A green synthesis method of nitrobenzene compounds

Abstract

A green synthesis method of nitrobenzene compounds, in an organic solvent, using aromatic amine as raw material, using an oxidant and a catalyst to form a reaction system, selectively oxidizing aromatic amine into corresponding nitrobenzene compounds, the method selects an oxidant which is green, pollution-free, the catalyst is common, easy to obtain, low in price, and has significant catalytic effect, and the reaction conditions are mild, simple in operation, low in cost, fast in speed, high in selectivity and high in product yield, which is a novel, good scientific research value and industrialization potential synthesis method of nitrobenzene compounds.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of synthesis of organic chemical raw materials and intermediates, and particularly relates to a method for selectively catalyzing oxidation of aromatic amines into corresponding nitrobenzene compounds. BACKGROUND

[0002] Nitro compounds play an important role in organic chemistry. Due to the ease of obtaining and the potential of converting into various functional groups, nitro derivatives are widely used in organic synthesis. Nitroarenes are used as universal building blocks for the synthesis of related chemicals, including drugs, dyes, materials and fragrances. There are many drugs containing nitro groups on the market, such as nitroxoline, furacilin, furantoin, chloramphenicol, etc. Traditional nitration method requires very harsh conditions for large-scale preparation of nitro compounds, poor functional group tolerance, low selectivity, and is not a good preparation method. Direct oxidation of aromatic amines into nitro compounds is safer than traditional nitration method, and therefore is more concerned by people.

[0003] Commonly used oxidants in the oxidation process of aromatic amines include H2O2, m-CPBA, peroxyacetic acid, peroxyfluoroacetic acid, TBHP-KI, TBHP and CrS-2, TBHP and Rh2(cap)4, sodium perborate-tungsten phosphoric acid, H2O2 and CaWO4, etc. Emmons et al. (J. Am. Chem. Soc. 1957, 79, 5528-5530) reported that peroxoacetic acid anhydrous solution synthesized by acetic acid and hydrogen peroxide oxidized aromatic amines to synthesize nitro derivatives under the catalysis of sulfuric acid. This reaction is suitable for the oxidation of anilines with different substituents, and the yield of the target product is high. Ke et al. (Chem. Cat. Chem. 2017, 9, 733-737) reported a method for oxidizing aromatic amines using hierarchical micro-mesoporous-macroporous CuAlPO-5 as catalyst. This method uses TBHP as oxidant, and uses calcined CuAlPO-5 zeolite to selectively oxidize complex aromatic amines into corresponding nitroarenes. At the same time, the CuAlPO-5 catalyst can be efficiently recovered and reused, and has excellent conversion rate and selectivity.

[0004] Dewkar et al. (Angew. Chem. Int. Ed. 2001, 40, 405-408) used H2O2 as oxidant and a new titanium hydrate matrix as heterogeneous catalyst to oxidize primary amines. During the reaction, aliphatic primary amines with α-CH bond are selectively converted into oximes with partially hydrolyzed ketones, and anilines are converted into nitroarenes. This method is suitable for both electron-deficient anilines and electron-rich anilines, and the corresponding nitro compounds have high selectivity.

[0005] Chinese patent CN101602673B discloses a method for preparing nitrobenzene in ionic liquid: in ionic liquid 1-butyl-3-methyl imidazole tetrafluoroborate, using 30% mass concentration H2O2 as oxidant, ammonium molybdate as catalyst, aniline is oxidized to prepare nitrobenzene, the method uses ionic liquid instead of organic solvent, plays the role of solvent and cocatalyst, reduces the harm to human body and environmental pollution.

