WO2024040754A1 - Method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane - Google Patents

Abstract

The present invention relates to the technical field of organic synthesis, and provides a method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane. According to the present invention, N-sulfonylhydrazone and phosphine salt are taken as raw materials, cis-2-methyl-7-octadecene can be obtained by a one-step method under the action of an organic base, and the generation of trans-2-methyl-7-octadecene can be avoided. The yield and the purity of the cis-2-methyl-7-octadecene obtained in the present invention are both high, the yield of the cis-2-methyl-7-octadecene is 68-96%, and the purity of the cis-2-methyl-7-octadecene is higher than 98.8%. Because the cis-2-methyl-7-octadecene has high purity, the yield and the purity of the cis-7,8-epoxy-2-methyloctadecane obtained in the present invention are both high, the yield of the cis-7,8-epoxy-2-methyloctadecane is higher than 90%, and the purity of the cis-7,8-epoxy-2-methyloctadecane is higher than 99%.

Description

A kind of synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane

This application is required to be submitted to the China Patent Office on August 24, 2022. The application number is CN202211016165.9, and the invention name is "A cis-2-methyl-7-octadecene and cis-7,8-epoxy" -2-Methyloctadecane Synthesis Method", the entire content of which is incorporated into this application by reference.

Technical field

The invention relates to the technical field of organic synthesis, and in particular to a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane.

Background technique

In 1970, Bierl and other researchers isolated and identified the structure of the gypsy moth sex pheromone from the female adults of the gypsy moth as (+)-(7R,8S)-7,8-epoxy-2-methyloctadecane. Since then, many researchers in the chemical and biological fields have devoted themselves to the synthesis of high optical purity gypsy moth sex pheromones.

In actual monitoring of the gypsy moth situation and trapping of adult insects, the racemic gypsy moth sex pheromone, cis-7,8-epoxy-2-methyloctadecane, is often used. Therefore, the key intermediate cis- 2-Methyl-7-octadecene is used as raw material, and the target product cis-7,8-epoxy-2-methyloctadecane is synthesized through epoxidation reaction.

The key intermediate cis-2-methyl-7-octadecene is usually made of 2-methyl-7-octadecyne as the raw material, and is hydrogenated in the cis form under the action of Lindler catalyst, or using a highly hindered boron reagent. Reduction is obtained (Chemistry of Natural Compounds 1983,19,593; J.Chem.Ecolo.1983,9(2),211.).

However, this method always produces trans-2-methyl-7-octadecene during the reaction process, and the purity of the obtained cis-2-methyl-7-octadecene is low, making the final product cis-7,8 -The yield and purity of epoxy-2-methyloctadecane is low.

Contents of the invention

In view of this, the object of the present invention is to provide a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane. The synthesis method of cis-2-methyl-7-octadecene provided by the invention can avoid the generation of trans-2-methyl-7-octadecene, thereby improving the synthesis of cis-7,8-epoxy-2 -Yield and purity of methyloctadecane.

In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:

Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;

In formula a, Ar is an aromatic group;

Preferably, the Ar is phenyl, p-methylphenyl, p-cumylphenyl, p-tert-butylphenyl, o-methylphenyl, o-cumylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.

Preferably, the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, and hexamethyldisilamine Lithium hexamethyldisilamide, sodium hexamethyldisilazide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, isopropylmagnesium bromide and phenylmagnesium bromide one or several kinds.

Preferably, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is 1:1 to 1.2.

Preferably, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is 1:1 to 1.2.

Preferably, the temperature of the substitution reaction is -80~-30°C and the time is 4~6 hours.

The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:

Synthesize cis-2-methyl-7-octadecene according to the above method;

Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.

Preferably, the peroxyacid is one or more selected from the group consisting of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.

Preferably, the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is 1:1.2-1.8.

Preferably, the temperature of the cyclization reaction is -10 to 30°C, and the time is 1 to 5 hours.

The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps: under the action of an organic base, an N-sulfonylhydrazone compound with a structure shown in formula a and a compound with formula b The phosphine salt compound with the structure shown undergoes a substitution reaction to obtain cis-2-methyl-7-octadecene. The invention uses N-sulfonyl hydrazone and phosphonium salt as raw materials, and under the action of organic base, can obtain cis-2-methyl-7-octadecene in one step, and can avoid trans-2-methyl-7 -Generation of octadecene. The yield and purity of cis-2-methyl-7-octadecene obtained by the present invention are both relatively high. Among them, the yield of cis-2-methyl-7-octadecene is 68 to 96%, and the purity is higher than 98.8%. At the same time, the raw materials used in the synthesis method of the present invention are easily available and the cost is low. It has the advantages of short synthesis route, simple operation, convenient product separation and purification, wide applicability of reaction substrates, etc., and is suitable for industrial mass production.

The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane. First, cis-2-methyl-7-octadecane is synthesized according to the above method, and then the peroxyacid Under the action of , cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane. Since cis-2-methyl-7-octadecane has higher purity, the yield and purity of cis-7,8-epoxy-2-methyloctadecane obtained in the present invention are relatively high, among which cis-7,8-epoxy-2-methyloctadecane has higher purity. The yield of formula-7,8-epoxy-2-methyloctadecane is higher than 90%, and the purity is higher than 99%. At the same time, the synthesis method provided by the invention is simple to operate, low in cost, and suitable for industrial mass production.

Description of drawings

Figure 1 shows the synthetic route of cis-7,8-epoxy-2-methyloctadecane;

Figure 2 is the carbon spectrum NMR spectrum of cis-7,8-epoxy-2-methyloctadecane obtained in Example 1.

Detailed ways

The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:

Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;

In formula a, Ar is an aromatic group;

In the present invention, the Ar is preferably phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butyl Phenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.

In the present invention, the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, hexamethyldimethyl Lithium silamide, sodium hexamethyldisilamide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, isopropylmagnesium bromide and phenyl bromide One or more types of magnesium.

In the present invention, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is preferably 1:1 to 1.2, more preferably 1:1.1.

In the present invention, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is preferably 1:1 to 1.2, more preferably 1:1.1.

In the present invention, the organic solvent used in the substitution reaction is preferably one of toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether and ethylene glycol dimethyl ether, or Several kinds. In the present invention, the substitution reaction is preferably carried out under a protective atmosphere, and the protective atmosphere is preferably argon.

In the present invention, the preferred mixing method is: first mix the phosphonium salt compound having the structure represented by formula b with an organic base and an organic solvent, and then add the N-sulfonylhydrazone compound having the structure represented by formula a.

In the present invention, the temperature of the substitution reaction is preferably -80 to -30°C, more preferably -80 to -60°C; the time is preferably 4 to 6 hours, more preferably 5 hours.

In the present invention, after the substitution reaction, the present invention preferably performs post-treatment on the obtained substitution reaction liquid, and the post-treatment preferably includes the following steps:

Mix the substitution reaction liquid with water to quench the reaction to obtain a quenched reaction liquid;

The organic solvent of the quenched reaction solution is removed, the remaining liquid is mixed with petroleum ether, and solid-liquid separation, washing, drying and concentration are performed in sequence. The obtained concentrate is purified by column chromatography to obtain cis-2-methyl-7- Pure octadecene.

In the present invention, the solid-liquid separation method is preferably suction filtration; the washing detergent is preferably salt water; the drying is preferably desiccant drying, and the desiccant is preferably sodium sulfate. The present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.

In the present invention, the stationary phase used for column chromatography purification is preferably silver nitrate-loaded 400 mesh silica gel; the mobile phase is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably 150: 1.

The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:

Synthesize cis-2-methyl-7-octadecene according to the above method;

Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.

In the present invention, the synthesis method of cis-2-methyl-7-octadecene is the same as above and will not be described again.

In the present invention, under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.

In the present invention, the peroxyacid is preferably one or more of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.

In the present invention, the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is preferably 1:1.2-1.8, more preferably 1:1.4-1.6.

In the present invention, the organic solvent used in the cyclization reaction is preferably toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1,2 -One or more of dichloroethane, chloroform and methylene chloride.

In the present invention, the temperature of the cyclization reaction is preferably -10~30°C, more preferably 0~10°C; the time is preferably 1~5h, more preferably 2~4h.

After the cyclization reaction, the present invention preferably performs post-processing on the obtained cyclization reaction liquid, and the post-processing preferably includes the following steps:

Add saturated sodium thiosulfate solution to the cyclization reaction solution to quench the reaction to obtain a quenched reaction solution;

Separate the quenched reaction solution to obtain an aqueous phase and an organic phase;

The organic phase was washed, dried, concentrated and purified by column chromatography in sequence to obtain pure cis-7,8-epoxy-2-methyloctadecane.

In the present invention, the detergent used for washing is preferably a sodium carbonate aqueous solution, and the number of washings is preferably 2 times. In the present invention, the drying is preferably drying with a desiccant, and the desiccant is preferably sodium sulfate. The present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.

In the present invention, the stationary phase for column chromatography purification is preferably 200 mesh silica gel, the mobile phase is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably 20:1.

In the present invention, the synthetic route of cis-7,8-epoxy-2-methyloctadecane is shown in Figure 1.

The synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane provided by the present invention will be described in detail below in conjunction with the examples. They should be understood as limitations on the scope of protection of the present invention.

