KR960012194B1 - Novel heteroaryliminoester derivative of 6-chloro-2-(4,6-dimetoxy pyrimidine-2-yl)oxybenzoic acid and process for preparation thereof - Google Patents

Abstract

The heteroaryliminoester derivatives of formula(I) useful as a herbicide are prepared by reacting compd. of formula(II) with compd. of formula(III) in the presence of metal salt such as CuBr2 or CuCl2. In formula, Q is pyridine, furan, methylfuran, benzofuran, dimethylfuran, thiophene, chlorothiophene, methylthiophene, methylpyrrol; R is methyl, chloride, methoxy, methylthio, methoxy carbonyl group.

Description

Heteroarylimino ester derivatives of novel 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid and preparation method thereof

The present invention relates to novel herbicidal pyrimidine derivatives represented by the following general formula (I), more particularly heteroaryl of 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid Imino ester derivatives, methods for their preparation and their use for combating plants harmful to crops.

Wherein Q represents a hetero aryl group; R is a straight-chain, branched or cycloalkyl group having 1 to 4 carbon atoms or a saturated or unsaturated bond, halogen atom, C ₁ -C ₄ alkoxy group, C ₁ -C ₄ alkylthio group, phenyloxy group, phenylthio group, alkoxycarbonyl group Or a nitrile group.

In the substituent definition of the general formula (I), examples of preferred alkyl groups include methyl, ethyl, vinyl, propyl, isopropyl, allyl, n-butyl, sec-butyl, isobutyl, cyclopropyl group, and most preferably methyl , Ethyl, propyl or isopropyl groups.

Examples of preferred alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, allyloxy, n-butoxy, sec-butoxy, t-butoxy, isobutoxy group and the like, most preferably methoxy, Oxy, propoxy or isopropoxy groups.

Examples of preferred alkylthio groups are methylthio, ethylthio, propylthio, isopropylthio, allylthio, n-butylthio, sec-butylthio, isobutylthio group, and the like, most preferably methylthio or ethylthio group. .

In addition, heteroaryl refers to a 5-6 membered aromatic hydrocarbon compound containing at least one hetero atom such as oxygen, nitrogen, or sulfur in the ring, and preferred examples thereof include pyridine group, furan group, thiophene group, and pyrrole group. Etc.

In the compound according to the present invention, syn-isomers and anti-isomers may exist respectively or together around imino groups in the structure of Formula (I). All such isomers are included in the scope of the present invention.

It is already well known that 2-phenoxypyrimidine or (pyrimidin-2-yl) oxybenzene derivatives are useful as herbicides (Agr. Biol. Chem., Vol. 30, P.896 (1966) and Japanese patents). See publication 54-55729). Of the compounds recently developed based on 2-phenoxypyrimidine, it has been found that derivatives of 2- (pyrimidin-2-yl) oxybenzoic acid show excellent herbicidal effects (e.g., Europe Patent applications 223,406, 249,708, 287,072, 287,079, 315,889, 321,846, 330,990, 335,409, 346,789, 363,040, 402,751, 435,170, 435,186, 457,505, 459,243, 468,690, British Patent No. 2,237,570 and German Patent Application No. 3,942,476). These known compounds show a similar mechanism of action to sulfonylurea derivatives, imidazolinol derivatives, and triazolepyrimidine derivatives, which are well known as conventional amino acid biosynthesis inhibitors, and have the advantage of simplicity due to their simple structure. There is a growing interest as a herbicide with a novel structure of amino acid biosynthesis.

Their herbicidal action mechanism mediates the process of making acetolactate, which is the first step in biosynthesis, in which plants make essential amino acids, such as valine and isoleucine, from pyruvic acid. It is known to inhibit the activity of acetolactate synthase called ALS (Acetolatate Synthase).

Of these known compounds, ester derivatives of 2- (pyrimidin-2-yl) oxybenzoic acid have little herbicidal effect on their own, but are hydrolyzed by esterase in the plant and thus, the herbicidal active substance 2- ( A herbicide pro-herbicide, which is converted to pyrimidin-2-yl) oxybenzoic acid and exhibits herbicidal efficacy, is an enzyme activity assay using ALS enzyme (Pestic. Sci., Vol. 31, P305 (1991)). Is known as

Contrary to this report, the inventors of the biosynthesis inhibition assay using the ALS enzyme showed that, among the ester derivatives of 2- (pyrimidin-2-yl) oxybenzoic acid, certain types of ester derivatives are excellent in themselves. It has also been found to have an inhibitory effect, and among these ester derivatives, in particular imino ester derivatives, to have excellent herbicidal activity. Therefore, the compounds presented in the present invention do not have the concept of herbicide precursors, but have excellent ability to inhibit ALS enzymes by themselves. The imino ester derivatives of the present invention have much superior herbicidal power than other known ester derivatives, and also have high selectivity for crops.

The present invention provides a heteroarylimino ester derivative of novel 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid represented by the following general formula (I).

Wherein Q and R are as described above, respectively.

It is an important feature that the compound of general formula (I) according to the present invention comprises a heteroarylimino ester of 6-chloro-2- (pyrimidin-2-yl) oxybenzoic acid.

Generally, in order for 2- (pyrimidin-2-yl) oxybenzoic acid derivatives to show stronger herbicidal efficacy, substituents (particularly chloro) are required at the 6-position of the benzene ring of benzoic acid. In this case, however, the synthesis of imino ester derivatives becomes a problem due to its structural characteristics. Therefore, it is known that the imino ester derivatives of general 2- (pyrimidin-2-yl) oxybenzoic acid are free of substituents at the 6-position. For example, EP 346,789 only describes simple imino ester derivatives using oximes made from acetone, cyclohexyl, cyclopentyl and the like, but has no mention of synthetic methods or weed control effects.

Moreover, there are no reported examples of imino ester compounds having heteroaromatic rings, such as the heteroarylimino ester compounds presented in the present invention.

In addition, generally known synthetic methods cannot synthesize the imino ester compounds of the present invention, and in special cases, they are synthesized in extremely low yields (less than 5%).

Compounds in which the '2,6' position of the benzoic acid is substituted like the general formula (I) in the present invention are steeply steeply hidden in the carboxylic acid group. Therefore, these iminooxy ester derivatives cannot be synthesized in high yield according to conventional methods (Tetrahedron, Vol. 36, P 2409 (1980), J. Org. Chem., Vol. 35, 1198 (1970)). Moreover, the esterification reaction of benzoic acid in the case of steric hindrance is generally not very useful for the synthesis of the compound of the present invention because of strong acidic conditions.

In order to overcome this point, the compound (I) of the present invention utilizes a pyridine mercapto ester represented by the following general formula (II) as an important intermediate.

The pyridine mercapto ester compound represented by the general formula (II) is useful not only for synthesizing the novel iminooxy ester compound of the present invention but also for synthesizing most ester compounds that are difficult to synthesize by a general method. Do.

The compound of formula (I) according to the present invention is reacted by reacting a compound of formula (II) and a compound of formula (III) in the presence of a solvent or a metal salt or in the absence of a metal salt according to the following scheme (A) It can manufacture.

Scheme (A)

Wherein Q and R are as described above, respectively.

The reaction according to Scheme (A) may be performed at high temperature or room temperature. In the case of room temperature reaction, it is preferable to react in the presence of a metal salt. In this case, halogenated hydrocarbons such as CH ₂ Cl ₂ , CHCl ₃ , CCl ₄ , CH ₂ ClCH ₂ Cl, or CH ₃ CN, CH ₃ CH ₂ CN, etc. may be used. It is desirable to. The metal salt is preferably a copper (II) salt such as CuBr ₂ or CuCl ₂ .

On the other hand, when the reaction is carried out at a high temperature, it is not necessary to use a metal salt, but it is particularly preferable to react at a reflux temperature of the solvent using a solvent having a high boiling point such as xylene.

Compounds of the general formula (III) used in the above scheme (A) are easily synthesized by reacting hydroxylamine from aldehyde compounds (IV) which are generally known according to the following scheme (B), for example.

Scheme (B)

Wherein Q is as defined above and R represents an alkyl group or an alkoxycarbonyl group.

Alternatively, a compound of the general formula (III) can be synthesized from the generally known oxime compound (V) according to the following reaction scheme (C).

Scheme (C)

Wherein Q is as described above and R represents an alkoxy group, an alkylthio group, a phenyloxy group or a phenylthio group.

In addition, the pyrimidine mercapto ester compound of formula (II), for example, is known from the known 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid as the trialkyl or triphenylphosphate. Prepared by reacting with 2,2'-dipyridyldisulfide or 4,4'-dipyridyldisulfide in the presence of fins and solvents, wherein as solvent acetone, toluene, benzene, ether, ethyl acetate, CH ₂ Cl ₂ CHCl ₃ , CH ₂ ClCH ₂ Cl and the like can be used (see Korean Patent Application No. 93-1017, filed on January 27, 1993).

Representative of the heteroarylimino ester derivatives of the novel 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid represented by the general formula (I) prepared according to the method of the present invention. Examples are shown in Table 1 below. Since syn-isomers and anti-isomers may exist respectively or together around imino groups, all of these isomers are included in the scope of the present invention.

Table # 1

Compounds (I) of the present invention are superior to the known derivatives of 6-chloro-2- (pyrimidin-2-yl) oxybenzoic acid by pollen, weed and broadleaf weed or annual weed and perennial weed. In addition to being effective, it has been found to be a good herbicide that does not manifest cotton and rice damage in control of their weeds.

In addition, since the compound of the general formula (I) of the present invention has a heteroarylimino structure, we have excellent control effect not only in soil treatment but also foliage treatment during weed control.

Therefore, the heteroarylimino ester derivative of the general formula (I) according to the present invention exhibits high active herbicidal power for cultivated crops under field conditions or paddy conditions, and is particularly useful for combating harmful plants in cotton growing areas.

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

However, these examples are only for the understanding of the present invention, and the scope of the present invention is not limited thereto.

Preparation Example 1 Synthesis of Oxime (III-3) (Q = 2-methyl-5-furan, R = CH ₃ )

By reaction scheme (B), 12.4 g of 2-acetyl-5-methylfuran, 7.0 g of hydroxylamine hydrochloride, and 14.0 g of potassium carbonate were added to 200 ml of methanol and stirred at room temperature for 5 hours. After the reaction mixture was filtered, methanol was distilled off under reduced pressure to obtain 14.0 g (yield 99%) of the title compound (III-3) as a white solid.

Oxime compound (III-1) (Q = 3-pyrimidine, R = CH ₃ ), (III-2) (Q = 2-furan, R = CH ₃ ), (III-8) (Q = 2-benzofuran, R = CH ₃ ), (III-9) (Q = 2,5-dimethyl-3-furan), (III-10) (Q = 2-furan, R = COOCH ₃ ,), ( III-11) (Q = 2-thiophene, R = CH ₃ ), (III-13) (Q = 3-thiophene, R = CH ₃ ), (III-14) (Q = 2-thiophene, R = COOCH ₃ ), (III-15) (Q = 3-thiophene, R = COOCH ₃ ), (III-16) (Q = 2-chloro-5-thiophene, R = CH ₃ ), (III (18) (Q = 3-methyl-2-thiophene, R = CH ₃ ), (III-19) (Q = 5-methyl-2-thiophene, R = CH ₃ ), (III-20) ( Q = 2,5-dimethyl-3-thiophene, R = CH ₃ ), (III-22) (Q = N-methyl-3-pyrrole, R = CH ₃ ) were readily synthesized from ketone compound (IV). .

Preparation Example 2 Synthesis of Oxime (III-4) (Q = 2-methyl-5-furan, R = Cl)

According to the method of Scheme (C), 12.5 g of oxime compound of 2-methyl-5-furanaldehyde and 13.4 g of N-chlorosuccinimide were added to 200 ml of dichloromethane and stirred under reflux for 3 hours. After the reaction mixture was filtered, the solvent was distilled under reduced pressure, and the residue was chromatographed on silica gel to obtain 11.2 g (yield 80%) of the title compound (III-4).

Preparation Example 3 Synthesis of Oxime (III-5) (Q = 2-methyl-5-furan, R = SCH ₃ )

14.0 g of the oxime compound (III-4) synthesized in Preparation Example 2 was dissolved in 100 ml of tetrahydrofuran, and 7.1 g of sodium diomethide was slowly added dropwise for 5 minutes while stirring. After 1 hour, 100 ml of saturated ammonium chloride solution is added and extracted with 200 ml of ethyl acetate. The extract was dried over anhydrous forget-me-not, the solvent was distilled under reduced pressure, and the residue was chromatographed on silica gel to obtain 14.0 g (yield 95%) of the title compound (III-5). In the same manner, oxime compound (III-6) (Q = 2-methyl-5-furan, R = OCH ₃ ), (III-7) (Q = 2-methyl-5-furan, R = OCH ₃ ), ( III-21) (Q = 5-methyl-2-thiophene, R = SCH ₃ ) was synthesized.

Preparation Example 4 Synthesis of 2-pyridinethio ester (II) of 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid

31.0 g of 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid, a known compound, 22.0 g of 2.2'-dipyridyldisulfide and 26.2 g of triphenylphosphine were toluene Put in 250ml and vigorously stirred at room temperature for 3 hours. The reaction mixture is filtered and distilled under reduced pressure to remove toluene. The residue was chromatographed on silica gel to give 36.3 g (yield: 90%) of the title compound (II) as a white solid.

'H NMR (CDCI ₃ δ), 3.826 (6H, s), 5.794 (1H, s), 7.184 (1H, d), 7.3 to 7.4 (3H, m), 7.74 (2H, d), 8.60 (1H, d).

Example 1

Compound (5) (Q = 2-methyl-5-furan, R = SCH ₃ )

1.4 g of oxime (III-5) synthesized in Preparation Example 3 and 4.0 g of thioester compound (II) synthesized in Preparation Example 4 were dissolved in 50 ml of CH ₂ Cl ₂ . After stirring the reaction solution at room temperature, 2.2 g of CuBr ₂ was added, followed by further stirring for 1 hour. The reaction mixture was filtered and the residue distilled under reduced pressure was chromatographed on silica gel to obtain 3.7 g (yield: 90%) of the title compound (1).

Example 2

Synthesis of compound (11) (Q = 2-thiophene, R = CH ₃ , Syn) with compound (12) (Q = 2-thiophene, R = CH ₃ , anti)

1.4 g of oxime (III-11) synthesized in Preparation Example 1 and 4.0 g of thioester compound (II) synthesized in Preparation Example 4 were dissolved in 50 ml of dichloromethane, followed by stirring at room temperature. After 5 minutes, 2.2 g of CuBr ₂ was added, followed by further stirring for 1 hour. The reaction mixture was concentrated by filtration and chromatography on silica gel to give 3.0 g (yield: 80%) of the title compound (11) and 0.7 g (18% yield) of the title compound (12).

Compounds (1) to (23) shown in Table 1) can be synthesized in the same manner as in Example 1 or Example 2.

Physical properties of the synthesized compounds are shown in Table 2).

Table # 2

The herbicidal efficacy of the phenylimino ester derivative of the novel herbicidal 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid represented by the general formula (I) according to the present invention In order to test, potted plants were tested in pots for pot cultivation and treatment, and efficacy evaluation was carried out according to the evaluation criteria of efficacy and weakness (Table 3).

For the efficacy test, field weeds were Digitaria sanguinalis, Sataria farberi, Echinochgloa crus-galli var.caudata, Sorghum bicolor, Aeschynomene indica, Solanum migrum, Gosshipium hirsutum was selected for crops with Abutilon theophrasti and Calystegia japonica.

When the compound (I) of the present invention is used, it is mixed with solid materials such as clay, talc and diatomaceous earth and liquid materials such as water, alcohol, benzene, toluene, ether, ketones, esters, acids and amides, and the like. It can be prepared and used in any formulation such as powder, granule, and the like, and an emulsifier, a dispersant, a penetrant, an electrodeposition agent, and a stabilizer are added as necessary.

Some examples of the formulation of the herbicide containing the compound of the present invention as an active ingredient are shown below, but the technical scope of the present invention should not be limited by this method.

Formulation Example 1): (field conditions, 16 g / ha)

5 mg of the compound of the present invention was dissolved in 640 ml of an organic solvent (acetone), and then diluted in 640 ml of distilled water containing 0.2% of the nonionic surfactant Tween 20 to prepare a blend.

Formulation Example 2): (Pawing Conditions, 16g / ha)

5 mg of the compound of the present invention was dissolved in 320 ml of an organic solvent (acetone), and then diluted in 320 ml of distilled water containing 0.2% of the nonionic surfactant Tween 20 to prepare a blend.

Table # 3

Experimental Example 1): Test for Weeding Prior to Germination and Crop Damage by Soil Treatment (Field Conditions)

After filling a rectangular plastic container (20 × 15 × 10cm) with sterilized field soil (sand loam, pH 5.5-6.0), sowing cotton with a surface area of 300㎡ and planting 8 weeds in one container And vomited at 0.5 cm. After 1 day of irrigation, a portion (12 ml per plastic container) containing the active ingredient corresponding to the treatment dose in the solution of 1 in the formulation was evenly sprayed onto the soil surface. For 30 days after the treatment, the herbicidal power against the plant cultivation and the observed weeds and the damage to the crops were evaluated according to the evaluation criteria.

Table # 4

Experimental Example 2): Herbicide and Drug Weakness Assay after Germination by Competitive Treatment (Foot Condition)

After seeding the assay plants in the same manner as in Example 1 and cultivating for 10 to 14 days, when the plants reached 3 to 4 foliar phase, a part containing the active ingredient corresponding to the amount of the treatment in Formulation Example 1 (12 ml per plastic container) Spray the plant uniformly on the plant management site. For 30 days after the treatment, weeding and weeding resistance to weeds and crops were evaluated according to the evaluation criteria.

Table # 5

Experimental Example 3): Control of herbicidal efficacy and cotton weakness during germination treatment

As a control agent, a methyl ester compound (A) and a phenoxyethyl ester compound (B) of 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid are known in the art (Europe) In accordance with the patent application No. 249,708), the effect on weeds and cotton was tested according to the method of Experimental Example 1. As a result, the novel phenylimino ester derivative represented by the general formula (I) according to the present invention was confirmed that not only the herbicidal effect is much superior, but also no harm to cotton.

Table # 6

Experimental Example 4): Control of herbicidal efficacy and cotton weakness in the treatment after germination

As in the case of Experiment 3, the control drugs (A) and (B) and the novel phenylimino ester compounds of the present invention were tested according to the method of Experiment 2, and as a result, the compounds of the present invention were stable to cotton It can be confirmed that the effect is excellent.

Table # 7

Claims (7)

Heteroarylimino ester derivatives and isomers thereof of the novel 6-chloro-2- (4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid represented by the following general formula (I). Wherein Q represents pyridine, furan, methylfuran, benzofuran, dimethylfuran, thiophene, chlorothiophene, methylthiophene, dimethylthiophene or methylpyrrole, and R is methyl, chlorine, methoxy, methylthio or A methoxycarbonyl group is shown. A process for producing a compound of formula (I), wherein the compound of formula (II) is reacted with a compound of formula (III). Wherein Q represents pyridine, furan, methylfuran, benzofuran, dimethylfuran, thiophene, chlorothiophene, methylthiophene, dimethylthiophene or methylpyrrole and R represents methyl, chlorine methoxy, methylthio or meth An oxycarbonyl group is shown. The method of claim 2 wherein the reaction is carried out in the presence of a metal salt. The method of claim 3 wherein the metal salt is CuBr ₂ or CuCl ₂ . The method of claim 2 or 3, wherein the reaction solvent is CH ₂ Cl ₂ , CHCl ₃ , CCl ₄ , CH ₂ ClCH ₂ Cl, CH ₃ CN or CH ₃ CH ₂ CN. The method of claim 2, wherein the reaction is carried out by refluxing xylene as a solvent in the absence of a metal salt. A herbicide composition comprising a compound of formula (I) as defined in claim 1 together with a generally acceptable carrier.