2-QUINOLINONE DERIVATIVES

Abstract: The present invention relates to novel 2-quinolinone derivatives of general formula (I) useful in agriculture, especially as fungicides but also as insecticides and miticides, wherein R1, R2, R3 and R4 are independently hydrogen, halogen, C1-C10 alkyl, branched C3-C4 alkyl, C1-C3 haloalkyl, C1-C8 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, NO2, CN, alkoxy carbonyl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzenesulfonyl, benzyl, substituted benzyl or morpholine; R5 is C1-C6 alkyl, branched C3-C6 alkyl, C3-C6 cycloalkyl, phenyl, substituted phenyl, benzyl or phenylthio methyl; and X is S(O)nR6, OR9 or NAB; wherein n is 0 or 1; R6, R9, A and B are defined within the description.

Description: 2-QUINOLINONE DERIVATIVES BACKGROUND OF THE INVENTION Feild of the Invention The present invention relates to novel 2-quinolinone derivatives of the following general formula(I) useful in agriculture, especially as fungicides but also as insecticides and miticides. wherein, Rj, R 2 , R j and R 4 are independently hydrogen, halogen, C j -C 10 alkyl, branched C 3 -C 4 alkyl, C.-G. haloalkyl, C r C g aikoxy, C.-C 3 haloalkoxy, Q-G* alkylthio, C r G* haloalkylthio, NO z , CN, aikoxy carbonyl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzenesulfonyl, benzyl, substituted benzyl or morpholine ; R j is C,-C 8 alkyl, branched G j -C 8 alkyl, G j -C 6 cycloalkyl, phenyl, substituted phenyl , benzyl or phenylthio methyl ; and X is S(0)nR 6 , OR 9 or NAB ; wherein, n is 0 or 1 ; R 6 is R 7 or R g , and then R, is C,-C 6 alkyl, branched C 3 -C 6 alkyl, C j -C 3 haloalkyl, benzyl or substituted benzyl, and R g is phenyl, substituted phenyl, benzyl or substituted benzyl ; R, is C 2 -C 5 alkyl, branched -C, alkyl, C 5 -C 6 cycloalkyl, phenyl or substitut phenyl ; A and B arc combined together to form a saturated or unsaturated 5 or 6-membe cyclic ring or fused ring, optionally including a hetero atom selected from or N, or optionally substituted with C J -G J alkyl or carbocyclic ring including atom, or one of A and B is H and the other is R 10 or Z-Ar ; and then, R 10 is saturated or unsaturated Cι-C- 0 alkyl, branched C 3 -G alkyl or C 3 -C 6 cycloalk optionally including a hetero atom selected from O, S or N or optionall substituted with C^ alkyl or alkoxycarbonyl, - haloalkyl, alkoxyalky alkoxycarbonylalkyl, phenyl, substituted phenyl, pyridyl, substituted pyridy pyrimidyl, or substituted pyrimidyl ; Z is C j - alkyl chain, optionally containing cyclopropylene ring, or optionall substituted with -G j alkyl, C j - aikoxy, C^G j hydroxyalkyl or phenyl ; and AT is C 3 -C 6 cycloalkyl, optionally including a nitrogen atom, or pyridyl, substitute pyridyl, or a phenyl group of the following formula(II) wherein, R JJ , R E , Rj 3 , R I4 and R^ are independently H, halogen, C-.-C 6 alkyl, branched C 3 -C alkyl, C j -Q, haloalkyl, C r C 4 aikoxy, phenyl, phenoxy, phenylthio, CN, N0 2 NH 2 , or S0 2 NH 2 . Description of the Prior Art There is an acute need for new fungicides, insecticides, and miticides, becaus target pathogens are rapidly developing resistance to currently used pesticides. Th development of resistance to some of the fungicides in current use, such as th triazoles, the benzimidazoles, the acylalanines, and the organophosphates and th insecticides, such as the carbamates, the organophosphates, and the pyrethrσids, is well known. Therefore a need exists for new fungicides, insecticides, and miticides. SUMMARY OF THE INVENTION The present invention relates to novel 2-quinolinone derivatives having the above general formula(I), which have fungicidal and insecticidal activity. DETAILED DESCRIPTION OF THE INVENTION The compounds of the general formula(I) according to the present invention can be prepared by reactions as described herein below. The compounds(Ia) of general formula(I) wherein X is SR 6 , and then R 6 is R-,, can be made by thermally cyclizing compounds of following formula(III), and the compounds(Ib) of general formula(I) wherein X is SORg, and then R g is R-,, may be prepared by oxidizing the corresponding compounds (la) using a conventional oxidation procedure. wherein, R R 2 , Rg, R 4 , R 5 and R, are as previously defined. The above reaction may be carried out without solvent or under the presence of solvent, for example, hydrocarbon solvents such as paraffin oil, benzenes such as xylene and dichlorobenzene, amides such as dimethyl formamide and dimethyl acetamide, anilines such as N,N-dimethylaniline and N,N-diethyl aniline, ethers such as diphenyl ether, or a mixture of them. The cyclizing reaction is carried out at 140 ~ 250 3 , preferably 160 ~ 200 , . If the temperature is lower than 140 _ , the reaction rate is very slow, and if higher than 25012 , it is attended with the severe evolution of mercaptan(R 7 SH) as a by¬ product. Alteratively, the compounds(Ia') of general formula(I) wherein X is SR g , and then R 6 is R g , can be manufactured by reacting the compounds of above foraιula(Ib) with thiol of following formuIa(IV), and the compounds(Ib') wherein X is SOR 6 , and then Rg is Rg, can be prepared by oxidizing the corresponding compounds(Ia') using conventional oxidation procedure. wherein, R,, _, R 3 , R 4 , R. and R g are as previously defined. The compounds of above formula(Ia') can be prepared by the substitution reaction heating 4-alkylsulfoxyquinolinone of the above formula(Ib) and thiopheno derivative of the above formula(IV) without solvent or under the presence of solvent, and then the solvent as the above, e.g. hydrocarbons, benzenes, amides, anilines, ethers, or their mixture, may be used. The substitution reaction is carried out at 100 ~ 25012 , preferably 160 - 200 12. If the temperature is lower than 10012 , the reacting rate is very slow, and if higher than 250 , the yields are very low. The compounds (when n in X of formula(I) is 1 ) of the formula(Ib) and (lb' ) can be prepared by oxidation of the compounds (when n in X of formula(I) is 0 ) o the formula(Ia) and (la') using a conventional oxidants, for example, organic or inorganic peroxy compounds such as hydrogen peroxide, potassium peroxymonosulfate, tertiary butyl hydroperoxide, m-chlσro peroxybenzoic acid, peroxyacetic acid, and magnesium monoperoxyphthalate. And then, solvent may be used as followings ; water ; hydrocarbon halide such as dichloromethane, chloroform, carbon tetrachloride, and chlorobenzene ; aliphatic acid such as acetic acid and propionic acid ; or alcohols such as methyl alcohol, ethyl alcohol, etc. The reaction may b e carried out at 0 - 130 , preferably 20 ~ 6012 , and then if the temperature is lower than 012 , the reaction rate is very slow, and if higher than 13012 , the used solvent may be boiled over. The amount of used oxidant may be usefully 1.2 fold or more with the used compound of the formula(Ia) or (la'), but it is not limited specially. The quinolinone derivatives of the formula(Ia) and (lb 1 ) and sulfoxy-2- quinolinone derivatives may be optionally recrystallized or purified by chromatography. The compounds(Ic) of general formula(I) wherein X is OR, and then R, is methyl can be prepared by the known process described in J. Org. Chem. Vol. 31 , P1276-1278(1966) or I Org. Chem. Vol. 34, P2183-2187(1969) by J. W. Huffman and J. H. Cecil. Especially, 3-isobuty_yl-4-methoxy-(2H)quinolinone, 3-isobutyryl- 4,8-d_methoxy-2(lH)-quinolinone, 3-isovale_yl-4-methoxy-2(lH)-quinolinone or 3- isovaleryl-4,8-dimethoxy-2(lH)-quinolinone were prepared in 14 - 18% yields by reacting the corresponding 3-acyl-4-hydroxy-2(lH)-quinolinone with diazomethane, and separation of the resulted mixture of 2(lH)-quinolinone, l-methyl-2(lH)- quinolinone and other products as using liquid chromatography. In this invention, the compounds(Ic) of general formula(I) wherein X is OR 9 were made by condensing the compounds of formula(Ib) with an alcohol of the for ula(V). HOR, ( V ) wherein, R j , R^ R 3 , R * ,, R j and R, are as previously defined. Also, the above compound(Ic) may be prepared by substitution of alcohols(R 9 OH) under heating without solvent or under the presence of a solvent, or directly using alcohol as a solvent, and then the base may be used or not. The used solvent may be, excepting alcohol used as a reactant, dimethyl formamide, acetonit-ile, dioxane, benzene, toluene, xylene, tetrahydroftiran, hexane, heptane, or a mixture of them. The base may be, for example, pyridine, triethylamine, N,N-dialkylaniline, alkalimetal hydroxide, alkalimetal carbonate, metal hydride, etc. The substitution reaction is carried out at boiling point of solvent or between room temperature and 200 2 , preferably at 50 ~ 12012. The compounds(Id) of general formula(I) wherein X is NAB and then NAB is NMe 2 can be prepared by the known process described in Helv. Chim. Acta., Vol. 52, P 2641 ~ 2657(1969) by H. J. Gais, K. Hafmer and M. Neuensch wander. Especially, 3-ace.yl-4,8-(dimethylamino)-2(lH)-quinolinone may be obtained by reaction of phenyiisocyanate and l-dimethylamino-3-oxo-l-butylene according to [4+ 2] cycloaddition. In this invention, the compounds(Id) of general formula(I) wherein X is NAB were prepared by condensing the compounds of formula(Ib) with the amines of the formula(VI) HNAB VI ) wherein, R 15 1^, 1^, R 4 , R j , A and B are as previously defined. The above compounded) can be prepared by reacting 4-alkylsulfoxy-2- quinolinone of the above formula(Ib) with an amine compound of the following formula(VI) under the presence of inert solvent. When the amine compound of foraιula(VI) is acid salt, an acid remover for example, trialkylamines (such as triethylamine), potassium carbonate, inorganic base (such as sodium hydroxide), may be used, as adding 1 ~ 2 equivalents, and thereafter acid adding salt of amine compound is added. An inert solvent used in the present invention may be, for example, ethers such as diethylether, diisopropyl ether, tetrahydrofuran, dioxane, diphenylether, etc. ; hydrocarbons such as benzene, toluene, xylene, ligroine, etc. ; hydrocarbon halides such as dichloroethane, chloroform, carbon tetrachloride, etc. ; esters such as ethyl acetate, ethyl propionate, etc. ; chlorobenzenes such as monochlorobenzene, dichlorobenzene, etc. ; aprotic polar solvents such as N,N -dimethyl formamide, dimethyl sulfoxide, etc., but the above reaction may be caπied out without solvent. According to the present invention, pyridine or trialkylamine may be used as two purposes of a base and a solvent. The reaction can be carried out at 0 ~ 260 12 , preferably between room temperature and boling point of the solvent, and then the reacting time is preferable of 0.5 ~- 8hr but it is affected by the reaction temperature. As a result of the reaction, when the amine compound of formula(VI) bein not acid adding salt is used, the crude product is obtained by evaporating the solvent under the reduced pressure. But, when the amine compound of formula(VI) being acid adding salt is use the crude product may be obtained by following process ; the solvent is evaporate under the reduced pressure ; water is added to dissolve the salts ; the resulting mixtu is extracted with water-insoluble organic solvent such as methylenechloride chloroform, ethyl acetate, etc. ; and the organic layer is evaporated under the reduce pressure to afford the crude product The obtained 2-quinolinone derivatives of formula(Id) may be purified b column chromatography or recrystallized by the following solvent ; alcohol solven such as methanol, ethanol, etc. ; ester of organic acid such as ethyl acetate, methy acetate, etc. ; hydrocarbon solvent such as pentane, hexane, etc. ; ether such as ethylether, tetrahydrofuran, etc. On the other hand, the starting material used in the present invention, keten dithio acetal a -anilide of the formula(III), can be prepared from β-ketoanilide by th following reaction process wherein, R, , R 2 , R 3 , R 4 , R 5 and R 7 is respectively as the above defined, Y is chlorine, bromine, iodine, or alkyl or arylsulfonate. The compounds according to the present invention have highly curative an protective fungicidal activity for plant germs of widely spectrum as followings ; fo example, rice blast(PMcularia oryzae), rice sheath blight(i?/iizocta__ia solani) cucumber gray mold(_Sσt_yt s cineτ&a), cucumber powdery mildew (Sphaewthec fαligiπea), cucumber downy mildew (Pseudoperonospora cubensis), grape down rnildew(Pi_-S-_ιopαra viticola), tomato late b]i t(Phytophtiιora infestans), rice brown spot(Cochliobolus miyabeanus), peanut brown leaf spot(Cfercσspora arachidicola), barley powdery mildew (Erysiphe graminis), wheat leaf rust (Puccinia iecondita), wheat stem nist(_P__cc___i_. gramims), and wheat eye spot (Pseudoceicospoiella herpotrichoides). Also, the compounds according to the present invention have highly insecticidal activity for noxious insects, for example, house fly, mosquito, cockroach and agricultral insects, for example, Hemiptera such as small brown plant hopper( aodeρ_-_-X striatellus Fallen), brown plant hopper(Map__rv__ta lugens Stail), white-backed rice plant hopper (Sogatella ήπcifera Horvath), green rice leaf hopper(Nep__otett- : cincticeps UMer), greenhouse whitefly(rri__feurode_. vaporaπomw Westwood), and green peach aphid( yz_.s peiήcae Sulzer) ; Lepidoptera such as apple leaf miner (Phyllonorycter ringoπiella Matsumura), diamond-back moth (Plutella xylostella Curtis), rice armyworm (Pseuclaletia separata Walker), cabbage armyworm(M__meso_i brassicae Linnaeus), tobacco cutwoτm(Spodoptera Htura Fablicius), and common cabbage worm (Aeris rapae Linnaeus) ; Coleoptera such as rice leaf beetle (Oulema oryzae Kuiwayama), and rice- plant weevil rice curculio(Ec_-i-i_>cπeπιus squameus Billbery) Useful formulations of the compounds of formula(I) can be prepared by mixing the compounds of active ingredient of about 0.01 ~ 90 weight % with proper solid or liquid carrier and supporters such as surfactant, diluent, spreader, synergist, adhesive, dispersant, etc. The used solid carrier may be usually chosen from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates, and liquid carrier may be water, alcohol, methanol, ethanol, acetone, dimethylformamid ether, benzene, xylene, toluene, naphtha, etc. Surfactant may be nonionic surfactant(e.g., polyoxy ethylene alkylphenylethe and poly oxyethylene fatty acid ester), anionic surfactant(alkyl benzenesulfonic acid lignine sulfonate and dinaphthalene methane sulfonate), etc. Poly vinylalcohol, CMC gum arabic, etc. may be used as adhesive. The fungicidal and insecticidal compositions using the compounds of th present invention may be manufactured as formulation such as powder, wettabl powder, granules, emulsifiable concentrates, suspensions, solution, fumigant, ga phase, etc., and their formulations were used in earth, agriculural products, seedling seeds, etc. For example, emulsifiable concentrates or solution may be prepared b uniformly dissolving the compound of formula(I) with hydrocarbon, acetone o alcohol and surfactant. Wettable powders, which may be compacted to form water dispersibl granules, comprise an intimate mixture of the active compound, inert carrier an surfactants. The combinations including the compounds according to the present inventio may be used by mixing with agricultural chemicals such as insecticides, fungicides herbicides, plant growth regulants, miticides, etc. Especially, since the known fungicides have resistance, the compounds o formula (I) of more than 1 weight % may be used with the known fungicides including following compounds ; 1) N-substituted azoles, for example, prochloraz, triademefon, and flusilazol ; 2) pyrimidines, such as fenarimol and nuarimol ; 3) morpholines, such as fenpropimorph and tridemorph ; 4) piperazines, such as triforine ; 5) pyridines, such as pyrifenox ; 6) dithiocarbamates, such as maneb and mancozeb ; 7) phthalimides, such as captafol ; 8) isophthalonitriles, such as chlorothalonil ; 9) dicarboximides, such as iprodione ; 10) benzimidazoles, such as benomyl and carbendazim ; 11) 2-aminopyrimidines, such as ethirimol ; 12) carboxamides, such as carboxin ; and 13) dinitrophenols, such as dinocap. The fungicide combinations of the invention contain at least 1% , generally 20 ~ 80% by weight of a compound of formula (1). The compounds of said formula(I) according to the present invention specify as the following Tables 1 ~ 4 ; Table 1. : 4-alkyl or arylthio-2-quinolinone(I-a, I-a') and 4-alkyl or arylsulfoxy-2 quinolinone(I-b, I-b') Comp.No. R, R 2 R 3 R 4 R j R g n m.p.(t2) Table 2.4-alkoxy or 4-aιyloxy-2-quinolinone(Ic) Comp.No. R x R j R. R 4 R, m.p.( _) CR C Cl CF, Table 3. 4-amino-2-quinolinone(Id) Comp.No. R, R j R 3 R 4 R 5 NAB m.p_(t) 243 H Cl H CF 3 C 244 248 H 250 Cl CR 251 254 H NHC 146-150 255 NHC2H 5 256 H N ^ 151-153 261 262 Comp.No. R, R. R, R 4 R. NAB m.p.rø 27 Comp.No. R* R 2 R j R. NAB m.p.(t2) H Cl CR HN-^ * -^ 224-229 HN * 191-200 HN" -@-Cl 217-220 Q H HN- 259-262 H CF, Hr λ-α 190-193 HN Ύ' 216-218 Comp.No. R j R j R. R_ 5 NAB m.p.( _) l HN' .OCH, 205-209 OCH, CR 135-137 Ph 164-166 ■ ^- ι 180-183 Cl 118-120 \__ * 35. Comp.No. R j R 2 Ra R, Rs NAB m.p.CC) CH, H CH, --C . H- α 548 549 550 Cl H 558 NO. OCH. " 559 Comp.No. R j R- R, R_ R5 NAB m.p.( 2) 602 H Cl H CF 3 CH 3 216-217 609 CH, Cl HN ~@-C1 173-175 610 HN-^" 103-105 61 1 149-150 612 HI-T ^^-CI 248-251 616 HN'^' 128-130 617 HN-^^ 135-136 Comp.No. R. 1FL. R, R_ R* NAB m.p.(2) H α ci Comp.No. R, R 2 R 3 R R5 NAB m.p.CC) H H H C j HN"^.^^-C1 293-294 295-296 HN- ^ "Cl 238-240 NO. ci CH j -_-N-_v ~ cH 3 219-220 HN^^" 187-188 Cl Cl Cl CR, 145-147 HN 135-136 Cl Cl H HN >260 HN- 166-168 220-222 HN-^-^-Z N Comp.No. R j J R 3 R_ Rs NAB m.p.(t.) 827 H H Cl Cl CR* 828 829 830 CR H Cl 834 H— (Q) > 260 - _ CF3 835 ' " " NH -—ZaQ>) 268-269 r 837 " " NH— Q} 171-172 838 " " NH — δV——^H ~ sf 1 198-199 •*. Comp.No. R, R^ R 3 R 4 R 5 NAB m.p.(T2) 840 " NH— <3)— 6 H i3 "n 183-185 «_H. 843 " \_ 208-209 845 Cl " NH '-—< (δO>^ 204-205 C Cll 846 NH— /Q 253-254 847 " NH"" \Q/ " ~ "CI 227-229 851 MH— @ _-f* 249-250 Comp.No. R. R j . ' R 3 R 4 Rj NAB m.p.CC ) Cl 852 H Cl H Cl CH. r-l 2AA-2A5 NH t--©- C! 853 CF 3 CA NH — < 154-155 854 CH 3 CH- NH -® 220-221 _ oc~3 858 " " " " " NH >—-<θ>>> 197-199 NH— (θ 861 " H " " ^-S 162-163 Cl NH >-- <c w 862 ' " ^Z>/> 164-165 NH— ®- Cl 863 " X 231-232 864 " 144-145 Comp.No. R, R, R 3 R 4 R j NAB m.p.(C) CH3 865 " " NH >-—< (oO$) 144-145 869 Cl CF 3 CA 84-85 870 " H " " CH 3 /-v 165-166 ^ NH- /ΛX Cl 85 NH-^-Cl 190-191 877 " NH cι 168-169 Comp.No. R J R- R R 4 ^ NAB m.p.CC) F 878 H H H CF 3 CR \_ 162-163 N -< >; λ — ' 879 " F " CH 3 " NH— θ 162-163 881 NH — (Q— cl 163-164 H— -CF, 886 " ^v___y 169-170 Cl 887 " H M C 6 H 5 " NH -— 0>> 167-168 NH— (θ) 888 " " " " " > — / 209-211 NH— (θ - Ci 889 " " " " " 206-207 Cl 890 " " " " " NH— 0/ 204-206 Comp.No. R, R^ R 3 R 4 R^ NAB m.p.CC) . cOCH j 892 " NH -— (o0>> 183-186 NH— (θ 895 Cl α " Cl " ^-s 217-218 901 CH- R; 902 903 Comp.No. R j R- R 3 R 4 ζ NAB m.p.(C) Cl 904 H H H CH- H s CH 3 \__ 128-130 _ -§-.cι 905 N0 2 " " Cl " NH— p)— CF 238-239 Cl 907 " " " " " NH —/θ>— Cl 210-213 911 " " " " " NH—<π> 293-295 Cl 914 " " " " " H - — CO/ 216-217 Cl 915 " " " " " H— Q> 222-223 -^ 916 " " " " " 204-205 Comp.No. R, R- R 3 R 4 ΕL- NAB m.p.(C ) 917 " ' " NH— g 262-263 NH- Cl 919 NJti- 254-256 Cl 920 > 260 Cl 921 NH [ --^ter Cl - ( > 260 NH "^CF_ 927 Cl " 232-233 928 " Cl H CF 3 CA " 113-115 929 " H " ' * CH 3 " 151-152 Comp.No. R, R j R 3 R 4 R. NAB m.p.CC) 930 Cl Cl Cl H CH, NH- 'CF, 272-273 tt 931 H F H CF, 156-157 NH— < 932 125-130 NH 933 160-161 934 H NH- 209-210 936 Cl Cl C-E j NH- 'CF- 238-239 NH— 939 940 CH. 1 > 260 942 i-C NH -< 103-104 Comp.No. R, R j R 3 R 4 Rj NAB m.p.(C) 943 NH— ©— C1 130-131 944 NH Cl -< 129-130 945 NH -®- Cl 163-164 946 NH CF, 119-121 947 " " 98-100 948 " * ii-CCA_R 114444--1146 949 " M . 134-137 NH — *ζ 950 " H F CH 3 CH 3 «» 211-213 952 " NH / ^ CF» 237-238 953 Cl " H " NH— < EXAMPLE 1 : 3-Acetyl-4-methylthio-2-quinolinone (1) N-Phenyl-ff -(bismethylthioylidene)acetoacetamide(28.1 g, 0.1 mol) was heated and refluxed for 2hr in solvent of dichlorobenzene(300 ml) imtill the evolution of methylmercaptane ceased. The reaction progress was determined by chromatography. When the reaction was completed, the reaction mixture was cooled, and then the precipitate was filtered to give the desired product(19.1g , yield : 82 %). Η NMR ( DMSO-d 6 ) : $ 10.7(s, 1H), 8.2 ~ 7.15(m, 4H), 2.65(s, 3H), 2.53(s, 3H). EXAMPLE 2 : 3-Acetyl-7-methoxy-4-methylthio-2-quinolinone (2) N-(m-Anisyl)-ff -(bismethylthioylidene)acetoacetamide(3.1g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product(2.1g, yield : 82%). * H NMR( CDC1 3 ) : S 10.49(s, 1H), 8.18 ~ 6.68(s, 3H), 3.8(s, 3H), 2.64(s, 3H), 2.53(s, 3H). EXAMPLE 3 : 3-Acetyl-8-chloro-4-methylthio-2-quinolinone (3) N-(2-Chlorophenyl)-ff -(bismethylthioylidene)acetoacetamide (3.2g. 