JP2726404B2 - Substituted phenyl carbonate derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a substituted phenyl carbonate derivative useful as an intermediate for producing an N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative having excellent herbicidal activity.

[0002]

2. Description of the Related Art Conventionally, N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivatives having herbicidal activity, for example, N- (2-fluoro-4-chloro-5-isopropoxyphenyl)- 3,4,5,6-tetrahydrophthalimide (JP-B-63-20428) or N- (2-fluoro-4-chloro-5-alkyloxyphenyl) -3,4,5,6-tetrahydrophthalimide (particularly Japanese Unexamined Patent Publication No. 58-72563) is known. Also, the phenyl ring on the nitrogen atom is 2,4-
Compounds substituted by a dihalo-5-cycloalkyloxy group are described in JP-A-63-68562, 63-6.
Nos. 8563 and 63-280060 are described as examples.

Further, the present inventors have introduced a cycloalkyloxy group, particularly a cyclopentyloxy group, as a substituent at the 5-position of the phenyl ring in an N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative. As a result, it has been found that low dose treatment has a high herbicidal effect on weeds, and that phytotoxicity on major crops is significantly reduced.

[0004]

The present invention relates to the above-mentioned N-
An object of the present invention is to provide a substituted phenyl carbonate derivative useful as an intermediate for producing a substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies on a method for producing a tetrahydrophthalimide derivative, and as a result, have found that a substituted phenyl carbonate derivative is useful as an intermediate for the production thereof, and have reached the present invention. .

That is, the present invention provides a compound represented by the following general formula [I]

[0007]

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(Wherein R ¹ represents an isobutyl group, X represents a halogen atom, and Y represents a hydrogen atom, a nitro group or an amino group).

The substituted phenyl carbonate derivative of the present invention can be produced by the following synthetic route (see Examples).

[0010]

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(Wherein, R ¹ and X have the same meanings as described above.)

That is, a carbonate derivative [Ia] is obtained by reacting 2-chloro-4-fluorophenol with an alkyl chloroformate such as isobutyl chloroformate. By nitrating this carbonate derivative [Ia] with fuming nitric acid or the like, a nitrobenzene derivative [Ib] is obtained.
And Next, the aniline derivative [Ic] can be obtained by reducing the nitrobenzene derivative [Ib] using a catalyst such as palladium / carbon in the presence of hydrogen. In this case, when R ¹ is an isobutyl group, it is particularly preferable since the product of these steps becomes an oily substance or a low melting point solid.

Next, a method for producing an N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative using the compound of the present invention as a raw material will be described.

The N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative has the general formula [II]

[0015]

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(In the formula, R represents a cycloalkyl group having 3 to 8 carbon atoms, and X represents a halogen atom. The cycloalkyl group may be substituted with an alkyl group having 1 to 6 carbon atoms.) And an aniline derivative represented by 3,4,5,6-
It can be easily produced by reacting with tetrahydrophthalic anhydride in an inert solvent. As the inert solvent, a solvent such as benzene, toluene, xylene, chlorobenzene, and acetic acid, or a mixed solvent thereof can be used. The temperature of the reaction is selected from room temperature to 150 ° C., but it is preferable to carry out the reaction at 50 to 120 ° C. in terms of good yield. After the reaction, the target product can be easily isolated by ordinary post-treatment, and can be taken out as a pure product by recrystallization from an alcoholic solvent such as methanol.

The aniline derivative represented by the general formula [II] as a raw material can be produced from the above-mentioned aniline derivative [Ic], which is the compound of the present invention, by the following synthetic route.

[0018]

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(Wherein, R and X have the same meanings as described above. R ² represents an alkyl group having 1 to 6 carbon atoms, an allyl group having 3 to 4 carbon atoms, or an aralkyl group having 7 to 8 carbon atoms. Y represents a chlorine atom, a bromine atom, an iodine atom, a methylsulfonyloxy group or a p-toluenesulfonyloxy group.)

That is, the aniline derivative [Ic] of the present invention
In the presence of a base such as potassium carbonate, sodium carbonate, magnesium oxide or the like, acetonitrile, acetone, N, N-
The carbamate derivative [III] is derived by reacting with chloroformate in a solvent such as dimethylformamide. Next, the carbamate derivative [III] is treated in a protic solvent in the presence of a base such as sodium hydroxide or potassium carbonate to selectively hydrolyze only the carbonate group, thereby converting the carbamate derivative [III] to the phenol derivative [IV]. Is done. The obtained phenol derivative [IV]
And a compound represented by the general formula RY [V] in the presence of a base such as potassium carbonate, sodium carbonate, magnesium oxide or the like, whereby a cycloalkyloxy group can be introduced into the 5-position of the phenyl ring. The reaction is preferably carried out in a suitable solvent, and acetonitrile, acetone, methanol, ethanol, N, N-dimethylformamide and the like can be used. The carbamate derivative [VI] thus obtained is reacted, for example, in an aqueous sodium hydroxide solution to hydrolyze the carbamic acid ester, or when R ² in the general formula [VI] is, for example, a benzyl group. Hydrogenolysis using a catalytic reduction method using palladium carbon can lead to an aniline derivative represented by the general formula [II].

The aniline derivative represented by the general formula [Ic] as a raw material can be produced by the method shown in the following Reference Examples. The compound represented by the general formula [V] is a commercially available compound or a compound which can be easily prepared from a commercially available compound.

Further, N-substituted phenyl-3,4,5,6
The tetrahydrophthalimide derivative has the general formula [VII]

[0023]

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(Wherein, X has the same meaning as described above), and can also be produced by reacting a phenol derivative represented by the general formula [V]. In the reaction, acetonitrile, N, N-dimethylformamide, acetone, and the like were used in the presence of a base such as potassium carbonate, sodium carbonate, magnesium oxide, and sodium methoxide.
It is preferable to carry out in a solvent such as methanol.

The phenol derivative represented by the general formula [VII], which is a raw material for the reaction, is disclosed in JP-A-58-83672.
Although it is a compound described in Japanese Patent Application Laid-Open Publication No. H10-260, it can also be produced by the following synthetic route.

[0026]

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(In the formula, X and R ¹ represent the same meaning as described above.)

That is, by reacting the aniline derivative represented by the general formula [Ic] with 3,4,5,6-tetrahydrophthalic anhydride in an inert solvent such as benzene, toluene and acetic acid, The tetrahydrophthalimide derivative represented by the general formula [VIII] is led to a phenol represented by the general formula [VII] by selectively hydrolyzing the carbonate group at the 5-position of the phenyl ring in the presence of a base. Derivatives can be obtained. Examples of the base used include potassium carbonate, sodium carbonate, potassium hydroxide, and sodium hydroxide. The reaction is carried out in a protic solvent such as methanol, ethanol, or water at a temperature from room temperature to about 100 ° C. Is preferred in terms of good yield.

[0029]

The present invention will be described in more detail with reference to examples and reference examples, but the present invention is not limited to these examples.

Embodiment 1

[0031]

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In a 300 cc eggplant type flask equipped with a dropping funnel, 2-chloro-4-fluorophenol (2
9.3 g, 0.20 mol) and 2N-N under ice-cooling.
An aOH aqueous solution (100 ml) was added and stirred for 30 minutes. Then, isobutyl chloroformate (30 ml, d = 1.05)
(3,31.6 g, 0.23 mol) was added dropwise, and the mixture was stirred for 2 hours while gradually warming to room temperature. After the completion of the reaction, the mixture was extracted with methylene chloride (100 ml × 3 times) and dried over anhydrous magnesium sulfate. After removing the desiccant, the solvent and the like were distilled off under reduced pressure to give 2-chloro-4-fluorophenyl (isobutyl) carbonate as a colorless and transparent oil (45.8 g, 0.186 mmol, yield 93.0%). ) Got.

¹ H-NMR (CDCl ₃ , TMS, ppm): δ1.00 (6
H, d, J = 6.9Hz), 2.05 (1H, t & sep, J = 6.3 and 6.9Hz), 4.0
5 (2H, d, J = 6.3Hz), 6.8 ~ 7.3 (3H, m).

Next, fuming nitric acid (100 ml, 98%, d = 1.52) was put into a 200 cc eggplant-shaped flask, and 2-chloro-4-fluorophenyl (isobutyl) carbonate (10 g, 40 g) was added under ice cooling. (5 mmol) was added slowly. After stirring for 30 minutes, the reaction mixture was poured on ice. 2-fluoro-4-chloro-5 precipitated
A pale yellow solid of -isobutyloxycarbonyloxynitrobenzene was filtered and washed with water. After sufficiently drying, white crystals of the target compound (10.8 g, 36.9 mm
ol, yield 91.0%).

Melting point: 38.0-40.0.degree.¹ H-NMR (CDCl_Three, TMS, ppm): δ1.00 (6H, d, J = 6.9H
z), 2.07 (1H, t & sep, J = 6.3 and 6.9Hz), 4.07 (2H, d, J =
6.3Hz), 7.42 (1H, d, J_HF= 10.2Hz), 8.02 (1H, d, J _HF= 6.9
Hz).

The thus obtained 2-fluoro-4
-Chloro-5-isobutyloxycarbonyloxynitrobenzene (10 g, 34.3 mmol), toluene (100 ml) as solvent, and 10% Pd /
C (1.5 g) was charged into a 300 cc pressure-resistant glass autoclave. After sufficiently replacing the inside with hydrogen, stirring was started under a hydrogen pressure of 4 atm. An exotherm (up to about 50 ° C.) occurs with the progress of the reaction, but stirring is continued as it is.
Hydrogen was added as needed, and the mixture was stirred until absorption of hydrogen stopped. After the completion of the reaction, Pd / C was separated by filtration, and the released water was removed with a desiccant. By distilling off the solvent under reduced pressure, almost pure 2-fluoro-4-chloro-
5-isobutyloxycarbonyloxyaniline (9.
42 g) of a yellow oil was obtained quantitatively.

¹ H-NMR spectrum (CDCl ₃ , TMS, pp
m): δ1.00 (6H, d, J = 6.9Hz), 2.04 (1H, t & sep, J = 6.3a)
nd 6.9Hz), 4.04 (2H, d, J = 6.3Hz), 6.97 (1H, d, J _HF = 6.9
Hz), 7.24 (1H, d, J _HF = 9.0Hz).

Reference Example 1

[0039]

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The 2-fluoro-4-chloro-5-isobutyloxycarbonyloxyaniline obtained in Example 1 (6
5.0 g, 0.248 mol) and potassium carbonate (32
g, 0.232 mmol) in acetone (300 ml) was added to methyl chloroformate (23.4 g, 0.248 mol).
l) was added and the mixture was stirred under reflux for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, 1N hydrochloric acid (300 ml) was added, and the precipitated solid was collected by filtration. This was thoroughly washed with water and dried to give N- (2-fluoro-4-chloro-5.
-Isobutyloxycarbonyloxyphenyl) methyl carbamate as white crystals (56.6 g, yield 71.4).
%).

Melting point: 72.2-78.8 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ1.00 (6H,
d, J = 6.5Hz), 2.05 (1H, t & sep, J = 6.5Hz), 3.78 (3H, s), 4.03
(2H, d, J = 6.5Hz), 6.85 (1H, brs), 7.08 (1H, d, J _HF = 10.2H
z), 8.10 (1H, d, J _HF = 7.5 Hz). IR spectrum (KBr disk, cm ^-1 ): 1773,1733,1545,128
5,1235,1180.

The N- (2-fluoro-4- obtained above
Methyl chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (14.0 g, 43.8 mmol)
l) was dissolved in methanol (100 ml), and potassium carbonate (7.26 g, 52.3 mmol) was added thereto.
The reaction was carried out at a temperature of 3 ° C. for 3 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and acetic acid (20 ml) was added to the obtained solid to dissolve it. This was poured into ice water, and the precipitated solid was isolated by filtration. After sufficiently washing with water and drying, white crystals of methyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (9.
60 g, 43.7 mmol, 99.8% yield).

Melting point: 140.0 to 141.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ1.57 (3H,
s), 3.78 (3H, s), 5.53 (1H, s), 6.75 (1H, br s), 7.05 (1H, d, J
_HF = 10.5Hz), 7.82 (1H, d, J _HF = 7.5Hz). IR spectrum (KBr disk, cm- ¹ ): 3440,1717,1630,156
0,1430,1250.

The N- (2-fluoro-4- obtained above
Methyl chloro-5-hydroxyphenyl) carbamate (5.0 g, 22.8 mmol) and potassium carbonate (3.
89 g, 28.1 mmol) of acetonitrile (50 m
l) The solution was stirred under reflux for 1 hour. Next, bromocyclopentane (4.07 g, 27.3 mmol) was added dropwise, and the mixture was further reacted for 3 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the mixture was acidified with 1N hydrochloric acid (100 ml), and extracted with ethyl acetate (100 ml × 3 times). The organic layer was washed with water, dried and the solvent was distilled off under reduced pressure to give N- (2-fluoro-4-chloro-5-
Methyl (cyclopentyloxyphenyl) carbamate (5.56 g, 19.3 mmol, yield 84.7%) was obtained.

Melting point: 120.0-123.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.40-2.1
0 (8H, m), 3.77 (3H, s), 4.77 (1H, m), 6.82 (1H, br s), 7.07 (1
H, d, J _HF = 10.5Hz), 7.83 (1H, d, J _HF = 7.5Hz). IR spectrum (KBr disk, cm ^-1 ): 1714,1535,1500,141
5,1255,1190.

The thus obtained N- (2-fluoro-4)
Ethyl alcohol (30 ml) and 2N aqueous sodium hydroxide solution (50 ml) were added to methyl-chloro-5-cyclopentyloxyphenyl) carbamate (5.75 g, 20.0 mmol), and the mixture was heated with stirring in a 110 ° C. oil bath for 4 hours. did. After completion of the reaction, the solvent was distilled off and ethyl acetate (10
(0 ml × 3 times). Wash the organic layer with saturated saline,
After drying, the solvent was distilled off under reduced pressure to give oily 2-
Fluoro-4-chloro-5-cyclopentyloxyaniline (4.36 g, 19.0 mmol, yield 95.0%)
I got The spectrum data and the like are as shown in Reference Example 2.

Reference Example 2

[0048]

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2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (22.0 g, 100 mmol
l) and potassium carbonate (13.8 g, 100 mmol) in acetone (300 ml) were mixed with ethyl chloroformate (1).
(6.3 g, 150 mmol) and stirred at 60 ° C. for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and 1N hydrochloric acid (1
And then acidified, and then ethyl acetate (100 ml × 3).
Times). The organic layer was washed with water, dried, and the solid precipitated by distilling off the solvent under reduced pressure was collected by filtration. This was recrystallized from chloroform-hexane to give N-
White crystals of ethyl (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (2
(3.3 g, yield: 80.2%).

Melting point: 143.8 to 147.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.13 (3H, t, J
= 6.5Hz), 3.92 (3H, s), 4.23 (2H, q, J = 6.5Hz), 6.80 (1H, br
s), 7.15 (1H, d, J _HF = 10.5 Hz), 8.12 (1 H, d, J _HF = 8.0 Hz). IR spectrum (KBr disk, cm ^-1 ): 1770, 1730, 1545, 129
0,1235,1215.

To the obtained ethyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (45.2 g, 155 mmol), potassium carbonate (21.4 g, 155 mmol) and methanol (1
00 ml) and reacted for 2 hours while heating under reflux. After completion of the reaction, the mixture is cooled to room temperature, and the solvent is distilled off under reduced pressure.
Hydrochloric acid (300 ml) was added to make it acidic, and ethyl acetate (10
(0 ml × 3 times). The organic layer was washed with water, dried, and the solvent was distilled off under reduced pressure. The precipitated solid was collected by filtration. This was recrystallized from chloroform-hexane to give N-
White crystals of ethyl (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (35.2 g, yield 97%) were obtained.

Melting point: 151.5 to 154.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.32 (3H, t,
J = 7.2Hz), 4.23 (2H, q, J = 7.2Hz), 5.84 (1H, s), 6.80 (1H, br
s), 7.04 (1H, d, J _HF = 10.5 Hz), 7.85 (1 H, d, J _HF = 7.5 Hz). IR spectrum (KBr, cm ^-1 ): 3440, 1710, 1560, 1430, 125
0.

Next, the obtained N- (2-fluoro-4-
Ethyl chloro-5-hydroxyphenyl) carbamate (10.0 g, 42.8 mmol) and potassium carbonate (8.0).
87 g, 64.2 mmol) of acetonitrile (150
ml) The solution was stirred at 80 ° C. for 1 hour. Next, cyclopentyl bromide (9.57 g, 84.2 mmol) was added dropwise, and the mixture was further reacted for 7 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the mixture was acidified with 1N hydrochloric acid (100 ml), and extracted with ethyl acetate (100 ml × 3 times).
The organic layer was washed with water, dried, and the solvent was distilled off under reduced pressure to give ethyl N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate (1
2.7 g, 98% yield).

Melting point: 92.8-97.8 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.33 (3H,
(t, J = 7.0Hz), 1.40-2.10 (8H, m), 4.32 (2H, q, J = 7.0Hz), 4.8
8 (1H, m), 6.87 (1H, br s), 7.15 (1H, d, J _HF = 10.5Hz), 7.92 (1
H, d, J _HF = 7.0Hz). IR spectrum (KBr, cm ^-1 ): 1710,1535,1495,1415,125
Five.

In this reaction, even if cyclopentyl p-toluenesulfonate was used in place of cyclopentyl bromide, the reaction proceeded similarly, and the desired N- (2-
Ethyl fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate was obtained in a yield of 95%.

N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) thus obtained
Ethyl alcohol (50 ml) and a 2N aqueous solution of sodium hydroxide (100 ml) were added to ethyl carbamate (12.7 g, 42.1 mmol).
The mixture was heated and stirred for hours. After completion of the reaction, the solvent was distilled off, and extracted with ethyl acetate (100 ml × 3 times). The organic layer was washed with brine, dried, and evaporated under reduced pressure to give oily 2-fluoro-4-chloro-5-cyclopentyloxyaniline (9.36 g, 40.8 mmol, yield 97).
%).

¹ H-NMR spectrum (CDCl ₃ , TMS, pp
m): δ1.40 ~ 2.07 (8H, m), 3.72 (2H, brs), 4.57 (1H, m), 6.
35 (1H, d, J _HF = 8.0 Hz), 6.98 (1 H, d, J _HF = 10.5 Hz). IR spectrum (KBr disk, cm ^-1 ): 2980, 1635, 1510, 142
3,1250,1190.

Reference Example 3

[0059]

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The N- produced by the method shown in Reference Example 2
Ethyl (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (1.45 g,
4.97 mmol) and potassium carbonate (1.03 g, 7.4)
(6 mmol) in ethanol (5.0 ml) was stirred under reflux for 1 hour and then cyclopentyl bromide (1.
11 g, 7.46 mmol) was added and the mixture was further stirred for 2 hours. After completion of the reaction, the mixture was poured into 1N hydrochloric acid (50 ml) and extracted with ethyl acetate (50 ml × 3 times). The organic layer was dried and concentrated under reduced pressure to give off-white crystals of ethyl N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate (1.41 g, 4.6).
9 mmol, yield 94.4%). The spectrum data and the like are as shown in Reference Example 2.

Reference Example 4

[0062]

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2-fluoro-4-chloro-5-cyclopentyloxyaniline (0.50 g, 2.18 mmol)
l) and 3,4,5,6-tetrahydrophthalic anhydride (0.398 g, 2.61 mmol) in acetic acid (3.0
ml) The solution was stirred under reflux for 3 hours. Water (20 ml) was added to the obtained reaction mixture, and ethyl acetate (20 ml ×
3 times). After drying the organic layer, the solvent was distilled off under reduced pressure, and the obtained pale yellow oil was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 8 /
Purified in 1) and N- (2-fluoro-4-chloro-5-
Colorless and transparent oily product of cyclopentyloxyphenyl) -3,4,5,6-tetrahydrophthalimide (0.513
g, 1.41 mmol, 65% yield). This was added with ethanol (1.0 ml) and recrystallized to obtain a white solid.

Melting point: 69.0-75.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.30-
2.10 (12H, m), 2.40 (4H, m), 4.68 (1H, m), 6.75 (1H, d, J _HF = 7.
0 Hz), 7.20 (1H, d, J _HF = 9.0 Hz). IR spectrum (KBr disk, cm ^-1 ): 1725, 1505, 1430, 138
5,1200.

Reference Example 5

[0066]

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The N- produced by the method shown in Reference Example 1
Methyl (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (5.3
7 g, 16.8 mmol) and 3-methylcyclopentyl p-toluenesulfonate (5.0 g, 20.2 mmol)
l) and potassium carbonate (2.32 g, 16.8 mmol)
A solution of 1) in methanol (50 ml) was stirred under reflux for 5 hours. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid (100 m
l) and extracted with ethyl acetate (50 ml x 3). After drying the organic layer, the solvent was distilled off under reduced pressure to give off-white crystals of methyl N- {2-fluoro-4-chloro-5- (3-methylcyclopentyl) oxyphenyl} carbamate (3.81 g). , 12.6 mmol, yield 75.2%).

¹ H-NMR spectrum (CDCl ₃ , TMS, pp
m): δ1.02 and 1.08 (total 3H, d, J = 6.0Hz), 1.25 ~ 2.40
(7H, m), 3.77 (3H, s), 4.75 (1H, m), 6.68 (1H, brs), 7.05 (1
H, d, J _HF = 10.5Hz), 7.75 (1H, d, J _HF = 7.5Hz).

Next, the obtained methyl N- {2-fluoro-4-chloro-5- (3-methylcyclopentyl) oxyphenyl} carbamate (3.45 g, 11.4 mmol)
Ethyl alcohol (20 ml) and a 2N aqueous sodium hydroxide solution (30 ml) were added to 1), and the mixture was stirred under reflux for 3 hours. After completion of the reaction, the reaction mixture was directly extracted with ethyl acetate (50 ml × 3 times). The organic layer was washed with a saturated saline solution, dried, and then the solvent was distilled off under reduced pressure.
-Fluoro-4-chloro-5- (3-methylcyclopentyl) oxyaniline (1.77 g, 7.26 mmol)
1, yield 63.6%).

¹ H-NMR spectrum (CDCl ₃ , TMS, pp
m): δ1.02 and 1.10 (total 3H, d, J = 6.0Hz), 1.22 ~ 2.58
(7H, m), 3.75 (2H, br s), 4.65 (1H, m), 6.33 (1H, d, J _HF = 8.0H
z), 6.98 (1H, d, J _HF = 10.0Hz).

Reference Example 6

[0072]

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2-fluoro-4-chloro-5- (3-methylcyclopentyl) oxyaniline (1.76 g,
A solution of 7.22 mmol) and 3,4,5,6-tetrahydrophthalic anhydride (1.32 g, 8.68 mmol) in acetic acid (15 ml) was stirred under reflux for 4 hours. The obtained reaction mixture was added to 1N hydrochloric acid (50 ml) and extracted with ether (50 ml × 3 times). After drying the organic layer, the solvent was distilled off under reduced pressure, and the obtained reddish brown oil was purified by silica gel column chromatography (developing solvent: hexane / ethyl acetate = 8/1). By recrystallizing the obtained N- {2-fluoro-4-chloro-5- (3-methylcyclopentyl) oxyphenyl} -3,4,5,6-tetrahydrophthalimide as a colorless transparent oil from methanol, White solid (0.93 g, 2.38 mm
ol, yield 33.0%). Melting point: 68.0-70.0 ° C ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.01 a
nd 1.08 (total 3H, each d, J = 6.0Hz), 1.25 ~ 2.20 (11H,
m), 2.49 (4H, m), 4.70 (1H, m), 6.72 (1H, d, J _HF = 6.0Hz), 7.20
(1H, d, J _HF = 9.0Hz). IR spectrum (KBr disk, cm ^-1 ): 1720, 1500, 1430, 137
5,1195.

Reference Example 7

[0075]

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2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (20.0 g, 91.1 mm
ol) and 3,4,5,6-tetrahydrophthalic anhydride (14.0 g, 92.0 mmol) in acetic acid (200 m
l) The solution was reacted for 5 hours while heating under reflux. After completion of the reaction, the mixture was cooled to room temperature, water (200 ml) was added, and the mixture was extracted with ethyl acetate (100 ml × 3 times). The organic layer is washed with an aqueous solution of sodium carbonate and water, and after drying,
The oily substance obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/5) to obtain
N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) -3,4,5,6-tetrahydrophthalimide white solid (26.2 g, 72.1 mmol)
1, yield 79.2%).

Melting point: 138.5-146.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ1.82 (4H,
m), 2.42 (4H, m), 3.93 (3H, s), 7.21 (1H, d, J _HF = 6.5Hz), 7.33
(1H, d, J _HF = 9.0Hz). IR spectrum (KBr disk, cm ^-1 ): 1765,1725,1508,150
0,1440,1430,1260,1195.

The above-obtained N- (2-fluoro-
4-chloro-5-methoxycarbonyloxyphenyl)
-3,4,5,6-tetrahydrophthalimide (11.
8 g, 33.4 mmol) of methanol (100 ml)
Potassium carbonate (4.6 g, 33.3 mmol) was added to the solution, and the mixture was stirred under reflux for 5 hours. After completion of the reaction, the mixture was poured into 1N hydrochloric acid (200 ml), and ethyl acetate (1 ml) was added.
00 ml × 3 times). The organic layer was washed with water, dried, and then the solvent was distilled off under reduced pressure to obtain a crude product (9.4 g). This was recrystallized from ether / hexane to give a white solid of N- (2-fluoro-4-chloro-5-hydroxyphenyl) -3,4,5,6-tetrahydrophthalimide (6.7 g, 22.
7 mmol, yield 67.8%).

Melting point: 145.5-156.4 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 1.80 (4H,
m), 2.40 (4H, m), 6.00 (1H, br s), 6.85 (1H, d, J _HF = 6.5Hz),
7.17 (1H, d, J _HF = 9.0 Hz). IR spectrum (KBr, cm ^-1 ): 3440, 1785, 1720, 1530, 143
0,1395,1185.

Reference Example 8

[0081]

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N- (2-fluoro-4-chloro-5-hydroxyphenyl) -3,4,5,6-tetrahydrophthalimide (2.0 g, 6.76 mmol) and potassium carbonate (0.60 g, 4.34 mmol) ) In acetonitrile (50 ml) solution was added to cyclopentyl bromide (1.
2 g, 8.1 mmol) and stirred under reflux for 2 hours. After the completion of the reaction, 1N hydrochloric acid (20
ml) and extracted with ethyl acetate (20 ml × 3 times).
The organic layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and ethanol (5 ml) was added to the obtained pale yellow oil to precipitate N- (2-fluoro-4-chloro-). 5-cyclopentyloxyphenyl)
-3,4,5,6-tetrahydrophthalimide white solid (0.75 g, 2.06 mmol, 30.5% yield)
Was isolated by filtration. Refer to Reference Example 4 for spectral data
As shown in FIG.

Reference Example 9

[0084]

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N- (2-fluoro-4-chloro-5-hydroxyphenyl) -3,4,5,6-tetrahydrophthalimide (2.0 g, 6.76 g) and potassium carbonate (0.60 g, 4.34 mmol) ) Was added to a solution of acetonitrile (50 ml), and cyclopentyl p-toluenesulfonate (1.90 g, 8.11 mmol) was added thereto.
Stirred at C for 2 hours. After completion of the reaction, 1N hydrochloric acid (20 ml) was added to the obtained reaction mixture, and ethyl acetate (20 ml × 3) was added.
Times). The organic layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and ethanol (5 ml) was added to the obtained pale yellow oil to precipitate N- (2-fluoro-4-chloro-). 5-cyclopentyloxyphenyl) -3,4,5,6-tetrahydrophthalimide white solid (0.77 g, 2.12 mmol,
(31.4% yield) was isolated by filtration. The spectrum data and the like are as shown in Reference Example 4.

Reference Example 10

[0087]

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Cyclopentanol (50.0 g, 0.58
mol) and p-toluenesulfonyl chloride (120
g, 0.629 mol) was dissolved in pyridine (200 ml), then poured into ice water (about 1 L), and thoroughly stirred.
The precipitated solid was filtered and dried to give cyclopentyl p-toluenesulfonate as a white solid (94.9).
g, 0.390 mol, yield: 68.1%).

Melting point: 30 ° C. or less ¹ H-NMR (CDCl ₃ , TMS, ppm): δ1.23 to 2.07 (8H,
m), 2.45 (3H, s), 4.98 (1H, m), 7.38 (2H, d, J = 9.0H
z), 7.85 (2H, d, J = 9.0Hz).

Reference Example 11

[0091]

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Cyclopentanol (10 g, 0.116 mol), p-toluenesulfonyl chloride (24.3 g, 0.128 mol) and ether (100 ml) were added to a 200 cc eggplant-shaped flask and dissolved. Then, powdered potassium hydroxide (32.5 g, 0.58 mol) was slowly added while cooling to 10 ° C. or lower in a water bath. After the addition, the mixture was further stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was poured into ice water (20 ml), and the organic layer and the aqueous layer were separated. The organic layer was dried and then concentrated under reduced pressure to obtain a pale yellow viscous liquid of cyclopentyl p-toluenesulfonate (22.0 g, yield: 81.8%).

Reference Example 12

[0094]

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In the same manner as in Reference Example 10, 3-methylcyclopentanol (5.0 g, 49.9 mmol)
And p-toluenesulfonyl chloride (10.0 g, 5
2.5 mmol) with pyridine (50 ml) to give 3-methylcyclopentyl p-toluenesulfonate (11.7 g, 46.2 mmol, yield 92.5%).
I got

¹ H-NMR (CDCl ₃ , TMS, ppm): δ 0.93 a
nd 1.00 (total 3H, each d, J = 6.0Hz), 1.20-2.30 (7H, m),
2.48 (3H, s), 4.97 (1H, m), 7.38 (1H, d, J = 8.0Hz), 7.85 (1H,
d, J = 8.0Hz).

The N-substituted phenyl-3,4,4 which can be produced by the methods exemplified in the above Examples and Reference Examples
Table 1 shows typical examples of 5,6-tetrahydrophthalimide derivatives.

Table 1 N-substituted phenyl-3,4,5,6
-Tetrahydrophthalimide derivative

[0099]

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[0100]

[Table 1]

[0101]

[Table 2]

The thus obtained N-substituted phenyl-3,
The 4,5,6-tetrahydrophthalimide derivative has excellent performance as a herbicide as described above.

When this compound is used as a herbicide, it can be used as it is, but in general, one or several adjuvants can be mixed and used as a herbicide. Usually, as an auxiliary, various carriers, extenders, solvents, surfactants, stabilizers, etc. are blended and formulated in a conventional manner, for example, into wettable powders, emulsions, powders, granules, flowables and the like. It is preferred to use.

Examples of the solvent which is one of auxiliary agents in a herbicide containing an N-substituted phenyl-3,4,5,6-tetrahydrophthalimide derivative as an active ingredient include, for example, water, alcohols, ketones, ethers, Suitable are aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, acid amides, esters, nitriles and the like, and one or a mixture of two or more of these are used.

Examples of the extender include clays such as kaolin and bentonite, talcs such as talc and pyrophyllite, diatomaceous earth,
Mineral powders such as oxides such as white carbon and vegetable powders such as soybean powder and CMC are used. Further, a surfactant may be used as a spreading agent, a dispersant, an emulsifier, or a penetrant. Examples of the surfactant include a nonionic surfactant, a cationic surfactant, an amphoteric surfactant, and the like. These surfactants are utilized as one kind or a mixture of two or more kinds depending on the use.

Preferable methods of using the herbicide containing the compound of the present invention as an active ingredient include soil treatment, water surface treatment, foliage treatment and the like. Can be mentioned.

Further, N-substituted phenyl-3,4,5,6
-A herbicide containing a tetrahydrophthalimide derivative as an active ingredient is used in combination with other active ingredients which do not inhibit the herbicidal activity of the present active ingredient, for example, other herbicides, insecticides, fungicides, plant growth regulators and the like. Mixed use or combined use is also possible.

Next, N-substituted phenyl-3,4,5,6
-The present invention will be described in more detail by way of formulation examples of herbicides containing a tetrahydrophthalimide derivative as an active ingredient and examples in which the herbicidal effects of the present herbicides have been studied. The parts are by weight.

Formulation Example 1 (Emulsion) 20 parts of Compound 10 shown in Table 1, 35 parts of xylene, 40 parts of cyclohexanone, and 5 parts of Solbol 900A (manufactured by Toho Chemical Co., Ltd.) were uniformly mixed to obtain an emulsion. Other compounds described in Table 1 were processed in the same manner as above to obtain emulsions.

Formulation Example 2 (Wettable powder) A mixture of 50 parts of compound 10 shown in Table 1, 25 parts of diatomaceous earth, 22 parts of clay, and 3 parts of Lunox R100C (manufactured by Toho Chemical) is uniformly mixed and pulverized to hydrate. Agent was obtained.

Formulation Example 3 (granules) 5 parts of compound 10 shown in Table 1, 35 parts of bentonite,
A mixture of 55 parts of talc and 5 parts of sodium ligninsulfonate was uniformly mixed and pulverized, kneaded by adding water, granulated by an extruder, dried and sized to obtain granules. Other compounds described in Table 1 were treated in the same manner as above,
Granules were obtained.

Test Example 1 (Effect on Paddy Field Weeds) A paddy field soil was filled in a 1 / 5,000 are Wagner pot, and the seeds of barnyard grass, oak, firefly, and 2-3
Leaves of rice seedlings (variety: Nipponbare) were sowed or transplanted and kept in a flooded state. After 5 days, the compounds shown in Table 1 as water-dispersible powders or emulsions according to the formulation examples were added at 5, 2.5, 1,
A predetermined amount of the diluent was subjected to a water surface treatment so as to be 0.5 g.
On the 20th day after the treatment, the herbicidal effect on the test plant and the phytotoxicity on the rice were investigated according to the following criteria.
The results in the table were obtained.

[0113]

[Table 3]

A commercially available Lonestar (trade name) was used as the control compound A, and the same preparation method and treatment method were used.
The herbicidal activity and the phytotoxicity to crops were investigated using the same criteria, and the results were shown.

[0115]

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[0116]

[Table 4]

Test Example 2 (Effect of Field Soil Treatment) A vat having an area of 16 × 11 cm ² and a depth of 7 cm was filled with field soil, and seeds of soybean, corn, soybean and corn were sown, and the seeds were sown. The top was covered with 1 cm of soil. The next day, the first wettable powder or emulsion was prepared according to the formulation example.
A predetermined amount of the diluting solution was evenly spread on the covering soil so that the compounds described in the table became 20, 10, and 5 grams per are. Twenty days after the treatment, the herbicidal effect on the test weeds and the phytotoxicity on soybean and corn were examined in the same manner as in Test Example 1. Table 3 shows the results.

[0118]

[Table 5]

Test Example 3 (Effects of Foliage Treatment) A vat having an area of 16 × 11 cm ² and a depth of 7 cm was filled with field soil, and seeds of Meechishiba, Shiroza, Dog millet and soybean were sown and grown 15 days later. A predetermined concentration of a wettable powder according to the formulation example or a diluted solution of the compound shown in Table 1 as an emulsion was sprayed onto the foliage of the plant at a water volume of 10 liters per are. Twenty days after the treatment, the herbicidal effect on the test weeds and the phytotoxicity on soybeans were examined in the same manner as in Test Example 1. Table 4 shows the results.

[0120]

[Table 6]

[0121]

By using the compound of the present invention, especially an isobutyl compound as an intermediate, N-substituted phenyl-3,
The 4,5,6-tetrahydrophthalimide derivative is easily produced. This derivative is useful as a herbicide because it has a high herbicidal effect on weeds at a low dose and has little phytotoxicity on main crops.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Emiko Ejiri 5-3-5 Wakamatsu, Sagamihara City, Kanagawa Prefecture House Azuma 202 (72) Inventor Kikuko Harasawa 4-17-11 Sainan, Sagamihara City, Kanagawa Prefecture 2nd Hiroshi Odai Building No. 302 (72) Inventor Yuichi Onchi 3-27-2 Tatsumidai Higashi, Ichihara City, Chiba Prefecture No. 504 (72) Inventor Sadayuki Ukai 4-15-12 Minamisurugadai, Fujieda City, Shizuoka Prefecture Rainbow Home B-202 ( 72) Inventor Shoin Nagato 3-13-13-106 Kahama, Adachi-ku, Tokyo Examiner Yoko Watanabe (56) References JP-A-63-310855 (JP, A) JP-A-63-183501 (JP, A) 4-210984 (JP, A) Tokuyo Sho 61-501032 (JP, A)

Claims (1)

(57) [Claims] [Claim 1] The following general formula: (Wherein, R ¹ represents an isobutyl group, X represents a halogen atom, and Y represents a hydrogen atom, a nitro group or an amino group).