Preparation method of selenous acid and application thereof

Abstract

The application discloses a preparation method of selenous acid and application thereof, and belongs to the technical field of medical intermediates. The technical problem to be solved is to provide a preparation method of high-purity selenous acid in view of the degradation reaction of selenic acid at high temperature, low purity of selenous acid, high water content, and existence of other elemental selenium in products in the prior art. The technical solution points are as follows: the preparation method comprises the following steps: (1) mixing selenium dioxide with water, adding an oxidizing agent, stirring and reacting to obtain a crude product; and (2) filtering the crude product obtained in the step (1), adding an organic solvent to the filtrate for crystallization, and removing the solvent to obtain the product.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical intermediates technology, specifically to a method for preparing selenite and its application. Background Technology

[0002] Selenious acid (H₂SeO₃) is used in pharmaceutical preparations such as selenious acid injections and various trace element injections. Its medicinal value lies in its role as a trace element (selenium) supplement. Selenium is an essential trace element for maintaining normal human physiological functions. Selenious acid is chemically stable and has good bioavailability, making it a preferred selenium supplement in the pharmaceutical field. Currently, this substance is widely used in the research and production of injectable drugs, with typical preparations including selenious acid injections and various trace element injections. Clinically, it is mainly used as a selenium supplement to correct selenium deficiency in the human body.

[0003] Currently, industrial and laboratory preparation of selenite (H2SeO3) mainly uses elemental selenium or crude selenium as raw materials. The mainstream processes include nitric acid oxidation, oxygen / air oxidation-selenium dioxide hydration, and the route of recovering crude selenium from metallurgical by-products such as copper anode mud through wet / pyrometallurgical processes and then refining and converting it.

[0004] The nitric acid oxidation method is a traditional and commonly used approach: selenium powder is reacted with concentrated nitric acid at 50-70℃ to produce selenite acid, accompanied by nitrogen oxide tail gas; the reaction solution is then evaporated to remove acid, dissolved in water, filtered, concentrated, crystallized, and recrystallized to obtain selenite acid. This method is simple and requires low-level equipment, but nitric acid has strong oxidizing properties, produces many side reactions, and the product is prone to residual nitrates, unreacted selenium, and heavy metal impurities (Pb, As, Te, etc.). Typically, only industrial-grade products with a purity of 95%-98% can be obtained, which is difficult to meet the high purity requirements of pharmaceutical injections; at the same time, the tail gas treatment pressure is high, and the environmental risks are high.

[0005] The oxygen oxidation-selenium dioxide hydration method is currently the mainstream industrial route: selenium is oxidized with oxygen at high temperature (300-400℃) to generate selenium dioxide (SeO2) vapor, which is then purified by condensation and absorbed by deionized water to directly obtain a selenite solution. This solution is then concentrated, crystallized, and dried to obtain a solid product. This route can achieve high purity, but SeO2 is highly toxic, causes strong equipment corrosion, has high energy consumption at high temperatures, and a long production cycle. Furthermore, selenium has similar properties to associated impurities such as tellurium, lead, and arsenic, making deep separation difficult with conventional sublimation / distillation. This results in high levels of trace metal impurities such as tellurium, lead, and arsenic in the product, often leading to insufficient purity, excessive impurities, and poor stability in pharmaceutical applications.

[0006] Furthermore, the process of recovering crude selenium from rare and dispersed metal byproducts such as copper anode mud and then preparing selenite acid involves raw materials containing impurities such as copper, lead, tellurium, and silicon. Existing refining methods mostly employ simple acid dissolution, precipitation, and single crystallization, resulting in limited purification depth. Impurities are easily co-precipitated or encapsulated in the crystals, and the purity of the final product is mostly below 98%. It is difficult to stably control heavy metal and selenate impurities within pharmaceutical-grade limits (usually requiring single heavy metal <0.1ppm and total impurities <10ppm).

[0007] Relevant patent documents retrieved: This document, published in China (CN120622418A) on September 12, 2025, discloses a method for preparing selenite, including the following steps: S1. Preparation of crude product: Purified water is added to a reaction vessel, the reaction temperature is controlled at 50±60℃, selenium dioxide is added, the temperature is raised to 75-85℃, and the reaction is maintained for 2-4 hours. The mixture is filtered while hot. The filtrate is cooled to 40-45℃ at a rate of 10℃ / h, and stirred for 3 hours. After a large amount of solid precipitates, the temperature is further lowered to 0-10℃, stirred for 1 hour, and then filtered. The wet product is dried at room temperature at -0.09 MPa for approximately 3 hours. 5 hours. During the intermediate drying period of 2 hours, the material needs to be turned over once. Collect the crude selenite. S2. Decolorization and purification: Add purified water to the reactor, control the reaction temperature at 50±60℃, add the crude selenite, stir until dissolved, add pharmaceutical activated carbon, raise the temperature to 75-85℃, and maintain the temperature with stirring for about 2 hours. Filter while hot. Cool the filtrate to 40-45℃ and maintain the temperature with stirring for 3 hours. After a large amount of solid precipitates, continue cooling to 0-10℃, maintain the temperature with stirring for 1 hour, and then filter. Dry the wet product at room temperature and -0.09MPa for about 3-5 hours. During the intermediate drying period of 2 hours, the material needs to be turned over once. Collect the selenite.

[0008] Relevant non-patent literature retrieved: The journal is titled "Nonferrous Mining and Metallurgy," and the article titled "A New Process for Preparing Analytical Pure Selenite Acid" is in issue 1, published on February 28, 1999. This article discloses a method of mixing selenium dioxide with water at a ratio of 5:2-2.5, dissolving the mixture, filtering it, evaporating and crystallizing the filtrate, adding a small amount of hydrogen peroxide during crystallization (the amount of hydrogen peroxide added is determined by observing the color change of red selenium in the solution), concentrating the mixture at a temperature not exceeding 70°C, and determining the crystallization endpoint by observing the precipitation state of the product.

[0009] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: Patent document CN120622418A describes adding hydrogen peroxide by observing reaction phenomena to prevent selenite from decomposing into elemental selenium during the reaction and crystallization process. However, this method of observing reaction phenomena is not feasible for pharmaceutical raw material production and is unsuitable for industrial-scale production. Furthermore, hydrogen peroxide has strong oxidizing properties and can decompose some of the tetravalent selenium (Se) in selenite. 4+ ) oxidized to hexavalent selenium (Se) 6+ ) to form selenic acid.

[0010] To address this issue, the present invention employs the addition of a weak oxidizing agent, which ensures that elemental selenium is oxidized to tetravalent selenium without further oxidation to hexavalent selenium.

[0011] In addition, the post-processing in the existing technology uses high-temperature concentration and dehydration to obtain selenite acid. Since selenite acid is easily decomposed under high temperature conditions and the concentration and dehydration efficiency is low, resulting in serious energy waste, it is not suitable for large-scale industrial production.

[0012] Therefore, there is a need to find a preparation method that can remove most of the water and organic solvents during the filtration stage, so that the wet filter cake does not need to be dried at high temperature, thereby avoiding the degradation reaction of selenite acid at high temperature, and improving the purity of selenite acid so that the finished product meets pharmaceutical standards and is suitable for large-scale industrial production.

[0013] In solving the above problems or overcoming the above defects, the present invention encountered the following difficulties and obstacles: (1) Without the addition of an oxidizing agent, elemental selenium is produced during the reaction, and the solution changes from colorless to red.

[0014] (2) The wet product contains a large amount of free water. During the drying process, if the temperature is too low, the drying will be insufficient and the free water content will be too high; if the temperature is too high, the selenite will decompose and produce selenium dioxide and red selenium. Summary of the Invention

[0015] The purpose of this invention is to provide: A method for preparing selenite, and related technologies, to solve technical problems such as low purity and high product moisture content, or a combination thereof.

[0016] Terminology Explanation: Unless otherwise defined, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this subject matter pertains. Unless otherwise stated, all patents, patent inventions, and disclosures cited throughout this document are incorporated herein by reference in their entirety. Where multiple definitions exist for terms herein, the definitions provided in this chapter shall prevail.

[0017] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0018] Definitions of standard chemical terms can be found in the references "Inorganic Chemistry (6th Edition)" (Department of Inorganic Chemistry, Tianjin University, Higher Education Press, 2025) and "Chemical Engineering Principles" (Volumes 1 & 2, 5th Edition, Chemical Industry Press).

[0019] Unless otherwise stated, conventional methods within the scope of the art, such as carbon NMR spectroscopy, hydrogen NMR spectroscopy, ion chromatography, and gas chromatography, shall be used.

[0020] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0021] The “range” disclosed in this document takes the form of a lower limit and an upper limit. It can be one or more lower limits and one or more upper limits, respectively. A given range is defined by selecting a lower limit and an upper limit. The selected lower and upper limits define the boundaries of the particular range. All ranges that can be defined in this way are inclusive and composable; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is also expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if the minimum range values ​​are listed as 1 and 2, and if the maximum ranges are listed as 3, 4, and 5, then the following ranges are all expected: 1-2, 1-4, 1-5, 2-3, 2-4, and 2-5.

[0022] In this invention, unless otherwise specified, the numerical range "ab" represents a shortened representation of any combination of real numbers from a to b, where a and b are both real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" have been listed in this document, and "0-5" is simply a shortened representation of these numerical combinations.

[0023] The term "selenite" used in this article refers to an inorganic selenium-containing compound with the molecular formula H2SeO3. It is mostly a white crystalline solid at room temperature and is a commonly used selenium source. It can be prepared into pharmaceutical preparations such as injections and used as a selenium supplement for the human body.

[0024] The term "selenium dioxide" used in this article refers to selenium oxide with the molecular formula SeO2, which is a white crystalline powder at room temperature. It is easily sublimed, soluble in water, and forms selenite, making it an important intermediate product in the preparation of selenite.

[0025] The term "microporous filter membrane" as used in this article refers to a functional filter material with a uniform microporous structure at the micron level. It relies on sieving to trap solid particles and impurities in the solution and is often used for the precision purification, sterilization, and impurity removal of materials.

[0026] The term "filtration" as used in this article refers to a unit operation that uses porous media to intercept solid particles in a suspended system to achieve solid-liquid phase separation, and is used to remove insoluble impurities from materials.

[0027] The term "drying" as used in this article refers to the process of removing free moisture or residual solvent from solid materials through methods such as heating, ventilation, and depressurization to obtain a dried finished product.

[0028] The term "solvent removal" as used in this article refers to the conventional operation of evaporating or separating solvent molecules from a slurry, solution, or precursor system containing solvent through heating, depressurization, negative pressure, or forced air, thereby achieving system concentration or drying. This includes, but is not limited to, heating evaporation, depressurization evaporation, vacuum drying, spray drying, depressurization drying, atmospheric pressure drying, and rotary evaporation.

[0029] The term "solvent removal" as used in this article refers to the operation of separating and removing liquid components such as water and organic solvents from the material by means of evaporation, depressurization, distillation, etc.

[0030] The term "wet filter cake" as used in this article refers to the solid filter cake layer containing residual solvent or moisture that remains on the surface of the filter medium after the material has been filtered and separated.

[0031] The term "degradation reaction" used in this article refers to a chemical reaction in which the molecular structure of a substance is destroyed and decomposed under the influence of factors such as chemical environment, temperature, and impurities, generating other byproducts.

[0032] The term “trace element (selenium) supplement” as used in this article refers to: medicines, preparations or functional products that use selenium as the active ingredient to supplement the human body’s need for the essential trace element selenium and to prevent or improve selenium deficiency-related conditions.

[0033] The term "evaporation crystallization" as used in this article refers to an integrated process in which the solvent in an evaporation system is heated to achieve a supersaturated state, thereby precipitating crystals.

