Preparation method of high-purity neohesperidin dihydrochalcone crystal
By optimizing the preparation method of neohesperidin dihydrochalcone, and employing alkaline solution dissolution, low-temperature crystallization, and recrystallization techniques, the problem of low purity of neohesperidin dihydrochalcone was solved, achieving the effect of high sweetness and long-lasting sweetness of high-purity crystals.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ANHUI JINHE SYNTHETIC MATERIAL RESEARCH INSTITUTE CO LTD
- Filing Date
- 2025-12-10
- Publication Date
- 2026-05-12
AI Technical Summary
The purity of neohesperidin dihydrochalcone in the existing technology is low, resulting in poor sweetness and a bitter aftertaste, which affects product quality.
High-purity neohesperidin dihydrochalcone crystals were prepared by pretreatment of neohesperidin and optimization of crystallization solvent selection, followed by alkaline solution dissolution, low-temperature crystallization, precipitation in alcohol solvent, and recrystallization.
It improves the purity of neohesperidin dihydrochalcone, resulting in higher sweetness, longer sweetness retention, richer sweetness, and a longer aftertaste, overcoming the problems of low purity and impurities in traditional methods.
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Figure CN122011060A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of sweetener technology, and in particular to a method for preparing high-purity neohesperidin dihydrochalcone crystals. Background Technology
[0002] Neohesperidin dihydrochalcone is a green food additive derived from the biotransformation or chemical processing of the natural citrus components neohesperidin or naringin. Its sweetness is 1500-1800 times that of sucrose, with a slow-release, long-lasting sweetness, good stability, non-toxicity, and rapid metabolism. When used in combination with sucralose, maltol, etc., it exhibits good synergistic effects, providing sweetening, aroma, flavor enhancement, and masking of bitterness. In carbonated beverages, it can improve sourness, astringency, and unpleasant aftertaste, and can be used as a flavor enhancer and taste corrector. It has extremely low caloric value, strong antioxidant properties, and anti-inflammatory, hypoglycemic, lipid-lowering, and hepatoprotective activities, making it widely applicable. Neohesperidin dihydrochalcone is a very safe sweetener.
[0003]
[0004] Currently, the main method for preparing neohesperidin dihydrochalcone involves the hydrogenation reduction of neohesperidin in an alkaline aqueous solution using a catalyst. The catalyst plays a crucial role in this reaction; both palladium on carbon and nickel skeleton can be used, but palladium on carbon is more effective than nickel skeleton. The amount of catalyst used and the number of times it is applied directly affect the yield of neohesperidin dihydrochalcone. Xiao Lekuo (Study on the process of synthesizing neohesperidin dihydrochalcone[J]. Guangdong Chemical Industry, 2014, 12(12): 55-56.), Lei Jia (Optimization of the synthesis process of neohesperidin dihydrochalcone[J]. Food Science and Technology, 2014, 12(39): 278-280.), Xu Guobo (Study on the process of synthesizing neohesperidin dihydrochalcone at room temperature and pressure[J]. Journal of Beijing Chemical Industry and Chemistry, 2010, 5(37): 111-114.) et al. have discussed in detail the catalyst types, temperature, pressure, solvents and processes for synthesizing neohesperidin dihydrochalcone.
[0005] Neohesperidin, the primary raw material for the preparation of neohesperidin dihydrochalcone, is currently prepared mainly through natural extraction, chemical synthesis of neohesperidin using naringin, and bio-fermentation. Naturally extracted neohesperidin is mainly found in plants such as trifoliate orange and citrus. The content of neohesperidin gradually decreases as the fruit matures; therefore, young fruit is often harvested for extraction. Neohesperidin accounts for 3%–5% of the fresh weight of young fruit. Furthermore, trifoliate orange is a perennial plant, requiring 3–5 years to reach full production, resulting in a supply shortage. Chemical synthesis and bio-fermentation of naringin involve processes such as conversion and purification, which may introduce impurities such as naringin.
[0006] In the traditional process for preparing neohesperidin dihydrochalcone, the low purity of the neohesperidin raw material and process impurities generated during synthesis result in low purity of the product, which is generally a white powder. These impurities not only affect the crystal form of neohesperidin dihydrochalcone but also its sweetness, leading to a pronounced bitter aftertaste. Summary of the Invention
[0007] To address the aforementioned problems, this invention provides a method for preparing high-purity neohesperidin dihydrochalcone, along with its crystal form and sweetness evaluation. This method employs neohesperidin pretreatment and optimizes the selection of crystallization solvents for neohesperidin dihydrochalcone to synthesize high-purity neohesperidin dihydrochalcone. Furthermore, needle-like crystals of neohesperidin dihydrochalcone are obtained, exhibiting high sweetness, long-lasting sweetness, high sweetness abundance, and a long-lasting aftertaste.
[0008] To achieve the above objectives, the present invention adopts the following technical solution, comprising the following steps:
[0009] S1. Neohesperidin raw material is dissolved in an alkaline solution. After complete dissolution, acid and alcohol solvents are added at room temperature, followed by low-temperature crystallization, filtration and drying to obtain high-purity neohesperidin.
[0010] S2. Neohesperidin is converted into neohesperidin dihydrochalcone in the presence of alkaline solution, hydrogen, palladium on carbon or Raney nickel. The pH is adjusted to 3-6, alcohol is added as a mixed solvent, and high-purity neohesperidin dihydrochalcone is obtained by precipitation at room temperature.
[0011] S3. High-purity neohesperidin dihydrochalcone was recrystallized with alcohol / methyl tertiary ether to obtain neohesperidin dihydrochalcone crystals.
[0012] Preferably, in the above method, in step S1, the alkaline solution used for purifying neohesperidin is an aqueous solution of triethylamine, potassium carbonate, sodium carbonate, sodium hydroxide, or potassium hydroxide, with a concentration of 10-30%, and the mass ratio of neohesperidin to the alkaline solution is 1:2-6.
[0013] Preferably, in the above method, in step S1, the acid used for purifying neohesperidin is a common acid such as hydrochloric acid, sulfuric acid, or phosphoric acid, and the molar ratio of acid to alkaline solution is 1:0.9~2.5.
[0014] Preferably, in the above method, in step S1, the alcohol solvent used for purifying neohesperidin is methanol, ethanol, or isopropanol, and the mass ratio of neohesperidin to the alcohol solvent is 1:4~10.
[0015] Preferably, in the above method, step S2 employs a one-pot synthesis of neohesperidin. The alkaline solution is a 5%~20% (w / w) aqueous solution of sodium hydroxide or potassium hydroxide. The mass ratio of palladium on carbon or Raney nickel to neohesperidin is 1:5~20, the mass ratio of neohesperidin to alkaline solution is 1:4~20, the reaction temperature is 20~40℃, the pressure is 0.5~3.0 MPa, and the reaction time is 10~15 hours.
[0016] Preferably, in the above method, in step S3, the alcohol is methanol, ethanol, or isopropanol.
[0017] Preferably, in the above method, in step S3, the alcohol is methanol, ethanol, or isopropanol, and the mass ratio of the alcohol to methyl tert-butyl ether is 1:0.5~1.5.
[0018] The present invention has the following beneficial effects:
[0019] This invention relates to the preparation of high-purity neohesperidin dihydrochalcone and its sweetness evaluation. Neohesperidin is recrystallized to remove impurities such as naringin and hesperidin that affect product purity, thereby improving the purity of the raw materials and thus increasing the purity of neohesperidin dihydrochalcone. After recrystallization, high-purity neohesperidin dihydrochalcone is obtained as needle-like crystals, which have high sweetness, long-lasting sweetness, high sweetness abundance, and a long aftertaste. Attached Figure Description
[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0021] Figure 1 This is the liquid chromatogram of sample 1 in Comparative Example 1 of the present invention;
[0022] Figure 2 This is the liquid chromatogram of sample 2 in Comparative Example 2 of the present invention;
[0023] Figure 3 This is the liquid chromatogram of sample 3 in Example 1 of the present invention;
[0024] Figure 4 This is a high-powered microscope image of the needle-shaped crystal in Embodiment 1 of the present invention. Detailed Implementation
[0025] The technical solutions in the embodiments will be clearly and completely described below.
[0026] I. Synthesis of high-purity neohesperidin dihydrochalcone
[0027] Comparative Example 1
[0028] Neohesperidin (30 g), palladium on carbon (3 g), and 10% sodium hydroxide (300 g) were weighed into a hydrogenation reactor. Hydrogen gas was introduced to 2.0 MPa, and the reaction was carried out at room temperature for 12 hours. After the reaction was completed, the catalyst was separated by vacuum filtration. The mother liquor was adjusted to pH 6 with hydrochloric acid, and allowed to stand for 6 hours to crystallize. After filtration, the solid was dried under vacuum for 8 hours to obtain neohesperidin dihydrochalcone.
[0029] According to liquid chromatography (LC) analysis, the yield of the new hesperidin dihydrochalcone catalyzed in this embodiment was 92%, and the purity was 96.7%, which is recorded as sample 1.
[0030] Comparative Example 2
[0031] Neohesperidin (30 g), Raney nickel (4 g), and 10% sodium hydroxide (300 g) were weighed into a hydrogenation reactor. Hydrogen gas was introduced to a pressure of 2.0 MPa, and the reaction was carried out at room temperature for 12 hours. After the reaction was completed, the mixture was filtered, and hydrochloric acid was added to adjust the pH to 6. Ethanol (20 g) was added, and the mixture was allowed to stand for 6 hours to crystallize. After filtration, the solid was dried under vacuum for 8 hours to obtain neohesperidin dihydrochalcone.
[0032] According to liquid chromatography (LC) analysis, the yield of the new hesperidin dihydrochalcone catalyzed in this embodiment was 90%, and the purity was 98.0%, which is recorded as sample 2.
[0033] Example 1
[0034] Weigh 100 g of neohesperidin, dissolve it in 5 g of 15% sodium hydroxide, add 260 g of ethanol and 1.9 g of hydrochloric acid, cool to 0°C and crystallize for 2 hours. Dry the solid under vacuum to obtain high-purity neohesperidin. Weigh the purified neohesperidin, add 30 g of neohesperidin, 3 g of palladium on carbon, and 300 g of 10% sodium hydroxide in a hydrogenation reactor, purge with hydrogen gas, and react at room temperature for 12 hours. After the reaction, filter, add hydrochloric acid to adjust the pH to 5, add 20 g of ethanol, let stand for 6 hours to crystallize, and filter.
[0035] Recrystallization: Weigh 5 g of neohesperidin dihydrochalcone into a flask, add 30 g of ethanol, and after complete dissolution, add 20 g of methyl tert-butyl ether. Let stand for 6 hours to recrystallize, filter, and dry the solid under vacuum for 8 hours to obtain neohesperidin dihydrochalcone.
[0036] According to liquid chromatography (LC) analysis, the yield of the new hesperidin dihydrochalcone catalyzed in this embodiment was 95%, and the purity was 99.3%, which is recorded as sample 3.
[0037] II. Evaluation of the crystal form of neohesperidin dihydrochalcone
[0038] In section I above, the novel hesperidin dihydrochalcone prepared in Comparative Examples 1-2 and Example 1 is designated as Sample 1, 2, and 3, respectively. Two other commercially available novel hesperidin dihydrochalcones were purchased and designated as Sample 4 and 5, respectively. Sample 3 consists of needle-like crystals. A high-power microscope image of the needle-like crystals is shown below. Figure 4 As shown.
[0039] III. Sweetness Evaluation of Neohesperidin Dihydrochalcone
[0040] Sweetness is a crucial property of sweeteners, enhancing food flavor and influencing our food preferences. The intensity of sweetness is expressed as sweetness degree, typically measured using a sucrose aqueous solution at 20°C with a sweetness level of 1.0 as a benchmark. The sweetness of other substances is then compared to this benchmark. A 0.5% standard comparison solution of sucrose was prepared. Samples 1-5 were dissolved in water, and the concentration was continuously varied while the sample solutions and the standard comparison solution were tasted and compared until the sweetness of the sample at a specific concentration was exactly the same as that of the standard sucrose comparison solution. To avoid bias due to individual taste differences, the sweetness was evaluated by three professional evaluators, and the average value was taken. The evaluation results are shown in Table 1 below.
