WO1998011107A1

WO1998011107A1 - Bicyclic hydantoin derivatives, process for producing the same, and herbicides containing the same as active ingredient

Info

Publication number: WO1998011107A1
Application number: PCT/JP1997/003120
Authority: WO
Inventors: Kenji Hirai; Natsuko Okano; Ryuta Ohno; Tomoyuki Yano; Kazuhisa Ikemoto; Tomoko Yoshii; Sadayuki Ugai; Osamu Yamada; Takuya Ueda
Original assignee: Sagami Chemical Research Center; Karen Pharmaceutical Co., Ltd.
Priority date: 1996-09-12
Filing date: 1997-09-05
Publication date: 1998-03-19
Also published as: JPH1087663A; AU4135297A

Abstract

Novel bicyclic hydantoin derivatives having excellent herbicidal activities and a high safety for crops and represented by general formula (1) are produced by, for example, the reaction of an aryl isocyanate derivative represented by general formula (2) with a pipecolic acid derivative represented by general formula (3).

Description

Description Bicyclic Hydantoin Derivatives, Process for Producing the Same, and Herbicidal Processes Containing These as Active Ingredients

The present invention relates to a novel bicyclic hydantoin derivative, a method for producing the same, an intermediate for producing the same, and a herbicide containing the bicyclic hydantoin derivative as an active ingredient. Background art

Conventionally, as bicyclic hydantoin derivatives having herbicidal activity, JP-A-60-233075 (Chem. Abs., 104: 168469z), JP-A-61 27985 (Chem. Abs., 104: 207295m), EP- Compounds described in A 0070389, DE A 3643748, EP-A-0468930, EP A 0493 323, WO-94 / 05668, WO-95 / 22547, EP A-0688773 are known. General formula of the invention (1)

There is no report on the synthesis of a derivative having a cycloalkyloxy group at the 5-position of the phenyl ring at the 3-position of the hydantoin ring as shown in the above formula.

These conventional bicyclic hydantoin derivatives have poor herbicidal effect on weeds, or those having strong activity have low safety on crops, and are not necessarily satisfactory compounds for use as herbicides. Inside The compounds listed in EP-A-0070389 or DE-A-3643748, etc., have strong herbicidal activity as shown in the test examples below, but have strong chemical harm to crops and herbicides. It is not satisfactory in terms of use as _(disclosure of the invention

The present inventors have conducted intensive studies in search of a herbicide II having excellent herbicidal activity and crop safety. As a result, before the present invention, the bicyclic hydantoin derivative represented by the general formula (1) was added to crops. The present inventors have found that they exhibit excellent herbicidal activity without application of phytotoxicity and at low doses, and have developed these simple production methods to complete the present invention.

That is, the present invention provides a compound represented by the general formula (1):

(Wherein R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl group having 1 to 4 carbon atoms).

Further, the present invention provides a compound represented by the following general formula (2):

(2)

(Wherein R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl having 1 to 4 carbon atoms.) And an aryl isocyanate derivative represented by the general formula ( 3)

(Wherein, R ¹ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.) A pipecolic acid derivative represented by the following general formula (1):

(Wherein, R represents the same meaning as described above.) A method for producing a bicyclic hydantoin derivative represented by the formula:

Further, the present invention provides a compound represented by the general formula (4):

(In the formula, R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl having 1 to 4 carbon atoms, and R ¹ represents water- It represents a rualkyl group.

Further, the present invention provides a compound represented by the general formula (1):

(The formulas B and R have the same meanings as described above.) The present invention relates to a herbicide containing, as an active ingredient, a bicyclic hydantoin derivative. BEST MODE FOR CARRYING OUT THE INVENTION

In the general formulas (1) and (2), examples of the cycloalkyl group having 5 to 6 carbon atoms represented by R include a pentyl group at a mouth and a hexyl at a mouth. Further, these substituents may be substituted by a linear or branched alkyl group having 1 to 4 carbon atoms, and specifically, a methyl group, a methyl group, a propyl group, a propyl group, an isopropyl group, and a butyl group. , Isobutyl, t-butyl and the like.

In the general formula (3), the alkyl group having 1 to 6 carbon atoms represented by R ¹ may be linear or branched, and may be a methyl group, an ethyl group, a propyl group. Groups, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, hexyl group and the like.

