A preparation process for pharmaceutical grade isopropyl alcohol

Abstract

The present invention provides a preparation process for pharmaceutical-grade isopropyl alcohol, and relates to the technical field of isopropyl alcohol purification. The process comprises the following steps: using analytically pure isopropyl alcohol as a raw material, adding potassium borohydride and hydroxide at a solid-to-liquid ratio of 6 to 8:1000, and mixing uniformly; subjecting the mixture to reflux reaction at 80 to 85°C for 3 to 5 hours; performing atmospheric distillation with a top temperature controlled at 82.3 to 82.7°C, and collecting the intermediate fraction; testing the intermediate fraction, and obtaining pharmaceutical-grade isopropyl alcohol if it meets the standards; in step S100, adding the hydroxide in stages: adding potassium borohydride and 45% to 55% of the hydroxide simultaneously to the isopropyl alcohol, and reflux reaction for 1.0 to 1.2 hours; and slowly adding the remaining hydroxide in the form of solid powder, controlling the addition rate to be ≤0.5 g / min. The present invention significantly improves the impurity removal efficiency through processes such as staged alkali addition, coordinated reduction of potassium borohydride and hydroxide, and precise distillation control: the carbonyl compound content is reduced to 0.5 ppm; the pass rate of potassium permanganate oxidation test is increased to 100%; and the absorbance at 230 nm is reduced to ≤0.08.

Description

Technical Field

[0001] The invention relates to the technical field of isopropyl alcohol purification, and in particular to a preparation process of pharmaceutical-grade isopropyl alcohol. Background Art

[0002] Isopropyl alcohol (IPA), an important organic solvent and pharmaceutical excipient, is widely used in injections, topical solutions, and medical device disinfection. Pharmacopoeia-grade IPA must meet stringent quality standards, such as those stipulated in the 2020 edition of the Chinese Pharmacopoeia: moisture ≤ 0.2%, UV absorbance (230 nm) ≤ 0.3, and must pass the potassium permanganate oxidation test (oxidizable substances test). However, traditional purification processes face the following technical bottlenecks:

[0003] Limitations of distillation: Industrial-grade isopropyl alcohol is often produced using multi-stage distillation to remove light components (methanol, acetone) and heavy components (higher alcohols). However, carbonyl compounds (such as residual acetone) are difficult to completely separate due to their similar boiling points to isopropyl alcohol (acetone 56.5°C vs. isopropyl alcohol 82.5°C), requiring additional adsorption treatment.

[0004] Disadvantages of adsorption: Activated carbon or ion exchange resins are used to adsorb impurities, but there are two major problems:

[0005] Poor selectivity: The adsorption rate of activated carbon for benzene series (such as toluene) is greater than 90%, but the adsorption rate for small molecular carbonyl compounds (such as formaldehyde) is less than 50%; risk of secondary pollution: resin breakage or activated carbon powder may introduce non-volatile matter (exceeding the standard to 0.003%), requiring additional filtration steps, which complicates the process.

[0006] Challenges of redox methods: Some processes attempt to degrade impurities through oxidation (such as ozone treatment) or reduction (such as NaBH4), but there are difficulties in reaction control: the pH of the NaBH4 system must be strictly controlled (8-9) to prevent the isopropanol itself from being reduced, and residual borate (≤0.001%) is difficult to completely remove; although ozone oxidation can decompose benzene series compounds, it will produce aldehyde byproducts (such as formaldehyde), which will lead to an increase in the content of carbonyl compounds (0.007%-0.01%).

[0007] UV absorbance control challenges: Pharmacopoeia-grade isopropyl alcohol requires an absorbance of ≤0.3 at 230 nm. However, trace amounts of conjugated olefins (such as isopropyl ether oxidation products) or aromatic impurities (such as benzene series) can cause absorbance to exceed the standard. Existing technologies use photocatalytic degradation, but this requires high equipment investment (a UV reactor is required) and may trigger photolysis of the isopropyl alcohol (generating acetone, which in turn increases the carbonyl content).

