JPS5917100B2 - 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 monochloroacetic ester with carbon monoxide, alcohol and a basic substance in the presence of a cobalt carbonyl catalyst. This invention relates to a method for producing malonic acid diester in which basic substances are mixed in a specific ratio and a cobalt carbonyl catalyst is added in portions.

Malonic acid diester is an important product as an intermediate for pharmaceuticals and agricultural chemicals, and organic halides are mixed with carbon monoxide and alcohol in the presence of a salt of cobalt tetracarbonyl anion (hereinafter referred to as Co(Co)4). The production of esters of organic acids by reacting with basic substances and
No. 0-10967 discloses that monochloroacetic ester is also used as this raw material, but it has the drawback of low yield.

As a result of various studies on the causes of this, we found that the influence of catalytic activity and basic substances is large, and that alkali metal carbonates and/or bicarbonates are preferable in terms of reaction and cost. It is not enough to simply use a catalyst, but there is a need for an improved production method that suppresses the phenomenon of pH decrease in the initial stage of the reaction and prevents catalyst deactivation. In order to solve these drawbacks, the present invention specifies the type, proportion, and amount of the basic substance when reacting monoc'5-rolacetate, carbon monoxide, alcohol, and a basic substance in the presence of a cobalt carbonyl catalyst. Furthermore, by improving the method of adding the cobalt carbonyl catalyst, the pH is automatically controlled to 0, and the reaction proceeds without any problems with catalyst activity, resulting in stable operation and high yields. The present invention aims to provide a method for producing malonic acid diester. As the basic substance used in the present invention, the following two types, A5 base and B base, are used in combination.

The A base is an alkali metal carbonate and/or bicarbonate, preferably Na2co3, 2CO3, :5-N
aHCO3 and KHCO3.

Base B is an alkali metal hydroxide.

As the alkali metal hydroxide, NaOH. KOH is preferred. The basic substance should be used in a stoichiometric amount or more, 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 amount is used in a ratio of 0.5 to 5% by weight of the sum of A base and B base.

Base B is a desirable base for improving yield, but
When used alone, side reactions easily proceed, making it virtually impossible to charge them all at once. Therefore, it is necessary to dissolve it in a solvent and add it to the reaction system in small portions.
There were problems with the dissolution operation, pH control, decreased productivity, and reproducibility, but by using it in combination with A base, batch addition becomes possible and good selectivity can be obtained. The reaction method is to charge the monochloroacetic ester, alcohol, and basic substance all at once, and then add the cobalt carbonyl catalyst in portions.

If the entire amount of the catalyst used is initially charged, it will be difficult to use the catalyst efficiently, a stable pH will not be obtained, problems will arise in temperature control due to heat generation, and a decline in reaction performance will be inevitable. The most desirable method is to continuously drop the cobalt carbonyl catalyst solution little by little over a period of about 1/2 of the total reaction time, but it is also possible to add the entire catalyst in several portions. . Alternatively, 1/400 mol or less, preferably 1/100 mol or less of monochloroacetic ester at the start of the reaction.
It is also possible to add less than a molar amount of cobalt carbonyl catalyst, then add it little by little as the reaction progresses, and continue the reaction for 1 to 2 hours after the addition is complete. Preferred cobalt carbonyl catalysts used in the present invention include dicobalt octacarbonyl (hereinafter referred to as CO2CO)8 and cobalt tetracarbonyl anion (hereinafter referred to as Cd(CO)4). The preferred catalyst used in the present invention is Cd(CO)4, and since the catalyst is added in portions, it is preferably in the form of a solution. As the solvent, it is preferable to use alcohols, ketones such as acetone, ethers, and mixtures thereof as main solvents, but in addition to these, hydrocarbons, esters, lower fatty acids, pyridine, water, etc. may be mixed. Other solvents can also be used. Regarding the manufacturing method of C8(CO)4 solution, the present inventor has already published Japanese Patent Application No. 53-9825.
4 (Japanese Unexamined Patent Publication No. 55-27015), Patent Application No. 53-9
9389 (Japanese Unexamined Patent Publication No. 55-27845), patent application 1977
3-127686 (Japanese Unexamined Patent Publication No. 55-54038) and Japanese Patent Application No. 53-127687 (Japanese Patent Publication No. 57-32007).

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 monoxide and hydrogen in a solvent such as alcohol or acetone. Furthermore, CO
If a (CO)4 solution is used as a seed catalyst, the conditions will be significantly relaxed and production can be performed at lower temperatures and pressures than in the past. Also, CO2 (
Journal of the American Chemical Society (Vol. 74, p. 1216) shows that in polar solvents such as alcohol and acetone, the disproportionation reaction of CO)8 proceeds completely according to the reaction formula. ), catalysts prepared using this reaction can also be used in the present invention.

CO2(CO)8 can be used in the presence of benzene or toluene. Furthermore, in addition to alcohol, insoluble solvents such as aliphatic, aromatic hydrocarbons, pyridine,
Picoline and an ester of an organic acid may coexist. The molar ratio of the cobalt carbonyl catalyst to the monochloroacetic ester is 1:1 to 1:4001, preferably 1:4 to 1.
:100. The ester moiety of monochloroacetic ester is not particularly limited, but is preferably an aliphatic group such as methyl, ethyl, n-propyl, 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 molar ratio of alcohol and monochloroacetic ester is 1 to
It is 10 times the mole, preferably 2 to 5 times the mole. Carbon monoxide does not need to be particularly pure, and carbon monoxide containing hydrogen and an inert gas may be used.

