JPH03176458A - Production of acetic acid p-aminophenyl - Google Patents

Abstract

PURPOSE:To advantageously obtain the title compound useful in the fields of organic synthetic chemicals such as agricultural chemical, medicine, dye, etc., without using expensive reducing agent, etc., in short synthetic steps by subjecting p-nitrophenyl acetate used as a raw material to catalytic reduction under specific conditions. CONSTITUTION:p-Nitrophenyl acetate used as a raw material is subjected to a catalytic reduction in the presence of a reduction catalyst under temperature condition of <=50 deg.C and >=0 deg.C preferably >=10 deg.C to provide the objective compound. A metal catalyst of the group VIII is periodic table, especially palladium or platinum noble metal catalyst is preferably used as the above-mentioned reduction catalyst. The catalyst is used at an amount of 0.1-20wt.% based on the amount of raw material. Furthermore, when a heterogeneous catalyst is used as the reduction catalyst, after reaction, the reaction system is replaced by an inert gas and then the catalyst is separated by filtration, and the motor liquid is concentrated and the solvent is distilled away to provide the objective compound. When a homogeneous catalyst is used, the reaction system is replaced with an inert gas and the solvent is distilled away under reduced pressure, etc., and the residue is purified by distillation to provide the objective compound.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel method for producing ρ-agonophenyl acetate, which has high utility value in the field of organic synthetic chemistry for agricultural medicines, dyes, etc.

More specifically, the present invention provides a method for producing p-aminophenyl acetate by catalytic reduction using p-nitrophenyl acetate as a raw material.

[Problems to be solved by conventional technology and invention] Acetic acid p
-Aminophenyl is known to be a compound with high utility value as an intermediate in the production of liquid crystal compounds. (US Pat. No. 3,769.327) It is also a compound that can be used as an intermediate in the production of acedoanofen, which is currently widely used as a cold medicine around the world. However, there are few examples of conventional methods for producing ρ-aminophenyl acetate, and only the methods shown below are known.

That is, p-agonophenol or acetic acid p-
-Nitrophenyl, and the method using p-aminophenol as a raw material is to react p-aminophenol with benzaldehyde to form N-benzylidene-p~lyaminophenol, and then react with acetic anhydride in alkaline water. -Benzylidene-〇-acetyl-p-aminophenol is obtained and further treated with sulfuric acid to obtain vinegar fIip-aminophenyl (Galatis).

Ber, + 51.849 (1926)]. Although this method has a relatively good yield, it must be said that the process is long and complicated.

In addition, as a production method by reduction from p-nitrophenyl acetate, (+):/zene/aqueous teno iron powder reduction method. (S, E, H
az-1eL+J, 8-, Ches, Soc,, 66
, 1781 (1944)) (2) A method using sodium borohydride/stannic chloride as a reducing agent in a mixed solvent of ethyl acetate and isobutanol. (T, 5atoh
et a1, Chew.

Pharm, [1u11. , d, 1443 (19
81)) (3) Method by electrolytic reduction in dilute sulfuric acid. (Com
pL, Rend, +zaj3.3046 (1964)
), but method (1) has an extremely low yield of less than 10%, and method (2), although high in terms of yield, requires the use of an expensive reducing agent. Furthermore, since a large excess of stannic chloride is used, post-treatment after the reaction is complicated, and therefore it cannot be considered an industrial production method. Even with the electrolytic reduction method (3), the equipment costs are high and it is difficult to call it a practical method.

As described above, the current state of the art is that the known production methods are not industrially satisfactory in terms of reaction steps, yield, auxiliary raw materials, equipment costs, etc.

[Problem to be solved by the invention]

The first object of the present invention is to provide an industrial method for producing p-aminophenyl acetate. The second issue is acetic acid ρ.
-Acetic acid p- by catalytic reduction using nitrophenyl as raw material
An object of the present invention is to provide a method for producing aminophenil.

[Means to solve the problem]

As is clear from its structure, p-nitrophenyl acetate, which is the raw material of the present invention, is a type of active ester, and therefore it itself reacts with amino compounds to produce p-nitrophenol and acetic acid amides. The trend is well known.

For example, based on the studies of the present inventors, equimolar amounts of p-nitrophenyl acetate and aniline are dissolved in Hensen,
When its reactivity was investigated, it was found that 20-30% acetanilide was produced under conditions of 60-70°C for 12 hours. This means that p-nitrophenyl acetate can be converted to p-nitrophenyl acetate.
When converting to -aminophenyl, when a reduction reaction is carried out under neutral conditions, the generated p-aminophenyl acetate reacts with the raw material vinegar fItp-nitrophenyl, resulting in the formation of the target p-aminophenyl acetate and other substances. This suggests that by-products such as N,O-diacetyl-p-a-nophenol and ρ-aξ-nophenol are produced.

This is considered to be the reason why the yield in the iron powder reduction method is extremely low among the prior art techniques.

By the way, a catalytic reduction method is a method commonly used as a method for reducing a nitro group. Particularly recently, catalytic reduction methods using precious metal catalysts such as palladium and platinum have become widely used due to the reduction of industrial waste and the simplicity of the process. Until now, no catalytic reduction method using a noble metal catalyst has been known.

The present inventors have intensively studied the catalytic reduction method of p-nitrophenyl acetate as an industrial method for producing p-nitrophenyl acetate. Under temperature conditions, N
, 0-diacetyl-ρ-7minophenol and p-
It has been found that the yield of the target ρ-aminophenyl acetate decreases due to the by-product of 71 nophenol, and that isolation of the target product from the reaction mixture becomes complicated.

Furthermore, as a result of examining various reaction conditions, the reaction temperature was 50°C.
Under the following conditions, the reaction between p-nitrophenyl acetate and ρ-anophenyl acetate produced by reduction can be suppressed as much as possible, and it can also be selectively suppressed without inducing side reactions such as reduction of the ester moiety. It was found that p-aminophenyl acetate was produced.

The present invention has been made based on this knowledge.

That is, the present invention is a method for producing p-anophenyl acetate, which is characterized by catalytically reducing p-nitrophenyl acetate in the presence of a reduction catalyst at a temperature of 50° C. or less.

In the present invention, p-nitrophenyl acetate is used as a raw material. This compound is easily produced from p-nitrophenol and acetic anhydride.

In the present invention, the catalytic reduction reaction of p-nitrophenyl acetate is usually carried out in an organic solvent. The organic solvent used is not particularly limited as long as it is inert to the raw materials and products and also inert to the reduction reaction.

Specifically, alcoholic solvents such as methanol, ethanol, n-propertool, isopropertool, 5ee-butanol, n-butanol, isobutanol, tert-butanol, methyl cellosolve or cellosolve, hexane, heptane, octane, cyclohexane,
Aliphatic or aromatic hydrocarbon solvents such as benzene, toluene, xylene or ethyl hesozene, carbon tetrachloride,
Aliphatic or aromatic halogenated hydrocarbon solvents such as dichloroethane, trichloroethane, tetrachloroethane, chlorobenzene, dichlorobenzene or trichlorobenzene, ethereal solvents such as diisopropyl ether, tetrahydrofuran, dioxane or ethylene glycol diethyl ether, acetic acid or propionic acid, etc. carboxylic acid solvents, ester solvents such as ethyl acetate or butyl acetate, glycol solvents such as ethylene glycol or triethylene glycol, or N
, N-dimethylformamide, N, N-diethylformamide, N.

N-dimethylacetamide, N,N-diethylacetamide, N-methylpyrrolidone, N,N"-dimethylimidazolidinone, N,N'-dimethylpropylene urea,
Mention may be made of pyridine, picoline, dimethyl sulfoxide, sulfolane or tributyl phosphate.

Of course, the solvents listed here are just examples, and it is clear that the solvents that can be used in the present invention are not limited to these.

Among these solvents, alcohol solvents and hydrocarbon solvents are particularly suitable for the present invention.

The above organic solvents are usually used alone, but it is also possible to use two or more types of solvents in combination.

Moreover, water can coexist within the range that does not impair the purpose of the present invention.

There is no particular restriction on the amount of the organic solvent used, but from the viewpoint of reaction operation and volumetric efficiency, it is usually used in an amount of 0.5 to 20 times the weight of the raw material ρ-nitrophenyl acetate.

The catalytic reduction reaction of p-nitrophenyl acetate in the present invention is carried out in the presence of a reduction catalyst. As the reduction catalyst, various catalysts used in ordinary catalytic reduction reactions can be used, but in particular catalysts from group 8 of the periodic table, that is, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium or platinum. metal catalysts are used.

More preferably, noble metal catalysts such as palladium or platinum are often used.

As the form of the reduction catalyst, either a homogeneous catalyst that dissolves in an organic solvent or a heterogeneous catalyst that does not substantially dissolve in the organic solvent and forms a suspended state can be used. Specifically, homogeneous catalysts such as palladium chloride, palladium acetate, platinum chloride, platinum acetate, or complexes of these with pyridine, triphe, and ruphosphine, colloidal palladium, platinum oxide, or palladium or platinum combined with activated carbon or sulfuric acid are used. Examples include heterogeneous catalysts supported on various inorganic carriers such as barium, aluminum, or silica.

When a metal is supported on a carrier, there is no particular restriction on the content of the metal, but usually a catalyst in which the metal is supported in an amount of 1 to 10% by weight is exclusively used.

Further, although a single catalyst is usually used, it is also possible to use two or more types of catalysts in combination.

If the amount of metal catalyst used is too small, the progress of the reduction reaction will be extremely slow, which is impractical, and if it is used in excess, it is economically undesirable. For this purpose, it is usually 0.1 to 20% relative to the raw material ρ-nitrophenyl acetate.
It is preferably used in an amount of 0.2 to 10% by weight.

In the catalytic reduction reaction of p-nitrophenyl acetate of the present invention, the secondary reaction between the p-aminophenyl acetate produced in the reduction reaction and the raw material is suppressed by setting the reaction temperature to 50°C or less. , as a result, acetic acid ρ-
It can be converted to acinophenyl. When the reaction temperature is higher than 50°C, p-aminophenol and N,0-diacetyl-p-aminophenol are likely to be produced as by-products, and therefore,
The yield of the desired ρ-aminophenyl acetate is significantly reduced. Regarding the lower limit of reaction temperature, from the viewpoint of reaction rate, O'
The temperature is preferably 10°C or higher, more preferably 10°C or higher.

A concrete implementation of the present invention will be described below.

First, the raw material p-nitrophenyl acetate is dissolved or suspended in a predetermined organic solvent. Next, the reaction system is replaced with an inert gas such as nitrogen, and a predetermined amount of noble metal catalyst is charged.Next, the reaction system is sufficiently replaced with an inert gas again, and then hydrogen is introduced to a predetermined amount. The catalytic reduction reaction is carried out at a temperature of . The pressure during the reduction reaction may be normal pressure or increased pressure.

When carrying out the catalytic reduction reaction under pressure, the pressure is preferably 50 atm or less, preferably 30 atm or less in order to suppress side reactions.

Although the reduction reaction time varies depending on the amount of catalyst, reaction temperature, stirring efficiency, etc., it is usually completed within 20 hours.

As described above, in the method of the present invention, p-aminophenyl acetate is produced with a yield of about 90% or more.

The p-anophenyl acetate produced in the catalytic reduction reaction of the present invention can be isolated as follows.

That is, when a heterogeneous catalyst is used as a reduction catalyst,
After the reaction, the reaction system is replaced with an inert gas such as nitrogen, the catalyst is separated by a filtration operation, and the resulting mother liquor is concentrated and the solvent is distilled off to obtain ρ-heaminophenyl acetate. If necessary, it may be purified using purification means such as recrystallization or vacuum distillation.

When a homogeneous catalyst is used as a reduction catalyst, after the reaction, the reaction system is replaced with an inert gas such as nitrogen, the solvent is distilled off by means such as vacuum distillation, and the residue is distilled with an appropriate solvent. It may be purified by means such as thrashing, recrystallization, or ashidome.

〔Example〕

Hereinafter, the present invention will be explained in detail with reference to Examples.

In addition, the analysis by high performance liquid chromatography in the examples was conducted under the following conditions.

<High performance liquid chromatography conditions> Column: Y
MCPack＾-314 (0 ports 5) 6v++φX25c
+++ (Yamamura Kagaku Kenkyushin) Mobile phase: 0.05mo
l KJPO4aQ/methanol = 6/4 (volume ratio)
pll・5.5 Flow rate: 0.4 d/win.

Detector: Ultraviolet spectrophotometer Wavelength = 245 nm Example 1 36.
4 g (0,2 mol) and isopropanol 500-
was loaded. After purging the system with nitrogen, 1.46 g of 5% palladium on carbon (50% by weight product) was charged.

After the inside of the system was sufficiently purged with nitrogen again, it was then purged with hydrogen, and then a reduction reaction was carried out at 20 to 30° C. under normal pressure.

Almost the theoretical amount of hydrogen was absorbed in 3 hours.

After the reaction, the system was purged with nitrogen, and the catalyst was filtered off and washed with a small amount of isopropanol. The filtrate and washing liquid were combined and analyzed using high performance liquid chromatography, and it was found that acetic acid p-
The conversion rate of nitrophenyl was 100%, and the conversion rate of acetic acid p
The production rate of -aminophenyl was 98.8% (to acid #p-nitrophenyl).

The solvent of the filtrate was distilled off under reduced pressure to obtain white crystals of ρ-aminophenyl acetate as a residue. Revenue! 3 (1.4 g, purity 97.0%, yield 97.6% (vs. vinegar #p-nido-a-phenyl).

The obtained crude crystals were purified by recrystallization from petroleum ether to obtain 23.5 g of purified p-aminophenyl acetate having a melting point of 72 to 73°C.

Elemental analysis 4'li (%) HN Actual value 63.38 6.13 9.24C*11. N
Calculated value as o□ 63.54 6.00 9.27
Example 2 18.2 g (0.1 mol) of p-nitrophenyl acetate and 250 d of toluene were added to a 500 d four-way flask.
was loaded. After nitrogen substitution, 5% palladium on carbon 0.4
After the system was sufficiently purged with nitrogen and then with hydrogen, a reduction reaction was carried out at 40 to 50°C under normal pressure. Almost the theoretical amount of hydrogen was absorbed in 3 hours and the reaction was completed.

After the reaction, the reaction mixture was cooled to room temperature, the atmosphere in the system was replaced with nitrogen, and the catalyst was filtered off and washed with a small amount of toluene.

The filter cake liquid was combined and analyzed by high performance liquid chromatography, and the conversion rate of ρ-nitrophenyl acetate was 1OO%, and the production rate of p-aminophenyl acetate was 95.6% (based on p-nitrophenyl acetate). Ta. Further, p-aminophenol and N,O-diacetyl-p-aminophenol as by-products were 1.8% and 1.6%, respectively (based on p-nitrophenyl acetate).

Example 3 p-nitrophenyl acetate 18 in a 300-autoclave
．． 2 g (0.1 mol), 150 iN of ethanol and 0.2 g of 5% palladium/barium sulphate were charged.

After nitrogen replacement followed by hydrogen replacement, 20kg/c+1
The reduction reaction was carried out under pressure at 20-30°C. 4
After the reaction system, which had absorbed approximately the theoretical amount of hydrogen in an hour, was purged with nitrogen, the catalyst was filtered off and washed with a small amount of ethanol. As a result of combining the filtrate and washing liquid and analyzing them using high performance liquid chromatography, the conversion rate of p-nitrophenyl acetate was 10.
0%, the production of p-aminophenyl acetate was 197.6% (vs. p-nitrophenyl acetate), and the by-products of p-aminophenol and N,O~diacetyl p-aminophenol were converted to the raw material p-nitrophenyl acetate. It was less than 1%.

Example 4 A reduction reaction was carried out in the same manner as in Example 1 except that 1.0 g of 5% platinum carbon was used instead of 5% palladium carbon in Example 1. As a result, the production rate of p-aminophenyl acetate was 9
It was 7.6% (based on p-nitrophenyl acetate).

Comparative Example 1 The same procedure as in Example I was carried out except that the temperature of the catalytic reduction reaction in Example 1 was 60 to 70°C. After the reaction, the catalyst was filtered off and the filter cake was analyzed using high performance liquid chromatography, and the production rate of p-aminophenyl acetate was 82.4% (
p-aminophenol and N,O-diacetyl to p-anophenol were produced as by-products in an amount of 8.9% and 8.7%, respectively (versus p-nitrophenyl acetate).

C Effects of the Invention J The method of the present invention, which provides a method for producing p-aminophenyl acetate by catalytic reduction of p-nitrophenyl acetate, is simple in reaction operation, and at the same time has high selectivity and high yield. acetic acid rho
- Not only can aminophenyl be produced, but it is also easy to produce in terms of raw materials, and therefore it is an extremely valuable method from an industrial perspective.

Claims (1)

[Claims] 1. p-nitrophenyl acetate in the presence of a reducing catalyst, 50
1. A method for producing p-aminophenyl acetate, which comprises carrying out catalytic reduction at a temperature of .degree. C. or lower. 2. The method according to claim 1, wherein the reduction catalyst is a metal catalyst of Group 8 of the Periodic Table.