JPS5850993B2 - Method for producing 4↓-alkoxycarbonyl↓-3,5↓-dimethylphthalic anhydride - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing 4-alkoxycarbonyl-3,5-dimethylphthalic anhydride.

4-Alkoxycarbonyl-3,5-dimethylphthalic anhydride is a 6,8-dimethyl-4-hydroxymethyl-1-phthalazine-twocarboxylic acid that is effectively used for the prevention of arteriosclerotic diseases or thrombotic diseases. It is a substance useful as a raw material intermediate for synthesizing alkyl esters.

The present inventors conducted research on an efficient method for producing 4-alkoxycarbonyl 3,5-dimethylphthalic anhydride, and found that by treating 3,5-dimethyltrimellitic acid trialkyl ester with concentrated sulfuric acid, 1 It has been found that 4-alkoxycarbonyl-3,5-dimethylphthalic anhydride can be produced almost quantitatively in this process.

This knowledge is based on the fact that it is practically impossible to obtain anhydride and phthalic acid by treating phthalic acid ester, which is a compound that does not have a substituent on the benzene nucleus, in the same manner as the method of the present invention. This is completely unpredictable.

The present invention will be explained in detail below.

The method of the present invention is carried out by simply treating 3,5-dimethyltrimellitic acid trialkyl ester with concentrated sulfuric acid, and the concentrated sulfuric acid to be used is at least 80% (wt) or more. It is necessary to have a high O concentration, and the higher the concentration, the better the yield can be obtained.

Further, it is possible to use fuming sulfuric acid if necessary.

However, when using extremely high concentrations, it is necessary to take into consideration that undesirable results such as side reactions may occur, so it is better to avoid using highly concentrated fuming sulfuric acid alone. .

Usually, commercially available industrial concentrated sulfuric acid (approximately 95 wtφ) is sufficient, and when using fuming sulfuric acid in combination, it is desirable to use a solution with an SO3 concentration of 120 wt% or less.

The amount of sulfuric acid to be used is desirably at least 1:1 (by weight) to the raw material trialkyl ester, based on the above-mentioned commercially available concentrated sulfuric acid, and the larger the amount used, the higher the yield can be obtained.

Although it depends on other reaction conditions, the highest yield is generally achieved at about 4 times the amount.

Of course, if fuming sulfuric acid is used in combination, the above amount will vary slightly depending on its concentration.

The reaction is carried out under mild conditions.

Heating to an excessively high temperature must be avoided since it may cause adverse effects such as undesirable side reactions.

Generally, it is appropriate to conduct the reaction at a temperature of about room temperature to 80°C, preferably 30 to 60°C.

A reaction time of about 1 to 2 hours is sufficient under normal conditions.

The yield of the final anhydride mainly depends on the concentration of sulfuric acid used, the amount, the reaction temperature, etc., but if it is carried out within the above-mentioned preferred range, a value of 90% or more can be obtained. The results are almost quantitative.

Since the liquid after the reaction is a mixture in which a high concentration of sulfuric acid coexists, it is necessary to separate the target product by an appropriate method, but according to the findings of the present inventors, the obtained reaction mixture can be washed in cold water. It was found that the target product and sulfuric acid could be effectively separated by pouring into the solution.

In the case of phthalic anhydride, which has a similar structure to the compound of the present invention, if it is mixed with water, even cold water, it undergoes hydrolysis quickly and turns into phthalic acid. Reference) 4-alkoxycarbonyl-3,5 of the present invention
- In the case of dimethyl phthalic anhydride, it is difficult to undergo hydrolysis and is stable not only in pure water but also in acidic water in which a fairly high concentration of sulfuric acid coexists. Ta.

In the method of the present invention, when the reaction mixture is poured into cold water, 4-alkoxycarbonyl-3,5-dimethylphthalic anhydride precipitates as crystals, so usually the target product can be easily obtained by separating the crystals. It becomes possible.

However, the means for obtaining the target product from the reaction mixture is not necessarily limited to the above-mentioned methods, and appropriate methods such as extraction can be used as necessary.

In the method of the present invention, the target product, 4-alkoxycarbonyl-3,5-dimethylphthalic anhydride, is stable and does not undergo hydrolysis during post-treatment operations.

The method of the present invention is an industrially valuable method because it is easy to operate, does not require special equipment, and can provide a high yield of the desired product in a short time.

Examples are listed below.

Example 1 4.00 g of concentrated sulfuric acid (95 fb) was ice-cooled, and 1.0 CBi' of 4-ethoxycarbonyl-3,5-dimethylphthalate dimethyl ester was gradually added thereto while stirring.

After the addition was complete, the reaction mixture was continued to be stirred at room temperature for 1 hour and then poured into water.

The precipitated white solid substance was separated by furnace and recrystallized using isopropyl alcohol.

Crystals o, sog having a melting point of 78-80°C were obtained.

This product was confirmed to be 4-ethoxycarbonyl-3,5-dimethylphthalic anhydride based on data such as NMRlIR and elemental analysis.

Yield 95% Example 2 The treatment was carried out in the same manner as in Example 1 except that the amount of concentrated sulfuric acid was 10.00 g.

The reaction was completed in 40 minutes, and 4-ethoxycarbonyl-3,
0.81 J' of 5-dimethylphthalic anhydride (yield: 96 pieces) was obtained.

Example 3 The treatment was carried out in the same manner as in Example 1 except that the amount of concentrated sulfuric acid was changed to 2.51.

The reaction was completed in 1.5 hours, and 4-ethoxycarbonyl-
3,5-dimethylphthalic anhydride 0.76 g (yield 90
% )was gotten.

Example 4 In the same manner as in Example 3, the reaction was carried out at a temperature of 50°C. The reaction was completed in 40 minutes, and 0.79 g of 4-ethoxycarbonyl-3,5-dimethylphthalic anhydride (yield 94 buns) were obtained.

Example 5 Instead of the concentrated sulfuric acid used in Example 1, fuming sulfuric acid 1.
The treatment was carried out using a mixture of 32.9 and 2.68 g of concentrated sulfuric acid, but in the same manner as above.

The reaction was completed in 30 minutes, and 4-ethoxycarbonyl-3,
5-dimethylphthalic anhydride 0.80 g (yield 95 g)
was gotten.

Examples 6 to 8 The results of experiments conducted in the same manner as in Example 1 by changing the amount of concentrated sulfuric acid used, reaction temperature, and reaction time as shown in the table below are shown in the table below.

Example 9 Instead of the concentrated sulfuric acid used in Example 1, fuming sulfuric acid (6
The treatment was carried out in the same manner except for using 1.00 g of 0%).

In a reaction time of 10 minutes, 4-ethoxycarbonyl-3,5-
0.70 g (yield: 84 buns) of dimethyl phthalic anhydride was obtained.

Example 10 In place of the 4.00 g of concentrated sulfuric acid used in Example 1, water was added thereto to adjust the sulfuric acid concentration to 90φ, and the other treatment was carried out in the same manner.

The reaction was completed in 1.5 hours, and 4-ethoxycarbonyl-
3,5-dimethylphthalic anhydride 0.77g (91na)
was gotten.

(In addition, when the sulfuric acid concentration was adjusted to 80%, the yield was 61%.) Example 11 10.00 g of concentrated sulfuric acid was cooled on ice, and 3,5-dimethyltrimellitic acid was prepared with stirring. Triethyl ester 1. OOg was added slowly.

After the addition was complete, the reaction mixture was further stirred for 1 hour at room temperature and then poured into water.

The precipitated white solid substance was separated by furnace and recrystallized using isopropyl alcohol.

0.749 g of 4-ethoxycarbonyl-3,5-dimethylphthalic anhydride (yield: 96 g) was obtained.

Example 12 3,5-dimethyltrimellitate trimethylester was used in place of the 3,5-dimethyltrimellitate triethyl ester used in Example 11, and the other procedures were the same, resulting in white crystals o, sog was obtained.

This product showed a melting point of 129-131°C.

From the results of NMRlIR and elemental analysis, this product is
It was confirmed that it was 4-methoxycarbonyl-3,5-dimethylphthalic anhydride.

Yield: 96 Reference Example: 10.0 g of concentrated sulfuric acid (95%) was cooled on ice, and 1.01 g of dimethyl phthalate was gradually added thereto with stirring.
The reaction mixture was heated for 15 hours and then heated at 70° C. for 3 hours, and the resulting reaction mixture was cooled and poured into water.

0.679 phthalic acid (yield 78 g) was obtained, but no phthalic anhydride was obtained.

Claims (1)

[Claims] 1. 3,5-dimethyltrimellitic acid trialkyl ester represented by the general formula, □ (in the formula, R, R1, and R2 each represent a lower alkyl group) is treated with concentrated sulfuric acid to obtain a The resulting reaction product is poured into water to precipitate 4-alkoxycarbonyl-3,
A method for producing 4-alkoxycarbonyl-3,5-dimethylphthalic anhydride, which comprises obtaining 5-dimethylphthalic anhydride.