[0006] At present, there are many methods for selectively synthesizing nitrobenzene compounds, but these methods still need to be improved, for example, some methods have limitations for the oxidation of diamines and polyamines, and the synthesis process requires high equipment and conditions; the reaction system uses expensive oxidants or complex and easy-to-lose catalysts, the cost is large, harmful to the environment, the yield is low, and some catalysts are difficult to recover, and have large application limitations. Therefore, it is of great significance to develop a green, efficient, safe, mild and environmentally friendly approach to synthesize high-value nitrobenzene products. SUMMARY

[0007] The purpose of the present application is to overcome the shortcomings of the prior art and provide a novel method for preparing nitrobenzene compounds by catalytic oxidation of aromatic amines.

[0008] The present application adopts the following technical solutions:

[0009] A green synthesis method of nitrobenzene compounds, in an organic solvent, using aromatic amines as raw materials, using an oxidant and a catalyst to form a reaction system, selectively oxidizing aromatic amines to corresponding nitrobenzene compounds;

[0010] Among them, the catalyst is one or more of tBuOK, NaOEt, NaOMe, NaOH and K3PO4.

[0011] Further, the molar amount of the catalyst is 0.1-2 equiv of the aromatic amine.

[0012] Further, R and R' are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, ester group, alkyl, alkoxy and aryl.

[0013] Further, the organic solvent is one or more of MeCN, DMF, DMSO, DCE, EtOH, H2O, Toluene, tert-Butanol, 1,4-Dioxane, 1-Propanol and CF3CH2OH.

[0014] Further, the organic solvent is a mixed solvent composed of EtOH / MeCN.

[0015] Further, the molar amount of the oxidizing agent is 3-20 equiv of the aromatic amine.

[0016] Further, the room temperature of the oxidation reaction is rt-100℃.

[0017] Further, the time of the oxidation reaction is 10 min-12 h.

[0018] Further, the mass concentration of the hydrogen peroxide is ≥30%.

[0019] Further, the catalyst is NaOMe.

[0020] From the above description of the present application, compared with the prior art, the beneficial effects of the present application are:

[0021] First, the present application uses aromatic amine as raw material, hydrogen peroxide as oxidizing agent, and realizes efficient and selective oxidation of aromatic amine to corresponding nitrobenzene compounds under mild conditions through the selection of catalyst and solvent. The selected oxidizing agent is green, pollution-free, the catalyst is common, easy to obtain, low in price, and has significant catalytic effect, and the reaction conditions are mild, simple in operation, low in cost, fast in rate, high in selectivity and high in product yield. It is a novel synthesis method of nitrobenzene compounds with good scientific research value and industrialization potential.

[0022] Second, sodium methoxide is used as catalyst, which is low in cost, high in activity, good in selectivity, small in environmental pollution, and meets the green environmental protection concept. At the same time, the catalyst has low dosage, and there is no need to consider catalyst recovery and treatment, which greatly simplifies the operation steps.

[0023] Third, the oxidizing agent used in the present application is hydrogen peroxide, and the only by-product after reaction is water, which is pollution-free and has low requirements on reaction equipment and conditions. Compared with traditional oxidizing agents, the cost is greatly reduced, and the safety is improved.

[0024] Fourth, the mixed solvent of ethanol and acetonitrile is used in the present application, which has excellent performance and helps to obtain high yield of target product. The whole catalytic system has strong universality, good scientific research value and great industrialization application potential. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 It is a synthesis route map of nitrobenzene compounds.

[0026] Figure 2 It is a synthesis route map of Example 1.

[0027] Figure 3 It is a synthesis route map of Example 3.

[0028] Figure 4 It is a synthesis route map of Example 4.

[0029] Figure 5 synthetic route map for Example 5;

[0030] Figure 6 synthetic route map for Example 6;

[0031] Figure 7 synthetic route map for Example 7;

[0032] Figure 8 synthetic route map for Example 8;

[0033] Figure 9 synthetic route map for Example 9;

[0034] Figure 10 synthetic route map for Example 10;

[0035] Figure 11 synthetic route map for Example 11;

[0036] Figure 12 synthetic route map for Example 12;

[0037] Figure 13 synthetic route map for Example 13;

[0038] Figure 14 synthetic route map for Example 14;

[0039] Figure 15 synthetic route map for Example 15;

[0040] Figure 16 synthetic route map for Example 16;

[0041] Figure 17 synthetic route map for Example 17;

[0042] Figure 18 synthetic route map for Example 18;

[0043] Figure 19 synthetic route map for Example 19;

[0044] Figure 20 synthetic route map for Example 20;

[0045] Figure 21 synthetic route map for Example 21;

[0046] Figure 22 synthetic route map for Example 22;

[0047] Figure 23 synthetic route map for Example 23;

[0048] Figure 24 Synthetic route for Example 24;

[0049] Figure 25 NMR spectrum of Example 2;

[0050] Figure 26 NMR spectrum of Example 4. DETAILED DESCRIPTION

[0051] The application is further described below through specific embodiments.

[0052] A green synthesis method of nitrobenzene compounds, in an organic solvent, using aromatic amine as raw material, using an oxidant and a catalyst to form a reaction system, selectively oxidizing aromatic amine into corresponding nitrobenzene compounds, the synthesis route is specifically referred to Figure 1 .

[0053] Among them, R, R' are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, ester group, alkyl, alkoxy, aryl.

[0054] The catalyst is one or several of tBuOK, NaOEt, NaOMe, NaOH, K3PO4, and the molar amount of the catalyst is 0.1-2 equiv of the aromatic amine.

[0055] The organic solvent is one or several of MeCN, DMF, DMSO, DCE, EtOH, H2O, Toluene, tert-Butanol, 1,4-Dioxane, 1-Propanol, CF3CH2OH; specifically, the organic solvent is a mixed solvent composed of EtOH / MeCN.

[0056] The mass concentration of hydrogen peroxide is ≥30%; and the molar amount of the oxidant is 3-20 equiv of the aromatic amine.

[0057] The room temperature of the oxidation reaction is rt-100℃, and the time of the oxidation reaction is 10min-12h.

[0058] Example 1

[0059] The synthesis route is specifically referred to Figure 2 .

[0060] Dissolve aniline (2mmol, 186mg) in 4mL acetonitrile, add sodium methoxide (0.2eq, 22mg), add 30% hydrogen peroxide 2mL, react at room temperature for 1h. GC monitoring target product yield is 69.4%.

[0061] The comparative example is set for example 1 to investigate the influence of the amount of catalyst on the reaction. Except for the amount of catalyst, the other conditions are the same as those in example 1. The results of the catalytic oxidation of aniline are shown in Table 1.

[0062] Table 1

[0063]

[0064] As can be seen from Table 1, when the amount of NaOMe added is 0.4 eq of the raw material, the yield of the target product can reach more than 90%, and the yield of the product decreases with the increase of the amount of catalyst. Therefore, the system selects to add 0.4 eq of catalyst.

[0065] Example 2

[0066] Aniline (2 mmol, 186 mg) was dissolved in 4 mL of MeCN, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was carried out at room temperature for 4 h. GC monitoring showed that the yield of the target product was 92.4%. After the reaction was completed, the reaction liquid was poured into 10 mL of water, extracted with dichloromethane three times, and the organic phase was concentrated and separated and purified by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain 110 mg of the target product with a yield of 90%.

[0067] The structure data was confirmed by nuclear magnetic resonance as:

[0068] 1H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 7.5 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.56-7.49 (m, 2H).

[0069] Comparative examples 11-21 are set for example 2 to investigate the influence of different solvents on the reaction. The amount of mixed solvent added in comparative examples 11-18 is Slovent / MeCN=4 mL / 1 mL, and the amount of solvent added in comparative examples 19-21 is 4 mL. The other conditions are the same as those in example 2. The results of the catalytic oxidation of aniline are shown in Table 2.

[0070] Table 2

[0071]

[0072] As can be seen from the above table, when mixed solvents EtOH / MeCN are used, the yield of the target product can reach 96%, which is better than the yield when only MeCN is used as the solvent. Therefore, the system selects to add mixed solvents EtOH / MeCN.

[0073] Example 3

[0074] The synthesis route is referred to Figure 3 .

[0075] Amplification reaction: 3-chloro-2-methyl aniline (35.3 mmol, 5 g) was dissolved in 15 mL of acetonitrile, 20 mL of EtOH was added, sodium methoxide (0.4 eq, 763 mg) was added, and hydrogen peroxide (10 eq, 35 mL) was slowly added dropwise. The reaction was carried out at room temperature for 4 h. GC monitoring showed that the yield of the target product was 96%. That is, this reaction system has strong universality and can be used for large-scale industrial production.

[0076] Example 4

[0077] The synthetic route thereof is referred to Figure 4 .

[0078] P-methylaniline (2 mmol, 214 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the reaction solution was poured into 10 mL of water, extracted with dichloromethane three times, and concentrated. The organic phase was separated and purified by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain 123 mg of the target product with a yield of 90%.

[0079] The structure data was confirmed by nuclear magnetic resonance as:

[0080] 1H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 2.46 (s, 3H).

[0081] Example 5

[0082] The synthetic route thereof is referred to Figure 5 .

[0083] P-methylaniline (2 mmol, 214 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the reaction solution was poured into 10 mL of water, extracted with dichloromethane three times, and concentrated. The organic phase was separated and purified by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain 123 mg of the target product with a yield of 90%.

[0084] The structure data was confirmed by nuclear magnetic resonance as:

[0085] 1H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 2.46 (s, 3H).

[0086] Example 6

[0087] The synthetic route thereof is referred to Figure 6 .

[0088] To 4-tert-butylaniline (2 mmol, 298 mg) in 4 mL acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, and 2 mL of hydrogen peroxide was added, and the reaction was allowed to proceed at room temperature for 4 h. After the reaction was completed, the reaction solution was poured into 10 mL of water, and extracted with dichloromethane three times. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 165 mg with a yield of 92%.

[0089] The structure data was confirmed by nuclear magnetic resonance as:

[0090] 1H NMR (400 MHz, Chloroform-d) δ 8.16 - 8.10 (m, 2H), 7.55 - 7.49 (m, 2H), 1.35 (s, 9H).

[0091] Example 7

[0092] The synthetic route thereof is referred to Figure 7 .

[0093] To 2-ethylaniline (2 mmol, 242 mg) in 4 mL acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, and 2 mL of hydrogen peroxide was added, and the reaction was allowed to proceed at room temperature for 4 h. After the reaction was completed, the reaction solution was concentrated, and the product was precipitated, washed with water three times, and filtered, and the solid was dried to obtain the target product 142 mg with a yield of 94%.

[0094] The structure data was confirmed by nuclear magnetic resonance as:

[0095] 1H NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 8.5 Hz, 1H), 7.50 (td, J = 7.5, 1.4 Hz, 1H), 7.34 (dq, J = 7.0, 4.4, 3.6 Hz, 2H), 2.60 (s, 3H).

[0096] Example 8

[0097] The synthetic route thereof is referred to Figure 8 .

[0098] To 2-ethylaniline (2 mmol, 242 mg) in 4 mL acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, and 2 mL of hydrogen peroxide was added, and the reaction was allowed to proceed at room temperature for 4 h. After the reaction was completed, the reaction solution was concentrated, and the product was precipitated, washed with water three times, and filtered, and the solid was dried to obtain the target product 142 mg with a yield of 94%.

[0099] The structure data was confirmed by nuclear magnetic resonance as:

[0100] 1H NMR (400 MHz, Chloroform-d) δ 7.85 (dd, J = 8.1, 1.4 Hz, 1H), 7.51 (td, J = 7.5, 1.3 Hz, 1H), 7.38 - 7.29 (m, 2H), 2.90 (q, J = 7.5 Hz, 2H), 1.28 (t, J = 7.5 Hz, 3H).

