Method for preparing alpha-hydroxy-beta-keto ester compound by driving molecular oxygen through visible light on water

Abstract

The invention discloses a method for preparing an alpha-hydroxy-beta-keto ester compound by driving molecular oxygen on water through visible light, which comprises the following specific process: adding a beta-keto ester compound IIa into a solvent, and reacting with oxygen at 0-100 DEG C under the irradiation of visible light to prepare a target product alpha-hydroxy-beta-keto ester compound Ia. The method has the advantages that cheap water is used as a reaction medium, water reaction is combined with a photocatalytic oxidation strategy, molecular oxygen is used as an oxidizing agent, efficient alpha-hydroxylation reaction of the beta-keto ester compound without addition of metal, acid, alkali, photocatalyst and organic solvent is achieved, and the method is suitable for industrial production. And a green and efficient synthesis way is provided for preparing the alpha-hydroxyl beta-keto acid compound with wide application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of α-hydroxy-β-ketoester compounds, and particularly relates to a method for preparing α-hydroxy-β-ketoester compounds by visible light-driven molecular oxygen in water. Background Art

[0002] Water is the source of life, and many complex biosyntheses and life processes occur in water. Most fine chemical syntheses use petroleum-derived solvents, which generate a large amount of toxic waste, cause serious environmental pollution, and have high production costs. In recent years, it has been found that water has many significant advantages compared with other organic solvents. It can significantly reduce the reaction cost, simplify the process flow, and is environmentally friendly (Chem. Eur. J. 2020, 26, 9408; Chem. Sci., 2021, 12, 4237). Therefore, both in the industrial and academic fields, there is a desire to use water to replace common organic reagents to achieve green organic synthesis.

[0003] α-Hydroxy-β-ketoester compounds are a very important structural unit, widely present in natural products, pharmaceutical and pesticide intermediates. It is worth mentioning that methyl 5-chloro-1-oxoindene-2-hydroxy-2-carboxylate is an important intermediate for the highly effective pesticide indoxacarb. In 1981, Davis first reported a method for obtaining α-oxo-β-ketoester compounds using Davis reagent (Tetrahedron Lett. 1981, 22, 4385), which uses a stoichiometric amount of chiral oxidant and has a high cost. Currently, using an acid or a base as a catalyst and adding an oxidant in common organic solvents (such as dichloromethane, toluene, etc.) is the most common method for preparing such compounds. In 2014, the group of Jiaoning used cesium carbonate as a catalyst, oxygen as an oxidant, and triethyl phosphite as a reducing agent, and reacted in dimethyl sulfoxide to achieve the α-hydroxylation of a series of carbonyl compounds (Angew. Chem. Int. Ed., 2014, 126, 558–562). The research group of the inventors of this patent application also used water as a solvent, an organic peroxide as an oxidant, and tetrabutylammonium bromide as an additive in 2019 to achieve the highly efficient and highly selective α-hydroxylation of β-dicarbonyl compounds (Tetrahedron, 2019, 75, 3856), but this system still requires a stoichiometric amount of organic peroxide (cumene hydroperoxide, tert-butyl hydroperoxide, etc.) as an oxidant, and the reaction atom economy is not high. In recent years, the α-hydroxylation of β-ketoesters has made remarkable progress and has become one of the powerful methods for obtaining active hydroxy compounds (Advanced Synthesis & Catalysis 2024, 366, 3698-3738). From the perspective of green chemistry and sustainable development, the photocatalytic oxidation of molecular oxygen strategy is a green, environmentally friendly, highly efficient, and highly atom-economic oxidation method (Green Chemistry, 2018, 20, 4790). The present invention utilizes the photocatalytic oxidation of molecular oxygen strategy, further uses water as a reaction solvent to accelerate the reaction, and utilizes the unique advantages of reaction on water to achieve the highly efficient and highly selective α-hydroxylation of β-ketoester compounds, and there is no relevant report in this regard yet. Summary of the Invention

[0004] The technical problem solved by the present invention is to provide a method for preparing α-hydroxy-β-ketoester compounds by visible light-driven molecular oxygen in water. This method uses green and environmentally friendly water as the solvent, visible light as the driving force, and molecular oxygen as the oxidant to achieve highly efficient and highly selective β-ketoester α-hydroxylation reaction without the addition of metal, acid-base, photocatalyst, and organic solvent. This method has mild reaction conditions, simple operation, good substrate applicability, environmental friendliness, low cost, and is suitable for large-scale production.

