Method for preparing phenol by hydroxylation of boronic acid derivatives in air without photocatalyst and alkali condition

Abstract

The present application relates to the technical field of organic synthesis, and more particularly to a method for preparing phenol by hydroxylation of boronic acid derivatives in air without light catalyst and base. The method comprises the following steps: under room temperature conditions, oxygen in air is used as an oxidant, and oxidation hydroxylation reaction of aryl boronic acid and ether solvent occurs under light, and after the reaction is completed, phenolic compounds are obtained by post-processing. In the preparation process, no transition metal is added as a catalyst, no light catalyst is added, no oxidant is added, no base is added, no heating is added, and phenolic compounds are prepared in high yield under light catalytic conditions.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and more particularly to a method for preparing phenol by air hydroxylation of boronic acid derivatives under the conditions of no photocatalyst and no base. BACKGROUND

[0002] Phenolic compounds are important organic chemical raw materials, which are widely used in the fields of medicine, organic synthesis and industry. In recent years, with the rapid development of industry, electronics and other industries, the demand for phenolic compounds has increased significantly. Therefore, researchers are constantly exploring more superior synthesis methods of phenolic compounds. The hydroxylation of aryl boronic acid is one of the most effective methods for synthesizing phenolic compounds. However, there are still some deficiencies in this method. For example, the pioneering research on the hydroxylation of aryl boronic acid focuses on the use of metal photocatalysts (ACS Sustainable Chem. Eng. 2020, 8, 2682-2687), and in some cases, strong bases are required (Green Chem., 2019, 21, 4614-4618), or in the absence of metal catalysts, stoichiometric strong oxidants are used (Org. Lett., 2012, 14, 3494-3497; Tetrahedron Lett., 2015, 56, 1524-1527), or the help of microwave reaction equipment is required (Green Chem., 2019, 21, 4614-4618).

[0003] In recent years, the research on the photocatalytic oxidation hydroxylation of aryl boronic acid to generate phenol has attracted widespread attention. However, in these photocatalytic reactions, photocatalysts are required, and most of the photocatalysts have problems such as complicated synthesis and high cost. Although patent CN110668921 A reports a method for preparing phenol by aerobic hydroxylation of boronic acid derivatives without photocatalyst, the method still requires the addition of an organic base, the reaction time is long (24 hours), and a UV light source is used.

[0004] Therefore, it is of great significance to develop a green, efficient, mild and simple oxidation method for synthesizing phenolic compounds. SUMMARY

[0005] In view of the above problems, the present application provides a method for preparing phenol by air hydroxylation of boronic acid derivatives under the conditions of no photocatalyst and no base. In the preparation process, no transition metal catalyst, no oxidant, no acid and base, no heating, and no photocatalytic conditions are required. The aryl boronic acid is efficiently oxidized in air to prepare phenolic compounds.

[0006] The application aims to provide a method for preparing phenol by hydroxylation of boronic acid derivatives in air without photocatalyst and alkali, comprising the following steps:

[0007] The aryl boronic acid and the ether solvent are subjected to oxidative hydroxylation under light at room temperature with oxygen in air as an oxidant, and the phenolic compound is obtained after reaction and post-processing.

[0008] Preferably, the reaction time is 5-60 min.

[0009] Preferably, the reaction time is 5 min.

[0010] Preferably, the ratio of aryl boronic acid to ether solvent is 1 mmol: 1-10 mL.

[0011] Preferably, the ratio of aryl boronic acid to ether solvent is 1 mmol: 3 mL.

[0012] Preferably, the light source for light irradiation is an ultraviolet lamp, a xenon lamp, an LED lamp or an incandescent lamp.

[0013] Preferably, the light source for light irradiation is a xenon lamp.

[0014] Preferably, the ether solvent is one or both of tetrahydrofuran and 2-methyl-tetrahydrofuran.

[0015] Preferably, the aryl boronic acid is one of phenyl boronic acid, o-methylphenyl boronic acid, m-methylphenyl boronic acid, p-methylphenyl boronic acid, 4-methoxyphenyl boronic acid, 2-fluorophenyl boronic acid, 4-fluorophenyl boronic acid, 4-chlorophenyl boronic acid, 2,4-dichlorophenyl boronic acid, 2-chloro-5-methylphenyl boronic acid, 2,6-di-tert-butyl-4-methylphenyl boronic acid, a-naphthyl boronic acid, β-naphthyl boronic acid, 4-aldehyde phenyl boronic acid, 2-formylamino phenyl boronic acid, 4-(benzyloxy carbonyl) phenyl boronic acid, m-trifluoromethyl phenyl boronic acid, p-nitrophenyl boronic acid and 4-methyl-3-nitrophenyl boronic acid.

