CN109912455B - Method for preparing 4-hydroxy-4' -cyanobiphenyl - Google Patents
Method for preparing 4-hydroxy-4' -cyanobiphenyl Download PDFInfo
- Publication number
- CN109912455B CN109912455B CN201910250252.2A CN201910250252A CN109912455B CN 109912455 B CN109912455 B CN 109912455B CN 201910250252 A CN201910250252 A CN 201910250252A CN 109912455 B CN109912455 B CN 109912455B
- Authority
- CN
- China
- Prior art keywords
- hydroxy
- cyanobiphenyl
- preparing
- bromophenol
- reagent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A method for preparing 4-hydroxy-4 '-cyanobiphenyl belongs to the technical field of organic synthetic chemistry, p-bromophenol is used as a raw material, substituted boric acid is prepared firstly, and then the substituted boric acid is prepared into the 4-hydroxy-4' -cyanobiphenyl
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, relates to preparation of a liquid crystal intermediate, and particularly relates to a method for preparing 4-hydroxy-4' -cyanobiphenyl.
Background
PDLC is an abbreviation for Polymer Dispersed Liquid Crystal, English, known in Chinese as Polymer Dispersed Liquid Crystal. The Polymer Dispersed Liquid Crystal (PDLC) is prepared by mixing low molecular liquid crystal (liquid crystal, abbreviated as LC) with prepolymer Kuer UV65 glue, performing polymerization reaction under certain conditions to form micron-sized liquid crystal droplets, uniformly dispersing the liquid crystal droplets in a polymer network, and obtaining a material with electro-optic response characteristics by using dielectric anisotropy of liquid crystal molecules, wherein the material mainly works between a scattering state and a transparent state and has certain gray scale. The polymer dispersed liquid crystal film is a film material with excellent comprehensive performance obtained by combining liquid crystal and a polymer. The liquid crystal molecules endow the polymer dispersed liquid crystal film with remarkable electro-optic characteristics, so that the polymer dispersed liquid crystal film is widely concerned and has wide application prospect. Compared with the traditional display device, the polymer dispersion type liquid crystal display has many advantages, such as no need of a polarizing plate and an orientation layer, simple preparation process, and easy preparation of a large-area flexible display and the like. The liquid crystal display device is widely applied to optical modulators, thermosensitive and pressure-sensitive devices, electric control glass, light valves, projection display, electronic books and the like.
Common liquid crystal molecules in PDLC comprise alkyl biphenyl nitrile and alkoxy biphenyl nitrile with smaller delta n and lower clearing point; also, alkyl terphenylnitriles or alkyl cyclohexyl biphenylnitriles of relatively large Δ n and relatively high clearing points; and high clearing point and good solubilityEsters as pesticidesA monomer.
Wherein 4-hydroxy-4' -cyanobiphenyl (hydroxy biphenyl nitrile for short) is an important intermediate, which can be used for preparing alkoxy biphenyl nitrile and partial ester monomers, such as:
and also has important application in the preparation of other liquid crystal materials, such as 4-hydroxy-4' -bibenzoic acid
It is used to prepare a large class of alkoxy biphenyl formate liquid crystal
A key intermediate of (1).
Hydroxybiphenylnitriles are generally prepared in the current preparation process as 4-biphenols
The preparation method is as follows:
the method A comprises the following steps: after the 4-diphenol is subjected to the friedel-crafts acylation of trichloro-acetyl chloride, the 4-diphenol reacts with ammonia to form amide, and then thionyl chloride is dehydrated to form nitrile to obtain a product, wherein the yield is 51.9% -56.7%.
The method B comprises the following steps: the protection of the hydroxyl group of 4-biphenol by acetic anhydride was carried out in a similar manner to that of Process 1, wherein the protecting group was removed in the amide-forming step, in a yield of 47.7%.
The method C comprises the following steps: biphenyl is used as a raw material, firstly is subjected to a friedel-crafts acylation and tandem bromination reaction with acetyl chloride to obtain p-bromodiphenylethanone, then is subjected to Bayer-Virgige oxidation rearrangement to obtain 4' -bromo-4-diphenol, and finally is subjected to a reaction with cuprous cyanide to obtain a product, wherein the yield is 33%.
With the development of coupling reaction technology in recent years, there has been developed a method of synthesizing by a coupling means, for example,
appl Organometal chem.2017; in e3778, p-iodophenol and p-cyanobenzene boronic acid are used for coupling to obtain 4-hydroxy-4' -cyanobiphenyl in one step, the reaction time is 24 hours, but the yield is only 76%, and the raw materials are expensive and not easy to obtain.
WO2006072015A2 discloses that p-bromophenol and p-cyanobenzene boronic acid are used for coupling to obtain 4-hydroxy-4' -cyanobiphenyl in one step, high-activity ligand tri-tert-butylphosphine is used, the reaction time is 48 hours, and the yield is only 55%.
In WO2016008561A1, p-methoxyphenylboronic acid and p-bromobenzonitrile are coupled and demethylated to obtain 4-hydroxy-4' -cyanobiphenyl, although the raw materials are relatively easy to obtain, the demethylation conditions are complex and ultralow temperature of-78 ℃ is required.
Bioorganic & Medicinal Chemistry 11(2003) 3457-3474, p-bromophenol was protected with a silicon reagent, then subjected to lithium halide exchange, boronization, hydrolysis, and coupling with p-bromophenylnitrile (yield: 100% × 65% × 91% ═ 59%). The method has low total yield, expensive organic lithium reagent, harsh reaction conditions and relatively high price of p-bromobenzonitrile, and is not suitable for industrial production.
The methods all have obvious defects, such as long steps, low yield, large discharge amount of three wastes and lower than 60 percent of comprehensive yield in the conventional method. Although the coupling method is simple in process, the raw materials used are not readily available, and the total yield from the initial starting material p-bromophenol is also around 60% in view of the synthesis of raw materials such as p-hydroxyphenylboronic acid, p-cyanophenylboronic acid and the like.
Disclosure of Invention
The invention aims to provide a simple, high-efficiency and convenient method for industrially producing 4-hydroxy-4' -cyanobiphenyl.
The technical scheme adopted by the invention for realizing the purpose is as follows:
a method for preparing 4-hydroxy-4 '-cyanobiphenyl comprises the steps of firstly preparing boronic acid by taking p-bromophenol as a raw material, and then preparing 4-hydroxy-4' -cyanobiphenyl
Performing Suzuki coupling reaction on the substituted boric acid and p-chlorobenzonitrile in the presence of a solvent, alkali and a catalyst by using PG as a protective group, deprotecting to obtain 4-hydroxy-4' -cyanobiphenyl, and controlling the molar ratio of p-bromophenol to p-chlorobenzonitrile to alkali to be 1.0 (1.0-1.5) to (2.0-4.0) and the temperature of Suzuki coupling reaction to be 50-120 ℃.
The mass ratio of the catalyst to the p-bromophenol is (0.00001-0.02): 1.
The preparation of the boronic acid comprises the following steps:
A. p-bromophenol reacts with a protecting group reagent under the action of a solvent and an acid-binding agent to obtain hydroxyl-protected p-bromophenol
PG represents a protecting group;
B. adding the hydroxyl protected p-bromophenol obtained in the step A into magnesium chips to generate GrignardReacting the reagent with a boric acid ester reagent, and hydrolyzing to obtain the substituted boric acid
PG represents a protecting group.
In the step A, the molar ratio of p-bromophenol to protecting group reagent and acid-binding agent is 1.0: (1.0-2.0): (1.0-2.5).
In the step B, the molar ratio of the p-bromophenol to the magnesium chips to the boric acid ester is 1.0: (1.0-2.0): (1.2-2.5).
In the step A, the reaction temperature is controlled to be-10-50 ℃.
In the step B, the reaction temperature of the reaction of the Grignard reagent and the borate reagent is controlled to be-15-80 ℃.
In the step A, the solvent is one or a combination of more of xylene, toluene, benzene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and ethylene glycol dimethyl ether; the protective group reagent is one or a combination of more of dihydropyran, trimethylchlorosilane, tert-butyldimethylchlorosilane, phenyldimethylchlorosilane and triisopropylchlorosilane; the acid-binding agent is one or a combination of more of triethylamine, pyridine, imidazole, tetramethylethylenediamine, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
In the step B, the borate reagent is one or a combination of more of trimethyl borate, triethyl borate, triisopropyl borate and tributyl borate. Step B is also carried out under the condition of a solvent, and the solvent is one or a combination of more of dimethylbenzene, methylbenzene, benzene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and glycol dimethyl ether; during hydrolysis, hydrochloric acid, sulfuric acid, phosphoric acid or formic acid, acetic acid, ammonium chloride, ammonium phosphate, ammonium sulfate and ammonium bromide with the concentration of less than 1mol/L are added for hydrolysis.
In the Suzuki coupling reaction, a solvent is one or a combination of more of dimethylbenzene, methylbenzene, benzene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and ethylene glycol dimethyl ether; the alkali is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium fluoride and potassium fluoride; the catalyst is a combination of equivalent palladium catalyst and ligand, wherein the palladium catalyst is one or a combination of more of tetrakis (triphenylphosphine) palladium, palladium chloride, palladium acetate and bis (triphenylphosphine) palladium dichloride, and the ligand is one or a combination of more of X-Phos, S-Phos, tri-tert-butylphosphine, di (1-adamantyl) butylphosphine and tricyclohexylphosphine.
The invention has the beneficial effects that:
1. the preparation of p-hydroxybenzeneboronic acid (or phenylboronic acid protected by a protective group) basically takes p-bromobenzonitrile as a raw material, the yield in the prior art is very low (30-60%), and the invention directly uses the p-hydroxybenzeneboronic acid in the reaction without separation by selecting a designed solvent, thereby reducing the loss in the treatment process. The p-bromobenzonitrile is a fine chemical, has small market capacity, high price, complex production process and large discharge of three wastes, and the p-chlorobenzonitrile is a medical pesticide dye intermediate, has wide source and low price.
2. The invention also aims at the reaction conditions to carry out long-term research, simplifies the reaction process, and can simplify the production process to at least two reaction kettles in commercial production. And the total yield of p-bromophenol can reach more than 85! The production efficiency and the discharge amount of three wastes are far superior to the prior production technology.
3. In the invention, p-bromophenol is dissolved in a solvent in a first reaction vessel, an acid-binding agent and a protecting group reagent are added, after the reaction is finished, water is added for quenching and dissolving generated salt, and after a water layer is separated, an organic layer is a solution of p-bromophenol with protected phenolic hydroxyl groups. Adding magnesium chips and a solvent into a second reaction container, then dropwise adding a solution of p-bromophenol with protected phenolic hydroxyl groups to prepare a Grignard reagent, adding borate, then carrying out weak acid hydrolysis, and removing a water layer, wherein an organic layer is a p-hydroxyphenylboronic acid solution with protected phenolic hydroxyl groups. Then, without changing a container, adding parachlorobenzonitrile, an alkali solution and a catalyst, heating to generate a coupling reaction, and simultaneously completing the deprotection group. The product 4-hydroxy-4' -cyanobiphenyl is obtained through post-treatment and is white crystal.
4. The invention has the advantages that the added solvent runs through the whole reaction process, and the process does not need separation and purification, thereby reducing the loss in the separation process, having simple process and small discharge amount of three wastes. Overcomes the defects of the prior method, improves the prior method of Suzuki cross-coupling reaction, obtains the product simply and efficiently, and is convenient for industrial production.
Detailed Description
The invention provides a simple and efficient method suitable for industrial production of 4-hydroxy-4' -cyanobiphenyl, aiming at solving various defects in the prior art. The preparation process is completed in the same main organic solvent system by using p-bromophenol as material and through phenolic hydroxyl group protection, Grignard reaction, boronization, hydrolysis, coupling and deprotection. The present invention will be further described with reference to the following examples.
Example 1
A500 ml three-necked bottle reaction device is assembled, 34.6g (0.2mol) of p-bromophenol and 19.75g (0.25mol) of pyridine are placed in a three-necked bottle, 100ml of 2-methyltetrahydrofuran is added, the temperature of an ice-water bath is controlled to be less than 10 ℃, 25.92g (0.24mol) of 50ml of 2-methyltetrahydrofuran solution is dropwise added under the protection of nitrogen, the temperature is controlled to be not more than 20 ℃, the temperature is controlled to be 15-20 ℃, the reaction is stopped after 2 hours of reaction, 50ml of saturated salt water multiplied by 2 is used for washing the reaction solution, and 10g of anhydrous magnesium sulfate is dried for standby application.
Adding 5.76g (0.24mol) of magnesium chips into a 1000ml three-neck flask, carrying out water bath at 30 ℃, dropwise adding the p-trimethylsiloxy bromobenzene 2-methyltetrahydrofuran solution prepared in the previous step, initiating the preparation of a Grignard reagent, continuously controlling the temperature to be 30-35 ℃ after dropwise adding, reacting for 2 hours, cooling an ice salt bath to-15 ℃, dropwise adding 41.6g (0.4mol) of trimethyl borate 100ml 2-methyltetrahydrofuran solution, controlling the temperature to be not more than 0 ℃, naturally heating to 20 ℃ after dropwise adding, hydrolyzing with 21.4g (0.4mol) of saturated ammonium chloride aqueous solution (50ml of water), standing, separating, removing a water phase, adding 30.25g (0.22mol) of p-chlorobenzonitrile, 11.6g (0.2mol) of potassium fluoride, 50ml of water, 0.02g of tetrakis (triphenylphosphine palladium), and X-phos0.02g into an organic phase, heating to 50 ℃, reacting for 8 hours, cooling to a normal temperature, preparing hydrochloric acid with 50ml of 30% concentrated hydrochloric acid and 50ml of water, carrying out hydrolysis, heating back flow for 1 hour, separating liquid while the solution is hot, and discarding the water phase. The organic phase is concentrated and crystallized to obtain a white-like product, namely the hydroxybiphenyl nitrile 33.18g, the purity is 99.72 percent, and the total yield is 85.1 percent.
Example 2 (Industrial Scale)
Cleaning a 500L reaction kettle device and drying, placing 34.6kg of p-bromophenol and 20.19kg of dihydropyran in the reaction kettle, adding 100L of dimethylbenzene, controlling the temperature of refrigerating fluid to be less than-10 ℃, dropwise adding 50L of dimethylbenzene solution of 25.92kg of trimethylchlorosilane under the protection of nitrogen, controlling the temperature to be less than 0 ℃, stopping the reaction after the dropwise adding is finished, controlling the temperature of a refrigerating fluid system to be-5 ℃, reacting for 4 hours, and drying 10kg of anhydrous magnesium sulfate for later use, wherein 50L multiplied by 2 of saturated salt water is used for washing the reaction solution.
Adding 5.76kg of magnesium chips into another dry 1000L reaction kettle, heating to 30 ℃, dropwise adding the p-trimethylsiloxy bromobenzene xylene solution prepared in the previous step to initiate preparation of a Grignard reagent, continuously controlling the temperature to 30-35 ℃ after dropwise adding, reacting for 4 hours, cooling the frozen liquid to-10 ℃, dropwise adding 100L xylene solution of trimethyl borate 41.6kg, controlling the temperature to be not more than 0 ℃, naturally heating to 20 ℃ after dropwise adding, hydrolyzing with 21.4kg of saturated ammonium chloride (50L water), standing, separating liquid, removing the water phase, adding 30.25kg of p-chlorobenzonitrile, 27.6kg of potassium carbonate, 50L of water, 20g of tetrakis (triphenylphosphine palladium) and X-Phos20g into the organic phase, heating to 120 ℃, reacting for 12 hours, cooling to normal temperature, preparing dilute hydrochloric acid by using 50L of 30% concentrated hydrochloric acid and 50L of water, hydrolyzing, heating to 100 ℃, reacting for 2 hours, separating liquid while the liquid is hot, and discarding the water phase. The organic phase is concentrated and crystallized to obtain 33.4kg of off-white product hydroxyl biphenyl nitrile, the purity is 99.68 percent, and the total yield is 85.64 percent.
Example 3 (Industrial Scale)
Cleaning a 500L reaction kettle device and drying, placing 34.6kg of p-bromophenol and 17kg of imidazole in a reaction kettle, adding 100L of dioxane, controlling the temperature of a refrigerating fluid to be less than 20 ℃, dropwise adding 46.08kg of 50L of dioxane solution of triisopropyl chlorosilane under the protection of nitrogen, controlling the temperature to be less than 30 ℃, controlling the temperature to be 15-25 ℃ in a water bath after dripping, stopping the reaction after reacting for 4 hours, washing the reaction solution with 50L multiplied by 2 of saturated salt water, and drying 10kg of anhydrous magnesium sulfate for later use.
Adding 6kg of magnesium chips into another dry 1000L reaction kettle, heating to 40 ℃, dropwise adding the prepared triisopropylsiloxy bromobenzene dioxane solution to initiate preparation of a Grignard reagent, continuously controlling the temperature to 50-60 ℃ after dropwise adding, reacting for 4 hours, cooling the freezing solution to 20 ℃, dropwise adding 100L dioxane solution of triisopropylborate 45.12kg, controlling the temperature to be not more than 30 ℃, heating to 80 ℃ after dropwise adding, reacting for 4 hours, hydrolyzing with 30% concentrated hydrochloric acid 50L, standing to remove a water phase, adding parachlorobenzonitrile 30.25kg, potassium carbonate 27.6kg, water 50L, palladium acetate 10g and tri-tert-butylphosphine 20g, heating to reflux, reacting for 12 hours, cooling to normal temperature, preparing into dilute hydrochloric acid with 30% concentrated hydrochloric acid 50L and water 50L, hydrolyzing, heating to reflux for 2 hours, thermally separating, and discarding the water phase. The organic phase is concentrated and crystallized to obtain a white-like product, namely 34.1kg of hydroxy biphenyl nitrile, the purity is 99.58 percent, and the total yield is 87.2 percent.
Example 4 (Industrial Scale)
Cleaning a 500L reaction kettle device and drying, placing 34.6kg of p-bromophenol and 12kg of sodium carbonate into the reaction kettle, adding 100L of toluene, controlling the temperature of refrigerating fluid to be less than 10 ℃, dropwise adding 25.92kg of 50L of toluene solution of trimethylchlorosilane under the protection of nitrogen, controlling the temperature to be not more than 20 ℃, stopping the reaction after dropwise adding, controlling the temperature to be 20-25 ℃ to react for 3 hours, washing the reaction solution with 50L multiplied by 2 saturated salt water, and drying 10kg of anhydrous magnesium sulfate for later use.
Adding 5.76kg of magnesium chips into another dry 1000L reaction kettle, heating to 30 ℃, dropwise adding the p-trimethylsiloxy bromobenzene toluene solution prepared in the previous step to initiate preparation of a Grignard reagent, continuously controlling the temperature to 35-40 ℃ after dropwise adding, reacting for 3 hours, cooling the frozen liquid to-15 ℃, dropwise adding 100L of toluene solution of trimethyl borate 41.6kg, controlling the temperature to be not more than 0 ℃, after dropwise adding, heating to 40 ℃, hydrolyzing with 21.4kg of saturated ammonium chloride (50L of water), standing, separating liquid, removing the water phase, adding 30.25kg of p-chlorobenzonitrile, 27.6kg of potassium carbonate, 50L of water, 1.73g of tetrakis (triphenylphosphine palladium) and 1.g of X-phos into the organic phase, heating to 7380 ℃, reacting for 10 hours, cooling to normal temperature, preparing dilute hydrochloric acid by using 50L of 30% concentrated hydrochloric acid and 50L of water, heating, refluxing for 1.5 hours, separating liquid while the liquid is hot, and discarding the water phase. The organic phase is concentrated and crystallized to obtain a white-like product, namely the hydroxybiphenyl nitrile 33.2kg, the purity is 99.62 percent, and the total yield is 85.13 percent.
Example 5 (Industrial Scale)
Cleaning a 2000L reaction kettle device and drying, placing 138.4kg of p-bromophenol and 65kg of imidazole in a reaction kettle, adding 400L of toluene, controlling the temperature of refrigerating fluid to be less than 10 ℃, dropwise adding 103.7kg of trimethylchlorosilane 200L of toluene solution under the protection of nitrogen, controlling the temperature to be less than 20 ℃, stopping the reaction after dropwise adding, controlling the temperature to be 20-25 ℃ to react for 3 hours, and drying the reaction solution by using 200L multiplied by 2 saturated salt water and 40kg of anhydrous magnesium sulfate for later use.
Adding 22.7kg of magnesium chips into another dry 3000L reaction kettle, heating to 30 ℃, dropwise adding the p-trimethylsiloxy bromobenzene toluene solution prepared in the previous step to initiate preparation of a Grignard reagent, controlling the temperature to 30-35 ℃ after dropwise adding, reacting for 3 hours, cooling the frozen liquid to-10 ℃, dropwise adding 400L of toluene solution of trimethyl borate 166.4kg, controlling the temperature to be not more than 0 ℃, heating to 20 ℃ after dropwise adding, controlling the temperature to 20-30 ℃, reacting for 5 hours, hydrolyzing with 85.6kg of saturated ammonium chloride (200L of water), standing, separating liquid to remove a water phase, adding 121kg of p-chlorobenzonitrile, 110.4kg of potassium carbonate, 200L of water, 1.384g of tetrakis (triphenylphosphine palladium) and 1.384g of bis (1-adamantyl) butylphosphine into an organic phase, heating to reflux, reacting for 10 hours, cooling to normal temperature, preparing diluted hydrochloric acid by using 200L of 30% concentrated hydrochloric acid and 200L of water, hydrolyzing for 1.5 hours, separating liquid while the solution is hot, and discarding the water phase. The organic phase is concentrated and crystallized to obtain 134.1kg of the off-white product of the hydroxybiphenyl nitrile, the purity is 99.71 percent, and the total yield is 85.96 percent.
Claims (9)
1. A method for preparing 4-hydroxy-4 '-cyanobiphenyl comprises the steps of firstly preparing boronic acid by taking p-bromophenol as a raw material, and then preparing 4-hydroxy-4' -cyanobiphenyl
Performing Suzuki coupling reaction on the substituted boric acid and p-chlorobenzonitrile in the presence of a solvent, alkali and a catalyst by using PG as a protective group, deprotecting to obtain 4-hydroxy-4' -cyanobiphenyl, and controlling the molar ratio of p-bromophenol to p-chlorobenzonitrile to alkali to be 1.0 (1.0-1.5) to (2.0-4.0), wherein the temperature of the Suzuki coupling reaction is 50-120 ℃;
the preparation of the boronic acid comprises the following steps:
A. p-bromophenol reacts with a protecting group reagent under the action of a solvent and an acid-binding agent to obtain hydroxyl-protected p-bromophenol
PG represents a protecting group;
B. adding the hydroxyl protected p-bromophenol obtained in the step A into magnesium chips to generate a Grignard reagent, reacting with a boronate reagent, and hydrolyzing to obtain the substituted boric acid
PG represents a protecting group.
2. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein the mass ratio of the catalyst to the p-bromophenol is (0.00001-0.02): 1.
3. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein in step a, the molar ratio of p-bromophenol to protecting group reagent and acid-binding agent is 1.0: (1.0-2.0): (1.0-2.5).
4. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein in step B, the molar ratio of p-bromophenol to magnesium turnings and borate reagent is 1.0: (1.0-2.0): (1.2-2.5).
5. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein the reaction temperature in step A is controlled to be-10 to 50 ℃.
6. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein in the step B, the reaction temperature of the Grignard reagent and the borate reagent is controlled to be-15 to 80 ℃.
7. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein in step a, the solvent is one or more of xylene, toluene, benzene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and ethylene glycol dimethyl ether; the protective group reagent is one or a combination of more of dihydropyran, trimethylchlorosilane, tert-butyldimethylchlorosilane, phenyldimethylchlorosilane and triisopropylchlorosilane; the acid-binding agent is one or a combination of more of triethylamine, pyridine, imidazole, tetramethylethylenediamine, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
8. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein in step B, the borate reagent is one or a combination of trimethyl borate, triethyl borate, triisopropyl borate and tributyl borate.
9. The method for preparing 4-hydroxy-4' -cyanobiphenyl according to claim 1, wherein the solvent is one or a combination of xylene, toluene, benzene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane and ethylene glycol dimethyl ether; the alkali is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium fluoride and potassium fluoride; the catalyst is a combination of equivalent palladium catalyst and ligand, wherein the palladium catalyst is one or a combination of more of tetrakis (triphenylphosphine) palladium, palladium chloride, palladium acetate and bis (triphenylphosphine) palladium dichloride, and the ligand is one or a combination of more of X-Phos, S-Phos, tri-tert-butylphosphine, di (1-adamantyl) butylphosphine and tricyclohexylphosphine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910250252.2A CN109912455B (en) | 2019-03-29 | 2019-03-29 | Method for preparing 4-hydroxy-4' -cyanobiphenyl |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910250252.2A CN109912455B (en) | 2019-03-29 | 2019-03-29 | Method for preparing 4-hydroxy-4' -cyanobiphenyl |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109912455A CN109912455A (en) | 2019-06-21 |
| CN109912455B true CN109912455B (en) | 2022-03-01 |
Family
ID=66967709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910250252.2A Active CN109912455B (en) | 2019-03-29 | 2019-03-29 | Method for preparing 4-hydroxy-4' -cyanobiphenyl |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109912455B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110016028A (en) * | 2019-04-17 | 2019-07-16 | 上海大学 | Naphthyridine dipyrrole compound and preparation method thereof |
| CN114262263B (en) * | 2021-12-28 | 2024-04-19 | 河北美星化工有限公司 | Preparation method of 4-iodophenol |
| CN116426295A (en) * | 2022-11-23 | 2023-07-14 | 河北凡克新材料有限公司 | Preparation method of side fluorine-containing terphenyl liquid crystal monomer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100548948C (en) * | 2002-12-09 | 2009-10-14 | 麻省理工学院 | The metal catalytic method of metal ligand and improvement based on this |
-
2019
- 2019-03-29 CN CN201910250252.2A patent/CN109912455B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100548948C (en) * | 2002-12-09 | 2009-10-14 | 麻省理工学院 | The metal catalytic method of metal ligand and improvement based on this |
Non-Patent Citations (5)
| Title |
|---|
| ERβ Ligands. Part 1: The Discovery of ERβ Selective Ligands which Embrace the 4-Hydroxy-biphenyl Template;Richard J. Edsall等;《Bioorganic & Medicinal Chemistry》;20031231;第3457–3474页 * |
| General synthesis and catalytic applications of Di(1-adamantyl)alkylphosphines and their phosphonium salts;Tewari, Amit 等;《Synthesis》;20040323;第935-941页 * |
| Palladium on carbon as a precatalyst for the Suzuki–Miyuara cross-coupling of aryl chlorides;J. P. Simeone,，J. R. Sowa;《Tetrahedron》;20071006;第63卷;第12646-12654页 * |
| Richard J. Edsall等.ERβ Ligands. Part 1: The Discovery of ERβ Selective Ligands which Embrace the 4-Hydroxy-biphenyl Template.《Bioorganic & Medicinal Chemistry》.2003,第3457–3474页. * |
| 叔丁基二甲硅氧基苯硼酸及羟基苯硼酸的制备;晁建平等;《有机化学》;20061231;第26卷(第7期);第1004-1007页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109912455A (en) | 2019-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109912455B (en) | Method for preparing 4-hydroxy-4' -cyanobiphenyl | |
| CN106883861B (en) | A kind of liquid crystal compound, composition and application thereof | |
| CN102924243B (en) | Liquid crystal compound containing cyclopentyl and difluorometheneoxy linking group, preparation method and applications thereof | |
| US20030203128A1 (en) | Fluorene derivatives and their polymers | |
| CN104119367A (en) | Preparation method of aryl boric acid | |
| CN109082280A (en) | A kind of preparation method of liquid crystal material | |
| CN107108488A (en) | Polymerizable compound and optically anisotropic body | |
| CN109423296A (en) | A kind of dibenzothiophenes class negative dielectric anisotropic compound and its preparation method and application | |
| CN109207160A (en) | A kind of liquid-crystal compounds of negative dielectric anisotropic and the preparation method and application thereof | |
| CN104004510A (en) | Organic luminescent material simultaneously having piezoluminescence and aggregation-induced luminescence properties, and synthesis method and application thereof | |
| CN109423297A (en) | A kind of dibenzothiophenes liquid-crystal compounds and its preparation method and application | |
| CN107267153B (en) | A kind of liquid crystal compound, composition and application thereof | |
| CN101928199B (en) | Divinyl liquid crystal compound and preparation method thereof | |
| CN101451065B (en) | Liquid crystal compound, liquid crystal display and optoelectronic device | |
| CN101503625B (en) | Preparation method of 1,2-diaryl ethine liquid crystal | |
| CN107400516A (en) | A kind of liquid-crystal compounds of cyclopropyl class negative dielectric anisotropic and its application | |
| CN103626724B (en) | A kind of compound containing tetrahydrofuran (THF), difluoro methylthio group class and its preparation method and application | |
| CN103788039B (en) | Liquid-crystal compounds containing oxinane difluoromethylenedioconnecting linking group and preparation method and application | |
| CN109207158A (en) | A kind of liquid-crystal compounds of the negative dielectric anisotropic containing alkenes and its application | |
| CN107628932A (en) | A kind of tolans diluent of fluorine-type containing side and its synthetic method for high birefringence rate liquid crystal | |
| CN107118781A (en) | A kind of synthetic method of liquid crystal media | |
| CN118561667B (en) | A method for preparing negative monomer liquid crystal containing ethane bridge bond | |
| CN108530275B (en) | Liquid crystal compound with negative dielectric anisotropy of 2, 3-difluorobenzene and preparation method and application thereof | |
| CN101565343B (en) | Preparation method of difluoro methoxy bridge bond compound | |
| CN107286291B (en) | A kind of highly polarized fluorescent film and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for preparing 4-hydroxy-4 '- cyano biphenyl Effective date of registration: 20220526 Granted publication date: 20220301 Pledgee: Ningxia East Guarantee Co.,Ltd. Pledgor: NINGXIA ZHONGXING DISPLAY MATERIALS Co.,Ltd. Registration number: Y2022640000009 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230809 Granted publication date: 20220301 Pledgee: Ningxia East Guarantee Co.,Ltd. Pledgor: NINGXIA ZHONGXING DISPLAY MATERIALS Co.,Ltd. Registration number: Y2022640000009 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |