A method for synthesizing 3-hydroxyhexanoate from n-butyraldehyde

Abstract

The application provides a method for synthesizing 3-hydroxyhexanoate by using n-butyraldehyde. The method specifically comprises the following steps: under the action of a Lewis acid catalyst and a sulfide assistant, n-butyraldehyde and ethenone are condensed to obtain a low-molecular polyester; the low-molecular polyester is converted into a beta-n-propyl propiolactone intermediate by performing depolymerization; and the intermediate and alcohol are reacted to obtain 3-hydroxyhexanoate. The raw material n-butyraldehyde and methanol used in the method are cheap and easy to obtain, and the other ethenone can be obtained by high-temperature cracking of acetic acid. The synthesis route is novel, the total yield can be up to 85%, almost no three wastes are generated, and the method has a good cost advantage. The Lewis acid catalyst and the sulfide assistant are used to synergistically catalyze the condensation of n-butyraldehyde and ethenone, and the selectivity is increased from 87% to 96%.

Description

Technical Field

[0001] This invention belongs to the field of fine chemicals, specifically relating to a method for synthesizing 3-hydroxyhexanoate from n-butyraldehyde. Background Technology

[0002] Ethyl 3-hydroxyhexanoate is a colorless or pale yellow liquid at room temperature with a fresh fruity aroma. It is a commonly used fruit flavoring. Ethyl 3-hydroxyhexanoate is naturally found in fruits such as sweet oranges, pineapples, grapefruits, and papayas. It is a food flavoring permitted by national standards and can be used in baked goods, beverages, jellies, jams, and other foods. Because the content of ethyl 3-hydroxyhexanoate in fruits is very low, natural extraction is expensive and costly. Therefore, the currently economical and low-cost method to obtain ethyl 3-hydroxyhexanoate is artificial synthesis. Methyl 3-hydroxyhexanoate has similar physical and chemical properties to ethyl 3-hydroxyhexanoate. It is also a colorless or pale yellow liquid at room temperature, insoluble in water, and naturally found in fruits such as strawberries, pineapples, apples, and Valencia oranges. It is a natural equivalent flavoring and is also widely used in baked goods, beverages, jellies, jams, and other foods.

[0003] Patent CN110803989 reports a method for synthesizing ethyl 3-hydroxyhexanoate from n-butyraldehyde, acetic acid, and bromine as raw materials; bromine and acetic acid are used to synthesize ethyl bromoacetate, and n-butyraldehyde and ethyl bromoacetate are condensed to obtain ethyl 3-hydroxyhexanoate; this method has a long synthetic route and many reaction steps, and the production process requires the consumption of expensive bromine and generates a large amount of waste bromine salt, which is difficult to handle.

[0004]

[0005] Some literature reports the direct esterification of 3-hydroxyhexanoic acid and methanol under acidic catalysis to obtain methyl 3-hydroxyhexanoate; ethyl 3-hydroxyhexanoate can be synthesized under similar reaction conditions using ethanol instead of methanol. This method has a short synthetic route and can conveniently and quickly obtain 3-hydroxyhexanoate products; its main problem lies in the source of 3-hydroxyhexanoic acid. Chemical synthesis is still relatively cumbersome, while bio-fermentation can produce 3-hydroxyhexanoic acid, but it is also quite expensive. The esterification of 3-hydroxyhexanoic acid with methanol (or ethanol) requires a long reaction time (~10 hours) and produces a large amount of intermolecular esterification byproducts of 3-hydroxyhexanoic acid itself (Tetrahedron, 1989, 45, 1639-1646).

