CN102690241B - Benzoyl urea compound containing isoxazoline and isoxazole structure, and preparation and application thereof - Google Patents
Benzoyl urea compound containing isoxazoline and isoxazole structure, and preparation and application thereof Download PDFInfo
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- CN102690241B CN102690241B CN201110070875.5A CN201110070875A CN102690241B CN 102690241 B CN102690241 B CN 102690241B CN 201110070875 A CN201110070875 A CN 201110070875A CN 102690241 B CN102690241 B CN 102690241B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- -1 Benzoyl urea compound Chemical class 0.000 title claims abstract description 34
- 125000000842 isoxazolyl group Chemical group 0.000 title abstract description 9
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 125000003971 isoxazolinyl group Chemical group 0.000 claims description 10
- 241000500437 Plutella xylostella Species 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims 2
- 239000003905 agrochemical Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 abstract description 7
- 230000000749 insecticidal effect Effects 0.000 abstract description 7
- 241000238631 Hexapoda Species 0.000 abstract description 4
- 125000005843 halogen group Chemical group 0.000 abstract description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
- 125000004185 ester group Chemical group 0.000 abstract description 3
- 125000002541 furyl group Chemical group 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 150000002367 halogens Chemical class 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 125000002098 pyridazinyl group Chemical group 0.000 abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 abstract description 3
- 125000001544 thienyl group Chemical group 0.000 abstract description 3
- 125000001425 triazolyl group Chemical group 0.000 abstract description 3
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 abstract description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 abstract description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 abstract description 2
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 abstract 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 abstract 1
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 150000001356 alkyl thiols Chemical class 0.000 abstract 1
- 125000001841 imino group Chemical group [H]N=* 0.000 abstract 1
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 42
- 239000007787 solid Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- 229910052799 carbon Inorganic materials 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- 238000001035 drying Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 239000003513 alkali Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 230000002194 synthesizing effect Effects 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229960001866 silicon dioxide Drugs 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 238000007598 dipping method Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 235000011150 stannous chloride Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000409991 Mythimna separata Species 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 150000001555 benzenes Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000003810 ethyl acetate extraction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 235000009973 maize Nutrition 0.000 description 3
- FSKSLWXDUJVTHE-UHFFFAOYSA-N n-[(4-fluorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=CC=C(F)C=C1 FSKSLWXDUJVTHE-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
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- 125000003944 tolyl group Chemical group 0.000 description 3
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 2
- PCKNFPQPGUWFHO-SXBRIOAWSA-N (Z)-flucycloxuron Chemical compound FC1=CC=CC(F)=C1C(=O)NC(=O)NC(C=C1)=CC=C1CO\N=C(C=1C=CC(Cl)=CC=1)\C1CC1 PCKNFPQPGUWFHO-SXBRIOAWSA-N 0.000 description 2
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 0 C*c1cccc(*)c1[N+]([O-])[Zn] Chemical compound C*c1cccc(*)c1[N+]([O-])[Zn] 0.000 description 2
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- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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- 150000007945 N-acyl ureas Chemical class 0.000 description 2
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- 150000001299 aldehydes Chemical class 0.000 description 2
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- 150000000499 3-oxazolines Chemical class 0.000 description 1
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- 239000000047 product Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a benzoyl urea compound containing isoxazoline and isoxazole structure, and a preparation and application thereof. The compound is shown as a general formula (I). R1 and R2 respectively represent hydrogen and halogen atoms; R3 represents hydrogen, halogen atoms, C1-10 alkyl group and C1-10 halogenated alkyl group; R4, R5, R6 and R7 respectively represent hydrogen, C1-10 alkyl group, cyan group, ester group, C1-10 halogenated alkyl group, phenyl group, thienyl, pyridyl, pyridazinyl, furyl, triazolyl, naphthyl, chroman, 2,3-dihydro-1,4-benzo dioxazine, 4H-1,3-benzo dioxazine, 2,3-dihydro-coumarone, coumarone, 1,3-benzoxazole, 1,2-benzisoxazole and benzimidazole, and each group is unsubstituted or substituted by or more groups selected from the group containing halogen, C1-4 alkyl group, C1-4 alkoxy, C1-4 halogenated alkyl group, C1-4 alkoxyl alkyl group, C1-4 alkylthiol, C1-4 alkyl sulfinyl, C1-4 alkyl sulfonyl, nitryl, cyan, hydroxy group, carboxyl, C1-4 alkyl carbonyl and imino group. The compound of the invention has good insecticidal activity, and can be widely applied to insect control of crops.
Description
Technical field
The present invention relates to Han isoxazoline with the benzoyl urea compound of isoxazole structure and preparation method and as pesticides application.
Background technology
US-3450747 and US-3748356 disclose benzoylphenyl carbamide compounds and insecticidal activity thereof; US-475113; US-4497822 and US-4666942 disclose containing N-alkylthio, arylthio and N-thiocarbamate alkyl ester benzoylphenyl carbamide derivative and insecticidal activity thereof.CN1891686A discloses preparation and the application of N-thio aminobenzformyl phenylurea compound.
US-4609676 discloses the benzoylphenyl carbamide compound A of a class containing oxime ether, and wherein commercialization kind flucycloxuron (Flucycloxuron, B) belongs to this structure.
CN101602695 discloses benzoylphenyl carbamide compound C and preparation and the application of a class containing aldehydes or ketones 9 oxime derivate structure.
WO2002076956 discloses the phenylbenzene 1 of a Lei isoxazoline structure, 3-oxazoline compounds D and insecticidal activity thereof.
Summary of the invention
The object of this invention is to provide a kind of new Han isoxazoline with the benzoyl urea compound of isoxazole structure and preparation and application.The compound that this compounds is known from those is different, and structure is completely novel, have than similar known ureide derivative compound more superior, insecticidal activity that scope is wider.
Han isoxazoline of the present invention is with the benzoyl urea compound of isoxazole structure is the compound with structure shown in following general formula (I):
In formula, R
1, R
2represent independently respectively hydrogen, halogen atom.
R
3represent hydrogen, halogen atom, 1-10 carbon alkyl, 1-10 halocarbon substituted alkyl.
R
4, R
5, R
6, R
7represent independently respectively hydrogen, 1-10 carbon alkyl, cyano group, ester group, 1-10 halocarbon substituted alkyl, phenyl, thienyl, pyridyl, pyridazinyl, furyl, triazolyl, naphthyl, chroman, 2, 3-dihydro-1, 4-Ben Bing dioxazine, 4H-1, 3-Ben Bing dioxazine, 2, 3-dihydro-cumarone, cumarone, benzothiazole, 1, 3-benzoxazole, 1, 2-benzoisoxazole or benzoglyoxaline, each group is unsubstituted, or replaced by one or more following radicals: halogen, 1-4 carbon alkyl, 1-4 carbon alkoxyl group, 1-4 halocarbon substituted alkyl, 1-4 carbon halogenated alkoxy, 1-4 carbon alkoxyalkyl, 1-4 carbon alkylthio, 1-4 carbon alkyl sulphinyl, 1-4 carbon alkyl sulphonyl, nitro, cyano group, hydroxyl, carboxyl, 1-4 carbon alkyl-carbonyl, 1-4 carbon alkoxy carbonyl or imido grpup.
