JPS62153262A - Production of halo-substituted aminophenol - Google Patents

Abstract

PURPOSE:To obtain a compound useful as a synthetic intermediate for medicines and agricultural chemicals in good yield, by feeding a solution of a holo- substituted nitrophenol in an alcohol to an aqueous medium containing Raney nickel catalyst, a cyano compound, etc., under pressure of hydrogen to carry out reduction with hydrogen. CONSTITUTION:An aqueous medium containing Raney nickel catalyst, a cyano compound, e.g. dicyandiamide, or a thiazole, e.g. benzothiazole, and an alkali agent, e.g. NaOH, is prepared and a solution of a holo-substituted nitrophenol, e.g. 2,6-dichloro-4-nitrophenol, dissolved in an alcohol, e.g. methanol, is fed to an autoclave and reduced at 60-90 deg.C under 0.5-20kg/cm<2>, preferably 2-10kg/cm pressure of hydrogen to carry out reduction with hydrogen and afford the aimed substance. EFFECT:Inexpensive and readily available Raney nickel is used and formation of by-products by dehalogenation, nuclear hydrogenation, etc., can be suppressed.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a process for producing halo-substituted aminophenols. More specifically, the present invention relates to a method for producing .sub.substituted aminophenols by a hydrogenation method.

BACKGROUND OF THE INVENTION Substituted aminophenols are important intermediates for pharmaceuticals and agricultural chemicals.

Known methods for producing halo-substituted aminophenols include (1) selective ammonolithization of polyhalo-substituted phenols and (2) catalytic reduction of halo-substituted nitrophenols.

For example, for (1), there is a method disclosed in JP-A-57-7451, but the yield is as low as about 80%, which is unsatisfactory.

Regarding ■, 1, for example, Japanese Patent Application Laid-Open No. 59-216855
However, in this method, an expensive platinum catalyst is used to prevent de-I, rogens, and nuclear hydrogenation reactions, but it is necessary to perform rigorous catalyst recovery to avoid cost increases, and its productivity is (Preparation efficiency) is also low and generally not industrially satisfactory.

Problems to be Solved by the Invention Using a catalyst that is industrially easily available (1) By-products from dehalogenation reactions, nuclear hydrogenation reactions, etc. are small.

■ High preparation efficiency.

It is desired to develop a method for producing halogen-substituted aminophenols that satisfies the following requirements.

Means for Solving the Problems The inventors of the present invention have conducted extensive research to solve the above-mentioned problems, and as a result they have arrived at the present invention. That is, the present invention relates to the production of halo-substituted aminophenols, which comprises supplying an alcoholic solution of halo-substituted nitrophenols under hydrogen pressure to an aqueous medium containing a Raney nickel catalyst, a cyanide compound or a thiazole, and an alkali agent, and reducing the hydrogen with hydrogen. provide a method.

In catalytic reductive hydrogenation using Raney nickel, which is industrially available at low cost, the reaction is generally neutral or weakly alkaline due to the nature of the catalyst, but in the hydrogenation of halo-substituted nitrophenols, the nickel itself is acidic. Since it is a substance that exhibits , it is common to react it as an alkali metal salt.

However, since the alkali metal salts of halo-substituted nitrophenols have extremely low solubility in solvents, especially water, it is industrially meaningless to handle them in an aqueous solution.
It will be handled as a slurry, but even with this slurry, depending on the type of 8-day-substituted nitrophenol, at most 15
The upper limit is a concentration of about 20% to 20%, and if the concentration is higher than that, sufficient stirring will not be possible, causing problems in efficiency and reaction during preparation.

The present invention will be described in detail.

Specific examples of halo-substituted nitrophenol as used in the present invention include 2-chloro-4-nitrophenol, 4-chloro-2-nitrophenol, 2-bromo-4-nitrophenol, 4-bromo -2-ditrophenol, 2.6-
Siprolu 4-nitrophenol, 2,6-difuromu 4-nitrophenol, 4-/lolu 6-nitrometacreso-#.

2-chloro-4-nitro-6-medoxymetherphenol, 2-chloro-4-nitro-6-nitrophenol,
Examples include, but are not limited to, 2-chloro-4-nitro-6-methylphenol.

Specific examples of alcohols used to prepare the halo-substituted nitrophenol M nofluco-/l'solt include methanol, ethanol, propyl alcohol, inglobil alcohol, phthanol.

Examples include methyl cellosolve, but methanol is particularly preferred.

The amount of alcohol used is preferably an amount that can dissolve the raw material halo-substituted nitrophenol at room temperature below the boiling point of the alcohol, or slightly longer than that, and is usually 50 to 50 parts per 100 parts of the halo-substituted nitrophenol.
200 parts (although halo-substituted nitrophenols generally have a high melting point).

It is preferable to avoid handling it in a molten state as it has poor thermal stability.)

As for the Raney nickel catalyst used in the reaction, a commercially developed paste may be used as it is, or it may be treated with acidic sodium saliva sulfate, acidic ammonium sulfite, etc. in a conventional manner to reduce the activity, and the amount used is... 0.1 to 20 parts, preferably 2 to 20 parts per 100 parts of substituted nitrophenols
There are 5 parts. Also.

The alkaline agent may be one or more necessary for the halo-substituted aminophenol produced in one reaction to become an alkali metal salt.1Usually, for 1 mole of the halo-substituted nitrophenol,
About 0.9 to 1.1 mol is used. As the alkali agent, sodium hydroxide, magnesium oxide, magnesium hydroxide, potassium hydroxide, sodium carbonate, calcium hydroxide, etc. are used, but sodium hydroxide is particularly preferred.

