JPH0687787A - Aromatic ester derivative, its intermediate and their production - Google Patents

Abstract

PURPOSE:To provide a new derivative useful as an intermediate for pharmaceuticals, agricultural chemicals, chemicals, etc. CONSTITUTION:The derivative of formula I (R<1> to R<4> are H or lower alkyl; R<5>' is lower alkyl; X is halogen; m is 0-4), e.g. ethyl(4chloro-5- ethoxycarbonylmethoxy-2-fluorobenzoyl)acetate. The compound of formula I can be produced e.g. by reacting a compound of formula II (Z is cyano or CONH2) with an alcohol of the formula R<5>'-OH in the presence of an acidic substance (e.g. hydrochloric acid or hydrogen chloride gas) in the presence or absence of an inert solvent (e.g. dichloromethane or benzene) preferably at 0-100 deg.C and hydrolyzing the reaction product at pH4 or below.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the general formula (I)

[Chemical 27] [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, R ⁵ 'is a lower alkyl group, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The present invention relates to an aromatic ester derivative represented by the formula, an intermediate thereof, and a method for producing them.

[0002]

2. Description of the Related Art A method for producing aromatic esters has been known for a long time, for example, Sandler and Karo "Organic Func.
tional Group Preparations "Vol. 13, p268-281 (1972)
Etc.

[0003]

The present inventors have completed the present invention as a result of earnest studies on a method for producing an aromatic ester by solvolysis, and as a result, the aroma according to the production method of the present invention has been obtained. Group esters are compounds useful as intermediates for medicines, agricultural chemicals, chemicals and the like.

[0004]

The method for producing the aromatic ester derivative represented by the general formula (I) of the present invention can be exemplified by the method shown below.

[Chemical 28] [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ', X, m and Z are the same as defined above. ]

1. General formula (V) → General formula (I) This reaction is represented by the general formula (IV) in the presence of an acidic substance, in the presence or absence of an inert solvent, of the compound represented by the general formula (V). The compound represented by the general formula (I) can be produced by reacting with an alcohol, and then hydrolyzing at a pH of 4 or less.

The inert solvent which can be used in this reaction may be any one which does not markedly hinder the progress of this reaction, for example, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, benzene, toluene, xylene and chlorobenzene. Examples thereof include aromatic hydrocarbons such as dioxane, diglyme, sulfolane, acetic acid and trifluoroacetic acid, and these inert solvents can be used alone or in a mixture.

Examples of the acidic substance used in the present invention include hydrochloric acid, sulfuric acid, hydrogen chloride gas, hydrogen bromide gas, hydrogen iodide gas and the like. The amount of these acidic substances used is represented by the general formula ( The compound represented by V) may be appropriately selected from the equimolar to excess molar range and used.

The amount of the alcohols represented by the general formula (IV) is preferably equimolar or more with respect to the compound represented by the general formula (V). Reaction temperature is -20 ° C to 150 ° C
The reaction may be carried out by selecting from the range of, preferably 0 ° C to
It is in the range of 100 ° C. Although the reaction time is not constant depending on the reaction temperature, the reaction scale, etc., it may be selected from the range of several minutes to 150 hours.

The hydrolysis reaction may be carried out according to a conventional method.
After the completion of the reaction, the desired product can be produced by isolating it from the reaction system containing the desired product by a conventional method, for example, solvent extraction and the like, and purifying it by recrystallization or the like if necessary.

2. General formula (II) → general formula (I) This reaction is represented by general formula (IV) in the presence of an acidic substance, in the presence or absence of an inert solvent, a compound represented by general formula (II) General formula (I)
Aromatic esters represented by can be produced.
As the inert solvent and the acidic substance that can be used in this reaction, for example, the inert solvent and the acidic substance exemplified in 1 can be used, and the amount of the acidic substance to be used is relative to the compound represented by the general formula (II). It may be used by appropriately selecting from the range of equimolar to excess molar.

The alcohol represented by the general formula (IV) is preferably used in an equimolar amount or more with respect to the compound represented by the general formula (II), but may be used in a smaller amount. The reaction temperature may be selected from the range of −20 ° C. to 150 ° C. for the reaction. Although the reaction time is not constant depending on the reaction temperature, the reaction scale, etc., it may be selected from the range of several minutes to 150 hours. After completion of the reaction, the aromatic ester derivative represented by the general formula (I) can be produced by isolation from the reaction system containing the desired product by a conventional method.

3. General formula (III) → General formula (I) This reaction is represented by the general formula (IV) in the presence of an acidic substance, in the presence or absence of an inert solvent, the compound represented by the general formula (III) The aromatic ester represented by the general formula (I) can be produced by reacting with an alcohol of the formula (I) and then hydrolyzing at a pH of 4 or less. Each of these reactions is 1
The aromatic ester represented by the general formula (I) can be produced in the same manner as in. The compound represented by the general formula (II) obtained in this reaction can be isolated after the completion of the reaction, or can be used in the next reaction without isolation.

4. General formula (III) → general formula (II) This reaction is represented by general formula (II) by reacting the compound represented by general formula (III) with an acidic substance in the presence or absence of an inert solvent. The compound can be prepared.
As the inert solvent and the acidic substance that can be used in this reaction, for example, the inert solvent and the acidic substance described in 1 can be used.

The reaction temperature may be selected from the range of -20 ° C to 150 ° C to carry out the reaction. Although the reaction time is not constant depending on the reaction temperature, the reaction scale, etc., it may be selected from the range of several minutes to 150 hours. After completion of the reaction, the compound represented by the general formula (II) can be produced by isolation from the reaction system containing the desired product by a conventional method. The compound represented by the general formula (II) obtained in this reaction can be used in the next reaction without isolation.

5. General formula (III '') → general formula (II) This reaction is carried out by reacting the compound represented by general formula (III '') with general formula (I) in the presence or absence of an inert solvent and in the presence of an acidic substance.
The compound represented by the general formula (II) can be produced by reacting with the alcohol represented by V). As the inert solvent and acidic substance that can be used in this reaction, for example, the inert solvent and acidic substance described in 1 can be used.
The amount of alcohol represented by the general formula (IV) is determined by the general formula (I
It is preferable to use the compound represented by II ″) in an equimolar amount or more.

The reaction temperature may be selected from the range of -20 ° C to 150 ° C to carry out the reaction. Although the reaction time is not constant depending on the reaction temperature, the reaction scale, etc., it may be selected from the range of several minutes to 150 hours. After completion of the reaction, the compound represented by the general formula (II) can be produced by isolation from the reaction system containing the desired product by a conventional method. The compound represented by the general formula (II) obtained in this reaction can be used in the next reaction without isolation.

6. General formula (V '') → general formula (III) This reaction is carried out by reacting a compound represented by general formula (V '') with an acidic or basic substance in the presence or absence of an inert solvent. Reaction with alcohols of formula (IV), then p
The compound represented by the general formula (III) can be produced by hydrolysis under H4 or less. As the inert solvent that can be used in this reaction, for example, in addition to the inert solvent that can be used in 1, dimethylformamide, N-methylpyrrolidone and the like can be used.

As the acidic substance, in addition to the acidic substance exemplified in 1, acetic acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like can be used. As the basic substance, for example, an alcoholate of an alkali metal atom such as sodium or potassium can be used, and the basic substance is preferably used in this reaction, but the basic substance is not limited thereto. This reaction can be carried out in the same manner as in 1 using the above-mentioned inert solvent and acidic or basic substance to produce the compound represented by the general formula (III). The compound represented by the general formula (III) obtained in this reaction can be isolated after the completion of the reaction, or can be used in the next reaction without isolation.

7. General formula (V ') → general formula (III) This reaction is carried out by reacting the compound represented by the general formula (V') with the general formula (V in the presence or absence of an inert solvent in the presence of an acidic or basic substance. The compound represented by the general formula (III) can be produced by reacting with the alcohol represented by IV). As the inert solvent, the acidic substance and the basic substance which can be used in this reaction, for example, the inert solvent, the acidic substance and the basic substance which can be used in 6 can be used. This reaction is carried out in the same manner as in 3 using the above-mentioned inert solvent and acidic or basic substance to produce the compound represented by the general formula (III). The general formula (I
The compound represented by II) can be isolated after the completion of the reaction, or can be used in the next reaction without isolation.

8. General formula (V ') → general formula (III'') This reaction is carried out by reacting the compound represented by the general formula (V') with an acidic substance in the presence or absence of an inert solvent. III ″) can be produced. This reaction is carried out in the same manner as in the general formula (III '')
A compound represented by can be produced. The compound represented by the general formula (III ″) or represented by this reaction can be isolated after the completion of the reaction, or can be used in the next reaction without isolation.

When R ⁵ represents a hydrogen atom in the compounds represented by the general formulas (II ′) and (III ′), it can be produced by the following production method.

[Chemical 29] (In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above, and Hal represents a halogen atom, provided that R ⁵ ′ does not include a lower alkyl group.)

The compound represented by the general formula (VI ′) is reacted with an acidic substance in the presence or absence of an inert solvent to give a compound represented by the general formula:
(VI '') as a compound, and the compound (VI '') is isolated, or is not isolated in the presence of an inert solvent or in the absence of a reaction with a cyanating agent in the general formula (III '), the compound (III') is isolated, or without isolation in the presence of an inert solvent, or by reacting with an acidic substance in the absence of the general formula ( The compound represented by II ′) can be produced.

9. General formula (VI ')-> General formula (VI'')-> General formula (III') In the first step, the alcohol represented by general formula (IV) is not used, The general formula (VI '') can be prepared. The inert solvent that can be used in the second cyanation step may be any one that does not significantly impede the progress of this reaction, and examples thereof include water, methanol, ethanol, alcohols such as propanol, and the like. Nitriles such as acetonitrile, diethyl ether, tetrahydrofuran, ethers such as dioxane, ethylene glycol, glycols such as propylene glycol, methyl cellosolve, cellosolves such as ethyl cellosolve, pyridine, picoline, Examples thereof include dimethylformamide, acetamide, dimethylsulfoxide, hexamethylenetetraamide, hexamethylphosphoramide, N, N'-dimethylimidazolinone, etc. These inert solvents may be used alone or in combination. You can

Examples of the cyanating agent used in this reaction include sodium cyanide, potassium cyanide, calcium cyanide, copper cyanide, ammonium cyanide, triethylammonium cyanide, tetrabutylammonium cyanide, acetocyanhydrin and the like. A cyanating agent can be mentioned, and the amount thereof can be selected from the range of equimolar to excess molar to the compound represented by the general formula (VI ″), preferably equimolar to 5-fold molar. Is the range.

When a base is used in this reaction, an inorganic base or an organic base can be used, and examples thereof include sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydride, and hydroxide. Inorganic bases such as sodium, potassium hydroxide, lithium carbonate, lithium hydroxide, sodium acetate, trisodium phosphate, tripotassium phosphate, sodium borate and potassium borate, and primary amines such as ethylamine and t-butylamine. , Secondary amines such as diethylamine, diisopropylamine, trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, N, N-diisopropylethylamine, N, N-dimethyl-n-octylamine, triethano- Luamine,
N-methylpiperidine, 1,4-diazabicyclo [2,2
2,2] tertiary amines such as octane, aniline, N,
Aromatic amines such as N-dimethylaniline, 2,6-lutidine, and pyridine can be exemplified, and the amount of these bases used is equimolar to excess with respect to the compound represented by the general formula (II). Although it can be appropriately selected and used from the molar range, a base may not be used.

As the acid that can be used in this reaction, for example, mineral acids such as hydrochloric acid and sulfuric acid, and organic acids such as acetic acid can be used, and the amount thereof is the compound represented by the general formula (VI ''). On the other hand, it may be selected from the range of equimolar to excess molar,
The amount is preferably equimolar to 4 times the molar amount, but when the cyanating agent used at the same time is used in excess, it is better to use it in an amount about 1 equivalent less than the amount of the cyanating agent used. As the inorganic salt that can be used in this reaction, for example, calcium chloride, magnesium chloride, sodium iodide, potassium iodide, etc. can be used, and the amount thereof is the same as that of the compound represented by the general formula (II). It can be appropriately selected and used from the range of mol to excess mol.

The reaction temperature may be selected from the range of -20 ° C to 150 ° C for the reaction, and preferably in the range of 0 ° C to 60 ° C. The reaction time varies depending on the reaction temperature, the reaction scale, etc., but may be selected from the range of several minutes to 100 hours. After the completion of the reaction, the reaction system containing the desired product is produced as it is or after being acidified with a mineral acid such as hydrochloric acid, and isolated by a conventional method, for example, filtration, solvent extraction and the like, and purified by recrystallization or the like, if necessary. can do.

10. General Formula (III ′) → General Formula (II ′) By performing this reaction in the same manner as in 4, the compound represented by General Formula (II ′) can be produced. General formula of the invention
The compound represented by the general formula (V), which is a starting compound for producing the aromatic ester represented by (I), can be produced, for example, by the method exemplified below.

[0029]

[Chemical 30] [In the formula, R ¹ , R ² , R ³ , R ⁴ , X, m and Z are the same as defined above, Hal represents a halogen atom, and n represents an integer of 0 to 3. ]

The phenols represented by the general formula (XI) are reacted with the halides represented by the general formula (IX) to give the general formula (VII
The compound represented by the general formula (VI) is obtained by separating the compound (VIII) with or without isolation.
I) or a compound represented by the general formula (XI) by selectively halogenating the phenols represented by the general formula (XI) to the compound represented by the general formula (X), ) Is isolated,
Alternatively, the compound represented by the general formula (VII) can be obtained by reacting with the halide represented by the general formula (IX) without isolation, and the compound (VII) can be isolated or isolated without isolation. −
A compound represented by the general formula (VI) is obtained by carrying out a Delcraft reaction, and the compound (VI) is isolated or is cyanated without isolation to produce a compound represented by the general formula (V). can do.

[0031]

EXAMPLES Representative examples of the present invention will be illustrated below, but the present invention is not limited thereto.

Example 1. Ethyl (4-chloro-5-
Production of ethoxycarbonylmethoxy-2-fluorobenzoyl) acetate 1-1.

[Chemical 31] 10 g of (4-chloro-5-cyanomethoxy-2-fluorobenzoyl) acetonitrile in 40 ml of toluene
(0.04 mol) and 5.5 g of ethanol were added, and hydrogen chloride was added to the solution at 15 to 20 ° C. for 4 hours (flow rate 40 ml /
(min), the blowing of hydrogen chloride was stopped, and the reaction was further continued for 2 hours. Then, 10% sodium hydroxide aqueous solution was added, and the reaction was carried out at 40 to 50 ° C. for 2 hours. After completion of the reaction, the reaction liquid containing the target substance is separated, 40 ml of toluene is further added to the aqueous layer to extract the target substance, and the organic layer separated previously is washed with water and dried over anhydrous magnesium sulfate. The crude crystal obtained by distilling off the solvent under reduced pressure was recrystallized from ether / n-hexane to obtain 13.5 g of the desired product as a brown crystal. Physical properties mp 40.0-41.5 ° C Yield 98.5
%

1-2.

[Chemical 32] 1.0 g (0.0037 mol) of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetamide was added to 4 ml of toluene and 1.7 g of ethanol, and hydrogen chloride gas was passed through the solution at 40 to 50 ° C. The reaction was carried out for 3.5 hours, then 40 ml of water was added and the reaction was carried out at the same temperature for 1 hour. After completion of the reaction, the reaction liquid containing the target substance is separated, 40 ml of toluene is further added to the aqueous layer to extract the target substance, and the organic layer separated previously is washed with water and dried over anhydrous magnesium sulfate. 1.2 g of the solvent was distilled off under reduced pressure.
Of brown oil was obtained. The obtained brown oily substance was purified by column chromatography to give 0.53 g of the desired product.
Got Yield 41%

1-3.

[Chemical 33] Ethyl (5-carbamoylacetyl-2-chloro-4-fluorophenoxy) acetate was added to 10 ml of ethanol.
2 g (6.3 mmol) and 1.2 g of concentrated sulfuric acid (12.
6 mmol) was added and the reaction was carried out under heating under reflux for 1.5 hours. After the reaction was completed, the reaction mixture was poured into ice water, the desired product was extracted with ether, washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.9 g of a residue. The obtained residue was purified by column chromatography to obtain 0.8 g of the desired product. Yield 37%

1-4.

[Chemical 34] 5.0 g (0.017 mol) of ethyl (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetate and 0.8 g of ethanol were added to 10 ml of toluene, and hydrogen chloride gas was added to the solution at 15%. After passing at -20 ° C for 3 hours (flow rate 20 ml / min), blowing of hydrogen chloride gas was stopped and the reaction was carried out at the same temperature for 20 hours.

After that, 10 ml of toluene and 20 ml of water
Was added and the reaction was carried out at 40 to 50 ° C. for 2 hours. After completion of the reaction, the reaction liquid containing the target substance is separated, and 20 ml of toluene is further added to the aqueous layer to extract the target substance. The target layer is combined with the previously separated organic layer, washed with water, and dried over anhydrous magnesium sulfate, The crude crystals obtained by distilling off the solvent under reduced pressure are treated with ether / n-
By recrystallizing from hexane, 5.5 g of the desired product was obtained as brown crystals. Physical properties mp 40.0-41.5 ° C Yield 93.6%

Example 2. Preparation of ethyl (5-carbamoylacetyl-2-chloro-4-fluorophenoxy) acetate

[Chemical 35] Ethyl (2-chloro-5
-Cyanoacetyl-4-fluorophenoxy) acetate-
20 g (66.7 mmol) was added and concentrated sulfuric acid 50 ml
Was added and the reaction was carried out on a water bath with stirring overnight. After the reaction was completed, the reaction solution was poured into ice water under vigorous stirring, and the precipitated crystals were collected by filtration, washed with water, and dried to obtain the desired product 19.
9 g was obtained. Physical properties mp125.0-126.5 ° C Yield 94%

Example 3. Preparation of ethyl (5-carbamoylacetyl-2-chloro-4-fluorophenoxy) acetate and ethyl (4-chloro-5-ethoxycarbonylmethoxy-2-fluorobenzoyl) acetate ethyl

[Chemical 36] 5 g (0.017 mol) of (5-carbamoylmethoxy-4-chloro-2-fluorobenzoyl) acetamide was suspended in 20 ml of ethanol, and the suspension was concentrated with sulfuric acid.2.
The reaction was carried out by adding 5 g and heating under reflux for 2 hours. After completion of the reaction, the reaction solution was cooled, and 30 ml of toluene and 30 ml of saturated saline were added to extract the target substance.

The crystals precipitated from the extract were collected by filtration, washed with water and dried to obtain 1.7 g of ethyl (5-carbamoylacetyl-2-chloro-4-fluorophenoxy) acetate. Physical properties mp125.0-126.5 ° C Yield 31% The filtrate was further concentrated, and the residue was purified by column chromatography to obtain ethyl (4-chloro-5-ethoxycarbonylmethoxy-2-fluorobenzoyl) acetate 2 Obtained 0.2 g. Physical properties mp 40.0-41.5 ° C Yield 37%

Example 4. Ethyl (2-chloro-5-
Preparation of cyanoacetyl-4-fluorophenoxy) acetate

[Chemical 37] 4-1. A solution prepared by dissolving 20 g (0.079 mol) of (4-chloro-5-cyanomethoxy-2-fluorobenzoyl) acetonitrile in 50 ml of N-methylpyrrolidone was added to a solution saturated with hydrogen chloride gas in 100 ml of ethanol. The mixture was dropped and reacted at room temperature for 2 hours. Then, the reaction solution was poured into 500 ml of ice water, the desired product was extracted with ethyl acetate, the extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. By purifying with ethyl acetate: n-hexane = 1: 2), 19.8 g of the desired product was obtained as pale yellow crystals. Physical property mp 83.5-85.5 ° C Yield 84%

4-2.

[Chemical 38] 90 mg (3.9 mmol) of sodium was added to 2 ml of ethanol, and 0.5 g of (4-chloro-5-cyanomethoxy-2-fluorobenzoyl) acetonitrile was added.
(2.0 mmol) was added and the reaction was carried out at room temperature for 3 hours. After completion of the reaction, the reaction solution was poured into ice water and acidified with hydrochloric acid, and the target product was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give the desired product (0.1%).
5 g was obtained. Physical property mp 83.5-85.5 ° C Yield 84%

4-3.

[Chemical Formula 39] (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetamide 10 in 100 ml of ethanol.
g (0.037 mol) and 5.4 g of concentrated sulfuric acid were added, and the reaction was performed for 2.5 hours while heating under reflux. Then, the reaction mixture was concentrated under reduced pressure and poured into 200 ml of ice water, the target product was extracted with ethyl acetate (150 ml × 2), the organic layer was washed with water and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue obtained by silica gel chromatography
Purification with (ethyl acetate: n-hexane = 1: 2) gave 10.1 g of the desired product as pale yellow crystals. Physical properties mp 83.5-85.5 ° C Yield 91.3%

Example 5. Preparation of (5-carbamoylmethoxy-4-chloro-2-fluorobenzoyl) acetamide

[Chemical 40] 5-1. 30 g (0.11 mol) of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetamide
120 g of concentrated sulfuric acid was added to the mixture and the reaction was carried out at room temperature for 6 hours. After the reaction was completed, the reaction solution was poured into ice water, and the precipitated crystals were collected by filtration, washed with water, and dried to obtain the desired product 31.2.
g was obtained. Physical properties mp204-205 ° C Yield 98%

5-2. 600 ml of concentrated sulfuric acid was added dropwise to a suspension of 200 g of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetamide and 400 ml of toluene under stirring at a reaction temperature of 10 to 25 ° C. for 30 minutes, and after completion of the addition, at room temperature. To react for 24 hours. After completion of the reaction, the reaction solution was gradually poured into 2 kg of ice with stirring, and 1 L (liter) of water was added to the precipitated crystals and the residue remaining in the reaction vessel, and the precipitated crystals were filtered and washed with water to obtain the crystals. Of the target compound 200 by drying under reduced pressure at 60 ° C. for 24 hours.
g was obtained.

Example 6. Production of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetic acid

[Chemical 41] 6-1. 50 g of (2-chloro-5-chloroacetyl-4-fluorophenoxy) acetamide and 150 ml of acetic acid
75 ml of concentrated hydrochloric acid was added and the mixture was reacted under reflux for 1 hour. Then, 75 ml of concentrated hydrochloric acid was added and cooled to room temperature. After the reaction was completed, the precipitated crystals were filtered and washed with water, and the obtained crystals were dried under reduced pressure at 50 ° C to obtain 44.6 g of the desired product. Physical properties mp 170-174 ° C Yield 89%

6-2. To a solution prepared by dissolving 0.26 g of sodium cyanide in 5 ml of water, 0.50 g of (2-chloro-5-chloroacetyl-4-fluorophenoxy) acetic acid obtained in 6-1 and 1.78 g of sodium carbonate were added in 20 ml.
The aqueous solution dissolved in water was added dropwise at room temperature, and after the addition was completed, the reaction was carried out at room temperature for 6 hours. After the reaction was completed, the reaction solution was acidified with 6N-hydrochloric acid (2 ml) to obtain hydrochloric acid and ethyl acetate (10 ml)
It was extracted with (× 3), and the extract was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to give pale brown crystals 0.45.
g was obtained. Physical properties mp186.8-192.3 ° C Yield 69%

Example 7. Production of (2-chloro-5-carbamoyl-4-fluorophenoxy) acetic acid

[Chemical 42] 50 g of concentrated sulfuric acid in 10 g (0.037 mol) of (2-chloro-5-cyanoacetyl-4-fluorophenoxy) acetic acid.
Was added and reacted at room temperature for 24 hours. After the reaction,
200 ml of ice water was poured into the reaction solution, and the precipitated crystals were filtered,
By drying, 9.6 g of the desired product was obtained. Physical properties mp 198.0-199.0 ° C (decomposition)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical indication C07C 253/30 255/40 9357-4H

Claims (12)

[Claims] 1. A compound represented by the general formula (I): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, R ⁵ 'is a lower alkyl group, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The aromatic ester derivative represented by these. 2. A general formula (V): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, m is an integer of 0 to 4, Z is a cyano group or -CONH ₂ . ] The compound represented by the general formula (IV) [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound represented by the general formula (I) is characterized in that it is reacted with an alcohol represented by [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above. ] The manufacturing method of the aromatic ester derivative represented by these. 3. A compound represented by the general formula (II): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, R ⁵ 'is a lower alkyl group, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by the general formula (IV) [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound represented by the general formula (I) characterized by reacting with an alcohol represented by [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above. ] The manufacturing method of the aromatic ester derivative represented by these. 4. A compound represented by the general formula (III): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, R ⁵ 'is a lower alkyl group, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by the general formula (IV) [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound represented by the general formula (I) is characterized in that it is reacted with an alcohol represented by (In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above.) A process for producing an aromatic ester derivative. 5. A compound represented by the general formula (II ′): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ may be the same or different and represent a hydrogen atom or a lower alkyl group, X may be the same or different and represent a halogen atom, m Represents an integer of 0 to 4. ] The compound represented by these. 6. A compound represented by the general formula (III ′): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ may be the same or different and represent a hydrogen atom or a lower alkyl group, X may be the same or different and represent a halogen atom, m Represents an integer of 0 to 4. ] The compound represented by the general formula (II ') characterized by reacting a compound with an acidic substance [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , X and m are the same as defined above. ] The manufacturing method of the compound represented by these. 7. A compound represented by the general formula (III ″): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by the general formula in the presence of an acidic substance
(IV) [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound of the general formula (II) characterized by reacting with an alcohol represented by [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above. ] The manufacturing method of the compound represented by these. 8. A compound represented by the general formula (III ′): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ may be the same or different and represent a hydrogen atom or a lower alkyl group, X may be the same or different and represent a halogen atom, m Represents an integer of 0 to 4. ] The compound represented by these. 9. A compound represented by the general formula (V ″): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by the general formula (IV) in the presence of an acidic or basic substance: [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound represented by the general formula (III) is characterized in that it is reacted with an alcohol represented by [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above. ] The manufacturing method of the compound represented by these. 10. A compound represented by the general formula (V ′): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] In the presence of an acidic or basic substance represented by the general formula (IV) [In the formula, R ⁵ 'represents a lower alkyl group. ] The compound of the general formula (III) characterized by reacting with an alcohol represented by [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ′, X and m are the same as defined above. ] The manufacturing method of the compound represented by these. 11. A compound represented by the general formula (III ″): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by these. 12. A compound represented by the general formula (V ′): [In the formula, R ¹ , R ² , R ³ and R ⁴ may be the same or different,
A hydrogen atom or a lower alkyl group is shown, X may be the same or different, a halogen atom is shown, and m is an integer of 0-4. ] The compound represented by the general formula (III '') characterized by reacting with an acidic substance [In the formula, R ¹ , R ² , R ³ , R ⁴ , X and m are the same as defined above. ] The manufacturing method of the compound represented by these.