JP2844178B2 - Method for producing α, β-unsaturated carboxylic acid ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to an .alpha., .Beta. Industrially useful as a synthetic intermediate, a pharmaceutical raw material, a resin raw material, etc., starting from a .beta.-hydroxycarboxylic acid ester.
A process for industrially producing unsaturated carboxylic esters.

[0002]

2. Description of the Related Art Conventionally, as a method of synthesizing an unsaturated compound by an elimination reaction of alcohols, a method using an acid catalyst such as sulfuric acid, phosphoric acid, oxalic acid, a method using a solid catalyst such as alumina, silica gel, montmorillonite and the like are known. , FeS
A method using a metal catalyst such as O ₄ , CuSO ₄ , and NiSO ₄ is known (for example, New Experimental Chemistry Course, Vol. 14, p.
119). However, under the reaction conditions using these catalysts, high temperatures are required, and when attempting to carry out the reaction using β-hydroxycarboxylic acid ester, decomposition, polymerization reaction and the like occur, and a satisfactory yield cannot be obtained. Also, β-
In the case of the elimination reaction from the hydroxycarboxylic acid ester,
As a product, two kinds of isomers of an α, β-unsaturated carboxylic acid ester and a β, γ-unsaturated carboxylic acid ester can be produced. In the case of a reaction using these catalysts, a mixture of isomers is obtained. The selectivity of the desired α, β-unsaturated carboxylic acid ester obtained is generally not high.

[0003]

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In the case of a raw material having an electron-withdrawing group at the β-position of a hydroxyl group such as a β-hydroxycarboxylic acid ester, the elimination reaction proceeds even using a strong base catalyst such as KOH or NaOMe. (J.
Am. Chem. Soc., 70 , 1895 (1948), J. Am. Chem. So
c., 81 , 2822 (1959)). In this case, the formation of regioisomers as described above is suppressed, and the selectivity of the target α, β-unsaturated compound is increased. In such a case, a carboxylic acid is generated by a hydrolysis reaction of the raw material and the product, and the desired α, β-unsaturated carboxylic acid ester can be obtained only in a low yield. Therefore, as a method for preventing these side reactions, POCl ₃ , SOCl ₂ ,
A method of converting a hydroxyl group into a suitable reactive group using a halogenating agent such as MeSO ₃ Cl, pTsCl, or the like, a sulfonating agent, or the like, and then performing elimination under mild conditions is performed.
(J. Am. Chem. Soc., 75 , 4830 (1953), J. Am. Chem.
Soc., 77 , 1028 (1955), J. Am. Chem. Soc., 79 , 1095
(1957)). According to these methods, the desired α, β-unsaturated carboxylic acid ester can be obtained at a high selectivity and a high yield without generating a β, γ-unsaturated product. When performing the method, it is necessary to use equal amounts of expensive reagents such as a halogenating agent and a sulfonating agent.Moreover, a large amount of eliminated salt is generated by the reaction, resulting in an increase in waste and an increase in post-treatment steps. This is very disadvantageous in terms of cost because it leads to complication.

Also, J. Am. Chem. Soc., 1947 , 1471 shows an example of the dehydration reaction of β-hydroxynitroalkane using phthalic anhydride. The reaction is performed using an acid anhydride, and the yield is only about 65%.

[0006]

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[0007]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to eliminate the use of expensive reagents, suppress the generation of waste,
It is an object of the present invention to provide an industrially advantageous method for producing an α, β-unsaturated carboxylic acid ester from a hydroxycarboxylic acid ester with high yield and high selectivity.

[0008]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have conducted intensive studies and as a result, in the presence of a catalytic amount of an aromatic polybasic carboxylic acid or an anhydride thereof, under high temperature conditions. By continuously reacting β-hydroxycarboxylic acid esters, it is possible to produce α, β-unsaturated carboxylic acid esters with high yield and high selectivity without using expensive reagents and with a small amount of waste. Conditions were established, and the present invention was completed.

That is, the gist of the present invention is to provide (1) a compound of the formula (I) in the presence of an aromatic polybasic carboxylic acid or an anhydride thereof.

