CN109761943B - Synthesis method of C-3 alkyl substituted coumarin derivative - Google Patents
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Abstract
The invention discloses a method for synthesizing C-3 alkyl substituted coumarin derivatives, which comprises the steps of preparing coumarin derivatives shown in a formula (I) and coumarin derivatives shown in a formula (II)NDissolving an alkanoyloxy phthalimide compound, a photocatalyst and protonic acid in an organic solvent, reacting for 3-36h at the temperature of 20-60 ℃ under the irradiation of visible light, and after the reaction is finished, carrying out post-treatment on a reaction system to obtain a C-3 alkyl substituted coumarin derivative target product shown in a formula (III); the reaction formula is as follows:
in the formulae (I) and (III), the substituent R1Is H, methyl, methoxy, fluorine, chlorine or bromine; in the formulae (II) and (III), the substituent R2Is a linear alkyl or cycloalkyl of C1-C8. The method takes light as reaction energy to realize C-3 alkylation of coumarin, so that the reaction is safer and more green, the cost is lower, the application range of substrates of the reaction is expanded, and the synthesis method of C-3 substituted coumarin compounds is enriched.
Description
Technical Field
The invention relates to a method for synthesizing C-3 alkyl substituted coumarin derivatives.
Background
Coumarin derivatives are an important natural compound, and widely exist in the plant world. Research shows that the coumarin compound has good biological activity, has obvious effects on antibiosis, anti-inflammation, anticancer and anti-HIV virus, and has wide application in the field of medicine. In addition, the good optical performance of the coumarin compound also makes the coumarin compound have an important position in the field of organic optical materials. In recent years, the synthesis of 3-substituted coumarin derivatives has attracted much attention and has been advanced to some extent.
The existing synthesis method of the 3-substituted coumarin derivative mainly comprises the following steps: obtaining alkylated coumarin through two-component or multi-component cyclization, introducing olefin or arene on coumarin C-3 through metal palladium catalysis, and introducing cycloparaffin and ether at coumarin C-3 position through metal iron or cobalt catalysis; TBHP is used as an oxidant, and alkylation of coumarin C-3 is realized without metal catalysis. The reported coumarin C-3 functionalized method usually needs higher reaction temperature, harsh conditions and large energy consumption. In addition, the existing method can only introduce aryl, alkenyl, cycloalkyl and ether free radicals on coumarin C-3, is not suitable for more difficult saturated straight-chain alkyl, and has certain limitation on substrates.
The photochemical reaction is an important direction for green chemical development in recent years, avoids harsh conditions such as high temperature and high pressure in traditional thermochemistry, has the characteristics of atom economy, high catalytic efficiency and the like, and has become one of the research hotspots in the field of organic synthesis in recent years.
Disclosure of Invention
Aiming at the technical problems in the prior art, the invention aims to provide a simple, efficient, safe and environment-friendly method for synthesizing C-3 alkyl substituted coumarin derivatives.
The method for synthesizing the C-3 alkyl substituted coumarin derivative shown in the formula (III) is characterized in that the coumarin derivative shown in the formula (I), the N-alkanoyloxy phthalimide compound shown in the formula (II), a photocatalyst and protonic acid are dissolved in an organic solvent and react for 3-36 hours at the temperature of 20-60 ℃ under the irradiation of visible light, and after the reaction is finished, a reaction system is subjected to post-treatment to obtain a C-3 alkyl substituted coumarin derivative target product shown in the formula (III); the reaction formula is as follows:
in the formulae (I) and (III), the substituent R1Is H, methyl, methoxy, fluorine, chlorine or bromine;
in the formulae (II) and (III), the substituent R2Is a linear alkyl or cycloalkyl of C1-C8.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the mass ratio of the N-alkanoyloxy phthalimide compound shown in the formula (II) to the coumarin derivative shown in the formula (I) is 1-4: 1, and preferably 1-2: 1.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the mass ratio of the coumarin derivative shown in the formula (I) to the photocatalyst is 1: 0.01-0.1, and preferably 1: 0.01-0.05.
