JPS6042778B2 - Method for producing alkoxyalkylidene compounds - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Methods for producing the corresponding alkoxyalkylidene compounds by reacting orthoacid esters with active methylene compounds have been described in numerous literatures.

For example, regarding the production of alkoxymethylene malone, which is one of the above compounds, and acid ester, JP-A No. 51-4123
It is stated in the No. This method involves reacting an orthoformic acid ester and a malonic acid ester in the presence of a mixed catalyst of (1) a carboxylic acid or carboxylic acid anhydride and (2) a Lewis acid such as zinc chloride or iron chloride. Although this method is advantageous in that a high-quality product can be obtained, the inventors' studies revealed that the method has the following problems. 1 The catalyst used, chloride, is highly corrosive; therefore, even stainless steel, which is the most typical corrosion-resistant material, is corroded during the reaction, and some of it is eluted into the reaction solution, causing the reaction. It is necessary to produce the above-mentioned compound by a method that does not cause any fear of corrosion of the reactor, since it has an unfavorable effect on the reactor and the strength of the reactor itself. 2. Furthermore, in this method, it is necessary to recover the end-reacted orthoformate ester after the completion of the reaction, perform a filtration operation for the reaction, and after distributing the catalyst from person to person, perform fractional distillation of the product.

If the catalyst is not filtered out, the product will decompose and the yield will decrease. When viewed as an industrial production method, such operations are not necessarily advantageous production conditions, as they require increased complexity and time, such as thermal filtration and temporary suspension of vacuum distillation. However, as a result of extensive research to solve this problem, the present inventors have found that the formula R_ in the presence or absence of a solvent.

C(OR_,)O [here, alkyl group, R_. is hydrogen,
Indicates an alkyl group, an allyl group, and an aralkyl group. ] and the formula H2C<:゜ [Here, R3 and R4 represent -COOR. ] by reacting with an active methylene compound represented by the general formula R2♀6〈;゛
[In the method for producing an alkoxyalkylidene compound in which R1, R2, R3, and R4 are represented as above,
When (1) a lower carboxylic acid anhydride having 1 to 5 carbon atoms and (2) a zinc salt of a carboxylic acid or a zinc salt of an inorganic oxyacid are used as catalysts, corrosion of the equipment can be completely prevented and The reaction can proceed smoothly without being inhibited by elution of the material of the device, and the reaction solution can be distilled without separating the catalyst from the reaction solution, making it easy to obtain the target compound. The present inventors have completed the present invention by discovering the novel fact that the yield of an alkoxyalkylidene compound can be improved by using a hydrocarbon solvent during such a reaction. Catalysts used in the present invention that belong to (1) include acetic anhydride,
Examples include propionic anhydride and succinic anhydride.

Furthermore, those belonging to (2) include zinc acetate, zinc sulfate,
Examples include zinc phosphate. Among such catalysts, a combination of acetic anhydride, zinc monoacetate, and acetic anhydride, zinc monosulfate, is particularly effective. The amount of the catalyst to be used is 0.05 to 0.5 mol of component (1) to 0.5 mol of component (2) based on the orthoacid ester.
The amount is preferably about 00001 to 0.001 mol. Further, examples of the hydrocarbon solvent used in the present invention include n-octane, benzene, toluene, o-xylene, etc., and toluene and o-xylene are particularly effective.

The dosage of such solvent is 8 per mole of orthoate ester.
0 to 1000 m1 is preferable. Examples of orthoacid esters used in the present invention include methyl orthoformate, ethyl orthoacetate, ethyl orthoformate, orthopropionate, and a typical example of the active methylene compound includes diethyl malonate. The process of the present invention is particularly useful in producing ethoxymethylene diethyl malonate from ethyl orthoformate and diethyl malonate.

In carrying out the method of the present invention, the orthoacid ester, the active methylene compound, and preferably a hydrocarbon solvent are mixed and heated under stirring.

The charging ratio of raw materials is orthoate ester diactive methylene compound = 11 to 3:1 (mole ratio), preferably 1.1:1 to
A ratio of about 2.0:1 is appropriate.

The reaction temperature is preferably 100 to 160°C, and the reaction time is preferably 1 to U hours. The yield can be improved by distilling the alcohol by-produced in the above reaction out of the system and by ensuring that the solvent is always present in the reaction system when a solvent is used. For this purpose, it is usually sufficient to select a hydrocarbon solvent that has a boiling point higher than the reaction temperature and the boiling point of the alcohol produced, but this is not necessarily the case. Available for use. When using such a solvent with a relatively low boiling point, a rectification device may be attached to the reaction tank to distill out only the produced alcohol, and the reaction may be carried out while the solvent is refluxed. In addition, when using a solvent with a boiling point much lower than the reaction temperature, if there is a risk that it will be difficult to raise the temperature to the desired reaction temperature, reduce the amount of solvent used or charge it in parts. It can be solved. Further, even if the produced alcohol forms an azeotropic composition with the solvent used and the solvent is distilled off together with the produced alcohol, the solvent may be added as appropriate during the reaction. The reaction can be carried out under normal pressure, increased pressure, or reduced pressure. At the end of the reaction, the reaction solution is distilled under reduced pressure to obtain the desired product.

The alkoxyalkylidene compounds obtained in the present invention are useful as intermediates for pharmaceuticals or other organic synthetic products.

Next, the method of the present invention will be explained in more detail by giving examples.Example 1 Stirrer, dropper, and rectifying tube (2.0 cmφ x 30C77
50077 with features! In a L flask, 1.3 mol of ethyl orthoformate, 1.0 mol of diethyl malonate, 0.10 mol of acetic anhydride, 0.0001 mol of zinc acetate (2.19y as a 1% ethanol solution) 100 ml of o-xylene
The reaction was carried out at 145 to 155°C for 5 hours, and the reaction was further heated to 155°C for 0. The reaction was continued for an hour.

The obtained reaction-completed liquid was distilled under reduced pressure and heated to 130-135℃/
A 5wnHg fraction was collected. The yield of diethyl ethoxymethylene malonate based on the consumed ethyl orthoformate is 7
The yield was 85% based on diethyl malonate. In addition, the following experiment was conducted to test the corrosivity of the reaction solution. A polished mild steel plate (3 × 50 mm × 1. h) that had been degreased and dried with acetone was immersed in 200 ml of the crude reaction solution for 165 ml.
After 7 days at ℃, the amount of corrosion was measured by weight loss before and after immersion, and the corrosion rate was determined by Yldlhr.

The results showed that the corrosion rate was 0 in the case of the present invention, and there was no change in the surface of the test piece. On the other hand, as Control Example 1, the same experiment as Example 1 was conducted except that zinc chloride was used instead of zinc acetate.

(However, before distilling the reaction solution, the terminally reacted ethyl orthoformate was expelled and the zinc chloride was removed.) The yield of ethoxymethylene diethyl malonate relative to ethyl orthoformate was 76%, and the yield relative to diethyl malonate was 76%. was 81%.

Further, the corrosion rate was 0.01yId1hr, and the surface of the test piece turned black, suggesting that corrosion had progressed. Control example 1
If zinc chloride was not separated in the furnace, the yield decreased to 70%. Example 2 The same experiment as in Example 1 was carried out except that zinc sulfate was used instead of zinc acetate.

The yield of diethyl ethoxymethylene malonate based on ethyl orthoformate was 75%, and the corrosion rate was O. Example 3 The same experiment as in Example 1 was carried out except that the use of o-xylene was omitted.

The yield of diethyl ethoxymethylenemalonate based on ethyl orthoformate was 70%, and corrosion was 0. As Control Example 2, when zinc chloride was used in place of zinc acetate in the above example, the yield of diethyl ethoxymethylene malonate was 70%.
The corrosion rate was 0.01y1d1hr. (However, zinc chloride was removed before distillation after the reaction.) When the reaction solution was distilled in the presence of zinc chloride, the yield of the target product decreased to 65%.

Example 4 Same device as Example 1 (however, the distillation tube is 2.2cfnφ×108
C! RL), 1.5 mol of ethyl orthoformate, 1.0 mol of diethyl malonate, 0.1 mol of acetic anhydride, and 0.0 mol of zinc acetate.
0001 mol and 110 ml of benzene were charged.

1 hour at 120-140℃, further 7 hours at 140℃, 1
The reaction was carried out at 40-160°C for 2 hours.

(During the reaction, 770 ml of benzene was added dropwise.
) The yield of diethyl ethoxymethylenemalonate was 70%. The corrosion rate was 0. Example 5 The same method as Example 1 was carried out except that toluene was used in place of o-xylene in Example 1.

Claims (1)

[Claims] 1. In the presence or absence of a solvent, the formula R_2C(OR_
1)_3 [where R_1 is an alkyl group, R_2 is hydrogen,
Indicates an alkyl group or an allyl group. ] Orthoacetate formula ▲ mathematical formula, chemical formula,
There are tables etc. ▼ [Here, R_3 and R_4 are -COOR
Indicates _1. ] By reacting with an active methylene compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [R_
1, R_2, R_3, R_4 are the same as above] In the method for producing an alkoxyalkylidene compound represented by (1) a lower carboxylic acid anhydride having 1 to 5 carbon atoms and (2) a zinc salt of a carboxylic acid as a catalyst. Or, a method for producing an alkoxyalkylidene compound, which comprises using a zinc salt of an inorganic oxyacid.