A method for synthesizing organic thioether compounds

Abstract

The invention discloses a method for synthesizing an organic sulfide compound, and belongs to the field of organic synthesis. The invention uses an alkenyl sulfide salt shown in formula I as a raw material, and reacts to obtain an organic sulfide compound shown in formula II without metal catalysis. The raw materials of the method of the invention are cheap and easy to obtain, and no metal catalyst is required. The method is green, environmentally friendly and pollution-free, and has the advantages of a wide range of substrates, high yield, simple operation, and easy separation and purification of products. #imgabs0#

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing an organic thioether compound. Background Art

[0002] Organic sulfide compounds are widely present in food, medicine, pesticides, natural products and functional materials, and are closely related to our lives and production, especially in the research and development of various new drugs. It is reported that various organic sulfide compounds have a wide spectrum of biological activities, such as antibacterial, insecticidal (compound A), herbicidal, antiviral, antidepressant (compound B), antitumor, etc. In addition, tetrahydrothiophene, as a special sulfur-containing five-membered heterocyclic compound, its derivatives also have a variety of biological and pharmacological activities, and are widely present in alkaloids or drugs, such as certain antagonists (compound C), oxidative enzyme inhibitors, antioxidant active substances and plant growth regulators. All of the above belong to the application scope of organic sulfide compounds. Although these compounds are very important, the preparation of these high-value compounds is still very challenging, so the development of mild and effective synthesis methods still receives widespread attention.

[0003]

[0004] Existing methods for synthesizing organic sulfide compounds have the following main disadvantages: most of them require transition metal catalysis or use toxic sulfur reagents, which are costly and cause serious environmental pollution. Summary of the invention

[0005] In view of the fact that the existing synthesis pathways require the participation of transition metals and are costly, the purpose of the present invention is to provide a cheap and environmentally friendly method for synthesizing organic sulfide compounds. The method has the advantages of simple operation, no catalyst, a wide range of applicable substrates, high yield, and easy product separation.

[0006] To achieve the above object, the present invention adopts the following technical solution:

[0007] A method for synthesizing an organic sulfide compound without metal catalysis, using an alkenyl sulfonium salt of formula I as a raw material, reacting in the presence of a base to obtain an organic sulfide compound of formula II;

[0008]

[0009] Wherein, R1 is selected from substituted or unsubstituted aryl, the substitution is mono- to tri-substituted, and the substituents are: halogen (F, Cl, Br, I), C1-C4 alkyl, C1-C4 alkoxy, aryl; R2 and R3 are selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, or for

[0010] “---” means there is a covalent bond or no covalent bond; Selected from or Z1 is CHR4, Z2 is C1-C4 alkyl or phenyl; R4 is H or C1-C4 alkyl.

[0011] In one embodiment of the present invention, the aryl group is a benzene ring or a naphthalene ring.

[0012] In one embodiment of the present invention, R1 is specifically selected from:

[0013] In one embodiment of the present invention, R2 and R3 are independently selected from hydrogen, methyl, phenyl, isopropyl, or for

[0014] In one embodiment of the present invention, Specific selection:

[0015] In one embodiment of the present invention, Specific selection:

[0016] In one embodiment of the present invention, the reaction is carried out in an organic solvent, specifically any one or more of dichloromethane, 1,4-dioxane, tetrahydrofuran, and toluene.

[0017] In one embodiment of the present invention, the base comprises sodium hydride, sodium tert-butoxide, sodium hydroxide or potassium tert-butoxide.

[0018] In one embodiment of the present invention, the reaction temperature is 0°C to 60°C, and the reaction time is 3 to 12 hours.

[0019] In one embodiment of the present invention, the reaction temperature is further preferably 0-30°C.

[0020] In one embodiment of the present invention, the reaction time can be specifically selected to be 4 hours.

[0021] In one embodiment of the present invention, the molar ratio of the alkenyl sulfonium salt represented by Formula I to the base is 1.0:1.0-2.0, and can be specifically 1.0:1.5.