[0016] Compared with the prior art, the application has the following beneficial effects:

[0017] The application discloses a new method for preparing phenolic compounds, which is characterized in that aryl boronic acid is subjected to oxidative hydroxylation under light at room temperature with O2 in air as an oxidant and tetrahydrofuran and / or 2-methyl-tetrahydrofuran as a solvent to generate phenolic compounds. The method does not need to add a photocatalyst or alkali, and the reaction can be completed quickly under a xenon lamp at room temperature for 5 minutes, and has the advantages of mild reaction conditions, simple operation, high safety, few side reactions and short reaction time. DETAILED DESCRIPTION

[0018] With reference to the embodiments of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by a person of ordinary skill in the art without creative effort belong to the scope of protection of the present application.

[0019] As shown in Table 1, the present application uses aryl boronic acid as a raw material, air as an oxidant in tetrahydrofuran or 2-methyltetrahydrofuran solvent, and the boronic acid group in aryl boronic acid is converted into hydroxyl under the irradiation of a light source. This method does not require heating, does not require the addition of a photocatalyst and a base, has the advantages of simple operation, greenness, high efficiency, less by-products, short reaction time, etc. The reaction conditions of the present application are shown in Table 1.

[0020]

[0021] Table 1 Reaction condition optimization a

[0022] Example Solvent Base addition Light source Yield (%) 1 Tetrahydrofuran None UV lamp 90 2 Tetrahydrofuran None Blue / green LED lamp 85 / 88 3 Tetrahydrofuran None Incandescent lamp 92 4 Tetrahydrofuran None Xenon lamp 98 5 b ]] Tetrahydrofuran None Xenon lamp 0 6 Tetrahydrofuran None Darkness 0 7c Tetrahydrofuran Triethylamine Xenon lamp 51 8 2-Methyltetrahydrofuran None Xenon lamp 91 9 N,N-Dimethylformamide None Xenon lamp 12 10 Ethanol None Xenon lamp 15 11 Toluene None Xenon lamp 16 12 2-Methyltetrahydrofuran None Xenon lamp 93

[0023] a Reaction condition: phenylboronic acid (1.0 mmol), air (1 atm), light source (15 W), solvent (3.0 mL), room temperature, 5 min, isolated yield. b Under nitrogen conditions. c Base (1.5 mmol),

[0024] We selected phenylboronic acid as a template substrate and screened the optimal reaction conditions (Table 1). The experimental results showed that, under the conditions of no photocatalyst, tetrahydrofuran as a solvent, air atmosphere and room temperature, and with ultraviolet lamp, blue / green LED lamp, incandescent lamp and xenon lamp as light sources, respectively, it was found that the expected product could be obtained in high yield (Examples 1-4). Among them, the yield of xenon lamp light source close to sunlight was 98%, and the control experiment in the dark condition did not achieve the expected effect, which confirmed the necessity of continuous irradiation of the light source (Example 6). When air was replaced by nitrogen, the reaction was terminated (Example 5), which indicated that air played an important role in the reaction. The present application tried to add organic base Et3N as an additive on the basis of Example 4, and the yield was significantly reduced (Example 7), which indicated that the addition of base would inhibit the reaction. The study on the solvent (Examples 9-12) showed that 2-methyltetrahydrofuran and tetrahydrofuran were the best solvents, and the yield was 93% and 98% respectively (Examples 4, 12). Therefore, 4 is the optimal reaction condition.

[0025] On the basis of the optimized reaction conditions, we extended the substrate scope of boronic acids (Table 2). Aromatic boronic acids containing different functional groups on the aromatic ring have been shown to be compatible under standard conditions and provide the corresponding hydroxylated products. Aromatic boronic acids with different substituents at the para position of the aromatic ring, including electron-donating groups such as alkyl (Example 15), alkoxy (Example 16), electron-withdrawing groups such as halogen (Example 18, 19), aldehyde (Example 25), nitro (Example 29), reacted well and provided the desired products under standard conditions. Notably, a tert-butyl group with large steric hindrance on the aromatic ring (Example 26) also adapted to the reaction conditions. Thus, from these results, it can be inferred that the electronic nature of the substituents has little effect on the efficiency of the reaction. In addition, the optimal reaction conditions are also applicable to fused rings, and the fused ring substrates can smoothly undergo aerobic hydroxylation without a photocatalyst to provide the corresponding products with yields of 92% and 94% (Example 23, Example 24).

