CN107382969B - Phenylpyrazole zwitterionic compound and application thereof in resistant pest control - Google Patents
Phenylpyrazole zwitterionic compound and application thereof in resistant pest control Download PDFInfo
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- CN107382969B CN107382969B CN201710610647.XA CN201710610647A CN107382969B CN 107382969 B CN107382969 B CN 107382969B CN 201710610647 A CN201710610647 A CN 201710610647A CN 107382969 B CN107382969 B CN 107382969B
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- phenylpyrazole
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- fipronil
- zwitterionic
- compound
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 82
- OEDUIFSDODUDRK-UHFFFAOYSA-N 5-phenyl-1h-pyrazole Chemical compound N1N=CC=C1C1=CC=CC=C1 OEDUIFSDODUDRK-UHFFFAOYSA-N 0.000 title claims abstract description 73
- 241000607479 Yersinia pestis Species 0.000 title claims abstract description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 54
- 238000002360 preparation method Methods 0.000 claims description 48
- ZOCSXAVNDGMNBV-UHFFFAOYSA-N 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile Chemical compound NC1=C(S(=O)C(F)(F)F)C(C#N)=NN1C1=C(Cl)C=C(C(F)(F)F)C=C1Cl ZOCSXAVNDGMNBV-UHFFFAOYSA-N 0.000 claims description 47
- 239000005899 Fipronil Substances 0.000 claims description 46
- 229940013764 fipronil Drugs 0.000 claims description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 27
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- -1 nitrogen-containing heterocyclic compound Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
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- 238000004519 manufacturing process Methods 0.000 claims 1
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- 102000005915 GABA Receptors Human genes 0.000 abstract description 7
- 108010005551 GABA Receptors Proteins 0.000 abstract description 7
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- 239000003208 petroleum Substances 0.000 description 17
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 239000013078 crystal Substances 0.000 description 16
- 241000256173 Aedes albopictus Species 0.000 description 15
- 238000001514 detection method Methods 0.000 description 15
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- 239000011734 sodium Substances 0.000 description 8
- 239000002917 insecticide Substances 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 241000257303 Hymenoptera Species 0.000 description 4
- 239000005906 Imidacloprid Substances 0.000 description 4
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- 229940056881 imidacloprid Drugs 0.000 description 4
- YWTYJOPNNQFBPC-UHFFFAOYSA-N imidacloprid Chemical compound [O-][N+](=O)\N=C1/NCCN1CC1=CC=C(Cl)N=C1 YWTYJOPNNQFBPC-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000575 pesticide Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
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- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 206010034133 Pathogen resistance Diseases 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
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- 244000045947 parasite Species 0.000 description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LMRKVKPRHROQRR-UHFFFAOYSA-N 4-butylmorpholine Chemical compound CCCCN1CCOCC1 LMRKVKPRHROQRR-UHFFFAOYSA-N 0.000 description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- AAYDMRDHPZEWIH-UHFFFAOYSA-N 4-fluoropyridazine Chemical compound FC1=CC=NN=C1 AAYDMRDHPZEWIH-UHFFFAOYSA-N 0.000 description 2
- NMILGIZTAZXMTM-UHFFFAOYSA-N 4-propylmorpholine Chemical compound CCCN1CCOCC1 NMILGIZTAZXMTM-UHFFFAOYSA-N 0.000 description 2
- CHODTZCXWXCALP-UHFFFAOYSA-N 5-bromoquinoline Chemical compound C1=CC=C2C(Br)=CC=CC2=N1 CHODTZCXWXCALP-UHFFFAOYSA-N 0.000 description 2
- HJSRGOVAIOPERP-UHFFFAOYSA-N 5-chloroquinoline Chemical compound C1=CC=C2C(Cl)=CC=CC2=N1 HJSRGOVAIOPERP-UHFFFAOYSA-N 0.000 description 2
- WMFXCDGQRHJFKL-UHFFFAOYSA-N 5-fluoroquinoline Chemical compound C1=CC=C2C(F)=CC=CC2=N1 WMFXCDGQRHJFKL-UHFFFAOYSA-N 0.000 description 2
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 2
- RNAAXKYOTPSFGV-UHFFFAOYSA-N 8-fluoroquinoline Chemical compound C1=CN=C2C(F)=CC=CC2=C1 RNAAXKYOTPSFGV-UHFFFAOYSA-N 0.000 description 2
- ZLKGGEBOALGXJZ-UHFFFAOYSA-N 8-methoxyquinoline Chemical compound C1=CN=C2C(OC)=CC=CC2=C1 ZLKGGEBOALGXJZ-UHFFFAOYSA-N 0.000 description 2
- 108010062745 Chloride Channels Proteins 0.000 description 2
- 102000011045 Chloride Channels Human genes 0.000 description 2
- 241001498622 Cixius wagneri Species 0.000 description 2
- 241000255925 Diptera Species 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 229960003540 oxyquinoline Drugs 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 2
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GWJXGGNBNZFXMM-UHFFFAOYSA-N 1,3-bis(phenylimino)thiourea Chemical compound C=1C=CC=CC=1N=NC(=S)N=NC1=CC=CC=C1 GWJXGGNBNZFXMM-UHFFFAOYSA-N 0.000 description 1
- HVQHXBNMBZJPLK-UHFFFAOYSA-N 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methylprop-2-en-1-yl)amino]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile Chemical compound CC(=C)CNC1=C([S+]([O-])C(F)(F)F)C(C#N)=NN1C1=C(Cl)C=C(C(F)(F)F)C=C1Cl HVQHXBNMBZJPLK-UHFFFAOYSA-N 0.000 description 1
- LWWDYSLFWMWORA-BEJOPBHTSA-N 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(E)-(4-hydroxy-3-methoxyphenyl)methylideneamino]-4-(trifluoromethylsulfanyl)pyrazole-3-carbonitrile Chemical compound c1cc(O)c(OC)cc1\C=N\c1c(SC(F)(F)F)c(C#N)nn1-c1c(Cl)cc(C(F)(F)F)cc1Cl LWWDYSLFWMWORA-BEJOPBHTSA-N 0.000 description 1
- XVPBINOPNYFXID-JARXUMMXSA-N 85u4c366qs Chemical compound C([C@@H]1CCC[N@+]2(CCC[C@H]3[C@@H]21)[O-])N1[C@@H]3CCCC1=O XVPBINOPNYFXID-JARXUMMXSA-N 0.000 description 1
- 241000254127 Bemisia tabaci Species 0.000 description 1
- 241001674044 Blattodea Species 0.000 description 1
- 241000426497 Chilo suppressalis Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241001414720 Cicadellidae Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- FNELVJVBIYMIMC-UHFFFAOYSA-N Ethiprole Chemical compound N1=C(C#N)C(S(=O)CC)=C(N)N1C1=C(Cl)C=C(C(F)(F)F)C=C1Cl FNELVJVBIYMIMC-UHFFFAOYSA-N 0.000 description 1
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 description 1
- 241001470017 Laodelphax striatella Species 0.000 description 1
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 description 1
- 241000257159 Musca domestica Species 0.000 description 1
- 241001556089 Nilaparvata lugens Species 0.000 description 1
- 241000500437 Plutella xylostella Species 0.000 description 1
- MWMQNVGAHVXSPE-UHFFFAOYSA-N Pyriprole Chemical compound ClC=1C=C(C(F)(F)F)C=C(Cl)C=1N1N=C(C#N)C(SC(F)F)=C1NCC1=CC=CC=N1 MWMQNVGAHVXSPE-UHFFFAOYSA-N 0.000 description 1
- 241000246044 Sophora flavescens Species 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 241000985245 Spodoptera litura Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241001481304 Vespoidea Species 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 238000001720 action spectrum Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- RFMQOHXWHFHOJF-UHFFFAOYSA-N cyano thiocyanate Chemical compound N#CSC#N RFMQOHXWHFHOJF-UHFFFAOYSA-N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
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- 230000002964 excitative effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229930014456 matrine Natural products 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229930015582 oxymatrine Natural products 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- DDIQWGKUSJOETH-UHFFFAOYSA-N pyrafluprole Chemical compound ClC=1C=C(C(F)(F)F)C=C(Cl)C=1N1N=C(C#N)C(SCF)=C1NCC1=CN=CC=N1 DDIQWGKUSJOETH-UHFFFAOYSA-N 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses a phenylpyrazole zwitterion compound and application thereof in resistant pest control. The phenylpyrazole zwitterionic compound belongs to a dipolar compound with positive and negative charges in a delocalized state, and molecules of the phenylpyrazole zwitterionic compound contain pharmacophore phenylpyrazole groups acting on gamma-aminobutyric acid receptors of insect nerve parts and zwitterionic groups of nicotinic acetylcholine receptors.
Description
Technical Field
The invention relates to a phenylpyrazole zwitterionic compound and application thereof in resistant pest control.
Background
Fipronil (fipronil), the first phenylpyrazole insecticide developed in 1989 by the company rona-planck, france, was first registered in our country in 1992. The target of the fipronil is GABA receptor in insect body, which mainly acts on synapse region of nerve terminal and muscle connection. Normally, GABA receptors in the insect body are activated and chloride channels in the binding sites for GABA action are opened correspondingly, resulting in chloride ion influx into the postsynaptic membrane of the nerve, promoting the polarization effect of action potential, and enabling the whole insect nervous system to operate in order. Fipronil interferes with the opening function of chloride ion channels, causes the local function of insect GABA receptors to be lost, the whole nerve center to be disordered, and the insects die due to body spasm and paralysis after reaching a certain dosage. Since the commercialization of fipronil in 1993, due to the irregular use and the cross resistance with a plurality of insecticides, a plurality of agricultural pests such as diamond back moth, small brown planthopper, rice planthopper, bemisia tabaci, prodenia litura and striped rice borer, and sanitary pests such as housefly, mosquito and cockroach have different resistance levels to fipronil. Also, with the widespread use of fipronil, its impact on the ecological safety is of great concern. A large number of researches show that fipronil has high toxicity to bees and silkworms, particularly causes serious harm to parasitic wasps in paddy fields, and also has high harm and high toxicity to aquatic organisms such as fishes. Therefore, the office of the Ministry of agriculture promulgates related documents, beginning 7.1.2009, which allowed the use of fipronil for hygiene and in part of dry land seed coatings, and in addition, the sale and popularization of other pesticide preparations containing fipronil ingredients must be prohibited in China.
In recent years, in order to reduce the resistance risk of fipronil, many fipronil derivatives have been developed in addition to butene-fipronil and ethiprole. In 2004, mitsubishi chemical reported three phenylpyrazole insecticides with higher activity than fipronil: pyrafluprole, pyriprole and vaniliprole. However, the toxicity of these phenylpyrazole insecticides to aquatic organisms, bees, silkworms and other beneficial organisms is not effectively solved due to their strong lipophilic nature.
Fischer and Bsohorn discovered a novel compound dehydrodithizone for the first time in 1882. In 1935 Earl and Mackney serendipitously discovered the zwitterionic compound sydnones and named it as city name local-sydnone, which was highly interesting to many scholars because it exhibited high insecticidal activity. A zwitterionic compound is finally defined as a dipolar compound with positive and negative charges in a delocalized state. Two new zwitterionic insecticides, triflumzopyrim and diclomezotiaz, developed by dupont in the united states have attracted considerable attention in recent years. The pesticide has the characteristics of wide action spectrum and high pesticide effect, is mainly used for preventing and treating piercing-sucking pests, particularly has good insecticidal effect on rice planthopper and leafhopper pests, and can also effectively prevent and treat the rice brown planthopper which generates resistance to imidacloprid. Triflumzopyrim is an insecticide acting on insect nACh receptors like imidacloprid and has a strong inhibitory effect on nerve excitation caused by acetylcholine, but triflumzopyrim specifically binds to insect nACh receptors at an orthosteric site and is different from neonicotinoid insecticides such as imidacloprid in a binding mode with a target site, and besides, the symptoms of the two insects are also different, imidacloprid causes the insects to die due to excitatory convulsion, and triflumzopyrim can directly cause the insects to die due to paralysis.
In order to reduce the toxicity of phenylpyrazole pesticides to beneficial organisms such as aquatic organisms, bees and silkworms, the applicant applied an invention patent of 'water-soluble benzopyrazoles quaternary ammonium salt and a preparation method and application thereof' in 2009, and obtained a patent with a patent authorization number of Z L200910040810 in 2011.
Disclosure of Invention
The invention aims to solve the technical problem of providing a phenylpyrazole zwitterion compound aiming at the defects of the existing matrine and oxymatrine extraction technology in sophora flavescens.
The invention also provides a preparation method of the phenylpyrazole zwitterionic compound.
The invention also aims to solve the technical problem of providing the application of the phenylpyrazole zwitterionic compound.
The purpose of the invention is realized by the following technical scheme:
provides a phenylpyrazole zwitterionic compound, the molecular structure of which is shown as the formula (I):
in formula (I):
comprises the following steps:
wherein R is4、R5、R6、R7、R8、R9And R10The same or different, are any of the following groups: hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, aralkyl, heteroaralkyl, halogen, nitro, amino, azido, alkoxy, hydroxyl, carboxyl, ester, ketone, ether, haloalkyl, haloamino, alkylamino, amido, sulfonyl, cyano, thioether, aldehyde, or epoxy.
The invention also provides application of the phenylpyrazole zwitterionic compound in preparing a medicinal preparation for preventing and treating resistant pests or sanitary pests in agriculture or animal and plant parasites.
The invention also provides a preparation method of the phenylpyrazole zwitterionic compound, which is characterized in that fipronil is used as a raw material, dimethylformamide is used as a solvent, anhydrous potassium carbonate is used as an acid-removing agent, and the phenylpyrazole zwitterionic compound is prepared at normal temperature.
Preferably, the molar ratio of the fipronil to the anhydrous potassium carbonate is 1: 1-2.5. Further preferably, the molar ratio of the fipronil to the anhydrous potassium carbonate is 1: 2.
The preparation method provided by the invention is more environment-friendly, the compound can be prepared at normal temperature, the addition amount of reactants not only accords with the general principle of chemical reaction for the optimal scheme of preparing the phenylpyrazole zwitterionic compound, but also provides the optimal guarantee for obtaining the phenylpyrazole zwitterionic compound. The method for purifying the compound can refer to the prior art in the field, but preferably, the invention adopts a recrystallization method to ensure that the optimal yield and the product purity are further obtained, and the condition parameters of recrystallization can refer to the prior art in the field.
Preferably, the preparation method of the phenylpyrazole zwitterionic compound comprises the following steps:
s1, dissolving fipronil in dimethylformamide, adding anhydrous potassium carbonate, dropwise adding bromoacetyl bromide, and stirring at normal temperature to react;
s2, adding a nitrogen-containing heterocyclic compound dissolved by dimethyl formamide into the system stirred and reacted in the step S1, and stirring at normal temperature until the reaction is complete;
and S3, quenching the system ice water after the reaction in the step S2 is completed, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering a filtrate, distilling under reduced pressure, performing column chromatography, and recrystallizing to obtain the phenylpyrazole zwitterion compound. Further preferably, the molar ratio of the fipronil to the bromoacetyl bromide to the nitrogen-containing heterocyclic compound to the anhydrous potassium carbonate is 1: 1-1.2: 1-2: 1-2.5.
More preferably, the molar ratio of the fipronil, the bromoacetyl bromide, the nitrogen-containing heterocyclic compound and the anhydrous potassium carbonate is 1:1.1:1.2: 2.
Preferably, the nitrogen-containing heterocyclic compound is quinoline, 5-aminoquinoline, N-dimethyl-5-aminoquinoline, 5-chloroquinoline, 5-bromoquinoline, 8-hydroxyquinoline, 8-methoxyquinoline, 5-fluoroquinoline, 4-methylquinoline, 8-fluoroquinoline, N-methylmorpholine, N-ethylmorpholine, N-propylmorpholine, N-butylmorpholine, pyridazine or 5-fluoropyridazine.
Preferably, the stirring reaction time of step S1 is 30 min.
Preferably, the reaction of step (a) with S2 is carried out overnight.
Preferably, the recrystallization in step S3 is recrystallization using methanol/petroleum ether.
The invention provides a phenylpyrazole zwitterionic compound prepared by the preparation method.
The phenylpyrazole zwitterionic compound prepared by the invention has good application in the aspects of preparing drug preparations for preventing and treating resistant pests or sanitary pests in agriculture or animal and plant parasites.
In particular when, in the formula (I),
is composed of
And meanwhile, the resistance times of the phenylpyrazole zwitter-ion compounds are less than 1, which shows that the resistant aedes albopictus screened by the fipronil becomes more sensitive to the four compounds and has negative cross resistance with the fipronil.
The invention has the beneficial effects that:
aiming at the prevention and control of resistant pests, the invention further performs breakthrough improvement on the basis of the existing research of the applicant, and prepares the phenylpyrazole zwitterion compound at normal temperature by adopting dimethyl formamide (DMF) as a solvent and anhydrous potassium carbonate as an acid-removing agent, and finds that the phenylpyrazole zwitterion compound shows obvious poisoning activity on the resistant pests when the zwitterion group is morpholine or substituted morpholine, pyridazine or substituted pyridazine and quinoline or substituted quinoline, thereby obtaining unexpected technical effects.
The invention provides a phenylpyrazole zwitterionic compound which has high efficiency, low toxicity to human and animals, low toxicity to shellfish aquatic organisms and bees, no serious damage to the environment, and easy degradation in water and soil, and can simultaneously act on insect gamma-aminobutyric acid receptors and nicotinic acetylcholine receptors so as to prepare a medicinal preparation for preventing and treating resistant pests or sanitary pests in agriculture or for preventing and treating animal and plant parasites, wherein the phenylpyrazole zwitterionic compound contains a delocalized mesoion active group structure, and the molecule contains a pharmacophore phenylpyrazole group of the gamma-aminobutyric acid receptors acting on insect nerve sites and a zwitterionic group of the nicotinic acetylcholine receptors, compared with a phenylpyrazole pesticide acting on the insect gamma-aminobutyric acid receptors alone, the phenylpyrazole zwitterionic compound simultaneously acts on two different target spots of the insect nerve sites, the compound has good activity, particularly has good control effect on resistant pests (such as the resistant aedes albopictus), can increase the pest control spectrum, and has very wide application prospect.
The environment-friendly preparation method selected by the invention has the advantages of easily available raw materials, mild reaction conditions, high yield and the like.
Detailed Description
The invention is further illustrated by the following specific examples. The following examples are for illustrative purposes only and are not to be construed as limiting the invention. Unless otherwise specified, the reagents used in the following examples are those conventionally commercially available or commercially available, and unless otherwise specified, the methods and apparatuses used in the following examples are those conventionally used in the art.
EXAMPLE 1 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method comprises the steps of adding 4.40g (0.01mol) of fipronil into a 100m L three-neck flask equipped with a magnetic stirrer, a drying tube and a dropping funnel, adding 40m L of dried DMF, stirring for dissolving, adding 2.76g (0.02mol) of anhydrous potassium carbonate, dropwise adding 1.78m L98% of bromoacetyl bromide, stirring for reaction at room temperature for 30min, adding 0.012mol of quinoline dissolved by DMF, stirring overnight at room temperature until the reaction is complete, quenching with ice water, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering a filtrate, distilling under reduced pressure, performing column chromatography, recrystallizing methanol/petroleum ether to obtain yellow crystals, wherein the yield is 62.40%, and the m.p.103-105 ℃ is detected as follows:
1H NMR(600MHz,DMSO)9.24(dd,J＝5.8,1.3Hz,1H,Ar-H),8.96(d,J＝8.3Hz,1H,Ar-H),8.23(d,J＝8.2Hz,1H,Ar-H),8.12–8.06(m,2H,Ar-H),7.95–7.87(m,2H,Ar-H),7.76(d,J＝1.4Hz,1H,quinoline),7.70(d,J＝1.4Hz,1H,quinoline),5.56(q,J＝16.6Hz,2H,CH2).
13C NMR(CDCl3,150MHZ):43.5,102.4,116.3,118.7,127.1,128.4,129.6,129.8,130.3,130.4,131.6,132.4,133.3,133.8,134.6,136.1,137.2,140.5,142.3,150.1,153.5,155.6,169.4；
HRMS(ESI-TOF):Extract mass calculated for C23H11Cl2F6N5O2S requires[M+H]+606.0032,found605.9987；[M+Na]+627.9860,found 627.9807。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 2 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein fipronil: bromoacetyl bromide: 5-aminoquinoline: the molar ratio of anhydrous potassium carbonate is 1:1.1:1.2: 1.8. Recrystallizing with methanol/petroleum ether to obtain red crystal with yield of 45.6% and m.p.258-265 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.11(d,J＝8.5Hz,1H),9.02–8.98(m,1H),7.87(d,J＝1.4Hz,1H,Ar-H),7.80(d,J＝1.5Hz,1H,Ar-H),7.70(t,J＝8.3Hz,1H),7.56(dd,J＝8.5,5.8Hz,1H),7.00(s,2H,NH2),6.97(d,J＝8.7Hz,1H),6.91(d,J＝8.0Hz,1H),5.30(dd,J＝35.7,16.3Hz,2H,CH2).
13C NMR(151MHz,DMSO)168.59,151.86,149.43,148.86,141.63,139.97,137.51,137.27,135.32,135.15,132.06,125.92,125.29,123.54,121.76,119.01,117.05,113.20,110.09,103.93,102.16,99.97,62.10.
HRMS(ESI-TOF):Extract mass calculated for C23H12Cl2F6N6O2S requires[M+H]+621.0109,found 621.0096；[M+Na]+642.9931,found 642.9916。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 3 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil, bromoacetyl bromide, N-dimethyl-5-aminoquinoline and anhydrous potassium carbonate is 1:1.2:1.3: 2.3. Recrystallizing with methanol/petroleum ether to obtain red crystal with yield of 15.52% and m.p.245-249 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.15(dd,J＝5.8,1.3Hz,1H),8.94(d,J＝8.5Hz,1H),7.93–7.89(m,1H),7.85(d,J＝1.4Hz,1H,Ar-H),7.80(d,J＝1.5Hz,1H,Ar-H),7.77(dd,J＝8.6,5.7Hz,1H),7.52(d,J＝8.9Hz,1H),7.34(d,J＝7.9Hz,1H),5.46(dd,J＝34.5,16.4Hz,2H,CH2),2.95(s,6H,CH3,CH3).
13C NMR(151MHz,DMSO)168.45,152.81,151.71,149.58,143.29,140.52,137.47,135.94,135.26,135.11,132.22,125.88,125.32,124.27,123.57,121.77,119.52,116.49,113.16,111.49,85.91,75.89,62.24,45.43.
HRMS(ESI-TOF):Extract mass calculated for C25H16Cl2F6N6O2S requires[M+H]+649.0389；found 649.0409。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 4 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 5-chloroquinoline to anhydrous potassium carbonate is 1:1.1:1.2: 2. Recrystallizing with methanol/petroleum ether to obtain yellow crystal with yield of 35.71% and m.p.158-166 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.39(dd,J＝5.8,1.1Hz,1H),9.09(d,J＝8.6Hz,1H),8.14(dd,J＝14.8,8.0Hz,2H),8.06(ddd,J＝12.9,8.8,6.7Hz,2H),7.80(d,J＝1.4Hz,1H,Ar-H),7.76(d,J＝1.4Hz,1H,Ar-H),5.65(q,J＝16.6Hz,2H,CH2).
13C NMR(151MHz,DMSO)168.07,151.34,151.20,142.73,140.09,137.32,135.42,135.20,135.07,132.50,130.39,127.88,126.91,125.73,125.61,125.39,123.51,122.89,121.69,119.54,113.09,102.34,62.31.
HRMS(ESI-TOF):Extract mass calculated for C23H10Cl3F6N5O2S requires[M+Na]+661.9446；found 661.9417。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 5 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 5-bromoquinoline to anhydrous potassium carbonate is 1:1.1:1.2: 2. Recrystallizing with methanol/petroleum ether to obtain yellow crystal with yield of 37.85% and m.p.174-180 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.39(dd,J＝5.8,1.1Hz,1H),9.09(d,J＝8.6Hz,1H),8.14(dd,J＝14.2,8.1Hz,2H),8.09–8.03(m,2H),7.80(d,J＝1.5Hz,1H,Ar-H),7.75(d,J＝1.6Hz,1H,Ar-H),5.65(q,J＝16.6Hz,2H,CH2).
13C NMR(151MHz,DMSO)167.58,150.84,150.69,142.24,139.59,136.82,134.92,134.70,134.57,132.00,131.76,129.89,127.37,126.41,125.25,124.89,123.01,122.38,121.19,119.03,112.59,101.84,61.81.
HRMS(ESI-TOF):Extract mass calculated for C23H10BrCl2F6N5O2S requires[M+Na]+705.8921；found 705.8912。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 6 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 8-hydroxyquinoline to anhydrous potassium carbonate is 1:1.2:1.5: 2.5. Recrystallizing with methanol/petroleum ether to obtain white crystal with yield of 55.03% and m.p.140-156 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)8.81(dd,J＝4.1,1.5Hz,1H),8.31(d,J＝8.3Hz,1H),8.04(s,1H,Ar-H),7.96(s,1H,Ar-H),7.54(dd,J＝8.3,4.2Hz,1H),7.46(d,J＝8.0Hz,1H),7.39(t,J＝7.9Hz,1H),6.95(d,J＝7.0Hz,1H),4.60(d,J＝25.5Hz,2H,CH2).
13C NMR(151MHz,DMSO)153.93,149.28,142.26,139.64,139.07,136.51,135.60,135.49,134.10,132.72,132.20,130.78,129.33,127.88,127.14,126.33,125.46,123.58,122.14,121.76,119.95,110.17,69.63.
HRMS(ESI-TOF):Extract mass calculated for C23H11Cl2F6N5O3S requires[M+H]+621.9945,found 621.9937。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 7 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 8-methoxyquinoline to anhydrous potassium carbonate is 1:1:1.2: 1. Recrystallizing with methanol/petroleum ether to obtain yellow crystal with yield of 15.70% and m.p.245-250 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.09(dd,J＝5.8,1.2Hz,1H),8.86–8.83(m,1H),7.87(dd,J＝8.3,5.8Hz,1H),7.82(t,J＝8.0Hz,1H),7.70(dd,J＝8.8,4.6Hz,2H,Ar-H),7.62(s,1H),7.58(d,J＝7.3Hz,1H),5.61(dd,J＝45.1,16.1Hz,2H,CH2),3.83(s,3H,OCH3).
13C NMR(151MHz,DMSO)169.48,151.81,151.61,151.39,146.94,137.50,135.00,134.92,131.96,131.74,131.37,130.98,130.30,127.95,125.74,125.38,123.53,122.17,121.74,116.59,113.27,101.84,67.53,57.49.HRMS(ESI-TOF):Extract mass calculatedfor C24H13Cl2F6N5O3S requires[M+H]+636.0094,found 636.0093。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 8 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 5-fluoroquinoline to anhydrous potassium carbonate is 1:1.1:2: 2.2. Recrystallizing with methanol/petroleum ether to obtain dark brown crystal with yield of 13.06%,
m.p.118-123 ℃. The detection data is as follows:
1H NMR(600MHz,DMSO)9.38(d,J＝5.8Hz,1H),8.99(d,J＝8.5Hz,1H),8.13–8.09(m,1H),8.04–7.98(m,2H),7.82–7.77(m,2H,Ar-H,Ar-H),7.75(d,J＝5.4Hz,1H),5.66–5.57(dd,2H,CH2).
13C NMR(151MHz,DMSO)167.99,158.58,156.46,151.38,151.34,137.28,135.99,135.93,135.08,134.98,131.25,131.11,125.74,125.33,123.70,122.20,120.05,119.41,116.44,114.06,113.08,103.72,62.20.
HRMS(ESI-TOF):Extract mass calculated for C23H10Cl2F7N5O2S requires[M+H]+623.9928,found 623.9893；[M+Na]+645.9744；found 645.9713。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 9 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 4-methylquinoline to anhydrous potassium carbonate is 1:1.2:1: 2. Recrystallizing with methanol/petroleum ether to obtain white crystal with yield of 60.21% and m.p.219-230 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.09(d,J＝6.0Hz,1H),8.33(d,J＝8.4Hz,1H),8.06(d,J＝3.5Hz,2H),7.93–7.89(m,1H),7.86(d,J＝1.4Hz,1H),7.79(dd,J＝6.0,0.7Hz,2H,Ar-H,Ar-H),5.50(q,J＝16.6Hz,2H),2.90(d,J＝16.2Hz,3H,CH3).
13C NMR(151MHz,DMSO)170.41,149.28,140.35,139.63,136.73,136.52,135.60,135.49,132.19,131.02,129.33,127.14,126.31,125.46,123.58,122.25,122.14,121.76,119.95,119.89,110.22,95.68,69.75,13.10.HRMS(ESI-TOF):Extract mass calculatedfor C24H13Cl2F6N5O2S requires[M+H]+620.0163,found 620.0144；[M+Na]+641.9985；found641.9963。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 10 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 8-fluoroquinoline to anhydrous potassium carbonate is 1:1:2: 2.5. Recrystallizing with methanol/petroleum ether to obtain yellow crystal with yield of 14.25% and m.p.160-178 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.29(dd,J＝5.8,1.1Hz,1H),9.01(d,J＝8.4Hz,1H),8.05(d,J＝8.0Hz,1H),8.00(dd,J＝8.4,5.8Hz,1H),7.96(ddd,J＝14.4,7.9,1.3Hz,1H),7.91(td,J＝8.0,4.3Hz,1H),7.73(d,J＝1.4Hz,1H,Ar-H),7.65(d,J＝1.3Hz,1H,Ar-H),5.60–5.51(m,2H,CH2).
13C NMR(151MHz,DMSO)172.48,168.63,153.34,152.22,151.65,151.36,147.06,137.32,134.96,134.85,131.13,130.55,130.49,129.28,126.98,125.79,125.40,123.49,122.51,121.68,121.53,113.19,65.87.
HRMS(ESI-TOF):Extract mass calculated for C23H10Cl2F7N5O2S requires[M+H]+623.9895,found 623.9893；[M+Na]+645.9720；found 645.9713。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 11 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to N-methylmorpholine to anhydrous potassium carbonate is 1:1.1:1.5: 1. Recrystallization from methanol/petroleum ether gave white crystals in 77.40% yield, m.p.205-213 ℃. The detection data is as follows:
1H NMR(600MHz,DMSO)8.22(d,J＝4.6Hz,2H,Ar-H),3.99(q,J＝15.4Hz,2H,morpholine),3.83–3.73(m,4H,morpholine),3.67–3.60(m,2H,morpholine),3.36(dd,J＝8.7,3.9Hz,2H,morpholine),3.15(s,3H,CH3).
13C NMR(151MHz,DMSO)166.79,151.59,138.01,135.69,135.57,132.90,132.67,127.94,126.66,125.67,125.59,123.58,121.77,113.17,103.07,65.64,60.12,59.45,47.28.
HRMS(ESI-TOF):Extract mass calculated for C19H15Cl2F6N5O3S requires[M+H]+578.0264,found 578.0250。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 12 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to N-ethylmorpholine to anhydrous potassium carbonate is 1:1.1:1.5: 1. Recrystallizing with methanol/petroleum ether to obtain white crystal with yield of 62.54% and m.p.146-156 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)8.25–8.21(m,2H,Ar-H,Ar-H),3.97(s,2H,CH2CH3),3.88–3.75(m,4H),3.69(t,J＝13.4Hz,2H),3.52(q,J＝7.1Hz,2H,CH2),3.31(s,2H),1.08(t,J＝7.2Hz,3H,CH2CH3).
13C NMR(151MHz,DMSO)166.84,151.75,138.09,135.78,135.65,133.15,132.92,132.70,132.47,130.21,127.99,126.58,125.68,123.62,121.84,113.05,103.16,59.95,58.09,7.39.
HRMS(ESI-TOF):Extract mass calculated for C20H17Cl2F6N5O3S requires[M+H]+592.0411,found 592.0406。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 13 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to N-propylmorpholine to anhydrous potassium carbonate is 1:1:1.6: 1.5. Recrystallizing with methanol/petroleum ether to obtain light pink crystal with yield of 73.50%, m.p.172-176 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)8.24(d,J＝2.4Hz,2H,Ar-H,Ar-H),3.98(s,2H),3.88–3.75(m,4H),3.68(dd,J＝28.0,13.8Hz,2H,CH2),3.42–3.35(m,4H),1.58–1.50(m,2H),0.74(t,J＝7.3Hz,3H,CH3).13C NMR(151MHz,DMSO)166.86,151.69,138.10,135.74,135.63,132.93,132.70,127.98,126.65,125.65,123.62,121.81,113.13,103.10,61.60,59.95,59.92,58.66,58.64,14.92,10.69.
HRMS(ESI-TOF):Extract mass calculated for C21H19Cl2F6N5O3S requires[M+H]+606.0566,found 606.0563。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 14 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to N-butylmorpholine to anhydrous potassium carbonate is 1:1.2:1.4: 2. Recrystallization from methanol/petroleum ether gave white crystals in 32.03% yield, m.p.178-192 ℃. The detection data is as follows:
1H NMR(600MHz,DMSO)8.25(d,J＝1.5Hz,2H,Ar-H,Ar-H),3.99(s,2H),3.89–3.75(m,4H),3.69(dd,J＝25.5,13.8Hz,2H,CH2),3.47–3.33(m,4H),1.54–1.47(m,2H),1.16–1.08(m,2H),0.83(dd,J＝9.7,5.0Hz,3H,CH3).
13C NMR(151MHz,DMSO)166.97,151.71,138.11,135.73,135.63,132.92,130.24,127.97,126.68,125.70,125.66,123.62,121.81,113.14,103.12,59.97,59.93,58.67,23.35,19.54,13.87.
HRMS(ESI-TOF):Extract mass calculated for C22H21Cl2F6N5O3S requires[M+Na]+642.0534,found 642.0539。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 15 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to pyridazine to anhydrous potassium carbonate is 1:1.1:2:2. Recrystallizing with methanol/petroleum ether to obtain pink crystal with yield of 81.10%, m.p.110-115 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.69(s,1H),9.43(s,1H),8.49(s,1H),8.35(s,1H),8.09(s,2H,Ar-H,Ar-H),5.44(d,J＝42.7Hz,2H,CH2).
13C NMR(151MHz,DMSO)172.46,170.81,167.51,153.84,150.99,136.37,135.43,135.37,127.73,127.62,126.48,125.47,123.57,121.75,112.88,60.20.
HRMS(ESI-TOF):Extract mass calculated for C18H8Cl2F6N6O2S requires[M+H]+554.9817,found 554.9805。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
EXAMPLE 16 preparation of zwitterionic Compounds of the phenylpyrazole type
The preparation method is the same as example 1, wherein the molar ratio of fipronil to bromoacetyl bromide to 5-fluoropyridazine to anhydrous potassium carbonate is 1:1.2:1.5: 1.3. Recrystallizing with methanol/petroleum ether to obtain pink crystal with yield of 81.10%, m.p.110-115 deg.C. The detection data is as follows:
1H NMR(600MHz,DMSO)9.79(s,1H),9.73(s,1H),7.98(s,1H),7.70(s,2H,Ar-H,Ar-H),6.04(d,2H,CH2).
13C NMR(151MHz,DMSO)200.10,187.20,155.80,150.17,144.30,142.23,135.47,135.37,131.43,128.89,126.23,123.60,123.60,123.15,122.76,121.20,114.40,59.20.
HRMS(ESI-TOF):Extract mass calculated for C18H8Cl2F6N6O2S requires[M+H]+574.9613,found 574.9611。
the molecular structure of the phenylpyrazole zwitterionic compound prepared in the embodiment is shown as the formula (I):
in formula (I):
comprises the following steps:
example 17 application test
The invention takes Aedes albopictus as an example to explain the application test effect, and for avoiding repeated description, the application test of other resistant pests is not described.
The biological activity of the aedes albopictus is measured by adopting a poisonous water feeding method to measure the poisoning activity of a compound on 3-year aedes albopictus larvae, a certain amount of the compound is prepared into mother liquor with a certain concentration by taking acetone as a solvent for standby, disposable plastic water cups are used, about 30m L of test solution (the solvent amount is less than 2%) in each cup, 10-15 larvae with the same size are inoculated by using gauze, the 3-year aedes albopictus larvae are placed in an insect breeding chamber with the temperature of 25 ℃ and the relative humidity of 60-70%, the number of dead insects is counted after 24h, 5 concentration gradients are set for each compound, each concentration is repeated for 3 times, fipronil is used as a medicament control, and acetone is used as a blank control.
Resistance screening of fipronil: when the majority of aedes albopictus bred in the colony is 2-3 years old, according to the biological activity determination result of the previous generation, a chemical liquid capable of killing 50-70% of fipronil in the colony is prepared, the mosquito is bred by using the test chemical liquid with the concentration, the breeding liquid is replaced by the same chemical liquid every day, 1000-plus 5000-head larvae are treated in each generation, 30-70% are eliminated, the surviving individuals are used as the insect seeds of the next generation, the generation-by-generation elimination selection is carried out, and the selection pressure is gradually increased. After raising for many generations, 3 instar larvae are taken for testing.
Determination of the biological activity of the resistant aedes albopictus: the method is the same as that of the sensitive Aedes albopictus.
L C of resistant strain and sensitive strain of Aedes albopictus of tenth generation50For comparison, the specific results of the fold resistance are shown in table 1, and the results show that: aedes albopictus developed 5.17 times resistance to fipronil, and the remaining 14 fold resistance of the phenylpyrazole zwitterionic compounds all showed low resistance or sensitivity, especially where the fold resistance of the compounds obtained in example 4, example 5, example 15 and example 11 was less than 1, 0.51,0.54,0.95 and 0.99, respectively, indicating that aedes albopictus resistant by fipronil screening became more sensitive to these four compounds, with negative cross-resistance to fipronil.
The compounds obtained in example 4, example 5, example 15 and example 11 were further analyzed by SPSS software for L C on the sensitive and resistant Aedes albopictus strains50The differences are shown in Table 2. The results show that both compounds obtained in example 4 and example 5 have a sig. in the t-test of < 0.05, indicating a significant difference in virulence for both sensitive and resistant aedes albopictus.
TABLE 1 fold resistance comparison of the resistant and sensitive strains of Aedes albopictus to Compounds
Watch 24Compound p-aedes albopictus L C50Differential analysis of
Claims (7)
1. The phenylpyrazole zwitterionic compound is characterized in that the molecular structure is shown as the formula (I):
(I)；
in formula (I):
comprises the following steps:
2. Use of the phenylpyrazole zwitterionic compounds according to claim 1 for the preparation of pharmaceutical preparations for controlling resistant pests in agriculture or resistant pests in hygiene.
3. The preparation method of the phenylpyrazole zwitterionic compound as claimed in claim 1, characterized in that fipronil is used as a raw material, dimethylformamide is used as a solvent, anhydrous potassium carbonate is used as an acid-removing agent, and the phenylpyrazole zwitterionic compound is prepared at normal temperature.
4. The preparation method of the phenylpyrazole-based zwitterionic compound according to claim 3, characterized in that the molar ratio of fipronil to anhydrous potassium carbonate is 1: 1-2.5.
5. The process for the preparation of zwitterionic compounds of the phenylpyrazole type according to claim 3 or 4, characterized in that it comprises the following steps:
s1, dissolving fipronil in dimethylformamide, adding anhydrous potassium carbonate, dropwise adding bromoacetyl bromide, and stirring at normal temperature to react;
s2, adding a nitrogen-containing heterocyclic compound dissolved by dimethyl formamide into the system stirred and reacted in the step S1, and stirring at normal temperature until the reaction is complete;
and S3, quenching the system ice water after the reaction in the step S2 is completed, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering a filtrate, distilling under reduced pressure, performing column chromatography, and recrystallizing to obtain the phenylpyrazole zwitterion compound.
6. The preparation method according to claim 5, wherein the molar ratio of fipronil to bromoacetyl bromide to the nitrogen-containing heterocyclic compound to anhydrous potassium carbonate is 1: 1-1.2: 1-2: 1-2.5.
7. The process for preparing a phenylpyrazole-based zwitterionic compound according to claim 5, characterized in that the stirring reaction time of step S1 is 30 min; the reaction time of step S2 is overnight.
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| US5556873A (en) * | 1993-02-24 | 1996-09-17 | Rhone-Poulenc Inc. | Pesticidal 1-aryl-5-(substituted alkyl (thio) amido)pyrazoles |
| CN101316509A (en) * | 2005-10-17 | 2008-12-03 | 伊萨罗里斯卡公司 | Compounds and relative use for the control of phytopathogens |
| CN101591295A (en) * | 2009-07-03 | 2009-12-02 | 华南农业大学 | Water-soluble benzopyrazoles class quaternary ammonium salt and its production and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5556873A (en) * | 1993-02-24 | 1996-09-17 | Rhone-Poulenc Inc. | Pesticidal 1-aryl-5-(substituted alkyl (thio) amido)pyrazoles |
| CN101316509A (en) * | 2005-10-17 | 2008-12-03 | 伊萨罗里斯卡公司 | Compounds and relative use for the control of phytopathogens |
| CN101591295A (en) * | 2009-07-03 | 2009-12-02 | 华南农业大学 | Water-soluble benzopyrazoles class quaternary ammonium salt and its production and application |
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