Synthesis method of trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compound
阅读说明：本技术 一种反式-4-(4-烯基环己基)-1,1′-联苯类化合物的合成方法 (Synthesis method of trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compound ) 是由 刘海涛 郭强 葛炳辉 邹立伟 张博 马莹 王小伟 刘骞峰 于 2020-05-26 设计创作，主要内容包括：本发明公开了一种反式-4-(4-烯基环己基)-1,1’-联苯类化合物的合成方法,属于有机合成技术领域,包括以下步骤：以反式4-氯苯基环己烷甲酸作为原料,在还原剂下反应制得4-氯苯基环己烷甲醇；4-氯苯基环己烷甲醇与4-烷基苯硼酸在钯催化下,反应得到4-烷基联苯基环己烷甲醇；4-烷基联苯基环己烷甲醇在次氯酸钠、2,2,6,6-四甲基哌啶氮氧化物的氧化下,反应得到烷基联苯基环己烷甲醛；4-烷基联苯基环己烷甲醛与溴甲烷三苯基膦盐或溴乙烷三苯基膦盐制备成的Wittig试剂反应,在四氢呋喃溶液中,反应制得产物。本发明方法使用的原料便宜易得,步骤短,收率高,路线环保,有利于实现规模化的大生产。(The invention discloses a method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds, which belongs to the technical field of organic synthesis and comprises the following steps: trans-4-chlorophenyl cyclohexanecarboxylic acid is used as a raw material and reacts under a reducing agent to prepare 4-chlorophenyl cyclohexanemethanol; 4-chlorophenyl cyclohexane methanol and 4-alkyl benzene boric acid react under the catalysis of palladium to obtain 4-alkyl biphenyl cyclohexane methanol; 4-alkyl biphenyl cyclohexane methanol reacts under the oxidation of sodium hypochlorite and 2,2,6, 6-tetramethyl piperidine nitrogen oxide to obtain alkyl biphenyl cyclohexane formaldehyde; 4-alkyl biphenyl cyclohexane formaldehyde reacts with Wittig reagent prepared from bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt, and the product is prepared in tetrahydrofuran solution. The method has the advantages of cheap and easily-obtained raw materials, short steps, high yield, environment-friendly route and contribution to realizing large-scale production.)
1. A method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds is characterized by comprising the following steps:
s1, taking trans-4-chlorophenyl cyclohexanecarboxylic acid as a raw material, taking lithium aluminum hydride or sodium borohydride as a reducing agent, taking tetrahydrofuran or ethanol as a solvent, and reacting at the temperature of 55-75 ℃ for 4-6 h to obtain a product, namely 4-chlorophenyl cyclohexanemethanol;
s2, reacting 4-chlorophenyl cyclohexane methanol with 4-alkyl phenylboronic acid in DMF at 130-140 ℃ for 4-6 h under the action of palladium acetate and potassium carbonate to obtain 4-alkyl biphenyl cyclohexane methanol;
s3, reacting 4-alkyl biphenyl cyclohexane methanol in dichloromethane solution at 0-10 ℃ for 2-4 h under the oxidation of sodium hypochlorite and 2,2,6, 6-tetramethyl piperidine nitrogen oxide to obtain alkyl biphenyl cyclohexane formaldehyde;
s4, 4-alkyl biphenyl cyclohexane formaldehyde, potassium tert-butoxide and a Wittig reagent prepared from bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt react for 1-2 h at 0-10 ℃ in a tetrahydrofuran solution to obtain a compound of formula (1);
the synthetic route is as follows:
wherein R is1Is alkyl of 1-5 carbon atoms, R2Is H or methyl.
2. The method for synthesizing trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 1, wherein the molar ratio of lithium aluminum hydride to trans-4-chlorophenylcyclohexanecarboxylic acid in S1 is 1-1.2: 1.
3. The method for synthesizing trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 1, wherein the molar ratio of sodium borohydride to trans-4-chlorophenylcyclohexanecarboxylic acid in S1 is 2: 1.
4. The method for synthesizing the trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 2 or 3, wherein the mass ratio of the solvent to the trans-4-chlorophenylcyclohexanecarboxylic acid is 4-6: 1.
5. The method for synthesizing trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 1, wherein the molar ratio of 4-alkylphenylboronic acid to 4-chlorophenyl cyclohexanemethanol in S2 is 1-1.1: 1.