[0010]

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(Wherein R ₁ , R ₂ and R ₃ each represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms, provided that R ₁ and R ₃ together form a ring R ₄ represents a linear or branched alkyl group having 1 to 3 carbon atoms), and the β-hydroxycarboxylic acid ester represented by the formula (1) is continuously supplied into the reaction system at 100 to 300 ° C. A process for producing an α, β-unsaturated carboxylic acid ester, wherein the reaction is carried out while rapidly removing the product from the reaction system, and (2) an aromatic polybasic carboxylic acid or its anhydride. The method according to the above (1), wherein the amount of the substance is 0.1 to 50 mol% based on the total charged amount of the β-hydroxycarboxylic acid ester as a raw material,
(3) The method according to the above (1) or (2), wherein the aromatic acid anhydride is phthalic anhydride or trimellitic anhydride, and (4) the β-hydroxycarboxylic acid ester is The above-mentioned (1), which is ethyl-hydroxycyclopentanecarboxylate (II).
To (3).

[0012]

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[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The aromatic polybasic carboxylic acid used in the present invention may be any one as long as it easily forms an acid anhydride and the boiling point of the acid anhydride is higher than the boiling point of the product. Specific examples of aromatic polybasic carboxylic acids and anhydrides from the viewpoint of global use include phthalic acid, terephthalic acid, trimellitic acid, pyromellitic acid, phthalic anhydride, trimellitic anhydride, and pyromellitic anhydride. And the like, more preferably phthalic anhydride and trimellitic anhydride. It is considered that the aromatic polybasic carboxylic acid is converted to an anhydride during the reaction and acts as a dehydrating agent, and it is preferable to use the anhydride directly rather than the acid. In addition, it is preferable that terephthalic acid or the like, which hardly forms an acid anhydride, coexist with the acid anhydride, because it also serves as an acid catalyst. These can be used alone or as a mixture.

The amount of the aromatic polybasic carboxylic acid or the anhydride thereof can be, for example, 0.1 to 50 mol% based on the total charged amount of the raw material β-hydroxycarboxylic acid ester. . Within this range, the reactivity is particularly high and the reaction rate is improved. Further, the production cost is low, and the generation of waste can be suppressed. Above all, 1-30
Mol% is more preferable, and 5 to 30 mol% is further preferable.

Various β-hydroxycarboxylic acid esters (general formula (I)) can be used as the raw material compound used in the present invention. The reaction is carried out while continuously removing the product outside the reaction system. Since it is necessary, a compound having a relatively low boiling point having a total carbon number of 15 or less is preferable. R ₄ in the general formula (I) has 1 to 3 carbon atoms.
The alkyl group is preferably a methyl group or an ethyl group, and particularly preferably an ethyl group. Specific examples of such β-hydroxycarboxylic acid esters include ethyl 3-hydroxybutanoate, ethyl 3-hydroxypentanoate, ethyl 3-hydroxyhexanoate, ethyl 2-hydroxycyclopentanecarboxylate, and ethyl 2-hydroxycyclohexanecarboxylate. And the like.
Particularly, ethyl 2-hydroxycyclopentanecarboxylate is preferred.

In the reaction of the present invention, the β-hydroxycarboxylic acid ester is continuously fed into the reaction system at 100 to 300 ° C. in the presence of an aromatic polybasic carboxylic acid or its anhydride, and The reaction is carried out while quickly removing the product out of the reaction system. Here, "continuously" means that the reaction is carried out by supplying the raw material β-hydroxycarboxylic acid ester to the reaction system under the condition that the product is quickly removed from the reaction system. Therefore, it does not merely mean that the raw materials are continuously supplied to the reaction system or that the products are continuously obtained. This is because, when the α, β-unsaturated carboxylic acid ester, which is a product, is left at a high temperature, a decomposition reaction, a polymerization reaction and the like occur to lower the yield. Therefore, for example, the reaction is carried out at a temperature not lower than the boiling point of the product and not higher than the boiling point of the acid anhydride, and the starting compound is continuously reacted under conditions such that the product is immediately removed from the reaction system after generation. A typical example of the “continuous” in the present invention is a case where the product is supplied to the system, and as a result, the product is continuously removed outside the reaction system. Therefore, as a mode of supplying the raw material compound, the raw material compound may be supplied continuously at a predetermined supply rate or may be supplied intermittently. The feed rate of the raw material compound may be determined appropriately according to the capacity of the apparatus. In addition,
In order to operate the apparatus stably, it is preferable to continuously supply the starting compound at a constant rate and obtain the product at a constant rate. Further, an inert gas may be blown into the system in order to assist in distilling out the product.

The reaction can be carried out without a solvent, but can also be carried out using a high-boiling solvent which is inert under the reaction conditions.
Examples of the inert high-boiling solvent include liquid paraffin, hydrocarbons such as alkyl-substituted benzene, alkyl benzoates, alkyl phthalates, and alkyl trimellites.

The reaction temperature varies depending on the reaction raw materials used, but can be appropriately selected within the range of 100 to 300 ° C., and is preferably 150 to 250 ° C. The reaction can also be carried out under reduced pressure depending on the starting compound used, and in this case, the degree of reduced pressure is 50 to 500 torr, more preferably 1 to 500 torr.
00 to 300 torr can be selected. According to the method of the present invention, waste products can be produced from β-hydroxycarboxylic acid esters from α, β-unsaturated carboxylic acid esters which are industrially useful as various synthetic intermediates without using expensive reagents. It can be produced in a small amount, with high yield, and with high selectivity.

Although the reaction product is obtained together with the desorbed water, it is preferable that these are separated quickly by a conventional method. Thus, the α, β-unsaturated carboxylic acid ester which is the object of the present invention can be produced with high purity and high yield.

[0020]

The present invention will be described in more detail with reference to the following Examples and Comparative Examples, but the present invention is not limited to these Examples and the like.

EXAMPLE 1 Phthalic anhydride (5.0 g, 33.8 mmol) and 2-phthalic anhydride were placed in a 100 ml four-necked flask equipped with a rotary stir bar, an internal thermometer, a Claisen distillation apparatus, and a metered addition apparatus.
Ethyl hydroxycyclopentanecarboxylate (5.3
g, 33.8 mmol). The temperature was raised to 220 ° C. with a mantle heater, and the pressure was reduced to 300 torr. When the ethyl cyclopentenecarboxylate and the desorbed water began to distill, ethyl 2-hydroxycyclopentanecarboxylate was dropped from the dropping device at a flow rate of 2 g / h for 8 hours to distill the product. After completion of the dropwise addition, heating was further continued under reduced pressure for 2 hours to distill off the product remaining in the system. The fraction was analyzed by GLC every 2 hours, and the results shown in Table 1 were obtained. Total charge 23.0 g, total distillate 19.4
g, recovery rate was 84.5%, reaction rate was 92 to 97%, and isomer selectivity was 94 to 95%. The yield (recovery rate x reaction rate x selectivity) was 76.3%.

[0022]

[Table 1]

Example 2 Trimellitic anhydride (24.3 g, 126 mmo) was placed in a 300 ml separable flask equipped with a rotary stir bar, an internal thermometer, a Claisen distillation apparatus, and a metering dropping apparatus.
l), ethyl 2-hydroxycyclopentanecarboxylate (20 g, 126 mmol), and di-2-ethylhexyl phthalate (80 g) as a solvent were charged.
The temperature was raised to 220 ° C with a mantle heater, and 200
The pressure was reduced to torr. When the ethyl cyclopentenecarboxylate and the desorbed water began to be distilled, ethyl 2-hydroxycyclopentanecarboxylate was continuously dropped from the dropping device at a flow rate of 5 g / h for 30 hours to distill the product. After completion of the dropwise addition, heating was further continued under reduced pressure for 2 hours to distill off the product remaining in the system. The fraction was analyzed by GLC every 4 hours and the results shown in Table 2 were obtained. Total charge 17
6.0 g, total distillate amount 164.0 g, recovery rate 93.2%,
The conversion was 96-98%, the isomer selectivity was 97-98%, and the yield was 88.6%.

[0024]

[Table 2]

Comparative Example 1 In a 200 ml four-necked flask equipped with a rotary stirring bar, an internal thermometer, a dropping funnel, and a Claisen distillation apparatus, 5 g of liquid paraffin and 20 g of the catalyst shown in Table 3 were added.
mol% (5% by weight of zeolite). Using a mantle heater, heat the reactor to 200 ° C.
The pressure was reduced to 0 torr. From the dropping funnel, ethyl 2-hydroxycyclopentanecarboxylate (5 g, 31.6 mm
ol) was added slowly over 30 minutes to distill off the product and desorbed water. The yield of the target product, regioisomer, and unreacted raw material was determined by GLC analysis of the fraction, and the results shown in Table 3 were obtained.

[0026]

[Table 3]

Example 3 In the same manner as in Example 1, phthalic anhydride (5.0
g, 33.8 mmol), terephthalic acid (0.56 g,
3.37 mmol) and ethyl 2-hydroxycyclopentanecarboxylate (5.3 g, 33.8 mmol). At 220 ° C. and 400 torr, ethyl 2-hydroxycyclopentanecarboxylate was added dropwise at 2 g / h for 8 hours. By performing GLC analysis of the fraction every 2 hours,
The results shown in Table 4 were obtained. Total charge 21.0 g, total fraction 16.34 g, recovery 77.8%, conversion 94-97
%, The isomer selectivity was 96 to 97%, and the yield was 71.7%.

[0028]

[Table 4]

Example 4 In the same manner as in Example 1, phthalic anhydride (5.0
g, 33.8 mmol) and ethyl 3-hydroxyhexanoate (5.4 g, 33.8 mmol).
At 200C and 200 torr, ethyl 3-hydroxyhexanoate was added dropwise at 2 g / h for 8 hours. By performing GLC analysis of the fraction every 2 hours, the results shown in Table 5 were obtained. Total charge 21.0 g, total fraction 16.48 g, recovery 78.5%, conversion 92-96%, isomer selectivity 96
~ 97%, yield was 71.6%.

[0030]

[Table 5]

Comparative Example 2 Phthalic anhydride (9.4) was placed in a 100 ml four-necked flask equipped with a rotary stirring bar, an internal thermometer and a Claisen distillation apparatus.
g, 63.5 mmol) and ethyl 2-hydroxycyclopentanecarboxylate (10.05 g, 63.5 mm)
ol). The temperature was raised to 220 ° C. by a mantle heater, and the pressure was reduced to 300 torr, and the resulting ethyl cyclopentenecarboxylate and desorbed water were distilled off (fraction: 6.4 g, recovery: 64%). According to GLC analysis of the fraction, the β, γ-isomer was 4.9%, the α, β-isomer was 87.8%, the unreacted raw material was 5.9%, the conversion was 94.1%, and the isomer selectivity was 95%. And the yield was 57.2%.

[0032]

According to the method of the present invention, an α, β-unsaturated carboxylic acid ester can be industrially advantageously produced in a high yield and a high selectivity.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C07C 69/74 C07C 67/327 C07C 69/533 CA (STN) WPI / L (QUESTEL)

Claims (4)

(57) [Claims] 1. A compound of the formula (I) in the presence of an aromatic polybasic carboxylic acid or an anhydride thereof. (Wherein, R ₁ , R ₂ , and R ₃ each represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms, provided that R ₁ and R ₃ together form a ring R
₄ represents a linear or branched alkyl group having 1 to 3 carbon atoms. Wherein the β-hydroxycarboxylic acid ester represented by the formula (1) is continuously supplied into the reaction system at 100 to 300 ° C. and the reaction is carried out while removing the product outside the reaction system. A method for producing an unsaturated carboxylic acid ester. 2. The method according to claim 1, wherein the amount of the aromatic polybasic carboxylic acid or its anhydride is 0.1 to 50 mol% based on the total amount of the β-hydroxycarboxylic acid ester. the method of. 3. An anhydride of an aromatic polybasic carboxylic acid,
3. The method according to claim 1, wherein the method is phthalic anhydride and / or trimellitic anhydride. 4. A β-hydroxycarboxylic acid ester,
The method according to any one of claims 1 to 3, which is ethyl 2-hydroxycyclopentanecarboxylate (formula (II)). Embedded image