A continuous preparation apparatus and method for ethyl 6-chloro-6-oxohexanoate

Abstract

This invention belongs to the field of organic synthesis and relates to a continuous preparation apparatus and method for ethyl 6-chloro-6-oxohexanoate. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor includes at least two sequentially connected reaction sections. The first reaction section is equipped with a raw material inlet. Each reaction section is followed by a hydrogen chloride gas-liquid separator, with a thionyl chloride inlet located between adjacent reaction sections. The continuous preparation apparatus and method for ethyl 6-chloro-6-oxohexanoate provided by this invention offers mild conditions, high yield, efficient recovery of sulfur dioxide and hydrogen chloride gas, safety, reliability, environmental friendliness, reduced environmental pollution, and low cost.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and specifically relates to a continuous preparation apparatus and method for ethyl 6-chloro-6-oxohexanoate. Background Technology

[0002] Alpha lipoic acid (ALA) is a coenzyme found in mitochondria and belongs to the B vitamins. It can eliminate free radicals that accelerate aging and cause disease. After being absorbed by the intestines, ALA enters cells. Due to its combination of fat-soluble and water-soluble properties, it can travel freely throughout the body and reach any cellular site, making it a versatile antioxidant that provides comprehensive health benefits.

[0003] Ethyl 6-chloro-6-oxohexanoate is the main raw material for the synthesis of ethyl 6,8-dichlorooctanoate, which is an important intermediate in the synthesis of lipoic acid. Currently, the industrial synthesis of ethyl 6-chloro-6-oxohexanoate mainly involves the chlorination of monoethyl adipic acid with thionyl chloride. However, this method has a major problem: it generates large amounts of sulfur dioxide and hydrogen chloride gas during the reaction. Sulfur dioxide is one of the six environmental indicators strictly controlled by the government, and its treatment is difficult. The current main treatment method is alkaline absorption. However, alkaline absorption involves converting sulfur dioxide gas into a mixture of sodium sulfite and sodium chloride using an alkaline solution. This method has limited sales volume, and because the resulting aqueous solution must be concentrated to obtain the ammonium sulfite and sodium chloride mixture, the production process is energy-intensive and costly. To reduce air pollution, CN101125815A uses bis(trichloromethyl)carbonate as a chlorinating agent to react with monoethyl adipic acid. While this method can reduce sulfur dioxide generation during the reaction, it requires high reaction temperatures and long reaction times, increasing production costs. Furthermore, the hydrogen chloride and carbon dioxide gases generated during the reaction are not treated in any way. Most importantly, phosgene may be generated during the reaction; phosgene is a highly carcinogenic gas that causes significant atmospheric pollution. In addition, direct emission of hydrogen chloride gas into the atmosphere would also cause environmental pollution and waste of resources. Summary of the Invention

[0004] The primary objective of this invention is to provide a continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate with mild reaction conditions, high product yield, and efficient recovery of sulfur dioxide and hydrogen chloride gas.

[0005] A second objective of the present invention is to provide a method for continuously preparing ethyl 6-chloro-6-oxohexanoate using the above-described continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate.

[0006] Specifically, the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate provided by the present invention includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor includes at least two reaction sections connected in sequence. The first reaction section is provided with a raw material inlet. After each reaction section, a hydrogen chloride gas-liquid separator is provided, and after the hydrogen chloride gas-liquid separator located between two adjacent reaction sections, a thionyl chloride inlet is provided.

[0007] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided by the present invention is carried out in the above-mentioned continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate. Specifically, the continuous preparation method of ethyl 6-chloro-6-oxohexanoate includes continuously feeding reaction solution I and reaction solution II into the first reaction section of a pipeline reactor from the raw material inlet for chlorination reaction, and continuously feeding reaction solution III into the remaining reaction sections of the pipeline reactor from the thionyl chloride inlet for further chlorination reaction. Reaction solution I is a solution containing monoethyl adipate and an amide catalyst, and reaction solutions II and III are both thionyl chloride. During the chlorination reaction, a back pressure valve is used to control the pressure in the pipeline reactor so that the sulfur dioxide produced by the chlorination reaction is in a liquid state and the hydrogen chloride is in a gaseous state. Simultaneously, a hydrogen chloride gas-liquid separator is used to separate and remove the hydrogen chloride gas produced by the chlorination reaction from the reaction system. After the reaction is completed, the reaction solution is depressurized through the back pressure valve, and the sulfur dioxide changes from a liquid state to a gaseous state. Then, a sulfur dioxide gas-liquid separator is used to separate the sulfur dioxide to obtain crude ethyl 6-chloro-6-oxohexanoate.

[0008] Although pipeline reactors have advantages such as low backmixing, high volumetric efficiency, and high heat exchange efficiency, the preparation process of ethyl 6-chloro-6-oxohexanoate is usually not carried out using pipeline reactors, but rather batch reactors are chosen. This is because the preparation process of ethyl 6-chloro-6-oxohexanoate generates a large amount of gas. As is known to those skilled in the art, pipeline reactors are generally not used in chemical reactions that generate a large amount of gas due to their limited space and difficulty in venting. However, this invention employs a multi-stage pipeline reactor, which allows for the batch and staged addition of thionyl chloride. This effectively avoids the instantaneous generation of massive amounts of hydrogen chloride gas affecting residence time and causing side reactions. Furthermore, a hydrogen chloride gas-liquid separator is cleverly installed after each reaction stage to continuously separate the gas generated during the reaction and promote its progress. Based on this, a back pressure valve controls the pressure in the reaction system, maintaining a certain pressure in the reaction stage before the back pressure valve so that sulfur dioxide is in a liquid state and hydrogen chloride is in a gaseous state, allowing the hydrogen chloride gas to be separated by the hydrogen chloride gas-liquid separator. The processing stage after the back pressure valve is in a depressurized state, so that sulfur dioxide is in a gaseous state and ethyl 6-chloro-6-oxohexanoate is in a liquid state, allowing the sulfur dioxide gas to be separated by the sulfur dioxide gas-liquid separator.

[0009] This invention employs a gas-liquid separator to collect and add thionyl chloride in batches, enabling the timely separation and recovery of hydrogen chloride gas generated during the reaction. This promotes further reaction between the remaining ethyl adipic acid and thionyl chloride, ensuring complete reaction of ethyl adipic acid even with a relatively low thionyl chloride dosage. This achieves a continuous reaction process with high product yield. Furthermore, the byproduct gases are collected in a gentler manner throughout the continuous reaction, avoiding the boiling-up phenomenon present in batch reactions and increasing the safety of the reaction process.

[0010] In summary, the continuous preparation apparatus and method for ethyl 6-chloro-6-oxohexanoate provided by this invention have mild conditions, high yield, and achieve efficient recovery of sulfur dioxide and hydrogen chloride gas. It is safe, reliable, environmentally friendly, reduces environmental pollution, and has low cost.

[0011] In a preferred embodiment, the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate also includes an acid-binding agent inlet between the sulfur dioxide gas-liquid separator and the vacuum distillation apparatus. Correspondingly, the continuous preparation method for ethyl 6-chloro-6-oxohexanoate further includes adding an acid-binding agent to the crude ethyl 6-chloro-6-oxohexanoate before vacuum distillation. At this time, the acid-binding agent can remove residual sulfur dioxide and hydrogen chloride, further reducing the impact of a small amount of residual sulfur dioxide and hydrogen chloride gas on the equipment and environment in subsequent processing, thus more effectively achieving the environmental friendliness of the reaction and further reducing production costs. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of a continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate provided by the present invention. Detailed Implementation

[0013] like Figure 1 As shown, the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate provided by the present invention includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor includes at least two reaction sections connected in sequence. The first reaction section is provided with a raw material inlet. After each reaction section, a hydrogen chloride gas-liquid separator is provided, and after the hydrogen chloride gas-liquid separator located between two adjacent reaction sections, a thionyl chloride inlet is provided.

[0014] In this invention, to prevent material from adhering inside the pipeline reactor after prolonged operation and to extend the service life of the pipeline reactor, the pipeline reactor is preferably made of tetrafluoroethylene (PTFE) pipe. The diameter φ of the pipeline reactor is preferably 3–50 mm, such as 3 mm, 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, or any value between them; the total length is preferably 100–2000 mm, such as 100 mm, 200 mm, 300 mm, 400 mm, 500 mm, 600 mm, 800 mm, 1000 mm, 1200 mm, 1400 mm, 1600 mm, 1800 mm, 2000 mm, or any value between them. Setting the diameter and total length of the pipeline reactor within the above ranges is more conducive to reducing backmixing and improving heat exchange efficiency, thereby further improving the yield and purity of ethyl 6-chloro-6-oxohexanoate.

[0015] In this invention, the pipeline reactor comprises at least two reaction sections, specifically 2, 3, 4, 5, 6, 8, 9, or 10 sections. Considering the simplicity of the structural design and the ease of venting the reaction gases, 2 to 5 sections are preferred. Furthermore, the lengths of the different reaction sections of the pipeline reactor are preferably consistent. This ensures that the residence time of the material in each reaction section is essentially the same, and the amount of thionyl chloride consumed and the amount of hydrogen chloride produced are also approximately similar. This results in minimal system pressure fluctuations, achieving ideal reaction results and a higher product yield.

[0016] In one specific implementation, such as Figure 1As shown, the pipeline reactor comprises three reaction sections along the material flow direction: reaction section I, reaction section II, and reaction section III. The first reaction section (reaction section I) is equipped with a raw material inlet for introducing ethyl adipic acid and thionyl chloride. This inlet can be configured as one, in which case ethyl adipic acid and thionyl chloride are introduced from the same inlet; or it can be configured as two, in which case ethyl adipic acid and thionyl chloride are introduced from different inlets. A hydrogen chloride gas-liquid separator is installed after each reaction section to promptly separate the gases produced during the reaction. The first reaction section of the pipeline reactor has a raw material inlet, while the remaining reaction sections have thionyl chloride inlets. Ethyl adipic acid is added only from the first reaction section, while thionyl chloride needs to be added from each reaction section (preferably in the same amount from each section). This not only promotes the full reaction of ethyl adipic acid and thionyl chloride but also ensures a gentler reaction process, preventing boiling over. Furthermore, the thionyl chloride inlet is located after the hydrogen chloride gas-liquid separator, that is, the hydrogen chloride gas in the reaction system is removed as much as possible before thionyl chloride is added. This is more conducive to improving the yield and purity of ethyl 6-chloro-6-oxohexanoate.

[0017] It should be noted that in this invention, "Ⅰ", "Ⅱ" and "Ⅲ" are merely used to distinguish the same components located in different positions for ease of description, and have no other special meaning.

[0018] In a preferred embodiment, the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate further includes a vacuum distillation apparatus and a condenser. The vacuum distillation apparatus is connected to the liquid outlet of a sulfur dioxide gas-liquid separator, and the condenser is connected to the gas outlet of the sulfur dioxide gas-liquid separator. In this way, high-purity ethyl 6-chloro-6-oxohexanoate can be obtained by vacuum distillation, and unreacted thionyl chloride can be recovered and reused, causing almost no air pollution and reducing production costs and environmental pressure.

[0019] In a preferred embodiment, an acid-binding agent inlet is provided between the sulfur dioxide gas-liquid separator and the vacuum distillation unit. At this time, a small amount of acid-binding agent can be introduced through the acid-binding agent inlet to remove the sulfur dioxide and hydrogen chloride remaining in the reaction products, thereby further avoiding the leakage of harmful by-products and improving the green environmental protection.

[0020] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided by the present invention is carried out in the above-mentioned continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate.

[0021] Specifically, the continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided by the present invention includes continuously feeding reaction solution I and reaction solution II into the first reaction section of a pipeline reactor from the raw material inlet for chlorination reaction, and continuously feeding reaction solution III into the remaining reaction sections of the pipeline reactor from the thionyl chloride inlet for chlorination reaction. The reaction solution I is a solution containing monoethyl adipate, and the reaction solutions II and III are both thionyl chloride. During the chlorination reaction, the pressure in the pipeline reactor is controlled by a back pressure valve so that the sulfur dioxide produced by the chlorination reaction is in a liquid state and the hydrogen chloride is in a gaseous state. At the same time, the hydrogen chloride gas produced by the chlorination reaction is separated and removed from the reaction system by a hydrogen chloride gas-liquid separator. After the reaction is completed, the reaction solution is depressurized through the back pressure valve, and the sulfur dioxide changes from a liquid state to a gaseous state. Then, the sulfur dioxide is separated by a sulfur dioxide gas-liquid separator to obtain crude ethyl 6-chloro-6-oxohexanoate.

[0022] In this invention, the preferred mass ratio of monoethyl adipic acid to the amide catalyst in reaction solution I is 1:(1‰ to 4‰), such as 1:1‰, 1:2‰, 1:3‰, 1:4‰, or any value between them. Specific examples of the amide catalyst include, but are not limited to, at least one of N,N-dimethylformamide and dimethylacetamide.

[0023] In this invention, the flow rate of reaction solution I is preferably 1–30 mL / min, more preferably 1, 3, 5, 8, 10, 12, 15, 17, 20, 22, 25, 28, 30 mL / min or any value between them. Both reaction solutions II and III are thionyl chloride (SOCl2). The flow rate of reaction solution II is preferably 0.5–10 mL / min, such as 0.5, 2, 4, 6, 8, 10 mL / min or any value between them. The flow rate of reaction solution III is preferably the same as that of reaction solution II. This maintains the overall system pressure at a stable level, prevents backflow of the reaction solution, achieves the desired reaction effect, and further improves the product yield.

[0024] In this invention, the chlorination reaction conditions are required not only to allow ethyl adipic acid and thionyl chloride to react and form ethyl 6-chloro-6-oxohexanoate, but also to ensure that the generated sulfur dioxide is in a liquid state and the hydrogen chloride is in a gaseous state. Specifically, the reaction temperature is preferably 20–50°C, such as 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, or any value between them; the reaction pressure is preferably 0.5–1.2 MPa, such as 0.5 MPa, 0.6 MPa, 0.7 MPa, 0.8 MPa, 0.9 MPa, 1.0 MPa, 1.1 MPa, 1.2 MPa, or any value between them. In this invention, all reaction pressures refer to gauge pressure.

[0025] In a preferred embodiment, the continuous preparation method of ethyl 6-chloro-6-oxohexanoate further includes adding an acid-binding agent to the crude ethyl 6-chloro-6-oxohexanoate, followed by vacuum distillation to obtain refined ethyl 6-chloro-6-oxohexanoate; and / or, the method further includes condensing and recovering gaseous sulfur dioxide. The condensation temperature is preferably -20 to -10°C, such as -20°C, -15°C, -12°C, -10°C, or any value between them. Treatment with an acid-binding agent can adsorb and remove residual sulfur dioxide and hydrogen chloride from the reaction product, further reducing the content of harmful substances in ethyl 6-chloro-6-oxohexanoate. The acid-binding agent can be any existing substance capable of absorbing sulfur dioxide and hydrogen chloride, specific examples including but not limited to at least one of pyridine, 2-methylpyridine, and triethylamine. The preferred amount of the acid-binding agent is 0.2% to 1% of the mass of ethyl adipic acid fed into the reactor, such as 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, or any value between these values. Vacuum distillation can separate ethyl 6-chloro-6-oxohexanoate from impurities, improving the purity of ethyl 6-chloro-6-oxohexanoate, and recovering unreacted thionyl chloride. The fraction obtained from the vacuum distillation at a vacuum of 2 mmHg and a temperature of 85–90 °C is the pure ethyl 6-chloro-6-oxohexanoate.

[0026] The present invention will be described in detail below through embodiments.

[0027] Example 1

[0028] like Figure 1 As shown, the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this embodiment includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor comprises three reaction sections of equal length connected in sequence (i.e., reaction section I, reaction section II, and reaction section III). The first reaction section (reaction section I) is equipped with a raw material inlet (the raw material inlet is connected to a raw material feed pump, the same below). A hydrogen chloride gas-liquid separator I is installed between reaction section I and reaction section II. A hydrogen chloride gas-liquid separator II is installed between reaction section II and reaction section III. A hydrogen chloride gas-liquid separator III is installed between reaction section III and the back pressure valve. A thionyl chloride inlet (connected to a thionyl chloride feed pump, the same below) is installed after hydrogen chloride gas-liquid separator I and hydrogen chloride gas-liquid separator II. The pipeline reactor is a tetrafluoroethylene pipeline with a diameter φ of 3 mm and a total length of 1200 mm. The liquid outlet of the sulfur dioxide gas-liquid separator is connected to a vacuum distillation unit (not shown), and the gas outlet is connected to a condenser (not shown). An acid-binding agent inlet is provided between the sulfur dioxide gas-liquid separator and the vacuum distillation unit (the acid-binding agent inlet is connected to an acid-binding agent feed pump, the same below).

[0029] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided in this embodiment includes the following steps:

