JPH05170763A - 2-substituted oxetane derivative - Google Patents

Abstract

PURPOSE:To obtain a new compound having excellent antifungal activity and agricultural germicidal activity. CONSTITUTION:A compound expressed by formula I [R<1> to R<4> and R<8> are H or lower alkyl; R<2> and R<3> together form cyclopentane or cyclohexane ring; R<5> to R<7> are H, halogen or (halogen-substituted)lower alkoxy; R<9> is heterocyclic ring containing 1-3 N atoms, (except 1H-1,2,4-triazole), etc.], e.g. (2R*, 3S*, 4R*)-2-(4-chlorophenyl)-3,4-dimethyl-2-[(1-pyrazolyl)methyl] oxetane. Furthermore, the compound expressed by formula I is obtained by reacting a compound expressed by formula II (Y is halogen, etc.) with a compound expressed by formula III in the presence of a base such as sodium carbonate in a solvent such as hexane.

Description

Detailed Description of the Invention

[0001]

OBJECT OF THE INVENTION It is an object of the present invention to provide a novel oxetane derivative having excellent antifungal activity and agricultural bactericidal activity and a method for producing the same.

[0002]

TECHNICAL FIELD The present invention relates to a novel oxetane derivative having excellent antifungal activity and agricultural fungicidal activity, and a method for producing the same.

[0003]

2. Description of the Related Art Although various triazole compounds having fungicidal activity and antifungal activity for agriculture are known, compounds having a heterocyclic group other than triazole ring and having an oxetane ring have not been known so far.

[0004]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention As a result of years of intensive research on the synthesis of a derivative having a heterocyclic skeleton other than the triazole ring and its physiological activity, the present inventors have found that
The present invention was completed by finding that a novel nitrogen-containing heterocyclic compound having an oxetane skeleton has excellent agricultural bactericidal activity and antifungal activity.

[0005]

[Constitution of the invention]

[0006]

The present invention comprises a novel oxetane derivative or a salt thereof, a method for producing them, and agricultural fungicides and antifungal agents containing them as active ingredients.

More specifically, a compound in which the 2-position of the oxetane ring is substituted with a lower alkyl group to which a 5- to 6-membered heterocyclic group containing 1 to 3 nitrogen atoms is bonded, a salt thereof, a process for producing them, and a method for producing them It consists of agricultural fungicides and antifungal agents as active ingredients.

More specifically, the present invention relates to the general formula (I)

[0009]

[Chemical 4]

[Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁸
Are the same or different and each represents a hydrogen atom or a lower alkyl group, and R ² and R ³ may be taken together to form a cyclopentane ring or a cyclohexane ring together with the carbon atom to which they are bonded, R ⁵ , R ⁶ And R ⁷ are the same or different,
A hydrogen atom, a halogen atom, a lower alkyl group optionally substituted with a halogen atom or a lower alkoxy group optionally substituted with a halogen atom is shown, and R ⁹ is 5 to 6 containing 1 to 3 nitrogen atoms. Membered heterocyclic group (however, 1H
-1,2,4-triazole group is excluded, and the heterocyclic group is 1
To 3 or more same or different halogen atoms, lower alkyl groups and lower alkoxy groups may be substituted. ) Is shown. ] The compound and its salt represented by the general formula (I
I)

[0011]

[Chemical 5]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ⁶ , R ⁷ and R ⁸ have the same meanings as described above, and Y represents a halogen atom, a lower alkylsulfonyloxy group or an arylsulfonyloxy group. ] The compound represented by
General formula (III)

[0013]

Embedded image R ⁹ H [wherein, R ⁹ is as defined above. ] A compound represented by the formula or a salt thereof is reacted in the presence or absence of a base to prepare a compound represented by the general formula (I), and a compound represented by the general formula (I) is effective. It comprises an agricultural fungicide composition and an antibacterial composition contained as components.

In the above, R ¹ , R ² , R ³ , R ⁴ ,
“Lower alkyl” in the definition of R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ includes, for example, methyl, ethyl, n-propyl,
Isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methyl Pentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2 -A linear or branched alkyl group having 1 to 6 carbon atoms such as ethylbutyl, preferably a linear or branched alkyl group having 1 to 4 carbon atoms.

In the above, R ⁵ , R ⁶ , R ⁷ and R ⁹
The "lower alkoxy" in the definition of means a group in which the above "lower alkyl" is bonded to an oxygen atom.

In the above, "lower alkyl optionally substituted by a halogen atom" in the definition of R ⁵ , R ⁶ and R ⁷ means that the "lower alkyl" is substituted with 1 to 3 of the "halogen atom". A group such as fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, iodomethyl, fluoroethyl, difluoroethyl, trifluoroethyl, chloroethyl, dichloroethyl, trichloroethyl. And preferably a methyl group substituted with 1 to 3 fluorine atoms or chlorine atoms, such as fluoromethyl, trifluoromethyl and chloromethyl.

In the above, "lower alkoxy optionally substituted by halogen atom" in the definition of R ⁵ , R ⁶ and R ⁷ means that the above "lower alkyl optionally substituted by halogen atom" is an oxygen atom. It is a bonded group.

In the above, "halogen atom" in the definition of R ⁵ , R ⁶ , R ⁷ , R ⁹ and Y means a fluorine atom,
It represents a chlorine atom, a bromine atom or an iodine atom, preferably a fluorine atom or a chlorine atom.

In the above, the term "5- to 6-membered heterocyclic group containing 1 to 3 nitrogen atoms" in the definition of R ⁹ means
Aromatic heterocyclic groups such as pyrrolyl, azepinyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and pyrrolidinyl, pyrrolinyl, imidazolidinyl,
Corresponding to these groups, such as imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl,
It is a partially or completely reduced group, and preferably a 5-membered heterocyclic group containing 1 or 2 nitrogen atoms.

In the above, "lower alkylsulfonyloxy" in the definition of Y means the above "lower alkyl".
Is a group bonded to the sulfur atom of the SO ₂ O group.

In the above, "arylsulfonyloxy" in the definition of Y is a group in which "aryl" is bonded to the sulfur atom of SO ₂ O group, and in this case, "aryl".
And 5 to 14 carbon atoms such as phenyl, indenyl, naphthyl, phenanthrenyl and anthracenyl.
Aromatic hydrocarbon groups, preferably phenyl groups. In addition, "aryl" may be substituted with 1 to 3 of the same or different "halogen atom", "lower alkyl" and "lower alkoxy".

The compounds of the present invention are specifically illustrated below, but the present invention is not limited thereto.

In the table below, the symbols in the column R ⁹ are as shown below.

[0024]

[Chemical 7]

[0025]

[Table 1]

[0026]

[Chemical 8]