The synthesis method of the C-3 alkyl substituted coumarin derivative is characterized in that the photocatalyst is Ir (ppy)3。
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the protonic acid is trifluoroacetic acid or trifluoromethanesulfonic acid, and preferably trifluoroacetic acid.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the mass ratio of the protonic acid to the coumarin derivative shown in the formula (I) is 0.2-1: 1, and preferably 0.4-1: 1.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the visible light is white light or blue light, preferably white light.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the reaction temperature is 20-40 ℃, and the organic solvent is DMF or DMSO, preferably DMSO.
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that a reaction system is subjected to post-treatment and comprises the following steps: adding water and an organic extractant into a reaction system for extraction, separating liquid into an organic layer and a water layer, drying the organic layer by anhydrous sodium sulfate, removing the solvent by decompression concentration, separating the concentrated residue by column chromatography, collecting eluent containing a target product by taking a mixed solvent of petroleum ether and ethyl acetate as an eluent, and evaporating the solvent to obtain the target product of the C-3 alkyl substituted coumarin derivative shown in the formula (III).
The method for synthesizing the C-3 alkyl substituted coumarin derivative is characterized in that the organic extracting agent is dichloromethane or ethyl acetate, preferably dichloromethane; in the mixed solvent of the petroleum ether and the ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 8-30: 1.
Compared with the prior art, the invention has the beneficial effects that:
1) the method realizes the C-3 alkylation of the coumarin by using light as reaction energy, so that the reaction is safer and more green, and the cost is lower.
2) The method has the advantages of good reaction selectivity, simple and convenient operation and high product yield.
3) According to the invention, saturated straight-chain alkyl can be introduced into coumarin C-3, so that straight-chain alkylation reaction of C-3 position of coumarin is realized, the application range of a substrate for the reaction is expanded, and the synthesis method of C-3 substituted coumarin compounds is enriched.
In conclusion, the invention provides a synthesis method of a photocatalytic C-3 alkyl substituted coumarin derivative. The method has the advantages of easily available raw materials, simple and convenient operation, good substrate applicability, economy, environmental protection and the like, and is a green chemical synthesis method with better application prospect.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
Example 1
Coumarin (0.5mmol,73mg), N- (2, 2-dimethyl) propionyloxyphthalimide (1.0mmol,247mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoroacetic acid (0.25mmol,28.5mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the mixture was stirred in N2The reaction was carried out under 3w white light irradiation at 25 ℃ for 24h under the protection of atmosphere. After the reaction, the reaction system was washed with water, extracted with dichloromethane, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing the target compound by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1 as eluent, evaporating the solvent and drying to obtain 81.9mg of white crystal 3-tert-butyl coumarin with the yield of 81 percent, wherein the chemical structural formula is as follows:
characterization data: white solid, melting point: the temperature of the mixture is between 82.1 and 82.4 ℃,1H NMR(400MHz,CDCl3)δ7.55(s,1H),7.45(t,J＝7.4Hz,2H),7.33-7.17(m,2H),1.40(s,9H)；13C NMR(100MHz,CDCl3)δ159.9,153.2,137.0,136.6,130.5,127.6,124.0,119.4,116.0,35.0,28.6。
example 2
The protonic acid (trifluoroacetic acid) in the system was replaced with trifluoromethanesulfonic acid (0.25mmol,37.5mg), and the other operations were performed as in example 1 to obtain 76mg of 3-tert-butylcoumarin as a white solid in a yield of 75%.
Example 3
The charge of N- (2, 2-dimethyl) propionyloxy phthalimide was changed to 0.5mmol, and the other operations were performed in the same manner as in example 1 to obtain 58mg of 3-t-butylcoumarin as a white solid in a yield of 57%.
Example 4
A photocatalyst (Ir (ppy)3) The amount was changed to 0.02mmol, and the other operations were performed in the same manner as in example 1 to obtain 76mg of 3-t-butylcoumarin as a white solid in a yield of 57%.
Example 5
The light source of the system was changed to 3w blue light, and the other operations were performed in the same manner as in example 1 to obtain 67mg of white crystalline 3-t-butylcoumarin with a yield of 66%.
Example 6
The amount of TFA (trifluoroacetic acid) was increased to 0.5mmol (57mg), and the other operations were performed as in example 1 to obtain 72mg of white crystalline 3-t-butylcoumarin with a yield of 71%.
Example 7
The solvent in the reaction system was replaced with the same amount of DMF, and the other operations were performed as in example 1 to obtain 52mg of 3-t-butylcoumarin as a white crystal with a yield of 51%.
Example 8
The reaction time was shortened to 6h and the other operations were performed as in example 1 to obtain 78mg of 3-tert-butylcoumarin as white crystals in a yield of 77%.
Example 9
Mixing coumarin (0.5mmol,73mg), N-acetoxyphthalimide (1.0mmol,205mg), Ir (ppy)3(0.025mmol,16.4mg) and trifluoroacetic acid (0.5mmol,57mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the mixture was stirred under N2Atmosphere(s)Under protection, the reaction was carried out for 24h under 3w white light irradiation and at a temperature of 20 ℃. After the reaction, the reaction system was washed with water, extracted with dichloromethane, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 25:1 as an eluent, collecting an eluent containing a target compound, evaporating to remove the solvent, and drying to obtain 57mg of white crystal 3-methylcoumarin, wherein the yield is 71%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: the temperature of the mixture is between 89.6 and 90.3 ℃,1H NMR(400MHz,CDCl3)δ7.52(s,1H),7.46(t,J＝8.0Hz,1H),7.42(d,J＝7.6Hz,1H),7.30(d,J＝8.4Hz,1H),7.25(t,J＝7.6Hz,1H),2.22(s,3H)；13C NMR(100MHz,CDCl3)δ154.9,146.0,131.9,123.2,119.7,118.6,117.0,112.3,109.2,9.9。
example 10
Coumarin (0.5mmol,73mg), N-N-butyroyloxyphthalimide (0.6mmol,148mg), Ir (ppy)3(0.015mmol,9.8mg) and trifluoroacetic acid (0.3mmol,34mg) were charged in a 5mL single-neck reaction flask, DMF (1.0mL) was added as a solvent, and the reaction was carried out in N2The reaction was carried out under 3w white light irradiation at a temperature of 35 ℃ for 12h under the protection of an atmosphere. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing a target compound by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1 as an eluent, evaporating the solvent, and drying to obtain 66mg of white crystal 3-butyl coumarin, wherein the yield is 65%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: the temperature of the mixture is between 47.6 and 48.3 ℃,1H NMR(400MHz,CDCl3)δ7.48(s,1H),7.47-7.41(m,2H),7.30(d,J＝8.4Hz,1H),7.25(t,J＝7.6Hz,1H),2.55(t,J＝7.6Hz,2H),1.79-1.58(m,2H),1.00(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3)δ161.8,153.1,138.5,130.4,129.8,127.1,124.2,119.6,116.4,32.8,21.2,13.7。
example 11
Coumarin (0.5mmol,73mg), N-N-nonanoyloxyphthalimide (0.75mmol,238mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoromethanesulfonic acid (0.2mmol,30mg) were added to a 5mL single-neck reaction flask, DMF (1.0mL) was added as solvent, and the mixture was stirred under N2Under the protection of atmosphere, the reaction is carried out for 10 hours under the irradiation of 3w of blue light and at the temperature of 40 ℃. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1 as an eluent, collecting an eluent containing a target compound, evaporating to remove the solvent, and drying to obtain 66mg of white crystal 3-n-octyl coumarin, wherein the yield is 51%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: the temperature of the mixture is 63.3-64.1 ℃,1H NMR(400MHz,CDCl3)δ7.51-7.39(m,3H),7.30(d,J＝8.4Hz,1H),7.24(t,J＝7.6Hz,1H),2.56(t,J＝7.6Hz,2H),1.73-1.56(m,2H),1.48-1.17(m,10H),0.88(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3)δ161.8,153.1,138.3,130.4,130.1,127.1,124.2,119.6,116.4,31.8,30.8,29.4,29.3,29.2,28.0,22.6,14.1。
example 12
