CN108658934B - Preparation method of 1, 2-disulfide-3-thioketone derivative synthesized by copper catalysis - Google Patents
Preparation method of 1, 2-disulfide-3-thioketone derivative synthesized by copper catalysis Download PDFInfo
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- CN108658934B CN108658934B CN201810585488.7A CN201810585488A CN108658934B CN 108658934 B CN108658934 B CN 108658934B CN 201810585488 A CN201810585488 A CN 201810585488A CN 108658934 B CN108658934 B CN 108658934B
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Abstract
The invention discloses a 1, 2-dithio-3-thioketone derivative synthesized by copper-catalyzed trifluoropropyne defluorination and cyclization, which takes a 2-chloro-3, 3, 3-trifluoro-1 propylene compound as a substrate, cuprous bromide is added into the substrate as a catalyst, cesium carbonate is taken as alkali, tetramethylethylenediamine is taken as a ligand, elemental sulfur is taken as a sulfur source and is stirred and reacted in a solvent N, N-dimethylformamide for 12 hours at the temperature of 120 ℃; after the reaction is finished, filtering the reaction solution, extracting the filtrate twice by using a saturated sodium chloride solution, performing back extraction once, drying the separated organic phase by using anhydrous sodium sulfate, filtering again, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, performing column layer separation on the residue by using a silica gel column, leaching by using an eluent, collecting an effluent liquid containing a target product, combining the effluent liquid, and removing the solvent by vacuum concentration to obtain the target product. The invention has the advantages of simple and easily obtained raw materials, novel and simple preparation process, less pollution, low energy consumption and high yield.
Description
Technical Field
The invention relates to the field of organic chemistry, in particular to a preparation method of a 1, 2-dithio-3-thioketone derivative synthesized by copper catalysis.
Background
1, 2-dithio-3-thione is an important structural unit of various medicaments, and has remarkable biological and medical properties including chemotherapy, oxidation resistance and radiation protection. For example, oteraz has anti-HIV activity (see biochem. biophysis. res. comm.1996,221,548), NOSH-1 was shown to have excellent anti-inflammatory effects (acsmed. chem. lett.2012,3,257), S-tanshinol has some therapeutic effect on male infertility (CN 102417501a), anethol trithione ADT was used as a choleretic (rev. susse Praxis med.1979,68,1063).
In the prior art, 1, 2-dithio-3The thioketone being formed by reacting a terminal alkyne with CS2And S8Obtained by multi-step reaction at-78 ℃ (Tetrahedron Lett.2014,55,5283). Or by reacting beta-ketoesters or ketones with specific thionating agents, e.g. P2S5、CS2Or Lawesson reagent via a multi-step reaction (Tetrahedron lett.1993,34,3703 and j.org.chem.2002,67,6461). In 2016, Singh and his colleagues reported a process for the efficient synthesis of 1, 2-dithio-3-thione derivatives from alpha-allyl dithioester catalyzed by indium trichloride with elemental sulphur (J.org.chem.2016,81,11594). However, since these reaction conditions are severe, some of them require a reaction at-78 ℃, and the reaction conditions are difficult; some raw materials are difficult to prepare, and the economic cost is too high; the practicality and applicability of these methods are limited for various reasons and cannot be really popularized on a large scale.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a preparation method of a 1, 2-dithio-3-thioketone derivative synthesized by copper catalysis; the raw materials are easy to prepare, the economic cost is low, the reaction conditions are easy, the 1, 2-dithio-3-thioketone derivative can be directly synthesized, an intermediate product does not need to be separated, and the economy is high.
In order to achieve the purpose, the invention provides the following technical scheme: a1, 2-dithio-3-thioketone derivative synthesized by copper-catalyzed trifluoro-propyne defluorination and cyclization, wherein the molecular formula of the 1, 2-dithio-3-thioketone derivative is as follows:
the catalyst is prepared by reacting 2-chloro-3, 3, 3-trifluoro-1 propylene compound and sulfur simple substance in a reaction system containing ligand and alkali under the action of a catalyst; the molecular formula of the compound of the 2-chloro-3, 3, 3-trifluoro-1 propylene is as follows:
The catalyst is any one of cuprous bromide, cuprous acetate, cuprous chloride and cuprous iodide.
The reaction temperature is 80-120 ℃, and the reaction time is 12 h.
The ligand is any one of tetramethyl ethylenediamine, 1,10 phenanthroline and bipyridine.
The alkali is any one of cesium carbonate and potassium phosphate.
The whole reaction is carried out in a solvent, wherein the solvent is any one of N, N-dimethylformamide, acetonitrile and dimethyl sulfoxide.