The alkaline agent may be added to the reactor all at once or may be added continuously in parallel with the supply of the nitro compound. Although the alkaline agent may be added in solid form, it is usually added as an aqueous solution.

Further, specific examples of cyano compounds or thiazoles include:
Diaminomaleonitrile, Koba/if nitrile, dimethyl cyanamide, β-aminopropionitrile, α-cyanoacetamide, methyleneaminoacetonitrile, 5-
Examples include cyanopyridine, iminodiacetonitrile, cyanamide, dianediamide, and 2-aminothiazolebenzothiazole, but cyanamide is particularly preferred.

Dicyandiamide, 2-aminothiazole, and benzothiazole may be used in combination, and the amount used is 0.00 parts per 100 parts of the eight-substituted nitrophenol.
5 to 10 parts are used.

To prepare an aqueous medium containing a Raney nickel catalyst, 77 compounds or thiazoles, and an alkaline agent, water is usually used as a medium, but for example, water containing a water-soluble alcohol such as methanol, ethanol, or propanol may be used. Good too.

in reaction. Although the hydrogen pressure is arbitrary, it is usually 0.5 to 1.
20 Kf/crIL2 Preferably 2-10 Akebono
2 and 1 reaction source temperature is from room temperature to 150°C, preferably from 60 to 90°C. The reaction time is determined by the time for supplying the alcoholic solution of the I--substituted nitrophenol, and is usually 2 to 10 hours.

By the method of the present invention, the reaction solution obtained is separated from the catalyst, the alcohol is removed by distillation, and the target I/B-substituted aminophenols can be easily obtained by neutralizing with an acid and distributing the product. .

The method of the present invention produces fewer by-products due to dehalogenation reactions, nuclear hydrogenation reactions, etc., and uses Raney nickel catalyst, which has high charging efficiency and is easily available as an inexpensive catalyst. This is an extremely advantageous method for producing aminophenols.

Example The method of the present invention will be explained in more detail by way of examples.

Example 1 Raney Nickel 101 in an autoclave. 100 f of a 20% caustic soda aqueous solution of dicyandiamide S and QfS was added, the hydrogen pressure was adjusted to 8 KPkn2, and the temperature was raised to 85° C. with stirring.

A solution of Li'C', 2+ 6-cyclo-4-nitrophenol 1a4ft and methanol 6Gf (75d) was injected into an autoclave using a pressurized injection pump over a period of S time to perform a reaction.Hydrogen absorption After the completion of the reaction, aging was carried out at the same temperature and pressure for another 20 minutes, and then cooled to room temperature.The composition of the reaction solution determined by gas chromatography was 2,6-dichloro-4-aminophenol (target product). 99-8%, 2-/Clue 4-aminophenol 0.02%, 2.6-dichloro-4-aminocyclohexanol 0.18%.

After the catalyst was separated from the furnace, it was neutralized with 55% hydrochloric acid 52.51, and the precipitated crystals were collected with P, washed with water, and dried to obtain 2,6-dichloro-4-aminophenol 862 with a purity of 99.9. Ta. This was a yield of 96.6% of theory.

Example 2 In an autoclave, instead of 3.01 of dicyandiamide in Example 1, 1.0 of 2-aminothiazole was added! ii
The reaction was carried out in the same manner as in Example 1 except that + was added. The composition of the reaction solution determined by gas chromatography after the reaction was completed was 2,6-dichloro-4-aminophenol (
Target product) 99.7%, 2-chloro-4-aminophenol 0.2%, and 2,6-dichloro-4-aminocyclohexanol 0.1%.

Example 3 57.2 r of Raney nickel 8.02 dicyandiamide a, of, s 5% aqueous solution of caustic soda was added to an autoclave, the hydrogen pressure was adjusted to 10 KPZ leap 2, and the temperature was raised to 80°C. Next, 2-chloro-4-nitrophenol 86.75
A solution of 9 dissolved in 60 g of methanol was injected into the autoclave in the same manner as in Example 1 over a period of 2.5 hours. After stopping hydrogen absorption, aging was carried out at the same temperature and pressure for 20 minutes to complete the reaction. The composition of the reaction solution determined by gas chromatography was 99.7% of 2-chloro-4-aminophenol (target product), 0.1% of 4-aminophenol, and 4% of 4-aminophenol.
-aminocyclohexanol Q, i%, 2-chloro-4
-aminocyclohexanol 0.1%. After removing the catalyst from the reaction solution, the purity was reduced to 99 in the same manner as in Example 1.
- 9% of 2-chloro-4-aminophenol 681 was obtained. This was a yield of 95% of theory.

Example 4 In Example 1, 2-chloro-4-nitrophenol 6 was substituted for t+ of 2,6-dichloro-4-nitrophenol 1041.
The reaction was carried out in the same manner as in Example 1 except that methylphenol 94.25 SF was used. The composition of the reaction solution determined by gas chromatography at the end of the reaction was 2-chloro-4-
Amino-6-methylphenol (target product) qq, q%,
The nuclear hydrogenation content was 0.1 h. The reaction solution was treated in the same manner as in Example 1 to obtain 2-chloro-4-amino-
6-Methylphenol was obtained in 97% of theory.

Effects of the invention It has become possible to produce halo-substituted aminophenols in high yields with low by-products due to dehalogenation, nuclear hydrogenation, etc., using inexpensive and easily available Raney nickel catalysts, and with high productivity. .

Claims (1)

[Claims] 1. A method for producing halo-substituted aminophenols, which comprises supplying an alcoholic solution of halo-substituted nitrophenols under hydrogen pressure to an aqueous medium containing a Raney nickel catalyst, a cyano compound or thiazole, and an alkali agent, and reducing the hydrogen with hydrogen.