──────────────────────────────────── Compound number R ¹ R ² R ³ R ⁴ R ⁵ , R ⁶ , R ⁷ R ⁸ R ⁹ ───────────────────────────────────── 1-1 HHHH 4-Cl H a 1-2 Me HHH 4-Cl H a 1-3 Me Me HH 4-Cl H a 1-4 Me Et HH 4-Cl H a 1-5 Me H Me H 4-Cl H a 1-6 Me H Et H 4-Cl H a 1-7 Et Me HH 4-Cl H a 1-8 Et Et HH 4-Cl H a 1-9 Et HHH 4-Cl H a 1-10 HH Me H 4-Cl H a 1-11 HH Me Me 4-Cl H a 1-12 HH Me Et 4-Cl H a 1-13 HH Et H 4-Cl H a 1-14 HH Et Et 4-Cl H a 1 -15 Et H Me H 4-Cl H a 1-16 Et H Et H 4-Cl H a 1-17 Et H n-Pr H 4-Cl H a 1-18 Et H i-Pr H 4-Cl H a 1-19 n-Pr HHH 4-Cl H a 1-20 n-Pr H Me H 4-Cl H a 1-21 n-Pr H Et H 4-Cl H a 1-22 n-Pr H n- Pr H 4-Cl H a 1-23 n-Pr H i -Pr H 4-Cl H a 1-24 i-Pr HHH 4-Cl H a 1-25 i-Pr H Me H 4-Cl H a 1-26 i-Pr H Et H 4-Cl H a 1- 27 i-Pr H n-Pr H 4-Cl H a 1-28 i-Pr H i-Pr H 4-Cl H a 1-29 HHHH 4-Cl H b 1-30 Me HHH 4-Cl H b 1 -31 Me Me HH 4-Cl Hb 1-32 Me Et HH 4-Cl Hb 1-33 Me H Me H 4-Cl Hb 1-34 Me H Et H 4-Cl Hb 1-35 Et Me HH 4-Cl Hb 1-36 Et Et HH 4-Cl Hb 1-37 Et HHH 4-Cl Hb 1-38 HH Me H 4-Cl H b 1-39 HH Me Me 4-Cl H b 1 -40 HH Me Et 4-Cl Hb 1-41 HH Et H 4-Cl H b 1-42 HH Et Et 4-Cl H b 1-43 Et H Me H 4-Cl H b 1-44 Et H Et H 4-Cl H b 1-45 Et H n-Pr H 4-Cl H b 1-46 Et H i-Pr H 4-Cl H b 1-47 n-Pr HHH 4-Cl H b 1-48 n -Pr H Me H 4-Cl Hb 1-49 n-Pr H Et H 4-Cl H b 1-50 n-Pr H n-Pr H 4-Cl H b 1-51 n-Pr H i-Pr H 4-Cl H b 1-52 i-Pr HHH 4-Cl H b 1-53 i-Pr H Me H 4-Cl H b 1-54 i-Pr H Et H 4-Cl H b 1-55 i-Pr H n-Pr H 4-Cl H b 1-56 i-Pr H i-Pr H 4-Cl H b 1-57 HHHH 4-Cl H c 1- 58 Me HHH 4-Cl H c 1-59 Me Me HH 4-Cl H c 1-60 Me Et HH 4-Cl H c 1-61 Me H Me H 4-Cl H c 1-62 Me H Et H 4 -Cl H c 1-63 Et Me HH 4-Cl H c 1-64 Et Et HH 4-Cl H c 1-65 Et HHH 4-Cl H c 1-66 HH Me H 4-Cl H c 1-67 HH Me Me 4-Cl H c 1-68 HH Me Et 4-Cl H c 1-69 HH Et H 4-Cl H c 1-70 HH Et Et 4-Cl H c 1-71 Et H Me H 4- Cl H c 1-72 Et H Et H 4-Cl H c 1-73 Et H n-Pr H 4-Cl H c 1-74 Et H i-Pr H 4-Cl H c 1-75 n-Pr HHH 4-Cl H c 1-76 n-Pr H Me H 4-Cl H c 1-77 n-Pr H Et H 4-Cl H c 1-78 n-Pr H n-Pr H 4-Cl H c 1 -79 n-Pr H i-Pr H 4-Cl H c 1-80 i-Pr HHH 4-Cl H c 1-81 i-Pr H Me H 4-Cl H c 1-82 i-Pr H Et H 4-Cl H c 1-83 i-Pr H n-Pr H 4-Cl H c 1-84 i-Pr H i-Pr H 4-Cl H c 1-85 H HHH 4-Cl H d 1-86 Me HHH 4-Cl H d 1-87 Me Me HH 4-Cl H d 1-88 Me Et HH 4-Cl H d 1-89 Me H Me H 4-Cl H d 1-90 Me H Et H 4-Cl H d 1-91 Et Me HH 4-Cl H d 1-92 Et Et HH 4-Cl H d 1-93 Et HHH 4-Cl H d 1-94 HH Me H 4-Cl H d 1-95 HH Me Me 4-Cl H d 1-96 HH Me Et 4-Cl H d 1-97 HH Et H 4-Cl H d 1-98 HH Et Et 4-Cl H d 1 -99 Et H Me H 4-Cl H d 1-100 Et H Et H 4-Cl H d 1-101 Et H n-Pr H 4-Cl H d 1-102 Et H i-Pr H 4-Cl H d 1-103 n-Pr HHH 4-Cl H d 1-104 n-Pr H Me H 4-Cl H d 1-105 n-Pr H Et H 4-Cl H d 1-106 n-Pr H n- Pr H 4-Cl H d 1-107 n-Pr H i-Pr H 4-Cl H d 1-108 i-Pr HHH 4-Cl H d 1-109 i-Pr H Me H 4-Cl H d 1 -110 i-Pr H Et H 4-Cl H d 1-111 i-Pr H n-Pr H 4-Cl H d 1-112 i-Pr H i-Pr H 4-Cl H e 1-113 HHHH 4 -Cl He 1-114 Me HHH 4-Cl He 1-11 Me Me HH 4-Cl H e 1-116 Me Et HH 4-Cl H e 1-117 Me H Me H 4-Cl H e 1-118 Me H Et H 4-Cl H e 1-119 Et Me HH 4 -Cl H e 1-120 Et Et HH 4-Cl H e 1-121 Et HHH 4-Cl H e 1-122 HH Me H 4-Cl H e 1-123 HH Me Me 4-Cl H e 1-124 HH Me Et 4-Cl H e 1-125 HH Et H 4-Cl H e 1-126 HH Et Et 4-Cl H e 1-127 Et H Me H 4-Cl H e 1-128 Et H Et H 4 -Cl He 1-129 Et H n-Pr H 4-Cl He 1-130 Et H i-Pr H 4-Cl He 1-131 n-Pr HHH 4-Cl He 1-132 n-Pr H Me H 4-Cl H e 1-133 n-Pr H Et H 4-Cl H e 1-134 n-Pr H n-Pr H 4-Cl H e 1-135 n-Pr H i-Pr H 4 -Cl H e 1-136 i-Pr HHH 4-Cl H e 1-137 i-Pr H Me H 4-Cl H e 1-138 i-Pr H Et H 4-Cl H e 1-139 i-Pr H n-Pr H 4-Cl H e 1-140 i-Pr H i-Pr H 4-Cl H e 1-141 HHHH 2,4-Cl ₂ H a 1-142 Me HHH 2,4-Cl ₂ H a 1-143 Me Me HH 2,4-Cl ₂ H a 1-144 Me Et HH 2,4-Cl ₂ H a 1-145 Me H Me H 2,4-Cl ₂ H a 1-146 Me H Et H 2,4-Cl ₂ H a 1-147 Et Me HH 2,4-Cl ₂ H a 1-148 Et Et HH 2,4-Cl ₂ H a 1-149 Et HHH 2,4-Cl ₂ H a 1-150 HH Me H 2,4-Cl ₂ H a 1-151 HH Me Me 2,4-Cl ₂ H a 1-152 HH Me Et 2,4-Cl ₂ H a 1-153 HH Et H 2,4-Cl ₂ H a 1-154 HH Et Et 2,4-Cl ₂ H a 1-155 Et H Me H 2,4-Cl ₂ H a 1-156 Et H Et H 2,4-Cl ₂ H a 1-157 Et H n -Pr H 2,4-Cl ₂ H a 1-158 Et H i-Pr H 2,4-Cl ₂ H a 1-159 n-Pr HHH 2,4-Cl ₂ H a 1-160 n-Pr H Me H 2,4-Cl ₂ H a 1-161 n-Pr H Et H 2,4-Cl ₂ H a 1-162 n-Pr H n-Pr H 2,4-Cl ₂ H a 1-163 n -Pr H i-Pr H 2,4-Cl ₂ H a 1-164 i-Pr HHH 2,4-Cl ₂ H a 1-165 i-Pr H Me H 2,4-Cl ₂ H a 1-166 i-Pr H Et H 2,4-Cl ₂ H a 1-167 i-Pr H n-Pr H 2,4-Cl ₂ H a 1-168 i-Pr H i-Pr H 2,4-Cl ₂ H a 1-169 HHHH 2,4-Cl ₂ H d 1-170 Me HHH 2,4-Cl ₂ H d 1-171 Me Me HH 