During the reaction, the molar parts of the substances added are as follows:
1 part of a compound containing 2-chloro-3, 3, 3-trifluoro-1-propene;
0.1-0.2 part of catalyst;
2 parts of alkali;
0.2-0.4 part of ligand;
1-1.5 parts of elemental sulfur.
After the reaction of the 2-chloro-3, 3, 3-trifluoro-1 propylene compound and the elemental sulfur is finished, a filtering and purifying process is carried out, wherein the filtering and purifying process comprises the following steps: filtering, extracting, drying the organic phase, filtering, evaporating, carrying out silica gel column chromatography, and finally carrying out vacuum concentration on the eluted effluent to obtain the product.
The extract is a saturated sodium chloride solution.
When the silica gel column chromatography is carried out, the eluent is a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of the mixed solution is 30: 1.
The invention has the beneficial effects that: the target product can be directly synthesized, the intermediate product does not need to be separated, the target product can be obtained only by stirring and reacting under normal pressure, the yield can reach 88 percent to the maximum, the process engineering is greatly simplified, the energy consumption is reduced, and the method has the advantage of high yield; in addition, the waste solution is less in the reaction process, and other polluted gases and liquid are not discharged, so that the method reduces the discharge of the waste solution, and has the advantages of protecting the environment and ensuring the health of operators; in addition, a series of 5-phenyl substituted 1, 2-dithio-3-thioketone derivatives can be prepared, and the method has strong substrate universality. Thus, the invention fills the blank of the method for preparing the 5-substituted 1, 2-dithiol-3-thioketone derivative at the present stage, promotes the development of the polysubstituted 1, 2-dithiol-3-thioketone derivative, provides powerful guarantee for developing the medicament containing the 1, 2-dithiol-3-thioketone derivative and provides reference for the conversion of fluoride into sulfide.
Drawings
FIG. 1 is a diagram showing the reaction mechanism of the present invention.
Detailed Description
The first embodiment is as follows: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 37.0 mg of red solid 5-phenyl-3H-1, 2-disulfide-3-thioketone with the yield of 88%. m.p.122-124 ℃.1H NMR(500MHz,CDCl3)δ7.57(d,J＝7.0Hz,2H),7.47(d,J＝7.0Hz,2H),7.42-7.39(m,1H),7.35(s,1H).13C NMR(125MHz,CDCl3)δ215.5,172.8,135.9,132.1,131.6,129.5,126.8.LRMS(EI 70ev)m/z(％):210(M+,79),146(20),145(100),122(29).
The second embodiment is as follows: 44.1 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2-methylbenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mmolG (0.3mmol) S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, eluting with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 33.6 mg of red oily liquid 5- (o-tolyl) -3H-1, 2-disulfide-3-thioketone with the yield of 75%.1H NMR(500MHz,CDCl3)δ7.36-7.32(m,2H),7.26-7.22(m,2H),7.06(s,1H),2.36(s,3H).13C NMR(125MHz,CDCl3)δ215.8,172.9,139.3,136.0,131.4,131.0,130.6,129.2,126.4,20.4.LRMS(EI70ev)m/z(％):224(M+,100),191(27),159(48),147(17).
The third concrete embodiment: 44.1 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -3-methylbenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 36.8 mg of red oily liquid 5- (m-tolyl) -3H-1, 2-disulfide-3-thione with the yield of 82%.1H NMR(500MHz,CDCl3)δ7.38-7.36(m,3H),7.30-7.29(m,2H),2.35(s,3H).13C NMR(125MHz,CDCl3)δ215.5,173.1,139.6,135.8,132.9,131.6,129.4,127.4,124.0,21.3.LRMS(EI 70ev)m/z(％):224(M+,86),207(15),159(100),115(42).
The fourth concrete embodiment: 44.1 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -4-methylbenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, leaching with a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 30:1, collecting effluent according to an actual gradient, detecting by TLC, combining the effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 27.8 mg of red solid 5- (p-tolyl) -3H-1, 2-disulfide-3-thioketone with a yield of 62%. m.p.117-119 ℃.1H NMR(500MHz,CDCl3)δ7.47(d,J＝8.0Hz,2H),7.35(s,1H),7.21(d,J＝8.0Hz,2H),2.34(s,3H).13C NMR(125MHz,CDCl3)δ215.4,173.1,143.1,135.4,130.3,128.9,126.8,21.5.LRMS(EI70ev)m/z(％):224(M+,86),207(80),159(100),116(23).
The fifth concrete embodiment: 46.9 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -2, 4-dimethylbenzene, 5.6 mg of cuprous bromide (20 mmol%) and 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate, removing solvent to obtain residue, subjecting the residue to silica gel column chromatography, eluting with mixed solution of petroleum ether and ethyl acetate at volume ratio of 30:1, collecting eluate according to actual gradient, detecting by TLC, mixing the eluates, and collecting eluate containing productThe effluent was evaporated in a rotary evaporator to remove the solvent and dried in vacuo to give 38.1 mg of 5- (2, 4-dimethylphenyl) -3H-1, 2-dithio-3-thione as a red solid in 80% yield. m.p.79-81 ℃.1HNMR(500MHz,CDCl3)δ7.26(d,J＝8.0Hz,1H),7.07-7.06(m,2H),7.03(d,J＝8.0Hz,1H),2.33(s,3H),2.30(s,3H).13C NMR(125MHz,CDCl3)δ215.8,173.4,141.5,139.1,135.8,132.2,129.2,127.8,127.2,21.2,20.4.LRMS(EI 70ev)m/z(％):238(M+,94),224(72),205(25),173(47).
The sixth specific embodiment: 46.9 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -4-ethylbenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 37.1 mg of red solid 5- (4-ethylphenyl) -3H-1, 2-dithio-3-thioketone with the yield of 78%. m.p.115-116 ℃.1H NMR(500MHz,CDCl3)δ7.51(d,J＝8.0Hz,2H),7.36(s,1H),7.24(d,J＝8.0Hz,2H),2.66-2.62(m,2H),1.21-1.18(m,3H).13C NMR(125MHz,CDCl3)δ215.4,173.2,149.3,135.4,129.1,127.0,126.9,28.8,15.1.LRMS(EI 70ev)m/z(％):238(M+,89),209(25),173(100),115(36).HRMS(ESI)Calcd for C11H11S3 +([M+H]+)239.0017,found 239.0019.
The seventh specific embodiment: 47.3 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -3-methoxybenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of carbonic acidCesium was added to 2mL of solvent N, N-dimethylformamide. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 30.2 mg of red solid 5- (3-methoxyphenyl) -3H-1, 2-dithio-3-thioketone with a yield of 63%. m.p.113-115 ℃.1HNMR(500MHz,CDCl3)δ7.35-7.30(m,2H),7.16(d,J＝7.5Hz,1H),7.06(s,1H),7.01(d,J＝8.5Hz,1H),3.79(s,3H).13C NMR(125MHz,CDCl3)δ215.5,172.7,160.3,136.0,132.8,130.7,119.3,117.7,112.3,55.5.LRMS(EI 70ev)m/z(％):240(M+,100),209(20),207(100),175(82).
The eighth embodiment: 47.3 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -4-methoxybenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 26.4 mg of red solid 5- (4-methoxyphenyl) -3H-1, 2-dithio-3-thioketone with the yield of 55%. m.p.110-111 ℃.1HNMR(500MHz,CDCl3)δ7.54(d,J＝8.5Hz,2H),7.31(s,1H),6.90(d,J＝8.5Hz,2H),3.81(s,3H).13C NMR(125MHz,CDCl3)δ215.1,172.9,162.9,134.6,128.5,124.2,115.0,55.6.LRMS(EI 70ev)m/z(％):240(M+,75),208(20),207(100),175(69).
The specific embodiment is nine: 50.5 mg (0.2mmol) of (4- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) phenyl) (methyl) sulfane, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.03mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling the solvent by using a rotary evaporator, and performing vacuum drying to obtain 26.6 mg of red solid 5- (4- (methylthio) phenyl) -3H-1, 2-dithio-3-thioketone with the yield of 52%. m.p.86-89 ℃ C.1H NMR (500MHz, CDCl)3)δ7.57(d,J＝8.0Hz,2H),7.43(s,1H),7.29(d,J＝8.0Hz,2H),2.54(s,3H).13C NMR(125MHz,CDCl3)δ215.3,172.4,145.2,135.2,127.8,127.0,126.2,14.9.LRMS(EI 70ev)m/z(％):256(M+,89),224(73),241(35),209(24).HRMS(ESI)Calcdfor C10H9S4 +([M+H]+)256.9582,found 256.9575.
The specific embodiment ten: 52.5 mg (0.2mmol) of 1- (tert-butyl) -4- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, separating to obtain organic phase, drying with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate, removing solvent to obtain residue, performing silica gel column chromatography on the residue, and performing volume extraction with petroleum ether and ethyl acetateAnd eluting the mixed solution with the ratio of 30:1, collecting effluent according to actual gradient, detecting by TLC, combining the effluent containing the product, distilling by a rotary evaporator to remove the solvent, and drying in vacuum to obtain 30.3 mg of red oily liquid 5- (4- (tert-butyl) phenyl) -3H-1, 2-disulfide-3-thioketone with the yield of 57%.1H NMR(500MHz,CDCl3)δ7.52(d,J＝8.0Hz,2H),7.42(d,J＝8.0Hz 2H),7.37(s,1H),1.28(s,9H).13C NMR(125MHz,CDCl3)δ215.5,173.1,156.1,135.4,128.9,126.7,126.6,35.1,31.0.LRMS(EI 70ev)m/z(％):266(M+,100),251(57),201(36),171(19).
