CN116283753A - Trifluoromethyl pyridine amide derivative and preparation method and application thereof - Google Patents
Trifluoromethyl pyridine amide derivative and preparation method and application thereof Download PDFInfo
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- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 230000000749 insecticidal effect Effects 0.000 claims abstract description 19
- 241000254173 Coleoptera Species 0.000 claims abstract description 11
- 241000255925 Diptera Species 0.000 claims abstract description 11
- 241000257303 Hymenoptera Species 0.000 claims abstract description 11
- 241000255777 Lepidoptera Species 0.000 claims abstract description 11
- 241000238814 Orthoptera Species 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims description 88
- 150000001875 compounds Chemical class 0.000 claims description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 239000011259 mixed solution Substances 0.000 claims description 38
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 32
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 28
- -1 trifluoromethylpyridine amide Chemical class 0.000 claims description 24
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 238000010438 heat treatment Methods 0.000 claims description 20
- 239000000575 pesticide Substances 0.000 claims description 20
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 16
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 14
- 239000002917 insecticide Substances 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 9
- OMRCXTBFBBWTDL-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=CC(Cl)=C1 OMRCXTBFBBWTDL-UHFFFAOYSA-N 0.000 claims description 8
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims description 7
- KJDIGQWBDQJIFR-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine-2-carboxamide Chemical class NC(=O)C1=NC=CC=C1C(F)(F)F KJDIGQWBDQJIFR-UHFFFAOYSA-N 0.000 claims description 5
- 239000012752 auxiliary agent Substances 0.000 claims description 5
- JZTVCHDVUWOXER-UHFFFAOYSA-N n-(trifluoromethyl)pyridine-2-carboxamide Chemical class FC(F)(F)NC(=O)C1=CC=CC=N1 JZTVCHDVUWOXER-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 238000001035 drying Methods 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 238000000967 suction filtration Methods 0.000 description 18
- 239000000375 suspending agent Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 238000001514 detection method Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 241000238631 Hexapoda Species 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000209094 Oryza Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 2
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 2
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 150000007945 N-acyl ureas Chemical class 0.000 description 2
- 241001556089 Nilaparvata lugens Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000005900 Flonicamid Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000500437 Plutella xylostella Species 0.000 description 1
- 239000005926 Pyridalyl Substances 0.000 description 1
- 239000005934 Sulfoxaflor Substances 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000004495 emulsifiable concentrate Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- RLQJEEJISHYWON-UHFFFAOYSA-N flonicamid Chemical compound FC(F)(F)C1=CC=NC=C1C(=O)NCC#N RLQJEEJISHYWON-UHFFFAOYSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- AEHJMNVBLRLZKK-UHFFFAOYSA-N pyridalyl Chemical group N1=CC(C(F)(F)F)=CC=C1OCCCOC1=C(Cl)C=C(OCC=C(Cl)Cl)C=C1Cl AEHJMNVBLRLZKK-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000003568 thioethers Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000004562 water dispersible granule Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- 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
- A01N47/40—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 a double or triple bond to nitrogen, e.g. cyanates, cyanamides
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Insects & Arthropods (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention provides a trifluoromethyl pyridine amide derivative, a preparation method and application thereof. The trifluoromethyl pyridine amide derivative provided by the invention has high insecticidal activity, and has good insecticidal effect on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects when the dosage in the medicament is very low.
Description
Technical Field
The invention belongs to the field of agricultural chemicals, and particularly relates to a trifluoromethyl pyridine amide derivative, a preparation method and application thereof.
Background
Pest control has been the core area of pesticide science research, and the wide use of pesticides has resulted in the effective control of a wide variety of pests. However, with the continuous expansion of the application scale of pesticides, the problem of drug resistance of the traditional pesticides is increasingly remarkable, and the traditional pesticides have higher toxicity, lower activity, larger usage amount and larger influence on environment, so that the research and development of green new pesticides become necessary choices.
In the creation of new green pesticides, fluorine-containing pesticides are a hotspot field of continuous research by people. Fluorine atoms have the properties of electronic effect, hydrogen-like simulation effect, blocking effect, fat-soluble permeation effect and the like, so that the fluorine atoms are widely applied to the fields of pharmaceutical chemistry, natural product chemistry, pesticide chemistry, fine chemicals and the like, the trifluoromethyl pyridine is taken as an important fluorine-containing heterocyclic structure, is a common group in the current preparation of pesticides, and the registered pesticides for controlling and killing insects comprise sulfoxaflor, flonicamid, pyridalyl and the like, and the pesticides containing the trifluoromethyl pyridine structure are subjected to research by people.
In recent years, the development is carried out around a trifluoromethyl pyridine structure, on the basis of the trifluoromethyl pyridine structure, an amide bond is adopted, a thioether structure is constructed, and the trifluoromethyl pyridine amide derivative containing an' -S=N-CN structure is designed and synthesized, so that the trifluoromethyl pyridine amide derivative has the remarkable characteristics of unique action mechanism, high efficiency, extremely low toxicity, environmental friendliness and the like, and is widely used.
According to the acyl thiourea or the acyl urea derivative containing the trifluoromethyl pyridine and the application thereof disclosed in the patent CN110526863B, the specific acyl thiourea or the acyl urea derivative containing the trifluoromethyl pyridine has an insecticidal effect on plutella xylostella and brown planthoppers, but the compound has a lethal activity of more than 75% on brown planthoppers when the mass concentration is 500mg/L, the dosage is large, and whether the compound has an insecticidal effect on other insects is not studied too much.
