A method of photo-initiated nitro-reduction hydrogenation

Abstract

The application discloses a method for photo-induced nitro reduction hydrogenation, and belongs to the field of medical compound synthesis.The method provided by the application takes iron trichloride and palladium-carbon as the catalysts of main reactions, and realizes nitro reduction into amino under the conditions of normal temperature, normal pressure and nitrogen, the reaction has high catalytic efficiency and fast reaction rate, the reaction time is only 10 minutes, the yield of the product obtained by nitro reduction is high, the experimental cost is greatly reduced, the method is suitable for the synthesis and amplification of later-stage compounds, the method has simple steps, wide substrate application range, and the effects of high efficiency, green environmental protection, safety and cost saving, and the reaction has fast reaction rate, and has excellent application prospect in industrial production.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical compound synthesis technology, and in particular to a method for photo-initiated nitro reduction hydrogenation. Background Technology

[0002] Aniline is an important chemical raw material, playing an irreplaceable role in the large-scale industrial preparation of raw materials in fine chemicals, pharmaceuticals, and pesticides. The amino group (-NH2) in the aniline molecule is the key functional group, making it a crucial chemical intermediate widely used in dyes, pharmaceuticals, pesticides, surfactants, textile auxiliaries, chelating agents, and polymer materials. Currently, the hydrogenation of nitro compounds mainly relies on heterogeneous catalysts, using hydrogen as the hydrogen source, and reacting under high temperature and pressure. These include noble metal catalysts such as palladium, platinum, and ruthenium, as well as inexpensive metal catalysts such as iron, cobalt, nickel, and copper. However, using heterogeneous catalysts for the hydrogenation reduction of nitro compounds can damage other functional groups, resulting in poor selectivity. Furthermore, the storage and transportation of hydrogen, its flammability and explosiveness, and the high temperature and pressure required for the reaction pose significant risks.

[0003] To synthesize functionalized aniline compounds in a more environmentally friendly, safe, and efficient manner, metal-free catalytic nitro reduction methods have been developed, using reducing agents such as hydrazine hydrate and sodium borohydride. While replacing gaseous H2 with more reactive hydrogenating agents (such as NaSH, formate, and hydrazine) can avoid the harsh reaction conditions that retain unsaturated groups, the irreversible consumption of reagents leads to substantial waste and increases the burden of waste treatment. Therefore, developing new green, safe, and environmentally friendly conversion methods has become an urgent priority.

[0004] In recent years, photocatalytic reduction has received widespread attention due to its advantages such as safety, environmental friendliness, simple operation, high reactivity, and wide applicability. Patent CN120423960A discloses a method for photo-initiated ferric chloride-catalyzed reduction of nitro groups to amino groups and its applications. However, this reaction has a low reaction rate, making industrialization difficult. Therefore, there is an urgent need for a faster photocatalytic reaction to achieve nitro reduction. Summary of the Invention

[0005] To overcome the above shortcomings, the present invention aims to provide a method for nitro reduction hydrogenation, so as to solve the problem that the photocatalytic nitro reduction hydrogenation reaction is time-consuming and difficult to industrialize.

[0006] To achieve the above objectives, the technical solution provided by the present invention is as follows: This invention provides a method for photo-initiated nitro reductive hydrogenation, comprising the following steps: Under nitrogen atmosphere and normal temperature and pressure, the compound shown in formula (1) was dissolved in tetrahydrofuran solvent, and a photocatalytic system composed of iron-based catalyst and palladium-based catalyst was added. Water was used as the hydrogen source, and the reaction was carried out under light irradiation to obtain the reduction product shown in formula (2). The reaction formula is:

[0007] Wherein, when X1 and X2 = C, a benzene ring is formed, and R1, R2, R3, R4, and R5 are each independently selected from one or more of cyano, ester, carbonyl, halogen, carboxyl, boron ester, and phenylacetyl groups; When X1=N and X2=C, a pyridine ring is formed, and R1, R3, and R4 are each independently selected from one or more halogens and alkyl groups; When X1 and X2 = N, a pyrimidine ring is formed, and R1, R3, and R5 are each independently selected from one or more of halogen, alkyl, ester, methoxy, and methylamino groups.

[0008] Furthermore, the iron-based catalyst is ferric chloride.

[0009] Furthermore, the palladium-based catalyst is palladium on carbon.

[0010] Furthermore, the wavelength of the illumination is 245-525nm.

[0011] Furthermore, the wavelength of the light is 395nm.

[0012] Furthermore, the reaction time is 5-15 minutes.

[0013] Furthermore, the reaction time is 10 minutes.

[0014] Furthermore, the molar ratio of the compound shown in formula (1) to ferric chloride is 5:2.

[0015] Furthermore, the mass ratio of the compound shown in formula (1) to palladium on carbon is 100:5.

[0016] By adopting the above technical solution, the beneficial technical effects obtained by the present invention are as follows: The method of this invention is green, environmentally friendly, and safe, with no hydrogen or toxic reagents involved. The method of the present invention is simple to operate, does not require the use of hydrogen gas in the reduction hydrogenation reaction, and the subsequent reduction hydrogenation reaction operation is simple and the method has low cost; The method of this invention is highly efficient. Under a nitrogen-containing atmosphere, the catalyst has high catalytic efficiency and high yield of reduced hydrogenation products. The reaction time is fast, requiring only ten minutes, and it has excellent prospects for industrial application. Attached Figure Description

[0017] Figure 1This is the reaction formula provided in the embodiments of the present invention; Figure 2 It is the product prepared in Example 1 of this invention. 1 H NMR spectrum; Figure 3 It is the product prepared in Example 1 of this invention. 13 C NMR spectrum; Figure 4 It is the product prepared in Example 2 of this invention. 1 H NMR spectrum; Figure 5 It is the product prepared in Example 2 of this invention. 13 C NMR spectrum; Figure 6 It is the product prepared in Example 3 of this invention. 1 H NMR spectrum; Figure 7 It is the product prepared in Example 3 of this invention. 13 C NMR spectrum; Figure 8 It is the product prepared in Example 4 of this invention. 1 H NMR spectrum; Figure 9 It is the product prepared in Example 4 of this invention. 13 C NMR spectrum; Figure 10 It is the product prepared in Example 5 of this invention. 1 H NMR spectrum; Figure 11 It is the product prepared in Example 5 of this invention. 13 C NMR spectrum; Figure 12 It is the product prepared in Example 6 of this invention. 1 H NMR spectrum; Figure 13 It is the product prepared in Example 6 of this invention. 13 C NMR spectrum; Figure 14 It is the product prepared in Example 7 of this invention. 1 H NMR spectrum; Figure 15 It is the product prepared in Example 7 of this invention. 13 C NMR spectrum; Figure 16 It is the product prepared in Example 8 of this invention. 1 H NMR spectrum; Figure 17 It is the product prepared in Example 8 of this invention. 13 C NMR spectrum. Detailed Implementation

[0018] The present invention is illustrated by the following examples.

[0019] Example 1

[0020] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (28.8 mg, 0.1777 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 47 mg of the reduced product (yield 83.0%).

[0021] 1 H NMR (400 MHz, Chloroform- d ) δ 7.06 – 6.95 (m, 2H), 6.53 – 6.46 (m,2H), 3.46 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 145.02, 129.14, 123.13, 116.27. Example 2

[0022]

[0023] Under a nitrogen atmosphere and at room temperature, 2,3,4,-trichloronitrobenzene (70 mg, 0.3091 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (20.1 mg, 0.1237 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (27.8 mg, 1.5455 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 54 mg of the reduced product (yield 88.9%).

[0024] 1 H NMR (400 MHz, Chloroform- d ) δ 7.05 (d, J = 8.8 Hz, 1H), 6.53 (d,J = 8.8 Hz, 1H), 4.11 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 143.11, 131.44, 128.27, 121.89,118.58, 113.85. Example 3

[0025]

[0026] Under a nitrogen atmosphere and at room temperature, pentachloronitrobenzene (70 mg, 0.2370 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (15.3 mg, 0.0948 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (21.3 mg, 1.185 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 62 mg of the reduced product (yield 98.6%).

[0027] 1 H NMR (400 MHz, DMSO- d 6) δ 6.26 (s, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ 142.98, 130.45, 117.32, 115.97. Example 4

[0028]

[0029] Under a nitrogen atmosphere and at room temperature, 4-bromonitrobenzene (70 mg, 0.3465 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (22.5 mg, 0.1386 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (31.2 mg, 1.733 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 52 mg of the reduced product (yield 87.2%).

[0030] 1 H NMR (400 MHz, Chloroform-d ) δ 7.17 – 7.13 (m, 2H), 6.51 – 6.45 (m,2H), 3.58 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 145.46, 132.03, 116.74, 110.20. Example 5

[0031]

[0032] Under a nitrogen atmosphere and at room temperature, 2,5-dibromonitrobenzene (70 mg, 0.2492 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (16.2 mg, 0.09968 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (22.4 mg, 1.246 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 52 mg of the reduced product (yield 83.2%).

[0033] 1 H NMR (400 MHz, Chloroform- d ) δ 7.15 (d, J = 8.5 Hz, 1H), 6.80 (d, J = 2.3 Hz, 1H), 6.64 (dd, J = 8.4, 2.3 Hz, 1H), 4.05 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 145.30, 133.64, 122.16, 121.76,118.13, 107.78. Example 6

[0034]

[0035] Under a nitrogen atmosphere and at room temperature, 4-chloro-3-nitrotrifluorotoluene (70 mg, 0.3104 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (20.1 mg, 0.1241 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (27.9 mg, 1.552 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 51 mg of the reduced product (yield 84.1%).

[0036] 1 H NMR (400 MHz, Chloroform- d ) δ 7.25 (d, J = 8.3 Hz, 1H), 6.95 –6.88 (m, 1H), 6.87 – 6.75 (m, 1H), 4.15 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 143.23, 130.26, 129.85, 125.18,122.47, 122.33, 115.36, 115.32, 115.28, 115.24, 112.21, 112.17, 112.13,112.09. 19 F NMR (376 MHz, Chloroform- d ) δ -62.80. Example 7

[0037]

[0038] Under a nitrogen atmosphere and at room temperature, 2-chloro-4-nitrobenzoic acid (70 mg, 0.3473 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (22.5 mg, 0.1389 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (31.3 mg, 1.737 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 58 mg of the reduced product (yield 97.3%).

[0039] 1H NMR (400 MHz, DMSO- d 6) δ 7.66 (d, J = 8.6 Hz, 1H), 6.63 (d, J = 2.1Hz, 1H), 6.53 – 6.48 (m, 1H), 6.07 (s, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ 166.64, 153.49, 135.18, 134.19, 115.83,114.99, 111.95. Example 8

[0040]

[0041] Under a nitrogen atmosphere and at room temperature, 4-nitrobenzene (70 mg, 0.4726 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (30.7 mg, 0.1890 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (42.5 mg, 2.363 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 49 mg of the reduced product (yield 87.8%).

[0042] 1 H NMR (400 MHz, Chloroform- d ) δ 7.34 – 7.31 (m, 2H), 6.59 – 6.55 (m, 2H), 4.15 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 150.55, 133.82, 120.26, 114.45,99.99. Example 9

[0043]

[0044] Under a nitrogen atmosphere and at room temperature, 4-nitroacetophenone (70 mg, 0.4239 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (27.5 mg, 0.1696 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (38.1 mg, 2.119 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 51 mg of the reduced product (yield 89.1%).

[0045] 1 H NMR (400 MHz, Chloroform- d ) δ 7.71 (d, J = 8.7 Hz, 2H), 6.55 (d, J = 8.7 Hz, 2H), 4.21 (s, 2H), 2.41 (s, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 196.69, 151.43, 130.84, 127.61,113.70, 26.12. Example 10

[0046]

[0047] Under a nitrogen atmosphere and at room temperature, ethyl 4-aminobenzoate (70 mg, 0.3587 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (23.3 mg, 0.1435 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (32.3 mg, 1.794 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 54 mg of the reduced product (yield 91.2%).

