JPH0236164A - Production of 2-nitro-5-(substituted aryloxy) benzohydroximic acid derivative - Google Patents

Abstract

PURPOSE:To obtain the subject compound for herbicides by nitrating a readily available novel compound, such as O-methoxycarbonylmethyl-3-(2-chloro-4- trifluoromethylphenoxy)benzohydroximate. CONSTITUTION:A novel compound expressed by formula I [Z is CX (X is H or halogen) or N; R<1> and R<3> are lower alkyl; R<2> is H or lower alkyl] is nitrated to afford a 2-nitro-5-(substituted aryloxy)benzohydroximic acid derivative expressed by formula II [e.g., methyl O-methoxycarbonylmethyl 5-(2-chloro-4- trifluoromethylphenoxy)-2-nitrobenzohydroximate]. The compound expressed by formula I is obtained by, e.g., reacting a compound expressed by formula III with a sulfurating agent to provide a compound expressed by formula IV, reacting the resultant compound expressed by formula IV with hydroxylamine and then reacting the obtained compound expressed by formula V with a compound expressed by formula VI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-nitro-5-(substituted aryloxy)benzohydroxymic acid derivatives, more specifically, in the following formula (I[), 2 is 2-nitro-5-, which is CX or a nitrogen atom, where X is hydrogen or a halogen atom, R1 and R3 are each a lower alkyl group, and R2 is a hydrogen atom or a lower alkyl group. The present invention relates to a method for producing (substituted aryloxy)benzohydroxymic acid derivatives.

PRIOR ART Conventionally, as a method for producing the compound of formula (U), there has been known a method of synthesizing the compound according to the steps shown in Reaction Formula A below [see JP-A-62-201860].

However, the raw material aminooxyalkanoic acid ester used in the amidation process is very expensive.

Furthermore, the method of reacting a halogen compound in the presence of a base in the alkylation step has the disadvantage of poor selectivity in 0-alkylation and very low yield.

In addition, in the alkylation process, when R1 in the above formula is a methyl group, diazomethane can be used, but diazomethane has the drawbacks of being expensive, highly toxic and explosive, and cannot be used industrially. have.

Problems to be Solved The object of the present invention is to provide compounds of the above formula (
The object of the present invention is to find a method for producing the compound (n) in a short reaction process using easily available and inexpensive raw materials.

SUMMARY OF THE INVENTION The present inventors have developed a commercially available 7-enyl ether represented by the formula (II) that exhibits high herbicidal activity with a small application amount, has a wide herbicidal spectrum, and has good selectivity for major crops. Intensive research efforts were made to establish the perfect manufacturing method.

As a result, the compound represented by the formula (I), which has not been described in the conventional literature, was used as a starting material, and by nitrating it, the compound represented by the formula (I), which is very useful as a herbicide, was obtained in step 1.
We have discovered an industrially advantageous method for producing the phenyl ethers represented by I).

Thus, according to the present invention, in the following formula (I), 2 is C
X or a nitrogen atom, where X is a hydrogen or halogen atom, R1 and R3 are each a lower alkyl group, and R2 is a hydrogen atom or a lower alkyl group. Provided is a method for producing a compound represented by the following formula (n), wherein ZSR', R'' and R3 are as defined above.

It should be understood that the compounds represented by formulas (I) and (n) above may exist as stereoisomers (Syn and Anti forms), both of which are within the scope of the present invention.

The method of the present invention is based on the above formula (I) used as a starting material.
) The compound represented by formula (I This is a very useful method for industrially producing phenyl ethers at low cost.

Furthermore, according to the method of the present invention, Anti
Even if a mixture of Syn type and Anti type compounds with a high type content is used, a Syn type compound is preferentially produced in the reaction product, and by post-processing this reaction product such as crystallization,
Syn-type compounds can be obtained in pure form.

DETAILED DESCRIPTION OF THE INVENTION As used herein, "halogen atoms" include, for example, fluorine, chlorine, bromine or iodine atoms. Among these, fluorine or chlorine atoms are preferred.

Furthermore, in this specification, the term "lower" means that the number of carbon atoms in the atomic group or compound to which this term is attached is 6 or less, preferably 4 or less.

Thus, a "lower alkyl group" may be of either linear or branched type, such as methyl, ethyl, n-propyl, i-propyl, n-butyl,
Examples include S-butyl, i-butyl, t-butyl, n-amyl, and the like.

