JPS6045627B2 - Production method of malonic acid dialkyl ester - Google Patents

Description

[Detailed description of the invention] The present invention relates to a method for producing malonic acid dialkyl esters.

More particularly, the present invention relates to a process for the preparation of malonic acid dialkyl esters, characterized in that dihalogenated methane, carbon monoxide and alcohol are reacted in the presence of a cobalt carbonyl complex and a basic agent. According to the present invention, a symmetric dialkyl malonic acid ester can be produced in one step and the yield is extremely good, so that it is useful as a method for producing the malonic acid ester on an industrial scale.

The following method is already known as a method for producing malonic acid dialkyl ester.

(a) A method of reacting chloroacetic acid with an alkali cyanide to synthesize cyanoacetic acid, saponifying the nitrile, and then esterifying it (Ullmann, 12, 192 (1960)).

(b) A method in which potassium acetate is reacted with carbon monoxide (Japanese Patent Publication No. 46-26926) or carbon dioxide (Japanese Patent Publication No. 46-28523) in the presence of potassium carbonate to synthesize potassium malonate salt, which is then esterified.

(c) A method in which acetic acid ester is reacted with carbon dioxide in the presence of an alkali metal alcoholate to synthesize malonic acid monoester and then esterified (Japanese Patent Application Laid-Open No. 49-3661 Wani).

(d) A method for synthesizing malonic acid dialkyl ester by reacting halogenated acetic acid alkyl ester in the presence of a catalyst containing carbon monoxide and a cobalt compound (Japanese Unexamined Patent Application Publication No. 1989-1983)
-111015, 51-146414).

All known methods disclose methods for utilizing the carbonyl group of an acetic acid derivative as one of the carbonyl groups of malonic acid and introducing the other one.

In contrast, the method of the present invention provides a one-step synthesis method of malonic acid ester in which two carbonyl groups are supplied by insertion of carbon monoxide and esterification is performed simultaneously without using an acetic acid derivative. It is something.

The method of the present invention utilizes a reaction that can be represented diagrammatically as shown below.

(In the formula, R is an alkyl group, and The reaction may be carried out in the presence of a sex-active substance.

Although this reaction proceeds under normal pressure, it is not very practical to carry out on an industrial scale, and for reasons such as effective use of carbon monoxide, it is convenient to carry out the reaction under closed pressure. The degree of pressure is 20
~9 mutter pressure is suitable. The reaction temperature is 70-140°C, preferably 100-120°C.

The alcohol is preferably a lower alcohol such as methanol, ethanol, propanol, isopropanol, n-butanol.

This alcohol can also act as a solvent. Of course, inert solvents such as aliphatic or cyclic ethers, ketones, and esters can also be used as solvents. However, since this reaction is usually carried out in a suspended state, it is desirable to use an appropriate solvent to facilitate the reaction. As basic active substances,
Suitable examples include alkali metal and alkaline earth metal carbonates, bicarbonates, acetates, hydroxides, oxides, alcoholates, and tertiary amines such as pyridine.

Theoretically, the amount of basic active substances used is 2 mol for monoacid basic active substances and 1 mol for diacid basic active substances per 1 mol of dihalogenated methane, but it is recommended to use a slightly excessive amount. There is no problem.

The cobalt carbonyl complex may be selected from cobalt carbonyl•phosphine complexes and cobalt carbonyl•pyridine complexes. Such a complex may be generated within the reaction system, or may be prepared separately outside the reaction system.
For example, in the former case, a catalytic amount of phosphine or pyridine to form a complex with cobalt carbonyl, ie, octacarbonyl dicobalt CO2 (CO)8, is present in the system and the reaction of the present invention is allowed to proceed at the same time.
The phosphine to form a complex with cobalt carbonyl is preferably a tri-substituted phosphine, including, for example, triphenylphosphine and trialkylphosphine. Therefore, a typical example of a cobalt carbonyl phosphine complex is CO2(CO)6(PX
3) Complexes represented by the formula 2 (wherein X represents an aryl group or an alkyl group), examples of which include the following. Hexacarbonyl dicobalt Bis(triphenylphosphine) complex Hexacarbonyl dicobalt Bis(
The following formula is given for the tri-n-butylphosphine) complex hexacarbonyl dicobalt●bis(tri-n-octylphosphine) complex cobalt carbonyl●pyridine complex.

The amount of cobalt carbonyl complex to be used may be a catalytic amount, and is 1'5 to 1120% per mole of dihalogenated methane.
It may be determined as appropriate from the range of 0 mol, preferably from 1110 to 1120 mol.

Therefore, when forming a complex in the system, the amount of cobalt carbonyl and phosphine or pyridine to be added should be adjusted so as to obtain the above-mentioned catalytic amount.
The cobalt carbonyl complex can be recovered after the reaction is completed, and the recovered complex can be reused as it is or after washing with dilute sulfuric acid, for example.

By the way, in theory, the usage ratio of various raw material components in the method of the present invention is 2 moles of carbon monoxide and alcohol per 1 mole of dihalogenated methane, but in order to make the reaction proceed smoothly, It is preferable to use carbon monoxide in a slight excess to 8 moles of the theoretical amount and alcohol in 3 to 16 moles per mole of dihalogenated methane.

Dihalogenated methane includes dichloromethane, diprommethane, and bromochloromethane.

Among them, dichloromethane can be used advantageously because it is available at low cost. Therefore, to carry out the process of the invention, taking into account the various explanations given above, carbon monoxide must be forced into a solution or suspension containing the other reactants and the catalyst and the base. That's fine, but...
Reactants, catalysts, or bases are placed in an autoclave in advance in a well-balanced combination, and the remaining reactants,
Carbon monoxide may be passed before or after or simultaneously with the addition of the catalyst or base.

Even if the catalyst is produced in the reaction system, the basic operations remain the same. Incidentally, carbon monoxide may be used in a diluted form with an inert gas. The reaction time depends on the degree of pressurization,
Although it varies depending on the type of reactant and other factors, it is sufficient to react for 6 to 2 hours. After the reaction is completed, the reaction mixture is cooled, water is added to the reaction mixture, acidified with a suitable acid such as sulfuric acid, extracted with a solvent, and after drying, the solvent is distilled off to obtain the desired malonic acid dialkyl ester in a good yield. I can do it.

The method of the present invention not only allows malonic acid dialkyl ester to be obtained in a good yield in one step, but also enables the catalyst to be obtained at a rate of 90%.
% or more can be recovered as a complex, and it can be reused with no reduction in catalytic ability, so it can be advantageously applied to cyclical production.

Furthermore, according to the method of the present invention, dichloromethane or dipromemethane can be used as raw materials, and the selection of raw materials is more restricted than in the method of simply using cobalt carbonyl as a catalyst. This is extremely advantageous. Example 1 Synthesis of malonic acid dimethyl ester 10 ml of dichloromethane was placed in an autoclave with an internal volume of 130 m1.
．． 2g (0.12 mol), pyridine 12.6g (0.1
6 mol), methanol 20.5 g (0.64 mol), cobalt carbonyl CO2 (CO) 82.7 g (0.00
8 mol), triphenylphosphine 4.2 g (4). 0
16 mol) and 45 atm (0.16 mol) of carbon monoxide were charged and a two-bridge reaction was carried out at 120° C. with stirring.

After the reaction is complete, water is added, acidified with sulfuric acid, and extracted with ether. After drying over anhydrous sodium sulfate, the solvent was distilled off to obtain 2.1 g (purity 66.7%) of dimethyl malonate. The yield of the malonic acid ester produced was 72.2% based on the dichloromethane consumed in the reaction. (Note) In this example, a large amount of dichloromethane was used.

Example 2 Synthesis internal volume of malonic acid diethyl ester 50
18.7 g of dichloromethane (
0.22 mol), sodium carbonate 19.3 g (0.14
mol), ethanol 157.8g (3.43 mol), cobalt carbonyl 3. ．． 4g (a). 01 mol), triphenylphosphine 6.6 g (0.025 mol), carbon monoxide 85 atm (a). 95 mol) and reacted for two cells at 70°C to 135°C with stirring.

After completion of the reaction, 6.7 g (purity of 61.2%) of malonic acid diethyl ester is obtained by post-treatment according to Example 1. Yield 53.2% (based on dichloromethane consumption). Example 3 Synthesis Example 1 of malonic acid di-n-propyl ester
6.4 g of dichloromethane (a). 075 mol),
Potassium hydroxide 5.6 g (0.1 mol), propanol 18.0 g (0.3 mol), cobalt carbonyl 1.7
g (0.005 mol), triphenylphosphine 2.6
g(4). 01 mole), carbon monoxide 47 atm (a). 1
3.7 g (purity 67.6%) of malonic acid di-n-propyl ester was obtained by performing a two-dish reaction at 120°C using
I got it.

Yield 65.3% (based on dichloromethane consumption). Example 4
Synthesis of malonic acid diisopropyl ester According to Example 1, dichloromethane 4.3 g (0.05 mol), potassium carbonate 6.9 g (0.05 mol), isopropanol 18.0 g (0.3 mol), cobalt carbonyl 1.
7 g (0.005 mol), triphenylphosphine 2.
6g (0.01 mol), carbon monoxide (a) atmospheric pressure (0.3
6 mol) at 120° C. to obtain 3.2 g (purity: 68.8%) of diisopropyl malonate.

Yield 66.7% (based on dichloromethane consumption). Example 5
~7 Synthesis of malonic acid diisopropyl ester using a recovered catalyst Performed using 4.1 g (0.005 mol) of hexacarbonyl dicobalt bis(triphenylphosphine) complex recovered after the synthesis of Example 4 and washed with dilute sulfuric acid. Synthesis experiments were repeated five times according to Example 1, and the reusability of the catalyst was examined.

Example 8 Synthesis of malonic acid isopropyl ester Example 1
Dipromemethane 8.6 g (0.05 mol), potassium carbonate 6.9 g (0.05 mol), isopropanol 18.0 g (0.3 mol), cobalt carbonyl 1.7
g (0.005 mol), triphenylphosphine 2.6
g (0.01 mol) and carbon monoxide at 41 atm (0.14 mol) at 120° C. for 2 hours to obtain 4.1 g (purity 65.9%) of diisopropyl malonate.

Yield 78.0% (based on dipromemethane consumption). Example 9
Synthesis of malonic acid diisopropyl ester According to Example 1, 9.8 g of bromochloromethane (a). 075
mole), potassium carbonate 6.9g (a). 05 mol), isopropanol 18.0 g (0.3 mol), recovered hexacarbonyl dicobalt bis(triphenylphosphine) complex 4.1 g (0.005 mol), carbon monoxide 5 direct pressure (a). 26 mol) at 100° C. to obtain 5.8 g (purity: 60.3%) of diisopropyl malonate.

Yield 68.6% (based on bromochloromethane consumption). still,
Instead of the recovered catalyst, unused hexacarbonyl dicobalt bis(triphenylphosphine) was synthesized separately outside the system.
Using the complex, operate in the same manner as above to obtain 4.5g of the target product.
(purity 66.7%) was obtained.

Yield 73.5% (based on bromochloromethane consumption). Example 10 Synthesis of malonic acid di-n-butyl ester Dichloromethane 6.4 g (0.075 mol), potassium carbonate 6.9 g (0.05 mol), n-butanol 18.5 g (0.25 mol) mole), cobalt carbonyl 1.7 g (4). 005 mol), tri-n-butylphosphine 2.0 g (a). 01 mole), carbon monoxide 48 atm (a). 2 mol) was reacted at 120°C for 2 hours to obtain 3.8 g (
Purity of 48.2%) was obtained.

Claims (1)

[Claims] 1. A process characterized by reacting dihalogenated methane, carbon monoxide and alcohol in the presence of a cobalt carbonyl complex selected from a cobalt carbonyl phosphine complex or a cobalt carbonyl pyridine complex and a basic acting substance. Method for producing malonic acid dialkyl ester. 2. The production method according to claim 1, wherein the dihalogenated methane is dichloromethane, dibromomethane, or bromochloromethane. 3. The manufacturing method according to claim 1, wherein the alcohol is a lower alcohol. 4 The cobalt carbonyl phosphine complex is a hexacarbonyl dicobalt bis(triphenylphosphine) complex, a hexacarbonyl dicobalt bis(tri-n-butylphosphine) complex, or a hexacarbonyl dicobalt bis(tri-n-octylphosphine) complex. The manufacturing method according to claim 1, which is a complex. 5 Cobalt carbonyl pyridine complex is nonacarbonyl tricobalt pentapyridine Co_3(CO)_9
- (Py)_5 (Py represents pyridine) The manufacturing method according to claim 1. 6. The production method according to claim 1, which comprises reacting in the presence of a cobalt carbonyl complex synthesized in a reaction system. 7. The process according to claim 1, wherein the basic acting substance is an alkali metal or alkaline earth metal carbonate, bicarbonate, acetate, hydroxide, oxide or alcoholade or amine. 8. The manufacturing method according to claim 1, which comprises using slightly more carbon monoxide and alcohol than the theoretical amount. 9. The method according to claim 1, which comprises using a catalytic amount of a cobalt carbonyl complex. 10. The production method according to claim 9, wherein the amount of cobalt carbonyl complex used is 1/5 to 1/200 mol per 1 mol of dihalogenated methane. 11. The method according to claim 10, wherein the amount of cobalt carbonyl complex used is preferably 1/10 to 1/20 mole per mole of dihalogenated methane. 12. The manufacturing method according to claim 1, which comprises reacting under sealed pressure. 13. The manufacturing method according to claim 12, which comprises reacting under 20 to 90 atmospheres.