A method for generating cyclopropyl methyl ketone by catalyzing 5-chloro-2-pentanone with a deep eutectic solvent
The cyclization of 5-chloro-2-pentanone by catalyzing cyclization of 5-chloro-2-pentanone in cyclopropyl methyl ketone synthesis method is solved, and high efficiency and low-cost rings are achieved Propyl methyl ketone preparation, suitable for industrial production.
Patent Information
- Application Number
- CN202310550731.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-16
- Publication Date
- 2024-12-20
- Estimated Expiration
- 2043-05-16
AI Technical Summary
The existing cyclopropyl methyl ketone synthesis methods have complex processes, long production cycles, many by-products, and doped with metal ions in the product, resulting in high production costs and difficult industrial production.
The cyclization of 5-chloro-2-pentanone by a ternary eutectic solvent is catalyzed to form cyclopropyl methyl ketone, and the product is directly prepared through a one-step method without metal ion doping, and the catalytic efficiency of the ternary eutectic solvent is high, and the reaction is The conditions are mild and the catalytic system can be recycled.
It shortens the production cycle of the product, reduces the cost of raw materials, increases the conversion rate of raw materials, reduces by-products, meets the requirements of industrial production, and improves the purity of the product.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for cyclizing 5-chloro-2-pentanone to generate cyclopropyl methyl ketone by catalyzing the cyclization of 5-chloro-2-pentanone with a ternary low eutectic solvent. Background Art
[0002] Cyclopropylmethylketone (CPMK) has a molecular formula of C5H8O. The chemical structure of CPMK shows that it has a chain structure and has both cyclopropyl and carbonyl structures, which is the main factor affecting its chemical properties. Cyclopropyl is a very important pharmacophoric group. Many compounds containing this structure show a variety of biological activities such as antifungal, antiviral, antitumor, and insecticide. Therefore, CPMK is often used as an intermediate to synthesize the anti-AIDS drug efavirenz, the green pesticide fungicide cyproconazole, and the plant growth regulator cyproconazole. Therefore, the research on the industrial synthesis method of CPMK has very important practical significance.
[0003] The commonly used method for preparing cyclopropyl methyl ketone is to use 2-methylfuran to hydrogenate to prepare 2-methyl-4,5-dihydrofuran, and then react with hydrochloric acid to undergo a ring-opening chlorination reaction, followed by a cyclization reaction catalyzed by an inorganic base to generate cyclopropyl methyl ketone. This synthesis method has a complex process flow, a long production cycle, many by-products, and products doped with metal ion impurities, which has brought many troubles to the industrial production of cyclopropyl methyl ketone. How to shorten the reaction cycle and reduce by-products has become a technical problem that needs to be solved urgently in production.
[0004] Another synthesis method is to use o-phenylenediamine and cyclopropylcarboxylic acid as raw materials, polyphosphoric acid as catalyst, synthesize cyclopropylbenzimidazole under microwave radiation, quaternize with iodomethane to obtain cyclopropylbenzimidazole salt, and then add Grignard reagent and hydrolyze to prepare cyclopropyl methyl ketone. This synthesis method has many by-products and low conversion rate of target product, which greatly increases production cost and is not conducive to industrial production.
[0005] Therefore, there is still a need in the art to explore a method for synthesizing cyclopropyl methyl ketone with mild reaction conditions, high catalytic efficiency, no metal ion doping, high atom economy, recyclable catalytic system, and suitable for industrial scale-up production. Summary of the invention
[0006] In view of the problems in the current synthesis method of cyclopropyl methyl ketone, such as high raw material cost, complex process operation, many by-products, product doped with metal elements, and high difficulty in industrial scale-up production, the present invention provides a method for cyclizing 5-chloro-2-pentanone to produce cyclopropyl methyl ketone using a ternary deep eutectic solvent.
[0007] In order to achieve the above object, the present invention adopts the following technical solutions:
[0008] The method for cyclizing 5-chloro-2-pentanone to generate cyclopropyl methyl ketone by catalyzing the ternary deep eutectic solvent comprises the following steps:
[0009] Step 1, mixing 5-chloro-2-pentanone and a ternary low eutectic solvent, heating and reacting, and cooling to room temperature after the reaction to obtain a crude cyclopropyl methyl ketone product;
[0010] Step 2, purifying the crude cyclopropyl methyl ketone product to obtain cyclopropyl methyl ketone, and removing the hydrogen chloride by heating the ternary low eutectic solvent for reduction, and the system can be recycled.
[0011] Furthermore, the hydrogen bond acceptors of the ternary deep eutectic solvent in step 1 are choline chloride and choline hydroxide.
