CN112939916B - Method for synthesizing coumarin-3-carboxylic acid compounds by one-pot two-step method - Google Patents

Method for synthesizing coumarin-3-carboxylic acid compounds by one-pot two-step method Download PDF

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CN112939916B
CN112939916B CN202110286642.2A CN202110286642A CN112939916B CN 112939916 B CN112939916 B CN 112939916B CN 202110286642 A CN202110286642 A CN 202110286642A CN 112939916 B CN112939916 B CN 112939916B
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席高磊
陈芝飞
蔡莉莉
赵志伟
王清福
许克静
王秋领
于建春
付瑜锋
刘强
杜佳
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China Tobacco Henan Industrial Co Ltd
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Abstract

The invention relates to a method for synthesizing coumarin-3-carboxylic acid compounds by a one-pot two-step method, wherein the structural formula of the coumarin-3-carboxylic acid compounds is as follows:
Figure DDA0002980738570000011
wherein R is 1 Is H-, Cl-, Br, NO 2 ‑、CH 3 -, HO-; the synthetic process of the coumarin-3-carboxylic acid compounds comprises the following steps:
Figure DDA0002980738570000012
malonic acid, acetone and substituted salicylaldehyde are used as raw materials, iodine is used as a catalyst, acetic anhydride is used as a solvent, a series of coumarin-3-carboxylic acid compounds are synthesized by a one-pot series reaction, and the efficiency and the yield are greatly improved compared with a step method.

Description

Method for synthesizing coumarin-3-carboxylic acid compounds by one-pot two-step method
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing coumarin-3-carboxylic acid compounds by a one-pot method.
Background
Coumarin (also known as benzopyrone) widely exists in various natural products, has various pharmacological activities such as antibacterial, antioxidant, anticancer and anti-HIV virus, and is also an important intermediate for synthesizing medicines, pesticides, dyes and perfumes. Coumarin-3-carboxylic acid is an important derivative of coumarin, and the coumarin-3-carboxylic acid ethyl ester is synthesized by reacting salicylaldehyde with diethyl malonate in a Knoevenagel manner and then subjected to hydrolysis reaction step by step to obtain the coumarin-3-carboxylic acid, wherein the catalyst of the method comprises piperidine, diethylamine, sodium ethoxide, sodium methoxide and KF-Al 2 O 3 And the like. Diethyl malonate is usually obtained by esterification of malonic acid, and if coumarin-3-carboxylic acid is directly synthesized from malonic acid in one pot, the steps can be obviously simplified, and the cost is reduced.
The one-pot two-step series reaction is one of the leading edge and hot spots of the current organic synthesis research, and has wide application in the fields of total synthesis of natural products, combinatorial chemistry, heterocyclic compound synthesis and the like. The intermediates of the one-pot series reaction do not need to be separated, and the next reaction can be carried out, so that the operation steps are simplified, and the method can be used for designing unstable active intermediates; the series reaction is carried out in the same environment, so that the consumption, the variety and the by-product of a solvent and an eluant are reduced, the environment is protected, and the cost is reduced; the series reaction does not need intermediate separation, which is beneficial to improving the working efficiency and saving the time. Therefore, the method for directly synthesizing the coumarin-3-carboxylic acid compounds by the one-pot two-step method is a high-efficiency and low-cost method.
Disclosure of Invention
The invention aims to provide a method for synthesizing coumarin-3-carboxylic acid compounds by a one-pot two-step method, which is characterized in that malonic acid, acetone and substituted salicylaldehyde are used as raw materials, iodine is used as a catalyst, acetic anhydride is used as a solvent, a series of coumarin-3-carboxylic acid compounds are synthesized by a one-pot method through a series reaction, and the efficiency and the yield are greatly improved compared with a step method.
The invention is realized by the following technical scheme:
a method for synthesizing coumarin-3-carboxylic acid compounds by a one-pot two-step method, wherein the structural formula of the coumarin-3-carboxylic acid compounds is as follows:
Figure BDA0002980738550000021
wherein R is 1 Is H-, Cl-, Br, NO 2 -、CH 3 -、HO-，
The synthetic process of the coumarin-3-carboxylic acid compounds comprises the following steps:
Figure BDA0002980738550000022
preferably, the
Figure BDA0002980738550000023
At least comprise
Figure BDA0002980738550000024
Figure BDA0002980738550000025
Figure BDA0002980738550000031
Figure BDA0002980738550000032
One or more combinations thereof.
Preferably, the preparation method of the coumarin-3-carboxylic acid compounds comprises the following steps:
adding malonic acid, iodine, acetone and acetic anhydride into a reaction bottle, reacting in water bath at 30 ℃ for 4h, adding R group substituted salicylaldehyde and water, refluxing until the reaction is complete, cooling, and filtering to obtain a target product which is a white or colored solid.
Preferably, the molar ratio of the malonic acid, the iodine, the acetone and the acetic anhydride substituted salicylaldehyde to the water is 100: 2-7: 80-120: 100-.
Preferably, the molar ratio of malonic acid, iodine, acetone, acetic anhydride, substituted salicylaldehyde and water is 100: 4: 109: 127: 100: 5556.
the invention has the beneficial effects that:
according to the invention, coumarin-3-carboxylic acid is prepared by adopting a one-pot two-step reaction, firstly, malonic acid and acetone generate diethyl malonate under the catalytic action of acetic anhydride solution and iodine, R-group substituted salicylaldehyde is directly added without separation, and a Knoevenagel reaction is carried out to obtain a target product. The product after the first step reaction is directly involved in the second step reaction without separation, and the product of the first step is consumed while the second step reaction is carried out, so that the first step reaction is more thorough, and meanwhile, the acid in the first step reaction can be used as a catalyst for knoevenagel condensation of the Michelic acid and the substituted salicylaldehyde, so that the reaction yield can be further improved; the synthesis of the coumarin-3-carboxylic acid compounds adopts continuous operation without separation, and the efficiency and the yield are greatly improved compared with a step method.
Drawings
FIG. 1 is a NMR spectrum of coumarin-3-carboxylic acid (1);
FIG. 2 is a NMR carbon spectrum of coumarin-3-carboxylic acid (1);
FIG. 3 is a NMR spectrum of 5-chlorocoumarin-3-carboxylic acid (2);
FIG. 4 is a NMR C-spectrum of 5-chlorocoumarin-3-carboxylic acid (2);
FIG. 5 is a NMR spectrum of 6-chlorocoumarin-3-carboxylic acid (3);
FIG. 6 is a NMR carbon spectrum of 6-chlorocoumarin-3-carboxylic acid (3);
FIG. 7 is a NMR spectrum of 7-chlorocoumarin-3-carboxylic acid (4);
FIG. 8 is a NMR carbon spectrum of 7-chlorocoumarin-3-carboxylic acid (4);
FIG. 9 is a NMR spectrum of 8-chlorocoumarin-3-carboxylic acid (5);
FIG. 10 is a NMR carbon spectrum of 8-chlorocoumarin-3-carboxylic acid (5);
FIG. 11 is a NMR spectrum of 5-bromocoumarin-3-carboxylic acid (6);
FIG. 12 is a NMR carbon spectrum of 5-bromocoumarin-3-carboxylic acid (6);
FIG. 13 is a NMR spectrum of 6-bromocoumarin-3-carboxylic acid (7);
FIG. 14 is a NMR carbon spectrum of 6-bromocoumarin-3-carboxylic acid (7);
FIG. 15 is a NMR chart of 7-bromocoumarin-3-carboxylic acid (8);
FIG. 16 is a NMR carbon spectrum of 7-bromocoumarin-3-carboxylic acid (8);
FIG. 17 is a NMR spectrum of 8-bromocoumarin-3-carboxylic acid (9);
FIG. 18 is a NMR carbon spectrum of 8-bromocoumarin-3-carboxylic acid (9);
FIG. 19 is a NMR spectrum of 6-nitrocoumarin-3-carboxylic acid (10);
FIG. 20 is a NMR carbon spectrum of 6-nitrocoumarin-3-carboxylic acid (10);
FIG. 21 is a NMR chart of 7-methylcoumarin-3-carboxylic acid (11);
FIG. 22 is a NMR carbon spectrum of 7-methylcoumarin-3-carboxylic acid (11);
FIG. 23 is a NMR spectrum of 6-methoxycoumarin-3-carboxylic acid (12);
FIG. 24 is a NMR carbon spectrum of 6-methoxycoumarin-3-carboxylic acid (12);
FIG. 25 is a NMR chart of 7-methoxycoumarin-3-carboxylic acid (13);
FIG. 26 is a NMR carbon spectrum of 7-methoxycoumarin-3-carboxylic acid (13);
FIG. 27 is a NMR spectrum of 8-methoxycoumarin-3-carboxylic acid (14);
FIG. 28 is a NMR carbon spectrum of 8-methoxycoumarin-3-carboxylic acid (14);
FIG. 29 is a NMR chart of 5-hydroxycoumarin-3-carboxylic acid (15);
FIG. 30 is a NMR carbon spectrum of 5-hydroxycoumarin-3-carboxylic acid (15);
FIG. 31 is a NMR chart of 6-hydroxycoumarin-3-carboxylic acid (16);
FIG. 32 is a NMR carbon spectrum of 6-hydroxycoumarin-3-carboxylic acid (16);
FIG. 33 is a NMR spectrum of 7-hydroxycoumarin-3-carboxylic acid (17);
FIG. 34 is a NMR carbon spectrum of 7-hydroxycoumarin-3-carboxylic acid (17);
FIG. 35 is a NMR spectrum of 8-hydroxycoumarin-3-carboxylic acid (18);
FIG. 36 is a NMR carbon spectrum of 8-hydroxycoumarin-3-carboxylic acid (18).
Detailed Description
The technical solutions of the present invention are described in detail below by examples, and the following examples are only exemplary and can be used only for explaining and explaining the technical solutions of the present invention, but not construed as limiting the technical solutions of the present invention.
Example 1
Main experimental reagents and instruments: malonic acid, iodine, acetone, acetic anhydride, salicylaldehyde, water, salicylaldehyde, 2-chlorosalicylaldehyde, 3-chlorosalicylaldehyde, 4-chlorosalicylaldehyde, 5-chlorosalicylaldehyde, 2-bromosalicylaldehyde, 3-bromosalicylaldehyde, 4-bromosalicylaldehyde, 5-nitrosalicylaldehyde, 4-methylsalicylaldehyde, 3-methoxysalicylaldehyde, 4-methoxysalicylaldehyde, 5-methoxysalicylaldehyde, 2-hydroxysalicylaldehyde, 3-hydroxysalicylaldehyde, 4-hydroxysalicylaldehyde, 5-hydroxysalicylaldehyde, an electronic balance, a rotary evaporator, an electromagnetic heating jacket, and a Bruker Avance III 600MHz nuclear magnetic resonance spectrometer (Bruker corporation, USA).
Figure BDA0002980738550000061
The synthetic route of coumarin-3-carboxylic acid compounds is as follows: a25 mL round-bottom flask was charged with malonic acid (1.04g, 10mmol), iodine (0.1g), acetone (0.8g, 10.9mmol) and acetic anhydride (1.2mL) and reacted in a water bath at 30 ℃ for 3 h. Then substituted salicylaldehyde (10mmol) and water (10mL) are added and the reaction is refluxed for 2h to generate a white or colored solid. And after the reaction is finished, cooling to room temperature, performing suction filtration, washing the solid for multiple times, and drying to obtain the coumarin-3-carboxylic acid (1-18) with the yield of more than 70%.
Coumarin-3-carboxylic acid target product structure:
Figure BDA0002980738550000062
the structures of the target compounds 1 to 18 were examined by Bruker Avance III 600MHz NMR spectrometer (Bruker, USA), and the nuclear hydrogen spectrum and carbon spectrum are shown in the figure.
Structural characterization data of coumarin-3-carboxylic acid compounds (1-18):
coumarin-3-carboxylic acid (1) white solid, yield 85.4%, melting point: 178-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.26(s,1H),8.75(s,1H),7.91(dd,J＝1.2Hz,J＝7.8Hz,1H),7.91(td,J＝1.8Hz,J＝8.4Hz,1H),7.44(d,J＝7.8Hz,1H),7.41(dd,J＝1.2Hz,J＝7.8Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.5,157.2,154.9,148.9,134.8,130.7,125.3,118.8,118.5,116.6。
5-chlorocoumarin-3-carboxylic acid (2) as a white solid in 72.3% yield, m.p.: 204-206 deg.c, 1 H NMR(600MHz,DMSO-d 6 )δ:13.52(s,1H),8.64(s,1H),7.72(t,J＝7.8Hz,1H),7.54(d,J＝7.2Hz,1H),7.43(d,J＝8.4Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.0,156.1,155.8,143.6,135.2,133.0,125.8,120.1,116.7,116.2。
6-chlorocoumarin-3-carboxylic acid (3) as a pale gray solid in 70.4% yield, m.p.: 189 a-191 a, 1 HNMR(600MHz,DMSO-d 6 )δ:13.42(s,1H),8.70(s,1H),8.03(d,J＝2.4Hz,1H),7.76(dd,J＝2.4Hz,J＝9.0Hz,1H),7.48(d,J＝9.0Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.2,156.6,153.6,147.6,134.1,129.5,128.9,120.0,119.8,118.7。
7-chlorocoumarin-3-carboxylic acid (4) as a white solid in a yield of 74.6%, a melting point of 117-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.35(s,1H),8.76(s,1H),7.93(d,J＝8.4Hz,1H),7.64(d,J＝2.4Hz,1H),7.48(dd,J＝1.8Hz,J＝8.4Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.3,156.5,155.4,148.2,139.0,132.0,125.6,118.8,117.5,116.8。
8-chlorocoumarin-3-carboxylic acid (5) as a yellow solid in 67.0% yield, mp: 184-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.52(s,1H),8.64(s,1H),7.72(t,J＝7.8Hz,1H),7.54(d,J＝7.2Hz,1H),7.43(d,J＝8.4Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.0,156.1,155.8,143.6,135.2,133.0,125.8,120.1,116.7,116.2。
g of 5-bromocoumarin-3-carboxylic acid (6) as a yellow solid, yield 63.3%, melting point: 182 ℃ and 183 ℃ are added, 1 H NMR(600MHz,DMSO-d 6 )δ:13.55(s,1H),8.61(d,J＝0.6Hz,1H),7.71(dd,J＝0.6Hz,J＝8.4Hz,1H),7.65(t,J＝8.4Hz,1H),7.47(d,J＝8.4Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.0,156.2,155.8,146.2,135.5,129.2,123.5,120.2,118.1,116.8。
6-bromocoumarin-3-carboxylic acid (7) as a yellow solid in 65.5% yield, m.p.: at a temperature of 296-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.54(s,1H),8.69(s,1H),8.17(d,J＝2.4Hz,1H),7.87(dd,J＝2.4Hz,J＝9.0Hz,1H),7.76(d,J＝9.0Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.3,156.5,155.3,148.3,132.0,128.4,127.8,119.6,119.0,117.8。
7-bromocoumarin-3-carboxylic acid (8) as a yellow solid in a yield of 72.1%, a melting point of 200-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.33(s,1H),8.74(s,1H),7.84(d,J＝8.4Hz,1H),7.76(d,J＝1.8Hz,1H),7.61(dd,J＝1.8Hz,J＝8.4Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.3,156.5,155.3,148.3,132.0,128.4,127.8,119.6,119.0,117.8。
8-bromocoumarin-3-carboxylic acid (9) as a white solid in 68.4% yield, melting point: 167-, 1 H NMR(600MHz,DMSO-d 6 )δ:13.41(s,1H),8.77(s,1H),8.02(dd,J＝1.2Hz,J＝7.8Hz,1H),7.93(dd,J＝1.2Hz,J＝7.8Hz,1H),7.35(d,J＝7.8Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.2,156.2,151.5,148.7,137.5,130.3,126.3,120.1,119.5,109.1。
6-Nitropoumarin-3-carboxylic acid (10) as an yellowish solid in 52.8% yield, mp: 169-172 ℃ of high temperature, 1 H NMR(600MHz,DMSO-d 6 )δ:13.55(s,1H),8.91(d,J＝3.0Hz,1H),8.90(s,1H),8.50(dd,J＝3.0Hz,J＝9.0Hz,1H),7.65(d,J＝9.0Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.0,158.5,155.9,147.7,144.1,128.8,126.4,120.8,118.8,118.2。
