A non-column chromatography method for preparing 2h-indazole compounds from azobenzene compounds

Abstract

The application belongs to the technical field of organic compound preparation, and discloses a non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds. The non-column chromatography method comprises the following steps: mixing azobenzene compounds, diboate, water and an organic solvent, reacting, removing the organic solvent, extracting and recrystallizing to separate the 2H-indazole compounds. The reaction is carried out under sunlight, and the reaction time is less than 1 hour. In the method, the product separation and purification does not need to use a chromatography column. Moreover, the method has wide functional group compatibility, so that various types of azobenzene compounds can be converted into 2H-indazole compounds. From the time cost and economic cost, the method has significant advantages compared with the existing method, and does not use toxic silica gel powder.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic compound preparation, and particularly relates to a non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds. BACKGROUND

[0002] 2H-indazole compounds are important organic chemical raw materials, and are widely used in the fields of synthesizing various fine chemical products such as organic dyes, pigments, pesticides, medicines and functional materials. The methods for preparing 2H-indazole compounds mainly include the following types: (1) cross-coupling method of ortho-halogen-substituted benzaldehyde and phenylhydrazine; (2) 1,3-dipole cycloaddition method of diazo compound; and (3) C-H bond amination synthesis method of phenylhydrazone.

[0003] There are many methods for synthesizing 2H-indazole compounds reported in the past, which generally need to use noble metal catalysis or need expensive ligands. Such methods are not only environmentally unfriendly, but also have high cost, and are difficult to be applied to industrial production. At present, there are also attempts to synthesize 2H-indazole compounds by using non-metal catalysis, but a large amount of additives are usually used to assist the reaction, which does not meet the requirements of atom economy.

[0004] In the prior art, a column chromatography separation and purification method is also used to prepare and separate 2H-indazole compounds, but the method needs a long time, a large number of reagents, and even toxic silica gel powder is used, and the economic cost is high.

[0005] Therefore, it is urgent to provide a new method for preparing 2H-indazole compounds, which has short time, low economic cost, does not need to use toxic silica gel powder, has high product yield, and has short reaction time. SUMMARY

[0006] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application provides a non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds. The non-column chromatography method has short time, low economic cost, does not need to use toxic silica gel powder, has high product yield, and has short reaction time. The non-column chromatography method of the present application has significant advantages compared with the existing methods in terms of time cost and economic cost.

[0007] In addition, the non-column chromatography method of the present application not only does not need to use metal catalysts, but also does not need to be heated, and only needs sunlight at room temperature, has short reaction time (less than 1 hour, even not more than 30 minutes), high product yield, and does not need to use column chromatography method for product separation and purification.

[0008] The inventive concept of the present application is that the present application uses azobenzene compounds as raw materials, water as hydrogen source, and adds diboronic acid ester to prepare 2H-indazole compound products with a yield of not less than 90% in a reaction time of less than 1 hour (even less than 30 minutes) under sunlight without metal catalyst. Moreover, the non-column chromatography method of the present application shows wide functional group compatibility, so that various types of azobenzene compounds can be converted into 2H-indazole compounds.

[0009] In addition, green chemistry index analysis shows that the atomic economy of the non-column chromatography method of the present application is more than 50%, even reaching 52%, safe solvents and auxiliaries are used, renewable raw materials are used, no harmful by-products are generated, no ecological toxicity is generated, the carbon efficiency is more than 60%, for example, reaching 61%, the reaction mass efficiency is more than 51%, for example, reaching 52%, and it is a green and efficient 2H-indazole compound synthesis method.

