A green synthesis method of azoxybenzene compounds

Abstract

A green synthesis method of azoxybenzene compounds, in an organic solvent, using aromatic amine or aromatic heteroamine as raw material, using an oxidant and a catalyst to form a reaction system, selectively oxidizing the aromatic amine into the corresponding azoxy compound; wherein the catalyst is one or several of NaOAc, sodium formate, KF, NaF, CsF, CaF2 and R''4NF, wherein R'' is one of alkyl, methyl, ethyl and butyl; the catalyst used in the application has low cost, high activity, good selectivity and small environmental pollution compared with the metal catalyst of the prior art, and conforms to the green environmental protection concept; at the same time, the catalyst has small dosage, and does not need to consider catalyst recovery treatment and other problems, greatly simplifying the operation steps.

Description

Technical Field

[0001] This invention belongs to the field of synthesis of organic chemical raw materials and intermediates, and specifically relates to a green synthesis method for selectively catalytically oxidizing aromatic amines or aromatic heteroamines to the corresponding azobenzene compounds. Background Technology

[0002] Azobenzene oxides possess unique 1,3-dipolar ON=N bonds and are widely used in pharmaceuticals, dyes, resins, food additives, and liquid crystal materials, showing a promising market prospect. Currently, azobenzene oxides are selectively prepared mainly through two pathways: oxidation of aromatic amino compounds and reduction of aromatic nitro compounds. For detailed synthetic routes, please refer to [link to relevant documentation]. Figure 1 However, both processes require stringent reaction conditions and have poor selectivity for the target product, making them challenging.

[0003] Common reducing agents used in the reduction of aromatic nitro compounds include borohydrides, hydrazine hydrate, alcohols, and CO. For example, Yufang Liu et al. (Molecules 2011, 16, 3563-3568) used potassium borohydride in water to reduce several nitro aromatics to the corresponding azobenzene oxides under the condition of PEG-400 as a phase transfer catalyst. This method has simple experimental steps and high reaction efficiency. Ruiping Wei et al. (Synth. Commun. 2019, 49:5, 688-696) developed a catalyst-free system for the reduction of nitrobenzene to multiple products. Using nitrobenzene as a raw material and an alcohol as a reducing agent, KOH was used to promote the selective reduction of nitrobenzene to azobenzene oxides and aniline. This method only requires changing the alcohol and the temperature to complete the selective conversion, and is simple, economical, and practical.

[0004] Hydrogen peroxide is commonly used as an oxidant in the oxidation of aromatic amine compounds, although oxygen or air is sometimes employed. For example, J. Qin et al. (Angew. Chem. Int. Ed. 2022, 61, e202112907) developed a low-cost, multifunctional Zr(OH)4 heterogeneous catalyst for the selective oxidation of aniline to azobenzene oxide in H2O2 or O2 systems. Song Yuwan et al. (Organic Chemistry, 2019, 39(04): 1181-1186) reported a method to improve the efficient and selective conversion of aniline to the corresponding azobenzene oxide by adjusting the silicon-titanium molar ratio of TS-1. When the silicon-titanium molar ratio of TS-1 was 80, aryl aniline was converted to the corresponding azobenzene oxide compounds with good yield and high selectivity using H2O2 as the oxidant.

[0005] Currently, there are many methods for synthesizing azobenzene, but these methods still have room for improvement. For example, the synthesis process requires high-quality equipment and conditions, the reaction system uses precious metals or toxic catalysts, which are harmful to the environment, and some catalysts are difficult to recover, resulting in high costs and limited applications. Therefore, developing a green, efficient, and safe route to obtain high-value-added azobenzene products is of great significance. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide a green synthesis method for azobenzene compounds.

[0007] The present invention adopts the following technical solution:

[0008] A green synthesis method for azobenzene compounds involves using aromatic amines or aromatic heteroamines as raw materials in an organic solvent and utilizing a reaction system composed of an oxidant and a catalyst to selectively oxidize the aromatic amines to the corresponding azo compounds.

[0009] The catalyst is one or more of NaOAc, sodium formate, KF, NaF, CsF, CaF2, and R″4NF, where R″ is an alkyl group, methyl, ethyl, or butyl.

[0010] Furthermore, the molar amount of the catalyst is 0.1-3 equiv of aromatic amine or aromatic heteroamine.

[0011] Furthermore, the catalyst is NaF.

[0012] Furthermore, the molar amount of the oxidant is 3-20 equiv of aromatic amine or aromatic heteroamine.

[0013] Furthermore, the oxidant is hydrogen peroxide.

[0014] Furthermore, the mass concentration of the hydrogen peroxide is ≥30%.

[0015] Furthermore, R and R′ are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, -CN, ester group, alkyl, alkoxy, and aryl; Ar is an aromatic ring or aromatic heterocycle, the aromatic ring is selected from a benzene ring or a naphthyl ring, and the aromatic heterocycle is selected from pyridine, thiophene, furan, pyridazine, pyrimidine, pyrazine, oxazole, isoxazole, thiazole, isothiazole, quinoline, benzothiazole, or isoquinoline.

[0016] Furthermore, the organic solvent is one or more of MeCN, DMF, DMSO, DCE, EtOH, and H2O.

[0017] Furthermore, the reaction temperature is room temperature rt-100℃.

[0018] Furthermore, the reaction time is 1 hour to 36 hours.

[0019] As can be seen from the above description of the present invention, compared with the prior art, the beneficial effects of the present invention are:

[0020] First, this invention uses aromatic amines or aromatic heteroamines as raw materials. Through screening of catalysts and solvents, and using hydrogen peroxide as an oxidant, it achieves efficient and selective oxidation of aromatic amines or aromatic heteroamines to the corresponding azobenzene oxide compounds under mild conditions. The oxidant used in this method is green, environmentally friendly, and pollution-free. The catalyst is common, readily available, inexpensive, and has a significant catalytic effect. Furthermore, the reaction conditions are mild, the operation is simple, the cost is low, the rate is fast, the selectivity is high, and the product yield is high. This is a novel method for synthesizing azobenzene oxide compounds with good scientific research value and industrialization potential.

[0021] Secondly, the catalyst used in this invention is lower in cost, higher in activity, better in selectivity, and less polluting to the environment than traditional metal catalysts, which is in line with the concept of green environmental protection. At the same time, the amount of catalyst used is small, and there is no need to consider issues such as catalyst recycling and treatment, which greatly simplifies the operation steps.

[0022] Third, the solvent acetonitrile used in this invention has excellent performance and simple post-reaction processing, which can quickly obtain the target product with high yield. Moreover, the entire catalytic system has strong universality, good scientific research value and great potential for industrial application.

[0023] Fourth, the oxidant used in this invention is hydrogen peroxide, which produces only water as a byproduct after the reaction, resulting in no pollution. Furthermore, it has low requirements for reaction equipment and conditions, significantly reducing costs and improving safety compared to traditional oxidants.

[0024] Fifth, the aromatic amines or aromatic heteroamines used in this invention are basic industrial raw materials that are inexpensive and readily available. Attached Figure Description

[0025] Figure 1 This is a diagram illustrating the reaction mechanism of the oxidation of aromatic amino compounds and the reduction of aromatic nitro compounds.

[0026] Figure 2 This is a synthetic route diagram for the azobenzene compounds of this invention;

[0027] Figure 3 This is the synthesis route diagram for Example 1;

[0028] Figure 4 This is the synthesis route diagram for Example 4;

[0029] Figure 5 This is the synthesis route diagram for Example 5;

[0030] Figure 6This is the synthesis route diagram for Example 6;

[0031] Figure 7 This is the synthesis route diagram for Example 7;

[0032] Figure 8 This is the synthesis route diagram for Example 8;

[0033] Figure 9 This is the synthesis route diagram for Example 9;

[0034] Figure 10 This is a synthetic route diagram for Example 10;

[0035] Figure 11 This is a synthetic route diagram for Example 11;

[0036] Figure 12 This is the synthesis route diagram for Example 12;

[0037] Figure 13 This is the synthesis route diagram for Example 13;

[0038] Figure 14 This is the synthesis route diagram for Example 14;

[0039] Figure 15 This is the synthesis route diagram for Example 15;

[0040] Figure 16 This is the synthesis route diagram for Example 16;

[0041] Figure 17 This is the synthesis route diagram for Example 17;

[0042] Figure 18 This is the synthesis route diagram for Example 18;

[0043] Figure 19 This is the synthesis route diagram for Example 19;

[0044] Figure 20 This is a synthetic route diagram for Example 20;

[0045] Figure 21 This is a synthetic route diagram for Example 21;

[0046] Figure 22 This is the synthesis route diagram for Example 22;

[0047] Figure 23 This is the synthesis route diagram for Example 23;

[0048] Figure 24 This is a synthetic route diagram for Example 24;

[0049] Figure 25 This is the synthesis route diagram for Example 25;

[0050] Figure 26 This is the synthesis route diagram for Example 26;

[0051] Figure 27 The proton NMR spectrum of Example 1;

[0052] Figure 28 This is the proton NMR spectrum of Example 4. Detailed Implementation

[0053] The present invention will be further described below through specific embodiments.

[0054] A green synthetic method for azobenzene oxides involves using aromatic amines or aromatic heteroamines as raw materials in an organic solvent. A reaction system consisting of an oxidant and a catalyst is used to selectively oxidize the aromatic amines to the corresponding azo compounds. The specific synthetic route is detailed in [link to synthetic route description]. Figure 2 Specifically, the reaction temperature is room temperature to 100℃; the reaction time is 1h to 36h.

[0055] Wherein, R and R′ are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, -CN, ester group, alkyl, alkoxy, and aryl; Ar is an aromatic ring or aromatic heterocycle, the aromatic ring is selected from benzene ring or naphthyl ring, and the aromatic heterocycle is selected from pyridine, thiophene, furan, pyridazine, pyrimidine, pyrazine, oxazole, isoxazole, thiazole, isothiazole, quinoline, benzothiazole, or isoquinoline.

[0056] The catalyst is one or more of NaOAc, sodium formate, KF, NaF, CsF, CaF2, and R″4NF, wherein R″ is an alkyl group, methyl, ethyl, or butyl. Specifically, the molar amount of the catalyst is 0.1-3 equiv of the aromatic amine or aromatic heteroamine.

[0057] The oxidant is hydrogen peroxide, and the mass concentration of hydrogen peroxide is ≥30%; specifically, the molar amount of the oxidant is 3-20 equiv of aromatic amine or aromatic heteroamine.

[0058] The organic solvent is one or more of MeCN, DMF, DMSO, DCE, EtOH, and H2O.

[0059] The present invention will be further described in detail below with reference to specific embodiments, but the content of the present invention is not limited thereto. The processes, conditions, experimental methods, etc., for implementing the present invention, except for those specifically mentioned below, are all common knowledge and general knowledge in the field, and the present invention does not have any particular limitations.

[0060] Example 1

[0061] For its synthetic route, please refer to Figure 3 .

[0062] Aniline (2 mmol, 186 mg) was dissolved in 4 mL of acetonitrile, and sodium fluoride (0.2 eq, 17 mg) was added. Then, 2 mL of 30% hydrogen peroxide was added, and the mixture was reacted at 80 °C for 1 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient 0–5% PE:EA) to obtain a yellow oily substance with a yield of 91%.

[0063] The structural data confirmed by nuclear magnetic resonance are as follows:

[0064] 1H NMR (400MHz, Chloroform-d) δ8.34–8.29(m,2H),8.20–8.15(m,2H),7.60–7.46(m,5H),7.43–7.37(m,1H).

[0065] For Example 1, Comparative Examples 1-6 were set up to investigate the effects of catalyst dosage and reaction time on the reaction. Except for catalyst dosage and reaction time, the other conditions were the same as in Example 1. The catalytic results of aniline are shown in Table 1.

[0066] Table 1

[0067]

[0068] As shown in Table 1, when the amount of NaF added is 0.2 eq of the raw material, the yield of the target product can reach more than 90%. Moreover, the product yield increases and the reaction time decreases with the increase of catalyst amount. Therefore, 2 eq of catalyst is selected for this system.

[0069] Example 2

[0070] Aniline (2 mmol, 186 mg) was dissolved in 4 mL of DMF, sodium fluoride (2 eq, 168 mg) was added, followed by 2 mL of hydrogen peroxide. The mixture was reacted at 80 °C for 1 h. GC monitoring showed that the yield of the target product was 92%.

[0071] For Example 2, Comparative Examples 7-15 were set up to investigate the effect of different catalysts on the reaction. The amount of catalyst used was 4 mmol, and the other conditions were the same as in Example 2. The catalytic oxidation results of aniline are shown in Table 2.

[0072] Table 2

[0073]

[0074] Example 3

[0075] Scale-up reaction: Aniline (53.7 mmol, 5 g) was dissolved in 20 mL of acetonitrile, sodium fluoride (1 eq, 2.25 g) was added, and hydrogen peroxide (5 eq, 27 mL) was slowly added dropwise to the above reaction solution. The reaction was carried out at 80 °C for 4 h; GC monitoring showed that the yield of the target product was 96%. That is, the reaction system has strong universality and can be used for large-scale industrial production.

[0076] Example 4

[0077] See the synthesis route. Figure 4 .

[0078] p-Fluoroaniline (2 mmol, 222 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 2 h. After the reaction was completed, the reaction solution was concentrated, and the product precipitated out. After washing three times with water, the product was filtered, and the solid was dried to obtain 210 mg of yellow powder, with a yield of 96%.

[0079] The structural data confirmed by nuclear magnetic resonance are as follows:

[0080] 1H NMR(400MHz,Chloroform-d)δ8.35–8.29(m,2H),8.29–8.23(m,2H),7.22–7.13(m,4H).19F NMR (376MHz, Chloroform-d) δ -108.03 (q, J = 6.3Hz), -108.59 (q, J = 6.9Hz).

[0081] Example 5

[0082] See the synthesis route. Figure 5 .

[0083] p-Chloroaniline (2 mmol, 254 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 2 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 260 mg of a yellow solid, with a yield of 98%.

[0084] The structural data confirmed by nuclear magnetic resonance are as follows:

[0085] 1H NMR (400MHz, Chloroform-d) δ8.28–8.23(m,2H),8.19–8.13(m,2H),7.51–7.42(m,4H).

[0086] Example 6

[0087] See the synthesis route. Figure 6 .

[0088] p-Methoxyaniline (2 mmol, 246 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 2 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 253 mg of yellow solid, with a yield of 98%.

[0089] The structural data confirmed by nuclear magnetic resonance are as follows:

[0090] 1 H NMR (400MHz, Chloroform-d) δ8.31–8.18(m,4H),7.00–6.93(m,4H),3.92–3.86(m,6H).

[0091] Example 7

[0092] See the synthesis route. Figure 7 .

[0093] p-tert-butylaniline (2 mmol, 298 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 2 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 285 mg of yellow crystals, with a yield of 92%.

[0094] The structural data confirmed by nuclear magnetic resonance are as follows:

[0095] 1 H NMR (400MHz, Chloroform-d) δ 8.23–8.18 (m, 2H), 8.17–8.12 (m, 2H), 7.53–7.48 (m, 4H), 1.37 (d, J = 2.9Hz, 18H).

[0096] Example 8

[0097] See the synthesis route. Figure 8 .

[0098] p-Trifluoromethoxyaniline (2 mmol, 354 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 3 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 348 mg of white crystals, with a yield of 95%.

[0099] The structural data confirmed by nuclear magnetic resonance are as follows:

[0100] 1H NMR (400MHz, Chloroform-d) δ 8.40–8.34 (m, 2H), 8.28–8.22 (m, 2H), 7.34 (dd, J = 12.5, 8.7Hz, 4H). 19F NMR (376MHz, Chloroform-d) δ - 57.69, -57.79.

[0101] Example 9

[0102] See the synthesis route. Figure 9 .

[0103] 4-Alynylaniline (2 mmol, 234 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 2 h. After the reaction was completed, the reaction solution was concentrated, and a solid precipitated out. The solid was washed three times with water, filtered, and dried to obtain a yellow solid with a yield of 96%.

[0104] The structural data confirmed by nuclear magnetic resonance are as follows:

[0105] 1H NMR (400MHz, Chloroform-d) δ8.31–8.24(m,1H),8.18–8.13(m,1H),7.65–7.56(m,2H),3.27(s,1H),3.21(s,0H).

[0106] Example 10

[0107] See the synthesis route. Figure 10 .

[0108] o-Fluoroaniline (2 mmol, 222 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 12 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 166 mg of yellow solid, with a yield of 71%.

[0109] The structural data confirmed by nuclear magnetic resonance are as follows:

[0110] 1H NMR(400MHz,Chloroform-d)δ8.25–8.19(m,1H),7.86(td,J=7.9,1.8Hz,1H),7.44(tdd,J=8.1,4.6,1.7Hz,1H),7.34–7.28(m,1H),7.24–7.12(m,4H).19F NMR (376MHz, Chloroform-d) δ -115.92 (dt, J = 11.9, 6.1Hz), -120.70 (dt, J = 11.4, 5.4Hz).

[0111] Example 11

[0112] See the synthesis route. Figure 11 .

[0113] o-Chloroaniline (2 mmol, 254 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 12 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 215 mg of yellow solid, with a yield of 81%.

[0114] The structural data confirmed by nuclear magnetic resonance are as follows:

[0115] 1H NMR(400MHz,Chloroform-d)δ8.01(dd,J=8.0,1.7Hz,1H),7.76(dd,J=7.5,2.1Hz,1H),7.5 7–7.51(m,2H),7.48–7.42(m,2H),7.39(td,J=7.7,1.4Hz,1H),7.31(td,J=7.7,1.7Hz,1H).

[0116] Example 12

[0117] See the synthesis route. Figure 12 .

[0118] o-Toluidine (2 mmol, 214 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 12 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 199 mg of yellow solid, with a yield of 88%.

[0119] The structural data confirmed by nuclear magnetic resonance are as follows:

[0120] 1H NMR(400MHz,Chloroform-d)δ8.03(dd,J=7.5,2.3Hz,1H),7.68(dd,J=8.1,1.5Hz,1H ),7.42–7.37(m,1H),7.35–7.30(m,4H),7.29–7.27(m,1H),2.53(s,3H),2.38(s,3H).

[0121] Example 13

[0122] See the synthesis route. Figure 13 .

[0123] 2,6-Difluoroaniline (2 mmol, 258 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 12 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 227 mg of yellow solid, with a yield of 84%.

[0124] The structural data confirmed by nuclear magnetic resonance are as follows:

[0125] 1H NMR (400MHz, Chloroform-d) δ7.48(tt,J=8.6,5.9Hz,1H),7.33(tt,J=8.5,6.0Hz,1H),7.12(t,J=8.0Hz,2H),7.04(t,J=8.4Hz,2H).19F NMR (376MHz, Chloroform-d) δ -113.50 (t, J = 7.3Hz), -120.53 (t, J = 7.3Hz).

[0126] Example 14

[0127] See the synthesis route. Figure 14 .

[0128] m-Toluidine (2 mmol, 214 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 12 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 219 mg of a yellow oil, with a yield of 97%.

[0129] The structural data confirmed by nuclear magnetic resonance are as follows:

[0130] 1H NMR(400MHz,Chloroform-d)δ8.24(dd,J=13.3,2.3Hz,1H),8.10–8.04(m,2H),7.9 9 (ddd, J = 9.0, 2.4, 1.5 Hz, 1H), 7.02 (td, J = 8.9, 2.0 Hz, 2H), 3.97 (d, J = 3.9 Hz, 6H).

[0131] Example 15

[0132] See the synthesis route. Figure 15 .

[0133] 2 mmol (322 mg) of m-trifluoromethylaniline was dissolved in 4 mL of acetonitrile, and 4 mmol (168 mg) of sodium fluoride and 2 mL of hydrogen peroxide were added. The mixture was reacted at 80 °C for 1.5 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 311 mg of a yellow-green solid, with a yield of 93%.

[0134] The structural data confirmed by nuclear magnetic resonance are as follows:

[0135] 1H NMR(400MHz,Chloroform-d)δ8.63(s,1H),8.54(d,J=8.3Hz,1H),8.48(s,1H), 8.38(d,J=7.8Hz,1H),7.87(d,J=7.7Hz,1H),7.67(dt,J=24.7,8.1Hz,3H).19F NMR(376MHz,Chloroform-d)δ-62.69,-62.74.

[0136] Example 16

[0137] See the synthesis route. Figure 16 .

[0138] 2,4-Difluoroaniline (2 mmol, 258 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 5 h. After the reaction was completed, the reaction solution was concentrated, washed three times with water, filtered, and the solid was dried to give 248 mg of a yellow solid, with a yield of 92%.

[0139] The structural data confirmed by nuclear magnetic resonance are as follows:

[0140] 1H NMR(400MHz,Chloroform-d)δ8.61–8.52(m,1H),8.02–7.93(m,1H),7.06–6.93(m,4H).19F NMR(376MHz,Chloroform-d)δ-103.46,-105.16,-110.83,-114.45.

[0141] Example 17

[0142] See the synthesis route. Figure 17 .

[0143] 2,5-Difluoroaniline (2 mmol, 258 mg) was dissolved in 4 mL of acetonitrile, and sodium fluoride (4 mmol, 168 mg) and 2 mL of hydrogen peroxide were added. The mixture was reacted at 80 °C for 12 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 251 mg of a yellow solid, with a yield of 93%.

[0144] The structure was confirmed by nuclear magnetic resonance (NMR) as follows: 1H NMR (400MHz, Chloroform-d) δ 8.25–8.18 (m, 1H), 7.72–7.66 (m, 1H), 7.31–7.26 (m, 1H), 7.24 (dd, J = 4.4, 1.9Hz, 1H), 7.19 (td, J = 9.4, 4.8Hz, 1H), 7.15–7.08 (m, 1H).

[0145] Example 18

[0146] See the synthesis route. Figure 18 .

[0147] 3,5-Difluoroaniline (2 mmol, 258 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 13 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 259 mg of yellow solid, with a yield of 96%.

[0148] The structural data confirmed by nuclear magnetic resonance are as follows: 1H NMR (400MHz, Chloroform-d) δ 7.91–7.84 (m, 2H), 7.79–7.72 (m, 2H), 7.07 (tt, J = 8.2, 2.4Hz, 1H), 6.91 (tt, J = 8.5, 2.4Hz, 1H). 19F NMR (376MHz, Chloroform-d) δ -106.55 (t, J = 7.6Hz), -108.67 (t, J = 8.2Hz).

[0149] Example 19

[0150] See the synthesis route. Figure 19 .

[0151] 3,4-Difluoroaniline (2 mmol, 258 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 8 h. After the reaction was completed, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 262 mg of yellow solid, with a yield of 97%.

[0152] The structural data confirmed by nuclear magnetic resonance are as follows:

[0153] 1H NMR(400MHz,Chloroform-d)δ8.33(ddd,J=12.2,7.7,2.4Hz,1H),8.22–8.16(m, 1H),8.14–8.09(m,1H),7.89(ddt,J=8.7,4.3,2.1Hz,1H),7.36–7.23(m,2H).19F NMR (376MHz, Chloroform-d) δ -131.16 (dt, J = 20.7, 10.4Hz), -131.77--131.98 (m), -133.85 (dt, J = 19.5, 9.2Hz), -135.17 (dt, J = 20.9, 10.5Hz).

[0154] Example 20

[0155] See the synthesis route. Figure 20 .

[0156] 3-Methoxy-4-fluoroaniline (2 mmol, 282 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The reaction was carried out at 80 °C for 10 h. After the reaction was completed, the reaction solution was concentrated, and a solid precipitated out. The solid was filtered, washed three times with water, and the filter cake was dried to obtain 288 mg of yellow solid, with a yield of 98%.

[0157] The structural data confirmed by nuclear magnetic resonance are as follows:

[0158] 1H NMR(400MHz,Chloroform-d)δ8.06(dd,J=8.3,2.3Hz,1H),7.95(dd,J=7.6,2.6Hz,1H),7.92–7.88(m,1 H),7.79(ddd,J=8.9,4.4,2.4Hz,1H),7.18(ddd,J=10.7,8.8,3.4Hz,2H),4.00(s,3H),3.96(s,3H).19F NMR (376MHz, Chloroform-d) δ -129.34 (t, J = 10.3Hz), -129.55 (dd, J = 14.3, 8.4Hz).

[0159] Example 21

[0160] See the synthesis route. Figure 21 .

[0161] 3-Chloro-4-fluoroaniline (2 mmol, 290 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 2 h. After the reaction was completed, the reaction solution was concentrated, and a solid precipitated out. The solid was filtered, washed three times with water, and the filter cake was dried to give 296 mg of a white solid, with a yield of 98%.

[0162] The structural data confirmed by nuclear magnetic resonance are as follows:

[0163] 1H NMR (400MHz, Chloroform-d) δ8.47 (dd, J=7.2, 2.4Hz, 1H), 8.42 (dd, J=6.5, 2.7Hz, 1H), 8.23 ​​(ddd, J= 9.0,4.2,2.7Hz,1H),8.08(ddd,J=9.0,4.6,2.4Hz,1H),7.31–7.26(m,1H),7.24(d,J=8.8Hz,1H).19F NMR(376MHz,Chloroform-d)δ-109.32,-110.21.

[0164] Example 22

[0165] See the synthesis route. Figure 22 .

[0166] 2-Fluoro-4-chloroaniline (2 mmol, 290 mg) was dissolved in 4 mL of acetonitrile, and sodium fluoride (4 mmol, 168 mg) and 2 mL of hydrogen peroxide were added. The mixture was reacted at 80 °C for 14 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 260 mg of a yellow solid, with a yield of 86%.

[0167] The structural data confirmed by nuclear magnetic resonance are as follows:

[0168] 1H NMR(400MHz,Chloroform-d)δ8.43(dd,J=9.1,7.9Hz,1H),7.95–7.88(m,1H),7.34–7.26(m,2H),7.25–7.20(m,2H).19F NMR (376MHz, Chloroform-d) δ -112.98 (t, J = 9.0Hz), -116.67 (t, J = 8.9Hz).

[0169] Example 23

[0170] See the synthesis route. Figure 23 .

[0171] 3-Fluoro-4-methoxyaniline (2 mmol, 282 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 12 h. After the reaction was completed, the reaction solution was concentrated, and a solid precipitated out. The solid was filtered, washed three times with water, and the filter cake was dried to give 276 mg of a yellow solid, with a yield of 94%.

[0172] The structural data confirmed by nuclear magnetic resonance are as follows:

[0173] 1H NMR(400MHz,Chloroform-d)δ8.24(dd,J=13.3,2.3Hz,1H),8.11–8.04(m,2H),7.99 (ddt,J=8.9,2.5,1.5Hz,1H),7.02(td,J=8.9,1.6Hz,2H),3.97(d,J=3.8Hz,6H).19F NMR (376MHz, Chloroform-d) δ -132.53 (t, J = 9.8Hz), -133.55 (dd, J = 13.4, 9.1Hz).

[0174] Example 24

[0175] See the synthesis route. Figure 24 .

[0176] 2,5-Dimethylaniline (2 mmol, 242 mg) was dissolved in 4 mL of acetonitrile, and sodium fluoride (4 mmol, 168 mg) and 2 mL of hydrogen peroxide were added. The mixture was reacted at 80 °C for 8 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 199 mg of a yellow solid, with a yield of 88%.

[0177] The structural data confirmed by nuclear magnetic resonance are as follows:

[0178] 1H NMR (400MHz, Chloroform-d) δ7.75(s,1H),7.47(s,1H),7.22–7.17(m,3H),7.07(d,J=9.8Hz,1H),2.47(s,3H),2.39(d,J=5.6Hz,6H),2.31(s,3H).

[0179] Example 25

[0180] See the synthesis route. Figure 25 .

[0181] 3-Chloro-4-methylaniline (2 mmol, 282 mg) was dissolved in 4 mL of acetonitrile, sodium fluoride (4 mmol, 168 mg) was added, and 2 mL of hydrogen peroxide was added. The mixture was reacted at 80 °C for 4 h. After the reaction was completed, the reaction solution was concentrated, and a solid precipitated out. The solid was filtered, washed three times with water, and dried to obtain 282 mg of a yellow solid, with a yield of 96%.

[0182] The structural data confirmed by nuclear magnetic resonance are as follows:

[0183] 1H NMR(400MHz,Chloroform-d)δ8.33–8.29(m,2H),8.09(dd,J=8.3,2.3Hz,1H),7.9 7(dd,J=8.3,2.0Hz,1H),7.35(dd,J=10.5,7.9Hz,2H),2.47(s,3H),2.44(s,3H).

[0184] Example 26

[0185] See the synthesis route. Figure 26 .

[0186] 3-Aminopyridine (2 mmol, 188 mg) was dissolved in 4 mL of acetonitrile, and sodium fluoride (4 mmol, 168 mg) and 2 mL of hydrogen peroxide were added. The mixture was reacted at 80 °C for 12 h. After the reaction was complete, the reaction solution was poured into 10 mL of water and extracted three times with dichloromethane. The organic phase was concentrated and purified by silica gel column chromatography (gradient of 0–5% PE:EA) to obtain 196 mg of a white solid, with a yield of 98%.

[0187] The structural data confirmed by nuclear magnetic resonance are as follows:

[0188] 1H NMR(400MHz,Chloroform-d)δ9.58(d,J=2.5Hz,1H),9.27(d,J=2.3Hz,1H),8.84(dd,J=4.8,1.5Hz,1H),8.79(ddd,J=8.3, 2.4, 1.5Hz, 1H), 8.64 (dd, J = 4.9, 1.5Hz, 1H), 8.61 (ddd, J = 8.4, 2.6, 1.5Hz, 1H), 7.50 (dddd, J = 14.3, 8.4, 4.8, 0.7Hz, 2H).

[0189] This invention uses aromatic amines or aromatic heteroamines as raw materials. Through screening of catalysts and solvents, and using hydrogen peroxide as an oxidant, it achieves efficient and selective oxidation of aromatic amines or aromatic heteroamines to the corresponding azobenzene oxide compounds under mild conditions. The oxidant used in this method is green, environmentally friendly, and pollution-free. The catalyst is common, readily available, inexpensive, and has a significant catalytic effect. Furthermore, the reaction conditions are mild, the operation is simple, the cost is low, the rate is fast, the selectivity is high, and the product yield is high. This is a novel method for synthesizing azobenzene oxide compounds with good scientific research value and industrialization potential.

[0190] The above description is merely a preferred embodiment of the present invention and should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent application and the contents of the specification of the present invention should still fall within the scope of the patent of the present invention.

Claims

1. A green synthesis method for azobenzene compounds, characterized in that: In an organic solvent, using aromatic amines or aromatic heteroamines as raw materials, and utilizing a reaction system composed of an oxidant and a catalyst, aromatic amines are selectively oxidized to the corresponding azo compounds. The specific synthetic route is as follows: ； The catalyst is NaF; The oxidant is hydrogen peroxide; The R and R′ are selected from one or more of hydrogen, halogen, -CF3, -OCF3, -CHF2, -CN, ester, alkyl, alkoxy, and aryl; Ar is an aromatic ring or aromatic heterocycle, the aromatic ring is selected from a benzene ring or a naphthyl ring, and the aromatic heterocycle is selected from pyridine, thiophene, furan, pyridazine, pyrimidine, pyrazine, oxazole, isoxazole, thiazole, isothiazole, quinoline, benzothiazole, or isoquinoline; The organic solvent is one or more of MeCN, DMF, DMSO, DCE, and EtOH.

2. The green synthesis method for azobenzene compounds according to claim 1, characterized in that: The molar amount of the catalyst is 0.1-3 equiv of aromatic amine or aromatic heteroamine.

3. The green synthesis method for azobenzene compounds according to claim 1, characterized in that: The molar amount of the oxidant is 3-20 equiv of aromatic amine or aromatic heteroamine.

4. The green synthesis method for azobenzene compounds according to claim 1, characterized in that: The mass concentration of the hydrogen peroxide is ≥30%.

5. The green synthesis method for an azobenzene compound according to claim 1, characterized in that: The reaction temperature is room temperature rt-100℃.

6. The green synthesis method for azobenzene compounds according to claim 1, characterized in that: The reaction time is 1h-36h.

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