A process for the preparation of 3-phenylpyridine from pyridine N-oxide

Abstract

The application discloses a method for preparing 3-phenylpyridine compounds, NaH is suspended in anhydrous DMA and stirred, pyridine N-oxide and o-diiodobenzene are added dropwise, and the reaction is stirred at 40 DEG C to obtain rearrangement product 3-arylpyridine. Pyridine N-oxide is an important pyridine derivative, which is easily obtained by single-step oxidation of a pyridine parent body and can be used as a starting material to synthesize pyridine derivatives. In the application, pyridine N-oxide and o-diiodobenzene are used as raw materials to prepare 3-phenylpyridine under the action of NaH. All the raw materials are cheap and easy to obtain, the reaction is simple and reliable, and the operation is simple, so the application is a new method for preparing 3-phenylpyridine. The method does not need transition metal catalysis, the reagent is cheap and easy to obtain, the operation is simple, and the substrate range is wide. The method for preparing 3-phenylpyridine products has application value in drug synthesis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a method for preparing 3-phenylpyridine by reacting pyridine N-oxide with o-diiodobenzene. BACKGROUND

[0002] Pyridine ring is one of the most important heterocyclic structures, and exists in a large number of natural products, drugs and materials. According to statistics, pyridine has become the second most common nitrogen heterocycle in the drugs approved by the US Food and Drug Administration in recent years. Representative drugs containing pyridine ring include anti-tuberculosis drug isoniazid, proton pump inhibitor omeprazole, non-nucleoside reverse transcriptase inhibitor nevirapine, CYP17 inhibitor abiraterone acetate, antiallergic drug loratadine, second-generation non-receptor tyrosine protein kinase inhibitor nilotinib, blood coagulation factor X (FXa) blocker idursabane, calcitonin gene-related peptide-1 type receptor antagonist ramucirumab, small molecule CGRP receptor antagonist ubrogepant, and potassium ion competitive acid blocker vonoprazan, etc. In addition, compounds containing pyridine heterocycle also have a wide range of applications in the fields of pesticides, plastics, optoelectronic devices, catalysts, etc.

[0003]

[0004]

[0005] Therefore, developing new methods for pyridine functionalization is one of the important research directions in the field of organic synthesis. The aromatic nucleophilic substitution at the 2- and 4-positions of pyridine is easier to occur, and there are a large number of literature reports; while the 3-position functionalization is more challenging, and there are fewer literature reports. Existing technologies, the 3-position functionalization of pyridine includes transition metal-catalyzed coupling reaction, pyridine temporary de-aromatization-functionalization-re-aromatization, etc. For example, Itami et al. reported that pyridine reacted with aryl triflate under the catalysis of Pd(OAc)2, and finally obtained the product of CH arylization at the 3-position of pyridine.

[0006]

[0007] In 2022, Wang et al. used borane to catalyze the temporary de-aromatization of pyridine, and realized the meta-alkylation, trifluoromethylthiolation and difluoromethylthiolation of pyridine in sequence through the sequence of borohydration, substitution and oxidative aromatization.

[0008] In particular, the prior art preparation of 3- (2-hydroxy) phenyl pyridine compounds is limited, most of which are achieved by using palladium-catalyzed Suzuki reaction, which can introduce a variety of functional groups on the pyridine meta position, but such reactions require the use of complex ligands and expensive palladium metal. For example: 3-bromopyridine and 2-hydroxybenzoic acid as raw materials, under the catalysis of dicyclohexyl (2', 6'-dimethoxy-[1, 1'-biphenyl]-2-yl) phosphine and palladium, 3- (2-hydroxy) phenyl pyridine compound is generated.

[0009]

[0010] In summary, transition metal catalysis is currently widely used for functionalization at the 3-position of pyridine, but metal-catalyzed reactions often have problems such as harsh reaction conditions, high cost, heavy metal and ligand residues; and most transition metal-free pyridine functionalization reactions require complex operation steps. Therefore, it is necessary to develop a new type of pyridine functionalization method that is simple, mild and effective. SUMMARY

[0011] The application discloses a method for preparing 3-phenyl pyridine compounds from o-diiodobenzene and pyridine N-oxide, which is simple in operation, low in raw material cost, mild in reaction condition and easy to mass-produce without transition metal catalysis. The method is to generate 3-phenyl pyridine compounds through the insertion rearrangement reaction of sodium hydride (60% NaH mineral oil dispersion) on o-diiodobenzene and pyridine N-oxide. The application solves the problems of traditional methods for preparing such products, such as complicated operation, high reagent cost and long preparation period.

[0012] The application adopts the following technical scheme:

[0013] A method for preparing 3-phenyl pyridine from pyridine N-oxide, comprising the following steps: in the presence of sodium hydride, o-diiodobenzene and pyridine N-oxide are used as raw materials to react and prepare 3-phenyl pyridine.

[0014] The application discloses a method for preparing 3-phenyl pyridine from o-diiodobenzene and pyridine N-oxide, which is simple in operation, low in raw material cost, mild in reaction condition and easy to mass-produce without transition metal catalysis. The method is to generate 3-phenyl pyridine compounds through the insertion rearrangement reaction of sodium hydride (60% NaH mineral oil dispersion) on o-diiodobenzene and pyridine N-oxide. The application solves the problems of traditional methods for preparing such products, such as complicated operation, high reagent cost and long preparation period.

[0015] In the application, the molar ratio of pyridine N-oxide, o-diiodobenzene and sodium hydride is 1: (1-3): (2-6), and the molar ratio is preferably 1:2:5.

[0016] In the application, the reaction temperature is 10-60 ℃, and the reaction time is 5-20 hours; preferably, the reaction temperature is 40 ℃, and the reaction time is 12 hours.

[0017] In the present application, the reaction is carried out in a solvent, which is tetrahydrofuran (THF), dimethylacetamide (DMA) or 1,4-dioxane, preferably DMA.

