Efficient catalytic synthesis method of chlorphenesin

Abstract

The invention relates to the technical field of organic synthesis, in particular to an efficient catalytic synthesis method of chlorphenesin, which comprises the following steps: dissolving ZIF-8 powder in absolute methanol for ultrasonic treatment, then adding ferric chloride ionic liquid for stirring and centrifuging, and then washing and drying solids obtained by centrifuging to obtain a ZIF-8 / ZIF-8 composite material; the composite catalyst is obtained; the preparation method comprises the following steps: adding parachlorophenol and a composite catalyst into isopropanol, mixing, heating and activating, then adding glycidol and a sodium hydroxide solution, carrying out heating reaction, filtering after the reaction is finished, and collecting filtrate; adding deionized water into the filtrate, stirring, standing for layering, discarding a lower-layer water phase to obtain an organic phase, carrying out reduced pressure distillation on the organic phase to recover isopropanol, and recrystallizing and drying a residual crude product to obtain chlorphenesin. The novel composite catalyst is adopted, and the product purity can reach 99% or above.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a high-efficiency catalytic synthesis method of chlorphenesin. Background Art

[0002] Chlorphenesin (3-(4-chlorophenoxy)-1,2-propylene glycol) is a preservative and antibacterial agent widely used in cosmetics and pharmaceuticals. Its synthesis method mainly uses p-chlorophenol and glycidol as raw materials and is prepared through a nucleophilic substitution reaction.

[0003] In the existing technology, this reaction usually uses a strong base such as sodium hydroxide as a catalyst, or adds a phase transfer catalyst (such as a quaternary ammonium salt) to improve the reaction efficiency. However, there are the following problems: 1. Traditional catalytic systems have low selectivity for nucleophilic substitution and are prone to generate byproducts such as diethers and epoxy ring-opening isomers, resulting in product purity that is difficult to exceed 99.0%. Multiple purifications are required, increasing process costs. 2. Existing catalysts (such as single metal salts and traditional molecular sieves) have difficulty simultaneously activating the nucleophilicity of the phenolic hydroxyl group of para-chlorophenol and regulating the ring-opening site of glycidol, resulting in insufficient reaction selectivity. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides a high-efficiency catalytic synthesis method of chlorphenesin. The present invention adopts a new composite catalyst to selectively activate the phenolic hydroxyl group of p-chlorophenol through the pore confinement effect of ZIF-8, combined with the Fe in the ferric chloride ionic liquid. 3+ The directional coordination effect on glycidol guides the nucleophilic substitution reaction to proceed in a directional manner, which can make the product purity reach more than 99%.

[0005] To this end, the present invention provides the following technical solutions: In a first aspect, the present invention provides a method for efficiently catalyzing the synthesis of chlorphenesin in an optional embodiment, comprising the following steps: S1: ZIF-8 powder is dissolved in anhydrous methanol and subjected to ultrasonic treatment. Then, ferric chloride ionic liquid is added, stirred, and centrifuged. The solid obtained by centrifugation is then washed and dried to obtain a composite catalyst. S2: adding p-chlorophenol and the composite catalyst to isopropyl alcohol, mixing and heating to activate, then adding glycidol and sodium hydroxide solution to carry out temperature reaction, filtering after the reaction is completed, and collecting the filtrate; S3: Deionized water is added to the filtrate, and the mixture is allowed to stand for stratification after stirring. The lower aqueous phase is discarded to obtain an organic phase, and the organic phase is subjected to reduced pressure distillation to recover isopropyl alcohol. The remaining crude product is recrystallized and dried to obtain chlorphenesin.

[0006] In the present invention, the nanopores of ZIF-8 powder can selectively accommodate p-chlorophenol molecules and form hydrogen bonds with the phenolic hydroxyl group through the nitrogen atom on the imidazole ring, thereby enhancing its nucleophilic activity and repelling larger by-product precursors. 3+ Coordinating with the oxygen atom in glycidol, the electron-induced effect imparts a partial positive charge to the β-carbon of the epoxy ring, directing the nucleophile to attack this site, increasing the ring-opening selectivity to over 99%. ZIF-8 and the ferric chloride ionic liquid bind electrostatically, forming a synergistic system of "intra-pore activated nucleophile + pore-orifice directed catalytic substrate," which inhibits side reactions both spatially and electronically.

