CN116178263B - Nitro-containing pyrazole carboxamide compound as well as preparation method and application thereof - Google Patents
Nitro-containing pyrazole carboxamide compound as well as preparation method and application thereof Download PDFInfo
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- CN116178263B CN116178263B CN202211669856.9A CN202211669856A CN116178263B CN 116178263 B CN116178263 B CN 116178263B CN 202211669856 A CN202211669856 A CN 202211669856A CN 116178263 B CN116178263 B CN 116178263B
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- -1 pyrazole carboxamide compound Chemical class 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 106
- 125000001424 substituent group Chemical group 0.000 claims abstract description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 241000221662 Sclerotinia Species 0.000 claims abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- 240000007594 Oryza sativa Species 0.000 claims abstract description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims abstract description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 4
- 235000009566 rice Nutrition 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 10
- 239000001632 sodium acetate Substances 0.000 claims description 10
- 235000017281 sodium acetate Nutrition 0.000 claims description 10
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 5
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 claims description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 241000233616 Phytophthora capsici Species 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229940045803 cuprous chloride Drugs 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 4
- 241000123650 Botrytis cinerea Species 0.000 claims description 3
- 241000233614 Phytophthora Species 0.000 claims description 3
- 230000000855 fungicidal effect Effects 0.000 claims description 3
- 241000223218 Fusarium Species 0.000 claims description 2
- 241000223221 Fusarium oxysporum Species 0.000 claims description 2
- 241000209140 Triticum Species 0.000 claims description 2
- 235000021307 Triticum Nutrition 0.000 claims description 2
- 244000052616 bacterial pathogen Species 0.000 claims description 2
- AFLBAXPZSPPPIW-UHFFFAOYSA-N disodium;dioxidoboranylformonitrile Chemical compound [Na+].[Na+].[O-]B([O-])C#N AFLBAXPZSPPPIW-UHFFFAOYSA-N 0.000 claims description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
- 235000010288 sodium nitrite Nutrition 0.000 claims description 2
- 239000000417 fungicide Substances 0.000 claims 2
- 235000017060 Arachis glabrata Nutrition 0.000 claims 1
- 244000105624 Arachis hypogaea Species 0.000 claims 1
- 235000010777 Arachis hypogaea Nutrition 0.000 claims 1
- 235000018262 Arachis monticola Nutrition 0.000 claims 1
- QPJDMGCKMHUXFD-UHFFFAOYSA-N cyanogen chloride Chemical compound ClC#N QPJDMGCKMHUXFD-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 claims 1
- 235000020232 peanut Nutrition 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 13
- 241000894006 Bacteria Species 0.000 abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000001257 hydrogen Substances 0.000 abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 4
- 238000001228 spectrum Methods 0.000 abstract description 4
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 abstract description 3
- 235000007688 Lycopersicon esculentum Nutrition 0.000 abstract description 3
- 240000003768 Solanum lycopersicum Species 0.000 abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- DGOAXBPOVUPPEB-UHFFFAOYSA-N 3-(difluoromethyl)-N-methoxy-1-methyl-N-[1-(2,4,6-trichlorophenyl)propan-2-yl]pyrazole-4-carboxamide Chemical compound C=1N(C)N=C(C(F)F)C=1C(=O)N(OC)C(C)CC1=C(Cl)C=C(Cl)C=C1Cl DGOAXBPOVUPPEB-UHFFFAOYSA-N 0.000 description 2
- 241000213004 Alternaria solani Species 0.000 description 2
- 239000005788 Fluxapyroxad Substances 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 241000813090 Rhizoctonia solani Species 0.000 description 2
- 241000221696 Sclerotinia sclerotiorum Species 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- SXSGXWCSHSVPGB-UHFFFAOYSA-N fluxapyroxad Chemical compound FC(F)C1=NN(C)C=C1C(=O)NC1=CC=CC=C1C1=CC(F)=C(F)C(F)=C1 SXSGXWCSHSVPGB-UHFFFAOYSA-N 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- 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
- 241000223600 Alternaria Species 0.000 description 1
- 241000555706 Botryosphaeria dothidea Species 0.000 description 1
- 241001465180 Botrytis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000609458 Corynespora Species 0.000 description 1
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241001344131 Magnaporthe grisea Species 0.000 description 1
- 241001330975 Magnaporthe oryzae Species 0.000 description 1
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
- 241000315044 Passalora arachidicola Species 0.000 description 1
- 241001361634 Rhizoctonia Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
-
- 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
- A01P3/00—Fungicides
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)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a nitro-containing pyrazole carboxamide compound, a preparation method and application thereof, wherein the structural formula of the compound is shown as formula (I): In the formula (I), the substituent R 1 is methyl or chlorine; the substituent R 2 is methyl or substituted phenyl, the number of the substituent groups of the substituted phenyl is 1-2, and each substituent group is independently selected from methyl, cyano or chlorine; the substituent R 3 is methyl, difluoromethyl or trifluoromethyl. The structure of the product obtained by the invention is confirmed by nuclear magnetic hydrogen spectrum, and the obtained 14 target products are subjected to bactericidal activity test, and the result shows that: at the concentration of 50ppm, all the compounds have certain antibacterial activity, wherein the inhibition rate of the compound I-3 on tomato early blight bacteria, rice blast bacteria and sclerotinia rot bacteria reaches more than 60 percent.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis and pharmaceutical application, and particularly relates to a nitro-containing pyrazole formylhydroxylamine compound, and a preparation method and application thereof.
Background
The succinate dehydrogenase inhibitor bactericide has the advantages of specific action, strong efficacy, lasting action and remarkable yield increasing effect, and is always researched and developed by a plurality of pesticide companies at home and abroad. In 2016, the n-da company introduces active methoxy group at the nitrogen atom of the traditional amide bond, and successfully develops the novel pyrazole amide SDHIs bactericide, namely fluxapyroxad hydroxylamine (Pydiflumetofen) by extending the carbon chain of the amine part. It has excellent activity to powdery mildew and leaf spot, broad bactericidal spectrum, wide acting crop, and excellent preventing and controlling effect to grains, corn, soybean, rape, vegetable, special crop, etc. And is effective against diseases which are difficult to control, such as diseases caused by pathogenic bacteria, such as botrytis, sclerotinia, and corynespora. And also can prevent and treat diseases caused by fusarium, such as scab, etc.
Disclosure of Invention
The invention aims to provide a nitro-containing pyrazole carboxamide compound as well as a preparation method and application thereof. In order to research a greener and lower-toxicity safe pesticide, pydiflumetofen is used as a lead compound, active group methoxyamine in fluxapyroxad hydroxylamine is modified into aromatic benzyloxy amine, difluoromethyl at the 3 rd position on a pyrazole ring is replaced, and different electron-withdrawing substituents and electron-donating substituents are connected to groups on benzene rings of an amine part. Through the structure derivative, new nitro-containing pyrazole carboxamide compounds are designed and synthesized.
The structural formula of the nitro-containing pyrazole carboxamide compound is shown as the formula (I):
In the formula (I), the substituent R 1 is methyl or chlorine; the substituent R 2 is methyl or substituted phenyl, the number of the substituent groups of the substituted phenyl is 1-2, and each substituent group is independently selected from methyl, cyano or chlorine; the substituent R 3 is methyl, difluoromethyl or trifluoromethyl.
Preferably, in the substituent R 2, the substituent of the substituted phenyl group is 3, 4-dichloro, 4-cyano, 2-chloro-thiazol-5-yl, 2-methyl or 2-chloro.
The preparation method of the nitro-containing pyrazole carboxamide compound comprises the following steps of;
1) Taking water as a solvent, taking a compound shown as a formula (II) as a raw material, and reacting with HBF 4 in the presence of sodium nitrite to generate a compound shown as a formula (III);
2) Using acetone as a solvent, and reacting a compound shown in a formula (III) with isopropenyl acetate in the presence of cuprous chloride and sodium acetate to generate a compound shown in a formula (IV);
3) Using a compound shown in a formula (V) as a raw material, and reacting the compound shown in a formula (VI) with the compound shown in a formula (VI) in DMF in the presence of sodium hydroxide to generate a compound shown in a formula (VII);
4) Reacting a compound shown in a formula (VII) with hydrazine hydrate to generate a compound shown in a formula (VIII);
5) Reacting the compound shown in the formula (IV) obtained in the step 2) with the compound shown in the formula (VIII) obtained in the step 4) in THF in the presence of sodium acetate to generate a compound shown in the formula (IX);
6) Reacting a compound represented by formula (IX) with sodium cyanoboroate in acetic acid to produce a compound represented by formula (X);
7) Reacting a compound shown in a formula (X) with a compound shown in a formula (XI) in the presence of triethylamine by using dichloromethane as a solvent to obtain a nitro-containing pyrazole formyloxy amine compound shown in a formula (I);
The substituents R 1、R2 and R 3 in the formulae (II) to (XI) are the same as the substituents at the corresponding positions in the formula (I). The reaction process is as follows:
Further, in the step 1), when the compound shown as the formula (III) is synthesized, the mass ratio of the compound shown as the formula (II) to the NaNO 2 is 1:1-1:1.5.
Further, in the step 2), when the compound shown in the formula (IV) is synthesized, the mass ratio of the compound shown in the formula (III), the isopropenyl acetate, the cuprous chloride and the sodium acetate is 1:4-6:0.1-0.2:2-3.
Further, in the step 3), when the compound shown as the formula (VII) is synthesized, the mass ratio of the compound shown as the formula (V), sodium hydroxide and the compound shown as the formula (VI) is 1-1.1:1-1.1:1, a step of; the molar concentration of the compound of formula (V) in DMF is 0.4 to 0.8mol/L.
Further, in the synthesis of the compound represented by the formula (VIII) in the step 4), the mass ratio of the compound represented by the formula (VII) to the hydrazine hydrate is 1:1.3-1.7.
Further, in the synthesis of the compound represented by the formula (IX) in the step 5), the mass ratio of the compound represented by the formula (IV) to the compound represented by the formula (VIII) to sodium acetate is 1:1-1.1:1.5-2.5; the molar concentration of the compound of formula (IV) in THF is 0.4-0.8 mol/L.
Further, in the synthesis of the compound represented by the formula (X) in the step 6), the mass ratio of the compound represented by the formula (IX) to the sodium cyanoborohydride is 1:2-2.5.
Further, in the synthesis of the nitro group-containing pyrazole carboxamide compound in step 7), the mass ratio of the compound represented by the formula (x), the compound represented by the formula (xi) to the triethylamine is 1:1:3.
The application of the nitro-containing pyrazole carboxamide compounds in preparing bactericides.
The invention has the beneficial effects that:
The structure of the product obtained by the invention is confirmed by nuclear magnetic hydrogen spectrum, and the obtained 14 target products are subjected to bactericidal activity test, and the result shows that: all the compounds have certain antibacterial activity, wherein the inhibition rate of the compound I-3 on tomato early blight bacteria, rice blast bacteria and sclerotinia rot bacteria (79.4%) is up to more than 60%. Secondly, the inhibition effect of the compound I-10 on the apple ring rot is 69.2 percent. In addition, the inhibition rate of the compound I-12 to phytophthora capsici is 42.4%.
Detailed Description
The invention will be further illustrated with reference to specific examples, but the scope of the invention is not limited thereto.
Example 1
The preparation method of the nitro-containing pyrazole carboxamide compound comprises the following steps:
1) Preparation of Compounds of formula (III)
A250 mL three-neck flask is sequentially added with substituted-2-nitroaniline (80.0 mmol), 28mL HBF 4 aqueous solution with the mass fraction of 50% and 30mL water, dissolved and stirred at normal temperature for 10min, cooled to about 0 ℃, and then NaNO 2 (80.0 mmol) saturated aqueous solution is added dropwise, a large amount of light yellow solid is generated, the temperature is controlled below 5 ℃, and when the solid is not obviously increased, the reaction is continued for 1h, and then the reaction is stopped. Filtering, washing the solid with water and diethyl ether (20 mL×3), dissolving the solid with acetone, and crystallizing with diethyl ether to obtain a compound shown in formula (III) as pale yellow solid.
2) Preparation of Compounds of formula (IV)
To a 100mL round bottom flask, isopropenyl acetate (190.0 mmol), cuCl (6.0 mmol) and sodium acetate (79.0 mmol) were sequentially added and dissolved with 20mL of acetone, after stirring for 5min, intermediate compound (III) (39.0 mmol) was slowly added in portions, stirred at room temperature, TLC (V EA/VPE =1:5) followed by reaction progress, 6h reaction was completed, solvent was dried by spin-drying, and the compound represented by formula (IV) was purified by column chromatography (eluent V EA/VPE =1:5) to give a yield of 55%.
3) Preparation of Compounds of formula (VII)
N-hydroxyphthalimide (20.0 mmol) and NaOH (20.0 mmol) were sequentially added to a 50mL round bottom flask in 30mL DMF, and after stirring at room temperature for 15 minutes, compound (VI) (19.0 mmol) was added, stirring at room temperature was performed, TLC (V EA/VPE =1:2) followed by the reaction progress, and after completion of 10 hours, the reaction was introduced into ice water to precipitate a large amount of pale yellow solid, to obtain compound (VII).
4) Preparation of Compounds of formula (VIII)
Intermediate compound (vii) (16.8 mmol), 80% by mass aqueous hydrazine hydrate (15.75 g,25.0 mmol) was dissolved in 20mL methanol solution in a 50mL round bottom flask, heated to reflux, after 3h, a large amount of white solid was produced, TLC (V EA/VPE =1:1) monitored for reaction completion, suction filtration, spin-drying of the solvent, ether washing, spin-drying of the solvent to give compound (viii) as a yellow liquid.
5) Preparation of Compounds of formula (IX)
To a 100mL round bottom flask, the intermediate compound (IV) (20.0 mmol), the intermediate compound (VIII) (21.0 mmol) and sodium acetate (3.28 g,40.0 mmol) were sequentially added in 30mL THF solution, stirred at 50℃and TLC (V EA/VPE =1:5) followed by reaction progress, and after 3 hours of reaction, the solvent was dried by spinning to obtain a crude intermediate compound (IX), and the crude intermediate compound was directly fed into the next reaction without purification.
6) Preparation of Compounds of formula (X)
To a 100mL round-bottom flask was added the intermediate compound (IX) (20.0 mmol) and dissolved with 20mL acetic acid, naBH 3 CN (40.0 mmol) was added slowly in portions at room temperature, stirred at room temperature, TLC (V EA/VPE =1:4) followed by reaction progress, 3h reaction was completed, the solvent was spun-dried, pH was adjusted to around 9-10 with aqueous NaOH solution, the aqueous EA extract (10 mL. Times.3) was spun-dried, and the solvent was purified by column chromatography (eluent V EA/VPE =1:4) to give the intermediate compound (X).
7) Preparation of Compounds of formula (I)
In a 50mL round bottom flask, the intermediate compound (X) (1.0 mmol) and Et 3 N (3.0 mmol) were dissolved in 5mL of dichloromethane, and compound (XI) (1.0 mmol) dissolved in 2mL of dichloromethane was slowly added dropwise, and after the addition, stirring was performed at room temperature, TLC (V EA/VPE =1:2) followed by reaction progress, the reaction was completed for 4 hours, the solvent was dried by spin-drying, and purification by column chromatography (eluent V EA/VPE =1:2) was performed to obtain the objective compound. Wherein the structural formula of the related compound is as follows:
Examples I-1 to I-14 preparation method the above procedure was repeated, the substituents R 1、R2 and R 3 in the formulae (II) to (XI) were the same as the substituents at the corresponding positions in the formula (I), and see Table 1, and the yields and physicochemical data of the final target products obtained are summarized in Table 1. The data on the hydrogen spectrum of the target products obtained in examples I-1 to I-14 are summarized in Table 2.
