CN115819290A - Preparation method of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate - Google Patents
Preparation method of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate Download PDFInfo
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Abstract
The invention relates to a preparation method of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate, which adopts photographic-grade hydroquinone, 95-98 percent of reagent-grade sulfuric acid and medical-grade or food-grade calcium carbonate as raw materials, and prepares a crude product water solution of 2, 5-dihydroxy benzene sulfonic acid calcium through sulfonation reaction, neutralization reaction, calcium sulfate crystal conversion and filtration of calcium sulfate dihydrate, the crude product water solution of 2, 5-dihydroxy benzene sulfonic acid calcium is decompressed and concentrated, and the concentrated solution is subjected to hydroquinone removal, water insoluble substance removal, water-soluble impurity removal and crystal water removal to form 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate; the calcium 2, 5-dihydroxybenzenesulfonate monohydrate prepared by the method is white in color, each quality index meets the standard of European pharmacopoeia, the yield is more than 90%, the preparation process steps are clear 262111, the reaction conditions are mild, the raw materials are easy to obtain, and the method is suitable for industrial production.
Description
Technical Field
The invention relates to the field of pharmaceutical industry, in particular to a preparation method of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate.
Background
Calcium 2, 5-dihydroxybenzenesulfonate was first marketed in 1971 by the company Carroin, france, and is a widely used agent for improving the microcirculation of the blood vessels internationally.
The 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate is used for preventing and treating various diseases caused by microcirculation disturbance, can reduce platelet adhesion and blood viscosity, reduce high permeability and flexibility of capillary, can antagonize active substances (such as histamine, 5-hydroxytryptamine, bradykinin and the like) for inducing increase of vascular permeability, and has the effects of improving tissue ischemia and hypoxia states, improving microcirculation disturbance and the like; the traditional Chinese medicine composition is mainly used for treating diabetic microangiopathy (retinopathy and glomerulosclerosis) and also used for various varicose veins, hemorrhoids, leg ulcers, pruritic dermatitis and the like caused by microcirculation disturbance, and is an ideal medicine which is generally accepted at present and is directly used for preventing and treating the diabetic microangiopathy.
Chinese patent document CN101880248B discloses a synthesis process for preparing calcium dobesilate hydrate by direct sulfonation of hydroquinone and concentrated sulfuric acid and neutralization reaction with calcium carbonate in aqueous solution; chinese patent document CN102219715B discloses a method for treating crude calcium dobesilate with an aqueous ethanol solution to obtain pharmaceutically acceptable high-purity calcium dobesilate.
The prior art disclosed has the following defects:
the milky dense fine-grained reactant generated by the neutralization of the sulfonated product and the calcium carbonate cannot be separated by a conventional filtration mode;
after concentration and crystallization, the water-soluble calcium dobesilate and water-soluble impurities exist in a non-solid solution form, polar impurities are attached to the surface of a calcium dobesilate crystal, the loss of the calcium dobesilate is caused by adopting a mode of dissolving and removing the polar impurities by C1 or C2 lower alcohol, and the yield is greatly reduced;
the calcium dobesilate belongs to a heat-sensitive compound, the calcium dobesilate is polymerized and deteriorated by higher operation temperature, and the post-treatment process for preparing the calcium dobesilate comprises the following steps: removing hydroquinone, removing water insoluble substances and water-soluble impurities, and strictly controlling the operation temperature is very important.
The calcium dobesilate monohydrate cannot be formed into a monohydrate by conventional reduced pressure heating and drying, and the calcium dobesilate monohydrate is polymerized to form a water-insoluble substance in the conventional reduced pressure heating and dehydration process.
Disclosure of Invention
The invention aims to provide a preparation method of 2, 5-dihydroxy calcium benzenesulfonate monohydrate, which adopts hydroquinone, sulfuric acid and calcium carbonate as raw materials, and prepares a crude water solution of 2, 5-dihydroxy calcium benzenesulfonate by sulfonation reaction, neutralization reaction, crystal transformation of calcium sulfate and filtration of calcium sulfate dihydrate.
