JPH05306261A - Production of dicarbonic acid dialkyl ester - Google Patents

Abstract

PURPOSE:To produce the subject high-purity dicarbonic acid dialkyl ester in a high yield. CONSTITUTION:An alkaline metal salt of a carbonic acid alkyl ester, e.g. sodium t-butyl carbonate is reacted with an acid halide compound e.g. tosyl chloride and the resultant dicarbonic acid dialkyl ester, e.g. dicarbonic acid di-t-butyl ester is water-washed till water after used for washing exhibits a pH value within a range of 4.5 to 7.0 and an electrical conductivity value within a range of the value before used for washing to 200muS. The water-washed compound is then distilled.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for industrially producing dialkyl dicarbonic acid esters.

[0002]

Dialkyl dicarbonates are important compounds as amino group protecting agents for amino acids in peptide chemistry. Conventionally, as a method for synthesizing a dialkyl dicarbonate, a method of reacting an alkali metal carbonate of an alkyl carbonate with an acid halide is known. The reaction mixture obtained by the reaction contains fine crystals of by-product salts. Therefore, as a means for removing these by-product salts, a method of washing with water (Czechoslovak Patent No. 257,157) is usually adopted. And
After that, the desired dicarbonic acid dialkyl ester was obtained by distillation.

[0003]

The inventors of the present invention additionally tried the above technique in order to synthesize a dialkyl dicarbonate in a good yield. As a result, the dialkyl dicarbonate produced was decomposed by distillation and a sufficient yield was obtained. Therefore, dialkyl dicarbonate could not be obtained.

[0004]

Means for Solving the Problems As a result of diligent studies of a method for industrially advantageously carrying out distillation purification of dicarbonic acid dialkyl ester, the present inventors have found that the dicarbonic acid dialkyl ester was washed with water before distillation and after washing with water. It was found that the pH of the water layer in Example 1 was biased to the acidic side, and the electric conductivity of the water layer after washing showed a very high value. Based on this finding, by performing water washing until the pH and electric conductivity of the water layer after washing reach a specific range, it is possible to suppress decomposition of dialkyl dicarbonate ester by distillation to a low level and significantly improve the distillation yield. The present invention has been completed and the present invention has been completed.

That is, the pH of the water after the dicarbonic acid dialkyl ester obtained by reacting the carbonic acid alkyl ester alkali metal salt and the acid halide with each other is 4.5 to
A method for producing a dialkyl dicarbonate ester is characterized in that it is washed with water until the electric conductivity is 7.0 and the electric conductivity of water before use becomes ˜200 μS and then distilled.

In the present invention, the reaction liquid used for washing with water is obtained by reacting an alkali metal carbonate of carbonic acid with an acid halide. As the carbonic acid alkyl ester alkali metal salt, sodium t-butyl carbonate,
Potassium t-butyl carbonate, sodium propyl carbonate,
Examples thereof include sodium ethyl carbonate and sodium methyl carbonate.

Carbonic acid alkyl ester alkali metal salt is
It can be obtained by reacting the corresponding alkali metal alkoxide with carbon dioxide, but it may be isolated by a known method after the reaction, or in some cases, it may be used in the above reaction without isolation.

As the acid halide in the present invention, known ones may be used without any limitation, but aromatic sulfonyl halides are preferably used since they yield the target compound in high yield. As the aromatic sulfonyl halide, a known compound having a halogenosulfone group bonded to an aromatic ring is used without any limitation. In particular, in the present invention, the following formula

[0009]

[Chemical 1]

An aromatic sulfonyl halide represented by the formula (wherein R ¹ and R ² are a hydrogen atom, a halogen atom or an alkyl group, and X is a halogen atom) is preferably used.

Specific examples of aromatic sulfonyl halides that can be preferably used in the present invention are as follows. Benzenesulfonyl chloride, p-toluenesulfonyl chloride, 2,4-dimethylbenzenesulfonyl chloride, p-chlorobenzenesulfonyl chloride, 2,4-dichlorobenzenesulfonyl chloride, benzenesulfonyl bromide, p-toluenesulfonyl bromide, p-chlorobenzenesulfonyl bromide, etc. Can be mentioned.

The amount of the acid halide with respect to the above-mentioned alkali metal carbonate of alkali metal carbonate is usually 1 mol of the alkali metal carbonate of alkyl carbonate because one molecule of dialkyl dicarbonate is produced from 2 molecules of alkali metal carbonate of alkyl carbonate. Is selected in the range of 0.3 to 0.5 mol.

In the above reaction, it is preferable to use a catalyst to promote the reaction. Any known catalyst can be used without any limitation, but an aliphatic tertiary amine or an aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom through an alkylene group gives a target compound in high yield, It is preferably used. In particular, in the present invention, the following formula

[0014]

[Chemical 2]

(Wherein R ³ and R ⁴ are the same or different alkyl groups, R ⁵ is an alkylene group, Y is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group, or

[0016]

[Chemical 3]

(Wherein R ⁶ and R ⁷ are a hydrogen atom or an alkyl group, at least one is an alkyl group, and Z is O, S or> N—R ⁸ (wherein R ⁸ is a hydrogen atom or an alkyl group). A group), n is an integer of 1 or more, and m is 0 or 1.).

Aliphatic 3 which can be preferably used in the present invention
Specific examples of primary amines or aromatic tertiary amines having an aromatic ring bonded to a nitrogen atom via an alkylene group include:
Trimethylamine, N, N-dimethylbenzylamine,
N, N-diethylbenzylamine, N, N, N ', N'
-Tetramethylethylenediamine, N, N, N'N'-
Tetramethyl-1,3-propanediamine, N, N,
N'N'-tetramethyl-1,6-hexanediamine,
N, N, N'N'-tetraethyl-1,3-propanediamine, N, N, N'N'-tetraethyl-1,6-hexanediamine, N, N, N'N'-tetramethyl-
1,4-butanediamine, N, N, N'N'-tetramethyl-1,3-butanediamine, bis- [2- (N, N
-Dimethylamino) ethyl] ether, bis- [2-
(N, N-dimethylamino) propyl] ether, bis- [2- (N, N-dimethylamino) ethyl] sulfide, bis- [2- (N, N-dimethylamino) propyl]
Sulfide, 2- (N, N-dimethylamino) ethyl ethyl ether, 2- (N, N-dimethylamino) ethyl ethyl sulfide, bis- [2- (N, N-dimethylamino) ethyl] methylamine and the like. be able to.

Among the aromatic tertiary amines represented by the above general formula or aromatic tertiary amines having an aromatic ring bonded to a nitrogen atom via an alkylene group, Y is an aryl group or

[0020]

[Chemical 4]

(Where R ⁶ and R ⁷ are hydrogen atoms or alkyl groups, at least one of which is an alkyl group), the yield of the target compound is particularly high. It is preferably used in the invention.

The amount of the above-mentioned aliphatic tertiary amine or aromatic tertiary amine in which an aromatic ring is bound to a nitrogen atom via an alkylene group is not particularly limited, but in order to obtain a sufficient reaction rate. In addition, 0.01 to 20 mol%, and further 0.0
It is preferably in the range of 5 to 10 mol%.

In this reaction, in order to improve the dispersibility of the reaction solution, the concentration of the alkali metal carbonate carbonate is 3 to
It is desirable to dilute with a solvent so as to be 60% by weight. The solvent used in this reaction is not particularly limited, and aromatic hydrocarbons such as benzene, toluene and xylene;
Ethers such as 4-dioxane and tetrahydrofuran;
Acetonitrile, methylpyrrolidone, N, N-dimethylformamide and the like are used. Further, an alcohol corresponding to the alkyl group in the starting material alkyl carbonate alkali metal salt can also be used. These organic solvents may be used alone or may be used as a mixed solvent of two or more kinds at all.

The reaction temperature in this reaction is not particularly limited, but if the temperature is too low, the reaction rate becomes small, and if the temperature is too high, the starting material and the target compound are decomposed, so that it is usually 0 to 100 ° C., preferably 20 to 80. It is preferable to carry out at ° C.

The reaction can be carried out under any of normal pressure, increased pressure and reduced pressure, and it is particularly preferable to carry out the reaction under increased pressure of carbon dioxide gas in order to obtain a target compound in high yield. Although the time required for the reaction varies depending on the reaction temperature and the type of solvent, a reaction time of 0.1 to 30 hours is usually sufficient.

In this way, a reaction liquid containing a dialkyl dicarbonate to be washed with water can be produced.

The reaction solution obtained is first treated to remove by-product salts. The method of removing the by-product salt is not particularly limited,
Examples thereof include a method by solvent extraction, a method by filtration, a method of desalting with an ion exchange membrane, and a method of washing with water. In the method of washing with water, it may be carried out in combination with the subsequent treatment of adjusting the pH and electric conductivity of the water after washing with water to a specific range. In this case, you may wash continuously with countercurrent distribution.

In the present invention, the pH of water used for washing with water is 4.5 to 7.0, preferably 4.7 to 6.8.
Further, it is necessary to carry out the water washing until the electric conductivity of the water before use for washing with water is up to 200 μS, preferably the electric conductivity of the water before use for washing with water is −180 μS.

As a method for adjusting the pH and the electric conductivity within the specified ranges, a method of repeatedly performing washing with water until the pH and the electric conductivity of the water after washing reach the above specified range, and a method of washing the water after the washing with water If the pH is below 4.5,
Next, after washing with an alkaline aqueous solution, a method of further washing with water to adjust the pH and the electric conductivity within the above-mentioned specific ranges. The method of adjusting the pH and the electric conductivity within a specific range by further washing with water after washing with the above method is preferably adopted.

The alkaline aqueous solution used for adjusting the pH of the above-mentioned water after washing is not particularly limited, but may be sodium hydrogen carbonate, sodium carbonate, sodium hydroxide, potassium hydrogen carbonate, potassium carbonate, potassium hydroxide or the like. An aqueous solution is exemplified. If the concentration is too high, it is not economical, so the pH range of 8 to 12 is preferable. Also, a basic anion exchange resin can be used.

The acidic aqueous solution is not particularly limited,
Examples include aqueous solutions of citric acid, sodium hydrogensulfate, potassium hydrogensulfate, acetic acid, hydrochloric acid, sulfuric acid and the like. If the acid concentration is too high, it is not economical, so a pH range of 2-4 is preferred. Moreover, an acidic cation exchange resin can also be used.

The amounts of water, alkaline aqueous solution and acidic aqueous solution to be used are not particularly limited, but they are usually used in the range of 50 to 2000 mL per 1 mol of the alkyl carbonate alkali metal salt used in the reaction.

The water used in the present invention may be ordinary tap water, and generally has a pH of 5.8 to 8.
6. Water having an electric conductivity of 100 μS or less is used. In this way, washing with water is carried out, pH and electric conductivity are adjusted, and then distillation is carried out.

In the present invention, a known method can be adopted as the method of distillation purification after washing with water without any limitation.
For example, either a batch type distillation method or a continuous distillation method can be used. Usually, after distilling off the solvent, a small amount of low-boiling component is distilled off and further concentrated to distill the main component dialkyl dicarbonate to obtain high-purity dialkyl dicarbonate.

When the distillation temperature is too high, the decomposition amount of dialkyl dicarbonate increases, and when it is too low, a high vacuum is required. Therefore, the distillation temperature is usually 30 to 150 ° C., preferably 30 to 100 ° C. To be done. If the degree of vacuum is too low, the boiling point of the dicarbonic acid dialkyl ester will be high, the amount of decomposition of the dicarbonic acid dialkyl ester will increase, and if it is too high, the decompression device will be too large.
It is carried out in the range of 0.1 to 20 mmHg.

In this way, a high-purity dicarbonic acid dialkyl ester can be produced in good yield.

[0037]

According to the present invention, a high-purity dialkyl dicarbonate can be obtained in a high yield by treating it by a simple method. Therefore, the method of the present invention is industrially very useful.

[0038]

EXAMPLES The present invention will be described below with reference to examples.
The invention is not limited to these examples.

Example 1 2100 g of sodium t-butyl carbonate was dispersed in 6680 mL of toluene in a stainless reactor equipped with a stirrer, a thermometer, and a gas introduction tube to prepare N, N, N ', N'-.
Tetramethylethylenediamine 17.4 g, N, N-dimethylformamide 782.6 g, and p-toluenesulfonyl chloride 1329.8 g were added, and 1 Kg / cm ²
CO ₂ was injected under pressure at G, and the mixture was reacted at a temperature of 40 to 45 ° C. for 8 hours. After the reaction, 6680 ml of water was added to dissolve the precipitated crystals, and the toluene layer and the aqueous layer were separated. For the toluene layer, 2230 mL of water was further used, and washing with water was repeated while measuring pH and electric conductivity. After washing with water three times, the pH of the aqueous layer after use for washing was 5.75, and the electric conductivity was 89 μS (water before using for washing; pH 6.9.
5, 74 μS).

Dicarbonic acid dicarbonate in the toluene layer after washing with water
When t-butyl was quantified, 1400.0 g (yield 85.
5%). The toluene layer was concentrated under reduced pressure to remove toluene, and di-t-butyl dicarbonate was further distilled off for 16 hours under the conditions shown in Table 1 using a simple distillation apparatus. The purity and the distillation yield of the di-t-butyl dicarbonate recovered by distillation were determined, and the di-t-butyl dicarbonate remaining at the bottom of the column was determined.
The decomposition rate of di-t-butyl dicarbonate including -butyl was determined, and the results shown in Table 1 were obtained.

Example 2 After the reaction and the removal of by-product salts were carried out in the same manner as in Example 1,
The toluene layer was washed with 2230 mL of water. The pH of the water layer after use for washing with water is 7.10, the electric conductivity is 488 μS (water before use for washing with water; pH
6.95, 74 μS). Then, after washing with 2230 mL of a 5% citric acid aqueous solution, the toluene layer was further washed with 2230 mL of water while measuring pH and electric conductivity. After being washed twice and then used for washing, the pH of the aqueous layer is 5.25 and the electric conductivity is 95.
It was μS.

Dicarbonic acid di-carbonate in the toluene layer after washing with water
When t-butyl was quantified, 1389.7 g (yield 84.
9%). This toluene layer was concentrated under reduced pressure to remove toluene, and further, using a simple distillation apparatus, Example 1 was used.
The results shown in Table 1 were obtained in the same manner as in.

Example 3 17.85 kg of sodium t-butyl carbonate was dispersed in 128 L of toluene in a glass reactor equipped with a stirrer, a thermometer, and a gas inlet tube, and stirred vigorously at 20 ° C. Meanwhile, N, N-dimethylformamide 12.04k
127.5 triethylbenzylammonium chloride in g
The solution containing g was then added to 34 L of toluene over 1 hour.
P-toluenesulfonyl chloride 9.72 dissolved in
kg of solution was added. After the addition, stirring was continued at the same temperature for 6 hours. After the reaction, 56.8 L of water was added to dissolve the precipitated crystals, and the toluene layer and the water layer were separated. Further, 19.0 L of water was used for the toluene layer, and washing with water was repeated while measuring pH and electric conductivity. The pH of the aqueous layer after being washed twice and then used for washing is 2.30, and the electric conductivity is 3.90 mS (water before being used for washing; pH 6.9.
5, 74 μS).

Next, a 5% aqueous sodium hydrogencarbonate solution 19.
After washing with 0 L, the toluene layer was washed for an additional 19.
Washing was repeated using 0 L of water while measuring pH and electric conductivity. The aqueous layer after being washed twice with water and then used for washing had a pH of 5.50 and an electric conductivity of 105 μS. When the amount of di-t-butyl dicarbonate in the toluene layer after washing with water was quantified, it was 1375 g (yield 9.9%). This toluene layer is concentrated under reduced pressure to remove toluene,
Furthermore, using a simple distillation apparatus, the results shown in Table 1 were obtained in the same manner as in Example 1.

Example 4 The same procedure as in Example 1 was carried out to obtain a toluene layer which had been washed with water. The toluene layer was concentrated under reduced pressure to remove toluene, and di-t-butyl dicarbonate was distilled under the conditions shown in Table 1 using a thin film distillation apparatus. The results are shown in Table 1.

Comparative Example 1 After the reaction and the removal of by-product salts were carried out in the same manner as in Example 2,
The toluene layer was washed with 2230 mL of water. The pH of the aqueous layer after use for washing with water is 7.10, the electric conductivity is 488 μS (water before using for washing with water; pH
6.95, 74 μS). When quantifying di-t-butyl dicarbonate in the toluene layer in this state, it was 1400.0
It was g (yield 85.5%). This toluene layer was concentrated under reduced pressure to remove toluene, and the results shown in Table 1 were obtained in the same manner as in Example 1 using a simple distillation apparatus.

Comparative Example 2 After the reaction was carried out in the same manner as in Example 3, the reaction was carried out with 42.5 L of water.
The aqueous layer after being washed twice, washed three times with water and then used for washing had a pH of 2.32 and an electric conductivity of 3950 μS (water before being used for washing; pH 6.95, 74 μS). When quantifying di-t-butyl dicarbonate in the toluene layer in this state, 1
It was 377 g (yield 9.9%). The toluene layer was concentrated under reduced pressure to remove toluene, and the results shown in Table 1 were obtained in the same manner as in Example 1 using a simple distillation apparatus.

[0048]

[Table 1]

Claims (1)

[Claims] 1. The pH of water after use of a dicarbonic acid dialkyl ester obtained by reacting an alkali metal carbonate of carbonic acid with an acid halide for washing with water is 4.5 to 7.0.
And a method for producing a dialkyl dicarbonate ester, which comprises distilling after washing with water until the electrical conductivity of the water before being used for washing with water is up to 200 μS.