JPH01299245A - Production of squalic acid - Google Patents

Abstract

PURPOSE:To advantageously obtain squalic acid useful as an intermediate of laser sensitive dye, etc., in a simple process, by reacting 3-hydroxy-3- cyclobutenediones with bromine in an aqueous liquid to brominate 4-position of the above-mentioned compound and hydrolyzing the resultant product. CONSTITUTION:3-Hydroxy-3-cyclobutenedione or base thereof, preferably alkali metal salt thereof is reacted with bromine in an aqueous liquid at 0-50 deg.C, preferably 0-30 deg.C and the resultant 4-bromo-3-hydroxy-3-cyclobutenedione is hydrolyzed at 70-150 deg.C, preferably 70-120 deg.C using a strong acid, especially sulfuric acid without isolating to industrially and economically obtain squalic acid useful also as an intermediate for medicine in process shortened because of obviating filtration process of the above-mentioned intermediate giving inferior operation environment and in simplified process and improved operation environment, etc., owing to be free from using a halogenated hydrocarbon harmful to human bodies.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing squaric acid, which is useful as a synthetic intermediate for laser-sensitive dyes, pharmaceuticals, and the like.

Conventional techniques and problems to be solved A method for producing squaric acid is, for example, a method using hexachlorobutadiene as a raw material (U.S. Pat. No. 4,104.30).
No. 8), method of manufacturing from ketene derivatives (JOC,
44, 1208, (1979) Nat), -Production method by electroreductive tetramerization reaction of carbon oxide (US Patent 3.83)
3.489), but the synthetic intermediate has an explosion risk (U.S. Pat. No. 4, 104.308).
, the raw materials are expensive, difficult to obtain, or require a high-pressure reactor.

It is also known that squaric acid can be produced from 3-hydroxy-3-cyclobutenedione by the following reaction [
Herpechi Power, Kimi Power, Acta.

61, (5), 1784 (1978)). This method produces hydrogen bromide white smoke when isolating the intermediate 4-bromo-3-hydroxy-3-cyclobutenedione;
Furthermore, it is very troublesome to handle on an industrial scale, such as separating squaric acid from concentrated hydrochloric acid after hydrolysis.

Yield: 73% Means for solving the problem As a result of studying the method for producing squaric acid from 3-hydroxy-3-cyclobutenedione, when brominating 3-hydroxy-3-cyclobutenedione,
- It has been found that water can be used as a solvent in place of 110-generated hydrocarbons such as methylene chloride and ethylene dichloride used in boat fishing, and inert organic solvents. This allows the reaction intermediate 4-bromo-3-hydroxy-
A method has been completed in which strong acids such as concentrated sulfuric acid, hydrogen chloride gas, and phosphoric acid are added to the reaction solution to subject it to a hydrolysis reaction without isolating 3-cyclobutenedione.

According to the present invention, squaric acid can be produced by reacting 3-hydroxy-3-cyclobutenedione with bromine in an aqueous liquid and hydrolyzing the reaction mixture.

The amount of water employed in the bromination reaction is 1 to 5, based on 3-hydroxy-3-cyclobutenedione or its salt.
Use 0 times. Preferably 2 in terms of productivity and stirring efficiency.
~10 times the amount is used.

The amount of bromine used in the reaction is 0.1 to 2.0 equivalents relative to 3-hydroxy-3-cyclobutenedione, but in order to consume enough raw materials and suppress side reactions caused by excess bromine, A range of 1.0 to 1.2 equivalents is preferred. The reaction is carried out at a temperature of 0-50<0>C, preferably 0-30<0>C.

3-Hydroxy-3-cyclobutenedione to be subjected to the bromination reaction can be used in either its free form or its salts, and salts with alkali metals or alkaline earth metals and salts with various organic bases are used. , K which is soluble in water solvent and the reaction proceeds rapidly.

Alkali metal salts such as Na are preferred.

The bromination reaction solution can be directly subjected to a hydrolysis reaction by adding a strong acid, but it is preferable to remove excess bromine. Bromine and generated hydrobromic acid are removed by heating at 30 to 70°C and reducing pressure.

For hydrolysis reactions, strong acids such as hydrogen chloride, hydrogen bromide,
In addition to mineral acids such as sulfuric acid and phosphoric acid, p-toluenesulfonic acid and methanesulfonic acid can be used, but sulfuric acid is most preferred because it is inexpensive and easy to handle.

The concentration of strong acids used is 10 to 95%, and the amount used is 4
-Bromo-3-hydroxy-3-cyclobutenedione is used in an amount of 0.5 to 50 equivalents, preferably 1 to 30 equivalents at a concentration of 10 to 70%. The reaction is 70-150
It is preferably carried out at a temperature of 70 to 120°C.

The obtained squaric acid precipitates in the hydrolysis reaction system, so it can be collected by filtration by a conventional method and purified if necessary to obtain high-purity squaric acid.

Effects of the Invention According to the present invention, it is possible to produce squaric acid without isolating 4-bromo-3-hydroxy-3-cyclobutenedione, and as an industrial production method, it is possible to simplify the process and improve the work environment. Demonstrates excellent improvement effects. In addition, since isolation of the intermediate is not required, the filtration process, which produces a strong pungent odor of hydrogen bromide and creates a poor working environment, is not necessary, and the process is also shortened. This method is economically advantageous because it avoids the use of halogenated hydrocarbons, which are harmful to the human body, and does not use organic solvents.

Example Hereinafter, the present invention will be specifically explained with reference to Examples.

Example 1 19.5 g (0,163 mol) of 3-hydroxy-3-cyclobutenedione sodium salt and 117 ml of water were added to 50
Pour 0ffl into a 14-meter flask and add 27.3 bromine from dropping funnel L while stirring under N.
g (0,171 mol) was added dropwise over 3 hours. During this time,
The temperature was maintained at 15 to 20°C, and the mixture was aged for 2 hours after the dropwise addition of bromine was completed. After the reaction was completed, the mixture was treated under reduced pressure at an internal temperature of 50° C. with gentle shaking for 3 hours to remove excess bromine and a portion of the generated hydrogen bromide. Add 78g of concentrated sulfuric acid to this liquid.
(0,795 mol) was added to adjust the sulfuric acid concentration to 4 Qwt%, and then heated and stirred at 90 to 95°C for 10 hours.
The mixture was cooled to 0° C. to sufficiently precipitate the generated squaric acid. The precipitate was collected by filtration, washed with acetone, and dried to obtain 17.5 g of squaric acid. Yield 94.4% HPLC purity 9
9.3wt%. Honjima can be recrystallized to a higher purity if necessary.

Examples 2 to 4 The same treatments as in Example 1 were carried out except that the amount of sulfuric acid used was changed, and the results shown in the table below were obtained.

Comparative Example 1 19.5 g (0,163 mol) of 3-hydroxy-3-Schiff robenedione sodium salt and 200 ml of 1,2-dichloroethane were placed in a 500 ml 4-tube flask, and the internal temperature was brought to 50°C while stirring under N. Keep at ℃, bromine 2
7.3 g (0,171 mol) was added dropwise over 2 hours. During this time, the internal temperature was maintained at 15 to 20°C.

After further aging at the same temperature for 2 hours, residual bromine and generated hydrogen bromide were removed under reduced pressure with slight reflux at an internal temperature of 50°C, and then cooled to 20°C and the precipitated product was collected by filtration. 1.
Washed with 2 dichloroethane. During filtration, white smoke of hydrogen bromide rose, and even after washing with 1.2 dichloroethane, a strong hydrogen bromide odor remained.

Put this filtered material into a 50 Qm1 reaction flask, and add 5 Qm
Add 234 g of wt% sulfuric acid and heat to 90-95°C.

After heating and stirring for 10 hours, it was cooled to 30°C, and the precipitated product was filtered, washed with acetone, and dried to obtain squaric acid 17.
3 g was obtained.

Yield: 93.4% HPLC purity: 99.1% Comparative Example 2 Comparative Example 10 Above: The reaction was carried out in the same manner as Comparative Example 1 except that dichloromethane was used instead of 2-dichloroethane. Although bromine and hydrogen bromide were removed, there was a strong odor of bromine and hydrogen bromide when the product was filtered.

Claims (1)

[Claims] 4-bromo-produced by reacting 3-hydroxy-3-cyclobutenedione or its salts with bromine in an aqueous liquid
A method for producing squaric acid, which comprises hydrolyzing 3-hydroxy-3-cyclobutenedione.