JP3820557B2 - Process for producing 5-amino-2-nitrophenol - Google Patents

Description

[0001]
[Industrial application fields]
The present invention relates to a novel process for producing 5-amino-2-nitrophenol useful as a synthetic intermediate for couplers for color photographic light-sensitive materials, pharmaceuticals, agricultural chemicals and the like.
[0002]
[Prior art]
There are few examples of the synthesis method of 5-amino-2-nitrophenol, and there is always a problem that impurities are by-produced.
[0003]
For example, a method described in DRP285638 is known as a method for synthesizing 5-amino-2-nitrophenol. In this patent, 3-acetamidobenzenesulfonic acid is nitrated in sulfuric acid to give 5-acetamido-2-nitrobenzenesulfonic acid, which is heated for 1 hour at 135 ° C. in the presence of sodium hydroxide in methanol to obtain the desired product. Yes. However, in this method, the yield is low and most of the product is 5-amino-2-nitroanisole. When 5-amino-2-nitrophenol is to be obtained, the ether cleavage step is performed next. Is required.
[0004]
In J. Chem. Soc., 1930, 1910 to 1916 (1930), 4-nitro-N, N′-diacetyl-m-phenylenediamine is hydrolyzed in an aqueous potassium hydroxide solution. However, in this method, 3-amino-4-nitrophenol is the main product, and the production ratio with 5-amino-2-nitrophenol is approximately 7: 3.
[0005]
Further, in the method using 3-acetamidophenol as a raw material, which is known from J. Am. Chem. Soc., 86, 4947 to 4948 (1964) and JP-A-63-22552, the selectivity of nitro group substitution is a problem. It becomes. That is, when 3-acetamidophenol is nitrated at 10 ° C. to 40 ° C., a 2-nitro form and a 4-nitro form are formed at a ratio of about 1: 1. Therefore, even if both isomers are separated and purified by the method of JP-A-63-22552, the yield is naturally low, and further, a hydrolysis step of amide is required thereafter. On the other hand, when the nitration reaction temperature is as low as −10 ° C. to −5 ° C., a large amount of unreacted 3-acetamidophenol generally remains, and separation and purification from the produced target product becomes complicated.
[0006]
[Problems to be solved by the invention]
The present invention has been made in order to solve the above-described problems in the production of conventional 5-amino-2-nitrophenol, and the compound is obtained in high yield, with a small amount of isomers and by-products, and high purity. It aims at providing the manufacturing method for obtaining.
[0007]
[Means for solving problems]
In the present invention, a compound represented by the formula (1) is used as a raw material and is selectively deacylated in an alcohol solvent in the presence of an alkali to obtain a compound represented by the formula (2), and the amino group is diazotized. Then, without removing the diazonium salt, 5-amino 2-nitrophenol [formula (3)] is produced by thermally decomposing and hydroxylating in the presence of sulfuric acid and simultaneously hydrolyzing the amide. .
[0008]
In the method of the present invention, a 4-nitro-1,3-phenylenediamine derivative used as a reaction raw material is represented by the general formula (1). In the formula (1), R represents a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted aryl group. Here, the lower alkyl group is a linear or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as a methyl group, a trifluoromethyl group, an ethyl group, an n-propyl group, or an iso-propyl group. N-butyl group, sec-butyl group and tert-butyl group, and aryl group includes phenyl group, o, m, p-methylphenyl group, o, m, p-ethylphenyl group, o, m , p, -methoxyphenyl group, o, m, p, -ethoxyphenyl group, o, m, p, -fluorophenyl group, o, m, p-chlorophenyl group, o, m, p, -bromophenyl group, o, m, p-hydroxyphenyl group and the like. Among these, a methyl group or an ethyl group gives particularly favorable reaction results when the method of the present invention is used.
[0009]
Examples of the alcohol solvent used for selective deacylation in the present invention include methanol, ethanol, 1-propanol, 2-propanol, n-butanol, sec-butanol, tert-butanol, and the like. Methanol, ethanol, 1-propanol and 2-propanol give particularly good reaction results when the method of the present invention is used. The amount of the alcohol used is usually 1 to 20 parts by weight, preferably 3 to 10 parts by weight, based on 1 part by weight of the starting 4-nitro-1,3-phenylenediamine derivative (1). Is done.
[0010]
Examples of the alkali used in the selective deacylation in the present invention include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methylate, and sodium ethylate. Among these, sodium hydroxide or potassium hydroxide gives particularly good reaction results when the method of the present invention is used. The amount of alkali used varies depending on the reaction substrate, its concentration, and the type of solvent, but is preferably 0.5 to 3.3 with respect to the starting 4-nitro-1,3-phenylenediamine derivative (1). The equivalent is 0 times, more preferably 0.8 to 1.5 times equivalent.
[0011]
In the method of the present invention, the reaction proceeds by stirring and mixing the 4-nitro-1,3-phenylenediamine derivative (1), alcohol and alkali. The temperature during the reaction varies greatly depending on the reaction substrate, its concentration, the type of alcohol and alkali, and the amount used, but is preferably 100 ° C. or less, and particularly preferably in the range of 10 ° C. to 80 ° C. However, the present invention is not limited to this, and the time is not particularly limited.
[0012]
In the method of the present invention, the product after the deacylation reaction is completed by neutralizing the alkali used with an equivalent amount of acid and then treating the product according to a conventional method such as a crystallization method to obtain the desired 5-amide. -2-Nitroaniline (2) is obtained. Examples of the acid used here include hydrochloric acid, sulfuric acid, nitric acid, and acetic acid, but are not limited thereto.
[0013]
Examples of the diazotizing agent used in diazotization of the 5-amido-2-nitroanilines (2) in the present invention include nitrites such as sodium nitrite and potassium nitrite, alkyl nitrites such as methyl nitrite and ethyl nitrite. And nitrosyl hydrogen sulfate, etc., but the amine of the compound represented by the formula (2) is generally weakly basic and hardly diazotized. Therefore, in the method of the present invention, it is preferable to use nitrosyl hydrogen sulfate as the diazotizing agent. Nitrosyl hydrogen sulfate can be obtained by adjusting according to a conventional method. The amount used is preferably in the range of 1.0 to 2.0 equivalents, particularly 1.0 to 1.5 equivalents, relative to the starting 5-amido-2-nitroaniline (2).
[0014]
Examples of the solvent used in the diazotization in the present invention include aqueous solutions such as hydrochloric acid, hydrobromic acid and sulfuric acid, propionic acid, acetic acid, or a mixture of acetic acid and dioxane, acetic acid and THF, acetic acid and acetonitrile. In the method of the invention, diazotization in an anhydrous solvent is preferred, and a mixture of acetic acid and acetic acid and dioxane, acetic acid and THF, acetic acid and acetonitrile, etc. is suitable. The solvent is used in an amount of usually 1 to 40 parts by weight, preferably 3 to 20 parts by weight, based on 1 part by weight of the starting 5-amido-2-nitroaniline (2). .
[0015]
In the method of the present invention, the reaction proceeds by dissolving the 5-amido-2-nitroaniline (2) in an acidic solvent and adding the diazotizing agent with stirring. The temperature during the reaction varies depending on the reaction substrate, its concentration, the type of acidic solvent and the amount used, and the type of diazotizing agent, but is preferably in the range of −10 ° C. to 40 ° C., particularly −5 ° C. to 20 ° C. A range of ° C is preferred. However, the present invention is not limited to this. In addition, the time is preferably as fast as possible within the appropriate temperature range, but this is not particularly limited.
[0016]
In the present invention, the reaction is carried out in a nitrogen atmosphere, but in addition, an inert gas such as argon or helium can be used.
[0017]
The 5-amido-2-nitrobenzenediazonium salt obtained by the present invention can be taken out by a crystallization method, but in general, the diazonium salt is unstable and easily decomposes, so that after the diazotization reaction, It is advantageous to proceed to the next step promptly without removing the diazonium salt.
[0018]
The 5-amido-2-nitrobenzenediazonium salt obtained by the present invention can be led to the target 5-amino-2-nitrophenol (3) by thermal decomposition in water or an acidic solvent. In the reaction, it is advantageous that the hydroxylation as well as the hydrolysis of the amide can be carried out simultaneously in one pot.
[0019]
Examples of the acidic aqueous solution used for the decomposition of the 5-amido-2-nitrobenzenediazonium salt in the present invention include hydrochloric acid, hydrobromic acid, nitric acid and sulfuric acid of any concentration, but hydrochloric acid, hydrobromic acid, nitric acid If an acid is used, the anionic species of these acids may be substituted, so it is preferable to use sulfuric acid. Moreover, when nitrosyl hydrogen sulfate is used as the diazotizing agent, water can be used as it is, not an acidic aqueous solution. The water or acidic aqueous solution used in the reaction is used in a proportion of 3 to 100 parts by weight, preferably 5 to 50 parts by weight, based on 1 part by weight of the starting 5-amido-2-nitrobenzenediazonium salt.
[0020]
In the method of the present invention, the reaction proceeds by adding the reaction solution after completion of the diazotization reaction little by little into heated water or an acidic aqueous solution while stirring. The temperature during the reaction is preferably in the range of 50 ° C. to 180 ° C., but is not limited thereto. Also, the time is not particularly limited.
[0021]
The target product, 5-amino-2-nitrophenol, is extracted with a low water-soluble solvent such as toluene, xylene, or ethyl acetate after the reaction is completed. After removing water-soluble impurities by washing with water, the solvent is distilled off. Can be obtained. The reaction solution is neutralized with an alkali such as sodium acetate, potassium acetate, sodium hydroxide, sodium carbonate, and then water and solvent are distilled off, and the concentrate is extracted with a solvent such as acetone, ethyl acetate, THF, and the like. After the lysate is filtered off, the solvent can be distilled off. If necessary, recrystallization using methanol, ethanol or the like is also possible.
[0022]
【The invention's effect】
According to the present invention, a 4-nitro-1,3-phenylenediamine derivative (1) is selectively deacylated in an advantageous manner and led to 5-amido-2-nitroanilines (2), which are advantageously Can be diazotized to give a 5-amido-2-nitrobenzenediazonium salt, which is further hydrolyzed by an advantageous method to obtain a high yield of the final 5-amino-2-nitrophenol (3). And can be manufactured with high purity.
[0023]
【Example】
EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
[0024]
[Example 1]
100 ml of methanol, 20 g (0.087 mol) of 4-nitro-N, N′-diacetyl-m-phenylenediamine and 4.6 g (0.082 mol) of potassium hydroxide are placed in a 300 ml four-head flask at 20 ° C. to 30 ° C. In the range of 2 hours. Next, 8.8 g (0.082 mol) of 35% aqueous hydrochloric acid and 100 ml of water were added, cooled to 10 ° C., filtered, and 14.1 g of 3-amino-4-nitroacetanilide brown crystals (yield 85.7%). )
[0025]
A 50 ml eggplant type Kolben was charged with 24 ml of concentrated sulfuric acid and stirred and cooled with a magnetic stirrer. 3.9 g (0.057 mol) of sodium nitrite was added little by little at 20 ° C. or less, and then heated and stirred to 70 ° C. to make the solution uniform, and then cooled again. On the other hand, 10 g (0.051 mol) of 3-amino-4-nitroacetanilide, 60 ml of acetic acid and 15 ml of acetonitrile were placed in a 100 ml four-headed flask, heated to 40 ° C. with stirring and uniformly dispersed, and then cooled to 5 ° C. The nitrosyl hydrogen sulfate prepared previously was dripped in the range of 5 degreeC-10 degreeC over 30 minutes in nitrogen atmosphere, and it stirred for 10 minutes after that.
[0026]
In a 300 ml four-headed flask, 40 ml of water and 30 ml of concentrated sulfuric acid were placed and heated with stirring, and kept at 120 ° C. The reaction solution of the previous 5-acetamido-2-nitrobenzenediazonium salt was added dropwise over 30 minutes, and then reacted at the same temperature for 10 minutes. After cooling the internal temperature, sodium acetate was added until PH4 was reached, the solvent was distilled off under reduced pressure, 150 ml of acetone was extracted into the concentrate, and the insoluble material was filtered off, and then acetone was distilled off under reduced pressure to remove 5-amino. As a result, 6.0 g (yield 76.0%) of 2-nitrophenol dark brown crystals was obtained.
[0027]
Total yield 65.1% from 4-nitro-N, N′-diacetyl-m-phenylenediamine.
1H-NMR (DMSO-d6); δ ppm
6.06 [d. 1H (6th)]
6.22 [dd 1H (4th place)]
6.98 [broad. 2H (-NH2)]
7.78 [d. 1H (3rd place)]
11.09 [broad. 1H (-OH)]
[0028]
[Example 2]
In Example 1, the reaction was performed in the same manner as in Example 1 except that 100 ml of ethanol was used instead of 100 ml of methanol. 13.5 g (yield 82.1%) of 3-amino-4-nitroacetanilide was obtained, and 10 g of this was used and reacted in the same manner as in Example 1 to obtain 5.8 g of 5-amino-2-nitrophenol. (Yield 73.5%) was obtained.
[0029]
Total yield 60.3% from 4-nitro-N, N′-diacetyl-m-phenylenediamine.
[0030]
[Example 3]
Put 300 ml of methanol, 25 g (0.069 mol) of 4-nitro-1,3 dibenzanilide and 2.6 g (0.066 mol) of sodium hydroxide in a 300 ml four-head flask and stir for 3 hours in the range of 30 ° C to 35 ° C. I let you. Next, 6.6 g (0.066 mol) of 35% aqueous hydrochloric acid and 130 ml of water were added, cooled to 10 ° C., filtered, and 11.1 g (yield 61.2) of 3-amino-4-nitrobenzanilide tan crystals. %).
[0031]
A 50 ml eggplant type Kolben was charged with 18 ml of concentrated sulfuric acid and stirred and cooled with a magnetic stirrer. 2.9 g (0.042 mol) of sodium nitrite was added little by little at 20 ° C. or less, and then heated and stirred to 70 ° C. to make the solution uniform and then cooled again. On the other hand, 10 g (0.038 mol) of 3-amino-4-nitrobenzanilide, 60 ml of acetic acid and 15 ml of acetonitrile were placed in a 100 ml four-head flask, heated to 40 ° C. with stirring and uniformly dispersed, and then cooled to 5 ° C. The nitrosyl hydrogen sulfate prepared previously was dripped in the range of 5 degreeC-15 degreeC over 30 minutes in nitrogen atmosphere, and it stirred for 10 minutes after that.
[0032]
In a 300 ml four-headed flask, 40 ml of water and 30 ml of concentrated sulfuric acid were added and heated with stirring to be kept at 120 ° C. The reaction solution of the previous 5-benzamido-2-nitrobenzenediazonium salt was added dropwise over 30 minutes, and then reacted at the same temperature for 10 minutes. After cooling the internal temperature, sodium acetate was added until PH4 was reached, the solvent was distilled off under reduced pressure, 150 ml of acetone was extracted into the concentrate, the insoluble material was filtered off, acetone was distilled off under reduced pressure, and 30 ml of ethanol was added. Recrystallization gave 3.3 g of 5-amino-2-nitrophenol (yield 56.3%).
[0033]
Total yield 34.5% from 4-nitro-1,3-dibenzanilide.

Claims (6)

A 4-nitro-1,3-phenylenediamine derivative represented by the formula (1) [wherein R represents a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted aryl group] is an alcohol solvent. In the presence of an alkali, the compound was selectively deacylated to give 5-amido-2-nitroanilines represented by the formula (2) [wherein R is the same as R in the formula (1)]. Then, the amino group is diazotized and thermally decomposed to introduce a hydroxyl group, thereby producing a 5-amino-2-nitrophenol [formula (3)].

The method for producing 5-amino-2-nitrophenol [formula (3)] according to claim 1, wherein R is a methyl group or an ethyl group in formula (1) and formula (2). The method for producing 5-amino-2-nitrophenol [formula (3)] according to claim 1, wherein the alcohol solvent is selected from the group consisting of methanol, ethanol, 1-propanol, and 2-propanol. The method for producing 5-amino-2-nitrophenol [formula (3)] according to claim 1, wherein the alkali is sodium hydroxide or potassium hydroxide. The method for producing 5-amino-2-nitrophenol [formula (3)] according to claim 1, wherein the diazotizing agent is nitrosyl hydrogen sulfate. A process for producing 5-amino-2-nitrophenol [formula (3)], wherein the hydrolysis is carried out in the presence of sulfuric acid without introducing a diazonium salt, the hydroxyl group is introduced, and the hydrolysis of the amide is simultaneously performed. .