JP2892866B2 - Preparation of α, β-epoxycarboxylic acid derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing an α, β-epoxycarboxylic acid derivative. More specifically, for example, α, β-epoxycarboxylic acid derivatives which can be suitably used as intermediates such as pharmaceuticals, agricultural chemicals, and liquid developers for electrostatography can be produced inexpensively, safely and with high yield under mild conditions. A process that can be manufactured.

[0002]

2. Description of the Related Art In recent years, α, β-epoxycarboxylic acid derivatives have been widely used as intermediates for pharmaceuticals, agricultural chemicals and the like.

As a general method for producing an α, β-epoxycarboxylic acid derivative, for example, (a) (meth) acrylic acid ester is used as an oxidizing agent,
-Oxidation using chloroperbenzoic acid (mCPBA) (Journal of Polymer Science (J. Polym. Sci.) 22, 2501, 1984; Journal
Of Medicinal Chemistry (J.Med.Chem.) 29
Volume, 2184, 1986; Tetrahedron Letters (Tetr
ahedron Lett.) 21, p. 1833, 1979), (b) (meth) acrylic acid ester as an oxidizing agent,
Oxidation using F ₃ CO ₃ H (Synthetic
Communications (Synth. Commun.) Volume 4, Issue 5, 25
5 pages, 1975; Journal of the Chemical Society, Perkin Transactions I (J. Chem.
Soc., Perkin Trans. I) No. 23, p. 2517, 1975), (c) A method of oxidizing (meth) acrylic acid ester with hydrogen peroxide (Journal of the Institution of the Chemist (J. Inst. Chem.) 55 volumes,
159, 1983; Journal of Indian Chemical Society (J. Indian Chem. Soc.) 974,
1986).

[0004] However, the method (a) using mCPBA as an oxidizing agent is disadvantageous in that the mCPBA is expensive and is not economical, and that the yield of the obtained epoxycarboxylic acid derivative is low. CF ₃ CO
_In the method (b) using ₃ H as an oxidizing agent, the CF ₃
CO ₃ H is expensive and has the drawback that it is not economical because it requires an equivalent amount or more, and the method (c) using hydrogen peroxide as the oxidizing agent gives the epoxycarboxylic acid derivative obtained. Has a drawback that it is not suitable as a method for industrial production because of low yield.

[0005]

Therefore, in view of the above-mentioned prior art, the present inventors have economically produced α, β-epoxycarboxylic acid derivatives from starting materials under mild conditions in a short time and with high yield. As a result of intensive studies for the purpose of developing a process which can be produced, the α, β-unsaturated carboxylic acid derivative was prepared in the presence of a quaternary onium salt in an organic / aqueous two-phase medium. The inventors have found that the above object can be achieved when oxidized by halogenous acid ions, and have completed the present invention.

[0006]

That is, the present invention relates to α,
α, β-epoxycarboxylic acid derivatives, characterized in that the β-unsaturated carboxylic acid derivative is oxidized by hypohalous acid ions in a two-phase organic / aqueous medium in the presence of a quaternary onium salt. Regarding the manufacturing method.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The method for producing the α, β-epoxycarboxylic acid derivative of the present invention comprises, as described above, a method of preparing an α, β-unsaturated carboxylic acid derivative from an organic layer in the presence of a quaternary onium salt.
It is characterized in that it is oxidized by hypohalite ions in a two-phase medium in an aqueous layer.

A typical example of the α, β-unsaturated carboxylic acid derivative used in the present invention is, for example, a compound represented by the following general formula (I):

[0009]

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Wherein R ¹ is a hydrogen atom, —COOR
⁴ (R ⁴ represents an alkyl group having 1 to ⁴ carbon atoms) or

[0011]

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(Wherein, R ⁵ represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an oxyalkyl group having 1 to 4 carbon atoms), R ² represents a hydrogen atom or an alkyl group having 1 to 2 carbon atoms,

[0013]

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R ³ is an alkyl group having 1 to 20 carbon atoms or

[0015]

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(M represents an integer of 0 to 4 and n represents an integer of 0 to 20).

Specific examples of the α, β-unsaturated carboxylic acid derivative include, for example, methyl acrylate, ethyl acrylate, propyl acrylate, n-butyl acrylate,
Methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, n- crotonate
Perfluoro acrylates such as butyl, dimethyl fumarate, diethyl fumarate, dipropyl fumarate, dimethyl maleate, diethyl maleate, dipropyl maleate, methyl cinnamate, n-butyl cinnamate, perfluorooctylethyl acrylate Alkyl, perfluoroalkyl methacrylate such as perfluorooctylethyl methacrylate, t-butyl acrylate, t-butyl methacrylate, methyl crotonate, ethyl crotonate, propyl crotonate, t-butyl crotonate, p-methoxysilicate Examples thereof include methyl cinnamate, dimethyl itaconate, and n-butyl α-hydroxymethyl acrylate.

The α, β-unsaturated carboxylic acid derivative is
The α, β-unsaturated carboxylic acid derivative and the resulting α, β
The β-epoxycarboxylic acid derivative is dissolved in the organic layer so as not to be contained in the aqueous layer. The organic solvent used for the organic layer is not particularly limited as long as it does not mix with water, does not react with itself, and dissolves the α, β-unsaturated carboxylic acid derivative and the generated unsaturated epoxycarboxylic acid derivative. There is no limitation. Specific examples of such organic solvents include, for example, ethyl acetate, benzene, toluene,
Examples include xylene, chlorobenzene, pentane, hexane, cyclohexane, methylene chloride, chloroform, dichloroethane, and the like, but the present invention is not limited to such examples. The concentration of the α, β-unsaturated carboxylic acid derivative in the organic layer is 5 to 60% by weight, especially
It is preferably 15 to 25% by weight. If the concentration of the α, β-unsaturated carboxylic acid derivative is smaller than the above range, a large amount of the organic phase must be handled, which requires a long time for the recovery step and is economically disadvantageous. If it is larger than the above range, the loss to the aqueous phase increases,
Since a recovery operation from the aqueous phase such as extraction is required, the number of steps is increased, which is economically disadvantageous.

The quaternary onium salt used in the present invention is a phase transfer catalyst having a catalytic effect of solubilizing an anionic nucleophilic species insoluble in an organic solvent. Specific examples of the quaternary onium salt include, for example, trioctylmethylammonium chloride, tri-n-butylbenzylammonium chloride, tetra-n-butylammonium iodide, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n -Butylphosphonium bromide, tetra-n-butylammonium hydrogen sulfate, cetyltrimethylammonium bromide, tetramethylammonium chloride, triethylbenzylammonium chloride, N-cetylpyridinium chloride, N-laurylpyridinium chloride, tetraphenylphosphonium bromide and the like. However, among these, trioctylmethylammonium chloride and tri-n-butylbenzylammonium chloride , Tetra-n- butylammonium chloride, tetra-n- butylammonium hydrogen sulfate are those which can be used particularly suitably in the present invention. The amount of the quaternary onium salt is 1 to 10 mol, preferably 1 to 5 mol, per 100 mol of the α, β-unsaturated carboxylic acid derivative.
Preferably it is molar. If the amount of the quaternary onium salt is less than the above range, the α, β-unsaturated carboxylic acid derivative will be decomposed by hypohalite ions, and if it is more than the above range, Is
The effect is hardly improved by adding more than that, which is rather disadvantageous economically. The quaternary onium salt is added to the α, β before contacting the hypohalite ion.
-Incorporated in the organic layer together with the unsaturated carboxylic acid derivative.

The hypohalous acid ion used in the present invention is
Obtained by dissolving hypohalite in water.
The hypohalite is excellent in safety, such as being inexpensive, less toxic, and less adversely affecting the environment. Specific examples of such hypohalites include, for example, sodium hypochlorite, alkali metal hypochlorite such as potassium hypochlorite, calcium hypochlorite, and hypochlorite such as barium hypochlorite. Alkaline earth metal salts, such as sodium hypobromite and potassium hypobromite, alkaline earth metal hypobromite salts such as calcium hypobromite and barium hypobromite Among these, sodium hypochlorite, calcium hypochlorite, etc. are industrially mass-produced for uses such as bleaching agents, disinfectants, etc., and are available at low cost. Therefore, it can be suitably used.

The hypohalite is added to the aqueous layer to generate hypohalite ions, and the concentration of the hypohalite ion depends on the concentration of the hypohalite added to the aqueous layer. It can be specified in quantity. If the concentration of hypohalite is too high, the hypohalite becomes unstable and handling becomes difficult, and if it is too low, a large amount of aqueous layer is formed. Is required, which causes a delay in the reaction time and a decrease in the yield. Therefore, the amount is usually preferably 1 to 20% by weight, more preferably 10 to 13% by weight.

The ratio between the α, β-unsaturated carboxylic acid derivative and the hypohalite ion is usually a stoichiometric amount, but improves the reaction yield of the α, β-unsaturated carboxylic acid derivative. For this purpose, it is preferable to adjust the amount of hypohalous acid ion (hypohalite) to 1.5 to 3.5 mol per mol of the α, β-unsaturated carboxylic acid derivative.

Oxidation of the α, β-unsaturated carboxylic acid derivative with hypohalite ion is carried out by combining an organic layer containing the α, β-unsaturated carboxylic acid derivative and a quaternary onium salt with a hypohalite ion. It can be carried out by bringing the aqueous layer into contact with the water. In the reaction, the organic layer and the aqueous layer may be charged at once, or the aqueous layer may be dropped on the organic layer, but the latter is preferred because the reaction proceeds uniformly. The reaction temperature is not particularly limited,
If the temperature is lower than 0 ° C., the reaction rate becomes slow and industrially uneconomical. If the temperature exceeds 100 ° C., the decomposition of the hypohalite used becomes severe, and the conversion is significantly reduced.
The temperature is preferably from 100 ° C., especially from room temperature to reflux temperature. In the present invention, a lower reaction temperature is more preferable because the yield can be easily improved. The atmosphere during the reaction is not particularly limited, and may be ordinary air or an inert gas such as nitrogen gas or argon gas.

The time required for the reaction varies depending on the kind of the α, β-unsaturated carboxylic acid derivative, its compounding amount, the reaction temperature and the like, and cannot be unconditionally determined.
Usually, the reaction is completed in a relatively short time of 4 to 8 hours.

The end point of the reaction can be confirmed, for example, by examining the change between the raw material and the product by gas chromatography or the like.

After completion of the reaction, the organic layer and the aqueous layer are separated, and the organic layer is taken out. Since the organic layer contains hypohalous acid ions, it is preferable to wash the organic layer with an aqueous solution of a reducing agent such as an aqueous solution of sodium thiosulfate.

Next, the organic layer is concentrated, and an α, β-epoxycarboxylic acid derivative produced by an operation such as distillation can be isolated.

The structure of the resulting α, β-epoxycarboxylic acid derivative can be easily confirmed by ¹ H-NMR, IR and the like.

Next, the method for producing the α, β-epoxycarboxylic acid derivative of the present invention will be described in detail with reference to Examples.
The present invention is not limited to only such embodiments.

Example 1 A 30 ml glass reaction vessel was charged with n-butyl acrylate.
50 g (18.9 mmol), 0.96 g (1.9 mmol) of 80% trioctylmethylammonium chloride and 12.5 g of ethyl acetate were weighed, and 17.6 g of a 12% aqueous sodium hypochlorite solution was added to this mixed solution while stirring at room temperature. The reaction was continued by further stirring for 3 hours after the completion of the dropwise addition, and the disappearance of n-butyl acrylate was confirmed by gas chromatography. The reaction yield was 96% (2.62 g).

Next, the organic layer and the aqueous layer of the reaction solution were separated, and the organic layer was separated into 2 g of a 1% aqueous solution of sodium thiosulfate and 10 g of an aqueous solution.
2% aqueous solution of sodium sulfate, concentrated, and the residue was distilled. The residue was n-butyl glycidate (boiling point 62-65 ° C / 4 mm
Hg) 2.51 g (92% isolated yield).

The identification of the n-butyl glycidate obtained was ¹
H-NMR was used. The results are shown below.

¹ H-NMR (solvent: CDCl ₃ , internal standard: TMS) 270 MHz δ = 1.0 ppm (3H, d, J = 6 Hz) CH ₃ δ = 1.2 to 1.8 ppm (4H, m) CH ₂ CH ₂

[0034]

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[0035]

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Δ = 4.21 ppm (2H, t, J = 6 Hz) O = COCH ₂ Example 2 In Example 1, the amount of the 12% sodium hypochlorite aqueous solution was changed to 14.1 g and it took 2 hours. The reaction was carried out in the same manner as in Example 1 except that the mixture was added dropwise and the mixture was further stirred for 6 hours after completion of the addition, and the disappearance of n-butyl acrylate was confirmed by gas chromatography. Reaction yield 82% (yield
2.23 g).

Next, after isolation in the same manner as in Example 1, identification was carried out to obtain 20.4 g of n-butyl glycidate (isolation yield: 75%).

Example 3 In Example 1, the blending amount of 80% trioctylmethylammonium chloride was changed to 0.48 g (0.95 mmol), and the dripping time of 17.6 g of 12% aqueous sodium hypochlorite solution was changed to 4 hours. The reaction was carried out in the same manner as in Example 1 except that the reaction was changed and stirring was continued for 4 hours after the completion of the dropwise addition, and the disappearance of n-butyl acrylate was confirmed by gas chromatography. The reaction yield was 94% (yield 2.56 g).

Next, after isolation in the same manner as in Example 1, identification was performed to obtain 2.40 g of n-butyl glycidate (isolation yield: 88%).

Example 4 A reaction was carried out in the same manner as in Example 3 except that the blending amount of 80% trioctylmethylammonium chloride was changed to 96 mg (0.19 mmol) to eliminate n-butyl acrylate. Was confirmed by gas chromatography. The reaction yield was 81% (2.21 g).

Then, after isolation in the same manner as in Example 3, identification was carried out to obtain 1.99 g of n-butyl glycidate (isolation yield: 73%).

Example 5 n-Butyl acrylate 2. was placed in a 30 ml glass reaction vessel.
50 g (18.9 mmol), benzyltri-
0.59 g (1.9 mmol) of n-butylammonium chloride and 12.5 g of ethyl acetate were weighed, and 17.6 g of a 12% aqueous sodium hypochlorite solution was added to this mixed solution at room temperature with stirring, followed by stirring for 9 hours. After the reaction, disappearance of n-butyl acrylate was confirmed by gas chromatography.
The reaction yield was 85% (2.32 g).

Next, the organic layer and the aqueous layer of the reaction solution were separated, and the organic layer was separated into 2 g of a 1% aqueous solution of sodium thiosulfate and
The mixture was washed successively with 2 g of a 10% aqueous sodium sulfate solution, concentrated, and the remaining liquid was distilled to obtain 2.18 g of n-butyl glycidate (isolation yield)
80%).

When the obtained n-butyl glycidate was identified by ¹ H-NMR in the same manner as in Example 1, similar measurement results were obtained.

Example 6 A reaction was carried out in the same manner as in Example 5 except that 0.53 g (1.9 mmol) of tetra-n-butylammonium chloride was used as a phase transfer catalyst. Disappearance was confirmed by gas chromatography.
The reaction yield was 85% (2.32 g).

Next, after isolation in the same manner as in Example 1, identification was carried out to obtain 2.10 g of n-butyl glycidate (isolation yield: 77%).

Example 7 In Example 5, 0.64 g of tetra-n-butylammonium hydrogen sulfate (1.
The reaction was carried out in the same manner as in Example 5 except that 9 mmol) was used, and disappearance of n-butyl acrylate was confirmed by gas chromatography. The reaction yield was 76% (yield 2.07 g).

Next, after isolation in the same manner as in Example 1, identification was carried out to obtain 1.77 g of n-butyl glycidate (isolation yield: 65%).

Examples 8 to 14 In Example 3, instead of n-butyl acrylate,
The reaction was carried out in the same manner as in Example 3 except that the α, β-unsaturated carboxylic acid derivative shown in Table 1 was used, and disappearance of the α, β-unsaturated carboxylic acid derivative was confirmed by gas chromatography. The reaction yield and yield are shown in Table 1.

Next, after isolation in the same manner as in Example 1, identification was carried out to obtain α, β-epoxycarboxylic acid derivatives shown in Table 1. Table 1 shows the isolation yield and yield.

[0051]

[Table 1]

As is clear from the above results, according to the production method of the present invention, a reaction operation such as heating and cooling is not required, and α α can be obtained in a high yield only by conducting the reaction in the air at room temperature. , Β-epoxycarboxylic acid derivative can be obtained.

[0053]

According to the production method of the present invention, inexpensive hypohalous acid ions are used in the reaction, so that the process is excellent in economical efficiency and can be carried out from the α, β-unsaturated carboxylic acid derivative as a starting material. The α, β-epoxycarboxylic acid derivative can be easily produced in a short time and in a high yield under mild conditions.

Accordingly, the production method of the present invention is capable of producing an α, β-epoxycarboxylic acid derivative industrially, stably and efficiently, and thus makes a great advance in this technical field.

Continuation of front page (58) Field surveyed (Int.Cl. ⁶ , DB name) C07D 301/03 C07D 303/00-303/38

Claims (1)

(57) [Claims] 1. An α, β-unsaturated carboxylic acid derivative is oxidized by hypohalite ion in a biphasic medium of an organic layer / aqueous layer in the presence of a quaternary onium salt. Production method of β-epoxycarboxylic acid derivative.