Method for preparing 3-phenylpyridine from pyridine nitrogen oxide

Abstract

The invention discloses a method for preparing a 3-phenylpyridine compound, which comprises the following steps: suspending NaH in anhydrous DMA (direct memory access), stirring, dropwise adding pyridine nitrogen oxide and o-diiodobenzene, and stirring to react at 40 DEG C to obtain a rearrangement product 3-arylpyridine; pyridine nitrogen oxide is an important pyridine derivative, is easily obtained from a pyridine matrix through single-step oxidation, and can be used as an initial raw material to synthesize the pyridine derivative. According to the method, pyridine nitrogen oxide and o-diiodobenzene are used as raw materials to react under NaH to prepare the 3-phenylpyridine, all the raw materials are cheap and easy to obtain, the reaction is simple and reliable, the operation is simple, and the method is a novel method for preparing the 3-phenylpyridine. The method does not need transition metal catalysis, reagents are cheap and easy to obtain, operation is simple, and the substrate range is wide; the method for preparing the 3-phenylpyridine product has application value in medicine synthesis.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for preparing 3-phenylpyridine by reacting pyridine nitrogen oxide with o-diiodobenzene. Background Art

[0002] The 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 heterocyclic ring in drugs approved by the US Food and Drug Administration in recent years. Representative drugs containing pyridine rings include the anti-tuberculosis drug isoniazid, the proton pump inhibitor omeprazole, the non-nucleoside reverse transcriptase inhibitor nevirapine, the CYP17 inhibitor abiraterone acetate, the antiallergic drug loratadine, the second-generation non-receptor tyrosine protein kinase inhibitor nilotinib, the coagulation factor X (FXa) blocker edoxaban, the calcitonin gene-related peptide-1 receptor antagonist remgipam, the small molecule CGRP receptor antagonist ubagepam and the potassium ion competitive acid blocker vonoprazan. In addition, compounds containing pyridine heterocyclic rings are also widely used in pesticides, plastics, optoelectronic devices, catalysts and other fields.

[0003]

[0004]

[0005] Therefore, developing new methods for the functionalization of pyridine is one of the important research directions in the field of organic synthesis. Aromatic nucleophilic substitution at the 2- and 4-positions of pyridine is more likely 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 include methods for the functionalization of the 3-position of pyridine, including transition metal-catalyzed coupling reactions, temporary dearomatization of pyridine-functionalization-rearomatization, etc. For example, Itami et al. reported the reaction of pyridine with trifluoromethanesulfonic acid aryl esters under the catalysis of Pd(OAc)2, and finally obtained the product of CH arylation at the 3-position of pyridine.

[0006]

[0007] In 2022, Wang et al. used borane to catalyze the temporary dearomatization of pyridine. Through the sequence of hydroboration, substitution, and oxidative aromatization, they successively achieved meta-alkylation, trifluoromethylthiolation, and difluoromethylthiolation of pyridine.

[0008] In particular, the existing methods for preparing 3-(2-hydroxy)phenylpyridine compounds are relatively limited, and most of them are achieved by using the Suzuki reaction catalyzed by palladium. Although this method can introduce a variety of functional groups at the meta-position of pyridine, this type of reaction requires the use of complex ligands and expensive metal palladium. For example: 3-bromopyridine and 2-hydroxyphenylboronic acid are used as raw materials, and 3-(2-hydroxy)phenylpyridine compounds are generated under the catalysis of dicyclohexyl (2',6'-dimethoxy-[1,1'-biphenyl]-2-yl) phosphine and palladium.

[0009]

[0010] In summary, transition metal catalysis is currently the most widely used method for functionalization at the 3-position of pyridine, but metal catalysis often has problems such as harsh reaction conditions, high cost, heavy metal and ligand residues; and most pyridine functionalization reactions without transition metal catalysis require cumbersome operation steps. Therefore, it is very necessary to develop a new pyridine functionalization method that is simple to operate, mild and effective. Summary of the invention

[0011] The invention discloses a method for preparing 3-phenylpyridine compounds by using o-diiodobenzene and pyridine nitrogen oxide. The method is simple to operate, has cheap and readily available raw materials, mild reaction conditions, does not require transition metal catalysis, and is easy to prepare on a large scale. The method is to use sodium hydride (60% NaH mineral oil dispersion) to act on o-diiodobenzene and pyridine nitrogen oxide to perform insertion rearrangement reaction to generate 3-phenylpyridine compounds. The invention solves the problems of complicated operation, high reagent price, and long preparation cycle in the preparation of such products using traditional methods.

