Electrochemical method for realizing nitration of N-substituted aniline by using sodium nitrite as nitro source

Abstract

The invention belongs to synthesis of organic compounds, and discloses an electrochemical method for nitrifying N-substituted aniline by using sodium nitrite as a nitro source, which specifically comprises the following steps: mixing N-substituted aniline as a starting material and sodium nitrite as a nitration reagent with a solvent, and reacting under the conditions of electrification and room temperature by using Pt (+) / Pt (-) as a positive electrode and a negative electrode. And after the reaction is finished, carrying out purification treatment to obtain a nitration product of N-substituted aniline. N-substituted aniline compounds with different structures are used as raw materials, sodium nitrite is used as a nitration reagent, and nitration products of the N-substituted aniline compounds are successfully obtained. According to the method, clean electric energy is used as driving force, use of strong acid reagents such as sulfuric acid and nitric acid in a traditional nitration reaction is avoided, the method has the advantages that the reagents are simple and easy to obtain, operation is easy and convenient, the reaction condition is mild, the yield is high, and environment friendliness is achieved, and a new green and efficient way is provided for nitration of aromatic amine compounds.

Description

Technical Field

[0001] The present invention relates to the synthesis of organic compounds, and in particular, to an electrochemical method for nitrating N-substituted anilines using sodium nitrite as a nitro source. Background Art

[0002] Nitroaromatic compounds or intermediates are important organic precursors for the synthesis of pharmaceuticals, dyes, explosives, and other high-value chemicals. Therefore, finding an efficient method to achieve the nitration reaction of aromatic derivatives has been a research topic of great concern to organic chemists. For example, flutamide can inhibit the binding of testosterone and DHT to androgen receptors and has been used to treat metastatic prostate cancer, while niclosamide exhibits strong anti-cestode activity. 2-Nitro-N-acylanilines are key intermediates for the synthesis of phenanthroimidazole derivatives, and such derivatives have significant antibacterial or antifungal properties.

[0003] Therefore, nitroanilines are considered an important organic precursor and have attracted extensive research by chemists. The methods reported in the current literature are as follows:

[0004] (1) Nitration of N-substituted anilines under strong acid conditions. For example, nitration of N-substituted anilines with NaNO3 under silica-supported sulfuric acid conditions (Baet, Y.S.; Kim, H. Bulletin of the Korean Chemical Society, 2007, 2(2): 407-408.); nitration of N-substituted anilines with wet carbon-based solid acid and NaNO3 under solvent-free conditions (Arash, S.; Abbas, Z.; Mohammad, H.K. Chinese Chemical Letters: English Edition, 2007.); nitration of N-substituted anilines with ammonium molybdate and nitric acid in chloroform (Sana, S.; Rajanna, K.C.; Ali, M.M. Cheminform, 2010, 31(19):); nitration of N-substituted anilines with nitric acid and sulfuric acid in water (Li, R.M.; Ji, W.H.; Gao, Q.S. 2011[2025-03-03].); nitration of N-substituted anilines with BiNaO3 in nitric acid, dichloroethane, and water (Sana, S.; Rajanna, K.C.; Reddy, K.R. Green & Sustainable Chemistry, 2012, 2(3).).

[0005] Although such reactions have successfully achieved the nitration of N-substituted anilines, they use strong acids such as sulfuric acid and nitric acid, resulting in the generation of a large amount of waste acid, which requires expensive costs to treat and is not environmentally friendly.

[0006] (2) The nitration reaction of N-substituted anilines is carried out under catalyst conditions. For example, the nitration reaction of N-substituted anilines with sodium nitrite is carried out under the conditions of catalytic enzymes (Kong, M.; Wang, K.; Dong, R. Enzyme and Microbial Technology, 2015, s 73–74: 34-43.). The nitration reaction of N-substituted anilines is carried out under the catalysis of sulfuric acid-functionalized silica-based magnetic core / shell nanocomposites (Maleki, A.; Aghaei, M.; Paydar, R. Journal of the Iranian Chemical Society, 2017, 14(2)). The nitration reaction of N-substituted anilines with sodium nitrate is carried out under the catalysis of iron oxide and with the assistance of ultrasound. (Maleki, A.; Aghaie, M. Ultrasonics Sonochemistry, 2017, 39: 534.). The regioselective nitration of N-substituted anilines with sodium nitrite is carried out in the presence of melamine trisulfonic acid (Albadi, J.; Shirinib, F.; Abedini, M. Arabian Journal of Chemistry, 2017, 10.). The nitration reaction of N-substituted anilines with nitrosylammonium tetrafluoroborate is carried out under the catalysis of silver nitrate (Sa, Li.; Wen, tao. Org. Biomol. Chem., 2023, 21, 9428).