[0030] Reaction solution I (a solution containing monoethyl adipate prepared by mixing monoethyl adipate and N,N-dimethylformamide (DMF) at a mass ratio of 1:4‰) and reaction solution II (thionyl chloride) were continuously introduced into the first reaction section of the pipeline reactor at flow rates of 17 mL / min and 2.7 mL / min, respectively. Reaction solution III (thionyl chloride) was continuously introduced into the remaining reaction sections of the pipeline reactor at a flow rate of 2.7 mL / min from the thionyl chloride inlet to continue the reaction. The reaction temperature was set at 40℃, and the pressure of the pipeline reactor was controlled at approximately 0.8 MPa by adjusting the back pressure valve to prevent the reaction solution from becoming too hot or too cold. The hydrogen chloride gas can overflow through the hydrogen chloride gas-liquid separator. The hydrogen chloride gas produced by the chlorination reaction is continuously separated and removed from the reaction system. After the chlorination reaction products flow through the back pressure valve, the system pressure becomes atmospheric pressure. Due to the pressure change, the sulfur dioxide in the reaction system changes from liquid to gas. When the material enters the sulfur dioxide gas-liquid separator, the sulfur dioxide gas in the material is separated from the ethyl 6-chloro-6-oxohexanoate liquid. The sulfur dioxide gas is condensed into liquid in the condenser and thus separated out of the system. The condensation temperature in the condenser is -15℃, while the ethyl 6-chloro-6-oxohexanoate liquid continues to the next step of the operation. The acid-binding agent (2-methylpyridine) was added from the acid-binding agent inlet at a flow rate of 0.17 mL / min. The liquid containing ethyl 6-chloro-6-oxohexanoate from the sulfur dioxide gas-liquid separator then entered a vacuum distillation apparatus and was distilled under vacuum at a vacuum degree of 2 mmHg. The fraction collected at a temperature of 85-90℃ was the pure ethyl 6-chloro-6-oxohexanoate.

[0031] After equilibration for 10 minutes, the reaction solution was collected after 20 minutes. The mass of reaction solution I consumed was 333.6 g, and the total mass of reaction solutions II and III consumed was 263 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 365.3 g, of which the ethyl 6-chloro-6-oxohexanoate content was 97.5%, and the yield was 96.7%. 36.9 g of unreacted thionyl chloride was recovered, with a content of 98.2%. 119.8 g of sulfur dioxide was recovered, with a content of 98.9%, and a recovery rate of 96.7%. The hydrogen chloride content in the sulfur dioxide was 0.09%. The recovered hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a content of approximately 5.5%, of which the sulfur dioxide content was 0.2‰, and this solution was used for subsequent reactions.

[0032] Example 2

[0033] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this embodiment includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor comprises two sequentially connected reaction sections of equal length (reaction section I and reaction section II). The first reaction section (reaction section I) has a raw material inlet. A hydrogen chloride gas-liquid separator I is located between reaction section I and reaction section II. A hydrogen chloride gas-liquid separator II is located between reaction section II and the back pressure valve. A thionyl chloride inlet is located after hydrogen chloride gas-liquid separator I. The pipeline reactor is constructed of tetrafluoroethylene pipe with a diameter φ of 12 mm and a total length of 900 mm. The liquid outlet of the sulfur dioxide gas-liquid separator is connected to a vacuum distillation unit, and the gas outlet is connected to a condenser. An acid-binding agent inlet is located between the sulfur dioxide gas-liquid separator and the vacuum distillation unit.

[0034] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided in this embodiment includes the following steps:

[0035] Reaction solution I (a solution containing monoethyl adipate prepared by mixing monoethyl adipate and N,N-dimethylformamide (DMF) at a mass ratio of 1:1‰) and reaction solution II (thionyl chloride) were continuously introduced into the first reaction section of the tubular reactor at flow rates of 25 mL / min and 5.7 mL / min, respectively. Reaction solution III (thionyl chloride) was continuously introduced into the remaining reaction sections of the tubular reactor at a flow rate of 5.7 mL / min from the thionyl chloride inlet to continue the reaction. The reaction temperature was set at 50℃, and the pressure in the tubular reactor was controlled at approximately 0.7 MPa by adjusting the back pressure valve to prevent the reaction solution from becoming too hot or too cold. The hydrogen chloride gas can overflow through the hydrogen chloride gas-liquid separator. The hydrogen chloride gas produced by the chlorination reaction is continuously separated and removed from the reaction system. After the chlorination reaction products flow through the back pressure valve, the system pressure becomes atmospheric pressure. Due to the pressure change, the sulfur dioxide in the reaction system changes from liquid to gas. When the material enters the sulfur dioxide gas-liquid separator, the sulfur dioxide gas in the material is separated from the ethyl 6-chloro-6-oxohexanoate liquid. The sulfur dioxide gas is condensed into liquid in the condenser and thus separated out of the system. The condensation temperature in the condenser is -20℃, while the ethyl 6-chloro-6-oxohexanoate liquid continues to the next step of the operation. The acid-binding agent (triethylamine) is added from the acid-binding agent inlet at a flow rate of 0.12 mL / min. The liquid containing ethyl 6-chloro-6-oxohexanoate originating from the sulfur dioxide gas-liquid separator then enters a vacuum distillation apparatus and is distilled under vacuum at a vacuum degree of 2 mmHg. The fraction collected at a temperature of 85–90 °C is the pure ethyl 6-chloro-6-oxohexanoate.