[0010] Economic cost comparison and analysis, preparation of the same amount of 2H-indazole compound, preparation of 20 mmol For example, only the separation and purification conditions are different, if the product is separated and purified by column chromatography method, the time cost is about 2 hours, about 500 mL of n-hexane / ethyl acetate eluent is consumed, 50-100 g of 300-400 mesh silica gel powder is consumed, the comprehensive material cost is about 100 yuan RMB, and the use of silica gel powder is harmful to human body, while the separation and purification time of the non-column chromatography method of the present application is less than 0.5 hour, the solvent used is less than 20 mL and a small amount of sodium hydroxide solution, and the comprehensive material cost is less than 10 yuan RMB. Compared with the column chromatography separation and purification method, the present application saves more than 90% of the cost of separation and purification materials, and avoids the use of harmful silica gel powder.

[0011] Specifically, a non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds comprises the following steps:

[0012] The azobenzene compound, diboronic acid ester, water and organic solvent are mixed, reacted, the organic solvent is removed, extracted, and recrystallized to separate the 2H-indazole compound;

[0013] The reaction is carried out under sunlight;

[0014] The reaction time is less than 1 hour.

[0015] Preferably, the reaction time is not more than 30 minutes.

[0016] Preferably, the extraction is carried out using at least one of tetrahydrofuran (THF), acetonitrile (MeCN), methanol (MeOH) or dichloromethane (DCM); further preferably, the extraction is carried out using dichloromethane (DCM).

[0017] Preferably, after the extraction, the product is washed with a base solution, such as sodium hydroxide solution.

[0018] Preferably, after the base solution washing, the product is dried and then concentrated under reduced pressure and recrystallized.

[0019] Preferably, the azobenzene compound has a general structure of Ar 1 -N=N-Ar 2 wherein Ar 1 and Ar 2 each independently represents an aryl group or a substituted aryl group.

[0020] Preferably, the aryl group is an aromatic ring with 6-16 carbon atoms; further preferably, the aryl group is an aromatic ring with 6-12 carbon atoms.

[0021] Further preferably, the aryl group is selected from at least one of phenyl and naphthyl.

[0022] Preferably, the substitution is by at least one of alkyl, alkenyl, alkynyl, aryl, halogen, nitro, alkoxy, ester, sulfonamide, cyano, carbonyl, trifluoromethyl. The number of substitutions ranges from mono-substitution to the maximum number of substitutions.

[0023] Preferably, the alkyl and alkoxy groups have 1-15 carbon atoms; further preferably, the alkyl and alkoxy groups have 2-12 carbon atoms.

[0024] Preferably, the azobenzene compound is selected from any one of the following:

[0025]

[0026] Preferably, the 2H-indazole compound is selected from any one of the following:

[0027]

[0028] Preferably, the bisboronic acid ester is selected from biscatechol boronic acid ester (bisboronic acid ester is abbreviated as B2cat2. The structure is ).

[0029] Preferably, the organic solvent is selected from at least one of tetrahydrofuran (THF), acetonitrile (MeCN), methanol (MeOH), or dichloromethane (DCM); further preferably, the organic solvent is dichloromethane (DCM).

[0030] Preferably, the molar ratio of the azobenzene compound, the diboronate, and water is 1:(0.5-4.8):(10-100); more preferably, the molar ratio of the azobenzene compound, the diboronate, and water is 1:(1-1.8):(10-50).

[0031] Preferably, the amount ratio of the azobenzene compound to the organic solvent is 0.1 mmol:0.5-4.5 mL; preferably, 0.1 mmol:0.5-1 mL.

[0032] Preferably, the mixing process is simultaneous mixing of the components or stepwise mixing.

[0033] Preferably, the reaction is carried out at normal temperature and pressure in an atmospheric environment by mixing the components and irradiating with light.

[0034] Preferably, the solvent is removed by rotary evaporation.

[0035] The second aspect of the present application is the use of the above-mentioned non-column chromatography method.

[0036] In particular, the above-mentioned non-column chromatography method is used in the field of organic synthesis.

[0037] Preferably, the field of organic synthesis includes the field of synthesis of organic dyes, pigments, pesticides, pharmaceuticals, or functional materials.

[0038] Compared with the prior art, the present application has the following advantages:

[0039] (1) The present application uses an azobenzene compound as a raw material, water as a hydrogen source, and a diboronate, and the reaction is carried out under sunlight irradiation without a metal catalyst, and a 2H-indazole compound product with a yield of not less than 90% can be obtained in less than 1 hour. In the method of the present application, the product does not need to be separated and purified using a chromatography column. Moreover, the method of the present application shows wide functional group compatibility, so that various types of azobenzene compounds can be converted into 2H-indazole compounds.

[0040] (2) The non-column chromatography method of the present application has significant advantages in terms of time cost and economic cost compared with the prior art, and does not use toxic silica gel powder. DETAILED DESCRIPTION

[0041] In order to make those skilled in the art more clearly understand the technical solutions of the present application, the following examples are given for illustration. It should be pointed out that the following examples do not limit the scope of protection required by the present application.

[0042] The starting materials, reagents or apparatuses used in the following examples, if not specifically stated, are either commercially available or are prepared by known methods. The term "about" of the present application means a fluctuation of 0.2%.

[0043] Example 1: Preparation of 2,3-diphenyl-2H-indazole

[0044] The reaction equation involved in the preparation of 2,3-diphenyl-2H-indazole (only the target product is embodied in the reaction equation) is as follows:

[0045]

[0046] A non-column chromatography method for preparing 2H-indazole compounds from an azobenzene compound includes the following steps:

[0047] At normal temperature and pressure, 0.2 mol of bis-catechol borate (B2cat2), 1.5 mL of dichloromethane (DCM) organic solvent, 0.2 mmol of 2-benzoyl azobenzene, and 0.1 mL of water are sequentially added to a 10 mL quartz test tube equipped with a stirrer, mixed to obtain a mixture, the test tube is sealed, and the reaction is stirred under sunlight for 30 minutes. The light is stopped, and a reaction mixture is obtained. The reaction mixture is extracted with DCM (the amount of DCM used is 4 mL), washed with sodium hydroxide solution (the amount used is 2 mL, and the concentration is 0.1 mol / L) for 3 times, the obtained organic phase is combined, dried with anhydrous sodium sulfate (the amount used is 3 g), concentrated under reduced pressure, and recrystallized (the process from extraction to completion of recrystallization takes about 0.5 hours), to obtain the product 2,3-diphenyl-2H-indazole. The yield of 2,3-diphenyl-2H-indazole is 99% (yield = actual yield / theoretical yield * 100%).

[0048] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 2,3-diphenyl-2H-indazole prepared in Example 1 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.84-7.82 (d, 1H), 7.76-7.73 (d, 1H), 7.48-7.38 (m, 11H), 7.19-7.15 (q, 1H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 149.02, 140.28, 135.42, 129.96, 129.70, 128.97, 128.76, 128.31, 128.25, 126.98, 126.04, 122.51, 121.77, 120.51, 117.78.

[0049] Example 2: Preparation of 3-(2-ethylphenyl)-2-phenyl-2H-indazole

[0050] The reaction equation involved in the preparation of 3-(2-ethylphenyl)-2-phenyl-2H-indazole (only the target product is embodied in the reaction equation) is as follows:

[0051]

[0052] A non-column chromatography method for preparing 2H-indazole compounds from an azobenzene compound includes the following steps:

[0053] At normal temperature and pressure, 0.2 mol of bis-catechol borate (B2cat2), 1.5 mL of dichloromethane as an organic solvent, 0.2 mmol of 2-(2-ethylbenzoyl) azobenzene, and 0.1 mL of water are sequentially added to a 10 mL quartz test tube equipped with a stirrer, mixed, the sealed test tube is taken out of the glove box, and placed under sunlight for stirring reaction for 30 minutes. After stopping the light, a reaction mixture is obtained. The reaction mixture is extracted with DCM and washed with sodium hydroxide solution for 3 times. The obtained organic phase is combined, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized to obtain the product 3-(2-ethylphenyl)-2-phenyl-2H-indazole. The yield of 3-(2-ethylphenyl)-2-phenyl-2H-indazole is 95%.

[0054] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 3-(2-ethylphenyl)-2-phenyl-2H-indazole prepared in Example 2 are as follows: 1 H-NMR (CDCl3, 400MHz δ (ppm) 7.85 (d, J = 8.8 Hz, 1H), 7.50-7.29 (m, 11H), 7.14-7.08 (m, 1H), 2.32 (dp, J = 22.1, 7.4 Hz, 2H), 0.91 (t, J = 7.6 Hz, 3H). 13 C-NMR (CDCl3, 125MHz) δ (ppm) 148.75, 143.83, 140.37, 135.25, 131.40, 129.55, 128.98, 128.88, 128.84, 127.88, 127.02, 126.02, 124.89, 122.91, 122.09, 120.72, 117.65, 26.00, 14.48.

[0055] Example 3: 3-(2-methoxyphenyl)-2-phenyl-2H-indazole

[0056] The reaction equation involved in the preparation of 3-(2-methoxyphenyl)-2-phenyl-2H-indazole (only the target product is embodied in the reaction equation) is as follows:

[0057]

[0058] A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds, comprising the following steps:

[0059] At normal temperature and pressure, 0.2 mol of bis-catechol borate (B2cat2), 1.5 mL of dichloromethane, 0.2 mmol of 2-(2-ethylbenzoyl) azobenzene, and 0.1 mL of water were sequentially added to a 10 mL quartz test tube equipped with a stirrer, mixed, and a mixture was obtained. The sealed test tube was removed from the glove box and placed under sunlight for stirring reaction for 30 minutes. The light was stopped, and a reaction mixture was obtained. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution 3 times. The obtained organic phase was combined, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized to obtain the product 3-(2-methoxyphenyl)-2-phenyl-2H-indazole. The yield of 3-(2-methoxyphenyl)-2-phenyl-2H-indazole was 99%, and the yield of the column chromatography method was 99%.

[0060] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 3-(2-methoxyphenyl)-2-phenyl-2H-indazole prepared in Example 3 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.84 (dd, J = 8.7, 5.5 Hz, 1H), 7.65-7.59 (m, 1H), 7.51-7.32 (m, 8H), 7.16-7.07 (m, 2H), 6.88 (dd, J = 7.9, 5.7 Hz, 1H), 3.37 (d, J = 5.6 Hz, 3H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 156.75, 148.97, 141.41, 132.53, 131.68, 130.64, 128.60, 127.72, 126.74, 124.58, 122.59, 121.99, 120.89, 120.75, 119.15, 117.71, 111.51, 54.83.

[0061] Example 4: Preparation of 3-(2-naphthyl)-2-phenyl-2H-indazole

[0062] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 3-(2-naphthyl)-2-phenyl-2H-indazole is as follows:

[0063]

[0064] A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds, comprising the following steps:

[0065] To a 10 mL quartz test tube equipped with a stirrer, 0.2 mmol of 2-(2-naphthoyl) azobenzene, 0.1 mL of water were added at room temperature and normal pressure, and then 1.5 mL of dichloromethane was added. The mixture was mixed, the test tube was sealed, and the mixture was stirred under sunlight for 30 minutes. The reaction was stopped, and the reaction mixture was extracted with DCM and washed with sodium hydroxide solution three times. The obtained organic phase was combined, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized to obtain the product 3-(2-naphthyl)-2-phenyl-2H-indazole. The yield of 3-(2-naphthyl)-2-phenyl-2H-indazole was 99%, and the yield of column chromatography was 99%.

[0066] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 3-(2-naphthyl)-2-phenyl-2H-indazole prepared in Example 4 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 8.03 (s, 1H), 7.85 (dd, J = 22.8, 8.2 Hz, 5H), 7.61-7.48 (m, 4H), 7.48-7.36 (m, 4H), 7.33 (d, J = 8.5 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 149.12, 140.29, 135.38, 133.31, 132.79, 129.08, 129.06, 128.45, 128.33, 128.25, 127.82, 127.39, 127.11, 127.00, 126.89, 126.69, 126.03, 122.70, 122.06, 120.58, 117.87.

[0067] Example 5: 2-phenyl-3-(4-(phenyl ethynyl) phenyl)-2H-indazole

[0068] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 2-phenyl-3-(4-(phenyl ethynyl) phenyl)-2H-indazole is as follows:

[0069]

[0070] A non-column chromatography method for preparing 2H-indazole compounds from an azobenzene compound includes the following steps:

[0071] Into a 10 mL quartz test tube equipped with a stirrer, 0.2 mmol of 2-(4-(phenylethynyl)benzoyl) azobenzene, 0.1 mL of water were added successively at room temperature and normal pressure. The mixture was mixed and the test tube was sealed. The mixture was stirred under sunlight for 30 minutes. The light was stopped and a reaction mixture was obtained. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution three times. The obtained organic phase was combined and dried with anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and recrystallized to obtain the product 2-phenyl-3-(4-(phenylethynyl)phenyl)-2H-indazole. The yield of 2-phenyl-3-(4-(phenylethynyl)phenyl)-2H-indazole was 99% and the yield of the product by column chromatography was 99%.

[0072] The nuclear magnetic resonance hydrogen spectrum and the nuclear magnetic resonance carbon spectrum characterization results of the product 2-phenyl-3-(4-(phenylethynyl)phenyl)-2H-indazole prepared in Example 5 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.85 (dd, J = 8.8, 1.8 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.57 (dtd, J = 5.9, 3.4, 2.0 Hz, 4H), 7.49-7.36 (m, 11H), 7.23-7.17 (m, 1H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 149.07, 140.13, 134.67, 131.97, 131.66, 129.66, 129.53, 129.15, 128.55, 128.46, 128.43, 127.11, 126.06, 123.25, 122.96, 122.88, 121.78, 120.33, 117.92, 90.94, 88.86.

[0073] Example 6: 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole

[0074] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole is as follows:

[0075]

[0076] A non-column chromatography method for preparing 2H-indazole compounds from an azobenzene compound includes the following steps:

[0077] To a 10 mL quartz test tube equipped with a stirrer, 0.2 mmol of 2-(2,4-difluorobenzoyl) azobenzene, 0.1 mL of water were added at room temperature and normal pressure, and then mixed to obtain a mixture. The test tube was sealed and placed under sunlight for stirring reaction for 30 minutes. After stopping the light, a reaction mixture was obtained. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution for 3 times. The obtained organic phase was combined and dried with anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized to obtain the product 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole. The yield of 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole was 99%, and the yield of column chromatography was 98%.

[0078] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole prepared in Example 6 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.86 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.48-7.35 (m, 7H), 7.18 (t, J = 7.5 Hz, 1H), 6.99 (t, J = 8.2 Hz, 1H), 6.91 (t, J = 9.2 Hz, 1H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 164.80, 164.66, 162.26, 162.13, 161.27, 161.14, 158.75, 158.63, 148.96, 140.25, 132.84, 132.79, 132.75, 129.08, 128.62, 128.45, 127.05, 125.18, 122.85, 122.72, 120.06, 118.00, 114.46, 114.30, 112.18, 112.15, 111.97, 111.93, 105.22, 104.96, 104.71.

[0079] Example 7: 5-chloro-2,3-diphenyl-2H-indazole

[0080] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 5-chloro-2,3-diphenyl-2H-indazole is as follows:

[0081]

[0082] A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds includes the following steps:

[0083] To a 10 mL quartz test tube equipped with a stirrer, 0.2 mol of bis-catechol borate (B2cat2), 1.5 mL of dichloromethane, 0.2 mmol of 4-chloro-2-benzoyl azobenzene, 0.1 mL of water were added successively at room temperature and normal pressure. The mixture was mixed and the test tube was sealed. The mixture was stirred under sunlight for 30 minutes. The light was stopped and the reaction mixture was obtained. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution for 3 times. The obtained organic phase was combined and dried with anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and recrystallized to obtain the product 5-chloro-2,3-diphenyl-2H-indazole. The yield of 5-chloro-2,3-diphenyl-2H-indazole was 99% and the yield of column chromatography was 99%.

[0084] The nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum characterization results of the product 5-chloro-2,3-diphenyl-2H-indazole prepared in Example 7 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.82-7.66 (m, 2H), 7.51-7.28 (m, 11H) 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 147.31, 139.96, 135.22, 129.58, 129.37, 129.07, 128.92, 128.63, 128.51, 128.40, 128.19, 125.91, 122.18, 119.39, 119.26.

[0085] Example 8: 7-ethyl-2,3-diphenyl-2H-indazole

[0086] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 7-ethyl-2,3-diphenyl-2H-indazole is as follows:

[0087]

[0088] A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds includes the following steps:

[0089] To a 10 mL quartz test tube fitted with a stir bar, 0.2 mmol of 2,3-diphenyl-7-iodo-2H-indazole, 0.2 mmol of 2-chloro-5-benzoyl azobenzene, 0.1 mL of water, 1.5 mL of dichloromethane were added in that order at room temperature and normal pressure. The mixture was mixed and the test tube was sealed. The mixture was stirred under sunlight for 30 minutes. The light was stopped and the reaction mixture was obtained. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution three times. The obtained organic phase was combined and dried with anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and recrystallized to obtain the product 7-ethyl-2,3-diphenyl-2H-indazole. The yield of 7-ethyl-2,3-diphenyl-2H-indazole was 99% and the yield of column chromatography was 99%.

[0090] The results of the nuclear magnetic resonance hydrogen spectrum and the nuclear magnetic resonance carbon spectrum of the product 7-ethyl-2,3-diphenyl-2H-indazole prepared in Example 8 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.60 (t, J = 8.1 Hz, 1H), 7.53-7.46 (m, 2H), 7.46-7.33 (m, 8H), 7.25-7.08 (m, 2H), 3.19 (q, J = 7.5 Hz, 2H), 1.50 (t, J = 7.5 Hz, 3H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 148.60, 140.40, 135.62, 133.95, 130.21, 129.72, 129.00, 128.69, 128.19, 128.17, 126.29, 123.86, 122.93, 121.74, 117.92, 24.32, 13.92.

[0091] Example 9: 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole

[0092] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole is as follows:

[0093]

[0094] A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds includes the following steps:

[0095] To a 10 mL quartz test tube equipped with a stirrer, 0.2 mmol of 2,3-diphenyl-2H-indazole, 0.2 mmol of 2-methoxy-5-benzoyl azobenzene, 0.1 mL of water were added successively at room temperature and normal pressure. The mixture was mixed and the test tube was sealed. The mixture was stirred under sunlight for 30 minutes. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution three times. The obtained organic phase was combined and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and recrystallized to obtain the product 2,3-diphenyl-2H-indazole. The yield of 2,3-diphenyl-2H-indazole was 99% and the yield of 2,3-diphenyl-2H-indazole by column chromatography was 99%.

[0096] The results of the nuclear magnetic resonance hydrogen spectrum and the nuclear magnetic resonance carbon spectrum of the product 2,3-diphenyl-2H-indazole prepared in Example 9 are as follows: 1 H-NMR (CDCI3, 400 MHz δ (ppm) 7.66 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 24.0 Hz, 7H), 7.26 (d, J = 7.9 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 6.66 (d, J = 7.1 Hz, 1H), 4.05 (s, 3H); 13 C-NMR (CDCI3, 125 MHz) δ (ppm) 150.57, 142.60, 139.59, 134.51, 133.24, 132.46, 129.98, 129.19, 128.86, 126.26, 124.52, 123.44, 118.39, 111.71, 111.39, 103.66, 55.58.