[0018] In the present application, the chemical structure of o-diiodobenzene is as follows:

[0019]

[0020] The chemical structure of pyridine N-oxide is as follows:

[0021]

[0022] The structure of the product 3-phenylpyridine compound is as follows:

[0023]

[0024] In the above structure, R 1 may be hydrogen, methoxy, dioxanyl, methyl, tert-butyl, phenyl, etc.; R 2 is hydrogen, various straight-chain alkanes, branched alkanes, cycloalkanes, aryl groups, alkenyl groups, such as methyl, ethyl, propyl, benzyl, cyclopentyl, cyclohexyl, phenyl, ethenyl, etc.

[0025] In the previous research, 2-(trimethylsilyl) trifluoromethanesulfonate phenyl ester is used to prepare 3-phenylpyridine compounds, which is complicated and needs to use butyllithium and low-temperature conditions, and is not economical and practical in large-scale preparation. In the present application, sodium hydride is used as an activator to activate o-diiodobenzene and pyridine N-oxide to obtain various 3-phenylpyridine compounds. The method of the present application is carried out under mild reaction conditions and is simple to operate, and the raw materials are cheap and easy to obtain, without any transition metal catalysis or strict anhydrous conditions, and is more popular. DETAILED DESCRIPTION

[0026] In the present application, o-diiodobenzene and pyridine N-oxide are used as raw materials, and 3-phenylpyridine compounds are obtained in the presence of sodium hydride (60% NaH mineral oil dispersion). The specific method is as follows: NaH is weighed in a reaction bottle, anhydrous DMA is added, and then pyridine N-oxide and o-diiodobenzene DMA solution are added in sequence under stirring, and 3-phenylpyridine compounds are obtained by reaction at 40°C. Compounds containing pyridine heterocyclic rings have a wide range of applications in the fields of drugs, pesticides, plastics, optoelectronic devices, catalysts, etc., and the product of the present application contains hydroxyl and pyridyl groups, can be amplified, and has good application prospect in the synthesis of new materials, such as curing agent and curing accelerator of high-performance resin materials.

[0027] ​​To better understand the technical content of this invention, the following embodiments are provided for detailed explanation. All raw materials are commercially available products or prepared according to literature methods, and the specific operations and testing methods are conventional techniques. (NMR spectrum) 1 HNMR and 13 All C NMR measurements were performed using an Agilent 400 MHz and a Bruker 400 MHz instrument. The sample solvent was CDCl3 or DMSO. d 6 The NMR data report includes: chemical shift, peak area integral, coupling constant, peak shape, etc. The TLC plates were manufactured by Yantai Huanghai Chemical Plant, providing visualization at wavelengths of 254 nm and 365 nm. The silica gel used for rapid column chromatography had a mesh size of 200-300 mesh. The reaction was carried out in air, and the product was separated using conventional purification methods after the reaction. All reagents used were commercially available analytical grade or chemically pure, and were used directly unless otherwise specified. Anhydrous solvents were all redistilled solvents or commercially available drying solvents (such as Bailingwei). Example 1

[0028] Weigh NaH (60% in oil, 100 mg, 2.5 mmol, 5.0 equiv) into a reaction flask, add 2 mL of anhydrous DMA, stir at room temperature for 5 min, then add pyridine nitrogen oxide 1 (47.5 mg, 0.5 mmol, 1.0 equiv, dissolved in 2 mL DMA) and o-diiodobenzene 2a (329 mg, 1.0 mmol, 2.0 equiv, dissolved in 1 mL DMA) dropwise. React at 40 °C for 12 hours (TLC monitoring completion using a 254 nm UV lamp). Quench the reaction with saturated NH4Cl solution at 0 °C. Extract three times with ethyl acetate and back-extract three times with water. Finally, combine the organic phases, wash with saturated NaCl solution, dry with anhydrous Na2SO4, filter, add silica gel powder to the filtrate, concentrate under reduced pressure, and separate by rapid column chromatography (petroleum ether: ethyl acetate = ... The crude product was obtained by mixing 10:1, and then purified by DCM to obtain high-purity product 3; the reaction results under different operating conditions are shown in Table 1.

[0029] Table 1 Results under different reaction conditions

[0030]

[0031]

[0032] Transition metal catalysis is a widely used method for functionalization at the 3-position of pyridine, but metal catalysis reaction often has problems such as harsh reaction conditions, high cost, heavy metal and ligand residues, etc. For example, the prior art generates 3-(2-hydroxy)phenylpyridine under the catalysis of dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl) phosphine and palladium. The present application adopts a new technical idea, does not need transition metal or metal catalysis, uses simple and cheap sodium hydride, and uses conventional o-diiodobenzene and pyridine N-oxide as raw materials to obtain 3-phenylpyridine compounds, overcoming the technical prejudice that such reactions all need metal catalysts according to the prior art, and solving the problems of harsh reaction conditions, high cost, heavy metal and ligand residues, etc. existing in the prior art.

[0033] The above product data is characterized as follows:

[0034] 2-(pyridin-3-yl)phenol (3): White solid, 41.9 mg, 49% yield. Mp. 168-170 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.73 (s, 1H), 8.73 (d, J = 2.3 Hz, 1H),8.49 (dd, J = 4.8, 1.7 Hz, 1H), 7.94 (dt, J = 8.0, 2.0 Hz, 1H), 7.42 (dd, J =7.9, 4.8 Hz, 1H), 7.31 (dd, J = 7.6, 1.7 Hz, 1H), 7.22 (td, J = 7.7, 1.8 Hz,1H), 6.98 (dd, J = 8.2, 1.2 Hz, 1H), 6.91 (td, J = 7.4, 1.2 Hz, 1H). 13 C NMR(101 MHz, DMSO- d 6 ): δ 154.57, 149.56, 147.47, 136.34, 134.19, 130.30, 129.36,124.38, 123.12, 119.66, 116.11. HRMS (ESI): calculated for [C11 H 10 NO (M+H)] + : 172.0757, found: 172.0764. Example 2

