Preparation method of daidzein

Abstract

A preparation method of daidzein comprises the following steps: S1, mixing hydroxyl-protected 2-chloro-1-(2, 4-dihydroxyphenyl) ethanone, hydroxyl-protected 4-hydroxybenzaldehyde, an alkali reagent and a first solvent in an inert atmosphere, and reacting to obtain an intermediate; s2, dissolving the intermediate in a second solvent in an inert atmosphere to obtain an intermediate solution, adding lewis acid into the intermediate solution, and reacting to obtain daidzein. According to the novel preparation method of daidzein, daidzein is prepared through a two-step method of Darzens condensation reaction and rearrangement reaction, the raw material cost is low, the reaction condition is mild, the yield is high, and emission of three wastes is little; the problem that in the prior art, boron trifluoride is hydrolyzed to generate hydrogen fluoride under the condition of high-temperature reflux during acylation reaction is fundamentally avoided, and the method has huge potential in large-scale production.

Description

Technical Field

[0001] The present invention relates to the field of organic synthetic chemistry, and particularly relates to a method for preparing daidzein. Background Art

[0002] Daidzein, also known as daidzin, with the English name Daidzein, is a natural phytoestrogen. In medicine, food, and health products, it is widely used for the prevention and treatment of breast hyperplasia, osteoporosis, heart disease, menopause syndrome, dementia, and some tumor diseases. At the same time, studies have shown that daidzin can also be used as a feed additive to promote animal growth, reduce feed costs, improve animal fertility, and enhance the body's immunity.

[0003] Daidzein can be extracted from materials such as soy sauce cake, soybeans, soybean meal, and fermented soybean meal used in the production of miso and soy sauce. However, since the content of soy isoflavones in soybeans is only about 2-3%, the soy isoflavones produced by the extraction method cannot meet the needs of the pharmaceutical, food, and feed industries. Therefore, the artificial synthesis of daidzein has become an important production route.

[0004] To date, there have been many reports on the artificial synthesis of daidzein, but the routes with potential for industrial large-scale production are all two-step routes starting from resorcinol and p-hydroxy phenylacetic acid:

[0005]

[0006] In the traditional synthesis route, the first acylation reaction requires the catalysis of Lewis acid. Commonly used Lewis acids include aluminum trichloride, zinc dichloride, boron trifluoride, etc. Among them, boron trifluoride has been widely used due to its better catalytic effect. For example, a method for extracting daidzein disclosed in Patent CN118063423B uses boron trifluoride etherate as a catalyst. However, water is generated during the acylation reaction, and boron trifluoride will hydrolyze to produce trace amounts of highly toxic and highly corrosive hydrogen fluoride under high-temperature reflux conditions, posing safety hazards to operators and reaction equipment during industrial production. In addition, in the second step of the traditional synthesis route, triethyl orthoformate, or N,N-dimethylformamide dimethyl acetal, or Vilsmeier reagent, etc. are required to provide a carbon atom to achieve the carbon-carbon ring closure reaction. The yield of this step is usually not high, and a large amount of three wastes are easily generated, increasing the industrial production cost. Moreover, the starting material p-hydroxy phenylacetic acid is expensive, which also leads to an increase in the overall cost of the production process.

[0007] Therefore, it is necessary to redesign the traditional method for synthesizing daidzein to reduce the industrial production cost and improve production safety. Summary of the Invention

[0008] The object of the present invention is to provide a method for preparing daidzein, which uses chloroacetyl resorcinol and p-hydroxybenzaldehyde as starting materials, and prepares daidzein through two steps of Darzens condensation and rearrangement reactions, solving the problems that hydrogen fluoride is generated in the first acylation reaction and the three wastes are high in the second cyclization reaction in the prior art. The reaction conditions are milder, and the yield can be effectively improved, which is beneficial to the industrial large-scale production of daidzein.

[0009] The present invention is achieved through the following technical solutions:

[0010] A method for preparing daidzein, comprising the following steps:

[0011] S1: Under an inert atmosphere, mix hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, hydroxy-protected 4-hydroxybenzaldehyde, a base reagent, and a first solvent, and react to obtain an intermediate;

[0012] S2: Under an inert atmosphere, dissolve the intermediate in a second solvent to obtain an intermediate solution, and add a Lewis acid to the intermediate solution to react to obtain the daidzein.

[0013] In this technical solution, hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone and hydroxy-protected 4-hydroxybenzaldehyde are used as raw materials, and a Darzens condensation reaction occurs in a basic environment to obtain an intermediate compound shown in Formula IV. Its synthesis route is:

[0014]

[0015] Among them, the R1, R2, and R3 groups are hydroxy-protecting groups, and the three hydroxy-protecting groups can be the same or different. In some preferred embodiments, the R1, R2, and R3 groups are independently selected from methoxymethyl ether, tert-butyl, p-methoxybenzyl, 2-tetrahydropyran, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trityl, or tert-butoxycarbonyl. Further preferably, the R1, R2, and R3 groups are all methoxymethyl ether (MOM).

[0016] In this technical solution, the intermediate dissolved in the second solvent undergoes a rearrangement reaction with a Lewis acid to obtain the final product daidzein. Its synthesis route is:

[0017]

[0018] In this technical solution, intermediate IV is synthesized through the Darzens condensation reaction under alkaline conditions, which can fundamentally avoid the problem that boron trifluoride hydrolyzes to generate hydrogen fluoride during the acylation reaction in the prior art. Moreover, the reaction conditions are milder. For example, in some preferred embodiments, the reaction temperature of the Darzens condensation reaction is 0-30 °C, that is, the reaction can be completed at room temperature, greatly reducing the production cost and improving safety. At the same time, compared with the prior art method using resorcinol and 4-hydroxyphenylacetic acid as starting materials, 2-chloro-1-(2,4-dihydroxyphenyl)ethanone and 4-hydroxybenzaldehyde have lower costs and are easier to obtain, thus further reducing the reaction cost and having great potential in large-scale production.

[0019] In this technical solution, the intermediate solution undergoes a rearrangement reaction with a Lewis acid. Although a Lewis acid is used in this step, water will not be generated during the reaction process as in the acylation reaction in the first step of the prior art. Therefore, boron trifluoride is stable during the entire rearrangement reaction process and is not likely to generate highly corrosive substances such as hydrogen fluoride. Moreover, the requirements for the reaction temperature and reaction time of the rearrangement reaction are lower than those of the acylation reaction, effectively ensuring the safety of the two-step reaction. Not only that, the yields of the two-step reactions of the Darzens condensation and rearrangement reactions are relatively high, which can effectively reduce the emission of three wastes and lower the cost of post-treatment of the production process.

[0020] In one or more embodiments, the inert atmosphere is nitrogen or argon protection.

[0021] Further, the molar ratio of the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to the hydroxy-protected 4-hydroxybenzaldehyde is 1:1 to 1:1.5.

[0022] In this technical solution, an equimolar reaction of the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone and the hydroxy-protected 4-hydroxybenzaldehyde is sufficient. Preferably, in order to ensure the complete reaction of 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, 4-hydroxybenzaldehyde is added in excess. Therefore, in this technical solution, the molar ratio of the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to 4-hydroxybenzaldehyde is further limited to 1:1 to 1:1.5. In a more preferred embodiment, the molar ratio of the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to the hydroxy-protected 4-hydroxybenzaldehyde is 1:1 to 1:1.2.

[0023] Further, the base reagent used in the Darzens condensation reaction in the present invention can be an organic base, such as at least one of triethylamine, diethylamine, N,N - diisopropylethylamine, 1,8 - diazabicyclo[5.4.0]undec - 7 - ene, potassium tert - butoxide, sodium tert - butoxide, sodium methoxide, and sodium ethoxide; or it can be an inorganic base, such as at least one of sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

[0024] In some preferred embodiments, the organic base is triethylamine or 1,8 - diazabicyclo[5.4.0]undec - 7 - ene (DBU); the inorganic base is sodium hydroxide or potassium hydroxide.

[0025] Further, the first solvent used in the Darzens condensation reaction in the present invention can be an alcohol solvent, such as at least one of methanol, ethanol, n - propanol, isopropanol, n - butanol, and isobutanol; it can be an aromatic solvent, such as at least one of benzene, toluene, xylene, and chlorobenzene; or it can be other solvents, such as at least one of acetonitrile, N,N - dimethylformamide, N,N - dimethylacetamide, dimethyl sulfoxide, acetone, and N - methylpyrrolidone.

[0026] In some preferred embodiments, the first solvent is methanol, ethanol or N,N - dimethylformamide.

[0027] Further, in step S1, after the hydroxy - protected 2 - chloro - 1-(2,4 - dihydroxyphenyl)ethanone, hydroxy - protected 4 - hydroxybenzaldehyde, base reagent, and first solvent are mixed evenly, they react at 0 - 60 °C to obtain the intermediate.

[0028] In this technical solution, the reaction temperature of the Darzens condensation reaction is significantly lower than that of the acylation reaction in the prior art, thus significantly reducing production costs and improving safety. In one or more embodiments, the reaction temperature of the Darzens condensation reaction is 0 - 60 °C. Preferably, the reaction temperature is 0 - 30 °C. More preferably, the Darzens condensation reaction is carried out at room temperature.

[0029] Further, the Lewis acid is at least one of boron trifluoride, chlorine trichloride, tin tetrachloride, and zinc dichloride. Preferably, the Lewis acid is boron trifluoride.

[0030] Further, the second solvent used in the rearrangement reaction in the present invention may be an ether solvent, such as at least one of diethyl ether, tetrahydrofuran, and methyl tert-butyl ether; it may be an aromatic solvent, such as at least one of dioxane, benzene, toluene, xylene, and chlorobenzene; it may also be other solvents, such as acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetone, butanone, and N-methylpyrrolidone.

[0031] In the second rearrangement reaction, the second solvent does not introduce water into the reaction system. At the same time, by selecting a reasonable second solvent, the heating reflux temperature during the rearrangement reaction can be lower, effectively reducing the production cost. In some preferred embodiments, the second solvent is diethyl ether or tetrahydrofuran.

[0032] Further, in step S2, the intermediate solution and the Lewis acid react at 0 to 150 °C to obtain the daidzein. Preferably, the reaction temperature of the intermediate solution and the Lewis acid is 0 to 120 °C.

[0033] The present invention also provides a method for preparing daidzein. Specifically, it includes the following steps:

[0034] Hydroxy-protect the two hydroxyl groups of 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to obtain hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone;

[0035] Hydroxy-protect the hydroxyl group of 4-hydroxybenzaldehyde to obtain hydroxy-protected 4-hydroxybenzaldehyde;

[0036] Under an inert atmosphere, the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, hydroxy-protected 4-hydroxybenzaldehyde, and the base reagent are dissolved in the first solvent to obtain a first mixture, and the first mixture reacts at 0 to 60 °C to obtain an intermediate;

[0037] The intermediate is heated and refluxed with a Lewis acid under an inert atmosphere to obtain the daidzein.

[0038] In some preferred embodiments, the hydroxy-protecting group may be methoxymethyl ether, tert-butyl, p-methoxybenzyl, 2-tetrahydropyranyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trityl, or tert-butoxycarbonyl.

[0039] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0040] 1. The intermediate IV is synthesized by the Darzens condensation reaction under alkaline conditions in the present invention, which can avoid the problem that boron trifluoride hydrolyzes to generate hydrogen fluoride under high-temperature reflux conditions during the acylation reaction in the prior art from the root cause. The overall reaction is milder, significantly reducing the production cost and improving the safety, and having great potential in large-scale production;

[0041] 2. The present invention prepares daidzein by a two-step method of Darzens condensation reaction and rearrangement reaction, which can obtain a high yield, effectively reduce the emission of three wastes, and reduce the cost of post-treatment of the production process;

[0042] 3. The costs of the starting materials 2-chloro-1-(2,4-dihydroxyphenyl)ethanone and 4-hydroxybenzaldehyde in the present invention are lower than those of traditional resorcinol and p-hydroxyphenylacetic acid, so the reaction cost can be further reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The drawings described herein are used to provide a further understanding of the embodiments of the present invention, form a part of the present invention, and do not constitute a limitation on the embodiments of the present invention. In the drawings:

[0044] Figure 1 is a flowchart of the preparation method in the specific embodiment of the present invention;

[0045] Figure 2 is the 1 H NMR spectrum of compound IV in which the protecting groups R1, R2, and R3 are all MOM in the specific embodiment of the present invention;

[0046] Figure 3 is the 1 H NMR spectrum of daidzein in the specific embodiment of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0047] To make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in combination with embodiments and drawings. The illustrative embodiments and descriptions thereof of the present invention are only used to explain the present invention and do not constitute a limitation on the present invention.

[0048] For all raw materials of the present invention, there is no particular limitation on their sources, and they can be purchased on the market or prepared according to the conventional methods well-known to those skilled in the art. For all raw materials of the present invention, there is no particular limitation on their purity. The present invention preferably uses analytical pure or the conventional purity requirements in the field of organic synthetic chemistry. For all raw materials of the present invention, their trade names and abbreviations are all conventional trade names and abbreviations in the field, and each trade name and abbreviation is clear and definite in the field of its relevant uses. Those skilled in the art can purchase them from the market or prepare them by conventional methods according to the trade name, abbreviation, and corresponding uses.

[0049] The present invention has no particular limitation on the expression of the substituents, and the expressions well-known to those skilled in the art are adopted. Based on common knowledge, those skilled in the art can correctly understand their meanings according to their expressions.

[0050] In the present invention, "first", "second", etc. (such as the first solvent, the second solvent, etc.) used are only for distinguishing the corresponding components for the sake of clear description, and are not intended to limit any order or emphasize importance, etc. In addition, the term "connection" used in the present invention, without special explanation, can be directly connected or indirectly connected via other groups.

[0051] In the present invention, daidzein is prepared using 2-chloro-1-(2,4-dihydroxyphenyl)ethanone as the starting material. In some preferred embodiments, daidzein is prepared using the hydroxyl-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone shown in Formula II and the hydroxyl-protected 4-hydroxybenzaldehyde shown in Formula III. The synthetic route of daidzein is as follows:

[0052]

[0053] Among them, the groups R1, R2, and R3 are protecting groups. In some preferred embodiments, R1, R2, and R3 can independently be selected from methoxymethyl ether (-MOM), tert-butyl (t-Bu), p-methoxybenzyl (PMB), 2-tetrahydropyranyl (THP), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), trityl (Tr), or tert-butoxycarbonyl (Boc).

[0054]

Example 1

[0055] (1) Preparation of Compound IV

[0056] In a dry reaction flask under nitrogen protection, compound II (20.0 g, 73 mmol, R1 = -MOM, R2 = -MOM), 200 mL of absolute ethanol, compound III (14.4 g, 87 mmol, R3 = -MOM), and 5% aqueous sodium hydroxide solution (230 mL) were successively added. The mixture was stirred at room temperature for 12 h. After monitoring the completion of the reaction by TLC, the reaction solution was cooled to 0 °C and neutralized to neutral with dilute hydrochloric acid. It was extracted with 3 × 150 mL of isopropyl acetate, the organic phase was washed with 3 × 150 mL of saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was crystallized with ethyl acetate / n-heptane to obtain 23.9 g of compound IV (R1 = -MOM, R2 = -MOM, R3 = -MOM) with a yield of 81%.

[0057] Perform 11H NMR identification was carried out using a Bruker Avance-400 NMR spectrometer. CDCl3 was used as the solvent and TMS as the internal standard. The obtained 1 1H NMR spectrum is as Figure 2 shown, specifically:

[0058] 1 1H NMR(CDCl3,400MHz)δ7.84(d,J=8.6Hz,1H),7.32~7.26(m,2H),7.08~7.01(m,2H),6.80~6.72(m,2H),5.22~5.17(m,4H),4.92(d,J=6.9Hz,1H),4.84(d,J=6.9Hz,1H),4.30(d,J=1.9Hz,1H),3.93(d,J=2.0Hz,1H),3.47(d,J=3.9Hz,6H),3.13(s,3H).

[0059] (2) Preparation of daidzein I

[0060] At room temperature, compound IV (10.0 g, 25.0 mmol) and 50 mL of anhydrous ether were successively added to a dry reaction flask under nitrogen protection, stirred and dissolved. Then 3.0 mL of boron trifluoride etherate was added. The obtained reaction solution was heated to reflux. After monitoring by TLC that the raw materials had completely reacted, the reaction solution was cooled to room temperature, diluted with 100 mL of isopropyl acetate. The obtained solution was washed three times with water and once with saturated NaCl aqueous solution. The organic phase was dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was recrystallized with 95% ethanol to obtain 4.7 g of daidzein, with a yield of 75%.

[0061] The prepared daidzein I was subjected to 1 1H NMR identification, which was measured using a Bruker Avance-400 NMR spectrometer with MeOH-d4 as the solvent and TMS as the internal standard. The obtained 1 1H NMR spectrum is as Figure 3 shown, specifically:

[0062] 1 1H NMR(MeOH-d4,400MHz)δ8.15(s,1H),8.08(d,J=8.9Hz,1H),7.39(d,J=8.7Hz,2H),6.96(dd,J=8.8,2.3Hz,1H),6.84~6.89(m,3H).

[0063]

Example 2

[0064] In this example, different from Example 1, compound IV was prepared in the following manner.

[0065] In a dry reaction flask under nitrogen protection, compound II (20.0 g, 73 mmol, R1 = -MOM, R2 = -MOM), 200 mL of tetrahydrofuran, compound III (13.2 g, 80.3 mmol, R3 = -MOM) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (16.6 g, 109.5 mmol) were successively added. The mixture was stirred at room temperature for 12 h. After monitoring the completion of the reaction by TLC, the reaction solution was concentrated under reduced pressure. The residue was added with 3 × 150 mL of isopropyl acetate, washed successively with 3 × 100 mL of dilute hydrochloric acid and 3 × 100 mL of saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was crystallized with ethyl acetate / n-heptane to obtain 25.0 g of compound IV (R1 = -MOM, R2 = -MOM, R3 = -MOM) with a yield of 85%. Its 1 1H NMR spectrum was consistent with that of compound IV in Example 1.

[0066]

Example 3

[0067] In this example, different from Example 1, daidzein I was prepared in the following manner.

[0068] At room temperature, compound IV (20.0 g, 50.0 mmol) and 100 mL of methyl tert-butyl ether were successively added to a dry reaction flask under nitrogen protection, stirred and dissolved, and then 6.0 mL of boron trifluoride diethyl ether was added. The obtained reaction solution was heated to reflux. After monitoring the complete reaction of the raw materials by TLC, the reaction solution was cooled to room temperature, diluted with 200 mL of isopropyl acetate, and the obtained solution was washed three times with water and once with saturated NaCl aqueous solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product, which was recrystallized with 95% ethanol to obtain 10.8 g of daidzein with a yield of 85%. Its 1 1H NMR spectrum was consistent with that of daidzein in Example 1.

[0069]

Example 4

[0070] In this example, a method for protecting the hydroxyl groups in 2-chloro-1-(2,4-dihydroxyphenyl)ethanone with MOM was disclosed.

[0071] Specifically, add 2-chloro-1-(2,4-dihydroxyphenyl)ethanone (26 g) and dichloromethane (250 mL) into a dry reaction flask, stir to dissolve, and then add N,N-diisopropylethylamine (98 mL). Cool the resulting solution to 0 °C, and then slowly add chloromethyl methyl ether (44 mL) dropwise. After the dropwise addition is completed, stir at 25 °C for 18 hours. Quench the reaction with cold water and dilute with ethyl acetate (500 mL). Wash the solution with saturated brine. After phase separation, dry the organic phase with anhydrous sodium sulfate and concentrate under reduced pressure to obtain 34.5 g of compound II (R1=-MOM, R2=-MOM) with a yield of 90%.

[0072] 1 H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.8 Hz, 1H), 6.84 (d, J = 2.3 Hz, 1H), 6.75 (dd, J = 8.8, 2.2 Hz, 1H), 5.29 (s, 2H), 5.20 (s, 2H), 4.76 (s, 2H), 3.53 (s, 3H), 3.47 (s, 3H).

[0073] Those skilled in the art should understand that although only the protection of two hydroxyl groups of 2-chloro-1-(2,4-dihydroxyphenyl)ethanone with MOM is disclosed in this embodiment, other known protecting groups can also be used for the protection of hydroxyl groups. In one or more embodiments, the protecting group can also be tert-butyl (t-Bu), p-methoxybenzyl (PMB), 2-tetrahydropyranyl (THP), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), trityl (Tr), or tert-butoxycarbonyl (Boc).

[0074]

Example 5

[0075] A method for protecting the hydroxyl group in 4-hydroxybenzaldehyde with MOM is disclosed in this embodiment.

[0076] Specifically, add 4-hydroxybenzaldehyde (20 g) and dichloromethane (200 mL) into a dry reaction flask, stir to dissolve, and then add N,N-diisopropylethylamine (85 mL). Cool the solution to 0 °C, and then slowly add chloromethyl methyl ether (20 g) dropwise. After the dropwise addition is completed, stir the mixture at 25 °C for 18 hours. Quench the reaction solution with cold water and dilute with ethyl acetate (300 mL), and wash the resulting solution with saturated brine. After phase separation, dry the organic phase with anhydrous sodium sulfate and concentrate under reduced pressure to obtain 24.5 g of compound III (R3=-MOM) with a yield of 90%.

[0077] 11H NMR (400 MHz, Chloroform-d) δ 9.90 (s, 1H), 7.88–7.79 (m, 2H), 7.19–7.10 (m, 2H), 5.25 (s, 2H), 3.49 (s, 3H).

[0078] Those skilled in the art should understand that although only the protection of the hydroxyl group of 4-hydroxybenzaldehyde with MOM is disclosed in this embodiment, other known protecting groups can also be used for the protection of the hydroxyl group. In one or more embodiments, the protecting group can also be tert-butyl (t-Bu), p-methoxybenzyl (PMB), 2-tetrahydropyranyl (THP), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), trityl (Tr) or tert-butoxycarbonyl (Boc).

[0079] The specific embodiments described above have further elaborated on the purpose, technical solution and beneficial effects of the present invention. It should be understood that the above description is only the specific embodiments of the present invention and is not used to limit the protection scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing daidzein, characterized in that: The following steps are involved: S1: Under an inert atmosphere, mixing hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, hydroxy-protected 4-hydroxybenzaldehyde, a base reagent, and a first solvent to react to obtain an intermediate; S2: Under an inert atmosphere, the intermediate is dissolved in a second solvent to obtain an intermediate solution, and Lewis acid is added to the intermediate solution to react to obtain the daidzein.

2. The method for preparing daidzein according to claim 1, wherein The molar ratio of the hydroxyl-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to the hydroxyl-protected 4-hydroxybenzaldehyde is 1:1 to 1:1.

5.

3. The method for preparing daidzein according to claim 1, wherein The alkaline reagent is at least one of triethylamine, diethylamine, N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium tert-butoxide, sodium tert-butoxide, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

4. The method for preparing daidzein according to claim 1, wherein The first solvent is at least one of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, benzene, toluene, xylene, chlorobenzene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetone, and N-methylpyrrolidone.

5. The method for preparing daidzein according to claim 1, wherein In step S1, hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, hydroxy-protected 4-hydroxybenzaldehyde, an alkaline reagent, and a first solvent are uniformly mixed and reacted at 0-60° C. to obtain the intermediate.

6. The method for preparing daidzein according to claim 1, wherein The Lewis acid is at least one of boron trifluoride, chlorine trichloride, tin tetrachloride and zinc dichloride.

7. The method for preparing daidzein according to claim 1, wherein The second solvent is diethyl ether, tetrahydrofuran, methyl tert-butyl ether, dioxane, benzene, toluene, xylene, chlorobenzene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetone, butanone, or N-methylpyrrolidone.

8. The method for preparing daidzein according to claim 1, wherein In step S2, the intermediate solution reacts with the Lewis acid at 0-150° C. to prepare the daidzein.

9. A method for preparing daidzein according to any one of claims 1 to 8, characterized in that: The first protecting group and the second protecting group for protecting the two hydroxyl groups of the hydroxy-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone are independently selected from methoxymethyl ether, tert-butyl, p-methoxybenzyl, 2-tetrahydropyran, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trityl or tert-butyloxycarbonyl; the third protecting group for protecting the hydroxyl group of the hydroxy-protected 4-hydroxybenzaldehyde is selected from methoxymethyl ether, tert-butyl, p-methoxybenzyl, 2-tetrahydropyran, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trityl or tert-butyloxycarbonyl.

10. A method for preparing daidzein, characterized in that: The following steps are involved: Protecting the two hydroxyl groups of 2-chloro-1-(2,4-dihydroxyphenyl)ethanone to obtain hydroxyl-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone; Protecting the hydroxyl group of 4-hydroxybenzaldehyde to obtain hydroxyl-protected 4-hydroxybenzaldehyde; Under an inert atmosphere, the hydroxyl-protected 2-chloro-1-(2,4-dihydroxyphenyl)ethanone, the hydroxyl-protected 4-hydroxybenzaldehyde, and the alkaline reagent are dissolved in a first solvent to obtain a first mixture, and the first mixture is reacted at 0 to 60° C. to obtain an intermediate; The intermediate is reacted with Lewis acid under heating reflux in an inert atmosphere to prepare the daidzein.

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