Tetrahydrofuro pyridinedione and furanone heterocyclic compound

Abstract

The invention discloses a tetrahydrofuro-pyridinedione and furanone heterocyclic compound with insecticidal and bactericidal effects, preferably having a structure shown as a formula III and a formula IV, # imgabs0, a stereoisomer thereof and a pesticide acceptable salt, in the formula, R1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl and optionally substituted arylalkyl; r2 is selected from H, halogen, amido, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl and optionally substituted heteroaryl; r3 is selected from H, halogen, amido, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl and optionally substituted arylalkyl.

Description

Technical Field

[0001] The invention belongs to the field of pesticides, and in particular relates to tetrahydrofuranopyridinedione and furanone heterocyclic compounds with bactericidal and insecticidal effects. Technical Background

[0002] In recent years, some new varieties of pesticides with super high efficiency, low toxicity and low residue have been developed in the fields of insecticides, herbicides and fungicides. Their chemical structures are different from traditional organophosphorus, carbamate and pyrethroids, and are replaced by some novel heterocyclic and condensed heterocyclic structures. Among the patents of new pesticide products, about 90% are heterocyclic compounds, most of which are super high efficiency compounds. The dosage of some super high efficiency heterocyclic pesticides is only 10-100 g / hectare, or even as low as 5-10 g / hectare. These super high efficiency pesticides are not only low in cost, but more importantly, the impact on the environment is also reduced to a very small extent. Another feature of heterocyclic pesticides is that most heterocyclic compounds have very low toxicity to warm-blooded animals, and also low toxicity to birds and fish. Among heterocyclic compounds, nitrogen-containing heterocyclic compounds are particularly important and occupy a very important position in the newly developed pesticides. Among these nitrogen-containing heterocyclic compound pesticides, pyridine, pyrazole, pyrimidine, triazole, condensed heterocyclic compounds are the fastest growing fields this year, and fungicides, herbicides, and new ultra-high-efficiency insecticides have been continuously developed. Among nitrogen-containing heterocyclic compounds, pyridine derivatives are the most prominent, including not only insecticides and herbicides, but also high-efficiency fungicides, which has opened up new horizons for the development of chemical pesticides. Pyridine is a common and very important heterocycle in organic synthesis. Its application in pesticides can be traced back to the late 17th century and early 18th century in Europe, where people used tobacco extract as an insecticide. After analysis, it was confirmed that its active ingredient was nicotine, which is still used in many countries today. The real organic synthesis of pyridine pesticides began in the mid-1950s. The herbicide diquat developed by the British TCI Company in 1955 and the herbicide paraquat developed in 1958 still have a good market. Because of the unique effect of the pyridine ring in pesticide molecules, research on pyridine compounds has increased day by day. Currently, pyridines have almost spread to all fields and various structural types of pesticides. Summary of the invention

[0003] During the research process, the applicant first discovered that the tetrahydrofuranopyridinedione and furanone heterocyclic compounds of the present application have good bactericidal and insecticidal effects. The present invention provides a compound of formula III and formula IV having good bactericidal and insecticidal effects.

[0004] Specifically, the present invention provides a compound of formula III and its salts and stereoisomers, and the structure of the compound of formula III is as follows:

[0005] Its stereoisomers and pesticide-acceptable salts, wherein:

[0006] R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0007] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0008] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0009] Preferably, the compound of formula III is a compound of formula 3:

[0010]

[0011] The present invention also provides a compound of formula IV or a salt and stereoisomer thereof, and the structure of formula IV is as follows:

[0012]

[0013] Its stereoisomers and pesticide-acceptable salts, wherein:

[0014] R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0015] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0016] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0017] Preferably, the compound of formula IV is a compound of formula 4,

[0018]

[0019] The present invention also discloses a pesticide composition, which contains the compound of formula III or IV of the present invention, and their stereoisomers and pesticide-acceptable salts.

[0020] The invention also discloses the application of the compound of formula III and the compound of formula IV in preventing and controlling plant diseases and insect pests. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "including" will be understood to include the stated components or steps, without excluding other material components or steps.

[0022] In addition, in order to better illustrate the present invention, numerous specific details are given in the following detailed description.

[0023] Those skilled in the art will appreciate that the present invention can be implemented without certain specific details. In some embodiments, raw materials, methods, means, etc. that are well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present invention.

[0024] If the compounds of the formula I described herein are capable of forming geometrical isomers, such as E / Z isomers, both the pure isomers and mixtures thereof can be used in the compositions according to the invention.

[0025] If the compounds of the formula I described herein have one or more chiral centers and therefore exist as enantiomers or diastereomers, the pure enantiomers, racemates or diastereomers can be used in the compositions of the invention.

[0026] If the compounds of the formula I according to the invention have functional groups which can be ionized, they can also be used in the form of their agriculturally acceptable salts or mixtures thereof.

[0027] Suitable are generally salts of those cations whose cations do not have an adverse effect on the action of the active compounds ("agriculturally acceptable"). Preferred cations are ions of alkali metals, preferably lithium, sodium and potassium, ions of alkaline earth metals, preferably calcium and magnesium, and ions of transition metals, preferably manganese, copper, zinc and iron.

[0028] Anions useful for acid addition salts are primarily chloride, bromide, fluoride, iodide, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, nitrate, hydrogen carbonate, and carbonate.

[0029] The term halogen denotes in each case fluorine, chlorine, bromine and iodine.

[0030] All hydrocarbon chains, i.e., all alkyl groups, in the present invention may be straight or branched, and the subscripts Cn to Cm in all cases indicate the number of carbon atoms in the group. The term "alkyl" as used herein (and in other groups containing alkyl groups, such as the alkyl structural part of an alkoxy group) includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl.

[0031] In the present invention, "aryl" refers to a monovalent monocyclic or bicyclic aromatic hydrocarbon group of 6 to 10 ring atoms, such as phenyl or naphthyl, especially naphthyl, but not limited thereto. The aryl group may be substituted by an alkyl, halogen, cyano, nitro, cycloalkyl, heterocyclic, acylamino, ester group, etc., but not limited thereto.

[0032] The term "heteroaryl" of the present invention refers to an aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen and sulfur and preferably up to three heteroatoms as ring members. The heteroaryl ring does not contain adjacent oxygen atoms, adjacent sulfur atoms or adjacent oxygen and sulfur atoms within the ring. Preferred examples include pyrrolidine, piperidine, piperazine, morpholine, pyridine, pyrimidine, pyrazine, pyridazine, pyrroles, pyrazoles, imidazoles, triazoles, isoxazoles, oxazoles, isothiazoles, thiazoles, tetrazole, furans and thienyl, and further preferred pyrrolidine, piperidine, piperazine, morpholine, thiophene, pyrroles and imidazoles.

[0033] The term "arylalkyl" herein refers to a residue in which the aryl moiety is attached to the parent structure via an alkyl residue. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl, and the like. "Heteroaralkyl" refers to a residue in which the heteroaryl moiety is attached to the parent structure via an alkyl residue. Examples include furanylmethyl, pyridylmethyl, pyrimidinylethyl, and the like.

[0034] The term "optionally substituted" means that the relevant group may be substituted by a substituent or may not be substituted. Preferably, there are 1 to 5 optional substituents, more preferably 1 to 3 optional substituents, and even more preferably 1 or 2 optional substituents. In the case where a group is said to be optionally substituted, and in the case where the optional substitution of the group has more than one substituent, the more than one substituent may be the same or different.

[0035] When the relevant group (such as alkyl) is substituted with a substituent, the substituent may include hydroxyl, cyano, nitro, halogen, alkyl, alkoxy, and alkyl substituted with halogen to form a haloalkyl.

[0036] The statements made below with regard to the variables of the compounds of the formula (I) and preferred embodiments of the variables, features of the uses and methods according to the invention and features of the compositions according to the invention are valid both on their own and preferably in combination with one another.

[0037] The present invention first provides a compound of formula III,

[0038]

[0039] Its stereoisomers and pesticide-acceptable salts, wherein R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0040] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0041] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0042] In the preferred embodiment, R 1 Selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl.

[0043] In a more selective solution, R 1Selected from H, Ph, 2-FC6H4, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,5-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC 6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-CF3C6H4, 4-CF3C6H4, 3-thienyl, 2-naphthyl, 1-naphthyl, 4-FC6H4CH2CH2, Bn.

[0044] In the preferred technical solution, R 2 Selected from H, halogen, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted pyridyl.

[0045] In the more selective technical solution, R 2 Selected from H, halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, naphthyl, thienyl, pyridyl.

[0046] In the preferred technical solution, R 3 is selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl

[0047] In a more preferred technical solution, R 3 Selected from H, Ph, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3,5-(CF3)2C6H3, 4-PhC6H4, 2-thienyl, 2-naphthyl, 1-naphthyl, Me, Et, nPr, Bn.

[0048] Preferably, the compound of formula III is of formula 3:

[0049]

[0050] , where R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0051] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0052] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0053] In the preferred embodiment, R 1 Selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl.

[0054] In a more selective solution, R 1 Selected from H, Ph, 2-FC6H4, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,5-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC 6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-CF3C6H4, 4-CF3C6H4, 3-thienyl, 2-naphthyl, 1-naphthyl, 4-FC6H4CH2CH2, Bn.

[0055] In the preferred technical solution, R 2 Selected from H, halogen, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted pyridyl.

[0056] In the more selective technical solution, R 2 Selected from H, halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, naphthyl, thienyl, pyridyl.

[0057] In the preferred technical solution, R 3 is selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl

[0058] In a more preferred technical solution, R 3 Selected from H, Ph, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3,5-(CF3)2C6H3, 4-PhC6H4, 2-thienyl, 2-naphthyl, 1-naphthyl, Me, Et, nPr, Bn.

[0059] The present invention also provides a compound of formula IV,

[0060]

[0061] Its stereoisomers and pesticide-acceptable salts, wherein:

[0062] R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0063] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0064] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0065] R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0066] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0067] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0068] In the preferred embodiment, R 1 Selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl.

[0069] In a more selective solution, R 1 Selected from H, Ph, 2-FC6H4, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,5-2ClC6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4- MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-CF3C6H4, 4-CF3C6H4, 3-thienyl, 2-naphthyl, 1-naphthyl, 4-FPhEt, Bn.

[0070] In the preferred technical solution, R 2 Selected from H, halogen, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted pyridyl.

[0071] In the more selective technical solution, R 2 Selected from H, halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, naphthyl, thienyl, pyridyl.

[0072] In the preferred technical solution, R 3 is selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl

[0073] In a more preferred technical solution, R 3 Selected from H, Ph, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3,5-(CF3)2C6H3, 4-PhC6H4, 2-thienyl, 2-naphthyl, 1-naphthyl, Me, Et, nPr, Bn.

[0074] Preferably, Formula IV is Formula 4:

[0075]

[0076] R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl;

[0077] R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl;

[0078] R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

[0079] In the preferred embodiment, R 1 Selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl.

[0080] In a more selective solution, R 1 Selected from H, Ph, 2-FC6H4, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,5-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4- MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-CF3C6H4, 4-CF3C6H4, 3-thienyl, 2-naphthyl, 1-naphthyl, 4-FPhEt, Bn.

[0081] In the preferred technical solution, R 2 Selected from H, halogen, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted pyridyl.

[0082] In the more selective technical solution, R 2 Selected from H, halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, naphthyl, thienyl, pyridyl.

[0083] In the preferred technical solution, R 3 is selected from H, optionally substituted C1-C6 alkyl, optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted aryl C1-C6 alkyl

[0084] In a more preferred technical solution, R 3 Selected from H, Ph, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3,5-(CF3)2C6H3, 4-PhC6H4, 2-thienyl, 2-naphthyl, 1-naphthyl, Me, Et, nPr, Bn.

[0085] The preparation of the compounds of formula III and formula IV of the present invention can be prepared by the following scheme:

[0086]

[0087] The compound of formula I reacts with the compound of formula II in an organic solvent to generate compounds of formula III and formula IV. The organic solvent may be a halogenated alkane, and the reaction temperature is 0-100°C, preferably room temperature (room temperature in the present invention refers to 25°C, and left and right refers to plus or minus 5).

[0088] Preferably, the compounds of formula 3 and formula 4 can be prepared by the following scheme:

[0089]

[0090] Compound 1 and compound 2 are reacted in a solvent in the presence of a chiral catalyst to prepare compounds of formula 3 and 4. The reaction temperature is room temperature and the reaction time is 8-36 hours.

[0091] Furthermore, Morita-Baylis-Hillman (MBH) carbonate 1 (0.13 mmol) and β,γ-unsaturated butenolide 2 (0.1 mmol) were accurately weighed in a dry Shrek tube under an argon atmosphere, 2 mL of chloroform was added to dissolve, and finally dimethylphenylphosphine (20 mol%) was added through a microsyringe. Stirring was performed at room temperature until the substrate was completely consumed (monitored by TLC), and then concentrated. The residue was purified by flash column chromatography (dichloromethane / ethyl acetate = 20:1) to obtain the corresponding products 3 and 4.

[0092] The intermediate compound 1 of the present invention can be prepared by the following scheme.

[0093]

[0094] To a solution of allyl alcohol (5 mmol, 1 equiv.) in methanol (2 M) was added aqueous NaOH (0.9 M, 1.26 equiv.) and the resulting mixture was stirred at rt until the alcohol was completely consumed. The reaction mixture was then acidified with aqueous hydrochloric acid (37%) and extracted with dichloromethane (x3). The combined organic phases were washed with saturated aqueous Na2CO3 and brine and dried over anhydrous Na2SO4. The crude hydrolyzate was obtained by removal of the solvent and could be used for the amidation without further purification. To a stirred mixture of the hydrolyzate in dichloromethane (0.5 M) were added 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.2 equiv.) and amine (1 equiv.). The reaction mixture was stirred at room temperature until completion. The mixture was then separated by silica gel column chromatography (eluted with hexane / ethyl acetate). The eluate was concentrated and the crude product could be used for the next step without further purification. (In some cases, this step requires further column purification or recrystallization). Amide, 4-dimethylaminopyridine (0.05 equiv.) and dichloromethane (0.3 M) were added at room temperature, and finally di-tert-butyl dicarbonate (Boc2O) was slowly added dropwise (1.1 equiv.). The mixture was stirred at room temperature until the amide was consumed. The mixture was washed with 1N aqueous hydrochloric acid solution and brine, and then concentrated. The residue was purified by silica gel flash chromatography (hexane / ethyl acetate) to give compound 1.

[0095] The intermediate compound 2 of the present invention can be prepared by the following scheme.

[0096]

[0097] Substituted formyl propionic acid (26 mmol) was stirred in acetic anhydride (5 mL) and acetic acid (3 mL) containing a catalytic amount of p-toluenesulfonic acid (30 mg) for 2 hours. After the substrate was completely consumed, the mixture was diluted with distilled water (7 mL) and stirred for 30 minutes. The product was collected by filtration to obtain an off-white crystalline solid, which was washed with H2O / acetic acid (V / V=1:1) and then washed with H2O. The crude product was crystallized from methanol to obtain the desired product 2.

[0098] The invention also discloses a pesticide composition containing the compound of the invention.

[0099] The invention also discloses the application of the compound in preventing and controlling plant diseases and insect pests.

[0100] Preferably, the plant diseases described in the present invention are cotton wilt pathogen, rapeseed sclerotinia pathogen, pepper phytophthora pathogen and tomato gray mold pathogen.

[0101] Preferably, the pest described in the present invention is Plutella xylostella.

[0102] Since the compounds of the present invention have excellent fungicidal effects, the compounds of formula I of the present invention are suitable for plant protection in agriculture, forestry and horticulture. The harmful organisms to which the compounds of the present invention have a protective effect include, for example, Plutella xylostella.

[0103] The compounds of formula I of the present invention can control plant diseases and insect pests by using an effective amount of active compounds for controlling plant diseases and insect pests.

