Method for preparing nitro-aromatic compounds

Abstract

The invention discloses a method for preparing a nitro-aromatic compound, which comprises the following steps: dissolving aromatic hydrocarbon, a catalyst and ferric nitrate in a solvent, reacting for 10-24 hours in an air atmosphere and under illumination, and after the reaction is finished, carrying out column chromatography separation to obtain the nitro-aromatic compound. According to the method, the nitroaromatic compounds are directly prepared through photocatalytic green nitration, and the method is easy to operate, environmentally friendly, free of the problem of corrosivity and high in yield.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for preparing nitroaromatic compounds. Background Technology

[0002] The nitro group is an important functional group in organic compounds, and nitroaromatics have wide applications in dyes, explosives, pharmaceuticals, and materials. Studies have shown that nitroaromatic fragments such as nitrofurans and nitroimidazoles have great potential for treating various infectious parasitic and bacterial diseases. The nitro group can be readily converted into amines, amides, and heterocyclic compounds, which are widely used in the production of dyes, plastics, and fragrances. Therefore, developing methods for preparing nitroaromatics is essential.

[0003] The nitration of aromatics has long been a focus of attention in academia and industry. Traditional methods utilize a "mixed acid" system. This method requires large amounts of excess concentrated nitric acid and concentrated sulfuric acid, resulting in drawbacks such as environmental unfriendliness, severe equipment corrosion, and dangerous operation. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing nitroaromatic compounds, in order to solve the problems of high difficulty, environmental unfriendliness, and corrosiveness to equipment in the preparation of nitroaromatic compounds by existing technologies, and to realize the direct preparation of nitroaromatic compounds through photocatalysis.

[0005] To achieve the above objectives, this invention provides a method for preparing nitroaromatic compounds. Under acid-free conditions, aromatic compounds are prepared by photocatalytic green nitration reaction with ferric nitrate nonahydrate. The specific steps are as follows:

[0006]

[0007] Aromatic hydrocarbons, a catalyst, and ferric nitrate nonahydrate are dissolved in a solvent and reacted in air at 0-80°C, preferably 20-50°C; the reaction time is 10-24 hours, preferably 15-20 hours; after the reaction is completed, nitroaromatic compounds are obtained by column chromatography.

[0008] Aromatic hydrocarbons are all-carbon aromatic rings with substituents. The substituents on the benzene ring are methoxy, ester, methyl, phenoxy, 2-hydroxyethoxy, etc.; they can also be heterocycles, including pyridine rings, and the amount used is 0.1-10 mmol; the air gas pressure is 1-10 bar, preferably 1-5 bar.

[0009] The molar ratio of ferric nitrate nonahydrate to aromatic hydrocarbons is 1:1-5.

[0010] The catalyst is one or more of riboflavin, tetraacetylated riboflavin, and sodium riboflavin dihydrate, preferably tetraacetylated riboflavin; the amount of catalyst used is 1-10 mol% of the amount of aromatic hydrocarbon, preferably 5-10 mol%.

[0011] The illumination is one of the following: blue light, green light, violet light, red light, ultraviolet light, and white light, with blue light being preferred; the illumination intensity is 1-10 mW / cm². 2 3-8mW / cm is preferred 2 .

[0012] The solvent is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, and water, preferably acetonitrile; the amount of solvent used is 0.1-3.0 mL per 0.2 mmol of aromatic hydrocarbon, preferably 0.5-2.0 mL.

[0013] The eluent used in column chromatography was petroleum ether:ethyl acetate in a ratio of 10:1, and the silica gel had a particle size of 200-300 mesh.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0015] This invention utilizes a novel photocatalyst for the green nitration of aromatics, using nitrates as the nitro source to react aromatics with ferric nitrate nonahydrate to prepare nitroaromatic compounds. This method is simple, has mild reaction conditions, is low in cost, environmentally friendly, does not cause equipment corrosion, and has a high yield, thus realizing the direct photocatalytic preparation of nitroaromatic compounds. Attached Figure Description

[0016] Figure 1 Infrared absorption spectrum of tetraacetylated riboflavin;

[0017] Figure 2 Tetraacetylated riboflavin UV-Vis absorption spectrum;

[0018] Figure 3 THC NMR spectrum of tetraacetylated riboflavin. Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments, but this does not limit the present invention in any way.

[0020] Unless otherwise specified, the instruments, reagents, and materials used in the following embodiments are all conventional instruments, reagents, and materials already available in the prior art and can be obtained through legitimate commercial channels. Unless otherwise specified, the experimental methods and detection methods used in the following embodiments are all conventional experimental methods and detection methods already available in the prior art.

[0021] Synthesis of the catalyst tetraacetyl riboflavin: 0.5 g of riboflavin was added to 40 mL of a solution of glacial acetic acid and acetic acid in a volume ratio of 1:1. Then, 0.1 mL of 70% perchloric acid was added dropwise, and the reaction mixture was stirred at 40 °C under an argon atmosphere for 1 hour. The mixture was then cooled to 0-4 °C in an ice bath, diluted with 40 mL of 0-4 °C cold water, and extracted twice with 40 mL of dichloromethane. The combined organic phases (dichloromethane phase) were washed twice, successively with 50 mL of water and saturated sodium bicarbonate solution. The organic phases were dried with anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation. The dried product yielded the catalyst tetraacetyl riboflavin.

[0022]

[0023] Through infrared absorption spectroscopy ( Figure 1 ), UV-Vis absorption spectrum ( Figure 2 ) and nuclear magnetic resonance hydrogen spectrum ( Figure 3 Experimental characterization of the product confirmed the successful synthesis of the above catalyst.

[0024] Example 1:

[0025] As shown in Table 1, the catalyst tetraacetyl riboflavin 0.01 mmol (5 mol% of the aromatic hydrocarbons), ferric nitrate nonahydrate 0.2 mmol (100 mol% of the aromatic hydrocarbons), aromatic hydrocarbons (0.2 mmol), and solvent acetonitrile (1.0 mL) were added to the photoreaction tube. The total amount of these substances in the photoreaction tube was 10% of its volume. Then, under normal atmospheric pressure and air atmosphere, at 30°C, blue light (8 mW / cm²) was applied. 2 The reaction was carried out for 18 hours. After the reaction was completed, the product was separated by column chromatography (the eluent in the column chromatography was petroleum ether: ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain a (i.e., 3a in Table 1) with a yield of 80%. The structure of the compound was identified by NMR (H1N and C1N spectra) (the structures of the aromatic raw materials and products are shown in Table 1).

[0026] The test data is as follows:

[0027] (3a): 34.4 mg, yellow solid, yield: 80%.

[0028] 1 H NMR (400MHz, CDCl3) δ8.23–8.15(m,2H),7.51–7.36(m,2H),7.29–7.20(m,1H),7.13–7.05(m,2H),7.05–6.97(m,2H).

[0029] 13C NMR (101MHz, CDCl3) δ163.5,154.9,130.5,126.1,125.6,120.7,117.2.

[0030] Example 2:

[0031] As shown in Table 1, the following were added to the photoreaction tube: 0.01 mmol of tetraacetylated riboflavin catalyst (5 mol% of the aromatic hydrocarbons), 0.2 mmol of ferric nitrate nonahydrate (100 mol% of the aromatic hydrocarbons), aromatic hydrocarbons (0.2 mmol), and 1.0 mL of acetonitrile solvent. The total amount of these substances in the photoreaction tube was 10% of the reactor volume. The reaction was then carried out under normal atmospheric pressure and air atmosphere at 30°C, using blue light (8 mW / cm²). 2 The reaction was carried out for 18 hours. After the reaction was completed, the product was separated by column chromatography (the eluent in the column chromatography was petroleum ether: ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain b (i.e. 3b in Table 1) with a yield of 70%. The structure of the compound was identified by NMR (H1N and C1N spectra) (the structures of the aromatic raw materials and products are shown in Table 1).

[0032] The test data is as follows:

[0033] (3b): 23.4 mg, yellow solid, yield: 70%.

[0034] 1 H NMR (400MHz, CDCl3) δ7.88 (dd, J=8.6, 2.3Hz, 1H), 7.65 (d, J=2.3Hz, 1H), 6.86 (d, J=8.6Hz, 1H), 6.14 (s, 2H).

[0035] 13 C NMR (101MHz, CDCl3) δ153.3,148.4,120.0,107.7,104.6,103.2,103.2.

[0036] Example 3:

[0037] As shown in Table 1, the following were added to the photoreaction tube: 0.01 mmol of tetraacetylated riboflavin catalyst (5 mol% of the aromatic hydrocarbons), 0.2 mmol of ferric nitrate nonahydrate (100 mol% of the aromatic hydrocarbons), aromatic hydrocarbons (0.2 mmol), and 1.0 mL of acetonitrile solvent. The total amount of these substances in the photoreaction tube was 10% of the reactor volume. The reaction was then carried out under normal atmospheric pressure and air atmosphere at 30°C, using blue light (8 mW / cm²). 2The reaction was carried out for 18 hours. After the reaction was completed, the compound was separated by column chromatography (the eluent in the column chromatography was petroleum ether: ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain c (i.e., 3c in Table 1) with a yield of 72%. The structure of the compound was identified by NMR (H1N and C1N spectra) (the structures of the aromatic raw materials and products are shown in Table 1).

[0038] The test data is as follows:

[0039] (3c): 28.4 mg, yellow solid, yield: 72%.

[0040] 1 H NMR (400MHz, CDCl3) δ7.63(s,1H),6.70(s,1H),3.95(s,3H),3.91(s,3H),2.60(s,3H).

[0041] 13 C NMR (101MHz, CDCl3) δ152.5,146.5,140.6,128.6,113.4,107.5,55.8,55.8,20.9.

[0042] Example 4:

[0043] As shown in Table 1, the following were added to the photoreaction tube: 0.01 mmol of tetraacetylated riboflavin catalyst (5 mol% of the aromatic hydrocarbons), 0.2 mmol of ferric nitrate nonahydrate (100 mol% of the aromatic hydrocarbons), aromatic hydrocarbons (0.2 mmol), and 1.0 mL of acetonitrile solvent. The total amount of these substances in the photoreaction tube was 10% of the reactor volume. The reaction was then carried out under normal atmospheric pressure and air atmosphere at 30°C, using blue light (8 mW / cm²). 2 The reaction was carried out for 18 hours. After the reaction, the product was separated by column chromatography (the eluent in the column chromatography was petroleum ether: ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain d (i.e. 3d in Table 1) with a yield of 95%. The structure of the compound was identified by NMR (H1N and C1N spectra) (the structures of the aromatic raw materials and products are shown in Table 1).

[0044] The test data is as follows:

[0045] (3d): 45.8 mg, yellow solid, yield: 95%.

[0046] 1 H NMR (400MHz, CDCl3) δ7.43(s,1H),7.06(s,1H),3.96(s,3H),3.95(s,3H),3.88(s,3H).

[0047] 13C NMR (101MHz, CDCl3) δ166.4,152.6,150.5,141.3,121.7,110.9,107.1,56.7,56.7,53.3,29.8.

[0048] Example 5:

[0049] As shown in Table 1, the following were added to the photoreaction tube: 0.01 mmol of tetraacetylated riboflavin catalyst (5 mol% of the aromatic hydrocarbons), 0.2 mmol of ferric nitrate nonahydrate (100 mol% of the aromatic hydrocarbons), aromatic hydrocarbons (0.2 mmol), and 1.0 mL of acetonitrile solvent. The total amount of these substances in the photoreaction tube was 10% of the reactor volume. The reaction was then carried out under normal atmospheric pressure and air atmosphere at 30°C, using blue light (8 mW / cm²). 2 The reaction was carried out for 18 hours. After the reaction was completed, the product was separated by column chromatography (the eluent in the column chromatography was petroleum ether: ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain e (i.e., 3e in Table 1) with a yield of 46%. The structure of the compound was identified by NMR (H1N and C1N spectra) (the structures of the aromatic raw materials and products are shown in Table 1).

[0050] The test data is as follows:

[0051] (3e): 17.0 mg, yellow solid, yield: 46%.

[0052] 1 H NMR (400MHz, CDCl3) δ8.34(d,J=8.8Hz,1H),6.37(d,J=8.8Hz,1H),4.12(s,3H),4.02(s,3H).

[0053] 13 C NMR (101MHz, CDCl3) δ163.5,154.9,130.5,126.1,125.6,120.7,117.2.

[0054] Table 1. Reaction results of different substituted aromatic hydrocarbons with ferric nitrate nonahydrate in Examples 1-5.

[0055]

[0056]

[0057] From the above examples, it can be seen that the target product can be obtained for aromatic hydrocarbons with phenoxy substitution (Example 1) and alkoxy disubstitution (Example 2); the target product can also be obtained when the substituent of the aromatic hydrocarbon is polysubstituted (Example 3); and the target product is obtained with good yield when the substituent of the aromatic hydrocarbon contains both an electron-withdrawing ester group and an electron-donating methoxy group (Example 4) and for heterocyclic aromatic hydrocarbons (Example 5). In summary, the chemical synthesis method of the present invention has a wide range of applicability to substrates.

[0058] Comparative Example 1

[0059] Keeping the other reaction conditions described in Example 1 unchanged (i.e., the operation process and conditions are the same as in Example 1), the difference is that the blue light in the reaction conditions is removed and replaced with no light, the yield of the target product p-nitrodiphenyl ether 3a is reduced to 0%, and a large amount of raw materials remain.

[0060] Comparative Example 2

[0061] Keeping the other reaction conditions described in Example 1 unchanged (i.e., the operation process and conditions are the same as in Example 1), the difference is that the catalyst for the reaction is removed and not added, and the yield of the target product p-nitrodiphenyl ether 3a is reduced to 0%. Furthermore, there is a significant surplus of raw materials.

[0062] Comparative Example 3

[0063] Keeping the other reaction conditions described in Example 1 unchanged (i.e., the operation process and conditions are the same as in Example 1), the difference is that the ferric nitrate nonahydrate in the reaction is changed to an equimolar amount of copper nitrate, the yield of the target product p-nitrodiphenyl ether 3a is reduced to 0%, and a large amount of raw materials remain.

[0064] Comparative Example 4

[0065] Keeping the other reaction conditions described in Example 1 unchanged (i.e., the operation process and conditions are the same as in Example 1), the difference is that: changing the air atmosphere in the reaction conditions to placing the system under a nitrogen atmosphere will result in a significant decrease in the yield of the target product p-nitrodiphenyl ether 3a to 40%, and a large amount of raw materials will remain.

[0066] Example 6: Synthesis of an anti-inflammatory nabumetone compound.

[0067] Add 0.01 mmol of tetraacetylated riboflavin (5 mol% of the aromatic hydrocarbons), 0.2 mmol of ferric nitrate nonahydrate (100 mol% of the aromatic hydrocarbons), 0.2 mmol of the aromatic hydrocarbon raw material (left side of the following formula), and 1.0 mL of acetonitrile (solvent) to a photoreaction tube. The total amount of these substances in the photoreaction tube is 10% of its volume. Then, in a normal atmospheric pressure atmosphere at 30°C, under blue light (8 mW / cm²), the reaction is carried out. 2The reaction was carried out for 18 hours. After the reaction, the compound was separated by column chromatography (the eluent was petroleum ether:ethyl acetate in a ratio of 10:1, and the silica gel particle size was 200-300 mesh) to obtain nabumetone. The structure of the compound was identified by NMR (1H NMR and 1C NMR), with a yield of 76%.

[0068]

[0069] This method can be used to synthesize nabumetone, a known drug molecule with anti-inflammatory properties.

[0070] For anyone skilled in the art, many possible variations and modifications can be made to the technical solutions of this invention, or equivalent embodiments can be modified based on the disclosed technical content, without departing from the scope of the technical solutions of this invention. Therefore, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of this invention without departing from the content of the technical solutions of this invention should still fall within the protection scope of the technical solutions of this invention.

Claims

1. A process for the preparation of a nitroarene compound, characterized in that, The method comprises the following steps: dissolving the aromatic hydrocarbon, the catalyst and the ferric nitrate in a solvent, and reacting under air atmosphere and light for 10-24 hours (preferably 12-22 hours, more preferably 16-20 hours) to obtain the nitro aromatic compound.

2. The method of claim 1, wherein, The aromatic hydrocarbon is one or more than two of a full-carbon aromatic ring or a heterocycle, wherein the aromatic ring or the heterocycle is unsubstituted or substituted with substituents, and the atoms in the ring are all carbon; The substituents are one or more than two of methoxy, ethoxy, propoxy, butoxy, C2-C8 ester group, methyl, ethyl, propyl, butyl, phenoxy, 2-hydroxyethoxy and 2-butanone; The heterocycle includes one or more than two of a pyridine ring, a pyrrole ring, a furan ring and a quinoline ring.

3. The method according to claim 1 or 2, wherein the aromatic hydrocarbon is one or more than two of the following general formulae R is one or more than two of methoxy, ethoxy, propoxy, butoxy, C2-C8 ester group, methyl, ethyl, propyl, butyl, phenoxy, 2-hydroxyethoxy and 2-butanone.

4. The method according to claim 1, wherein the ferric nitrate is ferric nitrate nonahydrate; The molar ratio of the aromatic hydrocarbon to the ferric nitrate is 1:1-5, preferably 1:1-4, and more preferably 1:1-2. The light is one of blue light, green light, purple light, red light, ultraviolet light and white light. The catalyst is one or more than two of riboflavin, tetraacetyl riboflavin and riboflavin phosphate sodium dihydrate; 5. The method of claim 1, wherein, The amount of the catalyst is 1-10 mol% of the amount of the aromatic hydrocarbon, preferably 2-8 mol%, and more preferably 3-6 mol%. The light intensity is 1-10 mW / cm 2 , preferably 2-8 mW / cm 2 , more preferably 3-6 mW / cm 2 .

6. The method of claim 1, wherein, The solvent is one or more than two of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide and water; The amount of the solvent is 0.1-3.0 ml (preferably 0.5-2.5 ml, and more preferably 1.0-2.0 ml) of the solvent per 0.2 mmol of the aromatic hydrocarbon.

7. The method of claim 1, wherein, The reaction temperature is 0-50℃, preferably 10-40℃, and more preferably 20-30℃; The separation mode is column chromatography separation; 8. The method of claim 1, wherein, The eluent in the column chromatography is petroleum ether: ethyl acetate in a ratio of 8-10:1, and the silica gel particle size is 200-300 mesh; The air gas pressure is 1-10 bar (preferably 1-8 bar, and more preferably 1-5 bar). The catalyst is tetraacetyl riboflavin in an amount of 3-6 mol% of the amount of the aromatic hydrocarbon, the ferric nitrate nonahydrate is in an amount of 100-200 mol% of the amount of the aromatic hydrocarbon, the solvent is acetonitrile, and the reaction is carried out under normal pressure air atmosphere and blue light for 16-20 hours to obtain p-nitrodiphenyl ether through column chromatography separation. The active ingredient of the medicine for preparing an anti-inflammatory medicine includes nabanedimethicone, and the specific reaction formula is as follows, 9. The method according to any of claims 1 or 5 or -8, characterized in that, ​ 10. The method of claim 1, wherein, ​

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