The reaction formula is as follows:
removing hydroquinone, water insoluble substances, water soluble impurities and crystal water from the crude water solution of the calcium 2, 5-dihydroxybenzenesulfonate to form calcium 2, 5-dihydroxybenzenesulfonate monohydrate:
the object of the invention is achieved by a preparation method, which is characterized by comprising the following steps:
(1) Synthesis of calcium 2, 5-dihydroxybenzenesulfonate: adding sulfuric acid into a reaction device, adding hydroquinone while stirring and cooling, uniformly mixing, heating to 70-80 ℃, and reacting to generate 2, 5-dihydroxy benzene sulfonic acid; adding deionized water, heating to 70-80 ℃ to completely dissolve reactants, cooling to normal temperature, adding calcium carbonate slurry, adjusting the pH value of the neutralization reaction end point to 3.5-4.0, and obtaining calcium sulfate feed liquid containing water-soluble 2, 5-dihydroxy benzene sulfonic acid calcium;
(2) Separating calcium sulfate: vacuumizing the reaction device to the pressure lower than-0.90 atm, filling nitrogen, heating the calcium sulfate feed liquid containing water-soluble calcium 2, 5-dihydroxybenzenesulfonate, heating to 70-80 ℃ to convert the calcium sulfate dihydrate into calcium sulfate hemihydrate, cooling to 30-40 ℃, and converting the calcium sulfate hemihydrate into the calcium sulfate dihydrate again; re-measuring the pH value, filtering, washing a filter cake by using a proper amount of deionized water, and collecting filtrate and washing liquor to obtain a crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution;
(3) Removing hydroquinone: adding the crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution into a reduced pressure distillation device, heating and distilling under reduced pressure until crystals are separated out, cooling the distillation residue, eliminating negative pressure, and adding a C5-C6 ester solvent; changing a reduced pressure distillation device into a reduced pressure azeotropic dehydration device, heating up under reduced pressure for azeotropic distillation until no water is separated out from a water separator, filtering, washing a filter cake by using a proper amount of C5-C6 ester solvent, and drying the filter cake in vacuum to obtain a crude product of the calcium 2, 5-dihydroxy benzene sulfonate polyhydrate;
(4) Removing water insoluble substances: adding deionized water into the crude product of the calcium 2, 5-dihydroxybenzenesulfonate polyhydrate, dissolving at normal temperature, and filtering with a micron-sized filter element filter to obtain transparent filtrate;
(5) Removing water-soluble impurities: adding transparent filtrate into a reduced pressure distillation device, concentrating the filtrate until crystals are separated out, stopping distillation, cooling the concentrated solution, eliminating negative pressure, filtering, and vacuum-drying filter cakes; collecting filtrate and washing liquid, and performing reduced pressure concentration, cooling crystallization, filtration, washing and vacuum drying operations again; adding C3-C4 alcohol into the dried filter cake to make slurry, filtering, washing the filter cake by using a proper amount of C3-C4 alcohol, and drying the filter cake in vacuum to obtain a refined 2, 5-dihydroxy calcium benzenesulfonate hydrate;
(6) Removing crystal water: adding a refined calcium 2, 5-dihydroxybenzenesulfonate hydrate and a C5-C6 ester solvent into the reduced-pressure azeotropic dehydration device, heating under reduced pressure for azeotropic distillation until no water is separated out from the water separator, cooling, eliminating negative pressure, filtering, and drying a filter cake in vacuum to obtain a finished product of the calcium 2, 5-dihydroxybenzenesulfonate hydrate.
Preferably, in the step (2), the reaction conditions are as follows: heating to 75-80 ℃ under the protection of nitrogen, and stirring for 2h; cooling to 30-35 ℃, re-measuring the pH value, and stirring for 2h under heat preservation; the filtering temperature is 15-20 ℃.
Preferably, in the step (3), the reduced pressure distillation temperature is 40-45 ℃, the concentration is carried out until crystals are separated out, and the temperature is cooled to 20-25 ℃ to eliminate negative pressure; the reduced pressure azeotropic distillation is carried out under the conditions that the pressure is less than-0.90 atm, the reflux temperature is 35-40 ℃, the azeotropic distillation is carried out until no water is separated out from the water separator, the distillation is stopped, the temperature is cooled to 15-20 ℃, the negative pressure is eliminated, and the filtration is carried out; the filter cake drying conditions were: vacuum drying for 3h at 40-45 ℃; the C5-C6 ester solvent is butyl acetate.
Preferably, in the step (4), the dissolving temperature is 10-30 ℃; the aperture of the filter element is less than 1 μm.
Preferably, in the step (5), the reduced pressure concentration condition is that the pressure is less than-0.90 atm and the temperature is 40-45 ℃; cooling the residue to 20-25 deg.c and eliminating negative pressure; C3-C4 alcohol pulping is carried out under the condition of stirring for 1h at the temperature of 5-10 ℃; the drying condition is vacuum drying for 4 hours at 40-45 ℃; the C3-C4 alcohol is isobutanol.
Preferably, in the step (5), the weight ratio of the C3-C4 alcohol to the filter cake is 0.6-0.8: 1.
preferably, in the step (6), the solvent is added, then the mixture is cooled to less than 20 ℃, the temperature is increased, the azeotropic distillation condition is that the pressure is less than-0.90 atm, and the reflux temperature is 35-45 ℃; the drying condition of the filter cake is vacuum drying for 3 hours at the temperature of 40-45 ℃; C5-C6 ester is butyl acetate; the weight ratio of the C5-C6 ester to the filter cake is 2-3: 1.
the preparation method of the invention solves the following problems:
1) The preparation method disclosed by the invention prepares the 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate by selecting a decompression azeotropic dehydration solvent and strictly controlling the operation temperature.
2) The preparation method disclosed by the invention enables fine crystal of calcium sulfate to grow into large-particle crystal through crystal transformation operation of calcium sulfate in dihydrate and hemihydrate crystals, thereby realizing effective separation of calcium sulfate and the calcium 2, 5-dihydroxy benzene sulfonate aqueous solution.
3) The preparation method disclosed by the invention adopts C3-C4 alcohol to wash polar impurities attached to the surface of the crude calcium 2, 5-dihydroxybenzenesulfonate crystal, wherein the C3-C4 alcohol has good solubility on the polar impurities, and the solubility on the calcium 2, 5-dihydroxybenzenesulfonate is extremely low; meanwhile, the proper boiling point of the C3-C4 alcohol has high safety for vacuum drying of the heat-sensitive calcium 2, 5-dihydroxybenzenesulfonate.
4) The preparation method disclosed by the invention is characterized in that a calcium 2, 5-dihydroxybenzenesulfonate monohydrate product formed by carrying out post-treatment on a crude calcium 2, 5-dihydroxybenzenesulfonate hydrate product through removing hydroquinone, removing water-insoluble substances, removing water-soluble impurities and removing crystal water is white in color, all quality indexes meet the standards of European pharmacopoeia, and the yield is more than 90%.
Detailed Description
The present invention is further illustrated by the following examples.
The specific embodiments described herein are merely illustrative of the invention and do not delimit the invention.
Unless otherwise specified, the chemical reagents and materials of the present invention are either commercially available or synthesized from commercially available starting materials. Wherein hydroquinone is photographic grade, sulfuric acid is reagent grade, and calcium carbonate is medical grade or food grade.
Example 1
(1) Synthesis of calcium 2, 5-dihydroxybenzenesulfonate: adding 150g of sulfuric acid into a reaction device, cooling by cooling water, adding 120g of hydroquinone while stirring, continuously stirring for 15min, heating to 70 ℃, stopping stirring, and keeping the temperature for 1h; dropping 120ml of deionized water, preserving heat for 1h at 70 ℃, restarting stirring to completely dissolve reactants; cooling to 30 ℃, adding calcium carbonate water slurry in batches until the pH value of the feed liquid is 3.5, and obtaining water-soluble calcium sulfate feed liquid of the 2, 5-dihydroxy benzene sulfonate;
(2) Separating calcium sulfate: vacuumizing the reaction device to the pressure less than-0.90 atm, filling nitrogen, heating the water-soluble calcium sulfate feed liquid of the calcium 2, 5-dihydroxy benzene sulfonate, heating to 70 ℃, and stirring for 2 hours; cooling to 30 ℃, repeatedly measuring the pH value, keeping the temperature and stirring for 2h, cooling to 10 ℃, filtering, washing a filter cake with 60ml of distilled water, and combining filtrate and washing liquor to obtain a crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution;
(3) Removing hydroquinone: adding the crude water solution of the calcium 2, 5-dihydroxybenzenesulfonate into a reduced pressure distillation device, distilling at 40 ℃ under reduced pressure until crystals are separated out, cooling the distillation residue to 20 ℃, and eliminating negative pressure; changing the reduced pressure distillation device into a reduced pressure azeotropic dehydration device, adding 360ml of ethyl propionate, heating and carrying out azeotropic distillation under the pressure of-0.91 atm until no water is separated out from the water separator; cooling the materials to 15 ℃, eliminating negative pressure, filtering, washing a filter cake by using a proper amount of ethyl propionate, and carrying out vacuum drying on the filter cake for 2 hours at 40 ℃ to obtain 40.2g of a crude product of the calcium 2, 5-dihydroxy benzene sulfonate polyhydrate;
(4) Removing water insoluble substances: adding equal weight of deionized water into the crude calcium 2, 5-dihydroxybenzenesulfonate hydrate, controlling the temperature to be 20 ℃, stirring to completely dissolve the calcium 2, 5-dihydroxybenzenesulfonate, and pressurizing and filtering by a micron-sized filter element filter to obtain transparent filtrate;
(5) Removing water-soluble impurities: adding transparent filtrate into a reduced pressure distillation device, concentrating under reduced pressure at 40 deg.C, stopping distillation when crystal is separated out, cooling the concentrated solution to 15 deg.C, eliminating negative pressure, filtering, and vacuum drying filter cake at 40 deg.C for 4 hr; collecting the filtrate, and performing reduced pressure concentration, cooling crystallization, filtration, washing and vacuum drying operations again;
adding n-propanol of which the weight is 0.8 time that of the filter cake into the dried filter cake, cooling to 5 ℃ while stirring, stirring for 1h, filtering, washing the filter cake by using a proper amount of n-propanol, and drying the filter cake in vacuum for 3h at 40 ℃ to obtain a refined product of the calcium 2, 5-dihydroxy benzene sulfonate polyhydrate;
(6) Removing crystal water: adding a refined 2, 5-dihydroxy benzene sulfonic acid calcium hydrate into a decompression azeotropic dehydration device, adding 3 times of ethyl propionate by weight of a filter cake, controlling the temperature to be 18 ℃, heating under negative pressure of-0.93 atm, and performing azeotropic dehydration until no water is separated from a water separator; cooling the feed liquid, eliminating negative pressure, filtering, and vacuum drying the filter cake at 40 ℃ for 3h to obtain 35.9g of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate with the yield of 90.6%.
