KR0163206B1 - Process for producing an aromatic compound by electrophilic reaction and aromatic compound derivatives - Google Patents

Abstract

In order to selectively introduce a substituent into an aromatic ring, a process for preparing an aromatic compound of formula (I) and a novel compound prepared therefrom are disclosed, wherein a chelating reagent is reacted with a compound of formula (II) shown below. have :

[Wherein X ¹ and X ² are halogen atoms which may be the same or different: R is the following formula:

Wherein R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group:

Z is a cyano group, -CO-OR ³ (wherein R ³ is a hydrogen atom or a lower alkyl group) or -CO-N (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different, and hydrogen Is an atom or a lower alkyl group, and R ⁴ and R ⁵ together may represent an alkylene group).

Y is a nitro group, a halogen atom, a haloalkyl group or the following formula:

(Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group);

Description

Method for producing aromatic compound by electrolytic reaction and aromatic compound derivative

The present invention relates to a process for the preparation of an aromatic compound of the general formula (I), characterized by reacting a chelating reagent with a compound of the general formula (II), and an aromatic derivative thus prepared.

[Wherein, X ¹ and X ² are halogen atoms which may be the same or different;

R is the following formula:

Wherein R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group; Z is a cyano group, -CO-OR ³ (wherein R ³ is a hydrogen atom or a lower alkyl group) or -CO-N Represented by (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different and may be a hydrogen atom or a lower alkyl group, and R ⁴ and R ⁵ may be bonded together to represent an alkylene group). It is a group;

Y is a nitro group, a halogen atom, a haloalkyl group or the following formula:

(Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group);

[Wherein X ¹ , X ² and R have the same meaning as defined above.]

The celestial substitution reaction on the benzene ring has long been known, but selectively obtains 1, 2, 4, 5-substituted benzene derivatives of the general formula (I) from the compounds of the general formula (II) used in the present invention. There is no known way to do this.

Rec. Trav. Chim., 75, 190 (1956) discloses the following method.

When using this method, a substituent cannot be introduced at the desired substitution position and the methoxy group is converted to a hardoxy group. That is, the compound formed by the selective introduction of a substituent into the substitution position corresponding to general formula (I) which represents the compound obtained by this invention cannot be obtained.

The inventors have diligently studied a method for selectively introducing a substituent into an aromatic ring, and as a result, the present invention has been completed. Aromatic compounds of general formula (I) obtained by the preparation method of the present invention are useful as intermediates such as drugs, pesticides, chemicals, and the like, and some of them are novel.

As used herein, the term lower alkyl group or the like refers to a group having 1 to 6 carbon atoms.

The manufacturing method of the aromatic compound of general formula (I) of this invention is demonstrated in detail below.

① nitration reaction

This reaction can produce the aromatic compound of the following general formula (I-1) by selectively nitrating a compound of the general formula (II) with a nitrating agent in the presence of an inert solvent.

[Wherein X ¹ , X ² and R have the same meaning as defined above]

As the inert solvent usable in the present invention, any solvent can be used as long as it does not significantly inhibit the progress of the reaction. For example, nitric acid, sulfuric acid, acetic acid, trifluoroacetic acid and trifluoromethanesulfonic acid are mentioned. These inert solvents may be used alone or in a mixture thereof.

As the nitrating agent, for example, nitric acid, nitric acid-sulfuric acid, fuming nitric acid, fuming nitric acid-sulfuric acid, nitric acid-acetic acid, nitric acid-acetic anhydride, nitric acid-trifluoroacetic acid, and nitric acid-trifluoromethanesulfonic acid can be used. .

The amount of nitrating agent used may be appropriately selected within the range of 1 mol to excess mol per mol of the compound of formula (II).

The reaction temperature may be selected in the range of -20 ° C to 150 ° C, preferably in the range of 0 ° C to 50 ° C.

Although the reaction time varies depending on the reaction temperature, the degree of reaction and the like, it may be selected within a range of several minutes to 100 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture containing the compound by conventional methods such as solvent extraction and, if necessary, purified by recrystallization or the like to prepare the desired compound.

② halogenation reaction

In this reaction, the aromatic compound of the general formula (I-2) can be produced by selectively halogenating the compound of the general formula (II) with a halogenating agent in the presence of an inert solvent.

[Wherein X ¹ , X ² and R have the same meaning as defined above and Y ¹ is a halogen atom.]

As the inert solvent usable in the present invention, any solvent may be used as long as it does not significantly inhibit the progress of the reaction. For example, halogenated hydrocarbons (e.g., dichloromethane, chloroform, carbon tetrachloride and dichloroethane), sulfuric acid, acetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, dimethylformamide, 1,3-dimethyl-2-imidazoli Dinon and sulfolane. These inert solvents may be used alone or as a mixture thereof.

As the halogenating agent, for example, chlorine, bromine, chlorine-bromine, bromine-aluminum chloride, bromine-iron, and bromine-silver sulfate can be used.

The amount of halogenating agent used may be appropriately selected within the range of 1 mole to an excess per mole of the compound of formula (II).

The reaction temperature may be selected within the range of 0 ° C to 150 ° C, preferably 20 ° C to 100 ° C.

The reaction time varies depending on the reaction temperature, the degree of reaction, and the like, but may be selected within a range of several minutes to 100 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture containing the compound by conventional methods such as solvent extraction and, if necessary, purified by recrystallization to prepare the desired compound.

③ Friedel-Krafts reaction

This reaction is carried out by reacting a compound of formula (II) with a compound of formula (III), (IV) or (V) with Lewis acid in the presence or absence of an inert solvent and with or without salt. The aromatic compound of -3) can be prepared.

[Wherein, X ¹ , X ² and R have the same meaning as defined above, Y ¹ is a haloalkyl group or the following formula:

(Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group), X ³ is a halogen atom and X ⁴ may be the same or different May or is a halogen atom]

This reaction proceeds in the presence or absence of an inert solvent. Examples of the inert solvent include nitro alkanes such as nitromethane and the like: halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, tetrachloroethane, dichloroethane and the like; Aromatic hydrocarbons such as nitrobenzene, etc .: amides such as N-methylpyrrolidone, N, N-dimethylformamide, etc .: urea, such as N, N, N ', N'-tetramethylurea, N, N-dimethylformamide, etc. Derivatives; Urea derivatives such as tetramethylurea, N, N-dimethylimidazolinone, etc .: Organic bases such as pyridine, triethylamine, etc .: Organic sulfur compounds such as carbon disulfide, dimethyl sulfoxide, sulfolane, etc .: Alcohols such as ethanol, ethylene glycol, etc. Nitriles such as acetonitrile, benzonitrile and the like, and organic phosphorus compounds such as phosphorus oxychloride and hexamethylphosphamide. These inert solvents may be used alone or in a mixture thereof.

Although not critical, the amount of the inert solvent is preferably 0.5 to 10 moles per mole of the compound of formula (II).

Salts usable in the present invention include, for example, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, lithium chloride, sodium bromide, potassium bromide, lithium bromide, ammonium salts (e.g. tetramethylammonium chloride) and sulfonates (e.g. tri Fluoro methanesulfonic acid sodium). These salts may be used alone or in a mixture thereof.

The amount of salt used may be appropriately selected within the range of 0.5 to 10 moles per mole of the compound of formula (II).

As the Lewis acid, Lewis acids such as AlCl ₃ , AlI ₃ , FeCl ₃ , FeBr ₃ , TiCl ₄ , SnCl ₄ , ZnCl ₂ , GaCl _3, and the like may be used.

The amount of Lewis acid used may be appropriately selected within the range of 1 mol to excess mol per mol of the compound of formula (II), preferably 3 to 8 mol per mol of the compound.

The amount of the compound of formula (III), (IV) or (V) to be used may be appropriately selected within the range of 0.5 to 2 mol per mole of the compound of formula (II).

Compounds of general formula (V) may be used as reactants and as inert solvents. In this case, the compound may be used in large excess.

The reaction temperature may be selected within the range of 0 ° C to 180 ° C, preferably 60 ° C to 100 ° C.

The reaction time varies depending on the reaction temperature, the degree of reaction, and the like, but may be selected within a range of several minutes to 100 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture containing the compound by a conventional method such as solvent extraction, and, if necessary, purified by recrystallization or the like to prepare the target compound.

As mentioned above, some of the compounds prepared in this way are novel. That is, the aromatic compound represented by general formula (I) is new;

[Wherein, X ¹ and X ² are halogen atoms which may be the same or different; R is the following formula:

Wherein R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group, Z is a cyano group, -CO-OR ³ (wherein R ³ is a hydrogen atom or a lower alkyl group) or -CO-N Represented by (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different and are a hydrogen atom or a lower alkyl group, and R ⁴ and R ⁵ may be bonded together to represent an alkylene group). Group;

Y is a nitro group, a halogen atom, a haloalkyl group or the following formula;

(Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group), provided that when Y is a nitro group, X ¹ is a fluorine atom, and X is ² is a chlorine atom, Z is a cyano group or -CONR4R5, when Y is a fluorine atom, X ¹ is a fluorine atom, X ² is a chlorine atom, Z is a cyano group, and when Y is a chlorine atom, X ¹ is fluorine An atom, X ² is a chlorine atom, Z is -COOR ³ (where R 3 is a group other than a hydrogen atom), -CONR ⁴ R ⁵ or a cyano group].

In these, Y is a following formula;

(Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group) Japanese Patent Laid-Open No. 3-163063 (JP-A-3-163063 Useful as an intermediate for the preparation of the herbicides disclosed herein.

In particular, R is the following formula;

[Wherein, R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group, Z is —CON (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different and are a hydrogen atom Or a lower alkyl group, and R ⁴ and R ⁵ may be bonded together to represent an alkylene group.] Is very useful as an intermediate of the herbicide.

While typical embodiments of the invention are given below, they should not be construed as limiting the scope of the invention.

Example 1

Preparation of (2-Chloro-4-fluoro-5-nitrophenoxy) acetamide (Compound No. 1)

Dissolve 3.7 g (0.02 mole) of (2-chloro-4-fluorophenoxy) acetonitrile in 8 ml of 97% sulfuric acid and add 2.5 ml of mixed acid of 60-62% nitric acid and 5.8 ml 97% sulfuric acid. After addition to the solution obtained with stirring at 10 ° C. or lower, the reaction is carried out at room temperature for 1.5 hours.

After completion of the reaction, the reaction solution was poured into ice water and the precipitated crystals were collected by filtration, washed with water and dried to give 3.4 g of the target compound as yellow crude crystals (yield: 68%).

The crude crystal obtained is recrystallized from ethyl acetate to give 2.5 g of the target compound as pale yellow crystals.

Physical property: m.p. 182-182.5 ° C., yield: 50.5% NMR [DMSO / TMS, δ value (ppm)]

4.75 (s, 2H), 7.50 (bd, 2H, J = 0.6 Hz), 7.75 (d, 2H, J = 7 Hz), 7.97 (d, 2H, J = 11 Hz).

Example 2

Preparation of (2-Chloro-4-fluoro-5-nitrophenoxy) acetamide (Compound No. 1)

Same method as in Example 1, except using 4.1 g (0.02 mol) of (2-chloro-4-fluorophenoxy) acetamide in place of (2-chloro-4-fluorophenoxy) acetonitrile The reaction is carried out for 5 hours to yield 3.6 g of the target compound.

Yield: 72.4%

Example 3

Preparation of (2-Chloro-4-fluoro-5-nitrophenoxy) acetic acid (Compound No. 2)

In the same manner as in Example 1, 4.6 g (0.02 mole) of ethyl (2-chloro-4-fluorophenoxy) acetate was reacted and then left at room temperature overnight.

After completion of the reaction, the reaction solution containing the desired product is poured into ice water and the desired product is extracted with ethyl acetate.

The extracted solution is washed with water and dried over magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue obtained is purified by silica gel column chromatography (CH ₂ Cl ₂ —CH ₃ OH) to afford 1.3 g of the desired compound as ocher crystals.

Yield: 30.2%

NMR [DMSO / TMS, δ value (ppm)]

4.57 (s, 2H), 7.50 (bd, 2H, J = 0.6 Hz), 7.75 (d, 2H, J = 7 Hz), 7.97 (d, 2H, J = 11 Hz), 13.90 (bs, 1H).

Example 4

Preparation of (5-Bromo-2-chloro-4-fluorophenoxy) acetonitrile (Compound No. 3)

1.0 g (7.5 mmol) of anhydrous aluminum chloride is suspended in 10 ml of methylene chloride, 1.0 g (5.4 mmol) of (2-chloro-4-fluorophenoxy) acetonitrile is added to the suspension, followed by 0.95 g ( 5.9 mmol) bromine is added dropwise under reflux. After completion of the addition, the reaction is carried out under reflux for 2 hours.

After completion of the reaction, the reaction mixture is cooled and then poured into ice water and the desired compound is extracted with ether.

The extracted solution is washed successively with water, 10% aqueous sodium thiosulfate solution and saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent is then distilled off under reduced pressure and the residue obtained is recrystallized from n-hexane to give 1.1 g of the target compound.

Physical property: m.p. 72.3 ° C, yield 77%

Example 5

Preparation of (2-chloro-5-chloroacetyl-4-fluorophenoxy) acetamide (Compound No. 6)

2.0 g (15.0 mmol) of anhydrous aluminum chloride and 0.85 g (7.5 mmol) of chloroacetyl chloride are mixed and the resulting mixture is heated to 80 ° C. 1.0 g (4.9 mmol) of (2-chloro-4-fluorophenoxy) acetamide is then added and the reaction is carried out at 90 ° C. for 9 hours.

After completion of the reaction, the reaction mixture is cooled to 80 ° C. and 5 ml of acetic acid are added. The mixture thus obtained is poured into ice water and the precipitated crystals are filtered off and recrystallized from ethanol to obtain 1.0 g of the target compound.

Physical property: m.p. 166.3 ° C, yield 73%

Example 6

Preparation of (2-chloro-5-dichloroacetyl-4-fluorophenoxy) acetamide (Compound No. 7)

2.0 g (15.0 mmol) of anhydrous aluminum chloride and 0.93 g (6.3 mmol) of dichloroacetyl chloride are mixed and the resulting mixture is heated to 50 ° C. Next, 1.0 g (4.9 mmol) of (2-chloro-4-fluorophenoxy) acetamide is added, and the reaction is carried out at a reaction rate of 70 to 80 ° C. for 8 hours.

After completion of the reaction, the reaction mixture is cooled, ice-water is added and stirred for 2 hours. The desired compound is extracted with ethyl acetate and the extracted solution is washed with water and dried over magnesium sulfate. The ethyl acetate is then distilled off under reduced pressure and the residue obtained is purified by silica gel column chromatography to yield 0.5 g of the desired compound.

Physical property: m.p.132.3 ℃, yield 33%

Example 7

Preparation of (2-chloro-5-chloroacetyl-4-fluorophenoxy) acetonitrile (Compound No. 11)

2.0 g (15.0 mmol) of anhydrous aluminum chloride and 0.85 g (7.5 mmol) of chloroacetyl chloride are mixed and the resulting mixture is heated to 60 ° C. Then 0.9 g (4.0 mmol) of (2-chloro-4-fluorophenoxy) acetonitrile are added and the reaction is carried out at 70 ° C. for 3 hours.

After completion of the reaction, the reaction mixture is poured into ice water and stirred for 1 hour. The precipitated crystals are collected by filtration and recrystallized from ethanol to obtain 0.93 g of the target compound.

Physical property: m.p.122.1 ℃, yield 73%

Example 8

Preparation of (2-chloro-5-dichloroacetyl-4-fluorophenoxy) acetonitrile (Compound No. 13)

2.0 g (15.0 mmol) of anhydrous aluminum chloride and 0.93 g (6.3 mmol) of dichloroacetyl chloride and 0.9 g (4.9 mmol) of (2-chloro-4-fluorophenoxy) acetonitrile were mixed and at 60 ° C. The reaction is carried out for 2 hours.

After completion of the reaction, the reaction mixture is cooled and 5 ml of nitromethane are added. After pouring the obtained mixture into ice water, the desired compound is extracted with ethyl acetate and the extracted solution is washed with water and dried over magnesium sulfate. The solvent is then distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography to yield 0.97 g of the desired compound.

Material Properties: m.p.98.7 ℃, Yield 67%

Example 9

Preparation of (2-Chloro-4-fluoro-5-trichloromethylphenoxy) acetonitrile (Compound No. 14)

Suspend 1.5 g (11.2 mmol) of anhydrous aluminum chloride in 10 ml of carbon tetrachloride and add 1.0 g (5.4 mmol) of (2-chloro-4-fluorophenoxy) acetonitrile dropwise. After the addition is complete, the reaction is carried out at 60 ° C. for 1 hour.

After completion of the reaction, the reaction mixture is cooled, ice water is added and stirred for 1 hour. The desired compound is extracted with ethyl acetate and the extracted solution is washed with water and dried over magnesium sulfate. The solvent is then distilled off under reduced pressure and the residue obtained is purified by silica gel column chromatography to yield 1.2 g of the desired compound as an oil.

Physical properties: Oil, yield 72%

NMR [CDCl 3 / TMX, δ value (ppm)]

4.88 (s, 2H), 7.09 (d, 1H, J = 10.4 Hz), 7.79 (d, 1H, J = 7.1 Hz).

Example 10

Preparation of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetonitrile (Compound No. 17)

To 4.5 g (33.6 mmol) of anhydrous aluminum chloride, 0.57 g (7.8 mmol) of dimethyl formamide (DMF) was added, and 1.0 g (5.6 mmol) of (2-chloro-4-fluorophenoxy) was added to the suspension. Acetonitrile is added at room temperature. Then, 2.9 g (28.0 mmol) cyano acetyl chloride is slowly added dropwise to the mixture obtained above. After completion of dropping, the reaction was carried out at 55 ° C. for 3 hours.

After completion of the reaction, the reaction mixture is analyzed by thin layer chromatography and gas chromatography (area: 7.0%). The analysis results obtained are consistent with the results obtained for the standard material, thereby confirming the preparation of the target compound.

The compound of general formula (I) is shown in Table 1.

Aromatic compound derivatives represented by formula (I ') are particularly important as intermediates in the preparation of herbicides disclosed in Japanese Patent Laid-Open No. 3-166063. Typical herbicides that are final products can be prepared, for example, by the methods illustrated below.

Wherein R, R ¹ , R ² , X and Y are as defined above, R ³ represents a lower alkoxy group, R ⁴ represents a lower alkyl group or a lower haloalkyl group, and R ⁵ represents a lower alkyl group or a lower halo Alkyl group, and Hal represents a halogen atom).

Claims (7)

A method for producing an aromatic compound represented by the following general formula (I), comprising reacting a compound represented by the following general formula (II) with an electrophilic reagent: [Wherein X ¹ and X ² are halogen atoms which may be the same or different: R is the following formula: Wherein R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group, Z is a cyano group, -CO-OR ³ (wherein R 3 is a hydrogen atom or a lower alkyl group) or -CO-N A group represented by (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different and are a hydrogen atom or a lower alkyl group, and R ⁴ and R ⁵ may be bonded together to represent an alkylene group) And Y is a nitro group, a halogen atom, a haloalkyl group or the following formula: (Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group) [Wherein X ¹ , X ² and R have the same meaning as defined above] The process for producing an aromatic compound according to claim 1, wherein the protic reagent is a nitrating agent. The method of claim 1, wherein the electrophilic reagent is a halogenating agent. The method of claim 1, wherein the protic reagent is Lewis acid and general formula (III): General formula (IV) Or general formula (V): C (X ⁴ ) ₄ [wherein, R ⁶ , R ⁷ and R ⁸ may be the same or different, a hydrogen atom, a halogen atom or a cyano group, X ³ is a halogen atom, X ⁴ may be the same or different It may be a halogen atom.] A method for producing an aromatic compound, characterized in that a combination of compounds represented by. Aromatic compounds represented by the following general formula (I): [Wherein X ¹ and X ² are halogen atoms which may be the same or different: R is the following formula: Wherein R 1 and R 2 may be the same or different and are a hydrogen atom or a lower alkyl group, Z is a cyano group, -CO-OR ³ (wherein R ³ is a hydrogen atom or a lower alkyl group) or -CO-N (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different and are a hydrogen atom or a lower alkyl group and R ⁴ and R ⁵ may be bonded together to represent an alkylene group); Y is a nitro group, a halogen Atom, haloalkyl group or the following general formula: (Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group), provided that when Y is a nitro group, X ¹ is a fluorine atom, X ² is a chlorine atom, Z is a cyano group or -CONR ⁴ R ⁵ ; When Y is a fluorine atom, X ¹ is a fluorine atom, X ² is a chlorine atom and Z is a cyano group; When Y is a chlorine atom, X ¹ is a fluorine atom, X ² is a chlorine atom, Z is -COOR ³ (where R 3 is a group other than a hydrogen atom), -CONR ⁴ R ⁵ or a cyano group. The method of claim 5, wherein Y is represented by the following formula: [Wherein R ⁶ , R ⁷ and R ⁸ may be the same or different and are a hydrogen atom, a halogen atom or a cyano group]. The compound of claim 6, wherein R in the compound is represented by the following formula; [Wherein, R ¹ and R ² may be the same or different and are a hydrogen atom or a lower alkyl group, Z is —CON (R ⁴ ) R ⁵ (wherein R ⁴ and R ⁵ may be the same or different, and hydrogen An atom or a lower alkyl group, and R ⁴ and R ⁵ may be bonded together to represent an alkylene group.