RU2162849C2 - Benzene derivative substituted by heterocycle, and herbicide - Google Patents

Abstract

FIELD: chemical industry. SUBSTANCE: described are new compounds of formula I:

or salts thereof wherein R¹ is C_1-6 alkyl group; R² is C_1-6 alkylsulfonyl group; R³ is C_1-6 alkyl group R⁴ is hydrogen and R is C_1-6 alkyl group and herbicidal composition comprising compound I or salt thereof as active agent. EFFECT: selectivity of herbicidal activity to crops and weeds, more particularly corn. 4 cl, 4 ex, 2 tbl

Description

 The invention relates to a new pyrazole derivative substituted with a benzoyl group at position 4 of the pyrazole ring and a herbicide.

описано в качестве активного компонента гербицида, имеющего скелет пиразола, замещенного бензоильной группой в положении 4 кольца пиразола.BACKGROUND OF THE INVENTION In WO 93/18031 Gazette, a compound of formula [II]:

described as an active component of a herbicide having a pyrazole skeleton substituted with a benzoyl group at position 4 of the pyrazole ring.

Описание изобретения
Цель данного изобретения - создать гербицид, который можно выгодно синтезировать в промышленных масштабах, который является устойчиво эффективным при более низких дозах и высоко безопасным, а также имеет более высокую избирательность в плане его гербицидной активности в отношении сорняков и культурных растений.On the other hand, WO 96/26206 Gazette describes a compound of the formula [III]:

Description of the invention
The purpose of this invention is to create a herbicide that can be advantageously synthesized on an industrial scale, which is stably effective at lower doses and highly safe, and also has a higher selectivity in terms of its herbicidal activity against weeds and crops.

This invention relates to a herbicide which contains, as an effective component, a 4-benzoyl-pyrazole derivative structurally characterized in that position 3 of the benzoyl moiety of the molecule represented by general formula [I] is substituted with a heterocycle and the substituent in position 2 is C _1-6 alkyl group.

где R¹ обозначает C_1-6 алкильную группу,
R² обозначает атом галогена, C_1-6 алкилтиогруппу, C_1-6 алкилсульфинилгруппу или C_1-6 алкилсульфонилгруппу,
R³ и R⁴ обозначают, каждый независимо, водород, C_1-6 алкильную группу или C_1-6 галогеналкильную группу и
R обозначает атом водорода или C_1-6 алкильную группу,
и гербицидному составу, содержащему такое соединение или такую соль.It should be said that this invention relates to a compound of formula [I] or a salt thereof:

where R ¹ denotes a C _1-6 alkyl group,
R ² represents a halogen atom, a C _1-6 alkylthio group, a C _1-6 alkylsulfinyl group or a C _1-6 alkylsulfonyl group,
R ³ and R ⁴ are each independently hydrogen, a C _1-6 alkyl group or a C _1-6 haloalkyl group and
R represents a hydrogen atom or a C _1-6 alkyl group,
and a herbicidal composition containing such a compound or such a salt.

 So, the following is a detailed description of the present invention.

и гербицидному составу, содержащему такое соединение в качестве активного компонента.This invention relates to a pyrazole derivative of the formula [I] or a salt thereof:

and a herbicidal composition containing such a compound as an active ingredient.

In the formula [I], R ¹ is a C _1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl and tert-butyl.

R ² is a halogen atom such as fluorine, chlorine and bromine, a C _1-6 alkylthio group such as methylthio, ethylthio, propylthio and isopropylthio, a C _1-6 alkylsulfinyl group such as methylsulfinyl, ethylsulfinyl, propylsulfinyl and isopropylsulfinyl, or C _{1- 6 an} alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl and isopropylsulfonyl.

R ³ and R ⁴ are each independently hydrogen, C _1-6 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl and tert-butyl, or C _1-6 haloalkyl, such as trifluoromethyl and trifluoroethyl.

R represents a hydrogen atom or C _1-6 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl.

Getting connections
Compounds according to this invention can be obtained according to the following reaction process.

где R¹, R², R³, R⁴ и R определены выше, и Q обозначает атом галогена, алкилкарбонилоксигруппу, алкоксикарбонилоксигруппу или бензоилоксигруппу.

where R ¹ , R ² , R ³ , R ⁴ and R are as defined above, and Q is a halogen atom, an alkylcarbonyloxy group, an alkoxycarbonyloxy group or a benzoyloxy group.

 In the process illustrated above, the compounds of formula [IVa] and [IVb] can respectively be obtained by reacting a compound of formula [VII] in an amount of 1 mol with a compound of formula [Va] in an amount of 1 mol, where Q is the same as as indicated above, wherein an excess of either a compound of the formula [VII] or a compound of the formula [Va], in the presence of a base in an amount of 1 mol or in an excess amount, can be used in the specified reaction.

As an example of a base that can be used in the reaction described above, alkali metal hydroxide such as KOH and NaOH, alkali metal carbonate such as sodium carbonate and potassium carbonate, alkaline earth metal hydroxide such as calcium hydroxide and hydroxide can be cited. magnesium, an alkaline earth metal carbonate such as calcium carbonate, a tri (C _1-6 alkyl) amine such as triethylamine and diisopropylethylamine, an organic base such as pyridine, and sodium phosphate and the like.

