A process for the preparation of 2-pentyl-2-cyclopenten-1-one

Abstract

The application discloses a preparation method of 2-pentyl-2-cyclopenten-1-one, which comprises the following steps: under stirring, 2-oxocyclopentane carboxylic acid methyl ester and bromopentane are added dropwise in a mixed solution of a solvent dimethyl sulfoxide and a base, and then a reaction is carried out; after the reaction is completed, the reaction liquid is extracted by filtration, and the filtrate is subjected to vacuum rectification to obtain 2-oxo-1-pentyl cyclopentane methyl carboxylate; 2-oxo-1-pentyl cyclopentane methyl carboxylate is added into an aqueous solution of a base, and decarboxylation hydrolysis, liquid separation, water washing and drying are carried out to obtain 2-pentyl-cyclopentanone; a catalyst diphenyl phosphine and an oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are added into a solvent, 2-pentyl-cyclopentanone is added dropwise, and oxidation is carried out to obtain 2-pentyl-2-cyclopenten-1-one. Compared with an existing synthesis route, the total yield of the application is higher, the problem of low yield in a traditional route is avoided, the solid catalyst and the solvent can be recycled after reaction post-treatment, the reaction post-treatment is simple, and the problem of easy generation of a large amount of waste solid and waste liquid in the traditional route is avoided.

Description

Technical Field

[0001] This invention belongs to the field of chemical organic synthesis technology, specifically relating to a method for preparing 2-pentyl-2-cyclopenten-1-one. Background Technology

[0002] Methyl dihydrojasmonate is one of the most popular synthetic fragrances, favored by perfumers, while 2-pentyl-2-cyclopenten-1-one is an important intermediate in the synthesis of methyl dihydrojasmonate and other fragrances. Its molecular formula is C10H16O, and its relative molecular mass is 152.12. The molecular structural formula of 2-pentyl-2-cyclopenten-1-one is:

[0003]

[0004] The existing methods for preparing 2-pentyl-2-cyclopenten-1-one include the following:

[0005] Method (1) involves reacting butadiene with ethyl acetoacetate under palladium catalysis to obtain chain-like ethyl acetoacetate compounds. These compounds undergo selective hydrogenation, deacylation, hydrolysis, acylation, and cyclization to finally yield the product 2-pentyl-2-cyclopentenone. The reaction equation is shown below:

[0006]

[0007] However, the disadvantages of this route are that it is relatively long, the reaction yield is low (less than 50%), and the metal catalyst used is expensive.

[0008] Method (2) uses α-ethoxycarbonylcyclopentanone as the starting material, which is substituted with 1-bromo-n-pentane. The substitution product is decarboxylated using an aqueous solution of sodium chloride and dimethyl sulfoxide. The decarboxylated product is then chlorinated with a carbon tetrachloride solution of SO2Cl2, and refluxed in a solution of 2,4,6-trimethylpyridine to obtain the product 2-pentyl-2-cyclopenten-1-one. The reaction equation is as follows:

[0009]

[0010] This route has low selectivity, requires the use of thionyl chloride which is highly toxic and dangerous, and has an overall yield of only about 55%. Summary of the Invention

[0011] In view of the deficiencies in the existing technology, the purpose of this invention is to provide a method for preparing 2-pentyl-2-cyclopenten-1-one.

[0012] The technical solution of the present invention is as follows:

[0013] A method for preparing 2-pentyl-2-cyclopenten-1-one includes the following steps:

[0014] 1) Under stirring conditions, methyl 2-oxocyclopentane carboxylate and bromopentane were added dropwise to a mixed solution of dimethyl sulfoxide and alkali. After the reaction was completed, the reaction solution was filtered and the filtrate was distilled under reduced pressure to obtain methyl 2-oxo-1-pentylcyclopentane carboxylate.

[0015] 2) Add methyl 2-oxo-1-pentylcyclopentane carboxylate obtained in step 1) to an aqueous alkaline solution, decarboxylate and hydrolyze, separate the contents, wash with water, and dry to obtain 2-pentyl-cyclopentanone;

[0016] 3) Add the catalyst diphenylphosphine (DPP) and the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to the solvent, and add 2-pentyl-cyclopentanone obtained in step 2) dropwise to oxidize and give 2-pentyl-2-cyclopenten-1-one;

[0017] 4) The alkali in step 1) is sodium carbonate, potassium carbonate, sodium hydroxide, sodium methoxide, or sodium tert-butoxide;

[0018] 5) In step 2), the ingredients are sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

[0019] The reaction equation for this invention is as follows:

[0020]

[0021] Further, the solvent mentioned in step 4) is benzene, acetonitrile, tetrahydrofuran, or dichloromethane.

[0022] Furthermore, in step 1), the molar ratio of methyl 2-oxocyclopentane carboxylate, bromopentane, and base is 1:1~1.5:0.5~1.5, the reaction temperature in step 1) is 30-90℃, and the reaction time after the raw materials are added is 4-12h.

[0023] Furthermore, in step 2), the molar ratio of methyl 2-oxo-1-pentylcyclopentane carboxylate to the base is 1:2~3, the reaction temperature in step 2) is 50~100℃, and the reaction time after the raw materials are added is 4~8h.

[0024] Furthermore, in step 3), the molar ratio of 2-pentyl-cyclopentanone, oxidant, and catalyst is 1:1~1.5:0.05~0.5, the reaction temperature in step 3) is 30~80℃, and the reaction time after the raw materials are added is 12~24h.

[0025] Preferably, in step 1), the molar ratio of methyl 2-oxocyclopentane carboxylate, bromopentane, and alkali is 1:1.1:1, the reaction temperature in step 1) is 35°C, and the reaction time after the raw materials are added is 8 hours.

[0026] Preferably, in step 2), the molar ratio of methyl 2-oxo-1-pentylcyclopentane carboxylate to the base is 1:2.28, the reaction temperature is 90°C, and the reaction time is 6 hours after the raw materials are added.

[0027] Preferably, in step 3), the molar ratio of 2-pentyl-cyclopentanone, oxidant and catalyst is 1:1.05:0.1, the reaction temperature is 40°C, and the reaction time after the raw materials are added is 16 hours.

[0028] The beneficial effects of this invention are as follows:

[0029] 1. The reaction conditions of this invention are mild, the raw materials are inexpensive and readily available, and the operation is simple and quick, making it suitable for industrial production.

[0030] 2. This invention modifies the synthetic route of 2-pentyl-2-cyclopenten-1-one, achieving an overall yield of approximately 75%, which is significantly higher than the approximately 55% yield of the original two synthetic routes. This avoids the problem of low yield associated with traditional routes.

[0031] 3. The present invention allows for the recovery and reuse of solid catalysts and solvents after post-reaction processing, and the post-reaction processing is simple, avoiding the problem of generating large amounts of solid and liquid waste that is common in traditional routes. Implementation

[0032] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0033] Example 1: Synthesis of 2-pentyl-2-cyclopenten-1-one

[0034] A magnetic stir bar was added to a 500 ml three-necked flask, followed by the addition of 69.0 g potassium carbonate and 300 mL DMSO. After stirring at 35 °C for 0.5 h, 71.0 g of methyl 2-oxocyclopentanecarboxylate was added dropwise over 1 h. After the addition was complete, 83.0 g of bromopentane was added dropwise over 1 h after 0.5 h. The reaction was continued at 35 °C for 8 h. The reaction solution was filtered, and the filtrate was distilled under reduced pressure at 138 Pa. The fraction at 80 °C (DMSO) was recovered, and 102.2 g of the fraction at 115 °C was collected. The purity of methyl 2-oxo-1-pentylcyclopentanecarboxylate was 95.2%, and the yield was 92.1%.

[0035] 2-Oxo-1-pentylcyclopentanecarboxylate (colorless, transparent, oily liquid)

[0036] 1H NMR spectrum: 1H NMR (600 MHz, Chloroform-d) δ 3.55 (s, 3H), 2.42 –2.34 (m, 1H), 2.28 – 2.06 (m, 2H), 1.90 – 1.71 (m, 4H), 1.45 – 1.36 (m, 1H), 1.22 – 1.02 (m, 6H), 0.73 (t, J = 7.1 Hz, 3H).

[0037] Carbon NMR spectrum: 13C NMR (151 MHz, CDCl3) δ 214.45, 171.34, 60.38, 52.16, 37.75, 33.73, 32.53, 31.88, 24.33, 22.18, 19.45, 13.73.

[0038] A magnetic stir bar was added to a 500 mL round-bottom flask, followed by the addition of 42.0 g of sodium hydroxide and 220.0 g of water. After stirring to dissolve, 102.2 g of methyl 2-oxo-1-pentylcyclopentanecarboxylate (95.2% purity) was added. The mixture was heated to 90 °C and reacted for 6 h. After the reaction was complete, the mixture was separated into liquid and liquid phases. The lower organic phase was washed with water and dried with anhydrous sodium sulfate to obtain 71.0 g of 2-pentyl-cyclopentanone (96.1% purity, 95.1% yield).

[0039] 2-Pentyl-cyclopentanone NMR data (light yellow transparent oily liquid):

[0040] ¹H NMR spectrum: 600 MHz, Chloroform-d δ 2.24 – 2.10 (m, 2H), 2.05 – 1.88 (m, 3H), 1.74 – 1.63 (m, 2H), 1.45 (qd, J = 10.7, 6.6 Hz, 1H), 1.30 – 1.12 (m, 7H), 0.80 (t, J = 7.0 Hz, 3H).

[0041] Carbon NMR spectrum: 13C NMR (151 MHz, CDCl3) δ 213.42, 49.03, 38.04, 31.70, 29.57, 29.51, 27.13, 22.41, 20.67, 13.89.

[0042] A magnetic stir bar was added to a 500 mL three-necked flask. Then, 8.1 g of diphenylphosphine catalyst, 104.4 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidant, and 200 mL of benzene were added sequentially. After stirring and dissolving, the mixture was heated to 40 °C. Then, 71.0 g of 2-pentyl-cyclopentanone (96.1% purity) was added dropwise over 1 hour. After the addition was complete, the reaction proceeded for another 16 hours. After the reaction was complete, benzene was recovered by rotary evaporation, followed by filtration. The filter cake was used to recover the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The filtrate was then distilled under reduced pressure at 138 Pa, yielding 58.5 g of a fraction at 80 °C with a purity of 96.0% and a yield of 85.0%.

[0043] 2-Pentyl-2-cyclopenten-1-one NMR data (light yellow transparent oily liquid):

[0044] ¹H NMR spectrum: 600 MHz, Chloroform-d δ 7.16 (dq, J = 2.7, 1.3 Hz, 1H), 2.41 (dp, J = 6.7, 2.0 Hz, 2H), 2.24 – 2.20 (m, 2H), 2.03 – 1.97 (m, 2H), 1.32 (p, J = 7.6 Hz, 2H), 1.19 – 1.10 (m, 4H), 0.73 (t, J = 7.1 Hz, 3H).

[0045] Carbon NMR spectrum: 13C NMR (151 MHz, CDCl3) δ 209.63, 157.09, 146.27, 34.38, 31.43, 27.27, 26.25, 24.57, 22.25, 13.78.

[0046] The overall yield of 2-pentyl-2-cyclopenten-1-one synthesized from methyl 2-oxocyclopentanecarboxylate was 74.4%.

[0047] Example 2: Synthesis of 2-pentyl-2-cyclopenten-1-one

[0048] A magnetic stir bar was added to a 500 mL three-necked flask, followed by the sequential addition of 27.0 g sodium methoxide and 300 mL DMSO. The mixture was stirred at 35 °C for 0.5 h, and then 71.0 g of methyl 2-oxocyclopentanecarboxylate was added dropwise over 1 h. After the addition was complete, 83.0 g of bromopentane was added dropwise over 1 h after 0.5 h. The reaction was continued at 35 °C for another 8 h. The reaction mixture was then filtered, and the filtrate was distilled under reduced pressure at 138 Pa. The fraction at 80 °C (DMSO) was recovered, and 100.5 g of the fraction at 115 °C was collected, with a purity of 95.1% and a yield of 90.2%.

[0049] A magnetic stir bar was added to a 500 mL round-bottom flask, followed by the addition of 57.6 g of potassium hydroxide and 270.0 g of water. After stirring to dissolve, 100.5 g of methyl 2-oxo-1-pentylcyclopentanecarboxylate was added. The mixture was heated to 90 °C and reacted for 6 h. After the reaction was complete, the mixture was separated into liquid and liquid phases. The lower organic phase was washed with water and dried over anhydrous sodium sulfate to obtain 69.2 g of 2-pentyl-cyclopentanone with a purity of 96% and a yield of 95.7%.

