CN114213311A - Substituted benzaldehyde oxime ester compound and preparation method and application thereof - Google Patents
Substituted benzaldehyde oxime ester compound and preparation method and application thereof Download PDFInfo
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- CN114213311A CN114213311A CN202111616922.1A CN202111616922A CN114213311A CN 114213311 A CN114213311 A CN 114213311A CN 202111616922 A CN202111616922 A CN 202111616922A CN 114213311 A CN114213311 A CN 114213311A
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- -1 benzaldehyde oxime ester compound Chemical class 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 241000221696 Sclerotinia sclerotiorum Species 0.000 claims abstract description 15
- 241000123650 Botrytis cinerea Species 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 241000233616 Phytophthora capsici Species 0.000 claims abstract description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract description 3
- 150000002367 halogens Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 13
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 12
- VTWKXBJHBHYJBI-SOFGYWHQSA-N (ne)-n-benzylidenehydroxylamine Chemical class O\N=C\C1=CC=CC=C1 VTWKXBJHBHYJBI-SOFGYWHQSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims description 5
- 150000003935 benzaldehydes Chemical class 0.000 claims description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 241000233614 Phytophthora Species 0.000 claims description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000417 fungicide Substances 0.000 claims description 4
- 241000223221 Fusarium oxysporum Species 0.000 claims description 3
- 241001330975 Magnaporthe oryzae Species 0.000 claims description 3
- 230000000855 fungicidal effect Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 2
- 241001115351 Physalospora Species 0.000 claims description 2
- 241000813090 Rhizoctonia solani Species 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 229940050176 methyl chloride Drugs 0.000 claims description 2
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims description 2
- 241001290235 Ceratobasidium cereale Species 0.000 claims 1
- 241000082085 Verticillium <Phyllachorales> Species 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 14
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 7
- 240000007594 Oryza sativa Species 0.000 abstract description 5
- 235000007164 Oryza sativa Nutrition 0.000 abstract description 5
- 235000009566 rice Nutrition 0.000 abstract description 5
- 240000008067 Cucumis sativus Species 0.000 abstract description 3
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 abstract description 3
- 230000003385 bacteriostatic effect Effects 0.000 abstract description 2
- 240000002791 Brassica napus Species 0.000 abstract 1
- 235000011293 Brassica napus Nutrition 0.000 abstract 1
- 241001558929 Sclerotium <basidiomycota> Species 0.000 abstract 1
- 244000052616 bacterial pathogen Species 0.000 abstract 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 16
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000003617 indole-3-acetic acid Substances 0.000 description 4
- JTEDVYBZBROSJT-UHFFFAOYSA-N indole-3-butyric acid Chemical compound C1=CC=C2C(CCCC(=O)O)=CNC2=C1 JTEDVYBZBROSJT-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 241000223218 Fusarium Species 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000005648 plant growth regulator Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 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 1
- 241000213004 Alternaria solani Species 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 241000223195 Fusarium graminearum Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000315044 Passalora arachidicola Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VTWKXBJHBHYJBI-UHFFFAOYSA-N n-benzylidenehydroxylamine Chemical class ON=CC1=CC=CC=C1 VTWKXBJHBHYJBI-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
- A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
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)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a substituted benzaldehyde oxime ester compound and a preparation method and application thereof, wherein the structural formula of the substituted benzaldehyde oxime ester compound is shown as the formula (I):
Description
Technical Field
The invention belongs to the field of chemical synthesis and drug application, and particularly relates to a substituted benzaldehyde oxime ester compound and a preparation method and application thereof.
Background
With the progress and development of society, novel heterocyclic compounds have become the key point of pesticide creation and research, and the heterocyclic compounds are favored by people due to the characteristics of greenness, high efficiency, low toxicity, broad spectrum, various structures, easy modification and the like, and particularly, nitrogen-containing heterocyclic compounds with novel structures have become the hot spots of pesticide research and development. The development of compounds with novel structures by taking active natural products as lead compounds has prompted the high-efficiency broad-spectrum biological activity and has become one of the most active fields in recent years.
