Patent Grant
8222280
The present invention relates to insecticide, fungicide. Specifically to ether compounds with nitrogen-containing 5-member heterocycle and the uses as insecticide or fungicide in agriculture or other fields thereof.
It is well known that insects in general can cause significant damage, not only to crop growth in agriculture, but also, for example, to constructions and turf where the damage is caused by soil-borne insects (such as termites and white grubs).
Such damage may result in the loss of millions of dollars concerning crop, turf or constructions. Insecticides and acaricides are useful for controlling insects and acarids, but may cause significant damage to crops such as wheat, corn, soybeans, potatoes and cotton. For crop protection, insecticides and acaricides are desired which can control the insects and acarids while without damaging the crops, and have no deleterious effects to mammals and other living organisms.
The following patents disclosed a variety of dihalopropene compounds with insecticidal and acaricidal activities: CN1137265, CN1318535, CN1681771, CN1780818, CN1780825, CN1860874, CN101208088, U.S. Pat. No. 5,872,137, U.S. Pat. No. 5,922,880, U.S. Pat. No. 6,071,861, US20060247283, US20050288186, US20040224994, US20070142229 and WO2003074498 etc. However, there is no report whether the dihalopropene compounds have fungicidal activity. Meanwhile people will still need to continue developing novel insecticide and fungicide in order to prevent diseases and insect pests in agricultural or other fields. The representative compound Pyridalyl is a patent product of Japan sumitomo chemical Co., Ltd, and has good insecticidal activity against lepidoptera of vegetables and cotton. The structure is as follows:
The object of the present invention is to provide ether compounds with nitrogen-containing 5-member heterocycle with biological activity against all sorts of crops diseases and insects at very low doses, the another of the present invention is to provide compounds which can be applied in agriculture to control diseases and insects in plant or used as insecticides and fungicides in other fields.
Detailed description of the invention is as follows:
The present invention provides ether compounds with nitrogen-containing 5-member heterocycle having general formula I:
wherein:
R1 is selected from H, CO2R6, C1-C12alkyl, C1-C12haloalkyl, C1-C12alkoxyC1-C12alkyl, C1-C12haloalkoxyC1-C12alkyl, C3-C6cycloalkyl or R7;
R2 is selected from H, halo, CN, CO2R6, C1-C12alkyl, C1-C12haloalkyl, C1-C12alkoxy, C1-C12haloalkoxy, C1-C12alkylthio, C1-C12haloalkylthio, C3-C6cycloalkyl or R7;
R3, R4 and R5 mutually independently may be the same or different, selected from H, halo, OH, SH, CN, NO2, C1-C12alkyl, C1-C12haloalkyl, C1-C12alkylcarbonyl, C2-C12alkenyl, C2-C12haloalkenyl, C2-C12alkynyl, C1-C12alkoxy, C1-C12haloalkoxy, C2-C12alkenyloxy, C2-C12haloalkenyloxy, C3-C12alkynyloxy, C3-C12haloalkynyloxy, C1-C12alkylthio, C1-C12haloalkylthio, C1-C12alkylsulfonyl, C1-C12alkylsulfinyl, C1-C12alkoxyC1-C12alkyl, C1-C12alkoxycarbonyl, C1-C12alkoxycarbonylC1-C12alkyl, or C1-C12haloalkoxyC1-C12alkyl;
X is selected from NR8 or O;
R8 is selected from H, C1-C12alkyl, C1-C12haloalkyl, C1-C12alkoxyC1-C12alkyl, C1-C12haloalkoxyC1-C12alkyl, C3-C6cycloalkyl or R7;
Y1 and Y2 mutually independently may be the same or different, selected from H, F, Cl, Br, CH3, CN or CF3;
A1 and A2 mutually independently may be the same or different, selected from O, S or NR6;
R6 is selected from H or C1-C12alkyl;
R7 is selected from aryl, heteroaryl, arylC1-C12alkyl or heteroarylC1-C12alkyl, or above group substituted with 1-5 substitutents selected from halo, NO2, CN, CO2R6, CONHR6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkylsulfonyl or R7;
Q is selected from —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2—, —CH(CH3)—, —CH(CH3)CH2—, —CH(CH3)CH2CH2—, —CH2CH2CH(CH3)—, —CH(C2H5)—, —C(CH3)2—, —CH(CH3)CH(CH3)—, —CH2C(CH3)2CH2—, —CH2CH2OCH2CH2—, —CH2CH2NHCH2CH2—, —CH2CH2SCH2CH2—, —CH2CH2SO2CH2CH2—, —CH2COCH2—, —COCH2CO—, —CH2CH2CO—, —COCH2CH2—, —CH2CO—, —COCH2—, —CH2C(═NOCH3)CH2—, —CH2C(═NN(CH3)2)CH2—, —CH2CH(OH)CH2—, —CH2CH(OCH3)CH2—, —CH2CH(OCOCH3)CH2— or
A2 links with heterocycle at the 3, 4 or 5-position; when A2 links with heterocycle at the 5-position, R1 is at 3-position, R2 is at 4-position; when A2 links with heterocycle at the 3-position, R1 is at 5-position, R2 is at 4-position; when A2 links with heterocycle at the 4-position, R1 is at 3-position, R2 is at 5-position.
The preferred compounds of general formula (I) of this invention are:
R1 is selected from H, CO2R6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6haloalkoxyC1-C6alkyl, C3-C6cycloalkyl or R7;
R2 is selected from H, halo, CN, CO2R6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6cycloalkyl or R7;
R3, R4 and R5 mutually independently may be the same or different, selected from H, halo, or C1-C6alkyl;
X is selected from NR8 or O;
R8 is selected from H, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6haloalkoxyC1-C6alkyl, C3-C6cycloalkyl or R7;
Y1 and Y2 mutually independently may be the same or different, selected from H, F, Cl, Br, CH3, CN or CF3;
A1 and A2 mutually independently may be the same or different, selected from O, S or NR6;
R6 is selected from H or C1-C6alkyl;
R7 is selected from phenyl, pyridinyl, pyrimidinyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, furanyl, thiophen, thiazolyl, benzyl, pyridylmethyl, thiophenylmethyl or thiazolylmethyl, or above group substituted with 1-3 substitutents selected from halo, NO2, CN, CO2R6, CONHR6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkylsulfonyl, phenyl, 4-chloro-phenyl, phenoxy or 4-chloro-phenoxy;
Q is selected from —CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2COCH2— or
A2 links with heterocycle at the 3, 4 or 5-position; when A2 links with heterocycle at the 5-position, R1 is at 3-position, R2 is at 4-position; when A2 links with heterocycle at the 3-position, R1 is at 5-position, R2 is at 4-position; when A2 links with heterocycle at the 4-position, R1 is at 3-position, R2 is at 5-position.
Further more, the preferred compounds of general formula (I) of this invention are:
R1 is selected from H, CO2R6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6haloalkoxyC1-C6alkyl, C3-C6cycloalkyl or R7;
R2 is selected from H, halo, CN, CO2R6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6cycloalkyl or R7;
R3 is Cl;
R4 and R5 mutually independently may be the same or different, selected from H or Cl;
X is selected from NR8 or O;
R8 is selected from C1-C6alkyl, C1-C6haloalkyl or R7;
Y1 and Y2 are Cl;
A1 and A2 are O;
R6 is selected from H or C1-C6alkyl;
R7 is selected from phenyl, pyridinyl, furanyl, thiophen, thiazolyl or benzyl, or above group substituted with 1-3 substitutents selected from halo, NO2, CN, CO2R6, CONHR6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkylsulfonyl, phenyl, 4-chloro-phenyl, phenoxy or 4-chloro-phenoxy;
Q is selected from —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
A2 links with heterocycle at the 3, 4 or 5-position; when A2 links with heterocycle at the 5-position, R1 is at 3-position, R2 is at 4-position, the structure is represented by general formula I-1; when A2 links with heterocycle at the 3-position, R1 is at 5-position,
R2 is at 4-position, the structure is represented by general formula I-2; when A2 links with heterocycle at the 4-position, R1 is at 3-position, R2 is at 5-position, the structure is represented by general formula I-3;
Even more preferred compounds of formula (I-1) or formula (I-2) of this invention are:
R1 is selected from H, CO2R6, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyC1-C6alkyl, C1-C6haloalkoxyC1-C6alkyl, C3-C6cycloalkyl or R7;
R2 is selected from H, F, Cl, Br, CN, CO2R6 or C1-C6alkyl;
R4 and R5 mutually independently may be the same or different, selected from H or Cl;
X is NR8;
R8 is C1-C4alkyl;
R6 is selected from H or C1-C4alkyl;
R7 is selected from phenyl, or phenyl substituted with 1-3 substitutents selected from F, Cl, Br, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy or C1-C6alkylthio;
Q is selected from —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—; Or, the compounds of formula (I-3) are:
R1 is selected from H, CO2R6 or C1-C6alkyl;
R2 is selected from H, F, Cl, Br or C1-C6alkyl;
R4 and R5 mutually independently may be the same or different, selected from H or Cl;
X is NR8;
R8 is selected from C1-C4alkyl or R7;
R6 is selected from H or C1-C4alkyl;
R7 is selected from phenyl, or phenyl substituted with 1-3 substitutents selected from F, Cl, Br, CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy or C1-C6alkylthio;
Q is selected from —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—.
Most preferred compounds of formula (I-1) or formula (I-2) of this invention are:
R1 is selected from phenyl, or phenyl substituted with 1-3 substituents selected from F, Cl, Br, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy or C1-C4alkylthio;
R2 is selected from H, C1 or C1-C4alkyl;
R4 and R5 mutually independently may be the same or different, selected from H or Cl;
X is NR8;
R8 is C1-C4alkyl;
R6 is selected from H or C1-C4alkyl;
Q is selected from —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—; Or, the compounds of formula (I-3) are:
R1 is selected from H, CO2R6 or C1-C4alkyl;
R2 is selected from H, F, Cl, Br or C1-C4alkyl;
R4 and R5 mutually independently may be the same or different, selected from H or Cl;
X is NR8;
R8 is selected from C1-C4alkyl, phenyl, or phenyl substituted with 1-3 substituents selected from F, Cl, Br, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy;
R6 is selected from H or C1-C4alkyl;
Q is selected from —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—.
It must be noted that, as used in this specification, the appended claims and the general formula (I),
The “unsubstituent(s)” denote(s) all the substitute group(s) is (are) H.
The “halo” denotes fluorine, chlorine, bromine or iodine.
The “alkyl” stands for straight-chain or branched alkyl, such as methyl, ethyl, propyl, isopropyl or tert-butyl.
The “haloalkyl” stands for straight or branched chain alkyl, in which hydrogen atom can be all or partly substituted with halogen, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl.
The “alkenyl” stands for a straight-chain or branched, having double bonds at any position such as vinyl or allyl.
The “alkynyl” stands for a straight-chain or branched, having triple bonds at any position such as ethynyl, propynyl.
The aryl and aryl in arylalkyl include phenyl or naphthyl etc.
The “heteroaryl” in this invention stands for five member ring or six member ring containing one or more N, O, S hetero atoms. Such as pyridinyl, furanyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, thiazolyl, benzothiazolyl or benzofuranyl.
The preferred groups and substituents of R1 and R2 in preferred general formula (I-1), (I-2), (I-3) of this invention refer to Tables 1-9.
R4 and R5 mutually independently may be the same or different, selected from H or Cl.
In the general formula (I-1): When R1 is phenyl, the substituted groups of phenyl refer to Table 1. When R1 is pyridinyl, the substituted groups of pyridinyl refer to Tables 2-4. When R1 is thiazolyl, the substituted groups of thiazolyl refer to Table 5. When R1 is thiophene or furanyl, the substituted groups of furan refer to Tables 6-7. When R1 is other groups, the substituted groups refer to Table 8.
In the general formula (I-1): When R2 is phenyl, the substituted groups of phenyl refer to Table 1. When R2 is pyridinyl, the substituted groups of pyridinyl refer to Tables 2-4. When R2 is thiazolyl, the substituted groups of thiazolyl refer to Table 5. When R2 is thiophene or furanyl, the substituted groups of furan refer to Tables 6-7. When R2 is other groups, the substituted groups refer to Table 9.
R1, R2 in general formula (I-2), (I-3) are defined as that in general formula (I-1).
—R4 and R5 mutually independently may be the same or different, selected from H or Cl.
R4 and R5 mutually independently may be the same or different, selected from H or Cl.
The present invention is also explained by the following compounds in Tables 10-12, but without being restricted thereby.
The compounds represented by the general formula (I) were prepared by condensation reaction of intermediate pyrazole or isoxazole compounds containing hydroxy group represented by the general formula (II) with haloallyl intermediates represented by the general formula (IV) under basic conditions, or by condensation reaction of intermediate pyrazole or isoxazole compounds represented by the general formula (III) with haloallyl intermediates containing hydroxy group represented by the general formula (V) under basic conditions according to the following schemes:
The compounds of the general formula (III) and (IV), wherein L is leaving group, selected from Cl or Br, other groups are as defined above.
The compounds of the general formula (IV) and (V) can be prepared according to the known methods, which disclosed in the patents including CN1860874, US20030073847 and WO9727173, etc.
The reaction was carried out in proper solvent and the proper solvent mentioned may be selected from tetrahydrofuran, acetonitrile, toluene, xylene, benzene, DMF, DMSO, acetone or butanone and so on.
The proper base mentioned may be selected from potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide and so on.
The proper temperature mentioned is from room temperature to boiling point of the solvent, normal temperature is from 20 to 100° C.
The reaction time is in the range of 30 minutes to 20 hours, generally being 1-10 hours.
Intermediate represented by the general formula (II) can be purchased or prepared according to the known methods. Wherein, when hydroxy group is at 3- or 5-position of 5-member heterocycle, intermediate represented by the general formula (II) can be prepared by reaction of intermediate represented by the general formula (VI) with (substituted)hydrazine or hydroxylamine, according to the methods disclosed in WO2005080344A1, Synlett 2004, 5, 795-798, J. Chem. Soc., Perkin Trans. 2, 1987, 969-975 and so on. When hydroxy group is at 4-position of 5-membered heterocycle, intermediate represented by the general formula (II) can be prepared by cyclization from amines and the intermediate obtained by esterification of intermediate represented by the general formula (VI), referring to Organic Preparation and Procedures International, 2002, 34(1): 98-102. Intermediate represented by the general formula (III) can be prepared by halogenation of intermediate represented by the general formula (II).
The compounds having general formula (I) have a high insecticidal activity against adults, larvae and eggs of insects which are harmful in the agricultural, civil and zoo-technical fields, the compounds also exhibit preferable fungicidal activity. A further object of the present invention therefore relates to the use of the compounds having general formula (I) as insecticides and/or fungicides, both in agriculture and other fields.
In particular, the compounds having general formula (I) are active against important species of lepidopteran such as striped rice borer (Chilo suppressalis), rice leaf roller (Cnaphalocrocis medinalis), corn borer (Pyrausta nubilalis), tobacco budworm (Heliothis virescens), fruit moth, diamond back moth (Plutella xylostella), beet armyworm (Laphygma exigua), cotton leafworm (Spodoptera litura) and so on, especially showed very good control of diamond back moth and beet armyworm at very low doses. The compounds in present invention also have high activity against homoptera such as aphids etc. Therefore the compounds of general formula (I) in the invention prefer to be used to control the pests of lepidoptera and homoptera in agriculture and other fields. Additionally, some compounds in present invention also exhibit good fungicidal activity, which can be used to control rice blast, tomato late blight, vegetable grey mould, wheat powdery mildew, cucumber downy mildew, anthracnose, etc, especially showed very good control of rice blast, cucumber downy mildew and anthracnose.
Meanwhile, the compounds having general formula (I) have a low toxicity to many useful insects and mites, mammals, fishes and birds, furthermore, the compounds have no phytotoxicity.
Thanks to their positive characteristics, the compounds in the invention can be advantageously used in protecting crops of farming and gardening, domestic and breeding animals, as well as environments frequented by human beings, from harmful insects and fungi.
In order to obtain the desired effect, the dosage of compound to be applied can vary with various factors, for example, the used compound, the protected crop, the type of harmful organism, the degree of infestation, the climatic conditions, the application method and the adopted formulation.
Doses of compound in the range of 10 g to 1000 g per hectare generally can provide a sufficient control to the harmful insects and fungi.
An another object of the present invention also relates to a method for controlling insects and/or phytopathogenic fungi in crops of farming and gardening and/or on domestic and breeding animals and/or environments frequented by human beings, by the application of the compounds having general formula (I). In particular, the dosage of compound to be applied varies from 10 g to 1000 g per hectare.
For practical use in agriculture, it is usually useful to use compositions containing one or more compounds having general formula (I).
Therefore a further object of the present invention relates to insecticidal and/or fungicidal compositions containing one or more compounds having general formula (I) as active ingredient, and the weight percentage of the active ingredient in the composition is 0.1-99%.
Compositions can be used in the form of dry powders, wettable powders, emulsifiable concentrates, microemulsions, pastes, granulates, solutions, suspensions, etc.: the selection of the type of composition depends on the specific use.
The compositions are prepared in the known way, for example by diluting or dissolving the active substance with a solvent medium and/or a solid diluent, optionally in the presence of surface-active agents.
Solid diluents or carriers which can be used include, for example: silica, kaolin, bentonite, talc, diatomite, dolomite, calcium carbonate, magnesia, chalk, clays, synthetic silicates, attapulgite, seppiolite and so on.
Liquid diluents which can be used include, for example, in addition to water, aromatic organic solvents (xylols or mixtures of alkylbenzols, chlorobenzene, etc.), paraffins (petroleum fractions), alcohols (methanol, propanol, butanol, octanol, glycerin), esters (ethyl acetate, isobutyl acetate, etc.), ketones (cyclohexanone, acetone, acetophenone, isophorone, ethylamylketone, etc.), amides (N,N-dimethylformamide, N-methylpyrrolidone, etc.).
Surface-active agents which can be used include salts of sodium, calcium, triethylamine or triethanolamine of alkylsulfonates, alkylarylsulfonates, polyethoxylated alkylphenols, polyethoxylated esters of sorbitol, ligninsulfonates, etc.
The compositions can also contain special additives for particular purposes, for example adhesion agents such Arabic gum, polyvinyl alcohol, polyvinyl-pyrrolidone, etc.
The concentration of active ingredient in the above compositions can vary within a wide range depending on the active compound, the applications for which they are destined, the environmental conditions and the type of adopted formulation. In general the concentration of active ingredient ranges from 0.5 to 90%, preferably from 5 to 60%.
If required, other active ingredients being compatible with the compounds having general formula (I) can be added to the compositions, such as, other acaricides/insecticides, fungicides, plant growth regulators, antibiotics, herbicides, fertilizers.
The preparation methods of several common formulations examples in the present invention are as follows:
The preparation of suspension concentrate: in commonly used for producing the suspension concentrate, the active component in formula is 5%-35%. With water as the medium, the compound in the invention, dispersing agent, suspending agent and antifreeze are added to sanding machine for grinding to make suspension concentrate.
The preparation of water emulsion: the compound in the invention, solvent and emulsifier are mixed together, to make a homogeneous oil phase. The water is mixed with antifreeze to make a homogeneous water phase. In the high-speed stirring, the aqueous phase is added to the oil phase or oil phase is added to the aqueous phase, forming the water emulsion with good dispersity. The active component of water emulsions is generally 5%-15% in this invention. For the production of concentrated emulsions, the compounds of this invention are dissolved in one or more of the mixed solvent, and then emulsifier was added to enhance dispersion effects in the water.
The preparation of wettable powder: according to formulation requirements, the compound in the invention, surfactants and solid diluents are mixed well, after smashing through ultrafine pulverizer, that is the wettable powder products (for example, 10%-60%). For the preparation of the spraying wettable powder, the compounds of this invention can be formed the mixture with solid powder, such as clay, inorganic silicates, carbonates, as well as wetting agents, adhesives and/or dispersant agent.
The preparation of water dispersible granules: the compound in the invention and powdered solid diluents, wetting agents and adhesives are mixed to smash, kneading together with water, added to the granulation certain mesh machine for granulation, then by drying and sieving (at the scope screen). Also, the compound, in the invention dispersants, disintegrants, wetting agents and solid diluent are added to sanding machine, grinding in water to produce suspension and then spray-drying granulation, usually the content of the prepared granular products is 20%-30%.
The following examples are illustrative of the present invention, but without being restricted thereby.
Sulfonyl chloride (0.95-3 equiv) in toluene was added dropwise to a solution of 4-(3,3-dichloroallyloxy)phenol (4.10 g, 18.5 mmol) and di-n-butylamine 4 drop (0.1 mL) in toluene (30 mL) at 65-70° C. for 2 h and the reaction mixture stirred at room temperature for further 1-2 h and monitored by TLC. After the reaction was over, the mixture was diluted with saturated sodium hydrogen carbonate solution, toluene layer was separated and water layer was extracted with toluene. The organic layer was combined, dried and evaporated. The residue was purified via silica gel column chromatography to obtain intermediate.
2,6-Dichloro-4-(3′,3′-dichloroallyloxy)phenol (3.8 g) in 10 mL DMF was added dropwise to a solution of 1,3-dibromopropane (4.2 g) and anhydrous potassium carbonate (2.9 g) in 20 mL DMF at 15° C. for 1 h and the reaction was monitored by TLC. After the reaction was over, the mixture was diluted with 50 mL brine and extracted with ethyl acetate (60 mL) three times. The combined extracts were dried, evaporated and the residue was purified via silica gel column chromatography to obtain intermediate IV-1 (4.35 g).
Intermediate II-1 (0.22 g, prepared according to the method disclosed in WO 2005080344A1) and anhydrous potassium carbonate (0.23 g) were added to a 100 mL flask, then 40 mL DMF and intermediate IV-1 (0.45 g) were added to the solution. The reaction mixture was heated to 35° C. for 3 h and monitored by TLC. After the reaction was over, the mixture was evaporated under reduced pressure, diluted with 50 mL brine and extracted with ethyl acetate (60 mL) for three times. The combined extracts were dried and evaporated and the crude product was purified via silica gel column chromatography to obtain compound 2 (0.37 g).
Intermediate II-2 (0.18 g, prepared according to the method disclosed by J. Chem. Soc., Perkin Trans. 2, 1987, 969-975) and anhydrous potassium carbonate (0.20 g) were added to a 100 mL flask, then 40 mL DMF and intermediate IV-1 (0.40 g) were added to the solution. The reaction mixture was heated to 35° C. for 3 h and monitored by TLC. After the reaction was over, the mixture was evaporated under reduced pressure, diluted with 50 mL brine and extracted with ethyl acetate (60 mL) for three times. The combined extracts were dried and evaporated and the crude product was purified via silica gel column chromatography to obtain compound 269 (0.33 g).
Intermediate II-3 (0.24 g, prepared according to the method disclosed by J. Chem. Soc., Perkin Trans. 2, 1987, 969-975) and anhydrous potassium carbonate (0.27 g) were added to a 100 mL flask, then 40 mL DMF and intermediate IV-1 (0.49 g) were added to the solution. The reaction mixture was heated to 35° C. for 3 h and monitored by TLC. After the reaction was over, the mixture was evaporated under reduced pressure, diluted with 50 mL brine and extracted with ethyl acetate (60 mL) for three times. The combined extracts were dried and evaporated and the crude product was purified via silica gel column chromatography to obtain compound 367 (0.30 g).
Intermediate II-4 (0.25 g, prepared according to the method disclosed in Organic Preparation and Procedures International, 2002, 34(1): 98-102) and anhydrous potassium carbonate (0.28 g) were added to a 100 mL flask, then 40 mL DMF and intermediate IV-1 (0.52 g) were added to the solution. The reaction mixture was heated to 35° C. for 3 h and monitored by TLC. After the reaction was over, the mixture was evaporated under reduced pressure, diluted with 50 mL brine and extracted with ethyl acetate (60 mL) for three times. The combined extracts were dried and evaporated and the crude product was purified via silica gel column chromatography to obtain compound 546 (0.35 g).
Other compounds of the general formula (I) were prepared according to the above examples.
Melting point and 1HNMR spectrum (1HNMR, 300 MHz, internal standard: TMS, solvent CDCl3) of some compounds of this invention are as follows:
Compound 1: oil. δppm 7.75 (m, 2H), 7.38 (m, 2H), 7.28 (m, 1H), 6.85 (s, 2H), 6.11 (t, 1H), 5.89 (s, 1H), 4.58 (d, 2H), 4.42 (t, 2H), 4.15 (t, 2H), 3.71 (s, 3H), 2.32 (m, 2H).
Compound 2: m.p. 68-70° C. δppm 7.68 (m, 2H), 7.33 (m, 2H), 6.85 (s, 2H), 6.11 (t, 1H), 5.85 (s, 1H), 4.58 (d, 2H), 4.41 (t, 2H), 4.15 (t, 2H), 3.70 (s, 3H), 2.32 (m, 2H).
Compound 8: oil. δppm 7.67 (m, 2H), 7.27 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 5.84 (s, 1H), 4.59 (d, 2H), 4.40 (t, 2H), 4.14 (t, 2H), 3.69 (s, 3H), 2.50 (s, 3H), 2.32 (m, 2H).
Compound 13: m.p. 78-80° C. δppm 7.67 (m, 2H), 6.91 (m, 4H), 6.11 (t, 1H), 5.81 (s, 1H), 4.58 (d, 2H), 4.40 (t, 2H), 4.15 (t, 2H), 3.83 (s, 3H), 3.69 (s, 3H), 2.32 (m, 2H).
Compound 16: oil. δppm 7.64 (m, 2H), 7.50 (m, 2H), 6.85 (s, 2H), 6.11 (t, 1H), 5.86 (s, 1H), 4.58 (d, 2H), 4.41 (t, 2H), 4.14 (t, 2H), 3.70 (s, 3H), 2.32 (m, 2H).
Compound 21: oil. δppm 7.78 (m, 1H), 7.42 (m, 1H), 7.23 (m, 2H), 6.84 (s, 2H), 6.11 (m, 2H), 4.58 (d, 2H), 4.42 (t, 2H), 4.16 (t, 2H), 3.72 (s, 3H), 2.33 (m, 2H).
Compound 76: oil. δppm 7.63 (d, 2H), 7.41 (t, 2H), 7.32 (t, 1H), 6.83 (s, 2H), 6.10 (t, 1H), 4.58 (d, 2H), 4.40 (t, 2H), 4.18 (t, 2H), 3.76 (s, 3H), 2.31 (m, 2H), 2.17 (s, 3H).
Compound 130: oil. δppm 7.70 (m, 2H), 7.34 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.42 (t, 2H), 4.15 (t, 2H), 4.04 (m, 2H), 2.32 (m, 2H), 1.37 (m, 3H).
Compound 148: oil. δppm 7.68 (d, 2H), 7.33 (d, 2H), 7.08 (s, 1H), 6.39 (t, 1H), 6.10 (s, 1H), 4.77 (d, 2H), 4.39 (t, 2H), 4.24 (t, 2H), 3.64 (s, 3H), 2.34 (m, 2H).
Compound 166: oil. δppm 7.55 (m, 2H), 7.35 (m, 2H), 7.25 (m, 1H), 7.02 (s, 1H), 6.35 (t, 1H), 4.76 (d, 2H), 4.35 (t, 2H), 4.18 (t, 2H), 3.69 (s, 3H), 2.30 (m, 2H), 2.14 (s, 3H).
Compound 225: m.p. 117-119° C. δppm 7.72 (d, 2H), 7.39 (d, 2H), 7.10 (s, 2H), 6.41 (t, 1H), 6.17 (s, 1H), 4.66 (d, 2H), 4.44 (t, 2H), 4.31 (t, 2H), 3.59 (s, 3H).
Compound 235: oil. δppm 7.58 (d, 2H), 7.39 (t, 2H), 7.28 (t, 1H), 7.11 (s, 2H), 6.38 (t, 1H), 4.66 (d, 2H), 4.44 (t, 2H), 4.23 (t, 2H), 3.71 (s, 3H), 2.14 (s, 3H).
Compound 247: oil. δppm 7.67 (d, 2H), 7.31 (d, 2H), 6.96 (s, 2H), 6.27 (t, 1H), 5.96 (s, 1H), 4.63 (d, 2H), 4.20 (t, 2H), 3.99 (t, 2H), 3.63 (s, 3H), 2.02 (m, 4H).
Compound 248: oil. δppm 7.68 (d, 2H), 7.45 (d, 2H), 7.33 (d, 2H), 7.01 (s, 1H), 6.33 (t, 1H), 5.71 (s, 1H), 4.64 (d, 2H), 3.97 (t, 2H), 3.68 (t, 2H), 3.56 (s, 3H), 1.94 (m, 4H).
Compound 257: oil. δppm 7.56 (d, 2H), 7.34 (t, 2H), 7.22 (t, 1H), 6.93 (s, 2H), 6.22 (t, 1H), 4.62 (d, 2H), 4.16 (t, 2H), 4.01 (t, 2H), 3.69 (s, 3H), 2.13 (s, 3H), 2.04 (s, 4H).
Compound 268: oil. δppm 7.43 (m, 5H), 6.84 (s, 2H), 6.15 (t, 1H), 5.68 (s, 1H), 4.60 (d, 2H), 4.43 (t, 2H), 4.18 (t, 2H), 3.77 (s, 3H), 2.32 (m, 2H).
Compound 269: m.p. 63-64° C. δ7.46 (d, 2H), 7.35 (d, 2H), 6.84 (s, 2H), 6.11 (t, 1H), 5.77 (s, 1H), 4.58 (d, 2H), 4.50 (t, 2H), 4.15 (t, 2H), 3.81 (s, 3H), 2.32 (m, 2H).
Compound 350: oil. δppm 7.49 (m, 3H), 7.45 (m, 2H), 6.96 (s, 1H), 6.92 (s, 1H), 4.48 (m, 2H), 4.17 (m, 2H), 3.64 (s, 3H), 2.31 (m, 2H), 1.88 (s, 3H), 1.25 (s, 3H).
Compound 352: oil. δppm 7.30 (m, 2H), 7.18 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.49 (t, 2H), 4.17 (t, 2H), 3.60 (s, 3H), 2.32 (m, 2H), 1.85 (s, 3H).
Compound 356: oil. δppm 7.22 (m, 2H), 6.98 (m, 2H), 6.84 (s, 2H), 6.11 (t, 1H), 4.58 (d, 2H), 4.46 (t, 2H), 4.17 (t, 2H), 4.06 (m, 2H), 3.42 (s, 3H), 2.32 (m, 2H), 1.86 (s, 3H), 1.45 (m, 3H).
Compound 360: oil. δppm 7.52 (m, 1H), 7.33 (m, 1H), 7.18 (m, 1H), 6.82 (s, 2H), 6.10 (t, 1H), 4.56 (d, 2H), 4.45 (t, 2H), 4.15 (t, 2H), 3.47 (s, 3H), 2.31 (m, 2H), 1.74 (s, 3H).
Compound 361: oil. δppm 7.55 (m, 1H), 7.41 (m, 1H), 7.16 (m, 1H), 6.84 (s, 2H), 6.11 (t, 1H), 4.58 (d, 2H), 4.49 (t, 2H), 4.17 (t, 2H), 3.62 (s, 3H), 2.32 (m, 2H), 1.86 (s, 3H).
Compound 363: oil. δppm 7.25 (m, 2H), 6.98 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.47 (t, 2H), 4.17 (t, 2H), 3.86 (s, 3H), 3.61 (s, 3H), 2.32 (m, 2H), 1.86 (s, 3H).
Compound 367: oil. δppm 7.28 (d, 2H), 7.21 (d, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.60 (d, 2H), 4.47 (t, 2H), 4.17 (m, 2H), 3.61 (s, 3H), 2.42 (s, 3H), 2.32 (t, 2H), 1.86 (s, 3H).
Compound 368: oil. δppm 7.21-7.31 (m, 4H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.47 (t, 2H), 4.17 (t, 2H), 3.62 (s, 3H), 2.71 (m, 2H), 2.32 (m, 2H), 1.87 (s, 3H), 1.28 (t, 3H).
Compound 376: oil. δppm 7.12 (s, 1H), 7.06 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.57 (d, 2H), 4.47 (t, 2H), 4.19 (t, 2H), 3.43 (s, 3H), 2.38 (s, 3H), 2.30 (t, 2H), 2.10 (s, 3H), 1.73 (s, 3H).
Compound 377: oil. δppm 7.24 (m, 1H), 7.07 (m, 2H), 6.84 (s, 2H), 6.11 (t, 1H), 4.58 (d, 2H), 4.49 (t, 2H), 4.17 (t, 2H), 3.62 (s, 3H), 2.34 (s, 6H), 2.32 (m, 2H), 1.86 (s, 3H).
Compound 378: oil. δppm 7.17 (m, 2H), 6.96 (s, 1H), 6.84 (s, 2H), 6.10 (t, 1H), 4.57 (d, 2H), 4.48 (t, 2H), 4.18 (t, 2H), 3.43 (s, 3H), 2.34 (s, 3H), 2.32 (m, 2H), 2.08 (s, 3H), 1.73 (s, 3H).
Compound 387: oil. δppm 7.31 (d, 2H), 7.23 (d, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.48 (t, 2H), 4.17 (t, 2H), 3.63 (s, 3H), 2.93 (m, 1H), 2.32 (m, 2H), 1.87 (s, 3H), 1.31 (s, 3H), 1.28 (s, 3H).
Compound 389: oil. δppm 7.46 (m, 2H), 7.25 (m, 2H), 6.84 (s, 2H), 6.12 (t, 1H), 4.58 (d, 2H), 4.46 (t, 2H), 4.18 (t, 2H), 3.62 (s, 3H), 2.31 (m, 2H), 1.88 (s, 3H), 1.36 (s, 9H).
Compound 423: oil. δppm 7.42 (d, 2H), 7.34 (d, 2H), 6.88 (s, 1H), 6.19 (t, 1H), 5.73 (s, 1H), 4.68 (d, 2H), 4.39 (t, 2H), 4.15 (t, 2H), 3.71 (s, 3H), 2.31 (m, 2H).
Compound 443: oil. δppm 7.30 (m, 3H), 7.21 (d, 2H), 6.31 (t, 1H), 4.76 (d, 2H), 4.35 (t, 2H), 4.11 (t, 2H), 3.55 (s, 3H), 2.40 (s, 3H), 1.80 (s, 3H).
Compound 444: oil. δppm 7.31 (d, 2H), 7.24 (d, 2H), 7.16 (s, 1H), 6.29 (t, 1H), 4.76 (d, 2H), 4.34 (t, 2H), 4.11 (t, 2H), 3.55 (s, 3H), 2.68 (m, 2H), 2.23 (q, 2H), 1.80 (s, 3H), 1.26 (t, 3 H).
Compound 499: oil. δ 7.44 (m, 3H), 7.32 (d, 2H), 6.96 (s, 2H), 6.27 (t, 1H), 4.63 (d, 2H), 4.45 (t, 2H), 4.28 (t, 2H), 3.57 (s, 3H), 1.82 (s, 3H).
Compound 500: m.p. 82-83° C. δppm 7.48 (s, 4H), 7.03 (s, 2H), 6.35 (t, 1H), 5.78 (s, 1H), 4.65 (d, 2H), 4.40 (t, 2H), 4.24 (t, 2H), 3.69 (s, 3H).
Compound 516: oil. δppm 7.27 (m, 2H), 7.18 (m, 2H), 6.85 (s, 2H), 6.12 (t, 1H), 4.59 (m, 4H), 4.36 (m, 2H), 3.60 (s, 3H), 2.41 (s, 3H), 1.87 (s, 3H).
Compound 518 (DMSO): oil. δppm 7.30 (m, 2H), 7.23 (m, 2H), 7.05 (s, 2H), 6.38 (m, 1H), 4.65 (m, 2H), 4.45 (m, 2H), 4.27 (m, 2H), 3.55 (s, 3H), 2.68 (m, 2H), 1.80 (s, 3H), 1.27 (m, 3H).
Compound 522: oil. δppm 7.43 (s, 4H), 6.94 (s, 2H), 6.24 (t, 1H), 5.65 (s, 1H), 4.63 (d, 2H), 4.17 (t, 2H), 3.98 (t, 2H), 3.69 (s, 3H), 1.96 (s, 4H).
Compound 532: oil. δppm 7.45 (m, 3H), 7.31 (d, 2H), 6.95 (s, 2H), 6.27 (t, 1H), 4.63 (d, 2H), 4.19 (t, 2H), 3.99 (t, 2H), 3.56 (s, 3H), 1.96 (s, 4H), 1.82 (s, 3H).
Compound 538 (DMSO): oil. δppm 7.26 (m, 2H), 7.19 (m, 2H), 7.03 (s, 2H), 6.36 (m, 1H), 4.64 (m, 2H), 4.17 (m, 2H), 3.98 (m, 2H), 3.53 (s, 3H), 2.38 (s, 3H), 1.94 (m, 4H), 1.79 (s, 3H).
Compound 540: oil. δppm 7.27 (m, 4H), 6.85 (s, 2H), 6.13 (t, 1H), 4.58 (m, 2H), 4.29 (m, 2H), 4.04 (m, 2H), 3.62 (s, 3H), 2.71 (m, 2H), 2.03 (m, 2H), 1.87 (s, 3H), 1.29 (t, 3H).
Compound 546: oil. δppm 7.58 (s, 1H), 7.56 (d, 2H), 7.50 (s, 1H), 7.38 (d, 2H), 6.84 (s, 2H), 6.10 (t, 1H), 4.59 (d, 2H), 4.24 (t, 2H), 4.14 (t, 2H), 2.27 (q, 2H).
Compound 547: oil. δppm 7.64 (d, 2H), 7.58 (s, 1H), 7.50 (s, 1H), 7.27 (d, 2H), 6.84 (s, 2H), 6.10 (t, 1H), 4.59 (d, 2H), 4.24 (t, 2H), 4.14 (t, 2H), 2.28 (q, 2H).
Compound 550: oil. δppm 7.76 (d, 2H), 7.65 (s, 1H), 7.29 (d, 2H), 6.38 (s, 2H), 6.10 (t, 1H), 4.56 (d, 2H), 4.44 (q, 2H), 4.33 (t, 2H), 4.19 (t, 2H), 2.35 (q, 2H), 1.41 (t, 3H).
Compound 551: oil. δppm 7.32 (s, 1H), 7.29 (d, 2H), 7.28 (s, 1H), 7.26 (d, 2H), 6.83 (s, 2H), 6.11 (t, 1H), 4.59 (d, 2H), 4.42 (q, 2H), 4.29 (t, 2H), 4.18 (t, 2H), 2.35 (q, 2H), 2.22 (s, 3H), 1.41 (t, 3H).
Compound 2 and other components are fully mixed, after smashing through ultrafine pulverizer, 30% compound 2 wettable powders products were obtained.
Fully mixing compound 367 and other components, suspension concentrate can be obtained, and then any required concentration dilution can be obtained by diluting the above obtained concentrated suspension with water.
To mix compound 367 and other components, after smashing, kneading together with water, added to the granulation 10-100 mesh machine for granulation, then by drying and sieving (at the scope screen).
To determine the insecticidal and acaricidal activity of selected compounds by the following procedures:
Compounds were dissolved in mixed solvent (acetone:methanol=1:1), and diluted to required concentration with water containing 0.1% of tween 80.
The second instar larvae of diamond backmoth (Plutella xylostella) were used in biological test. The method of spraying by airbrush was employed.
Determination of insecticidal activity against diamond backmoth: The cabbage leaves were made into plates of 1 cm diameter by punch. A test solution (0.5 ml) was sprayed by airbrush at the pressure of 0.7 kg/cm2 to both sides of every plate. 10 Second instar larvae were put into the petri-dishes after the leaf disc air-dried and 3 replicates were set for each treatment. Then the insects were maintained in observation room (25V, 60-70% R.H.). Scores were conducted and mortalities were calculated after 72 hrs.
Parts of test results are as follows:
At the dose of 100 mg/L, compound 1, 2, 8, 11, 13, 16, 17, 18, 24, 26, 38, 76, 77, 86, 92, 225, 247, 248, 257, 268, 269, 278, 280, 283, 284, 293, 306, 352, 356, 360, 361, 363, 367, 368, 377, 387, 389, 500, 522, 532, 538, 546 showed 100% control of the second instar larvae of diamond backmoth. At the same dose, contrast compound pyridalyl also showed 100% control.
At the dose of 25 mg/L, compound 2, 225, 247, 248, 268, 269, 352, 367, 377, 387 showed 100% control of the second instar larvae of diamond backmoth. At the same dose, contrast compound pyridalyl also showed 100% control.
At the dose of 6.25 mg/L, compound 2, 248, 367, 377, 387 showed above 80% control of the second instar larvae of diamond backmoth and compound 2, 367 showed more than 90% control. At the same dose, contrast compound pyridalyl also showed 65% control.
Determination of fungicidal activities against plant diseases of selected compounds were carried out by the following procedure:
Determination of Fungicidal Activity In Vivo:
Plants were prepared in pot. Compounds were dissolved in acetone and diluted to required concentration by water containing 0.1% (wt) Tween80. Test solution was sprayed onto potted plant. Pathogen inoculation was carried out after 24 hours, then plants were hold in growth chambers maintaining constant temperature and moisture for infection. When untreated plant was under desirable disease severity (after 1 week approximately), assessment was carried out by visual observation.
Part of Test Results In Vivo:
At 400 ppm, compound 2 showed more than 70% control of wheat powdery mildew.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2008 1 0227711 | Nov 2008 | CN | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/CN2009/075131 | 11/25/2009 | WO | 00 | 3/28/2011 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2010/060379 | 6/3/2010 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 6949551 | Tiebes et al. | Sep 2005 | B2 |
| 20040029886 | Tiebes et al. | Feb 2004 | A1 |
| 20090192208 | Takyo et al. | Jul 2009 | A1 |
| 20110178149 | Liu | Jul 2011 | A1 |
| Number | Date | Country |
|---|---|---|
| 1761654 | Apr 2006 | CN |
| 1914178 | Feb 2007 | CN |
| 0787710 | Aug 1997 | EP |
| 9611909 | Apr 1996 | WO |
| 9611909 | Apr 1996 | WO |
| 2005019147 | Mar 2005 | WO |
| 2010060379 | Jun 2010 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20110178149 A1 | Jul 2011 | US |
