Synthesis method and application of a 2-nitro-1,1'-biphenyl compound

Abstract

The present invention discloses a method for synthesizing 2-nitro-1,1'-biphenyl compounds and their applications. Using 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compounds as raw materials, a reaction is carried out in the presence of a catalyst, a solvent and an oxidant to obtain 2-nitro-1,1'-biphenyl compounds. The synthesis method of the present invention has a reaction yield of 90.2%-94.8%, and the dehydrogenation aromatization reaction involved has high selectivity, low cost, easy operation, less pollution and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of the preparation of organic compounds, and particularly relates to a preparation method and application of 2-nitro-1,1'-biphenyl compounds. Background Art

[0002] 2-Nitro-1,1'-biphenyl compounds are important pesticide intermediates. For example, 4'-chloro-2-nitro-1,1'-biphenyl is a key intermediate for the synthesis of boscalid. CAS registration number: 1204-44-0. Boscalid is a new type of nicotinamide fungicide developed by BASF of Germany. The common name is boscalid, also known as nicobifen, test number BAS510. It is a mitochondrial respiration inhibitor, a succinate dehydrogenase inhibitor (SDHI). It acts by inhibiting succinate coenzyme Q reductase (also known as complex II) on the mitochondrial electron transport chain. Its mechanism of action is similar to that of other amide and benzamide fungicides. It is mainly used to control powdery mildew, gray mold, various rot diseases, brown rot diseases and root rot diseases, etc. It has activity against almost all types of fungal diseases and is also effective against resistant bacteria to other agents. 3',4',5-Trifluoro-2-nitro-1,1'-biphenyl is an important intermediate for the synthesis of fluxapyroxad. Fluxapyroxad (obtained the ISO common name for pesticides: Fluxapyroxad in April 2015, trade name: Xemium) is a succinate dehydrogenase inhibitor fungicide developed by BASF. Fluxapyroxad is a mitochondrial respiration inhibitor, a succinate dehydrogenase inhibitor (SDHI). SDHI fungicides act by inhibiting the succinate dehydrogenase of pathogens, interfering with mitochondrial respiration, causing the pathogens to be unable to synthesize energy normally, and then exhausting and dying to achieve the purpose of controlling diseases. In 2012, BASF launched fluxapyroxad, which is used for grains, soybeans, corn, rapeseed, etc. in the Americas and Europe. BASF SE has applied for administrative protection in China, and the validity period of this administrative protection is until 2026.

[0003] There are many reports on the synthesis methods of 2-nitro-1,1′-biphenyl compounds. The synthetic routes can be roughly divided into: Suzuki coupling reaction route, Grignard reaction route, Diels-Alder cycloaddition reaction route and other synthetic routes. There are many relevant research reports on the synthesis of 2-nitro-1,1′-biphenyl compounds by the Suzuki coupling reaction route, mainly focusing on the selection of raw materials and the optimization of ligands. For example, 2-chloronitrobenzene and disubstituted phenylboronic acid are catalyzed by Pd / C in the presence of a non-phosphine ligand to carry out the Suzuki coupling reaction, with a yield of 91% - 95%. There is also a method using o-chloronitrobenzene and potassium 4-chlorotrifluorophenylborate as raw materials, adding a phase transfer catalyst and a cyclopalladium-based catalyst, and reacting under heating conditions in an aqueous solution to obtain 4′-chloro-2-nitro-1,1′-biphenyl, and the reaction is carried out under weak base conditions. There is also a method that uses bis(di-tert-butylphenylphosphine)palladium dichloride as the Suzuki coupling reaction catalyst, which improves the reaction efficiency and effectively controls the generation of impurities. The route for synthesizing 4′-chloro-2-nitro-1,1′-biphenyl using 4-chlorophenylboronic acid as the main raw material through the Suzuki reaction has the advantages of high yield and mature technology, but the disadvantages are also obvious: it requires the use of expensive palladium catalysts, and the raw material cost of 4-chlorophenylboronic acid is high. For example, for the raw material 4-chlorophenylboronic acid, its synthesis methods include the organolithium reagent method, the Grignard reagent method and the palladium-catalyzed oxyboration method. Industrially, the organolithium reagent method and the Grignard reagent method are mainly used. The organolithium reagent method produces high-quality 4-chlorophenylboronic acid products, followed by the Grignard reagent method. Both have difficulties such as harsh synthesis conditions, high safety risks and large amounts of "three wastes", resulting in high production costs of 4-chlorophenylboronic acid. A. Korte et al. reported a cycloaddition synthesis route: using 4-chlorobenzaldehyde (or 3,4,5-trifluorobenzaldehyde) as the raw material, through the Henry reaction, Diels-Alder cycloaddition reaction, halogenation, elimination oxidation and other reactions to obtain 4′-chloro-2-nitro-1,1'-biphenyl (or 3′,4′,5′-trifluoro-2-nitro-1,1'-biphenyl). This route has a low overall yield, uses a large variety of raw materials, has cumbersome operations, great difficulty in post-treatment and a large amount of "three wastes", making industrial production difficult. There is a method to improve on this basis: using 2-nitroaryl ethylene and substituted 1,3-butadiene as raw materials to react at 60 - 160 °C and 0.2 - 4.0 MPa to obtain 2-nitro-1,1'-biphenyl compounds, 2-nitro-1,1'-biphenyl compounds or their mixtures in one step, and then reducing them to prepare 2-nitro-1,1'-biphenyl compounds. This scheme reduces the reaction steps, but has a low yield, the raw materials are not easily available, and it is difficult to be applied industrially.

[0004] Therefore, it is of great significance to develop a preparation method of 2-nitro-1,1'-biphenyl compounds with high product yield, low raw material cost and little environmental pollution. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems existing in the prior art. For this purpose, the present invention provides a method for synthesizing 2-nitro-1,1'-biphenyl compounds and their applications. The preparation method has high reaction selectivity, high yield, low cost, easy operation, less pollution, and is suitable for large-scale industrial production.

[0006] The second aspect of the present invention provides the application of the 2-nitro-1,1'-biphenyl compounds obtained by the synthesis method in the preparation of pesticide compounds.

[0007] According to an embodiment of the first aspect of the present invention, a method for synthesizing 2-nitro-1,1'-biphenyl compounds uses 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compounds shown in Formula I as raw materials, and reacts in the presence of a catalyst, a solvent, and an oxidant to obtain 2-nitro-1,1'-biphenyl compounds shown in Formula II. The reaction formula is as follows:

[0008]

[0009] R 1 、R 2 、R 3 、R 4 and R 5 are each independently selected from hydrogen, fluorine, chlorine, bromine, or an alkoxy group, and the alkoxy group is selected from methoxy, ethoxy, propoxy, isopropoxy, or benzyloxy;

[0010] The catalyst includes a manganese catalyst and a phase transfer catalyst;

[0011] The oxidant includes an aqueous solution of hypochlorite.

[0012] According to the embodiment of the first aspect of the present invention, it has at least the following beneficial effects:

[0013] (1) The reaction has a high conversion rate, good selectivity, and the yield reaches 90.2%-94.8%.

[0014] (2) In the present invention, the raw material cost is low, the operation is easy, the pollution is less, and it is suitable for large-scale industrial production.

[0015] According to some embodiments of the present invention, the solvent includes at least one of dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, dioxane, and chlorobenzene.

[0016] According to some preferred embodiments of the present invention, the solvent includes dichloroethane.

[0017] According to some embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the solvent is 1:2 to 6.

[0018] According to some preferred embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the solvent is 1:3 to 4.

[0019] According to some embodiments of the present invention, the manganese catalyst includes manganese nitrate.

[0020] According to some preferred embodiments of the present invention, the manganese catalyst includes at least one of manganese acetate, manganese acetylacetonate, manganese sulfate, manganese nitrate, and manganese chloride.

[0021] According to some embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the manganese catalyst is 1:0.005 to 0.1.

[0022] According to some preferred embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the manganese catalyst is 1:0.009 to 0.1.

[0023] According to some embodiments of the present invention, the phase transfer catalyst includes at least one of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogensulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, and 4-dimethylaminopyridine.

[0024] According to some preferred embodiments of the present invention, the phase transfer catalyst includes tetrabutylammonium hydrogensulfate.