[0041] Table 1: Sweetness Evaluation Results
[0042] serial number Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sweetness 1740 1880 2050 1830 1720
[0043] The taste of neohesperidin dihydrochalcone was also evaluated, mainly from the aspects of the speed of sweetness presentation, initial sweetness, sweetness abundance, aftertaste, duration of sweetness, and whether there is bitterness. The overall liking level is out of 10. The average score was taken after three professional taste testers. The results are shown in Table 2.
[0044] Table 2: Taste Evaluation Results
[0045] serial number level of liking Overall taste description Sample 1 7.5 It has a slightly stronger initial sweetness, a medium sweetness level, and a relatively short duration of sweetness. Sample 2 8.7 The sweetness lasts a long time, has a high sweetness richness, and leaves a bitter aftertaste. Sample 3 9.5 It has a long-lasting sweetness, a high sweetness content, and a long aftertaste. Sample 4 8.8 It has a slightly stronger initial sweetness, a higher overall sweetness level, and a moderate lingering aftertaste. Sample 5 7.8 Medium sweetness, short-lived sweetness, with a lingering bitterness.
[0046] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any modifications, equivalent substitutions, and improvements made by those skilled in the art to the above embodiments without departing from the scope of the technical solution of the present invention, based on the technical essence of the present invention, shall still fall within the protection scope of the technical solution of the present invention.
Claims
1. A method for preparing high-purity neohesperidin dihydrochalcone crystals, characterized in that, Includes the following steps: S1. Neohesperidin raw material is dissolved in an alkaline solution. After complete dissolution, acid and alcohol solvents are added at room temperature, followed by low-temperature crystallization, filtration and drying to obtain high-purity neohesperidin. S2. High-purity neohesperidin is converted into neohesperidin dihydrochalcone in the presence of alkaline solution, hydrogen, palladium on carbon or Raney nickel. The pH is adjusted to 3-6, alcohol is added as a mixed solvent, and high-purity neohesperidin dihydrochalcone is obtained by precipitation at room temperature. S3. High-purity neohesperidin dihydrochalcone was recrystallized from alcohol / methyl tert-butyl ether to obtain neohesperidin dihydrochalcone crystals.
2. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S1, the alkaline solution used for the purification of neohesperidin is an aqueous solution of triethylamine, potassium carbonate, sodium carbonate, sodium hydroxide, or potassium hydroxide, with a concentration of 10-30%, and the mass ratio of neohesperidin to the alkaline solution is 1:2-6.
3. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S1, the acid used for the purification of neohesperidin is hydrochloric acid, sulfuric acid, or phosphoric acid, and the molar ratio of acid to alkaline solution is 1:0.9~2.
5.
4. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S1, the alcohol solvent used for the purification of neohesperidin is methanol, ethanol, or isopropanol, and the mass ratio of neohesperidin to alcohol solvent is 1:4~10.
5. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S2, a one-pot method is used to synthesize the new hesperidin, and the alkaline solution is a 5%~20% sodium hydroxide or potassium hydroxide aqueous solution.
6. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S2, the mass ratio of palladium on carbon or Raney nickel to neohesperidin is 1:5~20.
7. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S2, the mass ratio of high-purity neohesperidin to alkaline solution is 1:4~20.
8. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S2, the reaction temperature is 20~40℃, the pressure is 0.5~3.0 MPa, and the reaction time is 10~15 hours.
9. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S2, the alcohol is methanol, ethanol, or isopropanol.
10. The method for preparing high-purity neohesperidin dihydrochalcone crystals according to claim 1, characterized in that: In step S3, the alcohol is methanol, ethanol, or isopropanol, and the mass ratio of alcohol to methyl tert-butyl ether is 1:0.5~1.5.