[0036] After equilibration for 10 minutes, the reaction solution was collected after 20 minutes. The mass of reaction solution I consumed was 498.9 g, and the total mass of reaction solutions II and III consumed was 372.5 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 546.6 g, of which the ethyl 6-chloro-6-oxohexanoate content was 96.7%, and the yield was 95.7%. 45.1 g of unreacted thionyl chloride was recovered, with a content of 98.3%. 172.1 g of sulfur dioxide was recovered, with a content of 98.1%, and a recovery rate of 95.8%. The hydrogen chloride content in the sulfur dioxide was 0.08%. The recovered hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a content of 9%, of which the sulfur dioxide content was 0.15‰, which was used for subsequent reactions.

[0037] Example 3

[0038] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this embodiment includes, along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor includes five reaction sections of equal length connected in sequence (i.e., reaction section I, reaction section II, reaction section III, reaction section IV, and reaction section V). The first reaction section (reaction section I) is equipped with a raw material inlet. A hydrogen chloride gas-liquid separator I is installed between reaction section I and reaction section II. A hydrogen chloride gas-liquid separator II is installed between reaction section II and reaction section III. A hydrogen chloride gas-liquid separator III is installed between reaction section III and reaction section IV. A hydrogen chloride gas-liquid separator IV is installed between reaction section IV and reaction section V. A hydrogen chloride gas-liquid separator V is installed between reaction section V and the back pressure valve. A thionyl chloride inlet is installed after hydrogen chloride gas-liquid separators I, II, III, and IV. The pipeline reactor is constructed using PTFE pipes with a diameter of 20 mm and a total length of 2000 mm. The liquid outlet of the sulfur dioxide gas-liquid separator is connected to the vacuum distillation unit, and the gas outlet is connected to the condenser. An acid-binding agent inlet is provided between the sulfur dioxide gas-liquid separator and the vacuum distillation unit.

[0039] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided in this embodiment includes the following steps:

[0040] Reaction solution I (a solution containing monoethyl adipate prepared by mixing monoethyl adipate and dimethylacetamide at a mass ratio of 1:2‰) and reaction solution II (thionyl chloride) were continuously introduced into the first reaction section of the pipeline reactor at flow rates of 17 mL / min and 1.62 mL / min, respectively. Reaction solution III (thionyl chloride) was continuously introduced into the remaining reaction sections of the pipeline reactor at a flow rate of 1.62 mL / min from the thionyl chloride inlet to continue the reaction. The reaction temperature was set at 20℃, and the pressure in the pipeline reactor was controlled at approximately 0.8 MPa by adjusting the back pressure valve to prevent the reaction solution from flowing out. The hydrogen chloride gas overflows from the hydrogen chloride gas-liquid separator, which continuously separates and removes the hydrogen chloride gas produced by the chlorination reaction from the reaction system. Afterwards, the chlorination reaction products flow through a back pressure valve, where the pressure becomes atmospheric pressure. Due to the pressure change, sulfur dioxide in the reaction system changes from a liquid to a gaseous state. When the material enters the sulfur dioxide gas-liquid separator, the sulfur dioxide gas in the material separates from the ethyl 6-chloro-6-oxohexanoate liquid. The sulfur dioxide gas is condensed into liquid in a condenser, thus separating it from the system. The condensation temperature in the condenser is -10℃, while the ethyl 6-chloro-6-oxohexanoate liquid continues to the next step. An acid-binding agent (pyridine) is added at a flow rate of 0.17 mL / min through the acid-binding agent inlet. The liquid containing ethyl 6-chloro-6-oxohexanoate from the sulfur dioxide gas-liquid separator then enters a vacuum distillation apparatus for vacuum distillation at a vacuum degree of 2 mmHg. The fraction collected at a temperature of 85–90℃ is the purified ethyl 6-chloro-6-oxohexanoate.

[0041] After equilibration for 10 min, the reaction solution from the 20 min reaction was collected. The mass of reaction solution I consumed was 334.2 g, and the total mass of reaction solutions II and III consumed was 265.7 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 367.7 g, of which the ethyl 6-chloro-6-oxohexanoate content was 97.3%, and the yield was 97.0%. 37.9 g of unreacted thionyl chloride was recovered, with a content of 98.3%. 119.5 g of sulfur dioxide was recovered, with a content of 98.8%, and a recovery rate of 96.3%. The hydrogen chloride content in the sulfur dioxide was 0.07%. The recovered hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a concentration of approximately 5.7%, of which the sulfur dioxide content was 0.23‰, which was used for subsequent reactions.

[0042] Example 4

[0043] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this embodiment does not have an acid-binding agent inlet or an acid-binding agent feed pump; the remaining components and connection methods are the same as in Example 1.

[0044] The continuous preparation method of ethyl 6-chloro-6-oxohexanoate provided in this embodiment does not include an acid-binding agent, and the other conditions are the same as in Example 1.

[0045] After equilibration for 10 minutes, the reaction solution was collected after 20 minutes. The mass of reaction solution I consumed was 332.9 g, and the total mass of reaction solutions II and III consumed was 263.7 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 360.2 g, of which the ethyl 6-chloro-6-oxohexanoate content was 96.5%, and the yield was 94.6%. 33.8 g of unreacted thionyl chloride was recovered, with a content of 95.4%. 119.5 g of sulfur dioxide was recovered, with a content of 98.4%, and a recovery rate of 96.1%. The hydrogen chloride content in the sulfur dioxide was 0.07%. The recovered hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a content of approximately 5.2%, of which the sulfur dioxide content was 0.16‰, which was used for subsequent reactions.

[0046] Comparative Example 1

[0047] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this comparative example does not include hydrogen chloride gas-liquid separator I, hydrogen chloride gas-liquid separator II, and hydrogen chloride gas-liquid separator III; the remaining components and connection methods are the same as in Example 1.

[0048] After equilibration for 10 minutes, the reaction solution from the 20-minute reaction was collected. The mass of reaction solution I consumed was 331.9 g, and the total mass of reaction solutions II and III consumed was 263 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 310.2 g, of which the ethyl 6-chloro-6-oxohexanoate content was 97.6%, with a yield of 82.6%. 40.7 g of unreacted thionyl chloride was recovered, with a content of 95.3%. 90 g of sulfur dioxide was recovered, with a content of 84.9%, a recovery rate of 73.5%, and the hydrogen chloride content in the sulfur dioxide was 3%. The recovered hydrogen chloride gas (both sulfur dioxide and hydrogen chloride gas generated during the reaction are ultimately separated by a sulfur dioxide gas-liquid separator because sulfur dioxide and hydrogen chloride have significantly different boiling points; at -15°C, sulfur dioxide condenses into a liquid, while hydrogen chloride continues to exist as a gas, thus achieving the separation of sulfur dioxide and hydrogen chloride gas) is passed into 1L of water to prepare a dilute hydrochloric acid solution with a content of approximately 4.7%, of which the sulfur dioxide content is approximately 1‰, and is used for subsequent reactions.

[0049] Comparative Example 2

[0050] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this comparative example does not include a back pressure valve or a sulfur dioxide gas-liquid separator; the remaining components and connections are the same as in Example 1. Accordingly, in the continuous preparation method of ethyl 6-chloro-6-oxohexanoate, the chlorination reaction pressure is atmospheric pressure, and all the gases generated during the reaction are introduced into a transfer tank and condensed to -15°C. At this temperature, sulfur dioxide is liquefied and hydrogen chloride is gaseous, thus achieving the separation and recovery of sulfur dioxide and hydrogen chloride.

[0051] After equilibration for 10 min, the reaction solution was collected after 20 min. The mass of reaction solution I consumed was 332.3 g, and the total mass of reaction solutions II and III consumed was 262.5 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate was 345.2 g, of which the content of ethyl 6-chloro-6-oxohexanoate monoethyl ester hexanoyl chloride was 95.2%, and the yield was 94.5%. 40.7 g of unreacted thionyl chloride was recovered, with a content of 95.3%. 90 g of sulfur dioxide was recovered, with a content of 90.8%, and a recovery rate of 78.5%. The hydrogen chloride content in the sulfur dioxide was approximately 3%. Hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a content of approximately 5%, of which the sulfur dioxide content was 8‰, which was used for subsequent reactions.

[0052] Comparative Example 3

[0053] The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate used in this comparative example does not have a thionyl chloride inlet or a thionyl chloride feed pump; the remaining components and connections are the same as in Example 1. Accordingly, in the continuous preparation method of ethyl 6-chloro-6-oxohexanoate, all thionyl chloride raw materials are introduced from the first reaction stage.

[0054] After equilibration for 10 min, the reaction solution from 20 min was collected. The mass of reaction solution I consumed was 331.8 g, and the total mass of reaction solutions II and III consumed was 252.8 g. The mass of the refined ethyl 6-chloro-6-oxohexanoate obtained was 352.8 g, of which the content of ethyl 6-chloro-6-oxohexanoate monoethyl ester hexanoyl chloride was 94.0%, with a yield of 90.6%. 26.7 g of unreacted thionyl chloride was recovered, with a content of 96.1%. 90 g of sulfur dioxide was recovered, with a content of 91.2%, a recovery rate of 72.4%, and the hydrogen chloride content in the sulfur dioxide was approximately 2.7%. Hydrogen chloride gas was passed into 1 L of water to prepare a dilute hydrochloric acid solution with a content of approximately 5.6%, of which the sulfur dioxide content was 1‰, which was used for subsequent reactions.