[0025] According to some embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the phase transfer catalyst is 1:0.001 to 0.01.

[0026] According to some preferred embodiments of the present invention, the mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the phase transfer catalyst is 1:0.004 to 0.005.

[0027] According to some embodiments of the present invention, the aqueous solution of the hypochlorite includes at least one of an aqueous solution of sodium hypochlorite, an aqueous solution of potassium hypochlorite, and an aqueous solution of calcium hypochlorite.

[0028] According to some preferred embodiments of the present invention, the aqueous solution of the hypochlorite includes an aqueous solution of sodium hypochlorite.

[0029] According to some embodiments of the present invention, the mass concentration of the aqueous solution of the hypochlorite is 10% to 30%.

[0030] According to some embodiments of the present invention, the molar ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the oxidant is 1:2 to 5.

[0031] According to some preferred embodiments of the present invention, the molar ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the oxidant is 1:2 to 3.

[0032] According to some embodiments of the present invention, the reaction time is 1 to 6 h, and the reaction temperature is 0 to 60 °C.

[0033] According to some preferred embodiments of the present invention, the reaction time is 1 to 2 h, and the reaction temperature is 50 to 60 °C.

[0034] According to some embodiments of the present invention, after the reaction, liquid separation is performed to obtain an organic phase.

[0035] According to some embodiments of the present invention, after the reaction, impurity removal is further included.

[0036] According to some embodiments of the present invention, the steps of impurity removal include washing the organic phase with water, then removing the solvent and performing recrystallization.

[0037] According to some embodiments of the present invention, the solvent for recrystallization includes methanol.

[0038] According to some embodiments of the present invention, the yield of the reaction is 90.2% - 94.8%.

[0039] Embodiments of the second aspect of the present invention provide the application of the 2-nitro-1,1'-biphenyl compound obtained by the said synthesis method in the preparation of pesticide compounds.

[0040] According to some embodiments of the present invention, the pesticide compounds include boscalid and fluxapyroxad. Detailed Embodiments

[0041] The following will clearly and completely describe the concept of the present invention and the technical effects produced in combination with the embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0042] Example 1:

[0043] This example provides a preparation method of the 2-nitro-1,1'-biphenyl compound of the present invention, which is the following steps:

[0044] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl (self-made, the preparation method refers to reference document CN 102348675B) and 96.03 g of dichloromethane into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese acetate and 0.24 g of tetrabutylammonium bromide. After heating to 30 °C, dropwise add an aqueous solution of 148.88 g of sodium hypochlorite (mass fraction 15%). After the addition is complete, continue the reaction at the same temperature for 4 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, and add methanol for recrystallization to obtain 21.96 g of light yellow solid 4'-chloro-2-nitro-1,1'-biphenyl, with a content of 97.85% and a yield of 92.2%. Melting point: 64.3 - 64.6 °C. LC-MS (m / z): 234.1 (M+H + ); 1 H-NMR (600 MHz, CDCl3): δ = 7.23 (s, 1H), 7.24 (s, 1H), 7.39 - 7.42 (m, 3H), 7.51 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 5.4 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), which proves that 4'-chloro-2-nitro-1,1'-biphenyl is successfully prepared.

[0045] Example 2:

[0046] This example provides a preparation method of the 2-nitro-1,1'-biphenyl compound of the present invention, which is the following steps:

[0047] Add 28.79 g (98%, 0.1 mol) of 4'-bromo-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl (self-made, the preparation method refers to reference document CN 102348675B) and 143.95 g of dichloromethane into a 500 mL three-necked flask. After stirring and dissolving, add 2.88 g of manganese acetylacetonate and 0.23 g of benzyltriethylammonium chloride. After heating to 40 °C, dropwise add an aqueous solution of 231.40 g of potassium hypochlorite (mass fraction 20%). After the addition is complete, continue the reaction at the same temperature for 4 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, and add methanol for recrystallization to obtain 26.60 g of brown solid 4'-bromo-2-nitro-1,1'-biphenyl, with a content of 97.76% and a yield of 93.5%. Melting point: 85.1 - 85.6 °C. LC-MS (m / z): 279.2 (M+H + ); 11H-NMR (600 MHz, CDCl3): δ = 6.97 (s, 1H), 7.14 (s, 1H), 7.33 - 7.37 (m, 3H), 7.49 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 5.4 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), which proved the successful preparation of 4'-bromo-2-nitro-1,1'-biphenyl.

[0048] Example 3:

[0049] This example provides a preparation method of the 2-nitro-1,1'-biphenyl compound of the present invention, which is the following steps:

[0050] Add 25.98 g (99%, 0.1 mol) of 3',4',5'-trifluoro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl (self-made, the preparation method refers to the reference document CN 102348675B) and 155.88 g of chloroform into a 500 mL three-necked flask. After stirring and dissolving, add 0.13 g of manganese sulfate and 0.16 g of tetrabutylammonium chloride. Heat to 50 °C and then dropwise add an aqueous solution (mass fraction 25%) of 114.38 g of calcium hypochlorite. After the addition is completed, continue to keep the temperature for reaction for 2 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, add methanol for recrystallization to obtain 24.57 g of light yellow solid 3',4',5'-trifluoro-2-nitro-1,1'-biphenyl, with a content of 97.67% and a yield of 94.8%. Melting point: 81.0 - 81.1 °C. LC-MS (m / z): 254.2 (M + H + ) 1 1H-NMR (300 MHz, CDCl3): δ = 6.91 - 6.96 (m, 2H), 7.39 (dd, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.57 (td, J = 8.1 Hz, J = 1.5 Hz, 1H), 7.66 (td, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.94 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H), which proved the successful preparation of 3',4',5'-trifluoro-2-nitro-1,1'-biphenyl.

[0051] Example 4:

[0052] This example provides a preparation method of the 2-nitro-1,1'-biphenyl compound of the present invention, which is the following steps:

[0053] Add 24.41 g (98%, 0.1 mol) of 3',4'-difluoro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl (self-made, the preparation method refers to reference document CN 102348675B) and 93.23 g of 1,2-dichloroethane into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese nitrate and 0.10 g of tetrabutylammonium hydrogensulfate. Heat to 60 °C and then dropwise add an aqueous solution of 74.44 g of sodium hypochlorite (mass fraction 30%). After the addition is complete, continue to hold the reaction for 1 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, add methanol for recrystallization to obtain 22.34 g of yellow solid 3',4'-difluoro-2-nitro-1,1'-biphenyl, with a content of 97.58% and a yield of 92.7%. The melting point is 77.2 - 77.8 °C. LC-MS (m / z): 236.2 (M+H + ); 1 H-NMR (300 MHz, CDCl3): δ = 6.90 - 6.98 (m, 3H), 7.41 (dd, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.55 (td, J = 8.1 Hz, J = 1.5 Hz, 1H), 7.64 (td, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.89 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H), which proves that 3',4'-difluoro-2-nitro-1,1'-biphenyl is successfully prepared.

[0054] Example 5:

[0055] This example provides a preparation method of the 2-nitro-1,1'-biphenyl compound of the present invention, which is the following steps:

[0056] Add 23.80 g (98%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 47.61 g of tetrahydrofuran into a 500 mL three-necked flask. After stirring and dissolving, add 1.19 g of manganese chloride and 0.05 g of trioctylmethylammonium chloride. Heat to 40 °C and then dropwise add an aqueous solution (mass fraction 25%) of 228.77 g of calcium hypochlorite. After the addition is complete, continue the reaction while maintaining the temperature for 3 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, and add methanol for recrystallization to obtain 21.20 g of light yellow solid 4'-methoxy-2-nitro-1,1'-biphenyl, with a content of 97.95% and a yield of 90.6%. The melting point is 58.1 - 58.7 °C. LC-MS (m / z): 230.3 (M + H+); 1H-NMR (600 MHz, CDCl3): δ = 3.90 (s, 3H), 6.92 (s, 1H), 7.17 (s, 1H), 7.33 - 7.37 (m, 3H), 7.53 (d, J = 7.8 Hz, 1H), 7.63 (d, J = 5.4 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), which proves that 4'-methoxy-2-nitro-1,1'-biphenyl is successfully prepared.

[0057] Example 6:

[0058] This example provides a method for preparing a 2-nitro-1,1'-biphenyl compound of the present invention, which comprises the following steps:

[0059] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 120.04 g of dioxane into a 500 mL three-necked flask. After stirring and dissolving, add 1.20 g of manganese acetate and 0.02 g of dodecyltrimethylammonium chloride. Control the temperature at 20 °C and dropwise add an aqueous solution (mass fraction 20%) of 231.40 g of potassium hypochlorite. After the addition is complete, continue the reaction while maintaining the temperature for 4 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, and add methanol for recrystallization to obtain 21.69 g of light yellow solid 4'-chloro-2-nitro-1,1'-biphenyl, with a content of 98.32% and a yield of 91.5%.

[0060] Example 7:

[0061] This example provides a method for preparing a 2-nitro-1,1'-biphenyl compound of the present invention, which comprises the following steps:

[0062] In a 500 mL three-necked flask, 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 144.05 g of chlorobenzene were added. After stirring and dissolving, 2.40 g of manganese acetylacetonate and 0.12 g of tetradecyltrimethylammonium chloride were added. While controlling the temperature at 0 °C, an aqueous solution of 198.51 g of sodium hypochlorite (mass fraction 15%) was added dropwise. After the addition was completed, the reaction was continued under warming for 6 h. After the reaction ended, liquid separation was carried out. The organic phase was washed with water, the solvent was removed, and recrystallization was carried out with methanol to obtain 21.30 g of a light yellow solid, 4′-chloro-2-nitro-1,1'-biphenyl, with a content of 98.69% and a yield of 90.2%.

[0063] Example 8:

[0064] This example provides a method for preparing a 2-nitro-1,1'-biphenyl compound of the present invention, which comprises the following steps:

[0065] In a 500 mL three-necked flask, 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 144.05 g of 1,2-dichloroethane were added. After stirring and dissolving, 1.20 g of manganese sulfate and 0.12 g of 4-dimethylaminopyridine were added. After heating to 30 °C, an aqueous solution of 428.94 g of calcium hypochlorite (mass fraction 10%) was added dropwise. After the addition was completed, the reaction was continued under warming for 3 h. After the reaction ended, liquid separation was carried out. The organic phase was washed with water, the solvent was removed, and recrystallization was carried out with methanol to obtain 21.70 g of a light yellow solid, 4′-chloro-2-nitro-1,1'-biphenyl, with a content of 98.06% and a yield of 91.3%.

[0066] Comparative Example 1

[0067] This comparative example provides a method for preparing a 2-nitro-1,1'-biphenyl compound of the present invention. Manganese acetate in Example 1 is not included in this comparative example, and the steps are as follows:

[0068] In a 500 mL three-necked flask, 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 96.03 g of dichloromethane were added. After stirring and dissolving, 0.24 g of tetrabutylammonium bromide was added. After heating to 30 °C, an aqueous solution of 148.88 g of sodium hypochlorite (mass fraction 15%) was added dropwise. After the addition was completed, the reaction was continued under warming for 4 h. After the reaction ended, liquid separation was carried out. The organic phase was washed with water, the solvent was removed, and recrystallization was carried out with methanol to obtain 15.38 g of a brownish-yellow solid, 4′-chloro-2-nitro-1,1'-biphenyl, with a content of 94.37% and a yield of 62.3%.

[0069] Comparative Example 2

[0070] This comparative example provides a method for preparing the 2-nitro-1,1'-biphenyl compound of the present invention. This comparative example does not include tetrabutylammonium bromide in Example 1, and the steps are as follows:

[0071] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 96.03 g of dichloromethane into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese acetate. After heating to 30 °C, add an aqueous solution of 148.88 g of sodium hypochlorite (mass fraction 15%) dropwise. After the addition is completed, continue the heat preservation reaction for 4 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, add methanol for recrystallization to obtain 21.04 g of yellow solid 4'-chloro-2-nitro-1,1'-biphenyl, with a content of 97.70% and a yield of 88.2%.

[0072] Comparative Example 3

[0073] This comparative example provides a method for preparing the 2-nitro-1,1'-biphenyl compound of the present invention. This comparative example does not include sodium hypochlorite in Example 1, and the steps are as follows:

[0074] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 96.03 g of dichloromethane into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese acetate and 0.24 g of tetrabutylammonium bromide. After heating to 30 °C, carry out the heat preservation reaction for 4 h. HPLC monitoring shows that no 4'-chloro-2-nitro-1,1'-biphenyl is formed.

[0075] Comparative Example 4

[0076] This comparative example provides a method for preparing the 2-nitro-1,1'-biphenyl compound of the present invention. In this comparative example, dichloromethane in Example 1 is replaced with chlorobenzene, and the other conditions are the same. The steps are as follows:

[0077] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 96.03 g of chlorobenzene into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese acetate and 0.24 g of tetrabutylammonium bromide. After heating to 100 °C, add an aqueous solution of 148.88 g of sodium hypochlorite (mass fraction 15%) dropwise. After the addition is completed, continue the heat preservation reaction for 4 h. After the reaction is completed, separate the layers. Wash the organic phase with water, remove the solvent, add methanol for recrystallization to obtain 14.84 g of brown solid 4'-chloro-2-nitro-1,1'-biphenyl, with a content of 91.67% and a yield of 58.4%.

[0078] Comparative Example 5

[0079] This comparative example provides a method for preparing the 2-nitro-1,1'-biphenyl compound of the present invention. In this comparative example, sodium hypochlorite in Example 1 is replaced with potassium permanganate, and the other conditions are the same. The steps are as follows:

[0080] Add 24.01 g (99%, 0.1 mol) of 4'-chloro-2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl and 96.03 g of dichloromethane into a 500 mL three-necked flask. After stirring and dissolving, add 0.24 g of manganese acetate and 0.24 g of tetrabutylammonium bromide. After heating to 30 °C, dropwise add an aqueous solution of 300 g of potassium permanganate (containing 23.7 g of potassium permanganate, 0.15 mol). After the dropping is completed, continue to keep the temperature for reaction for 2 h. After the reaction is completed, filter. The filtrate is separated into layers. The organic phase is washed with water, the solvent is removed, and methanol is added for recrystallization to obtain 15.68 g of a yellowish-brown solid 4'-chloro-2-nitro-1,1'-biphenyl, with a content of 93.78% and a yield of 63.1%.

[0081] The above has made a detailed description of the embodiments of the present invention. However, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge scope of those of ordinary skill in the art. In addition, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

Claims

1. A method for synthesizing 2-nitro-1,1'-biphenyl compounds, characterized in that, Using a 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound shown in Formula I as a raw material, a reaction is carried out in the presence of a catalyst, a solvent and an oxidant to obtain a 2-nitro-1,1'-biphenyl compound shown in Formula II. The reaction formula is as follows: R 1 、 R 2 、 R 3 、 R 4 and R 5 are each independently selected from hydrogen, fluorine, chlorine, bromine or an alkoxy group, and the alkoxy group is selected from methoxy, ethoxy, propoxy, isopropoxy or benzyloxy; The catalyst includes a manganese catalyst and a phase transfer catalyst; The oxidant includes an aqueous solution of hypochlorite; The manganese catalyst is at least one of manganese acetate, manganese acetylacetonate, manganese sulfate, manganese nitrate and manganese chloride; The phase transfer catalyst is at least one of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogensulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride and 4-dimethylaminopyridine; The aqueous solution of hypochlorite is at least one of an aqueous solution of sodium hypochlorite, an aqueous solution of potassium hypochlorite and an aqueous solution of calcium hypochlorite; The solvent is at least one of dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran and dioxane.

2. The synthesis method according to claim 1, wherein The mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the solvent is 1:2 to 6.

3. The synthesis method according to claim 1, characterized in that, The mass ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the manganese catalyst is 1:0.005 to 0.

1.

4. The synthesis method according to claim 1, wherein The molar ratio of the 2-nitro-1,2,3,6-tetrahydro-1,1'-biphenyl compound to the oxidant is 1:2 to 5.

5. The synthesis method according to claim 1, wherein The reaction time is 1 to 6 h, and the reaction temperature is 0 to 60 °C.

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