[0035] NaH (60% in oil, 5.0 equiv) was weighed into a reaction flask, 2 mL of anhydrous DMA was added, and stirred at room temperature for 5 min. Substituted pyridine N-oxide 1a-1n (0.5 mmol, 1.0 equiv, dissolved in 2 mL of DMA) and o-diiodobenzene 2a (2.0 equiv, dissolved in 1 mL of DMA) were added dropwise in sequence, and the reaction was carried out at 40 °C for 12 h. After the reaction was completed, saturated NH4Cl solution was added at 0 °C to quench the reaction, and the reaction liquid was transferred to a separatory funnel, extracted with ethyl acetate 3 times, and the aqueous phase was back-extracted 2 times. Finally, the organic phases were combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate. The product (3a-3n) was separated by flash column chromatography (petroleum ether: ethyl acetate = 400:1). The different reaction substrates (substituted pyridine N-oxide 1a-1n and o-diiodobenzene 2a) and the corresponding 3-phenylpyridine derivatives 3a-3n obtained are shown in Table 2. The substituents of substituted pyridine N-oxide 1a-1n are the same as those of 3-phenylpyridine derivatives 3a-3n.

[0036] Table 2 Reaction of substituted pyridine N-oxides with o-diiodobenzene

[0037]

[0038] The above product data are characterized as follows:

[0039] 2-(6-ethylpyridin-3-yl)phenol (3a): White solid, 55.7 mg, 56% yield. Mp. 164-166 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.70 (s, 1H), 8.70 – 8.60 (m,1H), 7.85 (dd, J = 8.0, 2.4 Hz, 1H), 7.30 – 7.26 (m, 2H), 7.19 (td, J = 7.7,1.7 Hz, 1H), 6.98 (dd, J = 8.1, 1.2 Hz, 1H), 6.89 (td,J = 7.4, 1.2 Hz, 1H),2.77 (q, J = 7.6 Hz, 2H), 1.26 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 160.67, 154.57, 148.78, 136.72, 131.47, 130.16, 129.02, 124.54,121.23, 119.61, 116.05, 30.30, 13.80. HRMS (ESI): calculated for [C 13 H 14 NO (M+H)] + : 200.1070, found: 200.1073.

[0040] 2-(6-propylpyridin-3-yl)phenol (3b):White solid, 54.3 mg, 51% yield.Mp. 138-140 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.68 (s, 1H), 8.63 (dd, J = 2.4,0.8 Hz, 1H), 7.84 (dd, J = 8.0, 2.4 Hz, 1H), 7.29 (dd, J = 7.6, 1.7 Hz, 1H),7.26 (dd, J = 8.0, 0.9 Hz, 1H), 7.21 – 7.17 (m, 1H), 6.96 (dd, J = 8.1, 1.2Hz, 1H), 6.89 (td, J = 7.4, 1.2 Hz, 1H), 2.76 – 2.67 (m, 2H), 1.77 – 1.66 (m,2H), 0.93 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, DMSO- d 6): δ 159.44, 154.54,148.81, 136.57, 131.42, 130.17, 129.04, 124.50, 121.89, 119.62, 116.04,39.24, 22.44, 13.80. HRMS (ESI): calculated for [C 14 H 16 NO (M+H)] + : 214.1226,found: 214.1229.

[0041] 2-(6-vinylpyridin-3-yl)phenol (3c):White solid, 22.7 mg, 23% yield.Mp. 171-172 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.76 (s, 1H), 8.72 (d, J = 2.2Hz, 1H), 7.94 (dd, J = 8.1, 2.3 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.33 (dd, J = 7.6, 1.7 Hz, 1H), 7.21 (td, J = 7.7, 1.7 Hz, 1H), 6.97 (dd, J = 8.2, 1.2Hz, 1H), 6.91 (td, J = 7.4, 1.2 Hz, 1H), 6.84 (dd, J = 17.5, 10.8 Hz, 1H),6.25 (dd, J = 17.5, 1.7 Hz, 1H), 5.47 (dd, J = 10.8, 1.7 Hz, 1H). 13 C NMR (101MHz, DMSO- d 6): δ 154.62, 152.90, 149.31, 136.85, 136.73, 133.08, 130.13,129.34, 124.17, 120.77, 119.68, 117.80, 116.11. HRMS (ESI): calculated for [C 13 H 12 NO (M+H)] + : 198.0913, found: 198.0921.

[0042] 2-(6-phenylpyridin-3-yl)phenol (3d):White solid, 42.0 mg, 34% yield.Mp. 180-182 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.81 (s, 1H), 8.86 (d, J = 2.2Hz, 1H), 8.14 – 8.11 (m, 2H), 8.06 (dd, J = 8.3, 2.3 Hz, 1H), 7.99 (d, J =8.3 Hz, 1H), 7.51 (dd, J = 8.3, 6.5 Hz, 2H), 7.46 – 7.42 (m, 1H), 7.39 (dd, J = 7.6, 1.8 Hz, 1H), 7.23 (td, J = 7.7, 1.7 Hz, 1H), 7.01 (dd, J = 8.1, 1.2Hz, 1H), 6.93 (td, J = 7.5, 1.2 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.69,153.87, 149.42, 138.53, 137.30, 132.84, 130.13, 129.36, 128.91, 128.78,126.39, 124.07, 119.71, 119.42, 116.15. HRMS (ESI): calculated for [C17 H 14 NO(M+H)] + : 248.1070, found: 248.1064.

[0043] 2-(6-(trifluoromethyl)pyridin-3-yl)phenol (3e):White solid, 21.5 mg,18% yield. Mp. 156-158 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.99 (s, 1H), 8.94 (d, J = 2.1 Hz, 1H), 8.24 (dd, J = 8.1, 2.2 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H),7.41 (dd, J = 7.6, 1.7 Hz, 1H), 7.28 (td, J = 7.7, 1.7 Hz, 1H), 7.02 (dd, J =8.1, 1.2 Hz, 1H), 6.95 (td, J = 7.5, 1.2 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6 ):δ 154.77, 150.04, 144.24 (q, J = 33.33 Hz), 138.14, 137.64, 130.48, 130.35,122.85, 121.91 (q, J = 274.72 Hz), 120.19 (q, J = 3.03 Hz), 119.85, 116.26. 19 F NMR (377 MHz, CDCl3): δ -61.47. HRMS (ESI): calculated for [C 12 H9F3NO (M+H)] + : 240.0631, found: 240.0627.

