Non-column chromatography method for preparing 2H-indazole compound from azobenzene compound

Abstract

The invention belongs to the technical field of preparation of organic compounds, 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 an azobenzene compound, biborate, water and an organic solvent, reacting, removing the organic solvent, extracting, recrystallizing and separating to obtain the 2H-indazole compound, the reaction is carried out under sunlight; the reaction time is less than 1 hour. In the method, the separation and purification of the product do not need to use a chromatographic column. Moreover, the method disclosed by the invention shows wide functional group compatibility, so that various types of azobenzene compounds can be converted into 2H-indazole compounds. And compared with the existing method, the method has obvious advantages in terms of time cost and economic cost, and toxic silica gel powder is not used.

Description

Technical Field

[0001] The invention 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 Art

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

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

[0004] The prior art also records the use of column chromatography separation and purification methods to prepare and separate 2H-indazole compounds. However, this method requires a long time, uses many types of reagents, and even uses toxic silica gel powder when separating and purifying 2H-indazole compounds, which has high economic costs.

[0005] Therefore, there is an urgent need to provide a new preparation method for 2H-indazole compounds, which method requires short time, has low economic cost, does not require the use of toxic silica gel powder, has high product yield, and has a short reaction time. Summary of the invention

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

[0007] In addition, the non-column chromatography method of the present invention not only does not require the use of metal catalysts, but also does not require heating. Under normal temperature conditions, only sunlight illumination is required, the reaction time is short (less than 1 hour, or even no more than 30 minutes), the product yield is high, and the separation and purification of the product does not require the use of column chromatography.

[0008] The inventive concept of the present invention is: the present invention uses azobenzene compounds as raw materials, uses water as a hydrogen source, adds biboric acid ester, and in the absence of a metal catalyst, the reaction time is within 1 hour (even within 30 minutes) under sunlight illumination, and a 2H-indazole compound product with a yield of not less than 90% can be obtained. In addition, the non-column chromatography method of the present invention exhibits a wide range of functional group compatibility, so that various types of azobenzene compounds can be converted into 2H-indazole compounds.

[0009] In addition, green chemical index analysis shows that the atomic economy of the non-column chromatography method of the present invention exceeds 50%, even reaching 52%, uses safe solvents and additives, uses renewable raw materials, does not produce harmful derivatives, has no eco-toxicity, has a carbon efficiency of more than 60%, for example, reaching 61%, and a reaction mass efficiency of more than 51%, for example, reaching 52%. It is a green and efficient method for synthesizing 2H-indazole compounds.

[0010] Comparative analysis of economic costs, preparing the same amount of 2H-indazole compounds to prepare 20mmol For example, only the separation and purification conditions are different. If the product is separated and purified by column chromatography, the time cost invested 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, and the comprehensive material cost is about 100 yuan, and the use of silica gel powder is harmful to the human body. The non-column chromatography method of the present invention requires the separation and purification time of the product to be less than 0.5 hours, and 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. Compared with the column chromatography separation and purification method, the present invention 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, biboric acid ester, water and an organic solvent are mixed, reacted, the organic solvent is removed, extracted, and recrystallized to separate and obtain 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 does not exceed 30 minutes.

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

[0017] Preferably, after the extraction, washing is performed with an alkaline solution, such as a sodium hydroxide solution.

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

[0019] Preferably, the azobenzene compound has the general structural formula of Ar 1 -N=N-Ar 2 , among which 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] More preferably, the aryl group is selected from at least one of phenyl and naphthyl.

[0022] Preferably, the substitution refers to substitution by at least one of alkyl, alkenyl, alkynyl, aryl, halide, nitro, alkoxy, ester, sulfonamide, cyano, carbonyl, and trifluoromethyl. The number of substitutions ranges from single substitution to maximum number of substitutions.

[0023] Preferably, the carbon number of the alkyl group or alkoxy group is 1-15; further preferably, the carbon number of the alkyl group or alkoxy group is 2-12.

[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 biboric acid ester is selected from bis-bis-catechol borate (bis-bis-catechol borate 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 diboric acid ester and water is 1:(0.5-4.8):(10-100); more preferably, the molar ratio of the azobenzene compound, the diboric acid ester and water is 1:(1-1.8):(10-50).

[0031] Preferably, the 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 that the components are mixed simultaneously or in steps.

[0033] Preferably, the reaction is carried out at room temperature, pressure and 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 invention is the application of the above non-column chromatography method.

[0036] Specifically, the application of the above non-column chromatography method in the field of organic synthesis.

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

[0038] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0039] (1) The present invention uses an azobenzene compound as a raw material, water as a hydrogen source, and a diboric acid ester. In the absence of a metal catalyst, the reaction is carried out under sunlight. After a reaction time of less than 1 hour, a 2H-indazole compound product with a yield of not less than 90% can be obtained. In the method of the present invention, the separation and purification of the product does not require the use of a chromatography column. In addition, the method of the present invention exhibits a wide range of 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 invention has significant advantages over existing methods in terms of both time cost and economic cost, and does not use toxic silica gel powder. DETAILED DESCRIPTION

[0041] In order to make the technical scheme of the present invention more clearly understood by those skilled in the art, the following embodiments are listed for illustration. It should be pointed out that the following embodiments do not limit the protection scope of the present invention.

[0042] Unless otherwise specified, the raw materials, reagents or devices used in the following examples can be obtained from conventional commercial sources or by existing known methods. "About" in the present invention means a fluctuation within 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 reflected in the reaction equation) is as follows:

[0045]

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

[0047] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)-1-diol) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane (DCM), 0.2 mmol of 2-benzoyl azobenzene, and 0.1 mL of water were added to a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed and placed under sunlight for stirring and reaction for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM (the amount of DCM was 4 mL), and washed 3 times with a sodium hydroxide solution (the amount was 2 mL, and the concentration was 0.1 mol / L). The obtained organic phases were combined, dried with anhydrous sodium sulfate (the amount was 3 g), concentrated under reduced pressure, and recrystallized (the process from extraction to completion of recrystallization took about 0.5 hours) to obtain the product 2,3-diphenyl-2H-indazole, and the yield of 2,3-diphenyl-2H-indazole was 99% (yield = actual yield / theoretical yield*100%).

[0048] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 2,3-diphenyl-2H-indazole prepared in this Example 1 are as follows: 1 H-NMR (CDCl3, 400MHz 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(CDCl3,125MHz)δ(ppm)149.02,140.28,135.42,129.96,129.70,128.9 7,128.76,128.31,128.25,126.98,126.04,122.51,121.77,120.51,117.78.

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

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

[0051]

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

[0053] At room temperature and pressure, 0.2 mol of bis(bis(pyrocatechol) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-(2-ethylbenzoyl)azobenzene, and 0.1 mL of water were added sequentially into a 10 mL quartz test tube equipped with a stirring bar, and the mixture was mixed to obtain a mixture. The sealed test tube was taken out from the glove box, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over 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 was 95%.

[0054] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance 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 = 8.8Hz, 1H), 7.50–7.29 (m, 11H), 7.14–7.08 (m, 1H), 2.32 (dp, J = 22.1, 7.4Hz, 2H), 0.91 (t, J = 7.6Hz, 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 preparing 3-(2-methoxyphenyl)-2-phenyl-2H-indazole (only the target product is reflected in the reaction equation) is as follows:

[0057]

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

[0059] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-(2-ethylbenzoyl)azobenzene, and 0.1 mL of water were added sequentially into a 10 mL quartz test tube equipped with a stirrer, and the mixture was mixed to obtain a mixture. The sealed test tube was taken out from the glove box, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over 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 hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 3-(2-methoxyphenyl)-2-phenyl-2H-indazole prepared in Example 3 are as follows: 1 H-NMR(CDCl3,400MHzδ(ppm)7.84(dd,J=8.7,5.5Hz,1H),7.65–7.59(m,1H),7.51– 7.32(m,8H),7.16–7.07(m,2H),6.88(dd,J=7.9,5.7Hz,1H),3.37(d,J=5.6Hz,3H); 13 C-NMR(CDCl3,125MHz)δ(ppm)156.75,148.97,141.41,132.53,131.68,130.64,128.60,1 27.72,126.74,124.58,122.59,121.99,120.89,120.75,119.15,117.71,111.51,54.83.

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

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

[0063]

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

[0065] At room temperature and pressure, 0.2 mol of bis(bis(phthalic acid)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-(2-naphthoyl)azobenzene, and 0.1 mL of water were added into a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over 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 the column chromatography method was 99%.

[0066] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 3-(2-naphthyl)-2-phenyl-2H-indazole prepared in this Example 4 are as follows: 1 H-NMR (CDCl3, 400MHz δ (ppm) 8.03 (s, 1H), 7.85 (dd, J = 22.8, 8.2Hz, 5H), 7.61– 7.48(m,4H),7.48–7.36(m,4H),7.33(d,J=8.5Hz,1H),7.20(t,J=7.5Hz,1H); 13 C-NMR(CDCl3,125MHz)δ(ppm)149.12,140.29,135.38,133.31,132.79,129.08,129.06,128.45,128.3 3,128.25,127.82,127.39,127.11,127.00,126.89,126.69,126.03,122.70,122.06,120.58,117.87.

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

[0068] The reaction equation involved in preparing 2-phenyl-3-(4-(phenylethynyl)phenyl)-2H-indazole (only the target product is reflected in the reaction equation) is as follows:

[0069]

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

[0071] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-(4-(phenylethynyl)benzoyl)azobenzene, and 0.1 mL of water were added sequentially into a 10 mL quartz test tube equipped with a stirring bar, and the mixture was mixed to obtain a mixture. The test tube was sealed, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over anhydrous sodium sulfate, 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 column chromatography method was 99%.

[0072] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 2-phenyl-3-(4-(phenylethynyl)phenyl)-2H-indazole prepared in this Example 5 are as follows: 1 H-NMR(CDCl3,400MHzδ(ppm)7.85(dd,J=8.8,1.8Hz,1H),7.76(d,J=8.5Hz,1 H),7.57(dtd,J=5.9,3.4,2.0Hz,4H),7.49–7.36(m,11H),7.23–7.17(m,1H); 13 C-NMR (CDCl3, 125MHz) 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 involved in preparing 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole (only the target product is reflected in the reaction equation) is as follows:

[0075]

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

[0077] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-(2,4-difluorobenzoyl)azobenzene, and 0.1 mL of water were added to a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over 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 the column chromatography method was 98%.

[0078] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 3-(2,4-difluorophenyl)-2-phenyl-2H-indazole prepared in Example 6 are as follows: 1 H-NMR(CDCl3,400MHzδ(ppm)7.86(d,J=8.8Hz,1H),7.58(d,J=8.5Hz,1H),7.48– 7.35(m,7H),7.18(t,J=7.5Hz,1H),6.99(t,J=8.2Hz,1H),6.91(t,J=9.2Hz,1H); 13 C-NMR(CDCl3,125MHz)δ(ppm)164.80,164.66,162.26,162.13,161.27,161.14,158.75,158.63,148.96,140.25,132.84,132.79,132.75,129.0 8,128.62,128.45,127.05,125.18,122.85,122.72,120.06,118.00,11 4.46,114.30,112.18,112.15,111.97,111.93,105.22,104.96,104.71.

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

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

[0081]

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

[0083] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 4-chloro-2-benzoylazobenzene, and 0.1 mL of water were added to a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed three times with a sodium hydroxide solution. The obtained organic phases were combined, dried over anhydrous sodium sulfate, 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 the column chromatography method was 99%.

[0084] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 5-chloro-2,3-diphenyl-2H-indazole prepared in Example 7 are as follows: 1 H-NMR(CDCl3,400MHzδ(ppm)7.82–7.66(m,2H),7.51–7.28(m,11H) 13 C-NMR(CDCl3,125MHz)δ(ppm)147.31,139.96,135.22,129.58,129.37,129.0 7,128.92,128.63,128.51,128.40,128.19,125.91,122.18,119.39,119.26.

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

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

[0087]

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

[0089] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-chloro-5-benzoylazobenzene, and 0.1 mL of water were added into a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed, and the mixture was stirred and reacted under sunlight for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM, and the mixture was washed with sodium hydroxide solution for 3 times. The obtained organic phases were combined, dried over anhydrous sodium sulfate, 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 the column chromatography method was 99%.

[0090] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 7-ethyl-2,3-diphenyl-2H-indazole prepared in Example 8 are as follows: 1 H-NMR(CDCl3,400MHzδ(ppm)7.60(t,J=8.1Hz,1H),7.53–7.46(m,2H),7.46– 7.33(m,8H),7.25–7.08(m,2H),3.19(q,J=7.5Hz,2H),1.50(t,J=7.5Hz,3H); 13 C-NMR (CDCl3, 125MHz) 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 involved in preparing 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole (only the target product is reflected in the reaction equation) is as follows:

[0093]

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

[0095] At room temperature and pressure, 0.2 mol of bis(bis(cyclopentyl)benzene) borate (B2cat2), 1.5 mL of an organic solvent, dichloromethane, 0.2 mmol of 2-methoxy-5-benzoylazobenzene and 0.1 mL of water were added into a 10 mL quartz test tube equipped with a stirring bar in sequence, and the mixture was mixed to obtain a mixture. The test tube was sealed and placed under sunlight for stirring and reaction for 30 minutes. The illumination was stopped to obtain a reaction mixture. The reaction mixture was extracted with DCM and washed with sodium hydroxide solution for 3 times. The obtained organic phases were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure and recrystallized to obtain the product 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole. The yield of 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole was 99%, and the yield of the column chromatography method was 99%.

[0096] The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum characterization results of the product 7-methoxy-3-(4-cyanophenyl)-2-phenyl-2H-indazole prepared in Example 9 are as follows: 1 H-NMR (CDCl3, 400MHz δ (ppm) 7.66 (d, J = 7.8Hz, 2H), 7.43 (d, J = 24.0Hz, 7H), 7. 26(d,J=7.9Hz,1H),7.13(t,J=7.8Hz,1H),6.66(d,J=7.1Hz,1H),4.05(s,3H); 13 C-NMR (CDCl3, 125MHz) 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 involved in the preparation of 2,3-diphenyl 2H-indazole (only the target product is reflected in the reaction equation) is as follows:

[0099]

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

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

[0102] 20 mmol were prepared using Example 1 and Comparative Example 1. Comparative analysis of time cost and economic cost:

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

[0104] The time for extraction and recrystallization separation and purification of the product adopted by the non-column chromatography method of Example 1 is about 0.5 hours, and the DCM solvent used is less than 20 mL and a small amount of sodium hydroxide solution. The comprehensive material cost is less than RMB 10. Compared with the column chromatography separation and purification method of Comparative Example 1, Example 1 of the present invention saves more than 90% of the cost of separation and purification materials, avoids the use of harmful silica gel powder, and saves 75% of separation and purification time.

[0105] In the process of extracting and recrystallizing the products in other embodiments of the present invention, the time cost and economic cost are similar to those in Embodiment 1, which are significantly better than the time cost and economic cost required for separating and purifying the products by column chromatography.

Claims

1. A non-column chromatography method for preparing 2H-indazole compounds from azobenzene compounds, characterized in that: The following steps are involved: The azobenzene compound, biboric acid ester, water and an organic solvent are mixed, reacted, the organic solvent is removed, extracted, and recrystallized to separate and obtain the 2H-indazole compound; The reaction is carried out under sunlight; The reaction time is less than 1 hour.

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

3. The non-column chromatography method according to claim 1, characterized in that The extraction is performed using at least one of tetrahydrofuran, acetonitrile, methanol or dichloromethane (DCM).

4. The non-column chromatography method according to claim 1, characterized in that After the extraction, the mixture is washed with alkaline solution.

5. The non-column chromatography method according to claim 4, characterized in that After the alkali solution washing is completed, the product is dried, concentrated under reduced pressure, and recrystallized.

6. The non-column chromatography method according to claim 1, characterized in that: The general structural formula of the azobenzene compound is Ar 1 -N=N-Ar 2 , among which Ar 1 and Ar 2 Each independently represents an aryl group or a substituted aryl group; the aryl group is an aromatic ring of 6 to 16 carbon atoms; the substitution refers to substitution by at least one of an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a halogen group, a nitro group, an alkoxy group, an ester group, a sulfonamide group, a cyano group, a carbonyl group, and a trifluoromethyl group.

7. The non-column chromatography method according to claim 1, characterized in that The azobenzene compound is selected from any one of the following:

8. The non-column chromatography method according to claim 1, characterized in that: The 2H-indazole compound is selected from any one of the following:

9. The non-column chromatography method according to claim 1, characterized in that: The biboric acid ester is selected from bis(bis(diphenyl)benzene) borate; and / or, the molar ratio of the azobenzene compound, biboric acid ester and water is 1:(0.5-4.8):(10-100); and / or, the amount ratio of the azobenzene compound to the organic solvent is 0.1mmol:0.5-4.5mL; and / or, the solvent is removed by rotary evaporation.

10. Application of the non-column chromatography method according to any one of claims 1 to 9 in the field of organic synthesis.

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