The arylisocyanate derivative represented by the general formula (2), which is a raw material for producing the bicyclic hydantoin derivative represented by the general formula (1) of the present invention, It can be easily produced by reacting the corresponding aniline derivative with phosgene or a phosgene equivalent in a conventional manner. The corresponding aniline derivative can be produced, for example, by the method described in EP-A-0493606, EP-A 0496347, or W0-94 / 06753, but can also be produced by the method exemplified in Reference Examples described later. .

The bicyclic hydantoin derivative of the present invention represented by the general formula (1) is, as exemplified below, an addition ring of an arylisocyanate derivative (2) and a pipecolic acid derivative (3). Can be produced by a chemical reaction.

(Wherein, R and R ¹ represent the same meaning as described above.)

In the reaction, the amino group of the pipecolic acid derivative (3) is added to the isocyanate group to form a urea derivative (4), and then the amide nitrogen and the ester are cyclized in the molecule to form a bicyclic hydantoin derivative. (1) is given. Since the cyclization reaction of the urine derivative (4) is very fast, the bicyclic hydantoin derivative (1) can be obtained in one step without isolating the urea derivative (4).

In the addition reaction between the arylisocyanate derivative (2) and the pipecolic acid derivative (3), the pipecolic acid derivative (3) itself acts as a base. Therefore, no catalyst is required, but by performing the reaction in the presence of salt 反応, the reaction rate can be increased, and π-like substances can be obtained in a short time with high yield. Examples of bases that can be used include organic amines such as triethylamine, tributylamine, N-methylmorpholine, pyridine, N, N-dimethylaniline, potassium carbonate, sodium carbonate, hydrogen hydrogen carbonate, and carbonate. Examples thereof include alkali metal bases such as sodium hydrogen, sodium hydroxide, sodium hydroxide, sodium hydride, and sodium amide. The amount of the base used is not particularly limited, and by using 0.001 to 5.0 equivalents based on the reaction mass, an H-like product can be obtained with a high yield.

This addition reaction can be carried out without a solvent, but it is preferable to use a solvent which does not harm the reaction. Solvents that can be used include, for example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene, aliphatic hydrocarbon solvents such as hexane, pentane, and heptane, getyl ether, and tetrahydrofuran. , Dioxane,

1,2-Dimethoxetane and other ether solvents; methylene chloride, chloroform, carbon tetrachloride and other halogen-based solvents; acetone, methylethylketone and other ketones; Anochol-based solvents such as methanol, ethanol, cyclohexyl alcohol, esters such as ethyl acetate and propionethyl, amides such as N, N-dimethylformamide, N-methylpyrrolidone, water and the like A mixed solvent can be exemplified.

The reaction temperature is selected from the range of −30 to 100 ° C. The urea derivative (4) is easily cyclized to give the hydantoin derivative (1), so that the urea derivative (4) can be obtained in good yield. Although it depends on the reaction conditions, it is generally preferable to carry out the reaction at a low temperature of room temperature or lower. After completion of the reaction, the desired product can be obtained by the usual isolation procedure. It can also be purified by crystallization or the like.

The cyclization reaction from the urea derivative (4) to the bicyclic hydantoin derivative (1) can be carried out under either basic or acidic conditions.

Bases that can be used in the reaction under salinity conditions include the urea derivative (4) obtained by the addition reaction of the aryl isocyanate derivative (2) and the pipecolic acid derivative (3) shown above. )) And the same bases as those exemplified in the production of). The amount of the base used is not particularly limited, and a target substance can be obtained in good yield by using 0.01 to 5.0 equivalents to the reaction substrate.

This cyclization reaction can be performed without a solvent, but it is preferable to use a solvent that does not harm the reaction. Examples of the solvent that can be used include the solvents exemplified in the addition reaction of the aryl isocyanate derivative (2) with the pipecolic acid derivative (3). The reaction temperature is selected from the range of 0 to 150 ° C, but generally the reaction can be carried out at a temperature of from room temperature to 100 ° C to obtain the desired product in good yield. After completion of the reaction, the desired product can be obtained by a usual extraction operation. However, if necessary, it can be purified by column chromatography or the like.

Examples of the acid that can be used in the reaction under acidic conditions include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as acetic acid and propionic acid.

This cyclization reaction can be carried out in a solvent that does not harm the reaction. Examples thereof include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene, and aliphatic solvents such as hexane, pentane, and heptane. Hydrocarbon solvents, ether solvents such as dimethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxetane, halogen solvents such as methylene chloride, chloroform, carbon tetrachloride, acetone, methyl ethyl ketone, etc. Use nitriles such as ketones, acetonitrile and propionitol, amides such as N, N-dimethylformamide and N-methylpyrrolidone, or water or a mixed solvent thereof. Can be.

The reaction temperature is selected within the range of 30 to 150 ° C. ffl, but it is preferable to carry out the reaction at 0 ° C. at the reflux temperature of the solvent used in terms of good yield. After completion of the reaction, the desired product can be obtained by a usual extraction operation, but if necessary, it can be purified by column chromatography or the like.

Further, the bicyclic hydantoin derivative (1) can be obtained in one step without isolating the urea derivative (4). This cycloaddition reaction can be carried out without using any catalyst: ^ The reaction can be accelerated by carrying out the reaction in the presence of a base, so that the desired product can be obtained in a short time with high yield. it can. Salts that can be used include, for example, triamines, tributylamine, N-methylmorpholine, pyridine, organic amines such as N, N-dimethylaniline, carbon dioxide lime, sodium carbonate, hydrogen carbonate lime, and the like. Examples thereof include alkali metal bases such as sodium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, and sodium amide. The amount of the base used is not particularly limited, and an H-like product can be obtained with a high yield by using 01 to 5.0 equivalents based on the reaction substrate.

This cycloaddition reaction can be performed without a solvent, but it is preferable to use a solvent that does not harm the reaction. Solvents that can be used include, for example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene, aliphatic hydrocarbon solvents such as hexane, pentane, and heptane, getyl ether, and tetrahydrofuran. , Dioxane, 1,2-dimethoxetane, etc., ether solvents, methylene chloride, chloroform, carbon tetrachloride, etc., ketones such as acetone, methylethylketone, etc., acetate nitrile, propionitol Nitriles such as ril, Esters such as ethyl acetate and ethyl propionate; amides such as N, N-dimethylformamide and N-methylpyrrolidone; and a mixed solvent thereof can be exemplified.

The reaction temperature is selected from the range of 30 to 150 ° C., but the reaction is preferably performed at 0 to 100 ° C. in terms of good yield. After the completion of the reaction, it can be purified by a column chromatography if necessary.

The compound of the present invention represented by the general formula (1) has optical isomers or isomers such as diastereomers, and is often obtained as a mixture containing all of these isomers. However, each of the isomers can be selectively synthesized using various known methods or can be separated, and the individual isomers and mixtures thereof are also included in the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto. Example

¾Example

Ethyl pipecolate (0.64 mL, 4.07 mmol) in toluene (20 mU) was stirred under ice-cooling with 4-chloro-5-cyclopentyloxy-2-fluorophenyl isocyanate (1.04 g, 4.07 g). ol) and triethylamine (0.28 mL, 2.04 ol) in toluene (10 mL) were added dropwise at 0 for 30 minutes and at room temperature for 2 hours. lo

[S] The mixture was further stirred at 80 ° C for 20 hours, and then added with acidic lithium (0.28 g, 2.04 mmol) and stirred at 100 ° C for 13 hours. After completion of the reaction, 1N hydrochloric acid (30 mL) was added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (20 <iLx2). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (80 mL), and dried over anhydrous magnesium sulfate. After filtering off the dried 剂, the filtrate is reduced tf. The crude product obtained by concentration is purified by silylation gel column chromatography (ヮ Co-gel C 200, ethyl acetate: hexane = 1: 2). Thus, 2- [4-chloro-5-cyclopentyloxy-2-fluorophenyl) 5,6,7,8 tetrahydromidazo [1,5a] pyridine-1,3 [2H, 8aH] dione (1.14 g, 76.5%) as a colorless transparent oil.

_{Ή NR (CDC1 3, TMS,} ppm): δ 1.40~1.70 (m, 5H), 1.70~2.00 (m, 7H), 2.00 ~2 · 15 (m, 1H), 2.25~2.40 (m, 1H), 2.85 to 3.00 (m, 1H), 3.96 (dd, J = 3.97 and 11.4 Hz, 1H), 4.20 to 4.35 (m, 1H), 4.70 to 4.85 (m, 1H), 6.83 (d, J _HF = 6. 49Hz, 1H), 7.25 (d, J _HF = 8.35Hz, 1H).

Ethyl pipecolate (0.31 mL, 1.99 ol) in toluene (15 m, under ice-cooling and stirring, 4-chloro-2-fluoro-5- (3-methylcyclopentyloxy) phenyl isocyanate (488 mg) , 1.81 med.) And triethylamine (0.13 mL, 0.93 mmol) in toluene (5 mL) were added dropwise at 0 ° C. for 30 minutes, followed by stirring at room temperature for 2 hours, and then potassium carbonate (126 mg, 0.91 mmol). Add Then, the mixture was stirred at 100 ° C for 5 hours. After completion of the reaction, 1N hydrochloric acid (20 mL) was added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (20 mL × 2 [Hl]). (4) The waste was combined, washed with a saturated aqueous solution of sodium chloride (50 mL), and dried over anhydrous magnesium sulfate. After filtering off the dried product, the filtrate was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (ヮ gel C200, ethyl acetate: hexane = 1: 2) to give 2 -[4-chloro-5- (3-methylcyclopentyloxy) -2-fluorophenyl] -5,6,7,8 tetrahydroidomidazo [1,5a] pyridine 1,3 [2H, 8aH] dione (611 mg, 8 8.7%) as a pale yellow oil.

_{Ή NMR (CDC1 3, TMS,} pm): δ 1.02 and 1.09 (each d, J = 6.55Hz, total 3H), 1.1 WINCH 1.22 and 1.34~1.65 (each m, total 5H), 1.75~2.18 (m, 6H ), 2.22 to 2.35 (m, 2H), 2.88 to 2.97 (m.1H), 3.96 (dd, J = 3.96 and 11.4Hz, 1H), 4.21 to 4.29 (m, 1H), 4.68 to 4.78 (m, 1H) ), 6.78 and 6.79 (each d, J _HF = 6.47 Hz, total 1H), 7.25 and 7.26 (each d, J _H F = 9.08HZ, total 1H).

Ethyl pipecolate phosphate in a 70 mL solution of 4-chloro 5-cyclopentene pentisoleoxy-2 fluorophenylisocyanate (25.6 g, 0.1 Imol) and triethylamine (0.14 mL, lmmol) under ice-cooling and stirring. (15.7 g, 0.1 Imol) was added dropwise over 30 minutes. After the dropwise addition, the mixture was stirred for 1 hour and 45 minutes while gradually raising the temperature from 0 ° C to room temperature. After the reaction, add ether (20 mL) to the reaction mixture. Hexane (70 mL) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with hexane and sufficiently dried to obtain N- [N "-(4-chloro-5-cyclopentyloxy-2-fluorophenyl) -rubumoyl] pipecolic acid ethyl ester (29.2 g). , 70.6%) as a white solid.

MP: 129-130. C

_{»H ~ NMR (CDC1 3,} TMS, ppm): δ 1.28 (t, J: 7.04Hz, 3H), 1.50~1.66Cm, 5H), 1 .69~1.96 (m, 8H), 2.26~2.34 (m , 1H), 3.29 (dt, J = 3.20 and 12.50Hz, 1H), 3.70 to 3.78 (m, 1H), 4.21 and 4.22 (each q, J = 7.11Hz, total 2H), 4.76 to 4.84 (m, 1H), 5.04 to 5.10 (m, 1H), 6.76 (brs, 1H), 7.82 (d, J „ _F = 10.60Hz, 1H), 7.95 (d, J„ _F = 7.56Hz, 1H).

MS (m / z): 412 (M ÷ .2.49), 366 (8.64), 298 (100), 271 (5.60), 235 (6.12), 187 (40.25), 158 (4.43), 84 (92.67) , 67 (7.09), 55 (16.86), 41 (23.87), 27 (5.55).

Calcd _{_{(. Calcd for C 20 H 26}} N 2 0 4 C1F)

: C, 58.18; H, 6.35; N, 6.78.

Found: C, 58.19; H, 6.39; H, 6.72¾.

