Preparation of resveratrol derivative based on ferrocene skeleton

Abstract

The invention relates to preparation of a resveratrol derivative based on a ferrocene skeleton, belongs to the field of pharmaceutical chemistry synthesis, and provides a preparation method of a novel ferrocene substituted resveratrol derivative. Aiming at the problems of poor water solubility and low bioavailability of resveratrol, the yield and efficiency are improved by optimizing zinc-copper coupling reaction conditions. The method comprises the following steps: firstly, reacting ferrocenecarboxylic acid with an acylating agent to generate ferrocene formyl chloride; then reacting the product with substituted benzene under the catalysis of Lewis acid to form substituted phenyl ferrocenyl ketone; then carrying out deprotection treatment on the intermediate containing methoxyl; finally, coupling of the high-valence titanium metal compound, the substituted phenyl ferrocenyl ketone and the substituted benzaldehyde is achieved under the reduction condition, and synthesis of a target product is completed. The method is mild in condition, simple and convenient to operate, good in economy and suitable for large-scale production. The synthesized ferrocene substituted resveratrol derivative is expected to become a novel anticancer drug or health care product component, and provides a new way for the treatment of related diseases. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the field of organic chemical synthesis, and in particular to a method for preparing two novel ferrocene-substituted resveratrol derivatives. Background Art

[0002] Resveratrol (RES) is a non-flavonoid polyphenol compound that was first isolated from the roots of Veratrum pubescens. It is found in high concentrations in human foods such as grapes, knotweed and peanuts. It has a broad spectrum of anticancer activity and has good cytotoxic activity against liver cancer, breast cancer, colon cancer, lung cancer and leukemia. Although resveratrol exhibits extensive and significant antitumor activity, it still has many disadvantages, such as poor water solubility, low bioavailability, fast metabolism, chemical stability and low activity. Therefore, it is urgent to develop resveratrol derivatives with better solubility, higher stability and better activity.

[0003] Resveratrol and its derivatives have a variety of preparation methods. The literature (RSC Adv., 2022, 12, 15885) reviews in detail the preparation of double bonds using the McMurray coupling reaction. This method has the characteristics of mild reaction conditions, economical and readily available raw materials, wide application range, and low requirements for raw materials. The present invention uses this method as the core to synthesize the final product. At the same time, the present invention optimizes this method, using zinc-copper couple instead of zinc powder as a catalyst. The presence of copper can activate zinc powder, enhance reaction activity, and ultimately improve yield. Summary of the invention

[0004] The purpose of the present invention is to provide a novel ferrocene-substituted resveratrol derivative and a preparation method thereof. The technical scheme is as follows:

[0005] The first aspect of the present invention provides compounds represented by the following formulas (I) and (II):

[0006]

[0007] The second aspect of the present invention provides a method for preparing the above-mentioned compound with mild conditions, simple operation and atom economy, which is achieved by the following reaction and purification steps:

[0008] Preparation method of compound (I):

[0009] (1) mixing ferrocenecarboxylic acid, an acylating agent, a catalyst and a solvent, protecting with an inert gas, and stirring at room temperature to obtain ferrocenecarboxylic acid chloride;

[0010] (2) Adding a solvent, a substituted benzene and a Lewis acid catalyst to the reaction system in sequence, adding ferrocenecarbonyl chloride dropwise at low temperature, protecting with an inert gas, and stirring at room temperature; after the reaction, slowly pouring the reaction solution into ice water to quench, adding commercially available hydrochloric acid to adjust the pH to acidic, standing, extracting, combining the organic phases, adding a dehydrating agent, filtering, and separating with a silica gel chromatography column to obtain substituted phenyl ferrocene ketone (compounds 3 and 4);

[0011] (3) Add (4-methoxy)-phenylferrocenyl ketone (compound 3) and a solvent to the reaction system in sequence, add boron tribromide dropwise at low temperature, protect with inert gas, and stir at room temperature; after the reaction, slowly add methanol dropwise to the system at low temperature to quench, let stand, extract, combine the organic phases, add a dehydrating agent, filter, and separate using a silica gel chromatography column to obtain (4-hydroxy)-phenylferrocenyl ketone (compound 5).

[0012] (4) Add a high-valent titanium metal compound dropwise to a strong reducing agent and a solvent at low temperature, protect with an inert gas, stir, and heat for coupling reaction. After a period of reaction, low-valent titanium is obtained, and the temperature is lowered. A substituted phenyl ferrocenyl ketone and a substituted benzaldehyde are added to the system, and the heating coupling reaction is continued. After the reaction, the temperature is lowered, dilute hydrochloric acid is added to quench, the mixture is allowed to stand, extraction is performed, the organic phases are combined, saturated sodium bicarbonate is added, the mixture is allowed to stand, the liquids are separated, a dehydrating agent is added, filtering is performed, and separation is performed using a silica gel chromatography column to obtain a ferrocenyl-substituted resveratrol derivative (1a-1n).

[0013] The acylating agent in step (1) is oxalyl chloride or thionyl chloride. Considering the safety of the experiment, the present invention selects oxalyl chloride as the acylating agent; the catalyst is N,N-dimethylformamide or pyridine; the solvent is dichloromethane; and the inert gas is nitrogen.

[0014] The molar ratio of ferrocenecarboxylic acid to the acylating agent and the catalyst in step (1) is 1:1:0.05.

[0015] The solvent in step (2) is dichloromethane; the substituted benzenes are anisole and isophenylene dimethyl ether; the Lewis acid catalyst is aluminum chloride; the inert gas is nitrogen; the dehydrating agent is anhydrous sodium sulfate; the obtained substituted phenyl ferrocenyl ketones are (4-methoxy)-phenyl ferrocenyl ketone and (2,4-dimethoxy)-phenyl ferrocenyl ketone.

[0016] The low-temperature dropwise addition in step (2) is a 0-5°C ice water bath; the temperature of the ice water is 0-5°C.

[0017] In step (2), the molar ratio of the substituted benzene, the catalyst and the ferrocenecarbonyl chloride is 1:1.2:1.

[0018] The extraction in step (2) is performed by using dichloromethane and water, and the solvent ratio of the chromatography column separation is petroleum ether:ethyl acetate (v / v) = 30:1.

[0019] The solvent in step (3) is dichloromethane; the inert gas is nitrogen; and the dehydrating agent is anhydrous sodium sulfate.

[0020] The low temperature in step (3) is -78°C.

[0021] The molar ratio of (4-methoxy)-phenylferrocenyl ketone to boron tribromide in step (3) is 1:6.

[0022] The extraction in step (3) is performed by extraction with dichloromethane and water, and the solvent ratio of the chromatography column separation is petroleum ether:ethyl acetate (v / v) = 5:1.

