KR930005414B1 - 1,2,4-oxadiazole derivatives and process for preparing thereof - Google Patents

Abstract

1,2,4-Oxadiazole derivs. of formula (I) are new. In (I), R1=C1-4 alkyl, allyl or benzyl; R2=C2-4 alkyl, allyl, cycloalkyl, phenyl or benzyl opt. substd. by halogen, methyl, trifluoromethyl or methoxy; R1 and R2 together form hexamethyleneamino, piperidino, pyrrolidino or morpholino with adjacent nitrogen atom; X=H, Cl, methyl, trifluoromethyl or nitro; Y=H, Cl, methyl, trifluoromethyl or methoxy; R1 and R2 together form hexamethylene amino, piperidino, pyrrolidino or morpholino with adjacent nitrogen atom; X=H, Cl, methyl, trifluoromethyl or nitro; Y=H, Cl, methyl, trifluoromethyl or methoxy; Z=H, Cl or methyl. Also claimed is the prepn. of (I) which comprises reacting a cpd. of formula (II) with phosphorus oxytrichloride, and reacting the obtd. cpd. with a hydroxyacetamide deriv. (I) are useful as herbicides.

Description

1,2,4-oxadiazole derivatives and preparation method thereof

The present invention relates to novel 1,2,4-oxadiazole derivatives useful as herbicides and methods for their preparation. The invention also relates to herbicide compositions containing such 1,2,4-oxadiazole derivatives as active ingredients.

Since 1960, various 1,2,4-oxadiazole-based compounds have been developed along with the development of organic synthesis, and have been used as medicines such as anesthetics, analgesics, or anti-inflammatory drugs by studying their biological activities.

In recent years, since it has been found that heterocyclic compounds such as thiazole, thiadiazole, isoxazole, pyrazole and the like are useful as pesticides, studies on using 1,2,4-oxadiazole compounds as pesticides have been made. It has been going on. In particular, compounds having substituted 1,2,4-oxadiazoles for amides, diphenyl ethers, sulfonyl urea compounds, etc., which are known to be effective as herbicides, have been developed, for example, in US Pat. Nos. 3,822,280 and 4,784,684, Europe Patents 0 245 818 and 0 288 275, Federal Republic of Germany Patent Publication No. 24 61 882 No. 28 43 887 and No. 31 22 340 and Japanese Patent Laying-Open No. 57-175177 and No. ) 59-36688. As described above, 1,2,4-oxadiazole-based compounds are greatly expected as herbicides, and a lot of studies are in progress.

However, in order to be an ideal herbicide, the herbicidal effect should be exerted by only one small use during the growing period of the crop, selectively herbicides on the weeds, and fundamentally no harm to the crop, Conventional herbicides have not fully met these requirements, whereas herbicides must self-decompose or dissipate in the soil so as not to contaminate it.

Accordingly, the present inventors have diligently studied to develop a herbicidal compound that satisfies the above requirements. As a result, the present inventors have introduced novel 1,2 or 4-substituted aminocarbonylmethoxy groups at the 5-position of 1,2,4-oxadiazole. , 4-oxadiazole derivatives, and strong control and herbicidal activity against blood and grass and weeds growing in the foot, in particular, the weeds have excellent control and herbicidal effect, but cultivated rice and chopped rice and corn The barley, wheat and the like are almost non-toxic and show a high selectivity between the crops and weeds, and also have a very short period of time in the soil, thus not causing problems of environmental pollution.

Therefore, the main object of the present invention is to provide 1,2,4-oxadiazole derivatives represented by the following general formula (I) useful as herbicides.

Wherein R ¹ is a C _1-4 alkyl group, an allyl group or a benzyl group, R ² is a C _2-4 alkyl group, an allyl group, a cycloalkyl group, an unsubstituted or halogen atom or a methyl, trifluoromethyl or methoxy group Or a substituted phenyl group or benzyl group, or R ¹ and R ² together with the nitrogen atom to which they are attached form a hexamethylene imino group, a piperidino group, a pyrrolidino group or a morpholino group in which an unsubstituted or alkyl group is substituted, X Is a hydrogen atom, a chlorine atom, a methyl group, a trifluoromethyl group or a nitro group, Y is a hydrogen atom, a chlorine atom, a methyl group, a trifluoromethyl group or a methoxy group, and Z is a hydrogen atom, a chlorine atom or a methyl group.

Another object of the present invention is to provide a method for preparing 1,2,4-oxadiazole derivatives of the general formula (I). Another object of the present invention is to provide a herbicide composition containing 1,2,4-oxadiazole derivatives of general formula (I).

More preferably among the compounds of the general formula (I) according to the present invention, R ¹ is a C _1-4 alkyl group or allyl group, and R ² is unsubstituted or fluorine, chlorine, methyl, wrong in the 3- or 4- position. A phenyl group substituted with a fluoromethyl or methoxy group, a C _2-4 alkyl group or an allyl group, or a piperidi in which R ¹ and R ² together with a nitrogen atom to which they are attached are hexamethylene imino groups or unsubstituted or substituted with an alkyl group Includes compounds which form a furnace group, wherein X is hydrogen, chlorine or methyl, and Y and Z are hydrogen.

Most preferred among the compounds of formula (I) according to the invention are those in which R ¹ is an isopropyl group and R ² is unsubstituted or in the 3- or 4- position fluorine, chlorine, methyl, trifluoromethyl or methoxy Or a substituted phenyl group, or R ¹ and R ² together with the nitrogen atom to which they are bonded form a hexamethyleneimino group or a piperidino group substituted with an unsubstituted or alkyl group, X is hydrogen, chlorine or methyl, Included are compounds wherein Y and Z are hydrogen.

Particularly preferred compounds are as follows.

3-phenyl-5- [N-isopropyl-N-phenyl) aminocarbonylmethoxy-1,2,4-oxadiazole, 3-phenyl-5- [N-isopropyl-N- (4′-chloro ) Phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole, 3-phenyl-5- [N-isopropyl-N- (4'-fluoro) phenyl] aminocarbonylmethoxy-1,2, 4-oxadiazole, 3-phenyl-5- [N-isopropyl-N- (4′-methyl) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole, 3-phenyl-5- [ N-isopropyl-N- (4′-methoxy) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole, 3-phenyl-5- [N-isopropyl-N- (3′-methyl ) Phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole, 3- (4'-chloro) phenyl-5- (N-isopropyl-N-phenyl) aminocarbonylmethoxy-1,2,4 -Oxadiazole, 3- (4'-methyl) phenyl-5- (N-isopropyl-N-phenyl) aminocarbonylmethoxy-1,2,4-oxadiazole, 3-phenyl-5- (2 -Ethylpiperidino) carbonylmethoxy-1,2,4-oxadiazole, and 3-phenyl-5-hexamethyleneiminocarbonylmethoxy-1,2,4-oxadiazole.

The compound of general formula (I) according to the present invention can be prepared, for example, by the following method.

Step 1:

In the above formulas, R ¹ , R ² , X, Y and Z are as defined above.

According to this method, first, according to step 1, the 5-hydroxy-1,2,4-oxadiazole derivative of the general formula (II) is reacted with phosphorus oxytrichloride, preferably in the presence of an organic base catalyst, 5-chloro-1,2,4-oxadiazole derivatives of the general formula (II) are obtained. In this reaction, pyridine or triethylamine or the like may be used in an amount of about 0.1 equivalents of the general formula (II) compound, and the reactant phosphorus oxytrichloride may be used as a reaction solvent to maintain about 106 to 48 ° C. It is preferable to carry out the reaction for 72 hours.

