A method for preparing root bark acetylphenyl-4'-β-neohesperidin

Abstract

This invention discloses a method for preparing naringin-4'-β-neohesperidin from root bark, belonging to the field of organic chemical synthesis technology. This preparation method can hydrolyze naringin at a lower temperature to generate naringin-4'-β-neohesperidin from root bark. The whole process has few side reactions, high product yield, and less environmental pollution. The method includes the following steps: (1) Dissolving naringin in an ethanol aqueous solution; (2) Adding potassium hydroxide-supported alumina to the solution obtained in step (1) and heating to react; (3) Filtering the reaction solution obtained in step (2) and concentrating the filtrate until there is no ethanol in the solution; (4) Cooling the concentrated solution obtained in step (3) and allowing it to stand to crystallize; (5) Filtering the crystals obtained in step (4), washing with water and drying to obtain the finished product.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis technology, and more specifically, to a method for preparing root bark acetylphenyl-4'-β-neohesperidin. Background Technology

[0002] Naringin belongs to the natural flavonoid class of compounds and is a raw material for the industrial synthesis of neohesperidin dihydrochalcone. The synthesis of neohesperidin dihydrochalcone from naringin involves three steps: first, the preparation of root bark acetylphenyl-4'-β-neohesperidin; second, the preparation of neohesperidin; and third, the preparation of neohesperidin dihydrochalcone. Current methods for preparing root bark acetylphenyl-4'-β-neohesperidin include the following steps: dissolving naringin in an aqueous potassium hydroxide solution; after complete dissolution, heating the solution; stopping the reaction after a period of time; diluting with an equal volume of water; cooling to room temperature; adjusting the pH to approximately 6.0 with hydrochloric acid; heating to above 75°C to dissolve the precipitate; cooling to room temperature to crystallize; filtering under reduced pressure; and vacuum drying to obtain the crude product. The crude product is then dissolved in water with a pH of approximately 6.0 and heated to above 75°C, cooled to room temperature to crystallize, filtered, and the process is repeated three times to obtain the final product.

[0003] The existing method for preparing naringin from root bark acetylphenyl-4'-β-neohesperidin uses water as a solvent and potassium hydroxide as a catalyst, dissolving naringin and then hydrolyzing it under high temperature and strong alkaline conditions. However, under these conditions, the reaction produces a large number of byproducts, resulting in a low yield, with a maximum yield of 70%. Furthermore, the reaction uses large amounts of acid and alkali, which pollutes the environment. Therefore, improving the yield of naringin from root bark acetylphenyl-4'-β-neohesperidin to obtain more neohesperidin dihydrochalcone is a new direction for future research. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing root bark acetylphenyl-4'-β-neohesperidin. This method can hydrolyze naringin at a lower temperature to generate root bark acetylphenyl-4'-β-neohesperidin. The whole process generates few side reactions, has a high yield of the finished product, and causes less environmental pollution.

[0005] The technical solution of this invention is as follows:

[0006] A method for preparing root bark acetylphenyl-4'-β-neohesperidin includes the following steps:

[0007] (1) Dissolve naringin in an ethanol aqueous solution;

[0008] (2) Add potassium hydroxide-supported alumina to the solution obtained in step (1) and heat to react;

[0009] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution;

[0010] (4) Cool the concentrated solution obtained in step (3) and let it stand to crystallize;

[0011] (5) The crystals obtained in step (4) are filtered, washed with water and dried to obtain the finished product.

[0012] Furthermore, in step (1), the concentration of the ethanol aqueous solution is 40-60%, and the mass ratio of the added naringin to the volume of the ethanol aqueous solution is 1:10-20.

[0013] Furthermore, in step (2), the mass ratio of potassium hydroxide-supported alumina to naringin is 0.02 to 0.1:1, the solution is heated to 40 to 70°C, and the reaction time is 4 to 8 hours.

[0014] Furthermore, in step (4), the concentrated solution obtained in step (3) is cooled to 5-10°C and allowed to stand for crystallization for 5-10 hours.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0016] In a method for preparing naringin from root bark acetylphenyl-4'-β-neohesperidin according to the present invention, naringin is dissolved in an ethanol-water solution; potassium hydroxide-supported alumina is added to the solution, and the reaction is carried out by heating; the reaction solution is filtered, and the filtrate is concentrated until no ethanol remains in the solution; the solution is cooled and allowed to stand to crystallize; the solution is filtered, washed with water, and dried to obtain the finished product. By using solid potassium hydroxide-supported alumina instead of the traditional liquid alkali, naringin can be hydrolyzed at a lower temperature to generate naringin-4'-β-neohesperidin. The reaction temperature of the entire process is 40–70°C. Although the reaction time is slightly longer, the reaction is carried out under more controllable conditions, making it more stable and safer, with fewer side reactions. This results in a higher product yield and reduces the amount of acid and alkali used in the reaction process, thus reducing environmental pollution. Detailed Implementation

[0017] The technical solution of the present invention will be further described in detail below with reference to specific embodiments, but this does not constitute any limitation on the present invention.

[0018] A method for preparing root bark acetylphenyl-4'-β-neohesperidin includes the following steps:

[0019] (1) Dissolve naringin in an ethanol aqueous solution. The concentration of the ethanol aqueous solution is 40-60%, and the mass ratio of the added naringin to the volume of the ethanol aqueous solution is 1:10-20.

[0020] (2) Add potassium hydroxide-supported alumina to the solution obtained in step (1) and heat to react. The mass ratio of potassium hydroxide-supported alumina to naringin is 0.02 to 0.1:1. The solution is heated to 40 to 70°C and the reaction time is 4 to 8 hours.

[0021] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0022] (4) Cool the concentrated solution obtained in step (3) and let it stand to crystallize. The concentrated solution is cooled to 5-10°C and allowed to stand for crystallization for 5-10 hours.

[0023] (5) The crystals obtained in step (4) are filtered, washed with water and dried to obtain the finished product.

[0024] In the preparation method of this invention, naringin is dissolved in an ethanol aqueous solution, and solid potassium hydroxide-supported alumina is used instead of traditional liquid alkali, so that naringin can be hydrolyzed at a lower temperature to generate root bark acetylphenyl-4'-β-neohesperidin. The reaction temperature of the whole process is 40-70°C. Although the reaction time is extended, the reaction is carried out under more controllable conditions, making it more stable and safe, with very few side reactions. This improves the product yield and reduces the amount of acid and alkali used in the reaction process, thus reducing environmental pollution.

[0025] Example 1

[0026] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0027] (1) Dissolve 100g of naringin in 2000mL of 40% ethanol aqueous solution.

[0028] (2) Add 10g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 70°C and react for 4 hours.

[0029] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0030] (4) Cool the concentrated solution obtained in step (3) to 5°C and let it stand for 5 hours to crystallize.

[0031] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.7% and the yield was 90.19%.

[0032] Example 2

[0033] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0034] (1) Dissolve 100g of naringin in 1500mL of 50% ethanol aqueous solution.

[0035] (2) Add 5g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 50°C and react for 5 hours.

[0036] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0037] (4) Cool the concentrated solution obtained in step (3) to 7°C and let it stand for 6 hours to crystallize.

[0038] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 76g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.5% and the yield was 91.21%.

[0039] Example 3

[0040] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0041] (1) Dissolve 100g of naringin in 1000mL of 60% ethanol aqueous solution.

[0042] (2) Add 2g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 70°C and react for 8 hours.

[0043] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0044] (4) Cool the concentrated solution obtained in step (3) to 6°C and let it stand for 10 hours to crystallize.

[0045] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75.6g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.9% and the yield was 91.09%.

[0046] Example 4

[0047] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0048] (1) Dissolve 100g of naringin in 1900mL of 40% ethanol aqueous solution.

[0049] (2) Add 9g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 40°C and react for 7 hours.

[0050] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0051] (4) Cool the concentrated solution obtained in step (3) to 7°C and let it stand for 6 hours to crystallize.

[0052] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 76.1g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.8% and the yield was 91.6%.

[0053] Example 5

[0054] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0055] (1) Dissolve 100g of naringin in 1200mL of 60% ethanol aqueous solution.

[0056] (2) Add 8g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 50°C and react for 6 hours.

[0057] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0058] (4) Cool the concentrated solution obtained in step (3) to 6°C and let it stand for 9 hours to crystallize.

[0059] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75.8g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.3% and the yield was 90.78%.

[0060] Example 6

[0061] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0062] (1) Dissolve 100g of naringin in 1100mL of 60% ethanol aqueous solution.

[0063] (2) Add 2g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 70°C and react for 8 hours.

[0064] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0065] (4) Cool the concentrated solution obtained in step (3) to 9°C and let it stand for 9 hours to crystallize.

[0066] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 76.4g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.9% and the yield was 92.06%.

