CN102503876A - Bisamide derivative, preparation method for same and application thereof - Google Patents
Bisamide derivative, preparation method for same and application thereof Download PDFInfo
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- 0 *c(cccc1C(O2)=O)c1C2=O Chemical compound *c(cccc1C(O2)=O)c1C2=O 0.000 description 5
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Abstract
The invention relates to a bisamide derivative, a preparation method for the same and application thereof. The bisamide derivative is a compound represented by the general formula (I) in the original text, wherein R1 refers to H (hydrogen), halogen, cyan, nitryl, amino, acetamido, trifluoroacetamide radical, trifluoroacetamide radical, benzamido, para toluene sulfonate, para toluene oxygen acetamido or 2,4-dihalide phenoxyacetamide radical; R2 refers to C1-C5 alkyl, cyclopropane radical, five-membered or six-membered heterocyclic radical; m refers to 0, 1 or 2; n refers to 0 or 1; R3 refers to H, cyan, trifluoroacetyl, amino-acetyl, trifluoroacetamide radical acetyl, acetamido-acetyl, hydroxyl, guanidyl, amino sulfo-carbonyl, amino-acetyl sulfo-carbonyl, trifluoroacetamide radical sulfo-carbonyl or acetamido sulfo-carbonyl; R4 refers to H or methyl; R5 refers to H or methyl; R6 refers to H or methyl; R7 refers to H or methyl; and Ym refers to halogen, nitryl, C1-C6 alkyl, C1-C6 alkoxy, trifluoro-methyl, trifluoro-ethyoxyl or sevo-fluoro-isopropyl. By the aid of the bisamide derivative, drug resistance of an original compound is improved, insecticidal activity is improved, and production cost is reduced.
Description
Technical field
The present invention relates to the synthetic technology of agricultural chemical insecticide, particularly a kind of bisamide derivatives and preparation and application.
Background technology
The control of invertebrates insect is the core realm of pesticide science research all the time, and the generally use of sterilant makes most invertebrates insects obtain effective improvement.But since the continuous expansion in market and the resistance of insect, the work-ing life of medicine etc. problem and people to the pay attention to day by day of environment; Need scientists constantly to study, so develop more effectively, low cost, low toxicity, environmentally safe and have a not insecticide variety of the mode of action of the same race.
Phthalic diamide and adjacent formamido-benzamides (ryania acceptor class) verivate is effective sterilant of developing the control lepidoptera pest in recent years.For example, US2003/0229050, CN200780007591.3, CN200580006757.0 and CN200680035345.4 etc.
For designing the synthetic bioactive novel derivative of desinsection that has; And improve the sterilant resistance and reduce production costs; One type of bisamide analog derivative not seeing bibliographical information has been synthesized in design, and biological activity test shows that this analog derivative has very high insecticidal activity.
Summary of the invention
The object of the present invention is to provide a kind of bisamide derivatives and the preparation and application that can improve original compound resistance and raising insecticidal activity.
Bisamide derivatives provided by the invention has following general formula:
In the formula: R
1Be H, halogen, cyanic acid, nitro, amino, acetamido, trifluoroacetyl amido, tribromo-acetyl amido, benzoylamino, tolysulfonyl amido, to toluene acetamide oxide base or 2,4-phenyl-dihalide acetamide oxide base;
R
2Be C
1-C
5Alkyl, Trimetylene base, five yuan or hexa-member heterocycle base,
M is 0,1 or 2;
N is 0 or 1;
R
3Be H, cyanic acid, trifluoroacetyl group, glycyl, trifluoroacetyl amido ethanoyl, acetamido ethanoyl, hydroxyl, guanidine radicals, amino thiocarbonyl, glycyl thiocarbonyl, trifluoroacetyl amido thiocarbonyl or acetamido thiocarbonyl;
R
4Be H or methyl;
R
5Be H or methyl;
R
6Be H or methyl;
R
7Be H or methyl;
Ym is halogen, nitro, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, trifluoromethyl, trifluoro ethoxy or seven fluorine sec.-propyls;
In the definition of above-claimed cpd, no matter following substituting group is represented in the separately use or be used in the compound word of used term:
Halogen is fluorine, chlorine, bromine or iodine;
Alkyl is the straight or branched alkyl;
Heteroatoms is N in five yuan or the hexa-member heterocycle base, O or S;
The step that the preparation method of described bisamide derivatives comprises:
Bisamide derivatives (I) compound method one:
General formula I V compound and general formula V compound (mol ratio is 1: 1) are dissolved in the acetate, and reaction made target compound II in 0.5-12 hour under boiling point; General formula I I compound and compound of formula III (mol ratio is 1: 1) are dissolved in the organic solvent, add an amount of acid or alkali then, react under the boiling point and make target compound I in 0.5-48 hour for-10 ℃ in temperature; Each group is like above-mentioned definition (R in the reaction formula
2Except, R
2Be C
1-C
5Straight chained alkyl or Trimetylene base).
Described organic solvent is selected from methylene dichloride, chloroform, tetracol phenixin, benzene,toluene,xylene, hexanaphthene, normal hexane, ETHYLE ACETATE, THF, 1,4-dioxane, N, dinethylformamide or DMSO 99.8MIN..
Described acid (acid and general formula I I compound mol ratio 0.001-0.1: 1) be selected from: methylsulphonic acid, Phenylsulfonic acid, p-methyl benzenesulfonic acid, acetate, SULPHOSUCCINIC ACID ESTER, or hydrochloric acid, sulfuric acid or phosphoric acid.
Described alkali is selected from organic bases (alkali and general formula I I compound mol ratio 0.001-0.1): triethylamine, pyridine, 1; 8-diaza-dicyclo (5; 4; O) undecylene-7 or N, accelerine, or mineral alkali: sodium hydroxide, Pottasium Hydroxide, yellow soda ash, salt of wormwood, sodium methylate, sodium tert-butoxide or potassium tert.-butoxide.
Bisamide derivatives (I) compound method two:
General formula I V compound and compound of formula III (mol ratio is 1: 1) are dissolved in the organic solvent, add an amount of organic bases then, are-10 ℃ in temperature and under boiling point, react 0.5-48 hour, add the appropriate amount of acid acidifying then and make target compound VI; General formula VI compound is dissolved in the organic solvent, adds an amount of organic bases and methylsulfonyl chloride (methylsulfonyl chloride and compound VI mol ratio are 1: 1) then, reacts below 10 ℃ in temperature to make target compound VII in 0.5-6 hour; General formula VII compound and general formula V compound (mol ratio is 1: 1) are dissolved in the organic solvent, add an amount of organic bases then, react under the boiling point and make target compound I in 0.5-48 hour for-10 ℃ in temperature; Each group is like above-mentioned definition in the reaction formula
Described organic solvent is selected from methylene dichloride, chloroform, tetracol phenixin, benzene,toluene,xylene, hexanaphthene, normal hexane, ETHYLE ACETATE, THF, 1,4-dioxane, N, dinethylformamide or DMSO 99.8MIN..
Described acid (acid and general formula I I compound mol ratio 0.001-0.1: 1) be selected from: methylsulphonic acid, Phenylsulfonic acid, p-methyl benzenesulfonic acid, acetate, SULPHOSUCCINIC ACID ESTER, or hydrochloric acid, sulfuric acid, phosphoric acid.
Described organic bases (alkali and general formula I I compound mol ratio 0.001-0.1): triethylamine, pyridine, 1,8-diaza-dicyclo (5,4, O) undecylene-7 or N, accelerine.
General formula I V compound can prepare through following method:
The 3-nitrophthalic acid generates diazonium salt with nitrite reaction under the mineral acid condition, react below 10 ℃ in temperature with general formula VIII compound to make target compound IX in 0.5-12 hour again; General formula I X compound and diacetyl oxide (mol ratio is 1: 4) temperature be 25 ℃ under the boiling point reaction made general formula compound IV in 0.5-48 hour; Each group is hydrochloric acid, sulfuric acid or phosphoric acid etc. like above-mentioned the described mineral acid of definition in the reaction formula.
Bisamide derivatives of the present invention is used to prepare agricultural chemical insecticide, especially for oriental armyworm, and the control of insects such as small cabbage moth and beet armyworm.
The salt that described bisamide derivatives or its are suitable on agricultural, or its steric isomer is used to prepare agricultural chemical insecticide.
Described bisamide derivatives is as the pesticide composition of activeconstituents and agriculture acceptable auxiliary agent composition, as sterilant.
New type double amide derivatives provided by the invention has very high insecticidal activity.Not only improved original compound resistance, also improved insecticidal activity and reduced production cost.
Embodiment
Further specify the present invention below in conjunction with embodiment, its objective is that can better understand content of the present invention is to embody substantive distinguishing features of the present invention, the example of therefore being lifted should not be regarded as the restriction to protection domain of the present invention.
Embodiment 1
N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 21) synthetic:
Steps A: preparation 3-iodo phthalic acid
With water (100mL), 3-nitrophthalic acid (21.10g, 0.1mol) and sodium hydroxide (9.2g 0.23mol) mixes; Ice-water bath stirs 30min, adds 2g Iron(III) chloride hexahydrate and 8g activated carbon, stirs and is warming up to 70 ℃; Slowly drip 80% Hydrazine Hydrate 80 (12.5g; 0.2mol), keep 70 ℃ to continue reaction to no longer producing till the bubble, reaction is accomplished.The suction filtration 3-aminophthalic acid sodium solution that obtains filtrating, cryosel is bathed cooling, adds Sodium Nitrite (10.4g; 0.15mol), treat that temperature drops to below 0 ℃, slowly dripping 60g concentration is 98% vitriol oil; Reaction solution becomes faint yellow turbid solution; Drip to finish, slowly drip again liquor kalii iodide (25g, 0.15mol).Insulation reaction 3h.Slowly be warming up to 50 ℃ then, continuation reaction 2-3h adds Sodium Thiosulfate Pentahydrate at last, stirs, and adds 300mL ETHYLE ACETATE, and water layer is removed in extraction, precipitation, and vacuum-drying gets yellow solid 3-iodo phthalic acid.
Step B: preparation 3-iodo Tetra hydro Phthalic anhydride
3-iodo phthalic acid (29.2g, 0.1mol) and diacetyl oxide (30mL) be mixed in the 100mL round-bottomed flask, heat little boil the reaction 2h, the decompression slough solvent, column chromatography gets faint yellow solid 3-iodo Tetra hydro Phthalic anhydride.
Step C: preparation 2-iodo-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM
In the 100mL single necked round bottom flask, add 3-iodo Tetra hydro Phthalic anhydride (2.74g; 10mmol) and methylene dichloride (30mL); Slowly drip under the room temperature be dissolved with 1-methylthio group-2-methyl-2-aminopropane (1.19g, 10mmol) and triethylamine (1.00g, 30mL dichloromethane solution 10mmol).After dripping off, reaction mixture stirring reaction 12h pours in the water; The Hydrogen chloride acidifying, water layer is with methylene dichloride (2 * 30mL) extractions, anhydrous sodium sulfate drying; Decompression is sloughed solvent and is got yellow solid 2-iodo-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM.
Step D: preparation 2-methyl-4-sevoflurane isopropyl amine
(1.07g 10mmol) is dissolved in the mixed solvent of 20ml water and 20ml MTBE, stirs to add seven fluorine isopropyl iodides (3.8g down successively with Ortho Toluidine; 13mmol), and V-Brite B (vat powder) (2.2g, 13mmol); Sodium hydrogencarbonate (1.1g; 13mmol) and 4-butyl ammonium hydrogen sulfate (0.4g 1.2mmol), stirred under the room temperature 8 hours.Separate organic phase, water layer is used the 30ml extracted with diethyl ether, merges organic phase, and organic phase is used 2molL successively
-1Hydrogen chloride, saturated sodium bicarbonate, the saturated common salt washing, anhydrous sodium sulfate drying, solvent is sloughed in decompression, gets colourless oil liquid 2-methyl-4-sevoflurane isopropyl amine.
Step e: preparation N-(1,1-dimethyl--2-methylmercaptoethyl)-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide
In the 100mL single necked round bottom flask, add 2-iodo-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM (1.97g, 5mmol) with methylene dichloride (15mL), under the ice bath slowly dropping be dissolved with triethylamine (0.50g; 10mL dichloromethane solution 5mmol) drips off the back and stirs 15min, keeps temperature to drip below 5 ℃ and is dissolved with methylsulfonyl chloride (0.57g; 10mL dichloromethane solution 5mmol), reaction mixture is stirring reaction 2h in ice bath, and TLC detects to reacting completely; Slowly drip then and be dissolved with 2-methyl-4-sevoflurane isopropyl amine (1.38g, 10mL dichloromethane solution 5mmol), room temperature reaction 2h after dripping off; TLC detects to reacting completely, and Hydrogen chloride (30mL) is washed, and saturated sodium bicarbonate (30mL) is washed; Saturated sodium-chloride (30mL) is washed, anhydrous sodium sulfate drying, and solvent is sloughed in decompression; Column chromatography gets white solid N-(1,1-dimethyl--2-methylmercaptoethyl)-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Step F: preparation N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide
With N-(1,1-dimethyl--2-methylmercaptoethyl)-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1, (0.65g is 1mmol) with single cyanogen ammonia (0.063g for 2-benzene first diamide; 1.5mmol) being dissolved in the 20mL acetonitrile, cryosel is bathed down and is stirred 30min, drips 10% chlorine bleach liquor (1.17g), and cryosel is bathed stirring reaction 1h down; Be warming up to 5 ℃ of reaction 1h, TLC detects to reacting completely, and pours in the water; (solvent is sloughed in decompression to ETHYLE ACETATE for 2 * 60mL) extractions, anhydrous sodium sulfate drying; Column chromatography gets white solid N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 2
N-[1,1-dimethyl--2-(S-methyl-N-aminocarboxyl thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 22) synthetic:
With N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (0.69g; 1mmol) and trifluoroacetic acid (0.34g 3mmol) is dissolved in the 20mL methylene dichloride, room temperature reaction 3h; TLC detects to reacting completely, and saturated sodium bicarbonate (30mL) is washed, and saturated sodium-chloride (30mL) is washed; Anhydrous sodium sulfate drying, solvent is sloughed in decompression, and column chromatography gets white solid N-[1; 1-dimethyl--2-(S-methyl-N-aminocarboxyl thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 3
N-[1,1-dimethyl--2-(S-methyl-N-TFA base thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 23) synthetic:
With N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (0.69g; 1mmol) and trifluoroacetic anhydride (0.63g 3mmol) is dissolved in the 20mL methylene dichloride, room temperature reaction 5h; TLC detects to reacting completely, and saturated sodium bicarbonate (30mL) is washed, and saturated sodium-chloride (30mL) is washed; Anhydrous sodium sulfate drying, solvent is sloughed in decompression, and column chromatography gets white solid N-[1; 1-dimethyl--2-(S-methyl-N-TFA base thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 4
N-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) sulfoxide group ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 31) synthetic:
With metachloroperbenzoic acid (0.26g, 1.5mmol) and ethanol (10mL) put into the 100mL single necked round bottom flask, ice-water bath stirs 15min; (0 ℃ is stirred 20min for 1.24g, the 3mmol) aqueous solution to add 10mL salt of wormwood; Slowly drip 20mLN-[1,1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (0.69g; 1mmol) ethanolic soln drips and finishes stirring reaction 15min under the ice-water bath; TLC detects to reacting completely, and the 20mL vat powder aqueous solution is washed, ETHYLE ACETATE (3 * 40mL) extractions; Saturated sodium-chloride (60mL) aqueous solution is washed, anhydrous sodium sulfate drying, and decompression is sloughed solvent and is got white solid N-[1; 1-dimethyl--2-(S-methyl-N-cyanic acid thiocarbonyl) sulfoxide group ethyl]-3-iodo-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 5
3-amino-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 167) synthetic:
Steps A: preparation 3-nitrophthalic acid acid anhydride
The 3-nitrophthalic acid (21.1g, 0.1mol) and diacetyl oxide (30mL) be mixed in the 100mL round-bottomed flask, heating reflux reaction 2h, decompression is sloughed solvent and is got faint yellow solid 3-nitrophthalic acid acid anhydride.
Step B: preparation 2-nitro-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM.
In the 100mL single necked round bottom flask, add 3-nitrophthalic acid acid anhydride (1.93g; 10mmol) and methylene dichloride (30mL); Slowly drip under the room temperature be dissolved with 1-methylthio group-2-methyl-2-aminopropane (1.19g, 10mmol) and triethylamine (1.00g, 30mL dichloromethane solution 10mmol).After dripping off, reaction mixture stirring reaction 12h pours in the water; The Hydrogen chloride acidifying, water layer is with methylene dichloride (2 * 30mL) extractions, anhydrous sodium sulfate drying; Decompression is sloughed solvent and is got yellow solid 2-nitro-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM.
Step C: preparation 3-nitro-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide
In the 100mL single necked round bottom flask, add 2-nitro-6-carboxy-N-(1,1-dimethyl--2-methylmercaptoethyl) BM (1.56g, 5mmol) with methylene dichloride (15mL), under the ice bath slowly dropping be dissolved with triethylamine (0.50g; 10mL dichloromethane solution 5mmol) drips off the back and stirs 15min, keeps temperature to drip below 5 ℃ and is dissolved with methylsulfonyl chloride (0.57g; 10mL dichloromethane solution 5mmol), reaction mixture is stirring reaction 2h in ice bath, and TLC detects to reacting completely; Slowly drip then and be dissolved with 2-methyl-4-sevoflurane isopropyl amine (1.38g, 10mL dichloromethane solution 5mmol), room temperature reaction 2h after dripping off; TLC detects to reacting completely, and Hydrogen chloride (30mL) is washed, and saturated sodium bicarbonate (30mL) is washed; Saturated sodium-chloride (30mL) is washed, anhydrous sodium sulfate drying, and solvent is sloughed in decompression; Column chromatography gets white solid 3-nitro-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Step D: preparation 3-amino-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide
With 3-nitro-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (1.40g; 2mmol) be dissolved in 15ml ethanol, add a small amount of palladium carbon dust (0.14g), logical hydrogen; Stirring at room reaction 6h filters, and solvent is sloughed in decompression; Column chromatography gets white solid 3-amino-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 6
3-(2, the 4-dichloro)-benzene acetamide oxide base-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 174) synthetic:
With 2,4 dichlorophenoxyacetic acid (0.22g, 1mmol) and thionyl chloride (15ml) add the 50mL round-bottomed flask, mixture heating up refluxing and stirring reaction 3h, decompression is sloughed most of solvent and is got the thick product of acyl chlorides.With 20ml THF dissolving acyl chlorides bullion, slowly be added drop-wise under the ice bath and be dissolved with 3-amino-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1; In the tetrahydrofuran solution of the 20ml of 2-benzene first diamide, drip off 20min after, drip a small amount of diisopropyl ethyl amine; Reaction mixture rises to room temperature reaction 12h naturally, and TLC detects to reacting completely, and Hydrogen chloride (30mL) is washed; Saturated sodium bicarbonate (30mL) is washed, and saturated sodium-chloride (30mL) is washed anhydrous sodium sulfate drying; Solvent is sloughed in decompression, and column chromatography gets white solid 3-(2, the 4-dichloro)-benzene acetamide oxide base-N-(1; 1-dimethyl--2-methylmercaptoethyl)-and N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 7
3-(2, the 4-dichloro)-benzene acetamide oxide base-N-(1,1-dimethyl--2-methylsulfonic acid ethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 182) synthetic:
With 3-(2, the 4-dichloro)-benzene acetamide oxide base-N-(1,1-dimethyl--2-methylmercaptoethyl)-N '-(2-methyl-4-sevoflurane isopropyl base)-1; 2-benzene first diamide (0.20g, 0.3mmol) and methylene dichloride (20mL) add in the 50mL round-bottomed flask stirring reaction 10min; The adding metachloroperbenzoic acid (0.11g, 0.65mmol), stirring at room reaction 1h; Cross leaching filtrating, decompression is sloughed solvent and is got white solid 3-(2, the 4-dichloro)-benzene acetamide oxide base-N-(1; 1-dimethyl--2-methylsulfonic acid ethyl)-and N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 8
3-nitro-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 214) synthetic:
Steps A: preparation 2-(2-methyl-4-seven fluorine sec.-propyls) phenyl-4-nitro isoindole-1,3-diketone
In the 100mL single necked round bottom flask, add 3-nitrophthalic acid acid anhydride (1.93g, 10mmol), 2-methyl-4-sevoflurane isopropyl amine (2.76g, 10mmol) and acetate (40mL); Reaction mixture stirring heating backflow 4h, TLC detect to reacting completely, and solvent is sloughed in decompression; Column chromatography gets yellow solid and pours in the water; The Hydrogen chloride acidifying, water layer is with methylene dichloride (2 * 30mL) extractions, anhydrous sodium sulfate drying; Decompression is sloughed solvent and is got yellow solid 2-(2-methyl-4-seven fluorine sec.-propyls) phenyl-4-nitro isoindole-1,3-diketone.
Step B: preparation 3-nitro-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide
With 2-(2-methyl-4-seven fluorine sec.-propyls) phenyl-4-nitro isoindole-1, and the 3-diketone (0.45g, 1mmol), salt of wormwood (10mg) and THF (20mL) join the 50mL round-bottomed flask; Stir 10min, slowly drip cyclopropylamine (0.057g, 1mmol) solution that is dissolved in the 10mL THF under the room temperature; Reaction mixture stirs 6h, and TLC detects to reacting completely, and solvent is sloughed in decompression; Add the 30mL methylene dichloride, Hydrogen chloride (30mL) is washed, and saturated sodium bicarbonate (30mL) is washed; Saturated sodium-chloride (30mL) is washed, anhydrous sodium sulfate drying, and solvent is sloughed in decompression; Column chromatography gets white solid 3-nitro-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 9
3-amino-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 216) synthetic:
With 3-nitro-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1, (1.14g 2mmol) is dissolved in 30ml methyl alcohol to 2-benzene first diamide; Add a small amount of palladium carbon dust (0.114g), logical hydrogen, 60 ℃ of following stirring reaction 2h; TLC detects to reacting completely, and filters, and solvent is sloughed in decompression; Column chromatography gets white solid 3-amino-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 10
3-iodo-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 215) synthetic:
With 3-amino-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1, (0.477g 1mmol) is dissolved in the 20mL20% Hydrogen chloride 2-benzene first diamide, and cryosel is bathed down; (0.138g, 10mL aqueous solution 2mmol) are incubated about 0 ℃ and react 2h slowly to drip Sodium Nitrite; Add 0.1g urea, continue reaction 15min, drip potassiumiodide (0.199g; 1.2mmol) the 10mL aqueous solution, after dripping off, rise to stirring at room reaction 2h naturally; TLC detects to reacting completely methylene dichloride (3 * 30mL) extractions, anhydrous sodium sulfate drying; Solvent is sloughed in decompression, and column chromatography gets white solid 3-iodo-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 11
3-trifluoroacetyl amido-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 217) synthetic:
With 3-amino-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (0.477g, 1mmol) and triethylamine (15mL) add the 50mL round-bottomed flask;-78 ℃ of stirring reaction 20min slowly drip trifluoroacetic anhydride (0.252g, 1.2mmol) solution; After dripping off, rise to room temperature reaction 4h naturally, TLC detects to reacting completely; Reaction solution is poured in the water, methylene dichloride (3 * 30mL) extractions, anhydrous sodium sulfate drying; Solvent is sloughed in decompression, and column chromatography gets white solid 3-trifluoroacetyl amido-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
Embodiment 12
3-acetamido-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide (verivate 218) synthetic:
With 3-amino-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1; 2-benzene first diamide (0.477g; 1mmol) be dissolved in the 20mL diacetyl oxide, stirring at room reaction 10min produces a large amount of white solids; Cross and filter product 3-acetamido-N-Trimetylene base-N '-(2-methyl-4-sevoflurane isopropyl base)-1,2-benzene first diamide.
This analog derivative 01～250 of different raw materials preparation be will adopt at present according to the preparation method of embodiment 1～12, table 1a, table 1b, table 1c listed in.
The part verivate
1HNMR (BrukerAV400spectrometerusingtetramethylsilaneastheintern alstandard) data are listed table 2 in.
Table 1a
Table 1b
Table 1c
Table 2
Embodiment 13
Utilize verivate provided by the invention (01～250) to test, verify the insect evaluated biological activity:
Any verivate provided by the invention (01～250) is dissolved in solvent, water and tensio-active agent, is mixed into the homogeneous water, be diluted with water to any required concentration during use, tested object and testing method are following:
1) to the evaluated biological activity of oriental armyworm: supplying the examination insect is oriental armyworm (MythimnaseparataWalker), the normal population that indoor leaf of Semen Maydis is raised.Adopt leaf dipping method, dipping leaf of Semen Maydis in seedling stage is put into diameter 7cm petridish after drying in the solution that has configured, insert 4 instar larvaes, and each concentration repeats 3 times; Contrast is with acetone soln soaking maize leaf breeding grub; Viewing test result after 24 hours, 48 hours, 72 hours;
2) to the evaluated biological activity of small cabbage moth: supplying the examination insect is small cabbage moth 2 instar larvaes (Plutellaxylostella (L.)), is the normal population of indoor normal raising; Adopt leaf dipping method, in the solution that has configured, time 2--3 second, get rid of surplus liquid with tweezers dipping cabbage leaves; Each 1, totally 3 in each sample; After treating that soup is done, put into the long straight type of 10cm in vitro, insert 2 age diamondback moth larvae, build the mouth of pipe with gauze; To test to handle placing standard treated indoor, viewing test result after 24 hours, 48 hours, 72 hours;
3) to the evaluated biological activity of beet armyworm: supplying the examination insect is beet armyworm 3 instar larvaes (LaphygmaexiguaHubner), is the normal population of indoor normal raising; Adopt leaf dipping method, in the solution that has configured, time 2--3 second, get rid of surplus liquid with tweezers dipping cabbage leaves; Each 1, totally 3 in each sample; After treating that soup is done, put into diameter 7cm petridish, insert beet armyworm 3 instar larvaes, will test to handle placing standard treated indoor, viewing test result after 24 hours, 48 hours, 72 hours;
The test result of above-mentioned test is as shown in table 3.
