阅读说明：本技术 一种乙烯基环己烷的制备方法 (Preparation method of vinyl cyclohexane ) 是由 刘洪强 杨忆 魏佳玉 朱克明 王松松 年成成 于 2020-12-26 设计创作，主要内容包括：本发明公开了一种乙烯基环己烷的制备方法,属于有机合成技术领域。以环己基甲酮为原料,首先与2,4,6-三异丙基苯磺酰肼缩合得到1-乙酰环己烷-2,4,6-三异丙基苯磺酰腙；随后在无机碱和非亲核强碱存在下反应得到乙烯基环己烷。该方法两步反应,路线简单,区域选择高,产品分离相对容易,产品蒸馏时需要加入一定量阻聚剂防止蒸馏过程中聚合。(The invention discloses a preparation method of vinyl cyclohexane, belonging to the technical field of organic synthesis. Taking cyclohexyl ketone as a raw material, firstly condensing the cyclohexyl ketone with 2,4, 6-triisopropylbenzenesulfonylhydrazide to obtain 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone; followed by reaction in the presence of an inorganic base and a strong non-nucleophilic base to give vinylcyclohexane. The method has two-step reaction, simple route, high area selection and relatively easy product separation, and a certain amount of polymerization inhibitor is required to be added during product distillation to prevent polymerization in the distillation process.)

1. The preparation method of vinyl cyclohexane is characterized by comprising the following reaction route:

the method comprises the following steps:

the first step is as follows: adding cyclohexyl ketone, 2,4, 6-triisopropylbenzenesulfonylhydrazide and pinacol into an alcohol solvent, heating for reflux reaction, and filtering to obtain 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone;

the second step is that: adding 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone into an organic solvent, reacting in the presence of inorganic base and non-nucleophilic strong base, adding sulfolane, heating, adding alcohol for quenching after the reaction is finished, and rectifying to obtain the vinylcyclohexane.

2. The process for producing vinylcyclohexane according to claim 1, wherein: in the first step of reaction, the alcohol solvent is selected from methanol or ethanol, and the alcohol solvent is separated out from the solution after the reaction is finished, and is directly filtered to obtain the 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone.

3. The process for producing vinylcyclohexane according to claim 1, wherein: in the first step of reaction, the molar ratio of the cyclohexyl ketone to the 2,4, 6-triisopropyl sulfonyl hydrazide is 1: 1-1.05.

4. The process for producing vinylcyclohexane according to claim 1, wherein: in the second step of reaction, the organic solvent is selected from tetrahydrofuran or 2-methyltetrahydrofuran, and a polymerization inhibitor is added in the distillation process.

5. The process for producing vinylcyclohexane according to claim 1, wherein: in the second step of reaction, the inorganic base is selected from NaH and CH₃ONa、C₂H₅ONa, t-BuOK or t-BuONa.

6. The process for producing vinylcyclohexane according to claim 1, wherein: in the second step of the reaction, the non-nucleophilic strong base is selected from LiHMDS, NaHMDS or LDA.

7. The process for producing vinylcyclohexane according to claim 1, wherein: in the second step of reaction, the molar ratio of the 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone to the inorganic base to the non-nucleophilic strong base is 1: 1-1.2: 1.0-1.2.

Technical Field

The invention relates to a preparation method of vinyl cyclohexane, belonging to the technical field of organic synthesis.

Background

Vinylcyclohexane, english name: vinylcyclohexane, CAS: 695-12-5, vinyl cyclohexane as a terminal olefin reagent is widely used in medicine, material, and polymer polymerization fields, and as a main skeleton structure, the vinyl cyclohexane has a very wide application value and is widely concerned. The vinyl cyclohexane and the oligodiol are synthesized into the surface active crown ether, and the vinyl cyclohexane can be used for obtaining the block copolymer of the vinyl cyclohexane through polymerization, and the like.

Heretofore, various methods for synthesizing vinylcyclohexane have been reported, among which [ Catalysis,2016,6, 666-.

Wherein [ Journal of organic Chemistry,1982,47,1983-1984] cyclohexanone with low price is used as raw material, and the synthetic route is as follows:

in this route, t-butyllithium chemicals, which are dangerous and highly flammable, are used, and therefore, they are not industrially scalable.

However, in the above synthetic route, there are problems that the industrial production is not suitable, such as the reaction conditions are severe, and it is necessary to deeply study the synthesis process of vinylcyclohexane, provide a reaction route which is superior, easily available in raw materials, safe and stable, and meet the industrial production to meet the increasing market demand.

Disclosure of Invention

In order to overcome the technical defects, the invention discloses a preparation method of vinylcyclohexane. Taking cyclohexyl ketone as a raw material, firstly condensing the cyclohexyl ketone with 2,4, 6-triisopropylbenzenesulfonylhydrazide to obtain 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone; followed by reaction in the presence of an inorganic base and a strong non-nucleophilic base to give vinylcyclohexane. The method has two steps of reaction, simple steps, high area selection and relatively easy product separation, and a certain amount of polymerization inhibitor is required to be added during product distillation to prevent polymerization in the distillation process.

The invention relates to a preparation method of vinyl cyclohexane, which comprises the following steps: firstly, adding cyclohexyl ketone, 2,4, 6-triisopropylbenzenesulfonylhydrazide and pinacol into an alcohol solvent, heating for reflux reaction, and filtering to obtain 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone; secondly, adding 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone into an organic solvent, reacting in the presence of inorganic base and non-nucleophilic strong base, adding sulfolane, heating, adding alcohol for quenching, and rectifying to obtain the vinylcyclohexane. The reaction equation is expressed as follows:

further, in the above technical scheme, the alcohol solvent in the first step is selected from methanol or ethanol, preferably ethanol. Water generated in the reaction process is combined with pinacol to form crystal water, and the reaction time is greatly shortened. After the reaction is finished, the product is separated out from the solution and is directly filtered to obtain the 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone. The pinacol crystal water is dissolved in the mother liquor alcohol solvent.

Further, in the technical scheme, the molar ratio of the cyclohexyl ketone to the 2,4, 6-triisopropyl sulfonyl hydrazide in the first step is 1: 1-1.05.

Further, in the above technical scheme, the organic solvent in the second step is selected from tetrahydrofuran or 2-methyltetrahydrofuran, and a polymerization inhibitor is added in the distillation process. The polymerization inhibitor is selected from 1, 4-hydroquinone or 2, 6-di-tert-butyl-4-methylphenol.

Further, in the above technical scheme, the inorganic base in the second step is selected from NaH and CH₃ONa、C₂H₅ONa, t-BuOK or t-BuONa.

Further, in the above technical solution, the non-nucleophilic strong base in the second step is selected from LiHMDS, NaHMDS or LDA.

Further, in the above technical scheme, the molar ratio of the 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone, the inorganic base and the non-nucleophilic strong base in the second step is 1: 1-1.2: 1.0-1.2.

In the experimental process, when p-toluenesulfonyl hydrazide is used for replacing 2,4, 6-triisopropylbenzenesulfonyl hydrazide, after the reaction is finished, a byproduct toluene and vinyl cyclohexane are subjected to azeotropic distillation, the boiling points of the toluene and the vinyl cyclohexane are close to each other, and the rectification, separation and purification are difficult.

Advantageous effects of the invention

The method is completed in two steps, the pinacol is added to absorb water in the first step, the reaction time is obviously shortened, and after the reaction is finished, the intermediate pure product can be obtained by direct filtration. And in the second step, inorganic base and non-nucleophilic base are combined to react, the regional selection is high, the reaction is finished, the product and the byproduct 2,4, 6-triisopropylbenzene are relatively easy to separate, sulfolane is added to play a role of a bottom-filling solvent, and a certain amount of polymerization inhibitor is required to be added during product distillation and placed for metamorphic polymerization in the distillation process.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The invention is further illustrated by the following specific examples. These examples are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. After reading the description of the invention, one skilled in the art can make various changes and modifications to the invention, and such equivalent changes and modifications also fall into the scope of the invention defined by the claims.

Example 1

Into a reaction flask, 25.2g of cyclohexyl ketone (0.2mol), 200mL of methanol and 11.8g of pinacol (0.1mol) were charged, and a mixed solution of 59.7g of 2,4, 6-triisopropylbenzenesulfonylhydrazine (0.2mol) and methanol (100mL) was added dropwise at 30-35 ℃. After the dropwise addition, the temperature is raised and the reflux reaction is carried out for 1 hour, the temperature is reduced to 0 ℃, and the filtration is carried out. Leaching the filter cake with methanol and n-heptane, and drying to obtain 75.5g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone, wherein the yield is as follows: 92.8%, HPLC: 99.3 percent.¹H NMR(400MHz,CDCl₃):8.11(s,1H),7.12-7.08(m,2H),3.13-3.07(m,3H),2.89(s,4H),2.41(s,3H),1.54-1.50(m,4H),1.42-1.39(m,2H),1.29-1.21(m,18H).

Example 2

Into a reaction flask, 25.2g of cyclohexyl ketone (0.2mol), 450mL of ethanol, 11.8g of pinacol (0.1mol) and 59.7g of 2,4, 6-triisopropylbenzenesulfonylhydrazine (0.20mol) were charged, and after the charging, the mixture was stirred uniformly. Heating to reflux reaction for 3 hr, detecting by TLC until no raw material remains, cooling to 0 deg.C, and filtering. Leaching the filter cake with ethanol and n-heptane, and drying to obtain 79.8g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone, wherein the yield is as follows: 98.0%, HPLC: 98.8 percent.

Example 3

40.7g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone (0.10mol) and 200mL of tetrahydrofuran were put into a reaction flask under a nitrogen atmosphere, and after stirring the mixture uniformly, 11.2g of potassium tert-butoxide (0.10mol) was added thereto and the mixture was stirred at room temperature for 2 hours. Then the temperature is reduced to-20 ℃, 110mL of 1.0mol/L lithium hexamethyldisilazide (0.11 mol)/tetrahydrofuran mixed solution is dripped, and the temperature is slowly raised to 0 ℃ after the dripping is finished to react overnight. Then, 15mL of sulfolane and 0.5g of 2, 6-di-tert-butyl-4-methylphenol were added, and the temperature was raised to 40 to 50 ℃ to react for 3 hours. Adding 4mL of anhydrous methanol for quenching, distilling under normal pressure to remove the solvent, and continuously heating and rectifying to obtain 9.0g of colorless transparent liquid vinylcyclohexane, wherein the yield is as follows: 81.7%, GC: 99.0 percent. Adding 0.01 percent of product weight polymerization inhibitor, and placing in a freezer for freezing and storing.¹H NMR(400MHz,CDCl₃):5.78(m,1H),4.91(dd,J＝18.9,J＝10.8Hz,2H),1.95(m,1H),1.75-1.64(m,5H),1.29-1.06(m,5H).

Example 4

40.7g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone (0.10mol) and 300mL of tetrahydrofuran were put into a reaction flask under nitrogen protection, and after stirring the mixture uniformly, 9.6g of sodium tert-butoxide (0.10mol) was added thereto, and the mixture was stirred at room temperature for 2 hours. Then the temperature is reduced to-20 ℃, 60mL of mixed solution of 2.0mol/L sodium hexamethyldisilazane (0.12 mol)/tetrahydrofuran is dripped, and after the dripping is finished, the temperature is slowly raised to 0 ℃ for reaction overnight. Then, 15mL of sulfolane and 0.5g of 2, 6-di-tert-butyl-4-methylphenol were added, and the temperature was raised to 40 to 50 ℃ to react for 5 hours. Adding 4mL of anhydrous methanol for quenching, distilling under normal pressure to remove the solvent, and continuously heating and rectifying to obtain 8.5g of colorless transparent liquid vinylcyclohexane, wherein the yield is as follows: 77.1%, GC: 99.2 percent.

Example 5

40.7g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone (0.10mol) and 250mL of 2-methyltetrahydrofuran were put into a reaction flask under a nitrogen atmosphere, and after stirring the mixture uniformly, 5.4g of sodium methoxide (0.10mol) was added and the mixture was stirred at room temperature for 2 hours. Then, the temperature is reduced to-20 ℃, 110mL of 1.0mol/L lithium hexamethyldisilazide (0.11 mol)/2-methyltetrahydrofuran mixed solution is dripped, after the dripping is finished, the temperature is slowly raised to 0 ℃ for reaction overnight, then 12mL of sulfolane and 0.4g of 1, 4-hydroquinone are added, the temperature is raised to 40-50 ℃ for reaction for 3 hours. Adding 4mL of anhydrous methanol for quenching, distilling under normal pressure to remove the solvent, and continuously heating and rectifying to obtain 8.1g of colorless transparent liquid vinylcyclohexane, wherein the yield is as follows: 73.6%, GC: 99.3 percent.

Example 6

Under the protection of nitrogen, 40.7g of 1-acetylcyclohexane-2, 4, 6-triisopropylbenzenesulfonylhydrazone (0.10mol) and 300mL of tetrahydrofuran are put into a reaction bottle, stirred uniformly, cooled to 0 ℃, added with 4.0g of 60% sodium hydride (0.10mol) in batches, and kept warm and stirred for reaction for 30 minutes. Then the temperature is reduced to-20 ℃, 60mL of 2.0mol/L lithium diisopropylamide (0.12 mol)/tetrahydrofuran solution is dripped, and after the dripping is finished, the temperature is slowly raised to 0 ℃ for reaction overnight. Then, 12mL of sulfolane and 0.5g of 2, 6-di-tert-butyl-4-methylphenol were added, and the temperature was raised to 40 to 50 ℃ to react for 3 hours. Adding 4mL of anhydrous methanol for quenching, distilling under normal pressure to remove the solvent, and continuously heating and rectifying to obtain 7.7g of colorless transparent liquid vinyl cyclohexane, wherein the yield is as follows: 69.7%, GC: 99.1 percent.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical solutions and the inventive concepts of the present invention within the technical scope of the present invention.