JPH05186454A - Production of coumarin and its derivative - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate for perfumes, agricultural chemicals, pharmaceuticals and dyes in high yield by cyclizing and dehydrogenating a propionic acid ester under specific condition. CONSTITUTION:A 3-(2-cyclohexanoyl)propionic acid ester of formula I (R1 to R4 are H, methyl or ethyl provided that at least two of R1 to R4 are H; R5 is 1-4C alkyl) is subjected to cyclization and dehydrogenation reaction in the presence of a Pd catalyst to obtain the compound of formula II. The former half of the reaction is carried out at 230-260 deg.C under a stirring power of 0.05-0.5kW/m<3> and the latter half of the reaction is performed by raising the reaction temperature from that of the former half reaction by 20-40 deg.C and increasing the stirring power by 1-1.5kW/m<3>. The conversion of the starting compound of formula I can be increased to solve the problem of ill odor caused by the contamination of the product with the starting raw material.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an improvement in a process for producing coumarin and its derivatives from 3- (2-cyclohexanoyl) propionic acid esters. Similar to 3,4-dihydrocoumarins, coumarin and its derivatives are important compounds particularly in the perfumery industry, and are also important compounds that can be intermediates for agricultural chemicals, drugs or dyes.

[0002]

2. Description of the Related Art As a conventional method for obtaining coumarin and its derivatives, cyclization dehydrogenation is performed by heating 3- (2-cyclohexanoyl) propionic acid esters in the presence of a hydrogenation-dehydrogenation catalyst such as palladium. (U.S. Pat. No. 3,442,910), a method of cyclizing and dehydrogenating coexisting with a noble metal catalyst such as palladium and co-catalyst barium sulfate, nickel oxide, etc. -181082) and the like are known.

[0003]

However, the yields of coumarin and its derivatives are not always high in the conventional methods. Further, when the reaction is performed under severe conditions in the initial stage of the reaction, the conversion rate of the starting material 3- (2-cyclohexanoyl) propionic acid ester becomes poor. This 3- (2
If a small amount of -cyclohexanoyl) propionic acid ester remains, it is difficult to remove it even after purification, so that it may be mixed into the product and cause an offensive odor as an impurity.

As a result of intensive studies on the production method of coumarin and its derivatives with high yield and economical efficiency, the present inventors conducted the reaction in the first half of the reaction at a relatively low temperature and low stirring power, and in the latter half of the reaction. It was found that by increasing the temperature and / or the stirring power, the yield of coumarin and its derivatives was significantly improved, and the conversion rate of 3- (2-cyclohexanoyl) propionic acid ester as a raw material was improved. The present invention has been completed.

[0005]

That is, the present invention is based on the general formula (1),

[Chemical 3] (In the formula, R _{1 to} R ₄ each represent a hydrogen atom, a methyl group or an ethyl group, and at least two groups of R _{1 to} R ₄ are hydrogen atoms. R ₅ is an alkyl group having 1 to 4 carbon atoms. 3- (2-cyclohexanoyl) represented by
Propionates are cyclized and dehydrogenated in the presence of a palladium catalyst by the general formula (2),

[Chemical 4] (In the formula, R _{1 to} R ₄ are the same as the groups described above.) In producing coumarin and its derivatives, the conversion rate of 3- (2-cyclohexanoyl) propionic acid ester as a raw material In the latter half of the reaction, the reaction temperature is raised more than in the first half of the reaction, and the coumarin and its derivatives are produced.

Examples of 3- (2-cyclohexanoyl) propionic acid esters used in the present invention include:
Methyl 3- (2-cyclohexanoyl) propionate,
Butyl 3- (2-cyclohexanoyl) propionate,
Methyl 3- (2-cyclohexanoyl-3-methyl) propionate, Methyl 3- (2-cyclohexanoyl-5-methyl) propionate, Propyl 3- (2-cyclohexanoyl-4-ethyl) propionate , Propyl 3- (2-cyclohexanoyl-3,4-diethyl) propionate, propyl 3- (2-cyclohexanoyl-3,4-dimethyl) propionate, 3- (2-cyclohexanoyl-3, 5-Diethyl) methyl propionate, 3-
(2-Cyclohexanoyl-3-ethyl-6-methyl)
Examples include, but are not limited to, methyl propionate and the like.

The catalyst used in the present invention is palladium selected from the group consisting of elements or compounds of Group IIA, IIIA, IVA or VIA of the Periodic Table, such as carbon, alumina, silica gel, barium sulfate and the like. It is a solid metal catalyst supported on at least one carrier. These catalysts can be prepared by known methods, such as the impregnation-support method (“catalyst preparation chemistry”).
It can be obtained by a method of impregnating a carrier with a metal and then reducing the hydrogen with hydrogen at a high temperature (edited by Kaoru Ozaki, published by Kodansha), but a commercially available product may be used as it is.

When the amount of the catalyst used is small, the reaction activity is remarkably low. On the contrary, when the amount of the catalyst is large, the reaction activity is too high, a large amount of by-products are produced, and the cost is high. Therefore, 3- (2-cyclohexanoyl) propion is used. The acid ester is generally used in an amount of about 0.1-5% by weight, preferably about 0.3-2% by weight.

In the latter half of the reaction, the conversion rate of the starting material 3- (2-cyclohexanoyl) propionic acid ester is about 80%.
It is after the above, and it is after about 7 to 15 hours have elapsed after the start of the reaction, although it varies with time depending on the reaction temperature and the like. In the latter half of the reaction, the reaction temperature is raised from the first half of the reaction.

The cyclodehydrogenation reaction of 3- (2-cyclohexanoyl) propionic acid esters is carried out at a reaction temperature of about 100 to 350 ° C, preferably about 230 to 295 ° C. Raw material 3- (2-cyclohexanoyl)
In order to sufficiently react the propionic acid esters and improve the conversion rate, in the first half of the reaction, about 230 to 260 ° C.
Good to do in. Then, in order to improve the yield of coumarin and its derivative, in the latter half of the reaction, about 20-40
It is better to raise the temperature by ℃. If the reaction is carried out at a high temperature from the first half of the reaction, the conversion rate is rather insufficient, which is not preferable.

Regarding the stirring during the reaction, if it is too small,
If the yield of marine is low, and if it is too high, the conversion rate will
The stirring power is about 0.01 to 3kW.
/ M ³, Preferably about 0.05-1.5 kW / m³Line
Be seen. From the first half of the reaction, 1-3 kW / m³Large stirring motion
The reaction may be carried out by stirring with force, but the starting material is 3- (2
-Cyclohexanoyl) propionate
In order to react and improve the conversion rate, the odor should be added in the first half of the reaction.
And stirring power is about 0.05-0.5 kW / m³Stir with
And then improve the yield of coumarin and its derivatives
In the latter half of the reaction, the stirring power is set to about 1 to 1.5.
kW / m³A method of increasing the temperature is preferable.

This cyclization dehydrogenation reaction can also be carried out using a solvent. Examples of the solvent include phenyl ether, benzyl ether, methyl-α-naphthyl ether, ethylnaphthalene, dimethylbiphenyl, dodecane, tetradecane, tetralin, acetophenone, phenylpropylketone, methyl benzoate, dimethyl glutamate and the like.

The cyclization dehydrogenation reaction is carried out by charging 3- (2-cyclohexanoyl) propionic acid ester and a catalyst, and if necessary heating with a solvent at a predetermined temperature for several hours to several tens of hours. As a result of the reaction, 3,4-dihydrocoumarins are obtained at a yield of about 30 to 45% and coumarins at a yield of about 20 to 40%. In addition, orthoethylphenol, dihydrocinnamic acid ester, octahydrocoumarin and the like are by-produced. The reaction solution is washed with alkali if necessary, and coumarin and its derivative are obtained by rectification. 3,4-Dihydrocoumarin is converted to coumarin as a product or by dehydrogenation.

If the conversion rate of 3- (2-cyclohexanoyl) propionic acid ester is poor and it remains, it is difficult to remove it even after purification.
Particularly, when 3,4-dihydrocoumarins are taken out as a product, they are mixed into the product and cause an offensive odor as an impurity.
Therefore, the conversion rate of 3- (2-cyclohexanoyl) propionic acid esters is about 99.5% or more, preferably 9% or more.
9.9% or more, and more preferably 99.95% or more. This can be achieved by the method of the present invention.

[0015]

INDUSTRIAL APPLICABILITY According to the method of the present invention, it is possible to increase the yield of coumarin and its derivatives and to increase the conversion rate of the starting material 3- (2-cyclohexanoyl) propionic acid esters. Therefore, it is possible to solve the problem of offensive odor caused by mixing in the product.

[0016]

EXAMPLES Examples will be given below to specifically explain the present invention, but the present invention is not limited to these examples.

Example 1 Methyl 3- (2-cyclohexanoyl) propionate 3
Catalyst containing 5% by weight of palladium on 00g and activated carbon
(50% water content product) 2.1g 1L 4 mouth
Mix with Rasco, under nitrogen atmosphere, temperature 250 ℃, stirring power
0.11kW / m ³Stir at and heat for 10 hours. That
Then, the temperature was raised to 270 ° C. over 1 hour. Temperature
270 ° C, stirring power 1.3 kW / m³While stirring with
Heated for 15 hours.

After completion of the reaction, the catalyst was filtered from the reaction mixture and analyzed by gas chromatography.
The conversion rate of methyl (2-cyclohexanoyl) propionate is 99.98%, and the yields of coumarin and 3,4-dihydrocoumarin are 3- (2-cyclohexanoyl).
31.0% and 3 respectively for methyl propionate
It was 9.2%.

Example 2 Example 1 was repeated except that the catalyst was washed with water and used.
The conversion rate of methyl 3- (2-cyclohexanoyl) propionate is 100.00%, and coumarin and 3,4-
The yields of dihydrocoumarin were 36.2% and 36.8% based on methyl 3- (2-cyclohexanoyl) propionate, respectively.

Example 3 Methyl 6- (2-cyclohexanoyl) propionate 6
00 g and 4.2 g of a catalyst having 5% by weight of palladium supported on activated carbon were mixed in a 1-liter four-necked flask and stirred under a nitrogen atmosphere at a stirring power of 0.11 kW / m ³ at a temperature of 2
Heated at 50 ° C. for 10 hours. Then, the temperature was raised to 270 ° C. over 1 hour. The mixture was stirred with a stirring power of 0.11 kW / m ³ and heated at a temperature of 270 ° C. for 15 hours.

After the reaction was completed, the catalyst was filtered from the reaction mixture and analyzed by gas chromatography.
The conversion rate of methyl (2-cyclohexanoyl) propionate was 99.97%, and the yields of coumarin and 3,4-dihydrocoumarin were 3- (2-cyclohexanoyl).
23.6% and 4 respectively for methyl propionate
It was 1.4%.

Comparative Example 1 Methyl 3- (2-cyclohexanoyl) propionate 3
00 g and 2.1 g of a catalyst supporting 5% by weight of palladium on activated carbon were mixed in a 1-liter four-necked flask, and the temperature was 240 ° C. and the stirring power was 0.11 kW / m ³ under a nitrogen atmosphere.
Stirred at and heated for 26 hours.

After completion of the reaction, the catalyst was filtered from the reaction mixture and analyzed by gas chromatography.
The conversion rate of methyl (2-cyclohexanoyl) propionate was 99.87%, and the yields of coumarin and 3,4-dihydrocoumarin were 3- (2-cyclohexanoyl).
9.1% and 58.Methyl propionate respectively.
It was 5%.

Comparative Example 2 The same procedure as in Comparative Example 1 was repeated except that the temperature and stirring power were changed as shown in Table 1, and the temperature and stirring power were kept constant during the reaction.
The results are shown in Table 1.

[0025]

[Table 1]

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Kensaku Okusen 5-1 Sokai-cho, Niihama-shi, Ehime Sumitomo Chemical Co., Ltd.

Claims (5)

[Claims] 1. A compound represented by the general formula (1): (In the formula, R _{1 to} R ₄ each represent a hydrogen atom, a methyl group or an ethyl group, and at least two groups of R _{1 to} R ₄ are hydrogen atoms. R ₅ is an alkyl group having 1 to 4 carbon atoms. 3- (2-cyclohexanoyl) represented by
Cyclization and dehydrogenation of propionic acid esters in the presence of a palladium catalyst give a compound of the general formula (2): (In the formula, R _{1 to} R ₄ are the same as the above-mentioned groups.) In producing the coumarin and its derivatives, in the latter half of the reaction, the reaction temperature is raised from the first half of the reaction to react. A method for producing coumarin and its derivatives. 2. The reaction temperature in the first half of the reaction is 230 to 260 ° C.
Then, in the latter half of the reaction, the reaction temperature is set to 20 to 4 from the first half of the reaction.
The method for producing coumarin and a derivative thereof according to claim 1, wherein the temperature is increased by 0 ° C. 3. In the first half of the reaction, the reaction temperature is 230 to
260 ℃, the reaction temperature in the latter half of the reaction from the first half of the reaction to 2
Raise the temperature by 0-40 ° C and stir power 1- through the second half before and after the reaction.
The method for producing coumarin and a derivative thereof according to claim 1, wherein the reaction is carried out by stirring at ³ kW / m ³ . 4. The reaction temperature in the first half of the reaction is 230 to
260 ° C., stirring power is 0.05 to 0.5 kW / m ³ , and reaction temperature is 20 to 4 from the first half of the reaction in the latter half of the reaction.
The method for producing coumarin and a derivative thereof according to claim 1, wherein the stirring power is increased by 1 to 1.5 kW / m ³ at 0 ° C. and the reaction is carried out by stirring. 5. The starting material, 3- (2-cyclohexanoyl)
The method for producing coumarin and a derivative thereof according to claim 1, claim 2, claim 3 or claim 4, wherein the latter half of the reaction is performed after the conversion of the propionate becomes 80% or more.