WO2022262814A1 - 含肟醚片段的三唑磺酰胺类衍生物及其制备方法和应用和一种杀菌剂及其应用 - Google Patents
含肟醚片段的三唑磺酰胺类衍生物及其制备方法和应用和一种杀菌剂及其应用 Download PDFInfo
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- WO2022262814A1 WO2022262814A1 PCT/CN2022/099178 CN2022099178W WO2022262814A1 WO 2022262814 A1 WO2022262814 A1 WO 2022262814A1 CN 2022099178 W CN2022099178 W CN 2022099178W WO 2022262814 A1 WO2022262814 A1 WO 2022262814A1
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- Prior art keywords
- formula
- oxime ether
- halogen
- alkyl
- application
- Prior art date
Links
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical group ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 title claims abstract description 25
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 150000003852 triazoles Chemical class 0.000 title claims abstract description 11
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 6
- 239000003899 bactericide agent Substances 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 53
- 241000233679 Peronosporaceae Species 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- -1 triazole sulfonamide Chemical class 0.000 claims description 21
- 239000000417 fungicide Substances 0.000 claims description 17
- 229940124530 sulfonamide Drugs 0.000 claims description 17
- 241000196324 Embryophyta Species 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 208000031888 Mycoses Diseases 0.000 claims description 13
- 240000008067 Cucumis sativus Species 0.000 claims description 12
- 230000000855 fungicidal effect Effects 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 102000018832 Cytochromes Human genes 0.000 claims description 7
- 108010052832 Cytochromes Proteins 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 5
- 235000000832 Ayote Nutrition 0.000 claims description 4
- 241000207199 Citrus Species 0.000 claims description 4
- 240000004244 Cucurbita moschata Species 0.000 claims description 4
- 235000009854 Cucurbita moschata Nutrition 0.000 claims description 4
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 claims description 4
- 244000068988 Glycine max Species 0.000 claims description 4
- 235000010469 Glycine max Nutrition 0.000 claims description 4
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims description 4
- 240000003768 Solanum lycopersicum Species 0.000 claims description 4
- 244000061458 Solanum melongena Species 0.000 claims description 4
- 235000002597 Solanum melongena Nutrition 0.000 claims description 4
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 4
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 4
- 240000006365 Vitis vinifera Species 0.000 claims description 4
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 4
- 235000020971 citrus fruits Nutrition 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 235000015136 pumpkin Nutrition 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 241000233622 Phytophthora infestans Species 0.000 claims description 3
- 208000010801 foot rot Diseases 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000004495 emulsifiable concentrate Substances 0.000 claims description 2
- 239000004497 emulsifiable granule Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 12
- 238000012360 testing method Methods 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000575 pesticide Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000027756 respiratory electron transport chain Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000005754 Cyazofamid Substances 0.000 description 3
- 102000015782 Electron Transport Complex III Human genes 0.000 description 3
- 108010024882 Electron Transport Complex III Proteins 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- 239000005802 Mancozeb Substances 0.000 description 3
- 239000005807 Metalaxyl Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- YXKMMRDKEKCERS-UHFFFAOYSA-N cyazofamid Chemical compound CN(C)S(=O)(=O)N1C(C#N)=NC(Cl)=C1C1=CC=C(C)C=C1 YXKMMRDKEKCERS-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
- ZQEIXNIJLIKNTD-UHFFFAOYSA-N methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alaninate Chemical compound COCC(=O)N(C(C)C(=O)OC)C1=C(C)C=CC=C1C ZQEIXNIJLIKNTD-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- XERJKGMBORTKEO-VZUCSPMQSA-N (1e)-2-(ethylcarbamoylamino)-n-methoxy-2-oxoethanimidoyl cyanide Chemical compound CCNC(=O)NC(=O)C(\C#N)=N\OC XERJKGMBORTKEO-VZUCSPMQSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005727 Amisulbrom Substances 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 240000002791 Brassica napus Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- 235000004936 Bromus mango Nutrition 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 244000241235 Citrullus lanatus Species 0.000 description 1
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 235000009849 Cucumis sativus Nutrition 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 239000005756 Cymoxanil Substances 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 241000220225 Malus Species 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 240000007228 Mangifera indica Species 0.000 description 1
- 235000014826 Mangifera indica Nutrition 0.000 description 1
- 241000233654 Oomycetes Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 231100000674 Phytotoxicity Toxicity 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000009184 Spondias indica Nutrition 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- BREATYVWRHIPIY-UHFFFAOYSA-N amisulbrom Chemical compound CN(C)S(=O)(=O)N1C=NC(S(=O)(=O)N2C3=CC(F)=CC=C3C(Br)=C2C)=N1 BREATYVWRHIPIY-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\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)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125507 complex inhibitor Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- QGTOTYJSCYHYFK-RBODFLQRSA-N fenpicoxamid Chemical compound COC1=CC=NC(C(=O)N[C@@H]2C(O[C@@H](C)[C@H](OC(=O)C(C)C)[C@@H](CC=3C=CC=CC=3)C(=O)OC2)=O)=C1OCOC(=O)C(C)C QGTOTYJSCYHYFK-RBODFLQRSA-N 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 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 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000004016 soil organic matter Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
Definitions
- the present invention relates to the field of pesticides, in particular to a triazole sulfonamide derivative containing an oxime ether segment and a preparation method thereof, and a triazole sulfonamide derivative containing an oxime ether segment as a cytochrome bc 1 complex Q i site inhibitor and its application in anti-plant fungal disease, a fungicide and its application in anti-plant fungal disease.
- Complex III (also called cytochrome bc 1 complex), as one of the most promising targets of agricultural fungicides, is to catalyze the electron transfer process from coenzyme Q to cytochrome C, and at the same time transfer protons from the mitochondrial matrix pump to the membrane space.
- the cytochrome bc 1 complex inhibitor acts on the complex III in the respiratory electron transport chain of the mitochondrial respiratory electron transport chain of pathogenic bacteria, interferes with the respiratory electron transport chain to inhibit mitochondrial function, prevents it from producing energy, inhibits the growth of pathogenic bacteria, and eventually leads to its death.
- the target can be divided into Q o site and Q i site. There are as many as 21 kinds of commercial Q o site fungicides based on this target, but with the extension of use time, these fungicides The resistance problem is becoming more and more serious.
- the object of the present invention is to provide a new triazole sulfonamide derivative, in the hope that the triazole sulfonamide derivative can achieve significantly higher antifungal disease control effect at a low concentration.
- the first aspect of the present invention provides a triazole sulfonamide derivative containing an oxime ether segment, the derivative has a structure shown in formula (I):
- R 1 is selected from H, C 3-12 cycloalkyl
- R 2 is selected from H, C 1-12 alkyl
- R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, C substituted by at least one halogen 1-8 alkyl, C 1-8 alkoxy substituted by at least one halogen.
- the second aspect of the present invention provides a method for preparing the triazole sulfonamide derivatives containing oxime ether moiety described in the first aspect, the method comprises the compound represented by formula (II) and the compound represented by formula (III) The compound undergoes a contact reaction;
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are correspondingly the same as those described in the first aspect.
- the third aspect of the present invention provides the use of the aforementioned triazole sulfonamide derivatives containing oxime ether fragments as inhibitors of the Q i site of the cytochrome bc 1 complex.
- the fourth aspect of the present invention provides the application of the above-mentioned triazole sulfonamide derivatives containing oxime ether fragments in resisting plant fungal diseases.
- the fifth aspect of the present invention provides a fungicide, the active ingredient of which is at least one of the above-mentioned triazole sulfonamide derivatives containing a strene segment, based on the total weight of the fungicide, the The content of the active ingredient is 0.1-100% by weight.
- the sixth aspect of the present invention provides an application of the fungicide described in the fifth aspect in the fight against plant fungal diseases.
- the compound provided by the invention has the advantages of high safety and good persistence, and has good fungicidal activity against plant diseases such as downy mildew, downy mildew, blight, and late blight at a relatively low concentration, and has a significantly higher
- technologies such as the existing drugs cyanazimazole, indazole sulfasulfame, metalaxyl, metalaxyl mancozeb, mancozeb, metalaxyl mancozeb, cymoxanil, phytamezamide, etc.
- cucumber downy mildew, soybean blight, tomato late blight, potato late blight, eggplant downy mildew, citrus foot rot, pumpkin blight, grape downy mildew, etc. have potential commercial value.
- the intermediate raw materials involved in the method of the invention are cheap and easy to obtain, and the reaction steps and post-treatment are simple.
- C 1-12 alkyl means an alkyl group with a total of 1-12 carbon atoms, including straight chain alkyl and branched chain alkyl, for example, the total number of carbon atoms can be 1, 2, 3, 4, 5, 6 , 7, 8, 9, 10, 11, 12 straight-chain alkyl, branched-chain alkyl, such as n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, etc.;
- the definition of "C 1-8 alkyl", “C 1-6 alkyl", “C 1-3 alkyl” is similar to the definition of "C 1-12 alkyl", the difference is that the carbon atom Totals vary.
- C 1-8 alkoxy is similar to the definition of "C 1-12 alkyl", the difference is that "C 1-8 alkoxy” is directly connected to the parent nucleus through the O atom, and the carbon
- the total number of atoms is different, indicating an alkoxy group with a total number of carbon atoms of 1-8, including straight-chain alkoxy groups and branched-chain alkoxy groups, for example, the total number of carbon atoms can be 1, 2, 3, 4, 5, 6, or 7 , 8 straight-chain alkoxy, branched-chain alkoxy, for example, can be methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyl yloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, n-hexyloxy.
- the definition of "C 1-3 alkoxy” is similar to the definition of "C 1-8 alkoxy", except that
- C 1-8 alkyl substituted by at least one halogen is similar to the definition of “C 1-8 alkyl ", the difference is that in "C 1-8 alkyl substituted by at least one halogen" At least one H on the alkyl group of is substituted by at least one halogen atom selected from fluorine, chlorine, bromine, iodine, for example, there may be 1, 2, 3, 4, 5, 6, 7 or 8 Hs selected from fluorine , chlorine, bromine, and iodine are substituted by at least one halogen atom, and the total number of carbon atoms in the "C 1-8 alkyl substituted by at least one halogen” is 1-8, for example, trifluoromethyl , difluoromethyl, monofluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, etc.
- C 1-3 alkyl substituted by at least one halogen is similar to the definition of "C 1-8 alkyl substituted by at least one halogen", except that the total number of carbon atoms and/or the number of halogen substituents The number is different.
- C 1-8 alkoxy substituted by at least one halogen is similar to the definition of "C 1-8 alkoxy ", except that "C 1-8 alkoxy substituted by at least one halogen Base” means that at least one H on "C 1-8 alkoxy” is substituted by at least one halogen atom selected from fluorine, chlorine, bromine, and iodine, for example, 1, 2, 3, 4, 5, 6 , 7 or 8 H are replaced by at least one halogen atom selected from fluorine, chlorine, bromine, and iodine, and the total number of carbon atoms in the "C 1-8 alkoxy group substituted by at least one halogen” is 1-8 .
- "C 1-3 alkoxy substituted by at least one halogen” is defined similarly to "C 1-8 alkoxy substituted by at least one halogen", except that the total number of carbon atoms and/or the halogen substituent The number of is different.
- C 3-12 cycloalkyl means a cycloalkyl group with a total of 3-12 carbon atoms, and the ring atoms are all C atoms, for example, the total number of carbon atoms can be 3, 4, 5, 6, 7, 8 .
- C 3-6 cycloalkyl is similar to that of "C 3-12 cycloalkyl", except that the total number of carbon atoms is different.
- the first aspect of the present invention provides a triazole sulfonamide derivative containing an oxime ether segment, the derivative has a structure shown in formula (I):
- R 1 is selected from H, C 3-12 cycloalkyl
- R 2 is selected from H, C 1-12 alkyl
- R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, C substituted by at least one halogen 1-8 alkyl, C 1-8 alkoxy substituted by at least one halogen.
- R 1 is selected from H, C 3-6 cycloalkyl
- R 2 is selected from H, C 1-6 alkyl
- R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halogen, C 1-6 alkyl, C 1-3 alkoxy, cyano, C substituted by at least one halogen 1-3 alkyl, C 1-3 alkoxy substituted by at least one halogen.
- R is selected from H, cyclopropyl
- R 2 is selected from methyl, isopropyl
- R 3 , R 4 , and R 5 are each independently selected from H, F, Cl, methyl, ethyl, isopropyl, tert-butyl, methoxy, -CF 3 , -OCF 3 , and cyano;
- R 6 and R 7 are each independently selected from H, methyl, F, and Cl.
- the triazole sulfonamide derivative containing an oxime ether segment is any one of the compounds in the following Table 1:
- the stereostructure of the compound shown in the formula (I) is not particularly limited in the present invention, the compound shown in the formula (I) can be different stereoisomers or optical isomers or tautomeric
- the present invention includes all stereoisomers or optical isomers or tautomers and mixtures thereof in various ratios.
- Any asymmetric atom (for example, carbon, etc.) of the compounds disclosed in the present invention may exist in a racemic or enantiomerically enriched form, such as a cis-trans configuration (or Z configuration, E configuration).
- the present invention has no special limitation on the method for preparing the triazole sulfonamide derivatives containing oxime ether fragments, and those skilled in the art can prepare them through the characteristics of the structural formula in combination with known methods in the field of organic synthesis.
- the present invention provides the method described in the second aspect below to prepare the triazole sulfonamide derivatives containing the oxime ether segment.
- the second aspect of the present invention provides a method for preparing the triazole sulfonamide derivatives containing an oxime ether moiety described in the first aspect, the method comprising formula (II) The compound and the compound shown in formula (III) carry out contact reaction;
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are correspondingly the same as those described in the first aspect.
- the contact reaction at least meets the following conditions: the temperature is 5-45° C., and the time is 20-60 min.
- the molar ratio of the compound represented by the formula (II) to the compound represented by the formula (III) is (0.5-3):1.
- the method described in the present invention may also include the step of purifying the obtained product.
- the method of purification There is no special requirement for the method of purification, and various purification methods routinely used by those skilled in the art can be adopted, such as , can be extracted with an extractant, dried with a desiccant, and removed by column chromatography and other methods.
- the method for preparing the compound shown in the formula (II) and the compound shown in the formula (III) is not particularly limited in the present invention, and those skilled in the art can combine the known knowledge in the field of organic synthesis with the characteristics of the structural formula method to obtain.
- the third aspect of the present invention provides the use of the aforementioned triazole sulfonamide derivatives containing oxime ether fragments as inhibitors of the Q i site of the cytochrome bc 1 complex.
- the fourth aspect of the present invention provides the application of the aforementioned triazole sulfonamide derivatives containing oxime ether moieties in the fight against plant fungal diseases.
- the plants include but not limited to cucumber, soybean, wheat, tomato, potato, eggplant, corn, rice, pumpkin, citrus, grape, rapeseed, cotton, apple, peach, peanut, watermelon, mango.
- the plant fungal diseases include but are not limited to downy mildew, downy mildew, blight, and late blight.
- the plant fungal diseases include but not limited to cucumber downy mildew, soybean blight, tomato late blight, potato late blight, eggplant downy mildew, citrus foot rot, pumpkin blight, and grape downy mildew.
- the fifth aspect of the present invention provides a fungicide, the active ingredient of which is at least one of the aforementioned triazole sulfonamide derivatives containing oxime ether fragments, and the fungicide’s Based on the total weight, the content of the active ingredient is 0.01-100% by weight.
- the content of the active ingredient is 0.1-99.9% by weight.
- the content of the active ingredient is 1-99.9% by weight.
- the content of the active ingredient is 1% by weight, 2% by weight, 5% by weight, 10% by weight, 15% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight , 45% by weight, 50% by weight, 55% by weight, 60% by weight, 65% by weight, 70% by weight, 75% by weight, 80% by weight, 85% by weight, 90% by weight, 95% by weight.
- the dosage form of the bactericide is selected from the group consisting of hydration, powder, emulsion, suspension, emulsifiable concentrate and granule.
- the sixth aspect of the present invention provides the use of the fungicide described in the fifth aspect in the fight against plant fungal diseases.
- room temperature or normal temperature described below means 25 ⁇ 1°C.
- Step a Add 10mmol of the compound shown in formula 1-1 to a 100mL pear-shaped bottle, add 20mL of ethyl acetate to dissolve, then add copper bromide (12mmol), and reflux for 30min. After TLC monitors that the reaction is complete, use diatomaceous earth to extract Filter, wash twice with ethyl acetate to obtain the filtrate, and spin out the solvent under reduced pressure to obtain the compound shown in formula 1-2.
- Step b Add 8mmol of the compound shown in formula 1-2 to a 100mL pear-shaped bottle, add 20mL of methanol to dissolve, then add methoxyamine hydrochloride (12mmol), react at room temperature for 30min, after TLC monitors that the reaction is complete, ethyl acetate After extraction and drying over anhydrous sodium sulfate, the solvent was spinned out under reduced pressure to obtain the compound represented by formula 1-3.
- Step c Add 6 mmol of the compound shown in formula 1-3 to a 100 mL pear-shaped bottle, add 10 mL of acetonitrile to dissolve, then add anhydrous potassium carbonate (18 mmol), and finally add cyclopropylamine (12 mmol), react at room temperature for 30 min, and monitor by TLC After the reaction is complete, spin out the solvent under reduced pressure, and perform column chromatography to obtain the compound represented by formula (II-1).
- Step a Dissolve 5.05 g of the compound represented by formula 2-1 in 25.0 mL redistilled CH 2 Cl 2 , continue to add 3.95 g redistilled pyridine, and add dropwise 4.4 g redistilled benzene Sulfonyl chloride, after 1 hour of dropwise addition, remove the ice bath, react at room temperature for 16 hours, then distill off CH 2 Cl 2 , then add 25 mL of ethanol, react for 1 hour, filter to obtain a solid, and then use 10 mL of water and Wash with 10 mL of ethanol and dry in vacuum (65°C) to obtain the compound shown in Formula 2-2.
- Step b Dissolve 4.68g of the compound represented by formula 2-2 in 50mL redistilled DMF, mix with 7.8g of anhydrous potassium carbonate solution and stir for 1 hour, then add 7.0g of N,N-dimethyl Sulfonyl chloride, after the reaction is complete, add water and CH 2 Cl 2 successively to extract, dedry to obtain a colorless oil, add a small amount of methanol, a large amount of white solid is precipitated, filter and dry to obtain the compound shown in formula 2-3 compound.
- Step c Dissolve 829mg of the compound represented by formula 2-3 in 10mL of 1,2-dichloroethane, add 20mL of water, add 10mL of acetic acid under ice-cooling, then continuously inject chlorine gas for 20min, and detect the reaction by TLC After completion, extract with CH 2 Cl 2 , dry over anhydrous sodium sulfate, and spin out the solvent to obtain the compound represented by formula (III).
- Preparation 1-4 is the preparation method of the exemplary compound of the general formula of the present invention.
- the specific target compound of the present invention can be prepared according to the similar method of Preparation 1-4 by adjusting the raw materials and process conditions according to the characteristics of the structural formula.
- the specific test method is:
- the experiment adopted the seedling pot method.
- Grade 0 No disease
- Grade 1 Lesion area accounts for less than 5% of the entire leaf area
- Grade 3 Lesion area accounts for 6% to 10% of the entire leaf area
- Grade 5 Lesion area accounts for the entire leaf area 11% to 25% of the area
- Grade 7 the lesion area accounts for 26% to 50% of the entire leaf area
- Grade 9 the lesion area accounts for more than 50% of the entire leaf area.
- disease index before application in CK 0 blank control area disease index after application in CK 1 blank control area
- disease index before application in PT 0 drug treatment area disease index after application in PT 1 drug treatment area.
- the test was arranged to be carried out in Jianye District, Ningbo City, Zhejiang City (from May 2021 to June 2021, the pesticide was applied every 10 days, and the pesticide was applied twice in total).
- the test site (clay loam, pH value 6.85, high fertility level and soil organic matter content) cucumbers were cultivated in the open field.
- the cucumber variety was Baoyang No. 5.
- the soil type, cultivation conditions and water and fertilizer management of each test plot were uniform. Use a sprayer to evenly spray the prepared medicinal liquids of the test agents on the cucumber stems and leaves.
- the compound provided by the present invention has better control effect on plant fungal diseases such as cucumber downy mildew than the prior art (such as the existing drug Cyazofamida, etc.), and has high safety and good durability.
- plant fungal diseases such as cucumber downy mildew
- prior art such as the existing drug Cyazofamida, etc.