Coumarin (0.5mmol,73mg), N- (2-methyl) propionyloxyphthalimide (0.75mmol,238mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoromethanesulfonic acid (0.25mmol,37.5mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the mixture was stirred under N2Under atmosphere protection, under 3w white light irradiation andthe reaction is carried out for 24h at the temperature of 25 ℃. After the reaction, the reaction system was washed with water, extracted with dichloromethane, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing a target compound by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1 as an eluent, evaporating the solvent, and drying to obtain 82mg of white crystal 3-isopropyl coumarin, wherein the yield is 87%, and the chemical structural formula of the yellow oily substance is as follows:
characterization data: white solid, melting point: the temperature of the mixture is 52.8-53.4 ℃,1H NMR(400MHz,CDCl3)δ7.57-7.40(m,3H),7.37-7.15(m,2H),3.22-3.05(m,1H),1.27(d,J＝7.2Hz,6H)；13C NMR(100MHz,CDCl3)δ161.4,152.8,135.9,135.7,130.5,127.3,124.2,119.6,116.3,28.7,21.4。
example 13
Coumarin (0.5mmol,73mg), N-cyclohexylformyloxyphthalimide (1.0mmol,273mg), Ir (ppy)3(0.02mmol,13mg) and trifluoroacetic acid (0.3mmol,34.2mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the mixture was stirred under N2Under the protection of atmosphere, the reaction is carried out for 12 hours under the irradiation of 3w of blue light and at the temperature of 25 ℃. After the reaction, the reaction system was washed with water, extracted with dichloromethane, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing the target compound by using a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20:1 as an eluent, evaporating the solvent, and drying to obtain 68mg of white crystal 3-cyclohexyl coumarin, wherein the yield is 60%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: the temperature of the mixture is between 86.6 and 87.5 ℃,1H NMR(400MHz,CDCl3)δ7.48-7.40(m,3H),7.29(d,J＝8.4Hz,1H),7.24(t,J＝7.6Hz,1H),2.78(tt,J＝11.6,2.8Hz,1H),1.98(d,J＝12.0Hz,2H),1.85(d,J＝13.2Hz,2H),1.77(d,J＝13.2Hz,1H),1.53-1.37(m,2H),1.37-1.21(m,3H)；13C NMR(100MHz,CDCl3)δ161.51,152.7,136.3,134.9,130.4,127.3,124.1,119.7,116.3,38.2,32.1,26.5,26.2。
example 14
A mixture of 6-fluorocoumarin (0.5mmol,82mg), N- (2, 2-dimethyl) propionyloxyphthalimide (1.0mmol,247mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoroacetic acid (0.25mmol,28.5mg) were added to a 5mL single-neck reaction flask, DMF (1.0mL) was added as a solvent, and the mixture was stirred under N2The reaction was carried out under 3w white light irradiation at 25 ℃ for 36h under the protection of atmosphere. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing a target compound by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 15:1 as an eluent, evaporating the solvent, and drying to obtain 39mg of white crystal 6-fluoro-3-tert-butyl coumarin, wherein the yield is 35%, and the chemical structural formula is as follows:
white crystals, melting point: 158-161 ℃;1HNMR(400MHz,CDCl3)δ7.49(s,1H),7.26(dd,J＝8.9,4.3Hz,1H),7.23-7.12(m,2H),1.40(s,9H)；13C NMR(100MHz,CDCl3)δ159.5,158.6(d,J＝243.1Hz),149.3(d,J＝1.9Hz),138.4,135.7(d,J＝2.8Hz),120.1(d,J＝9.0Hz),117.9(d,J＝24.5Hz),117.4(d,J＝8.4Hz),112.8(d,J＝23.8Hz),35.2,28.6。
example 15
Coupling 6-bromocoumarin (0.5mmol,112mg), N- (2, 2-dimethyl) propionyloxyphthalimide (1.0mmol,247mg), Ir (ppy)3(0.005mmol,3.3mg) and trifluoroacetic acid (0.4mmol,45.6mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the reaction was carried out under N2Atmosphere protectionThe reaction was carried out for 36h under 3w white light irradiation and at a temperature of 25 ℃. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 15:1 as an eluent, collecting an eluent containing a target compound, evaporating to remove the solvent, and drying to obtain 57mg of white crystal 6-bromo-3-tert-butyl coumarin, wherein the yield is 41%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: 130 ℃ and 133 ℃;1HNMR(400MHz,CDCl3)δ7.60(d,J＝2.4Hz,1H),7.53(dd,J＝8.8,2.4Hz,1H),7.46(s,1H),7.17(d,J＝8.8Hz,1H),1.39(s,9H)；13C NMR(100MHz,CDCl3)δ159.2,152.0,138.4,135.3,133.3,129.9,121.0,117.7,116.5,35.3,28.6。
example 16
A mixture of 7-methoxycoumarin (0.5mmol,112mg), N- (2, 2-dimethyl) propionyloxyphthalimide (0.9mmol,222mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoroacetic acid (1.0mmol,114mg) were charged in a 5mL single-neck reaction flask, DMF (1.0mL) was added as solvent, and the mixture was stirred under N2The reaction was carried out under 3w white light irradiation at 20 ℃ for 8h under the protection of atmosphere. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing the target compound by using mixed liquid of petroleum ether and ethyl acetate with the volume ratio of 10:1 as eluent, evaporating the solvent and drying to obtain 87mg of white crystal 7-methoxy-3-tert-butyl coumarin, wherein the yield is 75%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: 151.2-152.0℃；1HNMR(400MHz,CDCl3)δ7.48(s,1H),7.34(d,J＝8.8Hz,1H),6.93-6.73(m,2H),3.86(s,3H),1.38(s,9H)；13C NMR(100MHz,CDCl3)δ161.8,160.2,154.8,136.7,133.5,128.5,113.1,112.2,100.0,55.7,34.8,28.7。
Example 17
A mixture of 6-methylcoumarin (0.5mmol,108mg), N- (2, 2-dimethyl) propionyloxyphthalimide (0.6mmol,148mg), Ir (ppy)3(0.02mmol,13mg) and trifluoroacetic acid (0.25mmol,57mg) were added to a 5mL single-neck reaction flask, DMSO (1.0mL) was added as a solvent, and the reaction was carried out in N2The reaction was carried out under 3w white light irradiation at 25 ℃ for 12h under the protection of atmosphere. After the reaction, the reaction system was washed with water, extracted with ethyl acetate, and then separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing the target compound by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1 as eluent, evaporating the solvent and drying to obtain 66mg of white crystal 6-methyl-3-tert-butyl coumarin, wherein the yield is 61%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: 84.1-85.5 ℃;1HNMR(400MHz,CDCl3)δ7.49(s,1H),7.29-7.22(m,2H),7.17(d,J＝8.8Hz,1H),2.39(s,3H),1.39(s,9H)；13C NMR(100MHz,CDCl3)δ160.1,151.3,136.9,136.6,133.6,131.5,127.5,119.2,115.7,35.0,28.6,20.8.
example 18
A mixture of 8-chlorocoumarin (0.5mmol,108mg), N- (2, 2-dimethyl) propionyloxyphthalimide (1.0mmol,247mg), Ir (ppy)3(0.01mmol,6.5mg) and trifluoroacetic acid (0.25mmol,57mg) were added to a 5mL single-neck reaction flask, and DMSO (1.0mL) was added as a solvent in the presence of N2The reaction is carried out under the protection of atmosphere and is carried out for 30 hours under the irradiation of 3w of blue light and at the temperature of 25 ℃. After the reaction is finished, the reaction system is washed by water and extracted by ethyl acetate, and then liquid is separated into an organic layer and a water layer, and the organic layer is formedAfter the layer was dried over anhydrous sodium sulfate, the solvent was removed by distillation and concentration under reduced pressure to give a yellow oil. Separating the yellow oily substance by column chromatography, collecting eluent containing the target compound by using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 15:1 as an eluent, evaporating the solvent, and drying to obtain 50mg of white crystal 8-chloro-3-tert-butyl coumarin, wherein the yield is 42%, and the chemical structural formula is as follows:
characterization data: white solid, melting point: 63.0-66.0 ℃;1H NMR(400MHz,CDCl3)δ7.55-7.47(m,2H),7.36(d,J＝7.2Hz,1H),7.17(t,J＝8.0Hz,1H),1.40(s,9H)；13C NMR(100MHz,CDCl3)δ158.6,149.0,138.1,136.1,130.8,126.0,124.2,120.9,120.7,35.2,28.5。
the statements in this specification merely set forth a list of implementations of the inventive concept and the scope of the present invention should not be construed as limited to the particular forms set forth in the examples.