[0067] Example 7

[0068] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0069] (1) Dissolve 100g of naringin in 1300mL of 60% ethanol aqueous solution.

[0070] (2) Add 5g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 60°C and react for 4 hours.

[0071] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0072] (4) Cool the concentrated solution obtained in step (3) to 8°C and let it stand for 8 hours to crystallize.

[0073] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 76.3g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.7% and the yield was 91.75%.

[0074] Example 8

[0075] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0076] (1) Dissolve 100g of naringin in 1800mL of 50% ethanol aqueous solution.

[0077] (2) Add 7g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 50°C and react for 7 hours.

[0078] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0079] (4) Cool the concentrated solution obtained in step (3) to 6°C and let it stand for 6 hours to crystallize.

[0080] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75.9g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.9% and the yield was 91.46%.

[0081] Example 9

[0082] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0083] (1) Dissolve 100g of naringin in 1700mL of 50% ethanol aqueous solution.

[0084] (2) Add 8g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 50°C and react for 6 hours.

[0085] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0086] (4) Cool the concentrated solution obtained in step (3) to 10°C and let it stand for 5 hours to crystallize.

[0087] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75.3g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 99.1% and the yield was 90.92%.

[0088] Example 10

[0089] A root bark acetylphenyl-4'-β-neohesperidin, the preparation process of which includes the following steps:

[0090] (1) Dissolve 100g of naringin in 1400mL of 50% ethanol aqueous solution.

[0091] (2) Add 6g of potassium hydroxide-supported alumina to the solution obtained in step (1), heat to 60°C and react for 8 hours.

[0092] (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution.

[0093] (4) Cool the concentrated solution obtained in step (3) to 9°C and let it stand for 5 hours to crystallize.

[0094] (5) The crystals obtained in step (4) were filtered, washed with water and dried to obtain 75.2g of root bark acetylphenyl-4'-β-neohesperidin. The purity of the liquid phase was determined to be 98.9% and the yield was 90.61%.

[0095] Comparative Example

[0096] The preparation of 4'-β-neohesperidin from root bark was carried out according to the existing preparation method. The process was as follows: 100g of naringin was dispersed in 1500mL of water, 225g of potassium hydroxide was added, and the mixture was heated to boiling and refluxed for 2 hours. After the reaction was completed, hydrochloric acid was added to adjust the pH of the solution to 6-7. The reaction solution was cooled and allowed to stand at 7℃ for 6 hours to crystallize. The solution was filtered, washed with water, and dried to obtain 53g of 4'-β-neohesperidin from root bark. The purity of the liquid phase was determined to be 95.6%, and the yield was 61.71%.

[0097] Based on the preparation process and the obtained root bark acetylphenyl-4'-β-neohesperidin of comparative examples and Examples 1-10, it can be seen that the root bark acetylphenyl-4'-β-neohesperidin prepared by the method of the present invention has higher liquid phase purity and recovery rate compared with the root bark acetylphenyl-4'-β-neohesperidin prepared by existing methods, and the amount of acid and alkali used in the reaction process is reduced, thus reducing environmental pollution.

[0098] The above description is only a preferred embodiment of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing root bark acetylphenyl-4'-β-neohesperidin, characterized in that, Includes the following steps: (1) Dissolve naringin in an ethanol aqueous solution; (2) Add potassium hydroxide-supported alumina to the solution obtained in step (1) and heat to react; (3) Filter the reaction solution obtained in step (2) and concentrate the filtrate until there is no ethanol in the solution; (4) Cool the concentrated solution obtained in step (3) and let it stand to crystallize; (5) The crystals obtained in step (4) are filtered, washed with water and dried to obtain the finished product.

2. The method for preparing acetylphenyl-4'-β-neohesperidin from root bark according to claim 1, characterized in that, In step (1), the concentration of the ethanol aqueous solution is 40-60%, and the mass ratio of the added naringin to the volume of the ethanol aqueous solution is 1:10-20.

3. The method for preparing root bark acetylphenyl-4'-β-neohesperidin according to claim 1 or 2, characterized in that, In step (2), the mass ratio of potassium hydroxide-supported alumina to naringin is 0.02 to 0.1:1, the solution is heated to 40 to 70°C, and the reaction time is 4 to 8 hours.

4. The method for preparing acetylphenyl-4'-β-neohesperidin from root bark according to claim 3, characterized in that, In step (4), the concentrated solution obtained in step (3) is cooled to 5-10°C and allowed to stand for crystallization for 5-10 hours.