2-cyanoacrylate compound, preparation method and application thereof
阅读说明：本技术 一种2-氰基丙烯酸酯类化合物、其制备方法及应用 (2-cyanoacrylate compound, preparation method and application thereof ) 是由 吴宁捷 马忠华 侯廷军 许天明 唐广飞 富炜涛 于 2020-06-03 设计创作，主要内容包括：本发明公开了一种通式(I)表示的2-氰基丙烯酸酯类化合物：各取代基见说明书。本发明还公开了所述2-氰基丙烯酸酯类化合物的制备方法及用途,所述2-氰基丙烯酸酯类化合物用于防治真菌病害。(The invention discloses a 2-cyanoacrylate compound represented by a general formula (I):)
1. A2-cyanoacrylate compound represented by the general formula (I):
wherein:
X1、X2、X3、X4independently selected from hydrogen, C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C10Cycloalkyl, halo C3-C10Cycloalkyl radical, C1-C10Alkoxy, halo C1-C10Alkoxy radical, C2-C10Alkenyl radical, C2-C10Alkynyl, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C10An alkoxycarbonyl group;
Y1、Y2independently selected from hydrogen, C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C6Cycloalkyl, halo C3-C10Cycloalkyl radical, C1-C10Alkoxy, halo C1-C10Alkoxy, halogen, cyano, nitro, hydroxy, mercapto;
r is independently selected from hydrogen and C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C10Cycloalkyl, halo C3-C10Cycloalkyl radical, C2-C10Alkenyl radical, C2-C10Alkynyl, phenyl or the following R1To R3One of the structures shown:
wherein p is an integer of 1 to 10.
2. 2-cyanoacrylate-based compound according to claim 1, wherein: in the 2-cyanoacrylate compounds shown in the general formula (I):
X1、X2、X3、X4independently selected from hydrogen, C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C2-C6Alkenyl radical, C2-C6Alkynyl, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C6An alkoxycarbonyl group;
Y1、Y2independently selected from hydrogen, C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy, halogen, cyano, nitro, hydroxy, mercapto;
r is independently selected from hydrogen and C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, phenyl or R1To R3One of the structures shown:
wherein p is an integer of 1 to 6.
3. 2-cyanoacrylate-based compound according to claim 2, wherein: in the 2-cyanoacrylate compounds shown in the general formula (I):
X1、X2、X3、X4independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C3An alkoxycarbonyl group;
Y1、Y2independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, cyano, nitro, hydroxy, mercapto;
r is independently selected from hydrogen and C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl, phenyl or R1To R3One of the structures shown:
wherein p is an integer of 1 to 3.
4. A 2-cyanoacrylate-based compound according to claim 3, wherein: in the 2-cyanoacrylate compounds shown in the general formula (I):
X1、X2、X3、X4independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C3An alkoxycarbonyl group;
Y1、Y2independently selected from hydrogen, halogenPlain, hydroxyl, mercapto;
r is independently selected from hydrogen and C1-C3Alkyl, halo C1-C3Alkyl or R1To R2One of the structures shown:
wherein p is an integer of 1 to 2.
5. The 2-cyanoacrylate-based compound according to any one of claims 1 to 4, wherein: the 2-cyanoacrylate compound is of a cis structure or a trans structure.
6. 2-cyanoacrylate-based compound according to claim 1, wherein: the 2-cyanoacrylate compound shown in the general formula (I) is selected from at least one of the following compounds:
7. the process for producing a 2-cyanoacrylate compound represented by the general formula (I) according to any one of claims 1 to 6, wherein: the preparation method comprises the following steps:
wherein the catalyst is at least one selected from titanium tetrachloride, aluminum trichloride, boron trifluoride, zinc dichloride, ferric trichloride, ferric tribromide and stannic chloride;
the halogenating reagent is selected from at least one of chlorine, phosphorus trichloride, disulfide dichloride, N-chlorosuccinimide, bromine, hydrobromic acid, N-bromosuccinimide, dibromohydantoin, potassium fluoride, N-fluorobisbenzenesulfonamide or selective fluorine reagent;
the alkali is selected from at least one of 4-dimethylamino pyridine, piperidine, N-diisopropylethylamine, diethylamine, triethylamine and triethylene diamine;
the solvent is at least one selected from dichloromethane, trichloromethane, toluene, benzene, acetonitrile, acetone, N-dimethylformamide, tetrahydrofuran and dioxane.
8. Use of 2-cyanoacrylate compounds of general formula (I) according to any one of claims 1 to 6, characterized in that: the 2-cyanoacrylate compound is used for preventing and treating fungal diseases.
9. Use of a 2-cyanoacrylate-based compound according to claim 8, characterized in that: the 2-cyanoacrylate compounds are used for preventing and treating diseases caused by at least one of fusarium, erysiphe, camel rust, oblongella, phytophthora, alternaria, brussella, dermataceae, acrochaetomium, ustilago, melasma, aspergillus, ascochya, botrytis, rhizoctonia and xanthomonas.
10. Use of a 2-cyanoacrylate-based compound according to claim 8, characterized in that: the 2-cyanoacrylate compounds are used for preventing and treating at least one disease of gibberellic disease, rice blast, gray mold, anthracnose, bakanae disease, downy mildew and powdery mildew.
11. A pesticide formulation characterized by: the pesticide preparation contains 0.001-99.99 wt% of 2-cyanoacrylate compounds shown in the general formula (I) in any one of claims 1-6.
12. A sterilization method, characterized by: applying a 2-cyanoacrylate compound of formula (I) according to any one of claims 1 to 6 to a pathogen to be controlled or a medium for its growth.
13. The sterilization method according to claim 12, wherein: the application amount of the 2-cyanoacrylate compound is 10-1000 g per hectare.
Technical Field
The invention belongs to the field of bactericides, and particularly relates to a 2-cyanoacrylate compound and application thereof in preventing and treating fungal diseases.
Background
The 2-cyanoacrylate compounds not only have the medical activities of resisting tumors and the like, but also have the pesticide activities of weeding, resisting fungi, resisting plant viruses and the like, so that the 2-cyanoacrylate compounds are always valued in the field of pesticide preparation. For example, the fungicide variety phenamacril can effectively prevent and treat diseases such as wheat scab, rice bakanae disease and the like.
The patent CN1160318C of pesticide research institute in Jiangsu province discloses 2-cyano-3-substituted phenyl acrylate compounds shown in the following general formula (A), which can inhibit the growth of wheat scab germ hypha, thereby achieving the effect of preventing and treating wheat scab.
The patent CN109879834A of pesticide research institute of Jiangsu province also discloses 2-cyano-3-amino acrylate compounds shown in the following general formula (B), and the Mannich base bactericides can inhibit hypha growth and have control effect on plant diseases caused by fusarium such as wheat scab.
The patent CN109879841A of Jiangsu province pesticide research institute also discloses (Z) -3-imino-1-propenol compounds shown as the following general formula (C), which have excellent specific killing activity on fusarium causing plant diseases, such as wheat scab, cucumber anthracnose, cucumber fusarium wilt, peanut root rot, watermelon fusarium wilt, rice bakanae disease, mango anthracnose and other plant diseases caused by fusarium, and particularly can inhibit the growth of hypha and reduce the generation of wheat scab toxin (DON) at the same time of inhibiting the growth of the wheat scab.
It is understood that the above-mentioned publications are all achieved by inhibiting the growth of hyphae for the purpose of controlling fungal diseases such as wheat scab, and particularly acrylic ester compounds and acrylic alcohol compounds. However, as known to those skilled in the art, the growth of fungi includes two stages of spore germination and hypha growth, and the fungi can be inhibited from the spore germination stage to control fungal diseases with higher efficiency and better effect from the source.
Disclosure of Invention
In order to solve the above technical problems, the present invention provides a 2-cyanoacrylate compound represented by the following formula (I):
in the 2-cyanoacrylate compound, a double bond connected with a cyano group and an alkoxycarbonyl group can be in a Z-type or E-type configuration, namely, the 2-cyanoacrylate compound can be in a cis-type structure or a trans-type structure.
In the 2-cyanoacrylate compounds shown in the general formula (I) provided by the invention, X1、X2、X3、X4Independently selected from hydrogen, C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C10Cycloalkyl, halo C3-C10Cycloalkyl radical, C1-C10Alkoxy, halo C1-C10Alkoxy radical, C2-C10Alkenyl radical, C2-C10Alkynyl, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C10An alkoxycarbonyl group.
As a preferred mode, the substituent X1、X2、X3、X4Independently selected from hydrogen、C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy radical, C2-C6Alkenyl radical, C2-C6Alkynyl, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C6An alkoxycarbonyl group.
As a further preferred mode, the substituent X1、X2、X3、X4Independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C3An alkoxycarbonyl group.
As a still further preferred mode, the substituent X1、X2、X3、X4Independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, nitro, cyano, hydroxy, mercapto, carboxyl, C1-C3An alkoxycarbonyl group.
In the 2-cyanoacrylate compounds shown in the general formula (I) provided by the invention, Y1、Y2Independently selected from hydrogen, C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C6Cycloalkyl, halo C3-C10Cycloalkyl radical, C1-C10Alkoxy, halo C1-C10Alkoxy, halogen, cyano, nitro, hydroxy, mercapto.
As a preferred mode, the substituent Y1、Y2Independently selected from hydrogen, C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C6Alkoxy, halo C1-C6Alkoxy, halogen, cyano, nitro, hydroxy, mercapto.
In a further preferred embodiment, the substituent Y is1、Y2Independently selected from hydrogen, C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C1-C3Alkoxy, halo C1-C3Alkoxy, halogen, cyano, nitro, hydroxy, mercapto.
As a still further preferred mode, the substituent Y1、Y2Independently selected from hydrogen, halogen, hydroxyl, mercapto.
In the 2-cyanoacrylate compound shown in the general formula (I), R is independently selected from hydrogen and C1-C10Alkyl, halo C1-C10Alkyl radical, C3-C10Cycloalkyl, halo C3-C10Cycloalkyl radical, C2-C10Alkenyl radical, C2-C10Alkynyl, phenyl or the following R1To R3One of the structures shown:
as a preferred mode, the substituent R is independently selected from hydrogen and C1-C6Alkyl, halo C1-C6Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, phenyl or R1To R3One of the structures shown.
In a further preferred embodiment, the substituents R are independently selected from hydrogen and C1-C3Alkyl, halo C1-C3Alkyl radical, C3-C6Cycloalkyl, halo C3-C6Cycloalkyl, phenyl or R1To R3One of the structures shown.
As a further preferred mode, the substituents R are independently selected from hydrogen and C1-C3Alkyl, halo C1-C3Alkyl or R1To R2One of the structures shown.
R is as defined above1To R3In the structure, p is an integer of 1-10.
In a preferred embodiment, p is an integer of 1 to 6.
More preferably, p is an integer of 1 to 3.
In a more preferred embodiment, p is an integer of 1 to 2.
In a most preferred embodiment, the 2-cyanoacrylate compound represented by the above general formula (I) is at least one compound selected from the group consisting of compounds represented by the following structural formulae,
among the substituents described in the present invention: alkyl means straight or branched chain forms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like; cycloalkyl is meant to include cyclic chain forms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; alkenyl means straight or branched chain forms such as vinyl, 1-propenyl, allyl, isopropenyl, 1-butenyl, 1, 3-butadienyl, 1-hexenyl and the like; alkynyl refers to straight or branched chain forms, such as ethynyl, 1-propynyl, propargyl, 2-butynyl, 2-pentynyl, 3-hexynyl, and the like; haloalkyl refers to a group in which the alkyl group is substituted with one or more halogen atoms; alkoxy means a group having an oxygen atom attached to the end of an alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy, t-butoxy, etc.; haloalkoxy means a group in which an alkyl group is substituted with one or more halogen atoms and an oxygen atom is attached to the terminal; halogen means fluorine, chlorine, bromine, iodine.
When the double bond connected with the cyano and the alkoxycarbonyl is in a Z-type configuration, the 2-cyanoacrylate compound shown in the general formula (I) has the following structural formula (I-1),
the index Table 1 lists typical compounds represented by the structural formula (I-1), but the typical compounds described in the index Table 1 do not limit the scope of the present invention.
Index Table 1
The 2-cyanoacrylate compound shown in the general formula (I) has the following structural formula (I-2) when a double bond connected with a cyano group and an alkoxycarbonyl group is in an E-type configuration,
the index Table 2 lists typical compounds represented by the structural formula (I-2), but the typical compounds described in the index Table 2 do not limit the scope of the present invention.
Index table 2
The following table 3 is the nuclear magnetic data of some of the compounds described in index table 1 and index table 2. The compound numbers in table 3 correspond to the compound numbers in index table 1 and index table 2, i.e.: the compound No. 1 described in table 3 corresponds to the compound No. 1 described in the index table 1. In Table 3, s is singlet, d is doublet, dd is doublet, t is triplet, td is triplet, q is quartet, and m is multiplet.
TABLE 3 nuclear magnetic data of compounds
The invention also provides a preparation method of the 2-cyanoacrylate compound shown in the structural formula (I), firstly, ethyl cyanoacetate and substituted 1-indanone shown in the formula (II) are subjected to condensation reaction in an organic solvent in the presence of a catalyst and a dehydrating agent to prepare an intermediate shown in the formula (III), and then the intermediate shown in the formula (III) is subjected to reaction in the presence of a halogenating reagent and alkali in the organic solvent by a one-pot method of halogenation, elimination and the like or step-by-step preparation of the 2-cyanoacrylate compound shown in the structural formula (I):
the definitions of the substituents and their preferences are as described above.
In the preparation method, a catalyst, a halogenating agent, a base, a solvent and the like which are commonly used in the field can be used in the invention.
Preferably, the catalyst is selected from at least one of titanium tetrachloride, aluminum trichloride, boron trifluoride, zinc dichloride, iron trichloride, iron tribromide and tin tetrachloride; when Y is chlorine, the halogenating agent is at least one selected from chlorine, phosphorus trichloride, disulfide dichloride and N-chlorosuccinimide; when Y is bromine, the halogenating agent is at least one selected from bromine, hydrobromic acid, N-bromosuccinimide and dibromohydantoin; when Y is fluorine, the halogenating agent is selected from at least one of potassium fluoride, N-fluorobisbenzenesulfonamide and a selective fluorine agent (SELECTFLUOR); the alkali is selected from at least one of 4-dimethylamino pyridine, piperidine, N-diisopropylethylamine, diethylamine, triethylamine and triethylene diamine; the solvent is at least one selected from dichloromethane, trichloromethane, toluene, benzene, acetonitrile, acetone, N-dimethylformamide, tetrahydrofuran and dioxane.
The invention also provides an application of the 2-cyanoacrylate compound shown in the general formula (I), and the 2-cyanoacrylate compound shown in the general formula (I) is suitable for preventing and treating fungal diseases. The 2-cyanoacrylate compound is used for inhibiting spore germination of fungi, so that fungal diseases are prevented and treated.
When the 2-cyanoacrylate compound represented by the general formula (I) is used for controlling fungal diseases, the 2-cyanoacrylate compound represented by the general formula (I) is used for controlling diseases caused by at least one of fusarium, erysiphe, camelina, pedunculosis, phytophthora, alternaria, cladosporium, dermataceae, chaetomium, ustilago, polyspora, aspergillus, ascochyta, botrytis, rhizoctonia and xanthomonas.
When the 2-cyanoacrylate compound shown in the general formula (I) is used for preventing and treating fungal diseases, the 2-cyanoacrylate compound shown in the general formula (I) is used for preventing and treating at least one disease of gibberellic disease, rice blast, gray mold, anthracnose, bakanae disease, downy mildew and powdery mildew.
The invention also provides a pesticide preparation, which contains 0.001-99.99 wt% of the 2-cyanoacrylate compound shown in the general formula (I). The pesticide preparation can be prepared into missible oil, suspending agent, water suspending agent, microemulsion, (water) emulsion, powder, wettable powder, soluble powder, (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 the 2-cyanoacrylate compound shown in the general formula (I).
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 silicates such as talc; magnesium aluminum silicates such as kaolinite, montmorillonite and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylene diamine. Liquid carriers include water and organic solvents, which can also be used as adjuvants or antifreeze additives 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, dichloromethane, and the like; aliphatic hydrocarbons such as petroleum fractions, cyclohexane, light mineral oil; alcohols such as isopropyl alcohol, butyl alcohol, ethylene glycol, glycerin, cyclohexanol, and the like; and ethers and esters thereof; and also ketones, such as acetone, cyclohexanone, and dimethylformamide and N-methyl-pyrrolidone.
The carrier may also be a surfactant. Suitable surfactants may be emulsifying agents, dispersing agents or wetting agents; may be ionic or non-ionic. Nonionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty ammonia, and commercially available emulsifiers: nongru 2201B, Nongru 0203B and Nongru 100#Agricultural milk 500#Agricultural milk 600#Agricultural milk 600-2#1601, 2201, NP-10, NP-15 and 507#Agricultural milk OX-635 and agricultural milk OX-622. Agricultural milk OX-653, agricultural milk OX-667, Ningru 36#. The dispersant comprises sodium lignosulfonate, nekal, calcium lignosulfonate, methyl naphthalene sulfonic acid formaldehyde condensate and the like. The wetting agent is: sodium lauryl sulfate, sodium dodecylbenzenesulfonate, sodium alkylnaphthalenesulfonate, and the like.
The invention also provides a sterilization method, which comprises the following steps: applying the 2-cyanoacrylate compound shown in the general formula (I) to a pathogen needing to be controlled or a medium for growing the pathogen. When the 2-cyanoacrylate compound shown in the general formula (I) is applied to germs to be controlled or a medium for growing the germs, the application amount is 10-1000 g per hectare.
Detailed Description
The present invention is further illustrated by the following examples, which are not intended to limit the invention to these embodiments. It will be appreciated by those skilled in the art that the present invention encompasses all alternatives, modifications and equivalents as may be included within the scope of the claims.
Preparation of compounds
Example 1: synthesis of Compounds 20 and 124
Step 1: synthesis of intermediate 20a
1.09g of 4, 6-dichloro-1-indanone, 0.74g of ethyl cyanoacetate and 20mL of dichloromethane are added into a reaction bottle, 2.08g of titanium tetrachloride is slowly added dropwise under ice bath, and stirring is carried out for 30 minutes after the dropwise addition is finished. 0.3mL of pyridine was further added dropwise under ice bath, and after completion of the addition, the mixture was warmed to room temperature and stirred for 1 hour, and then 0.9mL of pyridine was added thereto and stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched with 3M aqueous hydrochloric acid, the organic phase was separated and the aqueous phase was extracted twice with dichloromethane. The organic phases were combined and passed over anhydrous Na2SO4After drying and concentration, 0.91g of a mixture 20a containing the Z and E configurations (brown solid, 56.5% yield) is obtained, and the crude product is directly taken to the next reaction without further purification.
Step 2: synthesis of Compounds 20 and 124
5.35g of dithio dichloride were slowly added dropwise to a tetrahydrofuran solution containing 1.30g of intermediate 20a, 2.84g N, N-diisopropylethylamine at-30 ℃. After the end of the dropwise addition, the temperature was raised to 0 ℃ and stirred for 24 hours. A tetrahydrofuran solution containing 2.94g N-chlorosuccinimide was added to the reaction solution, and the mixture was refluxed for 5 hours. After the reaction, the reaction mixture was filtered, and the filtrate was concentrated and then separated by column chromatography (eluent, ethyl acetate and petroleum ether, volume ratio: 1: 20) to obtain 0.50g Z-configured compound 20 (red solid, yield 31.3%) and 0.20g E-configured compound 124 (red solid, yield 12.8%), respectively.
Example 2: synthesis of Compounds 24 and 128
Step 1: synthesis of intermediate 24a
0.72g of 1-indanone, 0.74g of ethyl cyanoacetate and 20mL of dichloromethane were added to a reaction flask, 2.08g of titanium tetrachloride was slowly added dropwise in ice bath, and stirring was carried out for 30 minutes after the completion of the addition. 0.3mL of pyridine was further added dropwise under ice bath, and after completion of the addition, the mixture was warmed to room temperature and stirred for 1 hour, and then 0.9mL of pyridine was added thereto and stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched with 3M aqueous hydrochloric acid, the organic phase was separated and the aqueous phase was extracted twice with dichloromethane. The organic phases were combined and passed over anhydrous Na2SO4After drying and concentration, 1.01g of a mixture 24a containing the Z and E configurations (brown solid, 91.4% yield) is obtained, and the crude product is directly taken to the next reaction without further purification.
Step 2: synthesis of Compounds 24 and 128
0.50g of intermediate 24a, 2.35g N-bromosuccinimide, 0.49g of triethylenediamine, and 50mL of tetrahydrofuran were added to a reaction flask, and stirred at room temperature for 24 hours. After the reaction was completed, 10% aqueous sulfuric acid was added and extracted twice with dichloromethane. The organic phases were combined and passed over anhydrous Na2SO4After drying, concentration and separation by column chromatography (eluent ethyl acetate and petroleum ether in a volume ratio of 1: 20) gave 0.24g Z (red solid, yield 28.8%) and 0.09g E (red solid, yield 10.9%) of compound 24 (red solid) respectively.
Secondly, preparation of the preparation
Practical examples of the formulation of several fungicide formulations using the compound (I) of the present invention as an active ingredient are given in examples 3 to 7 below, it being noted that the present invention is not limited only to the scope of the following examples. In these formulation examples, all "%" refer to weight percent.
Example 3 wettable powder formulation
15% of Compound (I) (index Table 1 and index Table 2), 5% of Lignosulfonate (M)q) Uniformly mixing 1% of lauryl alcohol polyoxyethylene ether (JFC), 40% of diatomite and 44% of light calcium carbonate, and crushing to obtain the wettable powder.
Example 4 emulsifiable concentrate formulation
Heating and stirring 10% of compound (I) (index table 1 and index table 2), 5% of Nongru No. 500 (calcium salt), 5% of Nongru No. 602, 5% of N-methyl-2-pyrrolidone and 75% of xylene uniformly to obtain the missible oil.
Example 5 formulation of granules
Uniformly mixing 5% of compound (I) (index Table 1 and index Table 2), 1% of polyvinyl alcohol (PVA), 4% of sodium naphthalene sulfonate formaldehyde condensate (NMO) and 90% of clay, pulverizing, adding 20 parts of water to 100 parts of the mixture, kneading, extruding into granules of 14-32 meshes, and drying to obtain granules.
Example 6 Water dispersible granule formulation
20% of the compound (I) (index Table 1 and index Table 2), 4% of a naphthalenesulfonate formaldehyde condensate, 1% of a naphthalenesulfonate, 2% of white carbon black and 73% of kaolin were mixed and pulverized, and then kneaded with water, and then, the kneaded mixture was fed into a granulator equipped with a sieve having a predetermined specification to granulate. Then drying and screening (according to the range of a screen) to obtain a granular product.
Example 7 aqueous suspension formulation
The preparation method comprises the following steps of pre-mixing 20% of compound (I) (index table 1 and index table 2), 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 69.5% of deionized water uniformly, adding the mixture into a sand mill for sand milling, filtering to obtain a suspension mother solution, adding a prepared xanthan gum (0.1%) aqueous solution, shearing and mixing uniformly.
Third, Activity test
Examples of biological activity assays using the compounds of the present invention are given below, it being noted that the present invention is not limited solely to the scope of the following examples.
Example 8 indoor Activity measurement test
The inhibitory activity of the compounds on fungi was determined by the spore germination method. The test pathogens were plated on PDA plates for 3 days, and then 5 clumps of 0.5cm diameter were punched out at the edge of a fresh colony using a punch and inoculated with 30mL CMC (15g of carboxymethyl cellulose,1g of yeast extract,0.5g of MgSO4,1g of NH)4NO3,1g KH2PO4and 1L water) was cultured in a 50ml Erlenmeyer flask at 25 ℃ under illumination at 180rpm for 4 days to induce sporulation. The spores were filtered through three layers of paper wipes to prepare a spore suspension. Mixing conidia (final concentration of 10)4mL) was added to a 24-well (2.0 mL per well) petri dish containing a 2% sucrose solution, the test compound was dissolved in DMSO, and then the test compound was diluted with DMSO to the concentration tested, respectively. The test compounds were then added to 24-well dishes at different concentrations and tested for their activity on germination of conidia. After static culture for 3h at 25 ℃, counting the number of the germinated conidia in each hole by using a hemocytometer under a microscope,using the formula MGIR% ([ (C-N)/C)]X 100 calculating the spore germination inhibition ratio (MGIR), wherein C is the number of spores germinated in the untreated control group, and N is the number of spores germinated in the treated group. And calculating the germination rate of the conidia of each treatment. Each experiment was repeated three times. The pathogenic bacteria of the test are wheat scab original bacteria, cucumber gray mold pathogenic bacteria, rice sheath blight pathogenic bacteria and anthrax pathogenic bacteria.
In the invention, the in vitro bactericidal activity evaluation is carried out on the numbered compounds in the index table 1 and the index table 2, and the results show that the in vitro bactericidal activity evaluation takes the phenamacril as a control medicament: the compound of the invention has good bactericidal activity, particularly good bactericidal activity on head blight primordium, and the 'mg/L' refers to each mg of active matter/L, and the specific details are as follows:
at a concentration of 2.0mg/L, the inhibition rate of the compound 1, 12, 15, 24, 70, 93, 94, 96, 101, 102, 103, 104, 105, 116, 119, 128, 174, 197, 198, 200, 205, 206, 207, 208 on spore germination of the gibberellic disease protobacteria is more than 90%, and the inhibition rate of the control medicament, phenamacril (2.0mg/L), on spore germination of the gibberellic disease protobacteria is 76%;
at a concentration of 1.0mg/L, the inhibition rate of the compounds 1, 15, 24, 93, 94, 101, 102, 104, 105, 119, 197, 205, 206, 208 on spore germination of saprolegnia scabroscopicus was greater than 90%, and the inhibition rate of the control agent cyhalostrobin (1.0mg/L) on spore germination of saprolegnia scabroscopicus was 46%.
Example 9 field test of wheat scab
The field control effect test of wheat scab of the compound to be tested is carried out in Haian city of Jiangsu province, and the tested wheat variety is Jimai 22. The field trial used a random plot design, with three replicates per treatment. The area of each plot was 5 x 10 square meters. Fusarium graminearum conidium suspension (10) is sprayed on the wheat in the ear-sprouting poplar flowering period (15 percent)4/mL). After 2 days of inoculation, the test compound (5% emulsifiable concentrate) or the control drug phenamacril (25% suspending agent) is sprayed. 40 days after inoculation, the wheat scab Disease Index (DI) was counted for each plot. The disease index of wheat is evaluated according to 5 grades, the classification grade is numbered from 0 to 4, and the disease degree of one wheat strain is corresponding toThe percentage of (0 ═ 0; 1 ═ 1 to 25; 2 ═ 26 to 50; 3 ═ 51 to 75; 4 ═ 51 to 75)>75%). Using the formula [ (number of wheat per point X evaluation grade)/(total number of wheat X4)]X 100% the disease index for each treatment was calculated. The Abbott formula [ (negative control DI-treated DI)/negative control DI ] was used]The control effect of each treatment was calculated at 100% and the specific results are shown in table 4.
TABLE 4 field test results for wheat scab
Test agent
Dosage (g/ha)
The field control effect%
Compound 1
375
45.7±0.75
Compound 24
375
42.5±1.05
Compound 101
375
85.3±0.97
Compound 104
375
62.6±0.82
Cyanostrobin
375
60.3±1.28
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