[0055] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention without departing from the principles and spirit of the present invention.

Claims

1. A continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate, characterized in that, The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate includes, in sequence along the material flow direction, a pipeline reactor, a back pressure valve, and a sulfur dioxide gas-liquid separator. The pipeline reactor includes at least two reaction sections connected in sequence. The first reaction section is provided with a raw material inlet. After each reaction section, a hydrogen chloride gas-liquid separator is provided, and after the hydrogen chloride gas-liquid separator located between two adjacent reaction sections, a thionyl chloride inlet is provided.

2. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate according to claim 1, characterized in that, The pipeline reactor is a tetrafluoroethylene pipeline with a diameter φ of 3~50mm and a total length of 100~2000mm.

3. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate according to claim 1, characterized in that, The number of reaction sections is 2 to 5.

4. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate according to claim 1, characterized in that, The different reaction sections of the pipeline reactor have the same length.

5. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate according to claim 1, characterized in that, The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate further includes a vacuum distillation apparatus and a condenser. The vacuum distillation apparatus is connected to the liquid outlet of a sulfur dioxide gas-liquid separator, and the condenser is connected to the gas outlet of the sulfur dioxide gas-liquid separator.

6. The continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate according to claim 5, characterized in that, An acid-binding agent inlet is also provided between the sulfur dioxide gas-liquid separator and the vacuum distillation unit.

7. A continuous preparation method for ethyl 6-chloro-6-oxohexanoate, characterized in that, The method is carried out in the continuous preparation apparatus for ethyl 6-chloro-6-oxohexanoate as described in claim 1. The method includes continuously feeding reaction solution I and reaction solution II into the first reaction section of the pipeline reactor from the raw material inlet for chlorination reaction, and continuously feeding reaction solution III into the remaining reaction sections of the pipeline reactor from the thionyl chloride inlet for chlorination reaction. The reaction solution I is a solution containing monoethyl adipate and an amide catalyst, and both reaction solutions II and III are thionyl chloride. During the chlorination reaction, the pressure in the pipeline reactor is controlled by a back pressure valve so that the sulfur dioxide produced by the chlorination reaction is in a liquid state and the hydrogen chloride is in a gaseous state. At the same time, the hydrogen chloride gas produced by the chlorination reaction is separated and removed from the reaction system by a hydrogen chloride gas-liquid separator. After the reaction is completed, the reaction solution is depressurized through the back pressure valve, and the sulfur dioxide changes from a liquid state to a gaseous state. Then, the sulfur dioxide is separated by a sulfur dioxide gas-liquid separator to obtain crude ethyl 6-chloro-6-oxohexanoate.

8. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The mass ratio of monoethyl adipic acid to amide catalyst in reaction solution I is 1:(1‰~4‰).

9. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The amide catalyst is selected from at least one of N,N-dimethylformamide and dimethylacetamide.

10. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The flow rate of reaction solution I is 1~30 mL / min.

11. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The flow rate of reaction solution II is 0.5~10 mL / min.

12. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The flow rate of reaction solution III is the same as that of reaction solution II.

13. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The chlorination reaction is carried out at a temperature of 20~50℃ and a pressure of 0.5~1.2MPa.

14. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 7, characterized in that, The method further includes adding an acid-binding agent to crude ethyl 6-chloro-6-oxohexanoate, followed by vacuum distillation to obtain refined ethyl 6-chloro-6-oxohexanoate; and / or, the method further includes condensing and recovering gaseous sulfur dioxide.

15. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 14, characterized in that, The condensation temperature is -20 to -10℃.

16. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 14, characterized in that, The acid-binding agent is selected from at least one of pyridine, 2-methylpyridine and triethylamine.

17. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 14, characterized in that, The amount of the acid-binding agent is 0.2-1% of the mass of monoethyl adipic acid fed into the feed.

18. The continuous preparation method of ethyl 6-chloro-6-oxohexanoate according to claim 14, characterized in that, The fraction obtained by vacuum distillation at a vacuum degree of 2 mmHg and a temperature of 85~90℃ is the refined ethyl 6-chloro-6-oxohexanoate.

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