CN104844410A - Synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds - Google Patents
Synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds Download PDFInfo
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Abstract
The invention discloses a synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds. The synthetic method enable tosylhydrazones and acetylene compounds of Alpha, alpha, alpha, 3 methyl ketone to react in organic solvent. 1, 1-2 fluorine - 1, 3 - acetylene compounds is obtained through the catalysis of cuprous CuX and the existing of soda and annexing agent. The synthetic method of 1, 1-2 fluorine - 1, 3 - acetylene compounds preferentially uses copper iodide which is cheap and stable as catalyst, and the operation is relatively convenient and easy. Also the copper iodide has good tolerance and universality to functional groups. The invention has the advantages that the raw materials are easy to obtain, the reaction cost is relative low, and the reaction time is relative short. The invention is suitable for the preparation of 1, 1-2 fluorine - 1, 3 - acetylene compounds.
Description
Technical field
The invention belongs to organic synthesis field, particularly relate to the synthetic method of fluoro-1, the 3-yne compounds of 1,1-bis-.
Background technology
Fluorine atom makes it in Materials science due to special chemical property, and life science and pharmacy field have consequence, and therefore how efficiently introducing fluorine-containing functional group just becomes the important directions that synthetic chemistry men study.Wherein, fluoro-1, the 3-yne compounds of 1,1-bis-is the more special yne compounds of a class, there is good application prospect.The method of traditional this compounds of synthesis is mainly: 1) utilize the building block containing two fluoroolefin and alkynes to carry out coupling synthesis, 2) utilize Wittig to react.But the practicality of these methods is lower, first synthesize the coupling building block with two fluoroolefin and inherently there is very large problem, needing to compare exacting terms, there is larger problem in functional group compatibility.Rear a kind of report utilizing Wittig to react is then little, only has an example report at present.
Summary of the invention
The object of this invention is to provide a kind of under comparatively gentle condition, the shorter reaction times synthesizes the method for fluoro-1, the 3-yne compounds of 1,1-bis-.The method, from raw material simple and easy to get, utilizes relatively cheap and stable cuprous salt to realize the efficient synthesis of fluoro-1, the 3-eneyne derivative of 1,1-bis-as catalyzer, has substrate universality comparatively widely.
The technical scheme of the inventive method is as follows:
The synthetic method of fluoro-1, the 3-yne compounds of a kind of 1,1-bis-, comprising:
Tosylhydrazone and the Terminal Acetylenes of α, α, α-trifluorumethylketone react in organic solvent, and under monovalence copper CuX catalysis, and when having alkali and additive to exist, generate fluoro-1, the 3-eneyne derivative of 1,1-bis-, its reaction formula is as follows:
Wherein: R
1represent aromatic base, heterocyclic aromatic base or alkyl; R
2represent aromatic base, heterocyclic aromatic base, thiazolinyl, alkyl or silica-based, described additive comprises tetrabutylammonium chloride or trifluoromethanesulfonic acid lithium.
Above-mentioned reaction has good tolerance to functional group, R
1when representing aromatic base, can be phenyl, substituted-phenyl or naphthyl, can with one or more substituting group on phenyl ring, described substituting group can be methyl, methoxyl group, nitro, trifluoromethyl or halogen (fluorine, chlorine, bromine, iodine); When phenyl ring has multiple substituting group, these substituting groups can be identical or different, and two adjacent substituting groups can separate or Cheng Huan.R
1when representing heterocyclic aromatic base, also can carry out compatibility well, such as thienyl, R
1when representing alkyl, described alkyl can be cyclohexyl or n-heptyl.
R
2when representing aromatic base, can be phenyl, substituted-phenyl or naphthyl, can with one or more identical or different substituting group on phenyl ring, described substituting group can be methyl, trifluoromethyl, methoxyl group, halogen (chlorine, bromine, iodine), ester group or N, N-dimethyl amido, when having multiple substituting group, this multiple substituting group can be identical or different, and two adjacent substituting groups can separate or Cheng Huan.R
2when representing heterocyclic aromatic base, can be thienyl or pyridyl.R
2when representing thiazolinyl, described thiazolinyl can be cyclohexenyl.R
2when representing alkyl, described alkyl can be normal-butyl, cyclopropyl, cyclohexyl, styroyl, 1,1-diethyl methylol; R
2when representing silica-based, described silica-based can be triisopropylsilyl.
Work as R
1for aromatic base, R
2during for phenyl, R
1substituent R on middle phenyl ring ' representing methyl, trifluoromethyl, methoxyl group, halogen (chlorine, bromine, iodine) and nitro, the reaction formula of the inventive method can be expressed as follows:
Work as R
1for naphthyl, R
2during for phenyl, the reaction formula of the inventive method can be expressed as follows:
Work as R
1during for heterocyclic aromatic base, heterocycle can be thienyl; R
2for phenyl, the reaction formula of the inventive method can be expressed as follows:
Work as R
1during for alkyl, alkyl can be n-heptyl and cyclohexyl; R
2for phenyl, the reaction formula of the inventive method can be expressed as follows:
Work as R
1for phenyl, R
2during for substituted-phenyl, the substituent R on phenyl ring " represent alkyl, trifluoromethyl, alkoxyl group, various halogen (chlorine, bromine, iodine), ester group and N, N-dimethyl amido, the reaction formula of the inventive method can be expressed as follows:
Work as R
1for phenyl, R
2during for naphthalene nucleus, the reaction formula of the inventive method can be expressed as follows:
Work as R
1for phenyl, R
2during for heterocyclic aromatic base, heterocycle can be thienyl and pyridyl, and the reaction formula of the inventive method can be expressed as follows:
Work as R
1for phenyl, R
2during for thiazolinyl, thiazolinyl can be cyclohexenyl, and the reaction formula of the inventive method can be expressed as follows:
Work as R
1during for phenyl; R
2for alkyl, alkyl can be chain-like alkyl (butyl, styroyl and 1-Hydroxy pentyl), cyclic alkyl (cyclopropyl, cyclohexyl).The reaction formula of the inventive method can be expressed as follows:
Work as R
1during for phenyl; R
2for silica-based, when silylation is triisopropylsilyl (abbreviation TIPS), the reaction formula of the inventive method can be expressed as follows:
The molar weight of the alkali that the inventive method uses can be 1.0 ~ 3.5 times of Terminal Acetylenes molar weight, salt of wormwood can be selected from, potassium tert.-butoxide, lithium hydroxide, cesium fluoride or trimethyl carbinol lithium, be preferably the trimethyl carbinol lithium of 2.0 times of molar weights (molar weight relative to alkynes).
The monovalence copper that the inventive method uses is selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous thiocyanate or four acetonitrile phosphofluoric acids cuprous in one or more, be preferably cuprous iodide; Consumption is 0.1-0.3 times of Terminal Acetylenes molar weight.0.2 times of preferred Terminal Acetylenes molar weight.
When the additive that the inventive method uses is for tetrabutylammonium chloride, consumption is 0.1 ~ 0.4 times of Terminal Acetylenes molar weight, is preferably 0.2 times of Terminal Acetylenes molar weight; When additive is trifluoromethanesulfonic acid lithium, consumption can be 1.0 ~ 2.0 times of Terminal Acetylenes molar weight, is preferably 1.0 times of Terminal Acetylenes molar weight, also both can be mixed use.
The organic solvent that the inventive method uses can be toluene, 1,2-ethylene dichloride, acetonitrile or Isosorbide-5-Nitrae-dioxane, be preferably 1,4-dioxane, need sodium Metal 99.5 to use after drying and distilling under nitrogen atmosphere, its consumption is 5 ~ 20mL/mmol Terminal Acetylenes (namely every mmole Terminal Acetylenes uses 5 ~ 20mL organic solvent), is preferably 15mL/mmol Terminal Acetylenes.
The Tosylhydrazone of the inventive method α, α, α-trifluorumethylketone and the molar ratio example of Terminal Acetylenes can be 1.0:1.0 ~ 2.0:1.0, are preferably 1.0:1.0.
The preferred temperature of reaction of the inventive method is between 40 ~ 110 DEG C, is preferably 60 DEG C;
Reaction times of the present invention is 1 ~ 4 hour, is preferably 2 hours.
The present invention preferably carries out aftertreatment to reaction product after completion of the reaction, comprises the core post by 10mL, concentrated and purifying.
Described concentration process can adopt underpressure distillation, such as, use Rotary Evaporators concentrating under reduced pressure.
Described purge process obtains pure product by column chromatography.
Compared to the prior art, the present invention has following advantage:
1, the present invention uses comparatively stable and cheap cuprous salt, and preferred cuprous iodide is as catalyzer.
2, the reactant involved by the inventive method has good universality, and the substituting group on the carbon of hydrazone can be aromatic base, assorted aromatic base, chain-like alkyl, and cyclic alkyl.One end substituting group of Terminal Acetylenes can be aromatic base, assorted aromatic base, cyclic alkenyl radical, chain-like alkyl, cyclic alkyl, and silylation alkynes.The functional group of substrate has good compatibility, can be aryl, alkyl, various halogen, trifluoromethyl, alkoxyl group, ester group, nitro, hydroxyl, and N, N-dimethyl amido etc.
The efficiency of the reaction 3, involved by the inventive method is higher, and condition is gentleer, and the raw material of reaction is relatively stable to be easy to get.
Embodiment
The present invention is further described below in conjunction with embodiment, but the scope do not limited the present invention in any way.
In following examples, the reagent used directly buys use, uses after the drying of portion of reagent purifying.
Embodiment 1
2,4-phenylbenzene 1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, the Tosylhydrazone 68mg (0.2mmol) of 1,1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), appropriate additive, nitrogen substitutes gas, then adds 3mL 1,4-dioxane, adds phenylacetylene 20mg (0.2mmol) under stirring.Electromagnetic Heating agitator reacts about 2 hours at a certain temperature.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtains 2,4-phenylbenzene 1 by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
For this reaction, when other conditions are constant, by adjustment additive, temperature of reaction, alkali, hydrazone and cupprous kind or reacting weight, study its impact on productive rate, what obtain the results are shown in following table:
This compound is weak yellow liquid, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.62-7.60(m,2H),7.51-7.50(m,2H),7.40-7.37(m,2H),7.35-7.33(m,4H)；
13C NMR(100MHz,CDCl
3)δ159.1(dd,J＝297.7Hz,J＝303.1Hz),131.6,130.7(d,J＝6.4Hz),128.63,128.60,128.4,127.9,127.8(dd,J＝3.5Hz,J＝5.4Hz),122.8,94.4(t,J＝5.4Hz),82.4(dd,J＝20.3Hz,J＝27.4Hz),81(dd,J＝4.1Hz,J＝8.2Hz)；
19F NMR(376MHz,CDCl
3)δ-74.9(d,J＝4.5Hz,1F),-79.5(d,J＝4.2Hz,1F)。
Embodiment 2
The fluoro-1-alkene-3-alkynes of 2-(4 '-fluorophenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 72mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-fluorophenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-fluorophenyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 47%, and its nuclear magnetic data is as follows:
1hNMR (400MHz, CDCl
3) δ 7.58 (dd, J=5.4Hz, 2H), 7.51-7.49 (m, 2H), 7.35-7.33 (m, 3H), 7.09 (t, J=8.6Hz, 2H);
13c NMR (100MHz, CDCl
3) δ 162.2 (d, J=248.2Hz), 159.0 (dd, J=298Hz, J=302.4Hz), 131.5,129.7-129.5 (m, 1C), 128.7,128.4,128.3 (d, J=151.2Hz), 122,6,115.6 (d, J=21.7Hz), 94.6 (t, J=6.0Hz), 81.7 (dd, J=21.4Hz, J=28.0Hz), 80.2 (dd, J=4.5Hz, J=7.9Hz);
19f NMR (376MHz, CDCl
3) δ-77.6 (d, J=8.5Hz, 1F) ,-81.7 (d, J=8.7Hz) ,-114.8 (s, 1F).
Embodiment 3
The fluoro-1-alkene-3-alkynes of 2-(4 '-chloro-phenyl-)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 75mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-chloro-phenyl-) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-chloro-phenyl-)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 66%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.55-7.49(m,4H),7.37-7.34(m,5H)；
13C NMR(100MHz,CDCl
3)δ159.1(dd,J＝298.3Hz,J＝303.4Hz),133.8,131.6,129.2(dd,J＝1.8Hz,J＝6.6Hz),129.1(dd,J＝3.5Hz,J＝6.0Hz),128.8,128.4,127.7,122.5,94.8(t,J＝6.0Hz),81.8(dd,J＝21.5Hz,J＝27.6Hz),79.9(dd,J＝4.4Hz,J＝7.7Hz)；
19F NMR(376MHz,CDCl
3)δ-74.3(d,J＝2.7Hz),-78.9(d,2.7Hz)。
Embodiment 4
The fluoro-1-alkene-3-alkynes of 2-(4 '-bromophenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 84mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-bromophenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-bromophenyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 63%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.53-7.46(m,6H),7.35-7.33(m,3H)；
13C NMR(100MHz,CDCl
3)δ159.1(dd,J＝298.5Hz,J＝303.6Hz,131.8,131.6,129.7(dd,J＝1.6Hz,J＝6.3Hz),129.3(dd,J＝3.4Hz,J＝6.2Hz),128.8,128.4,122.5,122.0,94.8(t,J＝6.1Hz),81.9(dd,J＝21.5Hz,J＝27.5Hz),79.8(dd,J＝4.5Hz,J＝7.8Hz)；
19F NMR(376MHz,CDCl
3)δ-74.0(s,1F),-78.6(s,1F)。
Embodiment 5
The fluoro-1-alkene-3-alkynes of 2-(4 '-iodophenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 94mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-iodophenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-iodophenyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.21(d,J＝8.6Hz,2H),7.50-7.48(m,2H),7.35-7.32(m,5H)；
13C NMR(100MHz,CDCl3)δ159.1(dd,J＝298.7Hz,J＝303.8Hz),137.7,131.6,130.3(dd,J＝1.8Hz,J＝6.4Hz),129.5(dd,J＝3.5Hz,J＝6.0Hz),128.8,128.4,122.5,94.8(t,J＝6.2Hz),93.6,82.0(dd,J＝21.4Hz,27.4Hz),79.8(dd,J＝4.4Hz,J＝7.9Hz)；
19F NMR(376MHz,CDCl
3)δ-73.7(s,1F),-78.4(s,1F)。
Embodiment 6
The fluoro-1-alkene-3-alkynes of 2-(4 '-tolyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 71mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-tolyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-tolyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.51-7.48(m,4H),7.33(t,J＝3.2Hz,3H),7.20(d,J＝8.1Hz,2H),2.37(s,3H)；
13C NMR(100MHz,CDCl
3)δ159.0(dd,J＝297.4Hz,J＝302.6Hz),137.8,131.5,129.3,128.6,128.4,127.7(dd,J＝3.4Hz,J＝5.7Hz),122.9,94.2(t,J＝6.0Hz),80.7(dd,J＝4.6Hz,J＝8.0Hz),21.2；
19F NMR(376MHz,CDCl
3)δ-75.8(s,1F),-80.2(s,1F)。
Embodiment 7
The fluoro-1-alkene-3-alkynes of 2-(2 '-tolyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 71mg (0.2mmol) of 1-trifluoromethyl-2-(2 '-tolyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(2 '-tolyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 60%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.43-7.41(m,2H),7.32-7.27(m,5H),7.25(d,J＝1.6Hz,1H),7.23-7.21(m,1H),2.42(s,3H)；
13C NMR(100MHz,CDCl3)δ158.7(dd,J＝296.4Hz,J＝300.2Hz),137.3(d,J＝1.8Hz),131.5,130.6,130.1-130.0(m,2C),128.7,128.5,128.3,126.1,122.9,83.8(t,J＝6.0Hz),81.0-80.5(m,2C),19.7；
19F NMR(376MHz,CDCl
3)δ-78.9(d,J＝5.7Hz,1F),-80.4(d,J＝5.5Hz,1F)。
Embodiment 8
The fluoro-1-alkene-3-alkynes of 2-(2 '-bromophenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 84mg (0.2mmol) of 1-trifluoromethyl-2-(2 '-bromophenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(2 '-bromophenyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 76%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.64(dd,J＝0.96Hz,1H),7.45-7.43(m,2H),7.42-7.39(m,1H),7.34(td,J＝7.4Hz,J＝1.1Hz,1H),7.30-7.28(m,3H),7.24-7.20(m,1H)；
13C NMR(100MHz,CDCl
3)δ158.9(dd,J＝297.7Hz,J＝300.9Hz),133.3,131.8(t,J＝3.9Hz),131.6(t,J＝2.2Hz),131.5,130.2,128.6,128.3,127.6,124.1(t,J＝2.4Hz),122.7,94.2(t,J＝6.0Hz),81.7(dd,J＝22.8Hz,J＝34.4Hz),80.0(dd,J＝5.8Hz,J＝7.0Hz)；
19F NMR(376MHz,CDCl
3)δ-78.0(s,2F)；
Embodiment 9
The fluoro-1-alkene-3-alkynes of 2-(4 '-p-methoxy-phenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 74mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-p-methoxy-phenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-p-methoxy-phenyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.54-7.49(m,4H),7.33-7.32(m,3H),6.92(d,J＝8.5Hz,2H),3.81(s,3H)；
13C NMR(100MHz,CDCl
3)δ159.2,158.8(dd,J＝296.9Hz,J＝301.8Hz),131.5,129.0(dd,J＝3.2Hz,J＝5.9Hz),128.6,128.4,127.6,122.8,114,94.2(t,J＝6.2Hz),81.9(dd,J＝20.7Hz,J＝28.3Hz),80.8(dd,J＝4.5Hz,J＝8.2Hz),55.3；
19F NMR(376MHz,CDCl
3)δ-79.1(d,J＝11.9Hz,1F),83.0(d,J＝11.9,1F)。
Embodiment 10
The fluoro-1-alkene-3-alkynes of 2-(2 '-naphthyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 98mg (0.2mmol) of 1-trifluoromethyl-2-(2 '-naphthyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(2 '-naphthyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 78%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ8.06(s,1H),7.84-7.79(m,3H),7.71-7.68(m,1H),7.55-7.52(m,2H),7.48-7.46(m,2H),7.34-7.32(m,3H)；
13C NMR(100MHz,CDCl
3)δ159.4(dd,J＝298.1Hz,303.4Hz),133.2,132.8,131.6,128.7,128.5,128.3,128.2,128.1(dd,J＝1.4Hz,J＝6.4Hz),127.7,127.4(t,J＝4.9Hz),126.6,126.5,125.2(dd,J＝2.6Hz,J＝6.2Hz),122.8,94.6(t,J＝6.1Hz),82.7(dd,J＝20.7Hz,J＝27.4Hz),80.6(dd,J＝4.5Hz,J＝8.0Hz)；
19F NMR(376MHz,CDCl3)δ-74.4(d,J＝3.7Hz,1F),-79.2(d,J＝2.3Hz)；
Embodiment 11
The fluoro-1-alkene-3-alkynes of 2-(3 '-nitrophenyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 77mg (0.2mmol) of 1-trifluoromethyl-2-(3 '-nitrophenyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, eluent is the mixed solvent of ethyl acetate and sherwood oil 5:1, about need 20mL, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtain the fluoro-1-alkene-3-alkynes of 2-(3 '-nitrophenyl)-4-phenyl 1,1-bis-by column chromatography purification, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 56%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ8.50(t,J＝1.8Hz,1H),8.18(dd,J＝1.4Hz,1H),7.95-7.93(m,1H),7.60-7.52(m,3H),7.38-7.35(m,3H)；
13C NMR(100MHz,CDCl
3)δ159.6(dd,J＝300.0Hz,J＝305.0Hz),148.5,133.4(dd,J＝3.5Hz,J＝6.5Hz),132.7(dd,J＝2.2Hz,J＝6.7Hz),131.6,129.6,129.1,128.5,122.7(dd,J＝3.7Hz,J＝6.6Hz),122.1,95.7(t,J＝5.9Hz),81.6(dd,J＝22.6Hz,J＝27.0Hz),78.9(dd,J＝4.4Hz,J＝7.4Hz)；
19F NMR(376MHz,CDCl
3)δ-71.9(s,1F),-76.9(s,1F)；
Embodiment 12
The fluoro-1-alkene-3-alkynes of 2-(4 '-trifluoromethyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 82mg (0.2mmol) of 1-trifluoromethyl-2-(4 '-trifluoromethyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(4 '-trifluoromethyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is colorless chromogenic liquid, and productive rate is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.69(dd,J＝8.3,J＝30.0,4H),7.52-7.50(m,2H),7.36-7.35(m,3H)；
13C NMR(100MHz,CDCl
3)δ159.5(dd,J＝299.3Hz,304.8Hz),134.5(dd,J＝9.6Hz,J＝15.6Hz),131.6,130.1(t,34.4Hz),128.9,128.5,128.1(dd,J＝3.4Hz,J＝6.4Hz),125.5(q,J＝3.7Hz),124.0(q,J＝272.3Hz),122.4,95.1(t,6.0Hz),82.1(dd,J＝22.0Hz,J＝27.3Hz),79.5(dd,J＝4.3Hz,J＝7.9Hz)；
9F NMR(376MHz,CDCl
3)δ-62.8(s,3F),-72.6(s,1F),-77.7(s,1F)。
Embodiment 13
The fluoro-1-alkene-3-alkynes of 2-(2 '-thienyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 70mg (0.2mmol) of 1-trifluoromethyl-2-(2 '-thienyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(2 '-thienyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 29%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.53-7.49(m,3H),7.35(t,J＝3.1Hz,4H),7.33-7.31(m,1H)；
13C NMR(100MHz,CDCl
3)δ159.0(dd,J＝297.6Hz,302.6Hz),131.5,131.0(dd,J＝8.5Hz,J＝14.4Hz),128.7,128.4,126.5(dd,J＝2.4Hz,J＝7.1Hz),126.0,123.3(t,J＝6.2Hz),122.6,94.1(t,J＝6.0Hz),79.9(dd,J＝4.3Hz,J＝8.8Hz),78.8(dd,J＝8.1Hz,21.8Hz)；
19F NMR(376MHz,CDCl
3)δ-77.7(s,1F),-78.1(s,1F)。
Embodiment 14
The fluoro-1-alkene-3-alkynes of 2-(1 '-cyclohexyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 70mg (0.2mmol) of 1-trifluoromethyl-2-(1 '-cyclohexyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(1 '-cyclohexyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 78%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.46-7.43(m,2H),7.31-7.30(m,3H),2.30(t,J＝11.0Hz,1H),1.81-1.67(m,5H),1.54-1.45(m,2H),1.37-1.27(m,2H),1.23-1.14(m,1H)；
13C NMR(100MHz,CDCl
3)δ158.1(dd,J＝293.0Hz,J＝296.5Hz),131.4,128.3,128.2,123.2,94.3(t,J＝5.7Hz),84.1(dd,J＝11.6Hz,J＝33.5Hz),80.0(dd,J＝3.9Hz,J＝8.4Hz),35.8,31.4,26.1,25.6；
19FNMR(376MHz,CDCl
3)δ-81.2(d,J＝18.9Hz,1F),-85.3(d,J＝18.8Hz,1F)。
Embodiment 15
The fluoro-1-alkene-3-alkynes of 2-(n-heptyl)-4-phenyl 1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 73mg (0.2mmol) of 1-trifluoromethyl-2-(n-heptyl) ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add phenylacetylene 20mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-(n-heptyl)-4-phenyl 1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 60%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.54-7.42(m,2H),7.31-7.30(m,3H),2.17-2.12(m,2H),1.61-1.54(m,2H),1.33-1.29(m,8H),0.90-0.87(m,3H)；
13C NMR(100MHz,CDCl
3)δ158.6(dd,J＝292.6Hz,J＝295.9Hz),131.4,128.3,128.3,123.1,93.3(t,J＝5.8Hz),81.3(dd,J＝4.0Hz,J＝8.4Hz),78.7(dd,J＝14.4Hz,J＝34.9Hz),31.8,29.0,28.7,27.7,27.1,22.6,14.1；
19F NMR(376MHz,CDCl
3)δ-80.4(d,J＝19.0Hz,1F),-85.7(d,J＝19.0Hz,1F)。
Embodiment 16
2-phenyl-4-(4 '-tolyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 4-methylbenzene acetylene 23mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-tolyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 65%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.61-7.59(m,2H),7.41-7.37(m,4H),7.32-7.28(m,1H),7.14(d,J＝7.9Hz,2H),2.35(s,3H)；
13C NMR(100MHz,CDCl
3)δ159.0(dd,J＝297.6Hz,J＝302.9Hz),138.8,131.5,130.8(dd,J＝1.6Hz,J＝6.3Hz),129.2,128.6,127.9-127.8(m,2C),119.7,94.6(t,J＝6.0Hz),82.5(dd,J＝20.5Hz,J＝27.8Hz),79.8(dd,J＝4.3Hz,J＝8.0Hz),21.5；
19FNMR(376MHz,CDCl
3)δ-75.2(s,1F),-80.0(s,1F)。
Embodiment 17
2-phenyl-4-(4 '-p-methoxy-phenyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then adds 3mL 1,4-dioxane, adds 4-Methoxy-phenylacetylene 26mg (0.2mmol) under stirring.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-p-methoxy-phenyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.61-7.59(m,2H),7.49-7.42(m,2H),7.41-7.37(m,2H),7.32-7.28(m,1H),6.88-6.84(m,2H),3.80(s,3H)；
13C NMR(100MHz,CDCl
3)δ159.9,159.0(dd,J＝297.2Hz,J＝302.7Hz),133.0,130.9(dd,J＝1.6Hz,J＝6.3Hz),128.6,127.9-127.8(m,2C),114,94.3(t,J＝6.1Hz),82.5(dd,J＝20.6Hz,J＝27.8Hz),79.1(dd,J＝4.3Hz,J＝8.0Hz),55.3；
19F NMR(376MHz,CDCl
3)δ-75.5(d,J＝75.5Hz,1F),-80.3(d,J＝4.3Hz,1F)。
Embodiment 18
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-(4 '-N, N-3,5-dimethylphenyl)-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), iodine Asiaization copper 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), 4-N, N-dimethyl benzene acetylene 29mg (0.2mmol), nitrogen substitutes gas, then 3mL Isosorbide-5-Nitrae-dioxane is added.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-N is obtained by column chromatography purification, N-3,5-dimethylphenyl)-1,1-bis-fluoro-1-alkene-3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 74%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.55-7.52(m,2H),7.33-7.26(m,4H),7.22-7.19(m,1H),6.56-6.51(m,2H),2.88(s,6H)；
13C NMR(100MHz,CDCl
3)δ158.8(dd,J＝296.5Hz,J＝302.3Hz),150.3,133.2,132.7,128.5,127.9(dd,J＝3.2Hz,J＝5.9Hz),127.7,111.8,109.5,95.6(t,J＝6.0Hz),82.8(dd,J＝20.7Hz,J＝27.4Hz),78.2(dd,J＝4.2Hz,J＝7.6Hz),40.2；
19F NMR(376MHz,CDCl
3)δ-76.2(d,J＝7.7Hz,1F),-81.3(d,J＝7.6Hz,1F)。
Embodiment 19
2-phenyl-4-(4 '-fluorophenyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 4-fluorobenzene acetylene 24mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-fluorophenyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 77%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.6-7.6(m,2H),7.5-7.5(m,2H),7.4-7.4(m,2H),7.3-7.3(m,1H),7.1-7.0(m,2H)；
13C NMR(100MHz,CDCl
3)δ162.7(d,J＝250.1),159.1(dd,J＝297.9Hz,J＝303.6Hz),133.5(d,J＝8.3Hz),130.6(m,1C),128.6,128.0,127.8(dd,J＝3.2Hz,5.2Hz),118.8(d,J＝3.4Hz),115.7(d,J＝22.1Hz),93.2(t,J＝6.1Hz),82.5-82.2(m,1C),80.2-80.1(m,1C)；
19F NMR(376MHz,CDCl
3)δ-74.9(d,J＝4.1Hz,1F),-79.5(d,J＝4.1Hz,1F),-110.4(s,1F)。
Embodiment 20
2-phenyl-4-(4 '-bromophenyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), 4-bromobenzene acetylene 36mg (0.2mmol), nitrogen substitutes gas, then adds 3mL Isosorbide-5-Nitrae-dioxane.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-bromophenyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 55%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.59-7.57(m,2H),7.48-7.46(m,2H),7.42-7.30(m,5H)；
13CNMR(100MHz,CDCl
3)δ159.1(dd,J＝298.2Hz,J＝303.4Hz),133.6,132.9,131.7,128.6,128.0,127.8(dd,J＝3.2Hz,J＝5.6Hz),122.9,121.7,93.2(t,J＝6.2Hz),82.4(dd,J＝6.7Hz,J＝26.8Hz),81.7(dd,J＝4.5Hz,J＝8.3Hz)；
19F NMR(376MHz,CDCl
3)δ-74.4(s,1F),-78.9(s,1F)。
Embodiment 21
2-phenyl-4-(4 '-trifluoromethyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 4-trifluoromethyl phenylacetylene 34mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-trifluoromethyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 84%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.59-7.58(m,6H),7.43-7.39(m,2H),7.35-7.31(m,1H)；
13CNMR(100MHz,CDCl
3)δ159.3(dd,J＝298.8Hz,J＝304.0Hz),132.8,131.7,130.2(m,1C),128.7,128.1,130.2(dd,J＝3.4Hz,J＝4.9Hz),126.5,125.3(dd,J＝3.7Hz,J＝7.5Hz),123.9(q,J＝272.2Hz),92.9(t,J＝5.6Hz),83.0(dd,J＝4.8Hz,J＝7.9Hz),82.1(dd,J＝20.2Hz,28.2Hz)；
19F NMR(376MHz,CDCl
3)δ-62.9(s,3F),-73.8(s,1F),-78.2(s,1F)。
Embodiment 22
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-(4 '-methyl-formiate base phenyl)-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), 4-ethynyl-benzoate 32mg (0.2mmol), nitrogen substitutes gas, then adds 3mL Isosorbide-5-Nitrae-dioxane.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(4 '-methyl-formiate phenyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 84%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ8.02-7.97(m,2H),7.60-7.53(m,4H),7.42-7.39(m,2H),7.34-7.30(m,1H),3.92(s,3H)；
13C NMR(100MHz,CDCl
3)δ166.4,159.3(dd,J＝298.8Hz,J＝303.9Hz),132.1,131.4,129.8,129.5,129.5,128.7,128.1,127.8(dd,J＝3.5Hz,J＝5.7Hz),93.6(t,J＝6.1Hz),83.5(dd,J＝4.6Hz,J＝8.0Hz),82.3(dd,J＝20.2Hz,J＝28.2Hz),52.2；
19F NMR(376MHz,CDCl
3)δ-72.3(s,1F),-76.8(s,1F)。
Embodiment 23
2-phenyl-4-(6 '-methoxyl group-2 '-naphthyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), 6-methoxyl group-2-naphthalene acetylene 36mg (0.2mmol), nitrogen substitutes gas, then adds 3mL Isosorbide-5-Nitrae-dioxane.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(6 '-methoxyl group-2 '-naphthyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 73%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.94-7.93(m,1H),7.70-7.63(m,4H),7.52-7.46(m,1H),7.43-7.39(m,2H),7.33-7.30(m,1H),7.16-7.13(m,1H),7.09-7.08(m,1H),3.90(s,3H)；
13C NMR(100MHz,CDCl
3)δ159.1(dd,J＝297.7Hz,J＝303.0Hz),158.5,134.3,132.1,131.3,129.4,129.2,128.8,128.6,128.5,127.9(d,J＝1.9Hz),127.8(t,J＝2.9Hz),126.9,119.5,105.9,95.0(t,J＝5.9Hz),82.6(dd,J＝20.5Hz,J＝27.7Hz),80.1(dd,J＝4.4Hz,J＝8.0Hz),55.3；
19F NMR(376MHz,CDCl
3)δ-75.0(s,1F),-79.7(s,1F)。
Embodiment 24
2-phenyl-4-(2 '-pyridyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 2-pyridine acetylene 21mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, the fluoro-1-alkene-3-alkynes of 2-phenyl-4-(2 '-pyridyl)-1,1-bis-and 1,1 is obtained by column chromatography purification, the fluoro-2-phenyl of 1-tri--4-(2 '-pyridyl)-3-propine, its structure is shown below:
This compound is weak yellow liquid, and productive rate is respectively 35% and 25%, and its nuclear magnetic data is as follows:
19F NMR(376MHz,CDCl
3)δ-60.0(s,2F),-73.1(s,1F),-77.4(s,1F)。
19F NMR(376MHz,CDCl
3)δ-60.0(s,3F)。
Embodiment 25
2-phenyl-4-(3 '-thienyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 3-thiophene acetylene 22mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(3 '-thienyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 61%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.60-7.58(m,2H),7.51-7.49(m,1H),7.41-7.37(m,2H),7.32-7.27(m,2H),7.17-7.16(m,1H)；
13C NMR(100MHz,CDCl
3)δ159.1(dd,J＝297.8Hz,J＝303.0Hz),130.7(dd,J＝1.7Hz,J＝6.2Hz),129.8,129.1,128.6,127.9,127.8(dd,J＝3.5Hz,J＝5.8Hz),125.5,121.8,89.5(t,J＝6.0Hz),82.4(dd,J＝20.6Hz,J＝27.9Hz),80.0(dd,J＝4.5Hz,J＝7.9Hz)；
19F NMR(376MHz,CDCl
3)δ-75.5(s,1F),-79.6(s,1F)。
Embodiment 26
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-normal-butyl-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 1-hexin 16mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtain the fluoro-1-alkene-3-alkynes of 2-phenyl-4-normal-butyl-1,1-bis-by column chromatography purification, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 59%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.55-7.53(m,2H),7.36(t,J＝7.6Hz,2H),7.29-7.25(m,1H),2.41(t,J＝7.0Hz,2H),1.59(m,2H),1.47(m,2H),0.94(t,J＝7.3Hz,3H)；
13C NMR(100MHz,CDCl
3)δ159.4(dd,J＝295.6Hz,J＝301.2Hz),128.9,128.4,127.7(dd,J＝3.6Hz,J＝6.0Hz),127.6,95.7(t,J＝6.1Hz),82.2(dd,J＝21.0Hz,J＝26.5Hz),71.5(dd,J＝4.1Hz,J＝8.0Hz),30.7,22.0,19.2,13.6；
19F NMR(376MHz,CDCl
3)δ-77.4(d,J＝9.9Hz,1F),-81.5(d,J＝10.0Hz,1F)。
Embodiment 27
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-cyclopropyl-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 1-cyclopropyl acethlene 13mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtain the fluoro-1-alkene-3-alkynes of 2-phenyl-4-cyclopropyl-1,1-bis-by column chromatography purification, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 59%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.52-7.50(m,2H),7.37-7.33(m,2H),7.29-7.25(m,1H),7.29-7.25(m,2H),1.47-1.41(m,1H),0.89-0.83(m,2H),0.81-0.77(m,2H)；
13C NMR(100MHz,CDCl
3)δ159.4(dd,J＝295.7Hz,J＝301.6Hz),128.7,128.2,127.4(dd,J＝3.6Hz,J＝5.9Hz),127.4,98.4(t,J＝6.0Hz),66.3(dd,J＝4.1Hz,J＝8.0Hz),8.4,0.0；
19F NMR(376MHz,CDCl
3)δ-77.3(d,J＝9.2Hz,1F),-81.1(d,J＝9.2Hz,1F)。
Embodiment 28
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-cyclohexyl-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 1-cyclohexyl-acetylene 22mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtain the fluoro-1-alkene-3-alkynes of 2-phenyl-4-cyclohexyl-1,1-bis-by column chromatography purification, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 61%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.55-7.46(m,2H),7.36(t,J＝7.6Hz,2H),7.29-7.25(m,1H),2.60(s,1H),1.85-1.84(m,2H),1.75-1.72(m,2H),1.55-1.53(m,3H),1.37-1.33(m,3H)；