TABLE 1 physical data of nitro group-containing pyrazole carboxamides
TABLE 2 Hydrogen profile data for nitro-containing pyrazole carboxamides
Example 2 bactericidal activity test
Test method
(1) Test object: the plant species include, but are not limited to, alternaria solani (Alternariasolani), alternaria wheat (FusaHum graminearum Sehw), pyricularia oryzae (Pyricularia Grisea), phytophthora capsici (Phytophthora capsiciLeonian), sclerotinia sclerotiorum (Sclerotinia sclerotiorum (Lib.) de Bary), botrytis cinerea (Botrytis cinerea), rhizoctonia solani (Thanatephoruscucumeris), fusarium oxysporum (sp. Cucumebium Owen), phytophthora arachnoidis (Cercospora arachidicola Hori), and Rhizoctonia mali (Botryosphaeria dothidea).
(2) Test treatment: each test compound was dissolved in DMSO to 1% ec stock solution for use. And evaluating the indoor bactericidal activity of the compound to be tested on the test target at a dose of 50ppm by adopting a bacteriostasis circle method, and additionally setting a clear water contrast (QCK).
(3) The test method comprises the following steps: 150 microliters of the EC mother liquor prepared above was sucked by a pipette and dissolved in Tween water to prepare a drug solution with an effective concentration of 500ppm of the compound to be tested. 1ml of the liquid medicine is sucked by a pipette, placed in a sterilized culture dish, placed in 9ml of PDA culture medium, shaken uniformly and cooled. After taking out the circular bacterial cake by a puncher, picking up the circular bacterial cake to the center of a culture dish by an inoculating needle, then placing the culture dish in an incubator at 27 ℃ for culturing, and measuring the colony diameter after 48 hours. The pure growth of the bacterial colony is the difference value between the average diameter of the bacterial colony and the diameter of a bacterial cake, and the calculation method of the bacteriostasis rate (%) refers to the following formula.
The activity test results are shown in table 3:
TABLE 3 fungicidal activity (i.e., inhibition, unit%) of nitro-containing pyrazole carboxamides
The bactericidal activity results of the nitro-containing pyrazole carboxamide compounds (14) show that (Table 3), the inhibition rate of the compound I-3 on tomato early blight bacteria, rice blast bacteria and sclerotinia rot bacteria (79.4%) is more than 60%. Secondly, the inhibition effect of the compound I-10 on the apple ring rot is 69.2 percent. In addition, the inhibition rate of the compound I-12 to phytophthora capsici is 42.4%. Comparison was made by the bactericidal activity of the above compounds: when R 1 is an electron-withdrawing atom Cl, R 2 is a polysubstituted electron-withdrawing atom, and R 3 is-CHF 2, the compound has optimal bactericidal activity.
What has been described in this specification is merely an enumeration of possible forms of implementation for the inventive concept, and the scope of protection of the present invention should not be construed as limited to the specific forms set forth in the examples, nor is it intended that the scope of protection of the present invention be limited to only equivalent technical means as would occur to those skilled in the art based on the inventive concept.
Claims (10)
1. The nitryl-containing pyrazole carboxamide compound is characterized in that the structural formula is shown as the formula (I):
In the formula (I), the substituent R 1 is methyl or chlorine; the substituent R 2 is methyl or substituted phenyl, the number of the substituent groups of the substituted phenyl is 1-2, and each substituent group is independently selected from methyl, cyano, chlorine or 2-chloro-thiazole-5-yl; the substituent R 3 is methyl, difluoromethyl or trifluoromethyl.
2. The nitro-containing pyrazole carboxamides according to claim 1, wherein in the substituents R 2, the substituents of the substituted phenyl groups are 3, 4-dichloro, 4-cyano, 2-methyl, 2-chloro or 2-chloro-thiazol-5-yl.
3. A process for the preparation of a nitro-group-containing pyrazole carboxamide compound according to claim 1, characterised in that it comprises the following steps;
1) Taking water as a solvent, taking a compound shown as a formula (II) as a raw material, and reacting with HBF 4 in the presence of sodium nitrite to generate a compound shown as a formula (III);
2) Using acetone as a solvent, and reacting a compound shown in a formula (III) with isopropenyl acetate in the presence of cuprous chloride and sodium acetate to generate a compound shown in a formula (IV);
3) Using a compound shown in a formula (V) as a raw material, and reacting the compound shown in a formula (VI) with the compound shown in a formula (VI) in DMF in the presence of sodium hydroxide to generate a compound shown in a formula (VII);
4) Reacting a compound shown in a formula (VII) with hydrazine hydrate to generate a compound shown in a formula (VIII);
5) Reacting the compound shown in the formula (IV) obtained in the step 2) with the compound shown in the formula (VIII) obtained in the step 4) in THF in the presence of sodium acetate to generate a compound shown in the formula (IX);
6) Reacting a compound represented by formula (IX) with sodium cyanoboroate in acetic acid to produce a compound represented by formula (X);
7) Reacting a compound shown in a formula (X) with a compound shown in a formula (XI) in the presence of triethylamine by using dichloromethane as a solvent to obtain a nitro-containing pyrazole formyloxy amine compound shown in a formula (I);
Substituents R 1、R2 and R 3 in the formulae (II) to (XI) are the same as the substituents at the corresponding positions in the formula (I).
4. The process for producing a nitro-group-containing pyrazole carboxamide compound according to claim 3, characterized in that, when the compound of formula (III) is synthesized in step 1), the mass ratio of the compound of formula (II) to NaNO 2 is 1:1 to 1:1.5.
5. The method for producing a nitro-group-containing pyrazole carboxamide compound according to claim 3, wherein when the compound represented by the formula (iv) is synthesized in step 2), the mass ratio of the compound represented by the formula (iii), isopropenyl acetate, cuprous chloride, sodium acetate is 1:4-6:0.1-0.2:2-3.
6. The process for producing a nitro-group-containing pyrazole carboxamide compound according to claim 3, wherein in the synthesis of the compound represented by the formula (VII) in step 3), the mass ratio of the compound represented by the formula (V), sodium hydroxide, and the compound represented by the formula (VI) is 1 to 1.1:1-1.1:1, a step of; the molar concentration of the compound shown in the formula (V) in DMF is 0.4-0.8 mol/L.
7. The process for producing a nitro-group-containing pyrazole carboxamide compound according to claim 3, characterized in that, in the synthesis of the compound represented by the formula (viii) in step 4), the mass ratio of the compound represented by the formula (vii) to the hydrazine hydrate is 1:1.3-1.7.
8. The process for producing a nitro-group-containing pyrazole carboxamides according to claim 3, wherein in the synthesis of the compound of formula (ix) in step 5), the mass ratio of the compound of formula (iv) to the compound of formula (viii) to sodium acetate is 1:1-1.1:1.5-2.5; the molar concentration of the compound shown in the formula (IV) in THF is 0.4-0.8 mol/L.
9. The process for producing a nitro-group-containing pyrazole carboxamide compound according to claim 3, characterized in that, in the synthesis of the compound represented by the formula (x) in step 6), the mass ratio of the compound represented by the formula (ix) to sodium cyanoborohydride is 1:2-2.5; in the step 7), the mass ratio of the compound represented by the formula (X), the compound represented by the formula (XI) to the triethylamine is 1:1:3.
10. Use of a nitro-group-containing pyrazole carboxamide compound according to claim 1 or 2 for the preparation of a fungicide, characterized in that the fungicide is for the inhibition of pathogenic bacteria selected from the group consisting of phytophthora solani, gibberella wheat, rice blast, phytophthora capsici, sclerotinia rot, botrytis cinerea, sheath blight, fusarium oxysporum, peanut brown spot and apple ring rot.
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