JPS6031818B2 - Method for producing aminophenyl isopropyl ether - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing aminophenylisopropyl ether* in high yield and high selectivity.

Aminophenol ethers such as aminophenyl isopropyl ether are useful as raw materials or intermediates for medicines, agricultural chemicals, fragrances, etc., and various production methods are known. For example, there is a method of producing aminophenyl alkyl ether by directly reacting aminophenol with an alkyl halide. However, in this method, as shown in the reaction formula below, in addition to the target aminophenyl alkyl ether (a), N-alkylaminophenol 'b} and N-alkylaminophenyl alkyl ether [c1] are created. , it was difficult to selectively produce only the aminophenyl alkyl ether in high yield. (In the formula, R,
is an alkyl group, and X is a halogen atom. ) To solve this problem, a method was proposed in which the amino group of '1} aminophenol was acetylated and protected as an acetamide group, the alkyl halide was reacted to etherify the acetamide group, and the acetamide group was then hydrolyzed (for example, Japanese Pharmaceutical Journal). , Vol. 74 (1954), pp. 872-875), ■ The hydroxyl group of aminophenol is converted to sulfochloride'
A method in which a sulfonic acid ester (OS02Ar) is prepared from this and then a metal alcoholate is reacted as an alkylating agent (for example, Japanese Pharmaceutical Journal, No. 7 Junnitrogen (1954)
(See pages 872-875); (See pages 334 to 334) were proposed.

However, method '1) requires a large number of steps and thus increases the production cost of the target aminophenylalkyl ether, and is not satisfactory as an industrial method.
Furthermore, in the method of [21, Legs], the by-products of N-alkylaminophenol and N-alkylaminophenyl alkyl ether cannot be sufficiently avoided, and the selectivity of aminophenyl alkyl ether is still low, resulting in poor yield. The problem was that the rate was low. On the other hand, as a method for producing phenol ether, a method is known in which phenol and an organic halide are produced in a mixed solvent of dichloromethane and water in the presence of quaternary ammonium bromide and sodium hydroxide (tetrahydrone, quaternary ammonium bromide, and sodium hydroxide). Volume 30, No. 1379-138
(See page 2, 1974).

However, although this method is suitable for producing corresponding phenol ethers from phenols such as phenol, 4-ten-butylphenol, 4-methoxyphenol, and nitrophenol, it is difficult to produce aminophenol ethers using aminophenol. This method was inappropriate as a production method, and the reaction hardly proceeded, resulting in hardly any of the desired aminophenophenols being obtained. The present inventors have conducted various studies to develop a method for obtaining high yields of aminophenylisopropyl ether, which is useful as a raw material for agricultural chemicals among aminophenol ethers, and found that aminophenol and halogenated isopropyl ether When reacting in the presence of a quaternary ammonium salt or phosphoium salt and an alkali metal hydroxide, if the reaction is carried out under substantially anhydrous conditions with an excess of isopropyl halide without using a normal organic solvent. It has been found that the purpose can be satisfied and the drawbacks of the conventional method can be overcome.

The present invention has been made based on this knowledge. That is, the present invention provides a benzyltrialkylammonium salt,
Aminophenol and isopropyl halide in the presence of at least one selected from benzyltrialkylphosphonium salts, benzyltriphenylphosphonium salts, tetraalkylammonium salts and tetraalkylphosphonium salts and an alkali metal hydroxide. Production of aminophenylysopropyl ether, which is characterized in that the reaction is carried out under substantially anhydrous conditions with an excess of isopropyl halide. The present invention provides a method.

The aminophenol used in the method of the present invention may be any of 2-aminophenol, 3-aminophenol and 4-aminophenol.

Further, the halogenated isopropyl is preferably one in which the halogen atom is chlorine or bromine, and particularly preferably chlorine. The quaternary salts used in the method of the invention are penzyltrialkylammonium salts, benzyltrialkylphosphonium salts, benzyltriphenylphosphonium salts,
Tetraalkylammonium salts and tetraalkylphosphonium salts, specific examples of which include penzyltrimethylammonium bromide, benzyltriethylammonium chloride and bromide, benzyltripropylammonium chloride, benzyltributylammonium chloride, benzyltrihexylammonium chloride,
Benzyltrioctylammonium chloride, benzyltributylphosphonium bromide, benzyltriphenylphosphonium chloride.

Lido, tetramethylammonium chloride, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrahexylammonium bromide, tetraoctylammonium chloride, cetyltrimethylammonium chloride, butyltriethylammonium Bromide, lauryl triethylammonium bromide,
Ethyltributylammonium bromide, isoptyltriptylammonium bromide, hexyltributylammonium bromide, octyltributylammonium bromide, lauryltributylammonium bromide,
Examples include methyltrioctylammonium chloride, tetrabutylphosphonium bromide, tributylhexylphosphonium bromide, and tributyloctylphosphonium bromide. In addition, anilinium salts such as benzyl N,N-dimethylanilinium chloride, benzyl N,N-diethylanilinium chloride, methyl N,N-dimethylanilinium chloride, octyl N,N-dimethylanilinium bromide, N-ethylpyridinium Bromide, N-isoamylpyridinium bromide,
When a quaternary salt such as a pyridinium salt such as N-octylpyridinium bromide is used, the reaction does not proceed at all and the object of the present invention cannot be achieved. The alkali metal hydroxides used in the method of the present invention include potassium hydroxide, sodium hydroxide, etc., and these are used in the form of solids such as granules, powders, and flakes.

The present invention is characterized in that the reaction is carried out under substantially anhydrous conditions using 2 mol or more of isopropyl halide per 1 mol of aminophenol without using a common organic solvent.

In this case, the isopropyl halide is converted into aminophenol 1
Unless the amount is 2 moles or more, the target aminophenylisopropyle 7l cannot be obtained in high yield and with high purity. Further, the reaction of the present invention needs to be carried out under substantially anhydrous conditions. Here, substantially anhydrous means 1
When producing one mole of aminophenol ether, theoretically one mole of water is produced, but this means that about 1 to 1.5 moles of water may be present. In the reaction of the present invention, the reaction temperature is suitably 0 to 150 oo, and 20 to 80 oo.
A range of oo is preferred. The reaction time is usually 1 to 2 field hours, preferably 5 to 1 hour. The amount of quaternary ammonium salt or phosphonium salt used is usually 0.01 to 0.1 times the mole of aminophenol,
Preferably it is 0.03 to 0.07 times the mole.

The appropriate amount of alkali metal hydroxide to be used is equimolar to the aminophenol, but the amount of the alkali metal hydroxide is 1.1 to 5.
It is preferable to use an excess in the sonic molar range of . In the method of the present invention, after the reaction is completed, excess alkali metal hydroxide is removed by filtration, etc., and excess isopropyl halide is purified using a conventional method to obtain highly pure aminophenyl isopropyl ether. can.

According to the present invention, aminophenylysop is produced by reacting aminophenol with isopropyl halide. When producing pyritether, the production of by-products can be almost completely suppressed and the desired aminophenylysopropylether can be obtained with high selectivity and yield, which is an excellent effect. Next, the present invention will be explained in more detail based on examples. Example 500 [Customer's glass autoclave contained 55.1 moles (0.5 moles) of 3-aminophenol, 150 moles (1.91 moles) of isopropyl chloride, and 60 moles of sodium hydroxide.
．． 6 days (1.5 mol) and 50% tetrabutylammonium bromide aqueous solution 9.7 days (tetrabutylammonium bromide 0.015 mol) were prepared (3 powders) and 70
The temperature was raised to 0.degree. C., and the reaction was carried out with stirring for 7 hours at a reaction pressure of 4 kg/me.

After the reaction was completed, the reaction solution was washed with water, and unreacted isopropyl chloride was then distilled off under normal pressure, followed by vacuum distillation to obtain 74.1 units of the desired 3-impropoxyaniline. The yield was 98.0% and the purity was 98.0%. Comparative Example 3 - Producing 3-impropoxyaniline in exactly the same manner as in the above example, except that isopropyl chloride was used in an equal mole (39.27 moles) to 55.1 moles (0.5 moles) of aminophenol. The yield was 55% and the purity was 97%.

Claims (1)

[Claims] 1 At least one selected from benzyltrialkyl ammonium salts, benzyl trialkylphosphonium salts, benzyl triphenylphosphonium salts, tetraalkyl ammonium salts, and tetraalkylphosphonium salts
In producing aminophenyl isopropyl ether by reacting aminophenol and isopropyl halide in the presence of seeds and alkali metal hydroxide, at least 2 moles of isopropyl halide are used per mole of aminophenol, and substantially A method for producing aminophenyl isopropyl ether, which comprises carrying out the reaction without a solvent under anhydrous conditions.