[0101] Example 9

[0102] The synthetic route thereof refers to Figure 9 .

[0103] Dissolve 2,5-dimethylaniline (2 mmol, 242 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add hydrogen peroxide 2 mL, react at room temperature for 10 h. After the reaction is completed, pour the reaction liquid into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and separate and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 127 mg with a yield of 84%.

[0104] The structure data is confirmed by nuclear magnetic resonance as:

[0105] 1H NMR (400 MHz, Chloroform-d) δ 7.76 (s, 1H), 7.29 (d, J = 7.7 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 2.53 (s, 3H), 2.38 (s, 3H).

[0106] Example 10

[0107] The synthetic route thereof refers to Figure 10 .

[0108] Dissolve m-toluidine (2 mmol, 214 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add hydrogen peroxide 2 mL, react at room temperature for 4 h. After the reaction is completed, pour the reaction liquid into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and separate and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 116 mg with a yield of 85%.

[0109] The structure data is confirmed by nuclear magnetic resonance as:

[0110] 1H NMR (400 MHz, Chloroform-d) δ 8.01 (d, J = 11.0 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 2.45 (s, 3H).

[0111] Example 11

[0112] The synthetic route thereof refers to Figure 11 .

[0113] Dissolve 3,5-dimethylaniline (2 mmol, 242 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add hydrogen peroxide 2 mL, react at room temperature for 4 h. After the reaction is completed, the reaction solution is concentrated, the product is precipitated, washed with water three times, filtered, and the solid is dried to obtain the target product 145 mg with a yield of 96%.

[0114] The structure data is confirmed by nuclear magnetic resonance as:

[0115] 1H NMR (400 MHz, Chloroform-d) δ 7.83 (s, 2H), 7.30 (s, 1H), 2.41 (s, 6H).

[0116] Example 12

[0117] The synthetic route thereof refers to Figure 12 .

[0118] Dissolve 4-fluoroaniline (2 mmol, 222 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add hydrogen peroxide 2 mL, react at room temperature for 4 h. After the reaction is completed, pour the reaction solution into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 99 mg with a yield of 70%.

[0119] The structure data is confirmed by nuclear magnetic resonance as:

[0120] 1H NMR (400 MHz, Chloroform-d) δ 8.26 (ddd, J = 8.9, 4.4, 1.8 Hz, 2H), 7.21 (dd, J = 9.2, 7.8 Hz, 2H).

[0121] Example 13

[0122] The synthetic route thereof refers to Figure 13 .

[0123] Dissolve 4-fluoroaniline (2 mmol, 222 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add hydrogen peroxide 2 mL, react at room temperature for 4 h. After the reaction is completed, pour the reaction solution into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 99 mg with a yield of 70%.

[0124] The structure was confirmed by NMR as follows:

[0125] 1H NMR (400 MHz, Chloroform-d) δ 8.22 - 8.15 (m, 2H), 7.55 - 7.49 (m, 2H).

[0126] Example 14

[0127] The synthetic route thereof refers to Figure 14 .

[0128] The p-bromoaniline (2 mmol, 344 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was carried out at room temperature for 4 h. After the reaction was completed, the reaction liquid was poured into 10 mL of water, extracted with dichloromethane three times, the organic phase was concentrated, and then purified by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain the target product 182 mg with a yield of 90%.

[0129] The structure was confirmed by NMR as follows:

[0130] 1H NMR (400 MHz, Chloroform-d) δ 8.13 - 8.07 (m, 2H), 7.72 - 7.66 (m, 2H).

[0131] Example 15

[0132] The synthetic route thereof refers to Figure 15 .

[0133] The p-trifluoromethoxyaniline (2 mmol, 354 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was carried out at 80°C for 12 h. After the reaction was completed, the reaction liquid was concentrated, the product was precipitated, washed with water three times, filtered, and the solid was dried to obtain the target product 182 mg with a yield of 88%.