Claims (15)
1. A synthesis method of C-3 alkyl substituted coumarin derivative shown in formula (III) is characterized in that the coumarin derivative shown in formula (I) and formula (II) areNDissolving an alkanoyloxy phthalimide compound, a photocatalyst and protonic acid in an organic solvent, reacting for 3-36h at the temperature of 20-60 ℃ under the irradiation of visible light, and after the reaction is finished, carrying out post-treatment on a reaction system to obtain a C-3 alkyl substituted coumarin derivative target product shown in a formula (III); the reaction formula is as follows:
in the formulae (I) and (III), the substituent R1Is H, methyl, methoxy, fluorine, chlorine or bromine;
in the formulae (II) and (III), the substituent R2Is a linear or cyclic alkyl of C1-C8;
the photocatalyst is Ir (ppy)3；
The protonic acid is trifluoroacetic acid or trifluoromethanesulfonic acid.
2. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 1, wherein the C-3 alkyl substituted coumarin derivative is represented by formula (II)NThe ratio of the amount of the (E) -alkanoyloxy phthalimide compound to the amount of the coumarin derivative represented by the formula (I) is 1-4: 1.
3. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 2, wherein the C-3 alkyl substituted coumarin derivative is represented by formula (II)NThe ratio of the amount of the (E) -alkanoyloxy phthalimide compound to the amount of the coumarin derivative represented by the formula (I) is 1-2: 1.
4. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 1, wherein the ratio of the coumarin derivative represented by the formula (I) to the photocatalyst is 1: 0.01-0.1.
5. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 4, wherein the ratio of the coumarin derivative represented by the formula (I) to the photocatalyst is 1: 0.01-0.05.
6. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 1, wherein said protic acid is trifluoroacetic acid.
7. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 1, wherein the mass ratio of the protonic acid to the coumarin derivative represented by the formula (I) is 0.2-1: 1.
8. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 7, wherein the mass ratio of the protonic acid to the coumarin derivative represented by the formula (I) is 0.4-1: 1.
9. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 1, wherein the visible light is white light or blue light.
10. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 9, wherein said visible light is white light.
11. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 1, wherein the reaction temperature is 20-40 ℃, and the organic solvent is DMF or DMSO.
12. The method for synthesizing C-3 alkyl substituted coumarin derivatives as claimed in claim 11, wherein said organic solvent is DMSO.
13. The method for synthesizing the C-3 alkyl substituted coumarin derivative according to claim 1, wherein the post-treatment of the reaction system comprises: adding water and an organic extractant into a reaction system for extraction, separating liquid into an organic layer and a water layer, drying the organic layer by anhydrous sodium sulfate, removing the solvent by decompression concentration, separating the concentrated residue by column chromatography, collecting eluent containing a target product by taking a mixed solvent of petroleum ether and ethyl acetate as an eluent, and evaporating the solvent to obtain the target product of the C-3 alkyl substituted coumarin derivative shown in the formula (III).
14. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 13, wherein said organic extractant is dichloromethane or ethyl acetate; in the mixed solvent of the petroleum ether and the ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 8-30: 1.
15. The method for synthesizing C-3 alkyl substituted coumarin derivative according to claim 14, wherein said organic extractant is dichloromethane.
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