[0050] A magnetic stir bar was added to a 500 mL three-necked flask. Then, 8.0 g of diphenylphosphine catalyst, 102.8 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidant, and 200 mL of acetonitrile were added sequentially. After stirring and dissolving, the mixture was heated to 40 °C. Then, 69.2 g of 2-pentyl-cyclopentanone was added dropwise over 1 hour. After the addition was complete, the reaction proceeded for another 16 hours. After the reaction was complete, the acetonitrile was recovered by rotary evaporation, followed by filtration. The filter cake was used to recover the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The filtrate was then distilled under reduced pressure at 138 Pa, yielding 57.1 g of the fraction collected at 80 °C with a purity of 96% and a yield of 83.5%.

[0051] The overall yield of 2-pentyl-2-cyclopenten-1-one synthesized from methyl 2-oxocyclopentanecarboxylate was 72.1%.

[0052] Example 3: Synthesis of 2-pentyl-2-cyclopenten-1-one

[0053] A magnetic stir bar was added to a 500 mL three-necked flask, followed by the sequential addition of 48 g of sodium tert-butoxide and 300 mL of DMSO. The mixture was stirred at 35 °C for 0.5 h, and then 71 g of methyl 2-oxocyclopentanecarboxylate was added dropwise over 1 h. After the addition was complete, 83 g of bromopentane was added dropwise over 1 h. The reaction was continued at 35 °C for another 8 h. The reaction mixture was then filtered, and the filtrate was distilled under reduced pressure at 138 Pa. The fraction at 80 °C (DMSO) was recovered, and 103 g of the fraction at 115 °C was collected, with a purity of 95.0% and a yield of 92.2%.

[0054] A magnetic stir bar was added to a 1000 mL round-bottom flask, followed by the addition of 111.4 g of sodium carbonate and 440.3 g of water. After stirring to dissolve, 103.0 g of methyl 2-oxo-1-pentylcyclopentanecarboxylate was added. The mixture was heated to 90 °C and reacted for 6 h. After the reaction was complete, the mixture was separated into liquid and liquid phases. The lower organic phase was washed with water and dried over anhydrous sodium sulfate to obtain 69.2 g of 2-pentylcyclopentanone with a purity of 96.0% and a yield of 93.4%.

[0055] A magnetic stir bar was added to a 500 mL round-bottom flask, followed by the addition of 8.0 g of diphenylphosphine catalyst, 102.6 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidant, and 200 mL of tetrahydrofuran. The mixture was stirred until dissolved, and the temperature was raised to 40 °C. Then, 69.2 g of 2-pentyl-cyclopentanone was added dropwise over 1 hour, followed by a 16-hour reaction. After the reaction was complete, the tetrahydrofuran was recovered by rotary evaporation, and the mixture was then filtered. The filter cake was used to recover the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The filtrate was then distilled under reduced pressure at 138 Pa, yielding 57.6 g of a fraction collected at 80 °C with a purity of 96.2% and a yield of 84.7%.

[0056] The overall yield of 2-pentyl-2-cyclopenten-1-one synthesized from methyl 2-oxocyclopentanecarboxylate was 72.9%.

[0057] Example 4: Synthesis of 2-pentyl-2-cyclopenten-1-one

[0058] A magnetic stir bar was added to a 500 mL three-necked flask. 20.0 g of sodium hydroxide and 300 mL of DMSO were added sequentially. After stirring at 35 °C for 0.5 h, 71.0 g of methyl 2-oxocyclopentanecarboxylate was added dropwise over 1 h. 0.5 h after the addition was complete, 83.0 g of bromopentane was added dropwise over 1 h. After the addition was complete, the reaction was continued at 35 °C for 8 h. The reaction solution was filtered, and the filtrate was distilled under reduced pressure at 138 Pa. The fraction at 80 °C (DMSO) was recovered, and 104.3 g of the fraction at 115 °C was collected, with a purity of 95.2% and a yield of 93.5%.

[0059] A magnetic stir bar was added to a 500 mL round-bottom flask, followed by the addition of 147.3 g of potassium carbonate and 580.3 g of water. After stirring to dissolve, 104.3 g of methyl 2-oxo-1-pentylcyclopentanecarboxylate was added. The mixture was heated to 90 °C and reacted for 6 h. After the reaction was complete, the mixture was separated into liquid and liquid phases. The lower organic phase was washed with water and dried over anhydrous sodium sulfate to obtain 70.2 g of 2-pentylcyclopentanone with a purity of 96.0% and a yield of 93.4%.

[0060] A magnetic stir bar was added to a 500 mL three-necked flask. Then, 8.0 g of diphenylphosphine catalyst, 104.1 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidant, and 200 mL of dichloromethane were added sequentially. After stirring and dissolving, the mixture was heated to 40 °C, and then 70.2 g of 2-pentyl-cyclopentanone was added dropwise over 1 hour. After the addition was complete, the reaction proceeded for another 16 hours. After the reaction was complete, dichloromethane was recovered by rotary evaporation, followed by filtration. The filter cake was used to recover the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The filtrate was then distilled under reduced pressure at 138 Pa, yielding 57.6 g of a fraction collected at 80 °C with a purity of 96.0% and a yield of 83.2%.

[0061] The overall yield of 2-pentyl-2-cyclopenten-1-one synthesized from methyl 2-oxocyclopentanecarboxylate was 72.7%.

Claims

1. A method for preparing 2-pentyl-2-cyclopenten-1-one, characterized in that, Includes the following steps: 1) Under stirring conditions, methyl 2-oxocyclopentane carboxylate and bromopentane were added dropwise to a mixed solution of dimethyl sulfoxide and alkali. The reaction temperature was 35℃. After the reaction was completed, the reaction solution was filtered and the filtrate was distilled under reduced pressure to obtain methyl 2-oxo-1-pentylcyclopentane carboxylate. 2) Add methyl 2-oxo-1-pentylcyclopentane carboxylate obtained in step 1) to an aqueous alkaline solution, decarboxylate and hydrolyze, separate the contents, wash with water, and dry to obtain 2-pentyl-cyclopentanone; 3) Add the catalyst diphenylphosphine and the oxidant 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to the solvent, and add 2-pentyl-cyclopentanone obtained in step 2) dropwise to oxidize and give 2-pentyl-2-cyclopenten-1-one; The base in step 1) is sodium carbonate, potassium carbonate, sodium hydroxide, sodium methoxide, or sodium tert-butoxide; The alkali in step 2) is sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate; The reaction temperature in step 3) is 30~80℃. The solvent mentioned in step 3) is benzene, acetonitrile, tetrahydrofuran, or dichloromethane.

2. The preparation method according to claim 1, characterized in that, In step 1), the molar ratio of methyl 2-oxocyclopentane carboxylate, bromopentane, and alkali is 1:1~1.5:0.5~1.5, and the reaction time after the raw materials are added is 4-12 hours.

3. The preparation method according to claim 1, characterized in that, In step 2), the molar ratio of methyl 2-oxo-1-pentylcyclopentane carboxylate to the base is 1:2~3. The reaction temperature in step 2) is 50~100℃, and the reaction time after the raw materials are added is 4~8h.

4. The preparation method according to claim 1, characterized in that, In step 3), the molar ratio of 2-pentyl-cyclopentanone, oxidant and catalyst is 1:1~1.5:0.05~0.5, and the reaction time after the raw materials are added is 12~24h.

5. The preparation method according to claim 2, characterized in that, In step 1), the molar ratio of methyl 2-oxocyclopentane carboxylate, bromopentane, and alkali is 1:1.1:1, and the reaction time is 8 hours after the raw materials are added.

6. The preparation method according to claim 3, characterized in that, In step 2), the molar ratio of methyl 2-oxo-1-pentylcyclopentane carboxylate to the base is 1:2.28, the reaction temperature is 90℃, and the reaction time is 6 hours after the raw materials are added.

7. The preparation method according to claim 4, characterized in that, In step 3), the molar ratio of 2-pentyl-cyclopentanone, oxidant and catalyst is 1:1.05:0.1, the reaction temperature is 40℃, and the reaction time is 16h after the raw materials are added dropwise.

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