[0026] Table 2. Implementation of different examples and yield of target producta

[0027]

[0028]

[0029] a Reaction conditions: boronic acid (1.0 mmol), air (1 atm), light source (15 W), solvent (3.0 mL), room temperature, 5 min, isolated yield.

[0030] The following is a specific description for Example 4 and Examples 13-30:

[0031] Example 4

[0032] 1.0 mmol of phenylboronic acid and 3 mL of tetrahydrofuran were sequentially added to the reaction bottle, and irradiated with a xenon lamp under room temperature and air conditions for 5 min. The reaction progress was tracked by thin layer chromatography. After the reaction was completed, 5.0 mL of HCl (2.0 M) was added to the reaction bottle, extracted with ethyl acetate (3 x 10 mL), and the organic phase was combined and washed with water twice. After drying with Na2SO4, the organic phase was filtered, concentrated, and separated by column chromatography to obtain the target product phenol with a yield of 98%. The structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 9.37 (s, 1H), 7.16-7.21 (m, 2H), 6.76-6.87 (m, 3H). 13C NMR (100 MHz, DMSO-d6) δ (ppm): 157.36, 129.35, 118.82, 115.26.

[0033] Example 13

[0034] Into a reaction flask, 1.0 mmol of 2-methylphenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product, 2-methylphenol, with a yield of 95%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.09-7.16 (m, 2H), 6.88 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 4.89 (s, 1H), 2.28 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ (ppm): 153.75, 131.07, 127.15, 123.80, 120.80, 114.94, 15.74

[0035] Example 14

[0036] Into a reaction flask, 1.0 mmol of 2-methylphenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product, 2-methylphenol, with a yield of 95%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.21 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 6.77 (d, J = 7.9 Hz, 2H), 6.50 (s, 1H), 2.38 (s, 3H). 13CNMR (100 MHz, CDC13) δ (ppm): 155.28, 140.01, 129.59, 121.86, 116.31, 112.56, 21.39.

[0037] Example 15

[0038] Into a reaction flask, 1.0 mmol of 4-methoxyphenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HCl (2.0 M) was added into the reaction flask, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-methoxyphenol with a yield of 99%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDC13) δ (ppm): 7.07 (d, J = 8.3 Hz, 2H), 6.78 (d, J = 8.4 Hz, 2H), 5.70 (s, 1H), 2.31 (s, 3H). 13 C NMR (100 MHz, CDC13) δ (ppm): 153.09, 130.16, 130.11, 115.24, 20.50

[0039] Example 16

[0040] Into a reaction flask, 1.0 mmol of 4-methoxyphenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HCl (2.0 M) was added into the reaction flask, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-methoxyphenol with a yield of 99%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDC13) δ (ppm): 6.77-6.81 (m, 4H), 5.08 (s, 1H), 3.77 (s, 3H). 13 C NMR (100 MHz, CDC13) δ (ppm): 153.59, 149.58, 116.17, 115.01, 55.94

[0041] Example 17

[0042] Into a reaction flask, 1.0 mmol of 2-fluorobenzoic acid and 3 mL of tetrahydrofuran were added successively, and irradiated with a xenon lamp at room temperature under air for 5 min. The reaction progress was tracked by thin layer chromatography. After the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, and extracted with ethyl acetate (3 x 10 mL). The organic phase was combined and washed with water twice, dried over Na2S04, filtered, concentrated, and separated by column chromatography to obtain the target product 2-fluorophenol with a yield of 93%. The structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDC13) δ (ppm): 7.02-7.11 (m, 3H), 6.85-6.89 (m, 1H), 5.88 (s, 1H). 13 C NMR (100 MHz, CDC13) δ (ppm): 152.19, 150.30, 143.55, 143.44, 124.89, 124.86, 120.94, 120.88, 117.47, 117.45, 115.70, 115.55.

