Preparation method of 2-cyclopentenone

Abstract

The invention discloses a preparation method of 2-cyclopentenone, which comprises the following steps: taking cyclopentanone (compound V) as an initial raw material, and carrying out bromination reaction to obtain 2-bromocyclopentanone (compound IV); then carrying out carbonyl protection to obtain 2-bromo-1, 1-dimethoxy cyclopentane (a compound III); then carrying out elimination reaction to obtain 3, 3-dimethoxy cyclopent-1-ene (a compound II); according to the method, the total yield can reach 75.46%, the raw materials are cheap and easy to obtain, the use of dangerous reagents is avoided, the post-treatment is mild and efficient, and the method is suitable for industrial large-scale production.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical synthesis, in particular to a preparation method of 2-cyclopentenone. BACKGROUND

[0002] 2-cyclopentenone is an important pharmaceutical intermediate. US20040138505A1 discloses a preparation method of 2-bromocyclopentanone, which uses cyclopentanone as a starting material and liquid bromine as a bromination reagent to obtain 2-bromocyclopentanone, and then uses lithium carbonate and lithium bromide monohydrate as a base to further convert the 2-bromocyclopentanone into a DMF solution of 2-cyclopentenone at 100 DEG C in DMF solvent. However, the patent only obtains a DMF solution of 2-cyclopentenone, and no subsequent purification is reported. In the preparation of alpha-bromoketone, using liquid bromine as a bromination reagent produces a large amount of dibromosubstituted product by-product, which reduces the purity of the product and complicates the post-treatment. In addition, the boiling point of 2-cyclopentenone is similar to that of the solvent DMF, and 2-cyclopentenone is very water-soluble, and cannot be removed by water washing, so it is difficult to completely separate DMF from 2-cyclopentenone, and it is difficult to obtain pure 2-cyclopentenone. SUMMARY

[0003] The present application aims to overcome the deficiencies of the prior art, and provides a preparation method of 2-cyclopentenone.

[0004] To achieve the above-mentioned purpose, the technical solutions provided by the present application are as follows: In one aspect, the present application provides a preparation method of 2-cyclopentenone, comprising: , The bromination reagent is N-bromosuccinimide or dibromohydantoin; the acidic catalyst is p-toluenesulfonic acid; and the basic reagent is sodium methoxide or sodium ethoxide.

[0005] In some embodiments, in the preparation of compound II from compound III, the reaction organic solvent is methanol or ethanol, and the reaction temperature is 64-78 DEG C.

[0006] In some embodiments, in the preparation of compound II from compound III, the molar ratio of compound III to the basic reagent is in the range of 1:1.1-1.2.

[0007] In some embodiments, in the preparation of compound II from compound III, the post-treatment step of the reaction is: after the reaction solution is cooled, ammonium chloride is added dropwise to quench the reaction, petroleum ether is used for extraction, drying, and vacuum concentration to obtain compound II.

[0008] In some embodiments, in the preparation of compound I from compound II, the reaction mixed solvent is tetrahydrofuran and water.

[0009] In some embodiments, in the preparation of compound I from compound II, the reaction temperature is 20-30℃.

[0010] In some embodiments, in the preparation of compound I from compound II, the post-treatment step of the reaction is: adjusting the pH value to be greater than 7 with sodium carbonate, distilling the reaction solvent under reduced pressure, extracting with dichloromethane, drying, and concentrating under reduced pressure to obtain compound I.

[0011] In some embodiments, in the preparation of compound IV from compound V, when the bromination reagent is dibromohydantoin, the molar ratio of compound V:dibromohydantoin is in the range of 1:0.55-0.6; when the bromination reagent is N-bromosuccinimide, the molar ratio of compound V:N-bromosuccinimide is in the range of 1:1.1-1.2.

[0012] In some embodiments, in the preparation of compound IV from compound V, the organic solvent of the reaction is methyl tert-butyl ether or dichloromethane.

[0013] In some embodiments, in the preparation of compound IV from compound V, the reaction temperature is 20-30℃.

[0014] Beneficial effects: The present application takes cyclopentanone (compound V) as the starting material, first obtains 2-bromocyclopentanone (compound IV) through bromination reaction; then obtains 2-bromo-1,1-dimethoxycyclopentane (compound III) through carbonyl protection; then obtains 3,3-dimethoxycyclopent-1-ene (compound II) through elimination reaction; and finally obtains 2-cyclopentenone (compound I) through deprotection reaction, and the total yield can reach 75.46%. The route has low-cost and readily available raw materials, avoids the use of dangerous reagent liquid bromine, and has mild and efficient post-treatment, and has great potential for large-scale production and economic value.

[0015] The abbreviations of the reaction reagents involved in the specification are as follows: DMF: N,N-dimethylformamide; p -TsOH: p-toluenesulfonic acid; NaOMe: sodium methoxide; MeOH: methanol; THF: tetrahydrofuran. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 The gas phase spectrum of the product 2-cyclopentenone is shown. DETAILED DESCRIPTION

[0017] Example 1:

[0018] Preparation of compound IV: In a four-necked flask, add methyl tert-butyl ether, open the mechanical stirring, then add dibromohydantoin (314.5 g, 1.1 mol, 0.55 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq), and protect the reaction solution with nitrogen, and cool in an ice water bath. When the internal temperature is 5 ℃, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) dropwise with a constant pressure dropping funnel. It takes about 1 h to drop, and the reaction solution is slowly warmed to 25 ℃. Stir the reaction at 25 ℃ for 2 h. After the reaction is completed, filter, and wash the filter cake with 200 mL of methyl tert-butyl ether once. Pour the methyl tert-butyl ether phase into a separatory funnel, wash with 500 mL of saturated sodium bicarbonate aqueous solution once, and wash with 300 mL of water once. Dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and remove the methyl tert-butyl ether by distillation under reduced pressure to obtain a brownish yellow liquid 295.6 g. Distill the crude product under reduced pressure with an oil pump to obtain a brown liquid (compound IV) 278.3 g, with a yield of 85.38% and a GC purity of 98.5%.

[0019] Preparation of compound III: In a four-necked flask, add methyl tert-butyl ether, open the mechanical stirring, then add dibromohydantoin (314.5 g, 1.1 mol, 0.55 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq), and protect the reaction solution with nitrogen, and cool in an ice water bath. When the internal temperature is 5 ℃, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) dropwise with a constant pressure dropping funnel. It takes about 1 h to drop, and the reaction solution is slowly warmed to 25 ℃. Stir the reaction at 25 ℃ for 2 h. After the reaction is completed, filter, and wash the filter cake with 200 mL of methyl tert-butyl ether once. Pour the methyl tert-butyl ether phase into a separatory funnel, wash with 500 mL of saturated sodium bicarbonate aqueous solution once, and wash with 300 mL of water once. Dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and remove the methyl tert-butyl ether by distillation under reduced pressure to obtain a brownish yellow liquid 295.6 g. Distill the crude product under reduced pressure with an oil pump to obtain a brown liquid (compound IV) 278.3 g, with a yield of 85.38% and a GC purity of 98.5%.

[0020] Preparation of compound II: Compound III (210 g, 1.0 mol, 1.0 eq) was dissolved in methanol, and the reaction solution was cooled to an internal temperature of 10-15 °C with an ice water bath. Then sodium methoxide solid (65.1 g, 1.2 mol, 1.2 eq) was added in batches, about 2 g at a time, and the addition was completed in about 0.5 h, at which time the internal temperature was 14 °C. Then the ice water bath was removed, and the reaction solution was heated with an oil bath, with reflux at an internal temperature of 64 °C. The reflux was maintained for 4 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 500 mL of saturated ammonium chloride solution was added dropwise to the reaction solution, and stirred for 10 min. Then the reaction solution was transferred to a separatory funnel, and extracted with 1 L of petroleum ether once. The aqueous phase was extracted with 1 L of petroleum ether once after separation. The petroleum ether phases were combined and extracted with 300 mL of water once. The petroleum ether phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 121 g of a light yellow liquid (compound II), with a yield of 94.53% and a GC purity of 98.2%.

[0021] Preparation of compound I: Tetrahydrofuran and water were added to a four-necked flask in sequence, and stirring was started. Then compound II (128 g, 1.0 mol, 1.0 eq) was added in one portion, and p-toluenesulfonic acid (8.6 g, 0.05 mol, 0.05 eq) was added at an internal temperature of 25 °C. The reaction was continued to stir for 2 h. After the reaction was completed, 10 g of sodium carbonate solid was added to the reaction solution, and stirred for 20 min. The pH was measured to be >7. The reaction solution was distilled under reduced pressure to distill most of the tetrahydrofuran. Then the crude product was poured into a separatory funnel, and 200 mL of water and 600 mL of dichloromethane were added. The aqueous phase was extracted with 400 mL of dichloromethane once after extraction. The dichloromethane phases were combined and washed with 100 mL of saturated NaCl solution once. The dichloromethane phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 78.6 g of a colorless transparent liquid (compound I), with a yield of 95.85% and a GC purity of 98.75%.

[0022] Example 2:

[0023] Preparation of compound IV: In a four-necked flask, dichloromethane was added, mechanical stirring was started, and then dibromohydantoin (343 g, 1.2 mol, 0.6 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq) were added in batches. The reaction solution was protected by nitrogen, and was cooled in an ice-water bath. When the internal temperature was 5 ℃, cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) was added dropwise using a constant-pressure dropping funnel. The dropwise addition was completed in about 1 h, and the reaction solution was slowly warmed to 20 ℃. The internal temperature was 20 ℃, and the reaction was stirred for 2 h. After the reaction was completed, the filter cake was washed once with 200 mL of dichloromethane. The dichloromethane phase was poured into a separatory funnel, washed once with 500 mL of saturated aqueous sodium bicarbonate solution, and washed once with 300 mL of water. The dichloromethane phase was dried over anhydrous sodium sulfate, and dichloromethane was removed by distillation under reduced pressure to obtain a brownish yellow liquid 365.6 g. The crude product was distilled under reduced pressure using an oil pump to obtain a brown liquid (compound IV) 305.6 g, with a yield of 93.75% and a GC purity of 98.55%.

[0024] Preparation of compound III: In a four-necked flask, dichloromethane was added, mechanical stirring was started, and then compound IV (244.5 g, 1.5 mol, 1.0 eq) was added in one portion, followed by the addition of p-toluenesulfonic acid (25.8 g, 0.15 mol, 0.1 eq). When the internal temperature was 25 ℃, trimethyl orthoformate (175.1 g, 1.65 mol, 1.1 eq) was added dropwise into the reaction solution using a constant-pressure dropping funnel, and the dropwise addition was completed in about 2 h while the internal temperature was controlled to be no more than 30 ℃. The reaction was continuously stirred for 6 h, and then 500 mL of saturated sodium carbonate solution was added dropwise into the reaction solution, and stirred for 10 min. The reaction solution was transferred into a separatory funnel, and after separation, the dichloromethane phase was washed once with 300 mL of water. The dichloromethane phase was dried over anhydrous sodium sulfate, and then dichloromethane was removed by distillation under reduced pressure to obtain a light yellow liquid (compound III 298.3 g, with a yield of 95.12%). The crude compound III was directly used in the next step reaction.

[0025] Preparation of compound II: Compound III (252 g, 1.2 mol, 1.0 eq) was dissolved in ethanol, and the reaction solution was cooled to an internal temperature of 10-15 °C with an ice water bath. Then sodium ethoxide solid (77.8 g, 1.44 mol, 1.2 eq) was added in batches, about 2 g at a time, and the addition was completed in about 1 h, at which time the internal temperature was 14 °C. Then the ice water bath was removed, and the reaction solution was heated with an oil bath, with reflux at an internal temperature of 78 °C. The reflux was maintained for 4 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 500 mL of saturated ammonium chloride solution was added dropwise to the reaction solution, and stirred for 10 min. Then the reaction solution was transferred to a separatory funnel, and extracted with 1 L of petroleum ether once. The aqueous phase was extracted with 1 L of petroleum ether once after separation. The petroleum ether phases were combined and extracted with 300 mL of water once. The petroleum ether phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 144.7 g of a light yellow liquid (Compound II), with a yield of 93.67% and a GC purity of 98.35%.

[0026] Preparation of Compound I: Tetrahydrofuran and water were added to a four-necked flask in sequence, and stirring was started. Then Compound II (128 g, 1.0 mol, 1.0 eq) was added in one portion, and p-toluenesulfonic acid (8.6 g, 0.05 mol, 0.05 eq) was added at an internal temperature of 25 °C. The reaction was continued to stir for 2 h. After the reaction was completed, 10 g of sodium carbonate solid was added to the reaction solution, and stirred for 20 min. The pH was measured to be >7. The reaction solution was distilled under reduced pressure to distill off most of the tetrahydrofuran. Then the crude product was poured into a separatory funnel, and 200 mL of water and 600 mL of dichloromethane were added. The aqueous phase was extracted with 400 mL of dichloromethane once after extraction. The dichloromethane phases were combined and washed with 100 mL of saturated NaCl solution once. The dichloromethane phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 79.2 g of a colorless transparent liquid (Compound I), with a yield of 96.59% and a GC purity of 98.23%.

[0027] Example 3:

[0028] Preparation of Compound IV: In a four-necked flask, add methyl tert-butyl ether, and add N-bromosuccinimide (391.5 g, 2.2 mol, 1.1 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq) in batches under mechanical stirring, and protect the reaction solution with nitrogen, and cool in an ice water bath. When the internal temperature is 5 ℃, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) dropwise with a constant pressure dropping funnel, and drop for about 1 h, and slowly warm the reaction solution to 25 ℃. Continue to stir the reaction at an internal temperature of 25 ℃ for 2 h. After the reaction is completed, filter, and wash the filter cake with 200 mL of methyl tert-butyl ether once. Then wash the methyl tert-butyl ether phase with 500 mL of saturated sodium bicarbonate aqueous solution once, and wash with 300 mL of water once. Dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and then remove the methyl tert-butyl ether by distillation under reduced pressure to obtain 357.2 g of a brownish yellow liquid. Distill the crude product under reduced pressure with an oil pump to obtain 304.1 g of a brown liquid (compound IV), with a yield of 93.29% and a GC purity of 98.26%.

[0029] Preparation of compound III: In a four-necked flask, add methyl tert-butyl ether, and add N-bromosuccinimide (391.5 g, 2.2 mol, 1.1 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq) in batches under mechanical stirring, and protect the reaction solution with nitrogen, and cool in an ice water bath. When the internal temperature is 5 ℃, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) dropwise with a constant pressure dropping funnel, and drop for about 1 h, and slowly warm the reaction solution to 25 ℃. Continue to stir the reaction at an internal temperature of 25 ℃ for 2 h. After the reaction is completed, filter, and wash the filter cake with 200 mL of methyl tert-butyl ether once. Then wash the methyl tert-butyl ether phase with 500 mL of saturated sodium bicarbonate aqueous solution once, and wash with 300 mL of water once. Dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and then remove the methyl tert-butyl ether by distillation under reduced pressure to obtain 357.2 g of a brownish yellow liquid. Distill the crude product under reduced pressure with an oil pump to obtain 304.1 g of a brown liquid (compound IV), with a yield of 93.29% and a GC purity of 98.26%.

[0030] Preparation of compound II: Compound III (210 g, 1.0 mol, 1.0 eq) was dissolved in methanol, and the reaction solution was cooled to an internal temperature of 10-15 °C with an ice water bath. Then sodium methoxide (64.8 g, 1.2 mol, 1.2 eq) was added in batches, about 2 g at a time, and the addition was completed in about 0.5 h, at which time the internal temperature was 14 °C. Then the ice water bath was removed, and the reaction solution was heated with an oil bath, with reflux at an internal temperature of 70 °C. The reflux was maintained for 4 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 500 mL of saturated ammonium chloride solution was added dropwise to the reaction solution, and stirred for 10 min. Then the reaction solution was transferred to a separatory funnel, and extracted with 1 L of petroleum ether once. The aqueous phase was extracted with 1 L of petroleum ether once after separation. The petroleum ether phases were combined and extracted with 300 mL of water once. The petroleum ether phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 121.5 g of a light yellow liquid (Compound II), with a yield of 94.38% and a GC purity of 98.86%.

