A method for preparing ethyl 6,8-dichlorooctanoate based on cathode selective reduction

Abstract

This invention provides a method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction, belonging to the field of organic synthesis technology. The preparation method includes the following steps: mixing ethyl 6-carbonyl-8-chlorooctanoate with a non-aqueous solvent and a supporting electrolyte, and performing cathodic reduction in a constant current mode to obtain ethyl 6-hydroxy-8-chlorooctanoate; the supporting electrolyte is one of tetrabutylammonium tetrafluoroborate, tetraethylammonium p-toluenesulfonate, or lithium perchlorate; and the cathodic current density of the cathodic reduction is 3–15 mA / cm². 2 The 6-hydroxy-8-chlorooctanoic acid ethyl ester was dissolved in an organic solvent, and then a photocatalyst and a chlorine source were added. Following irradiation with visible light, a chlorination reaction was carried out to obtain 6,8-dichlorooctanoic acid ethyl ester. This invention provides a technical solution that preferentially converts the 6-carbonyl group to a hydroxyl group while effectively suppressing the side reaction of the 8-chlorination structure, thereby improving the retention rate of the 8-chlorination structure.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction. Background Technology

[0002] Ethyl 6,8-dichlorooctanoate is an important compound for the preparation of lipoic acid and related intermediates. In existing technologies, this type of compound is typically prepared through steps such as carbon chain construction, carbonyl conversion, and hydroxyl chlorination. Among these steps, the conversion of the carbonyl group at the 6-position to the hydroxyl group at the 6-position is one of the key steps affecting the efficiency of subsequent chlorination.

[0003] For ethyl 6-carbonyl-8-chlorooctanoate, its molecule contains both a reductive carbonyl group at the 6-position and a chlorinated aliphatic chain at the 8-position, which is sensitive to reaction conditions. In existing technologies, the conversion of the carbonyl group at the 6-position to the hydroxyl group typically employs methods such as chemically selective reduction, catalytic hydrogenation, or enzyme-catalyzed reduction.

[0004] For example, Chinese patent application CN115992107A, entitled "A Ketoreductase and Its Application," discloses the application of a ketoreductase in the in vitro biosynthesis of (R)-6-hydroxy-8-chlorooctanoate ethyl ester. This application utilizes a ketoreductase as a biocatalyst to convert 8-chloro-6-oxooctanoate ethyl ester to (R)-6-hydroxy-8-chlorooctanoate ethyl ester, exhibiting a certain degree of chiral selectivity. However, for 6-carbonyl-8-chlorooctanoate ethyl ester substrates containing an 8-position chlorination structure, it is still necessary to ensure the carbonyl conversion rate while also considering the retention rate of the 8-position chlorination structure, the stability of the reaction system, and the continuity of subsequent chlorination steps.

[0005] Although it is known in the art that carbonyl groups can be reduced electrochemically, the reaction behavior of substrates such as ethyl 6-carbonyl-8-chlorooctanoate, which contains both carbonyl and chlorination-sensitive sites, differs significantly from that of ordinary carbonyl substrates. Under conventional cathodic reduction conditions, in addition to the reduction of the target carbonyl group, competitive side reactions related to the 8-C-Cl bond may occur, such as reductive dechlorination, cleavage, associated elimination, or structural damage caused by changes in the local reaction environment. The risk of these side reactions is further increased, especially under conditions of high cathode overpotential, high current density, excessively strong proton donors, or high water content.

[0006] Therefore, the existing technology lacks a preparation method that can achieve a high 6-carbonyl-8-chlorooctanoate ethyl ester substrate while maintaining 6-hydroxy selectivity, 8-chlorination structure retention, and seamless transition of subsequent chlorination steps at a high 6-carbonyl conversion rate. Summary of the Invention

[0007] In view of this, the present invention provides a method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction, which achieves preferential conversion of the carbonyl group at the 6-position to the hydroxyl group while effectively suppressing the side reaction of the chlorinated structure at the 8-position and improving the retention rate of the chlorinated structure at the 8-position.

