Preparation method of a thiazolidine-4-thione derivative

Abstract

The present invention discloses a preparation method of thiazolidine-4-thione derivatives, which comprises the following steps: (1) mixing an isothiocyanate or its derivative, a sulfur ylide, an additive and an organic solvent, and reacting at 20-90 °C for 12-48 h under an air atmosphere; (2) diluting the material obtained in step (1) with ethyl acetate and washing with water, and separating to obtain an organic phase; (3) subjecting the above organic phase to drying, filtration, concentration and column chromatography or thin-layer chromatography in sequence to obtain thiazolidine-4-thione derivatives. The present invention can construct tetra-substituted thiazolidine-4-thione derivatives, can efficiently synthesize thiazolidine-4-thione derivatives containing trifluoromethyl, the raw materials used are easily available, the yield is high, the reaction conditions are mild, the reaction time is short, the substrate range is wide, the reaction specificity is strong, and the post-treatment is simple.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of thiazolidine-4-thione derivatives. Background Art

[0002] Thiazolidine-4-thione is an important nitrogen-containing heterocyclic compound. A series of thiazolidine-4-thiones and their derivatives can be extracted from living cells, and they play important roles in organisms and drugs. Therefore, various biological activities have been observed in drugs and natural products containing the thiazolidine-4-thione structure. Such compounds and their derivatives play important roles in fields such as protein inhibitors, antihypertensive drugs, and insecticidal drugs. In the field of pesticides, the antifungal effects of thiazolidine compounds have also been widely studied. In addition, introducing a trifluoromethyl group into the bioactive small molecule mother nucleus can change the properties of the compound, such as selectivity and lipophilicity. Moreover, the synthesis of trifluoromethyl-containing thiazolidine compounds is attractive for their potential applications in drug screening. Therefore, the effective synthesis and functionalization of thiazolidine-4-thione compounds have always been a research hotspot at home and abroad. Summary of the Invention

[0003] The purpose of the present invention is to provide a preparation method of thiazolidine-4-thione derivatives.

[0004] The reaction formula of the present invention is as follows:

[0005]

[0006] The technical solution of the present invention is as follows:

[0007] A preparation method of thiazolidine-4-thione derivatives, comprising the following steps:

[0008] (1) Mix an isothiocyanate or its derivative, a sulfur ylide, an additive, and an organic solvent, and react at 20 - 90 °C for 12 - 48 h under an air atmosphere;

[0009] (2) Dilute the material obtained in step (1) with ethyl acetate and wash it with water, and then separate to obtain an organic phase;

[0010] (3) Subject the above organic phase to drying, filtration, concentration, and column chromatography or thin-layer chromatography in sequence to obtain thiazolidine-4-thione derivatives;

[0011] The structural formula of the above isothiocyanate or its derivative is wherein, R is hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, benzyloxy, N,N-dialkyl, or S-alkyl;

[0012] The structural formula of the above sulfur ylide is wherein R1 is hydrogen, alkyl, alkoxy, trifluoromethyl, halogen, nitro or cyano, R 2 is hydrogen, halogen, trifluoromethyl or pentafluoroethyl.

[0013] In a preferred embodiment of the present invention, the halogen is fluorine, chlorine or bromine.

[0014] In a preferred embodiment of the present invention, the sulfonium ylide is selected from (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-fluorophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-chlorophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-trifluoromethylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-nitrophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-bromophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(3-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(3-trifluoromethylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1-difluoro-N-phenylpropan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-3,3,4,4,4-pentafluoro-N-phenylbutan-2-imine and (E)-3-(dimethyl(oxo)-λ6 -sulfinyl)-3,3,4,4,5,5,5-heptafluoro-N-phenylpentan-2-imine.

[0015] In a preferred embodiment of the present invention, the additive is selected from sodium trifluoromethanesulfonate, potassium trifluoromethanesulfonate, sodium p-toluenesulfonate, sodium methylsulfonate, sodium sulfate, sodium bisulfite, sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium thiosulfate pentahydrate, sodium dithionite, sodium persulfate, sodium amidosulfonate, sodium formate, sodium difluorochloroacetate, sodium chloride, sodium bromide, sodium iodide, sodium periodate, sodium trifluoromethylsulfinate, sodium lignosulfonate, sodium benzenesulfinate, sodium nitrite and sodium trimethylacetate.

[0016] More preferably, the additive is sodium trifluoromethylsulfinate.

[0017] In a preferred embodiment of the present invention, the organic solvent is ethanol, tert-butanol, ether, ethylene glycol dimethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, 1,2-dichloroethane, toluene, 1,4-dioxane, tetrahydrofuran, hexafluoroisopropanol, methyl tert-butyl ether or acetonitrile.

[0018] More preferably, the organic solvent is methyl tert-butyl ether.

[0019] In a preferred embodiment of the present invention, the isothiocyanate or its derivative is phenyl isothiocyanate, 4-methoxyphenyl isothiocyanate, 4-methylphenyl isothiocyanate, 4-tert-butylphenyl isothiocyanate, 4-fluorophenyl isothiocyanate, 2-fluorophenyl isothiocyanate, 2-methoxyphenyl isothiocyanate or 3-methoxyphenyl isothiocyanate.

[0020] In a preferred embodiment of the present invention, the organic solvent is methyl tert-butyl ether, the additive is sodium trifluoromethylsulfinate, and the organic solvent is methyl tert-butyl ether.

[0021] In a preferred embodiment of the present invention, the molar ratio of the isothiocyanate or its derivative, the sulfur ylide and the additive is 1-4:1:0-4, and for every 0.01 mmol of the sulfur ylide, 0.1-2 mL of the organic solvent is corresponding.

[0022] More preferably, the molar ratio of the isothiocyanate or its derivative, the sulfur ylide and the additive is 3:1:1-3, and for every 0.1 mmol of the sulfur ylide, 1.5 mL of the organic solvent is corresponding.

[0023] The beneficial effects of the present invention are:

[0024] 1. The present invention can construct tetrasubstituted thiazolidine-4-thione derivatives and can efficiently synthesize thiazolidine-4-thione derivatives containing trifluoromethyl groups.

[0025] 2. The raw materials used in the present invention are readily available, with high yields, mild reaction conditions, short reaction times, a wide substrate range, strong reaction specificity, and simple post-treatment. Specific Embodiments

[0026] The technical solutions of the present invention are further illustrated and described below through specific embodiments.

[0027] Example 1

[0028] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-methoxyphenyl)amino)ethylidene)thiazolidine-4-thione

[0029]

[0030] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methoxyphenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate, and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube. Place it in an oil bath at 50 °C under an air atmosphere and react for 48 h; cool to room temperature. Dilute the reaction solution with ethyl acetate, wash it three times with water, dry the organic phase with anhydrous Na 2 SO 4 Filter, concentrate, and purify by column chromatography to obtain 33.8 mg of the target product with a yield of 70%.

[0031] The nuclear magnetic resonance and high-resolution mass spectrometry characterizations of the target product are as follows:

[0032] 1 H NMR(500MHz,Chloroform-d)δ13.86(s,1H),7.61–7.56(m,2H),7.53–7.48(m,1H),7.38–7.30(m,4H),7.11(dd,J=8.3,5.0Hz,3H),6.96(d,J=7.3Hz,2H),6.91–6.86(m,2H),3.80(s,3H).

[0033] 1313C NMR (126 MHz, Chloroform-d) δ 187.2, 158.7, 149.2, 141.0 (q, J = 32.1 Hz), 137.3, 130.4, 129.7, 129.4, 129.3, 128.9, 126.6, 124.6, 120.8, 120.8 (q, J = 281.7 Hz), 114.3, 103.1, 55.5.

[0034] 19 19F NMR (471 MHz, Chloroform-d) δ -58.9.

[0035] HRMS (ESI-TOF) m / z: calcd for C 24 H 18 F 3 N 3 OS 2 + : 486.0917 (M+H) + , found: 486.0917.

[0036] Example 2

[0037] (2Z,5E)-3-Phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-methylphenyl)amino)ethylidene)thiazolidine-4-thione Preparation

[0038]

[0039] 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methylphenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, placed in an oil bath at 50 °C under an air atmosphere, and reacted for 48 h; cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 , filtered, concentrated, and purified by column chromatography to obtain 30.5 mg of the target product with a yield of 65%.

[0040] The NMR and high-resolution mass spectrometry characterization of the target product are as follows:

[0041] 11H NMR (500 MHz, Chloroform-d) δ 13.83 (s, 1H), 7.58 (dd, J = 8.4, 7.3 Hz, 2H), 7.52–7.47 (m, 1H), 7.39–7.31 (m, 4H), 7.16 (d, J = 8.1 Hz, 2H), 7.11 (tt, J = 7.5, 1.2 Hz, 1H), 7.06 (d, J = 8.1 Hz, 2H), 7.00–6.92 (m, 2H), 2.35 (s, 3H).

[0042] 13 13C NMR (126 MHz, Chloroform-d) δ 187.4, 155.4, 149.2, 140.5 (q, J = 32.4 Hz), 137.3, 137.0, 135.2, 129.8, 129.7, 129.4, 129.3, 128.9, 124.8, 124.6, 120.8 (q, J = 281.6 Hz), 120.8, 103.7, 21.0.

[0043] 19F NMR (471 MHz, Chloroform-d) δ -59.0.

[0044] HRMS (ESI-TOF) m / z: calcd for C 24 H 18 F 3 N 3 S 2 + : 470.0967 (M + H) + , found: 470.0967.

[0045] Example 3

[0046] (2Z,5E)-3-Phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-fluorophenyl)amino)ethylidene)thiazolidine-4-thione Preparation

[0047]

[0048] 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-fluorophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, placed in an oil bath at 50 °C under an air atmosphere, and reacted for 48 h; cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried over anhydrous Na 2 SO4 It was dried, filtered, concentrated, and purified by column chromatography to obtain 33 mg of the target product with a yield of 70%.

[0049] The nuclear magnetic resonance and high-resolution mass spectrometry characterization of the target product are as follows:

[0050] 1 H NMR(500MHz,Chloroform-d)δ13.72(s,1H),7.59(dd,J=8.4,7.1Hz,2H),7.53–7.48(m,1H),7.39–7.30(m,4H),7.17–7.10(m,3H),7.08–7.02(m,2H),6.99–6.93(m,2H).

[0051] 13 C NMR(126MHz,Chloroform-d)δ187.8,162.4,160.4,155.1,149.1,140.2(q,J=32.5Hz),137.2,133.9,129.7,129.4(d,J=9.5Hz),128.8,126.9(d,J=8.6Hz),124.7,120.8(q,J=281.4Hz),120.7,116.1(d,J=23.0Hz),104.4.

[0052] 19 F NMR(471MHz,Chloroform-d)δ-58.9,-114.3.

[0053] HRMS(ESI-TOF)m / z:calcd for C 23 H 15 F 4 N 3 S 2 + :474.0717(M+H) + ,found:474.0717.

[0054] Example 4

[0055] (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-chlorophenyl)amino)ethylidene)thiazolidine-4-thione Preparation

[0056]

[0057] 0.3 mmol of phenyl isothiocyanate, ((E)-3-(dimethyl(oxo)-λ 60.1 mmol of (1 - sulfinyl)-1,1,1 - trifluoro - N-(4 - chlorophenyl)propan - 2 - imine, 0.3 mmol of sodium trifluoromethanesulfonate and 1.5 mL of methyl tert - butyl ether were added to a 15 - mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 35 mg of the target product with a yield of 72%.

[0058] The NMR and high - resolution mass spectrometry characterization of the target product are as follows:

[0059] 1 H NMR (500 MHz, Chloroform - d) δ 13.63 (s, 1H), 7.57 (t, J = 7.8 Hz, 2H), 7.51–7.47 (m, 1H), 7.37–7.31 (m, 5H), 7.30 (s, 1H), 7.11 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 8.3 Hz, 2H), 6.99–6.94 (m, 2H).

[0060] 13 C NMR (126 MHz, Chloroform - d) δ 188.0, 154.9, 148.9, 139.4 (q, J = 32.6 Hz), 137.2, 136.7, 132.5, 129.7, 129.4, 129.3, 128.8, 125.9, 124.8, 120.8 (q, J = 280.6, 280.2 Hz), 120.7, 105.5.

[0061] 19 F NMR (471 MHz, Chloroform - d) δ - 59.11.

[0062] HRMS (ESI - TOF) m / z: calcd for C 23 H 15 F 3 N 3 S 2 Cl + : 490.0421 (M + H) + , found: 490.0421.

[0063] Example 5

[0064] (2Z,5E)-3 - phenyl - 2-(phenylimino)-5-(2,2,2 - trifluoromethyl - 1 - ((4 - bromophenyl)amino)ethylidene)thiazolidine - 4 - thione Preparation

[0065]

[0066] 0.3 mmol of phenyl isothiocyanate, ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine 0.1 mmol, sodium trifluoromethanesulfinate 0.3 mmol and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the tube was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 and filtered, concentrated, and purified by column chromatography to obtain 49 mg of the target product with a yield of 91%.

[0067] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0068] 1 H NMR (500 MHz, Chloroform-d) δ 13.59 (s, 1H), 7.60–7.55 (m, 2H), 7.50 (dd, J = 7.9, 1.8 Hz, 1H), 7.47 (dd, J = 9.0, 2.5 Hz, 2H), 7.37–7.31 (m, 4H), 7.12 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.99–6.92 (m, 2H).

[0069] 13 C NMR (126 MHz, Chloroform-d) δ 188.1, 155.0, 149.0, 139.3 (q, J = 32.7 Hz), 137.3, 137.2, 132.4, 129.8, 129.5, 129.4, 128.8, 126.2, 124.8, 120.8 (q, J = 280.8 Hz), 120.7, 120.3, 105.7.

[0070] 19 F NMR (471 MHz, Chloroform-d) δ -59.2.

[0071] HRMS (ESI-TOF) m / z: calcd for C 23 H 15 F 3 N 3 S 2 Br + : 533.9916 (M+H) +,found:533.9915.

[0072] Example 6

[0073] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-trifluoromethylphenyl)amino)ethylidene)thiazolidine-4-thione

[0074]

[0075] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-trifluoromethylphenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube. Place it in an oil bath at 50 °C under an air atmosphere and react for 48 h; cool to room temperature. Dilute the reaction solution with ethyl acetate, wash it three times with water, dry the organic phase with anhydrous Na 2 SO 4 dry, filter, concentrate, and purify by column chromatography to obtain 36.7 mg of the target product with a yield of 70%.

[0076] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0077] 1 H NMR(500MHz,Chloroform-d)δ13.46(s,1H),7.63–7.56(m,4H),7.51(dd,J=8.4,6.5Hz,1H),7.34(t,J=8.0Hz,4H),7.22(d,J=8.1Hz,2H),7.13(t,J=7.3Hz,1H),6.96(d,J=7.5Hz,2H).

[0078] 13 C NMR(126MHz,Chloroform-d)δ188.6,154.6,148.8,141.8,138.3(q,J=33.2Hz),137.1,129.8,129.6,129.4,128.7,128.2(q,J=32.9Hz),126.5(q,J=3.8Hz),124.9,123.9,123.8(q,J=272.0Hz),120.8(q,J=281.0Hz),120.6,107.8.

[0079] 19 F NMR(471MHz,Chloroform-d)δ-59.6,-62.3.

[0080] HRMS(ESI-TOF) m / z: calculated for C 24 H 15 F 6 N 3 S 2 + : 524.0685 (M + H) + , found: 524.0685. Example 7

[0081] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((4-nitrophenyl)amino)ethylidene)thiazolidine-4-thione

[0082]

[0083] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-nitrophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube, place it in an oil bath at 50 °C under an air atmosphere, and react for 48 h; cool to room temperature, dilute the reaction solution with ethyl acetate, wash it three times with water, dry the organic phase with anhydrous Na 2 SO 4 dry, filter, concentrate, and purify by column chromatography to obtain 29 mg of the target product with a yield of 58%.

[0084] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0085] 1 H NMR (500 MHz, Chloroform-d) δ 13.12 (s, 1H), 8.27–8.19 (m, 2H), 7.59 (dd, J = 8.4, 6.9 Hz, 2H), 7.54–7.50 (m, 1H), 7.38–7.33 (m, 4H), 7.21–7.13 (m, 3H), 7.00–6.93 (m, 2H).

[0086] 13 C NMR (126 MHz, Chloroform-d) δ 189.2, 148.5, 145.1, 144.7, 136.9, 136.3 (q, J = 33.7 Hz), 129.9, 129.7, 129.5, 128.6, 126.3, 125.2, 125.1, 122.5, 120.5, 112.2 (q, J = 275.6 Hz).

[0087] 19 F NMR (471 MHz, Chloroform-d) δ -60.15.

[0088] HRMS (ESI-TOF) m / z: calcd for C 23 H 15 F 3 N 4 O 2 S 2 + : 501.0662 (M + H) + , found: 501.0663.

[0089] Example 8

[0090] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((2-methoxyphenyl)amino)ethylidene)thiazolidine-4-thione

[0091]

[0092] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-methoxyphenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube, place it in an oil bath at 50 °C under an air atmosphere, and react for 48 h; cool to room temperature, dilute the reaction solution with ethyl acetate, wash it three times with water, dry the organic phase with anhydrous Na 2 SO 4 dry, filter, concentrate, and purify by column chromatography to obtain 37.4 mg of the target product with a yield of 77%.

[0093] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0094] 1 H NMR (500 MHz, Chloroform-d) δ 13.62 (s, 1H), 7.57 (t, J = 7.7 Hz, 2H), 7.50–7.46 (m, 1H), 7.37 (dd, J = 8.4, 1.2 Hz, 2H), 7.32 (t, J = 7.9 Hz, 2H), 7.24–7.20 (m, 1H), 7.11 (q, J = 7.1 Hz, 2H), 6.97 (d, J = 7.4 Hz, 2H), 6.95–6.89 (m, 2H), 3.82 (s, 3H).

[0095] 13 C NMR (126 MHz, Chloroform-d) δ 187.1, 155.5 (q, J=2.9 Hz), 153.4, 149.3, 141.4 (q, J=32.8 Hz), 137.4, 129.6, 129.3, 128.9, 128.0, 127.0, 125.8, 124.5, 120.8, 120.7 (q, J=281.6 Hz), 120.5, 111.2, 103.7, 55.7.

[0096] 19 F NMR (471 MHz, Chloroform-d) δ -61.48.

[0097] HRMS (ESI-TOF) m / z: calcd for C 24 H 18 F 3 N 3 OS 2 + : 486.0917 (M+H) + , found: 486.0917.

[0098] Example 9

[0099] (2Z,5E)-3-Phenyl-2-(phenylimino)-5-(2,2,2-trifluoromethyl-1-((2-bromophenyl)amino)ethylidene)thiazolidine-4-thione Preparation

[0100]

[0101] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube, place it in an oil bath at 50 °C under an air atmosphere, and react for 48 h; cool to room temperature, dilute the reaction solution with ethyl acetate, wash it three times with water, dry the organic phase with anhydrous Na 2 SO 4 dry, filter, concentrate, and purify by column chromatography to obtain 41 mg of the target product with a yield of 75%.

[0102] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0103] 11H NMR (500 MHz, Chloroform-d) δ 13.53 (s, 1H), 7.62 (dd, J = 8.0, 1.4 Hz, 1H), 7.58 (t, J = 7.7 Hz, 2H), 7.52–7.47 (m, 1H), 7.40–7.32 (m, 4H), 7.29 (td, J = 7.7, 1.4 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 7.12 (td, J = 7.6, 1.5 Hz, 2H), 6.96 (dd, J = 7.9, 1.5 Hz, 2H).

[0104] 13 13C NMR (126 MHz, Chloroform-d) δ 188.4, 155.0, 149.0, 139.1 (q J = 32.6 Hz), 137.4, 137.2, 133.2, 129.7, 129.4, 129.4, 128.8, 128.1, 128.0, 126.8 (q, J = 2.5 Hz), 124.8, 120.7 (q, J = 281.3 Hz), 120.7, 119.6, 106.3.

[0105] 19 19F NMR (471 MHz, Chloroform-d) δ -59.98.

[0106] HRMS (ESI-TOF) m / z: calcd for C 23 H 15 F 3 N 3 S 2 Br + : 533.9916 (M + H) + , found: 533.9916.

[0107] Example 10

[0108] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((3-methoxyphenyl)amino)ethylidene)thiazolidine-4-thione

[0109]

[0110] 0.3 mmol of phenyl isothiocyanate, ((E)-3-(dimethyl(oxo)-λ 60.1 mmol of (1 - sulfinyl)-1,1,1 - trifluoro - N-(3 - methoxyphenyl)propan - 2 - imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert - butyl ether were added to a 15 - mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried over anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 35 mg of the target product with a yield of 72%.

[0111] The NMR and high - resolution mass spectrometry characterization of the target product are as follows:

[0112] 1 H NMR(500 MHz, Chloroform - d)δ13.70(s, 1H), 7.58(dd, J = 8.3, 7.1 Hz, 2H), 7.52–7.47(m, 1H), 7.38–7.31(m, 4H), 7.25(s, 1H), 7.12(tt, J = 7.4, 1.2 Hz, 1H), 6.98–6.94(m, 2H), 6.81(dd, J = 8.3, 2.3 Hz, 1H), 6.75(d, J = 7.9 Hz, 1H), 6.70(d, J = 2.3 Hz, 1H), 3.79(s, 3H).

[0113] 13 C NMR(126 MHz, Chloroform - d)δ187.7, 160.2, 155.2, 149.1, 139.9(q, J = 32.7 Hz), 139.2, 137.3, 129.9, 129.7, 129.4, 129.4, 128.8, 124.7, 120.8(q, J = 281.1 Hz), 120.7, 117.0, 112.6, 110.3, 104.9, 55.4.

[0114] 19 F NMR(471 MHz, Chloroform - d)δ - 59.24.

[0115] HRMS(ESI - TOF)m / z: calcd for C 24 H 18 F 3 N 3 OS 2 + : 486.0917(M + H) + , found: 486.0917.

[0116] Example 11

[0117] Preparation of (2Z,5E)-3-phenyl-2-(phenylimino)-5-(2,2,2-trifluoro-1-((3-trifluoromethylphenyl)amino)ethylidene)thiazolidine-4-thione

[0118]

[0119] Add 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(3-trifluoromethylphenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether into a 15 mL reaction tube. Place it in an oil bath at 50 °C under an air atmosphere and react for 48 h; cool to room temperature. Dilute the reaction solution with ethyl acetate, wash it three times with water, and dry the organic phase with anhydrous Na 2 SO 4 Dry, filter, concentrate, and purify by column chromatography to obtain 29.6 mg of the target product with a yield of 56%.

[0120] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0121] 1 H NMR(500MHz,Chloroform-d)δ13.55(s,1H),7.59(t,J=7.8Hz,2H),7.52(d,J=7.5Hz,2H),7.50–7.46(m,1H),7.41(s,1H),7.38–7.31(m,5H),7.13(dd,J=8.2,6.7Hz,1H),6.99–6.94(m,2H).

[0122] 13 C NMR(126MHz,Chloroform-d)δ188.5,154.8,148.9,139.1,138.8(q,J=33.1Hz),137.1,131.9(q,J=32.8Hz),129.9,129.8,129.5,129.4,128.7,127.7,124.9,123.5(q,J=272.6Hz),123.3(q,J=3.9Hz),121.3,120.8(q,J=281.2Hz),120.7,106.9.

[0123] 19 F NMR(471MHz,Chloroform-d)δ-59.31,-62.81.

[0124] HRMS(ESI-TOF) m / z: calcd for C 24 H 15 F 6 N 3 S 2 + : 524.0685 (M + H) + , found: 524.0686. -2-(Phenylimino)

[0125] Example 12

[0126] (2Z,5E)-5-(2,2-Difluoro-1-(phenylamino)ethylidene)-3-phenyl-2-(phenylimino)thiazolidine-4-thione

[0127]

[0128] 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1-difluoro-N-phenylpropan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 16.6 mg of the target product with a yield of 38%.

[0129] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0130] 1 H NMR (500 MHz, Chloroform-d) δ 13.93 (s, 1H), 7.58 (t, J = 7.7 Hz, 2H), 7.51–7.47 (m, 1H), 7.43–7.36 (m, 4H), 7.31 (q, J = 7.6 Hz, 3H), 7.18 (d, J = 7.8 Hz, 2H), 7.09 (t, J = 7.4 Hz, 1H), 6.97 (d, J = 7.1 Hz, 2H), 6.43 (t, J = 52.1 Hz, 1H).

[0131] 1313C NMR (126 MHz, Chloroform-d) δ 186.5, 156.1, 149.5, 143.7 (q, J = 25.0 Hz), 137.4, 136.2, 129.8, 129.6, 129.3, 129.2, 129.0, 127.3, 125.0, 124.4, 120.9, 110.1 (t, J = 244.6 Hz), 102.0.

[0132] 19 19F NMR (471 MHz, Chloroform-d) δ -117.02.

[0133] HRMS (ESI-TOF) m / z: calcd for C 23 H 17 F 2 N 3 S 2 + : 438.0905 (M+H) + , found: 438.0905.

[0134] Example 13

[0135] (2Z,5E)-5-(2,2,3,3,3-Pentafluoro-1-(phenylamino)propylidene)-3-phenyl-2-(phenylimino)thiazolidine-4-thione

[0136]

[0137] 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-3,3,4,4,4-pentafluoro-N-phenylbutan-2-imine, 0.3 mmol of sodium trifluoromethanesulfonate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 2SO 4 , filtered, concentrated, and purified by column chromatography to obtain 20 mg of the target product with a yield of 40%.

[0138] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0139] 1¹H NMR (500 MHz, Chloroform-d) δ 13.84 (s, 1H), 7.58 (t, J = 7.8 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.39–7.33 (m, 4H), 7.32 (d, J = 8.2 Hz, 2H), 7.29 (t, J = 7.4 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.11 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 7.4 Hz, 2H).

[0140] 13 ¹³C NMR (126 MHz, Chloroform-d) δ 187.7, 155.1, 149.0, 139.4 (q, J = 23.4 Hz), 137.9, 137.4, 129.7, 129.4, 129.3, 128.9, 128.7, 127.3, 126.8, 124.6, 120.8, 106.7.

[0141] 19 ¹⁹F NMR (471 MHz, Chloroform-d) δ -81.72, -100.54– -119.00 (m).

[0142] HRMS (ESI-TOF) m / z: calcd for C 24 H 16 F 5 N 3 S 2 + : 506.0779 (M+H) + , found: 506.0779.

[0143] Example 14

[0144] (2Z,5E)-5-(2,2,3,3,4,4,4-Heptafluoro-1-(phenylamino)butylidene)-3-phenyl-2-(phenylimino)thiazolidine-4-thione

[0145]

[0146] 0.3 mmol of phenyl isothiocyanate, 0.1 mmol of (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-3,3,4,4,5,5,5-heptafluoro-N-phenylpentan-2-imine, 0.3 mmol of sodium trifluoromethanesulfonate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried over anhydrous Na2 SO 4 It was dried, filtered, concentrated, and purified by column chromatography to obtain 22.1 mg of the target product with a yield of 40%.

[0147] The nuclear magnetic resonance and high-resolution mass spectrometry characterization of the target product are as follows:

[0148] 1 H NMR(500MHz,Chloroform-d)δ13.78(s,1H),7.60–7.55(m,2H),7.51–7.47(m,1H),7.39–7.34(m,3H),7.34–7.31(m,3H),7.28(t,J=7.3Hz,1H),7.16(d,J=7.7Hz,2H),7.13–7.08(m,1H),6.98–6.93(m,2H).

[0149] 13 C NMR(126MHz,Chloroform-d)δ187.8,155.0,148.9,139.1(d,J=23.3Hz),138.0,137.4,129.7,129.4,129.3,128.9,128.7,127.2,126.6,124.6,120.8,107.5.

[0150] 19 F NMR(471MHz,Chloroform-d)δ-80.17(t,J=10.6Hz),-106.12(q,J=10.6Hz),-123.46–-123.57(m).

[0151] HRMS(ESI-TOF)m / z:calcd for C 25 H 16 F 7 N 3 S 2 + :556.0747(M+H) + ,found:556.0748.

[0152] Example 15

[0153] (2Z,5E)-5-(1-((4-Bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(4-methoxyphenyl)-2-((4-methoxyphenyl)imino)thiazolidine-4-thione Preparation

[0154]

[0155] 0.3 mmol of 4-methoxyphenyl isothiocyanate, ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine 0.1 mmol, sodium trifluoromethanesulfinate 0.3 mmol and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 , filtered, concentrated, and purified by column chromatography to obtain 45.5 mg of the target product with a yield of 77%.

[0156] The NMR and high-resolution mass spectrometry of the target product are characterized as follows:

[0157] 1 H NMR (500 MHz, Chloroform-d) δ 13.55 (s, 1H), 7.50–7.43 (m, 2H), 7.28–7.23 (m, 2H), 7.09–7.04 (m, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.94–6.90 (m, 2H), 6.89–6.85 (m, 2H), 3.83 (s, 3H), 3.78 (s, 3H).

[0158] 13 C NMR (126 MHz, Chloroform-d) δ 188.3, 159.9, 156.8, 154.9 (q, J = 3.2 Hz), 142.2, 138.9 (q, J = 32.7 Hz), 137.4, 132.3, 129.7, 129.6, 126.1, 121.8, 120.7 (q, J = 247.4 Hz), 120.1, 115.0, 114.5, 105.9, 55.3.

[0159] 19 F NMR (471 MHz, Chloroform-d) δ -59.21.

[0160] HRMS (ESI-TOF) m / z: calcd for C 25 H 19 F 3 N 3 O 2 S 2 Br + : 594.0127 (M+H) + , found: 594.0127.

[0161] Example 16

[0162] Preparation of (2Z,5E)-5-(1-((4-bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(4-methylphenyl)-2-((4-methylphenyl)imino)thiazolidine-4-thione

[0163]

[0164] 0.3 mmol of 4-methylphenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 40.1 mg of the target product with a yield of 71%.

[0165] The NMR and high-resolution mass spectrometry characterization of the target product are as follows:

[0166] 1 H NMR(500MHz,Chloroform-d)δ13.54(s,1H),7.49–7.45(m,2H),7.37(d,J=8.1Hz,2H),7.26–7.21(m,2H),7.13(d,J=8.0Hz,2H),7.01(d,J=8.4Hz,2H),6.87–6.83(m,2H),2.42(s,3H),2.32(s,3H).

[0167] 13 C NMR(126MHz,Chloroform-d)δ188.2,154.9(q,J=3.2Hz),146.5,139.5,138.9(q,J=32.8Hz),137.4,134.5,134.3,132.3,130.5,129.9,128.4,126.1,120.8(q,J=281.1Hz),120.5,120.1,106.0,21.4,21.0.

[0168] 19 F NMR(471MHz,Chloroform-d)δ-59.22.

[0169] HRMS(ESI-TOF)m / z:calcd for C25 H 19 F 3 N 3 S 2 Br + :562.0229(M+H) + ,found:562.0230.

[0170] Example 17

[0171] (2Z,5E)-5-(1-((4-Bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(4-tert-butylphenyl)-2-((4-tert-butylphenyl)imino)thiazolidine-4-thione Preparation

[0172]

[0173] Add 0.3 mmol of 4-tert-butylphenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether to a 15 mL reaction tube, place it in an oil bath at 50 °C under an air atmosphere, and react for 48 h; cool to room temperature, dilute the reaction solution with ethyl acetate, wash it three times with water, and dry the organic phase with anhydrous Na 2 SO 4 Dry, filter, concentrate, and purify by column chromatography to obtain 56.8 mg of the target product with a yield of 88%.

[0174] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0175] 1 H NMR(500MHz,Chloroform-d)δ13.57(s,1H),7.58–7.54(m,2H),7.49–7.45(m,2H),7.36–7.32(m,2H),7.28–7.23(m,2H),7.02(d,J=8.5Hz,2H),6.90(d,J=8.5Hz,2H),1.36(s,9H),1.30(s,9H).

[0176] 1313C NMR (126 MHz, Chloroform-d) δ 188.2, 154.3, 152.1, 147.7, 146.1, 138.9 (q, J = 33.0 Hz), 137.5, 134.5, 132.3, 128.0, 126.6, 126.2, 126.1, 120.9 (q, J = 281.2 Hz), 120.2, 120.1, 106.1, 34.8, 34.4, 31.4, 31.3.

[0177] 19 19F NMR (471 MHz, Chloroform-d) δ -59.21.

[0178] HRMS (ESI-TOF) m / z: calcd for C 31 H 31 F 3 N 3 S 2 Br + : 646.1168 (M+H) + , found: 646.1168.

[0179] Example 18

[0180] (2Z,5E)-5-(1-((4-Bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(4-fluorophenyl)-2-((4-fluorophenyl)imino)thiazolidine-4-thione Preparation

[0181]

[0182] 0.3 mmol of 4-fluorophenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, placed in an oil bath at 50 °C under an air atmosphere, and reacted for 48 h; cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 filtered, concentrated, and purified by column chromatography to obtain 37 mg of the target product with a yield of 65%.

[0183] The NMR and high-resolution mass spectrometry characterizations of the target product are as follows:

[0184] 11H NMR (500 MHz, Chloroform-d) δ 13.65 (s, 1H), 7.51–7.44 (m, 2H), 7.34–7.29 (m, 2H), 7.28–7.21 (m, 2H), 7.03 (tq, J=5.8, 3.2 Hz, 4H), 6.95–6.88 (m, 2H).

[0185] 13 13C NMR (126 MHz, Chloroform-d) δ 187.8, 162.7 (d, J=249.9 Hz), 160.0 (d, J=243.8 Hz), 155.4, 144.8 (q, J=2.5 Hz), 139.7 (q, J=32.8 Hz), 137.0, 132.7, 132.4, 130.7 (d, J=8.9 Hz), 126.2, 122.1 (d, J=8.1 Hz), 120.7 (q, J=281.5 Hz), 120.5, 116.9 (d, J=23.1 Hz), 116.2 (d, J=22.6 Hz), 105.0.

[0186] 19 19F NMR (471 MHz, Chloroform-d) δ -59.06, -110.68, -117.96.

[0187] HRMS (ESI-TOF) m / z: calcd for C 23 H 13 F 5 N 3 S 2 Br + : 569.9728 (M+H) + , found: 569.9728.

[0188] Example 19

[0189] Preparation of (2Z,5E)-5-(1-((4-bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(2-fluorophenyl)-2-((2-fluorophenyl)imino)thiazolidine-4-thione

[0190]

[0191] 0.3 mmol of 2-fluorophenyl isothiocyanate, ((E)-3-(dimethyl(oxo)-λ 60.1 mmol of (sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfonate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; after cooling to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 27.7 mg of the target product with a yield of 49%.

[0192] The NMR and high-resolution mass spectrometry characterization of the target product are as follows:

[0193] 1 H NMR (500 MHz, Chloroform-d) δ 13.68 (s, 1H), 7.53–7.46 (m, 3H), 7.42 (td, J = 7.6, 7.1, 1.8 Hz, 1H), 7.37–7.33 (m, 1H), 7.33–7.27 (m, 1H), 7.13–7.07 (m, 3H), 7.05 (d, J = 8.4 Hz, 2H), 6.99 (dtd, J = 8.4, 4.4, 1.6 Hz, 1H).

[0194] 13 C NMR (126 MHz, Chloroform-d) δ 187.2, 157.8 (d, J = 253.1 Hz), 156.0, 153.4 (d, J = 247.1 Hz), 140.0 (q, J = 32.9 Hz), 136.8, 136.5 (d, J = 12.5 Hz), 132.4, 131.7 (d, J = 7.8 Hz), 130.7, 126.5, 125.9 (d, J = 7.2 Hz), 125.1 (d, J = 3.9 Hz), 124.6 (q, J = 3.8 Hz), 124.4 (d, J = 13.0 Hz), 122.6, 120.7, 120.6 (q, J = 281.2 Hz), 117.1 (d, J = 19.2 Hz), 116.5 (d, J = 19.6 Hz), 104.8.

[0195] 19 F NMR (471 MHz, Chloroform-d) δ -59.01, -119.11, -124.92.

[0196] HRMS (ESI-TOF) m / z: calcd for C 23 H 13 F 5 N 3 S2 Br + : 569.9728 (M+H) + , found: 569.9728.

[0197] Example 20

[0198] Preparation of (2Z,5E)-5-(1-((4-bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(2-methoxyphenyl)-2-((2-methoxyphenyl)imino)thiazolidine-4-thione

[0199]

[0200] 0.3 mmol of 2-methoxyphenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, and the mixture was placed in an oil bath at 50 °C under an air atmosphere and reacted for 48 h; cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 29.7 mg of the target product with a yield of 50%.

[0201] The NMR and high-resolution mass spectrometry characterization of the target product are as follows:

[0202] 1 H NMR (500 MHz, Chloroform-d) δ 13.52 (s, 1H), 7.50–7.43 (m, 3H), 7.33 (dd, J = 7.7, 1.8 Hz, 1H), 7.16–7.06 (m, 3H), 7.02 (d, J = 8.2 Hz, 2H), 6.95–6.86 (m, 3H), 3.89 (s, 3H), 3.77 (s, 3H).

[0203] 13 C NMR (126 MHz, Chloroform-d) δ 188.1, 155.2, 155.0, 150.4, 138.6 (q, J = 32.9 Hz), 138.6, 137.5, 132.2, 131.1, 130.0, 126.1, 125.7, 125.5, 121.4, 121.4, 121.1, 120.9 (q, J = 281.3 Hz), 120.0, 112.9, 112.4, 106.4, 56.0, 55.8.

[0204] 19 F NMR (471 MHz, Chloroform-d) δ -59.25.

[0205] HRMS (ESI-TOF) m / z: calcd for C 25 H 19 F 3 N 3 O 2 S 2 Br + : 594.0127 (M+H) + , found: 594.0127.

[0206] Example 21

[0207] (2Z,5E)-5-(1-((4-Bromophenyl)amino)-2,2,2-trifluoroethyl)-3-(3-methoxyphenyl)-2-((3-methoxyphenyl)imino)thiazolidine-4-thione Preparation

[0208]

[0209] 0.3 mmol of 3-methoxyphenyl isothiocyanate, 0.1 mmol of ((E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, 0.3 mmol of sodium trifluoromethanesulfinate and 1.5 mL of methyl tert-butyl ether were added to a 15 mL reaction tube, placed in an oil bath at 50 °C under an air atmosphere, and reacted for 48 h; cooled to room temperature, the reaction solution was diluted with ethyl acetate, washed three times with water, and the organic phase was dried with anhydrous Na 2 SO 4 dried, filtered, concentrated, and purified by column chromatography to obtain 38 mg of the target product with a yield of 64%.

[0210] The NMR and high-resolution mass spectrometry characterization of the target product are as follows:

[0211] 1 H NMR (500 MHz, Chloroform-d) δ 13.60 (s, 1H), 7.49 (t, J = 8.3 Hz, 3H), 7.25–7.22 (m, 1H), 7.03 (dd, J = 9.7, 3.8 Hz, 3H), 6.96–6.92 (m, 1H), 6.88 (t, J = 2.2 Hz, 1H), 6.68 (dd, J = 8.1, 2.3 Hz, 1H), 6.57 (dd, J = 7.6, 1.4 Hz, 1H), 6.50 (t, J = 2.2 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H).

[0212] 13 C NMR (126 MHz, Chloroform-d) δ 188.0, 160.6, 160.5, 155.0 (q, J=2.0 Hz), 139.3 (q, J=32.7 Hz), 138.1, 137.3, 132.3, 130.4, 130.2, 126.2, 120.8 (q, J=281.1 Hz), 120.8, 115.1, 114.6, 112.7, 110.7, 106.4, 105.7, 55.4, 55.3.

[0213] 19 F NMR (471 MHz, Chloroform-d) δ -59.17.

[0214] HRMS (ESI-TOF) m / z: calcd for C 25 H 19 F 3 N 3 O 2 S 2 Br + : 594.0127 (M+H) + , found: 594.0127.

[0215] As described above, it is only the preferred embodiment of the present invention, so the scope of implementation of the present invention cannot be limited thereby. That is, equivalent changes and modifications made according to the scope of the present invention patent and the content of the specification should still fall within the scope covered by the present invention.

Claims

1. A method for preparing a thiazolidine-4-thione derivative, characterized in that: It includes the following steps: (1) Mix an isothiocyanate or its derivative, a sulfonium ylide, an additive, and an organic solvent, and react at 20-90 °C for 12-48 h under an air atmosphere; (2) Dilute the material obtained in step (1) with ethyl acetate and wash it with water, then separate to obtain the organic phase; (3) The above organic phase is successively dried, filtered, concentrated, and subjected to column chromatography or thin-layer chromatography to obtain a thiazolidine-4-thione derivative, and its structural formula is The structural formula of the above isothiocyanate or its derivative is wherein, R 3 is hydrogen, alkyl, alkoxy, halogen, trifluoromethyl or benzyloxy; The structural formula of the above-mentioned sulfonium ylide is wherein R 1 is hydrogen, alkyl, alkoxy, trifluoromethyl, halogen, nitro or cyano, and R 2 is hydrogen, halogen, trifluoromethyl or pentafluoroethyl; The above additives are selected from sodium trifluoromethanesulfonate, potassium trifluoromethanesulfonate, sodium p-toluenesulfonate, sodium methylsulfonate, sodium sulfate, sodium bisulfite, sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium thiosulfate pentahydrate, sodium dithionite, sodium persulfate, sodium amidosulfate, sodium formate, sodium difluorochloroacetate, sodium chloride, sodium bromide, sodium iodide, sodium periodate, sodium trifluoromethylsulfinate, sodium lignosulfonate, sodium benzenesulfinate, sodium nitrite, and sodium pivalate.

2. The preparation method according to claim 1, characterized in that: The halogen is fluorine, chlorine or bromine.

3. The preparation method according to claim 2, characterized in that: The sulfonium ylide is selected from (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-methylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-fluorophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-chlorophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-bromophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-trifluoromethylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(4-nitrophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(2-bromophenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(3-methoxyphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1,1-trifluoro-N-(3-trifluoromethylphenyl)propan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-1,1-difluoro-N-phenylpropan-2-imine, (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-3,3,4,4,4-pentafluoro-N-phenylbutan-2-imine and (E)-3-(dimethyl(oxo)-λ 6 -sulfinyl)-3,3,4,4,5,5,5-heptafluoro-N-phenylpentan-2-imine.

4. The preparation method according to claim 1, characterized in that: The additive is sodium trifluoromethylsulfinate.

5. The preparation method according to claim 1, characterized in that: The organic solvent is ethanol, tert-butanol, ether, ethylene glycol dimethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, 1,2-dichloroethane, toluene, 1,4-dioxane, tetrahydrofuran, hexafluoroisopropanol, methyl tert-butyl ether or acetonitrile.

6. The preparation method according to claim 5, characterized in that: The organic solvent is methyl tert-butyl ether.

7. The preparation method according to claim 1, characterized in that: The isothiocyanate or its derivative is phenyl isothiocyanate, 4-methoxyphenyl isothiocyanate, 4-methylphenyl isothiocyanate, 4-tert-butylphenyl isothiocyanate, 4-fluorophenyl isothiocyanate, 2-fluorophenyl isothiocyanate, 2-methoxyphenyl isothiocyanate or 3-methoxyphenyl isothiocyanate.

8. The preparation method according to claim 1, characterized in that: The organic solvent is methyl tert-butyl ether, and the additive is sodium trifluoromethylsulfinate.

9. The preparation method according to any one of claims 1 to 8, characterized in that: The molar ratio of the isothiocyanate or its derivative, the sulfonium ylide, and the additive is 1-4:1:0-4, and for every 0.01 mmol of the sulfonium ylide, the organic solvent is 0.1-2 mL.

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