JP5115972B2 - Process for producing aromatic amides - Google Patents

Description

The present invention relates to a method for producing an aromatic amide used as a color photographic drug cyan coupler.

As a method for producing an aromatic amide used as a color photographic drug cyan coupler, a method in which o-aminophenols are subjected to a condensation reaction with acid chlorides in the presence of sodium acetate in acetic acid (Patent Document 1), o -Method of reacting hydrochloride of aminophenol with acid chloride in acetone solvent in presence of quinoline (Patent Document 2), o-aminophenol obtained by hydrogenation with Ni-based catalyst and acid chloride A method of performing a condensation reaction (Patent Document 3), a method of performing a condensation reaction of hydrochlorides of o-aminophenols with acid chlorides (Patent Document 4), and the like are known.

However, these methods require a step of once separating o-aminophenol as a hydrochloride or sulfate, or a step of separating an aromatic amide by diluting crystallization with a poor solvent such as water. However, there are problems that the quality of the obtained aromatic amides is not sufficient for use as a color photographic cyan coupler, and that it is not easy to recover and reuse the solvent.

JP-A-62-73258 U.S. Pat. No. 2,801,171 Japanese Patent No. 3460264 Japanese Patent No. 3765837

An object of the present invention is to provide a method for industrially easily producing high-quality aromatic amides sufficient for use as industrial chemicals, particularly cyan couplers used in color photographic light-sensitive materials.

（式中、Ｒ_１は低級アルキル基を表す。）
で示されるｏ−ニトロフェノール類を炭素数１０以下の芳香族系不活性溶媒中、白金系触媒の存在下に接触還元し、式（２）

（式中、Ｒ_１は低級アルキル基を表す。）
で示されるｏ−アミノフェノール類を得、これを単離することなく式（３）

（式中、Ｒ_２〜Ｒ_４ は水素原子もしくは低級アルキル基を表す）
で示される硫黄分含量が０．５％以下（酸クロリド重量基準）の酸クロリド類と、
酸素濃度が１％以下の不活性ガス雰囲気下で縮合反応させて、式（４）

（式中、Ｒ₁ 〜Ｒ₄ は前記と同じ意味を表わす）
で示される芳香族アミド類を得る製造法であって、アミド化縮合反応後、芳香族系不活性溶媒を減圧下で濃縮し、式（４）で示される芳香族アミド類を晶析する工程を含むことを特徴とする式（４）で示される芳香族アミド類の製造法に関する。 As a result of studying a method for industrially obtaining a high-quality photographic drug coupler, the present inventors have found that the present inventors have not isolated o-aminophenols as hydrochlorides or sulfates. By amidating and condensing in an inert gas atmosphere such as nitrogen, concentrating the aromatic inert solvent under reduced pressure, and crystallizing the aromatic amide, the yield is simple, and the industrial The present invention was completed by finding that a high-quality aromatic amide compound can be obtained by a particularly advantageous method with excellent productivity.
That is, the present invention provides the formula (1)

(In the formula, R ₁ represents a lower alkyl group.)
The o-nitrophenol represented by the formula (2) is catalytically reduced in an aromatic inert solvent having 10 or less carbon atoms in the presence of a platinum catalyst.

(In the formula, R ₁ represents a lower alkyl group.)
The o-aminophenol represented by the formula (3) is obtained without isolation.

(Wherein R _{2 to} R ₄ represent a hydrogen atom or a lower alkyl group)
Acid chlorides having a sulfur content of 0.5% or less (based on the weight of acid chloride),
A condensation reaction is performed in an inert gas atmosphere with an oxygen concentration of 1% or less to obtain a compound of formula (4)

(Wherein R _{1 to} R ₄ represent the same meaning as described above)
A process for obtaining an aromatic amide represented by the formula (4) by concentrating an aromatic inert solvent under reduced pressure after an amidation condensation reaction: It is related with the manufacturing method of aromatic amides shown by Formula (4) characterized by including this.

According to the production method of the present invention, a sufficiently high-quality aromatic amide can be industrially advantageously produced for use as an industrial chemical, particularly as a cyan coupler used in a color photographic light-sensitive material.

The o-nitrophenol represented by the formula (1) used in the present invention will be described.
Examples of R ¹ which is a substituent of the o-nitrophenol of the formula (1) include lower alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and the like. Specific examples of the compound include 2-nitro-4,6-dichloro-5-methylphenol, 2-nitro-4,6-dichloro-5-ethylphenol, 2-nitro-4,6-dichloro-5-n. -Propylphenol, 2-nitro-4,6-dichloro-5-isopropylphenol, 2-nitro-4,6-dichloro-5-n-butylphenol, 2-nitro-4,6-dichloro An example is -5-sec-butylphenol.

The o-aminophenol of the formula (2) used in the present invention will be described.
As R < ₁ > which is a substituent of o-aminophenol of Formula (2), lower alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, are mentioned, for example.
Specific examples of the compound include 2-amino-4,6-dichloro-5-methylphenol, 2-amino-4,6-dichloro-5-ethylphenol, 2-amino-4,6-dichloro-5-n- Propylphenol, 2-amino-4,6-dichloro-5-isopropylphenol, 2-amino-4,6-dichloro-5-n-butylphenol, 2-amino-4,6-dichloro-5-sec-butylphenol Illustrated.
These compounds are obtained by catalytic reduction of o-nitrophenols represented by the formula (1) in an aromatic inert solvent having 10 or less carbon atoms in the presence of a platinum catalyst.

Next, the acid chlorides of the formula (3) having a sulfur content of 0.5% or less will be described.
As the substituents R ² , R ³ and R ⁴ of the acid chlorides of the formula (3), methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s- Butyl group, t-butyl group, n-pentyl group, i-pentyl group, s-pentyl group, t-pentyl group, neo-pentyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, t- Examples thereof include a lower alkyl group such as a hexyl group or a hydrogen atom. In the amidation condensation reaction of the present invention, when the sulfur content (amount based on the weight of acid chloride) increases, the performance as a photographic coupler decreases. Acid chlorides of the formula (3) having a sulfur content of 0.5% or less, more preferably 0.3% or less are used in the amidation condensation reaction.

Specific acid chlorides include 2-ethylphenoxyacetic acid chloride, 4-ethylphenoxyacetic acid chloride, α- (2-isopropylphenoxy) butyric acid chloride, α- (3,5-diisopropylphenoxy) butyric acid chloride, α- ( 2-t-amyl-4-methylphenoxy) butyric acid chloride, α- (2,4-di-t-amylphenoxy) butyric acid chloride, α- (2,4-di-t-amylphenoxy) valeric acid chloride, etc. α-substituted aliphatic carboxylic acid chlorides are exemplified.

Such acid chlorides of the formula (3) are, for example, a method of reacting phosgene or oxalyl chloride not containing sulfur with a carboxylic acid, or a method of reacting phosphorus oxychloride with a carboxylic acid (Japanese Patent Laid-Open No. 2003-26630). But you can get it.
Further, in order to reduce the sulfur content of the acid chlorides obtained by reacting carboxylic acid with thionyl chloride to the above level, the sulfur content is 0.5% or less, more preferably 0.3% or less. You may use what you did.

Next, the step of subjecting the acid chloride of formula (3) to the amidation condensation reaction with the o-aminophenol of formula (2) will be described below.
The usage-amount of acid chloride is 0.95-1.05 mol times normally with respect to o-aminophenol of Formula (2), More preferably, it is 0.99-1.00 mol times.

The amidation condensation reaction is carried out in an aromatic inert solvent having 10 or less carbon atoms used in the catalytic hydrogenation of formula (1). Examples of the inert solvent include toluene, xylene, benzene, ethylbenzene, chlorobenzene, and the like. Preferably, toluene and xylene are used alone or in combination. The amount used is usually 5 to 20 times by weight, preferably 6 to 10 times by weight with respect to o-aminophenols.

The reaction temperature is usually 30-40 ° C.
The reaction is usually carried out by dropping acid chloride into o-aminophenols and an aromatic inert solvent, or charging all reagents at 10 ° C. or lower and heating to raise the temperature.
In amidation condensation, oxygen in the atmosphere oxidizes o-aminophenol and affects the reaction. Therefore, in order to obtain high-purity aromatic amides with higher yield, nitrogen or the like with an oxygen concentration of 1% or less In an inert gas atmosphere.

Since hydrogen chloride is generated in this reaction, it is preferable to use a deoxidizing agent. The reaction can be performed more easily by using a deoxidizer.
Examples of the deoxidizer that can be used include inorganic bases such as alkali metal carbonates such as sodium carbonate and potassium carbonate, and alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate.
The amount used is usually up to about 0.75 mol times with respect to o-aminophenol when a diacid base is used, and is up to about 1.5 mol times with a monoacid base. .

In this invention, the process of concentrating an inert solvent from the reaction liquid after amidation condensation reaction under reduced pressure, and crystallizing the aromatic amides shown by Formula (4) is included. This step may be performed at any stage. Usually, it is carried out in the first step after the reaction, but it is more preferred to carry out the reaction in a reaction solution that has been washed with water and separated by liquid separation from the viewpoint of removing water-soluble impurities. After carrying out the process of the present invention, it can be subjected to a filtration process to take out a high-quality aromatic amide as a target product with a high yield. Since the wet cake of aromatic amides taken out in the filtration step is substantially free of moisture, the inert solvent can be recovered in the drying step without complicated operations. Easy to use.

In the present invention, the temperature at which the inert solvent is concentrated under reduced pressure is preferably 30 to 60 ° C. When the concentration temperature is less than 30 ° C., it takes a long time for concentration, which is not preferable. When the temperature exceeds 60 ° C., the resulting aromatic amide tends to be colored and tends to be unfavorable.

The crystallization temperature is preferably 0 to 60 ° C, and the crystal filtration temperature is preferably 0 to 25 ° C. When the filtration temperature is less than 0 ° C., impurities are not sufficiently removed, and high-quality aromatic amides tend not to be obtained. When the filtration temperature exceeds 25 ° C., aromatic amides are eluted in the filtrate, so the yield tends to decrease. The filtered crystal is obtained as an aromatic amide compound from which residual solvent and moisture have been removed by washing and drying as necessary.

The amount of the inert solvent after concentration is preferably 1.0 to 2.5 times that of the aromatic amide. When the amount of the solvent is less than 1.0 times, the fluidity of the crystallization solution is lowered, the removal of impurities in the filtration step is insufficient, the coloring component tends to remain, and high-purity aromatic amides cannot be obtained. .
When the amount of the solvent exceeds 2.5 times, the amount of aromatic amide eluted in the filtrate tends to increase and the yield tends to decrease.

Examples of the aromatic amides of the formula (4) obtained by this method include 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxy Phenyl) butanamide, 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-methyl-2-hydroxyphenyl) butanamide, 2- (2,4-di-t- Pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) acetamide, 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4 -Methyl-2-hydroxyphenyl) acetamide, 2- (2-t-pentyl 4-methylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide, 2- (2- t-pe Til 4-methylphenoxy) -N- (3,5-dichloro-4-methyl-2-hydroxyphenyl) butanamide, 2- (2-t-pentyl 4-methylphenoxy) -N- (3,5-dichloro- 4-ethyl-2-hydroxyphenyl) acetamide, 2- (2-t-pentyl 4-methylphenoxy) -N- (3,5-dichloro-4-methyl-2-hydroxyphenyl) acetamide, 2- ( 2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) valeric amide, 2- (2,4-di-t-pentylphenoxy) -N -(3,5-dichloro-4-methyl-2-hydroxyphenyl) valeric acid amide and the like are exemplified.

As described above, the aromatic amides of the formula (4) can be obtained from the carboxylic acid chlorides and aminophenol by the method of the present invention by a simple method with high yield, the quality is good in hue, and the HPLC purity is 99.5% or more. The aromatic amides become cyan couplers that form excellent images.

(Example)
EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to this.
In the present invention, the content of the compound represented by the formula (1) is determined based on the compound represented by (1) when the sample is separated by high performance liquid chromatography (HPLC) under the following conditions and measured at a detection wavelength of 230 nm. Expressed by area percentage.
Column: Capcellpack C18 (5 μm, 4.0 mmφ × 250 mm)
Mobile phase: Liquid A: acetonitrile (90%), liquid B: water (10%)
Flow rate: 1.0 ml / min, column temperature: 40 ° C., detection wavelength: UV 230 nm

(Reference Example 1)
Charge 320.5 g (1.0 mol) of 2- (2,4-di-t-pentylphenoxy) butyric acid and 100 g of xylene into a 1 L flask, and charge 24.1 g (0.33 mol) of N, N-dimethylformaldehyde. . Under a nitrogen atmosphere, the temperature was kept at 35 ° C., 107.3 g (0.70 mol) of phosphorus oxychloride was added dropwise over 2 hours, and the reaction was further completed by stirring at 50 ° C. for 12 hours. The xylene layer and the by-product layer were easily separated by allowing to stand at the same temperature for 0.5 hour. Subsequently, the by-product separated into the lower layer was separated and removed to obtain 430 g of a xylene solution of 2- (2,4-di-tert-pentylphenoxy) butyric acid chloride. As a result of analyzing the content, the concentration of 2- (2,4-di-tert-pentylphenoxy) butyric chloride was 78.0%, and the sulfur content was 1 ppm or less (below the detection limit).

(Reference Example 2)
Charge 320.5 g (1.0 mol) of 2- (2,4-di-t-pentylphenoxy) butyric acid and 100 g of toluene to a 1 L flask, and charge 24.1 g (0.33 mol) of N, N-dimethylformaldehyde. . Under a nitrogen atmosphere, the temperature was kept at 35 ° C., 107.3 g (0.70 mol) of phosphorus oxychloride was added dropwise over 2 hours, and the reaction was further completed by stirring at 50 ° C. for 12 hours. The toluene layer and the by-product layer were easily separated by allowing to stand at the same temperature for 0.5 hour. Subsequently, the by-product separated into the lower layer was separated and removed to obtain 430 g of a toluene solution of 2- (2,4-di-tert-pentylphenoxy) butyric acid chloride. As a result of analyzing the content, the concentration of 2- (2,4-di-tert-pentylphenoxy) butyric chloride was 78.0%, and the sulfur content was 1 ppm or less (below the detection limit).

Preparation of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide 2-nitro-4,6-dichloro-5-ethylphenol 23.6 g (0.1 mol) and 100 g of xylene are charged into a 500 ml autoclave, and 0.15 g of 3% platinum carbon catalyst is charged. After nitrogen substitution, catalytic hydrogenation is performed at 40 ° C. or less with hydrogen gas. When the hydrogen absorption disappeared and the reduction was completed, the catalyst was filtered to obtain 144 g of a xylene solution of 2-amino-4,6-dichloro-5-ethylphenol. The yield of 2-amino-4,6-dichloro-5-ethylphenol was 100%.
To 124 g of the xylene solution of 2-amino-4,6-dichloro-5-ethylphenol obtained, xylene solution 43 of 2- (2,4-di-tert-pentylphenoxy) butyric acid chloride obtained in Reference Example 1 was added. 0.4 g (0.1 mol) and 7% sodium bicarbonate aqueous solution 174 g were dropped and stirred at a temperature of 30 to 50 ° C. and reacted for 4 hours. After the reaction, the mixture was allowed to stand at 45 to 50 ° C. for 0.5 hour, so that it was easily separated into a xylene layer and an aqueous layer. Next, the lower aqueous layer was removed, 100 g of water was charged at the same temperature, washed with water and separated.
161 g of a xylene layer containing 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide was heated at a temperature of 30 to 30 under a reduced pressure of 2.0 kPa. After concentrating to 75 g at 60 ° C, it was cooled and crystallized to 5 ° C. After crystallization, the mixture was filtered at 5 ° C., and the crystals were washed with 40 g of xylene to obtain white crystals. The yield of the amidation step of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide after drying was 94.1%. It was.
The quality was mp145-146 ° C., purity 99.8%, 10 w / v% ethyl acetate solution 456 nm absorbance (1 cm cell) 0.01 and good.

Preparation of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide 2-nitro-4,6-dichloro-5-ethylphenol 23.6 g (0.1 mol) and 100 g of toluene are charged into a 500 ml autoclave, and 0.15 g of 3% platinum carbon catalyst is charged. After nitrogen substitution, catalytic hydrogenation is performed at 40 ° C. or less with hydrogen gas. When the hydrogen absorption disappeared and the reduction was completed, the catalyst was filtered to obtain 144 g of a toluene solution of 2-amino-4,6-dichloro-5-ethylphenol. The yield of 2-amino-4,6-dichloro-5-ethylphenol was 100%.
The toluene solution 43 of 2- (2,4-di-tert-pentylphenoxy) butyric acid chloride obtained in Reference Example 2 was added to 124 g of the toluene solution of 2-amino-4,6-dichloro-5-ethylphenol obtained. .4 g (0.1 mol) and 174 g of 7% sodium bicarbonate water at a temperature of 30 to 50 ° C.
And stirred for 4 hours. After the reaction, the mixture was allowed to stand at 45 to 50 ° C. for 0.5 hour, so that it was easily separated into a toluene layer and an aqueous layer. Next, the lower aqueous layer was removed, 100 g of water was charged at the same temperature, washed with water and separated.
161 g of toluene layer containing 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide was heated under a reduced pressure of 6.0 kPa at a temperature of 30 to After concentrating to 65 g at 60 ° C., it was cooled and crystallized to 20 ° C. After crystallization, the mixture was filtered at 20 ° C., and the crystals were washed with 40 g of toluene to obtain white crystals. The amidation step yield of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide after drying was 93.9%. It was.
The quality was mp145-146 ° C., purity 99.9%, 10 w / v% ethyl acetate solution 456 nm absorbance (1 cm cell) 0.01 and good.

(Comparative Example 1)
Preparation of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide 2-nitro-4,6-dichloro-5-ethylphenol 23.6 g (0.1 mol) and 100 g of toluene are charged into a 500 ml autoclave, and 0.15 g of 3% platinum carbon catalyst is charged. After nitrogen substitution, catalytic hydrogenation is performed at 40 ° C. or less with hydrogen gas. When the hydrogen absorption disappeared and the reduction was completed, the catalyst was filtered to obtain 144 g of a toluene solution of 2-amino-4,6-dichloro-5-ethylphenol. The yield of 2-amino-4,6-dichloro-5-ethylphenol was 100%.
The toluene solution 43 of 2- (2,4-di-tert-pentylphenoxy) butyric acid chloride obtained in Reference Example 2 was added to 124 g of the toluene solution of 2-amino-4,6-dichloro-5-ethylphenol obtained. .4 g (0.1 mol) and 174 g of 7% sodium bicarbonate water at a temperature of 30 to 50 ° C.
And stirred for 4 hours. After the reaction, the mixture was allowed to stand at 45 to 50 ° C. for 0.5 hour, so that it was easily separated into a toluene layer and an aqueous layer. Next, the lower aqueous layer was removed, 100 g of water was charged at the same temperature, washed with water and separated.
A toluene layer (161 g) containing 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide was heated under a reduced pressure of 23.0 kPa at a temperature of 65-65. After concentrating to 75 g at 80 ° C., it was cooled and crystallized to 5 ° C. After crystallization, the mixture was filtered at 5 ° C., and the crystals were washed with 40 g of toluene to obtain white crystals. The amidation step yield of 2- (2,4-di-t-pentylphenoxy) -N- (3,5-dichloro-4-ethyl-2-hydroxyphenyl) butanamide after drying was 94.0%. It was.
The quality was poor, mp 145-146 ° C., purity 99.7%, 10 w / v% ethyl acetate solution 456 nm absorbance (1 cm cell) 0.10.

Claims (3)

Formula (1)

(In the formula, R ₁ represents a lower alkyl group.)
The o-nitrophenol represented by the formula (2) is catalytically reduced in an aromatic inert solvent having 10 or less carbon atoms in the presence of a platinum catalyst.

(In the formula, R ₁ represents a lower alkyl group.)
The o-aminophenol represented by the formula (3) is obtained without isolation.

(Wherein R _{2 to} R ₄ represent a hydrogen atom or a lower alkyl group)
Acid chlorides having a sulfur content of 0.5% or less (based on the weight of acid chloride),
A condensation reaction is performed in an inert gas atmosphere with an oxygen concentration of 1% or less to obtain a compound of formula (4)

(Wherein R _{1 to} R ₄ represent the same meaning as described above)
The aromatic amides represented by formula (4) are obtained by concentrating the aromatic inert solvent under reduced pressure at 60 ° C. or lower after the amidation condensation reaction, A process for producing an aromatic amide represented by the formula (4), which comprises a step of crystallizing. The production method according to claim 1, wherein the concentration under reduced pressure is 30 to 60 ° C, the crystallization temperature is 0 to 60 ° C, and the crystal filtration temperature is 0 to 25 ° C. The method according to claim 1 or 2, wherein the amount of the aromatic inert solvent after concentration under reduced pressure is in the range of 1.0 to 2.5 times the amount of the aromatic amide.