[0008] To achieve the above objectives, the present invention provides a method for preparing ethyl 6,8-dichlorooctanoate based on cathode selective reduction, comprising the following steps:

[0009] (1) Ethyl 6-carbonyl-8-chlorooctanoate is mixed with a non-aqueous solvent and a supporting electrolyte, and cathodic reduction is performed in a constant current mode to obtain ethyl 6-hydroxy-8-chlorooctanoate; the supporting electrolyte is one of tetrabutylammonium tetrafluoroborate, tetraethylammonium p-toluenesulfonate, or lithium perchlorate, and the cathodic current density of the cathodic reduction is 3–15 mA / cm. 2 ; (2) After dissolving the 6-hydroxy-8-chlorooctanoic acid ethyl ester in an organic solvent, a photocatalyst and a chlorine source are added, and then chlorination is carried out by visible light irradiation to obtain 6,8-dichlorooctanoic acid ethyl ester.

[0010] The solution provided by the present invention uses a cathodic reduction method to control the conditions to reduce the carbonyl group at the 6-position and suppress the dechlorination or other side reactions of the chlorinated structure at the 8-position, thereby improving the retention rate of the chlorinated structure at the 8-position while preferentially converting the carbonyl group at the 6-position to the hydroxyl group.

[0011] Optionally, the non-aqueous solvent is one or a combination of two or more of ethanol, isopropanol, and acetonitrile.

[0012] Optionally, the non-aqueous solvent is a non-aqueous mixed solvent obtained by mixing an alcohol solvent and acetonitrile, wherein the alcohol solvent is ethanol or isopropanol.

[0013] The present invention uses a non-aqueous solvent to suppress the occurrence of dechlorination side reactions and improve the retention rate of the 8-position chlorinated structure.

[0014] Optionally, the cathode material for cathode reduction is one of carbon felt, glassy carbon board, or nickel foam; the anode material for cathode reduction is one of graphite or titanium-based inert anode.

[0015] Optionally, the titanium-based inert anode material is a titanium-based metal oxide coated anode.

[0016] Optionally, the cathode reduction occurs in a diaphragm-free electrolytic reactor.

[0017] Optionally, the cathode reduction time is 1-5 hours; the cathode reduction temperature is 20-50°C; and the cathode current density is 5-10 mA / cm². 2 .

[0018] In the cathodic reduction reaction of this invention, if the current density is too low, the reaction efficiency will be insufficient; if the current density is too high, the side reactions on the electrode surface will be aggravated, resulting in a decrease in the retention rate of the 8-position chlorinated structure.

[0019] This invention employs a constant current mode, which is simple to operate, has low equipment cost, controllable reaction rate, and facilitates process scale-up.

[0020] Optionally, the cathode reduction temperature is 25~35℃.

[0021] Optionally, the supporting electrolyte is tetrabutylammonium tetrafluoroborate.

[0022] The supporting electrolyte used in this invention helps to improve the conductivity of non-aqueous systems and reduce side reactions caused by uneven local electric fields and mass transfer.

[0023] Optionally, the photocatalyst is Ru(bpy)3Cl2, and the chlorine source is N-chlorosuccinimide.

[0024] Optionally, the organic solvent is dichloromethane.

[0025] Optionally, the visible light is a 395 nm light source.

[0026] Optionally, the 6-hydroxy-8-chlorooctanoate intermediate obtained in step (1) has a carbonyl conversion of not less than 95.0%, a 6-hydroxy selectivity of not less than 92.0%, and a chlorination structure retention of not less than 93.0%.

[0027] Optionally, the GC purity of the ethyl 6,8-dichlorooctanoate obtained in step (2) shall not be less than 98.0%.

[0028] This invention also provides a method for preparing ethyl 6-hydroxy-8-chlorooctanoate, comprising the following steps: Ethyl 6-carbonyl-8-chlorooctanoate was mixed with a non-aqueous solvent and a supporting electrolyte, and cathodic reduction was performed in a constant current mode to obtain ethyl 6-hydroxy-8-chlorooctanoate. The supporting electrolyte was tetrabutylammonium tetrafluoroborate, tetraethylammonium p-toluenesulfonate, or lithium perchlorate, and the cathodic current density of the cathodic reduction was 3–15 mA / cm². 2 .