[0043] Example 18

[0044] Into a reaction flask, 1.0 mmol of 2-fluorobenzoic acid and 3 mL of tetrahydrofuran were added successively, and irradiated with a xenon lamp at room temperature under air for 5 min. The reaction progress was tracked by thin layer chromatography. After the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, and extracted with ethyl acetate (3 x 10 mL). The organic phase was combined and washed with water twice, dried over Na2S04, filtered, concentrated, and separated by column chromatography to obtain the target product 2-fluorophenol with a yield of 93%. The structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDC13) δ (ppm): 7.02-7.11 (m, 3H), 6.85-6.89 (m, 1H), 5.88 (s, 1H). 13 C NMR (100 MHz, CDC13) δ (ppm): 152.19, 150.30, 143.55, 143.44, 124.89, 124.86, 120.94, 120.88, 117.47, 117.45, 115.70, 115.55.

[0045] Example 19

[0046] To a reaction flask was added 1.0 mmol of 4-chlorophenylboronic acid and 3 mL of tetrahydrofuran, which was irradiated with a xenon lamp at room temperature under air for 5 min, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, which was extracted with ethyl acetate (3 x 10 mL), the organic phase was combined and washed with water twice, dried with Na2S04, filtered, concentrated, and separated by column chromatography to obtain the target product 4-chlorophenol with a yield of 92%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDC13) δ (ppm): 7.16-7.13 (m, 2H), 6.72-6.75 (m, 2H), 5.08 (s, 1H). 13 C NMR (100 MHz, CDC13) δ (ppm): 153.94, 129.62, 125.75, 116.80

[0047] Example 20

[0048] To a reaction flask was added 1.0 mmol of 4-chlorophenylboronic acid and 3 mL of tetrahydrofuran, which was irradiated with a xenon lamp at room temperature under air for 5 min, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction flask, which was extracted with ethyl acetate (3 x 10 mL), the organic phase was combined and washed with water twice, dried with Na2S04, filtered, concentrated, and separated by column chromatography to obtain the target product 4-chlorophenol with a yield of 92%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.42 (s, 1H), 7.38 (d, J = 1.9 Hz, 1H), 7.15-7.17 (m, 1H), 6.96 (d, J = 8.7 Hz, 1H). 13 C NMR (100 MHz, DMSO-d6) δ (ppm): 152.27, 129.03, 127.80, 122.62, 120.60, 117.64.

[0049] Example 21

[0050] To a reaction vial, 1.0 mmol of 2-chloro-5-methylphenylboronic acid and 3 mL of tetrahydrofuran were added sequentially, and irradiated with a xenon lamp at room temperature under air for 5 min, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 2-chloro-5-methylphenol with a yield of 93%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 9.94 (s, 1H), 7.13-7.16 (m, 1H), 6.80 (s, 1H), 6.57 (d, J = 8.0 Hz, 1H), 2.34 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ (ppm): 152.71, 137.49, 129.33, 120.65, 117.18, 116.68, 20.49

[0051] Example 22

[0052] To a reaction vial, 1.0 mmol of 2-chloro-5-methylphenylboronic acid and 3 mL of tetrahydrofuran were added sequentially, and irradiated with a xenon lamp at room temperature under air for 5 min, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added to the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 2-chloro-5-methylphenol with a yield of 93%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 6.88 (s, 2H), 6.62 (s, 1H), 2.35 (s, 3H), 1.38 (s, 18H). 13 C NMR (100 MHz, DMSO-d6) δ (ppm): 151.48, 139.10, 127.94, 124.84, 21.01

[0053] Example 23

[0054] To a reaction flask, 1.0 mmol of a-naphthyl boronic acid and 3 mL of tetrahydrofuran were added sequentially, and irradiated with a xenon lamp at room temperature under air for 5 min. The reaction progress was tracked by thin layer chromatography. After the reaction was completed, 5.0 mL of HCl (2.0 M) was added to the reaction flask, and extracted with ethyl acetate (3 x 10 mL). The organic phase was combined and washed with water twice, dried over Na2SO4, filtered, concentrated, and separated by column chromatography to obtain the target product a-naphthol with a yield of 92%. The structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDCI3) δ (ppm): 8.19-822 (m, 1H), 7.82-7.85 (m, 1H), 7.46-7.52 (m, 3H), 7.31-7.34 (m, 1H), 6.82 (dd, J = 7.4, 0.5 Hz, 1H), 4.58 (s, 1H). 13 CNMR (100 MHz, CDCI3) δ (ppm): 151.38, 134.80, 127.71, 126.47, 125.86, 125.29, 124.39, 121.55, 120.73, 108.68.

