JP2000103771A - Production of 4,6-diacylaminoresorcinol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for industrially advantageously producing a 4,6-diacylaminoresorcinol useful for e.g. pharmaceutical preparations, a grochemicals or as an intermediate for functional pigments without taking the form of a nitro compound and via a route based on a raw material and reaction mechanism different from the conventional by hydrolyzing a specific dialkylbenzobisoxazole. SOLUTION: This method is conducted by hydrolyzing a dialkylbenzobisoxazole e.g. 2,6-dimethylbenzo[1,2-d; 5,4-d']bisoxazole} pref. in an acid aqueous solution e.g. hydrochloric acid aqueous solution with a concentration of 1 to 85 wt.% pref. at 5 to 120 deg.C, thus obtaining the objective compound (e.g. a 4,6-diacylaminoresorcinol) of formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for industrially and advantageously producing 4,6-diacylaminoresorcinols.

[0002]

[Prior Art] The following equation (2)

Embedded image (R is an alkyl group having 1 to 3 carbon atoms)
The following two methods are known as methods for producing diacylaminoresorcins.

[0003] Method 1 is described in "Heller, Sourlis; Chem. Be.
r., 43 (1910), 2584 ". In this method, 4,6-dinitroresorcin is reduced with tin and hydrochloric acid in the presence of acetic anhydride, whereby
(2) 4,6-diacylaminoresorcinol is obtained.
The reaction formula at this time is represented as follows.

[0004]

Embedded image

[0005] Method 2 is a method described in Japanese Patent Application Laid-Open No. 10-168041 filed by the present applicant. In this method 2, dioxime is prepared according to the following reaction formula.
4,6-diacylaminoresorcinol (2) is obtained from (a) by Beckmann rearrangement reaction.

[0006]

Embedded image

[0007]

In the above-mentioned method 1, 4,6-dinitroresorcin as a starting material can be obtained by dinitrating resorcinol. Since it is difficult to introduce a nitro group into the compound, the yield of 4,6-dinitroresorcin is low, and a trinitro compound having a risk of explosion is inevitably produced as a by-product. Note that "Macromolecules 1
981, 14, 909-915 "shows a reaction for obtaining 4,6-dinitroresorcin from resorcinol diacetate, but it is inevitable that a trinitro compound is by-produced. Therefore, it is strongly desired to develop a method for producing 4,6-diacylaminoresorcin represented by the formula (2) without using a nitro compound as a raw material.

[0008] Method 2 is advantageous over method 1 because it is a method that does not undergo nitration.
It may not always be able to meet market demands. In the market, there are several sources of raw materials that can be selected, and considering the stable availability of raw materials, cost, degree of purification, etc., if production is not performed most advantageously, industrial implementation itself Is not possible. It is also important to find a method that does not undergo nitration other than Method 2 from the viewpoint of enrichment of technology.

In this background, the present invention is industrially advantageous in that 4,6-diacylaminoresorcinols can be obtained without a nitro compound and by a route based on a different raw material source and reaction mechanism. It is intended to provide a simple manufacturing method.

[0010]

The process for producing 4,6-diacylaminoresorcinols of the present invention is represented by the following formula (1):

Embedded image (R is an alkyl group having 1 to 3 carbon atoms) by subjecting a dialkylbenzobisoxazole represented by the following formula (2) to a hydrolysis reaction.

Embedded image (R is the same as above), characterized in that 4,6-diacylaminoresorcinols are obtained.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

The target product, 4,6-diacylaminoresorcin of formula (2), can be obtained by subjecting a starting material, dialkylbenzobisoxazole of formula (1), to a hydrolysis reaction.

The hydrolysis reaction at this time is carried out in an acidic aqueous solution, for example, in an aqueous solution of a mineral acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or in an aqueous solution of an organic acid such as acetic acid, formic acid or oxalic acid. .

At this time, the concentration of the acid (mineral acid or organic acid) is preferably 0.1 to 90% by weight, particularly preferably 1 to 85% by weight. Particularly when a strong acid such as hydrochloric acid or sulfuric acid is used, its concentration is 0.1 to 15% by weight, especially 1 to 10% by weight
It is preferable that When the concentration of the acid is too low, the hydrolysis reaction does not proceed smoothly. On the other hand, when the concentration of the acid is too high, the target product is further hydrolyzed and the yield of the target product decreases.

The reaction temperature ranges from 0 to 150 ° C., preferably from 5 to 12
The temperature is preferably set to 0 ° C. Especially when using mineral acids,
The temperature is preferably from 0 to 70 ° C, particularly preferably from 5 to 50 ° C, and usually a temperature condition near room temperature is employed. When the reaction temperature is too low, the reaction does not proceed sufficiently. On the other hand, when the reaction temperature is too high, the target product is further hydrolyzed and the yield of the target product decreases.

