JPH11228488A - Production of cinnamic acids - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing cinnamic acids useful as an intermediate for an agrochemical, a medicine and a perfume by heating benzylidene diacetates in the presence of a basic catalyst. SOLUTION: Benzylidene diacetates e.g. a compound of formula I [X is H, a halogen, an alkoxy, hydroxyl, an acyloxy, nitro or the like; (n) is 1-5]} is heated in the presence of a basic catalyst (e.g. sodium acetate and potassium acetate) to provide the objective cinnamic acids in the method for producing the cinnamic acids. The reaction liquid after forming benzylidene diacetates by acetoxylating an aromatic compound of formula II in acetic anhydride can be used as the reaction raw material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing cinnamic acids by reacting benzylidene diacetates in the presence of a basic catalyst. Cinnamic acids are compounds useful as intermediates for pesticides, medicines and fragrances.

[0002]

2. Description of the Related Art Conventional cinnamic acid synthesis methods are described in (1) Journal of American Chemical Society (Journal).
of Chemical Society) Vol. 79, pp. 220 (1957),
U.S. Pat. No. 3,470,151 discloses a Perkin reaction for reacting benzenes with human acetic anhydride in the coexistence of sodium acetate, and (2) Journal of American Chemical Society.
ciety) 69, 852 pages (1947), USP 3,470,151
Disclose a Knoevenagel condensation reaction in which malonic acid is reacted with an organic base such as pyridine.

[0003]

Problems to be Solved by the Invention (1) and (2)
In the above method, the yield of cinnamic acids was not sufficient, and an excess of acetic anhydride or malonic acid with respect to the substrate was required to improve the yield. In addition, in the case of (2), there is a drawback that expensive malonic acid is used, which is not preferable as an industrial production method of cinnamic acids. In addition, the starting materials, benzaldehydes, are relatively unstable,
When left in the air, it was gradually oxidized and converted to benzoic acids, which made handling difficult.

An object of the present invention is to provide a method for producing cinnamic acids which is industrially applicable and economically advantageous.

[0005]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, as a novel method for producing cinnamic acids, using benzylidene diacetates as a raw material, the corresponding cinnamic acid in high yield was obtained. The inventors have found that acids are generated, and have reached the present invention. That is, the present invention is a method for producing cinnamic acids, which comprises reacting benzylidene diacetates by heating them in the presence of a basic catalyst.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The basic catalyst in the present invention may be either an organic basic compound or an inorganic basic compound. The fact that the compound has basicity is immersed in pH test paper,
It is easily confirmed by a method such as measuring with a pH meter after preparing an aqueous solution, observing discoloration of color using an indicator, or measuring adsorption of carbon dioxide gas. Specific examples of the organic base compound include organic amines such as pyridine, pyrrolidine, methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, tetraethylammonium hydroxide, tetramethylammonium hydroxide, aniline, and toluidine. Examples of the inorganic base compound include salts of a strong base and a weak acid, such as an alkali metal acetate, an alkali metal propionate, and an alkali metal carbonate.

The amount of the basic catalyst used varies depending on the reaction substrate and the reaction conditions, but is preferably 0.01 to 5 mol times, more preferably 0.2 to 1 mol times, relative to the benzylidene diacetates. It is.

[0008] The benzylidene diacetates used in the present invention are not particularly limited. For example, general formula (1)

Embedded image (Wherein X is a hydrogen atom, a halogen group, an alkoxy group, a hydroxyl group, an acyloxy group, a nitro group, an allyl group, an alkyl group, an aryl group, a cyano group, an amino group, an amide group,
It represents at least one selected from an acyl group, a carboxyl group, a formyl group, and a hydroxymethyl group. n = 1 ~
The example represented by 5) is exemplified. Here, the alkoxy group, the alkyl group, and the amide group each have 1 to 6 carbon atoms.
The acyloxy group, allyl group and acyl group each preferably have 2 to 6 carbon atoms, and the aryl group preferably has 6 to 12 carbon atoms. More preferably benzylidene diacetate, chlorobenzylidene diacetate, dichlorobenzylidene diacetate,
Nitrobenzylidene diacetate, methoxybenzylidene diacetate, hydroxybenzylidene diacetate, acetoxybenzylidene diacetate, and phenoxybenzylidene diacetate.