[0055] Example 24

[0056] To a reaction flask, 1.0 mmol of a-naphthyl boronic acid and 3 mL of tetrahydrofuran were added sequentially, and irradiated with a xenon lamp at room temperature under air for 5 min. The reaction progress was tracked by thin layer chromatography. After the reaction was completed, 5.0 mL of HCl (2.0 M) was added to the reaction flask, and extracted with ethyl acetate (3 x 10 mL). The organic phase was combined and washed with water twice, dried over Na2SO4, filtered, concentrated, and separated by column chromatography to obtain the target product a-naphthol with a yield of 92%. The structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDCI3) δ (ppm): 8.19-822 (m, 1H), 7.82-7.85 (m, 1H), 7.46-7.52 (m, 3H), 7.31-7.34 (m, 1H), 6.82 (dd, J = 7.4, 0.5 Hz, 1H), 4.58 (s, 1H). 13C NMR (100 MHz, CDC13) δ (ppm): 153.35, 134.61, 129.87, 128.96, 127.78, 126.54, 126.39, 123.64, 117.77, 109.54

[0057] Example 25

[0058] Into a reaction vial, 1.0 mmol of 4-formylphenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-formylphenol with a yield of 90%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.57 (s, 1H), 9.77 (s, 1H), 7.74 (d, J = 8.1 Hz, 2H), 6.93 (d, J = 8.2 Hz, 2H). 13 C NMR (100 MHz, DMSO-d6) δ (ppm): 190.75, 163.29, 132.02, 128.40, 115.80

[0059] Example 26

[0060] Into a reaction vial, 1.0 mmol of 2-formylaminophenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 2-formylaminophenol with a yield of 89%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 13.03 (s, 1H), 8.40 (s, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.38 (t, J = 7.7 Hz, 1H), 6.82 - 6.89 (m, 2H). 13C NMR (100 MHz, DMSO-d6) d (ppm): 172.14, 161.10, 134.02, 128.08, 118.31, 117.39, 114.36

[0061] Example 27

[0062] Into a reaction vial, 1.0 mmol of 4-(benzyloxy carbonyl) phenyl boronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-(benzyloxy carbonyl) phenol with a yield of 87%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) d (ppm): 10.49 (s, 1H), 7.87 (d, J = 7.2 Hz, 2H), 7.33-7.45 (m, 5H), 6.88 (d, J = 7.2 Hz, 2H), 5.29 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) d (ppm): 165.39, 162.17, 136.47, 131.51, 128.44, 127.93, 127.81, 120.15, 115.39, 65.55

[0063] Example 28

[0064] Into a reaction vial, 1.0 mmol of 4-(benzyloxy carbonyl) phenyl boronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-(benzyloxy carbonyl) phenol with a yield of 87%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, CDCl3) d (ppm): 7.35 (t, J = 8.0 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.02-7.04 (m, 1H), 6.14 (s, 1H). 13C NMR (100 MHz, CDC13) δ (ppm): 155.4, 132.5, 132.25, 131.99, 131.73, 130.35, 118.87, 118.86, 117.85, 117.82, 112.36, 112.33.

[0065] Example 29

[0066] Into a reaction vial, 1.0 mmol of 4-methyl-3-nitrophenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-methyl-3-nitrophenol with a yield of 80%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.96 (s, 1H), 8.03 (s, 2H), 6.87 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ (ppm): 163.82, 139.55, 125.93, 115.57

[0067] Example 30

[0068] Into a reaction vial, 1.0 mmol of 4-methyl-3-nitrophenylboronic acid and 3 mL of tetrahydrofuran were added successively, irradiated by a xenon lamp, reacted for 5 min at room temperature under air, the reaction progress was tracked by thin layer chromatography, after the reaction was completed, 5.0 mL of HC1 (2.0 M) was added into the reaction vial, extracted with ethyl acetate (3 x 10 mL), the organic phase was combined, then the organic phase was washed with water twice, dried with no Na2S04, filtered, concentrated, and then separated by column chromatography to obtain the target product 4-methyl-3-nitrophenol with a yield of 80%, the structure of the product was identified by 1 H NMR and 13 C NMR. 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 10.96 (s, 1H), 8.03 (s, 2H), 6.87 (s, 2H). 13CNMR (100 MHz, DMSO-d6) δ (ppm): 156.02, 148.98, 133.44, 122.58, 120.81, 110.44, 18.71

