Method for preparing green and environment-friendly biaryl structure compound through Suzuki coupling reaction

Abstract

The invention specifically discloses a method for preparing a green and environment-friendly biaryl structure compound through Suzuki coupling reaction, which comprises the following steps: mixing an aryl halide I with a compound II of aryl phenylboronic acid in the presence of a metal alkali salt, a catalyst and a reaction solvent system, heating, and reacting to obtain the biaryl structure compound, a reaction solvent system is a single organic solvent and water, and the organic solvent is straight-chain alkane or aromatic ring hydrocarbon and is immiscible with water; the molar ratio of the aryl halide I to the compound II is (1: 1)-(1: 1.5), the heating temperature is 70-90 DEG C, and the reaction time is 4-10 hours. According to the method provided by the invention, the biaryl structure compound is prepared, and the selected reaction solvent system is straight-chain alkane or aromatic ring hydrocarbon, so that the generation of reaction byproducts can be effectively reduced, the reaction yield is higher, the product purity is higher, the subsequent application of the product is not influenced, and the method is economical, environment-friendly and higher in purity, and has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction. Background Art

[0002] Suzuki coupling (also known as Suzuki-Miyaura coupling, Suzuki reaction, or Suzuki-Miyaura reaction) is a relatively new cross-coupling reaction, in which aromatic or alkenyl boronic acid or boric ester cross-couples with chlorine, bromine, iodine aromatic hydrocarbons or alkenes under the catalysis of zero-valent palladium complexes. The reaction was first reported by Suzuki Akira in 1979 and is widely used in organic synthesis. It has strong substrate adaptability and functional group tolerance and is often used to synthesize polyolefins, styrene and biphenyl derivatives, and is thus used in the synthesis of many natural products and organic materials.

[0003] In the preparation process of liquid crystal materials, it is very common to use Suzuki coupling reaction to prepare compounds containing biaryl structures. For example, Chinese patent application CN102307838A discloses the use of Suzuki coupling reaction to construct biphenyl structure. However, the reaction yield can only reach about 70%, and because the product is difficult to separate from the reaction solvent, it needs to be post-processed by extraction and other processes, which does not meet the high standards of modern chemistry for green environmental protection.

[0004] Therefore, there is an urgent need to optimize and improve the method of synthesizing compounds containing biaryl structures by Suzuki coupling reaction, in order to develop a method with higher reaction yield, more convenient post-processing, higher production capacity, and more economical and environmentally friendly. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction. The preparation of the biaryl structure compound by the method provided by the present invention is economical, environmentally friendly and has higher purity.

[0006] The technical solution of the present invention is achieved in this way:

[0007] A method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction comprises the following steps:

[0008] The aryl halide I is mixed with the aryl phenylboronic acid compound II in the presence of a metal alkali salt, a catalyst and a reaction solvent system, and then heated to react to obtain the biaryl structure compound;

[0009] The reaction solvent system is a single organic solvent and water, and the organic solvent is a straight-chain alkane or an aromatic hydrocarbon, which is immiscible with water;

[0010] The molar ratio of the aryl halide I to the compound II is 1:1-1:1.5, the heating temperature is 70-90°C, and the reaction time is 4-10h.

[0011] Furthermore, the aryl halide I is one of propylcyclobromobenzene, dichlorobenzene, trichlorobenzene, dibromobenzene, isotribromobenzene, isotetrabromobenzene and the like.

[0012] Furthermore, the compound II is one of 2,3-difluoro-4-ethoxyphenylboronic acid, 4-acetylphenylboronic acid, 4-aminophenylboronic acid, and the like.

[0013] Furthermore, the metal alkali salt is one or more of sodium carbonate, potassium carbonate and sodium bicarbonate.

[0014] Furthermore, the amount of the metal alkali salt used is calculated based on the alkali content and is 0.5-0.9 of the smaller amount of the amount of the aryl halide I and the aryl phenylboronic acid compound II.

[0015] Furthermore, the catalyst is a palladium (II) salt or a palladium (0) complex, preferably one or more of di-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II) dichloride, bis(triphenylphosphine)palladium dichloride, tetrakis(triphenylphosphine)palladium, and palladium chloride.

[0016] Furthermore, the amount of the catalyst used is calculated based on the palladium content and is 0.0001-0.001 of the smaller amount of the amount of the aryl halide I and the arylphenylboronic acid compound II.

[0017] These catalysts can have good dispersibility and thermal stability in the organic solvent of the present invention, thereby improving the catalytic efficiency of the reaction; in addition, the selectivity of the products obtained by catalysis of these catalysts is very high, further improving the purity of the products.

[0018] Furthermore, the reaction solvent system is a two-component system, one part is water, the amount of which is 20-40% of the total volume of the solvent; the other part is organic matter, preferably one or more of straight-chain alkanes and aromatic hydrocarbons.

[0019] Furthermore, the amount of the solvent is calculated based on the organic matter, and the concentration is 1-3 mol / L; the volume reference value is the volume amount of the smaller amount of the substance in the aryl halide I and the aryl phenylboronic acid compound II.

[0020] If the reaction temperature is too low, it is difficult to reach the activation energy of the reaction, which will affect the reaction time and reaction yield; if the reaction temperature is too high, it will not further improve the reaction yield and product purity, but will greatly increase the requirements for industrial production equipment and significantly reduce safety. If the reaction time is too short, the reaction is incomplete and the reaction yield is low; if the reaction time is too long, it will not significantly improve the reaction yield, but will gradually increase the by-products and affect the product purity.

[0021] Furthermore, the reaction needs to be carried out under the protection of an inert gas, preferably an argon or nitrogen atmosphere.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. Selecting a reaction solvent system of straight-chain alkanes or aromatic hydrocarbons can effectively reduce the generation of reaction by-products, increase the reaction yield, increase the product purity, and have no effect on the subsequent application of the product.

[0024] 2. The selected solvent is incompatible with water, and the reaction solvent system is a single organic solvent and water. The reaction product is soluble in a single organic solvent and insoluble in water. The target product and the organic solvent can be separated by simply standing and separating the liquids, which reduces the economic and time costs of post-processing. The VOC content in the wastewater is lower, which is easier to handle, more economical and environmentally friendly.

[0025] 3. High concentration reaction system, higher product capacity, more economical and energy-saving.

[0026] 4. The reaction conditions are milder, the requirements for production equipment are lower, and it is more suitable for large-scale industrial production. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Reagent Description

[0029] 90-120℃ petroleum ether-industrial grade (GC≥99.5%), toluene-industrial grade (GC≥99.5%).

[0030] Example 1

[0031] 20.6 g of 2,3-difluoro-4-ethoxyphenylboronic acid, 281 g of propylcyclobromobenzene, 7.42 g of sodium carbonate, 0.01416 g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 67 mL of petroleum ether and 22 mL of water were coupled at an internal temperature of 75°C and nitrogen protection conditions for 6 hours after GC overcontrol. After the reaction, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether. The organic phases were combined and dried with anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, flushed with petroleum ether, and distilled under reduced pressure at 70°C. The obtained solid was purified by recrystallization with 4-fold ethanol. The reaction overcontrol purity was 97.5%, and the yield was 94.4% when the purification purity was ≥99.9%;

[0032] Example 2

[0033] 25.8 g of 2,3-difluoro-4-ethoxyphenylboronic acid, 281 g of propylcyclobromobenzene, 7.42 g of sodium carbonate, 0.01416 g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 200 mL of petroleum ether and 67 mL of water were subjected to coupling reaction at an internal temperature of 75°C and nitrogen protection for 6 hours, and the GC was over-controlled. After the reaction was completed, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether, the organic phases were combined, and dried with anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, and the column was flushed with petroleum ether, and the solid was distilled under reduced pressure at 70°C. The obtained solid was recrystallized and purified with 4-fold ethanol, and the reaction over-controlled purity was 82.3%. When the purification purity was ≥99.9%, the yield was 80.7%;

[0034] Example 3

[0035] 30.9 g of 2,3-difluoro-4-ethoxyphenylboronic acid, 281 g of propylcyclobromobenzene, 4.24 g of sodium carbonate, 0.01416 g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 67 mL of petroleum ether and 22 mL of water were coupled at an internal temperature of 75°C and nitrogen protection conditions for 6 hours, and after the reaction, the GC was over-controlled. After the reaction was completed, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether, the organic phases were combined, and dried with anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, and the column was flushed with petroleum ether, and the solid was distilled under reduced pressure at 70°C. The obtained solid was recrystallized and purified with 4-fold ethanol. The reaction over-controlled purity was 84.3%, and the yield was 82.1% when the purification purity was ≥99.9%;

