4, 4, 4apos; synthesis method of-(2-pyridylmethyl) bisphenol

Abstract

The invention provides a synthesis method of 4, 4 '-(2-pyridylmethyl) bisphenol, which comprises the following steps: (1) 2-pyridine formyl chloride hydrochloride and phenyl ether are subjected to Friedel-Crafts acylation to obtain a compound II; (2) obtaining a compound III from the compound II under the action of a reducing agent sodium borohydride or potassium borohydride; (3) performing Friedel-Crafts alkylation on the compound III and phenol to obtain a compound IV; and (4) carrying out dealkylation on the compound IV in a reducing agent hydrobromic acid or hydroiodic acid to obtain the compound I 4, 4 '(2-pyridylmethyl) bisphenol. The method has the advantages of high yield, mild reaction conditions, few byproducts and simple process, and has high industrial application value.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of drug synthesis, and particularly relates to a synthesis method of 4,4'-(2-pyridylmethyl) bisphenol. BACKGROUND

[0002] Bisacodyl and sodium picosulfate are widely used in clinic as highly effective stimulant laxatives, playing a vital role in the treatment of constipation and intestinal cleansing preparation before medical procedures such as colonoscopy. Bisacodyl directly stimulates the intestinal wall nerves through its active metabolite produced by hydrolysis in the intestinal tract, enhancing colonic peristalsis and promoting secretion. Sodium picosulfate is a unique prodrug, which is inactive by itself and needs to be metabolized by colonic flora into the active form diphenol to exert the effect of promoting defecation. Due to its exact efficacy and relatively good tolerability (when used for a short period according to the instructions), these two drugs have a sustained and huge market demand worldwide.

[0003] Bisacodyl and sodium picosulfate differ in chemical structure, but both share a key intermediate, 4,4'-(2-pyridylmethyl) bisphenol (Compound I). The preparation methods of 4,4'-(2-pyridylmethyl) bisphenol reported in the literature mainly include the following: Method one (Zhang Junhui; Liu Yinghua; Li Jinling; et al. Synthesis of Bisacodyl [J]. Fine Chemical Intermediates, 2012, 42(02), 30-32.): Zhang Junhui et al. improved the synthesis route using 2-pyridine formaldehyde and phenol as starting materials. 2-Pyridine formaldehyde and phenol were subjected to Friedel-Crafts alkylation to obtain the product 4,4'-dihydroxydiphenyl-(2-pyridyl)methane, and the ortho isomer 2,4'-dihydroxydiphenyl-(2-pyridyl)methane. The main product (Compound I) was obtained by recrystallization with ethanol. This route has the advantage of short route. However, the starting material 2-pyridine formaldehyde is relatively expensive and is prone to oxidation, making it difficult to store; the Friedel-Crafts alkylation step generates a large amount of ortho isomer impurities, resulting in large waste of raw materials and more "three wastes"; the reaction of phenol and 2-pyridine formaldehyde in the absence of solvent is a heterogeneous reaction, which is difficult to stir at low temperature, and the reaction liquid is very viscous, which requires high requirements for production equipment.

[0004] ; Method two: when preparing the key intermediate (compound I) and then synthesizing pyridine sodium sulfate, 2-pyridine carboxaldehyde and anisole are used as starting materials, 2-pyridine carboxaldehyde and anisole are subjected to Friedel-Crafts alkylation reaction under the catalysis of concentrated sulfuric acid to synthesize 4,4'-dimethoxydiphenyl-(2-pyridyl)-methane, and then demethylation is carried out under the catalysis of DL-methionine and methanesulfonic acid to synthesize 4,4'-dihydroxydiphenyl-(2-pyridyl) methane (compound I). The starting material 2-pyridine carboxaldehyde is relatively expensive, and the demethylation condition is relatively harsh.

[0005] ; Method three: patent CN 113943247 A uses 4,4'-dimethoxybenzophenone as a starting material, reduces it by sodium borohydride to obtain 4,4'-dimethoxybenzyl alcohol, chlorosulfuric acid is used for chlorination to obtain 4,4'-(chloromethylene) bis(methoxybenzene), and then Friedel-Crafts alkylation reaction is carried out with pyridine to obtain 4,4'-dimethoxydiphenyl-(2-pyridyl)-methane, and demethylation is carried out under the condition of aluminum chloride to generate the key intermediate 4,4'-dihydroxydiphenyl-(2-pyridyl) methane (compound I). The reaction temperature is relatively mild, and the synthesis steps are relatively long. The starting material is expensive; chloroform is used as a solvent, which has high volatility and potential carcinogenicity.

[0006] ; Method four (Zhang, Z. Y.; Yadagiri, D.; Gevorgyan, V. Light-induced metal-free transformations of unactivated pyridotriazoles[J]. Chem. Sci .2019, 10(36) ,8399-8404.): Zhang Ziyuan et al. carry out arylization reaction with 3-(4-methoxyphenyl)[1,2,3]triazolo[1,5-a]pyridine and 4-(isobutyldimethylsilyloxy)benzene boronic acid to obtain 2-[4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl](4-methoxyphenyl)methyl]pyridine, and then demethylation and silicon-oxygen bond cleavage are carried out to obtain compound I. The synthesis route is relatively short, the total yield is 74%, and the yield is relatively high; the starting material is rare and expensive; benzene is used as a solvent in the first step reaction, and benzene is a carcinogen; it does not have industrialization potential.

[0007] ; Method five (Mereyala, HB; Sambaru, K. Synthesis of triphenylmethanederivative. Bisacodyl[J]. Indian J. Chem 2005, 44B(3) (615-617.): Mereyala et al., using 2-pyridinecarboxylic acid as the starting material and benzene as the solvent, prepared 2-pyridinecarboxyl chloride hydrochloride under reflux of thionyl chloride. Then, it reacted with phenol under triethylamine catalysis to obtain phenol 2-pyridinecarboxylic acid ester. The ester underwent Fries rearrangement at 160°C under aluminum chloride catalysis to give 4-hydroxyphenyl-(2-pyridyl)-one and 2-hydroxyphenyl-(2-pyridyl)-one in a ratio of 2:1. Pure 4-hydroxyphenyl-(2-pyridyl)-one was obtained by column chromatography. It was then reduced with potassium borohydride to obtain 4-hydroxyphenyl-(2-pyridyl)-methanol, which was then condensed with phenol under concentrated sulfuric acid catalysis to give compound I. 2-Pyridinecarboxylic acid is cheaper and more readily available than 2-pyridinecarboxaldehyde; the synthetic route is relatively long and the overall yield is only 12.0%; the first step of the reaction uses benzene as a solvent, and benzene is a Class I carcinogen; the ortho-para selectivity after Fries rearrangement is poor, stirring is extremely difficult, and there are many impurities, making this method unsuitable for industrial production.

[0008] ; Method Six (Xia Zekuan; Zuo Jinfu. Improved Synthesis Process of Bisacodyl [J]). Shandong Pharm. Ind. 2002, (03) 1.): Xia Zekuan et al. used 2-pyridinemethanol as a raw material and synthesized 2-pyridinecarboxaldehyde by oxidation with lead tetraacetate, followed by addition with sulfur dioxide to obtain 2-pyridine-hydroxymethanesulfonic acid, which was then subjected to Friedel-Crafts alkylation with phenol to obtain compound I. Advantages: High reaction yield; lead tetraacetate can be recycled, reducing the cost of this raw material. Disadvantages: The synthesis process uses organic solvents such as chloroform and benzene, which are volatile and carcinogenic; lead tetraacetate is a heavy metal compound with high toxicity and significant environmental pollution; the raw material 2-pyridinemethanol is expensive; sulfur dioxide has a pungent odor and high toxicity, causing significant environmental impact.

[0009] ; Method 7: Patent CN105175317A

[42] uses 2-pyridinecarboxaldehyde and 2-chlorophenol as starting materials, and carries out a condensation reaction under concentrated sulfuric acid catalysis to generate 3,3'-dichloro-4,4'-(pyridine-2-ylmethylene)bisphenol, which is then reduced by nickel-aluminum alloy to obtain compound I. The synthetic route is relatively short; the starting material 2-pyridinecarboxaldehyde is relatively expensive, easily oxidized and difficult to store; when nickel-aluminum alloy is reduced and dechlorinated, a large amount of hydrogen gas is released, which is not conducive to safe production.

[0010] ; Therefore, it is necessary to invent a method for preparing 4,4'-(2-pyridinemethyl)bisphenol that uses inexpensive and readily available raw materials, has a simple process, and produces a high-purity product. Summary of the Invention

[0011] The main objective of this invention is to address the above-mentioned problems by providing a method for synthesizing 4,4'-(2-pyridinemethyl)bisphenol, which uses inexpensive and readily available raw materials, has a simple process, and produces a high-purity product.

[0012] To achieve the above objectives, the present invention provides a method for synthesizing 4,4'-(2-pyridinemethyl)bisphenol, characterized in that the method comprises the following steps: (1) 2-pyridinecarboxyl chloride hydrochloride was subjected to Friedel-Crafts acylation with phenyl ether to give compound II; (2) Compound II is reacted with reducing agents such as sodium borohydride or potassium borohydride to obtain compound III; (3) Compound III was subjected to Friedel-Crafts alkylation with phenol to obtain compound IV; (4) Compound IV is dealkylated in the reducing agent hydrobromic acid or hydroiodic acid to give compound I 4,4'(2-pyridinemethyl)bisphenol; .

[0013] Preferably, the solvent used in step (1) is selected from one or more of dichloromethane, chloroform, chlorobenzene, nitrobenzene, dichloroethane, or trichloroethane; preferably dichloroethane; the catalyst used is one or more of anhydrous aluminum trichloride, ferric chloride, zinc chloride, titanium tetrachloride, boron trichloride, or boron trifluoride; preferably aluminum trichloride; the reaction temperature is 40–85°C; and the reaction time is 1–10 h.

[0014] Preferably, the molar ratio of 2-pyridinecarboxyl chloride hydrochloride, phenyl ether, and catalyst is 1:1.1-1.5:1.5-2.5.

[0015] Preferably, the solvent used in step (2) is selected from methanol, ethanol, isopropanol and tetrahydrofuran, with methanol being the most preferred; the molar ratio of compound II to reducing agent is 1:0.3-0.5; the reaction temperature is 0-30℃; and the reaction time is 0.5-5 h.

[0016] Preferably, the organic solvent in step (3) is one or more of dichloromethane, chloroform, chlorobenzene, nitrobenzene, dichloroethane, or trichloroethane; preferably nitrobenzene; the catalyst is one or more of concentrated sulfuric acid, hydrochloric acid, anhydrous aluminum trichloride, ferric chloride, zinc chloride, titanium tetrachloride, boron trichloride, or boron trifluoride; preferably concentrated sulfuric acid; the molar ratio of compound III, phenol, and catalyst is 1:1.0-1.3:2.0-4.0; the reaction temperature is 0-30℃; and the reaction time is 0.5-2.0 h.

[0017] Preferably, in step (4), the molar ratio of compound IV to reducing agent is 1:2.0-5.0; the reaction temperature is 80-110℃; and the reaction time is 2.0-8.0 h.

[0018] Better place, Step (1) further includes: adding the reaction solution dropwise to ice water to quench it, adjusting the pH value with an alkaline reagent, solvent extraction and concentrating the extract; Step (2) further includes: quenching with water, precipitating solids, and filtration; Step (3) further includes: adding the reaction solution dropwise into ice water, adjusting the pH value with an alkaline reagent to precipitate the solid, and then filtering it; Step (4) further includes: cooling, adjusting the pH value with an alkaline reagent to precipitate the solid, and then filtration.

[0019] Preferably, the method specifically includes the following steps: (1) Add anhydrous aluminum chloride and 2-pyridinecarboxyl chloride hydrochloride to the solvent, raise the temperature to the reaction temperature, add anisole dropwise to react, quench the reaction solution dropwise in ice water, adjust the pH value with an alkaline reagent, extract with solvent and concentrate the extract to obtain compound II. The extraction solvent is dichloromethane or dichloroethane. (2) Add compound II to an organic solvent, and then add sodium borohydride or potassium borohydride as a reducing agent. After the reaction is complete, add water to quench the reaction, precipitate the solid, and filter to obtain compound III. (3) Dissolve compound III and phenol in an organic solvent, add concentrated sulfuric acid dropwise in an ice bath to carry out the reaction, after the reaction is completed, add the reaction solution dropwise to ice water, adjust the pH value with an alkaline reagent to precipitate the solid, and then filter to obtain compound IV; (4) Add reducing agent hydrobromic acid or hydroiodic acid to compound IV to react, cool down, adjust the pH value with alkaline reagent to precipitate solid, and then filter to obtain compound I 4,4' (2-pyridinemethyl)bisphenol.

[0020] The method for synthesizing the key intermediate of telmisartan of the present invention uses pyridine-2-formyl chloride hydrochloride as a raw material, which is selectively Friedel-Crafts acylated with anisole to generate compound II, compound II is reduced to generate compound III, compound III is Friedel-Crafts alkylated with phenol to obtain compound IV, and compound IV is demethylated to obtain compound I, namely 4,4'-(2-pyridinemethyl)bisphenol. The present invention has the advantages of high yield, mild reaction conditions, few by-products and simple process, and has high industrial application value.

[0021] The preparation method of this invention uses inexpensive and readily available raw materials, has a simple process route, and is safe and conventional in operation. It can be achieved using conventional equipment and conditions, and reduces or even avoids impurities caused by reaction selectivity while consistently obtaining superior yields and purity of 4,4'-(2-pyridinemethyl)bisphenol. In addition, this invention eliminates the need for complex purification operations on all intermediates, and the subsequent three reaction steps only require filtration to obtain products with excellent purity. Attached Figure Description

[0022] Figure 1 and Figure 2 The spectrum is that of (4-methoxyphenyl)-2-pyridyl ketone (compound II) in Example 1.

[0023] Figure 3 and Figure 4 The spectrum of α-(4-methoxyphenyl)-2-pyridylmethanol (compound III) in Example 1 is shown.

[0024] Figure 5 and Figure 6 The spectrum of 4-[(4-methoxyphenyl)-2-pyridinemethyl]phenol (compound IV) in Example 1 is shown.

[0025] Figure 7 and Figure 8 The spectrum shows the yield of 4,4' (2-pyridinemethyl)bisphenol (compound I) in Example 1. Detailed Implementation

[0026] To provide a clearer understanding of the technical content of this invention, the following embodiments are provided in detail. However, it is important to note that these descriptions are merely for further illustrating the features and advantages of this invention, and not for limiting the scope of the claims.

[0027] Unless otherwise specified, the reagents and methods involved in the examples are all commonly used in the art.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0029] Example 1 S1: Synthesis of (4-methoxyphenyl)-2-pyridyl ketone (compound II) Anhydrous aluminum chloride (17.02 g, 126.39 mmol, 1.50 equiv.) and pyridine-2-formyl chloride hydrochloride (15.00 g, 84.26 mmol, 1.00 equiv.) were added sequentially to a dry 250 mL three-necked flask. Nitrogen gas was then added, followed by the addition of 75 mL of 1,2-dichloroethane. The mixture was stirred for 0.5 h, then heated to 55°C. Anisole (13.15 g, 126.39 mmol, 1.50 equiv.) was slowly added dropwise over approximately 0.5 h, and the reaction continued for another 4 h. TLC monitoring showed that the starting materials were essentially completely converted. After cooling to room temperature, the reaction solution was added dropwise to 150 mL of ice water. The pH was adjusted to 4-5 with 10% sodium hydroxide aqueous solution. The mixture was filtered, and the filtrate was separated. The aqueous phase was further extracted with dichloromethane (30 mL × 2). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure to obtain 15.55 g of grayish-white solid. The crude product yield was 86.6% (based on pyridine-2-formyl chloride hydrochloride).

[0030] S2: Synthesis of α-(4-methoxyphenyl)-2-pyridylmethanol (compound III) To a 100 mL three-necked flask, 40 mL of methanol, compound II (8.40 g, 39.38 mmol, 1.00 equiv.), and potassium borohydride (0.88 g, 15.75 mmol, 0.40 equiv.) were added sequentially, and the mixture was stirred for 1 h. TLC monitoring showed that the starting material was essentially completely converted. 56 mL of water was added dropwise to the reaction mixture, and the mixture was stirred in an ice bath for 0.5 h. The mixture was then filtered, and the filter cake was washed with 4 mL of methanol. The filter cake was then dried under vacuum to obtain 8.12 g of a light brown solid, with a crude product yield of 95.9%.

[0031] S3: Synthesis of 4-[(4-methoxyphenyl)-2-pyridinemethyl]phenol (compound IV) To a 250 mL three-necked flask, compound III (9.60 g, 44.60 mmol, 1.00 equiv.), phenol (4.71 g, 49.06 mmol, 1.10 equiv.), and 48 mL of nitrobenzene were added sequentially. The mixture was transferred to an ice bath and cooled to 0°C with stirring. Concentrated sulfuric acid (13.39 g, 133.8 mmol, 3.00 equiv.) was added dropwise over approximately 0.5 h. The reaction mixture was then transferred to room temperature and stirred for 1 h. TLC monitoring showed that the starting materials were essentially completely converted. The reaction mixture was added dropwise to 48 mL of ice water, and the pH was adjusted to neutral by adding 10% sodium hydroxide aqueous solution. A solid precipitated, which was filtered. The filter cake was washed sequentially with 32 mL of water and 16 mL of dichloromethane. The filter cake was then dried under vacuum at 50°C to obtain 12.03 g of white solid, with a crude product yield of 92.6%.

[0032] Synthesis of S4: 4,4'-Dihydroxydiphenyl(2-pyridyl)methane (Compound I) Compound IV (10.00 g, 34.32 mmol, 1.0 equiv.) and 40% hydrobromic acid aqueous solution (13.88 g, 68.64 mmol, 2.0 equiv.) were added sequentially to a 50 mL three-necked flask. A reflux apparatus was added, and the mixture was stirred and heated to 100°C. The reaction was allowed to proceed for 3 h, and TLC monitoring showed that the starting material was essentially completely converted. The mixture was then cooled to 50°C, and the pH was adjusted to neutral by slowly adding 10% sodium hydroxide aqueous solution. The mixture was stirred in an ice-water bath for 0.5 h, filtered, and the filter cake was washed with water (20 mL × 2) to obtain the crude product. The crude product was purified by acetone and water, and then dried under vacuum at 50 °C to obtain 7.69 g of gray solid (compound I), with a yield of 80.9%.

[0033] Comparative Example 1 S1: Synthesis of (4-methoxyphenyl)-2-pyridyl ketone (compound II) Anhydrous aluminum chloride (17.02 g, 126.39 mmol, 1.50 equiv.) and pyridine-2-carboxyl chloride hydrochloride (15.00 g, 84.26 mmol, 1.00 equiv.) were added sequentially to a dry 250 mL three-necked flask. Nitrogen gas was then added, followed by the addition of 75 mL of 1,2-dichloroethane. The mixture was stirred for 0.5 h, and then anisole (13.15 g, 126.39 mmol, 1.50 equiv.) was slowly added dropwise over approximately 0.5 h. The reaction was then continued at room temperature for 12 h. After cooling to room temperature, the reaction solution was added dropwise to 150 mL of ice water. The pH was adjusted to 4-5 with 10% sodium hydroxide aqueous solution. The mixture was separated, and the aqueous phase was further extracted with dichloromethane (30 mL × 2). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure to obtain 8.58 g of grayish-white solid. The crude product yield was 47.80%, and a large amount of the raw material was not converted (calculated as pyridine-2-formyl chloride hydrochloride).

[0034] Comparative Example 2 S1: Synthesis of (4-methoxyphenyl)-2-pyridyl ketone (compound II) Anhydrous aluminum chloride (17.02 g, 126.39 mmol, 1.50 equiv.) and pyridine-2-carboxyyl chloride hydrochloride (15.00 g, 84.26 mmol, 1.00 equiv.) were added sequentially to a 250 mL dry three-necked flask. Nitrobenzene was added after purging with nitrogen. The mixture was stirred for 0.5 h, then heated to 90°C. Anisole (13.15 g, 126.39 mmol, 1.50 equiv.) was slowly added dropwise over approximately 0.5 h, and the reaction continued for another 4 h. TLC monitoring showed that the starting materials were essentially completely converted. After cooling to room temperature, the reaction solution was added dropwise to 150 mL of ice water. The pH was adjusted to 4-5 with 10% sodium hydroxide aqueous solution. The mixture was separated, and the aqueous phase was further extracted with dichloromethane (30 mL × 2). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. After column chromatography, 8.46 g of grayish-white solid was obtained, with a yield of 47.10%. A large number of impurities (calculated as pyridine-2-formyl chloride hydrochloride) were present.

[0035] Comparative Example 3 Synthesis of S4: 4,4'-Dihydroxydiphenyl(2-pyridyl)methane (Compound I) Compound IV (10.00 g, 34.32 mmol, 1.0 equiv.), 50 mL of acetic acid, and concentrated hydrochloric acid (11.9 mL, 137.28 mmol, 4.0 equiv.) were added sequentially to a 100 mL three-necked flask. A reflux reflux apparatus was added, and the mixture was stirred and heated to 100°C for 5 h. The mixture was then cooled to 50°C, and the pH was adjusted to neutral by slowly adding 10% sodium hydroxide aqueous solution. The mixture was stirred in an ice-water bath for 0.5 h, filtered, and the filter cake was washed with water (20 mL × 2) to obtain a crude product. The crude product was purified by acetone and water, and dried under vacuum at 50°C to obtain 4.70 g of gray solid (compound I), with a yield of 49.46%. A significant portion of the starting material remained unconverted.

[0036] In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, this specification should be considered illustrative rather than restrictive.

Claims

1. A method for synthesizing 4,4'-(2-pyridinemethyl)bisphenol, characterized in that, The method includes the following steps: (1) 2-pyridinecarboxyl chloride hydrochloride was subjected to Friedel-Crafts acylation with phenyl ether to give compound II; (2) Compound II is reacted with reducing agents such as sodium borohydride or potassium borohydride to obtain compound III; (3) Compound III was subjected to Friedel-Crafts alkylation with phenol to obtain compound IV; (4) Compound IV is dealkylated in the reducing agent hydrobromic acid or hydroiodic acid to give compound I 4,4'(2-pyridinemethyl)bisphenol; 2. The synthesis method according to claim 1, characterized in that, The solvent used in step (1) is selected from dichloromethane, chloroform, dichloroethane or trichloroethane; the catalyst used is one or more of anhydrous aluminum trichloride, ferric chloride, zinc chloride, titanium tetrachloride, boron trichloride or boron trifluoride; the reaction temperature is 40 to 85°C; the reaction time is 1 to 10 h.

3. The synthesis method according to claim 2, characterized in that, The molar ratio of 2-pyridinecarboxyl chloride hydrochloride, phenyl ether, and catalyst is 1:1.1-1.5:1.5-2.

5.

4. The synthesis method according to claim 1, characterized in that, The solvent used in step (2) is selected from methanol, ethanol, isopropanol and tetrahydrofuran; the molar ratio of compound II to reducing agent is 1:0.3-0.5; the reaction temperature is 0-30℃; and the reaction time is 0.5-5 h.

5. The synthesis method according to claim 1, characterized in that, The organic solvent in step (3) is one or more of dichloromethane, chloroform, chlorobenzene, nitrobenzene, dichloroethane, or trichloroethane; the catalyst used is one or more of concentrated sulfuric acid, hydrochloric acid, anhydrous aluminum trichloride, ferric chloride, zinc chloride, titanium tetrachloride, boron trichloride, or boron trifluoride; the molar ratio of compound III, phenol, and catalyst is 1:1.0-1.3:2.0-4.0; the reaction temperature is 0-30℃; and the reaction time is 0.5-2.0h.

6. The synthesis method according to claim 1, characterized in that, In step (4), the molar ratio of compound IV to reducing agent is 1:2.0-5.0; the reaction temperature is 80-110℃; and the reaction time is 2.0-8.0 h.

7. The synthesis method according to any one of claims 1 to 6, characterized in that, Step (1) further includes: adding the reaction solution dropwise to ice water to quench it, adjusting the pH value with an alkaline reagent, solvent extraction and concentrating the extract; Step (2) further includes: quenching with water, precipitating solids, and filtration; Step (3) further includes: adding the reaction solution dropwise into ice water, adjusting the pH value with an alkaline reagent to precipitate the solid, and then filtering it; Step (4) further includes: cooling, adjusting the pH value with an alkaline reagent to precipitate the solid, and then filtration.

8. The synthesis method according to any one of claims 1 to 6, characterized in that, The method specifically includes the following steps: (1) Add anhydrous aluminum chloride and 2-pyridinecarboxyl chloride hydrochloride to the solvent, raise the temperature to the reaction temperature, add phenyl ether dropwise to react, quench the reaction solution dropwise in ice water, adjust the pH value with an alkaline reagent, extract with solvent and concentrate the extract to obtain compound II. The extraction solvent is dichloromethane or dichloroethane. (2) Add compound II to an organic solvent, and then add sodium borohydride or potassium borohydride as a reducing agent. After the reaction is complete, add water to quench the reaction, precipitate the solid, and filter to obtain compound III. (3) Dissolve compound III and phenol in an organic solvent, add concentrated sulfuric acid dropwise in an ice bath to carry out the reaction, after the reaction is completed, add the reaction solution dropwise to ice water, adjust the pH value with an alkaline reagent to precipitate the solid, and then filter to obtain compound IV; (4) Add reducing agent hydrobromic acid or hydroiodic acid to compound IV to react, cool down, adjust the pH value with alkaline reagent to precipitate solid, and then filter to obtain compound I 4,4' (2-pyridinemethyl)bisphenol.

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