[0022] In one embodiment of the present invention, the amount of the organic solvent added is 2-10 mL / mmol based on the amount of the alkenyl sulfonium salt represented by Formula I. Specifically, it can be 2-5 mL / mmol.

[0023] In one embodiment of the present invention, the reaction atmosphere is air, oxygen or nitrogen.

[0024] In one embodiment of the present invention, after the reaction, the product is purified by silica gel column chromatography.

[0025] The purification method comprises: after the reaction is completed, adding column chromatography silica gel, distilling under reduced pressure to remove the solvent, spinning to dry until the silica gel adsorbs the product in powder form, then loading the product onto a column, eluting with petroleum ether, collecting the product, and evaporating and concentrating the product to obtain an organic sulfide compound.

[0026] Beneficial effects:

[0027] Compared with the prior art, the present invention has the following advantages over the prior art in synthesizing such organic sulfide compounds: first, no catalyst is required, the raw materials are easily available, the catalytic efficiency is high, and the product is easy to separate and purify. Therefore, it is of great significance to develop a method for synthesizing organic sulfide compounds. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments.

[0029] The vinyl sulfonium salts of the present invention can be prepared according to existing literature, such as F. Berger, EMAlvarez, T. Ritter, et al. Cine-Substitutions at Five-Membered Hetarenes Enabled by Sulfonium Salts. Org. Lett. 2020, 22, 5671-5674. The present invention provides the following synthesis method:

[0030] Under argon or nitrogen conditions, tetramethylene sulfoxide (5.5mmol, 572mg) was dissolved in 25mL of dichloromethane, the mixture was stirred at -40℃, and then α-substituted aryl olefin (5.0mmol) and trifluoromethanesulfonic anhydride (5.5mmol, 1.55g) were added dropwise to the reaction, and the reaction was carried out at -40℃ for 30 minutes, and then the reaction was continued at 0℃ for 3h, and the reaction was tracked by TLC spot plate detection. After the reaction was completed, the solvent was removed under vacuum. Recrystallization was carried out with dichloromethane and ether to obtain a white solid, which was the corresponding sulfonium salt.

[0031] The synthetic route of sulfonium salt is:

[0032] Where R1 is:

[0033] in, for:

[0034] The synthetic route of the target product is:

[0035] Example 1

[0036] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0037]

[0038] The preparation method is as follows: under air conditions, α-methylphenyltetrahydrothiothionium salt (1.0 mmol, 354.1 mg) is added. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 93% (189.8mg). The substance is a colorless oily liquid.

[0039] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.40–7.37(m,2H),7.34–7.28(m,2H),7.28–7.25(m,1H),5.30(d,J=1.5Hz,1H),5.12(d,J=1.3Hz, 1H),3.48–3.39(m,1H),2.93–2.87(m,1H),2.85–2.76(m,3H),2.11–1.96(m,2H),1.89–1.80(m,1H),1.65–1.57(m,1H). 13 C NMR (101MHz, CDCl3) δ147.0,140.7,128.3,127.5,126.2,113.9,47.0,43.5,36.8,32.3,30.1.

[0040] Example 2

[0041] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0042]

[0043] The preparation method is as follows: α-methyl p-phenylstyrene sulfonium salt (1.0 mmol, 430.1 mg) is added under air. tBuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 85% (238.1mg). The substance was a white solid.

[0044] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.63–7.56(m,4H),7.50–7.43(m,4H),7.37–7.33(m,1H),5.39(s,1H),5.17(s,1H),3.52 –3.48(m,1H),2.95–2.92(m,1H),2.86–2.82(m,3H),2.13–2.02(m,2H),1.91–1.84(m,1H),1.68–1.61(m,1H). 13 C NMR (101MHz, CDCl3) δ146.5,140.7,140.3,139.6,128.7,127.3,127.0,126.9,126.6,113.9,47.0,43.4,36.8,32.4,30.2.HRMS m / z(ESI)calcd for C 19 H 21 S(M+H) + 281.1358, found 281.1357.

[0045] Example 3

[0046] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0047]

[0048] The preparation method is as follows: α-methyl p-bromostyrylsulfonium salt (1.0 mmol, 431.9 mg) is added under air. tBuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 80% (224.0mg). The substance is a colorless oily liquid.

