CN117430529A - 2-cyanoacrylate compound salt and preparation method and application thereof - Google Patents

2-cyanoacrylate compound salt and preparation method and application thereof Download PDF

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Publication number
CN117430529A
CN117430529A CN202311334607.9A CN202311334607A CN117430529A CN 117430529 A CN117430529 A CN 117430529A CN 202311334607 A CN202311334607 A CN 202311334607A CN 117430529 A CN117430529 A CN 117430529A
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acid
cyanoacrylate compound
ethyl
ether
salt
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马海军
吴宁捷
马忠华
曹庆亮
曹杨
时亚东
万宏剑
王洪雷
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JIANGSU PESTICIDE RESEARCH INSTITUTE CO LTD
Zhejiang Chemical Industry Research Institute Co Ltd
Zhejiang University ZJU
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JIANGSU PESTICIDE RESEARCH INSTITUTE CO LTD
Zhejiang Chemical Industry Research Institute Co Ltd
Zhejiang University ZJU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
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  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a 2-cyanoacrylate compound salt, a preparation method and application thereof, wherein the general formula of the 2-cyanoacrylate compound salt is shown as a formula (I), and compared with the 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl group of the 2-cyanoacrylate compound salt shown as the general formula (I)]The water solubility of the ethyl acrylate is obviously improved, and the high bactericidal activity on wheat scab is still maintained.

Description

2-cyanoacrylate compound salt and preparation method and application thereof
Technical Field
The invention belongs to the field of bactericides, and particularly relates to a 2-cyanoacrylate compound salt, a preparation method and application thereof.
Background
The 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] ethyl acrylate (code number is ZJS 178) is a cyanoacrylate compound, and has a protective effect and a therapeutic effect on diseases caused by fusarium. The chemical structural formula is as follows:
chinese patent CN202110105207.5 discloses that ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate has higher inhibitory activity on mycelium growth of gibberella pathogen, and the activity at the same concentration is superior to that of the control agent, cyanogen mycoester. Chinese patents CN202210813382.4, CN202210792944.1 and CN202210805610.3 respectively disclose compositions of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate and pyrrole, triazole and succinic acid dehydrogenase inhibitor bactericides, and show that the composition has synergistic effect after compounding, can not only improve bactericidal activity, but also delay the generation of drug resistance of germs.
However, the solubility of the ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate in water in the prior art is extremely small, so that the application efficacy in fields is affected, and the application of the ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate in the fields of water-soluble preparation development and the like is limited. Therefore, improving the solubility is of great importance.
Disclosure of Invention
The invention aims to: aiming at the defects existing in the prior art, the invention provides a 2-cyanoacrylate compound salt capable of improving water solubility and having high bactericidal activity and a preparation method thereof.
The invention also provides application of the 2-cyanoacrylate compound salt in preventing and treating fungal diseases.
The technical scheme is as follows: in order to achieve the above purpose, the present invention provides a 2-cyanoacrylate compound salt, wherein the general formula of the 2-cyanoacrylate compound salt is shown as formula (I):
wherein:
n is selected from any number from 0 to 3;
x is independently selected from hydroiodic acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, sulfurous acid, carbonic acid, citric acid, malic acid, lactic acid, boric acid, C 1 -C 20 Alkyl carboxylic acid, C 1 -C 20 Alkylsulfonic acid, X 1 To X 2 Any one of the acids of the structure shown,
wherein:
r is independently selected from hydrogen, C 1 -C 20 Alkyl, halogenated C 1 -C 20 Alkyl, C 3 -C 20 Cycloalkyl, halo C 3 -C 20 Cycloalkyl, C 1 -C 20 Alkoxy, halo C 1 -C 20 Alkoxy, C 1 -C 20 Alkylthio, halo C 1 -C 20 Alkylthio, halogen, nitro, cyano, hydroxy or mercapto,
m is an integer from 0 to 5.
Preferably, n is selected from any number from 0 to 2.
Preferably, n is selected from any number from 0.2 to 1.
Preferably, the X is independently selected from hydroiodic acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, sulfurous acid, carbonic acid, citric acid, malic acid, lactic acid, boric acid, C 1 -C 10 Alkyl carboxylic acid, C 1 -C 10 Alkylsulfonic acid, X 1 To X 2 Any one of the acids of the structure shown.
Preferably, the X is independently selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, sulfurous acid, carbonic acid, citric acid, malic acid, lactic acid, boric acid, C 1 -C 6 Alkyl carboxylic acid, C 1 -C 6 Alkylsulfonic acid, X 1 To X 2 Any one of the acids of the structure shown.
Preferably, the X is independently selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, sulfurous acid, carbonic acid, citric acid, malic acid, lactic acid, boric acid, C 1 -C 3 Alkyl carboxylic acid, C 1 -C 3 Alkylsulfonic acid, X 1 To X 2 Any one of the acids of the structure shown.
More preferably, the X is independently selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, carbonic acid, citric acid, malic acid, lactic acid, formic acid, acetic acid, propionic acid, methanesulfonic acid, benzoic acid, p-toluenesulfonic acid.
Preferably, the substituents R are independently selected from hydrogen, C 1 -C 10 Alkyl, halogenated C 1 -C 10 Alkyl, C 3 -C 10 Cycloalkyl, halo C 3 -C 10 Cycloalkyl, C 1 -C 10 Alkoxy, halo C 1 -C 10 Alkoxy, C 1 -C 10 Alkylthio, halo C 1 -C 10 Alkylthio, halogen, nitro, cyano, hydroxy or mercapto.
Preferably, the substituents R are independently selected from hydrogen, C 1 -C 6 Alkyl, halogenSubstitute C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, halo C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio, halo C 1 -C 6 Alkylthio, halogen, nitro, cyano, hydroxy or mercapto.
Preferably, the substituents R are independently selected from hydrogen, C 1 -C 3 Alkyl, halogenated C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo C 1 -C 3 Alkoxy, C 1 -C 3 Alkylthio, halo C 1 -C 3 Alkylthio, halogen, nitro, cyano, hydroxy or mercapto.
Preferably, m is an integer from 0 to 4.
Preferably, m is an integer from 0 to 3.
More preferably, m is an integer from 0 to 2.
The preparation method of the 2-cyanoacrylate compound salt comprises the following specific steps: the catalyst is prepared by reacting ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate with acid in a solvent at a certain temperature, wherein the reaction equation is as follows:
wherein the substituents X, n are as defined above.
Wherein the solvent is selected from any one of water, toluene, methylene chloride, dichloroethane, chloroform, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, methyl tetrahydrofuran, 1, 3-dioxan, 1, 4-dioxan, diethoxymethane, glyme, ethylene glycol dibutyl ether, diglyme, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, triglyme, acetonitrile, propionitrile, methyl acetate, ethyl acetate, butyl acetate, ethyl propionate, methanol, ethanol, isopropanol, benzyl alcohol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, triethylene glycol monomethyl ether, acetone, methyl ethyl ketone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, cyclohexanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide and N-methylpyrrolidone.
Preferably, the solvent is selected from at least one of toluene, dichloromethane, chloroform, diethyl ether, tetrahydrofuran, 1, 4-dioxane, acetonitrile, ethyl acetate, methanol, ethanol, isopropanol, acetone, N-dimethylformamide and dimethyl sulfoxide.
Further, the molar ratio of the ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate to the acid is 1:0.1 to 10.
Preferably, the molar ratio of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate to acid is 1:0.1 to 5; the reaction temperature of the 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] ethyl acrylate and the acid is between-20 and 100 ℃ and the reaction time is between 0.1 and 10 hours.
Preferably, the reaction temperature of the ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate and the acid is 0-100 ℃ and the reaction time is 0.1-5 hours.
The 2-cyanoacrylate compound salts represented by the general formula (I) provided by the present invention are typical compounds related to Table 1, but the typical compounds described in Table 1 do not limit the scope of the present invention.
TABLE 1
Wherein, compound 9 is one of X1, and compound 4 is one of X2.
The invention relates to application of 2-cyanoacrylate compound salt in preventing and treating fungal diseases.
The invention relates to application of a compound salt prepared by a preparation method of a 2-cyanoacrylate compound salt in preventing and treating fungal diseases.
The application of the 2-cyanoacrylate compound salt in preventing and treating fungal diseases comprises the following steps: the 2-cyanoacrylate salt is applied to the bacteria or the medium in which the bacteria grow to be controlled.
Further, the application of the 2-cyanoacrylate compound salt shown in the general formula (I) in preventing and controlling fungal diseases is that the 2-cyanoacrylate compound salt is used for preventing and controlling diseases caused by any one or more fungi of fusarium, blakeslea, camelina, aureobasidium, phytophthora, alternaria, rhizopus, coriolus, acremonium, alternaria, verticillium, aspergillus, rhizoctonia, aspergillus, erythrocpora, botrytis, rhizoctonia and Monascus.
Wherein, the application of the 2-cyanoacrylate compound salt shown in the general formula (I) in preventing and controlling fungal diseases, and the 2-cyanoacrylate compound salt is used for preventing and controlling any one disease of scab, rice blast, gray mold, anthracnose, bakanae disease, downy mildew and powdery mildew.
Preferably, the application of the 2-cyanoacrylate compound salt shown in the general formula (I) in the prevention and treatment of wheat scab is provided.
The application of the 2-cyanoacrylate compound salt in preparing the pesticide preparation for preventing and treating the fungal diseases comprises 0.001-99.99% of the 2-cyanoacrylate compound salt shown in the general formula (I) by weight percentage.
Further, when the pesticide preparation is used for sterilization, the application amount of the 2-cyanoacrylate compound salt in the pesticide preparation is 10-1000 g per hectare.
Further, the pesticide preparation can be formulated into emulsifiable concentrates, suspending agents, aqueous suspending agents, microemulsions, (aqueous) emulsions, powders, wettable powders, soluble powders, (water-dispersible) granules or capsules, and the like.
The pesticide preparation provided by the invention can further contain an agriculturally acceptable carrier besides 0.001-99.99% by weight of 2-cyanoacrylate compound salt shown in the general formula (I).
Further, the carrier may be a solid or a liquid. Suitable solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicate such as talc; magnesium aluminum silicate such as kaolinite, kaolin, montmorillonite and mica; white carbon black, calcium carbonate and light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylenediamine. The liquid carrier includes water and an organic solvent, which can also be used as an adjuvant or an anti-freezing additive when water is used as a solvent or diluent. Suitable organic solvents include aromatic hydrocarbons such as benzene, xylene, toluene, and the like; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, chloroform, methylene chloride, etc.; aliphatic hydrocarbons such as petroleum fractions, cyclohexane, light mineral oils; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, cyclohexanol, and the like; and their ethers and esters; also ketones, such as acetone, cyclohexanone, dimethylformamide and N-methyl-pyrrolidone.
Alternatively, the carrier may be a surfactant. Suitable surfactants may be emulsifiers, dispersants or wetting agents; may be ionic or nonionic. Nonionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty amines, and commercially available emulsifiers: agricultural emulsion 2201B, agricultural emulsion 0203B and agricultural emulsion 100 # Pesticide emulsion 500 # Pesticide emulsion 600 # Pesticide emulsion 600-2 # Agricultural emulsion 1601, agricultural emulsion 2201, agricultural emulsion NP-10, agricultural emulsion NP-15, and agricultural emulsion 507 # Pesticide milk OX-635, pesticide milk OX-622, pesticide milk OX-653, pesticide milk OX-667, and pesticide milk 36 # . The dispersing agent comprises sodium lignin sulfonate, nekal, calcium lignin sulfonate, methyl naphthalene sulfonic acid formaldehyde condensate and the like. The wetting agent is as follows: sodium lauryl sulfate, sodium dodecyl benzene sulfonate and alkaneSodium naphthalene sulfonate, and the like.
The invention also provides a sterilization method, which comprises the following steps: the 2-cyanoacrylate compound salt shown in the general formula (I) is applied to bacteria or a medium for growth of the bacteria to be controlled, and when the 2-cyanoacrylate compound salt shown in the general formula (I) is applied to the bacteria or the medium for growth of the bacteria to be controlled, the application amount is 10-1000 g per hectare.
The invention provides a 2-cyanoacrylate compound salt with a novel structure, wherein a novel candidate compound ZJS178 is modified to prepare various salts of ZJS178 with a novel structure, and the salts are characterized and activity measured.
The beneficial effects are that: compared with the prior art, the invention has the following advantages:
compared with the 2-cyanoacrylate compound salt shown in the general formula (I), the 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] ethyl acrylate provided by the invention has obviously improved water solubility, and meanwhile, has higher bactericidal activity on wheat scab.
Detailed Description
The invention will be further illustrated with reference to the following specific examples, without limiting the invention to these specific embodiments. It will be appreciated by those skilled in the art that the invention encompasses all alternatives, modifications and equivalents as may be included within the scope of the claims.
The experimental methods described in the examples, unless otherwise specified, are all conventional; materials, reagents and the like used in the examples are commercially available unless otherwise specified.
The pathogenic bacteria used in the invention are all wild strains, are common strains for various vegetables and fruits to be diseased, and can be separated or purchased.
Example 1
Preparation of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate hydrochloride (Compound 1)
Ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate (2 g,7.32 mmol) was dissolved in 20mL of ethanol, concentrated hydrochloric acid (0.73 mL,8.78 mmol) at a concentration of 12mol/L was slowly added dropwise, and the mixture was stirred at room temperature for 0.5h after the completion of the dropwise addition. The solid obtained after desolventizing was washed with ethyl acetate, filtered and dried to obtain 2.15g of a pure product in 94.7% yield.
1 H NMR(MeOD,400MHz)δ:7.75(d,J＝7.6Hz,2H,Ph-H),7.66-7.61(m,2H,Ph-H),4.20(q,J＝7.2Hz,2H,-CH 2 ),3.63(q,J＝7.2Hz,2H,-CH 2 ),3.25(s,3H,-CH 3 ),1.26(t,J＝7.2Hz,3H,-CH 3 ),1.14(t,J＝7.2Hz,3H,-CH 3 )。
Example 2
Preparation of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate sulfate (Compound 2)
Ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate (2 g,7.32 mmol) was dissolved in 20mL of methanol, concentrated sulfuric acid (0.60 mL,11.00 mmol) at 18.4mol/L was slowly added dropwise, and the mixture was stirred at room temperature for 0.5h after the completion of the dropwise addition. Most of the solvent was distilled off under reduced pressure, filtered, and the cake was washed with ethyl acetate and dried to give 2.62g of pure product in 96.5% yield.
1 H NMR(D 2 O,400MHz)δ:7.81(d,J＝8.8Hz,2H,Ph-H),7.69(d,J＝8.8Hz,2H,Ph-H),4.24(q,J＝7.2Hz,2H,-CH 2 ),3.65(q,J＝7.2Hz,2H,-CH 2 ),3.27(s,3H,-CH 3 ),1.27(t,J＝7.2Hz,3H,-CH 3 ),1.15(t,J＝7.2Hz,3H,-CH 3 )。
Example 3
Preparation of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate methylsulfonate (Compound 3)
Ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate (2 g,7.32 mmol) was dissolved in 20mL of ethanol, and methanesulfonic acid (0.77 g,8.05 mmol) was slowly added dropwise, and after the addition was heated to 50℃and stirred for 1h. The solid obtained after desolventizing was washed with ethyl acetate, filtered and dried to give 2.66g of a pure product with a yield of 98.7%.
1 H NMR(MeOD,400MHz)δ:7.78-7.74(m,2H,Ph-H),7.65-7.58(m,2H,Ph-H),4.20(q,J＝7.2Hz,2H,-CH 2 ),3.64(q,J＝7.2Hz,2H,-CH 2 ),3.25(s,3H,-CH 3 ),2.65(s,3H,-CH 3 ),1.26(t,J＝7.2Hz,3H,-CH 3 ),1.14(t,J＝7.2Hz,3H,-CH 3 )。
Example 4
Preparation of ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate p-toluenesulfonate (Compound 4)
Ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate (2 g,7.32 mmol) was dissolved in 20mL of methylene chloride, p-toluenesulfonic acid (1.26 g,7.32 mmol) was added, and after completion of the dropwise addition, the mixture was stirred at room temperature for 1h. The solid obtained after desolventizing was washed with ethyl acetate, filtered and dried to obtain 3.20g of a pure product with a yield of 99.8%.
1 H NMR(MeOD,400MHz)δ:7.75-7.73(m,2H,Ph-H),7.66-7.63(m,2H,Ph-H),7.60-7.56(m,2H,Ph-H)，7.19-7.17(m,2H,Ph-H)，4.20(q,J＝7.2Hz,2H,-CH 2 ),3.62(q,J＝7.2Hz,2H,-CH 2 ),3.25(s,3H,-CH 3 ),2.31(s,3H,-CH 3 ),1.26(t,J＝7.2Hz,3H,-CH 3 ),1.13(t,J＝7.2Hz,3H,-CH 3 ). Solubility test
Examples of the water solubility measurement using the compounds of the present invention are given below, and it should be noted that the present invention is not limited to the following examples.
Example 5
Test for measuring solubility in Water
The 2-cyanoacrylate salt prepared in examples 1, 2, 3 and 4 is added into distilled water in excess (saturated state), and the mixture is stirred at room temperature for 12 hr under sealed condition, and the mixture is left to stand to obtain supernatant and the concentration of the solution is determined by HPLC method. Liquid phase instrument model: high performance liquid chromatograph (LC-20A) from Shimadzu corporation; chromatographic column: a 250mm C18 column from Cosmosil; a detector: a Diode Array Detector (DAD); column temperature: 35.0 ℃; mobile phase: acetonitrile (60%) +pure water (40%); flow rate: 1.00mL/min.
The water solubility of the numbered compounds (2-cyanoacrylate salts prepared in examples 1, 2, 3 and 4, respectively) in Table 1 were measured according to the present invention, and it is shown that: the compound of the invention has good water solubility, the water solubility is obviously higher than that of 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] ethyl acrylate, and the 'mg/L' refers to each milligram of the compound per liter, and the specific table 1 is as follows:
TABLE 1
The 2-cyanoacrylate compound salt such as hydrochloride or sulfate prepared from the invention can remarkably improve the solubility of the compound ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate.
Preparation of the formulation
Examples 6 to 10 below give practical examples of processing and formulating several bactericide dosage forms using the 2-cyanoacrylate compound salt represented by the general formula (I) as an active ingredient, and it should be noted that the present invention is not limited to the following examples. In these formulation examples, all "%" refer to weight percent.
Example 6
Wettable powder formulation
According to the mass percentage, 10 percent of 2-cyanoacrylate compound salt shown in the general formula (I) and 5 percent of lignosulfonate (M q ) Uniformly mixing 1% of laurinol polyoxyethylene ether (JFC), 40% of diatomite and 44% of light calcium carbonate, and crushing to obtain wettable powder.
EXAMPLE 7
Emulsifiable concentrate formulation
According to the mass percentage, heating and stirring uniformly 10% of 2-cyanoacrylate compound salt shown in any formula (I), 5% of pesticide emulsion No. 500 (calcium salt), 5% of pesticide emulsion No. 602, 5% of N-methyl-2-pyrrolidone and 75% of dimethylbenzene to obtain the emulsifiable concentrate.
Example 8
Granule formulation
Uniformly mixing 5% of 2-cyanoacrylate compound salt shown in any formula (I), 1% of polyvinyl alcohol (PVA), 4% of sodium naphthalene sulfonate formaldehyde condensate (NMO) and 90% of clay according to mass percentage, crushing, adding 20 parts of water into 100 parts of the mixture according to parts by weight, kneading, preparing into particles with 14-32 meshes by using an extrusion granulator, and drying to obtain the granules.
Example 9
Water-dispersible granule formulation
According to the mass percentage, 20 percent of 2-cyanoacrylate compound salt shown in any formula (I), 4 percent of naphthalene sulfonate formaldehyde condensate, 1 percent of naphthalene sulfonate, 2 percent of white carbon black and 73 percent of kaolin are mixed and crushed, and then water is added for kneading, and the mixture is added into a granulator with a screen mesh with certain specification for granulation. And then drying and sieving (according to the screen range) to obtain the granular product.
Example 10
Aqueous suspension formulations
According to the mass percentage, 25% of 2-cyanoacrylate compound salt shown in any formula (I), 1% of fatty alcohol polyoxyethylene ether, 3% of rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, 1% of magnesium aluminum silicate, 0.4% of organic silicon defoamer, 5% of propylene glycol and deionized water (69.5%) are mixed uniformly in advance, and then added into a sand mill for sand milling, suspension mother liquor is obtained after filtration, and prepared xanthan gum (0.1%) aqueous solution is added for shearing and mixing uniformly.
Activity test
Examples of biological activity assays using the compounds of the invention are given below, it being noted that the invention is not limited to the following examples.
Example 11
Indoor Activity assay
And (3) determining the inhibitory activity of the compound to be tested on the test pathogenic bacteria by adopting a hypha growth rate method. The test pathogenic bacteria are inoculated onto a PDA plate with the diameter of 90mm, when the colony grows to be close to the edge of a culture dish, a puncher with the diameter of 5mm is used for punching a bacterial dish at 1/3 of the periphery of a fresh colony, and the bacterial dish is respectively transferred to the center of the pre-configured PDA plate containing a series of concentration gradient compounds (1-4) to be tested by an inoculating needle, and meanwhile, the bacterial dish is inoculated onto the PDA plate only containing the same amount of solvent to serve as a control. Culturing in a 25 deg.C incubator for 2-3 days, photographing when the colony of pathogenic bacteria in control group grows near the edge of 90mm dish, and measuring the diameter of the colony by crisscross method. Wherein the hypha growth inhibition ratio (MGIR) is calculated by the following formula, MGIR% = [ (C-N)/(C-5)]X 100%, where C is the colony diameter of the blank control group, N is the colony diameter of the positive control or treatment group, and 5 is the dish diameter. This experiment was repeated 2 times, 3 dishes each. Test pathogen was fusarium graminearum (fusarium asiaticum (strain No. 2021)), EC was calculated by inhibition MGIR 90 The test results are shown in Table 2 below:
TABLE 2
Wherein the active ingredient is the content of ZJS178 in the compound or salt.
The invention evaluates the in vitro bactericidal activity of part of compounds with the numbers shown in the table 1, and the results show that: the compound of the invention has good bactericidal activity and good inhibition effect on the gibberellic disease original bacteria, and mu g/mL refers to EC after ZJS178 is prepared into salt per microgram of active substance/milliliter 90 The value is still lower than that of ZJS178 original medicine, the activity is obviously improved, and the experiment proves that the specific salt prepared by the invention can obviously improve the solubility and can maintain and even improve the activity of ZJS 178.

Claims (10)

1. The 2-cyanoacrylate compound salt is characterized in that the general formula of the 2-cyanoacrylate compound salt is shown as the formula (I):
wherein:
n is selected from any number from 0 to 3;
x is independently selected from hydroiodic acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid, sulfurous acid, carbonic acid, citric acid, malic acid, lactic acid, boric acid, C 1 -C 20 Alkyl carboxylic acid, C 1 -C 20 Alkylsulfonic acid, X 1 To X 2 Any one of the acids of the structure shown,
wherein:
r is independently selected from hydrogen, C 1 -C 20 Alkyl, halogenated C 1 -C 20 Alkyl, C 3 -C 20 Cycloalkyl, halo C 3 -C 20 Cycloalkyl, C 1 -C 20 Alkoxy, halo C 1 -C 20 Alkoxy, C 1 -C 20 Alkylthio, halo C 1 -C 20 Alkylthio, halogen, nitro, cyanoA hydroxyl group or a mercapto group,
m is an integer from 0 to 5.
2. A method for preparing the 2-cyanoacrylate compound salt according to claim 1, which is characterized in that the specific method comprises the following steps: is prepared by the reaction of 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylic acid ethyl ester and acid in a solvent, wherein the reaction equation is as follows:
wherein the substituent X, n is as defined in claim 1.
3. The method for producing a 2-cyanoacrylate compound salt according to claim 2, wherein:
the solvent is selected from at least one of water, toluene, methylene chloride, dichloroethane, chloroform, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, methyltetrahydrofuran, 1, 3-dioxan, 1, 4-dioxan, diethoxymethane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether, acetonitrile, propionitrile, methyl acetate, ethyl acetate, butyl acetate, ethyl propionate, methanol, ethanol, isopropanol, benzyl alcohol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, triethylene glycol monomethyl ether, acetone, methyl ethyl ketone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, cyclohexanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide and N-methylpyrrolidone.
4. The method for producing a salt of a 2-cyanoacrylate compound according to claim 2, wherein the molar ratio of the ethyl 2-cyano-3-amino-3- [4- (N-ethyl-N-methylamino) phenyl ] acrylate to the acid is 1: 0.1-10, the reaction temperature is-20-120 ℃, and the reaction time is 0.1-10 hours.
5. Use of a salt of a 2-cyanoacrylate compound as claimed in claim 1 for controlling fungal diseases.
6. The use according to claim 5 for controlling fungal diseases, wherein the application process is: the 2-cyanoacrylate salt is applied to the bacteria or the medium in which the bacteria grow to be controlled.
7. The use of a 2-cyanoacrylate compound salt according to claim 5 for controlling fungal diseases, wherein the 2-cyanoacrylate compound salt is used for controlling diseases caused by any one or more fungi of fusarium, erysiphe, camelina, basidiomyces, phytophthora, alternaria, amycolatopsis, epicoccum, cercospora, aspergillus, aschersonia, botrytis, rhizoctonia and xanthomonas.
8. The use of 2-cyanoacrylate compound salts according to claim 5 for controlling fungal diseases, wherein the 2-cyanoacrylate compound salts are used for controlling any one of scab, rice blast, gray mold, anthracnose, bakanae disease, downy mildew and powdery mildew.
9. Use of a salt of a 2-cyanoacrylate compound according to claim 1 for the preparation of a pesticide formulation for controlling fungal diseases, wherein the pesticide formulation preferably comprises 0.001-99.99% by weight of the salt of the 2-cyanoacrylate compound.
10. A sterilization method, characterized in that the pesticide preparation of claim 9 is adopted for sterilization, wherein the application amount of 2-cyanoacrylate compound salt in the pesticide preparation is 10-1000 g per hectare.
CN202311334607.9A 2023-10-16 2023-10-16 2-cyanoacrylate compound salt and preparation method and application thereof Pending CN117430529A (en)

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