[0097] Comparative Example 1

[0098] The reaction equation (only the target product is represented in the reaction equation) involved in the preparation of 2,3-diphenyl-2H-indazole is as follows:

[0099]

[0100] The method for preparing diphenylhydrazine or 2H-indazole compounds using azobenzene compounds includes the following steps:

[0101] In a glove box under nitrogen atmosphere, 0.3 mmol of bis-catechol borate (B2cat2), 1.5 mL of organic solvent tetrahydrofuran, 0.2 mmol of 2-benzoyl azobenzene, 0.1 mL of water were sequentially added into a 10 mL quartz test tube with a stirrer, mixed to obtain a mixture, the sealed test tube was taken out of the glove box, and placed under 450 nm light to stir for 30 minutes, then the organic solvent was removed under reduced pressure, and the product was separated and purified by column chromatography. The developing agent used in the separation and purification process was a mixture of n-hexane / ethyl acetate (volume ratio of 15:1). During the column chromatography separation and purification process, about 500 mL of n-hexane / ethyl acetate eluent, 80 g of 300-400 mesh silica gel powder were consumed, and the column chromatography separation and purification process took about 2 hours. The isolated product was 2,3-diphenyl-2H-indazole.

[0102] Example 1 and Comparative Example 1 were each prepared at a scale of 20 mmol The time cost and economic cost were compared and analyzed:

[0103] Comparative Example 1 used column chromatography to separate and purify the product, which required a time cost of about 2 hours, consumed about 500 mL of n-hexane / ethyl acetate eluent, 80 g of 300-400 mesh silica gel powder, and the comprehensive material cost was about 100 yuan RMB (20 mmol, 5.4 g of product). In addition, the use of silica gel powder is harmful to the human body.

[0104] The non-column chromatography method of Example 1 used extraction and recrystallization to separate and purify the product, which took about 0.5 hours, used less than 20 mL of DCM solvent and a small amount of sodium hydroxide solution, and the comprehensive material cost was less than 10 yuan RMB. Compared with the column chromatography separation and purification method of Comparative Example 1, the Example 1 of the present application saved more than 90% of the cost of the material for separation and purification, avoided the use of harmful silica gel powder, and saved 75% of the separation and purification time.

[0105] In the process of extracting and recrystallizing the product, other embodiments of the present application are similar to Example 1 in terms of time cost and economic cost, and are significantly better than the time cost and economic cost required for separating and purifying the product by column chromatography.

Claims

1. A non-column chromatography method for preparing a 2H-indazole compound from an azobenzene compound, characterized by, The method comprises the following steps: The azobenzene compound, the bis-o-benzene borate, water and an organic solvent are mixed, and the reaction is carried out under sunlight; the organic solvent is removed; the reaction mixture is extracted with dichloromethane, washed with a sodium hydroxide solution, combined, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized to obtain the 2H-indazole compound. The azobenzene compound is The 2H-indazole compound is The bisboronic acid ester is bis-o-catechol boronic acid ester; and the organic solvent is dichloromethane. The molar ratio of the azobenzene compound, the bis-borate and water is 1:(1-1.8):(10-50), and the ratio of the azobenzene compound to the organic solvent is 0.1 mmol:(0.5-1) mL; the concentration of the sodium hydroxide solution is 0.1 mol / L. The reaction time is less than 1 hour.

2. The non-column chromatography method according to claim 1, characterized in that, The reaction time is not more than 30 minutes.

3. The non-column chromatography method according to claim 1, characterized in that, The organic solvent is removed by a rotary evaporation method.

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