CN110272370B - Synthesis method of trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound - Google Patents
Synthesis method of trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound Download PDFInfo
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Abstract
The invention belongs to the technical field of chemical synthesis of organic fluorine, and relates to a method for synthesizing a trifluoromethyl-substituted 3,3 '-bis (2-phenylindolyl) methane compound, which takes 2-phenylindole as a substrate, trifluoroacetyl hydrazine as a fluoroalkyl source, under the action of a Cu catalyst, di-tert-butyl peroxide DTBP or dicumyl peroxide as an oxidant, potassium tert-butoxide, lithium tert-butoxide or potassium methoxide as an alkali, magnesium trifluoromethanesulfonate or silver trifluoromethanesulfonate as Lewis acid, and 1, 2-dichloroethane DCE as a solvent, the trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound is synthesized in one step. The synthesis method has the advantages of simple and convenient operation, cheap and easily obtained raw materials, diversified products and the like.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis of organic fluorine, and particularly relates to a method for synthesizing a trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound.
Background
Indole is an important benzo five-membered heterocyclic compound, wherein the bisindolylmethane derivative has rich physiological activity, and has the activities of resisting bacteria and fungi, resisting fibromyalgia, treating acute enteritis, promoting metabolism of estrogen in a human body, resisting cancer and the like. The trifluoromethyl group is introduced into the bis (indolyl) methane molecule, so that the physical, chemical and biological properties of the molecule can be greatly changed, the fat solubility is enhanced, the bioavailability is improved and the like, and the biological activity different from that of non-fluorine molecules is possibly shown. The prior literature reports that the method for synthesizing the bis-indole methane derivatives mainly adopts a condensation reaction catalyzed by Lewis or Bronsted acid or synthesizes from indole and carbonyl compounds, but all have the defects of expensive reagents which are difficult to prepare, extreme reaction conditions, complicated steps, narrow application range, low regioselectivity and the like. The invention relates to a method for synthesizing a trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound in one step by utilizing the reaction of readily available trifluoroacetyl hydrazine and 2-phenylindole.
Disclosure of Invention
The invention aims to provide a method for synthesizing a trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound, which has the advantages of simple and convenient operation, cheap and easily obtained raw materials, diversified products and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing a trifluoromethyl-substituted 3,3 '-bis (2-phenylindolyl) methane compound comprises the steps of taking 2-phenylindole as a substrate, taking trifluoroacetyl hydrazine as a fluoroalkyl source, taking di-tert-butyl peroxide DTBP or dicumyl peroxide as an oxidant, taking potassium tert-butoxide, lithium tert-butoxide or potassium methoxide as a base, taking magnesium trifluoromethanesulfonate or silver trifluoromethanesulfonate as Lewis acid, and taking 1, 2-dichloroethane DCE as a solvent under the action of a Cu catalyst, and synthesizing the trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound in one step.
Further, the Cu-based catalyst is Cu 2 S、CuCN、Cu 2 And (I) one of the compositions.
Further, of the two lewis acids, the isolation yield was higher when prepared using magnesium trifluoromethanesulfonate.
Further, it is based on 2-phenylindole as a substrate, trifluoroacetyl hydrazine as a fluoroalkyl source, in Cu 2 S is used as a catalyst, potassium tert-butoxide is used as a base, magnesium trifluoromethanesulfonate is used as Lewis acid, and di-tert-butyl peroxide (DTBP) is used as an oxidant to obtain a trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound; the reaction formula is as follows:
further, the 2-phenylindole substrate is any one of the following formulae 1 to 20:
further, the trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound is any one of the following formulae 1 to 20:
the specific steps of the synthesis method of the trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound are as follows: placing a mixture of 2-phenylindole, trifluoroacetyl hydrazine, potassium tert-butoxide, di-tert-butyl peroxide (DTBP), magnesium trifluoromethanesulfonate and cuprous sulfide in a reactor provided with a magnetic stirrer, adding a solvent, reacting at 120 ℃ for 12 hours, diluting the reaction mixture with ethyl acetate, and diluting with saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtering and removing the solvent by rotary evaporation, purifying through a silica gel column to obtain the trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound.
Furthermore, the molar ratio of the 2-phenylindole, trifluoroacetyl hydrazine, potassium tert-butoxide, di-tert-butylperoxide (DTBP), magnesium trifluoromethanesulfonate, cuprous sulfide and solvent is (0.2-0.5): (0.24-0.27): (0.8-1.0): (0.3-0.5): (0.24-0.27): 0.05-0.1): 300-900.
The invention has the beneficial effects that:
the invention uses simple and easily obtained 2-phenyl indole and trifluoroacetyl hydrazine as a fluoroalkyl source in Cu 2 S is used as a catalyst, potassium tert-butoxide is used as a base, di-tert-butyl peroxide (DTBP) is used as an oxidant, magnesium trifluoromethanesulfonate is used as a Lewis acid, the trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound is synthesized, the adaptability of the functional group is good, the operation is simple and convenient, the raw materials are cheap and easy to obtain, and the productDiversification and the like.
Drawings
FIG. 1 is a single crystal structural diagram of trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane obtained in example 1.
Detailed Description
In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.
Example 1
Under the protection of nitrogen, 0.2mmol of 2-phenylindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2-phenyl-1H-indole) (isolated yield 95%). 1 H NMR(400MHz,DMSO)δ11.44(s,2H),7.78(d,J＝8.1Hz,2H),7.43–7.24(m,8H),7.14(dd,J＝19.5,7.5Hz,6H),7.00(t,J＝7.5Hz,2H),5.57(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.9(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),136.34(s),132.7(s),132.74(s),129.34(s),128.8(s),128.6(q,J＝280.7Hz),128.5(s),126.9(s),121.6(s),120.7(s),119.7(s),111.9(s),106.5(s),δ39.59(q,J＝29.2Hz).
Example 2
Under the protection of nitrogen, 0.2mmol of 2- (4-bromophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate was added last1-2mL of 1, 2-dichloroethane as a solvent is stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then the reaction mixture is cooled to room temperature, diluted by ethyl acetate and saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-bromophenyl) -1H-indole) (isolated yield 71%) by column chromatography on silica gel. 1 H NMR(400MHz,DMSO)δ11.71(s,2H),7.76(s,2H),7.35(d,J＝8.0Hz,3H),7.33–7.27(m,4H),7.25(d,J＝8.4Hz,3H),7.15(d,J＝7.0Hz,4H),5.50(dd,J＝22.7,11.4Hz,1H). 19 F NMR(376MHz,DMSO)δ-62.1(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ139.9(s),134.8(s),131.9(s),129.3(s),128.9(s),128.4(s),128.2(q,J＝280.6Hz),124.3(s),122.5(s),113.9(s),112.5(s),105.7(s),δ39.43(q,J＝29.3Hz).
Example 3
Under the protection of nitrogen, 0.2mmol of 2- (4-methylphenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (p-tolyl) -1H-indole) which was isolated by column chromatography on silica (86% isolated yield). 1 H NMR(400MHz,DMSO)δ11.34(s,2H),7.81(d,J＝8.0Hz,2H),7.35(d,J＝7.9Hz,2H),7.15–6.94(m,12H),5.59(q,J＝11.6Hz,1H),2.36(s,6H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.8Hz,3F). 13 C NMR(101MHz,DMSO)δ138.4(s),137.76(s),136.2(s),129.8(s),129.4(s),129.0(s),128.7(q,J＝280.3Hz),126.8(s),121.5(s),120.7(s),119.6(s),111.8(s),106.4(s),21.3(s),δ39.41(q,J＝29.2Hz).
Example 4
Under the protection of nitrogen, 0.2mmol of 2- (4-chlorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-chlorophenyl) -1H-indole) (isolated yield 76%) by column chromatography on silica. 1 H NMR(400MHz,DMSO)δ11.44(s,2H),7.83(d,J＝8.0Hz,2H),7.35(d,J＝8.0Hz,2H),7.30(d,J＝7.8Hz,2H),7.19–7.08(m,3H),7.02(t,J＝7.4Hz,1H),5.58(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.5(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ136.8(s),136.4(s),133.5(s),131.2(s),130.8(s),128.8(s),128.7(q,J＝280.9Hz),126.5(s),121.9(s),120.8(s),119.9(s),112.0(s),107.1(s),δ39.32(q,J＝30.0Hz).
Example 5
Under the protection of nitrogen, 0.2mmol of N-methyl-2-phenylindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtering and removing the solvent by rotary evaporation, eluting with N-pentane and ethyl acetate, separating by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (N-methyl-2-phenyl-indole) (isolated product)Rate 65%). 1 H NMR(400MHz,DMSO)δ7.69(d,J＝8.1Hz,2H),7.48(t,J＝7.3Hz,4H),7.37(s,4H),7.19(t,J＝7.6Hz,2H),7.02(t,J＝7.5Hz,2H),6.49(d,J＝75.5Hz,2H),5.10(q,J＝11.7Hz,1H),3.42(s,8H). 19 F NMR(376MHz,DMSO)δ-62.9(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ140.7(s),136.9(s),131.2(s),130.9(s),129.2(d,J＝7.7Hz),128.2(q,J＝281.0Hz),126.1(s),121.8(s),120.5(s),120.1(s),110.6(s),106.5(s),30.9(s),δ39.42(q,J＝29.2Hz).
