WO2001016125A1 - 2-benzyloxy-7-oxabicyclo[4.1.0]heptane derivatives and herbicide containing the same - Google Patents

Abstract

2-benzyloxy-7-oxabicyclo[4.1.0]heptane derivatives represented by general formula (I), which have excellent herbicidal activity against weeds and excellent selectivity to crop plants; and a herbicide containing any of the derivatives as the active ingredient. In formula (I), R1 and R2 each is halogeno, alkyl, etc.; R3 is halogeno, alkyl, etc.; R4 is alkyl, etc.; R5 is alkyl, etc.; R6 is alkyl, etc.; R7 is acyl, an aromatic heterocyclic group, etc.; and p is an integer of 0 to 3.

Description

 Specification

2-benzyloxy-1 7-oxabicyclo [4.1.0] heptane derivative and herbicides containing it

 The present invention relates to a novel 2-benzyloxy-7-year-old xabicyclo [4.1.0] heptane derivative and a herbicide containing the same as an active ingredient. Background art

 2-benzyloxy-17-oxabicyclo [4.1.0] heptane derivatives having herbicidal activity are described in International Application WO 97/02258 and International Application WO 098/45235. However, the compounds of the present invention are not described in these documents.

 It is desirable that the herbicide used for useful crops be a drug that shows sufficient herbicidal effects at low doses and that exhibits selectivity between crops and weeds. Therefore, an object of the present invention is to provide a compound having excellent herbicidal activity and selectivity among crop weeds. Disclosure of the invention

 The present inventors have conducted various studies in view of such circumstances, and as a result, have found that the novel 2-benzyloxy-17-oxabicyclo [4.1.0] heptane derivative has excellent herbicidal activity and selectivity among crop weeds. We have found and completed the present invention.

 That is, the present invention relates to (1)

[I]

In the formula, and R ₂ are the same or different and are a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group, an alkoxycarbonyl group, an acyl group, a cyano group or Represents a two-terminal group,

R ₃ represents a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group or an alkoxy group, and p represents an integer of 0 to 3 (when p is an integer of 2 to 3, R ₃ is the same or different ,

R ₄ represents a hydrogen atom, an alkyl group or an alkoxy group,

R ₅ represents a hydrogen atom, an alkyl group or a benzyl group,

Re represents a hydrogen atom, an alkyl group, a benzyl group or an alkoxy group; R ₇ represents an acyl group, a cycloalkyl group, an isocyanate group, an aromatic heterocyclic group (wherein the group is selected from the group consisting of 1 It may be substituted by four identical or different substituents, such as a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, Alkoxy group, alkoxyalkoxy group, alkoxycarbonylalkoxy group, cyanoalkoxy group, rubamoylalkoxy group (the nitrogen atom of the group is the same or different and hydrogen atom or alkyl group is substituted), alkylthio group, alkylsulfonyl group , Acyl group, alkoxycarbonyl group, cyano group, carbamo (A nitrogen atom of the group is the same or different and a hydrogen atom or an alkyl group is substituted), a nitrogen group or an amino group (a nitrogen atom of the group is the same or different and a hydrogen atom, an alkyl group, an acyl group Is substituted with a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, an alkylsulfonyl group, a haloalkylsulfonyl group or a cycloalkylalkylsulfonyl group), and two lower alkoxy groups are bonded to each other to form a lower alkyl group. May form a dioxy group).

General formula, [II]

[Wherein, R ₈ represents a hydrogen atom, an alkyl group or an alkoxy group,

R ₉ represents a hydrogen atom or an alkyl group; R ₈ and R ₉ may form a carboxy group together with these bonded carbon atoms;

R ₁₀ is a cycloalkyl group, aromatic RRC group II heterocyclic group, aryl group (where aromatic

 81

The group heterocyclic group and aryl group may be substituted by 1 to 4 identical or different substituents selected from the following substituent groups.

Examples of the substituent group include a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, a haloalkoxy group, an alkoxyalkoxy group, an alkoxycarbonylalkoxy group, and a cyanoalkoxy. Group, carbamoylalkoxy group (the nitrogen atom of the group is the same or different and hydrogen atom or alkyl group is substituted), alkylthio group, alkylsulfonyl group, acryl group, alkoxycarbonyl group, cyano group, carbamoyl group ( The nitrogen atom of the group is the same or different and a hydrogen atom or an alkyl group is substituted), a nitro group or

Amino group (where the nitrogen atom of the group is the same or different and is replaced by a hydrogen atom, And two adjacent lower alkoxy groups may be bonded to each other to form a lower alkylenedioxy group. )] Or a general formula,

[III]

Wherein, R _u represents a hydrogen atom, an alkyl group, a cycloalkyl group, § alkenyl group, an alkynyl group, an alkoxyalkyl group, an alkyl thio al Kill group or an alkoxycarbonylalkyl group,

 Rl 2 is a hydrogen atom, an alkyl group, an acyl group, a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, a cycloalkylcarbonyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an alkylsulfonyl group , A nonalkylalkylsulfonyl group, a cycloalkylalkylsulfonyl group, a cycloalkylsulfonyl group, an optionally substituted benzylsulfonyl group, an optionally substituted phenylsulfonyl group, an alkoxycarbonyl group, an optionally substituted benzyloxycarbo Nitro group, phenyloxycarbonyl group, carbamoyl group which may be substituted (the same or different nitrogen atom as hydrogen atom, alkyl group, benzyl group which may be substituted or may be substituted Or a phenyl group is substituted) Yl group (in which the same or different and a hydrogen atom on a nitrogen atom, alkyl group, an optionally substituted benzyl group or optionally substituted phenyl group optionally is substituted) represents a. ] 2-benzyloxy 7-year-old xabicyclo [4.1.0] heptane derivative represented by I,

 (2) — a general synthetic formula [V], which is a novel synthetic intermediate for producing the compound represented by the general formula [I],

(In the formula, R ₁₃ represents an alkyl group or a benzyl group, Ri ₄ represents an alkyl group or an alkoxy group, and R _i5 has the same meaning as above except for a formyl group or an optionally substituted benzyl group. xenon emission derivatives cyclohexane represented by representative.) the R ₇ having the same meaning,

(3) New synthetic intermediate for producing the compound represented by the general formula [I] Is a general formula [VI]

(Wherein, R ₅ , R _6, and R ₇ each have the same meaning as described above.) A 7-oxabicyclo [4.1.0] heptane-1-one derivative represented by the formula:

 (4) General formula [VII] which is a novel synthetic intermediate for producing the compound represented by general formula [I]

(Wherein, R ₁₃ , R ₁₄ and R ₇ each have the same meaning as described above.)

 (5) General formula [VIII], which is a novel synthetic intermediate for producing the compound represented by general formula [I],

(Wherein, R ₁₃ , R ₆ and R ₇ have the same meanings as described above, respectively). 2-Hydroxy-7-oxabicyclo [4.1.0] heptane derivative

(6) General formula [IX], which is a novel synthetic intermediate for producing the compound represented by general formula [I],

(Wherein, R ₂ , Rs, R 4, Ri 3, R ₆ , R 7, and p each have the same meaning as described above), and (7) A 2_benzyloxy 7-oxabicyclo [4.1.0] heptane derivative represented by the formula [I] and a herbicide containing the same.

 The terms used in this specification are defined below.

 A halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

 The alkyl group means a linear or branched alkyl group having 1 to 6 carbon atoms, unless otherwise specified. Examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and an isobutyl group. , Sec-butyl group or tert-butyl group.

 The cycloalkyl group is a cycloalkyl group having 3 to 8 carbon atoms, and examples thereof include a propyl group, a pentyl group, and a hexyl group.

 A cycloalkyl group having 1 to 6 carbon atoms substituted with a cycloalkyl group having 3 to 8 carbon atoms includes, for example, a propylmethyl group, a cyclobutylmethyl group, and a cyclopentylmethyl group. Or a cyclohexylmethyl group.

 Unless otherwise specified, the alkenyl group means a linear or branched alkenyl group having 2 to 6 carbon atoms, for example, a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl 12-propininole, 2-methyl-11-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl or 2-pentenyl Can be.

An alkynyl group is a straight or branched chain having 2 to 6 carbon atoms unless otherwise specified. A branched alkynyl group, for example, an ethur group, a 1-propynyl group, a 2-propynyl group, a 1-methyl-2-propynyl group, a 2-butynyl group, a 3-butynyl group or a 2-pentynyl group. Can be.

 Unless otherwise specified, a haloalkyl group refers to a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms and substituted by the same or different halogen atoms 1 to 9; Examples thereof include a trifluoromethyl group and a tetrafluoroethyl group.

 The haloalkoxy group refers to a (haloalkyl) 10- group in which the haloalkyl moiety has the above-mentioned meaning, and examples thereof include a difluoromethoxy group, a trifluoromethoxy group, and a 2,2,2-trifluorofluorooxy group. Can be.

 An alkoxy group, an alkoxycarbonyl group, an alkoxycarbonylalkyl group, and an alkoxyalkyl group have the meanings described above in which the alkyl moiety is (alkyl) -0-, (alkyl) -10-CO-, and (alkyl) 1- O — CO— (C 1-6 alkylene), (alkyl) —0— (C 1-6 alkylene), for example, methoxy, ethoxy, methoxycarbonyl, ethoxycarponyl Isopropylcarbonyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxymethyl group or ethoxymethyl group.

 The alkoxyalkoxy group and the alkoxycarbonylalkoxy group mean a (alkoxy)-(alkoxy)-group or a (alkoxy) -CO- (alkoxy) group in which the alkoxy moiety has the above-mentioned meaning, for example, a methoxy methoxy group, Examples thereof include a ethoxy, xydimethoxy group or an ethoxycarbonylmethoxy group.

Alkylthio group, an alkylsulfonyl group, an alkyl thio alkyl Moto及beauty alkylsulfonyl group, the alkyl moiety is Ru meaning der of (alkyl) one S- group, (alkyl) Single S0 ₂ - group, (alkyl) Single S — (Carbon chain 1 to 6 alkylene) one group, (alkyl) one SO ₂ — (carbon chain 1 to 6 alkylene) One group, such as methylthio, ethylthio, methylsulfur Examples thereof include a honyl group, an ethylsulfonyl group, a methylthiomethyl group and a methylsulfonylmethyl group.

Cycloalkylalkylcarbonyl group, cycloalkylcarbonyl group. The cycloalkylalkylsulfonyl group and the cycloalkylsulfonyl group are those in which the cycloalkylalkyl moiety is as defined above, a (cycloalkylalkyl) -CO— group, a (cycloalkyl) — CO- group, (cycloalk Kiruarukiru) Single S0 ₂ - group, (cycloalkyl) Single SO ₂ - represents a group, for example consequent opening cyclopropylmethyl Cal Poni group, a cyclopropyl group, a cyclopropylmethyl sulfonyl group or a cyclopropyl sulfonyl group And the like.

 The haloalkylcarbonyl group and the haloalkylsulfonyl group represent a (haloalkyl) 1 CO— group and a (haloalkyl) 1 S02— group in which the noloalkyl moiety is as defined above, for example, a chloroacetyl group, a trifluoroacetyl group. Examples thereof include a cetyl group, a pentafluoropropionyl group, a chloromethanesulfonyl group, and a trifluoromethylsulfonyl group.

 A hydrogen atom or an alkyl group substituted with a hydrogen atom or an alkyl group that is the same or different from a cyanoalkoxy group or a nitrogen atom is a force group that has a hydrogen atom or an alkyl group that is the same or different from a cyano group or a nitrogen atom. The alkoxy moiety substituted by the group represents a group having the above-mentioned meaning, and examples thereof include a cyanomethoxy group and an N-methylcarbamoylmethoxy group.

 The term `` acyl group '' refers to a linear or branched aliphatic acetyl group having 1 to 6 carbon atoms, such as a formyl group, an acetyl group, a propionyl group, an isopropionyl group, a butyryl group or a bivaloyl group. Can be.

 A nitrogen atom substituted with the same or different hydrogen atom or an alkyl group is, for example, an N-methylcarbamoyl group or an N, N-dimethyl rubamoyl group.

A hydrogen atom or an alkyl group substituted on the nitrogen atom with the same or different hydrogen atom or an alkyl group means that the hydrogen atom and the alkoxy moiety are In the above meaning, it represents one group of (potamoyl)-(alkoxy), for example, an N-methylcarbamoylmethoxy group or an N, N-dimethylcarbamoylmethoxy group.

An optionally substituted benzyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an optionally substituted benzyloxy group, an optionally substituted phenoxy group, The optionally substituted phenyl group, the optionally substituted phenylsulfonyl group and the optionally substituted benzylsulfonyl group may be, for example, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl Group, alkylthioalkyl group, alkylsulfonylalkyl group, alkoxy group, alkoxyalkoxy group, alkoxycarbonylalkoxy group, cyanoalkoxy group, nitrogen atom substituted with the same or different hydrogen atom or alkyl group Moylalkoxy group, alkyl group, Rukylsulfonyl, acyl, alkoxycarbonyl, cyano, (the same or different hydrogen atom or alkyl group as the nitrogen atom) force rubamoyl group, nitro group or (the same or different hydrogen atom as the nitrogen atom) Atom, an alkyl group, an acyl group, a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, an alkylsulfonyl group, a haloalkylsulfonyl group or a cycloalkylalkylsulfonyl group) which may be substituted by a substituent such as an amino group. Is shown.

 The aryl group is a phenyl group.

The aromatic heterocyclic group is a 5- to 6-membered aromatic heterocyclic group having 1 to 2 'heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and is a furyl group. Thienyl group, pyrrolyl group, isoxazolyl group, oxazolyl group, isothiazolyl group, thiazolyl group, pyrazolyl group, imidazolinole group, pyridyl group, pyridazinyl group, pyrimidinyl group or virazinyl group. BEST MODE FOR CARRYING OUT THE INVENTION Next, typical specific examples of the compound of the present invention are shown in Tables 1 to 73. However, the compounds of the present invention are not limited to these compounds. The compound numbers will be referred to in the following description.

 The following notations in the table have the following meanings, respectively.

Me: methyl group

 E t: ethyl group

 P r: n-propyl group

 P r-i: isopropyl group

 B u: n-butyl group

 B u-i: isobutyl group

 B u— s: s e c.

 B u— t: t e r t. —Butyl group

 P en: n-pentyl group

 P r-c: cyclopropyl group

 P en — c: cyclopentyl group

H e X- c: cyclohexyl group

 M e 0: methoxy group

 P h: phenyl group

 B n: benzyl group

In addition, for example, PM4-C1) indicates a 4-chloroethyl group, and Bn (4-Cl)

4- represents a benzyl group.

Further, diastereomers 1 and 2 in the table are defined as 1 for the diastereomer compound eluting first in the Kawapage phase HPLC (developing solvent; n-hexane: ethyl acetate), and 2 for the diastereomer compound eluting later. It was described.

The compound of the present invention and the described compound have an asymmetric carbon atom and include all stereoisomers as the compound of the present invention, and include, for example, the following stereoisomers.

[HI]

 [J-I] PI]

SZT9l / lO OAV Rl3 Rl3

[V-a] [V-b]

^R 5,, ¾ R5,

^Ho ^ O R7

[Vir-a], ^Η ° ^ Ο [vir-ζb] Ό [vir-¾c] ₇ ^Ηα "'Ο [vi-ζdl

^H0 _

 [vm'-al [VIII'-bl [vm'-c] [vnr-dl

 [IX'-al Il '-bl Hata

4 ^l R ₇

[IX'-d [IX'-d]

9Z8S0 / 00df / X3d SZT9l / lO OAV

9Z8S0 / 00df / X3d SZT9l / lO

9Z8S0 / 00df / X3d SZT9l / lO OAV

9Z8S0 / 00df / X3d SZT9l / lO OAV

fc7: one 1> d

/ O ΪΪΟAV:

/ O ΪΪΟAV:

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,

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Compound

R ₁₄ Rl5 ^ -NMR δ value (ppm) Solvent (CDC1 TMS) number

 2-1 13 Me Me 6-MeO-3-pyridylmethyl

2-1 14 Me Me 4,6-Me ₂ -3-pyridylmethyl

 2-〗 L 15 Me Me 4-pyrimiainyl

 2-1 L 16 Me Me 4-pyrimidinylmethyl

2-1 L 17 Me Me 4,6-Me ₂ -2-pyrimidinyl

 2-1 118 Me Me 4-Cl-2-pyrimidinyl

 2-1 119 Me Me 4-MeO-2-pyrimidinyl

2-1 L20 Me Me 4,6-Me ₂ -2-pyrimiainylmethyl

 2-] L21 Me Me 4-Cl-2-pyrimidinylmethyl

 2-] L22 Me Me 4-MeO-2-pyrimidinylmethyl

 2-1 L23 Me Me 2-pyrazinylmethyl

2-] L24 Me Me 5,6-Me ₂ -2-pyrazinylmethyl

 2-] L25 Me Me 6-MeO- 2 -pyrazinylmethyl

2-1 126 Me Me 5,6-Me ₂ -2-pyrazinyl

 2-] L27 Me Me 6-MeO-2-pyrazinyl

 2-] L28 Me Me 4-pyridazinyl

 2-1 129 Me Me 6-Me-3-pyridazinyl

 2-1 L30 Me Me 6-MeO- 3-pyridazinyl

 2- 131 Me Me 6-Cl-3-pyridazinyl

 2-j 132 Me Me 3-pyridazinylmethyl

 2- 133 Me Me 4-pyridazinylmethyl

 2- L34 Me Me 6-Me- 3-pyridazinylmethyl

 2- L35 Me Me 6-MeO-3-pyridazinylmethyl

 2- L36 Me Me 6-Cl-3-pyridazinylmethyl

2- 137 Me Me 3,4-Me ₂ -l-pyrrolyl

_{2- 138 Me Me 3,4-Me 2} - 1-pyrrolylmethyl

 2- L39 Me Me 3-Me-1-pyrazolylmethyl

 2- L40 Me Me 3-Me-1-pyrazolyl

 2- 141 Me Me 3-Cl-l-pyrazolylmethyl

 2- 142 Me Me 3-Cl-l-pyrazolyl

 2- 143 Me Me 3-MeO- 1-pyrazolylmethyl

 2- 144 Me Me 3-MeO- 1-pyrazoly

 2- 145 Me Me 2-C 1 -imidazolylmethyl

 2-146 Me Me 4, 5-Me2-1-imidazolylmethyl;

 2- 147 Me Me 2-MeO- 1 -imidazolylmethyl

 2- 148 Me Me 1-imidazolylmethyl

 2- 149 Me Me 2-Cl-l-imidazolyl

 2- 150 Me Me 2-Me- l-imidazolyl

 2- 151 Me Me 2-MeO- l-imidazolyl

2- 152 Me Me 4,5-Me2- l-imidazolyl

Article 22

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9Z8S0 / 00df / X3d SZT91 / 10 O / SX

Fifteen Next, a general method for producing the compound of the present invention will be described. However, the method is not limited to these methods.

 <Production method 1>

 The compound [I] of the present invention can be produced, for example, by the following method (Scheme 1).

(Wherein, R ₂ , R ₃ , R ₄ , R ₅ , Re> R ₇ and p have the same meanings as above, and L is a leaving group, and is a halogen atom, a methanesulfonoxy group. Or an alkylsulfonyloxy group such as an ethanesulfonyloxy group, a benzenesulfonyloxy group, or p-toluenesulfur Represents an arylsulfonyloxy group which may be substituted, such as a phonyloxy group. )

 Scheme 1 shows three production routes starting from the <<, /?-Unsaturated cyclic ketone compound represented by the general formula [ν '].

 That is, the <<, —unsaturated cyclic ketone compound represented by the general formula [V] is reacted with an oxidizing agent in a solvent to produce a compound represented by the general formula [VI], and further reduced in the solvent. After reacting the compound with an agent to produce a cyclic alcohol compound represented by the general formula [VIII], the cyclic alcohol compound represented by the general formula [VIII] is finally dissolved in a solvent in the presence of a base to obtain a compound represented by the general formula [a]. The compound of the present invention represented by the general formula [I] can be obtained by reacting with a benzyl halide compound or a sulfonic acid ester compound of a benzyl alcohol.

Further, the «, -unsaturated cyclic ketone compound represented by the general formula [V] is reacted with a reducing agent in a solvent to produce an unsaturated alcohol compound represented by the general formula [νπ ']. To produce a cyclic alcohol compound represented by the general formula [VIII]. Finally, the cyclic alcohol compound represented by the general formula [VIII] is reacted in a solvent in the presence of a base with a compound represented by the general formula [ _a The compound of the present invention represented by the general formula [I] can be obtained by reacting the compound with a benzyl halide compound or a sulfonic ester compound of a benzyl alcohol.

In addition, the <<, /?-Unsaturated cyclic ketone compound represented by the general formula [V] is reacted with a reducing agent in a solvent to produce an unsaturated alcohol compound represented by the general formula [νπ '] And a benzyl halide compound or a benzyl alcohol sulfonic acid ester compound represented by the general formula [a] in the presence of a base in an unsaturated alcohol compound represented by the general formula [νπ '] in a solvent. To produce a benzyl ether compound represented by the general formula [IX]. Finally, the benzyl ether compound represented by the general formula [IX] is reacted with an oxidizing agent in a solvent to produce a compound represented by the general formula [I]. The compounds of the present invention represented can be obtained. If it becomes necessary to purify the compound of the present invention, it can be purified by any purification method such as recrystallization, column chromatography or liquid chromatography. Therefore, it can be separated and purified.

 From the compound represented by the general formula [V] to the compound represented by the general formula [VI], from the compound represented by the general formula [νπ '] to the compound represented by the general formula [VIII] or the general formula [IX] The compound of the present invention represented by the general formula [I] is produced from the compound represented by the general formula (I) in the presence or absence of a catalyst in a solvent, in the presence or absence of a base, at a reaction temperature of 0 to 120, The reaction with the oxidizing agent is preferably performed at 0 to 80 ° C for 10 minutes to 24 hours. The amount of the reagent used in the reaction is determined based on the amount of the oxidizing agent per 1 equivalent of the compound represented by the general formula [V], the compound represented by the general formula [νπ '] or the compound represented by the general formula [IX]. When 1 to 3 equivalents of a base are used, the base is 0.5 to 3 equivalents. Examples of the oxidizing agent include organic peroxides such as hydrogen peroxide, alkyl hydroperoxide or peracetic acid, and m-chloroperbenzoic acid. Examples of the catalyst include metal oxides such as vanadium oxide. Examples of the base include an inorganic base such as potassium carbonate, sodium hydroxide, or a hydroxide hydroxide. Examples of the solvent include halogenated hydrocarbons such as chloroform and carbon tetrachloride, alcohols such as methanol and ethanol, aromatic hydrocarbons such as benzene and toluene, water, acetic acid, and mixtures thereof. Can be

The production of the compound represented by the general formula [VIII] from the compound represented by the general formula [νπ '] or the compound represented by the general formula [VI] from the compound represented by the general formula [V] is usually performed. The reaction is carried out in a solvent at a reaction temperature of -70 to 12010, preferably at -40 to 80 for 10 minutes to 24 hours. The amount of the reagent used for the reaction is 1 to 3 equivalents of the reducing agent with respect to 1 equivalent of the compound represented by the general formula [V] or the compound represented by the general formula [VI]. Examples of the reducing agent include diborane, borane 'tetrahydrofuran complex, diisobutylaluminum hydride, sodium borohydride or L-selectride. Examples of the solvent include ethers such as getyl ether and tetrahydrofuran, alcohols such as methanol and ethanol, aromatic hydrocarbons such as benzene and toluene, water, and mixtures thereof. In this production method, (S) and (R) 2-methyl-CBS-oxabodin Reduction reaction with diborane in the presence of 1 to 50% molar equivalent of asymmetric catalyst (for example, see Journal "OB" The American "Chemical" Society, J. Am. Chem. Soc., 109, 5551 (1987)) In addition, in the presence of an optically active diamine, an asymmetric reduction reaction with hydrogen using a ruthenium catalyst (for example, the Journal of the American “Chemical” Society, J. Am. Chem. Soc.), 120 , 1086 (1998)), it is possible to selectively produce an alcohol having a desired configuration by subjecting it to various asymmetric reductions. The production of the compound of the present invention represented by the general formula [I] from the compound represented by the general formula [IX] from the compound represented by the general formula [νπ '] or the compound represented by the general formula [VIII] includes: In general, the reaction is carried out in a solvent in the presence of a base at a reaction temperature of 0 to 120 ° C, preferably 0 to 80 "for 10 minutes to 24 hours. 1 to 3 equivalents of the compound represented by the general formula [a] and 1 to 3 equivalents of the base per 1 equivalent of the compound represented by the general formula [VIII]. Inorganic bases such as lithium, sodium hydride, sodium hydroxide and carbonated carbonate; metal salts of alcohols such as sodium ethoxide, sodium methoxide and potassium tert-butoxide; 1,8-diazabicyclo [ 5.4.0] —Organic bases such as 7-indene. For example, ethers such as getyl ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and carbon tetrachloride, amides such as Ν, Ν-dimethylformamide, dimethyl sulfoxide, sulfolane, etc. Examples include sulfur compounds, aromatic hydrocarbons such as benzene and toluene, ketones such as acetone, acetonitril, water, and mixtures thereof.

<Synthesis of <<,; 3-Unsaturated cyclic ketone compound represented by general formula [V]>

 [b] [V]

 (Scheme 2)

(Wherein, R ₅ , R ₆ and R ₇ each have the same meaning as described above.)

That is, the _α , 9-unsaturated cyclic ketone compound represented by the general formula [V] is represented by the aldehyde represented by the general formula [b] and the general formula [c] as shown in Scheme 2. The alkyl vinyl ketone can be produced according to a known method (for example, The Journal of Organic Chemistry) (J. Org. Chem.) 45, 5399 (1980) Organic Synthesis ( Org. Synth), 61, 129 (1986)).

The aldehyde represented by the general formula [b] is a Heck reaction between a corresponding halide derivative and an aryl alcohol derivative (for example, The Journal of Ob-Organic 'Chemistry (J. Org. Chem.), 41, 1206 (1976); see Tetrahedron, 35, 329 (1979)), the ring-opening reaction of the corresponding oxilane derivative in the presence of an acid catalyst (eg, The Journal. Chem.), 62, 6547 (1997); Synthetic Communications (Synth. Comm.), 25, 2695 (1995)), and the corresponding chemistries. (See, for example, Tetrahedron Lett., 21, 3535 (1980)), the reduction and oxidation of the corresponding carboxylic acid ester (for example, Journal of the -Chemical 'Society 1 Perkin Trans 1 (J. Chem. So c. See Perkin Trans. 1), 41 (1990)) or a known method such as formylation.

 (Scheme 3) [V-2]

(In the formula, R ₅ , R _s and R ₁₀ each have the same meaning as described above.)

 In addition, as shown in Scheme 3, a reaction between a "-formylcarboxylic acid derivative represented by the general formula [d] and an alkyl vinyl ketone represented by the general formula [c] (for example, Chemisin 'Berrichete) Ber.), 98, 1399 (1965)) can be used to produce a compound of the formula [V-2] wherein R is an acyl group.

Manufacturing method 2>

 The compound [1-3] of the present invention can be produced as follows.

(Wherein, R ₂ , R ₃ , R ₄ , R ₅ , R ₆ and p each have the same meaning as described above, and R ₁₅ represents an alkyl group.) The compound [1-3] of the present invention is produced by reacting the compound [1-1], which can be produced by the above-mentioned production method 1, in a solvent mixed with water in the presence of a base, followed by neutralization. [1-2] in a solvent in the presence of a base in the presence of a diphenylphosphoric acid azide. In the production of compound [1-2] from compound [1-1], the reaction is usually carried out at a reaction temperature of 0 to 120 ° (preferably 0 to 80) for 10 minutes to 24 hours. The amount of the base is 1 to 20 equivalents with respect to 1 equivalent of the compound [1-1] As the base, for example, an inorganic base such as sodium hydroxide, lithium hydroxide, lithium carbonate or the like Examples of the solvent mixed with water include alcohols such as methanol and ethanol, ethers such as dimethyl ether and tetrahydrofuran, amides such as Ν, Ν-dimethylformamide, dimethyl sulfoxide, and sulfolane. And the like, aromatic hydrocarbons such as benzene and toluene, ketones such as acetone, acetonitrile, water and mixtures thereof.

The production of compound [G3] from compound [1-2] is usually carried out at a reaction temperature of 0 to 150, preferably 0 to 0.120, for 10 minutes to 24 hours. The amount of the reagent used in the reaction is 1 to 2 equivalents of diphenylphosphoric acid azide and 1 to 3 equivalents of the base per 1 equivalent of compound [1-2]. Examples of the base include inorganic bases such as hydrogenated sodium, hydrogenated sodium, sodium hydroxide and carbonated carbonate, and metal salts of alcohols such as sodium ethoxide, sodium methoxide, and potassium tert-butoxide. And organic bases such as pyridine, triethylamine, 1,8-diazabicyclo [5.4.0] -17-indene. Examples of the solvent include alcohols such as methanol, ethanol, and tert-butanol; ethers such as getyl ether and tetrahydrofuran; halogenated hydrocarbons such as chloroform and carbon tetrachloride; Examples thereof include amides such as N-dimethylformamide, sulfur compounds such as dimethylsulfoxide and sulfolane, aromatic hydrocarbons such as benzene and toluene, ketones such as acetone, acetonitrile, and mixtures thereof. Manufacturing method 3> The compound [1-4] of the present invention can be produced as follows.

(Wherein, Ri, R ₂ , R ₃ , R ₄ , R ₅ , R _6, and p each have the same meaning as described above.) The compound of the present invention [1-4] is obtained by the method 1 or the method It can be produced by reacting the compound [III] produced in 2 with sodium borohydride in a solvent.

The compound [1-4] is usually produced at a reaction temperature of 20 to 120, preferably 0 to 80, for 10 minutes to 24 hours. The amount of the reagent used for the reaction is 0.5 to 3 equivalents of sodium borohydride per 1 equivalent of the compound [3]. As the solvent, for example, those similar to the production of compound [1-3] from compound [I · ² ] of production method 2 can be mentioned.

<Production method 4>

 The compound [Γ5] of the present invention can be produced as follows.

(Wherein 1 ^, R ₂ , R ₃ , R ₄ , R ₅ , R ₆ and p each have the same meaning as described above. R ₁₆ represents an alkyl group, a cycloalkylalkyl group, an aryl group, a propargyl group, an alkoxyalkyl group, an alkylthio group; an alkyl group or an alkoxycarbonylalkyl group; L represents a leaving group; Alkylsulfonyloxy group such as methanesulfonyloxy group or ethanesulfonyloxy group, or benzenesulfonyloxy group or p-toluenesulfonyloxy group; Represents a sulfonyloxy group. )

 Compound [1-5] of the present invention is produced by reacting compound [1-4] which can be produced by the above-mentioned production method 1 or 3 with compound [e] in a solvent in the presence of a base. be able to.

 In the production of compound [G5], the reaction is usually carried out at a reaction temperature of 0 to: 120 ° (preferably at 0 to 80) for 10 minutes to 24 hours.

 [1-4] One equivalent of compound [e] or base is desirable per equivalent, but can be arbitrarily changed according to the reaction situation. Examples of the base include inorganic bases such as potassium carbonate, sodium hydroxide, sodium hydride, and sodium hydride; alkali metal alkoxides such as sodium ethoxide and sodium methoxide; and 1,8-diazabicyclo [ 5.4.0] — 7— Organic bases such as pendene. Examples of the solvent include halogenated hydrocarbons such as porcine, ethers such as dimethyl ether and tetrahydrofuran, aromatic hydrocarbons such as benzene and toluene, and aliphatic hydrocarbons such as hexane and heptane. , Ketones such as acetone and methyl isobutyl ketone, esters such as ethyl acetate, amides such as N-methylpyrrolidone, N, N-dimethylformamide, sulfur compounds such as dimethyl sulfoxide and sulfolane, and acetonitrile Or mixtures thereof o

 <Production method 5>

The compound [1-7] of the present invention can be produced as follows.

_{(Wherein, Ri, R 2, R 3} , R 4, R 5, R 6, R u and p are each as meaning as defined above.)

 The compound [1-7] of the present invention is obtained by hydrolyzing the compound [1-6] which can be produced by the above-mentioned production method 1, the above production method 3 or the above production method 4 in a solvent in the presence of an acid or a base. Can be manufactured.

 The compound [1-7] is usually produced at a reaction temperature of 0 to 120, preferably at 0 to 80 ° C for 10 minutes to 24 hours. The amount of reagent used in the reaction depends on the compound

 [1-6] 1 to 20 equivalents of acid or base per 1 equivalent. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide and carbonate carbonate. Examples of the acid include hydrochloric acid, hydrobromic acid or sulfuric acid. Examples of the solvent to be mixed with water include alcohols such as methanol and ethanol, ethers such as getyl ether and tetrahydrofuran, amides such as N, N-dimethylformamide, dimethyl sulfoxide, and dimethyl sulfoxide. Examples thereof include sulfur compounds such as ruphorane, aromatic hydrocarbons such as benzene and toluene, ketones such as acetone, acetonitrile, and mixtures thereof.

 <Production method 6>

 The compound [1-8] of the present invention can be produced as follows.

(Wherein, R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , and p each have the same meaning as described above, Y represents a halogen atom, Ri ₇ represents an alkyl group, an acyl group, or a phenol group. Alkylcarbonyl group, cycloalkylalkylcarbonyl group, cycloalkylcarbonyl group, optionally substituted benzylcarbonyl group, optionally substituted benzoyl group, alkylsulfonyl group, haloalkylsulfonyl group, cycloalkylalkylsulfonyl group , Cycloalkylsulfonyl group, optionally substituted benzylsulfonyl group, optionally substituted phenylsulfonyl group, alkoxycarbonyl group, optionally substituted benzyloxycarbonyl group or optionally substituted phenoxycarbo R ₁₈ represents R ₁₇ other than an alkyl group.)

Compound [1-8] of the present invention is obtained by reacting compound [1-7] which can be produced by the above-mentioned production method 1 or the above-mentioned production method 5 with compound [f] or compound [ _g ] in a solvent in the presence of a base. It can be manufactured by

 In the production of compound [1-8], the reaction is carried out usually at a reaction temperature of 0 to 120 t, preferably at 0 to 80 for 10 minutes to 24 hours. The amount of reagent used in the reaction depends on the compound

[1-8] The compound [f] or the compound [ _g ] is 1-2 equivalents and 1-2 equivalents of a base per 1 equivalent. Examples of the base include those similar to the production of compound [1-3] from compound [1-2] in production method 2. As the solvent, for example, those similar to the production method 4 can be mentioned.

<Production method 7>

 The compound [1-9] of the present invention can be produced as follows.

(In the formula, R ₂ , R ₃ , R ₄ , R ₅ , Re, Rii, Y and p each have the same meaning as described above, and R ₁₉ and R ₂₀ are the same or different, and may be an alkyl group or substituted. Represents a good benzyl group or a phenyl group which may be substituted, and W represents an oxygen atom or a zeo atom.)

 The compound [1-9] of the present invention is obtained by reacting the compound [1-7] and the compound [h] or the compound [r] which can be produced by the production method 1 or the production method 5 in the absence of a solvent or in the presence of a salt group in a solvent. Alternatively, it can be produced by reacting in the absence. The compound [1-9] is usually produced at a reaction temperature of 0 to 150 ° C, preferably 0 to 100 ° C, for 10 minutes to 24 hours. The amount of the reagent used in the reaction is preferably compound [h], compound [r] or a base equivalent to 1 equivalent of the compound [1-7〗, but may be arbitrarily changed depending on the reaction situation. Can be done. Examples of the base include those similar to the production of compound [1-3] from compound [1-2] of production method 2. Examples of the solvent include those similar to those in Production method 4.

<Production method 8>

 The compound [1-11] of the present invention can be produced as follows.

(Wherein, R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₁₂ , R] ₆ , L and p each have the same meaning as described above.)

 Compound [1-11] of the present invention can be produced by reacting compound [10] with compound [e] in a solvent in the presence of a base.

The compound [1-11] is usually produced at a reaction temperature of 0 to: 120 ° C, preferably 0 to 80 ° C, for 10 minutes to 24 hours. The amount of reagent used in the reaction depends on the compound [1-10] One equivalent of compound [e] and base is desirable per equivalent, but can be arbitrarily changed according to the reaction situation. Examples of the base and the solvent include those similar to those in Production method 4.

Manufacturing method 9〉

 The compound [1-12] of the present invention can be produced as follows.

(Wherein, R ₂ , R ₃ , R ₄ , R ₅ , Re Y and p each have the same meaning as described above, and R ₂₁ is a cycloalkyl group, an aromatic heterocyclic group, an aryl group or a formyl group. Represents an acyl group other than.)

 The compound of the present invention [1-13] is a compound [1-12] which can be produced by reacting the compound [1-2] produced by the above-mentioned production method 2 with the compound [s] in a solvent. It can be produced by reacting compound [u] or compound [V] in a solvent in the presence of a catalytic amount of iron (II) chloride.

 In the production of compound [1-12], the reaction is usually carried out at a reaction temperature of 0 to: L20 ° (preferably at 0 to 80 ° C for 10 minutes to 24 hours.

[1-2] One equivalent of compound [s] is desirable per equivalent, but can be arbitrarily changed according to the reaction situation. As the solvent, for example, those similar to the production method 4 can be mentioned. The compound [1-13] is usually produced at a reaction temperature of -70 to 120, preferably -70 to 80 ° C, for 10 minutes to 24 hours. The amount of the reagent used in the reaction is 2 to 4 equivalents of compound [u] or compound [V] and 0.01 to 1 equivalent of iron chloride (II) per 1 equivalent of compound [1-12]. Examples of the solvent include ethers such as getyl ether and tetrahydrofuran, aromatic hydrocarbons such as benzene and toluene, aliphatic hydrocarbons such as hexane and heptane, and mixtures thereof.

 The methods of Production Methods 2 to 7 can also be used for producing the compounds [V '], [VI], [νπ'], [VIII], and [IX] described in Production Method 1.

 Next, the production method, formulation method and use of the compound of the present invention will be specifically described with reference to examples.

<Production Example 1>

 (1R, 2R, 6S) -5-Benzyl-1- (2-chlorobenzyloxy) 1-1,5-dimethyl-17-oxabicyclo [4.1.0] heptane (Compound Nos. 1-1 and 1-2 of the present invention) ) Manufacturing of

 (1) I.Og (5.6 mmol) of palladium chloride was suspended in 200 ml of N, N-dimethylformamide, and the temperature was raised to 140. After cooling to room temperature, 79 g (503 mmol) of bromobenzen, 54 g of /? _ Methanol alcohol

(749 mmol) and 50 g (593 mmol) of sodium hydrogencarbonate were added and heated under reflux for 3 hours. After cooling, 200 ml of toluene was added, the solid was filtered, and the organic layer was washed with water and saturated saline. After drying over anhydrous magnesium sulfate, the mixture was filtered and the solvent was distilled off. The residue was purified by distillation under reduced pressure (boiling point: ^ mmHg at 85) to obtain 45 g of 2-methyl-13-phenylpropanal (yield 60%). Obtained.

(2) 0.2 ml of concentrated sulfuric acid was added to a solution of 22.2 g (150 mmol) of 2-methyl-3-phenylpropanal and 12.6 g (150 mmol) of ethyl biliketone in 75 ml of benzene, followed by stirring at room temperature for 1 hour. . Thereafter, the mixture was refluxed for 3 hours using a Din Stark, and the generated water was distilled off. After cooling, ethyl acetate was added, and the organic layer was washed with water and saturated saline. After drying over anhydrous magnesium sulfate, filtration, and evaporation of the solvent, purification was performed by distillation under reduced pressure (boiling point: 125 ° C / 1.5 mmHg). 42.3 g (yield: 69%) of 4-benzyl-1,2,4-dimethyl-2-cyclohexene-11-one (Compound No. 2-2 of the present invention) was obtained as a pale yellow liquid.

 (3) In a nitrogen atmosphere, a solution of 1.0 g (3.6 mmol) of (S) _2-methyl-CBS-oxaboxyl lysine in 20 ml of tetrahydrofuran was cooled to 0 ° C, and a borane tetrahydrofuran complex (L08mol / 1) was added. 24 ml were added. Then, 4-benzyl-1-2,4-dimethyl-12-cyclohexene-one 7.72 g

A solution of (36 mmol) in 10 ml of tetrahydrofuran was added dropwise at 0 to 5, and after completion of the addition, the mixture was further stirred at 0 at 1 hour. Water and diluted hydrochloric acid were added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off to obtain (R) -4-benzyl-2,4-dimethyl-2-cyclohexene-1-ol. 7.78 g (100% yield) of the present compound No. 3-2) was obtained as a colorless liquid.

 () (R) -4-Benzyl-1,2,4-dimethyl-2-cyclohexene-1-ol 6.5 g (30 mmol) of a solution of 6.5 g (30 mmol) of formaldehyde in 250 ml of formaldehyde, 12.6 g (51 mmol) of m-chloroperbenzoic acid Was added and stirred at room temperature for 3 hours. The organic layer was washed with an aqueous solution of sodium hydrogen sulfite, an aqueous solution of saturated sodium hydrogen carbonate and water, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The crude product was purified by silica gel gel chromatography (developing solvent / n-hexane: ethyl acetate = 3: 1) to give (1R, 2R, 6S) -5-benzyl-1,5-diene 5.88 g (yield 84%) of methyl-2-hydroxy-1- 7-oxabicyclo [4.1.0] heptane (Compound No. 5-2 of the present invention) was obtained as a colorless liquid.

(5) (1R, 2R, 6S) -5-Benzyl-1,5-dimethyl-12-hydroxy-7-oxabicyclo [4.1.0] heptane 5.88 g (25.3 mmol), 2-cyclopentyl bromide 5.46 g ( To a solution of 26.6 mmol) in tetrahydrofuran (120 ml) was added 4.54 g (40 mmol) of potassium tert-butoxide, and the mixture was stirred at room temperature for 3 hours. The reaction solution was poured into water, extracted with ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The residue was separated and purified by silica gel column chromatography (developing solvent // n-hexane: ethyl acetate = 11: 1), and the desired (1R, 2R, 6S) — 5-benzyl 1,2- (2-chloro benzyloxy) 1,1,5-dimethyl-7-oxabicyclo mouth [4.1.0] heptane 3.53 g (Compound No. 1-1, diastereomer 1) and 3.31 g (Compound No. 1- 2. Diastereomer 2) was obtained (76% yield) ₀

<Production Example 2>

 (1R, 2R, 6S) -2- (2-chlorobenzyloxy) -1,5-dimethyl-5- (3-phenylmethyl) 17-oxabicyclo [4.1.0] heptane (Compound No. 1-129 of the present invention) 1-130) Manufacturing

 (1) 14.lg (243 mmol) of propanal was added dropwise to a solution of 25 g (223 mmol) of 3-thiophenecarboxaldehyde and 1.5 g (23 mmol) of potassium hydroxide in 150 ml of ethanol at 5X: below. After the dropwise addition, the mixture was stirred at 5 to 10 for 2 hours, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous sodium sulfate. After filtration and evaporation of the solvent, 31.2 g (yield 88.4%) of (2-methyl) -3-thiophenpropenal was obtained.

 (2) (2-Methyl) _3-thiophenepropenal 31g (201mmol), Ethylene glycol 60ml, Pyridinium para Toluenesulfonate 2.0g

A solution of (8 mmol) in benzene (300 ml) was refluxed for 8 hours using Dean-Stark to distill off the generated water. After cooling, the mixture was washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off. The crude product was distilled under reduced pressure (boiling point: 90 to 93 t: Z 8 mmHg) to obtain 33.9 g (yield 85.9%) of (2-methyl) -13-thiophenepropenal-ethylene ketal.

 (3) Dissolve 30 g (l52.9 mmol) of (2-methyl) -1-3-thiophenepropene-l-ethylene ketal in 600 ml of methanol and apply 3.0 g of 10% Pd / C at room temperature under normal pressure. Hydrogenated for hours. After removing the catalyst, methanol was distilled off to obtain 28 g of (2-methyl) -13-thiophenpropanal-ethylene ketal (yield 92.4%).

(4) To a solution of 300 ml of acetone, 80 ml of water and 2.0 g (8 mmol) of PPTS (pyridinium p-toluenesulfonic acid) was added 28 g (141.2 mmol) of (2-methyl) -13-thiophene propanal-ethylene ketal, and 12 Time return Shed. After the acetone was distilled off, water was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off. Distill the crude product (boiling point:

g) to obtain 19.8 g (yield 90.9%) of (2-methyl) -13-thiophenpropanal.

 (5) A solution of 15.4 g (100 mmol) of (2-methyl) -3-thiophenpropanal and 9 g (105.7 mmol) of piperidine in 200 ml of benzene was refluxed for 1 hour using Dean-Stark to remove water. Stayed. 12.0 g (142.6 mmol) of ethyl biliketone and 200 ml of ethanol were added to the crude enamine obtained by distilling off benzene, and the mixture was refluxed for 12 hours. After cooling, potassium acetate 18.7g

(190 mmol) and acetic acid (50 ml) were added, and the mixture was further refluxed for 12 hours. After cooling, the mixture was adjusted to pH 9 with a 10% aqueous sodium hydroxide solution and then refluxed for 8 hours. Ethanol was distilled off, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off. The crude product is purified by silica gel column chromatography (developing solvent: n-hexane: ethyl acetate = 4: 1) to give 2,4-dimethyl-41- (3-phenylmethyl) -12-cyclohexene-1 11.3 g (51.4% yield) of —one (Compound No. 2-25 of the present invention) was obtained as a pale yellow liquid.

 (6) 6.6 g (30 mmol) of 2,4-dimethyl-4- (3-Chenylmethyl) _2-cyclohexene-1-one in 100 ml of tetrahydrofuran (S) —2-methyl-CBS-oxaza Using 0.8 g (3 mmol) of borolidine and 21 ml of boranenote tetrahydrofuran complex (1.08 mol / 1), reduce according to Production Example 1- (3) and (R)-2,4_dimethyl-4- (3 —Chenylmethyl) -2-cyclohexene-1-ol (Invention compound No. 3-25) 6.1 g (yield 92.3%) was obtained as a colorless liquid.

(7) (R) — 2,4-Dimethyl-1 4_ (3-Chenylmethyl) 1-2-cyclohexene-1-ol 6. lg (27.4 mmol) in 100 ml of chloroform at _m- chloroperbenzoic acid Using 8.1 g (32.9 mmol) of acid (70%), oxidize according to Production Example 1- (4) to give (1R, 2R, 6S) -2-hydroxy-1,5-dimethyl-1- ( 3-Chenylmethyl) 1 7-oxabicyclo [4.1.0] heptane 4.9 g (75% yield) of a clear compound No. 5-25) was obtained as a colorless liquid.

 (8) (1R, 2R, 6S) -1,5-Dimethyl-1-hydroxy-5- (3-Chenylmethyl) -17-oxabicyclo [4.1.0] heptane 1.34 g (5.62 mmol), 2- 1.2 g (5.62 mmol) of benzylbutane chloride and 0.65 g (5.62 mmol) of potassium tert-butoxide were reacted in 50 ml of tetrahydrofuran according to Production Example 11- (5). The crude product was separated and purified by silica gel chromatography (developing solvent: Zn-hexane: ethyl acetate = 10: 1), and (1R, 2R, 6S) -2- (2-chlorobenzyloxy) 0.85 g (Compound No. 1-129 of the present invention, diastereomer 1) and 0.85 g (Compound No. 1-130 of the present invention), 1,5-dimethyl-1-5- (3-phenylmethyl) -17-oxabicyclo [4.1.0] heptane Diastereomer 2) was obtained (81.3% yield).

<Production Example 3>

 (1S, 5R, 6R) -N-[5- (2-Fluorobenzyloxy) -1,2,6-dimethyl-17-oxabicyclo [4.1.0] hept-2-yl] N-methylformamide Preparation of (Compound No. 1-341 of the present invention, diastereomer 2)

(1) Synthesized according to Production Example 1 (IS, 5R, 6R) -5- (2-Fluorobenzoyloxy) 1,2,6-dimethyl-7-oxabicyclo [4.1.0] heptane-2-2-capronic acid 20.2 g of ethyl ester (Diastereomer 2)

To a solution of (62.7 mmol) in 200 ml of ethanol was added 20 g (125 mmol) of a 25% aqueous sodium hydroxide solution, and the mixture was stirred at 70 for 4 hours. Water was added to the reaction solution, and the mixture was washed with a mixed solution of hexane and ether, and then ethanol in the aqueous layer was distilled off. The aqueous layer was acidified with 10% hydrochloric acid, extracted with ethyl acetate, and the organic layer was washed with water and saturated saline. After drying over anhydrous magnesium sulfate, the crude product obtained by filtration and evaporation of the solvent was recrystallized from hexanediisopropyl ether.

(1 S, 5R, 6R) -5- (2-Fluorobenzyloxy) 1,2,6-dimethyl-7-oxabicyclo [4.1.0] heptane-12-carboxylic acid (diasteromer 2) 14.5 g (79% yield) as white crystals.

mp = 84-85 ° C; Ή- NMR (CDC1 3 / TMS) S (ppm): 1.02-1.12 (m, lH), 1.36 (s, 3H), 1.43 (s, 3H), 1.61-1.76 (m , 2H), 2.21-2.27 (m, lH), 3.04 (s, lH). 3.69 (dd, lH), 4.66 (ABq, 2H), 7.03 (t, lH), 7.14 (t, lH), 7.27 (dd, 1H), 7.47 (t, lH).

 (2) (IS, 5R, 6R) -5- (2-Fluorobenzyloxy) -1,2,6-dimethyl-17-oxabicyclo [4.1.0] heptane-12-carboxylic acid (Diastereoma-1 2) ) 12.3 g (38.2 mmol), 10.5 g of diphenylphosphoric acid azide

(38.2 mmol) and a solution of 4.3 g (42.5 mmol) of triethylamine in 100 ml of t-butanol were stirred at 90 ° C. for 6 hours. The reaction solution was concentrated, ether was added, and the organic layer was washed with water and saturated saline. After drying over anhydrous magnesium sulfate, the mixture was filtered and the solvent was distilled off. The resulting crude product was purified by silica gel column chromatography (developing solvent: Zn-hexane: ethyl acetate = 5: 1) to give (1R, 2R, 6S) —2— (2-Fluorobenzyloxy) -1-5-isosocyanato-1,5-dimethyl-17-oxabicyclo [4.1.0] heptane (Compound No. 1-568 of the present invention, diastereomer 2) 8.66 g (78% yield) as a colorless liquid.

 (3) (1R, 2R, 6S) —2— (2-Fluorobenzyloxy) -1-5-isocyanato-1,5-dimethyl-7-oxabicyclo [4.1.0] heptane (diastereomer 2) 8.66 While stirring a solution of g (29.7 mmol) in 80 ml of methanol and 10 ml of water at 01 :, 1.2 g (31.7 mmol) of sodium borohydride was added little by little. After stirring at 0 ° C for 1 hour, the mixture was stirred at room temperature for 1 hour. Dilute hydrochloric acid was added to the reaction solution, and after extraction with ethyl acetate, the organic layer was washed with water and saturated saline. The crude product was recrystallized from hexane-diisopropyl ether after drying over anhydrous magnesium sulfate, followed by filtration and removal of the solvent.

(IS, 5R, 6R) 1- [5- (2-furrobenzyloxy) -1-6-methyl-7-oxabicyclo [4.1.0] hept-2-yl] -formamide (Compound No. 1-336 of the present invention) Diastereomer 2) 7.03 g (81% yield) was obtained as white crystals.

 (4) (IS, 5R, 6R)-[5- (2-Fluorobenzyloxy)-1,2,6-dimethyl_7-oxabicyclo [4.1.0] hept-2-yl] -formamide

(Diastereomer 2) 1.03 g (3.51 mmol) of N, N-dimethylform While stirring the amide 40 ml solution at room temperature, 0.3 g (7.5 mmol) of 60% sodium hydride was added, and then 1.5 g (l0.6 mmol) of methyl iodide was added. Thereafter, the mixture was stirred at 40 ° C for 2 hours, the reaction solution was poured into water, and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed. The resulting crude product was purified by silica gel gel chromatography (developing solvent ethyl acetate). (1S, 5R, 6R) -N- [5- (2-Fluorobenzyloxy) 1-2,6-dimethyl-7-oxabicyclo [4.1.0] hept-2-yl] — N-methylformami 0.75 g (yield 70%) of the compound (Compound No. 1-341 of the present invention, diastereomer 2) was obtained as a colorless liquid.

<Production Example 4>

 (1 S, 5R, 6R) — 2,2,2-trifluoro N— [5- (2-fluorobenzoyloxy) -1,2,6-dimethyl-7-oxabicyclo [4.1.0] hept-1-yl ] — Production of N-methylacetamide (Compound No. 1-348 of the present invention, diastereomer 2)

 (1) (IS, 5R, 6R) 1- [5- (2-Fluorobenzyloxy) -2,6-dimethyl-17-oxabicyclo [4.1.0] hept-2-yl] —formamide

20 g (50 mmol) of a 10% aqueous sodium hydroxide solution was added to a solution of 7.03 g (24 mmol) of (diastereomer 2) in 100 ml of ethanol, and the mixture was heated under reflux for 4 hours. Ethanol was distilled off from the reaction solution, and after extraction with chloroform, the organic layer was washed with water. After drying over anhydrous magnesium sulfate, filtration and evaporation of the solvent

(1S, 5R, 6R) .- 5- (2-Fluorobenzyloxy) -1,2,6-dimethyl-17 oxabicyclo [4.1.0] heptoh-2-ylamine (Compound No. 1-330 of the present invention) 6.30 g (99% yield) of diastereomer 2) were obtained as a colorless liquid.

(2) (IS, 5R, 6R) 15- (2-fluorobenzyloxy) 1,2,6-dimethyl-7-oxabicyclo [4.1.0] heptoto-2-ylamine (Diastereomer 2) 3.50g (13.2 mmol) and 2.67 g (26.4 mmol) of triethylamine in 100 ml of ethyl acetate were cooled to −10 ° C., and trifluoroacetic anhydride 3.6 (l7.1 mmol) was added dropwise. After stirring at 110 ° C for 30 minutes, the reaction solution was poured into aqueous citric acid solution. After extraction with ethyl acetate, the organic layer was washed with water and saturated saline. After drying over anhydrous magnesium sulfate, the mixture was filtered and the solvent was distilled off. The resulting crude product was purified by silica gel gel chromatography (developing solvent Zn-hexane: ethyl acetate = 4: 1), 1S, 5R, 6R) -2,2,2-Trifluoro-N— [5- (2-fluorobenzyloxy) -1-2,6-dimethyl-7-oxabicyclo [4.1.0] hept-2-yl 4.53 g (95% yield) of acetoamide (Compound No. 1-347 of the present invention, diastereomer 2) was obtained as a colorless liquid.

 (3) (1S, 5R, 6R) — 2,2,2_ trifluoro-N— [5- (2-fluorobenzyloxy) -1,2,6-dimethyl-7-oxabicyclo [4.1.0] hept-1-2_yl] While stirring a solution of 0.65 g (1.80 mmol) of acetoamide (diastereomer 2) in 20 ml of N, N-dimethylformamide at room temperature, 0.16 g (4.0 mmol) of 60% sodium hydride was added, and then 0.85 g of methyl iodide was added. g

(6.0 mmol) was added. Thereafter, the mixture was stirred at 40 ° C for 2 hours, the reaction solution was poured into water, and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The resulting crude product was subjected to silica gel column chromatography (developing solvent Zn-hexane: ethyl acetate). (4: 1) to give (1S, 5R, 6R.) — 2,2,2-Trifluoro-1-N— [51- (2-Fluorobenzyloxy) -1,2,6-dimethyl-1- 7-oxabisik mouth [4.1.0] hept-2-yl] -N-methylacetoamide (Compound No. 1-348 of the present invention, diastereomer 2) 0.38 g (yield 56%) was converted to white needles. I got it. -<Production Example 5>

 (1S, 5R, 6R) — 1- [5- (2-Fluorobenzyloxy) 1,2,6-dimethyl-7-oxabicyclo [4.1.0] hept-1-yl] _3-phenylthioperea ( Production of Compound Nos. 1-519, Diastereomers 2) of the Present Invention

(IS, 5R, 6R) 1-5— (2-Fluorobenzyloxy) 1,2,6-dimethyl-1 7-oxabicyclo [4.1.0] hept-12-ylamine (diastereo) A solution of 0.50 g (1.88 mmol) of mer 2) and 0.39 g (2.88 mmol) of phenyl isothiocyanate in 20 ml of tetrahydrofuran was heated to reflux for 1 hour. The crude product obtained by concentrating the reaction solution was purified by silica gel column chromatography (developing solvent: Zn-hexane: ethyl acetate 2: 1) to give (1 S, 5R, 6R) — 1- [5- (2-Fluorobenzyloxy) -1,2,6-dimethyl-17-oxabicyclo [4.1.0] hept-2-yl] -13-phenylthiodrea (Compound No. 1-519 of the present invention) Diastereomer 2) 0.64 g (yield 85%) was obtained as white crystals.

Manufacturing example 6>

 (1 S, 5R, 6R) —1— [5— (2-Fluorobenzyloxy) -1,2,6-dimethyl-17-oxabicyclo [4.1.0] hept-12-yl] ethanone (book Production of Compound No. 1-472, diastereomer 2)

 (1) (1S, 5R, 6R) -5- (2-Fluorobenzyloxy) 1,2,6-dimethyl-17-oxabicyclo mouth [4.1.0] heptane 1-2-carboxylic acid (Diastereomer 2) ) To a solution of 3.50 g (ll.9 mmol) in 35 ml of tetrahydrofuran was added 2.12 g (I3.0 mmol) of 1,1'-forced carbonylyl-1H-imidazole and stirred at 60 ° C for 1 hour. The reaction solution was poured into water, extracted with ethyl acetate, and the organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. Mouth chromatography

(Developing solvent / n-hexane: ethyl acetate = 1: 3) to give (1S, 5R, 6) -1- [5- (2-fluorobenzyloxy) -1,2,6-dimethyl- 7-oxabicyclo [4.1.0] hepto-2-yl] imidazoyl-1-ylmethanone (Invention No. 1-310, diastereomer 2) 3:36 g ^: (82% yield) was obtained as a colorless liquid.

 (2) Under a nitrogen atmosphere, (1S, 5R, 6R) -1-1- [2- (2-fluorobenzyldioxy) -1,2,6-dimethyl-7-oxabicyclo [4.1.0] hepto-2-yl] imidazole-1 —Ilmetanone (diasteromer 2) 1.96g

(5.70 mmol) in 40 ml of tetrahydrofuran was cooled to −10, 0.10 g (0.62 mmol) of anhydrous iron (III) chloride was added, and then 0.93 M methylmagnesium bromide was added. 24 ml (22.3 mmol) of Nesium Z tetrahydrofuran solution was dropped over 10 minutes. Immediately after the dropwise addition, the reaction solution was poured into water and extracted with ethyl acetate.The organic layer was washed with dilute hydrochloric acid, water and saturated saline, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The crude product was purified by silica gel column chromatography (developing solvent: Zn-hexane: ethyl acetate = 2: 1) to give (1S, 5R, 6R) —1— [5- (2-fluorobenzylo) Xy) 1,2,6-dimethyl-7-oxabicyclo [4.1.0] hept-2-yl] ethanone (Compound No. 1-472 of the present invention, diastereomer 1) 0.61 g (yield 37%) was obtained as a colorless liquid. Was.

Next, some IH-NMR of the examples of the present compound (S value (ppm), Solvent: CDC1 ₃ / TMS) shows the data.

Oh, 9Z8 OdT ψ

Re

Article 6

Compound

 1H-MR (5 values (ppm) solvent (CDCl / TMS)

 Number

 1-25 0.64-1.79 (m, 4H), 0.86 & 0.91 (s, 3H), 1.26 & 1.41 (d, 3H), 1.34 & 1.43 (s, 3H),

 226 & 282is lff »306-316Cm 1H) 365-370Cm 1H) 461-4 l ^ im 2Ή

 7.04 (t, lH), 7.12-7.37 (m, 7H), 7.52 (d, lH)

1-26 0.99 & 1.12 (s, 3H), 1.17 & 1.42 (s, 3H), 1.30 & 1.32 (d, 3H), 1.10-1.65 (m, 4H), 2.65-,, ±) j No , T, no,

7.30 (m, 8H), 7.40-7.50 (m, lH)

1-27 0.95 (s, 3H), 1.02-1.12 (m, lH), 1.45 (s, 3H), 1.61-1.80 (m, 3H), 2.61 (s, lH), 7.60 (d, lH)

1-28 1.13 (s, 3H), 1.25-1.40 (m, 2H), 1.41 (s, 3H), 1.57-1.76 (m, 2H), 2.85 (ABq, 2H), .85 cn

 (S, ll l), d.bU (dCl, 丄 ± 1 \), 4ό / (± Μ¾, 2ϋ ^, .lo- /.ob(m, ixl,), .u (α, 1x1

1-29 0.94 (s, 3H), 1.01-l.ll (m, lH), 1.41 (s, 3H), 1.59-1.82 (m, 3H), 2.60 (s, lH),

i), 4. l (, Ai q, xl f .Ul- .o4 (m, orl)

1-30 1.12 (s, 3H), 1.24-1.39 (m, 2H), 1.40 (s, 3H), 1.55-1.74 (m, 2H), 2.84 (ABq, 2H),

1-31 0.90 (s, 3H), 1.00-1.10 (m, lH), 1.42 (s, 3H), 1.50-1.55 (m, lH), 1.67-1.73 (m, 2H),

 7.59 (d, lH)

1-32 1.08 (s, 3H), 1.20-1.25 (m, 2H), 1.41 (s, 3H), 1.56-1.72 (m, 2H), 2.61 (ABq, 2H),

 W,, ^ ν (·

 7.54 (d, lH)

1-33 0.91 (s, 3H), 1.00-1.10 (m, lH), 1.39 (s, 3H), 1.50-1.56 (m, lH), 1.66-1.71 (m, 2H), 2.50 (s, lH) , 2.68 (ABq, 2H), 3.68 (dd, lH), 4.70 (ABq, 2H), 7.03 (t, lH), 7.12- 7.30 (m, 6H), 7.51 (t, lH)

1-34 1.06 (s, 3H), 1.18-1.22 (m, 2H), 1.37 (s, 3H), 1.54-1.69 (m, 2H), 2.59 (ABq, 2H), 2.79 (s, lH), 3.49 (dd, lH), 4.62 (ABq, 2H), 6.98-7.24 (m, 7H), 7.45 (t, lH) 91 / O10AV

9 / sso_

e

9sivofcl: £ S9 OAV

i 9 OAV

Compound

1H-NMR (5 value (ppm) solvent (CDC1 ₃ / TMS)

 w

 1-622 0.86-1.80 (m, 15H), 1.02 (s, 3H), 1.39 (s, 3H), 2.65 (s, lH), 3.58 (dd, lH),

 4.66 (ABq, 2H), 7.03 (t, lH), 7.13 (t, lH), 7.23-7.30 (m, lH), 7.48 (t, lH)

1-623 0.00-0.16 (m, 2H), 0.41-0.54 (m, 2H), 0.59-0.77 (m, lH), 1.00-1.76 (m, 6H),

 1.08 (s, 3H), 1.39 (s, 3H), 2.73 & 2.76 (s, lH), 3.63-3.69 (m, lH), 4.59-4.77 (m, 2H), 7.03 (t, lH), 7.14 ( t, lH), 7.23-7.28 (m, lH), 7.49 (t, lH)

1-633 0.01-015 (m, 2H), 0.41-0.47 (m, 2H), 0.71-0.77 (m, lH), 1.00-1.70 (m, 6H),

 1.10 (s, 3H), 1.45 (s, 3H), 2.75 (s, lH), 3.72 (dd, lH), 3.89 (s, 3H), 5.00 (ABq, 2H), 7.32 (t, lH), 7.53 (t, lH), 7.81 (d, lH), 7.93 (d, lH)

1-634 0.01-0.08 (m, 2H), 0.43-0.55 (m, 2H), 0.63-0.71 (m, lH), 1.10 (s, 3H), 1.20-1.78 (m, 6H), 1.44 (s, 3H), 2.78 (s, lH), 3.71 (dd, lH), 3.89 (s, 3H), 5.01 (ABq, 2H), 7.33 (t, lH), 7.54 (t, lH), 7.81 (d, lH ), 7.94 (d, lH)

1-657 1.37 (s, 3H), 1.54-1.84 (m, 4H), 2.64 (s, lH), 2.93 (ABq, 2H), 3.33 (s, 3H),

 3.73 (dd, lH), 4.70 (ABq, 2H), 7.04 (t, lH), 7.14 (t, lH), 7.19-7.37 (m, 6H), 7.49 (t, lH)

1-658 1.14-1.24 (m, lH), 1.39 (s, 3H), 1.47-1.81 (m, 3H), 2.87 (ABq, 2H), 2.97 (s, lH),

 3.50 (dd, lH), 3.54 (s, 3H), 4.63 (ABq, 2H), 7.02 (t, lH), 7.12 (t, lH), 7.18-7.37 (m, 6H), 7.45 (t, lH)

1-659 1.40 (s, 3H), 1.55-1.88 (m, 4H), 2.65 (s, lH), 2.94 (ABq, 2H), 3.34 (s, 3H),

 3.77 (dd, lH), 4.72 (ABq, 2H), 7.20-7.37 (m, 8H), 7.57 (d, lH)

1-660 1.16-1.26 (m, lH), 1.43 (s, 3H), 1.47-1.83 (m, 3H), 2.88 (ABq, 2H), 2.99 (s, lH),

 3.53 (dd, lH), 3.55 (s, 3H), 4.65 (ABq, 2H), 7.19-7.35 (m, 8H), 7.54 (d, lH)

1-662 0.80 (s, 3H), 0.80-0.89 (m, lH), 1.20-1.52 (m, 4H), 1.41 (d, 3H), 1.42 (s, 3H),

 2.45 (s, lH), 2.61 (ABq, 2H), 3.52 (dd, lH), 5.01 (q, 2H), 7.07-7.34 (m, 8H), 7.60 (d, lH)

1-663 0.86 & 1.03 (s, 3H), 0.90-1.70 (m, 4H), 1.28 & 1.45 (s, 3H), 1.42 & 1.47 (d, 3H), 2.42-3.02 (m, 3H) , 3.38-3.43 (m, lH), 4.97 & 5.16 (q, 2H), 7.10-7.35 (m, 8H), 7.59-7.67 (m, lH)

The herbicide of the present invention comprises a 2-benzyloxy-7-oxabicyclo [4.1.0] heptane derivative represented by the general formula [I] as an active ingredient.

 In order to use the compound of the present invention as a herbicide, the compound of the present invention may be used as it is, but a carrier, a surfactant, a dispersant, an auxiliary agent, or the like generally used for formulation is compounded. They can also be formulated into powders, wettable powders, emulsions, fine granules or granules and used.

 Carriers used in the formulation include, for example, solid carriers such as talc, bentonite, cres, kaolin, diatomaceous earth, white carbon, nickel silicate, calcium carbonate, slaked lime, silica sand, ammonium sulfate, urea, and isopropyne. And liquid carriers such as alcohol, xylene, cyclohexane, and methylnaphthalene.

 Examples of the surfactant and dispersant include metal salts of alkyl benzene sulfonic acid, metal salts of dinaphthyl methane disulfonic acid, alcoholic ester salts, alkyl aryl sulfonic acid salts, lignin sulfonic acid salts, polyoxyethylene glycol ether, and polyoxyethylene. Examples thereof include alkyl aryl ethers and polyalkylene sorbitan monoalkylates. Examples of the adjuvant include carboxymethyl cellulose, polyethylene glycol, arabia gum and the like. When using, dilute to an appropriate concentration and spray or apply directly.

 The herbicide of the present invention can be used by foliage application, soil application, or water application. The compounding ratio of the active ingredient is appropriately selected as required, but in the case of powder or granules, it is preferably from 0.01 to 1096 (weight), preferably from 0.05 to 5% (weight). It is better to select from the range as appropriate. In the case of a milk and a water-dispersible powder, it may be suitably selected from the range of 1 to 50% (weight), preferably 5 to 30% (weight).

The application rate of the herbicide of the present invention varies depending on the type of the compound used, the target weed, occurrence tendency, environmental conditions, and the dosage form to be used, but when used as it is as a powder or granule, it may be used as an active ingredient. It is appropriate to appropriately select from the range of 0.1 lg to 5 kg, preferably lg to 1 kg per 10 ares. When used in the form of a liquid, such as an emulsion and a wettable powder, it is appropriate to select from the range of 0.1 to 50, 000 ppm, preferably 10 to 10; Good.

 Further, the compound of the present invention may be mixed with an insecticide, a fungicide, another herbicide, a plant growth regulator, a fertilizer, and the like, if necessary.

 Next, the preparation method will be specifically described with reference to typical preparation examples. The types and compounding ratios of the compounds and additives are not limited to these, and can be changed in a wide range. In the following description, “parts” means parts by weight.

<Formulation Example 1> Wettable powder

 0.5 part of polyoxyethylene octylphenyl ether, 0.5 part of sodium salt of a condensate of formalin mononaphthalenesulfonate, 0.5 part of sodium salt of diatomaceous earth were added to 10 parts of the compound (1-1). 0 parts and 69 parts of clay are mixed and ground to obtain a hydrating agent.

<Formulation Example 2> Wettable powder

 0.5 parts of polyoxyethylene octylphenyl ether, 0.5 parts of sodium salt of a condensate of naphthalenesulfonic acid formalin and 0.5 parts of diatomaceous earth were added to 10 parts of the compound (1-1). Parts, 5 parts of white carbon and 64 parts of clay are mixed and ground to obtain a wettable powder.

<Formulation Example 3> Wettable powder

 To 10 parts of the compound (111) were added 0.5 parts of polyoxyethylene octylphenyl ether, 0.5 parts of sodium salt of a condensate of naphthalenesulfonic acid formalin, and 20 parts of diatomaceous earth. Parts, 5 parts of white bonbons and 64 parts of carbonated calcium are mixed and ground to obtain a wettable powder. Formulation Example 4> Emulsion

An equivalent mixture of xylene and isophorone was added to 30 parts of the compound (111). Then, 10 parts of a mixture of a surfactant, a polyoxyethylene sorbitan alkylate, a polyoxyethylene alkyl aryl polymer and an alkyl aryl sulfonate are added, and the mixture is stirred well to obtain an emulsion.

<Formulation Example 5> Granules

 10 parts of the compound (1-1), 80 parts of a bulking agent obtained by mixing talc and bentonite at a ratio of 1: 3, 5 parts of white carbon, surfactant polyoxyethylene sorbitan alkylate, poly 10 parts of water was added to 5 parts of the mixture of the oxyethylene alkyl aryl polymer and the alkyl aryl sulfonate, and the mixture was kneaded well and extruded through a sieve having a diameter of 0.7 mm and dried. Later cut into 0.5-1 mm length to get granules.

 Next, the effects of the compound of the present invention will be described with reference to Test Examples.

<Test Example 1> Herbicidal effect test by paddy soil treatment

100 cm ² plastic pots were filled with paddy soil, and after generation, seeds of Tainubie (Ec 0) and Konagi (Mo) were sown and submerged to a depth of 3 cm. The next day, the wettable powder prepared according to Formulation Example 1 was diluted with water and dropped on the water surface. The application rate was 100 g of active ingredient per 100 ares. After that, the plants were grown in a greenhouse, and on the 21st day after the treatment, the herbicidal effect was examined according to the criteria in Table 93. The results are shown in Tables 94 to 97.

Index Herbicidal effect (degree of growth suppression) and phytotoxicity

Herbicidal effect of more than 590% suppression, phytotoxicity

470% to less than 90% weeding effect, street treasure

350% to less than 70% weeding effect, barbaric

230% or more and less than 50% herbicidal effect,

Herbicidal effect of 110% or more and less than 30%, basic ri insect

0% to less than 10% weeding effect, treasure

Dosage Herbicidal effect Compound number gai / 10a Ec Mo

1-65 100 5 5

1-66 100 5 5

1-67 100 5 5

1-68 100 5 5

1-69 100 5 5

1-70 100 5 5

1-71 100 5 4

1-72 100 5 5

1-73 100 5 5

1-74 100 5 5

1-76 100 5 5

1-77 100 5 4

1-78 100 5 5

1-79 100 5 4

1-80 100 5 5

1-81 100 5 5

1-82 100 5 5

1-83 100 5 5

1-84 100 5 5

1-87 100 5 5

1-88 100 5 4

1-89 100 5 5

1-90 100 5 5

1-93 100 5 5

1-94 100 5 5

1-95 100 5 5

1-96 100 5 5

1-105 100 5 5

1-106 100 5 5

1-107 100 5 5

1-108 100 5 5

1-109 100 5 5

1-110 100 5 5

1-117 100 5 5

1-118 100 5 5

1-119 100 5 5

1-120 100 5 5

1-129 100 5 5

1-130 100 5 5

1-131 100 5 5

1-132 100 5 5

1-153 100 5 5

1-154 100 5 5

1-155 100 5 5

1-156 100 5 5

1-159 100 5 5

1-160 100 5 5

1-191 100 5 5

1-192 100 5 5

1-193 100 5 5

¾ 9 7

 畺 "Herbicidal effect Compound number gai / lOa Mo

1-617 100 5 5

1-618 100

 1-619 100 5 A

1-621 100 K

 % j

1-622 100 5 5

1-623 100 5 5

1-657 100 5 5

1-658 100 5 5

1-659 100 5 5

1-660 100 5 5

1-664 100 5 5

1-665 100 5 5

<Test Example 2> Herbicidal effect test by upland soil treatment

80 cm ² plastic pots were filled with field soil, seeds of Echinochloa (E c) and Enochorogusa (Se) were sown and covered. The wettable powder prepared according to Formulation Example 1 is diluted with water, and 100 1 per 100 ares is evenly distributed on the soil surface using a small sprayer so that the active ingredient is 100 g per 100 ares. Sprayed. After that, the plants were grown in a greenhouse and the herbicidal effect was investigated on the 21st day of treatment according to the criteria in Table 93. The results are shown in Table 98 and Table 99.

¾ 9?

 Dosage Herbicidal activity Compound number gai / lOa Ec Se -370 100 5 5 -390 100 5 4 -392 100 5 4 -395 100 5 5 -416 100 5 5 -445 100 5 4 -446 100 5 5

1-447 100 5 5

1-448 100 5 5

1-454 100 5 5

1-472 100 5 5

1-484 100 K

1-497 100

 -543 100

 1-568 100 Pi K

1-613 100 A

1-614 100 κ

 1-615 100 ο Ό

1 -616 100 κ Ό

1-617 100 K

1-618 100 5 5

1-621 100 5 5

1-622 100 5 5

1-623 100 5 5

1-657 100 5 5

1-658 100 5 5

1-659 100 5 5

1-660 100 5 5

1-665 100 5 4

<Test Example 3> Test of herbicidal effect by upland foliar treatment

80 cm ² plastic pots were filled with field soil, seeds of Echinochloa (E c) and Enocorogosa (S e) were sown, and cultivated in a greenhouse for two weeks, and wettable powder prepared according to Formulation Example 1. Was diluted with water, and 100 1 per 100 ares was sprayed with foliage from the upper side of the plant using a small sprayer so that the active ingredient was 100 g per 100 ares. After that, the plants were grown in a greenhouse, and on the 14th day of the treatment, the herbicidal effect was examined according to the criteria in Table 93. The results are shown in Table 100.

<Test Example 4> Crop selectivity test by upland soil treatment

600 cm ² plastic pots were filled with field soil, and seeds of barnyardgrass (Ec;), genocologusa (Se) and soybean (G1) were sown and covered with soil. The wettable powder prepared according to Formulation Example 1 was diluted with water, and 1001 per 100 ares was uniformly sprayed on the soil surface using a small sprayer so that the effective component per 100 ares was 100 g. Sprayed. After that, the plants were grown in a greenhouse and the herbicidal effect was investigated on the 21st day of treatment according to the criteria in Table 93. For comparison, the compounds described in WO97 / 022858 shown in Table 101 were used. The compounds described in WO 9/02258 are inferior in stability and have a problem in practicality, but the compounds of the present invention are excellent in stability and high in practicality. The results are shown in Table 102. Table 101,

Compounds described in WO97 / 02258

Table 102 ¾ Herbicidal effect ire treasure Compound number (gai / lOa) Ec Se Gl

1-3 25 5 5 0

 6.3 5 4 0

1-108 25 5 5 0

 6.3 4 4 0

1-194 25 5 5 2

 6.3 4 4 1

1-347 25 5 5 4

 6.3 5 5 1

1-348 25 5 5 1

 6.3 5 5 0

1-353 25 5 5 0

 6.3 5 5 0

1-447 25 5 5 0

 6.3 5 5 0

1-448 25 5 5 0

 6.3 5 4 0

1-617 25 5 5 3

 6.3 5 5 1

1-618 25 5 5 1

 6.3 5 5 1

1-621 25 5 5 0

 6.3 5 4 0

1-622 25 5 5 0

 6.3 cr

 O O 0

1-657 25 5 5 o

 6.3 5 5 0

1-658 25 5 5 0

 6.3 5 4 0

1-659 25 5 4 0

 6.3 4 4 0 Compare 1 25 5 4 5

6.3 5 2 4 Industrial applicability

 The compound of the present invention represented by the general formula [I] can be used for various weeds that are problematic in the field, such as broadleaf weeds such as oynutade, aobu, shiroza, hakobe, ichibi, american sika deer, american cuckooxanem, asagao, and fonamimi. And perennial and first-year varieties such as hamazuge, yellowtail maggot, balsam pears, california and kogomegayari. It exhibits excellent herbicidal effects over a wide range of growing seasons. It is also possible to control annual weeds, such as barnyardgrass, tamagayari and konagi, which occur in paddy fields and perennial weeds such as perica, omodada, mizugayari, krogwai, firefly and heramodaka.

 On the other hand, the herbicide of the present invention has high safety against crops, and particularly shows high safety against rice, wheat, wheat, corn, grain sorghum, soybean, potato, sugar beet, and the like.

Claims

Claims General formula [I]

In the formula, and R ₂ are the same or different, and represent a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group, an alkoxycarbonyl group, an asinole group, a cyano group, or Represents a dinitro group,

R ₃ represents a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group or an alkoxy group, and p represents an integer of 0 to 3 (when p is an integer of 2 to 3, R ₃ represents one or different May be)

R ₄ represents a hydrogen atom, an alkyl group or an alkoxy group,

R ₅ represents a hydrogen atom, an alkyl group or a benzyl group,

R ₆ represents a hydrogen atom, an alkyl group, a benzyl group or an alkoxy group,

R ₇ is an acyl group, a cycloalkyl group, an isocyanate group, an aromatic heterocyclic group (the group may be substituted with 1 to 4 identical or different substituents selected from the following substituent groups) Examples of the substituent group include a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyteralkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, an alkoxyalkoxy group, an alkoxycarbonylalkoxy group, and a cyanoalkoxy group. Group, a carbamoylalkoxy group (the nitrogen atom of the group is the same or different and a hydrogen atom or an alkyl group is substituted), an alkylthio group, an alkylsulfonyl group, an acryl group, an alkoxycarbonyl group, a cyano group, a carbamoyl group (The nitrogen atom of the group is the same or different, and A nitrogen atom is the same or different, and a hydrogen atom, an alkyl group, an acyl group, a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, an alkylsulfonyl group, A haloalkylsulfonyl group or a cycloalkylalkylsulfonyl group is substituted), and two adjacent lower alkoxy groups may be bonded to each other to form a lower alkylenedioxy group. ),

General formula,

— C ⁸ — ϊ¾ [II]

 0

[Wherein, R ₈ represents a hydrogen atom, an alkyl group or an alkoxy group,

R ₉ represents a hydrogen atom or an alkyl group, and R ₉ may form a carbonyl group together with these bonded carbon atoms;

R ₁₀ is a cycloalkyl group, an aromatic heterocyclic group, or an aryl group (where the aromatic heterocyclic group and aryl group are 1 to 4 identical or different groups selected from the following substituent groups) It may be substituted by different substituents.

Examples of the substituent group include a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, a haloalkoxy group, an alkoxyalkoxy group, an alkoxycarbonylalkoxy group, and a cyanoalkoxy. Group, force rubamoylalkoxy group (the nitrogen atom of the group is the same or different, and hydrogen atom or alkyl group is substituted), alkylthio group, alkylsulfonyl group, acyl group, alkoxycarbonyl group, cyano group, force Rubamoyl group (the nitrogen atom of the group is the same or different and hydrogen atom or alkyl group is substituted), nitro group or

Amino group (the nitrogen atom of the group is the same or different, and is a hydrogen atom, an alkyl group, an acyl group, a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, an alkylsulfonyl group, a haloalkylsulfonyl group or a cycloalkyl group. An alkylalkylsulfonyl group is substituted), and two adjacent lower alkoxy groups may be bonded to each other to form a lower alkylenedioxy group. )] Or a general formula,

[Wherein, represents a hydrogen atom, an alkyl group, a cycloalkylalkyl group, an alkenyl group, an alkynyl group, an alkoxyalkyl group, an alkylthioalkyl group or an alkoxycarbonylalkyl group,

 Rl2 is a hydrogen atom, an alkyl group, an acyl group, a peroxyalkylcarbonyl group, a cycloalkylalkylcarbonyl group, a cycloalkylcarbonyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an alkylsulfonyl group , A nonalkylalkylsulfonyl group, a cycloalkylalkylsulfonyl group, a cycloalkylsulfonyl group, an optionally substituted benzylsulfonyl group, an optionally substituted phenylsulfonyl group, an alkoxycarbonyl group, an optionally substituted benzyloxycarbonyl Group, phenyloxycarbonyl group, carbamoyl group which may be substituted (the same or different nitrogen atom as hydrogen atom, alkyl group, benzyl group which may be substituted or phenyl group which may be substituted) Is replaced) or Represents a moyl group (the group is the same as or different from a nitrogen atom, and is substituted by a hydrogen atom, an alkyl group, an optionally substituted benzyl group or an optionally substituted phenyl group). ] 2_benzyloxy-17-oxabicyclo [4.1.0] heptane derivative represented by ί.

2. General formula [IV]

 In formula I,

 And R2 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group,

R ₃ represents a halogen atom, an alkyl group or an alkoxy group, p represents an integer of 0 to 2 (when p is 2, R ₃ may be the same or different),

R ₅ represents an alkyl group,

R ₆ represents an alkyl group; R ₇ represents an acyl group, a cycloalkyl group, an isocyanate group, an aromatic heterocyclic group (the group may be one to four identical or four identical groups selected from the following substituent groups) May be substituted with different substituents.The substituent groups include a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, and an alkoxyalkoxy. Group, alkoxycarbonylalkoxy group, cyanoalkoxy group, carbamoylalkoxy group

(The nitrogen atom of the group is the same or different and a hydrogen atom or an alkyl group is substituted.), An alkylthio group, an alkylsulfonyl group, an acyl group, an alkoxycarbonyl group, a cyano group, a carbamoyl group (the nitrogen atom of the group is The same or different, a hydrogen atom or an alkyl group is substituted), a nitro group or an amino group (the nitrogen atom of the group is the same or different and a hydrogen atom, an alkyl group, an acyl group, a noloalkylcarbonyl group, a cycloalkyl group) An alkylalkylcarbonyl group, an alkylsulfonyl group, a haloalkylsulfonyl group or a cycloalkylalkylsulfonyl group is substituted), and two adjacent lower alkoxy groups are bonded to each other to form a lower alkylenedioxy group. You can. ),

General formula,

[Wherein, R ₈ represents a hydrogen atom, an alkyl group or an alkoxy group, R ₉ represents a hydrogen atom or an alkyl group, and R ₈ and R ₉ represent a carbonyl group together with the carbon atoms to which they are bonded. It may be formed. R ₁₀ is a cycloalkyl group, an aromatic heterocyclic group, an aryl group (where the aromatic heterocyclic group and the aryl group are one to four identical or different substituents selected from the following substituent groups) Examples of the substituent group include a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, a haloalkoxy group, an alkoxyalkoxy group, Alkoxycarbonylalkoxy group, cyanoalkoxy group, alkamoylalkoxy group (the nitrogen atom of the group is the same or different and hydrogen atom or alkyl group is substituted), alkylthio group, alkylsulfonyl group, acryl group, alkoxycarbonyl Group, a cyano group, a carbamoyl group (the nitrogen atom of the group is One or different hydrogen atoms or alkyl groups are substituted), nitro groups or amino groups (the nitrogen atoms of the groups are the same or different and are a hydrogen atom, an alkyl group, an acyl group, a haloalkyl group, a rubonyl group, a cycloalkylalkyl A carbonyl group, an alkylsulfonyl group, a noloalkylsulfonyl group or a cycloalkylalkylsulfonyl group is substituted), and two adjacent lower alkoxy groups are bonded to each other to form a lower alkylenedioxy group. Or a general formula;

[III]

Wherein, R _u represents a hydrogen atom, an alkyl group, a cycloalkyl group, § alkenyl group, an alkynyl group, an alkoxyalkyl group, an alkyl thio Al R ₁₂ represents a hydrogen atom, an alkyl group, an acyl group, a haloalkylcarbonyl group, a cycloalkylalkylcarbonyl group, a cycloalkylcarbonyl group, a benzylcarbonyl group which may be substituted, Benzoyl group, alkylsulfonyl group, haloalkylsulfonyl group, cycloalkylalkylsulfonyl group, cycloalkylsulfonyl group, optionally substituted benzylsulfonyl group, optionally substituted phenylsulfonyl group, alkoxycarbonyl group An optionally substituted benzyloxycarbonyl group, an optionally substituted phenoxycarbonyl group, or a substituted rubamoyl group (the same or different nitrogen atom as a hydrogen atom, an alkyl group, Good benzyl or substituted A phenyl group which may be substituted) or a thiocarbamoyl group

(The group is the same or different and a nitrogen atom is substituted by a hydrogen atom, an alkyl group, an optionally substituted benzyl group or an optionally substituted phenyl group). ] 2 2-benzyloxy-1 7-oxabicyclo

[4.1.0] Heptane derivatives.

3. In any one of claims 1 and 2, wherein R ₇ is an acyl group, a cycloalkyl group, an aromatic heterocyclic group (the group is selected from the following substituent groups: And may be substituted by four identical or different substituents .. The substituent group includes a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, and an alkylsulfonyl group. Alkyl group, alkoxy group, alkoxyalkoxy group, alkoxycarbonylalkoxy group, cyanoalkoxy group, rubamoylalkoxy group (the nitrogen atom of the group is the same or different, and a hydrogen atom or an alkyl group is substituted), an alkylthio group , Alkylsulfonyl, acyl, alkoxycarbonyl, cyano, carbamoyl ( Hydrogen atoms or alkyl groups are the same or different, and a hydrogen atom or an alkyl group is substituted), a nitrogen atom or an amino group (the nitrogen atoms of the groups are the same or different and are a hydrogen atom, an alkyl group, an acyl group, a haloalkylcarbonyl Group, alkyl alkylcarbonyl group, alkylsulfonyl group, haloalkyl A lower alkylenedioxy group is substituted), and two adjacent lower alkoxy groups may be bonded to each other to form a lower alkylenedioxy group. ) Or a general formula,

RRCII

 81

[Wherein, R ₈ represents a hydrogen atom, an alkyl group or an alkoxy group, R ₉ represents a hydrogen atom or an alkyl group, and R ₈ and R ₉ represent a carbonyl group together with the carbon atoms to which they are bonded. It may be formed. R ₁₀ is a cycloalkyl group, an aromatic heterocyclic group, an aryl group (where the aromatic heterocyclic group and the aryl group are 1 to 4 identical or different substituents selected from the following substituent groups) The substituent group includes a hydrogen atom, a halogen atom, an alkyl group, a fluoroalkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an alkylsulfonylalkyl group, an alkoxy group, a haloalkoxy group, and an alkoxy group. Alkoxy group, alkoxycarbonylalkoxy group, cyanoalkoxy group, carbamoylalkoxy group (the nitrogen atom of the group is the same or different and hydrogen atom or alkyl group is substituted), alkylthio group, alkylsulfonyl group, and acyl group , An alkoxycarbonyl group, a cyano group, a carbamoyl group (the nitrogen atom of the group Are the same or different and a hydrogen atom or an alkyl group is substituted), a nitro group or an amino group (the nitrogen atoms of the groups are the same or different and are a hydrogen atom, an alkyl group, an acyl group, a haloalkyl group, a rubonyl group, a cycloalkylalkyl (A carbonyl group, an alkylsulfonyl group, a noloalkylsulfonyl group or a cycloalkylalkylsulfonyl group is substituted), and two adjacent lower alkoxy groups are bonded to each other to form a lower alkylenedioxy group. 2) -benzyloxy-7-oxabicyclo [4.1.0] heptane derivative.

4. Any one of claims 1 and 2 R ₇ is an isocyanate group or a general formula;

[III]

Wherein, Rn is hydrogen atom, an alkyl group, a cycloalkyl group, § alkenyl group, an alkynyl group, an alkoxyalkyl group, an alkyl thio al Kill group or alkoxycarbonylalkyl group, R ₁₂ is a hydrogen atom, an alkyl group, Ashiru Group, noloalkylcarbonyl group, cycloalkylalkylcarbonyl group, cycloalkylcarbonyl group, optionally substituted benzylcarbonyl group, optionally substituted benzoyl group, alkylsulfonyl group, Alkylalkylsulfonyl group, cycloalkylsulfonyl group, optionally substituted benzylsulfonyl group, optionally substituted phenylsulfonyl group, alkoxycarbonyl group, optionally substituted benzyloxycarbonyl group, substituted May be Enoki aryloxycarbonyl group, a force Rubamoiru group (the nitrogen atom of the group is the same or different and a hydrogen atom, an alkyl group, an optionally phenyl group is substituted be good benzyl group or substituted or substituted) or Chiokarubamoiru group

(The nitrogen atom of the group is the same or different and is substituted by a hydrogen atom, an alkyl group, an optionally substituted benzyl group or an optionally substituted phenyl group). ]

2-benzyloxy-1 7-oxabicyclo [4.1.0] heptane derivative.

5. according to Claim 1, R _u is hydrogen atom in the Izu Re one term selected from the range 2 and range 4 of claims claims, alkyl groups, alkenyl group, alkynyl group, alkoxyalkyl group, alkylthioalkyl group or An alkoxycarbonylalkyl group, wherein Ri2 is an acyl group, a haloalkylcarbonyl group, a cycloalkylcarbonyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an alkylsulfonyl group, or 2-benzyloxy-7-oxabicyclo [4.1.0] heptane derivatives which are an alkylsulfonyl group, a cycloalkylsulfonyl group, an optionally substituted benzylsulfonyl group, or an optionally substituted phenylsulfonyl group.

 6. A herbicide comprising, as an active ingredient, the 2-benzyloxy7-oxapicyclo [4.1.0] heptane derivative according to any one of claims 1 to 5.

 7. —General formula [V]

(Wherein, Rig represents an alkyl group or a benzyl group, R ₁₄ represents an alkyl group or an alkoxy group, and R ₁₅ has the same meaning as in claim 1 except for a formyl group or an optionally substituted benzyl group.) : Represents _7. ) A cyclohexenone derivative represented by the formula:

 8. General formula [VI]

(Wherein, R ₅ , R ₆ and R ₇ have the same meanings as in claim 1). 7-oxabicyclo [4.1.0] hepn-2-one derivative.

9. General formula [VII]

(Wherein, R ₁₃ and R ₁₄ each have the same meaning as described above, and R ₇ has the same meaning as in claim 1).

10. General formula [VIII]

(Wherein, R ₁₃ has the same meaning as described above, and R ₆ and R ₇ each have the same meaning as in claim 1.) 2-Hydroxy- ₇ -oxabicyclo [4.1.0] Heptane derivative.

11. General formula [IX]

(Wherein Ri R ₂ , R ₃ , R ₄ > R ₆ , and p each have the same meaning as in claim 1 and R ₁₃ has the same meaning as described above.) Xen derivatives.