[0134] The structure was confirmed by NMR as follows:

[0135] 1H NMR (400 MHz, Chloroform-d) δ 8.35 - 8.28 (m, 2H), 7.37 (dd, J = 9.3, 1.1 Hz, 2H).

[0136] Example 16

[0137] The synthetic route thereof refers to Figure 16 .

[0138] Synthesis route of the compound is as follows:

[0139] The structure data was confirmed by nuclear magnetic resonance as follows:

[0140] 1H NMR (400 MHz, Chloroform-d) δ 8.09-8.02 (m, 1H), 7.69-7.61 (m, 1H), 7.34-7.26 (m, 2H).

[0141] Example 17

[0142] Synthesis route of the compound is as follows: Figure 17 .

[0143] Synthesis route of the compound is as follows:

[0144] The structure data was confirmed by nuclear magnetic resonance as follows:

[0145] 1H NMR (400 MHz, Chloroform-d) δ 8.52 (s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.77-7.71 (m, 1H).

[0146] Example 18

[0147] Synthesis route of the compound is as follows: Figure 18 .

[0148] Synthesis route of the compound is as follows:

[0149] The structure was confirmed by NMR as follows:

[0150] 1H NMR (400 MHz, Chloroform-d) δ 7.38 (d, J = 3.1 Hz, 1H), 7.10 (dd, J = 9.2, 3.1 Hz, 1H), 7.02 (d, J = 9.2 Hz, 1H), 3.91 (s, 3H), 3.81 (s, 3H).

[0151] Example 19

[0152] The synthetic route thereof refers to Figure 19 .

[0153] 2-chloro-5-methylaniline (2 mmol, 282 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was carried out at room temperature for 4 h. After the reaction was completed, the reaction solution was poured into 10 mL of water, extracted with dichloromethane three times, the organic phase was concentrated, and column chromatography separation and purification (gradient of 0-5% PE:EA) was carried out on silica gel to obtain 123 mg of the target product with a yield of 72%.

[0154] The structure was confirmed by NMR as follows:

[0155] 1H NMR (400 MHz, Chloroform-d) δ 7.66 (s, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.31 (dd, J = 8.4, 2.1 Hz, 1H), 2.40 (s, 3H).

[0156] Example 20

[0157] The synthetic route thereof refers to Figure 20 .

[0158] 3-chloro-4-methylaniline (2 mmol, 282 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was carried out at room temperature for 4 h. After the reaction was completed, the reaction solution was poured into 10 mL of water, extracted with dichloromethane three times, the organic phase was concentrated, and column chromatography separation and purification (gradient of 0-5% PE:EA) was carried out on silica gel to obtain 153 mg of the target product with a yield of 89%.

[0159] The structure was confirmed by NMR as follows:

[0160] 1H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 2.3 Hz, 1H), 8.01 (dd, J = 8.4, 2.3 Hz, 1H), 7.40 (d, J = 9.2 Hz, 1H), 2.47 (s, 3H).

[0161] Example 21

[0162] The synthetic route thereof refers to Figure 21 .

[0163] Dissolve 3,4-dichloroaniline (2 mmol, 324 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add 2 mL of hydrogen peroxide, and react at room temperature for 12 h. After the reaction is completed, pour the reaction solution into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain 136 mg of the target product with a yield of 71%.

[0164] The structure data is confirmed by nuclear magnetic resonance as:

[0165] 1H NMR (400 MHz, Chloroform-d) δ 7.66 (s, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.31 (dd, J = 8.2, 2.1 Hz, 1H), 2.40 (s, 3H).

[0166] Example 22

[0167] The synthetic route thereof refers to Figure 22 .

[0168] Dissolve o-phenylenediamine (2 mmol, 216 mg) in 4 mL of acetonitrile, add sodium methoxide (0.4 eq, 44 mg), add 2 mL of hydrogen peroxide, and react at room temperature for 12 h. After the reaction is completed, pour the reaction solution into 10 mL of water, extract with dichloromethane three times, concentrate the organic phase, and purify by silica gel column chromatography (gradient of 0-5% PE:EA) to obtain 104 mg of the target product with a yield of 75%.

[0169] The structure data is confirmed by nuclear magnetic resonance as:

[0170] 1H NMR (400 MHz, Chloroform-d) δ 8.11 (dt, J = 8.6, 1.4 Hz, 1H), 7.36 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 6.81 (dd, J = 8.4, 1.3 Hz, 1H), 6.70 (ddt, J = 8.2, 7.0, 1.2 Hz, 1H), 6.06 (s, 2H).

[0171] Example 23

[0172] The synthetic route thereof refers to Figure 23 .

[0173] The 4,5-dichloro-1,2-phenylenediamine (2 mmol, 354 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was allowed to proceed at room temperature for 12 h. After the reaction was completed, the reaction solution was concentrated, the product was precipitated, washed with water three times, filtered, and the solid was dried to obtain the target product 192 mg with a yield of 93%.

[0174] The structure data was confirmed by nuclear magnetic resonance as follows:

[0175] 1H NMR (400 MHz, Chloroform-d) δ 8.24 (s, 1H), 6.97 (s, 1H), 6.10 (s, 2H).

[0176] Example 24

[0177] The synthesis route thereof is shown in Figure 24 .

[0178] The 4,5-dichloro-1,2-phenylenediamine (2 mmol, 354 mg) was dissolved in 4 mL of acetonitrile, sodium methoxide (0.4 eq, 44 mg) was added, 2 mL of hydrogen peroxide was added, and the reaction was allowed to proceed at room temperature for 12 h. After the reaction was completed, the reaction solution was concentrated, the product was precipitated, washed with water three times, filtered, and the solid was dried to obtain the target product 192 mg with a yield of 93%.

[0179] The structure data was confirmed by nuclear magnetic resonance as follows:

[0180] 1H NMR (400 MHz, DMSO-d6) δ 8.30 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H), 7.73 (s, 0H).

[0181] In summary, the present application uses aromatic amine as raw material, hydrogen peroxide as oxidant, and realizes the efficient and selective oxidation of aromatic amine to the corresponding nitrobenzene compound under mild conditions through the screening of catalysts and solvents; the selected oxidant is green, pollution-free, the catalyst is common, easy to obtain, low in price, and has significant catalytic effect, and the reaction conditions are mild, simple in operation, low in cost, fast in rate, high in selectivity, and high in product yield, so that the present application is a novel synthesis method of nitrobenzene compound with good scientific research value and industrialization potential.

[0182] The above merely describes preferred embodiments of the present application, and therefore cannot limit the scope of the present application, i.e., equivalent changes and modifications made according to the patent application scope and content of the present application should still fall within the scope of the present application.

Claims

1. A green synthesis method of nitrobenzene compounds, characterized by: In an organic solvent, aromatic amine is used as raw material, and a reaction system composed of an oxidant and a catalyst is used to selectively oxidize the aromatic amine into a corresponding nitrobenzene compound, and the synthesis route is specifically as follows: ； The oxidant is hydrogen peroxide; The molar amount of the catalyst is 0.4 equiv of the aromatic amine; R and R' are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, ester group, alkyl, alkoxy, aryl; The organic solvent is a mixed solvent composed of EtOH / MeCN; The molar amount of the oxidant is 3-20 equiv of the aromatic amine; The catalyst is NaOMe; The reaction temperature is room temperature.

2. A green synthesis of nitrobenzene compounds as claimed in claim 1, wherein: The reaction time is 10 min-12 h.

3. A green synthesis of nitrobenzene compounds as claimed in claim 1, wherein: The mass concentration of the hydrogen peroxide is ≥30%.

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