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Abstract
一种含肟醚片段的三唑磺酰胺类衍生物及其制备方法和应用和一种杀菌剂及其应用，该衍生物具有式(I)所示的结构。所述化合物在相对较低浓度下针对霜霉病、霜疫霉病、疫病、晚疫病等植物病害具有明显比现有技术更好的防效。
Description
相关申请的交叉引用
本申请要求2021年06月16日提交的中国专利申请202110664809.4的权益，该申请的内容通过引用被合并于本文。
本发明涉及农药领域，具体地，涉及一种含肟醚片段的三唑磺酰胺类衍生物及其制备方法，一种含肟醚片段的三唑磺酰胺类衍生物作为细胞色素bc
1复合物Q
i位点抑制剂以及在抗植物真菌病中的应用，一种杀菌剂及其在抗植物真菌病中的应用。
复合物Ⅲ(也叫细胞色素bc
1复合物)作为当前最具发展前景的农用杀菌剂靶标之一，其作用是催化从辅酶Q到细胞色素C的电子传递过程，同时将质子由线粒体基质泵至膜间隙。而细胞色素bc
1复合物抑制剂是通过作用于病原菌线粒体呼吸电子传递链上的复合体Ⅲ，干扰呼吸电子传递链来抑制线粒体功能，阻止其产生能量，抑制病原菌生长，最终导致其死亡，以达到防治病害的目的。根据复合物Ⅲ的功能该靶标可分为Q
o位点和Q
i位点，基于该靶标的商品化Q
o位点杀菌剂数量多达21种，但随着使用时间的延长，这些杀菌剂的抗性问题越来越严重。
目前商品化的3个Q
i位点杀菌剂(cyazofamid、amisulbrom、fenpicoxamid)，很少有抗性问题的报道，其中，氰霜唑和吲唑磺菌胺对卵菌纲病害有着很好的防效。但由于氰霜唑和吲唑磺菌胺合成复杂，因此成本高昂。
发明内容
本发明的目的是为了提供一种新的三唑磺酰胺类衍生物，以期该类三唑磺酰胺类衍生物能够在低浓度下实现明显更高的抗真菌病防效。
为了实现上述目的，本发明第一方面提供一种含肟醚片段的三唑磺酰胺类衍生物，该衍生物具有式(I)所示的结构：
其中，在式(I)中，
R
1选自H、C
3-12的环烷基；
R
2选自H、C
1-12的烷基；
R
3、R
4、R
5、R
6、R
7各自独立地选自H、卤素、C
1-8的烷基、C
1-8的烷氧基、氰基、由至少一个卤素取代的C
1-8的烷基、由至少一个卤素取代的C
1-8的烷氧基。
本发明第二方面提供一种制备第一方面所述的含肟醚片段的三唑磺酰胺类衍生物的方法，该方法包括将式(II)所示的化合物与式(III)所示的化合物进行接触反应；
其中，在式(II)中，
R
1、R
2、R
3、R
4、R
5、R
6、R
7的定义与第一方面所述的定义对应相同。
本发明的第三方面提供前述含肟醚片段的三唑磺酰胺类衍生物作为细胞色素bc
1复合物Q
i位点抑制剂的应用。
本发明的第四方面提供前述含肟醚片段的三唑磺酰胺类衍生物在抗植物真菌病中的应用。
本发明的第五方面提供一种杀菌剂，该杀菌剂的活性成分为前述含突烯片段的三唑磺酰胺类衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.1-100重量％。
本发明的第六方面提供一种第五方面所述的杀菌剂在抗植物真菌病中的应用。
本发明提供的化合物具有安全性高、持续性好的优点，且在相对较低浓度下针对霜霉病、霜疫霉病、疫病、晚疫病等植物病害具有良好的杀菌活性，具有明显比现有技术(如现有药物氰霜唑、吲唑磺菌胺、甲霜灵、甲霜灵锰锌、代森锰锌、甲霜灵锰锌、霜脲氰、疫霉灵等)更好的防效，如黄瓜霜霉病、大豆疫霉病、番茄晚疫病、马铃薯晚疫病、茄子霜霉病、柑桔脚腐病、南瓜疫病、葡萄霜霉病等，具有潜在的商业化价值。
本发明的方法涉及的中间体原料廉价易得，反应步骤和后处理简单。
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值，这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说，各个范围的端点值之间、各个范围的端点值和单独的点值之间，以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围，这些数值范围应被视为在本文中具体公开。
以下针对本发明的部分基团提供一些示例性的解释，在没有特别说明的情况下，未列举的部分参照如下示例性的解释进行解释。
“C
1-12的烷基”表示碳原子总数为1-12的烷基，包括直链烷基、支链烷基，例如可以为碳原子总数为1、2、3、4、5、6、7、8、9、10、11、12的直链烷基、支链烷基，例如可以为正丁基、异丁基、叔丁基、正戊基、异戊基、正己基等；“C
1-8的烷基”、“C
1-6的烷基”、“C
1-3的烷基”的定义与“C
1-12烷基”的定义相似，不同的是，碳原子总数不同。
“C
1-8的烷氧基”的定义与“C
1-12烷基”的定义相似，不同的是，“C
1-8的烷氧基”通过O原子直接与母核连接，且碳原子总数不同，表示碳原子总数为1-8的烷氧基，包括直链烷氧基、支链烷氧基，例如可以为碳原子总数为1、2、3、4、5、6、7、8直链烷氧基、支链烷氧基，示例性地，可以为甲基氧基、乙基氧基、正丙基氧基、异丙基氧基、正丁基氧基、异丁基氧基、叔丁基氧基、正戊基氧基、异戊基氧基、正己基氧基。“C
1-3的烷氧基”的定义与“C
1-8的烷氧基”的定义相似，不同的是，碳原子总数不同。
“由至少一个卤素取代的C
1-8的烷基”的定义与“C
1-8烷基”的定义相似，不同的是，“由至少一个卤素取代的C
1-8的烷基”中的烷基上的至少一个H由选自氟、氯、溴、碘的至少一种卤素原子取代，例如可以有1、2、3、4、5、6、7或8个H由选自氟、氯、溴、碘的至少一种卤素原子取代，且该“由至少一个卤素取代的C
1-8的烷基”的碳原子总数为1-8，示例性地，可以为三氟甲基、二氟甲基、一氟甲基、一氟乙基、二氟乙基、三氟乙基等。“由 至少一个卤素取代的C
1-3的烷基”与“由至少一个卤素取代的C
1-8的烷基”的定义相似，不同的是，碳原子总数和/或卤素取代基的个数不同。
“由至少一个卤素取代的C
1-8的烷氧基”的定义与“C
1-8烷氧基”的定义相似，不同的是，“由至少一个卤素取代的C
1-8的烷氧基”表示为“C
1-8烷氧基”上的至少一个H由选自氟、氯、溴、碘的至少一种卤素原子取代，例如可以有1、2、3、4、5、6、7或8个H由选自氟、氯、溴、碘的至少一种卤素原子取代，且该“由至少一个卤素取代的C
1-8的烷氧基”的碳原子总数为1-8。“由至少一个卤素取代的C
1-3的烷氧基”与“由至少一个卤素取代的C
1-8的烷氧基”的定义相似，不同的是，碳原子总数和/或卤素取代基的个数不同。
“C
3-12的环烷基”表示碳原子总数为3-12的环烷基，且成环原子均为C原子，例如可以为碳原子总数为3、4、5、6、7、8、9、10、11、12，包括单环、二环、三环等，例如所述二环还包括联二环、螺二环、桥二环、稠二环等，且各个环各自独立地选自三元环、四元环、五元环、六元环、七元环、八元环、九元环、十元环、十一元环或十二元环等，且所述“C
3-12的环烷基”上任意能够被取代的位置能够被取代基取代或未取代，当被取代时，包含取代基在内的整体基团的碳原子总数为3-12。“C
3-6的环烷基”与“C
3-12的环烷基”的定义相似，不同的是，碳原子总数不同。
如前所述，本发明的第一方面提供了一种含肟醚片段的三唑磺酰胺类衍生物，该衍生物具有式(I)所示的结构：
其中，在式(I)中，
R
1选自H、C
3-12的环烷基；
R
2选自H、C
1-12的烷基；
R
3、R
4、R
5、R
6、R
7各自独立地选自H、卤素、C
1-8的烷基、C
1-8的烷氧基、氰基、由至少一个卤素取代的C
1-8的烷基、由至少一个卤素取代的C
1-8的烷氧基。
优选地，在式(I)中，
R
1选自H、C
3-6的环烷基；
R
2选自H、C
1-6的烷基；
R
3、R
4、R
5、R
6、R
7各自独立地选自H、卤素、C
1-6的烷基、C
1-3的烷氧基、氰基、由至少一个卤素取代的C
1-3的烷基、由至少一个卤素取代的C
1-3的烷氧基。
特别优选地，在式(I)中，R
1选自H、环丙基；
R
2选自甲基、异丙基；
R
3、R
4、R
5各自独立地选自H、F、Cl、甲基、乙基、异丙基、叔丁基、甲氧基、-CF
3、-OCF
3、氰基；
R
6、R
7各自独立地选自H、甲基、F、Cl。
根据一种特别优选的具体实施方式，所述含肟醚片段的三唑磺酰胺类衍生物为以下表1中的化合物中的任意一种：
表1
本发明中对所述式(I)所示的化合物的立体结构没有特别限制，所述式(I)所示的化合物可以以不同的立体异构体或光学异构体或互变异构的形式存在，本发明包含所有立体异构体或光学异构体或互变异构及其各种比例的混合物。
本发明公开化合物的任何不对称原子(例如，碳等)均可以以外消旋或对映体富集的形式存在，例如顺反构型(或Z构型，E构型)形式存在。
本发明对制备所述含肟醚片段的三唑磺酰胺类衍生物的方法没有特别的限制，本领域技术人员可以通过结构式的特征，结合有机合成领域内的已知方法制备获得，但是，为了更高收率地获得本发明所述的含肟醚片段的三唑磺酰胺类衍生物，本发明提供如下第二方面所述的方法制备含肟醚片段的三唑磺酰胺类衍生物。
具体地，如前所述，本发明的第二方面提供了一种制备第一方面所述的含肟醚片段的三唑磺酰胺类衍生物的方法，该方法包括将式(II)所示的化合物与式(III)所示的化合物进行接触反应；
其中，在式(II)中，
R
1、R
2、R
3、R
4、R
5、R
6、R
7的定义与第一方面所述的定义对应相同。
优选地，所述接触反应至少满足以下条件：温度为5-45℃，时间为20-60min。
优选地，所述式(II)所示的化合物与式(III)所示的化合物的用量摩尔比为(0.5-3)：1。
本领域技术人员应该理解的是，本发明所述的方法还可以包括对所得产物进行提纯的步骤，对于提纯的方法没有特别的要求，可以采用本领域技术人员常规使用的各种提纯方法，例如，可以采用萃取剂萃取，干燥剂干燥，并通过柱层析等方法除杂。
本发明对制备所述式(II)所示的化合物与所述式(III)所示的化合物的方法没有特别的限制，本领域技术人员可以通过结构式的特征，结合有机合成领域内的已知方法制备获得。
如前所述，本发明的第三方面提供了前述含肟醚片段的三唑磺酰胺类衍生物作为细胞色素bc
1复合物Q
i位点抑制剂的应用。
如前所述，本发明的第四方面提供了前述含肟醚片段的三唑磺酰胺类衍生物在抗植物真菌病中的应用。
优选地，所述植物包括但不限于黄瓜、大豆、小麦、番茄、马铃薯、茄子、玉米、水稻、南瓜、柑桔、葡萄、油菜、棉花、苹果、桃、花生、西瓜、芒果。
特别优选地，所述植物真菌病包括但不限于霜霉病、霜疫霉病、疫病、晚疫病。
优选地，所述植物真菌病包括但不限于黄瓜霜霉病、大豆疫霉病、番茄晚疫病、马铃薯晚疫病、茄子霜霉病、柑桔脚腐病、南瓜疫病、葡萄霜霉病。
如前所述，本发明的第五方面提供了一种杀菌剂，该杀菌剂的活性成分为前述含肟醚片段的三唑磺酰胺类衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.01-100重量％。
优选情况下，所述活性成分的含量为0.1-99.9重量％。
更优选地，所述活性成分的含量为1-99.9重量％。
示例性地，所述活性成分的含量为1重量％、2重量％、5重量％、10重量％、15重量％、20重量％、25重量％、30重量％、35重量％、40重量％、45重量％、50重量％、55重量％、60重量％、65重量％、70重量％、75重量％、80重量％、85重量％、90重量％、95重量％。
优选地，所述杀菌剂的剂型选自水合剂、粉剂、乳剂、悬浮剂、乳油剂和粒剂。
如前所述，本发明的第六方面提供了第五方面所述的杀菌剂在抗植物真菌病中的应用。
以下将通过实例对本发明进行详细描述。以下实例中，在没有特别说明的情况下，使用的各种原料均为市售品。
在没有特别说明的情况下，以下所述的室温或常温均表示25±1℃。
制备例1：
该制备例用来说明式(II-1)所示的化合物的合成：
步骤a：向100mL梨形瓶中加入10mmol式1-1所示的化合物，加入20mL乙酸乙酯溶解，再加入溴化铜(12mmol)，回流30min，TLC监测反应完全后，用硅藻土抽滤，用乙酸乙酯洗2次得到滤液，减压旋出溶剂，即得式1-2所示的化合物。
步骤b：向100mL梨形瓶中加入8mmol式1-2所示的化合物，加入20mL甲醇溶解，再加入甲氧胺盐酸盐(12mmol)，室温反应30min，TLC监测反应完全后，乙酸乙酯萃取，无水硫酸钠干燥后减压旋出溶剂，即得式1-3所示的化合物。
步骤c：向100mL梨形瓶中加入6mmol式1-3所示的化合物，加入10mL乙腈溶解，再加入无水碳酸钾(18mmol)，最后加入环丙胺(12mmol)，室温下反应30min，TLC监测反应完全后，减压旋出溶剂，柱层析即得式(II-1)所示的化合物。
制备例2：
该制备例用来说明式(IV)所示的化合物的合成：
首先，向100mL梨形瓶中加入6mmol式1-3所示的化合物，加入10mL DMF溶解，再加入无水碳酸钾(12mmol)，最后加入邻苯二甲酰亚胺钾(12mmol)，室温下反应30min，TLC监测反应完全后，用硅藻土抽滤，用乙酸乙酯洗2次得到滤液，无水硫酸钠干燥后减压旋出溶剂，柱层析即可得式3-4所示中间体。
然后，向100mL梨形瓶中加入5mmol式3-4所示中间体，加入10m乙醇溶解，再加入水合肼(10mmol)，回流下反应30min，TLC监测反应完全后，用硅藻土抽滤，用甲醇洗2次得到滤液，再用乙酸乙酯萃取，无水硫酸钠干燥后减压旋出溶剂，即可得式(IV)所示的化合物。
制备例3：
该制备例用来说明式(III)所示的化合物的合成：
步骤a：将5.05g式2-1所示的化合物溶于25.0mL重蒸的CH
2Cl
2中，继续加入3.95g重蒸的吡啶，在冰浴的条件下滴加4.4g重蒸的苯磺酰氯，1小时滴加完毕后，移去冰浴，在常温条件下反应16小时，然后蒸去CH
2Cl
2，接着加入25mL乙醇，反应1小时，过滤得固体，然后依次用10mL水和10mL乙醇清洗，真空干燥(65℃)，即得式2-2所示的化合物。
步骤b：将4.68g式2-2所示的化合物溶于50mL重蒸的DMF，与7.8g无水碳酸钾的溶液混合搅拌1小时后，冰浴下加入7.0g的N,N-二甲基磺酰氯，反应完全后，依次加入水、CH
2Cl
2萃取，脱干，得到无色油状物，加入少量甲醇，即析出大量白色固体，抽滤干燥，即得到式2-3所示的化合物。
步骤c：将829mg的式2-3所示结构的化合物溶于10mL的1,2-二氯乙烷中，加入20mL水，冰浴下加入10mL乙酸，然后连续通入氯气20min，TLC检测反应完全后，用CH
2Cl
2萃取，无水硫酸钠干燥，旋出溶剂，即得式(III)所示的化合物。
制备例4：
该制备例用来说明式(I-1)所示的化合物的合成：
向50mL梨形瓶中加入1.1mmol式(II-1)所示的化合物，然后加入10mL超干四氢呋喃溶解，接着加入三乙胺(0.2mL，1.5mmol)，最后加入式(III)所示的化合物(1mmol)，室温反应30min，TLC监测反应完全后，减压旋出溶剂，柱色谱层析即得式(I-1)所示的化合物。
制备例1-4为本发明示例性的通式化合物的制备方法，本发明的具体目标化合物可按照制备例1-4相似的方法，通过结构式的特征适应性的调整原料和工艺条件制备得到。
以下表2中列举前述获得的部分具体化合物的核磁数据：
表2
测试例1
本测试例针对本发明的部分具体化合物进行活性测试，结果见表3。
具体测试方法为：
试验采取幼苗盆栽法。
幼苗盆栽试验的处理，实验化合物剂量见表3。另设不施药剂的空白对照。每个处理重复3次。选用2片真叶平展的黄瓜盆栽幼苗，剪去生长点，用喉头喷雾器进行人工手动喷雾。处理后的试验材料均在药液晾干后，第二天接种黄瓜霜霉病孢子悬浮液，然后放置人工气候室中培养。培养温度：昼25℃。夜间20℃；相对湿度：90％～100％。保湿培养7天后调查防治效果。调查方法按农业部药检所《农药室内生物测定试验准则》-杀菌剂防治黄瓜霜霉病试验盆栽法(NY/T 1156.7-2006)的分级标准分级记载，以病情指数计算防治效果。
0级：无病；1级：病斑面积占整片叶面积的5％以下；3级：病斑面积占整片叶面积的6％～10％；5级：病斑面积占整片叶面积的11％～25％；7级：病斑面积占整片叶面积的26％～50％；9级：病斑面积占整片叶面积的50％以上。
病情指数及防治效果计算方法如下：
式中：CK
0空白对照区施药前病情指数，CK
1空白对照区施药后病情指数，PT
0药剂处理区施药前病情指数，PT
1药剂处理区施药后病情指数。
防效评级列于表3中。
表3中化合物具有与式(I)中化合物相同的母核结构。
表3
80％≦A≦100％；70％≦B<80％，50％≦C<70％，D<50％
测试例2
本测试例针对如下所示的化合物(以下表格中示为活性化合物)进行田间活性测试。
试验安排在浙江省宁波市建邺区进行(2021年5月至2021年6月，每间隔10天施药一次，共施药2次)。试验地(粘壤土，pH值为6.85，肥力水平及土壤有机质含量较高)黄瓜露地栽培，黄瓜品种为宝杨5号，各试验小区的土壤类型、栽培条件及水肥管理等均匀一致。采用喷雾器将配制好的各参试药剂的药液均匀喷施到黄瓜茎叶上。
其余调查和评价方法同测试例1。
本试验期间各药剂处理区内，施药时为霜霉病发生初期，未发生其他药害及其它不良影响。
采用农业部针对农药田间药效试验要求的方法进行试验药剂的处理，调查方法按农业部农药检定所《农药田间药效试验准则(一)》-杀菌剂防治黄瓜霜霉病(GB/T 17980.26-2000)的分级标准分级记载，以病情指数计算防治效果，本测试例的具体测试结果见表4。
表4
80％≦A≦100％；70％≦B<80％，50％≦C<70％，D<50％
由上述测试例可知，本发明提供的化合物针对黄瓜霜霉病等植物真菌病具有比现有技术(如现有药物氰霜唑等)更好的防效，且具有安全性高，持续性好的优势。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。
Claims (10)
- 一种含肟醚片段的三唑磺酰胺类衍生物，其特征在于，该衍生物具有式(I)所示的结构：
其中，在式(I)中，R 1选自H、C 3-12的环烷基；R 2选自H、C 1-12的烷基；R 3、R 4、R 5、R 6、R 7各自独立地选自H、卤素、C 1-8的烷基、C 1-8的烷氧基、氰基、由至少一个卤素取代的C 1-8的烷基、由至少一个卤素取代的C 1-8的烷氧基。 - 根据权利要求1所述的含肟醚片段的三唑磺酰胺类衍生物，其中，在式(I)中，R 1选自H、C 3-6的环烷基；R 2选自H、C 1-6的烷基；R 3、R 4、R 5、R 6、R 7各自独立地选自H、卤素、C 1-6的烷基、C 1-3的烷氧基、氰基、由至少一个卤素取代的C 1-3的烷基、由至少一个卤素取代的C 1-3的烷氧基；优选地，在式(I)中，R 1选自H、环丙基；R 2选自甲基、异丙基；R 3、R 4、R 5各自独立地选自H、F、Cl、甲基、乙基、异丙基、叔丁基、甲氧基、-CF 3、-OCF 3、氰基；R 6、R 7各自独立地选自H、甲基、F、Cl。
- 根据权利要求1或2所述的含肟醚片段的三唑磺酰胺类衍生物，其中，所述含肟醚片段的三唑磺酰胺类衍生物为以下化合物中的任意一种：
- 一种制备权利要求1-3中任意一项所述的含肟醚片段的三唑磺酰胺类衍生物的方法，其特征在于，该方法包括将式(II)所示的化合物与式(III)所示的化合物进行接触反应；
其中，在式(II)中，R 1、R 2、R 3、R 4、R 5、R 6、R 7的定义与权利要求1-3中任意一项所述的定义对应相同；优选地，所述接触反应至少满足以下条件：温度为5-45℃，时间为20-60min；优选地，所述式(II)所示的化合物与式(III)所示的化合物的用量摩尔比为(0.5-3)：1。 - 权利要求1-3中任意一项所述的含肟醚片段的三唑磺酰胺类衍生物作为细胞色素bc 1复合物Q i位点抑制剂的应用。
- 权利要求1-3中任意一项所述的含肟醚片段的三唑磺酰胺类衍生物在抗植物真菌病中的应用；优选地，所述植物真菌病为霜霉病、霜疫霉病、疫病、晚疫病中的至少一种；优选地，所述植物真菌病为黄瓜霜霉病、大豆疫霉病、番茄晚疫病、马铃薯晚疫病、茄子霜霉病、柑桔脚腐病、南瓜疫病、葡萄霜霉病中的至少一种。
- 一种杀菌剂，其特征在于，该杀菌剂的活性成分为权利要求1-3中任意一项所述的含肟醚片段的三唑磺酰胺类衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.01-100重量％；优选地，所述活性成分的含量为0.1-99.9重量％。
- 根据权利要求7所述的杀菌剂，其中，所述活性成分的含量为1-99.9重量％。
- 根据权利要求7或8所述的杀菌剂，其中，所述杀菌剂的剂型选自水合剂、粉剂、乳剂、悬浮剂、乳油剂和粒剂中的至少一种。
- 权利要求7-9中任意一项所述的杀菌剂在抗植物真菌病中的应用。
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| CN115477619A (zh) | 2022-12-16 |
| CN115477619B (zh) | 2024-01-26 |
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