阅读说明：本技术 反-4’-(4-烷基苯基)（1,1’-联环己烷）-4-酮的合成方法 (Synthesis method of trans-4 '- (4-alkyl phenyl) (1, 1' -dicyclohexyl) -4-ketone ) 是由 巨妮娟 段迎春 蔡文刚 张鸿宝 高仁孝 于 2019-11-14 设计创作，主要内容包括：本发明公开了一种反-4’-(4-烷基苯基)(1,1’-联环己烷)-4-酮的合成方法,属于液晶中间体合成方法技术领域,包括以下步骤：以对烷基卤代苯为起始原料,经格氏偶联、脱水脱保护、加氢、转型制得反-4’-(4-烷基苯基)(1,1’-联环己烷)-4-酮；本发明化合物制备方法简单,反应条件温和,将传统的脱水、脱保护两步反应合并为一步,达到缩短路线、简化后处理、节约工时成本的目的；本发明合并反应步骤、缩短路线、简化操作、降低废水,适合工业化生产。(The invention discloses a method for synthesizing trans-4 '- (4-alkyl phenyl) (1, 1' -dicyclohexyl) -4-ketone, belonging to the technical field of liquid crystal intermediate synthesis methods and comprising the following steps: taking alkyl halogenated benzene as a starting material, and preparing trans-4 '- (4-alkyl phenyl) (1, 1' -bicyclohexyl) -4-ketone by Grignard coupling, dehydration deprotection, hydrogenation and transformation; the compound disclosed by the invention is simple in preparation method and mild in reaction conditions, and combines two traditional reactions of dehydration and deprotection into one step, so that the purposes of shortening the route, simplifying the post-treatment and saving the working time and cost are achieved; the invention combines reaction steps, shortens the route, simplifies the operation, reduces the waste water and is suitable for industrial production.)

1. A method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-ketone, which is characterized by comprising the following steps:

s1: 4-alkyl halogenated benzene and magnesium powder are subjected to Grignard reaction, and then dicyclohexyl ethylene glycol monoketal is added to react to generate a mixture containing a compound shown as a formula (II), wherein the reaction formula is as follows:

s2: adding acid into the mixture containing the compound of the formula (II) in S1 to carry out dehydration deprotection reaction to generate the compound of the formula (III), wherein the reaction formula is as follows:

the molar ratio of the acid to the biscyclohexanone ethylene glycol monoketal is 5-15:1, and the acid is hydrochloric acid, sulfuric acid, formic acid or acetic acid;

s3: hydrogenating the compound of the formula (III) under the action of a catalyst to generate a compound of the formula (IV), wherein the reaction formula is as follows:

s4: the compound of formula (IV) is transformed to produce the compound of formula (I), i.e. trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one, according to the following reaction equation:

2. the method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one according to claim 1, wherein the mixture of S1 containing the compound of formula (II) is prepared by the following steps:

dissolving magnesium powder and 4-alkyl halogenated benzene in a solvent I, adding iodine at the temperature of 30-80 ℃, reacting for 0-5h, adding a dicyclohexyl ethylene glycol monoketal/solvent II solution at the temperature of 10-70 ℃, keeping the temperature at 10-70 ℃, and reacting for 1-5h to prepare a mixture containing a compound of a formula (II);

the molar ratio of the magnesium powder to the 4-alkyl halogenated benzene is 1.1-2:1, the mass ratio of the magnesium powder to the iodine is 880-2180:1, the dosage ratio of the solvent I to the 4-alkyl halogenated benzene is 2.5-10mL:1g, the molar ratio of the biscyclohexanone ethylene glycol monoketal to the 4-alkyl halogenated benzene is 1.1-2:1, and the dosage ratio of the solvent II to the biscyclohexanone ethylene glycol monoketal is 2-10mL:1 g.

3. The process of claim 2, wherein solvent I is diethyl ether or tetrahydrofuran and solvent II is tetrahydrofuran, diethyl ether or toluene.

4. The method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one according to claim 1, wherein the compound of formula (III) in S2 is prepared by the following steps:

adding acid serving as a dehydration deprotection reagent into the mixture which is prepared by S1 and contains all the compounds of the formula (II), reacting for 1-5h at the temperature of 20-60 ℃, extracting, washing with water, and distilling to prepare compounds of the formula (III);

the molar ratio of the acid to the biscyclohexanone ethylene glycol monoketal is 5-15: 1; the acid is hydrochloric acid, sulfuric acid, formic acid or acetic acid.

5. The method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one according to claim 1, wherein the compound of formula (IV) S3 is prepared by the following steps:

dissolving a compound shown in a formula (III) in a solvent III, adding a catalyst, carrying out hydrogenation reaction for 5-20h under the conditions of 0.1-3MPa and 20-60 ℃ in a hydrogen environment, filtering and concentrating to dryness to obtain a compound shown in a formula (IV);

the dosage ratio of the solvent III to the compound of the formula (III) is 3-10mL:1 g; the mass ratio of the catalyst to the compound of formula (III) is 0.01-0.1: 1.

6. The process of claim 5, wherein the reaction solvent III is ethanol, toluene or tetrahydrofuran.

7. The process for the synthesis of trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one according to claim 1, wherein the compound of formula (i) is prepared by:

dissolving a compound shown in a formula (IV) in a solvent IV, adding potassium tert-butoxide, reacting for 2-10h at 20-70 ℃ under the protection of nitrogen, extracting, washing with water, filtering and recrystallizing to obtain a compound shown in a formula (I);

the molar ratio of the potassium tert-butoxide to the compound shown in the formula (IV) is 0.3-2:1, and the dosage ratio of the solvent IV to the compound shown in the formula (IV) is 3-15mL:1 g.

8. The process of claim 7, wherein the solvent iv is dimethyl sulfoxide, N-dimethylformamide or N-methylpyrrolidone.

Technical Field

The invention belongs to the technical field of liquid crystal intermediate synthesis methods, and particularly relates to a synthesis method of trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-ketone.

Background

Trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one as an indispensable intermediate for the liquid crystalline monomer 1- [ (trans ) -4- (3-buten-1-yl) [1, 1-bicyclohexyl ] -4-yl ] -4-alkyl-benzene, patent JP2014162752, adopts the following synthetic route:

the synthesis route has many reaction steps, and is long, tedious in post-treatment and long in total process consumption, so that the time cost is overhigh; the four-step water washing process except the hydrogenation step results in much process waste water, and is not suitable for large-scale production at present with increasingly severe environmental protection situation.

Disclosure of Invention

In order to overcome the defects of more reaction steps, complicated post-treatment, long consumed time and more wastewater, the invention provides the synthesis method of trans-4 '- (4-alkylphenyl) (1, 1' -dicyclohexyl) -4-ketone, which has the advantages of shortening the process steps, simplifying the post-treatment operation, reducing the consumed time of the process, reducing the amount of wastewater and being suitable for large-scale industrial production.

The invention aims to provide a method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -dicyclohexyl) -4-ketone, which comprises the following steps:

s1: 4-alkyl halogenated benzene and magnesium powder are subjected to Grignard reaction, and then dicyclohexyl ethylene glycol monoketal is added to react to generate a mixture containing a compound shown as a formula (II), wherein the reaction formula is as follows:

s2: adding acid into the mixture containing the compound of the formula (II) in S1 to carry out dehydration deprotection reaction to generate the compound of the formula (III), wherein the reaction formula is as follows:

the molar ratio of the acid to the biscyclohexanone ethylene glycol monoketal is 5-15:1, and the acid is hydrochloric acid, sulfuric acid, formic acid or acetic acid;

s3: hydrogenating the compound of the formula (III) under the action of a catalyst to generate a compound of the formula (IV), wherein the reaction formula is as follows:

s4: the compound of formula (IV) is transformed to produce the compound of formula (I), i.e. trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one, according to the following reaction equation:

preferably, said mixture of S1 containing the compound of formula (ii) is prepared by:

dissolving magnesium powder and 4-alkyl halogenated benzene in a solvent I, adding iodine at the temperature of 30-80 ℃, reacting for 0-5h, adding a dicyclohexyl ethylene glycol monoketal/solvent II solution at the temperature of 10-70 ℃, keeping the temperature at 10-70 ℃, and reacting for 1-5h to prepare a mixture containing a compound of a formula (II);

the molar ratio of the magnesium powder to the 4-alkyl halogenated benzene is 1.1-2:1, the mass ratio of the magnesium powder to the iodine is 880-2180:1, the dosage ratio of the solvent I to the 4-alkyl halogenated benzene is 2.5-10mL:1g, the molar ratio of the biscyclohexanone ethylene glycol monoketal to the 4-alkyl halogenated benzene is 1.1-2:1, and the dosage ratio of the solvent II to the biscyclohexanone ethylene glycol monoketal is 2-10mL:1 g.

Preferably, the solvent I is diethyl ether or tetrahydrofuran, and the solvent II is tetrahydrofuran, diethyl ether or toluene.

Preferably, the compound of formula (iii) in S2 is specifically prepared by the following steps:

adding acid serving as a dehydration deprotection reagent into the mixture which is prepared by S1 and contains all the compounds shown in the formula (II), reacting for 1-5h at the temperature of 20-60 ℃, extracting, washing with water, and distilling to prepare the compounds shown in the formula (III);

the molar ratio of the acid to the biscyclohexanone ethylene glycol monoketal is 5-15: 1; the acid is hydrochloric acid, sulfuric acid, formic acid or acetic acid.

Preferably, the compound of formula (iv) of S3 is specifically prepared by the following steps:

dissolving a compound shown in a formula (III) in a solvent III, adding a catalyst, carrying out hydrogenation reaction for 5-20h under the conditions of 0.1-3MPa and 20-60 ℃ in a hydrogen environment, filtering and concentrating to dryness to obtain a compound shown in a formula (IV);

the dosage ratio of the solvent III to the compound of the formula (III) is 3-10mL:1 g; the mass ratio of the catalyst to the compound of formula (III) is 0.01-0.1: 1.

Preferably, the reaction solvent III is ethanol, toluene or tetrahydrofuran.

Preferably, the compound of formula (i) is prepared by:

dissolving a compound shown in a formula (IV) in a solvent IV, adding potassium tert-butoxide, reacting for 2-10h at 20-70 ℃ under the protection of nitrogen, extracting, washing with water, filtering and recrystallizing to obtain a compound shown in a formula (I);

the molar ratio of the potassium tert-butoxide to the compound shown in the formula (IV) is 0.3-2:1, and the dosage ratio of the solvent IV to the compound shown in the formula (IV) is 3-15mL:1 g.

Preferably, the solvent IV is dimethyl sulfoxide, N-dimethylformamide or N-methylpyrrolidone.

Compared with the prior art, the invention has the beneficial effects that:

(1) after the synthesis of the intermediate compound shown as the formula (II) of S1 is finished, no post-treatment operation is carried out, the reaction of the second step can be directly carried out, one-step post-treatment operation is saved, and the amount of wastewater is reduced;

(2) in S2, the traditional two-step reactions of dehydration and deprotection are combined into one step to be completed, so that one-step post-treatment washing operation is saved, the operation is simplified, and the reaction period is greatly shortened;

(3) selective hydrogenation of olefinic bond compounds containing ketone carbonyl functional groups is realized;

(4) large supply quantity of raw materials in the market, low price, high yield in each step, easy purification of products and low comprehensive cost.

Drawings

FIG. 1 is a mass spectrum of trans-4 '- (4-tolyl) (1, 1' -bicyclohexane) -4-one obtained in example 1;

FIG. 2 is an infrared plot of trans-4 '- (4-tolyl) (1, 1' -bicyclohexane) -4-one obtained in example 1;

FIG. 3 is a drawing showing the preparation of trans-4 '- (4-tolyl) (1, 1' -bicyclohexyl) -4-one from example 1¹H-NMR chart;

FIG. 4 is a drawing showing the preparation of trans-4 '- (4-tolyl) (1, 1' -bicyclohexyl) -4-one prepared in example 1¹³C-NMR chart.

Detailed Description

In order to make the technical solutions of the present invention better understood and implemented by those skilled in the art, the present invention is further described below with reference to the following specific embodiments and the accompanying drawings, but the embodiments are not meant to limit the present invention.

The invention provides a method for synthesizing trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-ketone, which comprises the following steps:

s1: 4-alkyl halogenated benzene and magnesium powder are subjected to Grignard reaction, and then dicyclohexyl ethylene glycol monoketal is added to react to generate a mixture containing a compound shown as a formula (II), wherein the reaction formula is as follows:

s2: adding acid into the mixture containing the compound of the formula (II) in S1 to carry out dehydration deprotection reaction to generate the compound of the formula (III), wherein the reaction formula is as follows:

the molar ratio of the acid to the biscyclohexanone ethylene glycol monoketal is 5-15:1, and the acid is hydrochloric acid, sulfuric acid, formic acid or acetic acid;

s3: hydrogenating the compound of the formula (III) under the action of a catalyst to generate a compound of the formula (IV), wherein the reaction formula is as follows:

s4: the compound of formula (IV) is transformed to produce the compound of formula (I), i.e. trans-4 '- (4-alkylphenyl) (1, 1' -bicyclohexyl) -4-one, according to the following reaction equation:

the synthesis method is specifically described below by way of example with reference to the preparation of trans-4 '- (4-tolyl) (1, 1' -bicyclohexyl) -4-one and examples 1 to 3.