 In addition, water, methylene chloride, chloroform, toluene, ethyl acetate, dimethylformamide (DMF), tetrahydrofuran (THF), dimethoxyethane (DME), acetonitrile and the like can be mentioned as an example of a solvent that can be used in the reaction described above. .

The mixture prepared for the above reaction is stirred at a temperature in the range from 0 ^° C. to the boiling point of the solvent used throughout the period until the completion of the reaction. In addition, the reaction can be carried out in a two-phase system using an interphase catalyst, such as a quaternary ammonium salt.

In addition, compounds of formulas [IVa] and [IVb] can also be prepared by reacting a compound of formula [VII] and a compound of formula [Vb] in the presence of a dehydrocondensation agent such as dicyclohexylcarbodiimide (DCC). Examples of a solvent that can be used in reaction with DCC or the like include methylene chloride, chloroform, toluene, ethyl acetate, DMF, THF, dimethoxyethane, acetonitrile and tert-amyl alcohol. The reaction mixture is stirred at a temperature in the range of -10 ^° C. to the boiling point of the solvent used until the reaction is complete. The reaction mixture can be processed in the usual way.

The compounds of formulas [IVa] and [IVb] are used as a mixture in the following conversion reaction. The conversion reaction can be carried out in the presence of a cyano compound and a soft base. It should be said that the compound of formula [I] can be obtained by reacting a mixture of compounds of formulas [IVa] and [IVb] in an amount of 1 mol with a base in an amount of 1 to 4 mol, preferably 1-2 mol, and a cyano compound in an amount of 0 01 to 1.0 mol, preferably 0.05-0.2 mol. As the base that can be used here, any of the above bases may be used. In addition, potassium cyanide, sodium cyanide, acetone cyanohydrin, hydrocyanic acid and a polymer containing potassium cyanide are given as examples of the cyano compound. If a small amount of an interfacial catalyst, such as crown ether, is added, the reaction can be completed in a shorter period of time. The reaction temperature is less than 80 ^° C., preferably in the range from room temperature to 40 ^° C. Examples of the solvent described above are 1,2-dichloroethane, toluene, acetonitrile, methylene chloride, chloroform, ethyl acetate, DMF, methyl isobutyl ketone, THF and dimethoxyethane.

 In addition, this conversion reaction can also be carried out in a solvent in the presence of a base such as potassium carbonate, sodium carbonate, triethylamine and pyridine. The amount of base to be used in the reaction is in the range from 0.5 to 2.0 mol based on the compounds of the formulas [IVa] and [IVb], and THF, dioxane, tert- amyl alcohol and tert-butyl alcohol. The reaction temperature ranges from room temperature to the boiling point of the solvent used.

 In addition, a similar conversion reaction can also be carried out by adding a cyano compound and a base, as described above, to the reaction mixture without isolating the compounds of formulas [IVa] and [IVb].

 Moreover, the compound of formula [I] can also be obtained using a base together with a dehydrocondensation agent such as DCC, without isolating the compounds of formulas [IVa] and [IVb]. Potassium carbonate, sodium carbonate, triethylamine and pyridine are given as examples of the above bases. The amount of base used here is in the range from 0.5 to 2.0 mol, based on the compound of formula [VII]. In addition, THF, dioxane, tert-amyl alcohol, tert-butyl alcohol and the like are shown as examples of a solvent suitable for use in this reaction, and the reaction temperature is in the range of room temperature to the boiling point of the solvent used.

 Derivatives of 5-hydroxypyrazole of the formula [VII] can be obtained according to the following processes, which are described in the Japanese patent publication Laid-open N Sho 62-234069 Gazette and in the Japanese patent publication Laid-open N Hei 3-44375 Gazette.

(b)

Производное альдегида формулы (3) и производное карбоновой кислоты формулы (4), которые являются важными синтетическими промежуточными соединениями в получении соединения согласно данному изобретению, могут быть получены согласно следующей формуле реакции.

(b)

The aldehyde derivative of the formula (3) and the carboxylic acid derivative of the formula (4), which are important synthetic intermediates in the preparation of the compounds of this invention, can be obtained according to the following reaction formula.

где R¹ и R² обозначают то же, что указано выше, R⁶ обозначает водород или низшую алкильную группу и W обозначает атом галогена.

where R ¹ and R ² are the same as defined above, R ⁶ is hydrogen or a lower alkyl group, and W is a halogen atom.

The aldehyde compound of formula (3) can be obtained from a toluene derivative of formula (1) according to a known method, for example, by exposure to either a single halogen such as chlorine and bromine, or a halogenation agent such as N-bromosuccinimide (NBS) and N-chlorosuccinimide (NCS), in the presence of light (a photoinitiator) or a radical initiator of the reaction, such as benzoyl peroxide, to obtain a benzyl halide derivative of the formula (2), then converting it in accordance with the method described in J. Am. Chem. Soc. , Vol. 71, p. 1767 (1949), into an aldehyde compound of the formula (3). More specifically, an aldehyde compound of formula (3) can be prepared by reacting a benzyl halide derivative of formula (2) with an alkali metal salt of a nitroalkane such as 2-nitropropane in an alcohol solvent such as methanol and ethanol at a temperature of from 0 ^° C. to boiling point solvent used.