[0007] Although the nitration reaction of N-substituted anilines has been successfully achieved in these reactions, the catalyst selectivity is poor. The existing catalysts may only be applicable to specific types of N-substituted anilines and have a poor catalytic effect on substrates with complex structures.

[0008] (3) The nitration reaction of N-substituted anilines is carried out under oxidant conditions. For example, the direct oxidative nitration of N-substituted anilines with sodium nitrite is carried out under the conditions of potassium peroxymonosulfate oxidant (Li, Y.; Li, L.; Yang, Y. Chemical Communications, 2014, 50(69): 9936-9938.). The direct nitration of N-substituted anilines with sodium nitrite is carried out under the conditions of iodine pentoxide oxidant (Shao, Y.; Huang, L. CN201910259994.1).

[0009] Although these reactions do not require complex catalysts, they require oxidants, which can lead to over-oxidation of the products and greatly increase the reaction difficulty. Summary of the Invention

[0010] In view of the above problems, the present invention provides an electrochemical method for nitrating N-substituted anilines using sodium nitrite as the nitro source. This method uses clean electrical energy as the driving force, avoiding the use of strong acid reagents such as sulfuric acid and nitric acid in traditional nitration reactions. At the same time, it does not require the use of oxidants and catalysts, nor the addition of electrolytes. This method has the characteristics of good universality of reaction conditions and high yields, and is insensitive to both air and water, providing a green and efficient new approach for the nitration of aromatic amine compounds.

[0011] Based on the electrochemical reaction conditions, the present invention generates free radicals by direct oxidation on the electrode surface and forms nitro compounds of N-substituted anilines through free radical coupling. The unique electronic environment also helps to study the electron transfer process in free radical reactions.

[0012] The specific method comprises the following steps: using N-substituted aniline compounds as starting materials, sodium nitrite as the nitrating reagent, mixing with a solvent, setting positive and negative electrodes, and reacting under the conditions of energization and room temperature. After the reaction, the nitration product of the N-substituted aniline compound is obtained through purification treatment;

[0013] The positive and negative electrode materials are each independently one of noble metals, transition metals, and carbon materials;

[0014] Among them, the general formula of the N-substituted aniline compound is:

[0015]

[0016] The structural formula of the obtained nitration product is:

[0017] In the formula: R1 and R2 are each independently selected from the following groups: hydrogen, C1-C3 alkyl, aryl; and R3 is selected from the following groups: hydrogen, C1-C4 alkyl, C1-C4 alkoxy, carbonyl functional group, halogen, aryl.

[0018] Preferably, in the formula: R1 is any one of hydrogen, methyl, ethyl, phenyl; R2 is any one of hydrogen, methyl, ethyl, phenyl; and R3 is any one of hydrogen, methyl, methoxy, tert-butyl, aldehyde group, ketone group, fluorine, chlorine, bromine, phenyl.

[0019] Preferably, the N-substituted aniline is any one of the following compounds:

[0020]

[0021] Preferably, the molar ratio of the N-substituted aniline to sodium nitrite is 1:(1.0 - 3.0).

[0022] Preferably, the solvent is one of acetonitrile, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, ethanol, methanol, and acetone, which is used alone or in combination with water. When used in combination, the volume ratio of the organic solvent to water is preferably 4:1.

[0023] Preferably, the positive and negative electrodes are specifically one of Pt(+) / Pt(-), Pt(+) / C(-), Pt(+) / Ni(-), C(+) / Pt(-), Fe(+) / Pt(-); most preferably Pt(+) / Pt(-).

[0024] Preferably, the concentration of the N-substituted aniline nitro compound is 0.06 - 0.12 mol / L.

[0025] Preferably, the current passed is 5 - 20 mA.

[0026] Specifically, the reaction temperature is room temperature and the reaction time is 5 - 8 hours.

[0027] Specifically, the purification treatment includes: washing with sodium thiosulfate solution, extraction with ethyl acetate, washing with brine, drying with anhydrous sodium sulfate, concentration under reduced pressure, and column chromatography.

[0028] The specific mechanism may be: N-substituted aniline and sodium nitrite are respectively oxidized at the anode to generate N-substituted aniline radicals and nitro radicals, and the N-substituted aniline nitro compound is formed through the cross-coupling of the radicals.

[0029] Through the above technical solutions, the present invention achieves the following beneficial effects:

[0030] 1. The present invention uses clean electric energy as the driving force, avoiding the use of strong acid reagents such as sulfuric acid and nitric acid in traditional nitration reactions. It has the advantages of simple and easily available reagents, simple operation, mild reaction conditions, high yield, and environmental friendliness, providing a new green and efficient way for the nitration of aromatic amine compounds.

[0031] 2. The present invention uses N-substituted anilines with different structures as raw materials, sodium nitrite as the nitration reagent, preferably positive and negative electrodes, and reacts under set current and room temperature conditions, successfully realizing the nitration reaction of N-substituted aniline compounds. This method has simple and easily available reagents, simple operation, high atom economy, and broadens the nitration methods of N-substituted anilines. Specific Embodiments

[0032] The following details the specific embodiments of the present invention. It should be understood that the specific embodiments described herein are only for the purpose of illustrating and explaining the present invention, and are not intended to limit the present invention.

[0033] In the following examples, unless otherwise specified, the methods are all conventional methods. Some of the raw materials are obtained from public commercial channels, and some are prepared by known methods. In the column chromatography step of the following examples, the packing material of the chromatography column used is silica gel with a mesh size of 200-300, and the specification is a diameter of 2 cm × a height of 30 cm.

[0034] Example 1

[0035] The nitration product of N,N-dimethyl-p-toluidine and sodium nitrite as shown in Formula III-aa has the following synthetic route:

[0036]

[0037] The above reaction equation is the synthesis of the nitration reaction of N,N-dimethyl-p-toluidine and sodium nitrite:

[0038] Add N,N-dimethyl-p-toluidine (69.0 mg, 0.5 mmol), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile: water = 4 mL: 1 mL with a total volume of 5 mL to the reactor in sequence. Use Pt(+) / Pt(-) as the positive and negative electrodes, with a current of 10 mA, and react at room temperature for 5 h. After the reaction, wash with sodium thiosulfate solution, extract with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography to obtain 73.9 mg of yellow solid N,N,4-trimethyl-2-nitroaniline shown in Formula III-aa, with a yield of 82%.

[0039] The results of structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 2.4 Hz, 1H), 7.23 (dd, J = 2.4, 2.0 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 2.84 (s, 6H), 2.30 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 144.3, 139.6, 134.2, 128.3, 126.4, 118.5, 42.8, 20.0.

[0040] The synthesized compound was identified by structure as the target compound N,N,4-trimethyl-2-nitroaniline shown in Formula III-aa.

[0041] In the above reaction, under the condition that other conditions remain unchanged, only study the effect of current intensity on the yield of N,N,4-trimethyl-2-nitroaniline:

[0042] When not powered on, N,N,4-trimethyl-2-nitroaniline is not generated; when using a current of 5 mA, the yield of the product N,N,4-trimethyl-2-nitroaniline is 55%; when using a current of 15 mA, the yield of the product N,N,4-trimethyl-2-nitroaniline is 74%; when using a current of 20 mA, the yield of the product N,N,4-trimethyl-2-nitroaniline is 51%.

[0043] Under the condition that other conditions remain unchanged, study the influence of electrode materials on the yield:

[0044] When using Pt(+) / C(-) as the positive and negative electrodes, the yield of the product N,N,4-trimethyl-2-nitroaniline is 54%; when using Pt(+) / Ni(-) as the positive and negative electrodes, the yield of the product N,N,4-trimethyl-2-nitroaniline is 79%; when using C(+) / Pt(-) as the positive and negative electrodes, for the product; when using Fe(+) / Pt(-) as the positive and negative electrodes, the yield of the product N,N,4-trimethyl-2-nitroaniline is 59%.

