JP2002060366A - Acetal hydrolysis method - Google Patents

Abstract

(57) Abstract: The present invention relates to a method for hydrolyzing an acetal, in particular, benzyloxyacetaldehyde dialkyl acetal. SOLUTION: In the presence of a phosphoric acid catalyst, hydrolyze an acetal, especially benzyloxyacetaldehyde dialkyl acetal.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for hydrolyzing an acetaldehyde dialkyl acetal, and particularly to hydrolyzing a benzyloxyacetaldehyde dialkyl acetal in order to produce benzyloxyacetaldehyde useful as an intermediate for pharmaceuticals such as anti-AIDS agents. It relates to the method of disassembly.

[0002]

2. Description of the Related Art A method for hydrolyzing an acetal such as diethyl acetal in the presence of an acid catalyst is well known. Various compounds are also known as acid catalysts, for example, acetic acid [Bull. Soc. Chim. Fr. , (5), 82
7 (1987)], acetic anhydride [J. Chem. Soc.
Perkin, (9), 1189 (1995)], trifluoroacetic acid [Heterocycles, 43, 26].
87 (1996)] and concentrated sulfuric acid [J. Labelled
Comp. Radiopharm. , 22 (3), 22
9 (1985)].

[0003]

However, when an organic acid such as acetic acid is used, a large excess of the acid with respect to the acetal is required, and the operation is easy when the desired product is obtained after the completion of the hydrolysis reaction. No effective means has been found as an effective extraction method, and it is necessary to neutralize and extract the acid once or to remove the acid by distillation of the reaction solution under reduced pressure, which is not satisfactory in industrial practice. Similarly, when concentrated sulfuric acid is used, a large amount of acid is required, and when a high-temperature reaction is performed to shorten the reaction time, the target product is decomposed and the yield decreases. Further, in any of the above cases, there is a possibility that alcohol produced as a by-product during the reaction may inhibit the hydrolysis reaction, and a large excess of water must be present in the system to avoid the hydrolysis reaction, which lowers the efficiency of the apparatus. Thus, a hydrolysis reaction effective for industrial implementation is required.

[0004]

Means for Solving the Problems However, the inventors of the present invention have made intensive studies and found that when the acetal is hydrolyzed in the presence of a phosphoric acid catalyst, all of the conventional disadvantages are solved and industrially easy. They have found that acetaldehyde, which is the corresponding target, can be produced, and have completed the present invention.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The reaction of the present invention is represented by the following formula (1).

Embedded image

Here, R is an alkyl group such as methyl, ethyl, propyl, butyl, etc., a phenyl group, and a henzyl group.
Acetals that can be advantageously used in the present invention are benzyloxyacetaldehyde dialkyl acetals, where alkyl is typically methyl, but also includes ethyl, propyl, butyl and the like. Hereinafter, a method for hydrolyzing benzyloxyacetaldehyde dialkyl acetal will be specifically described.

In carrying out the hydrolysis reaction, benzyloxyacetaldehyde dialkyl acetal and phosphoric acid are supplied to a reactor charged with water to carry out the reaction. Benzyloxyacetaldehyde dialkyl acetal is supplied by dissolving it in an organic solvent having no compatibility with water in order to easily obtain a product after the reaction. As the solvent, aromatic hydrocarbons such as benzene, xylene and toluene, and aliphatic and alicyclic hydrocarbons such as pentane, hexane and cyclohexane can be used. Phosphoric acid is usually 85
% Aqueous solution. Such drugs are usually advantageously batch-packed, but may be divided and continuously charged as needed.

The amount of each chemical used is 0.01 to 10 parts by weight, preferably 0.1 to 0.5 parts by weight, of phosphoric acid per 1 part by weight of benzyloxyacetaldehyde dialkyl acetal, and 1 to 5 parts by weight of water. About 10 parts by weight is practical. Benzyloxyacetaldehyde dialkyl acetal is used as an organic solvent solution having a concentration of about 20 to 60% by weight. The reaction temperature may be 70 ° C. or higher, but is preferably 80 to 95 ° C., and the reaction time is 15 ° C.
Time is advantageous.

In the reaction, it is advantageous in terms of yield that the alcohol produced as a by-product is removed to the outside of the system, and the reaction is continued while preferably distilling off the solvent and water. After the completion of the reaction, the reaction product liquid is left to separate into two layers, an organic layer in which the target substance is dissolved and an aqueous layer. Since benzyloxyacetaldehyde is dissolved in the organic layer, the solvent is distilled off to obtain the desired product. Further purification is performed if necessary. The yield of the target compound is about 85 to 95% based on the starting material benzyloxyacetaldehyde dialkyl acetal.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to examples.
“%” Is based on weight. Example 1 Benzyloxyacetaldehyde dimethyl acetal 1
460 g of a toluene solution containing 97.8 g, 989 g of water and 46.5 g of 85% phosphoric acid were charged into a reactor and heated to 85 ° C. The hydrolysis reaction is performed while removing by-product methyl alcohol as an azeotrope with water and toluene.Furthermore, toluene is separated from the distillate and returned to the reaction system, and water is supplied in an amount corresponding to the amount of distillate water. For 15 hours.

After completion of the reaction, the reaction solution was cooled to room temperature and allowed to stand to separate into two layers, and a toluene layer was separated. 139.3 g of benzyloxyacetaldehyde in the toluene layer
(92% yield).

Example 2 The procedure of Example 1 was carried out using benzyloxyacetaldehyde diethyl acetal as a starting material instead of benzyloxyacetaldehyde dimethyl acetal. The yield of benzyloxyacetaldehyde was 91%.

Control Example 1 The same experiment as in Example 1 was carried out except that 9.9 g of concentrated sulfuric acid was used instead of phosphoric acid and the reaction time was changed to 6 hours. As a result, the yield of benzyloxyacetaldehyde was obtained. Was only 78%.

Control Example 2 The same experiment as in Example 1 was carried out except that 890 g of acetic acid was used instead of phosphoric acid and the reaction time was changed to 8 hours. As a result, the yield of benzyloxyacetaldehyde was 65%. It was only.

[0015]

According to the present invention, a phosphoric acid catalyst is used in producing benzyloxyacetaldehyde which is useful as an intermediate of pharmaceuticals such as anti-AIDS by hydrolyzing benzyloxyacetaldehyde dialkyl acetal. As a result, the target product can be obtained industrially easily and in good yield.

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Claims (3)

[Claims] 1. A method for hydrolyzing an acetal, comprising hydrolyzing the acetal in the presence of a phosphoric acid catalyst. 2. A process for hydrolyzing acetal according to claim 1, wherein benzyloxyacetaldehyde dialkyl acetal is used as the acetal. 3. The method for hydrolyzing an acetal according to claim 1, wherein the reaction is carried out while removing by-product alcohol in the reaction system to the outside of the system.