Example 1

Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ;Add N-phenylsulfonylhydrazone (3.3g, 10mmol), continue to stir and react at -80°C for 4 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, concentrate to remove the solvent, and add petroleum ether (80 mL) was stirred for 30 minutes, suction filtered, the filtrate was washed with brine, dried over sodium sulfate, concentrated, and the residue was purified by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2 -Methyl-7-octadecene 2.3g (yield 86%, gas phase purity 98.6%).

¹ H NMR (400MHz, CDCl ₃ ): δ0.76-1.02(m,9H), 1.14-1.61(m,23H), 1.89-2.16(m,4H), 5.38(m,2H).

Dissolve cis-2-methyl-7-octadecene (2.3g, 8.6mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (3.2g, 15.5 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 2.24g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 92%, gas phase purity 99.1%).

¹ H NMR (400MHz, CDCl ₃ ): δ0.86-0.92 (m, 9H), 1.14-1.59 (m, 27H), 2.85-2.96 (m, 2H); ¹³ C NMR (100MHz, CDCl ₃ ): δ14 .1,22.58,22.67,22.69,26.60,26.86,27.32,27.83,27.87,27.89,29.32,29.56,29.59,31.90,38.91,57.17; HRMS(ESI)calcd for C19H38NaO ⁺ [M+Na ⁺ ]305.28 20,found305 .2825.

The carbon NMR spectrum of the obtained cis-7,8-epoxy-2-methyloctadecane is shown in Figure 2.

Example 2

Under argon protection, add phosphine salt (5.5g, 12mmol) and methyltetrahydrofuran (80mL) into the reaction bottle, cool to -60°C, slowly inject lithium diisopropylamide solution (6mL, 2M), and stir for 0.5 hours; add N-2-naphthylsulfonylhydrazone (3.8g, 10mmol), continue to stir and react at -60°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove the solvent. Add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2-methyl-7-octadecene 1.9g (yield 71%, gas phase purity 98.6%).

Dissolve cis-2-methyl-7-octadecene (1.9g, 7.1mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (2.6g, 12.8 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 1.83g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 91%, gas phase purity 99.2%), ¹ of the product The HNMR, ¹³ C NMR and HRMS detection data are consistent with Example 1.

Example 3

Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) into the reaction bottle, cool to -70°C, slowly inject lithium hexamethyldisilazide tetrahydrofuran solution (10mL, 1.5M), and stir 1 hour; add N-p-tert-butylbenzenesulfonylhydrazone (3.8g, 10mmol), continue to stir and react at -70°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate Remove the solvent, add petroleum ether (80 mL) and stir for 30 minutes, filter with suction, wash the filtrate with brine, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate = 150: 1) Obtain 2.0 g of cis-2-methyl-7-octadecene (yield 75%, gas phase purity 99.5%).

Dissolve cis-2-methyl-7-octadecene (2.0g, 7.5mmol) in 1,2-dichloroethane (100mL), cool to 0°C, and add m-chloroperoxybenzoic acid ( 3.1g, 15mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and column the residue Chromatography purification (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) gave cis-7,8-epoxy-2-methyloctadecane 2.1g (yield 96%, gas phase purity 99.8%), The ¹ HNMR, ¹³ C NMR and HRMS detection data of the product are consistent with Example 1.

Example 4

Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ; Add N-2,4,6-trimethylbenzenesulfonylhydrazone (3.7g, 10mmol), continue to stir and react at -80°C for 6 hours, then naturally warm to room temperature and react for 4 hours; add water (5mL) dropwise to extract. Reaction, concentrate to remove the solvent, add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate =150:1) to obtain 1.82g of cis-2-methyl-7-octadecene (yield 68%, gas phase purity 98.8%).

Dissolve cis-2-methyl-7-octadecene (1.82g, 6.8mmol) in chloroform (50mL), cool to 0°C, and add m-chloroperoxybenzoic acid (2.22g, 10.9mmol, 85 % content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and the residue will be purified by column chromatography (200 mesh) Silica gel, petroleum ether: ethyl acetate = 20:1) to obtain 1.81g of cis-7,8-epoxy-2-methyloctadecane (yield 94%, gas phase purity 99.5%), ¹ HNMR of the product, ¹³ C NMR and HRMS detection data are consistent with Example 1.

Example 5

Under argon protection, add phosphine salt (5.5g, 12mmol) and methyltetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir 1 hour; add N-2-chlorobenzenesulfonylhydrazone (3.6g, 10mmol), continue to stir and react at -80°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove Solvent, add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate = 150:1 ) to obtain 2.56 g of cis-2-methyl-7-octadecene (yield 96%, gas phase purity 99.6%).

Dissolve cis-2-methyl-7-octadecene (2.56g, 9.6mmol) in chloroform (100mL), cool to -5°C, and add m-chloroperoxybenzoic acid (2.93g, 14.4mmol, in 10 batches). 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and the residue will be purified by column chromatography (200 silica gel, petroleum ether: ethyl acetate = 20:1) to obtain cis-7,8-epoxy-2-methyloctadecane 2.58g (yield 95%, gas phase purity 99.4%), ¹ HNMR of the product, ^{The 13} C NMR and HRMS detection data are consistent with Example 1.

Example 6

Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ; Add N-p-toluenesulfonylhydrazone (3.4g, 10mmol), continue to stir and react at -80°C for 4 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove the solvent. Add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2-methyl-7-octadecene 2.19g (yield 82%, gas phase purity 98.9%).

Dissolve cis-2-methyl-7-octadecene (2.19g, 8.2mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (3.0g, 14.8 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 2.21g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 95%, gas phase purity 99.6%), ¹ of the product The HNMR, ¹³ C NMR and HRMS detection data are consistent with Example 1.

The above are only preferred embodiments of the present invention. It should be noted that those skilled in the art can make several improvements and modifications without departing from the principles of the present invention. These improvements and modifications can also be made. should be regarded as the protection scope of the present invention.

Claims (16)

1. A synthetic method of cis-2-methyl-7-octadecene, including the following steps:

   Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;

   

   In formula a, Ar is an aromatic group;

   
2. The synthesis method according to claim 1, wherein Ar is phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl phenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4, 6-Trimethylphenyl.
3. The synthesis method according to claim 1 or 2, characterized in that the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, dimethoxide, Lithium isopropylamide, lithium hexamethyldisilamide, sodium hexamethyldisilamide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, One or more of isopropyl magnesium bromide and phenyl magnesium bromide.
4. The synthesis method according to claim 1, characterized in that the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is 1:1 to 1.2.
5. The synthesis method according to claim 1 or 4, characterized in that the molar ratio of the N-sulfonylhydrazone compound having the structure shown in formula a to the organic base is 1:1 to 1.2.
6. The synthetic method according to claim 1, characterized in that the organic solvent used in the substitution reaction is toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether and ethylene glycol One or more of dimethyl ether.
7. The synthesis method according to claim 1 or 4, characterized in that the temperature of the substitution reaction is -80~-30°C and the time is 4~6h.
8. The synthesis method according to claim 1, characterized in that, after the substitution reaction, the obtained substitution reaction liquid is subjected to post-processing, and the post-processing includes the following steps:

   Mix the substitution reaction liquid with water to quench the reaction to obtain a quenched reaction liquid;

   The organic solvent of the quenched reaction solution is removed, the remaining liquid is mixed with petroleum ether, and solid-liquid separation, washing, drying and concentration are performed in sequence. The obtained concentrate is purified by column chromatography to obtain cis-2-methyl-7- Pure octadecene.
9. The synthesis method according to claim 8, wherein the stationary phase used for column chromatography purification is silver nitrate-loaded 400 mesh silica gel; the mobile phase is petroleum ether and ethyl acetate, and the petroleum ether and ethyl acetate are The volume ratio is 150:1.
10. A synthesis method of cis-7,8-epoxy-2-methyloctadecane, including the following steps:

    Synthesize cis-2-methyl-7-octadecene according to the method described in any one of claims 1 to 9;

    Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
11. The synthesis method according to claim 10, wherein the peroxyacid is one or more of peroxyformic acid, peracetic acid, perbenzoic acid and meta-chloroperoxybenzoic acid.
12. The synthesis method according to claim 10, characterized in that the molar ratio of the cis-2-methyl-7-octadecene and peroxyacid is 1:1.2~1.8.
13. The synthetic method according to claim 10, characterized in that the organic solvent used in the cyclization reaction is toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol One or more of glycol dimethyl ether, 1,2-dichloroethane, chloroform and methylene chloride.
14. The synthesis method according to claim 10 or 12, characterized in that the temperature of the cyclization reaction is -10~30°C and the time is 1~5h.
15. The synthesis method according to claim 10, characterized in that, after the cyclization reaction, the obtained cyclization reaction liquid is post-processed, and the post-processing includes the following steps:

    Add saturated sodium thiosulfate solution to the cyclization reaction solution to quench the reaction to obtain a quenched reaction solution;

    Separate the quenched reaction solution to obtain an aqueous phase and an organic phase;

    The organic phase was washed, dried, concentrated and purified by column chromatography in sequence to obtain pure cis-7,8-epoxy-2-methyloctadecane.
16. The synthetic method according to claim 15, characterized in that the stationary phase purified by column chromatography is 200 mesh silica gel, the mobile phase is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether and ethyl acetate is 20:1.

Images