[0012] The present invention adopts the following technical solution: A method for preparing 3-phenylpyridine from pyridine nitrogen oxide comprises the following steps: in the presence of sodium hydride, taking o-diiodobenzene and pyridine nitrogen oxide as raw materials, reacting to prepare 3-phenylpyridine.

[0013] The invention discloses a method for preparing 3-phenylpyridine by reacting o-diiodobenzene with pyridine nitrogen oxide. Specifically, in the presence of sodium hydride, o-diiodobenzene and pyridine nitrogen oxide are reacted in a solvent to obtain a 3-(2-hydroxy)arylpyridine compound.

[0014] In the present invention, the molar ratio of pyridine nitrogen oxide, o-diiodobenzene and sodium hydride is 1:(1-3):(2-6), preferably 1:2:5.

[0015] In the present invention, the reaction temperature is 10-60°C and the reaction time is 5-20 hours; preferably, the reaction temperature is 40°C and the reaction time is 12 hours.

[0016] In the present invention, the reaction is carried out in a solvent, and the solvent is tetrahydrofuran (THF), dimethylacetamide (DMA) or 1,4-dioxane, preferably DMA.

[0017] In the present invention, the chemical structural formula of o-diiodobenzene is as follows:

[0018] The chemical structure of pyridine nitrogen oxide is as follows: ,

[0019] The structural formula of the product 3-phenylpyridine compound is as follows: ,

[0020] In the above structural formula, R 1 It can be hydrogen, methoxy, dioxanyl, methyl, tert-butyl, phenyl, etc.; R 2 It is hydrogen, various straight-chain alkanes, branched-chain alkanes, cycloalkanes, aryl groups, alkenyl groups, such as methyl, ethyl, propyl, benzyl, cyclopentyl, cyclohexyl, phenyl, vinyl, etc.

[0021] In previous studies, 2-(trimethylsilyl)phenyl trifluoromethanesulfonate was used to prepare 3-phenylpyridine compounds, which is complicated to prepare, requires butyl lithium and low temperature conditions, and is not economical and practical when prepared in large quantities. The present invention uses sodium hydride as an activator to activate o-diiodobenzene and pyridine nitrogen oxide to react to obtain a variety of 3-phenylpyridine compounds. The method of the present invention is carried out under mild reaction conditions, is simple to operate, has cheap and easy-to-obtain raw materials, does not require any transition metal catalysis or strict anhydrous conditions, and is more popular. DETAILED DESCRIPTION

[0022] The present invention uses o-diiodobenzene and pyridine nitrogen oxide as raw materials, and reacts in the presence of sodium hydride (60% NaH mineral oil dispersion) to obtain 3-phenylpyridine compounds. The specific method is to weigh NaH in a reaction bottle, add anhydrous DMA, and then add pyridine nitrogen oxide and o-diiodobenzene DMA solution in sequence under stirring, and react at 40°C to obtain 3-phenylpyridine compounds. Compounds containing pyridine heterocycles are widely used in the fields of medicine, pesticides, plastics, optoelectronic devices, catalysts, etc., and the product of the present invention contains hydroxyl and pyridine groups, which can amplify the reaction and have good application prospects in the synthesis of new materials, such as as a curing agent and curing accelerator for high-performance resin materials.

