Synthesis method of carbonyl substituted benzodihydropyran and benzodihydropyran compound
阅读说明：本技术 羰基取代的苯并二氢呋喃、苯并二氢吡喃化合物的合成方法 (Synthesis method of carbonyl substituted benzodihydropyran and benzodihydropyran compound ) 是由 杨礼寿 杨小生 王恩花 杨倩 彭梅 李齐激 王瑜 罗忠圣 李良群 邓廷飞 曹家辅 于 2021-01-07 设计创作，主要内容包括：本发明提供了羰基取代苯并二氢呋喃及羰基取代苯并二氢吡喃化合物的合成方法,具体为：耐压反应瓶中加入多聚磷酸PPA、溶剂N,N-二甲基甲酰胺DMF和羰基取代邻烯丙基/羰基取代异戊烯基苯酚,加热搅拌反应2-10h；反应结束后分离纯化,即得羰基取代苯并二氢呋喃/羰基取代苯并二氢吡喃化合物。本发明合成方法为首次公开,其反应时间短、催化剂PPA廉价易得、底物普适性好且产物产率较好,不但为羰基取代苯并二氢呋喃及羰基取代苯并二氢吡喃化合物的合成提供了一种新方法,也为产品规模化生产及提高生产效率奠定了基础。(The invention provides a synthesis method of carbonyl substituted chroman and a carbonyl substituted chroman compound, which comprises the following steps: PPA, N-dimethylformamide DMF and carbonyl substituted o-allyl/carbonyl substituted isopentenyl phenol are added into a pressure-resistant reaction bottle, and the mixture is heated and stirred to react for 2 to 10 hours; and separating and purifying after the reaction is finished to obtain the carbonyl substituted chroman/carbonyl substituted chroman compound. The synthetic method disclosed by the invention is disclosed for the first time, the reaction time is short, the PPA catalyst is cheap and easy to obtain, the substrate universality is good, and the product yield is good, so that a new method is provided for the synthesis of the carbonyl substituted chroman and the carbonyl substituted chroman compound, and a foundation is laid for the large-scale production of the product and the improvement of the production efficiency.)
1. the carbonyl substituted chroman and the carbonyl substituted chroman compound have the following structures shown as formulas II 1-11:
the method is characterized by comprising the following steps:
adding PPA, N-dimethylformamide DMF and carbonyl substituted o-allyl/carbonyl substituted isopentenyl phenol into a pressure-resistant reaction bottle, and heating and stirring for reacting for 2-10 h; separating and purifying after the reaction is finished to obtain a carbonyl substituted chroman/carbonyl substituted chroman compound;
the structures of the carbonyl-substituted o-allyl and carbonyl-substituted isopentenyl phenol are shown as the following formulas I1-11:
2. the method for synthesizing carbonyl-substituted chroman and carbonyl-substituted chroman compounds according to claim 1, wherein: the molar ratio of the carbonyl-substituted o-allyl/carbonyl-substituted isopentenyl phenol to the PPA polyphosphate is 1: 5 to 30.
3. The method for synthesizing carbonyl-substituted chroman and carbonyl-substituted chroman compounds according to claim 1, wherein: the dosage of the solvent DMF is 1.5mL/mmol of carbonyl-substituted o-allyl/carbonyl-substituted isopentenyl phenol.
4. The method for synthesizing carbonyl-substituted chroman and carbonyl-substituted chroman compounds according to claim 1, wherein: the heating is carried out by oil bath heating at 90-160 ℃.
5. The method for synthesizing carbonyl-substituted chroman and carbonyl-substituted chroman compounds according to claim 1, wherein: the separation and purification process after the reaction is as follows: extracting a substance obtained after the reaction is finished for 2-3 times by using ethyl acetate, taking an organic layer, washing the organic layer by using water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the filtrate under reduced pressure, and separating and purifying the concentrated residue by silica gel column chromatography to obtain carbonyl substituted chroman/carbonyl substituted chroman compound.
6. The method for synthesizing carbonyl-substituted chroman and carbonyl-substituted chroman compounds according to claim 5, wherein: the silica gel column chromatography elution is carried outThe agent is petroleum ether and ethyl acetate, VPetroleum ether/VEthyl acetate＝2～5：1。
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of carbonyl-substituted chroman and carbonyl-substituted chroman compounds.
Background
The chroman and chroman system exists in a large number of bioactive compounds and has remarkable biological activity, such as anti-genetic toxicity, anti-proliferation, anti-cancer, anti-inflammation and the like, and the most common reported method for preparing the chroman and chroman compounds is an intra-molecular cyclization method of o-allyl/isopentenylphenol. The carbonyl substituted chromans and chromans also have a wide range of biological activities, such as anti-cancer, anti-proliferative and inhibitory activity on D-amino acid oxidases. The synthesis method of carbonyl substituted benzodihydro furan and benzodihydropyran compounds mainly uses I2(Heterocycles.1995,41:219-223)、H2SO4(Lett Org Chem.2009,6:29-36；Synthesis.2010,21:3745-3754；Eur J Org Chem.2015,10:2297-2302)、HCl(Chem Pharm Bull.1981,29:3033-3036)、p-TsOH(Can J Chem.1970,48:680-684；RSC Adv.2018,8:41377-41388)、TFA(Molecules.2018,23:776-792)、AlCl3(Molecules.2018,23:776-792)、ZrCl4(Synth Commun.2004,34:3091-3097) and BF3/Et2O (Tetrahedron Lett.2007,48: 7628-. However, these synthetic methods have limitations such as low yield, long reaction time, and no discussion of substrate universality, and the specific limitations are shown in table 1.
Table 1 reported limitations of the synthesis method of carbonyl substituted chromans and chromans
Disclosure of Invention
The invention aims to provide a synthesis method of carbonyl-substituted chroman and a carbonyl-substituted chroman compound, which has the advantages of short reaction time, simple operation, no need of nitrogen protection, cheap and easily available catalyst PPA and good substrate universality.
In order to achieve the purpose, the invention adopts the following technical scheme:
the carbonyl substituted chroman and the carbonyl substituted chroman compound have the following structures shown as formulas II 1-11:
the synthesis method comprises the following steps:
adding PPA, N-dimethylformamide DMF and carbonyl substituted o-allyl/carbonyl substituted isopentenyl phenol into a pressure-resistant reaction bottle, and heating and stirring for reacting for 2-10 h; separating and purifying after the reaction is finished to obtain a carbonyl substituted chroman/carbonyl substituted chroman compound; the pressure-resistant reaction bottle can effectively avoid solvent volatilization;
the structures of the carbonyl-substituted o-allyl and carbonyl-substituted isopentenyl phenol are shown as the following formulas I1-11:
according to the synthesis method of the carbonyl-substituted chroman and the carbonyl-substituted chroman compound, the molar ratio of the carbonyl-substituted o-allyl/carbonyl-substituted isopentenyl phenol to the PPA polyphosphate is 1: 5 to 30.
According to the synthesis method of the carbonyl-substituted chroman and the carbonyl-substituted chroman compound, the dosage of the DMF solvent is 1.5mL/mmol of the carbonyl-substituted o-allyl/carbonyl-substituted isopentenyl phenol.
The synthesis method of the carbonyl-substituted chroman and the carbonyl-substituted chroman compound is characterized in that the heating is carried out in an oil bath at 90-160 ℃.
According to the synthesis method of the carbonyl-substituted chroman and the carbonyl-substituted chroman compound, the separation and purification process after the reaction is finished is as follows: extracting a substance obtained after the reaction is finished for 2-3 times by using ethyl acetate, taking an organic layer, washing the organic layer by using water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the filtrate under reduced pressure, and separating and purifying the concentrated residue by silica gel column chromatography to obtain carbonyl substituted chroman/carbonyl substituted chroman compound.
The eluent of silica gel column chromatography is petroleum ether and ethyl acetate, VPetroleum ether/VEthyl acetate＝2～5：1。
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a synthesis method of carbonyl substituted chroman and carbonyl substituted chroman compounds, and discloses a method for synthesizing carbonyl substituted chroman/carbonyl substituted chroman compounds by using PPA (PPA) polyphosphate as a catalyst to catalyze intramolecular cyclization of carbonyl substituted o-allyl/carbonyl substituted isopentenylphenol. The synthesis method disclosed by the invention has the advantages that the reaction time is short (2-10h), the catalyst PPA is cheap and easy to obtain, and the production period and the cost are greatly reduced; the reaction substrate has good universality, the average yield of the product is higher and can reach 91 percent at most, a new method is provided for the synthesis of the carbonyl substituted chroman and the carbonyl substituted chroman compound, and a foundation is laid for the large-scale production of the product and the improvement of the production efficiency.
In order to ensure that the synthesis method of the carbonyl-substituted chroman and chroman compounds is scientific and reasonable, the inventor carries out corresponding research and screening through the following tests to finally determine the technical scheme of the invention.
