CN111285759B - Synthetic method of chalcone derivative - Google Patents
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- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
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Abstract
The invention provides a synthesis method of chalcone derivatives, which comprises the following steps: adding PPA and a solvent 1, 4-dioxane into a container, sequentially adding 98% concentrated sulfuric acid, substituted benzaldehyde and substituted acetophenone, and heating and stirring at 90 ℃ under the protection of nitrogen for reacting for 2 hours; separating and purifying after the reaction is finished to obtain the chalcone derivatives. The synthesis method provided by the invention has the advantages of low catalyst price, mild reaction conditions, simple and convenient operation and high yield, and provides a new method for synthesizing chalcone derivatives.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of chalcone derivatives.
Background
Chalcones are one of the most common simple scaffolds found in many naturally occurring compounds, and the biological activity of chalcone derivatives has been found to have clinical potential against various diseases, and the history of human application of chalcone derivatives dates back thousands of years to the treatment of many diseases, such as cancer, inflammation and diabetes, with plants and herbs. The compounds of the chalcone scaffold are also approved for clinical use. For example: metochalcone has been marketed as an anticholinergic, whereas saratine has previously been used as an antiulcer and mucosal protective drug. In addition, the chalcone compound can be combined with a plurality of receptors due to the flexibility of the structure of the chalcone compound, so that a plurality of chalcone compounds have biological activities such as enterobiasis resistance, allergy resistance, tumor resistance, oxygen free radical inhibition and elimination, bacteria resistance, virus resistance, ulcer resistance, spasmolysis and the like, so that the chalcone derivative has wide biological activity, and how to obtain the chalcone derivative efficiently is an object of efforts of chemists.
The most classical synthesis method for the synthesis of chalcone derivatives is the base or acid catalyzed Claisen-Schmidt condensation. Commonly used base catalysts are (a) sodium hydroxide (J.Nat.Prod.2014,77, 550-556; J.Nat.Prod.2015,78, 2481-2487; Synth.Commun.2003,33,3935-3941), (b) potassium hydroxide (Wiley-VCH: Weinheim, Germany,1981,285), (c) alkaline earth metal hydroxides (chem.Rec.2012,12,329-355), (d) lithium bis (trimethylsilyl) amide (Tetrahedron Lett.1999,40, 7095-7098). The acid catalyst includes (e) hydrogen chloride (J.Am.chem.Soc.1937,59, 809-) 811, (f) boron trifluoride (chem.Rec.2012,12, 329-) 355; Tetrahedron Lett.2007,48, 3177-) 3180, (g) aluminum trichloride (J.Am.chem.Soc.1937,59, 809-) 811), (h) titanium tetrachloride (Synthesis 1980,41-44), (i) p-toluenesulfonic acid (Contemp.chem.Ind.2012,41, 23-25). The synthesis of chalcone derivatives by (j) a grinding method (Synth. Commun.2009,39, 2789-. In addition to the classical condensation reaction, the cross-coupling method [ (m) Suzuki reaction (Tetrahedron Lett.2003,44, 5359-5363; Tetrahedron Lett.1999,40, 3057-3060; Tetrahedron Lett.1999,40, 3109-3112; org.Lett.2007,9,707-710), (n) Heck reaction (Eur.J.org.Chem.2004,2004, 2894-2898; Tetrahedron Lett.2003,44, 910-9109; J.Am.Chem.Soc.2010,132, 14596-14602; etc.), (o) Julian-Kocienski reaction (Tetrahedron 2010,66, 9445-9449; Angew.Chem., Int.2010, 2010,49, 2668-79), (p) Wittiki reaction (Tetrahedron 2010,66, 9445-9449; Tetrahedron J.19519, 22, 19545-45-2000; and the like derivatives (Fruegh.22, 1979-19, 1979, 17, 11, 1979-19-2000-82, and 22, 1979-17, 11, 1979-17, and 22, 82-17, respectively. The methods for preparing chalcone by a-q have certain limitations, and are shown in table 1.
