JPH01226875A - Hydantoin and hydantoic acid derivative - Google Patents

Abstract

NEW MATERIAL:A hydantoin and hydantoic acid derivative expressed by formu las 1 and 2 (X<1> and X<2> are halogen; R<1> is lower alkyloxycarbonyl; R<2> and R<3> are H or lower alkyl; R<4> is lower alkyl). EXAMPLE:3-(2'-Fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl) -5-isopropylidene- hydantoin. USE:An intermediate for novel herbicides having both high selectivity and power ful herbicidal activity against various strongly noxious weeds. PREPARATION:An urea derivative expressed by formula 3 and an alpha- ketocarboxylic acid ester expressed by formula 4 are subjected to dehydrating condensation in the presence of a basic or acidic catalyst to provide a compound expressed by formula 2, which is then intramolecularly cyclized in the presence of a basic or acidic catalyst to afford the aimed compound expressed by formula 1.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to hydantoin derivatives, which are synthetic intermediates for the production of herbicides, and hydantoic acid derivatives, which are intermediates for the production thereof. More specifically, the present invention is based on the general formula R' [wherein, Xl and X8 independently represent a halogen atom, R1 represents a lower alkyloxycarbonyl group,
R′ and R3 independently represent a hydrogen atom or a lower alkyl group, and a hydantoin derivative represented by the formula [wherein XI, represents a lower alkyl group.

[Conventional technology]

Hydantoin derivatives have traditionally been known as important intermediates in amino acid synthesis, but it is difficult to synthesize hydantoin derivatives that have a substituent on the nitrogen at the 3-position and a disubstituted methylidene group at the 5-position. For this reason, there have been no reports so far, and -a hydantoic acid derivatives having a substituted vinyl group on the nitrogen atom as shown in formula (2) have not been known so far. Although hydantoic acid represented by is a type of so-called dehydroamino acid derivatives, there have been no reports on its synthesis, and no method for producing it by reacting urea with an α-ketoester is known.

Furthermore, although some hydantoin derivatives are known to have strong herbicidal activity, there have been no reports of herbicides containing hydantoin derivatives having alkylidene at the 5-position as an active ingredient.

[Problem that the invention seeks to solve]

The present invention is directed to novel hydantoin derivatives and hydantoin MP, which are important synthetic intermediates for the production of new tax herbicides that have both high selectivity and strong killing activity against various harmful weeds.
It is intended to provide a conductor.

As a result of extensive studies regarding the target hydantoin and hydantoic acid derivatives and their production method, the present inventors discovered that by reacting an aryl urea with an α-ketocarboxylic acid ester, an aryl group and a 1- The present inventors discovered that a new hydantoic acid derivative having an alkoxycarbonyl vinyl group can be easily produced, and that by treating this product with an acid or a base, a new hydantoin derivative having an alkylidene group at the 5-position can be easily produced, and thus completed the present invention. . These derivatives are good intermediates for producing herbicides with strong herbicidal activity.

[Means to solve the problem]

That is, the present invention provides a substituted phenyl group on the nitrogen at the 3-position as shown in the general formula [wherein, X', X", R', R-rich and R-co have the same meanings as above], A novel hydantoin m8 body having an alkylidene group at the
The present invention provides a novel hydantoic acid derivative characterized by having a substituted phenyl group on N and a substituted vinyl group on N', as shown in ], in which R3 and R4 have the same meanings as above.

The novel hydantoin derivatives of the present invention are obtained by hydrolyzing the lower alkoxycarbonyl group at the 5'-position of the phenyl ring to obtain a phenol derivative, and then introducing appropriate substituents on the oxygen at the 5'-position and the nitrogen at the 1-position. It can be converted into a hydantoin conductor with herbicidal activity. (See reference side below) This substance has very strong herbicidal activity,
For example, paddy field weeds such as Japanese barnyard grass, Japanese grasshopper, and Japanese grasshopper, etc., live here for a year! ! It also has a strong herbicidal effect on perennial weeds such as japonica japonica, fireweed, turmeric, and pine grass, and also selectively kills field weeds such as japonica japonica, japonica japonica, foxtail grass, whiteweed, knotweed, blueberry, purslane, etc. can do. (Refer to the test side below) According to the present invention, the novel hydantoin derivatives and hydantoin faM conductors shown in (1) and (2) above can be manufactured by the methods shown in Manufacturing Methods 1 and 2 below.

[Production method 1] [In the formula, Xl, X''+ R1, R1, R3 and R4 represent the same meanings as above] [Production method 2] [In the formula, R'
represents the same meaning as above.] [Production method 3] [In the formula, x', X", R'+ R", R" and R4 represent the same meaning as above.] General formula (3) which is a raw material compound
) The urea derivative represented by formula (5) can be produced by reacting an isocyanate derivative represented by formula (5) (see JP62-174065) with ammonia.

(In the formula, Xl, x-shape and R1 represent the same meanings as above.) In the description of the present invention, preferred examples and explanations of various definitions included within the scope of the present invention will be described in detail below. .

Methyl group, ethyl group, propyl group, butyl group, isobutyl group, t-butyl group, 5eC-butyl group, pentyl group,
3-Pentyl group, hexyl group, etc. can be removed. Therefore, examples of the "lower alkoxycarbonyl group" include methoxycarbonyl group, ethoxycarbonyl group, isobutyloxycarbonyl group, hexyloxycarbonyl group, and the like.

The "halogen atom" is preferably a fluorine atom, a chlorine atom or a bromine atom.

Next, the method for producing the hydantoin derivative represented by the above-mentioned -Kakuburu (1), which is the compound of the present invention, will be explained in detail below.

[Production method 1] The compound (1) of the present invention can be produced by intramolecular cyclization reaction by treating the urea derivative (2), which is the compound of the present invention, in the presence of a base or acid catalyst.

Suitable base catalysts include metal carbonate salts such as sodium carbonate and potassium carbonate, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium-1-butoxide, and alkali metal organic carboxylates such as sodium acetate and potassium acetate. Examples include salt. The amount of the base catalyst used is preferably 0.1 to 0.5 equivalents relative to the substrate.

Suitable acid catalysts include mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid; sulfonic acids such as p-toluenesulfonic acid, benzenesulfonic acid, and trifluoromethanesulfonic acid; and phosphorus oxychloride, phosphorus trichloride, and phosphorus pentachloride. Although phosphorus compounds and the like can be used, p-toluenesulfonic acid and benzenesulfonic acid, which are inexpensively available and easy to handle, are preferred acid catalysts in terms of good yields. The amount of acid catalyst to be used is preferably 0.1 to 0.5 equivalents based on the substrate.

Regardless of whether a base or M catalyst is used, the reaction is preferably carried out in an aqueous solvent.

Suitable aqueous solvents include aromatic solvents such as benzene and toluene, ketones such as acetone and methylenalketone, nitriles such as acetonitrile and isobutyronitrile, ethyl acetate, N, N-dimethylform, etc. '1
An organic solvent such as amide, dimethyl sulfoxide, or a mixed solvent thereof can be used. Hydantoin M8 (1) can also be obtained by performing this reaction in an aqueous hydrochloric acid solution while heating. The concentration of hydrochloric acid is 1
- Selected from 1ON.

Although the reaction temperature varies depending on the base, acid catalyst, or solvent used, it is not particularly limited, and the reaction is usually carried out under heating, and it is preferable to carry out the reaction at a temperature of 100 to 150° C. in terms of a good yield.

After completion of the reaction, the product can be obtained by conventional post-treatment, and if necessary, it can be purified by column chromatography, recrystallization, etc.

[Manufacturing method 2] Manufacturing method 2 is a method for manufacturing a hydantoic acid derivative by dehydration condensation of a urea derivative represented by -Sakaku (3) and an α-ketocarboxylic acid ester represented by general formula (4),
Either a base or an acid catalyst can be used as the catalyst. Suitable base catalysts include metal carbonate salts such as sodium carbonate and potassium carbonate, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium t-butoxide, and alkali metal organic carboxylates such as sodium acetate and potassium acetate. Examples include salt. The amount of base used is 0.05 to 0 relative to the substrate.
．． Sulfonic acids such as trifluoromethanesulfonic acid, phosphorus compounds such as phosphorus oxychloride, phosphorus trichloride, and phosphorus pentachloride, etc., which are preferably 5 equivalents, can be used; -+-Luenesulfonic acid and benzenesulfonic acid are preferred catalysts also in terms of good yield. The amount of catalyst M used is preferably 0.1 to 1.0 equivalents relative to the substrate.

Regardless of whether a base or acid catalyst is used as a catalyst, it is preferable to carry out the reaction in an organic solvent. Suitable organic solvents include aromatic solvents such as benzene, toluene, and xylene, dioxane, tetrahydrofuran, and dimethoxyethane. Ether solvents such as acetone, ketones such as methyl ethyl ketone, nitriles such as acetonitrile and isobutyronitrile, or ethyl acetate, N, N
- Organic solvents such as dimethylformamide and dimethyl sulfoxide or mixed solvents thereof can be used.

The reaction temperature varies depending on the base, acid catalyst, or solvent used, but is not particularly limited, and it is usually preferred to carry out the reaction at a temperature ranging from room temperature to 100°C in terms of good yield.
In addition, since this reaction is originally a dehydration condensation reaction, a solvent such as benzene or chloroform is used in the reaction using an acid catalyst, and the reaction is carried out at the reflux temperature of the solvent in a reaction apparatus equipped with a dehydration device such as Dean-Stark. It is most preferable to lie down.

After the reaction is completed, the ζ product can be obtained by conventional post-treatment, but if necessary, it can be purified by column chromatography, recrystallization, etc.

[Production method 3] The compound (2) of the present invention can be produced by an addition reaction between an isocyanate derivative (5) and a dehydroamino acid ester (6).

This reaction is carried out in a solvent. Suitable organic solvents include aromatic solvents such as benzene, toluene and xylene, ether solvents such as dioxane, tetrahydrofuran and dimethoxyethane, and organic solvents such as ethyl acetate, dimethylformamide and dimethyl sulfoxide.
The reaction can be carried out in any other solvent as long as it does not adversely affect the reaction.

The reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature to heating conditions, and when there is no exotherm, it is preferable to carry out the reaction under cooling.

Additionally, this reaction is usually carried out in the presence of a base.
The reaction can proceed more efficiently. As suitable bases, it is preferable to use, for example, tertiary amines such as triethylamine, tripropylamine, tributylamine, N-methylmorpholine, dimethylaniline, and aromatic amines such as pyridine, lutidine, and pyrimidine.

After completion of the reaction, the product can be obtained by conventional post-treatment, and if necessary, it can be purified by column chromatography, recrystallization, etc.

Next, the method for producing the urea derivative (3) as a raw material compound will be explained in detail below.

The urea derivative represented by the general formula (3) can be easily produced by adding ammonia to the isocyanate derivative represented by the general formula (5). (See reference side below) The reaction is carried out in a solvent. Suitable aqueous solvents include aromatic solvents such as benzene and toluene, ether solvents such as diethyl ether, dioxane, tetrahydrofuran, and dimethoxyethane, halogen solvents such as dichloromethane, chloroform, and carbon tetrachloride, methanol, ethanol, and the like. and organic solvents such as ethyl acetate and acetone. Furthermore, this reaction can also be carried out in an aqueous solution. At this time, in addition to ammonia, aqueous ammonia, ammonium chloride, etc. may be used as the ammonia source. The reaction is preferably carried out under cooling or at room temperature.

Formula -a of the present invention which can be synthesized in this way (
Typical hydantoin derivatives represented by 1) are shown in Table 1, and examples, reference examples, and test examples are given below. The present invention will now be further explained.

Example I II N-(2-fluoro-4-chloro-5
-methoxycarbonyloxyphenyl)-N'-(1'
-Ethoxycarbonyl-2'-methyl-1'-propenyl)urea (2.53 g, 6.5 mmol) and sodium acetate (140 mg) were added, and toluene (80 ml) was added.
) was added and reacted under reflux for 7 hours. After the reaction was completed, ethyl acetate (30 ml) was added thereto, and the mixture was washed with water (20 ml x 3 times). After drying the solution over anhydrous magnesium sulfate, it was subjected to γ4 condensation under reduced pressure to obtain a brown oil. A white solid of 3-(2'-fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (1.11 g) was precipitated by adding ether.
was collected by filtration. The mother liquor was further concentrated, an ether-hexane mixed solvent was added, and the precipitated solid (386 mir) was collected by filtration. The total yield was 67%.

Example 2 N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-N'-(1'-methoxycarbonyl-2'-methyl-1'-propenyl) urea (1,3
7 g, 3.5 mmol benzene (200 ml)
Sodium acetate (300 ml) was added to liquid i and heated under reflux for 20 hours. After the reaction was completed, the precipitated sodium acetate was filtered off, and the filtrate was concentrated under reduced pressure. Recrystallized from ether-pentane to give 3-(2'-fluoro-4'-chloro-5'-
Ethoxycarbonyloxyphenyl)-5-isopropylidenehydantoin as a pale yellow solid (1.24 g, yield 6
9%).

Example 3 II Me N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-N'-(1'-methoxycarbonyl-2'-methyl-1'-brohenyl)urea (4 g,
15.2 mmol) and methyl 2-oxo-3-methylpentanoate (3.4 g.

23.6 mmol) and p-toluenesulfonic acid (50
A solution of 0 w) in benzene (100 ml) was heated under reflux for 5 hours. After the completion of the 0 reaction, the precipitated solid was separated by filtration, the filtrate was washed with water, and then dried over anhydrous magnesium sulfate. After removing the desiccant by filtration, the solvent was distilled off, and then ether was added and the precipitated white solid was isolated by filtration. This thing is N-(2
-Fluoro-4-chloro-5-methoxyluponyloxyphenylene 7L/) -N'-(1'-methoxycarbonyl-2'-methyl-1'-butenyl)urea was confirmed by NMR spectrum.

Next, the obtained N,N'-disubstituted urea was added with p-1 toluenesulfonic acid (500 μl) as a catalyst, and toluene (1
00 ml) in the solvent and heated under reflux for 9 hours. After the precipitated solid was filtered off, the filtrate was washed with water.

3-
White crystals (2.05 g, yield 38%) of (2'-fluoro-4'-chloro-51-methoxycarbonyloxyphenyl)-5-(2"-butylidene)hydantoin were obtained.

Example 4 0mo5-methoxycarbonyloxyphenyl)-N'
-(1'-methoxycarbonyl-2'-methyl-1'-
Propenyl) urea (5.66g, 13.5mmol
) and toluene (90 ml) was added to dissolve it. Sodium acetate (114μ) was added and heated under reflux for 3 hours. The reaction mixture was washed with water (50ml x 3 times) and dried over anhydrous magnesium sulfate to give 3-(2'-fluoro-4'-bromo-5'-methoxycarbonyl). oxyphenyl)-5-
White crystals of isopropylidenehydantoin (1.50g
) was obtained. By concentrating liquid d and adding ether, a white solid (<1.94 g) was further precipitated and collected by filtration. The total yield was 68%.

Example 5 N-(2,4-dichloro-5-methoxycarbonyloxyphenyl)-N'-(1'-methoxycarbonyl-2'-methyl-1'-propenyl)urea (6,76 g, 17.3 mmol), benzene (60 ml) was added, and then sodium acetate (149 mmol) was added.
(2) was added and heated under reflux for 7 hours. After completion of the reaction, the reaction solution was cooled and the precipitated solid was removed. Add the filtrate to water (50ml
After washing and drying (3 times), the solvent was distilled off under reduced pressure to obtain a brown oil. White crystals of 3-(2',4'-dichloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (3.97 g, yield 64%) were precipitated by adding chloroform (100 ml).
I got it.

Example 6 U N-(2-fluoro-4-chloro-5
-methoxycarbonyloxyphenyl)-N'-(1'
-methoxycarbonyl-3-methyl-1'-butenyl)
Urea (7.77 g, 20.0 mmol) was added, toluene (200 ml) was added, then sodium acetate (800 μl) was added, and the mixture was heated under reflux for 5 hours. After the reaction was complete,
The reaction solution was cooled and the precipitated solid was removed. The filtrate was washed with IN hydrochloric acid, dried, and the solvent was distilled off under reduced pressure to obtain a pale brown oil. This product was purified by silica gel column chromatography to obtain white crystals of 3-(2'-fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-isobutylidenehydantoin (5.76 g, yield: 84%).

Example 7 N-(2-fluoro-4-chloro-5
-methoxycarbonyloxyphenyl)-N'(1'-
Ethoxycarbonyl-2'-methyl-1'-propenyl)urea (7.77 g, 20.0 mmol) and 6N hydrochloric acid (200 ml) were added and stirred for 5 hours under heating under reflux. After the reaction, the solution was cooled and precipitated. White crystals of 3-<2'-fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (6.31 g, 92% yield) were isolated by filtration.

Example 8 N-(2,4-dichloro-5-methoxycarbonyloxyphenyl)-N'-(1'-ethoxycarbonyl-2'-methyl-1'-butenyl)urea (
8.10 g, 20.0 mmol) and p-
) Add luenesulfonic acid (700μ) and add toluene (3
00ml) 0 which was reacted in a solvent under heating reflux for 5 hours
After the reaction was completed, the solution was washed with water, dried, and the solvent was removed under reduced pressure. The obtained pale yellow oil was purified by silica gel column chromatography to obtain 3-(2'
, 4'-dichloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (6.25 g, yield 87%) was obtained.

Example 9 Methoxycarbonyloxyphenyl isocyanate) (
Add 2.45g, 10mmol I) and add benzene (100
ml) and then dehydroparithyl ester (1
, 41 g + l Ommol l) and stirred at room temperature.
After 0 hours of reaction, the precipitated solid was removed and the solution was added with saturated ammonium chloride water. Add 8 liquids and add ether (100ml x 3
extracted). The organic layer was washed with water (50 ml x J times) and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure. A white solid (3.45 g) of N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-N"(1'-ethoxycarbonyl-2'-methyl-1'-propenyl)urea was precipitated.
) was collected by filtration. The yield was 92%.

Example 10 2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl isocyanate (1,2
8g, 4.41mmo +) and benzene (100m
dehydrovaline methyl ester (6
After reacting at room temperature for 10 hours, the precipitated solid was removed, a saturated aqueous ammonium chloride solution was added to the solution, and the mixture was extracted with ether (100 ml Xa times).

The organic layer was washed with water (50ml××) and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure. The precipitated N-(2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl)-N'-(
A white solid (483 cm) of 1'-methoxycarbonyl-2'-methyl-11-propenyl)urea was collected by filtration. Ether was added to the filtrate and the mixture was cooled to precipitate a white solid (385 cm), which was the desired product, and was obtained by filtration.

The total yield was 47%.

Example 11 2.4-dichloro-5-methoxycarbonyloxyphenylisocyanate (1,31 g).

Put 5 mmol) into an eggplant-shaped flask and add benzene (l
OQm i) and then dehydrovaline methyl ester (0.65 g, 5 mmol I) and stirred at room temperature for 7 hours.
I reacted in time. A small amount of precipitated solid was removed and the solution was washed with aqueous ammonium chloride solution (500 ml x 3) and water (cIQml x 3). After drying, the solvent was distilled off from the solution under reduced pressure to obtain a brown oil (1.35 g). An ethyl acetate-hexane mixed solution was added to this, and the precipitated N-(2,4-dichloro-5-methquinecarbonyloxyphenyl)-N'-(1'-methoxycarbonyl-
2'-Methyl-1'-propenyl) urea white solid (1
, 31 g, yield 58%) was collected by filtration.

Example 12 Hensen's (loOm
l)? In liquid a, the catalyst species p-)luenesulfonic acid (60g
g, 0.35 mmol]) to obtain an oil. A pale yellow solid was obtained by recrystallization from ether-pentane. By recrystallizing this product from an ether-pentane mixed solvent, N-(2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl)-N'-
(1'-Ethoxycarbonyl-2'-methyl-1'-propenyl)urea (11.0 g, yield 77%) was obtained.

Example 13 By the same operation as in Example 12, 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea (1
00m, 0.38mmol) and N-(N'
-(2-Fluoro-4-chloro-5-methoxycarbonyloxyphenyl)carbamoyl)dehydrovaline methyl ester (71■.

A yield of 84% was obtained.

Example 14 By the same operation as in Example 12, 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea (2
N-(N'-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)carbamoyl)dehydrovaline methyl Esther (225■.

A yield of 61%) was obtained.

Example 15 2-Fluoro-4-bromo-5-methoxycarbonyloxyphenylurea (15.2 g, 50 mmol) was added to a 200 ml eggplant flask fitted with a Dean-Stark apparatus.
l), ethyl 2-oxoisovalerate (12 ml) and toluene (140 ml) were added as a solvent, and then sodium ethoxide (169 ml) was added and heated under reflux for 20 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution (100 ml) was added to the reaction solution. ) to make it acidic and ether (100 m
lxa times). The ia layer was washed with water and then dried over anhydrous magnesium sulfate. After filtering off the desiccant, the bay liquid was concentrated under reduced pressure. The precipitated pale yellow solid (4.6 g) was isolated by filtration. Ether was added to the filtrate, and the precipitated pale yellow solid was filtered off.

All of these products are the target N-(2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl)-N'-(1'-ethoxy-carbonyl-21-methyl-1'-propenyl)urea. 'H-NM
R is more certain than t=.

The combined rate was 28%.

By the same operation as in Project Example 15, 2-fluoro-4-bromo-5-methoxycarbonyloxyphenylurea (1
84m, 0.60mmol) and methyl 2-oxoisovalerate (93.7w, 7.2mmol) to N-(N'-(2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl)carbamoyl) Dehydrovaline methyl ester (163■.

A yield of 65% was obtained.

Example 17 2,4-dichloro-5-methoxycarbonyloxyphenylurea (10.3 g, 37 mmol) was added to a 200 ml eggplant flask fitted with a Dean Stark apparatus.
- Ethyl oxoisovalerate (9,0 g) and benzene (150 ml) as solvent were added, then p
-Toluenesulfonic acid (644 ml) was added and heated under reflux for 7 hours. After the reaction, the organic layer was washed with water and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the solution was concentrated under reduced pressure to obtain a brown oil (17.4 g). N-(2
,4-dichloro-5-methoxycarbonyloxyphenyl) -N'-(1'-ethoxycarbonyl-2'
-Methyl-11-propenyl)urea (7.0 g, yield 4
7%) of white powder was obtained.

Reference Example 1 2-Fluoro-4-chloro-5-methoxycarbonyloxyphenyl isocyanate (12.3 g.

Ammonia gas was introduced into a solution of 50 mmol) in benzene (100 ml) with vigorous stirring under water cooling. 30
After a few minutes, the white solid precipitated was filtered, thoroughly washed with benzene, and dried. This product is the desired 2-fluoro-4-chloro-5-methquine carbonyloxyphenylurea (1
0.3 g, yield 78%) from NMR spectra etc. did.

'H-NMR (DMSO-d, TMS, ppm) =
63.87 (3H,S), 5.81 (2H
, brs), 7.12 (IH, d, J) I
F=l 0H2).

8.28 (IH, d, J,, = 7.2Hz>.

8.48 (IH, br s).

Reference Example 2 2-Fluoro-4-chloro-5-methoxycarbonyloxyphenyl isocyanate (16.7 g.

64 mmol) of benzene (300 ml)? Ammonia gas was introduced into the liquid No. 8 while stirring vigorously under water cooling. A white solid was immediately observed to precipitate.

After 30 minutes, the precipitated solid was collected by filtration, thoroughly washed with benzene, and dried. This product is the desired 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea (1
4.2 g, yield 80%).

'H-NMR (CDCl2-CD!OD, TMS.

ppm): δ 8.07 (IH, d, J=7.2H
z), 7.10 (IH, d, J-10, 2Hz).

4.30 (2H, q, J=7.2Hz), 1.37
(3H, t, J-7, 2Hz).

Reference Example 3 2-Fluoro-4-bromo-5-methoxycarbonyloxyphenylurea was obtained from 2-fluoro-4-bromo-5-methoxycarbonyloxyphenylisocyanate (47.7 g, 164 mmol) in the same manner as in Reference Example 1. (37.7 g, yield 75%) was obtained.

'H-NMR (CDC1, -CD30D, TMS.

ppm): δ 3.83 (IHS), 7.28 (IH
, d, J, F”l0H2), 7.99 (I H, q, J
MF=7.2H2).

Reference Example 4 2.4-dichloro-5-methoxyluponyloxyphenylisocyanate (5.04 g).

Ammonia gas was introduced into a solution of 19.2 mmol) in benzene (120 ml) while stirring vigorously under cooling. A white solid precipitated for 30 minutes was filtered and thoroughly washed with benzene. This product is the desired 2,4-dichloro-5
-Methoxycarbonyloxyphenylurea (4.68g
, yield 88%) was confirmed from 'H-NMR spectrum.

' HN M R (D M S O-d h, T M
S, I) pm): 63.88 (3H,s
), 6.35 (2H, br).

7.45 (IHs), 8.20 (IH,br)
.

8.32 (IHs).

Reference Example 5 3- synthesized according to the method shown in Example 1 or 7
(2'-Fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (8.1 g, 22.7 mmol) was placed in an eggplant-shaped flask, and L)MF (200 ml) was added. Dissolved. Potassium carbonate (1 (i, 9 g) and methyl iosite (
After the reaction was completed, the mixture was acidified using a saturated ammonium chloride aqueous solution and extracted with ether (100 ml××). The organic layer was diluted with water (5
0 ml x 3 times) and dried using anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a brown oil (6.5 g, 78% yield). This product was confirmed by spectroscopy to be 1-methyl-3-(2'-fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin.

'HNMR (CDCl s, TMS, ppm
) :δ 2.1? (3H,s), 2.3
4 (3H.

s), 3.42 (3H1s), 3.85 (3H
.

s) 7.27 (IH, d, Jar-2, 9Hz).

7.40 (IH, d, J,,”4.5Hz).

Next, l-methyl-3-(2'-fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-
Isopropylidenehydantoin (6.5g, 17.6m
mol) in an eggplant-shaped flask, methanol (60 mol)
ml) was added and dissolved. Potassium carbonate (2.5g)
was added and stirred at 40°C for 4 hours. After completion of the reaction, saturated ammonium chloride aqueous solution was added to make it acidic, and ether (30
ml x 3 times). The organic layer was diluted with water (LOMLX
After washing with 3 times), it was dried with anhydrous magnesium sulfate.

After removing the drying agent, the solution was concentrated under reduced pressure to obtain a brown oil. This was purified by single M silica gel column chromatography (ethyl acetate). From the spectrum, this one is 1
-Methyl-3-(2'-fluoro-4' to chloro-5'
-hydroxyphenyl)-5-isopropylidenehydantoin.

This 1-methyl-3-(2'-fluoro-4'-chloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (900 μ, 3.0 mmol) was placed in an eggplant-shaped flask, and acetonitrile (30 ml) was added. and dissolved. Potassium carbonate (1.02 g) and propargyl bromide (2.6 ml) were added and stirred at 40° C. for 4 hours. After completion of the reaction, the mixture was acidified using a saturated aqueous ammonium chloride solution and extracted with ether (loml x J times).

Organic 10 was washed with water (5 ml x 3) and dried over anhydrous magnesium sulfate. The desiccant was removed, the mixture was concentrated under reduced pressure F, and the precipitated white solid was collected by filtration, and further recrystallized from ethanol to obtain white crystals (264 cm, yield 26%). The spectrum of this product revealed that 1-methyl-3-(2'-fluoro-4'-chloro-5'-propargyloxyphenyl)-5-isopropylidenehydantoin [Compound A
] was confirmed.

Melting point: 152-153°C Elemental analysis (1! (calculated value): C, 56,54 (57,0
7); H, 4, 11 (4°19); N.

8.20 (8,32)%.

'H-NMR (CDCI, TMS, δ ppm)
:2.17 (3H,s), 2.33 (
3H,s).

2.47 (IH, t, J-2,4Hz),
3.40 (3H, s), 4.66 (2H, d,
J=2.4Hz), 6.90 (IH,d,
JMF-6,0H2).

7.18 (I H, d, JIIF-8, 8)+
2).

[R(KBr, cs-'): 1770. 17
30° Reference Example 6 e 3-(2'-Fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-(2-butylidene)hydantoin (1,
Put 02g, 3.0mmo +1 into an eggplant-shaped flask,
Methanol (40 ml) was added to dissolve. Potassium carbonate (230 μl) was added and reacted at room temperature for 15 hours. After the reaction was completed, it was made acidic using IN hydrochloric acid, and ether (10 μl) was added.
Extracted with lx30'). Add the organic layer to water (5ml x 30)
and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure to obtain a colorless G-light oil (893w).

NMR spectra etc. show that this product is almost pure 3-(2'-fluoro-4'-chloro-5'-hydroxophenyl)-5-(2-butylidene)hydantoin. Approved.

Then 3-(2'-fluoro-4'-chloro-5'-hydroxyphenyl)-5-((2-butylidene)hydantoin (170 μ, 0.57 mmol) in N,N-dimenalformamide (20 ml)? Potassium carbonate (
170 ml) and methyl iosite (500 μl) were added, and the mixture was stirred at room temperature for 2 hours. 3N hydrochloric acid was added, and ether (10 ml) was added.
Extracted with lx3 times). The organic layer was washed with water (5 ml x 2) and dried over anhydrous magnesium sulfate.

The solution was condensed with 'tM under reduced pressure, and the resulting pale yellow oil was isolated and purified by silica gel column chromatography to obtain l-methyl-3-(2'-fluoro-41-
Colorless oil of chloro-5'-methoxyphenyl)-5-(2-butylidene)hydantoin [Compound B] (180
(2), yield 97%) was obtained.

Elemental analysis 4a (calculated value): C, 55,38 (55,1
4); H, 4,73 (4,94); N.

8.42 (8,57)%.

'H-NMR (CDCIj, TMS, δpp resistance:
1.10and1.19 (total 3H.

each t, J=8. IH2), 2.15and2
．． 31 (total 3H, each), 2.
48and2.80 (tota12H, each
q, J=8.1Hz).

3.42 (3H, s), 3.84 (3H, 3)
.

6.83 (IH, d, J,, -6,3H2).

7.26 (I H, d, JllF= 9.OHZ)
.

IR (KBr, cm-'): 1765. 1710° Reference Example 7 3-(2' synthesized according to Example 4) was placed in an eggplant-shaped flask.
-Fluoro-4'-bromo-5'-methoxycarbonyloxyph-nyl)-5-isopropylidenehydantoin (1.5 g, 3.7 mmol) was added to DMF (70
ml) was added and dissolved. Potassium carbonate (2.51g
) and methyl iossite (3.4 ml) were added and stirred at 50° C. for 2 hours. After the reaction was completed, the mixture was acidified using 1N hydrochloric acid and extracted with ether (40 ml x 3 times). The organic layer was washed with water (20 ml x 3) and dried using anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a colorless i3 bright mass (1,271, 81% yield).

From the spectrum, this product is 1-methyl-3-(2'-
The product was confirmed to be fluoro-4'-bromo-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin.

'H-NMR (CDCI, TMS, δ ppm+
) :62.17 (3)(,s), 2.34
(3H, s).

3.44 (3H,s), 3.83 (3H,s)
.

6.78 (IH, d, JNF”9.0H2).

Next, 1-methyl-3-(2'-fluoro-4'-bromo-5'-methquinecarbonyloxyphenyl)-5-isopropylidenehydantoin (1,0
3 g, 2.57 mmol) and methanol (10
ml) was added and dissolved. Add potassium carbonate (50
(2) was added and stirred at 50° C. for 2 hours. After the reaction was completed, the mixture was acidified using 1N hydrochloric acid and extracted with ether (40ml x 3 times). The organic layer was washed with water (20 ml x 3) and dried using anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a yellow oil (1.04g).
) was obtained. This was isolated and purified by silica gel column chromatography (ethyl acetate/hexane-1/l) to obtain an oil (430 ml). This product was confirmed by spectroscopy to be substantially pure 1-methyl-3-(2'-fluoro-4'-bromo-5'-hydroxyphenyl) to 5-isopropylidenehydantoin. The product was further purified by gel column chromatography (ethyl acetate/chloroform-1/2) to obtain a colorless transparent oil (319Q1, yield 36%).

Then 1-methyl-3-(2'-fluoro-4'-bromo-5'-hydroxyphenyl)-5-isopropylidenehydantoin (101).

0.34 mmol) into an eggplant-shaped flask, and
N-dimethylformamide (10 ml) was added and dissolved. Potassium carbonate (200 μ) and propargyl bromide (350 μ) were added and stirred at 40°C for 5 hours.
lx3 times). The organic layer was washed with water (2 ml x 3) and dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a clear colorless oil.

Add ethanol and cool to -78°C to precipitate a white solid (
Go■, yield 52%) was collected by filtration. The spectrum confirmed that this compound was 1-methyl-3-(2'-fluoro-4'-bromo-5'-propargyloxyphenyl)-5-isopropylidenehydantoin [Compound C].

Melting point: 142-144°C Elemental analysis value (calculated): C, 50,12 (50,41)
:H, 3,63(3,70);N.

7.33 (7,35)%.

'H-NMR (CDC1, TMS, δppm)
:2.1? (3H,s), 2.35 (3H,s
).

2.57 (IH, t, J=2.11(z), 3.44
(3H, s), 4.71 (2H, d, J-2, 1H
z), 6.99 (IH, d, J,, -6,3Hz),
7.44 (IH, d, J,,”9.0)(z).

IR (KBr, 3-'): 1770, 1730° Reference Example 8 3-(2',4'-dichloro-5'-methoxycarbonyloxyphenyl synthesized according to the method shown in Example 5 or 8) in an eggplant-shaped flask. )-5-isopropylidenehydantoin (2.3 g.

6.4 mmol) and dissolved in methanol (40 ml). Add potassium carbonate (500μ) to this and 60℃
After stirring for 1 hour, the reaction solution was made acidic using IN hydrochloric acid and extracted with ether (20 ml x 3 times). The organic layer was washed with water (10 ml x 3 times) and then dried over anhydrous magnesium sulfate.

After removing the drying agent, the solution was concentrated under reduced pressure to obtain a pale yellow oil (1.93 g). Ether was added thereto to precipitate a white solid (1.02 g) of 3-(2',4'-dichloro-5'-hydroxyphenyl; 5-isopropylidenehydantoin), which was collected by filtration.

Further, the mother liquor was concentrated and ether was added to form a white solid (0,9
The zero reaction obtained g) was quantitative.

Next, 3-(2',4'-dichloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (97
0 w, 3.22 mmo I) of dimethylformamide (
Potassium carbonate (702 ml) and propargyl bromide (2.9 ml) were added to the 4 liquid (40 ml) at 50°C for 4 hours.
After the reaction was completed by further stirring at 80° C. for 8 hours, the mixture was made acidic by adding IN hydrochloric acid and extracted with Chill (20 ml x 3 times). The organic layer was washed with water and then dried over anhydrous magnesium sulfate.

The drying agent was filtered off and the solution was concentrated under reduced pressure to give a pale yellow oil (<1.95 g). After adding ether and cooling, the precipitated white isomer (193■) was increased by 4.

From the 'H-NMR spectrum, etc., this product has a phenyl ring of 5
3-(2',
4'-dichloro-5'-propargyloxyphenyl)
It was confirmed that it was -5-isopropylidenehydantoin. Furthermore, by concentrating the filtrate and recrystallizing it from chloroform-hexane, a propargyl group was also introduced onto the 1-position N of the hydantoin ring.
'.

4'-dichloro-5'-propargyloxyphenyl)
-White crystals of 5-isopropylidenehydantoin (69
4■, yield 57%) was obtained.

Next, 3-(2',4'-dichloro-5'-propargyloxyphenyl)-5-isopropylidenehydantoin (150 mg, 0.44 mmol) was placed in an eggplant-shaped flask, and N,N-dimethylformamide (20 ml) was added to the flask.
) was added and dissolved. Potassium carbonate (300 μ) and methyl iosite (630 μ) were added and stirred at 60° C. for 14 hours. After the reaction was completed, the mixture was acidified using IN hydrochloric acid and extracted with ether (10 ml x 3). The organic layer was dissolved in water (5 ml).
x 3 times) and dried over anhydrous magnesium sulfate.

The desiccant was removed and the solution was reduced to 44 mL to give a pale yellow oil. After adding ethanol and cooling to -78°C, a white solid (124 cm) precipitated.

(yield: 80%) was collected by filtration. The spectrum confirmed that this product was 1-methyl-3-(2',4'-dichloro-5'-propargyloxyphenyl)-5-isopropylidenehydantoin [Compound D].

Melting point 7 114-117℃ Elemental analysis (* (calculated value): C, 54, 27 (54
,41);H,4,02(4,00);N.

7.05 (7,93)%.

'H-NMR (CDC13, TMS, δ ppm
) :2.16 (3H,s), 2.34
(3H, s).

2.58 (IH, t, J=1.8Hz), 3
．． 43 (3H, s), 4.72 (2H, d,
J=1.8Hz), 6.99 (IH,s),
7.52 (IH.

s).

IR (KBr, am-'): 17?0. 17
20° Herbicidal Activity Test Example New hydantoin derivatives (compounds A to D) synthesized by the reactions illustrated in Reference Examples 5 to 8 were formulated according to a prescribed method, and their herbicidal activity tests were conducted. The results are shown below.

Formulation Example 1 (Emulsion) 20 parts of the compound of the present invention, 35 parts of xylene, 40 parts of cyclohexanone, and 5 parts of Tsurpol 900A (manufactured by Toho Chemical Co., Ltd.) are uniformly mixed to form an emulsion.

Emulsion Example 2 (Wettable powder) 50 parts of the compound of the present invention, ±25 parts of diatom, 22 parts of clay,
A mixture of 3 parts of Runonox R100C (manufactured by Toho Chemical Co., Ltd.) was evenly mixed and ground to obtain a wettable powder.

Formulation Example 3 (granules) 5 parts of the compound of the present invention, 35 parts of bentonite, 55 parts of talc
After uniformly mixing and pulverizing a mixture of 5 parts of sodium lignosulfonate and 5 parts of sodium ligninsulfonate, water is added and kneaded, the mixture is made into granules using an extrusion granulator, and then dried and sized to form granules.

Test example l (Efficacy on paddy field weeds) s, ooo
Two soils were filled in a 1/2-area Wagner pot, and seeds of Japanese barnyard grass, Konagi, and Nimemigi were sown or transplanted at the 3- to 4-leaf stage (variety Nikka) and kept in a fully watered state. 5 days 1 of the herbicide of the present invention as granules according to Formulation Example 3]
A predetermined amount of 20.10.5 g of the ingredient was applied to the water surface.30 days after treatment, the herbicidal effect on test plants and on rice were investigated using the following criteria. 4° result was obtained.

Judgment criteria: Rice/ha Grass killing rate: Remaining grass percentage (%) 1 clear)
0; 81-100 L for wheat: st-80 Effect 2: 41-60 Yo 3: 21-40 Koni 4 = 6-20 East damage 5: 0-5 &'s medicine damage: Growth rate -: No +: Slight damage ++: Small +++: Medium damage +++++ L Severe damage ×: Death test Example 2 (Efficacy against weeds) Fill a Wagner pot of 1/5,000 are with field soil and use it as a weed. As crops, soybean seeds were inserted, and 11 soil was covered on top of them. The next day, the diluted solution of the wettable powder shown in Formulation Example 2 was uniformly sprayed on the soil covering so that the active ingredient was 20.10.5 g per area, and 20 days after treatment, the herbicidal effect and herbicidal damage were confirmed. The results were investigated in the same manner as in Test Example 1. The results are shown in Table 5.

Written amendment filed in September 1989 by the Commissioner of the Japan Patent Office Yoshi 1) Takeshi Moon 1, Indication of the case, Patent Application No. 52590 filed in 1988 2, Name of the invention hydantoin and hydantoic acid derivatives 3, Person making the amendment Case Relationship with Patent Applicant: Address: 1-4-5-4 Marunouchi, Chiyoda-ku, Tokyo, Subject of Amendment 5, Contents of Amendment + 11 Line 4, Page 1, Page 1 of the Specification of the Application From page 2, line 7, "Claim J is amended as follows.

``2. Claims fil-satsu [In the formula, xl and x8 independently represent a halogen atom, R+ represents a lower alkyloxycarbonyl group,
A hydantoin derivative represented by ], wherein R1 and R3 independently represent a hydrogen atom or a lower alkyl group.

(2)-Sakatsu [In the formula, xl and X'' independently represent a halogen atom, R1 represents a lower alkyloxycarbonyl group,
R1 and R3 independently represent a hydrogen atom or a lower alkyl group, and R4 represents a lower alkyl group.''(2) No.
Correct the line r fll J to ' f2) J.

(3) Correct r (21J to ' (11J) on page 8, line 6.

(4) Page 10, lines 1 to 2 (3)”, Correct to.

(Correct ``ethoxy'' to ``methoxy'' in line 8 of page 21 of 9).

(6) rN-(2-fluoro...propenyl) urea J on page 24, lines 5 to 8 of the same page to "2-fluoro-4-chloro-5-methoxycarbonyloxyphenylurea j" correct.

(7) Correct "噸" in line 4 of page 36 to r g J.

(8) Correct Me J in the second line of page 40 to Me J.

that's all

Claims (1)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) [In the formula, X^1 and X^2 each independently represent a halogen atom. R^1 represents a lower alkyloxycarbonyl group. R^2 and R^3 each independently represent a hydrogen atom or a lower alkyl group. A hydantoin derivative represented by ]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (2) [In the formula, X^1 and X^2 each independently represent a halogen atom. R^1 represents a lower alkyloxycarbonyl group. R^2 and R^3 each independently represent a hydrogen atom or a lower alkyl group. ] A hydantoic acid derivative.