[0007] Preferably, the preparation method of the ZIF-8 powder is: adding zinc nitrate and 2-methylimidazole to N,N-dimethylformamide for stirring reaction, centrifuging after the reaction is completed, collecting the precipitate, washing, drying and crushing the precipitate to obtain ZIF-8 powder.

[0008] The volume mass ratio of the N,N-dimethylformamide, zinc nitrate and 2-methylimidazole is 100mL:2-2.5g:2.5-3g; and / or the temperature of the stirring reaction is 55-65°C, the time is 20-28h, and the rotation speed is 250-350rpm; and / or the speed of the centrifugation is 7000-9000rpm, and the time is 5-15min; and / or the solution used for washing is N,N-dimethylformamide and methanol, and the number of times the precipitate is washed with N,N-dimethylformamide and methanol is 3 times respectively; and / or the temperature of the drying is 50-70°C, and the time is 10-14h.

[0009] Preferably, the preparation method of the ferric chloride ionic liquid is: after adding 1-methyl-3-butylimidazolium chloride and ferric chloride to anhydrous methanol, stirring and reacting under a protective gas atmosphere, after the reaction is completed, vacuum distillation is performed to remove methanol, and the residual product after the vacuum distillation is washed and dried to obtain the ferric chloride ionic liquid.

[0010] The volume mass ratio of the anhydrous methanol, 1-methyl-3-butylimidazolium chloride and ferric chloride is 100 mL: 18-20 g: 26-28 g; and / or the stirring reaction temperature is 35-45° C. and the time is 5-7 h; and / or the pressure of the reduced pressure distillation is -0.09 MPa and the temperature is 40° C.; and / or the solution used for washing is ethyl acetate, and the number of washings is 3 times; the drying temperature is 50-70° C. and the time is 6-10 h.

[0011] Preferably, in step S1, the volume mass ratio of the anhydrous methanol, ZIF-8 and ferric chloride ionic liquid is 100 mL: 4-6 g: 8-12 g; and / or the ultrasonic treatment time is 25-35 min, the power is 250-350 W; and / or the stirring temperature is 25-35 ° C, the time is 10-14 h; and / or the washing solution is anhydrous methanol, the number of washing times is 3 times; and / or the drying temperature is 55-65 ° C, and the time is 8-12 h.

[0012] Preferably, in step S2, the mass-to-volume ratio of p-chlorophenol, glycidol, and sodium hydroxide solution is 1 g:(0.8-1.2) g:(3.5-5.5) mL; and / or the mass fraction of the sodium hydroxide solution is 15%; and / or the temperature of the activation is 50-55°C, and the duration is 20-40 minutes. The amount of the composite catalyst added is 2-5% of the mass of p-chlorophenol; and / or the volume-to-mass ratio of isopropyl alcohol to p-chlorophenol is 4-5 mL:1 g; and / or the temperature of the reaction is 60-70°C, and the duration is 2-4 hours.

[0013] Preferably, in step S3, the volume ratio of deionized water to isopropanol is 1:2-3; and / or the stirring time is 20-40 minutes; and / or the pressure of the reduced pressure distillation is -0.08 MPa and the temperature is 40°C. The solution used for the recrystallization is a cyclohexane-ethanol mixed solution, the volume ratio of cyclohexane to ethanol is 2-4:1, and the volume ratio of the cyclohexane-ethanol mixed solution to isopropanol is 0.8-1.2:1; and / or the recrystallization method is: dissolving the remaining crude product in the cyclohexane-ethanol mixed solution at 70-90°C, cooling to 0°C, and then standing for 3-5 hours; and / or the drying temperature is 40-60°C, the time is 4-8 hours, and the pressure is -0.09 MPa.

[0014] Compared with the prior art, the present invention has one of the following beneficial effects: 1. The present invention adopts a new composite catalyst to selectively activate the phenolic hydroxyl group of p-chlorophenol through the pore confinement effect of ZIF-8, combined with Fe 3+ The directional coordination effect on glycidol guides the nucleophilic substitution reaction to proceed in a directional manner, which can make the product purity reach more than 99%. DETAILED DESCRIPTION

[0015] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0016] In the following examples and comparative examples, zinc nitrate (analytical grade), 2-methylimidazole (analytical grade), N,N-dimethylformamide (DMF, anhydrous grade), 1-methyl-3-butylimidazole chloride (purity ≥99%), ferric chloride (analytical grade), and methanol (anhydrous grade).

[0017] The technical solution of the present invention will be described below with reference to the embodiments.

[0018] Example 1 The present embodiment provides a kind of efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0019] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0020] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 30℃ for 12h. Then, the solid is collected by centrifugation. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0021] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 3 g of the composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of propylene oxide and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0022] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0023] Example 2 The present embodiment provides a kind of efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0024] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0025] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 30℃ for 12h. Then, the solid is collected by centrifugation. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0026] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 2 g of the composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of propylene oxide and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0027] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0028] Example 3 The present embodiment provides a kind of efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0029] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0030] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 30℃ for 12h. Then, the solid is collected by centrifugation. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0031] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 4 g of a composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of propylene oxide and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0032] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0033] Example 4 The present embodiment provides a kind of efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0034] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0035] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 30℃ for 12h. Then, the solid is collected by centrifugation. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0036] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 5 g of a composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of glycidol and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0037] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0038] Comparative Example 1 This comparative example provides a highly efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 100 g of p-chlorophenol and 450 mL of isopropanol to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then, add 100 g of glycidol and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%). Then, heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0039] S2: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of cyclohexane-ethanol mixed solvent (cyclohexane and ethanol volume ratio 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0040] Comparative Example 2 This comparative example provides a highly efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0041] S2: Add 100 g of p-chlorophenol, 450 mL of isopropanol, and 3 g of ZIF-8 powder to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then, add 100 g of glycidol and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0042] S3: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0043] Comparative Example 3 This comparative example provides a highly efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection and stir to react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0044] S2: Add 100 g of p-chlorophenol, 450 mL of isopropanol, and 3 g of ferric chloride ionic liquid to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then, add 100 g of glycidol and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0045] S3: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0046] Comparative Example 4 This comparative example provides a highly efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0047] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0048] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 40℃ for 12h. Then, the solid is collected by centrifugation. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0049] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 3 g of the composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of propylene oxide and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0050] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0051] Comparative Example 5 This comparative example provides a highly efficient catalytic synthesis method of chlorphenesin, comprising the following steps: S1: Add 200 mL of N,N-dimethylformamide to a 500 mL three-necked flask, add 4.38 g of zinc nitrate while stirring, add 5.76 g of 2-methylimidazole after dissolution, raise the temperature to 60°C, and stir at constant temperature for 24 hours (speed of 300 rpm). After the reaction is completed, centrifuge at 8000 rpm for 10 minutes, collect the precipitate, wash the precipitate with N,N-dimethylformamide three times (50 mL each time), and then wash the precipitate with methanol three times (50 mL each time), and finally dry it in vacuum at 60°C for 12 hours, crush it into powder, and obtain ZIF-8 powder.

[0052] S2: Add 100 mL of anhydrous methanol to a 250 mL round-bottom flask, add 19.1 g of 1-methyl-3-butylimidazolium chloride, stir to dissolve, then add 27.0 g of ferric chloride. Heat to 40°C under nitrogen protection, stir and react for 6 h. After the reaction, perform vacuum distillation at 40°C (pressure of -0.09 MPa) to remove methanol. Wash the remaining product after vacuum distillation with ethyl acetate three times (50 mL each time), and finally dry in vacuo at 60°C for 8 h to obtain ferric chloride ionic liquid.

[0053] S3: Take 5g of ZIF-8 powder and disperse it in 100mL of anhydrous methanol. Ultrasonic treatment is carried out for 30min (power is 300W) to form a suspension. 10g of ferric chloride ionic liquid is slowly added dropwise. Stir at 20℃ for 12h, then centrifuge to collect the solid. The solid obtained by centrifugation is washed three times with anhydrous methanol and finally dried in vacuum at 60℃ for 10h to obtain a composite catalyst.

[0054] S4: Add 100 g of p-chlorophenol, 450 mL of isopropanol and 3 g of the composite catalyst to a four-necked flask. After nitrogen replacement three times, heat to 55°C and stir to activate for 30 min. Then add 100 g of propylene oxide and 450 mL of sodium hydroxide solution (the mass fraction of sodium hydroxide is 15%), then heat to 65°C and react for 3 h. After the reaction is completed, filter and recover the catalyst to obtain a filtrate.

[0055] S5: Add 250 mL of deionized water to the filtrate, stir for 30 min, let stand to separate the layers, and discard the lower aqueous phase; distill the organic phase under reduced pressure to recover isopropanol, and recrystallize the remaining crude product twice with 450 mL of a cyclohexane-ethanol mixed solvent (cyclohexane and ethanol in a volume ratio of 3:1) (dissolve at 80°C each time and let stand at 0°C for 4 h); the crystalline product is vacuum dried (50°C, -0.09 MPa, 6 h) to obtain chlorphenesin.

[0056] Experimental example The purity of chlorphenesin was determined by high performance liquid chromatography (HPLC). The specific parameters were as follows: Instrument: High performance liquid chromatography (equipped with UV detector); Chromatographic column: C18 reverse phase column (250 mm × 4.6 mm, 5 μm); Mobile phase: methanol-water mixed solution (volume ratio 60:40); Flow rate: 1.0 mL / min; Detection wavelength: 280nm; Column temperature: 30°C; Injection volume: 10 μL; Using the area normalization method, the percentage of the main peak area of ​​chlorphenesin to the total peak area is the product purity. The test results are shown in Table 1.

[0057] Table 1 Chlorphenesin test results of Examples 1-4 and Comparative Examples 1-5 purity(%) Example 1 99.6 Example 2 99.2 Example 3 99.7 Example 4 99.5 Comparative Example 1 96.8 Comparative Example 2 97.5 Comparative Example 3 98.0 Comparative Example 4 98.8 Comparative Example 5 98.5 It can be seen from Table 1 that the purity of chlorphenesin prepared in Examples 1-4 is all above 99%, indicating that the use of the new composite catalyst of the present invention can make the product purity reach more than 99%. The purity of Comparative Example 1 is only 96.8, which is 2.8% lower than that of Example 1. It can be seen that the purity of the product prepared without using the new composite catalyst of the present invention and only under the catalysis of sodium hydroxide is poor. The purity of Example 1 is significantly higher than that of Comparative Examples 2 and 3, which proves that the composite of ZIF-8 powder and ferric chloride ionic liquid can reduce by-products through the synergistic effect of pore confinement and directional catalysis, thereby improving the purity of the product. The purity of Comparative Examples 4 and 5 is lower than that of Example 1, indicating that 30°C is the optimal temperature for the composite catalyst to form a stable structure. Too high or too low a temperature will lead to uneven loading of the ionic liquid and reduce the catalytic selectivity.

[0058] Although the principles of the present invention have been described in detail above in conjunction with the preferred embodiments of the present invention, those skilled in the art should understand that the above embodiments are merely illustrative of the present invention and are not intended to limit the scope of the present invention. The details in the embodiments do not constitute a limitation on the scope of the present invention. Without departing from the spirit and scope of the present invention, any obvious changes such as equivalent transformations and simple substitutions based on the technical solution of the present invention fall within the scope of protection of the present invention.

Claims

1. A high-efficiency catalytic synthesis method of chlorphenesin, characterized in that, The following steps are involved: S1: ZIF-8 powder is dissolved in anhydrous methanol and subjected to ultrasonic treatment. Then, ferric chloride ionic liquid is added, stirred, and centrifuged. The solid obtained by centrifugation is then washed and dried to obtain a composite catalyst. S2: adding p-chlorophenol and the composite catalyst to isopropyl alcohol, mixing and heating to activate, then adding glycidol and sodium hydroxide solution to carry out temperature reaction, filtering after the reaction is completed, and collecting the filtrate; S3: Deionized water is added to the filtrate, and the mixture is allowed to stand for stratification after stirring. The lower aqueous phase is discarded to obtain an organic phase, and the organic phase is subjected to reduced pressure distillation to recover isopropyl alcohol. The remaining crude product is recrystallized and dried to obtain chlorphenesin.

2. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, The preparation method of the ZIF-8 powder is: Zinc nitrate and 2-methylimidazole were added to N,N-dimethylformamide for stirring reaction. After the reaction was completed, the mixture was centrifuged, and the precipitate was collected. The precipitate was washed, dried and crushed to obtain ZIF-8 powder.

3. the efficient catalytic synthesis method of chlorphenesin according to claim 2, is characterized in that, The volume mass ratio of the N,N-dimethylformamide, zinc nitrate and 2-methylimidazole is 100 mL: 2-2.5 g: 2.5-3 g; and / or, The stirring reaction is carried out at a temperature of 55-65°C, a time of 20-28 hours, and a rotation speed of 250-350 rpm; and / or, The centrifugal speed is 7000-9000 rpm and the time is 5-15 min; and / or, The washing solution is N, N-dimethylformamide and methanol, and the number of times the precipitate is washed with N, N-dimethylformamide and methanol is 3 times respectively; and / or, The drying temperature is 50-70° C. and the drying time is 10-14 hours.

4. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, The preparation method of the ferric chloride ionic liquid comprises the following steps: adding 1-methyl-3-butylimidazolium chloride and ferric chloride to anhydrous methanol, stirring the mixture for reaction under a protective gas atmosphere, performing reduced pressure distillation after the reaction to remove the methanol, and washing and drying the residual product after the reduced pressure distillation to obtain the ferric chloride ionic liquid.

5. the efficient catalytic synthesis method of chlorphenesin according to claim 4, is characterized in that, The volume mass ratio of anhydrous methanol, 1-methyl-3-butylimidazolium chloride and ferric chloride is 100 mL: 18-20 g: 26-28 g; and / or, The stirring reaction temperature is 35-45°C and the time is 5-7h; and / or, The pressure of the reduced pressure distillation is -0.09 MPa and the temperature is 40° C.; and / or, The washing solution used was ethyl acetate, and the number of washings was 3 times; The drying temperature is 50-70° C. and the drying time is 6-10 hours.

6. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, In step S1, the volume mass ratio of anhydrous methanol, ZIF-8 and ferric chloride ionic liquid is 100 mL: 4-6 g: 8-12 g; and / or, The ultrasonic treatment time is 25-35 minutes and the power is 250-350W; and / or, The stirring temperature is 25-35°C and the stirring time is 10-14h; and / or, The washing solution is anhydrous methanol, and the number of washing times is 3 times; and / or, The drying temperature is 55-65° C. and the drying time is 8-12 hours.

7. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, In step S2, the mass volume ratio of the p-chlorophenol, glycidol and sodium hydroxide solution is 1 g: (0.8-1.2) g: (3.5-5.5) mL; and / or, The mass fraction of the sodium hydroxide solution is 15%; and / or, The temperature of the temperature-raising activation is 50-55° C., and the time is 20-40 minutes.

8. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, In step S2, the amount of the composite catalyst added is 2-5% of the mass of p-chlorophenol; and / or, The volume mass ratio of isopropyl alcohol to p-chlorophenol is 4-5 mL:1 g; and / or, The temperature of the temperature-raising reaction is 60-70° C. and the time is 2-4 hours.

9. the efficient catalytic synthesis method of chlorphenesin according to claim 1, is characterized in that, In step S3, the volume ratio of deionized water to isopropyl alcohol is 1:2-3; and / or, The stirring time is 20-40 min; and / or, The pressure of the reduced pressure distillation is -0.08 MPa and the temperature is 40°C.

10. The efficient catalytic synthesis method of chlorphenesin according to claim 1, wherein In step S3, the solution used for the recrystallization is a cyclohexane-ethanol mixed solution, the volume ratio of the cyclohexane to the ethanol is 2-4:1, and the volume ratio of the cyclohexane-ethanol mixed solution to isopropanol is 0.8-1.2:1; and / or, The recrystallization method is: dissolving the remaining crude product in a cyclohexane-ethanol mixed solution at 70-90° C., cooling to 0° C. and then standing for 3-5 hours; and / or, The drying temperature is 40-60° C., the drying time is 4-8 hours, and the pressure is -0.09 MPa.