[0048] 1 H NMR (400 MHz, Chloroform- d ) δ 7.77 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 4.23 (q, J= 7.1 Hz, 2H), 4.04 (s, 2H), 1.27 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 166.82, 150.93, 131.56, 119.89,113.77, 60.35, 14.44. Example 11

[0049]

[0050] Under a nitrogen atmosphere and at room temperature, methyl p-nitrophenylacetate (70 mg, 0.3587 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (23.3 mg, 0.1435 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (32.3 mg, 1.794 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 37 mg of the reduced product (62.4% yield).

[0051] 1 H NMR (400 MHz, Chloroform- d ) δ 6.97 (d, J = 8.4 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 3.59 (s, 3H), 3.45 (s, 2H), 3.43 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 172.71, 145.47, 130.13, 123.82,115.30, 51.98, 40.37. Example 12

[0052]

[0053] Under a nitrogen atmosphere and at room temperature, methyl 2-nitro-4,5-dimethoxybenzoate (70 mg, 0.2902 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (18.8 mg, 0.1161 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (26.1 mg, 1.451 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 38 mg of the reduced product (62% yield).

[0054] 1 H NMR (400 MHz, Chloroform- d ) δ 7.21 (s, 1H), 6.06 (s, 1H), 5.53 (s,2H), 3.76 (s, 3H), 3.76 (s, 3H), 3.74 (s, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 168.17, 154.77, 147.17, 140.51,112.49, 101.92, 99.30, 56.33, 55.72, 51.31. Example 13

[0055]

[0056] Under a nitrogen atmosphere and at room temperature, methyl 2-nitro-4,5-dimethoxybenzoate (70 mg, 0.3080 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (20.0 mg, 0.1232 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (27.7 mg, 1.540 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 55 mg of the reduced product (yield 90.6%).

[0057] 1 H NMR (400 MHz, Chloroform- d) δ 7.66 – 7.62 (m, 4H), 7.47 – 7.43 (m,1H), 7.39 – 7.35 (m, 2H), 6.65 – 6.52 (m, 2H), 4.14 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 195.40, 151.10, 138.90, 132.98,131.44, 129.54, 128.11, 127.29, 113.64. Example 14

[0058]

[0059] Under a nitrogen atmosphere and at room temperature, methyl 2-nitro-4,5-dimethoxybenzoate (70 mg, 0.3080 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (20.0 mg, 0.1232 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (27.7 mg, 1.540 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 51 mg of the reduced product (yield 84%).

[0060] 1 H NMR (400 MHz, Chloroform- d ) δ 7.76 – 7.71 (m, 2H), 7.53 – 7.48 (m,1H), 7.42 – 7.37 (m, 2H), 7.20 – 7.16 (m, 1H), 7.08 – 7.03 (m, 2H), 6.84 –6.80 (m, 1H), 3.74 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 197.00, 146.50, 138.70, 137.79,132.31, 130.06, 129.09, 128.20, 120.69, 118.99, 115.92. Example 15

[0061]

[0062] Under a nitrogen atmosphere and at room temperature, 4-nitrophenylboronic acid pinacol ester (70 mg, 0.2810 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (18.23 mg, 0.1124 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (25.3 mg, 1.405 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 57 mg of the reduced product (yield 92.6%).

[0063] 1 H NMR (400 MHz, Chloroform- d ) δ 7.54 (d, J = 8.4 Hz, 2H), 6.58 (d, J = 8.4 Hz, 2H), 3.76 (s, 2H), 1.24 (s, 12H). 13 C NMR (101 MHz, Chloroform- d ) δ 149.34, 136.43, 114.09, 83.31,24.87. Example 16

[0064]

[0065] Under a nitrogen atmosphere and at room temperature, 2-chloro-5-nitropyridine (70 mg, 0.4415 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (28.6 mg, 0.1766 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (39.7 mg, 2.207 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 42 mg of the reduced product (yield 74.0%).

[0066] 1 H NMR (400 MHz, Chloroform- d ) δ 7.76 (d, J = 3.0 Hz, 1H), 7.00 (dd, J = 8.5, 0.5 Hz, 1H), 6.89 (dd,J = 8.5, 3.0 Hz, 1H), 3.70 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 141.82, 140.07, 136.30, 124.86,124.14. Example 17

[0067]

[0068] Under a nitrogen atmosphere and at room temperature, 2,6-dichloro-5-nitropyridine (70 mg, 0.3627 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (23.5 mg, 0.1451 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (32.6 mg, 1.813 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 49 mg of the reduced product (yield 83.1%).

[0069] 1 H NMR (400 MHz, Chloroform- d ) δ 7.01 – 6.98 (m, 1H), 6.98 – 6.95 (m,1H), 4.11 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 137.85, 136.39, 133.71, 124.12,122.63. Example 18

[0070]

[0071] Under a nitrogen atmosphere and at room temperature, 2-chloro-5-nitropyrimidine (70 mg, 0.4388 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (28.5 mg, 0.1755 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (39.5 mg, 2.194 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 47 mg of the reduced product (yield 82.4%).

[0072] 1 H NMR (400 MHz, DMSO- d 6) δ 8.03 (s, 2H), 5.75 (s, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ 146.48, 144.65, 142.79. Example 19

[0073]

[0074] Under a nitrogen atmosphere and at room temperature, 4,6-dichloro-5-nitropyrimidine (70 mg, 0.3610 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (23.4 mg, 0.1444 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (32.5 mg, 1.805 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 47 mg of the reduced product (93% yield).

[0075] 1 H NMR (400 MHz, Chloroform- d ) δ 8.13 (s, 1H), 4.50 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 145.95, 144.21, 135.95. Example 20

[0076]

[0077] Under a nitrogen atmosphere and at room temperature, 5-nitro-4,6-dimethoxypyrimidine (70 mg, 0.3781 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (24.5 mg, 0.1512 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (34.0 mg, 1.890 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 45 mg of the reduced product (76.7% yield).

[0078] 1 H NMR (400 MHz, Chloroform- d ) δ 7.89 (s, 1H), 3.92 (s, 6H), 3.49 (s, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 156.09, 143.91, 112.93, 52.95. Example 21

[0079]

[0080] Under a nitrogen atmosphere and at room temperature, 6-chloro-N-methyl-5-nitro-4-pyrimidinamine (70 mg, 0.3712 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (24.1 mg, 0.1485 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (33.4 mg, 1.856 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 40 mg of the reduced product (68.9% yield).

[0081] 1 H NMR (400 MHz, DMSO- d 6) δ 7.76 (s, 1H), 6.90 – 6.82 (m, 1H), 4.96 (s, 2H), 2.89 (d, J = 4.6 Hz, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 153.13, 146.31, 136.89, 124.03, 28.33. Example 22

[0082]

[0083] Under a nitrogen atmosphere and at room temperature, ethyl 2,6-dichloro-5-nitropyrimidine-4-carboxylate (70 mg, 0.2631 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (17.07 mg, 0.1052 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (23.6 mg, 1.316 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 57 mg of the reduced product (yield 91.9%).

[0084] 1 H NMR (400 MHz, Chloroform- d ) δ 6.17 (s, 2H), 4.41 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 165.38, 150.66, 144.44, 139.53,133.79, 62.78, 14.19. Example 23

[0085]

[0086] Under a nitrogen atmosphere and at room temperature, 2-methyl-4,6-dichloro-5-nitropyrimidine (70 mg, 0.3365 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (21.8 mg, 0.1346 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (30.3 mg, 1.683 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 56 mg of the reduced product (yield 93.4%).

[0087] 1 H NMR (400 MHz, Chloroform- d ) δ 4.30 (s, 2H), 2.50 (s, 3H). 13 C NMR (101 MHz, Chloroform- d) δ 156.01, 144.36, 132.99, 24.32. Compare with Example 1

[0088] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), tetrahydrofuran (8 mL), ferric sulfate (71.4 mg, 0.1777 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube, irradiated with 395 nm light, and stirred for 10 min. After the reaction was completed, gas chromatography-mass spectrometry (GC-MS) showed no product formation.

[0089] Compare with Example 2

[0090] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), tetrahydrofuran (8 mL), ferric nitrate (43.0 mg, 0.1777 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube, irradiated with 395 nm light, and stirred for 10 min. After the reaction was completed, gas chromatography-mass spectrometry (GC-MS) showed no product formation.

[0091] Compare with Example 3

[0092] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (28.8 mg, 0.1777 mmol, 0.4 eq), palladium acetate (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 31.9 mg of the reduced product (yield 56.3%).

[0093] Compare with Example 4

[0094] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), tetrahydrofuran (8 mL), ferric chloride (28.8 mg, 0.1777 mmol, 0.4 eq), palladium chloride (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was complete, the mixture was extracted with dichloromethane and aqueous solution. The organic layers were combined, dried over anhydrous sodium sulfate, and then purified by vacuum distillation and silica gel column chromatography to obtain 25.4 mg of the reduced product (yield 44.9%).

[0095] Compare with Example 5

[0096] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), acetonitrile (8 mL), ferric chloride (28.8 mg, 0.1777 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was completed, gas chromatography-mass spectrometry (GC-MS) showed no product formation.

[0097] Compare with Example 6

[0098] Under a nitrogen atmosphere and at room temperature, p-chloronitrobenzene (70 mg, 0.4443 mmol, 1 eq), N,N-dimethylformamide (8 mL), ferric chloride (28.8 mg, 0.1777 mmol, 0.4 eq), palladium on carbon (3.5 mg, 5%), and water (40 mg, 2.222 mmol, 5 eq) were added to a 15 mL quartz tube. The mixture was irradiated with 395 nm light and stirred for 10 min. After the reaction was completed, gas chromatography-mass spectrometry (GC-MS) showed no product formation.

[0099] As can be seen from the above embodiments, the preparation method provided by the present invention can prepare a high-yield reduction product simply by using a simple catalyst and light under a nitrogen atmosphere.

Claims

1. A method for photo-initiated nitro-reduction hydrogenation, characterized in that, Includes the following steps: Under a nitrogen atmosphere and at room temperature and pressure, the compound shown in formula (1) was dissolved in tetrahydrofuran solvent, and a photocatalytic system composed of an iron-based catalyst and a palladium-based catalyst was added. Water was used as the hydrogen source, and the reaction was carried out under light irradiation to obtain the reduction product shown in formula (2). The iron-based catalyst was ferric chloride. The reaction formula is: Wherein, when X1 and X2 = C, a benzene ring is formed, and R1, R2, R3, R4, and R5 are each independently selected from one or more of cyano, ester, carbonyl, halogen, carboxyl, and boron ester groups; When X1=N and X2=C, a pyridine ring is formed, and the compound shown in formula (1) is 2-chloro-5-nitropyridine or 2,6-dichloro-5-nitropyridine; When X1 and X2 = N, a pyrimidine ring is formed, and the compound shown in formula (1) is 2-chloro-5-nitropyrimidine, 4,6-dichloro-5-nitropyrimidine, 5-nitro-4,6-dimethoxypyrimidine, 6-chloro-N-methyl-5-nitro-4-pyrimidineamine, ethyl 2,6-dichloro-5-nitropyrimidine-4-carboxylate, and 2-methyl-4,6-dichloro-5-nitropyrimidine.

2. The method of claim 1, wherein, The palladium-based catalyst is palladium on carbon.

3. The method of claim 1, wherein, The wavelength of the light is 245-525nm.

4. The method of claim 3, wherein, The wavelength of the light is 395 nm.

5. The method of claim 1, wherein, The reaction time is 5-15 minutes.

6. The method of claim 5, wherein, The reaction time is 10 minutes.

7. The method of claim 1, wherein, The molar ratio of the compound shown in formula (1) to ferric chloride is 5:

2.

8. The method of claim 2, wherein, The mass ratio of the compound shown in formula (1) to palladium on carbon is 100:5.

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