[0045] Under the condition that other conditions remain unchanged, study the influence of the solvent system on the yield:

[0046] When selecting tetrahydrofuran: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 63%; when selecting N,N-dimethylformamide: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 54%; when selecting dimethyl sulfoxide: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 67%; when selecting ethanol: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 49%; when selecting methanol: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 35%; when selecting acetone: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 72%; when selecting acetonitrile: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 41%; when selecting acetonitrile: water volume ratio of 4 mL: 1 mL respectively, and the total amount of 5 mL as the solvent, the yield of the product N,N,4-trimethyl-2-nitroaniline is 59%.

[0047] Under the condition that other conditions remain unchanged, study the influence of the type of electrolyte on the yield:

[0048] Without additional electrolyte: 82% yield. With other conditions unchanged, when adding tetrabutylammonium iodide (36.9 mg, 0.1 mmol) as the electrolyte, the yield of the product N,N,4-trimethyl-2-nitroaniline is 70%; when adding tetrabutylammonium tetrafluoroborate (32.9 mg, 0.1 mmol) as the electrolyte, the yield of the product N,N,4-trimethyl-2-nitroaniline is 73%; when adding ammonium hexafluorophosphate (38.7 mg, 0.1 mmol) as the electrolyte, the yield of the product N,N,4-trimethyl-2-nitroaniline is 75%; when adding lithium perchlorate (10.6 mg, 0.1 mmol) as the electrolyte, the yield of the product N,N,4-trimethyl-2-nitroaniline is 81%.

[0049] Effect of reaction time on the yield under other unchanged conditions

[0050] When the reaction time is selected as 3 h, the yield of the product N,N,4-trimethyl-2-nitroaniline is 48%; when the reaction time is selected as 7 h, the yield of the product N,N,4-trimethyl-2-nitroaniline is 56%.

[0051] Example 2

[0052] A nitration product of N,N-dimethyl-p-methoxyaniline and sodium nitrite as shown in Formula III-ba, and its synthesis route is as follows:

[0053]

[0054] The above reaction equation is the synthesis of the nitration of N,N-dimethyl-p-methoxyaniline and sodium nitrite:

[0055] Add N,N-dimethyl-p-methoxyaniline (77.2 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile: water = 4 mL: 1 mL with a total volume of 5 mL into the reactor in sequence, use Pt(+) / Pt(-) as the positive and negative electrodes, react at a current of 10 mA and room temperature for 5 h. After the reaction is completed, wash with sodium thiosulfate solution, extract with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography to obtain 89.2 mg of yellow oily 4-methoxy-N,N-dimethyl-2-nitroaniline shown in Formula III-ba, with a 91% yield.

[0056] The structural confirmation results are as follows: 1 H NMR(400MHz,CDCl3)δ7.30(s,1H),7.08 - 7.03(m,2H),3.77(s,3H),2.80(s,6H). 1313C NMR (100 MHz, CDCl3) δ 152.7, 141.45, 141.1, 120.9, 120.8, 109.6, 55.9, 43.5.

[0057] The synthesized compound was identified as the target compound 4-methoxy-N,N-dimethyl-2-nitroaniline shown in III-ba through structure identification.

[0058] Example 3

[0059] A nitration product of N,N-dimethyl-p-tert-butylaniline and sodium nitrite as shown in formula III-ca, and its synthetic route is as follows:

[0060]

[0061] The above reaction equation is the synthesis of the nitration of N,N-dimethyl-p-tert-butylaniline and sodium nitrite:

[0062] Add N,N-dimethyl-p-tert-butylaniline (90.3 mg), sodium nitrite (104.5 mg, 1.5 mmol) to the reactor in sequence, with a total amount of 5 mL of acetonitrile:water = 4 mL:1 mL, Pt(+) / Pt(-) as the positive and negative electrodes, a current of 10 mA, react at room temperature for 5 h. After the reaction, wash with sodium thiosulfate solution, extract with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography to obtain 88.8 mg of yellow oily 4-tert-butyl-N,N-dimethyl-2-nitroaniline shown in formula III-ca, with a yield of 80%.

[0063] The results of structure confirmation are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 2.8 Hz, 1H), 7.46 (dd, J = 2.4, 2.4 Hz, 1H), 7.00 (d, J = 8.8 Hz, 1H), 2.86 (s, 6H), 1.30 (s, 9H). 13 13C NMR (100 MHz, CDCl3) δ 144.1, 141.7, 139.4, 130.7, 123.0, 118.1, 42.6, 34.0, 31.1.

[0064] The synthesized compound was identified as the target compound 4-tert-butyl-N,N-dimethyl-2-nitroaniline shown in III-ca through structure identification.

[0065] Example 4

[0066] A nitration product of N,N-dimethyl-p-fluoroaniline and sodium nitrite as shown in formula III-da, and its synthetic route is as follows:

[0067]

[0068] The above reaction equation is the synthesis of N,N-dimethyl-p-fluoroaniline by nitration with sodium nitrite:

[0069] Add N,N-dimethyl-p-fluoroaniline (71 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL, Pt(+) / Pt(-) as the positive and negative electrodes, a current of 10 mA, and react at room temperature for 5 h. After the reaction, wash with sodium thiosulfate solution, extract with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography to obtain 47 mg of 4-fluoro-N,N-dimethyl-2-nitroaniline shown as yellow solid formula III-da, with a 51% yield.

[0070] The results of structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 8.2, 3.1 Hz, 1H), 7.19 (ddd, J = 10.2, 7.2, 3.1 Hz, 1H), 7.04 (dd, J = 9.2, 4.6 Hz, 1H), 2.85 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 155.9, 153.5, 143.4, 143.3, 139.4, 139.3, 121.0, 120.7, 120.1, 120.0, 113.1, 112.9, 43.0.

[0071] The synthesized compound was identified as 4-fluoro-N,N-dimethyl-2-nitroaniline shown as the target compound III-da.

[0072] Example 5

[0073] A nitration product of N,N-dimethyl-p-chloroaniline as shown in formula III-ea, and its synthetic route is as follows:

[0074]

[0075] The above reaction equation is the synthesis of N,N-dimethyl-p-chloroaniline by nitration with sodium nitrite:

[0076] To the reactor, N,N-dimethyl-p-chloroaniline (79.4 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL were added successively. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 54 mg of 4-chloro-N,N-dimethyl-2-nitroaniline shown as formula III-ea, with a yield of 54%.

[0077] The results of structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 2.8 Hz, 1H), 7.36 (dd, J = 3.6, 4.4 Hz, 1H), 6.96 (d, J = 9.6 Hz, 1H), 2.89 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 144.9, 138.8, 133.2, 126.2, 122.3, 119.3, 42.5.

[0078] The synthesized compound was identified as 4-chloro-N,N-dimethyl-2-nitroaniline shown as the target compound III-ea.

[0079] Example 6

[0080] A nitration product of N,N-dimethyl-p-bromoaniline and sodium nitrite as shown in formula III-fa, and its synthetic route is as follows:

[0081]

[0082] The above reaction equation is the synthesis of the nitration of N,N-dimethyl-p-bromoaniline and sodium nitrite:

[0083] To the reactor, N,N-dimethyl-p-bromoaniline (102 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL were added successively. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 68 mg of 4-bromo-N,N-dimethyl-2-nitroaniline shown as formula III-fa, with a yield of 56%.

[0084] The results of structure confirmation are as follows: 11H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 2.4 Hz, 1H), 7.47 (dd, J = 9.0, 2.4 Hz, 1H), 6.90 (d, J = 9.0 Hz, 1H), 2.89 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 145.2, 135.9, 133.9, 129.1, 119.5, 108.6, 42.3.

[0085] The synthesized compound was identified as 4-bromo-N,N-dimethyl-2-nitroaniline shown in the target compound III-fa through structure identification.

[0086] Example 7

[0087] A nitration product of p-(N,N-dimethyl)benzaldehyde and sodium nitrite as shown in formula III-ga has the following synthetic route:

[0088]

[0089] The above reaction equation is the synthesis of the nitration of p-(N,N-dimethyl)benzaldehyde and sodium nitrite:

[0090] To the reactor were successively added p-(N,N-dimethyl)benzaldehyde (75.3 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL, Pt(+) / Pt(-) as the positive and negative electrodes, the current was 10 mA, and the reaction was carried out at room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 54.3 mg of orange solid 4-(dimethylamino)-3-nitrobenzaldehyde shown in formula III-ga, with a yield of 56%.

[0091] The results of structure confirmation are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.80 (s, 1H), 8.25 (d, J = 2.1 Hz, 1H), 7.88 (dd, J = 8.9, 2.0 Hz, 1H), 7.06 (d, J = 8.9 Hz, 1H), 3.03 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 188.6, 149.3, 137.0, 132.3, 131.0, 125.4, 117.3, 42.3.

[0092] The synthesized compound was identified as 4-(dimethylamino)-3-nitrobenzaldehyde shown in the target compound III-ga through structure identification.

[0093] Example 8

[0094] A nitration product of (N,N-dimethyl) acetophenone as shown in Formula III-ha, and its synthetic route is as follows:

[0095]

[0096] The above reaction equation is the synthesis of nitration of (N,N-dimethyl) acetophenone with sodium nitrite:

[0097] Add (N,N-dimethyl) acetophenone (83.3 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile: water = 4 mL: 1 mL with a total volume of 5 mL, Pt(+) / Pt(-) as the positive and negative electrodes, the current is 10 mA, and the reaction is carried out at room temperature for 5 h. After the reaction, it is washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 60.3 mg of yellow solid 1-(4-(dimethylamino)-3-nitrophenyl) ethanone shown in Formula III-ha, with a 58% yield.

[0098] The results of structure confirmation are as follows: 1 H NMR(400MHz,CDCl3)δ8.36(d,J=1.6Hz,1H),7.99(dd,J=9.0,2.2Hz,1H),7.01(d,J=8.8Hz,1H),3.04(s,6H),2.54(s,3H). 13 CNMR(100MHz,CDCl3)δ194.90,148.53,136.71,132.48,128.57,125.75,116.81,41.18,26.09.

[0099] The synthesized compound was identified by structure as the target compound 1-(4-(dimethylamino)-3-nitrophenyl) ethanone shown in Formula III-ha.

[0100] Example 9

[0101] A nitration product of methyl 4-dimethylaminobenzoate and sodium nitrite, and its synthetic route is as follows:

[0102]

[0103] The above reaction equation is the synthesis of nitration of methyl 4-dimethylaminobenzoate with sodium nitrite:

[0104] Methyl 4-(dimethylamino)benzoate (91.4 mg), sodium nitrite (104.5 mg, 1.5 mmol) were successively added to a reactor, with acetonitrile:water = 4 mL:1 mL and a total volume of 5 mL. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 71.7 mg of the yellow solid 4-(dimethylamino)-3-nitrobenzoate shown in formula III-ia, with a yield of 64%.

[0105] The results of structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 8.01 (d, J = 9.0 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 3.89 (s, 3H), 2.99 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 148.4, 137.0, 133.7, 129.2, 118.1, 116.6, 52.1, 42.1.

[0106] The synthesized compound was identified as the target compound 4-(dimethylamino)-3-nitrobenzoate shown in formula III-ia by structure determination.

[0107] Example 10

[0108] The nitration product of N-methyl-p-toluidine and sodium nitrite as shown in formula III-ja has the following synthetic route:

[0109]

[0110] The above reaction equation is the synthesis of the nitration of N-methyl-p-toluidine and sodium nitrite:

[0111] N-Methyl-p-toluidine (62.5 mg), sodium nitrite (104.5 mg, 1.5 mmol) were successively added to a reactor, with acetonitrile:water = 4 mL:1 mL and a total volume of 5 mL. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 20 mg of the orange solid N,4-dimethyl-2-nitroaniline shown in formula III-ja, with a yield of 24%.

[0112] The results of structure confirmation are as follows: 11H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.93 (brs, NH, 1H), 7.27 (d, J = 11.2 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 3.00 (d, J = 5.2 Hz, 3H), 2.25 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 144.6, 137.8, 131.4, 125.9, 124.6, 113.3, 29.7, 19.9。

[0113] The synthesized compound was identified as the target compound N,4-dimethyl-2-nitroaniline shown in Compound III-ja through structural identification.

[0114] Example 11

[0115] The nitration product of 4-methoxy-N-methylaniline and sodium nitrite, as shown in Formula III-ka, has the following synthetic route:

[0116]

[0117] The above reaction equation is the synthesis of the nitration of 4-methoxy-N-methylaniline and sodium nitrite:

[0118] 4-Methoxy-N-methylaniline (70.7 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile: water = 4 mL: 1 mL with a total volume of 5 mL were successively added to the reactor. Pt(+) / Pt(-) were used as the positive and negative electrodes, the current was 10 mA, and the reaction was carried out at room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 24.6 mg of orange solid N-methyl-4-methoxy-2-nitroaniline shown in Formula III-ka, with a yield of 27%.

[0119] The results of structural confirmation are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.97 (brs, NH, 1H), 7.59 (d, J = 1.6 Hz, 1H), 7.19 (dd, J = 1.6, 4.8 Hz, 1H), 6.83 (d, J = 10.8 Hz, 1H), 3.79 (s, 3H), 3.01 (d, J = 6.4 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 149.4, 142.4, 130.7, 127.4, 114.7, 106.8, 55.8, 29.9。

[0120] The synthesized compound was identified structurally as the target compound N-methyl-4-methoxy-2-nitroaniline shown as III-ka.

[0121] Example 12

[0122] The nitration product of 4-fluoro-N-methylaniline and sodium nitrite as shown in formula III-la has the following synthetic route:

[0123]

[0124] The above reaction equation is the synthesis of the nitration of 4-fluoro-N-methylaniline with sodium nitrite:

[0125] 4-Fluoro-N-methylaniline (63.8 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile: water = 4 mL: 1 mL with a total volume of 5 mL, Pt(+) / Pt(-) as the positive and negative electrodes, a current of 10 mA, and the reaction was carried out at room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 21.3 mg of yellow solid N-methyl 4-fluoro-2-nitroaniline shown as formula III-la, with a 25% yield.

[0126] The results of structural confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.94 (brs, NH, 1H), 7.90 (dd, J = 3.2, 3.2 Hz, 1H), 7.30 - 7.25 (m, 1H), 6.84 (dd, J = 4.8, 4.4 Hz, 1H), 3.03 (d, J = 4.8 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 153.5, 151.2, 143.5, 125.2, 124.9, 114.7, 114.6, 112.0, 111.8, 29.9.

[0127] The synthesized compound was identified structurally as the target compound N-methyl 4-fluoro-2-nitroaniline shown as III-la.

[0128] Example 13

[0129] The nitration product of 4-bromo-N-methylaniline and sodium nitrite as shown in formula III-ma has the following synthetic route:

[0130]

[0131] The above reaction equation is the synthesis of the nitration of 4-bromo-N-methylaniline with sodium nitrite:

[0132] 4-Bromo-N-methylaniline (95.5 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL were successively added to the reactor. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 34.5 mg of orange solid N-methyl-4-bromo-2-nitroaniline shown in formula III-ma, with a yield of 30%.

[0133] The results of structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 1.2 Hz, 1H), 7.95 (brs, NH, 1H), 7.49 (dd, J = 2.4, 2.4 Hz, 1H), 6.69 (d, J = 9.2 Hz, 1H), 2.91 (d, J = 4.0 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 145.2, 139.0, 132.1, 128.8, 115.1, 106.3, 29.8.

[0134] The synthesized compound was identified by structure as N-methyl-4-bromo-2-nitroaniline shown in the target compound III-ma.

[0135] Example 14

[0136] A nitration reaction was carried out between N,N-diethyl-p-toluidine shown in formula III-na and sodium nitrite, and its synthetic route is as follows:

[0137]

[0138] The above reaction equation is the synthesis of the nitration reaction between N,N-diethyl-p-toluidine and sodium nitrite:

[0139] N,N-Diethyl-p-toluidine (83.3 mg), sodium nitrite (104.5 mg, 1.5 mmol), acetonitrile:water = 4 mL:1 mL with a total volume of 5 mL were successively added to the reactor. Pt(+) / Pt(-) were used as the positive and negative electrodes, and the reaction was carried out at a current of 10 mA and room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 81.1 mg of yellow oily N,N-diethyl-4-methyl-2-nitroaniline shown in formula III-na, with a yield of 78%.

[0140] The results of structure confirmation are as follows: 11H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 1.2 Hz, 1H), 7.25 (dd, J = 2.4, 2.4 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 3.10 (q, J = 21.6 Hz, 4H), 2.32 (s, 3H), 1.04 (t, J = 14 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 145.3, 141.9, 133.1, 131.6, 124.9, 123.2, 47.3, 20.3, 12.6。

[0141] The synthesized compound was identified as the target compound III - na, N,N - diethyl - 4 - methyl - 2 - nitroaniline.

[0142] Example 15

[0143] The nitration product of 4,4 - dimethyldiphenylamine and sodium nitrite as shown in formula III - oa has the following synthetic route:

[0144]

[0145] The above reaction equation is for the synthesis of the nitration product of 4,4 - dimethyldiphenylamine and sodium nitrite:

[0146] 4,4 - Dimethyldiphenylamine (100.7 mg), sodium nitrite (104.5 mg, 1.5 mmol) were successively added to the reactor, with a total of 5 mL of acetonitrile:water = 4 mL:1 mL, Pt(+) / Pt(-) as the positive and negative electrodes, a current of 10 mA, and the reaction was carried out at room temperature for 5 h. After the reaction, it was washed with sodium thiosulfate solution, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 61.7 mg of orange solid 4 - methyl - 2 - nitro - N - (p - tolyl)aniline shown in formula III - oa, with a 51% yield.

[0147] The results of structure confirmation are as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.35 (brs, NH, 1H), 7.98 (s, 1H), 7.20 - 7.13 (m, 5H), 7.09 (d, J = 8.8 Hz, 1H), 2.36 (s, 3H), 2.28 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 141.6, 137.1, 136.3, 135.2, 132.6, 130.2, 129.8, 126.8, 125.8, 124.4, 117.8, 116.0, 20.0, 20.1。

[0148] The compound synthesized through structural identification is the target compound 4-methyl-2-nitro-N-(p-tolyl)aniline shown as Compound III-oa.

[0149] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0150] In addition, it should be noted that, among the various specific technical features described in the above specific embodiments, without conflict, they can be combined in any suitable manner. To avoid unnecessary repetition, the present invention will not separately describe various possible combination methods.

[0151] Furthermore, any combination can be made among various different embodiments of the present invention, as long as it does not violate the idea of the present invention, and it should also be regarded as the content disclosed by the present invention.

Claims

1. An electrochemical method for the nitration of N-substituted anilines using sodium nitrite as the nitro source, characterized in that, It includes the following steps: using N-substituted aniline compounds as starting materials, sodium nitrite as a nitrating reagent, mixing with a solvent, setting positive and negative electrodes, and reacting under the conditions of energization and room temperature. After the reaction is completed, the nitration product of the N-substituted aniline compound is obtained through purification treatment; wherein the positive and negative electrode materials are each independently one of noble metals, transition metals, and carbon materials; wherein the general formula of the N-substituted aniline compound is: In the formula: R1 and R2 are each independently selected from the following groups: hydrogen, C1-C3 alkyl, and aryl; and R3 is selected from the following groups: hydrogen, C1-C4 alkyl, C1-C4 alkoxy, carbonyl functional group, halogen, and aryl.

2. The method according to claim 1, wherein The N-substituted aniline compound is any one of the following compounds:

3. The method according to claim 1, wherein The molar ratio of the N-substituted aniline compound to sodium nitrite is 1:(1.0 - 3.0).

4. The method according to claim 3, characterized in that, The positive and negative electrodes are specifically one of Pt(+) / Pt(-), Pt(+) / C(-), Pt(+) / Ni(-), C(+) / Pt(-), and Fe(+) / Pt(-).

5. The method according to claim 4, wherein The energization current is 5 - 20 mA.

6. The method according to claim 5, wherein The solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, toluene, N-methylpyrrolidone, N,N-dimethylacetamide, and 1,4-dioxane, used alone or in mixture with water.

7. The method according to claim 1, characterized in that, The concentration of the N-substituted aniline compound in the solvent is 0.06 - 0.12 mol / L.

8. The method according to any one of claims 1-7, characterized in that, The reaction time is 5 - 8 hours.

9. The method according to any one of claims 1-7, characterized in that, The purification treatment includes: washing with sodium thiosulfate solution, extraction with ethyl acetate, washing with brine, drying with anhydrous sodium sulfate, concentration under reduced pressure, and column chromatography.

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