13C NMR(100MHz,CDCl
3)δ159.2(dd,J＝295.6Hz,J＝301.4Hz),128.9,128.4,127.7(dd,J＝3.4Hz,J＝6.2Hz),127.6,99.7(t,J＝5.9Hz),32.5,29.7,25.9,24.8；
19F NMR(376MHz,CDCl
3)δ-77.2(d,J＝9.8Hz,1F),-81.6(d,J＝10.0Hz,1F)。
Embodiment 29
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-triisopropylsilyl-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add triisopropyl silico acetylene 36mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-triisopropylsilyl-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 88%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.57(d,J＝8.2Hz,2H),7.37(t,J＝7.6Hz,2H),7.28(t,J＝7.4Hz,1H),1.12(s,18H),1.09(s,3H)；
13C NMR(100MHz,CDCl
3)δ160.2(dd,J＝297.3Hz,J＝303.7Hz),130.6(dd,J＝1.5Hz,J＝6.1Hz),128.5,127.7,127.6(dd,J＝3.4Hz,J＝6.2Hz),97.4(dd,J＝4.1Hz,J＝7.2Hz),97.0(dd,J＝4.8Hz,J＝6.5Hz),82.7(dd,J＝21.0Hz,J＝26.4Hz),18.6,11.3；
19F NMR(376MHz,CDCl
3)δ-74.3(s,1F),-78.8(s,1F)。
Embodiment 30
2-phenyl-4-(3 '-hydroxyl-3 '-amyl group)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then adds 3mL Isosorbide-5-Nitrae-dioxane, 3-hydroxyl-3,3-diethyl 1-propine 22mg (0.2mmol) is added under stirring.The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(3 '-hydroxyl-3 '-amyl group)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 72%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.53-7.51(m,2H),7.37(t,J＝7.4Hz,2H),7.31-7.27(m,1H),2.05(br,1H),1.83-1.69(m,4H),1.09(t,J＝7.9Hz,6H)；
13C NMR(100MHz,CDCl
3)δ159.4(dd,J＝297.0Hz,J＝302.4Hz),130.6(dd,J＝1.6Hz,J＝6.4Hz),128.5,127.8,127.6(dd,J＝3.4Hz,J＝6.0Hz),97.1(dd,J＝5.5Hz,J＝6.5Hz),81.7(dd,J＝20.6Hz,J＝27.2Hz),75.7(dd,J＝4.0Hz,J＝8.0Hz),72.8,34.5,8.6；
19F NMR(376MHz,CDCl
3)δ-75.3(d,J＝3.8Hz,1F),-79.6(d,J＝2.7Hz,1F)。
Embodiment 31
2-phenyl-4-(1 '-cyclohexenyl)-1,1-bis-fluoro-1-alkene-3-alkynes
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 2-(1 '-cyclohexenyl)-1-acetylene 21mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, 2-phenyl-4-(1 '-cyclohexenyl)-1 is obtained by column chromatography purification, the fluoro-1-alkene of 1-bis--3-alkynes, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 49%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.56-7.53(m,2H),7.36(t,J＝7.5Hz,2H),7.30-7.26(m,1H),6.22-6.19(m,1H),2.22-2.18(m,2H),2.15-2.12(m,2H),1.70-1.58(4H)；
13C NMR(100MHz,CDCl
3)δ158.8(dd,J＝296.8Hz,J＝302.6Hz),135.6,131.0(dd,J＝1.5Hz,J＝6.5Hz),129.0,128.5,127.7(dd,J＝2.9Hz,J＝5.8Hz),120.4,96.3(t,J＝6.0Hz),82.5(dd,J＝20.6Hz,J＝27.4Hz),77.7(dd,J＝4.5Hz,J＝7.6Hz),29.1,25.7,22.3,21.5；
19F NMR(376MHz,CDCl
3)δ-76.0(d,J＝6.6Hz,1F),-80.8(d,J＝6.4Hz,1F)。
Embodiment 32
The fluoro-1-alkene-3-alkynes of 2-phenyl-4-styroyl-1,1-bis-
The Schlenk pipe getting 10mL loads magneton rubber plug beyond the Great Wall, heat drying, under nitrogen after cooling, add 1 successively, 1, the Tosylhydrazone 68mg (0.2mmol) of 1-trifluoromethyl-2-phenyl ketone, trimethyl carbinol lithium 32mg (0.4mmol), cuprous iodide 8mg (0.04mmol), tetrabutylammonium chloride 11mg (0.04mmol), trifluoromethanesulfonic acid lithium 31mg (0.2mmol), nitrogen substitutes gas, then add 3mL Isosorbide-5-Nitrae-dioxane, under stirring, add 4-phenyl-ethyl acetylene 26mg (0.2mmol).The Electromagnetic Heating agitator of 60 DEG C reacts about 2 hours.After reaction terminates, filter with the silica gel that the core post of 10mL is equipped with 3cm high, appropriate sherwood oil carries out wash-out, gained filtrate utilizes Rotary Evaporators to be removed by reaction solvent, obtain the fluoro-1-alkene-3-alkynes of 2-phenyl-4-styroyl-1,1-bis-by column chromatography purification, its structure is shown below:
This compound is weak yellow liquid, and productive rate is 62%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl
3)δ7.45-7.44(m,2H),7.34-7.21(m,8H),2.90(t,J＝7.3Hz,2H),2.70(t,J＝7.2Hz,2H)；
13C NMR(100MHz,CDCl
3)δ159.4(dd,J＝296.0Hz,J＝301.5Hz),140.5,131.1(dd,J＝1.8 Hz,J＝6.3 Hz),128.6(t,J＝3.2 Hz),128.5,128.4,127.8-127.7(m,2C),126.4,94.7(t,J＝5.9 Hz),82.1(dd,J＝20.7 Hz,J＝27.1 Hz),72.4(dd,J＝4.1 Hz,J＝7.9 Hz),34.9,21.7；
19F NMR(376 MHz,CDCl
3)δ-76.9(d,J＝9.0Hz,1F),-81.0(d,J＝8.7 Hz,1F)。
Claims (10)
1. the synthetic method of bis-fluoro-1,3-yne compounds, comprising:
Tosylhydrazone and the Terminal Acetylenes of α, α, α-trifluorumethylketone react in organic solvent, and under monovalence copper CuX catalysis, and when having alkali and additive to exist, generate fluoro-1, the 3-eneyne derivative of 1,1-bis-, its reaction formula is as follows:
Wherein: R
1represent aromatic base, heterocyclic aromatic base or alkyl; R
2represent aromatic base, heterocyclic aromatic base, thiazolinyl, alkyl or silica-based, described additive comprises tetrabutylammonium chloride or trifluoromethanesulfonic acid lithium.
2. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, is characterized in that, R
1when representing aromatic base, be selected from phenyl, substituted-phenyl or naphthyl, with one or more substituting group on phenyl ring, described substituting group comprises methyl, methoxyl group, nitro, trifluoromethyl or halogen; R
1when representing heterocyclic aromatic base, comprise thienyl, R
1when representing alkyl, described alkyl comprises cyclohexyl or n-heptyl.
3. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, is characterized in that, R
2when representing aromatic base, be selected from phenyl, substituted-phenyl or naphthyl, with one or more identical or different substituting group on phenyl ring, described substituting group comprises methyl, trifluoromethyl, methoxyl group, halogen, ester group or N, N-dimethyl amido, when having multiple substituting group, this multiple substituting group is identical or different, the separate or Cheng Huan of two adjacent substituting groups; R
2when representing heterocyclic aromatic base, comprise thienyl or pyridyl; R
2when representing thiazolinyl, described thiazolinyl comprises cyclohexenyl; R
2when representing alkyl, described alkyl comprises normal-butyl, cyclopropyl, cyclohexyl, styroyl or 1,1-diethyl methylol; R
2when representing silica-based, describedly silica-basedly comprise triisopropylsilyl.
4. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, it is characterized in that, described alkali is selected from salt of wormwood, potassium tert.-butoxide, lithium hydroxide, cesium fluoride or trimethyl carbinol lithium.
5. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, it is characterized in that, described monovalence copper is selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous thiocyanate or four acetonitrile phosphofluoric acids cuprous in one or more, consumption be the 0.1-0.3 of Terminal Acetylenes molar weight doubly.
6. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, is characterized in that, when described additive is tetrabutylammonium chloride, consumption is 0.1 ~ 0.4 times of Terminal Acetylenes molar weight; When described additive is trifluoromethanesulfonic acid lithium, consumption is 1.0 ~ 2.0 times of Terminal Acetylenes molar weight.
7. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, it is characterized in that, described organic solvent is selected from toluene, 1,2-ethylene dichloride, acetonitrile or Isosorbide-5-Nitrae-dioxane.
8. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, it is characterized in that, the Tosylhydrazone of α, α, α-trifluorumethylketone and the mol ratio of Terminal Acetylenes are 1.0:1.0 ~ 2.0:1.0.
9. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, it is characterized in that, temperature of reaction is 40 ~ 110 DEG C, and the reaction times is 1 ~ 4 hour.
10. the synthetic method of 1,1-bis-fluoro-1,3-yne compounds as claimed in claim 1, is characterized in that, also comprise and carry out aftertreatment to reaction product after completion of the reaction.
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| CN113387771A (en) * | 2021-06-16 | 2021-09-14 | 东北师范大学 | Preparation method of chiral fluoroalkyl ternary carbocyclic compound |
| CN113582797A (en) * | 2021-08-17 | 2021-11-02 | 南京林业大学 | Method for synthesizing trifluoromethyl-1, 3-eneyne compound by copper catalysis |
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| CN103570482A (en) * | 2012-08-09 | 2014-02-12 | 北京大学 | Preparation method of 1,3-disubstituted allene compound |
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| CN103570482A (en) * | 2012-08-09 | 2014-02-12 | 北京大学 | Preparation method of 1,3-disubstituted allene compound |
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| 刘振兴等: "过渡金属催化的对甲苯磺酰腙的偶联反应", 《有机化学》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113387771A (en) * | 2021-06-16 | 2021-09-14 | 东北师范大学 | Preparation method of chiral fluoroalkyl ternary carbocyclic compound |
| CN113582797A (en) * | 2021-08-17 | 2021-11-02 | 南京林业大学 | Method for synthesizing trifluoromethyl-1, 3-eneyne compound by copper catalysis |
| CN113582797B (en) * | 2021-08-17 | 2022-08-09 | 南京林业大学 | Method for synthesizing trifluoromethyl-1, 3-eneyne compound by copper catalysis |
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