The first specific embodiment: 56.5 mg (0.2mmol) of 4- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -1,1' -biphenyl, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate to remove the solvent to obtain the residue, performing silica gel column chromatography on the residue, eluting with a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 30:1, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and drying in vacuum to obtain the red solid 5- ([1,1' -biphenyl)]24.0 mg of (E) -4-yl) -3H-1, 2-dithio-3-thione (E), yield 42%. m.p.119-122 ℃.1H NMR(500MHz,CDCl3)δ7.68-7.63(m,4H),7.55(d,J＝7.5Hz,2H),7.43-7.40(m,3H),7.34(d,J＝7.0Hz,1H).13C NMR(125MHz,CDCl3)δ215.5,172.4,145.1,139.4,1357,130.5,129.1,128.5,128.2,127.4,127.1.LRMS(EI70ev)m/z(％):286(M+,100),254(21),209(37),153(45).
The specific example twelve: 59.7 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -4-phenoxybenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, 2mL of N, N-dimethylmethane as solvent were addedIn an amide. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 47.7 mg of red solid 5- (4-phenoxyphenyl) -3H-1, 2-dithio-3-thioketone with a yield of 79%. m.p.130-132 ℃.1HNMR(500MHz,CDCl3)δ7.53(d,J＝9.0Hz,2H),7.35-7.31(m,3H),7.16-7.13(m,1H),7.00(d,J＝8.0Hz,2H),6.96(d,J＝8.0Hz,2H).13C NMR(125MHz,CDCl3)δ215.2,172.3,161.4,155.3,135.1,130.1,128.6,125.9,124.8,120.1,118.4.LRMS(EI 70ev)m/z(％):302(M+,100),270(27),225(52),209(31).HRMS(ESI)Calcd for C15H11OS3 +([M+H]+)302.9967,found 32.9972.
The specific example thirteen: 44.9 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -3-fluorobenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice by using a saturated sodium chloride solution, performing back extraction once, drying an organic phase obtained by separation by using anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing elution by using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling by using a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 29.6 mg of a red solid 5- (3-fluorophenyl) -3H-1, 2-disulfide-3-thioketone with the yield of 65%. m.p.126-128 ℃.1H NMR(500MHz,CDCl3)δ7.43-7.37(m,2H),7.33(s,1H),7.28(d,J＝9.0Hz,1H),7.20-7.17(m,1H).13C NMR(125MHz,CDCl3)δ215.5,170.7,163.0(q,JC-F＝247.5Hz),136.5,133.6,131.4,122.7,119.0(d,JC-F＝21.3Hz),114.0(d,JC-F＝23.8Hz).LRMS(EI 70ev)m/z(％):228(M+,81),207(36),163(100),120(32).
The specific embodiment fourteen: 48.2 mg (0.2mmol) of 1-chloro-3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 31.3 mg of black solid 5- (3-chlorophenyl) -3H-1, 2-dithio-3-thioketone with the yield of 64%. m.p.106-108 ℃.1H NMR(500MHz,CDCl3)δ7.56(s,1H),7.47-7.44(m,2H),7.38-7.34(m,1H),7.32(s,1H).13C NMR(125MHz,CDCl3)δ215.4,170.5,136.4,135.7,133.2,131.9,130.8,126.9,125.0.LRMS(EI70ev)m/z(％):244(M+,100),209(53),212(62),137(27).
The specific embodiment fifteen: 57.1 mg (0.2mmol) of 1-bromo-3- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, separating to obtain organic phase, drying with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate, removing solvent to obtain residue, and collecting the residuePerforming silica gel column chromatography, eluting with a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 30:1, collecting eluate according to actual gradient, detecting by TLC, combining the eluate containing the product, distilling with a rotary evaporator to remove the solvent, and vacuum drying to obtain a black solid 5- (3-bromophenyl) -3H-1, 2-disulfide-3-thione 47.9 mg with a yield of 83%. m.p.123-125 ℃.1H NMR(500MHz,CDCl3)δ7.12(s,1H),7.60(d,J＝8.0Hz,1H),7.51(d,J＝7.5Hz,1H),7.31-7.28(m,2H).13C NMR(125MHz,CDCl3)δ215.4,170.4,136.4,134.8,133.5,131.0,129.7,125.4,123.6.LRMS(EI 70ev)m/z(％):289(M+,83),256(41),209(35),156(28).HRMS(ESI)Calcdfor C9H6BrS3 +([M+H]+)288.8810,found288.8812.
The specific embodiment is sixteen: 47.7 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -3-fluoro-2-methylbenzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 36.8 mg of red solid 5- (3-fluoro-2-methylphenyl) -3H-1, 2-disulfide-3-thioketone with the yield of 76%. m.p.115-117 ℃.1H NMR(500MHz,CDCl3)δ7.21-7.16(m,2H),7.13-7.10(m,1H),7.04(s,1H),2.27(s,3H).13C NMR(125MHz,CDCl3)δ215.7,170.9,161.5(d,JC-F＝245.0Hz),139.6,132.7,127.6,124.4,123.8(d,JC-F＝18.2Hz),117.6(d,JC-F＝22.5Hz),12.1.LRMS(EI 70ev)m/z(％):242(M+,100),209(24),177(54),133(84).HRMS(ESI)Calcd for C10H8FS3 +([M+H]+)242.9767,found 242.9756.
Specific example seventeen: 54.9 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) -4- (trifluoromethyl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg of S8(0.3mmol), 9.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 25.0 mg of red oily liquid 5- (4- (trifluoromethyl) phenyl) -3H-1, 2-disulfide-3-thione with the yield of 45%.1HNMR(500MHz,CDCl3)δ7.72(d,J＝8.5Hz,2H),7.69(d,J＝8.5Hz,2H),7.37(s,1H).13C NMR(125MHz,CDCl3)δ215.5,170.1,137.0,135.0,133.6(q,JC-F＝32.5Hz),127.3,126.6,123.4(q,JC-F＝271.0Hz).LRMS(EI 70ev)m/z(％):278(M+,68),213(100),170(16).
The specific embodiment eighteen: 51.3 mg (0.2mmol) of 1- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) naphthalene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate, removing solvent to obtain residue, subjecting the residue to silica gel column chromatography, eluting with mixed solution of petroleum ether and ethyl acetate at volume ratio of 30:1, collecting eluate according to actual gradient, detecting by TLC, mixing the eluates containing product, and rotary extractingThe solvent was distilled off by an evaporator, and dried in vacuo to give 38.5 mg of 5- (naphthalen-1-yl) -3H-1, 2-disulfide-3-thione as a red solid in 74% yield. m.p.140-142 ℃.1H NMR(500MHz,CDCl3)δ7.97-7.95(m,1H),7.89(d,J＝8.5Hz,1H),7.83-7.81(m,1H),7.56(d,J＝7.0Hz,1H),7.48-7.47(m,2H),7.44-7.40(m,1H),7.24(s,1H).13C NMR(125MHz,CDCl3)δ215.5,171.7,139.9,133.7,131.7,130.1,128.6,128.5,127.8,127.7,126.9,124.4.LRMS(EI 70ev)m/z(％):260(M+,100),228(37),196(12),152(21).
The specific examples are nineteen: 51.3 mg (0.2mmol) of 2- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) naphthalene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 37.4 mg of red solid 5- (naphthalene-2-yl) -3H-1, 2-disulfide-3-thioketone with the yield of 72%. m.p.68-71 ℃.1H NMR(500MHz,CDCl3)δ8.11(s,1H),7.86-7.80(m,3H),7.59(d,J＝8.5Hz,1H),7.55-7.51(m,2H),7.49(s,1H).13C NMR(125MHz,CDCl3)δ215.6,172.8,136.1,134.8,133.0,129.6,129.0,128.9,128.4,127.9,127.6,127.2,123.4.LRMS(EI 70ev)m/z(％):260(M+,100),228(43),196(32),151(21).
The specific embodiment twenty: 42.5 mg (0.2mmol) of 2- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) thiophene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting at 120 deg.C for 12 hr, and coolingFiltering the reaction solution to obtain a filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 24.2 mg of red solid 5- (thiophene-2-yl) -3H-1, 2-disulfide-3-thioketone with the yield of 56%. m.p.129 ℃.1H NMR(500MHz,CDCl3)δ7.52(d,J＝5.0Hz,1H),7.47(d,J＝3.5Hz,1H),7.26(s,1H),7.09-7.07(m,1H).13C NMR(125MHz,CDCl3)δ214.6,165.0,134.7,134.0,130.9,129.1,129.0.LRMS(EI70ev)m/z(％):216(M+,100),184(47),133(25),108(32).
The specific embodiment twenty one: 39.3 mg (0.2mmol) of 2- (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) furan, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg (40% mmol) of tetramethylethylenediamine, 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 20.8 mg of red solid 5- (furan-2-yl) -3H-1, 2-disulfide-3-thioketone with the yield of 52%. m.p.110-113 ℃.1H NMR(500MHz,CDCl3)δ7.57(d,J＝1.5Hz,1H),7.29(s,1H),6.91(d,J＝3.5Hz,1H),6.54-6.53(m,1H).13C NMR(125MHz,CDCl3)δ214.3,159.9,146.5,146.3,133.1,113.3,113.2.LRMS(EI70ev)m/z(％):200(M+,100),135(93),82(22),69(28).
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTIONTwenty-two: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 4.9 mg of cuprous acetate (20 mmol%), 76.9 mg (0.3mmol) of S8130.0 mg of cesium carbonate was added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 20.1 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with a yield of 49%.
The specific embodiment twenty three: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 4.0 mg of cuprous chloride (20 mmol%), 76.9 mg (0.3mmol) of S8130.0 mg of cesium carbonate was added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 17.6 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 42%.
The specific embodiment twenty four: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S8130.0 mg of cesium carbonate was added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, and separatingDrying the obtained organic phase by using anhydrous sodium sulfate, filtering again, carrying out rotary evaporation on the filtrate, removing the solvent to obtain a residue, carrying out silica gel column chromatography on the residue, carrying out elution by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1, collecting effluent liquid according to actual gradient, carrying out TLC detection, combining the effluent liquid containing the product, distilling by using a rotary evaporator to remove the solvent, and carrying out vacuum drying to obtain 24.5 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 59%.
The specific embodiment is twenty five: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 7.9 mg of cuprous iodide (20 mmol%), 76.9 mg (0.3mmol) of S8130.0 mg of cesium carbonate was added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 18.0 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 43%.
Specific example twenty-six: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S814.4 mg (40% mmol) of 1, 10-phenanthroline and 130.0 mg of cesium carbonate are added into 2mL of N, N-dimethylformamide serving as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate to remove the solvent to obtain the residue, subjecting the residue to silica gel column chromatography, eluting with mixed solution of petroleum ether and ethyl acetate at a volume ratio of 30:1, collecting the effluent according to actual gradient, detecting by TLC, mixing the effluent containing the product, and distilling with rotary evaporator to removeThe solvent was dried in vacuo to give 23.5 mg of 5-phenyl 3H-1, 2-disulfide-3-thione as a red solid in 56% yield.
The specific embodiment is twenty-seven: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S812.5 mg of bipyridine (40% mmol), 130.0 mg of cesium carbonate were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 26.0 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 62%.
The specific embodiment twenty eight: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 55.2 mg of potassium carbonate were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 26.0 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 62%.
Specific example twenty-nine: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S8，93 mg of tetramethylethylenediamine (40% mmol), 85.0 mg of potassium phosphate were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 15.1 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 36%.
Thirty of the specific embodiments: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate were added to 2mL of a dimethyl sulfoxide solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 27.3 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thione with the yield of 65%.
The specific embodiment is thirty-one: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate were added to 2mL of acetonitrile solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, back extracting once, separating the obtained organic phase, drying with anhydrous sodium sulfate,and (3) filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, leaching with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to an actual gradient, detecting by TLC, combining the effluent containing the product, distilling by a rotary evaporator to remove the solvent, and performing vacuum drying to obtain 9.7 mg of red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 23%.
The specific embodiment is thirty-two: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate were added to 2mL of a toluene solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice by using a saturated sodium chloride solution, performing back extraction once, drying an organic phase obtained by separation by using anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1, collecting effluent liquid according to actual gradient, performing TLC detection, combining the effluent liquid containing the product, distilling by using a rotary evaporator to remove the solvent, and performing vacuum drying to obtain a trace red solid 5-phenyl 3H-1, 2-dithio-3-thioketone with the yield of less than 10%.
The specific embodiment is thirty-three: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 100 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain a filtrate; extracting the filtrate twice with saturated sodium chloride solution, back-extracting once, drying the separated organic phase with anhydrous sodium sulfate, filtering again, rotary evaporating the filtrate to remove the solvent to obtain the residue, performing silica gel column chromatography on the residue, eluting with a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 30:1, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and vacuum drying to obtain the final productRed solid 5-phenyl 3H-1, 2-disulfide-3-thione in 63% yield of 26.5 mg.
The specific embodiment is thirty-four: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 76.9 mg (0.3mmol) of S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting at 80 ℃ for 12 hours, cooling after the reaction is finished, and filtering the reaction solution to obtain a filtrate; extracting the filtrate twice by using a saturated sodium chloride solution, performing back extraction once, drying an organic phase obtained by separation by using anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1, collecting effluent liquid according to actual gradient, performing TLC detection, combining the effluent liquid containing the product, distilling by using a rotary evaporator to remove the solvent, and performing vacuum drying to obtain a red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 21.0 mg of 50%.
