JPH03106849A - Production of alkyl 2-ethoxymethyleneacetoacetate - Google Patents

Abstract

PURPOSE:To obtain the subject compounds useful as an intermediate for synthesis of a pyrazole derivative used as an agricultural germicide in a high yield by reacting an alkyl acetoacetate with ethyl orthoformate while continuously adding acetic anhydride catalyst thereto and distilling off generated low boiling substances. CONSTITUTION:In a reaction between an alkyl acetoacetate and ethyl orthoformate using acetic anhydride as a catalyst, the reaction is carried out while continuously adding acetic anhydride at 9-10g/min. and distilling off generated low boiling substances containing acetic acid. By addition of acetic anhydride within the above-mentioned range, a bumping due to a vigorous reaction can be prevented and thermal decomposition of the objective substance can be lowered. In addition, the decomposition can be inhibited by distilling off acetic acid. Based on 1mol alkyl acetoacetate, 1.2-1.5mol ethyl orthoformate and 3.0-4.0mol acetic anhydride are preferably used.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a process for producing alkyl 2-ethoxymethyleneacetoacetate. More specifically, it relates to an improved production method for obtaining the desired product in high yield. 2-ethythymethyleneacetoacetate is useful as an intermediate for pyrazole derivatives used as agricultural and horticultural fungicides. [Problems to be solved by conventional techniques and inventions] Conventionally,
It is well known that when producing an alkoxymethylene compound, a condensation reaction between an orthoformate and a compound containing a reactive methylene group is carried out in the presence of acetic anhydride as a catalyst. "He Q") Chez Berchte J (Ber
ichte) Volume 26, Page 2729 (1893),
"Annalen der Hemie J"
der chemie) Volume 297, Page 19 (1
897). US Pat. No. 2,824,121 describes a method for producing an alkoxymethylene compound from an orthoformic acid ester and a compound containing a reactive methylene group in the presence of acetic anhydride as a catalyst. However, this method
Both reactions have the disadvantage that the partial conversions are incomplete with respect to each other and produce large amounts of by-products which significantly reduce the yield.

Furthermore, Pharmaceutical Journal vol 179, pages 836-8, (1959)
The desired product was obtained by reacting a mixture of acetoacetic acid ethyl ester, acetic anhydride, and orthoformic acid ethyl ester at 140°C, but the yield was as low as about 55%. Also, special public service 1977-
In the specification of No. 40820, triethyl orthoformate, dinitrile malonate, and acetic anhydride are charged and reacted with heating for a condensation reaction between a methylene group compound and an orthoformate. A method of continuously supplying acetic anhydride during the progress of the reaction is also exemplified.

In each of the above methods, acetic anhydride, which is used as a catalyst, can be added from the beginning or added to it at the beginning. , and a method of continuously adding it during the reaction. When producing alkyl 2-ethoxymethyleneacetoacetate from alkyl acetoacetate and ethyl orthoformate, when acetic anhydride is added using the method described above, the reaction does not proceed smoothly and the yield is low. Therefore, a high-yield method was required. [Means for Solving the Problems] As a result of intensive studies, the present inventors found that acetic anhydride as a catalyst was continuously added during the reaction, and further, the reaction was carried out while distilling off certain light boiling substances produced during the progress of the reaction. We have completed the present invention by discovering that the desired product can be obtained in high yield by carrying out this process. That is, in the present invention, when producing alkyl 2-ethoxymethyleneacetoacetate using alkyl acetate, ethyl orthoformate, and acetic anhydride as a catalyst, acetic anhydride is continuously added, and while distilling off the light boiling products produced, This is a method for producing alkyl 2-ethoxymethyleneacetoacetate, which is characterized by carrying out a reaction. The present invention will be explained in detail below. The alkyl acetoacetate used in the present invention includes methyl acetoacetate, ethyl acetoacetate, proyl acetoacetate, stutyl acetoacetate, pentyl acetoacetate, and the like. In the present invention, 1.0 to 2.0 mol of ethyl orthoformate is added per 1 mol of alkyl acetoacetate. In this case, if the amount of ethyl orthoformate is less than 1.0 mol, the reaction yield will decrease significantly. Further, if the amount is more than 2.0 mol, although the yield tends to increase, it is not economically advantageous, and the molar ratio of the alkyl orthoformate is preferably 1.2 to 1.5 mol. The reaction temperature is usually 90 to 140°C; below 90°C, the yield is low;
Moreover, even if the temperature exceeds 140°C, the yield decreases.

In the reaction between alkyl acetoacetate and ethyl orthoformate using acetic anhydride as a catalyst to obtain alkyl 2-ethoxymethyleneacetoacetate, acetic acid and alkyl acetate are produced as by-products.

In this case, the presence of acetic acid accelerates the decomposition of 2-ethoxymethyleneacetoacetate alkyl in the raw bottom, so
In order to reduce the production of acetic acid as much as possible, the yield is better if acetic anhydride is added gradually and the produced acetic acid is distilled out of the system as much as possible.

Therefore, in this reaction, acetic anhydride is added continuously. The amount of acetic anhydride to be added is usually 3.0 to 4.0 moles per mole of alkyl acetoacetate. 3.0
When the molar ratio is less than 4.0, the reaction yield decreases, and even when the molar ratio exceeds 4.0, the yield remains the same. Continuous addition of acetic anhydride is carried out at a rate of 9 to 10 g/min. If the amount is more than this, bumping is likely to occur due to violent reaction, making it difficult to continue the reaction, and if it is less than this, thermal decomposition of the target product will occur simultaneously, and the yield will tend to decrease. During the course of this reaction, a fractionating column and a condenser are installed in the reactor, and the light boiling matter of the reaction by-product is cooled in the condenser through the fractionating force ram. The reaction is carried out while the entire amount of the reflux liquid is returned to the reactor. By this operation, the produced light boiling substances including acetic acid are discharged from the system.

The reaction time is usually 2 to 3 hours. The reaction solution was then maintained at approximately 80°C under reduced pressure. Condensation is performed to distill off alkyl acetate and acetic acid. In this operation, the opacity of the 11 products in the main fraction is usually 980≦1; it can be used as it is for ordinary reactions, but it may be further purified if necessary. You can also. Furthermore, middle distillates can also be used in reactions depending on their purity.

[Effect]

When producing an alkoxymethylene compound by the reaction of a reactive methylene group compound and orthoformic acid ester, there are two methods: adding acetic anhydride as a catalyst at the beginning, adding it continuously during the reaction, or adding other raw materials. Methods such as adding it during the reaction also caused bumping, making it difficult to make the reaction proceed smoothly, and the yield was not good. In the method of the present invention, in which acetic anhydride is continuously added and light boilers are removed, decomposition of the target product can be prevented, rapid reaction can be moderated, and the reaction can be carried out in high yield. [Example] Hereinafter, the present invention will be explained in detail with reference to Examples.

Example l A fractionating column l. (Diameter 3rI
+1 x height 25c+i, Rassi ring packing) is connected to a condenser (diameter 3.
727 g (5.58 mol) of ethyl acetoacetate was added to a 52 round bottom flask fitted with a 50 x high 45 ell)
994 g (6.71 mol) of ethyl orthoformate was charged, and the temperature was raised to 120°C by heating and stirring. Keep the reaction solution at 113-120°C and add 9.5g/acetic anhydride.
1714g (16.8mol)
was loaded in 3 hours. The reaction was further continued for 2 hours at 110 to 115°C to ripen.

Light boiling substances (acetic acid and ethyl acetate) produced as by-products during the reaction are separated using a fractionation column, and the light boiling substances with a boiling point of 73 to 81°C are separated.
2 g was distilled out of the system.

The end point of the reaction was determined by gas chromatography, and the reaction was carefully monitored until ethyl acetoacetate was not detected. After the reaction was completed, a concentration operation was carried out for 80"02 hours at 40a+mHg, and after distilling off the remaining ethyl acetate and acetic acid, vacuum distillation was performed to obtain a boiling point of 106.5-115℃ (2-115℃).
3IIlmHg) was separated as the main fraction, yielding 9
94.0g (GC analysis purity 99.1% by weight), yield 90
% of 2-ethoxymethyleneacetoacetate was obtained.

Example 2 The reaction was carried out in exactly the same manner as in Example 1, except that 648 g (5.58 mol) of methyl acetoacetate was used, and after post-treatment, distillation was carried out under reduced pressure to give a product with a boiling point of 173-174°C (45
mmHg) was obtained as the main distillate. The yield of methyl 2-ethoxymethyleneacetoacetate was 874.3 g (9% yield), and the purity as determined by gas chromatography was 99%.

Example 3 A reaction was carried out in exactly the same manner as in Example 1, except that 961 g (5.58 mol) of isopentyl acetoacetate was used. After post-treatment, vacuum distillation is performed to obtain 1121 as the main fraction.
g (yield: 88%) of isopentyl 2-ethoxymethyleneacetoacetate was obtained. Purity by gas chromatography was 99.3χ. Comparative Example 1 In a 5 liter round bottom flask equipped with a Dimroth condenser, 727 g of ethyl acetoacetate and 99 g of ethyl orthoformate were added.
A mixture of 4g of acetic acid and 1714g of acetic anhydride was gradually heated with stirring to raise the temperature to 133°C over 2 hours.

The temperature was raised to 133°C, and after 10 minutes, vigorous reflux began and by-products rose to the top of the condenser.

Because of the possibility of bumping, the reaction limb was rapidly cooled to 30°C, and then heated again to 133°C over 1 hour.
The mixture was reacted at 33° C. for 1.5 hours and aged. 106-1
Light boiling substances were distilled out of the system at 33°C over a period of 4 hours.

Thereafter, post-treatment was performed in the same manner as in Example 1, yielding 1
The desired product was obtained in an amount of 34 g (purity 99.5 weight 2) and a yield of 70.3%.

Comparative Example 2 The reaction apparatus 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 then further charged for 2 hours at 115 to 130°C.
I made a time reaction and practiced the precepts.

During the reaction, by-produced light boiling substances were distilled out of the system in exactly the same manner as in Example 1. Thereafter, post-treatment was carried out in the same manner as in Example 1 to obtain 712.6 g (purity: 96.13% purity) of the desired product with a yield of 75.0%.

Comparative Example 3 727 g of ethyl acetoacetate and 1,714 g of acetic anhydride were charged into the reactor of Example 1 and heated to 120°C.
The reaction solution was maintained at 111-120°C, 994 g of ethyl orthoformate was continuously charged over 3 hours, and the reaction was further aged at 111-120°C for 2 hours. During this time, by-produced light boiling substances were removed from the system in exactly the same manner as in Example 1. Thereafter, the same post-treatment as in Example 1 was carried out, and 679.8g (
The target product was obtained with a purity of 98.7% by weight (χ) and a yield of 64.6χ. [Effect of the invention] As can be seen from the examples and comparative examples, ethyl acetoacetate and
When producing alkyl 2-ethoxymethyleneacetoacetate using ethyl orthoformate as a raw material and acetic anhydride as a catalyst, acetic anhydride is added continuously during the reaction, and at the same time the reaction is carried out while distilling off light boiling substances produced as by-products. The method consists of raw materials,
Compared to methods that change the catalyst addition method, bumping does not occur,
This is an excellent manufacturing method that allows the reaction to proceed smoothly and yield the desired product in high yield.

Claims (2)

[Claims] (1) When producing alkyl 2-ethoxymethyleneacetoacetate using alkyl acetoacetate, ethyl orthoformate, and acetic anhydride as a catalyst, continuously adding acetic anhydride,
A method for producing alkyl 2-ethoxymethyleneacetoacetate, which comprises carrying out the reaction while distilling off produced light boiling products. (2) The manufacturing method according to claim 1, wherein the alkyl of the alkyl 2-ethoxymethyleneacetoacetate is C_1 to C_5.