CN110330455B - Amide derivative, preparation method and application thereof - Google Patents
Amide derivative, preparation method and application thereof Download PDFInfo
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- CN110330455B CN110330455B CN201910472351.5A CN201910472351A CN110330455B CN 110330455 B CN110330455 B CN 110330455B CN 201910472351 A CN201910472351 A CN 201910472351A CN 110330455 B CN110330455 B CN 110330455B
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- 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
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- 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
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to an amide derivative, a preparation method and application thereof, wherein the compound is an amide derivative containing a 3-bromo-5-chloro (fluoro) phenyl unit, has obvious insecticidal activity and can be used for killing various biological insect pests. The preparation method based on the amide derivative is simple and feasible, and the raw materials are easy to obtain; the pesticide based on the amide derivative has good efficacy of killing biological pests.
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to an amide derivative, a preparation method and application thereof.
Background
The direction of modern agricultural development in China has clearly required the development of comprehensive technology for implementing reduction and synergy on chemical fertilizers and pesticides, excessive frequent use of chemical pesticides at present has led to a plurality of agriculture and forestry pests to generate obvious drug resistance on the existing agrochemicals, and the novel high-efficiency low-toxicity compound with a continuous development structure is one of the important means for solving the existing chemical pesticide resistance at present and is also a key technical problem to be solved urgently by the current comprehensive technology for pesticide reduction and synergy.
Functional molecules containing amide building blocks, which are also the main functional groups constituting the primary structure of proteins and polypeptides, are well known in nature. The amide compounds have very important application in the aspects of medicinal chemistry, biochemistry, high polymer materials and the like. Various enzymes in the field of life science and polymer materials widely used in daily life and the like all contain a large number of amide bonds; the amide structure is also an important functional group of a plurality of small molecule drugs, and about 25% of the small molecule drugs sold at present are counted to contain at least one amide bond in the molecular structure of the drug; meanwhile, the amide compounds are also functional molecules which occupy larger proportion in the current agricultural medicine field, and have broad-spectrum biological activity, such as disinsection, sterilization, weeding and the like. However, the existing amide structure pesticides still cannot meet the increasing demands of comprehensive prevention and control of agriculture and forestry.
Disclosure of Invention
In order to solve the problems existing in the prior art, the first aspect of the invention provides an amide derivative containing a 3-bromo-5-chloro (fluoro) phenyl unit, which has obvious insecticidal activity and can be used for killing various biological insect pests.
In order to achieve the above object, the amide derivative of the present invention is a compound represented by the formula (I),
wherein:
R 1 one selected from the following groups:
R 2 and R is 3 Each independently is-H, -CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 ) 2 、 n-Bu、t-Bu、-CH 2 CH 2 OH、-CH 2 CH 2 OCH 2 CH 2 OH、-CH 2 CH 2 OCH 2 CH 2 OCH 3 、 -CH 2 CH 2 NHCH 2 CH 2 OCH 3 、-CH 2 CH 2 OCH 3 、-CH 2 CH(OH)CH 3 、-CH 2 COCH 3 、 -NH 2 、
Or R is 2 And R is 3 Together with the nitrogen atom to which they are attached form
X is chlorine or fluorine.
The amide derivatives of the invention also comprise stereoisomers, tautomers, solvates or pharmaceutically acceptable salts of the compounds shown in the formula (I).
Preferably, the amide derivative of the present invention has one of the following structures:
the second aspect of the invention provides a preparation method of the amide derivative, which is simple and easy to implement, has easily available raw materials and can be used for rapidly preparing the amide derivative.
The preparation method of the invention comprises the following steps: (i) The substituted anthranilic acid compound (1) is taken as a raw material, and an intermediate bromo-anthranilic acid compound (2) is prepared through bromination reaction; (ii) The bromo-anthranilic acid compound (2) and the substituted carboxylic acid (3) undergo a heterocyclic reaction under the action of methanesulfonyl chloride and an alkaline catalyst to obtain a heterocyclic intermediate substituted benzoxazinone (4); (iii) The substituted benzoxazinone (4) is subjected to ring opening under the action of substituted amine (5) to obtain an amide derivative (I);
wherein the substituted anthranilic acid compound (1), the bromo-anthranilic acid compound (2), the substituted carboxylic acid (3), the substituted benzoxazinone (4) and the substituted amine (5) have the following reaction formulas in the preparation process:
preferably, in the step (1), the reaction temperature is 0-45 ℃, and the reaction solvent is 1, 2-dichloroethane, dichloromethane, acetonitrile, tetrahydrofuran, ethyl acetate, acetone, N-dimethylacetamide, N-dimethylformamide or acetic acid, and the brominating reagent is bromine, dibromohydantoin or N-bromosuccinimide.
Preferably, in the step (2), the reaction temperature is 20-50 ℃, the reaction solvent is 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, dichloromethane, acetone or ethyl acetate, and the base is triethylamine, pyridine or potassium carbonate.
Preferably, in the step (3), the reaction temperature is 10-60 ℃, and the reaction solvent is diethyl ether, acetonitrile, tetrahydrofuran, dichloromethane, chloroform, dioxane, acetone or ethyl acetate.
In a third aspect the present invention provides an insecticide comprising the amide derivative as described above and a diluent;
wherein the weight percentage of the amide derivative is 0.001-99.99%;
the diluent is one or more of dimethylbenzene, chlorobenzene, toluene, 1, 2-dichloroethane, 1, 2-dibromoethane, methanol, ethanol, propanol, isopropanol, glycerol, N-dimethylformamide, ethyl acetate, acetone, butanone, cyclohexanone, dimethyl sulfoxide and paraffin; or one or more of kaolin, bentonite, clay, diatomite, montmorillonite, activated clay, dolomite, quartz, calcium carbonate, oxide film, talcum and attapulgite; or one or more of alkyl sulfonate, alkylaryl sulfonate, sorbitol polyoxyethylene ester, polyoxyethylene-fatty alcohol ether, polyoxyethylene-fatty acid ester, aralkyl polyethylene glycol ether, fluoroalkyl sulfonate, alkyl sulfate, lignin sulfonate, polyethylene glycol and rhamnolipid; or one or more of polyvinyl alcohol, carboxymethyl cellulose and acacia; or one or more of inorganic dye, organic dye and trace nutrient.
Preferably, the amide derivative accounts for 5-25% by weight.
Preferably, the insecticide may be an aqueous emulsion, a suspension, a wettable powder or a water dispersible granule.
The fourth aspect of the invention provides an application of the amide derivative or the pesticide in killing biological insect pests, wherein the biological insect pests are cotton bollworms, plutella xylostella, tea geometrid, ash geometrid, tea caterpillar, leaf roller moths, tea leaf hoppers, tea headworms, tea thrips, tea lissajo, tea horn thorn, lygus lucorum, rice leaf rollers, aphids, plant hoppers, whiteflies, prodenia litura, tobacco noctuid, tobacco aphid, armyworms, striped rice borers, yellow rice borers, bean pod borers, root knot nematodes, asian corn borers, soybean borers, peach borers, cinnabarines, citrus red spiders, leaf mites and culex.
The beneficial effects are that:
the amide derivative has obvious insecticidal activity, has a killing rate of more than 70% on at least one of cotton bollworms, aphids, tea geometrid and other pests, and can be widely applied to the comprehensive prevention and control process of agricultural and forestry pests.
Detailed Description
The present invention is described in further detail below by way of specific examples, which are not to be construed as limiting the invention, but are merely illustrative.
Example 1
The amide derivative of the present invention having a 3-bromo-5-chloro (fluoro) phenyl unit in part has a structural formula as one of the specific compounds listed in table 1:
table 1: representative Structure of Compounds of formula (I)
Example 2
The preparation of an intermediate 3-bromo-5-chloro-anthranilic acid 2a has the following reaction formula:
the preparation method comprises the following steps: 5-chloro-o-aminobenzoic acid (compound 1 a) is used as a starting material, an intermediate 3-bromo-5-chloro-o-aminobenzoic acid 2a is prepared under the action of bromine, the reaction temperature is 0-15 ℃, and the reaction solvent is AcOH; spectral data for compound 2 a: MS (ESI) M/z 250.2 (M+H) + ,calcd.for C 7 H 5 BrClNO 2 m/z＝248.9。
Example 3
The preparation of an intermediate 3-bromo-5-chloro-anthranilic acid 2a has the following reaction formula:
the preparation method comprises the following steps: 5-chloro-anthranilic acid (compound 1 a) is used as a starting material, an intermediate 3-bromo-5-chloro-anthranilic acid 2a is prepared under the action of N-bromosuccinimide (NBS), the reaction temperature is 20-25 ℃, and the reaction solvent is DMF; spectroscopic data for compound 2a are as for example 2.
Example 4
The preparation of an intermediate 3-bromo-5-fluoroanthranilic acid 2b has the following reaction formula:
the preparation method comprises the following steps: 5-fluoro-anthranilic acid (compound 1 b) is used as a starting material, an intermediate 3-bromo-5-fluoro-anthranilic acid 2b is prepared under the action of N-bromosuccinimide (NBS), the reaction temperature is 20-25 ℃, and the reaction solvent is DMF; spectral data for compound 2 b: MS (ESI) M/z 234.2 (M+H) + , calcd.for C 7 H 5 BrFNO 2 m/z＝232.9。
Example 5
The preparation of an intermediate 3-bromo-5-fluoroanthranilic acid 2b has the following reaction formula:
the preparation method comprises the following steps: 5-fluoroanthranilic acid (compound 1 b) is used as a starting material, an intermediate 3-bromo-5-fluoroanthranilic acid 2b is prepared under the action of dimethylhydantoin, the reaction temperature is 20-25 ℃, and the reaction solvent is DMF; spectroscopic data for compound 2b are as for example 4.
Example 6
The preparation of intermediate substituted benzoxazinone 4aa has the following reaction formula:
the preparation method comprises the following steps: 3-bromo-5-chloro-anthranilic acid 2a and 2-methyl-3- (4-trifluoromethoxyphenyl) benzoic acid 3a are used as starting materials to prepare an intermediate 6-chloro-2- [ 2-methyl-3- (4-trifluoromethoxyphenyl) phenyl under the action of methanesulfonyl chloride and triethylamine]-8-bromo-4H-benzoxazin-4-one 4aa at 25 ℃ with acetonitrile as the reaction solvent; spectroscopic data for compound 4 aa: MS (ESI) M/z 510.2 (M+H) + ,calcd.for C 22 H 12 BrClF 3 NO 3 m/z＝509.0。
Example 7
The preparation of intermediate substituted benzoxazinone 4ab has the following reaction formula:
the preparation method comprises the following steps: 3-bromo-5-fluoro-anthranilic acid 2b and 2-methyl-3- (4-trifluoromethoxyphenyl) benzoic acid 3a are used as starting materials to prepare an intermediate 6-chloro-2- [ 2-methyl-3- (4-trifluoromethoxyphenyl) phenyl under the action of methanesulfonyl chloride and pyridine]-8-bromo-4H-benzoxazin-4-one 4ab at 25 ℃ with tetrahydrofuran as the reaction solvent; spectral data for compound 4 ab: MS (ESI) M/z 494.2 (M+H) + ,calcd.for C 22 H 12 BrF 4 NO 3 m/z＝493.0。
Example 8
A process for the preparation of an intermediate substituted benzoxazinone 4ba, which has the following formula:
the preparation method comprises the following steps: 3-bromo-5-chloro-anthranilic acid 2a and polysubstituted picolinic acid 3b are used as starting materials, intermediate polysubstituted benzoxazine-4-one 4ba is prepared under the action of methanesulfonyl chloride and triethylamine, the reaction temperature is 25 ℃, and the reaction solvent is tetrahydrofuran; spectroscopic data for compound 4 ba: MS (ESI) M/z 600.2 (M+H) + , calcd.for C 20 H 6 BrCl 2 F 6 N 3 O 3 m/z＝598.9。
Example 9
The preparation of intermediate substituted benzoxazinone 4fa has the following reaction formula:
the preparation method comprises the following steps: 3-bromo-5-chloro-anthranilic acid 2a and substituted pyridylpyrazole formic acid 3f are used as starting materials, an intermediate polysubstituted benzoxazine-4-one 4fa is prepared under the action of methanesulfonyl chloride and pyridine, the reaction temperature is 25 ℃, and the reaction solvent is tetrahydrofuran; spectral data for compound 4 fa: MS (ESI) M/z 514.9 (M+Na) + , calcd.for C 16 H 6 Br 2 Cl 2 N 4 O 2 m/z＝513.8。
Example 10
The preparation of intermediate substituted benzoxazinone 4fb has the following reaction formula:
the preparation method comprises the following steps: taking 3-bromo-5-fluoroanthranilic acid 2b and substituted pyridylpyrazole formic acid 3f as starting materials, preparing an intermediate polysubstituted benzoxazine-4-one 4fb under the action of methanesulfonyl chloride and triethylamine, wherein the reaction temperature is 25 ℃, and the reaction solvent is tetrahydrofuran; spectral data for compound 4 fb: MS (ESI) M/z 499.1 (M+H) + ,calcd.for C 16 H 6 Br 2 ClFN 4 O 2 m/z＝497.9。
Example 11
A compound of example 1, numbered I1, prepared according to the formula:
the preparation method comprises the following steps: the obtained heterocyclic intermediate 4aa is dissolved in proper amount of acetone, and ring opening reaction is carried out under the action of ammonia water to obtain the target compound I1, wherein the reaction temperature is 25-30 ℃, and the reaction solvent is acetone. Spectroscopic data for the target compound I1: MS (ESI) M/z 551.1 (M+Na) + ,calcd.for C 22 H 15 BrClF 3 N 2 O 3 m/z ＝527.7.
Example 12
A process for the preparation of the compound numbered I32 in example 1, which has the formula:
the preparation method comprises the following steps: the obtained heterocyclic intermediate 4fa is dissolved in a proper amount of 1, 2-dichloroethane, and ring-opening reaction is carried out under the action of tertiary butylamine to obtain the target compound I32, wherein the reaction temperature is 25-30 ℃, and the reaction solvent is acetone. Spectroscopic data for compound I32 of interest: 1 H NMR(600MHz,CDCl 3 ):δ＝8.44(dd,1H), 7.84(dd,1H),7.60(s,1H),7.42(d,1H),7.36(q,1H),7.24(d,1H),6.14(s,1H),1.32 (s,9H)； 13 C NMR(150MHz,CDCl 3 ):δ＝166.33,157.64,149.27,146.72,138.77, 138.37,137.89,134.03,133.59,130.28,129.41,128.27,126.71,125.75,124.46, 111.82,52.72,47.61,32.36,28.32；MS(ESI)m/z 588.0(M+H) + ,calcd.for C 20 H 17 Br 2 Cl 2 N 5 O 2 m/z＝586.9.
example 13
Preparation of other compounds in example 1 the other compounds listed in the table can be conveniently prepared by reference to the basic synthetic method described in the above examples and by selecting different conventional chemical raw materials in combination with the structural features of the compounds described in table 1. Physicochemical analytical data for a portion of representative compounds in example 1 are as follows:
compound I33: 1 H NMR(600MHz,CDCl 3 ):δ＝9.69(s,1H),8.47(dd,1H),7.85(dd, 1H),7.48(d,1H),7.38-7.36(m,2H),7.24(d,1H),6.41(s,1H),2.80-2.76(m, 1H),0.85(q,2H),0.51(q,2H)； 13 C NMR(150MHz,CDCl 3 ):δ＝168.14,156.93, 149.06,146.85,138.91,138.03,135.79,134.21,133.44,130.96,129.23,128.34, 126.78,125.77,123.60,111.79,38.31,29.71,6.67；MS(ESI)m/z 572.0(M+H) + ,calcd. for C 19 H 13 Br 2 Cl 2 N 5 O 2 m/z＝570.9.
compound I106: 1 H NMR(600MHz,CDCl 3 ):δ＝9.17(s,1H),8.47(dd,1H),7.87 (dd,1H),7.40-7.37(m,2H),7.13(q,2H),6.15(s,1H),2.92(d,3H)；MS(ESI)m/z 530.0(M+H) + ,552.1(M+Na) + ,calcd.for C 17 H 11 Br 2 ClFN 5 O 2 m/z＝528.9.
compound I107: 1 H NMR(600MHz,CDCl 3 ):δ＝9.51(s,1H),8.46(dd,1H),7.86 (dd,1H),7.38(q,1H),7.30(dd,1H),7.25(s,1H),7.09(dd,1H),6.21(t,1H), 3.39-3.35(m,2H),1.13(t,3H)；MS(ESI)m/z 544.0(M+H) + ,calcd.for C 18 H 13 Br 2 ClFN 5 O 2 m/z＝542.9.
compound I109: 1 H NMR(600MHz,CDCl 3 ):δ＝9.56(s,1H),8.47(dd,1H),7.86 (dd,1H),7.39-7.37(m,2H),7.25-7.24(m,1H),7.03(dd,1H),6.40(s,1H),2.80-2.76 (m,1H),0.85-0.83(m,2H),0.51-0.48(m,2H)； 13 C NMR(150MHz,CDCl 3 ):δ＝ 168.10,159.42,157.23,149.05,146.85,138.95,138.05,136.58,129.26,128.46, 128.33,125.80,124.09,122.04,121.88,114.12,113.96,111.70,23.24,6.67；MS(ESI) m/z 556.2(M+H) + ,calcd.for C 19 H 13 Br 2 ClFN 5 O 2 m/z＝554.9.
compound I161: 1 H NMR(600MHz,CDCl 3 ):δ＝9.78(s,1H),8.45(dd,1H),7.84 (dd,1H),7.49(d,1H),7.36(q,1H),7.31(d,1H),7.28(s,1H),6.53(t,1H),3.53(q, 2H),3.44(t,2H),3.26(s,1H)； 13 C NMR(150MHz,CDCl 3 ):δ＝166.77,156.58, 149.09,146.84,138.86,138.30,135.44,134.30,133.18,131.35,129.14,128.27, 126.82,125.66,123.30,111.62,70.44,58.76,39.92；MS(ESI)m/z 589.9(M+H) + , calcd.for C 19 H 15 Br 2 Cl 2 N 5 O 3 m/z＝588.9.
example 14
Some of the compounds of example 1 were tested for insecticidal activity, with the test targets being cotton bollworm (Helicoverpa armigera) and aphid (Aphis craccivora Koch), respectively. The screening method for the cotton bollworms is a conventional artificial feed surface coating method, specifically adopts a 24-hole cell culture plate to carry out activity screening, adds 300 microliters of artificial feed into each hole, and adds 20 microliters of liquid medicine into each hole; the screening method for aphids is a conventional dipping method. The primary screening concentration of the screened liquid medicine is 500mg/L, the test result is compared with a blank control, the death rate is 0-30% according to different levels of statistics, the death rate is 30-50% and 3, the death rate is 50-70% and 5, the death rate is 70-90% and 7, and the death rate is 90-100% and 9.
The results of the compound test are shown in table 2 below (compound numbers in table 2 correspond to compound numbers in example 1):
table 2: biological Activity of Compounds
The data in Table 2 shows that the tested compounds have significant killing effect on the tested pests at the tested concentration, and the mortality rate of at least one pest reaches more than 70%; especially, the insecticidal effect of part of the compounds on cotton bollworms and aphids under the test concentration reaches more than 90 percent. The results show that the discovery of the amide derivative containing the 3-bromo-5-chloro (fluoro) phenyl unit is possible to be one of means for solving the resistance of the existing pesticide, can be used as a substitute product in production practice, and also provides a technical strategy for the implementation of the reduction and synergy of the current pesticide.