[0031] Preparation of Compound I: Tetrahydrofuran and water were sequentially added to a four-necked flask, and stirring was started. Then Compound II (256 g, 2.0 mol, 1.0 eq) was added in one portion, and p-toluenesulfonic acid (19.2 g, 0.1 mol, 0.05 eq) was added at an internal temperature of 30 °C. The stirring was continued for 2 h. After the reaction was completed, 30 g of sodium carbonate was added to the reaction solution, and stirred for 20 min. The pH was measured to be >7. The reaction solution was distilled under reduced pressure to remove most of the tetrahydrofuran. Then the crude product was poured into a separatory funnel, and 400 mL of water and 1600 mL of dichloromethane were added. The aqueous phase was extracted with 1000 mL of dichloromethane once. The dichloromethane phases were combined and washed with 500 mL of saturated NaCl solution once. The dichloromethane phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 158.1 g of a colorless transparent liquid (Compound I), with a yield of 96.41% and a GC purity of 98.46%.

[0032] Example 4:

[0033] Preparation of Compound IV: In a four-necked flask, add dichloromethane, and add N-bromosuccinimide (427.1 g, 2.4 mol, 1.2 eq), p-toluenesulfonic acid (17.2 g, 0.1 mol, 0.05 eq) in batches under mechanical stirring, and protect the reaction solution with nitrogen, and cool in an ice water bath. When the internal temperature is 5 ℃, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) dropwise with a constant pressure dropping funnel, and drop for about 1 h, and slowly warm the reaction solution to 30 ℃. Continue to stir the reaction at an internal temperature of 30 ℃ for 2 h. After the reaction is completed, filter, and wash the filter cake with 200 mL of dichloromethane once. Then wash the dichloromethane phase with 500 mL of saturated aqueous sodium bicarbonate solution once, and wash with 300 mL of water once. Dry the dichloromethane phase with anhydrous sodium sulfate, and then remove the dichloromethane by distillation under reduced pressure to obtain 362.2 g of a brownish yellow liquid. Distill the crude product under reduced pressure with an oil pump to obtain 301.8 g of a brown liquid (compound IV), with a yield of 92.59% and a GC purity of 98.24%.

[0034] Preparation of compound III: In a four-necked flask, add dichloromethane, and add compound IV (195.6 g, 1.2 mol, 1.0 eq) in one portion under mechanical stirring, and then add p-toluenesulfonic acid (20.7 g, 0.12 mol, 0.1 eq). When the internal temperature is 25 ℃, add trimethyl orthoformate (140.0 g, 1.32 mol, 1.1 eq) dropwise into the reaction solution with a constant pressure dropping funnel, and control the dropping speed, and drop for about 2 h, and keep the internal temperature below 30 ℃. Continue to stir the reaction for 6 h, and then add 500 mL of saturated sodium carbonate solution to the reaction solution, and stir for 10 min. Transfer the reaction solution to a separatory funnel, and separate the dichloromethane phase, and wash with 300 mL of water once, and dry the dichloromethane phase with anhydrous sodium sulfate, and then remove the dichloromethane by distillation under reduced pressure to obtain 233.6 g of a light yellow liquid (compound III), with a yield of 93.11%. The crude compound III is directly used in the next step reaction.

[0035] Preparation of compound II: Compound III (292.6 g, 1.4 mol, 1.0 eq) was dissolved in ethanol, and the reaction solution was cooled to an internal temperature of 10-15 °C with an ice water bath. Then sodium ethoxide (104.7 g, 1.54 mol, 1.1 eq) was added in batches, about 2 g at a time, and the addition was completed in about 1 h, at which time the internal temperature was 14 °C. Then the ice water bath was removed, and the reaction solution was heated with an oil bath, with reflux at an internal temperature of 78 °C. The reflux was maintained for 4 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 500 mL of saturated ammonium chloride solution was added dropwise to the reaction solution, and stirred for 10 min. Then the reaction solution was transferred to a separatory funnel, and extracted with 1 L of petroleum ether once. The aqueous phase was extracted with 1 L of petroleum ether once after separation. The petroleum ether phases were combined and extracted with 300 mL of water once. The petroleum ether phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 166.4 g of a light yellow liquid (Compound II), with a yield of 92.77% and a GC purity of 98.87%.

[0036] Preparation of Compound I: Tetrahydrofuran and water were sequentially added to a four-necked flask, and stirring was started. Then Compound II (140.8 g, 1.1 mol, 1.0 eq) was added in one portion, and p-toluenesulfonic acid (10.3 g, 0.06 mol, 0.05 eq) was added at an internal temperature of 20 °C. The reaction was continued to stir for 2 h. After the reaction was completed, 15 g of sodium carbonate was added to the reaction solution, and stirred for 20 min. The pH was measured to be >7. The reaction solution was distilled under reduced pressure to remove most of the tetrahydrofuran. Then the crude product was poured into a separatory funnel, and 200 mL of water and 600 mL of dichloromethane were added. The aqueous phase was extracted with 400 mL of dichloromethane once. The dichloromethane phases were combined and washed with 100 mL of saturated NaCl solution once. The dichloromethane phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain 87.8 g of a colorless transparent liquid (Compound I), with a yield of 97.35% and a GC purity of 98.23%.

[0037] Comparative Example 1:

[0038] Preparation of Compound IV: In a four-necked flask, add methyl tert-butyl ether, under mechanical stirring, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) in one portion, protect the reaction solution with nitrogen, and cool it in an ice-water bath. When the internal temperature is 5 ℃, add liquid bromine (351.5 g, 2.2 mol, 1.1 eq) dropwise using a constant pressure dropping funnel. It takes about 4 h to complete the dropwise addition, and the reaction solution is slowly warmed to 25 ℃. Continue to stir the reaction at 25 ℃ for 2 h. Then add 1 L saturated sodium bicarbonate aqueous solution to the reaction solution using a constant pressure dropping funnel, and stir for 15 min. After separation, wash the methyl tert-butyl ether phase with 500 mL saturated sodium sulfite solution once. After separation, dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and then remove the methyl tert-butyl ether by distillation under reduced pressure to obtain 210.3 g of a brownish yellow liquid. Distill the crude product under reduced pressure using an oil pump to obtain 173.7 g of a brown liquid (compound IV), with a yield of 53.29% and a GC purity of 95.6%.

[0039] Preparation of compound III: In a four-necked flask, add methyl tert-butyl ether, under mechanical stirring, add cyclopentanone (168.2 g, 2.0 mol, 1.0 eq) in one portion, protect the reaction solution with nitrogen, and cool it in an ice-water bath. When the internal temperature is 5 ℃, add liquid bromine (351.5 g, 2.2 mol, 1.1 eq) dropwise using a constant pressure dropping funnel. It takes about 4 h to complete the dropwise addition, and the reaction solution is slowly warmed to 25 ℃. Continue to stir the reaction at 25 ℃ for 2 h. Then add 1 L saturated sodium bicarbonate aqueous solution to the reaction solution using a constant pressure dropping funnel, and stir for 15 min. After separation, wash the methyl tert-butyl ether phase with 500 mL saturated sodium sulfite solution once. After separation, dry the methyl tert-butyl ether phase with anhydrous sodium sulfate, and then remove the methyl tert-butyl ether by distillation under reduced pressure to obtain 210.3 g of a brownish yellow liquid. Distill the crude product under reduced pressure using an oil pump to obtain 173.7 g of a brown liquid (compound IV), with a yield of 53.29% and a GC purity of 95.6%.

[0040] Preparation of compound II: Compound III (313.5 g, 1.5 mol, 1.0 eq) was dissolved in methanol, and the reaction solution was cooled to an internal temperature of 10-15 °C with an ice water bath. Then sodium methoxide solid (89.1 g, 1.65 mol, 1.1 eq) was added in batches, about 2 g at a time, and the addition was completed in about 1 h, at which time the internal temperature was 14 °C. Then the ice water bath was removed, and the reaction solution was heated with an oil bath, with reflux at an internal temperature of 64 °C. The reflux was maintained for 6 h. After the reaction was completed, the reaction solution was cooled to room temperature, and 500 mL of saturated ammonium chloride solution was added dropwise to the reaction solution, and stirred for 10 min. Then the reaction solution was transferred to a separatory funnel, and extracted with 1 L of petroleum ether once. The aqueous phase was extracted with 1 L of petroleum ether once after separation. The petroleum ether phases were combined and extracted with 300 mL of water once. The petroleum ether phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain a light yellow liquid (Compound II) 179.3 g, with a yield of 93.30% and a GC purity of 98.31%.

[0041] Preparation of Compound I: Tetrahydrofuran and water were sequentially added to a four-necked flask, and stirring was started. Then Compound II (153.8 g, 1.2 mol, 1.0 eq) was added in one portion, and p-toluenesulfonic acid (10.3 g, 0.06 mol, 0.05 eq) was added at an internal temperature of 25 °C. The reaction was continued to stir for 2 h. After the reaction was completed, 15 g of sodium carbonate solid was added to the reaction solution, and stirred for 20 min. The pH was measured to be >7. The reaction solution was distilled under reduced pressure to distill most of the tetrahydrofuran. Then the crude product was poured into a separatory funnel, and 200 mL of water and 600 mL of dichloromethane were added. The aqueous phase was extracted with 400 mL of dichloromethane once. The dichloromethane phases were combined and washed with 100 mL of saturated NaCl solution once. The dichloromethane phase was dried over anhydrous sodium sulfate, and then distilled under reduced pressure to obtain a colorless transparent liquid (Compound I) 94.9 g, with a yield of 96.33% and a GC purity of 98.38%.

[0042] The above detailed description further explains the purpose, technical solutions and beneficial effects of the present application. It should be understood that the above is only a specific embodiment of the present application, and is not intended to limit the protection scope of the present application. Any modification, equivalent replacement, improvement, etc. made on the basis of the technical solutions of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing 2-cyclopentenone, characterized in that, include: ， The brominating agent is N-bromosuccinimide or dibromohydantoin; the acidic catalyst is p-toluenesulfonic acid; and the basic agent is sodium methoxide or sodium ethoxide.

2. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound II from compound III, the organic solvent used in the reaction is methanol or ethanol, and the reaction temperature is 64~78℃.

3. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound II from compound III, the molar ratio of compound III to the basic reagent ranges from 1:1.1 to 1.

2.

4. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound II from compound III, the post-processing steps of the reaction are as follows: after cooling the reaction solution, ammonium chloride is added dropwise to quench the reaction, followed by extraction with petroleum ether, drying, and concentration under reduced pressure to obtain compound II.

5. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound I from compound II, the reaction mixture solvent was tetrahydrofuran and water.

6. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound I from compound II, the reaction temperature is 20~30℃.

7. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound I from compound II, the post-processing steps of the reaction are as follows: the pH value is adjusted to be greater than 7 with sodium carbonate, the reaction solvent is distilled under reduced pressure, extracted with dichloromethane, dried, and concentrated under reduced pressure to obtain compound I.

8. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound IV from compound V, when the brominating agent is dibromohydantoin, the molar ratio of compound V to dibromohydantoin ranges from 1:0.55 to 0.6; when the brominating agent is N-bromosuccinimide, the molar ratio of compound V to N-bromosuccinimide ranges from 1:1.1 to 1.

2.

9. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound IV from compound V, the organic solvent used in the reaction is tertiary methyl ether or dichloromethane.

10. The method for preparing 2-cyclopentenone according to claim 1, characterized in that, In the preparation of compound IV from compound V, the reaction temperature is 20~30℃.

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