A method for extracting 4-vinylphenol from a fermentation broth and inhibiting its polymerization
By using a combination of 2,6-di-tert-butyl-p-cresol and sodium bisulfite with a mixed solvent of ethyl acetate and n-hexane, the extraction process was optimized, solving the problem of easy polymerization of 4-vinylphenol in fermentation broth, achieving efficient extraction and high-purity production, and reducing production costs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HANGZHOU VIABLIFE BIOTECH CO LTD
- Filing Date
- 2026-02-27
- Publication Date
- 2026-06-05
AI Technical Summary
In the process of extracting 4-vinylphenol from fermentation broth, 4-vinylphenol is prone to self-polymerization, which leads to a decrease in the yield of the target product, an increase in the difficulty of separation and purification, and an increase in production costs. Existing methods are difficult to effectively inhibit its polymerization.
A complex system of 2,6-di-tert-butyl-p-cresol and sodium bisulfite was used as a polymerization inhibitor, combined with a mixed solvent of ethyl acetate and n-hexane as an organic extractant. 4-vinylphenol was extracted by extraction, vacuum distillation and recrystallization, and the extraction process was optimized to inhibit its polymerization.
It significantly reduces the polymerization rate of 4-vinylphenol, improves extraction efficiency and product yield, reduces production costs, and achieves high-purity 4-vinylphenol products, showing good prospects for industrial application.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of biochemical product extraction technology, and more specifically, to a method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization. Background Technology
[0002] 4-Ethylphenol, also known as p-vinylphenol, has the chemical formula C8H8O. It possesses a medicinal phenolic odor and a musty aroma; when diluted, it has a sweet and vanilla-like fragrance. It is commonly used as a food flavoring agent, especially in meat and seafood flavor formulations. It is naturally found in foods such as apples and wine. As an important fine chemical intermediate, 4-ethenylphenol is widely used in food flavorings, pharmaceutical synthesis, and polymer materials.
[0003] Currently, the production of 4-vinylphenol via microbial fermentation has become the mainstream direction for industrial production due to its advantages such as wide availability of raw materials and environmental friendliness. However, during the extraction of 4-vinylphenol from the fermentation broth, the unsaturated double bonds in the 4-vinylphenol molecule make it chemically reactive and prone to self-polymerization, generating impurities such as dimers and polymers. This not only leads to a significant reduction in the yield of the target product but also increases the difficulty of subsequent separation and purification, raising production costs and severely restricting the economic benefits of industrial-scale 4-vinylphenol production.
[0004] Common methods for extracting 4-vinylphenol from fermentation broth include organic solvent extraction, distillation, and resin adsorption. Among these, organic solvent extraction is the most widely used due to its simplicity and high extraction efficiency. However, traditional organic solvent extraction processes typically focus only on extraction efficiency and fail to take effective measures to control the polymerization of 4-vinylphenol, leading to severe polymerization during the extraction process. Some studies have attempted to inhibit polymerization by lowering the extraction temperature, but low-temperature operation increases equipment energy consumption and operating costs, and has limited inhibitory effect on polymerization. Other studies have used the addition of antioxidants, but known antioxidants are difficult to adapt to the complex system environment of fermentation broth and cannot achieve efficient and stable inhibition of polymerization.
[0005] Therefore, developing a method that can significantly reduce the polymerization reaction of 4-vinylphenol while ensuring efficient extraction has become an urgent problem to be solved in this field.
[0006] In view of this, the present invention is proposed. Summary of the Invention
[0007] The purpose of this invention is to provide a method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization. The method of this invention can achieve efficient extraction of 4-vinylphenol while effectively inhibiting its polymerization reaction, thereby improving the yield and purity of the target product and reducing production costs.
[0008] This invention is implemented as follows: In a first aspect, the present invention provides a polymerization inhibitory composition comprising 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 2 to 3:1.
[0009] In a second aspect, the present invention provides the use of the above composition in inhibiting the polymerization of 4-vinylphenol in fermentation broth.
[0010] Thirdly, the present invention provides a method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization, comprising: adding an organic extractant and the above-mentioned composition to the fermentation broth, performing extraction treatment, and collecting the upper organic phase; then subjecting the organic phase to vacuum distillation to obtain crude 4-vinylphenol; and then recrystallizing the crude 4-vinylphenol to obtain 4-vinylphenol.