2,4-Cl ₂ H d 1-172 Me Et HH 2,4 -Cl ₂ H d 1-173 Me H Me H 2,4-Cl ₂ H d 1-174 Me H Et H 2,4-Cl ₂ H d 1-175 Et Me HH 2,4-Cl ₂ H d 1 -176 Et Et HH 2,4-Cl ₂ H d 1-177 Et HHH 2,4-Cl ₂ H d 1-178 HH Me H 2,4-Cl ₂ H d 1-179 HH Me Me 2,4- Cl ₂ H d 1-180 HH Me Et 2,4-Cl ₂ H d 1-181 HH Et H 2,4-Cl ₂ H d 1-182 HH Et Et 2,4-Cl ₂ H d 1-183 Et H Me H 2,4-Cl ₂ H d 1-184 Et H Et H 2,4-Cl ₂ H d 1-185 Et H n-Pr H 2,4-Cl ₂ H d 1-186 Et H i- Pr H 2,4-Cl ₂ H d 1-187 n-Pr HHH 2,4-Cl ₂ H d 1-188 n-Pr H Me H 2,4-Cl ₂ H d 1-189 n-Pr H Et H 2,4-Cl ₂ H d 1-190 n-Pr H n-Pr H 2,4-Cl ₂ H d 1-191 n-Pr H i-Pr H 2,4-Cl ₂ H d 1-192 i-Pr HHH 2,4-Cl ₂ H d 1-193 i-Pr H Me H 2,4-Cl ₂ H d 1-194 i-Pr H Et H 2,4-Cl ₂ H d 1-195 i-Pr H n-Pr H 2,4-Cl ₂ H d 1-196 i-Pr H i-Pr H 2,4-Cl ₂ H d 1-197 HHHH 4-FH a 1-198 Me HHH 4-FH a 1-199 Me Me HH 4-FH a 1-200 Me Et HH 4-FH a 1-201 Me H Me H 4-FH a 1-202 Me H Et H 4-FH a 1-203 Et Me HH 4-FH a 1-204 Et Et HH 4-FH a 1-205 Et HHH 4-FH a 1-206 HH Me H 4-FH a 1-207 HH Me Me 4-FH a 1-208 HH Me Et 4-FH a 1-209 HH Et H 4-FH a 1-210 HH Et Et 4-FH a 1-211 Et H Me H 4-FH a 1-212 Et H Et H 4-FH a 1-213 Et H n-Pr H 4-FH a 1-214 Et H i-Pr H 4-FH a 1-215 n-Pr HHH 4-FH a 1-216 n-Pr H Me H 4-FH a 1-217 n-Pr H Et H 4-FH a 1-218 n-Pr H n-Pr H 4-FH a 1-219 n-Pr H i-Pr H 4-FH a 1-220 i-Pr HHH 4-FH a 1-221 i-Pr H Me H 4-FH a 1-222 i-Pr H Et H 4-FH a 1-223 i-Pr H n-Pr H 4- FH a 1- 24 i-Pr H i-Pr H 4-FH a 1-225 HHHH 4-FH d 1-226 Me HHH 4-FH d 1-227 Me Me HH 4-FH d 1-228 Me Et HH 4-FH d 1-229 Me H Me H 4-FH d 1-230 Me H Et H 4-FH d 1-231 Et Me HH 4-FH d 1-232 Et Et HH 4-FH d 1-233 Et HHH 4-FH d 1-234 HH Me H 4-FH d 1-235 HH Me Me 4-FH d 1-236 HH Me Et 4-FH d 1-237 HH Et H 4-FH d 1-238 HH Et Et 4-FH d 1-239 Et H Me H 4-FH d 1-240 Et H Et H 4-FH d 1-241 Et H n-Pr H 4-FH d 1-242 Et H i-Pr H 4-FH d 1 -243 n-Pr HHH 4-FH d 1-244 n-Pr H Me H 4-FH d 1-245 n-Pr H Et H 4-FH d 1-246 n-Pr H n-Pr H 4-FH d 1-247 n-Pr H i-Pr H 4-FH d 1-248 i-Pr HHH 4-FH d 1-249 i-Pr H Me H 4-FH d 1-250 i-Pr H Et H 4 -FH d 1-251 i-Pr H n-Pr H 4-FH d 1-252 i-Pr H i-Pr H 4-FH d 1-253 HHHH 4-FH a 1-254 Me HHH 2,4-F ₂ H a 1-255 Me Me HH 2,4-F ₂ H a 1-256 Me Et HH 2,4-F ₂ H a 1-257 Me H Me H 2,4-F ₂ H a 1-258 Me H Et H 2,4-F ₂ H a 1-259 Et Me HH 2,4-F ₂ H a 1-260 Et Et HH 2,4-F ₂ H a 1-261 Et HHH 2,4-F ₂ H a 1-262 HH Me H 2,4-F ₂ H a 1-263 HH Me Me 2,4-F ₂ H a 1-264 HH Me Et 2,4-F ₂ H a 1-265 HH Et H 2,4-F ₂ H a 1-266 HH Et Et 2,4-F ₂ H a 1-267 Et H Me H 2,4-F ₂ H a 1-268 Et H Et H 2,4-F ₂ H a 1-269 Et H n-Pr H 2,4-F ₂ H a 1-270 Et H i-Pr H 2,4-F ₂ H a 1-271 n-Pr HHH 2,4-F ₂ H a 1-272 n-Pr H Me H 2,4-F ₂ H a 1-273 n-Pr H Et H 2,4-F ₂ H a 1-274 n-Pr H n -Pr H 2,4-F ₂ H a 1-275 n-Pr H i-Pr H 2,4-F ₂ H a 1-276 i-Pr HHH 2,4-F ₂ H a 1-277 i- Pr H Me H 2,4-F ₂ H a 1-278 i-Pr H Et H 2,4-F ₂ H a 1-279 i-Pr H n-Pr H 2,4-F ₂ H a 1- 280 i-Pr H i-Pr H 2,4-F ₂ H a 1-281 HHHH 2,4-F ₂ H d 1-282 Me HHH 2,4-F ₂ H d 1-283 Me Me HH 2,4-F ₂ H d 1-284 Me Et HH 2,4-F ₂ H d 1-285 Me H Me H 2,4-F ₂ H d 1-286 Me H Et H 2,4-F ₂ H d 1-287 Et Me HH 2,4-F ₂ H d 1-288 Et Et HH 2,4-F ₂ H d 1-289 Et HHH 2,4-F ₂ H d 1-290 HH Me H 2,4-F ₂ H d 1-291 HH Me Me 2,4-F ₂ H d 1-292 HH Me Et 2,4-F ₂ H d 1-293 HH Et H 2,4-F ₂ H d 1-294 HH Et Et 2, 4-F ₂ H d 1-295 Et H Me H 2,4-F ₂ H d 1-296 Et H Et H 2,4-F ₂ H d 1-297 Et H n-Pr H 2,4-F ₂ H d 1-298 Et H i-Pr H 2,4-F ₂ H d 1-299 n-Pr HHH 2,4-F ₂ H d 1-300 n-Pr H Me H 2,4-F ₂ H d 1-301 n-Pr H Et H 2,4-F ₂ H d 1-302 n-Pr H n-Pr H 2,4-F ₂ H d 1-303 n-Pr H i-Pr H 2 , 4-F ₂ H d 1-304 i-Pr HHH 2,4-F ₂ H d 1-305 i-Pr H Me H 2,4-F ₂ H d 1-306 i-Pr H Et H 2, 4-F ₂ H d 1-307 i-Pr H n-Pr H 2,4-F ₂ H d 1-308 i-Pr H i-Pr H 2,4-F ₂ H d 1-309 HHHH 4-CF ₃ H a 1-310 Me HHH 4-CF ₃ H a 1-311 Me Me HH 4-CF ₃ H a 1-312 Me Et HH 4-CF ₃ H a 1-313 Me H Me H 4-CF ₃ H a 1- 314 Me H Et H 4-CF ₃ H a 1-315 Et Me HH 4-CF ₃ H a 1-316 Et Et HH 4-CF ₃ H a 1-317 Et HHH 4-CF ₃ H a 1-318 HH Me H 4-CF ₃ H a 1-319 HH Me Me 4-CF ₃ H a 1-320 HH Me Et 4-CF ₃ H a 1-321 HH Et H 4-CF ₃ H a 1-322 HH Et Et 4-CF ₃ H a 1-323 Et H Me H 4-CF ₃ H a 1-324 Et H Et H 4-CF ₃ H a 1-325 Et H n-Pr H 4-CF ₃ H a 1-326 Et H i-Pr H 4-CF ₃ H a 1-327 n-Pr HHH 4-CF ₃ H a 1-328 n-Pr H Me H 4-CF ₃ H a 1-329 n-Pr H Et H 4 -CF ₃ H a 1-330 n-Pr H n-Pr H 4-CF ₃ H a 1-331 n-Pr H i-Pr H 4-CF ₃ H a 1-332 i-Pr HHH 4-CF ₃ H a 1-333 i-Pr H Me H 4-CF ₃ H a 1-334 i-Pr H Et H 4-CF ₃ H a 1-335 i-Pr H n-Pr H 4-CF ₃ H a 1-336 i-Pr H i-Pr H 4-CF ₃ H a 1-337 HHHH 4-CF ₃ H d 1-338 Me HHH 4-CF ₃ H d 1-339 Me Me HH 4-CF ₃ H d 1-340 Me Et HH 4-CF ₃ H d 1-341 Me H Me H 4-CF ₃ H d 1-342 Me H Et H 4-CF ₃ H d 1-343 Et Me HH 4-CF ₃ H d 1-344 Et Et HH 4-CF ₃ H d 1-345 Et HHH 4-CF ₃ H d 1-346 HH Me H 4-CF ₃ H d 1-347 HH Me Me 4-CF ₃ H d 1-348 HH Me Et 4-CF ₃ H d 1-349 HH Et H 4-CF ₃ H d 1-350 HH Et Et 4-CF ₃ H d 1-351 Et H Me H 4-CF ₃ H d 1-352 Et H Et H 4-CF ₃ H d 1-353 Et H n -Pr H 4-CF ₃ H d 1-354 Et H i-Pr H 4-CF ₃ H d 1-355 n-Pr HHH 4-CF ₃ H d 1-356 n-Pr H Me H 4-CF ₃ H d 1-357 n-Pr H Et H 4-CF ₃ H d 1-358 n-Pr H n-Pr H 4-CF ₃ H d 1-359 n-Pr H i-Pr H 4-CF ₃ H d 1-360 i-Pr HHH 4-C F ₃ H d 1-361 i-Pr H Me H 4-CF ₃ H d 1-362 i-Pr H Et H 4-CF ₃ H d 1-363 i-Pr H n-Pr H 4-CF ₃ H d 1-364 i-Pr H i-Pr H 4-CF ₃ H d 1-365 HHHH 4-OCF ₃ H a 1-366 Me HHH 4-OCF ₃ H a 1-367 Me Me HH 4-OCF ₃ H a 1-368 Me Et HH 4-OCF ₃ H a 1-369 Me H Me H 4-OCF ₃ H a 1-370 Me H Et H 4-OCF ₃ H a 1-371 Et Me HH 4-OCF ₃ H a 1-372 Et Et HH 4-OCF ₃ H a 1-373 Et HHH 4-OCF ₃ H a 1-374 HH Me H 4-OCF ₃ H a 1-375 HH Me Me 4-OCF ₃ H a 1- 376 HH Me Et 4-OCF ₃ H a 1-377 HH Et H 4-OCF ₃ H a 1-378 HH Et Et 4-OCF ₃ H a 1-379 Et H Me H 4-OCF ₃ H a 1-380 Et H Et H 4-OCF ₃ H a 1-381 Et H n-Pr H 4-OCF ₃ H a 1-382 Et H i-Pr H 4-OCF ₃ H a 1-383 n-Pr HHH 4-OCF ₃ H a 1-384 n-Pr H Me H 4-OCF ₃ H a 1-385 n-Pr H Et H 4-OCF ₃ H a 1-386 n-Pr H n-Pr H 4-OCF ₃ H a 1- 87 n-Pr H i-Pr H 4-OCF 3 H a 1-388 i-Pr HHH 4-OCF 3 H a 1-389 i-Pr H Me H 4-OCF 3 H a 1-390 i-Pr H Et H 4-OCF ₃ H a 1-391 i-Pr H n-Pr H 4-OCF ₃ H a 1-392 i-Pr H i-Pr H 4-OCF ₃ H a 1-393 HHHH 4-OCF ₃ H d 1-394 Me HHH 4-OCF ₃ H d 1-395 Me Me HH 4-OCF ₃ H d 1-396 Me Et HH 4-OCF ₃ H d 1-397 Me H Me H 4-OCF ₃ H d 1-398 Me H Et H 4-OCF ₃ H d 1-399 Et Me HH 4-OCF ₃ H d 1-400 Et Et HH 4-OCF ₃ H d 1-401 Et HHH 4-OCF ₃ H d 1- 402 HH Me H 4-OCF ₃ H d 1-403 HH Me Me 4-OCF ₃ H d 1-404 HH Me Et 4-OCF ₃ H d 1-405 HH Et H 4-OCF ₃ H d 1-406 HH Et Et 4-OCF ₃ H d 1-407 Et H Me H 4-OCF ₃ H d 1-408 Et H Et H 4-OCF ₃ H d 1-409 Et H n-Pr H 4-OCF ₃ H d 1 -410 Et H i-Pr H 4-OCF ₃ H d 1-411 n-Pr HHH 4-OCF ₃ H d 1-412 n-Pr H Me H 4-OCF ₃ H d 1-413 n-Pr H Et H 4-OCF ₃ H d 1-414 n-Pr H n-Pr H 4-OCF ₃ H d 1-415 n-Pr H i-Pr H 4-OCF ₃ H d 1-416 i-Pr HHH 2,4-F ₂ H d 1-417 i-Pr H Me H 4-OCF ₃ H d 1-418 i-Pr H Et H 4-CF ₃ H d 1-419 i-Pr H n-Pr H 4 -Cl H d 1-420 i-Pr H i-Pr H 2,4-Cl ₂ H d 1-421 HHHHHH a 1-422 Me HHHHH a 1-423 Me Me HHHH a 1-424 Me Et HHHH a 1- 425 Me H Me HHH a 1-426 Me H Et HHH a 1-427 Et Me HHHH a 1-428 Et Et HHHH a 1-429 Et HHHHH a 1-430 HH Me HHH a-431 HH Me Me HH a 1 -432 HH Me Et HH a 1-433 HH Et HHH a 1-434 HH Et Et HH a 1-435 Et H Me HHa a-436 Et H Et HHH a 1-437 Et H n-Pr HHH a 1- 438 Et H i-Pr HHH a 1-439 n-Pr HHHHH a 1-440 n-Pr H Me HHH a 1-441 n-Pr H Et HHH a 1-442 n-Pr H n-Pr HHH a 1- 443 n-Pr H i-Pr HHH a 1-44 i-Pr HHHHH a 1-445 i-Pr H Me HHH a 1-446 i-Pr H Et HHH a 1-447 i-Pr H n-Pr HHH a 1-448 i-Pr H i-Pr HHH a 1 -449 HHHHHH d 1-450 Me HHHHH d
1-451 Me Me HHHH d 1-452 Me Et HHHH d 1-453 Me H Me HHH d 1-445 Me H Et HHH d 1-455 Et Me HHHH d 1-456 Et Et HHHH d 1-457 Et HHHHH d 1-458 HH Me HHH d 1-459 HH Me Me HH d 1-460 HH Me Et HH d 1-461 HH Et HHH d 1-462 HH Et Et HH d 1-463 Et H Me HHH d 1-464 Et H Et HHH d 1-465 Et H n-Pr HHH d 1-466 Et H i-Pr HHH d 1-467 n-Pr HHHHH d 1-468 n-Pr H Me HHH d 1-469 n-Pr H Et HHH d 1-470 n-Pr H n-Pr HHH d 1-471 n-Pr H i-Pr HHH d 1-472 i-Pr HHHHH d 1-473 i-Pr H Me HHH d 1-474 i-Pr H Et HHH d 1-475 i-Pr H n-Pr HHH d 1-476 i-Pr H i-Pr HHH d 1-477 Me Me Me Me 4-Cl H a 1-478 Me Me Me Me 2,4 -Cl ₂ H a 1-479 Me Me Me Me 4-FH a 1-480 Me Me Me Me 2,4-F ₂ H a 1-481 Me Me Me Me 2-Cl, 4-FH a 1-48 2 Me Me Me Me 4-Cl, 2-FH a 1-483 Me Me Me Me 4-CF ₃ H a 1-484 Me Me Me Me 4-OCF ₃ H a 1-485 Me Me Me Me HH a 1- 486 Me Me Me Me 4-CH ₃ H a 1-487 Me Me Me Me 4-OCH ₃ H a 1-488 Me Me Me Me 4-Cl H d 1-489 Me Me Me Me 2,4-Cl ₂ H d 1-490 Me Me Me Me 4-FH d 1-491 Me Me Me Me 2,4-F ₂ H d 1-492 Me Me Me Me 2-Cl, 4-FH d 1-493 Me Me Me Me 4 -Cl, 2-FH d 1-494 Me Me Me Me 4-CF ₃ H d 1-495 Me Me Me Me 4-OCF ₃ H d 1-496 Me Me Me Me HH d 1-497 Me Me Me Me 4 -CH ₃ H d 1-498 Me Me Me Me 4-OCH ₃ H d 1-499 Me Me Me Me 4-Cl He e 1-500 Me Me Me Me 2,4-Cl _{2 He} 1-501 Me Me Me Me 4-FH e 1-502 Me Me Me Me 2,4-F ₂ H e 1-503 Me Me Me Me 2-Cl, 4-FH e 1-504 Me Me Me Me 4-Cl, 2-FH e 1-505 Me Me Me Me 4-CF ₃ H e 1-506 Me Me Me Me 4-OCF ₃ H e 1-507 Me Me Me Me HH e 1-50 8 Me Me Me Me 4-CH ₃ H e 1-509 Me Me Me Me 4-OCH ₃ H e ─────────────────────────── ──────────

[0028]

[Table 2]

[0029]

[Chemical 9]

──────────────────────────────────── Compound number R ¹ R ⁴ n R ⁵ , R ⁶ , R ⁷ R ⁹ ──────────────────────────────────── 2-1 HH 3 4-Cl a 2-2 Me H 3 4-Cl a 2-3 Me Me 3 4-Cl a 2-4 H Me 3 4-Cl a 2-5 HH 4 4-Cl a 2-6 Me H 4 4-Cl a 2-7 Me Me 4 4-Cl a 2-8 H Me 4 4-Cl a 2-9 HH 3 2,4-Cl ₂ a 2-10 Me H 3 2,4-Cl ₂ a 2-11 Me Me 3 2,4-Cl ₂ a 2-12 H Me 3 2,4-Cl ₂ a 2-13 HH 4 2,4-Cl ₂ a 2-14 Me H 4 2,4-Cl ₂ a 2-15 Me Me 4 2,4-Cl ₂ a 2-16 H Me 4 2,4-Cl ₂ a 2-17 HH 3 4-F a 2-18 Me H 3 4-F a 2-19 Me Me 3 4-F a 2-20 H Me 3 4-F a 2-21 HH 4 4-F a 2-22 Me H 4 4-F a 2-23 Me Me 4 4-F a 2-24 H Me 4 4-F a 2-25 HH 3 2,4-F ₂ a 2-26 Me H 3 2,4-F ₂ a 2-27 Me Me 3 2,4-F ₂ a 2 -28 H Me 3 2,4-F ₂ a 2-29 HH 4 2,4-F ₂ a 2-30 Me H 4 2,4-F ₂ a 2-31 Me Me 4 2,4-F ₂ a 2-32 H Me 4 2,4-F ₂ a 2-33 HH 3 4-CF ₃ a 2-34 Me H 3 4-CF ₃ a 2-35 Me Me 3 4-CF ₃ a 2-36 H Me 3 4-CF ₃ a 2-37 HH 4 4-CF ₃ a 2-38 Me H 4 4-CF ₃ a 2-39 Me Me 4 4-CF ₃ a 2-40 H Me 4 4-CF ₃ a 2 -41 HH 3 4-OCF ₃ a 2-42 Me H 3 4-OCF ₃ a 2-43 Me Me 3 4-OCF ₃ a 2-44 H Me 3 4-OCF ₃ a 2-45 HH 4 4-OCF ₃ a 2-46 Me H 4 4-OCF ₃ a 2-47 Me Me 4 4-OCF ₃ a 2-48 H Me 4 4-OCF ₃ a 2-49 HH 3 4-Cl d 2-50 Me H 3 4-Cl d 2-51 Me Me 3 4-Cl d 2-52 H Me 3 4-Cl d 2-53 HH 4 4-Cl d 2-54 Me H 4 4-Cl d 2-55 Me Me 4 4-Cl d 2-56 H Me 4 4-Cl d 2-57 HH 3 2,4-Cl ₂ d 2-58 Me H 3 2,4-Cl _{2 d 2-59 Me Me 3 2,4-} Cl 2 d 2-60 H Me 3 2,4-Cl 2 d 2-61 HH 4 2,4-Cl 2 d 2-62 Me H 4 2,4- Cl ₂ d 2-63 Me Me 4 2,4-Cl ₂ d 2-64 H Me 4 2,4-Cl ₂ d 2-65 HH 3 4-F d 2-66 Me H 3 4-F d 2- 67 Me Me 3 4-F d 2-68 H Me 3 4-F d 2-69 HH 4 4-F d 2-70 Me H 4 4-F d 2-71 Me Me 4 4-F d 2-72 H Me 4 4-F d 2-73 HH 3 2,4-F ₂ d 2-74 Me H 3 2,4-F ₂ d 2-75 Me Me 3 2,4-F ₂ d 2-76 H Me 3 2,4-F ₂ d 2-77 HH 4 2,4-F ₂ d 2-78 Me H 4 2,4-F ₂ d 2-79 Me Me 4 2,4-F ₂ d 2-80 H Me 4 2,4-F ₂ d 2-81 HH 3 4-CF ₃ d 2-82 Me H 3 4-CF ₃ d 2-83 Me Me 3 4-CF ₃ d 2-84 H Me 3 4-CF ₃ d _{-85 HH 4 4-CF 3 d} 2-86 Me H 4 4-CF 3 d 2-87 Me Me 4 4-CF 3 d 2-88 H Me 4 4-CF 3 d 2-89 HH 3 4-OCF ₃ d 2-90 Me H 3 4-OCF ₃ d 2-91 Me Me 3 4-OCF ₃ d 2-92 H Me 3 4-OCF ₃ d 2-93 HH 4 4-OCF ₃ d 2-94 Me H 4 4-OCF ₃ d 2-95 Me Me 4 4-OCF ₃ d 2-96 H Me 4 4-OCF ₃ d ────────────────────── ────────────── The methods for producing the compounds of the present invention and intermediates thereof are shown below.

(Method A)

[0032]

[Chemical 10]

The carbonyl compound (AI) and the olefin compound (AII) are subjected to a photoreaction in the presence of a solvent to produce an oxetane compound (AIII) (a compound in which Y is a chlorine atom in the general formula (II)). It is a process.

The reaction was carried out by Sato and Tamura, tetrahedron.
Letters, Vol. 25, pp. 1821 to 1824 (1
984) (T. Sato, K. Tamura Tetrahedron Letters,
Vol. 25, 1821-1824 (1984)).

There is an optimum wavelength for this reaction.

The wavelength of the optimum light for irradiation varies depending on the carbonyl compound and the olefin compound as the raw materials, but the light source is not limited as long as it contains light of about 280-600 nm, but is preferably 300 to 400 nm. And more preferably around 350 nm. When a wavelength of 280 nm or less is included, it is preferably removed by using a filter or the like.

This step is carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction, and for example, benzene, toluene, xylene,
Aromatic hydrocarbons such as chlorobenzene, nitriles such as acetonitrile and benzonitrile, alcohols such as methanol, ethanol and i-propanol, ethers such as ether and tetrahydrofuran, lower aliphatic carbonization such as hexane, pentane and cyclohexane. Aromatic hydrocarbons (especially benzene, toluene, chlorobenzene) which function as a filter while being a solvent in order to prevent transmission of light having a wavelength of 285 nm or less are preferably used. A mixed solvent thereof is used.

The filter for preventing the light of 285 nm or less from passing therethrough is not particularly limited, but examples thereof include Pyrex glass, a glass filter for cutting a specific wavelength, a resin filter, and a fluorescent dye. When using these filters,
As described above, it is not always necessary to use benzene, toluene, chlorobenzene, etc. as long as the solvent dissolves the raw materials.

The reaction temperature is not particularly limited and is preferably -2.
It is carried out at 0 ° C. to 80 ° C., more preferably 10 ° C. to 40 ° C.

The reaction time mainly depends on the reaction temperature, the starting compound,
The time is usually from 1 hour to 4 days, preferably from 2 hours to 2 days, though it varies depending on the irradiation light and the type of solvent used.

In step A-2, chloro compound (AIII) to azole compound (AIV) (compound of general formula (I))
Is a step of manufacturing.

The reaction is carried out by reacting 1 equivalent or more of an azole compound (compound of general formula (III)) in the presence of 1 equivalent or more of a base in a solvent,
Alternatively, it is a method for producing the compound of the present invention by reacting a base salt of an azole.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but preferably it is an aliphatic carbonization such as hexane, heptane, ligroin or petroleum ether. Hydrogen; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane , Ethers such as dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin Octanol, cyclohexanol, methyl cellosolve, alcohols such as;
Nitro compounds such as nitroethane and nitrobenzene; Nitriles such as acetonitrile and isobutyronitrile; Formamide, dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide, 1,
Amides such as 3-dimethyl-2-imidazolidinone; sulfoxides such as dimethyl sulfoxide and sulfolane, more preferably formamide, dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide, 1,3- Amides such as dimethyl-2-imidazolidinone.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate and carbonic acid are preferred. Alkali metal hydrogen carbonate such as potassium hydrogen; Alkali metal hydride such as lithium hydride, sodium hydride, potassium hydride; Sodium hydroxide, potassium hydroxide,
Alkali metal hydroxides such as barium hydroxide; sodium methoxide, sodium ethoxide, bota-t
-Alkali metal alkoxides such as butoxide, triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-
Dimethylamino) pyridine, N, N-dimethylaniline, N,
N-diethylaniline, 1,5-diazabicyclo [4.3.0] nona
-5-Ene, 1,4-diazabicyclo [2.2.2] octane (DABC
O), 1,8-diazabicyclo [5.4.0] undec-7-ene (DB
U) or organic metal bases such as butyllithium or lithium diisopropylamide,
More preferred are alkali metal carbonates such as sodium carbonate and potassium carbonate.

In order to effectively carry out the reaction, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
It is also possible to add alkaline earth metal halides such as sodium iodide, sodium bromide, lithium bromide, crown ethers such as dibenzo-18-crown-6-, and the like.

The reaction temperature is -78 ° C to 200 ° C, preferably -20 ° C to 150 ° C.

The reaction time varies depending mainly on the reaction temperature, the starting compound or the type of solvent used, but is usually 1 hour to 24 hours, and preferably 2 hours to 10 hours.

(Method B)

[0049]

[Chemical 11]

Step B-1 is a carbonyl compound (BI)
And a olefin compound (VI) are subjected to a photoreaction to stereoselectively produce an oxetane compound (BIII).

This process is performed by T. Oppenlaender and P. Scho
enholzer, Helvetica Chimica Acta, Vol.72, 1972 (198
It can be performed according to the method described in 9).

R is preferably, for example, an alkyl group branched at the 1-position such as isopropyl group, s-butyl group and s-hexyl group, and the above "aryl group" such as benzhydryl group. 2 or 3 substituted methyl group, or (-)-menthyl group, (+)-menthyl group, 8-phenylmenthyl group, (-)-2-phenylcyclohexyl group, (+)-2-phenylcyclohexyl group, 2-hydroxycyclohexyl group, 2-acetoxycyclohexyl group, 2-methoxyethoxycyclohexyl group, 2-
Substitute a hydroxyl group protected by an alkyl group, a phenyl group, an aralkyl group, a hydroxyl group or a hydroxyl group-protecting group at the 2-position of the "cyclohexyl group" such as (t-butyldimethylsilyloxy) cyclohexyl group and 2-benzylcyclohexyl group. It is a cyclohexyl group having a group, and more preferably a cyclohexyl group having a hydroxyl group protected by an alkyl group, a phenyl group, an aralkyl group, a hydroxyl group or a hydroxyl-protecting group at the 2-position as a substituent.

The wavelength of the optimum light to be irradiated varies depending on the carbonyl compound and the olefin compound as the raw materials, but the light source is not limited as long as it contains light of about 280 to 600 nm, but it is preferably 300 to 400 nm. And more preferably around 350 nm. When a wavelength of 280 nm or less is included, it is preferably removed by using a filter or the like.

This step is carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction, and for example, benzene, toluene, xylene,
Aromatic hydrocarbons such as chlorobenzene, nitriles such as acetonitrile and benzonitrile, alcohols such as methanol, ethanol and i-propanol, ethers such as ether and tetrahydrofuran, lower aliphatic carbonization such as hexane, pentane and cyclohexane. Aromatic hydrocarbons (especially benzene, toluene, chlorobenzene) which function as a filter while being a solvent in order to prevent transmission of light having a wavelength of 285 nm or less are preferably used. A mixed solvent thereof is used.

The filter for preventing the light of 285 nm or less from passing therethrough is not particularly limited, and examples thereof include Pyrex glass, a glass filter for cutting a specific wavelength, a resin filter, and a fluorescent dye. When using these filters,
As described above, it is not always necessary to use benzene, toluene, chlorobenzene, etc. as long as the solvent dissolves the raw materials.

The reaction temperature is not particularly limited and is preferably -2.
It is carried out at 0 ° C. to 80 ° C., more preferably 10 ° C. to 40 ° C.

The reaction time mainly depends on the reaction temperature, the starting compound,
The time is usually from 1 hour to 4 days, preferably from 2 hours to 2 days, though it varies depending on the irradiation light and the type of solvent used.

Step B-2 is a step of reducing the ester group of (BIII) to produce an alcohol compound (BIV).

This step can be carried out by using a general ester reduction method, for example, the method described in New Experimental Chemistry Course (edited by the Chemical Society of Japan), Volume 15, Oxidation and Reduction [II]. The reducing agent is preferably a borohydride compound such as lithium aluminum hydride, sodium borohydride-lithium chloride or lithium borohydride.

The solvent used is not particularly limited as long as it does not inhibit the reaction, but ethers such as tetrahydrofuran and ethylene glycol dimethyl ether are preferred.

The reaction time varies depending on the reagents used, temperature, etc., but is usually 30 minutes to 5 hours, and preferably 1
Hours to 3 hours.

In step B-3, the alcohol compound (BI
In this step, the unprotected hydroxyl group of V) is converted into a nucleophilic leaving group Y to produce compound (BV).

For example, when Y is a halogen atom, it is carried out by using what is generally regarded as a halogenating reagent, and preferably thionyl halides such as thionyl chloride, thionyl bromide and thionyl iodide. , Sulfonyl halides such as sulfonyl chloride and sulfonyl bromide, phosphorus trihalides such as phosphorus trichloride and phosphorus tribromide, pentahalogenations such as phosphorus pentachloride, phosphorus pentabromide and phosphorus pentaiodide Phosphorus or phosphorus oxyhalide such as phosphorus oxychloride or phosphorus oxybromide is used, preferably phosphorus oxyhalide or thionyl halide is used.

When Y is a sulfonyl group, for example, a compound having the general formula R'SO ₂ -O-SO ₂ R'with compound (III) in the presence of a base or in the presence of a day in an inert solvent. (In the formula, R ′ represents a lower alkyl group such as methyl and ethyl; a halogen lower alkyl group such as trifluoromethyl and pentafluoroethyl; an aryl group such as benzene and p-toluene.) Or a formula R ′ SO ₂ −
It is achieved by reacting a compound having Z (in the formula, R ³ has the same meaning as described above, and Z represents a halogen atom such as a chlorine atom, a bromine atom or an iodine atom).

The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent, but preferably, aromatic hydrocarbons such as benzene, toluene and xylene. Halogenated hydrocarbons such as methylene chloride and chloroform; Esters such as ethyl acetate and propyl acetate; Ethers such as ether, tetrahydrofuran, dioxane and dimethoxytan or dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide And more preferably aromatic hydrocarbons such as toluene or halogenated hydrocarbons such as methylene chloride.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably alkali metal hydrogen such as lithium hydride, sodium hydride and potassium hydride. Inorganic bases such as compounds: triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline, 1,
5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-diazabicyclo
[5.4.0] Organic bases such as undec-7-ene (DBU) or organic metal bases such as butyllithium and lithium diisopropylamide, more preferably pyridine,
Organic bases such as triethylamine.

The reaction temperature is from room temperature to 150 for halogenation.
The temperature is 80 ° C to 120 ° C, preferably 80 ° C to 120 ° C. The sulfonation is carried out at -20 ° C to 50 ° C,
The temperature is preferably -15 ° C to room temperature.

The reaction time varies depending mainly on the reaction temperature, the starting compound or the type of solvent used, but is usually 5 minutes to 10 hours, and preferably 10 minutes to 3 hours.

In step B-4, the nucleophilic leaving group Y of the compound (BV) is replaced with an azole to give a compound (BVI) of the present invention (a compound of the general formula (I) in which R ⁸ is a hydrogen atom). ) Is manufactured.

This step can be carried out according to the step A-2.

(C method)

[0072]

[Chemical 12]

Step C is a step for producing compound (CII) (compound of general formula (II)) from alcohol compound (CI) and can be carried out according to step B-3.

In the above method, the compound synthesized as a racemate is subjected to optical resolution by adding a known resolving reagent to the racemate, for example, an optically active acid such as camphorsulfonic acid to form a crystalline salt. By carrying out, only one optically active substance can be taken out.

Hereinafter, the present invention will be described more specifically with reference to examples.

The symbol "*" in the text indicates a racemate. That is,
The notation (2R ^* , 3S ^* ) means a 1: 1 mixture of isomers of (2R, 3S) and (2S, 3R), which is synonymous with (2S ^* , 3R ^* ). On the other hand, (2R
^* , 3R ^* ) means that (2R, 3R) and (2S,
3S) means a 1: 1 mixture of isomers of
It has the same meaning as (2S ^* , 3S ^* ).

The stereoscopic representations used in the present invention to indicate the structural formulas of compounds show relative stereoscopic configurations, and also include their racemates.

[0078]

[Effect] The compound of the present invention is used as an agricultural fungicide,
It has a curative and preventive effect against plant diseases without damaging the host plant.

That is, by using it as a spraying agent or a water surface application agent, it is possible to particularly strongly control rice blight, which is an important disease in rice cultivation.

By using as a soil treatment or seed treatment agent, beet caused by Rhizoctonia,
Especially effective against seedling wilt of various crops such as cotton and cucumber,
It is possible to effectively control soil-borne diseases such as white silkworm of eggplants and cucurbits and black blight of potatoes.

On the other hand, crops such as rice, tomato, potato, cotton, eggplant, cucumber, and kidney bean are not damaged by a practical dose.

Further, it can be effectively used as a fungicide in orchards, non-agricultural lands, forests and the like.

The compound of the present invention is mixed with a carrier and, if necessary, other auxiliary agents, and has a formulation form usually used as an agricultural fungicide, such as powder, coarse powder, fine granule, granule,
It is prepared and used as a wettable powder, a flowable agent, an emulsion, an aqueous solution, an aqueous solvent, an oil suspension and the like. Of course, the crude product can be used as an active ingredient by stopping the purification at any stage of the purification.

The carrier as used herein is mixed with an agricultural fungicide in order to facilitate the accessibility of the active ingredient compound to the site to be treated and to facilitate storage, transportation or handling of the active ingredient compound. Means a synthetic or natural inorganic or organic substance.

As a suitable solid carrier, clays represented by kaolinite group, montmorillonite group or attabargite group, talc, mica, pyrophyllite, pumice stone, permukilite, gypsum, calcium carbonate, dolomite, diatomaceous earth, magnesium lime, etc. , Apatite, zeolite,
Inorganic substances such as anhydrous silicic acid and synthetic calcium silicate, soybean powder,
Tobacco powder, walnut powder, wheat flour, wood powder, starch, vegetable organic substances such as crystalline cellulose, coumarone resin, petroleum resin, alkyd resin, polyvinyl chloride, polyalkylene glycol, ketone resin, ester gum, copal gum, dammal gum, etc. Examples thereof include synthetic or natural polymer compounds, waxes such as carnapa wax and beeswax, and urea.

