JPH05208935A - Novel halogenated cycloalkanecarboxylic acid derivative, herbicide containing the same, and intermediate therefor - Google Patents

Abstract

PURPOSE:To produce a novel compound having a wide herbicidal spectrum, high herbicidal effect and high safety to the cropping plants. CONSTITUTION:A compound of formula I [X is halogen; (n) is 0 to 3; Z<1>, Z<2> are N, CH (not CH simultaneously); R<1> and R<2> are H, halogen, mono or dialkylamino, alkyl, alkoxy, alkylthio; A is O, N-B (B is OH, alkylcarbonyloxy, alkoxy; Y is H, OH, alkoxy, alkenoxy, alkinoxy, alkylthio, aryloxy, aralkyloxy, arylthio, pryidylthio, thienyloxy)] and salts thereof, for example, 1fluoro-(4,6- dimethoxypyrimidinyl-2-oxy)-1-cyclopentanecarboxylic aicd. The compound of formula I wherein A is O is obtained by reaction of a compound of formula II with a compound of formula III (U is halogen, etc.). The compounds of formula IV (V is H, alkyl, aralkyl, etc.) in which the compound of formula II is included are novel compounds.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel halogenated cycloalkanecarboxylic acid derivative, a herbicide containing it as an active ingredient, and an intermediate compound therefor.

[0002]

2. Description of the Related Art Alkanoic acids containing a pyrimidine ring or a triazine ring and herbicides containing the same are known as
For example, it is proposed in European Patent No. 346789-A and Japanese Patent Laid-Open No. 2-85262.

[0003]

However, the compounds described in the above-mentioned publicly known documents are still unsatisfactory in terms of herbicidal spectrum, amount of dropped drug, crop selectivity and the like.

Therefore, the inventors of the present invention have earnestly studied to develop a compound having a broader herbicidal spectrum, a higher herbicidal effect and a higher safety against cultivated crops than the compounds described in the above-mentioned known documents. As a result, the halogenated cycloalkanecarboxylic acid (or derivative thereof) having a halogenated position at a specific position and a halogenated cycloalkane having a pyrimidine ring or triazine ring having a substituent at a specific position bonded via an oxygen atom. The alkanecarboxylic acid derivative is novel, and it has been found that this compound exhibits excellent herbicidal activity not only on annual weeds but also on perennial weeds, and also shows high safety against certain cultivated crops. Was issued.

[0005]

Thus, according to the present invention, a halogenated cycloalkanecarboxylic acid derivative represented by the following general formula (I) and salts thereof are provided.

[0006]

[Chemical 6] In the formula, X represents a halogen atom, n represents an integer of 0 to 3, Z ¹ and Z ² are each a nitrogen atom or a group CH.
When Z ¹ is a nitrogen atom, Z ² represents a nitrogen atom or a group CH, and when Z ¹ is a group CH, Z ² represents a nitrogen atom. R ¹ and R ² are each independently hydrogen. An atom, a halogen atom, a mono- or di-lower alkyl-substituted amino, or in each case a lower alkyl, a lower alkoxy or a lower alkylthio optionally substituted by a halogen atom, A represents an oxygen atom or a group = N-B Where B is hydroxy, lower alkylcarbonyloxy or, in each case, lower alkoxy optionally substituted with hydroxycarbonyl or lower alkoxycarbonyl, Y is hydrogen atom, hydroxy, halogen atom in each case , Hydroxy, lower alkyl, lower alkoxy, lower alkylthio, lower alkoxycarbonyl, low Alkylcarbonyl, lower alkoxy optionally substituted with cyano, nitro or azido, lower alkenoxy, lower alkynoxy, lower alkylthio, aryloxy, aralkyloxy, arylthio, aralkylthio, lower cycloalkoxy, lower cycloalkenyloxy, pyridylthio, Furylmethyloxy, furylthio or thienyloxy, or azido, tri-lower alkyl [Wherein R ³ and R ⁴ each independently represent a hydrogen atom, lower alkyl, lower alkoxy, aryl or aralkyl, and R ³ and R ⁴ represent a lower cycloalkane ring together with the carbon atom to which they are bonded. R ⁵ and R ⁶ , which may be formed, are each independently a hydrogen atom,
Hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkenoxy, lower alkynoxy, lower alkylcarbonyloxy, cyano, lower alkylsulfonyl optionally substituted with a halogen atom, lower alkyl substituted with lower alkoxycarbonyl, Lower alkyl substituted with hydroxycarbonyl, lower alkoxy substituted with lower alkoxycarbonyl, lower alkoxy substituted with hydroxycarbonyl, halogen atom in each case, hydroxy, lower alkyl, lower alkoxy, lower substituted with halogen atom Alkyl, cyano, nitro, amino, mono or di-lower alkyl substituted aryl, aralkyl, aryloxy, optionally substituted with lower alkoxycarbonyl. Rarukiruokishi, arylcarbonyloxy, pyridyl,

[0007]

[Chemical 7] (Wherein Z ³ represents an oxygen atom, a group CH or a sulfur atom, Z ⁴ represents a nitrogen atom or a group CH, Z ¹ and Z ²
Means the same definition as above, and m is an integer of 0 or 1. (Wherein R ⁷ and R ⁸ are a hydrogen atom, lower alkyl, lower alkoxycarbonyl, lower alkyl substituted with lower alkoxycarbonyl, lower alkyl substituted with hydroxycarbonyl, or in each case a halogen atom, lower alkyl, Lower alkyl, lower alkoxy substituted with a halogen atom, aryl, aralkyl, pyridyl or benzothiazolyl optionally substituted with cyano, amino or nitro)]].

In the above general formula (I) of the present invention, X,
R¹, R², R³, R^Four, R^Five, R⁶, R⁷, R⁸, A and Y
Specific examples of atoms and groups in the definition of
It Halogen atom Fluorine, chlorine, bromine or iodine,Lower alkyl group ; For example, methyl, ethyl, n-pro
Pill, isopropyl, n-butyl, isobutyl, secondary
Chill, tert-butyl, n-pentyl, isopentyl, neo
Lower ones with 5 or less carbon atoms such as pentyl and tertiary pentyl groups
An alkyl group,Lower alkyl group substituted with halogen atom ; For example,
Monochloromethyl, trichloromethyl, trifluorome
Substituted with 1 to 3 halogen atoms, such as chill groups
Lower alkyl group,Lower alkoxy group ; For example, methoxy, ethoxy, n
-Propoxy, isopropoxy, n-butoxy, isobut
Number of carbon atoms such as toxy, secondary butoxy, tertiary butoxy groups, etc.
A lower alkoxy group of 5 or less,Lower alkoxy group substituted with halogen atom ;for example
For example, difluoromethoxy, trifluoromethoxy, 2-
Chloroethoxy, 2,2-dichloroethoxy, 2,2,2
-Trichloroethoxy, 2-bromoethoxy, 2-full
Oroethoxy, 2,2,2-trifluoroethoxy, 3-
1 to 3 halogens such as bromopropoxy group
A lower alkoxy group having 5 or less carbon atoms substituted with a nitrogen atom,Lower alkylthio group ; For example, methylthio, ethylthio
O, n-propylthio, isopropylthio, n-butyl
Thio, secondary butylthio, isobutylthio, tertiary butylthio
A lower alkylthio group having 5 or less carbon atoms such as an o group,Lower alkylthio group substituted with halogen atom ;for example
For example, difluoromethylthio, trifluoromethylthio,
2-chloroethylthio, 2,2-dichloroethylthio,
2,2,2-trichloroethylthio, 2-bromoethylthio
O, 2-fluoroethylthio, 2,2,2-trifluoro
From 1 such as ethylthio, 3-bromopropylthio group
Low C5 or less substituted with up to 3 halogen atoms
Primary alkylthio group,Mono or di-lower alkyl substituted amino group ; For example,
Methylamino, ethylamino, n-propylamino, a
Sopropylamino, n-butylamino, sec-butylami
No, isobutylamino, tert-butylamino, dimethylamino
Mino, diethylamino, di-n-propylamino, di-
Isopropylamino, ethylmethylamino, methylpro
Alkyl moieties such as pilamino groups with 5 or less carbon atoms
No or di-lower alkyl-substituted amino group,Lower alkylcarbonyloxy group ; For example, methyl carbonate
Rubonyloxy, ethylcarbonyloxy, n-propyi
Lucarbonyloxy, isopropylcarbonyloxy,
n-butylcarbonyloxy, isobutylcarbonylo
Xy, secondary butyl carbonyloxy, tertiary butyl carbo
Low carbon number of alkyl moiety such as nyloxy group is 5 or less
A carbonyloxy group to which a primary alkyl group is bonded,Lower alkoxy substituted with lower alkoxycarbonyl group
Shi group ; For example, methoxycarbonylmethoxy, etoki
Cycarbonylmethoxy, n-propoxycarbonylmeth
Xy, isopropoxycarbonylmethoxy, n-butoxy
Cicarbonyl methoxy, isobutoxy carbonyl meth
Ci, secondary butoxycarbonyl methoxy, tertiary butoxyca
Lubonylmethoxy, 1-methoxycarbonyl-ethoxy
Ci, 1-ethoxycarbonyl-ethoxy, 1-n-pro
Poxycarbonyl-ethoxy, 1-isopropoxyl
Bonyl-ethoxy, 1-n-butoxycarbonyl-eth
Xy, 1-isobutoxycarbonyl-ethoxy, 1-th
Dibutoxycarbonyl-ethoxy, 1-tertiary butoxyca
A lower alkyl group having a carbon number of 5 or less, such as rubonyl-ethoxy group.
A lower alkyl substituted with a carbonyl group to which a coxyl group is attached
Coxy group,Lower alkoxy group substituted with hydroxy ; For example,
2-hydroxyethoxy, 2-hydroxypropoxy,
3-hydroxypropoxy, 2-hydroxybutoxy,
3-hydroxybutoxy, 4-hydroxybutoxy, etc.
Such as a lower group substituted with a hydroxy group and having 5 or less carbon atoms.
Lucoxy group,Lower alkoxy substituted with hydroxycarbonyl group
Basis ; For example, hydroxycarbonylmethoxy, 1-hi
Hydroxy, such as droxycarbonyl-ethoxy group
Lower alkoxy having 5 or less carbon atoms substituted with a carbonyl group
Shi Ki,Lower alkoxycarbonyl group ; For example, methoxycar
Bonyl, ethoxycarbonyl, n-propoxycarbonyl
, Isopropoxycarbonyl, n-butoxycarbonyl
L, isobutoxycarbonyl, secondary butoxycarbonyl
And the alkyl moiety of tertiary butoxycarbonyl etc. is carbon
A lower alkoxycarbonyl group having a number of 5 or less,Lower alkenyl group ; For example, allyl group, 2-methyl-
2-propenyl group, 2-butenyl group, 3-butenyl group,
And a 3-methyl-2-butenyl group, etc., having 5 carbon atoms
The following lower alkenyl groups,Lower alkynyl group For example, 2-propynyl, and
Such as 2-butynyl and 3-butynyl groups having 5 or less carbon atoms
Lower alkynyl group,Lower alkylcarbonyl group ; For example, methylcarboni
L, ethylcarbonyl, n-propylcarbonyl, iso
Propylcarbonyl, n-butylcarbonyl, isobutyl
Lecarbonyl, secondary butylcarbonyl, tertiary butylcal
Lower alkyl having 5 or less carbon atoms in the alkyl moiety such as bonyl
Lecarbonyl,Optionally substituted aryl group ; For example, Feni
2-methylphenyl, 3-methylphenyl, 4-me
Tylphenyl, 2-chlorophenyl, 3-chlorophenyl
Ru, 4-chlorophenyl, 2-bromophenyl, 3-bu
Lomophenyl, 4-bromophenyl, 2-fluorophenyl
Nil, 3-fluorophenyl, 4-fluorophenyl,
2-nitrophenyl, 3-nitrophenyl, 4-nitro
Phenyl, 2-methoxyphenyl, 3-methoxyphenyl
4-methoxyphenyl, 2-trifluoromethylphenyl
Enyl, 3-trifluoromethylphenyl, 4-trif
Luoromethylphenyl, 2-aminophenyl, 3-ami
Nophenyl, 4-aminophenyl, 2-hydroxyphenyl
Nyl, 3-hydroxyphenyl, 2,3-dimethylphenyl
Nyl, 2,4-dimethyl phenyl, 2,5-dimethyl phenyl
Nyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl
Nyl, 3,5-dimethylphenyl, 2,3-dichlorophenyl
Nyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl
Nyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl
Nyl, 3,5-dichlorophenyl, 2,4-dinitrophenyl
Nyl, 2,6-dinitrophenyl, 3,4-dinitrophenyl
Nyl, 3,5-dinitrophenyl, 2,3,5-trichloro
Rophenyl, 2,4,6-trichlorophenyl, 1-naphth
Optionally substituted acetyl, 2-naphthyl group, etc.
Reel base,Aralkyl group which may be substituted ; For example, Benji
2-bromobenzyl, 3-bromobenzyl, 4-bu
Lomobenzyl, 2-chlorobenzyl, 3-chlorobenzyl
Ru, 4-chlorobenzyl, 2-fluorobenzyl, 3-
Fluorobenzyl, 4-fluorobenzyl, 2-methoxy
Cibenzyl, 3-methoxybenzyl, 4-methoxyben
Zil, 2-methylbenzyl, 3-methylbenzyl, 4-
Methylbenzyl, 2-nitrobenzyl, 3-nitroben
Even if it is substituted, such as dil, 4-nitrobenzyl group, etc.
Good aralkyl group,Lower alkenoxy group ; For example, vinyloxy, allyl
Oxy, 3-butenyloxy, 1-methyl-2-prope
Such as noxy, 2-methyl-2-propenyloxy group, etc.
Lower alkenoxy group having 5 or less carbon atoms,Lower alkynoxy group ; For example, 2-propynyloxy
Ci, 1-methyl-2-propynyloxy, 2-butynyl
C5 or more such as oxy or 3-butynyloxy group
Lower lower alkynoxy group,Optionally substituted aryloxy group ; For example,
Enoxy, naphthoxy, 2-bromophenoxy, 3-bu
Lomophenoxy, 4-bromophenoxy, 2-chlorophen
Enoxy, 3-chlorophenoxy, 4-chlorophenoxy
Ci, 2-methylphenoxy, 3-methylphenoxy, 4
-Methylphenoxy, 2-methoxyphenoxy, 3-me
Toxyphenoxy, 4-methoxyphenoxy, 2-nit
Rhophenoxy, 3-nitrophenoxy, 4-nitrophenol
Noxy group, etc.Aralkyloxy group which may be substituted ; For example,
Benzyloxy, 2-bromobenzyloxy, 3-bro
Mobenzyloxy, 4-bromobenzyloxy, 2-ku
Lolobenzyloxy, 3-chlorobenzyloxy, 4-
Chlorobenzyloxy, 2-fluorobenzyloxy,
3-fluorobenzyloxy, 4-fluorobenzylo
Xy, 2-methoxybenzyloxy, 3-methoxyben
Ziroxy, 4-methoxybenzyloxy, 2-methyl
Benzyloxy, 3-methylbenzyloxy, 4-methyl
Lubenzyloxy, 2-nitrobenzyloxy, 3-ni
Trobenzyloxy, 4-nitrobenzyloxy, 2,
4-dinitrobenzyloxy, 3,4-dinitrobenzyl
Luoxy, 3,5-dinitrobenzyloxy, 2,4,6
-Substituted such as trimethylbenzyloxy group
An aralkyloxy group, which may beOptionally substituted arylthio group ; For example, Hue
Nylthio, 2-bromophenyl, 3-bromophenyl
Ruthio, 4-bromophenylthio, 2-chlorophenyl
Thio, 3-chlorophenylthio, 4-chlorophenylthio
O, 4-fluorophenylthio, 2-methoxyphenyl
Thio, 3-methoxyphenylthio, 4-methoxyphenyl
Ruthio, 4-methylphenylthio, 4-nitrophenyl
An optionally substituted arylthio group such as a thio group,Aralkylthio group which may be substituted ; For example,
Benzylthio, 2-, 3- or 4-bromobenzylthio
O, 2-, 3- or 4-chlorobenzylthio, 2-,
3- or 4-fluorobenzylthio, 2-, 3-or
Is 4-methoxybenzylthio, 2-, 3- or 4-me
Cylbenzylthio, 3- or 4-nitrobenzylthio
An optionally substituted aralkylthio group, such asAn optionally substituted pyridylthio group ; For example, pili
Dil-2-thio, 5-nitropyridyl-2-thio group, etc.
An optionally substituted pyridylthio group,Lower cycloalkoxy group ; For example, cyclopropyl
Xy, cyclobutoxyloxy, cyclopentyl oxy
Si, cyclohexyloxy group,Lower cycloalkenyloxy group ;, For example, 2-cyclo
Pentenyloxy, 2-cyclohexenyloxy, 3-
A cyclohexenyloxy group,Furylmethyloxy group ; For example, 2-furylmethyl ester
Xy, 3-furylmethyloxy group,Furylmethylthio group ; For example, 2-furylmethylthio
O, 3-furylmethylthio group,Thienylmethyloxy group ; For example, 2-thienylmeth
Luoxy, 3-thienylmethyloxy group,Lower alkylsulfur which may be substituted with halogen atom
Honyl group ; For example, methanesulfonyl, ethanesulfo
Nyl, 1-propanesulfonyl, 2-propanesulfoni
1-butanesulfonyl, trichloromethanesulfoni
Le, trifluoromethanesulfonyl, 2,2,2-trif
1 or less, such as a fluoromethanesulfonyl group, having 5 or less carbon atoms
Up to 3 halogen atoms which may be substituted with halogen atoms
Primary alkylsulfonyl group,Optionally substituted arylcarbonyloxy group ；
For example, phenylcarbonyloxy, 2-chlorophenyl
Lecarbonyloxy, 3-chlorophenylcarbonylo
Xy, 4-chlorophenylcarbonyloxy, 2-tri
Fluoromethylphenylcarbonyloxy, 3-trif
Luoromethylphenylcarbonyloxy, 4-triflu
Oromethylphenylcarbonyloxy, 2,4-dichloro
Ruphenylcarbonyloxy, 2,6-dichlorophenyl
Lecarbonyloxy, 3,4-dichlorophenylcarbo
Nyloxy, 3,5-dichlorophenylcarbonyloxy
Ci, 2,4-dichloro-3-methylphenylcarbonyl
Arylcarbo which may be substituted such as oxy group
A nyloxy group,Benzothiazolyl group which may be substituted ; For example,
Benzothiazol-2-yl, 6-nitrobenzothiazo
Optionally substituted benzothia such as ol-2-yl group
Zolyl group.

The groups not specifically shown in the above groups are selected from the above atoms and groups in any combination or in accordance with the generally known common sense.

In the above general formula (I) of the present invention, when Y is a hydroxy group, a salt thereof is also included in the compound of the present invention. The salt is preferably an agriculturally acceptable salt, and examples thereof include alkali metal, ammonium or lower alkylammonium salts such as sodium, potassium, ammonium, isopropylammonium and triethylammonium.

One of the features of the halogenated cycloalkanecarboxylic acid derivative of the present invention is that X in the above-mentioned general formula (I) is a halogen atom. Since X is a halogen atom, the compound of the present invention has stronger herbicidal activity as compared with the compound in which X is a hydrogen atom.

In the general formula (I), X represents a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, preferably a fluorine atom or a chlorine atom, and most preferably a fluorine atom.

One of the other characteristics of the compound of the present invention is the group

[0014]

[Chemical 8] Is to have. This group can be specifically classified into the following three groups.

[0015]

[Chemical 9] Of these three groups, the preferred one is

[0016]

[Chemical 10] And particularly preferred is

[0017]

[Chemical 11] Is.

In the above three groups, R ¹ and R ² are selected from their preferable atoms or groups depending on whether the skeleton to which they are bound is pyrimidine or triazine. Ie

[0019]

[Chemical 12] In the case of, R ¹ and R ² are both lower alkoxy, R ¹ is lower alkoxy and R ² is a halogen atom, or R ¹ is a halogen atom and R ² is lower alkoxy. Preferably.

[0020]

[Chemical 13] In this case, it is preferred that both R ¹ and R ² are lower alkoxy. further

[0021]

[Chemical 14] In the case of, it is preferred that R ¹ is lower alkylthio and R ² is a halogen atom, especially a chlorine atom.

The compounds of the present invention have the general formula (I):
It is preferable that n has 0 or 1, that is, has a cyclopentane ring or a cyclohexane ring. Further, in the general formula (I), A is preferably an oxygen atom rather than the group = NB.

Y is hydroxy, lower alkoxy,
Lower alkenyloxy, lower alk Is either a hydrogen atom), preferably hydroxy, lower alkoxy, lower alkenyloxy, lower alkynyloxy or Examples of preferable halogen-containing compounds represented by the general formula (I) of the present invention include the following (1) to
It is as in (3).

(1) The following general formula (I) -i

[0026]

[Chemical 15] In the formula, R ¹ , R ² , X, Y and n have the same meanings as defined in the general formula (I), and are halogenated cycloalkanecarboxylic acid derivatives represented by

(2) The following general formula (I) -ii

[0028]

[Chemical 16] In the formula, R ¹ , R ² , X, Y and n have the same meanings as those in the general formula (I), and are halogenated cycloalkanecarboxylic acid derivatives represented by the formula:

(3) The following general formula (I) -iii

[0030]

[Chemical 17] In the formula, R ¹ , R ² , X, Y and n have the same meanings as defined in the general formula (I), and are halogenated cycloalkanecarboxylic acid derivatives represented by

According to the studies by the present inventors, the halogenated cycloalkanecarboxylic acid derivative represented by the general formula (I) is novel and has a strong herbicidal activity against many kinds of weeds. Was found.

Thus, according to the present invention, there is provided a herbicidal composition containing a halogenated cycloalkanecarboxylic acid derivative represented by the above general formula (I) as an active ingredient and an agrochemically acceptable diluent or carrier. To be done.

Further, according to the present invention, the above herbicidal composition is applied to the weeds or the environment in which the weeds are growing, or the environment in which the weeds are expected to grow, to eliminate the weeds or weeds. There is provided a method of inhibiting the development or growth of a.

The above herbicidal composition of the present invention and its application method will be described in detail later.

According to the studies by the present inventors, a compound represented by the following general formula (II) which can be a synthetic intermediate of the halogenated cycloalkanecarboxylic acid derivative represented by the above general formula (I) of the present invention having herbicidal activity is shown. It has been found that halogenated cycloalkanol derivatives are new. The halogenated cycloalkanol derivative is also included in the present invention.

That is, according to the present invention, the following general formula (I
I)

[0037]

[Chemical 18] In the formula, X, A, Y and n mean the same as defined in the general formula (I), V is a hydrogen atom, lower alkyl, lower alkylcarbonyl, lower alkylsulfonyl or
In each case aralkyl, arylcarbonyl optionally substituted with halogen atom, hydroxy, nitro, cyano, lower alkyl, lower alkoxy, halogen substituted lower alkyl, halogen substituted lower alkoxy, amino or mono- or di-lower alkyl substituted amino. Or, a halogen-containing cyclic compound represented by is represented by arylsulfonyl is provided.

The halogenated cycloalkanol derivative of the present invention represented by the general formula (II) has a halogen atom represented by X, and n is an integer from 0 to 3, that is, a 5- to 8-membered carbon. It is characterized by having a ring.

In the general formula (II), X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, preferably a fluorine atom or a chlorine atom, and particularly preferably a fluorine atom, and n is 0 or 1, that is, cyclo. A pentane ring or a cyclohexane ring is preferable.

In the general formula (II), Y has the same meaning as defined in the general formula (I), and as described above, the preferred ones in the general formula (I) are also preferred. ..

Further, in the general formula (II), V is a hydrogen atom, lower alkyl, lower alkylcarbonyl, lower alkylsulfonyl, aralkyl, arylcarbonyl or arylsulfonyl. Of these, aralkyl, arylcarbonyl and arylsulfonyl are
Those aromatic nuclei are optionally substituted by at least one of a halogen atom, hydroxy, nitro, cyano, lower alkyl, lower alkoxy, halogen substituted lower alkyl, halogen substituted lower alkoxy, amino or mono- or di-lower alkyl substituted amino. May be. Preferred as V is a hydrogen atom, aralkyl or arylcarbonyl.

The compounds of the present invention represented by the above general formulas (I) and (II) have two types of stereoisomers (cis and trans isomers) related to the saturated ring, and each of them is an optically active isomer. Can exist as

Hereinafter, the cis and trans designations indicate the relative steric configurations of the substituents adjacent to each other on the saturated ring, and a compound in which the 2-position substituent has a cis configuration based on the 1-position CAY group is referred to as a cis-form. ) A compound in which the 2-position substituent has a trans configuration based on the 1-position CAY group is referred to as a trans form (tra).
ns). When the corresponding compound is a racemic compound, a dextrorotatory compound, or a levorotatory compound, each is ra.
Displayed as c, +,-.

The specific compounds belonging to the halogenated cycloalkanecarboxylic acid derivative represented by the general formula (I) of the present invention are shown in Tables 1 to 4. Further, measured NMR analysis values and / or physical property data of some of the halogenated cycloalkanecarboxylic acid derivatives are shown in Tables 5 to 8.

Further, Table 9 shows specific compounds belonging to the halogenated cycloalkanol derivative represented by the general formula (II) of the present invention. Table 10 shows the measured NMR analysis values and / or physical property data of some of the halogenated cycloalkanol derivatives.

The meanings of the abbreviations used in Tables 1 to 4 and 9 are as follows. Ph represents a phenyl group.

Ph-2Cl, Ph-2OCH ₃ , Ph-
_{2NO 2, Ph-20C 2 H} 5, Ph-2CF 3, Ph-3
_{Cl, Ph-3OCH 3, Ph} -3NO 2, Ph-3OC
₂ H ₅ , Ph-3CF ₃ , Ph-4Cl, Ph-4OC
_{H 3, Ph-4NO 2,} Ph-4OC 2 H 5, Ph-4CF
₃ , Ph-2Br, Ph-2CH ₃ , Ph-3Br, Ph
-3CH _3, Ph-4Br, P in Ph-4CH _3, etc.
h represents a phenyl group, and the number part in "2Cl" etc. following Ph represents the substitution position with the phenyl ring, and Cl,
_{OCH 3, NO 2, OC 2} H 5, CF 3, Br, CH 3 and the like denotes a substituent bonded to the substitution position.

Ph-2,4-DiCl is a 2,4-dichlorophenyl group, Ph-2,6-DiCl is a 2,6-dichlorophenyl group, and Ph-3,4-DiCl is 3,4. -Dichlorophenyl group, Ph-3,5-DiCl represents 3,5-dichlorophenyl group, Ph-2,4-DiCl-3
CH ₃ shows the 2,4-dichloro-3-phenyl group.

Succinimidyl represents a 2,5-dioxo-1-pyrrolidinyl group.

[0050] O-N = C (- ( C 2 H 5) 5 -) is based on

[0051]

[Chemical 19] The _{show, C (- (C 2 H} 5) 5 -) represents a cyclohexyl group.

NH-2-thiadiazolyl 2-thiadiazol
yl is a 1,3,4-cyadiazol-2-yl group, NH-
2-thiadiazoly in 2-thiadiazolyl-5-CF ₃
l -5-CF ₃ denotes a 5-trifluoromethyl-1,3,4-thiadiazol-2-yl group.

[0053]

[Table 1]

[0054]

[Table 2]

[0055]

[Table 3]

[0056]

[Table 4]

[0057]

[Table 5]

[0058]

[Table 6]

[0059]

[Table 7]

[0060]

[Table 8]

[0061]

[Table 9]

[0062]

[Table 10] The compounds of the present invention can be prepared by the following methods (method B-1 and B-2).
Method, B-3 Method, B-4 Method, B-5 Method, A-1 Method, A-2
Method, A-3 method, A-4 method, A-5 method), or is not limited to these methods.

1. Preparation of compound represented by general formula (II)
Construction method B-1 method

[0064]

[Chemical 20] [In the formula, Y, X and n have the same meanings as described above. In the above reaction formula, the compound represented by the formula (II-a) is obtained by using the halogenated cycloalkanone derivative of the above formula (III) in the presence of a solvent without a solvent or a suitable base, It can be produced by reacting with various reducing agents in the temperature range of 78 ° C. to the boiling point of the solvent for 1 to 24 hours.

When a solvent is used in this reaction, examples thereof include alcohol solvents such as methanol, ethanol and isopropyl alcohol; hydrocarbon solvents such as benzene, toluene and xylene; halogenation of dichloromethane, chloroform and the like. Hydrocarbon solvents;
Ethereal solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane;
Examples thereof include ketone solvents such as acetone and methyl ethyl ketone; ester solvents such as methyl acetate and ethyl acetate; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, dimethylacetamide; acetonitrile, water and the like.

As the reducing agent, organic tin compounds such as triphenyl tin hydride, diphenyl tin hydride, tri-n-butyl tin hydride, di-n-butyl tin hydride, tri-t-butyl aluminum lithium hydride, hydrogen Sodium borohydride, Sodium trimethoxyborohydride, Sodium borohydride, Sodium borohydride, Lithium borohydride, Calcium triethylborohydride, Potassium borohydride, Potassium triisopropoxyborohydride, Trihydrated tri- s
-Metal hydrogen complex compounds such as potassium butyl borohydride, zinc borohydride, tetramethylammonium borohydride, cyanoborohydride tetra-n-butylammonium or related compounds, diborane or dimethylamine-
Borane complexes such as borane complex, trimethylamine-borane complex, triethylamine-borane complex, t-butylamine-borane complex, pyridine-borane complex, dimethylsulfide-borane complex, morpholine-borane complex, 1,4-oxathian-borane complex , Dicyclohexylborane, alkylboranes such as 9-borabicyclo [3,3,1] nonane, metal alkoxides such as isopropoxyaluminum, tert-butyluminium, catalytic hydrogenation catalysts such as palladium carbon, platinum oxide, Raney-Nitzkel You can

The fluorinated cycloalkanone derivative of the above-mentioned formula (III) which is a raw material is, for example, tetrahedron.
Letters 27, 37, 4465 pages-4468
It can be manufactured by referring to the method described on page (1986).

Method B-2

[0069]

[Chemical 21] [In the formula, Y and n have the same meanings as described above, V'has the same meaning as V described above, but a hydrogen atom is excluded. X represents a halogen atom. ] In the above reaction formula, in the formula (II
The compound represented by the formula (b) is obtained by using the halogenated cycloalkanol derivative of the above formula (II-a) without a solvent or in the presence of a suitable solvent with a suitable base at a temperature of -78 ° C to the boiling point of the solvent. In the range, it can be produced by reacting with a compound represented by V'-X for 1 to 24 hours. When a solvent is used in this reaction, for example, a hydrocarbon solvent such as benzene, toluene, or xylene; a halogenated hydrocarbon solvent such as dichloromethane or chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran,
Or ether solvent such as 1,4-dioxane; ketone solvent such as acetone or methyl ethyl ketone; ester solvent such as methyl acetate or ethyl acetate; aprotic polar solvent such as dimethylformamide, dimethylsulfoxide or dimethylacetamide Acetonitrile, water, etc. can be mentioned.

As the base, carbonates such as sodium carbonate or potassium carbonate; metal hydroxides such as sodium hydroxide or potassium hydroxide; metal alcoholates such as sodium methylate or sodium ethylate; hydrogen. Examples thereof include alkali metal hydrides such as sodium hydride and potassium hydride; lithium amides such as lithium diethylamide, lithium diisopropylamide, and lithium bistrimethylsilylamide.

Method B-3

[0072]

[Chemical formula 22] [Wherein Y, X, V and n have the same meanings as described above,
M represents an alkali metal, alkaline earth metal, or alkaline earth metal cation. ] In the above reaction formula, in the formula (II
The compound of the formula (c) is produced by reacting the compound of the formula (II-e) with a suitable base in the presence of a suitable solvent at room temperature to the boiling point of the solvent for 1 to 24 hours. be able to. In addition, the formula (II-
The compound of formula (I
A compound represented by Id) can be produced. Examples of the solvent used in this reaction include alcohol solvents such as methanol, ethanol, or isopropyl alcohol; hydrocarbon solvents such as benzene, toluene, or xylene; halogenated hydrocarbon solvents such as dichloromethane or chloroform. Diethyl ether, diisopropyl ether, tetrahydrofuran,
Or an ether solvent such as 1,4-dioxane; a ketone solvent such as acetone or methyl ethyl ketone; an ester solvent such as methyl acetate or ethyl acetate; an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide, or methylacetamide Acetonitrile, water, etc. can be mentioned. Examples of the base include sodium carbonate, potassium carbonate, carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate. An alkali metal hydride such as sodium hydride or potassium hydride.

Method B-4

[0074]

[Chemical formula 23] [In the formula, Y, X, V and n have the same meanings as described above.
R represents a group which can be converted into Y in this reaction, and T represents a hydroxyl group, a mercapto group, an amino group or a halogen atom. In the above reaction formula, the compound represented by the formula (II-e) is a hydroxyl group represented by RT, a mercapto group or an amino group represented by the formula (II-d) using a suitable condensing agent. Alternatively, it can be produced by reacting a compound having a halogen atom with or without a solvent in the presence of a solvent under ice-cooling or in the temperature range of the boiling point of the solvent for 1 to 24 hours. As the solvent used in the reaction, benzene,
Hydrocarbon solvents such as toluene or xylene; halogenated hydrocarbon solvents such as dichloromethane, chloroform; diethyl ether, diisopropyl ether,
Ether-based solvent such as tetrahydrofuran or 1,4-dioxane; Ketone-based solvent such as acetone or methyl ethyl ketone; Ester-based solvent such as methyl acetate or ethyl acetate; Aprotic such as dimethylformamide, dimethylsulfoxide or dimethylacetamide A polar solvent; acetonitrile, water, etc. can be mentioned.

As the condensing agent, carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate or potassium hydrogen carbonate; metal hydroxides such as sodium hydroxide or potassium hydroxide; sodium methylate or sodium ethyl ester. Examples thereof include metal alcoholates such as salts; alkali metal hydrides such as sodium hydride or potassium hydride; organic bases such as diazabicycloundecene; and dehydration condensing agents such as dicyclohexylcarbodiimide.

Method B-5

[0077]

[Chemical formula 24] [In the formula, Y, X and n have the same meanings as described above. V ″
Represents a lower alkoxycarbonyl group, a lower alkylsulfonyl group or an optionally substituted arylsulfonyl group. In the above reaction scheme, the compound represented by the formula (II-e) is obtained by reacting the carboxylic acid represented by the formula (II-d) with a suitable activator represented by V ″ -Cl in the presence of a suitable base. It can be produced by once reacting with the corresponding alcohol, amine or thiol in the presence of a catalyst or a catalyst, after being converted into an active intermediate, and the solvent used in the reaction is, for example, benzene, toluene, or xylene. , Etc., hydrocarbon solvents such as dichloromethane, or halogenated hydrocarbon solvents such as chloroform; ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, or 1,4-dioxane;
Ketone-based solvents such as acetone or methionyl ethyl ketone; ester-based solvents such as methyl acetate or ethyl acetate; aprotic polar solvents such as dimethylformamide, dimethyl sulfoxide, or dimethylacetamide;
Acetonitrile, water, etc. can be mentioned.
Examples of the base include pyridine, organic bases such as triethylamine, and activators include methyl chloroformate, methyl chloroformate such as ethyl chloroformate, or alkyl chloroformates such as ethyl chloroformate; benzenesulfonyl chloride, Alternatively, arylsulfonyl chlorides such as toluenesulfonyl chloride and the like can be mentioned. Examples of the catalyst include dimethylaminopyridine, 4-pyrrolidinopyridine and the like.

2. Production of compound represented by general formula (I)
Method A-1 method

[0079]

[Chemical 25] [In the formula, Y, X, R ¹ , R ² , Z ¹ , Z ² and n have the same meanings as described above, and U represents a halogen atom, a lower alkylsulfonyl group or an arylalkylsulfonyl group. In the reaction formula of the above Method A, the compound represented by the formula (I ′) is the halogenated cycloalkanol derivative of the above formula (II) in the presence of no solvent or a suitable solvent, using a suitable base, It can be produced by reacting with the substituted pyrimidine or triazine of the above formula (IV) in the temperature range of −78 ° C. to the boiling point of the solvent for 1 to 24 hours.

When a solvent is used in this reaction, examples thereof include hydrocarbon solvents such as benzene, toluene or xylene; halogenated hydrocarbon solvents such as dichloromethane or chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran. Or an ether solvent such as 1,4-dioxane; a ketone solvent such as acetone or methyl ethyl ketone; an ester solvent such as methyl acetate or ethyl acetate; an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide or dimethylacetamide; acetonitrile or Water etc. can be mentioned.

As the base, carbonates such as sodium carbonate or potassium carbonate; metal hydroxides such as sodium hydroxide or potassium hydroxide; metal alcoholates such as sodium methylate or sodium ethylate; sodium hydride or Examples thereof include alkali metal hydrides such as potassium hydride; lithium amides such as lithium diethylamide, lithium diisopropylamide and lithium bistrimethylsilylamide.

Method A-2

[0083]

[Chemical formula 26] [In the formula, Y, X, T, R ¹ , R ² , Z ¹ , Z ² and n have the same meanings as described above, and R represents a group which can be converted to Y in this reaction. In the above reaction formula, the compound represented by the formula (Ib) is a hydroxyl group represented by RT, a mercapto group, or an amino group represented by the formula (Ia) using a suitable condensing agent. Alternatively, it can be produced by reacting a compound having a halogen atom with or without a solvent in the presence of a solvent under ice-cooling or in the temperature range of the boiling point of the solvent for 1 to 24 hours. Examples of the solvent used in the reaction include hydrocarbon solvents such as benzene, toluene and xylene; halogenated hydrocarbon solvents such as dichloromethane and chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran, and ethers such as 1,4-dioxane. System solvents; acetone or ketone solvents such as methyl ethyl ketone; ester solvents such as methyl acetate or ethyl acetate; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, dimethylacetamide; acetonitrile, water, etc. You can As the condensing agent, sodium carbonate,
Carbonates such as potassium carbonate, sodium hydrogen carbonate, or potassium hydrogen carbonate; metal hydroxides such as sodium hydroxide or potassium hydroxide; metal alcoholates such as sodium methylate or sodium ethylate; sodium hydride, or Examples thereof include alkali metal hydrides such as potassium hydroxide; organic bases such as diazabicycloundecene; and dehydration condensation agents such as dicyclohexylcarbodiimide.

Method A-3

[0085]

[Chemical 27] [Wherein Y, X, R ¹ , R ² , Z ¹ , Z ² and n have the same meanings as described above, and V is a lower alkoxycarbonyl group, a lower alkylsulfonyl group or an optionally substituted arylsulfonyl group. Indicates. In the above reaction scheme, the compound of formula (Ib) is obtained by reacting the carboxylic acid of formula (Ia) with a suitable activator represented by V-Cl in the presence of a suitable base. It can be produced by once converting to an active intermediate and then reacting with a corresponding alcohol, amine or thiol in the presence of a catalyst or a catalyst. Examples of the solvent used in the reaction include hydrocarbon solvents such as benzene, toluene, or xylene; halogenated hydrocarbon solvents such as dichloromethane or chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran, or 1,4-dioxane. Ether solvent such as acetone; ketone solvent such as acetone or methyl ethyl ketone; ester solvent such as methyl acetate or ethyl acetate; aprotic polar solvent such as dimethylformamide, dimethylsulfoxide, dimethylacetamide; acetonitrile, water, etc. Can be mentioned. Examples of the base include pyridine, organic bases such as triethylamine, and activators include methyl chloroformate, alkyl chloroformates such as ethyl chloroformate, benzenesulfonyl chloride, or arylsulfonyl chloride such as toluenesulfonyl chloride. Can be mentioned. As a catalyst, dimethylaminopyridine, or 4-
Examples thereof include pyrrolidinopyridine.

Method A-4

[0087]

[Chemical 28] [In the formula, X, Y, R ¹ , R ² , Z ¹ , Z ² , n and M have the same meanings as described above. ] In the above reaction formula, in the formula (I-
The compound represented by the formula (c) can be produced by reacting the compound represented by the formula (Ib) with a suitable base in the presence of a suitable solvent at room temperature to the boiling point of the solvent for 1 to 24 hours. You can In addition, the compound represented by formula (Ia) can be produced by treating the compound represented by formula (Ic) with an acid. Examples of the solvent used in this reaction include alcohol solvents such as methanol, ethanol, or isopropyl alcohol; hydrocarbon solvents such as benzene, toluene, or xylene; halogenated hydrocarbon solvents such as dichloromethane or chloroform. Diethyl ether, diisopropyl ether, tetrahydrofuran, or 1,
An ether solvent such as 4-dioxane; a ketone solvent such as acetone or methyl ethyl ketone; an ester solvent such as methyl acetate or ethyl acetate; an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide, or dimethylacetamide; acetonitrile, Alternatively, water or the like can be used. As the base, carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, or potassium hydrogen carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal alcoholates such as sodium methylate or sodium ethylate. Examples thereof include alkali metal hydrides such as sodium hydride and potassium hydride.

[0088] When R ⁶ represents hydrogen, the substituent R ⁷ can be introduced by the following Method A-5.

Method A-5

[0090]

[Chemical 29] [In the formula, Z ¹ , Z ² , R ¹ , R ² , R ⁵ , R ⁶ and n have the same meanings as described above, and R ⁷ represents a lower alkyl group. In the reaction formula of the above-mentioned Method A-5, the compound represented by the formula (Ie) is the amide derivative of the above formula (Id) in the absence of a solvent or in the presence of a suitable solvent. Can be produced by reacting with various alkylating agents in the temperature range of -78 ° C below freezing to the boiling point of the solvent for 1 to 24 hours.

When a solvent is used in this reaction, examples thereof include hydrocarbon solvents such as benzene, toluene and xylene; halogenated hydrocarbon solvents such as dichloromethane and chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran. 1,4-
Ether solvents such as dioxane; ketone solvents such as acetone and methyl ethyl ketone; ester solvents such as methyl acetate and ethyl acetate; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, dimethylacetamide; acetonitrile, water, etc. You can

As the base, carbonates such as sodium carbonate and potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; sodium hydride. Examples thereof include alkali metal hydrides such as potassium hydride; lithium amides such as lithium diethylamide, lithium diisopropylamide and lithium bistrimethylsilylamide.

Further, methyl iodide as an alkylating agent,
Lower halogenated alkyls such as methyl bromide, ethyl iodide and ethyl bromide, diazoalkanes such as diazomethane and diazoethane, sulfonic acid esters such as methyltrifluoromethanesulfonate, ethyltrifluoromethanesulfonate and methylfluorosulfonate. And alkyloxonium salts such as trimethyloxonium tetrafluoroborate and triethyloxonium tetrafluoroborate.

Method A-6

[0095]

[Chemical 30] [In the formula, X, n, Z ¹ , Z ² and R ¹ , R ² have the same meanings as described above, and E represents a racemic or optically active organic amine. ] In the above reaction formula, the formula (rac)-
The salt of (If) can be produced by reacting (Ia) with a suitable organic base E in the presence of a suitable solvent in the temperature range of room temperature to the boiling point of the solvent. This salt is again (rac)-by reacting with a suitable acid.
It can be led to (Ia).

The racemic compound represented by the above formula (rac)-(Ia) is reacted with a suitable optically active organic amine E in the presence of a suitable solvent in the temperature range from room temperature to the boiling point of the solvent. To give a mixture of diastereomeric salts,
Then, the mixture is recrystallized in a suitable solvent in the temperature range of room temperature to the boiling point of the solvent and purified to produce the optically active salt (If). Further, this salt is decomposed with a suitable acid in the presence of a suitable solvent at room temperature to the boiling point of the solvent to give (+)
-Or (-)-(Ia) can be produced.

When a solvent is used in this reaction, examples thereof include hydrocarbon solvents such as benzene, toluene and xylene; halogenated hydrocarbon solvents such as dichloromethane and chloroform; diethyl ether, diisopropyl ether, tetrahydrofuran. 1,4-
Ether-based solvents such as dioxane; ketone-based solvents such as acetone and methyl ethyl ketone; ester-based solvents such as methyl acetate and ethyl acetate; aprotic polar solvents such as dimethylformamide, dimethyl sulfoxide, dimethylacetamide; methyl alcohol, ethyl alcohol, normal Examples thereof include alcohol solvents such as propyl alcohol, isopropyl alcohol and tert-butyl alcohol; acetonitrile and water.

As the amine, ammonia, methylamine, ethylamine, normal propyl amine, isopropyl amine, normal butyl amine, secondary butyl amine, tertiary butyl amine, normal hexyl amine, normal octyl amine, normal nonyl amine, normal decyl amine and the like are used. Alkylamines; Brucine, Cinchonidine, Cinchonine, Dehydroabietylamine, 1
-(Phenylethylamine, morphine, deoxyefedrin, strychnine, quinine, amphetamine, threo-2-amino-1-paranitrophenyl-1,3-propanediol, or 1- (1-naphthyl) ethylamine (+ ) -Form or (-)-form organic amines can be mentioned.

Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid.

Next, synthetic examples of the compounds belonging to the above formulas (II) and (I) of the present invention will be explained with reference to examples.

[0101]

EXAMPLES Example 1 1-Fluoro-2-hydroxy-1-cyclo
Pentanecarboxylic acid methyl ester cis form (compound number
Production of No. 2a): First, Tetrahedron Letters Vol. 27, No. 37, 4
Methyl 1-fluoro-2-oxocyclopentanecarboxylate was produced from methyl 2-oxocyclopentanecarboxylate with reference to the method described on pages 465 to 4468 (1986). Then dry diglyme 50
2.3 ml of trimethylamine-borane complex (0.0 ml) in ml.
32 mol) and 5.0 g (0.031 mol) of methyl 1-fluoro-2-oxocyclopentanecarboxylate described above.
The solution added with was cooled to 0 ° C., and while stirring in a nitrogen stream, boron trifluorolide etherate 0.8 m
1 was added dropwise. After stirring the solution at room temperature for 1 hour,
The mixture was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ether. The ether layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain the cis form of the target methyl 1-fluoro-2-hydroxycyclopentanecarboxylate containing almost no trans form (Compound No. 2a; 1-position methoxy). This yielded 4.5 g (yield: 89%) of a substance whose 2-position substituent had a cis configuration based on the carbonyl group.

¹ H-NMR (δ, CDCl ₃ ): 1.33
-3.03 (6H, m), 3.82 (3H, s), 4.0
7-4.60 (1 H, m) ppm.

Example 2 1-Fluoro-2-hydroxy
-1-Cyclopentanecarboxylic acid methyl ester tiger
Preparation of the compound (Compound No. 2b); at room temperature under nitrogen flow, 3.1 ml (0.031 mol) of dimethylsulfide-borane complex was added to 50 ml of dry tetrahydrofuran. The solution was cooled to 0 ° C. and 1-fluoro-2-synthesized according to the literature given in Example 1.
Oxocyclopentanecarboxylic acid methyl ester 5.0
g (0.031 mol) was added dropwise. After stirring at room temperature for 1 hour, the solvent was distilled off, the residual liquid was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the cis-form of methyl 1-fluoro-2-hydroxycyclopentanecarboxylate (Compound No. 2a; based on the 1-position methoxycarbonyl group) Substances presumed to have the trans configuration of the 2-position substituent)
And a trans isomer (compound No. 2b; a substance whose 2-position substituent is presumed to have a trans configuration based on the 1-position methoxycarbonyl group) 3.
7 g (yield: 73%) was obtained. As a result of analysis by gas chromatography, the cis / trans generation ratio was 9/91, but this mixture was further subjected to silica gel column chromatography (developing solvent; hexane / ethyl acetate = 1.
0: 1) to obtain 3.3 g (yield: 65%) of the desired trans form of methyl 1-fluoro-2-hydroxycyclopentanecarboxylate (Compound No. 2b).

¹ H-NMR (δ, CDCl ₃ ): 1.30
-2.90 (6H, m), 3.80 (3H, s), 4.0
3-4.63 (1H, m) ppm.

Example 3 1-Fluoro-2-hydroxy
Cis of -1-cyclohexanecarboxylic acid ethyl ester
Body and trans form (compound numbers 73a, 73b)
Concrete; Under a nitrogen stream, at room temperature, dimethyl sulphates id - was added borane complex 3.1ml of (0.031 mol) in dry tetrahydrofuran 50 ml. The solution was cooled to 0 ° C. and 1-fluoro-2-oxocyclohexanecarboxylic acid ethyl ester synthesized according to the method of Example 1 5.8 g (.0.
(031 mol) was added dropwise. After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure, the residual liquid was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off to give the cis form of 1-fluoro-2-hydroxycyclohexanecarboxylic acid ethyl ester (Compound No. 73a; based on the 1-position ethoxycarbonyl group). A substance in which the 2-position substituent is assumed to have a trans configuration) and a trans form (Compound No. 73b; 1)
This gave 4.3 g (yield: 85%) of a stereoisomer mixture consisting of a substance in which the 2-position substituent had a trans configuration based on the position ethoxycarbonyl group. This mixture was further purified by silica gel column chromatography (developing solvent; hexane / ethyl acetate = 10: 1) to give the desired cis-form of 1-fluoro-2-hydroxycyclopentanecarboxylic acid methyl ester (compound No. 73).
a) 1.6 g (yield: 27.2%) and trans isomer (Compound No. 73b) 2.4 g (yield: 40.7%) were obtained.

Example 4 ; 1-Fluoro-2-hydroxy
Cis of 1-cycloheptanecarboxylic acid methyl ester
Body and trans form (Compound Nos. 134a and 134b)
Manufacture of; was first synthesized 1-fluoro-2-oxo-1-cycloheptanecarboxylic acid methyl ester of starting material in the following manner to literature methods shown in Example 1 as a reference. Sodium hydride (60% in 45 ml dry tetrahydrofuran)
0.88 g (22 mmol) of a suspension in mineral oil)
While stirring in the range of -5 ℃ ~ 0 ℃ 3.4g (20mm
ol) 2-oxocycloheptanecarboxylic acid methyl ester was added dropwise. When the generation of hydrogen gas stops, N
5.8 g (20 mmol) of -fluoro-2,4,6-trimethylpyridinium triflate was added, the temperature was returned to room temperature, and stirring was continued for 2 hours. Tetrahydrofuran was distilled off, the contents were poured into a 1N dilute hydrochloric acid aqueous solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was thoroughly washed with a dilute hydrochloric acid aqueous solution, and further washed successively with a saturated saline solution, a saturated sodium hydrogen carbonate aqueous solution, and a saturated saline solution. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the starting material, 1-fluoro-2-oxo-1-cycloheptanecarboxylic acid methyl ester 2.
63 g (yield: 70%) was obtained.

25 ml of methanol was cooled to 5 ° C., and 70 mg (1.8 mmol) of sodium hydroxide and 0.14 g (3.7 mmol) of sodium borohydride were added. Into this solution, 1-fluoro-2-
2.5 g (13.3 mmol) methanol solution of oxo-1-cycloheptanecarboxylic acid methyl ester (10 ml) was added dropwise. After stirring at room temperature for 2 hours, the contents were poured into saturated saline and extracted with ethyl acetate. The extract was washed successively with dilute hydrochloric acid, brine, saturated aqueous sodium hydrogen carbonate solution and brine. The ethyl acetate layer was dried over anhydrous sodium sulfate and the solvent was distilled off to obtain 2.3 g of a crude product. This was purified by silica gel column chromatography (developing solvent: hexane / isopropyl alcohol = 99/1), and 1
-Fluoro-2-hydroxycycloheptanecarboxylic acid methyl ester cis form (Compound No. 134a; a substance presumed to have a cis configuration at the 2-position substituent based on the 1-position methoxycarbonyl group) 1.4 g (yield Rate: 55.4
%) ¹ H-NMR (δ, CDCl ₃ ): 0.98-2.62 (1
0H, m), 3.80 (3H, s), 3.88-4.35
(1H, m) ppm.

And the trans form (Compound No. 134b;
0.6 g (yield: 23.7%) of a substance in which the 2-position substituent is assumed to have the trans configuration based on the 1-position methoxycarbonyl group was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.18
-2.75 (10H, m), 3.78 (3H, s), 3.
90-4.40 (1H, m) ppm.

Example 5 ; 1-Fluoro-2-hydroxy
-1-Cyclooctanecarboxylic acid ethyl ester (Compound
No. 153); organosynthesis, ethyl oxo-2-cyclooctanecarboxylate from cyclooctanone according to the method described in Collective Volume 5, page 198 (1973). The ester was synthesized. This was fluorinated and reduced by the same method as in Example 4 to 1
Cis-form of fluoro-2-hydroxycyclooctanecarboxylic acid ethyl ester (substance in which it is presumed that the 2-position substituent has a cis configuration based on the 1-position methoxycarbonyl group) and trans form (1-position methoxycarbonyl group) A mixture of (substances presumed to have the trans configuration of the 2-position substituent based on the above) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.35
-2.87 (12H, m), 1.30 (3H, t, J =
7.0 Hz), 3.80-4.40 (1H, m), 4.25
(2H, q, J = 7.0 Hz) ppm.

Example 6 ; 2-acetoxy-1-fluoro
Cis of -1-cyclopentanecarboxylic acid methyl ester
Production of body (Compound No. 3a); 1-fluoro-2-hydroxy-1 synthesized in Example 1
-To 0.5 g (3 mmol) of cis-form of cyclopentanecarboxylic acid methyl ester (Compound No. 2a), 0.32 g (3 mmol) of acetic anhydride and a catalytic amount of concentrated sulfuric acid were added at room temperature, and the mixture was stirred for 5 hours. The reaction mixture was poured into ice water, extracted with ethyl acetate, and washed successively with saturated brine, saturated aqueous sodium hydrogen carbonate solution and saturated brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the target cis isomer of 2-acetoxy-1-fluoro-1-cyclopentanecarboxylic acid methyl ester (Compound No. 3a) was obtained.
0.45 g (yield: 72%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.50
-2.93 (6H, m), 2.02 (3H, s), 3.7
7 (3H, s), 5.00-5.50 (1H, m) pp
m.

Example 7 ; 2-benzoyloxy-1-ph
Luoro-1-cyclopentanecarboxylic acid methyl ester
Of the cis-form (Compound No. 4a) of 1-fluoro-2-hydroxy-1 synthesized in Example 1
In a mixture of 0.5 g (3 mmol) of cis-form of cyclopentanecarboxylic acid methyl ester (Compound No. 2a) and 2 ml of pyridine, under ice-cooling, 0.1% of benzoyl chloride was added.
45 g (3 mmol) was added, the mixture was returned to room temperature and stirred for 5 hours. The reaction solution was poured into a dilute hydrochloric acid aqueous solution, extracted with ethyl acetate, and washed successively with saturated saline, saturated sodium hydrogen carbonate aqueous solution, and saturated saline. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain the desired cis-isomer of 2-benzoyloxy-1-fluoro-1-cyclopentanecarboxylic acid methyl ester (Compound No. 4a) 0.68.
g (yield: 84%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.47
-3.03 (6H, m), 3.73 (3H, s), 5.2
0-5.73 (1H, m), 7.20-8.22 (5H,
m) ppm.

Example 8 1-Fluoro-2-methanesulfur
Methyl phenyloxy-1-cyclopentanecarboxylate
Production of cis ster compound (Compound No. 5a); 1-fluoro-2-hydroxy-1 synthesized in Example 1
-To a mixture of 0.5 g (3 mmol) of cis-form of cyclopentanecarboxylic acid methyl ester (Compound No. 2a) and 2 ml of pyridine, 0.36 g (3 mmol) of methanesulfonyl chloride was added under ice cooling and stirred at 0 ° C for 5 hours. did. The reaction solution was poured into ice water, extracted with ether, and washed with cold water. The ether layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and 0.59 g of the desired cis-isomer of 2-methanesulfonyloxy-1-fluoro-1-cyclopentanecarboxylic acid methyl ester (compound No. 5a) was obtained (yield : 80%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.52
-2.63 (6H, m), 3.00 (3H, s), 3.8
1 (3H, s), 4.80-5.28 (1H, m) pp
m.

Example 9 ; 1-Fluoro-2-paratoluene
Sulfonyloxy-1-cyclopentanecarboxylic acid
Production of cis ester of tyl ester (Compound No. 6a); 1-fluoro-2-hydroxy-1 synthesized in Example 1
-To a mixture of 0.5 g (3 mmol) of cis-form of cyclopentanecarboxylic acid methyl ester (Compound No. 2a) and 2 ml of pyridine, 0.56 g (3 mmol) of paratoluenesulfonyl chloride was added under ice cooling, and the mixture was returned to room temperature to give 5 Stir for hours. The reaction solution was poured into ice water, extracted with ether, and washed with cold water. The ether layer is dried over anhydrous magnesium sulfate, the solvent is distilled off, and the desired cis-form of 2-paratoluenesulfonyloxy-1-fluoro-1-cyclopentanecarboxylic acid methyl ester (Compound No. 6
a) 0.77 g (yield: 79%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.37
-2.37 (6H, m), 2.46 (3H, s), 3.7
0 (3H, s), 4.27-5.17 (1H, m), 7.
00-8.20 (5H, m) ppm.

Example 10 ; 1-Fluoro-2-methoxy
-1-Cyclopentanecarboxylic acid methyl ester tiger
Preparation of a derivative (compound No. 13b); sodium hydride (60% suspension in mineral oil) 0.12 g
(3 mmol) was added to 5 ml of dry dimethyl sulfoxide and cooled to 5 ° C. To this solution, the trans form of 1-fluoro-2-hydroxy-1-cyclopentanecarboxylic acid methyl ester synthesized in Example 2 (Compound No. 2
b) 0.5 g (3 mmol) of dimethyl sulfoxide solution (5 ml) was added dropwise, and methyl iodide (0.47 g) (3.3 mmo) was added.
1) was added, the mixture was returned to room temperature and stirred for 2 hours. The reaction solution was poured into a dilute hydrochloric acid aqueous solution, extracted with ethyl acetate, and washed successively with saturated saline, saturated aqueous sodium hydrogen carbonate solution and saturated saline. The ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was evaporated, and the target 2-methoxy-1-fluoro-1-cyclopentanecarboxylic acid methyl ester trans form (Compound No. 13b) (0.33 g) was obtained. 62
%) Was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.42
-2.68 (6H, m), 3.35 (3H, s), 3.8
0 (3H, s), 4.03 to 5.00 (1H, m) pp
m.

Example 11 ; 1-Fluoro-2-methoxy
Trans form of -1-cyclopentanecarboxylic acid (compound
No. 12b); 1-fluoro-2-methoxy-1 synthesized in Example 10
-Trans-form of cyclopentanecarboxylic acid methyl ester (Compound No. 13b) (0.35 g, 2 mmol) was dissolved in methanol (5 ml), 5% aqueous potassium hydroxide solution (8 ml) was added, and the mixture was stirred at room temperature for 2 hr. The reaction solution was poured into a dilute aqueous hydrochloric acid solution, extracted with ether, the ether layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain the desired 2
0.26 g (yield: 81%) of trans form of methoxy-1-fluoro-1-cyclopentanecarboxylic acid (Compound No. 12b) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.43
-2.60 (6H, m), 3.43 (3H, s), 3.7
7-4.67 (1H, m), 8.47 (1H, s) pp
m.

Example 12 ; 1-Fluoro-2-methoxy
-1-Cyclopentanecarboxylic acid tert-butyl ether
Production of cis ster compound (Compound No. 20a); 1-fluoro-2-hydroxy-1 synthesized in Example 1
The cis-form of cyclopentanecarboxylic acid methyl ester (Compound No. 2a) was methylated by the same method as in Example 10 and further hydrolyzed by the same method as in Example 11 to give 1-fluoro-2-methoxy-1-. A cis form of cyclopentanecarboxylic acid (Compound No. 12a) was obtained. 5 ml of 0.4 g (2.7 mmol) of this carboxylic acid and 0.20 g (2.7 mmol) of tert-butyl alcohol
Was dissolved in ether, 0.56 g (2.7 mmol) of dicyclohexylcarbodiimide and 15 mg of 4,4-dimethylaminopyridine were added, and the mixture was stirred at room temperature for 2 hours. The reaction solution is filtered, ether is added to the filtrate, a diluted hydrochloric acid aqueous solution,
The extract was washed successively with saturated saline solution, saturated aqueous sodium hydrogen carbonate solution and saturated saline solution. The ether layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and 0.31 g of the desired cis form of 2-methoxy-1-fluoro-1-cyclopentanecarboxylic acid tert-butyl ester (Compound No. 20a) was obtained.
(Yield: 56%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.47
-2.80 (6H, m), 1.53 (9H, s), 3.3
7 (3H, s), 3.57-4.37 (1H, m) pp
m.

Example 13 ; 1-Fluoro-2-methoxy
-1-Cyclopentanecarboxylic acid tert-butyl ether
Preparation of cis form of amide (Compound No. 29a); 1-fluoro-2-methoxy-described in Example 12
The cis form of 1-cyclopentanecarboxylic acid (Compound No. 1
2a) 0.4 g (2.7 mmol) and triethylamine 0.27 g (2.7 mmol) were added to tetrahydrofuran 10
It was dissolved in ml and cooled to 0 ° C. 0.29 g (2.7 mmol) of ethyl chlorocarbonate was added dropwise, and the mixture was stirred at 0 ° C. for 1 hour, then 0.24 g (3.
2 mmol) was added, and the mixture was further stirred at room temperature for 1 hour. The reaction mixture was poured into water, extracted with ether, and washed with saturated saline. The ether layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain 0.3 g of the desired cis-form (compound No. 29a) of 1-fluoro-2-methoxy-1-cyclopentanecarboxylic acid tert-butylamide. :
55%).

¹ H-NMR (δ, CDCl ₃ ): 1.43
-2.57 (6H, m), 1.39 (9H, s), 3.3
7 (3H, s), 3.83-4.28 (1H, m) pp
m.

Example 14 ; 1-Fluoro-2-methoxy
-1-Cyclopentanecarboxylic acid tert-butyl ester
Preparation of trans form of allyl ester (Compound No. 38b)
Construction; 1-fluoro-2-methoxy-1 synthesized in Example 11
0.4 g (2.7 mmol) of trans form of cyclopentanecarboxylic acid (Compound No. 12b) and 0.24 g (2.7 mmol) of tert-butyl thiol were dissolved in 5 ml of ether, and 0.56 g (2.7 mmol of dicyclohexylcarbodiimide) was dissolved. ) And 15 mg of 4,4-dimethylaminopyridine were added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was filtered, ether was added to the filtrate, and the mixture was washed successively with diluted hydrochloric acid aqueous solution, saturated saline solution, saturated sodium hydrogen carbonate aqueous solution, and saturated saline solution. The ether layer is dried over anhydrous magnesium sulfate, the solvent is distilled off, and the target 2-methoxy-1-fluoro-1-cyclopentanecarboxylic acid tert-butyl thiol ester trans form (Compound No. 38b) is obtained.
0.48 g (yield: 83%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.30
-2.60 (6H, m), 1.48 (9H, s), 3.3
3 (3H, s), 3.42-4.37 (1H, m) pp
m.

Example 15 ; 2-benzyloxy-1-ph
Luoro-1-cyclohexanecarboxylic acid ethyl ester
Of the trans form (compound No. 107b) of 1-fluoro-2-hydroxy-1 synthesized in Example 3
0.5 g (3 mmol) of trans isomer of cyclohexanecarboxylic acid ethyl ester (Compound No. 73b) was dissolved in 5 ml of dry tetrahydrofuran, cooled to 0 ° C., and 0.12 g of sodium hydride (60% suspension in mineral oil).
(3 mmol) was added. When the generation of hydrogen gas stopped, tetra-n-butylammonium iodide 11 mg
(3 mmol) and benzyl bromide 0.52 g (3 m
mol) were added sequentially. After stirring at room temperature for 5 hours, the reaction solution was poured into a dilute hydrochloric acid aqueous solution and extracted with ethyl acetate.
The ethyl acetate layer was washed successively with saturated brine, saturated aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated to give the desired 2-benzyloxy-1-fluoro-1-cyclohexanecarboxylic acid. Trans form of acid ethyl ester (Compound No. 107b)
3 g (yield: 36%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.25
(3H, t, J = 7Hz) 1.23-2.30 (8H,
m), 3.23-4.00 (1H, m), 4.18 (2
H, q, J = 7 Hz), 4.43 (1H, d, J = 12)
Hz), 4.60 (1H, d, J = 12Hz), 7.23
(5H, s) ppm.

Example 16 ; 2-benzyloxy-1-ph
Luoro-1-cyclohexanecarboxylic acid cis form (compound
No. 105a); 1-fluoro-2-hydroxy-1 synthesized in Example 3
The cis form of cis-hexanecarboxylic acid ethyl ester (Compound No. 73a) was benzylated in the same manner as in Example 15 to give the cis-form of 2-benzyloxy-1-fluoro-1-cyclohexanecarboxylic acid ethyl ester (Compound No. 107a) was obtained. This was hydrolyzed in the same manner as in Example 11 to give the desired 2-benzyloxy-1-
A cis form of fluoro-1-cyclohexanecarboxylic acid (Compound No. 105a) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 0.80
-2.85 (8H, m), 3.28-4.12 (1H,
m), 4.60 (1H, s), 7.27 (5H, s) pp
m.

Example 17 : 1-chloro-2-hydroxy
Ethyl-1-cyclohexanecarboxylate (Compound No. 1
64) Production: First, ethyl 1-chloro-2-oxocyclohexanecarboxylate was produced from ethyl 2-oxocyclocarboxylate with reference to the method described in Organic Synthesis, Vol. 4, p. 162. 17 g (0.1 mol) of ethyl 2-oxocyclocarboxylate was added to 50 m of carbon tetrachloride.
1 l, and 14.8 g (0.11 mol) of sulfuryl chloride dissolved in 15 ml of carbon tetrachloride.
Was added dropwise while cooling with ice. After stirring at room temperature for 2 hours, the reaction solution was poured into 100 ml of ice water, washed with 50 ml of carbon tetrachloride three times, washed with 75 ml of saturated sodium bicarbonate water twice, and washed with 75 ml of saturated saline water once, and dried with anhydrous sulfuric acid. It was dried with magnesium. The solvent was distilled off to obtain 18 g of ethyl 1-chloro-2-oxocyclohexanecarboxylate (yield, 88%). Dimethyl sulfidoborane 1.22 ml (2 mmo
l) is dissolved in 40 ml of tetrahydrofuran and -5 ° C.
At 0 ° C., 2.5 g (12 mmol) of ethyl 1-chloro-2-oxocyclohexanecarboxylate was added dropwise. 0
After stirring at ℃ for 1 hour, the tetrahydrofuran was distilled off under reduced pressure,
The reaction solution was poured into 50 ml of ice water. It was extracted 3 times with 50 ml of ethyl acetate, the obtained organic layer was washed once with 75 ml of saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 2.2 g of a stereoisomer mixture of ethyl 1-chloro-2-hydroxycyclohexanecarboxylate.

¹ H-NMR (δ, CDCl ₃ ); 0.84
-3.02 (8H, m), 1.3 (3H, t, J = 7H
z), 3.25-4.48 (1H, m), 4.25 (2
H, q, J = 7 Hz) ppm.

Example 18 1-Fluoro-2- (4,6)
-Dimethoxypyrimidinyl-2-oxy) -1-cyclo
Trans form of methyl pentanecarboxylate (Compound No. 1
Preparation of 003b) 1.55 g (9.6 mmol) of trans-form of methyl 1-fluoro-2-hydroxycyclopentanecarboxylate prepared according to the method of Example 1 was dissolved in 40 ml of dimethylformamide and added to the solution. Sodium hydride (60% suspension in mineral oil) 0.38 g (9.6 mmol) and 4,6-dimethoxy-2-methylsulfonylpyrimidine 2.0 g (9.6 mmol) were added, and the mixture was stirred at room temperature for 5 hours. .. The reaction solution was poured into 150 ml of water, extracted three times with 50 ml of ethyl acetate, the obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 2.6 g of a crude product. This is purified by silica gel chromatography (developing solvent: hexane / ethyl acetate = 10/1) to obtain the desired 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid. Substance presumed to be the trans form of the cis form of methyl acid (the 2-position substituent has the trans configuration when the 1-position methoxycarbonyl group is used as a reference) (Compound No. 1003b)
0.6 g (yield: 20.9%) was obtained.

¹ H-NMR (δ, CDCl ₃ ); 1.53
-2.77 (m, 6H), 3.71 (s, 3H), 3.8
7 (s, 6H), 5.3-5.76 (m, 1H), 5.6
3 (s, 1H) ppm.

Example 19 1-chloro-2- (4,6-
Dimethoxypyrimidinyl-2-oxy) -1-cyclohe
Trans form of ethyl xanthate (Compound No. 12
Preparation of 03b) Ethyl 1-chloro-2-hydroxy-1-cyclohexanecarboxylate 2.1 synthesized according to the method of Example 17
g (10 mmol) was dissolved in 30 ml of dimethylformamide, and sodium hydride (6 in mineral oil) was added to the solution.
0% suspension) 0.4 g (10 mmol) and 4,6-dimethoxy-2-methylsulfonylpyrimidine 2.2 g
(10 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into 150 ml of water, extracted three times with 50 ml of ethyl acetate, the obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off and the crude product 2.
9 g was obtained. This is purified by silica gel chromatography (developing solvent: hexane / ethyl acetate = 12/1) to obtain the desired 1-chloro-2- (4.6-dimethoxypyrimidinyl-2-oxy) -1-cyclohexanecarboxylic acid. 0.33 g (yield: 10%) of a substance (Compound No. 1203b) presumed to be the trans form of ethyl (the 2-position substituent has a trans configuration when the 1-position ethoxycarbonyl group is used as a reference) was obtained.

Example 20 ; 1-Fluoro-2- (4,6)
-Dimethoxypyrimidinyl-2-oxy) -1-cyclo
Trans-form of pentanecarboxylic acid (Compound No. 1002
Preparation of b) 1-Fluoro-2-synthesized according to the method of Example 2
(4,6-dimethoxypyrimidinyl-2-oxy) -1
-Methyl cyclopentanecarboxylate trans form (Compound No. 1003b) 0.6 g (2 mmol) was added to a mixed solution of methanol 5 ml and water 10 ml, potassium hydroxide 0.34 g was added, and the mixture was stirred at 40 ° C for 1 hour. Ethanol After distilling off and adding 30 ml of water to the reaction solution, the mixture was acidified with diluted hydrochloric acid and extracted 3 times with 30 ml of ethyl acetate.
The ethyl acetate layer was dried over anhydrous magnesium sulfate and the solvent was distilled off to obtain the trans form of the desired 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b. ) 0.27
g (yield: 47.2%) was obtained. Melting point 122-124
° C.

Example 21 1-Fluoro-2- (4,6)
-Dimethoxypyrimidinyl-2-oxy) -1-cyclo
Trans-form of pentanecarboxylic acid isopropyl ester
Production of (Compound No. 1006b ) 0.5 g (1.74 mmol) of 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b).
Isopropyl alcohol in 10 ml of the ether solution of
12 g (1.74 mmol) was added, and at room temperature, 0.4 g (1.93 mmol) of dicyclohexylcarbodiimide and 20 mg of 4,4-dimethylaminopyridine were added. Two
After stirring for an hour, the reaction solution was filtered and concentrated to obtain a crude product. This was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 4/1) to obtain the desired 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarvone. Trans form of acid isopropyl ester (Compound No. 1006
b) 0.4 g (yield: 70%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.16
(3H, d, J = 6.2Hz), 1.26 (3H, d, J
= 6.2 Hz), 1.51-2.68 (6 H, m), 3.8
9 (6H, s), 5.03 (1H, sep), 5.66
(1H, s), 5.31-5.95 (1H, m) ppm.

Example 22 ; 1-Fluoro-2- (4,6)
-Dimethoxypyrimidinyl-2-oxy) -1-cyclo
Trans of pentanecarboxylic acid ethanethiol ester
Preparation of Compound (Compound No. 4214b ) 0.5-g (1.74 mmol) of 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b)
0.14 ml of ethanethiol to 10 ml of ether solution
(1.74 mmol) was added, and 0.4 g (1.93 mmol) of dicyclohexylcarbodiimide was added at room temperature to 4,4-
20 mg of dimethylaminopyridine was added. After stirring for 2 hours, the reaction solution was filtered and concentrated to obtain a crude product. Silica gel column chromatography (developing solvent:
Hexane / ethyl acetate = 9/1) to obtain the desired 1-
Fluoro-2- (4,6-dimethoxypyrimidinyl-2
-Oxy) -1-cyclopentanecarboxylic acid ethanethiol trans form (Compound No. 4214b)
0.3 g (yield: 52%) was obtained.

Example 23 ; 1-fluoro-2- (4,6
-Dimethoxypyrimidinyl-2-oxy) -1-cyclo
Hexanecarboxylic acid isopropylamine salt trans form
Preparation of (Compound No. 1119b) 1-Fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclohexanecarboxylic acid (Compound No. 1081b) 0.4 g (1.34 mmol) in ethanol solution 5 ml at room temperature And isopropylamine 0.88
After adding g (1.5 mmol) and stirring for 30 minutes,
After concentration under reduced pressure, 0.48 g (yield: 99%) of the trans form (compound No. 1119b) of 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclohexanecarboxylic acid isopropylamine salt of interest. ) Got.

Example 24 N, N-dimethyl, 1-fur
Oro-2- (4,6-dimethoxypyrimidinyl-2-o
Xy) -1-cyclopentanecarboxamide trans
Preparation of Compound (Compound No. 4010b) A solution of 0.4 g (1.4 mmol) of 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b) in tetrahydrofuran. 6 ml was cooled to 0 ° C., and 0.19 ml (1.4 mmol) of triethylamine and 0.13 ml (1.4 mmol) of ethyl chlorocarbonate were added. After stirring for 1 hour at 0 ° C., a 50% dimethylamine aqueous solution of 0.1
15 g was added, and the mixture was further stirred for 2 hours. Water was added to the reaction solution, extraction was performed with ether, and the ether layer was washed successively with diluted hydrochloric acid and saturated brine. The ether layer was dried over anhydrous sodium sulfate, the solvent was distilled off, and the crude product was subjected to silica gel column chromatography (developing solvent: hexane / ethyl acetate =
1/9) and the desired N, N-dimethyl, 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxamide trans form (compound No. 4010b). 29 g (yield: 68
%) Was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.67
-2.67 (6H, m), 2.73-3.20 (6H,
m), 3.87 (6H, s), 5.62 (1H, s),
5.47-6.05 (1H, m) ppm.

Example 25 : Methyl, O-methoxycarbo
Nylmethyl-1-fluoro-2- (4,6-dimethoxy
Pyrimidinyl-2-oxy) -1-cyclopentanehydr
Roximate (Compound No. 4096b) 1-Fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b) 0.8 g (2.8 mmol) in 10 ml of a tetrahydrofuran solution containing triethylamine. 0.8m
l, cooled to 0 ° C., and ethyl chloroformate 0.26
ml (2.8 mmol) was added dropwise. After stirring for 1 hour, 0.36 g of methyl aminooxyacetate (3.4 mmo
1) was added and the mixture was stirred for another 2 hours. The reaction solution was poured into saturated saline and extracted with ether. The ether layer was washed successively with diluted hydrochloric acid aqueous solution and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain a crude product. Silica gel column chromatography (developing solvent: hexane /
Purification with ethyl acetate = 4/1) and the desired N-methoxycarbonylmethoxy, 1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxamide (Compound No. 4048b). 66 g
(Yield: 63%) was obtained.

¹ H-NMR (δ, CDCl ₃ ): 1.70
-2.77 (6H, m), 3.76 (3H, s), 3.9
4 (6H, s), 4.41 (2H, s), 5.70 (1
H, s), 5.33-6.00 (1H, m), 9.43-
9.73 (1 H, bs) ppm. Melting point: 68-70.2
° C.

Next, this amide (Compound No. 4048
b) 0.66 g (1.7 mmol) of ether solution 10 m
An ether solution containing 1.5 equivalents of diazomethane was added to 1 under ice cooling, and the mixture was stirred for 1 hour. After acetic acid was added to the reaction solution to decompose excess diazomethane, the solvent was distilled off, and the obtained crude product was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 9/1). Target methyl, O-methoxycarbonylmethyl-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanehydroxymate (Compound No. 4096b) 0.67 g (yield: 97%) Got

¹ H-NMR (δ, CDCl ₃ ): 1.56
-2.59 (6H, m), 3.69 (3H, s), 3.9
2 (6H, s), 4.10 (3H, s), 4.44 (2
H, s), 5.66 (1H, s), 5.39-5.92
(1H, m) ppm. Melting point 72.5-74 [deg.] C.

Example 26 ; (+) and (-)-1-ph
Luoro-2- (4,6-dimethoxypyrimidinyl-2-
Oxy) -1-cyclopentanecarboxylic acid trans form
(Compound Nos. 1002b1, 1002b2) and it
Methyl ester (compound No. 1003b1, 100
Preparation of 3b2) 1-Fluoro-2- (4,6 ) obtained as described above
-Dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b) 6.15
g (21.5 mmol) of isopropyl alcohol 40
It was dissolved in ml, 7 g (21.5 mmol) of quinine was added, and the produced salt was dissolved under heating under reflux. The mixture was allowed to stand overnight at room temperature, and the reaction solution was filtered to obtain 10.65 g of a salt (referred to as No. 1 crystal). The salt was recrystallized twice from 40 ml of isopropyl alcohol to give pure (+)-1.
-Fluoro-2- (4,6-dimethoxypyrimidinyl-
4.4 g of the quinine salt of the trans form of 2-oxy) -1-cyclopentanecarboxylic acid (Compound No. 1002b1) was obtained. 3.54 g of this salt was dissolved in 40 ml of 1N hydrochloric acid, 50 ml of ether was added, and the mixture was stirred for 1 hour. The ether layer was separated, dried over anhydrous magnesium sulfate, and the solvent was distilled off to give the desired (+)-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid. Trans form (Compound No. 1002b1) 1.
49 g (24.2%) were produced.

[Α] _D ³⁰ = + 36.62 ° (c = 0.07)
1, i-PrOH) Next, the mother liquor obtained by recrystallizing the above No. 1 crystal was concentrated and precipitated (-)-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclo. 3.53 g of the quinine salt of the trans form of pentanecarboxylic acid (Compound No. 1002b2) was decomposed by the same method as described above to obtain the desired (-)-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2- Oxy) -1-cyclopentanecarboxylic acid trans form (Compound No. 1002b2) 1.09 g
(17.7%) was produced.

[Α] _D ³⁰ = −38.55 ° (c = 0.08)
3, i-PrOH) 1.49 g of the (+)-isomer optically active carboxylic acid (Compound No. 1002b1) obtained as described above was converted into ether 2
It was dissolved in 0 ml, and methyl ether was added by adding a necessary amount of an ether solution of diazomethane under ice cooling. Excess diazomethane was decomposed with acetic acid and the solvent was distilled off to obtain the desired (+)-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-
Oxy) -1-cyclopentanecarboxylic acid methyl ester trans form (Compound No. 1003b1) 1.5 g
(95.6%) was obtained.

Analysis with an optical isomer separation column (CHIRALCEL OD manufactured by Daicel Chemical Industries, Ltd.) (solvent system:
Hexane / isopropyl alcohol = 9/1, flow rate: 2
(ml / min, detection wavelength: 254 nm), the result was that this ester had an excess of 99% of the antipode.

Next, (-)-1-fluoro-2- (4,6)
-Dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid trans form (Compound No. 1002
b2) 1.09 g was methylated in the same manner as in the (+) form to give (−)-1-fluoro-2- (4,6-dimethoxypyrimidinyl-2-oxy) -1-cyclopentanecarboxylic acid methyl ester. Trans form (Compound No. 100
3b2) 1.11 g (96.4%) was obtained.

As a result of analysis under the same conditions as for the (+) form, this ester was found to be 86.8% in excess of enantiomer.

The compound represented by the above general formula (I) of the present invention has activity as a herbicide. In that case,
Prepared by mixing with a carrier or diluent, an additive, an auxiliary agent and the like by a method known per se, into a formulation form usually used as an agricultural chemical, for example, powder, granule, wettable powder, emulsion, water solvent, flowable agent, etc. Then used. Further, it can be used in combination or in combination with other pesticides such as fungicides, insecticides, acaricides, other herbicides, plant growth regulators, fertilizers and soil conditioners. In particular, by using it in combination with other herbicides, not only the amount of the drug used can be reduced and labor saving can be achieved, but also a broader herbicidal spectrum due to the synergistic action of both drugs and a higher synergistic effect can be expected.

Specific examples of other herbicides which can be used by mixing with the compound of the present invention represented by the above general formula (I) include, for example, carbamate herbicide : methyl 3,4-dichlorophenylcarbamate (general). Name: Swep), isopropyl 3-chlorophenyl carbamate (generic name: Chlorpropham), S- (p-chlorobenzyl) N, N-diethylthiocarbamate (generic name: Benthiocarb), S- Ethyl-N, N-hexamethylene thiocarbamate (generic name: molinate,
Molinate), S- (1-methyl-1-phenylethyl)
Piperidine-1-carbothioate (generic name: dimepiperate, Dimepiperate), S-benzyl-N-ethyl-
N- (1,2-dimethylpropyl) thiol carbamate (generic name: esprocarb, Esprocarb), [(methoxycarbonyl) amino] phenyl (3-methylphenyl) carbamate (generic name: fuemmediphum, Phenme
dipham), ethyl 3-phenylcarbamoyloxyphenylcarbamate (generic name: Desmedipam)
ham), O- (3-tert-butylphenyl) -N-
(6-Methoxy-2-pyridyl) -N-methyl-thiocarbamate (generic name: pyributycarb, Pyributycarb)
Urea herbicide : 1- (α, α-dimethylbenzyl)-
3- (4-methylphenyl) urea (generic name: Dymron), 3- (3,4-dichlorophenyl) -1,
1-dimethylurea (generic name: Diuron),
1,1-dimethyl-3- (α, α, α-trifluoro-m
-Tolyl) urea (generic name: fluometulon, Fluometu
ron), 3- [4- (4-chlorophenoxy) phenyl] -1,1-dimethylurea (generic name: chloroxuron, Chloroxuron), 3- (3,4-dichlorophenyl)
-1-Methoxy-1-methylurea (generic name: Linuron, Linouron), 3- (4-chlorophenyl) -1-methoxy-1-methylurea (generic name: monolinuron,
Monolinurone), 3- (4-bromo-3-chlorophenyl) -1-methoxy-1-methylurea (generic name: Chlorbromron), 1- (α, α-dimethylbenzyl) -3- (2-chloro) Benzyl) urea (code number: JC-940) and the like; haloacetamide herbicide : 2-chloro-2 ′, 6′-
Diethyl-N-methoxymethylacetanilide (generic name: Alachlor), N-butoxymethyl-
2-chloro-2 ', 6'-diethylacetanilide (generic name: butachlor, Butachlor), 2-chloro-2',
6'-diethyl-N- (2-propoxyethyl) acetanilide (generic name: pretilachlor, Pretilachlo
r), 2-chloro-N-isopropylacetanilide (generic name: propachlor), amide herbicide : 3 ', 4'-dichloropropionanilide (generic name: propanil, Propanil), 2-bromo-
N- (1,1-dimethylbenzyl) -3,3-dimethylbutanamide (generic name: bromobutide),
2-benzothiazol-2-yloxy-N-methylacetanilide (generic name: mefenase, Mefenase
t), N, N-dimethyldiphenylacetamide (generic name: diphenamide, Diphenamid), N- [2 '-(3'
Methoxy) -thienylmethyl] -N-chloroaceto-
2,6-Dimethylanilide (code number: NSK-85
0), 2 ', 6-diethyl-N-[(2-cis-butenooxy) methyl] -2-chloroacetanilide (code number: KH-218) and the like; dinitrophenyl herbicide : 4,6-dinitro-o- Cresol (generic name: DNOC), 2-tert-butyl-
4,6-dinitrophenol (generic name: dinotab, Dinot
erb), 2-sec-butyl-4,6-dinitrophenol (generic name: dinoceb, Dinoseb), N, N-diethyl-
2,6-dinitro-4-trifluoromethyl-m-phenylenediamine (generic name: dinitramine, Dinitramin
e), α, α, α-trifluoro-2,6-dinitro-N,
N-dipropyl-p-toluidine (generic name: trifluralin, Trifluralin), 4-methylsulfonyl-2,6-
Dinitro-N, N-dipropylaniline (generic name: Nitralin), N- (1-ethylpropyl)-
2,6-dinitro-3,4-xylidine (generic name: pendimethalin, Pendimethalin) and the like; phenoxy herbicide : 2,4-dichlorophenoxyacetic acid (generic name: 2,4-D), 2, 4,5-Trichlorophenoxyacetic acid (generic name: 2,4,5-T), 4-chloro-o-
Trilyloxyacetic acid (generic name: MCPA), 4- (4-chloro-o-tolyloxy) butyric acid (generic name: MCPB), 2,4-
Dichlorophenoxybutyric acid (generic name: 2,4-DB), 2
-(4-Chloro-o-tolyloxy) propionic acid (generic name: mecopropup, Mecoprop), 2- (2,4-dichlorophenoxy) propionic acid (generic name: diclopropup, Dichlorprop), (RS) -2- [4- (2,4-dichlorophenoxy) phenoxy] propionic acid (generic name:
Diclofop) and its esters, (RS)
-2- [4- (5-trifluoromethyl-2-pyridyloxy) phenoxy) propionic acid (generic name: Fluazifop) and its esters, 2- (2,4-
Dichloro-3-methylphenoxy) propionanilide (generic name: Cromeprop, Cromeprop), S-ethyl-4-chloro-2-methylphenoxythioacetate (generic name: Phenothiol), 2- (2-
Naphthoxy) propionanilide (generic name: Naproanilide, Naproanilide), etc .; carboxylic acid herbicide : 2,2-dichloropropionic acid (generic name: dalapone, Dalapone), trichloroacetic acid (generic name: TCA), 2,3,6 -Trichlorobenzoic acid (generic name: 2,3,6-TBA), 3,6-dichloro-o-anisuccinic acid (generic name: Dicamba), 3-amino-2,5-dichlorobenzoic acid ( General name: Chloramben, etc .; Organophosphorus herbicide : O-ethyl O- (2-nitro-5)
-Methylphenyl) -N-sec-butylphosphloamiothioate (generic name: Butamifus, Butamif
o), O, O-diisopropyl-S- (2-benzenesulphonylaminoethyl) phosphorodithioate (generic name: SAP), S- (2-methylpiperidin-1-yl) carbonylmethyl O, O- Dipropylfuoshuolodithioate (generic name: Piperophos)
Etc .; benzonitrile herbicide : 2,6-dichlorobenzonitrile (generic name: diclobenil, Dichlobenil), 3,5-
Dibromo-4-hydroxylbenzonitrile (generic name:
Bromoxynil), 4-hydroxy-3,
5-diiodobenzonitrile (generic name: ioxynil,
Ioxynil) etc .; diphenyl ether herbicides : 2,4-dichlorophenyl 4-nitrophenyl ether (generic name: nitrophen, Nitrofen), 2,4,6-trichlorophenyl 4 '
-Nitrophenyl ether (generic name: Chlornitrofen), 2,4-dichlorophenyl 3-
Methoxy-4-nitrophenyl ether (generic name: Chlomethoxynil), methyl 5- (2,
4-dichlorophenoxy) -2-nitrobenzoate (generic name: Bifenox, Bifenox), 4-nitrophenyl α, α, α-trifluoro-2-nitro-p-tolyl ether (generic name: fluorodiphene, Fluorodife
n), 2-chloro-4-trifluoromethylphenyl
3-ethoxy-4-nitrophenyl ether (generic name:
Oxyfluorfen), 5- (2-chloro-α, α, α-trifluoro-p-tolyloxy)-
2-Nitrobenzoic acid (generic name: acifluorfen, Ac
trifluorinated herbicide : 4-amino-3-methyl-6-phenyl-1,2,4-triazin-5 (4H) -one (generic name: Metamitron), 4-amino-6-
tert-Butyl-3-methylthio-1,2,4-triazin-5 (4H) -one (generic name: metribuzin, Metr
ibuzin), 2-chloro-4,6-bis (ethylamino)
-1,3,5-triazine (generic name: simazine, Simazin
e), 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine (generic name: atrazine, Atrazine), 2,4-bis (ethylamino) -6-
Methylthio-1,3,5-triazine (generic name: cimetrin, Simetoryne), 2,4-bis (isopropylamino) -6-methylthio-1,3,5-triazine (generic name: promethrin, Prometryne), 2- Methylthio-4
-Ethylamino-6- (1,2-dimethylpropylamino) -1,3,5-triazine (generic name: dimetamethrin, Dimetametryne) and the like; sulfonylurea herbicide : 2-chloro-N-[(4-
Methoxy-6-methyl-1,3,5-triazin-2-yl) aminocarbonyl] benzenesulfuronamide (generic name: Chlorsulfuron), methyl
2-{[((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) aminosulfonyl] methyl} benzoate (generic name: bensulfuron-methyl, Bensulfu
ron methyl), ethyl 2-[((4-chloro-6-methoxypyrimidin-2-yl) aminocarbonyl) aminosulfonyl] benzoate (generic name: chlorimuron ethyl, Chlorimuron ethyl), ethyl 5-[((4 , 6
-Dimethoxypyrimidin-2-yl) aminocarbonyl) aminosulfonyl] -1-methyl-1H-pyrazole-4-carboxylate (generic name: pyrazosulfuron ethyl), 2- (2-methoxyethoxy) -N -[(4,6-dimethoxy-1,3,5-
Triazin-2-yl) aminocarbonyl] benzenesulfonamide (generic name: cynosulfuron, Synosulfur
on), 2-chloro-N-[(4,6-dimethoxypyrimidin-2-yl) aminocarbonyl] imidazo [1,2
-A] pyridine-3-sulfonamide (code number:
TH-913) and the like; diazine herbicide : 4- (2,4-dichlorobenzoyl) -1,3-dimethylpyrazol-5-yl-p-toluenesulfonate (generic name: pyrazolate, Pyrazola
te) 1,3-dimethyl-4- (2,4-dichlorobenzoyl) -5-phenacyloxypyrazole (generic name: pyrazoxoxyphen, Pyrazoxyfen), 1,3-dimethyl-4
-(2,4-Dichloro-3-methylbenzoyl) -5-
(4-methylphenacyloxy) pyrazole (generic name:
Benzofenap) and other herbicides : 3,6-dichloropyridine-2-carboxylic acid (generic name: clopyralid, Clopyralid), 4-amino-3,5,6-trichloropyridine-2-carboxylic acid (general) Name: Picloram, Picloram), 5-amino-4-
Chloro-2-phenylpyridazin-3 (2H) -one (generic name: chloridazon, Chloridazon), 3-cyclohexyl-1,5,6,7-tetrahydrocyclopentapyrimidin-2,4 (3H) -dione ( Generic name: Lenacil), 5-bromo-3-sec-butyl-6
-Methyluracil (generic name: Bromacil),
3-tert-butyl-5-chloro-6-methyluracil (generic name: terbacil), 3-isopropyl-1H-2,1,3-benzothiadiazine-4 (3H)
-On-2,2-dioxide (generic name: bentazone, Ben
tazone), N-1-naphthylphthalamic acid (generic name: Naptalam, Naptalam), S, S-dimethyl-2- (difluoromethyl) -4- (2-methylpropyl) -6-
(Trifluoromethyl) -3,5-pyrimidine carbothioate (code number: Mon-72), 2,3-dihydro-3,3-dimethyl-5-benzofuranylethanesulphonate (generic name: benfresate, Benfuresat
e), 5-tert-butyl-3- (2,4-dichloro-
5-isopropoxyphenyl) -1,3,4-oxadiazol-2 (3H) -one (generic name: oxadiazone,
Oxadiazon), exo-1-methyl-4- (1-methylethyl) -2-[(2-methylphenyl) methoxy]-
7-oxabicyclo [2,2,1] heptane (code number: SKH-301) and the like can be mentioned.

As the carrier or diluent used for formulating the compound of the present invention alone or in combination with other herbicides, solid or liquid carriers generally used in agriculture are used. Examples of solid carriers include clays represented by kaolinite group, montmorillonite group, illite group or apatargite group, talc and diatomaceous earth, magnesium coal, phosphate rock, zeolite, zeolide, silicic acid anhydride, synthetic calcium silicate, etc. Inorganic substances; Soybean flour, tobacco flour, walnut flour, wheat flour, wood flour, starch, crystalline cellulose and other plant organic substances; coumarone resin, petroleum resin, alkyd resin, polyvinyl chloride, polyalkylene glycol, ketone resin, ester Gum,
Examples thereof include synthetic or natural polymer compounds such as cobal gum and dammal gum; waxes such as carnauba wax and beeswax, and urea. Suitable liquid carriers include, for example, paraffinic or naphthenic hydrocarbons such as kerosene, mineral oil, spindle oil, or white oil; aromatic hydrocarbons such as toluene, xylene, ethylbenzene, cumene, or methylnaphthalene; dioxane, or Ethers such as tetrahydrofuran; ketones such as methyl ethyl ketone, diisobutyl ketone, cyclohexanone, acetophenone, or isophorone; esters such as ethyl acetate, amyl acetate, ethylene glycol acetate, diethylene glycol acetate, dibutyl maleate, or diethyl succinate; methanol , N-hexanol, ethylene glycol, diethylene glycol, cyclohexanol, alcohols such as benzyl alcohol, ethylene glycol Le ethyl ether, ethylene glycol phenylalanine ether, ether alcohols such as diethylene glycol ethyl ether or diethylene glycol butyl ether; dimethylformamide or polar solvents or water such as dimethyl sulfoxide, and the like.

In addition, emulsification, dispersion of the compound of the present invention,
Surfactants and other auxiliary agents can be used for the purposes of wetting, spreading, binding, controlling disintegration, stabilizing active ingredients, improving fluidity, and preventing rust. Examples of surfactants used may be nonionic, anionic, cationic and zwitterionic, but are usually nonionic and / or anionic. A compound is used.

Suitable nonionic surfactants include, for example, lauryl alcohol, stearyl alcohol,
Or a compound obtained by polymerizing addition of ethylene oxide to a higher alcohol such as oleyl alcohol; a compound obtained by polymerizing addition of ethylene oxide to an alkylphenol such as isooctylphenol or nonylphenol; polymerized ethylene oxide to an alkylnaphthol such as butylnaphthol or octylnaphthol Added compound;
Compounds obtained by polymerizing addition of ethylene oxide to palmitic acid or higher fatty acids such as stearic acid and oleic acid;
Examples thereof include higher fatty acid esters of polyhydric alcohols such as sorbitan and compounds obtained by polymerizing addition of ethylene oxide thereto; compounds obtained by block polymerization addition of ethylene oxide and propylene oxide.

Suitable anionic surfactants include, for example, sodium lauryl sulfate or alkyl sulfate salts such as oleyl alcohol sulfate amine salt.
Alkyl sulfonates such as sodium sulfosuccinate dioctyl ester or sodium 2-ethylhexene sulfonate; aryl sulfones such as sodium isopropylnaphthalene sulfonate, sodium methylenebisnaphthalene sulfonate, sodium lignin sulfonate, or sodium dodecylbenzene sulfonate Examples thereof include acid salts.

Further, the herbicides of the present invention include polymers such as casein, gelatin, albumin, glue, sodium alginate, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose and polyvinyl alcohol for the purpose of improving the properties of the preparation and enhancing the herbicidal effect. Compounds and other auxiliary agents can also be used in combination.

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 content of the compound (active ingredient) of the present invention in the various dosage forms thus obtained varies depending on the dosage form, but usually 0.1 to 99% by weight is suitable, and Most preferred is 1 to 80% by weight.

In the case of powders, for example, the active ingredient compound is usually contained in an amount of 1 to 25% by weight, and the balance is a solid carrier.

In the case of a wettable powder, for example, the active ingredient compound is usually contained in an amount of 25 to 90% by weight, and the balance is a solid carrier and a dispersion wetting agent, and if necessary, a protective colloid agent, a defoaming agent and the like are added. Be done.

In the case of granules, for example, the active ingredient compound is usually contained in an amount of 1 to 35% by weight, and the balance mainly comprises solid carriers and surfactants. The active ingredient compound is uniformly mixed with the solid carrier, or is uniformly fixed or adsorbed on the surface of the solid carrier, and the particle diameter is about 0.2 to 1.5 mm.

In the case of an emulsion, for example, the active ingredient compound is usually contained in an amount of 5 to 60% by weight, and about 5 to 2% of this is contained.
It contains 0% by weight of an emulsifier, the balance being a liquid carrier, optionally with a rust inhibitor.

In the case of a flowable agent, for example, the active ingredient compound is usually contained in an amount of 5 to 50% by weight, the dispersion wetting agent is contained in an amount of 3 to 10% by weight, and the balance is water. A protective colloid agent, an antiseptic agent, an antifoaming agent and the like are added.

The halogenated cycloalkanecarboxylic acid derivative of the present invention can be applied as it is to the compound of the general formula (I) or in any preparation form as described above.

The herbicide of the present invention can be applied to the control or control of various weeds that grow in paddy fields and upland fields from the pre-emergence stage to the growing season. The application rate is 0.0001 to 1 per ha as the amount of the compound represented by the general formula (I) (the amount of active ingredient).
It is about 5 kg, preferably about 0.001 to 0.5 kg, and can be appropriately selected and changed depending on the kind of weed, the growth stage, the place of application, the time of application, the weather and the like.

Next, several embodiments of formulation examples using the compound of the present invention will be shown. "Parts" in the following formulation examples are based on weight.

Formulation Example 1 (Granule) Compound No. 1002b 5 parts Bentonite 40 parts Talc 52 parts Sodium lignin sulfonate 2 parts Polyoxyethylene alkylaryl ether 1 part After thoroughly mixing the above, knead by adding an appropriate amount of water. Then, it was granulated using a granulator to obtain 100 parts of granules.

Formulation Example 2 (Wettable Powder) Compound No. 1002b 20 parts Diatomaceous earth 60 parts White carbon 15 parts Sodium lignin sulfonate 3 parts Sodium dialkylnaphthalene sulfonate 2 parts The above ingredients are mixed and uniformly pulverized with a jet mill. 100 parts of wettable powder was obtained.

Formulation Example 3 (Emulsion) Compound No. 1002b 30 parts Xylene 55 parts Cyclohexanone 10 parts Calcium dodecylbenzenesulfonate 3 parts Polyoxyethylene alkylaryl ether 2 parts The above components were uniformly mixed and dissolved to obtain 100 parts of an emulsion.

Drugs using the compound of the present invention were each prepared according to the above-mentioned preparation examples.

[0177]

The effect of the present invention is represented by the above general formula (I),
The halogenated cycloalkanecarboxylic acid derivative is a novel compound not described in the literature. The general formula (I) of the present invention
The compound represented by is a halogenated cycloalkanecarboxylic acid moiety having a relatively simple structure and a pyrimidine ring or triazine ring moiety having a specific substituent bonded to the 4- and 6-positions thereof via an oxygen atom. It is considered that the excellent herbicidal action is exhibited due to the structural feature.

The compound and the herbicide of the present invention can control various weeds that grow in agricultural land from pre-emergence to growing season. For example, paddy weeds such as Nobie, Firefly, Mizuhigai, Konagi, Azaena, Mizohabe, Kishigusa, Matsubayai, Urikawa, etc., and Crabgrass, Enocorogusa, Ohishiba, Suzunohie, Suzunotsutsupou, Azaleas japonicus, Acacia serrata, Acacia serrata, Acacia serrata, Acacia, It can control various weeds in the field such as, morning glory, white morning glory, morning glory, southern fir, ragweed, herring roe, rapeseed, Sendangusa, yaemgra, wild mustard, wild sunflower and buckwheat vine. Further, it can be used not only in paddy fields and upland fields but also in orchards, mulberry fields, lawns and non-agricultural fields.

Moreover, the compound of the present invention has selectivity for certain cultivated crops, and particularly excellent selectivity for crops such as cotton, soybean and corn.

Next, the herbicidal effect will be described with reference to test examples.

Test Example 1 (Treatment of field foliage) Square pots (30 × 30 × 12 cm) were filled with field soil, and various crops and various weed seeds shown in Table 12 were sown in fixed amounts, and each plant was treated with 1 It was grown in the greenhouse until the 0.5 to 3 leaf stage. The compound of the present invention shown in Table 12 was prepared as a wettable powder according to Formulation Example 2, and the water dilution thereof was adjusted so that the effective amount of the active ingredient shown in Table 12 would be 500 l / ha. Sprayed evenly on the foliage of the plant. Twenty-one days after the chemical spraying, the herbicidal effect on various weeds and the degree of phytotoxicity on various crops were determined according to the criteria shown in Table 11 below.
The results are shown in Table 12.

Test Example 2 (Soil treatment before field germination) [0183] Square pots (30x30x12 cm) were filled with field soil, and various crops and various weed seeds shown in Table 13 were sown in fixed amounts, and then 1 cm. Covered the soil. The compound of the present invention shown in Table 13 was prepared into a wettable powder according to Formulation Example 2, and the diluted solution was adjusted so that the amount of active ingredient shown in Table 13 was 5
It was evenly sprayed on the soil surface at a spraying rate of 00 l / ha. Twenty-one days after the application of the chemicals, the herbicidal effect on various weeds and the degree of phytotoxicity to various crops were determined according to the criteria of Test Example 1. The results are shown in Table 13.

Test Example 3 (Non-selective foliar treatment test) Square pots (30 x 30 x 12 cm) were filled with upland soil and various weed seeds shown in Table 15 were sown in fixed amounts.
Each plant was grown in the greenhouse until the 1.5-3 leaf stage. The compound of the present invention shown in Table 15 was prepared into a wettable powder according to Formulation Example 2, and the water dilution thereof was spread at a spraying amount of 500 l / ha so that the amount of the active ingredient shown in Table 15 was obtained. Surfactant WK (manufactured by Maruwa Biochemical Co., Ltd.) was added to 0.25% and sprayed evenly on the foliage of each plant. Twenty-one days after the application of the chemicals, the herbicidal effect on various weeds was judged according to the criteria shown in Table 14 below. The results are shown in Table 15.

Test Example 4 (Non-selective pre-emergence soil treatment test) Square pots (30 x 30 x 12 cm) were filled with upland soil and various weed seeds shown in Table 16 were sown in fixed amounts, and then 1 cm I covered the soil. The compound of the present invention shown in Table 16 was prepared as a wettable powder according to Preparation Example 2, and the diluted solution was adjusted to 500 l / ha so that the amount of the active ingredient shown in Table 16 was obtained.
Was evenly applied to the soil surface. Twenty-one days after the chemical spraying, the herbicidal effect on various weeds was judged according to the criteria of Test Example 3. The results are shown in Table 16.

[0185]

[Table 11]

[0186]

[Table 12]

[0187]

[Table 13]

[0188]

[Table 14]

[0189]

[Table 15]

[0190]

[Table 16]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location A01N 43/82 104 8930-4H C07C 47/37 9049-4H 62/02 8827-4H 62/08 8827 -4H 62/34 8827-4H 69/63 9279-4H 69/75 Z 9279-4H 69/757 B 9279-4H Z 9279-4H C 9279-4H 69/76 Z 9279-4H 235/40 7106-4H 251 / 42 9160-4H 251/56 9160-4H 251/58 9160-4H 251/60 9160-4H 251/66 9160-4H 309/65 9160-4H 309/67 9160-4H C07D 239/34 8615-4C 239 / 52 8615-4C 239/56 8615-4C 239/60 8615-4C 251/26 251/34 J 251/38 401/12 8829-4C 403/12 8829-4C 405/12 8829-4C 417/12 9051-4C (31) Priority claim number Japanese Patent Application No. 3-50523 (32) Priority date Hei 3 (1991) February 22 (33) Country of priority claim Japan (JP) (31) Priority claim number Japanese Patent Application No. 3-128188 (32) Priority Date No. 3 (1991) May 2 (33) Priority claiming country Japan (JP) (31) Priority claim number Japanese Patent Application No. 3-128208 (32) Priority Date No. 3 (1991) May 2 (33) Japan (JP) claiming priority (72) Inventor Michi Watanabe 8-3-1 Chuo, Ami-cho, Inashiki-gun, Ibaraki Sanritsu Yuka Co., Ltd. Tsukuba Research Institute ( 72) Inventor Takako Takahashi 8-3-1, Chuo, Ami-cho, Inashiki-gun, Ibaraki Sanyo Ryoka Chemical Co., Ltd. Tsukuba Research Institute (72) Takako Aoki 8-3-1-3, Chuo, Ami-cho, Inashiki-gun, Ibaraki Ryoyu Kagaku Co., Ltd., Tsukuba Research Institute (72) Inventor Tokushige Tonoshima 8-3-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki Sanyo Yuka Co., Ltd., Tsukuba Research Institute (72) Inventor, Keiji Endo Inashiki, Ibaraki Prefecture 8-3-1 Chuo, Ami-machi, Gunma Sanryo Yuka Co., Ltd., Tsukuba Research Laboratory (72) Inventor Shuji Mukata 8-3-1, Chuo, Ami-cho, Inashiki-gun, Ibaraki Sanryo Yuka Tsukuba Co., Ltd. (72) Inventor Shinji Kawaguchi 8-3-1 Chuo, Ami-cho, Inashiki-gun, Ibaraki Sanbyo Yuka Co., Ltd. Tsukuba Research Institute (72) Rika Higurashi 8-chome, Ami-cho, Inashiki-gun, Ibaraki 3-1, Sanryo Yuka Co., Ltd. Tsukuba Research Institute

Claims (3)

[Claims] 1. A compound represented by the general formula (I): In the formula, X represents a halogen atom, n represents an integer of 0 to 3, Z ¹ and Z ² are each a nitrogen atom or a group CH.
When Z ¹ is a nitrogen atom, Z ² represents a nitrogen atom or a group CH, and when Z ¹ is a group CH, Z ² represents a nitrogen atom. R ¹ and R ² are each independently hydrogen. An atom, a halogen atom, a mono- or di-lower alkyl-substituted amino, or in each case a lower alkyl, a lower alkoxy or a lower alkylthio optionally substituted by a halogen atom, A represents an oxygen atom or a group = N-B Where B is hydroxy, lower alkylcarbonyloxy or, in each case, lower alkoxy optionally substituted with hydroxycarbonyl or lower alkoxycarbonyl, Y is hydrogen atom, hydroxy, halogen atom in each case , Hydroxy, lower alkyl, lower alkoxy, lower alkylthio, lower alkoxycarbonyl, low Alkylcarbonyl, lower alkoxy optionally substituted with cyano, nitro or azido, lower alkenoxy, lower alkynoxy, lower alkylthio, aryloxy, aralkyloxy, arylthio, aralkylthio, lower cycloalkoxy, lower cycloalkenyloxy, pyridylthio, Furylmethyloxy, furylthio or thienyloxy, or azido, tri-lower alkyl-substituted silyloxy or imidooxy, or [Wherein R ³ and R ⁴ each independently represent a hydrogen atom, lower alkyl, lower alkoxy, aryl or aralkyl, and R ³ and R ⁴ represent a lower cycloalkane ring together with the carbon atom to which they are bonded. R ⁵ and R ⁶ , which may be formed, are each independently a hydrogen atom,
Hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkenoxy, lower alkynoxy, lower alkylcarbonyloxy, cyano, lower alkylsulfonyl optionally substituted with a halogen atom, lower alkyl substituted with lower alkoxycarbonyl, Lower alkyl substituted with hydroxycarbonyl, lower alkoxy substituted with lower alkoxycarbonyl, lower alkoxy substituted with hydroxycarbonyl, halogen atom in each case, hydroxy, lower alkyl, lower alkoxy, lower substituted with halogen atom Alkyl, cyano, nitro, amino, mono or di-lower alkyl substituted aryl, aralkyl, aryloxy, optionally substituted with lower alkoxycarbonyl. Rarukiruokishi, arylcarbonyloxy, pyridyl, ## STR2 ## (Wherein Z ³ represents an oxygen atom, a group CH or a sulfur atom, Z ⁴ represents a nitrogen atom or a group CH, Z ¹ and Z ²
Means the same definition as above, and m is an integer of 0 or 1. (Wherein R ⁷ and R ⁸ are a hydrogen atom, lower alkyl, lower alkoxycarbonyl, lower alkyl substituted with lower alkoxycarbonyl, lower alkyl substituted with hydroxycarbonyl, or in each case a halogen atom, lower alkyl, A halogenated cycloalkanecarboxylic acid derivative represented by lower alkyl, lower alkoxy substituted with a halogen atom, aryl optionally substituted with cyano, amino or nitro, aralkyl, pyridyl or benzothiazolyl) and salts thereof .. 2. A compound represented by the general formula (I): In the formula, X represents a halogen atom, n represents an integer of 0 to 3, Z ¹ and Z ² are each a nitrogen atom or a group CH.
When Z ¹ is a nitrogen atom, Z ² represents a nitrogen atom or a group CH, and when Z ¹ is a group CH, Z ² represents a nitrogen atom. R ¹ and R ² are each independently hydrogen. An atom, a halogen atom, a mono- or di-lower alkyl-substituted amino, or in each case a lower alkyl, a lower alkoxy or a lower alkylthio optionally substituted by a halogen atom, A represents an oxygen atom or a group = N-B Where B is hydroxy, lower alkylcarbonyloxy or, in each case, lower alkoxy optionally substituted with hydroxycarbonyl or lower alkoxycarbonyl, Y is hydrogen atom, hydroxy, halogen atom in each case , Hydroxy, lower alkyl, lower alkoxy, lower alkylthio, lower alkoxycarbonyl, low Alkylcarbonyl, lower alkoxy optionally substituted with cyano, nitro or azido, lower alkenoxy, lower alkynoxy, lower alkylthio, aryloxy, aralkyloxy, arylthio, aralkylthio, lower cycloalkoxy, lower cycloalkenyloxy, pyridylthio, Furylmethyloxy, furylthio or thienyloxy, or azido, tri-lower alkyl-substituted silyloxy or imidooxy, or [Wherein R ³ and R ⁴ each independently represent a hydrogen atom, lower alkyl, lower alkoxy, aryl or aralkyl, and R ³ and R ⁴ represent a lower cycloalkane ring together with the carbon atom to which they are bonded. R ⁵ and R ⁶ , which may be formed, are each independently a hydrogen atom,
Hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkenoxy, lower alkynoxy, lower alkylcarbonyloxy, cyano, lower alkylsulfonyl optionally substituted with a halogen atom, lower alkyl substituted with lower alkoxycarbonyl, Lower alkyl substituted with hydroxycarbonyl, lower alkoxy substituted with lower alkoxycarbonyl, lower alkoxy substituted with hydroxycarbonyl, halogen atom in each case, hydroxy, lower alkyl, lower alkoxy, lower substituted with halogen atom Alkyl, cyano, nitro, amino, mono or di-lower alkyl substituted aryl, aralkyl, aryloxy, optionally substituted with lower alkoxycarbonyl. Rarukiruokishi, arylcarbonyloxy, pyridyl, embedded image (Wherein Z ³ represents an oxygen atom, a group CH or a sulfur atom, Z ⁴ represents a nitrogen atom or a group CH, Z ¹ and Z ²
Means the same definition as above, and m is an integer of 0 or 1. (Wherein R ⁷ and R ⁸ are a hydrogen atom, lower alkyl, lower alkoxycarbonyl, lower alkyl substituted with lower alkoxycarbonyl, lower alkyl substituted with hydroxycarbonyl, or in each case a halogen atom, lower alkyl, A halogenated cycloalkanecarboxylic acid derivative represented by lower alkyl, lower alkoxy substituted with a halogen atom, aryl optionally substituted with cyano, amino or nitro, aralkyl, pyridyl or benzothiazolyl) and salts thereof A herbicide containing as an active ingredient. 3. A compound represented by the general formula (II): In the formula, X, A, n and Y mean the same as defined in the general formula (I), V represents a hydrogen atom, lower alkyl, lower alkylcarbonyl, lower alkylsulfonyl or
In each case, a halogen atom, hydroxy, nitro, cyano, lower alkyl, lower alkoxy, halogen-substituted lower alkyl, halogen-substituted lower alkoxy, amino or aralkyl optionally substituted with mono- or di-lower alkyl-substituted amino, arylcarbonyl or A halogenated cycloalkanol derivative represented by: which represents arylsulfonyl.