[0006]

[0007] In summary, the main synthetic methods for 3-hydroxyhexanoates currently involve direct esterification using relatively expensive 3-hydroxyhexanoic acid as a starting material, or multi-step synthesis using n-butyraldehyde, bromine, and acetic acid as raw materials. These methods require expensive raw materials such as 3-hydroxyhexanoic acid or bromine, and generate a large amount of byproducts that are difficult to treat harmlessly, resulting in high treatment costs. Therefore, there is an urgent need to develop novel and efficient synthetic routes for 3-hydroxyhexanoates that not only use inexpensive starting materials but also produce less waste, have a simple and efficient production process, and operate under mild conditions; ideally, they should also produce a series of different 3-hydroxyhexanoate analogs. Summary of the Invention

[0008] The purpose of this invention is to provide a method for synthesizing 3-hydroxyhexanoate from n-butyraldehyde. Using inexpensive and readily available n-butyraldehyde, ketene, and alcohol as raw materials, 3-hydroxyhexanoate is synthesized through reactions such as condensation, depolymerization, and esterification. This method has a novel synthetic route, mild reaction conditions, and inexpensive raw materials, and has promotional value.

[0009] To achieve the above objectives and technical effects, the present invention adopts the following technical solution:

[0010] A method for synthesizing 3-hydroxyhexanoate from n-butyraldehyde, the method comprising the following steps:

[0011] S1: Under the action of Lewis acid catalyst and sulfide auxiliaries, n-butyraldehyde and ketene are condensed to obtain low molecular weight polyester;

[0012] S2: Depolymerization is carried out, and the low molecular weight polyester is converted into β-n-propylpropiolactone intermediate;

[0013] S3: The intermediate reacts with the alcohol to give 3-hydroxyhexanoate.

[0014] The reaction route is shown below:

[0015]

[0016] In the above scheme, the condensation reaction of butyraldehyde and ketene employs a Lewis acid catalyst and a thioether catalyst for synergistic catalysis. The thioether catalyst effectively promotes the dissolution of the Lewis acid, accelerates the reaction, and improves polyester selectivity. β-n-propylpropiolactone is obtained by depolymerizing the low-molecular-weight polyester through scraped-film distillation; the reaction and separation occur simultaneously, providing a rapid and convenient way to obtain β-n-propylpropiolactone. The β-n-propylpropiolactone intermediate can react with different alcohols such as methanol and ethanol, facilitating the synthesis of various 3-hydroxyhexanoate products.

[0017] In this invention, the Lewis acid catalyst in S1 is one or more of zinc chloride, zinc bromide, zinc acetate, zinc butyrate, zinc isobutyrate, zinc acetylacetonate, ferrous chloride, ferric chloride, cobalt dichloride, scandium trifluoromethanesulfonate, calcium acetylacetonate, and copper acetylacetonate; preferably, the amount of the catalyst is 0.1% to 2% of the molar amount of n-butyraldehyde.

[0018] In this invention, the thioether auxiliary in S1 is a thioether and / or a dithioether, preferably one or more of ethylenedithiol dimethyl ether, ethylenedithiol diethyl ether, ethylenedithiol, 1,3-propanedithiol, 1,3-di(methylthio)propane, and 2,9-dithiodecane; preferably, the amount of the thioether auxiliary is 0.1% to 2% of the molar amount of n-butyraldehyde.

[0019] In this invention, the molar ratio of n-butyraldehyde and ketene in S1 is (1.0-1.3):1.0.

[0020] In this invention, the condensation reaction described in S1 is carried out under solvent-containing or solvent-free conditions, preferably under solvent-containing conditions; preferably, the solvent is one or more of benzene, toluene, xylene, low-carbon alkanes, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, dichloromethane, and dichloroethane.

[0021] In this invention, the condensation reaction described in S1 has a reaction temperature of 30–80°C, a reaction pressure of atmospheric pressure, and a reaction time of 2–5 hours.

[0022] In this invention, S2 employs scraped plate distillation depolymerization, which is carried out continuously with top-in and bottom-out flow. The inner surface temperature of the scraper is 120-150℃, the system pressure is 1.0-5.0 hPaA, and the residence time of the polyester on the inner surface of the scraper is 10-20 min.

[0023] In this invention, β-n-propylpropyl lactone is collected above the scraper in S2, and a mixture mainly composed of polyester is collected at the bottom of the scraper. The mixture is then recycled back into the scraper for depolymerization.

[0024] In this invention, the catalyst in the reaction described in S3 is one or more of concentrated sulfuric acid, phosphoric acid, phosphorous acid, nitric acid, methanesulfonic acid, and p-toluenesulfonic acid; preferably, the amount of catalyst used is 0.1% to 2% of the molar amount of β-n-propylpropiolactone.

[0025] In this invention, the reaction described in S3 uses alcohol as the reaction solvent; optionally, excess alcohol is recovered and reused after the reaction is completed.

[0026] In this invention, the reaction pressure in S3 is atmospheric pressure; the reaction temperature is 80-100℃; and the reaction time is 0.5-3.0 hours.

[0027] In this invention, unless otherwise specified, all pressures are gauge pressures.

[0028] Compared with the prior art, the present invention has the following positive effects:

[0029] 1. The raw materials used in this method, n-butyraldehyde and methanol, are inexpensive and readily available. Ketene can be obtained by high-temperature cracking of acetic acid. The synthetic route described in this invention is novel, has a high yield (the total yield can reach up to 86%), and generates almost no waste. Compared with existing methods, it has a significant cost advantage.

[0030] 2. This invention employs a Lewis acid catalyst and a sulfide catalyst to synergistically catalyze the condensation of n-butyraldehyde and ketene. The co-catalyst effectively improves the solubility of the Lewis acid catalyst in the reaction solution, accelerates the reaction, and increases the polyester selectivity (selectivity increases from 87% to 96%).

[0031] 3. Low molecular weight polyester is depolymerized by scraped distillation, and the reaction and separation are carried out simultaneously, which can quickly and conveniently obtain β-n-propylpropiolactone. The polyester has a short residence time on the scraper surface, does not require long-term heating, and produces less by-products such as tar.

[0032] 4. β-n-propylpropiolactone intermediate can react with different alcohols such as methanol and ethanol to conveniently synthesize different 3-hydroxyhexanoate products. Detailed Implementation

[0033] The present invention is described in detail below through embodiments, but the present invention is not limited to the embodiments described below.

[0034] The main raw material information is as follows:

[0035] Butyraldehyde, Wanhua Chemical, 99%; Diethyl ether, toluene, tetrahydrofuran, methyl tert-butyl ether, AR, Aladdin reagent; Zinc acetate, zinc acetylacetone, calcium acetylacetone, ferrous chloride, ammonium bicarbonate, Bailingwei reagent, purity 98-99%; 1,3-Di(methylthio)propane, ethylenedithiol dimethyl ether, 2,9-dithiodecane, Maclean, 98%.

[0036] p-Toluenesulfonic acid, 99%, Inokai reagent;

[0037] Ethanol, methanol, Xilong reagent, AR.

[0038] The gas chromatography test conditions of this invention are as follows:

[0039] Instrument model: Agilent 7890B; Column: HP-Innowax capillary column (30m × 0.30mm × 0.25μm); Initial temperature 80℃, increased to 120℃ at a rate of 5℃ / min; then increased to 280℃ at a rate of 20℃ / min and held for 5 min. Carrier gas: high-purity nitrogen, split ratio 40:1, split flow rate 45mL / min. Carrier gas saving: 20mL / min, initial waiting time 2min. Injection temperature 280℃, detector: FID, detector temperature 280℃, air flow rate 350mL / min, hydrogen flow rate 35mL / min, make-up gas flow rate 30mL / min, injection volume 0.2μL.

[0040] Example 1

[0041] Zinc acetate catalyzes the condensation of n-butyraldehyde and ketene.