Because the indole structure has the characteristics of low toxicity to human bodies and good biological activity, the indole structure is widely applied to the fields of pesticides, medicines, foods, dyes and the like, thereby becoming a hot spot of green medicine research. Since Leonian et al first discovered that indole-3-acetic acid has excellent fungicidal activity in 1937, many new varieties of indole heterocycle-containing insecticides, fungicides and plant growth regulators, such as indole esters as fungicides and indole acetic acid (IBA) and indole esters (Figarin) as plant growth regulators, have been developed abroad. The invention designs and synthesizes the novel indole derivative of the substituted benzaldehyde oxime ester compound by taking Serlyticin-A as a lead structure and taking natural products of indoleacetic acid, indole propionic acid or indole butyric acid as raw materials for structural derivation.
Disclosure of Invention
The invention aims to provide a substituted benzaldehyde oxime ester compound and a preparation method and application thereof.
The substituted benzaldehyde oxime ester compound is characterized in that the structural formula is shown as the formula (I):
in the formula (I), n is an integer of 1-3, the number of substituents R on a benzene ring is 1-3, and R is selected from C1-C4 alkyl, halogen, nitro, C1-C4 alkoxy or halogen substituted C1-C4 alkyl.
The substituted benzaldehyde oxime ester compound is characterized in that a substituent R on a benzene ring is 4-methoxy, 2-bromo, 4-methyl, 4-fluoro, 2-nitro, 3-nitro, 2-methoxy, 4-bromo, 3-chloro, 4-trifluoromethyl, 4-chloro, 3,4, 5-trimethoxy, 3, 4-dimethoxy, 2, 4-dichloro or 2,3, 4-trimethoxy.
The preparation method of the substituted benzaldehyde oxime ester compound is characterized by comprising the following steps:
1) adding substituted benzaldehyde shown as a formula (1) into a reactor, adding an alcohol solvent, stirring and dissolving, and then dropwise and slowly adding an aqueous solution of hydroxylamine hydrochloride to react to generate a compound 2 shown as a formula (2);
2) using methyl chloride as a solvent, DMAP as a catalyst and DCC as an activating reagent, and reacting the compound of the formula (2) obtained in the step 1) with a compound raw material of the formula (3) (namely 3-indoleacetic acid, 3-indolepropionic acid or 3-indolebutyric acid) to generate a substituted benzaldehyde oxime ester compound shown as the formula (I); the reaction process is as follows:
the substituent R on the benzene ring in the formula (1) and the formula (2) is the same as that in the formula (I);
in the formula (3), n is an integer of 1-3.
The preparation method of the substituted benzaldehyde oxime ester compound is characterized in that when the compound 2 is synthesized in the step 1), hydroxylamine hydrochloride is dissolved in water and then slowly dripped into a reaction liquid, so that the yield is further improved. Cis-trans isomerism may occur when compound 2 is synthesized, but the oxime has poor stability in the Z configuration and will be converted to the E configuration when encountering acid in an alcohol solution. Therefore, the compound 2 exists in the E configuration.
The preparation method of the substituted benzaldehyde oxime ester compound is characterized in that in the step 1), the feeding molar ratio of substituted benzaldehyde to hydroxylamine hydrochloride to sodium carbonate is 1: 1-1.2: 1.2 to 1.6.
The preparation method of the substituted benzaldehyde oxime ester compound is characterized in that in the step 1), the reaction is carried out for 1-3 hours at room temperature by stirring, and the reaction process is tracked by TLC.
The preparation method of the substituted benzaldehyde oxime ester compound is characterized in that in the step 2), the reaction is carried out for 1-3 hours at room temperature by stirring, and the reaction process is tracked by TLC; the molar ratio of the compound of formula (2) to the compound of formula (3) to DCC to DMAP is 1: 0.8-1.2: 0.8-1.2: 0.4-0.6, preferably 1:1:1: 0.5.
The substituted benzaldehyde oxime ester compound is applied as a bactericide and is characterized in that the substituted benzaldehyde oxime ester compound is used for preparing the bactericide for inhibiting rice blast, phytophthora capsici leonian, cucumber fusarium wilt, apple ring spot, cucumber gray mold, sclerotinia sclerotiorum, rice sheath blight, wheat scab, tomato early blight or peanut brown spot.
The invention provides a preparation method of substituted benzaldehyde oxime ester compounds, which is simple in preparation method and convenient to operate, the structure of the substituted benzaldehyde oxime ester compounds is confirmed by nuclear magnetic hydrogen spectrum, 45 target products are tested for bactericidal activity in the embodiment of the invention, and the result shows that: all the substituted benzaldehyde oxime ester compounds have certain bacteriostatic activity, and the inhibition rate of the D2 compound on sclerotinia sclerotiorum and botrytis cinerea reaches over 75 percent under the concentration of 50 ug/mL; the inhibition rate of the D14 compound on sclerotinia sclerotiorum and botrytis cinerea reaches more than 60% under the concentration of 50 ug/mL; the inhibition rate of the D22 compound on rice blast, phytophthora capsici and sclerotinia sclerotiorum of rape all reaches more than 70 percent under the concentration of 50 ug/mL; the inhibition rate of the D36 compound on sclerotinia sclerotiorum and botrytis cinerea reaches more than 67 percent under the concentration of 50 ug/mL.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
EXAMPLE 1 preparation of Compound 2
A100 mL reaction flask was charged with 1mmol of intermediate 1 (substituted benzaldehyde) and anhydrous ethanol (about 30mL) was used as a solvent, and the mixture was stirred at room temperature to dissolve the intermediate. Dissolving 1.2mmol of hydroxylamine hydrochloride and 1.5mmol of anhydrous sodium carbonate in a small beaker by using a proper amount of water, then slowly dropwise adding the solution into the reaction solution, stirring at room temperature for 1-2h, tracking the reaction progress by TLC (VEA/VPE ═ 1/4, v/v), extracting for 2-3 times by using 10mL of water and 50mL of ethyl acetate after the reaction is finished, collecting an organic phase, finally adding column chromatography silica gel, removing the solvent by rotary evaporation, and finally purifying by column chromatography to obtain an intermediate 2 (the different substituted benzaldehyde oxime). The structure of the intermediate is confirmed by nuclear magnetic resonance hydrogen spectrum, and the intermediate 2 (the differently substituted benzaldoxime) is a known compound.
Example 2 preparation of a compound of formula I (n ═ 3)
See example 1 for the procedure for the preparation of intermediate 2.
Adding dichloromethane (20mL) as a solvent, 4-dimethylaminopyridine (DMAP, 0.5mmol) as a catalyst, N, N' -dicyclohexylcarbodiimide (DCC,1mmol) as an activating reagent, adding an intermediate 2 (substituted benzaldehyde oxime, 1mmol) and a raw material (3-indolebutyric acid, 1mmol), stirring at room temperature for 2 hours, tracking and reacting by TLC (VEA/VPE (1/2, v/v)), cooling and standing after the reaction is finished, performing suction filtration, collecting filtrate, finally adding column chromatography silica gel, removing the solvent by rotary evaporation, and purifying by column chromatography to obtain a pure product of the target compound I.
Example 3 preparation of compound of formula I (n ═ 2)
See example 1 for the procedure for the preparation of intermediate 2.
Adding dichloromethane (20mL) as a solvent, 4-dimethylaminopyridine (DMAP, 0.5mmol) as a catalyst, N, N' -dicyclohexylcarbodiimide (DCC,1mmol) as an activating reagent, adding an intermediate 2 (substituted benzaldehyde oxime, 1mmol) and a raw material (3-indole propionic acid, 1mmol), stirring at room temperature for 2h, tracking and reacting by TLC (VEA/VPE (1/2, v/v)), cooling and standing after the reaction is finished, performing suction filtration, collecting filtrate, finally adding column chromatography silica gel, removing the solvent by rotary evaporation, and purifying by column chromatography to obtain a pure product of the target compound I.
Example 4 preparation of compound of formula I (n ═ 1)
See example 1 for the procedure for the preparation of intermediate 2.
Adding dichloromethane (20mL) as a solvent, 4-dimethylaminopyridine (DMAP, 0.5mmol) as a catalyst, N, N' -dicyclohexylcarbodiimide (DCC,1mmol) as an activating reagent, adding an intermediate 2 (substituted benzaldehyde oxime, 1mmol) and a raw material (3-indoleacetic acid, 1mmol), stirring at room temperature for 2 hours, tracking and reacting by TLC (VEA/VPE (1/2, v/v)), cooling and standing after the reaction is finished, performing suction filtration, collecting filtrate, finally adding column chromatography silica gel, removing the solvent by rotary evaporation, and purifying by column chromatography to obtain a pure product of the target compound I.
The reaction sequence involved in examples 2-4 is as follows:
the substituent R on the benzene ring in the formula (1) and the formula (2) is the same as that in the formula (I); in the formula (3), n is an integer of 1-3. The benzene ring substituent R in the intermediate 1 (substituted benzaldehyde), the intermediate 2 (substituted benzaldehyde oxime) and the target compound I are listed in Table 1, and the appearance and reaction yield of the corresponding target compound are also listed in Table 1. The hydrogen spectra data for each target compound are listed in table 2.
TABLE 1 physicochemical data of substituted benzaldoxime esters
TABLE 2 data of hydrogen spectra of substituted benzaldoxime compounds
Example 5 bactericidal Activity test
Test method
(1) Test subjects: pyricularia oryzae (Pyricularia oryzae), Phytophthora capsici (Phytophthora capsici), Fusarium oxysporum (Fusarium oxysporum), Phytophthora piricola (Physalospora piricola), Botrytis cinerea (Botrytis cinerea), Sclerotinia sclerotiorum (Sclerotinia sclerotiorum), Rhizoctonia solani (Riziotinia solani, Gibberella cerealis (Gibberella zeae), Phytophthora solani (Alternaria solani), and Phytophthora arachidis (Cercospora arachidicola).
(2) And (3) test treatment: the various compounds obtained need to be dissolved in DMSO to obtain EC mother liquor with mass fraction of 1% for standby. Using zone of inhibition method, each compound was evaluated for bactericidal activity in the test target chamber at a concentration of 50ppm, and a control group of clear water (QCK) and a control of indoleacetic acid (FP) with an effective content of 50ppm were additionally provided.
(3) The test method comprises the following steps: firstly, a pipette is used to suck 100 microliter of EC mother liquor, and the EC mother liquor is diluted in Tween water to prepare liquid medicine with the concentration of 500 ppm. Then a liquid transfer gun is used for sucking 1ml of liquid medicine and putting the liquid medicine into a sterilized culture dish, and then 9ml of PDA culture medium is put into the culture dish, and the liquid medicine is shaken up and cooled. And then, beating the round bacterial cake by using a puncher, picking the round bacterial cake to the center of a culture dish by using an inoculating needle, finally placing the culture dish in an incubator at 27 ℃ for culture, and measuring the diameter of a bacterial colony after 48-72 hours. The pure growth amount of the bacterial colony is the difference value of the average diameter of the bacterial colony and the diameter of the bacterial cake, and the calculation method of the inhibition rate (%) refers to the following formula.
The pure growth amount of the control bacterial colony in the bacteriostasis rate calculation formula refers to the result detected under the control of solvent and clear water (QCK).
The results of the activity test are shown in table 3:
TABLE 3 fungicidal activity of substituted benzaldoximes
The bactericidal activity results of the substituted benzaldoxime ester compounds (45) show that (table 3), at the concentration of 50 mu g/mL, 45 samples have certain inhibitory activity to 10 targets, and the inhibition rate of the D2 compound to sclerotinia sclerotiorum and botrytis cinerea reaches over 75% at the concentration of 50 ug/mL; the inhibition rate of the D14 compound on sclerotinia sclerotiorum and botrytis cinerea reaches more than 60% under the concentration of 50 ug/mL; the inhibition rate of the D22 compound on rice blast, phytophthora capsici and sclerotinia sclerotiorum of rape all reaches more than 70 percent under the concentration of 50 ug/mL; the inhibition rate of the D36 compound on sclerotinia sclerotiorum and botrytis cinerea reaches more than 67% under the concentration of 50 ug/mL.
The statements in this specification merely set forth a list of implementations of the inventive concept and the scope of the present invention should not be construed as limited to the particular forms set forth in the examples.
Claims (8)
1. A substituted benzaldehyde oxime ester compound is characterized in that the structural formula is shown as the formula (I):
in the formula (I), n is an integer of 1-3, the number of substituents R on a benzene ring is 1-3, and R is selected from C1-C4 alkyl, halogen, nitro, C1-C4 alkoxy or halogen substituted C1-C4 alkyl.
2. The substituted benzaldoxime compound of claim 1, wherein the substituent R on the benzene ring is 4-methoxy, 2-bromo, 4-methyl, 4-fluoro, 2-nitro, 3-nitro, 2-methoxy, 4-bromo, 3-chloro, 4-trifluoromethyl, 4-chloro, 3,4, 5-trimethoxy, 3, 4-dimethoxy, 2, 4-dichloro or 2,3, 4-trimethoxy.
3. A method for preparing the substituted benzaldoxime compound of claim 1, comprising the steps of:
1) adding substituted benzaldehyde shown in a formula (1) into a reactor, adding an alcohol solvent, stirring and dissolving, and then dropwise and slowly adding an aqueous solution containing sodium carbonate and hydroxylamine hydrochloride to react to generate a compound shown in a formula (2);
2) using methyl chloride as a solvent, DMAP as a catalyst and DCC as an activating reagent, and reacting the compound of the formula (2) obtained in the step 1) with the compound of the formula (3) to generate a substituted benzaldehyde oxime ester compound shown in the formula (I); the reaction process is as follows:
the substituent R on the benzene ring in the formula (1) and the formula (2) is the same as that in the formula (I);
in the formula (3), n is an integer of 1-3.
4. The method for preparing substituted benzaldoxime esters according to claim 3, wherein in step 1), the molar ratio of substituted benzaldoxime to hydroxylamine hydrochloride and sodium carbonate is 1: 1-1.2: 1.2 to 1.6.
5. The method for preparing substituted benzaldoxime esters as claimed in claim 3, wherein the reaction in step 1) is stirred at room temperature for 1-3 h, and TLC tracks the reaction progress.
6. The method for preparing substituted benzaldoxime esters compound as claimed in claim 3, wherein the reaction in step 2) is stirred at room temperature for 1-3 h, TLC tracks the reaction process; the molar ratio of the compound of formula (2) to the compound of formula (3) to DCC to DMAP is 1: 0.8-1.2: 0.8-1.2: 0.4-0.6, preferably 1:1:1: 0.5.
7. The use of the substituted benzaldoxime ester compound of claim 1 as a fungicide.
8. The use as claimed in claim 7, characterized in that the substituted benzaldoxime compounds are used for preparing fungicides for inhibiting Pyricularia oryzae, Phytophthora capsici, Fusarium oxysporum, Verticillium pomonella, Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Rhizoctonia cerealis, Phytophthora solani or Physalospora arachidicola.
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