Synthetic method of alpha-methyl ketone

Abstract

The invention discloses a synthetic method of alpha-methyl ketone. The synthetic method comprises the following steps: # imgabs0 #; in the synthesis formula, R is alkyl or aryl; r'is alkyl or aryl; the preparation method comprises the following steps: adding ketone and MeI into a reaction container according to a molar ratio of 1: 1.0 to 1: 1.5; adding a solvent, and stirring; sequentially adding a copper catalyst, a ligand and alkali, and heating for reaction; after the reaction is finished, cooling to 23-25 DEG C, quenching, extracting with ethyl acetate, drying and desolventizing to obtain a crude product; and finally rectifying and purifying to obtain the product. According to the method, the copper catalyst and the ligand are combined, so that the reaction between ketone and methyl iodide can be promoted under mild conditions, and the whole process is more stable and controllable. The method not only improves the selectivity and yield of the reaction, but also ensures the consistency of the product quality, and avoids the product performance fluctuation caused by difficult control of the reaction conditions in the traditional method.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing alpha-methyl ketone. Background Art

[0002] In the chemical industry, α-methyl ketones play an indispensable role, with applications ranging from synthetic intermediates to pharmaceutical ingredients, fragrances, and materials science. However, despite their importance, traditional production methods face many challenges that limit their wider application and economic benefits.

[0003] Traditionally, the manufacturing process of α-methyl ketone is often complicated, involving a multi-step synthesis path, which not only increases the difficulty of production, but also affects the overall yield. At the same time, due to the low selectivity of the reaction, a variety of by-products are easily produced in this process, which brings additional troubles to the subsequent separation and purification. In addition, the control of the reaction conditions is not precise enough, resulting in fluctuations in product quality, which in turn affects the performance and consistency of the final product. It is worth noting that in order to maintain the necessary reaction conditions, such as temperature, a higher energy input is usually required, which undoubtedly increases the cost of production.

[0004] Taking these factors into consideration, the existing production method makes the cost of α-methyl ketone high, which has a negative impact on market competitiveness. Therefore, it is particularly important to develop a more optimized synthesis route. The ideal new synthesis method should simplify the production process, improve reaction efficiency and selectivity, reduce unnecessary by-products, and reduce energy consumption to achieve effective cost control. Through such improvements, not only can product quality be improved, but also market demand can be better met and the development of related industries can be promoted. Summary of the invention

[0005] The purpose of the present invention is to provide a method for synthesizing α-methyl ketone, use specific catalysts and ligands, accurately control the reaction conditions, and provide an efficient and economical synthesis method, thereby promoting the industrialization process of α-methyl ketone.

[0006] The technical solution adopted by the present invention to solve the technical problem is a method for synthesizing α-methyl ketone, comprising the following steps: ;

[0007] In the synthetic formula, R is an alkyl group or an aryl group; R' is an alkyl group or an aryl group; Add ketone and MeI into a reaction vessel in a molar ratio of 1:1.0 to 1:1.5; Add solvent and stir; Adding a copper catalyst, a ligand and a base in sequence, and heating to react; After the reaction is completed, the temperature is cooled to 23-25°C, quenched, extracted with ethyl acetate, dried, and desolventized to obtain a crude product; Finally, the product is obtained by distillation and purification.

[0008] Furthermore, the solvent is N,N-dimethylformamide, toluene, trifluorotoluene, chlorobenzene or 1, 4-dioxane.

[0009] Furthermore, the copper catalyst is cuprous iodide, cuprous bromide or cuprous chloride.

[0010] Furthermore, the ligand is bipyridine or 1,10-phenanthroline.

[0011] Furthermore, the base is potassium carbonate, sodium carbonate, potassium phosphate, cesium carbonate, sodium hydroxide, potassium hydroxide or potassium tert-butoxide.

[0012] Furthermore, the reaction temperature is 80-120°C.

[0013] The beneficial effects of the present invention are: (1) The present invention uses a highly efficient copper catalyst and ligand combination to promote the reaction between ketone and methyl iodide under mild conditions, making the entire process more stable and controllable. This not only improves the selectivity and yield of the reaction, but also ensures the consistency of product quality, avoiding product performance fluctuations caused by difficult-to-control reaction conditions in traditional methods.

[0014] (2) By simplifying the synthesis path and reducing unnecessary steps, the new process route effectively shortens the production cycle and reduces the complexity of operation. The synthesis method of the present invention can reduce equipment investment and maintenance costs, while improving the flexibility and response speed of the production line, which is particularly important for large-scale industrial production.

[0015] (3) The present invention pays special attention to environmental protection and sustainable development. By reducing energy consumption and waste emissions, the new method conforms to the concept of modern green chemistry. In particular, the solvents, catalysts and other materials used are easy to recycle, further reducing the environmental burden.

[0016] (4) From an economic perspective, the new process of the present invention greatly reduces the cost of raw materials and energy consumption, making the price of the final product more competitive. The high yield and high quality product characteristics also help to open up a broader market space and bring greater profit margins to manufacturers. DETAILED DESCRIPTION

[0017] The technical solution of the present invention is further described in detail below through specific embodiments.

[0018] In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or are commonly used in the art. The methods in the following embodiments, unless otherwise specified, are all conventional methods in the art.

[0019] Embodiment 1:

[0020] Add 1.0 mmol cyclopentanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL N,N-dimethylformamide, add 0.05mmol cuprous iodide, 0.1mmol bipyridine and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by reduced pressure distillation to obtain a crude product. The crude product is distilled to obtain the product with a yield of 85%.

[0021] Embodiment 2:

[0022] Add 1.0 mmol cyclohexanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL N,N-dimethylformamide, add 0.05mmol cuprous iodide, 0.1mmol bipyridine and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Distill under reduced pressure to remove the solvent to obtain a crude product. The crude product is distilled to obtain the product with a yield of 86%.

[0023] Embodiment 3:

[0024] Add 1.0 mmol cycloheptanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL toluene, add 0.05mmol cuprous iodide, 0.1mmol bipyridine and 2.0mmol sodium carbonate to the above mixture while stirring. Heat the mixture to 110°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, the reaction system is cooled to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Distill under reduced pressure to remove the solvent to obtain a crude product. The crude product is distilled to obtain the product with a yield of 81%.

[0025] Embodiment 4:

[0026] Add 1.0 mmol cyclooctanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL toluene, add 0.05mmol cuprous iodide, 0.1mmol 1,10-phenanthroline and 2.0mmol potassium phosphate to the above mixture while stirring. Heat the mixture to 90°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 89%.

[0027] Embodiment 5:

[0028] Add 1.0 mmol of 12-membered cyclic ketone into a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL toluene, add 0.05mmol cuprous bromide, 0.1mmol 1,10-phenanthroline and 2.0mmol cesium carbonate to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 77%.

[0029] Embodiment 6:

[0030] Add 1.0 mmol of indanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL1, 4-dioxane, add 0.05mmol cuprous iodide, 0.1mmol bipyridine and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 77%.

[0031] Embodiment 7:

[0032] Add 1.0 mmol 1-tetralone into a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL 1, 4-dioxane, add 0.05mmol cuprous chloride, 0.1mmol bipyridine and 2.0mmol potassium tert-butoxide to the above mixture while stirring. Heat the mixture to 100°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, the reaction system is cooled to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 77%.

[0033] Embodiment 8:

[0034] Add 1.0 mmol of pentanone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL trifluorotoluene, add 0.05mmol cuprous iodide, 0.1mmol 1,10-phenanthroline and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 100°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 88%.

[0035] Embodiment 9:

[0036] Add 1.0 mmol of phenylacetone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL trifluorotoluene, add 0.05mmol cuprous iodide, 0.1mmol 1,10-phenanthroline and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 110°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by distillation under reduced pressure to obtain a crude product. The crude product is distilled to obtain the product with a yield of 89%.

[0037] Embodiment 10:

[0038] Add 1.0 mmol of dibenzoyl acetophenone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL chlorobenzene, add 0.05mmol cuprous iodide, 0.1mmol bipyridine and 2.0mmol potassium carbonate to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, the reaction system is cooled to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Distill under reduced pressure to remove the solvent to obtain a crude product. The crude product is distilled to obtain the product with a yield of 75%.

[0039] Embodiment 11:

[0040] Add 1.0 mmol of benzophenone to a clean, dry 1000 ml reaction bottle. , 1.2mmol iodomethane and 10mL N,N-dimethylformamide, add 0.05mmol cuprous bromide, 0.1mmol 1,10-phenanthroline and 2.0mmol potassium hydroxide to the above mixture while stirring. Heat the mixture to 80°C and stir the reaction at this temperature. Use central control monitoring means to monitor the progress of the reaction until the reaction is completed. After the reaction is completed, cool the reaction system to 25°C. Add an appropriate amount of water to quench the reaction, and then extract the product with ethyl acetate. Combine the organic phases and dry to remove moisture. Remove the solvent by reduced pressure distillation to obtain a crude product. The crude product is distilled to obtain the product with a yield of 72%.

[0041] Through detailed research and experimental verification of multiple embodiments, the present invention provides a novel and efficient method for synthesizing α-methyl ketone. The method successfully promotes the reaction between ketone and methyl iodide under mild conditions by using a specific copper catalyst (such as cuprous iodide, cuprous bromide or cuprous chloride) and a ligand (such as bipyridine or 1,10-phenanthroline), thereby improving the selectivity and yield of the reaction and ensuring the consistency of product quality.

[0042] The results of the examples show that the method of the present invention not only simplifies the synthesis path, reduces unnecessary steps, effectively shortens the production cycle, reduces the complexity of operation, but also significantly reduces the generation of by-products. This shows that the new process route can reduce equipment investment and maintenance costs, while improving the flexibility and response speed of the production line, which is particularly important for large-scale industrial production.

[0043] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for synthesizing α-methyl ketone, characterized in that: The following steps are involved: ； In the synthetic formula, R is an alkyl group or an aryl group; R' is an alkyl group or an aryl group; Add ketone and MeI into a reaction vessel in a molar ratio of 1:1.0 to 1:1.5; Add solvent and stir; Adding a copper catalyst, a ligand and a base in sequence, and heating to react; After the reaction is completed, the temperature is cooled to 23-25°C, quenched, extracted with ethyl acetate, dried, and desolventized to obtain a crude product; Finally, the product is obtained by distillation and purification.

2. The method for synthesizing an α-methyl ketone according to claim 1, characterized in that: The ketone is cyclopentanone, cyclohexanone, cyclohexanone, twelve-membered ring ketone, indanone, 1-tetralone, pentanone, propiophenone, diacetophenone or octanophenone.

3. The method for synthesizing an α-methyl ketone according to claim 1, characterized in that: The solvent is N,N-dimethylformamide, toluene, trifluorotoluene, chlorobenzene or 1, 4-dioxane.

4. The method for synthesizing an α-methyl ketone according to claim 1, characterized in that: The copper catalyst is cuprous iodide, cuprous bromide or cuprous chloride.

5. The method for synthesizing α-methyl ketone according to claim 1, characterized in that: The ligand is bipyridine or 1,10-phenanthroline.

6. The method for synthesizing α-methyl ketone according to claim 1, characterized in that: The base is potassium carbonate, sodium carbonate, potassium phosphate, cesium carbonate, sodium hydroxide, potassium hydroxide or potassium tert-butoxide.

7. The method for synthesizing α-methyl ketone according to claim 1, characterized in that: The reaction temperature is 80-120°C.

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