Example 6
Under the protection of nitrogen, 0.2mmol of 2- (4-fluorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-fluorophenyl) -1H-indole) which was isolated by column chromatography on silica gel (isolated yield 72%). 1 H NMR(400MHz,DMSO)δ11.43(s,2H),7.83(d,J＝5.0Hz,2H),7.35(d,J＝5.7Hz,2H),7.10(dd,J＝33.9,27.5Hz,12H),5.52(d,J＝10.2Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.7(d,J＝10.7Hz,3F),-113.68(s,1F). 13 C NMR(101MHz,DMSO)δ162.4(d,J＝245.6Hz),137.2(s),136.3(s),131.3(d,J＝8.4Hz),128.9(d,J＝3.0Hz),128.7(q,J＝280.8Hz),126.5(s),121.8(s),120.7(s),119.8(s),115.8(d,J＝21.6Hz),111.9(s),106.8(s),δ39.40(q,J＝30.3Hz).
Example 7
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-bromo-indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of trifluoromethaneAdding 1-2mL of 1, 2-dichloroethane as a solvent into magnesium sulfonate, stirring the mixture in a closed system under the condition of oil bath at 120 ℃ for 12 hours, cooling the mixture to room temperature, diluting the reaction mixture with ethyl acetate, and using saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-bromo-2-phenyl-1H-indole) (isolated yield 83%). 1 H NMR(400MHz,DMSO)δ11.43(s,2H),7.81(d,J＝8.0Hz,2H),7.44(d,J＝7.7Hz,4H),7.35(d,J＝8.0Hz,2H),7.13(d,J＝7.2Hz,2H),7.08(t,J＝7.7Hz,4H),7.01(t,J＝7.5Hz,2H),5.57(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.4(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ136.8(s),136.41(s),131.8(s),131.55(s),131.0(s),128.7(d,J＝280.3Hz),126.5(s),122.2(s),122.0(s),120.75(s),119.9(s),112.0(s),107.1(s),δ39.32(q,J＝29.9Hz).
Example 8
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-chloro-indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-chloro-2-phenyl-1H-indole) (isolated yield 83%). 1 H NMR(400MHz,DMSO)δ11.70(s,2H),7.59(s,2H),7.36(t,J＝9.2Hz,4H),7.28(d,J＝6.9Hz,4H),7.14(d,J＝7.2Hz,6H),5.52(q,J＝11.3Hz,1H). 19 F NMR(376MHz,DMSO)δ-62.2(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ140.1(s),134.7(s),132.0(s),129.3(s),128.9(s),128.2(q,J＝282.7Hz),127.8(s),124.5(s),121.8(s),119.5(s),113.5(s),105.9(s),δ39.42(q,J＝29.4Hz).
Example 9
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-fluoro-indole, 0.24mmol of trifluoroacethydrazide, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-fluoro-2-phenyl-1H-indole) (isolated yield 95%). 1 H NMR(400MHz,DMSO)δ11.64(s,2H),7.41(dd,J＝8.1,5.1Hz,2H),7.38–7.32(m,4H),7.29(t,J＝7.2Hz,4H),7.16(d,J＝7.4Hz,4H),7.02(t,J＝8.9Hz,2H),5.56(q,J＝11.4Hz,1H). 19 F NMR(376MHz,DMSO)δ-62.2(d,J＝11.6Hz,3F),-123.7(td,J＝10.5,5.2Hz,1F). 13 C NMR(101MHz,DMSO)δ158.6(s),156.3(s),140.4(s),133.0(s),132.3(s),129.3(s),128.8(d,J＝10.9Hz),128.4(q,J＝279.7Hz),127.0(d,J＝10.2Hz),113.0(d,J＝10.0Hz),110.0(d,J＝26.0Hz),106.4(s),105.1(d,J＝25.2Hz),δ39.19(d,J＝29.4Hz).
Example 10
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-methylindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtering and removing the solvent by rotary evaporation to obtain n-pentaneThe 3,3' - (2,2, 2-trifluoroethyl) bis (5-methyl-2-phenyl-1H-indole) was isolated by silica gel column chromatography using an eluent of an alkane and ethyl acetate (isolated yield 83%). 1 H NMR(400MHz,DMSO)δ11.30(s,2H),7.58(s,2H),7.32(d,J＝7.8Hz,5H),7.25(d,J＝13.5Hz,5H),6.96(d,J＝7.7Hz,2H),5.53(dd,J＝22.2,10.8Hz,12H),2.33(s,6H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),134.7(s),133.0(s),129.5(s),128.9(s),128.6(d,J＝278.2Hz),128.4(s),127.7(s),127.2(s),123.2(s),120.7(s),111.5(s),106.2(s),21.9(s),δ39.44(d,J＝29.8Hz).
Example 11
Under the protection of nitrogen, 0.2mmol of 2-naphthyl indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (naphthyl-di) -1H-indole) (isolated yield 91%). 1 H NMR(400MHz,DMSO)δ11.49(s,2H),7.82(d,J＝8.0Hz,2H),7.70(d,J＝8.0Hz,2H),7.59(s,2H),7.50(t,J＝7.1Hz,3H),7.47–7.35(m,7H),7.12(dd,J＝14.9,7.7Hz,4H),7.01(t,J＝7.5Hz,2H),5.82(q,J＝11.4Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.8Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),136.5(s),132.8(s),132.6(s),130.1(s),128.3(s),128.2(s),128.1(s),127.9(s),126.9(s),126.8(s),126.7(d,J＝1.9Hz),126.0(d,J＝280.4Hz),121.8(s),120.8(s),119.8(s),111.9(s),107.1(s),δ39.42(q,J＝29.8Hz).
Example 12
Adding into a 25mL reaction tube with a polytetrafluoroethylene magnetic stirrer in a nitrogen protective atmosphere0.2mmol of 2- (3, 5-dimethylphenyl) indole, 0.24mmol of trifluoroacethydrazide, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butylperoxide (DTBP), 0.05mmol of Cu 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (3, 5-dimethylphenyl) -1H-indole) (isolated yield 71%). 1 H NMR(400MHz,DMSO)δ11.30(s,2H),7.68(d,J＝7.6Hz,2H),7.34(d,J＝7.7Hz,2H),7.09(t,J＝7.0Hz,2H),7.00–6.93(m,2H),6.92(s,2H),6.70(s,4H),5.59(dd,J＝22.7,11.2Hz,1H),2.17(s,12H). 19 F NMR(376MHz,DMSO)δ-61.9(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ138.5(s),137.5(s),136.2(s),132.6(s),129.8(s),128.6(q,J＝280.6Hz),127.0(s),126.9(s),121.4(s),120.5(s),119.6(s),111.7(s),106.5(s),21.4(s),δ39.41(q,J＝29.6Hz).
Example 13
Under the protection of nitrogen, 0.2mmol of 2- (4-methylphenyl) -5-chloroindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (5-chloro-2- (4-methylphenyl) -1H-indole) (isolated yield 78%) by column chromatography on silica. 1 H NMR(400MHz,DMSO)δ11.62(s,2H),7.63(s,2H),7.37(d,J＝8.6Hz,2H),7.13(d,J＝8.6Hz,2H),7.07(d,J＝7.8Hz,4H),7.02(d,J＝7.7Hz,4H),5.55(q,J＝11.6Hz,1H),2.35(s,6H). 19 F NMR(376MHz,DMSO)δ-62.0(d,J＝11.8Hz,3F). 13 C NMR(101MHz,DMSO)δ140.2(s),138.3(s),135.4–134.7(m),129.4(s),129.1(s),129.1(s),128.4(q,J＝280.7Hz),127.8(s),124.4(s),121.6(s),119.5(s),113.4(s),105.9(s),21.3(s),δ39.41(q,J＝29.0Hz).
Example 14
Under the protection of nitrogen, 0.2mmol of 2- (4-fluorophenyl) -5-chloroindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (3-fluorophenyl) -1H-indole) (isolated yield 63%) which was isolated by column chromatography on silica. 1 H NMR(400MHz,DMSO)δ11.48(s,2H),7.80(d,J＝8.1Hz,2H),7.37(d,J＝8.0Hz,2H),7.30(dd,J＝14.5,7.3Hz,2H),7.13(t,J＝7.7Hz,4H),7.02(d,J＝6.8Hz,4H),6.90(d,J＝9.8Hz,2H),5.62(q,J＝11.6Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.6(d,J＝11.7Hz,3F),-112.4(dd,J＝15.8,9.1Hz,1F). 13 C NMR(101MHz,DMSO)δ162.2(d,J＝244.3Hz),136.5(d,J＝34.4Hz),134.7(d,J＝8.3Hz),130.8(d,J＝8.7Hz),128.6(q,J＝280.6Hz),126.0(d,J＝128.2Hz),121.0(d,J＝209.7Hz),120.8(s),116.0(d,J＝22.1Hz),115.4(d,J＝20.9Hz),112.0(s),107.2(s),δ39.33(q,J＝29.5Hz).
Example 15
Under the protection of nitrogen, 0.2mmol of 2- (3-fluorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of trifluoromethanesulfonic acidAdding 1-2mL of 1, 2-dichloroethane as a solvent into magnesium, stirring the mixture in a closed system under the condition of oil bath at 120 ℃ for 12 hours, cooling the mixture to room temperature, diluting the reaction mixture with ethyl acetate, and using saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-chloro-2- (4-fluorophenyl) -1H-indole) (isolated yield 61%). 1 H NMR(400MHz,DMSO)δ11.61(s,2H),7.36(d,J＝11.8Hz,4H),7.29(d,J＝7.6Hz,4H),7.12(d,J＝7.7Hz,4H),7.00(t,J＝9.0Hz,2H),5.55(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.7(d,J＝11.6Hz,3F),-123.6(td,J＝10.0,4.9Hz,1F). 13 C NMR(101MHz,DMSO)δ157.5(d,J＝231.5Hz),138.9(s),133.4(d,J＝79.3Hz),130.7(d,J＝4.8Hz),128.8(s),128.4(q,J＝280.3Hz),126.6(d,J＝10.2Hz),113.1(d,J＝9.9Hz),110.3(d,J＝26.1Hz),107.0(s),105.0(d,J＝25.1Hz),δ39.32(q,J＝30.2Hz).
Example 16
Under the protection of nitrogen, 0.2mmol of 2- (3-methoxyphenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (3-methoxyphenyl) -1H-indole) (isolated yield 76%). 1 H NMR(400MHz,DMSO)δ11.40(s,2H),7.79(d,J＝7.5Hz,2H),7.37(d,J＝7.5Hz,2H),7.23–7.15(m,2H),7.14–7.05(m,2H),7.00(t,J＝6.8Hz,2H),6.87(d,J＝7.6Hz,2H),6.75(d,J＝6.9Hz,2H),6.69(s,2H),5.68(dd,J＝22.3,11.0Hz,1H),3.70(s,6H). 19 F NMR(376MHz,DMSO)δ-61.7(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ159.4(s),138.2(s),136.3(s),133.9(s),129.8(s),128.7(q,J＝280.7Hz),126.8(s),121.5(d,J＝31.8Hz),120.8(s),119.8(s),114.5(d,J＝38.3Hz),111.9(s),106.7(s),δ39.42(q,J＝30.3Hz).
Example 17
Under the protection of nitrogen, 0.2mmol of 2- (3-fluorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium methoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 I, adding 0.2mmol of magnesium trifluoromethanesulfonate into 1-2mL of 1, 2-dichloroethane as a solvent, stirring the mixture in a closed system under the condition of 120 ℃ oil bath for reaction for 12 hours, cooling the mixture to room temperature, diluting the reaction mixture with ethyl acetate, and adding saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (5-chloro-2- (4-fluorophenyl) -1H-indole) (isolated yield 42%) by column chromatography on silica gel. 1 H NMR(400MHz,DMSO)δ11.61(s,2H),7.36(d,J＝11.8Hz,4H),7.29(d,J＝7.6Hz,4H),7.12(d,J＝7.7Hz,4H),7.00(t,J＝9.0Hz,2H),5.55(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.7(d,J＝11.6Hz,3F),-123.6(td,J＝10.0,4.9Hz,1F). 13 C NMR(101MHz,DMSO)δ157.5(d,J＝231.5Hz),138.9(s),133.4(d,J＝79.3Hz),130.7(d,J＝4.8Hz),128.8(s),128.4(q,J＝280.3Hz),126.6(d,J＝10.2Hz),113.1(d,J＝9.9Hz),110.3(d,J＝26.1Hz),107.0(s),105.0(d,J＝25.1Hz),δ39.32(q,J＝30.2Hz).