Example 15
In combination with the activity screening situation of example 14, in order to further expand the application space of the compounds, I selected a part of the compounds for insecticidal activity test against tea geometrid (Ectropis oblique Prout), a main pest of tea trees. The specific screening method is a conventional leaf dipping feeding method, the primary screening concentration of the screened liquid medicine is 40mg/L, six times of repetition are carried out, the test result is compared with a control (positive pair and clear water), data statistics is carried out on the test result and the control (positive pair and clear water) respectively after 3 days of medicine, the death number of test insects is recorded, then the lowest and highest numerical values are removed respectively, and the death rate is calculated through statistical analysis.
The results of the compound test are shown in table 3 below (compound numbers in table 3 correspond to compound numbers in example 1):
table 3: control effect of compound on tea geometrid
The data in Table 3 show that part of the tested compounds have good control effect on tea geometrid under the test concentration, are better than positive control medicaments (Kangbian), and can be used as alternative products in the comprehensive control process of tea tree pests.
Example 16
The use of said amide derivatives containing 3-bromo-5-chloro (fluoro) phenyl units for the manufacture of pesticides. The typical amide derivative containing 3-bromo-5-chloro (fluoro) phenyl unit or its agropharmaceutically acceptable salt in example 1 was dissolved in a diluent to obtain an insecticide, and the insecticide contained various concentrations ranging from 0.001 to 99.99% by weight, preferably 5 to 25% by weight of the amide derivative containing 3-bromo-5-chloro (fluoro) phenyl unit or its salt. Wherein the diluent is one or more of 1, 2-dichloroethane, 1, 2-dibromoethane, xylene, isopropanol, glycerin, chlorobenzene, toluene, methanol, ethanol, propanol, N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, acetone, butanone, cyclohexanone and the like, and paraffin; or one or more of white carbon black, kaolin, talcum, diatomaceous earth, montmorillonite, bentonite, clay, activated clay, dolomite, quartz, calcium carbonate, oxide film and silica magnesia; or one or more of lignosulfonate, alkyl sulfonate, alkylaryl sulfonate, sorbitol polyoxyethylene ester, polyoxyethylene-fatty alcohol ether, polyoxyethylene-fatty acid ester, aralkyl polyethylene glycol ether, fluoroalkyl sulfonate, alkyl sulfate, polyethylene glycol and rhamnolipid; or one or more of polyvinyl alcohol, carboxymethyl cellulose and acacia; or one or more of inorganic dye, organic dye and trace nutrient.
The obtained pesticide is used as an active ingredient for preparing a pesticide or an insecticide for killing main biological pests such as cotton bollworms, plutella xylostella, tea geometrid, ash geometrid, tea caterpillar, tea leaf roller moth, tea leafhopper, tea pattern moth, tea thrips, tea leaf beetle, tea horn thorn leaf beetle, lygus lucorum, cnaphalocrocis medinalis, aphids, plant hoppers, white flies, prodenia litura, tobacco noctuid, tobacco aphid, armyworms, chilo suppressalis, tryporyza, bean pod borers, root knot nematodes, asian corn borers, soybean borers, peach fruit borers, vermilion spider mites, citrus red mites, two-spotted spider mites, culex light and the like.
The specific formulation of the pesticide can be prepared into conventional preparations such as aqueous emulsion, suspending agent, wettable powder, water dispersible granule and the like.
Claims (10)
1. An amide derivative which is a compound represented by the formula (I),
wherein:
R 1 one selected from the following groups:
R 2 and R is 3 Each independently is t-Bu, -CH 2 CH 2 OCH 3 、-CH 2 COCH 3 、-NH 2 、
X is chlorine or fluorine.
