(2-Phenoxyphenyl)phenyl sulfide compounds and synthesis methods thereof

Abstract

The invention discloses a (2-phenoxyphenyl) phenyl sulfide compound and a synthesis method thereof, comprising the following steps: placing a 3-(phenylsulfinyl) tert-butyl propionate compound and a 2-(trimethylsilyl) phenyl trifluoromethanesulfonate compound in a 10 mL Shrek tube under an argon atmosphere, adding cesium fluoride and then adding a solvent, acetonitrile, and reacting at room temperature for 6 hours; after the reaction is completed, extraction, chromatographic separation, and drying are performed to obtain the target product. The present invention only uses cheap and readily available cesium fluoride as a fluorine source, and can efficiently obtain aryl sulfide compounds under mild conditions without the participation of a transition metal catalyst. The method provides a new approach for preparing various functionalized aryl sulfide compounds.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis and application, and specifically relates to a (2-phenoxyphenyl)phenyl sulfide compound and a synthesis method thereof. Background Art

[0002] Aryl sulfides are important structural units widely found in drugs and materials (J. Nat. Prod. 2007, 70, 439-442.; Chem. Rev. 2009, 109, 1141-1276.; J. Med. Chem. 2014, 57, 2832-2842.; Chem. Mater. 2014, 26, 724-744.). They can be used as important synthetic intermediates and various chiral ligands in organic synthesis. (J.Am.Chem.Soc.2003,125,3534-3543.;Chem.Rev.2007,107,5133-5209.;Angew.Chem.,Int.Ed.2016,55,2200-2204.;Org.Chem.Front.2015,2,973-977.;Angew.Chem.,Int.Ed.2015,54,8791-8794.). At present, there are many sulfur-containing drugs for treating various diseases on the market, such as antipsychotic drug chlorpromazine (Photochemistry and Photobiology,2009,85,895-900·) and antibacterial drug cefazolin (J.Org.Chem.1997,62,9099-9106). Therefore, the preparation of aryl sulfide compounds has received extensive attention from organic workers.

[0003] So far, there are many known methods for synthesizing aryl sulfide compounds, but most of them rely on the coupling reaction between aryl halides and sulfur-containing nucleophiles catalyzed by transition metal catalysts. Such reactions not only require high temperatures, but also require the participation of expensive transition metal catalysts (Angew. Chem., Int. Ed. 2008, 47, 2880-2883.; J. Am. Chem. Soc. 2008, 130, 12214-12215.; Chem. Commun. 2012, 48, 76-78.). Therefore, it is very necessary to develop a synthesis strategy for aryl sulfides without the participation of transition metals.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The purpose of the present invention is to provide a (2-phenoxyphenyl)phenyl sulfide compound and a synthesis method thereof, which is simple, easy to operate, low in cost and easy to purify. In the present invention, only cheap and readily available cesium fluoride is used as a fluorine source, and a method for synthesizing aryl sulfide compounds with mild conditions, simple operation and high efficiency is developed under the condition of no transition metal catalyst, and the method provides a new way to prepare a variety of functionalized aryl sulfide compounds.

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

[0007] A (2-phenoxyphenyl)phenyl sulfide compound, the general structural formula of which is:

[0008]

[0009] Where R 1 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; R 2 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.

[0010] The synthesis method of the (2-phenoxyphenyl)phenyl sulfide compound of the present invention comprises the following steps: under an argon atmosphere, adding tert-butyl 3-(phenylsulfinyl)propionate compound and phenyl 2-(trimethylsilyl)trifluoromethanesulfonate compound into a reaction tube, adding cesium fluoride, and finally adding a solvent, and reacting at room temperature for 6 hours; extracting after the reaction is completed, and after the extraction is complete, concentrating the organic phase by rotary evaporation, separating by chromatography, and drying to obtain the target product. The reaction equation is as follows:

[0011]

[0012] The general formula of the tert-butyl 3-(phenylsulfinyl) propionate compound is:

[0013]

[0014] The general structural formula of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate compounds is:

[0015]

[0016] Where R 1 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; R 2 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.

[0017] Furthermore, the molar ratio of the tert-butyl 3-(phenylsulfinyl) propionate compound to the 2-(trimethylsilyl) phenyl trifluoromethanesulfonate compound is 1:2.2.

[0018] Furthermore, the amount of cesium fluoride used is 6.6 times the amount of tert-butyl 3-(phenylsulfinyl)propionate compound.

[0019] Furthermore, the amount of the solvent acetonitrile is 1 mL, based on the amount of 0.1 mmol of tert-butyl 3-(phenylsulfinyl)propionate compound.

[0020] Furthermore, the extraction agent used in the extraction is ethyl acetate.

[0021] Furthermore, the eluent used in the chromatographic separation is ethyl acetate and petroleum ether in a volume ratio of 1:10.

[0022] Beneficial effects of the invention: The invention provides a simple and easy method for synthesizing (2-phenoxyphenyl)phenyl sulfide compounds. The method uses only cheap and readily available cesium fluoride as a fluorine source, and develops a method for synthesizing aryl sulfide compounds with mild conditions, simple operation, and high efficiency under the condition of no transition metal catalyst. The method provides a new way to prepare a variety of functionalized aryl sulfide compounds. DETAILED DESCRIPTION

[0023] The present invention is further described below in conjunction with specific examples. It should be understood that the following examples are only used to illustrate the present invention and are not used to limit the scope of the present invention, and those skilled in the art in this field can make some non-essential improvements and adjustments based on the content of the above invention.

[0024] Example 1

[0025] The structural formula of the compound (4-tolyl)(2-phenoxyphenyl) sulfide of this embodiment is:

[0026]

[0027] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(p-tolylsulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, concentration is performed under reduced pressure, and then chromatographic separation (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and drying is performed to obtain a white solid with a yield of 94%; 1 H NMR (600 MHz, CDCl 3)δ7.44(d,J=8.3Hz,2H),7.34–7.29(m,2H),7.08(t,J=7.6Hz,2H),6.96(dd,J=13.3,7.5Hz,3H),6.89(dd,J=14.7,8.7Hz,4H),3.81(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.2,153.9,138.1,133.5,130.3,130.2,129.9,129.8,129.5,127.3,124.3,123.1,119.4,118.2,21.2ppm.

[0028] Example 2

[0029] The structural formula of the compound (2-tolyl)(2-phenoxyphenyl) sulfide of this embodiment is:

[0030]

[0031] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(o-tolylsulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed using ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a yellow oil with a yield of 90%; 1 H NMR (600 MHz, CDCl 3 )δ7.40(d,J=7.1Hz,1H),7.34–7.29(m,2H),7.25(qd,J=8.0,7.5,1.9Hz,2H),7.15-7.19(m,1H),7.12 (td,J=7.7,1.7Hz,1H),7.08(t,J=7.4Hz,1H),7.00–6.95(m,3H),6.92-6.87(m,2H),2.36(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ158.1,154.0,141.3,134.5,131.9,130.7,129.8,129.7,128.9,128.5,127.2,126.8,124.3,123.1,119.5,118.2,20.6ppm.

[0032] Example 3

[0033] The structural formula of the compound (3-tolyl)(2-phenoxyphenyl) sulfide of this embodiment is:

[0034]

[0035] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and the mixture is reacted at room temperature for 6 hours; after the reaction is completed, the mixture is extracted with ethyl acetate, concentrated under reduced pressure, and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a yellow solid with a yield of 91%; 1 H NMR (600 MHz, CDCl 3 )δ7.31(dd,J=8.6,7.3Hz,2H),7.25(d,J=2.2Hz,1H),7.21(dd,J=4.8,1.6Hz,2H),7.18–7.12(m,2H),7.11–7.0 5(m,2H),7.01(td,J=7.6,1.4Hz,1H),6.94(dd,J=8.7,1.2Hz,2H),6.90(dd,J=8.1,1.3Hz,1H),2.31(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.2,154.5,139.1,133.4,133.2,131.4,129.7,129.1,128.8,128.5,127.8,124.2,123.2,22.8ppm.

[0036] Example 4

[0037] The structural formula of the compound (2,4-dimethylphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0038]

[0039] The preparation method is as follows: under an argon atmosphere, 28.2 mg (0.1 mmol) of tert-butyl 3-(2,4-xylylsulfinyl) propionate, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and the mixture is reacted at room temperature for 6 hours; after the reaction is completed, the mixture is extracted with ethyl acetate, concentrated under reduced pressure, and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a colorless oil with a yield of 92%; 1 H NMR (600 MHz, CDCl 3 )δ7.36(d,J=7.8Hz,1H),7.34–7.29(m,2H),7.11(s,1H),7.10–7.06(m,2H),7.02–6.97(m,3H),6.94(td ,J=7.6,1.4Hz,1H),6.89(dd,J=8.1,1.3Hz,1H),6.76(dd,J=7.9,1.6Hz,1H),2.33(d,J=5.8Hz,6H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.3,153.3,141.9,139.1,135.6,131.7,130.1,129.7,128.5,127.7,127.6,126.5,124.3,123.0,119.5,118.0,21.1,20.5ppm.

[0040] Example 5

[0041] The structural formula of the compound (2,6-dimethylphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0042]

[0043] The preparation method is as follows: under an argon atmosphere, 28.2 mg (0.1 mmol) of tert-butyl 3-(2,6-dimethylphenylsulfinyl) propionate, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a yellow oil with a yield of 82%; 1 H NMR (600 MHz, CDCl 3)δ7.37–7.30(m,2H),7.23(dd,J=8.4,6.5Hz,1H),7.18(d,J=7.5Hz,2H),7.09(t,J=7.4Hz ,1H),7.06–6.98(m,3H),6.93–6.86(m,2H),6.47(dd,J=7.8,1.6.Hz,1H),2.41(s,6H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.5,152.7,144.3,130.4,129.6,129.4,129.3,128.5,125.9,125.5,124.5,122.9,119.7,117.9,23.2ppm.

[0044] Example 6

[0045] The structural formula of the compound (4-ethylphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0046]

[0047] The preparation method is as follows: under an argon atmosphere, 28.2 mg (0.1 mmol) of tert-butyl 3-(4-ethylphenylsulfinyl) propionate compound, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, concentration is performed under reduced pressure, and then chromatographic separation (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and drying is performed to obtain a yellow oil with a yield of 90%; 1 H NMR (600 MHz, CDCl 3 )δ7.37(d,J=8.1Hz,2H),7.33–7.28(m,2H),7.17(d,J=7.9Hz,2H),7.15–7.10(m,1H),7.07(dd,J=15.1,7.7Hz,2H), 6.99(t,J=7.6Hz,1H),6.95(d,J=7.4Hz,2H),6.89(d,J=8.0Hz,1H),2.65(q,J=7.6Hz,2H),1.24(t,J=7.6Hz,3H)ppm. 13 C NMR (151 MHz, CDCl 3)δ157.2,154.0,144.4,133.5,130.5,129.8,129.74,129.66,128.9,127.4,124.2,123.1,119.4,118.2,28.6,15.4ppm.

[0048] Example 7

[0049] The structural formula of the compound (4-tert-butylphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0050]

[0051] The preparation method is as follows: under an argon atmosphere, 31.0 mg (0.1 mmol) of tert-butyl 3-(4-tert-butylphenylsulfinyl) propionate compound, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a colorless oil with a yield of 85%; 1 H NMR (600 MHz, CDCl 3 )δ7.39–7.33(m,4H),7.32–7.28(m,2H),7.16–7.11(m,1H),7.11–7.05(m,2H),7.02–6 .98(m,1H),6.94(dt,J=7.6,1.1Hz,2H),6.89(dd,J=8.1,1.3Hz,1H),1.31(s,9H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.2,154.2,151.2,133.0,130.7,129.7,129.6,129.57,127.5,126.4,124.2,123.1,119.4,118.2,34.6,31.3ppm.

[0052] Example 8

[0053] The structural formula of the compound (4-methoxyphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0054]

[0055] The preparation method is as follows: under an argon atmosphere, 28.4 mg (0.1 mmol) of tert-butyl 3-(4-methoxyphenylsulfinyl) propionate compound, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a yellow solid with a yield of 75%; 1 H NMR (600 MHz, CDCl 3 )δ7.44(d,J=9.0Hz,2H),7.35–7.27(m,2H),7.13–7.05(m,2H),7.02–6.94(m,3H),6.94–6.82(m,4H),3.81(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ160.1,157.2,153.1,136.3,131.2,129.7,128.9,126.7,124.3,123.1,122.6,119.3,118.1,115.1,55.4ppm.

[0056] Example 9

[0057] The structural formula of the compound (4-fluorophenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0058]

[0059] The preparation method is as follows: under an argon atmosphere, 27.2 mg (0.1 mmol) of tert-butyl 3-(4-fluorophenylsulfinyl) propionate compound, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a white solid with a yield of 87%; 1 H NMR (600 MHz, CDCl 3)δ7.45–7.39(m,2H),7.34–7.28(m,2H),7.18–7.14(m,1H),7.11–7.06(m,2H), 7.06–6.99(m,3H),6.93(dd,J=8.7,1.2Hz,2H),6.90(dd,J=8.1,1.3Hz,1H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ163.5,161.8,157.0,154.3,135.2,135.1,130.9,129.7,129.0,128.7,127.9,124.3,123.3,119.4,118.2,116.5,116.4ppm.

[0060] Example 10

[0061] The structural formula of the compound (4-chlorophenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0062]

[0063] The preparation method is as follows: under an argon atmosphere, 28.8 mg (0.1 mmol) of tert-butyl 3-(4-chlorophenylsulfinyl) propionate, 65.6 mg (0.22 mmol) of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a white solid with a yield of 74%; 1 H NMR (600 MHz, CDCl 3 )δ7.34–7.28(m,4H),7.28–7.24(m,2H),7.21(t,J=7.5Hz,2H),7.09(t,J=7.4Hz,1H),7.05(td,J=7.6,1.3Hz,1H),6.95–6.87(m,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ156.9,155.2,133.4,133.0,132.4,129.7,129.3,128.7,127.3,124.3,123.4,119.5,118.3ppm.

[0064] Embodiment 11

[0065] The structural formula of the compound (4-bromophenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0066]

[0067] The preparation method is as follows: under an argon atmosphere, 33.2 mg (0.1 mmol) of tert-butyl 3-(4-bromosulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a white solid with a yield of 74%; 1 H NMR (600 MHz, CDCl 3 )δ7.41(d,J=8.4Hz,2H),7.34–7.28(m,2H),7.29-7.19(m,4H),7.09(t,J=7.4Hz,1H),7.05(td,J=7.6,1.3Hz,1H),6.94–

[0068] 6.88 (m, 3H) ppm. 13 C NMR (151 MHz, CDCl 3 )δ156.9,155.3,133.9,133.1,132.6,132.2,129.7,128.9,127.0,124.3,123.4,121.3,119.5,118.3ppm.

[0069] Example 12

[0070] The structural formula of the compound (4-trifluoromethylphenyl) (2-phenoxyphenyl) sulfide of this embodiment is:

[0071]

[0072] The preparation method is as follows: under an argon atmosphere, 32.2 mg (0.1 mmol) of tert-butyl 3-(4-trifluoromethylphenylsulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a colorless oil with a yield of 66%;1 H NMR (600 MHz, CDCl 3 )δ7.50–7.44(m,3H),7.34–7.27(m,5H),7.14–7.07(m,2H),6.95(dd,J=8.2,1.3Hz,1H),6.87(d,J=7.5Hz,2H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ145.3,140.6,135.2,135.0,134.8,134.6,133.8,129.5,128.2,127.9,126.48,126.46,126.43,126.41,125.8,124.0,122.2,120.4ppm.

[0073] Example 13

[0074] The structural formula of the compound (2-phenoxyphenyl)naphthyl sulfide of this embodiment is:

[0075]

[0076] The preparation method is as follows: under an argon atmosphere, 30.4 mg (0.1 mmol) of tert-butyl 3-(naphthylsulfinyl) propionate, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are sequentially added into a 10 mL Shrek tube, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, concentration is performed under reduced pressure, and then chromatographic separation is performed (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and drying is performed to obtain a white solid with a yield of 85%; 1 HNMR (600MHz, CDCl 3 )δ7.91(s,1H),7.78(d,J=8.5Hz,1H),7.76–7.72(m,1H),7.50–7.44(m,3H),7.33–7.27(m,2H),7.1 9(td,J=7.3,1.5Hz,2H),7.10–7.05(m,1H),7.01(td,J=7.6,1.3Hz,1H),6.94(t,J=8.3Hz,3H)ppm. 13 C NMR (151 MHz, CDCl 3)δ157.1,154.7,133.9,132.5,131.7,131.4,131.2,129.7,129.6,128.9, 128.4,128.1,127.7,127.5,126.5,126.3,124.3,123.2,119.5,118.3ppm.

[0077] Embodiment 14

[0078] The structural formula of the compound (2-phenoxyphenyl)thienyl sulfide of this embodiment is:

[0079]

[0080] The preparation method is as follows: under an argon atmosphere, 26.0 mg (0.1 mmol) of tert-butyl 3-(thienylsulfinyl) propionate compound, 65.6 mg (0.22 mmol) of phenyl 2-(trimethylsilyl) trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a white solid with a yield of 70%; 1 H NMR (600 MHz, CDCl 3 )δ7.50(d,J=5.4Hz,1H),7.34(t,J=7.7Hz,2H),7.30(d,J=3.6Hz,1H),7.13–7.07(m ,3H),7.00(dd,J=13.3,7.6Hz,3H),6.95(d,J=7.8Hz,1H),6.86(d,J=8.1Hz,1H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ157.1,152.9,136.9,131.7,1310,129.8,129.6,128.10,128.05,127.0,124.4,123.3,119.0,118.3ppm.

[0081] Embodiment 15

[0082] The structural formula of the compound (2-methoxy-6-(3-methoxyphenoxy)phenyl)tolyl sulfide of this embodiment is:

[0083]

[0084] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(p-tolylsulfinyl) propionate, 72.2 mg (0.22 mmol) of 6-methoxy-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a yellow oily substance with a yield of 53%; 1 H NMR (600 MHz, CDCl 3 )δ7.29(t,J=8.3Hz,1H),7.14(t,J=8.1Hz,1H),7.07(d,J=8.2Hz,2H),6.97(d,J=8.0Hz,2H),6.74(dd,J=8.4,1. 1Hz,1H),6.63–6.58(m,2H),6.45–6.41(m,1H),6.39(t,J=2.4Hz,1H),3.85(s,3H),3.72(s,3H),2.25(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ161.5,160.8,159.0,158.4,135.2,133.7,130.6,129.9,129.3,128.2,113.5,112.4,110.7,109.0,106.8,104.6,56.4,55.3,20.9ppm.

[0085] Example 16

[0086] The structural formula of the compound (2-fluoro-6-(3-fluorophenoxy)phenyl)tolyl sulfide of this embodiment is:

[0087]

[0088] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 69.5 mg (0.22 mmol) of 6-fluoro-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, concentration is performed under reduced pressure, and then chromatographic separation (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and drying is performed to obtain a colorless oily substance with a yield of 66%; 1H NMR (600 MHz, CDCl 3 )δ7.30(td,J=8.3,6.2Hz,1H),7.25–7.19(m,1H),7.15(d,J=7.9Hz,2H),7.01(d,J=7.9Hz,2H),6.96 (t,J=8.2Hz,1H),6.83–6.74(m,2H),6.63(d,J=8.3Hz,1H),6.52(d,J=10.1Hz,1H),2.27(s,3H)ppm. 13 CNMR (151MHz, CDCl 3 )δ164.6,164.3,162.9,162.6,158.34,158.26,158.99,157.97,136.6,131.8,130.6,130.53,130.47,130.4,12 9.8,129.6,115.82,115.80,115.2,115.0,113.73,113.71,112.0,111.8,110.3,110.2,106.0,105.8,21.0ppm.

[0089] Embodiment 17

[0090] The structural formula of the compound (2-chloro-6-(3-fluorophenoxy)phenyl)tolyl sulfide of this embodiment is:

[0091]

[0092] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 73.0 mg (0.22 mmol) of 6-chloro-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a colorless oily substance with a yield of 52%; 1 H NMR (600 MHz, CDCl 3 )δ7.33(d,J=8.1Hz,1H),7.27–7.24(m,1H),7.17(t,J=7.9Hz,1H),7.10(d,J=7.9Hz, 2H),7.05–6.96(m,3H),6.87(d,J=8.2Hz,1H),6.68(d,J=8.4Hz,2H),2.27(s,3H)ppm. 13C NMR (151 MHz, CDCl 3 )δ158.4,157.7,140.8,136.4,135.0,132.1,130.4,130.3,129.6,129.4,126.4,126.0,123.4,118.8,118.4,116.3,21.0ppm.

[0093] Embodiment 18

[0094] The structural formula of the compound (3,4-dimethyl-6-(3,4-dimethylphenoxy)phenyl)tolyl sulfide of this embodiment is:

[0095]

[0096] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 71.7 mg (0.22 mmol) of 4,5-dimethyl-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a light yellow oily substance with a yield of 53%; 1 H NMR (600 MHz, CDCl 3 )δ7.28–7.24(m,2H),7.09(d,J=7.9Hz,2H),7.02(d,J=8.2Hz,1H),6.99(s,1H),6.70(s,1H),6.68(d,J =2.6Hz,1H),6.63(dd,J=8.2,2.7Hz,1H),2.32(s,3H),2.20(d,J=5.9Hz,6H),2.15(d,J=7.3Hz,6H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ155.6,153.3,137.9,137.3,136.9,133.3,132.5,131.7,131.6,130.8,13 0.4,129.8,124.5,120.9,119.2,115.1,21.1,19.9,19.6,19.01,18.97ppm.

[0097] Embodiment 19

[0098] The structural formula of the compound (3,4-difluoro-6-(3,4-difluorophenoxy)phenyl)tolyl sulfide of this embodiment is:

[0099]

[0100] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 73.5 mg (0.22 mmol) of 4,5-difluoro-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, and the mixture is concentrated under reduced pressure and then chromatographically separated (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and dried to obtain a light yellow oily substance with a yield of 43%; 1 H NMR (600 MHz, CDCl 3 )δ7.30(td,J=8.3,6.2Hz,1H),7.25–7.19(m,1H),7.15(d,J=7.9Hz,2H),7.01(d,J=7.9Hz,2H),6.96 (t,J=8.2Hz,1H),6.83–6.74(m,2H),6.63(d,J=8.3Hz,1H),6.52(d,J=10.1Hz,1H),2.27(s,3H)ppm. 13 C NMR (151 MHz, CDCl 3 )δ164.6,164.3,162.9,162.6,158.34,158.26,157.99,157.97,136.6,131.8,130.6,130.53,130.47,130.4,12 9.8,129.6,115.82,115.80,115.2,115.0,113.73,113.71,112.0,111.8,110.3,110.2,106.0,105.8,21.0ppm.

[0101] Embodiment 20

[0102] The structural formula of the compound 5-benzo[1,3]dioxolane-5-yloxy)-6-p-tolylbenzo[1,3]dioxolane in this embodiment is:

[0103]

[0104] The preparation method is as follows: under an argon atmosphere, 26.8 mg (0.1 mmol) of tert-butyl 3-(3-tolylsulfinyl) propionate, 75.2 mg (0.22 mmol) of 6-(trimethylsilyl)benzo[1,3]dioxolan-5-yl trifluoromethanesulfonate, 100.3 mg (0.66 mmol) of cesium fluoride, and 1 mL of acetonitrile are added to a 10 mL Shrek tube in sequence, and reacted at room temperature for 6 hours; after the reaction is completed, extraction is performed with ethyl acetate, concentration is performed under reduced pressure, and then chromatography is performed (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio 1:10), and drying is performed to obtain a light yellow oily substance with a yield of 43%; 1 H NMR (600 MHz, CDCl 3 )δ7.24(d,J=8.1Hz,2H),7.10(d,J=7.8Hz,2H),6.69(d,J=7.3Hz,2H),6.49(s,1H),6.4 5(d,J=2.4Hz,1H),6.34(dd,J=8.4,2.5Hz,1H),5.93(d,J=2.7Hz,4H),2.32(s,3H)ppm. 13 CNMR (151MHz, CDCl 3 )δ152.6,150.4,148.3,147.9,144.2,143.3,137.2,131.6,131.4,129.9,119.4,111.8,109.9,108.1,101.9,101.8,101.4,100.6,21.1ppm.

[0105] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A method for synthesizing (2-phenoxyphenyl)phenyl sulfide compounds, Features The method comprises the following steps: adding tert-butyl 3-(phenylsulfinyl) propionate compounds and phenyl 2-(trimethylsilyl) trifluoromethanesulfonate compounds into a reaction tube under an argon atmosphere, adding cesium fluoride, and finally adding a solvent to react; after the reaction is completed, extracting, chromatographic separation, and drying to obtain a target product, wherein the solvent is acetonitrile, the reaction temperature is room temperature, and the reaction time is 6 hours; The reaction equation is as follows: ； Where R 1 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; R 2 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.

2. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: The general structural formula of the tert-butyl 3-(phenylsulfinyl) propionate compound is: ； The general structural formula of the 2-(trimethylsilyl)phenyl trifluoromethanesulfonate compound is: ； Where R 1 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; R 2 is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.

3. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: The molar ratio of the 3-(phenylsulfinyl)propionic acid tert-butyl ester compound to the 2-(trimethylsilyl)trifluoromethanesulfonic acid phenyl ester compound is 1:2.

2.

4. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: The molar ratio of the cesium fluoride to the tert-butyl 3-(phenylsulfinyl) propionate compound is 6.6:

1.

5. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: Based on 0.1 mmol of tert-butyl 3-(phenylsulfinyl)propionate, the amount of the solvent used is 1 mL.

6. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: The extraction agent used in the extraction is ethyl acetate.

7. The method for synthesizing the (2-phenoxyphenyl)phenyl sulfide compound according to claim 1, Features: The eluent used in the chromatographic separation was ethyl acetate and petroleum ether in a volume ratio of 1:10.

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