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 that the initial moisture concentration is within 1% by weight of the monochloroacetic ester. More preferably, the moisture content is within 0.8% by weight, and if malonic acid monoester is co-produced, there is no problem even if the moisture content is higher than that. The reaction temperature is 30~
The temperature is 100°C, preferably 40-70°C.

The reaction pressure is 2-501<9/CTl, preferably 5-3
01<9/0d. The present invention will be specifically explained below with reference to Examples.

Note that in the examples, % indicates mol%. Example 1 In an autoclave with a capacity of 21 and equipped with a pressure-resistant PH meter, 2 moles of isopropyl monochloroacetate and 3 moles of isopropyl alcohol were added.
60y and Na2CO3lO6y, .
NaOH27 was charged all at once.

The inside of the reaction vessel was replaced with carbon monoxide, and the carbon monoxide pressure was reduced to 8k9.
/CTilLl At a temperature of 63° C., 95 ml of an acetone solution of CO(CO)4 (containing 10y of CO(CO)4) was continuously added using a pump over a period of 3 hours.

It was then aged for 3 hours. During this period, carbon monoxide was 20j/h.
It circulated at a rate of r. Table 1 shows the change in pH over time during the reaction.

As a result of analysis, the reaction rate of monochloroisopropyl acetate was 98.7%, and the selectivity of diisopropyl malonate was 98.7%.
4.7%, selectivity for monoisopropyl malonate is 2.6
It was %.

The reaction rate at the end of the fractional addition was 65%.

The catalyst solution used was an acetone solution of CO(CO)4 as a seed catalyst, and cobalt hydroxide was mixed with carbon monoxide and hydrogen.
It was obtained by reacting at 0 kg/C7lll80°C. Comparative Example 1 A reaction was carried out in the same manner as in Example 1, except that the catalyst solution and other raw materials were charged all at once at the start of the reaction.

As a result of analysis after 6 hours of reaction, the reaction rate was 67%.

Example 2 CO2 (CO) 8157 as a catalyst and acetone 300f
The reaction was carried out in the same manner as in Example 1, except that a completely disproportionated solution was used at room temperature, and 477 liters of K2CO3 and 3.57 liters of KOH were used as the basic substances.

After reacting for 6 hours, analysis revealed that the reaction rate of isopropyl monochloroacetate was 96.7%, the selectivity of diisopropyl malonate was 95.2%, and the selectivity of monoisopropyl malonate was 1.9%. Ta.

The reaction rate at the end of the fractional addition of isopropyl monochloroacetate was 68%. Example 3 105 ml of an acetone solution of Cd(CO)4 as a catalyst (
The reaction was carried out at a carbon monoxide pressure of 8 k9/d, and the partial pressure of carbon dioxide in the reactor was 4 kg/C! The reaction was carried out in the same manner as in Example 1, except that purging was started when the temperature reached 11, and thereafter purging was continued to maintain the carbon dioxide gas partial pressure at 3 to 4 kg/CIi.

The results of the analysis were almost the same as in Example 1. The catalyst solution used was acetone solution of CO(CO)4 produced in the same manner as the catalyst solution used in Example 2 as a seed catalyst, and cobalt acetate anhydride was mixed with carbon monoxide and hydrogen at 20 kg/Cri.
1, obtained by reaction at 110°C. Comparative Example 2 A reaction was carried out in the same manner as in Example 2 except that only base A, K2CO3l5O7, was used as the basic substance.

The reaction rate after 6 hours was 72%, malonic acid dicomparative example 3 K2CO3l49.47 and KOHO. 6
The reaction was carried out in the same manner as in Example 2 except that t was used.

The reaction rate after 6 hours was 74%, and the selectivity for diisopropyl malonate was 82%.

Comparative example 4 K2CO3l4l7 and KOH9f7 as basic substances
The reaction was carried out in the same manner as in Example 2 except that .

After 6 hours, the reaction rate was 98%, and the selectivity for diisopropyl malonate was 78%.

Example 4 A reaction was carried out in the same manner as in Example 1, except that 200 ml of a toluene solution of CO2(CO)8 (containing 815? of CO2(CO)) was used as the catalyst.

As a result of post-reaction analysis, the reaction rate of isopropyl monochloroacetate was 96.3%, and the selectivity of isopropyl malonate was 94.
．． It was 0%. Example 5 A reaction was carried out in the same manner as in Example 2, except that C02(CO)8 was replaced with acetone 300V and complete disproportionation was performed with a mixed solution of acetone 1507 and pyridine 20f7.

As a result of post-reaction analysis, the reaction rate of isopropyl monochloroacetate was 96.6%, and the selectivity of diisopropyl malonate was 9.
It was 5%. Example 6 Using CO2 (CO)8157 as a catalyst with acetonitrile2
The reaction was carried out in the same manner as in Example 2, except that a completely disproportionated solution in 00f7 was used.

As a result of post-reaction analysis, the reaction rate of isopropyl monochloroacetate was 94.8%, and the selectivity of diisopropyl malonate was 9.
It was 2.7%. Example 7 NaHCO3l68VlNaOH2 as a basic substance
The reaction was carried out in the same manner as in Example 1, except that 7 was used.

As a result of post-reaction analysis, the reaction rate of isopropyl monochloroacetate was 96.8%, and the selectivity of diisopropyl malonate was 93.9%.

Claims (1)

[Claims] 1. In producing malonic acid diester by reacting monochloroacetate, carbon monoxide, alcohol and a basic substance in the presence of a cobalt carbonyl catalyst, A base: an alkali metal carbonate and/or
Alternatively, bicarbonate and B base: alkaline metal hydroxide are used in a ratio such that B base is 0.5 to 5% by weight of the sum of A base and B base, and a cobalt carbonyl catalyst is added in portions. A method for producing malonic acid diester characterized by the following.