JPS63183567A - Hydantoin derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (X and Y are halogen; R<1> is H, alkyl, cycloalkyl, alkenyl or alkynyl; R<2> is H, alkyl, alkenyl or alkynyl; R<3> and R<4> are H or lower alkyl). EXAMPLE:1-Methyl-3-(2'-fluoro-4'-chloro-5'-methoxyphenyl)-5-isopropyli denehyda ntoin. USE:A herbicide exhibiting especially excellent herbicidal effect by the application before sprouting or in the young sprout stage of weeds. PREPARATION:The compound of formula I can be produced e.g. by reacting a compound of formula II successively with compounds of formula R<1>Z and formula R<2>Z (Z is eliminable group) in the presence of a base preferably in an organic solvent. The starting compound of formula II is obtained by treating a compound of formula III (R<5> is lower alkyl or aralkyl) in the presence of a base, thereby removing carbonate group.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to novel hydantoin derivatives.

More specifically, it relates to hydantoin derivatives having an alkylidene substituent at the 5-position. The 728 bodies are useful as herbicides. , [Conventional technology] ・
- It is known that among hydantoin derivatives, there are compounds that exhibit biological and physical activities such as herbicidal and fungicidal activities. For example, □ has herbicidal activity. -80695.51・, +363
3.2, Publication 6, JP-A-57-58672, 57-1
9,7°268.5B-219167,6,1-697
Hydantoin derivatives described in Japanese Patent No. 63 are known.

[Problems to be solved by the invention] - However, conventional hydantoin derivatives with herbicidal and herbicidal activity have insufficient herbicidal activity against harmful weeds, and there is a need for new compounds that can kill these weeds at low doses. Ta.

[Means for solving problems]

As a result of studies on various hydantoin derivatives, the present inventors found that the general formula: R2 represents a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group
and R4 independently represent a hydrogen atom or a lower alkyl group,] A novel hydantoin derivative having an alkylidene group at the 5-position exhibits strong herbicidal activity at a low dose and is a fully practical herbicide. The present invention was completed based on the discovery that this can be achieved.

A novel hydantoin derivative, which is the active ingredient of the present invention represented by general formula (1), can be produced, for example, by the method shown below.

That is, general formula (A) [wherein X, Y, R' and R4 represent the same meanings as above. This one has the general formula (
In the compound group represented by 1), R1 and Rz are both hydrogen atoms. The hydantoin derivative represented by
and R2 have the same meanings as above. Z is a leaving group. ] by reacting with the general formulas (B), (C) and (D) [in the formula, X,
A hydantoin derivative represented by Y, R'=, R'', R3 and R4 have the same meanings as above can be easily produced.

Preferably, the reaction is carried out in an organic solvent. Examples of organic solvents include tetrahydrofuran, diethyl ether, dimethoxyethane, dimethylformamide, dimethyl sulfoxide, acetonitrile, propionitrile, acetone,
Examples include solvents such as methyl ethyl ketone, benzene, and toluene.

The reaction is carried out in the presence of a base, such as n-butyllithium, 5ec-butyllithium, methyllithium, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium acetate, potassium acetate, Sodium hydroxide, potassium hydroxide, calcium hydroxide, etc. can be used.

The reaction temperature varies depending on the base and solvent used, but -
The temperature is selected from the range of 78°C to 150°C.

In this reaction, the product can be isolated as crystals by ordinary post-treatment after completion of the reaction, but if necessary, it can be purified by silica gel column chromatography or recrystallization.

Further, the hydantoin derivative represented by the general formula (A) can be produced by the method shown below.

That is, general formula (V) [wherein, X, Y, R3 and R
4 represents the same meaning as above. A hydantoin derivative represented by general formula (A) can be obtained by removing the carbonate group from the hydantoin derivative represented by [Rs represents a lower alkyl group or an aralkyl group] in the presence of a base.

Furthermore, a hydantoin derivative represented by general formula (C) can be produced by a similar production method.

That is, a hydantoin derivative represented by general formula (4) is added to a compound R''Z represented by general formula (3) in the presence of a base.
(In the formula, R2 and Z represent the same meanings as above,
] to alkylate the nitrogen atom to form a hydantoin derivative (5) [wherein, By removing , a hydantoin derivative represented by general formula (C) can be produced.

In the novel hydantoin derivative represented by the general formula (1) of the present invention that can be produced in this way,
Examples of halogen atoms represented by and Y include chlorine,
Mention may be made of bromine, fluorine and iodine. Examples of the alkyl group represented by R' include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s
e C-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl i, tert-pentyl group, hexyl group, isohexyl group, l-methylpentyl group, 2-methylpentyl group, octyl group, 1-methyloctyl group Examples of the cycloalkyl group include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, and a cyclododecyl group. Examples of alkenyl groups include allyl group, methallyl group, crotyl group, l-methyl□ allyl group, 1,1-dimethylallyl group, prenyl group, 3-methyl-3-butenyl group, 3-pentenyl group,
-Methyl-3-butenyl group, neryl group, geranyl group, 1
-Chloroallyl group, 2-chloroallyl group, 3-chloroallyl group, 3-bromoallyl group, 2-bromo-2-butenyl group, etc. as an alkynyl group include propargyl group, 1
-Methylpropargyl group, 1,1-dimethylpropargyl group, 1-ethylpropargyl group, 2-7'' thinyl group,
1-methyl-2-butynyl group, 3-pentynyl group, 3-
Examples include butynyl group and 2-pentynyl group.

Examples of the lower alkyl group represented by R3 and R4 include methyl group, ethyl group, propyl group, isopropyl group, butyl group, and 5ec-butyl group.

Table 1 shows typical novel hydantoin derivatives of the present invention.
Shown below.

The compounds represented by general formulas (2) and (3), which are raw materials for producing the compound of the present invention, are easily available;
The compounds represented by the general formula (2) include, for example, methyl bromide, methyl iosito, ethyl bromide, ethyl yosito, propyl bromide, propyl iosito, isopropyl bromide, isopropyl iosito, Butyl bromide, butyl iosito, isobutyl bromide, s, ec'-
Alkyl halogen compounds such as butyl bromide, pentyl iosito, isopentyl iosito, hexyl iosito, 1-methylpentyl bromide, 2-methylpentyl iosito, octyl bromide, 1-octyl iosito, dobu, cylbromide, cyclohexyl bromide, Cycloalkyl halogen compounds such as cyclopentyl bromide and cyclohexyl bromide, allyl chloride, allyl bromide, methallyl bromide, crotyl b[3-romide, crotyl chloride, 3-bromo-1-butene,
3-bromo-3-methyl-1-butene, prenylbromide, 4-bromo-2-methyl-1-butene, l-bromo-3-pentene, geranylbromide, 1,3-dichloropropene, 2. Unsaturated halogen compounds with double bonds such as 3-dichloropropene, 2,3-dibromo-1-butene, fluorohargyl chloride, propargyl bromide, propargyl iosito, 1-bromo-22-butyne, 1-chloro -2-butyne, 3-chloro-1-butyne, 3-pro-1-mo-butyne, 3-bromo-1-pentyne, 3-bromo-3-methyl-1-butyne, 3-chloro-3-methyl-1- Unsaturated halogen compounds with double bonds, such as butyne, 2-bromo-2-pentyne, 6-chloro-1-hexyne, l-bromo-3-pentyne, 4-bromo-1-butyne, or allyl alcohol , methallyl alcohol, 3-methyl-3-butene-1-
ol, 2-methyl-3-buten-2-ol, prenyl alcohol, geraniol, nerol, propargyl alcohol, 1-butyn-3-ol, 3-methyl-1
Unsaturated alcohols such as -butyn-3-ol and 1-butyn-4-ol, benzenesulfonic acid esters, p-toluenesulfonic acid esters, or sulfuric esters of ordinary aliphatic alcohols can be used.

Examples of the compound represented by the general formula (3) include methylbromide, methyl iosito, ethyl bromide, ethyl iosito, isopropylbromide, isopropyliosito, butyl bromide, butyl iosito, isobutyl bromide, 5ec-butyl bromide, pentyl iosito, isopentyl iosito, Alkyl halogen compounds such as hexyl iosito, 1-methylpentyl bromide, 2-methylpentyl iosito, octyl bromide, octyl iosito, dodecyl bromide, cyclopropyl bromide, cyclobe-16 = cycloalkyl halogen compounds, allyl Chloride, allyl bromide, methallyl chloride, methallyl chloride, crotyl bromide, crotyl chloride, 3-bromo 1-
Butene, 3-bromo-3-methyl-1-butene, prenylbromide, 4-bromo-2-methyl-butene, 4-bromo-3-methyl-1-butene, 1-bromo-3-pentene, geranylbromide , l,3-dichloropropene,
2,3-dichloropropene, 2,3-dibromo-I-
unsaturated halogen compounds with double bonds such as butene,
Prohargyl chloride, propargyl bromide, propargyl iosito, 1-bromo-2-butyne, 1-chloro-2-butyne, l-chloro-2-butyne, 3-chloro-
1-butyne, 3-bromo 1-butyne, 3-bromo 1
-pentyne, 3-bromo-3-methyl-1-butyne, 3
-Chloro-3-methyl-1-butyne, 2-7'lomo3
-pentyne, 1-bromo-3-pentyne, 1-bromo-
Unsaturated halogen compounds having a triple bond such as 2-pentyne, 6-chloro-1-hexyne, 1-bromo-3-pentyne, 4-bromo-1-butyne, or allyl alcohol, methallyl alcohol, 3-methyl-3 -buten-1-ol, 2-methyl-3-buten-2-ol,
Unsaturated alcohols and common aliphatic alcohols such as prenyl alcohol, geraniol, nerol, propargyl alcohol, 1-butyn-3-ol, 3-methyl-1-butyn-3-ol, 1-butyn-4-ol Sulfonic acid esters such as benzenesulfonic acid ester and p-toluenesulfonic acid ester, or sulfuric acid esters can be used.

The hydantoin derivative represented by general formula (4), which is a precursor for synthesizing the compound of the present invention, can be produced, for example, by the method shown below.

That is, nitrobenzene derivative (5) [wherein X and Y represent the same meanings as above. R5 is a lower alkyl group or an aralkyl group. ] in the presence of hydrogen, platinum oxide,
Reduction using a platinum-carbon or palladium-carbon catalyst gives the aniline derivative (6) [wherein xlY and R5
has the same meaning as above. ] and then treated with phosgene gas or trichloromethyl chloroformate to obtain isocyanate derivative (7) [in the formula,
X, Y and R5 have the same meanings as above. ]. Next, this isocyanate derivative (
7) and α-amino-α,β-unsaturated carboxylic acid ester (8) [wherein R3 and R4 independently represent a hydrogen atom or a lower alkyl group, and R'- represents a lower alkyl group. General formula (9) obtained by reacting with [where X, YSZ, R', R4, R' and R& have the same meanings as above. ] By treating the urea derivative represented by the formula (4) in the presence of an acid or a base, the hydantoin derivative represented by the general formula (4) can be obtained. (See Reference Examples below) Further, the urea conductor represented by the general formula (9), which is a raw material for manufacturing the hydantoin derivative represented by the general formula (4), can also be manufactured by the following method.

=21= That is, the urea derivative (10) obtained by reacting the isocyanate derivative represented by the general formula (7), which can be produced by the above-mentioned method from the nitrobenzene derivative (5) shown above, with ammonia ( During the ceremony,
X, Y and R5 have the same meanings as above. ] with the α-ketocarboxylic acid ester represented by the general formula (11) (wherein R3, R4 and R6 have the same meanings as above) in the presence of an acid catalyst, the general formula (9
) can be converted into the urea derivative represented by formula (4). Then, by treating this in the same manner as above in the presence of an acid or base, a hydantoin derivative represented by the general formula (4) can be obtained. . (See Reference Examples below) - Next, the present invention will be described in more detail with reference to Examples. In addition, the method for producing the raw materials used for producing the compound of the present invention is also shown below as a reference example.

Example 1 3-(2'-Fluoro-4'-chloro-51-hydroxyphenyl)-5-isopropylidenehydantoin (25 μmol, 91.7 μmol) was placed in a Nejiro test tube.
-Dimethylformamide (3ml) was added and dissolved. Potassium carbonate (70■) and methyl iodide (100
μm) and stirred at 40° C. for 9 hours. After the reaction was completed, saturated ammonium chloride aqueous solution was added and ether (3 ml x 3
extracted). The ether layer was washed with water (2 ml x 3 times) and dried over anhydrous magnesium sulfate. The drying agent was removed and the ether solution was concentrated under reduced pressure to precipitate a white solid, which was isolated by filtration.

This product is 1-methyl-3-(2'-fluoro-4'-
It is chloro-5'-methoxyphenyl)-5-isopropyridihydantoin, and the yield is 22cm (yield 80%).
Met.

24-Example 2 3-(2',4'-dichloro-5'-
Add hydroxyphenyl)-5-isopropylidenehydantoin (200μ, 0.66 mm o 1) and add N.
, N-dimethylformamide (20 ml) was added to dissolve the mixture, and then potassium carbonate (914 ml) and methyl iodide (4 g) were added and reacted at 40°C for 9 hours. After the reaction was completed, it was made acidic by adding IN hydrochloric acid and diluted with ether (20ml x
3 times).

The organic layer was washed with water (10 ml x 3 times) and then dried using anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a clear colorless oil. Ethanol was added, the mixture was cooled to -78°C, and the precipitated white solid (yield: 213 cm, yield: 98%) was collected by filtration. The spectrum confirmed that this product was l-methyl-3-(2',4'-dichloro-5'-methoxyphenyl)-5-isopropylidenehydantoin.

Example 3 1-Methyl-3-(2'-fluoro-
4'-chloro-5'-hydroxyphenyl) 5-isopropylidenehydantoin (965■, 3.2 mmol)
and N,N-dimethylformamide (25 ml) was added to dissolve it. Then, potassium carbonate (1.0 g) and 1,3-dichloropropene (2.8 ml) were added to the solution.
The mixture was stirred at ℃ for 4 hours.

After the reaction was completed, it was made acidic using IN hydrochloric acid, and ether (10
ml x 3 times). Water the organic layer (5 ml 1 x 3 times)
After washing with water, it was dried with anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a yellow oil (1,12
g) was obtained. It was purified using silica gel column chromatography (benzene/ethyl acetate = 4/1), and ■-methyl-3-(2'-fluoro-4'-chloro-5'-(
3'-Chloro-2#-propenyl)oxyphenyl)-
Yellow oil of 5-isopropylidenehydantoin (41
, 5s+g, yield 36%). This product can be isolated as a pale yellow solid by recrystallization from ethanol.

Example 4 In a eggplant-shaped flask, add 1 dimethyl J-3-(2'-fluoro-41-chloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (500 μm, 1.7 mm).
ol) and N,N-dimethylformamide (
20 ml) was added and dissolved. Potassium carbonate (1,1
4g) and 2,3-dichloropropene<1.54ml)
, and stirred at 4.0° C. for 5 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 washed with water (5ml x 3) and dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a yellow oil. Add methanol and
After cooling to 8°C, the precipitated solid (135 cm, yield 22%) was collected by filtration. From the spectrum, this substance is 1-methyl-3
-(2',4'-dichloro-5'-(2'-chloro-2
It was confirmed that it was #-propenyloxy)phenyl)-5-isopropylidenehydantoin.

Example 5 1-Methyl-3-(2'-fluoro-
41-Bromo-5'-hydroxyphenyl)-5-isopropylidenehydantoin (101■, 0.34mmol
l) and N,N-dimethylformamide (10 m
l) was added and dissolved. Add potassium carbonate (200μ) and propargyl bromide (350μ) and heat at 40°C for 5 minutes.
Stir for hours. After the reaction was completed, the filtrate was acidified using N hydrochloric acid and extracted with ether (10 ml x 3). 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. Ethanol was added and the mixture was cooled to -78°C, and the precipitated white solid (60 cm, yield 50%) was collected by filtration.

From the spectrum, this substance is 1-methyl-3-(2'-
It was confirmed that the product was dantoine on fluoro-41-bromo(5'-oxyphenyl)-5-isopropylidene.

Example 6 1-Methyl-3-(2'-fluoro-
41-p10mo5'-hydroxyphenyl)-5-isopropylidenehydantoin (13.0pl, ,0
．． ．． 38 m, m, , 01), and acetonitrile (15, m, 1) was added to dissolve it. , potassium carbonate, 4. , (2,,,/5■) and isopropyl iodine, do (65,0■) were added and stirred at 40°C for 20 hours.

After refluxing, acidify using IN hydrochloric acid and
, , (j, m, 1 x, 3 times). . Organic! was washed with heather (5 m, IX, 3 times) and dried with unheated sulfur agne and sium. Remove the desiccant 1. The solution was concentrated under reduced pressure to give a brown oil. Ethanol was added and the mixture was cooled to -78°C, and the precipitated colorless solid (70 cm, yield 47%) was collected by filtration. From the spectrum, this one is 1-
Methyl-1-(2'-fluoro-4'-bromo51-
It was confirmed to be isopropoxyphenyl-5-isopropylidenehydantoin.

Example 7 3-(2',4'-dichloro-5'-
Add propargyloxyphenyl)-5-isopropylidenehydantoin (150 μ, 0.44 mmol),
N,N-dimethylformamide (20 ml) was added and dissolved. Potassium carbonate (300 .mu.) and methyl iosite (630 .mu.) were added and stirred at 60.degree. C. for 14 hours. After the reaction was completed, it was made acidic using IN hydrochloric acid, and ether (10 ml
x3 times). The organic layer was washed with water (5 ml x 3) and dried over anhydrous magnesium sulfate. The desiccant was removed, the solution was concentrated under reduced pressure, and the pale yellow spectrum revealed that it was 1-methyl-3-(2',4'-dichloro-5'-propargyloxyphenyl)-5-isopropylidene. It was confirmed that it was hydantoin.

33-Example 8 3-(2',4'-dichloro-5'-
Add isopropoxyphenyl)-5-isopropylidenehydantoin (140 μ, 0.41 mmol) and add N.
N-dimethylbormamide (15 mN) was added and dissolved. Potassium carbonate (283 μN) and methyl iosite (6
00 ■) and stirred at 50°C for 1 hour.
The mixture was made acidic using N-hydrochloric acid and extracted with ether (5ml x 3). The organic layer was washed with water (3×3) 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 (120a
g, yield 83%). From the spectrum, this one is
It was confirmed that it was 1-methyl-3-(2',4'-dichloro-5'-isopropoxyphenyl)-5-isopropylidenehydantoin.

Example 9 1-Methyl-3-(2'-fluoro-
4'-Chloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (900cm, 3.0mm
o l), and acetonitrile (30 ml) was added to dissolve it. Potassium carbonate (1.02 g) and propargyl bromide (2.6 ml) were added and stirred at 40°C for 4 hours. After the reaction was completed, the mixture was made acidic using a saturated aqueous ammonium chloride solution and extracted with ether (10 ml x 3). The organic layer was washed with water (5 ml x 3) and dried over anhydrous magnesium sulfate. The desiccant was removed, and the precipitated white solid was collected by filtration and concentrated under reduced pressure, and further recrystallized from ethanol to obtain a white solid (264 cm, yield 26%). This product was confirmed by spectrum to be 1-methyl-3-(2'-fluoro-4'-chloro-5'-propargyloxyphenyl)-5-isopropylidenehydantoin.

Example 10 3-(2'-Fluoro-4'-chloro-5'-propargyloxyphenyl)-5-isopropylidenehydantoin (113 ml) was placed in an eggplant-shaped flask.

0.35 mmol) and added N,N-dimethylformamide (15 ml) to dissolve it. Potassium carbonate (246 .mu.) and ethyl iosite (550 .mu.) were added and stirred at 50.degree. C. for 5 hours. After the reaction was completed, 1/ION hydrochloric acid was added to make the mixture acidic, and the mixture was allowed to cool, and the precipitated colorless solid (93 cm, yield: 77%) was collected by filtration. The spectrum shows that this product is 1-ethyl-3-(2'-fluoro-4'-
It was confirmed that it was chloro5'-propargyloxyphenyl)-5-isopropylidenehydantoin.

Example 11 3-(2',4'-dichloro-5'-
Hydroxyphenyl)-5-isopropylidenehydantoin (30Q+w,i, Ommo 1) was added and acetonitrile (25ml) was added to dissolve it. Potassium carbonate (650■) and isopropylioside (1.7g
) was added and stirred at 50°C for 2 hours. After completion of the reaction, the mixture was acidified using IN hydrochloric acid and extracted with ether (20 ml x 3 times). The organic layer was washed with water <10ml x 3) and dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to obtain a clear colorless oil (330)w. This was recrystallized from chloroform-hexane to obtain a white solid (290 cm). This one is 3 depending on the spectrum
It was confirmed that it was -(2'4'-dichloro-5'-isoproboxyphenyl)-5-isopropylidenehydantoin.

Example 12 1-Methyl-3-(2'-)luoro-4'-bromo-5'-methoxyca, lupo, nyloxyphenyl)-5-isopropylidenehydantoin (1,0
3g, 2.57mmc+, j) and methanol (1
0 ml) was added and dissolved. Add potassium carbonate (5
0■)'' was added and stirred at 50°C for 2 hours. After the reaction I
Acidified with N-hydrochloric acid and diluted with ether (40 ml x 3 times)
Extracted with. 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) This was separated and purified by silica gel column chromatography (ethyl acetate:hexane-1:1) to obtain an oil (430cm). The spectrum shows that this product is almost pure 1-methyl-β-(,2'-fluoro-4'-
Bromo5.1-hydroxyphenyl)=5. - It was confirmed that it was isopropyridene hydantoin. It was further purified by silica gel column chromatography (ethyl acetate/chloroform-1/2) to produce a colorless transparent oil (3
19■, yield 36%) was obtained.

1-Methyl-3-(2'-fluoro-4'-bromo5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (6.5 g) in an eggplant-shaped flask.
, 17.6 mmo ]) and methanol (60 ml
) was added and dissolved. Potassium carbonate (2.5 g) was added and stirred at 40°C for 4 hours. After the reaction was completed, saturated ammonium chloride aqueous solution was added to make it acidic, and ether (30aex
3 times). The organic layer was washed with water (10 dXa times) and then dried over anhydrous magnesium sulfate. After removing the drying agent, the solution was concentrated under reduced pressure to obtain a brown oil. This was separated and purified by silica gel column chromatography (ethyl acetate). From the spectrum, this substance is l-methyl-3
It was confirmed that it was -(2'-fluoro-41-chloro-57-hydroxyphenyl)-5-isopropylidenehydantoin.

In an eggplant-shaped flask, add ← and #reference = 3-(2',4'-dichloro-5'-methoxycarbonyloxylaenyl)-5
-isopropyl, lydenhydantoin (?, 3 g
+, , 6.4 mmol) and dissolved in methanol (40d). Add potassium carbonate (50
0■) was added and stirred at 60°C for 1 hour. IN after reaction completion
The reaction solution was made acidic using hydrochloric acid, and ether (20+dx
3 times). The organic layer was washed with water (1 (for ldXa)) and dried over anhydrous magnesium sulfate. After removing the desiccant, the solution was concentrated under reduced pressure to give a pale yellow oil (1,9
3g) was obtained. Ether was added to this to precipitate 3-(
2',4'-dichloro-5'-hydroxyphenyl)
-5-isopropylidenehydantoin white solid (1'
, '02g) was collected by filtration. Further, the mother liquor was concentrated and ether was added to obtain a white solid (0.9 g). The response was quantitative. ,... Example 15 3-(2'-fluoro-4'-chloro-
・5'-Methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (110ag, "0.3
1 mmol) and potassium carbonate (54 cm) were added, and methanol (5?) was added to dissolve them.

This was stirred at 40°C for 3 hours. After the reaction was completed, a saturated ammonium chloride aqueous solution was added to make it acidic and ether (2 ml x
3 times). The organic layer was washed with water (2 ml x 3 times) and dried over anhydrous magnesium sulfate. The drying agent was removed and the 5-ether solution was evaporated under reduced pressure to form a brown oil (
67■, yield 77%) was obtained. The spectrum confirmed that this product was 3-(2'-fluoro-4'-chloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin.

3=(2'-fur, oro 4', -chloro-5'-ethoxycarbonyloxyphenyl)-5-isoprobily,
A methanol (20 μm) solution of Denhyanthine (204 μm, 0.57 mmol) and sodium carbonate (50 μm) was stirred at 40° C. for 3 hours.

After the reaction was completed, a saturated ammonium aqueous solution was added, and the mixture was extracted with ether (5d 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 brown oil. Ether was added to this to precipitate white crystals (16
2) was isolated by filtration. This product was found to be 3-(2'-fluoro-47-chloro-5
It was confirmed that it was 1-hydroxyphenyl)-5-isopropylidenehydantoin.

Example 17 e ·3-(2'·-"Fluoro-4'-chloro-5'-methoxycarbonyloxyphenyl)-5-(2#-butylidene)hydantoin (1.02 g.

3. Put Omrp o l) into an eggplant-shaped flask,
Methanol (40d) was added to dissolve. Potassium carbonate (230 ml) was added and allowed to react at room temperature for 15 hours.

After the reaction 1. Acidified with N-hydrochloric acid and diluted with ether (
10, dxa times). The organic layer was washed with water (5d x 3 times) and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure to obtain a colorless transparent oil (895 cm). This product is almost pure 3-(2'-fluoro-4'
・-Chloro-5'-hydroxyphenyl L; > -5-
, (2'-butylidene)hydantoin
Confirmed from R spectrum etc.

Example 18 In an eggplant-shaped flask, 1-methyl-3-(2'-fluoro-4'-chloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (200 g, 0.63 mm
o l) and N,N-dimethylformamide (2
0d).

Next, potassium carbonate (45 ml) was added and stirred at room temperature for 30 minutes. Cyclopropyl bromide (750 ml) was added and reacted at room temperature for 18 hours. After the reaction was completed, the mixture was made acidic by adding IN hydrochloric acid and extracted with ether (5-X 3 times). The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After removing the drying agent, the solution was subjected to S condensation under reduced pressure to obtain a pale yellow oil. This product was purified using silica gel column chromatography. This one is 1-methyl-3=(2'
-Fluoro-4'-chloro-5'-cyclopropyloxyphenyl)-5-isopropylidenehydantoin (1
It was confirmed by NMR spectrum, etc.

Example 19 3-(2',4'-dichloro-5'-
Hydroxyphenyl)-5-isopropylidenehydantoin (105N, 0.35 mmol) was added and acetonitrile (5-) was added to dissolve it.

Next, potassium carbonate (60 μ) and cyclohexyl bromide (350 w) were added and reacted at 50° C. for 24 hours. After the reaction was completed, the mixture was directly concentrated under reduced pressure, and the solvent and excess cyclohexyl bromide (5-) were added, followed by stirring at 40°C for 2 hours. 0 after completion of reaction. The mixture was acidified with IN hydrochloric acid and extracted with ether (2-X 3 times). The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After removing the drying agent, the solution was concentrated under reduced pressure to obtain a clear colorless oil. By purifying this product by silica gel column chromatography, l-methyl-3-(2',4'-
dichloro-5'-cyclohexyloxyphenyl)-5
- Colorless transparent oil of isopropylidenehydantoin (6
0■) was obtained. The desired product was recrystallized from ethanol as a white solid (20 cm).

A yield of 14%) was obtained.

Example 20 3-(2',4'-dichloro-5'-isopropoxyphenyl)-5-isopropylidenehydantoin (15
2w, 0.446 mmol) was placed in an eggplant-shaped flask and dissolved in N,N-dimethylformamide (20ad). Potassium carbonate (362 .mu.) and propargyl bromide (600 .mu.) were added and stirred at room temperature for 13 hours. After the reaction was completed, the mixture was acidified using IN hydrochloric acid and extracted with ether (5-X 3 times). The organic layer was washed with water (3dXa times) and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the mixture was concentrated under pressure to obtain a pale yellow oil (170 cm).

This product was confirmed to be l-propargyl-3-(2',4'-dichloro-5'-isopropoxyphenyl)-5-isopropylidenehydantoin from NMR spectra and the like. The yield was quantitative.

52-Example 21 3-(2',4'-dichloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (970w
, 3.22 mmol 1) in N,N-dimethylformamide (40 m), added potassium carbonate (702 μl) and propargyl bromide (2,9+ ml) at 50°C for 4 hours.
The mixture was further stirred at 80°C for 8 hours. After the reaction was completed, the mixture was made acidic with IN hydrochloric acid and extracted with ether (2 (ldX 3 times)). After washing the am with water, it was 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). Ether was added, the mixture was cooled, and a precipitated white solid (193 cm) was collected by filtration.

According to NMR spectroscopy, this product has a 3-(2',4'-
dichloro-5'-propargyloxyphenyl)-5-
It was confirmed that it was isopropylidenehydantoin.

Furthermore, by concentrating the filtrate and recrystallizing it from chloroform-hexane, a propargyl group was also introduced on the 1-N position of the hydantoin ring, 1-propargyl-3-(2', 4
'-dichloro-5'-propargyloxyphenyl)=
White crystals of 5-isopropylidenehydantoin (694
(2), yield 57%) was obtained.

Example 22 3-(2-fluoro-4'-bromo-5'-hydroxyphenyl)-5-isopropylidenehydantoin (2
1 (Igt 0.64 mmo 1) was placed in an eggplant-shaped flask, and acetonitrile (10d) was added to dissolve it. Potassium carbonate (470 .mu.) and propargyl bromide (800 .mu.) were added to this, and the mixture was stirred at 40.degree. C. for 4 hours. After the reaction was completed, IN hydrochloric acid was added to make an acidic solution, and the mixture was allowed to stand at room temperature. The precipitated crystals (240 μm, yield 93%) were isolated by filtration.

From the NMR spectrum etc., this product is 1-propargyl-
It was confirmed that it was 3-(2'-fluoro-41-promo-5'-propargyloxyphe3yl)-5-isopropylidenehydantoin.

