JPH0791225B2 - Method for producing alkyl 2-ethoxymethylene acetoacetate - Google Patents

Description

The present invention relates to an improved process for obtaining alkyl 2-ethoxymethyleneacetoacetate in high yield.

Alkyl 2-ethoxymethyleneacetoacetate is useful as an intermediate of a pyrazole derivative used as a fungicide for agriculture and horticulture.

[Problems to be Solved by Prior Art and Invention]

It is well known that, when an alkoxymethylene compound is produced, a condensation reaction between an orthoformate ester and a compound containing a reactive methylene group is carried out in the presence of acetic anhydride (“Berichte Berchte”). ) No.
26, 2729 (1893), "Annalen der chemie", 297, 19 (1897).
Year)).

For example, in Pharmaceutical Journal, vol.79, pages 836 to 8 (1959), a mixture of ethyl acetoacetate ester, acetic anhydride, and ethyl orthoformic acid ester is reacted at 140 ° C. to obtain the desired product, but the yield is about As low as 55%.

Further, JP-B-57-40820 discloses that an excess amount of triethyl orthoformate ester, malonic acid dinitrile and a catalytic amount of acetic anhydride are charged as a condensation reaction between a compound containing a methylene group and an orthoformate ester and heated. A method of causing a reaction and continuously supplying a catalytic amount of acetic anhydride during the progress of the reaction is exemplified.

However, in the case of producing alkyl 2-ethoxymethyleneacetoacetate from alkyl acetoacetate and ethyl orthoformate in the presence of acetic anhydride, the reaction does not proceed smoothly even if acetic anhydride is added by the above method. However, since the yield is low, a manufacturing method for obtaining the target product with a high yield has been demanded.

[Means for Solving the Problems]

The present inventors have conducted extensive studies to solve the above-mentioned problems, and as a result, in the presence of acetic anhydride, when producing 2-ethoxymethylene acetoacetate from alkyl acetoacetate and ethyl orthoformate, ,
It was found that the target product can be obtained in a high yield by continuously adding an excess amount of acetic anhydride during the reaction and further carrying out the reaction while distilling off the light-boiling substance formed during the progress of the reaction. Was completed.

That is, in the present invention, in the production of 2-ethoxymethylene acetoacetate using alkyl acetoacetate and ethyl orthoformate in the presence of acetic anhydride, acetic anhydride is continuously added to a mixture of alkyl acetoacetate and ethyl orthoformate. In addition to the above, the reaction is carried out while distilling off the produced light-boiling substance, which is a method for producing alkyl 2-ethoxymethyleneacetoacetate.

Hereinafter, the present invention will be described in detail.

The alkyl acetoacetate used in the present invention is methyl acetoacetate, ethyl acetoacetate, propyl acetoacetate, butyl acetoacetate, pentyl acetoacetate and the like.

In the present invention, 1.0 to 2.0 mol of ethyl orthoformate is added to 1 mol of alkyl acetoacetate.

In this case, if the amount of ethyl orthoformate is less than 1.0 mol, the reaction yield is significantly reduced.

If the amount is more than 2.0 mol, the yield tends to increase,
It is not economically advantageous, and the molar ratio of alkyl orthoformate is preferably 1.2 to 1.5 mol.

The reaction temperature is usually 90 to 140 ° C. If the temperature is lower than 90 ° C., the yield is low, and if it exceeds 140 ° C., the yield is low.

In the present invention, acetic acid and alkyl acetate are by-produced.

In this case, since the product 2-ethoxymethylene acetoacetate is decomposed by the presence of acetic acid,
In order to reduce the production of acetic acid as much as possible, acetic anhydride is gradually added, and the produced acetic acid is distilled out of the system as much as possible.

Therefore, in this reaction, acetic anhydride is continuously added.

The amount of acetic anhydride to be added is usually 3.0 to 4.0 mol per 1 mol of alkyl acetoacetate. When the molar ratio is less than 3.0, the reaction yield decreases, and when the molar ratio exceeds 4.0, the yield does not change. The continuous addition of acetic anhydride is preferably carried out at 0.016 to 0.018 mol / min with respect to 1 mol of alkyl acetoacetate. If the amount is larger than this, bumping due to a vigorous reaction is likely to occur, and thus it is difficult to continue the reaction. If the amount is smaller than this, thermal decomposition of the target substance occurs concurrently, and the yield tends to decrease.

During the course of this reaction, a fractionating column and a condenser are installed in the reactor, and the light-boiling substances by-products of the reaction are cooled in the condenser through the fractionating column. The entire amount of the reflux liquid is returned to the reactor to carry out the reaction. By this operation, the light boiling substance containing acetic acid produced is discharged out of the system.

The reaction time is usually 2 to 3 hours. The reaction solution is then concentrated under reduced pressure at about 80 ° C. and concentrated to distill off the alkyl acetate and acetic acid. By this operation, the purity of the target product in the main fraction is usually 98% or more, and it can be used as it is in a usual reaction, but it can be further purified if necessary.

Also, the middle distillate can be used for the reaction depending on the purity.

〔Example〕

 Hereinafter, the present invention will be described in detail with reference to Examples.

Example 1 A fractional distillation column (diameter 3 cm × height 25 cm,
527 g (5.58 mol) of ethyl acetoacetate and 994 g (6.71 mol of ethyl orthoformate) in a 5 round bottom flask equipped with a condenser (diameter 3.5 cm x height 45 cm) for cooling the effluent from the column. ) Was charged, the mixture was heated and stirred, and the temperature was raised to 120 ° C.

The reaction solution was kept at 113 to 120 ° C., acetic anhydride was continuously added at a rate of 9.5 g / min, and 1714 g (16.8 mol) was charged in 3 hours. Further, the reaction was continued for 2 hours at 110 to 115 ° C. and aged.

The light-boiling substances (acetic acid and ethyl acetate) by-produced during the reaction were separated by a fractional distillation column, and 762 g of light-boiling substances having a boiling point of 73 to 81 ° C were distilled out of the system.

The end point of the reaction was carried out by gas chromatography, and aging was carried out after the reaction until ethyl acetoacetate was not detected.

After the completion of the reaction, the mixture is concentrated at 40 mmHg at 80 ° C for 2 hours, the remaining ethyl acetate and acetic acid are distilled off, and then vacuum distilled to separate a fraction having a boiling point of 106.5 to 115 ° C (2 to 3 mmHg) as the main fraction. Then, ethyl 2-ethoxymethyleneacetoacetate was obtained in a yield of 994.0 g (GC analysis purity: 99.1% by weight) and a yield of 90%.

Example 2 Except that 648 g (5.58 mol) of methyl acetoacetate was used.
The reaction was carried out in the same manner as in Example 1, and after the post-treatment, vacuum distillation was carried out to obtain a fraction having a boiling point of 173 to 174 ° C. (45 mmHg) as a main fraction. Yield of methyl 2-ethoxymethylene acetoacetate
It was 874..3 g (yield 91%), and the purity by gas chromatography was 99%.

Example 3 The reaction was carried out in the same manner as in Example 1 except that 961 g (5.58 mol) of isopentyl acetoacetate was used. After post-treatment, vacuum distillation was performed to obtain 1121 g (88% yield) as the main fraction.
2-ethoxymethylene acetoacetate isopentyl was obtained. The purity by gas chromatography was 99.3%.

Comparative Example 1 In a 5 round bottom flask equipped with a Dimroth condenser, a mixture of 727 g of ethyl acetoacetate, 994 g of ethyl orthoformate and 1714 g of acetic anhydride was gradually heated with stirring and heated to 133 ° C. in 2 hours. did.

The temperature was raised to 133 ° C., 10 minutes later, vigorous reflux was started, and by-products rose to the upper part of the condenser.

Since there is a possibility of bumping, the reaction solution was rapidly cooled to 30 ° C., again required 1 hour, heated to 133 ° C., and reacted at 106 to 133 ° C. for 1.5 hours for aging. At 106 to 133 ° C., the light boiling substance was distilled out of the system over 4 hours.

Then, post treatment was carried out in the same manner as in Example 1 to obtain a yield of 73
The target product was obtained with 4 g (purity 99.5% by weight) and a yield of 70.3%.

Comparative Example 2 The reactor of Example 1 was charged with 994 g of ethyl orthoformate and 1714 g of acetic anhydride and heated to 130 ° C. Next, 727 g of ethyl acetoacetate was continuously charged at 115 to 130 ° C for 3.0 hours, and further 1
The reaction was carried out at 15 to 130 ° C. for 2 hours for aging.

During the reaction, the light boiling substance by-produced was distilled out of the system by the same method as in Example 1. Then, post-treatment was carried out in the same manner as in Example 1 to obtain 712.6 g (purity: 96.13% by weight) of the target product in a yield of 75.0%.

Comparative Example 3 727 g of ethyl acetoacetate and 1714 g of acetic anhydride were charged into the reactor of Example 1 and heated to 120 ° C. and heated.

After the reaction, keep the temperature at 111-120 ℃, and add 994g of ethyl orthoformate to 3
The mixture was continuously charged for an hour, and then the reaction was aged at 111 to 120 ° C. for 2 hours. During this period, the by-product light boiling material was removed from the system by the same method as in Example 1.

After that, the same post-treatment as in Example 1 was performed to obtain 679.8 g (purity 9
The target product was obtained with a yield of 64.6%.

〔The invention's effect〕

When producing 2-ethoxymethylene acetoacetate from alkyl acetoacetate and ethyl orthoformate in the presence of acetic anhydride, acetic anhydride is continuously added during the reaction, and at the same time, the light boiling substance by-produced is reacted while distilling off. The method of the present invention is
Compared to other methods in which the method of adding raw materials and catalysts is changed, bumping does not occur, the reaction proceeds smoothly, and it is an excellent production method in which the target product can be obtained in high yield.

Claims (2)

[Claims] 1. When producing 2-ethoxymethylene acetoacetate using alkyl acetoacetate and ethyl orthoformate in the presence of acetic anhydride, acetic anhydride is continuously added to a mixture of alkyl acetoacetate and ethyl orthoformate. In addition to the above, the method for producing alkyl 2-ethoxymethylene acetoacetate is characterized in that the reaction is carried out while distilling the produced light-boiling substance. 2. The process according to claim 1, wherein the alkyl of 2-ethoxymethylene acetoacetate has a carbon number of C _{1 to} C ₅ .