A process for the preparation of (z)-1-aryl sulfide-2-phenol ether-4-aryl-trisubstituted-1-buten-3-ynes

Abstract

The application discloses a synthesis method of a (Z)-1-aryl sulfide-2-phenol ether-4-aryl-trisubstituted-1-butene-3-alkyne compound, which comprises two-step room temperature reactions: firstly, in a dry reaction container, 1,3-di-alkynyl triiodide reagent (I), a phenol compound, a base reagent and an organic solvent are mixed, and stirring reaction is carried out at room temperature until the starting material is completely consumed, and the solvent is removed by concentration under reduced pressure; then, a sulfenol compound, a copper catalyst and an organic solvent are added into the concentrated residue, and stirring reaction is carried out at room temperature until completion, and the target product (II) is obtained through post-treatment. The molar ratio of the 1,3-di-alkynyl triiodide reagent (I), the phenol compound and the sulfenol compound is 1:1.05:(1.1-1.3); the copper catalyst is selected from one of cuprous iodide, cuprous chloride and tetraethylammonium copper tetrafluoroborate, and the copper catalyst is preferably tetraethylammonium copper tetrafluoroborate; and the organic solvent is selected from acetonitrile, 1,2-dichloroethane and the like, and the total amount of the organic solvent added is 0.1 mmol in terms of the amount of substance of the reagent shown in formula (I). The method has mild reaction conditions, simple operation and can efficiently prepare the target compound.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceutical intermediates and organic synthesis technology, specifically to a method for preparing (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds. Background Technology

[0002] In 1-butene-3-yne compounds, the carbon-carbon double and triple bonds are conjugated, forming a unique π-π conjugated system. This system not only possesses excellent electron transfer properties but can also construct complex organic molecular skeletons through addition and cyclization reactions. The molecular structure of (Z)-1-aryl thioether-2-phenolic ether-4-aryl-trisubstituted-1-butene-3-yne derivatives contains two key heteroatom functional groups: aryl thioether and phenolic ether. The sulfur atom in the aryl thioether exhibits strong nucleophilicity and coordination ability, participating in various metal-catalyzed reactions, while its electronic effects can regulate the electron cloud density of the conjugated system. The oxygen atom in the phenolic ether imparts certain polarity, biocompatibility, and photophysical properties to the molecule, and the ether bond structure provides good chemical stability. Furthermore, the Z-configuration of the double bonds in the molecule exhibits stereospecificity, effectively controlling the spatial structure and packing mode of the molecule, further expanding its application scenarios. In the field of organic synthesis, it can serve as a key intermediate for the efficient construction of complex heterocyclic compounds and natural products (Yang L, et al. [J] Chemistry Select 2019, 4(2), 311–315; Tang Meizhong, et al. [J] The Journal of Organic Chemistry, 88.21(2023):15466-15472.); in the field of medicinal chemistry, it can serve as a lead compound for the development of novel antitumor, antibacterial, and anti-inflammatory drugs (Ryu CK, et al. [J] European Journal of Medicinal Chemistry 40 (2005) 438–444; Dutta, N. B, et al., [J] Front. Chem. 2022, 10, 1089860.); in the field of materials science, it can be used to prepare organic optoelectronic materials, polymer materials, sensor materials, etc. (Naito T, et al., [J] ChemRxiv 2025.

[0003] The synthesis of (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-buten-3-yne with a conjugated enyne (1-buten-3-yne) as its core skeleton is challenging due to the precise construction of the C1-aryl thioether (ArS-), C2-aryl ether (ArO-), and C4-aryl groups, with the double bonds in a Z configuration. Currently, there are no reported synthetic methods for the target compound; only a few reports of synthesizing similar structures exist. (i) Regio / stereoselective hydrosulfideation of 1,3-butadiyne; Venkateswarlu C. et al. reported a stereospecific cis hydrosulfideation reaction of 1,3-butadiyne, yielding (Z)-1-(thioether)-1-buten-3-yne derivatives by aryl sulfideation at the C1 position (Cheerladinne V, et al., [J]ChemInform 2015, 46(23); Renata, G; et al., [J]J. Braz. Chem. Soc. 2016, 27(5), 987–994.). Its limitation is the inability to simultaneously functionalize at both the C1 and C2 positions. (ii) Cross-coupling of prefunctionalized alkenyl halogen / tin reagents with aryl alkynes: Cai MZ. et al. reported the synthesis of (Z)-2-aryl thioether-substituted 1-buten-3-yne, using (Z)-1-arylthio-2-halogen / tin-vinyl intermediate, and then aryl acetylene via Pd / Cu co-catalytic coupling (Sonogashira / Stille) to construct a C3-C4 alkyne bond in one step while retaining the Z-configuration (Cai M.-Z, et al., [J]Synth. Commun. 2006, 36(13), 1849–1858.). The drawback is that it requires the use of expensive intermediates. (iii) Nucleophilic addition-elimination of acetylenes / enynylenes: Cheng-Pan Zhang reported the synthesis of (Z)-1,2-diarylthioether-1-aryl olefins by using 4-aryl-1,3-buten-2-one (acetylenes) as a substrate and introducing thioether and ether bonds simultaneously / stepwise at the C1 / C2 positions through nucleophilic addition-elimination of arylthiophenols / phenols, and achieving Z-selectivity through base regulation (Zhang C.-P, et al., [J]ChemistrySelect 2019, 4(12), 3564–3568.). Its shortcoming is that it is not possible to introduce thioether and ether bonds simultaneously / stepwise at the C1 / C2 positions.

[0004] Based on the above analysis, there is an urgent need in this field for a synthetic method that simultaneously introduces thioether and phenolic ether bonds into the C1 and C2 of 1-buten-3-yne. Summary of the Invention

[0005] To address the aforementioned deficiencies, this application provides a simple and mild method for synthesizing (Z)-1-p-tolyl thioether-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne compounds.

[0006] The technical solution of this application discloses a method for preparing (Z)-1-arylsulfide-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds, comprising the following steps:

[0007] S1. 1,3-Dyneyltrivalent iodine reagent, phenolic compound, base reagent, and organic solvent are stirred at room temperature to allow a nucleophilic addition reaction to occur. After the reaction is complete, the solvent is removed by vacuum distillation to obtain a concentrated residue.

[0008] S2. Thiophenolic compounds, copper catalysts, and organic solvents were added to the concentrated residue species. The mixture was stirred at room temperature to 40°C to allow for nucleophilic substitution. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the concentrated residue. The (Z)-1-aryl thioether-2-phenolic ether-4-aryl-trisubstituted-1-butene-3-yne compounds were obtained by column chromatography.

[0009] The 1,3-diynyl trivalent iodine reagent has the following structural formula:

[0010] ;

[0011] In the formula, Ar 3 It can be any one of phenyl, heteroaryl, or naphthyl.

[0012] Furthermore, the molar ratio of the 1,3-diynyl trivalent iodine reagent, phenolic compounds, and thiophenolic compounds is 1:1.05:(1.1~1.3).

[0013] Furthermore, the alkaline reagent is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0014] Furthermore, the phenolic compound is selected from any one of phenol, p-methylphenol, o-methylphenol, p-methoxyphenol, p-nitrophenol, o-trifluoromethylphenol, m-methoxyphenol, p-chlorophenol, 2-bromo-4-methylphenol, 4-phenylphenol, 8-quinolinol, and estradiol.

[0015] Furthermore, the thiophenolic compound is selected from any one of p-methylthiophenol, p-ethylthiophenol, p-isopropylthiophenol, 2,6-dimethylthiophenol, p-methoxythiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, 3,5-di(trifluoromethyl)thiophenol, 2-naphthiophenol, and 2-methylfuranthiophenol.

[0016] Furthermore, the copper catalyst is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0017] Furthermore, the organic solvents mentioned in S1 and S2 are selected from any one of acetonitrile, 1,2-dichloroethane, tetrahydrofuran, N,N-dimethylformamide, and dichloromethane.

[0018] Furthermore, after the S2 reaction is completed, a purification step is also included for (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds.

[0019] Furthermore, the purification specifically involves: extracting, drying, vacuum distilling, and separating and purifying the reaction system after the S2 reaction is completed.

[0020] Beneficial effects:

[0021] 1. This application uses 1,3-diynyl trivalent iodine reagent as a starting material and applies it to the synthesis of this type of Z-configuration compound for the first time, filling the gap in the prior art. By utilizing the unique electrophilic activity of this reagent, the one-step construction of phenolic ether bonds, thioether bonds and aryl introduction can be achieved, simplifying the reaction steps and improving the reaction efficiency.

[0022] 2. The reaction conditions of this application are mild (room temperature, 25°C), requiring no high temperature or high pressure, no precious metal catalysts, only inexpensive copper reagents for catalysis, resulting in low production costs, environmental friendliness, and conformity with the trend of green chemistry development.

[0023] 3. It can efficiently synthesize target compounds with 25 different substituents in Ar... 1 Ar 2 Ar 3 The rings include various substitution types such as alkyl, alkoxy, halogen, and nitro, which can meet the needs of different fields such as heterocyclic synthesis, drug development, and functional material preparation.

[0024] 4. High product configuration selectivity, with Z-configuration selectivity ≥95%, no obvious E-configuration isomerization products, and high product purity. High reaction yield, with target product yield reaching 75%~95%, far exceeding existing classical methods (45%~60%).

[0025] 5. It is easy to operate, has few reaction steps, simple post-processing, and does not require complex separation equipment. It can realize small-batch preparation in the laboratory and has the potential for large-scale industrial application.

[0026] 6. The target product retains multiple active sites such as Z-carbon-carbon double bonds, thioether bonds, phenolic ether bonds, and carbon-carbon triple bonds, which can be further used for heterocyclic synthesis, late-stage modification of drug molecules, and preparation of functional materials, showing broad application prospects. Attached Figure Description

[0027] Figure 1 This is a reaction diagram for the preparation of the compound in Example 1 of the present invention.

[0028] Figure 2 This is a reaction diagram of the preparation of the compound in Example 2 of the present invention.

[0029] Figure 3 This is a reaction diagram of the preparation of the compound in Example 4 of the present invention.

[0030] Figure 4 This is a reaction diagram of the preparation of the compound in Example 4 of the present invention.

[0031] Figure 5 This is a reaction diagram for the preparation of the compound in Example 5 of the present invention.

[0032] Figure 6 This is a reaction diagram for the preparation of the compound in Example 6 of the present invention.

[0033] Figure 7 This is a reaction diagram of the preparation of the compound in Example 7 of the present invention.

[0034] Figure 8 This is a reaction diagram of the preparation of compound 8 in Example 8 of the present invention.

[0035] Figure 9 This is a reaction diagram for the preparation of compound 9 in Example 9 of the present invention.

[0036] Figure 10 This is a reaction diagram of the preparation of compound 10 in Example 10 of the present invention.

[0037] Figure 11 This is a reaction diagram of the preparation of compound 11 in Example 1 of the present invention.

[0038] Figure 12 This is a reaction diagram of the preparation of compound 12 in Example 1 of the present invention.

[0039] Figure 13 This is a reaction diagram of the preparation of compound 13 in Example 1 of the present invention.

[0040] Figure 14 This is a reaction diagram of the preparation of compound 14 in Example 1 of the present invention.

[0041] Figure 15 This is a reaction diagram of the preparation of compound 15 in Example 1 of the present invention.

[0042] Figure 16 This is a reaction diagram of the preparation of compound 16 in Example 1 of the present invention.

[0043] Figure 17This is a reaction diagram of the preparation of compound 17 in Example 1 of the present invention.

[0044] Figure 18 This is a reaction diagram of the preparation of compound 18 in Example 18 of the present invention.

[0045] Figure 19 This is a reaction diagram of the preparation of compound 19 in Example 19 of the present invention.

[0046] Figure 20 This is a reaction diagram of the preparation of compound 20 in Example 20 of the present invention.

[0047] Figure 21 This is a reaction diagram of the preparation of the compound in Example 21 of the present invention.

[0048] Figure 22 This is a reaction diagram of the preparation of the compound in Example 22 of the present invention.

[0049] Figure 23 This is a reaction diagram of the preparation of compound 23 in Example 23 of the present invention.

[0050] Figure 24 This is a reaction diagram of the preparation of compound 24 in Example 24 of the present invention.

[0051] Figure 25 This is a reaction diagram of the preparation of compound 25 in Example 25 of the present invention.

[0052] Figure 26 This is a general formula diagram of the preparation method of the present invention. Detailed Implementation

[0053] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0054] The first embodiment of this application discloses a method for preparing (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds, comprising the following steps:

[0055] S1. 1,3-Dyneyltrivalent iodine reagent, phenolic compound, base reagent, and organic solvent are stirred at room temperature to allow a nucleophilic addition reaction to occur. After the reaction is complete, the solvent is removed by vacuum distillation to obtain a concentrated residue.

[0056] S2. Thiophenolic compounds, copper catalysts, and organic solvents were added to the concentrated residue. The mixture was stirred at room temperature to 40°C to induce a nucleophilic substitution reaction. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the concentrated residue. The (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds were obtained by column chromatography.

[0057] In this embodiment, the chemical structure of the 1,3-diynyl trivalent iodine reagent is shown in Formula I:

[0058] ;

[0059] In the formula, Ar 3 It is any one of phenyl, heteroaryl, and naphthyl;

[0060] It should be noted that this reagent can be prepared by oneself according to the methods disclosed in existing literature, and can specifically be 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 4-p-methylphenyl-1,3-butadiynyl trivalent iodine reagent, 4-o-chlorophenyl-1,3-butadiynyl trivalent iodine reagent, 4-(1-naphthylphenyl)-1,3-butadiynyl trivalent iodine reagent, 4-thiophene-1,3-butadiynyl trivalent iodine reagent, etc.

[0061] This reagent possesses unique electrophilic activity, enabling one-step construction of phenolic ether bonds, thioether bonds, and aryl group introduction, simplifying the reaction steps and improving reaction efficiency. This reagent can be prepared independently according to methods disclosed in existing literature.

[0062] The phenolic compounds are aromatic compounds containing phenol, p-methylphenol, o-methylphenol, p-methoxyphenol, p-nitrophenol, o-trifluoromethylphenol, m-methoxyphenol, p-chlorophenol, 2-bromo-4-methylphenol, 4-phenylphenol, 8-quinolinol, and estradiol groups, all containing Ar. 1 -OH group (where Ar) 1 (Aryl), which reacts with 1,3-diynyl trivalent iodine reagents via an S1 reaction to convert Ar 1 The O-structure is introduced into the 2-position 1-butene-3-yne structure;

[0063] The thiophenolic compounds are those containing p-methylthiophenol, p-ethylthiophenol, p-isopropylthiophenol, 2,6-dimethylthiophenol, p-methoxythiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, 3,5-di(trifluoromethyl)thiophenol, 2-naphthiophenol, and 2-methylfuranthiophenol groups, all containing Ar. 2 The SH group, in the S2 reaction, can convert Ar... 2 The S-group is cis-introduced into the 1-site of 1-buten-3-yne.

[0064] like Figure 26(The general formula for the preparation of the target compound in this application) is shown, wherein (II) is the (Z)-1-arylthioether-2-phenol ether-4-aryl-trisubstituted-1-buten-3-yne compound obtained by the reaction in this application. It can be seen that the 1,3-diynyl trivalent iodine reagent (I) introduces the Ar group of the phenolic compound at the 2 position through the nucleophilic addition reaction described in S1. 1 The O- group was then introduced at the 1-position via the nucleophilic substitution reaction described in S2, resulting in the introduction of an Ar group from a thiophenolic compound. 2 S-groups. This allows for the simultaneous introduction of (Z)-1-arylthioether-2-phenolic ether groups, resulting in the retention of multiple active sites on the target product (II), including Z-carbon double bonds, thioether bonds, phenolic ether bonds, and carbon-carbon triple bonds. This enables further applications in heterocyclic synthesis, late-stage drug molecule modification, and functional material preparation, showing broad application prospects. Furthermore, Ar... 1 Ar 2 Ar 3 The rings include various substitution types such as alkyl, alkoxy, halogen, and nitro, which can meet the needs of different fields such as heterocyclic synthesis, drug development, and functional material preparation.

[0065] In the above reaction process, reaction S1 continues until the 1,3-diynyltrivalent iodine reagent is completely consumed, and reaction S2 continues until the reaction product is completely generated. The reaction progress of both reactions can be monitored by thin-layer chromatography (TLC). The molar ratio of the 1,3-diynyltrivalent iodine reagent, phenolic compounds, and thiophenolic compounds is 1:1.05:(1.1~1.3).

[0066] In a specific embodiment, the alkaline reagent is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene; preferably cesium carbonate.

[0067] The copper catalyst is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene; preferably copper tetrafluoroborate tetraacetonitrile.

[0068] The organic solvents mentioned in S1 and S2 are selected from any one of acetonitrile, 1,2-dichloroethane, tetrahydrofuran, N,N-dimethylformamide, and dichloromethane; preferably acetonitrile and 1,2-dichloroethane. The total amount of the organic solvent added is 1 mL, which is 0.1 mmol based on the amount of 1,3-diynyl trivalent iodine reagent (I) shown in Formula 1.

[0069] After the S2 reaction is completed, the purification steps for (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds are also included, such as extraction, drying, vacuum distillation, column chromatography separation and purification.

[0070] The "room temperature" mentioned in reactions S1 and S2 of this application refers to 20-30°C.

[0071] The technical solution of this application will be described in detail below through specific embodiments.

[0072] In the following examples, cesium carbonate (Cs2CO3) was used as the base reagent; acetonitrile (MeCN) was used as the organic solvent in reaction S1; copper tetrafluoroborate copper tetraacetonitrile (Cu(CH3CN)4BF4) was used as the copper catalyst; and 1,2-dichloroethane (DCE) was used as the organic solvent in reaction S2. The reactions were carried out at room temperature to 40°C.

[0073] Example 1

[0074] Preparation of compound (Z)-1-p-tolyl thioether-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 1 As shown:

[0075] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 4 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography using petroleum ether as the eluent. The target fraction was collected and concentrated to give the target compound (Z)-1-p-tolylthioether-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, with a yield of 95%. Z-configuration selectivity: 97%.