3-allyl-2-hydroxybenzaldehyde (I1) (0.2mmol) was used as a reaction substrate, and the reaction was carried out in an oil bath at 130 ℃ with stirring for 10 hours using a solvent amount of 0.3 mL. PPA molar equivalent and solvent category are selected as reaction factors to investigate the influence of each reaction factor on yield, and the results are shown in Table 1.
TABLE 1 Effect of various reaction factors on yield
As can be seen from Table 1, the optimum reaction conditions were PPA molar equivalent of 5 and DMF as the reaction solvent. When the reaction substrates I2-I11 are used for synthesis verification according to the optimal conditions, the yield is higher when the PPA molar equivalent is increased to 20 and 30 by a few substrates, so that the PPA molar equivalent is finally selected to be 5-30.
Carbonyl substituted chroman/carbonyl substituted chroman compounds with different substituents are synthesized by using the optimized PPA molar equivalent and the reaction solvent DMF, and are detailed in examples 1-11.
Detailed Description
To further confirm the rationality of the preparation method and the structural accuracy of the synthesized compound, the carbonyl-substituted chroman/carbonyl-substituted chroman compounds prepared in examples 1 to 11 were subjected to nuclear magnetic resonance using nuclear magnetic resonance (1H NMR and13c NMR).
Example 1: a method for synthesizing carbonyl substituted benzodihydrofuran compound comprises the following steps:
adding 1mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of raw material I1, and stirring in an oil bath at 130 ℃ for reaction for 10 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateAnd (5) separating and purifying the obtained product to obtain the carbonyl substituted dihydrobenzofuran compound II 1 with the yield of 81%.
Nuclear magnetic resonance of the prepared carbonyl-substituted benzodihydrofuran compound (II 1) (II 1)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ10.23(s,1H),7.59(d,J＝7.8Hz,1H),7.38(dd,J＝7.2,1.2Hz,1H),6.92(t,J＝7.5Hz,1H),5.12(ddq,J＝12.7,8.8,6.3Hz,1H),3.36(dd,J＝15.6,8.9Hz,1H),2.85(dd,J＝15.6,7.4Hz,1H),1.55(d,J＝6.3Hz,3H).13C NMR(151MHz,CDCl3)δ189.00,161.97,130.93,129.53,126.99,120.36,119.51,81.72,36.01,21.83.
example 2: a method for synthesizing carbonyl substituted benzodihydrofuran compound comprises the following steps:
adding 1mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of raw material I2, and stirring in an oil bath at 150 ℃ for reacting for 6 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparation and purification are carried out according to the ratio of 5:1), and the carbonyl substituted dihydrobenzofuran compound II 2 is obtained with the yield of 52%.
Nuclear magnetic resonance of the prepared carbonyl-substituted benzodihydrofuran compound (II 2) ((1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ9.82(s,1H),7.36(s,1H),7.34(s,1H),5.19–5.12(m,1H),3.96(s,3H),3.43(dd,J＝15.4,9.0Hz,1H),2.93(dd,J＝15.4,7.8Hz,1H),1.58(d,J＝6.3Hz,3H).13C NMR(151MHz,CDCl3)δ190.63,153.85,145.00,130.96,128.47,121.76,111.11,82.25,56.03,36.75,21.79.
example 3: a method for synthesizing carbonyl substituted benzodihydrofuran compound comprises the following steps:
adding 4mmol of PPA, 0.3mL of DMF solvent and 0.2mmol of the raw material I3 into a 5mL pressure-resistant reaction bottle, and stirring in an oil bath at 90 ℃ for reaction for 10 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the obtained product at a ratio of 4:1) to obtain the carbonyl substituted dihydrobenzofuran compound II 3 with the yield of 78%.
Nuclear magnetic resonance of the prepared carbonyl-substituted benzodihydrofuran compound (II 3) (II 3)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ7.84(s,1H),7.82(d,J＝8.4,1.8Hz,1H),6.79(d,J＝8.4Hz,1H),5.05(m,J＝8.8,7.3,6.4Hz,1H),3.38(dd,J＝15.5,8.9Hz,1H),2.87(dd,J＝15.5,7.4Hz,1H),2.56(s,3H),1.51(d,J＝6.3Hz,3H).13C NMR(151MHz,CDCl3)δ196.72,163.85,130.56,130.46,127.76,125.63,108.92,81.04,36.37,26.40,21.79.
example 4: a method for synthesizing carbonyl substituted benzodihydrofuran compound comprises the following steps:
adding 4mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of raw material I4, and stirring in an oil bath at 90 ℃ for reaction for 10 hours; after the reaction, ethyl acetate was extracted 3 times, the organic layer was washed with water and saturated sodium chloride solution in this order, and thenThe washed organic layer was dried over anhydrous sodium sulfate, filtered, and the residue obtained by concentrating the filtrate under reduced pressure was subjected to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the obtained product by the ratio of 3:1) to obtain the carbonyl substituted dihydrobenzofuran compound II 4 with the yield of 71%.
Nuclear magnetic resonance of the prepared carbonyl-substituted benzodihydrofuran compound (II 4) (II)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ7.69(d,J＝8.7Hz,1H),6.40(d,J＝8.7Hz,1H),5.16–5.10(m,1H),3.32(dd,J＝15.2,9.0Hz,1H),2.79(dd,J＝15.2,7.2Hz,1H),2.60(s,3H),1.54(d,J＝6.3Hz,3H).13C NMR(151MHz,CDCl3)δ196.54,162.52,157.21,130.52,114.76,113.15,108.68,81.44,33.31,30.71,22.07.
example 5: a method for synthesizing carbonyl substituted benzodihydrofuran compound comprises the following steps:
adding PPA 6mmol, DMF 0.3mL and 0.2mmol of raw material I5 into a 5mL pressure-resistant reaction bottle, and stirring in an oil bath at 160 ℃ for reaction for 10 h; extracting with ethyl acetate for 2 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the obtained product by the ratio of 5:1) to obtain the carbonyl substituted dihydrobenzofuran compound II 5 with the yield of 90 percent.
Nuclear magnetic resonance of the prepared carbonyl-substituted benzodihydrofuran compound (II 5) (II 5)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ12.82(s,1H),7.90(s,1H),7.79–7.77(m,2H),7.68–7.65(m,2H),7.56(td,J＝7.5,1.2Hz,2H),7.49–7.43(m,4H),5.18(dp,J＝9.2,6.4Hz,1H),3.42(dd,J＝15.6,9.3Hz,1H),2.89(dd,J＝15.6,6.7Hz,1H),1.49(d,J＝6.3Hz,3H).13C NMR(151MHz,CDCl3)δ200.35,192.81,165.50,163.27,139.19,138.08,137.81,132.53,131.95,129.68,128.97,128.43,128.03,114.59,114.34,113.82,83.41,32.89,21.96.
example 6: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of raw material I6, and stirring in an oil bath at 110 ℃ for reaction for 2 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the product by the ratio of 3:1) to obtain the carbonyl substituted chroman compound II 6 with the yield of 80 percent.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 6) (II 6)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ13.09(s,1H),7.85(d,J＝15.4Hz,1H),7.64(s,1H),7.61(d,J＝8.5Hz,2H),7.48(d,J＝15.4Hz,1H),6.91(d,J＝8.6Hz,2H),6.39(s,1H),5.38(s,1H),2.80(t,J＝6.7Hz,2H),1.87(t,J＝6.7Hz,2H),1.39(s,6H).13C NMR(151MHz,CDCl3)δ191.76,164.13,161.38,157.90,143.76,131.04,130.53,127.90,118.18,115.98,114.25,112.63,104.93,75.94,32.80,26.99,21.83.
example 7: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA, 0.3mL of DMF solvent and 0.2mmol of the raw material I7 into a 5mL pressure-resistant reaction bottle, and stirring in an oil bath at 110 ℃ for reaction for 2 h; extracting with ethyl acetate for 2 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the product by the ratio of 3:1) to obtain the carbonyl substituted chroman compound II 7 with the yield of 77 percent.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 7) (II 7)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ14.84(s,1H),7.85(d,J＝15.6Hz,1H),7.78(d,J＝15.6Hz,1H),7.53(d,J＝8.6Hz,2H),6.89(d,J＝8.6Hz,2H),5.90(s,1H),5.73(s,1H),3.90(s,3H),2.65(t,J＝6.8Hz,2H),1.83(t,J＝6.8Hz,2H),1.38(s,6H).13C NMR(151MHz,CDCl3)δ192.59,165.55,160.75,160.73,157.61,142.02,130.29,128.48,125.39,115.88,105.52,102.03,91.78,76.21,55.70,32.16,26.75,16.12.