Then, according to step 2, the compound of the general formula (III) is reacted with the hydroxyacetamide derivative of the general formula (IV), preferably in the presence of an inorganic base catalyst to Compounds can be obtained. In this reaction, as the inorganic base, sodium hydroxide or potassium hydroxide may be used in an amount equivalent to that of the compound of the general formula (III), and a mixture of acetone and water (preferably in a ratio of 40: 1) is used as a reaction solvent. The reaction may be performed for 2 hours to 5 hours while maintaining the room temperature using 0.1 equivalent of the compound of the general formula (III) as tetraethyl ammonium chloride as a phase transfer catalyst.

The compounds of formula (II) and compounds of formula (IV) used as starting materials in the process can be purchased commercially or prepared according to known literature.

Each compound prepared above may be separated and purified according to conventional methods such as crystallization and chromatography, and the compounds were identified through IR, NMR, mass spectrometry, and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1

Step 1:

(1) Synthesis of 3-phenyl-5-hydroxy-1,2,4-oxadiazole, starting material 3-phenyl-5-hydroxy-1,2,4-oxadiazole was prepared by the following method. Synthesized accordingly.

20.6 g (0.2 mol) of benzonitrile was dissolved in 300 ml of methanol, and this solution was mixed with a solution of 14.0 g (0.2 mol) of hydroxylamine hydrochloride and 17.0 g (0.2 mol) of sodium bicarbonate in 150 ml of water. Heat reflux for 6 hours. The reaction solution obtained here was cooled to room temperature, the solvent was liberated and extracted with 500 ml of ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was again liberated. The residue was recrystallized from a mixed solvent of ether and n-hexane (3: 7) to give 25.8 g (yield: 94.9%) of pure white crystals of phenylamide oxime.

Then, 25.8 g (0.19 mole) of phenylamide oxime and 19.2 g (0.19 mole) of triethylamine were dissolved in 300 ml of methylene chloride, and 20.6 g (0.19 mole) of ethylchloroformate was added dropwise thereto. Stirred at room temperature for 1 hour. The reaction solution obtained here was washed with water (250 ml x 3), dried over anhydrous sodium sulfate, and the solvent was again liberated. The residue was recrystallized from ether to give 32.0 g (yield: 81.0%) of white crystals of 0-ethoxycarbonylphenylamide oxime.

Subsequently, 32.0 g (0.154 mol) of 0-ethoxycarbonylphenylamide oxime obtained above were added to 200 ml of a 2% aqueous sodium hydroxide solution and heated to reflux for 1 hour. The reaction solution obtained here was cooled to room temperature, neutralized with concentrated hydrochloric acid, and extracted with 250 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate to give a solvent, and then the residue was purified by column chromatography [using a mixture of ethyl acetate and n-hexane (1: 1) as eluent] to give 3-phenyl-5 as a white crystal. -Hydroxy-1,2,4-oxadiazole 19.8 (yield: 79.4%) was synthesized.

(2) Synthesis of 3-phenyl-5-chloro-1,2,4-oxadiazole

92.1 g (0.6 mole) of phosphorus oxytrichloride and 0.9 g (0.012 mole) of phosphorus oxytrichloride in 19.8 (0.12 mole) of 3-phenyl-5-hydroxy-1,2,4-oxadiazole synthesized in (1) above Were mixed and heated to reflux for 48 h. The reaction solution obtained here was cooled to 50 ° C., poured into 500 g of ice, extracted with 500 ml of ether, and the organic layer was dried over anhydrous magnesium sulfate. Solvent was advantageous, and then the residue was purified by color chromatography [using a mixture of ethyl acetate and n-hexane (1: 4) as eluent] to give 3-phenyl-5-chloro-1,2,4 as white crystals. Oxadiazole 16.2 (yield: 74.8%) was synthesized.

Melting Point: 27 ~ 28 ℃

NMR (CDCL ₃ , TMS): δ7.30 ~ 6.80 (m, 5H)

(3) Synthesis of N-methyl-N- (4′-methoxy) phenyl-α-hydroxyacetamide

Starting material, N-methyl-N- (4′-methoxy) phenyl-α-hydroxyacetamide, was synthesized according to the following method.

