Preparation method of visible light induced alpha-germanium oxime compound

Abstract

The invention belongs to the technical field of organic synthesis, focuses on innovation of a preparation method of an organic germanium compound, and particularly provides a novel photochemical synthesis path of an alpha-germanium oxime compound. According to the method, germane hydride, olefin and tert-butyl nitrite are taken as starting raw materials, and under the condition that no photocatalyst is added, only an ultraviolet light source is utilized for irradiation, so that the germanium-based / oximido-based bifunctionalization reaction of olefin is successfully realized for the first time. The method has the advantages of environmental friendliness, mild conditions, simplicity and convenience in operation, high atom economy, wide substrate application range and the like. The method can be used for modifying the drug molecule derivative after germanium group / oximidation, opens up a way for constructing an organic germanium compound with potential biological activity and pharmacological action, and is expected to play an important role in the field of medicine research and development.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and relates to the preparation of organogermanium compounds, specifically to a method for preparing visible light-induced α-germanium oxime compounds. Background Technology

[0002] Germanium possesses unique physicochemical properties such as significant stability, high hydrophobicity, large covalent radius, and low toxicity, which endow organogermanium compounds with broad application prospects. Specifically, organogermanium compounds can play an important role as key intermediates in drug development, serve as indispensable reaction modules to accelerate the preparation of advanced materials, and act as cross-coupling reagents to facilitate the construction of new chemical bonds. Traditional methods for synthesizing these compounds mainly rely on the use of strong nucleophiles such as organomagnesium / lithium, which suffers from drawbacks such as harsh reaction conditions, poor group tolerance, and insufficient reaction compatibility. Therefore, innovations in this field are expected to overcome the inherent defects of traditional methodologies, break through the structural limitations of the planar framework of existing two-dimensional organogermanium compounds, expand the three-dimensional spatial topology of aliphatic germananes, and endow germanium-containing drug candidates with superior pharmacokinetic properties.

[0003] Currently, using germane hydrides as radical precursors, a new route for the synthesis of alkyl germanes has been provided by achieving olefin radical hydrogenation and germanization reactions via photoinduced hydrogen atom transfer pathway. The shortcomings of this method are: (1) it requires the combined use of photocatalysts and hydrogen-snap agents, resulting in high experimental costs and hindering industrial production; (2) the products are mono-germanium-substituted derivatives with a simple structure, making it impossible to introduce other functional groups. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies for synthesizing aliphatic alkyl germanium compounds and to explore new modes of photochemical reactions of germanium-based free radicals, so as to expand its application in the construction of complex molecules, especially germanium-containing functional molecules.

[0005] The photochemical synthesis method of α-germanium-based oxime compounds involved in this invention is achieved through the following technical solution, with specific synthesis steps as follows: Germanium alkyl hydride, olefin, and tert-butyl nitrite are dissolved in a hexane / tert-butanol mixed solution. Subsequently, the above reaction system is irradiated with ultraviolet light. After the reaction is completed, the solvent is removed by extraction, drying, and rotary evaporation, and the target α-germanium-based oxime compound is obtained by column chromatography.

[0006] The specific reaction parameters are as follows: under a nitrogen atmosphere and irradiated with 390 nm ultraviolet light, the mixture is stirred at room temperature for 12 h; the molar ratio of germanium hydride, olefin, and tert-butyl nitrite is 3:1:10; the volume ratio of the n-hexane / tert-butanol mixed solution is 20:1; the stationary phase used for column chromatography is silica gel G; and the mobile phase is a mixture of petroleum ether and ethyl acetate.

[0007] The reaction equation for the preparation method is as follows:

[0008]

[0009] The structural formula of α-germanium oxime compounds is R includes any one or more of phenyl groups; EWG is an electron-withdrawing group, including any one or more of ester, aldehyde, ketone, amide, sulfonyl, and nitrile groups.

[0010] The structural formula of the germane hydride is as follows: Any one or more of them.

[0011] The structural formula of the olefin compound is as follows: Any one or more of them.

[0012] The structural formula of the tert-butyl nitrite is as follows:

[0013] The beneficial effects of this invention are:

[0014] This invention provides a novel method that eliminates the need for photocatalysts, hydrogen-snap agents, transition metal catalysts, and additives. It innovatively utilizes the spontaneous homolytic cleavage of tert-butyl nitrite under photoluminescence to generate tert-butoxy and nitroso radicals. Without a photocatalyst, a direct hydrogen atom transfer process is used to achieve the germanium / oxime bifunctionalization of olefins, resulting in the first synthesis of α-germanium oxime compounds with a three-dimensional structure. This method overcomes the product limitations of traditional photocatalytic germanium radical chemistry and offers advantages such as environmental friendliness, mild conditions, simple operation, high atom economy, and a wide range of applicable substrates. This method can be used for germanium / oxime modification of drug molecule derivatives, opening a pathway for constructing organogermanium compounds with potential biological and pharmacological activities, and is expected to play an important role in pharmaceutical research and development. Detailed Implementation

[0015] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0016] Example 1

[0017] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of methyl acrylate, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the methyl acrylate was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0018]

[0019] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (37 mg, 87% yield). 1 H NMR(400MHz,Chloroform-d)δ9.52(s,1H),7.53–7.50(m,6H),7.38–7.30(m,9H),3.47(s,3H),3.06(s,2H). 13 C NMR(101MHz,Chloroform-d)δ163.9,151.9,136.0,134.9,129.1,128.1,52.2,14.2.HRMS(ESI-TOF)m / z:[M+Na] + calcd forC 22 H 21 NO3NaGe + ,444.0625,found:444.0590.

[0020] Example 2

[0021] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of acrolein, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the acrolein was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0022]

[0023] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (20mg, 50% yield). 1 H NMR(400MHz,Chloroform-d)δ9.16(s,1H),8.05(s,1H),7.51–7.49(m,6H),7.39–7.34(m,9H),2.92(s,2H). 13 C NMR(101MHz,Chloroform-d)δ190.2,135.7,134.8,129.3,128.2,10.9.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 21 H 19 NO2NaGe + ,414.0520,found:414.0501.

[0024] Example 3

[0025] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of vinyl benzophenone, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the vinyl benzophenone was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0026]

[0027] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (31 mg, 67% yield). 1 H NMR (400MHz, Chloroform-d) δ8.65(s,1H),7.62–7.54(m,6H),7.47–7.34(m,10H),7.27–7.21(m,2H),7.21–7.15(m,2H),3.15(s,2H). 13C NMR(101MHz,Chloroform-d)δ191.8,159.3,136.6,136.1,134.9,132.2,129.7,129.2,128.2,127.8,12.9.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 27 H 23 NO2NaGe + ,490.0833,found:490.0838.

[0028] Example 4

[0029] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of acrylamide, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the acrylamide was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0030]

[0031] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (24mg, 53% yield). 1 H NMR (400MHz, Chloroform-d) δ7.56–7.48(m,6H),7.41–7.30(m,9H),3.68(s,0.5H),3.44(s,3H),3.26(s,0.5H),3.09(s,2H),2.85(s,3H). 13 C NMR(101MHz,Chloroform-d)δ154.6,136.2,134.9,129.1,61.0,26.1,14.8.HRMS(ESI-TOF)m / z:[M+H] + calcd for C 23 H 25 NO3Ge + ,451.1071,found:451.1070.

[0032] Example 5

[0033] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of benzenesulfonyl vinyl, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the benzenesulfonyl vinyl was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0034]

[0035] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (27 mg, 53% yield). 1 H NMR (400MHz, Chloroform-d) δ7.77(s,1H),7.60–7.51(m,6H),7.49–7.34(m,12H),7.29–7.23(m,2H),3.05(s,2H). 13 C NMR(101MHz,Chloroform-d)δ163.1,135.7,134.9,133.7,129.2,128.2,13.8.HRMS(ESI-TOF)m / z:[M+Na] + calcd forC 26 H 23 NO3NaSGe + ,526.0503,found:526.0511.

[0036] Example 6

[0037] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of acrylonitrile, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the acrylonitrile was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0038]

[0039] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (22mg, 57% yield). 1 H NMR (400MHz, Chloroform-d) δ8.24(s,1H),7.59–7.49(m,6H),7.49–7.38(m,9H),2.92(s,2H). 13 C NMR(101MHz,Chloroform-d)δ138.6,134.9,129.7,128.5,115.0,18.4.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 21 H 18 N2ONaGe + ,411.0523,found:411.0526.

[0040] Example 7

[0041] In a 10 mL Schlenk tube, 0.3 mmol of tricresylgermanane, 0.1 mmol of methyl acrylate, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the methyl acrylate was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0042]

[0043] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (43 mg, 91% yield). 1 H NMR (600MHz, Chloroform-d) δ8.73(s,1H),7.40–7.37(m,6H),7.18–7.12(m,6H),3.51(s,3H),3.02(s,2H),2.34(s,9H). 13C NMR(151MHz,Chloroform-d)δ164.0,152.3,138.9,134.8,132.5,128.9,52.3,21.5,14.4.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 25 H 27 NO3NaGe + ,486.1095,found:486.1104.

[0044] Example 8

[0045] In a 10 mL Schlenk tube, 0.3 mmol of trifluorophenylgermanane, 0.1 mmol of methyl acrylate, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the methyl acrylate was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0046]

[0047] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (24 mg, 50% yield). 1 H NMR(600MHz,Chloroform-d)δ9.26(s,1H),7.53–7.34(m,6H),7.11–6.96(m,6H),3.56(s,3H),3.02(s,2H). 13 C NMR (151MHz, Chloroform-d) δ 164.3 (d, J = 129.9Hz), 163.1, 151.5, 136.5 (d, J = 7.5Hz), 130.7 (d, J = 3.6Hz), 115.6, 115.5, 52.5, 14.4. 19 F NMR(565MHz,Chloroform-d)δ-111.11.HRMS(ESI-TOF)m / z:[M+H] + calcd forC 22 H 19 F3NO3Ge +,476.0523,found:476.0529.

[0048] Example 9

[0049] In a 10 mL Schlenk tube, 0.3 mmol of tri-n-butylgermanane, 0.1 mmol of benzyl acrylate, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After complete consumption of benzyl acrylate, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as eluent to obtain the target product.

[0050]

[0051] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (26 mg, 60% yield). 1 H NMR(600MHz,Chloroform-d)δ9.44(s,1H),7.40–7.37(m,2H),7.36–7.31(m,3H),5 .26(s,2H),2.27(s,2H),1.43–1.15(m,13H),0.92–0.83(m,9H),0.81–0.71(m,6H). 13 C NMR(151MHz,Chloroform-d)δ163.8,153.2,135.4,128.5,128.3.,67.2,27.0,26.4,13.7,13.7,12.9.HRMS(ESI-TOF)m / z:[M+H] + calcd for C 22 H 38 NO3Ge + ,438.2058,found:438.2087.

[0052] Example 10

[0053] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of sesamol methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the sesamol methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0054]

[0055] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (30mg, 57% yield). 1 H NMR (400MHz, Chloroform-d) δ7.67–7.54(m,6H),7.49–7.25(m,9H),6.66(d,J=8.0Hz,1H),6.29–6.12(m,2H),5.94(s,2H),3.13(s,2H). 13 C NMR(101MHz,Chloroform-d)δ162.6,151.3147.9,145.59,144.5,135.7,134.9,129.3,128.3,113.8,107.8,103.5,101.7,14.4.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 28 H 23 NO5NaGe + ,550.0680,found:550.0691.

[0056] Example 11

[0057] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of guaiacol methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the guaiacol methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0058]

[0059] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (26 mg, 50% yield). 1 H NMR(400MHz,Chloroform-d)δ9.47(s,1H),7.74–7.40(m,6H),7.51–7.20(m,9H),7 .33–7.15(m,1H),7.10–6.83(m,2H),6.68–6.57(m,1H),3.62(s,3H),3.13(s,2H). 13 C NMR(101MHz,Chloroform-d)δ161.8,151.2,151.1,139.4,135.9,134.9,129.2,128.2,127.1,122.7,120.6,112.4,55.8,14.4.HRMS(ESI-TOF)m / z:[M+Na] + calcdfor C 28 H 25 NO4NaGe + ,536.0888,found:536.0940.

[0060] Example 12

[0061] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of thymol methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the thymol methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0062]

[0063] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (29mg, 54% yield). 1 H NMR(600MHz,Chloroform-d)δ9.12(s,1H),7.59–7.49(m,3H),7.47–7.35(m,2H),7.35–7.30(m,3H),7.15–7.09 (m,1H),7.04–6.90(m,0H),6.22(s,0H),3.15(s,1H),2.64(p,J=6.9Hz,1H),2.26(s,1H),1.04(d,J=6.9Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.7,147.6,137.1,136.5,135.8,134.9,129.2, 128.2,127.4,126.3,122.4,26.8,23.1,20.7,14.5.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 31 H 31 NO3NaGe + ,562.1408,found:562.1419.

[0064] Example 13

[0065] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of cyclopropofol methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the cyclopropofol methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0066]

[0067] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (35mg, 49% yield). 1 H NMR(400MHz,Chloroform-d)δ9.83(s,1H),7.70–7.49(m,6H),7.49–7.30(m,9H),7.17–7.07(m,2H),6.93–6.78(m,2H ),4.19–4.13(m,2H),4.09–4.05(m,2H),3.06(s,2H),2.83(t,J=10.7,8.3Hz,1H),1.79(d,J=7.8Hz,2H),1.60(s,6H). 13 C NMR(101MHz,Chloroform-d)δ173.9,163.1,154.8,151.1,135.7,134.9,129.7,129.3,128. 4,128.2,118.9,79.2,62.7,62.6,60.9,34.8,25.9,25.4,14.1.HRMS(ESI-TOF)m / z:[M+NH4] + calcd for C 36 H 35 NO6NaCl2Ge + ,744.0945,found:744.0969.

[0068] Example 14

[0069] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of flurbiprofen methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the flurbiprofen methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0070]

[0071] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (29 mg, 43% yield). 1 H NMR(400MHz,Chloroform-d)δ9.22(s,1H),7.54–7.45(m,8H),7.43–7.38(m,3H),7.38–7.27(m,10H ),7.17–6.98(m,2H),4.16–3.91(m,4H),3.68(q,J=7.1Hz,1H),3.02(s,2H),1.48(d,J=7.2Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ173.7,163.2,160.9,158.4,151.4,141.4(d,J=7.6Hz),135.8,135.4,134.8,130.8(d,J=4.0H z), 129.2, 128.9 (d, J = 2.9Hz), 128.5, 128.2, 127.7, 123.6 (d, J = 3.3Hz), 115.3 (d, J = 23.6Hz), 62.8, 62.3, 44.8, 18.3, 14.0. 19 F NMR(376MHz,Chloroform-d)δ-117.44.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 38 H 34 NO5NaGe + ,700.1525,found:700.1525.

[0072] Example 15

[0073] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of methyl acrylate derivative of mefenamic acid, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the methyl acrylate derivative of mefenamic acid was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0074]

[0075] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (30 mg, 45% yield). 1 H NMR(400MHz,Chloroform-d)δ9.15(s,1H),7.91(d,J=8.1,1.6Hz,1H),7.60–7.44(m,6H),7.44–7.28(m,9H),7.25–7.18(m,2H),7.17–7 .06(m,2H),7.05–7.00(m,1H),6.72(d,J=8.5Hz,1H),6.61(t,J=7.5Hz,1H),4.32–4.21(m,4H),3.05(s,2H),2.32(s,3H),2.16(s,3H). 13 C NMR(101MHz,Chloroform-d)δ168.2,149.6,138.7,138.2,135.7,134.8,134.4,132.6,131.8,129.2 ,126.9,125.9,123.3,116.1,113.6,110.3,63.3,61.9,20.6,14.1,14.0.HRMS(ESI-TOF)m / z:[M+H] + calcd for C 38 H 37 N2O5Ge + ,675.1909,found:675.1943.

[0076] Example 16

[0077] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of ketoprofen methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the ketoprofen methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0078]

[0079] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (31 mg, 45% yield). 1 H NMR(400MHz,Chloroform-d)δ10.68(s,1H),7.80–7.71(m,2H),7.66–7.54(m,2H),7.48–7.42(m,10H),7.42–7 .26(m,10H),4.08–3.99(m,2H),3.84(q,J=8.0Hz,1H).3.80–3.68(m,2H),2.76(s,2H),1.51(d,J=7.2Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ196.7,173.7,163.1,147.5,140.6,137.9,137.4,135.4,134.1,132.7,13 1.5,130.2,129.4,129.3,129.1,128.5,128.4,62.7,61.8,45.2,18.4,18.3.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 39 H 35 NO6NaGe + ,710.1568,found:710.1632.

[0080] Example 17

[0081] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of dicamba methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the dicamba methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0082]

[0083] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (31 mg, 47% yield). 1 H NMR(400MHz,Chloroform-d)δ9.42(s,1H),7.56–7.46(m,6H),7.45–7.28(m,10H),7. 07(d,J=8.7Hz,1H),4.53–4.23(m,2H),4.23–4.10(m,2H),3.82(s,3H),3.04(s,2H). 13 C NMR(101MHz,Chloroform-d)δ164.2,163.2,153.9,151.4,135.7,134.1,132.0,129.8, 129.2,128.5,128.2,126.8,125.8,63.2,62.8,62.3,14.0.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 31 H 27 NO6NaCl2Ge + ,676.0319,found:676.0336.

[0084] Example 18

[0085] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of ibuprofen methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the ibuprofen methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0086]

[0087] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (39 mg, 61% yield). 1 H NMR(400MHz,Chloroform-d)δ9.70(s,1H),7.66–7.51(m,6H),7.45–7.29(m,9H),7.27–7.17(m,2H),7.16–7.05(m,2H),4.12–3.88 (m,4H),3.69(q,J=7.2Hz,1H),3.02(s,2H),2.40(d,J=7.0Hz,2H),1.96–1.80(m,1H),1.44(d,J=7.0Hz,3H),0.87(d,J=6.6Hz,6H). 13 CNMR(101MHz,Chloroform-d)δ174.5,163.2,151.3,140.7,137.4,135.8,134.8,129.4,129 .2,128.2,127.2,62.9,61.9,45.0,44.9,30.2,22.4,18.5,14.0.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 36 H 39 NO5NaGe + ,662.1932,found:662.1949.

[0088] Example 19

[0089] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of naproxen methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the naproxen methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0090]

[0091] Purification by flash column chromatography (PE:EA, v / v=5:1). Colorless oil (37mg, 56% yield). 1 H NMR(400MHz,Chloroform-d)δ9.75(s,1H),7.78–7.57(m,4H),7.52–7.39(m,6H),7.39–7.23(m,5H),7.14–7.03(m, 2H),4.14–4.01(m,2H),4.01–3.93(m,2H),3.84(s,3H),3.78(q,J=7.1Hz,1H),2.91(s,2H),1.53(d,J=7.2Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ174.4,163.2,157.7,151.1,135.8,135.3,133.8,129.4,129.3,128.9,12 8.2,127.3,126.2,126.1,119.1,105.7,62.9,62.1,55.3,45.3,18.5,13.9.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 37 H 35 NO6NaGe + ,686.1568,found:686.1574.

[0092] Example 20

[0093] In a 10 mL Schlenk tube, 0.3 mmol of triphenylgermanane, 0.1 mmol of aceclofenac methyl acrylate derivative, and 1 mmol of tert-butyl nitrite were stirred thoroughly in 1.5 mL of a hexane / tert-butanol mixed solvent (v / v = 20 / 1). The reaction mixture was then continuously irradiated for 12 h under a nitrogen atmosphere and at room temperature using a 390 nm LED lamp (20 W). After the aceclofenac methyl acrylate derivative was completely consumed, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel chromatography using petroleum ether / ethyl acetate as the eluent to obtain the target product.

[0094]

[0095] Purification by flash column chromatography (PE: EA, v / v = 5:1). Colorless oil (39 mg, 49% yield). 1 H NMR(400MHz,Chloroform-d)δ9.40(s,1H),7.62–7.43(m,7H),7.42–7.27(m,10H),7.26–7.19(m,1H),7.17–7.04(m ,1H),6.99–6.88(m,2H),6.62–6.50(m,1H),4.54(s,2H),4.13–4.01(m,4H),3.90(s,2H),3.04(s,2H),2.03(s,1H). 13 C NMR(101MHz,Chloroform-d)δ171.4,167.2,163.2,151.4,142.8,137.9,135.7,134.9,131.0,129.6 ,129.3,128.9,124.1,123.9,122.2,118.5,62.7,62.5,60.9,38.0,14.1.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 39 H 34 N2O7NaCl2Ge + ,809.0847,found:809.0856.

[0096] Although embodiments of the invention have been disclosed for illustrative purposes, those skilled in the art will understand that various substitutions, variations, and modifications are possible without departing from the spirit and scope of the invention and the appended claims. Therefore, the scope of the invention is not limited to the contents disclosed in the embodiments.

Claims

1. A method for preparing visible light-induced α-germanium-based oxime compounds, characterized in that: The method involves dissolving germane hydride, olefin compounds, and tert-butyl nitrite in a hexane / tert-butanol mixed solution. Subsequently, the reaction system is irradiated with ultraviolet light. After the reaction is completed, the solvent is removed by extraction, drying, and rotary evaporation. The target α-germanium oxime compound is then obtained by column chromatography.

2. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The structural formula of the α-germanium-based oxime compound is as follows: R includes any one or more of phenyl or n-butyl groups; EWG is an electron-withdrawing group, including any one or more of ester, aldehyde, ketone, amide, sulfonyl, and nitrile groups.

3. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The structural formula of the germane hydride is as follows: Any one or more of them.

4. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The structural formula of the olefin compound is as follows: Any one or more of them.

5. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The structural formula of the tert-butyl nitrite is as follows:

6. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The reaction conditions were: stirring at room temperature for 12 hours under a nitrogen atmosphere and irradiation with 390 nm ultraviolet light.

7. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The molar ratio of the germane hydride, olefin compound, and tert-butyl nitrite is 3:1:

10.

8. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The volume ratio of the n-hexane / tert-butanol mixed solution is 20:

1.

9. The method for preparing a visible light-induced α-germanium-based oxime compound according to claim 1, characterized in that: The stationary phase used in the column chromatography separation is silica gel G, and the mobile phase is a mixture of petroleum ether and ethyl acetate.

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