JPS5840936B2 - Production method of malonic acid diester - Google Patents

Description

Detailed Description of the Invention The present invention provides a method for producing malonic acid diester by reacting monochloroacetate with -carbon oxide, alcohol and a basic substance in the presence of a cobalt carbonyl catalyst. The present invention relates to a method for producing malonic acid diester, which is characterized by using a substance and adding monochloroacetic ester in portions.

Malonic acid diester is an important product as an intermediate for pharmaceuticals and agricultural chemicals. Conventionally, an organic halogenide is converted into -carbon oxide, It is known from Japanese Patent Publication No. 40-10967 to produce esters of organic acids by reacting with alcohols and basic substances, and monochloroacetic ester is also used as a raw material for this, but its yield is low. .

As a result of various research into the cause of this, we found that although it depends on the catalyst activity, the influence of basic substances is particularly large, and that carbonates and/or bicarbonates of alkali metals are preferable in terms of reaction and cost. If only a specific basic substance is used in the reaction, the pH may drop in the early stage of the reaction or the catalyst may become deactivated depending on the reaction method.
These improvements are desired.

The present invention aims to solve these drawbacks, and furthermore, specifies the type, proportion, and amount of the basic substance when reacting monochloroacetic ester, carbon oxide, alcohol, and basic substance in the presence of a cobalt carbonyl catalyst. The pH is automatically controlled by adding monochloroacetic acid ester in portions, and the reaction proceeds without any problems with catalyst activity, resulting in stable operation and high yield production of malonic acid diester. This is what we are trying to provide.

That is, the present invention provides, in the presence of a cobalt carbonyl catalyst,
When producing malonic acid diester by reacting monochloroacetate with carbon monoxide, alcohol and a basic substance, an alkali metal carbonate and/or bicarbonate and an alkali metal hydroxide are used as the basic substance. The ratio is 95.0 to 99.5: 5.0 to 0.5 by weight.
The amount of the basic substance to be used is stoichiometric or more, preferably 1 to 1.
It is characterized in that it is present in a 3-fold molar amount and that monochloroacetic ester is added in portions.

The present invention will be explained in more detail below.

First, the following two types of basic substances are used in combination.

(1) is an alkali metal carbonate and/or bicarbonate, preferably Na2CO3, K2CO3, Na
HCO3 and KHCO3.

(2) The alkali metal hydroxide is preferably NaO
It is H1KOH.

The amount of base to be used is at least stoichiometric, preferably 1.0 to 1.3 times the amount of hydrogen chloride produced as a by-product in the reaction, that is, the amount of monochloroacetic ester. The base substances belonging to the group are used in a weight ratio of 95 to 99.5 (2) The bases belonging to the group are used in a weight ratio of 5 to 0.5.

If it exceeds 5, the time of high pH from the initial reaction stage will be long,
Side reactions occur and the selectivity of malonic acid diester decreases.

If it is less than 0.5, the pH may be too low or the catalyst may be deactivated, which is not preferable.

Preferably basic substances 95 to 99 belonging to (1), (2)
Bases 5 to 1 belong to .

If a basic substance belonging to (2) is used alone, side reactions will easily proceed, so it is virtually impossible to charge it all at once, and it is necessary to dissolve it in a solvent and add it to the reaction system in portions. However, by using it in combination with (1), it can be added all at once, without any of the above problems, and good selectivity can be obtained.

The reaction method is to charge the alcohol, catalyst, and basic substance all at once, and then add monochloroacetic ester in portions.

In the method of charging all the raw materials at once, a stable pH cannot be obtained, problems arise in temperature control due to heat generation, and further deterioration of reaction results is unavoidable in terms of operation.

A preferred cobalt carbonyl catalyst used in the present invention is dicobalt octacarbonyl (hereinafter referred to as Co2 (C
o)s) and Co(CO)4 in alcohol or acetone, particularly preferably Co(C
o) Alcohol or acetone solution of 4.

The molar ratio of cobalt carbonyl catalyst and monochloroacetic ester is 1:1 to 1:400, preferably 1:4 to 1:400.
It is 1:100.

The ester moiety of the monocross acetate is not particularly limited, but is preferably methyl, ethyl, n-propyl,
Aliphatic groups such as isopropyl and butyl.

There are no particular restrictions on the alcohol, but preferably,
It is an aliphatic alcohol of groups such as methyl, ethyl, n-propyl, isopropyl, butyl.

The amount of 7/L/cole used is 1 to 10 times, preferably 2 to 5 times, in molar ratio to monochloroacetic ester.

Carbon monoxide does not need to be particularly pure, and carbon monoxide containing hydrogen and an inert gas may be used.

Furthermore, in addition to alcohol, insoluble solvents such as aliphatic, aromatic hydrocarbons, pyridine, picoline, and esters of organic acids may be present.

With regard to water in the reaction system, the method of the present invention reduces reactivity (
There is no effect on reaction rate, catalytic activity), but
Since malonic acid monoester is produced by reacting with water, when producing malonic acid diester, it is preferable to keep the initial moisture concentration within 1% by weight.

More preferably, the amount of water is 0.1 to 0.8% by weight, and if malonic acid monoester is co-produced, there is no problem even if there is more water than that.

The yields are about the same in either case. The reaction temperature was 30
~100°C, preferably 40=70°C.

The reaction pressure is 2 to 50 kg/cd, preferably 5 to 3
0 kg/cm.

The present inventor has already published Japanese Patent Application No. 53-98254 (Japanese Unexamined Patent Publication No. 55-2701) regarding a method for producing a Co (CO)4 solution.
5), Japanese Patent Application No. 53-99389 (Japanese Patent Application No. 55-27845)
), Japanese Patent Application No. 53-127686 (Japanese Patent Application No. 55-540)
38) and special application 1973-! 27687 (Unexamined Japanese Patent Publication No. 1987-
56020).

According to these, it is obtained by reacting a cobalt compound (for example, a hydrate or anhydride of cobalt hydroxide, cobalt carbonate, cobalt acetate, etc.) with carbon oxide and hydrogen in a solvent such as alcohol or acetone.

Furthermore, if a Cτ(CO)4 solution is used as a seed catalyst, the conditions are significantly relaxed and production can be performed at low temperature and low pressure.

Furthermore, in the case of Co2 (CO")B, in a polar solvent such as alcohol or acetone, the disproportionation reaction according to the reaction formula proceeds completely in the case of alcohol, as reported in the Journal of the American Chemical Society ( 74, p. 1216), a catalyst prepared using this reaction can also be used in the present invention.

Next, the present invention will be further explained with reference to Examples.

In addition, in the examples, % indicates mol%.

Example 1 In an autoclave with a capacity of 21 and equipped with a pressure-resistant pH meter, isopropyl fluid T-/L/380? , Co (Co
)4 acetone solution 83cc (Co (Co)410P
), and Na2CO3108 as a basic substance? , N
Charge 2 g of aOH into the reaction vessel.

The inside of the reactor was replaced with carbon monoxide, - carbon oxide pressure 7 kg/
2 moles of isopropyl monochloroacetate are added in portions over a period of 3 hours at a cm temperature of 60°C.

Then age for 2 hours.

During this time, carbon oxide was passed through at a rate of 20 J/hr.

Table 1 shows the change in pH over time during the reaction.

After the reaction, the pressure was returned to normal and analyzed by gas chromatography, the reaction rate of isopropyl monochloroacetate was 98.5.
%, and the selectivity of diisopropyl malonate is 95.5%.
, the selectivity of monoisopropyl malonate was 2.1%.

The reaction rate at the end of the fractional addition was 71%.

The catalyst liquid used was prepared by using an acetone solution of Co (CO)4 as a seed catalyst and cobalt hydroxide with carbon monoxide and hydrogen at 10 kg/cn7L at 80°C.

Comparative Example 1 This was the same as in Example 1, except that all the raw materials were charged at once and the reaction was carried out.

After 5 hours of reaction, analysis revealed that the reaction rate was 63%.

Also, the change in pH over time during the reaction was as shown in Table 2.

Example 2 Same as Example 1, but using Co2 (CO)8 12F as a catalyst and adding 2 to the basic substance.
CO3147P and KOH3,5P were used.

After reacting in the same manner for 5 hours, analysis revealed that the reaction rate of isopropyl monochloroacetate was 94%, the selectivity of diisopropyl malonate was 94.5%, and the selectivity of monoisopropyl malonate was 1.8%. Met.

When the change in pH was observed over time, it was the same as in Example 1.

Also, at the end of the fractional addition of isopropyl monochloroacetate,
The reaction rate was 67%.

Example 3 Same as Example 2, but adding water into the initial reaction system,
When the amount was adjusted to 0.65 wt%, the reaction rate at the end of the fractional addition of isopropyl monochloroacetate was 65%.
Met.

Further, after the reaction was completed, analysis revealed that the reaction rate of inpropyl monochloroacetate was 94.6%, the selectivity of diisopropyl malonate was 93.9%, and the selectivity of monoisopropyl malonate was 1.9%. Met.

Example 4 Same as Example 1, but - carbon oxide pressure 7 kg/c.

When the partial pressure of carbon dioxide gas in the reactor reached 50%, purge was started, and after that, purging was continued to maintain the partial pressure of carbon dioxide gas at 40 to 50%, and the reaction was continued for 5 hours. Ta.

As a result of the analysis, the results were similar to those in Example 1, and the change in pH over time was also the same.

Example 5 Same as Example 1, but with methanol 320S', 63 cc of methanol solution of 0 Co (Co)
49.5r containing top and Na2CO3110PSKOH2
, 31 was used.

- At a carbon oxide pressure of 6 kg/crri and a temperature of 55°C, methyl monochloroacetate was added in portions over 4 hours, and then aged for 1 hour.

During this time, -carbon oxide was passed at a rate of 151/hr.

As a result of analysis, the reaction rate of methyl monochloroacetate was 97.
The selectivity for dimethyl malonate was 96%.

Changes in pH over time were automatically controlled in the same manner as in Example 1.

The catalyst used was a methanol solution of Co(CO)4 produced by reacting cobalt acetate anhydride (co(CH3COO)2) with carbon monoxide and hydrogen in methanol as a seed catalyst, and cobalt acetate anhydride was used as a seed catalyst. It was produced by reacting with carbon oxide and hydrogen at 25 kg/crA and 120°C.

Comparative Example 2 Same as Example 2, but using 2CO31 as the basic substance.
51fI' was used.

The change in pH during the reaction is as shown in Table 3, and the reaction rate after 5 hours was 76%, and the selectivity of diisopropyl malonate was 87%.

Example 6 400 g of ethanol and Co2(CO)815Si' were charged into an autoclave, and after complete disproportionation, Na2C
O3107? The same procedure as in Example 1 was carried out except that ethyl monochloroacetate was used instead of isopropyl monochloroacetate and KOH2,3P was charged.

After the reaction, analysis showed that the reaction rate of monochloroethyl acetate was 9.
At 5.6%, the selectivity for diethyl malonate was 94.8%.

Claims (1)

[Claims] 1 In the presence of a cobalt carbonyl catalyst, monochloroacetate is reacted with carbon monoxide, alcohol, and a basic substance to produce malonic acid diester. Hydroxide is used, and the ratio is 9 by weight.
5.0 to 99.5: 5.0 to 0.5, and the amount used is such that the basic substance is present in a stoichiometric amount or more with respect to the total amount of monochloroacetic ester, and monochloroacetic ester is added in portions. A method for producing malonic acid diester characterized by: