Synthetic method of p-methoxycyclohexanone

Abstract

The invention relates to the field of organic synthesis, in particular to a synthetic method of p-methoxycyclohexanone, which comprises the following steps: (1) reacting vinyl methyl ether with 2-trimethylsiloxy-1, 3-butadiene to generate 1-trimethylsiloxy-4-methoxycyclohexene; and (2) carrying out an acidification reaction on the 1-(trimethylsiloxy-4-methoxycyclohexene, so as to generate the p-methoxycyclohexanone. P-methoxycyclohexanone is a fine chemical engineering intermediate widely applied to the fields of medicines and pesticides, particularly a key intermediate of a novel insecticide spirotetramat, the invention provides a new method for synthesizing the P-methoxycyclohexanone, the process route is novel, raw material reagents are easy to obtain, the use of highly toxic reagents and expensive catalysts is avoided, and the method is suitable for industrial production. The defects in the prior art are overcome, and the industrial value is achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organic synthesis, in particular to a synthesis method of p-methoxy cyclohexanone. BACKGROUND

[0002] P-methoxy cyclohexanone is an important fine chemical intermediate, which is widely used in the field of medicine and pesticide, especially, it is a key intermediate of a new type of insecticide spirotetramat, which is the only insecticide with bidirectional systemic transmission performance so far.

[0003] As for the synthesis technology of p-methoxy cyclohexanone, the following methods are mainly referred to in the domestic and foreign literatures:

[0004] 1. Patent WO2007107565A1 reports that 1,4-cyclohexanedione monoethylene glycol ketal is used as a starting material, which is reduced by NaBH4, methylated, and hydrolyzed in three steps to prepare p-methoxy cyclohexanone. This method has the following problems: the starting material 1,4-cyclohexanedione monoethylene glycol ketal cannot be produced on a large scale, and is not easy to obtain; the methylating reaction needs to be carried out in a strong alkaline system, and a large amount of salt-containing wastewater is generated in the post-treatment; the ethylene glycol generated in the hydrolysis step is mixed in the wastewater, which is difficult to recover; and the wastewater has a high COD and is difficult to treat.

[0005]

[0006] 2. The literature (Journal of Medicinal Chemistry (1989), 32(2), 351-357) reports that 1,4-cyclohexanediol is used as a starting material, which is methylated and oxidized in two steps to prepare p-methoxy cyclohexanone. This literature uses methyl iodide as a methylating agent, which has a high toxicity, and needs to be carried out in a strong alkaline system, resulting in polymerization of the starting material and the product, and greatly reducing the yield. In addition, the oxidizing agent PCC is expensive, and a large amount of salt-containing wastewater is generated in the post-treatment.

[0007]

[0008] 3. The literature (Tetrahedron Letters. 1994, 35(39), 7151-7154) reports that 4-methoxy phenol is used as a starting material, which is reduced by rhodium and aluminum oxide, and then prepared into p-methoxy cyclohexanone by using sodium bromate as an oxidizing agent and cerium nitrate as a catalyst. This method has the following problems: the cost of the starting material is high; and a large amount of salt-containing wastewater is generated in the post-treatment.

[0009]

[0010] 4. Patent CN1137513A reports that p-methoxyphenol is used as raw material, and the product p-methoxycyclohexanone is directly obtained by hydrogenation reduction under the condition of palladium-carbon and borax, but the process control is difficult, the raw material conversion effect is not good, the by-product is much, and the operation is complicated.

[0011]

[0012] In summary, the preparation methods have problems of difficult raw material, expensive catalyst and oxidant, low yield of synthetic product, high COD of wastewater difficult to handle, heavy metal pollution of wastewater, etc. SUMMARY

[0013] In order to overcome the above-mentioned deficiencies in the prior art, the purpose of the present application is to provide a method for synthesizing p-methoxycyclohexanone, which is easy to obtain raw materials, easy to handle wastewater, and does not use toxic reagents and expensive catalysts in the reaction process.

[0014] The technical solution of the present application to solve the above technical problems is as follows:

[0015] The present application provides a method for synthesizing p-methoxycyclohexanone, comprising the following steps:

[0016] (1) vinyl methyl ether reacts with 2-trimethylsiloxy-1,3-butadiene to form 1-trimethylsiloxy-4-methoxycyclohexene;

[0017] (2) 1-trimethylsiloxy-4-methoxycyclohexene is subjected to acidification reaction to form p-methoxycyclohexanone;

[0018] The specific reaction formula is as follows:

[0019]

[0020] Further, the reaction pressure in step (1) is 0.5 MPa to 5.0 MPa;

[0021] Further, the reaction temperature in step (1) is 150℃ to 200℃;

[0022] Further, the reaction solvent in step (1) is one or more of xylene, mixed xylene and chlorobenzene.

[0023] Further, the acid used in step (2) is a commonly used inorganic acid such as hydrochloric acid, sulfuric acid and phosphoric acid.

[0024] Further, the molar ratio of 1-trimethylsiloxy-4-methoxycyclohexene to acid in step (2) is 1:0.01 to 0.1.

[0025] Further, the mass volume of 2-trimethylsiloxy-1,3-butadiene and solvent in step (1) is 1:4-5.

[0026] Further, the reaction temperature in step (2) is 30-40°C.

[0027] Further, the concentration of acid in step (2) is 10%-30%.

[0028] Further, the reaction solvent in step (2) is a halogenated hydrocarbon solvent such as dichloromethane or 1,2-dichloroethane.

[0029] In the present application, if the Chinese name of the compound conflicts with the structural formula, the structural formula is used as the standard; if the structural formula is obviously incorrect, the Chinese name is used as the standard.

[0030] The present application has the advantages of avoiding the use of highly toxic reagents and expensive catalysts, the raw reagents are easy to obtain, the process is environmentally friendly, the wastewater is less and easy to treat, the process is simplified, the shortcomings of the prior art are overcome, and the process is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0031] The present application is described below in conjunction with examples, but the present application is not limited thereto. Simple substitutions or improvements made by those skilled in the art to the present application are within the scope of the technical solutions protected by the present application.

[0032] Example 1

[0033] In a 500 mL autoclave, 200 mL of mixed xylene, 50 g of 2-trimethylsiloxy-1,3-butadiene, vacuum and vinyl methyl ether gas was introduced into the system three times, then the pressure of the autoclave was maintained at 3.0 MPa, and the temperature was raised to 180°C for 20 h. The temperature of the autoclave was lowered to room temperature, the pressure was reduced to normal pressure, and the solvent was removed under negative pressure to obtain 70.6 g of 1-trimethylsiloxy-4-methoxycyclohexene crude product.

[0034] In a 500 mL four-necked flask, 350 mL of dichloromethane and 70.6 g of 1-trimethylsiloxy-4-methoxycyclohexene crude product were added, 2.14 g of 30% hydrochloric acid (0.05 eq) was added, and the temperature was raised to 40°C for 2 h. The reaction liquid was cooled to room temperature, 100 g of water was added, the lower organic phase was separated, dichloromethane was recovered under normal pressure, and 34.2 g of colorless oily liquid was obtained by negative pressure rectification, which was p-methoxycyclohexanone product with a purity of 98.5%, and the two-step mass yield was 75.9%.

[0035] 1H-NMR(CDCl3): δ3.65(s,1H),3.44(s,3H),2.66–2.54(m,2H),2.30(dt,2H),2.13(dq,2H),2.04–1.91(m,2H).

[0036] Example 2:

[0037] In a 500 mL autoclave, 250 mL of chlorobenzene and 50 g of 2-trimethylsiloxy-1,3-butadiene were added sequentially. After evacuating the autoclave and purging the system with vinyl methyl ether gas three times, the pressure in the autoclave was maintained at 2.5 MPa, and the temperature was raised to 200 °C for 20 h. The autoclave temperature was then lowered to room temperature, the pressure was reduced to atmospheric pressure, and the solvent was removed under negative pressure to obtain 71.3 g of crude 1-trimethylsiloxy-4-methoxycyclohexene.

[0038] In a 500 mL four-necked flask, 350 mL of dichloromethane and 71.3 g of the crude 1-trimethylsiloxy-4-methoxycyclohexene were added, along with 6.89 g of 10% sulfuric acid (0.02 eq). The mixture was heated to 40 °C and reacted for 3 h. The reaction solution was cooled to room temperature, washed with 150 g of water, and the lower organic phase was separated. The organic phase was first desolvated under normal pressure to recover dichloromethane, and then distilled under negative pressure to obtain 33.6 g of a colorless oily liquid, which was the p-methoxycyclohexanone product with a purity of 98.1% and a two-step yield of 74.6%.

[0039] 1 H-NMR(CDCl3): δ3.65(s,1H),3.44(s,3H),2.66–2.54(m,2H),2.30(dt,2H),2.13(dq,2H),2.04–1.91(m,2H).

[0040] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A method for synthesizing p-methoxycyclohexanone, characterized in that, Includes the following steps: (1) Vinyl methyl ether reacts with 2-trimethylsiloxy-1,3-butadiene to generate 1-trimethylsiloxy-4-methoxycyclohexene; (2) 1-Trimethylsiloxy-4-methoxycyclohexene is acidified to generate p-methoxycyclohexanone; The specific reaction formula is as follows:

2. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (1) is 0.5 MPa to 5.0 MPa.

3. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (1) is 150℃~200℃.

4. The synthesis method according to claim 1, characterized in that, The reaction solvent in step (1) is one or more of xylene, mixed xylene, and chlorobenzene.

5. The synthesis method according to claim 1, characterized in that, The acids used in step (2) are hydrochloric acid, sulfuric acid, and phosphoric acid.

6. The synthesis method according to claim 1, characterized in that, In step (2), the molar ratio of 1-trimethylsiloxy-4-methoxycyclohexene to acid is 1:0.01 to 0.

1.

7. The synthesis method according to claim 4, characterized in that, In step (1), the mass-volume ratio of 2-trimethylsiloxy-1,3-butadiene to solvent is 1:4-5.

8. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (2) is 30℃~40℃.

9. The synthesis method according to claim 1, characterized in that, The concentration of acid in step (2) is 10% to 30%.

10. The synthesis method according to claim 1, characterized in that, The reaction solvent in step (2) is one or more of dichloromethane and 1,2-dichloroethane.

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