Even in the above-mentioned ranges of the acid concentration and the reaction temperature, depending on the combination of the kind of the acid, the concentration of the acid, the reaction temperature and the reaction time, the reaction conditions are too strong and the target product tends to be further hydrolyzed. . For example, under conditions where dialkylbenzobisoxazoles are heated in a 20% by weight aqueous hydrochloric acid solution at 90 to 100 ° C. for 3 hours, the 4,6-diacylaminoresorcins once formed are further hydrolyzed, May be 6-diaminoresorcin.

In any case, the reaction proceeds by opening one of the oxazole rings of the dialkylbenzobisoxazoles and subsequently opening the remaining oxazole rings to form 4,6
-Diacylaminoresorcin is formed. If the hydrolysis reaction proceeds further, 4,6-diaminoresorcin is generated. The degree of progress of the reaction can be confirmed by simple analytical means such as thin-layer chromatography and high-performance liquid chromatography, and 4,6-diacylaminoresorcinols are selectively produced using such analytical means. It is desirable to find the reaction conditions. This allows
4,6-Diacylaminoresorcinols can be isolated with high yield.

The 4,6-diacylaminoresorcins of the formula (2) formed by the above hydrolysis reaction are hardly soluble in acidic aqueous solutions (organic acid aqueous solution, mineral acid aqueous solution) and organic solvents, and thus precipitate as white crystals. I do. If further purification is necessary, the crystals may be washed with water, an aqueous acidic solution, an organic solvent or the like.

As the raw material, the dialkylbenzobisoxazole of the formula (1) can be obtained by any method.

One method for obtaining the starting dialkylbenzobisoxazoles of the formula (1) is to use the corresponding
This is a method in which the dioximes represented by (a) are reacted in the presence of a catalyst such as polyphosphoric acid.The reaction solution after the reaction is neutralized and then extracted with an organic solvent, or the reaction solution is poured into an alkaline aqueous solution. By crystallization, dialkylbenzobisoxazoles can be isolated. This method has been filed by the present applicant as Japanese Patent Application No. 9-248237.

[0021]

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<Use> Formula obtained by the method of the present invention
The 4,6-diacylaminoresorcinols of (2) are useful as pharmaceuticals, agricultural chemicals, intermediates of functional dyes, high heat-resistant and high-strength polymer raw materials, and in particular, the following corresponding to polybenzobisoxazole monomers: It is important as a raw material for producing 4,6-diaminoresorcin represented by the formula (b).

[0023]

Embedded image

[0024]

The present invention will be further described with reference to the following examples.

Example 1 <Synthesis of Starting Dialkylbenzobisoxazoles> After heating 823.2 g of polyphosphoric acid to 90 ° C., the dioxime represented by the above formula (a) and in which R is a methyl group (ie, 1,2)
1 '-(4,6-dihydroxy-1,3-phenylene)
235.2 g of bis-ethanone dioxime at 90 to 110 ° C
, And reacted at 95-100 ° C. for 3 hours. After the reaction was completed, the reaction solution was cooled and then slowly poured into 5451 g of a cold aqueous solution of sodium hydroxide having a concentration of 12.95% by weight. The precipitated crystals were separated by filtration, washed with water, and dried. The yield of the obtained crude 2,6-dimethylbenzo [1,2-d; 5,4-d '] bisoxazole was 97.42%.

The crude 2,6-dimethylbenzo [1,
After dissolving 2-d; 5,4-d '] bisoxazole in a mixed solvent of water and acetone, the mixture was treated with activated carbon, and the obtained solution was concentrated and cooled. As a result, needle crystals were deposited. The crystals were filtered off, washed with water and dried. This allows
2,6-dimethylbenzo [1,2-
d; 5,4-d '] bisoxazole was obtained. The recrystallization yield was 81.1%.

<Synthesis of 4,6-diacylaminoresorcinol> The 2,6-dimethylbenzo [1,2-
d; 5,4-d '] bisoxazole 0.50 g (2.66 mmol
l) and 8 ml of a 0.5N aqueous hydrochloric acid solution at room temperature for 24 hours.
The reaction was performed by stirring for hours. After confirming the completion of the reaction by thin-layer chromatography, the crystals were separated by filtration, washed with water and then with methanol, and dried under reduced pressure to give 0.55 g.
Was obtained as white crystals. From the result of IR analysis,
It was confirmed to be 4,6-diacetylaminoresorcin. The yield was 92.3%.

Example 2 Example 1 was repeated except that sulfuric acid was used instead of hydrochloric acid. That is, 2,6-dimethylbenzo [1,2-d;
5,4-d '] bisoxazole 0.50 g (2.66 mmol)
A mixture with 8 ml of 0.5N sulfuric acid aqueous solution was reacted by stirring at room temperature for 24 hours, and completion of the reaction was confirmed by thin layer chromatography. The crystals were separated by filtration, washed with water and then with methanol, and dried under reduced pressure to obtain 0.58 g of white crystals. From the results of IR analysis, the crystals were confirmed to be 4,6-diacetylaminoresorcin. The yield was 97.4%.

Example 3 Example 1 was repeated except that phosphoric acid was used instead of hydrochloric acid and the reaction time was changed to 23.5 hours. That is, 2,
The reaction was carried out by stirring a mixture of 0.50 g (2.66 mmol) of 6-dimethylbenzo [1,2-d; 5,4-d '] bisoxazole and 8 ml of a 50% by weight phosphoric acid aqueous solution at room temperature for 23.5 hours. The completion of the reaction was confirmed by thin-layer chromatography. The crystals were separated by filtration, washed with water and then with methanol, and dried under reduced pressure to obtain 0.38 g of pink crystals. From the results of IR analysis, the crystals were confirmed to be 4,6-diacetylaminoresorcin. The yield was 63.8%.

Example 4 Example 1 was repeated except that phosphoric acid was used instead of hydrochloric acid. That is, 2,6-dimethylbenzo [1,2-d;
5,4-d '] bisoxazole 0.50 g (2.66 mmol)
A mixture with 8 ml of a 2.5% by weight phosphoric acid aqueous solution was reacted by stirring at room temperature for 24 hours, and the completion of the reaction was confirmed by thin layer chromatography. The crystals were separated by filtration, washed with water and then with methanol, and dried under reduced pressure.
g of white crystals were obtained. From the results of IR analysis, the crystals were confirmed to be 4,6-diacetylaminoresorcin. The yield was 85.6%.

Example 5 <Synthesis of 4,6-diacylaminoresorcinols> 2,6
A mixture of 9.41 g (50 mmol) of -dimethylbenzo [1,2-d; 5,4-d '] bisoxazole and 47.21 g of an 80% by weight aqueous acetic acid solution was heated under reflux for 3 hours. After cooling to room temperature, the crystals were filtered off, washed first with water and then with methanol and dried. This
10.96 g of white crystals were obtained. From the results of IR analysis, the crystals were confirmed to be 4,6-diacetylaminoresorcin. The yield was 97.73%.

<Synthesis of 4,6-diaminoresorcinol> 7.86 g of 4,6-diacetylaminoresorcinol obtained above
(35 mmol), a mixture of 55.13 g of a 20% strength by weight aqueous hydrochloric acid solution and 0.73 g of stannous chloride dihydrate,
The reaction was stirred at 110 ° C. for 3 hours. After cooling to room temperature, the crystals were filtered off, washed with a 17.5% by weight aqueous hydrochloric acid solution, then with acetone and dried. This gives 7.
30 g of white crystals were obtained. From the result of IR analysis, it was confirmed that the crystals were 4,6-diaminoresorcinol dihydrochloride. The yield was 97.72%.

Example 6 Example 5 was repeated except that formic acid was used instead of acetic acid. That is, 2,6-dimethylbenzo [1,2-d;
A mixture of 0.50 g (2.66 mmol) of 5,4-d '] bisoxazole and 8 ml of a 80% by weight aqueous solution of formic acid was heated under reflux for 30 minutes. After cooling to room temperature, the crystals were filtered off, washed first with water and then with methanol and dried. This gave 0.53 g of white crystals. From the results of IR analysis, the crystals were confirmed to be 4,6-diacetylaminoresorcin. The yield was 89.0%.

Example 7 2,6-dimethylbenzo [1,2-d; 5,4-d ']
A mixture of 0.50 g (2.66 mmol) of bisoxazole, 7.42 g of water and 0.64 g of oxalic acid dihydrate was heated under reflux for 30 minutes. After cooling to room temperature, the crystals were filtered off, washed first with water and then with methanol and dried.
This gave 0.56 g of white crystals. This crystal has an IR
The result of the analysis confirmed that the substance was 4,6-diacetylaminoresorcin. The yield was 94.0%.

Reference Example 1 <Synthesis of 4,6-diaminoresorcinol> 9.41 g (50 mmol) of 2,6-dimethylbenzo [1,2-d; 5,4-d '] bisoxazole, hydrochloric acid having a concentration of 20% by weight Aqueous solution 7
A mixture of 5.49 g and stannous chloride dihydrate 0.81 g in 1
The mixture was stirred and reacted at 00 to 105 ° C for 3 hours. After cooling to room temperature, the crystals were filtered off, washed with a 17.5% by weight aqueous hydrochloric acid solution, then with acetone and dried. This gave 10.46 g of white crystals. From the result of IR analysis, it was confirmed that the crystals were 4,6-diaminoresorcinol dihydrochloride. The yield was 98.18%.

[0036]

According to the present invention, 4,6-diacylaminoresorcinols can be industrially advantageously produced without a nitro compound and by a route based on a different raw material source and reaction mechanism. be able to.

Claims (2)

[Claims] (1) The following formula (1): (R is an alkyl group having 1 to 3 carbon atoms) by a hydrolysis reaction of a dialkylbenzobisoxazole represented by the following formula (2): (R is the same as above). A process for producing 4,6-diacylaminoresorcinols, wherein 2. The process according to claim 1, wherein the hydrolysis of the compound of the formula (1) to the compound of the formula (2) is carried out in an acidic aqueous solution.