[0069] Example 31

[0070] To the reaction flask was added 1.0 mmol of phenylboronic acid and 10 mL of a solution (equal amounts of tetrahydrofuran and 2-methyl-tetrahydrofuran) and irradiated with a xenon lamp for 30 minutes at room temperature under air. The reaction was followed by thin layer chromatography. After the reaction was complete, 5.0 mL of HCl (2.0 M) was added to the reaction flask and extracted with ethyl acetate (3 x 10 mL). The organic phases were combined and washed with water twice, dried over Na2SO4, filtered, concentrated, and separated by column chromatography to give the target product, phenol, in 98% yield.

[0071] Example 32

[0072] To the reaction flask was added 1.0 mmol of phenylboronic acid and 10 mL of a solution (equal amounts of tetrahydrofuran and 2-methyl-tetrahydrofuran) and irradiated with a xenon lamp for 30 minutes at room temperature under air. The reaction was followed by thin layer chromatography. After the reaction was complete, 5.0 mL of HCl (2.0 M) was added to the reaction flask and extracted with ethyl acetate (3 x 10 mL). The organic phases were combined and washed with water twice, dried over Na2SO4, filtered, concentrated, and separated by column chromatography to give the target product, phenol, in 98% yield.

[0073] While the preferred embodiments of the application have been described, additional variations and modifications can be made to the embodiments by those of skill in the art once given the benefit of the present disclosure without departing from the spirit and scope of the application. Therefore, it is to be understood that the present application is not to be limited to the specific examples set forth herein as the best mode of practicing the application. Rather, the scope of the application is to be accorded the broadest scope consistent with the principles and novel features disclosed herein.

[0074] Obviously, many modifications and variations of the present application are possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims and their equivalents, the application can be practiced otherwise than as specifically described.

Claims

1. A method for the production of phenols by the hydroxylation of boronic acid derivatives in air without the use of a photocatalyst and without the use of a base, characterized in that, The method comprises the following steps: The oxidation hydroxylation reaction of aryl boronic acid and ether solvent is carried out under light irradiation with oxygen in air as an oxidant under room temperature conditions, and a phenolic compound is obtained after the reaction is completed and post-processing is performed; the light source used for light irradiation is a xenon lamp; and the ether solvent is tetrahydrofuran.

2. A process for the production of phenols by the hydroxylation of boronic acid derivatives in the absence of a photocatalyst and in the absence of a base, according to claim 1, characterized in that, The reaction time is 5-60 min.

3. A process for the production of phenols by the hydroxylation of boronic acid derivatives in the absence of a photocatalyst and in the absence of a base, according to claim 2, characterized in that, The reaction time is 5 min.

4. A process for the production of phenol by hydroxylation of boronic acid derivatives in the absence of a photocatalyst and in the absence of a base, according to claim 1, characterized in that, The ratio of aryl boronic acid to ether solvent is 1 mmol: 1-10 mL.

5. A process for the production of phenols by the hydroxylation of boronic acid derivatives in the absence of a photocatalyst and in the absence of a base, according to claim 4, characterized in that, The ratio of aryl boronic acid to ether solvent is 1 mmol: 3 mL.

6. A process for the production of phenols by the hydroxylation of boronic acid derivatives in the absence of a photocatalyst and in the absence of a base, according to claim 1, characterized in that, The aryl boronic acid is one of phenyl boronic acid, o-methylphenyl boronic acid, m-methylphenyl boronic acid, p-methylphenyl boronic acid, 4-methoxyphenyl boronic acid, 2-fluorophenyl boronic acid, 4-fluorophenyl boronic acid, 4-chlorophenyl boronic acid, 2,4-dichlorophenyl boronic acid, 2-chloro-5-methylphenyl boronic acid, 2,6-di-tert-butyl-4-methylphenyl boronic acid, α-naphthyl boronic acid, β-naphthyl boronic acid, 4-aldehyde phenyl boronic acid, 2-formamide phenyl boronic acid, 4-(benzyloxy carbonyl) phenyl boronic acid, m-trifluoromethyl phenyl boronic acid, p-nitrophenyl boronic acid, 4-methyl-3-nitrophenyl boronic acid.

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