-56= Example 23 3-(2',4'-dichloro-5'-hydroxyphenyl)-5-isopropylidenehydantoin (1,0g
, 3.3 mmol 1) was placed in an eggplant-shaped flask, and acetonitrile (40 ml) was added to dissolve it. Potassium carbonate (2,4 g) and 1,3-dichloropropene (3,7 g
) and stirred at 60°C for 10 hours. After the reaction was completed, the precipitated solid matter was filtered off, the filtrate was washed with water (20 ml x 3 times), and then dried over anhydrous magnesium sulfate. The drying agent was filtered off and the filtrate was concentrated under reduced pressure to give a yellow oil (1.62 g).
I got it. This product was separated and purified by silica gel column chromatography to obtain the desired 1-(3'-chloro-
2'-propenyl)-3-(2',4'-dichloro-s
#<3///-chloro-2″′-propenyloxy)phenyl)-5-isopropylidenehydantoin (1
, 41 g, yield 94%).

This product is a mixture of four types with different stereochemistries of the chloropropenyl group on the nitrogen atom at the 1st position of the hydantoin ring and the chloropropenyl group on the oxygen atom at the 5th position of the phenyl ring. The ``-8'' and E-8'' bodies were separated from 1 by lamb chromatography or recrystallization, and their 400MHz LH-NMR spectra were measured to confirm their structures. hydroxyphenyl)-5-isopropylidenehydantoin (
210w, 0.64mm o I) 0) 7 Potassium carbonate (470ml) in setonitrile solution (10ml)
(2) and 1,13-dichloropropene (710 ■) were added and stirred at 80°C for 3 hours. After the reaction was completed, IN hydrochloric acid was added and the mixture was extracted with ether (5 ml x 3). Dilute the organic layer with water (3
mlx (3 times) and then dried over anhydrous magnesium sulfate. After removing the desiccant, the solution was concentrated under reduced pressure to give a yellow oil (310 cm). This product was subjected to silica gel column chromatography (ethyl acetate/hexane-1/
2), 1-(3'-chloro-2'-propenyl)-3-(2'-fluoro-4#-bromo-5
'-(3'''-chlorotl11-2-propenyloxy)phenyl)-5-isopropylidenehydantoin (
202■, yield 58%) was obtained. This is a mixture of four types of isomers with different stereochemistry of the olefin of the chloropropenyl group on the nitrogen atom and the oxygen atom, and E-8
The body was separated and purified using column chromatography, and the structure was confirmed using 4'OOMHZHNMR.

60-Example 25 3-(2,'-Fluoro4'-bromo5'-hydroxyphenyl)-5-isopropylidenehydantoin (
214N, 0.65 mmol) acetonitrile solution (12 ml), potassium carbonate (450 μ) and 2
．． 3-dichloropropene (750 ml) was added and stirred at 50°C for 5 hours. After the reaction was completed, 0.1N hydrochloric acid was added, and the mixture was extracted with ether (4 nil x 3 times). The organic layer was diluted with water (2
mlx3 times) and dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure to give a yellow oil.

This product was separated and purified by silica gel column chromatography (ethyl acetate/hexane-1/2).
(2'-chloro-12'-propenyl)-3-(2・“
-Fluoro-4#-bromo5'=<2 ///-chloro-2-propenyloxy)phenyl)-5,-isopropylidenehydantoin pale yellow oil (230■
. . . Yield 74%) was obtained.

Implementation, Example 261.

3-(2'-Fluoro-4'-chloro-5'-hydro-xyphenyl)-5-(2'-butylidene)hydantoin (1'70■, 0-57 m m 'o'I)
Potassium carbonate (170 iw) and methyl iosite (
500 µm of the mixture was added and stirred at room temperature for 2 hours.

Add 3N hydrochloric acid and add ether 1. (10 ml×3 times). Yes4. The organic layer was washed with water (5ml x 2 times) and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure and the resulting pale yellow oil was separated and purified by silica gel column chromatography to obtain 1-methyl-3-(2'-fluoro-41-chloro-5'-methoxyphenyl). A colorless thin form of -5,,7(2'-butylidene)hydantoin -' (180 μm, yield 97%) was obtained.゛Reference Example 1 After the completion of the diacid reaction in a solution of 2-fluoro-4-chloro-5-methoxycarbonyloxynitrobenzene (52.1 g, 0.24 mol) in ethanol (60 Qml), the catalyst was filtered off, and the resulting pale The solvent was distilled off from the yellow transparent solution under reduced pressure to obtain a pale reddish brown oil. This product was confirmed by NMR spectrum to be substantially pure 2-fluoro-4-chloro-5-methoxycarbonyloxyaniline. This product can be purified by silica gel column chromatography and used as it is in the next reaction.

'H-NMR (CDCIs, TMS, ppm): δ 3
．． 86 (3H, s), 4.13 (2H.

br s), 6.48 (IH, d, JNF=8Hz
), 6.92 (IH, d, JNF=10H2).

Reference Example 2 A solution of 2-fluoro-4-bromo-5-methoxycarboniJ leoxynitrobenzene (30.4 g, O, Imo summer) in ethanol (300 ml) was stirred until platinum dioxide stopped. After the reaction was completed, the catalyst was added. The mixture was filtered and the solvent was distilled off from the solution under reduced pressure to obtain a brown solid (28.0 g) of 2-fluoro-4-bromo-5-methoxycarbonyloxyaniline.

'H-NMR (CC14, TMS, ppm): 63.8
3 (3H, s), 5.01 (2H.

' br s), 6.63 (IH', d, JM
F-7, 6Hz), 7', 06 (IH, d, JMF=
9.8Hz).

M) Trichloromethyl chloroformate (19 ml, 1
2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (21.9 g, 100 mmol) was added to a solution of 58 mmof) in ethyl acetate (200 ml).
) in ethyl acetate (100 ml) was added dropwise over 20 minutes. After the dropwise addition was completed, the mixture was heated to 80°C and ethyl acetate was distilled off.

After cooling, carbon tetrachloride (150 ml) was added and left overnight.

After filtering off insoluble matter, the solvent was distilled off from the filtrate under reduced pressure to obtain a pale solution of 2-fluoro-4-chloro-5-methoxylponyloxyphenylisocyanate (20.6 g, yield 84%). A brown solid was obtained.

'H-NMR (CDC13, TMS, ppm): 63.
88 (3H, s), 6.97 (IH.

d), 7.37 (IH, d).

IR (KBr dlsk, elm-'): 226
0゜1 770゜Reference Example 4 Trichloromethyl chloroformate (15ml
1.125 mmol) of ethyl acetate (150 ml) tl
2-fluoro-4-bromo-5-methoxycarbonyloxyaniline (28.0 g, 113 m
A solution of mo 1) in ethyl acetate was added dropwise over 20 minutes. After the dropwise addition was completed, the mixture was heated to 80°C and ethyl acetate was distilled off. After cooling, carbon tetrachloride (150 ml) was added, insoluble matter was filtered off, and the solvent was distilled off from the filtrate under reduced pressure to obtain 2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl isocyanate (29.1 g). A brown solid was obtained (yield 94%).

'H-NMR (CC1a, TMS, I)pm): δ 3
．． 87 (3H, s), 6.89 (IH.

d, Jwy-6,8Hz), 7.31 (IH, d.

J□=8.6Hz).

IR(KBr d i sk, (!II-'): 2
260°=69− Reference Example 5 0.

2-Fluoro-4-chloro-5-ethoxycarbonyloxyphenyl isocyanate (16.7 g.

Ammonia gas was introduced into a solution of 64 mmol) in benzene (300 ml) with vigorous stirring 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 then dried. This product was the desired 2-fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (14.2 g, yield 80%).

' HN M R (CD Cl s CD s OD
, TMS.

ppm): 6 1.37 (3H,t, J=7
．． 2Hz), 4.30 <2H, q, J=7.21(
z), 7.10 (IH, d, 'JMF=10.2H
z), 8.07 (IH, d, J) IF=7.2Hz
).

Reference Example 6 δ 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
The white solid precipitated by the acid analysis was filtered, thoroughly washed with penzene, and dried. This product is the desired 2-fluoro-4
-Chloro-5-methoxycarbonyloxyphenylurea (10.3 g, yield 78%) was confirmed by NMR spectrum and the like.・LH-NMR (DMso-d, TVS, ppm):
δ 3.87, (3H, s), 5.81 (2H, br
s), '7.12 (IH, d.

JNF-'10Hz), '8.28 (IH,, d.

JHr=7.2Hz), 8.48 (IH, brS).

Reference Example 7 172 = 2-Fluoro-4-bromo-5-methoxylponyloxyphenylisocyanate (47.7 g, 164 mmol 1) was prepared in the same manner as in Reference Example 6. 5-methoxycarbonyloxyphenylurea (37.7 g', yield 75%) was obtained.

' HN M R (CD CI 3CD s OD,
TMS.

ppm): δ 3.83 (3H,S).

7.28 (I H, d, JIIF'= 1'O
H2).

7.99 (IH, d, J□=7.2, H, z).

Reference Example 8 - 〇-73~ 2,4-dichloro-5-methoxycarbonyloxyphenyl synthesized by the same operation as Reference Examples 1 to 4 using 2,4-dichloro-5-methoxycarbonyloxynitrobenzene as a raw material Isocyanate) (5.04g, 1
In a solution of 9.2 mmol 1) in benzene (120 ml),
Ammonia gas was introduced while stirring vigorously under water cooling.

After extraction for 30 minutes, the precipitated white solid was filtered and thoroughly washed with benzene.

1. This product is the desired 2,14-dichloro-'5-hydroxycarponyloxyphe, nylurea (4,6B6° yield 88%). Confirmed by H-NMR.

’HNMR(CDC13DMSO”di.

'TMS, p・pm) :'63.88 (3
-H.

s), F35'(2H, b r), "L'4'5<l
H,'s), 8.20 (1'H,'b r),'8
．． 32 (IH; s), Reference Example 9 To 1 2-fluoro-4-chloro-5-methoxycarbonyloxyphenylsocyanate (2,4
5g; 1.0 m, m 64) and benzene (
L (1 (1 ml)) and then dehydrova, phosphorus ethyl ester (1,41 g + 10 m'mo 1.
) was added thereto, and the mixture was allowed to react at room temperature for 110 hours. The precipitated solid was removed, and a saturated aqueous ammonium chloride solution was added to the solution, followed by extraction with ether (100 ml x 3 times). The organic layer was washed with water (3 times 50ml) and then dried over anhydrous magnesium sulfate. The stem desiccant was removed and the solution was concentrated under reduced pressure. Precipitated N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) -N
'-(1'-ethoxycarbonyl-2'-methyl-1'
A white solid (3.45 g) of -propenyl) urea was collected by filtration. The yield was 92%.

'HNMR(CDsSOCDs CDCl5°TMS
, ppm): δ 1.27 (3H, t.

J=6.9Hz), 1.87 (3H, s).

2・12 (3H・°)・3・86 (3H,s)・4
,．． 20 (2H,,Q, J=6.9Hz),
, 6.14 (1, H, br, s) , 7.05
, (IH, d.

JHly-9,9Hz), 7.35 (IH,brs
), 8.11 (1, H, d, J+<F77.2Hz)
.

IR(K,Br d i sk, cm-',),
: 1.770° Reference Example 10 I 2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl isocyanate (1,2
8 g, 4.41 mmol) and benzene (100 m
1) and then dedrovaline methyl ester (63
0 mg, 4.88 mmol) was added thereto, and the mixture was reacted at room temperature for 10 hours. The precipitated solid was removed, and a saturated aqueous ammonium chloride solution was added to the solution, followed by extraction with ether (100 ml x 3).

The organic layer was washed with water (50 ml x 3 times) and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solution was concentrated under reduced pressure. Precipitated N-(2-fluoro-4-bromo-5-methoxycarbonyloxyphenyl)-N'
-(1'-methoxycarbonyl-2'-methyl-11-
A white solid (483 cm) of propenyl urea was collected by filtration.

Ether was added to the filtrate and the mixture was cooled to further precipitate a white solid (385 cm), which was the desired product, and was able to be obtained by filtration. The total yield was 47%.

' HN M R (CD 3 S OCD s CD
Cl s.

TMS, I) 1) m), Knee δ 1. ．． 83 (3I(
, s).

2.03 (3H, s), 3. ．． 67 ,,(3H,,
a).

3. 86 (3H, s) t, 7.25 <IH,
d.

JHv710.5Hz), 7.84 (LH, brs)
+-,8,23(l Hl, d, JllF=
6.911. s).

111.58 (IH,,br　s).

I R(KB r -d 1. s k, am-'
), +1770°1730, , ・ ・ Reference Example 11 2,4-dichloro-5-methoxy synthesized according to the method shown in Reference Examples 1 to 4 using 2,4-dichloro-5-methoxycarboxyloxynitrobenzene as a raw material Carbonyloxyphenyl isocyanate (1,31g, 5mm
o l) into an eggplant mold (7 laths: I), add benzene (1
00 ml) was added thereto, followed by dehydrovaline methyl ester (0.65 g, 5 mmol) and reacted at room temperature for 7 hours. A small amount of precipitated solid was removed, and the solution was mixed with ammonium chloride aqueous solution (50 ml x 3 times) and water (50 ml x 3 times).
Washed twice). After drying, the solvent was distilled off from the solution under reduced pressure to obtain a brown oil (1.35 g). A mixed solution of ethyl acetate and hexane was added to this, and the precipitated N-(2,4-dichloro-5-methoxycarbonyloxyphenyl)-N
'-(1'-methoxycarbonyl-2'-methyl-1'
-propenyl) urea as a white solid (1.31 g, yield 58
%) was collected by filtration.

'H-NMR (CDCIs, TMS, ppm): 61.
91 (3H, s), 2.17 (3H.

s), 3.68 (3H, s), 3.88 (3H.

s) 6.63 <IH,br s), 7.31(IH
, br s), 7.35 (IH, s).

8.30 (IH, s).

IR (KBr disk, cm-'): 1770
゜-8〇- Reference Example 12 2-Fluoro-4-chloro-5-ethoxycarbonyloxyphenylurea (10.1 g, 36.4 mmol) and a small excess of methyl 2-oxoisovalerate (5.2 g) in benzene ( A catalytic amount of P-)luenesulfuric acid (6G+w, 0.35 mmol 1) was added to the 100 ml solution and heated under reflux for 4 hours. After the reaction was completed, the mixture was allowed to cool, and the precipitated solid was filtered off. 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 one is 'H-NMR
The spectrum shows that although it contains a small amount of the cyclized product 3-(2'-fluoro-4'-chloro-5'-ethoxycarbonyloxyphenyl)-5-isopropylidenehydantoin, it does not contain the desired N-(2- Fluoro-4-chloro-5-ethoxycarbonyloxyphenyl)-N'-
(1'-ethoxycarbonyl-2'-methyl-1'-propenyl)urea.

This mixture can be used in the following reaction reference example 1 without separation and purification.
2-Fluoro-4-promo-5-methoxycarbonyloxyphenylurea (15.2 g, 50
mmo 1) and 2-oxoisokichito (169) were added, and the mixture was heated under reflux for 20 hours.

After the reaction is complete, add saturated ammonium chloride aqueous solution (
Add ether (100ml x 3) to make it acidic.
extracted). The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After filtering off the desiccant, the solution 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. These products all contain the target N
-(2-Fluoro-4-bromo-5-methoxycarbonyloxyphenyl)-N'-(1'-ethoxycarbonyl-2'-methyl-1'-propenyl)urea was confirmed by 'H-NMR. did. The total yield was 28%.

'HNMR (CDCls+TMS, ppm): δ
1.26 (3H, t, J=7.2Hz).

1.83 (3H, s), 2.07 (3H, a).

3.87 (3H, s) 4.19 (2H, q, J=7.
2Hz), 7.08 (IH,, br s), 7.18
(I Hd, Juv-10, 5H2), 7.74 (IH
, b, r s), 8.16 (IH, d.

J Hv-7, 2H1).

Reference Example 14 I 2,4-dichloro-5-methoxycarbonyloxyphenylurea (10.3 g) was placed in a 200 ml eggplant flask equipped with a Dean-Stark apparatus.

37mmo 1), ethyl 2-oxoisovalerate (9
,0g) and benzene (150ml) as a solvent, then p-)luenesulfonic acid (644g) as a catalyst.
) and heated under reflux for 7 hours. After completion of 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 give a brown oil (17
, 4g) was obtained.

Recrystallization from ethyl acetate-hexane solvent system yields N-(2,4-dichloro-5-methoxycarbonyloxyphenyl)-N'-(1'-ethoxycarbonyl-2
A white powder of '-methyl-11-propenyl)urea (7.0 g, yield 47%) was obtained.

'H-NMR (CDC1a, TMS, ppm): δ 1
．． 27 (3H, t, J=7.5Hz).

1.93 (3H, s), 2.18 (3H, s).

3.88 (3H, s), 4.22 (2H, q.

J77.5Hz), 6.62 (IH, br　s).

7.31 (IH,,br S), 7.36 (IH
.

s), 8.30 (IH, s).

three. Example 15 N-(2-fluoro-4-chloro-5
-methoxycarbonyloxyphenyl)-〆N'-(1'-vtoxycarbonyl or←--2'-methyl-1'-propenyl)urea (2.53 g, 6.5 mm
o l) and sodium acetate (140 ml) were added, toluene (80 ml) was added, and the mixture was reacted under reflux for 7 hours. After the reaction was completed, ethyl acetate (30 ml) was added to this, and water (
20 ml×3 times). The solution was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a brown oil.

3-(2'-fluoro-4') precipitated by adding ether
-chloro-5'-methoxycarbonyloxyphenyl)
-5-isopropylidenehydantoin white solid (1,
11 g) was collected by filtration. The mother liquor was further concentrated and ether-
A solid (386 cm) precipitated by adding a hexane mixed solvent was collected by filtration. The total yield was 67%.

'H-NMR (CD, C10, TMS, ppm): δ
1.8? (3H,S), 2.26 (3H.

s), 3.91 (3H, S)', 7.26 (IH.

d, JllF=6.9H2), 7.31 (IH, d.

JIIF=9.0H2), 9.10 (IH,brS)
,゛IR (KBr disk, cm-'): 1780゜Reference Example 16 N-(2-fluoro-4-pro￥-5
-methoxycarbonyloxyphenyl)-N'-(1'
-Methoxycarbonyl-2'-methyl-1'-propenyl)urea (5.66 g.

13.5 mmol 1) was added thereto and toluene (90 ml) was added to dissolve it. Sodium acetate (114 cm) was added and the mixture was heated under reflux for 3 hours. After cooling the reaction mixture, the precipitated solid was removed, and the solution was washed with water (50 ml x 3 times).
It was dried with anhydrous magnesium sulfate. The solution was concentrated under reduced pressure and ether was added to precipitate 3-(2'-fluoro-4
'-promo 5'-methoxycarbonyloxyphenyl)-5=white crystals of isopropylidenehydantoin (1
, 50g) was obtained. A further white solid (1.94 g) was collected by filtration by concentrating the filtrate and adding ether.

The total yield was 68%.

'HNMR (CDCIs, TMS, ppm): δ 1.
86 (3H, s), 2.25 (3H.

s), 3', 91 (3H', s), 7.2
9 (IH.

d, JIIF"8.'7H'Z), 7.50 (IH,
d.

J, Ir=9.0H2'), 9. 'O'? (
IH,brS), IR(KBrd'i'lk,cs-'): 178
0°1730.1seo.

Reference Example 17 N-(2,4-dikurow-52methoxycarbonyloxyphenyl)'-N'-(1'-
Methoxycarbonyl-2'-meno-1'-propenyl)urea (6.76 g, 17.3 mmol) was added, and benzene (60 ml) was added.

Next, sodium acetate (149 cm) was added and the mixture was heated under reflux for 7 hours. After the reaction was completed, the reaction solution was cooled and the precipitated solid was removed. The filtrate was washed with water (50 ml x 3 times) and dried, and the solvent was distilled off under reduced pressure to obtain a brown oil. Add chloroform (1'00ml) and precipitate 3-
White crystals (3.97 g, yield 64%) of (2',4'-dichloro-51-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin were obtained.

'H-NMR (CDCI3', TMS, ppm): 61
．． 89 (3H,s), 2.28' (3H.

's), 3.92 (3H,s), 7.28 (IH
.

s)+' 7.63 (IH, s), 8.96 (1'
H.

br s), 'IR (KBr dlsk, cm-'): 17'80°1720.1680° Reference Example 18 N-(2-fluoro-4-chloro-5-ethoxycarbonyloxyphenyl)-N'-(1 '-Methoxycarbonyl-2'-methyl-1'-propenyl)urea (1,3
7 g + 3.5 mmol) of benzene (20rnl
) Sodium acetate (300 ml) was added to the solution 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 an ether-pentane solvent system to give 3-(2'-fluoro-4'-chloro-5'-ethoxycarbonyloxyphenyl)-5-
Pale yellow solid of isopropylidenehydantoin (1,24
g5 yield 96%) was obtained.

'H-NMR (CD'Cl s, TM'S, 'P
p'm): δ 1.40 (3H, t, J=6.8
Hz).

1.94 (38, s), 2.30 (3'H', s).

4.35 (2H, q,, J”6.8Hz).

7.2g (1 H; s) r7.41 (I
H,'d.

J+<r-'2.8Hz), 8.02(IH,"b'r
S).

Reference Example 19 N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) Urine!, (4g, 15.2
mmol) and methyl 3-methyl-2-oxovalerate (
A solution of 3.4 g; 23.6 mmol l') and the catalyst, 'p-1 toluenesulfonic acid (500 μl) in benzene (100 ml) was heated under reflux for 5 hours. After the reaction was completed, precipitated The solid was separated by filtration, and the filtrate was washed with water and 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 is N-(2-fluoro-4-
Chloro-5-methoxycarbonyloxyphenyl)-N
'-(1'-methoxycarbonyl-2'-methyl-1'
-butenyl) urea from the NMR spectrum.
! Approved.

'HNMR (CDCIs, TMS, pI): δ
1.03and1.12 (tota 13H,e
ach t, J=7.5Hz).

1.87 and 2.10 (total 3H.

each s),, 2.25and2.50(tot
, al 2H, each q, J=7.5Hz),
3.75 (3H, s), 3.87 (3H, s), 6
．． 48 (IH, br s).

=96-7.08 (IH,d, JNF=10.5H2
).

7.18 (IH, br s), 8.15a
nd8.18 (total IH, each,
d.

J-pei ? /=s　,OHZ　＞　.

The obtained disubstituted urea was then converted into 1)-) luenesulfone #
Toluene (100ml) using (500■) as a catalyst
The mixture was heated under reflux in a solvent for 9 hours. After the reaction was completed, the precipitated solid was filtered off, and the filtrate was washed with water. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off and recrystallized from an ether-hexane solvent system to give 3-(2'-fluoro-4'-chloro-5-methoxycarbonyloxyphenyl)-5. =(2'-Butylidene)hydantoin white crystals (2.05 g, yield 38%) were obtained.

'HNMR (CDC13, TMS, pI)m)'6
1.07and1.18 (tota 13H, eac
ht, J-7,5Hz).

1.65 and 1.87 (total 3H.

each s), 2.17and, 2.75(
total 2H, each q, J=7
．． 5H2), 3.98 (31(,s), 7
．． 25 (IH, d, JHF=3H2), 7.3
5 (IH, d, JMF=4.5H2), 8.7
8 (IH, m).

Reference Example 20 3-(2'-Fluoro-41-chloro-5'-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (8.1 g, 22.7 mm) was placed in an eggplant-shaped flask.
o l) and N,N-dimethylformamide (20
0 ml) was added and dissolved.

Potassium carbonate (16,9 g> and methyl iosite (15
ml) and stirred at 40°C for 4 hours. After the reaction was completed, the mixture was made acidic using a saturated aqueous ammonium chloride solution and extracted with ether (100 ml x 3). The organic layer was diluted with water (50
m 1 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 spectrum to be 1-methyl-3-<2'-fluoro-4'-chloro-5'-me(xycarbonyloxyphenyl)-5-isopropylidenehydantoin.

'H-NMR (CDCIs, TMS, ppm): δ 2
．． 1? (3H,S), 2.34 (3H.

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

7.27 (IH, d, J□=2.9H2), 7.
40 (IH, d, JllF=4.5Hz).

Reference Example 21 U 3-(2'-Fluoro-41-bromo-51-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (1.5 g, 3.7 mmo
I) and N,N-dimethylformamide (70m
l) 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 IN 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 transparent oil (1.27 g, yield 81%).
) was obtained. From the spectrum, this substance is 1-methyl-3
It was confirmed that it was -(2'-fluoro-4'-bromo-51-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin.

'HNMR (CDC1z, TMS, pI)m): 6
2.17 (3H,s), 2.34 (3H.

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

s), 6.78 (IH, d, Js+y=6H2).

7.41 (IH, d, JHF=9H2).

Reference Example 22 3-(2'/,4'-dichloro-51
-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin (602■.

1.68 mm o 1 ) was added thereto, and N,N-dimethylformamide (30 ml) was added to dissolve it. Potassium carbonate (1.2 g) and methyl iosite (2.5 g) were added and stirred at 50° C. for 2 hours. After the reaction was completed, the mixture was acidified using IN hydrochloric acid and extracted with ether (20 ml×s). The organic layer was washed with water (10 ml x 3) and dried using anhydrous magnesium sulfate. The desiccant was removed and the solvent was concentrated under reduced pressure to give a colorless transparent oil (570 cm, yield 91
%) was obtained. From the spectrum, this substance is 1-methyl-3
-(2'.

It was confirmed that it was 4'-dichloro-51-methoxycarbonyloxyphenyl)-5-isopropylidenehydantoin.

'H-NMR (CDCIs, TMS, ppm): δ 2
．． 16 (3H, s), 2.33 (3H.

s), 3.39 (3H, s), 3.88 (3H.

s), 7.28 (IH, s), 7.60 (IH.

S).

The compound of the present invention thus obtained has excellent performance as a herbicide, as described above.

When using the compound of the present invention as a herbicide, it can be used as it is, but generally it can be used as a herbicide by mixing one or several types of adjuvants.Usually, the adjuvants include various carriers, It is preferable to mix fillers, solvents, surfactants, stabilizers, etc. and formulate the formulation in the form of wettable powders, emulsions, powders, granules, etc. by conventional methods.

Examples of the solvent, which is one of the adjuvants in the herbicide containing the compound of the present invention as an active ingredient, include water, alcohols, ketones, ethers, aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, and acids. Amides, esters, nitriles, etc. are suitable, and one or a mixture of two or more of these may be used.

In addition, as fillers, mineral powders such as clays such as kaolin and bentonite, talcs such as talc and pyrophyllite, oxides such as diatomaceous earth and white carbon, soybean powder, and C
Vegetable powders such as MC are preferred, and one or a mixture of two or more of these is used.

Additionally, surfactants may be used as spreading agents, dispersants, emulsifiers, and penetrants. Examples of the surfactant include nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants.

These surfactants are used singly or as a mixture of two or more depending on the purpose.

Preferred methods of using the herbicide containing the compound of the present invention as an active ingredient include soil treatment, water surface treatment, foliage treatment, etc., and particularly excellent effects can be achieved by applying the herbicide before the germination of the pest control lotion to when it is young. be able to.

In addition, this herbicide may be mixed or used in combination with other active ingredients that do not inhibit the herbicidal activity of this active ingredient, such as other herbicides, insecticides, fungicides, and plant growth regulators. It is possible.

Next, the present invention will be explained in more detail by giving examples of formulations of herbicides containing the compounds of the present invention as active ingredients, and test examples of the herbicidal effects of the herbicides. Note that parts indicate parts by weight.

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) A mixture of 50 parts of the compound of the present invention, 25 parts of diatomaceous earth, 22 parts of clay, and 3 parts of Lunosox R100C (manufactured by Toho Chemical Co., Ltd.) is evenly mixed and pulverized to prepare 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, and the mixture is made into granules using an extrusion granulator, followed by drying and sizing to form granules.

Test Example 1 (Efficacy against paddy field weeds) A Wagner pot with a size of 1/5000 are filled with paddy soil, and seeds of Japanese barnyard grass, Japanese grasshopper, and Japanese grasshopper and rice seedlings at the 3- to 4-leaf stage (variety: Nipponbare) were placed in this.・ Seed or transplanted and kept it in a flooded state. After 5 days, the active ingredient of the herbicide of the present invention was made into granules according to Formulation Example 3.
A predetermined amount was treated on the water surface so that On the 30th day after the granule treatment, the herbicidal effect on the test plants and the chemical damage to the rice plants were investigated using the following criteria. 100 1: 61-80 2: 41-60 3: 21-40 4: 6-20 5: 0-5 Drug damage: Growth rate.

, 4+1 +: Slight damage 10+: Minor damage +++: Medium damage + 10++: Severe damage Then, as weeds, weeds such as crabgrass, white grass, and staghorn beetle were sown, and as a crop, soybean seeds were sown, and 1c11 of soil was covered on top of the seeds.

The next day, the diluted solution of the hydrating powder shown in Autopsy Example 2 was prepared as follows: 20.10.5. 20 days after treatment, the herb-killing effect and chemical damage were investigated in the same manner as in Test Example 1. The results were tested in the 1st test Example 3 (Effect of foliage treatment) 1/5,000
Earle's Wagner pots were filled with field soil, and weeds such as corn, whiteweed, knotweed, and dogweed were sown there.
After 20 days, a chemical solution of a predetermined concentration, prepared by diluting each test compound prepared in the emulsion shown in Formulation Example 1 with water, was applied to the stems and leaves of weeds grown after 20 days, and the test plants were uniformly sprayed with water at a ratio of 1001/10a. Sprayed. 20 days after treatment, the herbicidal effect and drug damage were evaluated in the same manner as in Test Example 1.

Claims (1)

[Claims] General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, X and Y represent halogen atoms. 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 each independently represent a hydrogen atom or a lower alkyl group. A hydantoin derivative represented by ].