阅读说明：本技术 一种从柚皮素合成根皮素的方法 (Method for synthesizing phloretin from naringenin ) 是由 郭文华 肖金霞 赵景辉 于 2021-01-25 设计创作，主要内容包括：本发明涉及根皮素合成技术,具体涉及一种从柚皮素合成根皮素的方法,以解决现有在根皮素合成过程中,存在合成工艺路线复杂、产率低、副反应多,以及成本高的问题。本发明所采用的技术方案为：一种从柚皮素合成根皮素的方法,包括以下步骤：步骤1)将原料柚皮素溶解在质量浓度为4-6％的氢氧化钠乙醇溶液中,再加入三元镍催化剂,搅拌均匀后,升温至40-45℃,在0.8Mpa氢气压力下进行加氢反应,液相监控反应至反应液中原料柚皮素含量小于0.65-1％时停止反应,得到含有根皮素的乙醇溶液；步骤2)将催化剂去除,并调节含有根皮素的乙醇溶液的pH值到5-6；步骤3)将反应液浓缩回收,使乙醇至无醇后,加入纯化水冷却至室温,抽滤并烘干得到根皮素。(The invention relates to a phloretin synthesis technology, in particular to a method for synthesizing phloretin from naringenin, which solves the problems of complex synthesis process route, low yield, more side reactions and high cost in the conventional phloretin synthesis process. The technical scheme adopted by the invention is as follows: a method for synthesizing phloretin from naringenin, comprising the following steps: step 1) dissolving a raw material naringenin in a sodium hydroxide ethanol solution with the mass concentration of 4-6%, adding a ternary nickel catalyst, uniformly stirring, heating to 40-45 ℃, carrying out hydrogenation reaction under the hydrogen pressure of 0.8Mpa, and stopping the reaction when the content of the raw material naringenin in a reaction solution is less than 0.65-1% by liquid phase monitoring reaction to obtain an ethanol solution containing the naringenin; step 2) removing the catalyst, and adjusting the pH value of the phloretin-containing ethanol solution to 5-6; and 3) concentrating and recovering the reaction liquid, adding purified water to cool the ethanol until no ethanol exists, carrying out suction filtration, and drying to obtain phloretin.)

1. A method for synthesizing phloretin from naringenin is characterized by comprising the following steps:

step 1) dissolving a raw material naringenin in a sodium hydroxide ethanol solution with the mass concentration of 4-6%, adding a ternary nickel catalyst, uniformly stirring, heating to 40-45 ℃, carrying out hydrogenation reaction under the hydrogen pressure of 0.8Mpa, and stopping the reaction when the content of the raw material naringenin in a reaction solution is less than 0.65-1% by liquid phase monitoring reaction to obtain an ethanol solution containing the naringenin;

step 2) removing the catalyst in the alcohol solution containing the phloretin, and adjusting the pH value of the alcohol solution containing the phloretin to 5-6;

and 3) concentrating and recovering the reaction liquid treated in the step 2), adding purified water to cool the ethanol until no ethanol exists, filtering and drying to obtain phloretin.

2. The method of claim 1, wherein the step of synthesizing phloretin from naringenin comprises: in the step 1), the mass ratio of the naringenin to the sodium hydroxide ethanol solution is 1: 10.

3. The method for synthesizing phloretin from naringenin according to claim 1 or 2, wherein: in the step 1), the addition amount of the ternary nickel catalyst is 7% of the mass of the raw material naringenin.

4. The method of claim 3, wherein the step of synthesizing phloretin from naringenin comprises: in the step 1), the hydrogenation reaction is carried out for 3-3.5 h.

5. The method of claim 4, wherein the step of synthesizing phloretin from naringenin comprises: in the step 3), the mass ratio of the purified water to the raw material naringenin is 1: 2.

6. The method of claim 5, wherein the step of synthesizing phloretin from naringenin comprises: in the step 2), the solvent for adjusting the pH value of the phloretin-containing ethanol solution is hydrochloric acid.

7. The method for synthesizing phloretin from naringenin according to claim 1 or 2, wherein: the specific steps of the step 1) are as follows: dissolving 300g of raw material naringenin in 3000g of 6% sodium hydroxide ethanol solution, uniformly stirring, heating to 45 ℃, carrying out hydrogenation reaction for 3.5h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the liquid phase controlled reaction solution is less than 0.88% to obtain the ethanol solution containing the naringenin.

8. The method for synthesizing phloretin from naringenin according to claim 1 or 2, wherein: the specific steps of step 3) are: concentrating and recovering the reaction liquid treated in the step 2), adding 600g of purified water to cool to room temperature after ethanol is removed, carrying out suction filtration and drying to obtain phloretin.

Technical Field

The invention relates to a phloretin synthesis technology, in particular to a method for synthesizing phloretin from naringenin.

Background

Phloretin (Phloretin), known under the name 2, 4, 6-trihydroxy-3- (4-hydroxyphenyl) propiophenone, belongs to dihydrochalcone compounds, is easily soluble in methanol, ethanol and propanol, is almost insoluble in water, and is soluble in an alkali solution. Phloretin is widely existed in juices of fruits such as apple, pear and various vegetables, is named because the content of covering type or root bark in the plants is concentrated, is a natural active substance, is an antimutagenic factor in food, can be used for treating skin cancer and other tumors, and is a potential chemotherapeutic drug.

Sy, Jye, LEU and the like separate 7 phenolic substances from apples, wherein the phenolic substances comprise phloretin, and the authors test the activity of each substance. According to related research reports, the skin sagging, wrinkle and aging are closely related to the activity enhancement of elastase, and phloretin just can inhibit the activity of elastase. The results of this experiment thus suggest that phloretin may have efficacy in delaying skin aging.

Phloretin has anti-tumor activity, and can be used for treating skin cancer; can prevent glucose from entering sebaceous cells of epidermis, for example, the sebum secretion can be reduced by 90% by wiping the sebaceous cells with 1-2% of phloretin alcohol solution (the volume ratio of propylene glycol to ethanol to polyethylene glycol 200 is 55: 10: 25) for several minutes, and the preparation is suitable for treating acne caused by hypersecretion of sebaceous glands; phloretin has effect in inhibiting phosphorylase and dehydrogenase system of human body, and can inhibit melanin formation, and reduce color of tea brown, gray blemish and freckle when used in facial product; it also has significant oxidation resistance.

The current relatively practical or high-yield synthetic route of phloretin comprises the following steps:

1. the Vidavalur, Siddaiaah Et al synthesized phloretin with phloroglucinol and p-hydroxyphenylpropionic acid in a 30% yield in the presence of BF 3. Et2O as a catalyst. The method has the advantages of simple and cheap raw materials, but has the problems of more side reactions, hydroxyl group protection and low yield.

2. Giardia and the like take phloroglucinol and anisaldehyde as initial raw materials, and the phloretin is prepared by acylation reaction, condensation reaction, esterification reaction, hydrogenation reduction reaction and Fries rearrangement reaction. The process route is long, the toxicity of the used raw materials is too strong, the application of the subsequent phloretin in clinic and cosmetics is not facilitated, the reaction route is hydrogenated, the equipment investment is high, and the danger is high.

3. The method comprises the following steps of taking naringin as a raw material, carrying out catalytic hydrogenation under the condition of alkali liquor and in the presence of a rare metal catalyst to obtain naringin dihydrochalcone, heating and hydrolyzing the naringin dihydrochalcone under the action of dilute acid, and purifying to obtain phloretin. The method requires pressurization or heating in the process of preparing naringin dihydrochalcone, and is not beneficial to operation; when the naringin dihydrochalcone is heated and hydrolyzed under the action of dilute acid, the operation is more, the consumed time is longer, a large amount of waste acid exists, and a large amount of alkali is consumed for neutralization, so that a large amount of saline water is generated, and the cost of subsequent environment-friendly treatment is increased.

Disclosure of Invention

The invention provides a method for synthesizing phloretin from naringenin, aiming at solving the problems of complex synthesis process route, low yield, more side reactions and high cost in the existing phloretin synthesis process.

The technical scheme adopted by the invention is as follows: the method for synthesizing phloretin from naringenin is characterized by comprising the following steps of:

step 1) dissolving a raw material naringenin in a sodium hydroxide ethanol solution with the mass concentration of 4-6%, adding a ternary nickel catalyst, uniformly stirring, heating to 40-45 ℃, carrying out hydrogenation reaction under the hydrogen pressure of 0.8Mpa, and stopping the reaction when the content of the raw material naringenin in a reaction solution is less than 0.65-1% by liquid phase monitoring reaction to obtain an ethanol solution containing the naringenin;

step 2) removing the catalyst in the alcohol solution containing the phloretin, and adjusting the pH value of the alcohol solution containing the phloretin to 5-6;

and 3) concentrating and recovering the reaction liquid treated in the step 2), adding purified water to cool the ethanol until no ethanol exists, filtering and drying to obtain phloretin.

Further, in the step 1), the mass ratio of the naringenin to the sodium hydroxide ethanol solution is 1: 10.

Further, in the step 1), the addition amount of the ternary nickel catalyst is 7% of the mass of the raw material naringenin.

Further, in the step 1), the hydrogenation reaction is carried out for 3-3.5 h.

Further, in the step 3), the mass ratio of the purified water to the raw material naringenin is 1: 2.

Further, in the step 2), the solvent for adjusting the pH value of the ethanol solution containing phloretin is hydrochloric acid.

Further, the specific steps of step 1) are: dissolving 300g of raw material naringenin in 3000g of 6% sodium hydroxide ethanol solution, uniformly stirring, heating to 45 ℃, carrying out hydrogenation reaction for 3.5h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the liquid phase controlled reaction solution is less than 0.88% to obtain the ethanol solution containing the naringenin.

Further, the specific steps of step 3) are: concentrating and recovering the reaction liquid treated in the step 2), adding 600g of purified water to cool to room temperature after ethanol is removed, carrying out suction filtration and drying to obtain phloretin.

Compared with the prior art, the invention has the following beneficial effects.

The method for synthesizing phloretin from naringenin is adopted, the naringenin is subjected to ring opening and dissolution in alkaline ethanol and then is subjected to catalytic hydrogenation by ternary nickel to obtain the phloretin, the phloretin synthesis process is simple, no sewage is generated, no environment-friendly treatment cost is realized, the production cost is reduced, the process yield is high and can reach 92-94%, the method is suitable for large-scale industrial production, and the application range is wider.

Drawings

FIG. 1 is a liquid control phase diagram in example 5 of the present invention.

FIG. 2 is a liquid phase spectrum of the phloretin product of example 5 of the present invention.

Detailed Description

The naringenin is used as a raw material, and the conversion from the naringenin to the phloretin is completed by catalytic hydrogenation in an alkaline ethanol solvent.

The synthesis mechanism of the invention is as follows:

the invention will now be described more fully hereinafter with reference to the accompanying specific embodiments:

example 1

In this embodiment, a method for synthesizing phloretin from naringenin includes the following steps:

dissolving 100g of raw material naringenin in 1000g of sodium hydroxide ethanol solution with the mass concentration of 4%, adding 7g of ternary nickel catalyst, uniformly stirring, heating to 40 ℃, carrying out hydrogenation reaction for 3h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in liquid phase controlled reaction liquid is less than 0.8%, so as to obtain an ethanol solution containing the naringenin;

removing the catalyst from the phloretin-containing ethanol solution, adding hydrochloric acid to adjust the pH value of the reaction solution to 5-6, concentrating and recovering ethanol until no ethanol exists, adding 200g of purified water to cool the solution to room temperature, performing suction filtration and drying to obtain 92 g of 98% phloretin, wherein the liquid phase content of the phloretin is 98.89%, and the yield of refined phloretin is 92%.

Example 2

Dissolving 50g of raw material naringenin in 500g of sodium hydroxide ethanol solution with the mass concentration of 4.5%, adding 3.5g of ternary nickel catalyst, uniformly stirring, heating to 42 ℃, carrying out hydrogenation reaction for 3 hours under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the liquid phase controlled reaction liquid is less than 1% to obtain an ethanol solution containing the phloretin;

removing the catalyst from the phloretin-containing ethanol solution, adding hydrochloric acid to adjust the pH value of the reaction solution to 5-6, concentrating and recovering ethanol until no ethanol exists, adding 100g of purified water to cool the mixture to room temperature, performing suction filtration and drying to obtain 46 g of 98% phloretin, wherein the liquid phase content of the phloretin is 99%, and the yield of refined phloretin is 92%.

Example 3

Dissolving 20g of raw material naringenin in 200g of 5% sodium hydroxide ethanol solution, adding 1.4g of ternary nickel catalyst, uniformly stirring, heating to 40 ℃, carrying out hydrogenation reaction for 3h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the liquid phase controlled reaction liquid is less than 0.65% to obtain an ethanol solution containing the phloretin;

removing the catalyst from the phloretin-containing ethanol solution, adding hydrochloric acid to adjust the pH value of the reaction solution to 5-6, concentrating and recovering ethanol until no ethanol exists, adding 40g of purified water to cool the solution to room temperature, performing suction filtration and drying to obtain 18.3 g of 98% phloretin, wherein the liquid phase content of the phloretin is 98.21%, and the yield of refined phloretin is 91.5%.

Example 4

Dissolving 200g of raw material naringenin in 2000g of 5.5% sodium hydroxide ethanol solution, adding 14g of ternary nickel catalyst, uniformly stirring, heating to 40 ℃, carrying out hydrogenation reaction for 3.2h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the liquid phase control reaction liquid is less than 0.9% to obtain the phloretin-containing ethanol solution;

removing the catalyst from the phloretin-containing ethanol solution, adding hydrochloric acid to adjust the pH value of the reaction solution to 5-6, concentrating and recovering ethanol until no ethanol exists, adding 400g of purified water to cool the solution to room temperature, performing suction filtration and drying to obtain 188 g of 98% phloretin, wherein the liquid phase content of the phloretin is 98.02%, and the yield of refined phloretin is 94%.

Example 5

Dissolving 300g of raw material naringenin in 3000g of 6% sodium hydroxide ethanol solution, adding 21g of ternary nickel catalyst, uniformly stirring, heating to 45 ℃, carrying out hydrogenation reaction for 3.5h under the pressure of 0.8Mp, and stopping the reaction when the content of the raw material naringenin in the reaction liquid in the liquid phase is less than 0.88% as shown in figure 1 to obtain the phloretin-containing ethanol solution;

removing the catalyst from the phloretin-containing ethanol solution, adding hydrochloric acid to adjust the pH value of the reaction solution to 5-6, concentrating and recovering ethanol until no ethanol exists, adding 600g of purified water to cool the solution to room temperature, performing suction filtration and drying to obtain 280 g of 98% phloretin, wherein the liquid phase content of the phloretin is 99.88%, and the yield of refined phloretin is 93.3% as shown in figure 2.

The above description is only an embodiment of the present invention, and is not intended to limit the scope of the present invention, and all equivalent structural changes made by using the contents of the present specification and the drawings, or applied directly or indirectly to other related technical fields, are included in the scope of the present invention.