Method for synthesizing 4-formyl-7-methylcoumarin by microwave-assisted method

Abstract

The invention discloses a method for synthesizing 4-formyl-7-methyl coumarin by a microwave-assisted method, relates to a method for synthesizing 4-formyl-7-methyl coumarin, and aims to solve the problems of long reaction time and low yield of the existing method for synthesizing 4-formyl-7-methyl coumarin. The method comprises the following steps: respectively adding 4, 7-dimethyl coumarin, a solvent and a catalyst into a reactor, reacting under the assistance of microwaves, and tracking and detecting until the 4, 7-dimethyl coumarin disappears; adding water into the reaction liquid for quenching, filtering, extracting, concentrating and refining to obtain 4-formyl-7-methylcoumarin; the yield reaches 88%-98%. The method has the advantages of easily available raw materials, low cost, mild reaction conditions, easiness in control, simplicity and convenience in operation and strong industrialization, and can be applied to the field of organic synthesis.

Description

Technical Field

[0001] The invention relates to a synthesis method of 4-aldehyde-7-methylcoumarin and relates to the technical field of organic synthesis. Background Art

[0002] Coumarin and its derivatives are widely found in plants and are an important class of natural compounds. Related research results show that coumarin and its derivatives have biological activities such as anti-inflammatory, antibacterial, anticancer and anticoagulant. An article on pages 1744-1756 of Volume 143 of the European Journal of Medicinal Chemistry in 2017 disclosed a method for synthesizing compounds with anti-inflammatory and antibacterial activities using 4-formyl-7-methyl coumarin as a raw material. Regarding the synthesis report of 4-formyl-7-methyl coumarin, an article on pages 1002-1008 of the 8th issue of Synthetic Communication in 2015 disclosed a method for synthesizing 4-formyl-7-methyl coumarin using 4-bromomethyl coumarin as a raw material. However, the synthesis of 4-formyl-7-methyl coumarin reported above has the limitations of long reaction time and low yield. It is urgent to explore an efficient and green method for preparing 4-formyl coumarin derivatives. Summary of the invention

[0003] The invention aims to solve the problems of long reaction time and low yield of the existing C-4 aldehyde coumarin derivative synthesis, and provides a method for synthesizing 4-aldehyde-7-methyl coumarin by microwave-assisted method.

[0004] The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of the present invention is carried out according to the following steps:

[0005] 1. Add 4,7-dimethylcoumarin, 1,4-dioxane and catalyst into the reactor and mix them evenly;

[0006] 2. Using microwave-assisted reaction, the temperature is raised to 60-100°C under the condition of microwave power of 50-150W, and the reaction of 4,7-dimethylcoumarin is monitored. When the reaction of 4,7-dimethylcoumarin is complete, water is added to quench the reaction, and the reaction is cooled to room temperature, filtered, the filtrate is extracted, the solvent is recovered by evaporation, refined, and dried to obtain 4-aldehyde-7-methylcoumarin.

[0007] Furthermore, the mass of 1,4-dioxane added in step 1 is 4-8 times the mass of 4,7-dimethylcoumarin;

[0008] Furthermore, the catalyst in step 1 is manganese dioxide and a sulfuric acid solution with a mass percentage concentration of 60% to 70%, or the catalyst is selenium dioxide.

[0009] Furthermore, the mass of the manganese dioxide added as the catalyst in step 1 is 1% to 3% of the mass of 4,7-dimethylcoumarin, and the mass of the sulfuric acid solution with a mass percentage concentration of 60% to 70% is 0.5 to 1 times the mass of the manganese dioxide;

[0010] Furthermore, the sulfuric acid solution with a mass percentage concentration of 60% to 70% is added in a dropwise manner, and the dropwise addition time is 10 to 30 minutes.

[0011] Furthermore, the mass of the added catalyst selenium dioxide in step 1 is 0.4 to 1 times the mass of 4,7-dimethylcoumarin.

[0012] Furthermore, the monitoring of the reaction of 4,7-dimethylcoumarin in step 2 is performed by thin layer chromatography (TLC), wherein the developing solvent is a mixture of n-hexane and ethyl acetate in a volume ratio of 4:1.

[0013] Furthermore, in the step 2, when water is added to quench the reaction, the mass of the added water is 1 to 2 times the mass of 1,4-dioxane.

[0014] Furthermore, the extraction in step 2 is performed using ethyl acetate, and the mass of the ethyl acetate is equal to the mass of the added water.

[0015] Furthermore, the purification described in step 2 is performed by recrystallization using anhydrous ethanol.

[0016] The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of the present invention has the following synthesis path:

[0017]

[0018] The present invention utilizes a microwave-assisted method to synthesize 4-aldehyde-7-methylcoumarin, wherein 4,7-dimethylcoumarin, a solvent and a catalyst are added into a reactor, uniformly mixed at room temperature, microwave reaction is performed, after the reaction is detected, water is added for quenching, filtration, extraction, rotary evaporation for solvent recovery, refining, drying, and 4-aldehyde-7-methylcoumarin is obtained, and the yield reaches 88% to 98%. The method of the present invention has the advantages of easy availability of raw materials, low cost, mild reaction conditions, short reaction time, easy control, simple operation, strong industrialization, and good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The 4-aldehyde-7-methylcoumarin prepared in Example 1 1 H-NMR spectrum;

[0020] Figure 2 The 4-aldehyde-7-methylcoumarin prepared in Example 1 13 C-NMR spectrum. DETAILED DESCRIPTION

[0021] The beneficial effects of the present invention are verified by the following examples.

[0022] Example 1: The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of this example is carried out according to the following steps:

[0023] 1. In a reactor, add 87 g (0.5 mol) of 4,7-dimethylcoumarin, 348 g of 1,4-dioxane, and 0.87 g of manganese dioxide, mix them evenly at room temperature, and drop 0.50 g of a 65% sulfuric acid solution. The sulfuric acid solution is added dropwise within 10 minutes to obtain a reaction solution;

[0024] 2. The reaction solution obtained in step 1 was heated to 60°C under a microwave power of 50 W, and the reaction of 4,7-dimethylcoumarin was monitored by TLC. After reacting for 2 hours, TLC monitoring showed that the reaction was complete; 500 g of water was added to quench the reaction, and the filtrate was filtered with suction. 500 g of ethyl acetate was added to the filtrate for extraction three times, the extracts were combined, and the solvent was recovered by concentration under reduced pressure. The crude product was recrystallized with anhydrous ethanol and dried to obtain 4-aldehyde-7-methylcoumarin.

[0025] In this example, the mass of 4-aldehyde-7-methylcoumarin is 88.2 g, and the yield is 90%.

[0026] The 4-aldehyde-7-methylcoumarin obtained in this embodiment was subjected to 1 H-NMR (600MHz, CDCl3) spectrum test, the results are: 1 H-NMR (600MHz,CDCl3)δ10.11(s,1H,-CHO),8.45(d,1H,J=8.4Hz,H-5),7.20(s,1H),7.17(d,1H,J=1.2Hz,H-8),7.19(dd,1H,J=8.4,1.2Hz,H-6),6.82(s,1H,H-3),2.47(s,3H,-CH3). The spectrum is shown in Figure 1 shown.

[0027] The 4-aldehyde-7-methylcoumarin obtained in this embodiment was subjected to 13 C-NMR (150MHz, CDCl3) spectrum test results are 13C-NMR (150MHz, CDCl3)δ191.5,160.6,154.6,144.3,143.8,126.5,125.9,124.4,117.3,112.3,21.8. The spectrum is as follows Figure 2 shown.

[0028] from Figure 1 and Figure 2 It can be seen from the test results that the structural formula of the product obtained in this embodiment is:

[0029] That is 4-formyl-7-methylcoumarin.

[0030] Example 2: The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of this example is carried out according to the following steps:

[0031] 1. In a reactor, add 87 g (0.5 mol) of 4,7-dimethylcoumarin, 348 g of 1,4-dioxane, and 1.74 g of manganese dioxide, mix well at room temperature, and then dropwise add 0.80 g of a 65% sulfuric acid solution over 30 minutes to obtain a reaction solution;

[0032] 2. The reaction solution obtained in step 1 was heated to 80°C by microwave, with a microwave power of 100 W, and the reaction progress was monitored by TLC. After 1 hour of reaction, the reaction was completed by TLC monitoring; 500 g of water was added to quench the reaction, and the filtrate was filtered with suction. 500 g of ethyl acetate was added to the filtrate for extraction three times, the extracts were combined, and the ethyl acetate was recovered by concentration under reduced pressure. The crude product was recrystallized with anhydrous ethanol and dried to obtain 4-aldehyde-7-methylcoumarin.

[0033] The yield of 4-aldehyde-7-methylcoumarin obtained in this example is 92.1 g, and the yield is 98%.

[0034] Example 3 The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of this embodiment is carried out according to the following steps:

[0035] 1. In a reactor, add 87 g (0.5 mol) of 4,7-dimethylcoumarin, 348 g of 1,4-dioxane, and 34.8 g of selenium dioxide, and mix them evenly at room temperature to obtain a reaction solution;

[0036] 2. The reaction solution obtained in step 1 was heated to 90°C by microwave, with a microwave power of 120 W, and the reaction progress was monitored by TLC. After 4 hours of reaction, the reaction was complete by TLC monitoring; 500 g of water was added to quench the reaction, and the mixture was filtered with suction. 500 g of ethyl acetate was added to the filtrate and extracted three times. The extracts were combined, concentrated under reduced pressure to recover the solvent, and the crude product was recrystallized with anhydrous ethanol and dried to obtain 4-aldehyde-7-methylcoumarin.

[0037] The mass of 4-aldehyde-7-methylcoumarin obtained in this example is 89.3 g, and the yield is 88%.

[0038] Example 4: The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method of this example is carried out according to the following steps:

[0039] 1. In a reactor, add 87 g (0.5 mol) of 4,7-dimethylcoumarin, 348 g of 1,4-dioxane, and 69.6 g of selenium dioxide, and mix them evenly at room temperature to obtain a reaction solution;

[0040] 2. The reaction solution obtained in step 1 was heated to 100°C by microwave, and the microwave power was 150W. The reaction progress was monitored by TLC. After 2 hours of reaction, the reaction was complete by TLC monitoring. 500g of water was added to quench the reaction, and the mixture was filtered. 500g of ethyl acetate was added to the filtrate and extracted three times. The extracts were combined, concentrated under reduced pressure to remove ethyl acetate, recrystallized with anhydrous ethanol, and dried to obtain 4-aldehyde-7-methylcoumarin.

[0041] The mass of 4-aldehyde-7-methylcoumarin obtained in this example is 90.2 g, and the yield is 96%.

[0042] The above-described embodiments describe the main features and basic principles of the present invention. Various improvements and changes may be made based on the principles and features of the present invention. Any improvements and changes made are within the protection scope of the present invention.

Claims

1. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method, characterized in that: The method proceeds as follows:

1. Add 4,7-dimethylcoumarin, 1,4-dioxane and catalyst into the reactor and mix them evenly; 2. Using microwave-assisted reaction, the temperature is raised to 60-100°C under the condition of microwave power of 50-150W, and the reaction of 4,7-dimethylcoumarin is monitored. When the reaction of 4,7-dimethylcoumarin is complete, water is added to quench the reaction, and the reaction is cooled to room temperature, filtered, the filtrate is extracted, the solvent is recovered by evaporation, refined, and dried to obtain 4-aldehyde-7-methylcoumarin.

2. The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1, characterized in that: The mass of 1,4-dioxane added in step 1 is 4-8 times the mass of 4,7-dimethylcoumarin.

3. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1 or 2, characterized in that: The catalyst described in step 1 is manganese dioxide and a sulfuric acid solution with a mass percentage concentration of 60% to 70%, or the catalyst is selenium dioxide.

4. The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 3, characterized in that: The mass of the manganese dioxide added as the catalyst in step 1 is 1% to 3% of the mass of 4,7-dimethylcoumarin, and the mass of the sulfuric acid solution added with a mass percentage concentration of 60% to 70% is 0.5 to 1 times the mass of the manganese dioxide.

5. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 3 or 4, characterized in that: The sulfuric acid solution with a mass percentage concentration of 60% to 70% is added in a dropwise manner, and the dropwise addition time is 10 to 30 minutes.

6. The method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 3, characterized in that: The added mass of the catalyst selenium dioxide described in step 1 is 0.4 to 1 times the mass of 4,7-dimethylcoumarin.

7. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1 or 2, characterized in that: The monitoring of the reaction of 4,7-dimethylcoumarin in step 2 is performed by thin layer chromatography, wherein the developing solvent is a mixture of n-hexane and ethyl acetate in a volume ratio of 4:

1.

8. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1 or 2, characterized in that: In step 2, water is added to quench the reaction, and the mass of the added water is 1 to 2 times the mass of 1,4-dioxane.

9. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1 or 2, characterized in that: The extraction described in step 2 is performed using ethyl acetate, and the mass of the ethyl acetate is equal to the mass of the added water.

10. A method for synthesizing 4-aldehyde-7-methylcoumarin by microwave-assisted method according to claim 1 or 2, characterized in that: The purification described in step 2 is to recrystallize using anhydrous ethanol.

Images