CN103030574A

CN103030574A - Cyano acidamide compound, and synthetic method and application of compound

Info

Publication number: CN103030574A
Application number: CN2013100011711A
Authority: CN
Inventors: 袁德凯; 徐高飞
Original assignee: China Agricultural University
Current assignee: China Agricultural University
Priority date: 2013-01-04
Filing date: 2013-01-04
Publication date: 2013-04-10
Anticipated expiration: 2033-01-04
Also published as: CN103030574B

Abstract

The invention discloses a cyano acidamide compound, and a synthetic method and an application of the compound, and belongs to the technical field of organic compound synthesis. A structural formula of the cyano acidamide compound is as follows as shown in the specification. The synthetic method of the compound comprises the steps that intermediates of alpha-substituted carboxylic acid and alpha-aminopheny-lacetonitrile are synthesized, and then condensed according to a conventional condensation method, and the cyano acidamide compound is obtained. The compound can be used for preventing and treating cucumber gray mold, downy mildew, powdery mildew, puccinia sorghi, rice blast, mosquito larvae and the like. The synthetic method is reasonable and easy to operate, and the synthetized compound is novel in structure and large in potential modification and transformation room, can serve as a pesticide activity precursor structure for in-depth study, can serve as an agricultural bactericide, and has potential production and application values.

Description

Cyano-containing amide compounds and synthesis method and application thereof

Technical Field

The invention belongs to the technical field of organic compound synthesis, and particularly relates to a cyano amide-containing compound, and a synthesis method and application thereof.

Background

Plant fungal diseases and insect pests have great threat to agricultural production, and the occurrence of various plant diseases and insect pests causes huge loss every year.

Cyanation is one of the transformations common in organic synthesis and of significant practical value. Cyano is regarded as an important functional group and an effective active group to be paid more and more attention in the field of new pesticide creation, such as fipronil and chlorfenapyr which are high-efficiency insecticides, cyhalofop-butyl which is a herbicide, ethaboxam, cyanamide and azoxystrobin which are all playing an important role in agricultural production. With the progress of research, the cyano group is expected to make more recent progress in the field of compound design and synthesis, and from the aspect of application value, the cyano group derivative with more excellent performance and insecticidal, acaricidal, bactericidal or herbicidal activity is expected to be created.

Disclosure of Invention

The invention aims to provide a cyano-containing amide compound.

The invention also aims to provide a preparation method of the cyano amide-containing compound.

The invention also aims to provide application of the cyano amide compounds in preventing and treating agricultural diseases and insect pests.

A cyano-containing amide compound is characterized in that the compound has a structure shown in a general formula I:

wherein,

R₁is C_1-4Any one of alkyl groups of (a); preferably methyl or isopropyl;

R₂is any one of halogen, aryloxy and arylthio; preferably any one of a bromine atom, a phenoxy group and a 2, 4-dichlorophenoxy group; saidAryloxy is phenoxy or 2, 4-dichlorophenoxy;

R₃is any one of alkyl, alkoxy, hydroxyl, amino, nitro and halogen; preferably any one of alkyl, alkoxy and halogen;

the cyano-containing amide compounds are preferably:

n- (1-cyano-1-phenylethyl) -2-phenoxypropionamide, N- (1-cyano-1- (4-tolyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (4-methoxyphenyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (4-chlorophenyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (3-fluorophenyl) ethyl) -2-phenoxypropionamide, and mixtures thereof, N- (1-cyano-1- (4-bromophenyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (4-fluorophenyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (2, 4-dichlorophenyl) ethyl) -2-phenoxypropionamide, N- (1-cyano-1- (4-methylphenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1-phenylethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1- (4-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1- (3-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1- (3-fluorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1- (4-bromophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (1-cyano-1- (4-fluorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide, 2-bromo-N- (1-cyano-1- (4-methylphenyl) ethyl) -3-methylbutylamide, and salts thereof, 2-bromo-N- (1-cyano-1-phenylethyl) -3-methylbutyramide, 2-bromo-N- (1-cyano-1- (4-methoxyphenyl) ethyl) -3-methylbutyramide, 2-bromo-N- (1-cyano-1- (4-chlorophenyl) ethyl) -3-methylbutyramide, 2-bromo-N- (1-cyano-1- (3-fluorophenyl) ethyl) -3-methylbutyramide, 2-bromo-N- (1-cyano-1- (4-bromophenyl) ethyl) -3-methylbutyramide- 3-methylbutanamide, 2-bromo-N- (1-cyano-1- (4-fluorophenyl) ethyl) -3-methylbutanamide.

A preparation method of a cyano amide-containing compound comprises the following steps:

(1) using a compound shown in a general formula II as a raw material, and obtaining a compound shown in a general formula III through esterification and chlorination:

wherein R is₄Is methyl or ethyl;

(2) using a compound shown as a general formula IV as a raw material, and reacting the compound with a potassium hydroxide aqueous solution to obtain a compound shown as a general formula V:

(3) condensing a compound shown in a general formula V and a compound shown in a general formula III in N, N-dimethylformamide, and hydrolyzing to obtain a compound shown in a general formula VI:

wherein R is₅Is halogen;

(4) diazotizing an amino group by using a compound shown as a general formula VII as a raw material in the presence of nitrous acid, and substituting the amino group by halogen to obtain a compound shown as a general formula VIII:

(5) using a compound shown as a general formula VIII as a raw material, and reacting the compound with ammonia water and sodium cyanide to obtain a compound shown as a general formula IX:

(6) condensing the compounds shown in the general formulas VI and VII and the compound shown in the general formula IX in the presence of dichloromethane, DCC (dicyclohexylcarbodiimide) and DMAP (4-dimethylaminopyridine) to obtain the compound shown in the general formula I.

A cyano amide-containing compound (a compound shown in a general formula I) is applied to agricultural pest control: is used for preventing and treating cucumber gray mold, downy mildew, powdery mildew, corn rust, rice blast, mosquito larvae and the like.

The invention has the beneficial effects that:

the invention provides a cyano-containing compound with a brand-new structure, and finds that the compound has better bactericidal activity and insecticidal activity; the synthetic method of the compound provided by the invention is reasonable and easy to implement, the synthesized compound has a novel structure and a large scope for modification, can be used as a pesticide activity lead structure for deep research, can be possibly used as an agricultural bactericide for application, and has potential production and application values.

Detailed Description

The present invention is further illustrated in detail below with reference to specific examples:

example 1: n- (1-cyano-1-phenylethyl) -2-phenoxypropionamide

(1) Preparation of R-2-hydroxypropionic acid ethyl ester

In a 100mL three-mouth bottle provided with a return pipe, a water separator and a thermometerAdding 24mL (0.27mol) of absolute ethyl alcohol, 15g (0.11mol) of D-lactic acid, 33mL of benzene and 0.6mL of concentrated sulfuric acid, heating to 70 ℃, and maintaining the temperature for 4 hours until no water is separated out; with NaHCO₃Adjusting the pH value of the solution to 7; filtering, rectifying under normal pressure to remove benzene and ethanol, then distilling under reduced pressure, and collecting the distillate at 61-63 ℃ under 18mmHg to obtain colorless oily liquid with the yield of 88.4%.¹H-NMR：(300MHz，CDCl₃,ppm)：4.30-4.21(m，3H)，2.96(s，1H),1.42(d,3H,J＝6.93Hz),1.30(t，3H，J＝7.14Hz)。

(2) Preparation of ethyl S-2-chloropropionate

A100 mL three-necked flask equipped with a dropping funnel, a condenser tube and a tail gas absorber was charged with 10g (0.1mol) of ethyl R-2-hydroxypropionate and 0.1g of dried pyridine, and then the temperature was raised to 60 ℃ and SOCl was added dropwise₂11.09g (0.11mol), reacted for 9 h; then cooling and washing the mixture to be neutral by using saturated sodium bicarbonate solution; standing to obtain organic phase, washing the organic phase with water, drying with sodium sulfate, filtering, distilling under reduced pressure, collecting 74 deg.C fraction under 45mmHg to obtain 9.68g colorless liquid with yield 83.7%.¹H-NMR：(300MHz,CDCl₃,ppm)：4.39(q，1H，J＝6.93Hz)，4.24(q，2H，J=14.25Hz)，1.69(d，3H，J＝6.93Hz)，1.30(t，3H，J＝7.11Hz)。

(3) Preparation of Potassium Phenolate

31.1g (0.33mol) phenol and 50mL CCl₄Adding into a 250mL four-mouth bottle, dropwise adding 18.48g (0.33mol) of 20% potassium hydroxide aqueous solution under stirring, slightly releasing heat, turning the solution from red to brown, continuing stirring at room temperature for 5 minutes after the solution is added, then standing, and separating out an aqueous layer; the aqueous layer was concentrated to half of the original volume, cooled to precipitate brown crystals, filtered and dried in a desiccator for use.

(4) Preparation of R-2-phenoxypropionic acid ethyl ester

DMF as solvent, 5g (0.037mol) of ethyl S-2-chloropropionate and 5.8g (0.044mol) of potassium phenoxide react at 50 ℃ for 5 hours, the reaction solution is put into water with the volume 5 times that of the DMF, then ether is used for extraction, and then the extraction solution is dried and concentrated; using petroleum ether: ethyl acetate =10Column chromatography is carried out on the eluent of 1 to obtain colorless liquid with the yield of 64.3 percent.¹H-NMR：(300MHz,CDCl₃,ppm)：7.29-6.86(m，5H)，4.74(q,1H,J＝7.12Hz)，4.21(q，2H,J＝7.12Hz)，1.64-1.60(m，3H)，1.24(t,3H,J＝7.12Hz)。

(5) Preparation of R-2-phenoxypropionic acid

3.3g (0.017mol) of ethyl R-2-phenoxypropionate were dissolved in a mixture of 80mL of tetrahydrofuran and 80mL of water at room temperature, and 1.63g (0.068mol) of lithium hydroxide was added thereto with stirring to conduct a reaction at 50 ℃ for 5 hours. And (3) evaporating tetrahydrofuran, acidifying the water phase until the pH value is 1-2, separating out a white solid, and obtaining the yield of 84.6% at the temperature of m.p.104-106 ℃.¹H-NMR：(300MHz,CDCl₃,ppm)：9.13(s，1H)，7.32-7.25(m，2H)，7.02-6.88(m，3H),4.79(q，1H，J＝6.84Hz)，1.65(d，3H，J＝6.84Hz)。

(6) Preparation of 2-amino-2-phenylpropanenitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 18g (150mmol) of p-acetophenone were dissolved in 80mL of 50% aqueous ethanol solution, and 20mL of concentrated ammonia water was added under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, cooling, pouring the reaction mixture into 300mL of ice-water mixture, extracting with 3X 50mL of dichloroethane, washing the organic phase with 4X 50mL of water, drying with anhydrous magnesium sulfate, filtering, desolventizing, dissolving the residue in 150mL of anhydrous ether, introducing dry hydrogen chloride gas at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2-phenylpropionitrile hydrochloride, filtering, drying in vacuum, and storing at low temperature.

Dissolving 1.0g (5.4mmol) of 2-amino-2-phenylpropionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying the organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2-phenylpropionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1-phenylethyl) -2-phenoxypropionamide

0.75g (4.5mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and dicyclohexylcarbodiimide was added thereto under ice bath1.02g (4.95mmol) of amine (DCC), 0.604g (4.95mmol) of 4-Dimethylaminopyridine (DMAP), and a dichloromethane solution of 2-amino-2-phenylpropionitrile were added dropwise thereto, followed by reaction at room temperature with stirring for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, filtering to separate out a solid, concentrating the filtrate, and performing column chromatography purification (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.136-138 ℃, the yield is as follows: 57.14 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.45-6.88(m,11H),4.72(m,1H),1.96,1.93(ds,3H),1.61-1.55(m,3H)；MS(FAB⁺):293.0(M-H⁺)。

example 2: n- (1-cyano-1- (4-methylphenyl) ethyl) -2-phenoxypropionamide

(1) R-2-hydroxypropionic acid ethyl ester; (2) ethyl S-2-chloropropionate; (3) potassium phenolate; (4) r-2-phenoxypropionic acid ethyl ester; (5) the preparation of R-2-phenoxypropionic acid is the same as in example 1;

(6) preparation of 2-amino-2- (4-methylphenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 20g (150mmol) of p-methylacetophenone were dissolved in 80mL of an 50% aqueous ethanol solution, and 20mL of concentrated aqueous ammonia was added thereto under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is used for drying, filtering and desolventizing, the residue is dissolved in 150mL of anhydrous ether, and dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (4-methylphenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.1g (5.4mmol) of 2-amino-2- (4-methylphenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a dichloromethane solution of 2-amino-2- (4-methylphenyl) propionitrile for later use;

(7) preparation of N- (1-cyano-1- (4-methylphenyl) ethyl) -2-phenoxypropionamide

Taking R-0.75g (4.5mmol) of 2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC), 0.604g (4.95mmol) of DMAP (4-dimethylaminopyridine) and a dichloromethane solution of 2-amino-2- (4-methylphenyl) propionitrile were added dropwise under ice-cooling, followed by reaction at room temperature with stirring for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering again to separate out a solid, concentrating the filtrate, and purifying by column chromatography (V petroleum ether: V ethyl acetate =5:1) to obtain a white solid, wherein m.p.146-148 ℃, the yield is as follows: 61.87 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.37-6.84(m,10H),4.71(m,1H),2.36,2.34(ds,3H),1.96,1.93(ds,3H),1.61-1.55(m,3H)；MS(FAB⁺):331.0(M+Na⁺)。

example 3: n- (1-cyano-1- (4-methoxyphenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (4-methoxyphenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 22.5g (150mmol) of p-methoxyacetophenone were dissolved in 80mL of 50% ethanol aqueous solution, and 20mL of concentrated ammonia water was added under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is used for drying, filtering and desolventizing, the residue is dissolved in 150mL of anhydrous ether, and dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (4-methoxyphenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.3g (5.4mmol) of 2-amino-2- (4-methoxyphenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a dichloromethane solution of 2-amino-2- (4-methoxyphenyl) propionitrile for later use;

(7) preparation of N- (1-cyano-1- (4-methoxyphenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC), 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) and a dichloroethane solution of 2-amino-2- (4-methoxyphenyl) propionitrile were added dropwise under ice-cooling to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove precipitated solid, concentrating the filtrate, and performing column chromatography purification (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.158-160 ℃, the yield is as follows: 68.5 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.38-5.82(m,11H),4.73-4.67(m,1H),3.81,3.80(ds,3H),1.96,1.93(ds,3H),1.60-1.54(m,3H)；MS(FAB⁺):347.0(M+Na⁺)。

example 4: n- (1-cyano-1- (4-chlorophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (4-chlorophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 23g (150mmol) of p-chloroacetophenone were dissolved in 80mL of an 50% aqueous ethanol solution, followed by addition of 20mL of concentrated aqueous ammonia under stirring and reaction at 65 ℃ for 8 hours. After the reaction, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is used for drying, filtering and desolventizing, the residue is dissolved in 150mL of anhydrous ether, dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (4-chlorphenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.4g (5.4mmol) of 2-amino-2- (4-chlorophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (4-chlorophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (4-chlorophenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC), 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) (4.4mmol) and a dichloroethane solution of 2-amino-2- (4-chlorophenyl) propionitrile were added dropwise under ice-cooling, followed by reaction at room temperature with stirring for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and purifying by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.154-156 ℃, the yield is as follows: 51.30 percent;¹H-NMR(300MHz,CDCl₃，ppm):7.39-6.90(m,10H),4.74-4.70(m,1H),1.91,1.90(ds,3H),1.67-1.53(m,3H)；MS(FAB⁺):327.0(M-H⁺)。

example 5: n- (1-cyano-1- (3-chlorophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (3-chlorophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 23g (150mmol) of m-chloroacetophenone were dissolved in 80mL of an 50% aqueous ethanol solution, followed by addition of 20mL of concentrated aqueous ammonia under stirring and reaction at 65 ℃ for 8 hours. After the reaction, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is used for drying, filtering and desolventizing, the residue is dissolved in 150mL of anhydrous ether, dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (3-chlorphenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.4g (5.4mmol) of 2-amino-2- (3-chlorophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (3-chlorophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (3-chlorophenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and then added with 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) dropwise to the solution in 2-amino-2- (3-chlorophenyl) propionitrile dichloroethane in ice bath to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and performing column chromatography purification (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.158-160 ℃, the yield is as follows: 63.4 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.42-6.91(m,10H),4.75-4.71(m,1H),1.90(s,3H),1.62-1.54(m,3H)；MS(FAB⁺):351.0(M+Na⁺)。

example 6: n- (1-cyano-1- (3-bromophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (3-bromophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 30g (150mmol) of bromoacetophenone were dissolved in 80mL of 50% aqueous ethanol solution, and 20mL of concentrated ammonia water was added under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is dried, filtered and desolventized, the residue is dissolved in 150mL of anhydrous ether, and dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (3-bromophenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.41g (5.4mmol) of 2-amino-2- (3-bromophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (3-bromophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (3-bromophenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and then added with 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) dropwise to the solution in dichloromethane of 2-amino-2- (3-bromophenyl) propionitrile in ice bath to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and purifying by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p. is 150-152 ℃, and the yield is as follows: 69.4 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.57-6.90(m,10H),4.75-4.68(m,1H),1.90(s,3H),1.64-1.52(m,3H)；MS(FAB⁺):395(M+Na⁺)。

example 7: n- (1-cyano-1- (4-bromophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (4-bromophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 30g (150mmol) of p-bromoacetophenone were dissolved in 80mL of 50% aqueous ethanol solution, and 20mL of concentrated ammonia water was added under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is dried, filtered and desolventized, the residue is dissolved in 150mL of anhydrous ether, and dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (4-bromophenyl) propionitrile hydrochloride, and the precipitate is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.41g (5.4mmol) of 2-amino-2- (4-bromophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (4-bromophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (4-bromophenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC), 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) and a dichloroethane solution of 2-amino-2- (4-bromophenyl) propionitrile were added dropwise under ice-cooling to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and performing column chromatography purification (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.184-186 ℃, the yield is as follows: 33.78%;¹H-NMR(300MHz,CDCl₃，ppm)：7.55-6.91(m,10H),4.74-4.72(m,1H),1.90(s,3H),1.59-1.53(m,3H)；MS(FAB⁺):394.9(M+Na⁺)。

example 8: n- (1-cyano-1- (4-fluorophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (4-fluorophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 20g (150mmol) of p-fluoroacetophenone were dissolved in 80mL of an 50% aqueous ethanol solution, and 20mL of concentrated aqueous ammonia was added thereto under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, the temperature is reduced, the reaction mixture is poured into 300mL of ice-water mixture, 3X 50mL of dichloroethane is extracted, 4X 50mL of water is used for washing an organic phase, anhydrous magnesium sulfate is dried, filtered and desolventized, the residue is dissolved in 150mL of anhydrous diethyl ether, and dried hydrogen chloride gas is introduced at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (4-fluorophenyl) propionitrile hydrochloride, and the mixture is filtered, dried in vacuum and stored at low temperature.

Dissolving 1.1g (5.4mmol) of 2-amino-2- (4-fluorophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (4-fluorophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (4-fluorophenyl) ethyl) -2-phenoxypropionamide

0.66g (4mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC), 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) and a dichloromethane solution of 2-amino-2- (4-fluorophenyl) propionitrile were added dropwise under ice-cooling to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and purifying by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.121-123 ℃, the yield is as follows: 41.9 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.36-6.87(m,10H),4.74-4.68(m,1H),1.93,1.92(ds,3H),1.61-1.53(m,3H)；MS(FAB⁺):311.0(M-H⁺)。

example 9: n- (1-cyano-1- (2, 4-dichlorophenyl) ethyl) -2-phenoxypropionamide

(6) preparation of 2-amino-2- (2, 4-dichlorophenyl) propionitrile

In a 250mL pressure bottle, 8.5g (172mmol) of sodium cyanide, 9.2g (172mmol) of ammonium chloride and 30g (150mmol) of 2, 4-dichloroacetophenone were dissolved in 80mL of 50% ethanol aqueous solution, and 20mL of concentrated ammonia water was added under stirring to react at 65 ℃ for 8 hours. After the reaction is finished, cooling, pouring the reaction mixture into 300mL of ice-water mixture, extracting with 3X 50mL of dichloroethane, washing the organic phase with 4X 50mL of water, drying with anhydrous magnesium sulfate, filtering, desolventizing, dissolving the residue in 150mL of anhydrous ether, introducing dry hydrogen chloride gas at 0 ℃ to generate a large amount of off-white precipitate which is 2-amino-2- (2, 4-dichlorophenyl) propionitrile hydrochloride, filtering, drying in vacuum, and storing at low temperature.

Dissolving 1.41g (5.4mmol) of 2-amino-2- (2, 4-dichlorophenyl) propionitrile hydrochloride in 20mL of dichloromethane, adding 10mL of 10% NaOH aqueous solution, stirring for 10min, separating, drying an organic phase for 3 hours by using anhydrous sodium sulfate, and filtering to obtain a 2-amino-2- (2, 4-dichlorophenyl) propionitrile dichloromethane solution for later use;

(7) preparation of N- (1-cyano-1- (2, 4-dichlorophenyl) ethyl) -2-phenoxypropionamide

0.58g (3.5mmol) of R-2-phenoxypropionic acid was dissolved in 20mL of dichloromethane, and then added with 0.85g (4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.5g (4mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and a solution of 2-amino-2- (2, 4-dichlorophenyl) propionitrile in dichloromethane was added dropwise to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and purifying by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.142-144 ℃, the yield is as follows: 54.33 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.81-6.90(m,9H),4.73-4.67(m,1H),2.15,2.09(ds,3H),1.59-1.52(m,3H)；MS(FAB⁺):385.1(M+Na⁺)。

example 10: n- (1-cyano-1- (4-methylphenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

(1) R-2-hydroxypropionic acid ethyl ester; (2) the preparation of ethyl S-2-chloropropionate is as in example 1;

(3) preparation of potassium 2, 4-dichlorophenolate

10g (0.06mol) of 2, 4-dichlorophenol and 20mL of CCl₄Adding into 250mL four-neck flask, adding dropwise 20% aqueous solution prepared from 3.44g (0.33mol) potassium hydroxide under stirring, slightly releasing heat, turning solution from red to brown, stirring at room temperature for 5 min, standing, separating water layer, and concentrating to obtain crude productHalf of the product was cooled to precipitate colorless crystals, which were filtered and dried in a desiccator to give 12g of colorless crystals in 97.32% yield.

(4) Preparation of R-2- (2, 4-dichlorophenoxy) propionic acid ethyl ester

5g (0.037mol) of S-2-chloropropionic acid ethyl ester and 8.1g (0.04mol) of 2, 4-dichlorophenol potassium react in 20mLDMF at 50 ℃, the reaction solution is put into water which is 5 times as much as DMF after the reaction is finished, and ethyl ether is extracted, dried and concentrated; performing column chromatography with petroleum ether/ethyl acetate to obtain light yellow liquid with yield of 92.7%.

(5) Preparation of R-2- (2, 4-dichlorophenoxy) propionic acid

0.88g (3.35mmol) of ethyl R-2- (2, 4-dichlorophenoxy) propionate was dissolved in a mixture of 10mL of tetrahydrofuran and 10mL of water, and 0.32g (13.4mmol) of lithium hydroxide was added thereto with stirring to react at 50 ℃ for 5 hours. And (3) evaporating tetrahydrofuran, acidifying the water phase until the pH value is 1-2, and separating out a white solid with the m.p.98-100 ℃ and the yield of 80.77%.¹H-NMR：(300MHz,CDCl₃，ppm)：7.39-6.79(m,3H),4.74(q,1H,J＝6.86Hz),1.68(d，3H,J＝6.86Hz)。

(6) Preparation of 2-amino-2- (4-methylphenyl) propionitrile preparation reference is made to example 2.

(7) Preparation of N- (1-cyano-1- (4-methylphenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

1.06g (4.5mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added to the solution in ice bath, and a dichloroethane solution of 2-amino-2- (4-methylphenyl) propionitrile was added dropwise thereto and reacted at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 166-168 ℃, yield: 65.3 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.44-6.84(m,8H),4.74-4.68(m,1H),2.37,2.35(ds,3H),2.01,1.98(ds,3H),1.66-1.57(m,3H)；MS(FAB⁺):399.0(M+Na⁺)。

example 11: n- (1-cyano-1-phenylethyl) -2- (2, 4-dichlorophenoxy) propanamide

(3) potassium 2, 4-dichlorophenol; (4) ethyl R-2- (2, 4-dichlorophenoxy) propionate; (5) r-2- (2, 4-dichlorophenoxy) propionic acid was prepared as in example 10;

(6) 2-amino-2-phenylpropanenitrile was prepared as in example 1;

(7) preparation of N- (1-cyano-1-phenylethyl) -2- (2, 4-dichlorophenoxy) propanamide

1.06g (4.5mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added to the solution in ice bath, and a dichloroethane solution of 2-amino-2-phenylpropionitrile was added dropwise to the solution and reacted at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.108-110 ℃, the yield is as follows: 36 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.56-6.84(m,9H),4.75-4.70(m,1H),2.02,1.99(ds,3H),1.67-1.56(m,3H)；MS(FAB⁺):385.0(M+Na⁺)。

example 12: n- (1-cyano-1- (4-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

(6) 2-amino-2- (4-chlorophenyl) propionitrile was prepared as in example 4;

(7) preparation of N- (1-cyano-1- (4-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

0.94g (4mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and then added with 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and a solution of 2-amino-2- (4-chlorophenyl) propionitrile in dichloromethane was added dropwise thereto to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (petroleum ether/ethyl acetate =5/1) to obtain a white solid, wherein m.p. 102-104 ℃, the yield: 49.7 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.50-6.84(m,8H),4.77-4.66(m,1H),1.98,1.97(ds,3H),1.66-1.57(m,3H)；MS(FAB⁺):419.0(M+Na⁺)。

example 13: n- (1-cyano-1- (3-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

(6) 2-amino-2- (3-chlorophenyl) propionitrile was prepared as in example 5;

(7) preparation of N- (1-cyano-1- (3-chlorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

0.94g (4mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and then added with 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and a solution of 2-amino-2- (3-chlorophenyl) propionitrile in dichloromethane was added dropwise thereto to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 114-116 ℃, yield: 47.8 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.49-6.85(m,8H),4.76-4.70(m,1H),1.97,1.98(ds,3H),1.67-1.56(m,3H)；MS(FAB⁺):419.0(M+Na⁺)。

example 14: n- (1-cyano-1- (3-bromophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propanamide

(6) 2-amino-2- (3-bromophenyl) propionitrile prepared as in example 6;

(7) preparation of N- (1-cyano-1- (3-bromophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propanamide

0.94g (4mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and then added with 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and a solution of 2-amino-2- (3-bromophenyl) propionitrile in dichloromethane was added dropwise thereto to react at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p.106-108 ℃, yield: 46.1 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.65-6.85(m,8H),4.78-4.68(m,1H),1.98,1.97(ds,3H),1.68-1.56(m,3H)；MS(FAB⁺):465(M+Na⁺)。

example 15: n- (1-cyano-1- (4-bromophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propanamide

(6) 2-amino-2- (4-bromophenyl) propionitrile prepared as in example 7;

(7) preparation of N- (1-cyano-1- (4-bromophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propanamide

0.82g (3.5mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and then added with 0.8g (3.85mmol) of Dicyclohexylcarbodiimide (DCC) and 0.47g (3.85mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and a solution of 2-amino-2- (4-bromophenyl) propionitrile in dichloromethane was added dropwise thereto and reacted at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p.176-178 ℃, yield: 33.1 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.52-6.84(m,8H),4.70-4.57(m,1H),1.98(s,3H),1.66-1.57(d，3H)；MS(FAB⁺):464.9(M+Na⁺)。

example 16: n- (1-cyano-1- (4-fluorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

(6) 2-amino-2- (4-fluorophenyl) propionitrile was prepared as in example 8;

(7) preparation of N- (1-cyano-1- (4-fluorophenyl) ethyl) -2- (2, 4-dichlorophenoxy) propionamide

0.94g (4mmol) of R-2- (2, 4-dichlorophenoxy) propionic acid was dissolved in 20mL of dichloromethane, and 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto under ice-cooling, and a dichloromethane solution of 2-amino-2- (4-fluorophenyl) propionitrile was added dropwise thereto, followed by reaction at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p.106-108 ℃, yield: 68.4 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.55-6.84(m,8H),4.75-4.68(m,1H),2.00,1.98(ds,3H),1.66-1.57(dd,3H)；MS(FAB⁺):403.0(M+Na⁺)。

example 17: 2-bromo-N- (1-cyano-1- (4-methylphenyl) ethyl) -3-methylbutanamide

(1) Preparation of S-2-bromo-3-methylbutyric acid

In a 1L four-necked flask, 75mL of toluene, 75mL of water, 40% HBr156mL (1.15mol) were added and stirred down to 0 ℃; adding 48.1g (0.41mol) of L-valine at one time, slowly raising the temperature to 3.5 ℃, cooling to-5 ℃, and dropwise adding 36.85g (0.54mol) of NaNO₂After the addition of water in 80mL of water over 6 hours, the solution turned dark brown, and after the addition of water, the reaction was continued at-5 ℃ for 3 hours, diluted with 125mL of toluene, and heated to 20 ℃ for 12 hours. The organic phase was separated, the aqueous phase was extracted with 150mL of toluene, the organic phases were combined and washed with 20% Na₂S₂O₃The solution was washed with 100mL of a 20% NaCl solution, then with 100mL of a 20% NaCl solution, the organic phase was desolventized and pumped to dryness. Obtaining 52g of light yellow solid with m.p.32-34 ℃ and 70% yield;

(2) 2-amino-2- (4-methylphenyl) propionitrile prepared as described in example 2;

(3) preparation of 2-bromo-N- (1-cyano-1- (4-methylphenyl) ethyl) -3-methylbutanamide

0.8g (4.4mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto in an ice bath, and a solution of 2-amino-2- (4-methylphenyl) propionitrile in dichloromethane was added dropwise thereto to conduct a reaction at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 188-190 ℃, yield: 58.04 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.45-6.96(m,5H),4.34-4.28(m,1H),2.40,2.39(ds,3H),2.00,1.99(ds,3H),1.08-1.01(dd,6H)；MS(FAB⁺):347.0(M+Na⁺)。

example 18: 2-bromo-N- (1-cyano-1-phenylethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2-phenylpropanenitrile was prepared as in example 1;

(3) preparation of 2-bromo-N- (1-cyano-1-phenylethyl) -3-methylbutanamide

0.8g (4.4mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto under ice-cooling, and a dichloromethane solution of 2-amino-2-phenylpropionitrile was added dropwise thereto and reacted at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 184-185 ℃, yield: 60 percent;¹H-NMR(300MHz,CDCl₃，ppm):7.55-7.05(m,6H),4.34-4.27(dd，1H),2.41-2.40(m,1H),1.99,1.98(ds,3H),1.08-1.02(m,6H)；MS(FAB⁺):331.0(M+Na⁺)。

example 19: 2-bromo-N- (1-cyano-1- (4-methoxyphenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (4-methoxyphenyl) propionitrile was prepared as in example 3;

(3) preparation of 2-bromo-N- (1-cyano-1- (4-methoxyphenyl) ethyl) -3-methylbutanamide

0.9g (5mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.13g (5.5mmol) of Dicyclohexylcarbodiimide (DCC) and 0.67g (5.5mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto in an ice bath, and a solution of 2-amino-2- (4-methoxyphenyl) propionitrile in dichloromethane was added dropwise thereto to conduct a reaction at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p.160-162 ℃, yield:42.6%；¹H-NMR(300MHz,CDCl₃，ppm)：7.49-6.93(m,5H),4.34-4.28(dd,1H),2.30(m,1H),2.00,1.99(ds,3H),1.08-0.93(m,6H)；MS(FAB⁺):339(M+H⁺)。

example 20: 2-bromo-N- (1-cyano-1- (4-chlorophenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (4-chlorophenyl) propionitrile prepared as described in example 4;

(3) 2-bromo-N- (1-cyano-1- (4-chlorophenyl) ethyl) -3-methylbutanamide

0.9g (5mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.13g (5.5mmol) of Dicyclohexylcarbodiimide (DCC) and 0.67g (5.5mmol) of 4-Dimethylaminopyridine (DMAP) were added to the solution in dichloromethane in an ice bath, followed by dropwise addition of a solution of 2-amino-2- (4-chlorophenyl) propionitrile in dichloromethane, followed by reaction at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 164-166 ℃, yield: 36.8 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.50-7.25(m,5H),4.27-4.23(m,1H),2.40-2.31(m,1H),1.92,1.91(ds,3H),1.05-0.95(m,6H)；MS(FAB⁺):342.9(M-H⁺)。

example 21: 2-bromo-N- (1-cyano-1- (3-chlorophenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (3-chlorophenyl) propionitrile prepared as described in example 5;

(3) preparation of 2-bromo-N- (1-cyano-1- (3-chlorophenyl) ethyl) -3-methylbutanamide

Dissolving 0.72g (4mmol) of S-2-bromo-3-methylbutyric acid in 20mL of dichloromethane, adding 0.91g (4.4mmol) of Dicyclohexylcarbodiimide (DCC) and 0.54g (4.4mmol) of 4-Dimethylaminopyridine (DMAP) in an ice bath, and dropwise adding 2-amino-substituted benzene2- (3-chlorophenyl) propionitrile in dichloromethane, and reacting at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p. 166-168 ℃, yield: 65 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.50-7.05(m,5H),4.35-4.29(dd,1H),2.44-2.36(m,1H),1.97,1.96(dd,3H),1.08-0.94(m,6H)；MS(FAB⁺):342.9(M-H⁺)。

example 22: 2-bromo-N- (1-cyano-1- (3-bromophenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (3-bromophenyl) propionitrile prepared as in example 6;

(3) 2-bromo-N- (1-cyano-1- (3-bromophenyl) ethyl) -3-methylbutanamide

0.8g (4.5mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto in an ice bath, and a solution of 2-amino-2- (3-bromophenyl) propionitrile in dichloromethane was added dropwise thereto and reacted at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, concentrating the filtrate, and performing column chromatography (petroleum ether/ethyl acetate =5/1) to obtain a white solid, wherein m.p. is 170-172 ℃, and the yield is as follows: 59.3 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.64-7.01(m,5H),4.29-4.27(dd,1H),2.43-2.37(m,1H),1.96(s,3H),1.08-0.95(m,6H)；MS(FAB⁺):386.9(M-H⁺)。

example 23: 2-bromo-N- (1-cyano-1- (4-bromophenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (4-bromophenyl) propionitrile prepared as in example 7;

(3) preparation of 2-bromo-N- (1-cyano-1- (4-bromophenyl) ethyl) -3-methylbutanamide

0.9g (5mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.13g (5.5mmol) of Dicyclohexylcarbodiimide (DCC) and 0.67g (5.5mmol) of 4-Dimethylaminopyridine (DMAP) were added to the solution in dichloromethane in an ice bath, followed by dropwise addition of a solution of 2-amino-2- (4-bromophenyl) propionitrile for 5 hours at ordinary temperature. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, wherein m.p.158-160 ℃, the yield is as follows: 47.7 percent;¹H-NMR(300MHz,CDCl₃，ppm)：7.58-7.12(m,5H),4.31-4.25(dd,1H),2.43-2.31(m,1H),1.95(s,3H),1.17-0.93(m,6H)；MS(FAB⁺):386.8(M-H⁺)。

example 24: 2-bromo-N- (1-cyano-1- (4-fluorophenyl) ethyl) -3-methylbutanamide

(1) S-2-bromo-3-methylbutyric acid was prepared as in example 17;

(2) 2-amino-2- (4-fluorophenyl) propionitrile prepared as in example 8;

(3) preparation of 2-bromo-N- (1-cyano-1- (4-fluorophenyl) ethyl) -3-methylbutanamide

0.8g (4.5mmol) of S-2-bromo-3-methylbutyric acid was dissolved in 20mL of dichloromethane, and then 1.02g (4.95mmol) of Dicyclohexylcarbodiimide (DCC) and 0.6g (4.95mmol) of 4-Dimethylaminopyridine (DMAP) were added thereto in an ice bath, and a solution of 2-amino-2- (4-fluorophenyl) propionitrile in dichloromethane was added dropwise thereto to conduct a reaction at room temperature for 5 hours. Filtering, removing the solvent under reduced pressure, adding ethyl acetate into the residue, standing overnight in a refrigerator, filtering to remove the precipitated solid, and concentrating the filtrate by column chromatography (V petroleum ether/V ethyl acetate =5/1) to obtain a white solid, m.p.160-162 ℃, yield: 55.86 percent;¹H-NMR(300MHz,CDCl₃，ppm):7.56-7.00(m,5H),4.35-4.29(dd,1H),2.44-2.36(m,1H),1.99,1.98(ds,3H),1.08-0.88(m,6H)；MS(FAB⁺):349.0(M+Na⁺)。

example 25: fungicidal Activity test for Compounds

According to the agricultural industry standard (NY/T1156.2-2006) of the people's republic of China, a hypha growth rate method is adopted for determination. The inhibitory activity of target compounds of the hypha growth rate of various plant pathogenic bacteria such as apple ring rot, cucumber botrytis cinerea, sclerotinia sclerotiorum, wheat gibberella, tomato early blight, potato late blight, rice sheath blight, phytophthora capsici, cucumber wilt, peanut brown spot pathogen and the like is determined, and the results are shown in table 1; some of the compounds were tested for bactericidal activity in vivo against downy mildew, powdery mildew, corn rust and rice blast, and the results are shown in Table 2.

TABLE-1: fungicidal Activity data for Compounds (plate method)

TABLE-2: in vivo bactericidal activity data for compounds

Example 26: insecticidal Activity test of Compounds

Selecting armyworm and mosquito larva as test objects, performing activity preliminary screening control on a target compound, and treating the selected test insects by using a target compound diluted solution: the concentration of armyworm treatment is 600ppm, the concentration of mosquito larva treatment is 5ppm, and the test method is carried out according to the national standard method. Armyworm was treated at a concentration of 600ppm and mosquito larvae at a concentration of 5ppm, with activities as given in table-3:

TABLE-3: initial screening active lethality rate of insecticide at 600ppm and 5ppm concentration

It can be seen from example 25 that the cyano-containing compounds provided by the invention have good inhibitory activity on cucumber botrytis cinerea, rape sclerotia and apple ring spot in the sterilization aspect, the highest inhibitory rate can reach 67.2% when the cucumber botrytis cinerea is killed at 50 μ g/mL, and the compounds also have certain inhibitory activity on other tested bacteria; in example 3, the inhibition rate of 400 mug/mL of powdery mildew reaches 100%, the inhibition rate of corn rust reaches 85%, the concentration is reduced to 100 mug/mL and 25 mug/mL, the inhibition rates of example 3 to powdery mildew are 65% and 60%, respectively, and the inhibition rate of 6.25 mug/mL still has 50%; example 15 the inhibition rate of 400 mug/mL to powdery mildew and corn rust disease reach 100%, when the concentration is reduced to 100 mug/mL and 25 mug/mL, the inhibition rate to powdery mildew is 70% and 40%, respectively; examples 14 and 16 had a good effect of inhibiting rice blast, and examples 12, 16 and 24 had a good effect of inhibiting downy mildew; in terms of insecticidal activity, these compounds generally show lethal activity against mosquito larvae at various concentrations, up to 70% at 5 ppm.

Claims

1. A cyano-containing amide compound is characterized in that the compound has a structure shown in a general formula I:

wherein,

R₁is C_1-4Any one of alkyl groups of (a);

R₂is any of halogen, aryloxy and arylthioOne kind of the material is selected; the aryloxy is phenoxy or 2, 4-dichlorophenoxy;

R₃is any one of alkyl, alkoxy, hydroxyl, amino, nitro and halogen.

2. The cyano-containing amide compound of claim 1, wherein R is₁Is methyl or isopropyl.

3. The cyano-containing amide compound of claim 1, wherein R is₂Is any one of a bromine atom, a phenoxy group and a 2, 4-dichlorophenoxy group.

4. The cyano-containing amide compound of claim 1, wherein R is₃Is any one of alkyl, alkoxy and halogen.

5. The cyano-containing amide compound of claim 1, wherein the cyano-containing amide compound is:

6. The preparation method of the cyano amide-containing compound in the claim 1, which is characterized by comprising the following steps:

(1) using a compound shown as a general formula II as a raw material, and obtaining a compound shown as a general formula III through esterification and chlorination:

wherein R is₄Is methyl or ethyl;

wherein R is₅Is halogen;

(6) condensing the compounds shown in the general formulas VI and VII and the compound shown in the general formula IX in the presence of dichloromethane, DCC and DMAP to obtain the compound shown in the general formula I.

7. The application of the cyano amide-containing compounds in agricultural pest control, which is characterized in that the cyano amide-containing compounds are used for controlling cucumber gray mold, downy mildew, powdery mildew, corn rust, rice blast and mosquito larvae.