[0023] In order to more clearly understand the technical content of the present invention, the following examples are given in detail. All raw materials are commercially available products or prepared according to literature methods, and the specific operations and testing methods are conventional techniques. 1 HNMR and 13 C NMR was measured using Agilent 400 MHz and Bruker 400 MHz instruments, and 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 thin layer chromatography plate is produced by Yantai Huanghai Chemical Plant, and visual monitoring is performed at wavelengths of 254 nm and 365 nm. The silica gel mesh used for rapid column chromatography is 200-300 mesh. The reaction is carried out in the air, and the product is separated by conventional purification methods after the reaction. All reagents used are commercially available analytical grade or chemically pure. Unless otherwise specified, they are used directly. Anhydrous solvents are all redistilled solvents or commercially available dry solvents (B&K). Embodiment 1

[0024] NaH (60% in oil, 100 mg, 2.5 mmol, 5.0 equiv) was weighed into a reaction bottle, and 2 mL of anhydrous DMA was added. After stirring at room temperature for 5 min, 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) were added dropwise in sequence. The reaction was allowed to proceed at 40 °C for 12 h (TLC monitoring of the reaction was performed using a 254 nm UV detector lamp). Saturated NH4Cl solution was then added to quench the reaction at 0 °C, and the reaction was extracted three times with ethyl acetate and back-extracted with aqueous solution three times. The organic phases were combined and washed with saturated NaCl solution, dried with anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate, concentrated under reduced pressure, and separated by rapid column chromatography (petroleum ether: ethyl acetate = 10:1), a crude product was obtained, and then purified by DCM beating to obtain a high-purity product 3; the reaction results under different operating conditions are shown in Table 1.

[0025] Table 1 Results under different reaction conditions

[0026]

[0027] Functionalization at the 3-position of pyridine is currently widely used with transition metal catalysis, but metal catalytic reactions often have problems such as harsh reaction conditions, high costs, heavy metals and ligand residues. 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 invention adopts a new technical idea, does not require transition metals or metal catalysis, uses simple, easy-to-obtain and cheap sodium hydride, and uses conventional o-diiodobenzene and pyridine nitrogen oxide as raw materials to react to obtain 3-phenylpyridine compounds, which overcomes the technical prejudice of the prior art that such reactions require the participation of metal catalysts, and also solves the problems of harsh reaction conditions, high costs, heavy metals and ligand residues in the prior art.

[0028] The above product data are characterized as follows: 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 [C 11 H10 NO (M+H)] + : 172.0757, found: 172.0764. Embodiment 2

[0029] Weigh NaH (60% in oil, 5.0 equiv) into the reaction bottle, add 2 mL of anhydrous DMA, and stir at room temperature for 5 min. Substituted pyridine nitrogen oxides 1a-1n (0.5 mmol, 1.0 equiv, dissolved in 2 mL DMA) and o-diiodobenzene 2a (2.0 equiv, dissolved in 1 mL DMA) were then added dropwise, and the reaction was carried out at 40°C for 12 h. After the reaction was completed, saturated NH4Cl solution was added to quench the reaction at 0°C. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate for 3 times and aqueous phase for 2 times. Finally, the organic phases were combined, washed with saturated NaCl solution, dried with anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate to mix the sample. The corresponding products (3a-3n) were separated by rapid column chromatography (petroleum ether: ethyl acetate = 400:1). The corresponding products (3a-3n) were obtained. The corresponding products of different reaction substrates (substituted pyridine nitrogen oxides 1a-1n and o-diiodobenzene 2a) and the obtained 3-phenylpyridine derivatives 3a-3n are shown in Table 2. The substituents of the substituted pyridine nitrogen oxides 1a-1n are the same as those of the 3-phenylpyridine derivatives 3a-3n.

[0030] Table 2 Reaction of substituted pyridine nitrogen oxides with o-diiodobenzene

[0031] The above product data are characterized as follows: 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. 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. 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. 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 [C 17 H14 NO(M+H)] + : 248.1070, found: 248.1064. 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. 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. 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. 2-(4-( tart -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 ): δ156.51, 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. 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. 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. 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. 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): calculatedfor [C 14 H 14 NO (M+H)] + : 212.1070, found: 212.1067. 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. 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. In addition to pyridine nitrogen oxide, the present invention explores the reaction of other heterocyclic nitrogen oxides with o-diiodobenzene, such as Example 3. Embodiment 3

[0032]

