CN118084664A - Method for producing 6, 8-dichloro ethyl octanoate - Google Patents

Abstract

The invention provides a production method of 6, 8-dichloro ethyl octanoate. The production method comprises the following steps: continuously introducing adipic acid, ethanol, diethyl adipate, a first catalyst and a water-carrying agent into a first continuous reactor for esterification reaction to obtain monoethyl adipate; continuously introducing the monoethyl adipate, the first chlorinating agent and the second catalyst into a second continuous reactor for carrying out first chlorination reaction to obtain a second product system, and continuously mixing the second product system with a third solvent and a third catalyst to obtain a continuous complexing system; introducing the catalyst and ethylene gas into a continuous gas-liquid reactor for continuous addition reaction to obtain an 8-chloro-6-oxo-ethyl octanoate solution; introducing the product, the phase transfer catalyst and the reducing agent solution into a fourth continuous reactor for continuous reduction reaction to obtain a reduction product; and (3) introducing the reduction product, a second chlorinating agent, a fifth solvent and a fifth catalyst into a fifth continuous reactor for a second chlorination reaction, and treating to obtain a target product.

Description

Method for producing 6, 8-dichloro ethyl octanoate

Technical Field

The invention relates to the technical field of synthesis of medical intermediates, in particular to a production method of 6, 8-dichloro ethyl octanoate.

Background

Lipoic acid belongs to a class of compounds in the vitamin B group, has strong antioxidant capacity, is the only standard medicine capable of meeting antioxidant evaluation at present, and is called as a universal antioxidant. Lipoic acid is widely used in foreign countries mainly as a medicine, and also as a dietary supplement and a cosmetic raw material. The medicine is mainly applied in the field of medicine in China, and is mainly used for treating various diseases such as diabetic peripheral neuropathy, heart disease, alzheimer disease and the like.

Ethyl 6, 8-dichloro octanoate is an important organic intermediate for the synthesis of lipoic acid. The current method for synthesizing the 6, 8-dichloro ethyl octanoate mainly comprises an adipic acid route, a cyclohexanone route and the like. The method for preparing cyclohexanone and its derivatives has the disadvantages of low price of initial raw materials, low total reaction yield and the like, although the method has few reaction steps and simple operation. The adipic acid method is a mature and industrialized process route in the prior art, and the method takes adipic acid as a starting material to prepare the lipoic acid key intermediate 6, 8-dichloro ethyl octanoate through five-step reactions such as single esterification, acyl chlorination, addition, reduction, chlorination and the like.

The intermittent reaction kettle is used for industrial production of adipic acid, the reaction heat release amount is large, raw materials are slowly dripped in actual production, the time consumption is long, if the dripping speed is not well controlled, more impurities are generated, the system in the reaction kettle is often insufficiently mixed, the reaction rate is slow, the conversion rate is not high, the extraction efficiency is low in post-treatment, the water phase loss is more, the purity and the yield of the products produced in batches are low, and the quality of the products among batches is unstable.

Patent application CN116496159a provides a process for preparing ethyl 6, 8-dichloro-octanoate, which comprises (1) reacting a compound of formula ii with thionyl chloride to obtain a compound of formula iii; (2) Introducing ethylene gas into a compound of the formula III in the presence of aluminum trichloride, dropwise adding stoichiometric water after the reaction is finished, separating out the aluminum trichloride in the form of aluminum trichloride hexahydrate, and centrifugally separating to obtain a solution containing the compound of the formula IV; (3) Reacting a compound of formula IV with a reducing agent in the presence of a base to obtain a compound of formula V; (4) And (3) heating the compound of the formula V and thionyl chloride in the presence of a catalyst to react to obtain the 6, 8-ethyl dichloro octoate. When the compound of the formula IV is prepared, the stoichiometric water quenching reaction is added to enable aluminum trichloride to react into hexahydrate aluminum trichloride to be directly separated out from the reaction, and the next reaction can be carried out only by simple filtration or centrifugation.

The patent with publication No. CN105693510A provides a preparation method of 6, 8-dichloro ethyl octanoate, which takes N, N-dimethylbenzylamine as an acid binding agent, firstly reacts 6-hydroxy-8-chloro ethyl octanoate with a chlorinating agent in an organic solvent, and controls the reaction temperature, heat preservation is carried out after the reaction is finished, the heat preservation temperature is controlled, the heat preservation time is controlled, the reaction liquid is obtained, water is added into the reaction liquid, the upper layer is an organic phase, the decompression rectification is carried out, the 6, 8-dichloro ethyl octanoate is obtained, the lower layer is added with alkali to adjust the pH for layering, the upper layer is dehydrated by anhydrous sodium sulphate, and the N, N-dimethylbenzylamine is obtained for recycling.

The traditional process is to use a batch reactor for production, and the single batch treatment volume is large, but the traditional process has the following defects: 1. the reaction releases heat and discharges air severely, the dropping speed is slow, the production efficiency is low, and the productivity is limited; 2. the temperature gradient is large, and impurities are easy to generate due to local overheating; 3. the gas is unevenly distributed, and the reaction time is long; 4. the batch reaction kettle has large liquid holdup and low safety coefficient; 5. the extraction efficiency of the reaction kettle is low, the water phase loss is high, and the solvent consumption is high; 6. the post-treatment process is complicated, and the single batch production period is long; 7. the quality of products is different among batches, and the quality of the products is unstable; 8. the batch reaction kettle has low process automation degree and high labor cost.

How to simplify the production process of the ethyl 6, 8-dichloro octoate and reduce the production cost is still a problem to be solved by the technicians in the field.

Disclosure of Invention

The invention mainly aims to provide a production method of 6, 8-dichloro ethyl octanoate, which aims to solve the problems that the 6, 8-dichloro ethyl octanoate in the prior art depends on an intermittent method for production, and has complex process and higher cost.

In order to achieve the above object, according to one aspect of the present invention, there is provided a method for producing ethyl 6, 8-dichlorooctanoate, the method comprising: continuously introducing adipic acid, ethanol, diethyl adipate, a first catalyst and a water-carrying agent into a first continuous reactor for esterification reaction, continuously introducing a reaction system obtained by the esterification reaction into a low-temperature device, terminating the reaction to obtain a first product system, performing solid-liquid separation on the first product system to obtain solid adipic acid and filtrate, and performing first continuous purification treatment on the filtrate to obtain monoethyl adipate; continuously introducing the monoethyl adipate, the first chlorinating agent and the second catalyst into a second continuous reactor for carrying out first chlorination reaction to obtain a second product system, and continuously mixing the second product system, a third solvent and the third catalyst to obtain a continuous complexing system; introducing the continuous complexing system and ethylene gas into a continuous gas-liquid reactor for continuous addition reaction to obtain a third product system, and carrying out third continuous purification treatment on the third product system to obtain an 8-chloro-6-oxo-ethyl octanoate solution; introducing an ethyl 8-chloro-6-oxooctoate solution, a phase transfer catalyst and a reducing agent solution into a fourth continuous reactor for continuous reduction reaction, continuously quenching a product obtained by the continuous reduction reaction to obtain a fourth product system, and performing fourth continuous purification treatment on the fourth product system to obtain a reduced product of 6-hydroxy-8-chlorooctoate; and (3) introducing the reduction product of 6-hydroxy-8-chloroethyl octanoate, a second chlorinating agent, a fifth solvent and a fifth catalyst into a fifth continuous reactor for a second chlorination reaction to obtain a second chlorination reaction product, and carrying out fifth continuous purification treatment on the second chlorination reaction product to obtain the target product of 6, 8-dichloroethyl octanoate.

Further, the first continuous reactor is any one of a column reactor and a tubular reactor, preferably, adipic acid is solid adipic acid, the first continuous reactor is a column reactor, the solid adipic acid is continuously fed from the top of the column reactor, and ethanol, diethyl oxalate, a first catalyst and a water-carrying agent are continuously fed from the bottom of the column reactor;

Preferably, the reaction system obtained by the esterification overflows from the upper part of the first continuous reactor to a low-temperature device, and a low-temperature first organic solvent is continuously added in the low-temperature device, preferably, the first organic solvent comprises any one or more of toluene and methylene dichloride;

preferably, the temperature of the low temperature device is-10 to 30 ℃, more preferably 0 to 15 ℃,

Preferably, the first continuous purification treatment comprises: and (3) alkali washing, acid washing and concentrating to obtain a concentrated solution of the monoethyl adipate.

Further, the temperature of the esterification reaction is 50-150 ℃; preferably 75-85 ℃;

preferably, the reaction time of the esterification reaction is 0.5-4 hours, more preferably 1-3 hours;

Preferably, the feeding speed of adipic acid is 1.2-2.0 mol/h, the feeding speed of diethyl adipate is 0.5-2.0 mol/h, the feeding speed of ethanol is 1-5 mol/h, the feeding speed of the first catalyst is 0.01-0.5 mol/h, and the feeding speed of the water-carrying agent is 0.5-5 g/g.

Further, the reaction temperature of the first chlorination reaction is 0-70 ℃, the reaction time is 0.5-4 h, the reaction pressure is 0.2-2 MPa, and preferably, the second continuous reactor is a tubular reactor;

preferably, the first chlorinating agent comprises any one or more of thionyl chloride, oxalyl chloride and triphosgene; preferably, the molar ratio of the first chlorinating agent to the monoethyl adipate is 1.0-1.5: 1, a step of;

preferably, the second catalyst comprises one or more of DMF and pyridine, and preferably, the molar ratio of the second catalyst to the monoethyl adipate is 0.01-0.5:1.

Further, the second product system, the third solvent and the third catalyst are mixed in a continuous tank reactor, preferably, the third solvent comprises any one or more of dichloroethane and dichloromethane; the third catalyst comprises any one or more of aluminum chloride, ferric chloride and boron trifluoride;

the molar ratio of the third catalyst to the ethyl 6-chloro-6-oxohexanoate in the second product system is 1.5-4:1.

Further, introducing the continuous complexing product system and ethylene gas into the bottom of a continuous gas-liquid reactor, wherein a gas distributor is arranged at the bottom of the gas-liquid reactor;

Preferably, the molar ratio of the ethylene gas to the ethyl 6-chloro-6-oxohexanoate in the second product system is 0.5-4:1;

Preferably, the third product system overflows from the upper part of the continuous gas-liquid reactor to a low-temperature quenching device to obtain a third quenched product system, and the third quenched product system is subjected to third continuous purification treatment;

preferably, the third continuous purification treatment comprises continuous alkaline washing and washing liquid separation by adopting a continuous extraction module to obtain the 8-chloro-6-oxo-octanoic acid ethyl ester solution.

Further, the temperature of the continuous addition reaction is-10-30 ℃ and the time is 5-40 min.

Further, the reducing agent comprises any one or more of potassium borohydride and sodium borohydride; the phase transfer catalyst comprises any one or more of tetrabutylammonium bromide and tetrabutylammonium chloride;

Preferably, the molar ratio of the reducing agent to the 8-chloro-6-oxoethyl octanoate in the 8-chloro-6-oxoethyl octanoate solution is 0.25-2.0:1, the molar ratio of the phase transfer catalyst to the 8-chloro-6-oxoethyl octanoate in the 8-chloro-6-oxoethyl octanoate solution is 0.01-0.2:1, and the reducing agent solution comprises ammonia water with the concentration of 5-25 wt%;

the continuous quenching treatment comprises the steps of continuously introducing a product obtained by the continuous reduction reaction into a kettle-type reactor to be mixed with a continuously introduced acid solution, wherein the acid solution is preferably 5-37% hydrochloric acid;

and the fourth continuous purification treatment comprises liquid separation, water washing and concentration to obtain the 6-hydroxy-8-chlorooctanoic acid ethyl ester.

Further, the reaction temperature of the continuous reduction reaction is 0-70 ℃; preferably 35-45 ℃,

The reaction time of the continuous reduction reaction is 0.5 to 4 hours, more preferably 0.5 to 1.5 hours.

Further, the fifth continuous reactor is a continuous column reactor; preferably, the reaction temperature of the second chlorination reaction is 40-110 ℃; preferably 45-55 ℃; preferably, the reaction time of the second chlorination reaction is 0.5-4 hours; preferably 0.5 to 1.5 hours.

By applying the technical scheme of the application, the preparation of the 6, 8-dichloro ethyl octanoate by the full-continuous production process is realized, the problems of long operation period, low equipment utilization rate, different product quality, low automation degree and the like in the conventional intermittent production are well solved, the uniformity of the product is ensured, the automation degree is high, and the labor cost is saved. Further, the continuous device adopted by the application has large specific surface area, is favorable for heat transfer, can reduce the temperature difference of the system, and can well solve the problem of yield reduction caused by more impurities generated by large temperature difference in the reaction process; on the other hand, the continuous device has small liquid holdup and high controllability, and remarkably improves the conversion rate of raw materials.

Drawings

The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this specification, illustrate embodiments of the application and together with the description serve to explain the application. In the drawings:

figure 1 shows a schematic diagram of a process flow for the full continuous synthesis of monoethyl adipate according to example 1 of the present invention.

