CN109384766B - Quinoline compound and preparation method and application thereof - Google Patents
Quinoline compound and preparation method and application thereof Download PDFInfo
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- CN109384766B CN109384766B CN201811379217.2A CN201811379217A CN109384766B CN 109384766 B CN109384766 B CN 109384766B CN 201811379217 A CN201811379217 A CN 201811379217A CN 109384766 B CN109384766 B CN 109384766B
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- isobutyl
- quinoline
- carbonate
- compound
- phenyl
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- -1 Quinoline compound Chemical class 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 241000123650 Botrytis cinerea Species 0.000 claims abstract description 8
- 241000223195 Fusarium graminearum Species 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
- 125000005059 halophenyl group Chemical group 0.000 claims abstract description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 18
- NKXUUVRXMYAZBL-UHFFFAOYSA-N 2-[[3-(2-methylpropyl)-4-(1H-pyrazol-5-yl)phenoxy]methyl]quinoline Chemical compound C(C(C)C)C=1C=C(OCC2=NC3=CC=CC=C3C=C2)C=CC=1C1=NNC=C1 NKXUUVRXMYAZBL-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 14
- 230000035484 reaction time Effects 0.000 claims description 14
- 229940073735 4-hydroxy acetophenone Drugs 0.000 claims description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 12
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- 150000003248 quinolines Chemical class 0.000 claims description 11
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 claims description 9
- YRNDGUSDBCARGC-UHFFFAOYSA-N 2-methoxyacetophenone Chemical compound COCC(=O)C1=CC=CC=C1 YRNDGUSDBCARGC-UHFFFAOYSA-N 0.000 claims description 9
- ZTQNUTNKGQGWCM-UHFFFAOYSA-N 2-methoxyquinoline Chemical compound C1=CC=CC2=NC(OC)=CC=C21 ZTQNUTNKGQGWCM-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 241000223221 Fusarium oxysporum Species 0.000 claims description 3
- 239000003495 polar organic solvent Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 150000005323 carbonate salts Chemical class 0.000 claims description 2
- 230000000855 fungicidal effect Effects 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims 3
- 241000223600 Alternaria Species 0.000 claims 1
- 239000000417 fungicide Substances 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 18
- 239000005730 Azoxystrobin Substances 0.000 abstract description 8
- WFDXOXNFNRHQEC-GHRIWEEISA-N azoxystrobin Chemical compound CO\C=C(\C(=O)OC)C1=CC=CC=C1OC1=CC(OC=2C(=CC=CC=2)C#N)=NC=N1 WFDXOXNFNRHQEC-GHRIWEEISA-N 0.000 abstract description 8
- 239000003899 bactericide agent Substances 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 244000309632 Alternaria arachidis Species 0.000 abstract description 4
- 244000000005 bacterial plant pathogen Species 0.000 abstract description 4
- 230000003385 bacteriostatic effect Effects 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 241000879841 Fusarium oxysporum f. cubense Species 0.000 abstract description 3
- 244000052616 bacterial pathogen Species 0.000 abstract description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 18
- 239000002904 solvent Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 229940126214 compound 3 Drugs 0.000 description 11
- 229940125898 compound 5 Drugs 0.000 description 11
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 10
- 239000007788 liquid Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000010791 quenching Methods 0.000 description 6
- 230000000171 quenching effect Effects 0.000 description 6
- 235000017060 Arachis glabrata Nutrition 0.000 description 5
- 244000105624 Arachis hypogaea Species 0.000 description 5
- 235000010777 Arachis hypogaea Nutrition 0.000 description 5
- 235000018262 Arachis monticola Nutrition 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 235000020232 peanut Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229920000742 Cotton Polymers 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000575 pesticide Substances 0.000 description 4
- LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 3
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 3
- 240000008067 Cucumis sativus Species 0.000 description 3
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 3
- 241000223218 Fusarium Species 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 241000209140 Triticum Species 0.000 description 3
- 235000021307 Triticum Nutrition 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HPJGEESDHAUUQR-SKGSPYGFSA-N (2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-1-[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-2-[[(2s)-3-naphthalen-2-yl-2-(3-pyridin-3-ylpropanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]buta Chemical compound NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)CCC=1C=NC=CC=1)CC1=CC=CC=C1 HPJGEESDHAUUQR-SKGSPYGFSA-N 0.000 description 2
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 2
- 244000058871 Echinochloa crus-galli Species 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229960004372 aripiprazole Drugs 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
- 229960001852 saquinavir Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- GSBZYMWABSULDI-APVIKVHPSA-N (3S,5R)-2-chloro-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound ClC1[C@H](C([C@@H](CC1(C(=O)O)O)O)O)O GSBZYMWABSULDI-APVIKVHPSA-N 0.000 description 1
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
- HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 1
- NNAYPIDFVQLEDK-UHFFFAOYSA-N 2-(bromomethyl)quinoline Chemical compound C1=CC=CC2=NC(CBr)=CC=C21 NNAYPIDFVQLEDK-UHFFFAOYSA-N 0.000 description 1
- CNULTLGKVRJBDK-UHFFFAOYSA-N 2-(fluoromethyl)quinoline Chemical group C1=CC=CC2=NC(CF)=CC=C21 CNULTLGKVRJBDK-UHFFFAOYSA-N 0.000 description 1
- IDPWXVBDDIYDKT-UHFFFAOYSA-N 2-phenoxyquinoline Chemical compound C=1C=C2C=CC=CC2=NC=1OC1=CC=CC=C1 IDPWXVBDDIYDKT-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- DZNTVPSDCWWMJR-UHFFFAOYSA-N formamide;1h-pyrazole Chemical compound NC=O.C=1C=NNC=1 DZNTVPSDCWWMJR-UHFFFAOYSA-N 0.000 description 1
- COYBRKAVBMYYSF-UHFFFAOYSA-N heptan-2-yl [(5-chloroquinolin-8-yl)oxy]acetate Chemical group C1=CN=C2C(OCC(=O)OC(C)CCCCC)=CC=C(Cl)C2=C1 COYBRKAVBMYYSF-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- HBEDNENASUYMPO-LJQANCHMSA-N n-hydroxy-4-[[(2r)-3-oxo-2-(thiophen-2-ylmethyl)-2,4-dihydroquinoxalin-1-yl]methyl]benzamide Chemical compound C1=CC(C(=O)NO)=CC=C1CN1C2=CC=CC=C2NC(=O)[C@H]1CC1=CC=CS1 HBEDNENASUYMPO-LJQANCHMSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a quinoline compound and a preparation method and application thereof. The structure of the compound is shown as a formula (I) or a formula (II), wherein R1Is one or more of H, hydroxyl, nitro, amino, halogen, phenyl or halophenyl. The compound has a novel structure, has a good bacteriostatic action, has a good inhibiting action on pathogenic bacteria of plant diseases, particularly has a good inhibiting action on botrytis cinerea, fusarium oxysporum f.sp.cubense, fusarium graminearum and alternaria arachidis hypogaea, and has a bacteriostatic action obviously superior to that of azoxystrobin; can be used as a bactericide for preventing and/or treating plant pathogenic bacteria, and the compound has wide application prospect in the field of prevention and/or treatment of plant diseases.
Description
Technical Field
The invention relates to the technical field of pesticide bactericides, and particularly relates to a quinoline compound and a preparation method and application thereof.
Background
Quinoline compounds are very important compounds in nitrogen-containing heterocycles. In the aspects of medical care and plant protection, a plurality of compounds containing quinoline ring structures show wide application and development prospects. In the aspect of medical care, quinoline medicines are widely used for preventing and treating diseases such as malaria, ulcer, cancer, HIV virus and schizophrenia. Quinine and chloroquine are early agents used in humans for the prevention and treatment of malaria and have been used to date. The recent related reports show that chloroquine also has a certain inhibition effect on SARS virus; saquinavir (saquinavir) was the first protease inhibitor marketed for the treatment of aids; aripiprazole (aripiprazole) is suitable for the treatment of various acute and chronic schizophrenia and schizoaffective disorders.
In the aspect of plant protection, the quinoline compounds also show high-efficiency bactericides and herbicides. Phenoxyquinoline is a very effective powdery mildew inhibitor; the cloquintocet-mexyl is a chloroquinate herbicide, can thoroughly prevent and kill barnyard grass in a rice field, is effective to senile barnyard grass, has low dosage as a herbicide for the rice field, is convenient to apply, and is safe to direct seeding and transplanting rice. As a pesticide research, the quinoline compound develops a new world for the development of pesticide chemistry and provides a new way for searching novel pesticides with high efficiency and low toxicity.
Introduction of other active groups into quinoline skeleton is a common method for researching new quinoline derivative bactericides, and for example, 1,2,3, 4-tetrahydroquinoline is combined with pyrazole formamide to prepare a compound with bactericidal activity reported in patent CN 201510796235.0. But the bactericidal activity and bactericidal spectrum of the quinoline derivative still have wide research prospects.
Disclosure of Invention
The invention aims to provide a quinoline compound. According to the invention, the quinoline compound with a novel structure is prepared by modifying benzyloxy with a pyrazole substituent in a quinoline structure, and the compound has a good antibacterial effect, has a good inhibitory effect on pathogenic bacteria of plant diseases, especially on botrytis cinerea, fusarium oxysporum f.sp.cubense, fusarium graminearum and peanut brown spot bacteria, and has an antibacterial effect obviously superior to that of azoxystrobin; the compound can be used as a bactericide for preventing and/or treating plant diseases.
The invention also aims to provide a preparation method of the quinoline compound.
The invention further aims to provide application of the quinoline compound in preventing and/or treating plant diseases.
The above object of the present invention is achieved by the following scheme:
a quinoline compound has a structure shown in a formula (I) or a formula (II):
wherein R is1Is one or more of hydroxyl, nitro, amino, halogen, phenyl or halogenated phenyl.
Preferably, said R is1Is one of bromine, iodine, phenyl or halophenyl.
Preferably, said R is1Is 3-fluoro, 4-fluoro, 3-chloro, 4-chloro or phenyl.
Preferably, said R is1Is 3-chloro, 4-fluoro or 4-phenyl.
The invention also provides a preparation method of the quinoline compound, which comprises the following steps:
s1, synthesizing 2-isobutyl-4-hydroxyacetophenone by using 2-isobutyl-4-methoxyacetophenone as a raw material; dissolving 2-isobutyl-4-hydroxyacetophenone, 2-halomethylquinoline and carbonate in an organic solvent for reaction to prepare 2-isobutyl-4- (2-quinoline) methoxyacetophenone;
s2, mixing and reacting 2-isobutyl-4- (2-quinoline) methoxyacetophenone, DMF and DMA to obtain (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one; then dissolving the 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline in a polar solvent to react with hydrazine to prepare 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline;
s3, finally, 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline and R1The substituted benzyl bromide compound and carbonate are dissolved in an organic solvent to react to prepare the target product.
Preferably, the molar ratio of the 2-isobutyl-4-hydroxyacetophenone, the 2-halomethylquinoline and the carbonate in step S1 is 1: 1.1-1.5: 0.2-0.5; the organic solvent is DMF, and the carbonate is potassium carbonate, sodium carbonate or cesium carbonate; the reaction temperature is 50-60 ℃, and the reaction time is 8-14 h.
More preferably, the 2-halomethylquinoline is 2-fluoromethylquinoline, 2-chloromethylquinoline, 2-bromomethylquinoline in step S1; further preferred is 2-chloromethylquinoline.
More preferably, the molar ratio of 2-isobutyl-4-hydroxyacetophenone, 2-chloromethyl quinoline and carbonate in step S1 is 1: 1.1: 0.5; the carbonate is cesium carbonate; the reaction temperature is 60 ℃, and the reaction time is 12 h.
Preferably, the preparation process of the 2-isobutyl-4-hydroxyacetophenone in the step S1 is as follows: dissolving 2-isobutyl-4-methoxyacetophenone in an organic solvent, keeping the temperature at 0 ℃, then dropwise adding boron tribromide, and reacting at room temperature to obtain the 2-isobutyl-4-hydroxyacetophenone.
More preferably, the molar ratio of 2-isobutyl-4-methoxyacetophenone to boron tribromide is 48: 0.5; wherein the organic solvent is dichloromethane; the reaction time was 12 h.
In the step S2, the molar ratio of (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one to hydrazine is 1: 0.5-1; the polar organic solvent is ethanol; the reaction conditions are heated and refluxed; the reaction time is 6-12 h;
more preferably, the hydrazine in step S2 is hydrazine hydrochloride; the molar ratio of the (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one to the hydrazine is 1: 0.5; the reaction time was 12 h.
Preferably, the reaction temperature for preparing (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one in step S2 is 100 ℃ and the reaction time is 12 h.
2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline, R in step S31The molar ratio of the substituted benzyl bromide compound to the carbonate is 1: 1.2-2.0: 1.4-3; the organic solvent is DMF, DMA or DMSO, and the carbonate is potassium carbonate, sodium carbonate or cesium carbonate; the reaction temperature is 40-60 ℃, and the reaction time is 8-14 h.
More preferably, 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline, R in step S31The molar ratio of substituted benzyl bromide compound to carbonate salt is 1: 1.67: 2; the organic solvent is DMF, and the carbonate is cesium carbonate; the reaction temperature is 50 ℃, and the reaction time is 12 h.
The application of the quinoline compound in preventing and/or treating plant diseases is also within the protection scope of the invention.
More preferably, the application is the application of preventing and/or treating botrytis cinerea, fusarium oxysporum, fusarium graminearum and alternaria arachidis.
The invention also protects the application of the quinoline compound in preparing bactericide.
Compared with the prior art, the invention has the following beneficial effects:
the compound has a novel structure, has a good bacteriostatic action, has a good inhibiting action on pathogenic bacteria of plant diseases, particularly has a good inhibiting action on botrytis cinerea, fusarium oxysporum f.sp.cubense, fusarium graminearum and alternaria arachidis hypogaea, and has a bacteriostatic action obviously superior to that of azoxystrobin; can be used as a bactericide for preventing and/or treating plant pathogenic bacteria, and the compound has wide application prospect in the field of prevention and/or treatment of plant diseases.
Detailed Description
The present invention is further described in detail below with reference to specific examples, which are provided for illustration only and are not intended to limit the scope of the present invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
The instruments and reagents used in the following examples were:
1h NMR Using a Bruker Furier 300MHz NMR spectrometer, CD3OD is a solvent, and TMS is an internal standard substance; LC-MS used Agilent 6100; HPLC was performed using Agilent 1260.
The reagents used are all commercially available analytical reagents unless otherwise specified.
The preparation of the compounds in the following examples is schematically as follows:
EXAMPLE 1 preparation of Compounds 7c and 8c
Compound 7 c: 2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline;
compound 8 c: 2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline.
The structures of compounds 7c and 8c are shown below:
the preparation process comprises the following steps:
(1) preparation of 2-isobutyl-4-hydroxyacetophenone (Compound 2): 10g (48mmol) of 2-isobutyl-4-methoxyacetophenone (compound 1) and 100mL of dichloromethane were added to a reaction flask, cooled to 0 ℃ and 45mL (0.5mol) of boron tribromide was added dropwise. The reaction was stirred at room temperature for 12h and TLC showed completion of the reaction. After quenching with water, dichloromethane was added for extraction (100 mL. times.3), the organic phase was collected, dried over anhydrous sodium sulfate and concentrated to give 8.8g of 2 (i.e.) 2-isobutyl-4-hydroxyacetophenone as a colorless oily liquid with a yield of 96%. LC-MS, m/z: 193.2[ M + H ] +.
(2) Preparation of 2-isobutyl-4- (2-quinoline) methoxyacetophenone (compound 3): into a reaction flask were successively charged 8.8g (46mmol) of Compound 2, 9.1g (51mmol) of 2-chloromethylquinoline, 7.5g (23mmol) of cesium carbonate and 100ml of DMF. The reaction was stirred at 50 ℃ for 12 h. TLC showed the reaction was complete. After the solvent was removed, the crude product was concentrated, and 11.7g of colorless oily liquid compound 3 was obtained by column chromatography separation, with a yield of 76%. LC-MS, m/z: 334.2[ M + H ] +.
(3) Preparation of (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one (Compound 4): 11.7g (35mmol) of Compound 3 and 200mL of DMF/DMA were added sequentially to the reaction flask and the reaction was stirred at 100 ℃ for 12 h. TLC showed the reaction was complete. The solvent was removed and the crude product was concentrated and separated by column chromatography to give 9.5g of colorless oily liquid compound 4 with a yield of 70%. LC-MS, m/z: 389.1[ M + H ] +.
(4) Preparation of 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline (compound 5): 9.5g (24.5mmol) of Compound 4, 12.9g (12.3mmol) of hydrazine hydrochloride, and 120mL of ethanol were sequentially added to the reaction flask, and the reaction was refluxed for 12 hours. TLC showed the reaction was complete. Quenching reaction, removing solvent, concentrating to obtain crude product, and separating by column chromatography to obtain 7.3g white solid compound 5 with yield of 84%. LC-MS, m/z: 358.2[ M + H ] +.
(5) Preparation of 2- (3-isobutyl-4- (1- ((2-trifluoromethoxy) benzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline (7c) and 2- (3-isobutyl-4- (1- ((2-trifluoromethoxy) benzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline (8 c): 214mg (0.6mmol) of Compound 5, 255mg (1.0mmol) of 3-chlorobenzyl bromide (Compound 6), 391mg (1.2mmol) of cesium carbonate and 10mL of DMF were sequentially added to a 30mL reaction flask, heated to 50 ℃ and reacted for 12h, TLC indicated completion of the reaction. After removal of the solvent, dichloromethane was added for extraction (20 mL. times.3), the organic phase was collected, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product.
HPLC was used to prepare 2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline (7c) in 17% yield and 2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline (8c) in 7% yield.
2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline (7c) with a yield of 17%. 1H NMR (CD3OD,300MHz), δ:9.22(d, J ═ 8.6Hz,1H),8.47-8.34(m,2H), 8.30-8.17 (m,2H),8.01(t, J ═ 7.6Hz,1H), 7.93-7.87 (m,1H), 7.47-7.04 (m,7H),6.48(t, J ═ 2.2Hz,1H),5.78(s,2H),5.43(s,2H),2.67(d, J ═ 7.2Hz,2H), 1.71-1.58 (m,1H),0.71(d, J ═ 6.6Hz, 6H); LC-MS, M/z 481.9[ M + H ] +, tR 2.03 min; HPLC, 97% (214nm), 98% (254nm), tR 7.98min.
2- (3-isobutyl-4- (1- (3-chlorobenzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline (8c) with a yield of 7%. 1H NMR (CD3OD,300MHz), δ:9.23(d, J ═ 8.7Hz,1H),8.40(t, J ═ 8.9Hz,2H),8.27 to 8.18(m,2H),8.01(t, J ═ 7.6Hz,1H),7.74(d, J ═ 2.0Hz,1H),7.28 to 7.07(m,5H),6.91 to 6.83(m,2H),6.39(d, J ═ 2.0Hz,1H),5.80(s,2H),5.16(s,2H),2.22(d, J ═ 7.2Hz,2H),1.74 to 1.56(m,1H),0.74(d, J ═ 6.6, 6H); LC-MS, M/z 482.1[ M + H ] +, tR 2.03min hplc, 95% (214nm), 90% (254nm), tR 8.26min.
EXAMPLE 2 preparation of Compounds 7d and 8d
Compound 7 d: 2- (3-isobutyl-4- (1- (4-fluorobenzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline;
compound 8 d: 2- (3-isobutyl-4- (1- (4-fluorobenzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline.
The structures of compounds 7d and 8d are shown below:
the production of compounds 7d and 8d was carried out using compounds 7c and 8c except that 4-fluorobenzyl bromide was used instead of 3-chlorobenzyl bromide in step (5), to give compounds 7d and 8 d.
2- (3-isobutyl-4- (1- (4-fluorobenzyl) -1H-pyrazol-3-yl) phenoxymethyl) quinoline (7d) with a yield of 25%. NMR (CD3OD,300MHz), δ:9.09(d, J ═ 7.2Hz,1H),8.39(d, J ═ 8.4Hz,1H),8.29(d, J ═ 7.9Hz,1H),8.15 to 8.13(m,2H),7.92(t, J ═ 7.2Hz,1H),7.76(s,1H),7.36 to 7.26(m,3H),7.06 to 7.02(m,4H),6.35(s,1H),5.72(s,2H),5.34(s,2H),2.64(d, J ═ 7.0Hz,2H),1.72 to 1.53(m,1H),0.69(d, J ═ 6.4Hz, 6H); LC-MS, M/z 466.1[ M + H ] +, tR 1.94 min; HPLC, 98% (214nm), 98% (254nm), tR 7.54min.
2- (3-isobutyl-4- (1- (4-fluorobenzyl) -1H-pyrazol-5-yl) phenoxymethyl) quinoline (8d) with a yield of 25%. NMR (CD3OD,300MHz), δ:8.93(d, J ═ 8.4Hz,1H),8.29(d, J ═ 8.6Hz,1H),8.23(d, J ═ 7.9Hz,1H),8.07(t, J ═ 9.1Hz,2H),7.94 to 7.83(M,1H),7.60(d, J ═ 1.8Hz,1H),7.14 to 6.88(M,7H),6.28(d, J ═ 1.8Hz,1H),5.66(s,2H),5.07(s,2H),2.18(d, J ═ 7.1Hz,2H),1.70 to 1.49(M,1H),0.70(d, J ═ 6.5Hz,6H, MS ═ 254 ═ 3.254 nm, (+ 89.89.90 nm), hplc (LC, 89.87 nm).
EXAMPLE 3 preparation of Compounds 7e and 8e
Compound 7 e: 2- (3-isobutyl-4- (1- ((1, 1' -biphenyl) -4-ylmethyl) -1H-pyrazol-3-yl) -phenoxymethyl) quinoline;
compound 8 e: 2- (3-isobutyl-4- (1- ((1, 1' -biphenyl) -4-ylmethyl) -1H-pyrazol-5-yl) -phenoxymethyl) quinoline.
The structures of compounds 7e and 8e are shown below:
the production processes of the compounds 7e and 8e were identical to those of the compounds 7c and 8c except that 4-phenylbenzyl bromide was used instead of 3-chlorobenzyl bromide in the step (5), whereby the compounds 7e and 8e were produced.
2- (3-isobutyl-4- (1- ((1, 1' -biphenyl) -4-ylmethyl) -1H-pyrazol-3-yl) -phenoxymethyl) quinoline (7e), yield 19%. NMR (CD)3OD,300MHz),δ:9.12(d,J＝8.4Hz,1H),8.34(t,J＝7.8Hz,2H),8.17(t,J＝8.4Hz,2H),7.97(t,J＝7.7Hz,1H),7.79(d,J＝2.3Hz,1H),7.64～7.54(m,4H),7.46～7.30(m,6H),7.09～7.01(m,2H),6.39(d,J＝2.3Hz,1H),5.72(s,2H),5.42(s,2H),2.67(d,J＝7.5Hz,2H),1.72～1.58(m,1H),0.70(d,J＝6.6Hz,6H)；LC-MS,m/z:524.3[M+H]+,tR＝2.09min；HPLC,98％(214nm),98％(254nm),tR＝7.07min.
2- (3-isobutyl-4- (1- ((1, 1' -biphenyl) -4-ylmethyl) -1H-pyrazol-5-yl) -phenoxymethyl) quinoline (8e), yield 12%. NMR (CD)3OD,300MHz),δ:8.75(d,J＝8.4Hz,1H),8.20(d,J＝8.4Hz,1H),8.12(d,J＝7.5Hz,1H),8.02～7.91(m,2H),7.78(t,J＝7.2Hz,1H),7.61(d,J＝1.9Hz,1H),7.51～7.47(m,2H),7.44～7.27(m,5H),7.09(d,J＝8.3Hz,1H),7.05～6.97(m,2H),6.94(d,J＝8.2Hz,2H),6.28(d,J＝1.9Hz,1H),5.58(s,2H),5.13(s,2H),2.17(d,J＝7.2Hz,2H),1.63～1.50(m,1H),0.67(d,J＝6.6Hz,6H).LC-MS,m/z:524.3[M+H]+,tR＝2.07min.HPLC,90％(214nm),88％(254nm),tR＝4.70min.
Example 4
The preparation process of the compound described in this example is the same as that of example 1, except that 2-isobutyl-4- (2-quinoline) methoxyacetophenone (compound 3) is prepared in step (2), and the specific process is as follows:
into a reaction flask were successively charged 8.8g (46mmol) of Compound 2, 9.1g (51mmol) of 2-chloromethylquinoline, 3g (9.2mmol) of cesium carbonate and 100ml of DMF. The reaction was stirred at 50 ℃ for 12 h. TLC showed the reaction was complete. The solvent was removed and the crude product was concentrated and separated by column chromatography to give 10.7g of colorless oily liquid compound 3 with a yield of 70%. LC-MS, m/z: 334.2[ M + H ] +.
Example 5
The preparation process of the compound described in this example is the same as that of example 1, except that 2-isobutyl-4- (2-quinoline) methoxyacetophenone (compound 3) is prepared in step (2), and the specific process is as follows:
into a reaction flask were successively charged 8.8g (46mmol) of Compound 2, 9.1g (51mmol) of 2-chloromethylquinoline, 7.5g (23mmol) of cesium carbonate and 100ml of DMF. The reaction was stirred at 60 ℃ for 12 h. TLC showed the reaction was complete. The solvent was removed and the crude product was concentrated and separated by column chromatography to give 9.5g of colorless oily liquid compound 3 with a yield of 62%. LC-MS, m/z: 334.2[ M + H ] +.
Example 6
The preparation process of the compound described in this example is the same as that of example 1, except that 2-isobutyl-4- (2-quinoline) methoxyacetophenone (compound 3) is prepared in step (2), and the specific process is as follows:
into a reaction flask were successively added 8.8g (46mmol) of Compound 2, 9.1g (51mmol) of 2-chloromethylquinoline, 3.2g (23mmol) of potassium carbonate and 100ml of DMF. The reaction was stirred at 50 ℃ for 12 h. TLC showed the reaction was complete. After the solvent was removed, the crude product was concentrated, and 8.1g of colorless oily liquid compound 3 was obtained by column chromatography separation with a yield of 53%. LC-MS, m/z: 334.2[ M + H ] +.
Example 7
The preparation process of the compound described in this example is the same as that of example 1, except that 2-isobutyl-4- (2-quinoline) methoxyacetophenone (compound 3) is prepared in step (2), and the specific process is as follows:
into a reaction flask were successively added 8.8g (46mmol) of Compound 2, 9.1g (51mmol) of 2-chloromethylquinoline, 1.3g (9.2mmol) of potassium carbonate and 100ml of DMF. The reaction was stirred at 50 ℃ for 12 h. TLC showed the reaction was complete. After the solvent was removed, the crude product was concentrated, and then separated by column chromatography to obtain 7.5g of colorless oily liquid compound 3 with a yield of 49%. LC-MS, m/z: 334.2[ M + H ] +.
Example 8
The procedure for the preparation of the compound described in this example was the same as in example 1, except for the preparation of 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline (compound 5) in step (4), which was as follows:
9.5g (24.5mmol) of Compound 4, 12.9g (12.3mmol) of hydrazine hydrochloride, and 120mL of ethanol were sequentially added to the reaction flask, and the reaction was refluxed for 6 hours. TLC showed the reaction was complete. Quenching reaction, removing solvent, concentrating to obtain crude product, and separating by column chromatography to obtain 4.5g white solid compound 5 with yield of 52%. LC-MS, m/z: 358.2[ M + H ] +.
Example 9
The procedure for the preparation of the compound described in this example was the same as in example 1, except for the preparation of 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline (compound 5) in step (4), which was as follows:
9.5g (24.5mmol) of Compound 4, 12.9g (12.3mmol) of hydrazine hydrochloride, and 120mL of ethanol were sequentially added to the reaction flask, and the reaction was refluxed for 10 hours. TLC showed the reaction was complete. Quenching reaction, removing solvent, concentrating to obtain crude product, and separating by column chromatography to obtain 6.6g white solid compound 5 with yield of 76%. LC-MS, m/z: 358.2[ M + H ] +.
Example 10
The procedure for the preparation of the compound described in this example was the same as in example 1, except for the preparation of 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline (compound 5) in step (4), which was as follows:
9.5g (24.5mmol) of Compound 4, 25.8g (24.5mmol) of hydrazine hydrochloride, and 120mL of ethanol were sequentially added to the reaction flask, and the reaction was refluxed for 10 hours. TLC showed the reaction was complete. Quenching reaction, removing solvent, concentrating to obtain crude product, and separating by column chromatography to obtain 6.1g white solid compound 5 with yield of 70%. LC-MS, m/z: 358.2[ M + H ] +.
Example 11
The procedure for the preparation of the compound described in this example was the same as in example 1, except for the preparation of 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline (compound 5) in step (4), which was as follows:
9.5g (24.5mmol) of Compound 4, 25.8g (24.5mmol) of hydrazine hydrochloride, and 120mL of ethanol were sequentially added to the reaction flask, and the reaction was refluxed for 12 hours. TLC showed the reaction was complete. Quenching reaction, removing solvent, concentrating to obtain crude product, and separating by column chromatography to obtain 6.4g white solid compound 5 with yield of 73%. LC-MS, m/z: 358.2[ M + H ] +.
Example 12 biological Activity assay
The synthesized compounds 7c, 8d, 7e and 8e are subjected to bactericidal activity determination by taking botrytis cinerea, fusarium oxysporum f.sp.gossypii, fusarium graminearum and alternaria arachidis as test materials according to a Standard Operation Procedure (SOP) for determination of biological activity of the research center of the international pesticide-creating engineering technology. The mass concentration of the common sieve is 50mg/L, and azoxystrobin (azoxystrobin) is used as a control medicament. The bactericidal activity of the compounds was determined as shown in table 1.
Fungicidal Activity of the Compounds of Table 1 (inhibition/%)
| Compound (I) | Cucumber gray mold | Blight of cotton | Wheat scab germ | Brown spot of peanut |
| 7c | 17.5 | 37.2 | 31.0 | 66.5 |
| 8c | 14.1 | 40.2 | 34.1 | 68.2 |
| 7d | 33.8 | 64.3 | 50.2 | 94.2 |
| 8d | 36.2 | 62.9 | 54.6 | 95.1 |
| 7e | 12.2 | 23.4 | 17.2 | 56.3 |
| 8e | 14.9 | 19.8 | 19.6 | 61.8 |
| Azoxystrobin | 19.4 | 56.3 | 37.6 | 81.2 |
The biological activity test result shows that the 6 synthesized quinoline compounds containing pyrazole rings, namely the compounds 7c, 8d, 7e and 8e have excellent bactericidal activity on cucumber botrytis cinerea, cotton fusarium wilt, wheat fusarium graminearum and peanut brown spot pathogen under the test concentration, and are all obviously superior to the control drug azoxystrobin; among the 4 plant pathogenic bacteria, the compound has the best bactericidal activity on peanut brown spot pathogen, and then cotton fusarium wilt pathogen; among the 6 compounds, the compound 8d has the best sterilization effect on cucumber botrytis cinerea, wheat scab and peanut brown spot, and the inhibition rates of the compound 8d respectively reach 36.2%, 54.6% and 95.1%; the compound 7d has the best bactericidal effect on cotton fusarium wilt, and the inhibition rate reaches 64.3 percent.
In conclusion, the compound has a good inhibition effect on 4 plant pathogenic bacteria, the effect of the compound is obviously superior to that of azoxystrobin serving as a contrast medicament, the compound can be used as a plant bactericide, and the compound has a wide application prospect in the field of prevention and/or treatment of plant diseases.
It should be finally noted that the above examples are only intended to illustrate the technical solutions of the present invention, and not to limit the scope of the present invention, and that other variations and modifications based on the above description and thought may be made by those skilled in the art, and that all embodiments need not be exhaustive. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (10)
1. A quinoline compound is characterized in that the structure of the compound is shown as a formula (I) or a formula (II):
wherein R is1Is one or more of hydroxyl, nitro, amino, halogen, phenyl or halogenated phenyl.
2. The quinolines of claim 1, wherein R is1Is one of bromine, iodine, phenyl or halophenyl.
3. The quinolines of claim 2, wherein R is1Is 3-fluoro, 4-fluoro, 3-chloro, 4-chloro or phenyl.
4. The quinolines of claim 3, wherein R is1Is 3-chloro, 4-fluoro or 4-phenyl.
5. The method for preparing quinoline compounds according to any one of claims 1 to 4, comprising the steps of:
s1, synthesizing 2-isobutyl-4-hydroxyacetophenone by using 2-isobutyl-4-methoxyacetophenone as a raw material; dissolving 2-isobutyl-4-hydroxyacetophenone, 2-halomethylquinoline and carbonate in an organic solvent for reaction to prepare 2-isobutyl-4- (2-quinoline) methoxyacetophenone;
s2, mixing and reacting 2-isobutyl-4- (2-quinoline) methoxyacetophenone, DMF and DMA to obtain (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one; then dissolving the 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline in a polar organic solvent to react with hydrazine to prepare 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline;
s3, finally, 2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline and R1The substituted benzyl bromide compound and carbonate are dissolved in an organic solvent to react to prepare a target product;
the R is1Is one or more of hydroxyl, nitro, amino, halogen, phenyl or halogenated phenyl.
6. The method according to claim 5, wherein the molar ratio of 2-isobutyl-4-hydroxyacetophenone, 2-halomethylquinoline and carbonate in step S1 is 1: 1.1 to 1.5: 0.2 to 0.5; the organic solvent is DMF, and the carbonate is potassium carbonate, sodium carbonate or cesium carbonate; the reaction temperature is 50-60 ℃, and the reaction time is 8-14 h;
in the step S2, the molar ratio of (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one to hydrazine is 1: 0.5-1; the polar organic solvent is ethanol; the reaction conditions are heated and refluxed; the reaction time is 6-12 h;
2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline, R in step S31The molar ratio of the substituted benzyl bromide compound to the carbonate is 1: 1.2-2.0: 1.4-3; the organic solvent is DMF, DMA or DMSO, and the carbonate is potassium carbonate, sodium carbonate or cesium carbonate; the reaction temperature is 40-60 ℃, and the reaction time is 8-14 h.
7. The method according to claim 5, wherein the molar ratio of 2-isobutyl-4-hydroxyacetophenone, 2-chloromethyl quinoline and carbonate in step S1 is 1: 1.1: 0.5; the carbonate is cesium carbonate; the reaction temperature is 60 ℃, and the reaction time is 12 hours;
in step S2, the molar ratio of (E) -3- (N, N-dimethyl) -1- (2-isobutyl-4- (2-methoxyquinoline) phenyl) -2-propen-1-one to hydrazine is 1: 0.5; the reaction time is 12 h;
2- (3-isobutyl-4- (3-pyrazolyl) phenoxymethyl) quinoline, R in step S31The molar ratio of substituted benzyl bromide compound to carbonate salt is 1: 1.67: 2; the organic solvent is DMF, and the carbonate is cesium carbonate; the reaction temperature is 50 ℃, and the reaction time is 12 h.
8. Use of the quinoline compounds according to any one of claims 1 to 4 for the control and/or treatment of plant diseases.
9. Use of the quinoline compounds according to any one of claims 1 to 4 for the preparation of a fungicide.
10. The use according to claim 8, for the control and/or treatment of botrytis cinerea, fusarium oxysporum, fusarium graminearum and alternaria arachidicola.
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| CN106632318A (en) * | 2016-11-04 | 2017-05-10 | 广东环境保护工程职业学院 | Tetrahydropyridopyrimidine compound, preparation method therefor and application of tetrahydropyridopyrimidine compound |
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2018
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101098866A (en) * | 2005-01-07 | 2008-01-02 | 辉瑞产品公司 | Heteroaromatic quinoline compounds and their use as PDE10 inhibitors |
| CN106632318A (en) * | 2016-11-04 | 2017-05-10 | 广东环境保护工程职业学院 | Tetrahydropyridopyrimidine compound, preparation method therefor and application of tetrahydropyridopyrimidine compound |
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| CN109384766A (en) | 2019-02-26 |
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