CN115160216B - 一种含吡啶结构的酰肼类化合物及其制备和应用 - Google Patents
一种含吡啶结构的酰肼类化合物及其制备和应用 Download PDFInfo
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- CN115160216B CN115160216B CN202210672674.0A CN202210672674A CN115160216B CN 115160216 B CN115160216 B CN 115160216B CN 202210672674 A CN202210672674 A CN 202210672674A CN 115160216 B CN115160216 B CN 115160216B
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- compound
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- hydrogen
- branched alkyl
- pyridine
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 80
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 230000000844 anti-bacterial effect Effects 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003899 bactericide agent Substances 0.000 claims description 13
- -1 methoxy, ethoxy, n-propoxy Chemical group 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 229940125782 compound 2 Drugs 0.000 claims description 8
- 229940126214 compound 3 Drugs 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- 241000123650 Botrytis cinerea Species 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 235000007164 Oryza sativa Nutrition 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 235000009566 rice Nutrition 0.000 claims description 3
- VXNQJPMCJMJOMN-UHFFFAOYSA-N 1,1-difluoroethane Chemical compound C[C](F)F VXNQJPMCJMJOMN-UHFFFAOYSA-N 0.000 claims description 2
- 241000223600 Alternaria Species 0.000 claims description 2
- 241000222199 Colletotrichum Species 0.000 claims description 2
- 241000223218 Fusarium Species 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 claims description 2
- FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 claims description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- BNHFWQQYLUPDOG-UHFFFAOYSA-N lithium;1,2,2,3-tetramethylpiperidine Chemical compound [Li].CC1CCCN(C)C1(C)C BNHFWQQYLUPDOG-UHFFFAOYSA-N 0.000 claims description 2
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 claims description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 238000000034 method Methods 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 240000008042 Zea mays Species 0.000 claims 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 235000005822 corn Nutrition 0.000 claims 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000361 pesticidal effect Effects 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229960003975 potassium Drugs 0.000 claims 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 abstract description 3
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 11
- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 description 11
- 239000006013 carbendazim Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000005783 Fluopyram Substances 0.000 description 9
- KVDJTXBXMWJJEF-UHFFFAOYSA-N fluopyram Chemical compound ClC1=CC(C(F)(F)F)=CN=C1CCNC(=O)C1=CC=CC=C1C(F)(F)F KVDJTXBXMWJJEF-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000813090 Rhizoctonia solani Species 0.000 description 4
- 241000209140 Triticum Species 0.000 description 4
- 235000021307 Triticum Nutrition 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 241001290235 Ceratobasidium cereale Species 0.000 description 3
- 240000008067 Cucumis sativus Species 0.000 description 3
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- PXMNMQRDXWABCY-UHFFFAOYSA-N 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol Chemical compound C1=NC=NN1CC(O)(C(C)(C)C)CCC1=CC=C(Cl)C=C1 PXMNMQRDXWABCY-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 241000223195 Fusarium graminearum Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001330975 Magnaporthe oryzae Species 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000005839 Tebuconazole Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YOYAIZYFCNQIRF-UHFFFAOYSA-N 2,6-dichlorobenzonitrile Chemical compound ClC1=CC=CC(Cl)=C1C#N YOYAIZYFCNQIRF-UHFFFAOYSA-N 0.000 description 1
- AJPOOWWMZOPUCG-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=NC=C(C(F)(F)F)C=C1Cl AJPOOWWMZOPUCG-UHFFFAOYSA-N 0.000 description 1
- 241000223602 Alternaria alternata Species 0.000 description 1
- 241001558165 Alternaria sp. Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241001529387 Colletotrichum gloeosporioides Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241001103573 Germaria Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001344131 Magnaporthe grisea Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001115351 Physalospora Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
本发明涉及一种式I‑1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐及其制备方法,以及其作为植物抗菌剂中的应用。
Description
技术领域
本发明涉及一种酰肼类化合物,属于植物杀菌剂技术领域,具体地涉及一种含吡啶结构的酰肼类化合物及其制备方法与应用。
背景技术
杀菌剂作为重要的农业生产资料,在保障粮食安全、农产品质量和生态环境安全等方面发挥着重要作用。杀菌剂抗性行动委员会(FRAC)报道已经商品化的杀菌剂品种近乎224种,然而随着传统杀菌剂的长期大量使用,抗药性问题日益突出,新型杀菌剂的开发是解决上述问题的有效途径。
先导化合物的发现和作用靶标的探索是创新杀菌剂研究的关键。为了开发结构新颖的高效杀菌剂,以文献报道的具有杀菌活性的酰肼基团和前期工作中发现的具有优异杀菌活性的吡啶硫醚结构(Hua et al.Engineering,2020,6,553;Hua et al.PestManag.Sci.,2020,76,2368)为母体骨架,首次设计合成了系列结构新颖的含吡啶结构的酰肼类化合物,生物活性测试发现目标化合物显示出与对照药多菌灵、氟吡菌酰胺相当甚至优于对照药的杀菌活性,该结果对于探索新型绿色杀菌剂具有重要的指导意义。但是现有技术中杀菌剂仍然存在一定不足,亟需一种全新结构的杀菌剂化合物。
发明内容
为解决上述技术问题,本发明公开了一种含吡啶结构的酰肼类化合物及其制备方法与应用,并测试了化合物的杀菌活性。
本发明提供了一种式I-1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐,具备如下化学结构式:
其中,式I-1中基团X选自硫、氧或氮原子;
R1,R2,R3,R4,R5,R6,R7,R8,R9选自以下基团:氢、卤素、氨基、硝基、氰基、C1-C6直链或支链烷基、卤代C1-C6直链或支链烷基、羟基取代的C1-C6直链或支链烷基、C1-C6烷氧基、卤代C1-C6烷氧基、C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷氧基羰基、C3-C6环烷基、卤代C3-C6环烷基、N,N-(C1-C6烷基)氨基甲酰基、C6-C12芳基、C6-C12杂芳基中任意一种。
作为优选,其中所述卤代C1-C6直链或支链烷基、卤代C1-C6烷氧基、卤代C1-C6烷硫基、卤代C3-C6环烷基中的氢原子被部分或全部卤原子取代。
作为进一步优选,所述卤素和/或卤代原子为氟、氯、溴或碘中任意一种。
作为优选,所述的C1-C6直链或支链烷基选自甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、新戊基或己基;所述的C1-C6烷氧基选自甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、正戊氧基、异戊氧基、新戊氧基或己氧基,所述的卤代卤代C1-C6直链或支链烷基选自CFH2-、CF2H-、CF3-、CH3CFH-、CH3CF2-或CH3CF2-。
本发明还提供了一种上述式I-1所示的含吡啶结构的酰肼类化合物其农学上可接受的盐的制备方法,它包括如下步骤:
(1)吡啶化合物1溶解到有机溶剂中,与氯乙酸甲酯反应,制备得到含吡啶的酯类化合物2;其中化合物1和化合物2的化学结构式如下:
(2)含吡啶的酯类化合物2溶解到混合溶剂中,经碱水解制备含吡啶的羧酸化合物3;化合物3溶解到有机溶剂中,在缩合剂条件下,与芳香肼类化合物4反应,制备含吡啶的酰肼类化合物I-1;其中,化合物3、化合物4和目标化合物I-1的化学结构式如下:
其中,化合物1、化合物2、化合物3、化合物4和式I-1中基团X、R1,R2,R3,R4,R5,R6,R7,R8,R9定义与上述定义相同。
作为优选,步骤(1)或步骤(2)中的有机溶剂选自N,N-二甲基甲酰胺、乙醇、乙酸乙酯、甲醇、甲苯、DMSO、丙酮、水中、甲基叔丁基醚、乙醚中的一种或多种,优选为N,N-二甲基甲酰胺;步骤(2)中的混合溶剂为N,N-二甲基甲酰胺、乙醇、乙酸乙酯、甲醇、甲苯、DMSO、丙酮、水中的两种或多种,优选为甲醇和水。
作为进一步优选,步骤(2)中碱选自有机碱或无机碱,无机碱选自钠氢,碳酸钠,碳酸钾,碳酸铯,碳酸氢钠,碳酸氢钾,氢氧化钠,氢氧化钾,氢氧化锂或氢氧化钡一种或两种或多种;有机碱选自N,N-二异丙基乙胺、三乙胺、二异丙基酰胺锂、正-(C1-6烷基)锂、六甲基二硅氮烷锂、六甲基二硅氮烷钾、六甲基二硅氮烷钠、四甲基哌啶锂、丁氧基钾、戊氧基钾、戊醇钾一种或两种或多种。
作为进一步优选,所述步骤(2)中的缩合剂选自1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和4-二甲氨基吡啶。
本发明还提供了一种农药试剂,其包含至少一种固体或液体载体和根据上述式I-1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐。
本发明还提供了所述式I-1所示的含吡啶结构的酰肼类化合物在制备抗菌剂中的用途,优选作为植物抗菌剂。
以下为对本发明的名词术语的解释和说明:
本发明中提供的化合物和衍生物可以根据IUPAC(国际纯粹与应用化学联合会)或CAS(化学文摘服务社,Columbus,OH)命名系统命名。
关于本发明的使用术语的定义:除非另有说明,本文中基团或者术语提供的初始定义适用于整篇说明书的该基团或者术语;对于本文没有具体定义的术语,应该根据公开内容和上下文,给出本领域技术人员能够给予它们的含义。
“取代”是指分子中的氢原子被其它不同的原子或分子所替换。
碳氢基团中碳原子含量的最小值和最大值通过前缀表示,例如,前缀Ca~b烷基表明任何含“a”至“b”个碳原子的烷基。因此,例如,“C1~4烷基”是指包含1~4个碳原子的烷基。
“烷基”是指具有指定数目的成员原子的饱和烃链。例如,C1~6烷基是指具有1至6个成员原子,例如1至4个成员原子的烷基基团。烷基基团可以是直链或支链的。代表性的支链烷基基团具有一个、两个或三个支链。烷基基团可任选地被一个或多个如本文所定义的取代基取代。烷基包括甲基、乙基、丙基(正丙基和异丙基)、丁基(正丁基、异丁基和叔丁基)、戊基(正戊基、异戊基和新戊基)和己基。烷基基团也可以是其他基团的一部分,所述其他基团为例如C1~C6烷氧基。
“环烷基”是指具有碳原子且没有环杂原子且具有单个环或多个环(包括稠合、并和)的饱和或部分饱和的环状基团。对于具有不含环杂原子的芳族和非芳族环的多环体系,当连接点位于非芳族碳原子时,适用术语“环烷基”(例如5,6,7,8,-四氢化萘-5-基)。术语“环烷基”包括环烯基基团,诸如环己烯基。环烷基基团的实例包括例如,金刚烷基、环丙基、环丁基、环己基、环戊基、环辛基、环戊烯基和环己烯基。包括多双环烷基环体系的环烷基基团的实例是双环己基、双环戊基、双环辛基等。
“卤素”为氟、氯、溴或碘。
“卤素烷基”指烷基中的氢原子可被一个或多个卤素原子取代。例如C1~4卤素烷基指氢原子被一个或多个卤素原子取代的包含1~4个碳原子的烷基。
本发明的化合物可以包含不对称中心或手性中心,因此存在不同的立体异构体。本发明的化合物所有的立体异构形式,包括但绝不限于,非对映体,对映异构体,阻转异构体,和它们的混合物,如外消旋混合物,组成了本发明的一部分。很多有机化合物都以光学活性形式存在,即它们有能力旋转平面偏振光的平面。在描述光学活性化合物时,前缀D、L或R、S用来表示分子手性中心的绝对构型。这些立体异构体的化学结构是相同的,但是它们的立体结构不一样。特定的立体异构体可以是对映体,异构体的混合物通常称为对映异构体混合物。50:50的对映体混合物被称为外消旋混合物或外消旋体,这可能导致化学反应过程中没有立体选择性或立体定向性。术语“外消旋混合物”和“外消旋体”是指等摩尔的两个对映异构体的混合物,缺乏光学活性。
术语“农学上可接受的盐”是指上述化合物或其立体异构体,与无机和/或有机酸和碱形成的酸式和/或碱式盐,也包括两性离子盐(内盐),还包括季铵盐,例如烷基铵盐。这些盐可以是在化合物的最后分离和纯化中直接得到。也可以是通过将上述化合物,或其立体异构体,与一定数量的酸或碱适当(例如等当量)进行混合而得到。这些盐可能在溶液中形成沉淀而以过滤方法收集,或在溶剂蒸发后回收而得到,或在水介质中反应后冷冻干燥制得。本发明中所述盐可以是化合物的盐酸盐、硫酸盐、枸橼酸盐、苯磺酸盐、氢溴酸盐、氢氟酸盐、磷酸盐、乙酸盐、丙酸盐、丁二酸盐、草酸盐、苹果酸盐、琥珀酸盐、富马酸盐、马来酸盐、酒石酸盐或三氟乙酸盐。
在某些实施方式中,本发明的一种或多种化合物可以彼此联合使用。也可选择将本发明的化合物与任何其它的活性试剂结合使用。显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
本发明的有益效果在于:
1、本发明提供了一种含吡啶结构的酰肼类化合物,以文献报道的具有杀菌活性的酰肼基团和前期工作中发现的具有优异杀菌活性的吡啶硫醚结构为母体骨架,首次设计合成了系列结构新颖的含吡啶结构的酰肼类化合物,本发明化合物具备良好的杀菌活性,部分化合物对特定植物病原菌显示出优于商品化药剂多菌灵、氟吡菌酰胺的抑菌率,该结果对于探索新型高效杀菌剂具有重要的指导意义。
2、离体杀菌活性结果表明,本发明化合物显示出了优异的广谱杀菌活性,化合物I-4对玉米纹枯病菌、小麦赤霉病菌、黄瓜灰霉病菌以及苹果炭疽病菌均显示出优异的抑菌活性,并且对黄瓜灰霉病菌和苹果炭疽病菌的抑菌活性明显优于商品化药剂多菌灵和氟吡菌酰胺。此外,本发明化合物对苹果轮纹病菌的抑制效果均弱于多菌灵。从构效关系分析,苯环4位取代基为吸电子基时的抑菌活性优于供电子基,尤其以F取代时抑菌活性最佳。例如,化合物I-4和I-14均表现出优于其他化合物的广谱抑菌活性。
附图说明
图1为化合物在50μg/mL对玉米纹枯病菌的抑制效果,其中,图A1为空白对照;图A2为商品药多菌灵处理;图A3为商品药氟吡菌酰胺处理;图A4为化合物I-1处理;图A5为化合物I-4处理;图A6为化合物I-14处理;
图2为化合物在50μg/mL对小麦赤霉病菌的抑制效果,其中,图B1为空白对照;图B2为商品药多菌灵处理;图B3为商品药氟吡菌酰胺处理;图B4为化合物I-4处理;图B5为化合物I-5处理;图B6为化合物I-14处理;
图3为化合物在50μg/mL对黄瓜灰霉病菌的抑制效果,其中,图C1为空白对照;图C2为商品药多菌灵处理;图C3为商品药氟吡菌酰胺处理;图C4为化合物I-4处理;图C5为化合物I-5处理;图C6为化合物I-8处理;
图4为化合物在50μg/mL对苹果炭疽病菌的抑制效果,其中,图D1为空白对照;图D2为商品药多菌灵处理;图D3为商品药氟吡菌酰胺处理;图D4为化合物I-4处理;图D5为化合物I-8处理;图D6为化合物I-14处理。
图5为化合物在50μg/mL对水稻稻瘟病菌的抑制效果,其中,图E1为空白对照;图E2为商品药戊唑醇处理;图E3为商品药多菌灵处理;图E4为商品药氟吡菌酰胺处理;图E5为化合物I-8处理;图E6为化合物I-18处理。
具体实施方式
以下结合实施例来进一步说明本发明,其目的是能更好的理解本发明的内容及体现本发明的实质性特点,因此所举之例不应视为对本发明保护范围的限制。
实施例1
2-(((3-氯-5-三氟甲基)吡啶-2-基)氧代)乙酸甲酯的合成:
将3-氯-5三氟甲基吡啶-2-酚(3.00g,15.2mmol)、氯乙酸甲酯(1.81g,16.7mmol)、碳酸钾(2.74g,19.8mmol)加入到N,N-二甲基甲酰胺(30mL)中,将体系加热升温至80℃反应4小时,TLC监测反应。待反应完成后,将体系倒入乙酸乙酯(200mL)和水(200mL)的混合溶液中,取乙酸乙酯层,经无水硫酸钠干燥,过滤。滤液真空减压浓缩除去溶剂乙酸乙酯,剩余物通过柱层析纯化得到白色固体产物,洗脱液为石油醚:乙酸乙酯,体积比为3:1,收率90%。
实施例2
2-(((3-氯-5-三氟甲基)吡啶-2-基)氧代)乙酸的合成:
将2-(((3-氯-5-三氟甲基)吡啶-2-基)氧代)乙酸甲酯(4.00g,14.9mmol)溶解到甲醇(50mL)和水(5mL)的混合溶液中,加入氢氧化锂(1.07g,44.7mmol),室温搅拌2小时,TLC监测反应进程。反应完成后,真空浓缩除去溶剂,剩余物溶解到水(5mL)中,用稀盐酸调节pH至弱酸性。此时,如有固体析出,直接过滤;如无固体析出,真空浓缩除去部分溶剂后,有固体析出,过滤,滤饼干燥即得白色固体产物,收率75%。
实施例3
2-(((3-氯-5-三氟甲基)吡啶-2-基)氧代)-N'-苯基乙酰肼的合成:
将2-(((3-氯-5-三氟甲基)吡啶-2-基)氧代)乙酸(0.50g,2.0mmol)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.42g,2.2mmol)、4-二甲氨基吡啶(0.32g,2.6mmol)溶解到N,N-二甲基甲酰胺(15mL)中,然后加入苯肼(0.24g,2.2mmol),室温搅拌6小时,TLC监测反应进程。反应完成后,将体系倒入二氯甲烷(100mL)和水(100mL)的混合溶液中,取二氯甲烷层,经无水硫酸钠干燥,过滤。滤液真空减压浓缩除去溶剂二氯甲烷,剩余物通过柱层析纯化得到白色固体产物,洗脱液为石油醚:乙酸乙酯,体积比为1:1,收率55%。
现将根据实施例1~3的制备方法而采用不同的原料制备的该类衍生物列入表1,部分衍生物1H NMR、13C NMR(Bruker AV-500spectrometer using tetramethylsilane asthe internal standard)、熔点数据参见表2。
表1目标化合物I-1的结构
表2部分目标化合物的核磁及熔点数据
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实施例4
利用本发明提供的衍生物进行杀菌活性测试,测试对象为玉米纹枯病菌(Rhizoctoniasolani)、小麦赤霉病菌(Gibberella zeae)、水稻稻瘟病菌(Pyricularia grisea)、黄瓜灰霉病菌(Botrytis cinerea)、苹果炭疽病菌(Colletotrichum gloeosporioides)、苹果轮纹病菌(Physalospora piricola)和链格菌(Alternaria sp.),测试方法为菌病直径抑制法。测试方法如下:
准确称取5.0mg的目标化合物置于1.5mL离心管中,加入2滴二甲基亚砜溶解,然后用0.1%的吐温80水溶液稀释至10mL,得到500μg/mL的待测母液。取1mL待测母液与9mL PDA培养基混合均匀,得到测试浓度为50μg/mL的含药培养基。用直径为7mm的打孔器取相应菌饼置于含药培养基中,25℃条件下培养72小时,根据菌落直径计算化合物的抑菌率,蒸馏水为阴性对照,氟吡菌酰胺和多菌灵为阳性对照,每个处理重复三次,计算平均值和标准偏差。
上述离体杀菌活性的测试结果如表3所示:
表3部分目标化合物I的离体杀菌活性抑制率(%)
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离体杀菌活性结果表明,部分目标化合物显示出了优异的广谱杀菌活性,例如化合物I-4对玉米纹枯病菌、小麦赤霉病菌、水稻稻瘟病菌、黄瓜灰霉病菌以及苹果炭疽病菌均显示出优异的抑菌活性,并且对黄瓜灰霉病菌和苹果炭疽病菌的抑菌活性明显优于商品化药剂多菌灵和氟吡菌酰胺。化合物I-24对测试的七种植物病原菌玉米纹枯病菌、小麦赤霉病菌、水稻稻瘟病菌、黄瓜灰霉病菌、苹果炭疽病菌、苹果轮纹病菌以及链格菌均显示出优异的广谱杀菌活性,抑制率均超过90%。相对于商品化药剂戊唑醇和多菌灵,大多数目标化合物对苹果轮纹病菌表现出较弱的抑菌活性,其中化合物I-24除外,其对苹果轮纹病菌的抑菌率达到93.8%。从构效关系分析,苯环4位取代基为吸电子基时的抑菌活性优于供电子基,尤其以F取代时抑菌活性最佳。例如,化合物I-4、I-14和I-14均表现出优于其他目标化合物的广谱抑菌活性。以上研究结果有助于开发新型酰肼类杀菌剂。
Claims (11)
1.一种式I-1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐,具备如下化学结构式:
;
其中,式I-1中基团X选自硫、氧或NH;
R1选自以下基团:氢或C1-C6直链或支链烷基中任意一种;
R2选自以下基团:氢、C1-C6直链或支链烷基、卤代C1-C6直链或支链烷基中任意一种;
R3选自以下基团:氢或C1-C6直链或支链烷基中任意一种;
R4选自以下基团:氢或卤素中任意一种;
R5,R6选自以下基团:氢或C1-C6直链或支链烷基中任意一种;
R7选自以下基团:氢、卤素、C1-C6直链或支链烷基、卤代C1-C6直链或支链烷基、C1-C6烷氧基中任意一种;
R8选自以下基团:氢或C1-C6直链或支链烷基中任意一种;
R9选自以下基团:氢、卤素或C1-C6直链或支链烷基中任意一种。
2.根据权利要求1所述化合物或其农学上可接受的盐,其特征在于,其中所述卤代C1-C6直链或支链烷基中的氢原子被部分或全部卤原子取代。
3.根据权利要求1-2中任一项所述化合物或其农学上可接受的盐,其特征在于,所述卤素和/或卤代原子为氟、氯、溴或碘中任意一种。
4.根据权利要求1-2任一项所述化合物或其农学上可接受的盐,其特征在于,所述的C1-C6直链或支链烷基选自甲基、乙基、正丙基或异丙基;所述的C1-C6烷氧基选自甲氧基、乙氧基、正丙氧基或异丙氧基,所述的卤代C1-C6直链或支链烷基选自CFH2-、CF2H-、CF3-、CH3CFH-、CH3CF2-或CH3CF2-。
5.一种权利要求1所述的式I-1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐的制备方法,它包括如下步骤:
(1)吡啶化合物1溶解到有机溶剂中,与氯乙酸甲酯反应,制备得到含吡啶的酯类化合物2;其中化合物1和化合物2的化学结构式如下:
;
(2)含吡啶的酯类化合物2溶解到混合溶剂中,经碱水解制备含吡啶的羧酸化合物3;化合物3溶解到有机溶剂中,在缩合剂条件下,与芳香肼类化合物4反应,制备含吡啶的酰肼类化合物I-1;其中,化合物3、化合物4和目标化合物I-1的化学结构式如下:
;
其中,化合物1、化合物2、化合物3、化合物4和式I-1中基团X、R1,R2,R3,R4,R5,R6,R7,R8,R9定义与权利要求1中定义相同。
6.根据权利要求5所述的制备方法,其特征在于,步骤(1)或步骤(2)中的有机溶剂选自N,N-二甲基甲酰胺、乙醇、乙酸乙酯、甲醇、甲苯、DMSO、丙酮、甲基叔丁基醚、乙醚中的一种或多种;步骤(2)中的混合溶剂为N,N-二甲基甲酰胺、乙醇、乙酸乙酯、甲醇、甲苯、DMSO、丙酮、水中的两种或多种。
7.根据权利要求6所述的制备方法,其特征在于,步骤(1)或步骤(2)中的有机溶剂为N,N-二甲基甲酰胺;步骤(2)中的混合溶剂为甲醇和水。
8.根据权利要求5所述的制备方法,其特征在于,步骤(2)中碱选自有机碱或无机碱,无机碱选自钠氢,碳酸钠,碳酸钾,碳酸铯,碳酸氢钠,碳酸氢钾,氢氧化钠,氢氧化钾,氢氧化锂或氢氧化钡一种或两种或多种;有机碱选自N,N-二异丙基乙胺、三乙胺、二异丙基酰胺锂、正-C1-6烷基锂、六甲基二硅氮烷锂、六甲基二硅氮烷钾、六甲基二硅氮烷钠、四甲基哌啶锂、丁氧基钾、戊氧基钾一种或两种或多种。
9.根据权利要求5-8中任一项所述制备方法,所述步骤(2)中的缩合剂选自1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐和4-二甲氨基吡啶。
10.一种农药组合物,其包含至少一种固体或液体载体和权利要求1-4中任一项所述式I-1所示的含吡啶结构的酰肼类化合物或其农学上可接受的盐。
11.如权利要求1-4中任一项所述式I-1所示的含吡啶结构的酰肼类化合物在制备防治玉米纹枯病菌、小麦赤霉病菌、水稻稻瘟病菌、黄瓜灰霉病菌、苹果炭疽病菌、苹果轮纹病菌或链格菌的农用杀菌剂中的用途。
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