Ν- [Ν '(4 Chloro-5-cyclopentyloxy 2-fluorophenyl) Power Rubamoyl] pipecolic acid ethyl ester (20.7 g, 0.05 mol), add 6N hydrochloric acid (100m or 100m or 1 hour) at 110 ° C (oil bath) After completion of the reaction, the mixture was added to the reaction mixture. Toluene (40) was added, the organic layer was separated, and the aqueous layer was extracted with toluene (40 mL × 2). Anhydrous magnesium sulfate and a small amount of activated carbon were added to the organic layer, and the mixture was dried and decolorized. By concentrating the filtrate under reduced pressure, 2- (4-chloro-5-cyclopentyloxy 2-fluorophenyl) -5,6,7,8-tetrahydromidazo [1,5-a] pyridine -1,3 [2H, 8aH] dione (16.0 g, 87.1%) was obtained as a pale brown oil. Example 1 5

Ν- [Ν '-(4-Chloro-5-cyclopentyloxy-2-fluorophenyl) Power Rubamoyl] Pipecoline Ethyl (619 mg, 1.5 mmol) and Carbonated Rime (104 mg, 0.75 iMol) in Toluene (lOmL) Was heated and stirred at 100 ° C. for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, water (10 mL) was added, organic debris was separated, and the aqueous layer was extracted with toluene (10 mL × 2). The extracts were combined, washed with saturated saline (20 mL), and dried over anhydrous magnesium sulfate. The dried product is filtered off and the filtrate is concentrated under reduced pressure. The crude product obtained is purified by silica gel column chromatography (PC-gel C-200, ethyl acetate: hexane = 1: 2). To give 2 (4-chloro-5-cyclopentyloxy-2fluorofunyl) -5,6,7,8-tetrahydroidimidazo [1,5-a] pyridine-1,3 [2H, 8aH] -dione (513 mg, 93.3%) of a colorless transparent oil was obtained. Reference Example 1

Three-separable flask equipped with a stirrer, a dropping funnel and a reflux condenser (isobutyl (5-amino-4-chloro-2-fluorophenyl) synthesized according to the method described in JP-A-4-164067). Carbonate (358 g, 1.37 mol) and toluene (750 m, then ethyl chloroformate (212 g, 1.95 mol) were added at room temperature. The reaction mixture was heated and stirred at 60 ° C to 50%. An aqueous solution of sodium hydroxide (156 g, 1.95 mol) was added dropwise over 2.5 hours, and after heating at 60 ° C. for 5 hours, tetrabutylammonium hydroxide was added to the reaction mixture. Romide (24.2 g, 0.075 mol) and cyclopentyl bromide (447 g, 3.0 mol) were added and the temperature was raised to 100 ° C. Next, sodium hydroxide aqueous solution (450 g, 4.5 mol) was added. Was added dropwise over 3.5 hours, and after the addition, the mixture was further heated and stirred at that temperature for 1 hour. Water (500 mL) was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with toluene (500 mL) .The obtained organic layers were combined, washed with water (500 mL), and toluene was distilled off under reduced pressure. Aqueous ethanol (77%, 660 mL) was added to the resulting residue to form a uniform solution by heating to TC (70 to 8), and the mixture was allowed to stand at room temperature. After washing with hydrated ethanol (75%, 500 mL) and drying thoroughly, N- (4-chloro-5-cyclopentyloxy-2-fluorophenyl) ethyl ethyl carbamate (283 g, 62.5%) was white. Crystals were obtained.

MP: 92.8-97.8. C

_{'H- NMR (CDC1 3, TMS} , ppm):. Δ 1. 33 (t, J = 7. 0Hz, 3H), 1. 40~2 10 (m, 8H), 4. 32 (q, J = 7.0 Hz, 2H), 4.88 (m, 1H), 6.87 (brs, 1H), 7.15 (d, J „ _F = 10.5 Hz, 1H), 7. 92 (d, J „ _F = 7.OHz, 1H).

IRCKBr disk, cm '): 1710, 1535, 1495, 1415, 1255. Reference example 1

A three-separable flask (3 L) equipped with a stirrer, a dropping funnel and a reflux condenser was charged with isobutyl (5-amino-4-chloro-2-fluorophenyl) carbonate (260 g, 0.99 mol), toluene (600 mL), and then chloroformic acid. Ethyl (141 g, 1.3 mol) was added at room temperature. The reaction mixture was heated and stirred at 60 ° C., and an aqueous solution of sodium hydroxide (130 g, 1.3 mol) was added dropwise over 2 hours (fjj), and the mixture was further stirred for 3 hours after the addition. The reaction was completed by adding chill (32.6 g, 0.3 mol) and an aqueous solution of 405 ° sodium hydroxide (30 g, 0.3 mol), followed by heating and stirring for 2 hours. To this was added tetrabutylammonium bromide (16 g, 0.05 mol) and cyclopentyl bromide (298 g, 2.0 mol), and the mixture was heated and stirred at 100 ° C while a 40% aqueous sodium hydroxide solution (300 g, 3. Omol) was added dropwise over 2.5 hours, and after the addition, stirring was continued at that temperature for 3 hours.After the reaction was completed, water (500 mL) was added to the reaction mixture, the organic layer was separated, and the aqueous layer was separated. The organic layers obtained were combined, washed with water (350 mL), and toluene was distilled off under reduced pressure. Was. Obtained residue in aqueous ethanol (75%, 450 mL) was added and a homogeneous solution by stirring and warmed to 70 to 80 ° C while, Leave at room temperature. The precipitated product was collected by filtration, washed with ethanol (75%, 800raL), and thoroughly dried to give ethyl (4-ethyl-5-cyclopentyloxy-2-fluorophenyl) carbamate (185g, 61. 3%) was obtained. Reference Example 1 3

A nitro flask equipped with a stirrer, a dropping funnel and an IS flow cooler (one is isobutyl (5-amino-4-chloro-2-fluorophenyl)) (131 g, 0.5 mol) and toluene (50 mL) and then ethyl chloroformate (70.5 g, 0.65 mol) were added at room temperature, and the reaction mixture was heated and stirred at 60 ° C. while 50% aqueous sodium hydroxide solution (52 g, 0.65 mol) was added. Then, the mixture was added dropwise over 5 hours, and the mixture was stirred for an additional 3 hours.Then, tetrabutylammonium bromide (8.06 g, 0.075 mol) and toluene (230 mU) were added to the reaction mixture, and 20% sodium hydroxide was added. An aqueous solution (250 g, 1.25 mol) was added dropwise over 2 hours at 80 ° C. After the addition, the mixture was heated and stirred for 8 hours, and then the reaction mixture was heated to 100 ° C. and cyclopentyl bromide (149 g, lmol) was added. Was added dropwise over 3 hours After the addition, the mixture was further heated and stirred at this temperature for 12 hours. After completion of the reaction, the toluene layer was separated, washed with water (200 mL), and toluene was distilled off under reduced pressure.To the resulting residue was added aqueous ethanol (75%, 200 mL), and the mixture was stirred. A homogeneous solution was obtained by heating to ~ 80 ° C, and the mixture was allowed to stand at room temperature.The precipitated crystals were collected by filtration, washed with aqueous ethanol (75%, 200 mL), and then dried thoroughly. By drying, white crystals of N- (4-chloro-5 cyclopentyloxy-2-fluorophenyl) ethyl ethylcarbamate (124 g, 82.3%) were obtained. Reference Example 1 4

A three-necked flask equipped with a stirrer, a dropping port and a reflux condenser (in addition, an ethyl (5-amino 4-chloro-2-fluorophenyl) carbonate synthesized according to the method exemplified in JP-A-4-164067). (119 g, 0.5 mol), toluene (250 mL), and then ethyl chloroformate (70.5 g, 0.65 mol) were added at a low temperature, and the reaction mixture was heated at 60 ° C. while stirring under 50 ° C. A sodium aqueous solution (52 g, 0.65 raol) was added dropwise over a period of 1, 25 hours, and after the addition, the mixture was further heated and stirred at 80 ° C. for 6 hours, and the reaction mixture was added to tetrabutylammonium bromide (8.lg, 0.025 mol) and cyclopentyl bromide (149 g, 1.0 mol) were added, and the mixture was heated and stirred at 100 ° C while a 40% aqueous sodium hydroxide solution (150 g,

1.5 mol) was added dropwise over 3 hours. After the addition, the mixture was further heated and stirred at that temperature for 2 hours. After completion of the reaction, water (100 mL) was added to the reaction mixture, the organic layer was separated, and water scum was extracted with toluene (100 mL). The obtained organic layers were combined and washed with water (20 OmL), and then toluene was distilled off under reduced pressure. Water-containing ethanol (75%, 200 mL) was added to the obtained residue, and the mixture was heated at 70 to 80 ° C with stirring to form a uniform solution, and left at room temperature. The precipitated product was collected by filtration, washed with hydrated ethanol (75%, 200 m), and dried thoroughly to obtain N- (4-chloro-5-cyclopentapentyloxy-2-fluorophenyl) capillate. ] 8

White crystals of ethyl ester (112 g, 74.2%) were obtained, Reference Example 1

A mixture of N- (4-chloro-5-cyclopentyloxy-2-fluorophenyl) ethyl ethyl phosphate (12.7 g, 42.lmmol), ethyl alcohol (50 mL and 2N-sodium hydroxide aqueous solution (100 mL)) The mixture was heated and stirred for 4 hours at 110 ° C. After the reaction was completed, the solvent was distilled off under reduced pressure, water (100 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The dried product was filtered off and the filtrate was concentrated under reduced pressure to give 4-chloro-5-cyclopentyloxy-2-fluoroalanine (9.36 g, 96.81) as a colorless transparent oil. I got

BP: 143 ~ 145 ° C / 1.5mmHg

'H-NMRCCDC, TMS, ppm): δ 1.40 to 2.00 (m, 8Η), 3.72 (brs, 2Η), 4.67 (m, 1 H), 6.39 (d, J _HF = 9.OHZ, lH), 7.04 (d, J „ _F = 11.0Hz, 1H).

IR (neat, cm " ¹ ): 3500, 3400, 1630, 1510, 1420, 1245, 1185. Reference Example 1 6

Trimethyl chloroformate (15 mL, 0.123 mol) in toluene (15 mL, 0.123 mol) in a 50 mU solution, 4_ chloroform 5 cyclopentyloxy-2-fluoroaniline (23.0 g, 0.1 mol) and triethylamine (0.5 mlj toluene) (The 50 ml solution was added dropwise with stirring under ice-cooling. The reaction mixture was further stirred for 1 hour under ice-cooling and then warmed to room temperature.) The resulting reaction mixture was then gasified (eg, hydrochloric acid gas and phosgene gas). The mixture was heated and stirred at 100 to 110 ° C. until the generation of water stopped.After the reaction was completed, toluene was distilled off under reduced pressure to give 4-chloro-5-cyclopentyloxy-2-fluorophenylisocyanate as a brown oil. The product was obtained almost quantitatively.

'HN RCCDCla.TMS, ppm): 31.50-2.10 (m, 8H), 4.67 (m, 1H), 6.60 (d, J _HF

= 7.5Hz, 1H), 7.12 (d, J _HF = 10.5Hz, 1H).

IR (neat, ^-'): 2275, 1720, 1615, 1525, 1470, 1195. Next, the compounds of the present invention synthesized by the methods exemplified in the above Examples are shown in Tables including the compounds shown in the Examples. Examples are shown in Table 1 and Table 1, but the present invention is not limited to these. Table 1 1 Bicyclic hydantoin-induced rest (Γ)

Compound number R ² Compound number R ²

1 H 9 3 i Pr

2 2 Me 10 2-Bu

3 3 Me 11 3 ^ Bu

4 2-Et 12 2 i Bu

5 3-Et 13 3- i -Bu

6 2 Pr 14 2- t-Bu

7 3-Pr 15 3 t-Bu

8 2-i -Pr

Table 1 2 Bicyclic hydantoin derivatives (1 ')

Compound number R ³ Compound number R ³

16 H 27 3--i -Pr

17 2-Me 28 4 i-Pr

18 3 Me 29 2 Bu

19 4-Me 30 3-Bu

20 2-Et 31 4 Bu

21 3-Et 32 2- i Bu

22 4-Et 33 3 i Bu

23 2 Pr 34 4-i Bu

24 3-Pr 35 2 t- Bu

25 4-Pr 36 3- t- Bu

26 2- i-Pr 37 4-t Bu

When the compound of the present invention is used as a herbicide, it can be used as it is, but in general, one or more adjuvants can be mixed and used as a herbicide. Usually, as an auxiliary, various carriers, extenders, solvents, surfactants, stabilizers, etc. are blended and formulated in the usual manner, for example, into wettable powders, emulsions, powders, granules, flowables, etc. To use Is preferred.

Examples of the solvent which is one of adjuvants in a herbicide containing the compound of the present invention as an active ingredient include water, alcohols, ketones, ethers, aliphatic and aromatic hydrocarbons, and halogenated hydrocarbons. , Acid amides, esters, nitriles and the like are suitable, and mixtures of these-species or two or more species are used.

Cultivation such as kaolin and bentonite; talc such as talc and limestone; mineral powders such as diatomaceous earth and oxides such as white carbon; soybean powder; and plant powders such as CMC Is used.乂、而剂剂剂よいよい剂よい乂乂乂乂乂乂乂乂乂乂乂乂. Examples of the surfactant include a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant. These surfactants are utilized as one kind or a mixture of two or more kinds depending on the use.

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, and the like, and particularly excellent effects are obtained by application at the time of germination of the control weeds before germination. be able to.

The herbicide containing the compound of the present invention as an active ingredient can be used as another active ingredient that does not inhibit the herbicidal activity of the active ingredient, such as another herbicide, an insecticide, a disinfectant, and a plant growth regulator. It is also possible to use the compounds of the present invention as active ingredients in the following preparation examples and examples of examining the herbicidal effects of the herbicides of the present invention. Explain in detail. The parts are by weight. Formulation Example 1 1 (emulsion)

An emulsion was obtained by uniformly mixing 20 parts of the compound of the present invention, 35 parts of xylene, 40 parts of cyclohexanone, and 5 parts of Solbol 900A (manufactured by Toho Chemical). Formulation Example 1 (Wetting powder)

A mixture of 50 parts of the compound of the present invention, 25 parts of algal soil, 22 parts of clay, and 3 parts of Lunox R100C (manufactured by Toho Chemical Co.) was uniformly mixed and ground to obtain a hydrate. Manufacturing example-3 (granules)

A mixture of 5 parts of the compound of the present invention, 35 parts of bentonite, 55 parts of talc, and 5 parts of lignin sodium sulfonate was uniformly mixed and pulverized, followed by adding water, kneading, and granulating with an extruder. Then, the herbicidal effect of the compound of the present invention was investigated in accordance with the method shown in Test Example 2 using a preparation prepared according to the method exemplified above. The herbicidal effect on the test weeds and the phytotoxicity on the test crops were determined according to the criteria shown in Table 13. Table 1 3 Judgment criteria

As a control compound, the following comparative drug A was used in each test, and the results are shown in the table based on the same criteria. Comparative drug A

Material) Test Example 1 1 (Effect on paddy weeds)

1 / 10,000 are pots are filled with paddy soil, and after shaving, seeds of linubie, evening magayalli, konagi, hoyurui, matsubayai, and other first-year broadleaf weeds are sown.2.5 leaves Rice (variety: Koshihikari) was transplanted and kept in harbor condition. After 1 LJ, the hydrate or emulsion of the compound of the present invention prepared according to the production example was diluted and treated so as to have a dosage of (ii) ii. The effects and phytotoxicity on rice were investigated using 1 to 5 criteria, and the results are shown in Table-4.

Table-4 Soil treatment effect before weed emergence by paddy soil

Test Example 1 (Effect of Upland Soil Treatment)

Area 10 x l0cm ^2, the field soil was filled in a back Bok depth 5 cm, this Inubi E, seeded crabgrass Aobyu, the Chenopodium album and corn seeds were covered with soil of 0. 5 cm thereon. The next day, the wettable powder or emulsion of the compound of the present invention prepared in accordance with the formulation example was diluted and uniformly spread on the covering soil so as to have a predetermined dose per are. Fifteen days after the treatment, the herbicidal effect on the test weeds and the phytotoxicity on the corn were examined using 1 to 5 criteria. Table 5 shows the results. Table 1.Soil treatment effects before weed emergence in field soil treatment

Industrial applicability

The bicyclic hydantoin derivative of the present invention has excellent herbicidal activity and high crop safety, and is useful as a herbicide. Further, these derivatives can be easily produced by the production method of the present invention via the urea derivative of the present invention.

Claims

1. General formula (1)

Request

(In the formula, R is carbon number 5 which may be substituted with an alkyl group having 1 to 4 carbon atoms.

2 of 7

Represents up to 6 cycloalkyl groups. The bicyclic hydantoin derivative represented by).

Enclosure

2. General formula (2)

(Wherein, R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl group having 1 to 4 carbon atoms.) And a general formula ( 3)

(Wherein, R ¹ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms), and is reacted with a pipecolic acid derivative which is reduced by the general formula (1):

(Wherein, R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted by an alkyl group having 1 to 4 carbon atoms.) A method for producing a bicyclic hydantoin derivative represented by the formula:

3. General formula (4)

(In the formula, R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl group having 1 to 4 carbon atoms, and R ¹ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. A urea derivative represented by).

4. General formula (1)

(Wherein, R represents a cycloalkyl group having 5 to 6 carbon atoms which may be substituted with an alkyl group having 1 to 4 carbon atoms.) A bicyclic hydantoin derivative represented by the formula: Herbicide to do.