CN112625029A - 芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 - Google Patents
芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 Download PDFInfo
- Publication number
- CN112625029A CN112625029A CN202011555258.XA CN202011555258A CN112625029A CN 112625029 A CN112625029 A CN 112625029A CN 202011555258 A CN202011555258 A CN 202011555258A CN 112625029 A CN112625029 A CN 112625029A
- Authority
- CN
- China
- Prior art keywords
- nitrogen
- oxy
- carbon atoms
- arylhydrocarbyl
- pyrazole
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 101100339555 Zymoseptoria tritici HPPD gene Proteins 0.000 title claims abstract 9
- -1 Aryl alkyl nitrogen (oxygen) acetyl pyrazole Chemical compound 0.000 title abstract description 26
- 241000196324 Embryophyta Species 0.000 claims abstract description 49
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 230000002363 herbicidal effect Effects 0.000 claims abstract description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- BHTZCIGVYSJBQB-UHFFFAOYSA-N 1-(1h-pyrazol-5-yl)ethanone Chemical compound CC(=O)C=1C=CNN=1 BHTZCIGVYSJBQB-UHFFFAOYSA-N 0.000 claims description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000009333 weeding Methods 0.000 claims description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 150000001875 compounds Chemical group 0.000 abstract description 16
- 125000003118 aryl group Chemical group 0.000 abstract description 10
- 239000004009 herbicide Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 20
- 102100028626 4-hydroxyphenylpyruvate dioxygenase Human genes 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000002689 soil Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 238000000132 electrospray ionisation Methods 0.000 description 8
- IGMNYECMUMZDDF-UHFFFAOYSA-N homogentisic acid Chemical compound OC(=O)CC1=CC(O)=CC=C1O IGMNYECMUMZDDF-UHFFFAOYSA-N 0.000 description 8
- 238000004949 mass spectrometry Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000005507 spraying Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 240000008042 Zea mays Species 0.000 description 6
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000009331 sowing Methods 0.000 description 6
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 5
- 235000005822 corn Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- KKADPXVIOXHVKN-UHFFFAOYSA-N 4-hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=C(O)C=C1 KKADPXVIOXHVKN-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 244000237956 Amaranthus retroflexus Species 0.000 description 3
- 235000013479 Amaranthus retroflexus Nutrition 0.000 description 3
- 235000010823 Digitaria sanguinalis Nutrition 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 244000025670 Eleusine indica Species 0.000 description 3
- 235000014716 Eleusine indica Nutrition 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003337 fertilizer Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QPIPRCULMJUJFZ-UHFFFAOYSA-N CN(C=C1)NC1(C1CC1)O Chemical compound CN(C=C1)NC1(C1CC1)O QPIPRCULMJUJFZ-UHFFFAOYSA-N 0.000 description 2
- 241001597062 Channa argus Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 235000001602 Digitaria X umfolozi Nutrition 0.000 description 2
- 235000017898 Digitaria ciliaris Nutrition 0.000 description 2
- 235000005476 Digitaria cruciata Nutrition 0.000 description 2
- 235000006830 Digitaria didactyla Nutrition 0.000 description 2
- 235000005804 Digitaria eriantha ssp. eriantha Nutrition 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 239000005578 Mesotrione Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- FKUYMLZIRPABFK-UHFFFAOYSA-N Plastoquinone 9 Natural products CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCC1=CC(=O)C(C)=C(C)C1=O FKUYMLZIRPABFK-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- KPUREKXXPHOJQT-UHFFFAOYSA-N mesotrione Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1C(=O)CCCC1=O KPUREKXXPHOJQT-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000003895 organic fertilizer Substances 0.000 description 2
- FKUYMLZIRPABFK-IQSNHBBHSA-N plastoquinone-9 Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC1=CC(=O)C(C)=C(C)C1=O FKUYMLZIRPABFK-IQSNHBBHSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
- WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 240000006995 Abutilon theophrasti Species 0.000 description 1
- 241000448435 Acalypha australis Species 0.000 description 1
- 241000981770 Buddleja asiatica Species 0.000 description 1
- 241001164374 Calyx Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 244000067456 Chrysanthemum coronarium Species 0.000 description 1
- 235000007871 Chrysanthemum coronarium Nutrition 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 244000152970 Digitaria sanguinalis Species 0.000 description 1
- 244000239348 Echinochloa crus galli var. praticola Species 0.000 description 1
- 244000058871 Echinochloa crus-galli Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 244000064622 Physalis edulis Species 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 235000001855 Portulaca oleracea Nutrition 0.000 description 1
- 244000234609 Portulaca oleracea Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 244000067505 Xanthium strumarium Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 241001148683 Zostera marina Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005001 aminoaryl group Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 230000000903 blocking 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
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 244000230342 green foxtail Species 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- RIJWDPRXCXJDPK-UHFFFAOYSA-N methyl 3-cyclopropyl-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1CC1 RIJWDPRXCXJDPK-UHFFFAOYSA-N 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000013384 organic framework Substances 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- KXFJZKUFXHWWAJ-UHFFFAOYSA-N p-hydroxybenzoylformic acid Natural products OC(=O)C(=O)C1=CC=C(O)C=C1 KXFJZKUFXHWWAJ-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 210000001916 photosynthetic cell Anatomy 0.000 description 1
- 230000005080 plant death Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000004382 potting Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000003971 tillage Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明公开了芳烃基氮(氧)乙酰吡唑类HPPD抑制剂、制备方法及用途，该抑制剂的结构通式如下。本发明构建了完全不同于现已市场化HPPD抑制剂的化合物骨架结构，用作除草剂，对杂草生长抑制效果显著。
Description
技术领域
本发明涉及HPPD抑制剂及制备方法及用途，特别芳烃基氮(氧)乙酰吡唑类HPPD抑制剂、制备方法及用途。
背景技术
对羟基苯基丙酮酸双氧化酶(4-hydroxyphenylpyruvate dioxygenase，HPPD)存在于各种生物体中，是一种依赖二价铁离子的非血红素氧化酶，在一个单一催化循环中将对羟基丙酮酸经脱羧、取代基迁移和芳香环的氧化催化转化为尿黑酸。在植物体中，HPPD将对羟基苯基丙酮酸催化转化为尿黑酸这一过程时酪氨酸在植物体中代谢过程的一部分，催化的产物尿黑酸是指物体赖以生存的关键物质质体醌与生育酚生物合成的起始原料；此外，HPPD在酪氨酸降解中起作用，由于它具有异戊烯苯醌的芳基前体，亦即作为保护光合细胞的重要载体的质体醌与生育酚，因而具有重要的组成代谢作用。靶向除草剂抑制HPPD，导致阻碍4-羟苯基丙酮酸向尿黑酸的转变并间接抑制类胡萝卜素的合成，促使植物分生组织产生白化症状，最终导致植物死亡，具有重大农业意义。鉴于其上述重要作用和特点，使其成为继ALS、ACC以及PPO之后又一新的除草剂靶标酶。由于该酶抑制剂用于除草方面具有广谱、高效、残留低、环境相容性好、使用安全的特点，且尚未发现有关其抗性的报道，这更加引起相关研究人员对其抑制剂与构效关系研究的热情，同时开展了相关研究。
发明内容
发明目的：本发明目的是提供芳烃基氮(氧)乙酰吡唑类HPPD抑制剂。
本发明的另一目的是提供所述提供芳烃基氮(氧)乙酰吡唑类HPPD抑制剂的制备方法。
本发明的另一目的是提供除草剂的组合物。
本发明的最后一目的是提供芳烃基氮(氧)乙酰吡唑类HPPD抑制剂在控制有害植物上的用途。
技术方案：本发明提供一种具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂：
其中，
M为氧原子、氮原子；
Het为吡啶、吡嗪、嘧啶、哒嗪、三嗪；
R1为卤素、硝基、三氟甲基、氰基、C1-C6碳原子的烷基砜基、羧基、酯基；
R2为氢原子、C1-C6碳原子的烷基、C1-C6碳原子的烷基氨基、C1-C6碳原子的烷
氧基、取代苯基氨基、取代苯氧基；
R3为氢原子、环丙烷基、三氟甲基、C1-C6碳原子的烷基；
R4为氢原子、C1-C6碳原子的烷基。
进一步地，所述卤素为氟、氯、溴。
所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂的制备方法，包括如下步骤：
以取代的二氯杂环为起始原料，与乙醇酸甲酯反应得到C1，C1与取代苯胺在三氟乙酸作用下，得到中间体C2，C2酯解后得到C3，C3与取代的1，3-二甲基-1H-吡唑-5-醇在4-二甲氨基吡啶，1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐作用下，得到中间体C5，中间体C5发生重排，得到终产C6。
一种除草剂的组合物，其含有治疗有效量的一种或多种如权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂及药学上可接受的载体或辅料。
进一步地，所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂在控制有害植物上的用途。
进一步地，所述有害植物为一年生、多年生草本杂草及木本杂草。
所述的组合物在控制有害植物上的用途。
进一步地，所述有害植物为一年生、多年生草本杂草及木本杂草。
一种除草的方法，将除草有效量的权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂使用在植物上或者有害植物区域。
一种除草的方法，将除草有效量的权利要求4组合物使用在植物上或者有害植物区域。
本发明中，“卤素原子”是指氟原子、氯原子、溴原子等。
“C1-6烃基(基团)”是指，C1-6烷基，C2-7烯基，C1-6烷氧基，C2-6烯氧基，C1-6烷基-羰基单或二取代的氨基芳基，等等。
“C1-6烷基(基团)”是指，例如、甲基、乙基、异丙基、丁基、仲丁基、戊基、异戊基、1-乙基丙基、1-甲基丁基、异己基、1，1-二甲基丁基、3，3-二甲基丁基、2-乙基丁基、1-乙基-2-甲基丙基、1，2-二甲丙基，等等。
“C1-6烷氧基(基团)”是指，例如，甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、异丁氧基、仲丁氧基、叔丁氧基、戊氧基、异戊氧基、新戊氧基、己氧基，等等。
当化合物(I)是盐形式时，包括：金属盐、铵盐、与有机碱形成的盐、与无机酸形成的盐、与有机酸形成的盐、与碱性或酸性氨基酸形成的盐，等等。金属盐的优选例子包括：碱金属盐，例如钠盐、钾盐等等；碱土金属盐，例如钙盐、镁盐、钡盐等等；招盐，等等。与有机碱形成的盐的优选例子包括与下列有机碱形成的盐：三甲胺、三乙胺、吡啶、甲基吡啶、2，6-二甲基吡啶、乙醇胺、二乙醇胺、三乙醇胺、环己胺、二环己基胺、N，N’-二苄基乙二胺，等等。
有益效果：本发明区别于传统HPPD抑制剂苯环体系，构建了完全不同于市场化HPPD抑制剂的有机骨架，并且除草活性与硝磺草酮相当。用作除草剂时，生长抑制效果显著。
具体实施方式
以下实施例中，“室温”通常是指大约10℃至大约35℃。混合溶剂表示的比例是体积混合比例，除非另作说明。
利用Fourier变换类型NMR，测定1H-NMR(质子核磁共振波谱)。对于分析，使用ACD/SpecManager等。不描述很轻的质子(例如羟基、氨基等等)的峰。
利用LC/MS(液相色谱质谱仪)测定MS(质谱)。作为电离法，使用ESI(电喷射离子化)方法等。数据表示那些实测值。通常，观察分子离子峰。在盐的情况下，通常观察到游离形式的分子离子峰或碎片离子峰。
实施例1
中间体通式C1制备通法：
具体实施例：2-((2-氯-5-氟嘧啶-4-基)氧基)乙酸甲酯的制备
将2，4-二氯-5氟嘧啶(1.66g)，碳酸钾(1.40g)，乙醇酸甲酯(1.0g)和20mL乙腈，于100mL三口反应瓶中回流反应4h。TLC中控反应完全后，抽滤除去固体盐，滤液脱溶，重结晶，减压干燥至恒重，得2-((2-氯-5-氟嘧啶-4-基)氧基)乙酸甲酯(1.75g)。
1H NMR(300MHz，CDCl3)δ8.28(d，J＝2.1Hz，1H)，5.06(s，2H)，3.83(s，3H).MS(ESI+)：[M+H]+221.0。
实施例2
中间体C2制备通法：
具体实施例：2-((5-氟-2-(苯氨基)嘧啶-4-基)氧基)乙酸甲酯的制备
将实施例1中所得2-((2-氯-5-氟嘧啶-4-基)氧基)乙酸甲酯(1.1g)，苯胺(0.51g)，三氟乙酸(0.57g)，正丁醇15mL，于100mL三口反应瓶中在80℃下反应5h。TLC监控反应进程，待反应完全后，反应液冷却至室温。有白色固体析出，抽滤，石油醚洗涤，减压干燥至恒重，得2-((5-氟-2-(苯氨基)嘧啶-4-基)氧基)乙酸甲酯(0.70g)。
1H NMR(300MHz，CDCl3)δ8.09(d，J＝2.7Hz，1H)，7.46(d，J＝8.2Hz，2H)，7.31(t，J＝7.9Hz，2H)，7.26(s，1H)，7.05(t，J＝7.3Hz，1H)，4.96(s，2H)，3.77(s，3H).MS(ESI+)：[M+H]+278.1。
实施例3
中间体通式C3制备通法：
具体实施例：2-((5-氟-2-(苯氨基)嘧啶-4-基)氧基)乙酸的制备
将实施例2中所得2-苯胺-5-氟嘧啶-4-氧乙酸甲酯(1.10g)，碳酸钾(0.83g)，20mL水于100mL单口瓶中回流反应6h。取样酸化，EA萃取，TLC中控。待反应完全后，冰浴条件下加入3N HCl酸化体系pH至1，析出白色固体，抽滤，减压干燥除水至恒重，得2-((5-氟-2-(苯氨基)嘧啶-4-基)氧基)乙酸(0.93g)。
1H NMR(300MHz，DMSO)δ13.20(s，1H)，9.56(s，1H)，8.34(d，J＝2.8Hz，1H)，7.62(d，J＝8.0Hz，2H)，7.25(t，J＝7.7Hz，2H)，6.94(t，J＝7.2Hz，1H)，4.98(s，2H).MS(ESI+)：[M+H]+264.1。
实施例4
中间体通式C4制备通法：
具体实施例：3-环丙基-1-甲基吡唑醇的制备
向100mL三口反应瓶中加入3-环丙基-3-氧代丙酸甲酯(13.00g)和50mL乙醇冷肼降温至-10℃，缓慢滴加40％甲基肼水溶液(11.50g)，保持体系温度不高于-5℃。滴加完毕后，常温搅拌2h，油浴升温至回流反应3h。脱溶，得米黄色固体(15.4g)。30mL EA重结晶，得白色固体(13.2g)。
1H NMR(300MHz，CDCl3)δ10.30(s，1H)，6.38(m，1H)，2.68-2.25(m，1H)，1.02-1.00(m，2H)，0.91-0.89(m，2H).MS(ESI+)：[M+H]+139.1。
实施例5
中间体通式C5制备通法：
具体实施例：3-环丙基-1-甲基-1H-吡唑-5-基-2-((5-氟-2-(苯基氨基)嘧啶-4-基)氧基)乙酸酯的制备
将实施例3中所得2-((5-氟-2-(苯氨基)嘧啶-4-基)氧基)乙酸(0.68g)，3-环丙基-1-甲基吡唑醇(0.39g)，4-二甲氨基吡啶(DMAP 0.05g)，1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐(EDCI 0.59g)和20mL无水二氯甲烷加入100mL单口瓶中，开启氮气保护系统，常温反应，TLC中控直至反应完全。产物脱溶，经硅胶柱色谱分离纯化得上述化合物(0.50g)。
1H NMR(300MHz，CDCl3)δ8.16(d，J＝2.6Hz，1H)，7.43(d，J＝7.7Hz，2H)，7.27(d，J＝4.5Hz，2H)，7.18-7.17(m，1H)，7.06(t，J＝7.4Hz，1H)，5.92(s，1H)，5.19(s，2H)，3.53(s，2H)，2.04-1.81(m，1H)，0.99-0.85(m，2H)，0.86-0.62(m，2H).MS(ESI+)：[M+H]+384.1。
实施例6
C6(化合物2)制备通法：
具体实施例：(化合物2)的制备
将实施例5中所得3-环丙基-1-甲基-1H-吡唑-5-基-2-((5-氟-2-(苯基氨基)嘧啶-4-基)氧基)乙酸酯(0.50g)，无水三乙胺(0.40g)，丙酮氰醇(0.05g)和20mL无水二氯甲烷在氮气保护的条件下于室温搅拌反应12h。反应液脱溶，加入30mL水超声溶解产物的三乙胺盐。冰浴条件下加入3N HCl酸化体系pH至1，析出白色固体，抽滤，减压干燥除水至恒重，得化合物2(0.35g)。
1H NMR(300MHz，DMSO-d6)δ9.54(s，1H)，8.36(d，J＝3.1Hz，1H)，7.55(d，J＝8.0Hz，2H)，7.02(d，J＝7.7Hz，2H)，6.88(t，J＝7.2Hz，1H)，5.57(s，2H)，3.43(s，3H)，2.55(s，0H)，0.95(s，2H)，0.89-0.77(m，2H).MS(ESI+)：[M+H]+384.1。
实施例7
化合物3-21的制备方法与化合物1、2的区别主要在于：苯胺基团不同、吡唑醇取代基不同，见表1。
表1.典型化合物结构式及核磁图谱数据
除草活性测试实验实施例
一、实验步骤：
温室盆栽除草活性测试：
样品配置：用分析天平(0.0001g)称取原药，用含1％吐温-80乳化剂的DMF溶解配制成1.0％母液，然后用蒸馏水稀释备用。
实验方法：活性普筛(盆栽法，苗后茎叶喷雾处理)：供试靶标为苘麻、鳢肠、反枝苋、稗草、狗尾、马唐。取直径6cm花盆，装复合土基(V菜园土：V育苗基质＝1/2)至3/4处，将待测杂草(茼麻、鳢肠、反枝苋、稗草、马唐和狗尾草种子均匀的播入花盆中，直接播种上述六种杂草靶标出芽率≥85％)，覆土0.2cm，底部加水方式使土壤吸水饱和后置于温室内培养生长，土壤含水量保持适宜，待杂草长至3叶期左右备用。待杂草生长至4叶期左右时，在自动喷雾装置上进行芽后茎叶喷雾处理。每个处理重复2-3次并设空白对照。处理后静置4-5小时，杂草叶片上药液吸收后，移入温室内培养。每天定时观察杂草生长情况定期记录受害症状，施药后15天左右目测调查化合物的除草活性并计算抑制率。
二、作物安全性测试：
取内径12cm花盆，装复合土基(V菜园土：V育苗基质＝1/2)至3/4处将待测作物(小麦、玉米、水稻、大豆、棉花、油菜)种子均匀的播入花盆中，覆土0.2cm，于恒温温室中培养。待植株长至4-5叶左右时，各化合物按照150g ai/ha剂量在自动喷雾塔施药后，待杂草叶面药液吸收后移入温室培养，15天后测其鲜重抑制率，以喷施无菌水为空白对照。
田间除草活性测试：
田间测试时主要针对的作物是玉米，品种为郑单958。试验地以阔叶杂草为优势种，主要阔叶杂草为反枝苋、马齿苋、铁苋菜、黎、打碗花及少量苍耳等；主要禾本科杂草为马唐和牛筋草。基本代表北方一年两熟地区夏玉米田杂草的种类及群落组成。
实验田地旋耕后机械条播夏玉米，密度5000株/亩。播种前施有机肥，并随机器播种时施入复合肥50Kg/亩。待测化合物制剂配置为乳油，实验中所用的对照药剂为10％硝磺草酮，由先正达(中国)投资有限公司生产。
实验过程时，田间小区采用随机区组设计，田间小区面积为24m2。喷雾器械为新加坡利农背负式喷雾器，扇形喷头。施药时间在玉米4-5叶期，阔叶杂草3-5叶期，禾本科杂草4-6叶期进行茎叶喷雾处理，施药一次，喷液量设置为450L/ha。实验的过程中除喷洒待测的化合物外，无其它试剂。
试验地土质为沙壤，需测定土壤有机质含量、碱解氮、有效磷、有效钾和土壤pH值。试验期间采用喷灌浇水2次。播种前撒施有机肥，播种时使用复合肥50Kg为底肥。玉米施药前间苗，每亩留5000株左右，未进行其它田间作业。施药前，每小区对角线定3个0.25m2样点，分草种调查点内杂草基数。施药后5天，目测观察待测化合物的速效性，记录杂草典型的中毒症状；施药后10天目测观察杂草防效，施药后15天，调查样点内残存杂草种类及株数，计算防效。
部分化合物除草活性如下表2(％，生长抑制率)(药后20d)：
表2.部分化合物除草活性测试结果
注：“*”表示有白化现象。
本发明的化合物具有优良的HPPD酶抑制作用，对一年生和多年生草本杂草及木本杂草的生长抑制具有显著的效果。
Claims (10)
1.一种具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂：
其中，
M为氧原子、氮原子；
Het为吡啶、吡嗪、嘧啶、哒嗪、三嗪；
R1为卤素、硝基、三氟甲基、氰基、C1-C6碳原子的烷基砜基、羧基、酯基；
R2为氢原子、C1-C6碳原子的烷基、C1-C6碳原子的烷基氨基、C1-C6碳原子的烷氧基、取代苯基氨基、取代苯氧基；
R3为氢原子、环丙烷基、三氟甲基、C1-C6碳原子的烷基；
R4为氢原子、C1-C6碳原子的烷基。
2.根据权利要求1所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂，其特征在于：所述卤素为氟、氯、溴。
3.权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂的制备方法，其特征在于：包括如下步骤：
其中，R1、R2、R3、R4如权利要求1所述，
以取代的二氯杂环为起始原料，与乙醇酸甲酯反应得到C1，C1与取代苯胺在三氟乙酸作用下，得到中间体C2，C2酯解后得到C3，C3与取代的1，3-二甲基-1H-吡唑-5-醇在4-二甲氨基吡啶，1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐作用下，得到中间体C5，中间体C5发生重排，得到终产C6。
4.一种除草剂的组合物，其含有治疗有效量的一种或多种如权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂及药学上可接受的载体或辅料。
5.权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂在控制有害植物上的用途。
6.根据权利要求5所述的用途，所述有害植物为一年生、多年生草本杂草及木本杂草。
7.权利要求4所述的组合物在控制有害植物上的用途。
8.根据权利要求7所述的用途，所述有害植物为一年生、多年生草本杂草及木本杂草。
9.一种除草的方法，其特征在于：将除草有效量的权利要求1或2所述的具有通式I的芳烃基氮(氧)乙酰吡唑类HPPD抑制剂使用在植物上或者有害植物区域。
10.一种除草的方法，其特征在于：将除草有效量的权利要求4组合物使用在植物上或者有害植物区域。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011555258.XA CN112625029B (zh) | 2020-12-24 | 2020-12-24 | 芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011555258.XA CN112625029B (zh) | 2020-12-24 | 2020-12-24 | 芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112625029A true CN112625029A (zh) | 2021-04-09 |
| CN112625029B CN112625029B (zh) | 2023-01-31 |
Family
ID=75324516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011555258.XA Active CN112625029B (zh) | 2020-12-24 | 2020-12-24 | 芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112625029B (zh) |
-
2020
- 2020-12-24 CN CN202011555258.XA patent/CN112625029B/zh active Active
Non-Patent Citations (1)
| Title |
|---|
| WANG MAN-MAN ETAL: "Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors", 《BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112625029B (zh) | 2023-01-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111961041B (zh) | 硫代三嗪酮异恶唑啉类化合物及其制备方法和应用、原卟啉原氧化酶抑制剂和除草剂 | |
| WO2010137662A1 (ja) | 植物分枝抑制剤並びにその製造方法及び植物分枝抑制組成物 | |
| CS212243B2 (en) | Means for protection of cultural plants | |
| US10842151B2 (en) | Small molecule compound for enhancing plant stress resistance | |
| CN110317185B (zh) | 苯并五元杂环类hppd酶抑制剂或其盐、除草剂组合物、制备方法与用途 | |
| CN106432081B (zh) | 含4-氯-3-乙基-1-甲基吡唑结构的吡唑肟醚化合物的制备方法和应用 | |
| CN110437221B (zh) | 含芳氧基甲基噁二唑单元的吡唑衍生物及其制备方法和应用 | |
| CN112625029B (zh) | 芳烃基氮(氧)乙酰吡唑类hppd抑制剂、制备方法及用途 | |
| CN113480531B (zh) | 含硫代噻唑烷酮的胡椒环类化合物、制备及其应用 | |
| PL237098B1 (pl) | Nowe ciecze jonowe z kationem acetylocholiny i anionem herbicydowym, sposób ich otrzymywania oraz zastosowanie jako herbicydy | |
| CN115160238B (zh) | 一种喹喔啉苯氧乙酸酯类化合物及其制备方法与应用 | |
| CN112679434B (zh) | 芳氧(硫)偕二氟类hppd抑制剂、制备方法及用途 | |
| CN110330458B (zh) | 芳氧乙酸类hppd抑制剂或其盐、除草剂组合物、制备方法与用途 | |
| CN107602494B (zh) | 含四氮唑基团的氰基丙烯酸酯衍生物的制备和应用 | |
| JP4558496B2 (ja) | 水稲病害防除用殺菌性組成物 | |
| CN108569973A (zh) | 一种双氢茉莉酸（二烷基氨基）酯化合物或其盐 | |
| CN111269223B (zh) | 一种异噁唑肟酯类衍生物及其应用 | |
| JP7325429B2 (ja) | 植物の耐塩性向上剤 | |
| CN115215885A (zh) | 一种苯并噻二嗪酮类化合物、制备方法及应用 | |
| CN112939939B (zh) | 2-(4-氯苯基)吡啶类化合物及其在农药中的应用 | |
| NO167587B (no) | Kontinuerlig fremgangsmaate med hoey gjennomsnittshastighetfor hydrolyse av karbohydrater til etanol under anvendelse av immobiliserte mikroorganismer og enzymer. | |
| CN112979620B (zh) | 6-甲氧基吡啶衍生物及其在农药中的应用 | |
| CN114805197B (zh) | 一种含氟吡啶酰基脲类杀虫杀螨剂 | |
| CN112028894B (zh) | 含三氟甲基吡啶联芳氧基单元的磺酰胺化合物的制备与用途 | |
| CN112939938B (zh) | 2,4,6-三取代吡啶类化合物及其在农药中的用途 |
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 |