[0011] The present invention has the following beneficial effects: This invention addresses the issue of the easy polymerization reaction of 4-vinylphenol by optimizing existing polymer inhibitors and applying them to the extraction of 4-vinylphenol from fermentation broth. Simultaneously, the extraction agent and extraction process are optimized. The resulting new extraction method not only efficiently extracts 4-vinylphenol but also significantly reduces polymerization reactions, improves the yield and purity of the target product, and lowers production costs. Furthermore, the organic extraction agent used can be recycled, reducing both raw material costs and environmental impact. Therefore, the polymer inhibitor and the method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization provided by this invention have promising prospects for industrial application. Detailed Implementation
[0012] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.
[0013] Through long-term production practice, the inventors discovered that severe polymerization occurs during the extraction of 4-vinylphenol from fermentation broth. The resulting impurities reduce the quality of the target product and increase the difficulty of separation and purification, thereby raising production costs. To address this issue, the inventors discovered a specific composition that can effectively inhibit the polymerization of 4-vinylphenol.
[0014] In this invention, the above composition includes 2,6-di-tert-butyl-p-cresol (BHT) and sodium bisulfite in a mass ratio of 2 to 3:1.
[0015] This invention uses a compound system of 2,6-di-tert-butyl-p-cresol and sodium bisulfite as a polymerization inhibitor. The two work synergistically to effectively capture free radicals generated during the polymerization of 4-vinylphenol, while inhibiting the promoting effect of oxidation on polymerization, thus significantly reducing the polymerization rate of 4-vinylphenol during the extraction process.
[0016] Based on this, the present invention further optimizes the extraction method of 4-vinylphenol, which includes: adding an organic extractant and the above composition to the fermentation broth, performing extraction treatment, and collecting the upper organic phase; then performing vacuum distillation on the organic phase to obtain crude 4-vinylphenol; and then recrystallizing the crude 4-vinylphenol to obtain 4-vinylphenol.
[0017] The fermentation broth used in this invention is a fermentation broth containing 4-vinylphenol prepared using yeast, lactic acid bacteria, or Escherichia coli as engineered strains. The preparation method can refer to conventional methods, and this invention does not specifically limit it. Initially, the concentration of 4-vinylphenol in the fermentation broth is 4-8 g / L, and the pH range of the fermentation broth is 5-8.
[0018] In some embodiments, the initial concentration of 4-vinylphenol in the fermentation broth is 5-8 g / L, and the pH range of the fermentation broth is 6.5-7.0.
[0019] Specifically, the method for extracting 4-vinylphenol from fermentation and inhibiting its polymerization provided by the present invention is as follows: S1. Fermentation broth pretreatment: The 4-vinylphenol fermentation broth containing microorganisms is filtered to obtain a clear filtrate, and then its pH is adjusted to 2.0~3.0.
[0020] The purpose of filtration is to remove solid impurities such as cell bodies and mycelia from the fermentation broth; the purpose of adjusting the pH of the filtrate is to increase the solubility of 4-vinylphenol in organic reagents in subsequent steps.
[0021] S2. Organic reagent extraction and polymerization inhibition: Add organic extractant and the above-mentioned polymerization inhibitor to the pretreated fermentation broth, stir and extract, let stand and separate into layers, collect the upper organic phase, and perform a second extraction on the lower aqueous phase, and combine the two organic phases.
[0022] In some embodiments, the polymerization inhibitor is composed of 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 2 to 3:1.
[0023] In some embodiments, the organic extractant consists of ethyl acetate and n-hexane in a volume ratio of (3-5):1. This invention selects a mixed solvent of ethyl acetate and n-hexane as the organic extractant because the combination of the two, at a specific volume ratio, enables the mixed solvent to exhibit good selectivity and solubility for 4-vinylphenol. Other conventional extractants, due to excessively high or low polarity, cannot achieve good extraction results for 4-vinylphenol.
[0024] In some embodiments, the volume ratio of fermentation broth to organic extractant is 1:0.8 to 1.2; the amount of the above composition added is 0.5% to 2.0% of the mass of 4-vinylphenol in the fermentation broth.
[0025] By employing the polymer inhibitor and organic extractant of this invention, the polymerization rate of 4-vinylphenol in the fermentation broth is greatly reduced, and can be controlled below 3%, which is far lower than the polymerization rate of 15% to 20% of traditional extraction methods; it also significantly improves the extraction efficiency, with a single extraction rate of over 90%, and after two extractions, the total extraction rate can reach over 98%, which is significantly higher than that of traditional single organic solvents.
[0026] In some embodiments, the extraction conditions are: temperature of 25~35℃, stirring speed of 150~200 rpm / min, and time of 20~30 min.