Suitable liquid carriers include paraffin or naphthenic hydrocarbons such as kerosene, mineral oil, spindle oil and white oil, aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, cumene and methylnaphthalene, and tetrachloride. Carbon, chlorinated hydrocarbons such as chloroform, trichloroethylene, monochlorobenzene, o-chlorotoluene, dioxane, ethers such as tetrahydrofuran, acetone, methyl ethyl ketone,
Ketones such as diisobutyl ketone, cyclohexanone, acetophenone, and isophorone, ethyl acetate, amyl acetate, ethylene glycol acetate, diethylene glycol acetate, dibutyl maleate, esters such as diethyl succinate, methanol, n-hexanol, ethylene glycol, diethylene glycol, cyclo Examples thereof include alcohols such as hexanol and benzyl alcohol, ether alcohols such as ethylene glycol ethyl ether, ethylene glycol phenyl ether, diethylene glycol ethyl ether and diethylene glycol butyl ether, polar solvents such as dimethylformamide and dimethyl sulfoxide, and water.

Surfactants used for the purposes of emulsification, dispersion, wetting, spreading, binding, disintegration control, active ingredient stabilization, fluidity improvement, rust prevention, etc. are nonionic, anionic, cationic. Both ionic and zwitterionic compounds can be used, but usually nonionic and / or anionic compounds are used.

Suitable nonionic surfactants include, for example, those obtained by polymerizing and adding ethylene oxide to higher alcohols such as lauryl alcohol, stearyl alcohol and oleyl alcohol, and those obtained by polymerizing and adding ethylene oxide to alkylphenols such as isooctylphenol and nonylphenol. , Butylnaphthol, octylnaphthol, and other alkylnaphthols with ethylene oxide polymerized, palmitic acid, stearic acid, oleic acid, and other higher fatty acids with ethylene oxide polymerized, stearic acid, dilaurylphosphoric acid, etc. Alternatively, a polymer obtained by polymerizing addition of ethylene oxide to a dialkyl phosphoric acid, a polymer obtained by polymerizing addition of ethylene oxide to an amine such as dodecylamine or stearic acid amide, or sorbitan That the higher fatty acid ester and ethylene oxide to that of the alcohol was polymerized addition,
Examples thereof include those obtained by polymerizing addition of ethylene oxide and propylene oxide. Suitable anionic surfactants include, for example, sodium lauric sulfate, alkyl sulfate salts such as oleyl alcohol sulfate amine salt, sulfosuccinic acid dioctyl ester sodium,
Examples thereof include alkylsulfonates such as sodium 2-ethylhexenesulfonate, sodium isopropylnaphthalenesulfonate, sodium methylenebisnaphthalenesulfonate, sodium ligninsulfonate, and arylsulfonates such as sodium dodecylbenzenesulfonate.

Furthermore, in order to improve the properties of the preparation and enhance the biological effect, the agricultural fungicide of the present invention includes casein, gelatin, albumin, glue, sodium alginate, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol and the like. It is also possible to use the high molecular compound and other auxiliaries.

The above-mentioned carrier and various auxiliary agents are appropriately used alone or in combination depending on the purpose, taking into consideration the dosage form of the preparation, the application scene and the like.

The powder is, for example, usually an active ingredient compound of
The content is 1 to 25 parts by weight, and the rest is a solid carrier.

As the wettable powder, for example, the active ingredient compound is usually used.
It is contained in an amount of 1 to 80 parts by weight, and the balance is a solid carrier and a dispersion wetting agent, and if necessary, a protective colloid agent, a thixotropic agent, an antifoaming agent and the like are added.

Granules are prepared, for example, by adding 1 of the active ingredient compound.
˜35 parts by weight, the balance mostly solid carrier.

When used, it is mixed with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers, soil conditioners, etc. to expand the range of application and save labor. It can also be achieved.

The treatment amount varies depending on the weather conditions, formulation form, treatment time, treatment method, place, target disease, target crop, etc., but usually 0.1 g per are are as an active ingredient.
To 100 g, preferably 5 g to 40 g,
Emulsions, wettable powders, suspensions and the like are usually prepared in a predetermined amount of 1 liter to 10 liters of water per areal (surfactant, polyoxyethylene resin acid, lignin sulfonate, abietic acid salt, if desired. , A spreading agent such as dinaphthylmethane disulfonate, or paraffin can be added.), And the granules and the like are usually treated without any dilution.

[0096]

[Test Examples] The effects of the compounds of the present invention will be specifically shown by the following test examples.

Test Example 1 Rice crest disease control test (therapeutic effect) 4-5 leaf stage rice seedlings (quality: Nipponbare) were cultivated with oat grains pre-cultured with Rhizoctonia solani. Four-
Five grains were placed and inoculated. After inoculation, the rice seedlings should be heated to 25-27
After being placed in a room at 0 ° C. and 100% relative humidity for 24 hours, a 10 ppm solution of the test compound was sprayed at a rate of 30 ml per 3 pots. Subsequently, the rice seedlings were placed in the same room for 5 days to cause disease, and the control efficacy was investigated based on the height of the lesion formed on the leaf sheath. The results are shown in Table 3.

The control efficacy (the same as in the following test examples) was expressed by the following criteria by visually observing the degree of disease of test plants.

5: No onset of disease was observed. 4: The degree of disease is 10% or less of the untreated group (the same applies to the case where the test compound is not tested). 3: The degree of disease is 10% or more and 30% or less of the untreated section. 2: The degree of disease is 30% or more and 50% or less of the untreated area. 1: The degree of disease is 50% or more and 70% or less of the untreated area. 0: The degree of disease was 70% or more of the untreated plot, showing no difference from the untreated plot.

The numbers of the compounds used in the test are the numbers of Examples described later.

Barley powdery mildew control test (therapeutic effect) Barley seedlings (cultivar: Akakami Riki) at 1 leaf stage were treated with barley powdery mildew.
(Erysiphe graminis f.sp.hordei) was sprinkled and inoculated. After inoculating the bacteria, the barley seedlings were placed in a glass greenhouse at a temperature of 15 to 20 ° C. for 24 hours, and then 3 ppm of the test compound
The solution was sprayed at a rate of 30 ml per 3 pots. continue,
Put barley seedlings in a glass greenhouse for 10 days to cause illness.
The control efficacy was investigated based on the area of lesions formed on the leaves. The results are shown in Table 3.

Test Example 3 Apple scab control test (preventive effect) 300 ppm of the test compound was added to apple seedlings at the 3-4 leaf stage.
The solution was sprayed at a rate of 30 ml per 3 pots. 24 hours after the application of the drug solution, a conidia suspension of apple scab (Venturia inaequalis) was spray-inoculated. After inoculation, the apple seedlings were placed in a room at a temperature of 20-22 ° C. and a relative humidity of 100% for 3 days, then placed in a glass room at 20-22 ° C. for 10 days to cause disease, and formed on the 3rd-4th leaves. The control efficacy was investigated based on the area of the lesion. The results are shown in Table 3.

Test Example 4 Rice blast control test (therapeutic effect) Rice blast fungus (Pyr) was added to rice seedlings (quality: Kofu) at the 4-5 leaf stage.
Conidia suspension of icularia oryzae) was spray-inoculated. After inoculating the bacteria, the rice seedlings were placed in a room at a temperature of 20 to 22 ° C and a relative humidity of 100% for 24 hours, and then a 10 ppm solution of the test compound was added to the solution.
Sprayed at a rate of 30 ml per pot.

Subsequently, the rice seedlings were placed in the same room for 6 days to cause disease, and the control efficacy was investigated based on the number of lesions formed on the upper 2 leaves. The results are shown in Table 3.

[0105]

[Table 3] In addition, in Table 3, "-" mark shows an untested.

[0106]

[Examples] The present invention will be specifically described below with reference to Examples, but the present invention is not limited thereto.

Example 1 (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4-dimethyl-2
-[(1-Pyrazolyl) methyl] oxetane (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4-dimethyl-2
-Methanesulfonyloxymethyl oxetane (500 mg,
1.64 mmol), pyrazole (238.3 mg, 3.50 mmol) and sodium iodide (212 mg, 1.41 mmol) in 1,3-dimethyl-2-imidazolidinone (30 ml) suspension at 60C at 0 ° C-sodium hydride (177 mg, 4.43 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes and 90 ° C. for 7 hours. After the temperature was lowered to room temperature, saturated aqueous sodium thiosulfate was added, and the mixture was extracted with ethyl acetate-hexane (2: 1 v / v). The extract layer was washed with water and dried over anhydrous magnesium sulfate. After concentration, the obtained residue was purified by silica gel column chromatography to obtain the target compound (271 mg, 0.979 mmol).