6. The method for synthesizing trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 5, wherein the molar ratio of palladium acetate to 4-chlorophenyl cyclohexanemethanol is 0.003-0.005: 1; the molar ratio of the potassium carbonate to the 4-chlorophenyl cyclohexane methanol is 1-1.5: 1; the mass ratio of DMF to 4-chlorophenyl cyclohexane methanol is 5-6: 1.
7. The method for synthesizing the trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 1, wherein in S3, the molar ratio of sodium hypochlorite to 4-alkylbiphenyl cyclohexane methanol is 1: 1; the molar ratio of the 2,2,6, 6-tetramethyl piperidine oxynitride to the 4-alkyl biphenyl cyclohexane methanol is 0.01-0.02: 1.
8. The method for synthesizing the trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 7, wherein the mass ratio of the dichloromethane to the 4-alkylbiphenyl cyclohexane methanol is 10-15: 1.
9. The synthesis method of the trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds according to claim 1, wherein in S4, the molar ratio of bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt to 4-alkyl biphenyl cyclohexane formaldehyde is 1.2-1.5: 1; the molar ratio of the potassium tert-butoxide to the 4-alkyl biphenyl cyclohexane formaldehyde is 1.2-1.5: 1.
10. The method for synthesizing the trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds according to claim 9, wherein the mass ratio of tetrahydrofuran to 4-alkylbiphenyl cyclohexane formaldehyde is 5-10: 1.
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds.
Background
A Thin Film Transistor Liquid Crystal Display (TFT-LCD), which is one of the most important Liquid Crystal displays, is widely used in the fields of notebook computers, Liquid Crystal televisions, mobile phones, etc., and the Liquid Crystal televisions are the mainstream of the market. The liquid crystal material is one of important photoelectronic materials for liquid crystal displays, and plays an important role in improving the performance of the liquid crystal displays. In order to satisfy the corresponding characteristics required by various liquid crystal display devices, liquid crystal materials are generally formed by mixing a plurality of liquid crystal compounds, which requires that the liquid crystal compounds have good intersolubility, particularly at low temperature. The common liquid crystal compounds at present mainly include biphenyl liquid crystals, ester liquid crystals, phenylcyclohexane liquid crystals, ethane liquid crystals, acetylene liquid crystals, fluorine-containing liquid crystals, dioxane liquid crystals, chiral liquid crystals, and the like. In the researches of patents (WO2019102859, JP6452019, CN107286956, CN107189791, CN107151557, WO 2015050035, JP2014162751, WO2013002224, WO2011122598) and the like, alkenyl cyclohexyl biphenyls are used in liquid crystal material compositions to solve the rotational viscosity of negative liquid crystals, thereby improving the response speed of liquid crystal displays. Trans-4- (4-alkenylcyclohexyl) -1,1' -biphenyl compounds are used in the patent formulas as a liquid crystal compound, and the construction of trans-cyclohexane groups is inevitably involved in the traditional synthetic method of the compounds, so that the synthetic steps are prolonged, and the product yield is influenced.
Disclosure of Invention
In order to solve the problems, the invention discloses a method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds.
A method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds comprises the following steps:
s1, taking trans-4-chlorophenyl cyclohexanecarboxylic acid as a raw material, taking lithium aluminum hydride or sodium borohydride as a reducing agent, taking tetrahydrofuran or ethanol as a solvent, and reacting at the temperature of 55-75 ℃ for 4-6 h to obtain a product, namely 4-chlorophenyl cyclohexanemethanol;
s2, reacting 4-chlorophenyl cyclohexane methanol with 4-alkyl phenylboronic acid in DMF at 130-140 ℃ for 4-6 h under the action of palladium acetate and potassium carbonate to obtain 4-alkyl biphenyl cyclohexane methanol;
s3, reacting 4-alkyl biphenyl cyclohexane methanol in dichloromethane solution at 0-10 ℃ for 2-4 h under the oxidation of sodium hypochlorite and 2,2,6, 6-tetramethyl piperidine oxynitride to obtain alkyl biphenyl cyclohexane formaldehyde;
s4, 4-alkyl biphenyl cyclohexane formaldehyde, potassium tert-butoxide and a Wittig reagent prepared from bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt react for 1-2 h at 0-10 ℃ in a tetrahydrofuran solution to obtain a compound of formula (1);
the synthetic route is as follows:
wherein R is1Is alkyl of 1-5 carbon atoms, R2Is H or methyl.
Preferably, in S1, the molar ratio of lithium aluminum hydride to trans-4-chlorophenyl cyclohexanecarboxylic acid is 1-1.2: 1.
Preferably, in S1, the molar ratio of sodium borohydride to trans 4-chlorophenyl cyclohexanecarboxylic acid is 2: 1.
More preferably, the mass ratio of the solvent to the trans-4-chlorophenyl cyclohexanecarboxylic acid is 4-6: 1.
Preferably, in S2, the molar ratio of the 4-alkylphenylboronic acid to the 4-chlorophenyl cyclohexanemethanol is 1-1.1: 1.
Further preferably, the molar ratio of the palladium acetate to the 4-chlorophenyl cyclohexane methanol is 0.003-0.005: 1; the molar ratio of the potassium carbonate to the 4-chlorophenyl cyclohexane methanol is 1-1.5: 1; the mass ratio of DMF to 4-chlorophenyl cyclohexane methanol is 5-6: 1.
Preferably, in S3, the molar ratio of sodium hypochlorite to 4-alkyl biphenyl cyclohexane methanol is 1: 1; the molar ratio of the 2,2,6, 6-tetramethyl piperidine oxynitride to the 4-alkyl biphenyl cyclohexane methanol is 0.01-0.02: 1.
Further preferably, the mass ratio of the dichloromethane to the 4-alkyl biphenyl cyclohexane methanol is 10-15: 1.
Preferably, in S4, the molar ratio of bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt to 4-alkyl biphenyl cyclohexane formaldehyde is 1.2-1.5: 1; the molar ratio of the potassium tert-butoxide to the 4-alkyl biphenyl cyclohexane formaldehyde is 1.2-1.5: 1.
Further preferably, the mass ratio of tetrahydrofuran to 4-alkyl biphenyl cyclohexane formaldehyde is 5-10: 1.
Compared with the prior art, the invention has the following beneficial effects:
the invention selects the trans-4-chlorophenyl cyclohexanecarboxylic acid with low price as the raw material, omits the trouble of cyclohexane conformational isomerization in the traditional liquid crystal synthetic route, simplifies the synthetic route, improves the atom utilization rate, and provides a new synthetic method for the compounds.
The invention provides a brand-new preparation method of trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds, which has the advantages of simple preparation process, mild reaction conditions and over 85 percent of total process yield and is suitable for industrial production.
Drawings
FIG. 1 is a MS diagram of trans-4-methyl-4 '- (4-propenylcyclohexyl) -1,1' -biphenyl prepared in example 1;
FIG. 2 is a MS diagram of trans-4-ethyl-4 '- (4-vinylcyclohexyl) -1,1' -biphenyl prepared in example 2;
FIG. 3 is an infrared spectrum of trans-4-methyl-4 '- (4-propenylcyclohexyl) -1,1' -biphenyl prepared in example 2;
FIG. 4 is a MS diagram of trans-4-ethyl-4 '- (4-propenylcyclohexyl) -1,1' -biphenyl prepared in example 3.
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 examples and the accompanying drawings, but the examples are not intended to limit the present invention.
The invention provides a method for synthesizing trans-4- (4-alkenyl cyclohexyl) -1,1' -biphenyl compounds, which comprises the following steps:
s1, taking trans-4-chlorophenyl cyclohexanecarboxylic acid as a raw material, taking lithium aluminum hydride or sodium borohydride as a reducing agent, and reacting in tetrahydrofuran or ethanol solution at the temperature of 55-75 ℃ for 4-6 h to obtain a product, namely 4-chlorophenyl cyclohexanemethanol;
s2, reacting 4-chlorophenyl cyclohexane methanol with 4-alkyl phenylboronic acid in DMF at 130-140 ℃ for 4-6 h under the action of palladium acetate and potassium carbonate to obtain 4-alkyl biphenyl cyclohexane methanol;
s3, reacting 4-alkyl biphenyl cyclohexane methanol in dichloromethane solution at 0-10 ℃ for 2-4 h under the oxidation of sodium hypochlorite and 2,2,6, 6-tetramethyl piperidine oxynitride to obtain alkyl biphenyl cyclohexane formaldehyde;
s4, 4-alkyl biphenyl cyclohexane formaldehyde, potassium tert-butoxide and a Wittig reagent prepared from bromomethane triphenylphosphine salt or bromoethane triphenylphosphine salt react for 1-2 h at 0-10 ℃ in a tetrahydrofuran solution to obtain a compound of formula (1);
the synthetic route is as follows:
wherein R is1Is alkyl of 1-5 carbon atoms, R2Is H or methyl.
The synthesis method is specifically described below by way of examples.