A method for synthesizing 3-trifluoromethylsulfanyl-1h-inden-1-one compounds

Abstract

The application discloses a synthesis method of 3-trifluoromethylthio-1H-inden-1-ketone compounds and belongs to the field of organic chemistry. According to the method, 2-alkynyl aryl formaldehyde compounds and trifluoromethylthio silver are used as raw materials, and under the action of an oxidant and a catalyst, the synthesis of 3-trifluoromethylthio-1H-inden-1-ketone compounds can be rapidly realized. The method has wide substrate applicability, simple and easily-obtained raw materials and low economic cost. In addition, the method can realize the synthesis of target products, does not need catalyst catalysis and can obtain the target products in a good yield only by reacting for 4-6 hours. The target compounds have wide application in the fields of medicines, pesticides and functional materials.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 3-trifluoromethylthio-1H-inden-1-one compounds, belonging to the field of organic chemistry. Background Technology

[0002] The trifluoromethyl thio group (-SCF3) is an important fluorine-containing functional group with excellent lipophilicity, strong electron-withdrawing properties, and bioactivity, making it widely used in organic synthesis, medicinal chemistry, and materials science. The stability and relatively easy introduction of the trifluoromethyl thio group make it one of the most popular functional groups. Furthermore, indanone and its derivatives exhibit broad-spectrum bioactivity in anti-inflammatory, insecticidal, bactericidal, and antitumor activities. Combining the advantages of both groups in these areas, introducing a trifluoromethyl thio group into the indanone skeleton would undoubtedly endow the compound with some novel and unique properties. However, no methods have been reported for introducing a trifluoromethyl thio group onto the 3-carbon atom of indanone, mainly due to the lack of suitable chemical reaction methods and a sufficiently broad range of 1H-indan-1-one substrates for the synthesis of such compounds.

[0003] Therefore, developing a simple and mild direct trifluoromethylthiolation method to rapidly construct 3-trifluoromethylthio-1H-inden-1-one compounds is of great importance and practical value. Summary of the Invention

[0004] This invention develops a novel method for synthesizing 3-trifluoromethylthio-1H-inden-1-one compounds. By reacting 2-alkynylaryl formaldehydes with AgSCF3, an oxidant, and a catalyst, trifluoromethylthioindenone compounds are obtained through addition cyclization, thus conveniently achieving the synthesis of 1-trifluoromethylthioindenone derivatives.

[0005] The first objective of this invention is to provide a method for synthesizing 3-trifluoromethylthio-1H-indene-1-one compounds, comprising the following steps: in an organic solvent, a 2-alkynylaryl formaldehyde compound of formula (1), silver trifluoromethylthio (AgSCF3), and an oxidant undergo a cyclization reaction to synthesize 3-trifluoromethylthio-1H-indene-1-one compounds of formula (2);

[0006] Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen (F, Cl, Br), cyano, nitro, C1-C8 alkoxy, acyl, amide, ester, and heterocyclic; R 2 It is selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl, amide, ester and heterocyclic groups.

[0007] In one embodiment of the present invention, the aryl group includes substituted or unsubstituted benzene rings, naphthalene rings, and heteroaryl rings; the substitution can be one to three substitutions; the substituted group is selected from halogens, C1-C8 alkyl groups, C1-C8 alkoxy groups, ester groups, cyano groups, nitro groups, and heterocycles.

[0008] In one embodiment of the present invention, the acyl group is -COR. a R a It is H or C1-8 alkyl.

[0009] In one embodiment of the present invention, the amide group is -NHCOR. b R b It is H or C1-8 alkyl.

[0010] In one embodiment of the present invention, the ester group is -COOR. c R c It is a C1-8 alkyl group.

[0011] In one embodiment of the present invention, the heterocycle is a three- to six-membered ring containing 1 to 3 heteroatoms. The heteroatoms include N, O, and S.

[0012] In one embodiment of the present invention, the organic solvent includes any one or more of dimethyl sulfoxide (DMSO), dichloromethane (DCM), tetrahydrofuran (THF), and 1,2-dichloroethane (DCE). DMSO is preferred.

[0013] In one embodiment of the present invention, the oxidant is any one or more of potassium persulfate, sodium persulfate, ammonium persulfate, and oxygen. Sodium persulfate is preferred.

[0014] Optionally, a catalyst may be added to the cyclization reaction.

[0015] In one embodiment of the present invention, the catalyst is any one or more of cuprous iodide, potassium iodide, and elemental iodine. Cuprous iodide is preferred.

[0016] In one embodiment of the invention, the reaction temperature is 60°C-140°C, preferably 95-105°C.

[0017] In one embodiment of the present invention, the reaction time is 4-6 hours. Specifically, 4 hours is an option.

[0018] In one embodiment of the present invention, the molar ratio of the 2-alkynylaryl formaldehyde compound, silver trifluoromethyl sulfide, catalyst, and oxidant is 1:(1.5-2.5):(0-3.0):(2.0-4.0). Preferably, it is 1:2:1:3.

[0019] In one embodiment of the present invention, the reaction concentration of the 2-alkynylarylformaldehyde compound is 0.05-5 mmol / mL, more preferably 0.05-2 mmol / mL. Specifically, 0.1 mmol / mL is preferred.

[0020] In one embodiment of the invention, the trifluoromethyl thiolation / cyclization reaction is carried out under an inert atmosphere, such as at least one of nitrogen or argon. Nitrogen is preferred.

[0021] The second objective of this invention is to provide a novel, green, and economical synthesis method, comprising the following steps: Using 2-alkynylaryl formaldehyde compounds, silver trifluoromethyl sulfide, catalyst, and oxidant as raw materials, the crude product of 3-trifluoromethyl sulfide-1H-indene-1-one compounds was obtained by stirring and reacting at 95-105 °C for a period of time. Then, pure 3-trifluoromethyl sulfide-1H-indene-1-one compounds were obtained by filtration, washing, vacuum distillation, and column chromatography.

[0022] In one embodiment of the present invention, the separation and purification method employs rapid column chromatography to obtain the final product 3-trifluoromethylthio-1H-inden-1-one compounds.

[0023] In one embodiment of the present invention, the method is preferably carried out as follows: 2-alkynylaryl formaldehyde compound, silver trifluoromethyl sulfide, catalyst and oxidant are added to a reaction vessel containing acetonitrile solvent in a molar ratio of 1:2:1:3, stirred at 100°C for 2-6 hours, separated and purified to obtain the target product.

[0024] In one embodiment of the present invention, the reaction mechanism of the method is as follows: First, AgSCF3 reacts with CuI to generate CuSCF3, which has higher reactivity. Subsequently, under the oxidation of Na2S2O8, trifluoromethylthio radicals and sulfate radical anions are generated. The trifluoromethylthio radical attacks the alkynyl group in 2-alkynylarylformaldehyde to generate the corresponding alkenyl radical intermediate. The alkenyl radical adds to the carbonyl group of the aldehyde, undergoing intramolecular cyclization to form an alkoxy radical intermediate. This intermediate is oxidized and hydrogen-extracted by the sulfate radical anion, ultimately generating 3-trifluoromethylthio-1H-inden-1-one compounds.

[0025] A third objective of this invention is to provide the application of the synthesis method in the fields of pharmaceuticals, pesticides, and the preparation of functional materials.

[0026] Beneficial effects: (1) The method employed in this invention, under a nitrogen atmosphere, uses 2-alkynylarylcarboxaldehyde compounds, silver trifluoromethyl sulfide, and sodium persulfate as reactants, and cuprous iodide as a catalyst, to successfully construct the 3-trifluoromethyl sulfide-1H-inden-1-one compound skeleton through a one-pot reaction, thereby obtaining the target product. With cuprous iodide as the key catalyst, the main byproducts generated after the reaction are inorganic salts such as sodium iodide. These byproducts are insoluble in organic solvents and can be directly separated from the reaction system through simple filtration, significantly reducing the time and cost required for post-processing.

[0027] (2) The method of this invention has broad substrate applicability, uses simple and readily available raw materials, and has relatively low economic cost. Furthermore, the catalytic system exhibits good tolerance to various functional groups in the substrate (such as ester groups, amide groups, halogens, etc.), eliminating the need for additional protection / deprotection operations on the substrate, thus simplifying the synthetic route and improving the practicality of the reaction. In addition, this method requires only 4 hours of reaction time to synthesize the target product, achieving a high yield and demonstrating rapid and efficient characteristics.

[0028] (3) The synthesis method of the present invention enables the one-step synthesis of 3-trifluoromethylthio-1H-inden-1-one compounds from readily available o-alkynylbenzaldehyde compounds under relatively simple conditions. The target compounds have wide application value in the fields of medicine, pesticides, and functional materials.

[0029] (4) The reaction of the present invention can be carried out under mild conditions, which effectively avoids equipment damage and safety risks caused by high temperature and high pressure, while reducing the decomposition of reactants and the occurrence of side reactions. Attached Figure Description

[0030] Figure 1 This is a synthetic route diagram of the present invention. Detailed Implementation

[0031] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0032] The following are specific embodiments of the present invention.

[0033] 1. The following examples involve 2-phenylethynylbenzaldehyde (CAS: 59046-72-9); 2-(4-methoxyphenylethynyl)benzaldehyde (CAS: 176910-67-1); 2-(4-phenylphenylethynyl)benzaldehyde (CAS: 1017235-21-0); 2-(4-tert-butylphenylethynyl)benzaldehyde (CAS: 221458-82-8); 2-(4-ethylphenylethynyl)benzaldehyde (CAS: 1383274-53-0); 2-(3-methylphenylethynyl)benzaldehyde (CAS: 1283638-37-8); and silver trifluoromethyl sulfide (CAS: 1647073-46-8), which were synthesized by methods reported in existing literature.

[0034] Cuprous iodide, dimethyl sulfoxide, ethyl acetate, sodium persulfate (Na2S2O4), and anhydrous MgSO4 were all purchased from Adamas.

[0035] 2. The chromatographic separation and purification method involved in the following examples: Column type: G3, stationary phase: silica gel (particle size 200-300 mesh), mobile phase: V 石油醚 :V 乙酸乙酯 =100:1.

[0036] 3. The synthesis route diagram of the embodiments of the present invention, as follows: Figure 1 As shown, specifically: Using 2-alkynylaryl carboxaldehyde compounds and silver trifluoromethyl sulfide as raw materials, cuprous iodide and sodium persulfate are added, and dimethyl sulfoxide is used as the reaction solvent. The reaction is carried out at 100°C for 2-6 hours to obtain the target compound. The reaction formula is as follows: Figure 1 .

[0037] Example 1: Synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0038] Under nitrogen protection, p-2-(4-methoxyphenylethynyl)benzaldehyde (118.1 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 117.7 mg of the target compound, with a yield of 70%.

[0039] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 3.86 (s, 3H), 7.00 (d,J = 9.2 Hz, 2H), 7.30(t,J = 7.4 Hz, 1H), 7.42 (d, J = 7.3 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.55(d, J = 7.1 Hz, 1H), 7.60 (d, J = 7.4 Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ -37.61 (s, 3F). 13 C NMR (101 MHz, CDCl3) δ 55.54 (s), 114.11 (s), 121.61 (s), 121.70 (s), 123.46 (s), 127.40 (q), 129.36 (s), 132.00 (s), 135.08 (s),137.17 (s), 144.77 (s), 144.99 (s), 161.01 (s), 194.32 (s). Example 2: Synthesis of 2-phenyl-3-trifluoromethylthio-1H-inden-1-one

[0040] Under nitrogen protection, 2-phenylethynylbenzaldehyde (103.1 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 70 mg of the target compound, with a yield of 46%.

[0041] The obtained product was analyzed and characterized, and the specific data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.33 (t, J = 7.4 Hz, 1H), 7.46 (d, J = 6.1Hz, 4H), 7.51 (d, J = 7.4 Hz, 1H), 7.56 (t, J = 7.4 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -37.38 (s, 3F). 13 C NMR (101 MHz, CDCl3) δ 121.92 (d, J = 1.9 Hz), 123.56 (s), 128.48 (s), 128.85 (q, J = 312.1 Hz), 129.23 (s), 129.38 (s), 129.75 (s), 129.78 (s), 130.34 (s), 135.06 (s), 139.68 (s), 144.51 (s), 145.39 (s), 193.75 (s). Example 3: Synthesis of 2-(4-phenylphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0042] Under nitrogen protection, 2-(4-phenylphenylethynyl)benzaldehyde (141.2 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 105 mg of the target compound, with a yield of 55%.

[0043] The obtained product was analyzed and characterized, and the specific data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.35 (dt, J = 14.4, 7.3 Hz, 2H), 7.46 (t, J= 6.9 Hz, 3H), 7.52 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.1 Hz, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.69 (q, J = 6.3 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -37.31 (s,3F). 13 C NMR (101 MHz, CDCl3) δ 121.93 (s), 123.60 (s), 127.19 (s), 127.38 (s), 128.00 (s), 128.15 (s), 128.65 (q), 129.09 (s), 129.42 (s), for C 22 H 13 F3OSH (M+H) + :383.0717; found: 383.0696. Example 4: Synthesis of 2-(4-tert-butylphenyl)-5-methyl-3-trifluoromethylthio-1H-inden-1-one

[0044] Under nitrogen protection, 2-(4-tert-butylphenylethynyl)benzaldehyde (131.2 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 54 mg of the target compound, with a yield of 31%.

[0045] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 3.85 (s, 3H), 6.99 (d, J = 8.6Hz, 1H), 7.08 (d, J = 7.4 Hz, 1H), 7.22 (s, 1H), 7.43 (d, J = 7.3 Hz, 1H),7.60 (d, J = 8.8 Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ -37.75 (s, 3F). 13 C NMR (101MHz, CDCl3) δ 22.44 (s), 55.51 (s), 114.06 (s), 121.87 (s), 122.75 (s), 123.57 (s), 127.07 (s), 128.99 (q), 129.42 (s), 131.98 (s), 136.49 (s),145.30 (s), 145.42 (s), 146.39 (s), 160.95 (s), 193.90 (s). HRMS (APGC) m / zcalcd. for C 18 H 13 F3OSH (M+H) + : 351.0667; found: 351.0667. Example 5: Synthesis of 2-(4-ethylphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0046] Under nitrogen protection, 2-(4-ethylphenylethynyl)benzaldehyde (117.1 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 146 mg of the target compound, with a yield of 79%.

[0047] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 3.87 (s, 3H), 7.00 (d, J = 8.9 Hz, 2H), 7.28 (d, J = 8.1 Hz, 1H), 7.40 (s, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 8.9Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ -37.65 (s, 3F). 13 C NMR (101 MHz, CDCl3) δ55.57 (s), 114.20 (s), 121.36 (s), 122.31 (s), 124.43 (s), 127.49 (s), 128.85(q, J = 312.5 Hz), 129.03 (s), 132.11 (s), 135.38 (s), 141.60 (s), 145.99(s), 147.01 (s), 161.33 (s), 192.89 (s). HRMS (APGC) m / z calcd. for C 17 H 10 F3OSH(M+H) + : 371.0120; found: 371.0103. Example 6: Synthesis of 2-(3-methylphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0048] Under nitrogen protection, 2-(3-methylphenylethynyl)benzaldehyde (110.1 mg, 0.5 mmol), silver trifluoromethyl sulfide (208.9 mg, 1.0 mmol), cuprous iodide (95.23 mg, 0.5 mmol), sodium persulfate (357.15 mg, 1.5 mmol), and dimethyl sulfoxide (5 mL) were added to a 25 mL reaction tube equipped with a stir bar and reacted at 100 °C and 800 rpm for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with diatomaceous earth, and the filter residue was washed with 30 mL of ethyl acetate. The organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 64 mg of the target compound, with a yield of 36%.

[0049] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 3.87 (s, 3H), 6.95 (t, J = 9.8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.2 Hz, 1H), 7.51-7.59 (m, 1H), 7.62 (d, J= 8.3 Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ -101.44 (s, 1F), -37.71 (s, 3F). 13 CNMR (101 MHz, CDCl3) δ 55.57 (s), 110.47 (d, J = 26.4 Hz), 114.20 (s), 115.01(s), 115.25 (s), 121.41 (s), 125.55 (d, J = 10.1 Hz), 128.88 (q, J = 312.4Hz), 132.12 (s), 146.29 (s), 148.51 (d, J = 9.8 Hz), 161.32 (s), 166.36 (s), 168.91 (s), 192.51 (s). In this invention, we also replaced 2-(4-methoxyphenylethynyl)benzaldehyde with other substitutions to obtain more corresponding target compounds. Through the synthesis of dozens of extended compounds, we found that the method of this invention is universal and can effectively prepare the target compounds.

[0050] Example 7: Effect of different catalysts on the synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one Referring to Example 1, the catalyst was replaced by potassium iodide (285.7 mg, 1.72 mmol), elemental iodine (285.7 mg, 1.13 mmol), NBS (285.7 mg, 1.61 mmol), and silver hexafluoroantimonate (285.7 mg, 0.83 mmol), respectively, with other conditions remaining unchanged, to synthesize 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one. Specific yield results are shown in Table 1.

[0051] Table 1. Effect of different catalysts on the synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0052] The results showed that using potassium iodide, elemental iodine, NBS, and silver hexafluoroantimonate instead of cuprous iodide in Example 1 as catalysts failed to yield the target product, and the yields were all worse than those in Example 1.

[0053] Example 8: Effect of different solvents on the synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one Referring to Example 1, the solvents were replaced with N,N-dimethylformamide (DMF), acetonitrile (MeCN), acetonitrile:water = 1:1, and dichloromethane (DCM) respectively, while keeping other conditions unchanged, to synthesize 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one. Specific yield results are shown in Table 2.

[0054] Table 2. Effects of different solvents on the synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one

[0055] The results showed that replacing dimethyl sulfoxide in Example 1 with N,N-dimethylformamide, acetonitrile, or acetonitrile:water = 1:1 as the solvent could yield the target product, but the product yield was worse than that in Example 1.

[0056] Example 9: Synthesis of 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one at different reaction temperatures Referring to Example 1, the reaction temperature was replaced by 25 °C, 80 °C, and 120 °C respectively, while other conditions remained unchanged, to synthesize 2-(4-methoxyphenyl)-3-trifluoromethylthio-1H-inden-1-one.

[0057] The specific yield results are shown in Table 3.

[0058] Table 3. Effect of different reaction temperatures on the synthesis of 2-(4-methoxybenzene)-3-trifluoromethylthio-1H-inden-1-one

[0059] The results showed that replacing 100℃ in Example 2 with 80℃ or 120℃ both yielded the target product, but the product yield was not significantly different from that in Example 1. The yield decreased more significantly when the temperature reached 25℃.

[0060] Example 10: Molar ratio of different 2-alkynylaryl formaldehyde compounds, silver trifluoromethyl sulfide, oxidant, and catalyst Referring to Example 1, the molar ratios of 2-alkynylaryl formaldehyde compounds, silver trifluoromethyl sulfide, oxidant, and catalyst were adjusted to 1:2:1.5:3, 1:2:2:3, 1:2.5:1:3, 1:1.5:1:3, 1:2:1:2.5, and 1:2:1:3.5, while keeping other conditions unchanged, to synthesize 2-(4-methoxyphenyl)-3-trifluoromethyl sulfide-1H-inden-1-one. Specific yield results are shown in Table 4.

[0061] Table 4. Effect of different molar ratios of 2-alkynylaryl formaldehydes, silver trifluoromethyl thioide, cuprous iodide, and oxidant on the synthesis of 2-(4-methoxyphenyl)-3-trifluoromethyl thio-1H-inden-1-one.

[0062]

[0063] The results showed that replacing the 1:2:1:3 ratio in Example 1 with the molar ratios of 2-alkynylaryl formaldehyde, silver trifluoromethyl sulfide, cuprous iodide, and oxidant of 1:2:1.5:3, 1:2:2:3, 1:2.5:1:3, 1:1.5:1:3, 1:2:1:2.5, and 1:2:1:3.5 could yield the target product, but the yield of the product was worse than that of Example 1.

[0064] Comparative Example 1: Referring to Example 1, sodium persulfate was not added, and everything else remained the same.

[0065] The results showed that without the addition of sodium persulfate, the yield of the product was 0%.

[0066] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for synthesizing 3-trifluoromethylthio-1H-inden-1-one compounds, characterized in that, The method involves using 2-alkynylaryl formaldehyde compounds of formula (1) and silver trifluoromethyl sulfide as reactants in an organic solvent to carry out a trifluoromethyl sulfidation / cyclization reaction, thereby synthesizing 3-trifluoromethyl sulfide-1H-inden-1-one compounds of formula (2). Among them, R 1 Selected from H, C1-C8 alkyl, C1-C8 haloalkyl, aryl, halogen, cyano, nitro, C1-C8 alkoxy, acyl and amide groups, and heterocycles; R 2 It is selected from C1-C8 alkyl, C1-C8 haloalkyl, aryl, C1-C8 alkoxy, acyl and amide groups and heterocycles.

2. The method according to claim 1, characterized in that, The organic solvent includes any one or more of acetonitrile, dichloromethane, tetrahydrofuran, and dimethyl sulfoxide.

3. The method according to claim 1, characterized in that, The oxidant is any one or more of potassium persulfate, sodium persulfate, ammonium persulfate, and oxygen.

4. The method according to any one of claims 1 to 3, characterized in that, Trifluoromethyl sulfide / cyclization reaction is carried out in the presence of a catalyst.

5. The method according to claim 4, characterized in that, The catalyst is any one or more of cuprous iodide, potassium iodide, elemental iodine, and N-bromosuccinimide.

6. The method according to claim 1, characterized in that, The reaction temperature is 60℃-140℃.

7. The method according to claim 4, characterized in that, The molar ratio of the 2-alkynylaryl formaldehyde compound, silver trifluoromethyl sulfide, catalyst, and oxidant is 1:(1.5-2.5):(0-3.0):(2.0-4.0).

8. The method according to claim 1, characterized in that, The reaction concentration of the 2-alkynylaryl formaldehyde compound is 0.05-5 mmol / mL.

9. The method according to claim 1, characterized in that, The trifluoromethyl sulfide / cyclization reaction is carried out in an inert gas atmosphere; preferably, the inert atmosphere is selected from at least one of nitrogen or argon.

10. The application of the method according to any one of claims 1-9 in the fields of pharmaceuticals, pesticides and functional materials preparation.

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