[0029] The above-described technical solution of the present invention has at least the following beneficial effects: The preparation method provided by this invention establishes a cathodic selective reduction process system for ethyl 6-carbonyl-8-chlorooctanoate, a specific substrate containing a sensitive chlorination structure at the 8-position. Through the synergistic matching of a non-aqueous medium, a supporting electrolyte, and a suitable current density window, the method achieves preferential reduction and high conversion of the 6-carbonyl group while effectively suppressing dechlorination and related side reactions at the 8-position, thus improving the retention rate of the 8-position chlorination structure. The resulting ethyl 6-hydroxy-8-chlorooctanoate intermediate has high purity, which is beneficial for efficient connection with subsequent chlorination steps. The process conditions of this invention are relatively mild, with low post-processing burden, making it suitable for industrial implementation. Attached Figure Description

[0030] Figure 1 This is a GC purity test result of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate of Example 1 of this invention. Figure 2 This is a GC purity test result of ethyl 6,8-dichlorooctanoate in the crude product of Example 1 of the present invention. Figure 3 This is a GC purity test result of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate of Comparative Example 4 of this invention. Figure 4 This is a GC purity test result of ethyl 6,8-dichlorooctanoate in the crude product of Comparative Example 4 of this invention. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will be described in conjunction with the accompanying drawings of the embodiments of the present invention. Figures 1-4 The technical solutions of the embodiments of the present invention will be clearly and completely described herein. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0032] Unless otherwise stated, the detection methods in the various embodiments and comparative examples are as follows: (1) 6-carbonyl conversion rate: The remaining amount of 6-carbonyl-8-chlorooctanoate in the reaction solution was quantitatively analyzed by gas chromatography, and the 6-carbonyl conversion rate was calculated by combining the correction factor.

[0033] (2) 6-hydroxy selectivity: Ethyl 6-hydroxy-8-chlorooctanoate was quantitatively analyzed by gas chromatography, and peak assignment and content were confirmed by combining standard samples, control samples and / or correction factors. The 6-hydroxy selectivity was then calculated based on the conversion of raw materials.

[0034] (3) Retention rate of 8-position chlorinated structure: The target product and related components retaining the 8-position chlorinated structure were quantitatively analyzed by gas chromatography, and the 8-position chlorinated structure retention rate was calculated after peak assignment confirmation by standard sample, control sample and / or gas chromatography-mass spectrometry.

[0035] (4) GC purity of intermediate: determined by gas chromatography peak area normalization method; the sample was injected after being diluted with organic solvent, and the corresponding solvent peak in the blank control was subtracted and normalized.

[0036] Example 1 Step (1): In a 500 mL diaphragm-free electrolytic reactor, add 50 g of ethyl 6-carbonyl-8-chlorooctanoate, 150 mL of ethanol, 100 mL of acetonitrile, and 12 g of tetrabutylammonium tetrafluoroborate, and stir to form a homogeneous reaction system. Electrolysis is performed at 35 °C using a constant current mode with carbon felt as the cathode and graphite plate as the anode, and the cathode current density is controlled at 7 mA / cm² for 2.5 h. After the reaction, remove some of the solvent under reduced pressure, add an appropriate amount of deionized water, extract with dichloromethane, wash the organic phase with saturated brine, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain 46.9 g of crude intermediate. Gas chromatography analysis showed that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 94.4%. (See gas chromatogram). Figure 1 .

[0037] Analysis of the intermediate obtained in step (1) showed that the carbonyl group at position 6 had a conversion rate of 96.8%, the selectivity of 6-hydroxyl group was 94.6%, and the retention rate of chlorinated structure at position 8 was 95.2%, indicating that the carbonyl group at position 6 in the substrate had been selectively reduced to hydroxyl group, while the chlorinated structure at position 8 was effectively retained.

[0038] Step (2): 46.9 g of the above crude intermediate was dissolved in 250 mL of dichloromethane, and 31.7 g of N-chlorosuccinimide and 2 mol% Ru(bpy)3Cl2 of the crude intermediate were added. The reaction was carried out at 30 °C for 3 h under 395 nm LED light irradiation. After the reaction was completed, the product was washed with 5% sodium thiosulfate aqueous solution and then washed with saturated sodium bicarbonate aqueous solution to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain 44.2 g of the final crude product. The yield of step (2) was 91.5%. The GC purity of 6,8-dichlorooctanoate was 98.7% as determined by gas chromatography. The gas chromatogram is shown in [reference needed]. Figure 2 .

[0039] Example 2 Step (1): In a 500 mL diaphragm-free electrolytic reactor, add 50 g of ethyl 6-carbonyl-8-chlorooctanoate, 150 mL of ethanol, 100 mL of acetonitrile, and 12 g of lithium perchlorate, and stir to form a homogeneous reaction system. Electrolysis is performed at 50 °C using a glassy carbon plate as the cathode and a titanium-based metal oxide coated anode as the anode, in constant current mode. The cathode current density is controlled at 5 mA / cm², and the reaction is carried out for 5 h. After the reaction, some solvent is removed under reduced pressure, an appropriate amount of deionized water is added, and the mixture is extracted with dichloromethane. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and then the solvent is removed under reduced pressure to obtain the crude intermediate. Gas chromatography analysis shows that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate is 92.9%.

[0040] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at the 6-position was 96.1%, the selectivity of the 6-hydroxy group was 93.4%, and the retention rate of the chlorinated structure at the 8-position was 94.3%, indicating that the glassy carbon cathode can also achieve selective reduction of the carbonyl group at the 6-position and maintain a good retention effect of the chlorinated structure at the 8-position.

[0041] Step (2): The above crude intermediate was dissolved in 250 mL of dichloromethane, and 31.7 g of N-chlorosuccinimide and 2 mol% Ru(bpy)3Cl2 of the crude intermediate were added. The reaction was carried out at 20 °C for 4 h under 395 nm LED light source irradiation. After the reaction was completed, the product was washed with 5% sodium thiosulfate aqueous solution and then washed with saturated sodium bicarbonate aqueous solution to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude final product. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 98.2%, and the yield of step (2) was 90.3%.

[0042] Example 3 Step (1): In a 500 mL diaphragm-free electrolytic reactor, add 50 g of ethyl 6-carbonyl-8-chlorooctanoate, 150 mL of ethanol, 100 mL of acetonitrile, and 12 g of tetrabutylammonium tetrafluoroborate, and stir to form a homogeneous reaction system. Electrolysis is performed at 20 °C using nickel foam as the cathode and graphite plate as the anode in constant current mode, with the cathode current density controlled at 10 mA / cm², for 2 h. After the reaction, remove some of the solvent under reduced pressure, add an appropriate amount of deionized water, extract with dichloromethane, wash the organic phase with saturated brine, dry with anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure to obtain the crude intermediate. Gas chromatography analysis showed that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 92.6%.

[0043] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at position 6 was 96.9%, the selectivity of the 6-hydroxyl group was 93.1%, and the retention rate of the chlorinated structure at position 8 was 93.8%. This indicates that the nickel foam cathode can also achieve good reduction performance in the process system of this invention. The carbonyl group at position 6 in the substrate has been selectively reduced to the hydroxyl group, while the chlorinated structure at position 8 is effectively maintained. The adjustments to the conditions in Examples 1 and 2 demonstrate that this invention is not limited to a single carbon-based cathode, but emphasizes the synergistic matching of cathode materials, dielectrics, electrolytes, and electrochemical windows.

[0044] Step (2): The above crude intermediate was dissolved in 250 mL of dichloromethane, and 31.7 g of N-chlorosuccinimide and 2 mol% Ru(bpy)3Cl2 of the crude intermediate were added. The reaction was carried out at 25 °C for 3 h under 395 nm LED light source irradiation. After the reaction was completed, the product was washed with 5% sodium thiosulfate aqueous solution and then washed with saturated sodium bicarbonate aqueous solution to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude final product. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 98.0%, and the yield of step (2) was 89.8%.

[0045] Example 4 Step (1): In a 500 mL diaphragm-free electrolytic reactor, add 50 g of ethyl 6-carbonyl-8-chlorooctanoate, 150 mL of isopropanol, 100 mL of acetonitrile, and 12 g of tetraethyl toluenesulfonate, and stir to form a homogeneous reaction system. Electrolysis is performed at 25 °C using a constant current mode with carbon felt as the cathode and graphite plate as the anode, and the cathode current density is controlled at 15 mA / cm² for 1 h. After the reaction, some solvent is removed under reduced pressure, and an appropriate amount of deionized water is added. Extraction is performed with dichloromethane, and the organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and then the solvent is removed under reduced pressure to obtain the crude intermediate. Gas chromatography analysis showed that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 92.3%.

[0046] Analysis of the intermediate obtained in step (1) showed that the carbonyl group at position 6 had a conversion rate of 95.7%, the selectivity of 6-hydroxyl group was 92.8%, and the retention rate of the chlorinated structure at position 8 was 94.0%, indicating that the carbonyl group at position 6 in the substrate had been selectively reduced to hydroxyl group, while the chlorinated structure at position 8 was effectively retained.

[0047] Step (2): The above crude intermediate was dissolved in 250 mL of dichloromethane, and 31.7 g of N-chlorosuccinimide and 2 mol% Ru(bpy)3Cl2 of the crude intermediate were added. The reaction was carried out at 28 °C for 3 h under 395 nm LED light source irradiation. After the reaction was completed, the product was washed with 5% sodium thiosulfate aqueous solution and then washed with saturated sodium bicarbonate aqueous solution to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude final product. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 97.9%, and the yield of step (2) was 89.4%.

[0048] Comparative Example 1 Step (1): Compared with Step (1) of Example 1, the only difference is that the non-aqueous solvent is replaced with a high-aqueous system consisting of 125 mL of ethanol and 125 mL of deionized water. After the reaction, the crude intermediate was obtained by the same post-treatment. The GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 88.7% as determined by gas chromatography.

[0049] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at position 6 was 95.8%, the selectivity of the 6-hydroxy group was 89.4%, and the retention rate of the chlorinated structure at position 8 was 87.6%. The results indicate that in a high-aqueous system, the side reactions of the substrate during electrolysis significantly increased, the selectivity of the 6-hydroxy target intermediate decreased, and the retention of the chlorinated structure at position 8 deteriorated. This demonstrates that the non-aqueous solvent used in this invention plays a crucial role in suppressing dechlorination side reactions.

[0050] Step (2): The reaction conditions were the same as in Step (2) of Example 1. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 96.1%, and the yield of Step (2) was 84.6%.

[0051] Comparative Example 2 Step (1): The only difference from Step (1) of Example 1 is that the supporting electrolyte is replaced with 12 g of sodium chloride. After the reaction, the crude intermediate is obtained by the same post-treatment. The GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 89.8% as determined by gas chromatography.

[0052] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at the 6-position was 91.9%, the selectivity of the 6-hydroxy group was 90.1%, and the retention rate of the chlorinated structure at the 8-position was 90.4%. The conductivity and interfacial stabilizing effect of ordinary inorganic salts in this non-aqueous system were insufficient, resulting in lower conversion rate, selectivity, and chlorinated structure retention rate than in Example 1.

[0053] Step (2): The reaction conditions were the same as in Step (2) of Example 1. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 96.7%, and the yield of Step (2) was 85.9%.

[0054] Comparative Example 3 Step (1): The only difference from step (1) of Example 1 is that the cathode current density is increased to 20 mA / cm². 2 The reaction was carried out for 1.5 h. After the reaction was completed, the crude intermediate was obtained through the same post-processing. Gas chromatography analysis showed that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 86.9%.

[0055] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at the 6-position was 98.2%, the selectivity of the 6-hydroxy group was 86.3%, and the retention rate of the chlorinated structure at the 8-position was 84.8%. Compared with Example 1, the results show that although excessively high current density can improve the conversion rate of the carbonyl group at the 6-position, it will aggravate the side reactions on the electrode surface and significantly reduce the retention rate of the chlorinated structure at the 8-position, indicating that the current density window has a specific selectivity.

[0056] Step (2): The reaction conditions were the same as in Step (2) of Example 1. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 95.4%, and the yield of Step (2) was 82.7%.

[0057] Comparative Example 4 Step (1): In a 500 mL reactor, add 50 g of ethyl 6-carbonyl-8-chlorooctanoate and 200 mL of ethanol, stir to form a homogeneous reaction system, and slowly add sodium borohydride under ice bath conditions to carry out the reduction reaction, controlling the temperature of the system to not rise too quickly during the addition process. After the addition is complete, continue the reaction until the raw materials are basically consumed. After the reaction is complete, slowly add an appropriate amount of water to quench, then extract with dichloromethane. The organic phase is washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure to obtain the crude intermediate. Gas chromatography analysis showed that the GC purity of ethyl 6-hydroxy-8-chlorooctanoate in the crude intermediate was 87.8%. The gas chromatogram is shown in the figure. Figure 3 .