Table 3
Mortality ratio grade in the table: the A level is 100%-90%; The B level is 90%-70%; The C level is 70%-50%; The D level is 50%-0%.
Claims (9)
1. bisamide derivatives is characterized in that having following structural formula:
In the formula:
R
1Be H, halogen, cyanic acid, nitro, amino, acetamido, trifluoroacetyl amido, tribromo-acetyl amido, benzoylamino, tolysulfonyl amido, to toluene acetamide oxide base or 2,4-phenyl-dihalide acetamide oxide base;
R
2Be C
1-C
5Alkyl, Trimetylene base, five yuan or hexa-member heterocycle base,
M is 0,1 or 2;
N is 0 or 1;
R
3Be H, cyanic acid, trifluoroacetyl group, glycyl, trifluoroacetyl amido ethanoyl, acetamido ethanoyl, hydroxyl, guanidine radicals, amino thiocarbonyl, glycyl thiocarbonyl, trifluoroacetyl amido thiocarbonyl or acetamido thiocarbonyl;
R
4Be H or methyl;
R
5Be H or methyl;
R
6Be H or methyl;
R
7Be H or methyl;
Ym is halogen, nitro, C
1-C
6Alkyl, C
1-C
6Alkoxyl group, trifluoromethyl, trifluoro ethoxy or seven fluorine sec.-propyls;
In the definition of above-claimed cpd, no matter following substituting group is represented in the separately use or be used in the compound word of used term:
Halogen is fluorine, chlorine, bromine or iodine;
Alkyl is the straight or branched alkyl;
Heteroatoms is N, O or S in five yuan or the hexa-member heterocycle base.
2. bisamide derivatives according to claim 1 is characterized in that:
R
1Be H, halogen, cyanic acid, nitro, amino, acetamido, trifluoroacetyl amido, tribromo-acetyl amido, benzoylamino, tolysulfonyl amido, to toluene acetamide oxide base or 2,4-phenyl-dihalide acetamide oxide base; R
2Be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl, the tertiary butyl, n-pentyl, isopentyl, Trimetylene base, furans, thiophene, pyrroles, pyrazoles, pyridine 、 oxazole 、 isoxazole, pyridazine,
R
3Be H, cyanic acid, trifluoroacetyl group, glycyl, trifluoroacetyl amido ethanoyl, acetamido ethanoyl, hydroxyl, guanidine radicals, amino thiocarbonyl, glycyl thiocarbonyl, trifluoroacetyl amido thiocarbonyl or acetamido thiocarbonyl; R
4-R
7Be H or methyl; Ym is halogen, nitro, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec.-butyl, the tertiary butyl, methoxyl group, trifluoromethyl, trifluoro ethoxy or seven fluorine sec.-propyls.
3. bisamide derivatives according to claim 1 is characterized in that:
R
1Be H, fluorine, chlorine, bromine, iodine, cyanic acid, nitro, amino, acetamido, trifluoroacetyl amido, tribromo-acetyl amido, benzoylamino, tolysulfonyl amido, to toluene acetamide oxide base or 2,4-phenyl-dihalide acetamide oxide base; R
2Be normal-butyl, n-pentyl, isopentyl, Trimetylene base, furyl, pyrryl, pyrazolyl 、 isoxazolyl,
R
3Be cyanic acid, trifluoroacetyl group, glycyl, trifluoroacetyl amido ethanoyl, acetamido ethanoyl, hydroxyl, guanidine radicals, amino thiocarbonyl, glycyl thiocarbonyl, trifluoroacetyl amido thiocarbonyl or acetamido thiocarbonyl; Ym is fluorine, nitro, methyl, methoxyl group, trifluoromethyl, trifluoro ethoxy or seven fluorine sec.-propyls.
4. the preparation method of the described bisamide derivatives of claim 1 is characterized in that comprising following step:
Bisamide derivatives (I) compound method one:
General formula I V compound and general formula V compound, mol ratio is 1: 1, is dissolved in the acetate, reaction made target compound II in 0.5-12 hour under boiling point; General formula I I compound and compound of formula III, mol ratio is 1: 1, is dissolved in the organic solvent, adds an amount of acid or alkali then, reacts under the boiling point and makes target compound I in 0.5-48 hour for-10 ℃ in temperature; Each group is shown in claim 1 in the reaction formula; R
2Except, R
2Be C
1-C
5Straight chained alkyl or Trimetylene base;
Bisamide derivatives (I) compound method two:
general formula I V compound and compound of formula III; Mol ratio is 1: 1; Be dissolved in the organic solvent; Add organic bases then; Be-10 ℃ in temperature and under boiling point, reacted 0.5-48 hour, add the appropriate amount of acid acidifying then and make target compound VI; General formula VI compound is dissolved in the organic solvent, adds organic bases and methylsulfonyl chloride then, and methylsulfonyl chloride and compound VI mol ratio are 1: 1, reacts below 10 ℃ in temperature to make target compound VII in 0.5-6 hour; General formula VII compound and general formula V compound, mol ratio is 1: 1, is dissolved in the organic solvent, adds an amount of organic bases then, reacts under the boiling point and makes target compound I in 0.5-48 hour for-10 ℃ in temperature; Each group is shown in claim 1 in the reaction formula.
5. preparation method according to claim 4; It is characterized in that described organic solvent is selected from methylene dichloride, chloroform, tetracol phenixin, benzene,toluene,xylene, hexanaphthene, normal hexane, ETHYLE ACETATE, THF, 1; 4-dioxane, N, dinethylformamide or DMSO 99.8MIN..
6. preparation method according to claim 4 is characterized in that described acid is selected from: methylsulphonic acid, Phenylsulfonic acid, p-methyl benzenesulfonic acid, acetate, SULPHOSUCCINIC ACID ESTER, or hydrochloric acid, sulfuric acid, phosphoric acid.
7. preparation method according to claim 4 is characterized in that described alkali is selected from organic bases: triethylamine, pyridine, 1,8-diaza-dicyclo (5,4, O) undecylene-7 or N, accelerine; Or mineral alkali: sodium hydroxide, Pottasium Hydroxide, yellow soda ash, salt of wormwood, sodium methylate, sodium tert-butoxide or potassium tert.-butoxide.
8. the salt that on agricultural, is suitable for of the arbitrary described bisamide derivatives of claim 1-3 or its, or its steric isomer is used to prepare agricultural chemical insecticide.
9. the arbitrary described bisamide derivatives of claim 1-3 is as the pesticide composition of activeconstituents and agriculture acceptable auxiliary agent composition, as sterilant.
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| CN103420884A (en) * | 2013-05-17 | 2013-12-04 | 南开大学 | Double-amide derivative with optical activity and geometrical isomerism, and preparation and application thereof |
| CN104402785A (en) * | 2014-09-26 | 2015-03-11 | 南开大学 | Novel bisamides derivative and preparation method and application thereof |
| CN107674009A (en) * | 2017-11-24 | 2018-02-09 | 常州沃腾化工科技有限公司 | The preparation method of fipronil bisamide intermediate |
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| CN103420884B (en) * | 2013-05-17 | 2015-12-02 | 南开大学 | There is bisamide derivatives and the preparations and applicatio of optical activity and rotamerism |
| CN104402785A (en) * | 2014-09-26 | 2015-03-11 | 南开大学 | Novel bisamides derivative and preparation method and application thereof |
| CN107674009A (en) * | 2017-11-24 | 2018-02-09 | 常州沃腾化工科技有限公司 | The preparation method of fipronil bisamide intermediate |
| JP2021519264A (en) * | 2018-04-03 | 2021-08-10 | コルテバ アグリサイエンス エルエルシー | Molecules with pesticide utility, related compositions and pest control methods |
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| CN108689877A (en) * | 2018-07-06 | 2018-10-23 | 浙江工业大学 | A kind of bisamide class compound and the preparation method and application thereof containing chiral carbon |
| CN108689877B (en) * | 2018-07-06 | 2021-08-03 | 浙江工业大学 | Chiral carbon-containing bisamide compound and preparation method and application thereof |
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| CN109020934B (en) * | 2018-07-30 | 2022-03-08 | 绍兴贝斯美化工股份有限公司 | Preparation method of intermediate containing halogenated benzene ring side chain flubendiamide structure |
| CN112778192A (en) * | 2019-11-06 | 2021-05-11 | 浙江省化工研究院有限公司 | Polyfluoroalkyl-containing isoindolinone benzamide derivatives, and preparation method and application thereof |
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