[0008] Existing processes either rely on high-energy distillation or face the risk of incomplete impurity removal and secondary pollution, making it difficult to meet the "low impurity, low absorbance, and high stability" requirements of pharmaceutical-grade isopropyl alcohol. Summary of the Invention

[0009] The invention provides a preparation process of pharmaceutical-grade isopropyl alcohol. The process comprises the following steps: reducing analytical-grade isopropyl alcohol with borohydride and hydroxide, and then distilling and purifying the isopropyl alcohol by atmospheric distillation to obtain pharmaceutical-grade isopropyl alcohol with low impurities, low absorbance and high stability.

[0010] A preparation process for pharmaceutical-grade isopropyl alcohol comprises the following steps:

[0011] S100, using analytical grade isopropyl alcohol as the raw material, adding potassium borohydride and hydroxide at a solid-liquid ratio of 6-8:1000, and mixing well;

[0012] S200, reflux the mixture at 83-85° C. for 3-5 hours;

[0013] S300, atmospheric distillation, controlling the top temperature at 82.3-82.7°C, discarding the front fraction, and collecting the middle fraction; S400, testing the middle fraction, and obtaining pharmaceutical-grade isopropyl alcohol after it meets the standards;

[0014] In step S100, the hydroxide is added in stages, including: the first stage: 45% to 55% by mass of hydroxide and potassium borohydride are added to isopropanol at the same time, and a reflux reaction is started for 1.0 to 1.2 hours; the second stage: the remaining hydroxide is slowly added in the form of solid powder, and the addition rate is controlled to be ≤0.5 g / min; the hydroxide includes sodium hydroxide.

[0015] By adding hydroxide in stages (synergistically with potassium borohydride (KBH4), the carbonyl compound content was reduced to ≤0.002%. In the first stage (45%-55% by mass hydroxide), the initial alkaline environment activated the reducing activity of KBH4, selectively reducing carbonyl impurities in the feedstock (e.g., acetone to isopropanol). In the second stage (residual hydroxide), alkalinity was added to maintain a pH ≥ 12, decomposing residual oxidizable substances (e.g., peroxides) and ensuring 100% compliance with the potassium permanganate test. UV absorbance control: The absorbance at 230 nm was reduced from 0.3-0.5 (of the feedstock) to ≤0.08, and the absorbance at 250-310 nm was significantly reduced, indicating efficient removal of conjugated olefins and aromatic impurities. Staged addition avoided localized strong base, minimizing the dehydration of isopropanol to acetone (side reaction inhibition rate ≥80%). Precise distillation head temperature (82.3-82.7°C) effectively separated light components (methanol, water) from heavy components (polymers, metal complexes).

[0016] Traditional processes use a single-step addition, which can easily lead to localized strong base-induced isopropyl alcohol dehydration reactions, producing acetone. This present invention uses a phased addition of hydroxide: 45% to 55% in the first phase, followed by the remainder in the second phase. This keeps pH fluctuations within ±0.5 and reduces byproduct formation by 80%. The first phase reacts for 1.0 to 1.2 hours: the initial alkaline environment activates the reducing activity of KBH₄, preferentially degrading easily oxidized substances. In the second phase, the solid powder is added at a low rate to avoid excessive heat release and maintain system stability (temperature fluctuations ≤ ±1°C). Traditional processes rely on a single reducing agent (such as NaBH₄), requiring the addition of a stabilizer (such as ethylenediamine) to prevent self-decomposition. This present invention innovatively utilizes a KBH₄ / NaOH combination, leveraging potassium ions to enhance the solubility of BH₄⁻, achieving a 25% improvement in reduction efficiency without auxiliary reagents. The present invention maintains a pH of 12 or higher through staged alkali addition, thereby increasing the pass rate of potassium permanganate oxidation tests from 70% to 100%. The reduction system selectively degrades conjugated impurities, reducing the absorbance at 230 nm from 0.489 to 0.08. The invention also combines inorganic reduction chemistry (KBH4) with precision distillation, breaking through the single-dimensional limitations of traditional purification processes (adsorption and distillation), achieving the dual goals of impurity removal and product stability, and enabling the efficient and low-cost preparation of pharmaceutical-grade isopropyl alcohol.

[0017] Sodium hydroxide is preferably used as the hydroxide. NaOH has strong alkalinity and is more conducive to maintaining the pH of the reaction system ≥ 12, ensuring the continuous release of BH4⁻. The price of NaOH is significantly lower than that of KOH, which reduces the process cost. NaOH has a moderate solubility in isopropanol (about 5 g / 100 mL), which can avoid crystallization or agglomeration caused by local oversaturation.

[0018] Furthermore, in step S100, the mass ratio of potassium borohydride to hydroxide is 1:0.8-1.1.

[0019] KBH4 decomposes under alkaline conditions to generate active BH4⁻ ions, which selectively reduce carbonyl compounds (such as acetone) in isopropanol to alcohols (isopropanol); hydroxide provides an alkaline environment (pH ≥ 12) to promote the release of BH4⁻; and neutralizes the acidic byproducts (such as B(OH)3) generated by the reaction to prevent the system from becoming acidic and causing a decrease in reduction efficiency.

[0020] The mass ratio of potassium borohydride to hydroxide is 1:0.8~1.1 to avoid side reactions caused by excess base: Excess NaOH may catalyze the dehydration of isopropanol. When the mass ratio is greater than 1:1.1, the acetone content in the system increases significantly. At the same time, excess NaOH accelerates the hydrolysis of KBH4 (2KBH4+2H2O→2KOH+B2H6↑+2H2↑), reducing the reduction efficiency.

[0021] Furthermore, in the first stage, the temperature is 80-85° C., sodium hydroxide and potassium borohydride are dry-mixed and then added to isopropyl alcohol, and the particle size of the sodium hydroxide is 100-200 mesh.

[0022] The decomposition rate of KBH4 increases significantly at 80-85°C, releasing active BH4⁻ ions and rapidly reducing carbonyl compounds (such as acetone → isopropanol). Dry mixing can reduce the introduction of moisture: preventing KBH4 from reacting with water prematurely (2KBH4+2H2O→ 2KOH+B2H6↑+2H2↑), reducing hydrogen generation, and lowering the risk of explosive boiling; solid powder mixing ensures that NaOH and KBH4 are evenly distributed in isopropanol, avoiding local excessive pH that causes dehydration of isopropanol (generating acetone).

[0023] Furthermore, when sodium hydroxide is added in the second stage, the reaction temperature is reduced to 70-75°C. After the addition is completed, the temperature is raised to 80-83°C at a rate of 0.5-1.0°C / min to continue the reaction.

[0024] The purpose of adding NaOH by cooling is to: suppress violent exotherm: NaOH dissolves and reacts with KBH4 to release heat. Cooling to 70-75°C can slow down the reaction rate and prevent a sudden temperature rise (ΔT>5°C) that may lead to dehydration of isopropanol or excessive decomposition of KBH4; accurately control the pH gradient: NaOH is added in stages to maintain the system pH ≥ 12, avoid a local strong alkaline environment (pH> 13) caused by a one-time addition, and reduce the formation of by-products.

[0025] The effect of slow heating (0.5-1.0°C / min): After heating to 80-83°C, the remaining carbonyl compounds are further reduced, and the activation energy of the reaction is reduced; it effectively inhibits side reactions and avoids dehydration of isopropanol caused by sudden temperature changes.

[0026] Furthermore, in step S100, the hydroxide further includes potassium hydroxide, and the molar ratio of potassium hydroxide to sodium hydroxide is 1:3-5.

[0027] The synergistic mechanism of potassium hydroxide and sodium hydroxide:

[0028] Functions of KOH: Promote the ionization of BH4⁻: K⁺ ions form more stable ion pairs with BH4⁻ (K⁺···BH4⁻), improve the solubility and reactivity of potassium borohydride in isopropanol, and accelerate the reduction of carbonyl compounds; Inhibit the self-decomposition of KBH4: K⁺ can partially replace Na⁺ to bind to BH4⁻, slowing down the hydrolysis rate of KBH4 under alkaline conditions (compared with the pure NaOH system, the residual KBH4 is reduced by 50%).

[0029] The dominant role of NaOH: maintaining a high pH environment (pH ≥ 12): NaOH is more alkaline, ensuring the continuous release of BH4⁻; neutralizing by-products: the boric acid (B(OH)3) generated by the reaction is neutralized by NaOH to prevent the system from acidifying. The reaction equation is: B(OH)3+NaOH→NaBO2+2H2O.

[0030] When the molar ratio of potassium hydroxide to sodium hydroxide is greater than 1:3, excess NaOH may lead to dehydration of isopropanol (acetone production increases to 0.003%); when the molar ratio is less than 1:5, KOH is insufficient, BH4⁻ is not fully ionized, and the reduction efficiency decreases.

[0031] K⁺ ions can increase the solubility and reactivity of BH4⁻, increasing the removal rate of carbonyl compounds to 99%; the mixed alkali residue is ≤10 ppm, which can inhibit the growth of microorganisms during the storage of pharmaceutical excipients.

[0032] Furthermore, the particle size of the potassium hydroxide is ≤200 mesh, and the potassium hydroxide is added 5 to 10 minutes before the potassium borohydride is added.

[0033] KOH is added 5 to 10 minutes before potassium borohydride to pre-neutralize trace acidic impurities (such as acetic acid) in the raw material isopropanol, avoiding consumption of subsequently added KBH4.

[0034] Furthermore, in step S200, the reflux reaction temperature is 81-83°C, the reaction time is 3.8-4.2 hours, and the pH of the reaction system is ≥12.

[0035] Furthermore, in step S300, the amount of the discarded front fraction is 5% to 8% of the raw material volume; the volume of the collected middle fraction is 85% to 90% of the raw material volume; the kettle residue accounts for ≤10%, and the kettle temperature is 95 to 105°C.

[0036] A thorn-shaped fractionating column (number of plates ≥ 10) is used to enhance the separation effect and reduce the carryover of light and heavy components; the temperature difference (12.5~22.5℃) between the top temperature (82.5℃) and the kettle temperature (95~105℃) is achieved through the fractionating column to achieve gas-liquid equilibrium and ensure efficient separation.

[0037] Furthermore, the detection includes ultraviolet absorbance detection and potassium permanganate oxidation detection.

[0038] Furthermore, the wavelength range of the ultraviolet light is 230~310nm.

[0039] 230 nm: Detects conjugated double bonds, such as olefins produced by oxidation of isopropanol; 250-310 nm: Monitors aromatic impurities, such as benzene series.

[0040] Advantageous Effects of the Invention

[0041] This method significantly improves impurity removal efficiency through phased base addition, coordinated reduction with potassium borohydride (KBH4) and hydroxide (NaOH / KOH), and precise distillation control. The content of carbonyl compounds (such as acetone) is reduced from 0.0027% of the raw material to 0.5 ppm. The potassium permanganate oxidation test pass rate for easily oxidizable substances (reducible impurities) is increased from 70% to 100%. The UV absorbance at 230 nm is reduced from 0.3-0.5 to ≤0.08, and conjugated impurities are reduced by 90%. Precision distillation, with a top temperature of 82.3-82.7°C, reduces fore-fractions and still residue, and increases isopropyl alcohol recovery by 8-10%. This preparation process requires no additional dehydration or adsorption steps, eliminates the introduction of organic solvents, and allows the recovery of boron (such as borax) from the still residue, effectively reducing hazardous waste emissions.

[0042] UV absorbance testing quantitatively assesses the content of conjugated olefins, aromatic compounds (such as benzene), and other UV-active impurities in isopropyl alcohol by measuring the light absorption intensity at specific wavelengths (230-310 nm). Absorbance directly reflects impurity concentration and is a key indicator in pharmacopoeias. DETAILED DESCRIPTION

[0043] Example 1

[0044] A preparation process for pharmaceutical-grade isopropyl alcohol comprises the following steps:

[0045] S100. Using 1000 ml of analytical grade isopropanol as the raw material, in the first stage, 0.9 g of potassium hydroxide powder with a particle size of 100 mesh was added at a temperature of 82.5° C. After 8 minutes, 3.5 g of potassium borohydride and 1.3 g of sodium hydroxide with a particle size of 150 mesh were dry-mixed and added to the isopropanol, and a reflux reaction was initiated for 1.0 hour. In the second stage, the reaction temperature was lowered to 73° C., and the remaining 1.3 g of sodium hydroxide was slowly added in the form of solid powder at a control rate of 0.4 g / min. After mixing evenly, the temperature was raised to 82° C. at a rate of 0.8° C. / min to continue the reaction.

[0046] The mass ratio of potassium borohydride to hydroxide is 1:1; the molar ratio of potassium hydroxide to sodium hydroxide is 1:4.

[0047] S200, reflux the mixture at 84° C. for 4 hours.

[0048] S300: Perform atmospheric distillation, controlling the top temperature at 82.5°C, discard the front fraction, and collect the middle fraction; the discarded front fraction is 7% of the raw material volume; the collected middle fraction is 88% of the raw material volume; the kettle residue accounts for 5%, and the kettle temperature is controlled at 100°C. S400: Perform UV absorbance and potassium permanganate oxidation tests on the middle fraction. If it meets the standards, pharmaceutical-grade isopropyl alcohol is obtained.

[0049] Example 2

[0050] A preparation process for pharmaceutical-grade isopropyl alcohol comprises the following steps:

[0051] S100. Using 1000 ml of analytical grade isopropanol as the raw material, in the first stage, at a temperature of 85°C, add 0.86 g of potassium hydroxide powder with a particle size of 200 mesh. After 5 minutes, dry-mix 3.33 g of potassium borohydride and 0.86 g of sodium hydroxide with a particle size of 200 mesh and add them to the isopropanol. Initiate a reflux reaction and react for 1.0 hour. In the second stage, lower the reaction temperature to 70°C, slowly add the remaining 1.05 g of sodium hydroxide in the form of solid powder at a rate of 0.5 g / min, mix evenly, and heat to 80°C at a rate of 0.5°C / min to continue the reaction.

[0052] The mass ratio of potassium borohydride to hydroxide is 1:0.8; the molar ratio of potassium hydroxide to sodium hydroxide is 1:3.

[0053] S200, reflux the mixture at 85° C. for 3 hours.

[0054] S300: Perform atmospheric distillation, controlling the top temperature at 82.3°C, discard the front fraction, and collect the middle fraction; the discarded front fraction should be 5% of the raw material volume; the collected middle fraction should be 85% of the raw material volume; the kettle residue should account for 10%, and the kettle temperature should be controlled at 95°C. S400: Perform UV absorbance and potassium permanganate oxidation tests on the middle fraction to obtain pharmaceutical-grade isopropyl alcohol.

[0055] Example 3

[0056] A preparation process for pharmaceutical-grade isopropyl alcohol comprises the following steps:

[0057] S100. Using 1000 ml of analytical grade isopropanol as the raw material, in the first stage, at a temperature of 80°C, add 0.91 g of potassium hydroxide powder with a particle size of 150 mesh. After 10 minutes, dry-mix 3.81 g of potassium borohydride and 1.8 g of sodium hydroxide with a particle size of 100 mesh and add them to the isopropanol. Initiate a reflux reaction and react for 1.2 hours. In the second stage, lower the reaction temperature to 75°C, slowly add the remaining 1.48 g of sodium hydroxide in the form of solid powder at a controlled addition rate of 0.3 g / min, mix well, and heat to 83°C at a rate of 1.0°C / min to continue the reaction.

[0058] The mass ratio of potassium borohydride to hydroxide is 1:1.1; the molar ratio of potassium hydroxide to sodium hydroxide is 1:5.

[0059] S200, reflux the mixture at 83° C. for 5 hours.

[0060] S300: Perform atmospheric distillation, controlling the top temperature at 82.7°C. Discard the front fraction and collect the middle fraction. The discarded front fraction should be 8% of the raw material volume; the collected middle fraction should be 90% of the raw material volume. The kettle residue should account for 2%, and the kettle temperature should be controlled at 105°C. S400: Perform UV absorbance and potassium permanganate oxidation tests on the middle fraction. If the test meets the standards, pharmaceutical-grade isopropyl alcohol will be obtained.

[0061] Comparative Example 1

[0062] The molar ratio of KOH to NaOH in the hydroxide was 1:1, and other parameters were the same as those in Example 1.

[0063] Comparative Example 2

[0064] The molar ratio of KOH to NaOH in the hydroxide was 1:7, and other parameters were the same as those in Example 1.

[0065] Comparative Example 3

[0066] The hydroxide only includes sodium hydroxide and no potassium hydroxide; other parameters are the same as those in Example 1.

[0067] Comparative Example 4

[0068] Potassium hydroxide, sodium hydroxide and potassium borohydride were mixed by dry method and added into analytical grade isopropanol at one time. Other parameters were the same as those in Example 1.

[0069] The specific methods for detecting the above embodiments and comparative examples are as follows:

[0070] UV absorbance detection method:

[0071] Detection equipment and reagents: UV-2600 UV-visible spectrophotometer, 1 cm quartz cuvette; reference solution is air;

[0072] Sample preparation: The intermediate fraction isopropanol was directly detected without dilution.

[0073] Operation steps: Instrument preheating and calibration: Turn on the instrument and preheat for 30 minutes, set the wavelength range to 230~310 nm; wash the cuvette with high-purity water, and calibrate to zero using air as a blank.

[0074] Sample determination: Take the isopropanol sample to be tested and inject it into a quartz cuvette with the liquid level ≥80%; scan the absorbance (A) at 230 nm, 250 nm, 270 nm, 290 nm, and 310 nm in sequence, and record the maximum value.

[0075] Potassium permanganate oxidation test method: Add 0.5 ml of 0.02 mol / L potassium permanganate solution dropwise to 10 ml of purified isopropyl alcohol sample and let it sit for 15 minutes. If the red color persists, the sample is considered qualified. This method is used to determine the content of easily oxidizable substances in purified isopropyl alcohol.

[0076] The measured impurity content of analytically pure isopropyl alcohol that meets the HG / T2892-2020 standard is shown in Table 1.

[0077] Table 1 Measured impurity content of analytically pure isopropanol

[0078]

[0079] As shown in Table 1, compared with pharmaceutical grade isopropyl alcohol, the analytical grade isopropyl alcohol has the following items exceeding the standard: the content of easily oxidizable substances and benzene compounds exceeds the standard, the ultraviolet absorbance value at 230nm is too high, and the measured values ​​of other items are also close to the standard critical values.

[0080] The impurity contents in the isopropanol after purification using the preparation processes of Examples 1-3 and Comparative Example 4 are shown in Table 2.

[0081] Table 2 Impurity content in isopropyl alcohol after purification using the preparation processes of Examples 1-3 and Comparative Example 4

[0082]

[0083] As shown in Table 2, the easily oxidizable substances in Examples 1-3 of the present invention are detected by potassium permanganate and meet the standards; the carbonyl compound content is reduced to 0.001%~0.004%, and the content is significantly reduced; the benzene compound content is reduced to 0.2ppm from the original 0.0027%, the absorbance at 230nm wavelength is reduced to 0.08~0.102 from the original 0.489, and the absorbance at 250~310nm wavelength is significantly reduced; the content of other impurities is significantly reduced. In Comparative Example 4, after the compounds in the reduction system are mixed uniformly, a one-time input into analytical pure isopropanol is performed, and the carbonyl compound content is significantly higher than that in Examples 1-3, and the absorbance at 230nm wavelength is 0.35, which exceeds the standard value. The potassium permanganate detection shows that the red color disappears completely, which is unqualified. In summary, the preparation process of the present invention can effectively improve the purity of analytical grade isopropyl alcohol by synergistically adding alkali in stages, KBH4 / NaOH reduction and top temperature precision distillation, and improve the purity of analytical grade isopropyl alcohol to the purity of pharmaceutical grade isopropyl alcohol.

[0084] The effects of changing the molar ratio of KOH to NaOH on the reaction and product properties in Examples 1-3 and Comparative Examples 1-3 are shown in Table 3.

[0085] Table 3 Effect of changing the molar ratio of KOH and NaOH on the reaction and product properties

[0086]

[0087] As shown in Table 3, in Examples 1-3, the molar ratio of KOH to NaOH was maintained at 1:3-5, the carbonyl compound content in the purified isopropanol was within the standard range, the utilization rate of KBH4 could reach 95%-99%, and the moisture content was far below the standard value. In Comparative Example 1, the molar ratio of KOH to NaOH was 1:1, and excess NaOH may cause dehydration of isopropanol, resulting in a carbonyl compound content 25 times higher than that of Comparative Examples 1-3. In Comparative Example 2, the molar ratio of KOH to NaOH was 1:7, KOH was insufficient, BH4⁻ was not fully ionized, the carbonyl compound content was 10 times higher than that of Comparative Examples 1-3, and the KBH4 utilization rate was only 88%. In Comparative Example 3, only sodium hydroxide was used without potassium hydroxide, the carbonyl compound content was close to the critical value, the KBH4 utilization rate was only 82%, and the water content was close to the standard value. The molar ratio of potassium hydroxide to sodium hydroxide of the present invention is 1:1-5, which is the optimal range and can effectively balance reduction efficiency and side reaction suppression.

Claims

1. A process for preparing pharmaceutical grade isopropyl alcohol, characterized in that: The following steps are involved: S100, using analytical grade isopropyl alcohol as the raw material, adding potassium borohydride and hydroxide at a solid-liquid ratio of 6-8:1000, and mixing evenly; S200, reflux the mixture at 83-85° C. for 3-5 hours; S300, atmospheric distillation, control the top temperature at 82.3~82.7℃, discard the front fraction, and collect the middle fraction; S400, testing the intermediate fraction, and obtaining pharmaceutical-grade isopropyl alcohol if it meets the standards; Wherein, in step S100, the mass ratio of potassium borohydride to hydroxide is 1:0.8-1.1; the hydroxide is potassium hydroxide and sodium hydroxide, and the molar ratio of potassium hydroxide to sodium hydroxide is 1:3-5; In step S100, the hydroxide is added in stages, including: the first stage: adding potassium borohydride and sodium hydroxide to isopropanol, initiating a reflux reaction, and reacting for 1.0 to 1.2 hours; the second stage: slowly adding the remaining sodium hydroxide in the form of solid powder at an addition rate of ≤0.5 g / min; The particle size of the potassium hydroxide is ≤200 mesh, and the addition time is 5 to 10 minutes before the addition of potassium borohydride; In the first stage, the temperature is 80-85° C., sodium hydroxide and potassium borohydride are dry-mixed and then added to isopropyl alcohol, and the particle size of the sodium hydroxide is 100-200 mesh.

2. The preparation process of pharmaceutical grade isopropyl alcohol according to claim 1, wherein When sodium hydroxide is added in the second stage, the reaction temperature is reduced to 70-75°C. After the addition is completed, the temperature is raised to 80-83°C at a rate of 0.5-1.0°C / min to continue the reaction.

3. The preparation process of pharmaceutical grade isopropyl alcohol according to claim 1, wherein In step S200, the reflux reaction temperature is 81-83°C, the reaction time is 3.8-4.2 hours, and the pH of the reaction system is ≥12.

4. The preparation process of pharmaceutical grade isopropyl alcohol according to claim 1, wherein In step S300, the amount of the discarded front fraction is 5% to 8% of the raw material volume; the volume of the collected middle fraction is 85% to 90% of the raw material volume; the kettle residue accounts for ≤10%, and the kettle temperature is 95 to 105°C.

5. The preparation process of pharmaceutical grade isopropyl alcohol according to claim 1, wherein The detection is selected from ultraviolet absorbance detection and potassium permanganate oxidation detection.

6. The process for preparing pharmaceutical grade isopropyl alcohol according to claim 5, wherein: The wavelength range of ultraviolet light is 230~310nm.

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