CN110156668A - 一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 - Google Patents
一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 Download PDFInfo
- Publication number
- CN110156668A CN110156668A CN201910602006.9A CN201910602006A CN110156668A CN 110156668 A CN110156668 A CN 110156668A CN 201910602006 A CN201910602006 A CN 201910602006A CN 110156668 A CN110156668 A CN 110156668A
- Authority
- CN
- China
- Prior art keywords
- cdcl
- nmr
- mhz
- polyfluoroalkyl
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 pyridine compound Chemical class 0.000 title claims abstract description 63
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 34
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 10
- IXRNQIKIVWWFBH-UHFFFAOYSA-N n-(1-phenylethenyl)acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1 IXRNQIKIVWWFBH-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 132
- 239000002904 solvent Substances 0.000 claims description 49
- 238000006243 chemical reaction Methods 0.000 claims description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 24
- 239000012074 organic phase Substances 0.000 claims description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 24
- 238000005406 washing Methods 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 125000006341 heptafluoro n-propyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 239000012299 nitrogen atmosphere Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000010189 synthetic method Methods 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 132
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 46
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 44
- 239000004810 polytetrafluoroethylene Substances 0.000 description 44
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 42
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 24
- 239000012298 atmosphere Substances 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 238000004293 19F NMR spectroscopy Methods 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- 238000000926 separation method Methods 0.000 description 22
- 238000010898 silica gel chromatography Methods 0.000 description 22
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 20
- 238000002390 rotary evaporation Methods 0.000 description 16
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 125000001207 fluorophenyl group Chemical group 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- LHNRYBHXPIJUMP-UHFFFAOYSA-N N-[1-(2-methylphenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1C LHNRYBHXPIJUMP-UHFFFAOYSA-N 0.000 description 2
- FSBBMVZPLLEQRS-UHFFFAOYSA-N N-[1-(4-ethylphenyl)ethenyl]acetamide Chemical compound C(C)C1=CC=C(C=C1)C(=C)NC(C)=O FSBBMVZPLLEQRS-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- SQNJXYSUGKGTPB-UHFFFAOYSA-N n-[1-(4-fluorophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=C(F)C=C1 SQNJXYSUGKGTPB-UHFFFAOYSA-N 0.000 description 2
- WSMPLUKWVPUMKQ-UHFFFAOYSA-N n-[1-(4-methylphenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=C(C)C=C1 WSMPLUKWVPUMKQ-UHFFFAOYSA-N 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- XETRHNFRKCNWAJ-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropanoyl 2,2,3,3,3-pentafluoropropanoate Chemical compound FC(F)(F)C(F)(F)C(=O)OC(=O)C(F)(F)C(F)(F)F XETRHNFRKCNWAJ-UHFFFAOYSA-N 0.000 description 1
- HYLGDGCHYKAAAM-UHFFFAOYSA-N 2,6-diphenyl-4-(trifluoromethyl)pyridine Chemical compound C=1C(C(F)(F)F)=CC(C=2C=CC=CC=2)=NC=1C1=CC=CC=C1 HYLGDGCHYKAAAM-UHFFFAOYSA-N 0.000 description 1
- BREFQHANCGOZHB-UHFFFAOYSA-N 2-(1,1,2,2,3,3,3-heptafluoropropyl)pyridine Chemical compound FC(F)(F)C(F)(F)C(F)(F)C1=CC=CC=N1 BREFQHANCGOZHB-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VPWHLUDHZYLOCA-UHFFFAOYSA-N N-[1-(2-chlorophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1Cl VPWHLUDHZYLOCA-UHFFFAOYSA-N 0.000 description 1
- BKRRFMWOARICES-UHFFFAOYSA-N N-[1-(2-fluorophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1F BKRRFMWOARICES-UHFFFAOYSA-N 0.000 description 1
- MFYDQRWNSCYTIX-UHFFFAOYSA-N N-[1-(3-fluorophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)c1cccc(F)c1 MFYDQRWNSCYTIX-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical class COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- OMRRUNXAWXNVFW-UHFFFAOYSA-N fluoridochlorine Chemical compound ClF OMRRUNXAWXNVFW-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- UFFSXJKVKBQEHC-UHFFFAOYSA-N heptafluorobutyric anhydride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(=O)OC(=O)C(F)(F)C(F)(F)C(F)(F)F UFFSXJKVKBQEHC-UHFFFAOYSA-N 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- CXWLVQOJHMMGTO-UHFFFAOYSA-N n-[1-(3-bromophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC(Br)=C1 CXWLVQOJHMMGTO-UHFFFAOYSA-N 0.000 description 1
- DVUMGIDOTXJYIW-UHFFFAOYSA-N n-[1-(4-chlorophenyl)ethenyl]acetamide Chemical compound CC(=O)NC(=C)C1=CC=C(Cl)C=C1 DVUMGIDOTXJYIW-UHFFFAOYSA-N 0.000 description 1
- WBXRIHAXVFNDKL-UHFFFAOYSA-N n-[1-(4-methoxyphenyl)ethenyl]acetamide Chemical compound COC1=CC=C(C(=C)NC(C)=O)C=C1 WBXRIHAXVFNDKL-UHFFFAOYSA-N 0.000 description 1
- IABIUZOIEZEJIK-UHFFFAOYSA-N n-[1-(4-methylsulfanylphenyl)ethenyl]acetamide Chemical compound CSC1=CC=C(C(=C)NC(C)=O)C=C1 IABIUZOIEZEJIK-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006273 synthetic pesticide Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种合成4‑多氟烷基‑2,6‑二芳基取代吡啶化合物的方法，以N‑（1‑苯基乙烯基）乙酰胺作为底物，多氟烷基羧酸酐作为多氟烷基源，在不添加任何催化剂的条件下，制得4‑多氟烷基‑2,6‑二芳基取代吡啶化合物。该合成方法具有操作简便、原料廉价易得、产物多样化等优点。
Description
技术领域
本发明属于有机氟的化学合成技术领域，具体涉及一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法。
背景技术
吡啶衍生物是一类重要的杂环化合物，广泛存在于天然产物和具有生物活性的分子中，以及应用于合成农药、医药、先进材料等中间体，因此合成吡啶衍生物具有重要的实际应用价值。将含氟基团引入到吡啶分子中，能极大地改变吡啶分子的理化、以及生物性质，增强脂溶性、提高生物利用度等。许多的药物、农药分子含有4-多氟烷基取代吡啶片段。目前文献报道合成该分子片段的方法主要是通过氟-氯交换间接法，或对吡啶底物直接多氟烷基化反应，以及多氟烷基砌块法，但都存在使用昂贵的、不易制备的试剂、反应条件极端、步骤繁琐、适用范围窄、区域选择性低等缺点。本发明提供一种利用廉价易得的多氟烷基羧酸酐与烯酰胺，经串联反应合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法。
发明内容
本发明的目的在于提供一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法，该合成方法具有操作简便、原料廉价易得、产物多样化等优点。
为实现上述目的，本发明采用如下技术方案：
一种4-多氟烷基-2,6-二芳基取代吡啶化合物的合成方法，其是以N-（1-苯基乙烯基）乙酰胺作为底物，多氟烷基羧酸酐作为多氟烷基源，在不添加任何催化剂的条件下，经串联反应，得到4-多氟烷基-2,6-二芳基取代吡啶化合物；其反应式为：
， RF为CF3、CF2H、CF2Cl、C2F5或CF2CF2CF3。
其中，所述N-（1-苯基乙烯基）乙酰胺底物为下述式1-式20中的任意一种：
。
所述4-三氟甲基-2,6-二芳基取代吡啶化合物为下述式1-式24中的任意一种：
。
所述4-二氟甲基-2,6-二芳基取代吡啶化合物为下述式1-式20中的任意一种：
。
所述其他的4-多氟烷基-2,6-二芳基取代吡啶化合物为下述式1-式7中的任意一种：
。
所述4-多氟烷基-2,6-二芳基取代吡啶化合物合成方法的具体步骤如下：在氮气气氛中，N-（1-苯基乙烯基）乙酰胺，多氟烷基羧酸酐混合物置于装有磁力搅拌子的反应器中，加入溶剂，在 60 -100℃ 下反应1-24 h,将反应混合物用乙酸乙酯稀释，用饱和NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，通过硅胶柱纯化，得到所述4-多氟烷基-2,6-二芳基取代吡啶化合物。
所述溶剂为乙腈、1,2-二氯乙烷、或甲苯中的任意一种，优选为1,2-二氯乙烷。
所用N-（1-苯基乙烯基）乙酰胺，多氟烷基羧酸酐、溶剂的摩尔比为(0.2-1):(0.3-1.5):(13-65)。
本发明的有益效果在于：
本发明以简单易得的N-（1-苯基乙烯基）乙酰胺，多氟烷基羧酸酐为原料，在无金属催化下，经串联反应合成4-多氟烷基-2,6-二芳基取代吡啶化合物，官能团的适应性较好，且其操作简便，原料廉价易得、产物多样化等优点。
附图说明
图1为实施例1制得的2,6-二苯基-4-（三氟甲基）吡啶的单晶结构图。
具体实施方式
为了使本发明所述的内容更加便于理解，下面结合具体实施方式对本发明所述的技术方案做进一步的说明，但是本发明不仅限于此。
实施例1
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-苯基乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-二苯基-4-（三氟甲基）吡啶 (分离产率65%)。1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.4 Hz, 4H), 7.93 (s,2H), 7.65 – 7.46 (m, 4H). 19F NMR (376 MHz, CDCl3) δ -64.6 (s, 3F). 13C NMR(101 MHz, CDCl3) δ 158.2 (s), 140.0 (q, J = 33.4 Hz), 138.2 (s), 129.9 (s),128.9 (s), 127.2 (s), 123.3 (q, J = 273.3 Hz), 114.0 (q, J = 3.5 Hz). GC-MSm/z 299 (M+).
实施例2
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（邻甲苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-二邻甲苯基-4-（三氟甲基）吡啶 (分离产率72%)。1H NMR (400 MHz, CDCl3) δ 7.65 (s, 2H), 7.52 (d,J = 6.9 Hz, 2H), 7.43 – 7.31 (m, 6H), 2.49 (s, 6H). 19F NMR (376 MHz, CDCl3) δ-64.5 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 160.9 (s), 139.3 (s), 138.9 (q, J =33.5 Hz), 136.0 (s), 131.0 (s), 129.9 (s), 129.0 (s), 126.1 (s), 123.1 (q, J= 273.4 Hz), 117.6 (q, J = 3.6 Hz), 20.6 (s). GC-MS m/z 327 (M+).
实施例3
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（间甲苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-二间甲苯基-4-（三氟甲基）吡啶 (分离产率71%)。1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 10.3 Hz,4H), 7.89 (s, 2H), 7.46 (t, J = 7.2 Hz, 2H), 7.34 (d, J = 7.3 Hz, 2H), 2.53(s, 6H). 19F NMR (376 MHz, CDCl3) δ -64.6 (s, 3F). 13C NMR (101 MHz, CDCl3) δ158.5 (s), 139.9 (q, J = 33.5 Hz), 138.6 (s), 138.3 (s), 130.6 (s), 128.8(s), 127.8 (s), 124.4 (s), 123.3 (q, J = 273.2 Hz), 114.1 (q, J = 3.6 Hz),21.6 (s). GC-MS m/z 327 (M+).
实施例4
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（对甲苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-二对甲苯基-4-（三氟甲基）吡啶 (分离产率73%)。1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 7.7 Hz,4H), 7.87 (s, 2H), 7.38 (d, J = 7.8 Hz, 4H), 2.49 (s, 6H). 19F NMR (376 MHz,CDCl3) δ -64.6 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 158.1 (s), 139.9 (s), 139.9(q, J = 33.2 Hz), 135.6 (s), 129.6 (s), 127.0 (s), 123.4 (q, J = 273.3 Hz),113.4 (q, J = 3.6 Hz), 21.7 (s). GC-MS m/z 327 (M+).
实施例5
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-乙基苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-乙基苯基）-4-（三氟甲基）吡啶 (分离产率74%)。1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.4Hz, 4H), 7.87 (s, 2H), 7.40 (d, J = 7.4 Hz, 4H), 2.90 – 2.66 (m, 4H), 1.35(t, J = 6.8 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ -64.6 (s, 3F). 13C NMR (101MHz, CDCl3) δ 158.2 (s), 146.3 (s), 139.9 (q, J = 33.2 Hz), 135.9 (s), 128.4(s), 127.1 (s), 123.3 (q, J = 273.2 Hz), 28.8 (s), 15.5 (s). GC-MS m/z 355 (M+).
实施例6
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（2,4-二甲基苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（2,4-二甲基苯基）-4-（三氟甲基）吡啶 (分离产率84%)。1H NMR (400 MHz, CDCl3) δ 7.63 (s,2H), 7.46 (d, J = 7.6 Hz, 2H), 7.18 (d, J = 8.7 Hz, 4H), 2.50 (s, 6H), 2.44(s, 6H). 19F NMR (376 MHz, CDCl3) δ -64.50(s, 3F). 13C NMR (101 MHz, CDCl3) δ160.8 (s), 138.8 (s), 138.7 (q, J = 33.4 Hz), 136.7 (s), 135.9 (s), 131.8(s), 129.9 (s), 126.8 (s), 123.2 (q, J = 273.3 Hz), 117.2 (q, J = 3.6 Hz),21.2 (s), 20.6 (s). GC-MS m/z 355 (M+).
实施例7
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-甲氧基苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-甲氧基苯基）-4-（三氟甲基）吡啶 (分离产率80%)。1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.4Hz, 4H), 7.77 (s, 2H), 7.06 (d, J = 7.4 Hz, 4H), 3.91 (s, 6H). 19F NMR (376MHz, CDCl3) δ -64.7 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 161.1 (s), 157.6 (s),139.8 (q, J = 33.1 Hz), 131.0 (s), 128.5 (s), 123.4 (q, J = 273.3 Hz), 114.2(s), 112.4 (q, J = 3.5 Hz), 55.4 (s). GC-MS m/z 359 (M+).
实施例8
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-甲硫基苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-甲硫基苯基）-4-（三氟甲基）吡啶 (分离产率80%)。1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 6.8Hz, 4H), 7.82 (s, 2H), 7.39 (d, J = 6.8 Hz, 4H), 2.58 (d, J = 1.6 Hz, 6H). 19FNMR (376 MHz, CDCl3) δ -64.7 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 157.5 (s),141.2 (s), 140.0 (q, J = 33.3 Hz), 134.7 (s), 127.4 (s), 126.3 (s), 123.2 (q,J = 273.5 Hz), 113.27 (q, J = 3.6 Hz), 15.39 (s). GC-MS m/z 391 (M+).
实施例9
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（2-氟苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（2-氟苯基）-4-（三氟甲基）吡啶 (分离产率51%)。1H NMR (400 MHz, CDCl3) δ 8.23 (t, J = 7.7 Hz,2H), 8.06 (s, 2H), 7.47 (dd, J = 12.9, 6.6 Hz, 2H), 7.34 (t, J = 7.4 Hz, 2H),7.24 (dd, J = 11.1, 8.6 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -64.6 (s), -116.3– -116.6 (m). 13C NMR (101 MHz, CDCl3) δ 160.8 (d, J = 250.8 Hz), 154.2 (d, J= 2.4 Hz), 139.4 (q, J = 33.5 Hz), 131.3 (d, J = 8.7 Hz), 131.2 (d, J = 2.6Hz), 126.2 (d, J = 10.9 Hz), 124.7 (d, J = 3.5 Hz), 123.1(q, J = 273.5 Hz),118.6 (dq, J = 11.0, 3.5 Hz), 116.4 (d, J = 23.0 Hz). GC-MS m/z 335 (M+).
实施例10
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（3-氟苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（3-氟苯基）-4-（三氟甲基）吡啶 (分离产率50%)。1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.2 Hz,4H), 7.88 (s, 2H), 7.51 (dd, J = 14.1, 7.6 Hz, 2H), 7.26 – 7.13 (m, 2H). 19FNMR (376 MHz, CDCl3) δ -64.70 (s, 3F), -112.16 – -112.27 (m, 1F). 13C NMR (101MHz, CDCl3) δ 163.4 (d, J = 246.1 Hz), 156.9 (d, J = 2.7 Hz), 140.4 (q, J =33.7 Hz), 140.1 (d, J = 7.6 Hz), 130.5 (d, J = 8.1 Hz), 123.0 (q, J = 273.5Hz), 122.6 (d, J = 2.9 Hz), 116.9 (d, J = 21.4 Hz), 114.6 (q, J = 3.6 Hz),114.1 (d, J = 23.1 Hz). GC-MS m/z 335 (M+).
实施例11
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-氟苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于80℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-氟苯基）-4-（三氟甲基）吡啶 (分离产率65%)。1H NMR (400 MHz, CDCl3) δ 8.37 – 7.96 (m, 4H),7.84 (s, 2H), 7.24 (t, J = 7.9 Hz, 4H). 19F NMR (376 MHz, CDCl3) δ -64.7 (s,3F), -111.3 – -111.4 (m, 1F). 13C NMR (101 MHz, CDCl3) δ 164.1 (d, J = 250.1Hz), 157.2 (s), 140.3 (q, J = 33.5 Hz), 134.2 (d, J = 3.1 Hz), 129.0 (d, J =8.5 Hz), 123.1 (q, J = 273.4 Hz), 115.9 (d, J = 21.7 Hz), 113.6 (q, J = 3.5Hz). GC-MS m/z 335 (M+).
实施例12
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（2-氯苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（2-氯苯基）-4-（三氟甲基）吡啶 (分离产率42%)。 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 2H), 7.76 (d,J = 6.1 Hz, 2H), 7.56 (d, J = 6.1 Hz, 2H), 7.43 (d, J = 3.7 Hz, 4H). 19F NMR(376 MHz, CDCl3) δ -64.5 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 157.9 (s), 138.4(q, J =33.6 Hz), 137.9 (s), 132.3 (s), 131.8 (s), 130.3 (s), 130.3 (s), 127.2(s), 122.9 (q, J = 273.5 Hz), 119.1 (q, J = 3.4 Hz). GC-MS m/z 367 (M+).
实施例13
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-氯苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-氯苯基）-4-（三氟甲基）吡啶 (分离产率62%)。 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.0 Hz,4H), 7.84 (s, 2H), 7.50 (d, J = 8.0 Hz, 4H). 19F NMR (376 MHz, CDCl3) δ -64.7(s, 3F). 13C NMR (101 MHz, CDCl3) δ 157.0 (s), 140.3 (q, J = 33.6 Hz), 136.3(s), 136.2 (s), 129.1 (s), 128.3 (s), 123.0 (q, J = 273.5 Hz), 114.0 (q, J =3.5 Hz). GC-MS m/z 367 (M+).
实施例14
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（3-溴苯基）乙烯基）乙酰胺，1.5 mmol 的三氟乙酸酐，最后加入5 mL的溶剂，于60℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（3-溴苯基）-4-（三氟甲基）吡啶 (分离产率55%)。1H NMR (400 MHz, CDCl3) δ 8.29 (s, 2H), 8.07 (d,J = 7.8 Hz, 2H), 7.86 (s, 2H), 7.63 (d, J = 7.9 Hz, 2H), 7.41 (t, J = 7.8 Hz,2H). 19F NMR (376 MHz, CDCl3) δ -64.60 (s, 3F). 13C NMR (101 MHz, CDCl3) δ156.8 (s), 140.4 (q, J = 33.8 Hz), 139.8 (s), 133.0 (s), 130.5 (s), 130.1(s), 125.7 (s), 123.3 (s), 122.9 (q, J = 273.5 Hz), 114.7 (q, J = 3.5 Hz).GC-MS m/z 455 (M+).
实施例15
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-苯基乙烯基）乙酰胺，1.5 mmol 的二氟乙酸酐，最后加入5 mL的溶剂，于100 ℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（二氟甲基）-2,6-二苯基吡啶 (分离产率40%)。1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 7.5 Hz, 4H), 7.82(s, 2H), 7.54 (dt, J = 14.1, 7.6 Hz, 6H), 6.78 (t, J = 55.9 Hz, 1H). 19F NMR(376 MHz, CDCl3) δ -115.3 (d, J = 55.9 Hz, 2F). 13C NMR (101 MHz, CDCl3) δ157.9 (s), 143.9 (t, J = 23.0 Hz), 138.6 (s), 129.6 (s), 128.9(s), 127.1 (s),114.8 (t, J = 5.9 Hz), 113.4 (t, J = 241.0 Hz). GC-MS m/z 281 (M+).
实施例16
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（邻甲苯基）乙烯基）乙酰胺，1.5 mmol 的二氟乙酸酐，最后加入5 mL的溶剂，于100℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（二氟甲基）-2,6-二邻甲苯基吡啶 (分离产率56%)。1H NMR (400 MHz, CDCl3) δ 7.54 (s, 2H), 7.51 (d, J= 7.4 Hz, 2H), 7.41 – 7.30 (m, 6H), 6.78 (t, J = 55.8 Hz, 1H), 2.49 (s, 6H).19F NMR (376 MHz, CDCl3) δ -115.2 (d, J = 55.8 Hz, 2F). 13C NMR (101 MHz,CDCl3) δ 160.6 (s), 142.8 (t, J = 23.1 Hz), 139.8 (s), 135.9 (s), 130.9 (s),129.9 (s), 128.7 (s), 126.0 (s), 118.2 (t, J = 5.8 Hz), 113.3 (t, J = 241.0Hz), 20.6 (s). GC-MS m/z 309 (M+).
实施例17
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（对甲苯基）乙烯基）乙酰胺，1.5 mmol 的二氟乙酸酐，最后加入5 mL的溶剂，于100℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（二氟甲基）-2,6-二对甲苯基吡啶 (分离产率47%)。1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.3 Hz, 4H),7.76 (s, 2H), 7.35 (d, J = 7.3 Hz, 4H), 6.76 (t, J = 56.4 Hz, 1H), 2.47 (s,6H). 19F NMR (376 MHz, CDCl3) δ -115.3 (d, J = 55.9 Hz). 13C NMR (101 MHz,CDCl3) δ 157.7 (s), 143.7 (t, J = 22.9 Hz), 139.7 (s), 135.9 (s, 2F), 129.6(s), 127.1 (s), 114.2 (t, J = 5.9 Hz), 113.5 (t, J = 240.9 Hz), 21.4 (s). GC-MS m/z 309 (M+).
实施例18
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-乙基苯基）乙烯基）乙酰胺，1.5 mmol 的二氟乙酸酐，最后加入5 mL的溶剂，于100 ℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（二氟甲基）-2,6-双（4-乙基苯基）吡啶 (分离产率50%)。1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.6Hz, 4H), 7.77 (s, 2H), 7.39 (d, J = 7.5 Hz, 4H), 6.76 (t, J = 55.9 Hz, 1H),2.78 (q, J = 7.1 Hz, 4H), 1.35 (t, J = 7.3 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ-115.2 (d, J = 56.0 Hz, 2F). 13C NMR (101 MHz, CDCl3) δ 157.8 (s), 146.0 (s),143.7 (t, J = 22.9 Hz), 136.2 (s), 128.4 (s), 127.1 (s), 114.1 (t, J = 5.9Hz), 113.6 (t, J = 240.9 Hz), 28.8 (s), 15.5 (s). GC-MS m/z 337 (M+).
实施例19
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-苯基乙烯基）乙酰胺，1.5 mmol 的氯二氟乙酸酐，最后加入5 mL的溶剂，于60 ℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（氯二氟甲基）-2,6-二苯基吡啶 (分离产率70%). 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.3 Hz, 4H), 7.93(s, 2H), 7.56 (dt, J = 13.4, 7.2 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ -51.9 (s,2F). 13C NMR (101 MHz, CDCl3) δ 158.2 (s), 145.6 (t, J = 27.6 Hz), 138.3 (s),129.8 (s), 128.9 (s), 127.2 (s), 125.4 (t, J = 290.3 Hz), 113.4 (t, J = 4.5Hz). GC-MS m/z 315 (M+).
实施例20
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（2-甲基苯基）乙烯基）乙酰胺，1.5 mmol 的氯二氟乙酸酐，最后加入5 mL的溶剂，于60 ℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以石油醚为洗脱剂，通过硅胶柱层析分离得到4-（氯二氟甲基）-2,6-二邻甲苯基吡啶 (分离产率52%). 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 2H), 7.55 (d, J =7.2 Hz, 2H), 7.46 – 7.32 (m, 6H), 2.52 (s, 6H). 19F NMR (376 MHz, CDCl3) δ -51.7 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 160.9 (s), 144.4 (t, J = 27.7 Hz),139.5 (s), 136.0 (s), 131.0 (s), 129.9 (s), 128.9 (s), 126.1 (s), 125.3 (t, J= 290.2 Hz), 20.6 (s). GC-MS m/z 343 (M+).
实施例21
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（2-甲基苯基）乙烯基）乙酰胺，1.5 mmol 的五氟丙酸酐，最后加入5 mL的溶剂，于120 ℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到4-（五氟乙基）-2,6-二邻甲苯基吡啶 (分离产率22%). 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.53 (d,J = 7.2 Hz, 2H), 7.42 – 7.32 (m, 6H), 2.48 (s, 6H). 19F NMR (376 MHz, CDCl3) δ-84.4 (s, 3F), -116.7 (s, 2F). 13C NMR (101 MHz, CDCl3) δ 160.7 (s), 139.30(s), 137.4 (t, J = 24.6 Hz), 135.9 (s), 131.0 (s), 129.9 (s), 129.0 (s),126.1 (s), 118.9 (qt, J = 286.5, 38.1 Hz), 118.7 (t, J = 5.8 Hz), 112.5 (tq,J = 256.5, 38.4 Hz), 20.51 (s). GC-MS m/z 377 (M+).
实施例22
氮气保护气氛下，在一个置有聚四氟乙烯磁力搅拌子的25 mL反应管中，加入1.0 mmol的N-（1-（4-氟苯基）乙烯基）乙酰胺，1.5 mmol 的七氟丁酸酐，最后加入5 mL的溶剂，于100℃油浴条件下在密闭体系中搅拌反应24 h后冷却至室温，将反应混合物用乙酸乙酯稀释，用饱和 NaHCO3 溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤并通过旋转蒸发除去溶剂，以正戊烷和乙酸乙酯为洗脱剂，通过硅胶柱层析分离得到2,6-双（4-氟苯基）-4-（全氟丙基）吡啶 (分离产率14%). 1H NMR (400 MHz, CDCl3) δ 8.18 (dd, J = 7.3, 5.9Hz, 4H), 7.81 (s, 2H), 7.25 (t, J = 8.3 Hz, 4H). 19F NMR (376 MHz, CDCl3) δ -79.9 (t, J = 9.8 Hz，3F), -111.2 – -111.3 (m, 1F), -113.8 (qd, J = 9.3, 3.2Hz, 2F), -126.2 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 164.11 (d, J = 250.2 Hz),157.08 (s), 138.93 (t, J = 24.7 Hz), 134.18 (d, J = 3.1 Hz), 129.09 (d, J =8.5 Hz), 118.1 (qt, J = 288.6, 34.4 Hz), 116.0 (d, J = 21.7 Hz), 115.4 (tt, J= 255.3, 30.7 Hz), 115.1 (t, J = 6.0 Hz). 108.8 (tq, J = 264.7, 37.8 Hz). GC-MS m/z 435 (M+).
以上所述仅为本发明的较佳实施例，凡依本发明申请专利范围所做的均等变化与修饰，皆应属本发明的涵盖范围。
Claims (8)
1.一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法，其特征在于：N-（1-苯基乙烯基）乙酰胺作为底物，多氟烷基羧酸酐作为多氟烷基源，在不添加任何催化剂的条件下，一步合成4-多氟烷基-2,6-二芳基取代吡啶化合物，结构式为：，其中，RF为CF3、CF2H、CF2Cl、C2F5或CF2CF2CF3。
2.根据权利要求1所述的方法，其特征在于：N-（1-苯基乙烯基）乙酰胺为下述式1-式20中的任意一种：
。
3.根据权利要求1所述的方法，其特征在于：4-三氟甲基-2,6-二芳基取代吡啶化合物为下述式1-式24中的任意一种：
。
4.根据权利要求1所述的方法，其特征在于：4-二氟甲基-2,6-二芳基取代吡啶化合物为下述式1-式20中的任意一种：
。
5.根据权利要求1所述的方法，其特征在于：4-多氟烷基-2,6-二芳基取代吡啶化合物为下述式1-式7中的任意一种：
。
6.根据权利要求1所述的方法，其特征在于：具体合成步骤如下：在氮气气氛中，N-（1-苯基乙烯基）乙酰胺和多氟烷基羧酸酐混合，边磁力搅拌边加入溶剂，60 -100℃反应1-24h，用乙酸乙酯稀释，依次用饱和NaHCO3溶液和饱和食盐水洗涤，有机相用无水 MgSO4 干燥，过滤，旋蒸除去溶剂，纯化，得到4-多氟烷基-2,6-二芳基取代吡啶化合物。
7.根据权利要求6所述的方法，其特征在于：所述溶剂为乙腈、1,2-二氯乙烷、甲苯中的任意一种。
8.根据权利要求6所述的方法，其特征在于：N-（1-苯基乙烯基）乙酰胺，多氟烷基羧酸酐、溶剂的摩尔比为(0.2-1):(0.3-1.5):(13-65)。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910602006.9A CN110156668B (zh) | 2019-07-05 | 2019-07-05 | 一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910602006.9A CN110156668B (zh) | 2019-07-05 | 2019-07-05 | 一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110156668A true CN110156668A (zh) | 2019-08-23 |
| CN110156668B CN110156668B (zh) | 2022-04-26 |
Family
ID=67637678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910602006.9A Expired - Fee Related CN110156668B (zh) | 2019-07-05 | 2019-07-05 | 一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110156668B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115232019A (zh) * | 2022-08-05 | 2022-10-25 | 闽江学院 | 一种3-乙酰氨基三氟甲苯类化合物的合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102276517A (zh) * | 2011-06-29 | 2011-12-14 | 孙光辉 | 二芳基吡啶类药物的合成方法 |
| CN108178745A (zh) * | 2018-03-29 | 2018-06-19 | 河南师范大学 | 含氟烷基吡啶衍生物的合成方法 |
-
2019
- 2019-07-05 CN CN201910602006.9A patent/CN110156668B/zh not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102276517A (zh) * | 2011-06-29 | 2011-12-14 | 孙光辉 | 二芳基吡啶类药物的合成方法 |
| CN108178745A (zh) * | 2018-03-29 | 2018-06-19 | 河南师范大学 | 含氟烷基吡啶衍生物的合成方法 |
Non-Patent Citations (3)
| Title |
|---|
| HUAWEN HUANG等: ""Transition-Metal-Free N-O Reduction of Oximes: A Modular Synthesis of Fluorinated Pyridines"", 《ORGANIC LETTERS》 * |
| JUN-LONG ZHAN等: ""4-HO-TEMPO-Catalyzed Redox Annulation of Cyclopropanols with Oxime Acetates toward Pyridine Derivatives"", 《ACS CATALYSIS》 * |
| KAZUMASA FUNABIKI等: ""Efficient and convenient entry to β-hydroxy-β-trifluoromethyl-β-substituted ketones and 2,6-disubstituted 4-trifluoromethylpyridines based on the reaction of trifluoromethyl ketones with enamines or imines"", 《JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115232019A (zh) * | 2022-08-05 | 2022-10-25 | 闽江学院 | 一种3-乙酰氨基三氟甲苯类化合物的合成方法 |
| CN115232019B (zh) * | 2022-08-05 | 2023-10-27 | 闽江学院 | 一种3-乙酰氨基三氟甲苯类化合物的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110156668B (zh) | 2022-04-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2018103509A1 (zh) | 含连续季碳中心环丙烷氨基磷酸酯类化合物的合成方法 | |
| CN107188832B (zh) | 一种利用二氧化碳合成含三氟甲基的氨基甲酸酯的方法 | |
| CN106957207A (zh) | 2‑芳基（烯基）‑乙烯基磺酰氟化合物的制备方法 | |
| CN1072213C (zh) | 胍衍生物的制备方法及其中间体 | |
| CN106986800B (zh) | 一种β-羰基硫醚的制备方法 | |
| Samanta et al. | Thiol-mediated tandem Michael–aldol reaction: a convenient method for the synthesis of fused cyclopentenones | |
| CN110156668A (zh) | 一种合成4-多氟烷基-2,6-二芳基取代吡啶化合物的方法 | |
| Le Phuong et al. | Environmentally benign and diastereoselective synthesis of 2, 4, 5-trisubstituted-2-imidazolines | |
| Debache et al. | Belokon's Ni (II) complex as a chiral masked glycine for the diastereoselective synthesis of 2-substituted 1-aminocyclopropane carboxylic acids | |
| Diltz et al. | Synthesis of chiral heteroaromatic tetradentate sulfonamide based ligands | |
| CN111233666A (zh) | 一种高效合成三氟甲基化合物的方法、三氟甲基化合物及应用 | |
| CN109897033B (zh) | 一种合成含碘咪唑并[1，2a]吡啶类化合物的方法 | |
| Mahrwald et al. | Ti (OiPr) 4-Mediated nucleophilic substitution of propargylic esters | |
| JP2016198736A (ja) | アミノサリチルアルジミン配位子を金属に配位させた触媒及びこれを用いたヨード環化体の製造方法 | |
| CN108689825B (zh) | 一种合成2-(三氟亚乙基/二氟乙基)-1,3-二酮化合物的方法 | |
| CN110078661B (zh) | 一种3-烯基-2，2′-联吡啶-6-甲酰胺衍生物的制备方法 | |
| CN110028448A (zh) | 一种3-羟基-2,3-二氢异喹啉-1,4-二酮化合物的制备方法 | |
| CN104761420A (zh) | 一种在水相中用甲基芳烃和胺合成酰胺的方法 | |
| CN102127032B (zh) | 一种多取代5-酰基-2-亚胺噻唑啉的合成方法 | |
| Xu et al. | cis-Carbocuperation of acetylenic sulfoxides and corresponding applications in the regio-and stereoselective synthesis of polysubstituted vinyl sulfoxides | |
| CN109096139A (zh) | 一种α-羰基酰胺衍生物的制备方法 | |
| CN108191741A (zh) | 一种用于抗细菌感染药物中间体的合成方法 | |
| CN110156649B (zh) | 一种银催化制备3-苯基-2-苯基二硫烷甲基丙烯酸甲酯类化合物的方法 | |
| CN110669097B (zh) | 一种齐墩果烯衍生物的合成方法 | |
| CN109232249B (zh) | 一种多取代苯甲酸酯的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220426 |