[0044] 2-(6-phenoxypyridin-3-yl)phenol (3f):White solid, 43.4 mg, 33% yield.Mp. 109-111 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.72 (s, 1H), 8.31 (d, J = 2.4Hz, 1H), 8.03 (dd, J = 8.5, 2.5 Hz, 1H), 7.46 – 7.40 (m, 2H), 7.29 (dd, J =7.6, 1.7 Hz, 1H), 7.24 – 7.15 (m, 4H), 7.05 (d, J = 8.5 Hz, 1H), 6.97 (dd, J = 8.1, 1.2 Hz, 1H), 6.89 (td, J = 7.4, 1.2 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 161.72, 154.47, 154.07, 146.98, 140.66, 130.05, 129.73, 129.58,129.03, 124.49, 123.87, 121.22, 119.62, 116.04, 110.58. HRMS (ESI):calculated for [C 17 H 14 NO2 (M+H)] + : 264.1019, found: 264.1029.

[0045] 2-(4-phenylpyridin-3-yl)phenol (3g):White solid, 58.0 mg, 47% yield.Mp. 198-200 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.38 (s, 1H), 8.57 (d, J = 5.0Hz, 1H), 8.47 (d, J= 0.7 Hz, 1H), 7.41 (dd, J = 5.1, 0.7 Hz, 1H), 7.27 –7.19 (m, 5H), 7.11 (ddd, J = 8.1, 7.3, 1.8 Hz, 1H), 6.93 (dd, J = 7.5, 1.7Hz, 1H), 6.80 (dd, J = 8.1, 1.2 Hz, 1H), 6.72 (td, J = 7.4, 1.1 Hz, 1H). 13 CNMR (101 MHz, DMSO- d 6 ): δ 154.72, 151.31, 148.36, 147.83, 138.97, 132.80,131.36, 129.06, 128.41, 128.08, 127.69, 124.66, 124.04, 118.91, 115.44. HRMS(ESI): calculated for [C 17 H 14 NO (M+H)] + : 248.1070, found: 248.1071.

[0046] 2-(4-( tert -butyl)pyridin-3-yl)phenol (3h):White solid, 40.9 mg, 36%yield. Mp. 232-234 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.45 (s, 1H), 8.41 (d, J =5.4 Hz, 1H), 8.01 (s, 1H), 7.44 (d, J = 5.4 Hz, 1H), 7.21 (ddd, J = 8.1, 7.3,1.8 Hz, 1H), 7.04 (dd, J = 7.5, 1.8 Hz, 1H), 6.90 (dd, J = 8.2, 1.2 Hz, 1H),6.83 (td, J= 7.4, 1.2 Hz, 1H), 1.15 (s, 9H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 156.51, 154.99, 152.13, 148.20, 133.72, 131.63, 129.03, 127.87, 121.52,118.18, 115.31, 36.12, 30.79. HRMS (ESI): calculated for [C 15 H 18 NO (M+H)] + : 228.1383, found: 228.1387.

[0047] 2-(4,6-dimethylpyridin-3-yl)phenol (3i):White solid, 50.7 mg, 51%yield. Mp. 175-177 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.50 (s, 1H), 8.11 (s,1H), 7.21 (td, J = 7.7, 1.8 Hz, 1H), 7.13 (s, 1H), 7.05 (dd, J = 7.5, 1.8 Hz,1H), 6.93 (dd, J = 8.1, 1.2 Hz, 1H), 6.87 (td, J = 7.4, 1.2 Hz, 1H), 2.44 (s,3H), 2.10 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 156.02, 154.79, 149.04,145.48, 132.02, 130.88, 129.01, 124.68, 123.72, 119.04, 115.48, 23.53, 19.09.HRMS (ESI): calculated for [C 13 H 14 NO (M+H)] + : 200.1070, found: 200.1066.

[0048] 2-(2,4,6-trimethylpyridin-3-yl)phenol (3j):White solid, 71.4 mg, 67%yield. Mp. 165-167 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.33 (s, 1H), 7.19 (td, J = 7.6, 1.8 Hz, 1H), 6.96 – 6.93 (m, 3H), 6.86 (t, J = 7.4 Hz, 1H), 2.39 (s,3H), 2.11 (s, 3H), 1.93 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.97, 154.94,154.31, 145.48, 130.55, 130.42, 128.69, 125.10, 121.56, 119.22, 115.64,23.56, 22.84, 19.46. HRMS (ESI): calculated for [C 14 H 16 NO (M+H)] + : 214.1226,found: 214.1234.

[0049] 2-(5,6-dimethylpyridin-3-yl)phenol (3k):White solid, 61.7 mg, 62%yield. Mp. 155-157 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.62 (s, 1H), 8.41 (d, J =2.2 Hz, 1H), 7.66 (d, J = 2.2 Hz, 1H), 7.26 (dd, J = 7.6, 1.7 Hz, 1H), 7.18(td, J= 7.7, 1.8 Hz, 1H), 6.96 – 6.94 (m, 1H), 6.88 (td, J = 7.5, 1.2 Hz,1H), 2.43 (s, 3H), 2.28 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.52, 146.01,137.18, 131.72, 130.17, 130.14, 128.90, 124.59, 119.52, 115.99, 21.96, 18.66.HRMS (ESI): calculated for [C 13 H 14 NO (M+H)] + : 200.1070, found: 200.1074.

