JPS5939842A - Preparation of acetals - Google Patents

Abstract

PURPOSE:To prepare an acetal useful as a preparation raw material of 3-acylsalicylic acid, etc. which is an intermediate of pharmaceuticals, etc., easily, in high yield, by reacting a 2-cyanophenol compound with an alcohol in the presence of an acid catalyst in combination with a dehydration agent. CONSTITUTION:The acetal of formula II (R<2> and R<3> are hydrocarbon group or together form alkylene) is prepared by reacting the 2-acylphenol compound of formula I (R<1> is H or hydrocarbon group) with an alcohol such as 2-6C alkylene glycol (e.g. ethylene glycol) in an inert diluent (preferably benzene, etc.) in the presence of an acid catalyst and a dehydration agent at 30-200 deg.C under arbitrary pressure. The acid catalyst is, e.g. sulfuric acid, p-toluensulfonic acid, metasulfonic acid, boron trifluoride.ether complex, etc., and the dehydration agent is, e.g. methyl orthoformate, ethylene carbonate, HY-type zeolite, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing acetals from 2-acylphenol and alcohol, and relates to a method for producing acetals in high yield by using a dehydrating agent together with an acid catalyst.

5-acylsalicylic acids such as 3-propyl salicylic acid are useful as intermediate raw materials for pharmaceuticals, etc., and the present inventors have developed a method for producing 6-acylsalicylic acid derivatives from 2-acylphenols by converting 2-acylphenols into acetals. We have discovered a method in which the phenolate is reacted with carbon dioxide gas to carboxylate the carbonyl group, and then the acetal is hydrolyzed.

In this method, the acetalization reaction of 2-acylphenol is carried out by reacting alcohol or the like in the presence of an acid catalyst such as sulfuric acid or sulfonic acid. In this case, the reaction is usually carried out with azeotropic dehydration in a solvent such as benzene,
This method cannot be said to provide a sufficiently high yield of acetals.

The present invention provides a method for producing acetals at a higher yield by using a dehydrating agent together with an acid catalyst in a method for producing acetals by reacting alcohol with 2-acylphenol. .

That is, the present invention provides a method of reacting a 2-acylphenol represented by the general formula (wherein R1 represents hydrogen or a hydrocarbon group) with an alcohol to form a compound represented by the general formula (wherein R1 is the same as above, R2 and R3 are In a method for producing acetals represented by (representing a hydrocarbon group, R and R may be linked to form an alkylene group),
The present invention relates to a method for producing acetals, characterized in that the reaction is carried out using a dehydrating agent together with an acid catalyst.

The 2-acylphenol to which the present invention is applied is a compound represented by the above general formula (1), in which R1 c,
Representative examples include hydrogen or linear or branched argyl groups such as methyl, ethyl, n-propyl, and 1so-propyl, cyclic alkyl groups such as cyclohexyl, aryl groups such as phenyl and tolyl, and aralgyl groups such as benzyl. It is a hydrocarbon group that

Examples of the alcohol include alkylene glycols having 2 or more carbon atoms such as ethylene glycol, propylene glycol, neopentyl glycol, and hexylene glycol, and polyhydric alcohols such as glycerin.

The acid catalyst used in the present invention includes mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid; 1) sulfonic acids such as luenesulfonic acid, metasulfonic acid, and trifluoromethanesulfonic acid;
Examples include cation exchange resins and Lewis acids such as boron trifluoride ether complexes.

Dehydrating agents used in the present invention include alkyl orthoformates such as methyl orthoformate, ethyl orthoformate, alkylene carbonates such as ethylene carbonate,
Propylene carbonate, propylene carbonate, various zeolites such as HYu zeolite, molecular sieves 3A, 4A.

The compound is at least one compound selected from phosphorus compounds such as phosphorus pentoxide, phosphorus oxychloride, and phosphorus trichloride, and sulfur compounds such as thionyl chloride.

The reaction of the present invention is carried out by reacting 2-acylphenol and alcohol together with an acid catalyst in the presence of a dehydrating agent.

7)-z+ztD Usage ratio Lt is desirably about 1 to about 10 mol, particularly about 1.1 to about 3 mol, per 1 mol of 2-acylphenol.

The amount of acid catalyst used can be changed as appropriate depending on the type of 2-acylphenol and alcohol, but usually 2-acylphenol and alcohol are used.
It is desirable that the amount is about 0.001 to about 0.2 mol, particularly about o, o i to 0.1 mol, per 1 mol of acylphenol.

The amount of the dehydrating agent to be used is arbitrary, but it is preferably in the range of usually 0.1 to about 10 moles, particularly about 0.3 to about 3 moles, per mole of 2-acylphenol.

These dehydrating agents may be added to the reaction system all at once, or may be added in several portions. When using various zeolites as a dehydrating agent, it is desirable to dehydrate the refluxing water-containing solvent with the dehydrating agent and return it to the reaction system.

