JPWO2005095335A1 - Ylide compound, its production method, herbicide and use as pharmaceutical intermediate - Google Patents

Abstract

An object of the present invention is to provide an ylide compound represented by the following general formula (1) useful as a herbicide and a method for producing the same. Still another object of the present invention is to provide a method for producing a halomethyl ketone compound known as a pharmaceutical intermediate using a compound represented by the following general formula (1). This invention solves the said subject by the novel ylide compound represented by following General formula (1), the herbicide which contains this as an active ingredient, its manufacturing method, and utilization as a pharmaceutical intermediate. [Chemical 1]

Description

  The present invention relates to a novel optically active ylide compound, a method for producing the compound, and a herbicide containing the ylide compound as an active ingredient.

  The present invention also relates to a method for producing a halomethyl ketone compound, which is a very useful intermediate of a pharmaceutical, using the ylide compound.

  Conventionally, a wide variety of herbicides have been put to practical use from her long years of research and development of herbicides, and these herbicides have contributed to labor saving in weed control work and improved crop productivity.

  Conventionally, the following method has been known as a method for synthesizing (3S) -5-halogeno-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester, which is a pharmaceutical intermediate. .

  For example, Patent Document 1 discloses a method for producing the above compound via an azo compound using (3S) -3- (N-benzyloxycarbonyl) aspartic acid β-t-butyl ester as a pharmaceutical intermediate as a raw material. It is disclosed.

  In addition, Non-Patent Document 1 discloses a method of producing via an azo compound using (3S) -3- (Nt-butoxycarbonyl) aspartic acid β-benzyl ester as a raw material.

However, these methods use diazomethane having explosive properties in the middle of the manufacturing process, and are not industrially practical.
JP-T-2002-519406 Chemical & Pharmaceutical Bulletin, 44 (11), 2037-2041 (1996)

An object of the present invention is to provide an ylide compound useful as a herbicide and a method for producing the same. Furthermore, since the compound represented by the following general formula (1) is an important intermediate for producing a halomethyl ketone compound known as a pharmaceutical intermediate, the present invention is used to obtain the efficiency of the pharmaceutical intermediate. It is an object of the present invention to provide a new and excellent manufacturing method.

As a result of intensive studies to solve such problems, the present inventors have found that the novel ylide compound represented by the above general formula (1) has low herbicidal activity and has low toxicity to human livestock and high safety in handling. I found that I have.
Further, the inventors have found a method for efficiently synthesizing a halomethyl ketone compound, which is a pharmaceutical intermediate, from the compound represented by the general formula (1), thereby completing the present invention.

That is, the present invention has the following configuration.
The first of the present invention is an optically active ylide compound represented by the above general formula (1).

(式中、Ｒ₁およびＲ₂は前記と同じ。Ｙは直鎖または分岐した炭素数1〜4のアルコキシ基、炭素数1〜4のアルキルチオ基、フェノキシ基、あるいはハロゲン原子、ニトロ基、アルキル基、アルコキシ基及びヒドロキシ基の１種以上で置換したフェノキシ基、フェニルチオ基、あるいはハロゲン原子、ニトロ基、アルキル基、アルコキシ基またはヒドロキシ基の１種以上で置換したフェニルチオ基、ベンジルオキシ基、あるいはハロゲン原子、ニトロ基、アルキル基、アルコキシ基またはヒドロキシ基の１種以上で置換したベンジルオキシ基、ベンジルチオ基、あるいはハロゲン原子、ニトロ基、アルキル基、アルコキシ基またはヒドロキシ基の１種以上で置換したベンジルチオ基、ピリジルオキシ基、ピリジルチオ基、エトキシビニルオキシ基、イミダゾリルオキシ基、アジド基、シクロへキシルカルボジイミドキシ基、スクシンイミドキシ基、フタルイミドキシ基、ベンゾトリアゾリルオキシ基、ピペリジノオキシ基、直鎖または分岐した炭素数1〜4のアルキルカルボニルオキシ基、直鎖または分岐した炭素数1〜4のアルコキシカルボニルオキシ基、置換リン酸エステル基、置換硫酸エステル基、及びハロゲン原子を表わす。)In the second aspect of the present invention, a compound represented by the following general formula (2) is reacted with trimethylsulfoxonium halide in the presence of a base to give an ylide compound represented by the following general formula (1). How to convert.

(In the formula, R ₁ and R ₂ are the same as above. Y represents a linear or branched alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, a phenoxy group, or a halogen atom, nitro group, alkyl group. A phenoxy group substituted with one or more of a group, an alkoxy group and a hydroxy group, a phenylthio group, a phenylthio group substituted with one or more of a halogen atom, a nitro group, an alkyl group, an alkoxy group or a hydroxy group, a benzyloxy group, or Substituted with one or more of a benzyloxy group, benzylthio group, or a halogen atom, nitro group, alkyl group, alkoxy group or hydroxy group substituted with one or more of a halogen atom, nitro group, alkyl group, alkoxy group or hydroxy group Benzylthio group, pyridyloxy group, pyridylthio group, ethoxyvinyloxy group An imidazolyloxy group, an azide group, a cyclohexylcarbodiimidoxy group, a succinimidoxy group, a phthalimidoxy group, a benzotriazolyloxy group, a piperidinooxy group, a linear or branched alkylcarbonyloxy group having 1 to 4 carbon atoms, a linear chain Or a branched alkoxycarbonyloxy group having 1 to 4 carbon atoms, a substituted phosphate group, a substituted sulfate group, and a halogen atom.)

The third aspect of the present invention is a method for producing a halomethyl ketone compound represented by the following general formula (3) by treating the obtained ylide compound with hydrogen halide.

  Moreover, the 4th of this invention is the herbicide which contains the compound represented by General formula (1) as an active ingredient.

When the compound of the present invention is used as a herbicide, weeding can be performed with low toxicity to human livestock and high safety in handling.
Moreover, the halomethyl ketone compound which is a pharmaceutical intermediate can be efficiently synthesized from the compound of the present invention.

式中、Ｒ₁はアミノ保護基を表し、Ｒ₂はカルボン酸保護基を表す。
具体的には、Ｒ₁はホルミル基、トリチル基、フタルイミド基、トリクロロアセチル基、トリフルオロアセチル基、クロロアセチル基、ブロモアセチル基およびヨードアセチル基、ウレタン型保護基、例えば、t−ブトキシカルボニル基、9−フルオレニルメトキシカルボニル基、ベンジルオキシカルボニル基、ベンゾイルメチルスルホニル基、ジフェニルホスフィンオキシド基などが挙げられる。
また、Ｒ₂はt−ブチル基、ベンジル基、4−ニトロベンジル基、4−メトキシベンジル基、ベンズヒドリル基、トリメチルシリル基、t−ブチルジメチルシリル基、フェナシル基、p−トルエンスルホニルエチル基、アリル基及びシンナミル基などが挙げられる。
このうち、医薬品中間体として用いる場合は、Ｒ₁がt−ブトキシカルボニル基でＲ₂がベンジル基、又はＲ₁がt−ブトキシカルボニル基でＲ₂がt−ブチル基である場合が特に好ましい。
また、化合物の例としては、Ｒ₁がt−ブトキシカルボニル基でＲ₂ がベンジル基である、(3S)-5-(1’,1’-ジメチルオキシスルフラニル)-4-オキソ-3-[カルボニル(t-ブチル)オキシアミノ]ペンタン酸 ベンジルエステル（１ａ）などがある。Hereinafter, the present invention will be described in detail.
[Ilide compounds]
The ylide compound of the present invention is represented by the following general formula (1).

In the formula, R ₁ represents an amino protecting group, and R ₂ represents a carboxylic acid protecting group.
Specifically, R ₁ is a formyl group, a trityl group, a phthalimide group, a trichloroacetyl group, a trifluoroacetyl group, a chloroacetyl group, a bromoacetyl group and an iodoacetyl group, a urethane-type protecting group such as a t-butoxycarbonyl group. , 9-fluorenylmethoxycarbonyl group, benzyloxycarbonyl group, benzoylmethylsulfonyl group, diphenylphosphine oxide group and the like.
R ₂ is t-butyl group, benzyl group, 4-nitrobenzyl group, 4-methoxybenzyl group, benzhydryl group, trimethylsilyl group, t-butyldimethylsilyl group, phenacyl group, p-toluenesulfonylethyl group, allyl group. And cinnamyl group.
Among these, when used as a pharmaceutical intermediate, it is particularly preferable that R ₁ is a t-butoxycarbonyl group and R ₂ is a benzyl group, or R ₁ is a t-butoxycarbonyl group and R ₂ is a t-butyl group.
Examples of the compound include (3S) -5- (1 ′, 1′-dimethyloxysulfuranyl) -4-oxo-3, wherein R ₁ is a t-butoxycarbonyl group and R ₂ is a benzyl group. -[Carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) and the like.

[Step of producing ylide compound]
In this step, an ylide compound is prepared by reacting the following general formula (2) with a Cory reagent (dimethylsulfoxonium methylide) synthesized from trimethylsulfoxonium halide under a basic condition in an appropriate organic solvent. (Compound (1)) can be produced. Examples of the trimethylsulfoxonium halide include bromide and iodide.
The Cory reagent can be synthesized, for example, by suspending sodium hydride in dimethyl sulfoxide, adding and dissolving methylsulfoxonium halide in small portions under a nitrogen stream, and heating to about 55 ° C.

In the formula, R ₁ and R ₂ are used in the same meaning as the above (1).
Y is substituted with one or more of linear or branched alkoxy groups having 1 to 4 carbon atoms, alkylthio groups having 1 to 4 carbon atoms, phenoxy groups, or halogen atoms, nitro groups, alkyl groups, alkoxy groups and hydroxy groups. Phenyloxy group, phenylthio group, or phenylthio group, benzyloxy group, or halogen atom, nitro group, alkyl group, alkoxy group, or hydroxy group substituted with one or more of halogen atom, nitro group, alkyl group, alkoxy group, or hydroxy group A benzyloxy group, a benzylthio group, a benzylthio group, a pyridyloxy group, a pyridylthio group, or an ethoxyvinyloxy group substituted with one or more of a halogen atom, a nitro group, an alkyl group, an alkoxy group, or a hydroxy group , Imidazolyloxy group, azide group, Cyclohexylcarbodiimidoxy group, succinimidoxy group, phthalimidoxy group, benzotriazolyloxy group, piperidinooxy group, linear or branched alkylcarbonyloxy group having 1 to 4 carbon atoms, linear or branched carbon number 1 to 4 represents an alkoxycarbonyloxy group, a substituted phosphate group, a substituted sulfate group, and a halogen atom.
Here, Y is preferably a 4-nitrophenoxy group.

  Suitable organic solvents include t-butanol, dimethyl sulfoxide, dimethylformamide, 2-methylpyrrolidinone, toluene, tetrahydrofuran, benzene, xylene, ethyl acetate, or a mixed solvent of toluene and t-butanol. Preferred solvents are 2-methylpyrrolidinone and tetrahydrofuran.

  Examples of the base include sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, potassium hydride and the like.

  The reaction temperature is -30 to 100 ° C, preferably -15 to 50 ° C. The reaction time is 10 minutes to 20 hours, preferably 30 minutes to 5 hours.

[Step of producing halomethyl ketone]
The conversion of the ylide compound (1) to the halomethyl ketone (3) is carried out in a suitable organic solvent under conditions of hydrogen halide and −50 to 100 ° C., preferably −20 to 80 ° C. ) Halomethyl ketone. Examples of the hydrogen halide include hydrofluoric acid, hydrogen fluoride, hydrochloric acid, hydrogen chloride, hydrobromic acid, and hydrogen bromide.
For example, as compound (1), (3S) -5- (1 ′, 1′-dimethyloxysulfuranyl) -4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) When (3) is used, the compound (3) includes (3S) -5-chloro-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3a ), (3S) -5- Bromo-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3b ) can be obtained.

  Suitable solvents include ethyl acetate, toluene, benzene, xylene, tetrahydrofuran, dichloroethane and the like, and the reaction time is 10 minutes to 10 hours, preferably 30 minutes to 5 hours.

  Examples of the hydrogen halide include hydrogen chloride, hydrogen bromide, hydrogen iodide, hydrogen fluoride, hydrochloric acid, hydrobromic acid, hydrofluoric acid and the like, and these may be used by dissolving in an organic solvent. Particularly preferred is hydrogen chloride or hydrogen bromide dissolved in tetrahydrofuran, or hydrochloric acid or hydrobromic acid.

[Use as herbicide]
The ylide compound represented by the above general formula (1) of the present invention (hereinafter sometimes abbreviated as “the compound of the present invention”) exhibits a reliable herbicidal effect and also exhibits selectivity between crops and weeds. Therefore, herbicides containing ylide compounds as active ingredients are suitable for controlling dicotyledonous and monocotyledonous weeds in important crops such as, for example, wheat, rice, corn, soybean, before or after germination .

  Some of the compounds of the present invention are herbicides for upland fields and non-cultivated land, and in any treatment method of soil treatment or foliage treatment, solanaceae represented by Solanum nigrum, Datura stramonium, etc. (Solanaceae) weeds, Ibibi (Abutilon theophrasti), blue-tailed deer (Malvaceae) weeds represented by Sida spinosa, Ipomoea purpurea and other morning glory (Ipomoea spps.) And convolvulus (Calystegia) Convolvulaceae weeds represented by spps., Amaranthus lividus, Amaranthus retroflexus, Amaranthaceae weeds, Xanthium orientalis, ragweed (Ambrosia artemisiaefolia), Sunflower (Helianthus annuus), yellowfin (Galinsoga ciliata), novorogi (Senecio vulgaris), himejon (Erigeron an Compositae weeds such as nus), Brassica (Rorippa indica), Noragarashi (Sinapis arvensis), Brassica weeds (Capsella bursa-pastoris), Polygonum blumei Polygonaceae weeds, such as Polygonum convolvulus, Polygonaceae weeds, Portulacaceae weeds, such as Portulaca oleracea, Chelopodium album, Chenopodium ficifolium, Butterflies (Kochia) scoparia) and other species such as red scoparia (Chenopodiaceae) weed, Stellaria media and other representative species (Caryophyllaceae) and other species, Veronica persica and other common scorpion (Scrophulariaceae) Commelina communis and other species such as Commelinaceae weed xicaule), Labiatae weeds such as Lamium purpureum, Euphorbia supina, Euphorbiamaculata weeds, Euphorbiaceae weed, Galiumurium (Rubiaceae) represented by (Rubia akane), violet (Violaceae) weed, represented by Viola mandshurica, Sesbania exaltata, Cassia obtusifolia, etc. Broad-leaved weeds such as the Leguminosae (Leguminosae) weeds, wild sorghum (Sorgham bicolor), Paccum dichotomiflorum, Johnson grass (Sorghum halepense), Echinochloa crus-galli var. Crus-galli , Echinochloa crus-galli var. Praticola, cultivated shrimp (Echinochloa utilis), bark (Digitaria adsc) endens), grass weeds (Avenafatua), canopy (Eleusineindica), green croaker (Setaria viridis), grassy weep (Alopecurus aegualis) and other species such as Graminaceous weeds (Cyperus iria), cyperus iund, cymus perus ) And other crop field weeds such as Cyperaceous weeds (Cropland weeds) have high herbicidal power.

  In addition, as a herbicide for paddy fields, both the soil treatment and the foliage treatment under submergence can be applied to the family Omodaka represented by Heramodaka (Alisma canaliculatum), Omodaka (Sagittaria trifolia), Urikawa (Sagittaria pygmaea), etc. (Alismataceae) weed, Cyperus difformis, Cyperus serotinus, Scirpus juncoides, Cyperaceae (Cyperaceae) weed represented by Cyperaceae weed, Apyna (Linder) Scrothulariaceae weed, Weeping (Potenderiaceae) weed represented by Monochoria vaginalis, etc. Rhythraceae weed, Echinochloa oryzico la), Hime Inobye (Echinochloa crus-galli var. formosensis), Inbiebi (Echinochloa crus-galli var. crus-galli) weeds, etc., and various paddy weeds (Paddy weeds) have high herbicidal power.

The application range of the herbicide of the present invention includes farmland such as upland, paddy fields, orchards, and non-agricultural land such as grounds and factory sites. The compound of the present invention can be used as a herbicide as it is, but it is formulated and used in various forms such as powders, wettable powders, granules and emulsions.
At this time, the preparation is formulated so that one or more compounds of the present invention are contained in an amount of 0.1 to 95% by weight, preferably 0.5 to 90% by weight, more preferably 2 to 70% by weight.

  Examples of carriers / diluents and surfactants used as formulation adjuvants include talc, kaolin, bentonite, diatomaceous earth, white carbon, clay and the like as solid carriers. Examples of the liquid diluent include water, xylene, toluene, acetone, chlorobenzene, cyclohexane, cyclohexanone, dimethyl sulfoxide, N, N-dimethylformamide, ethyl alcohol, 1-methylethyl alcohol and the like.

  Surfactants are preferably used depending on their effects, and examples of emulsifiers include polyoxyethylene alkylaryl ether and polyoxyethylene sorbitan monolaurate. Examples of the dispersant include lignin sulfonate and dibutyl naphthalene sulfonate. Examples of the wetting agent include alkyl sulfonates and alkyl phenyl sulfonates.

The above preparations include those that are used as they are and those that are diluted to a predetermined concentration with a diluent such as water. The concentration of the compound of the present invention when diluted is preferably in the range of 0.1 to 10%.
Moreover, the usage-amount of this invention compound is 0.01-10 kg per ha, Preferably it is 0.05-5 kg.

  The concentration and amount of use vary depending on the dosage form, use time, use method, place of use, target crop, etc., and can of course be increased or decreased without sticking to the above range. Furthermore, the compound of the present invention can be used in combination with other active ingredients such as fungicides, insecticides, acaricides and herbicides.

EXAMPLES Hereinafter, although this invention is demonstrated more concretely with a manufacture example and a test example, this invention is not limited to the following manufacture examples, unless the summary is exceeded. The NMR spectrum was measured using tetramethylsilane as an internal standard, and indicated by the next symbol or a combination thereof.
s: single line, d: double line, t: triple line, q: quadruple line, m: multiple line, bs: broad single line, dd: double double line.

[Example 1-1] Synthesis of ylide compound from 4-nitrophenyl ester (2a)
(3S) -5- (1 ′, 1′-Dimethyloxysulfuranyl) -4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a )

[Preparation of Cory reagent (dimethylsulfoxonium methylide)]
A 2000 ml four-necked flask was equipped with a stirrer (motor), a thermometer, a nitrogen introduction tube and a silica gel drying tube. Then, sodium t-butoxide (27.25 g, 0.283 mol; 2.1 eq) was added to tetrahydrofuran (room temperature) at room temperature. Suspended in 310 ml of THF). Next, 49.07 g (0.283 mol; 2.1 eq) of trimethylsulfoxonium bromide was added to the suspension at room temperature (25 ° C.) and washed with 40 ml of THF. Thereafter, the reaction solution was stirred at 50 ° C. for 1.0 h to prepare a Corey reagent. (It becomes a white suspension from gel to smooth.)

The reaction solution was cooled to −20 ° C. with a dry ice acetone bath, and (3S) -3- [carbonyl (t-butyl) oxyamino] -3-[(4′-nitrophenoxy) carbonyl] propionic acid benzyl ester ( 2a ) 60 g [Purity: 92.9 wt% (55.75 g; 0.125 mol; 1.0 eq)] was dissolved in 600 ml of THF, slowly dropped at -22 ° C to -20 ° C, and washed with 40 ml of THF. The mixture was stirred at the same temperature for about 1.5 hours, and disappearance of the raw material was confirmed by HPLC.
The reaction solution was placed in 1000 ml of ice water, and 500 ml of ethyl acetate was added for liquid separation. The aqueous layer was extracted with 350 ml of ethyl acetate, the organic layers were combined, dried over sodium sulfate, concentrated and concentrated to 52.4 g (105%) of (3S) -5- (1 ', 1'-dimethyloxysulfate) as a pale yellow oil. Furanyl) -4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) was obtained. The purity was 86.2 wt%, and when the content was determined from the purity, it was 45.19 g, and the yield was 90.9%.

[Analytical data of compound ( 1a )]
¹ H-NMR (400 MHz, CDCl ₃ ; δ, ppm):
1.44 (9H, s; C (C H ₃ ) ₃ , 2.70 (1H, dd, J = 5.8Hz, 15.9Hz: CH-C H ₂ CO, 1H), 2.93 (1H, d, J = 15.8Hz: CH -C H ₂ CO, 1H), 3.26 (3H, s: SOC H ₃ ), 3.28 (3H, s: SOC H ₃ ), 4.65 (1H, bs: NHC H CH ₂ ), 4.59 (1H, s: COC H = S), 5.11 (2H, s: Ph-C H ₂ O), 5.59 (1H, d, J = 8.7Hz: N H CH), 7.30-7.36 (5H, m: Ph- H ).
¹³ C-NMR (400 MHz, CDCl ₃ ; δ, ppm):
28.32, 37.39, 41.74, 41.94, 53.46, 66.32, 68.61, 79.53, 96.07, 128.15, 128.24, 128.27, 128.48, 155.22 (CO), 171.28 (CO), 186.41 (CO).
IR (KBr, cm ^-1 ):
3384, 3100, 3024, 2988, 2936, 1710, 1580, 1502, 1460, 1390, 1254, 1176, 1028, 944, 900, 856, 750, 682, 580, 436.
[α] _D = -29.48 ° (c 1.0, MeOH, 25 ° C)

[Example 1-2] Synthesis from succinimide ester (2b)
(3S) -5- (1 ′, 1′-Dimethyloxysulfuranyl) -4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a )

Preparation of Corey reagent (dimethylsulfoxonium methylide)
A 300 ml four-necked flask was equipped with a stirrer (motor), thermometer, nitrogen inlet tube and silica gel drying tube, and then 2.52 g (0.0262 mol; 2.2 eq) of sodium t-butoxide was added to toluene / t-butanol = 10 at room temperature. / 1 The suspension was 110 ml, and trimethylsulfoxonium bromide 4.54 g (0.0262 mol; 2.2 eq) was added at room temperature (22 ° C.), followed by washing with 10 ml of the above solvent. Thereafter, the reaction solution was stirred at 50 ° C. for 1.0 h to prepare a Corey reagent. (It became a white suspension from gel to smooth.)

