CN114671745B - Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction - Google Patents

Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction Download PDF

Info

Publication number
CN114671745B
CN114671745B CN202011553254.8A CN202011553254A CN114671745B CN 114671745 B CN114671745 B CN 114671745B CN 202011553254 A CN202011553254 A CN 202011553254A CN 114671745 B CN114671745 B CN 114671745B
Authority
CN
China
Prior art keywords
compound
formula
reaction
palladium
ring
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
Application number
CN202011553254.8A
Other languages
Chinese (zh)
Other versions
CN114671745A (en
Inventor
吴玉成
赵李亮
徐爽
叶守陈
宋晓龙
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangsu Hecheng Advanced Materials Co ltd
Original Assignee
Jiangsu Hecheng Advanced Materials Co ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Jiangsu Hecheng Advanced Materials Co ltd filed Critical Jiangsu Hecheng Advanced Materials Co ltd
Priority to CN202011553254.8A priority Critical patent/CN114671745B/en
Publication of CN114671745A publication Critical patent/CN114671745A/en
Application granted granted Critical
Publication of CN114671745B publication Critical patent/CN114671745B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
    • C07C37/18—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by condensation involving halogen atoms of halogenated compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

The invention discloses a green method for synthesizing a compound containing a biaryl structure through a Suzuki coupling reaction. Compared with the conventional anhydrous aprotic solvent, the organic solvent provided by the invention adopts the etherate of the dihydric alcohol, so that the generation of reaction byproducts can be effectively reduced, the reaction yield is higher, the product purity is higher, and the subsequent application of the product is not influenced; the product of the invention is easier to separate from the reaction system, thereby reducing the economic cost and the time cost of post-treatment; the solvent used in the invention has the characteristics of high flash point and no smell, so that the risk is lower, and the environment-friendly requirement is met; therefore, the method for synthesizing the compound containing the biaryl structure through the Suzuki coupling reaction is favorable for realizing industrial production and has extremely high industrial application value.

Description

Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction
Technical Field
The invention relates to the field of organic synthesis, in particular to a green method for synthesizing a compound containing a biaryl structure through a Suzuki coupling reaction.
Background
Suzuki coupling (also known as Suzuki-Miyaura coupling, or Suzuki reaction, or Suzuki-Miyaura reaction) is a newer class of cross-coupling reactions in which aryl or alkenyl boronic acids or esters cross-couple with chloro, bromo, iodo-aromatic hydrocarbons or olefins under the catalysis of zero-valent palladium complexes. The reaction is first reported in 1979 by the Lingmelin chapter, has wide application range in organic synthesis, has stronger substrate adaptability and functional group tolerance, and is commonly used for synthesizing derivatives of multiolefin, styrene and biphenyl, thereby being applied to synthesis of a plurality of natural products and organic materials.
In recent years, the development of liquid crystal display materials has been greatly advanced, and various liquid crystal materials have been widely developed, wherein a ring system is a skeleton of the display material, and a liquid crystal phase is impossible without the existence of the ring system. The ring system has a linear structure, while the ring system of practical value is predominantly a six-membered ring, including (but not limited to): benzene ring, pyrimidine ring, pyridine ring, dioxane ring, and the like.
In the preparation process of the liquid crystal material, it is very common to prepare a compound containing a biaryl structure by utilizing a Suzuki coupling reaction, for example, chinese patent application CN102307838A discloses that the biaryl structure is constructed by utilizing the Suzuki coupling reaction, however, the reaction yield can only reach about 70 percent, and the product is difficult to separate from a reaction solvent, and needs to be subjected to post-treatment by processes such as extraction and the like, so that the compound does not meet the high standard requirements of modern chemistry on environmental protection.
Therefore, there is a need to optimize and improve the method for synthesizing the compound containing the biaryl structure by the Suzuki coupling reaction, so as to develop a green method with higher reaction yield, more convenient post-treatment, more economy and environmental protection.
Disclosure of Invention
The invention aims to: in order to solve the problems of low reaction yield, complex post-treatment, high three wastes and the like in the method for synthesizing the compound containing the biaryl structure through the Suzuki coupling reaction in the prior art, the invention aims to provide a green method for synthesizing the compound containing the biaryl structure through the Suzuki coupling reaction.
The technical scheme is as follows: in order to achieve the above object, the present invention provides a method for synthesizing a biaryl structure-containing compound by a Suzuki coupling reaction, wherein the biaryl structure-containing compound is a compound of formula a:
wherein,
R 1 and R is 2 Each independently represents hydrogen, cyano, thiocyano, isothiocyano, nitro, amino, C 1 -C 4 Alkylamino, halogen, C 1 -C 12 Non-halogenated alkyl, or C 1 -C 12 Haloalkyl groups, and one or more of the alkyl groups-CH 2 -may each be independently replaced by-O-, -S-, -CO-, -CS-, -ch=ch-, or-c≡c-, wherein-O-and/or-S-are not directly connected;
each independently represents C 3 -C 10 Cycloalkyl, C 5 -C 9 Heterocyclyl, or C 6 -C 10 Aryl, said C 3 -C 10 Cycloalkyl, C 5 -C 9 Heterocyclyl, or C 6 -C 10 One or more-H in the aryl group is optionally substituted with 1,2 or 3 groups independently selected from cyano, thiocyano, isothiocyano, nitro, amino, halogen, C 1 -C 6 Non-halogenated alkyl or C 1 -C 6 Haloalkyl, C 1 -C 6 Non-haloalkoxy and C 1 -C 6 Substituents of haloalkoxy groups, and one or more of the alkyl groups-CH 2 -may each be independently replaced by-O-, -S-, -CO-, -CS-, -ch=ch-, or-c≡c-, wherein-O-and/or-S-are not directly connected;
each independently represents C 6 -C 10 Aryl, said C 6 -C 10 One or more-H in the aryl group is optionally substituted with 1,2 or 3 groups independently selected from cyano, thiocyano, isothiocyano, nitro, amino, halogen, C 1 -C 6 Non-halogenated alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Non-haloalkoxy and C 1 -C 6 Substituents of haloalkoxy groups, one or more of the alkyl groups being-CH 2 -can be replaced independently of one another by-O-, -S-, -CO-, -CS-, -ch=ch-or-c≡c-, wherein-O-and/or-S-are not directly linked, and said C 6 -C 10 One or more of the aryl groups-ch=can each independently be replaced by-n=and;
Z 1 and Z 2 Each independently represents a single bond, -O-, -S-, -CO-O-, -O-CO-, -CH 2 ) n -、-(CF 2 ) n -、-CH＝CH-、-CF＝CH-、-CH＝CF-、-CF＝CF-、-C≡C-、-CH 2 O-、-OCH 2 -、-CF 2 O-or-OCF 2 -；
a and b each independently represent an integer of 0 to 2;
the method is characterized by comprising the following steps:
the compound of formula I
With a compound of formula II in the presence of a base, a palladium catalyst, water and an organic solvent
Wherein,
x represents chlorine, bromine or iodine;
L 1 and L 2 Each independently represents a hydroxyl group, or, L 1 And L 2 Together form a bridging group-O- (C (R) a ) 2 ) q O-, wherein q is 2 or 3, R a Represents hydrogen or C 1 -C 3 An alkyl group;
R 1 、Z 1 、Z 2 a and b are as defined above; and is also provided with
The organic solvent is an etherate of a dihydric alcohol.
In some embodiments of the invention, the organic solvent is one or more compounds of formula M:
wherein,
r represents-H or C 1 -C 5 An alkyl group;
R x and R is y Each independently represents C 1 -C 5 An alkyl group; and is also provided with
n represents an integer of 1 to 8, wherein when n represents an integer of 3 to 8, and the structural fragmentContains one or more-CH 2 -at the time, the one or more-CH 2 -optionally each independently replaced by-O-, provided that-O-is not directly linked.
In some embodiments of the invention, R preferably represents-H or methyl, and R x And R is y Each independently represents C 1 -C 3 An alkyl group.
In some embodiments of the present invention, the organic solvent is further preferably one or more of diglyme, ethylene glycol dimethyl ether, diethylene glycol diethyl ether, ethylene glycol diethyl ether, dipropylene glycol dimethyl ether, dipropylene glycol diethyl ether, and dipropylene glycol diisopropyl ether; dipropylene glycol dimethyl ether is particularly preferred.
In the present invention, halogen means fluorine, bromine, chlorine or iodine, in particular fluorine, bromine or chlorine.
In the present invention, C 1 -C 12 Non-haloalkyl means a saturated straight or branched hydrocarbon radical containing from 1 to 12 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2-dimethylpropyl, 1-ethylpropyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-dimethylbutyl, 2, 3-dimethylbutyl, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 2-trimethylpropyl, 1, 2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl, and the like.
In the present invention, C 1 -C 12 Haloalkyl means a straight or branched alkyl group containing 1 to 12 carbon atoms, wherein one or more hydrogen atoms of these groups are replaced by halogen atoms as described above. C (C) 1 -C 12 Examples of haloalkyl are, for example, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-difluoroethyl, 2-trifluoroethyl, 2-chloro-2-fluoroethyl 2-chloro-2, 2-dichloroethyl, 2-dichloro-2-fluoroethyl, 2-trifluoroethyl, pentafluoroethyl, 1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 1-difluoropropyl 2, 2-difluoropropyl, 1, 2-difluoropropyl, 3-trifluoropropyl, heptafluoropropyl, 1-trifluoropropan-2-yl, 3-chloropropyl, or 4-chlorobutyl, and the like.
In the present invention, C 3 -C 10 Cycloalkyl denotes saturated cyclic hydrocarbon radicals having 3 to 10 carbon atoms, for example, monocyclic saturated hydrocarbon radicals (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl), or bicyclic saturated hydrocarbon radicals (e.g. bicyclo [ 3.1.0)]Hexyl, bicyclo [3.2.0]Heptyl, bicyclo [3.3.0]Octyl and bicyclo [4.2.0]Octyl and bicyclo [4.3.0]Nonyl, bicyclo[4.4.0]Decyl and bicyclo [2.2.1]Heptyl and bicyclo [3.1.1]Heptyl, bicyclo [2.2.2]Octyl and bicyclo [3.2.1]Octyl), and the like.
In the present invention, C 5 -C 9 Heterocyclyl represents heteroaryl having 5 to 9 carbon atoms containing 1,2,3 or 4 heteroatoms selected from N and O, for example, monocyclic heteroaryl (e.g. furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl, pyridyl, oxopyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, etc.), or bicyclic heteroaryl (e.g.
Etc., where x represents the point of attachment to the remainder of the molecule, and the point of attachment is not limited to being on the ring shown, but may be on either of the two rings).
In some embodiments of the invention, C 6 -C 10 Aryl groups can be, for example, phenyl or naphthyl, wherein C 6 -C 10 One or more-ch=in the aryl group may optionally be replaced by-n=independently, e.g. C 6 -C 10 One or more-ch=in the aryl group are each independently replaced by-n=to form, for example, a pyridyl group or a pyrimidinyl group, etc., or C 6 -C 10 -ch=in aryl is not substituted; wherein C is 6 -C 10 One or more-H in the aryl group may optionally be independently substituted with halogen, -CN, C, respectively 1 -C 5 Alkyl, or C 1 -C 5 Alkoxy substitution, e.g. C 6 -C 10 One or more-H in the aryl are each independently halogen, -CN, C 1 -C 5 Alkyl, or C 1 -C 5 Alkoxy groupSubstituted, or C 6 -C 10 the-H groups in the aryl groups are unsubstituted.
In some embodiments of the invention, the base is an inorganic base, preferably an alkali metal carbonate, alkali metal bicarbonate, alkali metal phosphate, alkali metal hydrogen phosphate or alkali metal hydroxide, further preferably sodium bicarbonate, sodium carbonate or potassium carbonate.
In the present invention, the amount of the base is 0.1 to 5 moles per mole of the compound of formula I or the compound of formula II which is not used in excess; preferably, the amount of base is 0.1 to 3 moles.
In some embodiments of the invention, the palladium catalyst is a palladium (II) salt or palladium (0) complex, preferably dichloro di-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II), bis (triphenylphosphine) palladium dichloride, tetrakis (triphenylphosphine) palladium, or palladium chloride. The catalyst has better dispersibility and thermal stability in the organic solvent, thereby improving the catalytic efficiency of the reaction; in addition, the selectivity of the catalyst for obtaining the product is very high, and the purity of the product is further improved.
In some embodiments of the invention, the reaction is carried out at a temperature of 50 ℃ to 140 ℃, preferably at a temperature of 60 ℃ to 80 ℃. If the reaction temperature is too low, the activation energy of the reaction is difficult to reach, and the reaction duration and the reaction yield are affected; if the reaction temperature is too high, the reaction yield and the product purity are not further improved, the equipment requirement on industrial production is greatly improved, and the safety is obviously reduced.
In some embodiments of the invention, the reaction time is 1 to 12 hours, preferably 4 to 8 hours. If the reaction time is too short, the reaction is incomplete, and the reaction yield is low; if the reaction time is too long, the reaction yield is not obviously improved, but the byproducts are gradually increased to influence the purity of the product.
In some embodiments of the invention, the reaction may be carried out by standard procedures for the Suzuki reaction, for example, by mixing all reagents (including catalyst or catalyst precursor and ligand, base and solvent mixtures) and reacting them at the desired temperature; alternatively, the reagents may be added stepwise, especially in the case of a continuous or semi-continuous process. The reaction is carried out under a blanket of inert gas (e.g., under an argon or nitrogen atmosphere) to avoid the presence of oxygen.
In some embodiments of the invention, the molar ratio of the compound of formula I to the compound of formula II is from 1:1 to 1:1.2.
In some embodiments of the invention, the amount of palladium catalyst calculated based on the Pd content is 0.00001 to 0.05 mole, if the compound of formula I and the compound of formula II are used in equimolar amounts, the amount of palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II, or if the compound of formula I and the compound of formula II are not used in equimolar amounts, the amount of palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II that is not used in excess.
In some embodiments of the invention, the amount of palladium catalyst calculated based on the Pd content is 0.00001 to 0.001 mole, if the compound of formula I and the compound of formula II are used in equimolar amounts, the amount of palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II, or if the compound of formula I and the compound of formula II are not used in equimolar amounts, the amount of palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II that is not used in excess.
In the present invention, water and an organic solvent constitute a solvent mixture, wherein water accounts for 0.1% -20% of the total weight of the solvent mixture; preferably, water comprises 0.5% to 18% of the total weight of the solvent mixture; further preferably, water comprises 1% to 15% of the total weight of the solvent mixture; particularly preferably, the water comprises 1% to 10% by weight of the total solvent mixture.
In the present invention, the amount of the organic solvent to be used is not particularly limited, but is premised on dissolution of the reactant.
The beneficial effects are that:
1. compared with the conventional anhydrous aprotic solvent, the organic solvent provided by the invention adopts the etherate of the dihydric alcohol, so that the generation of reaction byproducts can be effectively reduced, the reaction yield is higher, the product purity is higher, and the subsequent application of the product is not influenced;
2. the product of the invention is easier to separate from the reaction system, thereby reducing the economic cost and the time cost of post-treatment;
3. the solvent used in the invention has the characteristics of high flash point and no smell, so that the risk is lower, and the environment-friendly requirement is met;
therefore, the method for synthesizing the compound containing the biaryl structure through the Suzuki coupling reaction is favorable for realizing industrial production and has extremely high industrial application value.
Detailed Description
The invention will be described below in connection with specific embodiments. The following examples are illustrative of the present invention and are not intended to limit the present invention. Other combinations and various modifications within the inventive concept may be made without departing from the spirit or scope of the invention.
The reagents used in the following examples and comparative examples are commercially available.
The instruments and test methods used for the relevant data tests in examples and comparative examples are as follows:
the GC test instrument was an Agilent 7820A gas chromatograph, the carrier gas was helium (2 mL/min), the sample vaporization chamber was set at 280℃and the flame ion detector was set at 300 ℃. In separating the component compounds, capillary column DB1 (length: 30m, inner diameter: 0.32mm, film thickness: 0.25 μm, stationary liquid phase: dimethylpolysiloxane, no polarity) was kept at 180℃for 2 minutes, and then heated to 280℃at a rate of 5℃per minute. After preparing the sample to be measured into an acetone solution (0.1 wt%), 1. Mu.L was injected into the sample vaporization chamber.
The MS test instrument is an Agilent 7890B-5977A mass spectrometer, and the test conditions are as follows: EI source, ionization voltage of 70eV, ion source temperature of 250 ℃, scan range of 30-600 m/z.
Example 1
51.5g of 1-bromo-4- (4-propylcyclohexyl) benzene, 44.3g of (4-butoxy-2, 3-difluorophenyl) boric acid, 14.3g of sodium carbonate, 300mL of dipropylene glycol dimethyl ether and 120mL of water were placed in a 500mL reaction flask, and under a nitrogen atmosphere, the temperature was controlled at 70℃to 80℃and 0.012g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) was added to react for 5 hours. The solution was analyzed, the organic phase was directly frozen for crystallization, and after suction filtration, it was recrystallized once with dipropylene glycol dimethyl ether, and 64.93g of Compound A-1 (purity: 99.96% (GC), yield: 91.8%) as a white solid was obtained by suction filtration.
MS data for compound a-1: 219.1 (12%), 232.1 (24%), 245.1 (19%), 330.2 (31%), 386.3 (14%).
The following examples 2-3 and comparative examples 1-2 were identical in reaction formula to example 1, with only specific reaction conditions being changed.
Example 2
51.5g of 1-bromo-4- (4-propylcyclohexyl) benzene, 44.3g of (4-butoxy-2, 3-difluorophenyl) boric acid, 14.3g of sodium carbonate, 300mL of dipropylene glycol diethyl ether and 120mL of water were placed in a 500mL reaction flask, and under a nitrogen atmosphere, the temperature was controlled to 70℃to 80℃and 0.012g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) was added to react for 5 hours. The solution was analyzed, the organic phase was directly frozen for crystallization, and after suction filtration, it was recrystallized once with dipropylene glycol diethyl ether, and 64.08g of Compound A-1 (purity: 99.97% (GC), yield: 90.6%) was obtained as a white solid by suction filtration.
Example 3
51.5g of 1-bromo-4- (4-propylcyclohexyl) benzene, 44.3g of (4-butoxy-2, 3-difluorophenyl) boric acid, 14.3g of sodium carbonate, 300mL of dipropylene glycol diisopropyl ether and 120mL of water were placed in a 500mL reaction flask, and under nitrogen protection, the temperature was controlled to 70℃to 80℃and 0.012g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) was added to react for 5 hours. The solution was analyzed, and the organic phase was directly frozen for crystallization, and after suction filtration, recrystallized once with dipropylene glycol diisopropyl ether, 63.3g of Compound A-1 (purity: 99.96% (GC), yield: 89.5%) was obtained as a white solid by suction filtration.
Comparative example 1
51.5g of 1-bromo-4- (4-propylcyclohexyl) benzene, 44.3g of (4-butoxy-2, 3-difluorophenyl) boric acid, 14.3g of sodium carbonate, 240mL of toluene, 120mL of water and 120mL of ethanol are placed in a 500mL reaction flask, and under nitrogen protection, the temperature is controlled to 70-80 ℃, and 0.012g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) is added to react for 5 hours. Separating, extracting the water phase with 50mL toluene for 2 times, mixing the filtrates, drying, passing the filtrate through a silica gel column, spin-drying, adding 300mL petroleum ether, pulping, suction-filtering, recrystallizing with ethanol once, and suction-filtering to obtain 51.3g of the compound A-1 as a white solid (purity: 98.84% (GC), yield: 72.6%).
Comparative example 2
51.5g of 1-bromo-4- (4-propylcyclohexyl) benzene, 44.3g of (4-butoxy-2, 3-difluorophenyl) boric acid, 14.3g of sodium carbonate, 360mL of tetrahydrofuran and 120mL of water were placed in a 500mL reaction flask, and under nitrogen protection, the temperature was controlled at 70℃to 80℃and 0.012g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) was added to react for 5 hours. Separating, extracting the water phase with 50mL toluene for 2 times, mixing the filtrates, drying, passing the filtrate through a silica gel column, spin drying, adding 300mL petroleum ether, pulping, suction filtering, recrystallizing with ethanol once, and suction filtering to obtain 52.97g of compound A-1 (purity: 99.26% (GC), yield: 74.9%) as white solid.
Example 4
50g of 4-bromo-3-methylphenol, 38.72g of 4-hydroxyphenylboric acid, 47.16g of sodium bicarbonate, 300mL of dipropylene glycol dimethyl ether and 120mL of water are added into a 500mL reaction flask, the temperature is controlled to be 70-80 ℃ under the protection of nitrogen, and 0.085g of palladium chloride is added for reaction for 5 hours. The solution was analyzed, the organic phase was directly frozen for crystallization, after suction filtration, it was recrystallized once with dipropylene glycol dimethyl ether, and 44.10g of Compound A-2 (purity: 99.81% (GC), yield: 82.5%) as a white solid was obtained by suction filtration.
MS data for compound a-2: 77.0 (5%), 115.1 (6%), 131.0 (4%), 157.1 (3%), 181.1 (5%), 200.1 (77%).
Example 5
To a 500mL reaction flask, 38g of 2-fluoro-6-bromophenol, 46g of (4-butoxy-2, 3-difluorophenyl) boric acid, 50g of sodium bicarbonate, 300mL of dipropylene glycol dimethyl ether and 120mL of water were placed, and under nitrogen protection, the temperature was controlled to 70℃to 80℃and 0.025g of bis (triphenylphosphine) palladium dichloride was added to react for 5 hours. The solution was analyzed, the organic phase was directly frozen for crystallization, after suction filtration, it was recrystallized once with dipropylene glycol dimethyl ether, and 57.75g of compound A-3 (purity: 99.73% (GC), yield: 87.8%) as a white solid was obtained by suction filtration.
MS data for compound a-3: 143.1 (15%), 164.1 (20%), 191.1 (8%), 211.1 (11%), 240.1 (21%), 296.1 (25%).
Example 6
In a 500mL reaction flask, 14g of (4- (4-propylcyclohexyl) phenyl) boric acid, 20g of 5- ((4-bromophenyl) difluoromethoxy) -1,2, 3-trifluorobenzene, 14.3g of sodium bicarbonate, 150mL of dipropylene glycol dimethyl ether and 50mL of water were added, and under the protection of nitrogen, the temperature was controlled at 60℃to 70℃and 0.01g of dichlorodi-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) was added to react for 8 hours. Separating, directly freezing and crystallizing an organic phase, filtering, recrystallizing with dipropylene glycol dimethyl ether once, and filtering to obtain 24.0g of compound A-4 (purity: 99.98% (GC) and yield: 89.1%) as white solid.
MS data for compound a-4: 327 (75%), 363.1 (5%), 455.2 (6%), 474.2 (6%), 476.2 (8%).
As can be seen from the comparison of the above examples 1-3 and comparative examples 1-2, the present invention uses the etherate of glycol as the reaction solvent, which can effectively reduce the production of reaction byproducts, improve the reaction yield, have higher product purity, and have no influence on the subsequent application of the product. In addition, as can be seen from the above examples, the product of the present invention is easily separated from the reaction system, and the post-treatment method of the reaction is simpler, thereby reducing the economic cost and the time cost of the post-treatment; the solvent used in the invention has the characteristics of high flash point and no smell, so that the risk is lower, and the environment-friendly requirement is better met. Therefore, the method for synthesizing the compound containing the biaryl structure through the Suzuki coupling reaction is favorable for realizing industrial production and has extremely high industrial application value.
The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the present invention and to implement it, but not limit the scope of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of the present invention.

Claims (15)

1. A method for synthesizing a biaryl structure-containing compound by a Suzuki coupling reaction, wherein the biaryl structure-containing compound is a compound of formula a:
wherein,
R 1 and R is 2 Each independently represents hydrogen, cyano, thiocyano, isothiocyano, nitro, amino, C 1 -C 4 Alkylamino, halogen, C 1 -C 12 Non-halogenated alkyl, or C 1 -C 12 Haloalkyl groups, and one or more of the alkyl groups-CH 2 -may each be independently replaced by-O-, -S-, -CO-, -CS-, -ch=ch-, or-c≡c-, wherein-O-and/or-S-are not directly connected;
ring(s)And (C) a ring->Each independently represents C 6 Cycloalkyl or C 6 Aryl, said C 6 Cycloalkyl or C 6 One or more-H in the aryl group is optionally independently selected from halogen, C by 1,2 or 3 1 -C 6 Non-haloalkyl and C 1 -C 6 The substituents of the haloalkyl groups are substituted and one or more of the alkyl groups are-CH 2 -may each be independently replaced by-O-, -S-, -CO-, -CS-, -ch=ch-, or-c≡c-, wherein-O-and/or-S-are not directly connected;
ring(s)And (C) a ring->Each independently represents C 6 Aryl, said C 6 One or more-H in the aryl group is optionally independently selected from halogen, C by 1,2 or 3 1 -C 6 Non-haloalkyl and C 1 -C 6 Substituents of haloalkyl groups, one or more of the alkyl groups being-CH 2 -can be replaced independently of one another by-O-, -S-, -CO-, -CS-, -ch=ch-or-c≡c-, wherein-O-and/or-S-are not directly linked, and said C 6 One or more of the aryl groups-ch=can each independently be replaced by-n=and;
Z 1 and Z 2 Each independently represents a single bond, -O-, -ch=ch-, -CH 2 O-、-OCH 2 -、-CF 2 O-or-OCF 2 -；
a and b each independently represent 0 or 1;
characterized in that the method comprises the following steps:
the compound of formula I
With a compound of formula II in the presence of a base, a palladium catalyst, water and an organic solvent
Wherein,
x represents chlorine, bromine or iodine;
L 1 and L 2 Each independently represents a hydroxyl group, or, L 1 And L 2 Together form a bridging group-O- (C (R) a ) 2 ) q O-, wherein q is 2 or 3, R a Represents hydrogen or C 1 -C 3 An alkyl group;
R 1 ring and ringRing->Ring->Ring->Z 1 、Z 2 A and b are as defined above; and is also provided with
The organic solvent is one or more of dipropylene glycol dimethyl ether, dipropylene glycol diethyl ether and dipropylene glycol diisopropyl ether.
2. The method of claim 1, wherein the base is an inorganic base.
3. The method of claim 1, wherein the palladium catalyst is a palladium (II) salt or a palladium (0) complex.
4. The method of claim 1, wherein the reaction is carried out at a temperature of 50 ℃ to 140 ℃.
5. The method according to claim 1, wherein the reaction time of the reaction is 1 to 12 hours.
6. The method according to claim 1, wherein the reaction is carried out under the protection of an inert gas.
7. The method according to claim 1, wherein the molar ratio of the compound of formula I and the compound of formula II is 1:1 to 1:1.2.
8. The method according to claim 1, characterized in that the amount of the palladium catalyst calculated on the basis of the Pd content is 0.00001-0.05 mole, the amount of the palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II if the compound of formula I and the compound of formula II are used in equimolar amounts, or the amount of the palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II which is not used in excess if the compound of formula I and the compound of formula II are not used in equimolar amounts.
9. The method according to claim 8, wherein the amount of the palladium catalyst calculated based on the Pd content is 0.00001 to 0.001 mole, and if the compound of formula I and the compound of formula II are used in equimolar amounts, the amount of the palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II, or if the compound of formula I and the compound of formula II are not used in equimolar amounts, the amount of the palladium catalyst is determined with respect to 1 mole of the compound of formula I or the compound of formula II which is not used in excess.
10. The method of claim 1, wherein the organic solvent is dipropylene glycol dimethyl ether.
11. The method according to claim 2, wherein the base is an alkali metal carbonate, alkali metal bicarbonate, alkali metal phosphate, alkali metal hydrogen phosphate or alkali metal hydroxide.
12. The method according to claim 2, wherein the base is sodium bicarbonate, sodium carbonate or potassium carbonate.
13. A process according to claim 3, wherein the palladium catalyst is di-tert-butyl- (4-dimethylaminophenyl) phosphine palladium (II) dichloride, di (triphenylphosphine) palladium dichloride, tetra (triphenylphosphine) palladium, or palladium chloride.
14. The process of claim 4, wherein the reaction is carried out at a temperature of 60 ℃ to 80 ℃.
15. The method according to claim 5, wherein the reaction time of the reaction is 4 to 8 hours.
CN202011553254.8A 2020-12-24 2020-12-24 Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction Active CN114671745B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011553254.8A CN114671745B (en) 2020-12-24 2020-12-24 Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011553254.8A CN114671745B (en) 2020-12-24 2020-12-24 Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction

Publications (2)

Publication Number Publication Date
CN114671745A CN114671745A (en) 2022-06-28
CN114671745B true CN114671745B (en) 2024-04-05

Family

ID=82069783

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011553254.8A Active CN114671745B (en) 2020-12-24 2020-12-24 Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction

Country Status (1)

Country Link
CN (1) CN114671745B (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101328108A (en) * 2008-08-04 2008-12-24 上海万溯化学有限公司 Preparation of 1-(3',5'- difluoro) phenyl-4-(4''- -alkylphenyl)-2-fluorobenzene
CN102399117A (en) * 2010-09-16 2012-04-04 石家庄诚志永华显示材料有限公司 Method for synthesis of 2'-fluoro terphenyl liquid crystal
CN102659509A (en) * 2012-04-01 2012-09-12 烟台海川化学制品有限公司 Preparation method of biphenyl liquid crystal compound
CN103980098A (en) * 2014-05-16 2014-08-13 上海康鹏化学有限公司 Preparation method of CF2O-contained monomer liquid crystal compound
CN109082280A (en) * 2018-11-05 2018-12-25 宁夏中星显示材料有限公司 A kind of preparation method of liquid crystal material

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101328108A (en) * 2008-08-04 2008-12-24 上海万溯化学有限公司 Preparation of 1-(3',5'- difluoro) phenyl-4-(4''- -alkylphenyl)-2-fluorobenzene
CN102399117A (en) * 2010-09-16 2012-04-04 石家庄诚志永华显示材料有限公司 Method for synthesis of 2'-fluoro terphenyl liquid crystal
CN102659509A (en) * 2012-04-01 2012-09-12 烟台海川化学制品有限公司 Preparation method of biphenyl liquid crystal compound
CN103980098A (en) * 2014-05-16 2014-08-13 上海康鹏化学有限公司 Preparation method of CF2O-contained monomer liquid crystal compound
CN109082280A (en) * 2018-11-05 2018-12-25 宁夏中星显示材料有限公司 A kind of preparation method of liquid crystal material

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
陈润峰.有机化学与光电材料实验教程.南京：东南大学出版社,2019,(第2019年10月第1版),174. *

Also Published As

Publication number Publication date
CN114671745A (en) 2022-06-28

Similar Documents

Publication Publication Date Title
KR102100539B1 (en) Mono- and Dialkyl Ethers of Furan-2,5-Dimethanol and (Tetra-hydrofuran-2,5-diyl)dimethanol and Amphiphilic Derivatives Thereof
CN107235923B (en) Preparation method of 3-aryl quinoxalinone derivatives
BRPI0813960B1 (en) biaryl production process
CN103265420A (en) Preparation method of aromatic diketone compound
CN112521282A (en) Bepaidic acid intermediate and synthesis method thereof
JP7445606B2 (en) Method for preparing haloalkanesulfonic acids from sulfur trioxide and haloalkanes
CN114671745B (en) Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction
CN110325513B (en) Process for preparing substituted biphenyls
CN114671744B (en) Green method for synthesizing biaryl structure-containing compound through Suzuki coupling reaction
CN106946648B (en) Fluorene compound and method for producing fluorene compound
KR101912643B1 (en) Fluorosulfonyl-substituted bis(aryl)acetal compounds
CN113402476B (en) Imine oxazine derivative and preparation method thereof
US20120016152A1 (en) Process for the preparation of 4`-haloalkylbiphenyl-2-carboxylic acids
CN103601745B (en) Preparation method of commonly used acetamidopyridine boronic acid pinacol ester
EP3722289A1 (en) Method for producing 2-substituted-3-ethylsulfonyl pyridine compound and like
AU2017239848A1 (en) Novel compound and synthesis method therefor
CA2764241C (en) Disubstituted-aminodifluorosulfinium salts, process for preparing same and method of use as deoxofluorination reagents
JP2022516863A (en) Preparation of sulfonamide herbicide process intermediate products
JP2017071556A (en) Manufacturing method of carboxylic acid prenyl and prenol using oxovanadium complex
CN114805017B (en) Preparation method of 2-fluoro-1, 5-hexadiene compound
CN114426531B (en) Compound containing trans-1, 3-dioxane ring and preparation method and application thereof
CN114804998B (en) Preparation method of 3-substituted 2-fluoro-1, 5-diene compound
CN104245672B (en) Prepare the method for roflumilast
CN112159336B (en) Preparation method of high-purity aryne substituted nitrile compound
CN110015987B (en) Preparation method of 2,3 '-dimethoxy- [2,4' ] bipyridyl

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