The benzylidene diacetate used in the present invention may be a pure substance itself or may contain it. For example, a reaction solution after acetoxylation of a methyl group-substituted aromatic compound in acetic acid and / or acetic anhydride to produce benzylidene diacetates may be used as a reaction raw material of the present invention.

When a methyl-substituted aromatic compound is acetoxylated in acetic anhydride and then reacted in the presence of a basic catalyst, the methyl-substituted aromatic compound used in the present invention includes: Although not particularly limited, for example, general formula (2)

Embedded image (Wherein X is a hydrogen atom, a halogen group, an alkoxy group, a hydroxyl group, an acyloxy group, a nitro group, an allyl group, an alkyl group, an aryl group, a cyano group, an amino group, an amide group,
It represents at least one selected from an acyl group, a carboxyl group, a formyl group, and a hydroxymethyl group. n = 1 ~
The example represented by 5) is exemplified. Here, the alkoxy group, the alkyl group, and the amide group each have 1 to 6 carbon atoms.
The acyloxy group, allyl group and acyl group each preferably have 2 to 6 carbon atoms, and the aryl group preferably has 6 to 12 carbon atoms. More preferred are toluene, xylene, chlorotoluene, dichlorotoluene, nitrotoluene, methoxytoluene, phenoxytoluene, cresol and methylbenzyl alcohol.

Although the present invention is carried out only with benzylidene diacetate and a basic catalyst, acetic anhydride may coexist in the reaction system. Acetic anhydride has the effect of accelerating the reaction and improves the yield of cinnamic acids. The amount of acetic anhydride to be coexisted varies depending on the reaction substrate and reaction conditions, but is 0.01 to 0.01% relative to benzylidene diacetates.
10 mole times is preferable, and more preferably 0.1 to 5 times.
It is a molar amount. If the amount of acetic anhydride to coexist is too small, the present effect is small, while if the amount is too large, although the effect is recognized, it is necessary to recover unreacted acetic anhydride, etc. Become.

In the present invention, an appropriate solvent can be used. Suitable solvents include benzylidene diacetate used under the reaction conditions and those inert to organic alkali salts, such as acetic acid, hexane, cyclohexane, petroleum ether, diethyl ether, tetrahydrofuran, nitrobenzene, chlorobenzene, dichlorobenzene and Trichlorobenzene and the like. The amount of the solvent used is usually 1 to 10 times the total amount of benzylidene diacetate to be reacted.

[0013] The reaction temperature in the present invention is appropriately selected depending on the reaction substrate and reaction conditions, but is usually 100 to 3.
00 ° C, preferably 120 to 250 ° C. At this time, the reaction time is usually 0.5 to 24 hours, preferably 1 to 12 hours in the case of batch operation or semi-batch operation.

The reaction pressure is not particularly limited.
Whether the reaction is performed at normal pressure or under pressure is appropriately selected depending on the reaction substrate and the like.

After completion of the reaction, the formed cinnamic acids are separated from the reaction system by extracting with an alkaline aqueous solution, and the extracted solution is neutralized or acidified by adding an acid to isolate the cinnamic acids. can do. When unreacted raw materials are recovered, they can be used again for the reaction.

As described above, according to the present invention, cinnamic acids can be obtained in high yield by heating and reacting benzylidene diacetates in the presence of a basic catalyst. This is extremely advantageous as a typical production method.

[0017]

Hereinafter, the present invention will be described with reference to examples.
The present invention is not limited to these Examples.

The basic catalyst used was primary sodium acetate and potassium acetate manufactured by Katayama Chemical, and m-chlorobenzaldehyde manufactured by Wako Pure Chemical and primary acetic anhydride manufactured by Kanto Chemical were used as raw materials for synthesizing benzylidene diacetate. .

(Synthesis of m-chlorobenzylidene diacetate) 112.5 g of m-chlorobenzaldehyde and 163.2 g of acetic anhydride were put into a three-necked flask, and stirred in a water bath at 20 ° C., while the H-form manufactured by PQ was added. 3.5 g of β-zeolite was charged and stirred for 20 hours. After the reaction solution was filtered to separate the catalyst, 200 g of water and 100 g of ethyl acetate were added to the mother liquor, and an oil phase was obtained by liquid separation. After the ethyl acetate was distilled off by an evaporator, n-hexane was added to the residue.
0 g was added and left. After standing at room temperature overnight, the precipitate was filtered, sufficiently washed with n-hexane, and vacuum dried at 60 ° C. for 8 hours to obtain m-chlorobenzylidene diacetate crystals.

[0020]

Example 1 m-chlorobenzylidene diacetate 2
4.26 g and 6.15 g of sodium acetate were put into a three-necked flask and refluxed in a 200 ° C. oil bath for 9 hours. After cooling, 100 g of ethyl acetate was added, a saturated aqueous solution of sodium hydrogen carbonate was further added, and the mixture was sufficiently stirred to extract m-chlorocinnamic acid into an aqueous phase.
After separating the aqueous phase, hydrochloric acid was added until pH = 2, and the precipitated m-chlorocinnamic acid was filtered. Next, washing with water was sufficiently performed, and vacuum drying was performed at 60 ° C. for 8 hours. After drying, it was weighed. The purity of the obtained product was analyzed by high performance liquid chromatography. The yield of m-chlorocinnamic acid and the conversion of m-chlorobenzylidene diacetate were determined by the following equations.

[0021]

(Equation 1) Table 1 shows the reaction results.

[0022]

Example 2 The same operation as in Example 1 was performed except that 7.36 g of potassium acetate was used instead of 6.15 g of sodium acetate. Table 1 shows the reaction results.

[0023]

Example 3 m-chlorobenzylidene diacetate 2
The same operation as in Example 1 was performed, except that 2.55 g of acetic anhydride was further added to 4.26 g and 6.15 g of sodium acetate. Table 1 shows the reaction results.

[0024]

Example 4 The same operation as in Example 1 was carried out except that 5.30 g of sodium acetate was used instead of 6.15 g of sodium acetate.

[0025]

[Table 1]

From the above results, it was found that heating benzylidene diacetates in the presence of a basic catalyst can produce the corresponding cinnamic acids in high yield.

[0027]

According to the present invention, in the presence of a basic catalyst,
By heating and reacting benzylidene diacetates, cinnamic acids can be produced in high yield.

Claims (7)

[Claims] 1. A method for producing cinnamic acids which is reacted by heating benzylidene diacetates in the presence of a basic catalyst. 2. A benzylidene diacetate represented by the general formula (1): ## STR1 ## (Wherein X is a hydrogen atom, a halogen group, an alkoxy group, a hydroxyl group, an acyloxy group, a nitro group, an allyl group, an alkyl group, an aryl group, a cyano group, an amino group, an amide group,
It represents at least one selected from an acyl group, a carboxyl group, a formyl group, and a hydroxymethyl group. n = 1 ~
The method for producing cinnamic acids according to claim 1, wherein the method is represented by 5). 3. The method for producing cinnamic acids according to claim 1, wherein the basic catalyst is an alkali metal compound. 4. The method for producing cinnamic acids according to claim 3, wherein the alkali metal compound is at least one selected from a sodium compound and a potassium compound. 5. The method for producing cinnamic acids according to claim 1, wherein the benzylidene diacetate is heated at a reaction temperature of 100 ° C. or higher. 6. The method for producing cinnamic acids according to claim 1, wherein acetic anhydride is allowed to coexist in the reaction system when producing cinnamic acids from benzylidene diacetate. 7. A method according to claim 1, wherein the methyl-substituted aromatic compound is acetic acid and / or
Or producing a benzylidene diacetate by acetoxylation in acetic anhydride, followed by a reaction in the presence of a basic catalyst, to produce cinnamic acids according to any one of claims 1 to 6. Method.