Yield 60%, melting point 64 ° C NMR spectrum (CDCl ₃ ) δppm: 0.61 (d, 3H, J = 7.5Hz), 1.0
7 (d, 3H, J = 6.5Hz), 3.14 (dq, 1H, J = 7.5Hz, J = 7.5Hz), 4.23
(d, 1H, J = 14.6Hz), 4.30 (dq, 1H, J = 7.5Hz, J = 6.5Hz), 4.58
(d, 1H, J = 14.6Hz), 6.21 (dd, 1H, J = 1.8Hz, J = 2.5Hz), 7.23
(d, 2H, J = 8.7Hz), 7.34 (d, 2H, J = 8.7Hz), 7.47 (d, 1H, J = 1.8H
z), 7.52 (d, 1H, J = 2.5Hz). Mass spectrum (m / z): 276 (M ⁺ ), 217,195,139,129,111. Example 2 (2R ^* , 3S ^* , 4R ^* )-2-[(4 -Chloropyrazol-1-yl) methyl)]-3,4-dimethyloxetane (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4-dimethyl-2
-Methanesulfonyloxymethyl oxetane (500 mg,
1.64 mmol), 4-chloropyrazole (252 mg, 2.46 mmol) and sodium iodide (212 mg, 1.41 mol) in 1,3-dimethyl-2
60% sodium hydride (177 mg, 4.43 mmol) was added at 0 ° C. to an imidazolidinone (30 ml) suspension. The reaction mixture was stirred at room temperature for 30 minutes and 90 ° C. for 3.5 hours. After the temperature was lowered to room temperature, saturated aqueous sodium thiosulfate was added, and the mixture was extracted with ethyl acetate-hexane (1: 1 v / v). The extract layer was washed with water and dried over anhydrous magnesium sulfate. After concentration, the obtained residue was purified by silica gel column chromatography to obtain the target compound (328 mg, 1.05 mmol).

Yield 64%, melting point 54 ° C NMR spectrum (CDCl ₃ ) δppm: 0.63 (d, 3H, J = 7.5Hz), 1.1
2 (d, 3H, J = 7.3Hz), 3.10 (dq, 1H, J = 7.5Hz, J = 7.5Hz), 4.19
(d, 1H, J = 14.6Hz), 4.21 (dq, 1H, J = 7.5Hz, J = 7.3Hz), 4.54
(d, 1H, J = 14.6Hz), 7.25 (d, 2H, J = 8.9Hz), 7.30 (d, 2H, J = 8.9
Hz), 7.39 (s, 1H), 7.57 (s, 1H) .Mass spectrum (m / z): 310 (M ⁺ ), 251,197,164,149,140,12
9,111,104,89,75,63,56,52. Example 3 (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4-dimethyl-2
-[(1,2,3-triazol-1-yl) methyloxetane
(a) and (2R ^* , 3S ^* , 4R ^* ) -2- (4-chlorophenyl) -3,4-
Dimethyl-2 [(1,2,3-triazol-2-yl) methyl] oxetane (b) (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4-dimethyl-2
-Methanesulfonyloxymethyl oxetane (500 mg,
1.64mmol), 1,2,3-triazole (0.2ml, 3.45mmol) and sodium iodide (212mg, 1.41mol) of 1,3-dimethyl-2
60% sodium hydride (177 mg, 4.43 mmol) was added at 0 ° C. to an imidazolidinone (30 ml) suspension. The reaction mixture was stirred at room temperature for 30 minutes and 90 ° C. for 6.5 hours. After the temperature was lowered to room temperature, saturated aqueous sodium thiosulfate was added, and the mixture was extracted with ethyl acetate-hexane (1: 1 v / v). The extract layer was washed with water and dried over anhydrous magnesium sulfate. After concentration, the obtained residue was purified by silica gel column chromatography to obtain a (high polarity 146 mg, 0.53 mmol) and b (low polarity 226 mg, 0.81 mmol).

(A) Highly polar compound: yield 32%, melting point 91-9
1.5 ° C NMR spectrum (CDCl ₃ ) δppm: 0.64 (d, 3H, J = 7.4Hz), 1.1
2 (d, 3H, J = 6.5Hz), 3.04 (dq, 1H, J = 7.4Hz, J = 7.4Hz), 4.38 (d
q, 1H, J = 7.4Hz, J = 6.5Hz), 4.49 (d, 1H, J = 12.0Hz,), 4.94
(d, 1H, J = 12.0Hz), 7.27 (d, 2H, J = 6.8Hz), 7.31 (d, 2H, J = 6.8
Hz), 7.65 (brs, 1H), 7.77 (brs, 1H) .Mass spectrum (m
/ z): 277 (M ⁺ ), 265,239,195,164,149,141,125,111,104,7
5,56,41. (B) Low-polarity compound: yield 49%, melting point 94 ° C NMR spectrum (CDCl ₃ ) δppm: 0.71 (d, 3H, J = 7.5Hz), 1.1
3 (d, 3H, J = 6.5Hz), 3.29 (dq, 1H, J = 7.5Hz, J = 7.5Hz), 4.47 (d
q, 1H, J = 7.5Hz, J = 6.5Hz), 4.76 (d, 1H, J = 14.2Hz,), 4.90
(d, 1H, J = 14.2Hz), 7.2 (d, 2H, J = 8.7Hz), 7.31 (d, 2H, J = 8.7H
z), 7.60 (s, 2H) .Mass spectrum (m / z): 278 (M + 1) ⁺ , 256,222,195,164,149,
141,129,111. Example 4 (2R ^* , 3S ^* , 4R ^* )-2- (4-chlorophenyl) -3,4dimethyl-2- (1-imidazolyl) methyloxetane (2R ^* , 3S ^* , 4R) -2- (4-chlorophenyl) -3,4 dimethyl-2-methanesulfonyloxymethyl oxetane (500 mg, 1.64 mmo
l), imidazole (238.2 mg, 3.50 mmo
l) and sodium iodide (212 mg, 1.41 mo)
l) 1,3-dimethyl-2-imidazolidinone (30
60% sodium hydride (17 ml) at 0 ° C.
7 mg, 4.43 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes and 90 ° C. for 3 hours. After the temperature was lowered to room temperature, saturated aqueous sodium thiosulfate was added, and the mixture was extracted with ethyl acetate-hexane (2: 1 v / v). The extract layer was washed with water and dried over anhydrous magnesium sulfate. After concentration, the obtained residue was purified by silica gel chromatography to obtain the desired product (217 mg, 0.784 mm
ol) was obtained.

Yield 48%. Melting point 76-77 ° C NMR spectrum (CDCl ₃ ) δppm: 0.72 (d, 3
H, J = 7.4 Hz), 1.18 (d, 3H, J = 6.
4 Hz), 2.98 (dd, 1H, J = 7.4, 7.4)
Hz), 4.22 (d, 1H, J = 14.5Hz),
4.47 (d, 1H, J = 14.5Hz), 4.66
(Dq, 1H, J = 7.4, 6.4 Hz), 6.99
(Brs, 1H), 7.01 (brs, 1H), 7.2
3 (d, 2H, J = 8.7 Hz), 7.34 (d, 2)
H, J = 8.7 Hz), 7.70 (brs, 1H). MS (m / z): 276 (M +), 217, 149, 1
39,129,111,105,97,82,69,5
7, 41.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hajime Ota 1041 Yasu, Yasu-cho, Yasu-gun, Shiga Sankyo Stock Company In-house

Claims (3)

[Claims] 1. A compound represented by the general formula (I): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁸ are the same or different and represent a hydrogen atom or a lower alkyl group, and R ² and R ^2
3 may together form a cyclopentane or cyclohexane ring with their attached carbon atoms,
R ⁵ , R ⁶ and R ⁷ are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group optionally substituted with a halogen atom or a lower alkoxy group optionally substituted with a halogen atom, and R ⁹ Is a 5- to 6-membered heterocyclic group containing 1 to 3 nitrogen atoms (excluding 1H-1,2,4-triazole group, and the heterocyclic group is 1 to 3 identical or different) Optionally substituted with a halogen atom, a lower alkyl group or a lower alkoxy group). ] The compound and its salt represented by these. 2. A compound represented by the general formula (II): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁸ are the same or different and represent a hydrogen atom or a lower alkyl group, and R ² and R ^2
3 may together form a cyclopentane or cyclohexane ring with their attached carbon atoms,
R ⁵ , R ⁶ and R ⁷ are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group optionally substituted by a halogen atom or a lower alkoxy group optionally substituted by a halogen atom, and Y is A halogen atom, a lower alkylsulfonyloxy group or an arylsulfonyloxy group is shown. R ⁹ is a 5- to 6-membered heterocyclic group containing 1 to 3 nitrogen atoms (provided that 1H-1,2,4-triazole group is excluded, and the heterocyclic group is 1 to 3 identical or Which may be substituted with different halogen atoms, lower alkyl groups or lower alkoxy groups). A compound represented by, general formula (III) ## STR3 ## in R ⁹ H [wherein, R ⁹ is a nitrogen atom 1 to 3 5 to 6-membered Hajime Tamaki containing (However, IH-1, Except for the 2,4-triazole group, the heterocyclic group may be substituted with 1 to 3 identical or different halogen atoms, lower alkyl groups and lower alkoxy groups.). ] The compound or its salt represented by these is reacted in the presence or absence of a base, The manufacturing method of the compound of Claim 1 characterized by the above-mentioned. 3. An agricultural fungicide composition and an antibacterial composition containing the compound according to claim 1 as an active ingredient.