[0012] Furthermore, the first hydrogen bond donor of the ternary deep eutectic solvent in step 1 is any one of urea, glycerol, thiourea, ethylenediamine, ethylene glycol, and ethanolamine. The molar ratio of the hydrogen bond acceptor to the first donor in the ternary deep eutectic solvent in step 1 is 1:(1-2).
[0013] Furthermore, the second hydrogen bond donor of the ternary deep eutectic solvent in step 1 is any one of lysine, arginine and histidine. The molar ratio of the hydrogen bond acceptor to the second hydrogen bond donor in the ternary deep eutectic solvent in step 1 is 1:(0.05-0.2).
[0014] Furthermore, in step 1, the mass ratio of 5-chloro-2-pentanone to the ternary low eutectic solvent is 1:(1-10).
[0015] Furthermore, the catalytic reaction temperature in step 1 is 40 to 80°C.
[0016] Furthermore, the catalytic reaction time in step 1 is 1 to 2 hours.
[0017] Furthermore, the crude cyclopropyl methyl ketone product obtained in step 1 has a yield of 97% to 99.3%.
[0018] Furthermore, the purification method in step 2 is distillation.
[0019] Furthermore, the cyclopropyl methyl ketone obtained in step 2 has a product yield of 96% to 99.1%.
[0020] Compared with the prior art, the present invention has the following advantages:
[0021] 1. The present invention directly prepares cyclopropyl methyl ketone by a one-step method without metal ion doping, and the ternary deep eutectic solvent has high catalytic efficiency, thereby shortening the production cycle of the product.
[0022] 2. The present invention uses 5-chloro-2-pentanone as a reaction raw material, which is green and environmentally friendly, has low raw material cost, and also meets the requirements of atom economy in green chemistry.
[0023] 3. The present invention adopts catalytic cyclization to synthesize cyclopropyl methyl ketone. There are no by-products in the production process, and the raw material conversion rate is high. The catalytic system can be recycled to meet the requirements of industrial production, and the purity of the obtained refined product also meets industrial requirements. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 :Schematic diagram of the process of preparing cyclopropyl methyl ketone by cyclization of 5-chloro-2-pentanone catalyzed by a ternary deep eutectic solvent.
[0025] Figure 2 :Taking the ternary low eutectic solvent choline chloride-urea-arginine as an example of the catalytic reaction process, the yield of cyclopropyl methyl ketone changes with temperature and time.
[0026] Figure 3 : H NMR spectrum of cyclopropyl methyl ketone.
[0027] Figure 4 : C NMR spectrum of cyclopropyl methyl ketone. DETAILED DESCRIPTION
[0028] The method for cyclizing 5-chloro-2-pentanone to generate cyclopropyl methyl ketone by catalyzing the ternary deep eutectic solvent comprises the following steps:
[0029] Step 1, mixing 5-chloro-2-pentanone and a ternary low eutectic solvent, heating and reacting, and cooling to room temperature after the reaction to obtain a crude cyclopropyl methyl ketone product;
[0030] Step 2, distilling and purifying the crude cyclopropyl methyl ketone product to obtain cyclopropyl methyl ketone, the ternary low eutectic solvent can be heated to remove the hydrogen chloride reduction, and the system can be recycled.
[0031] Example 1
[0032] 2 g 5-chloro-2-pentanone and 2 g choline chloride-urea-arginine (1:1:0.05) were added to a 50 mL round-bottom flask. After stirring and heating at 40 ° C for 1 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 97%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 96%.
[0033] Example 2
[0034] 2 g 5-chloro-2-pentanone and 20 g choline chloride-urea-arginine (1:2:0.2) were added to a 50 mL round-bottom flask. After stirring and heating at 80 ° C for 2 h, the reaction was completed, heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 99.3%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with the structure shown in Figure 3 , 4 As shown, the yield was 99.1%.
[0035] Example 3
[0036] 2 g 5-chloro-2-pentanone and 6 g choline chloride-glycerol-lysine (1:1.5:0.15) were added to a 50 mL round-bottom flask. After stirring and heating at 50 ° C for 1.5 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 97.2%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 96.7%.
[0037] Example 4
[0038] 2 g 5-chloro-2-pentanone and 4 g choline chloride-thiourea-histidine (1:2:0.1) were added to a 50 mL round-bottom flask. After stirring and heating at 65 ° C for 2 h, the reaction was completed, heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 98.7%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 97.5%.
[0039] Example 5
[0040] 2 g 5-chloro-2-pentanone and 15 g choline chloride-ethylene glycol-lysine (1:1:0.15) were added to a 50 mL round-bottom flask. After stirring and heating at 70 ° C for 1.5 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 97.9%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 96.1%.