2. The amide derivative according to claim 1, having a structure of one of the following:
3. the process for producing an amide derivative according to claim 1, comprising the steps of: (i) The substituted anthranilic acid compound (1) is taken as a raw material, and an intermediate bromo-anthranilic acid compound (2) is prepared through bromination reaction; (ii) The bromo-anthranilic acid compound (2) and the substituted carboxylic acid (3) undergo a heterocyclic reaction under the action of methanesulfonyl chloride and an alkaline catalyst to obtain a heterocyclic intermediate substituted benzoxazinone (4); (iii) The substituted benzoxazinone (4) is subjected to ring opening under the action of substituted amine (5) to obtain an amide derivative (I);
wherein the base is triethylamine, pyridine or potassium carbonate;
the anthranilic acid compound (1), the bromo-anthranilic acid compound (2), the substituted carboxylic acid (3), the substituted benzoxazinone (4) and the substituted amine (5) and the reaction formula occurring in the preparation process are as follows:
4. a method of preparation according to claim 3, characterized in that: in the step (i), the reaction temperature is 0-45 ℃, and the reaction solvent is 1, 2-dichloroethane, dichloromethane, acetonitrile, tetrahydrofuran, ethyl acetate, acetone, N-dimethylacetamide, N-dimethylformamide or acetic acid, and the brominating reagent is bromine, dibromohydantoin or N-bromosuccinimide.
5. A method of preparation according to claim 3, characterized in that: in the step (ii), the reaction temperature is 20-50 ℃, and the reaction solvent is 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, dichloromethane, acetone or ethyl acetate.
6. A method of preparation according to claim 3, characterized in that: in the step (iii), the reaction temperature is 10-60 ℃, and the reaction solvent is diethyl ether, acetonitrile, tetrahydrofuran, dichloromethane, chloroform, dioxane, acetone or ethyl acetate.
7. An insecticide comprising the amide derivative of claim 1 and a diluent;
wherein the weight percentage of the amide derivative is 0.001-99.99%;
the diluent is one or more of dimethylbenzene, chlorobenzene, toluene, 1, 2-dichloroethane, 1, 2-dibromoethane, methanol, ethanol, propanol, isopropanol, glycerol, N-dimethylformamide, ethyl acetate, acetone, butanone, cyclohexanone, dimethyl sulfoxide and paraffin; or one or more of kaolin, bentonite, clay, diatomite, montmorillonite, activated clay, dolomite, quartz, calcium carbonate, oxide film, talcum and attapulgite; or one or more of alkyl sulfonate, alkylaryl sulfonate, sorbitol polyoxyethylene ester, polyoxyethylene-fatty alcohol ether, polyoxyethylene-fatty acid ester, aralkyl polyethylene glycol ether, fluoroalkyl sulfonate, alkyl sulfate, lignin sulfonate, polyethylene glycol and rhamnolipid; or one or more of polyvinyl alcohol, carboxymethyl cellulose and acacia; or one or more of inorganic dye, organic dye and trace nutrient.
8. The insecticide of claim 7, wherein: the weight percentage of the amide derivative is 5-25%.
9. The insecticide of claim 7, which is an aqueous emulsion, a suspension, a wettable powder, or a water dispersible granule.
10. Use of an amide derivative according to claim 1, or an insecticide according to claim 7, for combating biological pests such as cotton bollworms, plutella xylostella, tea geometrid, ash geometrid, tea caterpillar, leaf roller, tea leafhopper, tea moth, tea thrips, tea lism, tea leaf beetle, green plant bug, cnaphalocrocis medinalis, aphids, plant hoppers, white flies, prodenia litura, tobacco noctuid, tobacco aphid, armyworms, chilo suppressalis, trytis, bean pods, root knot nematodes, asian corn borers, soybean borers, peach borers, cinnabarines, citrus red spiders, spider mites, and culex lactuca.
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| WO2009121288A1 (en) * | 2008-04-01 | 2009-10-08 | 中国中化集团公司 | A preparation method of phenylcarboxamides |
| CN106928183A (en) * | 2015-12-29 | 2017-07-07 | 沈阳中化农药化工研发有限公司 | The preparation method of pyridyl pyrazoles alkanone carboxylic acid compound |
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| WO2009121288A1 (en) * | 2008-04-01 | 2009-10-08 | 中国中化集团公司 | A preparation method of phenylcarboxamides |
| CN106928183A (en) * | 2015-12-29 | 2017-07-07 | 沈阳中化农药化工研发有限公司 | The preparation method of pyridyl pyrazoles alkanone carboxylic acid compound |
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