Table 1 limitations of the reported methods for synthesizing chalcone derivatives
Therefore, the further development of a simple, efficient and mild reaction condition synthesis method of chalcone derivatives has certain significance.
Disclosure of Invention
The invention aims to provide a method for synthesizing chalcone derivatives by acid catalysis, which has the advantages of simple operation, short reaction time and high yield.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthesis method of chalcone derivatives is disclosed, wherein the structure of the chalcone derivatives is shown as the following general formula I:
wherein R is 1 Is any one of hydrogen, methyl and methoxy, R 2 Is any one of hydrogen, methyl, methoxy, fluorine, chlorine and bromine; r 1 At any one or two of ortho-, meta-and para-positions of the benzene ring, R 2 Is positioned at any one or two of ortho, meta and para positions of the benzene ring;
adding PPA and a solvent 1, 4-dioxane into a container, sequentially adding 98% concentrated sulfuric acid, substituted benzaldehyde and substituted acetophenone, and heating and stirring for reaction for 2h under the protection of nitrogen; separating and purifying after the reaction is finished to obtain chalcone derivatives;
the structural formula of the substituted benzaldehyde is as follows:
the structural formula of the substituted acetophenone is as follows:
the synthesis method of the chalcone derivative comprises the following steps: substituted acetophenone: PPA: the molar ratio of 98% concentrated sulfuric acid is 0.7: 1: 5: 20.
in the synthesis method of the chalcone derivative, the dosage of the solvent 1, 4-dioxane is 0.2-0.6mL/mmol PPA.
The chalcone derivative is synthesized by heating in an oil bath at 90 ℃.
In the synthesis method of the chalcone derivative, the separation and purification process after the reaction is finished comprises the following steps: 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 with silica gel column chromatography to obtain chalcone derivatives.
According to the synthesis method of the chalcone derivative, the silica gel column chromatography eluent is petroleum ether/ethyl acetate, and the volume ratio is 30-50: 1.
the synthesis reaction equation of the chalcone derivative is as follows:
compared with the prior art, the invention has the beneficial effects that:
the method for synthesizing chalcone derivatives by acid catalysis is provided, the catalysts are PPA and concentrated sulfuric acid, the price is low, and the catalytic effect is good. Polyphosphoric Acid (PPA) is used as a water loss agent, a cyclizing agent, and an acylating agent in organic synthesis, and is a catalyst or a solvent for reactions such as condensation, cyclization, rearrangement, and substitution. The method is based on the condition of acid catalysis, and the C ═ C double bond is constructed more quickly after polyphosphoric acid is added as a catalyst, so that the chalcone framework is obtained. The synthesis method has the advantages that the reaction is carried out at 90 ℃ under normal pressure, and the condition is mild; the reaction time is short and is only 2 hours; the operation is simple, the yield is up to more than 75%, the yield can be up to 96% according to different group raw materials, and a novel method is provided for the synthesis of chalcone derivatives.
In order to ensure the scientific and reasonable synthesis method of the chalcone derivatives, the inventor carries out corresponding research and screening through the following tests, and finally determines the technical scheme of the invention.
1. Reagent and apparatus
XT-4 type micro melting point tester, Beijing Taiguan instruments, Inc.;
INOVA 600MHz nuclear magnetic resonance tester (TMS internal standard), warian technologies, china ltd, usa;
HP1100 liquid chromatography-mass spectrometry combined instrument, Shanghai Analyzer factory;
polyphosphoric acid, carbofuran reagents ltd;
concentrated sulfuric acid, Chongqing Chuanjiang chemical reagent plant;
substituted benzaldehyde, substituted acetophenone, carbofuran reagents ltd;
thin layer chromatography silica gel plate, Qingdao ocean chemical plant.
2. Reaction condition optimization
Benzaldehyde (0.7mmol) and acetophenone (1.0mmol) are used as reaction substrates, PPA molar equivalent, concentrated sulfuric acid molar equivalent, reaction temperature, reaction time and solvent category are selected as reaction factors for investigation aiming at a reaction route, and the influence of each reaction factor on yield is designed and investigated, and the results are shown in Table 2. As can be seen from Table 2, the yield is highest when the molar equivalent of concentrated sulfuric acid is 20, and the yield is reduced after the equivalent is continuously increased; the PPA equivalent is the optimum yield at 5, and the yield is slightly reduced after the equivalent is increased; the optimal reaction time is 2h, the reaction is continued, and the yield is reduced; the reaction temperature is optimally 90 ℃. Therefore, the optimal reaction conditions are that the molar equivalent of the concentrated sulfuric acid is 20, the molar equivalent of the PPA is 5, the reaction time is 2 hours, and the reaction temperature is 90 ℃.
The solvent selects 1, 4-dioxane, absolute ethyl alcohol (EtOH), Tetrahydrofuran (THF), dimethyl sulfoxide (DMSO) and Dimethylformamide (DMF) under the optimal reaction condition as the objects to be investigated.
The yield is optimal when 1, 4-dioxane is used as a reaction solvent, the yield difference of different acid types used as catalysts is considered under the condition that other reaction conditions are fixed, and concentrated sulfuric acid is finally determined to be the optimal yield acid.
3. Test results
Through single factor experiments, the yield obtained by the reaction is the best when PPA is 5 times equivalent, concentrated sulfuric acid is 20 times equivalent, the reaction temperature is 90 ℃, the reaction time is 2 hours, and the solvent is 1, 4-dioxane; it can be seen that the yield is improved when the reaction temperature is increased, but the yield is decreased after the reaction is more than 90 ℃ considering that the boiling point of the solvent 1, 4-dioxane is 101 ℃.
Compared with the synthesis of chalcone derivatives under other acidic conditions, the method is used as a new development of the synthesis strategy system, is simple to operate and has ideal yield, and a new thought and method are provided for the synthesis of chalcone compounds under acidic conditions.
TABLE 2 Effect of various reaction factors on yield
The optimized reaction conditions are adopted to synthesize chalcone derivatives with different substituents, which are shown in the examples in detail.
Detailed Description
Example 1: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate (analytically pure) 5mmol and 1, 4-dioxane (analytically pure) 2mL into a round-bottom flask, and sequentially adding 20mmol of 98% concentrated sulfuric acid, 0.7mmol of benzaldehyde and p-methyl (p-CH) 3 ) Heating and stirring acetophenone 1mmol in oil bath at 90 ℃ under the protection of nitrogen for 2 hours; after the reaction, the mixture was extracted 3 times with 50ml of ethyl acetate to obtainWashing the organic layer with tap water and saturated sodium chloride solution in sequence, drying the washed organic layer with anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-1; the yield was 95%.
Nuclear magnetic resonance of chalcone derivatives (I-1) obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.02(m,2H),7.80(d,1H),7.58(s,1H),7.55(d,2H),7.51(m,7.4Hz,3H),7.23(d,2H),2.40(s,3H). 13 C NMR(151MHz,CDCl 3 )δ191.00,145.29,141.43,138.70,133.00,132.50,130.05,128.93,128.81,121.44,21.88.
example 2: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2-3mL as solvent into a flask, and sequentially adding 98% concentrated sulfuric acid 20mmol, benzaldehyde 0.7mmol, and 2, 4-chlorination (m, m-Cl) 2 ) 1mmol of acetophenone is heated and stirred at 90 ℃ under the protection of nitrogen for reaction for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing the organic layer by using distilled water and a saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 40: 1) to obtain chalcone derivative I-2; the yield was 75%.
Nuclear magnetic resonance of the chalcone derivatives (I-2) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.10(d,1H),8.01(m,2H),7.68(d,1H),7.60(t,1H),7.55–7.44(m,4H),7.30(d,1H). 13 C NMR(151MHz,CDCl 3 )δ190.24,139.46,137.90,136.60,136.20,133.21,131.98,130.27,128.84,128.74,128.63,127.69,125.15.
example 3: a synthesis method of chalcone derivatives comprises the following steps:
adding 5mmol of PPA polyphosphate and 2mL of 1, 4-dioxane as a solvent into a flask, sequentially adding 20mmol of 98% concentrated sulfuric acid, 0.7mmol of benzaldehyde and 1mmol of p-bromo (p-Br) acetophenone, and heating and stirring in an oil bath at 90 ℃ under the protection of nitrogen for reacting for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 30: 1) to obtain chalcone derivative I-3; the yield was 80%.