[0023] The strong reducing agent in step (4) is zinc copper couple or zinc powder; the solvent is anhydrous tetrahydrofuran; the high-valent titanium metal compound is titanium tetrachloride; the inert gas is nitrogen; the substituted phenyl ferrocenyl ketones are compounds 3, 4 and 5; the substituted benzaldehydes are 3,5-dimethoxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 2,4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 2,4,5-trimethoxybenzaldehyde, 2,3,4-trimethoxybenzaldehyde and 2,4,6-trimethoxybenzaldehyde; and the dehydrating agent is anhydrous sodium sulfate.

[0024] The low temperature and cooling in step (4) are both ice water baths (0-5°C); the coupling reaction temperature is 66-70°C.

[0025] The time for obtaining low-valent titanium in step (4) is 2-2.5 hours; the total time for the coupling reaction is 8-10 hours.

[0026] In step (4), the molar ratio of the strong reducing agent to the high-valent titanium metal compound is 2:1.

[0027] The molar ratio of the substituted phenyl ferrocenyl ketone to the substituted benzaldehyde in step (4) is 1:1.

[0028] The extraction in step (4) is performed by extraction with ethyl acetate and water; the solvent ratio of the chromatography column separation is petroleum ether:ethyl acetate (v / v) = 10:1 to 100:1.

[0029] Preparation method of compound (II):

[0030] (1) Add a catalyst to ferrocenecarboxylic acid and p-hydroxybenzaldehyde, protect with inert gas, and stir at room temperature; after the reaction, add a saturated sodium bicarbonate solution, extract, combine the organic phases, add a dehydrating agent, filter, and separate using a silica gel chromatography column to obtain ferrocenecarboxylic acid-(4-formaldehyde)-phenyl ester (Compound 6).

[0031] (2) Add a high-valent titanium metal compound dropwise to a strong reducing agent and a solvent at low temperature, protect with an inert gas, stir, and heat for coupling reaction. After a period of reaction, low-valent titanium is obtained. The temperature is lowered, and 4-formylphenyl ferrocene carboxylate (compound 6) and substituted benzaldehyde are added to the system, and the heating coupling reaction is continued. After the reaction, the temperature is lowered, dilute hydrochloric acid is added to quench, the mixture is allowed to stand, extraction is performed, the organic phases are combined, saturated sodium bicarbonate is added, the mixture is allowed to stand, the liquids are separated, a dehydrating agent is added, filtering is performed, and separation is performed using a silica gel chromatography column to obtain ferrocene-substituted resveratrol derivatives (2a-2j).

[0032] The catalyst in step (1) is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP); the inert gas is nitrogen; the dehydrating agent is anhydrous sodium sulfate; and the solvent is dichloromethane.

[0033] The molar ratio of ferrocenecarboxylic acid, p-hydroxybenzaldehyde, EDCI and DMAP in step (1) is 1:1:1.5:0.05.

[0034] The extraction in step (1) is performed by extraction with dichloromethane and water; the solvent ratio of the chromatography column separation is petroleum ether:ethyl acetate (v / v) = 20:1.

[0035] The strong reducing agent in step (2) is zinc copper couple or zinc powder; the solvent is anhydrous tetrahydrofuran; the high-valent titanium metal compound is titanium tetrachloride; the inert gas is nitrogen; the substituted benzaldehyde is 3,5-dimethoxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 2,4,5-trimethoxybenzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, 3,5-dimethylbenzaldehyde, p-isopropylbenzaldehyde and p-tert-butylbenzaldehyde; and the dehydrating agent is anhydrous sodium sulfate.

[0036] The low temperature and cooling in step (2) are both ice water baths (0-5°C); the coupling reaction temperature is 66-70°C.

[0037] The time for obtaining low-valent titanium in step (2) is 2-2.5 hours; the total time for the coupling reaction is 8-10 hours.

[0038] In step (2), the molar ratio of the strong reducing agent to the high-valent titanium metal compound is 2:1.

[0039] In step (2), the molar ratio of 4-formylphenyl ferrocene carboxylate to substituted benzaldehyde is 1:1.

[0040] The extraction in step (2) is performed by using ethyl acetate and water; the solvent ratio of the chromatography column separation is petroleum ether:ethyl acetate (v / v) = 50:1 to 100:1.

[0041] In the present invention, unless otherwise specified, the terms used herein have the meanings commonly understood by those skilled in the art. The following provides definitions and explanations of the relevant terms.

[0042] Herein, the term "reaction system" can be understood as the sum of all substances including reactants, products, solvents, etc. DETAILED DESCRIPTION

[0043] The technical solution of the present invention will be described below in conjunction with specific embodiments. Unless otherwise specified, the raw materials and equipment used in the specific embodiments of the present invention are all known products, which are obtained by purchasing commercial products.

[0044] List of abbreviations used in the following examples

[0045] CH2Cl2: dichloromethane

[0046] DMF: N,N-dimethylformamide

[0047] EA: Ethyl acetate

[0048] PE: Petroleum ether

[0049] Na2SO4: Sodium sulfate

[0050] THF: Tetrahydrofuran

[0051] EDCI: 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride

[0052] DMAP: 4-dimethylaminopyridine

[0053] Example 1: Synthesis of ferrocenecarbonyl chloride

[0054]

[0055] Take a 250mL three-necked flask, add 0.8g (0.0035mol) of ferrocenecarboxylic acid, under nitrogen protection, pump and inflate 3 times, inject 200mL of CH2Cl2 with a 50mL syringe, add 0.35mL of oxalyl chloride (2.0M dissolved in CH2Cl2), and finally add 2 drops of DMF, and stir at room temperature. After the reaction is completed according to TLC (4-6h), directly vacuum concentrate the reaction system, evaporate the remaining oxalyl chloride, add CH2Cl2 to dissolve, and then add petroleum ether for recrystallization. The precipitated solid is ferrocenecarboxylic acid, filter, collect the filtrate, and evaporate the solvent to obtain orange-red solid ferrocenecarboxylic acid, with a yield of 73%.

[0056] Example 2: Synthesis of ferrocenyl-(4-methoxy)-phenyl ketone

[0057]

[0058] Take a 250mL three-necked flask, add 0.32g (0.0024mol) of aluminum chloride, under nitrogen protection, evacuate and inflate 3 times, inject 120mL of CH2Cl2 with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, add 0.22mL (0.0020mol) of anisole, and finally slowly add a CH2Cl2 solution of ferrocenecarbonyl chloride (0.5g, 0.0020mol) dropwise. After the addition is completed, stir at room temperature. After the reaction was completed as judged by TLC (8h), the reaction solution was poured into ice water (0-5°C), commercially available hydrochloric acid was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=30:1) to obtain a red solid ferrocenyl-(4-methoxy)-phenyl ketone with a yield of 80%.

[0059] mp67-70℃; 1 H NMR (500MHz, Chloroform-d) δ7.96 (d, J=8.3Hz, 2H), 6.96 (d, J=7.8Hz, 2H), 4.92 (s, 2H), 4.57 (s, 2H), 4.22 (s, 5H), 3.89 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ196.43, 162.55, 132.11, 130.77, 114.16, 78.89, 72.68, 71.54, 70.41, 55.89; HRMS (ESI) m / z calcd for C 18 H 16 FeO2[M+H] + :320.0500, found:320.0502.

[0060] Example 3: Synthesis of ferrocenyl-(2,4-dimethoxy)-phenyl ketone

[0061]

[0062] Take a 250mL three-necked flask, add 0.32g (0.0024mol) of aluminum chloride, under nitrogen protection, evacuate and inflate 3 times, inject 120mL of CH2Cl2 with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, add 0.28mL (0.0020mol) of isophenyl dimethyl ether, and finally slowly add a CH2Cl2 solution of ferrocenecarbonyl chloride (0.5g, 0.0020mol) dropwise. After the addition is completed, stir at room temperature. After the reaction was completed as judged by TLC (8h), the reaction solution was poured into ice water (0-5°C), commercially available hydrochloric acid was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain a red solid ferrocenyl-(2,4-dimethoxy)-phenyl ketone with a yield of 90%.

[0063] mp118-120℃; 1 H NMR (500MHz, DMSO-d6) δ7.39 (d, J=8.3Hz, 1H), 6.65 (s, 1H), 6.62 (d, J=8.3Hz, 1H), 4.60 (d, J=18.7Hz, 4H), 4.19 (s, 5H), 3.84 (s, 3H), 3.74 (s, 3H); 13 CNMR (126MHz, DMSO-d6) δ197.88, 162.35, 158.24, 129.94, 123.48, 105.26, 99.21, 80.01, 72.64, 70.97, 70.23, 55.91, 55.88; HRMS (ESI) m / zcalcd for C 19 H 18 FeO3[M+H] + :350.0605, found:350.0609.

[0064] Example 4: Synthesis of ferrocenyl-(4-hydroxy)-phenyl ketone

[0065]

[0066] Take a 250mL three-necked flask, add 30.5g (0.0016mol) of the compound, under nitrogen protection, pump and inflate 3 times, inject 220mL of CH2Cl2 into the syringe, place the reaction system at -78°C and stir, slowly add 0.90mL (0.0096mol) of boron tribromide, after the addition is complete, place it at room temperature and stir. According to TLC, after the reaction is completed (2h), place the reaction system at -78°C, add methanol, evaporate the solvent, extract with water and CH2Cl2, combine the organic phases, add anhydrous Na2SO4 to dry the organic phase, filter, evaporate CH2Cl2, and obtain a mixture solid. Finally, separate and purify it by silica gel column chromatography (PE: EA = 5: 1) to obtain a red solid ferrocenyl-(4-hydroxy)-phenyl ketone with a yield of 85%.

[0067] mp160-162℃; 1 H NMR (500MHz, DMSO-d6) δ10.18 (s, 1H), 7.85 (d, J = 8.6Hz, 2H), 6.88 (d, J = 8.5Hz, 2H), 4.82 (s, 2H), 4.63 (s, 2H), 4.23 (s, 5H); 13 C NMR (126MHz, DMSO-d6) δ196.18, 161.40, 131.05, 130.64, 115.49, 79.16, 72.44, 71.53, 70.36; HRMS (ESI) m / z calcdfor C 17 H 14 FeO2[M+H] + :306.0343, found:306.0348.

[0068] Example 5: Synthesis of (E)-5-(2-ferrocenyl-2-(4-hydroxyphenyl)vinyl)-1,3-dimethoxybenzene

[0069]

[0070] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 5 (0.5g, 0.0016mol) and 3,5-dimethoxybenzaldehyde (0.27g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain a light red solid 1a with a yield of 36%.

[0071] mp150-153℃; 1 H NMR (500MHz, DMSO-d6) δ9.48 (s, 1H), 7.07 (d, J = 8.3Hz, 2H), 6.86 (s, 2H), 6. 85(s, 1H), 6.20(s, 1H), 6.13(s, 2H), 4.29(s, 4H), 4.15(s, 5H), 3.52(s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.25, 157.05, 141.51, 139.61, 130.50, 129.20, 123.95, 115.98, 11 5.06, 107.60, 107.21, 99.04, 97.93, 88.47, 69.67, 69.30, 68.85, 66.94, 55.17; HRMS (ESI) m / z calcd for C 26 H 24 FeO3[M+H] + :440.1075, found: 440.1117.

[0072] Example 6: Synthesis of (E)-5-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,3-dimethoxybenzene

[0073]

[0074] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 3,5-dimethoxybenzaldehyde (0.27g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=50:1) to obtain a red solid 1b with a yield of 38%.

[0075] mp114-118℃; 1 H NMR (500MHz, Chloroform-d) δ7.23 (d, J=8.0Hz, 2H), 6.95 (d, J=8.1Hz, 2H), 6.75 (s, 1H), 6.19 (s, 1H), 6.11 (s, 2H), 4.36 (d, J=17.2Hz, 4H), 4.21 (s, 5H), 3.85 (s, 3H), 3.55 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.28, 158.95, 141.11, 139.49, 132.30, 130.64, 124.15, 11 4.61, 107.19, 99.18, 88.30, 69.69, 69.36, 68.47, 66.93, 55.60, 55.18; HRMS (ESI) m / z calcd for C 27 H 26 FeO3[M+H] + :454.1231, found:454.1233.

[0076] Example 7: Synthesis of (E)-4-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,2-dimethoxybenzene

[0077]

[0078] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 3,4-dimethoxybenzaldehyde (0.27g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=50:1) to obtain a red solid 1c with a yield of 41%.

[0079] mp145-149℃; 1 H NMR (500MHz, DMSO-d6) δ7.21 (d, J=8.2Hz, 2H), 7.05 (d, J=8.3Hz, 2H), 6.87 (s, 1H), 6.74 (d, J=8.4Hz, 1H), 6.60 ( d, J=6.3Hz, 1H), 6.39 (s, 1H), 4.27 (dd, J=6.7, 1.9Hz, 4H), 4.15 (s, 5H), 3.80 (s, 3H), 3.67 (s, 3H), 3.36 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ158.88, 148.30, 147.74, 138.04, 132.55, 130.85, 130.58, 124.07, 122 .36, 114.72, 112.21, 111.83, 88.94, 69.60, 69.07, 66.58, 55.83, 55.59, 55.05; HRMS (ESI) m / z calcd for C 27 H 26 FeO3[M+H] + :454.1231, found:454.1259.

[0080] Example 8: Synthesis of (E)-4-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,3-dimethoxybenzene

[0081]

[0082] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 2,4-dimethoxybenzaldehyde (0.27g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=60:1) to obtain a red solid 1d with a yield of 33%.

[0083] mp89-92℃; 1 H NMR (500MHz, DMSO-d6) δ7.15 (d, J=8.5Hz, 2H), 7.00 (s, 1H), 6.93 (d, J=8.5Hz, 2H), 6.50 (d, J=8.7Hz, 2H), 6 .17(dd,J=8.6,2.5Hz,1H),4.26(s,2H),4.21(s,2H),4.16(s,5H),3.82(s,3H),3.77(s,3H),3.68(s,3H);1 3 C NMR (126MHz, DMSO-d6) δ159.51, 158.55, 158.43, 137.61, 132.56, 130.94, 130.11, 119.25, 11 9.18, 114.23, 104.97, 98.58, 89.15, 69.76, 68.86, 66.93, 56.06, 55.53, 55.42; HRMS (ESI) m / z calcd forC 27 H 26 FeO3[M+H] + :454.1231, found:454.1227.

[0084] Example 9: Synthesis of (E)-5-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,2,3-trimethoxybenzene

[0085]

[0086] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 3,4,5-trimethoxybenzaldehyde (0.31g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=30:1) to obtain a red solid 1e with a yield of 44%.

[0087] mp100-102℃; 1 H NMR (500MHz, DMSO-d6) δ7.23 (d, J = 8.6Hz, 2H), 7.08 (d, J = 8.6Hz, 2H), 6.87 (s, 1H), 6.2 4(s, 2H), 4.29(d, J=11.8Hz, 4H), 4.16(s, 5H), 3.80(s, 3H), 3.57(s, 3H), 3.48(s, 6H); 13 C NMR (126MHz, DMSO-d6) δ158.99, 152.64, 139.78, 136.36, 133.17, 132.41, 130.78, 124.07, 114.78, 106.65, 88.53, 69.64, 69.27, 66.70, 60.38, 55.67; HRMS (ESI) m / z calcd for C 28 H 28 FeO4[M+H] + :484.1337, found:484.1339.

[0088] Example 10: Synthesis of (E)-5-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,2,4-trimethoxybenzene

[0089]

[0090] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 2,4,5-trimethoxybenzaldehyde (0.31g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a solid mixture, and finally silica gel column chromatography (PE:EA=40:1) was used for separation and purification to obtain a red solid 1f with a yield of 41%.

[0091] mp107-110℃; 1 H NMR (500MHz, DMSO-d6) δ7.19 (d, J = 8.4 Hz, 2H), 7.04 (s, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.59 (s, 1H), 6.13 (s, 1H), 4.28 (s, 2H), 4.23 (s, 2H), 4.16 (s, 5H), 3.82 (s, 3H), 3.77 (s, 3H), 3.74 (s, 3H), 3.15 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ158.78, 152.01, 148.58, 142.17, 137.62, 132.71, 131.04, 118.73, 117.8 5, 114.49, 113.49, 98.48, 89.05, 69.72, 68.95, 66.77, 57.01, 56.06, 55.59, 55.50; HRMS (ESI) m / z calcd forC 28 H 28 FeO4[M+H] + :484.1337, found:484.1322.

[0092] Example 11: Synthesis of (E)-4-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,2,3-trimethoxybenzene

[0093]

[0094] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 2,3,4-trimethoxybenzaldehyde (0.31g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=50:1) to obtain 1 g of red solid with a yield of 38%.

[0095] mp79-84℃; 1 H NMR (500MHz, DMSO-d6) δ7.17 (d, J = 8.1 Hz, 2H), 7.01 (s, 1H), 6.96 (d, J = 8.1 Hz, 2H), 6.45 (d, J = 8.8 Hz, 1H), 6.2 6 (d, J=8.8Hz, 1H), 4.27 (d, J=12.0Hz, 4H), 4.16 (s, 5H), 3.86 (s, 3H), 3.79 (s, 3H), 3.73 (s, 3H), 3.68 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ158.67, 152.23, 152.08, 142.10, 139.06, 132.28, 130.91, 129.66, 124.53, 124.17 , 118.57, 114.34, 113.69, 107.96, 88.62, 69.68, 69.07, 67.13, 61.46, 60.89, 56.15, 55.44; HRMS (ESI) m / z calcd for C 28 H 28 FeO4[M+H] + :484.1337, found:484.1353.

[0096] Example 12: Synthesis of (E)-6-(2-ferrocenyl-2-(4-methoxyphenyl)vinyl)-1,3,5-trimethoxybenzene

[0097]

[0098] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 3 (0.5g, 0.0016mol) and 2,4,6-trimethoxybenzaldehyde (0.31g, 0.0016mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally silica gel column chromatography (PE:EA=80:1) was used for separation and purification to obtain a red solid 1h, with a yield of 29%.

[0099] mp107-111℃; 1 H NMR (500MHz, DMSO-d6) δ7.03 (d, J = 8.7Hz, 2H), 6.77 (d, J = 8.8Hz, 2H), 6.59 (s, 1H), 6.0 6 (s, 2H), 4.26 (d, J = 16.7Hz, 4H), 4.19 (s, 5H), 3.71 (s, 3H), 3.70 (s, 3H), 3.51 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.30, 158.17, 158.07, 140.01, 133.74, 129.95, 116.89, 113.61, 11 3.04, 108.77, 91.24, 90.97, 87.99, 69.97, 68.67, 67.44, 55.59, 55.50, 55.33; HRMS (ESI) m / z calcd for C 28 H 28 FeO4[M+H] + :484.1337, found:484.1335.

[0100] Example 13: Synthesis of (E)-5-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,3-dimethoxybenzene

[0101]

[0102] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 3,5-dimethoxybenzaldehyde (0.24g, 0.0014mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a solid mixture, and finally silica gel column chromatography (PE:EA=40:1) was used for separation and purification to obtain a red solid 1i with a yield of 43%.

[0103] mp81-85℃; 1 H NMR (500MHz, DMSO-d6) δ7.08 (d, J=8.2Hz, 1H), 6.89 (s, 1H), 6.68 (s, 1H), 6.65 (d, J=8.2Hz, 1H), 6.20 (s, 1H), 6.16 (s, 2H), 4.57 (s, 1H), 4.30 (s, 1H), 4.20 (s, 1H), 4.12 (s, 5H), 3.93 (s, 1H), 3.82 (s, 3H), 3.64 (s, 3H), 3.52 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.64, 160.31, 158.13, 139.79, 137.90, 131.24, 125.06, 121.26, 106.48, 1 05.65, 99.31, 99.25, 88.32, 69.62, 69.05, 68.91, 68.25, 65.49, 55.81, 55.74, 55.16; HRMS (ESI) m / z calcd for C 28 H 28 FeO4[M+H] + :484.1337, found:484.1323.

[0104] Example 14: Synthesis of (E)-4-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,2-dimethoxybenzene

[0105]

[0106] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 3,4-dimethoxybenzaldehyde (0.24g, 0.0014mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=40:1) to obtain a red solid 1j with a yield of 44%.

[0107] mp127-130℃; 1 H NMR (500MHz, DMSO-d6) δ7.08 (d, J = 8.2Hz, 1H), 6.87 (s, 1H), 6.74 (d, J = 8.4Hz, 1H), 6.69 (s, 1H), 6.66 (d, J = 8.1Hz, 1H), 6.62 (d, J = 8.4Hz, 1H), 6.43(s, 1H), 4.54(s, 1H), 4.27(s, 1H), 4.19(s, 1H), 4.12(s, 5H), 3.93(s, 1H), 3.82(s, 3H), 3.67(s, 3H), 3.64(s, 3H), 3.38(s, 3H); 13 C NMR (126MHz, DMSO-d6) δ160.59, 158.30, 148.38, 147.71, 134.71, 131.47, 130.95, 124.90, 121.93, 121.42, 111.82, 111.33, 105.73, 99.37, 88.99, 69.53, 68.77, 68.64, 67.86, 65.22, 55.82, 55.79, 55.74, 55.04; HRMS(ESI)m / zcalcd for C 28 H 28 FeO4[M+H] + :484.1337, found:484.1428.

[0108] Example 15: Synthesis of (E)-5-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,2,3-trimethoxybenzene

[0109]

[0110] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 3,4,5-trimethoxybenzaldehyde (0.28g, 0.0014mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally silica gel column chromatography (PE:EA=30:1) was used for separation and purification to obtain a red solid 1k with a yield of 48%.

[0111] mp46-50℃; 1 H NMR (500MHz, DMSO-d6) δ7.10 (d, J=8.1Hz, 1H), 6.87 (s, 1H), 6.70 (s, 1H), 6.68 (d, J=8.2Hz, 1H), 6.28 (s, 2H), 4.55 (s, 1 H), 4.29 (d, J = 3.7Hz, 1H), 4.20 (s, 1H), 4.13 (s, 5H), 3.94 (s, 1H), 3.81 (s, 3H), 3.66 (s, 3H), 3.57 (s, 3H), 3.50 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.70, 158.26, 152.68, 136.53, 136.33, 133.51, 131.39, 124.88, 121.27, 105. 96, 105.79, 99.34, 88.57, 69.57, 68.96, 68.83, 68.07, 65.27, 60.37, 55.83, 55.80, 55.67; HRMS (ESI) m / z calcd for C 29 H 30 FeO5[M+H]+ :514.1443, found:514.1454.

[0112] Example 16: Synthesis of (E)-5-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,2,4-trimethoxybenzene

[0113]

[0114] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 2,4,5-trimethoxybenzaldehyde (0.28g, 0.0014mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1 M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=30:1) to obtain a red solid 1l with a yield of 46%.

[0115] mp83-85℃; 1 H NMR (500MHz, DMSO-d6) δ7.09 (s, 1H), 7.03 (d, J = 8.2Hz, 1H), 6.65 (s, 1H), 6.60 (d, J = 8.4Hz, 1H), 6.59 (s, 1H), 6.22 (s, 1H), 4.45 (s, 1H), 4.25 (s, 1H), 4.17 (s, 1H), 4.11 (s, 5H), 3.90 (s, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.73 (s, 3H), 3.63 (s, 3H), 3.18 (s, 3H); 13C NMR (126MHz, DMSO-d6) δ160.49, 158.43, 151.69, 148.40, 142.36, 134.50, 131.57, 121.72, 119.44, 118.38, 111.98, 105.57, 99.22, 98.70, 89.14, 69.65, 68.67, 68.52, 67.84, 65.52, 57.22, 56.06, 55.76, 55.72, 55.37; HRMS (ESI) m / z calcd forC 29 H 30 FeO5[M+H] + :514.1443, found:514.1450.

[0116] Example 17: Synthesis of (E)-4-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,2,3-trimethoxybenzene

[0117]

[0118] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 2,3,4-trimethoxybenzaldehyde (0.28g, 0.0014mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally silica gel column chromatography (PE:EA=30:1) was used for separation and purification to obtain a red solid 1m with a yield of 40%.

[0119] mp89-91℃; 1H NMR (500MHz, DMSO-d6) δ7.04 (s, 2H), 6.61 (s, 1H), 6.58 (d, J = 8.3Hz, 1H), 6.44 (d, J = 8.9Hz, 1H), 6.31 (d, J = 8.8Hz, 1H), 4.49 ( s, 1H), 4.26 (s, 1H), 4.18 (s, 1H), 4.12 (s, 5H), 3.92 (s, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.73 (s, 3H), 3.67 (s, 3H), 3.60 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ160.34, 158.31, 152.19, 151.80, 142.03, 135.87, 131.42, 124.93, 123.01, 121.27, 119.44, 107.99, 105.43, 99.24, 88.57, 69.56, 68.78, 68.65, 68.02, 65.83, 61.44, 60.91, 56.12, 55.68, 55.58; HRMS (ESI) m / z calcd forC 29 H 30 FeO5[M+H] + :514.1443, found:514.1458.

[0120] Example 18: Synthesis of (E)-6-(2-ferrocenyl-2-(2,4-dimethoxyphenyl)vinyl)-1,3,5-trimethoxybenzene

[0121]

[0122] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 4 (0.5g, 0.0014mol) and 2,4,6-trimethoxybenzaldehyde (0.28g, 0.0014mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a solid mixture, and finally silica gel column chromatography (PE:EA=50:1) was used for separation and purification to obtain a red solid 1n with a yield of 20%.

[0123] mp115-120℃; 1 H NMR (500MHz, DMSO-d6) δ6.78 (d, J = 8.3 Hz, 1H), 6.61 (s, 1H), 6.44 (s, 1H), 6.34 (d, J = 8.3 Hz, 1H), 6.03 (s, 2H), 4.61 (s, 1H), 4.22 (s, 1H), 4.11 (s, 5H), 3.92 (s, 1H), 3.81 (s, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.53 (s, 3H), 3.51 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ160.02, 159.71, 158.31, 158.11, 138.02, 130.69, 122.76, 118.43, 108.89, 104.11, 98.58, 91 .39, 91.25, 90.79, 87.81, 69.91, 69.31, 68.40, 68.10, 66.28, 56.07, 55.50, 55.46, 55.42, 55.39; HRMS(ESI)m / zcalcd for C 29 H 30 FeO5[M+H] + :514.1443, found:514.1458.

[0124] Example 19: Synthesis of 4-formylphenyl ferrocene carboxylate

[0125]

[0126] Take a 250mL three-necked flask, add ferrocenecarboxylic acid 0.5g (0.0022mol) and p-hydroxybenzaldehyde 0.27g (0.0022mol), under nitrogen protection, pump and inflate 3 times, inject CH2Cl2 150mL with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add EDCI 0.63g (0.033mol) and DMAP 0.027g (0.0002mol) dropwise, and stir at room temperature. After the reaction is completed according to TLC (10h), add saturated sodium bicarbonate solution, separate the liquids, wash the organic phase with water, extract the aqueous phase with CH2Cl2, combine the organic phases, add anhydrous Na2SO4 to dry the organic phase, filter, evaporate CH2Cl2, and obtain a mixture solid. Finally, separate and purify it by silica gel column chromatography (PE:EA=20:1) to obtain a red solid 6 with a yield of 83%.

[0127] mp118-120℃; 1 H NMR (500MHz, DMSO-d6) δ10.03 (s, 1H), 8.02 (d, J = 8.5Hz, 2H), 7.49 (d, J = 8.4Hz, 2H), 4.96 (s, 2H), 4.66 (s, 2H), 4.38 (s, 5H); 13 C NMR (126MHz, DMSO-d6) δ192.55, 169.78, 155.65, 134.25, 131.64, 123.36, 72.89, 70.86, 70.42, 69.32; HRMS (ESI) m / z calcd for C 18 H 14 FeO3[M+H] + :334.0292, found:334.0298.

[0128] Example 20: Synthesis of (E)-4-(3,5-dimethoxyphenylvinyl)phenyl ferrocenecarboxylate

[0129]

[0130] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and 3,5-dimethoxybenzaldehyde (0.25g, 0.0015mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=80:1) to obtain a red solid 2a with a yield of 28%.

[0131] mp130-134℃; 1 H NMR(500MHz,DMSO-d6)δ 7.68(d,J=8.2Hz,2H), 7.32(d,J=16.3Hz,1H), 7.24(d,J=8.2Hz,2H), 7.19(d,J=16.4H z, 1H), 6.80 (s, 2H), 6.43 (s, 1H), 4.93 (s, 2H), 4.63 (s, 2H), 4.37 (s, 5H), 3.79 (s, 6H); 13 C NMR (126MHz, DMSO-d6) δ170.13, 161.16, 150.48, 139.51, 135.06, 129.94, 129.03, 128.54, 128.00, 122.76, 104.98, 100.44, 72.63, 70.75, 70.34, 69.89, 67.60, 55.70; HRMS (ESI) m / z calcd for C 27 H 24 FeO4[M+H] + :468.1024, found:468.1025.

[0132] Example 21: Synthesis of (E)-4-(3,4-dimethoxyphenylvinyl)phenylferrocenecarboxylate

[0133]

[0134] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and 3,4-dimethoxybenzaldehyde (0.25g, 0.0015mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=80:1) to obtain a red solid 2b with a yield of 26%.

[0135] mp127-130℃; 1 H NMR (500MHz, DMSO-d6) δ7.65 (d, J=8.7Hz, 2H), 7.27 (d, J=2.0Hz, 1H), 7.23 (d, J=8.6Hz, 2H), 7.19 (s, 2H), 7.12 (dd, J=8 .3, 2.0Hz, 1H), 6.97 (d, J=8.3Hz, 1H), 4.94 (t, J=2.0Hz, 2H), 4.66-4.61 (m, 2H), 4.38 (s, 5H), 3.84 (s, 3H), 3.79 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ170.16, 150.07, 149.44, 149.27, 135.54, 130.42, 129.95, 129.02, 127.57, 12 5.86, 122.71, 120.48, 112.26, 109.69, 72.61, 70.75, 70.33, 69.93, 67.60, 55.99; HRMS(ESI)m / zcalcd for C 27 H 24 FeO4[M+H] + :468.1024, found: 468.1036.

[0136] Example 22: Synthesis of (E)-4-(3,4,5-trimethoxyphenylvinyl)phenyl ferrocenecarboxylate

[0137]

[0138] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and 3,4,5-trimethoxybenzaldehyde (0.3g, 0.0015mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=70:1) to obtain a red solid 2c with a yield of 34%.

[0139] mp165-168℃; 1 H NMR (500MHz, DMSO-d6) δ7.67 (d, J = 8.6Hz, 2H), 7.28 (d, J = 16.4Hz, 1H), 7.25 (d, J = 8.6Hz, 2H), 7.19 (d, J = 16. 4Hz, 1H), 6.95 (s, 2H), 4.94 (t, J = 2.0Hz, 2H), 4.64 (t, J = 2.0Hz, 2H), 4.38 (s, 5H), 3.85 (s, 6H), 3.69 (s, 3H); 13 C NMR (126MHz, DMSO-d6) δ170.15, 153.55, 150.29, 137.85, 135.27, 133.19, 129.95, 129.15, 127.77, 127.38, 122.78, 104.41, 72.63, 70.75, 70.34, 67.61, 60.56, 56.37; HRMS (ESI) m / z calcdfor C 28 H 26 FeO5[M+H] + :498.1130, found:498.1158.

[0140] Example 23: Synthesis of (E)-4-(2,4,5-trimethoxyphenylvinyl)phenylferrocenecarboxylate

[0141]

[0142] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and 2,4,5-trimethoxybenzaldehyde (0.3g, 0.0015mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=60:1) to obtain a red solid 2d with a yield of 37%.

[0143] mp145-147℃; 1 H NMR (500MHz, DMSO-d6) δ7.61 (d, J=8.2Hz, 2H), 7.35 (d, J=16.6Hz, 1H), 7.28 (s, 1H), 7.21 (d, J=8.2Hz, 2H) , 7.19(s, 1H), 6.72(s, 1H), 4.94(s, 2H), 4.63(s, 2H), 4.37(s, 5H), 3.86(s, 3H), 3.83(s, 3H), 3.80(s, 3H); 13 C NMR (126MHz, DMSO-d6) δ170.16, 151.94, 150.26, 149.95, 143.54, 135.99, 129.94, 127.41, 125.89, 123.1 6, 122.72, 117.38, 110.49, 98.70, 72.61, 70.74, 70.32, 69.94, 67.60, 56.89, 56.76, 56.24; HRMS (ESI) m / z calcd for C 28 H 26 FeO5[M+H] + :498.1130, found:498.1135.

[0144] Example 24: Synthesis of (E)-4-(4-fluorophenylvinyl)phenyl ferrocenecarboxylate

[0145]

[0146] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and p-fluorobenzaldehyde (0.19g, 0.0015mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=80:1) to obtain a red solid 2e with a yield of 34%.

[0147] mp164-168℃; 1 H NMR (500MHz, DMSO-d6) δ7.68 (d, J=5.5Hz, 2H), 7.67 (d, J=5.3Hz, 2H), 7.27 (s, 2H), 7.24 (dd , J=8.7, 2.1Hz, 3H), 7.22 (s, 1H), 4.94 (t, J=2.0Hz, 2H), 4.63 (t, J=2.0Hz, 2H), 4.38 (s, 5H); 13 C NMR (126MHz, DMSO-d6) δ170.14, 163.12, 161.17, 150.43, 135.10, 134.10, 128.87, 1 28.80, 127.93, 127.82, 122.76, 116.15, 115.98, 72.63, 70.75, 70.34; HRMS (ESI) m / z calcd for C 29 H 15 FFeO2[M+H] + :426.0719, found:426.0714.

[0148] Example 25: Synthesis of (E)-4-(4-chlorophenylvinyl)phenylferrocenecarboxylate

[0149]

[0150] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and p-chlorobenzaldehyde (0.21g, 0.0015mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a solid mixture, and finally silica gel column chromatography (PE:EA=80:1) was used for separation and purification to obtain a red solid 2f with a yield of 32%.

[0151] mp175-177℃; 1 H NMR (500MHz, DMSO-d6) δ7.72-7.68 (m, 2H), 7.68-7.63 (m, 2H), 7.48-7.43 (m, 2H), 7.34 (d, J = 16.5Hz, 1H) , 7.27 (d, J = 9.8Hz, 2H), 7.25 (d, J = 2.0Hz, 1H), 4.94 (t, J = 2.0Hz, 2H), 4.63 (t, J = 1.9Hz, 2H), 4.38 (s, 5H); 13 C NMR (126MHz, DMSO-d6) δ170.13, 150.59, 136.48, 134.92, 132.41, 129.19, 1 28.92, 128.62, 128.09, 127.66, 122.80, 72.65, 70.76, 70.35; HRMS (ESI) m / z calcd for C 29 H 15 ClFeO2[M+H] + :442.0423, found:442.0422.

[0152] Example 26: Synthesis of (E)-4-(4-bromostyryl)phenylferrocenecarboxylate

[0153]

[0154] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and p-bromobenzaldehyde (0.28g, 0.0015mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1 M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=80:1) to obtain 2 g of red solid with a yield of 33%.

[0155] mp184-186℃; 1 H NMR (500MHz, DMSO-d6) δ7.72-7.68 (m, 2H), 7.59 (s, 4H), 7.36 (d, J = 16.4Hz, 1H), 7.26 (dd, J = 5. 6, 3.6Hz, 2H), 7.24 (d, J = 5.3Hz, 1H), 4.94 (t, J = 2.0Hz, 2H), 4.63 (t, J = 2.0Hz, 2H), 4.38 (s, 5H); 13 C NMR (126MHz, DMSO-d6) δ170.11, 150.61, 136.81, 134.90, 132.08, 128.98, 1 28.92, 128.10, 127.72, 122.80, 121.00, 72.64, 70.75, 70.34; HRMS (ESI) m / z calcd for C 29 H 15 BrFeO2[M+H] + :485.9918, found:485.9908.

[0156] Example 27: Synthesis of (E) 4-(3,5-dimethylphenylvinyl)phenyl ferrocenecarboxylate

[0157]

[0158] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place it under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and 3,5-dimethylbenzaldehyde (0.2g, 0.0015mol), and continue to heat and reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally silica gel column chromatography (PE:EA=100:1) was used for separation and purification to obtain a red solid 2h with a yield of 38%.

[0159] mp137-139℃; 1 H NMR (500MHz, DMSO-d6) δ7.70-7.65 (m, 2H), 7.24 (d, J=3.3Hz, 2H), 7.23 (d, J=1.7Hz, 2H), 7.22 (s, 1H), 7.1 7(d,J=16.4Hz,1H), 6.93(s,1H), 4.94(t,J=2.0Hz,2H), 4.63(t,J=2.0Hz,2H), 4.37(s,5H), 2.30(s,6H); 13 C NMR (126MHz, DMSO-d6) δ170.14, 150.35, 138.08, 137.30, 135.26, 129.73, 1 29.11, 127.87, 127.62, 124.82, 122.75, 72.63, 70.76, 70.34; HRMS (ESI) m / z calcd 1or C 27 H 24 FeO2[M+H] + :436.1126, found:436.1126.

[0160] Example 28: Synthesis of (E)-4-(4-isopropylphenylvinyl)phenylferrocenecarboxylate

[0161]

[0162] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and cuminaldehyde (0.22g, 0.0015mol), and continue to heat under reflux at 66°C. After the reaction was completed as judged by TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquids were separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquids were separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, and CH2Cl2 was evaporated to obtain a solid mixture, and finally separated and purified by silica gel column chromatography (PE:EA=100:1) to obtain a red solid 2i with a yield of 31%.

[0163] mp160-161℃; 1 H NMR (500MHz, Chloroform-d) δ7.60-7.55 (m, 2H), 7.51-7.46 (m, 2H), 7.26 (d, J = 7.9Hz, 2H), 7.23-7.17 (m, 2H), 7.10 (s, 2H), 5.00 (t, J = 2.0Hz, 2H), 4.53 (t, J = 2.0Hz, 2H), 4.34 (s, 5H), 2.95 (hept, J = 6.9Hz, 1H), 1.30 (d, J = 6.9Hz, 6H); 13 CNMR (126MHz, DMSO-d6) δ170.15, 150.29, 148.54, 135.30, 135.11, 128.90, 127 .82, 127.12, 126.98, 122.73, 72.63, 70.75, 70.34, 33.67, 24.27; HRMS (ESI) m / z calcd for C 28 H 26 FeO2[M+H] + :450.1282, found:450.1287.

[0164] Example 29: Synthesis of (E)-4-(4-tert-butylphenylvinyl)phenylferrocenecarboxylate

[0165]

[0166] Take a 250mL three-necked flask, add 1.6g (0.024mol) of zinc copper couple, under nitrogen protection, pump and inflate 3 times, inject 120mL of THF with a syringe, place the reaction system in an ice-water bath (0-5°C) and stir, then add 1.3mL (0.012mol) of titanium tetrachloride, after the addition is complete, place under reflux and stir at 66°C. After reacting for 2.5h, cool the reaction system in an ice-water bath (0-5°C), add a mixed THF solution of compound 6 (0.5g, 0.0015mol) and p-tert-butylbenzaldehyde (0.24g, 0.0015mol), and continue to heat under reflux at 66°C. After the reaction was completed according to TLC (6h), 1M hydrochloric acid solution was added to adjust the pH to weak acidity, the liquid was separated, the organic phase was washed with water, the aqueous phase was extracted with CH2Cl2, the organic phases were combined, saturated sodium bicarbonate solution was added to wash the organic phase, the liquid was separated, anhydrous Na2SO4 was added to dry the organic phase, filtered, CH2Cl2 was evaporated to obtain a mixture solid, and finally separated and purified by silica gel column chromatography (PE:EA=100:1) to obtain a red solid 2j with a yield of 29%. -

[0167] mp179-181℃; 1 H NMR(500MHz,Chloroform-d)δ7.59-7.52(m,2H),7.50-7.44(m,2H),7.42-7.37(m,2H),7.21-7.14(m , 2H), 7.08 (d, J = 1.2Hz, 2H), 4.97 (t, J = 2.0Hz, 2H), 4.51 (t, J = 2.0Hz, 2H), 4.31 (s, 5H), 1.34 (s, 9H); 13 C NMR (126MHz, DMSO-d6) δ150.76, 150.31, 135.29, 134.70, 128.79, 127.84, 127.20, 126.73, 125.95, 122.73, 72.63, 70.75, 70.34, 31.54; HRMS (ESI) m / z calcd for C 29 H 28 FeO2[M+H] + :464.1439, found: 464.1474.

Claims

1. A compound represented by the following formula (I) and (II) or a pharmaceutically acceptable salt thereof: The method for preparing compound (I) according to claim 1, characterized in that: A step selected from the following reaction scheme:

2. Reaction route 1: Ferrocenecarboxylic acid, oxalyl chloride, and N,N-dimethylformamide (DMF) are dissolved in dichloromethane, and an acylation reaction occurs under the protection of an inert gas, nitrogen, to obtain ferrocenecarboxylic acid chloride, wherein DMF is a catalyst, dichloromethane is a solvent, the amount of ferrocenecarboxylic acid is 1.0 molar equivalent, the amount of oxalyl chloride is 2.0 molar equivalent, the amount of DMF is 0.05 molar equivalent, the reaction concentration is 0.05M, the reaction temperature is room temperature, and the reaction time is 4-6h.

3. Reaction route 2: Ferrocenecarbonyl chloride, anisole / isophenylene dimethyl ether, and aluminum chloride undergo Friedel-Crafts acylation under the protection of inert gas nitrogen to obtain intermediate products 3 and 4, wherein: Aluminum chloride is used as a catalyst, dichloromethane is used as a solvent, the amount of ferrocenecarbonyl chloride is 1.0 molar equivalent, the amount of anisole / isophenylene dimethyl ether is 1.0 molar equivalent, the amount of aluminum chloride is 1.2 molar equivalent, and the reaction concentration is 0.05 M. The temperature during the feeding process is 0-5°C (ice water bath), the reaction temperature is room temperature, and the reaction time is 8 hours.

4. Reaction route 3: Compound 3 and boron tribromide undergo demethylation reaction under the protection of inert gas nitrogen to obtain intermediate product 5, wherein: Boron tribromide was used as a catalyst, dichloromethane was used as a solvent, the amount of compound 3 was 1.0 molar equivalent, the amount of boron tribromide was 6.0 molar equivalent, the reaction concentration was 0.05M, the temperature during the catalyst addition process was -78°C, the reaction temperature was room temperature, and the reaction time was 2h.

5. Reaction route 4: Compounds 3, 4, 5, substituted benzaldehydes (3,5-dimethoxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 2,4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 2,4,5-trimethoxybenzaldehyde, 2,3,4-trimethoxybenzaldehyde, 2,4,6-trimethoxybenzaldehyde), titanium tetrachloride, zinc copper couple, tetrahydrofuran, under the protection of inert gas nitrogen, undergo McMurray coupling reaction to obtain type (I) products 1a-1n, wherein, Titanium tetrachloride and zinc copper couple are used as catalysts, tetrahydrofuran is used as solvent, the amount of compounds 3, 4, and 5 is 1.0 molar equivalent, the amount of substituted benzaldehyde is 1.1 molar equivalent, the amount of titanium tetrachloride is 1.0 molar equivalent, the amount of zinc copper couple is 2.0 molar equivalent, the reaction concentration is 0.05M, the temperature during the catalyst addition process is 0-5°C (ice water bath), the reaction temperature is 66°C (heating reflux), and the reaction time is 10h. The method for preparing compound (II) according to claim 1, characterized in that: A step selected from the following reaction scheme:

6. Reaction route 1: Ferrocenecarboxylic acid, p-hydroxybenzaldehyde, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI), and 4-dimethylaminopyridine (DMAP) undergo esterification reaction under the protection of inert gas nitrogen to obtain intermediate product 6, wherein EDC·HCl and DMAP are catalysts, dichloromethane is solvent, the amount of ferrocenecarboxylic acid is 1.0 molar equivalent, the amount of p-hydroxybenzaldehyde is 1.0 molar equivalent, the amount of EDCI is 1.5 molar equivalent, the amount of DMAP is 0.1 molar equivalent, the reaction concentration is 0.05M, the temperature during the catalyst addition process is 0-5°C (ice water bath), the reaction temperature is room temperature, and the reaction time is 10h.

7. Reaction route 2: Compound 6, substituted benzaldehyde (3,5-dimethoxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 2,4,5-trimethoxybenzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, 3,5-dimethylbenzaldehyde, p-isopropylbenzaldehyde, p-tert-butylbenzaldehyde), titanium tetrachloride, zinc copper couple, tetrahydrofuran, under the protection of inert gas nitrogen, undergo McMurray coupling reaction to obtain type (II) products 2a-2j, wherein, Titanium tetrachloride and zinc-copper couple are used as catalysts, tetrahydrofuran is used as solvent, the amount of compound 6 is 1.0 molar equivalent, the amount of substituted benzaldehyde is 1.1 molar equivalent, the amount of titanium tetrachloride is 1.0 molar equivalent, the amount of zinc-copper couple is 2.0 molar equivalent, the reaction concentration is 0.05M, the temperature during the catalyst addition process is 0-5°C (ice-water bath), the reaction temperature is 66°C (heating to reflux), and the reaction time is 10h.

Images