Example 18
Under the protection of nitrogen, 0.2mmol of 2- (3, 5-dimethylphenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of lithium tert-butoxide, 0.3mmol of dicumyl peroxide and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of magnesium trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, and the reaction mixture is treated with ethyl acetateEster dilution with saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (3, 5-dimethylphenyl) -1H-indole) (isolated yield 52%). 1 H NMR(400MHz,DMSO)δ11.30(s,2H),7.68(d,J＝7.6Hz,2H),7.34(d,J＝7.7Hz,2H),7.09(t,J＝7.0Hz,2H),7.00–6.93(m,2H),6.92(s,2H),6.70(s,4H),5.59(dd,J＝22.7,11.2Hz,1H),2.17(s,12H). 19 F NMR(376MHz,DMSO)δ-61.9(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ138.5(s),137.5(s),136.2(s),132.6(s),129.8(s),128.6(q,J＝280.6Hz),127.0(s),126.9(s),121.4(s),120.5(s),119.6(s),111.7(s),106.5(s),21.4(s),δ39.41(q,J＝29.6Hz).
Example 19
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-methylindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of sodium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of CuCN and 0.2mmol of magnesium trifluoromethanesulfonate are added in a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 1-2mL of 1, 2-dichloroethane as a solvent is added in the reaction tube, the mixture is stirred in a closed system under the condition of 120 ℃ oil bath and reacts for 12 hours, then the reaction tube is cooled to room temperature, the reaction mixture is diluted by ethyl acetate and is treated by saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-methyl-2-phenyl-1H-indole) (isolated yield 61%). 1 H NMR(400MHz,DMSO)δ11.30(s,2H),7.58(s,2H),7.32(d,J＝7.8Hz,5H),7.25(d,J＝13.5Hz,5H),6.96(d,J＝7.7Hz,2H),5.53(dd,J＝22.2,10.8Hz,12H),2.33(s,6H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),134.7(s),133.0(s),129.5(s),128.9(s),128.6(d,J＝278.2Hz),128.4(s),127.7(s),127.2(s),123.2(s),120.7(s),111.5(s),106.2(s),21.9(s),δ39.44(d,J＝29.8Hz).
Example 20
Under the protection of nitrogen, 0.2mmol of 2- (4-methylphenyl) -5-chloroindole, 0.24mmol of trifluoroacethydrazide, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of CuOAc and 0.2mmol of magnesium trifluoromethanesulfonate are added in a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 1-2mL of 1, 2-dichloroethane is added in a closed system under the condition of oil bath at 120 ℃ for stirring reaction for 12 hours and then the reaction mixture is cooled to room temperature, the reaction mixture is diluted by saturated NaHCO ethyl acetate and is cooled to room temperature 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (5-chloro-2- (4-methylphenyl) -1H-indole) (isolated yield 78%) by column chromatography on silica. 1 H NMR(400MHz,DMSO)δ11.62(s,2H),7.63(s,2H),7.37(d,J＝8.6Hz,2H),7.13(d,J＝8.6Hz,2H),7.07(d,J＝7.8Hz,4H),7.02(d,J＝7.7Hz,4H),5.55(q,J＝11.6Hz,1H),2.35(s,6H). 19 F NMR(376MHz,DMSO)δ-62.0(d,J＝11.8Hz,3F). 13 C NMR(101MHz,DMSO)δ140.2(s),138.3(s),135.4–134.7(m),129.4(s),129.1(s),129.1(s),128.4(q,J＝280.7Hz),127.8(s),124.4(s),121.6(s),119.5(s),113.4(s),105.9(s),21.3(s),δ39.41(q,J＝29.0Hz).
Example 21
Under the protection of nitrogen, 0.2mmol of 2- (4-fluorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP) and 0.05mmol of CuF are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 0.2mmol of silver trifluoromethanesulfonate AgOTf is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation eluting with n-pentane and ethyl acetate gave 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-fluorophenyl) -1H-indole) which was isolated by column chromatography on silica gel (isolated yield 66%). 1 H NMR(400MHz,DMSO)δ11.43(s,2H),7.83(d,J＝5.0Hz,2H),7.35(d,J＝5.7Hz,2H),7.10(dd,J＝33.9,27.5Hz,12H),5.52(d,J＝10.2Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.7(d,J＝10.7Hz,3F),-113.68(s,1F). 13 C NMR(101MHz,DMSO)δ162.4(d,J＝245.6Hz),137.2(s),136.3(s),131.3(d,J＝8.4Hz),128.9(d,J＝3.0Hz),128.7(q,J＝280.8Hz),126.5(s),121.8(s),120.7(s),119.8(s),115.8(d,J＝21.6Hz),111.9(s),106.8(s),δ39.40(q,J＝30.3Hz).
Example 22
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-methylindole, 0.24mmol of trifluoroacethydrazide, 0.7mmol of potassium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of CuBr and 0.2mmol of AgOAc are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 1-2mL of 1, 2-dichloroethane as a solvent are added into the reaction tube, the mixture is stirred and reacted in a closed system under the condition of 120 ℃ oil bath for 12 hours, then the reaction tube is cooled to room temperature, the reaction mixture is diluted by ethyl acetate and is saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-methyl-2-phenyl-1H-indole) (isolated yield 75%). 1 H NMR(400MHz,DMSO)δ11.30(s,2H),7.58(s,2H),7.32(d,J＝7.8Hz,5H),7.25(d,J＝13.5Hz,5H),6.96(d,J＝7.7Hz,2H),5.53(dd,J＝22.2,10.8Hz,12H),2.33(s,6H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.5Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),134.7(s),133.0(s),129.5(s),128.9(s),128.6(d,J＝278.2Hz),128.4(s),127.7(s),127.2(s),123.2(s),120.7(s),111.5(s),106.2(s),21.9(s),δ39.44(d,J＝29.8Hz).
Example 23
Under the protection of nitrogen, 0.2mmol of 2-phenyl-5-fluoro-indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of dicumyl peroxide, 0.05mmol of CuSCN and 0.2mmol of magnesium trifluoromethanesulfonate are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and 1-2mL of 1, 2-dichloroethane as a solvent are added into the reaction tube, and the mixture is stirred and reacted in a closed system under the condition of 120 ℃ oil bathAfter 12h cooling to room temperature, the reaction mixture was diluted with ethyl acetate and saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (5-fluoro-2-phenyl-1H-indole) methane (isolated yield 83%). 1 H NMR(400MHz,DMSO)δ11.64(s,2H),7.41(dd,J＝8.1,5.1Hz,2H),7.38–7.32(m,4H),7.29(t,J＝7.2Hz,4H),7.16(d,J＝7.4Hz,4H),7.02(t,J＝8.9Hz,2H),5.56(q,J＝11.4Hz,1H). 19 F NMR(376MHz,DMSO)δ-62.2(d,J＝11.6Hz,3F),-123.7(td,J＝10.5,5.2Hz,1F). 13 C NMR(101MHz,DMSO)δ158.6(s),156.3(s),140.4(s),133.0(s),132.3(s),129.3(s),128.8(d,J＝10.9Hz),128.4(q,J＝279.7Hz),127.0(d,J＝10.2Hz),113.0(d,J＝10.0Hz),110.0(d,J＝26.0Hz),106.4(s),105.1(d,J＝25.2Hz),δ39.19(d,J＝29.4Hz).
Example 24
Under the protection of nitrogen, adding 0.2mmol of 2- (4-chlorophenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of lithium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of CuCl and 0.2mmol of magnesium trifluoromethanesulfonate into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally adding 1-2mL of 1, 2-dichloroethane as a solvent, stirring in an oil bath at 120 ℃ for reaction for 12 hours, cooling to room temperature, diluting the reaction mixture with ethyl acetate, and diluting with saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-chlorophenyl) -1H-indole) (isolated yield 65%). 1 H NMR(400MHz,DMSO)δ11.44(s,2H),7.83(d,J＝8.0Hz,2H),7.35(d,J＝8.0Hz,2H),7.30(d,J＝7.8Hz,2H),7.19–7.08(m,3H),7.02(t,J＝7.4Hz,1H),5.58(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.5(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ136.8(s),136.4(s),133.5(s),131.2(s),130.8(s),128.8(s),128.7(q,J＝280.9Hz),126.5(s),121.9(s),120.8(s),119.9(s),112.0(s),107.1(s),δ39.32(q,J＝30.0Hz).
Example 25
Under the protection of nitrogen, 0.2mmol of 2-phenylindole, 0.24mmol of trifluoroacetyl hydrazine, 0.7mmol of potassium tert-butoxide, 0.3mmol of dicumyl peroxide and 0.05mmol of Cu are added into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer 2 S, 0.2mmol of silver trifluoromethanesulfonate is finally added with 1-2mL of 1, 2-dichloroethane as a solvent, stirred and reacted in a closed system for 12 hours under the condition of 120 ℃ oil bath, then cooled to room temperature, the reaction mixture is diluted with ethyl acetate and saturated NaHCO is used 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtration and removal of the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, was separated by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2-phenyl-1H-indole) (isolated yield 87%). 1 H NMR(400MHz,DMSO)δ11.44(s,2H),7.78(d,J＝8.1Hz,2H),7.43–7.24(m,8H),7.14(dd,J＝19.5,7.5Hz,6H),7.00(t,J＝7.5Hz,2H),5.57(q,J＝11.5Hz,1H). 19 F NMR(376MHz,DMSO)δ-61.9(d,J＝11.7Hz,3F). 13 C NMR(101MHz,DMSO)δ138.2(s),136.34(s),132.7(s),132.74(s),129.34(s),128.8(s),128.6(q,J＝280.7Hz),128.5(s),126.9(s),121.6(s),120.7(s),119.7(s),111.9(s),106.5(s),δ39.59(q,J＝29.2Hz).
Example 26
Under the protection of nitrogen, adding 0.2mmol of 2- (4-methylphenyl) indole, 0.24mmol of trifluoroacetyl hydrazine, 0.8mmol of lithium tert-butoxide, 0.3mmol of di-tert-butyl peroxide (DTBP), 0.05mmol of CuCN and 0.2mmol of silver trifluoromethanesulfonate into a 25mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally adding 1-2mL of 1, 2-dichloroethane as a solvent, stirring in an oil bath at 120 ℃ for 12h, cooling to room temperature, diluting the reaction mixture with ethyl acetate, and using saturated NaHCO to react 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtering and removing the solvent by rotary evaporation, eluting with n-pentane and ethyl acetate, separating by column chromatography on silica gel to give 3,3' - (2,2, 2-trifluoroethyl) bis (2- (4-methylphenyl) -1H-indole) (isolated yield)79％)。 1 H NMR(400MHz,DMSO)δ11.34(s,2H),7.81(d,J＝8.0Hz,2H),7.35(d,J＝7.9Hz,2H),7.15–6.94(m,12H),5.59(q,J＝11.6Hz,1H),2.36(s,6H). 19 F NMR(376MHz,DMSO)δ-61.8(d,J＝11.8Hz,3F). 13 C NMR(101MHz,DMSO)δ138.4(s),137.76(s),136.2(s),129.8(s),129.4(s),129.0(s),128.7(q,J＝280.3Hz),126.8(s),121.5(s),120.7(s),119.6(s),111.8(s),106.4(s),21.3(s),δ39.41(q,J＝29.2Hz)。
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.
Claims (3)
1. A method for synthesizing trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound, characterized by: 2-phenylindole is used as a substrate, trifluoroacetyl hydrazine is used as a fluoroalkyl source, under the action of a Cu catalyst, di-tert-butyl peroxide DTBP or dicumyl peroxide is used as an oxidant, potassium tert-butoxide, lithium tert-butoxide or potassium methoxide is used as a base, magnesium trifluoromethanesulfonate or silver trifluoromethanesulfonate is used as Lewis acid, and 1, 2-dichloroethane DCE is used as a solvent, the trifluoromethyl-substituted 3,3' -bis (2-phenylindole) methane compound is synthesized in one step; the Cu catalyst is Cu 2 S、CuCN、Cu 2 One of I; the 2-phenylindole is any one of the following formulas 1 to 13:
2. the method for synthesizing a trifluoromethyl-substituted 3,3' -bis (2-phenylindolyl) methane compound according to claim 1, wherein: the specific synthesis steps are as follows: placing a mixture of 2-phenylindole, trifluoroacetyl hydrazine, potassium tert-butoxide, di-tert-butyl peroxide DTBP, magnesium trifluoromethanesulfonate and cuprous sulfide in a reactor provided with a magnetic stirrer, adding a solvent DCE, reacting at 120 ℃ for 12h, diluting the reaction mixture with ethyl acetate, and using saturated NaHCO 3 The solution was washed with saturated brine and the organic phase was washed with anhydrous MgSO 4 Drying, filtering and removing the solvent by rotary evaporation, purifying through a silica gel column to obtain the trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound.
3. The method of claim 2, wherein the step of synthesizing the trifluoromethyl substituted 3,3' -bis (2-phenylindolyl) methane compound comprises: the molar ratio of 2-phenylindole, trifluoroacetyl hydrazine, potassium tert-butoxide, di-tert-butyl peroxide DTBP, magnesium trifluoromethanesulfonate, cuprous sulfide and solvent DCE is (0.2-0.5): (0.24-0.27): (0.8-1.0): (0.3-0.5): (0.24-0.27): 0.05-0.1): 300-900.
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| CN103214408A (en) * | 2013-05-07 | 2013-07-24 | 南京理工大学 | Method for synthesizing bisindole methane derivative |
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| Convenient synthesis of α-trifluoromethyl amines via aminofluoroalkylation of arenes with N-trimethylsilyl α-trifluoroacetaldehyde hemiaminal;Yuefa Gong等;《Journal of Fluorine Chemistry》;20021231;第116卷(第2期);第103-107页 * |
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