CA2176567C - 1,3-oxazin-4-one derivatives, process and intermediates for their preparation and their use as herbicides - Google Patents

Abstract

This invention provides 1,3-oxazin-4-one derivatives represented by general formula (I): <IMG> in which R1 represents a phenyl group which may be substituted; R2 represents a hydrogen atom or a lower alkyl group; R3 represents a hydrogen atom, a lower alkyl group, an aralkyl group or a phenyl group which may be substituted; R4 and R5 each independently represent a lower alkyl group; and W represents an oxygen atom or a group represented by the formula -N(R6)- in which R6 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group. There are also provided herbicidal compositions containing the derivatives represented by general formula (II): <IMG> in which R4 and R5 each independently represent a lower alkyl group, and R10 represents a lower alkyl group or an aralkyl group, as intermediates for preparing them. The compounds according to the present invention exhibit strong herbicidal activities, and thus they are useful as active ingredients of agricultural chemicals.

Description

_1 _ DESCRIPTION
BACKGROUND OF THE INVENTION
1. Field of the invention This invention relates to novel 1,3-oxazin-4-one derivatives, herbicidal compositions containing~same, and novel intermediates for preparing same.

2. Description of the Related Art Certain types of 1,3-oxazin-4-one derivatives, such as 6-methyl-3-{1-methyl-1-phenylethyi)-5-phenyl-2,3-dihydro-4H-1,3-oxazin-4-one, and their herbicidal activities are disclosed in, for example, WO 093/15064.
However, the compounds described in the above-mentioned international publication differ from the compound of this invention since none of them have an acid amide substituent on the 3-position of the 1,3-oxazine ring. Further, the herbicidal activities and selective toxicities of the foregoing known compounds have been unsatisfactory.
SUMMARY OF THE INVENTION
The inventors of the present invention have earnestly studied a variety of 1,3-oxazin-4-one derivatives by synthesizing them and examining their physiological activities. As a result, the inventors found novel 1,3-oxazin-4-one derivatives which have remarkable selective herbicidal activity and exhibit excellent herbicidal activity to __ 2116561 various weeds at very small dosages without giving phytotoxicity to useful crops. Thus the present invention has been achieved. .
w According to the present invention, there are provided 9,3-oxazin-4-one derivatives represented by following general formula (1):
p Rd R5 Rt N~W~ Rs R2 of o c~~
in which R' represents a phenyl group which may be substituted; R2 represents a hydrogen atom or a lower alkyl, group; R3 represents a hydrogen atom, a lower alkyl group, an aralkyl group or a phenyl group which may be substituted; R4 and R5 each independently represent a lower alkyl group, W represents an oxygen atom or a group represented by the formula -N(Rfi)- in which Rs represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group.
According to the present invention, there also provided herbicidal compositions containing the above derivatives and N-methylene amino acid ester derivatives of intermediates for preparing same, which are represented by following formula (II):
Rd R5 ORIo HzC ~ N
O
(II) in which R4 and RS each independently represent a Power alkyl group;
R'° represents a lower alkyl group or ari aralkyl group.

DESCRIPTION OF THE PREFERRED EMBODIMENTS
The 1,3-oxazin-4-one derivatives and the intermediates for preparing same according to the present invention represented by the general formulae (I) and (ll), respectively, are described in detail below.
Atoms and groups of the compounds represented in the general formulae (I) and (I1) represented by R', R2, R3, R4, RS, Rs and R'° as defined above are exemplified as follows:
A phenyl group or a phenyl group which is substituted by a halogen atom, a hydroxy group, a lower alkyl group, a lower alkoxy group, a phenoxy group, a lower alkylthio group, a lower alkylsulfonyl group, a lower haloalkyl group, a lower haloalkoxy group, an alkoxycarbonyl group, an alkoxycarbonylaikoxy group, an acyl group, a cyano group or a vitro group. Examples of these groups include a phenyl group, a 2-fluorophenyl group, a 3-chlorophenyl group, a 3,5-dichloro-~I-hydroxyphenyl group, a 3-toluyl group, a 2,5-xylyl group, a 3-anisyl group, a 3-phenoxyphenyl group, a 3-methyithiophenyl group, a 2-chloro-5-(methylsulfonyl)phenyl group, a 3-(trifluoromethyl)phenyl group, a 3,5-bis(difluoromethoxy)phenyl group, a 3-methoxycarbonylphenyl group, a 3-(1-methoxycarbonyl)ethoxyphenyl group, a -3-nitrophenyl group, a 3-cyanophenyl group, a 3-acetylphenyl group, a 2-chloro-nitrophenyl group, a 3,5-dichlorophenyl group, a 2-fluoro-4-chforophenyl group, a 2,5-dichlorophenyl group, a 3,5-dichloro-4-methylphenyl group, etc.
Halogen Atom A fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.
Lower Alkyl ~ro m A lower alkyl group having one to six carbon atoms may be either straight chained or branched chained, such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tent-butyl group, a n-pentyl group, a neopentyl group, a tert-pentyl group or a hexyl group, etc.

~1?b5~1 Lower Alkenvl t~rouo A lower alkenyl group having two to five carbon atoms such as an allyl group, a 2-methyl-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 3-methyl-2-butenyl group, etc.
Lower Alkyd I ro m A lower alkynyl group having two to five carbon atoms such as a 2-propynyl group, a 1-methyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group, etc.
Lower Alkoxv C' A lower alkoxy group whose alkyl moiety has the same meanings as defined above, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a pentoxy group, etc.
ower A~[jsylthi r A lower alkyithio group whose alkyl moiety has the same meanings as defined above, such as a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, a pentylthio group, etc.
I ~w r AI ~rlsulfonvsro A lower alkylsulfonyl group whose alkyl moiety has the same meanings as defined above, such as a methylsulfonyl group, an ethylsulfonyl group, a propyisulfonyl group, an isopropylsulfonyl group, a butylsulfonyl group, a pentylsulfonyl group, etc.
Lower Haioalkvl Groom T
A lower haloalkyl group having one to four carbon atoms such as a bromomethyl group, a difluoromethyl group, a dichloromethyl group, a trifluoromethyl group, a 1-chloroethyl group, an 2-iodoethyl group, a 3-chloropropyl group, a 2-methyl-2-chloropropyl group, a 2,2,2-trifluoroethyl group, etc.
Lower Hatoalkoxv ~ros o A lower haloalkoxy group whose haloalkyl moiety has the same meanings as defined above, such as a trifluoromethoxy group, a difluoromethoxy group, a chlorodifluoromethoxy group, a 2-chloroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a 3-chloropropoxy group, etc.

2~?6551 An alkoxycarbonyl group having about two to eight carbon atoms such as a methoxycarbonyl group, an ethoxycarbonyl group, an isopropoxycarbonyl group, etc.
An aikoxycarbonylalkoxy group having about three to ten carbon atoms such as a methoxycarbonylmethoxy group, a 1-(methoxycarbonyl)ethoxy group, a 1-(ethoxycarbonyl)ethoxy group, a 1-methy!-3-(isopropoxycarbonyl)propyl group, etc.
An acyl group such as an acetyl groin, a propionyl group, a butyryl group, an isobutyryl group, etc.
An aralkyl group such as a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 1-methyl-1-phenylethyl group, a 1-methyl-2-phenylethyl group, a 1-ethyl-2-phenylethyl group, a 3-phenylpropyl group, etc.
Groups not specifically mentioned as examples of the above groups can be selected by optional combinations based on the above atoms and groups or according to common sense in this field.
Among the compounds represented by general formula (I) described above;
preferred groups of the compound include those compounds of general formula (I) in which R' is a phenyl group, a 2-fluorophenyl group, a 2-chlorophenyl group or a 2-methylphenyl group;
RZ is a hydrogen atom, a methyl group or an ethyl group;
R3 is a phenyl group; a phenyl group substituted at the 3-posifion by one substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group, a phenoxy group, a lower lialoalkyl group and a lower haloalkoxy group; or a phenyl group substituted at the 2- and 5-positions or 3- and 5-positions by two substituents selected from the group consisting of a halogen atom, a lower alkyl group, a ~~ 165~~.
-s-lower alkoxy group, a phenoxy group, a lower haloalkyl group or a lower haloalkoxy group;
R4 and RS are each independently a methyl group or a ethyl group;
W is a group represented by the formula -N-(Rs)-, in which the preferred group of R6 is a hydrogen atom or a methyl group.
A more preferred compound of general formula (I) is a compound represented by following general formula (1-'1 ):
~ H3C CH3 H Xr ~/ N~XZ
/ II
0 ~
H3c of X3 in which X', X2 and X3 each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a phenoxy group, a lower haloalkyl group or a lower haloalkoxy group.
Specific examples of the compound of genera! formula (I) above provided by the present invention will be shown in Tables '1 to 5 hereinbelow. In the Tables, abbreviations used have the following meanings.
Me: methyl group; Et: ethyl group;

Pr: n-propyl group;iPr: isopropyl group;

Bu: butyl group; iBu: isobutyl group;

sBu: sec-butyl tBu: tent-butyl group; group;

Hex: hexyl group; Ph: phenyl group;
Bn: benzyl group; 2-F-PH: 2 fluorophenyl; and no substituent.

Tabie 1 _N N W
0 ~ /' Y

Compd. X Y RZ R6 Melting No. Point ['Cj 1 - - Me H 134-137 2 ~ 2-F Me H i 29-131 -3 - 3-F ~ Me H 131-132.5 4 - 4-F Me H 49-51 - 2-CI Me H 146-148.5 6 - 3-CI Me H 140.5-144 7 - 4-CI Me H 86-88 8 - 2-Br Me H

- 3-Br Me H 105.5-153 - 4-Sr Me~ H

11 - 2-I Me H

12 - 3-I Me H 154-156 13 - 4-1 Me H

14 - 2-F, 3-F Me H 155-161 ~ 5 - 2-F, 4-F Me H 164-168.5 16 - 2-F, 5-F ~ Me H 115-120 17 - 2-F, 6-F Me H 176.5-178 18 - 3-F, 4-F Me H 129-130.5 19 - 3-F, 5-F Me H 177.5-178 . - 3-F, 4-F, 5-F Me H

21 . 2-F, 3-F, 4-F, 5-F, 6-F Me H 192-194 -22 - 2-Cl, 3-CI Me H 138-142 23 - 2-Cl, 4-CI Me H 144-149 ~~ ~b5b~
_$_ Table 1 (continued) Compel. X Y . RZ R; Melting No. Point ['Cj 24 - 2-Cl, 5-CI Me H 173-174 25 - 2-CI, 6-CI Me H

26 - 3-CI, 4-CI Me H 78-81 27 - 3-CI, 5-CI Me H 182-184.5 28 , 3-CI, 4-Ci, 5-C1 Me H 198.5-199.5 29 - 2-CI, 3-CI, 4-CI, 5-Ci, Me H

30 - 2-F, 4-CI ~ ~ Me H 126-131 ~

31 - 3-CI, 4-F Me H 168-169.5 32 - 3-Br, 5-Br Me H

33 - 3-CI, 5-F ~ Me H

34 - 2-Me Me H 169-171 35 - 3-Me Me H i 55-157 36 - 4-Me Me H 169-171 37 - 2-Me, 3-Me Me H

38 - 2-Me, 4-Me Me H

39 - 2-Me, ~-Me Me H 132-134 40 - 2-Me, 6-Me Me H 194-197 41 - 3-Me, 4-Me Me H

42 - 3-Me, 5-Me Me H 162-166 43 - 3-Me, 4-Me, 5-Me Me H

44 - 2-Me, 4-Me, 6-Me Me H

45 - 3-Me, 4-CI Me H

46 - 2-CI, 3-Me, 4-CI Me H 149-154 47 - 3-CI, 4-Me, 5-CI . Me H

48 - 2-Et ~ Me H

49 - 3-Et ~ Me H 118.5-120.5 50 - 4-Et Me H

51 - 2-Pr Me H

2) 76567 Table 1 (continued) Compel. X Y - R~ Rs Metting No. , Point (CJ

52 - 3-Pr Me H

63 - 4-Pr Me H

54 - 3-iPr ~ Me H '! 49-150 66 - 4-iPr Me H

_ 56 - 3-Bu Me H

57 - 4-Bu Me H

58 - 3-iBu ~ Me H

59 - 3-s8u Me H
' 60 - 4-tBu Me H

61 - 3-Hex Me H

62 - 4-Hex Me H

63 - 2-OMe Me H '! 62-164 64 - 3-OMe Me H 138.5-141 65 - 4-OMe Me H 154-i 55 66 - 2-OMe, 4-OMe Me H

67 - 2-OMe, 5-OMe Me H

68 - 3-OMe, 5-OMe Me H

69 - 3-.OMe, 4-OMe, 5-OMe Me H

70 - 3-CI, 4-OMe, 5-C! Me H

71 - 3-Br, 4-OMe, 5-Br Me H

72 - 3-CI, 4-OH, 5-CI Me H 170-172 73 - 3-Br, 4-OH, 5-Br Me H i 54-160.5 74 - 2-OEt Me H

75 - 3-OEt Me H

76 - 4-OEt - Me H

77 - 3-OPr Me H

7$ - 4-OPr Me H

79 - 3-OiPr Me H

Table1 (continued) R' R6 Merong Compel. X Y Point ('C]
No.

80 - 4-OiPr Me H

g1 - 3-OBu Me H

g2 - 2-OiBu Me H

g3 - 3-OsBu Me H

g4 - 4-Ot8u ~ Me H

g5 - 3-OHex Me H

gg - 4-OHex Me H

g7 - 2-OPh Me H

Me H 140-142.5 gg - 3-OPh gg - 4-OPh Me H

gp - 2-OPh, 5-OPh Me H

91 - 3-OPh, 5-OPh Me H

Me H 109.5-111 92 - 2-CF, Me H 140.5-142.0 g3 3-CF, Me H 74.5-78 g4 - 4-CF, Me H 177.5-178.5 95 - 2-CF,, 5-CF, Me H 172-175 gg - 3-CF,, 5-CF, 97 - 2-CHZCF, Me H

g8 - 3-CHZCF, Me H

99 - 4-CHZCF, Me H

100 - 2-CHzCF,, 5-CH~CF, Me H

101 - 3-CHZCF,, 5-CH~CF, Me H

Me H 134-140 102 - 2-OCHF, Me H 132.5-134 Me H 127-129 104 - 4-OCHFZ . ~

105 - 2-OCHF2, 5-OCHFz . Me H

106 - 3-OCHFz, 5-OCHFz Me H

107 - 3-Ct, 4-OCHF=, 5-CI Me H

Table 1 (continued) Compd. X Y - RZ R6 Metting No. Point ('Cj 108 - 3-Br, 4-OCHFZ, 5-Br Me H

109 - 2-OCF, ' Me H

110 - 3-OCF, Me H 146-150 111 - 4-OCF, Me H

112 - 2-OCF,, 5-OCF, Me H

i 13 - 3-OCF,, 5-OCF, ~ Me H

114 - 3-CI, 4-OCF,, 5-CI ~ Me H

' 115 - 3-Br, 4-OCF,, 5-Br Me H

116 - 2-OCHzCF, Me H
.

117 - 3-OCHZCF, Me H

118 - 4-OCHZCF, Me H

119 - 2-OCHzCF,, 5-OCH~CF, Me H

120 - 3-OCHZCF,, 5-OCH~CF, Me H

121 - 3-CI, 4-OCHZCF,, 5-CI Me H

122 - 2-CN Me H

123 - 3-CN Me H 70-72 124 - 4-CN Me H 84.5-87 125 - 2-CN, 5-CN Me H

126 - 3-CN, 5-CN Me H

127 - 2-NOZ Me H 172.5-174.5 128 - 3-NOZ Me H 165-168 129 - 4-N02 Me H 93.5-95 130 - 2-NOZ, 5-NOZ Me H

131 - 3-NO2, 5-NOZ Me H 110-115 132 - 2-NO~, 4-N02 - Me H

Table 1 (continued) Compel. X Y . R~ R6 MelSng No. Point ['C]

133 - 2-CF,, 4-NO~ Me H

134 - 3-CF,, 4-NO_ Me H

135 - 2-COOMe Me H 182-184 13fi - 3-COOMe Me H 170.5-171 137 - 4-COOMe Me H 132.5-134 138 - 3-COOEt Me H 1 fi7.5-171.5 139 - 3-COOtBu ~ Me H

140 - 2-OCHZCOOMe Me H

141 - 3-OCHzCOOMe Me H 120-123.5 942 - 4-OCH~COOMe Me H

143 - 2-OCH(Me)COOMe , Me H

144 - 3-OCH(Me)COOMe Me H 131.5-i 34 145 - 4-OCH(Me)COOMe Me H

14fi - 2-SMe Me H 14fi-150 147 - 3-SMe Me H 135-137.5 148 - 4-SMe Me H 1 fig-170 149 - 2-SOZMe Me H 120-125-150 - 3-SOzMe Me H

151 - 4-SOZMe Me~ H Measurement Impossible 152 - 3-OH Me H 193-19fi 153 - 4-OH Me H

154 - 2-COMB Me H

155 - 3-COMB Me H 151.5-154 15fi - 4-COMB Me H

157 - 3-COEt . Me H

_ 2~7~561 Table 1 (continued) Corr~pd. X Y . R' R6 Melting No. . Point [Cj 160 - 3-Br H H

162 - 3-F, 5-F : H H

163 - 2-Cl, 5-CI H H

164 - 3-Cl, 5-CI H H

165 - 3-Br, 5-Br H H .

166 - 3-Me ~ H H

167 - 2-Me, 5-Me H H

168 - 3-Me, 5-Me H H

169 - 3-Et H H

170 - 3-Pr H H

171 - 3-OMs H H

172 - 2-OMs, 5-OMs H H

173 - 3-OMe, 5-OMe H H

174 - 3-Cl, 4-OMe, 5-CI H H

175 - 3-OPh H H

177 - 2-CF3, 5-CF, H H

178 - 3-CF,, 5-CF, H H

180 - 2-OCHF2, 5-OCHFZ H H

181 - 3-OCHFz, 5-OCHFz H H

184 - 2-NO2, 5-NOz ~ H H

185 - 3-NOZ, 5-NOz H H

186 - - Et H

187 - 3-CI Et H 136-137 2'16561 Table 1 (continued) Compel. X Y R~ R6 Metting No. Point ['Cj 188 - 3-8r Et H

189 - 3-1 Et H

190 - 3-F, 5-F Et H

191 - 2-Ci, 5-Ci Et H

192 - 3-CI, 5-C) Et H

193 - 3-8r, 5-Br . Et H

194 - 3-Me ~ Et H

195 - 2-Me, 5-Me Et H

196 - 3-Me, 5-Me Et H

197 - 3-Et Et H

198 - 3-Pr Et H

199 - 3-OMe Et H

200 - 2-OMe, 5-OMs Et H

201 - 3-OMe, 5-OMe Et H

202 - 3-CI, 4-OMe, 5-Ci Et H

203 - 3-OPh Et H

204 - 3-CF, Et H 49-51 -205 - 2-CF3, 5-CF, Et H

206 - 3-CF,, 5-CF, Et H

207 - 3-OCHFz Et H

208 - 2-OCHF~, 5-OCHFZ Et H

209 - 3-OCHFZ, 5-OCHFz Et H

210 _ _ Pr H

211 - 3-Ci Pr H 117.5-119 212 - 3-CF, - Pr H

.213 - 3-CF, . Bu H

214 2-F - Me H 139.5-141 215 2-F 3-CI Me H 129-134 ._ ~ 2~Tb5b7 Table 1 (continued) Compel. X Y . RZ R6 Metting No. Point ['C) 21 fi 2-F 3-8r Me H

217 2-F 3-I Me H

218 2-F 3-F, 5-F Me H

219 2-F 2-CI, 5-Cl Me H

220 ~ 2-F 3-C1,~5-CI Me H 1fi8-169.5 221 2-F 3-Br, 5-Br Me H

222 2-F 3-Me ~ Me H

223 2-F 2-Me, 5-Me Me H
~

224 2-F 3-Me, 5-Me Me H

225 2-F 3-Et Me H
.

226 2-F 3-Pr Me H

227 2-F 3-OMe Me H

228 2-F 2-OMe, 5-OMe Me H

229 2-F 3-OMe, 5-OMe Me H

230 2-F 3-Cl, 4-OMe, 5-CI Me H

231 2-F 3-OPh Me H

232 2-F 3-CF, Me H -233 2-F 2-CF3, 5-CF, Me H

234 2-F 3-CF,, 5-CF, Me H

235 ~ 2-F 3-OCHF2 Me H

236 2-F 2-OCHF2, 5-OCHFZ Me H

237 2-F 3-OCHF~, 5-OCHFz Me H

238 2-F 3-CN Me H

239 2-F 3-NO~ Me H

240 2-F 2-NOZ, 5-N02 ~ Me H

241 2-F 3-NO~, 5-NO~ Me H

242 2-CI - Me H

243 2-CI 3-CI Me H

- ~~ 16561 Table 1 (continued) Compel. X Y . RZ Rs Matting No. Point ['C) 244 2-Cl 3-Br Me H

245 2-Cl 3-1 Me H

246 2-CI &F, 5-F Me H

247 2-CI 2-CI, 6-CI Me H

248 2-CI 3-CI, 5-CI Me H

249 2-CI 3-Br, 5-Br Me H

250 2-C1 3-Me Me H

251 2-CI 2-Me, 5-Me Me H

252 2-CI 3-Me, 5-Me Me H

253 2-CI 3-Et Me H

254 2-Cl 3-Pr Me H

255 2-CI 3-OMe Me H

256 2-CI 2-OMe, 5-OMe Me H

257 2-Cl 3-OMe, 5-OMe Me H

258 2-CI 3-CI, 4-OMe, 5-CI Me H

259 2-CI 3-OPh Me H

260 2-C) 3-CF, Me H

261 2-CI 2-CF,, 5-CF, Me H

262 2-CI 3-CF,, 5-CF, Me H

263 2-Cl 3-OCHFZ Me H

264 2-CI 2-OCHF2, 5-OCHFz Me H

265 2-CI 3-OCHFZ, 5-OCHFz Me H

266 2-Cl 3-CN Me H

267 2-CI 3-NOZ Me H

268 2-CI 2-NOz, 5-NOZ . Me H

269 2-CI 3-NOz, 5-NO~ Me H

270 2-Me - Me H

2' 15~5~7 Table 1 (continued) Compel. X Y _ R= R6 Melting No. Point {'C]

271 2-Me 3-CI Me H

272 2-Me 3-Br Me H

273 2-Me 3-I Me H

274 2-Me 3-F, 5-F Me H

275 2-Me 2-CI, 5-CI ' Me H

276 2-Me 3-CI, ~-C) Me H

277 2-Me 3-Br, 5-Br ~ Me H

278 2-Me 3-Me Me H

279 2-Me 2-Me, 5-Me Me H

280 2-Me 3-Me, 5-Me Me H

281 2-Me 3-E# Me H

282 2-Me 3-Pr Me H

283 2-Me 3-OMe Me H

284 2-tvte2-OMe, 5-OMe Me H

285 2-Me 3-OMe, 5-OMe Me H

286 2-Me 3-CI, 4-OMe, 5-CI Me H

287 2-Me 3-OPh Me H

288 2-Me 3-CF, Me H

289 2-Me 2-CF,, 5-CF3 ~ Me H

290 2-Me 3-CF3, 5-CF, Me H

291 2-Me 3-OCHFz Me H

292 2-Me 2-OCHF2, 5-OCHFi Me H

293 2-Me 3-OCHFz, 5-OCHFz Me H

294 2-Me 3-CN Me H

295 2-Me 3-NOZ . Me H

298 2-Me 2-NOZ, 5-NOz . Me H

297 2-Me 3-N02, 5-NOZ Me H

298 - - Me Me 9 86-9 87 2~ ?65~~' -,8 _ Table 'I (continued) Compel. X Y _ RZ Rs Melting No. Point (C) 299 . 3-CI Me Me -300 - 3-Br Me Me 301 - 2-CI, 5-Cl Me Me ~

302 - 3-CI, 5-CI Me Me 64-67 303 - 3-Me Me Me 304 - 2-Me, 5-Me ~ Me Me 305 - 3-Me, 5-Me ~ Me Me 306 - 3-Et Me Me 307 - 3-Pr Me Me 308 - 3-OMe Me Me 309 - 2-OMe, S-OMe Me Me 310 - 3-OMe, 5-OMe Me Me 311 - 3-OPh Me Me 312 - 3-CF3 Me Me 313 - 3-OCHF= Me Me 314 - 3-NOZ Me Me 315 - 2-NO2, 5-NOZ Me Me -316 - 3-NOz, 5-NOz Me Me 317 - Me Et 318 - 3-CI Me Et 319 - 2-CI, 5-Cl Me Et 320 - 3-CI, 5-CI Me Et 321 - 3-Me Me Et 322 - 2-Me, 5-Me Me Et 323 - 3-Me, 5-Me ~ Me Et 2~~65f~
_19_ Table 1 (continued) Compel. X Y R~ R6 Melting No. Point ['C) 324 - 3-Et Me Et 325 - - Me CHZCH=CHz 326 - 3-CI Me CHZCH=CHI

327 - 2-CI, 5-CI Me CH~CH=CHZ

328 - 3-CI, 5-Cl . Me CHzCH=CHz 329 - 3-Me Me CHZCH=CHZ

330 - 3-CF3 ~ Me CHzCH=CH2 331 - 3-OCHFZ Me CHzCH=CHz 332 - - Me CHIC=CH

333 - 3-C! Me CHIC=CH

334 - 2-CI, 5-C! Me CH2CaCH

335 - 3-CI, 5-CI ~ Me - CHzCaCH

336 - 3-Me Me CHIC=-CH

337 - 3-CF3 Me CHzC=CH

338 - 3-OCHF2 Me CH2C=CH

339 - 2-F, 3-F, 4-F Me H 169.5-i 72.5 340 - 2-F, 3-F, 5-F Me H

341 - 2-F, 3-F, 6-F Me H 148.5-151 342 - 2-F, 4-F, 5-F Me H 137.5-139.5 343 - 2-F, 4-F, 6-F Me H 177-179 344 - 2-F, 3-F, 4-F, 5-F Me H 121.5-124.5 345 - 2-F, 3-F, 4-F, 6-F Me H 146-148 346 - 2-F, 3-F, 5-F, 6-F Me H 135.5-137 347 - 2-Cl, 3-CI, 5-CI Me H

348 - 2-CI, 4-Cl, 5-CI Me H
~

349 - 2-CI, 3-CI, 4-CI, 5-CI Me H 176-177 , 350 - 2-F, 5-CI Me H 14i-144.5 351 - 2-F, 5-Br Me H

~1T6561 Table 1 (continued) Compel. X Y RZ R6 Melting No. Point ['Cj 352 ~ 2-F, 5-1 Me H
-353 - 2-F, 4-Br Me H 127-134 354 - 2-F, 3-F, 4-Br, 5-F, Me H 186-187 355 - 2-F, 3-Cl, 5-CI Me H

356 - 3-tBu, 5-t8u Me H 186.5-187.5 357 - 2-F, 5-Me ~ Me H
' 358 - 2-F, 5-Et ~ Me H

359 - 2-F, 5-iPr Me H

360 - 2-F, 5-tBu Me H

361 - 3-Br, 4-Me, 5-8r Me H 176.5-178.5 362 - 2-F, 3-CF3 Me H 126.5-128.5 363 - 2-F, 5-CF, ~ Me H 146.5-149 364 - 3-CF,, 4-F Me H 152-154 365 - 3-CF,, 4-CI Me H 153-155.5 366 - 2-F, 5-OH Me H

367 - 2-F, 5-OMe Me H

368 - 2-F, 5-OPh Me H

369 - 3-F, 5-OPh Me H 58-61 370 - 3-CI, 4-OH Me H 92-93.5 37i - 2-F, 4-CI, 5-Oil'r Me H 180-182.5 372 - 2-F, 5-OCHFz ~ Me H

373 - 3-F, 5-OCHFZ ~ Me H

374 - 2-F, 5-NOz Me H 148-150.5 375 - 3-F, 5-NOZ Me H

376 - 3-NO~, 4-F Me H 161.5-164 377 - 3-F, 5-CF, Me H

378 - 3-CI, 5-CF, Me H

379 - 3-F, 5-Me Me H

=2176567 Table 1 {continued) Compel. X Y RZ R6 Matting No. Point [CJ

380 - 3-F, 5-OCHFZ Me H

381 2-F 2-F, 5-C) Me H

382 2-F 2-F, 5-Br Me H

383 2-F 2-F, 5-1 Me H

384 2-F 2-F, 5-CI Me H
.

385 2-F 2-F, 3-CI, 5-CI Me H

386 . 2-F 2-F, 5-Me ~ Me H

387 2-F 2-F, 5-Et Me H

388 2-F 2-F, 5-iPr Me H

389 2-F 2-F, 5 t8u Me H

390 2-F 2-F, 3-CF, Me H

391 2-F 2-F, 5-CF, Me H

392 2-F 3-F, 5-CF, Me H

393 2-F 3-CF3, 4-CI Me H

394 2-F 2-F, 5-OH Me H

395 2-F 2-F, 5-OMe Me H

396 2-F 2-F, 5-OPh Me H

397 2-F 3-F, 5-OPh Me H

398 2-F 2-F, 5-OCHFZ Me H

399 2-F 3-F, 5-OCHF2 Me H

- = 2~ 76567 Table 2 0 Rd Rs H
Ph N~ N
I ~ o I

Compd. R' Rs Y Melting No. Point [C]

400 Me Et 401 Me Et 3-CI

402 ~Me Et 3-Br 403 Me Et 3-!

404 Me Et 3-F, 5-F

405 Me Et 2-CI, 5-CI

406 Me Et 3-CI, 5-Ci 407 Me Et 3-Br, 5-Sr .408 Me Et 3-Me 409 Me Et 2-Me, 5-Me.

410 Me Et 3-Me, 5-Me 411 Me Et 3-Et 412 Me Et 3-Pr 413 Me Et 3-OMe 414 Me Et 2-OMe, 5-OMe .

415 Me Et 3-OMe, 5-OMe 416 Me Et 3-CI, 4-OMe, 5-Cl 417 Me Et 3-OPh .418 Me Et 3-CF, 419 Me Et 2-CF,, 5-CF, 420 Me Et 3-CF,, 5-CF, 421 Me Et 3-OCHF2 422 Me Et 2-OCHFZ, 5-OCHF~

217b5b1 Table 2 (continued) Compel. R' RS . Y Melting No. Point ['C]

423 Me Et 3-OCHFZ, 5-OCHF=

424 Me Et 3-CN

425 Me Et 3-NOz 426 Me' Et 2-NOZ, 5-NOz 427 Me Et 3-NO~, 5-NOZ

428 Me iPr 429 Me iPr 3-Ci 430 Me iPr 2-CI, 5-Cl 431 Me iPr 3-Ci, 5-CI

432 Me iPr 3-Me 433 Me iPr 2-Me, 5-Me 434 Me iPr 3-Me, 5-Me .435 Me iBu 436 Me iBu 3-Cl 437 Me iBu 2-CI, 5-CI

438 Me iBu 3-CI, 5-CI

439 Me iBu 3-Me 440 Me i8u 2-Me, 5-Me 441 Me iBu 3-Ms, 5-Me 442 Et Et 443 Et Et 3-CI

444 Et Et 2-CI, 5-CI

445 Et Et 3-CI, 5-CI

446 Et Et 3-Me 447 Et Et 2-Me, 5-Me 448 Et Et 3-Me, 5-Me _ 2176567 Table 3 0 R4 Rs Ph N 0 J o t, Compel. R' Rs Y Melting No. Point [C]

500 Me Me 501 Me Me 3-CI

502 Me Me 3-Br 503 Me Me 3-I

504 Me Me 3-F, 5-F

505 Me Me 2-CI, 5-C!

506 Me Me 3-Cl, 5-CI Oily 507 Me Me 3-Br, 5-Sr 508 Me Me 3-Me 509 Me Me 2-Me, 5-Me 510 Me Me 3-Me, 5-Me 511 Me Me 3-Et 512 Me Me 3-Pr -513 Me Me 3-OMe 514 Me Me 2-OMe, 5-OMe 515 Me Me 3-OMe, 5-OMe 576 Me Me 3-CI, 4-OMe, 5-CI

517 Me Me 3-OPh 518 Me Me 3-CF, 519 Me Me 2-CF,, 5-CF, 520 Me Me 3-CF,, 5-CF, 521 Me Me 3-OCHF~

522 Me Me 2-OCHFz, 5-OCHFZ

523 Me Me 3-OCHF2, 5-OCHFz 21165b1 Table 3 {continued) Compel. R' R5 . Y Melting No. ~ Point [Cj 524 Me Me 3-CN

525 Me Me 3-NOZ

526 Me Me 2-NOz, S-NO~

527 Me Me 3-NOZ, 5-NOz 528 Me Et 529 Me Et 3-CI
' 530 Me Et 2-CI, 5-CI

531 Me Et 3-CI, 5-CI

532 Me Et 3-Me 533 Me Et 2-Me, 5-Me 534 . Me Et 3-Me, 5-Me 535 Me Et 3-Et 536 Me Et 3-OMe 537 Me Et 3-OPh 538 Me Et 3-CF3 539 Me Et 3-OCHF, 540 Me Et 3-NO~

541 Me iPr 542 Me iPr 3-CI

543 Me iPr 2-CI, 5-CI

544 Me iPr 3-CI, 5-Cl 545 Me iPr 3-Me 546 Me iPr 2-Me, 5-Me 547 Me iPr 3-Me, 5-Me 548 Me iBu 549 Me iBu 3-CI

550 Me iBu 2-CI, 5-CI

551 Me iBu 3-CI, 5-CI

-2fi-Table 3 (continued) Compel. R' Rs . Y Melting No. Point ('Cj 552 Me iBu 3-Me 553 Me i8u 2-Me, 5-Me 554 Me i8u 3-Me, 5-Me 555 Et Et 556 Et Et 3-CI

557 t Et 2-CI, 5-Cl 558 Et Et 3-CI, 5-CI

559 Et Et 3-Me 560 Et Et 2-Me, 5-Me 561 Et Et 3-Me, 5-Me - . = 2~765~1 Table 4 0 .Ra R5 Ph N W. R3 Compel. R' Rs W R' Melting No. Point jCJ

600 Me Me NH H 185.5-189 601 Me Me NH Me 602 Me Me NH Et 603 Me Me NH Pr 604 Me Me NH if'r 129-131.5 605 Me Me NH Bu 606 Me Me NH ii3u 118.5-121 607 Me Me NH sBu 608 Me Me NH tBu 145.5-147 609 Me Me NH Hex 610 Me Me NH 8n 611 Me Me NH CH(Me)Ph 612 Me Me NH C(Me)zPh 200-201.5 613 Me Me NH CHZCH2Ph 130-132 614 Me Me NH CHZCHZCHzPh 615 Me Et NH H

616 Me Et NH Me 617 Me Et NH Et 618 Me Et NH Bn 619 Me Et NH CH(Me)Ph 620 Me Et NH C(Me)2Ph 621 Me Et NH CHZCHzPh 622 Me iBu NH~ Bn 623 Me Me NMe H

Table 4 (continued) Compel. R' Rs W R' Meit;ng No. Point [~Cj 624 Me Me NMe Me 112-117 625 Me Me~ NMe Et 626 Me Me NMe Pr 627 Me Me NMe iPr 628 Me Me NMe Su 629 Me Me NMe Bn 630 Me Me NMe CH(Me)Ph 631 Me Me NMe C(Me)~Ph 632 Me Me NMe CHZCH~Ph 633 Me Me NMe CHZCHZCHZPh 634 Me Me O H 202-205 635 Me Me O Me , 67-69 636 Me Me O Et Oiiy 637 Me Me O Pr 638 Me Me O ii'r Oiiy 839 Me Me O Bu 649 Me Me O iBu 642 Me Me O sBu 643 Me Me O t8u 644 Me Me O Hex 645 Me Me O Bn OiiY

646 Me Me O CH(Me)Ph 647 Me Me O C(Me)ZPh 648 Me . Me O CHZCHzPh 649 Me Me O CHzCHzCH2Ph 650 Me Et O H 184-187 _ 216561 Table 4 (continued) Compd. R' Rs W R' Melting No. Point ['CJ

651 Me Et O Me ~i~Y

652 Me Et O Et 653 Me Et O Pr 654 Me Et O iPr 655 Me Et O Bu 656 Me Et O i8u 657 Me Et O Bn 658 Me Et O CH{Me)Ph 659 Me Et O C(Me)ZPh 660 Me Et O CHZCHzPh 661 Me iPr O H

682 Me iPr O Me 663 Me iPr O Et 664 Me ii'r O Pr 665 Me iPr O iPr 666 Me iPr O Bu 667 Me iPr O iBu 668 Me iPr O Bn 669 Me ii'r O CH(Me)Ph 670 Me iPr O C(Me)zPh 671 Me iBu O H

672 Me iBu O Me 673 Me iBu O Et 674 Me iBu O iPr 875 Me iSu O iBu 676 Me ii3u . O Bn _. 21 ?6~E7 Table 5 ~' Rs ~J o Compd. R' RZ W R' Melting No. Point ['Cj 680 2-F-Ph Me O H 182-183.5 681 2-F-Ph Me O Me 682 2-F-Ph Me O Et ' 683 2-F-Ph Me O Bn Oily 684 Ph Et O H 152.5-153.5 685 . Ph Et O Me 686 Ph Et O Et 687 Ph Et O 8n 99-100 688 Ph Pr O H 120-122 ~

689 Ph Pr O Et 690 Ph Pr O Bn 53-56 The compound according to the present invention may be manufactured using any methods known in the art. For example, the compound represented by general formula (I) may be manufactured using the following methods.
O Ra Rs R1 O . . RQ Rs Rt ORja O H2C~ ORio N
+ N~~ ~ O
~.CH3 O R
R O C H3 ( I I ) ( I-2 ) ( III ) ~1?6567 in which R', R2, R4 and RS are as defined in general formula {I) and R'° is as defined in general formula (11).
The compound of formula (I-2) can be obtained by reacting a compound of formula {il) with a compound of formula (III) in the presence or absence of an adequate solvent.
The reaction temperature can be arbitrarily determined so far as it ranges from 90°C to '160°C or to the boiling point of the solvent.
The solvent, if used,. is not particularly limited so tar as it is inert with starting materials under the conditions of Method A, but in view of the reaction temperature, it is preferably a solvent having a higher boiling point, such as toluene, xylene or mesitylene.
Although the reaction time varies depending upon the setting conditions, the reaction can usually be completed in 1 to 240 minutes.
Although the quantitative ratio of the compounds of formulae (Il) and (ill) is not particularly limited, the. compound of formula {lll) is usually 0.5 to 2 moles, preferably 0.9 to 1.1 moles, per 1 mole of the compound of formula (Il).
The products of formula.(I-2) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
The N-methylene amino acid ester derivative represented by general formufia (11) shown below and used in the above reaction as a starting material is a novel.compound, which is also included in the scope of the present invention.
R~ Rs ORj°
H2C=N
~II~

__ 2 ~ 165b1 in which R° and RS each independently represent a lower alkyl group, and R'° represents a lower alkyl group or an aralkyl group.
Among the compounds represented by general formula (11) described above, preferred groups of the compound include those compounds of general formula (il) in which R° and RS are each independently a methyl group or an ethyl group; and R'° is a methyl group, an ethyl group or a benzyl group.
Specific examples of.the compound of general formula (I1) above provided by the present invention are shown in Table 6 hereinbelow. in Table 6, the abbreviations used are the same as in the foregoing Tables.

__ - 2~ 7G~6~

Table 6 R~
OR1°
H2C=N
O
Compel. No. R' Rs R' 2-i Me Me Me 2-2 Me Me Et 2-3 Me Me ' Pr 2-4 Me Me iPr 2-5 Me Me Bu 2-6 Me Me iBu 2-7 Me Me si3u 2-8 Me Me. tBu 2-9 Me Me Hex 2-10 Me Me Bn 2-1.1 Me Me CH(Me)Ph 2-12 Me Me C(Me)ZPh 2-13 Me Me CH~CHZPh 2-14 Me Me CHzCHZCH2Ph 2-i 5 Me Et Me 2-16 Me Et Et 2-17 Me Et Pr 2-i 8 Me Et iPr 2-19 Me Et Bu 2-20 Me Et ~ iBu 2-21 Me Et ~ sBu 2-22 Me Et tBu 2-23 Me Et Hex 2~1b561 Table 6 (continued) Compd. No. R' Rs R' 2 24 Me Et Bn 2-25 Me Et CH(Me)Ph 2-26 Me Et C(Me)~Ph 2-27 Me Et CHZCHZPh 2-28 Me Et CHZCHzCHZPh 2-29 Me ~ iPr Me 2-30 Me iPr Et 2-31 Me iPr ~ iPr 2-32 Me ii'r Bu 2-33 Me iPr tBu 2-34 Me iPr 8n 2-35 Me iPr CH(Me)Ph 2-36 Me iPr C(Me)zPh 2-37 Me ii'r CH~CHzPh 2-38 Me iBu Me 2-39 Me i8u Et 2-40 Me iBu iPr 2-41 Me iSu Bu 2-42 Me iBu tBu 2-43 Me i8u Bn 2-44 Me iBu CH(Me)Ph 2-45 Me iBu C(Me),Ph 2-46 N1e iBu CH~CHzPh 2-47 Et Et Me 2-48 Et Et Et -2-49 Et Et Bn = 2' 1656' The compound of formula (II) may be manufactured using any method known in the art. For example, it may be manufactured using the following method.
R~ R5 R4 Rs Formalin HzN ~Ri° H =N oRio 1 z tII~)o (II)o in which R4 and RS are as defined in general formula (!) and R'° is as defined in general formula (11).
The compound of formula (II) can be obtained by reacting one of amino acid esters of formula (il') with formalin in the presence or absence of an adequate solvent.
The reaction temperature can be arbitrarily determined so tar as it ranges from about 0°C to 140°C.
The solvent, if used, is not particularly limited so far as it is inert with the materials under the conditions of this method, and preferred examples of the solvent include hydrocarbons such as toluene or xylene; ethers such as diethyl ether, diisopropyl ether or tetrahydrofuran.
Although the reaction time varies depending upon the conditions, the reaction can usually be completed in 1 hour to 1 day.
Although the quantitative ratio of the compounds of formula (II') and formalin is not particularly limited, formalin is usually 1 to 5 moles, preferably 1.1 to 2 moles, per 1 mole of the compound of formula (II').
The products of formula (11) can be isolated and purified from the reaction mixture using a known method, such as extraction, distillation, recrystallization or chromatography.

~~165~1 The amino acid esters of formula {il') used in the above reaction as a starting material can be obtained by known methods or methods similar thereto.
The compound of formula (II) often makes an equilibrium condition with trimers thereof around room temperature, and thus said compound may be present as a mixture of the compound itself, that is monomers and trimers thereof. In addition, the whole compound may be present in the form of a trimer depending upon the condition.
However, the monomer name of said compound will be used no matter what form it takes so as to avoid unnessecary complication.
The compound of formula (111) is another starting material for synthesizing the compound of forri~ula (I-2) and can be obtained by several methods, for example by the method described in Chem. Pharm. Bull., ~.1.{6), 1896-7901 (1983) or methods similar (hereto.
O R~ Rs . O
R~ R5 R ~ ORi° H20 R1 OH
R2 O~ O Alkali ~ ~ O
( I_2 ) R O
in which R', R2, R4 and RS are as defined in general formula (I) and R'° is as defined in general formula (II).
The compound of formula (I-3) can be obtained by hydrolyzing the compound of formula (I-2) with an alkali.
Examples of an alkali include a solution of sodium hydroxide or potassium hydroxide.

-The solvent, if used in addition to water, is not particularly limited so far as it is inert under the conditions of Method B, and preferred examples of the solvent include alcohols such as methanol.or ethanol; ethers such as tetrahydrofuran or dioxane.
The reaction temperature is preferably about from room temperature to 80°C.
The products of formula (I-3) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
p R~ Rs OBn ~ H2 ~N N OH
O O Metal catalyst 2 J O

(I-4) (I-3 ~
in which R', R2, R4 and RS are as defined in general formula (I) and the abbreviation of Bn means a benzyl group. -The compound of formula (I-3) can be obtained by hydrogenating the compound of formula (i-4) in the presence of a metal catalyst.
Most of the metal catalysts commonly used as a catalyst for promoting hydrogenation, such as palladium-carbon, rhodium-carbon or platinum black, can be used as a metal catalyst for this method.
The solvent used is not particularly limited so far as it is inert under the condition of Method C, and preferred examples of the solvent include alcohols such as methanol or ethanol; acetic acid esters such as ethyl acetate; and acetic acid.
This reaction may be completed under the following condifions; hydrogen _._ atmosphere; normal pressure; room temperature; reaction time of from 1 hour to 1 day, and it also may be promoted by applying heat and/or pressure.
The amount of the catalyst added can be arbitrarily determined according to the reaction rate.
The products of formula {)-3) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
O Rd Rs O R4 Rs N OH Ph3p R3(IV) H R~ N
J O CCy J o O Base R2 O -~I_3 ) CI) in which R', R2, R3, R4, RS and W are as defined in general formula (I).
The compound of formula (I) can be obtained by reacting the compound of formula (I-3) with carbon tetrachloride and triphenylphosphine followed .by treatment with the compound of formula (IV) in the presence of base.
The reaction temperature is preferably from room temperature to about 140°C or to the boiling point of the solvent for the first process above, and 0°C to about 60°C for the second process.
The solvent used is not particularly limited so far as it is inert under the conditions of Method D, and preferred examples of the solvent include halogenated hydrocarbon solvents such as carbon tetrachloride, chloroform or methylene chloride;
hydrocarbon solvents such as toluene, xylene or mesitylene; and ether solvents such as diethyl ether, tetrahydrofuran or dimethoxyethane.

Examples of a base include tertiary amines such as triethyl amine, diisopropylethylamine or pyridine; inorganic bases such as sodium hydroxide or sodium carbonate. If required, the base can also be applied as a water solution or as a salt formed with the compound.of formula (IV). Furthermore, when the compound (IV) is an amine, an excess of said compound of formula (IV) can also be used as a base.
The products of formula (I) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromafography.
R4 R5 . n ~ O R4 Rs Ri N~OH N.~N~N~.N R3-~'H R1 YV
I O (IV) N

(I_3) (I) in which R', R2, R4, RS and W are as defined in general formula (i).
The compound of formula (I) can be obtained by reacting the compound of formula (1-3) with carbonyldiimidazoie followed by treatment with the compound of formula (IV) or the salt thereof.
The reaction temperature is preferably from 0°C to about 60°C
for the first process above, and from room temperature to about 100°C or to the boiling point of the solvent for the second process.
The reaction time is usually from 0.5 to 24 hours.
The solvent used is not particularly limited so far as it is inert under the conditions of Method E, and the preferred examples of the solvent include halogenated hydrocarbon solvents such as carbon tetrachloride, chloroform or methylene chloride;
hydrocarbon solvents such as toluene, xylene or mesitylene; ether solvents such as ~~T6551 -.ao -diethyl ether, tetrahydrofuran or dimethoxyethane; ketone solvents such as acetone or methyl ethyl ketone; and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide or N, N-dimethylacetoamide.
The products of formula (I) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
R~ R$
Ri N OH R~~_z R O R4 R5 0 I (v) N''~ ~Rz, R2 of ~ R2 ~ J o ( ~-~ , Hase O
C x-$
in which R', R2, R4 and RS are as defined in formula (I); R"~ is a primary or secondary lower alkyl group or an aralkyl group; Z is a halogen atom, a p-toluensulfonyloxy group, a methyisulfonyloxy group, a trifluoromethylsuifonyloxy group or a group which can be a good leaving group by the nucleophilic reaction as represented by formula OS020R".
The compound of formula (1-5) can be obtained by reacting the compound of formula (I-3) with the compound of formula (V) in the presence of base.
The reaction temperature is preferably from room temperature to about 140°C or to the boiling point of the solvent.
The solvent used is not particularly limited so far as it is inert under the conditions of Method F, and preferred examples of the solvent include polar aprofic solvents such as N,N-dimefhylformamide, dimethylsulphoxide, acetonitrile or acetone; ether solvents such as tetrahydrofuran or dioxane; alcohols such as methanol or ethanol; and a mixfure of water and the above-mentioned solvents.
Examples of base include inorganic carbonates such as potassium carbonate, potassium bicarbonate, sodium carbonate or sodium bicarbonate; inorganic bases such as sodium hydroxide or potassium hydroxide; sodium methoxide; and sodium hydride.
The base can also be applied as a salt formed with the compound of formula (1-3), if required.
The product represented by general formula (I-5) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
O R4 R5 O R4.Rs R1 ~~~ \ Oxidizing agent R~
w J o ~ , l ~SRtz \ ~2 (~S, (I-7 ) SOZR
in which R', R2, R3, R4, RS and W are as defined in general formula (I), and R'2 is a lower alkyl group.
The compound represented by general formula (1-7) can be obtained by oxidizing the compound of formula (I-6) with an adequate oxidizing agent.
Examples of the oxidizing agent include hydrogen peroxide, m-chloroperbenzoic acid, sodium metaperiodate, peracetic acid and potassium permaganate.
The reaction temperature is preferably from 0°C to about 140°C
or to the boiling point of the solvent.
The solvent used is not particularly limited so far as it is inert under the conditions of Method G, and preferred examples of the solvent include halogenated hydrocarbon 2t1G561 solvents such as 1,2-dichloroethane, carbon tetrachloride, chloroform or methylene chloride; methanol; acetic acid; water; and the mixture thereof.
The product represented by general formula (1-7) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
p R4 Rs . O R4 Rs Rt3 R~s_z R1 N N~R3 (YZ) N~~~~Rs J o R ~ J o R O Base 2 O
( z-8 ) ( z_9) in which R', R2, R3, R4 and RS are as in formula (!); R'3 is a primary or secondary lower alkyl group, a lower aralkenyl group or a lower alkynyl group; Z is as defined in. general formula (V).
The compound of formula (I-9) can be obtained by reacting the compound of formula (1-8) with the compound of formula (Vl) in the presence of base.
The reaction temperature is preferably from room temperature to about 140°C or to the boiling point of the solvent.
The solvent used is not particularly limited so far as it is inert under the conditions of Method H, and preferred examples of the solvent include polar aprotic solvents such as N,N-dimethylformamide, dimethylsulphoxide, acetonitrile or acetone; ether solvents such as tetrahydrofuran or dioxane; alcohols such as methanol or ethanol; and a mixture of water and the above-mentioned solvents.
Examples of base include inorganic carbonates such as potassium carbonate, potassium bicarbonate, sodium carbonate or sodium bicarbonate; inorganic bases such as sodium hydroxide or potassium hydroxide; sodium methoxide; and sodium hydride.
The products of formula (1-9) can be isolated and purified from the reaction mixture using a known method, such as extraction, recrystallization or chromatography.
The compound of general formula (() according to the present invention has strong herbicidal activities against many kinds of weeds and very weak phytotoxicities to useful crops. - . .
When the compound represented by general formula (I) is used as a herbicide, it is mixed with an agriculturally and horticulturally acceptable carrier, diluent or additive and adjuvant by a known method while being formed into a formulation which is usually employed as agricultural chemicals, for example, wettable powder; granule, wafer-dispersible granule, emulsion concentrate or suspension concentrate. The compound may be mixed or used together with other agricultural chemicals, for example, fungicides, insecticides, miticides, herbicides, plant growth regulators, fertilizers and soil conditioners.
!n particular, the mixed use with other herbicides can lead not only fo reductions in doses, reductions in manpower, but also to the broadening of the herbicidal spectrum attributable to cooperative activities and further improved effects attributable to synergistic activities by the both agents.
The following can, for example, be mentioned as specific examples of other herbicides usable in a state such that they are mixed with the compounds of the present invention represenfed by general formula (() (the term in parentheses denote common names unless otherwise defined).
TM
Methyl 3,4-dichlorophenylcarbamate (Swep), isopropyl 3-chlorophenylcarbamate TM TM
(Chloroproham), S-(4-chlorobenzyi)-diethylthiocarbamate (Benthiocarb), S-ethyl N,N-hexamethylenethiocarbamate (Molinate), S-(1-methyl-1-phenylethyi)-piperidine-1-carbothioate (Dimepiperafe), S-benzyl N-ethyl-N-(1,2-dimethylpropyl) thiolcarbamate TM
(Esprocarb), 3-(methoxycarbanyl)aminophenyl N-(3-mefhytphenyi) carbamate TM TM
(Phenmedipham), ethyl 3-phenyicarbamoyloxyphenyicarbamate (Desmedipham), etc.
urea h _rbi ides :~"
1-(a,a-Dimethyibenzyl)-3-(4-methylphenyi)urea (Dymron),.3-{3,4-dichiorophenyl)-1,1-dimethylurea (Diurov), 'i,1-dimethyl-3-(a,a,a-trifluoro-m-tolyl}urea (Fluometuron), 3-TM
(4-(4-chioroptienoxy)phenyl]-1,1-dimethyiurea (Chloroxuron), 3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea (Linuran), 3-(4-chlorophenyl)-1-methoxy-1_methylurea TM - TM
(Monolinuron), 3-(4-bromo-3-chlorophenyl)-1-methoxy-1-methylurea (Chlorbromuron), 1-TM
(a,a-dimethylbenzyl)-3-(2-chlorobenzyl)urea (Code number JC-940), etc.
)-laloacetarnide herb' itc des.
2-chloro-2',6'-diethyl-N-methoxymethytacetaniiide (Alachlor), N-butoxymethyl-2-TM
chloro-2',6'-diethylacetanilide (Butachlor), 2-chloro-2',6'-diethyl -N-(2-propoxyethyl) TM TM
acetanilide (Pretilachlor), 2-chloro-N-isopropyiacetanifide (Propachior), etc.
Amide~.r fides TM
3',4'-Dichioropropionanilide (Propanil), 2-bromo-N-(1,1-dimethylbenzyl)-3,3-dimetiiyibutanamide (Bromobutide), 2-benzothiazol-2-yloxy-N-methylacetanilide TM TM
(Metenacet), N,N-dimethyldipf~enylacetamide (Diphenamid), etc.
Dinitro~e~~l he_rbiside~
TM TM
4,6-dinitro-o-cresol (DNOC), 2-tent-butyl-4,6-dinitrophenol (Dinoterb), 2-sec-butyl-4,6-dinitrophenol (Dinoseb), N,N-diefhyl-2;6-dinitro-4-trifluoromethyl-m-phenylenediamine (Dinitramine), a,a,a-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine TM TM
(Trififuralin), 4-methyl-sulfonyl-2,6-dinitro-N,N-dipropylanifine (Nitralin), N-(1-ethylpropyl)-TM
2,6-dinitro-3,4-xylidine (Pendimethafin), etc.
p~lP,~lpXy herbs:idgs 2,4-Dichforophenoxyacetic acrd (2,4-D), 2,4,6-trichforophenoxyacetic acid (2,4,6-TM TM
T), 4-chloro-o-tolyloxyacetic acid (MCPA), S-ethyl-(4-chloro-2-methylphenoxy)-TM TM
ethanethioate (MCPA thioethyl), 4-(4-chforo-o-tolyfoxy) butyric acid (MCPB), 4-(2,4-TM
dichlorophenoxy) butyric acid (2,4-DB}, 2-(4-chloro-o-tolyloxy) propionic acid TM TM
(Mecoprop), 2-(2,4-dichlorophenoxy) propionic acid (Dichiorprop), {RS)-2-(4-(2,4-TM
dichlorophenoxy)phenoxyJ propionic acid (Diclofop) and its esters, (RS)-2-[4-(~-trifluoromethyl-2-pyridyloxy)phenoxyJ propionic acid.(F(uazifop) and its esters, 2-(2,4-dichloro-3-methylphenoxy) propionanilide (Clomeprop), S-ehtyl 4-chloro-2-TM TM
methylphenoxy-thioacetate (Phenothiol), 2-(2-naphthoxy) propionanilide (Naproanilide), etc.
Ca, rboxil~r,~~3cid herbi~id 2,2-Dichloropropionic acid (Dalapone), trichloroacetic acid (TCA), 2,3,6-~ TM
trichlorobenzoic acid (2,3,6-TBA), 3,6-dichloro-o-_ anisic acid (Dicamba), 3-amino-2,5-dichlorobenzoic acid (Chloramben), etc.
0-Ethyl O-(2-vitro-5-methylphenyl)-N-sec-butyl-phosphoramidethioate TM
(Butamifos), 0,0-diisopropyl S-(2-benzenesulfonylaminoehtyl)phosphorodithioate (SAP), S-(2-methyipiperidin-1-yl) carbonylmethy) O,O-dipropyl-phosphorodithioate TM
(Piperophos), etc.
F3 nzonifrll~bicidQ~
TM
2,6-Dichlorobenzonitrite (Dichlobenil), 3,5-dibromo-4-hydroxybenzonitrile TM TM
(Bromoxynil), 4-hydroxy-3,5-diiodobenzonitrile (laxynil), etc.
Dinhenylether herbicide TM
2,4-Dichlorophenyl 4-nitrophenyl ether (Nitrofen), 2,4,6-trichlorophenyl 4'-TM
nitrophenyl ether (Chlornitrofen), 2,4-dichlorophenyl 3-methoxy-4-vitro-phenyl ether ,.M TM
(Ghlomethoxyfen), ri~ethyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate (Bifenox), ~, nitrophenyl a,a,a-triffuoro-2-vitro-p-Poly! ether (Fluoroditen), 2-chloro-4-trifiiuoromethyiphenyl 3-ethoxy-4-nitrophenyt ether (Oxyfluorfen); 5-(2-chloro-a,a,a-trifluoro-p-tolyloxy)-2-nitrobenzoic acid (Acifluorfen), etc. , -Cia~'~rse~rbi id ~
4-Amino-3-methyl-6-phenyl-1,2,4-triazin-5(4H)-one (Metamitron), 4-amino-6-tert-butyl-3-methylthio-1,2,4-triazin-5(4H)-one (Metribuzin), 2-chloro-4,6-bis-(ethylamino)-TM
1,3,5-triazine (Simazine)., 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine .
TM TM
(Atrazin), 2,4-bis(ethylamino)-6-methylfhio-1,3,5-triazine (Simetryn), 2,4-TM
bis(isopropylamino)-6-methylthio-1,3,5-triazine (Prometryn), 2-(1,2-TM
dimethylpropylamino)-4-ethylamino-6-methy(thio-1,3,5-triazine (Dimethametryn), etc.
Sulfon~rlurea H~ i id _~
2-Chloro-N-(4-methoxy-6-methyl-1,3,5-triazin-2-yi) aminocarbonytj TM
benzenesulfonamide (Chlorosuifuron), methyl 2-{(((4,6-dimethoxypyrimidin-2-yl) TM
aminocarbonyl) aminosulfonylj methyl}benzoate (Bensulfuron meth yl), ethyl 2-(((4-chforo-6-methoxypyrimidin-2-yl) aminocarbonylJaminosulfonyl}benzoate (Chlorimuron TM
ethyl), etc.
D~7inQ~bic:ido~
TM
4-(2,4-Dichlorobenzoyl)-1,3-dimethylpyrazol-5-yl-p-toluenesulfonate (Pyrazolate), , TM
1,3-dimethy!-4-(2,4-dichlorobenzoyl)-5-phenacyloxypyrazole (Pyrazoxyfen), 1,3-dimethy!-4-(2,4-dichloro-3-methyl-benzoyt)-5-(4-methylphenacyloxy) pyrazole (Benzofenap), etc. .
Other herbicides TM
3,6-Dichloropyridine-2=carboxylic acid (Clopyralid), 4-amino-3,5,6-TM
trichloropyridine-2-carboxylic acid (Picloram), 5-amino-4-chloro-2-phenyl-pyridazin-3(2H)-one (Chloridazon), 3-cyclohexyf-1,5,6,7-tetrahydrocyclo pentenopyrimidine-TM TM
2,4(3H)-dione (LenaciJ), 5-bromo-3-sec-butyl-6-methy)uracil (Bromacil), 3-tent-butyl-5-chloro-6-methyuracile (Terbacil), 3-isopropyl-(1H)-2,1,3-benzofhiadiazin-~!(3H)-one-2,2-TM TM
dioxide (Bentazone), N-1-naphthyiphthalamic acid (Naptalam), etc.
As the agriculturally and horficutturally acceptable carriers or diluents used in the formulation of the compounds of this invention alone or in mixing with other herbicides, solid or liquid carriers usually used in agriculture may be used.
Examples of such solid carriers or diluents include clays represented by kaolinites, montmorillonites, illites, palygorskites, etc., more specifically pyrophyllite, attapulgite, sepiolite, kaolinite, bentonite, vermiculite, mica, talc, etc.;
and other inorganic substances such as gypsum, calcium carbonate, dolomite, diatomaceus earth, magnesium line, phosphorus lime, zeoiite, silicic anhydride, synthetic calcium silicate, etc.; organic substances of vegetable origin such as soybean flour, tobacco flour, walnut 2~765b7 flour, wheat flour, wood flour, starch, crystalline cellulose, etc.; synthetic or natural polymers such as coumarone resin, petroleum resin, alkyd resin, polyvinyl chloride, polyalkylene glycol, ketone resin, ester gum, copal gum, dammar gum, etc.;
waxes such as carnauba wax, beeswax, etc.; or urea and the like.
Examples of suitable liquid carriers or diluents include paraffin or naphthene hydrocarbons such as kerosene, mineral oil, spindle oil, white oil, etc.;
aromatic hydrocarbons such as xylene, ethylbenzene, cumene, methylnaphthalene, etc.;
chlorinated hydrocarbons such-as trichloroethylene, monochlorobenzene, o-chlorotoluene, etc.; ethers such as dioxane, tetrahydrofuran, etc.; ketones such as acetone, methyl ethyl ketone, diisobutyl ketone, cyclohexanone, acetophenone, isophorone; esters such as ethyl acetate, amyl acetate, ethylene glycol acetate, diethylene glycol acetate, dibuty) maleate, diethyl succinate, etc.; alcohols such as methanol, n-hexanol, ethylene glycol, diethylene glycol, cyclohexanol, benzyl alcohol,.
etc.; ether alcohols such as ethylene glycol ethyl ether, diethyiene glycol butyl ether, etc.; polar solvents such ass dimethylformamide, dimethyl suifoxide, etc., or water.
In addition, surfactants and other auxiliary agents may be used for various purposes such as emulsification, dispersion, humidification, spreading, dilation, .
combination destruction control, stabilization of active ingredients, improvement of flowability, prevention of corrosion, prevention of freezing, etc., of the compounds of the invention.
As the surfactant, although one of nonionic, anionic, cationic and amphoteric surfactants may be used, nonionic and (or) anionic sun'actants are usually used.
Examples of suitable nonionic surfactants include addition polymerization products of ethylene oxide with higher alcohols such as lauryl alcohol, stearyl alcohol, oleyl alcohol, etc.; addition polymerization products of ethylene oxide with aikylnaphthols such as butylnaphthol, octylnaphthol, etc.; addition polymerization products of ethylene oxide with higher fatty acids such as palmitic acid, stearic acid, oleic acid, etc.;
higher fatty acid esters of polyhydric alcohols such as sorbitan, and addition polymerization products of ethylene oxide therewith; etc.

_~8_ As suitable anionic surfactants, there can be cited, for example, alkyl sulfate salts such as sodium laurylsulfate, amine salts of sulfuric acid ester of oleyl alcohol, etc., alkyl sulfonate salts such as sodium dioctyl sulfosuccinate, sodium 2-ethylhexylsulfonate, etc., arylsulfonate salts such as sodium isopropyl naphthalenesulfonate, sodium methylene bisnaphthalenesulfonate, sodium lignosulfonate, sodium dodecyl benzenesulfonate, etc., and the like.
Further, for the purpose of improving the properties of formulations, enhancement of effects, etc., the herbicides of this invention may be used in combination with polymers and other auxiliary agents such as casein, gelatin, albumin, glue, sodium alginate, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, polyvinyl alcohol, etc.
The above-described carriers or diluents and various auxiliary agents are used singly or in combination with others depending on the purpose taking into consideration forms of formulation, conditions of application, etc.
The contents of active ingredients in the various formulations of this invention thus prepared may vary widely depending on forms of formulation, and suitable content is within the range of usually 0.1 to 99 % by weight, and preferably 1 to 80 %
by.weight, which is most suitable.
Wettable powder contain active ingredient compounds in amounts of usually 25 to 90 %, and the remainder solid carriers or diluents and dispersion wetting agents. If necessary, colloid protection agents, defoaming agents, etc. may be added thereto.
Granule contain, for example, active ingredient compounds in amounts of usually 1 to 35 %, and the remainder may be solid carriers or diluents and surfactants. The active ingredient compounds may be mixed with solid carriers or diluents uniformly, or fixed to or adsorbed on the surfaces of solid carriers or diluents uniformly.
It is preferred that the diameter of the granules be within the range of about 0.2 to 1.5 mm.
Emulsion concentrate contain, for example, active ingredient compounds of usually 5 to 30 %, and in addition about 5 to 20 % by weight of emulsifiers, the remainder being liquid carriers or diluents. If necessary, spreading agents and ~~~~5E1 anticorrosive agents may be added thereto.
Suspension concentrate contain, for example, active ingredient compounds in amounts of usually 5 to 50 %, and in addition 3 to 10 % by weight of dispersion wetting agents, with the remainder. being water. If necessary, protective colloid agents, preservatives, defoaming agents, etc. may be added thereto.
The compounds of this invention may be used as herbicides as they are or in any forms of formulation described above.
The herbicides of this invention may be applied in effective amounts to various places to be protected, for example, farm-lands such as paddy fields and upland, or non-crop lands, prior to germination of weeds or to weeds of various stages from after germination to growth period. The dose is generally, as amount of active ingredients, on the order of 0.7 to 10,000 glha, preferably 7 to 5,000 g/ha. The dose may be varied properly depending on the kind of objective weeds, their growth stages, places of application, weather, etc.
The compound of formula (1) and the herbicide provided by this invention have strong herbicidal activities against many kinds of weeds and very weak phytotoxicities to useful crops, as will be apparent from the test examples described later on.
For example, the compound of this invention exhibits excellent herbicidal effects at very low doses over a wide range of time from germination to and including the growth period of annual weeds such as Echinochloa crus-galfr, Cyperus ditformis, Monochoria vaginalis, Rotala indica, Lindernia procumbens, Dopafrium junceum, Eleocharis acicularis, and Alisma canaliculatum, and perennial weeds such as Scirpus juncoides, and Cyperus serofinus, while simultaneously being very safe towards paddy field rice plants. Another feature of the compound of the present invention is that when applied to soil or stem and leaves, it exhibits high herbicidal activities on various weeds which also cause problems in uplands to include perennial and annual Cyperaceous weeds such as Cyperus rotundus, Cyperus esculontus, Cyperus brevifolius, Cyperus microiria, and Cyperus iria and Echinochloa crus-galli, Drigitaria sanguinalis, Setaria viridis, Poa annua, Sorghum halepense, Avena sativa, and Alopecurus myosuroides as well as broad-leaved weeds such as Polygonum Japathifolium, Amaranthus viridis, and Chenopodium album, while simultaneously being very safe toward soybeans, cotton, sugar beets, maize, upland rice plants, wheat, etc.
Further, the compound according to the present invention can be used not only in paddy fields, and uplands, but also in orchards, mulberry fields, lawns, and non-crop lands.
in addition, when the compound according to the present invention is used in combination with other known agricultural chemicals having herbicidal activities, they exhibit complete herbicidal effects on weeds which are difficult to control with each of the compounds applied alone, and effectively control various weeds by synergistic herbicidal effects at doses at which a single compound is not effective. They are also very safe towards paddy field rice plants, soybeans, cotton, sugar beets, maize, upland rice plants, wheat, etc., so that they can provide herbicides which are very useful in agriculture.
EXAMPLES
Next, production of the compound of formula (!) and the intermediate compound of formula (II) will be described in more detail in the following examples.
Example 1 To methyl 2-amino-2-methylbutyrate (2.62 g) was dropped at room temperature 37 % formalin (2.27 ~g), and the mixture was stirred for 4 h. Then the reaction mixture was dissolved in ether and washed with water. The organic phase was dried over magnesium sulfate, filtered and evaporated to get the captioned compound (2.80 g).
Example 2 To a mixture of 2,2,6-trimethyl-5-phenyl-4H-1,3-dioxin-4-one (2.18 g) and methyl 2-(N-methylenamino)-2-methylbutyrate (1.5 g) was added 20 ml of xylene, and the mixture was refluxed for 1 h. The solvent inias evaporated and the residue was pur~ied by chromatography on a silica gel column to get the captioned compound (2.4 g).
Example 3 To a solution of methyl 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-butyrate (1.91 g) in 20 ml of ethanol was added at room temperature 30 ml of aq. NaOH (0.3N). After stirring for 24 h, ethanol was evaporated, and the mixture was acidified by hydrochloric acid. The precipitate was filtered off and dried to get fhe captioned compound (1.36 g).
Example 4 To benzyl 2-amino-2-methylbutyrate (12.96 g) was dropped at room temperature 37 % formalin (7.62 g), and the mixture was stirred for 4 h. The reaction mixture was dissolved in ether and washed with water. The organic phase was dried over magnesium sulfate, filtered and evaporated to get the captioned compound (13.7 g).
Example 5 To a mixture of 2,2,6-trimethyl-5-phenyl-4H-1,3-dioxin-4-one (13.97 g) and benzyl 2-(N-methylenamino)-2-methylpropionate (13.8 g) was added 130 ml of xylene, and the mixture was refluxed for 2 h. The solvent was evaporated and the residue was puri~ied by chromatography on a silica gel column to get the captioned compound (21.1 g).

~~~b~b~

Example 6 To a solution of benzyl 2-methyl-2-{6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yi)-propionate (21.1 g) in 100 ml of ethanol was added 1 g of 5% Pd on carbon and hydrogenated at room temperature under normal pressure. After ethanol was evaporated, saturated aq. sodium bicarbonate was added to the mixture and the catalyst was filtered off. The filtrate was acidified by hydrochloric acid. The precipitate was fltered off and dried to get the captioned compound ('! 0.8 g).
Example 7 To a mixture of 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid (0.83 g) and potassium carbonate {0.45 g) in 4 ml of dimethylformamide (DMF) was added ethyl iodide (0.56 g), and the mixture was stirred at 80 °C for 5 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica gel column ~o get the captioned compound (0.87 g).
Example 8 To a suspension of 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid (1.1 g) in 14 ml of CC14-CH2C12 (1:1 ) was added triphenylphosphin (1.38 g), then the mixture was refluxed for 40 min. The reaction mixture was ice-cooled and 3,5-dichlorophenol {0.65 g) and triethylamine (0.4 g) were slowly added, then it was stirred at room temperature for 1 h. After evaporation of the solvent, the residue was dissolved in ethyl acetate. The insolubles were filtered off and the filtrate was evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.7 g).
Example 9 To a suspension of 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid (0.83 g) in 10.4 m! of CC14 CHZCIZ (1:1) was added triphenylphosphin (1.04 g), then the mixture was refluxed for 40 min. The reaction mixture was ice-cooled and aniline (0.28 g) and triethylamine (0.3 g) were slowly added, then it was stirred at room temperature for 1 h. After evaporation of the solvent, the residue was dissolved in ethyl acetate. The insolubles were filtered off and the filtrate was evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.58 g).
Example 10 ' _ _' __ _-- __ _ _' r _ _ The captioned compound (1.05 g) was prepared in the same manner as described in Example 9 except 3,5-dichloroaniline was used as a starting material.
Example 11 pre ap ratiop~of N13-(trifluoromethyl~phenylj-2-methyl-2-(6-methyl-5-phenyl-2 3-dihydro-4-oxo -4H-1 3-oxazin-3- 1 ro anamide Com . No.93 The captioned compound (0.72 g) was prepared in the same manner as described in Example 9 except 3-(trifluoromethyl)aniline was used as a starting material.
Example 12 -To a solution of 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid {0.83 g) in 6 ml of tetrahydrofuran (THF) was added carbonyldiimidazole (0.59 g) . After stirring at room temperature for 30 min., isopropylamine (0.23 g) was added and the reaction mixture was stirred at 60°C for 5 h.
Then it was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.38 g)~
Example 13 A solution of N-{3,5-dichlorophenyl)-2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-oxo-4H-'f,3-oxazin-3-yl)-propanamide (0.6 g) in 2 ml of DMF was cooled in an ice bath and 60% sodium hydride in oii (0.06 g) was added. The mixture was stirred at room temperature for 30 min. and subsequently methyl iodide (0.31 g) was added and the mixture was stirred at room temperature for 5 h. Then the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.51 g).
Example 74 A solution of N-(4-methylthiophenyl)-2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propanamide (0.6 g) in 12 ml of 1,2-dichloroethane was cooled in an ice bath and 70% methachloroperbenzoic acid (0:8 g) was added.
After stirring at room temperature for_24 h, the reaction mixture was washed with saturated aq. sodium bicarbonate, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.5 g). ' Example 15 dihyrdro-4-oxo-4H-1 '~-oxa in-'~-yL~opanamide'( omndNo~,~.~1 The captioned compound (0.93 g) ) was prepared in the same manner as described in Example 9, except 2 fluoro-5-{trifluoromethyl)aniline was used as a starting material.
The physical properties of the various compounds prepared by the similar methods as described in the Examples are shown in Tables 1 to 6 previously mentioned, and'H-NMR data of those compounds are shown in Tables 7 and 8 below.

~~~~55~

Table 7 Compd. 'H-NMR (300MHz) a (ppm) Solvent CDCI, TMS=Oppm No.

1 1.72 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 7.07 (t,1H), 7.23-7.38 (m, 7H), 7.49 (d, 2H), 8.39 {brs,1 H) .

2 1.69 (s, 6H),1.96 (s, 3H), 5.32 (s, 2H), 6.95-7.3 (m, 8H), 8.i3 (brs,1H), 8.25-8.34 {m,1 H) .

3 1.70 {s, 6H), 1.95 (s, 3H), 5.30 (s, 2H), 6.70-6.80 (m, 1 H), 7.06-7.52 (m, 8H), 8.57 {brs, 1 H) .

4 1.71 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 6.91-7.46 (m, 9H), 8.41 (brs, 1 H) .

1.68 (s, 6H),1.96 (s, 3H), 5.34 {s, 2H), 7.00 (ddd,1 H), 7.20-7.37 (m, 7H), 8.38 {dd, i H), 8.42 (brs,1 H) ' 6 7.70 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 7.01-7.07 (m, 1H), 7.16-7.41 (m, 7H), 7.65 (t,1 H), 8.51 (brs, i H) .

7 1.70 (s, 6H), 1.95 (s, 3H), 5.30 (s, 2H), 7.20-7.48 (m, 9H), 8.50 (brs, 1 H) 9 1.70 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 7.10-7.42 {m, 8H), 7.78 (m,1 H), 8.50 {brs, i H) 12 i.69 (s, 6H),1.95 (s, 3H), 529 (s, 2H), 6.99 (t,1H), 7.22-7.47 {m, 7H), 7.94 {t,1H), 8.44 (brs, i H) i 4 1.68 (s, 6H),1.96 (s, 3H), 5.32 (s, 2H), 6.855 (m,1 H), 7.02 (m, 1 H), 7.22-7.37 (m, 5H), 8.05 (m,1 H), 8.19 (brs,1 H) 1.68 (s, 6H),1.96 (s, 3H), 5.32 (s, 2H), 6.77-6.92 (m, 2H), 7.20-7.38 (m, 5H), 8.05 (brs,1 H), 8.15-8.26 (m,1 H) 16 1.67 (s, 61-x, i.96 (s, 3H), 5.32 (s, 2H), 6.64-6.73 {m,1 H), 6.94-7.04 (m, 1 H), 7.2i-7.37 {m, 5H), 8.12-8.24 (m, 2H) . _ i7 1.7i (s, 6H),1.94 (s, 3H), 5.29 (s, 2H), 6.9i (m, 2H), 7.15 (m, iH), 7.26-7.39 (m, 5H), 7.93 (brs,1 H) 18 i.69 (s, 6H),1.95 (s; 3H), 5.30 (s, 2H), 6.98-7.10 (m, 2H), 7.22-7.39 (m, 5H), 7.54-7.63 (m, 1 H), 8.54 (brs, 1 H) 19 i.68 (s, 6H), i.95 (s, 3H), 5.29 (s, 2H), 6.50 (tt, iH), 7.11 {m, 2H), 7.22-7.40 (m, 5H), 8.67 (brs,1 H) 21 1.69 (s, 6H),1.95 (s, 3H), 5.29 (s, 2H), 7.22-7.40 (m, 5H), 8.16 (brs, 1 H) 22 1.67 {s, 6H), 1.97 (s, 3H), 5.34 (s, 2H), 7.16-7.37 (m, 7H), 8.34 (dd, 1 H), 8.51 (brs, 1 H) 23 1.66 (s, 6H), 1.96 (s, 3H), 5.33 (s, 2H), 7.20-7.38 (m, 7H), 8.35 (d, 1 H), 8.37 (brs, 1 H) 24 1.67 (s, 6H),1.96 (s, 3H), 5.33 (s, 2H), 6.98 (dd,1 H), 7.21-7.37 (m, 6H), 8.4i (brs, i H), 8.51 (d, 1 H) 26 1.69 (s, 6H), 1.95 (s, 3H), 5.30 (s, 2H), 7.21-7.39 (m, 7H), 7.75-7.78 (m, 1 H), 8.62 (brs, i H) ~~ ~~56~' -s~-Table 7 (continued) Compd. 'H-NMR (300MHz) b (ppm) Solvent CDCi, TMS=Oppm No.

27 1.69 (s, 6H),1.96 (s, 3H), 5.29 (s, 2H), 7.05 (t, i H), 7.22-7.40 (m, 5H), 7.48 (d,1 H), 8.66 (brs,1 H) 28 1.67 (s, 6H),1.95 (s, 3H), 5.29 (s, 2H), 7.22-7.40 (m, 5H), 7.62 (s, 2H), 8.72 (brs,1 H) 30 1.67 (s, 6H), 1.96 (s, 3H), 5.31 (s, 2H), 7.05-7.12 (m, 2H), 720-7.37 (m, 5H), 8.11 (brs,1 H), 8.21-8.28 (m, 1 H) 31 1.69 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 7.03 (t, 1 H), 7.21-7.40 (m, 6H), 7.69 (dd, 1 H), 8.51 (brs,1 H) 34 1.71 (s, 6H),1.95 {s, 3H), 2.22 (s, 3H), 5.31 {s, 2H), 7.03 (t,1H), 7.11-7.39 (m, 7H), 7.84 (d,1 H), 8.00 (brs,1 H) .

35 1.70 (s, 6H), 1.94 (s, 3H), 2.31 (s, 3H), 5.29 (s, 2H), 6.89 (d,1 H), 7.13-7.42 (m, 8H), 8.32 (brs, 1 H) 36 1.67 (s, 6H), 1.92 (s, 3H), 2.27(s, 3H), 5.27 (s, 2H), 7.07(d, 2t~, 7.21-7.39 (m, 7H), 8.25 {brs,1 H) 39 1.72 (s, 6H),1.95 (s, 3H), 5.32 (s, 2H), 6.85 (d,1H), 7.02 (d,1H), 7.23-7.38 (m, 5H), 7.71 (brs,1 H), 7.94 {brs,1 H) 40 1.76 (s, 6H),1.94 (s, 3H), 2.23 (s, 6H), 5.33 (s, 2H), 7.01-7.10 (m, 3H), 7.24-7.39 (m, 5H), 7.74 (brs, 1 H) .

42 1.70 (s, 6H),1.94 (s, 3H), 2.26 (s, 6H), 5.30 (s, 2H), 6.72 (brs,1 H), 7.14(brs, 2H), 7.23-7.38 (m, 5H), 8.27 (brs, 1 H) 46 ~ 1.67 (s, 6H), 1.96 (s, 3H), 2.46 (s, 3H), 5.33 (s, 2H), 7.21-7.38 (m, 6H), 8.30-8.37(m, i H), 8.21 (d,1 H), 8.45(brs,1 H) 49 1.21 (t, 3H), 1.71 (s, 6H),1.94 (s, 3H), 2.61 (q, 2H), 5.30 (s, 2H), 6.92 (d,1 H), 7.16-7.43 (m, 8H), 8.34 (brs, 1 H) 54 1.22 (d, 6H),1.72 (s, 6H),1.95 (s, 3H), 2.87 (sep,1 H), 5.30 (s, 2H), 6.95 (m,1 H), 7.17-7.38 (m, 7H), 7.42 (t,1 H), 8.34 (brs,1 H) 63 1.69 (s, 6H), 1.96 {s, 3H), 3.81 (s, 3H), 5.33 (s, 2H), 6.80-7.04(m, 3H), 721-7.36(m, 5H), 8.34(dd,1 H), 8.48(brs,1 H) 64 1.69 (s, 6H), 1.94 (s, 3H), 3.77 (s, 3H), 5.28 (s, 2H), 6.62 (dd, 1H), 6.92 (dd, 1H), 7.16 (t,1 H), 7.21-7.37 (m, 6H), 8.37 (brs,1 H) 65 1.70 (s, 6H), 1.94 (s, 3H), 3.77 (s, 3H), 5.29 (s, 2H), 6.82 (d, 2H), 7.22-7.44 (m, 7H), 8.23 (brs, 1 H) 72 1.66 (s, 6H), 1.94 (s, 3H), 5.29 (s, 2H), 7.22-7.40 {m, 5H), 7.44 (s, 2H), 8.38 (brs, 1 H) 73 1.68 (s, 6H), 1.95 (s, 3H), 5.29 (s, 2H), 7.22-7.40 (m, 5H), 7.66 (s, 2H), 8.41 {brs, 1 H) 88 1.68 (s, 6H), 1.94 (s, 3H), 5.28 (s, 2H), 6.72 (dd,1 H), 6.99 (dd, 2H), 7.07 (t, 1 H), 7.20-7.40(m, 1 OH), 8.37(brs, 1 H) Table 7 (continued) Compd. 'H-NMR (300MHz) b (ppm) Solvent CDCI, TMS=Oppm No.

92 1.65 (s, 6H),1.96 (s, 3H), 5.3i (s, 2H), 7.11-7.36 (m, 6H), 7.48-7.60 (m, 2H), 823 (brs,1 H), 8.37 (d, i H) 93 1.72 (s, 6H),1.96 (s, 3H), 5.31 (s, 2H), 7.21-7.42 (m, 7H), 7.65 (d,1 H), 7.85 (brs,1 H), 8.64 (brs,1 H) .

94 1.7i (s, 6H),1.96 (s, 3H), 5.31 (s,~2H), 7.21-7.39 (m, 5H), 7.53, 7.62 (ABq, 4H), 8.73 (brs,1 H) .

95 1.65 (s, 6H),1.97 (s, 3H), 5.32 (s, 2H), 722-7.36 (m, 5H), 7.41 (brd, 1 H), 7.69 (brd, 9 H), 8.41 (brs,1 H), 8.86 (hrs, i H) ' 96 i.68 (s, 6H), 1.96 (s, 3H), 5.32 (s, 21-~, 72i-7.37 (m, 5H), 7.49 (brs, 1 H), 7.96 (brs, i H), 8.92 (brs,1 H) 102 1.67 (s, 6H),1.95 (s, 3H), 5.32 (s, 2H), 6.40 (t,1H), 6.99-7.i0 (m, 2H), 7.16-7.36 (m, 6H), 8.40(dd,1 H), 8.45(brs,1 H) 103 1.70 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 6.50 (t,1 H), 6.80-6.83 (m, 1 H), 7.19-7.39 (m, 7H), 7.50(brs,1H), 8.53(brs,1H) 104 1.70 (s, 6H),1.95 (s, 3H), 5.30 (s, 2H), 6.43 (t,1 H), 7.04,7.48 (ABq, 4H), 7.22-7.39 (m, 5H), 8.46 (brs,1 H) 110 1.67 (s, 6H),1.94 (s, 3H), 5.29 (s, 2H), 6.90 {m,1 H), 7.20-7.37 (m, 7H), 7.57 (brs,1 H), 8.57 (brs,1 H) '123 1.65 (s, 6H),1.94 (s, 3H), 5.31 (s, 2H), 721-7.36 (m, 7H), 7.57-7.65 (m,1 H), 7.s7 (brs,1 H), 8.64 (brs,1 H) 124 1.71 (s, 6H), 1.96 (s, 3H), 5.30 (s, 2H), 7.20-7.39 {m, 5H), 7.56, 7.63 (ABq, 4H), 8.90 (brs,1 H) 127 1.67 (s, 6H), 1.99 (s, 3H), 5.39 (s, 2H), 7.12 (ddd,1 H), 7.7 8-7.34 (m, 5H), 7.61 (t, 1 H), 8.19(dd,1 H), 8.81 (dd, 1 H), 71.01 (brs,1 H) 128 1.70 (s, 6H), 1.96 (s, 3H), 5.32 (s, 2H), 7.21-7.45 (m, 6H), 7.85-7.92 (m, 2H), 8.33-8.37 (m,1 H), 8.74 (brs,1 H) 129 1.71 (s, 6H),1.96 (s, 3H), 5.32 (s, 2H), 7.20-7.40 {m, 5H), 7.67, 8.15 (ABq, 4H), 9.06 (firs, 7 H) 131 1.69-(s, 6H), 1.98 (s, 3H), 5.35 (s, 2H), 7.22-7.38 (m, 5H), 8.64 (t,1 H), 8.67 (d, 2H), 9.25 (brs, 1 H) 135 1.88 (s, 6H), 1.96 (s, 3H), 3.84 (s, 3H), 5.42 (s, 2H), 7.02 (ddd,1 H), 7.18-7.35 (m, 5H), 7.49 (ddd,1 H), 7.98 (dd,1 H), 8.71 (dd, 1 H),11.52 (brs,1 H) 137 1.85 (s, 6H), 1.92 (s, 3H), 3.85 {s, 3H), 5.28 (s, 2H), 7.20-7.35 (m, 5H), 7.57, 7.92 {ABq, 4H), 8.65 (brs,1 H) 138 1.37 (t, 3H), 1.69 (s, 6H), 1.95 (s, 3H), 4.35 (q, 2H), 5.31 (s, 2H), 7.20-7.38 (m, 6H), 7.74 (d,1 H), 7.88 (dd, 1 H), 7.99 (brs,1 H), 8.39 (brs, 1 H) _ ~~~65~7 Table 7 (continued) Compd. 'H-NMR (300MHz) a (ppm) Solvent CDCI, TMS=Oppm No. _ 141 1.69 (s, 6H),1.95 (s, 3H), 3.77 (s, 3H), 4.62 (s, 2H), 529 (s, 2H), 6.65 (dd,1 H), 7.01 (d,1 H), 7.14-7.38(m, 7H), 8.41 (brs, 1 H) 144 1.58 (d, 3H),1.68 (s, 6H),1.94 (s, 3H), 3.71 (s, 3H), 4.77(q,1 H), 5.28 (s, 2H), 6.60 (dd, i H), 7.04 (d,1 H), 7.12-7.38 (m, 7H), 8.39 (brs,1 H) 146 1.69 (s; 6H),1.96 (s, 3H), 2.26 (s, 3H), 5.36 (s, 2H), 7.Oi (t,1 H), 7.20-7.35 (m,SH), 7.45 (dd,1 H), 8.38 (dd,1 H), 9.08 '(brs,1 H) 147 1.71 (s, 6H),1.95 (s, 3H), 2.47 (s, 3H), 5.30 (s, 2H), 6.94-6.99 {m, 1 H), 7.16-7.39 (m, 7H), 7.5s (brs,1 H), 8.3s (brs,1 H) 148 1.69 (s, 6H),1.94 (s, 3H), 2.44 (s, 3H), 529 {s, 2H), 7.18-7.48 (m, 9H), 8.38 (brs, i H) 149 1.67 (s, 6H),1.96 (s, 3H), 2.59 (s, 3H), 5.43 (s, 2H), 7.16(t, i H), 7.25-7.38 (m, 5H), 7.56 (t;1 H), 7.85 (dd,1 H), 8.30 (d, 1 H), 9.99 (d,1 H) 151 1.67 (s, 6H),1.95 (s, 3H), 2.99 (s, 3H), 5:3i (s, 2H);
7.20-7.40 (m, 5H), 7.67, 7.78 {ABq, 4H), 8.79 (brs,1 H) 152 1.65 (s, 6H),1.94 (s, 3H), 5.32 (s, 2H), 6.5-6.6 (m, 1 H), 6.7-6.8 (m,1 H), 7.1-7.4 (m, 7H) 155 1.70 (s, 6H),1.96 (s, 3H), 2.59 (s, 3H), 5.32 (s, 2H), 721-7.42 (m, 6H), 7.66 (dd, 1 H), 7.79-7.86 (m,1 H), 8.01-8.04 (m,1 H), 8.42 (brs,1 H) 187 1.10 (t, 3H),1.70 (s, 6H), 2.23 (q, 2H), 5.30 (s, 2H), 7.0-7.7 (m, 9H), 8.5i {brs,1 H) 204 1.12 (t, 3H),1.73 (s, 6H), 2.22 (q, 2H), 5.33 (s, 2H), 7.2-7.9 (m, 9H), 8.64 (brs,1 H) 211 0.88 (t, 3H),1.4-1.65 (m, 2H),1.71 (s, 6H), 2.20 (t, 2H), 5.31 (s, 2H), 7.0-7.7 (m, 9H), 8.52 (brs, i H) -214 1.71 (s, 6H),1.93 (s, 3H), 5.33 (s, 2H), 7.04-7.17 (m, 3H), 7.25-7.35 (m, 4H), 7.49 (d, 2H), 8.37 (brs,1 H) 215 1.69 (s, 6H), 1.94 (s, 3H), 5.32 (s, 2H), 7.01-7.24 (m, 4H), 7.24-7.35 (m, 3H), 7.64 (t,1 H), 8.48 (brs,1 H) 220 1.67 (s, 6H), 1.94 (s, 3H), 5.32 (s, 2H), 7.04 (t, 1H), 7.04-7.18 (m, 2H), 7.26-7.31 (m, 2H), 7.47 (d, 2H), 8.60 (brs,1 H) 298 1.59 (s, 6H), 1.74 (s, 3H), 3.19 (s, 3H), 4.20 (brs, 2H), 7.14-7.20 (m, 2H), 7.26-7.42 (m, 8H) 302 1.57 (s, 6H),1.82 (s, 3H), 3.21 (s, 3H), 4.66 (brs, 2H), 7.15 (d, 2H), 7.26-7.40 (m, 6H) 339 1.66 (s, 6H), 1.96 (s, 3H), 5.31 (s, 2H), 7.22-7.37 (m, 5H), 7.93 (m, 1 H), 8.90 (brs,1 H) 341 1.72 (s, 6H), 1.96 (s, 3H), 5.30 (s, 2H), 6.86 (m, 1 H), 7.14 (m, 1 H), 7.25-7.40 (m, SH), 8.09 (brs, 1 H) 342 1.66 (s, 6H), 1.95 (s, 3H), 5.31 (s, 2H), 6.93 (m, 1 H), 7.21-7.38 (m, 5H), 8.1'1 (brs,1 H), 8.26 (m, 1 H) _ 2~ ~~561 Table 7 (continued) Compd. 'H-NMR (300MHz) a (ppm) Solvent CDCI, TMS=Oppm No.

343 1.72 (s, 6H), 1.95 (s, 3H), 529 (s, 2H), 6.71 (m, 2H), 7.23-7.40 (m, 5H), 7.93 (brs, 1 H) 344 1.65 (s, 6H),1.96 (s, 3H), 5.30 (s, 2H), 7.18-7.40 (m, 5H), 8.01-8.14 (m, 1 H), 8.19 (bts,1 H) 345 1.70 (s, 6H),1.95 (s, 3H), 529 (s, 2H), 6.76-6.87 (m,1 H), 724-7.40 (m, 5H), 8.03 (brs,1 H) 346 1.70 (s, 6H), 1.95 (s, 3H), 5.29 (s, 2H), 6.94 (m, 1 H), 7.25-7.40 (m, 5H), 8.19 (bts,1 H) 348 1.66 (s, 6H),1.95 (s, 3H), 5.32 (s, 2W), 7.21-7.36 (m, 5H), 7.43 (s,1 H), 8.38 (brs,1 H), 8.63 (s,1 H) 349 1.64 (s, 6H),1.96 (s, 3H), 5.31 (s, 2H), 7.20-7.36 (m, 5H), 8.49 (brs,1H), 8.62 (s,1H) 350 1.67 (s, 6H), 1.96 (s, 3H), 5.32 (s, 2H), 6.95-7.00 (m, 2H), 7.22-7.37 (m, SH), 8.17 (brs,1 H), 8.39-8.43 (m,1 H) 353 1.67 (s, 6H),1.96 (s, 3H), 5.31 (s, 2H), 7.20-7.37 (m, 8H), 8.13 (brs,1 H), 8.21 (t, 1 H) 354 1.70 (s, 6H), i.96 (s, 3H), 529 (s, 2H), 7.24-7.40 (m, 5H), 825 (brs,1H) 336 1.30 (s,18H),1.72 (s, 6H),1.95 (s, 3H), 5.31 (s, 2H), 7.15 (m,1H), 7.23-7.38 (m, 7H), 826 (brs,1 H) 357 1.68 (s, 6H),1.95 (s, 3H), 2.29 (s, 3H), 5.32 (s, 2H), 6.79 (m,1 H), s.88-s.96 (m,1 H), 7.22-7.38 (m, 5H), 8.06 {brs, 1 H), 8.13 (dd,1 H) 361 1.68 (s, 6H), 1.95 (s, 3H), 2.49 (s, 3H), 5.29 (s, 2H), 7.23-7.39 (m, 5H), 7.73 (s, 2H), 8.46 (brs,1 H) 362 1.67 (s, 6H),1.97 (s, 3H), 5.32 (s, 2H), 7.17-7.38 (m, 7H), 8.22 (brs,1 H), 8.52 (t,1 H) 363 1.69 (s, 6H), 1.96 (s, 3H), 5.33 (s, 2H), 7.15 (t, 1H), 7.21-7.38 (m, 6H), 8.3i (brd, 1H), 8.71 (dd,1 H) 364 1.70 (s, 6H), 1.95 (s, 3H), 5.31 (s, 2H), 7.10 (t,1 H), 722-7.40 (m, 5H), 7.65 (m, 1 H), 7.79 (dd,1 H), 8.fi1 (brs,1 H) 365 1.69 (s, 6H), 1.95 (s, 3H), 5.31 (s, 2H), 7.20-7.40 (m, 6H), 7.64 (dd, 1H), 7.86 (d, 1H), 8.68 (brs, 1 H) 369 1.66 (s, 6H), i .93 (s, 3H), 5.28 (s, 2H), fi.4-6.6 (m, 1 H), 6.84 (brs,1 H), 6.9-7.4 (m, 11 H), 8.42 {brs, 1 H) 370 1.68~(s, 6H), 1.94 (s, 3H), 5.30 (s, 2H), 6.84 (s,1 H), 7.09 (dd,1 H), 7.2-7.4 (m, 5H), 7.63 (d,1 H), 8.23 (brs, i H) 371 1.35 (d, 6H),1.67 (s, 6H),1.96 (s, 3H), 4.53 (sep, 1 H), 5.32 (s, 2H), 7.09 (d,1 H), 7.2-7.4 (m, 5H), 8.10 (d,1 H), 8.10 (brs, 1 H) 376 1.65 (s, 6H),1.94 (s, 3H), 5.32 (s, 2H), 7.10 (dd, 1 H), 7.21-7.36 (m, 5H), 7.73 (m, 1 H), 8.7 5 (dd,1 H), 8.72 {brs,1 H) ~~7~5G1 Table 7 (continued) Compd. 'H-NMR (300MHz) a (ppm) Solvent CDCI, TMS=Oppm No.

506 1.66 {s, 6H),1.94 (s, 3H), 5.3i (s, 2H), 7.07 (d, 2H), 7.20 (t,1 H), 7.23-7.41 (m, 5H) 600 1.59 (s, 6Hj, i.92 (s, 3H), 5.26 (s, 2H), 7.06 (brs, 2H), 7.2-7.4 (m, 4H), 7.62 (brs,1H) 604 1.13 (d, 6H),1.61 (brs, 6H), 1.92 (s, 3H), 4.03 (sep, 1 H), 5.24 (s, 2H), 5.87 (d, 1 H), 720-7.38 (m, 5H) , 606 0.89 (d, 6H),1.61 (s, 6H);1.7-1.9 (m,1 H), 1.92 (s, 3H), 3.06 (t, 2H), 5.25 (s, 2H), 628 (brs,1 H), 7.2-7.4 (m, 4H) -608 1.33 (s, 9H),1.57 (s, 6H),1.91 (s,.3H), 523 (s; 2H), 5.91 (brs,1H), 7.22-7.38 (m, 5H) 611 1.48 {d, 3H),1.61 (s, 3H), 1.62 (s, 3H),1.90 {s, 3H), 5.09 (dq, 1 H), 5.19, 523 (ABq, 2H), 6.38 (d,1 H), 7.19-7.39 (m,1 OH) 612 1.60 (s, 6H),1.68 (s, 6H),1.91 (s, 3H), 521 (s, 2H), 6.46 (brs, 1 H), 7.18-7.42 (m,1 OH) 613 1.54 {s, 6H),1.91 (s, 3H), 2.80 (t, 2H), 3.50 (q, 2H), 5.19 (s, 2H), 6.18 (brt, 1 H), 7.16-7.38 (m, 10H) 624 1.59 (s, 6H),1.92 (s, 3H), 3.04 (brs, 6H), 5.20 (s, 2H), 7.2-7.4 (m, 5H) 634 1.59 (s, 6H),1.92 (s, 3H), 5.27 (s, 2H), 7.22-7.38 (rn, 5H) 635 1.55 (s, 6H), '1.92 (s, 3H), 5.27 (s, 2H), 7.20-7.37 (m, 5H) 636 122 (t, 3H), 1.55 (s, 6H),1.91 (s, 3H), 4.15 (q, 2H), 5.27 (s, 2H), 721-7.38 (m, 5H) 638 1.20 (d, 6H),1.59 (s, 6H),1.91 (s, 3H), 4.9-5.1 {m,1 H), 5.25 (s, 2H), 7.2-7.4 (m, 5H) 645 1.58 (s, 6H), 1.90 (s, 3H), 5.11 {s, 2H), 5.25 (s, 2H), 7.20-7.38 (m, 10H) 650 0.93 {t, 3H),1.53 (s, 3H),1.77-1.91 (m, 1 H), 1.93 (s, 3H), 2.21-2.36 (m,1 H), 522, 5.25 (ABq, 2H), 722-7.39 (m, 5H) 651 0.91 (t, 3H), 1.48 (s, 3H),1.75-1.89 (m,1 H),1.92 (s, 3H), 2.12-2.27 (m,1 H), 3.69 (s, 3H), 522, 5.25 (ABq, 2H), 7.23-7.38 (m, 5H) 683 1.57 (s, 6H), 1.88 (d, 3H), 5.11 (s, 2H), 5.28 (s, 2H), 7.02-7.16 (m, 2H), 7.24-7.33 (m, 2H), 7.30 (s, 5H) 687 1.07 (t, 3H),1.58 (s, 6H), 2.15 (q, 2H), 5.12 (s, 2H), 5.25 (s, 2H), 7.2-7.5 (m, 10H) 690 0.84 (t, 3H), 1.5-1.8 (m, 8H), 2.15 (t, 2H), 5.11 (s, 2H), 5.24 (s, 2H), 7.1-7.4 (m, 1 OH) Table 8 D c H~C~CH3 -~-- A
H C CH~
HZC.N~ORtt '~ /3 H~'N~H""-' B
O ' H3C~N~N~CH~
ttR02C CH~ H C_ c02Rt t Compel. 'H-NMR (300MHz) a (ppm) Solvent CDCI, TMS=Oppm No.