[0041] Example 6
[0042] 2 g of 5-chloro-2-pentanone and 5 g of choline hydroxide-ethylenediamine-arginine (1:1:0.1) were added to a 50 mL round-bottom flask. After stirring and heating at 80 ° C for 2 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 98.3%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3, 4 As shown, the yield was 96.9%.
[0043] Example 7
[0044] 2 g 5-chloro-2-pentanone and 4 g choline hydroxide-ethanolamine-histidine (1:2:0.05) were added to a 50 mL round-bottom flask. After stirring and heating at 55 ° C for 1 h, the reaction was completed, heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 99.2%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 96.9%.
[0045] Example 8
[0046] 2 g 5-chloro-2-pentanone and 18 g choline hydroxide-urea-histidine (1:1:0.05) were added to a 50 mL round-bottom flask. After stirring and heating at 70 ° C for 1.5 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 98.4%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown in Figure 3 , 4 As shown, the yield was 97.1%.
[0047] Example 9
[0048] 2 g of 5-chloro-2-pentanone and 13 g of choline hydroxide-ethylenediamine-lysine (1:2:0.15) were added to a 50 mL round-bottom flask. After stirring and heating at 50 ° C for 1 h, the reaction was completed, and the heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 98.9%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with the structure shown in Figure 3 , 4 As shown, the yield was 97.6%.
[0049] Example 10
[0050] 2 g of 5-chloro-2-pentanone and 5 g of choline hydroxide-thiourea-arginine (1:1:0.15) were added to a 50 mL round-bottom flask. After stirring and heating at 70 ° C for 2 h, the reaction was completed, heating was stopped and cooled to room temperature to obtain a crude cyclopropyl methyl ketone product with a yield of 97.3%. The crude product was distilled and purified to obtain cyclopropyl methyl ketone with a structure as shown below: Figure 3 , 4 As shown, the yield was 96.2%.
[0051] The contents not described in detail in the specification of the present invention belong to the prior art known to the professional and technical personnel in the field. Although the illustrative specific embodiments of the present invention are described above to facilitate the understanding of the present invention by the technical personnel in the field, it should be clear that the present invention is not limited to the scope of the specific embodiments. For the ordinary technical personnel in the field, as long as various changes are within the spirit and scope of the present invention defined and determined by the attached claims, these changes are obvious, and all inventions and creations using the concept of the present invention are protected.
Claims
1. A method for catalyzing 5-chloro-2-pentanone to produce cyclopropyl methyl ketone using a deep eutectic solvent, characterized in that: The following steps are involved: Step 1, mixing 5-chloro-2-pentanone and a ternary low eutectic solvent, heating and reacting, and cooling to room temperature after the reaction is completed to obtain a crude cyclopropyl methyl ketone product; Step 2, purifying the crude cyclopropyl methyl ketone product to obtain cyclopropyl methyl ketone, the ternary deep eutectic solvent can be heated to remove hydrogen chloride reduction, and the system can be recycled; The ternary deep eutectic solvent consists of a hydrogen bond acceptor, a first hydrogen bond donor and a second hydrogen bond donor; The hydrogen bond acceptors of the ternary deep eutectic solvent in step 1 are choline chloride and choline hydroxide; In the step 1, the first hydrogen bond donor of the ternary deep eutectic solvent is any one of urea, glycerol, thiourea, ethylenediamine, ethylene glycol, and ethanolamine, and the second hydrogen bond donor is any one of lysine, arginine, and histidine.
2. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 1, characterized in that: In the step 1, the molar ratio of the hydrogen bond acceptor to the first donor in the ternary deep eutectic solvent is 1:(1-2), and the molar ratio of the hydrogen bond acceptor to the second donor is 1:(0.05-0.2).
3. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to any one of claims 1 and 2, characterized in that: In the step 1, the mass ratio of 5-chloro-2-pentanone to the ternary low eutectic solvent is 1:(1-10).
4. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 3, characterized in that: The catalytic reaction temperature described in step 1 is 40-80°C.
5. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 3, characterized in that: The catalytic reaction time described in step 1 is 1 to 2 hours.
6. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 3, characterized in that: The crude cyclopropyl methyl ketone product obtained in step 1 has a product yield of 97% to 99.3%.
7. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 1, characterized in that: The purification method in step 2 is distillation.
8. The method for producing cyclopropyl methyl ketone from 5-chloro-2-pentanone catalyzed by a deep eutectic solvent according to claim 7, characterized in that: The cyclopropyl methyl ketone obtained in step 2 has a product yield of 96% to 99.1%.