[0027] S3. Organic phase removal and purification: The combined organic phases are transferred to a vacuum distillation apparatus for vacuum distillation to obtain crude 4-vinylphenol. Then, the crude 4-vinylphenol is added to anhydrous ethanol and heated to 50-60°C to completely dissolve the crude product. Then, pure water is slowly added, stirred to induce crystallization, and filtered to obtain 4-vinylphenol.
[0028] In this process, vacuum distillation removes organic extractants, which can then be recycled and reused. This not only reduces the amount of polymerization inhibitors needed and lowers raw material costs, but also reduces environmental pressure.
[0029] This invention optimizes polymerization inhibitors, extraction processes, and subsequent recrystallization purification by adding a pretreatment step to the extraction method. The resulting new extraction method can effectively remove impurities from the fermentation broth, improve the extraction efficiency and quality of 4-vinylphenol, and reduce production costs.
[0030] The features and performance of the present invention will be further described in detail below with reference to embodiments.
[0031] Example 1 This embodiment provides a composition for inhibiting the polymerization of 4-vinylphenol in fermentation broth. The composition consists of 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 2.5:1.
[0032] Example 2 This embodiment provides a composition for inhibiting the polymerization of 4-vinylphenol in fermentation broth. The composition consists of 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 2:1.
[0033] Example 3 This embodiment provides a composition for inhibiting the polymerization of 4-vinylphenol in fermentation broth. The composition consists of 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 3:1.
[0034] Example 4 This embodiment describes a method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization. The operation steps are as follows: (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0035] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 1, the amount of which is 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0036] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0037] According to the test results, the total yield of 4-vinylphenol in this example was 92.3%, the purity of the refined product was 99.7%, and the polymerization rate was 2.1%.
[0038] Example 5 (1) Pretreatment of fermentation broth Take 8 L of lactic acid bacteria fermentation broth containing 4-vinylphenol, centrifuge and filter at 5000 rpm / min for 10 min to remove bacterial impurities and obtain clear fermentation filtrate; 2) Add 98% sulfuric acid dropwise to the fermentation filtrate to adjust the pH to 2.0; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 32 g.
[0039] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate into a 30 L extraction vessel and add 6.4 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 3:1); add the composition of Example 2, the amount added is 0.8% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount added is 0.256 g). 2) At 25℃, the mixture was stirred and extracted for 20 min at a stirring rate of 150 rpm / min. After standing and separating into layers, the upper organic phase was collected; the lower aqueous phase was extracted a second time, and the organic phases were combined.
[0040] (3) Organic phase removal and purification 1) The combined organic phases were distilled under reduced pressure at a vacuum of 0.08 MPa and a distillation temperature of 40℃ to recover the organic extractant and obtain crude 4-vinylphenol. 2) Add anhydrous ethanol to crude 4-vinylphenol (mass ratio of crude product to anhydrous ethanol is 1:4), heat to 50℃ to dissolve, then slowly add pure water at a rate of 10 ml / min, the amount of pure water is 1 / 2 of the ethanol, cool to 4℃, let stand for 2 h for recrystallization, cool to 4℃ for recrystallization, filter to obtain the purified product.
[0041] According to the test results, the total yield of 4-vinylphenol in this example was 90.5%, the purity of the refined product was 99.6%, and the polymerization rate was 2.8%.
[0042] Example 6 The difference from Example 4 is that this composition is the same as the composition in Example 3.
[0043] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The fermentation filtrate contained 50g of 4-vinylphenol.
[0044] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 3, the amount added is 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0045] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0046] According to the test results, the total yield of 4-vinylphenol in this example was 95.4%, the purity of the refined product was 99.74%, and the polymerization rate was 1.5%.
[0047] Example 7 The difference from Example 4 is that the volume ratio of ethyl acetate to n-hexane in the organic extractant is 5:1.
[0048] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0049] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 5:1); at the same time, add the composition of Example 1, the amount of which is 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0050] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0051] According to the test results, the total yield of 4-vinylphenol in this example was 93.7%, the purity of the refined product was 99.72%, and the polymerization rate was 2.01%.
[0052] Example 8 The difference from Example 4 is that the amount of this composition added is 0.5% of the mass of 4-vinylphenol in the fermentation broth.
[0053] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0054] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 1, the amount of which is 0.5% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.25 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0055] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0056] According to the test results, the total yield of 4-vinylphenol in this example was 84.1%, the purity of the refined product was 98.69%, and the polymerization rate was 4.6%.
[0057] Example 9 The difference from Example 4 is that the amount of this composition added is 2.0% of the mass of 4-vinylphenol in the fermentation broth.
[0058] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0059] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 1, the amount of which is 2.0% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 1.0 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0060] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0061] According to the test results, the total yield of 4-vinylphenol in this example was 96.7%, the purity of the refined product was 99.76%, and the polymerization rate was 0.9%.
[0062] Comparative Example 1 The difference from Example 4 is that the polymerization inhibitor used is p-hydroxyanisole (a commonly used polymerization inhibitor for phenolic products).
[0063] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0064] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add p-hydroxyanisole, the amount of which is 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0065] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0066] The test results showed that the total yield of 4-vinylphenol in this experiment was 67.9%, the purity of the refined product was 92.6%, the polymerization rate was 6.3%, and the finished product was yellow in color and severely sticky.
[0067] Comparative Example 2 The difference from Example 4 is that the polymerization inhibitor used is 2,6-di-tert-butyl-p-cresol.
[0068] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0069] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add 2,6-di-tert-butyl-p-cresol at a rate of 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0070] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0071] The test results showed that the total yield of 4-vinylphenol in this experiment was 70.02%, the purity of the refined product was 93.3%, the polymerization rate was 4.1%, the state was not very loose and brittle, and the color was normal.
[0072] Comparative Example 3 The difference from Example 4 is that sodium sulfite was used as the polymerization inhibitor.
[0073] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0074] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 1, the amount of which is 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0075] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0076] The test results showed that the total yield of 4-vinylphenol in this experiment was 52.7%, the purity of the refined product was 89.2%, the polymerization rate was 12.7%, and the finished product was yellow in color and severely sticky.
[0077] Comparative Example 4 The difference from Example 4 is that this composition uses p-hydroxyanisole instead of sodium sulfite.
[0078] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0079] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, mix the two according to the mixing ratio in Example 1 to form a new polymerization inhibitor composition, with the amount added being 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0080] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0081] The test results showed that the total yield of 4-vinylphenol in this experiment was 94.3%, the purity of the refined product was 98.7%, and the polymerization rate was 3.6%. However, the product was darker in color and the content was slightly lower. This should be related to the fact that the antioxidant properties of p-hydroxyanisole are not as good as those of sodium sulfite. In addition, p-hydroxyanisole is not easy to remove from the crystallization process of the product.
[0082] Comparative Example 5 The difference from Example 4 is that this composition uses p-hydroxyanisole instead of 2,6-di-tert-butyl-p-cresol.
[0083] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0084] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, mix the two components according to the proportion in Example 1 to form a new composition, with the amount added being 1.2% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 0.6 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0085] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0086] The test results showed that the total yield of 4-vinylphenol in this experiment was 87.6%, the purity of the refined product was 91.5%, the polymerization rate was 6.5%, the color was slightly yellow, and it was slightly sticky.
[0087] Comparative Example 6 The difference from Example 4 is that the amount of this composition added is 4.0% of the mass of 4-vinylphenol in the fermentation broth.
[0088] (1) Pretreatment of fermentation broth 1) Take 10 L of yeast fermentation broth containing 4-vinylphenol, filter it using a plate and frame filter press to remove cell impurities, and obtain a clear fermentation filtrate; 2) Add 85% phosphoric acid solution to the fermentation filtrate to adjust the pH to 2.5; 3) The mass of 4-vinylphenol in the fermentation filtrate was found to be 50 g.
[0089] (2) Organic reagent extraction and polymerization inhibition 1) Transfer the pretreated fermentation filtrate to a 50 L extraction vessel and add 10 L of organic extractant (ethyl acetate to n-hexane in a volume ratio of 4:1); at the same time, add the composition of Example 1, the amount of which is 4.0% of the mass of 4-vinylphenol in the fermentation filtrate (i.e., the amount of the composition added is 2 g). 2) At 30°C, the mixture was stirred and extracted for 25 min at a stirring rate of 180 rpm / min. After standing and separating into layers, the upper organic phase was collected. The lower aqueous phase was extracted a second time under the same conditions as above, and the two organic phases were combined.
[0090] (3) Organic phase removal and purification 1) The combined organic phases are transferred into a vacuum distillation column and vacuum distilled at a vacuum degree of 0.085 MPa and a distillation temperature of 45℃ to recover the organic extractant (the recovery rate can reach more than 95%). After the organic extractant is removed, crude 4-vinylphenol is obtained. 2) Add the crude product to anhydrous ethanol at a mass ratio of 1:5, heat to 55°C to completely dissolve the crude product, then slowly add pure water at a rate of 10 ml / min, with the amount of pure water being 1 / 2 of the ethanol volume, cool to 0°C, let stand for 2 h for recrystallization, and filter to obtain the refined 4-vinylphenol.