To 100 ml of methylene chloride, 13.6 g (0.1 mol) of N-methyl-N- (4'-methoxy) aniline and 10.1 g (0.1 mol) of triethylamine were added and stirred for 5 minutes, where α-chloroacetyl 11.3 g (0.1 mol) of ride was slowly added dropwise at 5 ° C., and then stirred at room temperature for 2 hours. The reaction solution obtained here was washed with 100 ml of water, the solvent was liberated, and the residue was recrystallized from a mixed solvent of ethyl acetate and n-hexane (1: 9) to give N-methyl-N- (4'-meth) as a white crystal. 19.9 g (yield: 93.1%) of methoxy) phenyl-α-chloroacetamide was obtained.

Then, 19.9 g (0.093 mol) of N-methyl-N- (4′-methoxy) phenyl-α-chloroacetamide obtained above and 8.2 g (0.1 mol) of sodium acetate were added to 100 ml of dimethylformaldehyde. Heat reflux for 2 hours. After cooling the reaction solution obtained, 100ml of water was added and extracted with ethyl acetate (100ml × 2). The organic layer was dried over anhydrous magnesium sulfate and the solvent was liberated. Then, 100 ml of methanol was added to the residue, and 4 g (0.1 mol) of sodium hydroxide was added thereto, followed by heating to reflux for 1 hour. Methanol was concentrated and removed from the reaction liquid obtained here, 100 ml of water was added, and it extracted with ethyl acetate (100 ml * 2). The organic layer was dried over anhydrous magnesium sulfate, the solvent was liberated, and the residue was purified by column chromatography [using a mixture of ethyl acetate and n-hexane (2: 1) as eluent] to give N-methyl as white crystals. 16.7 g (yield: 92.0%) of -N- (4'-methoxy) phenyl-α-hydroxyacetamide was synthesized.

(4) Synthesis of 3-phenyl-5 [N-methyl-N- (4′-methoxy) phenyl] -aminocarbonylmethoxy-1,2,4-oxadiazole

Dissolve 0.56 g (0.01 mol) of potassium hydroxide in 1 ml of water, where 40 ml of acetone and 0.16 g (0.001 mol) of tetraethylammonium chloride and N-methyl-N- (4'-methoxy) phenyl synthesized in (3) above were used. 1.95 g (0.01 mol) of -α-hydroxyacetamide was added and then stirred for 10 minutes. 1.80 g (0.01 mol) of 3-phenyl-5-chloro-1,2,4-oxadiazole synthesized in (2) was added to the mixture, followed by reaction at room temperature for 4 hours. Acetone was liberated from the reaction solution obtained here, and the obtained residue was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was liberated and the residue was purified by column chromatography [using a mixture of n-hexane and ethyl acetate (2: 1) as eluent] to give 3-phenyl-5- [N-methyl-N as white crystals. 2.71 g (yield: 80%) of-(4'-methoxy) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole were synthesized.

Melting Point: 128 ~ 129 ℃

NMR (CDCl ₃ , TMS): δ 8.23 ~ 6.92 (m, 9H), 4.92 (s, 2H), 3.92 (s, 2H), 4.41 (s, 3H)

[Examples 2 to 295]

In the same manner as in Example 1, to prepare a compound as disclosed in Table 1 below. Its melting point and NMR data values are shown in Table 1.

TABLE 1a

TABLE 1b

TABLE 1c

TABLE 1d

TABLE 1e

TABLE 1f

Table 1g

Table 1h

TABLE 1i

TABLE 1j

Table 1k

TABLE 1L

TABLE 1n

[Table 1m]

Table 1o

Table 1p

TABLE 1q

TABLE 1r

Table 1s

Table 1t

The herbicidal activity of the compounds of the present invention synthesized in the above examples was tested as follows.

1. Herbicide Activity Test

348 cm ² test pot was prepared, and then sterilized sand (component: clay 21%, silt 17%, sand 52%, organic matter 1.2%, pH 6.1) and horticultural complex fertilizer (N: P: K is 11:10 : Contained in a ratio of 11) in an amount of 3g per pot and put it in the test pot.

Here, sowing spheres were made, soybeans, blood, ragweed, sparrow oats, burrows, and American ginseng were sown, and then covered with finely soiled soil, and placed in a greenhouse maintained at about 25 ° C.

In the present experiment, the test compound was prepared and used as follows. In other words, 7 ml of acetone containing 0.2% of the nonionic surfactant Tween-20 (Japan Yakuri Chemical Co., Ltd.), 1.75mg (if treated at 0.5kg / ha), 3.5mg (treated at 1kg / ha) Or 14 mg (when treated at 4 kg / ha) and then mixed with 7 ml of water, used in an amount of 14 ml per 348 cm ² pot.

This is an experiment to see the effects of the test compound on the soil before germination. It is an experiment to see the effect on the first day after sowing and the leaves after germination, and 8 to 12 days after sowing. At the time, the prepared test compound was sprayed.

After spraying again in the greenhouse for 2 to 3 weeks, the herbicidal effect was examined by morphology and physiological observation conditions, and classified into 11 grades from 0 to 100 according to the criteria of Table 2 below. The results are shown in Table 3 below.

2. Herbicide Activity Assay in Fresh Water

After preparing a 140 cm ² test pot, sterilized sand (component: clay 20%, silt 18%, sand 52%, organic matter 1.6%, pH 6.2) was added to the water complex fertilizer (N: P: K = 17: 21: Contained in a ratio of 17) in an amount of 1 g per pot, pour water to make a pot and put it in the test pot. Seeds of blood and cochlea seeds were sown, two seedlings of three bases and five grains of Choi Ah-dop were sown with tweezers, and then freshwater was 3 cm deep.

Then, 1.4 mg (1 kg / ha level) of the test compound was dissolved in 2 ml of acetone containing 0.2% of the nonionic surfactant Tween-20, and then 2 ml were mixed with water, which was added in an amount of 4 ml per 140 cm ² pot. The pot was dipped into the water surface.

Pots treated with the compound were placed in a greenhouse maintained at about 25 ° C. and grown for 2 to 3 weeks, and herbicidal effects were examined by morphology and physiological observation conditions, and from 0 to 100 according to the criteria in Table 2 below. It was divided into 11 grades. The results are shown in Table 3 below.

3. Selectivity Assay for Rice and Blood

After preparing a 140 cm ² test pot, sterilized sand (component: clay 20%, silt 18%, sand 52%, organic matter 1.6%, pH 6.2) was added to the water complex fertilizer (N: P: K = 17: 21: Contained in a ratio of 17) in an amount of 1 g per pot, pour water to make a pot and put it in the test pot. The seed of blood was sown, two seedlings of three bases and five grains of Choi Ah-dop were sown with tweezers, and fresh water was 3 cm deep.

Then, 1.4 mg (1 kg / ha level) of the test compound was dissolved in 2 ml of acetone containing 0.2% of the nonionic surfactant Tween-20, and then mixed with 2 ml of water, which was added in an amount of 4 ml per 140 cm ² pot. The pot was dipped into the water surface.

Pots treated with the compound were placed in a greenhouse maintained at 25 ° C. for 2 to 3 weeks, and then herbicidal effects were examined by morphological and physiological observation conditions, and from 0 to 100 according to the criteria in Table 2 below. Graded. The results are shown in Table 4 below.

TABLE 2

Herbicide Activity Criteria

The scientific names of crops and weeds used in the above experiments are as follows, and they are abbreviated as follows in Tables 3 and 4.

TABLE 3a

Herbicide Activity Test Results

TABLE 3b

TABLE 3c

Table 3d

Table 3e

Table 3f

Table 3g

Table 3h

Note) X: Displayed when there is a suspicious result suspected of not being germinated or caused by non-chemical factors.

TABLE 4

Selectivity test results

Note> X: Displayed when suspicious results are suspected that they are not germinated or may be due to non-chemical factors.

As shown in Tables 3 and 4, the compounds of the present invention showed excellent control and herbicidal effect on blood, pollen that grows a lot in the field, and weeds. In particular, most conventional herbicides are known to harm not only weeds but also cultivated crops because most of them are not selective, but the compounds of the present invention are very safe for not only rice planting but also direct sowing rice, so that the selectivity between rice and blood is excellent.

Claims (15)

1,2,4-oxadiazole derivatives represented by the following general formula (I). Wherein R ¹ is a C _1-4 alkyl group, an allyl group or a benzyl group, and R ² is a C _2-4 alkyl group, an allyl group, a cycloalkyl group, an unsubstituted or halogen atom or a methyl, trifluoro methyl or methoxy group Or a substituted phenyl group or benzyl group, or R ¹ and R ² together with the nitrogen atom to which they are attached form a hexamethyleneimino group, an unsubstituted or alkyl group substituted piperidino group, a pyrrolidino group or a morpholino group, X Is a hydrogen atom, a chlorine atom, a methyl group, a trifluoromethyl group or a nitro group, Y is a hydrogen atom, a chlorine atom, a methyl group, a trifluoromethyl group or a methoxy group, and Z is a hydrogen atom, a chlorine atom or a methyl group. The compound of claim 1, wherein in formula (II), R ¹ is a C _1-4 alkyl group or an allyl group and R ² is unsubstituted or a fluorine, chlorine methyl, trifluoromethyl or methoxy group in the 3- or 4- position. Is a substituted phenyl group, a C _2-4 alkyl group or an allyl group, or R ¹ and R ² together with the nitrogen atom to which they are attached form a hexamethyleneimino group or an unsubstituted or alkyl substituted piperidino group, and X is A hydrogen, chlorine or methyl group and Y and Z are hydrogen. The compound of claim 1 or 2, wherein in formula (I), R ¹ is an isopropyl group and R ² is unsubstituted or a fluorine, chlorine, methyl, trifluoromethyl or methoxy group in the 3- or 4- position. Is a substituted phenyl group, or R ¹ and R ² together with the nitrogen atom to which they are attached form a hexamethyleneimino group or a piperidino group substituted with an unsubstituted or alkyl group, X is hydrogen, chlorine, or methyl, Y and Z is hydrogen. 3-phenyl-5- (N-isopropyl-N-methyl) aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- [N-isopropyl-N- (4′-chloro) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- [N-isopropyl-N- (4′-fluoro) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- [N-isopropyl-N- (4'-methyl) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- [N-isopropyl-N- (4′-methoxy) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- [N-isopropyl-N- (3'-methyl) phenyl] aminocarbonylmethoxy-1,2,4-oxadiazole. 3- (4′-chloro) phenyl-5- (N-isopropyl-N-phenyl) aminocarbonylmethoxy-1,2,4-oxadiazole. 3- (4′-methyl) phenyl-5- (N-isopropyl-N-phenyl) aminocarbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5- (2-ethylpiperidino) carbonylmethoxy-1,2,4-oxadiazole. 3-phenyl-5-hexamethyleneiminocarbonylmethoxy-1,2,4-oxadiazole. Reacting 5-hydroxy-1,2,4-oxadiazole derivatives of the general formula (II) with phosphorus oxytrichloride to yield 5-chloro-1,2,4-oxadia of the following general formula (III) After obtaining a sol derivative, the compound of formula (III) is reacted with a hydroxyacetamide derivative of formula (IV) to form 1,2,4-oxadiazole of formula (I) according to claim 1 Method of Making Derivatives. In the above formulas, R ¹ , R ² , X, Y and Z are as defined in claim 1 above. Herbicide composition containing 1,2,4-oxadiazole derivative of general formula (I) according to claim 1 as an active ingredient.