[0033] Weigh NaH (60% in oil, 5.0 equiv) into the reaction bottle, add 2 mL of anhydrous DMA, and stir at room temperature for 5 min. Then, add heterocyclic nitrogen oxide 1o (0.5 mmol, 1.0 equiv, dissolved in 2 mL DMA) and o-diiodobenzene 2a (2.0 equiv, dissolved in 1 mL DMA) dropwise, react at 40 °C for 12 h, and after the reaction, add saturated NH4Cl solution to quench at 0 °C. Transfer the reaction solution to a separatory funnel, extract with ethyl acetate 3 times, and back-extract with water 2 times. Finally, combine the organic phases, wash with saturated NaCl solution, add anhydrous Na2SO4 to dry, filter, add silica gel powder to the filtrate, and separate by rapid column chromatography (petroleum ether: ethyl acetate = 400:1) to obtain the corresponding product 3o. The product data are as follows: 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. Embodiment 4

[0034] Weigh NaH (60% in oil, 5.0 equiv) into the reaction bottle, add 2 mL of anhydrous DMA and stir at room temperature for 5 min. Then, substituted pyridine nitrogen 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 dropwise, 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 solution. The reaction solution was transferred to a separatory funnel, extracted with ethyl acetate three times, and aqueous back-extracted twice. Finally, the organic phases were combined, washed with saturated NaCl solution, dried with anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate to mix the sample. The corresponding products (3p-3y) were separated by rapid column chromatography (petroleum ether: ethyl acetate = 400:1). The corresponding reaction substrates (substituted pyridine nitrogen oxide 1, 1b, 1p and o-diiodo aromatic hydrocarbons 2b-2i) and the obtained 3-phenylpyridine derivatives 3p-3y are shown in Table 3. (Note: 1p refers to 2,6-dimethylpyridine nitrogen oxide).

[0035] Table 3 Reaction of substituted pyridine nitrogen oxides with o-diiodinated aromatic hydrocarbons

[0036] The above product data are characterized as follows: 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. 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. 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. 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). 13 C 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. 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): calculatedfor [C 15 H 18 NO3 (M+H)] + : 260.1281, found: 260.1285. 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. 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 = 2.4 Hz, 0.36H), 7.30 – 7.26 (m,0.36H), 7.19 (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. 5-( tart -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. 5-( tart -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. 5-( tart -butyl)-2-(pyridin-3-yl)phenol and 4-( tart -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). 13C 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. Embodiment 5

[0037] In order to verify the practicality of the method, a scaled-up reaction experiment was conducted. Using 2,3-dimethylpyridine nitrogen oxide and o-diiodobenzene as raw materials, a gram-scale experiment was conducted, and it was found that compared with a small-scale reaction, the scaled-up experiment could still obtain the desired product 3k with a medium or higher yield.

[0038]

[0039] In the embodiments of the present invention, each reaction substrate can be purchased from the market or prepared according to conventional methods. As an example, the preparation method of some raw materials is as follows.

[0040]

[0041] m-Chloroperbenzoic acid (1.5 g, 8.75 mmol, 1.75 equiv.) was suspended in DCM (20 mL) at 0 °C, and a solution of pyridine derivative (5 mmol, 1.0 equiv.) in DCM (20 mL) was added, and the mixture was reacted at room temperature for 12 h. After the reaction was completed, a saturated NaHSO3 solution was added to quench the mixture, and the reaction solution was transferred to a separatory funnel, extracted twice with DCM, and then washed twice with a saturated NaHSO3 solution and a 2M NaOH solution, and then the organic phase was washed twice with a saturated NaCl solution. Finally, the organic phases were combined, dried over anhydrous Na2SO4, filtered, and silica gel powder was added to the filtrate to mix the sample, and the mixture was concentrated under reduced pressure. The pyridine derivative-N-oxide was separated by flash column chromatography (dichloromethane: anhydrous methanol = 20:1) with a yield of 50-78%.

[0042]

[0043] 2a is commercially available, 2b-2f are synthesized according to method 1, and 2g-2i are synthesized according to method 2.

[0044] Synthesis method 1:

[0045] H5IO6 (1.8 g, 8.0 mmol, 0.4 equiv.) and I2 (455.4 mg, 1.8 mmol, 0.9 equiv.) were weighed and placed in a two-necked reaction flask. Under N2 protection, methanol (20 mL) was added and stirred at room temperature. Then, a methanol solution (10 mL) of benzene (20 mmol, 1.0 equiv.) was added and refluxed at 70 °C for 20 h. After the reaction was completed, a saturated solution of NaHSO3 was added to quench the reaction. The mixture was 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 to obtain substituted diiodobenzene products (2b-2f) with a yield of 55-80%.

[0046] Synthesis method 2:

[0047] At 0°C, add HCl (12 M, 6.0 equiv.) to a solution of 2-iodoarylamine (20 mmol, 1.0 equiv.) in MeCN:H2O (1:1, 0.5 M). Keep the reaction temperature below 5°C and add an aqueous solution of NaNO2 (1.7 g, 24 mmol, 1.2 equiv.) to the reaction solution. Stir for 20 min and then add an aqueous solution of KI (8.3 g, 50 mmol, 2.5 equiv.) and continue stirring for 20 min. Raise the temperature to 85°C and stir for 3 h. After the reaction was completed, the mixture was extracted with ethyl acetate three times, washed with water, saturated NaHCO3 solution, saturated Na2S2O3 solution and finally with saturated NaCl solution. The organic phases were combined, dried by adding anhydrous Na2SO4 and filtered. Silica gel powder was added to the filtrate and the sample was mixed. The mixture was concentrated under reduced pressure and separated by rapid column chromatography to obtain the corresponding substituted o-diiodoaromatic hydrocarbons (2g-2i) with a yield of 71-93%.

[0048] 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). 13C NMR(101 MHz, CDCl3): δ 140.6, 138.62, 103.94, 19.07. 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. 5,6-diiodobenzo[ d ][1,3]dioxole (2e): White solid, 5.7 g, 76% yield.Mp. 90-96 ℃. 1 H 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. 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. 4-( tart -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. The present invention discloses a novel method for synthesizing pyridine 3-phenyl derivatives by activating o-diiodobenzene with NaH and then reacting with pyridine nitrogen oxide. Compared with other traditional methods, the method of the present invention does not require the use of transition metal catalysis, has mild reaction conditions, is simple to operate, can successfully achieve gram-scale amplification, has high atom economy, provides a new method for pyridine functionalization, and has broad application prospects.

Claims

1. A method for preparing 3-phenylpyridine from pyridine nitrogen oxide, comprising the following steps: in the presence of sodium hydride, taking o-diiodobenzene and pyridine nitrogen oxide as raw materials, reacting to prepare 3-phenylpyridine.

2. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 1, characterized in that: In the presence of sodium hydride, o-diiodobenzene is reacted with pyridine nitrogen oxide in a solvent to obtain a 3-(2-hydroxy)arylpyridine compound.

3. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 2, characterized in that: The solvent is one or more of tetrahydrofuran, dimethylacetamide or 1,4-dioxane.

4. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 1, characterized in that: The reaction temperature is 10 to 60°C and the reaction time is 5 to 20 hours.

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

6. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 1, characterized in that: The chemical structure of o-diiodobenzene is as follows: ; The chemical structure of pyridine nitrogen oxide is as follows: 、 ; The structural formula of the product 3-phenylpyridine is as follows: 、 ; In the above structural formula, R 1 is one or more of hydrogen, methoxy, dioxanyl, methyl, tert-butyl, and phenyl; R 2 It is one or more of hydrogen, straight-chain alkane, branched-chain alkane, cycloalkane, aryl and alkenyl.

7. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 1, characterized in that: The reaction is carried out in air.

8. The method for preparing 3-phenylpyridine from pyridine nitrogen oxide according to claim 1, characterized in that: The reaction does not require transition metals or metal catalysts.

9. The application of o-diiodobenzene and pyridine nitrogen oxide as raw materials in the reaction preparation of 3-phenylpyridine.

10. 3-phenylpyridine prepared according to the method of claim 1.

Images