 Further, a carboxylic acid derivative of formula (4) can be obtained from a toluene derivative of formula (1) by an oxidation reaction with potassium permanganate or the like, or, alternatively, it can be obtained from an aldehyde compound of formula (3) according to a known method using the reaction oxidation with any of the Jones reagents, chromic acid, potassium permanganate, or the like.

 In addition, using both the aldehyde compound of the formula (3) and the carboxylic acid derivative of the formula (4), intermediates can be prepared as shown below.

где R¹, R² и R⁶ обозначают то же, что указано выше, R⁷ обозначает низшую алкильную группу и R⁴ обозначает водород или низшую алкильную группу.

where R ¹ , R ² and R ⁶ are the same as defined above, R ⁷ is a lower alkyl group and R ⁴ is hydrogen or a lower alkyl group.

 The corresponding acyl compound of formula (6) can be obtained by first producing an alcohol derivative of formula (5), which can be obtained by reacting an aldehyde compound of formula (3) with a Grignard reagent, and then oxidizing the alcohol derivative of formula (5) with any of the activated manganese dioxide, chromic acid and the like.

A vinyl ketone derivative of formula (10) can be prepared by reacting an aldehyde compound of formula (3) with a methyl ketone derivative of formula (7) in the presence of a catalyst at a temperature of from 0 to 100 ^° C. for 1 to 50 hours in a solvent such as water, toluene and chloroform or a mixed solvent of water and toluene, chloroform and the like, until the formation of the aldol compound of formula (8) and then dehydration of the aldol compound in the presence of a catalyst in a suitable solvent.

 As examples of the catalyst used in the reaction for producing said aldol compound of formula (8), metal hydroxide such as sodium hydroxide and barium hydroxide and an organic base such as piperidine and pyridine are given.

 In addition, acids such as concentrated sulfuric acid and p-toluenesulfonic acid are given as examples of a catalyst that can be used in the dehydration reaction described above. In addition, hydrocarbon such as benzene and toluene and a halogenated hydrocarbon such as dichloromethane and chloroform are given as examples of the solvent used in said dehydration reaction.

 A vinylketone derivative of formula (10) can also be prepared by reacting an aldehyde compound of formula (3) with a phospholane compound of formula (9) in a suitable solvent at a temperature in the range from room temperature to the boiling point of the solvent used over a period of 10 minutes to 30 hours.

 The β-diketone derivative of formula (12) can be prepared according to the following process.

где R¹, R², R³ и R⁶ обозначают то же, что указано выше, и R" и R⁹ обозначают, каждый независимо, низшую алкильную группу.

where R ¹ , R ² , R ³ and R ⁶ are the same as defined above, and R "and R ⁹ are each independently a lower alkyl group.

 During the reaction, as shown above, the carboxylic acid derivative of formula (4) is reacted with a chlorination agent such as phosgene, thionyl chloride and oxalyl chloride in an inert solvent such as a hydrocarbon like benzene or toluene and a halogenated hydrocarbon like methylene chloride or chloroform to obtain a carbonyl chloride derivative of the formula (11), which is an intermediate.

 Then, the β-diketone derivative of the formula (12) can be obtained by reacting the carbonyl chloride derivative of the formula (11) with a magnesium salt of the β-keto ester derivative (13), this salt can be obtained by reacting the β-keto ester derivative of the formula (13) with an alcoholate magnesium in accordance with a known method.

 The following is an explanation of the method for producing the isoxazole derivative, which is an intermediate.

В указанном выше процессе реакции R¹, R², R³ и R⁶ имеют указанные выше значения.Production Method 1

In the above reaction process, R ¹ , R ² , R ³ and R ⁶ are as defined above.

An isoxazole derivative of formula (15a) can be prepared by first reacting a vinyl ketone derivative of formula (10) with hydroxylamine in an appropriate solvent at a temperature in the range of from 0 ^° C. to the boiling point of the solvent used for a period of 0.5 to 5 hours before the formation of the oxime derivative formula (14) and the subsequent exposure of the specified derivative of the oxime cyclization reaction and oxidation reaction. In this oxime formation reaction, either sulfate or hydroxylamine hydrochloride can be used even without neutralization, however, such hydroxylamine salts can be used after neutralizing them with a suitable base.

 Examples of the base used in the reaction include carbonate, such as sodium hydrogen carbonate and potassium carbonate, alkali metal hydroxide, such as sodium hydroxide and potassium hydroxide, carboxylate, such as sodium acetate, metal alcoholate, such as sodium methylate and ethylate sodium, and an organic base such as triethylamine and pyridine.

 In addition, alcohol, such as methanol, ethanol and isopropanol, a hydrocarbon such as benzene and toluene, a halogenated hydrocarbon such as dichloromethane and chloroform, an ether such as THF and dioxane, nitrile are given as examples of the solvent used in the reaction. such as acetonitrile, DMF, pyridine, acetic acid, water and a mixed solvent of two or more of these solvents.

 A mixture of potassium iodide, N-bromo-succinimide or a palladium catalyst can be used in the cyclization and oxidation reactions described above, and the target compounds can be prepared according to the method described in J. Am. Chem. Soc., P. 94 (1972), J. Heterocyci. Chem., Vol. 14, p. 1289 (1977) and Tetrahedron Lett. p. 5075 (1977).

В описанном выше процессе реакции R¹, R², R³, R⁴ и R⁶ обозначают то же, что указано выше.The method of obtaining 2

In the above reaction process, R ¹ , R ² , R ³ , R ⁴ and R ⁶ are the same as described above.

An isoxazole derivative of formula (15) can also be prepared by reacting a β-diketone derivative of formula (12) with either hydroxylamine or a hydroxylamine salt. This reaction can be carried out in a suitable solvent at a temperature in the range from 0 ^° C. to the boiling point of the solvent used. An acid such as sulfuric acid and p-toluenesulfonic acid may also be used as a catalyst in this reaction.

 Examples of the solvent used in the reaction are alcohol, such as methanol, ethanol and isopropanol, a hydrocarbon, such as benzene and toluene, a halogenated hydrocarbon, such as dichloromethane and chloroform, an ether, such as THF and dioxane, nitrile, such as acetonitrile, DMF, pyridine, acetic acid, water, and a mixed solvent of two or more of these solvents.

В описанном выше процессе реакции R¹, R², R³, R⁴ и R⁶ обозначают то же, что указано выше, и r₁, r₂ и R' обозначают, каждый независимо, низшую алкильную группу.The method of obtaining 3

In the above reaction process, R ¹ , R ² , R ³ , R ⁴ and R ⁶ are the same as defined above, and r ₁ , r ₂ and R ′ are each independently a lower alkyl group.

 Alternatively, an isoxazole derivative of formula (15) can be prepared by reacting a dialkylaminomethylidene derivative of formula (16) (which is prepared by reacting a 3-acyl compound of formula (6) described above with an N, N-dialkylalkylamide dialkyl acetal such as N, N-dimethylacetamide dimethyl acetal ) either with hydroxylamine or with a hydroxylamine salt.

В описанном выше реакционном процессе R¹, R³, R⁴ и R⁶ обозначают то же, что указано выше, и R' обозначает C_1-6 алкильную группу.The method of obtaining 4

In the above reaction process, R ¹ , R ³ , R ⁴ and R ⁶ are the same as defined above, and R ′ is a C _1-6 alkyl group.

 In addition, a benzoic acid derivative of formula (15b) can be prepared by reacting a mercapto compound of formula R'SH with a 4-Cl compound of formula (1-2) in the presence of a base to form a 4-SR 'compound of formula (1-3) and subsequent oxidation of said 4-SR 'connection.

 As examples of the base used in this reaction, alkali metal hydroxide such as sodium hydroxide and potassium hydroxide, metal alkoxide such as sodium methoxide and sodium ethoxide, carbonate such as sodium carbonate and potassium carbonate, hydride such as sodium hydride, and an organic base such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] unde-7-cen (DBU) and pyridine. In addition, alcohol, such as methanol and ethanol, an ether, such as THF and 1,2-dimethoxyethane (DME), an amide, such as DMF and N, N-dimethylacetamide can be cited as examples of the solvent used in the reaction. (DMA), dimethyl sulfoxide (DMSO), acetonitrile, benzene, toluene and xylene. The subsequent oxidation reaction is carried out using any oxidizing agent, such as peroxide, such as hydrogen peroxide, peracetic acid, perbenzoic acid and m-chloroperbenzoic acid, or hypochlorous acid, such as sodium hypochlorite and potassium hypochlorite, in an inert solvent, including water, an organic an acid such as acetic acid; and a halogenated hydrocarbon such as dichloromethane, chloroform and carbon tetrachloride. The reaction can proceed smoothly in the temperature range from room temperature to the boiling point of the solvent used.

 Alternatively, a compound of formula (1-3) can be prepared by reacting a mercapto salt, which is previously obtained by reaction with a mercapto compound of formula R'SH and a base, with a compound of formula (1-2).

The method of obtaining 5
In addition, the compound of formula (15) can be obtained according to the method described in WO 96/26206 Gazette. The following is a method for producing said compound of formula (15).

В описанном выше процессе реакции R¹, R², R³ и R⁶ обозначают то же, что указано выше, Y обозначает Br, I, OSO₂CF₃ и M обозначает Sn(C_1-6 алкил)₃, B(OH)₂ или ZnCl.

In the above reaction process, R ¹ , R ² , R ³ and R ⁶ are the same as above, Y is Br, I, OSO ₂ CF _3, and M is Sn (C _1-6 alkyl) ₃ , B (OH ) ₂ or ZnCl.

 Various types of tautomers, as illustrated hereinafter, may be present in the compounds of formula [I] according to this invention. Therefore, it should be noted that all of these tautomers fall within the scope of the invention.

Соединения данного изобретения и различные промежуточные соединения могут быть получены путем проведения соответствующей последующей обработки после завершения реакции обычными методиками.

The compounds of this invention and various intermediates can be obtained by appropriate post-treatment after completion of the reaction by conventional methods.

 The structures of the compounds of this invention and various intermediates for their preparation are determined by IR, NMR, MS and other available means.

Preferred Embodiment
Now the invention is described in more detail with reference to examples and comparative examples described below, however, the scope of the invention should not be limited to one of these described examples.

4-метансульфонил-2-метил-3-(3-метил-1,2-изоксазол-5-ил)бензойную кислоту в количестве 1,35 г (4,61 ммоль) растворяют в 15 мл бензола и добавляют 0,71 г (5,97 ммоль) тионил-хлорида и одну каплю пиридина с последующим перемешиванием в течение 2 часов при кипячении с обратным холодильником. После этого раствору позволяют остыть, растворитель отгоняют при пониженном давлении, чтобы получить 1,43 г 4-метансульфонил-2-метил-3-(3-метил-1,2-изоксазол-5-ил)бензоилхлорида.Example 1
Preparation of 1-ethyl-5-hydroxy-4- [4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl)] benzoylpyrazole

1.35 g (4.61 mmol) of 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoic acid are dissolved in 15 ml of benzene and 0.71 g is added (5.97 mmol) of thionyl chloride and one drop of pyridine, followed by stirring for 2 hours at the boil under reflux. After this, the solution was allowed to cool, the solvent was distilled off under reduced pressure to obtain 1.43 g of 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoyl chloride.

0.38 g (2.6 mmol) of 1-ethyl-5-hydroxypyrazole hydrochloride and 0.51 g (5.1 mmol) of triethylamine are dissolved in 10 ml of methylene chloride and 2 ml of a methylene chloride solution containing 0 is added dropwise at room temperature. 71 g (2.3 mmol) of 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoyl chloride, followed by stirring at room temperature for 1 hour. The resulting reaction mixture was washed with 1 N. hydrochloric acid and then a saturated solution of sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting precipitate was dissolved in 10 ml of acetonitrile and 0.47 g (4.7 mmol) of triethylamine and 0.06 g (0.7 mmol) of acetone cyanhydrin were added, followed by stirring at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate. After that, the solution is washed with 1 N. hydrochloric acid and then a saturated solution of sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The remaining crystals are washed with methanol to obtain 0.50 g of the target compound. Mp = 186-189 ^o C.

 Typical examples of the compounds obtained according to this invention, as described above, are given in table 1.

10,8 г (0,045 моль) метил-2,3-диметил-4-метансульфонилбензоата растворяют в 80 мл тетрахлорида углерода и затем добавляют 8,3 г (0,047 моль) N-бромсукцинимида и 0,1 г пероксида бензоила с последующим перемешиванием в течение 3 часов при нагревании с обратным холодильником. После этого раствору позволяют остыть, нерастворенное вещество удаляют фильтрованием, а полученный фильтрат промывают водным раствором кислого бисульфита натрия и затем сушат над безводным сульфатом магния. Затем растворитель отгоняют при пониженном давлении, остаток очищают колоночной хроматографией на силикагеле, чтобы получить 6,2 г метил-3-бромметил-4-метансульфонил-2-метилбензоата в кристаллическом состоянии. Выход = 43,4%.Reference Example 1
Preparation of methyl 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoate

10.8 g (0.045 mol) of methyl 2,3-dimethyl-4-methanesulfonylbenzoate are dissolved in 80 ml of carbon tetrachloride and then 8.3 g (0.047 mol) of N-bromosuccinimide and 0.1 g of benzoyl peroxide are added, followed by stirring in for 3 hours when heated under reflux. After this, the solution was allowed to cool, the insoluble matter was removed by filtration, and the obtained filtrate was washed with an aqueous solution of sodium hydrogen sulphite and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 6.2 g of crystalline methyl 3-bromomethyl-4-methanesulfonyl-2-methylbenzoate. Yield = 43.4%.

 2.6 g (0.014 mol) of a methanol solution containing 28% sodium methylate are added to 20 ml of methanol and 1.3 g (0.015 mol) of 2-nitropropane are added dropwise at room temperature. Then, 4.4 g (0.014 mol) of methyl 3-bromomethyl-4-methanesulfonyl-2-methylbenzoate are added, followed by stirring for 1 hour under reflux. After this, the solution is allowed to cool, add 50 ml of 1 N. hydrochloric acid to the reaction solution, extraction is carried out with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. Then, the solution was evaporated (concentrated) under reduced pressure to obtain 3.1 g of methyl-3-formyl-4-methanesulfonyl-2-methylbenzoate in a crystalline state. Yield = 88%.

 30 ml of benzene and then 3.85 g (0.012 mol) of 2-oxopropylidene triphenylphospholane are added to 3.1 g (0.012 mol) of methyl 3-formyl-4-methanesulfonyl-2-methylbenzoate, followed by stirring for 1 hour under reflux a refrigerator. Then the solution is allowed to cool. The insoluble matter was removed by filtration, and the solution was concentrated under reduced pressure to obtain methyl 4-methanesulfonyl-3- (3-oxo-1-butenyl) -2-methylbenzoate. The methyl 4-methanesulfonyl-3- (3-oxo-1-butenyl) -2-methylbenzoate thus obtained was dissolved in a solvent of 10 ml of ethanol and 10 ml of pyridine, and 1.1 g (0.016 mol) of hydroxylamine hydrochloride was added thereto, followed by stirring for 1 hour at the boil under reflux. The resulting reaction mixture was poured into ice water and extraction was performed with ethyl acetate. After that, the resulting ethyl acetate layer was washed with 1 N. hydrochloric acid and then a saturated solution of sodium chloride and then dried over anhydrous magnesium sulfate. After that, the solvent is distilled off under reduced pressure. The methyl 4-methanesulfonyl-3- (3-hydroxyimino-1-butenyl) -2-methylbenzoate thus obtained was dissolved in 15 ml of THF, and 15 ml of water containing 1.4 g (0.017 mol) of sodium bicarbonate was added to the solution. Following this, an aqueous solution is added, obtained by dissolving 2.5 g (0.015 mol) of potassium iodide and 1.1 g (0.05 mol) of iodine in 12 ml of water, and the solution is heated under reflux for 3 hours under conditions without access Sveta. The reaction mixture was poured into ice water and sodium hydrogen sulfite was added, followed by extraction with ethyl acetate. The resulting organic layer was washed with a saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. After that, the solvent is distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain 0.84 g of methyl-4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoate. Yield = 23%.

¹ H-NMR (CDCl ₃ , δ ppm): 2.36 (3H, s), 2.45 (3H, s), 2.92 (3H, s), 3.98 (3H, s) 6.41 (1H, s), 8.07 (1H, d), 8.16 (1H, d).

10 г (0,044 моль) метил-3-метокси-2-метил-4-метилтиобензоата растворяют в 90 мл метиленхлорида и раствор добавляют по каплям к 90 мл метиленхлорида, содержащего 8,4 мл (0,088 моль) трибромида бора, при 5-10^oC. После перемешивания при комнатной температуре в течение 4 часов добавляют по каплям 50 мл метанола при охлаждении льдом и затем промывают раствор водой, а потом насыщенным раствором хлорида натрия. После сушки над безводным сульфатом магния растворитель отгоняют при пониженном давлении, чтобы получить 9,2 г метил-3-гидрокси-2-метил-4-метилтиобензоата. Выход = 98%.Reference Example 2
Preparation of methyl 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoate

10 g (0.044 mol) of methyl 3-methoxy-2-methyl-4-methylthiobenzoate are dissolved in 90 ml of methylene chloride and the solution is added dropwise to 90 ml of methylene chloride containing 8.4 ml (0.088 mol) of boron tribromide, at 5-10 ^o C. After stirring at room temperature for 4 hours, 50 ml of methanol are added dropwise under ice-cooling, and then the solution is washed with water and then with a saturated solution of sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 9.2 g of methyl 3-hydroxy-2-methyl-4-methylthiobenzoate. Yield = 98%.

9.2 g (0.043 mol) of methyl 3-hydroxy-2-methyl-4-methylthiobenzoate are dissolved in 50 ml of acetic acid and then 14.8 g (0.130 mol) of 30% hydrogen peroxide are added, followed by stirring at 80 ^o C for 3 hours. Then the reaction mixture was poured into ice water and the precipitated crystals were collected by filtration, washed with water and then dried to obtain 8.8 g of methyl 3-hydroxy-4-methanesulfonyl-2-methylbenzoate. Yield = 83%.

8.8 g (0.036 mol) of methyl 3-hydroxy-4-methanesulfonyl-2-methylbenzoate are dissolved in 100 ml of methylene chloride and 8.3 g (0.11 mol) of pyridine are added. Then the solution is cooled to 0 ^° C., 12.2 g (0.043 mol) of trifluoromethanesulfonic anhydride are added. After stirring at room temperature for 1 hour, the reaction mixture was washed with 1 N. hydrochloric acid and then a saturated solution of sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 13.5 g of methyl 4-methanesulfonyl-2-methyl-3- (trifluoromethanesulfonyl) hydroxybenzoate. Yield = 99%.

1.65 g (4.4 mmol) of methyl 4-methanesulfonyl-2-methyl-3- (trifluoromethanesulfonyl) hydroxybenzoate and 1.97 g (5.3 mmol) of 3-methyl-5- (tributylstannyl) isoxazole are dissolved in 20 ml of dioxane and add 0.58 g (14 mmol) of lithium chloride, 0.1 g of tetrakis (triphenylphosphine) -palladium- (0) and 0.01 g of 2,6-di-tert-butyl-4-methylphenol, followed by stirring at 140 ^o C for 3 hours in an autoclave. The solution was then allowed to cool, the insoluble matter was removed by filtration, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.74 g of methyl-4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoate. Yield = 55%.

3,11 г (10,1 ммоль) метил-4-метансульфонил-2-метил-3-(3-метил-1,2-изоксазол-5-ил)бензоата растворяют в 30 мл метилового спирта и затем добавляют 30 мл 1 н. водного раствора едкого натра с последующим перемешиванием при комнатной температуре в течение ночи. Полученную реакционную смесь выливают в ледяную воду и затем подкисляют концентрированной хлористоводородной кислотой. После этого осажденные кристаллы собирают фильтрованием, промывают водой и затем сушат, чтобы получить 2,85 г 4-метансульфонил-2-метил-3-(3-метил-1,2-изоксазол-5-ил)бензойной кислоты. Выход = 96% и т.пл. = 242^oC.Reference Example 3
Preparation of 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoic acid

3.11 g (10.1 mmol) of methyl 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoate are dissolved in 30 ml of methyl alcohol and then 30 ml of 1 n aqueous sodium hydroxide solution, followed by stirring at room temperature overnight. The resulting reaction mixture was poured into ice water and then acidified with concentrated hydrochloric acid. Thereafter, the precipitated crystals were collected by filtration, washed with water and then dried to obtain 2.85 g of 4-methanesulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoic acid. Yield = 96% and mp. = 242 ^o C.

Obtaining compounds used for comparison
Compound A is for comparison purposes described in WO 93/17083 Gazette and compounds B and C are compounds described in WO 96/26206 Gazette. And also compound D is given as an example in Gazette WO 96/26206. Compound D was prepared according to the same method as described in Example 1 using 4-methane-sulfonyl-2-methyl-3- (3-methyl-1,2-isoxazol-5-yl) benzoic acid, which was obtained in the Reference Example 3, and 1,3-dimethyl-5-hydroxypyrazole as starting material. Mp = 137-139 ^o C.

Полезный эффект изобретения
Соединения данного изобретения могут обеспечивать высокую гербицидную активность даже в условиях двух способов нанесения, включая обработку почвы и нанесение на листву, в условиях полеводства, и они эффективны против различных видов вредных сорняков, таких как лисохвост, дурнишник, лебеда белая и овсюг. Соединения данного изобретения включают соединения, которые избирательно нетоксичны по отношению к культурным растениям, таким как кукуруза, пшеница, ячмень, соя и хлопок.

The beneficial effect of the invention
The compounds of this invention can provide high herbicidal activity even under two application methods, including soil treatment and foliage application, under field cultivation conditions, and they are effective against various types of harmful weeds such as foxtail, spring grass, white quinoa and wild oats. The compounds of this invention include compounds that are selectively non-toxic to crop plants such as corn, wheat, barley, soy and cotton.

 Moreover, the compounds of this invention include compounds that may exhibit the ability to regulate plant growth, such as growth inhibition, in relation to beneficial plants such as crops, ornamental flowering plants, fruit trees, etc.

 In addition, the compounds of this invention have a particularly good herbicidal effect on weeds such as chicken millet, Cyperus difformis, Sagittaria trifolia and Scirpus juncoides, and have selectivity for rice plants.

 Moreover, the compounds of this invention can be used for weed control in fruit nurseries, on lawns, railway tracks, empty land and the like.

Herbicide
The herbicidal preparation according to this invention contains one or more compounds of the present invention as active components. In actual use, the compound of the present invention can be used in its pure form without the addition of any other components, and for the purpose of using the compounds of the invention as a plant protection chemical, the compounds of the invention can be used in the form of a preparation commonly used in plant protection chemicals. For example, in the form of wettable powders, granules, dusts, emulsifiable concentrates, water-soluble powders, suspensions or flowable preparations. As an additive or carrier that can be used as part of a solid preparation, vegetable powders such as soy flour and wheat flour, fine mineral powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, pyrophyllite and clay can be used and organic and inorganic compounds such as sodium benzoate, urea and Glauber's salt. When it is intended to use a liquid preparation, a solvent may be used, for example, petroleum fractions such as kerosene, xylene and solvent naphtha, cyclohexane, cyclohexanone, dimethylformamide, dimethyl sulfoxide, alcohols, acetone, trichlorethylene, methyl isobutyl ketone, mineral oils , vegetable oils and water. In order to keep the preparation uniform and stable, a surfactant may be added if necessary.

 The concentration of the active component in the herbicidal preparation of the present invention depends on the form of the above agent, but, for example, in the case of a wettable powder, it is in the range from 5 to 90%, preferably from 10 to 85%; in the case of an emulsion, it is in the range from 3 to 70%, preferably from 5 to 60%; and in the case of granules, it is in the range from 0.01 to 50%, preferably from 0.05 to 40%.

 The wettable powder or emulsion thus obtained is respectively diluted to a predetermined concentration with water to obtain a suspension or emulsion, and the granules can simply be scattered on the soil or mixed with it before or after the germination of the weeds. In fact, when the herbicide of the present invention is used, a suitable amount of the active ingredient for application is 0.1 g or more per hectare.

 In addition, the herbicide of the present invention can be used in admixture with any of the known fungicides, insecticides, acaricides, other herbicides, plant growth regulators and fertilizers. In particular, when the herbicide of the present invention is mixed with other herbicides, the amount of the herbicide of the present invention can be reduced. In addition, the use of the herbicide of the present invention leads to lower labor costs, and higher effects of the present invention can also be expected due to the synergistic effect of the mixed agents. In this case, it is also possible to mix the herbicide of the present invention with many known herbicides.

 Examples of agents that are suitable for mixing with the herbicide of the present invention include anilide-containing herbicides such as diflufenican and propanyl, chloroacetanilide-containing herbicides such as alachlor and pretilachlor, herbicides containing aryloxyalkanoic acid such as 2,4-D and 2,4-DB , herbicides containing aryloxyphenoxyalkanoic acid, such as diclofop-methyl and phenoxapropetyl, herbicides containing arylcarboxylic acid, such as dicamba and pyritiobac sodium, herbicides containing imidazolinone, such as imazacvin and im zetapyr, urea-containing herbicides such as diuron and isoproturon, carbamate-containing herbicides such as chlorprofam and phenmedifam, thiocarbamate-containing herbicides such as thiobencarb and EPTS, herbicides containing dinitroaniline, such as trifluralin g and pend diphenyl ether, such as acifluorfen sodium and fomesafen, herbicides containing sulfonyl urea, such as bensulfuron-methyl and nicosulfuron, herbicides containing triazinone, such as metribuzin and metamitron, herbicides containing triazine-containing, such as atrazine and cyanazine, triazopyrimidine-containing herbicides, such as flumetsulam, nitrile-containing herbicides, such as bromoxynil and dichlobenil, pyridazinone-containing herbicides, such as chloridazone and norflurazone, phosphoric acid and phosphoric acid , herbicides containing a quaternary ammonium salt, such as paraquat and diphenzoquat, herbicides containing a cyclic amide such as flumiclorac-pentyl and flutiacet-methyl, other herbicides such as isoxaben, et fumezat, oxadiazon, quinclorac, clomazone, sulcotrione, cinmethylin, dithiopyr, pyrazolate, pyridate, flupoxam, bentazone and benfurezat, and herbicides containing cyclohexanedione such as sethoxydim and tralkoxydim. In addition, vegetable oil or oily condensate may be added to the mixture of these active ingredients.

Examples
Herbicide
The following are some examples of the formulations of the herbicidal preparation according to this invention, however, the compounds of the active component, additives and their ratio are not limited by what is described in these examples, and they can vary or expand over a wide range. In the examples of the formulations, "part (s)" means "part (s) by weight".

Example 2. Wettable Powder Formulation
The compound of this invention is 20 parts
White soot - 20 parts
Diatomaceous earth - 52 parts
Sodium Alkyl Sulfate - 8 parts
These materials are uniformly mixed and then finely ground to obtain a wettable powder containing 20% effective component.

Example 3. The composition of the emulsifiable concentrate
The compound of this invention is 20 parts
Xylene - 55 parts
Dimethylformamide - 15 parts
Polyoxyethylene phenyl ether - 10 parts
These materials are uniformly mixed and dissolved to obtain an emulsion containing 20% effective component.

Example 4. Granular composition
The compound of this invention is 5 parts
Talc - 40 parts
Clay - 38 parts
Bentonite - 10 parts
Sodium Alkyl Sulfate - 7 Parts
These materials are uniformly mixed, finely ground and then granulated to obtain granules having a diameter of from 0.5 to 1.0 mm and containing 5% of the effective component.

Test examples
The following are test examples with respect to the herbicidal effect of the herbicides of the present invention.

 The herbicidal effect is evaluated in accordance with the following evaluation criterion and expressed as indicators reflecting the strength of the herbicidal preparation.

Evaluation Criteria:
Destroyed weeds,% - Herbicide rate
0 - 0
20-29 - 2
40-49 - 4
60-69 - 6
80-89 - 8
100 - 10
In addition, values 1, 3, 5, 7 and 9 denote values between 0 and 2, 2 and 4, 4 and 6, 6 and 8 and 8 and 10, respectively.

Пример испытания 1. Нанесение на листву наземной части сорняков на суходольных полях культурных посевов
Горшки размером 200 см² заполняют почвой и семена канатника, лебеды, дурнишника, лисохвоста и кукурузы высаживают в горшки, соответственно. После этого семена покрывают почвой, оставляют для выращивания в теплице. Когда растения вырастут до высоты 5-25 см, на стебли и листья сорняков распыляют небольшим распылителем разбавленные водные растворы эмульсии, указанной в примере 3, содержащей образцы соединения, так чтобы активный компонент в количестве 250 г/га был внесен в каждый из горшков. Через 3 недели оценивают гербицидные эффекты соответствующих соединений в отношении сорняков (результаты приведены в таблице 2). Показано, что соединения согласно данному изобретению обеспечивают превосходную гербицидную активность против различных типов сорняков и, в частности, имеют высокую селективность по отношению к растениям кукурузы, не оказывая на них вредного воздействия.

Test Example 1. Application of foliage of the ground part of weeds in dry fields of cultivated crops
Pots 200 cm ² in size are filled with soil and the seeds of the cableworm, quinoa, fruit cock, foxtail and corn are planted in the pots, respectively. After that, the seeds are covered with soil and left to grow in a greenhouse. When the plants grow to a height of 5-25 cm, dilute aqueous solutions of the emulsion specified in Example 3 containing samples of the compound are sprayed onto the stems and leaves of the weeds with a small sprayer so that the active ingredient in an amount of 250 g / ha is introduced into each of the pots. After 3 weeks, the herbicidal effects of the respective compounds against weeds were evaluated (the results are shown in table 2). It was shown that the compounds according to this invention provide excellent herbicidal activity against various types of weeds and, in particular, have high selectivity with respect to corn plants, without exerting harmful effects on them.

Possible industrial applications
As described above, the compound of the formula [1] has excellent selectivity of herbicidal activity towards cultivated plants and weeds and, in particular, it is selectively safe for corn plants. Therefore, a herbicidal preparation containing a compound of this invention may be useful as a selective herbicide for controlling weeds in corn fields.

Claims (3)

1. Derivatives of 4-benzoylpyrazole of the general formula I

or their salts,
where R ¹ represents a C _1-6 alkyl group;
R ² represents a C _1-6 alkylsulfonyl group;
R ³ represents a C _1-6 alkyl group;
R ⁴ is hydrogen;
R is a C _1-6 alkyl group. 2. The compound according to claim 1, where R ¹ and R ³ are methyl, R ² is methylsulfonyl, R ⁴ is hydrogen, and R is methyl or ethyl. 3. Herbicidal composition, characterized in that it contains as an active agent a compound of formula I

or its salt, where the values of R, R ¹ , R ² , R ³ and R ^{4 are} defined above.

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