Example 2
(1) Synthesis of calcium 2, 5-dihydroxybenzenesulfonate: adding 160g of reagent into a reaction device, cooling by cooling water, adding 120g of hydroquinone while stirring, continuously stirring for 15min, heating to 75 ℃, stopping stirring, and keeping the temperature for 1h; dropping 120ml of deionized water, preserving heat for 1h at 70 ℃, restarting stirring to completely dissolve reactants; cooling to 30 ℃, adding calcium carbonate water slurry in batches until the pH value of the feed liquid is 3.7, and obtaining water-soluble calcium sulfate feed liquid of the 2, 5-dihydroxy benzene sulfonate;
(2) Separating calcium sulfate: vacuumizing the reaction device to the pressure less than-0.90 atm, filling nitrogen, heating the water-soluble calcium sulfate feed liquid of the calcium 2, 5-dihydroxy benzene sulfonate, heating to 75 ℃, and stirring for 2 hours; cooling to 35 ℃, repeatedly measuring the pH value, keeping the temperature and stirring for 2h, cooling to 15 ℃, filtering, washing a filter cake with 60ml of distilled water, and combining filtrate and washing liquor to obtain a crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution;
(3) Removing hydroquinone: adding the crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution into a reduced pressure distillation device, distilling at 45 ℃ under reduced pressure until crystals are separated out, cooling the distillation residue to 25 ℃, and eliminating negative pressure; changing the reduced pressure distillation device into a reduced pressure azeotropic dehydration device, adding 360ml of butyl acetate, heating and carrying out azeotropic distillation under the pressure of-0.97 atm until no water is separated out from the water separator; cooling the materials to 20 ℃, eliminating negative pressure, filtering, washing a filter cake by using a proper amount of butyl acetate, and carrying out vacuum drying on the filter cake for 3 hours at the temperature of 45 ℃ to obtain 40.6g of a crude product of the calcium 2, 5-dihydroxy benzene sulfonate polyhydrate;
(4) Removing water insoluble substances: adding equal weight of deionized water into the crude calcium 2, 5-dihydroxybenzenesulfonate hydrate, controlling the temperature to be 25 ℃, stirring to completely dissolve the calcium 2, 5-dihydroxybenzenesulfonate, and pressurizing and filtering by a micron-sized filter element filter to obtain transparent filtrate;
(5) Removing water-soluble impurities: adding transparent filtrate into a reduced pressure distillation device, concentrating under reduced pressure at 40 deg.C, stopping distillation when crystal is separated out, cooling the concentrated solution to 20 deg.C, eliminating negative pressure, filtering, and vacuum drying filter cake at 40 deg.C for 4 hr; collecting the filtrate, and performing reduced pressure concentration, cooling crystallization, filtration, washing and vacuum drying operations again;
adding isobutanol with the weight 0.8 times that of the filter cake into the dried filter cake, cooling to 10 ℃ while stirring, stirring for 1h, filtering, washing the filter cake with a proper amount of isobutanol, and drying the filter cake at 45 ℃ for 4h in vacuum to obtain a refined 2, 5-dihydroxy calcium benzenesulfonate hydrate;
(6) Removing crystal water: adding a refined 2, 5-dihydroxy benzene sulfonic acid calcium polyhydrate product into a decompression azeotropic dehydration device, adding 3 times of butyl acetate by weight of a filter cake, controlling the temperature to be 18 ℃, heating under negative pressure of-0.97 atm, and performing azeotropic dehydration until no water is separated out from a water separator; cooling the feed liquid, eliminating negative pressure, filtering, and vacuum drying the filter cake for 3h at 45 ℃ to obtain 36.2g of 2, 5-dihydroxy benzene sulfonic acid calcium monohydrate with the yield of 91.3 percent.
Example 3
(1) Synthesis of calcium 2, 5-dihydroxybenzenesulfonate: adding 160g of reagent into a reaction device, cooling by cooling water, adding 120g of hydroquinone while stirring, continuously stirring for 15min, heating to 70 ℃, stopping stirring, and keeping the temperature for 1h; dropping 120ml of deionized water, preserving heat for 1h at 70 ℃, restarting stirring to completely dissolve reactants; cooling to 30 ℃, adding calcium carbonate water slurry in batches until the pH value of the feed liquid is 5.0, and obtaining water-soluble calcium sulfate feed liquid of the 2, 5-dihydroxy benzene sulfonate;
(2) Separating calcium sulfate: vacuumizing the reaction device to the pressure less than-0.90 atm, filling nitrogen, heating the water-soluble calcium sulfate feed liquid of the calcium 2, 5-dihydroxy benzene sulfonate, heating to 70 ℃, and stirring for 2 hours; cooling to 30 ℃, re-measuring the pH value, and stirring for 2h under heat preservation; cooling to 10 ℃, filtering, washing a filter cake by 60ml of distilled water, and combining filtrate and washing liquor to obtain a crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution;
(3) Removing hydroquinone: adding the crude water solution of the calcium 2, 5-dihydroxybenzenesulfonate into a reduced pressure distillation device, distilling at 40 ℃ under reduced pressure until crystals are separated out, cooling the distillation residue to 20 ℃, and eliminating negative pressure; changing the reduced pressure distillation device into a reduced pressure azeotropic dehydration device, adding 360ml of ethyl propionate, heating and carrying out azeotropic distillation under the pressure of-0.91 atm until no water is separated out from the water separator; cooling the materials to 15 ℃, eliminating negative pressure, and forming fine crystals from the crude product of the calcium 2, 5-dihydroxy benzene sulfonate which is difficult to filter.
The reaction end point pH value in the step (1) has an obvious influence on the crystal growth of the calcium 2, 5-dihydroxybenzenesulfonate monohydrate in the step (3).
In the step (1), with the addition of calcium carbonate, the pH value rises, and the color of the feed liquid shows the following changes: purple black → maotai red → orange red → dark yellow → light yellow.
At pH =4.45, the feed liquid turned from violet black to dark reddish brown.
When the feed liquid with the pH value of more than 4.45 is concentrated in the step (3), the calcium 2, 5-dihydroxybenzenesulfonate is easy to separate out multi-hydrate fine crystals, and the larger the pH value is, the finer the crystals are.
When the pH value is less than 4.45, the crystal growth of the calcium 2, 5-dihydroxybenzenesulfonate monohydrate is good, but when the pH value is less than 3.5, the crystal is sticky and has slight wall sticking phenomenon.
The products obtained in example 1 and example 2 were tested according to the standard of the European pharmacopoeia, and the test results are shown in Table 1.
TABLE 1
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (7)
1. A method for preparing calcium 2, 5-dihydroxybenzenesulfonate monohydrate, characterized in that said method comprises the following steps:
(1) Synthesis of calcium 2, 5-dihydroxybenzenesulfonate: adding sulfuric acid into a reaction device, adding hydroquinone while stirring and cooling, uniformly mixing, heating to 70-80 ℃, and reacting to generate 2, 5-dihydroxybenzenesulfonic acid; adding deionized water, heating to 70-80 ℃ to completely dissolve reactants, cooling to normal temperature, adding calcium carbonate slurry, adjusting the pH value of the neutralization reaction end point to 3.5-4.0, and obtaining calcium sulfate feed liquid containing water-soluble 2, 5-dihydroxy benzene sulfonic acid calcium;
(2) Separating calcium sulfate: vacuumizing the reaction device to the pressure lower than-0.90 atm, filling nitrogen, heating the calcium sulfate feed liquid containing water-soluble calcium 2, 5-dihydroxybenzenesulfonate, heating to 70-80 ℃ to convert the calcium sulfate dihydrate into calcium sulfate hemihydrate, cooling to 30-40 ℃, and converting the calcium sulfate hemihydrate into the calcium sulfate dihydrate again; re-measuring the pH value, filtering, washing a filter cake with a proper amount of deionized water, and collecting filtrate and washing liquor to obtain a crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution;
(3) Removing hydroquinone: adding the crude calcium 2, 5-dihydroxybenzenesulfonate aqueous solution into a reduced pressure distillation device, heating and distilling under reduced pressure until crystals are separated out, cooling the distillation residue, eliminating negative pressure, and adding a C5-C6 ester solvent; changing a reduced pressure distillation device into a reduced pressure azeotropic dehydration device, heating up under reduced pressure for azeotropic dehydration until no water is separated out from a water separator, filtering, washing a filter cake by using a proper amount of C5-C6 ester solvent, and drying the filter cake in vacuum to obtain a crude product of the calcium 2, 5-dihydroxy benzene sulfonate polyhydrate;
(4) Removing water insoluble substances: adding deionized water into the crude product of the calcium 2, 5-dihydroxybenzenesulfonate polyhydrate, dissolving at normal temperature, and filtering with a micron-sized filter element filter to obtain transparent filtrate;
(5) Removing water-soluble impurities: adding transparent filtrate into a reduced pressure distillation device, concentrating the filtrate until crystals are separated out, stopping distillation, cooling the concentrated solution, eliminating negative pressure, filtering, and vacuum-drying filter cakes; collecting the filtrate and washing liquid, and performing reduced pressure concentration, cooling crystallization, filtration, washing and vacuum drying operations again; adding C3-C4 alcohol into the dried filter cake to make slurry, filtering, washing the filter cake by using a proper amount of C3-C4 alcohol, and drying the filter cake in vacuum to obtain a refined 2, 5-dihydroxy calcium benzenesulfonate hydrate;
(6) Removing crystal water: adding a refined calcium 2, 5-dihydroxybenzenesulfonate hydrate and a C5-C6 ester solvent into a decompression azeotropic dehydration device, heating under reduced pressure for azeotropic distillation until no water is separated out from the water separator, cooling, eliminating negative pressure, filtering, and drying a filter cake in vacuum to obtain a finished product of the calcium 2, 5-dihydroxybenzenesulfonate hydrate.
2. The method for preparing calcium 2, 5-dihydroxybenzenesulfonate monohydrate according to claim 1, characterized in that in step (2), the reaction conditions are: heating to 70-80 ℃ under the protection of nitrogen, and stirring for 2-3 h; cooling to 30-40 ℃, re-measuring the pH value, and stirring for 2-3 h under heat preservation; the filtering temperature is 10-20 ℃.
3. The method for preparing the calcium 2, 5-dihydroxybenzenesulfonate monohydrate according to claim 1, characterized in that, in the step (3), the reduced pressure distillation temperature is 40-50 ℃, the calcium 2, 5-dihydroxybenzenesulfonate monohydrate is concentrated until crystals are separated out, and the calcium 2, 5-dihydroxybenzenesulfonate monohydrate is cooled to 20-30 ℃ to eliminate negative pressure; the reduced pressure azeotropic distillation is carried out under the conditions that the pressure is less than-0.90 atm, the reflux temperature is 35-40 ℃, the azeotropic distillation is carried out until no water is separated out from the water separator, the distillation is stopped, the temperature is cooled to 15-25 ℃, the negative pressure is eliminated, and the filtration is carried out; the drying condition of the filter cake is vacuum drying for 2 to 3 hours at the temperature of between 40 and 50 ℃; the C5-C6 ester solvent is ethyl propionate or butyl acetate.
4. The method for preparing calcium 2, 5-dihydroxybenzenesulfonate monohydrate according to claim 1, characterized in that in step (4), the dissolution temperature is 0-40 ℃; the aperture of the filter element is less than 1 μm.
5. The method for preparing calcium 2, 5-dihydroxybenzenesulfonate monohydrate according to claim 1, characterized in that, in step (5), the concentration under reduced pressure is carried out under a pressure of < -0.90atm and at a temperature of 40-50 ℃; cooling the residue to 20-25 deg.c and eliminating negative pressure; C3-C4 alcohol pulping is carried out under the condition of stirring at 5-15 ℃ for 1-2 h; the drying condition is vacuum drying for 3-4 h at 40-50 ℃; the C3-C4 alcohol is n-propanol or isobutanol.
6. The method for preparing the calcium 2, 5-dihydroxybenzenesulfonate monohydrate according to claim 1, characterized in that, in the step (5), the weight ratio of the C3-C4 alcohol to the filter cake is 0.6-1.2: 1.
7. the method of claim 1, wherein the calcium 2, 5-dihydroxybenzenesulfonate monohydrate is prepared by the step (6) of adding a solvent, cooling to < 20 ℃, heating under azeotropic distillation conditions of pressure < -0.90atm and reflux temperature of 35-45 ℃; the drying condition of the filter cake is vacuum drying for 3-4 h at 40-50 ℃; C5-C6 ester is butyl acetate or ethyl propionate; the weight ratio of the C5-C6 ester to the filter cake is 2-5: 1.
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