The reactions of the present invention may be carried out without an inert diluent, but usually an inert diluent such as hegyzane, heptane,
It is carried out in the coexistence of hydrocarbons such as kerosene, cyclohexane, benzene, toluene, xylene, and halogenated hydrocarbons such as chlorobenzene.

The reaction can be carried out under any pressure. The reaction temperature is usually about 30°C to about 200°C, particularly preferably about 5°C.
0°C to about 150°C.

The acetals obtained by the reaction of the present invention have the general formula (
A compound represented by I), in which R2 and R3
is any hydrocarbon group, and preferred examples include those having a structure in which R2 and R3 are linked to form an alkylene group such as ethylene, propylene, alkyl-substituted ethylene, etc.

After the reaction is complete, acetals can be separated from the reaction mixture by conventional means. Alternatively, the reaction mixture can be subjected to a repeat reaction as it is or after some post-treatment without separating the acetals.

According to the present invention, acetals can be produced in higher yields.

Examples are shown below.

Example 1 2-Propionylphenol 7 was added to a 200ml flask equipped with a stirrer, thermometer, and Dean-3tark apparatus.
．． 51 g (C1.05 mol), ethylene glycol 9.32 g (0.i5 mol), ethylene carbonate 5
．． 29 g (0.06 mol), p-)luenesulfonic acid 0.475 g (5 mol%) and benzene 75 m
4 and heated under reflux for 43 hours. After the reaction mixture was cooled, it was poured into aqueous sodium bicarbonate containing ice to separate the layers, the aqueous layer was extracted with benzene, and the organic layers were combined, washed with water, and dried. As a result of gas chromatography analysis, it was 2-7" ROHI.

The conversion rate of onylphenol was 84%, the yield of ethylene acetal was 83%, and the selectivity was 99%.

Example 2 The reaction was carried out in the same manner as in Example 1 except that the amount of ethylene carbonate in Example 1 was changed to 8.81 g, and the conversion rate was 87%, the yield was 86%, and the selectivity was 99%.

Example 5 Capacity 200ml equipped with stirrer, thermometer, and cooler
In a flask, 2-propionylphenol 7 (0.15 mol), methyl orthoformate 7, 69 g (0.075
When 0.475 g (5 mol %) of p-toluenesulfonic acid and 75 J of benzene were added and heated under reflux for 8 hours, the conversion rate was 97%, the yield was 95%, and the selectivity was 98%.

Examples 4 to 6 Same as Example 3 except that the amount of methyl orthoformate in Example B was changed to the amount shown in Table 1, or ethyl orthoformate was used in the amount shown in Table 1 instead of methyl orthoformate. When the reaction was carried out, the results shown in Table 1 were obtained.

Table 1 Example 7 Instead of heating and refluxing for 48 hours in Example 1, heating was performed for 12 hours.
After azeotropic dehydration, HY type zeolite (product name SK-4
1) Add 5.0 g and continue for 12 h. When the reaction was carried out by heating, the conversion rate was 70%, the yield was 68%, and the selectivity was 9.
It was 7%.

Examples 8 to 9 The reaction was carried out in the same manner as in Example 3, except that the alcohol shown in Table 2 was used in the amount shown in Table 2 instead of the ethylene glycol in Example 6, and the results shown in Table 2 were obtained.

Table 2 Examples 10 to 12 The reaction was carried out in the same manner as in Example 1, except that the acids shown in Table 6 were used in the amounts shown in Table 3 instead of real [IJl p-)luenesulfonic acid, and the results shown in Table 3 were obtained. was gotten.

Table 5 Example 13 The reaction was carried out in the same manner as in Example 1 except that 6.81 g of 2-acetylphenol was used instead of 2-propionylphenol in Example 1. The conversion rate of 2-acetylphenol was as follows. 89%, the yield of ethylene acetal is 88%,
The selectivity was 99%.

Examples 14-15 The reaction was carried out in the same manner as in Example 1, except that the solvent shown in Table 4 was used instead of benzene in Example 1, and the results shown in Table 4 were obtained.

Table 4 Comparative Example 1 When a reaction was carried out in the same manner as in Example 1 without using ethylene carbonate, the conversion rate of 2-propionylphenol was 55% and the yield of ethylene ketal was 55%.
4%, and the selection rate was 98%.Applicant: Mitsui Petrochemical Industries Co., Ltd. Agent Kazu Yamaguchi

Claims (1)

[Claims] (1) 2 represented by the general formula (wherein R represents hydrogen or a hydrocarbon group)
-By reacting acylphenols with alcohol, the general formula (wherein R1 is the same as above, R2 and R3 represent a hydrocarbon group, and R and R may be connected to form an alkylene group) A method for producing acetals represented by the following, characterized in that the reaction is carried out in the presence of a dehydrating agent together with an acid catalyst.