example 8: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of the raw material I8, and stirring in an oil bath at 130 ℃ for reaction for 2 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetate2:1) to obtain the carbonyl substituted chroman compound II 8 with the yield of 81 percent.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 8) (II 8)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ11.51(s,1H),8.21(d,J＝8.9Hz,2H),7.06(d,J＝9.0Hz,2H),6.71(s,1H),6.28(s,1H),3.92(s,3H),2.93(t,J＝6.7Hz,2H),1.92(t,J＝6.7Hz,2H),1.41(s,6H).13C NMR(151MHz,CDCl3)δ175.18,160.99,160.37,158.38,153.91,144.97,135.78,129.16,123.65,114.14,103.54,99.83,76.12,55.43,31.71,26.65,16.25.
example 9: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA, 0.3mL of DMF solvent and 0.2mmol of raw material I9 into a 5mL pressure-resistant reaction bottle, and stirring in an oil bath at 110 ℃ for reaction for 4 hours; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetateSeparating and purifying the product by the ratio of 3:1) to obtain the carbonyl substituted chroman compound II 9 with the yield of 69 percent.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 9) (II)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ11.80(s,1H),7.20(dd,J＝8.4,2.0Hz,1H),7.16(s,1H),6.85(d,J＝8.4Hz,1H),5.99(s,1H),5.34(dd,J＝13.3,2.8Hz,1H),3.08(dd,J＝17.0,13.3Hz,1H),2.83(t,J＝6.7Hz,2H),2.79(dd,J＝17.0,2.9Hz,1H),2.66–2.55(m,2H),1.85(t,J＝6.7Hz,2H),1.82–1.73(m,2H),1.38(s,6H),1.37(s,3H),1.35(s,3H).13C NMR(151MHz,CDCl3)δ196.12,162.99,161.45,160.04,154.47,129.72,127.47,125.41,121.12,117.56,102.64,100.81,97.41,78.99,76.12,74.58,43.19,32.66,31.91,27.16,26.94,22.57,16.36.
example 10: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA, 0.3mL of DMF solvent and 0.2mmol of raw material I10 into a 5mL pressure-resistant reaction bottle, and stirring in an oil bath at 130 ℃ for reaction for 2 h; extracting with ethyl acetate for 3 times after reaction, sequentially washing organic layer with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, and subjecting the residue to silica gel column chromatography (V)Petroleum ether/VEthyl acetate2:1) to obtain carbonyl substituted chroman compound II 10 with the yield of 91%.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 10) (II 10)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ13.74(s,1H),6.84(s,1H),6.37(s,1H),6.25(s,1H),5.30(t,J＝6.4Hz,1H),4.12(d,J＝6.3Hz,2H),3.83(s,3H),2.73(t,J＝6.8Hz,2H),1.87–1.84(m,5H),1.71(s,3H),1.39(s,6H).13C NMR(151MHz,CDCl3)δ182.04,160.73,160.62,155.89,154.72,154.45,142.40,136.94,132.08,123.27,112.15,103.78,102.87,101.62,94.02,76.04,62.03,31.89,26.75,26.55,25.83,18.22.
example 11: a method for synthesizing carbonyl substituted chroman compounds comprises the following steps:
adding 1mmol of PPA and 0.3mL of DMF (dimethyl formamide) solvent into a 5mL pressure-resistant reaction bottle, adding 0.2mmol of raw material I11, and stirring in an oil bath at 130 ℃ for reaction for 2 hours; after the reaction, ethyl acetate was extracted 3 times, the organic layer was washed with water and a saturated sodium chloride solution in this order, and the washed organic layer was dried over anhydrous sodium sulfateThe organic layer was filtered, and the residue obtained after concentrating the filtrate under reduced pressure was subjected to silica gel column chromatography (V)Petroleum ether/VEthyl acetate2:1) to obtain the carbonyl substituted chroman compound II 11 with 89 percent of yield.
Nuclear magnetic resonance of the obtained carbonyl-substituted chroman compound (II 11) (II 11)1H NMR and13c NMR) the data were:1H NMR(600MHz,CDCl3)δ13.76(s,1H),6.82(s,1H),6.41(s,1H),6.27(s,1H),3.53(t,J＝6.8Hz,2H),2.74(t,J＝6.8Hz,2H),1.91(t,J＝6.8Hz,2H),1.86(t,J＝6.8Hz,2H),1.41(s,6H),1.39(s,6H).13C NMR(151MHz,CDCl3)δ182.67,160.51,160.44,154.93,153.27,151.54,137.79,121.33,111.22,103.53,103.03,100.50,93.99,75.94,75.51,32.89,31.92,26.77,26.49,22.37,16.08.
the structural formulas of the carbonyl substituted chroman/carbonyl substituted chroman compounds II 1-11 correspond to the following numbers: