CN109422642B - Refining method of benzoic acid, production method and equipment of pharmaceutical grade sodium benzoate - Google Patents
Refining method of benzoic acid, production method and equipment of pharmaceutical grade sodium benzoate Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
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Abstract
The invention discloses a refining method of benzoic acid, a production method and equipment of pharmaceutical-grade sodium benzoate. The refining steps of the benzoic acid are as follows: s1, uniformly mixing the organic solvent, water and the crude benzoic acid, and heating until the crude benzoic acid is dissolved to obtain a mixed solution; the organic solvent is one or more of methanol, ethanol, N-propanol, isopropanol, butanol, formic acid, acetic acid, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, acetone and butanone; the mass ratio of the organic solvent to the water is (0.2-5) to 1; the mass ratio of the mixed solvent to the crude benzoic acid is (1-3): 1; s2, stirring the mixed solution at the temperature of-20 ℃ for crystallization for 3-24 hours; s3, filtering to obtain filtrate and solid, and completely recovering the filtrate to S1 as a solvent. The refined benzoic acid can be directly used for producing medicinal sodium benzoate, and the yield of the obtained sodium benzoate is over 90 percent, and the purity of the obtained sodium benzoate is over 99.9 percent.
Description
Technical Field
The invention relates to the field of pharmaceutical chemicals, in particular to a refining method of benzoic acid, a production method of pharmaceutical grade sodium benzoate and equipment.
Background
Sodium benzoate, also known as sodium benzoate, is odorless or slightly benzoin-smelling, is easily soluble in water, is a sodium salt of benzoic acid, and is mainly used in the fields of feed, food and medicine. Sodium benzoate is used as a pharmaceutic adjuvant, and is mainly used as a bacteriostatic agent and a preservative in a pharmaceutical preparation. The sodium benzoate has good effect on saccharomycetes, mould and part of bacteria under the acidic condition, so the sodium benzoate is widely applied to the field of medicines.
At present, the domestic technology for producing sodium benzoate is that toluene is first oxidized by air, the benzoic acid is separated from the product by physical method (rectification or recrystallization), and then the benzoic acid is neutralized by sodium carbonate, sodium bicarbonate or sodium hydroxide to prepare sodium benzoate. In the whole production process, benzoic acid and sodium benzoate respectively need to be refined, and the method has many repeated links, long process flow, large raw material consumption and high energy consumption.
The benzoic acid refining process mainly adopts physical processes, such as rectification, sublimation crystallization, melt crystallization, solution recrystallization, supercritical extraction and the like. Among them, rectification, sublimation crystallization and melt crystallization require high-temperature treatment, which undoubtedly increases much energy consumption.
Chinese patent application (CN 102001935 a) discloses a method for refining benzoic acid by using a melt crystallization method, but the method of the patent application is to raise the temperature of benzoic acid mother liquor to 120 ℃ first, and then slowly lower the temperature for crystallization. The refining process is complicated, long in time and high in energy consumption.
The closest to the technology of the present application is the chinese patent application (CN 106608819 a), which reports that a method of water back extraction is used to refine benzoic acid, and the technical principle of the method is actually the principle of recrystallization. However, the method needs a large amount of water in actual production, generates a large amount of waste water, takes away a large amount of benzoic acid and derivatives thereof in the waste water, has high COD value of the aqueous solution, causes large pollution of three wastes, consumes great raw materials, has high cost and has low equipment operation efficiency, so the treatment amount of the crude benzoic acid is small.
The production method of sodium benzoate adopts the neutralization of benzoic acid with sodium carbonate, sodium bicarbonate or sodium hydroxide. However, most of these processes use industrial-grade benzoic acid (purity is 98% or more) as a raw material, and after the neutralization reaction is completed, an adsorbent is added to purify and refine the benzoic acid (see chinese patent application CN 103613499A, CN 1796355A, CN 105646183A, CN 101612551B, CN 104557522 a), so that a process of filtering and removing the adsorbent is required. This undoubtedly also increases the number of operating steps and increases the production costs.
Therefore, in view of the disadvantages of the prior art, there is a need to develop a preparation method which has simple process flow, low energy consumption and low production cost and is suitable for large-scale industrial production of pharmaceutical-grade sodium benzoate.
Disclosure of Invention
The invention aims to overcome the defects of complex refining process, high cost, small treatment capacity, high energy consumption, complex process, small treatment capacity, high production cost and the like in the production process of the sodium benzoate in the prior art, and provides a refining method of the benzoic acid, a production method of the pharmaceutical-grade sodium benzoate and equipment. The production method provided by the invention has the advantages of simple process flow, low energy consumption and low production cost, can meet the requirements of pharmacopoeia, and is suitable for industrial production.
The invention provides a refining method of benzoic acid, which comprises the following steps:
s1, uniformly mixing the organic solvent, water and the crude benzoic acid, and heating until the crude benzoic acid is dissolved to obtain a mixed solution; the organic solvent is one or more of methanol, ethanol, N-propanol, isopropanol, butanol, formic acid, acetic acid, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, acetone and butanone; the mass ratio of the organic solvent to the water is (0.2-5) to 1; the mass ratio of the mixed solvent to the crude benzoic acid is (1-3): 1;
s2, stirring and crystallizing the mixed solution at the temperature of-20 ℃ for 3-24 hours;
s3, filtering to obtain filtrate and solid, wherein the filtrate is completely recycled to the step S1 to be used as a solvent for dissolving the crude benzoic acid, and the solid is refined benzoic acid.
In step S1, the crude benzoic acid is a conventional chemical raw material in the art, and has a purity of generally greater than 98% and a water content of less than 1%.
In step S1, the organic solvent is preferably one or more of methanol, ethanol, n-propanol, isopropanol, acetone, and butanone. In addition, the organic solvents are all technical grade unless otherwise specified.
In step S1, the mass ratio of the organic solvent to the water is preferably (0.5-1): 1. In addition, the mixed solvent refers to a mixture of an organic solvent and water.
In step S1, the heating temperature is set to a temperature of 50 to 80 ℃ for the purpose of dissolving all the crude benzoic acid.
In step S2, the stirring crystallization temperature is preferably 5 to 20 ℃, and the stirring crystallization time is preferably 3 to 6 hours.
In step S2, the stirring speed of the stirring crystallization is a conventional parameter in the art, preferably 50 to 400r/min, and more preferably 50 to 150 r/min.
In step S3, when all of the filtrate is recovered to step S1 as a solvent, it is preferable to supplement the solvent mixture to the filtrate according to the quality of the recovered filtrate so as to satisfy the conditions defined in step S1: namely the mass ratio of the organic solvent to the water is (0.2-5) to 1; the mass ratio of the mixed solvent to the crude benzoic acid is (1-3): 1.
The invention also provides a production method of the medicinal sodium benzoate, which comprises the following steps: directly and uniformly mixing the refined benzoic acid with a NaOH solution, and reacting to obtain a reaction solution; and directly concentrating and drying the reaction solution to obtain the medicinal sodium benzoate.
In the present invention, it is preferable that the purified benzoic acid is directly involved in the synthesis of sodium benzoate without drying.
In the invention, the addition amount of the NaOH solution is a conventional parameter in the field, and preferably the pH value of the reaction solution is adjusted to 7.8-8.0.
In the present invention, it is preferable that the reaction solution is directly concentrated and dried without adding an adsorbent.
In the present invention, the concentration and drying are preferably performed until the loss on drying is 1.5% or less, more preferably until the loss on drying is 0.8% or less.
The invention also provides a production device of the medicinal sodium benzoate, which comprises the following components:
the dissolving kettle is provided with a crude benzoic acid feeding hole, an organic solvent feeding hole, a water feeding hole and a mixed solution discharging hole;
a feeding port of the crystallization kettle is connected with a discharge port of the mixed solution;
a feed inlet of the filtering device is connected with a discharge outlet of the crystallization kettle, and a liquid outlet of the filtering device is connected with the organic solvent feed inlet;
The solid material outlet of the filtering device is connected with the neutralization reaction kettle, and the neutralization reaction kettle is also connected with a NaOH solution feed inlet;
and the drying device is connected with a discharge hole of the neutralization reaction kettle.
Preferably, the crude benzoic acid feed port is connected with a crude benzoic acid supply system, the organic solvent feed port is connected with an organic solvent storage tank, and the water feed port is connected with a water pipeline.
Preferably, the crystallization kettle is further provided with a stirring paddle and a temperature probe rod.
Preferably, the neutralization reaction kettle is also provided with a stirring paddle.
Preferably, the NaOH solution feed inlet is also connected with an alkali liquor storage tank.
On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows:
(1) the equipment of the invention organically combines a benzoic acid refining device and a medical grade sodium benzoate synthesizing device. The production process is simple and easy to operate.
(2) The refining operation of recrystallization of the benzoic acid is carried out through a mixed system of water and an organic solvent, the benzoic acid with higher purity is obtained, and the benzoic acid can be directly used for producing medicinal sodium benzoate, so that the drying process of the benzoic acid and the adsorption process in the production process of the sodium benzoate are eliminated. And the mother liquor after recrystallization can be recovered and reused for feeding of the next batch, so that the production yield of sodium benzoate is improved, and the production cost is saved.
(3) The method has high yield of sodium benzoate, which can reach more than 90%. The purity of the produced sodium benzoate is high and can reach more than 99.9 percent. Thus realizing large-scale industrialized production of sodium benzoate products meeting pharmacopoeia standards.
Drawings
FIG. 1 is a liquid chromatogram of benzoic acid from the examples.
FIG. 2 is a liquid chromatogram of sodium benzoate in the example.
Fig. 3 is a schematic view of a production facility of sodium benzoate in example 9 of this application.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
In the following examples, the purity of benzoic acid and sodium benzoate was measured by HPLC method, and the equipment type, test method and purity calculation method were as follows:
the HPLC detection method adopts Agilent 1260 high performance liquid chromatograph and an automatic sample injector. The chromatographic conditions are as follows:
a chromatographic column: diamonsil C18 column (4.6X 150mm, 5 μm); mobile phase: methanol: 1% acetic acid solution ═ 3: 7; flow rate: 1.2 mL/min; column temperature: 40 ℃; detection wavelength: 228 nm; sample introduction amount: 20 mu L of the solution; operating time: and (3) 30 min. The retention time of the main peak of benzoic acid under this condition is about 6.6min, as shown in fig. 1. The retention time of the main peak of sodium benzoate under the condition is about 6.6min, which is shown in figure 2.
The concrete method for measuring the content of the benzoic acid and the sodium benzoate comprises the following steps: taking a test sample and a proper amount of benzoic acid (or sodium benzoate) reference, adding methanol: a1% acetic acid solution (3:7) was dissolved and prepared to contain about 0.1mg of the solution per 1mL as a test and control solution. Precisely measuring 20 μ L of each of the test solution and the reference solution, respectively injecting into a liquid chromatograph, and recording chromatogram. The way of calculating the content of benzoic acid (or sodium benzoate) in the test sample is as follows:
results ═ Au/As (Cs/Cu) 100%
Wherein, Au is the peak area of benzoic acid (or sodium benzoate) in the test sample;
as is the peak area of the benzoic acid (or sodium benzoate) reference;
cs is the concentration (mg/mL) of a benzoic acid (or sodium benzoate) reference substance;
cu is the concentration (mg/mL) of benzoic acid (or sodium benzoate) in the test sample.
In the following examples, the percentages are by mass unless otherwise specified.
Example 1
1 ton of methanol, 2 tons of water and 1 ton of crude benzoic acid were added to the dissolution vessel. Heated to 50 ℃ until the benzoic acid is completely dissolved and then transferred to a crystallization kettle. Cooling to 20 ℃ at the stirring speed of 150 r/min, and continuously crystallizing for 6 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. And adding NaOH solution into the neutralization reaction kettle until the pH value is 7.8. The solution is concentrated and dried to obtain 1.09 tons of sodium benzoate solid with the total yield of 92.3 percent.
Example 2
1 ton of ethanol, 1 ton of water and 1 ton of crude benzoic acid were added to the dissolution vessel. Heated to 70 ℃ until the benzoic acid is completely dissolved and then transferred to a crystallization kettle. Cooling to 5 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 4 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 8.0. The solution is concentrated and dried to obtain 1.11 tons of sodium benzoate solid with the total yield of 94.0 percent.
Example 3
1 ton of N, N-dimethylformamide, 1 ton of water and 2 tons of crude benzoic acid were added to the dissolution vessel. Heated to 75 ℃ until the benzoic acid was completely dissolved and then transferred to a crystallization kettle. Cooling to-20 ℃ at the stirring speed of 150 r/min, and continuously crystallizing for 3 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 7.8. The solution is concentrated and dried to obtain 2.16 tons of sodium benzoate solid with the total yield of 91.5 percent.
Example 4
To the dissolution vessel was added 0.75 ton of acetic acid, 1 ton of water and 1 ton of crude benzoic acid. Heated to 55 ℃ until the benzoic acid was completely dissolved and then transferred to a crystallization kettle. Cooling to-5 ℃ at a stirring speed of 130 r/min, and continuously crystallizing for 5 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 7.9. The solution is concentrated and dried to obtain 1.07 ton of sodium benzoate solid with the total yield of 90.7 percent.
Example 5
To the dissolution vessel were added 1 ton of acetone, 2 tons of water and 1.5 tons of crude benzoic acid. Heat to 50 ℃ until the benzoic acid is completely dissolved and then transfer to the crystallization kettle. Cooling to 0 ℃ at the stirring speed of 50 r/min, and continuously crystallizing for 4 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 7.8. The solution is concentrated and dried to obtain 1.61 tons of sodium benzoate solid with the total yield of 90.9 percent.
Example 6
To the dissolution vessel were added 0.75 ton of dimethyl sulfoxide, 1 ton of water and 0.7 ton of crude benzoic acid. Heated to 60 ℃ until the benzoic acid was completely dissolved and then transferred to a crystallization kettle. Cooling to 10 ℃ at the stirring speed of 80 r/min, and continuously crystallizing for 4.5 h. Transferring the solution to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid (namely refined benzoic acid) to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 8.0. The solution is concentrated and dried to obtain 0.76 ton of sodium benzoate solid with the total yield of 92.0 percent.
Example 7
In this example, the amount of methanol used was 0.4 ton, and the types, amounts and process conditions of the remaining raw materials were the same as those in example 1.
Example 8
In this example, the amount of water used was 0.2 ton, and the types, amounts and process conditions of the remaining raw materials were the same as those in example 1.
Example 9
Production equipment corresponding to the production method of the pharmaceutical grade sodium benzoate in the embodiment 1-8 is shown in fig. 3, and comprises the following steps:
the dissolving kettle is provided with a crude benzoic acid feeding hole, an organic solvent feeding hole, a water feeding hole and a mixed solution discharging hole;
a feeding hole of the crystallization kettle is connected with a discharging hole of the mixed solution;
a feed port of the filtering device is connected with a discharge port of the crystallization kettle, and a liquid outlet of the filtering device is connected with the organic solvent feed port;
the solid material outlet of the filtering device is connected with the neutralization reaction kettle, and the neutralization reaction kettle is also connected with a NaOH solution feed inlet;
and the drying device is connected with a discharge hole of the neutralization reaction kettle.
The crude benzoic acid feeding port is connected with a crude benzoic acid feeding system, the organic solvent feeding port is connected with an organic solvent storage tank, and the water feeding port is connected with a water pipeline.
The crystallization kettle is also provided with a stirring paddle and a temperature probe rod. The neutralization reaction kettle is also provided with a stirring paddle. The NaOH solution feed inlet is also connected with an alkali liquor storage tank.
Comparative example 1
Benzoic acid purification was performed according to CN 106608819 a, followed by synthesis of sodium benzoate according to the present method, for comparison. The method comprises the following specific steps: mixing the crude benzoic acid and 95% ethanol according to the mass ratio of 1:3, and stirring at normal temperature until the benzoic acid is completely dissolved. Adding 10 times of desalted water of crude benzoic acid, carrying out back extraction until all benzoic acid is crystallized and separated out, filtering and drying to obtain white benzoic acid crystals. The refined benzoic acid was added to NaOH solution until pH 8.0. The solution is concentrated and dried to obtain 7.53g of sodium benzoate solid with the total yield of 63.8 percent.
Comparative example 2
In the dissolution vessel were added 0.1 ton of ethanol, 1 ton of water and 1 ton of crude benzoic acid (benzoic acid was not completely dissolved). The solution and undissolved benzoic acid were transferred to a crystallization kettle. Cooling to 5 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 4 h. Transferring the filtrate to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 8.0. The solution is concentrated and dried to obtain 1.13 tons of sodium benzoate solid with the total yield of 95.7 percent.
Comparative example 3
1 ton of ethanol, 1 ton of water and 0.5 ton of crude benzoic acid were added to the dissolution vessel. Heated to 70 ℃ until the benzoic acid is completely dissolved and then transferred to a crystallization kettle. Cooling to 5 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 4 h. Transferring the filtrate to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid to a neutralization reaction kettle. NaOH solution was added to the neutralization kettle until pH 8.0. The solution is concentrated and dried to obtain 0.42 ton of sodium benzoate solid with the total yield of 71.2 percent.
Comparative example 4
1 ton of ethanol, 1 ton of water and 1 ton of crude benzoic acid were added to the dissolution vessel. Heated to 70 ℃ until the benzoic acid is completely dissolved and then transferred to a crystallization kettle. Cooling to 30 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 2 h. Transferring the filtrate to a filtering device, transferring the filtrate to a dissolving kettle after filtering, and transferring the solid to a neutralization reaction kettle. And adding NaOH solution into the neutralization reaction kettle until the pH value is 8.0. The solution is concentrated and dried to obtain 0.80 ton of sodium benzoate solid with the total yield of 67.8 percent.
Effect example 1
The examples 1 to 6 and comparative examples 1 to 4 were subjected to the examination of key items according to the examination items under the fourth part of sodium benzoate in the Chinese pharmacopoeia of the 2015 edition, and the results are shown in Table 1:
TABLE 1 comparison of results of examples 1 to 6 and comparative examples 1 to 4
In addition, the clarity, the drying weight loss and the purity of the sodium benzoate in the examples 7 and 8 are all in the pharmacopeia standard range, and the total yield of the sodium benzoate is slightly worse than that in the example 1.
In table 1, the purity data are all calculated according to the method of product purity in pharmacopoeia, i.e. the benzoic acid purity and the sodium benzoate purity are calculated by mass of the dried product, regardless of the water content. It can be seen from the test data in table 1 that the sodium benzoate products produced by the present invention all meet pharmaceutical grade standards. In contrast, in comparative example 1, the total yield is 63.8%, the content of sodium benzoate is 99.54%, and the implementation effect is lower than that of the invention.
Compared with CN 106608819A, the refining method of benzoic acid is further improved, firstly, the dosage of water is reduced, and the organic solvent and water are compounded into a mixed solvent, so that the dosage of water is reduced. Secondly, the treatment capacity of each batch of benzoic acid is increased, namely, the ratio of solvent to solute is reduced. Finally, the solvent in the production method is completely recycled, so that the steps of sewage treatment are reduced, and the production cost is greatly reduced.
Claims (2)
1. A method for refining benzoic acid is characterized by comprising the following steps:
adding 1 ton of ethanol, 1 ton of water and 1 ton of crude benzoic acid into a dissolving kettle; heating to 70 ℃ until the benzoic acid is completely dissolved, and then transferring to a crystallization kettle; cooling to 5 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 4 h; transferring the filtrate into a filtering device, transferring the filtrate into a dissolving kettle after filtering, and transferring the solid into a neutralization reaction kettle; the solid is refined benzoic acid.
2. A production method of medicinal sodium benzoate is characterized by comprising the following steps: adding 1 ton of ethanol, 1 ton of water and 1 ton of crude benzoic acid into a dissolving kettle; heating to 70 ℃ until the benzoic acid is completely dissolved, and then transferring to a crystallization kettle; cooling to 5 ℃ at the stirring speed of 100 r/min, and continuously crystallizing for 4 h; transferring the filtrate into a filtering device, transferring the filtrate into a dissolving kettle after filtering, and transferring the solid into a neutralization reaction kettle; the solid is refined benzoic acid;
adding NaOH solution into the neutralization reaction kettle until the pH value is 8.0; the solution is concentrated and dried to obtain 1.11 tons of sodium benzoate solid.
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| CN106608819A (en) * | 2015-10-22 | 2017-05-03 | 中国石油化工股份有限公司 | Method and device for refining benzoic acid |
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| CN106608819A (en) * | 2015-10-22 | 2017-05-03 | 中国石油化工股份有限公司 | Method and device for refining benzoic acid |
Non-Patent Citations (3)
| Title |
|---|
| 一种药用苯甲酸的制备;喻祥瑞等;《化学工程与装备》;20130331(第3期);第45-48+41页 * |
| 喻祥瑞等.一种药用苯甲酸的制备.《化学工程与装备》.2013,(第3期),第45-48+41页. * |
| 苯甲酸溶解度的测定及关联;刘江雏等;《郑州工业大学学报》;20010330;第22卷(第1期);第97-99页 * |
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