The specific embodiment is thirty-five: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 1.2 eq 61.4 mg S89.3 mg of tetramethylethylenediamine (40% mmol), 130.0 mg of cesium carbonate, were added to 2mL of N, N-dimethylformamide as a solvent. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice by using a saturated sodium chloride solution, performing back extraction once, drying the separated organic phase by using anhydrous sodium sulfate, filtering again, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing by using a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 30:1, collecting effluent liquid according to actual gradient, performing TLC detection, combining the effluent liquid containing the product, distilling by using a rotary evaporator to remove the solvent, and performing vacuum drying to obtain a red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with the yield of 72 mg of 30.2.
The specific embodiment is thirty-six: 41.3 mg (0.2mmol) of (2-chloro-3, 3, 3-trifluoroprop-1-en-1-yl) benzene, 5.6 mg of cuprous bromide (20 mmol%), 1.0 eq 51.2 mg S89.3 mg of tetramethylethylenediamine (4)0% mmol), 130.0 mg cesium carbonate, in 2mL solvent N, N-dimethylformamide. Reacting for 12 hours at 120 ℃, cooling after the reaction is finished, and filtering the reaction solution to obtain filtrate; extracting the filtrate twice with saturated sodium chloride solution, performing back extraction once, drying the separated organic phase with anhydrous sodium sulfate, performing secondary filtration, performing rotary evaporation on the filtrate to remove the solvent to obtain a residue, performing silica gel column chromatography on the residue, performing drip washing with a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1, collecting effluent according to actual gradient, performing TLC detection, combining the effluent containing the product, distilling with a rotary evaporator to remove the solvent, and performing vacuum drying to obtain a red solid 5-phenyl 3H-1, 2-disulfide-3-thioketone with a yield of 28.6 mg of 68%.
In the embodiment of the invention, a compound containing 2-chloro-3, 3, 3-trifluoro-1-propene is used as a substrate to react with 1.0-1.5 equivalent of elemental sulfur, the molar range of cuprous bromide is 10-20%, a ligand is 20-40% of tetramethylethylenediamine, an alkali is cesium carbonate, and a solvent is based on N, N-dimethylformamide. Wherein examples one to seventeen are variable with differently substituted phenyl groups. It is noted that substituents on the phenyl group that are strongly electron withdrawing can also be advantageously used with the process of the present invention; examples eighteen to twenty-one are variable with the substituent R being naphthyl and heterocyclyl; examples twenty-two to twenty-five use copper salts of catalysts as variables; examples twenty-six to twenty-seven with ligands as variables; examples twenty eight to twenty nine with bases as variables; examples thirty to thirty-two with solvent as a variable; examples thirty-three to thirty-four with temperature as a variable; examples thirty-five to thirty-six were varied in the amount of elemental sulfur.
The reaction equation of the invention is as follows:
the reaction mechanism of the present invention is described in detail with reference to fig. 1:
first, S8The dissociation reaction occurs under the alkaline condition, and SO is generated3 2-And S2-，S2-May be further combined with S8The reaction produces polysulfides containing-S-. Then, the user can use the device to perform the operation,a compound containing 2-chloro-3, 3, 3-trifluoro-1-propene (hereinafter referred to as substrate 1) can remove one molecule of Cl under the action of alkali to generate HCl, and a double bond in the substrate 1 is changed into a triple bond, so that a trifluoropropyne derivative is formed, and the trifluoropropyne derivative and S are reacted to form a compound containing 2-chloro-3, 3, 3-trifluoro-1-propene2-Under the action of catalyst, one fluorine will be removed to produce intermediate A. Then, one fluorine in the intermediate A can be continuously removed to form a thioacyl fluoride active species B, and the thioacyl fluoride active species B reacts with S through the action of a catalyst2-Carrying out oxidation addition and polysulfide ligand exchange to obtain an intermediate C, and carrying out reduction elimination on the intermediate C to remove CuBr to obtain D; finally, under the influence of intramolecular nucleophilic action, sulfide and triple bond are subjected to ring combination to generate protonation, and a cyclization product 2 is formed.
According to the invention, the target product 1, 2-dithio-3-thioketone derivative can be directly synthesized, an intermediate product does not need to be separated, and the target product can be obtained only by stirring and reacting under normal pressure; the compound containing 2-chloro-3, 3, 3-trifluoro-1 propylene and the sulfur simple substance are used as raw materials, reactants are easy to obtain, and the preparation cost is low; in addition, by adding alkali and ligand into the system, the reaction temperature is controlled to be 80-120 ℃, the reaction time is 12 hours, the yield can be greatly improved and can reach 88 percent to the maximum, the process engineering is greatly simplified, the energy consumption is reduced, and the method has the advantage of high yield; in addition, the waste solution is less in the reaction process, and other polluted gases and liquid are not discharged, so that the method reduces the discharge of the waste solution, and has the advantages of protecting the environment and ensuring the health of operators; in addition, a series of 5-phenyl substituted 1, 2-dithio-3-thioketone derivatives can be prepared, and the method has strong substrate universality. Thus, the invention fills the blank of the method for preparing the 5-substituted 1, 2-dithiol-3-thioketone derivative at the present stage, promotes the development of the polysubstituted 1, 2-dithiol-3-thioketone derivative, provides powerful guarantee for developing the medicament containing the 1, 2-dithiol-3-thioketone derivative and provides reference for the conversion of fluoride into sulfide.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.
Claims (7)
1. A preparation method of 1, 2-dithio-3-thioketone derivatives synthesized by copper catalysis is characterized in that: the molecular formula of the 1, 2-disulfide-3-thione derivative is as follows:the catalyst is prepared by reacting 2-chloro-3, 3, 3-trifluoro-1-propylene compound and sulfur simple substance in a reaction system containing ligand and alkali under the action of a catalyst; the molecular formula of the 2-chloro-3, 3, 3-trifluoro-1-propylene compound is as follows:
wherein R is any one of phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2, 4-dimethylphenyl, 4-ethylbenzene, 3-methoxyphenyl, 4-thiomethylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 4-phenoxyphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 2-methyl-3-fluorophenyl, 4-trifluoromethylphenyl, 1-naphthyl, 2-thienyl, 2-furyl;
the catalyst is any one of cuprous bromide, cuprous acetate, cuprous chloride and cuprous iodide;
the ligand is any one of tetramethylethylenediamine, 1,10 phenanthroline and bipyridine;
the alkali is any one of cesium carbonate and potassium phosphate.
2. The method of claim 1, 2-dithio-3-thione derivatives, comprising the steps of: the reaction temperature is 80-120 ℃, and the reaction time is 12 h.
3. The method of claim 2, wherein the copper-catalyzed synthesis of the 1, 2-dithio-3-thione derivative is as follows: the whole reaction is carried out in a solvent, wherein the solvent is any one of N, N-dimethylformamide, acetonitrile and dimethyl sulfoxide.
4. The method of claim 3, wherein the copper-catalyzed synthesis of the 1, 2-dithio-3-thione derivative comprises: during the reaction, the molar parts of the substances added are as follows:
1 part of 2-chloro-3, 3, 3-trifluoro-1 propylene compound;
0.1-0.2 part of catalyst;
2 parts of alkali;
0.2-0.4 part of ligand;
1-1.5 parts of elemental sulfur.
5. The method of claim 4, wherein the copper-catalyzed synthesis of the 1, 2-dithio-3-thione derivative is as follows: after the reaction of the 2-chloro-3, 3, 3-trifluoro-1 propylene compound and the elemental sulfur is finished, a filtering and purifying process is carried out, wherein the filtering and purifying process comprises the following steps: filtering, extracting, drying the organic phase, filtering, evaporating, carrying out silica gel column chromatography, and finally carrying out vacuum concentration on the eluted effluent to obtain the product.
6. The method of claim 5, wherein the copper-catalyzed synthesis of the 1, 2-dithio-3-thione derivative comprises: the extract is a saturated sodium chloride solution.
7. The method of claim 6, wherein the copper-catalyzed synthesis of the 1, 2-dithio-3-thione derivative comprises: when the silica gel column chromatography is carried out, the eluent is a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of the mixed solution is 30: 1.
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| DE3636157A1 (en) * | 1986-10-24 | 1988-04-28 | Basf Ag | New methylenedithiolenequinone dyes, and thin, radiation-sensitive coating films containing them |
| CN102807557A (en) * | 2012-08-21 | 2012-12-05 | 苏州大学 | 3H-1,2-dithio-cyclopentene-3-thioketone compound and application thereof |
| CN102993166A (en) * | 2012-12-13 | 2013-03-27 | 苏州大学 | Preparation method and application of 3H-1,2-dithiole-3-thioketone compound |
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| DE3636157A1 (en) * | 1986-10-24 | 1988-04-28 | Basf Ag | New methylenedithiolenequinone dyes, and thin, radiation-sensitive coating films containing them |
| CN102807557A (en) * | 2012-08-21 | 2012-12-05 | 苏州大学 | 3H-1,2-dithio-cyclopentene-3-thioketone compound and application thereof |
| CN102993166A (en) * | 2012-12-13 | 2013-03-27 | 苏州大学 | Preparation method and application of 3H-1,2-dithiole-3-thioketone compound |
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