Wherein the above figures include the following reference numerals: 101. a solid adipic acid storage device; 102. a column reactor; 103. a first storage tank; 104. a second storage tank; 105. a third tank; 106. a precooling module; 107. a condenser; 108. a first continuous reaction kettle; 109. a solid-liquid separation device; 110. a fourth tank; 111. a first continuous extraction module; 112. a second continuous extraction die; 113. a third continuous extraction module; 114. and a fourth continuous extraction module.

Detailed Description

It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other. The application will be described in detail below with reference to the drawings in connection with embodiments.

As analyzed by the background technology of the application, the prior art has the problems of complex process and higher cost of the 6, 8-dichloro ethyl octanoate produced by a batch method, and the application provides a production method of the 6, 8-dichloro ethyl octanoate.

The production method of the ethyl 6, 8-dichloro octoate comprises the following steps: continuously introducing adipic acid, ethanol, diethyl adipate, a first catalyst and a water-carrying agent into a first continuous reactor for esterification reaction, continuously introducing a reaction system obtained by the esterification reaction into a low-temperature device, terminating the reaction to obtain a first product system, performing solid-liquid separation on the first product system to obtain solid adipic acid and filtrate, and performing first continuous purification treatment on the filtrate to obtain monoethyl adipate; continuously introducing the monoethyl adipate, the first chlorinating agent and the second catalyst into a second continuous reactor for carrying out first chlorination reaction to obtain a second product system, and continuously mixing the second product system, a third solvent and the third catalyst to obtain a continuous complexing system; introducing the continuous complexing system and ethylene gas into a continuous gas-liquid reactor for continuous addition reaction to obtain a third product system, and carrying out third continuous purification treatment on the third product system to obtain an 8-chloro-6-oxo-ethyl octanoate solution; introducing an ethyl 8-chloro-6-oxooctoate solution, a phase transfer catalyst and a reducing agent solution into a fourth continuous reactor for continuous reduction reaction, continuously quenching a product obtained by the continuous reduction reaction to obtain a fourth product system, and performing fourth continuous purification treatment on the fourth product system to obtain a reduced product of 6-hydroxy-8-chlorooctoate; and (3) introducing the reduction product of 6-hydroxy-8-chloroethyl octanoate, a second chlorinating agent, a fifth solvent and a fifth catalyst into a fifth continuous reactor for a second chlorination reaction to obtain a second chlorination reaction product, and carrying out fifth purification treatment on the second chlorination reaction product to obtain the target product of 6, 8-dichloro ethyl octanoate.

The application realizes the preparation of the 6, 8-dichloro ethyl octanoate by the fully continuous production process in the mode, well solves the problems of long operation period, low equipment utilization rate, different product quality, low automation degree and the like in the conventional intermittent production, ensures the uniformity of the product, has high automation degree and saves labor cost. Further, the continuous device adopted by the application has large specific surface area, is favorable for heat transfer, can reduce the temperature difference of the system, and can well solve the problem of yield reduction caused by more impurities generated by large temperature difference in the reaction process; on the other hand, the continuous device has small liquid holdup and high controllability, and remarkably improves the conversion rate of raw materials.

The synthetic route of the 6, 8-dichloro ethyl octanoate adopted by the application is as follows:

In the process of synthesizing the monoethyl adipate by taking adipic acid as a raw material, in order to improve the yield of a target product monoethyl adipate, diethyl adipate is added into a starting raw material to promote the reaction to proceed towards the direction of generating the monoethyl adipate, and researchers of the application find that the yield of the monoethyl adipate can be obviously improved by adding diethyl adipate into the raw material in the continuous production process of the application.

In some preferred embodiments of the present application, the first continuous reactor is any one of a column reactor and a tubular reactor.

In some typical embodiments of the application, the adipic acid added into the reactor is solid adipic acid, the first continuous reactor is a column reactor, the solid adipic acid is continuously fed from the top of the first continuous reactor, and the ethanol, diethyl oxalate, the first catalyst and the water-carrying agent are continuously fed from the bottom of the column reactor, so that the process is further simplified, the conversion rate of raw adipic acid can be improved, and the yield of the target product diethyl oxalate can be improved. In some embodiments of the application, a condenser is provided at the top of the first continuous reactor to effect the split reflux.

The first catalyst and the water-carrying agent can be selected in the prior art, for example, the first catalyst is one or more of p-toluenesulfonic acid, sulfuric acid and hydrochloric acid, and the water-carrying agent is one or more of toluene and 1, 2-dichloroethane.

In some embodiments of the application, the temperature of the esterification reaction is 50-150 ℃, preferably 75-85 ℃; the reaction time is 0.5-4 h, more preferably 1-3 h, the conversion rate of adipic acid is high, and the byproducts are fewer.

In some preferred embodiments of the application, the feed rate of adipic acid is 1.2-2.0 mol/h, the feed rate of diethyl adipate is 0.5-2.0 mol/h, the feed rate of ethanol is 1-5 mol/h, the feed rate of p-toluenesulfonic acid is 0.01-0.5 mol/h, and the feed rate of water-carrying agent is 0.5-5 g/g, wherein "g/g" represents the corresponding grams of water-carrying agent per gram of adipic acid raw material.

Further, the reaction system obtained by the esterification reaction overflows from the upper part of the first continuous reactor to a low-temperature device, and the low-temperature first organic solvent is continuously supplemented in the low-temperature device to realize low-temperature stopping of the reaction, and the low-temperature solvent is supplemented to avoid the problem that the system is not easy to flow due to solidification of a cooling system, so that the fluidity of the system is increased, and continuous production is realized. Preferably, the temperature of the low temperature device is-10 to 30 ℃, more preferably 0 to 15 ℃, and the first organic solvent with the temperature range is preferably added. The first organic solvent is preferably any one or more of toluene and methylene chloride.

And (3) carrying out continuous solid-liquid separation on the first product system after the low temperature suspension to obtain solid adipic acid and filtrate, drying the obtained solid adipic acid, recycling the obtained solid adipic acid, and carrying out first continuous purification treatment on the filtrate. Preferably, the first continuous purification treatment comprises: and (3) alkali washing, acid washing and concentrating to obtain a concentrated solution of the monoethyl adipate.