Therefore, there is a need for providing a trifluoromethylpyridine amide derivative which has a low dosage, a high lethal activity, and an insecticidal effect against insects of the orders lepidoptera, coleoptera, orthoptera, hymenoptera, and diptera.
Disclosure of Invention
The invention aims to provide a trifluoromethyl pyridine amide derivative, a preparation method and application thereof, and aims to solve the problems that the trifluoromethyl pyridine amide derivative in the prior art provided in the background art has large dosage and low lethal activity, and can not have insecticidal effects on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects at the same time.
In order to achieve the above purpose, the present invention provides the following technical solutions: in one aspect, the present invention provides a trifluoromethylpyridine amide derivative having a structure represented by formula i:
wherein R represents C 1 -C 3 Alkyl, hydroxyethyl, dimethylamino, 2-trifluoroethyl, pyridinyl or 1-fluorophenyl.
Further, the trifluoromethyl picolinamide derivative is selected from the group consisting of:
further, the trifluoromethyl picolinamide derivative is selected from the group consisting of:
further, in order to provide a better insecticidal effect to the trifluoromethylpyridine amide derivative, the trifluoromethylpyridine amide derivative is selected from the group consisting of compounds
In one aspect, the present invention provides a process for the preparation of a trifluoromethylpyridine amide derivative, comprising the steps of:
(1) Adding a mixed solution of 3-chloro-5-trifluoromethyl pyridine and a solvent I into a reactor, stirring, slowly dropwise adding a mixed solution of oxalyl chloride and dichloromethane, stirring at room temperature until the reaction is finished, and performing post-treatment to obtain an intermediate of a formula II-1;
(2) Adding concentrated ammonia water into a reactor, heating and stirring, slowly dropwise adding the mixed solution of the intermediate of the formula II-1 prepared in the step (1) and dichloromethane when the system temperature reaches 40-80 (for example, 40, 50, 60, 70 and 80), continuing stirring until the reaction is finished, and performing post-treatment to obtain the intermediate of the formula II-2;
(3) Adding the intermediate of the formula II-2 prepared in the step (2) and 1, 2-dichloroethane into a reactor, dropwise adding a mixed solution of oxalyl chloride and 1, 2-dichloroethane, heating to 30-70 (for example, 30, 40, 50, 60 and 70) DEG C after the dropwise adding is finished, and performing post-treatment after the reaction is finished to obtain a compound of the formula II;
(4) Adding lithium hydroxide, water and absolute ethyl alcohol into a reactor, stirring and dissolving, and then adding aminoethylthiol hydrochloride and R-CH 2 -Br, stirring at room temperature, and after finishing the reaction, obtaining an intermediate of the general formula III-1;
(5) Adding the intermediate of the general formula III-1 prepared in the step (4) and the anthranilic acid into a three-mouth bottle, adding 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of phosphorus oxychloride and 1, 2-dichloroethane, continuously heating to 40-60 ℃, and after the reaction is finished, performing post-treatment to obtain the intermediate of the general formula III-2;
(6) Adding the intermediate of the general formula III-2 prepared in the step (5) and cyanamide into a three-mouth bottle with a thermometer, adding a solvent II, stirring and dissolving, cooling to-10 < -2 > (for example, the temperature can be-10, -8, -6, -5, -4, -2) DEG C by using an ice salt bath, slowly dropwise adding iodobenzene diacetate, continuing stirring for 6-15h, and carrying out post-treatment to obtain a compound of the general formula III;
(7) Adding the compound of the formula II prepared in the step (3) and the solvent II into a reactor, stirring, slowly adding the compound of the general formula III prepared in the step (6), and carrying out post-treatment after the reaction is finished to obtain the trifluoromethyl pyridine amide derivative.
Further, the molar mass ratio of the compound of formula II to the compound of formula III is (1.05-1.15): 1.
further, the molar mass ratio of the 3-chloro-5-trifluoromethyl pyridine to the oxalyl chloride in the step (1) is 1: (1-1.3) (e.g., may be 1:1.1, 1:1.15, 1:1.2, 1:1.25, 1:1.3); the molar mass ratio of the intermediate II-1 in the step (2) to the concentrated ammonia water is 1: (4-5) (e.g., may be 1:4, 1:4.2, 1:4.4, 1:5); the molar mass ratio of the intermediate II-2 in the step (3) to oxalyl chloride is 1: (0.8-1.1) (e.g., may be 1:0.8, 1:0.9, 1:1, 1:1.1).
Further, the aminoethylthiooxide hydrochloride and R-CH in step (4) 2 -Br molar mass ratio (1-1.5): 1 (e.g., may be 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1); the molar mass ratio of the intermediate of the general formula III-1 to the anthranilic acid in the step (5) is 1:
(1.2-1.5) (e.g., may be 1:1.2, 1:1.3, 1:1.4, 1:1.5); the molar mass ratio of the intermediate of the general formula III-2 to the cyanamide in the step (6) is 1: (10-40) (e.g., may be 1:10, 1:15, 1:20, 1:24, 1:25, 1:28, 1:30, 1:35, 1:40).
Further, in the step (1), the first solvent is a mixed reagent of acetone and N, N-dimethylformamide.
Further, the second solvent in the step (6) and the step (7) is acetonitrile.
Further, the concentration of the concentrated aqueous ammonia in the step (2) is 25 to 28% (for example, 25%, 25.5%, 26%, 26.5%, 27%, 28%).
In another aspect, the invention provides the use of a trifluoromethylpyridine amide derivative in an insecticide.
Further, the insecticide is an insecticide for preventing and controlling lepidoptera, coleoptera, orthoptera, hymenoptera, diptera insects.
Further, when the trifluoromethylpyridinamide derivative is used as an active ingredient of an insecticide, the content in the insecticide is 0.05 to 99.9% (for example, may be 0.05%, 0.1%, 2%, 5%, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99.9% or any number therebetween), and in order to enhance the insecticidal effect of the trifluoromethylpyridinamide derivative as an active ingredient of an insecticide, it is preferable that the content of the trifluoromethylpyridinamide derivative in the insecticide is 10 to 80%.
Further, when the trifluoromethylpyridine amide derivative is used as an active ingredient of an insecticide, the content of the trifluoromethylpyridine amide derivative in the aqueous emulsion is 2 to 40% (for example, may be 2%, 5%, 10%, 12%, 17%, 20%, 26%, 30%, 35%, 40% or any value therebetween), preferably, the content of the trifluoromethylpyridine amide derivative in the aqueous emulsion is 10 to 30%; when the trifluoromethylpyridine amide derivative is used as an active ingredient of an insecticide, the content of the trifluoromethylpyridine amide derivative in the suspending agent is 3 to 60% of the active ingredient, preferably, the content of the trifluoromethylpyridine amide derivative in the suspending agent is 5 to 50%.
Further, the trifluoromethylpyridine amide derivative may be used alone; or the trifluoromethyl pyridine amide derivative is used as a main active ingredient and a pesticide auxiliary agent is used as a mode of the insecticidal composition, and can be processed into aqueous emulsion, suspending agent, water dispersible granule and emulsifiable concentrate, wherein the pesticide auxiliary agent is a common auxiliary agent in the field, and the common pesticide auxiliary agent comprises: a liquid carrier, such as water; organic solvents such as toluene, xylene, cyclohexanol, methanol, butanol, ethylene glycol, acetone, acetic acid, dimethyl sulfoxide, animal and vegetable oils, and fatty acids; commonly used surfactants such as emulsifiers and dispersants include anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, and the like.
Compared with the prior art, the invention has the beneficial effects that:
the trifluoromethyl pyridine amide derivative provided by the invention has high insecticidal activity, and has good insecticidal effect on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects when the dosage in the medicament is very low;
in addition, the "-S=N-CN" group contained in the trifluoromethyl pyridine amide derivative can be oxidized into CN-by the enzyme in the insect body, so that the respiratory enzyme in the insect body is inhibited, the insect respiratory poisoning death is caused, and the "-S=N-CN" group overcomes the defects of single target and narrow insecticidal spectrum of the existing insecticide.
Detailed Description
The invention will be described below in connection with specific embodiments. The following examples are illustrative of the present invention and are not intended to limit the present invention. Other combinations and various modifications within the spirit of the invention may be made without departing from the spirit or scope of the invention.
In the examples below, the monomers and reagents used are commercially available with the exception of the compounds of formula II-A, formula III-B, formula III-C, formula III-D, formula III-E, formula I-A, formula I-B, formula I-C, formula I-D, and formula I-E.
The preparation method of the compound of the formula I-A comprises the following steps:
(1) Adding a mixed solution of 2mol of 3-chloro-5-trifluoromethylpyridine, 5mol of acetone and 1mol of N, N-dimethylformamide into a reactor, stirring, slowly dropwise adding a mixed solution of 2.5mol of oxalyl chloride and 15mol of dichloromethane, stirring at room temperature until the reaction is finished, and spin-drying the system to obtain an intermediate of the formula II-1-A;
(2) Adding 16mol of concentrated ammonia water with the concentration of 25% into a reactor, heating and stirring, slowly dropwise adding 4mol of mixed solution of the intermediate of the formula II-1-A prepared in the step (1) and 20mol of dichloromethane when the temperature of the system reaches 60 ℃, continuously stirring until the reaction is finished, extracting the system by using 5mol of aqueous solution of NaOH with the concentration of 20% and 4mol of ethyl acetate, and spin-drying to obtain the intermediate of the formula II-2-A;
(3) Adding 4mol of the intermediate of the formula II-2-A prepared in the step (2) and 6mol of 1, 2-dichloroethane into a reactor, stirring at room temperature, dropwise adding 8mol of a mixed solution of oxalyl chloride and 3mol of 1, 2-dichloroethane, heating to 70 ℃ after the dropwise adding is finished, and obtaining a compound of the formula II-A after the reaction is finished for 0.5h and desolventizing;
wherein the stirring rate in the preparation of the compound of formula II-A is 100r/min;
(4) Adding 100mol of lithium hydroxide into another reactor, adding 10mol of water and 30mol of absolute ethyl alcohol, stirring and dissolving, then adding 3mol of aminoethylthiol hydrochloride and 2mol of p-fluorobenzyl bromide, stirring at room temperature, after TLC detection of the completion of the p-fluorobenzyl bromide reaction, removing most of the solvent, adding a mixed solution of 20mol of dichloromethane and 10mol of water for extraction, drying an organic phase by using anhydrous magnesium sulfate, filtering, and performing reduced pressure desolventizing under 0.1MPa to obtain an intermediate of a formula III-1-A;
(5) Adding 2mol of the intermediate of the formula III-1-A prepared in the step (4) and 2.4mol of anthranilic acid into a three-mouth bottle, adding 6mol of 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of 1.5mol of phosphorus oxychloride and 0.4mol of 1, 2-dichloroethane, continuously heating to 50 ℃, carrying out reaction, and after TLC quantitative detection, finishing the reaction when the residual intermediate of the formula III-1-A is less than 0.1%, using saturated NaHCO to the reaction solution 3 Stirring the solution, and carrying out suction filtration to obtain an intermediate of the formula III-2-A;
(6) Adding 2mol of the intermediate of the formula III-2-A prepared in the step (5) and 80mol of cyanamide into a three-mouth bottle with a thermometer, adding 20mol of acetonitrile, stirring and dissolving, slowly dropwise adding 400mol of iodobenzene diacetate when the temperature is reduced to minus 2 ℃, continuously stirring for 10 hours, quantitatively detecting that the reaction is finished when the residue of the intermediate of the formula III-2-A is less than 0.1% by TLC, spin-drying, and carrying out column chromatography by using 50mL of petroleum ether and 10mL of ethyl acetate to obtain a compound of the formula III-A;
(7) Adding 11.5mol of the compound of the formula II-A prepared in the step (3) and 15mol of acetonitrile into a reactor, stirring, slowly adding 10mol of the compound of the formula III-A prepared in the step (6), detecting that the compound of the formula II-A and the compound of the formula III-A are reacted by TLC, stopping the reaction, performing suction filtration to obtain a white solid, stirring and washing 500mL of normal hexane and 5mL of ethyl acetate, performing suction filtration, and continuing washing and suction filtration with 100mL of normal hexane to obtain the compound of the formula I-A; the analytical results of the compounds of the formula I-A are as follows:
1 HNMR(CDCl 3 8.74,8.36 (hydrogen on pyridine ring); 7.10,7.15,7.19,8.45,7.65 (hydrogen on benzene ring); 3.2,1.35 (methylene);
12 CNMR(CDCl 3 ,400MHz):41.8,48.6,129.8,135.5,162.9,147.3,147,139.7,132.8,125.0,137.2,131.9,115.5,115.2,131.6,131.9,115.5,132.3,124.4,123.6,148.8,164.9,170.3,116.6；
19 FNMR(CDCl 3 ,400MHz):-61.34,-95.40。
the preparation method of the compound of the formula I-B comprises the following steps:
(1) Adding a mixed solution of 2mol of 3-chloro-5-trifluoromethylpyridine, 5mol of acetone and 1mol of N, N-dimethylformamide into a reactor, stirring, slowly dropwise adding a mixed solution of 2.5mol of oxalyl chloride and 15mol of dichloromethane, stirring at room temperature until the reaction is finished, and spin-drying the system to obtain an intermediate of the formula II-1-A;
(2) Adding 16mol of concentrated ammonia water with the concentration of 25% into a reactor, heating and stirring, slowly dropwise adding 4mol of mixed solution of the intermediate of the formula II-1-A prepared in the step (1) and 20mol of dichloromethane when the temperature of the system reaches 60 ℃, continuously stirring until the reaction is finished, extracting the system by using 5mol of aqueous solution of NaOH with the concentration of 25% and 4mol of ethyl acetate, and spin-drying to obtain the intermediate of the formula II-2-A;
(3) Adding 4mol of the intermediate of the formula II-2-A prepared in the step (2) and 6mol of 1, 2-dichloroethane into a reactor, stirring at room temperature, dropwise adding 8mol of a mixed solution of oxalyl chloride and 3mol of 1, 2-dichloroethane, heating to 70 ℃ after the dropwise adding is finished, and obtaining a compound of the formula II-A after the reaction is finished for 0.5h and desolventizing;
wherein the stirring rate in the preparation of the compound of formula II-A is 100r/min;
(4) Adding 150mol of lithium hydroxide into another reactor, adding 8mol of water and 25mol of absolute ethyl alcohol, stirring and dissolving, then adding 2.16mol of aminoethylthiol hydrochloride and 1.8mol of 1-bromopropane, stirring at room temperature, after TLC detection of the reaction of 1-bromopropane is finished, removing most of solvent, adding a mixed solution of 15mol of dichloromethane and 8mol of water, extracting, drying an organic phase by using anhydrous magnesium sulfate, filtering, and performing reduced pressure desolventizing at-0.08 to obtain an intermediate of formula III-1-B;
(5) Adding 2.5mol of the intermediate of the formula III-1-B prepared in the step (4) and 3mol of anthranilic acid into a three-mouth bottle, adding 5mol of 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of 1.5mol of phosphorus oxychloride and 0.3mol of 1, 2-dichloroethane, continuously heating to 45 ℃ for reaction, and quantitatively detecting that the residue of the intermediate of the formula III-1-B is less than 0.1 by TLC% after the reaction, the reaction mixture was treated with saturated NaHCO 3 Stirring the solution, and carrying out suction filtration to obtain an intermediate of the formula III-2-B;
(6) Adding 2.5mol of the intermediate of the formula III-2-B prepared in the step (5) and 60mol of cyanamide into a three-mouth bottle with a thermometer, adding 23mol of acetonitrile, stirring and dissolving, slowly dropwise adding 450mol of iodobenzene diacetate when the temperature is reduced to minus 5 ℃, continuously stirring for 12 hours, quantitatively detecting that the residue of the intermediate of the formula III-2-B is less than 0.1 percent by TLC, completing the reaction, spin-drying, and carrying out column chromatography by using 60mL of petroleum ether and 10mL of ethyl acetate to obtain a compound of the formula III-B;
(7) Adding 22mol of the compound of the formula II-A prepared in the step (3) and 6mol of acetonitrile into a reactor, stirring, slowly adding 20mol of the compound of the formula III-B prepared in the step (6), detecting that the compound of the formula II-A and the compound of the formula III-B are reacted by TLC, stopping the reaction, performing suction filtration to obtain a white solid, stirring and washing 600mL of normal hexane and 5mL of ethyl acetate, performing suction filtration, and continuing washing and suction filtration with 50mL of normal hexane to obtain the compound of the formula I-B; the analytical results of the compounds of the formula I-B are as follows:
1 HNMR(CDCl 3 8.74,8.36 (hydrogen on pyridine ring); 7.19,8.45,7.65 (hydrogen on benzene ring); 3.2,1.35,1.09 (methylene); 0.80 (methyl);
12 CNMR(CDCl 3 ,400MHz):123.6，132.8,137.2,147.0,129.8,147.3,164.9,148.8，139.7,115.2,125.0,132.3,124.4,131.6,170.3,42.2,46.2,43.6,10.4,116.6；
19 FNMR(CDCl 3 ,400MHz):-61.34。
the preparation method of the compound of the formula I-C comprises the following steps:
(1) Adding a mixed solution of 2mol of 3-chloro-5-trifluoromethylpyridine, 5mol of acetone and 1mol of N, N-dimethylformamide into a reactor, stirring, slowly dropwise adding a mixed solution of 2.5mol of oxalyl chloride and 15mol of dichloromethane, stirring at room temperature until the reaction is finished, and spin-drying the system to obtain an intermediate of the formula II-1-A;
(2) Adding 16mol of concentrated ammonia water with the concentration of 25% into a reactor, heating and stirring, slowly dropwise adding 4mol of mixed solution of the intermediate of the formula II-1-A prepared in the step (1) and 20mol of dichloromethane when the temperature of the system reaches 60 ℃, continuously stirring until the reaction is finished, extracting the system by using 5mol of aqueous solution of NaOH with the concentration of 30% and 4mol of ethyl acetate, and spin-drying to obtain the intermediate of the formula II-2-A;
(3) Adding 4mol of the intermediate of the formula II-2-A prepared in the step (2) and 6mol of 1, 2-dichloroethane into a reactor, stirring at room temperature, dropwise adding 8mol of a mixed solution of oxalyl chloride and 3mol of 1, 2-dichloroethane, heating to 70 ℃ after the dropwise adding is finished, and obtaining a compound of the formula II-A after the reaction is finished for 0.5h and desolventizing;
wherein the stirring rate in the preparation of the compound of formula II-A is 100r/min;
(4) Adding 150mol of lithium hydroxide into another reactor, adding 15mol of water and 35mol of absolute ethyl alcohol, stirring and dissolving, then adding 3.5mol of aminoethylthiol hydrochloride and 2.5mol of 3-bromo-1-propanol, stirring at room temperature, after TLC detection of the reaction of 3-bromo-1-propanol is finished, removing most of solvent, adding a mixed solution of 30mol and 20mol of water, extracting, drying an organic phase by using anhydrous magnesium sulfate, filtering, and performing reduced pressure desolventizing under-0.07 MPa to obtain an intermediate of formula III-1-C;
(5) Adding 2.5mol of the intermediate of the formula III-1-C prepared in the step (4) and 3mol of anthranilic acid into a three-necked flask, adding 6.5mol of 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of 2mol of phosphorus oxychloride and 0.5mol of 1, 2-dichloroethane, continuously heating to 60 ℃, carrying out reaction, and after TLC quantitative detection, finishing the reaction when the residue of the intermediate of the formula III-1-C is less than 0.1%, using saturated NaHCO 3 Stirring the solution, and carrying out suction filtration to obtain a formula III-2-C intermediate;
(6) Adding 2.2mol of the intermediate of the formula III-2-C prepared in the step (5) and 88mol of cyanamide into a three-mouth bottle with a thermometer, adding 25mol of acetonitrile, stirring and dissolving, slowly dropwise adding 450mol of iodobenzene diacetate when the temperature is reduced to minus 2 ℃, continuously stirring for 10 hours, quantitatively detecting that the residue of the intermediate of the formula III-2-C is less than 0.1 percent by TLC, completing the reaction, spin-drying, and carrying out column chromatography by 70mL of petroleum ether and 10mL of ethyl acetate to obtain a compound of the formula III-C;
(7) Adding 16.5mol of the compound of the formula II-A prepared in the step (3) and 10mol of acetonitrile into a reactor, stirring, slowly adding 15mol of the compound of the formula III-C prepared in the step (6), detecting that the compound of the formula II-A and the compound of the formula III-C are reacted by TLC, stopping the reaction, performing suction filtration to obtain a white solid, stirring and washing 550mL of normal hexane and 5.5mL of ethyl acetate, performing suction filtration, and continuously washing and suction filtering 40mL of normal hexane to obtain the compound of the formula I-C; the analytical results of the compounds of the formula I-C are as follows:
1 HNMR(CDCl 3 8.74,8.36 (hydrogen on pyridine ring); 7.19,8.45,7.65 (hydrogen on benzene ring); 3.2,1.35,3.6 (methylene);
12 CNMR(CDCl 3 ,400MHz):123.6,132.8,137.2,147.0,129.8,147.3,164.9,148.8,139.7,115.2,125.0,132.3,124.4,131.6,170.3,42.2,42.5,83.5,116.6；
19 FNMR(CDCl 3 ,400MHz):-61.34。
the preparation method of the compound of the formula I-D comprises the following steps:
(1) Adding a mixed solution of 2mol of 3-chloro-5-trifluoromethylpyridine, 5mol of acetone and 1mol of N, N-dimethylformamide into a reactor, stirring, slowly dropwise adding a mixed solution of 2.5mol of oxalyl chloride and 15mol of dichloromethane, stirring at room temperature until the reaction is finished, and spin-drying the system to obtain an intermediate of the formula II-1-A;
(2) Adding 16mol of concentrated ammonia water with the concentration of 25% into a reactor, heating and stirring, slowly dropwise adding 4mol of mixed solution of the intermediate of the formula II-1-A prepared in the step (1) and 20mol of dichloromethane when the temperature of the system reaches 60 ℃, continuously stirring until the reaction is finished, extracting the system by using 5mol of aqueous solution of NaOH with the concentration of 20% and 4mol of ethyl acetate, and spin-drying to obtain the intermediate of the formula II-2-A;
(3) Adding 4mol of the intermediate of the formula II-2-A prepared in the step (2) and 6mol of 1, 2-dichloroethane into a reactor, stirring at room temperature, dropwise adding 8mol of a mixed solution of oxalyl chloride and 3mol of 1, 2-dichloroethane, heating to 70 ℃ after the dropwise adding is finished, and obtaining a compound of the formula II-A after the reaction is finished for 0.5h and desolventizing;
wherein the stirring rate in the preparation of the compound of formula II-A is 100r/min;
(4) Adding 120mol of lithium hydroxide into another reactor, adding 15mol of water and 20mol of absolute ethyl alcohol, stirring and dissolving, then adding 3.3mol of aminoethylthiol hydrochloride and 3mol of 1-bromo-3, 3-trifluoropropane, stirring at room temperature, after TLC detection of the reaction of 1-bromo-3, 3-trifluoropropane is finished, removing most of the solvent, adding a mixed solution of 20mol of dichloromethane and 10mol of water, extracting, drying an organic phase by using anhydrous magnesium sulfate, filtering, and performing reduced pressure desolventizing under 0MPa to obtain an intermediate of formula III-1-D;
(5) Adding 2.5mol of the intermediate of the formula III-1-D prepared in the step (4) and 3.5mol of anthranilic acid into a three-necked flask, adding 7.1mol of 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of 2.5mol of phosphorus oxychloride and 0.8mol of 1, 2-dichloroethane, continuously heating to 55 ℃, carrying out reaction, and quantitatively detecting that the residue of the intermediate of the formula III-1-D is less than 0.1% by TLC, and after the reaction is finished, using saturated NaHCO to carry out the reaction solution 3 Stirring the solution, and carrying out suction filtration to obtain an intermediate of the formula III-2-D;
(6) Adding 2.5mol of the intermediate of the formula III-2-D prepared in the step (5) and 70mol of cyanamide into a three-mouth bottle with a thermometer, adding 22mol of acetonitrile, stirring and dissolving, slowly dropwise adding 370mol of iodobenzene diacetate when the temperature is reduced to minus 5 ℃, continuously stirring for 12 hours, quantitatively detecting that the residue of the intermediate of the formula III-2-D is less than 0.1 percent by TLC, completing the reaction, spin-drying, and carrying out column chromatography by using 50mL of petroleum ether and 10mL of ethyl acetate to obtain a compound of the formula III-D;
(7) Adding 18.9mol of the compound of the formula II-A prepared in the step (3) and acetonitrile into a reactor, stirring, slowly adding 18mol of the compound of the formula III-D prepared in the step (6), detecting that the compound of the formula II-A and the compound of the formula III-D are reacted by TLC, stopping the reaction, performing suction filtration to obtain a white solid, stirring and washing 580 n-hexane and 5.8mL ethyl acetate, performing suction filtration, and continuously washing 60mL n-hexane, and performing suction filtration to obtain the compound of the formula I-D; the analytical results for the compounds of the formulae I-D are as follows:
1 HNMR(CDCl 3 8.74,8.36 (hydrogen on pyridine ring); 7.19,8.45,7.65 (hydrogen on benzene ring); 3.2,1.35,1.57 (methylene);
12 CNMR(CDCl 3 ,400MHz):123.6,132.8,137.2,147.0,129.8,147.3,164.9,148.8,139.7,115.2,125.0,132.3,124.4,131.6,170.3,42.2,46.2,61.0,110.4,116.6；
19 FNMR(CDCl 3 ,400MHz):-39.55,-61.34。
the preparation method of the compounds of the formulas I-E is as follows:
(1) Adding a mixed solution of 2mol of 3-chloro-5-trifluoromethylpyridine, 5mol of acetone and 1mol of N, N-dimethylformamide into a reactor, stirring, slowly dropwise adding a mixed solution of 2.5mol of oxalyl chloride and 15mol of dichloromethane, stirring at room temperature until the reaction is finished, and spin-drying the system to obtain an intermediate of the formula II-1-A;
(2) Adding 16mol of concentrated ammonia water with the concentration of 25% into a reactor, heating and stirring, slowly dropwise adding 4mol of mixed solution of the intermediate of the formula II-1-A prepared in the step (1) and 20mol of dichloromethane when the temperature of the system reaches 60 ℃, continuously stirring until the reaction is finished, extracting the system by using 5mol of aqueous solution of NaOH with the concentration of 25% and 4mol of ethyl acetate, and spin-drying to obtain the intermediate of the formula II-2-A;
(3) Adding 4mol of the intermediate of the formula II-2-A prepared in the step (2) and 6mol of 1, 2-dichloroethane into a reactor, stirring at room temperature, dropwise adding 8mol of a mixed solution of oxalyl chloride and 3mol of 1, 2-dichloroethane, heating to 70 ℃ after the dropwise adding is finished, and obtaining a compound of the formula II-A after the reaction is finished for 0.5h and desolventizing;
wherein the stirring rate in the preparation of the compound of formula II-A is 100r/min;
(4) 110mol of lithium hydroxide are added to a further reactor and dissolved by stirring with 12mol of water and 20mol of absolute ethanol, after which 3.3mol of aminoethylthiol hydrochloride and 3mol of the compound of the formula A are added
(5) 2.7mol of the intermediate of the formula III-1-E prepared in the step (4) and 3.24mol of anthranilic acid are added into a three-necked flask, 6.8mol of 1, 2-dichloroethane are added, stirred and dissolved, and then 2.8mol of phosphorus oxychloride is slowly added dropwiseAnd 0.8mol of 1, 2-dichloroethane, continuing to heat to 50 ℃ and then carrying out the reaction, and after TLC quantitative detection, the reaction is completed when the residue of the intermediate of the formula III-1-E is less than 0.1%, using saturated NaHCO to react the reaction solution 3 Stirring the solution, and carrying out suction filtration to obtain an intermediate of the formula III-2-E;
(6) Adding 2.8mol of the intermediate of the formula III-2-E prepared in the step (5) and 56mol of cyanamide into a three-mouth bottle with a thermometer, adding 20mol of acetonitrile, stirring and dissolving, slowly dropwise adding 415mol of iodobenzene diacetate when the temperature is reduced to minus 5 ℃, continuously stirring for 10 hours, quantitatively detecting that the residue of the intermediate of the formula III-2-E is less than 0.1 percent by TLC, completing the reaction, spin-drying, and carrying out column chromatography by using 60mL of petroleum ether and 10mL of ethyl acetate to obtain a compound of the formula III-E;
(7) Adding 13.2mL of the compound of the formula II-A prepared in the step (3) and 13mol of acetonitrile into a reactor, stirring, slowly adding 12mol of the compound of the formula III-E prepared in the step (6), detecting that the compound of the formula II-A and the compound of the formula III-E are reacted by TLC, stopping the reaction, performing suction filtration to obtain a white solid, stirring and washing 450mL of normal hexane and 4.5mL of ethyl acetate, performing suction filtration, and continuously washing and suction filtering 30mL of normal hexane to obtain the compound of the formula I-E; the analytical results for the compounds of formulae I-E are as follows:
1 HNMR(CDCl 3 8.74,8.36 (hydrogen on pyridine ring); 7.19,8.45,7.65 (hydrogen on benzene ring); 3.2,1.35,2.4 (methylene); 2.26,2.26 (methyl);
12 CNMR(CDCl 3 ,400MHz):123.6,132.8,137.2,147.0,129.8,147.3,164.9,148.8,139.7,115.2,125.0,132.3,124.4,131.6,170.3,41.9,44.2，81.6,46.0,116.6；
19 FNMR(CDCl 3 ,400MHz):-61.34。
mixing a compound of the formula I-A with a suspending agent and water to prepare a medicament of the embodiment 1, mixing a compound of the formula I-B with a suspending agent and water to prepare a medicament of the embodiment 2, mixing a compound of the formula I-C with a suspending agent and water to prepare a medicament of the embodiment 3, mixing a compound of the formula I-D with a suspending agent and water to prepare a medicament of the embodiment 4, mixing a compound of the formula I-E with a suspending agent and water to prepare a medicament of the embodiment 5, mixing a compound of the formula I-A, a compound of the formula I-B with a suspending agent and water to prepare a medicament of the embodiment 6 (at this time, the mass ratio of the compound of the formula I-A to the suspending agent in the medicament is 1:1), mixing a compound of the formula I-A, a suspending agent of the water to prepare a medicament of the embodiment 7 (at this time, the mass ratio of the compound of the formula I-A to the suspending agent in the medicament is 1:2), mixing a compound of the formula I-A to the suspending agent of the formula I-C to prepare a medicament of the embodiment 5, mixing a compound of the formula I-A with a suspending agent in the embodiment 8 (at this time, the mass ratio of the compound of the formula I-A to the suspending agent in the medicament of the embodiment 1:1, and mixing a compound of the formula I-A to prepare a compound of the formula I-C to prepare a medicament of the embodiment 9, and the compound of the formula I-A to prepare a medicament of the embodiment 1:1).
Wherein the concentrations of the medicaments prepared in examples 1 to 9 and comparative example 1 are 100 mug/mL and 50 mug/mL respectively (the concentrations of the medicaments are the contents of the compounds of the formula I and the chlorfenapyr in the medicaments in examples 1 to 9 and comparative example 1), wherein the mass ratio of the suspending agent and the water in the medicaments is 1:6, and the insecticidal effect of the medicaments with the concentrations of 100 mug/mL and 50 mug/mL on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects is tested by the following test method:
insecticidal activity test:
a: preparing medicines with the concentration of 100 mug/mL and 50 mug/mL respectively, soaking rice seedlings in the medicines for 10s, and airing for later use. And then 20 larvae of lepidoptera, coleoptera, orthoptera, hymenoptera and diptera (the larvae need to be starved for 5-6 hours) are respectively transferred to the rice seedlings immersed with the pesticide by using a transfer device, and finally the rice seedlings are placed in a pest-culturing room at 22+/-1 ℃ for constant temperature feeding, after 72 hours, the death number is counted, the death rate of the larvae is calculated (the larvae are touched by a writing brush and are regarded as death in no reaction), and the test results are shown in table 1 and table 2:
TABLE 1
TABLE 2
As can be seen from the comparison of the example 1 and the comparative example 1, when the concentration of the medicament is 100 mug/mL and 50 mug/mL respectively, the trifluoromethyl pyridine amide derivative provided by the invention has good insecticidal effect on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects, and the insecticidal effect of the medicament prepared by the trifluoromethyl pyridine amide derivative is better than that of the medicament prepared by chlorfenapyr;
as can be seen from comparison of examples 1 to 9, the trifluopicolinamide derivatives prepared by the different R groups have a death causing activity of more than 70% on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects, and the insecticidal effect of the pesticide prepared by the compound of formula I-a is better when the concentrations of the pesticide are the same;
in conclusion, the trifluoromethyl pyridine amide derivative provided by the invention has good insecticidal effects on lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects when the dosage in the medicament is very low.
The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the present invention and to implement it, but not limit the scope of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of the present invention.
Claims (8)
1. A trifluoromethylpyridine amide derivative characterized in that: the trifluoromethyl pyridine amide derivative has a structure shown in the following formula I:
wherein R represents C 1 -C 3 Alkyl, hydroxyethyl, dimethylamino, 2-trifluoroethyl, pyridinyl or 1-fluorophenyl.
2. A trifluoromethylpyridine amide derivative according to claim 1, characterized in that: the trifluoromethyl picolinamide derivative is selected from the group consisting of:
3. a trifluoromethylpyridine amide derivative according to claim 2, characterized in that: the trifluoromethyl picolinamide derivative is selected from the group consisting of:
4. a process for the preparation of a trifluoromethylpyridine amide derivative according to any one of claims 1 to 3, wherein: the method comprises the following steps:
(1) Adding 3-chloro-5-trifluoromethyl pyridine and a solvent I into a reactor, uniformly mixing, slowly dropwise adding a mixed solution of oxalyl chloride and dichloromethane, stirring at room temperature until the reaction is finished, and performing post-treatment to obtain an intermediate of a formula II-1;
(2) Adding concentrated ammonia water into a reactor, heating and stirring, slowly dropwise adding the mixed solution of the intermediate of the formula II-1 prepared in the step (1) and dichloromethane when the temperature of the system reaches 40-80 ℃, continuously stirring until the reaction is finished after the dropwise adding is finished, and performing post-treatment to obtain the intermediate of the formula II-2;
(3) Adding the intermediate of the formula II-2 prepared in the step (2), 1, 2-dichloroethane, dropwise adding a mixed solution of oxalyl chloride and 1, 2-dichloroethane into a reactor, heating to 30-70 ℃ after the dropwise adding is finished, and performing post-treatment to obtain a compound of the formula II;
(4) Adding lithium hydroxide, water and absolute ethyl alcohol into a reactor, stirring and dissolving, and then adding aminoethylthiol hydrochloride and R-CH 2 -Br, stirring at room temperature, and after finishing the reaction, obtaining an intermediate of the general formula III-1;
(5) Adding the intermediate of the general formula III-1 prepared in the step (4) and the anthranilic acid into a three-mouth bottle, adding 1, 2-dichloroethane, stirring and dissolving, slowly dropwise adding a mixed solution of phosphorus oxychloride and 1, 2-dichloroethane, continuously heating to 40-60 ℃, and after the reaction is finished, performing post-treatment to obtain the intermediate of the general formula III-2;
(6) Adding the intermediate of the general formula III-2 prepared in the step (5) and cyanamide into a three-mouth bottle with a thermometer, adding a solvent II, stirring and dissolving, cooling to-10 to-2 ℃ by using an ice salt bath, slowly dropwise adding iodobenzene diacetate, continuing stirring for 6-15h, and performing post-treatment to obtain a compound of the general formula III;
(7) Adding the compound of the formula II prepared in the step (3) and the solvent II into a reactor, stirring, slowly adding the compound of the general formula III prepared in the step (6), and carrying out post-treatment after the reaction is finished to obtain the trifluoromethyl pyridine amide derivative.
5. Use of a trifluoromethylpyridine amide derivative according to any one of claims 1 to 3 in an insecticide.
6. The use according to claim 5, characterized in that: the pesticide is used for preventing and controlling lepidoptera, coleoptera, orthoptera, hymenoptera and diptera insects.
7. The use according to claim 5, characterized in that: when the trifluoromethylpyridinamide derivative is used as an active ingredient of an insecticide, the content of the trifluoromethylpyridinamide derivative in the insecticide is 0.05 to 99.9%.
8. The use according to claim 5, characterized in that: the trifluoromethyl picolinamide derivative is used alone; or the trifluoromethyl pyridine amide derivative is used as a main active ingredient and a pesticide auxiliary agent is used as a mode of the insecticidal composition.
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