Nuclear magnetic resonance of the chalcone derivatives (I-3) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.18(d,1H),8.04–8.00(m,2H),7.75(dd,J＝7.1,2.3Hz,1H),7.59(t,J＝7.4Hz,1H),7.53–7.48(m,3H),7.45–7.42(m,1H),7.32(t,J＝5.3Hz,2H). 13 CNMR(151MHz,CDCl 3 )δ189.86,142.99,137.63,133.43,132.58,131.84,129.42,128.31,128.13,124.43,122.19.
example 4: a synthesis method of chalcone derivatives comprises the following steps:
adding 5mmol of PPA polyphosphate and 2mL of 1, 4-dioxane as a solvent into a flask, sequentially adding 20mmol of 98% concentrated sulfuric acid, 0.7mmol of benzaldehyde and 1mmol of acetophenone, and heating and stirring in an oil bath at 90 ℃ under the protection of nitrogen for reacting for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-4; the yield was 96%.
Nuclear magnetic resonance of the chalcone derivatives (I-4) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.05–8.00(m,2H),7.82(d,1H),7.65(dd,3.0Hz,2H),7.55(m,7.4Hz,4H),7.43(dd,3H). 13 C NMR(151MHz,CDCl 3 )δ190.93,145.21,138.57,135.24,133.14,130.90,129.32,128.98,128.86,128.80,122.46.
example 5: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding concentrated sulfuric acid 20mmol of 98%, benzaldehyde 0.7mmol and o-methyl (o-CH) 3 ) Heating and stirring acetophenone 1mmol in oil bath at 90 ℃ under the protection of nitrogen for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing by using water and saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, and separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-5; the yield was 90%.
Nuclear magnetic resonance of chalcone derivatives (I-5) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.07(d,2H),7.83(d,1H),7.68–7.66(m,2H),7.58(d,1H),7.46–7.43(m,3H),7.01(d,2H),3.91(s,3H). 13 C NMR(151MHz,CDCl 3 )δ189.07,163.78,144.31,135.43,131.44,131.16,130.67,129.26,128.70,122.24,114.20,55.84.
example 6: a synthesis method of chalcone derivatives comprises the following steps:
adding 5mmol of PPA polyphosphate and 2mL of 1, 4-dioxane as a solvent into a flask, sequentially adding 20mmol of 98% concentrated sulfuric acid, 0.7mmol of benzaldehyde and 1mmol of o-chloro (o-Cl) acetophenone, and heating and stirring in an oil bath at 90 ℃ under the protection of nitrogen for reacting for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 40: 1) to obtain chalcone derivative I-6; the yield was 82%.
Nuclear magnetic resonance of the chalcone derivatives (I-6) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.18(d,1H),8.04–8.00(m,2H),7.75(dd,1H),7.59(t,1H),7.53–7.46(m,3H),7.44(dd,1H),7.33–7.30(m,2H). 13 C NMR(151MHz,CDCl 3 )δ190.32,140.51,137.81,135.38,133.14,132.84,131.08,130.19,128.56,128.52,127.68,126.99,124.69.
example 7: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding concentrated sulfuric acid 20mmol of 98%, benzaldehyde 0.7mmol and 1-methyl-5-fluorine (o-CH) 3 o-F) acetophenone 1mmol, and the mixture is heated and stirred in an oil bath at 90 ℃ under the protection of nitrogen for reaction for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 40: 1) to obtain chalcone derivative I-7; the yield was 86%.
Nuclear magnetic resonance of the chalcone derivatives (I-7) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.06–8.02(m,2H),7.91(d,1H),7.73(d,1H),7.59(t,1H),7.51(t,2H),7.23(d,1H),7.03(d,1H),7.01–6.97(m,1H),2.50(s,3H). 13 C NMR(151MHz,CDCl 3 )δ190.77,141.01,140.93,138.19,136.00,133.04,130.66,130.59,128.69,127.30,127.21,126.56,122.25,114.08,113.93,20.55.
example 8: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding 20mmol of 98% concentrated sulfuric acid and p-methyl (p-CH) 3 ) 0.7mmol of benzaldehyde and 1mmol of acetophenone are heated and stirred in an oil bath at 90 ℃ under the protection of nitrogen for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-8; the yield was 82%.
Prepared byNuclear magnetic resonance of keton derivative (I-8) (I-8) 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ7.95(m,2H),7.81(d,1H),7.66–7.63(m,2H),7.54(d,1H),7.44–7.40(m,3H),7.31(d,2H),2.44(s,3H). 13 C NMR(151MHz,CDCl 3 )δ190.15,144.51,135.76,135.12,130.54,129.46,129.06,128.78,128.53,122.22,21.80.
example 9: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding 20mmol of 98% concentrated sulfuric acid and p-methyl (p-CH) 3 ) Benzaldehyde 0.7mmol, p-methyl (p-CH) 3 ) Heating and stirring acetophenone 1mmol in oil bath at 90 ℃ under the protection of nitrogen for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of ethyl acetate, taking an organic layer, washing by using water and saturated sodium chloride solution in sequence, drying the washed organic layer by using anhydrous sodium sulfate, and filtering; concentrating the obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-9; the yield was 91%.
Nuclear magnetic resonance of the chalcone derivatives (I-9) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ7.94(m,2H),7.79(d,1H),7.54(d,2H),7.50(d,1H),7.30(d,2H),7.22(d,2H),2.44(s,3H),2.39(s,3H). 13 C NMR(151MHz,CDCl 3 )δ190.44,144.81,143.82,141.26,136.10,132.60,130.01,129.63,128.95,128.76,121.43,21.99,21.85.
example 10: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding 20mmol of 98% concentrated sulfuric acid and p-methyl (p-CH) 3 ) Benzaldehyde 0.7mmol, o-methoxy (o-OCH) 3 ) Heating and stirring acetophenone 1mmol in oil bath at 90 ℃ under the protection of nitrogen for 2 hours; extracting with ethyl acetate 50ml for 3 times after reaction, collecting organic layer, washing with water and saturated sodium chloride solution, drying the washed organic layer with anhydrous sodium sulfate, and filtering(ii) a Concentrating the obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-10; the yield was 87%.
Nuclear magnetic resonance of the chalcone derivatives (I-10) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.12(d,1H),7.94(d,2H),7.63(t,2H),7.37(t,1H),7.30(d,2H),6.99(t,1H),6.94(d,1H),3.91(s,3H),2.43(s,3H). 13 C NMR(151MHz,CDCl 3 )δ190.76,158.89,143.45,140.07,136.06,131.75,129.37,129.29,128.81,124.18,123.04,120.85,111.35,77.37,77.16,76.95,55.66,21.79.
example 11: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane 2mL of solvent into a flask, and sequentially adding 20mmol of 98% concentrated sulfuric acid and p-methyl (p-CH) 3 ) 0.7mmol of benzaldehyde, 1mmol of o-chloro (o-Cl) acetophenone and the mixture are heated and stirred in an oil bath at 90 ℃ under the protection of nitrogen for reaction for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-11; the yield was 88%.
Nuclear magnetic resonance of the chalcone derivatives (I-11) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.17(d,1H),7.93(d,2H),7.75–7.73(m,1H),7.48(d,1H),7.44–7.41(m,1H),7.32(s,1H),7.31(d,2H),7.29(s,1H),2.43(s,3H). 13 C NMR(151MHz,CDCl 3 )δ190.25,144.21,140.53,135.80,135.72,133.73,131.43,130.64,129.75,129.15,128.14,127.44,125.21,22.07.
example 12: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and 1, 4-dioxane solvent 2mL into a flask, and sequentially adding 98% concentrated sulfuric acid 20mmol, o-methoxy (o-OCH) 3 ) 0.7mmol of benzaldehyde, 1mmol of o-chloro (o-Cl) acetophenone and the mixture are heated and stirred in an oil bath at 90 ℃ under the protection of nitrogen for reaction for 2 hours; after the reaction is finished, extracting for 3 times by using 50ml of 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 obtained filtrate under reduced pressure, separating and purifying the concentrated residue by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 50: 1) to obtain chalcone derivative I-12; the yield was 86%.
Nuclear magnetic resonance of the chalcone derivatives (I-12) thus obtained 1 H NMR and 13 c NMR) the data were: 1 H NMR(600MHz,CDCl 3 )δ8.16(d,1H),8.03(d,2H),7.76–7.73(m,1H),7.49(d,1H),7.45–7.42(m,1H),7.31(t,2H),6.98(d,2H),3.89(s,3H). 13 C NMR(151MHz,CDCl 3 )δ189.60,164.52,140.75,136.35,134.45,131.81,131.25,128.74,128.01,125.71,114.87,56.48.
TABLE 3 dosage ratio of each substance in examples 1 to 12
Example 13: a synthesis method of chalcone derivatives comprises the following steps:
adding 5mmol of PPA polyphosphate and 1-2mL of a solvent 1, 4-dioxane into a flask, sequentially adding 20mmol of 98% concentrated sulfuric acid, 0.7mmol of benzaldehyde and 1mmol of o-chloro (o-Cl) acetophenone, and heating and stirring for reacting for 2 hours under the protection of nitrogen; after the reaction is finished, separating and purifying to obtain the chalcone derivative I-6.
Example 14: a synthesis method of chalcone derivatives comprises the following steps:
adding PPA polyphosphate 5mmol and a proper amount of 1, 4-dioxane as solvent into a container, and sequentially adding 20mmol of 98% concentrated sulfuric acid and p-methyl (p-CH) 3 ) Benzaldehyde 0.7mmol, o-methoxy (o-OCH) 3 ) 1mmol of acetophenone is heated and stirred at 90 ℃ under the protection of nitrogen for reaction for 2 hours; separating and purifying after the reaction is finished to obtain the chalcone derivative I-10.
The structural formulas of the chalcone derivatives I-1 to I-12 correspond to the following numbers:
Claims (4)
1. a synthesis method of chalcone derivatives is disclosed, wherein the structure of the chalcone derivatives is shown as the following general formula I:
Ⅰ
wherein R is 1 Is any one of hydrogen, methyl and methoxy, R 2 Is any one of hydrogen, methyl, methoxy, fluorine, chlorine and bromine; r 1 At any one or two of ortho-, meta-and para-positions of the benzene ring, R 2 Is positioned at any one or two of ortho, meta and para positions of a benzene ring, and is characterized in that:
adding PPA and a solvent 1, 4-dioxane into a container, sequentially adding 98% concentrated sulfuric acid, substituted benzaldehyde and substituted acetophenone, and heating and stirring in a 90 ℃ oil bath under the protection of nitrogen for reaction for 2 hours; separating and purifying after the reaction is finished to obtain chalcone derivatives; the substituted benzaldehyde is as follows: substituted acetophenone: PPA: the molar ratio of 98% concentrated sulfuric acid is 0.7: 1: 5: 20;
the structural formula of the substituted benzaldehyde is as follows:
the structural formula of the substituted acetophenone is as follows:
2. the method for synthesizing chalcone derivatives according to claim 1, wherein: the dosage of the solvent 1, 4-dioxane is 0.2-0.6mL/mmol PPA.
3. The method for synthesizing chalcone derivatives 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 with silica gel column chromatography to obtain chalcone derivatives.
4. The method for synthesizing chalcone derivatives according to claim 3, wherein: the silica gel column chromatography eluent is petroleum ether/ethyl acetate, and the volume ratio is 30-50: 1.
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