The reaction solution was cooled to −20 ° C. with a dry ice acetone bath, and 5 g of (3S) -3- [carbonyl (t-butyl) oxyamino] -3-[(succinimidoxy) carbonyl] propionic acid benzyl ester ( 2b ) (0.0119 mol; 1.0 eq) was added as a solid at -22 ° C to -20 ° C and washed with 5 ml of the above solvent. The mixture was stirred at the same temperature for 2 hours, and disappearance of raw materials was confirmed by HPLC.
The reaction solution was placed in 200 ml of ice water, and 100 ml of ethyl acetate was added for liquid separation. The aqueous layer was extracted with 100 ml of ethyl acetate, and the organic layers were combined, dried over anhydrous sodium sulfate and concentrated to 4.79 g of (3S) -5- (1 ', 1'-dimethyloxysulfuranyl)- 4-Oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) was obtained. The purity was 76.8 wt%, and when the content was determined from the purity, it was 3.68 g, and the yield was 77.8%.
Analytical data was the same as in Example 1-1.

[Example 2-1] Synthesis using ylide derived from nitroester
(3S) -5-Chloro-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3a )

After adding a stirrer (motor), thermometer and silica gel drying tube to a 500 ml four-necked flask, (3S) -5- (1 ', 1'-dimethyloxysulfuranyl) -4-oxo-3- [ Carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) [purity 83.6 wt% 6.76 g [18 mmol; purity conversion, 5.65 g (14.2 mmol)]) was dissolved in THF 135 ml and concentrated hydrochloric acid 1.18 ml (14.2 mmol) ; 1.0 eq) was added. The mixture was heated to 50 ° C. in a water bath, and the raw material disappeared in 1.5 hours. The THF solvent was concentrated about 90%, and the residue was poured into 200 ml of ice water. Precipitated white crystals were filtered off, washed well with water and dried to give 4.99 g (82.51%) of white crystals of (3S) -5-chloro-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid The benzyl ester ( 3a ) was obtained. HPLC measurement showed 85.51 area%. The purity was 91.21 wt%, and when the content was determined from the purity, it was 4.55 g, and the yield was 90.0%.

[Analytical data of compound ( 3a )]
¹ H-NMR (400 MHz, CDCl ₃ ; δ, ppm):
1.46 (9H, s; C (C H ₃ ) ₃ , 2.86 (1H, dd, J = 4.9Hz, 17.3Hz: CH-C H ₂ CO, 1H), 3.09 (1H, d, J = 17.3Hz: CH -C H ₂ CO, 1H), 4.40 (2H, dd, J = 16.1Hz: COC H ₂ Cl), 4.64 (1H, bs: NHC H CH ₂ ), 5.12 (2H, s: Ph-C H ₂ O ), 5.52 (1H, d,: N H CH), 7.32-7.38 (5H, m: Ph- H ).
¹³ C-NMR (400 MHz, CDCl ₃ ; δ, ppm):
28.27, 35.82, 46.95, 54.28, 67.15, 80.10, 96.14, 128.30, 128.55, 128.68, 135.12, 155.23 (CO), 171.21 (CO), 200.32 (CO).
IR (KBr, cm ^-1 ):
3364, 2988, 2948, 1742, 1682, 1522, 1462, 1414, 1392, 1374, 1304, 1256,1218, 1192, 1164, 1114, 1054, 1028, 992, 982, 912, 860, 782, 752, 700, 654, 580, 526, 472.
mp76-78 ℃
[α] _D = -64.68 ° (c 1.0, MeOH, 25 ° C), chiral HPLC; 99.5% ee

[Example 2-2] Synthesis using ylide derived from imide ester
(3S) -5-Chloro-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3a )
After adding a stirrer (motor), thermometer and silica gel drying tube to a 500 ml four-necked flask, (3S) -5- (1 ', 1'-dimethyloxysulfuranyl) -4-oxo-3- [ Carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) [purity 87.4 wt% 4.35 g [10.9 mmol; converted to purity, 3.36 g (8.5 mmol)] was dissolved in 90 ml of THF, and 0.71 ml (8.5 mmol) of concentrated hydrochloric acid was dissolved. ; 1.0 eq) was added. The mixture was heated to 50 ° C. in a water bath, and the raw material disappeared in 1.5 hours. The THF solvent was concentrated and the residue was poured into 200 ml of ice water. The precipitated white crystals were separated by filtration, washed well with water and dried, and 3.53 g of white crystals (3S) -5-chloro-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3a ) HPLC measurement showed 91.84 area%. The purity was 74.6 wt%, and when the content was determined from the purity, it was 2.64 g, and the yield was 87.5%.

[Analytical data of compound ( 3a ) derived from imidoester ( 2b )]
mp 71-74 ℃
[α] _D = -57.7 ° (c 1.0, MeOH), chiral HPLC; 99.5% ee
Analysis data other than the above was the same as in Example 2-1.

[Example 3-1] Synthesis using ylide derived from nitroester

(3S) -5-Bromo-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3b )

After attaching a stirrer (motor), a thermometer and a silica gel drying tube to a 1000 ml four-necked flask, (3S) -5- (1 ′, 1′-dimethyloxysulfuranyl) -4-oxo-3- [ Carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester (1a) 25.0g [purity 86.2wt%; 21.6g (0.0543mol: 1.0eq)] dissolved in 500ml THF, 48% hydrobromic acid aqueous solution at 15 ° C 9.15 g (0.543 mol; 1.0 eq) was added dropwise. The reaction solution turned from pale yellow to colorless. The mixture was heated to 50 ° C. in a water bath, and the raw material disappeared in 1.5 hours. Some insolubles were filtered off, the THF solvent was concentrated, the concentrate was poured into 500 ml of ice water and washed with 10 ml of THF. The precipitated white crystals were separated by filtration, washed well with water and dried, and 20.8 g (82.8%) of white crystals (3S) -5-bromo-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid The benzyl ester ( 3b ) was obtained. HPLC measurement showed 83.0 area%. The purity was 90.07 wt%. When the content was determined from the purity, it was 18.78 g, and the yield was 86.56%.

[Analytical data of compound ( 3b )]
¹ H-NMR (400 MHz, CDCl ₃ ; δ, ppm):
1.46 (9H, s; C (C H ₃ ) ₃ , 2.87 (1H, dd, J = 4.8Hz, 17.3Hz: CH-C H ₂ CO, 1H), 3.07 (1H, dd, J = 4.8Hz, 17.3 Hz: CH-C H ₂ CO, 1H), 4.18 (2H, s,: COC H ₂ Cl), 4.72 (1H, bs: NHC H CH ₂ ), 5.12 (2H, s: Ph-C H ₂ O) , 5.60 (1H, d,: N H CH), 7.26-7.41 (5H, m: Ph- H ).
¹³ C-NMR (400 MHz, CDCl ₃ ; δ, ppm):
28.25, 32.36, 35.85, 54.08, 67.07, 80.85, 128.26, 128.50, 135.14, 155.23 (CO), 171.21 (CO), 200.32 (CO).
IR (KBr, cm ^-1 ):
3360, 2988, 2952, 1742, 1680, 1522, 1464, 1414, 1392, 1374, 1364, 1300,1250, 1218, 1192, 1154, 1108, 1052, 1032, 980, 946, 912, 860, 784, 752, 700, 664, 646, 578, 518, 466, 430
mp 68-70 ℃
[α] _D = -73.73 ° (c1.0, MeOH)

[Example 3-2] Synthesis using an ylide derived from an imide ester
(3S) -5-Bromo-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 3b )
A 200 ml 4-neck flask was equipped with a stirrer (motor), thermometer, and silica gel drying tube, and then (3S) -5- (1 ', 1'-dimethyloxysulfuranyl) -4-oxo-3- [Carbonyl (t-butyl) oxyamino] pentanoic acid benzyl ester ( 1a ) 4.67g [purity 76.8wt%; 3.59g (0.0095mol: 1.0eq)] dissolved in 90ml THF, 48% hydrobromic acid at 21 ° C The solution was heated to 50 ° C. in a water bath in which 1.60 g (0.0095 mol; 1.0 eq) of an aqueous solution was added dropwise, and since the raw material disappeared in 1.5 h, the heating was stopped in 2.0 h and the mixture was cooled. Some insolubles were removed by filtration, the THF solvent was concentrated, and the mixture was poured into 200 ml of ice water as 4.9 g and washed with 5 ml of THF. The precipitated white crystals were separated by filtration, washed well with water and dried, and 3.59 g (94.8%) of white crystals (3S) -5-bromo-4-oxo-3- [carbonyl (t-butyl) oxyamino] pentanoic acid The benzyl ester ( 3b ) was obtained. HPLC measurement showed 91.3 area%. The purity was 93.1 wt%, and when the content was determined from the purity, it was 3.34 g and the yield was 88.3%.

[Analytical data of compound ( 3b ) derived from imide ester ( 2b )]
mp 73-75 ℃
[α] _D = -75.32 ° (c1.0, MeOH)
Analysis data other than the above was the same as in Example 3-1.

  Next, formulation examples and test examples will be shown. Carriers (diluents) and auxiliaries, their mixing ratios and active ingredients can be varied within a wide range. “Parts” in each formulation example represents parts by weight.

[Formulation Example 1 (wettable powder)]
The following ingredients are mixed and ground to make a wettable powder, diluted with water and used.
Irido compound ( 1a ) 50 parts White carbon 10 parts Sodium lignin sulfonate 5 parts Sodium alkyl sulfonate 3 parts Diatomaceous earth 32 parts

[Production Example 2 (emulsion)]
The following ingredients are uniformly mixed to give an emulsion, which is diluted with water and used.
Ylide compound ( 1a ) 25 parts xylene 65 parts polyoxyethylene alkylaryl ether 10 parts

[Production Example 3 (Granule)]
The following components are uniformly mixed, water is further added and kneaded, and the mixture is granulated with an extrusion granulator and used as a granule.
Ylide compound ( 1a ) 8 parts Bentonite 40 parts Clay 45 parts Calcium lignin sulfonate 7 parts

[Test Example 1]
Herbicidal activity test of the ylide compound of the present invention (1) The germination inhibitory effect was examined on the following five types of plants.
(I) Amaranthus retroflexus
(B) Lettuce (Asteraceae) Lactuca sativa
(C) Dogwood (Solanum) Solanum nigrum
(D) Kogomekatsukiri (Spiritaceae) Cyperus iria
(E) Enokorogusa (Poaceae) Setaria viridis

(2) Test method Seeds were treated with 1% sodium hypochlorite solution for 2 minutes, then washed with sterilized water and air-dried. One filter paper (21 mm diameter for Kiriyama funnel) was spread on a 12-hole microplate, and seeds were sown.
0.3 ml of chemical solution was dispensed into a microplate with 2-fold diluted Murashige-Skoog salts (MS), covered with cellophane tape, and then kept in a temperature control chamber.

(3) Investigation method After cultivation for a predetermined period, the effect on the foliage and roots was objectively evaluated.
The effect index and symptoms are shown in Table 1.
Days until investigation and culture temperature: 7 days, 25 ° C, 4000-5000 lx (24-hour lighting conditions)

According to the present invention, the herbicide containing the compound represented by the general formula (1) as an active ingredient can perform herbicidal action with low toxicity to human livestock and high safety in handling.
Moreover, the efficient manufacturing method of the halomethyl ketone compound which is a pharmaceutical intermediate can be provided using the compound of this invention.

Claims (5)

An optically active ylide compound represented by the following general formula (1).

A process for producing an ylide compound represented by the following general formula (1) by reacting a compound represented by the following general formula (2) with trimethylsulfoxonium halide in the presence of a base.

(In the formula, R ₁ and R ₂ are the same as above. Y represents a linear or branched alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, a phenoxy group, a halogen atom, a nitro group, A phenoxy group substituted with one or more of an alkyl group, an alkoxy group and a hydroxy group, a phenylthio group, or a phenylthio group substituted with one or more of a halogen atom, a nitro group, an alkyl group, an alkoxy group or a hydroxy group, a benzyloxy group, Or substituted with one or more of a halogen atom, nitro group, alkyl group, alkoxy group or hydroxy group, substituted with one or more of a benzyloxy group, benzylthio group, or halogen atom, nitro group, alkyl group, alkoxy group or hydroxy group Benzylthio group, pyridyloxy group, pyridylthio group, ethoxyvinyloxy Imidazolyloxy group, azido group, cyclohexylcarbodiimidoxy group, succinimidoxy group, phthalimidoxy group, benzotriazolyloxy group, piperidinooxy group, linear or branched alkylcarbonyloxy group having 1 to 4 carbon atoms, direct (Represents a chain or branched C 1-4 alkoxycarbonyloxy group, substituted phosphate group, substituted sulfate group, and halogen atom.)

A process for producing an halomethyl ketone compound represented by the following general formula (3) by reacting an ylide compound represented by the following general formula (1) with a hydrogen halide in an inert solvent.

A herbicide containing a compound represented by the following general formula (1) as an active ingredient.

Use of an ylide compound represented by the following general formula (1) for producing a halomethyl ketone compound represented by the following general formula (3).