[0049] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.47–7.43(m,2H),7.27–7.24(m,2H),5.29(s,1H),5.15(s,1H),3.43–3.37(m, 1H),2.93–2.88(m,1H),2.84–2.70(m,3H),2.11–1.97(m,2H),1.88–1.81(m,1H),1.64–1.56(m,1H). 13 C NMR(126MHz, CDCl3)δ146.0,139.7,131.4,127.9,121.4,114.5,46.9,43.3,36.8,32.3,30.1.HRMS m / z(ESI)calcd for C 13 H 14 BrSNa(M+Na) + 304.9970, found 304.9968.

[0050] Example 4

[0051] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0052]

[0053] The preparation method is as follows: under air conditions, α-methyl m-chlorostyrene sulfonium salt (1.0 mmol, 239.1 mg) is added. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 54% (128.6mg). The substance is a colorless oily liquid.

[0054] Characterization data: 1 H NMR(400MHz, CDCl3)δ7.34(s,1H),7.23(s,3H),5.29(s,1H),5.14(s,1H),3.42–3.35 (m,1H),2.91–2.68(m,4H),2.07–1.98(m,2H),1.87–1.79(m,1H),1.62–1.52(m,1H). 13 C NMR (101MHz, CDCl3) δ145.9,142.7,134.2,129.6,127.5,126.4,124.4,115.1,46.8,43.3,36.8,32.4,30.2.HRMS m / z(ESI)calcd for C 13 H 16 ClS(M+H) + 239.0656, found 238.0655.

[0055] Example 5

[0056] The structural formula of the tetrahydrothiophene derivatives prepared in this example is as follows:

[0057]

[0058] The preparation method is as follows: α-methyl 2,4-dichlorostyrene sulfonium salt (1.0 mmol, 422.0 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 78% (212.2mg). The substance is a colorless oily liquid.

[0059] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.37 (d, J = 2.1Hz, 1H), 7.22–7.19 (m, 1H), 7.15–7.13 (m, 1H), 5.32 (s, 1H), 5.03 (s, 1H), 3. 28–3.24(m,1H),2.90–2.81(m,3H),2.64–2.58(m,1H),2.08–2.02(m,2H),1.87–1.83(m,1H),1.62–1.56(m,1H). 13C NMR(101MHz, CDCl3)δ145.9,139.5,133.5,132.8,131.4,129.3,126.9,117.8,46.9,44.5,37.0,32.4,30.2.HRMS m / z(ESI)calcd for C 13 H 14 Cl2NaS(M+Na) + 295.0085, found 295.0087.

[0060] Example 6

[0061] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0062]

[0063] The preparation method is as follows: 1-isopropenylnaphthylsulfonium salt (1.0 mmol, 404.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 87% (221.1mg). The substance is a colorless oily liquid.

[0064] Characterization data: 1 H NMR (500MHz, CDCl3) δ8.11–8.07(m,1H),7.88–7.85(m,1H),7.79(d,J=8.3Hz,1H),7.52–7.32(m,3H),7.33(dd,J=7.0,1.3Hz,1H),5.50(d,J=1.6 Hz,1H),5.17(d,J=1.9Hz,1H),3.39–7.34(m,1H),2.95–2.88(m,2H),2.8 5–2.75(m,2H),2.11–2.01(m,2H),1.89–1.80(m,1H),1.66–1.59(m,1H). 13C NMR (126MHz, CDCl3) δ147.1,140.4,133.7,131.2,128.3,127.4,125.8,125.7,125.7,125.3,125.2,117.0,47.0,46.7,37.0,32.3,30.3.HRMS m / z(ESI)calcd for C 17 H 19 S(M+H) + 255.1202, found 255.1203.

[0065] Example 7

[0066] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0067]

[0068] The preparation method is as follows: α-methyl 1,2-methylenedioxyphenylenesulfonium salt (1.0 mmol, 398.0 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 89% (220.7mg). The substance is a colorless oily liquid.

[0069] Characterization data: 1 H NMR (500MHz, CDCl3) δ6.90–6.85(m,2H),6.76(d,J=8.0Hz,1H),5.95(s,2H),5.20(d,J=1.4Hz,1H),5.04(d,J=1.4Hz,1H),3.46– 3.40(m,1H),2.92–2.87(m,1H),2.84–2.80(m,1H),2.79–2.70(m,2H),2.10–1.98(m,2H),1.89–1.80(m,1H),1.63–1.57(m,1H). 13 C NMR (126MHz, CDCl3) δ147.7,147.0,146.5,135.0,119.7,113.0,108.0,106.8,101.0,47.0,43.7,36.7,32.3,30.1.HRMS m / z(ESI)calcd for C14 H 17 O2S(M+H) + 249.0944, found 249.0944.

[0070] Example 8

[0071] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0072]

[0073] The preparation method is as follows: under air conditions, α-ethylstyrene sulfonium salt (1.0 mmol, 368.1 mg) is added. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 83% (180.9mg). The substance is a colorless oily liquid.

[0074] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.39–7.35(m,2H),7.34–7.24(m,3H),5.21(s,1H),5.13(s,1H),3.54–3.48(m,1H),2.88– 2.80(m,2H),2.80–2.72(m,1H),2.21–2.13(m,2H),1.91–1.80(m,1H),1.53–1.49(m,1H),1.18(d,J=6.9Hz,3H). 13 C NMR (101MHz, CDCl3) δ154.3,142.6,128.1,127.2,127.0,112.6,53.7,45.9,34.8,32.3,31.3,19.2.HRMS m / z(ESI)calcd for C 14 H 19 S(M+H) + 219.1202, found 219.1201.

[0075] Example 9

[0076] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0077]

[0078] The preparation method is as follows: α-cyclopentylstyrene sulfonium salt (1.0 mmol, 408.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (2mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 72% (185.8mg). The substance is a colorless oily liquid.

[0079] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.31–7.27(m,3H),7.25–7.22(m,2H),5.31(d,J=1.4Hz,1H),5.03(d,J=1.4Hz,1H),3.89(dd,J=9.4,6.4Hz,1H), 2.83–2.79(m,2H),2.16–2.11(m,1H),2.05–1.95(m,2H),1.94–1.85(m,2H),1.83–1.78(m,1H),1.74–1.65(m,4H),1.63–1.55(m,2H). 13 C NMR (126MHz, CDCl3) δ154.9,143.1,128.7,127.6,126.6,115.6,56.1,55.5,35.9,33.2,32.4,31.5,31.4,24.1,24.0.HRMS m / z(ESI)calcd for C 17 H 23 S(M+H) + 259.1515, found 259.1516.

[0080] Example 10

[0081] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0082]

[0083] The preparation method is as follows: α-methyl p-chlorostyrene sulfonium salt (1.0 mmol, 424.0 mg) is added under air. tBuOK (1.5 equiv, 168.3 mg) was added to a 25 ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5 mL), and the reaction was stirred at room temperature for 4 h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 83% (227.4 mg). The substance is a colorless oily liquid.

[0084] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.39–7.35(m,2H),7.33–7.29(m,6H),7.24–7.21(m,H),5. 37(d,J=1.1Hz,1H),5.17(d,J=1.3Hz,1H),3.04–3.01(m,2H),2.85–2.82(m,2H). 13 C NMR(126MHz, CDCl3)δ145.3,138.6,136.1,133.3,129.4,128.8,128.5,127.3,126.0,114.2,35.0,32.3.HRMS m / z(ESI)calcd for C 16 H 16 ClS(M+H) + 275.0656, found 275.0655.

[0085] Embodiment 11

[0086] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0087]

[0088] The preparation method is as follows: under air conditions, α-methyl o-chlorostyrene sulfonium salt (1.0 mmol, 424.0 mg) is added. t BuOK (1.5 equiv, 168.3 mg) was added to a 25 ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5 mL), and the reaction was stirred at room temperature for 4 h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 83% (221.9 mg). The substance is a colorless oily liquid.

[0089] Characterization data: 1H NMR (500MHz, CDCl3) δ7.42–7.37(m,1H),7.33–7.27(m,4H),7.25–7.22(m,3H),7.21–7.17( m,1H),5.33(d,J=1.4Hz,1H),5.11(d,J=1.4Hz,1H),3.00–2.97(m,2H),2.85–2.82(m,2H). 13 C NMR (126MHz, CDCl3) δ146.4,140.7,136.3,132.1,130.6,129.5,129.1,128.8,128.5,126.6,125.8,116.9,36.1,31.8.HRMS m / z(ESI)calcd forC 16 H 16 ClS(M+H) + 275.0656, found 275.0656.

[0090] Example 12

[0091] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0092]

[0093] The preparation method is as follows: 2-isopropenylnaphthylsulfonium salt (1.0 mmol, 404.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 72% (208.9mg). The substance is a colorless oily liquid.

[0094] Characterization data: 1 H NMR(500MHz, CDCl3)δ7.87–7.81(m,4H),7.59(dd,J=8.5,1.9Hz,1H),7.54–7.48(m,2H),7.40–7.38(m,2H),7.34–7 .31(m,2H),7.25–7.22(m,1H),5.54(d,J=1.1Hz,1H),5.27(d,J=1.2Hz,1H),3.12–3.09(m,2H),3.01–2.98(m,2H). 13C NMR (126MHz, CDCl3) δ146.3,137.4,136.2,133.3,132.8,129.4,128.9,128. 1,128.0,127.5,126.2,126.0,125.9,124.7,124.5,114.3,35.3,32.6.HRMS m / z(ESI)calcd for C 20 H 19 S(M+H) + 291.1202, found 291.1202.

[0095] Embodiment 13

[0096] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0097]

[0098] The preparation method is as follows: α-ethyl p-chlorostyrenesulfonium salt (1.0 mmol, 438.0 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 84% (242.0mg). The substance is a colorless oily liquid.

[0099] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.26–7.20(m,6H),7.17–7.14(m,3H),5.22(s,1H),5.12(s,1H),3.09(d d,J=12.7,4.9Hz,1H),2.88–2.83(m,1H),2.74(dd,J=12.7,8.4Hz,1H),1.26(d,J=6.7Hz,3H). 13 C NMR (126MHz, CDCl3) δ151.6,140.3,136.6,133.2,129.5,128.8,128.4,128.0,126.0,112.9,40.1,37.7,19.0.HRMS m / z(ESI)calcd forC 17 H 18 ClS(M+H) +289.0812, found 289.0812.

[0100] Embodiment 14

[0101] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0102]

[0103] The preparation method is as follows: α-benzylstyrene sulfonium salt (1.0 mmol, 466.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 82% (259.1mg). The substance is a colorless oily liquid.

[0104] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.37–7.32(m,8H),7.31–7.24(m,6H),7.23–7.19(m,1H),5.54(s,1H), 5.29(s,1H),4.32–4.04(m,1H),3.55(dd,J=12.8,7.1Hz,1H),3.39(dd,J=12.8,8.0Hz,1H). 13 C NMR (126MHz, CDCl3) δ149.9,141.6,141.3,136.7,129.4,128.8,128.4,128.2,128.1,127.4,126.8,126.7,126.0,114.3,49.9,39.0.HRMS m / z(ESI)calcd for C 22 H 21 S(M+H) + 317.1358, found 317.1360.

[0105] Embodiment 15

[0106] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0107]

[0108] The preparation method is as follows: α-ethyl p-chlorostyrenesulfonium salt (1.0 mmol, 376.0 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and finally the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 89% (201.1mg). The substance is a colorless oily liquid.

[0109] Characterization data: 1 H NMR(500MHz, CDCl3)δ7.28–7.23(m,4H),5.20(s,1H),5.09(s,1H),2.87–2.81(m,1H),2.64 (dd,J=12.7,5.1Hz,1H),2.39(dd,J=12.7,8.3Hz,1H),2.04(s,3H),1.21(d,J=6.8Hz,3H). 13 C NMR(126MHz, CDCl3)δ152.0,140.6,133.2,128.4,128.0,112.6,40.9,38.0,19.2,16.3.HRMS m / z(ESI)calcd for C 12 H 16 S(M+H) + 227.0656, found 227.0657.

[0110] Example 16

[0111] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0112]

[0113] The preparation method is as follows: α-ethyl p-fluorostyrene sulfonium salt (1.0 mmol, 360.0 mg) is added under air. tBuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 90% (189.7mg). The substance is a colorless oily liquid.

[0114] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.33–7.29(m,2H),7.03–6.99(m,2H),5.20(s,1H),5.09(s,1H),2.90–2.85(m, 1H), 2.68 (dd, J=12.8, 5.2Hz, 1H), 2.42 (dd, J=12.8, 8.4Hz, 1H), 2.07 (s, 3H), 1.24 (d, J=6.8Hz, 3H). 13 C NMR (126MHz, CDCl3) δ162.2 (d, J = 246.2Hz), 152.1, 138.1 (d, J = 3.1Hz), 128.3 (d, J = 7.8Hz), 115.0 (d, J = 21.1Hz), 112.2, 40.9, 38.2, 19.2, 16.3. 19 F NMR(471MHz,CDCl3)δ-115.38.HRMS m / z(ESI)calcd forC 12 H 16 FS(M+H) + 211.0951, found 211.0950.

[0115] Embodiment 17

[0116] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0117]

[0118] The preparation method is as follows: α-benzylstyrene sulfonium salt (1.0 mmol, 404.1 mg) is added under air. tBuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 85% (216.0mg). The substance is a colorless oily liquid.

[0119] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.33–7.27(m,6H),7.25–7.21(m,4H),5.48(d,J=0.8Hz,1H),5.24(t,J=1.0Hz, 1H), 4.10 (t, J = 7.0Hz, 1H), 3.11 (dd, J = 12.8, 6.7Hz, 1H), 2.94 (dd, J = 12.8, 8.4Hz, 1H), 2.05 (s, 3H). 13 C NMR (126MHz, CDCl3) δ150.3,141.9,141.7,128.4,128.2,128.1,127.3,126.8,126.7,114.0,50.4,39.8,16.4.HRMS m / z(ESI)calcd for C 17 H 19 S(M+H) + 255.1202, found 255.1203.

[0120] Embodiment 18

[0121] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0122]

[0123] The preparation method is as follows: α-isopropylstyrene sulfonium salt (1.0 mmol, 356.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 88% (181.4mg). The substance is a colorless oily liquid.

[0124] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.31–7.25(m,3H),7.22–7.20(m,2H),5.23(d,J=1.5Hz,1H),4.92(d,J=1.5Hz,1H),2.58(s,2H),2.10(s,3H),1.22(s,6H). 13 C NMR(126MHz, CDCl3)δ156.4,142.6,128.9,127.4,126.5,114.1,47.1,40.7,27.2,17.6.HRMSm / z(ESI)calcd for C 13 H 19 S(M+H) + 207.1202, found 207.1204.

[0125] Embodiment 19

[0126] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0127]

[0128] The preparation method is as follows: α-cyclopentylstyrene sulfonium salt (1.0 mmol, 382.1 mg) is added under air. t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and finally the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 63% (146.2mg). The substance is a colorless oily liquid.

[0129] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.33–7.27(m,5H),5.26(d,J=1.5Hz,1H),5.04(d,J=1 .5Hz,1H),2.65(s,2H),2.10(s,3H),1.92–1.88(m,2H),1.77–1.68(m,6H). 13C NMR(126MHz, CDCl3)δ154.2,143.0,128.5,127.5,126.6,114.9,53.0,43.6,36.6,23.2,17.2.HRMS m / z(ESI)calcd for C 15 H 21 S(M+H) + 233.1358, found 233.1360.

[0130] Embodiment 20

[0131] The structural formula of the organic thioether compound prepared in this embodiment is as follows:

[0132]

[0133] The preparation method is as follows: under air conditions, α-cyclohexylstyrene sulfonium salt (1.0 mmol, 396.1 mg) t BuOK (1.5mmol, 168.3mg) was added to a 25ml reaction tube equipped with a magnetic stirrer, followed by the addition of solvent THF (5mL), and the reaction was stirred at room temperature for 4h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the crude product was separated by silica gel column chromatography, eluted with petroleum ether, and detected by TLC spot plate tracking. The eluate containing the target product was collected, the eluate of the target product was combined, and evaporated and concentrated to obtain the compound of the structure shown, with a yield of 62% (152.5mg). The substance is a colorless oily liquid.

[0134] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.29–7.23(m,5H),5.23(d,J=1.5Hz,1H),5.05(d,J=1 .5Hz,1H),2.63(s,2H),2.11(s,3H),1.76–1.72(m,2H),1.55–1.41(m,8H). 13 C NMR(126MHz, CDCl3)δ153.9,142.7,128.9,127.5,126.5,116.5,44.4,43.4,34.6,26.2,22.3,17.2.HRMS m / z(ESI)calcd for C 16 H 23 S(M+H) + 247.1515, found 247.1516.

[0135] Example 21: Effect of Base

[0136] Referring to Example 1, only potassium tert-butoxide was replaced with other bases shown in Table 1, and the other conditions remained unchanged. The results of the corresponding reactions are shown in Table 1.

[0137] Table 1 Effect of alkali on the preparation of organic sulfide compounds

[0138]

[0139]

[0140] Example 22: Effect of Solvent

[0141] Referring to Example 1, only the solvent tetrahydrofuran was replaced with other solvents shown in Table 2, and the other conditions remained unchanged. The results of the corresponding reactions are shown in Table 2.

[0142] Table 2 Effect of solvent selection on the preparation of organic sulfide compounds

[0143] Solvents Yield of organic sulfide compounds Tetrahydrofuran (Example 1) 93％ DCM 85％ 1,4-Dioxane 89％ Toluene 76％ DMSO <5％

[0144] Example 23: Reaction atmosphere expansion

[0145] Referring to Example 1, the atmosphere was replaced by oxygen and nitrogen respectively, and the other conditions remained unchanged. The results of the corresponding reactions are shown in Table 3.

[0146] Table 3 Effect of reaction atmosphere on organic sulfide compounds

[0147] Reaction atmosphere Yield of organic sulfide compounds Air (Example 1) 93％ oxygen 86％ Nitrogen 89％

[0148] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for synthesizing organic sulfide compounds by metal-free catalysis, characterized in that: Using the alkenyl sulfonium salt of formula 1 as a raw material, reacting in the presence of a base to obtain an organic sulfide compound of formula 2; Wherein R1 is selected from A substituted or unsubstituted aryl group, wherein the substitution is one to three, and the substituents are: halogen, C1-C4 alkyl, C1-C4 alkoxy, aryl; R2 and R3 are independently selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, or for "---" means there is a covalent bond or no covalent bond; Selected from or Z1 is CHR4, Z2 is C1-C4 alkyl, phenyl; R4 is H, C1-C4 alkyl; The reaction is carried out in an organic solvent, specifically any one or more of dichloromethane, 1,4-dioxane, tetrahydrofuran, and toluene; The base is sodium hydride, sodium tert-butoxide, sodium hydroxide or potassium tert-butoxide; The reaction temperature is 0°C to 60°C, and the reaction time is 3 to 12 hours.

2. The method according to claim 1, characterized in that The aryl group is a benzene ring or a naphthalene ring.

3. The method according to claim 1, characterized in that R1 is selected from:

4. The method according to claim 1, characterized in that: R2 and R3 are independently selected from hydrogen, methyl, phenyl, isopropyl, or for 5. The method according to claim 1, characterized in that The molar ratio of the alkenyl sulfonium salt represented by Formula I to the base is 1.0:1.0-2.

0.

6. The method according to claim 1, characterized in that The amount of the organic solvent added is 2 to 10 mL / mmol based on the amount of the alkenyl sulfonium salt represented by Formula I.

7. The method according to any one of claims 1 to 6, characterized in that: The reaction atmosphere is air, oxygen or nitrogen.

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