In the above method, the nitrating agent used for nitrating the compound of formula (I) includes conventional nitrating agents such as nitric acid/sulfuric acid, sodium nitrate/sulfuric acid, potassium nitrate/sulfuric acid, and the like.

The amount of these nitrating agents used is not strictly limited, but generally 1 to 10
It is appropriate to use it in moles, preferably in the range of 1 to 3 moles. In addition, the reaction temperature can be changed depending on the type of nitrating agent, etc., but it is generally between -20°C and 100°C.
, preferably in the range of -10°C to 80°C, and the reaction is normally carried out at such temperatures between 0.5 and 5°C.
It can be completed in about an hour.

Furthermore, the above nitration reaction may be carried out without a solvent,
Alternatively, it may be carried out in a solvent such as dichloromethane, dichloroethane, etc.

After completion of the reaction, the reaction mixture, for example, is poured into water, extracted with an organic solvent, and crystallized, whereby the target compound of formula (I[) can be easily isolated in a good yield.

Formula (I) used as starting material in the process of the invention
) is a new compound, and can be synthesized, for example, by the method shown in Reaction Formula B below.

Reaction formula B [First step: Reaction (a) or reaction (b)] CF.

(X) Cl OR' In each of the above formulas, 2% R1, R2 and R3 are as defined above, R' is lower alkyl, and L is a leaving group.

Hereinafter, the first to third steps will be explained in more detail.

First step: In the step of reaction (a), the 3-(substituted aryloxy)benzoic acid ester derivative (III) and the sulfurizing agent (T
Compound (V) is prepared by reacting V) in an inert solvent.
).

As the sulfurizing agent (IV), for example, 2,4-bis(4-
Methoxyphenyl)-1,3-dithia-2.4-diphosphethane-2,4-disulfide, diethyldithiophosphate, phosphorus trisulfide, and the like can be used.

The reaction is carried out using generally 1 to 50 mol, preferably 1 to 20 mol, of the sulfurizing agent (IV) per 1 mol of compound (■), usually at room temperature to the reflux temperature of the solvent, preferably at a temperature within the range of room temperature to about 150 degrees Celsius. This is usually carried out for 1 hour to 10 days, preferably for 3 hours to 7 days.

Examples of inert solvents that can be used in this reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran and dioxane; chlorobenzene and acetonitrile.

After the reaction is completed, for example, the solvent is distilled off and then treated with column chromatography, or a nonpolar solvent such as pentane, hexane, petroleum ether, etc. is added to the reaction mixture to form a precipitate, and the filtrate is concentrated. The compound of formula (V) can be isolated with sufficient purity by such methods.

In the step of reaction (b), the 3-(substituted aryloquine)benzoic acid amide derivative (II) and phosgene are reacted in an inert solvent to obtain the imidoyl chloride salt (X), which is then reacted with a lower alcohol. Thereafter, the compound (V) of the present invention can be produced by reacting hydrogen sulfide in the presence of a base.

Reaction (a) shown in reaction (b) above uses 1 to 30 mol of phosgene, preferably 2 to 20 mol, per 1 mol of compound ([), and is usually from room temperature to the reflux temperature of the solvent, preferably from room temperature to about 100°C. Usually 1 hour to 10 minutes at a temperature within the range of
It is carried out for a period of 3 hours to 7 days, preferably for 3 hours to 7 days.

Examples of inert solvents that can be used in this reaction include halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; aromatic hydrocarbons such as benzene, toluene, and xylene; and ethers such as tetrahydro7rane and dioxane. It will be done.

After the completion of the reaction, intermediate (X) can be isolated,
The next reaction (b) is carried out using a normal solvent and the residue from which excess phosgene has been distilled off.

Reactions (b) and (c) can usually be carried out successively in the same solvent and in the same reaction vessel.

Reaction (b) uses 1 to 10 mol, preferably 1 to 2 mol, of lower alcohol per 1 mol of compound (X), and usually about -5 mol of lower alcohol.
The reaction is carried out at a temperature ranging from 0°C to the reflux temperature of the solvent, preferably from about -20°C to room temperature, usually for 1 minute to 1 day, preferably for 5 minutes to 1 hour.

As the base used in reaction (c), for example, triethylamine, pyridine, 2,6-lutidine, diazabicycloundecene, etc. can be used. The base is used in an amount of 1 to 20 mol, preferably 2 to 1 mol, per 1 mol of compound (XI).
0 mol is used, and hydrogen sulfide is 1 to 1 mol per mol of compound (XI).
50 mol, preferably 1 to 20 mol, usually about -50°
C to the reflux temperature of the solvent, preferably from about -20 C to room temperature, usually for 1 minute to 1 day, preferably for 5 minutes to 1 hour.

Examples of inert solvents that can be used in this reaction include halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, and mixed solvents thereof. Can be mentioned.

After the reaction is completed, the compound of the present invention can be isolated with sufficient purity by carrying out a usual post-treatment and then distilling off the excess base.

The second step, the Niki step, is a compound (■ ).

In the reaction, hydroxylamine (
VI) is generally used from 1 to 5 mol, preferably from 1 to 2 mol, under ice cooling to 200°C, preferably from room temperature to 120°C.
The heating is carried out at a temperature within the range of 30°C for usually 5 minutes to 10 days, preferably 15 minutes to 3 days.

Solvents used in this reaction include, for example, alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ether, tetrahydro7rane, and dioxane; dichloromethane, chloroform, and tetrachloride. Examples include halogenated hydrocarbons such as carbon, organic solvents such as niacetonitrile, dimethylformamide, and dimethyl sulfoxide, and mixed solvents of these solvents and water.

In addition, when preparing a solution of hydroxylamine (VI), when using salts such as hydroxylamine hydrochloride, sulfate, and oxalate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, acetic acid Pretreatment with a base such as sodium, potassium acetate, sodium methoxide, sodium ethoxide is advantageous.

After completion of the reaction, the compound of formula (■) is isolated by treating the reaction mixture according to a conventional method such as distilling off the solvent, extraction with water and an organic solvent, recrystallization, column chromatography, etc. Can be done.

The third step, the Niki step, involves reacting the 3-(substituted aryloxy)benzohydroxymic acid O-alkyl ether derivative (■) obtained in the second step with the compound (■) in an organic solvent in the presence of a base. This is a step for producing compound (I), which is a starting material for the method of the present invention.

The reaction is generally carried out using 1 compound (■) per mol of compound (■).
~5 mol, preferably 1 to 3 mol, is used, and the reaction is usually carried out at a temperature ranging from -50°C to the reflux temperature of the solvent, preferably from lO'C to about 80°C, for usually 0.5 to 20 hours.

The leaving groups in the above compound (■) include chlorine,
Bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group,
A triple olomethanesulfonyloxy group can be exemplified.

Solvents that can be used in the above reaction include, for example, alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as tetrahydrofuran and dioxane; halogenated hydrocarbons such as chloroform and methylene chloride; Acetone, acetonitrile, dimethylpolamide, dimethyl sulfoxide,
Examples include organic solvents such as N-methylpyrrolidone and mixed solvents of these solvents and water.

Examples of bases that can be used include sodium methoxide, sodium ethoxide, sodium hydride, potassium t-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and the like.

Furthermore, the above reaction can also be carried out in a two-layer system, in which case quaternary ammonium salts such as tetrabutylammonium bromide, benzyltributylammonium chloride, benzyltriethylammonium chloride, quaternary phosphonium salts such as benzyltriphenylphosphonium bromide, etc. It is convenient to use a phase transfer catalyst such as a salt in an amount of 1 to 60% by weight, preferably 1 to 5 to 40% by weight, based on compound (■).

After completion of the reaction, the compound of formula (I) can be isolated by pouring the reaction mixture into water and treating it according to conventional methods such as extraction with an organic solvent, recrystallization, and column chromatography.

Next, the method of the present invention will be explained in more detail with reference to Examples.

Methyl O-methquinecarbonylmethyl 3-(2-chloro-4-trifluoromethylphenoxy)benzohydroxymate 0.47 g (I, 12 mmol) (S
yn type: Anti type - about 4 = 6) dichloroethane (0
, 71mQ) solution was added with 1.31 g of sulfuric acid at -10°C, potassium nitrate was added little by little to the resulting solution at -2°C to 5°C, and the mixture was further stirred at the same temperature for 2 hours. Pour the reaction mixture into 10 mQ of ice water and add 10 mQ of dichloromethane.
The extract was extracted twice, washed with water and saturated brine in that order, and dried over magnesium sulfate. After filtering off the desiccant, the solvent is distilled off to obtain an oily substance (Syn type:Anti type=about 10:l
) was crystallized from methanol to obtain the target compound No. 1 (yield: 0.36 g, yield: 70%, Syn type only).

Compounds of formula (H) shown in Table 1 below were synthesized in the same manner as in the above examples.

Reference example: Production of compound of formula (r) Methyl 3-(2-chloro-4-trifluoromethylphenoxy)benzoate 24.4 g (0°074 mol)
was dissolved in xylene 80rxQ, and 400 g (0,099
After adding mol), the mixture was stirred at reflux temperature for 20 hours, and xylene was distilled off. The resulting residue was subjected to column chromatography (silica gel/n-hexane-ether 98:2).
The target compound Va was obtained (yield: 23°0g1).
yield 90%).

4.2 g (0,0122 mol) of amide was added to a methylene chloride solution (26 m(2)) containing 8.2 g of phosgene at room temperature, and the mixture was stirred at the same temperature for 18 hours to distill off excess phosgene and methylene chloride. The resulting residue was diluted with methylene chloride 2
Dissolve in 6mQ and add 0.59g of ethanol (0,012
8 mol) in THF solution (2omQ) at 5-10°C. Stir at the same temperature for 30 minutes after the dropwise addition, and add 5 to 1
While dropping 4.3 mQ (0,0532 mol) of pyridine at 0°C, hydrogen sulfide was blown into the mixture until it was saturated. After further stirring at the same temperature for 15 minutes, the solvent was distilled off and 30 ra of water was added.
Q was added thereto, extracted three times with ether 30IIIQ, and dried over magnesium sulfate. After filtering off the desiccant, the solvent and pyridine were distilled off to obtain the target compound Vf (yield: 4.0 g, yield: 91%).

The following table-2 was prepared using the same method as (A) and (A') above.
A compound of formula (V) shown below was synthesized.

N,N-dimethyl-3-(3-chloro-5-trifluoromethyl-2-pyridyloxy)penz(B) Methyl 3-(2-chloroo-4-trifhydroxylamine hydrochloride 1.53g (0, 022 mol) in methanol 2
4.24 g (0,022 mol) of 28% sodium methoxide/methanol solution was added under ice cooling. After stirring at the same temperature for 15 minutes, the mixture was filtered under suction to obtain a methanol solution of hydroxylamine.

6.59 g (0,01
The previously obtained methanol solution of hydroxylamine was added to a methanol (I5+++Q) solution of 9 mol), and the mixture was stirred at reflux temperature for 1.5 hours. The oily mixture obtained by distilling off the solvent was purified by column chromatography (silica gel/n-hexane-ethyl acetate 4; I) to obtain the desired compound (a).
(yield 5.56g, yield 85% Syn:An
ti-about 4=6).

This was roughly coated with column chromatography (silica gel/
Ant
The i-form (compound ①b) and the Syn-form (compound ①C) could be obtained.

Using the same method as in (B) above, the formula (■
) was synthesized.

(C) Methyl O-methoxycarbonylmethylmethyl 3-(2-chloro-4-trifluoromethylphenoxy)benzohydroxymate 3°46 g (0.01 mol) in DMF (30 m(I) solution, sodium hydride ( 60% in oil) 0.44g (0,011
After adding methyl bromoacetate (168 g (0,011
mol) was added at room temperature, and the mixture was further stirred at room temperature for 3 hours. Pour the reaction mixture into 60 mQ of ice water and add 40 mQ of ether.
The extract was extracted twice, washed with saturated brine, and dried over magnesium sulfate. After filtering off the desiccant, the solvent was distilled off and the resulting oily substance was subjected to column chromatography (silica gel/n-
Hexane-ethyl acetate 5:1) to obtain the target compound Ia (yield: 3.8 g, yield 91%, Syn:An
ti-about 4=6).

This was further subjected to column chromatography (silica gel/
By carefully purifying with n-hexane-chloroform (2=3), Anti-form (Compound Ib) and Syn-form (Compound Ic) could be obtained.

The formula (I
) was synthesized.

Claims (1)

[Claims] Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・(
I) In the formula, Z is CX or a nitrogen atom, where X is hydrogen or a halogen atom, R^1 and R^3 are each a lower alkyl group, and R^2 is a hydrogen atom or a lower alkyl group. The formula (
II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・(I
I) A method for producing a 2-nitro-5-(substituted aryloxy)benzohydroxymic acid derivative represented by the formula, wherein Z, R^1, R^2 and R^3 are as defined above.