JPH08183701A - Substituted piperidinedione derivative and herbicide - Google Patents

Abstract

PURPOSE: To obtain a substituted piperidinedione derivative expressing high herbicidal activities in any one of a soil treatment and a foliage treatment in an upland farming condition. CONSTITUTION: This substituted piperidinedione derivative is expressed by formula I [R<1> is a (substituted)phenyl, a (substituted)pyridyl or a (substituted) aralkyl; R<2> is H, a (substituted)1-4C alkyl, a 2-4C alkenyl, a (substituted)phenyl, a 1-4C alkoxycarbonyl, etc.; X is O, N-R<7> (R<7> is H, a 1-4C alkyl, a 1-4C alkylcarbonyl, a phenylcarbonyl, etc.); R<3> to R<6> are each H, a halogen, a (substituted)1-4C alkyl, a (substituted)phenyl, a 1-4C alkoxycarbonyl, CN, formyl, etc., or R<3> , R<4> and R<5> , R<6> together form a 2-5C alkylene chain, etc.]. E.g. 3-(2- chloro-3-methoxy-4-methylsulfonylbenzoyl)-1-methoxypiperidine-2,4-dione. This compound can be obtained by a two step reaction from a cyclic dione through intermediates of formula IVa and IVb, or by a reaction of a compound of formula II with a compound expressed by the formula R<1> COCN.

Description

Detailed Description of the Invention

[0001]

The present invention has the general formula [I]

[Chemical 4] (In the formula, R ¹ represents an optionally substituted phenyl group, an optionally substituted pyridyl group or an optionally substituted aralkyl group, R ² is a hydrogen atom, a C1-4 alkyl group,
C2-4 alkenyl group, C2-4 alkynyl group, C1-
4 haloalkyl group, C2-4 haloalkenyl group, C2-
4 haloalkynyl group, substituted phenyl C1-4 alkyl group, optionally substituted phenyl group, C1-4 alkoxy C1-4 alkyl group, C1-4 alkylthio C1
4 alkyl groups, C1-4 alkylsulfinyl C1-4
An alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkyl group or a C1-4 alkoxycarbonyl group,
X represents oxygen or NR ⁷ , R ⁷ is a hydrogen atom,
A C1-4 alkyl group, a C1-4 alkylcarbonyl group,
Optionally substituted phenylcarbonyl group or C1
~ 4 alkoxycarbonyl, R ³ , R ⁴ , R ⁵ and R ⁶ are each independently a hydrogen atom, a halogen atom,
C1-4 alkyl group, C1-4 haloalkyl group, C1
4 alkoxy groups, C1-4 haloalkoxy groups, C1-4
Alkylthio group, C1-4 rukylsulfinyl group, C1
To 4 alkylsulfonyl groups, optionally substituted phenyl groups, C1-4 alkylthio C1-4 alkyl groups, C
1-4 alkylsulfinyl C1-4 alkyl group, C1
~ 4 alkylsulfonyl C1-4 alkyl group, optionally substituted phenylthio C1-4 alkyl group, optionally substituted phenylsulfinyl C1-4 alkyl group, optionally substituted phenylsulfonyl C1-4
Alkyl group, C1-4 alkoxy C1-4 alkyl group,
Optionally substituted phenyl C1-4 alkyloxy C1-4 alkyl group, C1-4 alkylcarbonyloxy C1-4 alkyl group, hydroxy C1-4 alkyl group, di (C1-4 alkoxy) C1-4 alkyl group, C
1-4 alkoxycarbonyl group, cyano group, formyl group, hydroxyimino C1-4 alkyl group, C1-4 alkoxyimino C1-4 alkyl group, C2-4 alkenyloxyimino C1-4 alkyl group, C2-4 alkynyloxyimino C1-4 alkyl group, C1-4 haloalkoxyimino C1-4 alkyl group, C2-4 haloalkenyloxyimino C1-4 alkyl group or C2-4 haloalkynyloxyimino C1-4 alkyl group,
Also, R ³ , R ⁴ and R ⁵ , R ⁶ are taken together to form C 2
~ 5 alkylene chain may be formed, further R ⁴
And R ⁵ may combine together to form a single bond or a C1-4 alkylene chain. ] It is a substituted piperidinedione derivative represented by these, or its salt.

An optionally substituted phenyl group for R ¹ above,
As the pyridyl group which may be substituted, 2-substituted phenyl, 4-substituted phenyl, 2,4-disubstituted phenyl, 2,
3,4-trisubstituted phenyl 5-substituted-2-pyridyl,
3,5-disubstituted-2-pyridyl, 5,6-disubstituted-2-
Pyridyl, 3,4,5-trisubstituted-2-pyridyl, 6-
Substituted-3-pyridyl, 2,6-disubstituted-3-pyridyl,
4,6-di-substituted-3-pyridyl, 4,5,6-tri-substituted-3-pyridyl, 3-substituted-4-pyridyl group and the like can be mentioned.

Examples of the substituent of the phenyl group, pyridyl group and aralkyl group of R ¹ are halogen atoms such as fluorine, chlorine, bromine and iodine, OR ⁸ (R ⁸ is a C1-4 alkyl group, C2-4 alkenyl group). Group, C2-4 alkynyl group, C1-4 haloalkyl group, C2-4 haloalkenyl group, C2-4 haloalkynyl group, phenyl group, halogen-substituted phenyl group, C1-4 alkoxy-substituted phenyl group,
Phenyl C1-4 alkyl group, halophenyl C1-4 alkyl group, C1-4 alkoxy-substituted phenyl C1-4 alkyl group, C1-4 alkylthio C1-4 alkyl group,
C1-4 alkylsulfinyl C1-4 alkyl group, C
1-4 alkylsulfonyl C1-4 alkyl group, C1
4 alkoxy C1-4 alkyl group, C1-4 alkoxy C1-4 alkoxy C1-4 alkyl group, C1-4 alkoxycarbonyl C1-4 alkyl group, carboxy C1
~ 4 alkyl group, cyano C1-4 alkyl group, C1-4
Alkylcarbonyl represents a C1-4 alkyl group or a C3-6 cycloalkyl C1-4 alkyl group. However, the cycloalkyl group may contain 1 to 2 oxygen atoms),
C1-5 alkyl group, C2-4 alkenyl group, C2-4
Alkynyl group, C1-4 haloalkyl group, C2-4 haloalkenyl group, C2-4 haloalkynyl group, C1-4 alkoxy C1-4 alkyl group, C1-4 alkylthio C
1-4 alkyl group, C1-4 alkylsulfinyl C1
~ 4 alkyl group, C1-4 alkylsulfonyl C1-4
Alkyl group, S (O) mR ⁹ (R ⁹ is a C 1-4 alkyl group, a C 2-4 alkenyl group, a C 2-4 alkynyl group,
A C1-4 haloalkyl group, a C2-4 haloalkenyl group,
Phenyl group, halophenyl group, benzyl group, halobenzyl group, C1-4 alkylthio C1-4 alkyl group, C1
~ 4 alkylsulfonyl C1-4 alkyl group, C1-4
Alkoxy C1-4 alkyl group, alkoxy C1-4 alkoxy C1-4 alkyl group, C1-4 alkoxycarbonyl C1-4 alkyl group, carboxy C1-4 alkyl group, cyano C1-4 alkyl group, C1-4 alkylcarbonyl C1 4 alkyl group, m represents 0, 1 or 2), nitro group, C1-4 dialkylaminosulfonyl group, C1-4 alkylcarbonyl group, C1-4 alkoxycarbonyl group, CONR ²⁰ R ²¹ (R ²⁰ , R ²¹ Each independently represent a hydrogen atom, a C1-C4 alkyl group),
Carboxyl group, hydroxy group, cyano group, NR ¹⁰ R ¹¹
(R ¹⁰ and R ¹¹ are each independently a hydrogen atom, C1-4
Alkyl group, C1-4 alkoxy C1-4 alkyl group,
A C1-4 alkoxy group, a C1-4 alkylcarbonyl group, a C1-4 alkoxycarbonyl group, and a C1-4 alkylsulfonyl group are represented. ) And (halogen atom, C1
~ 4 alkyl group or C1-4 haloalkyl group) which may be substituted) pyridyloxy group.

The compound of the present invention can be produced by the following method. i)

[0005]

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(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ⁶ and X have the same meaning as described above, and Q represents a halogen atom, an alkylcarbonyloxy group, an alkoxycarbonyloxy group or a benzoyloxy group. ) In the first step, compounds [IVa] and [IVb]
Can be obtained by reacting compound [II] with R ¹ COQ in an equimolar amount, or by using an excess of either compound [II] or R ¹ COQ in the presence of an equimolar or more base. In the above reaction, examples of the base used include alkali metal hydroxides such as KOH and HaOH, alkali metal carbonates such as Na ₂ CO ₃ and K ₂ CO ₃ , Ca (OH) ₂ and Mg (OH) ₂ . Alkaline earth metal hydroxides, alkaline earth metal carbonates such as CaCO ₃ , tri (C 1 -C 6 alkyl) amines such as ethylamine and diethylisopropylamine, pyridine, piperidine, sodium phosphate, etc. , Water, methylene chloride, halogenated hydrocarbon solvents such as chloroform, aromatic hydrocarbons such as benzene, toluene, xylene, esters such as ethyl acetate, amides such as dimethylformamide, THF, dimethoxyethane, diethyl ether, etc. Ethers, acetonitrile and the like. The reaction proceeds smoothly at 0 ° C to 50 ° C, but the reaction may be performed in a two-phase system using a phase transfer catalyst such as a quaternary ammonium salt. Compounds [IVa] and [IVb
] Is a compound [II] and a compound R ¹ COOH
It can also be obtained by reacting in the presence of C. DC
Examples of the solvent used in the reaction with C include methylene chloride, chloroform, toluene, ethyl acetate, dimethylformamide, THF, dimethoxyethane, acetonitrile and the like. The reaction proceeds smoothly at -10 ° C to 50 ° C. The reaction mixture is worked up by conventional methods. Second
The rearrangement reaction of the step is carried out in the presence of a cyano compound and a mild base. The above compounds, for example 1 mol of the compounds [IVa] and [IVb], are added in an amount of 1 to 4 mol of base, preferably 1 to 2 mol of base, and 0.01 to 0.5 mol or more, preferably 0.1. React with 05 to 0.2 mole of cyanide compound. As the base used here, any of the above bases can be used. Further, as the cyan compound used, potassium cyanide, sodium cyanide, acetone cyanohydrin, hydrogen cyanide, a polymer holding potassium cyanide, or the like is used. The reaction can be completed in a shorter time by adding a small amount of a phase transfer catalyst such as crown ether. Reaction temperature is 80 ℃
It is carried out at lower temperatures, preferably 20 ° C to 40 ° C. The solvent used is 1,2-dichloroethane, toluene, acetonitrile, methylene chloride, ethyl acetate, dimethylformamide, methyl isobutyl ketone, TH
F, dimethoxyethane and the like.

Compound [I] can also be obtained by reacting compound [II] with R ¹ COCN in the presence of a base and, if desired, a Lewis acid according to the following method. Bases used include alkali metal hydroxides such as KOH and NaOH, Ca (OH) ₂ , Mg (O).
H) ₂ etc. alkaline earth metal hydroxides, triethylamine, diethyl isopropyl amine etc. tri (C 1 -C 2
6 alkyl) amine, piperidine, pyridine, sodium carbonate, sodium phosphate and the like. The Lewis acid is zinc chloride, aluminum trichloride or the like, preferably zinc chloride. The reaction is carried out in an organic solvent such as acetonitrile or methylene chloride at an appropriate temperature of -20 ° C to the boiling point of the solvent. Further, the compound [I] produced as described above can also be used to induce other desired compound [I] by the following method. ii)

[0007]

[Chemical 6]

Trione compound [I] produced by the above method
In an inert solvent in the presence of a halogenating agent such as phenyltrimethylammonium tribromide and a base, at a suitable temperature from 0 ° C to the boiling point of the solvent, preferably room temperature to 50 ° C.
The halogenated trione compound [Ia] can be produced by reacting for several hours to several tens of hours.
The solvent used in the reaction includes methylene chloride, benzene, ethyl acetate, THF, acetonitrile, dimethoxyethane and the like. Halogenated trione [Ia]
Can produce the desired compounds [Ib] and [Ic] by dehydrohalogenation in the presence of a base or by reaction with a nucleophilic reagent. iii)

[0009]

[Chemical 7]

The compound [Id] is the compound [Ie] (in the formula, R
³² represents a lower optionally branched alkoxy group, araalkyloxy group or acetoxy group. ) Is reacted with hydrohalic acid such as hydrochloric acid, hydrobromic acid, etc., trifluoroacetic acid, boron tribromide, etc., or by hydrogenolysis or alkaline hydrolysis, and then hydrolyzed as necessary. Can be manufactured. Further, the compound [Ie] is halogenated, alkylsulfonated or arylsulfonated by a conventional method to give a compound [If] (Z is a halogen atom, a leaving group such as an alkylsulfonate and an arylsulfonate). Represent.). This compound [If] in a solvent in the presence of a base in an equimolar amount or more,
Compound [I] can be produced by reacting at a temperature of 20 ° C. to the boiling point of the solvent used, preferably room temperature to 100 ° C. for 30 minutes to several tens of hours.
Examples of the base to be used include alkali metal hydroxides such as KOH and NaOH, hydroxides of alkaline earth metals such as Ca (OH) ₂ and Mg (OH) ₂ , and tri (ethylethylamine), diethyl isopropylamine and other tri ( C1-C6 alkyl) amine, piperidine, pyridine, DBU, KO ^t B
Examples thereof include organic bases such as u and Triton B, and alkali carbonates such as sodium carbonate and sodium phosphate. As the solvent, water, alcohol, methylene chloride, benzene, toluene, ethyl acetate, dimethylformamide, THF, dimethoxyethane, acetonitrile or the like can be used alone or in combination. iv)

[0011]

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(In the formula, R ³⁴ and R ³⁵ represent a C1 to C6 alkyl group, R ³³ represents an optionally substituted phenyl group, and R ³⁶ represents a hydrogen atom or a C1 to 4 alkyl group. , C
2-4 alkenyl group, C2-4 alkynyl group, C1-4
Haloalkyl group, C2-4 haloalkenyl group or C2
Represents to 4 haloalkynyl group, also, Y _1, Y ₂ represents a single bond or a substituted alkylene group may also be C1~4 that have. The compound [Ih] can be produced from the compound [Ig] by a known method, and the compound [Ik] is the compound [Ij] in an inert solvent in an amount of 2 equivalents or more, preferably 2-5. In the presence of an equal amount of a halogenating agent, the reaction is carried out in the temperature range from -20 ° C to the boiling point of the solvent used for several tens minutes to several tens hours to form a dihalogen compound. This dihalogen compound can be isolated, but usually, it is reacted without reaction in the presence of an acid in an inert solvent in the temperature range of 0 ° C. to the boiling point of the solvent to be used for the formyl compound [Ik]. Can be obtained. The halogenating agent used is chlorine, bromine, thionyl chloride, sulfuryl chloride, thionyl bromide, phosphorus pentachloride or the like, and the solvent is a chlorine-based solvent such as methylene chloride or chloroform, or a hydrocarbon such as benzene or toluene. , Ethers, ethyl acetate and the like are used. Further, in the hydrolysis, ethers such as dioxane, alcohols such as methyl alcohol, chlorine-based solvents such as methylene chloride and chloroform, hydrocarbons such as benzene and toluene are used together with water. The acid can be used in a catalytic amount to an excess amount, and examples thereof include hydrochloric acid, sulfuric acid, paratoluenesulfonic acid, and silica gel. Next, the compound [Ih] and the compound [Ik] are mixed in a solvent in an equimolar amount or more of R ³⁶ ONH ₂ (R ³⁶
Represents the same meaning as described above), in the presence of −20 ° C. to the boiling point of the solvent used, preferably from room temperature to 100 ° C.
Compound [Ii] and compound [Il] can be produced by reacting for 0 minutes to several tens of hours. still,
The reaction can be completed in a shorter time by adding a small amount of an acid catalyst such as sulfuric acid. Examples of the solvent used include water, alcohol, methylene chloride, benzene, toluene, ethyl acetate, dimethylformamide, THF, dimethoxyethane, acetonitrile and the like, alone or in a mixture.

The above R ¹ COQ (R ¹ and Q have the same meanings as described above) and R ¹ COOH (R ¹ has the same meanings as described above) can be produced according to known methods. . Further, the cyclic dione body represented by the general formula [II] can be produced according to the route shown below.

[0014]

[Chemical 9]

(In the formula, R ³⁰ and R ³¹ represent a C1 to C6 linear or branched alkyl group.) The compound [VII] is obtained from the compound [V] and R ₂ XNH ₂ by a known method. It is obtained by reacting the compound [VI] to be obtained with an equimolar or excess acid chloride R ³¹ O ₂ CCH ₂ COCl in a solvent in the presence of an equimolar or excess base. Bases used include alkali metal hydroxides such as KOH and HaOH, Ca (OH) ₂ , Mg (OH)
Alkaline earth metal hydroxides such as ₂ , Na ₂ CO ₃ , K
₂ CO ₃ and other alkali metal carbonates, CaCO ₃ , Mg
Alkaline earth metal carbonates such as CO ₃ and tri (C 1 -C 1) such as triethylamine and diethylisopropylamine
6 alkyl) amine, pyridine, sodium phosphate, etc., and the solvent used is methylene chloride, chloroform, toluene, ethyl acetate, dimethylformamide,
THF, dimethoxyethane, acetonitrile, etc. are used. The reaction is carried out between −10 ° C. and the boiling point of the solvent used.

Then, the obtained compound [VII] is added in an organic solvent at 0 ° C. to a solvent in the presence of an equimolar to 3-fold molar amount of an alkali metal alcoholate such as sodium ethylate or a metal hydride such as sodium hydride. After reacting between boiling points, the ester form [VIII] is obtained by neutralizing with an inorganic acid such as hydrochloric acid. As the solvent used in the reaction, alcohols such as ethanol and methanol, TH
Examples thereof include ethers such as F and dimethoxyethane, hydrocarbons such as toluene and xylene, and DMF. The obtained ester form [VIII] is methylene chloride, chloroform, toluene, ethyl acetate, dimethylformamide, THF, dioxane, dimethoxyethane, in the presence of water.
By heating in a solvent such as acetonitrile, the dione compound [IIa] is derived.

Further, the compound [IIb] is the compound [IIa]
Is a suitable base and an electrophilic reagent represented by R ³ Z;
It is obtained by reacting between 78 ° C. and the boiling point of the solvent used. Here, Z represents a suitable leaving group such as a halogen atom. Examples of the solvent used in this reaction include ether, THF, benzene, toluene, hexane and the like. Examples of the base include alkyl lithium and lithium diisopropylamide.

The acrylic acid derivative used as a raw material can be produced by a known method. Examples thereof will be shown below.

[0019]

[Chemical 10]

Halogenated acrylic acid derivative [V
a ′] (in the formula, R ³⁰ represents the same meaning as described above, R ³⁷ represents a leaving group such as chlorine and bromine), and mercaptans R ³⁸ SH (formula In the formula, R ³⁸ represents a lower alkyl group, an optionally substituted phenyl group or an optionally substituted arylalkyl group), and -1
The acrylic acid derivative [Va] can be produced by reacting in the temperature range from 0 ° C to the boiling point of the solvent used.

The acrylic acid derivative [Vb] can also be produced from the aldehydes by the Wittig reaction.

[0022]

[Chemical 11]

Starting compound [VIII] and compound of the present invention
[I] and [II] may have an optically active form, and more tautomeric forms, for example, a tautomeric formula,

[0024]

[Chemical 12]

It may exist in the form of All such forms are included within the scope of the present invention.

When the compound [I] contains a free hydroxyl group by the above method, a salt thereof, particularly an agro-horticulturally acceptable salt, an enamine or an analogue thereof, an acylate, Sulfonate, carbamate,
Ethers, thioethers, sulfoxides or sulfones and the like can be derived. Suitable agro-horticulturally acceptable salts include salts such as sodium, potassium, calcium and ammonium. An example of an ammonium salt is the formula: N + Ra Rb Rc Rd (wherein Ra, Rb, Rc and Rd each independently represent hydrogen and optionally a C1 to C10 alkyl group substituted by, for example, a hydroxy group). ) Ion and salt. Ra, Rb,
If either Rc or Rd is an optionally substituted alkyl group, then it is desirable that they contain from 1 to 4 carbon atoms. A suitable enamine or analog thereof has an OH moiety of the formula: --NReRf
(Wherein Re and Rf are each independently hydrogen or an optionally substituted alkyl group or aryl group having 1 to 6 carbon atoms, for example, a phenyl group), halogen, S (O) g. A compound converted to Rh (wherein Rh is, for example, an optionally substituted alkyl group or aryl group having 1 to 6 carbon atoms, for example, a phenyl group, and g represents 0 to 2). Is.

Suitable acylate, ether or carbamate derivatives have the OH moiety respectively represented by the formula: -OCOR
i, -ORj or -OCONRk Rl (wherein Ri and Rj have the same meanings as Rh above, and Rk and Rl have the same meanings as Re above). These derivatives can be manufactured by a conventional method. After the completion of the reaction, the target product can be obtained by performing a usual post-treatment. The structures of the compounds of the present invention are I
Determined from R, NMR and MS.

[0028]

EXAMPLES Next, the compounds of the present invention will be described in more detail with reference to examples. Example 1 Preparation of 3- (2-chloro-3-methoxy-4-methylsulfonylbenzoyl) -1-methoxypiperidine-2,4-dione

[0029]

[Chemical 13]

2.0 g (0.014 mol) of 1-methoxypiperidine-2,4-dione and 1.4 of triethylamine
g (0.014 mol) is dissolved in 20 ml of chloroform,
While cooling with ice, 4.0 g of 2-chloro-3-methoxy-4-methylsulfonylbenzoyl chloride was added dropwise. After dropping
The reaction was continued at room temperature for 1 hour. The reaction solution was washed with water and dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure to obtain 5.5 g of O-benzoyl compound. Next, the obtained O-benzoyl compound was dissolved in 50 ml of acetonitrile without purification, and 1.7 g of triethylamine was added, followed by 0.12 g (0.0014 mol) of acetone cyanohydrin.
Was added and reacted at room temperature for 5 hours. After the reaction was completed, the reaction solution was poured into 100 ml of ice water and acidified with diluted hydrochloric acid, and the liberated oily substance was extracted with 100 ml of chloroform. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography (chloroform: methanol =
19: 1) to obtain 4.1 g of the title compound as a powdery substance.

Example 2 3- (3-Methoxy-2-methyl-4-methylsulfonylbenzoyl) -1- (3-methoxy-2-methyl-4)
-Methylsulfonylbenzoyloxy) -6-methyl-
Production of 2,4-piperidinedione

[0032]

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2.3 g (0.016 mol) of 1-hydroxy-6-methyl-2,4-piperidinedione was dissolved in 20 ml of chloroform to obtain 3.2 g of triethylamine.
After adding (0.032 mol), 8.4 g (0.032 mol) of 3-methoxy-2-methyl-4-methylsulfonylbenzoyl chloride was added dropwise under ice cooling. After the dropping, the mixture was reacted at room temperature for 1 hour. After the reaction is completed, the reaction solution is
After washing with water and drying over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure to obtain 5.8 g of O-benzoyl compound. Next, the obtained O-benzoyl compound was dissolved in 50 ml of acetonitrile without purification, and triethylamine 1.
2 g and then 0.09 g of acetone cyanohydrin (0.0
014 mol) was added and the reaction was carried out at room temperature for 5 hours. After the reaction was completed, the reaction solution was poured into 100 ml of ice water and acidified with diluted hydrochloric acid, and the liberated oily substance was extracted with 100 ml of chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform: methanol = 100: 3) to give a brown powder.
4.1 g of the title compound was obtained as an r-like substance. H ¹ -NMR data (CDCl ₃ , δ ppm): 1.
48 (d, 3H) 2.29, 2.30 (s, 3H) 2.
65, 2.27 (s, 3H) 3.23 (s, 3H) 3.
25, 3.30 (s, 3H) 3.00, 3.32 (m,
2H) 3.92 (s, 3H) 3.92, 4.00 (s,
3H) 4.30 (m, 1H) 7.10 (d, 1H) 7.
82 (s, 1H) 7.84 (m, 2H) 16.46, 1
7.29 (bs, 1H)

Example 3 1-Hydroxy-3- (3-methoxy-2-methyl-4)
-Methylsulfonylbenzoyl) -6-methyl-2,4
-Preparation of piperidinedione 3- (3-methoxy-2-methyl-4-methylsulfonylbenzoyl) -1- (3-methoxy-2-methyl-4)
-Methylsulfonylbenzoyloxy) -6-methyl-
1.8 g (0.0030 mol) of 2,4-piperidinedione was dissolved in 10 ml of ethyl alcohol, 7 ml of 1N sodium hydroxide aqueous solution was added, and the mixture was reacted at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into ice water and acidified with diluted hydrochloric acid, and the liberated oily substance was extracted with 20 ml of chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform: methanol = 100: 3) to give a white powder.
0.9 g of the title compound was obtained as an r-like substance.

Example 4 Preparation of 5-bromo-1-methoxy-3- (2-nitro-4-trifluoromethylbenzoyl) -2,4-piperidinedione

[0036]

[Chemical 15]

Chloroform 20 was added to 1.7 g (0.0047 mol) of 1-methoxy-3- (2-nitro-4-trifluoromethylbenzoyl) -2,4-piperidinedione.
After dissolving in ml and adding 1.8 g (0.0047 mol) of phenyltrimethylammonium tribromide (PTAB), the reaction was carried out at room temperature for 24 hours. After completion of the reaction, the reaction solution was washed with an aqueous solution of sodium thiosulfate, washed with water, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off chloroform under reduced pressure was subjected to silica gel column chromatography (chloroform: methanol = 100: 3).
The title compound (2.0 g) was obtained as a white powder.

Example 5 Preparation of 1-methoxy-3- (2-nitro-4-trifluoromethylbenzoyl) piperidin-5-ene-2,4-dione 1-methoxy-3- (2-nitro-4-) Trifluoromethylbenzoyl) -2,4-piperidinedione 2.0 g
(0.0046 mol) was dissolved in 15 ml of methyl alcohol, a methyl alcohol solution of 28% sodium methylate was added dropwise, and the mixture was reacted at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into 20 ml of ice water, acidified with diluted hydrochloric acid, and the precipitate was extracted with 20 ml of chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure to obtain a solid residue. This one
Purification by recrystallization with methyl alcohol gave 1.2 g of the title compound as yellow crystals. Melting point 136-137 ° C

Example 6 6-formyl-1-methoxy-3- (3-methoxy-2)
-Methyl-4-methylsulfonylbenzoyl) piperidin-5-ene-2,4-dione

[0040]

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1-methoxy-3- (3-methoxy-2-
Methyl-4-methylsulfonylbenzoyl) -6-phenylthiomethyl-2,4-piperidinedione 9.0 g
(0.018 mol) was dissolved in 100 ml of chloroform, and at 0 ° C 5.2 g (0.038 mol) of sulfuryl chloride.
Was dripped. After returning to room temperature and reacting for 2 hours, chloroform was distilled off under reduced pressure, the residue was dissolved in 120 ml of dioxane, 20 ml of water and 10 g of silica gel were added, and the mixture was reacted under reflux for 4 hours. After completion of the reaction, the reaction solution was returned to room temperature, silica gel was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (benzene: ethyl acetate = 4: 1) to obtain 4.7 g of the title compound as a brown powder.

Example 7 Preparation of 6-difluoromethyl-1-methoxy-3- (3-methoxy-2-methyl-4-methylsulfonylbenzoyl) piperidin-5-ene-2,4-dione

[0043]

[Chemical 17]

6-formyl-1-methoxy-3- (3-
Methoxy-2-methyl-4-methylsulfonylbenzoyl) piperidine-5-ene-2,4-dione 1.0 g
(2.5 mmol) was dissolved in 15 ml of chloroform,
At -70 ° C, 0.45 g (2.8 mmol) of diethylaminosulfur trifluoride (DAST) was added dropwise. After completion of the dropping, the temperature was gradually returned to room temperature and the reaction was carried out at room temperature for 24 hours. After completion of the reaction, the reaction solution was poured into ice water and extracted with chloroform. The organic layer was washed with water, dried over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform: methanol = 19: 1) to give the title compound as a brown powder. 0.3 g was obtained.

Example 8 6-Ethoxyiminomethyl-1-methoxy-3- (3-
Preparation of methoxy-2-methyl-4-methylsulfonylbenzoyl) piperidin-5-ene-2,4-dione

[0046]

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6-formyl-1-methoxy-3- (3-
Methoxy-2-methyl-4-methylsulfonylbenzoyl) piperidine-5-ene-2,4-dione 0.50 g
(1.3 mmol) was dissolved in 5 ml of ethyl alcohol, 0.17 g (2.8 mmol) of methoxyamine was added, and the mixture was reacted at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into ice water and acidified with diluted hydrochloric acid, and then chloroform 20 ml
It was extracted with. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure to obtain a yellow solid. This solid was washed with methyl alcohol to obtain 0.4 g of the title compound as yellow crystals. Melting point 134-136 ° C

Example 9 Preparation of 3- (2-chloro-3-methoxy-4-methylsulfonylbenzoyl) -6-hydroxymethyl-1-methoxypiperidine-2,4-dione

[0049]

[Chemical 19]

1.3 g of 3- (2-chloro-3-methoxy-4-methylsulfonylbenzoyl) -1-methoxy-6-methoxymethylpiperidine-2,4-dione (0.
(0030 mol) was dissolved in a 33% hydrobromic acid-acetic acid solution and reacted at room temperature for 48 hours. After the reaction was completed, 20 ml of ice water was added to the reaction solution, and the mixture was extracted with 20 ml of chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate,
Chloroform was distilled off under reduced pressure to give crude 6-acetoxymethyl-3- (2-chloro-3-methoxy-4) as a brown powder.
1.3 g of -methylsulfonylbenzoyl) -1-methoxypiperidine-2,4-dione were obtained. Next, 1.3 g of the obtained crude acetoxy compound was dissolved in 10 ml of ethyl alcohol, 3 ml of a 2N sodium hydroxide aqueous solution was added, and the mixture was reacted at room temperature for 1 hour. After the reaction is complete, add 2 to the reaction mixture.
After neutralizing with N-hydrochloric acid, the mixture was extracted with 20 ml of chloroform. The residue obtained by the usual treatment was purified by silica gel column chromatography (chloroform: methanol = 19: 1) to obtain 0.73 g of the title compound as a pale yellow powder.

Example 10 Preparation of 2- (2-chloro-3-methoxy-4-methylsulfonylbenzoyl) -2-methoxy-2-azabicyclo [4.1.0] heptane-3,5-dione

[0052]

Embedded image

The 3- (2-chloro-3 obtained in Example 9
-Methoxy-4-methylsulfonylbenzoyl) -6-
Hydroxymethyl-1-methoxypiperidine-2,4-
0.73 g (1.74 mmol) of dione was dissolved in 15 ml of chloroform, and 0.19 g of triethylamine (1.
92 mmol), and then 0.33 g (1.92 mmol) of anhydrous methanesulfonic acid was added at room temperature. After reacting for 30 minutes at room temperature, the reaction solution was washed with water and dried over anhydrous magnesium sulfate. Chloroform was distilled off under reduced pressure to obtain a crude powder of crude 3- (2-chloro-3-methoxy-4-methylsulfonylbenzoyl) -1-methoxy-6-methylsulfonyloxymethylpiperidine-2,4-dione 1.
0 g was obtained. This product was dissolved in 10 ml of ethyl alcohol, 4 ml of 2N sodium hydroxide aqueous solution was added at room temperature, and the reaction was continued for 2 hours. After completion of the reaction, 2N-hydrochloric acid was added to the reaction solution under cooling for neutralization, and the precipitate was extracted with 20 ml of chloroform. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform: methanol = 19: 1) and described as a pale yellow powder. 0.15 g of compound was obtained.

Example 11 Preparation of 1-methoxy-2,4-piperidinedione

[0055]

[Chemical 21]

3-ethoxycarbonyl-1-methoxy-
2,4-piperidinedione 15.0 g (0.070 mol) was dissolved in acetonitrile 120 ml, and water 30 ml
After adding, the mixture was reacted under reflux for 2 hours. After completion of the reaction, the residue obtained by concentrating the reaction solution under reduced pressure was subjected to silica gel column chromatography (chloroform: methyl alcohol =
19: 1) and the title compound 8.5 as an oily substance.
g was obtained. (Reference example)

[0057]

[Chemical formula 22]

(1) Preparation of ethyl 3-methoxyaminopropionate 20.0 g (0.20 mol) of ethyl acrylate was dissolved in 80 ml of methyl alcohol, and methoxyamine 1 was added at 0 ° C.
After dropping 0.3 g (0.22 mol), the reaction was carried out at room temperature for 3 hours. After completion of the reaction, methyl alcohol was distilled off under reduced pressure to obtain 24.2 g of ethyl 3-methoxyaminopropionate as an oily substance.

(2) 2-Ethoxycarbonyl-N- (2
Preparation of -ethoxycarbonylethyl) -N-methoxyacetic acid amide Ethyl 3-methoxyaminopropionate 14.7 g
(0.10 mol) is dissolved in 150 ml of chloroform,
After adding 10.1 g (0.10 mol) of triethylamine, ethylmalonic acid chloride 15.1 at -10 to -5 ° C.
g (0.10 mol) was added dropwise. After the dropping, the mixture was reacted at room temperature for 30 minutes. After completion of the reaction, the reaction solution was washed with water and dried over anhydrous sodium sulfate, chloroform was distilled off under reduced pressure, and then 2-ethoxycarbonyl-N- (2-ethoxycarbonylethyl) -N-methoxyacetic acid amide 28.
0 g was obtained.

(3) Preparation of 3-ethoxycarbonyl-1-methoxy-2,4-piperidinedione 2-ethoxycarbonyl-N- (2-ethoxycarbonylethyl) -N-methoxyacetic acid amide 26.1 g (0.
10 mol) was dissolved in 80 ml of ethyl alcohol, and 2.8 g (0.12 mol) of sodium and 8 ml of ethyl alcohol were dissolved.
Sodium ethylate synthesized from 0 ml was added dropwise at room temperature and then reacted at room temperature for 6 hours. After completion of the reaction, ethyl alcohol was concentrated under reduced pressure and the residue was dissolved in 180 ml of water. The aqueous solution was washed with 50 ml of chloroform, neutralized with diluted hydrochloric acid under cooling, and the liberated oily substance was extracted with 150 ml of chloroform. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and chloroform was distilled off under reduced pressure to give 3-ethoxycarbonyl-1-methoxy- as an oily substance.
15.0 g of 2,4-piperidinedione was obtained.

Specific examples of the compounds produced as described in Reference Examples are shown in Table 1.

[0062]

[Table 1]

Next, the H ¹ -NMR data (CDCl ₃ , δppm) of the compound [V] and its precursor produced as described in Reference Example are shown below. (1-Methoxy-2,4-piperidinedione) 2.85 (t, 2H), 3.40 (s, 2H), 3.85 (s, 3H), 3.85 (t, 2H) (3-ethoxycarbonyl-1-methoxy-6) -Methyl-2,4-piperidinedione) 1.34 (d, 3H), 1.41 (t, 3H), 2.57 (dd, 1H), 2.94 (dd, 1H), 3.81
(s, 3H), 3.90 (m, 1H), 14.20 (s, 1H) (1-methoxy-6-methyl-2,4-piperidinedione) 1.40 (d, 3H), 2.67 (dd, 1H), 3.05 (dd, 1H), 3.43 (s, 2H), 3.94
(s, 3H), 4.16 (m, 1H) (3-ethoxycarbonyl-1-hydroxy-6-methyl-2,4-piperidinedione) 1.38 (d, 3H), 1.42 (t, 3H), 2.63 (dd , 1H), 3.00 (dd, 1H), 3.93
(m, 1H), 4.40 (q, 2H), 14.34 (s, 1H) (1-hydroxy-6-methyl-2,4-piperidinedione) 1.19 (d, 3H), 2.44 (dd, 1H), 2.84 (dd, 1H), 3.14 (d, 1H), 3.24
(d, 1H), 3.91 (m, 1H), 9.40 (bs, 1H) (6-ethyl-1-methoxy-2,4-piperidinedione) 1.31 (t, 3H), 1.37 (d, 3H), 2.62 (dd, 1H), 2.96 (dd, 1H), 3.32
(dd, 1H), 3.40 (d, 1H), 4.02 (m, 1H), 4.07 (q, 2H) (3-ethoxycarbonyl-1-methoxy-6-methoxymethyl-2,4-piperidinedione) 1.41 ( t, 3H), 2.95 (m, 2H), 3.38 (s, 3H), 3.60 (m, 2H), 3.81
(s, 3H), 3.85 (m, 1H), 4.15 (m, 1H), 4.37 (q, 2H), 14.36 (s, 1
H) Specific examples of compound [V] are shown in Table 1.

[0064]

[Table 1]

Next, specific examples of the compounds produced as described in Examples are shown in Tables 2 to 5.

[0066]

[Table 201]

[0067]

[Table 202]

[0068]

[Table 203]

[0069]

[Table 204]

[0070]

[Table 205]

[0071]

[Table 206]

[0072]

[Table 207]

[0073]

[Table 301]

[0074]

[Table 302]

[0075]

[Table 401]

[0076]

[Table 402]

[0077]

[Table 403]

[0078]

[Table 404]

[0079]

[Table 405]

[0080]

[Table 406]

[0081]

[Table 407]

[0082]

[Table 408]

[0083]

[Table 501]

[0084]

[Table 502]

[0085]

[Table 503]

[0086]

[Table 504]

[0087]

[Table 505]

Next, the H ¹ -NMR data (CDCl ₃ , δpp of the compound produced as described in the examples was obtained.
m) is shown below. The compound numbers correspond to the compound numbers shown in Tables 2 to 5. Compound number: (I-20) 1.40 (d, 3H) 2.30 (s, 3H) 2.54,2.85 (m, 2H) 3.30 (s, 3H) 3.99
(s, 3H) 4.12 (m, 1H) 7.10 (d, 1H) 7.87 (d, 1H) 16.10 (bs, 1H) 1
7.29 (bs, 1H) (I-22) 2.70,3.05 (t, 2H) 3.71,3.80 (t, 2H) 3.70,3.95 (s, 3H) 7.49
(d, 1H) 7.96 (bd, 1H) 8.50 (bs, 1H) 16.32 (bs, 1H) (I-24) 2.70,3.06 (t, 2H) 3.15 (s, 3H) 3.68,3.96 (s, 3H) 3.80,3.84
(t, 2H) 7.52 (d, 1H) 8.26 (d, 1H) 8.76 (bs, 1H) (I-28) 2.76,3.06 (m, 2H) 3.27,3.28 (s, 3H) 3.75 (s, 3H) 3.75,3.84
(m, 2H) 3.97 (s, 3H) 4.10 (s, 3H) 7.15 (d, 1H) 7.94 (d, 1H) 15.2
1 (bs, 1H) (I-30) 2.29,2.30 (s, 1H) 2.71,3.01 (m, 2H) 3.29 (s, 3H) 3.75 (s, 3H)
3.84 (m, 2H) 3.98 (s, 3H) 7.05 (d, 1H) 7.85 (d, 1H) 15.31 (bs, 1
H) (I-58) 1.42 (d, 3H) 2.83 (m, 2H) 3.28,3.30 (s, 3H) 3.75,3.96 (s, 3H)
4.10,4.12 (s, 3H) 7.15 (m, 1H) 7.95 (m, 1H) 16.83,17.50 (bs,
1H) (I-62) 3.17 (d, 2H) 3.72,4.00 (s, 3H) 3.95 (m, 1H) 4.3-4.9 (m, 2H) 7.
45 (d, 1H) 7.96 (bd, 1H) 8.48 (bs, 1H) (I-989 1.45,1.55 (m, 3H) 3.29 (s, 3H) 3.80 (m, 1H) 3.96 (m, 1H) 4.00
(bs, 3H) 4.10 (bs, 3H) 7.20 (m, 1H) 7.95 (m, 1H) 17.63,17.75
(bs, 1H) (I-108) 2.80 (m, 1H) 3.14 (m, 1H) 3.70 (m, 1H) 3.76 (m, 2H) 3.97 (s, 3H)
4.09 (s, 3H) 7.16 (m, 1H) 7.92 (d, 1H) (I-112) 2.75 (m, 1H) 3.15 (m, 1H) 3.40 (s, 3H) 3.55 (m, 1H) 3.70 (s , 3H)
3.99 (m, 2H) 7.50 (d, 1H) 7.95 (d, 1H) 8.50 (bs, 1H) 16.42 (bs,
1H) (I-114) 2.79 (m, 1H) 3.10 (m, 1H) 3.13 (s, 3H) 3.35 (bs, 3H) 3.55 (m, 1
H) 3.69 (s, 3H) 3.95 (m, 2H) 7.50 (d, 1H) 8.25 (d, 1H) 8.75 (bs,
1H) 16.30 (bs, 1H) (I-118) 3.08 (m, 2H) 3.29 (s, 3H) 3.36 (s, 3H) 3.69 (m, 1H) 3.75 (s, 3H)
4.10 (s, 3H) 7.15 (m, 1H) 7.95 (d, 1H) 16.92 (bs, 1H) (I-120) 2.29 (s, 3H) 3.38 (s, 3H) 3.75 (m, 2H) 4.00 (s , 3H) 4.10 (s, 3H)
7.09 (m, 1H) 7.88 (d, 1H) 16.85 (bs, 1H) (I-124) 3.16 (s, 3H) 3.35 (s, 3H) 3.68 (m, 1H) 3.74 (m, 1H) 3.98 (s , 3H)
4.04 (m, 2H) 7.60 (d, 1H) 8.30 (m, 1H) 8.77 (bs, 1H)

(II-12) 1.05-1.25 (m, 1H) 1.5-1.75 (m, 1H) 2.1-2.3 (m, 1H) 3.61 (m, 1
H) 3.75,4.04 (s, 3H) 7.43 (bd, 1H) 7.95 (d, 1H) 8.49 (bs, 1H) 1
6.69,17.84 (bs, 1H) (II-14) 1.1-1.3 (m, 1H) 1.7-2.4 (m, 2H) 3.15 (s, 3H) 3.63 (m, 1H) 3.75
(s, 3H) 3.80 (s, 1H) 4.05 (s, 1H) 7.50 (d, 1H) 8.25 (d, 1H) 8.75
(bs, 1H) 16.55 (bs, 1H) (II-18) 1.14,1.27 (m, 1H) 1.62 (m, 1H) 2.17,2.40 (m, 1H) 3.29 (m, 1H)
3.81,4.02 (s, 3H) 4.07,4.10 (s, 3H) 7.14 (d, 1H) 7.91 (d, 1H) (II-20) 1.15,1.25 (m, 1H) 1.62,1.71 (m, 1H) 2.25 (bs, 3H) 2.15,2.40
(m, 1H) 3.25 (s, 3H) 3.60,3.61 (m, 1H) 3.79,3.95 (s, 3H) 4.00
(s, 3H) 7.03 (d, 1H) 7.83 (d, 1H) 17.29,17.55 (bs, 1H)

(III-20) 2.26 (s, 3H) 2.46 (s, 3H) 3.26 (s, 3H) 3.97 (s, 3H) 5.97 (s, 1H)
7.05 (d, 1H) 7.86 (d, 1H) 9.87 (bs, 1H) (III-22) 3.90 (s, 3H) 6.05 (d, 1H) 7.45 (d, 1H) 7.66 (d, 1H) 7.99 (d , 1H)
8.50 (bs, 1H) (III-24) 3.16 (s, 3H) 3.91 (s, 3H) 6.06 (d, 1H) 7.54 (d, 1H) 7.70 (d, 1H)
8.29 (d, 1H) 8.77 (bs, 1H) (III-28) 2.32 (s, 3H) 3.26 (s, 3H) 3.95 (s, 3H) 5.95 (d, 1H) 7.72 (d, 1H)
7.86 (d, 1H) 14.72 (s, 1H) (III-30) 2.30 (s, 3H) 3.28 (s, 3H) 3.97 (s, 3H) 3.97 (s, 3H) 6.02 (d, 1H)
7.74 (d, 1H) 7.89 (d, 1H) 14.90 (s, 1H) (III-32) 2.42 (s, 3H) 3.87 (s, 3H) 5.89 (s, 1H) 7.45 (bs, 1H) 7.97 (bd , 1
H) 8.60 (bs, 1H) 14.08 (s, 1H) (III-36) 2.44 (d, 3H) 3.95 (s, 3H) 5.86 (s, 1H) 7.10 (m, 1H) 7.49 (m, 1H)
14.43 (s, 1H) (III-38) 2.44 (s, 3H) 3.28 (s, 3H) 3.95 (s, 3H) 3.98 (s, 3H) 5.88 (s, 1H)
7.07 (d, 1H) 7.88 (d, 1H) 14.73 (s, 1H) (III-39) 2.44 (s, 3H) 3.34 (s, 3H) 3.50 (s, 3H) 3.88 (m, 2H) 3.95 (s , 3H)
4.45 (t, 2H) 5.88 (s, 1H) 7.15 (d, 1H) 7.96 (d, 1H) 14.35 (s, 1
H) (III-40) 2.29 (s, 3H) 2.44 (s, 3H) 3.28 (s, 3H) 3.97 (s, 3H) 4.02 (s, 3H)
5.86 (s, 1H) 7.08 (d, 1H) 7.87 (d, 1H) 14.82 (s, 1H) (III-60) 2.30 (s, 3H) 3.39,3.50 (s, 3H) 3.97 (s, 3H) 4.03 (s, 3H) 6.35
(s, 1H) 6.75 (t; J = 53Hz, 1H) 7.09 (d, 1H) 7.90 (d, 1H) 14.90
(s, 1H) (III-74) 3.15,3.16 (s, 3H) 3.95,4.00 (s, 3H) 6.20,6.60 (s, 1H) 7.53
(bd, 1H) 8.33 (bd, 1H) 8.78 (bs, 1H) 10.03 (s, 1H) 14.02 (bs, 1
H) (III-80) 2.31,2.32 (s, 3H) 3.29 (s, 3H) 3.95,4.00 (s, 3H) 4.05,4.10
(s, 3H) 6.18,6.49 (s, 1H) 7.07,7.10 (d, 1H) 7.82,7.85 (d, 1
H) 10.09 (s, 1H) 14.78,14.80 (bs, 1H) (III-84) 3.18 (s, 3H) 3.52 (s, 3H) 3.90 (s.3H) 4.48 (s, 2H) 6.19 (s, 1H )
7.62 (d, 1H) 8.29 (d, 1H) 8.78 (s, 1H) 14.00 (s, 1H) (III-118) 1.34 (t, 3H) 2.44 (s, 3H) 3.28 (s, 3H) 4.10 (s , 3H) 4.16 (q, 2H)
5.86 (s, 1H) 7.14 (d, 1H) 7.95 (d, 1H) 14.35 (s, 1H) (III-119) 1.32 (t, 3H) 2.44 (s, 3H) 3.11,3.96 (s, 3H) 4.15 (q, 2H) 4.50
(t, 2H) 5.85 (s, 1H) 7.12 (d, 1H) 7.95 (d, 1H) 14.32 (s, 1H) (III-120) 1.34 (t, 3H) 2.32 (s, 3H) 2.47 (s, 3H) 3.28 (s, 3H) 3.99 (s, 3H)
3.99 (s, 3H) 4.14 (q, 2H) 5.82 (s, 1H) 7.09 (d, 1H) 7.86 (d, 1H)
14.72 (s, 1H) (III-148) 1.35 (t, 3H) 2.69 (s, 3H) 3.29 (s, 3H) 4.10 (s, 3H) 4.16 (q, 2H)
7.14 (d, 1H) 7.95 (d, 1H) 15.36 (s, 1H)

(IV-60) 2.27 (s, 3H) 3.26 (s, 3H) 3.94 (s, 3H) 3.98 (s, 3H) 4.12 (s, 3H)
6.55 (s, 1H) 7.06 (d, 1H) 7.86 (d, 1H) 8.15 (s, 1H) (IV-70) 1.37 (t, 3H) 2.26,2.28 (s, 3H) 3.26 (s, 3H) 3.93 (s, 3H) 3.96
(s, 3H) 4.36 (q, 2H) 6.55 (s, 1H) 7.06 (d, 1H) 7.86 (d, 1H) 8.16
(s, 1H) (IV-74) 1.36 (t, 3H) 3.16 (s, 3H) 3.86 (s, 3H) 4.36 (q, 2H) 6.57,7.26
(s, 1H) 7.54 (d, 1H) 8.29 (d, 1H) 8.77 (bs, 1H) (IV-110) 2.25,2.27 (s, 3H) 3.86 (s, 3H) 3.94,4.13 (s, 3H) 4.56,4.76
(d, 2H) 6.10 (m, 1H) 6.30 (m, 1H) 6.55 (s, 1H) 6.90,7.06 (d, 1
H) 7.80,7.86 (d, 1H) 8.15,8.17 (s, 1H) (IV-114) 3.16 (s, 3H) 3.87 (s, 3H) 4.75 (d, 2H) 6.14,6.40 (m, 1H) 6.55 ,
7.29 (s, 1H) 7.64 (d, 1H) 8.30 (d, 1H) 8.78 (s, 1H) 13.85 (bs, 1
H)

The compound of the present invention (the compound represented by the formula [I] or a salt thereof) exhibits a high herbicidal activity under the conditions of upland field, whether soil treatment or foliage treatment. Crabgrass, Echinocercules, Steller's clover, Sparrowgrass, Sparrowgrass,
Chickweed, polygonum, amaranthus, velvetleaf, white-tailed stag, American stag deer, morning glory, lobster, ragweed, tuna,
It shows high efficacy against various field weeds such as mosquitoes, sedges, yamgrass, and buckwheat corn, corn,
It also contains compounds that show selectivity for crops such as wheat, soybean, and cotton.

The compounds of the present invention are
It also has compounds that have excellent herbicidal activity against rice field weeds such as Mizuhigai, Konagi, Azena, Mizochabe, Chigusa, Matsuba, Urikawa and the like, and are selective to rice.

Further, the compound of the present invention can be applied to control weeds in orchards, lawns, railroad ends, vacant lots and the like.

The compounds of the present invention also include those having a plant growth regulating action, a bactericidal activity, and an insecticidal and acaricidal activity. The intermediate compounds of the compound of the present invention include those having herbicidal activity. Further, the compound of the present invention has a potential as a therapeutic drug for hypertyrosinemia.

[0096]

[Means for Solving the Problems]

[Herbicides] The herbicides of the present invention include one or two of the compounds of the present invention.
Contains at least one species as an active ingredient. When the compound of the present invention is actually applied, it can be used in a pure form without addition of other components, and can also be used in the form of general agricultural chemicals for the purpose of being used as agricultural chemicals, that is, wettable powder, granules, powders, It can also be used in the form of emulsion, water solvent, flowable, etc. When a solidifying agent is intended as an additive and a carrier, soybean flour, vegetable powder such as wheat flour, diatomaceous earth, apatite, gypsum, talc, bentonite, pyrophyllite, mineral fine powder such as clay, benzoic acid Organic and inorganic compounds such as soda, urea and mirabilite are used. For the purpose of liquid dosage form, kerosene, petroleum fractions such as xylene and solvent naphtha, cyclohexane, cyclohexanone, dimethylformamide, dimethyl sulfoxide, alcohol, acetone, trichloroethylene, methyl isobutyl ketone, mineral oil, vegetable oil, water. Etc. are used as a solvent. If necessary, a surfactant may be added in order to obtain a uniform and stable form in these preparations.

The concentration of the active ingredient in the herbicide of the present invention varies depending on the form of the above-mentioned preparation. For example, in the wettable powder, it is 5 to 90%, preferably 10 to 85%. : 3 to 70% in emulsion, preferably 5 to 30%, 0.01 to 30% in granule,
Preferably, a concentration of 0.05% to 10% is used.

The wettable powder and emulsion thus obtained are diluted with water to a predetermined concentration to give a suspension or emulsion, and the granules are sprayed onto the soil before or after germination of the weeds. It is mixed. In applying the herbicide of the present invention, an appropriate amount of 0.1 g or more of the active ingredient is applied per 10 ares.

Further, the herbicide of the present invention can be used by mixing with known fungicides, insecticides, acaricides, herbicides, plant growth regulators and the like. In particular, it is possible to reduce the dose used by mixing with a herbicide. or,
Not only can labor saving be achieved, but a higher effect can be expected due to the synergistic action of the mixed drugs. In that case, a combination with a plurality of known herbicides is also possible.

Suitable agents to be used in combination with the herbicide of the present invention include carbamate herbicides such as ventiocarve, molinate and dimepiperate, thiocarbamate herbicides, acid amide herbicides such as butachlor, pretilachlor and mefenacet, clomethoxynil, Diphenyl ether herbicides such as bifenox, triazine herbicides such as atrazine and cyanazine, sulfonylurea herbicides such as chlorsulfuron and sulfometuron-methyl, phenoxyalkanecarboxylic herbicides such as MCP and MCPB, and diclohop-methyl. Phenoxyphenoxypropionic acid herbicides, fluazifop-butyl and other pyridyloxyphenoxypropionic acid herbicides, trifluralin, pendimethalin and other dinitroaniline herbicides, and lini Ron, urea-based herbicides such as diuron, benzoyl prop ethyl, benzoylamino acid herbicides such as furan prop ethyl, imidazolinone herbicides such as imazaquin, Other, piperophos, daimuron, bentazone, die Fen zone coat,
Examples include naproanilide, etobenzanide, triazophenamide, quinclorac, and cyclohexanedione-based herbicides such as cetoxidim and cresodim.
It is also possible to add vegetable oils and oil concentrates to these combinations.

[0101]

【Example】

[Herbicides] Next, some formulation examples relating to the herbicides of the present invention will be shown, but the active ingredient compounds, additives and addition ratios are not limited to these examples, and can be varied within a wide range. Parts in the formulation examples indicate parts by weight.

Example 12 Wettable Powder Compound of the present invention 20 parts White carbon 20 parts Diatomaceous earth 52 parts Sodium alkylsulfate 8 parts The above components were uniformly mixed and finely ground to obtain a wettable powder with 20% of active ingredient. .

Example 13 Emulsion Compound of the present invention 20 parts Xylene 55 parts Dimethylformamide 15 parts Polyoxyethylene phenyl ether 10 parts The above components were mixed and dissolved to obtain an emulsion containing 20% of the active ingredient.

Example 14 Granules Compound of the present invention 5 parts Talc 40 parts Clay 38 parts Bentonite 10 parts Sodium alkylsulfate 7 parts The above components are uniformly mixed and finely pulverized to give a diameter of 0.5 to 1.
Granules having a particle size of 0 mm were obtained to obtain granules containing 5% of the active ingredient.

[0105]

Next, test examples relating to the effects of the herbicide of the present invention will be shown. The herbicidal effect was investigated according to the following criteria and expressed as a herbicidal index.

Survey Criteria Slaughter rate Slaughter index 0% 0 20-29% 2 40-49% 4 60-69% 680 80-89% 8 100% 10 Also, 1, 3, 5, 7, 9 Numerical values indicate intermediate values of 0 and 2, 2 and 4, 4 and 6, 6 and 8, and 8 and 10, respectively.

[0107]

[Equation 1]

Test Example 1 Stem and Leaf Spraying Pots having a surface area of 200 cm ² were filled with upland soil, and various cultivars of crabgrass, Inubiyu, velvetleaf and corn were sown on the surface layer, lightly covered with soil and then grown in a greenhouse. 250 pp prepared by diluting the emulsion shown in Example 13 of each test compound with water when each weed grew to a plant height of 5 to 10 cm.
The chemical solution of m was sprayed on the foliage of weeds with a small sprayer at a rate of 100 liter / 10a (corresponding to 25 g per 10a). After 3 weeks, the herbicidal effect and the phytotoxicity of corn were investigated, and the results are shown in Table 6.

[0109]

[Table 6]

Test Example 2 Treatment of Upland Soil A pot having a surface area of 250 cm ² was filled with upland soil, and seeds of Achinoe kurogosa, velvetleaf, foxtail millet and corn were sown. The next day, the diluting solution of the wettable powder shown in Example 12 was uniformly sprayed on the soil surface so that the active ingredient was 100 g per 10 a, and the herbicidal effect and the degree of phytotoxicity of corn were investigated 3 weeks after the treatment. The results are shown in Table 7.

[0111]

[Table 7]

Test Example 3 Paddy Field Stem and Leaf Treatment A pot having a surface area of 100 cm ² was filled with paddy field soil, and after scraping, seeds of Novier and Pleurotus cornucopia were sown, and then, 2-leaf stage rice was transplanted. This was grown in a greenhouse and when each weed reached the 1-1.5 leaf stage, the water depth was 3 cm.
After flooding with water, the diluted liquid of each test compound of the wettable powder shown in Example 12 was added dropwise so that the active ingredient was 6.25 g / 10a. Three weeks after the treatment, the herbicidal effect and the degree of phytotoxicity of rice were investigated, and the results are shown in Table 8.

[0113]

[Table 8]

[Table 506]

[Table 507]

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Takashi Kawana 345 Takada, Odawara-shi, Kanagawa Nippon Soda Co., Ltd. Odawara Research Institute

Claims (3)

[Claims] 1. A general formula [I]: (In the formula, R ¹ represents an optionally substituted phenyl group, an optionally substituted pyridyl group or an optionally substituted aralkyl group, R ² is a hydrogen atom, a C1-4 alkyl group,
C2-4 alkenyl group, C2-4 alkynyl group, C1-
4 haloalkyl group, C2-4 haloalkenyl group, C2-
4 haloalkynyl group, substituted phenyl C1-4 alkyl group, optionally substituted phenyl group, C1-4 alkoxy C1-4 alkyl group, C1-4 alkylthio C1
4 alkyl groups, C1-4 alkylsulfinyl C1-4
An alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkyl group or a C1-4 alkoxycarbonyl group,
X represents an oxygen atom or N—R ⁷ , and R ⁷ represents a hydrogen atom, a C1-4 alkyl group, a C1-4 alkylcarbonyl group, an optionally substituted phenylcarbonyl group or a C1-4 alkoxycarbonyl group. Represents R ³ , R ⁴ ,
R ⁵ and R ⁶ are each independently a hydrogen atom, a halogen atom, C1 -4 alkyl group, C1 -4 haloalkyl, C1 -4 alkoxy, C1 -4 haloalkoxy group, C1 -4 alkylthio group, C1 to 4 alkyl sulfinyl group, C1-4 alkylsulfonyl group, optionally substituted phenyl group, C1-4 alkylthio C1-4 alkyl group, C1-4 alkylsulfinyl C1-4 alkyl group, C1-4 alkylsulfonyl C1-4 Alkyl group, optionally substituted phenylthio C1-4 alkyl group, optionally substituted phenylsulfinyl C1
~ 4 alkyl group, optionally substituted phenylsulfonyl C1-4 alkyl group, C1-4 alkoxy C1-4
Alkyl group, optionally substituted phenyl C1-4 alkyloxy C1-4 alkyl group, C1-4 alkylcarbonyloxy C1-4 alkyl group, hydroxy C1
4 alkyl groups, di (C1-4 alkoxy) C1-4 alkyl groups, C1-4 alkoxycarbonyl groups, cyano groups,
Formyl group, hydroxyimino C1-4 alkyl group, C
1-4 alkoxyimino C1-4 alkyl group, C2-4
Alkenyloxyimino C1-4 alkyl group, C2-4
Alkynyloxyimino C1-4 alkyl group, C1-4
Haloalkoxyimino C1-4 alkyl group, C2-4 haloalkenyloxyimino C1-4 alkyl group or C
It represents 2-4 haloalkynyloxy imino C1~4 alkyl group and, R ^3, R ⁴ and R ^5, R ⁶ may form an alkylene chain of C2~5 together, further R ⁴ And R ⁵ together are a single bond or C1-4
You may form the alkylene chain of. ) A substituted piperidinedione derivative represented by: or a salt thereof. 2. A general formula [II]: (In the formula, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and X have the same meanings as described above.) A substituted piperidinedione derivative. 3. A compound represented by the general formula [I]: (Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and X
Represents the same meaning as described above. ) A herbicide containing one or more substituted piperidinedione derivatives represented by the formula (1) as an active ingredient.