Synthesis process of 6-chloro-2-hexanone

Abstract

The invention belongs to the technical field of synthesis of drug intermediates, and particularly relates to a synthesis process of 6-chloro-2-hexanone. The method comprises the following steps: cooling a solvent I, 1-methylcyclopentanol and an acid-binding agent, and introducing chlorine under heat-preservation stirring to obtain a mixed solution; adding a catalyst into the mixed solution, stirring, heating, keeping the temperature for reaction, and cooling to room temperature to obtain a reaction solution; filtering the reaction liquid to remove the catalyst to obtain filtrate; and carrying out reduced pressure distillation on the filtrate to remove the solvent I, cooling to room temperature, adding water and a solvent II, stirring, layering, extracting, washing, drying, filtering, and carrying out reduced pressure distillation to obtain the 6-chloro-2-hexanone. The method is high in yield, stable in process, high in operability and suitable for industrial production, and the prepared 6-chloro-2-hexanone is high in purity.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of pharmaceutical intermediates, and particularly relates to a synthesis process of 6-chloro-2-hexanone. Background Art

[0002] Pentoxifylline is an agent for improving cerebral circulation and peripheral vascular circulation disorders. It has the effects of dilating cerebral blood vessels and peripheral blood vessels, improving blood circulation in the brain and limbs, increasing blood flow in arteries and capillaries, reducing peripheral vascular resistance, but has no effect on blood pressure; it can also improve the deformability of red blood cells damaged by pathology, inhibit platelet aggregation, reduce blood viscosity, and improve the rheological properties of blood, thereby increasing the nutritional microcirculation in the ischemic area. In addition, pentoxifylline can also improve the oxidative capacity of hypoxic tissues. Pentoxifylline is mainly used for improving cerebral circulation after ischemic stroke, and can also be used for the treatment of peripheral circulation disorder diseases, inner ear circulation disorder diseases and ocular circulation disorder diseases, such as chronic obstructive vasculitis with intermittent claudication, diabetic retinal artery embolism, etc.

[0003] The chemical reaction equation for synthesizing pentoxifylline is as follows: .

[0004] 6-Chloro-2-hexanone is an important intermediate for synthesizing pentoxifylline. The synthesis of 6-chloro-2-hexanone usually uses 1,3-bromochloropropane and ethyl acetoacetate as raw materials, and through two-step reactions of ring formation and ring opening in the presence of a catalyst, and then the product is refined by column chromatography or rectification. The chemical reaction equation of this process is as follows: .

[0005] Synthesis of 1-(n-hexyl-5-one)-2-chlorobenzimidazole (Dubey, P. K; etal, Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry (2005), 44B(6), 1239-1242), Chinese Patent CN1082021A, Improvement of the synthesis process of 6-chloro-2-hexanone (Zhang Xiaohua, Hebei Chemical Industry, 1999(03), 21-22), etc. all describe this process, and the specific reagents and operations are more or less the same. This process requires two-step reactions, and each step has many side reactions and low product purity; the post-treatment is cumbersome and the total yield is not high.

[0006] Therefore, it is necessary to develop a synthesis process of 6-chloro-2-hexanone suitable for industrial production. Summary of the Invention

[0007] The object of the present invention is to provide a synthesis process of 6-chloro-2-hexanone, which has high yield, stable process, strong operability, is suitable for industrial production, and the prepared 6-chloro-2-hexanone has high purity.

[0008] The synthesis process of 6-chloro-2-hexanone described in the present invention comprises the following steps: (1) Cool down the solvent I, 1-methylcyclopentanol and the acid-binding agent, and introduce chlorine gas under stirring while maintaining the temperature to obtain a mixed solution; (2) Add a catalyst to the mixed solution, stir and heat up, carry out the reaction while maintaining the temperature, and cool down to room temperature to obtain a reaction solution; (3) Filter the reaction solution to remove the catalyst to obtain a filtrate; (4) After distilling off the solvent I under reduced pressure, cool down to room temperature, add water and the solvent II, stir, separate the layers, extract, wash, dry, filter, and carry out reduced pressure distillation to obtain 6-chloro-2-hexanone.

[0009] In step (1), the solvent I is acetone or acetonitrile.

[0010] In step (1), the acid-binding agent is triethylamine.

[0011] In step (1), the mass ratio of 1-methylcyclopentanol, chlorine gas and the acid-binding agent is 1:0.746 - 0.78:1.06 - 1.114; the ratio of 1-methylcyclopentanol to the solvent I is 1:8 - 12, where 1-methylcyclopentanol is in g and the solvent I is in ml.

[0012] In step (1), cool down to 0 - 5°C, maintain the temperature at 0 - 5°C, and the introduction time is 0.5 - 1 hour.

[0013] In step (2), the catalyst is molybdenum trioxide.

