JPH09216853A - Dihalophenylcabonate derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a dihalophenylcarbonate derivative expressed by a specific formula and useful as a synthetic intermediate of a new hydantoin derivative. SOLUTION: This derivative of formula I (X and Y are each a halogen; R' is a lower alkyl of >=2C or an aralkyl), preferably a compound of formula II (A is an amino or an isocyanate; R is a lower alkyl or an aralkyl), in concrete, 2-fluoro-4-chloro-5-ethoxycarbonyloxynitrobenzene, etc. Further, the compound is preferably obtained e.g. through a urea derivative produced by reducing a nitrobenzene derivative of formula III (R<5> is same as R) with hydrogen in the presence of a catalyst of platinum oxide, platinum-carbon or palladium- carbon to lead to an aniline derivative, further treating the aniline derivative with phosgene gas, and subsequently reacting with ammonia.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a dihalophenyl carbonate derivative useful as a synthetic intermediate for a novel hydantoin derivative.

[0002]

2. Description of the Related Art The present inventors have made the following general formula (1):

[0003]

Embedded image

[Wherein, X and Y each independently represent a halogen atom. R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group or an alkynyl group, and R ² represents a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group. R ³ and R ⁴ independently represent a hydrogen atom or a lower alkyl group. Has been found to have excellent herbicidal activity (see JP-A-63-183567).

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a dihalophenyl carbonate derivative useful as a synthetic intermediate for a novel hydantoin derivative.

[0006]

The present inventors have found that a dihalophenyl carbonate derivative represented by the following general formula is useful as a synthetic intermediate for the above hydantoin derivative, and completed the present invention. It was

That is, the present invention provides the following general formula (2)

[0008]

Embedded image

[In the formula, X and Y each independently represent a halogen atom, and Z represents a nitro group, an amino group, or an isocyanato group. R represents a lower alkyl group or an aralkyl group. And a dihalophenyl carbonate derivative represented by the formula:

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION In the above formula, examples of the halogen atom represented by X and Y include chlorine, bromine, fluorine and iodine. Examples of the lower alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, and a sec-butyl group.

The dihalophenyl carbonate derivative of the present invention can be produced by the following method.

[0012]

Embedded image

Wherein X and Y represent a halogen atom. R ⁵ is the same as R described above, and represents a lower alkyl group or an aralkyl group, and R ⁶ represents a lower alkyl group. R ³ and R ⁴ independently represent a hydrogen atom or a lower alkyl group. ].

That is, the nitrobenzene derivative (2a) is reduced in the presence of hydrogen using a catalyst of platinum oxide, platinum-carbon or palladium-carbon, and the aniline derivative (2b) is obtained.
Then, this can be converted to the isocyanate derivative (2c) by treating it with phosgene gas or trichloromethyl chloroformate. The urea derivative (3) is produced by reacting this isocyanate derivative (2c) with ammonia.

The urea derivative (3) can be derived into the hydantoin derivative represented by the general formula (6) according to the above scheme (see the reference example below).

Further, the hydantoin derivatives are represented by the following general formulas (A), (B),
The compounds (C) and (D) can be derived (see Reference Examples below).

[0017]

Embedded image

[0018]

[Chemical 6]

Wherein X, Y, R ¹ , R ² , R ³ and R ⁴
Represents the same meaning as described above, and Z represents a leaving group. ]

Table 1 shows an example of the hydantoin derivative represented by the above general formula (1) produced by the above method.

[0021]

[Table 1]

[0022]

Next, the present invention will be described in more detail with reference to Examples, Reference Examples and Test Examples.

Example 1

[0024]

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2-Fluoro-4-chloro-5-methoxycarbonyloxynitrobenzene (52.1 g, 0.2
Platinum dioxide (1.5 g) was added to a 4 mol) ethanol (600 ml) solution, and reacted at room temperature under a hydrogen atmosphere at normal pressure until the absorption of hydrogen gas ceased. After the completion of the reaction, the catalyst was separated by filtration, and the solvent was distilled off from the obtained pale yellow transparent solution under reduced pressure to obtain a pale red brown oily substance. This was almost pure 2-fluoro-4-chloro-5-
It was confirmed to be methoxycarbonyloxyaniline. This product can be purified by silica gel column chromatography, but can be used as it is in the next reaction. ¹ H-NMR (CDCl ₃ , TMS, ppm): δ 3.8
6 (3H, s), 4.13 (2H, brs), 6.4
8 (1H, d, J _HF = 8 Hz), 6.92 (1H, d,
J _HF = 10 Hz).

Embodiment 2

[0027]

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2-Fluoro-4-bromo-5-methoxycarbonyloxynitrobenzene (30.4 g, 0.1
mol) of ethanol (300 ml) was added with platinum dioxide (1.0 g), and the mixture was stirred under a hydrogen atmosphere until hydrogen absorption ceased. After completion of the reaction, the catalyst was filtered off, and the solvent was distilled off from the solution under reduced pressure to give 2-fluoro-
A brown solid of 4-bromo-5-methoxycarbonyloxyaniline (28.0 g) was obtained. ¹ H-NMR (CCl ₄ , TMS, ppm): δ 3.83
(3H, s), 5.01. (2H, brs), 6.6
3 (1H, d, J _HF = 7.6 Hz), 7.06 (1H,
d, J _HF = 9.8 Hz).

Example 3

[0030]

Embedded image

500 equipped with a dropping funnel and distillation apparatus
Trichloromethyl chloroformate (19 ml, 158 mmol) in ethyl acetate (200 m
l) Add solution and add 2-fluoro-4-chloro-5
-Methoxycarbonyloxyaniline (21.9 g, 1
00 mmol) in 100 ml of ethyl acetate.
Dropped in minutes. After completion of the dropwise addition, the mixture was heated to 80 ° C., and ethyl acetate was distilled off. After cooling, carbon tetrachloride (150 ml) was added, and the mixture was left overnight. After filtering off the insoluble matter, the solvent was distilled off from the filtrate under reduced pressure to give 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylisocyanate (2.
(0.6 g, 84% yield). ¹ H-NMR (CDCl ₃ , TMS, ppm): δ 3.8
8 (3H, s), 6.97 (1H, d), 7.37 (1
H, d). IR (KBr disk, cm ^-1 ): 2260,177
0.

Embodiment 4

[0033]

Embedded image

500 equipped with a dropping funnel and distillation apparatus
trichloromethyl chloroformate (15 ml, 125 mmol) in ethyl acetate (150 ml)
l) Add solution and add 2-fluoro-4-bromo-5
-Methoxycarbonyloxyaniline (28.0 g, 1
13 mmol) in ethyl acetate was added dropwise over 20 minutes.
After completion of the dropwise addition, the mixture was heated to 80 ° C., and ethyl acetate was distilled off. After allowing to cool, carbon tetrachloride (150 ml) was added, the insolubles were filtered off, and the solvent was distilled off from the filtrate under reduced pressure to give 2-fluoro-4-bromo-5-methoxycarbonyloxyphenylisocyanate (29.1 g). , 94% yield). ¹ H-NMR (CCl ₄ , TMS, ppm): δ 3.87
(3H, s), 6.89 ( 1H, d, J HF = 6.8H
z), 7.31 (1H, d, J _HF = 8.6 Hz). IR (KBr disk, cm ^-1 ): 2260,177
0.

Reference Example 1

[0036]

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2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl isocyanate (16.7)
g, 64 mmol) in benzene (300 ml).
Ammonia gas was introduced with vigorous stirring under ice cooling.
Immediately, precipitation of a white solid was observed. After 30 minutes, the precipitated solid was collected by filtration, sufficiently washed with benzene, and dried. This is the desired 2-fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (14.
2 g, 80% yield). ¹ H-NMR (CDCl ₃ -CD ₃ OD, TMS, pp
m): δ 1.37 (3H, t, J = 7.2 Hz),
4.30 (2H, q, J = 7.2 Hz), 7.10 (1
H, d, J _HF = 10.2 Hz), 8.07 (1H, d,
J _HF = 7.2 Hz).

Reference Example 2

[0039]

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2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl isocyanate (12.3
g, 50 mmol) in benzene (100 ml).
Ammonia gas was introduced with vigorous stirring under ice cooling.
After 30 minutes, the precipitated white solid was filtered, sufficiently washed with benzene, and dried. This was confirmed by NMR spectrum and the like to be the desired 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea (10.3 g, yield 78%). ¹ H-NMR (DMSO-d ₆ , TMS, ppm): δ
3.87 (3H, s), 5.81 (2H, br s),
7.12 (1H, d, J _HF = 10 Hz), 8.28 (1
H, d, J _HF = 7.2 Hz), 8.48 (1H, br)
s).

Reference Example 3

[0042]

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By the same operation as in Reference Example 2, 2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl isocyanate (47.7 g, 164 mmol) was added to
-Fluoro-4-bromo-5-methoxycarbonyloxyphenylurea (37.7 g, yield 75%) was obtained. ¹ H-NMR (CDCl ₃ -CD ₃ OD, TMS, pp
m): δ 3.83 (3H, s), 7.28 (1H,
d, J _HF = 10 Hz), 7.99 (1H, d, J _HF =
7.2 Hz).

Reference Example 4

[0045]

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2,4-Dichloro-5-methoxycarbonyloxynitrobenzene was used as a starting material and synthesized in the same manner as in Examples 1 to 4, 2,4-dichloro-5-methoxycarbonyloxyphenyl isocyanate (5.
04 g, 19.2 mmol) of benzene (120 ml)
Ammonia gas was introduced into the solution while stirring vigorously under ice cooling. After 30 minutes, the precipitated white solid was filtered and sufficiently washed with benzene. This was confirmed by ¹ H-NMR to be the desired 2,4-dichloro-5-methoxycarbonyloxyphenylurea (4.68 g, yield: 88%).
I confirmed more. ¹ H-NMR (CDCl ₃ -DMSO-d ₆ , TMS, pp
m): δ 3.88 (3H, s), 6.35 (2H, b
r), 7.45 (1H, s), 8.20 (1H, b
r), 8.32 (1H, s).

Reference Example 5

[0048]

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2-Fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (10.1 g, 36.4)
mmol) and a small excess of methyl 2-oxoisovalerate (5.2 g) in a solution of benzene (100 ml) in a catalytic amount of p-toluenesulfonic acid (60 mg, 0.35 mmol).
l) was added and the mixture was heated under reflux for 4 hours. After the reaction is completed, allow to cool,
The precipitated solid was separated by filtration. The filtrate was concentrated under reduced pressure to obtain a light brown oil. Recrystallization from ether-pentane gave a pale yellow solid (15.5 g). This thing is a cyclized product from ¹ H-NMR spectrum 3-
Although containing a small amount of (2'-fluoro-4'-chloro-5'-ethoxycarbonyloxyphenyl) -5-isopropylidenehydantoin, it is almost desired to obtain N- (2-fluoro-4-chloro-5-ethoxycarbonyloxy). Phenyl) -N '-(1'-methoxycarbonyl-2'-
Methyl-1′-propenyl) urea. This mixture was used for the next reaction without separation and purification.

Reference Example 6

[0051]

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N- (2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl) -N '-(1'-methoxycarbonyl-2'-methyl-1'-propenyl)
Urea (1.37 g, 3.5 mmol) in benzene (20
sodium acetate (300 mg) to the solution,
Heated to reflux for an hour. After the completion of the reaction, the precipitated sodium acetate was filtered off, and the filtrate was concentrated under reduced pressure. Recrystallized from ether-pentane solvent system, 3- (2'-fluoro-4'-
Chloro-5'-ethoxycarbonyloxyphenyl)-
A pale yellow individual of 5-isopropylidenehydantoin (1.
24 g, 96% yield). ¹ H-NMR (CDCl ₃ , TMS, ppm): δ
1.40 (3H, t, J = 6.8 Hz), 1.94 (3
H, s), 2.30 (3H, s), 4.35 (2H,
q, J = 6.8 Hz), 7.28 (1H, s), 7.4
1 (1H, d, J _HF = 2.8 Hz), 8.02 (1H,
brs).

Reference Example 7

[0054]

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3- (2'-fluoro-4'-chloro-
5′-ethoxycarbonyloxyphenyl) -5-isopropylidenehydantoin (204 mg, 0.57 mm)
ol) and sodium carbonate (50 mg) in methanol (20 ml) were stirred at 40 ° C. for 3 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added, and ether (5 m
1 × 3). The organic layer was washed with water and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solution was concentrated under reduced pressure to give a brown oil. Ether was added to this, and the precipitated white crystals (162 mg) were isolated by filtration. This compound was analyzed by NMR spectrum and the like to give 3- (2 ′
-Fluoro-4'-chloro-5'-hydroxyphenyl) -5-isopropylidenehydantoin (Compound 2)
Was confirmed. The physical properties of this compound are shown in Tables 2 and 3.

Reference Example 8

[0057]

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A 3- (2'-fluoro-
4′-chloro-5′-hydroxyphenyl) -5-isopropylidenehydantoin (25 mg, 91.7 μmo)
l) was added, and N, N-dimethylformamide (3 ml) was added and dissolved. Potassium carbonate (70 mg) and methyl iodide (100 μl) were added, and the mixture was stirred at 40 ° C. for 9 hours.
After the reaction was completed, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ether (3 ml × 3 times). Water layer (2m)
1 × 3 times) and dried over anhydrous magnesium sulfate.
The drying agent was removed, and a white solid precipitated by concentrating the ether solution under reduced pressure was isolated by filtration. This was 1-methyl-3- (2'-fluoro-4'-chloro-5'-methoxyphenyl) -5-isopropylidenehydantoin (compound 10), and the yield was 22 mg.
(80% yield). The physical properties of this compound are shown in Tables 2 and 3.

Reference Examples 9 to 19 Hydantoin derivatives of Compounds 1, 3 to 9 and 11 to 13 were produced from the urea derivative obtained in Reference Example according to the method described in the above Reference Example. Physical properties of these compounds are shown in Tables 2 and 3.

[0060]

[Table 2]

[0061]

[Table 3]

[0062]

[Table 4]

Formulation Example 1 (Granule) 5 parts of the compound of the present invention, 35 parts of pentonite, 55 talc
Parts and a mixture of 5 parts of sodium ligninsulfonate are uniformly mixed and pulverized, kneaded by adding water, granulated by an extrusion granulator, dried and sized to obtain granules.

Test Example 1 (Effect on Paddy Field Weeds) Paddy soil was filled in a Wagner pot of 1 / 5,000 are, and the seeds of millet, konjac, Scutellaria baicalensis and rice seedlings of 3 to 4 leaf stage (variety: Nihonbare) was sowed or transplanted to keep the water condition. Five days later, a predetermined amount of the herbicide, which was obtained by granulating the hydantoin derivatives 1 to 12 in accordance with Formulation Example 1, was subjected to water treatment in a predetermined amount so that the active ingredient became 20, 10, and 5 g per are. On the 30th day after the granule treatment, the herbicidal effect on the test plant and the phytotoxicity on the rice were investigated according to the following criteria, and the results in Table 4 were obtained.

[0065]

[0066]

[Table 5]

[0067]

[Table 6]

[Procedure amendment]

[Submission date] February 28, 1997

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Full text

[Correction method] Change

[Correction contents]

[Document Name] Statement

Title of the invention Dihalophenyl carbonate derivative

[Claims]

Embedded image [In the formula, X and Y each independently represent a halogen atom. R'represents a lower alkyl group having 2 or more carbon atoms or an aralkyl group. And a dihalophenyl carbonate derivative represented by the formula:

Embedded image [In the formula, X and Y each independently represent a halogen atom, and A represents an amino group or an isocyanato group. R represents a lower alkyl group or an aralkyl group. And a dihalophenyl carbonate derivative represented by the formula:

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a dihalophenyl carbonate derivative useful as a synthetic intermediate for a novel hydantoin derivative.

[0002]

2. Description of the Related Art The present inventors have made the following general formula (1):

[0003]

Embedded image

[Wherein, X and Y each independently represent a halogen atom. R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group or an alkynyl group, and R ² represents a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group. R ³ and R ⁴ independently represent a hydrogen atom or a lower alkyl group. Has been found to have excellent herbicidal activity (see JP-A-63-183567). In addition, as a compound related to the compound of the present invention, 2-fluoro-4-chloro-5-methoxycarbonyloxynitrobenzene is described in JP-A-58-83652. There is no description. Further, there is no description about amine derivatives and isocyanate derivatives.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a dihalophenyl carbonate derivative useful as a synthetic intermediate for a novel hydantoin derivative.

[0006]

The present inventors have found that a dihalophenyl carbonate derivative represented by the following general formula is useful as a synthetic intermediate for the above hydantoin derivative, and completed the present invention. It was

That is, the present invention provides the following general formula (2a)

[0008]

Embedded image

Wherein X and Y independently represent a halogen atom. R'represents a lower alkyl group having 2 or more carbon atoms or an aralkyl group. ] The dihalophenyl carbonate derivative shown by these, and the following general formula (2b)

[0010]

Embedded image

Wherein X and Y each independently represent a halogen atom, and A represents an amino group or an isocyanato group. R represents a lower alkyl group or an aralkyl group. And a dihalophenyl carbonate derivative represented by the formula:

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION In the above formula, examples of the halogen atom represented by X and Y include chlorine, bromine, fluorine and iodine. Examples of the lower alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-
Examples thereof include a butyl group.

The dihalophenyl carbonate derivative of the present invention can be produced by the following method.

[0014]

[Chemical 6]

Wherein X and Y each represent a halogen atom. R ⁵ is the same as R described above, and represents a lower alkyl group or an aralkyl group, and R ⁶ represents a lower alkyl group. R ³ and R ⁴ independently represent a hydrogen atom or a lower alkyl group. ].

That is, the nitrobenzene derivative (2a) is reduced in the presence of hydrogen using a catalyst of platinum oxide, platinum-carbon or palladium-carbon, and the aniline derivative (2a) is reduced.
b ′), and then can be converted to an isocyanate derivative (2b ″) by treating with phosgene gas or trichloromethyl chloroformate.
The urea derivative (3) is produced by reacting the isocyanate derivative (2b ″) with ammonia.

The urea derivative (3) can be derived into a hydantoin derivative represented by the general formula (6) according to the above-mentioned scheme (see Reference Example below).

Further, this hydantoin derivative is represented by the general formulas (A), (B),
The compounds (C) and (D) can be derived (see Reference Examples below).

[0019]

Embedded image

[0020]

Embedded image

Wherein X, Y, R ¹ , R ² , R ³ and R ⁴
Represents the same meaning as described above, and Z represents a leaving group. ]

Table 1 shows an example of the hydantoin derivative represented by the general formula (1) produced by the above method.

[0023]

[Table 1]

[0024]

Next, the present invention will be described in more detail with reference to Examples, Reference Examples and Test Examples.

Reference Example 1

[0026]

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A 3N round bottom flask (500 ml) equipped with a dropping funnel was charged with a 2N aqueous sodium hydroxide solution (350 ml).
ml) and 2-chloro-4-fluorophenol (59.2 g, 0.404 mol) was added with stirring. Then the solution was cooled in an ice-water bath and methyl chloroformate (52 ml, 63.6 g, 0.673 mol) was added dropwise with stirring. After completion of the dropwise addition, stirring was further continued, and the reaction was performed for a total of 1.5 hours. After completion of the reaction, the mixture was added to water and stirred sufficiently. The precipitated solid was filtered and sufficiently dried to give methyl (2-chloro-4-fluorophenyl) carbonate (45.9 g, yield: 55.5 g).
4%). ¹ H-NMR (CDCl ₃ , TMS, ppm): δ3.9
3 (3H, s), 6.9-7.4 (3H, m).

Reference Example 2

[0029]

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In a three-necked round bottom flask (2000 ml) equipped with a dropping funnel, a 2N aqueous sodium hydroxide solution (1.
5L) and 2-chloro-4-fluorophenol (260 g, 1.77 mol) were added with stirring. The solution was then cooled in an ice-water bath and ethyl chloroformate (216 ml, 245 g, 2.26 mol) was added dropwise with stirring. After completion of the dropwise addition, stirring was further continued, and the reaction was performed for a total of 4 hours. After completion of the reaction, chloroform was added to extract the product. The organic layer was dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the solvent was distilled off from the filtrate under reduced pressure to give ethyl (2-chloro-4-fluorophenyl) carbonate (364 g, yield: 94). .0
%) As a pale yellow transparent oil. This was used for the next reaction without purification. ¹ H-NMR (CDCl ₃ , TMS, ppm): δ1.3
7 (3H, t, J = 7.2 Hz), 4.28 (2H,
q, J = 7.2 Hz), 6.9-7.4 (3H, m).

Reference Example 3

[0032]

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In a three-necked round bottom flask (500 ml) equipped with a dropping funnel, methyl (2-chloro-4-fluorophenyl) carbonate (45.7 g, 0.223 mol) was added.
l) was added, 98% sulfuric acid (50 ml) was added, and the mixture was sufficiently stirred and suspended. The suspension was then cooled in an ice-water bath, and 98% sulfuric acid (25 ml) and 60% nitric acid (25 ml)
The mixed acid prepared from (1) and (2) was added dropwise at a rate such that the reaction temperature did not rise to room temperature or higher over about 1 hour with sufficient stirring. After the addition, the mixture was further stirred for 2 hours. The obtained reaction mixture was poured into ice water and stirred sufficiently. The precipitated solid was filtered and sufficiently dried to obtain a white solid of 2-fluoro-4-chloro-5-methoxycarbonyloxynitrobenzene (39.0 g, yield: 70.1%). ¹ H-NMR (CDCl ₃ , TMS, ppm): δ3.9
3 (3H, s), 7.40 (1H, d, J _HF = 10.5
Hz), 8.00 (1H, d, J _HF = 7.5 Hz).

Example 1

[0035]

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Three-necked round bottom flask equipped with a dropping funnel
(2000 ml) with ethyl (2-chloro-4-fluor).
Rophenyl) carbonate (364g, 1.67mo
l), add 98% sulfuric acid (200 ml) and stir thoroughly.
Stir to suspend. This suspension solution is then cooled in an ice water bath.
98% sulfuric acid (100 ml) and 60% nitric acid (100%)
ml) and the reaction temperature is above room temperature.
The mixture was added dropwise at a speed not to stir with sufficient stirring. Dripping
After that, stirring was further continued, and the whole was stirred for 8 hours. Obtained
The reaction mixture was poured into ice water and the precipitated solid was filtered.
2-fluoro-4-chloro-5
-Ethoxycarbonyloxynitrobenzene (149
g, yield: 33.9%) was obtained as a pale yellow solid.¹ H-NMR (CDCl_Three, TMS, ppm): δ1.4
1 (3H, t, J = 7.5Hz), 4.33 (2H,
q, J = 7.5 Hz), 7.48 (1H, d, J _HF= 1
0.0Hz), 8.03 (1H, d, J_HF= 7.5H
z).

Embodiment 2

[0038]

Embedded image

2-fluoro-4-chloro-5-methoxycarbonyloxynitrobenzene (52.1 g, 0.2
Platinum dioxide (1.5 g) was added to a 4 mol) ethanol (600 ml) solution, and reacted at room temperature under a hydrogen atmosphere at normal pressure until the absorption of hydrogen gas ceased. After the completion of the reaction, the catalyst was separated by filtration, and the solvent was distilled off from the obtained pale yellow transparent solution under reduced pressure to obtain a pale red brown oily substance. This was almost pure 2-fluoro-4-chloro-5-
It was confirmed to be methoxycarbonyloxyaniline. This product can be purified by silica gel column chromatography, but can be used as it is in the next reaction. ¹ H-NMR (CDCl ₃ , TMS, ppm): δ 3.8
6 (3H, s), 4.13 (2H, brs), 6.4
8 (1H, d, J _HF = 8.0 Hz), 6.92 (1H,
d, J _HF = 10.0 Hz).

Embodiment 3

[0041]

Embedded image

2-fluoro-4-bromo-5-methoxycarbonyloxynitrobenzene (30.4 g, 0.1
mol) of ethanol (300 ml) was added with platinum dioxide (1.0 g), and the mixture was stirred under a hydrogen atmosphere until hydrogen absorption ceased. After completion of the reaction, the catalyst was filtered off, and the solvent was distilled off from the solution under reduced pressure to give 2-fluoro-
A brown solid of 4-bromo-5-methoxycarbonyloxyaniline (28.0 g) was obtained. ¹ H-NMR (CCl ₄ , TMS, ppm): δ 3.83
(3H, s), 5.01. (2H, brs), 6.6
3 (1H, d, J _HF = 7.6 Hz), 7.06 (1H,
d, J _HF = 9.8 Hz).

Embodiment 4

[0044]

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A pressure-resistant glass autoclave (1000 m
1), 2-fluoro-4-chloro-5-ethoxycarbonyloxynitrobenzene (69.3 g, 0.263)
mol), ethanol (800 ml), and 5% platinum carbon (4.02 g) as a catalyst, and the inside of the vessel was sufficiently purged with hydrogen gas, followed by vigorous stirring under a hydrogen gas atmosphere at normal pressure. The reaction was carried out for 8 hours while supplying hydrogen gas as needed. After completion of the reaction, the catalyst was recovered by filtration, and the solvent was distilled off from the filtrate under reduced pressure to give a brown semi-solid 2-
Thus, fluoro-4-chloro-5-ethoxycarbonyloxyaniline (61.3 g, yield: 99.6%) was obtained. ¹ H-NMR (CDCl ₃ , TMS, ppm): δ1.3
7 (3H, t, J = 7.5 Hz), 3.60 (2H, b
rs), 4.25 (2H, q, J = 7.5 Hz), 6.
54 (1H, d, J _HF = 7.5 Hz), 6.97 (1
H, d, J _HF = 10.0 Hz).

Embodiment 5

[0047]

Embedded image

500 equipped with dropping funnel and distillation apparatus
Trichloromethyl chloroformate (1 ml)
9 ml, 158 mmol) of ethyl acetate (200 ml)
The solution was charged, and 2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (21.9 g, 100
mmol) in ethyl acetate (100 ml) was added dropwise over 20 minutes. After completion of the dropwise addition, the mixture was heated to 80 ° C., and ethyl acetate was distilled off. After cooling, carbon tetrachloride (150 ml) was added, and the mixture was left overnight. After insolubles were filtered off, the solvent was distilled off from the filtrate under reduced pressure to give 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylisocyanate (20.6
g, yield 84.0%). ¹ H-NM
R (CDCl ₃ , TMS, ppm): δ 3.88 (3
H, s), 6.97 (1H, d), 7.37 (1H,
d). IR (KBr disk, cm ^-1 ): 2260,177
0.

Example 6

[0050]

Embedded image

500 equipped with a dropping funnel and a distillation apparatus
trichloromethyl chloroformate (15 ml, 125 mmol) in ethyl acetate (150 ml)
l) Add solution and add 2-fluoro-4-bromo-5
-Methoxycarbonyloxyaniline (28.0 g, 1
13 mmol) in ethyl acetate was added dropwise over 20 minutes.
After completion of the dropwise addition, the mixture was heated to 80 ° C., and ethyl acetate was distilled off. After allowing to cool, carbon tetrachloride (150 ml) was added, the insolubles were filtered off, and the solvent was distilled off from the filtrate under reduced pressure to give 2-fluoro-4-bromo-5-methoxycarbonyloxyphenylisocyanate (29.1 g). , 94% yield). ¹ H-NMR (CCl ₄ , TMS, ppm): δ 3.87
(3H, s), 6.89 ( 1H, d, J HF = 6.8H
z), 7.31 (1H, d, J _HF = 8.6 Hz). IR (KBr disk, cm ^-1 ): 2260,177
0.

Embodiment 7

[0053]

Embedded image

Mitsuguchimaru equipped with a dropping funnel and a distillation device
Add trichlorochloroformate to the bottom flask (1000 ml).
Methyl (35 ml, 0.290 mol) and vinegar as solvent
Add ethyl acidate (400 ml), then 2-fluoro
-4-chloro-5-ethoxycarbonyloxyaniline
(61.3 g, 0.262 mol) of ethyl acetate (60
(ml) solution was added dropwise at room temperature with stirring. With dripping
At the same time, the generation of gas was observed, but the drip was continued.
After the completion of dropping, the mixture was further stirred. 2 hours from the start of dripping
After that, the reaction mixture is gradually warmed up and finally the solvent acetic acid is added.
The temperature was raised to a temperature at which ethyl could be distilled off (oil bath temperature: about 1
00 ° C). After distilling off ethyl acetate, bring the reaction mixture to room temperature.
After cooling, carbon tetrachloride was added and the mixture was left at room temperature. Insoluble matter
By filtering off and distilling off the solvent from the filtrate under reduced pressure,
2-Fluoro-4-chloro-5-ethoxy as a light brown solid
Carbonyloxyphenyl isocyanate is almost quantitative
I got it.¹ H-NMR (CDCl_Three, TMS, ppm): δ1.3
7 (3H, t, J = 7.2Hz), 4.27 (2H,
q, J = 7.2 Hz), 6.93 (1H, d, J _HF=
7.5 Hz), 7.22 (1H, d, J_HF= 9.0H
z).

Reference Example 4

[0056]

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2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl isocyanate (12.3)
g, 50 mmol) in benzene (100 ml).
Ammonia gas was introduced with vigorous stirring under ice cooling.
After 30 minutes, the precipitated white solid was filtered, sufficiently washed with benzene, and dried. The product was identified as the desired 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea (10.3 g, yield 78.0%) by NM.
It was confirmed from the R spectrum and the like. ¹ H-NMR (DMSO-d ₆ , TMS, ppm): δ
3.87 (3H, s), 5.81 (2H, br s),
7.12 (1H, d, J _HF = 10 Hz), 8.28 (1
H, d, J _HF = 7.2 Hz), 8.48 (1H, br)
s).

Reference Example 5

[0059]

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The same operation as in Reference Example 4 was carried out to give 2-fluoro-4-bromo-5-methoxycarbonyloxyphenylisocyanate (47.7 g, 164 mmol).
-Fluoro-4-bromo-5-methoxycarbonyloxyphenylurea (37.7 g, yield 75%) was obtained. ¹ H-NMR (CDCl ₃ -CD ₃ OD, TMS, pp
m): δ 3.83 (3H, s), 7.28 (1H,
d, J _HF = 10 Hz), 7.99 (1H, d, J _HF =
7.2 Hz).

Reference Example 6

[0062]

[Chemical 21]

Using 2,4-dichloro-5-methoxycarbonyloxynitrobenzene as a raw material, 2,4-dichloro-5-methoxycarbonyloxyphenyl isocyanate (5.
04 g, 19.2 mmol) of benzene (120 ml)
Ammonia gas was introduced into the solution while stirring vigorously under ice cooling. After 30 minutes, the precipitated white solid was filtered and sufficiently washed with benzene. This was confirmed by ¹ H-NMR to be the desired 2,4-dichloro-5-methoxycarbonyloxyphenylurea (4.68 g, yield: 88%).
I confirmed more. ¹ H-NMR (CDCl ₃ -DMSO-d ₆ , TMS, pp
m): δ 3.88 (3H, s), 6.35 (2H, b
r), 7.45 (1H, s), 8.20 (1H, b
r), 8.32 (1H, s).

Reference Example 7

[0065]

Embedded image

2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl isocyanate (16.7
g, 64 mmol) in benzene (300 ml).
Ammonia gas was introduced with vigorous stirring under ice cooling.
Immediately, precipitation of a white solid was observed. After 30 minutes, the precipitated solid was collected by filtration, sufficiently washed with benzene, and dried. This is the desired 2-fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (14.
2 g, 80% yield). ¹ H-NMR (CDCl ₃ -CD ₃ OD, TMS, pp
m): δ 1.37 (3H, t, J = 7.2 Hz),
4.30 (2H, q, J = 7.2 Hz), 7.10 (1
H, d, J _HF = 10.2 Hz), 8.07 (1H, d,
J _HF = 7.2 Hz).

Reference Example 8

[0068]

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2-fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (10.1 g, 36.4)
mmol) and a small excess of methyl 2-oxoisovalerate (5.2 g) in a solution of benzene (100 ml) in a catalytic amount of p-toluenesulfonic acid (60 mg, 0.35 mmol).
l) was added and the mixture was heated under reflux for 4 hours. After the reaction is completed, allow to cool,
The precipitated solid was separated by filtration. The filtrate was concentrated under reduced pressure to obtain a light brown oil. Recrystallization from ether-pentane gave a pale yellow solid (15.5 g). This thing is a cyclized product from ¹ H-NMR spectrum 3-
Although containing a small amount of (2'-fluoro-4'-chloro-5'-ethoxycarbonyloxyphenyl) -5-isopropylidenehydantoin, it is almost desired to obtain N- (2-fluoro-4-chloro-5-ethoxycarbonyloxy). Phenyl) -N '-(1'-methoxycarbonyl-2'-
Methyl-1′-propenyl) urea. This mixture was used for the next reaction without separation and purification.

Reference Example 9

[0071]

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N- (2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl) -N '-(1'-methoxycarbonyl-2'-methyl-1'-propenyl)
Urea (1.37 g, 3.5 mmol) in benzene (20
sodium acetate (300 mg) to the solution,
Heated to reflux for an hour. After the completion of the reaction, the precipitated sodium acetate was filtered off, and the filtrate was concentrated under reduced pressure. Recrystallized from ether-pentane solvent system, 3- (2'-fluoro-4'-
Chloro-5'-ethoxycarbonyloxyphenyl)-
A pale yellow individual of 5-isopropylidenehydantoin (1.
24 g, 96% yield). ¹ H-NMR (CDCl ₃ , TMS, ppm): δ
1.40 (3H, t, J = 6.8 Hz), 1.94 (3
H, s), 2.30 (3H, s), 4.35 (2H,
q, J = 6.8 Hz), 7.28 (1H, s), 7.4
1 (1H, d, J _HF = 2.8 Hz), 8.02 (1H,
brs).

Reference Example 10

[0074]

Embedded image

3- (2'-Fluoro-4'-chloro-
5′-ethoxycarbonyloxyphenyl) -5-isopropylidenehydantoin (204 mg, 0.57 mm)
ol) and sodium carbonate (50 mg) in methanol (20 ml) were stirred at 40 ° C. for 3 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added, and ether (5 m
1 × 3). The organic layer was washed with water and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the solution was concentrated under reduced pressure to give a brown oil. Ether was added to this, and the precipitated white crystals (162 mg) were isolated by filtration. This compound was analyzed by NMR spectrum and the like to give 3- (2 ′
-Fluoro-4'-chloro-5'-hydroxyphenyl) -5-isopropylidenehydantoin (Compound 2)
Was confirmed. The physical properties of this compound are shown in Tables 2 and 3.

Reference Example 11

[0077]

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A 3- (2′-fluoro-
4′-chloro-5′-hydroxyphenyl) -5-isopropylidenehydantoin (25 mg, 91.7 μmo)
l) was added, and N, N-dimethylformamide (3 ml) was added and dissolved. Potassium carbonate (70 mg) and methyl iodide (100 μl) were added, and the mixture was stirred at 40 ° C. for 9 hours.
After the reaction was completed, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ether (3 ml × 3 times). Water layer (2m)
1 × 3 times) and dried over anhydrous magnesium sulfate.
The drying agent was removed, and a white solid precipitated by concentrating the ether solution under reduced pressure was isolated by filtration. This was 1-methyl-3- (2'-fluoro-4'-chloro-5'-methoxyphenyl) -5-isopropylidenehydantoin (compound 10), and the yield was 22 mg.
(80% yield). The physical properties of this compound are shown in Tables 2 and 3.

Reference Examples 12 to 22 Hydantoin derivatives of Compounds 1, 3 to 9 and 11 to 13 were produced from the urea derivative obtained in Reference Example according to the method described in the above Reference Example. Physical properties of these compounds are shown in Tables 2 and 3.

[0080]

[Table 2]

[0081]

[Table 3]

[0082]

[Table 4]

Formulation Example 1 (granules) 5 parts of the compound of the present invention, 35 parts of pentonite, talc 55
Parts and a mixture of 5 parts of sodium ligninsulfonate are uniformly mixed and pulverized, kneaded by adding water, granulated by an extrusion granulator, dried and sized to obtain granules.

Test Example 1 (Effects on Paddy Field Weeds) Paddy soil was filled in a Wagner pot of 1 / 5,000 are, and seeds of barley, konjac, Scutellaria baicalensis and rice seedlings of 3 to 4 leaf stage (variety: Nihonbare) was sowed or transplanted to keep the water condition. Five days later, a predetermined amount of the herbicide, which was obtained by granulating the hydantoin derivatives 1 to 12 in accordance with Formulation Example 1, was subjected to water treatment in a predetermined amount so that the active ingredient became 20, 10, and 5 g per are. On the 30th day after the granule treatment, the herbicidal effect on the test plant and the phytotoxicity on the rice were investigated according to the following criteria, and the results in Table 4 were obtained.

[0085]

[0086]

[Table 5]

[0087]

[Table 6]

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Shoin Nagato 3-13-13-106, Kahama, Adachi-ku, Tokyo

Claims (1)

[Claims] 1. The following general formula: [In the formula, X and Y each independently represent a halogen atom, and Z represents a nitro group, an amino group, or an isocyanato group. R represents a lower alkyl group or an aralkyl group. And a dihalophenyl carbonate derivative represented by the formula: