A novel method for preparing hesperidin
By using n-butanol and 3-indoleacetic acid as catalysts in the preparation of neohesperidin, the problems of low purity and environmental pollution in existing technologies have been solved, and a safe and simple method for preparing high-purity neohesperidin has been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- GUILIN NATURAL INGREDIENTS CORP
- Filing Date
- 2022-10-12
- Publication Date
- 2026-05-26
AI Technical Summary
Existing methods for preparing hesperidin result in low purity, requiring further purification, and involve the use of reagents with irritating odors, which pollute the environment.
Using n-butanol as solvent and 3-indoleacetic acid as catalyst, acetylphenyl-4'-β-neohesperidin and isovandrin from root bark are reacted to generate neohesperidin. The reaction conditions are simple, and after cooling, the product is washed with n-butanol and dried to obtain a high-purity product.
This method enables the direct acquisition of high-purity neohesperidin under safe and environmentally friendly conditions, avoiding harsh conditions and the use of reagents with irritating odors, thus simplifying the preparation process.
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic chemical synthesis technology, and more specifically, to a method for preparing a novel hesperidin. Background Technology
[0002] Neohesperidin is an important dihydroflavonoid compound, primarily used in the synthesis of neohesperidin dihydrochalcone—a novel sweetener widely used in the food, pharmaceutical, and feed industries. It is mostly obtained through extraction, isolation, and synthesis from natural plants. The steps for preparing neohesperidin dihydrochalcone are: 1. Preparation of root bark acetylphenyl-4'-β-neohesperidin; 2. Preparation of neohesperidin; 3. Preparation of neohesperidin dihydrochalcone.
[0003] Existing methods for preparing neohesperidin mainly include extraction and synthesis. CN101863940B discloses a synthetic process for neohesperidin, which involves dissolving acetylphenyl-4'-β-neohesperidin from root bark in ethanol, adding proline as a catalyst and isovalin as a reactant, heating to reflux, stirring under reflux, and cooling and filtering after the reaction is complete. The resulting solid is washed with a large amount of water until it turns white, and then dried under vacuum at 60°C. CN 106432386B discloses a method for synthesizing neohesperidin from naringin as a raw material, which involves dissolving acetylphenyl-4'-β-neohesperidin from root bark in water or an organic solvent, adding isovalin and histidine, refluxing, and after the reaction is complete, freezing to crystallize, filtering, and drying to obtain crude neohesperidin; then dissolving it in a low-carbon alcohol aqueous solution by heating, cooling to crystallize, filtering, and drying the filter cake to obtain refined neohesperidin.
[0004] Existing methods for preparing neohesperidin generally use water or organic solvents as solvents and tetrahydropyrrole, proline, or histidine as catalysts. The resulting neohesperidin has low purity and requires further purification to obtain high-purity neohesperidin. Furthermore, the reaction uses reagents with irritating odors, polluting the environment. Therefore, improving the preparation method of neohesperidin to simplify the process and reduce the cost of this product is a new direction for future research. Summary of the Invention
[0005] The purpose of this invention is to provide a method for preparing a new hesperidin. This method has simple reaction conditions, is safe and environmentally friendly, and can obtain high-purity new hesperidin without purification after the reaction.
[0006] The technical solution of this invention is as follows:
[0007] A method for preparing a novel hesperidin includes the following steps:
[0008] (1) Take root bark acetylphenyl-4'-β-neohesperidin, add n-butanol, isovalin and 3-indoleacetic acid, and react after heating;
[0009] (2) Cool down the reaction solution after the reaction in step (1) is complete;
[0010] (3) Filter the cooled solution, wash the solid with n-butanol, and dry it to obtain the finished product.
[0011] Furthermore, in step (1), the volume ratio of added n-butanol, the mass of isovalanin, the mass of 3-indoleacetic acid, and the mass ratio of root bark acetylphenyl-4'-β-neohesperidin is 5-15:0.35-0.5:0.03-0.1:1.
[0012] Furthermore, in step (1), the temperature is raised to 80-110°C and the reaction time is 2-6 hours.
[0013] Furthermore, in step (2), the reaction solution obtained in step (2) is cooled to 10-30°C.
[0014] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0015] In a method for preparing a new hesperidin according to the present invention, 4'-β-neohesperidin from root bark is taken, and n-butanol, isovalin, and 3-indoleacetic acid are added. The mixture is heated and reacted, then cooled; filtered, the solid is washed with n-butanol, and dried to obtain the finished product. Using 4'-β-neohesperidin from root bark as the starting material, n-butanol as the solvent, and 3-indoleacetic acid as the catalyst, it reacts with isovalin to generate new hesperidin. The reaction conditions are simple; the solid obtained after cooling is washed with n-butanol and dried. It does not require harsh conditions such as anhydrous and oxygen-free environments, nor does it use reagents with strong irritating odors. It is safe and environmentally friendly, and high-purity new hesperidin can be obtained without purification after the reaction. Detailed Implementation
[0016] 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.
[0017] A method for preparing a novel hesperidin includes the following steps:
[0018] (1) Take root bark acetylphenyl-4'-β-neohesperidin, add n-butanol, isovandin, and 3-indoleacetic acid, and heat to react. The volume ratio of n-butanol, the mass of isovandin, the mass of 3-indoleacetic acid, and the mass ratio of root bark acetylphenyl-4'-β-neohesperidin is 5–15:0.35–0.5:0.03–0.1:1. Heat to 80–110℃ and react for 2–6 hours.
[0019] (2) Cool down the reaction solution obtained in step (1) after it has reacted completely. Specifically, cool the reaction solution obtained in step (2) to 10-30°C.
[0020] (3) Filter the cooled solution, wash the solid with n-butanol, and dry it to obtain the finished product.
[0021] In the preparation method of this invention, acetylphenyl-4'-β-neohesperidin from root bark is used as the starting material, n-butanol is used as the solvent, and 3-indoleacetic acid is used as the catalyst to react with isovandrin to generate neohesperidin. The reaction conditions are simple. After cooling, the fixed product is washed and dried with n-butanol. It does not require harsh conditions such as anhydrous and oxygen-free environments, and does not use reagents with strong irritating odors. It is safe and environmentally friendly. After the reaction, high-purity neohesperidin can be obtained without purification.
[0022] Example 1
[0023] A novel hesperidin is prepared by the following steps:
[0024] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 500mL of n-butanol, 35g of isovalin and 3g of 3-indoleacetic acid, heat to 110℃ and react for 4 hours.
[0025] (2) After the reaction solution in step (1) has reacted completely, cool it down to 10°C.
[0026] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 122.1 g of neohesperidin. The purity of the liquid phase was determined to be 99.5% and the yield was 94.75%.
[0027] Example 2
[0028] A novel hesperidin is prepared by the following steps:
[0029] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 1000mL of n-butanol, 35g of isovalin and 5g of 3-indoleacetic acid, heat to 100℃ and react for 3 hours.
[0030] (2) After the reaction solution in step (1) has reacted completely, cool it down to 20°C.
[0031] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 121.5g of neohesperidin. The purity of the liquid phase was determined to be 99.3% and the yield was 94.09%.
[0032] Example 3
[0033] A novel hesperidin is prepared by the following steps:
[0034] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 1500mL of n-butanol, 50g of isovalin and 10g of 3-indoleacetic acid, heat to 80℃ and react for 6 hours.
[0035] (2) After the reaction solution in step (1) has reacted completely, cool it down to 20°C.
[0036] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 120.6 g of neohesperidin. The purity of the liquid phase was determined to be 99.4% and the yield was 93.49%.
[0037] Example 4
[0038] A novel hesperidin is prepared by the following steps:
[0039] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 1400mL of n-butanol, 45g of isovalin and 9g of 3-indoleacetic acid, heat to 90℃ and react for 5 hours.
[0040] (2) After the reaction solution in step (1) has reacted completely, cool it down to 30°C.
[0041] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 120.2g of neohesperidin. The purity of the liquid phase was determined to be 99.6% and the yield was 93.34%.
[0042] Example 5
[0043] A novel hesperidin is prepared by the following steps:
[0044] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 600mL of n-butanol, 35g of isovalin and 4g of 3-indoleacetic acid, heat to 90℃ and react for 3 hours.
[0045] (2) After the reaction solution in step (1) has reacted completely, cool it down to 10°C.
[0046] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 122g of neohesperidin. The purity of the liquid phase was determined to be 99.5% and the yield was 94.67%.
[0047] Example 6
[0048] A novel hesperidin is prepared by the following steps:
[0049] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 700mL of n-butanol, 40g of isovalin and 4g of 3-indoleacetic acid, heat to 90℃ and react for 5 hours.
[0050] (2) After the reaction solution in step (1) has reacted completely, cool it down to 20°C.
[0051] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 121.7g of neohesperidin. The purity of the liquid phase was determined to be 99.7% and the yield was 94.63%.
[0052] Example 7
[0053] A novel hesperidin is prepared by the following steps:
[0054] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 1200mL of n-butanol, 40g of isovalin and 7g of 3-indoleacetic acid, heat to 100℃ and react for 3 hours.
[0055] (2) After the reaction solution in step (1) has reacted completely, cool it down to 10°C.
[0056] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 120.8 g of neohesperidin. The purity of the liquid phase was determined to be 99.5% and the yield was 93.74%.
[0057] Example 8
[0058] A novel hesperidin is prepared by the following steps:
[0059] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 1100mL of n-butanol, 40g of isovalin and 6g of 3-indoleacetic acid, heat to 110℃ and react for 2 hours.
[0060] (2) After the reaction solution in step (1) has reacted completely, cool it down to 30°C.
[0061] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 121.6 g of neohesperidin. The purity of the liquid phase was determined to be 99.3% and the yield was 94.17%.
[0062] Example 9
[0063] A novel hesperidin is prepared by the following steps:
[0064] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 800mL of n-butanol, 35g of isovalin and 3g of 3-indoleacetic acid, heat to 110℃ and react for 3 hours.
[0065] (2) After the reaction solution in step (1) has reacted completely, cool it down to 20°C.
[0066] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 120.8 g of neohesperidin. The purity of the liquid phase was determined to be 99.8% and the yield was 94.02%.
[0067] Example 10
[0068] A novel hesperidin is prepared by the following steps:
[0069] (1) Take 100g of root bark acetylphenyl-4'-β-neohesperidin, add 900mL of n-butanol, 35g of isovalin and 4g of 3-indoleacetic acid, heat to 100℃ and react for 4 hours.
[0070] (2) After the reaction solution in step (1) has reacted completely, cool it down to 10°C.
[0071] (3) The cooled solution was filtered, the solid was washed with n-butanol and dried to obtain 121.8 g of neohesperidin. The purity of the liquid phase was determined to be 99.6% and the yield was 94.61%.
[0072] Based on the preparation process and the obtained neohesperidin in Examples 1-10, it can be seen that the neohesperidin prepared by the method of the present invention, compared with the neohesperidin prepared by existing methods, does not require harsh conditions such as anhydrous and oxygen-free conditions, does not use reagents with strong irritating odors, is safe and environmentally friendly, and can obtain high-purity neohesperidin without purification after the reaction, and the preparation process is simple.
[0073] 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 neohesperidin, characterized by, Includes the following steps: (1) Take root bark acetylphenyl-4'-β-neohesperidin, add n-butanol, isovalin and 3-indoleacetic acid, and react after heating; (2) Cool down the reaction solution after the reaction in step (1) is complete; (3) Filter the cooled solution, wash the solid with n-butanol, and dry it to obtain the finished product.
2. The method of preparing neohesperidin according to claim 1, characterized in that, In step (1), the volume ratio of added n-butanol, the mass of isovalanin, the mass of 3-indoleacetic acid, and the mass ratio of root bark acetylphenyl-4'-β-neohesperidin is 5-15:0.35-0.5:0.03-0.1:
1.
3. The method for preparing a new hesperidin according to claim 1 or 2, characterized in that, In step (1), the temperature is heated to 80-110°C and the reaction time is 2-6 hours.
4. The method for preparing a novel hesperidin according to claim 3, characterized in that, In step (2), the reaction solution obtained in step (2) is cooled to 10-30°C.