[0104] The pesticide composition of the present invention usually contains 0.1 to 95 wt%, preferably 0.5 to 90 wt%, of the compound of formula (I).

[0105] The pesticide composition of the present invention can be prepared into a suitable dosage form, and the dosage form can be emulsifiable concentrate, wettable powder or microemulsion, etc., but is not limited thereto.

[0106] The formulations are prepared in a conventionally known manner, for example by mixing the active compound with a solvent and / or a carrier and, if necessary, adding suitable emulsifiers and dispersants or other customary adjuvants.

[0107] The present invention is used for controlling plant diseases and insect pests of the following crops. The crops include: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybean, peanut, buckwheat, beet, rape, sunflower, sugarcane, tobacco, eggplant, tomato, sweet pepper, pepper, potato, cucumber, pumpkin, zucchini, watermelon, melon, Japanese radish, white radish, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, chrysanthemum, artichoke, lettuce, shallot, onion, garlic or asparagus, carrot, parsley, celery, parsnip, spinach, Swiss chard, apple, pear, papaya, peach, plum, nectarine, plum, cherry, apricot, prune, Wenzhou mandarin orange, lemon, lime, grapefruit, chestnut, walnut, hazelnut, almond, pistachio, cashew or macadamia nut, grape, persimmon, olive, loquat, banana, coffee, date, coconut palm, oil palm, etc.

[0108] Preparation Example

[0109] The preparation and application of the active ingredient of formula (I) of the present invention are illustrated by the following examples, but are not limited to these examples. The raw materials in the preparation examples of the present invention can be purchased from the market or synthesized by referring to the methods disclosed in the prior art.

[0110] Example 1 Synthesis of Compound 1a

[0111]

[0112] To a solution of the alcohol (5 mmol, 1 equiv.) in methanol (2 M) was added an aqueous NaOH solution (0.9 M, 1.26 equiv.) and the resulting mixture was stirred at rt until the alcohol was completely consumed. The reaction mixture was then acidified with an aqueous hydrochloric acid solution (37%) and extracted with dichloromethane (x3). The combined organic phases were washed with saturated aqueous N2CO3 and brine and dried over anhydrous Na2SO4. The crude hydrolyzate was obtained by removal of the solvent and could be used for the amidation without further purification. To a stirred mixture of the hydrolyzate in dichloromethane (0.5 M) were added 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 1.2 equiv.) and an amine (1 equiv.). The reaction mixture was stirred at room temperature until completion. The mixture was then separated by silica gel column chromatography (eluted with hexane / ethyl acetate). The eluate was concentrated and the crude product could be used for the next step without further purification. (In some cases, this step requires further column purification or recrystallization). The amide, 4-dimethylaminopyridine (0.05 equiv.) and dichloromethane (0.3 M) were added at room temperature, and finally di-tert-butyl dicarbonate (Boc2O) was slowly added dropwise (1.1 equiv.). The mixture was stirred at room temperature until the amide was consumed. The mixture was washed with 1N aqueous hydrochloric acid solution and brine, and then concentrated. The residue was purified by silica gel flash chromatography (hexane / ethyl acetate) to give compound 1a.

[0113] Example 2 Synthesis of Compound 2a

[0114]

[0115] Substituted formylpropionic acid (26 mmol) was stirred in acetic anhydride (5 mL) and acetic acid (3 mL) containing a catalytic amount of p-toluenesulfonic acid (30 mg) for 2 hours. After the substrate was completely consumed, the mixture was diluted with distilled water (7 mL) and stirred for 30 minutes. The product was collected by filtration to obtain an off-white crystalline solid, which was washed with H2O / acetic acid (V / V=1:1) and then with H2O. The crude product was crystallized from methanol to obtain the desired product 2a.

[0116] Example 3 Synthesis of Compound 3aa

[0117]

[0118] Under argon atmosphere, accurately weigh Morita-Baylis-Hillman (MBH) carbonate 1 (0.13 mmol) and β,γ-unsaturated butenolide 2 (0.1 mmol) in a dry Shrek tube, add 2 mL of chloroform to dissolve, and finally add dimethylphenylphosphine (20 mol%) via a microsyringe. Stir at room temperature until the substrate is completely consumed (monitored by TLC), then concentrate. The residue is purified by flash column chromatography (dichloromethane / ethyl acetate = 20:1) to obtain the corresponding cyclized product (3aS, 7aR)-6-methylene-4,7-diphenyltetrahydrofuran [3,2-b] pyridine-2,5 (3H, 4H) -dione (3aa) as a white solid 30.6 mg, yield 96%, melting point 203-205 ° C.

[0119] 1 H NMR(500MHz, CDCl3)δ7.46–7.41(m,2H),7.38(td,J=7.8,5.8Hz,4H),7.34–7.30(m,1H),7.30–7.25(m,1H),7.23–7.19(m,2H),6.27(t, J=1.6Hz,1H),5.48–5.41(m,1H),4.72(dd,J=6.2,3.4Hz,1H),3.20(dt,J=15.3,2.0Hz,1H),3.13(d,J=15.3Hz,1H),2.60–2.49(m,2H). 13 C NMR(126MHz, CDCl3)δ172.0,162.8,139.4,138.5,128.7,128.1,127.8,127.0,126.6,125.6,123.2,84.0,64.8,40.2,35.0.HRMS(ESI)calcd for C 20 H 18 NO3 + [M+H] + Calculated value: 320.1287, measured value: 320.1288.

[0120] Example 4 Synthesis of Compound 4aa

[0121]

[0122] Under argon atmosphere, accurately weigh Morita–Baylis–Hillman (MBH) carbonate 1a (0.13 mmol) and β,γ-unsaturated butenolide 2a (0.1 mmol) in a dry Shrek tube, add 2 mL of chloroform to dissolve, and finally add dimethylphenylphosphine (20 mol%) through a microsyringe. Stir at room temperature for 15 min and then concentrate. The residue is purified by flash column chromatography (dichloromethane / ethyl acetate = 20:1) to obtain the corresponding cyclized product ((S)-2-((5-oxo-2-phenyl-2,5-dihydrofuran-2-yl)methyl)-N-phenylacrylamide (4aa) as a white solid 21.0 mg, yield 70%, melting point 105-107°C.

[0123] 1 H NMR (500MHz, CDCl3) δ7.65(d,J=5.4Hz,2H),7.48–7.37(m,4H),7.35–7.21(m,5H),7.07(td,J=7.4,1. 2Hz,1H),5.88(d,J=5.6Hz,1H),5.82(s,1H),5.60(s,1H),3.49–3.35(m,1H),2.96(d,J=14.0Hz,1H). 13 C NMR (126MHz, CDCl3) δ171.2,165.3,157.8,137.9,137.6,136.4,128.1,127.9,127.5,123.9,123.7,122.9,119.2,118.8,89.3,40.9.IR(film)ν max 1759,1680,1600,1521,1440,1275,1255,1026cm –1 ; HRMS (ESI) calculation for C 20 H 18 NO3 + [M+H] + Calculated value: 320.1287, measured value: 320.1288

[0124] The following compounds were prepared by methods similar to those described above.

[0125] Table 1 Heterocyclic compounds prepared by the present invention

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132]

[0133]

[0134]

[0135] Biological activity assay

[0136] (I) General method for determination of antibacterial activity

[0137] 1. Culture medium preparation

[0138] Preparation of culture medium: Peel the potatoes, cut them into small pieces, weigh 200g, wrap them with gauze, add them to 1000mL of boiling deionized water, boil them, simmer for 30min, and then add deionized water to 1000mL. Add 20g of agar powder, stir with a glass rod to dissolve it, add 20g of glucose, stir well, add deionized water to 1000mL, and finally dispense them into Erlenmeyer bottles and seal them with sterile sealing film. Put the Erlenmeyer bottles into the autoclave and adjust to 121℃ for 30min.

[0139] Preparation of drug-loaded culture medium (need to be performed on a sterile operating table): Dissolve the target compound in dimethyl sulfoxide to prepare a 30 mg / mL stock solution. After sterilization on a clean bench for 30 minutes, dilute the prepared stock solution with PDA culture medium to a 90 mg / L drug-loaded culture medium under sterile conditions on a clean bench, and pour into a culture dish, about 15 mL per dish, to obtain a drug-loaded culture plate.

[0140] 2. In vitro antibacterial activity assay

[0141] The mycelial growth rate method was used to determine the in vitro antibacterial activity and EC 50 . First sterilize the sterile operating table for 30 minutes, and sterilize the puncher and the cake picker with an alcohol lamp. After cooling, use the puncher to punch the activated pathogens into 5mm cakes. Use the cake picker to inoculate the punched cake in the middle of the drug-containing plate, with the hyphae contacting the culture medium. Place the inoculated plate in a constant temperature incubator at 25℃ and keep it dark.

[0142] 3. Results investigation and analysis:

[0143] The colony diameter was determined by the cross method and the antibacterial activity was calculated by the following formula.

[0144] Mycelium growth inhibition rate = (control colony growth diameter - treatment colony growth diameter) / (control colony growth diameter) × 100%

[0145] According to the inhibition rate of the set concentration gradient, the EC50 value was calculated using IBM SPSS statistics 25 software.

[0146] Table 2 Bactericidal activity of the compounds of the present invention against various pathogenic fungi

[0147]

[0148]

[0149] Table 3 Inhibition rate of the compounds of the present invention on pathogens

[0150]

[0151] Table 4 EC of the compounds of the present invention 50 value

[0152]

[0153] (II) Determination of insecticidal activity

[0154] 1. Insecticidal determination method:

[0155] Preparation of drug solution A certain amount of compound 3 was weighed on a balance (0.001 g), prepared into a 1% solution with DMSO, and then diluted to the test concentration with distilled water containing 0.1% Tween-80 for later use.

[0156] Activity assay for diamondback moth (Plutella xylostella): Dipping method. Take an appropriate amount of cabbage leaves and soak them in the drug for 15 seconds, then place them in a plastic petri dish to dry naturally in the shade. Inoculate each dish with 10 2nd-instar diamondback moth larvae and place them in an observation room at 22±2℃ and light intensity (16 / 8h). Observe 48h-72h after drug application, and touch the insect body with a brush. If there is no reaction, it is considered dead. Repeat 3 times.

[0157] Table 5 Insecticidal activity of target compounds against Plutella xylostella at different concentrations (μg / mL) (%)

[0158]

[0159]

[0160] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner and including the order of combination, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A compound selected from formula III and formula IV, Its stereoisomers, pesticide-acceptable salts, in, R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl; R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl; R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

2. The compound according to claim 1, characterized in that The compound is selected from Formula 3 and Formula 4, Where R 1 is selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl; R 2 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl; R 3 is selected from H, halogen, amine, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl.

3. The compound according to claim 1 or 2, characterized in that R 1 Selected from H, Ph, 2-FC6H4, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,5-Cl2C6H3, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-CF3C6H4, 4-CF3C6H4, 3-thienyl, 2-naphthyl, 1-naphthyl, 4-FC6H4CH2CH2, Bn.

4. The compound according to claim 1 or 2, characterized in that R 2 Selected from H, halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, naphthyl, thienyl, pyridyl.

5. The compound according to claim 1 or 2, characterized in that R 3 Selected from H, Ph, 3-FC6H4, 4-FC6H4, 3-ClC6H4, 4-ClC6H4, 3,4-Cl2C6H4, 3-BrC6H4, 4-BrC6H4, 2-MeC6H4, 3-MeC6H4, 4-MeC6H4, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3,5-(CF3)2C6H4, 4-PhC6H4, 2-thienyl, 2-naphthyl, 1-naphthyl, Me, Et, nPr, Bn.

6. A compound selected from the group consisting of the compounds listed in the following table:

7. A pesticide composition, characterized in that: Containing the compound according to any one of claims 1 to 6.

8. A method for preparing compounds of formula III and formula IV, characterized in that: The synthetic route is as follows:

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