JPH0717578B2 - Method for producing dihalogenopropionate - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel method for producing a dihalogenopropionic acid ester with high selectivity and high yield.

[Problems to be Solved by Prior Art and Invention]

Dihalogenopropionic acid ester is a useful compound which can be widely used as an intermediate in agriculture and medicine.

As a conventional method for producing a dihalogenopropionic acid ester, acrylic acid methyl ester is chlorinated or brominated in a methanol solvent to give 2,3-dichloropropionic acid methyl ester or 2,3-dibromopropionic acid methyl ester. get method [journal of the American Chemical Seo Saia Tay (J.Am.Chem.Soc.) 62, 3495 ( 194
0)] or 3-substituted-acrylic acid or a derivative thereof is halogenated using a phosphoric acid-hydrogen salt catalyst of an alkali metal or an alkaline earth metal to obtain 3-substituted-dihalogenopropionic acid or a derivative thereof (special feature Kaisho 56-87531
No.) and the like are known.

However, in the former method, the yield is as low as 85 to 88%, and in the latter method, 3-substituted-trihalogenoacrylic acid or its derivative which is more halogenated than the target compound or 3-
Substituted-tetrahalogen acrylic acid or its derivative is 10
%, And the yield was about 80-90%, and there was room for improvement in selectivity.

[Means for solving problems]

The present inventors have studied an industrial method for producing a dihalogenopropionic ester by reacting an acrylic ester with a halogen to produce a high yield and high selectivity.
As a result, when a reaction is carried out in a liquid phase with a tertiary amine or a tertiary phosphine interposed, a dihalogenopropionic acid ester can be produced with high yield and with little by-products, and with high selectivity. The present invention has been completed and the present invention has been completed.

That is, the present invention relates to the general formula (1) (However, R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and R ₄ represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted An unsubstituted phenyl group) and a halogen are reacted with a halogen in the liquid phase in the presence of a tertiary amine or a tertiary phosphine. (However, R ₁ , R ₂ and R ₃ are a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and R ₄ is a substituted or unsubstituted alkyl group, a substituted or unsubstituted A substituted phenyl group is shown, and X is a halogen atom.) Is a method for producing a dihalogenopropionic acid ester.

One of the raw materials used in the present invention is represented by the general formula (1) (However, R ₁ , R ₂ , R ₃ and R ₄ have the same meaning as described above.). In the general formula (1), the alkyl group represented by R ₁ , R ₂ , R ₃ and R ₄ is not particularly limited in the number of carbon atoms, and a linear or branched saturated group is used. Generally, an alkyl group having 1 to 6 carbon atoms is preferable because of easy availability of raw materials. Generally, specific examples of the most preferably used alkyl group are methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, iso-butyl group, t-butyl group, n- Examples thereof include pentyl group and n-hexyl group. Further, in the general formula, R ₁ and R ₂
Examples of the halogen atom represented by R ₃ include fluorine, chlorine, bromine or iodine. Further, the substituent of the substituted alkyl group is not particularly limited, and a substituent inert to the reaction system can be used without any limitation. Specific examples of the substituent which can be particularly preferably used include a halogen atom; a methoxy group, an ethoxy group, an n-propoxy group, an iso-propoxy group, and n.
An alkoxy group such as a butoxy group; an alkylthio group such as a methylthio group, an ethylthio group, an n-propylthio group, and an n-butylthio group; a phenyl group; a phenoxy group.
The substituent of the substituted phenyl group is not particularly limited, and a substituent inert in the reaction system can be used without any limitation.
As the substituent which can be particularly preferably used, a halogen atom; an alkyl group such as a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, an iso-butyl group and a t-butyl group; a chloro group Examples thereof include halogenoalkyl groups such as methyl group, difluoromethyl group, trifluoromethyl group, trichloromethyl group, trifluoroethyl group and pentafluoroethyl group; and phenyl group.

More specifically, acrylic acid esters that can be particularly preferably used in the present invention are exemplified by acrylic acid methyl ester, acrylic acid t-butyl ester, acrylic acid phenyl ester, 3-methylacrylic acid ethyl ester, and 3,3-dimethylacrylic acid. Acid ethyl ester, 3-ethylacrylic acid, 3-phenylacrylic acid phenyl ester, 3-phenyl-3-
Methylacrylic acid ethyl ester, 2-chloroacrylic acid methyl ester, 3-phenyl-2-fluoroacrylic acid methyl ester, 2-methylacrylic acid methyl ester, 2
-Iso-propylacrylic acid, 3-trichloromethyl-2
-T-butylacrylic acid butyl ester, 3-n-hexyl-2-iodoacrylic acid propyl ester, 3-penta-2-ethylthiomethylacrylic acid iso-propyl ester, 3,3-dimethyl-2-bromoacrylic acid t-Butyl ester, 3,3-dichloroacrylic acid methyl ester, 3-
Chloro-2-methoxymethylacrylic acid n-hexyl ester, 3-n-propoxymethyl-2-methylacrylic acid phenyl ester, 3-phenoxy-2-methylthiomethylacrylic acid methyl ester, 3-methyl-2-p- Chlorophenyl acrylic acid methyl ester, 3-p-methylphenyl acrylic acid methyl ester, 3- (op-dichlorophenyl) -2-jodomethyl acrylic acid methyl ester, 3,3-dimethyl-2-pt- Butylphenyl acrylic acid ethyl ester, 3-bromomethyl-2-iso-
Propoxymethylacrylic acid methyl ester, 3-pentafluoroethyl-2-methylacrylic acid methyl ester, 3-diphenyl-3-methyl-2-fluoroacrylic acid methyl ester, 2,3,3-trimethylacrylic acid butyl ester, 3 -Phenyl-3-methyl-2-chloroacrylic acid t-butyl ester, 3-phenyl-3-methylthiomethyl-2-fluoroacrylic acid methyl ester and the like can be mentioned.

The other raw material used in the present invention is halogen. Examples of the halogen include fluorine, chlorine, bromine and iodine, and chlorine and bromine are particularly preferably used.

The tertiary amine or tertiary phosphine used in the present invention exerts a catalytic action in the reaction between the raw materials. The tertiary amine or tertiary phosphine is not particularly limited, and known compounds can be used. Specific examples of tertiary amines that are particularly preferably used include trimethylamine, triethylamine, tripropylamine, tributylamine, pyridine, and pyrazine. Above all, triethylamine and pyridine are preferably used because they are easy to handle. Specific examples of the tertiary phosphine which is particularly preferably used include trimethylphosphine, triethylphosphine, triphenylphosphine and the like. Above all, triethylphosphine and triphenylphosphine are preferably used because they are easy to handle.

In the production of the dihalogenopropionic acid ester according to the present invention, the reaction can be carried out in the absence of a solvent, or the reaction can be carried out in an inert organic solvent. The inert organic solvent is not particularly limited, and a known inert organic solvent can be applied. Specific examples of inert organic solvents that are particularly preferably used include methylene chloride, methylene bromide, chloroform, carbon tetrachloride, dichloroethane, trichloroethane, and other halogenated hydrocarbon solvents; methanol, ethanol, propanol, and the like. Alcohol solvents; aromatic solvents such as benzene, toluene, xylene; saturated aliphatic solvents such as pentane, hexane, heptane; ether solvents such as diethyl ether, dibutyl ether, dimethoxyethane, diethylene glycol dimethyl ether, tetrahydrofuran, etc. To be

In carrying out the present invention, when the acrylic acid ester has a high polymerizability, it is a preferred embodiment to add a polymerization inhibitor and carry out the reaction. Specific examples of the polymerization inhibitor include hydroquinone, hydroquinone monomethyl ether, and t.
-Butylcatechol and the like can be mentioned.

In carrying out the present invention, the procedure of the reaction operation, that is, the order of adding the acrylic ester, the halogen, the polymerization inhibitor, the inert organic solvent and the tertiary amine or tertiary phosphine is not particularly limited. Usually, acrylic acid or a derivative thereof, a polymerization inhibitor and a tertiary amine or a tertiary phosphine are prepared in an inert organic solvent, and halogen is blown into or dripped into the solvent, or a predetermined amount of halogen is added. It is advisable to add a solution prepared by dissolving in an inert solvent.

The molar ratio of acrylic acid ester and halogen used in the present invention is not particularly limited, but generally 1: 0.1 to.
It is suitable to use a molar ratio of 1: 100, preferably 1: 1.0 to 1:10.

Further, the amount of the tertiary amine or tertiary phosphine used is not particularly limited and may be appropriately determined as necessary, but generally 0.01 to 80 mol%, preferably 1 to 40 mol% based on the acrylic ester. It is preferred to choose from the range of percentages.

When a polymerization inhibitor is used, it is preferable to select the polymerization inhibitor in the range of 0.01 to 80 mol%, preferably 1 to 40 mol% based on the acrylic acid ester.

Furthermore, when using an inert organic solvent, the weight ratio of acrylic ester to inert solvent is generally from 1: 1 to 1: 2.
It is preferable to select 0, preferably 1: 1 to 1: 8.

The reaction temperature in the present invention is not particularly limited and can be selected in a wide temperature range, but it is generally preferred to select from the range of -70 ° C to 100 ° C, preferably the range of -20 ° C to 50 ° C. Also,
The reaction time varies depending on the reaction conditions, but is usually 2 to 20 hours,
It is preferably 4 to 12 hours.

The method for purifying the dihalogenopropionic acid or its derivative obtained in the present invention is not particularly limited. Generally, after adding the reaction solution to water, extraction with an inert solvent such as benzene, toluene, methylene chloride, chloroform, carbon tetrachloride, ether, etc., drying, and atmospheric distillation, reduced pressure distillation, recrystallization, or chromatography. It can be purified by E.

〔effect〕

INDUSTRIAL APPLICABILITY The present invention can produce a dihalogenopropionic acid ester in a high yield and with good selectivity.

The present invention will be described with reference to Reference Examples and Examples in order to more specifically describe the present invention, but the present invention is not limited to these Examples.

Reference example A 200 ml-brown three-necked flask equipped with a stirrer, 86.09 g of acrylic acid methyl ester, 21.3 g of disodium hydrogen phosphate.
And 0.1 g of hydroquinone were added, and the mixture was placed in a warm bath at 10 ° C. Chlorine gas was bubbled at 55 ml / min for 7 hours under stirring in a nitrogen atmosphere, and the mixture was further stirred for 1 hour. Subsequently, the reaction solution was distilled under reduced pressure, but the target 2,3-dichloropropionic acid methyl ester was obtained only in an isolated yield of about 80%. In fact, when the reaction mixture solution was measured with packing material SE-30 (trade name) and a column temperature of 70 ° C, only the peak of 2,3-dichloropropionic acid methyl ester, which was the target substance, was observed. When measured at a temperature of 170 ° C,
Further chlorinated products 2,2,3-trichloropropionic acid methyl ester and 2,2,3,3-tetrachloropropionic acid methyl ester are the desired product 2,3-dichloropropionic acid methyl ester 10 Against 2, respectively
It was generated at a rate of 1.

Example 1 86.09 g of acrylic acid methyl ester, 1.63 g of pyridine and 0.1 g of hydroquinone were added to a 200 ml-brown three-necked flask equipped with a stirrer, and the mixture was placed in a 30 ° C. warming bath. In a nitrogen atmosphere, chlorine gas was bubbled at a rate of 55 ml / min for 7 hours with stirring, and then the mixture was further stirred for 1 hour. Then, by distilling the reaction solution under reduced pressure, 156.1 g of 2,3-dichloropropionic acid methyl ester (boiling point 80 ° C./30 mmHg), which is a target substance,
Obtained in a yield of 99.4%.

Example 2 In the same manner as in Example 1, 121 g of 2-chloroacrylic acid methyl ester, 1.52 g of triethylamine and hydroquinone
Chlorine gas was blown in the presence of 0.1 g to cause a reaction. After the same treatment, 113.9 g of the target product, 2,3,3-trichloropropionic acid methyl ester (boiling point 90 ° C./27 mmHg), was obtained at a yield of 99.1%.

Example 3 In the same manner as in Example 1, chlorine gas was reacted by blowing chlorine gas in the presence of 114 g of 3-methylacrylic acid ethyl ester, 3.93 g of triphenylphosphine, 0.1 g of hydroquinone and 100 ml of methanol. Subsequently, methanol was distilled off under reduced pressure, water was added, and the mixture was extracted with chloroform. The chloroform layer was dried and evaporated under reduced pressure to obtain 2,3-
Dichlorobutyric acid ethyl ester was obtained with a yield of 99.5%.

Example 4 To a 500 ml-brown three-necked flask equipped with a stirrer, 148 g of acrylic acid phenyl ester, 1.77 g of triethylphosphine, 0.1 g of hydroquinone and 200 ml of carbon tetrachloride were added, and the mixture was placed in a 30 ° C warming bath. Under stirring in a nitrogen atmosphere, 160 g of bromine was gradually added dropwise. The reaction was stopped 5 hours after the dropping. The reaction solution was washed with water, dried and evaporated under reduced pressure to obtain the desired 2,3-dibromopropionic acid phenyl ester with a purity of 99.5% and a yield of 99.3%.

Example 5 Using the raw materials, halogen, catalyst and solvent shown in Table 1,
Dihalogenopropionic acid or a derivative thereof was synthesized in the same manner as in Example 1 under the reaction conditions shown in Table 1. The yields of the resulting products are also shown in Table 1.

Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location // B01J 31/02 X 8017-4G 102 X 8017-4G C07B 61/00 300

Claims (1)

[Claims] 1. A general formula (1) (However, R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and R ₄ represents a substituted or unsubstituted alkyl group, a substituted or non-substituted A substituted phenyl group is represented by the formula) and a halogen are reacted in the liquid phase in the presence of a tertiary amine or a tertiary phosphine. (However, R ₁ , R ₂ , and R ₃ are a hydrogen atom, a halogen atom,
A substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, R ₄ represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and X represents a halogen atom. ) A method for producing a dihalogenopropionic acid ester represented by: