CN118164955A - Novel acaricide and preparation method thereof - Google Patents
Novel acaricide and preparation method thereof Download PDFInfo
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- CN118164955A CN118164955A CN202410283233.0A CN202410283233A CN118164955A CN 118164955 A CN118164955 A CN 118164955A CN 202410283233 A CN202410283233 A CN 202410283233A CN 118164955 A CN118164955 A CN 118164955A
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- 230000000895 acaricidal effect Effects 0.000 title claims abstract description 42
- 239000000642 acaricide Substances 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 29
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 16
- 239000012074 organic phase Substances 0.000 claims description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 14
- 239000005457 ice water Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 2
- OYQVQWIASIXXRT-UHFFFAOYSA-N ethyl 2,4-dioxopentanoate Chemical compound CCOC(=O)C(=O)CC(C)=O OYQVQWIASIXXRT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 13
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 11
- 125000003226 pyrazolyl group Chemical group 0.000 abstract description 9
- 231100000683 possible toxicity Toxicity 0.000 abstract description 6
- 239000002207 metabolite Substances 0.000 abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 3
- 238000011909 oxidative ring-opening Methods 0.000 abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
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- -1 cyanovinyl ester Chemical class 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 10
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 241000238876 Acari Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 5
- XNONCRQWDVQJRP-UHFFFAOYSA-N 7-bromo-4,4-dimethyl-1,3-dihydroquinolin-2-one Chemical compound BrC1=CC=C2C(C)(C)CC(=O)NC2=C1 XNONCRQWDVQJRP-UHFFFAOYSA-N 0.000 description 4
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
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- 239000001257 hydrogen Substances 0.000 description 4
- SWRGSRXQVANORJ-UHFFFAOYSA-N n-(3-bromophenyl)-3-methylbut-2-enamide Chemical compound CC(C)=CC(=O)NC1=CC=CC(Br)=C1 SWRGSRXQVANORJ-UHFFFAOYSA-N 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- APJLTUBHYCOZJI-VZCXRCSSSA-N cyenopyrafen Chemical compound CC1=NN(C)C(\C(OC(=O)C(C)(C)C)=C(/C#N)C=2C=CC(=CC=2)C(C)(C)C)=C1C APJLTUBHYCOZJI-VZCXRCSSSA-N 0.000 description 3
- ZYSGPOXVDOROJU-UHFFFAOYSA-N ethyl 2,5-dimethylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=CC(C)=NN1C ZYSGPOXVDOROJU-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 229940035936 ubiquinone Drugs 0.000 description 3
- 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 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- AWSZRJQNBMEZOI-UHFFFAOYSA-N 2-methoxyethyl 2-(4-tert-butylphenyl)-2-cyano-3-oxo-3-[2-(trifluoromethyl)phenyl]propanoate Chemical compound C=1C=C(C(C)(C)C)C=CC=1C(C#N)(C(=O)OCCOC)C(=O)C1=CC=CC=C1C(F)(F)F AWSZRJQNBMEZOI-UHFFFAOYSA-N 0.000 description 2
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 2
- BDUBTLFQHNYXPC-UHFFFAOYSA-N 3-methylbut-2-enoyl chloride Chemical compound CC(C)=CC(Cl)=O BDUBTLFQHNYXPC-UHFFFAOYSA-N 0.000 description 2
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 2
- 239000005655 Cyflumetofen Substances 0.000 description 2
- JGFBKJBAYISHAG-UHFFFAOYSA-N Ethyl 2,4-dioxohexanoate Chemical compound CCOC(=O)C(=O)CC(=O)CC JGFBKJBAYISHAG-UHFFFAOYSA-N 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
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- 239000012267 brine Substances 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 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 2
- 235000017471 coenzyme Q10 Nutrition 0.000 description 2
- 230000032798 delamination Effects 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
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- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
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- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
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- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 2
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- 229960002167 sodium tartrate Drugs 0.000 description 2
- 235000011004 sodium tartrates Nutrition 0.000 description 2
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- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 2
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- 238000011105 stabilization Methods 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- 239000005660 Abamectin Substances 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- ICMAFTSLXCXHRK-UHFFFAOYSA-N Ethyl pentanoate Chemical compound CCCCC(=O)OCC ICMAFTSLXCXHRK-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NQRFDNJEBWAUBL-UHFFFAOYSA-N N-[cyano(2-thienyl)methyl]-4-ethyl-2-(ethylamino)-1,3-thiazole-5-carboxamide Chemical compound S1C(NCC)=NC(CC)=C1C(=O)NC(C#N)C1=CC=CS1 NQRFDNJEBWAUBL-UHFFFAOYSA-N 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 239000005663 Pyridaben Substances 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
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- 235000020971 citrus fruits Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- NTZFLNAMFHICLK-UHFFFAOYSA-N ethyl 2-ethyl-5-methylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=CC(C)=NN1CC NTZFLNAMFHICLK-UHFFFAOYSA-N 0.000 description 1
- YFONSBZEAHNVCW-UHFFFAOYSA-N ethyl 5-ethyl-1h-pyrazole-3-carboxylate Chemical compound CCOC(=O)C=1C=C(CC)NN=1 YFONSBZEAHNVCW-UHFFFAOYSA-N 0.000 description 1
- LDRIQRYSIQKISI-UHFFFAOYSA-N ethyl 5-ethyl-2-methylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=CC(CC)=NN1C LDRIQRYSIQKISI-UHFFFAOYSA-N 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
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- DYDNPESBYVVLBO-UHFFFAOYSA-N formanilide Chemical compound O=CNC1=CC=CC=C1 DYDNPESBYVVLBO-UHFFFAOYSA-N 0.000 description 1
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- 230000006872 improvement Effects 0.000 description 1
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- ZYHMJXZULPZUED-UHFFFAOYSA-N propargite Chemical compound C1=CC(C(C)(C)C)=CC=C1OC1C(OS(=O)OCC#C)CCCC1 ZYHMJXZULPZUED-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- DZVWKNFPXMUIFA-UHFFFAOYSA-N pyflubumide Chemical compound C1=C(CC(C)C)C(C(OC)(C(F)(F)F)C(F)(F)F)=CC=C1N(C(=O)C(C)C)C(=O)C1=C(C)N(C)N=C1C DZVWKNFPXMUIFA-UHFFFAOYSA-N 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- DWFZBUWUXWZWKD-UHFFFAOYSA-N pyridaben Chemical compound C1=CC(C(C)(C)C)=CC=C1CSC1=C(Cl)C(=O)N(C(C)(C)C)N=C1 DWFZBUWUXWZWKD-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a novel acaricide and a preparation method thereof, which are based on the structural foundation of beta-ketonitrile derivative acaricides to be modified, wherein 1,3, 4-substituent groups on pyrazole rings are replaced to be replaced by methyl or ethyl groups, and a polar group with N, O atoms in a ring shape is added in the modified compound, so that the problems that the potential toxicity risk of the electrical-rich heterocycle of the existing beta-ketonitrile derivative acaricides is mainly caused by that unsubstituted heterocycle sites are easy to generate oxidative ring opening, active metabolites with strong electrophilicity are further generated, and the existing beta-ketonitrile derivative acaricides are difficult to dissolve are solved.
Description
Technical Field
The invention relates to the technical field of acaricides, in particular to a novel acaricide and a preparation method thereof.
Background
Mites, especially agricultural mites mainly used for herbivory, are found on crops in all parts of the world, and have the characteristics of small individuals, rapid propagation, short development period, small action range, strong adaptability, high mutation rate, easy generation of drug resistance and the like, and are recognized pest communities which are difficult to prevent. The main agricultural acaricides in the current mainstream mainly comprise organophosphorus, organotin, pyrethroid, pyridaben, propargite, avermectin and other products/species, wherein more than 50% of the agricultural acaricides are used for preventing and controlling fruit mites such as citrus and grapes, but the prevention effect is not as good as before. Since the cyflumetofen and the action mechanism thereof are developed and clarified, the succinic dehydrogenase inhibition acaricide gradually becomes a research hot spot for pest control and fruit application due to the characteristics of high efficiency, low toxicity, safety, low resistance and the like. Therefore, the continuous discovery of novel efficient acaricides with novel structure and unique action mechanism is a requirement of agricultural production.
Succinate Dehydrogenase (SDH), also known as respiratory chain complex ii or succinic-ubiquinone oxidoreductase (SQR), is a critical membrane complex in the respiratory second phase tricarboxylic acid cycle, and succinate dehydrogenase-inhibiting miticides are biological activities on target organisms by binding to the ubiquinone reduction site of the succinate dehydrogenase of the target organism, inhibiting the activity of succinate dehydrogenase, blocking electron transfer, preventing the conversion of ubiquinone to ubiquinol, disrupting tricarboxylic acid cycle, preventing respiration and energy supply of the organism. Has excellent acaricidal activity against mites at various developmental stages including mite eggs.
The succinate dehydrogenase miticide has a brand-new chemical structure, thus having unique action characteristics, excellent bioselectivity and lower risk of cross resistance, and has high selectivity, and is only aimed at succinate dehydrogenase of mites, but has no harm to mammals. Common acaricides acting on the succinate dehydrogenase site of mites include β -ketonitrile derivatives (e.g. cyflumetofen, SYP-10898), cyanovinyl ester derivatives (e.g. cyenopyrafen, NC-510, ethaboxam) and formanilide acaricides (e.g. Pyflubumide), see fig. 1.
The existing beta-ketonitrile derivative acaricide has the potential toxicity risk of the high-electrical-property heterocycle for the group with strong electrical-absorption property, wherein the potential toxicity risk of the high-electrical-property heterocycle is mainly caused by the fact that unsubstituted heterocycle sites are easy to open through oxidization, and further active metabolites with strong electrical-property are generated. In addition, the acaricide has the action mode that the acaricide is hydrolyzed and metabolized into active substances in vivo, but the planar molecules of the existing beta-ketonitrile derivative acaricide, in particular to molecules containing conjugated aromatic rings, are difficult to dissolve due to the close stacking and pi-pi action among the molecules. Therefore, there is a need to propose a novel acaricide and a preparation method thereof to solve the above problems.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a novel acaricide and a preparation method thereof, which are used for solving the problems that the potential toxicity risk of the electrical-rich heterocycle of the existing beta-ketonitrile derivative acaricide is mainly caused by that unsubstituted heterocycle sites are easy to oxidize and open, active metabolites with strong electrophilicity are further generated, and the existing beta-ketonitrile derivative acaricide is difficult to dissolve.
The invention provides a novel acaricide, which is shown in a general formula I:
Wherein, R 1,R2,R3 is CH 3 or C 2H5; x is O, S, NH or H 2; y is O or NH; n=0, 1,2,3.
The invention provides a preparation method of a novel acaricide, which comprises the following synthetic routes:
Further, the method comprises the steps of,
The invention has the following beneficial effects: the invention provides a novel acaricide and a preparation method thereof, which are characterized in that the structural basis of beta-ketonitrile derivative acaricides is transformed, 1,3, 4-site substituents on pyrazole rings are replaced to be changed into methyl or ethyl for substitution, and the substitution of the substituents on the pyrazole rings can not inhibit acaricidal activity as can be seen from the diffraction of cyenopyrafen to ethionazole, and on the contrary, for the group with strong electric absorbability of the pyrazole rings, the potential toxicity risk of the electric-rich heterocycle is mainly caused by the fact that unsubstituted heterocyclic sites are easy to generate oxidative ring opening, and further active metabolites with strong electrophilicity are generated, so that the 4-C of the pyrazole rings are kept in an unsubstituted state when the compounds are transformed. In addition, as the acaricide has the action mode of being hydrolyzed and metabolized into active substances in vivo, the addition of the polar group containing N, O atoms in a ring shape in the modified compound increases the water solubility of the compound, and simultaneously increases hydrogen bond donors and hydrogen bond acceptors, thereby enhancing the binding tightness degree of the acaricide and a target. Generally, planar molecules, particularly those containing conjugated aromatic rings, are less soluble due to the close packing and pi-pi interactions between the molecules. The chemical modification increases the ring structure on the benzene ring, which interferes with the planarity of the molecule, thereby affecting the lattice energy and increasing the solubility of the compound.
Drawings
FIG. 1 is a diagram of several acaricides acting on succinate dehydrogenase;
FIG. 2 is a novel acaricide formula;
FIG. 3 is a protein model constructed using AlphaFold 2.
Detailed Description
Referring to fig. 1 to 3, the embodiment of the present invention provides a novel acaricide, as shown in general formula I:
Wherein, R 1,R2,R3 is CH 3 or C 2H5; x is O, S, NH or H 2; y is O or NH; n=0, 1,2,3.
The embodiment of the invention provides a preparation method of a novel acaricide, which comprises the following synthetic routes:
The preparation method of the novel acaricide comprises a synthetic method of PartII corresponding intermediates:
preparation of N- (3-bromophenyl) -3, 3-dimethylacrylamide:
A solution of 4.15g of sodium hydride in 50mL of THF and 173mmol of sodium hydride in 20.32g of 3-bromoaniline in 118mmol of THF was added to the solution, stirred at 0℃for 45min, then warmed up to 26℃at room temperature over 15min, then 13.12g of 3-methylcrotonyl chloride was added thereto via a dropping funnel, 173mmol was reacted vigorously during the addition, the solution was brown, the mixture was stirred at room temperature for 16h, the reaction was poured into ice water after the consumption of the reactant was completed, the reaction was quenched, the resultant mixture was extracted with methylene chloride, the organic phase was dried over anhydrous MgSO 4, concentrated to a solid by spin evaporation in vacuo, and the solid was recrystallized from n-hexane/ethyl acetate=2:1 to give a pale yellow solid in yield 80%.m.p.106~107℃;1H NMR(500MHz,CDCl3)δ7.86(s,1H),7.44(d,J=7.8Hz,1H),7.24(d,J=8.0Hz,1H),7.19(t,J=8.0Hz,1H),5.72(s,1H),2.25(s,3H),1.94(s,3H);
Preparation of 7-bromo-3, 4-dihydro-4, 4-dimethyl-2 (1H) -quinolinone:
AlCl 3, 13.52g,101mmol under N 2 are introduced into a 500mL round bottom flask at 90℃in an oil bath, 12.83g,50.5mmol of N- (3-bromophenyl) -3, 3-dimethylacrylamide dissolved in CH 2Cl2 are slowly added to AlCl3 by means of a constant pressure dropping funnel over 1.5h with vigorous stirring, and the resulting mixture is stirred at 110-120℃for 6h; after the reaction was completed, the reaction mixture was cooled to room temperature and carefully quenched with ice water; the resulting mixture was extracted with CH 2Cl2, the organic layer was washed sequentially with 2N HCl, water, saturated NaHCO 3 solution, water and brine, the resulting organic phase was dried over anhydrous MgSO 4, filtered and evaporated in vacuo to a white solid; the final product was further isolated and purified in 47% yield, 1H NMR (500 mhz, cdcl 3) delta 8.05 (s, 1H), 7.18 (d, j=8.1 hz, 2H), 6.96 (s, 1H), 2.51 (s, 2H), 1.34 (s, 6H);
preparation of 4, 4-dimethyl-1, 2,3, 4-tetrahydro-7-bromoquinoline:
3.20g,12.6mmol of 7-bromo-3, 4-dihydro-4, 4-dimethyl-2 (1H) -quinolinone and 35ml of anhydrous tetrahydrofuran are stirred at 0 ℃, 0.68g,17mmol of lithium aluminum hydride is added under the protection of nitrogen, and the obtained mixture is stirred at 0 ℃ for 1.5H and then is transferred to room temperature for continuous reaction for 19H; after stopping stirring, carefully pouring a saturated solution of sodium tartrate in ice and quenching the reaction, the resulting mixture was extracted with ethyl acetate, the resulting organic phase was dried over anhydrous MgSO 4, filtered and concentrated in vacuo to give a dark reddish brown oil in yield 94%,1H NMR(500MHz,CDCl3)δ7.05(d,J=8.2Hz,1H),6.75(d,J=7.8Hz,1H),6.62(s,1H),3.99(s,1H),3.35-3.31(m,2H),1.75-1.71(m,2H),1.29(s,6H);
Preparation of 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile:
Into a dry pressure-resistant tube were placed [ Pd2 (all) 2Cl2 ],2mol%,3.7mg,0.01mmol, S-Phos6 mol%,12.3mg,0.03mmol and sodium cyanoacetate 79.5mg,0.75mmol; evacuating the reaction device and injecting argon, and repeating the process three times; then 63mg,0.50mmol and 1.0mL of mesitylene of 4, 4-dimethyl-1, 2,3, 4-tetrahydro-7-bromoquinoline were added under argon countercurrent with a syringe; the tube was capped with a screw cap and stirred at room temperature for 10 minutes; the reaction was stirred in a preheated oil bath at 140 ℃ for 10h; the residue was purified by column chromatography to give 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile as an orange-yellow liquid 32%;1H NMR(500MHz,CDCl3)δ7.19(d,J=7.9Hz,1H),6.57(d,J=7.9Hz,1H),6.46(s,1H),3.63(s,2H),3.38–3.32(m,2H),1.78–1.73(m,2H),1.31(s,6H);
(E) Preparation of 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) -3- (1, 3-dimethyl-1H-pyrazol-5-yl) -3-hydroxyacrylonitrile:
To the reaction flask was added n-heptane 20mL, 1, 3-dimethyl-1H-pyrazole-5-carboxylic acid ethyl ester 0.85g,5.5mol, 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile 5mmol, and dehydrated for 1H; slowly dropwise adding sodium methoxide methanol solution under reflux condition, removing methanol to react, gradually changing the solution into brown yellow, generating yellow solid, adding the reaction solution into ice water 50mL, extracting 10mL multiplied by 3 with ethyl acetate, acidifying the water phase to pH value of 1-2 with hydrochloric acid, extracting with ethyl acetate 50mL multiplied by 3, mixing organic phases, washing with a small amount of sodium bicarbonate aqueous solution and water respectively, drying with anhydrous magnesium sulfate, and removing the yellow solid under reduced pressure to obtain 75% yield;
preparation of the following compounds:
To a 50mL three-port reaction flask equipped with a thermometer and a constant pressure dropping funnel were added (E) -2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) -3- (1, 3-dimethyl-1H-pyrazol-5-yl) -3-hydroxyacrylonitrile (20 mmol) and 300mL of methylene chloride, and the mixture was cooled to 0 to 5℃with stirring, then 24mmol of triethylamine was added, 21mmol of 2, 2-dimethylpropionyl chloride was added dropwise, and after completion of the dropwise addition, the reaction was allowed to continue at room temperature for 15 hours, and then the reaction was stopped, and 20mL of water was added for delamination.
Further, the synthesis method of the Part I corresponding intermediate comprises the following steps:
preparation of ethyl 2, 4-diketopentanoate:
Under ice water bath condition, adding 1.72g of metal sodium into 20mL of absolute ethyl alcohol to prepare 20% sodium ethoxide solution, under ice salt bath condition, adding 25mL of ethanol into a three-mouth bottle, mechanically stirring uniformly, dropwise adding 3.1mL of acetone, 0.04mol of mixed solution of 7.2mL and 0.05mol of diethyl oxalate, 35min, generating a large amount of white solid in the dropwise adding process, heating to 40 ℃ after the dropwise adding process, carrying out constant temperature reaction for 3H, adding 50mL of ice-water mixture into the turbid solution after the constant temperature reaction for dissolving, adjusting pH=3-4 by concentrated hydrochloric acid, extracting 3X 20mL by ethyl acetate, washing an organic phase thereof with saturated saline for 2 times, drying by anhydrous magnesium sulfate, removing the solvent to obtain red oily matters with the yield of 63%.1H NMR (500 MHz, CDCl 3) delta 4.29-4.18 (m, 2H), 4.02 (t, J=10.3 Hz, 2H), 2.17 (d, J=3.3.24H), and 1.32H (3 Hz);
Preparation of ethyl propionyl pyruvate:
5mL of toluene is added into a reaction bottle, then 1.38g of metallic sodium and 0.06mol of absolute ethyl alcohol of 15mL are added dropwise at room temperature, and stirring is carried out for 1h; also at room temperature, dropwise adding 5mL of butanone, 0.056mol, 7.52mL of diethyl oxalate and 0.056mol, stirring for 2 hours, adding concentrated hydrochloric acid to adjust the pH to 3-4, washing by ethyl acetate, washing an organic phase by 3X 20mL with water, and collecting the organic phase to generate ethyl propionylpyruvate; the yield was 58%;1H NMR (500 MHz, CDCl 3) delta 5.33 (s, 1H), 4.39-4.21 (m, 1H), 3.67 (s, 1H), 1.28-1.23 (m, 3H);
Preparation of 3-methyl-1H-hydropyrazole-5-carboxylic acid ethyl ester:
Adding 4.8mL of crude 2, 4-diketone ethyl valerate, 0.034mol and 20mL of dichloromethane solvent into a reaction bottle, mechanically stirring under the ice water bath condition, dropwise adding 1.7mL of 80% hydrazine hydrate solution into the reaction bottle after stabilization, and preserving heat for 1h under the ice water bath condition after the dropwise addition is finished; then removing dichloromethane by desolventizing, adding ethyl acetate for dissolving, washing 3X 20mL with water, drying with anhydrous magnesium sulfate, purifying by column chromatography to obtain red solid, yield 48.3%,1H NMR(500MHz,CDCl3)δ6.56(s,1H),4.58–4.41(m,2H),4.08(td,J=13.8,5.2Hz,1H),2.22(s,3H),1.43–1.31(m,6H);
Preparation of ethyl 3-ethyl-5-pyrazole formate:
Adding 0.034mol of crude propionyl ethyl pyruvate and 20mL of dichloromethane solvent into a reaction bottle, mechanically stirring under ice-water bath condition, dropwise adding 1.7mL of 80% hydrazine hydrate solution into the reaction bottle after stabilization, preserving heat for 1h under ice-water bath condition after dropwise adding, removing dichloromethane by desolventizing, adding ethyl acetate for dissolving, washing 3X 20mL with water, drying with anhydrous magnesium sulfate, purifying by column chromatography to obtain red solid, yield 53%;1H NMR(500MHz,CDCl3)δ6.66(s,1H),4.41(q,J=7.1Hz,2H),2.75(q,J=7.6Hz,2H),1.41(d,J=7.1Hz,3H),1.32(t,J=7.6Hz,3H);
Preparation of ethyl 1, 3-dimethyl-1H-pyrazole-5-carboxylate:
Adding 0.013mol of crude 3-methyl-1H-hydropyrazole-5-ethyl formate and 25mL of dichloromethane solvent into a reaction bottle, dripping 1.35mL of dimethyl sulfate into the reaction liquid, heating to 45 ℃ after dripping for 20min, refluxing for 8H, desolventizing the reaction liquid to remove dichloromethane after refluxing, adding water for dissolving, extracting 3X 20mL with ethyl acetate, washing an organic phase with saturated sodium bicarbonate aqueous solution and saturated saline solution respectively, drying with anhydrous magnesium sulfate, filtering to remove anhydrous magnesium sulfate, and steaming ethyl acetate with a rotary steaming instrument to obtain light yellow oily matter with the yield of 88%;
Preparation of ethyl 1-ethyl-3-methylpyrazole-5-carboxylate:
Adding crude 3-methyl-1H-hydropyrazole-5-ethyl formate (2 g,0.013 mol) and 25mL of methylene dichloride solvent into a reaction bottle, dripping 1.7mL of diethyl sulfate into the reaction liquid, dripping for 20min, heating to 45 ℃ after the dripping is finished, and refluxing for 8H; after completion of the reflux, the reaction solution was desolventized to remove methylene chloride, dissolved in water, extracted with ethyl acetate (3X 20 mL), the organic phase was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated brine, dried over anhydrous magnesium sulfate, distilled to remove ethyl acetate, and purified by column chromatography to give a pale yellow oil, yield 73.8%,1H NMR(500MHz,CDCl3)δ6.62(s,1H),4.53(t,J=7.1Hz,2H),4.34(q,J=7.1Hz,2H),2.29(s,3H),1.43(dd,J=8.5,5.7Hz,3H),1.38(t,J=7.1Hz,3H);
Preparation of 3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid ethyl ester:
13mmol of crude 3-ethyl-5-pyrazolecarboxylic acid ethyl ester and 25mL of dichloromethane solvent are added into a reaction bottle, 1.35mL of dimethyl sulfate is dripped into the reaction liquid, the dripping is carried out for 20min, the temperature is raised to 45 ℃ after the dripping is finished, and the reflux is carried out for 8h; after completion of the reflux, the reaction solution was desolventized to remove methylene chloride, dissolved in water, extracted with ethyl acetate (3X 20 mL), and the organic phase was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated brine, respectively, dried over anhydrous magnesium sulfate, filtered to remove the anhydrous magnesium sulfate, and then ethyl acetate was distilled off with a rotary evaporator to give a pale yellow oily substance in a yield of 79%.
Further, the synthesis method comprises PartII corresponding intermediates:
preparation of N- (3-bromophenyl) -3, 3-dimethylacrylamide:
A solution of 4.15g of sodium hydride in 50mL of THF, 173mmol of the solution was added to a solution of 20.322g of 3-bromoaniline in 50mL of THF, 118mmol of the solution was stirred at 0℃for 45 minutes, then the temperature was raised to 26℃at room temperature over 15 minutes, 3-methylcrotonyl chloride 13.123g,173mmol of the solution was added thereto through a dropping funnel, the reaction was vigorously carried out during the addition, the solution was brown, the mixture was stirred at room temperature for 16 hours, the reaction was poured into ice water after the completion of the consumption, the reaction was quenched, the obtained mixture was extracted with methylene chloride, the organic phase was dried over anhydrous MgSO4, concentrated to a solid by spin evaporation in vacuo, and the solid was recrystallized from n-hexane/ethyl acetate=2:1 to give a pale yellow solid in yield 80%.m.p.106~107℃;1H NMR(500MHz,CDCl3)δ7.86(s,1H),7.44(d,J=7.8Hz,1H),7.24(d,J=8.0Hz,1H),7.19(t,J=8.0Hz,1H),5.72(s,1H),2.25(s,3H),1.94(s,3H);
Preparation of 7-bromo-3, 4-dihydro-4, 4-dimethyl-2 (1H) -quinolinone:
AlCl3, 13.52g,101mmol under N2 protection at 90℃in an oil bath into a 500mL round bottom flask, slowly adding 12.83g,50.5mmol of N- (3-bromophenyl) -3, 3-dimethylacrylamide dissolved in CH2Cl2 to AlCl3 by means of a constant pressure dropping funnel over 1.5h with vigorous stirring, and stirring the resulting mixture at 110-120℃for 6h; after the reaction was completed, the reaction mixture was cooled to room temperature and carefully quenched with ice water; the resulting mixture was extracted with CH2Cl2, the organic layer was washed sequentially with 2N HCl, water, saturated NaHCO3 solution, water and brine, the resulting organic phase was dried over anhydrous MgSO4, filtered and evaporated to a white solid; the final product was further isolated and purified in 47% yield, 1H NMR (500 mhz, cdcl 3) delta 8.05 (s, 1H), 7.18 (d, j=8.1 hz, 2H), 6.96 (s, 1H), 2.51 (s, 2H), 1.34 (s, 6H);
preparation of 4, 4-dimethyl-1, 2,3, 4-tetrahydro-7-bromoquinoline:
3.20g,12.6mmol of 7-bromo-3, 4-dihydro-4, 4-dimethyl-2 (1H) -quinolinone and 35ml of anhydrous tetrahydrofuran are stirred at 0 ℃, 0.68g,17mmol of lithium aluminum hydride is added under the protection of nitrogen, and the obtained mixture is stirred at 0 ℃ for 1.5H and then is transferred to room temperature for continuous reaction for 19H; after stopping stirring, carefully pouring a saturated solution of sodium tartrate in ice and quenching the reaction, the resulting mixture was extracted with ethyl acetate, the resulting organic phase was dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a dark reddish brown oil in yield 94%,1H NMR(500MHz,CDCl3)δ7.05(d,J=8.2Hz,1H),6.75(d,J=7.8Hz,1H),6.62(s,1H),3.99(s,1H),3.35-3.31(m,2H),1.75-1.71(m,2H),1.29(s,6H);
Preparation of 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile:
Into a dry pressure-resistant tube were placed [ Pd2 (all) 2Cl2],2mol%,3.7mg,0.01mmol, S-Phos6 mol%,12.3mg,0.03mmol and sodium cyanoacetate 79.5mg,0.75mmol; evacuating the reaction device and injecting argon, and repeating the process three times; then 63mg,0.50mmol and 1.0mL of mesitylene of 4, 4-dimethyl-1, 2,3, 4-tetrahydro-7-bromoquinoline were added under argon countercurrent with a syringe; the tube was capped with a screw cap and stirred at room temperature for 10 minutes; the reaction was stirred in a preheated oil bath at 140 ℃ for 10h; the residue was purified by column chromatography to give 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile as an orange-yellow liquid 32%;1H NMR(500MHz,CDCl3)δ7.19(d,J=7.9Hz,1H),6.57(d,J=7.9Hz,1H),6.46(s,1H),3.63(s,2H),3.38–3.32(m,2H),1.78–1.73(m,2H),1.31(s,6H);
(E) Preparation of 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) -3- (1, 3-dimethyl-1H-pyrazol-5-yl) -3-hydroxyacrylonitrile:
To the reaction flask was added n-heptane 20mL, 1, 3-dimethyl-1H-pyrazole-5-carboxylic acid ethyl ester 0.85g,5.5mol, 2- (4, 4-dimethyl-1, 2,3, 4-tetrahydroquinolin-7-yl) acetonitrile 5mmol, and dehydrated for 1H; slowly dropwise adding sodium methoxide methanol solution under reflux condition, removing methanol to react, gradually changing the solution into brown yellow, generating yellow solid, adding the reaction solution into ice water 50mL, extracting 10mL multiplied by 3 with ethyl acetate, acidifying the water phase to pH value of 1-2 with hydrochloric acid, extracting with ethyl acetate 50mL multiplied by 3, mixing organic phases, washing with a small amount of sodium bicarbonate aqueous solution and water respectively, drying with anhydrous magnesium sulfate, and removing the yellow solid under reduced pressure to obtain 75% yield;
preparation of the following compounds:
To a 50mL three-port reaction flask equipped with a thermometer and a constant pressure dropping funnel were added compound 8 (20 mmol) and 300mL methylene chloride, stirred and cooled to 0-5℃and then 24mmol of triethylamine was added, 21mmol of 2, 2-dimethylpropionyl chloride was added dropwise, the reaction was stopped after the completion of the dropwise addition, and after the reaction was continued at room temperature for 15 hours, 20mL of water was added for delamination, the aqueous layer was extracted with methylene chloride, the organic layers were combined, washed with a saturated sodium chloride solution, then water-washed and concentrated, and the residue was recrystallized with n-hexane to obtain the objective compound.
The invention has the following beneficial effects: the invention provides a novel acaricide and a preparation method thereof, which are characterized in that the structural basis of beta-ketonitrile derivative acaricides is transformed, 1,3, 4-site substituents on pyrazole rings are replaced to be changed into methyl or ethyl for substitution, and the substitution of the substituents on the pyrazole rings can not inhibit acaricidal activity as can be seen from the diffraction of cyenopyrafen to ethionazole, and on the contrary, for the group with strong electric absorbability of the pyrazole rings, the potential toxicity risk of the electric-rich heterocycle is mainly caused by the fact that unsubstituted heterocyclic sites are easy to generate oxidative ring opening, and further active metabolites with strong electrophilicity are generated, so that the 4-C of the pyrazole rings are kept in an unsubstituted state when the compounds are transformed. In addition, as the acaricide has the action mode of being hydrolyzed and metabolized into active substances in vivo, the addition of the polar group containing N, O atoms in a ring shape in the modified compound increases the water solubility of the compound, and simultaneously increases hydrogen bond donors and hydrogen bond acceptors, thereby enhancing the binding tightness degree of the acaricide and a target. Generally, planar molecules, particularly those containing conjugated aromatic rings, are less soluble due to the close packing and pi-pi interactions between the molecules. The chemical modification increases the ring structure on the benzene ring, which interferes with the planarity of the molecule, thereby affecting the lattice energy and increasing the solubility of the compound.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present application. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (2)
1. A novel acaricide is characterized by being shown in a general formula I:
Wherein, R 1,R2,R3 is CH 3 or C 2H5; x is O, S, NH or H 2; y is O or NH; n=0, 1,2,3.
2. The preparation method of the novel acaricide is characterized by comprising the following synthetic routes:
preparation of ethyl 2, 4-diketopentanoate:
Under ice water bath condition, adding 1.72g of metal sodium into 20mL of absolute ethyl alcohol to prepare 20% sodium ethoxide solution, under ice salt bath condition, adding 20% sodium ethoxide solution into a three-mouth bottle, adding 25mL of ethanol, mechanically stirring uniformly, dropwise adding 3.1mL of acetone, 0.04mol of mixed solution of 7.2mL of diethyl oxalate and 0.05mol of mixed solution, carrying out 35min, generating a large amount of white solid in the dropwise adding process, heating to 40 ℃ after the dropwise adding process, carrying out constant temperature reaction for 3h, adding 50mL of ice water mixture into the turbid solution after the constant temperature reaction for dissolving, adjusting pH value to 3-4 by concentrated hydrochloric acid, extracting 20X 3mL by ethyl acetate, washing an organic phase thereof for 2 times by saturated saline, drying by anhydrous magnesium sulfate, removing the solvent to obtain red oily matter, and obtaining the yield of 50mL of ice 63%.1H NMR(500MHz,CDCl3)δ4.29–4.18(m,2H),4.02(t,J=10.3Hz,2H),2.17(d,J=13.3Hz,3H),1.32–1.24(m,3H).
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