methanol, pressing the feed liquid into a decoloring pot, adjusting the pH value with acid liquor, adding water and a decoloring agent into the feed liquid, and keeping the temperature and decoloring; filtering the decolored mixture by a filter press to a precipitation pot for precipitation, controlling the precipitation temperature, regulating the pH value by using an acid solution after the precipitation is finished, then centrifugally dewatering, washing by using water, spin-drying and discharging to obtain a sulfadoxine crude product;
step six: adding water into a dissolving pot, adding a sulfadoxine crude product under heating and stirring, adding calcium to fully dissolve the sulfadoxine crude product to obtain a solution to be decolorized, adding a decolorizing agent for decolorization, controlling the decolorizing temperature and the decolorizing time, performing pressure filtration by a filter press to the crystallizing pot after decolorization, and adding an acid solution dropwise to adjust the pH value;
step seven: and centrifugally dewatering after the dropwise adding is finished to obtain a filter cake, washing the filter cake with water until a liquid outlet is clarified, centrifugally drying, discharging and drying to obtain a sulfadoxine finished product.
And in the step one, the technical management personnel carry out technical interaction on the technical scheme after approval to the working personnel, sign the technical scheme and store the technical scheme by both the technical management personnel and the working personnel in a filing manner.
Wherein, the temperature in the third step is controlled to be 45-55 ℃ for reaction for 4 hours, the temperature is cooled to be 25-30 ℃ for reaction for 15 hours, and then the temperature is controlled to be below 35 ℃.
Wherein, after decarbonylation is carried out for 4 hours in the fourth step, the Kjeldahl substance is distilled under reduced pressure to obtain 125.5g,90-120 ℃/750mmHg or 145 ℃/720 and 750mmHg at 120-; the yield thereof was found to be 89%.
Wherein, the heating is carried out to 80-85 ℃ for 3 hours in the sixth step, and the stirring is carried out while heating, and the stirring speed is 120-140 r/min.
Wherein, the pH value is adjusted to 9.0-12 by using glacial acetic acid solution with the mass percentage concentration of 20-40% in the fifth step.
Example 2
A preparation process of sulfadoxine comprises the following specific preparation process steps:
the method comprises the following steps: technical personnel are familiar with a special scheme of a sulfadoxine preparation process in detail, draw doubts and solve the problems, and finally draw a technical general supervision and approval for the agreed special scheme;
step two: adding a methanol solution into a reaction kettle with a stirrer, adding sodium hydroxide, starting stirring, adding 4- (p-aminobenzene sulfonamide) -5-methoxy-6-chloropyrimidine for reflux reaction, controlling the reflux reaction temperature and the reflux reaction time, and recovering methanol until the methanol is dried after the reaction is finished to obtain sodium methoxide;
step three: putting 184g of 27-28% sodium methoxide into a reaction bottle, evaporating the methanol to dryness, putting 83g of methyl methoxyacetate and 142g of diethyl oxalate into the reaction bottle, and naturally raising the temperature;
step four, adding 200ml of trichloroethylene, adding hydrochloric acid to adjust the pH to be =2, standing, separating a trichloroethylene layer, extracting a water layer by trichloroethylene 7 × 50, combining trichloroethylene extract, recovering trichloroethylene, decarbonylating for 4 hours at the temperature of 180 ℃ and 210 ℃/360mmHg, heating sodium methoxide to 60-65 ℃, and dripping 58.6g of kresoxim and adding 250ml of trichloroethylene;
step five: adding water, continuously recovering methanol, pressing the feed liquid into a decoloring pot, adjusting the pH value with acid liquor, adding water and a decoloring agent into the feed liquid, and keeping the temperature and decoloring; filtering the decolored mixture by a filter press to a precipitation pot for precipitation, controlling the precipitation temperature, regulating the pH value by using an acid solution after the precipitation is finished, then centrifugally dewatering, washing by using water, spin-drying and discharging to obtain a sulfadoxine crude product;
step six: adding water into a dissolving pot, adding a sulfadoxine crude product under heating and stirring, adding calcium to fully dissolve the sulfadoxine crude product to obtain a solution to be decolorized, adding a decolorizing agent for decolorization, controlling the decolorizing temperature and the decolorizing time, performing pressure filtration by a filter press to the crystallizing pot after decolorization, and adding an acid solution dropwise to adjust the pH value;
step seven: and centrifugally dewatering after the dropwise adding is finished to obtain a filter cake, washing the filter cake with water until a liquid outlet is clarified, centrifugally drying, discharging and drying to obtain a sulfadoxine finished product.
And in the step one, the technical management personnel carry out technical interaction on the technical scheme after approval to the working personnel, sign the technical scheme and store the technical scheme by both the technical management personnel and the working personnel in a filing manner.
Wherein, the temperature in the third step is controlled to be 45-55 ℃ for reaction for 4 hours, the temperature is cooled to be 25-30 ℃ for reaction for 15 hours, and then the temperature is controlled to be below 35 ℃.
Wherein, after decarbonylation is carried out for 4 hours in the fourth step, the Kjeldahl substance is distilled under reduced pressure to obtain 125.5g,90-120 ℃/750mmHg or 145 ℃/720 and 750mmHg at 120-; the yield thereof was found to be 89%.
Wherein, the heating is carried out to 80-85 ℃ for 3 hours in the sixth step, and the stirring is carried out while heating, and the stirring speed is 120-140 r/min.
Wherein, the pH value is adjusted to 9.0-12 by using sulfuric acid solution with the mass percentage concentration of 20-40% in the fifth step.
The invention has the advantages that solid sodium hydroxide is used in the methoxylation reaction, so that the 4- (p-aminobenzenesulfonamido) -5-methoxy-6-chloropyrimidine can completely react, the yield of the sulfadoxine is greatly improved, and secondly, solid sodium hydroxide is used, so that the quality of a final product is stable, 200ml of trichloroethylene is added, hydrochloric acid is added to regulate the pH value to be =2, the trichloroethylene layer is taken out after standing, trichloroethylene 7 × 50 is used, trichloroethylene is combined for extraction, after the trichloroethylene is recovered, the cyclic combination, chlorination, condensation and etherification are carried out at the temperature of 210 ℃/360mmHg for 4 hours, the production process in each step is compact, the stability is good, and the linked manpower and material resources are saved.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (6)
1. A preparation process of sulfadoxine is characterized by comprising the following specific preparation process steps:
the method comprises the following steps: technical personnel are familiar with a special scheme of a sulfadoxine preparation process in detail, draw doubts and solve the problems, and finally draw a technical general supervision and approval for the agreed special scheme;
step two: adding a methanol solution into a reaction kettle with a stirrer, adding sodium hydroxide, starting stirring, adding 4- (p-aminobenzene sulfonamide) -5-methoxy-6-chloropyrimidine for reflux reaction, controlling the reflux reaction temperature and the reflux reaction time, and recovering methanol until the methanol is dried after the reaction is finished to obtain sodium methoxide;
step three: putting 184g of 27-28% sodium methoxide into a reaction bottle, evaporating the methanol to dryness, putting 83g of methyl methoxyacetate and 142g of diethyl oxalate into the reaction bottle, and naturally raising the temperature;
step four, adding 200ml of trichloroethylene, adding hydrochloric acid to adjust the pH to be =2, standing, separating a trichloroethylene layer, extracting a water layer by trichloroethylene 7 × 50, combining trichloroethylene extract, recovering trichloroethylene, decarbonylating for 4 hours at the temperature of 180 ℃ and 210 ℃/360mmHg, heating sodium methoxide to 60-65 ℃, and dripping 58.6g of kresoxim and adding 250ml of trichloroethylene;
step five: adding water, continuously recovering methanol, pressing the feed liquid into a decoloring pot, adjusting the pH value with acid liquor, adding water and a decoloring agent into the feed liquid, and keeping the temperature and decoloring; filtering the decolored mixture by a filter press to a precipitation pot for precipitation, controlling the precipitation temperature, regulating the pH value by using an acid solution after the precipitation is finished, then centrifugally dewatering, washing by using water, spin-drying and discharging to obtain a sulfadoxine crude product;
step six: adding water into a dissolving pot, adding a sulfadoxine crude product under heating and stirring, adding calcium to fully dissolve the sulfadoxine crude product to obtain a solution to be decolorized, adding a decolorizing agent for decolorization, controlling the decolorizing temperature and the decolorizing time, performing pressure filtration by a filter press to the crystallizing pot after decolorization, and adding an acid solution dropwise to adjust the pH value;
step seven: and centrifugally dewatering after the dropwise adding is finished to obtain a filter cake, washing the filter cake with water until a liquid outlet is clarified, centrifugally drying, discharging and drying to obtain a sulfadoxine finished product.
2. The process according to claim 1, wherein the preparation process comprises the following steps: and in the step one, technical management personnel carry out technical interaction on the technical scheme after approval to the working personnel, sign the technical scheme and store the technical scheme by both the technical management personnel and the working personnel in a filing manner.
3. The process according to claim 1, wherein the preparation process comprises the following steps: in the third step, the temperature is controlled to be 45-55 ℃ for reaction for 4 hours, the temperature is cooled to be 25-30 ℃ for reaction for 15 hours, and then the temperature is controlled to be below 35 ℃.
4. The process according to claim 1, wherein the preparation process comprises the following steps: after decarbonylation is carried out for 4 hours in the fourth step, the Kjeldahl substance is distilled under reduced pressure to obtain 125.5g of Kjeldahl substance, which is 90-120 ℃/750mmHg or 145 ℃/720 and 750mmHg at 120-; the yield thereof was found to be 89%.
5. The process according to claim 1, wherein the preparation process comprises the following steps: heating to 80-85 ℃ for 3 hours in the sixth step, and stirring while heating at the stirring speed of 120-140 r/min.
6. The process according to claim 1, wherein the preparation process comprises the following steps: and the step five, the pH value is adjusted to 9.0-12 by using glacial acetic acid solution with the mass percentage concentration of 20-40%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112457259A (en) * | 2020-12-08 | 2021-03-09 | 重庆康乐制药有限公司 | Preparation method of sulfadoxine |
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2020
- 2020-05-11 CN CN202010391228.3A patent/CN111410635A/en active Pending
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| CN102304095A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102391189A (en) * | 2011-09-23 | 2012-03-28 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102391190A (en) * | 2011-09-30 | 2012-03-28 | 常熟市金申医化制品有限责任公司 | Method for preparing sulfadoxine |
| CN104557735A (en) * | 2014-12-04 | 2015-04-29 | 重庆康乐制药有限公司 | Preparation method of high-purity sulfadoxine |
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| CN112457259A (en) * | 2020-12-08 | 2021-03-09 | 重庆康乐制药有限公司 | Preparation method of sulfadoxine |
| CN112457259B (en) * | 2020-12-08 | 2024-02-20 | 重庆康乐制药有限公司 | Preparation method of sulfadoxine |
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