[0076] The product test data are as follows:

[0077] R f = 0.60 (PE). 1H NMR (600 MHz, CDCl3) δ7.36 (q, J = 7.86 Hz, 5H), 7.25 (s, 5H), 7.15 (d, J = 4.02 Hz, 3H), 7.10 (t, J = 7.44 Hz, 1H), 6.41 (s,1H), 2.35 (s, 3H), 13 C NMR (150 MHz, CDCl3) δ 155.65, 137.63, 131.92, 131.43131.07, 130.52, 130.09, 129.39, 128.71, 128.38, 123.27, 122.11, 121.37,117.87, 92.08, 83.48, 21.19. HRMS calcd for C 23 H 18 OS [M+H] + 342.1157, found: 342.1160.

[0078] Example 2

[0079] Preparation of compound (Z)-1-p-ethylphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 2 As shown:

[0080] 4-Phenylacetyltrivalent iodine reagent (0.10 mmol, 1.0 equivalent), phenol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. p-Ethiophene (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 5 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-ethylphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 88%.

[0081] The product test data are as follows:

[0082] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 7.92 Hz, 2H),7.34 (t, J = 7.56 Hz, 1H), 7.31 - 7.27 (m, 3H), 7.17 (q, J = 8.04 Hz, 4H),7.13 - 7.08 (m, 2H), 6.41 (s, 1H), 1.23 (dd, J = 13.38, 5.76Hz, 3H). 13 C NMR(150 MHz, CDCl3) δ 155.49, 144.00, 131.79, 131.41, 130.61, 129.60, 129.38,128.92, 128.85, 128.69, 128.36, 123.25, 122.11, 121.40, 119.53, 117.85,91.64, 83.46, 28.57, 15.61. HRMS calcd for C24H20OS [M+H] + 357.1313, found: 357.1316.

[0083] Example 3

[0084] The preparation of compound (Z)-1-p-isopropylphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, and the reaction diagram of the compound preparation are shown in the figure. Figure 3 As shown:

[0085] 4-Phenylacetyltrivalent iodide reagent (0.10 mmol, 1.0 equivalent), phenol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodide reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. p-Isopropylthiophenol (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 5 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-isopropylphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 87%.

[0086] The product test data are as follows:

[0087] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 8.46 Hz, 2H), 7.37 (s, 1H), 7.35 (t, J = 8.52 Hz, 4H), 7.29 - 7.26 (m 5H), 7.15 (d, J = 8.7Hz, 1H), 7.1-7.09 (m, 1H), 6.43 (s, 1H), 1.32 (s, 6H), 1.30 (s, 1H). 13 C NMR(150 MHz, CDCl3) δ 155.64, 150.88, 131.42, 131.11, 130.32, 129.56, 129.38,129.20, 129.07, 128.69, 128.37, 126.40, 123.25, 122.12, 121.36, 119.24,118.06, 117.86, 92.04, 83.48, 34.69, 31.34. HRMS calcd for C 25 H 22 OS [M+H] + 371.1470, found: 371.1472.

[0088] Example 4

[0089] Preparation of compound (Z)-1-(2,6-dimethylphenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 4 As shown:

[0090] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butyrynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butyrynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 2,6-dimethylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 6 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(2,6-dimethylphenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 86%.

[0091] The product test data are as follows:

[0092] R f = 0.65 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.42 (d, J = 7.86 Hz, 1H), 7.35 (t, J = 8.28 Hz, 2H), 7.31- 7.29 (m, 1H), 7.23 (s, 3H), 7.16 (d, J =8.46 Hz, 3H), 7.12 (d, J = 8.34 Hz, 2H), 7.09 - 7.04 (m, 1H), 5.99 (s, 1H), 2.53 (s, 6H). 13C NMR (150 MHz, CDCl3) δ 155.74, 142.77, 131.74, 131.33,129.37, 129.08, 128.57, 128.44, 128.37, 128.33, 123.23, 123.07, 122.94,117.64, 117.49, 98.24, 91.86, 83.44, 22.27. HRMS calcd for C 24 H 20 OS [M+H] + 357.1313, found: 357.1315.

[0093] Example 5

[0094] Preparation of compound (Z)-1-p-methoxyphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 5 As shown:

[0095] 4-Phenylacetyltrivalent iodine reagent (0.10 mmol, 1.0 equivalent), phenol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. p-Methoxythiophenol (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 6 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methoxyphenyl sulfide-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 85%.

[0096] The product test data are as follows:

[0097] R f = 0.60 (PE). 1H NMR (600 MHz, CDCl3) δ 7.35 (t, J = 7.38 Hz 3H), 7.20 (t, J = 7.92 Hz 3H), 7.15 (d, J = 7.98 Hz 2H), 7.10 - 7.04 (m, 4H), 6.99(s, 1H), 6.75 (d, J = 8.1 Hz 1H), 6.45 (s, 1H), 3.76 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 160.14, 155.59, 138.37, 135.94, 131.45, 130.17, 130.00, 129.39,128.79, 128.39, 123.37, 122.11, 119.67, 117.98, 115.26, 113.22 (d, J = 13.5Hz), 112.65, 92.34, 83.33, 55.39. HRMS calcd for C 23 H 18 O2S [M+H] + 359.1106, found: 359.1108.

[0098] Example 6

[0099] Preparation of compound (Z)-1-(4-fluorophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 6 As shown:

[0100] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butyrynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butyrynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 4-fluorothiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 5 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(4-fluorophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 88%.

[0101] The product test data are as follows:

[0102] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.45 (q, J = 5.34Hz, 2H),7.34 (t, J = 7.68Hz, 3H), 7.23 (d, J = 4.26Hz 3H), 7.14 (d, J = 8.1Hz 2H),7.12 - 7.09 (m, 2H), 7.05 (q, J = 6.72 Hz, 2H), 6.32 (s, 1H). 13 C NMR (150MHz, CDCl3) δ 163.28, 161.64, 155.53, 132.68, 132.62, 131.80, 131.43, 129.78,129.58, 129.39, 128.81, 128.38, 126.38, 123.53, 123.41, 121.94, 120.38,118.18, 117.96, 116.54, 116.40, 92.35, 83.17. HRMS calcd for C 22 H 15 FOS [M+H] + 347.0906, found: 347.0909.

[0103] Example 7

[0104] Preparation of compound (Z)-1-(4-chlorophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 7 As shown:

[0105] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 4-chlorothiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 6 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(4-chlorophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 86%.

[0106] The product test data are as follows:

[0107] R f = 0.65 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.38 (q, J = 8.34Hz 3H), 7.31 (d, J = 8.34Hz 3H), 7.26 (m, 3H), 7.16 (d, J = 7.98Hz 2H), 7.12 (t, J =7.38Hz 1H), 6.35 (s, 1H). 13 C NMR (150 MHz, CDCl3) δ 155.53, 133.41, 131.48,131.17, 139.47, 129.43, 128.91, 128.43, 123.54, 121.89, 118.70, 118.11,92.71, 83.15. HRMS calcd for C 22 H 15 ClOS [M+H]+ 363.0610, found: 363.0612.

[0108] Example 8

[0109] Preparation of compound (Z)-1-(4-bromophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 8 As shown:

[0110] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 4-bromothiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 6 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(4-bromophenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 85%.

[0111] The product test data are as follows:

[0112] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.27 (t, J = 12.36 2H), 7.27 - 7.23 (m, 4H), 7.17 (s, 5H), 7.05 (q, J = 12.18 Hz, 3H), 6.26 (s, 1H). 13 C NMR (150 MHz, CDCl3) δ 155.40, 133.45, 132.30, 131.75, 131.40, 131.23,130.14, 129.55, 129.34, 128.83, 128.34, 123.47, 118.37, 118.28, 118.03,92.66, 83.01. HRMS calcd for C22 H 15 BrOS [M+H] + 407.0105, found: 407.0107.

[0113] Example 9

[0114] Preparation of compound (Z)-1-(3,5-bis(trifluoromethyl)phenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 9 As shown:

[0115] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butyrynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butyrynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 3,5-bis(trifluoromethyl)benzylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 8 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(3,5-bis(trifluoromethyl)phenyl sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 83%.

[0116] The product test data are as follows:

[0117] R f = 0.65 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.83 (s, 2H), 7.72 (d, J =7.68, 1H), 7.36 (t, J = 8.04, Hz, 4H), 7.30 (t, J = 5.88 Hz, 2H), 7.14 (d, J= 8.52 Hz, 4H), 6.27 (s, 1H). 13C NMR (150 MHz, CDCl3) δ 155.19, 139.00,136.83, 132.65, 132.43, 131.89, 131.59, 129.44, 129.25, 128.46, 124.07,121.42, 120.41, 119.29, 118.85, 118.68, 112.76, 109.56, 94.03, 82.43. HRMScalcd for C 24 H 14 F6OS [M+H] + 465.0748, found: 465.0748.

[0118] Example 10

[0119] Preparation of compound (Z)-1-(2-naphthylbenzene sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 10 As shown:

[0120] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 2-naphthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 10 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(2-naphthylbenzene sulfide)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 80%.

[0121] The product test data are as follows:

[0122] R f = 0.60 (PE). 1H NMR (600 MHz, CDCl3) δ 7.92 (s, 1H), 7.82 - 7.78 (m, 3H), 7.53 - 7.46 (m, 3H), 7.36 (t, J = 7.68 Hz, 3H), 7.29 - 7.26 (m, 4H), 7.19 (d, J = 8.04 Hz, 2H), 7.12 (t, J = 7.2 Hz, 1H), 6.54 (s, 1H). 13 C NMR(150 MHz, CDCl3) δ 155.63, 133.78, 132.37, 132.08, 131.82, 131.47, 129.41,129.02, 128.81, 128.39, 127.87, 127.54, 127.44, 126.93, 126.35, 123.42,119.60, 118.06, 92.32, 83.10. HRMS calcd for C 26 H 18 OS [M+H] + 379.1157, found: 379.1159.

[0123] Example 11

[0124] Preparation of compound (Z)-1-(2-methylfuran-3-thioether)-2-phenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 11 As shown:

[0125] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of 2-methyl-3-mercaptofuran, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 12 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-(2-methylfuran-3-thioether)-2-phenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 81%.

[0126] The product test data are as follows:

[0127] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.34 (t, J = 7.5 Hz, 4H), 7.30 (s, 2H), 7.14 (d, J = 8.04 Hz, 3H), 7.09 t, J = 7.26Hz, 2H), 6.43 (s,1H), 6.13 (s, 1H), 2.35 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 155.61, 154.87,141.00, 131.74, 131.38, 129.50, 129.37, 128.67, 128.35, 123.20, 123.02,117.75, 114.61, 109.02, 91.94, 83.21, 11.96. HRMS calcd for C 21 H 16 O2S [M+H] + 333.0949, found: 333.0951.

[0128] Example 12

[0129] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-p-methylphenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 12 As shown:

[0130] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of p-methylphenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 5 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-p-methylphenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 90%.

[0131] The product test data are as follows:

[0132] R f = 0.6 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 7.98 Hz, 2H),7.31 - 7.26 (m, 6H), 7.16 (t, J = 7.86 Hz, 4H), 7.07 (d, J = 8.34 Hz, 2H), 6.39 (s, 1H), 2.36 (s, 3H), 2.34 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 153.55,137.55, 132.68, 132.31, 131.83, 131.46, 131.21, 130.46, 130.06, 129.86,129.45, 128.68, 128.38, 122.19, 120.85, 117.76, 92.02, 83.61, 21.20, 20.83.HRMS calcd for C 24 H 20OS [M+H] + 357.1313, found: 357.1315.

[0133] Example 13

[0134] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-o-methylphenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 13 As shown:

[0135] To a dry reaction tube, 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of o-methylphenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile were added sequentially. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane were added to the residue. The mixture was stirred at room temperature for another 5 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-o-methylphenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 93%.

[0136] The product test data are as follows:

[0137] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ7.38 (d, J = 7.86 Hz, 2H),7.32 - 7.28 (m, 1H), 7.25 (t J = 7.74 Hz, 3H), 7.20 (d, J = 8.34 Hz, 3H),7.18 (d, J = 6.3 Hz, 2H), 7.15 (d, J = 7.92 Hz, 1H), 7.06 (s, J =7.26 Hz, 1H), 6.34 (s, 1H), 2.39 (s, 3H), 2.36 (s, 3H). 13C NMR (150 MHz, CDCl3) δ154.00, 137.45, 133.04, 131.84, 131.37, 131.02, 130.35, 130.08, 129.98,128.65, 128.38, 126.63, 123.69, 122.15, 118.89, 118.12, 92.17, 83.49, 21.20,16.30. HRMS calcd for C 24 H 20 OS [M+H] + 357.1313, found: 357.1315.

[0138] Example 14

[0139] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-p-methoxyphenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 14 As shown:

[0140] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of p-methoxyphenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 5 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-p-methoxyphenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 90%.

[0141] The product test data are as follows:

[0142] R f = 0.60 (PE). 1H NMR (600 MHz, CDCl3) δ 7.36 (d, J = 7.92 Hz, 2H), 7.26 - 7.23 (m, 5H), 7.15 (d, J = 7.74 Hz, 2H), 7.09 (d, J = 8.88Hz, 2H), 6.87 (d, J = 8.94Hz, 2H), 6.30 (s, 1H), 3.79 (s, 3H), 2.34 (s, 3H). 13 C NMR(150 MHz, CDCl3) δ 155.82, 149.52, 137.49, 133.08, 131.38, 130.38, 130.06,128.67, 128.37, 122.13, 119.49, 119.40, 114.37, 92.40, 83.45, 55.76, 21.17.HRMS calcd for C 24 H 20 O2S [M+H] + 373.1262, found: 373.1265.

[0143] Example 15

[0144] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-p-nitrophenol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 15 As shown:

[0145] To a dry reaction tube, 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of p-nitrophenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile were added sequentially. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane were added to the residue. The mixture was stirred at room temperature for another 7 hours. After the reaction was confirmed to be complete by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-p-nitrophenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 88%.

[0146] The product test data are as follows:

[0147] R f = 0.3 (PE). 1 H NMR (600 MHz, CDCl3) δ 8.25 (d, J = 9.12 Hz, 2H), 7.34 (d, J = 7.98 Hz, 2H), 7.30 (d, J = 7.38 Hz, 3H), 7.27 (d, J = 6.66 Hz, 2H), 7.22 (d, J = 9.12 Hz, 2H), 7.16 (d, J = 7.92 Hz, 2H), 6.58 (s, 1H), 2.35(s, 3H). 13 C NMR (150 MHz, CDCl3) δ 160.57, 143.17, 138.30, 131.78, 131.50,130.91, 130.38, 130.25, 130.00, 129.71, 129.16, 128.52, 125.81, 125.37,121.55, 117.00, 92.56, 82.46, 21.20. HRMS calcd for C 23 H 17 NO3S [M+H] + 388.1007, found: 388.1010.

[0148] Example 16

[0149] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-(2-trifluoromethylphenol ether)-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula of the compound is shown in the figure. Figure 16 As shown:

[0150] 4-Phenylacetyltrivalent iodine reagent (0.10 mmol, 1.0 equivalent), 2-trifluoromethylphenol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. p-Methylthiophenol (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 7 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-(2-trifluoromethylphenol ether)-4-phenyl-trisubstituted-1-butene-3-yne with a product yield of 90%.

[0151] The product test data are as follows:

[0152] R f = 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.66 (d, J = 7.56 Hz, 1H), 7.53 (t, J = 7.83Hz, 1H), 7.37 (d, J = 7.98Hz, 2H), 7.30 - 7.26 (m, 6H), 7.16(d, J = 7.56 Hz, 3H), 6.51 (s, 1H), 2.35 (s, 1H). 13C NMR (150 MHz, CDCl3) δ153.40, 137.85, 132.94, 131.78, 131.44, 130.67, 130.14, 128.86, 128.42,127.12, 124.38, 123.36, 122.76, 121.92, 117.95, 92.35, 82.84, 21.18. HRMScalcd for C 24 H 17 F3OS [M+H] + 411.1030, found: 411.1030.

[0153] Example 17

[0154] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-(4-chlorophenol ether)-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 17 As shown:

[0155] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butyrynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of 4-chlorophenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butyrynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 6 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-(4-chlorophenol ether)-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 87%.

[0156] The product test data are as follows:

[0157] R f = 0.55 (PE). 1H NMR (600 MHz, CDCl3) δ 7.35 (d, J = 8.1 Hz, 2H),7.31 (s, 1H), 7.29 (s, 1H), 7.29 - 7.26 (m, 5H), 7.15 (d, J = 7.98 Hz, 2H),7.10 (s, 1H), 7.08 (s, 1H), 6.42 (s, 1H), 2.35 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 154.21, 137.82, 131.78, 131.44, 130.76, 130.62, 130.14, 129.80,129.36, 128.87, 128.44, 128.26, 122.20, 121.90, 119.07, 92.36, 83.04, 21.19.HRMS calcd for C 23 H 17 ClOS [M+H] + 377.0767, found: 377.0769.

[0158] Example 18

[0159] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-(2-bromo-4-methylphenol ether)-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 18 As shown:

[0160] 4-Phenylacetyltrivalent iodine reagent (0.10 mmol, 1.0 equivalent), 2-bromo-4-methylphenol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding a residue. p-Methylthiophenol (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 8 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-2-bromo-4-methylphenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 85%.

[0161] The product test data are as follows:

[0162] R f = 0.55 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 6.12 Hz, 1H),7.37 (d, J = 7.92 Hz, 2H), 7.30 (d, J = 7.8 Hz, 1H), 7.29 - 7.24 (m, 4H),7.15 (d, J = 7.92 Hz, 2H), 7.10 - 7.07 (m, 2H), 6.37 (s, 1H), 2.35 (s, 3H), 2.32 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 150.26, 137.57, 134.85, 133.73,132.52, 131.83, 131.39, 131.18, 130.45, 130.08, 129.48, 128.78 (J = 7.5 Hz),128.37, 122.04, 120.11, 119.41, 113.93, 92.62, 82.98, 21.19, 20.55. HRMScalcd for C 24 H 19 BrOS [M+H] +435.0418, found: 435.0420.

[0163] Example 19

[0164] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-(4-phenylphenol ether)-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 19 As shown:

[0165] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of 4-phenylphenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 7 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-4-phenylphenol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 88%.

[0166] The product test data are as follows:

[0167] R f = 0.65 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.59 (t, J = 5.76 Hz, 4H), 7.44 (t, J = 7.62 Hz, 2H), 7.39 (d, J = 8.04 Hz, 2H), 7.34 (t, J = 7.32 Hz,1H), 7.30 (t, J = 6.48 Hz, 2H), 7.28 - 7.24 (m, 5H), 7.18 (d, J = 7.98 Hz, 2H), 6.47 (s, 1H), 2.37 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.24, 140.80,137.70, 136.29, 131.74, 131.48, 131.01, 130.58, 130.14, 128.86 (J = 12.0 Hz), 128.42, 128.14, 127.05 (J = 3.0 Hz), 122.10, 121.87, 118.00, 92.19, 83.50,21.21. HRMS calcd for C 29 H 22 OS [M+H] + 419.1470, found: 419.1472.

[0168] Example 20

[0169] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-(8-quinolinol ether)-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 20 As shown:

[0170] Add 0.10 mmol (1.0 equivalent) of 4-phenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of 8-quinolinol, 0.10 mmol (1.05 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 10 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether:ethyl acetate = 100:1 as the eluent. The target fraction was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-(8-quinolinol ether)-4-phenyl-trisubstituted-1-buten-3-yne, with a product yield of 83%.

[0171] The product test data are as follows:

[0172] R f = 0.35 (EtOAc / PE = 1:10). 1H NMR (600 MHz, CDCl3) δ 9.01 (s, 1H),8.15 (d, J = 8.22 Hz, 1H), 7.52 (d, J = 7.92 Hz, 1H), 7.49 (t, J = 7.56 Hz,1H), 7.44 - 7.41 (m, 2H), 7.35 (d, J = 7.92 Hz, 2H), 7.24 - 7.19 (m, 5H), 7.12 (d, J = 7.68 Hz, 2H), 6.58 (s, 1H), 2.32 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 151.30, 150.02, 140.53, 137.56, 136.02, 131.91, 131.76, 131.43,131.13, 130.52, 130.05, 129.72, 128.64, 128.31, 126.45, 122.99, 122.32,122.12, 121.78, 113.99, 91.60, 83.63, 21.18. HRMS calcd for C 26 H 19 NOS [M+H] + 394.1266, found: 394.1268.

[0173] Example 21

[0174] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-estradiol ether-4-phenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 21 As shown:

[0175] 4-Phenylacetyltrivalent iodine reagent (0.10 mmol, 1.0 equivalent), estradiol (0.105 mmol, 1.05 equivalent), cesium carbonate (0.10 mmol, 1.0 equivalent), and acetonitrile (1 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 2 hours, and the reaction progress was monitored by thin-layer chromatography (TLC) until the 4-phenyl-1,3-butylacetyltrivalent iodine reagent was completely eliminated. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove the solvent acetonitrile, yielding the residue. p-Methylthiophenol (0.13 mmol, 1.3 equivalent), copper tetrafluoroborate tetraacetonitrile catalyst (0.01 mmol, 0.1 equivalent), and 1,2-dichloroethane (1 mL) were added to the residue. The mixture was stirred at room temperature for another 10 hours. After confirming the complete reaction by TLC, the solvent was evaporated under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-estradiol ether-4-phenyl-trisubstituted-1-butene-3-yne, with a product yield of 80%.

[0176] The product test data are as follows:

[0177] R f = 0.50 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.35 (d, J = 8.04 Hz, 2H), 7.30 - 7.26 (m, 3H), 7.14 (d, J = 7.98 Hz, 2H), 6.95 (dd, J = 8.46, 2.34 Hz, 1H), 6.89 (s, 1H), 6.41 (s, 1H), 2.92 (t, J = 4.92 Hz, 2H), 7.50 (q, J = 8.82Hz, 1H), 2.42 - 2.39 (m, 1H), 2.34 (s, 3H), 2.30 - 2.26 (m, 1H), 2.17 - 2.11(m, 1H), 2.07 - 2.05 (m, 1H), 2.03-1.99 (m, 1H), 1.96 (d, J = 12.24 Hz,1H), 1.66-1.58 (m, 3H), 1.55-1.48 (m, 4H), 1.47-1.42 (m, 2H), 0.92 (s,3H). 13C NMR (150 MHz, CDCl3) δ 221.04, 153.62, 137.85, 137.59, 134.54,131.83, 131.78, 131.50, 131.11, 130.47, 130.08, 130.00, 129.48, 128.70,128.37, 126.28, 122.24, 121.74, 117.54, 114.81, 91.77, 83.73, 50.55, 48.10,44.20, 38.32, 35.98, 31.69, 29.67, 26.60, 25.97, 21.70, 21.19, 13.97. HRMScalcd for C 35 H 34 O2S [M+H] + 519.2358, found: 519.2360.

[0178] Example 22

[0179] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-p-methylphenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 22 As shown:

[0180] Add 0.10 mmol (1.0 equivalent) of 4-p-methylphenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-p-methylphenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 8 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-p-methylphenyl-trisubstituted-1-butene-3-yne, with a product yield of 83%.

[0181] The product test data are as follows:

[0182] R f= 0.60 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.35 (q, J = 8.04 Hz, 5H),7.16 - 7.14 (m, 6H), 7.05 (d, J = 7.74 Hz, 2H), 6.38 (s, 1H), 2.35 (s, 3H),2.31 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 155.68, 138.99, 137.54, 132.14,131.36, 131.17, 130.44, 130.07, 129.36, 129.15, 123.20, 120.80, 119.01,117.85, 92.30, 82.86, 21.61, 21.18. HRMS calcd for C 24 H 20 OS [M+H] + 357.1313, found: 357.1315.

[0183] Example 23

[0184] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-o-chlorophenyl-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 23 As shown:

[0185] Add 0.10 mmol (1.0 equivalent) of 4-o-chlorophenyl-1,3-butadiynyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-o-chlorophenyl-1,3-butadiynyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 8 hours. After confirming the reaction is complete by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-o-chlorophenyl-trisubstituted-1-butene-3-yne, with a product yield of 81%.

[0186] The product test data are as follows:

[0187] R f = 0.55 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.27 (d, J = 8.04 Hz, 2H), 7.35 - 7.30 (m, 3H), 7.18 - 7.15 (m, 5H), 7.14 - 7.09 (m, 3H), 6.46 (s, 1H), 2.35 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 155.62, 137.78, 135.77, 133.03,131.54, 130.89, 130.70, 130.11, 129.61, 129.40, 129.43, 123.36, 122.45,118.07, 88.82, 88.34, 21.19. HRMS calcd for C 23 H 17 ClOS [M+H] + 377.0767, found: 377.0769.

[0188] Example 24

[0189] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-(1-naphthylphenyl)-trisubstituted-1-buten-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 24 As shown:

[0190] Add 0.10 mmol (1.0 equivalent) of 4-(1-naphthylphenyl)-1,3-butydinyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-(1-naphthylphenyl)-1,3-butydinyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 10 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-(1-naphthylphenyl)-trisubstituted-1-butene-3-yne with a product yield of 78%.

[0191] The product test data are as follows:

[0192] R f = 0.70 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.76 (t, J = 7.08 Hz, 2H),7.60 (d, J = 8.28 Hz, 1H), 7.50 (d, J = 7.08 Hz, 1H), 7.46 - 7.39 (m, 5H),7.36 - 7.33 (m, 2H), 7.26 (d, J = 8.04 Hz, 2H), 7.17 (d, J = 8.28 Hz, 3H), 6.48 (s, 1H), 2.36 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 155.77, 137.68, 133.07,132.93, 132.50, 131.13, 130.60, 130.21, 130.13, 129.53, 129.16, 128.25,126.88, 126.52, 126.01, 125.19, 123.64, 120.61, 119.75, 118.71, 90.78, 88.22,21.21. 27 H 20OS [M+H] + 393.1313, found: 393.1315.

[0193] Example 25

[0194] Preparation of compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-thiophene-trisubstituted-1-butene-3-yne, the reaction formula and preparation diagram of the compound are shown in the figure. Figure 25 As shown:

[0195] Add 0.10 mmol (1.0 equivalent) of 4-thiophene-1,3-butydinyl trivalent iodine reagent, 0.105 mmol (1.05 equivalent) of phenol, 0.10 mmol (1.0 equivalent) of cesium carbonate, and 1 mL of acetonitrile to a dry reaction tube in sequence. Stir the mixture at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography (TLC) until the 4-thiophene-1,3-butydinyl trivalent iodine reagent is completely eliminated. After the reaction is complete, concentrate the reaction solution under reduced pressure to remove the solvent acetonitrile, obtaining the residue. Add 0.13 mmol (1.3 equivalent) of p-methylthiophenol, 0.01 mmol (0.1 equivalent) of copper tetrafluoroborate tetraacetonitrile catalyst, and 1 mL of 1,2-dichloroethane to the residue. Continue stirring at room temperature for 12 hours. After confirming the complete reaction by TLC, evaporate the solvent under reduced pressure to obtain the crude product residue. The crude product residue was purified by silica gel column chromatography with petroleum ether as the eluent. The target component was collected and concentrated to obtain the target compound (Z)-1-p-methylphenyl sulfide-2-phenol ether-4-thiophene-trisubstituted-1-butene-3-yne, with a product yield of 76%.

[0196] The product test data are as follows:

[0197] R f = 0.45 (PE). 1 H NMR (600 MHz, CDCl3) δ 7.36 - 7.32 (m, 5H), 7.20 (q, J = 2.88 Hz, 1H), 7.14 (d, J = 6.36 Hz, 4H), 7.09 (t, J = 7.44 Hz, 1H), 6.95 (d, J = 5.34 Hz, 1H), 6.40 (s, 1H), 2.34 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.65, 137.61, 131.75, 131.05, 130.48, 130.09, 129.66, 129.40,129.3, 125.54, 123.19, 121.50, 121.15, 117.67, 87.16, 83.01, 21.19. HRMScalcd for C 21 H 16 OS2 [M+H] + 349.0721, found: 349.0724.

[0198] The above-described embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be included within the protection scope of the present invention.

Claims

1. A method for preparing a (Z)-1-arylsulfide-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compound, characterized in that, Includes the following steps: S1. 1,3-Dyneyltrivalent iodine reagent, phenolic compound, base reagent, and organic solvent are stirred at room temperature to allow a nucleophilic addition reaction to occur. After the reaction is complete, the solvent is removed by vacuum distillation to obtain a concentrated residue. S2. Thiophenolic compounds, copper catalysts, and organic solvents were added to the concentrated residue species. The mixture was stirred at room temperature to 40°C to allow for nucleophilic substitution. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the concentrated residue. The (Z)-1-aryl thioether-2-phenolic ether-4-aryl-trisubstituted-1-butene-3-yne compounds were obtained by column chromatography. The 1,3-diynyl trivalent iodine reagent has the following structural formula: ； In the formula, Ar 3 It can be any one of phenyl, heteroaryl, or naphthyl.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the 1,3-diynyl trivalent iodine reagent, phenolic compounds, and thiophenolic compounds is 1:1.05:(1.1-1.3).

3. The preparation method according to claim 1, characterized in that, The alkaline reagent is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

4. The preparation method according to claim 1, characterized in that, The phenolic compounds are selected from any one of phenol, p-methylphenol, o-methylphenol, p-methoxyphenol, p-nitrophenol, o-trifluoromethylphenol, m-methoxyphenol, p-chlorophenol, 2-bromo-4-methylphenol, 4-phenylphenol, 8-quinolinol, and estradiol.

5. The preparation method according to claim 1, characterized in that, The thiophenolic compounds are selected from any one of p-methylthiophenol, p-ethylthiophenol, p-isopropylthiophenol, 2,6-dimethylthiophenol, p-methoxythiophenol, p-fluorothiophenol, p-chlorothiophenol, p-bromothiophenol, 3,5-di(trifluoromethyl)thiophenol, 2-naphthiophenol, and 2-methylfuranthiophenol.

6. The preparation method according to claim 1, characterized in that, The copper catalyst is selected from any one of cesium carbonate, potassium tert-butoxide, sodium carbonate, triethylamine, pyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

7. The preparation method according to claim 1, characterized in that, The organic solvents mentioned in S1 and S2 are selected from any one of acetonitrile, 1,2-dichloroethane, tetrahydrofuran, N,N-dimethylformamide, and dichloromethane.

8. The preparation method according to claim 1, characterized in that, After the S2 reaction is completed, the process also includes a purification step for (Z)-1-aryl thioether-2-phenol ether-4-aryl-trisubstituted-1-butene-3-yne compounds.

9. The preparation method according to claim 8, characterized in that, The purification process specifically involves extracting, drying, vacuum distilling, and column chromatography to purify the reaction system after the S2 reaction.

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