[0005] The present invention adopts the following technical solutions to solve the above technical problems: A method for preparing α-hydroxy-β-ketoester compounds by visible light-driven molecular oxygen in water, characterized in that the specific process is: adding β-ketoester compound IIa to a solvent, and reacting with oxygen under visible light irradiation at 0-100 °C to obtain the target product α-hydroxy-β-ketoester compound Ia. The reaction equation in the synthesis process is:

[0006]

[0007] Wherein R 1 is alkyl, phenyl, substituted phenyl or benzyl, and the substituent on the benzene ring of the substituted phenyl is alkyl or alkoxy; R 2 is hydrogen, halogen, alkyl or alkoxy, and n is 1, 2 or 3;

[0008] The solvent is one or more of ultrapure water, distilled water, deionized water, tap water, natural mineral water and brine.

[0009] Further, the α-hydroxy-β-ketoester compounds Ia include:

[0010]

[0011]

[0012] Further, the light source of the visible light is sunlight or a 30W-LED energy-saving lamp.

[0013] Further, the reaction temperature in the reaction process is 10-30 °C.

[0014] Further, the source of the oxygen is air or pure oxygen at 1-10 atmospheres.

[0015] The present invention has the following advantages and beneficial effects compared with the prior art: The effectiveness of the present invention is reflected in that by using cheap water as the reaction medium, combining the "reaction on water" with the photocatalytic oxidation strategy, and using molecular oxygen as the oxidant, an efficient α-hydroxylation reaction of β-ketoester compounds without the addition of metal, acid, base, photocatalyst, and organic solvent is achieved, providing a green and efficient synthetic route for the preparation of α-hydroxy-β-keto acid compounds with wide application value. In addition, the post-treatment of this reaction is simple, and the reaction effect can still be maintained when scaled up to the gram level, showing broad prospects for production and application. Detailed implementation manners

[0016] The above content of the present invention will be further described in detail through the following examples. However, it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. Any technology implemented based on the above content of the present invention belongs to the scope of the present invention.

[0017] Example 1

[0018] Synthesis of hydroxylated product Ia-1:

[0019]

[0020] Weigh 0.1 mmol of methyl 1-indanone-2-carboxylate IIa-1 and put it into a 10 mL single-neck reaction tube. Add 2 mL of distilled water. Under the irradiation of a 30 W LED lamp (wavelength 390 nm), stir the reaction at room temperature in air. During the reaction, the solid in the system changes from dispersed particles to an emulsion. After reacting for 3 hours, the system changes from an emulsion to a clear solution, and white solid precipitates. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether: ethyl acetate = 5:1, v / v) to obtain the hydroxylated product Ia-1, namely methyl 2-hydroxy-1-indanone-2-carboxylate (17.5 mg, white solid, yield 85%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.77–7.67 (m, 1H), 7.61 (td, J = 7.5, 1.3 Hz, 1H), 7.46–7.31 (m, 2H), 3.92 (s, 1H), 3.71–3.62 (m, 4H), 3.19 (d, J = 17.3 Hz, 1H).

[0021] The inventive process implemented in Examples 2 - 8 is the same as that in Example 1, but the light sources listed in the following table are used instead of the LED lamp in Example 1. The results are shown in Table 1.

[0022] Table 1 Preparation of hydroxylated product Ia-1 using different light sources

[0023]

[0024] The invention process implemented in Examples 9 - 15 is the same as that in Example 1, but the solvents listed in the following table are used instead of distilled water in Example 1. The results are shown in Table 2.

[0025] Table 2 Preparation of hydroxylated product Ia - 1 using different solvents

[0026]

[0027] The invention process implemented in Examples 16 - 21 is the same as that in Example 9, but the temperatures listed in the following table are used instead of room temperature in Example 9. The results are shown in Table 3.

[0028] Table 3 Preparation of hydroxylated product Ia - 1 using different temperatures

[0029]

[0030] The invention process implemented in Examples 22 - 24 is the same as that in Example 9, but the oxygen concentrations listed in the following table are used instead of air in Example 9. The results are shown in Table 4.

[0031] Table 4 Preparation of hydroxylated product Ia - 1 using different oxygen concentrations

[0032]

[0033] Example 25

[0034] Preparation of hydroxylated product Ia - 2:

[0035]

[0036] Weigh 0.1 mmol of methyl 5 - chloro - 1 - indanone - 2 - carboxylate IIa - 2 and place it in a 10 mL single - neck reaction tube. Add 2 mL of ultrapure water. Under the irradiation of a 30 W LED lamp (wavelength 390 nm), stir and react in air at room temperature for 4 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to obtain the hydroxylated product Ia - 2, which is the intermediate of the pesticide indoxacarb (20.9 mg, white solid, yield 87%). 1 H NMR(400MHz,CDCl 3 )δ7.74(d,J = 8.2Hz,1H),7.50(d,J = 1.6Hz,1H),7.46–7.36(m,1H),4.02(s,1H),3.75(s,3H),3.71(d,J = 17.5Hz,1H),3.24(d,J = 17.5Hz,1H).

[0037] Example 26

[0038] Synthesis of hydroxylated product Ia-3:

[0039]

[0040] Weigh 0.1 mmol of methyl 4-chloro-1-indanone-2-carboxylate IIa-3 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction at room temperature in air for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 8:1, v / v) to obtain the hydroxylated product Ia-3 (20.5 mg, white solid, yield 86%). 1 H NMR(400MHz,CDCl 3 )δ7.68–7.56(m,2H),7.39–7.30(m,1H),3.94(s,1H),3.72–3.62(m,4H),3.15(d,J=17.9Hz,1H). 13 C NMR(101MHz,CDCl3)δ200.06,171.54,149.86,135.79,135.40,132.76,129.72,123.52,80.02,53.69,38.34。

[0041] Example 27

[0042] Synthesis of hydroxylated product Ia-4:

[0043]

[0044] Weigh 0.1 mmol of methyl 5,6-dichloro-1-indanone-2-carboxylate IIa-4 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction at room temperature in air for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 8:1, v / v) to obtain the hydroxylated product Ia-4 (22.2 mg, white solid, yield 81%). 1 H NMR(400MHz,CDCl 3 )δ7.80(s,1H),7.56(s,1H),3.93(s,1H),3.69(s,3H),3.61(d,J=17.5Hz,1H),3.14(d,J=17.5Hz,1H)。

[0045] Example 28

[0046] Synthesis of hydroxylated product Ia-5:

[0047]

[0048] Weigh 0.1 mmol of methyl 5,6-difluoro-1-indanone-2-carboxylate IIa-5 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to obtain the hydroxylated product Ia-5 (19.8 mg, slightly yellow solid, yield 81%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.51 (t, J = 7.9 Hz, 1H), 7.23 (dd, J = 9.2, 6.6 Hz, 1H), 3.92 (s, 1H), 3.69 (s, 3H), 3.61 (d, J = 17.5 Hz, 1H), 3.15 (d, J = 17.3 Hz, 1H).

[0049] Example 29

[0050] Synthesis of hydroxylated product Ia-6:

[0051]

[0052] Weigh 0.1 mmol of methyl 6-fluoro-1-indanone-2-carboxylate IIa-6 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to obtain the hydroxylated product Ia-6 (19.2 mg, white wax, yield 85%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.43–7.28 (m, 3H), 3.93 (s, 1H), 3.68 (s, 3H), 3.62 (d, J = 17.1 Hz, 1H), 3.15 (d, J = 16.8 Hz, 1H).

[0053] Example 30

[0054] Synthesis of hydroxylated product Ia-7:

[0055]

[0056] Weigh 0.1 mmol of methyl 4-(trifluoromethyl)-1-indanone-2-carboxylate IIa-7 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water, and under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 15:1, v / v) to obtain the hydroxylated product Ia-7 (22.1 mg, white solid, yield 81%). 1 H NMR(400MHz,CDCl 3 )δ7.90(dd,J=17.5,7.7Hz,2H),7.53(t,J=7.7Hz,1H),3.97(s,1H),3.84(d,J=18.1Hz,1H),3.70(s,3H),3.34(d,J=18.1Hz,1H).

[0057] Example 31

[0058] Synthesis of hydroxylated product Ia-8:

[0059]

[0060] Weigh 0.1 mmol of methyl 4-bromo-1-indanone-2-carboxylate IIa-8 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water, and under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to obtain the hydroxylated product Ia-8 (20.1 mg, white solid, yield 71%). 1 H NMR(400MHz,CDCl 3 )δ7.78(d,J=7.8Hz,1H),7.69(d,J=7.6Hz,1H),7.29(t,J=7.7Hz,1H),3.96(s,1H),3.70(s,3H),3.61(d,J=17.9Hz,1H),3.12(d,J=17.9Hz,1H).

[0061] Example 32

[0062] Synthesis of hydroxylated product Ia-9:

[0063]

[0064] Weigh 0.1 mmol of methyl 5-bromo-1-indanone-2-carboxylate IIa-9 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 12:1, v / v) to obtain the hydroxylated product Ia-9 (20.7 mg, white solid, yield 73%). 1 H NMR(400MHz,CDCl 3 )δ7.64–7.54(m,2H),7.54–7.49(m,1H),3.92(s,1H),3.70–3.59(m,4H),3.17(d,J=17.5Hz,1H).

[0065] Example 33

[0066] Synthesis of hydroxylated product Ia-10:

[0067]

[0068] Weigh 0.1 mmol of methyl 6-cyano-1-indanone-2-carboxylate IIa-10 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 4 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 12:1, v / v) to obtain the hydroxylated product Ia-10 (20.1 mg, white wax, yield 87%). 1 H NMR(400MHz,CDCl 3 )δ8.02(t,J=1.0Hz,1H),7.86(dd,J=8.0,1.6Hz,1H),7.58(dd,J=8.0,1.0Hz,1H),3.98(s,1H),3.78–3.61(m,4H),3.26(d,J=17.6Hz,1H).

[0069] Example 34

[0070] Synthesis of hydroxylated product Ia-11:

[0071]

[0072] Weigh 0.1 mmol of methyl 5-methoxy-1-indanone-2-carboxylate IIa-11 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction mixture in air at room temperature for 12 hours. Extract the reaction mixture twice with ethyl acetate and separate it by column chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to obtain the hydroxylated product Ia-11 (16.0 mg, pale yellow solid, yield 68%). 1 HNMR(400MHz,CDCl 3 δ7.67(d,J=8.6Hz,1H),6.94–6.79(m,2H),3.85(s,3H),3.67(s,3H),3.61(d,J=17.3Hz,1H),3.13(d,J=17.3Hz,1H).

[0073] Example 35

[0074] Synthesis of hydroxylated product Ia-12:

[0075]

[0076] Weigh 0.1 mmol of methyl 5-methyl-1-indanone-2-carboxylate IIa-12 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction mixture in air at room temperature for 12 hours. Extract the reaction mixture twice with ethyl acetate and separate it by column chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to obtain the hydroxylated product Ia-12 (15.3 mg, white solid, yield 64%). 1 H NMR(400MHz,CDCl 3 )δ7.62(d,J=7.9Hz,1H),7.22(s,1H),7.20–7.14(m,1H),3.91(s,1H),3.65(s,3H),3.59(d,J=12.9Hz,1H),3.13(d,J=17.3Hz,1H),2.40(s,3H).

[0077] Example 36

[0078] Synthesis of hydroxylated product Ia-13:

[0079]

[0080] Weigh 0.1 mmol of methyl 6-methoxy-1-indanone-2-carboxylate IIa-13 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to obtain the hydroxylated product Ia-13 (14.6 mg, white solid, yield 62%). 1 H NMR(400MHz,CDCl 3 )δ7.34–7.29(m,1H),7.22–7.17(m,1H),7.15(d,J=2.6Hz,1H),3.91(s,1H),3.78(s,3H),3.68(s,3H),3.58(d,J=16.9Hz,1H),3.11(d,J=16.9Hz,1H).

[0081] Example 37

[0082] Synthesis of hydroxylated product Ia-14:

[0083]

[0084] Weigh 0.1 mmol of methyl 6-methyl-1-indanone-2-carboxylate IIa-14 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 8:1, v / v) to obtain the hydroxylated product Ia-14 (15.3 mg, white solid, yield 67%). 1 H NMR(400MHz,CDCl 3 )δ7.53(s,1H),7.43(dd,J=7.9,1.7Hz,1H),7.31(d,J=7.9Hz,1H),3.89(s,1H),3.66(d,J=1.0Hz,3H),3.61(d,J=17.2Hz,1H),3.13(d,J=17.2Hz,1H),2.35(s,3H).

[0085] Example 38

[0086] Synthesis of hydroxylated product Ia-15:

[0087]

[0088] Weigh 0.1 mmol of benzyl 1-oxoindene-2-carboxylate IIa-15 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 6 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to obtain the hydroxylated product Ia-15 (22.0 mg, white solid, yield 80%). 1 H NMR(400MHz,CDCl 3 )δ7.80(d,J=7.7Hz,1H),7.69–7.62(m,1H),7.50–7.39(m,2H),7.32–7.26(m,3H),7.19–7.06(m,2H),5.22(d,J=12.4Hz,1H),5.12(d,J=12.4Hz,1H),4.21–3.85(m,1H),3.72(d,J=17.2Hz,1H),3.25(d,J=17.2Hz,1H).

[0089] Example 39

[0090] Synthesis of hydroxylated product Ia-16:

[0091]

[0092] Weigh 0.1 mmol of isopropyl 1-oxoindene-2-carboxylate IIa-16 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction in air at room temperature for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 12:1, v / v) to obtain the hydroxylated product Ia-16 (15.2 mg, white solid, yield 65%). 1 H NMR(400MHz,CDCl 3 )δ7.73(d,J=7.7Hz,1H),7.63–7.52(m,1H),7.46–7.29(m,2H),5.08–4.87(m,1H),3.96(s,1H),3.63(d,J=17.2Hz,1H),3.17(d,J=17.2Hz,1H),1.13(d,J=6.3Hz,3H),1.06(d,J=6.3Hz,3H).

[0093] Example 40

[0094] Synthesis of hydroxylated product Ia-17:

[0095]

[0096] Weigh 0.1 mmol of 2-adamantyl 1-indanone-2-carboxylate IIa-17 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction mixture in air at room temperature for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 15:1, v / v) to obtain 16.6 mg of the hydroxylated product Ia-17, a white solid, with a yield of 51%). 1 H NMR(400MHz,CDCl 3 )δ7.73(d,J=7.7Hz,1H),7.59(t,J=7.5Hz,1H),7.43(d,J=7.7Hz,1H),7.35(t,J=7.5Hz,1H),4.88(d,J=3.6Hz,1H),4.01(s,1H),3.64(d,J=17.0Hz,1H),3.23(d,J=17.0Hz,1H),1.88–1.39(m,11H),1.34–1.15(m,4H).

[0097] Example 41

[0098] Synthesis of hydroxylated product Ia-18:

[0099]

[0100] Weigh 0.1 mmol of methyl 1-tetralone-2-carboxylate IIa-18 and place it in a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under irradiation with a 30 W LED lamp (wavelength 390 nm), stir the reaction mixture in air at room temperature for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 15:1, v / v) to obtain 13.4 mg of the hydroxylated product Ia-18, a white solid, with a yield of 52%). 1 H NMR(400MHz,CDCl 3 )δ7.98(d,J=7.9Hz,1H),7.51–7.41(m,1H),7.29(t,J=7.6Hz,1H),7.22–7.16(m,1H),4.28(s,1H),3.68(d,J=1.1Hz,3H),3.06(q,J=5.1Hz,2H),2.72–2.58(m,1H),2.26–2.11(m,1H).

[0101] Example 42

[0102] Synthesis of hydroxylated product Ia-19:

[0103]

[0104] Weigh 0.1 mmol of compound IIa-19 and place it into a 10 mL single-neck reaction tube. Add 2 mL of ultrapure water. Under the irradiation of a 30 W LED lamp (wavelength 390 nm), stir the reaction at room temperature in air for 12 hours. The reaction mixture is extracted twice with ethyl acetate and separated by column chromatography (petroleum ether:ethyl acetate = 15:1, v / v) to obtain 13.6 mg of the hydroxylated product Ia-19, a white wax, with a yield of 58%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.43 (dd, J = 7.6, 1.5 Hz, 1H), 7.38–7.31 (m, 1H), 7.26–7.18 (m, 1H), 7.12 (d, J = 7.8 Hz, 1H), 4.35 (s, 1H), 3.61 (s, 3H), 2.99–2.75 (m, 2H), 2.54–2.36 (m, 1H), 2.05–1.82 (m, 3H).

[0105] Example 43

[0106] Scale-up preparation of the hydroxylated product Ia-2:

[0107]

[0108] Weigh 1.12 g (50 mmol) of methyl 5-chloro-1-indanone-2-carboxylate IIa-2 and place it into a 100 mL reaction flask. Add 50 mL of ultrapure water. Under the irradiation of a 300 W LED lamp (wavelength 390 nm), stir the reaction at room temperature in air. During the reaction, the solid in the system changes from dispersed particles to an emulsion. After 12 hours of reaction, the system changes from an emulsion to a clear solution, and a white solid precipitates. Directly filter the mixture by suction, and the obtained solid is recrystallized with ethyl acetate to obtain 0.94 g of the hydroxylated product Ia-2, with a yield of 79%.

[0109] Example 44

[0110] Scale-up preparation of the hydroxylated product Ia-2:

[0111]

[0112] Weigh 1.12 g (50 mmol) of methyl 5-chloro-1-indanone-2-carboxylate IIa-2 and place it into a 100 mL reaction flask. Add 50 mL of ultrapure water. Under the irradiation of a 1000 W incandescent lamp, stir the reaction at room temperature in air. During the reaction, the solid in the system changes from dispersed particles to an emulsion. After 24 hours of reaction, the system changes from an emulsion to a clear solution, and a white solid precipitates. Directly filter the mixture by suction, and the obtained solid is recrystallized with ethyl acetate to obtain 0.80 g of the hydroxylated product Ia-2, with a yield of 67%.

[0113] The basic principles, main features and advantages of the present invention have been shown and described above. Without departing from the spirit and scope of the present invention, various changes and improvements are possible to the present invention, and these changes and improvements fall within the scope of the present invention claimed.

Claims

1. A method for preparing α-hydroxy-β-keto acid ester compounds by using visible light to drive molecular oxygen on water, characterized in that The specific process is: adding β-ketoester compound IIa to a solvent, reacting with oxygen at 0-100°C under visible light irradiation to obtain the target product α-hydroxy-β-ketoester compound Ia. The reaction equation in the synthesis process is: Wherein R1 is an alkyl group, a phenyl group, a substituted phenyl group or a benzyl group, and the substituent on the phenyl ring of the substituted phenyl group is an alkyl group or an alkoxy group; R2 is hydrogen, a halogen group, an alkyl group or an alkoxy group, and n is 1, 2 or 3; The solvent is one or more of ultrapure water, distilled water, deionized water, tap water, natural mineral water and saline water.

2. The method for preparing α-hydroxy-β-ketoester compounds by using visible light driven molecular oxygen on water according to claim 1, characterized in that The α-hydroxy-β-keto acid ester compound Ia includes:

3. The method for preparing α-hydroxy-β-ketoester compounds by using visible light driven molecular oxygen on water according to claim 1, characterized in that: The light source of the visible light is sunlight or a 30W-LED energy-saving lamp.

4. The method for preparing α-hydroxy-β-ketoester compounds by using visible light driven molecular oxygen on water according to claim 1, characterized in that: The reaction temperature of the reaction process is 10-30°C.

5. The method for preparing α-hydroxy-β-ketoester compounds by using visible light driven molecular oxygen on water according to claim 1, characterized in that: The source of the oxygen is air or 1-10 atmospheres of pure oxygen.

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