Preparation method of R-3-hydroxybutyric acid

Abstract

The invention belongs to the technical field of compounds, and particularly relates to a preparation method of R-3-hydroxybutyric acid. The preparation method of the R-3-hydroxybutyric acid comprises the following steps: hydrolyzing poly-3-hydroxybutyrate, removing impurities, concentrating and dehydrating, extracting, carrying out suction filtration, adjusting acid, decolorizing, carrying out molecular distillation, and drying to obtain the R-3-hydroxybutyric acid. The R-3-hydroxybutyric acid obtained by the preparation method disclosed by the invention has the advantages of high purity, high content, short production period, low equipment requirement, low raw material cost and the like, is suitable for industrial production and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of compounds, and particularly relates to a preparation method of R-3-hydroxybutyric acid. Background Art

[0002] R-3-hydroxybutyric acid (R-3-HB), also known as β-hydroxybutyric acid, has a molecular formula of C4H8O3, a structural formula of CH3CHOHCH2COOH, and a molar mass of 104.10 g / mol. It is the monomer form of the natural polymer poly-R-3-hydroxybutyrate (PHB) and exists in the pure R configuration in its natural state. It is mainly present in the liver, muscles, and brain of the human body and is the most important ketone body in the human body. It has been reported that R-3-hydroxybutyric acid plays an important role in medicine, basic research, and industrial applications and is a multifunctional compound. Its functions include sedation, alleviating anxiety and tension; improving memory, preventing brain atrophy, and preventing and alleviating Alzheimer's disease; preventing osteoporosis; inhibiting cell aging; inhibiting inflammation; improving the problem of insufficient glucose supply to the brain in patients and alleviating symptoms of schizophrenia (SCZ); improving migraine caused by hypoglycemia, free radical peroxidation, and neuronal overexcitation through energy supplementation, antioxidant, and anti-inflammatory effects; improving memory, etc.

[0003] Currently, the preparation of R-3-hydroxybutyric acid has the following problems:

[0004] (1) Yang Wenling et al. studied and published that using acetaldehyde as a raw material, 3-hydroxybutyraldehyde was prepared by aldol condensation, and then the liquid-phase oxidation of 3-hydroxybutyraldehyde was carried out using cobalt acetate catalyst to synthesize 3-hydroxybutyric acid. In this method, high temperature, high pressure, expensive catalysts, and a large amount of organic reagents are used. In addition to the long reaction time required, there are also by-products, which greatly increase the cost.

[0005] (2) Chinese Patent CN112176003A provides a preparation method of R-3-hydroxybutyric acid. In this method, poly-R-3-hydroxybutyrate is pulverized, a buffer solution is added, and then serine esterase and metal salts are added, followed by enzymatic hydrolysis, enzyme inactivation, desalting, etc. to obtain R-3-hydroxybutyric acid. Although the R-3-hydroxybutyric acid prepared by this method has high purity and no heavy metal residues, the process cannot achieve large-scale industrial production.

[0006] (3) Chinese Patent CN201880004349.9 provides a preparation method of R-3-hydroxybutyric acid. This method is a method for directly fermenting non-pathogenic microorganisms to prepare R-3-hydroxybutyric acid or its salt. The method obtains a 3-hydroxybutyric acid fermentation broth through fermentation. During the extraction process, there are large losses, and it is impossible to obtain 3-hydroxybutyric acid with high purity and high content. In addition, the fermentation process is slow, the production cycle is long, the efficiency is low, and the cost is high, etc.

[0007] (4) Patent CN 115448829 A provides a method for preparing R-3-hydroxybutyric acid. First, poly(R)-3-hydroxybutyrate is refluxed and rinsed with an organic solvent, and then the treated poly(R)-3-hydroxybutyrate is hydrolyzed under the catalysis of an acid to obtain (R)-3-hydroxybutyric acid, whose optical purity is not less than 93.18%, mass percentage is not less than 40.13%, and yield is not less than 60.57%. Although the purity of R-3-hydroxybutyric acid prepared by this method is relatively high, the mass percentage is low, and there are problems such as incomplete reaction, high impurity content, and insufficient separation and purification.

[0008] In summary, although there are many methods for preparing R-3-hydroxybutyric acid, they all have deficiencies. Therefore, it is particularly important to develop a method for preparing R-3-hydroxybutyric acid with high purity, high content, simple operation, short production cycle, and low cost. Summary of the Invention

[0009] In view of the problems in the prior art, the present invention provides a method for preparing R-3-hydroxybutyric acid.

[0010] A method for preparing R-3-hydroxybutyric acid includes the following steps:

[0011] Step 1: After poly-3-hydroxybutyrate is hydrolyzed, an impurity-removing solvent is added, and the water phase after impurity removal is concentrated to dryness to obtain a mixture; the impurity-removing solvent is selected from alkane solvents;

[0012] Step 2: The mixture is subjected to extraction, suction filtration, acid adjustment, decolorization, molecular distillation, and drying to obtain R-3-hydroxybutyric acid.

[0013] Preferably, in Step 1, the poly-3-hydroxybutyrate is hydrolyzed in the presence of a basic substance; the basic substance is selected from at least one of potassium hydroxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, calcium hydroxide, barium hydroxide, sodium oxide, calcium oxide, potassium oxide, and sodium ethoxide; the molar ratio of the poly-3-hydroxybutyrate to the basic substance is 1-5:1.

[0014] Preferably, the basic substance is selected from at least one of potassium hydroxide and sodium hydroxide.

[0015] Preferably, in Step 1, the hydrolysis temperature is 60°C - 100°C, and the hydrolysis time is 3 - 6 hours.

[0016] Preferably, in Step 1, the impurity-removing solvent is selected from n-hexane.

[0017] Preferably, in Step 2, the extraction solvent used for extraction is selected from at least one of ethyl acetate, butyl acetate, ethanol, methanol, acetone, butanone, formic acid, acetic acid, and propionic acid; preferably ethanol.

[0018] Preferably, in step 2, the acid adjustment is carried out using a pH regulator, and the pH regulator is selected from at least one of sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid, formic acid, acetic acid, and carbonic acid; the mass fraction of the pH regulator is 10-60%.

[0019] Preferably, the pH regulator is selected from sulfuric acid; the mass fraction of the pH regulator is 20-30%.

[0020] Preferably, in step 2, the reagent used for decolorization is activated carbon; the decolorization time is 20-60 min.

[0021] Preferably, in step 2, the reaction conditions for molecular distillation are: the reaction temperature for separating the heavy-phase fraction is 45-55 °C, and the reaction temperature for separating the light-phase fraction is 70-80 °C.

[0022] The present invention has screened out the optimal preparation method of R-3-hydroxybutyric acid through experiments. By using the method of the present invention, the content and purity of R-3-hydroxybutyric acid can both reach over 95%, and the content of crotonic acid impurities is low. It has the advantages of high content, high purity, short production cycle, low equipment requirements, low raw material cost, and simple production operation, etc., is suitable for industrial production, and has good application prospects.

[0023] Obviously, based on the above content of the present invention, according to the common general knowledge and conventional means in the art, without departing from the above basic technical idea of the present invention, various other forms of modification, substitution or change can also be made.

[0024] The following is a further detailed description of the above content of the present invention through specific embodiments in the form of examples. However, this should not be understood as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention. Description of the Drawings

[0025] Figure 1 It is the liquid chromatography diagram of the mixed standard of R-3-hydroxybutyric acid standard and crotonic acid standard.

[0026] Figure 2 It is the liquid chromatography diagram of crotonic acid standard.

[0027] Figure 3 It is the liquid chromatography diagram of R-3-hydroxybutyric acid extracted by the present invention. Detailed Description of the Embodiments

[0028] In the following examples and experimental examples, the reagents and raw materials not specifically described are all commercially available products.

[0029] Example 1 Preparation Method of R-3-Hydroxybutyric Acid

[0030] Take 100 g of poly-3-hydroxybutyrate (PHB, Yili Weining Biotechnology Co., Ltd., 9385), add it to 2500 mL of 1N sodium hydroxide solution, and hydrolyze at 80 °C for 4 hours. After the hydrolysis is completed, add 1000 mL of n-hexane to the hydrolysis solution for impurity removal. The aqueous phase after impurity removal is concentrated to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top washing, collect the ethanol, add 20% sulfuric acid to adjust the pH to 3, add activated carbon to the acid-adjusted solution (the dosage of activated carbon is 1% of the volume of the acid-adjusted solution, W / V) for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 88%. The decolorized solution is directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flows out, collect the heavy-phase liquid and then perform molecular distillation at 75 °C. When the light-phase fraction no longer flows out, collect the light-phase liquid to obtain high-quality R-3-hydroxybutyric acid with a content of 97%, a purity of 98%, and a crotonic acid content of 0.4% (the content and purity of the product are detected using an Agilent 1260 high-performance liquid chromatograph).

[0031] Preparation method of R-3-hydroxybutyric acid in Example 2

[0032] Take 100 g of PHB, add it to 2500 mL of 2N sodium hydroxide solution, and hydrolyze at 80 °C for 4 hours. After the hydrolysis is completed, add 1000 mL of n-hexane to the hydrolysis solution for impurity removal. The aqueous phase after impurity removal is concentrated to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top washing, collect the ethanol, add 20% sulfuric acid to adjust the pH to 3, add activated carbon to the acid-adjusted solution (the dosage of activated carbon is 1% of the volume of the acid-adjusted solution, W / V) for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 85%. The decolorized solution is directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flows out, collect the heavy-phase liquid and then perform molecular distillation at 75 °C. When the light-phase fraction no longer flows out, collect the light-phase liquid to obtain high-quality R-3-hydroxybutyric acid with a content of 97%, a purity of 96%, and a crotonic acid content of 0.3%.

[0033] Preparation method of R-3-hydroxybutyric acid in Example 3

[0034] Take 100 g of PHB, add it to 2500 mL of 3N sodium hydroxide solution, and hydrolyze at 80 °C for 4 hours. After the hydrolysis is completed, add 1000 mL of n-hexane to the hydrolysis solution for impurity removal. The aqueous phase after impurity removal is concentrated to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top washing, collect the ethanol, add 20% sulfuric acid to adjust the pH to 3, add activated carbon to the acid-adjusted solution (the dosage of activated carbon is 1% of the volume of the acid-adjusted solution, W / V) for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 89%. The decolorized solution is directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flows out, collect the heavy-phase liquid and then perform molecular distillation at 75 °C. When the light-phase fraction no longer flows out, collect the light-phase liquid to obtain high-quality R-3-hydroxybutyric acid with a content of 95%, a purity of 98%, and a crotonic acid content of 0.4%.

[0035] Preparation Method of Example 4 R-3-Hydroxybutyric Acid

[0036] Take 100 g of PHB and add it to 2500 mL of 4N sodium hydroxide solution. Hydrolyze at 80 °C for 4 hours. After hydrolysis, add 1000 mL of n-hexane to the hydrolysis solution for impurity removal. The impurity-removed aqueous phase is concentrated to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top washing, collect the ethanol, add 30% sulfuric acid to adjust the pH to 3, add activated carbon (the dosage of activated carbon is 1% of the volume of the acid-adjusted solution, W / V) to the acid-adjusted solution for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 89%. The decolorized solution is directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flows out, collect the heavy-phase liquid and then perform molecular distillation at 75 °C. When the light-phase fraction no longer flows out, collect the light-phase liquid to obtain high-quality R-3-hydroxybutyric acid with a content of 95%, a purity of 97%, and a crotonic acid content of 0.6%.

[0037] Preparation Method of Example 5 R-3-Hydroxybutyric Acid

[0038] Take 100 g of PHB and add it to 2500 mL of 1N potassium hydroxide solution. Hydrolyze at 80 °C for 4 hours. After hydrolysis, add 1000 mL of n-hexane to the hydrolysis solution for impurity removal. The impurity-removed aqueous phase is concentrated to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top washing, collect the ethanol, add 30% sulfuric acid to adjust the pH to 3, add activated carbon (the dosage of activated carbon is 1% of the volume of the acid-adjusted solution, W / V) to the acid-adjusted solution for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 82%. The decolorized solution is directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flows out, collect the heavy-phase liquid and then perform molecular distillation at 75 °C. When the light-phase fraction no longer flows out, collect the light-phase liquid to obtain high-quality R-3-hydroxybutyric acid with a content of 97%, a purity of 98%, and a crotonic acid content of 0.5%.

[0039] The following is the preparation method of the control sample.

[0040] Preparation Method of Control Example 1 R-3-Hydroxybutyric Acid

[0041] Take 100 g of PHB and add it to 2500 mL of 4N sodium hydroxide solution. Hydrolyze at 80 °C for 4 hours. After hydrolysis, add 1000 mL of n - hexane to the hydrolyzate for impurity removal. Concentrate the aqueous phase after impurity removal to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top - washing, collect the ethanol, add 20% sulfuric acid to adjust the pH to 3. Add activated carbon (the dosage of activated carbon is 1% of the volume of the acid - adjusted solution, W / V) to the acid - adjusted solution for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 86%. First, distill the decolorized solution under reduced pressure at a low temperature of 50 °C. When no more liquid flows out, end the low - temperature reduced - pressure distillation. Collect the non - flowing liquid, which is the crude product of R - 3 - hydroxybutyric acid. Then, perform high - temperature reduced - pressure distillation (140 - 150 °C). When no more distillate fraction flows out, collect the flowing liquid to obtain the refined product of R - 3 - hydroxybutyric acid, with a content of 81%, a purity of 92%, and a crotonic acid content of 5.4%.

[0042] Preparation method of R - 3 - hydroxybutyric acid in Comparative Example 2

[0043] Take 100 g of PHB and add it to 2500 mL of 1N sodium hydroxide solution. Hydrolyze at 80 °C for 4 hours. After hydrolysis, add 1000 mL of n - heptane to the hydrolyzate for impurity removal. Concentrate the aqueous phase after impurity removal to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top - washing, collect the ethanol, add 20% sulfuric acid to adjust the pH to 3. Add activated carbon (the dosage of activated carbon is 1% of the volume of the acid - adjusted solution, W / V) to the acid - adjusted solution for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 83%. Directly subject the decolorized solution to molecular distillation at 50 °C. When the heavy - phase fraction no longer flows out, collect the heavy - phase liquid and then subject it to molecular distillation at 75 °C. When the light - phase fraction no longer flows out, collect the light - phase liquid to obtain the refined product of R - 3 - hydroxybutyric acid, with a content of 95%, a purity of 98%, and a crotonic acid content of 4.7%.

[0044] Preparation method of R - 3 - hydroxybutyric acid in Comparative Example 3

[0045] Take 100 g of PHB and add it to 2500 mL of 1N sodium hydroxide solution. Hydrolyze at 80 °C for 4 hours. After hydrolysis, add 1000 mL of petroleum ether to the hydrolyzate for impurity removal. Concentrate the aqueous phase after impurity removal to dryness at 80 °C, add 1000 mL of ethanol for extraction for 30 min, filter by suction, wash the filter cake with ethanol for top - washing, collect the ethanol solution, add 20% sulfuric acid to adjust the pH to 3. Add activated carbon (the dosage of activated carbon is 1% of the volume of the acid - adjusted solution, W / V) to the acid - adjusted solution for decolorization for 30 min, filter by suction to obtain the decolorized solution, and the hydrolysis yield is 80%. Directly subject the decolorized solution to molecular distillation at 50 °C. When the heavy - phase fraction no longer flows out, collect the heavy - phase liquid and then subject it to molecular distillation at 75 °C. When the light - phase fraction no longer flows out, collect the light - phase liquid to obtain the refined product of R - 3 - hydroxybutyric acid, with a content of 80%, a purity of 86%, and a crotonic acid content of 20.5%.

[0046] Preparation method of R - 3 - hydroxybutyric acid in Comparative Example 4

[0047] 100 g of PHB was added to 2500 mL of 1N potassium hydroxide solution and hydrolyzed at 80 °C for 4 hours. After the hydrolysis was completed, 1000 mL of ethyl acetate was added to the hydrolyzate for impurity removal. The aqueous phase after impurity removal was concentrated to dryness at 80 °C, 1000 mL of ethanol was added for extraction for 30 min, followed by suction filtration. The filter cake was rinsed with ethanol, and the ethanol solution was collected. 20% sulfuric acid was added to adjust the pH to 3. Activated carbon (the dosage of activated carbon was 1% of the volume of the acid-adjusted solution, W / V) was added to the acid-adjusted solution for decolorization for 30 min, followed by suction filtration to obtain the decolorized solution. The hydrolysis yield was 76%. The decolorized solution was directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flowed out, the heavy-phase liquid was collected and then subjected to molecular distillation at 75 °C. When the light-phase fraction no longer flowed out, the light-phase liquid was collected to obtain high-quality R-3-hydroxybutyric acid with a content of 85%, a purity of 83%, and a crotonic acid content of 13.2%.

[0048] Preparation method of R-3-hydroxybutyric acid in Comparative Example 5

[0049] 100 g of PHB was added to 2500 mL of 1N sodium hydroxide solution and hydrolyzed at 80 °C for 4 hours. After the hydrolysis was completed, 1000 mL of n-hexane was added to the hydrolyzate for impurity removal. The aqueous phase after impurity removal was concentrated to dryness at 80 °C, 1000 mL of ethyl acetate was added for extraction for 30 min, followed by suction filtration. The filter cake was rinsed with ethanol, and the ethanol solution was collected. 30% sulfuric acid was added to adjust the pH to 3. Activated carbon (the dosage of activated carbon was 1% of the volume of the acid-adjusted solution, W / V) was added to the acid-adjusted solution for decolorization for 30 min, followed by suction filtration to obtain the decolorized solution. The hydrolysis yield was 66%. The decolorized solution was directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flowed out, the heavy-phase liquid was collected and then subjected to molecular distillation at 75 °C. When the light-phase fraction no longer flowed out, the light-phase liquid was collected to obtain high-quality R-3-hydroxybutyric acid with a content of 95%, a purity of 98%, and a crotonic acid content of 6.1%.

[0050] Preparation method of R-3-hydroxybutyric acid in Comparative Example 6

[0051] 100 g of PHB was added to 2500 mL of 1N sodium hydroxide solution and hydrolyzed at 80 °C for 4 hours. After the hydrolysis was completed, 1000 mL of n-hexane was added to the hydrolyzate for impurity removal. The aqueous phase after impurity removal was concentrated to dryness at 80 °C, 1000 mL of methanol was added for extraction for 30 min, followed by suction filtration. The filter cake was rinsed with methanol, and the methanol was collected. 30% sulfuric acid was added to adjust the pH to 3. Activated carbon (the dosage of activated carbon was 1% of the volume of the acid-adjusted solution, W / V) was added to the acid-adjusted solution for decolorization for 30 min, followed by suction filtration to obtain the decolorized solution. The hydrolysis yield was 80%. The decolorized solution was directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flowed out, the heavy-phase liquid was collected and then subjected to molecular distillation at 75 °C. When the light-phase fraction no longer flowed out, the light-phase liquid was collected to obtain high-quality R-3-hydroxybutyric acid with a content of 97%, a purity of 98%, and a crotonic acid content of 1.2%.

[0052] Preparation method of R-3-hydroxybutyric acid in Comparative Example 7

[0053] 100 g of PHB was added to 2500 mL of 1 N sodium hydroxide solution and hydrolyzed at 80 °C for 4 hours. After hydrolysis, 1000 mL of n-hexane was added to the hydrolysis solution for impurity removal. The aqueous phase after impurity removal was concentrated to dryness at 80 °C, 1000 mL of acetone was added for extraction for 30 min, followed by suction filtration. The filter cake was rinsed with acetone, and the acetone was collected. 30% sulfuric acid was added to adjust the pH to 3. Activated carbon (the dosage of activated carbon was 1% of the volume of the acid-adjusted solution, W / V) was added to the acid-adjusted solution for decolorization for 30 min, followed by suction filtration to obtain the decolorized solution. The hydrolysis yield was 54%. The decolorized solution was directly subjected to molecular distillation at 50 °C. When the heavy-phase fraction no longer flowed out, the heavy-phase liquid was collected and further subjected to molecular distillation at 75 °C. When the light-phase fraction no longer flowed out, the light-phase liquid was collected to obtain high-quality R-3-hydroxybutyric acid with a content of 89%, a purity of 95%, and a crotonic acid content of 13.2%.

[0054] The differences between the preparation methods of R-3-hydroxybutyric acid in the examples and the control examples are summarized as follows (Table 1).

[0055] Table 1

[0056]

[0057] As can be seen from Table 1, when preparing R-3-hydroxybutyric acid by the method of the present invention, alkaline reagents such as sodium hydroxide and potassium hydroxide with a concentration of 1-4 N are used during hydrolysis. According to the hydrolysis yield, the hydrolysis yield does not differ much at a concentration of 1-4 N. Therefore, choosing low-concentration hydrolysis is more likely to obtain high-purity products and can reduce costs at the same time; the pH regulator is 20%-30% sulfuric acid; n-hexane is selected as the impurity removal solvent, ethanol is selected as the extraction solvent, and when molecular distillation is selected as the distillation method, the prepared R-3-hydroxybutyric acid has a high content (>95%), a high purity (>95%), and a low content of crotonic acid impurities.

[0058] The content of R-3-hydroxybutyric acid refers to the mass fraction of R-3-hydroxybutyric acid in the mixed solution (decolorized solution); the purity of R-3-hydroxybutyric acid refers to the mass percentage of R-3-hydroxybutyric acid in the substances detected by a high-performance liquid chromatograph for the finally obtained high-quality R-3-hydroxybutyric acid, that is, the chromatographic purity; the crotonic acid content refers to the mass fraction of crotonic acid in the mixed solution (decolorized solution).

[0059] The beneficial effects of the present invention are further illustrated by the following experimental examples.

[0060] Experimental Example 1: Identification of R-3-hydroxybutyric acid

[0061] I. Experimental method

[0062] The product prepared in Example 1 was subjected to liquid chromatography testing.

[0063] II. Experimental results

[0064] The results are as Figures 1-3 shown Figure 1 the liquid chromatography diagram of the mixed standard of R-3-hydroxybutyric acid standard and crotonic acid standard Figure 2 the liquid chromatography diagram of crotonic acid standard Figure 3 the liquid chromatography diagram of R-3-hydroxybutyric acid prepared by using the present invention. In the chromatography diagram, the response time of the R-3-hydroxybutyric acid product is consistent with that of the R-3-hydroxybutyric acid standard; the response time of crotonic acid in the R-3-hydroxybutyric acid product is consistent with that of the crotonic acid standard. The results show that the present invention successfully prepares R-3-hydroxybutyric acid.

[0065] In summary, the present invention screens out the best preparation method of R-3-hydroxybutyric acid through experiments. By using the method of the present invention, the content and purity of R-3-hydroxybutyric acid can both reach more than 95%, and the content of crotonic acid impurities is low. It has the advantages of high content, high purity, short production cycle, low equipment requirements, low raw material cost, simple production operation, etc., is suitable for industrial production, and has good application prospects.

Claims

1. A method for preparing R-3-hydroxybutyric acid, characterized in that: The steps include: Step 1: After the poly-3-hydroxybutyrate is hydrolyzed, a decontamination solvent is added, and the decontamination aqueous phase is concentrated to dryness to obtain a mixture; the decontamination solvent is selected from an alkane solvent; Step 2: The mixture is subjected to extraction, suction filtration, acid adjustment, decolorization, molecular distillation, and drying to obtain R-3-hydroxybutyric acid.

2. The preparation method according to claim 1, characterized in that: In step 1, the poly-3-hydroxybutyrate is hydrolyzed under alkaline substances; the alkaline substances are selected from at least one of potassium hydroxide, sodium hydroxide, sodium carbonate, sodium bicarbonate, calcium hydroxide, barium hydroxide, sodium oxide, calcium oxide, potassium oxide, and sodium ethoxide; the molar ratio of the poly-3-hydroxybutyrate to the alkaline substance is 1 to 5:

1.

3. The preparation method according to claim 2, characterized in that: The alkaline substance is selected from at least one of potassium hydroxide and sodium hydroxide.

4. The preparation method according to claim 1, characterized in that: In step 1, the hydrolysis temperature is 60° C. to 100° C., and the hydrolysis time is 3 to 6 hours.

5. The preparation method according to claim 1, characterized in that: In step 1, the impurity-removing solvent is selected from n-hexane.

6. The preparation method according to claim 1, characterized in that: In step 2, the extraction solvent used in the extraction is selected from at least one of ethyl acetate, butyl acetate, ethanol, methanol, acetone, butanone, formic acid, acetic acid, and propionic acid; preferably ethanol.

7. The preparation method according to claim 1, characterized in that: In step 2, the acid is adjusted by a pH adjusting agent, and the pH adjusting agent is selected from at least one of sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid, formic acid, acetic acid, and carbonic acid; the mass fraction of the pH adjusting agent is 10 to 60%.

8. The preparation method according to claim 7, characterized in that: The pH regulator is selected from sulfuric acid; the mass fraction of the pH regulator is 20-30%.

9. The preparation method according to claim 1, characterized in that: In step 2, the decolorization reagent is activated carbon; and the decolorization time is 20 to 60 minutes.

10. The preparation method according to claim 1, characterized in that: In step 2, the reaction conditions of the molecular distillation are: the reaction temperature for separating the heavy phase fraction is 45-55°C, and the reaction temperature for separating the light phase fraction is 70-80°C.

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