CN108912108A - 三氟甲基化合物及其制备方法及其在农药中的应用 - Google Patents
三氟甲基化合物及其制备方法及其在农药中的应用 Download PDFInfo
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- CN108912108A CN108912108A CN201810680642.9A CN201810680642A CN108912108A CN 108912108 A CN108912108 A CN 108912108A CN 201810680642 A CN201810680642 A CN 201810680642A CN 108912108 A CN108912108 A CN 108912108A
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- compound
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- alkyl
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- -1 Trifluoromethyl compound Chemical class 0.000 title claims abstract description 56
- 239000000575 pesticide Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims description 92
- 239000002585 base Substances 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000003054 catalyst Substances 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 15
- 239000003513 alkali Substances 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 238000009333 weeding Methods 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 238000005286 illumination Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229910052741 iridium Inorganic materials 0.000 claims description 4
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 3
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- DWYMPOCYEZONEA-UHFFFAOYSA-L fluoridophosphate Chemical compound [O-]P([O-])(F)=O DWYMPOCYEZONEA-UHFFFAOYSA-L 0.000 claims 1
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical compound [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 claims 1
- RTRAMYYYHJZWQK-UHFFFAOYSA-N iridium;2-phenylpyridine Chemical compound [Ir].C1=CC=CC=C1C1=CC=CC=N1 RTRAMYYYHJZWQK-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 46
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 abstract description 8
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 168
- 229910052799 carbon Inorganic materials 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- 238000004293 19F NMR spectroscopy Methods 0.000 description 32
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 239000007787 solid Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
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- 150000001721 carbon Chemical group 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 0 *C(*)(*)C1=*(CCN=*C=C)CCO1 Chemical compound *C(*)(*)C1=*(CCN=*C=C)CCO1 0.000 description 7
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- 240000006995 Abutilon theophrasti Species 0.000 description 6
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 240000008067 Cucumis sativus Species 0.000 description 6
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- 241000500437 Plutella xylostella Species 0.000 description 6
- 240000003307 Zinnia violacea Species 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical group C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 5
- QLYGMPXABDCWNV-UHFFFAOYSA-N C(CC)(=O)OC.[F] Chemical compound C(CC)(=O)OC.[F] QLYGMPXABDCWNV-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 241000233679 Peronosporaceae Species 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000005864 Sulphur Substances 0.000 description 5
- 238000011835 investigation Methods 0.000 description 5
- 239000003495 polar organic solvent Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 4
- 240000007124 Brassica oleracea Species 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 238000004134 energy conservation Methods 0.000 description 4
- ZKYQRJXGGLVQML-UHFFFAOYSA-N iridium(3+);2-phenylpyridine Chemical compound [Ir+3].C1=CC=CC=C1C1=CC=CC=N1 ZKYQRJXGGLVQML-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
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- WHELTKFSBJNBMQ-UHFFFAOYSA-L dichlororuthenium;2-pyridin-2-ylpyridine;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ru+2].N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1 WHELTKFSBJNBMQ-UHFFFAOYSA-L 0.000 description 2
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- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Wood Science & Technology (AREA)
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- Environmental Sciences (AREA)
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- Agronomy & Crop Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了三氟甲基化合物及其制备方法及其在农药中的应用。具体地,本发明提供了如式3所示的三氟甲基化合物;在可见光催化下,如式2所示的异氰同如式1所示的三氟甲基叔卤代物反应制备所述三氟甲基化合物的方法;以及所述三氟甲基化合物在农药中的应用。
Description
技术领域
本发明涉及农药领域,具体涉及一种三氟甲基化合物及其制备方法及其在农药中的用途。
背景技术
农药是粮食产量的重要保障,在世界范围内广泛使用。由于含氟化合物的特殊性质,使得其在农药行业中受到重视。通过引入氟原子或含氟基团,可以有效提高化合物的脂溶性、代谢稳定性和生物利用度。含有三氟甲基的化合物是重要的一种,目前已经开发了许多含三氟甲基的农药,包括除草剂和杀菌剂。随着农药的广泛使用,农业害虫和各种真菌的耐药性也在不断增加,已有农药的药效也随之下降,这就要求开发新的农药。
季碳中心的结构普遍存在于自然界中,是许多天然产物和农药的重要结构特征。但是含有三氟甲基季碳中心的农药还未得到充分研究,其中的一个原因是其合成方法发展还不完善。这些方法中最直接的是叔碳中心的三氟甲基化反应,但这类反应要事先合成叔碳化合物,限制了其适用范围。三氟甲基取代烯烃可作为合成子实现三氟甲基季碳中心的构建,但也需要事先合成相应的烯烃底物。由于三氟甲基的吸电子效应,当其邻位有氢原子时,很容易生成一个三氟甲基取代的碳负离子,可以进一步转化为三氟甲基季碳中心,但是在这个过程中很容易发生β-脱氟效应。上述方法中,多数都要用到比较昂贵的三氟甲基试剂或含三氟甲基的底物,反应的成本较高。以上因素限制了含三氟甲基季碳中心的化合物在农药中的应用。因此,开发便捷合成含三氟甲基季碳中心化合物的方法具有重要意义。
近年来,可见光促进的反应得到了长足发展,因为其反应条件温和,易于操作而受到重视。三氟甲基取代的叔卤代物可以在可见光促进下通过单电子转移过程产生自由基,进而和不饱和底物反应,构建含三氟甲基的季碳中心(Huan,F.;Chen,Q.-Y.;Guo,Y.J.Org.Chem.2016,81,7051.)。异氰酸酯类化合物可以参与自由基反应,常见的是2-异氰基-1,1’-联苯通过自由基反应构建6-取代的氮杂菲化合物(Zhang,B.;Studer,A.Chem.Soc.Rev.2015,44,3505.)。但本领域中尚无以此方法合成含三氟甲基的农药的研究。
综上所述,本领域迫切需要开发便捷一种含有三氟甲基季碳中心化合物,及合成含三氟甲基季碳中心化合物的方法,以及所述化合三氟甲基季碳中心化合物在农药中的应用。
发明内容
本发明的目的就是提供一种含有三氟甲基季碳中心化合物,及合成含三氟甲基季碳中心化合物的方法,以及所述化合三氟甲基季碳中心化合物在农药中的应用。
在本发明的第一方面,提供了一种如式3所示的化合物或其对映异构体或非对映异构体或其混合物,或其盐:
其中,
R6为C1-C4烷基;
环Ar1为苯环,且所述苯环被一个或多个R4基团取代,R4独立地选自下组:H、卤素、-NO2、取代或未取代的C1-C6烷基、取代或未取代的C1-C4烷氧基、取代或未取代的C1-C4烷硫基、取代或未取代的C1-C5酰基、取代或未取代的C1-C5酯基;
环Ar2如式2.2所示:
其中,各个R5独立地选自下组:H、卤素、取代或未取代的C1-C6烷基、取代或未取代的C3-C12环烷基、取代或未取代的C1-C4烷氧基、取代或未取代的C1-C4烷硫基、取代或未取代的C6-C20芳基、取代或未取代的C3-C20杂芳基、取代或未取代的C1-C4烷基磺酰基、取代或未取代的C1-C5酯基、取代或未取代的C1-C5酰基;且n=1、2、3或4;
环A选自下组:无、取代或未取代的5到12元碳环、或取代或未取代的5到12元杂环;所述杂环为环上一个或多个碳原子被杂原子替换,且所述杂原子各自独立地选自:O、N或S;
各个R3独立地选自下组:H、取代或未取代的C1-C6烷基、取代或未取代的C6-C20芳基、取代或未取代的C6-C12芳基-C1-C4烷基;且z=1、2、3或4;
所述的取代是指基团上的氢被选自下组的取代基取代:卤素、C1-C3烷基、羟基、氨基、-NO2。
在另一优选例中,各个R4独立地选自下组:H、卤素(优选地,所述卤素为Br、Cl或F;更优选地,所述卤素为F或Cl)、-NO2、C1-C6烷基(优选地,为C1-C4烷基)。
在另一优选例中,各个R4独立地选自下组:H、卤素(优选地,所述卤素为Br、Cl或F;更优选地,所述卤素为F或Cl)、C1-C6烷基(优选地,为C1-C4烷基)。
在另一优选例中,各个R4为实施例中对应的各基团。
在另一优选例中,环Ar1被1个或2个R4基团取代。
在另一优选例中,环A为单环或多环。
在另一优选例中,各个R5独立地选自下组:H、卤素(优选地,所述卤素为Br、Cl或F;更优选地,为Cl或F;最优选地,为F)、C1-C4烷基、C1-C4卤代烷基(优选地,所述C1-C4卤代烷基为C1-C4氟代烷基;更优选地,为-CF3)、C1-C4烷氧基、C1-C4烷硫基、C1-C4烷基磺酰基、C1-C5酯基、C6-C14芳基(优选地,所述C6-C14芳基,为苯基)。
在另一优选例中,各个R5独立地为实施例中对应的各基团。
在另一优选例中,n=1、2或3;优选地,n=1或2。
在另一优选例中,R6为甲基。
在另一优选例中,各个R3独立地选自下组:H、C1-C6烷基、C6-C12芳基、C6-C12芳基-C1-C4烷基。
在另一优选例中,各个R3独立地选自下组:H、C1-C4烷基、苯基、苯基-C1-C4烷基。
在另一优选例中,各个R3为实施例中对应的各基团。
在另一优选例中,z=1、2或3;优选地,z=1或2。
在另一优选例中,环Ar2具有如式2.2.1所示结构,或具有如式2.2.2所示结构:
(i)
R5及n的定义如前所述;
或
(ii)
其中,环B为5到7元杂环,或5到7元碳环。
在另一优选例中,式2.2.2化合物中,环B上碳原子被1或2个杂原子取代。
在另一优选例中,所述杂原子为O或S。
在另一优选例中,所述化合物具有式3.1所示结构
其中,R1及R2独立地选自下组:H、取代或未取代的C1-C6烷基、取代或未取代的C6-C20芳基、取代或未取代的C6-C12芳基-C1-C4烷基。
在另一优选例中,R1及R2独立地选自下组:H、C1-C4烷基、C6-C12芳基、C6-C12芳基-C1-C4烷基。
在另一优选例中,R1及R2独立地选自下组:H、C1-C4烷基、苯基、苯基-C1-C4烷基。
在另一优选例中,R1及R2独立地为实施例中对应的各基团。
在另一优选例中,式3化合物选自下表所示化合物:
本发明的第二方面提供了一种制备如第一方面所述化合物或其对映异构体或非对映异构体或其混合物,或其盐的方法,所述方法为在有机溶剂中,在催化剂和碱存在时,在可见光照射下,将式1化合物及式2化合物进行反应,从而形成式3化合物:
其中,环Ar1、环Ar2、R3、R6及z的定义如前所述;
X为F、Cl、Br或I。
在另一优选例中,式1中X为Cl或Br;优选地,X为Br。
在另一优选例中,所述式2化合物选自下表中所示化合物:
在另一优选例中,所述式1化合物为如式1.1所示化合物:
其中,R1、R2、R6、X的定义如前所述。
在另一优选例中,式1.1中,X为Br。
在另一优选例中,所述式1化合物选自下表中所示化合物:
在另一优选例中,所述方法包括步骤:
(1)提供一种反应体系,
所述反应体系包括式1化合物、式2化合物、催化剂、碱及有机溶剂;
(2)所述反应体系在可见光照射下进行反应,得到式3化合物。
在另一优选例中,式1化合物:式2化合物:可见光催化剂:所述碱的摩尔比为1.2:(0.5~2):(0.01~0.10):(1~5);优选地,为1.2:(0.8~1.2):(0.01~0.05):(2~4);更优选地,为1.2:1:0.02:3。
在另一优选例中,所述有机溶剂与式2化合物的用量比(ml:mmol)为(5~20):1;优选地,为10:1。
在另一优选例中,所述碱为有机碱、无机碱、或其组合。
在另一优选例中,所述碱选自下组:甲醇钠、叔丁醇钾、碳酸钠、碳酸钾、或其组合。
在另一优选例中,所述催化剂为铱的配合物和/或钌的配合物。
在另一优选例中,所述催化剂选自下组:三联吡啶氯化钌六水合物(Ru(bpy)3Cl2·6H2O)、三(2-苯基吡啶)铱(III)(Ir(ppy)3)、二(2-苯基吡啶)(4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐(Ir(ppy)2(dtbbpy)PF6)、二[2-(2,4-二氟苯基)-5-(三氟甲基)吡啶](4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐([Ir{dF(CF3)ppy}2(dtbbpy)]PF6)、或其组合。
在另一优选例中,所述有机溶剂为极性有机溶剂、非极性有机溶剂、或其组合;优选地,所述有机溶剂为极性有机溶剂。
在另一优选例中,所述有机溶剂选自下组:N,N-二甲基甲酰胺(DMF)、N-甲基吡咯烷酮(NMP)、甲苯、二氯甲烷(DCM)、乙腈、或其组合。
在另一优选例中,步骤(2)中,所述反应的反应温度为0~80℃;优选地,为10~50℃;更优选地,为15~30℃。
在另一优选例中,步骤(2)中,所述反应的反应时间为4~20h;优选地为8~16h;更优选地,为10~14h。
在另一优选例中,所述可见光由8~16w节能灯提供。
在另一优选例中,步骤(2)中,所述反应在惰性氛围中进行;优选地,在氮气氛围中进行。
在另一优选例中,步骤(2)还包括后在反应完后进行处理步骤。
在另一优选例中,所述后处理步骤包括萃取剂萃取、过滤、水洗、干燥、浓缩/柱层析分离纯化处理,得到经后处理的式3化合物。
本发明的第三方面提供了一种农药组合物,所述农药组合物包含如第一方面所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐。
本发明的第四方面提供了如第一方面所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐或如第三方面所述农药组合物的用途,用于杀菌、杀虫或除草。
在另一优选例中,所述杀菌是指防治黄瓜霜霉病、小麦白粉病、玉米锈病和/或黄瓜炭疽病;优选地,是指防治黄瓜霜霉病。
在另一优选例中,所述杀虫是指防治小菜蛾、粘虫、桃蚜和/或朱砂叶螨;优选地,是指防治小菜蛾和/或桃蚜。
在另一优选例中,所述除草是指防治百日草、苘麻、金狗尾和/或稗草;优选地,是指防治百日草和/或苘麻。
本发明的第五方面提供了一种杀菌、杀虫或除草的方法,包括步骤:给需要的植物或土壤环境施用如第一方面所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐,或如第三方面所述农药组合物。
应理解,在本发明范围内中,本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合,从而构成新的或优选的技术方案。限于篇幅,在此不再一一累述。
具体实施方式
发明人经过广泛而深入的研究,优化了在可见光促条件下,异氰酸酯类化合物与三氟甲基取代的叔卤代物的反应条件。在碱存在下,异氰酸酯类化合物与三氟甲基取代的叔卤代物反应生成三氟甲基季碳中心化合物。该反应收率高。并以此方法合成了一系列具有农药活性的三氟甲基季碳中心化合物。基于此完成了本发明。
定义
术语“C1-C6烷基”是指一价饱和脂族烃基,具有1至6个碳原子,包括直链和支链烃基,如甲基(即CH3-)、乙基(即CH3CH2-)、正丙基(即CH3CH2CH2-)、异丙基(即(CH3)2CH-)、正丁基(即CH3CH2CH2CH2-)、异丁基(即(CH3)2CHCH2-)、仲丁基(即(CH3)(CH3CH2)CH-)、叔丁基(即(CH3)3C-)、正戊基(即CH3CH2CH2CH2CH2-)、新戊基(即(CH3)3CCH2-)。
术语“C1-C4烷基”是指一价饱和脂族烃基,具有1至4个碳原子,包括直链和支链烃基,如甲基(即CH3-)、乙基(即CH3CH2-)、正丙基(即CH3CH2CH2-)、异丙基(即(CH3)2CH-)、正丁基(即CH3CH2CH2CH2-)、异丁基(即(CH3)2CHCH2-)、仲丁基(即(CH3)(CH3CH2)CH-)。
如本文所用,术语“取代或未取代的”指所述基团可以是未取代的,或者所述基团中的H被一个或多个(较佳地1-6个,更佳地1-3个)取代基所取代。
如本文所用,所述的“取代”或“取代的”指所述基团具有一个或多个(较佳地1-6个,更佳地1-3个)选自下组的取代基:卤素、羟基、-NH2、硝基、-CN、C1-C4烷基、C1-C4卤代烷基、C1-C4烷氧基、C3-C6环烷基、C2-C4链烯基、C2-C4炔基、苯基、苄基。
如本文所用,术语“C3-C12环烷基”指具有具有单环或多环(包括稠合体系,桥环体系和螺环体系)的环状烷基。在稠环体系中,一个或多个环可以是环烷基、杂环的、芳基或杂芳基,只要连接位点是通过环烷基的环。合适的环烷基的例子包括:例如,金刚烷基、环丙基、环丁基、环戊基和环辛基。
如本文所用,术语“烷氧基”指-O-烷基,其中所述烷基可以是饱和或不饱和的、可以是支链、直链的、或环状的。优选地,烷氧基具有1-4个碳原子,即C1-C4烷氧基。代表性的例子包括(但并不限于):甲氧基、乙氧基、丙氧基。
如本文所用,术语“烷硫基”指-S-烷基,其中所述烷基可以是饱和或不饱和的、可以是支链、直链的、或环状的。优选地,烷硫基具有1-4个碳原子,即C1-C4烷硫基。代表性的例子包括(但并不限于):甲硫基、乙硫基、丙硫基。
如本文所用,术语“C6-C20芳基”是指6至20个(较佳6-14个)碳原子的单价芳香族碳环基团,它具有单环(如苯基)或稠环(如萘基或蒽基),如果连接点在芳香碳原上,稠环可能是非芳香性的(如2-苯并噁唑酮,2H-1,4-苯并噁嗪-3(4H)-酮-7-基等)。优选的芳基包括苯基和萘基。该术语包括取代或未取代的形式,其中取代基的定义如上。
如本文所用,术语“卤代”或“卤素”是指氟、氯、溴和碘。
如本文所用,术语“杂芳基”是指环内具有1至10个碳原子和1至4个选自氧、氮和硫的杂原子的芳香基团。至于,指明碳原子的数目的术语,例如“C3-C20杂芳基”表示具有3-20个碳原子和1至4个选自氧、氮和硫的杂原子的芳香基团的杂芳基。其它类似。这样的杂芳基可以是单环的(如吡啶基或呋喃基)或稠环(如吲嗪基(indolizinyl)或苯并噻吩基),其中,所述稠环可以是非芳香性的和/或含有一个杂原子,只要连接点是通过芳香性杂芳基的原子。在一实施例中,杂芳基的环原子氮和/或硫任选地被氧化为N-氧化物(N-O),亚磺酰基或磺酰基。优选地杂芳基包括吡啶基、吡咯基、吲哚基、噻吩基和呋喃基。该术语包括取代或未取代的杂芳基。
如本文所用,术语“碳环”或“碳环的”是指饱和的、部分饱和的或不饱和的基团,可以是芳香性的也可以是非芳香性的,具有单环或稠环(包括桥环体系和螺环体系,环内具有5至12个碳原子,在稠环体系中,一个或多个环可以是环烷基、或芳基。
如本文所用,术语“杂环”或“杂环的”或“杂环烷基”或“杂环基”是指饱和的、部分饱和的或不饱和的基团,具有单环或稠环(包括桥环体系和螺环体系,环内具有1至10个碳原子和1至4个(如2个)选自氮、硫或氧的杂原子,在稠环体系中,一个或多个环可以是环烷基、芳基或杂芳基。
如本文所用,术语“取代的杂环的”或“取代的杂环烷基”或“取代的杂环基”是指被1到5(如1至3)个取代基所取代的杂环基团,所述取代基与取代的环烷基所定义的取代基相同。
如本文所用,术语“C1-C5酯基”是指-COO-(C1-C4烷基)。
如本文所用,术语“C1-C5酰基”是指-C(O)-(C1-C4烷基)。
合成方法
三氟甲基叔溴代物和2-异氰基-1,1’-联苯这类化合物可以在可见光催化剂的存在下,经由可见光照射可以引发单电子转移反应,产生的自由基和异氰反应、关环、芳构化,得到含有三氟甲基季碳中心的化合物。
本发明的目的是提供一种利用三氟甲基叔卤代物在可见光照射下,和2-异氰基-1,1’-联苯类化合物发生反应,构建含三氟甲基季碳中心的化合物。具体地说是一种在室温~80℃下、在极性有机溶剂或无极性有机溶剂中、在催化剂(例如可见光催化剂)和碱存在下,通过可见光的照射实现三氟甲基叔卤代物和2-异氰基-1,1’-联苯类化合物的反应构建含三氟甲基季碳中心化合物的方法,通过所述方法反应1-12小时可得到目标产物。
其中,所述的三氟甲基叔卤代物(式1化合物)、2-异氰基-1,1’-联苯类化合物(式2化合物)、可见光催化剂、碱的摩尔比为1.2:1:0.02:3。所述的可见光催化剂为铱或钌的配合物,如三联吡啶氯化钌六水合物(Ru(bpy)3Cl2·6H2O)、三(2-苯基吡啶)铱(III)(Ir(ppy)3)、二(2-苯基吡啶)(4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐(Ir(ppy)2(dtbbpy)PF6)、二[2-(2,4-二氟苯基)-5-(三氟甲基)吡啶](4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐([Ir{dF(CF3)ppy}2(dtbbpy)]PF6)。
所述的极性有机溶剂可以是N,N-二甲基甲酰胺(DMF)、N-甲基吡咯烷酮(NMP)、甲苯、二氯甲烷、或乙腈。
所述的碱是有机碱(如甲醇钠、叔丁醇钾),或无机碱(如一价金属盐,如、碳酸钠、碳酸钾等)。
所采用的可见光源为12W节能灯。
采用本发明的方法,建议在氮气中进行。
上述的反应产物经过用有机溶剂萃取,过滤,经水洗,干燥,浓缩,柱层析分离纯化处理。
本发明的主要优点包括:
(a)本发明提供的化合物表现出良好的农药活性;特别是具有良好的杀菌活性。
(b)本发明的制备方法采用可见光催化,反应条件温和。
(c)本发明的制备方法对异氰及三氟甲基叔溴代物的普适性好。
(d)本发明的制备方法收率高。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件,或按照制造厂商所建议的条件。除非另外说明,否则百分比和份数是重量百分比和重量份数。
实施例1反应条件优化
反应先在DMF中进行,以Ir(ppy)3作为光催化剂,没有碱(Base)存在下反应12小时(表1,序号1),19F NMR检测发现没有新的氟峰产生;当在反应体系中加入二当量的磷酸钾,反应12小时后,19F NMR检测也几乎没有新的峰;当用碳酸钾作为碱,发现在-61.7ppm处有一个新峰,氟谱产率(Yield)为33%,经分离鉴定为3a。随后对不同的碱进行了考察,结果发现效果最好的是无机碱碳酸钠,有机碱如甲醇钠、叔丁醇钾效果较差(表1,序号2-6)。对反应溶剂(Solvent)的考察发现,反应在二氯甲烷(DCM)中进行时,可以得到92%的氟谱收率(表1,序号9)。
随后对不同的可见光催化剂(Catalyst)进行考察(表1,序号9,11-13),采用不同的铱和钌的配合物,均可得到产物,效果最好的催化剂是三(2-苯基吡啶)铱(III)(表1,序号9)。
对碱的用量的考察表明,当把碳酸钠的用量增加为3当量(equiv)(0.6mmol)反应的收率有所提高,能够达到96%的氟谱收率(表1,序号14)。继续增加碳酸钠的用量至5当量(表1,序号15),反应收率几乎不再受影响。随后进行了控制实验,将反应体系至于黑暗中搅拌12小时(表1,序号16),19F NMR检测发现没有新的氟峰产生,表明没有产物生成,这一结果说明了可见光对于这一反应过程是必要的。
表1反应条件优化a
a反应条件:1a:0.24mmol;2a:0.2mmol;催化剂:0.004mmol;碱用量0.4-1mmol;溶剂:2mL;在N2气气氛中,采用12W节能灯照射,室温(rt)下反应12小时。b采用19F NMR测定获得产率。c将反应体系置于黑暗中,室温下搅拌12小时。
表中,催化剂为可见光催化剂、可见光为12W节能灯、DMF为N,N-二甲基甲酰胺、NMP为N-甲基吡咯烷酮、DCM为二氯甲烷、rt为室温。
实施例2底物(异氰)普适性
得到了最优化的反应条件后,对三氟甲基叔溴代物与异氰可见光促进的反应的底物(异氰)普适性进行了研究。实验结果如表2所示,反应对底物的普适性较好。在最优化的条件下,含有各种取代基的异氰都能发生反应,以良好的产率得到含三氟甲基季碳中心的化合物。表2异氰的普适性考察a
a反应条件:1a:0.6mmol;2:0.5mmol;Ir(ppy)3:0.01mmol;Na2CO3:1.5mmol;DCM:5mL;在N2气气氛中,采用12W节能灯照射,室温(rt)下反应12小时。b分离产率(yield)。Ar1和Ar2为带有取代基的芳环,可见光为12W节能灯,DCM为二氯甲烷。
实施例3三氟甲基叔溴代物普适性
随后我们对三氟甲基叔溴代物的普适性进行了考察。在最优化的条件下,含有各种取代基的叔溴代物都可以参与反应,与异氰2a在可见光条件下能以良好的产率得到含三氟甲基季碳中心的化合物。
表3叔溴代物的普适性考察a
a反应条件:1:0.6mmol;2a:0.5mmol;Ir(ppy)3:0.01mmol;Na2CO3:1.5mmol;DCM:5mL;在N2气气氛中,采用12W节能灯照射,室温(rt)下反应12小时。R1和R2为氢、烷基或芳基,可见光为12W节能灯,DCM为二氯甲烷。
实施例4化合物合成
可见光促进的三氟甲基取代叔溴代物和异氰反应的一般操作:
干燥的10mL反应管抽换氮气三次,在氮气保护下,向反应管中加入磁子,异腈0.5mmol,三氟甲基取代叔溴代物0.6mmol,三(2-苯基吡啶)铱(III)0.01mmol(6.55mg),碳酸钠:1.5mmol(159.0mg),二氯甲烷5mL。将反应管置于24W节能灯照射下,室温搅拌12小时。反应结束后,加入水和乙酸乙酯,分液,水层用乙酸乙酯萃取,合并有机相,用无水硫酸钠干燥。有机层经真空浓缩,柱层析纯化。
1)3aa(2-(6-菲啶基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯)
157.2mg,收率81%,白色固体.熔点:136-138℃.1H NMR(400MHz,CDCl3):δ8.69(d,J=8.3Hz,1H),8.57(dd,J=7.6,2.1Hz,1H),8.12-8.08(m,2H),7.83(t,J=7.7Hz,1H),7.75-7.70(m,2H),7.65(t,J=7.7Hz,1H),4.47-4.35(m,2H),4.09(t,J=9.1Hz,1H).13CNMR(100MHz,CDCl3):δ165.0,161.3,151.2,142.1,133.9,130.8,130.4,128.8,128.3,126.9,126.5(q,J=3.7Hz),124.5,124.2,123.4(q,J=283.7Hz),122.6,121.8,68.4,68.0(q,J=26.3Hz),54.8,53.7.19F NMR(376MHz,CDCl3):δ-61.7(s,3F).IR(KBr):2949,2924,2879,2851,1760,1655,1615,1576,1526,1488,1460,1445,1435,1351,1318,1266,1203,1186,1167,1071,1045,1035,1012,972,934,907,890,870,838,797,758,725,716,696,657,633,614,584,555,536cm-1.MS(EI,m/z,%):388(M+,1.93),149(100),84(25.22).HRMS(EI)计算值calcd.for C20H15N2O3F3:388.1035;实测值found:388.1036.
2)3ab 2-(8-叔丁基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
175.4mg,收率79%,白色固体.熔点:158-160℃.1H NMR(400MHz,CDCl3):δ8.61(d,J=8.8Hz,1H),8.56-8.52(m,1H),8.14(s,1H),8.11-8.08(m,1H),7.92(d,J=8.7Hz,1H),7.73-7.66(m,2H),4.48-4.32(m,2H),4.11(t,J=9.4Hz,2H).13C NMR(100MHz,CDCl3):δ165.0,161.5,151.4,149.8,142.0,131.7,130.8,128.7,128.3,128.2,124.3,124.2,123.5(q,J=283.6Hz),122.8(q,J=3.9Hz),122.3,121.6,68.3,68.1(q,J=26.2Hz),54.9,53.6,35.1,31.2.19F NMR(376MHz,CDCl3):δ-61.7(s,3F).IR(KBr):3075,2967,2951,2906,1765,1664,1577,1568,1526,1478,1460,1436,1396,1350,1312,1292,1262,1189,1171,1093,1072,1042,1008,942,919,877,867,826,796,742,728,701,678,657,646,587,579,569,537cm-1.HRMS(ESI)计算值calcd.for C24H24O3N2F3(M+H+):445.1734;实测值found:445.1725.
3)化合物3ac 2-(8-甲氧基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
1565.2mg,收率79%,白色固体.熔点:121-124℃.1H NMR(400MHz,CDCl3):δ8.58(d,J=8.3Hz,1H),8.50-8.45(m,1H),8.10-8.04(m,1H),7.72-7.63(m,2H),7.50-7.45(m,2H),4.49-4.35(m,2H),4.09(t,J=9.6Hz,2H),3.96(s,3H),3.89(s,3H).13C NMR(100MHz,CDCl3):δ165.0,161.5,158.2,150.3,141.4,130.8,128.39,128.35,127.8,125.8,124.3,124.2,123.6(q,J=283.7Hz),121.5,121.3,106.6(q,J=4.0Hz),68.4,68.1(q,J=26.3Hz),55.4,54.8,53.7.19F NMR(376MHz,CDCl3):δ-61.4(s,3F).IR(KBr):2950,2914,2838,2257,2236,1756,1660,1621,1573,1531,1484,1462,1446,1430,1417,1364,1315,1249,1227,1190,1163,1138,1116,1098,1063,1036,1007,981,946,918,884,860,834,817,796,771,742,724,699,666,643,589,568,554,535cm-1.HRMS(ESI)for C21H18O4N2F3(M+H+):计算值Calcd:419.1213;实测值Found:419.1209.
4)化合物3ad 2-(8-甲硫基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
193.2mg,收率89%,黄色固体.熔点:135-138℃.1H NMR(400MHz,CDCl3):δ8.54(d,J=8.8Hz,1H),8.49(dd,J=6.5,3.3Hz,1H),8.11-8.05(m,1H),7.85(s,1H),7.72-7.67(m,3H),4.49-4.35(m,2H),4.09(t,J=9.6Hz,2H),3.96(s,3H),2.55(s,3H).13C NMR(100MHz,CDCl3):δ164.9,161.4,150.2,141.8,138.5,131.2,130.8,129.4,128.5,128.4,125.0,124.1,123.4(q,J=283.7Hz),122.8,121.7(q,J=4.0Hz),121.5,68.4,68.0(q,J=26.2Hz),54.8,53.7,15.3.19F NMR(376MHz,CDCl3):δ-61.5(s,3F).IR(KBr):2956,2923,1763,1657,1606,1565,1522,1474,1460,1434,1406,1354,1320,1306,1265,1207,1186,1169,1117,1101,1067,1039,1016,974,940,925,908,888,855,824,796,786,759,740,723,693,667,640,585,565,551,536cm-1.HRMS(ESI)计算值calcd.for C21H18O3N2F3S(M+H+):435.0985;实测值found:435.0981.
5)化合物3ae 2-(8-苯基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
194.9mg,收率84%,白色固体.熔点:135-138℃.1H NMR(400MHz,CDCl3):δ8.73(d,J=8.6Hz,1H),8.59-8.55(m,1H),8.38(s,1H),8.11(t,J=7.6Hz,2H),7.77-7.66(m,4H),7.51(t,J=7.5Hz,2H),7.42(t,J=7.3Hz,1H),4.46-4.29(m,2H),4.12-4.00(m,2H),3.97(s,3H).13C NMR(100MHz,CDCl3):δ165.0,161.4,151.3,142.1,139.9,139.4,132.9,130.9,129.5,129.2,128.8,128.4,128.0,127.0,125.0,124.6(q,J=3.5Hz),124.1,123.5(q,J=283.7Hz),123.2,121.8,68.4,68.1(q,J=26.0Hz),54.9,53.8.19F NMR(376MHz,CDCl3):δ-61.6(s,3F).IR(KBr):3034,2955,2233,1762,1657,1599,1576,1535,1496,1481,1460,1438,1355,1318,1262,1208,1187,1116,1070,1012,971,939,927,916,858,832,798,757,726,697,646,585,537cm-1.HRMS(ESI)计算值calcd.for C26H20O3N2F3(M+H+):465.1421;实测值found:465.1416.
6)化合物3af 2-(8-(1-萘基)菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
172.2mg,收率67%,白色固体.熔点:152-153℃.1H NMR(400MHz,CDCl3):δ8.80(d,J=8.2Hz,1H),8.64(d,J=6.0Hz,1H),8.23(s,1H),8.16-8.12(m,1H),8.00-7.92(m,3H),7.83(d,J=8.6Hz,2H),7.77(d,J=5.4Hz,2H),7.61-7.55(m,2H),7.50-7.42(m,2H),4.41-4.28(m,2H),4.00-3.82(m,2H),3.94(s,3H).13C NMR(100MHz,CDCl3):δ164.9,161.2,151.3,142.2,139.5,139.2,133.8,133.0,132.7,131.5,130.9,128.8,128.48,128.47,128.3,127.9(q,J=4.2Hz),127.3,126.3,126.0,125.6,125.5,124.5,124.2,123.5(q,J=283.6Hz),122.6,121.9,68.5,68.2(q,J=26.2Hz),54.7,53.7.19F NMR(376MHz,CDCl3):δ-61.6(s,3F).IR(KBr):3059,2953,2924,2853,1756,1662,1576,1526,1508,1479,1458,1435,1395,1353,1317,1247,1209,1185,1114,1070,1042,973,926,911,868,839,802,792,779,762,743,729,701,682,668,652,618,582,572,538cm-1.HRMS(ESI)计算值calcd.for C30H22O3N2F3(M+H+):515.1577;实测值found:515.1580.
7)化合物3ag 2-(8-甲磺酰基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
165.5mg,收率71%,白色固体.熔点:197-198℃.1H NMR(400MHz,CDCl3):δ8.83(d,J=8.8Hz,1H),8.80(s,1H),8.59(d,J=8.0Hz,1H),8.29(dd,J=8.8,1.9Hz,1H),8.16(d,J=7.9Hz,1H),7.84(t,J=7.1Hz,1H),7.78(t,J=7.1Hz,1H),4.44(t,J=7.1Hz,2H),4.22-4.04(m,2H),4.00(s,3H).13C NMR(100MHz,CDCl3):δ164.3,160.6,151.3,143.1,138.6,137.1,131.1,130.6,129.2,128.1(q,J=3.5Hz),127.2,124.2,124.0,123.3(q,J=283.5Hz),123.0,122.4,68.8,67.6(q,J=26.0Hz),54.8,54.0,44.6.19F NMR(376MHz,CDCl3):δ-62.2(s,3F).IR(KBr):3027,2960,2927,1758,1663,1611,1574,1523,1480,1462,1434,1407,1359,1308,1247,1189,1151,1118,1099,1066,1040,1021,1010,972,961,927,878,832,799,755,724,698,667,646,583,565,547,500cm-1.HRMS(ESI)计算值calcd.for C21H18O5N2F3S(M+H+):467.0883;实测值found:467.0895.
8)化合物3ah 2-(8-甲氧羰基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
185.1mg,收率83%,白色固体.熔点:186-188℃.1H NMR(400MHz,CDCl3):δ8.89(s,1H),8.71(d,J=8.7Hz,1H),8.58(dd,J=8.1,1.6Hz,1H),8.41(dd,J=8.7,1.6Hz,1H),8.15-8.11(m,1H),7.82-7.71(m,2H),4.48-4.35(m,2H),4.19-4.04(m,2H),4.00(s,3H),3.99(s,3H).13C NMR(100MHz,CDCl3):δ166.3,164.6,161.0,151.7,142.9,136.8,131.0,130.0,129.9,129.4(q,J=3.4Hz),128.7,128.3,124.0,123.6,123.3(q,J=283.4Hz),122.9,122.4,68.6,67.7(q,J=26.3Hz),54.9,53.9,52.6.19F NMR(376MHz,CDCl3):δ-62.1(s,3F).IR(KBr):3079,2986,2945,2892,2851,1763,1720,1662,1619,1571,1533,1482,1462,1438,1411,1361,1319,1267,1211,1189,1167,1141,1122,1070,1039,1011,970,938,920,886,845,822,796,757,738,724,697,660,636,585,555,538cm-1.HRMS(ESI)计算值calcd.for C22H18O5N2F3(M+H+):447.1162;实测值found:447.1160.
9)化合物3ai 2-(8-三氟甲基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
205.2mg,收率90%,白色固体.熔点:157-158℃.1H NMR(400MHz,CDCl3):δ8.78(d,J=8.7Hz,1H),8.58(d,J=8.3Hz,1H),8.44(s,1H),8.15(dd,J=7.7,1.1Hz,1H),8.02(d,J=8.7Hz,1H),7.85-7.74(m,2H),4.45-4.34(m,2H),4.12-4.05(m,2H),3.98(s,3H).13C NMR(100MHz,CDCl3):δ164.5,161.0,151.2,142.7,136.0,131.0,130.0,129.0,128.7(q,J=32.6Hz),126.1(q,J=3.2Hz),124.6(m),123.9,123.8(q,J=270.7Hz),123.7,123.31(q,J=283.6Hz),123.29,122.2,68.6,67.8(q,J=26.3Hz),54.8,53.9.19F NMR(376MHz,CDCl3):δ-61.9(s,3F),-62.5(s,3F).IR(KBr):3653,3573,2956,2913,2889,1759,1665,1630,1614,1577,1538,1483,1455,1436,1410,1365,1336,1296,1252,1211,1190,1172,1144,1120,1085,1038,1010,974,941,931,915,886,863,834,798,762,743,725,698,682,650,634,599,584,561,537cm-1.HRMS(ESI)计算值calcd.for C21H15O5N2F6(M+H+):457.0981;实测值found:457.0981.
10)化合物3aj 2-(10-甲基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
62.3mg,收率31%,黄色固体.熔点:129-131℃.1H NMR(400MHz,CDCl3):δ8.80(d,J=8.6Hz,1H),8.14(dd,J=7.8,1.8Hz,1H),8.00(d,J=8.5Hz,1H),7.75-7.67(m,3H),7.56-7.52(m,1H),4.46-4.34(m,2H),4.10-4.05(m,2H).13C NMR(100MHz,CDCl3):δ165.2,161.5,151.9,143.2,135.8,134.7,133.5,131.2,128.0,127.3,126.4,126.2,125.8,125.4,124.8(q,J=3.7Hz),123.4(q,J=284.2Hz),68.4,68.2(q,J=25.8Hz),54.8,53.7,27.1.19F NMR(376MHz,CDCl3):δ-61.5(s,3F).IR(KBr):3368,2956,2882,1821,1757,1690,1662,1576,1527,1484,1459,1438,1382,1351,1309,1265,1192,1118,1104,1046,952,932,880,848,794,764,727,703,659,641,588,538cm-1.HRMS(ESI)计算值calcd.forC21H18O3N2F2(M+H+):403.1264;实测值found:403.1260.
11)化合物3ak 2-(8,10-二氟菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
99.7mg,收率47%,黄色固体.熔点:151-153℃.1H NMR(400MHz,CDCl3):δ8.91(d,J=7.9Hz,1H),8.16-8.11(m,1H),7.81-7.72(m,2H),7.65(d,J=10.0Hz,1H),7.38(ddd,J=13.1,8.2,2.5Hz,1H),4.51-4.38(m,2H),4.10-4.05(m,2H),3.96(s,3H).13C NMR(100MHz,CDCl3):δ164.6,161.3(dd,J=256.7,12.3Hz),161.0,159.8(dd,J=247.5,13.4Hz),149.9,142.0,131.0,129.4(d,J=2.5Hz),129.0(d,J=1.4Hz),126.9(dd,J=9.6,5.1Hz),126.0(d,J=24.6Hz),123.3(q,J=284.0Hz),121.5(dd,J=4.7,1.0Hz),120.6(dd,J=10.4,2.7Hz),108.0(dt,J=23.1,4.0Hz),107.3(t,J=27.3Hz),68.6,68.1(q,J=25.6Hz),54.8,53.9.19F NMR(376MHz,CDCl3):δ-61.3(s,3F),-103.9(m,1F),-108.9(q,J=9.6Hz,1F).IR(KBr):2957,2918,1764,1659,1634,1577,1529,1482,1458,1429,1410,1359,1324,1265,1208,1192,1170,1150,1126,1109,1048,1036,1020,1011,963,929,888,866,849,820,797,767,742,724,712,693,643,622,588,574,552,541,531cm-1.HRMS(ESI)计算值calcd.for C20H14O5N2F5(M+H+):425.0919;实测值found:425.0915.
12)化合物3al 2-(苯并呋喃[3,2-k]菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
121.9mg,收率51%,白色固体.熔点:198-199℃.1H NMR(400MHz,CDCl3):δ9.68(d,J=8.2Hz,1H),8.24-8.19(m,2H),8.15-8.08(m,2H),7.91-7.80(m,3H),7.61(t,J=7.8Hz,1H),7.47(t,J=7.5Hz,1H),4.50-4.36(m,2H),4.15-4.08(m,2H),3.97(s,3H).13C NMR(100MHz,CDCl3):δ165.1,161.5,156.8,152.4,151.1,142.6,130.6,129.0,128.7,128.2,127.0,125.1,124.1,123.6,123.5(q,J=283.8Hz),123.2,122.4,122.0,121.4(q,J=3.7Hz),121.0,119.3,112.2,68.5,68.3(q,J=26.0Hz),54.9,53.8.19F NMR(376MHz,CDCl3):δ-61.5(s,3F).IR(KBr):3065,2957,2921,1746,1660,1628,1607,1579,1569,1529,1493,1478,1456,1434,1418,1360,1341,1317,1275,1244,1217,1184,1102,1043,1032,1002,965,945,925,892,875,863,848,829,799,768,742,728,701,685,648,637,602,586,558,546,536,522cm-1.HRMS(ESI)计算值calcd.for C26H18O4N2F3(M+H+):479.1213;实测值found:479.1210.
13)化合物3am 2-(苯并噻吩[3,2-k]菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
133.4mg,收率54%,白色固体.熔点:192-195℃.1H NMR(400MHz,CDCl3):δ9.21(dd,J=8.5,1.2Hz,1H),8.47(d,J=8.9Hz,1H),8.37-8.32(m,1H),8.27-8.23(m,2H),8.09-8.04(m,1H),7.95-7.88(m,1H),7.87-7.82(m,1H),7.65-7.56(m,2H),4.50-4.37(m,2H),4.19-4.04(m,2H),3.96(s,3H).13C NMR(100MHz,CDCl3):δ165.1,161.5,151.6,143.1,140.3,137.4,134.6,134.2,131.4,130.8,128.7,128.6,127.8,125.25,125.17,124.3,123.8,123.5(q,J=284.1Hz),123.1(q,J=3.4Hz),122.4,122.2,120.5,68.5,68.3(q,J=26.0Hz),54.9,53.8.19F NMR(376MHz,CDCl3):δ-61.5(s,3F).IR(KBr):3064,2956,1747,1660,1598,1576,1521,1483,1457,1447,1434,1387,1347,1302,1244,1214,1187,1153,1108,1079,1037,1002,933,874,864,852,827,799,778,751,729,700,645,590,579,536,515cm-1.HRMS(ESI)计算值calcd.for C26H18O3N2F3S(M+H+):495.0985;实测值found:495.0980.
14)化合物3an 2-(噻蒽[2,1-k]喹啉-2-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
181.5mg,收率69%,浅黄色固体.熔点:159-162℃.1H NMR(400MHz,CDCl3):δ9.51-9.45(m,1H),8.16-8.11(m,1H),7.99(d,J=8.7Hz,1H),7.84-7.78(m,3H),7.63-7.55(m,2H),7.37-7.27(m,2H),4.46-4.30(m,2H),4.05(d,J=9.9Hz,2H),3.92(s,3H).13C NMR(100MHz,CDCl3):δ164.9,161.3,151.1,143.4,139.6,137.0,135.5,135.0,133.9,130.6,129.3,129.2,128.7,128.5,128.0,127.95,127.91,127.3,125.2(q,J=3.4Hz),125.1,123.34,123.31(q,J=284.1Hz),68.5,68.0(q,J=26.0Hz),54.8,53.8.19F NMR(376MHz,CDCl3):δ-61.4(s,3F).IR(KBr):3062,2952,1752,1667,1578,1505,1474,1450,1432,1370,1342,1270,1246,1212,1190,1152,1078,1033,1012,971,959,930,872,859,824,794,765,732,694,638,625,589,569,538,523,507cm-1.HRMS(ESI)计算值calcd.forC26H18O3N2F3S2(M+H+):527.0705;实测值found:527.0701.
15)化合物3ao 2-(9-甲基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
106.6mg,收率53%,白色固体.熔点:137-140℃.1H NMR(400MHz,CDCl3):δ8.55(dd,J=7.7,2.0Hz,1H),8.46(s,1H),8.10-8.06(m,1H),7.98(d,J=8.7Hz,1H),7.74-7.65(m,2H),7.46(dd,J=8.7,1Hz,1H),4.48-4.34(m,2H),4.12-4.05(m,2H).13C NMR(100MHz,CDCl3):δ165.1,161.4,151.1,142.3,140.9,134.2,130.8,128.7,128.6,128.0,126.4(q,J=3.8Hz),124.1,123.5(q,J=284.6Hz),122.6,122.2,121.8,68.4,68.0(q,J=26.3Hz),54.8,53.7,22.1.19F NMR(376MHz,CDCl3):δ-61.8(s,3F).IR(KBr):2956,1759,1655,1622,1575,1519,1498,1478,1459,1438,1385,1357,1313,1266,1250,1183,1115,1098,1070,1035,1007,932,880,818,797,761,728,719,701,652,633,622,580,524cm-1.MS(EI,m/z,%):402(M+,100),343(70.99),402(70.3).HRMS(EI)计算值calcd.for C21H17N2O3F3:402.1191;实测值found:402.1189.
16)化合物3ap 2-(7,9-二(三氟甲基)菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
238.5mg,收率91%,白色固体.熔点:64-67℃.1H NMR(400MHz,CDCl3):δ7.86-7.79(m,2H),7.51-7.45(m,1H),7.40-7.34(m,2H),7.01(d,J=7.9Hz,1H),4.39-4.24(m,2H),3.98-3.83(m,2H),3.75(s,3H).13C NMR(100MHz,CDCl3):δ161.9,158.8,145.4,140.5,131.4(q,J=33.2Hz),131.1,130.3,130.0,129.5,129.4,126.7,123.3(q,J=271.0Hz),121.3(q,J=284.4Hz),121.2(m),119.7,70.7(q,J=27.3Hz),68.8,54.4,54.0.19F NMR(376MHz,CDCl3):δ-62.8(s,3F),-62.9(s,6F).IR(KBr):3282,2961,2882,1759,1687,1667,1625,1597,1564,1489,1466,1435,1383,1360,1285,1250,1179,1118,1060,1038,1001,974,947,924,899,870,818,802,792,768,741,719,703,683,645,628,571,539,513cm-1.HRMS(ESI)计算值caldc.for C22H14O3N2F9(M+H+):525.0855;实测值found:525.0851.
17)化合物3aq 2-(2-甲基菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
144.8mg,收率72%,白色固体.熔点:111-113℃.1H NMR(400MHz,CDCl3):δ8.67(d,J=8.4Hz,1H),8.34(s,1H),8.07(d,J=8.6Hz,1H),7.98(d,J=8.3Hz,1H),7.81(t,J=7.6Hz,1H),7.62(t,J=7.4Hz,1H),7.55(d,J=8.3Hz,1H),4.48-4.32(m,2H),4.12-4.05(m,2H),3.95(s,3H),2.63(s,3H).13C NMR(100MHz,CDCl3):δ165.1,161.4,150.2,140.5,138.4,133.6,130.6,130.5,130.1,126.7,126.5(q,J=3.8Hz),124.5,124.0,123.5(q,J=284.0Hz),122.6,121.3,68.4,68.3(q,J=26.0Hz),68.0(q,J=26.0Hz),54.8,53.7,22.1.19F NMR(376MHz,CDCl3):δ-61.8(s,3F).IR(KBr):2954,1759,1662,1618,1575,1547,1523,1499,1479,1448,1436,1357,1343,1317,1266,1189,1141,1123,1098,1070,1037,1014,974,931,907,891,880,865,825,798,770,736,693,661,635,624,584,564,552,538,511cm-1.HRMS(ESI)计算值calcd.For C21H18O3N2F3(M+H+):403.1264;实测值found:403.1258.
18)化合物3ar 2-(2-氯菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
189.9mg,收率90%,黄色固体.熔点:133-135℃.1H NMR(400MHz,CDCl3):δ8.59(d,J=8.4Hz,1H),8.52(d,J=2.2Hz,1H),8.10(d,J=8.5Hz,1H),8.03(d,J=8.3Hz,1H),7.85(t,J=7.7Hz,1H),7.71-7.65(m,2H),4.49-4.35(m,2H),4.08(t,J=9.1Hz,2H),3.94(s,3H).13C NMR(100MHz,CDCl3):δ164.8,161.2,151.5,140.5,134.4,132.9,132.3,130.7,129.4,127.6,126.6(q,J=3.7Hz),125.3,124.7,123.3(q,J=284.0Hz),122.7,121.5,68.5,67.9(q,J=26.3Hz),54.8,53.8.19F NMR(376MHz,CDCl3):δ-61.7(s,3F).IR(KBr):3068,2958,2908,1748,1666,1604,1572,1523,1489,1446,1436,1354,1341,1317,1271,1249,1224,1180,1119,1090,1065,1036,974,960,927,874,855,831,798,765,742,725,684,670,655,629,619,587,560,539,514cm-1.HRMS(ESI)计算值calcd.for C20H15O3N2ClF3(M+H+):423.0718;实测值found:423.0712.
19)化合物3as 2-(2,4-二氟菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
133.6mg,收率63%,白色固体.熔点:157-160℃.1H NMR(400MHz,CDCl3):δ8.52(d,J=8.3Hz,1H),8.14(d,J=8.5Hz,1H),7.97(dt,J=9.8,2.1Hz,1H),7.90-7.84(m,1H),7.73(ddd,J=8.4,7.1,1.1Hz,1H),7.23(td,J=9.1,2.6Hz,1H),4.53-4.38(m,2H),4.08(t,J=9.6Hz,2H),3.97(s,3H).13C NMR(100MHz,CDCl3):δ164.8,161.5(dd,J=248.5,11.9Hz),161.2,159.3(dd,J=259.2,13.5Hz),150.9,132.9(dd,J=4.7,3.0Hz),131.0,129.2(dd,J=10.8,2.2Hz),128.2,127.0(dt,J=6.4,3.2Hz),126.8(d,J=2.2Hz),125.0,123.3(q,J=283.7Hz),123.1,104.5(dd,J=28.3,22.6Hz),102.7(dd,J=23.3,4.7Hz),68.6,68.2(q,J=26.9Hz),54.8,53.8.19F NMR(376MHz,CDCl3):δ-61.4(s,3F),-107.0(q,J=8.9Hz,1F),-117.6(m,1F).IR(KBr):3092,2959,1763,1667,1630,1586,1530,1497,1443,1418,1377,1354,1317,1258,1177,1134,1092,1065,1033,1012,1000,974,939,926,891,884,856,840,795,768,732,703,658,645,631,613,594,535,517,502cm-1.HRMS(ESI)计算值calcd.for C20H14O3N2F5(M+H+):425.0919;实测值found:425.0914.
20)化合物3at 2-(2-氟-3-氯菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
200.2mg,收率91%,浅黄色固体.熔点:189-190℃.1H NMR(400MHz,CDCl3):δ8.50(d,J=8.3Hz,1H),8.24(d,J=10.2Hz,1H),8.18(d,J=7.4Hz,1H),8.10(d,J=8.4Hz,1H),7.86(t,J=7.3Hz,1H),7.69(t,J=8.2Hz,1H),4.49-4.36(m,2H),4.11-4.04(m,2H),3.94(s,3H).13C NMR(100MHz,CDCl3):δ164.7,161.1,157.4(d,J=251.6Hz),151.9(d,J=3.1Hz),139.0(d,J=2.2Hz),133.0(d,J=4.1Hz),132.5,130.9,127.8,126.8(q,J=3.5Hz),124.5,124.3(d,J=8.0Hz),123.3(q,J=283.8Hz),123.1(d,J=20.4Hz),122.8,108.1(d,J=23.5Hz),68.6,67.8(q,J=26.2Hz),54.8,53.9.19F NMR(376MHz,CDCl3):δ-61.7(s,3F),-113.4(dd,J=10.1,7.4Hz,1F).IR(KBr):2952,1762,1665,1615,1571,1526,1488,1450,1436,1357,1324,1256,1184,1166,1136,1098,1071,1057,1035,1010,974,957,931,903,884,801,794,767,756,722,714,697,662,645,627,596,566,547,537cm- 1.HRMS(ESI)计算值calcd.for C20H14O3N2ClF4(M+H+):441.0624;实测值found:441.0624.
21)化合物3au 2-(2-硝基-3-氟菲啶-6-基)-2-(4,5-二氢-2-噁唑基)-3,3,3-三氟丙酸甲酯
162.4mg,收率72%,黄色固体.熔点:159-162℃.1H NMR(400MHz,CDCl3):δ9.30(d,J=7.5Hz,1H),8.65(d,J=8.3Hz,1H),8.16(d,J=8.5Hz,1H),7.99-7.94(m,2H),7.75(t,J=7.8Hz,1H),4.51-4.39(m,2H),4.07(t,J=9.8Hz,2H),3.93(s,3H).13C NMR(100MHz,CDCl3):δ164.4,160.8,156.5,155.9(d,J=263.0Hz),145.1(d,J=11.5Hz),137.4(d,J=10.0Hz),133.3,132.1,128.4,127.2(q,J=3.0Hz),124.7,123.1(q,J=284.1Hz),122.8,121.3(d,J=1.7Hz),120.7(d,J=2.9Hz),118.6(d,J=20.1Hz),68.7,67.8(q,J=26.3Hz),54.8,54.0.19F NMR(376MHz,CDCl3):δ-61.5(s,3F),-118.8(dd,J=11.1,7.5Hz,1F).IR(KBr):3311,3056,2956,2920,2850,1759,1663,1627,1584,1544,1523,1490,1452,1344,1322,1247,1217,1194,1154,1100,1039,1014,977,926,902,874,846,805,770,758,714,695,668,656,626,596,580,547cm-1.HRMS(ESI)计算值calcd.for C20H14O5N3F4(M+H+):452.0864;实测值found:452.0859.
22)化合物3ba(2-(6-菲啶基)-2-(4,4-二甲基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
162.1mg,收率75%,白色固体.熔点:139-142℃.1H NMR(400MHz,CDCl3):δ8.68(d,J=8.3Hz,1H),8.58-8.54(m,1H),8.16(d,J=8.5Hz,1H),8.12-8.08(m,1H),7.86-7.80(m,1H),7.76-7.67(m,2H),7.66-7.60(m,1H),4.08-4.00(m,2H),3.96(s,3H),1.41(s,3H),1.38(s,1H).13C NMR(100MHz,CDCl3):δ165.0,158.3,151.4,142.2,134.0,130.8,130.4,128.7,128.3,126.9(q,J=3.7Hz),126.6,124.5,124.2,123.5(q,J=283.6Hz),122.6,121.8,79.7,68.2,68.0(q,J=26.2Hz),53.6,54.0,27.62,27.58.19F NMR(376MHz,CDCl3):δ-61.6(s,3F).IR(KBr):3070,2972,2928,2895,1762,1663,1613,1575,1527,1489,1461,1446,1435,1385,1366,1350,1313,1291,1247,1217,1192,1114,1070,1038,1013,958,936,900,835,812,795,782,764,729,713,693,674,644,615,584,553,538cm-1.HRMS(ESI)计算值calcd.for C22H20O3N2F3(M+H+):417.1421;实测值found:417.1417.
23)化合物3ca(2-(6-菲啶基)-2-((S)-4-苄基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
193.7mg,收率81%.(三氟甲基连接季碳中心R.S构型尚未确定)
异构体1(3ca-1):黄色油状液体.1H NMR(400MHz,CDCl3):δ8.69(d,J=8.3Hz,1H),8.60-8.55(m,1H),8.15-8.08(m,2H),7.84(t,J=7.7Hz,1H),7.77-7.69(m,2H),7.63(t,J=7.8Hz,1H),7.31-7.18(m,5H),4.68-4.58(m,1H),4.26(t,J=8.9Hz,1H),4.16(t,J=8.0Hz,1H),3.93(s,3H),3.22(dd,J=13.7,4.8Hz,1H),2.78(dd,J=13.7,9.0Hz,1H).13CNMR(100MHz,CDCl3):δ164.9,160.7,151.3,142.2,137.4,134.0,130.8,130.4,129.4,128.8,128.6,128.3,126.82,126.76(q,J=3.9Hz),126.6,124.5,124.3,123.5(q,J=283.5Hz),122.6,121.8,72.4,68.1(q,J=27.3Hz),67.9,53.7,40.8.19F NMR(376MHz,CDCl3):δ-61.7(s,3F).IR(film):3063,3029,2952,2927,2854,1759,1661,1613,1576,1552,1528,1497,1488,1454,1445,1435,1350,1308,1272,1113,1093,1072,1033,1013,956,909,874,839,812,799,761,727,700,640,615,583,555,538,505cm-1.MS(EI,m/z,%):478(M+,3.72),91(100),149(80.93).HRMS(EI)计算值calcd.for C27H21N2O3F3:478.1504;实测值found:478.1500.
异构体2(3ca-2):无色油状液体.1H NMR(400MHz,CDCl3):δ8.68(d,J=8.2Hz,1H),8.59-8.54(m,1H),8.12-8.07(m,1H),7.93(d,J=8.6Hz,1H),7.82(t,J=7.7Hz,1H),7.76-7.68(m,2H),7.55-7.49(m,1H),7.37-7.23(m,5H),4.67-4.58(m,1H),4.34(t,J=9.0Hz,1H),4.08(t,J=8.0Hz,1H),3.95(s,3H),3.20(dd,J=13.8,4.8Hz,1H),2.92(dd,J=13.8,8.3Hz,1H).13C NMR(100MHz,CDCl3):δ165.0,160.7,151.2,142.2,137.2,133.9,130.8,130.4,129.7,128.8,128.6,128.3,126.8,126.7,124.5,124.2,123.4(q,J=283.5Hz),122.6,121.8,72.1,68.0(q,J=27.3Hz),67.7,53.7,40.5.19F NMR(376MHz,CDCl3):δ-61.7(s,3F).IR(film):3063,3028,2954,2926,2855,1760,1661,1614,1576,1527,1497,1488,1454,1445,1435,1350,1266,1113,1074,1047,1014,957,909,873,799,761,727,714,701,667,638,615,582,555,538,519,505cm-1.MS(EI,m/z,%):478(M+,47.11),387(100),91(54.68).HRMS(EI)计算值calcd.for C27H21N2O3F3:478.1504;实测值found:478.1511.
24)化合物3da(2-(6-菲啶基)-2-((R)-4-异丁基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
162.1mg,收率73%,无色油状液体.1H NMR(400MHz,CDCl3):δ8.68(d,J=8.4Hz,1H),8.59-8.54(m,1H),8.16-8.07(m,2H),7.83(t,J=7.7Hz,1H),7.76-7.68(m,2H),7.67-7.60(m,1H),7.37-7.23(m,5H),4.50-4.30(m,2H),4.06-3.93(m,4H),1.80-1.65(m,2H),1.50-1.36(m,1H),0.99-0.90(m,6H).13C NMR(100MHz,CDCl3):δ165.2,165.0,159.8,159.7,151.4,151.3,142.20,142.15,134.0,133.9,130.9,130.8,130.4,128.7,128.2,127.0(q,J=3.9Hz),126.71,126.66,126.62,124.6,124.5,124.3,124.2,123.49(q,J=283.7Hz),123.46(q,J=283.6Hz),122.6,122.5,121.8,73.8,73.7,68.2(q,J=26.1Hz),67.9(q,J=26.3Hz),65.3,65.2,44.7,25.4,25.3,23.0,22.9,22.5,22.4.19F NMR(376MHz,CDCl3):δ-61.5(s,1.5F),-61.8(s,1.5F).IR(film):3080,3026,2990,2901,1951,1903,1691,1656,1582,1526,1473,1447,1399,1300,1287,1211,1184,1160,1113,1049,1024,1008,963,949,941,878,860,840,823,758,742,680,654,640,582,574,551,528,508cm- 1.HRMS(ESI)计算值calcd.for C24H24O3N2F3(M+H+):445.1734;实测值found:445.1731.
25)化合物3ea(2-(6-菲啶基)-2-((S)-4-仲丁基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
157.7mg,收率71%,无色油状液体.1H NMR(400MHz,CDCl3):δ8.68(d,J=8.3Hz,1H),8.56(d,J=8.5Hz,1H),8.17-8.07(m,2H),7.83(t,J=7.6Hz,1H),7.76-7.68(m,2H),7.66-7.59(m,1H),4.42-4.25(m,2H),4.20-4.08(m,1H),3.95(s,1.5H),3.92(s,1.5H),1.88-1.75(m,1H),1.58-1.43(m,1H),1.30-1.10(m,1H),0.97-0.87(m,6H).13C NMR(100MHz,CDCl3):δ165.1,165.0,159.8,159.6,151.4,142.20,142.16,133.93,133.86,130.9,130.8,130.38,130.35,128.7,128.3,128.2,127.3(q,J=4.0Hz),126.8(q,J=3.6Hz),126.7,124.5,124.25,124.20,123.5(q,J=284.4Hz),122.6,122.5,121.78,121.77,71.1,71.0,70.00,69.98,67.9(q,J=26.0Hz),67.8(q,J=26.5Hz),53.6,53.5,38.6,38.5,26.2,26.1,14.3,14.2,11.7,11.6.19F NMR(376MHz,CDCl3):δ-61.6(s,1.5F),-61.7(s,1.5F).IR(film):3075,2969,2901,2253,1750,1717,1699,1668,1653,1615,1576,1558,1527,1506,1488,1472,1456,1446,1436,1394,1381,1350,1250,1192,1110,1045,956,906,870,841,799,760,726,692,668,639,615,584,538cm-1.HRMS(ESI)计算值calcd.for C24H24O3N2F3(M+H+):445.1734;实测值found:445.1730.
26)化合物3fa(2-(6-菲啶基)-2-((R)-4-苯基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
167.1mg,收率72%,无色油状液体.1H NMR(400MHz,CDCl3):δ8.68(t,J=7.8Hz,1H),8.60–8.54(m,1H),8.20(d,J=8.5Hz,1H),8.16–8.11(m,1H),7.87-7.79(m,1H),7.78–7.68(m,2H),7.67-7.57(m,1H),7.44–7.27(m,5H),5.49-5.42(m,1H),4.88-4.74(m,1H),4.38-4.25(m,1H),4.00(s,1.5H),3.99(s,1.5H).13C NMR(100MHz,CDCl3):δ165.1,161.7,161.6,151.3,151.2,142.1,141.41,141.39,134.0,133.9,130.8,130.7,130.45,130.39,128.79,128.75,128.68,128.32,128.29,127.74,127.71,126.9,126.8(q,J=6.4Hz),126.7,124.42,124.37,123.49(q,J=283.8Hz),123.47(q,J=283.8Hz),122.6,121.84,121.79,121.77,75.67,75.65,70.0,69.7,68.4(q,J=26.4Hz),68.2(q,J=26.2Hz),53.74,53.70.19F NMR(376MHz,CDCl3):δ-61.2(s,1.5F),-61.4(s,1.5F).IR(film):3470,3384,3072,3023,2920,2850,1734,1717,1669,1653,1614,1577,1559,1533,1515,1482,1454,1396,1352,1295,1264,1158,1105,1073,1006,915,845,833,755,745,702,686,618,573,518cm-1.MS(EI,m/z,%):444(M+,22.95),301(100),104(29.92).HRMS(EI)计算值calcd.for C26H19N2O3F3:464.1348;实测值found:464.1339.
27)化合物3ga(2-(6-菲啶基)-2-((S)-4-异丙基-4,5-二氢噁唑-2-基)-3,3,3-三氟丙酸甲酯)
157.0mg,收率73%,无色油状液体.1H NMR(400MHz,CDCl3):δ8.68(d,J=8.4Hz,1H),8.59–8.54(m,1H),8.18-8.07(m,2H),7.83(t,J=7.7Hz,1H),7.76-7.68(m,2H),7.62(t,J=7.8Hz,1H),4.44-4.29(m,1H),4.21-4.08(m,2H),3.95(s,1.5H),3.92(s,1.5H),2.02-1.87(m,1H),1.03-0.91(m,6H).13C NMR(100MHz,CDCl3):δ165.2,165.0,160.0,159.7,151.4,142.22,142.17,134.0,133.9,130.9,130.8,130.38,130.35,128.7,128.3,128.2,127.0(q,J=4.2Hz),126.8(q,J=3.8Hz),126.7,124.5,124.3,124.2,123.49(q,J=283.6Hz),123.48(q,J=283.6Hz),122.6,122.5,121.79,121.78,72.5,72.4,70.64,70.61,68.3(q,J=26.3Hz),67.9(q,J=26.4Hz),53.6,53.5,32.4,32.3,18.9,18.8,18.1,18.0.19F NMR(376MHz,CDCl3):δ-61.6(s,1.5F),-61.7(s,1.5F).IR(film):cm-1..IR(film):3074,2959,2875,1759,1664,1614,1576,1528,1488,1462,1445,1435,1387,1349,1266,1213,1192,1114,1072,1040,1016,952,905,871,838,800,762,727,715,690,638,615,585,556,538cm-1.HRMS(ESI)for C23H22O3N2F3:(M+H+):Calcd:431.1577;Found:431.1574.
实施例5生物活性测试
(1)杀菌活性测试
测定对象:黄瓜霜霉病。
测定方法:取温室内培养的生长一致的两叶期黄瓜,编号后备用。准确称取样品,加入溶剂和0.1%的吐温-80自来水后,配制成400mg/L的药液各20ml,用于杀菌活性测定。对照药剂代森锰锌、嘧菌酯的浓度为为25mg/L。采用作物喷雾机进行喷雾处理(喷雾器类型为立体作物喷雾机,喷雾压力为1.5kg/cm2,喷液量约为675L/hm2)上述试验材料,处理后,另设清水处理作为空白对照,自然风干,24h后接种病原菌。采用接种器分别将黄瓜霜霉病菌孢子囊悬浮液(5×105个/ml)喷雾于寄主作物上,然后移入人工气候室培养(24℃,RH>90,无光照)。24h后,试验材料移于温室正常管理,4-7天后调查试验样品的杀菌活性。
根据对照的发病程度,采用目测方法,调查试验样品的杀菌活性,结果用100-0来表示,以“100”级代表无病,“0”级代表最严重的发病程度,并以空白对照为最严重发病程度,即为“0”级发病程度。
表5-1杀菌活性测试结果
参见表5-1,测试结果表明,化合物3ab、3ac、3ae、3ag、3ah、3ai、3ak、3al、3ao、3au、3da对黄瓜霜霉病的防治效果为100%,3ba、3ca-1对该病害的防治效果在95-98%之间,3am、3aq、3as、3at、3ba、3ea、3fa、3ga对该病害具有一定防治效果。
(2)杀虫活性测试
测试对象:小菜蛾和桃蚜。
测试方法:
(一)小菜蛾的测试方法:在培养皿(Ф=6cm)底覆一层滤纸,滴加适量自来水保湿,备用。取温室培养的甘蓝叶片,除去表面蜡质层,用打孔器制成甘蓝叶碟(Ф=3cm),叶背向上置于培养皿中。按试验设计,用Airbrush手持式喷雾设备将600mg/L化合物待测液(溶剂和0.1%的吐温-80自来水配制)均匀喷雾于叶片正反面(喷雾压力:0.7kg/cm2,喷液量:0.5ml;喷雾距离:15-20cm),另设清水处理作为空白对照。待叶片自然阴干后,接入小菜蛾3龄幼虫。将培养皿移至标准观察室内(温度为23-25℃,RH=40-60%,L/D为13h/11h)培养,72h后进行调查,记录试虫的死虫与活虫数,计算死亡率。
(二)桃蚜的测试方法:从培养桃蚜的甘蓝植株上剪取大小适宜且长有30-50头桃蚜的甘蓝叶片,去除翅蚜及正面的蚜虫,叶背向上置于培养皿内,作为测定寄主和靶标,其它方法同前。
表5-2杀虫活性测试结果
药剂 | 小菜蛾 | 桃蚜 | 备注 |
3aa | 0 | 33.3 | 600mg/L |
3ac | 0 | 54.5 | 600mg/L |
3ah | 42.9 | 31.3 | 600mg/L |
3ba | 0 | 60.0 | 600mg/L |
3ca-2 | 0 | 50.0 | 600mg/L |
3da | 28.6 | 0 | 600mg/L |
3fa | 0 | 37.1 | 600mg/L |
参见表5-2,测试结果表明,本发明化合物3ah、3da对小菜蛾有一定活性;而本发明化合物3aa、3ac、3ah、3ba、3ca-2、3fa对桃蚜具有一定活性。
(3)除草活性测试
测试对象:百日草、苘麻。
测试方法:将定量的阔叶杂草(百日草、苘麻)种子分别播于装有营养土的纸杯(Ф=7cm)中,覆土1cm,镇压、淋水后在温室内培养。阔叶杂草长至2叶期时,进行苗后茎叶喷雾处理。按试验设计,用Airbrush手持式喷雾设备将1000g a.i./hm2化合物待测液(溶剂和0.1%的吐温-80自来水配制)均匀喷雾于试材上(喷雾压力:0.7kg/cm2,喷液量:0.5mL;喷雾距离:15-20cm),另设清水处理作为空白对照。处理后的试材置于大厅内,待药液自然阴干后,放于温室内并继续培养。14d后,目测调查供试药剂对杂草的防除效果。结果用100-0来表示,以“100”级代表对杂草防除效果最好,“0”级代表对杂草无防除效果,并以空白对照中杂草情况为对杂草无防除效果即“0”级的效果。
表5-3除草活性测试结果
药剂 | 百日草 | 苘麻 | 备注 |
3ae | 20 | 10 | 1000g a.i./hm2 |
3af | 10 | 5 | 1000g a.i./hm2 |
3ag | 10 | 0 | 1000g a.i./hm2 |
3ah | 50 | 0 | 1000g a.i./hm2 |
3al | 10 | 0 | 1000g a.i./hm2 |
3ca-1 | 5 | 0 | 1000g a.i./hm2 |
3ca-2 | 15 | 0 | 1000g a.i./hm2 |
3da | 5 | 10 | 1000g a.i./hm2 |
3ga | 20 | 0 | 1000g a.i./hm2 |
参见表5-3,测试结果表明,本发明部分化合物对百日草、苘麻、金狗尾和稗草具有有一定除草活性。
在本发明提及的所有文献都在本申请中引用作为参考,就如同每一篇文献被单独引用作为参考那样。此外应理解,在阅读了本发明的上述讲授内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
Claims (10)
1.一种如式3所示的化合物或其对映异构体或非对映异构体或其混合物,或其盐:
其中,
R6为C1-C4烷基;
环Ar1为苯环,且所述苯环被一个或多个R4基团取代,R4独立地选自下组:H、卤素、-NO2、取代或未取代的C1-C6烷基、取代或未取代的C1-C4烷氧基、取代或未取代的C1-C4烷硫基、取代或未取代的C1-C5酰基、取代或未取代的C1-C5酯基;
环Ar2如式2.2所示:
其中,各个R5独立地选自下组:H、卤素、取代或未取代的C1-C6烷基、取代或未取代的C3-C12环烷基、取代或未取代的C1-C4烷氧基、取代或未取代的C1-C4烷硫基、取代或未取代的C6-C20芳基、取代或未取代的C3-C20杂芳基、取代或未取代的C1-C4烷基磺酰基、取代或未取代的C1-C5酯基、取代或未取代的C1-C5酰基;且n=1、2、3或4;
环A选自下组:无、取代或未取代的5到12元碳环、或取代或未取代的5到12元杂环;所述杂环为环上一个或多个碳原子被杂原子替换,且所述杂原子各自独立地选自:O、N或S;
各个R3独立地选自下组:H、取代或未取代的C1-C6烷基、取代或未取代的C6-C20芳基、取代或未取代的C6-C12芳基-C1-C4烷基;且z=1、2、3或4;
所述的取代是指基团上的氢被选自下组的取代基取代:卤素、C1-C3烷基、羟基、氨基、-NO2。
2.如权利要求1所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐,其特征在于,环Ar2具有如式2.2.1所示结构,或具有如式2.2.2所示结构:
(i)R5及n的定义同权利要求1;
或
(ii)
其中,环B为5到7元杂环,或5到7元碳环。
3.如权利要求1所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐,其特征在于,所述化合物具有式3.1所示结构
其中,R1及R2独立地选自下组:H、取代或未取代的C1-C6烷基、取代或未取代的C6-C20芳基、取代或未取代的C6-C12芳基-C1-C4烷基。
4.如权利要求1所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐,其特征在于,式3化合物选自下表所示化合物:
5.一种制备如权利要求1所述化合物或其对映异构体或非对映异构体或其混合物,或其盐的方法,其特征在于,在有机溶剂中,在催化剂和碱存在时,在可见光照射下,将式1化合物及式2化合物进行反应,从而形成式3化合物:
其中,环Ar1、环Ar2、R3、R6及z的定义如权利要求1所述;
X为F、Cl、Br或I。
6.如权利要求5所述的方法,其特征在于,所述方法包括步骤:
(1)提供一种反应体系,
所述反应体系包括式1化合物、式2化合物、催化剂、碱及有机溶剂;
(2)所述反应体系在可见光照射下进行反应,得到式3化合物。
7.如权利要求5所述的方法,其特征在于,所述碱选自下组:甲醇钠、叔丁醇钾、碳酸钠、碳酸钾、或其组合。
8.如权利要求5所述的方法,其特征在于,所述催化剂选自下组:三联吡啶氯化钌六水合物、三(2-苯基吡啶)铱(III)、二(2-苯基吡啶)(4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐、二[2-(2,4-二氟苯基)-5-(三氟甲基)吡啶](4,4’-二叔丁基-2,2’-联吡啶)铱(III)六氟磷酸盐、或其组合。
9.一种农药组合物,其特征在于,所述农药组合物包含如权利要求1所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐。
10.如权利要求1所述的化合物或其对映异构体或非对映异构体或其混合物,或其盐或如权利要求9所述农药组合物的用途,其特征在于,用于杀菌、杀虫或除草。
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