2-10 1.34 (s, 6H), 3.67 (s, 2H), 5.06 (s, 2H), 725-7.39 (m, SH) (trimer) 2-15 0.80-0.92 (m, 3H),1.28-1.42 (m, 3H);1.68-1.90 (m, 2H), 3.60-3.76 (m, 3H+B), 7.42, 7.48 (ABq, D) Next, several embodiments of formulations using the compound of this invention will be shown. In the following formulations, all "parts" are by weight.
Formulation Example 1 (Emulsion Concentrate) Compound No. 1 20 parts Xylene 63 parts Calcium dodecylbenzenesulfonate 7 parts Polyoxyefhylenestyryl phenyl ether 5 parts Dimethylformamide , 5 parts The above materials were uniformly mixed and dissolved, to obtain 100 parts of emulsion concentrate.
Formulation Example 2 (Wettable Powder) Compound No. 9 20 parts Kaolinite . 70 parts Calcium lignosulfonate 7 parts Condensate of alkylnaphthalenesulfonic acid 3 pads The above materials were mixed and crushed using a jet mill, to obtain 100 parts of wettable powder.

~~~~561 Formulation Example 3 (Suspension Concentrate) Compound No. 1 . 20 parts Sodium di(2-ethylhexy!)sulfosuccinate 2 parts Polyoxyethylene nonylphenylether ~ 2 parts Defoaming agent 0.5 parts .

Propylene glycol 5 parts ~

Xanthan gum ~ _ 0.01 parts Water ~ 70.49 parts The above materials were crushed and uniformly mixed by using a wet-type ball mill, to obtain 100 parts of suspension concentrate.
Formulation Example 4 (Granule) Compound lVo.1 1 parts Sodium di(2-ethylhexyl)suifosuccinate 2 parts Bentonite 30 parts Talc 67 parts The above materials were sufficiently mixed, kneaded with an addition of a suitable amount of water and granulated by a granulator to obtain 100 parts of a granule.
The herbicidal effects of the compound of this invention will be explained below according to the test examples.
Test Example 1 (Paddy field soil application) Paddy field soil was filled in 500 cm2 wagner pots, suitable amounts of water and chemical fertilizers were added thereto, and kneaded to convert it to a paddy field state.
A stock of paddy field rice plant (variety; Koshihikari) comprising a pair of two seedlings that had been grown in advance in a greenhouse to a stage of two leaves, were transplanted in each pot in a population of one stock per pot. Further, in each pot, there were sown predetermined amounts of seeds of Echinochloa crus-galli, Monochoria vaginalis, Lindernia procumbens and Scirpus juncoides, respectively, and water was filled to a depth of 3cm. ~ .
On the next day, wettable powders were prepared using the compounds shown in Table 9 below according to Formulation Example 2, and they were diluted with a suitable amount of water.so that they contained active ingredients in an amount of 50 g/ha. They were applied by dropping with a pipette.
After 29 days from the application with the chemicals, herbicidal effects on each weed and phytotoxicity on paddy field rice plants were evaluated according to the following criteria. The results obtained are shown in Table 9 below.
Evaluation criteria (1'i ranks) Score Herbicidal effects: Phytotoxicrty to crop:

Ratio of trifled weeds Ratio of injured plants compared compared to the t0 the COntfOf (%) COntfOf (%~

1 Above 0 to 10 2 Above 10 to 20 .

3 Above 20 to 30 -4 Above 30 to 40 Above 40 to ~0 Same as the left column 6 Above SO to fi0 7 Above 60 to 70 8 Above 70 to 80 9 Above 80 to 90 Above 90 to 100 (withered) ~~~6561 Table 9 Compd. Active - Herbicidal Phytotobcity No. ingredienteffects dose Weed A Weed B Weed Weed 0 Padd field g alma . . . C rice pl nt -- -1 50 10 10 . 10 10 0 6 50 ~ 10 - 10 10 10 0 22 50 . 10 ~10 10 10 0 24 50 10 10. 10 ~ 10 0 26 50 10 10' 10 9 0 39 50 10 10 i0 10 0 138 . 50 10 10 10 10 0 in the Tables 9-12, abbreviations of weeds are as follows.
Weed A: Echinochloa crus-galli Weed B: Monochoria vaginalis Weed C: Lindernia procumbens Weed D: Scripus Juncoides Weed E: Digitalia sanguinalis Weed F: Setaria viridis _ ~~~~561 - ss -Weed G: Abufilon fheophrasti Weed H: Xanthium strumarium Weed I: Polygonum lapathifolium Weed J: Datura stramonium Test Example 2 (Paddy field foliar application) Paddy field soil was filled-in 500 cm2 wagner pots, suitable amounts of water and chemical fertilizers were added thereto, and kneaded to convert it to a paddy field state.
A stock of paddy field rice plant (variety; Koshihikari) comprising a pair of two seedlings that had been grown in advance in a greenhouse to a stage of two leaves, were transplanted in each pot in a population of one stock per pot. Further, in each pot, there were sown predetermined amounts of seeds of Echinochloa crus~alli, Monochoria vaginalis, Lindernia procumbens and Scirpus juncoides, respectively, and wafer was filled to a depth of 3cm.
After having grown the plants in a greenhouse until Echinochloa crus~alli reached a stage of 1.5 leaves, wettable powders were prepared using the compounds shown in Table 10 below according to Formulation Example 2, and they were diluted with a suitable amount of water so that they contained active ingredients in an amount of 100 glha. They were applied by dropping with a pipette.
After 21 days from the application with the chemicals, herbicidal effects on each weed and phytotoxicity on paddy field rice plants were evaluated according to the criteria shown in Test Example 1 above. The results obtained are shown in Table 10 below.

~'l T 6561 -s7-Table 10 comps. Active Herbicidal Pnytotobcity No. ingredienteffects g a'Uha Weed Weed Weed C Weed Paddy field A B D rice plant 1 100 10 ~10 10 10 0 3 .100 ~10 ~ 10 10 . 10 0 ~

6 100 10 ~ 10 10 10 0 26 100 10 10 ' 10 8 0 Test Example 3 (Upland soil application) Upland soil was filled in 900 cm2 plastic pots, in which there were sown predetermined amount of seeds of Echinochloa crus-galli, Drigitaria sanguinalis, Setaria viridis, Abutilon theophrasti, Xanthium strumarium, Polygonum lapathifolium and Datura stramonium, respectively, and soil was placed thereon to a thickness of 1 cm.
On the day after sowing, wettable powders were prepared using the compounds _ ~~~6561 -s8-shown in Table 11 below according to Formulation Example 2, and they were diluted with a suitable amount of water so that they contained active ingredients in an amount of 9 kglha. They were sprayed uniformly over the surface of soil.
After 21 days from the application with the chemicals, herbicidal effects on each weed were evaluated according to the criteria shown in Test Example 1 above.
The results obtained are shown in Table 11 beloinr.
Table 11 c"'y Aaire ~ Herbicidal No. ingredienteffects ' dose Weed Weed Weed Weed Weed Weed Weed 6 100D 10 ~ 10 10 10 9 10 9 24 1000 10 10 i0 10 9 10 ' 9 Test Example 4 (Upland foliar application) Upland soil was filled in 900 cm2 plastic pots, in which there were sown predetermined amount of seeds of Echinochloa crus-galli, Drigifaria sanguinalis, Setaria viridis, Abutilon fheophrasti, Xanthium strumarium, Polygonum lapathifolium and Datura stramonium, respectively, and soil was placed thereon to a thickness of 1 cm.
After having grown the plants in a greenhouse until each plant reached a stage of from 2 to 4 leaves, wettable powders were prepared using the compounds shown in Table 12 below according to Formulation Example 2, and they were diluted with a ~~~6561 suitable amount of water so that they contained active ingredients in an amount of 1 kg/ha. They were sprayed uniformly over the surface of leaves.
After 21 days from the application with, the chemicals, herbicidal effects on each weed were evaluated according to the criteria shown in Test Example 1 above.
The results obtained are shown in Table 12 below.
Table 12 c~"~' ~"'e . ~ .
ISO. ltlgfEdefll Herbicidal dose Weed Weed effects Weed Weed g ailha A E I J
Weed F
Weed G
Weed H

1 1000 10 10 ~ 10 10 9_ 9 9 363 1000 10 10 10 ~ 10 I 9 ~ 10 , 8

Claims (23)

The embodiments of the present invention in which an exclusive property or privilege is claimed are defined as follows:

1. A 1,3-oxazin-4-one derivative represented by the formula (I):
in which R1 represents a phenyl group which may be substituted;
R2 represents a hydrogen atom or a C1-6 alkyl group;
R3 represents a hydrogen atom, a C1-6 alkyl group, an aralkyl group selected from the group consisting of benzyl, 1-phenylethyl, 2-phenylethyl, 1-methyl-1-phenylethyl, 1-methyl-2-phenylethyl, 1-ethyl-2-phenylethyl, and 3 -phenylpropyl or a phenyl group which may be substituted;
R4 and R5 each independently represent a C1-6 alkyl group;
and W represents an oxygen atom or a group represented by the formula -N(R6)- in which R6 represents a hydrogen atom, a C1-6 alkyl group, a C2-5 alkenyl group or a C2-5 alkynyl group;
wherein phenyl may be substituted in R1 or R3 with at least one substituent selected from a halogen atom, a hydroxy group, a C1-6 alkyl group, a C1-6 alkoxy group, a phenoxy group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group, a C1-6 haloalkyl group, a C1-6 haloalkoxy group, a C1-6 alkoxycarbonyl group, a C1-6 alkoxycarbonyl-C1-6 alkoxy group, an acyl group, a cyano group, and a nitro group.

2. The compound according to claim 1, wherein R1 is a phenyl group, a 2-fluorophenyl group, a 2-chlorophenyl group or a 2-methylphenyl group.

3. The compound according to claim 1 or 2, wherein R2 is a hydrogen atom, a methyl group or an ethyl group.

4. The compound according to claim 1, 2 or 3, wherein R3 is a phenyl group; a phenyl group substituted at the 3-position by one substituent selected from the group consisting of a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a phenoxy group, a C1-6 haloalkyl group and a C1-6 haloalkoxy group; or a phenyl group substituted at the 2- and 5-positions or 3- and 5-positions by two substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a phenoxy group, a C1-6 haloalkyl group and a C1-6 haloalkoxy group.

5. The compound according to any one of claims 1 to 4, wherein R4 and R5 are each independently a methyl group or an ethyl group.

6. The compound according to any one of claims 1 to 5, wherein W is a group represented by the formula -N(R6)- in which R6 is a hydrogen atom, a C1-6 alkyl group, a C2-5 alkenyl group or a C2-5 alkynyl group.

7. The compound according to any one of claims 1 to 5, wherein W is a group represented by the formula -NH- or -N(CH3)-.

8. A 1,3-oxazin-4-one derivative represented by following formula (I-1):
in which X1, X2 and X3 each independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a phenoxy group, a C1-6 haloalkyl group or a C1-6 haloalkoxy group.

9. The compound according to claim 8, wherein X1 is a fluorine atom, X2 is a hydrogen atom and X3 is a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a phenoxy group, a C1-6 haloalkyl group or a C1-6 haloalkoxy group.

10. The compound according to claim 8, wherein X1 is a hydrogen atom, X2 is a trifluoromethyl group and X3 is a hydrogen atom.

11. An N-methylene amino acid ester derivative represented by the following formula (II):
in which R4 and R5 each independently represent a C1-6 alkyl group, and R10 represents a C1-6 alkyl group or an aralkyl group selected from the group consisting of benzyl, 1-phenylethyl, 2-phenylethyl, 1-methyl-1-phenylethyl, 1-methyl-2-phenylethyl, 1-ethyl-2-phenylethyl and 3-phenylpropyl.

12. A herbicidal composition comprising a 1,3-oxazin-4-one derivative as defined in any one of claims 1 to 10, and an agriculturally and horticulturally acceptable carrier and/or diluent.

13. The herbicidal composition according to claim 13 which further comprises a herbicidally active ingredient selected from the group consisting of a carbamate derivative, an urea derivative, a haloacetamide derivative, a amide derivative, a dinitrophenyl derivative, a phenoxy derivative, a carboxylic acid derivative, an organophosphorous compound, a benzonitrile derivative, a diphenylether derivative, a triazine derivative, a sulfonylurea derivative and a diazine derivative.

14. The herbicidal composition according to claim 13 wherein the herbicidally active ingredient is selected from the group consisting of 2, 4-D TM, 2, 4-DB TM, 2, 4, 5-T TM, 2,3,6-TBA TM, Acifluorfen TM, Alachlor TM, Atrazin TM, Benthiocarb TM, Bensulfuron methyl TM, Bentazone TM, Benzofenap TM, Bifenox TM, Bromacil TM, Bromobutide TM, Bromoxynil TM, Butachlor TM, Butamifos TM, Chlorimuron ethyl TM, Clopyralid TM, Chloroproham TM, Chloroxuron TM, Chlorbromuron TM, Chloramben TM, Chloridazon TM, Clomeprop TM, Chlornitrofen TM, Chlorosulfuron TM, Chlomethoxyfen TM, Code number JC-940TM, Dalapone TM, Desmedipham TM, Dicamba TM, Dichlorprop TM, Diclofop TM, Dichlobenil TM, Dimethametryn TM, Dimepiperate TM, Diphenamid TM, DNOC TM, Dinoterb TM, Dinoseb TM, Dinitramine TM, Dymron TM, Diuron TM, Esprocarb TM, Fluazifop TM, Fluometuron TM, Fluorodifen TM, Ioxynil TM, Lenacil TM, Linuron TM, Mecoprop TM, Mefenacet TM, Metamitron TM, Metribuzin TM, Molinate TM, Monolinuron TM, MCPB TM, MCPA TM, MCPA thioethyl TM, Naproanilide TM, Naptalam TM, Nitralin TM, Nitrofen TM, Oxyfluorfen TM, Pendimethalin TM, Phenmedipham TM, Phenothiol TM, Picloram TM, Piperophos TM, Pretilachlor TM, Prometryn TM, Propachlor TM, Propanil TM, Pyrazolate TM, Pyrazoxyfen TM, SAP TM, Simazine TM, Simetryn TM, Swep TM, Trifluralin TM, TCA TM, and Terbacil TM.

15. The herbicidal composition according to any one of claims 12 to 14, wherein the 1,3-oxazin-4-one derivative has a concentration from 0.1 to 99% (w/w).

16. The herbicidal composition according to claim 15, wherein the 1,3-oxazin-4-one derivative has a concentration from 1 to 80% (w/w).

17. The herbicidal composition according to claim l6, in the form of a wettable powder, wherein the concentration is from 25 to 90% (w/w).

18. The herbicidal composition according to claim 16, in the form of a granule, wherein the concentration is from 1 to 35% (w/w).

19. The herbicidal composition according to claim 16, in the form of an emulsion concentrate, wherein the concentration is from 5 to 30% (w/w).

20. The herbicidal composition according to claim 16, in the form of a suspension concentrate, wherein the concentration is from 5 to 50% (w/w).

21. A method for controlling weeds at a locus, which method comprises applying to a place in need of weed control an effective amount of a composition as defined in any one of claims 12 to 20.

22. The method for controlling the growth of weed at a locus, which method comprises applying to the locus a composition according to any one of claims 12 to 20, wherein the 1,3-oxazin-4-one derivative is applied at a rate of 1 to 5000 g/ha.

23. The method according to claim 21 or 22, wherein the locus is planted or going to be planted with rice.