Synthesis method of 4-hydroxycoumarin

Abstract

The invention discloses a synthesis method of 4-hydroxycoumarin, and particularly relates to the technical field of synthesis of 4-hydroxycoumarin, and the synthesis method comprises the following steps: step 1, adding 1000 ml of toluene into a 2000 ml four-mouth bottle, then adding anion resin, and stirring for dissolving; 2, raising the temperature to 70 DEG C, starting to dropwise add a mixture of o-hydroxyacetophenone and diethyl carbonate, and slowly dropwise adding at a controlled dropwise adding speed; 3, after dropwise adding is completed, the temperature is kept at 90 DEG C, and a reaction is conducted. According to the method, the o-hydroxyacetophenone and the diethyl carbonate are used as raw materials, and the final product 4-hydroxycoumarin can be obtained through one-step reaction under the action of the anion exchange resin, so that the anion exchange resin can completely replace organic alkali to serve as a catalyst and can be repeatedly used for 10 times without influencing the yield, the cost is greatly reduced, the use of acid and alkali is reduced, and the method is suitable for industrial production. The process is safe, the yield reaches the standard, the product quality reaches the standard, the cost advantage is achieved, and the production conditions are met.

Description

Technical Field

[0001] The invention relates to the technical field of 4-hydroxycoumarin synthesis, and more specifically to a method for synthesizing 4-hydroxycoumarin. Background Art

[0002] The compound 4-hydroxycoumarin has important physiological activities such as antibacterial, anticoagulant and antitumor, and has high economic and medical value. At present, the synthesis of 4-hydroxycoumarin in industry mainly has the disadvantages of high alkali content, large solvent usage and large amount of wastewater.

[0003] Therefore, a method for synthesizing 4-hydroxycoumarin is needed. Summary of the invention

[0004] In order to overcome the above-mentioned defects of the prior art, the embodiments of the present invention provide a method for synthesizing 4-hydroxycoumarin, so that anion exchange resin can completely replace organic base as a catalyst, can be repeatedly used 10 times without affecting the yield, greatly reducing costs, reducing the use of acid and alkali, greatly reducing the three wastes, and having a safe process, a qualified yield, and a qualified product quality, with cost advantages and in line with production conditions, so as to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above object, the present invention provides the following technical solution: a method for synthesizing 4-hydroxycoumarin, comprising the following steps:

[0006] Step 1: Add 1000 ml of toluene into a 2000 ml four-necked bottle, then add anion resin and stir to dissolve;

[0007] Step 2: Raise the temperature to 70°C, start dropping a mixture of o-hydroxyacetophenone and diethyl carbonate, and slowly drop by dropping at a controlled speed;

[0008] Step 3: After the addition is complete, maintain the temperature at 90°C for reaction;

[0009] Step 4: After the reaction is completed, add 1000 ml of water to dissolve the reaction material and stir;

[0010] Step 5: Separate the layers, adjust the pH of the aqueous layer to 1-2 with HCL, and the product precipitates;

[0011] Step 6: Filter to obtain a crude product;

[0012] Step 7: Weigh 200 g of the crude product, dissolve it in 1000 ml of 70% ethanol, raise the temperature to 60°C, add activated carbon for decolorization for 30 minutes, and filter the activated carbon while it is hot;

[0013] Step 8: Cooling the ethanol solution to about 10°C, and centrifuging to obtain the product;

[0014] Step 9: Dry the product;

[0015] Step 10: HPLC content detection 99.3%, yield 91%.

[0016] In a preferred embodiment, the mass of the anion resin in step 1 is 10 grams.

[0017] In a preferred embodiment, the mass of o-hydroxyacetophenone in step 2 is 100 grams, and the mass of diethyl carbonate in step 2 is 200 grams.

[0018] In a preferred embodiment, the reaction time in step three is 3 hours.

[0019] In a preferred embodiment, the stirring time in step 4 is 30 minutes.

[0020] In a preferred embodiment, the temperature used for drying in step nine is 80°C.

[0021] In a preferred embodiment, the drying time in step nine is 4 hours.

[0022] Technical effects and advantages of the present invention:

[0023] The invention uses o-hydroxyacetophenone and diethyl carbonate as raw materials, and the final product 4-hydroxycoumarin can be obtained by the next step of reaction under the action of anion exchange resin, so that the anion exchange resin can completely replace the organic base as a catalyst, can be repeatedly used 10 times without affecting the yield, greatly reduces the cost, reduces the use of acid and alkali, greatly reduces the three wastes, has a safe process, meets the yield standard, meets the product quality standard, has a cost advantage, and meets the production conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The present invention is a synthetic process route diagram of 4-hydroxycoumarin. DETAILED DESCRIPTION

[0025] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] Example

[0027] As attached Figure 1 As shown, the present invention provides a method for synthesizing 4-hydroxycoumarin, comprising the following steps:

[0028] Step 1: Add 1000 ml of toluene into a 2000 ml four-necked bottle, then add anion resin and stir to dissolve;

[0029] Step 2: Raise the temperature to 70°C, start dropping a mixture of o-hydroxyacetophenone and diethyl carbonate, and slowly drop by dropping at a controlled speed;

[0030] Step 3: After the addition is complete, maintain the temperature at 90°C for reaction;

[0031] Step 4: After the reaction is completed, add 1000 ml of water to dissolve the reaction material and stir;

[0032] Step 5: Separate the layers, adjust the pH of the aqueous layer to 1-2 with HCL, and the product precipitates;

[0033] Step 6: Filter to obtain a crude product;

[0034] Step 7: Weigh 200 g of the crude product, dissolve it in 1000 ml of 70% ethanol, raise the temperature to 60°C, add activated carbon for decolorization for 30 minutes, and filter the activated carbon while it is hot;

[0035] Step 8: Cooling the ethanol solution to about 10°C, and centrifuging to obtain the product;

[0036] Step 9: Dry the product;

[0037] Step 10: HPLC content detection 99.3%, yield 91%;

[0038] The mass of the anion resin in step 1 is 10 grams;

[0039] The mass of o-hydroxyacetophenone in step 2 is 100 g, and the mass of diethyl carbonate in step 2 is 200 g;

[0040] The reaction time in step 3 is 3 hours;

[0041] The stirring time in the step 4 is 30 minutes;

[0042] The temperature used for drying in step nine is 80°C;

[0043] The drying time in step nine is 4 hours.

[0044] The invention firstly puts 1000 milliliters of toluene into a 2000 milliliters four-necked bottle, then adds anion resin, stirs and dissolves, heats to 70°C, starts to drip a mixture of o-hydroxyacetophenone and diethyl carbonate, controls the dripping speed to drip slowly, and after the dripping is completed, keeps the temperature at 90°C for reaction, adds 1000 milliliters of water to dissolve the reaction material after the reaction is completed, stirs, separates layers, adjusts the pH of the water layer to 1-2 with HCL, precipitates the product, and filters to obtain a crude product. Weigh 200 grams of the crude product, dissolves it with 1000 milliliters of 70% ethanol, heats to 60°C, adds activated carbon for decolorization for 30 minutes, filters the activated carbon while hot, cools the ethanol solution to about 10°C, crystallizes and centrifuges to obtain the product, dries the product, detects HPLC content of 99.3%, and has a yield of 91%. The mass of the anion resin in step 1 is 10 grams, the mass of the o-hydroxyacetophenone in step 2 is 100 grams, the mass of the diethyl carbonate in step 2 is 200 grams, the reaction time in step 3 is 3 hours, the stirring time in step 4 is 30 minutes, the temperature used for drying in step 9 is 80° C., and the drying time in step 9 is 4 hours. The present invention uses o-hydroxyacetophenone and diethyl carbonate as raw materials, and the final product 4-hydroxycoumarin can be obtained by the next reaction of the anion exchange resin, so that the anion exchange resin can completely replace the organic base as a catalyst, can be repeatedly used 10 times without affecting the yield, greatly reduces the cost, reduces the use of acid and alkali, greatly reduces the three wastes, has a safe process, meets the yield standard, meets the product quality standard, has a cost advantage, and meets the production conditions.

[0045] Finally: The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 4-hydroxycoumarin, characterized in that: The following steps are involved: Step 1: Add 1000 ml of toluene into a 2000 ml four-necked bottle, then add anion resin and stir to dissolve; Step 2: Raise the temperature to 70°C, start dropping a mixture of o-hydroxyacetophenone and diethyl carbonate, and slowly drop by dropping at a controlled speed; Step 3: After the addition is complete, maintain the temperature at 90°C for reaction; Step 4: After the reaction is completed, add 1000 ml of water to dissolve the reaction material and stir; Step 5: Separate the layers, adjust the pH of the aqueous layer to 1-2 with HCL, and the product precipitates; Step 6: Filter to obtain a crude product; Step 7: Weigh 200 g of the crude product, dissolve it in 1000 ml of 70% ethanol, raise the temperature to 60°C, add activated carbon for decolorization for 30 minutes, and filter the activated carbon while it is hot; Step 8: Cooling the ethanol solution to about 10°C, and centrifuging to obtain the product; Step 9: Dry the product; Step 10: HPLC content detection 99.3%, yield 91%.

2. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The mass of the anion resin in step 1 is 10 grams.

3. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The mass of o-hydroxyacetophenone in the step 2 is 100 g, and the mass of diethyl carbonate in the step 2 is 200 g.

4. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The reaction time in step 3 is 3 hours.

5. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The stirring time in the step 4 is 30 minutes.

6. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The temperature used for drying in step nine is 80°C.

7. A method for synthesizing 4-hydroxycoumarin according to claim 1, characterized in that: The drying time in step nine is 4 hours.

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