7-methylcoumarin-3-carboxylic acid (11) as a white solid in 82.4% yield, mp: 193-196 ℃ of the total weight of the mixture, 1 H NMR(600MHz,DMSO-d 6 )δ:13.15(s,1H),8.72(s,1H),7.79(d,J＝7.8Hz,1H),7.27(s,1H),7.24(d,J＝7.8Hz,1H),2.44(s,3H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.5,157.4,155.1,149.0,146.3,130.4,126.5,117.4,116.6,116.1,22.0。
6-Methoxycoumarin-3-carboxylic acid (12) as a yellow solid, yield 87.1%, m.p.: 117 ℃ and 119 ℃ in sequence, 1 H NMR(600MHz,DMSO-d 6 )δ:13.26(s,1H),8.69(s,1H),7.47(d,J＝3.0Hz,1H),7.39(d,J＝9.0Hz,1H),7.32(dd,J＝3.0Hz,J＝9.0Hz,1H),3.81(s,3H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.5,157.4,156.2,149.4,148.7,122.5,119.0,118.9,117.7,112.3,56.3。
7-Methoxycoumarin-3-carboxylic acid (13) as a pale yellow solid, yield 89.5%, melting point: 191-193 ℃ of the temperature of the reaction kettle, 1 H NMR(600MHz,DMSO-d 6 )δ:12.99(s,1H),8.72(s,1H),7.83(d,J＝9.0Hz,1H),7.04(d,J＝3.0Hz,1H),7.01(dd,J＝2.4Hz,J＝8.4Hz,1H),3.89(s,3H)； 13 C NMR(150MHz,DMSO-d 6 )δ:165.1,164.6,157.7,157.4,149.6,132.0,114.3,113.8,112.1,100.7,56.7。
8-Methoxycoumarin-3-carboxylic acid (14) g as yellow solid, 91.2% yield, m.p.: 166-168 ℃ of the reaction kettle, 1 H NMR(600MHz,DMSO-d 6 )δ:13.29(s,1H),8.72(s,1H),7.44(dd,J＝1.2Hz,J＝7.8Hz,1H),7.41(dd,J＝1.2Hz,J＝7.8Hz,1H),7.33(d,J＝7.8Hz,1H),3.92(s,3H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.5,156.9,149.1,146.7,144.3,125.2,121.6,119.0,118.9,116.7,56.6。
5-Hydroxycoumarin-3-carboxylic acid (15) as a yellow solidYield 81.4%, melting point: 283 the temperature of 284 ℃ to obtain the final product, 1 HNMR(600MHz,DMSO-d 6 )δ:13.09(s,1H),11.23(s,1H),8.75(s,1H),7.53(t,J＝7.8Hz,1H),6.83(d,J＝8.4Hz,1H),6.79(d,J＝7.8Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.4,157.3,156.9,156.1,144.2,136.1,115.5,110.7,108.2,106.8。
6-Hydroxycoumarin-3-carboxylic acid (16) as a yellow solid in 83.7% yield, mp: 281-282 ℃ of the temperature of the reaction kettle, 1 HNMR(600MHz,DMSO-d 6 )δ:13.21(s,1H),9.91(s,1H),8.67(s,1H),7.29(d,J＝9.0Hz,1H),7.21(d,J＝2.4Hz,1H),7.16(dd,J＝2.4Hz,J＝9.0Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.6,157.7,154.4,148.8,148.3,122.9,119.0,118.8,117.6,114.2。
7-Hydroxycoumarin-3-carboxylic acid (17) in light earthy yellow solid in 86.6% yield, m.p.: 253 at a temperature of 260 ℃ and a temperature of 260 ℃, 1 H NMR(600MHz,DMSO-d 6 )δ:12.81(s,1H),11.10(s,1H),8.69(s,1H),7.53(d,J＝7.8Hz,1H),6.85(dd,J＝2.4Hz,J＝8.4Hz,1H),6.79(d,J＝1.8Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.7,164.4,158.0,157.5,149.9,132.5,114.5,113.0,111.1,102.3.
8-Hydroxycoumarin-3-carboxylic acid (18) as a yellow solid in 75.0% yield, mp: 288-290 deg.c of water, 1 HNMR(600MHz,DMSO-d 6 )δ:13.24(s,1H),10.38(s,1H),8.69(s,1H),7.32(t,J＝4.8Hz,1H),7.21(d,J＝4.8Hz,1H),6.79(d,J＝7.8Hz,1H)； 13 C NMR(150MHz,DMSO-d 6 )δ:164.6,157.2,149.4,144.9,143.6,125.3,120.8,120.5,119.4,118.6
comparative example 1
The coumarin-3-carboxylic acid compounds are synthesized by steps:
1. synthesis of Meldrum's acid:
Figure BDA0002980738550000111
in a 100mL round-bottom flask, malonic acid (10.4g, 100mmol), iodine (0.2g), acetone (8g, 109mmol) and acetic anhydride (12mL) were added and reacted in a 30 ℃ water bath for 4 h. After the reaction is finished, the reaction product is cooled to 0 ℃, solid is separated out, the reaction product is filtered, washed by ice water and glacial ethanol in sequence and dried to obtain 12.38g of white needle-shaped solid Meldrum's acid, the yield is 86 percent, and the temperature is between m.p.94 and 96 ℃.
2. Synthesis of coumarin-3-carboxylic acid compounds:
Figure BDA0002980738550000112
a100 mL round-bottom flask was charged with substituted salicylaldehyde (20mmol), Meldrum's acid (3.2g, 22mmol), and water (20mL), and the reaction was refluxed for 4 hours to precipitate a solid. After the reaction is finished, cooling to room temperature, carrying out suction filtration, washing the solid for multiple times, and then drying to obtain the coumarin-3-carboxylic acid compounds 1-18 with the yield of 54.3% -95.6.
The invention synthesizes a series of coumarin-3-carboxylic acid compounds through a one-pot method series reaction, and the yield and the step-by-step reaction yield (namely comparative example 1) are compared in a table 1.
TABLE 1 comparison of the reaction yields of the stepwise reaction and the one-pot reaction
Figure BDA0002980738550000113
Figure BDA0002980738550000121
As can be seen from Table 1: in the process of synthesizing the coumarin-3-carboxylic acid compounds, the one-pot yield of 18 target compounds is higher than the total yield of step-by-step reactions, and the yield is improved by 5.8% -11.8%, so that the yield of the synthesized coumarin-3-carboxylic acid compounds is effectively improved by adopting the one-pot two-step series reaction, and the method has important application value. The reason for analysis is that in the reaction process of the one-pot method, knoevenagel is condensed to generate coumarin-3-carboxylic acid compounds, and meanwhile, the generation reaction of the Meldrum's acid is promoted, and then the Meldrum's acid and the substituted salicylaldehyde are promoted to be continuously condensed to generate the coumarin-3-carboxylic acid compounds; meanwhile, the acid in the first step of reaction can be used as a catalyst for knoevenagel condensation of the Meldrum's acid and the substituted salicylaldehyde, and the reaction yield can be further improved.
Experiments show that the one-pot reaction yield is obviously higher than that of the step-by-step reaction, and meanwhile, the intermediate of the one-pot series reaction does not need to be separated and can be subjected to the next step of reaction, so that the operation steps are simplified, the purification of the intermediate product is omitted, the work efficiency is improved, the time is saved, the dosage of the solvent is reduced, the environment is protected, and the cost is reduced.
The above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.

Claims (5)

1. The method for synthesizing the coumarin-3-carboxylic acid compounds by the one-pot two-step method is characterized in that the structural formula of the coumarin-3-carboxylic acid compounds is as follows:
Figure FDA0003681765970000011
wherein R is 1 Is H-, Cl-, Br, NO 2 -、CH 3 -、HO-；
The synthetic process of the coumarin-3-carboxylic acid compounds comprises the following steps:
Figure FDA0003681765970000012
2. the method for synthesizing coumarin-3-carboxylic acids by the one-pot two-step method according to claim 1, wherein the method comprises
Figure FDA0003681765970000013
Is selected from
Figure FDA0003681765970000014
Figure FDA0003681765970000015
3. The method for synthesizing coumarin-3-carboxylic acids by the one-pot two-step method according to claim 1, wherein the method for preparing the coumarin-3-carboxylic acids comprises the following steps:
adding malonic acid, iodine, acetone and acetic anhydride into a reaction bottle, reacting in water bath at 30 ℃ for 4h, and adding R 1 The salicylic aldehyde and water are substituted by the group, the reflux is carried out until the reaction is completed, and the target product of white or colored solid is obtained after cooling and filtering.
4. The method of claim 3, wherein the molar ratio of malonic acid, iodine, acetone, acetic anhydride, substituted salicylaldehyde and water is 100: 2-7: 80-120: 100: 140: 100: 3000-7000.
5. The method of claim 4, wherein the molar ratio of malonic acid, iodine, acetone, acetic anhydride, substituted salicylaldehyde and water is 100: 4: 109: 127: 100: 5556.
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