[0042] A 2L pressure-resistant glass-jacketed reactor was sealed at room temperature and pressurized with 0.3MPa nitrogen for 30 minutes. The pressure inside the reactor did not decrease, indicating good sealing. The reactor was then disassembled, and the following ingredients were added: n-butyraldehyde (165.84g, 2.3mol), zinc acetate (0.84g, 4.6mmol), 1,3-di(methylthio)propane (0.94g, 6.9mmol), and toluene (200mL). The reactor was resealed, and nitrogen was purged three times at 0.2MPa each time. Finally, the pressure inside the reactor was reduced to atmospheric pressure. The reactor was then stirred and heated. When the temperature inside the reactor reached 60°C, ketene gas was introduced into the reactor from a ketene generator at a rate of 0.258L / min. The gas was fed at atmospheric pressure for 3 hours, totaling 46.37L (2.07mol). A small amount of ketene gas was not absorbed by the reaction solution and was discharged into the waste gas absorption tank (containing sodium hydroxide aqueous solution) via the gas phase pipeline. After the ketene feed was complete, stirring and constant temperature reaction continued for 1 hour. Sampling was performed using a dual-valve sampling method. The sample was immediately added to an ether-ammonium bicarbonate two-phase solution (50 / 50, v / v). The sample was shaken evenly in a fume hood, and the upper organic phase was taken for HPLC analysis. The conversion rate of the raw material n-butyraldehyde was 85%, and the selectivity of the target product polyester was 94%.

[0043] Example 2

[0044] Zinc acetylacetonate catalyzes the condensation of n-butyraldehyde and ketene.

[0045] A 2L pressure-resistant glass-jacketed reactor was used. The raw material n-butyraldehyde (165.84g, 2.3mol), catalyst zinc acetylacetone (0.61g, 3.6mmol), co-catalyst 1,3-di(methylthio)propane (0.94g, 6.9mmol), and solvent toluene (200mL) were added to the reactor in air. The reactor was resealed, and nitrogen was purged three times at 0.3MPa each time. Finally, the pressure inside the reactor was reduced to atmospheric pressure. The reactor was then stirred and heated. When the temperature inside the reactor reached 40°C, ketene gas was introduced into the reactor. The ketene gas was supplied by a ketene generator at a feed rate controlled at 0.258L / min. The atmospheric pressure gas phase feed lasted for 3 hours, with a total feed volume of 46.37L (2.07mol). A small amount of ketene gas was not completely absorbed by the reaction liquid and was discharged into the waste gas absorption tank via the gas phase pipeline. After the ketene feed was completed, the mixture was stirred and reacted at a constant temperature for 2 hours. Samples were then taken, and the conversion rate of n-butyraldehyde was analyzed by HPLC. A dual-valve sampling method was used. The sample was immediately added to a mixture of diethyl ether and ammonium bicarbonate (50 / 50, v / v), and after thorough shaking, the upper organic phase was taken for HPLC analysis. The conversion rate of the n-butyraldehyde feedstock was 76%, and the selectivity of the target product (polyester) was 95%.

[0046] Example 3

[0047] Zinc acetylacetonate catalyzes the condensation of n-butyraldehyde and ketene.

[0048] A 2L pressure-resistant glass-jacketed reactor was used. The raw material n-butyraldehyde (266.8g, 3.7mol), catalyst zinc acetylacetone (9.75g, 37.0mmol), co-catalyst 1,3-di(methylthio)propane (7.56g, 55.5mmol), and solvent toluene (400mL) were added to the reactor in air. The reactor was resealed, and nitrogen was purged three times at 0.3MPa each time. Finally, the pressure inside the reactor was reduced to atmospheric pressure. The reactor was then stirred and heated. When the temperature inside the reactor reached 60℃, ketene gas was introduced into the reactor. The ketene gas was supplied by a ketene generator, with a feed rate controlled at 0.262L / min. The gas phase was fed at atmospheric pressure for 5 hours, totaling 78.74L (3.52mol). A small amount of ketene gas was not completely absorbed by the reaction liquid and was discharged into the waste gas absorption tank via the gas phase pipeline. After the ketene feed was completed, the mixture was stirred and kept at a constant temperature for 1 hour. Samples were taken and the conversion rate of n-butyraldehyde was analyzed by HPLC. A dual-valve sampling method was used. The sample was immediately added to a mixture of diethyl ether and ammonium bicarbonate (50 / 50, v / v) after being taken out and shaken evenly. The upper organic phase was then taken for HPLC analysis. The conversion rate of n-butyraldehyde was 93%, and the selectivity of polyester was 96%.

[0049] Example 4

[0050] Calcium acetylacetonate catalyzes the condensation of n-butyraldehyde and ketene.

[0051] A 2L pressure-resistant glass-jacketed reactor was used. First, the following were added: n-butyraldehyde (252.37g, 3.5mol), calcium acetylacetonate catalyst (16.72g, 70.0mmol), dimethyl ethylene dithiol ether co-catalyst (8.56g, 70.0mmol), and methyl tert-butyl ether solvent (350mL). The reactor was resealed, and nitrogen was purged three times at 0.3MPa each time. Finally, the pressure inside the reactor was reduced to atmospheric pressure. The reactor was then stirred and heated. When the temperature inside the reactor reached 30°C, ketene gas was introduced into the reactor. The ketene gas was generated in situ by a ketene generator, with a feed rate controlled at 0.436L / min. The gas phase was fed at atmospheric pressure for 3 hours, totaling 78.4L (1.98mol). A small amount of ketene gas was not completely absorbed by the reaction liquid and was discharged into the waste gas absorption tank via the gas phase pipeline. After the ketene was fed, stirring and constant temperature reaction were continued for 2 hours. A dual-valve sampling method was used. After the sample was taken out, it was immediately added to the ether-ammonium bicarbonate mixture (50 / 50, v / v). After shaking and homogenization, the upper organic phase was taken for HPLC analysis. The conversion rate of the raw material n-butyraldehyde was 99%, and the selectivity of the target product polyester was 94%.

[0052] Example 5

[0053] Ferrous chloride catalyzes the condensation of n-butyraldehyde and ketene.

[0054] A 2L pressure-resistant glass-jacketed reactor was used. The raw material n-butyraldehyde (158.63g, 2.2mol), catalyst ferrous chloride (1.39g, 11.0mmol), 1,3-dimethoxypropane (2.35g, 13.2mmol), and solvent tetrahydrofuran (200mL) were added to the reactor in air. The reactor was resealed, and nitrogen was purged three times at 0.2MPa each time. Finally, the pressure inside the reactor was reduced to atmospheric pressure. The reactor was then stirred and heated. When the temperature inside the reactor reached 40°C, ketene gas was introduced into the reactor. The ketene gas was supplied by a ketene generator at a feed rate controlled at 0.164L / min. The gas was introduced stably at atmospheric pressure for 4 hours, with a total feed of 39.42L (1.76mol). A small amount of ketene gas was not completely absorbed by the reaction liquid and was discharged into the waste gas absorption tank via the gas phase pipeline. After the ketene feed was completed, the mixture was stirred and kept at a constant temperature for 2 hours. Samples were taken and the conversion rate of n-butyraldehyde was analyzed by HPLC. A dual-valve sampling method was used. The sample was immediately added to a mixture of diethyl ether and ammonium bicarbonate (50 / 50, v / v), and after shaking to homogenize, the upper organic phase was taken for HPLC analysis. The conversion rate of the raw material n-butyraldehyde was 78%, and the selectivity of the target product polyester was 94%. After the condensation reaction was completed, nitrogen was used to fully replace the residual gas in the reactor. Then, a 10% ammonium bicarbonate aqueous solution was added to the reactor to quench the condensation reaction. After the reaction liquid separated into phases, the organic phase was washed with water. Subsequently, the organic phase was directly subjected to distillation to separate toluene and a small amount of unconverted n-butyraldehyde (70-80℃, 300-400Pa). The low-molecular-weight polyester obtained from the bottom of the distillation column was directly fed into the scraper for distillation and depolymerization.

[0055] Example 6

[0056] Low molecular weight polyester scraper distillation depolymerization of β-n-propylpropiolactone intermediate (raw material from Example 3).

[0057] Low molecular weight polyester was depolymerized using a falling film scraper reactor with an inner surface area of ​​0.2 m². 2 During depolymerization, the scraper heating jacket is first turned on. Once the scraper raises the internal temperature to approximately 150°C, the feed pump is turned on to feed 500g of crude low-molecular-weight polyester at a feed rate of 20.0 mL / min, resulting in a liquid film thickness of 1 mm. The residence time of the crude polyester in the scraper is 10 min, and the system pressure is 200 PaA. The feed liquid flows from top to bottom. β-n-propylpropiolactone is collected from the top of the scraper, cooled, and then enters the product collection tank. The bottom of the scraper collects a mixture mainly composed of unconverted low-molecular-weight polyester. This mixture is circulated by the pump and then pumped back into the scraper for depolymerization. After 21 hours of continuous operation, the low-molecular-weight polyester is essentially completely depolymerized, yielding 460g of β-n-propylpropiolactone, a yield of 92%.

[0058] Example 7

[0059] Low molecular weight polyester scraper distillation depolymerization of β-n-propylpropiolactone intermediate (raw material from Example 4).

[0060] Low molecular weight polyester was depolymerized using a falling film scraper reactor with an inner surface area of ​​0.2 m². 2 During depolymerization, the scraper heating jacket is first turned on. Once the scraper raises the internal temperature to approximately 140°C, the feed pump is turned on to feed 500g of crude low-molecular-weight polyester at a feed rate of 15.0 mL / min, resulting in a liquid film thickness of 1.1 mm. The residence time of the crude polyester in the scraper is 15 min, and the system pressure is 100 PaA. The feed liquid flows from top to bottom. β-n-propylpropiolactone is collected from the top of the scraper, cooled, and then enters the product collection tank. The bottom of the scraper collects a mixture mainly composed of unconverted low-molecular-weight polyester. This mixture is circulated by the pump and then pumped back into the scraper for depolymerization. After 21 hours of continuous operation, the low-molecular-weight polyester is essentially completely depolymerized, yielding 471g of β-n-propylpropiolactone, a yield of 91%.

[0061] Example 8

[0062] β-n-propylpropiolactone and methanol were esterified to synthesize methyl 3-hydroxyhexanoate (raw material from Example 6).

[0063] Under a nitrogen atmosphere, anhydrous methanol (416.6 g, 13.0 mol) and p-toluenesulfonic acid (1.12 g, 6.5 mmol) were added sequentially to a 1 L three-necked flask equipped with a magnetic stirrer, a constant-pressure dropping funnel, and a reflux condenser at room temperature. Stirring was started to completely dissolve the p-toluenesulfonic acid. The flask was then placed in a 90 °C oil bath. After the reaction solution temperature stabilized, β-n-propylpropiolactone (148.4 g, 1.3 mol) was added dropwise to the reaction solution, completing the addition after 1.0 h. After the addition was complete, the reaction was continued with rapid stirring for 1.5 h. GC analysis showed that the starting material β-n-propylpropiolactone reacted completely. The reaction flask was removed from the oil bath and cooled to room temperature. A certain amount of sodium hydroxide methanol solution (containing 6.5 mmol of sodium hydroxide) was added to neutralize the catalyst p-toluenesulfonic acid. The resulting reaction solution was then subjected to vacuum distillation to separate methanol and the target product, yielding 184.3 g of methyl 3-hydroxyhexanoate, with a yield of 97% (calculated as β-n-propylpropiolactone).

[0064] Example 9

[0065] β-n-propylpropiolactone and ethanol were esterified to synthesize ethyl 3-hydroxyhexanoate (raw materials from Example 7).

[0066] Under a nitrogen atmosphere, anhydrous ethanol (419.2 g, 9.1 mol) and p-toluenesulfonic acid (4.48 g, 26.0 mmol) were added sequentially to a 1 L three-necked flask equipped with a magnetic stirrer, a constant-pressure dropping funnel, and a reflux condenser at room temperature. Stirring was initiated until the p-toluenesulfonic acid was completely dissolved. The flask was then placed in an 80 °C oil bath. After the reaction solution temperature stabilized, β-n-propylpropiolactone (148.4 g, 1.3 mol) was added dropwise over 1.0 h. After the addition was complete, the reaction was continued with rapid stirring for another 2.0 h. GC analysis showed that the starting material β-n-propylpropiolactone reacted completely. The reaction flask was removed from the oil bath and cooled to room temperature. A certain amount of sodium hydroxide ethanol solution (containing 30.0 mmol of sodium hydroxide) was added to neutralize the catalyst p-toluenesulfonic acid. The resulting reaction solution was then subjected to vacuum distillation to separate ethanol and the target product in sequence, yielding 199.9 g of ethyl 3-hydroxyhexanoate, with a yield of 96% (calculated as β-n-propylpropiolactone).

[0067] Comparative Example 1

[0068] Compared with Example 1, zinc acetylacetonate catalyzes the condensation of n-butyraldehyde and ketene without a co-catalyst.

[0069] A 2L pressure-resistant glass-jacketed reactor was used. Butyraldehyde (165.84g, 2.3mol), zinc acetylacetonate (3.03g, 11.5mmol), and benzene (160mL) were added to the reactor in air. No co-catalyst sulfide was added. The reactor was resealed, and nitrogen was introduced three times at 0.3MPa each time, finally reducing the pressure to atmospheric pressure. The reactor was then stirred and heated. When the temperature reached 40°C, ketene gas was introduced from a ketene generator at a feed rate of 0.193L / min over 4 hours at atmospheric pressure, totaling 46.37L (2.07mol). A small amount of ketene gas, not completely absorbed by the reaction liquid, was discharged into a waste gas absorption tank via a gas phase pipeline. After the ketene feed was complete, stirring and constant temperature reaction continued for 2 hours. Samples were taken, and the conversion rate of butyraldehyde was analyzed by HPLC. A dual-valve sampling method was used. After the sample was taken out, it was immediately added to a mixture of diethyl ether and ammonium bicarbonate (50 / 50, v / v). After shaking and homogenization, the upper organic phase was taken for HPLC analysis. The conversion rate of the raw material n-butyraldehyde was 65%, and the selectivity of the target product polyester was 87%.

[0070] Comparative Example 2

[0071] Direct esterification of 3-hydroxyhexanoic acid to synthesize ethyl 3-hydroxyhexanoate (Reference: Tetrahedron, 1989, 45, 1639-1646).

[0072] Under a nitrogen atmosphere, anhydrous ethanol (230.3 g, 5.0 mol), p-toluenesulfonic acid (0.86 g, 5.0 mmol), 3-hydroxyhexanoic acid (66.1 g, 0.5 mol), and cyclohexane (100 mL) were added sequentially to a 1 L three-necked flask equipped with a magnetic stirrer, reflux condenser, and water separator at room temperature. Stirring was initiated to completely dissolve the p-toluenesulfonic acid. The flask was then placed in a 70 °C oil bath, and cyclohexane reflux was applied to remove water and promote the esterification reaction. After rapid stirring for 10.0 h, GC analysis showed that the 3-hydroxyhexanoic acid reacted completely. The reaction flask was removed from the oil bath and cooled to room temperature. A certain amount of sodium hydroxide ethanol solution (containing 5.0 mmol of sodium hydroxide) was added to neutralize the p-toluenesulfonic acid catalyst. The resulting reaction solution was then subjected to vacuum distillation to separate ethanol and the target product, yielding 66.5 g of ethyl 3-hydroxyhexanoate, with a yield of 83% (based on 3-hydroxyhexanoic acid).

Claims

1. A method for synthesizing 3-hydroxyhexanoate from n-butyraldehyde, characterized in that, The method includes the following steps: S1: Under the action of Lewis acid catalyst and sulfide auxiliaries, n-butyraldehyde and ketene are condensed to obtain low molecular weight polyester; S2: Depolymerization occurs, and the low-molecular-weight polyester is converted into... - n-Propylpropiolactone intermediate; S3: - The reaction of n-propylpropiolactone intermediate with an alcohol yields 3-hydroxyhexanoate; Wherein, the Lewis acid catalyst described in S1 is one or more of zinc chloride, zinc bromide, zinc acetate, zinc butyrate, zinc isobutyrate, zinc acetylacetonate, ferrous chloride, ferric chloride, cobalt dichloride, scandium trifluoromethanesulfonate, calcium acetylacetonate, and copper acetylacetonate; Wherein, the sulfide auxiliary in S1 is sulfide and / or disulfide; S2 is depolymerized by scraped distillation, with the inner surface temperature of the scraper being 120-150℃.

2. The method according to claim 1, characterized in that, The amount of Lewis acid catalyst mentioned in S1 is 0.1% to 2% of the molar amount of n-butyraldehyde.

3. The method according to claim 1 or 2, characterized in that, The thioether additive in S1 is one or more of ethylene dithiol dimethyl ether, ethylene dithiol diethyl ether, 1,3-di(methylthio)propane, and 2,9-dithiodecane.

4. The method according to claim 3, characterized in that, The amount of the sulfide auxiliary agent mentioned in S1 is 0.1% to 2% of the molar amount of n-butyraldehyde.

5. The method according to claim 1, characterized in that, The molar ratio of n-butyraldehyde and ketene in S1 is (1.0~1.3):1.

0.

6. The method according to claim 1, characterized in that, The condensation reaction described in S1 is carried out under solvent- or solvent-free conditions.

7. The method according to claim 6, characterized in that, The condensation reaction described in S1 is carried out in the presence of a solvent; The solvent is one or more selected from benzene, toluene, xylene, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, dichloromethane, and dichloroethane.

8. The method according to claim 1, characterized in that, The condensation reaction described in S1 has a reaction temperature of 30~80℃, a reaction pressure of atmospheric pressure, and a reaction time of 2~5 hours.

9. The method according to claim 1, characterized in that, The scraper distillation and depolymerization described in S2 is carried out in a top-in, bottom-out, continuous manner, with a system pressure of 1.0-5.0 hPaA and a residence time of the polyester on the inner surface of the scraper of 10-20 min.

10. The method according to claim 1, characterized in that, S2 above the scraper extracts - n-Propylpropyl lactone, the mixture mainly composed of polyester is collected from the bottom of the scraper and recycled back into the scraper for depolymerization.

11. The method according to claim 1, characterized in that, The catalyst in the reaction described in S3 is one or more of concentrated sulfuric acid, phosphoric acid, phosphorous acid, nitric acid, methanesulfonic acid, and p-toluenesulfonic acid.

12. The method according to claim 11, characterized in that, The amount of catalyst used in S3 is: -0.1% to 2% of the molar amount of n-propylpropiolactone.

13. The method according to claim 1, characterized in that, The reaction described in S3 uses an alcohol as the reaction solvent; Optionally, the excess alcohol is recovered and reused after the reaction is completed; And / or, the reaction described in S3 is carried out at atmospheric pressure; the reaction temperature is 80~100℃; and the reaction time is 0.5~3.0 hours.

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