CN111995605A - Chrysin cinnamate or its derivative and its preparation method - Google Patents
Chrysin cinnamate or its derivative and its preparation method Download PDFInfo
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Abstract
The invention discloses chrysin cinnamate or a derivative thereof and a preparation method thereof, belonging to the field of organic synthesis. The invention carries out Steglich esterification reaction on chrysin and cinnamic acid or derivatives thereof in an organic solvent under the action of a condensing agent and a catalyst to prepare the chrysin cinnamate or the derivatives thereof, has simple method, easy industrial production and high yield of target products of more than 40 percent, and the obtained chrysin cinnamate or the derivatives thereof have the characteristics of chrysin and cinnamic acid or the derivatives thereof, thereby providing a compound source for biological activity screening.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to chrysin cinnamate or a derivative thereof and a preparation method thereof.
Background
The synthesis of new molecules with potential biological activity by reacting two or more molecules with biological activity is an important strategy for constructing new compounds[1-2]. Chrysin is a natural polyphenol flavone compound with wide pharmacological activity extracted from oroxylum indicum of purple Weividae[3]It is widely found in honey and beeswax, and has antioxidant effectMultiple biological activities of dissolving, resisting virus, reducing blood sugar, resisting anxiety, etc[4-8]However, it also has the disadvantages of low solubility and poor bioavailability[8-9]. Cinnamic acid is a compound extracted from cortex Cinnamomi[10]The derivative of the compound has various biological activities of oxidation resistance, tumor resistance, bacteriostasis and the like[11-14]The research finds that the biological activity of various cinnamic acid derivatives is higher than that of the prototype drug[15]. Therefore, a series of novel compounds with diversity characteristics are synthesized by reacting chrysin and cinnamic acid derivatives, and a compound source is provided for biological activity screening.
Disclosure of Invention
In order to solve the defects and shortcomings of the prior art, the invention aims to provide chrysin cinnamate or derivatives thereof and a preparation method thereof.
In order to achieve the above objects, in a first aspect, the present invention provides a method for preparing chrysin cinnamate or a derivative thereof, comprising the steps of: performing Steglich esterification reaction on chrysin (with a structure shown in a formula (1)) and a compound shown in a structural formula (2) in an organic solvent under the action of a condensing agent and a catalyst to obtain chrysin cinnamate or a derivative thereof, wherein the structural formula of the chrysin cinnamate or the derivative thereof is shown in a formula (3);
each R is independently halogen, nitro, straight or branched chain alkyl, or straight or branched chain alkoxy, or two adjacent R are linked together to form-O (CH)2)pO-; n is an integer of 0 to 5; p is an integer of 1 or more.
The preparation method can prepare the chrysin cinnamate or the derivative thereof through a one-step method, not only has simple method and high yield of the target product of more than 40 percent, is easy for industrial production, but also has the characteristics of chrysin and cinnamic acid or the derivative thereof, and provides a compound source for bioactive screening.
As a preferred embodiment of the production method of the present invention, said n is 0, 1 or 2.
As a preferred embodiment of the preparation method of the present invention, said n is 1, and said R is 2-CH3-、3-CH3-、4-CH3-、2-Cl、3-Cl、4-Cl、2-Br、3-Br、4-Br、2-F、3-F、4-F、2-NO2-、3-NO2-、4-NO2-、2-OCH3、3-OCH3Or 4-OCH3(ii) a Or n is 2, two R are same and are respectively halogen, nitro, linear or branched alkyl or linear or branched alkoxy, or two R are adjacent and are connected together to form-O- (CH)2)p-O-。
As a preferred embodiment of the preparation method of the invention, n is 2, and two R are the same and are respectively 3-OCH3And 4-OCH3Or two R are adjacent and linked together to form 3,4 (O-CH)2-O)。
As a preferred embodiment of the preparation method of the present invention, the condensing agent is 1-ethyl-3 (3-dimethylpropylamine) carbodiimide (i.e., EDCI) and the catalyst is 4-dimethylaminopyridine (i.e., DMAP). When EDCI is used as a condensing agent and DMAP is used as a catalyst, the obtained target product has high yield and is easier to purify.
As a preferred embodiment of the preparation method of the present invention, the reaction temperature of the Steglich esterification reaction is 0 to 45 ℃ and the reaction time is 4 to 24 hours, and the molar ratio of the chrysin, the compound represented by the structural formula (2), the condensing agent and the catalyst is chrysin: a compound represented by structural formula (2): condensing agent: catalyst 1:1.5:1.5: 0.5.
In a preferred embodiment of the preparation method of the present invention, the reaction temperature of the Steglich esterification reaction is normal temperature, the reaction time is 6 hours, and the molar ratio of the chrysin, the compound represented by the structural formula (2), the condensing agent and the catalyst is chrysin: a compound represented by structural formula (2): condensing agent: catalyst 1:1.5:1.5: 0.5.
As a preferred embodiment of the preparation method of the invention, the Steglich esterification reaction is carried out under the protection of protective gas.
As a preferred embodiment of the preparation method of the present invention, the preparation method further comprises the steps of: and (3) carrying out solid-liquid separation on the system after the Steglich esterification reaction, collecting the solid, and washing the solid by using petroleum ether, ethyl acetate and acetone in sequence. After being washed by petroleum ether, ethyl acetate and acetone in sequence, impurities can be removed, and a pure target product is obtained.
As a preferred embodiment of the preparation method of the present invention, the preparation method further comprises the steps of: after the washing, a drying treatment is performed.
In a second aspect, the present invention provides chrysin cinnamate or a derivative thereof prepared by the above preparation method.
Compared with the prior art, the invention has the following advantages: the chrysin cinnamate or the derivative thereof is prepared from chrysin and cinnamic acid or the derivative thereof through a one-step method, the method is simple, the industrial production is easy, the yield of the target product is high and is more than 40%, and the obtained chrysin cinnamate or the derivative thereof has the characteristics of chrysin and cinnamic acid or the derivative thereof, so that a compound source is provided for biological activity screening.
Drawings
FIG. 1 is a reaction scheme for each example (starting material 2a corresponds to product 3a, starting material 2b corresponds to product 3c … …, and so on, starting material 2n corresponds to product 3 n);
figure 2 is the reaction mechanism of chrysin and cinnamic acid of the present invention.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.
The reagents used in the following examples were all analytical grade, and the apparatus used was an OptiMelt MPA100 melting point apparatus (SRS); bruker 500MHz NMR spectrometer (BRUKER, Germany, DMSO-d6 as solvent, TMS as internal standard); thermo Fisher LCQ fly model liquid chromatography-mass spectrometer (Thermo Fisher Seientific, USA).
Example 1
A50 mL round-bottom flask was charged with chrysin (compound of formula (1)) (1mmol,1eq), cinnamic acid (compound of formula (2 a)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in that order, and then placed under N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3a (chrysin cinnamate).
Example 2
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 b)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (3), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 b.
Example 3
In a 50mL round-bottom flask were added chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 c)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 c.
Example 4
In a 50mL round-bottom flask were added chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 d)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 d.
Example 5
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 e)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 e.
Example 6
To a 50mL round-bottomed flask were added chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 f)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0) in this order.5mmol,0.5eq) and then in N2Under the protection of (3), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 f.
Example 7
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 g)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain 3g of a compound.
The compound obtained 3 g: light yellow solid, yield 88.7%, m.p.234.6-237.2 ℃;1H NMR(500MHz,DMSO-d6):12.90(s,1H),8.15(d,J＝7.2Hz,2H),7.97–7.87(m,3H),7.64(dq,J＝14.6,7.1Hz,3H),7.56(d,J＝8.6Hz,2H),7.23(d,J＝2.1Hz,1H),7.20(s,1H),6.98(d,J＝16.0Hz,1H),6.79(d,J＝2.1Hz,1H)；LC-MS(ESI)m/z:C24H16ClO5{[M+H]+calculated value 419.06, actual value 419.07.
Example 8
Adding chrysin (compound shown in formula (1)) (1mmol,1eq) and cinnamic acid (structure) into a 50mL round-bottom flask in sequenceCompound of formula (2h) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq.) and DMAP (0.5mmol,0.5 eq.) followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain the compound for 3 h.
Example 9
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 i)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 i.
The compound 3i obtained: a light yellow solid, with a yield of 43.4%, m.p.184.7-186.3 ℃;1H NMR(500MHz,DMSO-d6):12.89(s,1H),8.15(d,J＝7.2Hz,2H),7.93(d,J＝16.0Hz,1H),7.79(dt,J＝10.1,2.1Hz,1H),7.72～7.58(m,4H),7.56～7.48(m,1H),7.33(td,J＝8.6,2.3Hz,1H),7.24(d,J＝2.0Hz,1H),7.20(s,1H),7.03(d,J＝16.1Hz,1H),6.80(d,J＝2.1Hz,1H)；13C NMR(125MHz,DMSO-d6):183.15,164.73,164.45,161.31,156.86,156.32,146.39,136.76,132.94,131.55,131.48,130.88,129.71,127.16,125.85,118.77,115.46,115.28,108.86,106.29,105.94,102.26；LC-MS(ESI)m/z:C24H15FNaO5{[M+Na]+calculated value 425.07, actual value 425.08.
Example 10
Adding chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 j)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in sequence into a 50mL round-bottomed flask, and adding the mixture into a flask2Under the protection of (3), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 j.
The compound 3j obtained: yellow solid, yield 72.5%, m.p.247.7-251.1 ℃;1H NMR(500MHz,DMSO-d6):12.90(s,1H),8.30(d,J＝8.8Hz,2H),8.19～8.09(m,4H),8.05(d,J＝16.0Hz,1H),7.69～7.58(m,3H),7.25(d,J＝2.1Hz,1H),7.19(d,J＝7.8Hz,1H),7.15(s,1H),6.82(d,J＝2.0Hz,1H)；13C NMR(125MHz,DMSO-d6):183.19,164.75,164.14,161.33,156.86,156.22,148.91,145.02,140.55,132.96,130.87,130.37,129.72,127.16,124.53,121.50,108.92,106.31,105.91,102.24；LC-MS(ESI)m/z:C24H15NKO7{[M+K]+calculated value 468.05, actual value 468.20.
Example 11
A50 mL round-bottom flask was charged with chrysin (compound of formula (1)) (1mmol,1eq), cinnamic acid (compound of formula (2 k)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in that order, and then placed under N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 k.
Compound 3k obtained: light yellow solid, yield 89.9%, m.p.169.2-172.5 ℃;1H NMR(500MHz,DMSO-d6):12.88(s,1H),8.15(d,J＝7.1Hz,2H),8.10(d,J＝16.1Hz,1H),7.84(dd,J＝7.8,1.7Hz,1H),7.69～7.58(m,3H),7.49(td,J＝8.1,7.6,1.6Hz,1H),7.22(d,J＝2.1Hz,1H),7.19(s,1H),7.16(d,J＝8.2Hz,1H),7.05(t,J＝7.5Hz,1H),6.91(d,J＝16.1Hz,1H),6.78(d,J＝2.1Hz,1H),3.91(s,3H)；13C NMR(125MHz,DMSO-d6):183.15,164.96,164.70,161.28,158.74,156.85,156.48,142.57,132.94,129.82,129.71,127.16,122.33,121.33,117.06,112.41,106.26,105.99,102.29,56.25；LC-MS(ESI)m/z:C25H18KO6{[M+K]+calculated value 453.07, actual value 453.19.
Example 12
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 l)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain 3l of a compound.
The compound 3l obtained: yellow solid, yield 73.4%, m.p.218.5-221.1 ℃;1H NMR(500MHz,DMSO-d6):12.88(s,1H),8.17～8.13(m,2H),7.88(d,J＝15.9Hz,1H),7.81(d,J＝8.8Hz,2H),7.67～7.59(m,3H),7.21(d,J＝2.0Hz,1H),7.19(s,1H),7.03(d,J＝8.7Hz,2H),6.81～6.75(m,2H),3.82(s,3H),3.83(s,3H)；13C NMR(125MHz,DMSO-d6):183.09,164.89,164.69,161.26,157.84,156.84,156.53,147.76,132.94,131.27,130.89,129.71,127.15,115.00,114.14,108.73,106.25,105.96,102.27,55.90；LC-MS(ESI)m/z:C25H19O6{[M+H]+calculated value 415.17, actual value 415.10.
Example 13
A50 mL round-bottomed flask was charged with chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 m)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in this order, followed by N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 m.
The resulting compound3 m: yellow solid, yield 74.4%, m.p.172.3-174.5 ℃;1H NMR(500MHz,DMSO-d6):12.88(s,1H),8.14(d,J＝7.2Hz,2H),7.85(d,J＝15.9Hz,1H),7.70～7.57(m,3H),7.48(d,J＝2.1Hz,1H),7.37(dd,J＝8.4,2.0Hz,1H),7.21(d,J＝2.1Hz,1H),7.19(s,1H),7.03(d,J＝8.4Hz,1H),6.85(d,J＝16.0Hz,1H),6.76(d,J＝2.0Hz,1H),3.83(d,J＝6.6Hz,6H)；13C NMR(125MHz,DMSO-d6):183.14,164.93,164.67,161.26,156.83,156.56,152.03,149.49,148.18,132.93,130.87,129.70,127.15,127.03,124.35,114.29,111.95,111.00,108.71,106.23,105.92,102.24,56.13,56.08；LC-MS(ESI)m/z:C26H20NaO7{[M+Na]+calculated value 467.11, actual value 467.10.
Example 14
A50 mL round-bottom flask was charged with chrysin (compound of formula (1)) (1mmol,1eq), cinnamic acid (compound of formula (2N)) (1.5mmol,1.5eq.), EDCI (1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) in that order, and then charged with N2Under the protection of (1), adding dichloromethane (10.0mL), reacting at normal temperature for about 6h (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3 n.
The compound 3n obtained: yellow solid, yield 90.6%, m.p.220.2-221.4 ℃;1H NMR(500MHz,DMSO-d6):12.88(s,1H),8.18～8.11(m,2H),7.84(d,J＝15.9Hz,1H),7.68～7.57(m,3H),7.55(d,J＝1.7Hz,1H),7.32(dd,J＝8.2,1.7Hz,1H),7.21(d,J＝2.1Hz,1H),7.18(s,1H),7.01(d,J＝8.0Hz,1H),6.79(d,J＝15.9Hz,1H),6.76(d,J＝2.0Hz,1H),6.12(s,2H)；13C NMR(125MHz,DMSO-d6):183.14,164.86,164.69,161.26,156.84,156.52,150.45,148.65,147.82,132.94,130.87,129.71,128.68,127.15,126.49,114.71,109.07,108.74,107.39,106.24,105.97,102.27；LC-MS(ESI)m/z:C25H17O7{[M+H]+calculated value 429.10, actual value 429.10.
Comparative example 1
Adding chrysin (compound shown in formula (1)) (1mmol,1eq) and cinnamic acid (shown in formula (2 a)) in a 50mL round-bottom flask in sequenceCompound) (1.5mmol,1.5eq.), then in N2Under the protection of (3), dichloromethane (10.0mL) was added and the reaction was carried out at room temperature for about 6 hours (TLC detection), and it was found that the reaction did not proceed and the target compound 3a could not be obtained.
Comparative example 2
In a 50mL round-bottom flask, chrysin (compound represented by formula (1)) (1mmol,1eq), cinnamic acid (compound represented by formula (2 a)) (1.5mmol,1.5eq.), DCC (N, N' -dicyclohexylcarbodiimide, 1.5mmol,1.5eq) and DMAP (0.5mmol,0.5eq) were added in this order, followed by addition of N2Under the protection of (3), adding dichloromethane (10.0mL), reacting at normal temperature for about 8h (TLC detection), after the reaction is finished, carrying out suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain a compound 3a, wherein the yield is 84.6%, but the obtained compound 3a still contains impurities.
Comparative example 3
Adding dichloromethane (10.0mL), cinnamic acid (compound shown in structural formula (2 a)) (1.5mmol,1.5eq.) and thionyl chloride (1.5mmol,1.5eq.) into a 50mL round-bottom flask in sequence, reacting at room temperature for about 8 hours, concentrating to remove the solvent, dissolving in dichloromethane (10.0mL) again, adding chrysin (compound shown in structural formula (1)) (1mmol,1 eq.) into the system, reacting at room temperature for about 8 hours (TLC detection), after the reaction is finished, performing suction filtration, washing a filter cake by using petroleum ether, ethyl acetate and acetone in sequence, and drying to obtain the compound 3a with the yield of 86.5%.
Comparing example 1 with comparative examples 1-3, it can be seen that the reaction does not proceed when no additional catalyst reagent is added; under the action of EDCI and DMAP, the reaction can be completed within 6h, the yield reaches 95.1%, and the obtained product is washed by petroleum ether, ethyl acetate and acetone in sequence to achieve purity; under the action of DCC and DMAP, the reaction time is longer, the yield is obviously reduced, and the purification difficulty of the obtained product is higher; using SOCl2Acylation of cinnamic acid followed by esterification with chrysin requires less reaction time, but requires two steps, with slightly lower yields and more stringent reaction conditions, so it is most appropriate to select conditions using EDCI and DMAP for carrying out the reaction.
The experimental results and literature reports baseOn the basis of[16-18]The inventors speculate that a possible reaction mechanism (see figure 2) is that first cinnamic acid reacts with EDCI to form a more reactive O-acylisourea, and then the hydroxyl group at C-7 of chrysin attacks the O-acylisourea to form the corresponding ester and EDCI by-products. At the same time, in order to prevent 1, 3-rearrangement of O-acylisourea in the reaction, the acyl transfer reagent DMAP was added to reduce the formation of by-products.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Reference to the literature
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Claims (10)
1. A preparation method of chrysin cinnamate or derivatives thereof is characterized by comprising the following steps: performing Steglich esterification reaction on chrysin and a compound shown in a structural formula (2) in an organic solvent under the action of a condensing agent and a catalyst to obtain chrysin cinnamate or a derivative thereof, wherein the structural formula of the chrysin cinnamate or the derivative thereof is shown in a formula (3);
each R is independently halogen, nitro, straight or branched chain alkyl, or straight or branched chain alkoxy, or two adjacent R are linked together to form-O (CH)2)pO-; n is an integer of 0 to 5; p is an integer of 1 or more.
2. The method according to claim 1, wherein n is 0, 1 or 2.
3. The method according to claim 2, wherein n is 1 and R is 2-CH3-、3-CH3-、4-CH3-、2-Cl、3-Cl、4-Cl、2-Br、3-Br、4-Br、2-F、3-F、4-F、2-NO2-、3-NO2-、4-NO2-、2-OCH3、3-OCH3Or 4-OCH3(ii) a Or n is 2, two R are same and are respectively halogen, nitro, linear or branched alkyl or linear or branched alkoxy, or two R are adjacent and are connected together to form-O- (CH)2)p-O-。
4. The method according to claim 3, wherein n is 2, and R's are the same and each is 3-OCH3And 4-OCH3Or two R are adjacent and linked together to form 3,4 (O-CH)2-O)。
5. The method according to claim 1, wherein the condensing agent is 1-ethyl-3 (3-dimethylpropylamine) carbodiimide and the catalyst is 4-dimethylaminopyridine.
6. The method as claimed in claim 1, wherein the reaction temperature of the Steglich esterification reaction is 0-45 ℃ and the reaction time is 4-24 hours, and the molar ratio of the chrysin, the compound represented by the structural formula (2), the condensing agent and the catalyst is chrysin: a compound represented by structural formula (2): condensing agent: catalyst 1:1.5:1.5: 0.5.
7. The method as claimed in claim 6, wherein the Steglich esterification reaction is carried out at normal temperature for 6 hours, and the molar ratio of chrysin, the compound represented by the structural formula (2), the condensing agent and the catalyst is chrysin: a compound represented by structural formula (2): condensing agent: catalyst 1:1.5:1.5: 0.5.
8. The process of claim 1, wherein the Steglich esterification reaction is carried out under protective gas.
9. The method of claim 1, further comprising the steps of: and (3) carrying out solid-liquid separation on the system after the Steglich esterification reaction, collecting the solid, washing the solid by using petroleum ether, ethyl acetate and acetone in sequence, and then drying.
10. Chrysin cinnamate or a derivative thereof obtainable by a process according to any one of claims 1 to 9.
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| CN114874124B (en) * | 2022-05-12 | 2023-07-04 | 五邑大学 | Melatonin cinnamic acid derivative and preparation method thereof |
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