[0014] In step (2), the mass ratio of the catalyst to 1-methylcyclopentanol is 0.072 - 0.216:1.

[0015] In step (2), the temperature for the reaction while maintaining the temperature is 70 - 90°C, and the reaction time while maintaining the temperature is 8 - 12 hours.

[0016] In step (4), the temperature for distilling off the solvent I under reduced pressure is 50 - 70°C.

[0017] In step (4), the solvent II is one or more of cyclohexane, n-hexane or n-heptane.

[0018] In step (4), the temperature for reduced pressure distillation is not higher than 80°C, and the vacuum degree for reduced pressure distillation is not less than -0.095 MPa.

[0019] In step (4), after the solvent I in the filtrate is distilled off under reduced pressure, the temperature is lowered to room temperature, water and solvent II are added, and the mixture is stirred for 5 - 10 minutes and then left to stand for liquid separation; the organic layer is separated, and the aqueous layer is extracted twice with solvent II; the organic layers are combined, washed once with a saturated aqueous sodium bicarbonate solution and then once with purified water; a drying agent is added to the organic layer, and the mixture is stirred and dried for 0.5 - 1.5 hours, the drying agent is filtered off, and the filtrate is distilled under reduced pressure to obtain 6-chloro-2-hexanone; wherein, the drying agent is anhydrous magnesium sulfate or anhydrous sodium sulfate.

[0020] The chemical reaction equation of the present invention is as follows: 。

[0021] After chlorine gas is introduced in the present invention, most of the chlorine gas exists in the solution in the form of chlorine molecules. During the heating reaction process, 1-methylcyclopentanol first forms an intermediate state ,releasing H + ,H + whose acidity is weakened by an acid-binding agent, and then the intermediate state undergoes ring opening under the action of a catalyst to obtain 6-chloro-2-hexanone.

[0022] The present invention uses 1-methylcyclopentanol as the starting material, and in the presence of a catalyst and an acid-binding agent, performs oxidative chlorination with chlorine gas, and obtains 6-chloro-2-hexanone through extraction, washing, and distillation under reduced pressure.

[0023] The beneficial effects of the present invention are as follows: (1) The present invention adopts a one-step reaction, simplifies the reaction steps, and shortens the reaction time.

[0024] (2) The raw materials used in the present invention are easily available and inexpensive, avoiding the use of bromides, and being economical and environmentally friendly.

[0025] (3) The 6-chloro-2-hexanone synthesized by the present invention has a high yield and high purity.

[0026] (4) The process of the present invention is stable, highly operable, and suitable for industrial production. Description of the Drawings

[0027] Figure 1 is the GC chromatogram of 6-chloro-2-hexanone in Example 1. Detailed Embodiments

[0028] The present invention will be further described below in conjunction with examples.

[0029] Example 1 (1) Add 150 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine to a reaction flask, lower the temperature to 0 °C, and slowly introduce 11.5 g of chlorine gas under stirring while maintaining the temperature at 0 °C for 1 hour to obtain a mixed solution; (2) Transfer the mixed solution into a high-pressure reactor lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the reactor lid, close the inlet and outlet valves, stir and heat up to 80 °C, keep the temperature for reaction for 10 hours, cool down to room temperature, exhaust the gas, and then open the reactor lid to obtain the reaction solution; (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain the filtrate; (4) Evaporate acetone from the filtrate under reduced pressure at 60 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 5 minutes, let it stand for layer separation, separate the organic layer, extract the aqueous layer twice with 50 ml × 2 of n-hexane, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1 hour, filter, and evaporate the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 99.13%, yield: 84.1%. The GC spectrum of 6-chloro-2-hexanone is shown in Figure 1 , and the GC data are shown in Table 1.

[0030]

[0031] Example 2 (1) Add 150 ml of acetone, 15.0 g of 1-methylcyclopentanol and 15.9 g of triethylamine into a reaction flask, cool down to 5 °C, and slowly introduce 11.2 g of chlorine gas under stirring and keeping the temperature at 5 °C for 0.5 hour to obtain a mixed solution; (2) Transfer the mixed solution into a high-pressure reactor lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the reactor lid, close the inlet and outlet valves, stir and heat up to 90 °C, keep the temperature for reaction for 10 hours, cool down to room temperature, exhaust the gas, and then open the reactor lid to obtain the reaction solution; (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain the filtrate; (4) Evaporate acetone from the filtrate under reduced pressure at 70 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 8 minutes, let it stand for layer separation, separate the organic layer, extract the aqueous layer twice with 50 ml × 2 of n-hexane, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1.5 hours, filter, and evaporate the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.52%, yield: 82.7%.

[0032] Example 3 (1) Add 150 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 16.7 g of triethylamine to a reaction flask. Cool the temperature to 2 °C, and slowly introduce 11.7 g of chlorine gas under stirring at 2 °C for 0.8 hours to obtain a mixed solution. (2) Transfer the mixed solution to a high-pressure reaction kettle lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 80 °C, keep the temperature for reaction for 10 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Distill off acetone from the filtrate under reduced pressure at 70 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 10 minutes, let it stand for liquid separation, separate the organic layer, extract the aqueous layer twice with 50 ml × 2 of n-hexane, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1 hour, filter, and distill off the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.55%, yield: 83.5%.

[0033] Example 4 (1) Add 180 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine to a reaction flask. Cool the temperature to 3 °C, and slowly introduce 11.5 g of chlorine gas under stirring at 3 °C for 0.5 hours to obtain a mixed solution. (2) Transfer the mixed solution to a high-pressure reaction kettle lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 80 °C, keep the temperature for reaction for 12 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Distill off acetone from the filtrate under reduced pressure at 60 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of cyclohexane, stir for 5 minutes, let it stand for liquid separation, separate the organic layer, extract the aqueous layer twice with 50 ml × 2 of cyclohexane, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1 hour, filter, and distill off the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.95%, yield: 84.7%.

[0034] Example 5 (1) Add 120 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 15.9 g of triethylamine into a reaction flask. Cool the temperature to 0 °C, and slowly introduce 11.2 g of chlorine gas while stirring at 0 °C for 1 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 90 °C, keep the temperature for reaction for 12 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Distill off acetone from the filtrate under reduced pressure at 60 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 10 minutes, let it stand for layering, separate the organic layer. Extract the aqueous layer twice with 50 ml of n-hexane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1.5 hours, filter, and distill off the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.48%, yield: 83.1%.

[0035] Example 6 (1) Add 150 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine into a reaction flask. Cool the temperature to 2 °C, and slowly introduce 11.5 g of chlorine gas while stirring at 2 °C for 1 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 3.24 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 70 °C, keep the temperature for reaction for 12 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Distill off acetone from the filtrate under reduced pressure at 50 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 5 minutes, let it stand for layering, separate the organic layer. Extract the aqueous layer twice with 50 ml of n-hexane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 0.5 hours, filter, and distill off the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.73%, yield: 84.3%.

[0036] Example 7 (1) Add 150 ml of acetone, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine into a reaction flask. Cool the temperature to 0 °C, and slowly introduce 11.5 g of chlorine gas under stirring at 0 °C for 0.5 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 1.08 g of molybdenum trioxide, fasten the kettle cover, close the inlet and outlet valves, stir and heat up to 90 °C, keep the temperature for reaction for 12 hours, cool down to room temperature, exhaust the gas, and then open the kettle cover to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Evaporate acetone from the filtrate under reduced pressure at 50 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of cyclohexane, stir for 10 minutes, let it stand for layer separation, separate the organic layer, extract the aqueous layer twice with 50 ml of cyclohexane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous sodium sulfate, stir and dry for 1.5 hours, filter, and evaporate the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.37%, yield: 83.9%.

[0037] Example 8 (1) Add 150 ml of acetonitrile, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine into a reaction flask. Cool the temperature to 5 °C, and slowly introduce 11.5 g of chlorine gas under stirring at 5 °C for 0.8 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 2.16 g of molybdenum trioxide, fasten the kettle cover, close the inlet and outlet valves, stir and heat up to 80 °C, keep the temperature for reaction for 10 hours, cool down to room temperature, exhaust the gas, and then open the kettle cover to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Evaporate acetonitrile from the filtrate under reduced pressure at 60 °C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-hexane, stir for 10 minutes, let it stand for layer separation, separate the organic layer, extract the aqueous layer twice with 50 ml of n-hexane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous sodium sulfate, stir and dry for 1 hour, filter, and evaporate the solvent from the filtrate under reduced pressure at 80 °C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.65%, yield: 83.4%.

[0038] Example 9 (1) Add 150 ml of acetonitrile, 15.0 g of 1-methylcyclopentanol, and 16.7 g of triethylamine into a reaction flask. Cool the temperature to 2°C, and slowly introduce 11.7 g of chlorine gas under stirring at 2°C for 1 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 1.08 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 90°C, keep the temperature for reaction for 12 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Evaporate acetonitrile from the filtrate under reduced pressure at 70°C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-heptane, stir for 5 minutes, let it stand for layer separation, separate the organic layer. Extract the aqueous layer twice with 50 ml of n-heptane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous magnesium sulfate, stir and dry for 1 hour, filter, and evaporate the solvent from the filtrate under reduced pressure at 80°C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.42%, yield: 82.9%.

[0039] Example 10 (1) Add 180 ml of acetonitrile, 15.0 g of 1-methylcyclopentanol, and 16.4 g of triethylamine into a reaction flask. Cool the temperature to 0°C, and slowly introduce 11.5 g of chlorine gas under stirring at 0°C for 0.5 hour to obtain a mixed solution. (2) Transfer the mixed solution into a high-pressure reaction kettle lined with tetrafluoroethylene, add 3.24 g of molybdenum trioxide, fasten the kettle lid, close the inlet and outlet valves, stir and heat up to 80°C, keep the temperature for reaction for 8 hours, cool down to room temperature, exhaust the gas, and then open the kettle lid to obtain a reaction solution. (3) Filter the reaction solution to remove the catalyst molybdenum trioxide to obtain a filtrate. (4) Evaporate acetonitrile from the filtrate under reduced pressure at 60°C. After there is basically no distillate, cool down to room temperature, add 50 ml of water and 50 ml of n-heptane, stir for 8 minutes, let it stand for layer separation, separate the organic layer. Extract the aqueous layer twice with 50 ml of n-heptane each time, combine the organic layers, wash once with 50 ml of saturated sodium bicarbonate aqueous solution, then wash once with 50 ml of purified water, add 10 g of anhydrous sodium sulfate, stir and dry for 1.5 hours, filter, and evaporate the solvent from the filtrate under reduced pressure at 80°C (vacuum degree: -0.095 MPa) to obtain 6-chloro-2-hexanone, purity (GC): 98.87%, yield: 83.7%.

[0040] The present invention has been described in detail in conjunction with the embodiments, but the above content is only the preferred embodiment of the present invention and should not be considered as limiting the scope of implementation of the present invention. All equivalent changes and improvements made according to the scope of the application of the present invention should still fall within the scope covered by the patent of the present invention.

Claims

1. A synthesis process of 6-chloro-2-hexanone, characterized in that It includes the following steps: (1) Cool the solvent I, 1-methylcyclopentanol and the acid-binding agent, and introduce chlorine gas while stirring and maintaining the temperature to obtain a mixed solution; (2) Add a catalyst to the mixed solution, stir and heat up, maintain the reaction, and cool to room temperature to obtain a reaction solution; (3) Filter the reaction solution to remove the catalyst to obtain a filtrate; (4) After distilling off the solvent I under reduced pressure, cool to room temperature, add water and solvent II, stir, separate the layers, extract, wash, dry, filter, and distill under reduced pressure to obtain 6-chloro-2-hexanone.

2. The synthesis process of 6-chloro-2-hexanone according to claim 1, wherein In step (1), the solvent I is acetone or acetonitrile.

3. The synthesis process of 6-chloro-2-hexanone according to claim 1, wherein In step (1), the acid-binding agent is triethylamine.

4. The synthesis process of 6-chloro-2-hexanone according to claim 1, wherein In step (1), the mass ratio of 1-methylcyclopentanol, chlorine gas to the acid-binding agent is 1:0.746 - 0.78:1.06 - 1.114; the ratio of 1-methylcyclopentanol to the solvent I is 1:8 - 12, where 1-methylcyclopentanol is in g and the solvent I is in ml.

5. The synthesis process of 6-chloro-2-hexanone according to claim 1, wherein In step (1), cool to 0 - 5 °C, maintain the temperature at 0 - 5 °C, and the introduction time is 0.5 - 1 hour.

6. The synthesis process of 6-chloro-2-hexanone according to claim 1, characterized in that In step (2), the catalyst is molybdenum trioxide.

7. The synthesis process of 6-chloro-2-hexanone according to claim 1, wherein In step (2), the mass ratio of the catalyst to 1-methylcyclopentanol is 0.072 - 0.216:

1.

8. The synthesis process of 6-chloro-2-hexanone according to claim 1, characterized in that In step (2), the temperature for maintaining the reaction is 70 - 90 °C, and the time for maintaining the reaction is 8 - 12 hours.

9. The synthesis process of 6-chloro-2-hexanone according to claim 1, characterized in that In step (4), the temperature for distilling off the solvent I under reduced pressure is 50 - 70 °C, the solvent II is one or several of cyclohexane, n-hexane or n-heptane; the temperature for distilling under reduced pressure is not higher than 80 °C, and the vacuum degree for distilling under reduced pressure is not less than -0.095 MPa.

10. The synthesis process of 6-chloro-2-hexanone according to claim 1, characterized in that In step (4), after distilling off the solvent I from the filtrate under reduced pressure, cool to room temperature, add water and solvent II, stir for 5 - 10 minutes, and let it stand to separate the layers; separate the organic layer, and extract the aqueous layer twice with the solvent II; combine the organic layers, wash once with a saturated aqueous sodium bicarbonate solution and then once with purified water; add a drying agent to the organic layer, stir and dry for 0.5 - 1.5 hours, filter to remove the drying agent, and distill under reduced pressure to obtain 6-chloro-2-hexanone; where the drying agent is anhydrous magnesium sulfate or anhydrous sodium sulfate.

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