In some exemplary embodiments of the application, the production process of the application continuously produces monoethyl adipate as follows: pumping diethyl adipate, ethanol, a first catalyst and a water-carrying agent into the bottom of the column reactor in proportion through a material beating module; continuously feeding solid adipic acid from the top of the column reactor through a feeding module, and arranging a condenser at the top for water diversion reflux; the reaction system in the column reactor overflows from the upper part to a continuous reaction kettle for low-temperature termination, and meanwhile, a material beating module and a precooling module are utilized for supplementing low-temperature toluene; carrying out solid-liquid separation on the terminated system, drying the solid adipic acid, then recovering the solid adipic acid, and collecting filtrate; pumping the filtrate and saturated sodium carbonate solution into a continuous extraction module through a beating module in proportion for alkali washing and separating liquid, wherein the upper layer is marked as an organic phase 1, and the lower layer is marked as a water phase 1; the water phase 1 and toluene enter a continuous extraction module to be washed and separated, the upper layer is marked as an organic phase 2, and the lower layer is marked as a water phase 2; the organic phases 1 and 2 enter a continuous concentration module, toluene is cooled by a condenser and then is used mechanically, and concentrated solution diethyl adipate is recovered; hydrochloric acid and toluene enter a continuous extraction module through a continuous mixing module to be pickled with the water phase 2, wherein the upper layer is marked as an organic phase 3, and the lower layer is marked as the water phase 3; the water phase 3 and toluene enter a continuous extraction module to be washed and separated, the upper layer is marked as an organic phase 4, toluene and monoethyl adipate, and the lower layer is marked as a water phase 4 (wastewater phase); the organic phases 3 and 4 enter a continuous concentration module, toluene is cooled by a condenser and then is used mechanically, and concentrated solution, namely concentrated solution of monoethyl adipate, is collected. The preparation process adopts a continuous extraction mode, increases the contact area, can greatly reduce the solvent consumption, reduces the product loss and the extraction times, and has better multistage extraction effect.

Continuously introducing the adipic acid monoethyl ester, the first chlorinating agent and the second catalyst into a second continuous reactor to carry out a first chlorination reaction to prepare the 6-chloro-6-oxo-ethyl caproate. In some exemplary embodiments of the application, the second continuous reactor is a tubular reactor.

The first chlorinating agent and the second catalyst in the first chlorination reaction may be selected in the art. Preferably, the first chlorinating agent comprises any one or more of thionyl chloride, oxalyl chloride and triphosgene; preferably, the molar ratio of the first chlorinating agent to the monoethyl adipate is 1.0-1.5: 1. preferably, the second catalyst comprises one or more of DMF and piperidine, and preferably, the molar ratio of the second catalyst to the monoethyl adipate is 0.01-0.5:1. By adopting the method of the application, the first chlorination reaction does not need to add extra solvent, and the second product system after the reaction can be directly used for the next continuous addition reaction.

In some embodiments of the application, the reaction temperature of the first chlorination reaction is 0-70 ℃, the reaction time is 0.5-4 h, the reaction pressure is 0.2-2 MPa, preferably, the reaction temperature is 35-45 ℃, the reaction time is 0.5-1.5 h, and the reaction pressure is 1-1.5 MPa, which is beneficial to further improving the yield of the 6-chloro-6-oxo ethyl caproate in the second product system and reducing the energy consumption.

In some preferred embodiments of the present application, the second product system, the third solvent and the third catalyst are mixed in a continuous kettle reactor, the 6-chloro-6-oxohexanoate ethyl ester and the third catalyst form a complex, preferably, the mixing temperature is 0-5 ℃, preferably, the third solvent comprises any one or more of dichloroethane and dichloromethane; the third catalyst is Lewis acid, which is not particularly required in the present application and may be selected in the prior art, and includes, by way of example, any one or more of aluminum chloride, ferric chloride, boron trifluoride.

In some embodiments of the present application, for further addition reaction yields, the molar ratio of the third catalyst to the ethyl 6-chloro-6-oxooctanoate in the second product system is 1.5-4:1. Preferably, the third continuous reactor is a continuous kettle reactor, and the third catalyst is continuously fed from the top of the third reactor, so that the mixing effect is improved.

In some exemplary embodiments of the application, the continuous complexation product system and ethylene gas are passed to the bottom of a continuous gas-liquid reactor, the bottom of the gas-liquid reactor being provided with a gas distributor; through the arrangement of the gas distributor, the gas and the liquid can be fully mixed, the reaction time and the material equivalent are reduced, and the raw material conversion rate is improved. Preferably, the molar ratio of the ethylene gas to the ethyl 6-chloro-6-oxohexanoate in the second product system is 0.5-4:1.

In some preferred embodiments of the present application, the temperature of the continuous addition reaction is-10 to 30 ℃, the time is 5 to 40min, preferably, the temperature of the reaction is 5 to 15 ℃, and the time of the reaction is 5 to 15min.

In some preferred embodiments of the present application, the third product system overflows from the upper portion of the continuous gas-liquid reactor to a low temperature quenching device to obtain a third quenched product system, and the third quenched product system is subjected to a third continuous purification treatment; preferably, the temperature of the low-temperature quenching device is 0-40 ℃, more preferably 0-15 ℃, and low-temperature water can be supplemented by the material beating module and the precooling module at the same time.

Preferably, the third continuous purification treatment comprises continuous alkaline washing and washing liquid separation by adopting a continuous extraction module to obtain the 8-chloro-6-oxo-octanoic acid ethyl ester solution.

In some exemplary embodiments of the present application, monoethyl adipate continuously prepared by the above process was prepared by a first chlorination, continuous addition reaction to prepare an ethyl 8-chloro-6-oxooctanoate solution by the following process: pumping the adipic acid monoethyl ester, the first chlorinating agent and the second catalyst into a tubular second continuous reactor through a material beating module; the reaction liquid prepared from the second continuous reactor and the third solvent enter a continuous reaction kettle through a precooling module for complexation, and the third catalyst is continuously fed from the top of the reaction kettle through a feeding module to continuously prepare a complexation system; pumping the obtained complexing system and ethylene gas into the bottom of a gas-liquid reactor in proportion through a material beating module, wherein a gas distributor is arranged at the bottom of the gas-liquid reactor; the reaction system in the gas-liquid reactor overflows from the upper part to a continuous reaction kettle for low-temperature quenching, and low-temperature water is supplemented by a material beating module and a precooling module; the quenching system enters a liquid separation module to carry out continuous liquid separation, the left light phase is marked as a water phase 5 (waste water phase), and the right heavy phase is marked as an organic phase 5; pumping the organic phase 5 and saturated sodium bicarbonate solution into a continuous extraction module through a material beating module and a precooling module in proportion, performing alkaline washing and liquid separation, wherein the upper layer is marked as a water phase 6 (wastewater phase), and the lower layer is marked as the organic phase 6; the organic phase 6 and water enter a continuous extraction module for washing and separating liquid, the upper layer is marked as an aqueous phase 7 (waste water phase), and the lower layer is marked as an organic phase 7 (namely 8-chloro-6-oxo-ethyl octanoate solution).

The reducing agent and phase transfer catalyst in the continuous reduction reaction may be selected in the art, and in some embodiments of the application, the reducing agent comprises any one or more of potassium borohydride, sodium borohydride; the phase transfer catalyst comprises any one or more of tetrabutylammonium bromide and tetrabutylammonium chloride; preferably, the molar ratio of the reducing agent to the 8-chloro-6-oxooctanoic acid ethyl ester in the 8-chloro-6-oxooctanoic acid ethyl ester solution is 0.25-2.0:1, more preferably 0.4-0.6:1; the molar ratio of the phase transfer catalyst to the 8-chloro-6-oxooctanoic acid ethyl ester in the 8-chloro-6-oxooctanoic acid ethyl ester solution is 0.01-0.2:1, more preferably 0.02-0.1:1. Preferably, the reducing agent solution comprises an ammonia water solution with a concentration of 5-25 wt%.

Further, the reaction temperature of the continuous reduction reaction is 0-70 ℃, preferably 30-50 ℃; the continuous reduction reaction time is 0.5 to 4 hours, preferably 0.5 to 1.5 hours.

The product obtained by the continuous reduction reaction is subjected to continuous quenching treatment, and in some embodiments of the application, the continuous quenching treatment comprises continuously introducing the product obtained by the continuous reduction reaction into a kettle reactor to be mixed with a continuously introduced acid solution, preferably 5-37% hydrochloric acid. Preferably, the fourth continuous purification treatment comprises liquid separation, water washing and concentration to obtain the 6-hydroxy-8-chlorooctanoic acid ethyl ester.

In some exemplary embodiments of the present application, the continuous reduction reaction process is performed as follows: dissolving a reducing agent in 5-25% ammonia water, adding a certain amount of phase transfer catalyst to serve as a solution B, continuously reacting upstream to obtain an intermediate serving as a solution A, dilute hydrochloric acid serving as a solution C and water serving as a solution D; the solution A and the solution B are conveyed to a high-efficiency mixer according to a preset proportion through a feeding module, and materials enter a continuous columnar reactor for reaction after passing through the high-efficiency mixer; the reaction system enters a continuous quenching reaction kettle, passes through a feeding module and conveys a certain proportion of dilute hydrochloric acid solution to quench the reaction. The quenched system is in a liquid-liquid two-phase state, liquid separation is carried out through a continuous liquid separation module, the organic phase overflows to a subsequent continuous liquid separation module, a certain proportion of water is conveyed into the continuous liquid separation module through a feeding module, and the organic phase is washed. And (3) carrying out a continuous concentration module on the washed organic phase, concentrating the dichloroethane solvent, and recycling the dichloroethane solvent, wherein the residual oily matter is the crude product of the reduction product of the ethyl 6-hydroxy-8-chlorooctoate.

And (3) carrying out a second chlorination reaction on the prepared reduction product of the 6-hydroxy-8-chlorooctanoic acid ethyl ester, and obtaining the target product of the 6, 8-dichloro octanoic acid ethyl ester after fifth continuous purification treatment of the reaction liquid. Wherein the types of the second chlorinating agent, the fifth solvent and the fifth catalyst can be selected in the prior art, for example, the second chlorinating agent is selected from any one of thionyl chloride, oxalyl chloride and phosphorus trichloride; the fifth catalyst is selected from any one of DMF, pyridine and N, N-dimethylbenzylamine.

In some embodiments of the present application, to further increase the yield of the second chlorination reaction, the reaction temperature of the second chlorination reaction is 40 ℃ to 110 ℃; preferably 45-55 ℃; preferably, the reaction time of the second chlorination reaction is 0.5-4 hours; more preferably 0.5 to 1.5 hours.

Further, in the second chlorination reaction, the molar ratio of the second chlorinating agent to the reduction product of 6-hydroxy-8-chlorooctanoic acid ethyl ester is 1.0-2.0:1, preferably 1.1-1.3:1; the molar ratio of the fifth catalyst to the reduced product of 6-hydroxy-8-chloroethyl octanoate is 0.01-0.2:1, preferably 0.03-0.08:1, which is beneficial to further improving the yield of the target product and reducing the energy consumption.

In some exemplary embodiments of the application, the fifth continuous reactor is a continuous column reactor, which facilitates the discharge of the acid gas produced.

In some exemplary embodiments of the present application, the second chlorination process comprises: mixing the reduction product 6-hydroxy-8-chloroethyl octanoate obtained by the fourth continuous purification treatment, a fifth solvent and a fifth catalyst together to obtain a material E, conveying the material F as a second chlorinating agent to a high-efficiency mixer through a feeding module according to a preset proportion, and allowing the material to enter a continuous columnar reactor for reaction after passing through the high-efficiency mixer; removing the solvent and light components of the system after reaction through a continuous concentration module; and directly feeding the obtained heavy component into a continuous rectification module for continuous rectification to obtain the 6, 8-dichloro ethyl octanoate.

The advantageous effects that can be achieved by the present application will be further described below with reference to examples and comparative examples.

Example 1

According to the process flow chart shown in fig. 1, the full continuous synthesis of the monoethyl adipate is carried out, and the specific operation flow is as follows:

1. Mixing diethyl adipate, ethanol and p-toluenesulfonic acid according to a molar ratio of 0.8:3:0.1 to prepare a first mixed solution, storing the first mixed solution in a first storage tank 103, pumping the first mixed solution and toluene stored in a second storage tank 104 into the bottom of a column reactor 102 through a material beating module respectively, wherein the ratio of the mass flow rate of toluene to the input speed of raw material solid adipic acid is 2g/g;

2. The solid adipic acid in the solid adipic acid storage device 101 is continuously fed from the top of the column reactor 102 through a feeding module, the molar ratio of the adipic acid to the diethyl oxalate is 1.5:0.8, a condenser 107 is arranged at the top for water diversion reflux, the reaction temperature in the column reactor 102 is controlled to be 80 ℃, and the retention time is controlled to be 2 hours;

3. The reaction system in the column reactor 102 overflows from the upper part to the first continuous reaction kettle 108 for low-temperature termination, the temperature in the first continuous reaction kettle 108 is 5 ℃, and meanwhile, toluene stored in the third storage tank 105 is precooled to 0 ℃ by the precooling module 106 and then is fed to the first continuous reaction kettle 108 by the material beating module;

4. The system after termination is subjected to solid-liquid separation by a solid-liquid separation device 109, solid adipic acid is dried and then recovered, and filtrate is collected in a fourth storage tank 110;

5. Pumping filtrate and saturated sodium carbonate solution in a fourth storage tank 110 into a first continuous extraction module 111 through a beating module in proportion, performing alkali washing and liquid separation, wherein the upper layer is marked as an organic phase 1, and the lower layer is marked as a water phase 1;

6. The water phase 1 and toluene enter a second continuous extraction module 112 for washing and liquid separation, wherein the upper layer is marked as an organic phase 2, and the lower layer is marked as a water phase 2;

7. The organic phases 1 and 2 enter a continuous concentration module, toluene is cooled by a condenser and then is used mechanically, and concentrated solution diethyl adipate is recovered;

8. Hydrochloric acid and toluene enter a third continuous extraction module 113 through a continuous mixing module to be pickled with the water phase 2, wherein the upper layer is marked as an organic phase 3, and the lower layer is marked as the water phase 3;

9. The water phase 3 and toluene enter a fourth continuous extraction module 114 for washing and liquid separation, wherein the upper layer is marked as an organic phase 4, toluene and monoethyl adipate, and the lower layer is marked as a water phase 4 (wastewater phase);

10. The organic phases 3 and 4 enter a continuous concentration module, toluene is cooled by a condenser and then is used mechanically, concentrated solution (monoethyl adipate) is collected, and the yield of the monoethyl oxalate is 95%.

The 8-chloro-6-oxo-octanoic acid ethyl ester is prepared by the full continuous method of the adipic acid monoethyl ester prepared in the steps 1-10, and the specific operation process flow is as follows:

11. Pumping the adipic acid monoethyl ester, DMF and thionyl chloride into a tubular reactor through a material beating module according to the mol ratio of 1:0.2:1.05, wherein the reaction temperature is 40 ℃, the pressure is 1.2MPa, the retention time is 1h, and the yield of the 6-chloro-6-oxohexanoic acid ethyl ester is 98%;

12. The obtained reaction liquid and dichloroethane (the weight ratio of the dichloroethane to the reaction liquid is 8:1) are precooled to 0-5 ℃ by a precooling module and then enter a continuous reaction kettle for complexing, and solid aluminum chloride is continuously fed into the solution from the top of the reaction kettle by a feeding module, wherein the molar ratio of the aluminum chloride to the ethyl 6-chloro-6-oxohexanoate is 2.5:1;

13. pumping the complexing system and ethylene gas into the bottom of a gas-liquid reactor through a material beating module according to the mol ratio of ethylene to 6-chloro-6-oxohexanoate of 1.1:1, wherein a gas distributor is arranged at the bottom of the gas-liquid reactor, and the reaction temperature is 10 ℃ and the retention time is 10min;

14. The reaction system in the gas-liquid reactor overflows from the upper part to a continuous reaction kettle for low-temperature quenching, the temperature of the continuous reaction kettle is 10 ℃, and low-temperature water at 5 ℃ is supplemented by a material beating module and a precooling module;

15. The quenching system enters a liquid separation module to carry out continuous liquid separation, the left light phase is marked as a water phase 5 (waste water phase), and the right heavy phase is marked as an organic phase 5;

16. Pumping the organic phase 5 and saturated sodium bicarbonate solution into a continuous extraction module through a material beating module and a precooling module in proportion, performing alkaline washing and liquid separation, wherein the upper layer is marked as a water phase 6 (wastewater phase), and the lower layer is marked as the organic phase 6;

17. The organic phase 6 and water enter a continuous extraction module for washing and separating liquid, the upper layer is marked as water phase 7 (waste water phase), the lower layer is marked as organic phase 7 (dichloroethane and 8-chloro-6-oxo ethyl octoate), and the yield of the 8-chloro-6-oxo ethyl octoate is 88%.

The 8-chloro-6-oxo-ethyl octanoate solution prepared by the steps is applied to a process of fully continuously synthesizing 6-hydroxy-8-chloro-ethyl octanoate, and the specific process flow is as follows:

18. Dissolving potassium borohydride in 10% ammonia water, adding tetrabutylammonium bromide as solution B, and continuously reacting upstream to obtain an intermediate, namely 8-chloro-6-oxo-ethyl octoate solution as solution A, dilute hydrochloric acid solution with the concentration of 10% as solution C and water as solution D;

19. And conveying the solution A and the solution B to a high-efficiency mixer according to a preset proportion by a feeding module, wherein the molar ratio of potassium borohydride in the solution B to 6-hydroxy-8-chloroethyl octanoate in the solution A is 0.5:1, the molar ratio of tetrabutylammonium bromide in the solution B to 6-hydroxy-8-chloroethyl octanoate in the solution A is 0.02:1, and the materials enter a continuous column reactor to react after passing through the high-efficiency mixer, wherein the reaction temperature is 40 ℃, and the retention time is 1h.

20. The reaction system is subjected to continuous quenching of the reaction vessel, passed through the feed module and fed with solution C in order to quench the reaction.

21. The quenched system is in a liquid-liquid two-phase state, liquid separation is carried out through a continuous liquid separation module, the organic phase overflows to a subsequent continuous liquid separation module, and the solution D is conveyed through a feeding module to enter the continuous liquid separation module, so that the organic phase is washed.

22. The organic phase after water washing is subjected to a continuous concentration module, the dichloroethane solvent is concentrated for recycling, and the residual oily matter is the crude product of the reduction product of 6-hydroxy-8-chlorooctanoic acid ethyl ester, and the yield is 82.7%.

And (2) preparing a target product of 6, 8-dichloro ethyl octanoate by adopting a full continuous method from the 6-hydroxy-8-chloro ethyl octanoate prepared in the step (22), wherein the specific process flow is as follows:

23. Mixing the reduction product obtained in the last step with toluene and N, N-dimethylformamide to obtain a material E, conveying the material F by a feeding module according to a preset proportion to a high-efficiency mixer, wherein the molar ratio of the N, N-dimethylformamide to the thionyl chloride to the raw material 6-hydroxy-8-chloroethyl octanoate is 0.05:1.2:1, the mass ratio of toluene to the raw material 6-hydroxy-8-chloroethyl octanoate is 5:1, and feeding the material into a continuous column reactor to react after passing through the high-efficiency mixer, wherein the reaction temperature is 50 ℃, and the retention time is 0.5h.

24. The solvent and light components of the system after reaction are removed by a continuous concentration module.

25. And then the heavy component directly enters a continuous rectification module to carry out continuous rectification, so that the 6, 8-dichloro ethyl octanoate is obtained, the purity of the ethyl octanoate is 96%, and the yield of the reaction in the step is 83.6%.

Example 2

The difference from example 1 is that in step 1, diethyl adipate was not added. Correspondingly, the yield of monoethyl oxalate was 63%.

Example 3

The difference from example 1 is that in step2 the molar ratio of adipic acid to diethyl oxalate addition was 1:1. Correspondingly, the yield of monoethyl oxalate was 98%.

Example 4

The difference from example 1 is that in step2 the molar ratio of adipic acid to diethyl oxalate addition was 4:1. Correspondingly, the yield of monoethyl oxalate was 76%.

Example 5

The difference from example 1 is that in step 2, the reaction temperature was 50℃and the retention time was 4h. Correspondingly, the yield of monoethyl oxalate was 66%.

Example 6

The difference from example 1 is that in step 2, the reaction temperature is 150℃and the retention time is 2h. Correspondingly, the yield of monoethyl oxalate was 78%.

Example 7

The difference from example 1 is that in step 2, the reaction temperature is 80℃and the retention time is 4h. Correspondingly, the yield of monoethyl oxalate was 81%.

Example 8

The difference from example 1 is that the reaction temperature in step 11 is 70 ℃. Accordingly, the yield of ethyl 6-chloro-6-oxohexanoate was 76%.

Example 9

The difference from example 1 is that the reaction pressure in step 11 was 0.5MPa. Accordingly, the yield of ethyl 6-chloro-6-oxohexanoate was 64%.

Example 10

The difference from example 1 is that the reaction pressure in step 11 was 2MPa. Accordingly, the yield of ethyl 6-chloro-6-oxohexanoate was 98%.

Example 11

The difference from example 1 is that the reaction temperature in step 19 is 20℃and the retention time is 2h. Correspondingly, the yield of ethyl 6-hydroxy-8-chlorooctanoate was 80%.

Example 12

The difference from example 1 is that the reaction temperature in step 23 is 110 ℃. Correspondingly, the yield of ethyl 6, 8-dichloro-octanoate was 82%.

Comparative example 1

Sequentially adding adipic acid, diethyl adipate, ethanol, p-toluenesulfonic acid and toluene into a reaction kettle, wherein the molar ratio of the adipic acid to the diethyl adipate to the ethanol to the p-toluenesulfonic acid is 1.5:0.8:3:0.15, the mass ratio of the toluene to the adipic acid is 3:1, carrying out water diversion reflux at 105 ℃, reacting for 2 hours, stopping the reaction after water diversion is finished, adding toluene into the reaction liquid, cooling and stirring, carrying out low-temperature suction filtration, obtaining an filter cake which is adipic acid, and collecting filtrate. Alkalizing the filtrate with sodium carbonate solution, collecting lower water phase, washing, separating, collecting lower water phase, collecting upper organic phase, and rotary evaporating to obtain diethyl adipate. Acidifying the water phase with hydrochloric acid, adding toluene for washing, separating liquid, collecting an upper organic phase 1, adding toluene for washing again, separating liquid, collecting an upper organic phase 2, collecting the organic phases 1 and 2, and spin-drying to obtain the monoethyl adipate, wherein the yield of the monoethyl oxalate is 90%.

And adding the monoethyl adipate and the DMF into a reaction kettle, and dropwise adding the thionyl chloride under stirring at a process temperature, wherein the added monoethyl adipate, DMF and thionyl chloride are added through a stirring module according to a molar ratio of 1:0.2:1.2. After the dripping is finished, heating to 40 ℃ and preserving heat, reacting for 1.5h, and after the reaction is finished, evaporating thionyl chloride in a rotary way to obtain a crude product of the 6-chloro-6-oxohexanoate, wherein the yield of the 6-chloro-6-oxohexanoate is 96%.

Dissolving aluminum trichloride in dichloroethane, dropwise adding a crude product of 6-chloro-6-oxohexanoate at a low temperature, wherein the molar ratio of aluminum chloride to the ethyl 6-chloro-6-oxohexanoate is 2.5:1, preserving heat at 5 ℃ after the dropwise adding, introducing ethylene gas, slowly adding the reaction solution into hydrochloric acid after the reaction is finished, keeping the temperature in the dropwise adding process to be not more than 10 ℃, separating the solution, collecting a lower organic phase, and washing the organic phase twice to obtain the crude product, wherein the yield of the ethyl 8-chloro-6-oxooctanoate is 85%.

Dissolving potassium borohydride in a mixed solution of ammonia water and water, wherein the concentration of the ammonia water in the mixed solution is 10%, adding tetrabutylammonium bromide, and standing for standby, wherein the molar ratio of the tetrabutylammonium bromide to the potassium borohydride is 25:1. And (3) dropwise adding the standby potassium borohydride solution into the addition crude product solution at the temperature of 40 ℃, carrying out heat preservation reaction for 1h, adding water after the reaction is finished, washing and separating liquid, and collecting a lower organic phase. The organic phase is acidified by hydrochloric acid, and is stood for layering, and the lower organic phase is collected. The organic phase is washed once, separated, the organic phase is collected, the solvent is evaporated to dryness after the water is removed, and the reduced crude product is obtained, wherein the yield of the ethyl 6-hydroxy-8-chlorooctoate is 83%.

Adding 8-chloro-6-hydroxy ethyl octanoate, pyridine and toluene into a reaction kettle at 20 ℃, and dropwise adding thionyl chloride into the reaction kettle, wherein the molar ratio of N, N-dimethylformamide to thionyl chloride to the raw material 6-hydroxy-8-chloro ethyl octanoate is 0.05:1.2:1, and the mass ratio of toluene to the raw material 6-hydroxy-8-chloro ethyl octanoate is 5:1. After the dripping is finished, the temperature is raised to 50 ℃, the reaction is carried out for 1h, the solvent is dried by spin, toluene and water are added into the crude product, and the mixture is stirred and kept stand for liquid separation. Washing the organic phase with sodium bicarbonate aqueous solution, standing for separating liquid, performing reduced pressure distillation on the organic phase, and rectifying to obtain a pure product, wherein the yield of the reaction is 71.7%.

From the above description, it can be seen that the above embodiments of the present application achieve the following technical effects: the preparation method realizes the preparation of the 6, 8-dichloro ethyl octanoate by a full-continuous production process, well solves the problems of long operation period, low equipment utilization rate, different product quality, low automation degree and the like in the conventional intermittent production, ensures the uniformity of the product, has high automation degree and saves labor cost. Further, the continuous device adopted by the application has large specific surface area, is favorable for heat transfer, can reduce the temperature difference of the system, and can well solve the problem of yield reduction caused by more impurities generated by large temperature difference in the reaction process; on the other hand, the continuous device has small liquid holdup and high controllability, and remarkably improves the conversion rate of raw materials.

The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (11)

1. A method for producing ethyl 6, 8-dichloro octanoate, which is characterized by comprising the following steps:

continuously introducing adipic acid, ethanol, diethyl adipate, a first catalyst and a water-carrying agent into a first continuous reactor for esterification reaction, continuously introducing a reaction system obtained by the esterification reaction into a low-temperature device, terminating the reaction to obtain a first product system, performing solid-liquid separation on the first product system to obtain solid adipic acid and filtrate, and performing first continuous purification treatment on the filtrate to obtain monoethyl adipate;

Continuously introducing the monoethyl adipate, the first chlorinating agent and the second catalyst into a second continuous reactor to perform a first chlorination reaction to obtain a second product system, and continuously mixing the second product system, a third solvent and the third catalyst to obtain a continuous complexing system; introducing the continuous complexing system and ethylene gas into a continuous gas-liquid reactor for continuous addition reaction to obtain a third product system, and carrying out third continuous purification treatment on the third product system to obtain an 8-chloro-6-oxo-ethyl octanoate solution;

Introducing the 8-chloro-6-oxo-ethyl octanoate solution, a phase transfer catalyst and a reducing agent solution into a fourth continuous reactor for continuous reduction reaction, continuously quenching a product obtained by the continuous reduction reaction to obtain a fourth product system, and continuously purifying the fourth product system to obtain a reduction product of 6-hydroxy-8-chloro-ethyl octanoate;

And introducing the reduction product of 6-hydroxy-8-chloroethyl octanoate, a second chlorinating agent, a fifth solvent and a fifth catalyst into a fifth continuous reactor for a second chlorination reaction to obtain a second chlorination reaction product, and carrying out fifth continuous purification treatment on the second chlorination reaction product to obtain the target product of 6, 8-dichloroethyl octanoate.

2. The method for producing ethyl 6, 8-dichlorooctanoate according to claim 1, wherein said first continuous reactor is any one of a column reactor and a tubular reactor;

and/or the temperature of the low-temperature device is-10-30 ℃, more preferably 0-15 ℃,

And/or, the first continuous purification process comprises: and (3) alkali washing, acid washing and concentrating to obtain a concentrated solution of the monoethyl adipate.

3. The method for producing ethyl 6, 8-dichlorooctanoate according to claim 2, wherein said adipic acid is solid adipic acid, said first continuous reactor is a column reactor, said solid adipic acid is continuously fed from the top of said column reactor, and said ethanol, diethyl oxalate, first catalyst and water-carrying agent are continuously fed from the bottom of said column reactor;

and the reaction system obtained by the esterification reaction overflows from the upper part of the first continuous reactor to the low-temperature device, and a low-temperature first organic solvent is continuously added into the low-temperature device, wherein the first organic solvent comprises any one or more of toluene and methylene dichloride.

4. The method for producing ethyl 6, 8-dichlorooctoate according to any one of claims 1 to 3, wherein the temperature of the esterification reaction is 50 to 150 ℃;

and/or the reaction time of the esterification reaction is 0.5-4 h;

and/or the feeding speed of the adipic acid is 1.2-2.0 mol/h, the feeding speed of the diethyl adipate is 0.5-2.0 mol/h, the feeding speed of the ethanol is 1-5 mol/h, the feeding speed of the first catalyst is 0.01-0.5 mol/h, and the feeding speed of the water-carrying agent is 0.5-5 g/g.

5. The method for producing ethyl 6, 8-dichlorooctoate according to any one of claims 1 to 3, wherein the reaction temperature of the first chlorination reaction is 0 to 70 ℃, the reaction time is 0.5 to 4 hours, and the reaction pressure is 0.2 to 2mpa;

and/or, the second continuous reactor is a tubular reactor;

and/or the first chlorinating agent comprises any one or more of thionyl chloride, oxalyl chloride and triphosgene; the molar ratio of the first chlorinating agent to the monoethyl adipate is 1.0-1.5: 1, a step of;

and/or the second catalyst comprises one or more of DMF and pyridine, and the molar ratio of the second catalyst to the monoethyl adipate is 0.01-0.5:1.

6. The process for producing ethyl 6, 8-dichlorooctanoate according to claim 1, characterized in that said second product system, third solvent and third catalyst are mixed in a continuous tank reactor;

the third solvent comprises any one or more of dichloroethane and dichloromethane; the third catalyst comprises any one or more of aluminum chloride, ferric chloride and boron trifluoride;

The molar ratio of the third catalyst to the ethyl 6-chloro-6-oxohexanoate in the second product system is 1.5-4:1.

7. The process for the production of ethyl 6, 8-dichlorooctanoate according to claim 1 or 6, characterized in that said continuous complexation product system and said ethylene gas are fed into the bottom of said continuous gas-liquid reactor, the bottom of said gas-liquid reactor being provided with a gas distributor;

and/or the molar ratio of the ethylene gas to the ethyl 6-chloro-6-oxohexanoate in the second product system is 0.5-4:1;

and/or the third product system overflows from the upper part of the continuous gas-liquid reactor to a low-temperature quenching device to obtain a third quenched product system, and the third quenched product system is subjected to third continuous purification treatment;

and/or, the third continuous purification treatment comprises continuous alkaline washing and washing liquid separation by adopting a continuous extraction module to obtain the 8-chloro-6-oxo-octanoic acid ethyl ester solution.

8. The method for producing ethyl 6, 8-dichlorooctoate according to claim 1 or 6, wherein the temperature of the continuous addition reaction is-10-30 ℃ for 5-40 min.

9. The method for producing ethyl 6, 8-dichlorooctanoate according to claim 1, wherein said reducing agent comprises any one or more of potassium borohydride and sodium borohydride; the phase transfer catalyst comprises any one or more of tetrabutylammonium bromide and tetrabutylammonium chloride;

The mol ratio of the reducing agent to the 8-chloro-6-oxo-octanoic acid ethyl ester in the 8-chloro-6-oxo-octanoic acid ethyl ester solution is 0.25-2.0:1, and the mol ratio of the phase transfer catalyst to the 8-chloro-6-oxo-octanoic acid ethyl ester in the 8-chloro-6-oxo-octanoic acid ethyl ester solution is 0.01-0.2:1;

the reducer solution comprises ammonia water with the concentration of 5-25wt%;

The continuous quenching treatment comprises the steps of continuously introducing a product obtained by the continuous reduction reaction into a kettle type reactor to be mixed with a continuously introduced acid solution, wherein the acid solution is 5-37% hydrochloric acid;

The fourth continuous purification treatment comprises liquid separation, water washing and concentration to obtain the 6-hydroxy-8-chlorooctanoic acid ethyl ester.

10. The method for producing ethyl 6, 8-dichlorooctoate according to claim 1, wherein the reaction temperature of the continuous reduction reaction is 0 ℃ to 70 ℃; preferably 35-45 ℃,

The reaction time of the continuous reduction reaction is 0.5 to 4 hours, more preferably 0.5 to 1.5 hours.

11. The process for producing ethyl 6, 8-dichlorooctanoate according to claim 1, characterized in that said fifth continuous reactor is a continuous column reactor;

the reaction temperature of the second chlorination reaction is 40-110 ℃;

the reaction time of the second chlorination reaction is 0.5-4 hours.