Method for deuterating haloacrylic acid or its salt

Abstract

This invention provides a method for deuterating a haloacrylic acid or its salt with high efficiency on a commercial scale. The method is characterized in that a compound represented by general formula [1] wherein R<1> and R<2> each independently represent a light hydrogen atom or a heavy hydrogen atom, and at least one of R<1> and R<2> represents a light hydrogen atom; R<3> represents a light hydrogen atom, a heavy hydrogen atom, an alkali metal atom, or an alkaline earth metal atom; X represents a halogen atom; and n represents 1 or 2, is reacted with a heavy hydrogen source in the co-presence of a catalyst selected from palladium catalysts, platinum catalysts, rhodium catalysts, ruthenium catalysts, nickel catalysts, and cobalt catalysts not subjected to activation treatment. The deuterated compound is represented by general formula [2] wherein R<4> and R<5> each independently represent a light hydrogen atom or a heavy hydrogen atom, and at least one of R<4> and R<5> represents a heavy hydrogen atom; R<3> represents a light hydrogen atom, a heavy hydrogen atom, an alkali metal atom, or an alkaline earth metal atom; X represents a halogen atom; and n represents 1 or 2.

Description

technical field [0001] The invention relates to a method for deuterated hydrogenation of halogenated acrylic acid or its salt using a catalyst. Background technique [0002] Deuterated (deuterated and tritiated) compounds are believed to be useful in a variety of applications. For example, the compound after deuteration is very useful in analyzing the reaction mechanism and substance metabolism, and it is widely used as a labeling compound, and the stability and properties of the compound itself are changed due to the isotope effect, so the compound is considered as Pharmaceuticals, agricultural chemicals, organic EL materials, etc. are also useful. Furthermore, tritiated compounds are considered to be useful as labeling compounds for investigating the absorption, distribution, blood drug concentration, excretion, metabolism, etc. of pharmaceuticals and the like in animal experiments and the like. Therefore, in recent years, studies using deuterated (deuterated and tritiat...

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Problems solved by technology

[0007] 1) In the method of using deuterium peroxide to deuterate carboxylic acid under alkaline conditions, since the reaction solution is not neutral, complex purification operations are required for the separation of compounds deuterated by this method

[0008] 2) In the method of using the iridium complex that has not been activated as a catalyst, and using heavy water as a deuterium source to deuterate alcohols or carboxylic acids, there is a problem that the carbon atom that is bonded to the hydroxyl group in the carboxylic acid The farther the hydrogen atom is, the higher the hydrogenation rate of the hydrogen atom is, and the closer the hydrogen atom is to the hydroxyl group, the lower the hydrogenation rate of the hydrogen atom is, and, since the iridium complex itself used as a catalyst is unstable compounds, so it is difficult to manufacture and difficult to obtain

[0009] 3) When using palladium carbon without activation treatment as a catalyst, use KOD+D 2 The deuterium gas produced by the electrolysis of O is used as a deuterium source. In the method of deuterium hydrogenation of fatty acids, the production of deuterium gas requires special equipment, and its operation is very complicated and not practical.

In addition, in this method using deuterium gas as a deuterium source, it is difficult to deuterate compounds such as unsaturated fatty acids having unsaturated bonds that are easily reduced by hydrogenation

[0010] 4) Using a metal selected from Group 8 metals without activation treatment as a catalyst, using heavy water or a combination of heavy water and heavy hydrogen as a heavy hydrogen source, acrylic acid, methyl acrylate, methacrylic acid or methacrylic acid In the method of heavy hydrogenation of methyl ester, when only heavy water is used as heavy hydrogen source, there is the problem of low heavy hydrogenation rate, on the other hand, when using the combination of heavy water and heavy hydrogen gas as heavy hydrogen source, there is the following problem: heavy hydrogenation At the same time, the carbon-carbon double bond portion of acrylic acid, methyl acrylate, methacrylic acid or methyl methacrylate as the reaction substrate is easily hydrogenated (catalytic reduction) by deuterium gas, resulting in the inability to regenerate in the state of retaining the double bond. hydrogenation problem

[0011] 5) In the method of deuterating acrylic acid or methyl methacrylate using heavy water as a deuterium source using a catalyst that has not been activated, there is a problem of low deuterium rate

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