[0050] 2-(6,7-dihydro-5 H -cyclopenta[b]pyridin-3-yl)phenol (3l):Brown solid,72.8 mg, 69% yield. Mp. 173-175 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.64 (s, 1H),8.41 (d, J = 2.1 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.25 (dd, J = 7.6, 1.7Hz, 1H), 7.18 (td, J = 7.7, 1.8 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.88 (t, J = 7.4 Hz, 1H), 2.94 – 2.89 (m, 4H), 2.08 (p, J = 7.5 Hz, 2H). 13 C NMR (101MHz, DMSO- d 6): δ 163.08, 154.55, 147.34, 135.72, 132.39, 131.69, 130.26,128.86, 125.05, 119.51, 116.00, 33.28, 30.07, 22.95. HRMS (ESI): calculated for [C 14 H 14 NO (M+H)] + : 212.1070, found: 212.1067.

[0051] 2-(5,6,7,8-tetrahydroquinolin-3-yl)phenol (3m):White solid, 56.3 mg,50% yield. Mp. 210-212 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.65 (s, 1H), 8.45 (d, J = 2.2 Hz, 1H), 7.58 (d, J = 2.2 Hz, 1H), 7.26 (dd, J = 7.6, 1.8 Hz, 1H),7.18 (td, J = 7.7, 1.7 Hz, 1H), 6.97 – 6.95 (m, 1H), 6.88 (td, J = 7.4, 1.2Hz, 1H), 2.83 – 2.74 (m, 4H), 1.86 – 1.72 (m, 4H). 13 C NMR (101 MHz, DMSO- d 6 ):δ 154.65, 154.57, 146.56, 136.72, 131.45, 130.87, 130.17, 128.93, 124.67,119.56, 116.02, 31.78, 28.12, 22.78, 22.37. HRMS (ESI): calculated for[C 15 H 16 NO (M+H)] + : 226.1226, found: 226.1230.

[0052] 2-(3,5-dimethylpyridin-2-yl)phenol (3n):White solid, 47.8 mg, 48%yield. Mp. 102-103 ℃. 1 H NMR (400 MHz, CDCl3): δ 8.24 – 8.23 (m, 1H), 7.53(dd, J = 7.9, 1.7 Hz, 1H), 7.49 (d, J = 2.2 Hz, 1H), 7.29 – 7.25 (m, 1H),7.07 (dd, J = 8.2, 1.3 Hz, 1H), 6.90 (td, J = 7.6, 1.3 Hz, 1H), 2.52 (s, 3H),2.34 (s, 3H). 13 C NMR (101 MHz, CDCl3): δ 157.77, 153.61, 144.58, 141.89,131.46, 131.12, 130.09, 129.56, 121.72, 118.32, 117.87, 21.61, 17.94. HRMS(ESI): calculated for [C 13 H 14 NO (M+H)] + : 200.1070, found: 200.1078.

[0053] In addition to pyridine N-oxides, other heterocyclic N-oxides were explored for reaction with o-diiodobenzene, as in Example Three. Example Three

[0054]

[0055] NaH (60% in oil, 5.0 equiv) was weighed into a reaction flask, 2 mL of anhydrous DMA was added and stirred at room temperature for 5 min. The heterocyclic nitroxide 1o (0.5 mmol, 1.0 equiv, dissolved in 2 mL of DMA) and o-diiodobenzene 2a (2.0 equiv, dissolved in 1 mL of DMA) were added dropwise successively and the reaction was stirred at 40 °C for 12 h. After the reaction was completed, the reaction solution was transferred to a separatory funnel and extracted with ethyl acetate three times, and the aqueous phase was back-extracted twice with ethyl acetate. Finally, the organic phase was combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate. The product 3o was isolated by flash column chromatography (petroleum ether: ethyl acetate = 400: 1). The product was characterized as follows:

[0056] 2-(2,2-dimethyl-3,4-dihydro-2 H -pyrrol-5-yl)phenol (3o): Yellow oil,53.9 mg, 57% yield. Mp. 78-80 ℃. 1 H NMR (400 MHz, CDCl3): δ 14.01 (s, 1H),7.37 (dd, J = 7.8, 1.7 Hz, 1H), 7.32 (ddd, J = 8.8, 7.3, 1.7 Hz, 1H), 7.01(dd, J = 8.2, 1.2 Hz, 1H), 6.86 (td, J = 7.5, 1.2 Hz, 1H), 3.12 – 3.09 (m,2H), 1.88 – 1.84 (m, 2H), 1.37 (s, 6H). 13 C NMR (101 MHz, CDCl3): δ 173.38,161.31, 132.28, 129.15, 118.16, 117.20, 117.18, 72.85, 35.14, 34.76, 29.12.HRMS (ESI): calculated for [C 12 H 16 NO (M+H)] + : 190.1226, found: 190.1222. Example Four

[0057] NaH (60% in oil, 5.0 equiv) was weighed into a reaction flask and stirred at room temperature for 5 min. Substituted pyridine N-oxide 1, 1b or 1p (0.5 mmol, 1.0 equiv, dissolved in 2 mL DMA) and substituted o-diiodobenzene 2b-2i (2.0 equiv, dissolved in 1 mL DMA) were added sequentially dropwise and the reaction was stirred at 40 °C for 12 h. After the reaction was completed, the reaction was quenched with saturated NH4Cl solution at 0 °C and transferred to a separatory funnel. The aqueous phase was extracted with ethyl acetate twice and the organic phase was combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and the filtrate was added to silica gel powder and separated by flash column chromatography (petroleum ether: ethyl acetate = 400: 1) to give the corresponding product (3p-3y). The different reaction substrates (substituted pyridine N-oxides 1, 1b, 1p and o-diiodobenzene 2b-2i) and the obtained 3-phenylpyridine derivatives 3p-3y are shown in Table 3. (Note: 1p refers to 2,6-dimethylpyridine N-oxide).

[0058] Table 3. Reaction of substituted pyridine N-oxides with o-diiodobenzene

[0059]

[0060] The above product data are characterized as follows:

[0061] 2,3,4,5-tetramethyl-6-(pyridin-3-yl)phenol (3p): White solid, 38.6 mg, 34% yield. Mp. 212-214 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 8.50 (dd, J = 4.8, 1.8Hz, 1H), 8.32 (d, J = 2.2 Hz, 1H), 7.63 (s, 1H), 7.53 (dt, J = 7.7, 2.0 Hz,1H), 7.42 (dd, J = 7.7, 4.8 Hz, 1H), 2.18 (s, 3H), 2.13 (s, 3H), 2.12 (s,3H), 1.87 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6): δ 150.88, 149.50, 147.38,137.97, 135.04, 134.80, 131.43, 125.98, 124.59, 123.16, 121.15, 17.66, 16.40,15.90, 12.99. HRMS (ESI): calculated for [C 15 H 18 NO (M+H)] + : 228.1383, found:228.1387.

[0062] 2-(2,6-dimethylpyridin-3-yl)-4,5-dimethylphenol (3q):White solid,73.8 mg, 65% yield. Mp. 203-205 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.10 (s, 1H),7.33 (d, J = 7.7 Hz, 1H), 7.04 (d, J = 7.7 Hz, 1H), 6.78 (s, 1H), 6.72 (s,1H), 2.44 (s, 3H), 2.27 (s, 3H), 2.17 (s, 3H), 2.12 (s, 3H). 13 C NMR (101 MHz,DMSO- d 6 ): δ 155.43, 155.14, 152.08, 137.87, 136.44, 131.49, 130.74, 126.24,123.85, 119.92, 116.75, 23.66, 22.68, 19.28, 18.31. HRMS (ESI): calculatedfor [C 15 H 18 NO (M+H)] + : 228.1383, found: 228.1389.

[0063] 7-(2,6-dimethylpyridin-3-yl)-2,3-dihydrobenzo[ b][1,4]dioxin-6-ol (3r): White solid, 96.4 mg, 75% yield. Mp. 230-232 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.06 (s, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.03 (d, J = 7.7 Hz, 1H), 6.53(s, 1H), 6.43 (s, 1H), 4.23 – 4.21 (m, 2H), 4.18 – 4.15 (m, 2H), 2.43 (s,3H), 2.27 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 155.58, 155.25, 148.39,143.03, 138.03, 135.97, 130.17, 119.95, 119.60, 118.21, 103.78, 64.34, 63.78,23.66, 22.69. HRMS (ESI): calculated for [C 15 H 16 NO3 (M+H)] + : 258.1125, found:258.1134.

[0064] 6-(2,6-dimethylpyridin-3-yl)benzo[ d ][1,3]dioxol-5-ol (3s):Whitesolid, 74.1 mg, 61% yield. Mp. 238-240 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.19(s, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.04 (d, J = 7.7 Hz, 1H), 6.61 (s, 1H),6.54 (s, 1H), 5.95 (s, 2H), 2.43 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, DMSO- d 6 ): δ 155.66, 155.26, 149.07, 147.11, 139.84, 138.19, 130.56, 120.02,118.04, 109.77, 100.86, 97.77, 23.68, 22.67. HRMS (ESI): calculated for [C 14 H 14 NO3 (M+H)] + : 244.0968, found: 244.0974.

[0065] 2-(2,6-dimethylpyridin-3-yl)-4,5-dimethoxyphenol (3t):White solid,73.8 mg, 57% yield. Mp. 189-191 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.04 (s, 1H),7.37 (d, J = 7.7 Hz, 1H), 7.05 (d, J = 7.7 Hz, 1H), 6.63 (s, 1H), 6.57 (s,1H), 3.74 (s, 3H), 3.67 (s, 3H), 2.43 (s, 3H), 2.28 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 155.65, 155.17, 149.07, 148.31, 141.66, 138.23, 130.57, 119.99,117.25, 115.00, 100.91, 56.32, 55.41, 23.71, 22.79. HRMS (ESI): calculated for [C 15 H 18 NO3 (M+H)] + : 260.1281, found: 260.1285.

[0066] 2-(2,6-dimethylpyridin-3-yl)-5-methylphenol and 2-(2,6-dimethylpyridin-3-yl)-4- methylphenol (3u):White solid, 75.6 mg, 71% yield.Mp. 155-157 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.34 (s, 0.7H), 9.21 (s, 0.3H),7.36 – 7.32 (m, 1H), 7.06 (dd, J = 7.7, 2.2 Hz, 1H), 6.99 (dd, J = 8.0, 4.0Hz, 0.3H), 6.91 (d, J = 7.5 Hz, 0.7H), 6.84 (d, J = 2.3 Hz, 0.3H), 6.81 (d, J = 8.2 Hz, 0.3H), 6.73 (d, J = 1.6 Hz, 0.7H), 6.67 (dd, J = 7.7, 1.6 Hz,0.7H), 2.44 (m, 3H), 2.26 – 2.22 (m, 6H). 13 C NMR (101 MHz, DMSO- d 6 ): δ155.41, 155.35, 155.31, 155.26, 154.16, 152.05, 138.17, 137.93, 137.80,131.04, 130.78, 130.66, 130.48, 129.16, 127.46, 126.42, 123.80, 119.99,119.85, 116.06, 115.37, 23.69, 22.67, 20.87, 20.05. HRMS (ESI): calculatedfor [C 16 H 14 NO (M+H)] + : 214.1226, found: 214.1230.

[0067] 4-(2,6-dimethylpyridin-3-yl)-[1,1'-biphenyl]-3-ol and 3-(2,6-dimethylpyridin-3-yl) -[1,1'-biphenyl]-4-ol (3v):White solid, 66.0 mg, 48%yield. Mp. 182-184 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.68 (s, 1H), 7.62 (tt, J = 6.9, 1.3 Hz, 2H), 7.52 (dd, J = 8.4, 2.4 Hz, 0.36H), 7.48 (t, J = 7.8 Hz,1.64H), 7.43 – 7.35 (m, 2H), 7.34 (d, J = 1.8 Hz, 0.64H), 7.18 – 7.13 (m, 1H), 7.11 (dd, J = 7.7,1.6 Hz, 1H), 7.02 (d, J = 8.4 Hz, 0.36H), 2.47 (s, 3H), 2.31 (s, 3H). 13 C NMR(101 MHz, DMSO- d 6 ): δ 155.62, 155.59, 155.38, 155.35, 154.78, 154.18, 140.94,140.01, 139.93, 138.03, 137.93, 131.31, 131.14, 130.53, 130.29, 128.99,128.93, 128.83, 127.51, 127.14, 127.10, 126.53, 126.10, 125.94, 120.08,117.62, 116.06, 113.66, 23.73, 22.76. HRMS (ESI): calculated for [C 19 H 18 NO (M+H)] + : 276.1383, found: 276.1378.

[0068] 5-( tert -butyl)-2-(6-propylpyridin-3-yl)phenol (3w):White solid, 53.8mg, 40% yield. Mp. 199-202 ℃. 1 H NMR (400 MHz, DMSO- d 6 ): δ 9.52 (s, 1H), 8.62(dd, J = 2.4, 0.8 Hz, 1H), 7.83 (dd, J = 8.0, 2.3 Hz, 1H), 7.23 (t, J = 8.1Hz, 2H), 6.99 (d, J = 1.9 Hz, 1H), 6.92 (dd, J = 8.0, 1.9 Hz, 1H), 2.71 (dd, J = 8.4, 6.8 Hz, 2H), 1.76 – 1.67 (m, 2H), 1.27 (s, 9H), 0.93 (t, J = 7.4 Hz,3H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 159.16, 154.16, 151.88, 148.74, 136.40,131.38, 129.68, 121.86, 121.55, 116.68, 113.01, 39.24, 34.20, 31.06, 22.44,13.81. HRMS (ESI): calculated for [C 18 H 24 NO (M+H)] + : 270.1852, found: 270.1850.

[0069] 5-( tert -butyl)-2-(2,6-dimethylpyridin-3-yl)phenol (3x):White solid,88.0 mg, 69% yield. Mp. 180-183 ℃.1 H NMR (400 MHz, DMSO- d 6 ): δ 9.32 (s, 1H),7.35 (d, J = 7.7 Hz, 1H), 7.05 (d, J = 7.7 Hz, 1H), 6.97 – 6.95 (m, 2H), 6.89(dd, J = 8.0, 1.8 Hz, 1H), 2.44 (s, 3H), 2.27 (s, 3H), 1.28 (s, 9H). 13 C NMR(101 MHz, DMSO- d 6 ): δ 155.42, 155.26, 153.94, 151.50, 137.97, 130.62, 130.29,123.70, 119.98, 116.08, 112.47, 34.20, 31.14, 23.70, 22.77. HRMS (ESI):calculated for [C 17 H 22 NO (M+H)] + : 256.1696, found: 256.1703.

[0070] 5-( tert -butyl)-2-(pyridin-3-yl)phenol and 4-( tert -butyl)-2-(pyridin-3-yl)phenol (3y ):White solid, 36.3 mg, 32% yield. Mp. 186-189 ℃. 1 H NMR(400 MHz, DMSO- d 6 ): δ 9.60 (s, 0.75H), 9.53 (s, 0.25H), 8.75 – 8.74 (m, 1H),8.49 – 8.46 (m, 1H), 7.93 (dt, J = 7.8, 2.0 Hz, 1H), 7.43 – 7.38 (m, 1H),7.27 – 7.22 (m, 1H), 7.01 (d, J= 2.0 Hz, 1H), 6.95 – 6.90 (m, 1H), 1.28 (s,9H). 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.18, 152.22, 152.19, 149.62, 149.47,147.32, 147.22, 141.74, 136.36, 136.14, 134.65, 134.12, 129.81, 126.90,126.08, 123.60, 123.08, 121.41, 116.74, 115.68, 113.05, 34.22, 33.74, 31.35,31.03. HRMS (ESI): calculated for [C 15 H 18 NO (M+H)] + : 228.1383, found: 228.1381. Example Five

[0071] To verify the practicability of the method, a scale-up reaction experiment was carried out. A gram-scale experiment was carried out using 2,3-dimethylpyridine N-oxide and o-diiodobenzene as raw materials, and it was found that, compared with a small amount of reaction, the scale-up experiment could still obtain the desired product 3k in a yield of more than medium.

[0072]

[0073] The reaction substrates in the embodiments of the application can be routinely purchased or prepared according to conventional methods. As an example, the preparation methods of some raw materials are as follows.

[0074]

[0075] MCPBA (1.5 g, 8.75 mmol, 1.75 equiv.) was suspended in DCM (20 mL) at 0 °C, the pyridine derivative (5 mmol, 1.0 equiv.) in DCM (20 mL) was added, and the reaction was allowed to proceed at room temperature for 12 h. After the reaction was completed, the reaction was quenched by adding saturated NaHSO3solution, and the reaction was transferred to a separatory funnel, extracted with DCM twice, washed with saturated NaHSO3solution and 2 M NaOH solution twice, and washed with saturated NaCl solution twice. The organic phase was then combined, dried over anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate. The mixture was concentrated under reduced pressure and separated by flash column chromatography (dichloromethane: anhydrous methanol = 20: 1) to obtain the pyridine derivative-N-oxide with a yield of 50-78%.

[0076]

[0077] 2a is commercially available, 2b-2f are synthesized according to Method 1, and 2g-2i are synthesized according to Method 2.

[0078] Synthesis Method 1:

[0079]

[0080] H5IO6 (1.8 g, 8.0 mmol, 0.4 equiv.) and I2 (455.4 mg, 1.8 mmol, 0.9 equiv.) were weighed into a two-necked reaction flask, protected by N2, and stirred at room temperature with the addition of methanol (20 mL). A solution of the benzene derivative (20 mmol, 1.0 equiv.) in methanol (10 mL) was added, and the reaction was allowed to proceed at 70 °C for 20 h. After the reaction was completed, the reaction was quenched by adding saturated NaHSO3solution, stirred and cooled, and filtered under reduced pressure. The filter cake was washed with methanol, and the solid was collected and dried in an oven. The substituted diiodobenzene product (2b-2f) was obtained with a yield of 55-80%.

[0081] Synthesis Method 2:

[0082]

[0083] To a solution of 2-iodoaniline (20 mmol, 1.0 equiv.) in MeCN:H2O (1:1, 0.5 M) at 0 °C was added dropwise HC1 (12 M, 6.0 equiv.). To the reaction was added dropwise a solution of NaNCte (1.7 g, 24 mmol, 1.2 equiv.) in water while maintaining the reaction temperature below 5 °C. After stirring for 20 min, a solution of KI (8.3 g, 50 mmol, 2.5 equiv.) in water was added and stirring was continued for 20 min. The temperature was raised to 85 °C and stirring was continued for 3 h. After the reaction was complete, the reaction was extracted with ethyl acetate three times and washed with water, saturated NaHC03solution, saturated Na2S203solution, and finally saturated NaCl solution. The organic phases were combined, dried over anhydrous Na2S04, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by flash column chromatography to give the corresponding substituted o-diiodoarene (2g-2i) in 71-93% yield.

[0084] 1,2-diiodo-4,5-dimethylbenzene (2c): White solid, 4.2 g, 58% yield. Mp. 86-93 ℃. 1 H NMR (400 MHz, CDCl3): δ 7.59 (s, 2H), 2.13 (s, 6H). 13 C NMR(101 MHz, CDCl3): δ 140.6, 138.62, 103.94, 19.07.

[0085] 6,7-diiodo-2,3-dihydrobenzo[b][1,4]dioxine (2d): White solid, 4.3 g,55% yield. Mp. 105-112 ℃. 1 H NMR (400 MHz, CDCl3): δ 7.32 (s, 2H), 4.21 (s,4H). 13 C NMR (101 MHz, CDCl3): δ 144.41, 127.47, 96.23, 64.30.

[0086] 5,6-diiodobenzo[ d ][1,3]dioxole (2e): White solid, 5.7 g, 76% yield.Mp. 90-96 ℃. 1H NMR (400 MHz, CDCl3): δ 7.29 (d, J = 1.2 Hz, 2H), 5.97 (d, J = 1.4 Hz, 2H). 13 C NMR (101 MHz, CDCl3): δ 148.94, 118.79, 102.23, 96.51.

[0087] 1,2-diiodo-4,5-dimethoxybenzene (2f): White solid, 6.2 g, yield 80%.Mp. 127-133 ℃. 1 H NMR (400 MHz, CDCl3): δ 7.21 (s, 2H), 3.81 (s, 6H). 13 C NMR(101 MHz, CDCl3): δ 149.63, 121.69, 96.15, 56.24.

[0088] 4-( tert -butyl)-1,2-diiodobenzene (2g):Colorless oil, 7.2 g, 93%yield. 1 H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 2.3 Hz, 1H), 7.76 (d, J = 8.3Hz, 1H), 7.06 (dd, J = 8.3, 2.3 Hz, 1H), 1.28 (s, 9H). 13 C NMR (101 MHz,CDCl3): δ 153.18, 139.06, 136.94, 126.98, 108.08, 104.01, 34.65, 31.14.

[0089] The application discloses a new method for synthesizing a phenylated derivative of a pyridine 3-position by activating o-diiodobenzene by NaH and then reacting with pyridine N-oxide. Compared with other traditional methods, the method does not need to use transition metal catalysis, has mild reaction conditions, simple operation, can successfully realize the amplification of a kilogram scale, has high atom economy, provides a new method for pyridine functionalization, and has wide application prospect.

Claims

1. A method for preparing a compound of formula I from nitrogen oxides, characterized in that, The process includes the following steps: reacting o-diiodobenzene with nitrogen oxides in a solvent in the presence of sodium hydride to obtain compound I; the solvent is dimethylacetamide, or a mixture of tetrahydrofuran and dimethylacetamide; the chemical structural formula of o-diiodobenzene is as follows: ； The chemical structural formula of nitrogen oxides is as follows: ； The structural formula of compound I is as follows: ； In the above structural formula, R1 is one or more of hydrogen, methoxy, dioxyl, methyl, tert-butyl, and phenyl; R2 is one or more of hydrogen, methyl, ethyl, propyl, benzyl, cyclopentyl, cyclohexyl, phenyl, and vinyl.

2. The method for preparing compound I from nitrogen oxides according to claim 1, characterized in that, The reaction temperature is 10–60 °C, and the reaction time is 5–20 hours.

3. The method for preparing compound I from nitrogen oxides according to claim 1, characterized in that, The molar ratio of nitrogen oxides, o-diiodobenzene, and sodium hydride is 1:(1-3):(2-6).

4. The method for preparing compound I from nitrogen oxides according to claim 1, characterized in that, The reaction takes place in the air.

5. The method for preparing compound I from nitrogen oxides according to claim 1, characterized in that, The reaction does not require metal catalysis.

6. A method for preparing a compound of formula II from nitrogen oxides, characterized in that, The process includes the following steps: reacting o-diiodobenzene with nitrogen oxides in a solvent in the presence of sodium hydride to obtain compound II; the solvent is dimethylacetamide, or a mixture of tetrahydrofuran and dimethylacetamide; the chemical structural formula of o-diiodobenzene is as follows: ； Among them, R 1 It is hydrogen; The chemical structural formula of nitrogen oxides is as follows: ； The structural formula of compound II is as follows: 。 7. The method for preparing compound II from nitrogen oxides according to claim 6, characterized in that, The reaction temperature is 10–60 °C, and the reaction time is 5–20 hours.

8. The method for preparing compound II from nitrogen oxides according to claim 6, characterized in that, The molar ratio of nitrogen oxides, o-diiodobenzene, and sodium hydride is 1:(1-3):(2-6).

9. The method for preparing compound II from nitrogen oxides according to claim 6, characterized in that, The reaction takes place in the air.

10. The method for preparing compound II from nitrogen oxides according to claim 6, characterized in that, The reaction does not require metal catalysis.

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