[0036] Example 4

[0037] 192 g of 4-acetylphenylboronic acid, 281 g of propylcyclobromobenzene, 4.24 g of sodium carbonate, 0.00354 g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 67 mL of petroleum ether and 22 mL of water were coupled at an internal temperature of 75° C. and nitrogen protection conditions for 6 hours. After the reaction, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether. The organic phases were combined and dried over anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, flushed with petroleum ether, and distilled under reduced pressure at 70° C. The obtained solid was purified by recrystallization with 4-fold ethanol. The reaction purity was 89.4%, and the yield was 81.4% when the purification purity was ≥99.9%;

[0038] Example 5

[0039] 288g of 4-acetylphenylboronic acid, 181g of trichlorobenzene, 7.42g of sodium carbonate, 0.01416g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 67mL of petroleum ether and 22mL of water were coupled at an internal temperature of 75°C and nitrogen protection conditions for 6 hours after GC overcontrol. After the reaction, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether. The organic phases were combined and dried over anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, flushed with petroleum ether, and distilled under reduced pressure at 70°C. The obtained solid was purified by recrystallization with 4-fold ethanol. The reaction overcontrol purity was 94.5%, and the yield was 91.3% when the purification purity was ≥99.9%;

[0040] Example 6

[0041] 137 g of 4-acetylphenylboronic acid, 315 g of tribromobenzene, 7.42 g of sodium carbonate, 0.0708 g of catalyst dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II), 67 mL of petroleum ether and 22 mL of water were coupled at an internal temperature of 75° C. and nitrogen protection conditions for 6 hours. After the reaction, the mixture was washed with water twice, and the aqueous phase was extracted twice with petroleum ether. The organic phases were combined and dried over anhydrous sodium sulfate. After drying, the organic liquid was passed through a 0.3-fold silica gel chromatography column, and the column was flushed with petroleum ether. The solid was distilled under reduced pressure at 70° C. and purified by recrystallization with 4-fold ethanol. The reaction purity was 97.8%, and the yield was 94.9% when the purification purity was ≥99.9%.

[0042] The tests and results are shown in Table 1.

[0043] Table 1

[0044] project GC overcontrol Yield Example 1 97.5％ 94.4％ Example 2 82.3％ 80.7％ Example 3 84.3％ 82.1％ Example 4 89.4％ 81.4％ Example 5 94.5％ 91.3％ Example 6 97.8％ 94.9％

[0045] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction, characterized in that: The steps include: The aryl halide I is mixed with the aryl phenylboronic acid compound II in the presence of a metal alkali salt, a catalyst and a reaction solvent system, and then heated to react to obtain the biaryl structure compound; The reaction solvent system is a single organic solvent and water, and the organic solvent is a straight-chain alkane or an aromatic hydrocarbon, which is immiscible with water; The molar ratio of the aryl halide I to the compound II is 1:1-1:1.5, the heating temperature is 70-90°C, and the reaction time is 4-10h.

2. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The aryl halide I is one of propylcyclobromobenzene, dichlorobenzene, trichlorobenzene, dibromobenzene, s-tribromobenzene and s-tetrabromobenzene.

3. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The compound II is one of 2,3-difluoro-4-ethoxyphenylboronic acid, 4-acetylphenylboronic acid and 4-aminophenylboronic acid.

4. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The metal alkali salt is one or more of a sodium metal alkali salt and a potassium metal alkali salt.

5. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 4, characterized in that: The amount of the metal alkali salt used is calculated based on the alkali content and is 0.5-0.9 of the smaller amount of the aryl halide I and the aryl boronic acid compound II.

6. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The catalyst is a palladium (II) salt or a palladium (0) complex, preferably one or more of di-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II) dichloride, bis(triphenylphosphine)palladium dichloride, tetrakis(triphenylphosphine)palladium, and palladium chloride.

7. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 6, characterized in that: The amount of the catalyst used is calculated based on the palladium content and is 0.0001-0.001 of the smaller amount of the amount of the aryl halide I and the aryl boronic acid compound II.

8. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The reaction solvent system is a two-component system, one part is water, the dosage of which is 20-40% of the total volume of the solvent; the other part is organic matter, which is one or more of straight-chain alkanes and aromatic hydrocarbons.

9. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The amount of solvent used is calculated based on organic matter, and the concentration is 1-3 mol / L; the volume reference value is the volume amount of the smaller value of the amount of the substance in the aryl halide I and the aryl phenylboronic acid compound II.

10. The method for preparing a green and environmentally friendly biaryl structure compound by Suzuki coupling reaction according to claim 1, characterized in that: The reaction needs to be carried out under the protection of an inert gas, preferably an argon or nitrogen atmosphere.