[0034] The term "crystallization" as used in this article refers to the phase transition and separation process in which a solute precipitates from a supersaturated solution to form a solid crystal with a regular geometric shape.

[0035] The term "concentration" as used in this article refers to a process operation that increases the concentration of solute in a solution by reducing the solvent content, often used as a pre-process step in crystallization, refining, and other similar procedures.

[0036] The term "oxidizing property" used in this article refers to the chemical property of a substance that can take electrons from other substances, causing the other substance to undergo an oxidation reaction, while the substance itself is reduced.

[0037] The term "oxidizing agent" as used in this article refers to a chemical substance that has oxidizing properties in chemical reactions, can gain electrons, reduce its oxidation state, and promote the oxidation of other substances.

[0038] The term "selenic acid" used in this article refers to a high-valence selenium inorganic acid with the molecular formula H2SeO4, which is an oxidation product of selenite. The two have significantly different chemical properties and applications.

[0039] The term "stirring" as used in this article refers to the operation of mixing a system with the aid of a stirring device to achieve uniform contact of materials, heat and mass transfer, and to ensure the stable progress of the reaction or mass transfer process.

[0040] The term "crystal" as used in this article refers to a solid substance with a fixed melting point and regular shape, whose internal particles are arranged in a periodic and orderly manner according to certain rules.

[0041] In a first aspect, the present invention provides: a method for preparing selenite, comprising the steps of: (1) Selenium dioxide is mixed with water, and an oxidant is added and stirred to react to obtain crude product; (2) Filter the crude product obtained in step (1), add organic solvent to the filtrate to crystallize, and obtain the product after removing the solvent.

[0042] Wherein, the mass ratio of selenium dioxide to water in step (1) is 1.0:0.5-1.2, for example 1.0:0.5, 1.0:0.6, 1.0:0.7, 1.0:0.8, 1.0:0.9, 1.0:1.0, 1.0:1.1, 1.0:1.2, or any range derived thereof; Preferably, the mass ratio of selenium dioxide to water in step (1) is 1.0:1.0.

[0043] The mixing temperature in step (1) is 40-50℃, for example 40℃, 41℃, 42℃, 43℃, 44℃, 45℃, 46℃, 47℃, 48℃, 49℃, 50℃, or any range derived therefrom.

[0044] Wherein, the oxidant mentioned in step (1) is a weak oxidant; Further, the oxidant in step (1) is at least one of ferric chloride, sodium bisulfite, and sodium sulfite; Furthermore, the oxidant in step (1) is ferric chloride.

[0045] Wherein, the amount of oxidant added in step (1) is 0.5%-3% of the mass of selenium dioxide, for example 0.5%, 0.7%, 0.9%, 1.1%, 1.3%, 1.5%, 1.7%, 1.9%, 2.1%, 2.3%, 2.5%, 2.7%, 2.9%, 3%, or any range derived therefrom; Preferably, the amount of oxidant added in step (1) is 1.46% of the mass of selenium dioxide.

[0046] The duration of the stirring reaction in step (1) is 20-60 min, for example 20 min, 22 min, 24 min, 26 min, 28 min, 30 min, 32 min, 34 min, 36 min, 38 min, 40 min, 42 min, 44 min, 46 min, 48 min, 50 min, 52 min, 54 min, 56 min, 58 min, 60 min, or any range derived therefrom; Furthermore, the stirring reaction in step (1) lasts for 30 minutes.

[0047] Among them, the filtration method described in step (2) is microporous membrane filtration; Furthermore, the filter membrane size of the microporous filter membrane is selected from 0.22μm, 0.45μm or 0.8μm.

[0048] In step (2), the organic solvent is acetonitrile.

[0049] Wherein, the crystallization temperature in step (2) is 0-10℃, for example 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, or any range derived therefrom; Furthermore, the crystallization temperature in step (2) is preferably 5°C.

[0050] The crystallization time in step (2) is 3-5 hours, for example, 3 hours, 3.2 hours, 3.4 hours, 3.6 hours, 3.8 hours, 4.0 hours, 4.2 hours, 4.4 hours, 4.6 hours, 4.8 hours, 5.0 hours, or any range derived therefrom. Furthermore, the crystallization temperature in step (2) is preferably 4 h.

[0051] In some specific embodiments, step (2) further includes a rinsing step after the crystallization process.

[0052] The solvent used for rinsing is acetonitrile.

[0053] In step (2), the solvent removal method is vacuum drying.

[0054] Preferably, the drying temperature is selected from 35-45℃, for example 35℃, 36℃, 37℃, 38℃, 39℃, 40℃, 41℃, 42℃, 43℃, 44℃, 45℃, or any range derived therefrom; More preferably, the drying temperature is 40°C.

[0055] Preferably, the drying time is selected from 4-5h, for example 4.0h, 4.1h, 4.2h, 4.3h, 4.4h, 4.5h, 4.6h, 4.7h, 4.8h, 4.9h, 5.0h, or any range derived therefrom.

[0056] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the first aspect of the present invention includes: The first preferred solution is that the mass ratio of selenium dioxide to water in step (1) is 1.0:0.5-1.2; preferably 1.0:1.0. This technical solution not only solves the technical problem of "increasing yield and reducing moisture content", but also further solves the technical problem of "improving product purity".

[0057] The second preferred option is that the oxidant is at least one of ferric chloride, sodium bisulfite, and sodium sulfite; preferably ferric chloride. This technical solution, while addressing the technical problems of "increasing yield and improving product purity," further solves the technical problem of "reducing moisture content."

[0058] Secondly, the present invention provides the application of the preparation method in pharmaceutical preparations, metallurgical surface treatment, feed additives, and analytical testing.

[0059] The pharmaceutical applications mentioned above are as follows: High-purity selenite (purity ≥99.5%) is the core raw material for preparing selenite injection, various trace element injections and organic selenium drugs (such as selenium ethyl ether), and is used for human selenium supplementation and adjuvant treatment of related diseases.

[0060] The applications in metallurgical surface treatment include: using selenite for room temperature bluing (cold bluing) of steel, coloring and anti-corrosion treatment of copper / brass / bronze, forming a stable selenide protective film.

[0061] The application in feed additives is as follows: selenite and its salts are used as highly efficient selenium supplements in feed additives and selenium-enriched fertilizers to enhance animal immunity and crop selenium content.

[0062] The application in analysis and detection is as follows: selenite is used as a spectral analysis reagent, alkaloid precipitant and Mecke reagent component for rapid screening of metal ions.

[0063] The term "oxidizing agent" is derived from the foregoing explanation and / or from "ferric chloride" in Example 1, "NaHSO3" in Example 5, and "Na2SO3" in Example 8, etc. Therefore, those skilled in the art can reasonably infer that "oxidizing agent," its subordinate concepts, its substantially equivalent technical means, and technical means that can replace it within the scope of conventional technical means and common knowledge based on the existing level of technology should all fall within the protection scope of this invention.

[0064] The phrase "the mass ratio of selenium dioxide to water is 1.0:0.5-1.2" is a generalization derived from the foregoing explanation and / or the "1.0:1.0" in Example 1, "1.0:0.5" in Example 3, and "1.0:1.2" in Example 7. Therefore, those skilled in the art can reasonably infer that "the mass ratio of selenium dioxide to water is 1.0:0.5-1.2," its subordinate concepts, its essentially equivalent technical means, and technical means that can replace it within the scope of conventional and common knowledge based on the existing level of technology should all fall within the protection scope of this invention.

[0065] The application of "in pharmaceutical preparations, metallurgical surface treatment, feed additives, and analytical testing" is summarized from the foregoing explanation and / or the corresponding technical features in Examples 1-8: "The application in pharmaceutical preparations is that high-purity selenite (purity ≥99.5%) is the core raw material for preparing selenite injections, various trace element injections, and organic selenium drugs (such as selenium ethylhexene), used for human selenium supplementation and adjuvant treatment of related diseases," and "The application in metallurgical surface treatment is that selenite is used for room-temperature bluing (cold bluing) of steel, coloring and anti-corrosion treatment of copper / brass / bronze, forming a stable selenide protective film." Therefore, those skilled in the art can reasonably presume that "the application in pharmaceutical preparations, metallurgical surface treatment, feed additives, and analytical testing," its subordinate concepts, its essentially equivalent technical means, and technical means that can replace it within the scope of conventional technical means and common knowledge based on the existing technical level should all fall within the protection scope of this invention.

[0066] The beneficial effects of this invention are as follows: The present invention has at least the following beneficial effects: (1) In this invention, a weak oxidizing agent is added so that the elemental selenium is oxidized to tetravalent selenium and will not continue to be oxidized to hexavalent selenium.

[0067] (2) This method can remove most of the water and organic solvents during the filtration stage, so that the wet filter cake does not need to be dried at high temperature, thereby avoiding the degradation reaction of selenite acid at high temperature, improving the purity of selenite acid, making the finished product meet pharmaceutical standards, and suitable for large-scale industrial production.

[0068] (3) Compared with the prior art, the present invention has better technical effects in terms of selenite content, water insoluble matter, selenium dioxide, and elemental selenium.

[0069] According to experimental tests, the present invention increases the selenite content from 96% in the prior art to over 99%.

[0070] According to experimental tests, the present invention reduces the water-insoluble content of selenite from "less than 1%" in the prior art to below 0.5%.

[0071] According to experimental tests, the present invention reduces the selenium dioxide content in selenite from 2.4% in the prior art to below 0.3%.

[0072] According to experimental tests, the present invention reduces the selenium content in selenite from 0.7% in the prior art to below 0.15%.

[0073] (4) Compared with the prior art, the present invention provides a technical solution with a different technical concept, and its technical effect is equivalent to or slightly improved with the prior art. The difference between the technical concept of the present invention and the prior art includes, but is not limited to, reaction temperature, crystallization method, drying method, etc.

[0074] Furthermore, based on the present invention: 1. Based on the comparison of Example 1 and Comparative Examples 3-4, the present invention purposefully selects "ferric chloride, sodium bisulfite, and sodium sulfite" from the wide range of oxidant types disclosed in the prior art, which are not mentioned in the prior art, and achieves unexpected technical effects such as significantly reducing moisture content, improving product purity and yield. Attached Figure Description

[0075] Figure 1 This is a flow chart of the selenite production process.

[0076] Figure 2 The infrared (IR) spectrum of selenite obtained in Example 2 of this application is shown.

[0077] Figure 3 The XRD pattern is that of the selenite obtained in Example 2 of this application. Detailed Implementation

[0078] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0079] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0080] Specific raw material information is shown in Table 1: Table 1. Raw Material Information

[0081] In the following embodiments, the detection method / calculation method is as follows: (1) Moisture content: Moisture content was determined by vacuum drying: 2g of the product was accurately weighed, dried at 105℃, and the moisture content was determined according to the method for moisture determination (Chinese Pharmacopoeia 2025 Edition, Part IV, General Chapter 0832, Method II).

[0082] (2) Selenite content: The selenite content was determined by titration: 100 mg of the sample was accurately weighed and placed in an iodine flask. 100 mL of water was added to dissolve the sample, followed by 5 mL of hydrochloric acid and 10 mL of chloroform. The mixture was then titrated with 0.1 mol / L sodium thiosulfate until near the endpoint. 2 g of potassium iodide was added, the flask was sealed tightly, and the solution was shaken well. The solution was placed in the dark for 5 minutes. 4 mL of starch indicator solution was added, and the solution was titrated until the layers separated. The mixture was then shaken vigorously for 1 minute, and titrated until the lower layer's purple-red color disappeared. Each 1 mL of 0.1 mol / L sodium thiosulfate titrant is equivalent to 3.225 mg of H₂SeO₃.

[0083] Calculation formula

[0084] T: Titration value of the titrant, mg / mL; V 样 : Volume of titrant consumed, mL; W 供 Sample size, mg; F: is the titrant concentration correction factor, F = actual titrant concentration / specified titrant concentration.

[0085] (3) Yield: Yield calculation formula:

[0086] M1: Selenium dioxide feed amount; 110.96: Molecular weight of selenium dioxide; M2: Selenite production; 128.97: Molecular weight of selenite.

[0087] (4) Insoluble matter in water: Test method for insoluble matter in water: Weigh 1g of this product accurately, add 5mL of water to dissolve it completely, and the solution should be clear (Chinese Pharmacopoeia 2025 Edition, Part IV, General Chapter 0902, Method I).

[0088] (5) Selenium dioxide: The selenium dioxide content was determined by spectroscopic analysis and chemical imaging technology (Chinese Pharmacopoeia 2025 Edition, Part IV, General Chapter 9031).

[0089] (6) Selenium The determination of selenium was performed according to the inductively coupled plasma atomic emission spectrometry method (Chinese Pharmacopoeia 2025 Edition, Part IV, General Chapter 0411).

[0090] Example 1 Selenium dioxide (30 g, 0.27 mol) was added to 30 mL of purified water and stirred at 45 °C until completely dissolved. Ferric chloride (0.44 g, 0.003 mol) was added, and the mixture was kept at this temperature for 30 minutes. The solution was filtered through a microporous membrane, and the filtrate was slowly added dropwise to 180 mL of acetonitrile. The mixture was cooled to 5 °C and allowed to crystallize for 3 hours. After filtration, the filtrate was washed with 30 mL of anhydrous ethanol, and the filter cake was collected and dried under reduced pressure at 40 °C for 4 hours to obtain 32.44 g of white crystals (selenite).

[0091] The test results showed that the product contained 0.12% moisture, 99.97% selenite, and had a yield of 93.03%. The amount of water-insoluble matter was less than 0.5%, and neither selenium dioxide nor elemental selenium was detected.

[0092] Example 2 Selenium dioxide (1.5 kg, 13.5 mol) was added to 1.5 L of purified water and stirred at 45 °C until completely dissolved. Ferric chloride (21.9 g, 0.135 mol) was added, and the reaction was maintained at this temperature for 30 minutes. The mixture was then filtered through a microporous membrane, and the filtrate was slowly added dropwise to 9 L of acetonitrile. The mixture was cooled to 5 °C and allowed to crystallize for 4 hours. After filtration, the filtrate was washed with 1.5 L of acetonitrile, and the filter cake was collected and dried under reduced pressure at 40 °C for 5 hours to obtain 1674 g of white crystals (selenite).

[0093] The test results showed that the product contained 0.11% moisture, 99.98% selenite, and had a yield of 96.01%. Selenium dioxide and elemental selenium were not detected.

[0094] Compared with Example 1, Examples 3-8 only changed some process conditions; the overall preparation steps were essentially the same as in Example 1. The specific process parameters and experimental results of Examples 3-8 are shown in the table below: Table 2

[0095] Comparative Example 1 The preparation of selenite was carried out according to the preparation scheme described in the literature titled "A New Process for Preparing Analytical Grade Selenite Acid". The resulting product had a moisture content of 1.2%, a selenite content of 93.67%, a yield of 84.6%, a selenium dioxide content of 1.4%, and a selenium content of 0.9%. Comparative Example 2 Compared with Example 1, the only difference is that the mass ratio of selenium dioxide to purified water is replaced with "1.0:1.5", and all other conditions are basically the same as in Example 1.

[0096] The test results showed that the product had a moisture content of 1.1%, a selenite content of 99.87%, a yield of 63.7%, a selenium dioxide content of <0.13%, and a selenium content of <0.15%.

[0097] Comparative Example 3 Compared with Example 1, the only difference is that the oxidant is replaced with hydrogen peroxide, while the other conditions are basically the same as in Example 1.

[0098] The test results showed that the product had a moisture content of 1.0%, a selenite content of 97.46%, a yield of 92.3%, a selenium dioxide content of <0.13%, and a selenium content of <0.15%.

[0099] Comparative Example 4 Compared with Example 1, the only difference is that the oxidant is replaced with peracetic acid, while the other conditions are basically the same as in Example 1.

[0100] The test results showed that the product had a moisture content of 1.4%, a selenite content of 88.32%, a yield of 75.4%, a selenium dioxide content of <0.13%, and a selenium content of <0.15%.

[0101] Verification of technical effectiveness and / or analysis of technical problem solving A comparative experiment was conducted in conjunction with Examples 1-8 and Comparative Examples 1-4 to verify the technical effectiveness of this solution from the dimensions of product moisture, selenite content, yield, selenium dioxide and elemental selenium residue, and to analyze the problems existing in the prior art.

[0102] Traditional processing methods result in selenite acid products with high moisture content, which can negatively impact storage and usage stability. This solution optimizes drying and post-processing steps, effectively removing moisture from the material and achieving better dryness, thus improving product stability. Selenite content is a core indicator of product quality. Existing processes suffer from poor oxidant selectivity and limited impurity removal capabilities, making it difficult to achieve pharmaceutical-grade purity. This solution selects a suitable oxidant and employs temperature control, stepwise crystallization, and precision filtration to ensure targeted conversion of raw materials while effectively removing various impurities, significantly increasing the selenite content and meeting the purity requirements for pharmaceutical raw materials.

[0103] Traditional processes suffer from insufficient raw material conversion and significant product loss in post-processing, resulting in low overall yield. This proposed solution optimizes various process parameters, improves raw material conversion, and reduces product loss during separation and purification, leading to a significant increase in product yield and enhanced process economics.

[0104] Selenium dioxide, as an intermediate product, is toxic, and elemental selenium is an insoluble impurity; both are key controlled substances for pharmaceutical raw materials. Existing processes suffer from incomplete reactions and limited impurity removal methods, easily leading to excessive residues of these two substances. This proposed solution optimizes reaction conditions to promote complete conversion of the intermediate and combines this with staged filtration to remove solid impurities, significantly reducing the residual amounts of selenium dioxide and elemental selenium, thus ensuring the safety of raw material use.

[0105] In summary, this process has significant advantages over existing technologies, effectively solving problems such as low purity, high impurity content, poor yield, and poor stability of traditional products. The resulting product meets the usage requirements of pharmaceutical applications in all aspects.

[0106] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing selenite, characterized in that, Including the following steps: (1) Selenium dioxide is mixed with water, and an oxidant is added and stirred to react to obtain crude product; (2) Filter the crude product obtained in step (1), add organic solvent to the filtrate to crystallize, and obtain the product after removing the solvent; The oxidant in step (1) is at least one of ferric chloride, sodium bisulfite, and sodium sulfite.

2. The preparation method according to claim 1, characterized in that, The mass ratio of selenium dioxide to water in step (1) is 1.0:0.5-1.

2.

3. The preparation method according to claim 1, characterized in that, The mixing temperature in step (1) is 40-50℃.

4. The preparation method according to claim 1, characterized in that, The amount of oxidant added in step (1) is 0.5%-3% of the mass of selenium dioxide.

5. The preparation method according to claim 1, characterized in that, The stirring reaction in step (1) lasts for 20-60 minutes.

6. The preparation method according to claim 1, characterized in that, The filtration method described in step (2) is microporous membrane filtration; The organic solvent in step (2) is acetonitrile.

7. The preparation method according to claim 1, characterized in that, The crystallization temperature in step (2) is 0-10℃; the crystallization time in step (2) is 3-5h.

8. The preparation method according to claim 1, characterized in that, Step (2) further includes a rinsing step after the crystallization process.

9. The preparation method according to claim 1, characterized in that, The solvent removal method in step (2) is vacuum drying; The temperature for vacuum drying is selected from 35-45℃, and the time for vacuum drying is selected from 4-5h.

10. The application of the preparation method according to any one of claims 1-9 in pharmaceutical preparations, metallurgical surface treatment, feed additives, and analytical testing.

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