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.2g, yield : 86%). Η NMR ( DMSO-d. ) : $ 8.2 ~ 7.25(m, 3H), 4.5 ~ 3.0(brs), 2.67(s, 3H), 2.59(s, 3H). EXAMPLE 4 : 3-Acetyl-5,8-d_chloro-4-me.hylthio-2-quinolinone (4) N-(2,5-Dichlorophenyl)-^ -(bismethylthioylidene)acetoacetamide (3.5g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.0g, yield : 68%). ! H NMR( DMSO-d G + CDC1 3 ) : S 1.1 (d. J=9.0, 1H) . 7.27(d, J=9.0, 1H), 2.64(s,3H), 2.52(s, 3H). EXAMPLE 5 : 3-Acetyl-6-methoxy-4-methylthio-2-quinolinone (5) N-(p-Anisyl)- -(bismethylthioyhdene)acetoacetamide (3.1g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (1.9g, yield : 74%). 1 H NMR(DMSO-d 6 ) : S 10.68(s, 1H), 7.93 ~ 6.95(m, 3H), 3.83(s, 3H), 2.63(s,3H), 2.59(s, 3H). EXAMPLE 6 : 3-Acetyl-6-fluoro-4-methylthio-2-quinolinone (7) N-(4-Huorophenyl)-ff -(bismethylthioylidene)acetθ-icetamide (3.0g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.3g, yield : 95%). » H NMR( DMSO-d 6 + CDC1 3 ) : S 8.1 - 7.2(m, 3H), 2.62(s, 3H), 2.55(s, 3H). EXAMPLE 7 : 3-Acetyl-8-fluoro-4-methylthio-2-quinolinone (8) N-(2-Fluorophenyl)-ff -(bismethylthioylidene)butyιylacetamide (3.0g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.0g, yield : 85%). H NMR( DMSO-d 6 + CDC ) : δ 6.13 ~ 7.1 (m, 3H), 2.65(s, 3H), 2.57(s, 3H). EXAMPLE 8 : 3-Butyryl-8-chloro~4-methylthio-2-quinolinone (9) N-(2-Chlorophenyl)-σ -(bismethylthioylidene)butyιylacetamide (3.4g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.5g, yield : 895). 1 H NMR(CDC1 3 ) : δ 8.7(s, 1H), 8.52 ~ 8.05(m, 1H), 7.47 ~ 6.75(m, 3H), 2.76(t, J=7.0, 2H), 2.45(s, 6H), 1.72(m, 2H), 2.45(s, 6H), 1.72(m, 2H), 0.95(t, J=7.0, 3H). EXAMPLE 9 : 3-Acetyl-8-methyl-8-methylthio-2-quinoUnone (ll) N-(o-TolyI)-α* " -(bismethylthioylidene)acetoacetamide (3.0g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.1g, yield : 88%). 1 H NMR(DMSO-d 6 ) : S 15.6(s, 1H), 8.06 ~ 7.3(m, 3H), 2.93(s, 3H), 2.69(s, 3H), 2.65(s, 3H). EXAMPLE 10 : 3-Benzoyl-8-chloro-4-methylthio-2-quinolinone (12) N-(2-Chlorophenyl)-ff -(bismethylthioylidene)ben__oylacetamide (3.8g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.6g, yield : 81%). 1 H NMR(DMSO-d 6 , GDC1 3 ) : S 8.3 ~ 7.2(m, 8H), 2.65(s, 3H). EXAMPLE 11 : 3-Acetyl-6-chloro-8-t__fluoiOethyl-4-methylthio-2-qu_nolii_one (13) N-(4-Chloro-2-trifluoromethylphenyl)-^ -(bismethylthioylidene) acetoacetamide (3.8 g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.3g, yield : 71%). * H NMR( CDC1 3 + DMSO-d 6 ) : 5 8.3(s, 1H), 8.12(s,3H), 2.67(s, 3H). EXAMPLE 12 : 3-Acetyl-8-methoxycarbonyl-4-methylthio-2-quinolinone (16) N-(2-Methoxycarbonylphenyl)-αr -(bismethylthioylidene) acetoacetamide (3.4g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.8g, yield : 99%). 1 H NMR(DMSO-d 6 + CDC1 3 ) : £ 2.6(s, 3H), 3.27(s, 3H), 4.03(s, 3H), 7.4 ~ 8.6(m, 3H). EXAMPLE 13 : 3-Acetyl-6-nitro-4-methylthio-2-quinolinone (20) N-(4-Nitrophenyl)-<* -(bismethylthioylidene)acetoacetamide (3.3g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.1g, yield : 80%). » H NMR(DMSO-d 6 + CDC1 3 ) : δ 2.57(s, 3H), 2.66(s, 3H), 8.0 ~ 8.9(m, 4H). EXAMPLE 14 : 3-Acetyl-6-chloro-7-nitro-4-methylthio-2-quinolinone (21) N-(3-Nitro-4-chlorophenyl)-<* -(bismethylt__ioylidene)acetoacetamide (3.6g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (1.8g, yield : 61 %). 1 H NMR(DMSO-d 6 + CDC1 3 ) : δ 2.43(s, 3H), 2.7(s, 3H), 7.73 ~ 8.13(m, 2H), 11.4(s, 1H). EXAMPLE 15 : 3-Acetyl-8-cyano-4-methylthio-2-quinolinone (22) N-(2-Cyanophenyl)-ff -(bismethylthioylidene)acetoacetamide (3.1g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (1.8g, yield : 73%). ι H NMR(DMSO-d 6 + CDC1 3 ) : δ 2.13(s, 3H), 2.7(s, 3H), 7.6 ~ 8.7(m, 3H). EXAMPLE 16 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-(t-butylbenzylthio)-2- quinolinone (23) N-(4-Chloro-2-trifluoromethylphenyl)-ff - [bis- (t-butylbenz ylthio)yli dene] - acetoacetamide (6.3 g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.5g, yield : 54%). l H NMR(DMSO-d 6 + CDC1 3 ) : δ 1.27(s, 9H), 2.73(s, 3H), 4.6(s, 2H), 7.35(s, 4H), 7.95(d, 1H), 8.52(d, 1H). EXAMPLE 17 : 3-Acetyl-6-t-butyl-4-methylthio-2-quinolinone (24) N-(4-t-Butylphenyl)-αr -(bismethylthioylidene)acetoacetamide (3.4g, 0.01 mol) was used, but the reaction was cairied out as the above process of example 1 to obtain the desired product (2.3g, yield : 84%). 1 H NMR(DMSO-d 6 + CDC1 3 ) : δ 1.37(s, 9H), 2.6(s, 3H), 2.63(s, 3H), 7.73(d, 2H), 8.23(s, 1H), 10.83(s, 1H). EXAMPLE 18 : 3-Acetyl-5,6,7,8-tetrachloro-4-methylt-iio-2-quinolinone (27) N-(2,3,4,5-Tetrachlorophenyl)-α -(bismethylthioylidene)acetoacetamide (3.5g, 0.01 mol) was used, butthereaction was carried out as the aboveprocess of example 1 to obtain the desired product (2.6g, yield : 74%). 1 H NMR(DMSO-d 6 + CDC1 3 ) : δ 2.43(s, 3H), 2.66(s, 3H), 7.96(s, 1H). EXAMPLE 19 : 3-AcetyI-8-t-__fluoiOmemyl-4-memylthio-2-quinolinone (29) N-(2-Trifluoromethylphenyl)-ff -(bismemylthioy_idene)acetoacetamide (3.5 g, O.Olmol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (1.9g, yield : 65%). 1 H NMR(DMSO-d 6 + CDC1 3 ) : £ 2.6(s, 3H), 2.7(s, 3H), 8.06(m, lH),8.63(m, 1H). EXAMPLE 20 : 3-Acetyl-8-fluoro-8-trifluoromethyl-4-methylthio-2-quinolinone (33) N-(4-Fluoro-2-trifluoromethylphenyl)-ff -(bismethylthioylidene)acetoacet amide (3.7 g, 0.01 mol) was used, but the reaction was cairied out as the above process of example 1 to obtain the desired product (2.5g, yield : 83%). 1 H NMR(CDC1 3 ) : £ 2.7(s, 3H), 2.97(s, 3H), 7.73 ~ 8.16(m, 1H), 15.63(s, 1H). EXAMPLE 21 : 3-Acetyl-7-fluoro-8-trifiuorome yl-4-methylthio-2-quinolinone (34) N-(2 -Tri fluo rome thyl -3- fluo roph enyl )-a - (bis met hylt hioy lidene)acetoace t amide (3.7 g, 0.01 mol) was used, but the reaction was carried out as the above v process of example 1 to obtain the desired product (2.2g, yield : 73%). 1 H NMR(CDC1 3 ) : δ 2.72(s, 3H), 2.93(s, 3H), 7.1 ~ 7.68(m, 1H), 7.83 ~ 8.1(m, 2H). EXAMPLE 22 : 3-Acetyl-6-bromo-8-trifluoromethyl-4-methylthio-2-quinolinone (35) N-4-Bromo-8-trifluoromethyl-ff -(bismethylthioylidene)acetoacetamide (4.3g, 0.01 mol) was used, but the reaction was carried out as the above process of exampb 1 to obtain the desired product (2.5g, yield : 67%). 1 H NMR(CDC1 3 ) : δ 2.7(s, 3H), 2.93(s, 3H), 8.1(s, 1H), 8.53(s, 1H), 15.6(s, 1H) EXAMPLE 23 : 3-Acetyl-6-cWoro-7-t_-fluoromemyl-4-methylthio-2-quinolinone (36) N-(3-Trifluoromethyl)-ff -(Msmemylthioylidene)acetoacet_-rnide (3.8g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (1.7g, yield : 52%). 1 H NMR(CDC1 3 ) : δ 2.7(s,3H), 2.92(s, 3H), 8.1~8.3(m, 2H), 15.57(s, 1H). EXAMPLE 24 : 3-Acetyl-6-hexyl-4-methylthio-2-quinolinone (37) N-(4-Hexylphenyl)-« -(bismethylthioylidene)acetoacetamide (3.7g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to o btain the desired product (2.5g, yield : 82%). 1 H NMR(CDC1 3 ) : δ 0.78 ~ 0.97(m, 3H), 1.16 ~ 1.8(m, 10H), 2.67(s, 3H), 2.83(s, 3H), 7.57~8.07(m, 3H). EXAMPLE 25 : 3-Acetyl-6,7,8-trifluoro-4-methylthio-2-q*ιinolinone (38) N-(2,3,4-Trifluorophenyl)-ff -(bismethylthi oylidene)acetoacetamide (3.4g , 0.01 mol) was used, but the reaction was carried out as the alsove process of example 1 to obtain the desired product (1.8g, yield : 67%). 1 H NMR(CDC1 3 ) : δ 2.73(s, 3H), 2_97(s, 3H), 7.6 ~ 7.93(m, 1H), 15.73(s, 1H). EXAMPLE 26 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-(2,4-dichlorobenzylthio)-2- quinohnone (39) N-(4-Chloro-2-trifluoromethylphenyl)-« -[bis(2,4-dichloiObenzylthio) ylidene]-acetoacetamide (6.0g, 0.01 mol) was used, but the reaction was carried out as the above process of example 1 to obtain the desired product (2.4g, yield : 51%). l H NMR(CDC1 3 ) : δ 15.68(s, 1H), 8.57(m, 1H), 8.17(m, 1H), 7.67 ~ 7.03(m, 4H), 4.87(s, 2H), 2.97(s, 3H). EXAMPLE 27 : 3-Acetyl-8-chloro-4-methylsulfoxy-2-quinoIinone (91) 3-Acetyl-8-chloro-4-methylthio-2-quinolinone (26.7g, 0.1 mol)(3) was dissolved in 200ml of ethyl alcohol, and herein the solution of magnesium monoperoxyphthalate (29.1g, 0.1 mol) dissolved in 150ml of water was added dropwise at room temperature. After raising the reaction temperature to 50 _ , the reacting solution was maintained for 2hr, and then ethyl alcohol was evaporated and 500ml water was added. The obtained solid was filtered and recrystallized in 100m/ of ethyl alcohol to afford the desired product(23.2g, yield : 82%). 1 H NMR(CDC1 3 ) : δ 8.3 ~ 7.5(m, 3H), 3.1(s, 3H), 2.8(s, 3H). EXAMPLE 28 : 3-Acetyl-6-methoxy-4-methylsulfoxy-2-quinolinone (92) 3-Acetyl-6-methoxy-4-methylthio-2-quinolinone (2.6g, 0.01 mol)(5) was dissolved in 10ml of acetic acid, and the solution was stirred at δO . , and herein hydrogen peroxide (30% solution 2.83g, 0.025 mol) was added dropwise and stirred for30min at 80C After reacting under the above conditions, the solution was cooled and poured in 500g of ice water, and then the deposited solid was filtered and dried to obtain the desired product (2.3g, yield : 85%). 5 ' H NMR(CDC1 3 ) : δ 7.9 ~ 7.3(m, 3H), 3.9(s, 3H), 3.0(s, 3H), 2.8(s, 3H). EXAMPLE 29 : 3-Acetyl-5,8-dichloro-4-methylsulfoxy-2-quinolinone (93) 3-Acetyl-5,8-dic__loro-4-methylthio-2-quinoUnone (3.0g, 0.01 mol)(4) was used, but the reaction was carried out as the above process of example 27 to obtain the o desired product (2.4g, yield : 78%). 1 H NMR(CDC1 3 ) : δ 8.0 ~ 7.0(m, 2H), 3.1(s, 3H), 2.75(s, 3H). EXAMPLE 30 : 3-Acetyl-8-fluoro-4-methylsulfoxy-2-quinoUnone (97) 3-Acetyl-8-fluoro-4-methylthio-2-quinolinone (2.5g, 0.01 mol)(8) was used, but the reaction was carried out as the above process of example 27 to obtain the desired product (2.0g, yield : 79%). 1 H NMR(CDC1 3 ) : δ 8.3 ~ 7(m, 4H), 3.05(s, 3H), 2.82(s, 3H). EXAMPLE 31 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-methylsulfoxy-2- quinolinone (98) 3-Acetyl-6-chloro-8-trifluoromethyl-4-methylthio-2-quinolinone (3.4g, 0.01 mol)(13) was used, but the reaction was carried out as the above process of example 27 to obtain the desired product (2.9g, yield : 85%). H NMR(CDC ) : £ 2.75(s, 3H), 3.0(s, 3H), 8.6(d, 1H), 8.0(d, 1H), 11.25(s, 1H). EXAMPLE 32 : 3-Acetyl-4-benzylsulfoxy-8-fluoro-2-quinolinone (100) 3-Acetyl-4-benzylthio-8-fluoro-2-quinolinone (3.2g, 0.01 mol)(15) was used, but the reaction was carried out as the above process of example 27 to obtain the desired product (2.9g, yield : 87%). 1 H NMR(CDC1 3 ) : 2.86(s, 3H), 4.37(s, 2H), 7.13 ~ 7.47(m, 8H), 8.16(s, 1H). EXAMPLE 33 : 3-Acetyl-8-trifluoromethyl-4-methylsulfoxy-2-quinolinone (102) 3-Acetyl-8-trifluoromethyl-4-methylthio-2-quinolinone (3.0 g, 0.01 mol)(29 was used, but the reaction was carried out as the above process of example 27 t obtain the desired product (2.5g, yield : 82%). 1 H NMR(CDC1 3 ) : δ 2.87(s, 3H), 3.03(s, 3H), 7.52 ~ 8.78(m, 3H), 11.25(s, 1H). EXAMPLE 34 : 3-Acetyl-8-cyano-4-methylsulfoxy-2-quinolinone (104) 3-Acetyl-8-cyano-4-methylthio-2-quinolinone (2.6g, 0.01 mol)(29) was used, but the reaction was carried out as the above process of example 27 to obtain the desired product (1.8g, yield : 68%). 1 H NMR(GDC1 3 ) : δ 2.67(s, 3H), 7.6 ~ 8.67(m, 4H). EXAMPLE 35 : 3-Acetyl-5,8-dic_ oro-4-(p-chlorophenyl)thio-2-quinolinone (182) 3-Acetyl-5,8-dichloro-4-methylsulfoxy-2-quinolinone (3.2g, 0.01 mol)(93) and p-chlorothiophenol(1.73g, 0.012 mol) were stirred at 200'C , heated for 30min, slowly cooled to 100 * , and dissolved in 15 ml of toluene. After cooling to room temperature, the deposited crystal was filtered and dried to obtain the desired product (3.3g, yield : 83%). 1 H NMR(CDC1 3 ) : δ 1.2 8.3(m, 6H), 3.00(s, 3H). EXAMPLE 36 : 3-Acetyl-5,8-dichloro-4-(p-chlorophenyl)sulfoxy-2-quinolinone (184) 3-Acetyl-5,8-dichloro-4-(p-chlorophenyl)thio-2-quinolinone (lg, 0.0025 mol) (182) was dissolved in the mixture of 5ml of acetic acid and hydrogen peroxide (30% solution 0.57g, 0.005 mol), and stirred for 30 min at 100 * . The solution was poured in 50g of ice water, and then the deposited solid was filtered and dried to obtain the desired product (0.8g, yield : 73%). 1 H NMR( DMSOd 6 - CDC1 3 ) : δ 7.2 ~ 8.3(m, 6H), 3.05(s, 3H). 5 EXAMPLE 37 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-(2-phenylethylamino)-2- quinolinone (223) 3- Acetyl-6-chloro-8-trif luoromethyl-4-methylsul foxy-2-quinolinone (3.5g , 0.01 mol) and 2-phenylethylamine(1.21g, 0.01 mol) were dissolved, refluxed in 50ml o of tetrahydrofuran under heating for 4hr. After reacting, the solvent was evaporated under the reduced pressure, and then the obtained solid was dissolved in 10ml of ethylacetate under heating. The solution was recrystallized with adding 30ml of hexane to obtain the desired product (2.57g, yield : 73%). Η NMR (CDC J ) : δ 11.78(brs, 1H), 8.47(d, J=2.0, 1H), 7.75(d, J=2.0, 1H), 7.75(brs, 1H), 7.33(s, 5H), 3.55(m, 2H), 3.08(m, 2H), 2.7(s, 3H). EXAMPLE 38 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-isopropylamino-2- quinolinone (224) 3- Acetyl-6-chloro-8-trif luoromethyl-4-methylsul foxy-2-quinolinone (3.5g , 0.01 mol)(13) and isopropylamine (0.6g, 0.01 mol) were used, but thereaction was carried out as the above process of example 37 to obtain the desired product (2.52g, yield : 73%). Η NMR (CDC1 3 ) : δ 11.7(s, 1H), 8.58(m, 1H), 7.87(m, 1H), 3.77(m,J =6.5, 1H), 2.93(s, 3H), 1.47(d, J=6.5, 6H). EXAMPLE 39 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-cyclopentylamino-2- quinolinone (227) 3-Acetyl-6-chloro-8-trif luoromethyl-4-methylsul foxy-2-quinolinone (3.5g , 0.01 mol) and cyclopentylamine (0.86g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.5g, yield : 67%). Η NMR (CDCI 3 ) : δ 11.8(brs, 1H), 8.47(m, 1H), 7.83(brs, 1H), 7.77(m, 1H), 3.85(brs, 1H), 2.73(s, 3H), 2.47 ~ 1.38(m, 8H). EXAMPLE 40 : 8-Chloro-3-propionyl-4-isopropylamino-2-quinolinone (229) 8-C__loro-4-methylsulfoxy-3-propionyl-2-quinolinone (2.97 g, 0.01 mol) and isopropylamine (0.6g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.93g, yield : 71%). Η NMR (CDC1 3 ) : £ 11.78(br, 1H), 8.4 ~ 6.97(m, 4H), 3.87(m,J=7.0, 1H), 3.27(q, J=8.0, 2H), 1.65(d, J=7.0, 6H), 1.17(t, J=8.0, 3H). EXAMPLE 41 : 3-Acetyl-8-methyl-4-isopropylamino-2-quinohnone (230) 3-Acetyl-8-methyl-4-methylsulfoxy-2-quinolinone (2.63g, 0.01 mol) and isopropylamine (0.6g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.59g, yield : 68%). Η NMR (DMSO-d 6 ) : δ 11.5(br. d, 1H), 8.33 ~ 7.23(m, 4H), 3.8(m, J=7.0, 1H), 2.77(s, 3H), 2.4(s, 3H), 1.45(d, J=7.0,6H) EXAMPLE 42 : 3-AcetyI-6-C-_Ioro-8-trifluoromethyl-4-(p-fluorophenethyl amino)-2-quinolinone (227) 3-Acetyl-6-chloro-8-trifluoromethyl-4-methylsulfoxy-2-quinolinone (3.5g, 0.01 mol), p-fluorophenethylaminehydrochloride(1.76g, 0.01 -mol) and triethylamine (l.lg, 0.01 mol) were used as the above process of example 37, and the solvent was evaporated under the reduced pressure. The residue was dissolved in 50ml of ethylacetate, washed with 50ml of water, dried with magnessium sulfate, and then the solvent was evaporated. The obtained solid was dissolved in 10 ml of ethyl acetate, and crystallized by adding 30ml of hexane to afford the desired product (2.25g, yield : 53%). Η NMR (CDC1 3 ) : δ 2.7(s, 3H), 2.97 ~ 3.16(t, J=6.4, 2H), 3.47 ~ 3.77(m, 2H), 6.93 ~ 8.47(m, 7H), 11.73(s, 1H). EXAMPLE 43 : 3-Acetyl-8-fluoro-4-(l-methoxy-2-propylamino)-2 -quinolinone (249) 3-Acetyl-8-fluoro-4-methylsulfoxy-2-quinolinone (2.67g, 0.01 mol) and 1 - methoxy-2-propylamine(0.88g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.53g, yield : 87%). Η NMR (CDC1 3 ) : δ 1.5(d, 3H), 2.8(s, 3H), 3.7 ~ 3.9(m, 3H), 3.6(s, 3H), 7.2 ~ 8.3(m, 4H). EXAMPLE 44 : 3-Acetyl-6-chloro-8-trifluoromethyl-4-ethylamino-2-quinolinone (251) 3-Acetyl-6-chloro-8-trif luoromethyl-4-methylsulfoxy-2-quinohnone (3.5g , 0.01 mol) and ethylamine(70 wt % solution ; 0.65g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.52g, yield : 76%). Η NMR (CDC1 3 ) : δ 1.37 ~ 1.6(t, J=8, 3H), 2.73(s, 3H), 3.23 ~ 3.67(m, 2H), 7.77 ~ 8.47(m, 3H), 11.57(s, 1H). EXAMPLE 45 : 3-Acetyl-8-fluoro-4-(2-methylcyclohexylamino)-2-quinolinone (256) 3-Acetyl-8-fluoro-4-methylsulfoxy-2-quinolinone (2.67 r g, 0.01 mol) and 2 methylcyclohexylamine(1.13g, 0.01 mol) were used, but the reaction was carried ou as the above process of example 37 to obtain the desired product (2.1g, yield : 66%). 1 H NMR (CDC1 3 ) : δ 1.0 - 1.5(m, 12H), 2.6(s, 3H), 3.9(m, 1H), 7.1 - 8.4(m, 3H). EXAMPLE 46 : 3-Acetyl-8-trifluoromethyl-4-(ff -methylbenzylamino)-2- quinolinone (260) 3-Acetyl-8-trifluoromethyl-4-methylsulfoxy-2-quinolinone (3.17g, 0.01 mol) and a -methylbenzylamine (1.21g, 0.01 mol) were used, but the reaction was carried out as the aboveprocess of example 37 to obtain the desired product (2.43g, yield : 65%). Η NMR (CDCI 3 ) : δ 1.63 - 1.83 (d, J=7, 3H), 2.8(s, 3H), 4.57 - 4.77(m, 1H), 7.23 - 8.6(m, 9H), 12.2(s, 1H). EXAMPLE 47 : 3-Acetyl-8-chloro-4-(p-chlorobenzylamino)-5-nitro-2- quinolinone (308) 3-Acetyl-8-chloro-4-methylsulfoxy-5-nitro-2-quinolinone (3.28g, 0.01 mol) and p-chlorobenzylamine (1.42g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.32g, yield : 57%). Η NMR (DMSO-d 6 ) : δ 11.9(m, 1H), 8.43(brs, 1H), 7.8(d, J=9.0, 1H), 7.5(s, 4H), 7.3(d, J=9.0, 1H), 4.9(d, J=6.0, 2H), 2.7(s, 3H) EXAMPLE 48 : 3-Acetyl-6,8-dichloro-4-(2-methylchclohexylamino)-2- quinolinone (311) 3-Acetyl-6,8-dichloro-4-methylsulfoxy-2-quinolinone (3.18g, 0.01 mol) an 2-methylcyclohexylamine (1.13g, 0.01 mol) were used, but the reaction was carried out as above process of example 37 to obtain the desired product (2.68g, yield : 73%). 5 Η NMR (CDC1 3 ) : δ 12.0(m, 1H), 8.2(d, J=2.0, 1H), 7.9(brs, 1H), 7.6(d, J=2.0, 1H), 3.0(m, 1H), 2.8(s, 3H), 1.0 - 2.5(m, 9H), 1.0 - 1.2(m, 3H) EXAMPLE 49 : 3-Acetyl-7-t-butyl-4-cyclobutyl_tmino-2-qιinolinone (377) o 3-Acetyl-7-t-butyl-4-methylsulfoxy-2-methylsulfoxy-2-quinohnone (3.05g, 0.01 mol) and cyclobutylamine (0.71g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.6g, yield : 83%). Η NMR (GDC1 3 ) : δ 11.4(m, 1H), 8.3 ~ 8.4(d, 1H), 7.2 - 7.7(m, 2H), 2.9(s, 3H), 1.5 - 2.9(m, 4H), 1.2(s, 9H), 0.9 - l.l(m, 2H) EXAMPLE 50 : 3-Acetyl-8-ethyl-4-cyclopentylamino-2-quinolinone (400) 3-Acetyl-8-ethyI-4-methylsulfoxy-2-quinolinone (2.77 g, 0.01 mol) and cyclopentylamine (0.86g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.15g, yield : 72%). Η NMR (CDC1 3 ) : δ 11.6(m, 1H), 8.1(d, J=6.0, 1H), 7.4 - 7.1(m, 3H), 3.8(m, 1H), 2.8(s, 3H), 2.7(m, 2H), 2.1 ~ 1.5(m, 8H), 1.4(t, J=6.0, 3H). EXAMPLE 51 : 3-Acetyl-6-chloro-8-methyl-4-(p-fluorophenethylamino)-2- quinohnone (420) 3-Acetyl-6-chloro-8-methyl-4-methylsulfoxy-2-quinolinone (2.98g, 0.01 mol) and p-fluorophenethylamine hydrochloride (1.76g, 0.01 mol) were used, but the reaction was carried out as the above process of example 42 to obtain the desired product (2.9g, yield : 71%). 'H NMR (DMSO-d 6 ) : δ 11.5(m, 1H), 8.3(s, 1H), 7.9(s, 1H), 7.6 - 6.8(m, 5H), 3.77(m, 2H), 3.0(t, J=7.0, 2H), 2.6(s, 3H), 2.4(s, 3H) EXAMPLE 52 : 3-Acetyl-5,8-dichloro-4-(N-morpho_ino)-2-quinolinone (513) 3-Acetyl-5,8-dicUOTo-4-memylsιi-foxy-2-quinolinone (3.18g, 0.01 mol) and morpholine (0.87g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.56g, yield : 75%). Η NMR (DMSO-d 6 ) : δ 6.7 - 7.3(m, 3H), 2.9 - 3.3(m, 8H), 2.3(s, 3H) EXAMPLE 53 : 3-Acetyl-5,7-dimethyl-4-(<8 -methylphenethylamino))-2- quinolinone (533) 3-Acetyl-5,7-d-memyl-4-methylsulfoxy-2-quinolinone (2.77g, 0.01 mol) and β -methylphenethylamine (1.35g, 0.01 mol) were used, but the reaction was cairied out as the above process of example 37 to obtain the desired product (2.96g, yield : 85%). Η NMR (DMSO-d 6 ) : δ 11.6(m, 1H), 7.2(s, 5H), 6.7 ~ 7.1(d, 2H), 3.5(m, 2H), 3.2(m, 1H), 2.7(s, 3H), 2.6(s, 3H), 2.2(s, 3H), 1.3(d, 3H) EXAMPLE 54 : 3-Acetyl-4-sec-butylamino-8-isopropyl-2-quinolinone (543) 3-Acetyl-4-methylsulfoxy-8-isopropyl-2-quinolinone (2.91g, 0.01 mol) and sec-butylamine (0.73g, 0.01 mol) were used, but the reaction was cairied out as the above process of example 37 to obtain the desired product (2.7g, yield : 90%). Η NMR (CDC1 3 ) : δ 11.6(m, 1H), 8.2(d, J=8.0, 1H), 7.7 - 7.1(m, 3H), 3.5(m, 1H), 2.9(m, 1H), 2.8(s, 3H), 1.7(m, 2H), 1.4(m, 9H), l.l(t, J=6.0, 3H) EXAMPLE 55 : 3-Acetyl-4-(/8 -methylphenethylamino)-8-phenyl-2-quinolinone (565) 3-Acetyl-4-methylsulfoxy-8-phenyl-2-quinohnone (3.25g, 0.01 mol) and β - methylphenethylamine (1.35g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (3.29g, yield : 83%). Η NMR (DMSO-d 6 ) : δ 11.3(m, 1H), 8.3(brs, 1H), 8.3 - 8.0(m, 1H), 7.8 - 6.9(m, 12H), 3.3(m, 2H), 3.03(m, 1H), 2.6(s, 3H), 1.23(d, J=7.0, 3H) EXAMPLE 56 : 3-Acetyl-4-allylaminc-8-propyl-2-quinohnone (603) 3-Acetyl-4-allyl_tmmo-8-propyl-2-quinolinone (2.91g, 0.01 mol) and allylamine (0.57g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.3 lg, yield : 75%). Η NMR (CDC1 3 ) : δ 11.6(m, 1H), 8.1(d, J= 8.0, 1H), 7.7 ~ 7.1(m, 3H), 6.0 - 5.3(m, 3H), 4.1(brs, 2H), 2.8(s, 3H), 2.6(t, J=7.0, 2H), 1.5(m, 2H), 1.0(t, J= 6.0, 3H) EXAMPLE 57 : 3-Acetyl-4-allylamino-8-chloro-6-methyl-2-quinolinone (611) 3-Acetyl-8-chloro-6-methyl-4-methylsulfoxy-2-quinolinone (2.97 g, 0.01 mol) and allylamine (0.57g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.38g, yield : 82%). Η NMR (DMSO-d 6 ) : δ 11.6(m, 1H), 8.2(s, 1H), 7.4 ~ 7.7(d, 2H), 5.0 - 6.1(m, 3H), 3.1(t, 2H), 2.5 (s, 3H), 2.2(s, 3H) EXAMPLE 58 : 3-Acetyl-4-allylamino-5-chloro-6-methyl-2-quinolinone (632) 3-Acetyl-5-chloro-6-methyl-4-methylsulfoxy-2-quinolinone (2.69 g, 0.01 mol) and allylamine (0.57g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.23g, yield : 77%). Η NMR (CDC1 3 ) : δ 11.4(m, 1H), 7.1 - 7.6(m, 3H), 5.1 - 6.2(m, 3H), 4.0 - 4.2(m, 2H), 2.6(s, 3H), 2.4(s, 3H) EXAMPLE 59 : 3-Acetyl-8-chloro-4-(p-chlorophenethylamino-5-methyl-2- quinolinone (656) 3-Acetyl-8-chloro-5-methyl-4-methylsulfoxy-2-quinolinone (2.97 g, 0.01 mol) and p-chlorophenethylamine (1.56g, 0.01 mol) were used, but the reaction was cairied out as the above process of example 37 to obtain the desired product (3.1 Ig, yield : 80%). Η NMR (DMSO-d 6 ) : δ 11.6(m, 1H), 8.7(s, 1H), 7.7(s, 4H), 7.1 - 7.9(m, 2H) , 3.9(q, 2H), 3.2(t, 2H), 2.9(s, 3H), 2.7(s, 3H). EXAMPLE 60 : 3-Acttyl-4-isoamylamino-6-fluoro-8-chloro-2-quino_inone (673) 3-Acetyl-8-chloro-6-fluoro-4-methylsulfoxy-2-quinolinone (3.02g, 0.01 mol) and isoamylamine (0.87g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.79g, yield : 86%). Η NMR (CDC1 3 ) : δ 11.6(m, 1H), 8.0 - 7.8(m, 2H), 7.4(dd, J=8.0, 2.0, 1H), 3.4(m, 2H), 2.8(s, 3H), 1.7(m, 3H), 0.9(d, J=6.0, 6H) EXAMPLE 61 : 3-Acetyl-4-isobutyIamino-5-trifluoromethyl-8-methoxy-2- quinolinone (682) 3-Acetyl-5-trifluoromehyl-8-methoxy-4-methylsulfoxy-2-quinolinone (3.47g, 0.01 mol) and isobutylamine (0.73g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.46g, yield : 69%). Η NMR (DMSO-d 6 ) : tf ll_l(m, 1H), 8.5(brs, 1H), 7.2 - 7.7(m, 2H), 4.2(s, 3H), 3.0 - 3.6(m, 2H), 2.6(s, 3H), 1.8 - 2.3(m,lH), l.Hd. J*=6.0. 6H) The fungicidal activities of 2-quinolinone derivatives(I) according to the present invention prepared by the above examples were tested by following Tests ; wherein all the test chemicals were readily dispersed in a standard formulation of acetone in water and surfactant Five ml of acetone containing 12.5 mg of the chemical was diluted in A5ml of Tween 20 solution (250 ppm). Fifty ml of this chemical solution was sprayed to plants on the turntable at the same time. All replicates of plants tested for fungicidal activity against 6 plant diseases were two pots, respectively. TEST 1 Fungicidal test for rice blast (RCB) Evaluation of activity against blast was done with rice plants in the 2 leaf stage, grown in 5cm pots with a foliage spray. Fifty ml test material was sprayed on the foliage. After the spray deposit had dried, the plants were inoculated with a suspension of conidia in water (1 x 10 6 spores/ 'ml) and placed in a dew chamber at 25 C for 24 hrs. For inoculum preparation, rice blast fungus was incubated on rice polish agar medium at 26X2 for 2 weeks, and then scratched airial mycelia with rubber and irradiated with near UV light for 2 days. The plants were then held in lighted growth chamber (26 ± 2C , 85%) for an additional 5 days, and rated on the disease severity. TEST 2 Fungicidal test for rice sheath blast (RSB) Rice plants in the 3 leaf stage were sprayed with 50 ml of chemical solution on the turntable. One day after drying, treated plants were inoculated by injecting inoculum, incubated in wheat bran medium at 25 C for 7 days, macerated into the mixer at the base of the rice plants. Those were moved to a lighted dew chamber at 28 C and then held for 5 days. The disease severity of each pot was examined and compared to the standard rating diagram. TEST 3 Fungicidal test for cucumber gray mold (CGM) Cucumber plants grown in the first leaf stage were sprayed with 50ml of chemical solution while those were rotated on the truntable. After the spray deposit had dried for one day, the treated foliage of cucumber was inoculated with conidia ( 1 x 10 6 spores/raZ) of B. dnerea incubated on potato dextrose agar medium at 25 C for 15 days by leaf spray all four sides of plants until just before runoff and then placed in 20 2 dew chamber for 4 - 5 days. The disease rating was made by ex-tmining the applied plants and comparing the percent disease on a leaf to the standard rating diagram. TEST 4 Fungicidal test for tomato late blight (TLB) Tests were made onto tomato plants grown in 5cm polyvinyl pots for 14 days by leaf spray. The foliage is sprayed to run off with a test chemical while the plan t rotated on a turntable. After the spray deposit dried for one day, the treated plants were inoculated by spraying then with a suspension of zoosporangia (1 x 10 5 zoosporangia/πzZ) incubated on V-8 juice agar medium at 20C for 2 weeks and then placed in a dew chamber at 18 * C for 48 hrs. Four days after inoculation, disease ratings were made on a investigation of the disease severity. TEST 5 Fungicidal test for wheat leaf rust (WLR) Tests were made on wheats (cultivar : Chokwang) grown in polyvinyl pots (diameter ; 5cm) for 7 days by foliage spray. The first leaf was sprayed while plants were rotating on a turntable with 50 mZ of a chemical solution. After the spray deposit dried, plants were dusted with a uredospores colonied on the second leaf of wheat and placed in a moist chamber at 20 _ for 24 hours. One day after inoculation, plant were moved to the plant growth chamber (20 2 , 70% RH) for inducing the disease. The fungicidal effect of the applied chemicals was investigated on the disease severity of wheats after 10 days. TEST 6 Fungicidal test for barley powdery mildew (BPM) The barley powdery mildew is an obligately parasitic fungus that must be transferred directly from infected plants to healthy plants in a relatively dry environment. The host plants (cultivar ; Allbori) sowed in polyvinyl pot(diameter ; 5cm) were grown in a greenhouse for 7 days. Healthy young bailey with fully expanded primary leaf was spray with a suspension of a test material. One day after drying, the applied plants were dusted with conidia of Erysiphe gramims formed on the primary leaf of barley. The inoculated plants were placed in a plant growth chamber at 22 ~ 24C and then induced the powdery mildew. The disease severity was rated after 7 day inoculation. Fungicidal activity of test chemical against the above 6 plant diseases was indicated with control value calculated by below formula to list the result as below Table 4. ( Percent of disease area in treatment 1 - x 100 _ Percent of disease area in untreated control J Table 4 Fungicidal effects for 2-quinolinone As the result of the above Table 4, the compounds according to the present invention have a high protective effect against CGM and TLB, and also RCB. The insecticidal activity of the compounds of the formula(I) according to the present invention was tested as following Tests 7 - 10. The Primary Screening(PRI) is designed to detect initial pest control activity of experimental compounds. The types of activity assayed are acute toxicity, and growth disruption. The bioassays are designed to detect contact and ingestion activity. The stage tested are as follows : adult brown planthopper(BPH), green peach aphid(GPA), and two-spotted spider mite(TSSM), and 3rd instar diamond- back moth(DBM). All experimental compounds are formulated in a 10 : 90 (acetone : water), Triton X-100 lOOppm solution at a single, unreplicated rate of 500 ppm. Formulated compounds are applied to the test species with the individual application methods respectively. TEST 7 Insecticidal test for brown plant hopper (BPH) Root parts of six rice seddlings (cultivar : Dongjin ; 5-6cm in length ; 5-10 day old) are rolled with cotton wool pads and rice seedhngs are put into the glass tes t tubes(p 3 x 15cm) containing 2ml water. Three to five day-old adult BPH (20 individuals) are collected from rearing cages by an aspirator, and placed into test tubes. Test chemicals are dissolved in 5ml acetone(100%), and formulated to the proper concentration in Triton X-100 (lOOppm), then sprayed onto the BPH directly . The test tubes are covered with nylon cloth and held in an incubator at 25 C . Insect mortalities are recorded at 24 and 48 hours after treatment. TEST 8 Insecticidal test for green peach aphid (GPA) Excised tobacco leaf disks (5.5cm in diameter) are dipped into the prepared test chemical solutions (30sec) and taken out. After drying (30min), leaf disks are placed in the pettidishes (φ 5.5 x 2cm) and apterous female adult GPAs (20 individuals) are enclosed. All petridishes are covered and held in an incubator at 25 C . Insect mortalities are recorded at 24 and 48 hours after treatment. TEST 9 Insecticidal test for two-spotted spider mite(TSSM) Excised kidney bean leaf disks (2.5cm in diameter) are placed on water saturated cotton wool pads fitted into pettidishes (f 5.5 x 2cm). Female adult TSSMs (30 individuals) are placed on leaf disks, and prepared test chemicals are sprayed. The pettidishes are covered and held in an incubator at 25 . Mite mortalities are recorded at 24 and 48 hours after treatment. TEST 10 Insecticidal test for diamond-back moth(DBM) Test chemicals are dissolved in 5ml acetone (100%), then formulated to the proper concentration in Triton X-100 (100 ppm). Excised cabbage leaf disks(5cm in diameter) are dipped into the solution (30sec) and taken out After drying (30min), leaf disks are placed in the pettidishes ( 5 x 1cm) and 3rd instar DBM larvae (10 individuals) are enclosed All petridshes are covered and held in an incubator at 25 X . Insect mortalities are recorded at 24 and 48 hours after treatment The mortality (%) of test chemical against the above plant diseases was calculated by the below formula to list the result as the following Table 5. No. of dead insects Mortality(%) = x 100 No. of treated insects Table 5. Insecticidal effects for 2-quinolinone (I) As the result of the above Table 5, the compounds of the foιmula(I) according to the present invention have selectively good activity against diamond-back moth and two-spotted spider mite.

Claims: WHAT IS CLAIMED IS : 1. 2-Quinolinone derivatives having the following general formula(I). wherein, Ri, R 2 , R 3 and R 4 are independently hydrogen, halogen, C j -C--. alkyl, branched C^- alkyl, C J -C J haloalkyl, C,-C_, aikoxy, C,-^ haloalkoxy, G . -C 3 alkylthio, C.-C 3 haloalkylthio, N0 2 , CN, aikoxy carbonyl, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzenesulfonyl, benzyl, substituted benzyl or morpholine ; R j is C,-C 5 alkyl, branched C j - alkyl, C,-C 6 cycloalkyl, phenyl, substituted phenyl, benzyl or phenylthio methyl ; and X is S(0)nR 6 , OR 9 or NAB ; wherein, n is 0 or 1 ; R^ is R 7 or Rg, and then R, is C, -C 6 alkyl, branched C 3 -C 6 alkyl, C, -C 3 haloalkyl, benzyl or substituted benzyl, and R 8 is phenyl, substituted phenyl, benzyl or substituted benzyl ; R g is C 2 -C 5 alkyl, branched G j -C 4 alkyl, C 5 -C 6 cycloalkyl, phenyl or substitoted phenyl ; A and B are combined together to form a saturated or unsaturated 5 or 6-membered cyclic ring or fused ring, optionally including a hetero atom selected from O or N, or optionally substituted with C,-C 3 alkyl or carbocyclic ring including N atom, or one of A and B is H and the other is R I0 or Z-Ar ; and then, R- 0 is saturated or unsaturated C j - ,, alkyl, branched C 3 -Cg alkyl or C 3 -C 6 cycloalkyl optionally including a hetero atom selected from O, S or N or optionally substitoted with -G j alkyl or alkoxycarbonyl, -G j haloalkyl, alkoxyalkyl, alkoxycarbonylalkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, pyrimidyl, or substituted pyrimidyl ; Z is C j -Q, alkyl chain , optionally containing cyclopropylene ring, or optionally substitoted with C J -G J alkyl, -G* aikoxy, - hydroxyalkyl or phenyl ; and Ar is C 3 -C 6 cycloalkyl, optionally including a nitrogen atom, or pyridyl, substituted pyridyl, or a phenyl group of the following fσrmulaQI) wherein, R π , R, 2 , R ]3 , R M and R B are independently H, halogen, - alkyl, branched C 3 -C 4 alkyl, Cj-C 4 haloalkyl, -G* aikoxy, phenyl, phenoxy, phenylthio, CN, N0 2 , NH 2 , or S0 2 NH 2 . 2. Fungicides including 2-quinoIinone derivatives having the following general formula(I) as an effective ingredient. wherein, R,, R 2 , R 3 , R 4 , R 5 and X are as defined in the above claim 1. 3. Insecticides including 2-quinolinone derivatives having the following general formula(I) as an effective ingredient. wherein, Rj, R^ R^ R 4 , R s and X are as defined in the above claim 1. A process for preparing the compounds of the following general formula(I) which comprises (a) condesing the compounds of following formula(Ib) with a thiol of the following formula(IV). HSR, ( IV ) wherein, R, , R., R 3 , R 4 , R 5 , R 7 and R g are as defined in the above claim 1 ; or (b) condensing the compounds of said formula(Ib) with an alcohol of the following formula( V) wherein, R g is as defined in the above claim 1 ; or (c) condesing the compound of said foτmula(Ib) with an amine of the following formula (VI) HNAB ( VI ) wherein, A and B are as defined in the above claim 1 ; or (d) oxidizing the compounds of said formula(I) wherein X is SR^ using a conventional procedure to provide compounds of said formula(I) wherein X is SOR 6 . wherein, Rj , R^ R 3 , R 4 , R^ and X are respectively as defined in the above claim 1. 5. A process for preparing 2-quinolinone derivatives of the following formula(Ia) by thermally cyclizing ketenedithioacetal a -anilide of the following formula(III). wherein, R,, R_,, R j , R 4 , R 5 and R-, are respectively as defined in the above claim 1.

Inventors: CHOI EUN BOK, KIM SUNG KEE, LEE GE HYEONG, LEE HYEON KYU, LEE YEON SOO, PAK CHWANG SIEK, YANG HUEI CHEOL, YON GYU HWAN, CHOI, EUN, BOK, KIM, SUNG, KEE, LEE, GE, HYEONG, LEE, HYEON, KYU, LEE, YEON, SOO, PAK, CHWANG, SIEK, YANG, HUEI, CHEOL, YON, GYU, HWAN
Applicants: KOREA RES INST CHEM TECH, KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY
Application year: 1992
Main classification: C07D215
IPC codes: A01N43, C07D215, C07D401, C07D413