[0091] The test results showed that the total yield of 4-vinylphenol in this experiment was 95.7%, the purity of the refined product was 97.3%, and the polymerization rate was 1.45%. However, the content of the finished product was low, and the residual amount of polymerization inhibitor was high.
[0092] Comparative Example 7 The difference from Example 4 is that the mass ratio of 2,6-di-tert-butyl-p-cresol to sodium bisulfite in this composition is 4:1.
[0093] The test results showed that the total yield of 4-vinylphenol in this experiment was 93.98%, the purity of the refined product was 99.69%, and the polymerization rate was 1.89%. The main problem was the slightly yellow color caused by insufficient sodium bisulfite.
[0094] Comparative Example 8 The difference from Example 4 is that the organic extractant is ethyl acetate.
[0095] The test results showed that the total yield of 4-vinylphenol in this experiment was 93.01%, the purity of the refined product was 98.04%, and the polymerization rate was 2.03%. The main problems were that the polarity was slightly high, resulting in more impurities being extracted and the content being low.
[0096] Comparative Example 9 The difference from Example 4 is that the organic extractant is n-hexane.
[0097] The results showed that the total yield of 4-vinylphenol in this experiment was 65.32%, the purity of the refined product was 99.80%, and the polymerization rate was 2.0%. The main problem was that the polarity was too low, resulting in insufficient extraction and a low yield.
[0098] Comparative Example 10 The difference from Example 4 is that the volume ratio of the organic extractant to the fermentation broth is 2:1.
[0099] Testing revealed that the total yield of 4-vinylphenol in this example was 92.76%, the purity was 99.13%, and the polymerization rate was 2.1%. While there was no significant improvement in the product quality, the processing efficiency decreased due to the increased solvent system, and the amount of impurities removed increased slightly.
[0100] The yield and purity of 4-vinylphenol extracted in Examples 4-9 and Comparative Examples 1-10 were statistically analyzed, and the results are shown in Table 1: Table 1. Extraction efficiency of 4-vinylphenol in each group of experiments
[0101] Based on the above results, it can be seen that, compared with comparative examples 1-10, the present invention, through the selection of specific polymerization inhibitor components, proportions and amounts, as well as extraction reagents, enables the present invention to reduce the polymerization rate of 4-vinylphenol in the fermentation broth and significantly improve the extraction efficiency when extracting 4-vinylphenol from the fermentation broth.
[0102] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A polymerization inhibition composition characterized in that, The composition comprises 2,6-di-tert-butyl-p-cresol and sodium bisulfite in a mass ratio of 2 to 3:
1.
2. The use of the composition of claim 1 in inhibiting the polymerization of 4-vinylphenol in fermentation broth.
3. A method for extracting 4-vinylphenol from fermentation broth and inhibiting its polymerization, characterized in that, include: An organic extractant and the composition of claim 1 were added to the fermentation broth for extraction, and the upper organic phase was collected. The organic phase was then subjected to vacuum distillation to obtain crude 4-vinylphenol; the crude 4-vinylphenol was then recrystallized to obtain 4-vinylphenol.
4. The method according to claim 3, characterized in that, The organic extractant includes ethyl acetate and n-hexane.
5. The method according to claim 4, characterized in that, The volume ratio of ethyl acetate to n-hexane in the organic extractant is (3~5):
1.
6. The method according to claim 5, characterized in that, In the extraction system, the volume ratio of fermentation broth to the organic extractant is 1:0.8~1.2; the amount of the composition added is 0.5%~2.0% of the mass of 4-vinylphenol in the fermentation broth.
7. The method according to claim 3, characterized in that, The extraction conditions are: temperature 25~35℃, stirring speed 150~200 rpm / min, and time 20~30 min.
8. The method according to claim 3, characterized in that, The conditions for vacuum distillation are: vacuum degree of 0.08~0.09 MPa and distillation temperature of 40~50℃.
9. The method according to claim 3, characterized in that, The recrystallization step includes: adding the crude 4-vinylphenol to anhydrous ethanol, heating to 50-60°C to completely dissolve the crude product, then slowly adding pure water, stirring to induce crystallization, and filtering to obtain 4-vinylphenol.
10. The method according to claim 3, characterized in that, The fermentation broth also includes pretreatment before extraction; the pretreatment steps include: filtering the 4-vinylphenol fermentation broth containing microorganisms to obtain a clear filtrate, and then adjusting its pH to 2.0~3.0.