JPH08134013A - Production of 4-alkylbenzonic acids - Google Patents

Abstract

PURPOSE: To industrially and advantageously produce 4-alkylbenzoic acids in high yield and purity according to reaction only in one step by thermally reacting 4-alkylbenzaldoximes in the presence of an acid. CONSTITUTION: 4-Alkylbenzoic acids of formula II are obtained simply by thermally reacting 4-alkylbenzaldoximes of formula I (R is a 1-5C lower alkyl) in the presence of an acid such as sulfuric, hydrochloric or phosphoric acid. The 4-alkylbenzoic acids of formula II themselves are useful as a perfume compound or a synthetic intermediate for perfumes, medicines, agrochemicals, liquid crystal compounds, etc. Furthermore, the 4-alkylbenzoic acids of formula II can readily be converted into 4-alkylbenzoic esters of formula III (R1 is an alkyl or a cycloalkyl) by carrying out the esterifying reaction thereof with alcohols in the presence of an acidic catalyst, e.g. sulfuric acid, hydrochloric acid or an alkylsulfuric acid. The compounds of formula III themselves are useful as a perfume compound or a synthetic intermediate for perfumes, medicines, agrochemicals, liquid crystal compounds, etc.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the following formula (1) useful as a perfume compound per se and as a synthetic intermediate for perfumes, pharmaceuticals, agricultural chemicals, liquid crystal compounds and the like.

[0002]

Embedded image [Wherein R represents a C _{1 to} C ₅ lower alkyl group], and a novel method for producing a 4-alkylbenzoic acid.

[0003]

2. Description of the Related Art Conventionally, alkyl-substituted benzoic acids have been produced by permanganic acid oxidation, chromic acid oxidation, etc. of corresponding aromatic aldehydes. However, the problems such as generation of a large amount of by-products or environmental pollution due to catalysts are involved. , And some alternative reactions have been proposed.

For example, a method of oxidizing cumin aldehyde with hydrogen peroxide under alkaline conditions using an inorganic alkali salt such as sodium hydroxide or potassium hydroxide to obtain cumin acid (JP-A-63-264551), saturation. Alternatively, a method for synthesizing carboxylic acids, which comprises treating an unsaturated alicyclic or aromatic aldehyde with an organic peracid in a basic organic solvent to give a corresponding carboxylic acid (JP-A-3-157345) ) Etc. have been proposed.

On the other hand, as a method for producing alkyl-substituted benzoic acids using alkyl-substituted benzaldoximes as a starting material, for example, alkyl-substituted benzaldoximes are reacted with an acid anhydride such as acetic anhydride to form alkyl-substituted benzonitrile. A method for synthesizing an alkyl-substituted benzoic acid, which is treated with an acid or an alkali after the derivative is introduced, has been proposed.

[0006]

However, the reaction using hydrogen peroxide and an inorganic alkali salt is dangerous and cannot be said to be an industrial method. Also, the oxidation reaction with peracetic acid in a basic organic solvent does not pose a problem in the reaction itself, but since the method of adding a large amount of water to precipitate the product after the reaction is adopted, the reaction is not performed. It is difficult to recover the water-miscible basic organic solvent used, and there is a problem to be solved in terms of manufacturing cost.

Further, in the method using an alkyl-substituted benzaldoxime as a starting material, it is necessary to isolate the generated alkyl-substituted benzonitrile, so that it takes a long time to carry out the treatment after the reaction, and the industrial production method As a result, it has disadvantages.

[0008]

DISCLOSURE OF THE INVENTION The inventors of the present invention have earnestly studied a method for producing an industrially advantageous 4-alkylbenzoic acid compound which can solve the above-mentioned problems of the prior art. as a result,
Formula (2) below

[0009]

[Chemical 4] [Wherein R represents a C _{1 to} C ₅ lower alkyl group], and a 4-alkylbenzaldoxime represented by the formula (1) is reacted by heating in the presence of an acid. The present invention has been completed by discovering that alkylbenzoic acids can be obtained.

Therefore, the object of the present invention is to provide a process for producing a compound of formula (1) in high purity and high yield from the compound of formula (2) under industrially advantageous reaction conditions of only one step. It is in. If the production method of the present invention is shown in a reaction process diagram, it can be represented as follows, for example.

[0011]

Embedded image [In the formula, R represents a C _{1 to} C ₅ lower alkyl group,]

The 4-alkylbenzaldoximes used as a raw material in the present invention can be easily obtained on the market. Also, for example, 4-methylbenzaldehyde,
4-ethylbenzaldehyde, 4-isopropylbenzaldehyde, 4-t-butylbenzaldehyde and the like 4-
It can also be easily synthesized by a conventionally known method in which an alkylbenzaldehyde is reacted with sulfuric acid or hydroxylamine hydrochloride in the presence of an alkali.

According to the present invention, the 4-alkylbenzaldoxime of the formula (2) is reacted by heating in the presence of an acid to industrially advantageously produce the 4-alkylbenzoic acid of the formula (1). It can be produced in high yield and high purity.

The heating conditions for the above reaction are, for example, about 50 ° C.
About 200 ° C, more preferably about 80 ° C to about 150 ° C
Is preferably selected. The reaction time is about 1 hour to about 8 hours.

Specific examples of the alkyl group of the 4-alkylbenzaldoxime of the formula (2) used in this reaction include groups such as methyl, ethyl, isopropyl, propyl, isobutyl, butyl, isopentyl and pentyl. It is preferably exemplified.

Examples of the type of acid used in the reaction include inorganic acids such as sulfuric acid, hydrochloric acid and phosphoric acid. Further, these inorganic acids are preferably used in the form of an aqueous solution, and for example, an inorganic acid aqueous solution having an acid aqueous solution concentration of 30% or more, more preferably 50% or more is used. The amount of the acid used is about 1 to about 10 with respect to 1 mol of the compound of the formula (2).
Amounts on the order of moles are preferred.

Furthermore, this reaction is usually preferably carried out in the absence of an organic solvent, but it can also be carried out in the presence of an organic solvent. Specific examples of the organic solvent in this case include, for example, benzene, toluene, xylene, hexane, cyclohexane, octane, decane, and the like, and the amount thereof is not particularly limited and can be arbitrarily selected. A range of about 0.5 to about 10 parts by weight is often employed for 1 part by weight of the 4-alkylbenzaldoxime of the formula (2).

After completion of the reaction, the reaction product is represented by the formula (1) in high yield and high purity by appropriately adopting ordinary separation means such as distillation, washing, extraction, crystallization, drying and column chromatography. The 4-alkylbenzoic acids can be obtained. Specific preferred examples of the compound of formula (1) thus obtained include 4-methylbenzoic acid and 4-
Ethylbenzoic acid, 4-isopropylbenzoic acid, 4-propylbenzoic acid, 4-butylbenzoic acid, 4-isobutylbenzoic acid, 4-pentylbenzoic acid, 4- (3-methylbutyl) benzoic acid and the like are exemplified.

Further, the equation (1) obtained as described above
4-alkylbenzoic acids of formula ( ₁ ) can be easily prepared by a conventionally known method, for example, by subjecting the acid to an esterification reaction with alcohols (R ₁ OH) in the presence of an acidic catalyst such as sulfuric acid, hydrochloric acid or alkyl sulfuric acid, 3)

[0020]

[Chemical 6] [Wherein R ₁ represents a C _{1 to} C ₅ alkyl group, a C _{5 to} C ₆ cycloalkyl group, and R represents a C _{1 to} C ₅ lower alkyl group]. It can be induced to benzoic acid esters. Specific examples of the alkyl group of the esters include methyl, ethyl, propyl, butyl, etc.
Specific examples of the cycloalkylalkyl group include cyclopentyl and cyclohexyl.

The 4-alkylbenzoic acid esters of the formula (3) can also be used as a perfume compound in the same manner as the 4-alkylbenzoic acids of the formula (1), as well as perfumes, pharmaceuticals, agricultural chemicals,
It is useful as a synthetic intermediate for liquid crystal compounds and the like.

Hereinafter, the embodiments of the present invention will be described more specifically with reference to Examples.

[0023]

【Example】

Example 1 Preparation of 4-isopropylbenzoic acid [compound of formula (1)]. 212 g of 80% sulfuric acid aqueous solution in a 2 liter reaction flask
And heated to 115 ° C. To this, a solution of 187 g (1.1 mol) of 4-isopropylbenzaldehyde oxime and 85 g of xylene is added dropwise over about 2 hours under the temperature condition of 120 ° C to 125 ° C. About 1 at the same temperature after dropping
After stirring for an hour, further heat to 125 ℃ ~ 139 ℃,
Xylene was recovered. The reaction solution was cooled to 90 ° C, and water (1
000 g) is added and the mixture is stirred at the same temperature for 30 minutes and cooled. The formed crystals were filtered, washed thoroughly and then recrystallized from methanol (200 ml) to give 153 g of pure 4-isopropylbenzoic acid having a melting point of 117 ° C. (yield: 85
%) Was obtained.

Example 2 Preparation of 4-ethylbenzoic acid [compound of formula (1)] According to the method of Example 1, 80% sulfuric acid aqueous solution (21.2
1) g of 4-ethylhenzaldehyde oxime
(0.11 mol) was added, and the mixture was heated and reacted at 120 ° C. for 4 hours, and then treated in the same manner as in Example 1 and had a melting point of 112 ° C.
13.5 g of pure 4-ethylbenzoic acid (yield: 79
%) Was obtained.

Examples 3 to 8 Various compounds of formula (1) were produced according to the production method of Example 1 or Example 2. The results are shown below.

No Formula (2) Type of Compound Acid (Aqueous Solution ) Formula (1) Compound Yield (%) 3 4-Methylbenzaldoxime 80% 4-Methylbenzoic Acid Sulfate 75 4 4-Propylbenzaldoxime 80% Sulfuric acid 4-fluorobenzoic acid 86 5 4-Butyl benzaldoxime 80% Sulfuric acid 4-butyl benzoic acid 90 6 4-Isobutyl benzyl aldoxime 90% Sulfuric acid 4-isobutyl benzoic acid 86 7 4-Pentyl benzaldoxime 80% Sulfuric acid 4 -Pentylbenzoic acid 90 8 4- (3-Methylbutyl) benzaldoxime 80% Sulfuric acid 4- (3-Methylbutyl) benzoic acid 82

Reference Example 1 Production of ethyl 4-isopropylbenzoate [compound of formula (3)]. A 2-liter reaction flask was charged with 150 g (0.89 mol) of 4-isopropylbenzoic acid synthesized in Example 1, and ethyl alcohol (150 g) was added. Concentrated sulfuric acid 4
After dropping 5 g and heating for 2 hours, ethanol is recovered under normal pressure. Extracted with toluene (100 g), washed, and crude product 1
70 g were obtained. This was purified to obtain 161 g of pure ethyl 4-isopropylbenzoate (yield: 94%).

[0028]

INDUSTRIAL APPLICABILITY According to the present invention, 4-alkylbenzaldoximes are heated and reacted in the presence of an acid to give the desired 4-alkylbenzoic acids in a high yield and a high purity in only one step reaction. An industrially advantageous manufacturing method that can be used for manufacturing is provided.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Hiroyuki Watanabe Inventor Hiroyuki Watanabe 335 Kayajuku Nakagawa-ku, Kanagawa Prefecture Hasegawa Kaori Co., Ltd.Technical Research Institute Inside the technical laboratory

Claims (1)

[Claims] 1. The following formula (2): [Wherein R represents a C _{1 to} C ₅ lower alkyl group], and a 4-alkylbenzaldoxime compound represented by the following formula (1) is reacted under heating in the presence of an acid. Chemical 2] [Wherein R represents a C _{1 to} C ₅ lower alkyl group], and a method for producing a 4-alkylbenzoic acid.