[0058] Analysis of the intermediate obtained in step (1) showed that the conversion rate of the carbonyl group at position 6 was 93.6%, the selectivity of the 6-hydroxy group was 88.7%, and the retention rate of the chlorinated structure at position 8 was 89.1%. The results indicate that although traditional chemical reduction can achieve partial carbonyl group conversion, the reaction selectivity and the retention of the chlorinated structure at position 8 are not ideal, and the post-processing burden is heavy, which is not conducive to a smooth transition with the subsequent chlorination step.

[0059] Step (2): The reaction conditions were the same as in Step (2) of Example 1. Gas chromatography analysis showed that the GC purity of ethyl 6,8-dichlorooctanoate was 95.9%, and the yield of Step (2) was 84.1%. The gas chromatogram is shown below. Figure 4 .

[0060] Table 1 summarizes the experimental data of Examples 1-4 and Comparative Examples 1-4.

[0061] Table 1. Summary of experimental data from Examples 1-4 and Comparative Examples 1-4

[0062] As can be seen from Table 1, combined with the examples and comparative examples, the technical effect of the present invention does not stem from the conventional selection of a single condition, but rather from the synergistic control of a non-aqueous medium, a suitable supporting electrolyte, a specific cathode material, and a current density window. Compared with high-aqueous systems, unsuitable supporting electrolytes, excessively high current densities, and traditional chemical reduction, the present invention significantly improves the 6-hydroxyl selectivity and the 8-chlorination structure retention rate while maintaining a high 6-position carbonyl conversion rate, and enables subsequent photocatalytic chlorination steps to achieve higher purity and yield of ethyl 6,8-dichlorooctanoate.

[0063] The above are preferred embodiments of the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction, characterized in that, Includes the following steps: (1) ethyl 6-carbonyl-8-chlorooctanoate is mixed with a non-aqueous solvent and a supporting electrolyte, and cathodic reduction is carried out in a constant current mode to obtain ethyl 6-hydroxy-8-chlorooctanoate; the supporting electrolyte is tetrabutylammonium tetrafluoroborate, tetraethylammonium p-toluenesulfonate or lithium perchlorate, and the cathodic current density of the cathodic reduction is 3-15 mA / cm 2 ; (2) After dissolving the 6-hydroxy-8-chlorooctanoic acid ethyl ester in an organic solvent, a photocatalyst and a chlorine source are added, and then chlorination is carried out by visible light irradiation to obtain 6,8-dichlorooctanoic acid ethyl ester.

2. The method for preparing ethyl 6,8-dichlorooctanoate based on cathode selective reduction according to claim 1, characterized in that, The non-aqueous solvent is one or a combination of two or more of ethanol, isopropanol, and acetonitrile.

3. The method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction according to claim 1, characterized in that, The non-aqueous solvent is a non-aqueous mixed solvent obtained by mixing an alcohol solvent and acetonitrile, wherein the alcohol solvent is ethanol or isopropanol.

4. The method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction according to claim 1, characterized in that, The time of the cathode reduction is 1-5 h; the temperature of the cathode reduction is 20-50℃; the cathode current density is 5-10 mA / cm 2 .

5. The method for preparing ethyl 6,8-dichlorooctanoate based on cathode selective reduction according to claim 4, characterized in that, The cathode reduction time is 2-3 hours.

6. The method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction according to claim 1, characterized in that, The photocatalyst is Ru(bpy)3Cl2, and the chlorine source is N-chlorosuccinimide.

7. The method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction according to claim 1, characterized in that, The organic solvent is dichloromethane.

8. The method for preparing ethyl 6,8-dichlorooctanoate based on cathodic selective reduction according to claim 1, characterized in that, The visible light source is 395 nm.

9. The method for preparing ethyl 6,8-dichlorooctanoate based on cathode selective reduction according to claim 1, characterized in that, The supporting electrolyte is tetrabutylammonium tetrafluoroborate.

10. A method for preparing ethyl 6-hydroxy-8-chlorooctanoate, characterized in that, Includes the following steps: Ethyl 6-carbonyl-8-chlorooctanoate is mixed with a non-aqueous solvent and a supporting electrolyte, and cathodically reduced in a constant current mode to give ethyl 6-hydroxy-8-chlorooctanoate; the supporting electrolyte is tetrabutylammonium tetrafluoroborate, tetraethylammonium p-toluenesulfonate or lithium perchlorate, and the cathodic current density of the cathodic reduction is 3 to 15 mA / cm 2 .

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