Han isoxazoline of the present invention is with in the benzoyl urea compound of isoxazole structure, preferably: R
1, R
2it is 2,6-difluoro; R
3represent hydrogen, fluorine, chlorine; R
4, R
5, R
6, R
7represent independently respectively hydrogen, 1-10 carbon alkyl, cyano group, ester group, 1-10 halocarbon substituted alkyl, phenyl, thienyl, pyridyl, pyridazinyl, furyl, triazolyl, naphthyl, each group is unsubstituted, or is replaced by one or more following radicals: halogen, 1-4 carbon alkyl, 1-4 carbon alkoxyl group, 1-4 halocarbon substituted alkyl, nitro, cyano group, hydroxyl, carboxyl, 1-4 carbon alkyl-carbonyl, 1-4 carbon alkoxy carbonyl.
The benzoyl urea compound (I) of described Han isoxazoline structure can be as follows a preparation: by the paranitrobenzaldehyde oxime replacing and chlorination reagent (as NCS, t-butyl hypochlorate) reaction obtain replace alpha-chloro paranitrobenzaldehyde oxime, then in organic solvent take alkali as acid binding agent and the olefine reaction of replacement generate compound (I-a1), compound (I-a1) reduces through iron, or two hydrated stannous chloride reduction or obtain compound (I-a2) with palladium catalyzed hydrogenation, again with 2, the addition of 6-disubstituted benzenes formyl radical isocyanic ester can make the benzoyl urea compound (I-a) of Han isoxazoline structure.Organic solvent is toluene, benzene, hexanaphthene, acetonitrile, methylene dichloride, chloroform, tetracol phenixin, acetone, tetrahydrofuran (THF), ether, dioxane, DMF (DMF) or DMSO (dimethyl sulfoxide (DMSO)); Mineral alkali is NaOH, KOH, Na
2cO
3, K
2cO
3, NaHCO
3, KHCO
3; Organic bases is pyridine, triethylamine or 4-N, N dimethylamine yl pyridines.
Method one:
The benzoyl urea compound (I) of described Han isoxazoline structure two preparations as follows: aldehyde is obtained to aldoxime take mineral alkali or organic bases as acid binding agent reacts with oxammonium hydrochloride in organic solvent, obtain again the aldoxime of alpha-chloro according to the method for the alpha-chloro paranitrobenzaldehyde oxime that in method one, preparation replaces, then in organic solvent take alkali as acid binding agent and the p-nitrophenyl ethylene reaction of replacement generate compound (I-b1), compound (I-b1) reduces through iron, or two hydrated stannous chloride reduction or obtain compound (I-b2) with palladium catalyzed hydrogenation, again with 2, the addition of 6-disubstituted benzenes formyl radical isocyanic ester can make the benzoyl urea compound (I-b) of Han isoxazoline structure.Organic solvent is toluene, benzene, hexanaphthene, acetonitrile, methylene dichloride, chloroform, tetracol phenixin, acetone, tetrahydrofuran (THF), ether, dioxane, DMF (DMF) or DMSO (dimethyl sulfoxide (DMSO)); Mineral alkali is NaOH, KOH, Na
2cO
3, K
2cO
3, NaHCO
3, KHCO
3; Organic bases is pyridine, triethylamine or 4-N, N dimethylamine yl pyridines.
Method two:
The benzoyl urea compound (I) of described Han isoxazole structure can be as follows three preparations: by the paranitrobenzaldehyde oxime replacing and chlorination reagent (as NCS, t-butyl hypochlorate) reaction obtain replace alpha-chloro paranitrobenzaldehyde oxime, then in organic solvent take alkali as acid binding agent and the alkynes reacting generating compound (I-c1) of replacement, compound (I-c1) reduces through iron, or two hydrated stannous chloride reduction or obtain compound (I-c2) with palladium catalyzed hydrogenation, again with 2, the addition of 6-disubstituted benzenes formyl radical isocyanic ester can make the benzoyl urea compound (I-c) of Han isoxazole structure.Organic solvent is toluene, benzene, hexanaphthene, acetonitrile, methylene dichloride, chloroform, tetracol phenixin, acetone, tetrahydrofuran (THF), ether, dioxane, DMF (DMF) or DMSO (dimethyl sulfoxide (DMSO)); Mineral alkali is NaOH, KOH, Na
2cO
3, K
2cO
3, NaHCO
3, KHCO
3; Organic bases is pyridine, triethylamine or 4-N, N dimethylamine yl pyridines.
Method three:
The present invention also comprises enantiomer and the racemic isomer of these compounds.
The present invention goes back the compound of listing in free list 1 and illustrates, but does not limit the present invention.
The compound that Han isoxazoline provided by the invention is known from those with the benzoyl urea compound of isoxazole structure is different, and structure is completely novel, have than similar known ureide derivative compound more superior, insecticidal activity that scope is wider.
The compound of general formula of the present invention (I) has excellent insecticidal activity, can be used for preventing and treating lepidopteran class, Coleoptera class, Diptera class, Orthoptera class and Homoptera class pest, is particularly suitable for preventing and treating lepidopteran class pest.
The compound of general formula of the present invention (I) can directly use, and also can add that the upper carrier of accepting of agricultural uses, also can with other sterilants and (or) the composite use of miticide.
Embodiment
Further illustrate the present invention below in conjunction with embodiment, in following embodiment, fusing point is not calibrated, and yield is without optimization.
Embodiment 1:I-a-1～I-a-14's is synthetic
Synthesizing of 1-chlorine paranitrobenzaldehyde oxime adds 3.30g paranitrobenzaldehyde oxime in 250mL there-necked flask, Virahol/1, and 2-ethylene dichloride mixed solvent 50mL, stirs and makes its dissolving.Under cryosel is cooling, drip 1 of t-butyl hypochlorate 2.39g, 2-dichloroethane solution.Stir after 1 hour, revolve desolventizing, obtain 1-chlorine paranitrobenzaldehyde oxime 3.91g, thick yield is 97.5%.Fusing point is: 122-124 ℃.
1H?NMR(300MHz，CDCl
3)：δ8.27(d，2H，J＝9.0Hz，Ar-H)，8.17(s，1H，N-OH)，8.05(d，2H，J＝9.0Hz，Ar-H)。
The 5-tertiary butyl-3-p-nitrophenyl-4, in the synthetic 100mL four-hole bottle of 5-dihydro-isoxazole, add 1.00g1-chlorine paranitrobenzaldehyde oxime, 40mL methylene dichloride makes its dissolving, add again 0.50g 3,3-dimethyl-1-butylene, add the dichloromethane solution of 0.51g triethylamine, dropwise room temperature reaction and spend the night.Reaction finish after, successively with 5% dilute hydrochloric acid wash, saturated common salt wash, anhydrous magnesium sulfate drying.Filter, filtrate is spin-dried for, and crosses silicagel column and obtains yellow solid I-a1-1 (0.78g), and yield is 62.9%, fusing point: 150-154 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.25(d，J＝8.7Hz，2H，Ar-H)，7.83(d，J＝8.7Hz，2H，Ar-H)，4.55(t，J＝10.2Hz，1H，OCH)，3.25(dd，J＝16.9，11.3Hz，1H，CH
2)，3.10(dd，J＝16.8，9.3Hz，1H，CH
2)，0.98(s，9H，C(CH
3)
3).
The 5-tertiary butyl-3-p-amino phenyl-4, in the synthetic 100mL there-necked flask of 5-dihydro-isoxazole, adds 0.50g I-a1-1,30mL ethyl acetate, and 2mL acetic acid, 1mL water, is heated to 70 ℃, adds 0.45g reduced iron powder, and TLC detection reaction is complete.Stopped reaction, filters, and filtrate is washed till neutrality with saturated sodium bicarbonate solution, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, desolventizing is revolved in decompression, obtains yellow liquid I-a2-10.40g, and yield is 90.9%.
1H?NMR(400MHz，CDCl
3)δ7.47(d，J＝8.5Hz，2H，Ar-H)，6.66(d，J＝8.6Hz，2H，Ar-H)，4.38(t，J＝10.0Hz，1H，OCH)，3.86(brs，2H，NH
2)，3.17(dd，J＝16.7，11.1Hz，1H，CH
2)，3.02(dd，J＝16.7，9.0Hz，1H，CH
2)，0.95(s，9H，C(CH
3)
3).
In the synthetic 50mL there-necked flask of target compound I-a-1, add 0.38g I-a2-1,20mL dichloromethane solution, adds 0.32g 2 under room temperature, the dichloromethane solution of 6-difluoro benzoyl isocyanic ester, and stirring at room temperature 8 hours is to reacting completely.With ethyl acetate and sherwood oil recrystallization, obtain white solid I-a-1 (0.43g), yield is 61.4%.Fusing point: 197-199 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.54(brs，1H，CONHCO)，8.80(brs，1H，CONHAr)，7.63(d，J＝8.4Hz，2H，Ar-H)，7.51-7.58(m，3H，Ar-H)，7.06(t，J＝8.5Hz，2H，Ar-H)，4.45(t，J＝10.1Hz，1H，OCH)，3.17(dd，J＝16.8，11.4Hz，1H，CH
2)，3.07(dd，J＝16.6，9.2Hz，1H，CH
2)，0.98(s，9H，C(CH
3)
3).Anal.Calcd.for?C
21H
21F
2N
3O
3：C，62.84；H，5.27；N，10.47.Found：C，62.72；H，5.33；N，10.62.
The preparation method of reference object Compound I-a-1, has synthesized target compound I-a-2～I-a-14.
The synthetic white solid of target compound I-a-2, yield 54.3%, fusing point: 266-268 ℃.
1H?NMR(400MHz，d6-DMSO)：δ11.47(brs，1H，CONHCO)，10.30(brs，1H，CONHAr)，7.52-7.74(m，5H，Ar-H)，7.36-7.49(m，2H，Ar-H)，7.14-7.31(m，4H，Ar-H)，5.71(t，J＝9.5Hz，1H，OCH)，3.83(dd，J＝17.1，10.8Hz，1H，CH
2)，3.36(dd，J＝17.1，8.5Hz，1H，CH
2).Anal.Calcd.for?C
23H
16F
3N
3O
3：C，62.87；H，3.67；N，9.56.Found：C，62.71；?H，3.79；N，9.33.
The synthetic white solid of target compound I-a-3, yield 73.6%, fusing point: 175-178 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.59(brs，1H，CONHCO)，9.54(brs，1H，CONHAr)，7.48-7.62(m，5H，Ar-H)，7.06(t，J＝8.4Hz，2H，Ar-H)，4.70-4.78(m，1H，OCH)，3.39(dd，J＝16.3，10.3Hz，1H，CH
2C＝N)，2.96(dd，J＝16.4，8.2Hz，1H，CH
2C＝N)，1.77-1.81(m，1H，OCHCH
2CH
2)，1.58-1.68(m，1H，OCHCH
2CH
2)，1.36-1.51(m，4H，CH
2(CH
2)
2CH
3)，0.93(t，J＝6.8Hz，3H，CH
2CH
3).Anal.Calcd.for?C
21H
21F
2N
3O
3：C，62.84；H，5.27；N，10.47.Found：C，62.84；H，5.22；N，10.33.
The synthetic white solid of target compound I-a-4, yield 56.1%, fusing point: 230 ℃ (decomposition).
1HNMR(400MHz，d6-DMSO)：δ11.49(brs，1H，CONHCO)，10.31(brs，1H，CONHAr)，7.56-7.72(m，5H，Ar-H)，7.25(t，J＝8.2Hz，2H，Ar-H)，4.97(dd，J＝9.7，4.4Hz，1H，OCH)，3.65-3.76(m，2H，CH
2Br)，3.54-3.60(m，1H，CH
2C＝N)，3.19-3.25(m，1H，CH
2C＝N).Anal.Calcd.for?C
18H
14BrF
2N
3O
3：C，49.33；H，3.22；N，9.59.Found：C，49.32；H，3.32；N，9.39.
The synthetic white solid of target compound I-a-5, yield 80.0%, fusing point: 178-180 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.57(brs，1H，CONHCO)，8.58(brs，1H，CONHAr)，7.53-7.64(m，5H，Ar-H)，7.06(t，J＝8.5Hz，2H，Ar-H)，4.70-4.77(m，1H，OCH)，3.39(dd，J＝16.3，10.3Hz，1H，CH
2C＝N)，2.96(dd，J＝16.3，8.2Hz，1H，CH
2C＝N)，1.76-1.87(m，1H，OCHCH
2CH
2)，1.55-1.64(m，1H，OCHCH
2CH
2)，1.28-1.50(m，12H，CH
2(CH
2)
6CH
3)，0.88(t，J＝6.2Hz，3H，CH
2CH
3).Anal.Calcd.for?C
25H
29F
2N
3O
3：C，65.63；H，6.39；N，9.18.Found：C，65.55；H，6.26；N，9.32.
The synthetic white solid of target compound I-a-6, yield 63.6%, fusing point: 227-229 ℃.
1H?NMR(400MHz，d6-DMSO)：δ11.52(brs，1H，CONHCO)，10.34(brs，1H，CONHAr)，7.55-7.82(m，5H，Ar-H)，7.26(t，J＝8.0Hz，2H，Ar-H)，5.81(dd，J＝10.1，5.1Hz，1H，OCH)，3.82-3.97(m，2H，CH
2).Anal.Calcd.for?C
18H
12F
2N
4O
3：C，58.38；H，3.27；N，15.13.Found：C，58.14；H，3.24；N，14.99.
The synthetic white solid of target compound I-a-7, yield 72.7%, fusing point: 196-198 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.60(brs，1H，CONHCO)，8.84(brs，1H，CONHAr)，7.65(d，J＝8.6Hz，2H，Ar-H)，7.50-7.61(m，3H，Ar-H)，7.07(t，J＝8.6Hz，2H，Ar-H)，5.21(dd，J＝10.3，7.7Hz，1H，OCH)，3.83(s，3H，COOCH
3)，3.60-3.74(m，2H，CH
2).Anal.Calcd.for?C
19H
15F
2N
3O
5：C，56.58；H，3.75；N，10.42.Found：C，56.33；H，3.77；N，10.48.
The synthetic white solid of target compound I-a-8, yield 82.8%. fusing point: 156-158 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.58(brs，1H，CONHCO)，9.10(brs，1H，CONHAr)，7.64(d，J?＝8.6Hz，Ar-H)，7.53-7.57(m，3H，Ar-H)，7.06(t，J＝8.5Hz，2H，Ar-H)，4.87-4.94(m，1H，OCH)，3.51-3.66(m，4H，CH
2OCH
2CH
2)，3.39(dd，J＝16.5，10.7Hz，1H，CH
2C＝N)，3.24(dd，J＝16.6，7.4Hz，1H，CH
2C＝N)，1.53-1.60(m，2H，OCH
2CH
2CH
2CH
3)，1.32-1.41(m，2H，CH
2CH
2CH
3)，0.91(t，J＝7.3Hz，3H，CH
2CH
3).Anal.Calcd.for?C
22H
23F
2N
3O
4：C，61.25；H，5.37；N，9.74.Found：C，61.30；H，5.33；N，9.64.
The synthetic white solid of target compound I-a-9, yield 88.2%, fusing point: 175-177 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.57(brs，1H，CONHCO)，8.56(brs，1H，CONHAr)，7.48-7.73(m，5H，Ar-H)，7.07(t，J＝8.7Hz，2H，Ar-H)，4.89-4.97(m，1H，OCH)，3.97(q，J＝8.6Hz，2H，OCH
2CF
3)，3.79-3.84(m，2H，CH
2O)，3.43(dd，J＝16.7，9.2Hz，1H，CH
2C＝N)，3.43(dd，J＝16.7，7.5Hz，1H，CH
2C＝N).Anal.Calcd.for?C
20H
16F
5N
3O
4：C，52.52；H，3.53；N，9.19.Found：C，52.34；H，3.66；N，9.31.
The synthetic white solid of target compound I-a-10, yield 82.4%. fusing point: 197-199 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.59(brs，1H，CONHCO)，9.00(brs，1H，CONHAr)，7.66(d，J＝8.6Hz，2H，Ar-H)，7.52-7.59(m，3H，Ar-H)，7.32-7.41(m，5H，Ar-H)，7.07(t，J＝8.5Hz，2H，Ar-H)，5.75(dd，J＝10.8，8.4Hz，1H，OCH)，3.79(dd，J＝16.6，11.0Hz，1H，CH
2)，3.35(dd，J＝16.6，8.3Hz，1H，CH
2).Anal.Calcd.for?C
23H
17F
2N
3O
3：C，65.55；H，4.07；N，9.97.Found：C，65.78；H，3.97；N，9.71.
The synthetic white solid of target compound I-a-11, yield 72.9%, fusing point 205-208 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.58(brs，1H，CONHCO)，9.34(brs，1H，CONHAr)，7.49-7.61(m，7H，Ar-H)，7.38(t，J＝7.6Hz，2H，Ar-H)，7.26-7.33(m，1H，Ar-H)，7.05(t，J＝8.4Hz，2H，Ar-H)，3.50(q，J＝16.4，2H，CH
2C＝N)，1.82(s，3H，CH
3).Anal.Calcd.for?C
24H
19F
2N
3O
3：C，66.20；H，4.40；N，9.65.Found：C，65.98；H，4.49；N，9.58.
The synthetic white solid of target compound I-a-12, yield 70.4%, fusing point: 187-189 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.57(brs，1H，CONHCO)，9.28(brs，1H，CONHAr)，7.50-7.62(m，5H，Ar-H)，7.06(t，J＝8.4Hz，2H，Ar-H)，3.05(s，2H，CH
2C＝N)，1.82(d，J＝5.6Hz，4H)，1.63-1.71(m，2H)，1.49(s，4H).Anal.Calcd.for?C
22H
21F
2N
3O
3：C，63.91；H，5.12；N，10.16.Found：C，63.67；H，4.98；N，10.26.
The synthetic white solid of target compound I-a-13, yield 74.5%, fusing point 193-195 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.57(brs，1H，CONHCO)，9.28(brs，1H，CONHAr)，7.47-7.60(m，5H，Ar-H)，7.05(t，J＝8.4Hz，2H，Ar-H)，3.26(s，2H，CH
2C＝N)，2.13-2.21(m，2H)，1.74-1.90(m，6H).Anal.Calcd.for?C
21H
19F
2N
3O
3：C，63.15；H，4.80；N，10.52.Found：C，63.11；H，4.78；N，10.34.
The synthetic white solid of target compound I-a-14, yield 84.3%, fusing point: 216-218 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.54(brs，1H，CONHCO)，8.83(brs，1H，CONHAr)，7.67(d，J＝8.6Hz，2H，Ar-H)，7.51-7.59(m，3H，Ar-H)，7.06(t，J＝8.5Hz，2H，Ar-H)，5.23(dd，J＝8.6，4.6Hz，1H，OCH)，4.04(t，J＝8.3Hz，1H，CHC＝N)，2.19(dd，J＝12.0，5.0Hz，1H，OCHCH
2)，1.68-1.96(m，4H，CH
2CH
2CHC＝N)，1.48-1.55(m，1H，OCHCH
2).HRMS(ESI)m/z?calcd?for?C
20H
17F
2N
3O
3：(M+Na)
+408.1130，found408.1138.
Embodiment 2:I-b-1 and I-b-2's is synthetic
In the synthetic 50mL there-necked flask of p-Fluorobenzenecarboxaldehyde oxime, add 1.24g p-Fluorobenzenecarboxaldehyde, 30mL tetrahydrofuran (THF), then add 0.83g oxammonium hydrochloride, and 0.95g pyridine, it is complete that stirring at room temperature detects raw material reaction to TLC.Stopped reaction, adds water, and is extracted with ethyl acetate.Organic layer is washed with dilute hydrochloric acid, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, revolve desolventizing, obtain faint yellow solid 1.32g, yield is 95.0%, fusing point: 86-88 ℃.
3-, to fluorophenyl-5-p-nitrophenyl-4, in the synthetic 50mL there-necked flask of 5-dihydro-isoxazole, adds p-Fluorobenzenecarboxaldehyde oxime 0.68g, Virahol/1, and 2-ethylene dichloride mixed solvent 12mL, stirs and makes its dissolving.Under cryosel is cooling, drip 1 of t-butyl hypochlorate 0.63g, 2-dichloroethane solution, stirred after 1 hour, revolved desolventizing, obtained yellow solid 0.83g, and thick yield is 97.6%.Without purification, directly carry out the next step.
In 100mL there-necked flask, add 0.83g 1-chlorine p-Fluorobenzenecarboxaldehyde oxime and p-nitrophenyl ethene 0.69g, methylene dichloride 30mL, 0.53g triethylamine, dropwises, room temperature reaction.Reaction finish after (TLC detections), successively with 5% dilute hydrochloric acid wash, saturated common salt wash, anhydrous magnesium sulfate drying.Filter, filtrate is spin-dried for, and crosses silicagel column and obtains faint yellow solid I-b1-1 (0.78g), and yield is 59.1%, fusing point: 87-90 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.24(d，J＝8.6Hz，2H，Ar-H)，7.67(dd，J＝8.0，5.8Hz，2H，Ar-H)，7.57(d，J＝8.5Hz，2H，Ar-H)，7.11(t，J＝8.5Hz，2H，Ar-H)，5.84(dd，J＝11.0，7.7Hz，1H，OCH)，3.87(dd，J＝16.6，11.2Hz，1H，CH
2)，3.29(dd，J＝16.6，7.6Hz，1H，CH
2).
3-, to fluorophenyl-5-p-amino phenyl-4, in the synthetic 100mL there-necked flask of 5-dihydro-isoxazole, adds 0.95g I-b1-1,50mL ethanol, and 2.62g bis-hydrated stannous chlorides, reflux is complete to TLC detection reaction.Stopped reaction, adds water, and adds ethyl acetate extraction.Organic layer is successively with saturated sodium bicarbonate solution, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, desolventizing is revolved in decompression, obtains yellow solid I-b2-1 (0.83g), and yield is 97.8%, fusing point: 85-87 ℃.
1h NMR (400MHz, CDCl
3): δ 7.62-7.70 (m, 2H, Ar-H), 7.18 (d, J=7.8Hz, 2H, Ar-H), 7.10 (t, J=8.3Hz, 2H, Ar-H), 6.68 (d, J=7.6Hz, 2H, Ar-H), 5.63 (t, J=9.7Hz, 1H, OCH), 3.66 (dd, J=16.6,10.6Hz, 1H, CH
2), 3.30 (dd, J=16.3,8.9Hz, 1H, CH
2). product purity can directly be carried out the next step.
The synthetic preparation method with reference to I-a-1 of target compound I-b-1 is synthetic, obtains white solid I-b-1, and yield is 87.2%, fusing point: 192-194 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.48(brs，1H，CONHCO)，9.38(brs，1H，CONHAr)，7.69(dd，J＝8.6，5.4Hz，2H，Ar-H)，7.41-7.58(m，3H，Ar-H)，7.32(d，J＝8.4Hz，2H，Ar-H)，7.11(t，J＝8.6Hz，2H，Ar-H)，7.03(t，J＝8.4Hz，2H，Ar-H)，5.70-5.75(m，1H，OCH)，3.75(dd，J＝16.6，10.9Hz，1H，CH
2)，3.30(dd，J＝16.6，8.4Hz，1H，CH
2).HRMS(ESI)m/z?calcd?forC
23H
16F
3N
3O
3(M+Na)
+462.1036，found?462.1036.
The 3-tertiary butyl-5-p-nitrophenyl-4, the synthetic preparation method with reference to I-b1-1 of 5-dihydro-isoxazole is synthetic, has obtained yellow solid I-b1-2, and yield is 90.0%, fusing point: 78-81 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.21(d，J＝9.0Hz，2H，Ar-H)，7.50(d，J＝8.4Hz，2H，Ar-H)，5.64(dd，J＝10.6，7.4Hz，1H，OCH)，3.50(dd，J＝16.7，10.9Hz，1H，CH
2)，2.89(dd，J＝16.8，7.2Hz，1H，CH
2)，1.21(s，9H，C(CH
3)
3).
The 3-tertiary butyl-5-p-amino phenyl-4, the synthetic preparation method with reference to I-b2-1 of 5-dihydro-isoxazole is synthetic, obtains yellow liquid I-b2-2, and yield is 93.2%.
1H?NMR(400MHz，CDCl
3)：δ7.11(d，J＝8.2Hz，2H，Ar-H)，6.66(d，J＝8.2Hz，2H，Ar-H)，5.42(t，J＝9.6Hz，1H，OCH)，3.68(brs，2H，NH
2)，3.30(dd，J＝16.8，10.5Hz，1H，CH
2)，2.90(dd，J＝16.8，8.6Hz，1H，CH
2)，1.22(s，9H，C(CH
3)
3).
The synthetic preparation method with reference to I-a-1 of target compound I-b-2 is synthetic, obtains white solid I-b-2 (0.75g), and yield is 85.2%, fusing point 266-268 ℃.
1H?NMR(400MHz，d6-DMSO)：δ11.47(brs，1H，CONHCO)，10.30(brs，1H，CONHAr)，7.52-7.74(m，5H，Ar-H)，7.36-7.49(m，2H，Ar-H)，7.14-7.31(m，4H，Ar-H)，5.71(t，J＝9.5Hz，1H，OCH)，3.83(dd，J＝17.1，10.8Hz，1H，CH
2)，3.36(dd，J＝17.1，8.5Hz，1H，CH
2).Anal.Calcd.for?C
23H
16F
3N
3O
3：C，62.87；H，3.67；N，9.56.Found：C，62.71；H，3.79；N，9.33.
Embodiment 3:I-c-1～I-c-3's is synthetic
The synthetic preparation of the method with reference to I-a1-1 of the 5-tertiary butyl-3-p-nitrophenyl isoxazole, obtains yellow solid I-c1-1, and yield is 30.9%, fusing point: 156-158 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.32(d，J＝8.7Hz，2H，Ar-H)，7.98(d，J＝8.7Hz，2H，Ar-H)，6.33(s，1H，Ar-H)，1.42(s，9H，C(CH
3)
3).
The synthetic preparation of the method with reference to I-b2-1 of the 5-tertiary butyl-3-p-aminophenyl isoxazole, obtains yellow solid I-c2-1, and yield is 96.0%, fusing point: 156-158 ℃.
1H?NMR(400MHz，CDCl
3)：δ7.59(d，J＝8.1Hz，2H，Ar-H)，6.71(d，J＝8.0Hz，2H，Ar-H)，6.15(s，1H，Ar-H)，3.84(brs，2H，NH
2)，1.37(s，9H，C(CH
3)
3).
The synthetic preparation method with reference to I-a-1 of target compound I-c-1 is synthetic, obtains white solid I-c-1, and yield is 85.4%, fusing point: 176-178 ℃.
1H?NMR(400MHz，CDCl
3)δ10.60(brs，1H，CONHCO)，9.93(brs，1H，CONHAr)，7.72(d，J＝8.4Hz，2H，Ar-H)，7.45-7.58(m，?3H，Ar-H)，7.05(t，J＝8.4Hz，2H，Ar-H)，6.23(s，1H，Ar-H)，1.40(s，9H，C(CH
3)
3).HRMS(ESI)m/z?calcd?for?C
21H
19F
2N
3O
3：(M+Na)
+422.1287，found?422.1296。
The synthetic preparation of the method with reference to I-c1-1 of 5-brooethyl-3-p-nitrophenyl isoxazole, obtains yellow solid, and yield is 53.9%, fusing point: 137-139 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.32-8.35(m，2H，Ar-H)，7.97-8.01(m，2H，Ar-H)，6.72(s，1H，Ar-H)，4.52(s，2H，CH
2Br).
In the dry there-necked flask of the synthetic 50mL of 5-trifluoroethoxy methyl-3-p-nitrophenyl isoxazole, add 0.072g sodium hydride, 20mL tetrahydrofuran (THF), adds 0.30g trifluoroethanol again under ice-water bath, stir 30 minutes.Then the THF solution that adds 0.51g 5-brooethyl-3-p-nitrophenyl isoxazole, is heated to back flow reaction.After having reacted (TLC detection), add water, ethyl acetate extraction, organic layer is successively with 5% dilute hydrochloric acid, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, revolve desolventizing, cross silicagel column, obtain yellow solid I-c1-2 (0.45g), yield is 81.8%.Fusing point: 73-75 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.28-8.40(m，2H，Ar-H)，7.95-8.05(m，2H，Ar-H)，6.72(s，1H，Ar-H)，4.86(s，2H，CH
2O)，4.00(q，J＝8.5Hz，2H，OCH
2CF
3).
The synthetic preparation of the method with reference to I-a2-1 of 5-trifluoroethoxy methyl-3-p-aminophenyl isoxazole, obtains yellow liquid I-c2-2, and yield is 92.7%.
1H?NMR(400MHz，CDCl
3)：δ7.61(d，J＝8.5Hz，2H，Ar-H)，6.74(d，J＝8.5Hz，2H，Ar-H)，6.54(s，1H，Ar-H)，4.79(s，2H，CH
2O)，3.95(q，J＝8.5Hz，2H，OCH
2CF
3)，3.93(brs，2H，NH
2).
The synthetic preparation method with reference to I-a-1 of target compound I-c-2 is synthetic, obtains white solid I-c-2, and yield is 85.4%, fusing point: 175-177 ℃.
1H?NMR(400MHz，CDCl
3)δ10.57(brs，1H，CONHCO)，8.18(brs，1H，CONHAr)，7.81(d，J＝8.5Hz，2H，Ar-H)，7.69(d，J＝8.5Hz，2H，Ar-H)，7.52-7.58(m，1H，Ar-H)，7.08(t，J＝8.6Hz，2H，Ar-H)，6.63(s，1H，Ar-H)，4.83(s，2H，CH
2O)，3.97(q，J＝8.5Hz，2H，OCH
2CF
3).Anal.Calcd.forC
20H
14F
5N
3O
4：C，52.76；H，3.10；N，9.23.Found：C，52.70；H，3.11；N，9.28.
The synthetic preparation of the method with reference to I-c1-2 of 5-fourth oxygen methyl-3-p-nitrophenyl isoxazole, obtains yellow viscous liquid I-c1-3, yield 78.2%.
1H?NMR(400MHz，CDCl
3)：δ8.28-8.38(m，2H，Ar-H)，7.94-8.06(m，2H，Ar-H)，6.65(s，1H，Ar-H)，4.66(d，J＝0.5Hz，2H，CH
2O)，3.59(t，J＝6.6Hz，2H，OCH
2CH
2)，1.53-1.69(m，2H，OCH
2CH
2CH
2)1.36-1.48(m，2H，CH
2CH
2CH
3)，0.94(t，J＝7.4Hz，3H，CH
2CH
3).
The synthetic preparation of the method with reference to I-a2-1 of 5-fourth oxygen methyl-3-p-aminophenyl isoxazole, obtains yellow liquid I-c2-3, and yield is 87.5%.
1H?NMR(400MHz，CDCl
3)：δ7.61(d，J＝8.5Hz，2H，Ar-H)，6.73(d，J＝8.5Hz，2H，Ar-H)，6.47(s，1H，Ar-H)，4.60(s，2H，CH
2O)，3.88(brs，2H，NH
2)，3.56(t，J＝6.6Hz，2H，OCH
2CH
2)，1.53-1.70(m，2H，OCH
2CH
2CH
2)，1.35-1.44(m，2H，CH
2CH
2CH
3)，0.93(t，J＝7.4Hz，3H，CH
2CH
3).
The synthetic preparation method with reference to I-a-1 of target compound I-c-3 is synthetic, obtains white solid I-c-3, and yield is 70.0%, fusing point: 156-158 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.60(brs，1H，CONHCO)，9.23(brs，1H，CONHAr)，7.77(d，J＝8.5Hz，2H，Ar-H)，7.50-7.67(m，3H，Ar-H)，7.06(t，J＝8.4Hz，2H，Ar-H)，6.56(s，1H，Ar-H)，4.64(s，2H，CH
2O)，3.58(t，J＝6.6Hz，2H，OCH
2CH
2)，1.53-1.70(m，2H，OCH
2CH
2CH
2)1.35-1.44(m，2H，CH
2CH
2CH
3)，0.94(t，J＝7.4Hz，3H，CH
2CH
3).HRMS(ESI)m/z?calcd?for?C
22H
21F
2N
3O
4：(M+Na)
+452.1392，found?452.1390.
Embodiment 4:I-a-15's is synthetic
5-brooethyl-3-p-nitrophenyl-4,5-dihydro-isoxazole synthetic: with reference to the method preparation of I-a1-1, obtain yellow solid I-a1-4, yield is 64.3%, fusing point: 161-163 ℃.
1HNMR(400MHz，CDCl
3)：δ8.28(d，J＝8.8Hz，2H，Ar-H)，7.85(d，J＝8.8Hz，Ar-H)，5.08-5.15(m，1H，OCH)，3.34-3.64(m，4H，CH
2).
Synthesizing of 2-oxygen-3-nitrogen-4-p-nitrophenyl-dicyclo [3.1.0]-3-hexene: in 50mL there-necked flask, add 0.44g I-a1-4,10mL DMF dissolves it, then adds 0.22g potassium tert.-butoxide, is heated to 80 ℃ of reactions 2 hours, and it is complete that TLC detects raw material reaction.Stopped reaction, cooling, add water, use dichloromethane extraction.Organic layer is successively with 5% dilute hydrochloric acid, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, revolve desolventizing, cross silicagel column, obtain yellow solid I-a1-15 (0.13g), yield is 65.0%, fusing point: 164-166 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.30(d，J＝8.6Hz，2H，Ar-H)，7.97(d，J＝8.6Hz，2H，Ar-H)，5.16(dd，J＝5.1，3.3Hz，1H，OCH)，2.87-2.97(m，1H，CHC＝N)，1.17(dt，J＝9.3，5.8Hz，1H，CH
2)，0.50(s，1H，CH
2).
Synthesizing of 2-oxygen-3-nitrogen-4-p-amino phenyl-dicyclo [3.1.0]-3-hexene: with reference to the method preparation of I-a2-1, obtain yellow liquid I-a2-15, yield is 84.6%.
1H?NMR(400MHz，CDCl
3)：δ7.60(d，J＝8.4Hz，2H，Ar-H)，6.70(d，J＝8.4Hz，2H，Ar-H)，4.97(dd，J＝5.0，3.2Hz，1H，OCH)，3.92(brs，2H，NH
2)，2.81-2.95(m，1H，CHC＝N)，1.00-1.05(m，1H，CH
2)，0.43(s，1H，CH
2).
Target compound I-a-15's is synthetic: the preparation method with reference to I-a-1 is synthetic, obtains white solid I-a-15, and yield is 81.8%, fusing point: 210 ℃ (decomposition).
1H?NMR(400MHz，CDCl
3)：δ10.56(brs，1H，CONHCO)，8.23(brs，1H，CONHAr)，7.79(d，J＝7.0Hz，2H，Ar-H)，7.64(d，J＝6.9Hz，2H，Ar-H)，7.52-7.59(m，1H，Ar-H)，7.08(t，J＝9.1Hz，2H，Ar-H)，5.05(dd，J＝5.3，3.3Hz，1H，OCH)，2.87-2.90(m，1H，CHC＝N)，1.08-1.12(m，1H，CH
2)，0.45-0.49(m，1H，CH
2).HRMS(ESI)m/z?calcd?for?C
18H
13F
2N
3O
3：(M+Na)
+380.0817，found?380.0820.
Embodiment 5:I-c-4's is synthetic
Synthesizing of 5-methyl-3-p-nitrophenyl isoxazole: in 100mL there-necked flask, add 0.07g NaH, 10mLTHF, adds 0.30g trifluoroethanol under ice-water bath is cooling, dropwises, and rises to room temperature.Add the THF solution of 0.57 gI-a1-4 again, rise to 50-60 ℃ of reaction 2 hours, it is complete that TLC detects raw material reaction.Stopped reaction, adds water, dichloromethane extraction.Organic layer is successively with 5% dilute hydrochloric acid, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, revolve desolventizing, cross silicagel column, obtain yellow solid I-c1-4 (0.32g), yield is 78.0%, fusing point: 153-155 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.31(d，J＝8.7Hz，2H，Ar-H)，7.97(d，J＝8.7Hz，2H，Ar-H)，6.38(s，1H，Ar-H)，2.53(s，3H，CH
3).
Synthesizing of 5-methyl-3-p-aminophenyl isoxazole: with reference to the method preparation of I-a2-1, obtain yellow liquid I-c2-4, yield is 95.8%.
1H?NMR(400MHz，CDCl
3)：δ7.59(d，J＝8.4Hz，2H，Ar-H)，6.72(d，J＝8.4Hz，2H，Ar-H)，6.20(s，1H，Ar-H)，3.87(brs，2H，NH
2)，2.44(s，3H，CH
3).
Target compound I-c-4's is synthetic: the preparation method with reference to I-a-1 is synthetic, obtains white solid I-c-4, and yield is 80.6%, fusing point: 213-216 ℃.
1H?NMR(400MHz，d6-DMSO)：δ11.50(brs，1H，CONHCO)，10.32(brs，1H，CONHAr)，7.61-7.82(m，5H，Ar-H)，7.26(t，J＝8.2Hz，2H，Ar-H)，6.74(s，1H，Ar-H)，2.44(s，9H，CH
3).Anal.Calcd.for?C
18H
13F
2N
3O
3：C，60.51；H，3.67；N，11.76.Found：C，60.59；H，3.48；N，11.62.
Embodiment 6:I-c-5's is synthetic
5-octyl group-3-p-nitrophenyl-4,5-dihydro-isoxazole synthetic: with reference to the method preparation of I-a1-1, obtain yellow solid I-a1-5, yield is 86.8%, fusing point: 74-76 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.26(d，J＝9.0Hz，2H，Ar-H)，7.83(d，J＝9.0Hz，Ar-H)，4.79-4.87(m，1H，OCH)，3.42(dd，J＝16.4，10.5Hz，1H，CH
2C＝N)，2.99(dd，J＝16.5，8.4Hz，1H，CH
2C＝N)，1.78-1.87(m，1H，OCHCH
2CH
2)，1.61-1.70(m，1H，OCHCH
2CH
2)，1.28-1.50(m，12H，CH
2(CH
2)
6CH
3)，0.88(t，J＝6.9Hz，3H，CH
2CH
3).
Synthesizing of 5-octyl group-3-p-nitrophenyl isoxazole: in 100mL four-hole mouth bottle, add 0.30g I-5a, 30mL tetracol phenixin, 0.196g N-bromo-succinimide (NBS), 0.05g Diisopropyl azodicarboxylate (AIBN), heating reflux reaction 5 hours.Add 10mL methyl alcohol, 0.16g sodium methylate, reflux to reaction finishes (TLC detection).Stopped reaction, adds water, ethyl acetate extraction.Organic layer is successively with 5% dilute hydrochloric acid, saturated common salt washing, anhydrous magnesium sulfate drying.Filter, revolve desolventizing, cross silicagel column, obtain yellow solid I-c1-5 (0.32g), yield is 66.7%, fusing point: 73-75 ℃.
1H?NMR(400MHz，CDCl
3)：δ8.31(d，J＝8.7Hz，2H，Ar-H)，7.98(d，J＝8.7Hz，2H，Ar-H)，6.37(s，1H，Ar-H)，2.82(t，J＝7.6Hz，2H，OCCH
2CH
2)，1.72-1.80(m，2H，OCCH
2CH
2CH
2)，1.28-1.41(m，10H，CH
2(CH
2)
5CH
3)，0.87(t，J＝6.5Hz，3H，CH
2CH
3).
Synthesizing of 5-octyl group-3-p-aminophenyl isoxazole: with reference to the method preparation of I-a2-1, obtain yellow liquid I-c2-5, yield is 83.3%.
1H?NMR(400MHz，CDCl
3)：δ7.60(d，J＝8.5Hz，2H，Ar-H)，6.72(d，J＝8.5Hz，2H，Ar-H)，6.19(s，1H，Ar-H)，3.85(brs，2H，NH
2)，2.75(t，?J＝7.6Hz，2H，OCCH
2CH
2)，1.68-1.76(m，2H，OCCH
2CH
2CH
2)，1.27-1.42(m，10H，CH
2(CH
2)
5CH
3)，0.88(t，J＝6.5Hz，3H，CH
2CH
3).
Target compound I-c-5's is synthetic: the preparation method with reference to I-a-1 is synthetic, obtains white solid I-c-5, and yield is 86.7%, fusing point: 169-171 ℃.
1H?NMR(400MHz，CDCl
3)：δ10.59(brs，1H，CONHCO)，9.29(brs，1H，CONHAr)，7.75(d，J＝8.5Hz，2H，Ar-H)，7.52-7.58(m，3H，Ar-H)，7.06(t，J＝8.5Hz，2H，Ar-H)，6.19(s，1H，Ar-H)，2.79(t，J＝7.5Hz，2H，OCCH
2CH
2)，1.71-1.78(m，2H，OCCH
2CH
2CH
2)，1.28-1.40(m，10H，CH
2(CH
2)
5CH
3)，0.88(t，J＝6.4Hz，3H，CH
2CH
3).Anal.Calcd.for?C
25H
27F
2N
3O
3：C，65.92；H，5.97；N，9.23.Found：C，65.74；H，5.81；N，9.29.
Embodiment 7: the mensuration of mythimna separate, mensuration program is as follows:
Oriental armyworm [Mythimna (=Pseudaletia) separata (Walker)] for examination insect, the normal population that indoor leaf of Semen Maydis is raised.Mythimna separata adopts leaf dipping method, sample is mixed with to the solution of different concns with acetone, and dipping Maize Seedling leaf, puts into 7cm culture dish after drying, and 10 of access 4 instar larvaes, repeat 2-4 time.Acetone soln soaking maize leaf breeding grub for contrast.After 24 hours, add at any time fresh maize leaf.24 hours, 48 hours, 72 hours, 96 hours viewing test results, until normally casting off a skin, control larvae became for 5 ages.Completely dead with armyworm larvae, touch motionless be the death standard of larva.Table 1 is the test result of compound.
Embodiment 8: kill the mensuration of mosquito larvae activity, mensuration program is as follows:
Northern house larva (Culex pipiens pallens) is tested insect.Adopt immersion method, every kind of medicine sample be mixed with to the solution of different concns with acetone solution, by 4 age mosquito larvae put into the aqueous solution of various samples, add micro-mosquito feed later every day, observe the blank situation of pupating, check result after 8d simultaneously.Each concentration repeats 4 times.Wherein acetone control group mortality ratio is 0%, take Ability of Culex Pipiens Larvae completely dead (the motionless death standard as larva touching), calculates cumulative correction mortality ratio.Table 1 is the test result of compound.
Embodiment 9: kill the mensuration of small cabbage moth activity, mensuration program is as follows:
The insect that small cabbage moth (Plutella xylostella) is raised with artificial diet for a long time for my chamber.Raising condition: T, 24-26 ℃; RH, 70%～80%; L/D, 14h/10h.When test, choose the Individual Size second instar larvae consistent with physiological status for examination.
The leaf dipping method that adopts international resistance Action Committee (IRAC) to propose.On analytical balance, take 2mg sample in 10mL small beaker, add 25 μ L dimethyl formamides (analytical pure) and dissolve, 1 Tween-20 emulsifying agent, adds 10mL water and makes 200ppm liquid, is diluted with water to desired concn.With straight peen ophthalmology tweezers dippings cabbage leaves, time 2-3 second, get rid of remaining liquid.Each a slice, 3, each sample, is successively placed in treatment paper by sample flag sequence.After liquid is dry, put into the long craspedodrome pipe of the markd 10cm of tool, access second instar larvae (culture dish of 60mm for beet armyworm, access beet exigua larvae in three ages) is built the mouth of pipe with gauze.Experiment is processed and is placed in standard chamber, check result after 3-4 days.Table 1 is the test result of compound.
Table 1 Compound I-1～I-15, II-1, II-2, III-1～III-15 and the HEXAFLUMURON inhibition activity to armyworm larvae, Ability of Culex Pipiens Larvae and diamondback moth larvae
Claims (4)
1. the benzoyl urea compound (I) containing isoxazoline structure,
It is characterized in that selecting the compound shown in following structure:
2. the preparation method of the benzoyl urea compound of Han isoxazoline structure claimed in claim 1, is characterized in that it comprises the steps:
Wherein R
4for hydrogen, R
5be respectively the tertiary butyl, to fluorophenyl.
3. the preparation method of the benzoyl urea compound of Han isoxazoline structure claimed in claim 1, is characterized in that it comprises the steps:
Wherein R
4be respectively the tertiary butyl, to fluorophenyl.
4. the application of the benzoyl urea compound of Han isoxazoline structure claimed in claim 1 on agricultural chemicals, is characterized in that it is as sterilant, control small cabbage moth.
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| CN105085326B (en) * | 2015-09-14 | 2017-04-19 | 天津农学院 | Benzoyl urea compound containing urethane group structure as well as preparation method and insecticidal application of benzoyl urea compound |
| CN106336395A (en) * | 2016-07-28 | 2017-01-18 | 浙江工业大学 | Benzamide derivatives containing urea bridge and preparation method and application thereof |
| WO2018191871A1 (en) * | 2017-04-18 | 2018-10-25 | 苏州大学张家港工业技术研究院 | Method for use in preparing isoxazoline derivative |
| CN107652246B (en) * | 2017-09-25 | 2020-08-25 | 江苏乾元生物科技有限公司 | Preparation method of 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole |
| CN107746392B (en) * | 2017-12-05 | 2020-10-09 | 河南师范大学 | Preparation method of oxazolidine compound containing bridged ring structure |
| CN114539180A (en) * | 2021-12-24 | 2022-05-27 | 贵州大学 | Isoxazoline-containing bisamide compound and preparation method and application thereof |
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| WO2003016293A1 (en) * | 2001-08-13 | 2003-02-27 | Bayer Cropscience Ag | Oxadiazolyl and thiadiazolyl benzoyl ureas and the use thereof as pesticides |
| CN1427828A (en) * | 2000-05-12 | 2003-07-02 | 拜尔公司 | Substituted N-benzoyl-N'-(tetrazolylphenyl)-ureas and their use as pest control agents |
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| WO2002076956A1 (en) * | 2001-03-23 | 2002-10-03 | Bayer Cropscience Gmbh | Arylisoxazoline derivatives, method for production and use thereof as pesticides |
| WO2003016293A1 (en) * | 2001-08-13 | 2003-02-27 | Bayer Cropscience Ag | Oxadiazolyl and thiadiazolyl benzoyl ureas and the use thereof as pesticides |
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