JP3061315B2 - Method for producing dialkyl dicarbonate - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a dialkyl dicarbonate by reacting an alkali metal alkoxide with carbon dioxide and then reacting the obtained alkyl carbonate alkali metal salt with an aromatic sulfonyl halide. Related to the method of manufacturing at a rate.

[0002]

2. Description of the Related Art Dialkyl dicarbonate is a compound which has long been known as a food preservative.
It is increasingly important as a protective agent for amino acids in peptide chemistry.

Heretofore, as a method for synthesizing a dialkyl dicarbonate, a method of reacting an alkali metal salt of an alkyl carbonate with an aromatic sulfonyl chloride in the presence of N, N-dimethylformamide and a quaternary ammonium salt (Czechoslovak Patent No. 25,157) and a method of reacting pyridine with a quaternary ammonium salt (Czechoslovak Patent No. 260,076).

It is also known to react monosodium carbonate with an aromatic sulfonyl chloride having hydrogen or halogen at the para-substituent in acetone to obtain a dialkyl dicarbonate (Japanese Patent Publication No. Sho 42-42). 1
No. 9818).

[0005]

When the former two methods are used, the yields based on aromatic sulfonyl chloride are 66% and 84.9%, respectively. However, although the aromatic sulfonyl chloride requires 1/2 mole amount of the alkali metal salt of the alkyl carbonate, only 80% of the required amount is actually used.
For this reason, the yield is higher than the yield based on the alkali metal carbonate of the alkyl carbonate.

Therefore, when the above yield is converted into a yield based on an alkali metal salt of an alkyl carbonate, they are 52.8% and 67.9%, respectively, which are not sufficiently high.

In the latter, an acetone solvent is used to dissolve the starting material alkali metal alkyl carbonate, but acetone reacts with the alkali metal alkoxide. It must be manufactured and used once recovered and purified, which is inconvenient in that it is not possible to consistently manufacture from an alkali metal alkoxide to a dialkyl dicarbonate.

[0008]

Means for Solving the Problems The present inventors diligently seek a method for synthesizing a target compound in a better yield by an integrated production from the reaction of an alkali metal alkoxide with carbon dioxide to the production of a dialkyl dicarbonate. As a result of the examination, the content of the alkali metal hydroxide contained as an impurity in the alkali metal alkoxide as the raw material affects the reaction between the alkali metal salt of the alkyl carbonate carbonate and the aromatic sulfonyl halide in the next step, and The present inventors have found that a dialkyl dicarbonate can be produced in a high yield by suppressing the content of an alkali metal hydroxide in an alkali metal alkoxide to a low level, thereby completing the present invention.

That is, according to the present invention, the reaction is carried out by introducing carbon dioxide into an organic solvent containing 2 to 40% by weight of an alkali metal alkoxide to form an alkali metal salt of an alkyl carbonate, and then the reaction mixture is added to the reaction mixture. A step of adding and reacting an aromatic sulfonyl halide and a tertiary amine represented by the following formula (I) to obtain a dialkyl dicarbonate, and first using the amount of alkali hydroxide present in the system. A method for producing a dialkyl dicarbonate, which is maintained at 10 mol% or less based on the alkali metal alkoxide.

[0010]

Embedded image [However, R ⁴ and R ⁵ are the same or different alkyl groups, R ⁶ is an alkylene group, and Y is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group or

[0011]

Embedded image Wherein R ⁷ and R ⁸ are a hydrogen atom or an alkyl group, at least one of which is an alkyl group, Z is O, S or> NR ⁹ (where R ⁹ is a hydrogen atom or an alkyl group), and n is 1 And m is 0 or 1]. In the present invention, the alkali metal alkoxide as a raw material is represented by the following general formula.

R-OM (where R is an alkyl group and M is an alkali metal) Specific examples of the alkali metal alkoxide include, for example, sodium methoxide, sodium ethoxide, and sodium isopropoxide. , Sodium isobutoxide, sodium-t-butoxide, sodium
Examples thereof include t-amyloxide, potassium isopropoxide, potassium-t-butoxide, and potassium-t-amyloxide.

These alkali metal alkoxides are obtained by dispersing a corresponding alcohol in a solvent and reacting with an alkali metal, and may be used by isolation by a known method, or may be used as it is in some cases. In general, water is contained in alcohol, and in the production process of the alkali metal alkoxide, the water reacts with the alkali metal to generate an alkali metal hydroxide, which is mixed as an impurity in the alkali metal alkoxide. Will be. Further, the generated alkali metal alkoxide itself is decomposed by moisture absorption to generate an alkali metal hydroxide.

Therefore, in the present invention, the alkali metal alkoxide to be used must be sufficiently controlled and used before purification.

That is, in the present invention, in order to obtain a dialkyl dicarbonate in a high yield, the content of the alkali metal hydroxide contained in the raw material alkali metal alkoxide is adjusted to 100 moles of the alkali metal alkoxide. It is essential that the content be 10 mol or less. Further, the content of the alkali metal hydroxide is preferably low, and is preferably 7 mol or less, more preferably 5 mol or less, per 100 mol of the alkali metal alkoxide. By doing so, the action of the tertiary amine as a catalyst can be improved in the subsequent step of forming a dialkyl dicarbonate, which is the next reaction step, and a dialkyl dicarbonate can be obtained in a high yield.

Specific examples of the alkali metal hydroxide in the present invention include sodium hydroxide and potassium hydroxide.

The method for analyzing the alkali metal hydroxide in the alkali metal alkoxide is not particularly limited.
It can be performed by combining gas chromatography and the method of JIS K-1200.

The reaction between the alkali metal alkoxide having a low content of the alkali metal hydroxide and carbon dioxide is carried out to obtain an alkyl carbonate alkali metal salt. The reaction between the alkali metal alkoxide and carbon dioxide can be usually performed by introducing carbon dioxide into an organic solvent containing the alkali metal alkoxide.

The carbon dioxide in the above reaction is not particularly limited, and either gas or solid can be used.

In the present reaction, the viscosity of the reaction solution increases as the production of the alkyl carbonate alkali metal salt proceeds, so that the concentration of the alkali metal alkoxide is 2 to 40.
It is desirable to dilute with a solvent so that the weight% may be obtained. The solvent used is not particularly limited, and aromatic hydrocarbons such as benzene, toluene and xylene; ether compounds such as 1,4-dioxane and tetrahydrofuran; acetonitrile, N, N-dimethylformamide, N-methylpyrrolidone and the like are used. Is done. Further, an alcohol corresponding to an alkali metal alkoxide as a raw material can also be used. In addition, these organic solvents may be used alone or as a mixture of two or more kinds.

The reaction temperature in the present reaction is not particularly limited, but is preferably 100 ° C. or lower in order to prevent the decomposition of the formed alkyl carbonate carbonate alkali metal salt.

The reaction can be carried out at normal pressure, increased pressure or reduced pressure. The time required for the reaction varies depending on the alkali metal alkoxide used, the reaction temperature and the type of the solvent. 30 hours is enough.

Thus, an alkali metal carbonate of an alkyl carbonate can be obtained. The alkali metal carbonate alkyl carbonate is represented by the following general formula.

[0024]

Embedded image (However, R ¹ is an alkyl group and M is an alkali metal.) Specific examples of the above-mentioned alkali metal alkyl carbonate carbonate include, for example, sodium methyl carbonate, sodium ethyl carbonate, sodium isopropyl carbonate, and sodium carbonate. Isobutyl, sodium t-butyl carbonate,
Examples thereof include sodium t-amyl carbonate, potassium methyl carbonate, potassium ethyl carbonate, potassium isopropyl carbonate, potassium isobutyl carbonate, potassium t-butyl carbonate, and potassium t-amyl carbonate.

Next, the reaction of the alkali metal alkyl carbonate with the aromatic sulfonyl halide is carried out. In this reaction, as the alkali metal salt of the alkyl carbonate carbonate, the reaction mixture is used as it is after the reaction between the alkali metal alkoxide and carbon dioxide.

As the aromatic sulfonyl halide to be reacted with the above-mentioned alkali metal salt of the alkyl carbonate, any known compound having a halogeno sulfone group bonded to an aromatic ring can be used without any limitation. In the present invention, the following formula

[0027]

Embedded image (However, R ² and R ³ are a hydrogen atom, a halogen atom, and an alkyl group, and X is a halogen atom.).

Specific examples of the aromatic sulfonyl halide which can be suitably 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 aromatic sulfonyl halide based on the alkali metal salt of the alkyl carbonate is usually one molecule of the alkali metal salt of the alkyl ester because one molecule of the dialkyl dicarbonate is formed from two molecules of the alkali metal salt of the alkyl carbonate. 0.3-0.
It is selected in a range of 5 mol.

In the above reaction, a catalyst is used to make the reaction proceed. As the catalyst, an aliphatic tertiary amine or an aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an alkylene group are suitably used because the target compound is obtained in high yield. In particular, in the present invention, the following formula (I)

[0031]

Embedded image [However, R ⁴ and R ⁵ are the same or different alkyl groups, R ⁶ is an alkylene group, and Y is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group, or

[0032]

Embedded image [However, R ⁷ and R ⁸ are a hydrogen atom or an alkyl group, at least one of them is an alkyl group, and Z is O, S or> NR ⁹ (provided that R ⁹ is a hydrogen atom or an alkyl group). And n is an integer of 1 or more, and m is 0 or 1]. ] Can be employed.

Specific examples of the aliphatic tertiary amine which can be suitably used in the present invention or an aromatic tertiary amine 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) ethylethyl sulfide, bis-
[2- (N, N-dimethylamino) ethyl] methylamine and the like can be mentioned.

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

[0035]

Embedded image (However, when R ⁷ and R ⁸ are a hydrogen atom or an alkyl group, at least one of which is an alkyl group), the yield of the target compound is particularly high, so that
It is suitably used in the present invention.

The amount of the above-mentioned aliphatic tertiary amine or aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom through an alkylene group is not particularly limited, but a sufficient reaction rate is required. In order to obtain it, the content is preferably in the range of 0.01 to 20 mol%, more preferably 0.05 to 10 mol%, based on the alkali metal salt of the alkyl carbonate.

In the present reaction, the concentration of the alkali metal alkyl carbonate is 3 to 3 to improve the dispersibility of the reaction solution.
It is desirable to dilute with a solvent so as to be 60% by weight. For this purpose, a solvent can be added. The solvent is not particularly limited, and aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as 1,4-dioxane and tetrahydrofuran; acetonitrile, methylpyrrolidone, N, N-dimethylformamide and the like are used. Further, an alcohol corresponding to the alkyl group in the alkali metal salt of the alkyl carbonate can also be used. These organic solvents may be used alone,
Use of a mixed solvent of two or more types does not interfere at all.

The reaction temperature in this reaction is not particularly limited. However, if the temperature is too low, the reaction rate is reduced, and if the temperature is too high, the raw material and the target compound are decomposed. C. is preferably carried out at a temperature.

The reaction can be carried out at normal pressure, increased pressure or reduced pressure. The time required for the reaction varies depending on the reaction temperature and the type of solvent, but a reaction of 0.1 to 30 hours is usually sufficient. It is.

Thus, the following equation

[0041]

Embedded image (Wherein R ¹⁰ and R ¹¹ are the same or different alkyl groups).

[0042]

According to the present invention, dialkyl dicarbonate can be obtained under mild conditions with a yield of 80% or more based on the alkali metal carbonate alkoxide.

[0043]

Hereinafter, the present invention will be described with reference to examples.
The present invention is not limited to these embodiments.

Example 1 In a glass autoclave equipped with a stirrer, a thermometer, a cooler and a gas inlet tube, 47.7 g of sodium t-butoxide containing 0.0105 mol of sodium hydroxide (58.
1% by weight, 0.288 mol) was dispersed in 200 ml of toluene, and carbon dioxide was sequentially injected under pressure to ² kg / cm ² ,
The reaction vessel was cooled with water and reacted for 4 hours. afterwards,
0.335 g of N, N, N ', N'-tetramethylethylenediamine, 15.2 N, N-dimethylformamide
2 g, p-toluenesulfonyl chloride 24.73 g
And pressurize CO ₂ at 1 kg / cm ² ,
At a temperature of 8 hours. After the reaction, 120 ml of water was added to dissolve the precipitated crystals, the toluene layer and the aqueous layer were separated, and di-t-butyl dicarbonate in the toluene layer was quantified to give 26.87 g (yield). 85.5%).

Examples 2 to 7 Dialkyl dicarbonates were synthesized in the same manner as in Example 1 using alkali metal alkoxides containing alkali metal hydroxides shown in Table 1. The results are shown in Table 1.

Comparative Examples 1 to 3 Dialkyl dicarbonates were synthesized in the same manner as in Example 1 using alkali metal alkoxides containing alkali metal hydroxides shown in Table 1. The results are shown in Table 1.

[0047]

[Table 1] Examples 8 to 13 Di-t-butyl dicarbonate was synthesized in the same manner as in Example 1 using the catalysts shown in Table 2 instead of N, N, N ', N'-tetramethylethylenediamine. The results are shown in Table 2.

[0048]

[Table 2] Example 14 The same operation as in Example 1 was performed using 22.92 g of benzenesulfonyl chloride instead of p-toluenesulfonyl chloride, to obtain 26.62 g of di-t-butyl dicarbonate (84.7 yield). %).

──────────────────────────────────────────────────続 き Continuation of the front page (56) References Japanese Patent Publication No. 42-19818 (JP, B1) "Chemical Experimental Methods" (1970-7-10) Tokyo Chemical Dojin, p. 214. Chemical Abstracts, 109 (1988) Chemical Abstracts, 109 (1988), 8419. (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 69/96 C07C 68/04 C07C 68/06 BEILSTEIN (STN) CAPLUS (STN) ) REGISTRY (STN) WPIDS (STN)

Claims (1)

(57) [Claims] (1) introducing carbon dioxide into an organic solvent containing 2 to 40% by weight of an alkali metal alkoxide,
Reacting to form an alkali metal salt of an alkyl carbonate, then adding an aromatic sulfonyl halide and a tertiary amine represented by the following formula (I) to the reaction mixture, and reacting to obtain a dialkyl dicarbonate. A process for producing a dialkyl dicarbonate, wherein the amount of alkali hydroxide present in the system is maintained at 10 mol% or less based on the alkali metal alkoxide used initially. Embedded image Wherein R ⁴ and R ⁵ are the same or different alkyl groups, R ⁶ is an alkylene group, and Y is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group or Wherein R ⁷ and R ⁸ are a hydrogen atom or an alkyl group, at least one of which is an alkyl group, Z is O, S or> NR ⁹ (where R ⁹ is a hydrogen atom or an alkyl group), and n is 1 And m is 0 or 1]. ]