JPS636547B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved process for producing α-chloro-β-phthalimidopropionitrile. More specifically, when producing α-chloro-β-phthalimidopropionitrile from phthalimide and α-chloroacrylonitrile,
The present invention relates to a method for producing α-chloro-β-phthalimidopropionitrile, characterized in that the reaction is carried out in an organic solvent in the presence of a catalytic amount of an alkali metal salt or alkaline earth metal salt of phthalimide.

Compound α-chloro-β obtained by the method of the present invention
- Phthalimidopropionitrile is a compound useful as an intermediate for amino acids or pharmaceuticals.
Originally, the method for producing α-chloro-β-phthalimidopropionitrile was to drop a catalytic amount of a methanol solution of sodium methoxide into a mixture of 1 molar ratio of phthalimide and 7.5 molar ratio of α-chloroacrylonitrile. How to manufacture (K.
D. Gundermann, chem. Ber., vol. 91, p. 160 (1958)). According to the above literature, when α-acrylonitrile is used in approximately the same molar amount as phthalimide, the main product is α-chloro-β-[2-carbomethoxybenzoylamino]propionitrile with the phthalimide ring opened. It is stated that it is given.

In this way, α-chloro-β by the above-mentioned known method
- In the production method of phthalimidopropionitrile (1)
A large excess of α-chloroacrylonitrile is required relative to phthalimide, and (2) during the reaction, a compound with an opened phthalimide ring is produced by the action of a base and methanol. (3) When α-chloroacrylonitrile comes into contact with strong basic substances such as sodium methoxide, side reactions such as polymerization and decomposition are accelerated.
In the known method, although the method of adding the base dropwise has been devised, there are problems such as partial polymerization and decomposition of α-chloroacrylonitrile, resulting in the reaction solution becoming extremely colored.

As described above, the known methods have various problems and cannot be said to be a production method that is necessarily satisfactory from an industrial standpoint.

The present inventors have intensively investigated an industrially advantageous production method for α-chloro-β-phthalimidopropionitrile, and found that phthalimide and α-chloroacrylonitrile are mixed in an organic solvent with a catalytic amount of an alkali metal salt of phthalimide or The present invention was accomplished by discovering that α-chloro-β-phthalimidopropionitrile can be easily obtained in high yield by reacting it in the presence of an alkaline earth metal salt.

According to the method of the present invention, side reactions such as polymerization and decomposition of the raw material α-acrylonitrile itself and by-products of compounds with opened phthalimide rings are significantly suppressed, and α-chloro-β-phthalimidopropi This method not only improves the yield of nitrile, but also significantly reduces the amount of α-acrylonitrile used relative to the raw material phthalimide, and has the advantage that no special measures are required for the reaction operation. That is, the method of the present invention is a much superior and industrial method for producing α-chloro-β-phthalimidopropionitrile compared to known methods.

In the method of the present invention, α-chloroacrylonitrile and phthalimide are used as raw materials.
The amount of these raw materials used is 1 to 3 moles of α-chloroacrylonitrile per 1 mole of phthalimide.
Preferably it is 1.05 to 2 mol.

Further, in the method of the present invention, the reaction is carried out in an organic solvent, and the organic solvents used include methanol, ethanol, n-propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, methyl cellosolve, cellosolve, Alcohols such as glycerin, hydrocarbons such as benzene, toluene, xylene, cyclohexane, hexane, heptane, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane,
1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane,
Halogenated hydrocarbons such as tetrachloroethylene, chlorobenzene, o-dichlorobenzene, ethers such as dioxane, trioxane, tetrahydrofuran, ketones such as acetone, methyl ethyl ketone, esters such as ethyl acetate, butyl acetate, acetonitrile, nitrobenzene, N-methyl Formamide, N.N-dimethylformamide, N.N-diethylformamide, N-methylpyrrolidone, dimethylsulfoxide and the like can be mentioned. These solvents are usually used alone, but in some cases two or more solvents may be used in combination. The amount of the solvent used is at least 1 times the weight of phthalimide, preferably at least 2 times the weight in terms of reaction operation.

In the method of the present invention, an alkali metal salt or an alkaline earth metal salt of phthalimide is used as chlorine. Mention may be made, for example, of the lithium, sodium, potassium or calcium salts of phthalimide. The amount used is a catalytic amount. Specifically, it is used in a molar ratio of 0.005 to 0.4, preferably 0.01 to 0.2 molar relative to the raw material phthalimide. Although there is no problem in the reaction even if the amount is used above the upper limit of the above range, the above range is sufficient for practical purposes. Also, the amount used is higher than that of phthalimide.
If the molar ratio is less than 0.005, the reaction progresses extremely slowly and is not practical.

The reaction between phthalimide and α-chloroacrylonitrile in the method of the present invention is usually carried out by adding phthalimide and an alkali metal salt or alkaline earth metal salt of phthalimide to a solvent, and gradually adding α-chloroacrylonitrile dropwise while heating or cooling. and then 0 to 120°C for 0.5 to 10 hours, preferably
React at 30-100°C for 1-6 hours. The end point of the reaction can be easily and quickly determined by thin layer chromatography.

In the method of the present invention, the α-chloro-
In order to isolate β-phthalimidopropionitrile from the reaction solution, if the product has precipitated outside the system, the reaction solution may be separated as is, or the reaction solution may be concentrated and then separated. If the product is dissolved, an organic solvent that hardly dissolves the product is added, or the solvent is removed by steam distillation or the like and then separated.

Hereinafter, the present invention will be explained with reference to Examples.

Example 1 29.4 g of phthalimide, 3.2 g of phthalimidocaricum and hydroquinone in 88 g of methanol
Add 0.15g and heat to 50℃ while stirring.
- Add 21 g of chloroacrylonitrile dropwise at 50-55°C over approximately 1 hour. Thereafter, the mixture was reacted at the same temperature for 5 hours, and then cooled to 20 DEG C. to separate precipitated crystals, washed with a small amount of methanol and water, and dried to obtain white α-chloro-β-phthalimidopropionitrile.

Yield 40.3g (86% yield vs. phthalimide) Melting point (℃): 142-143 Elemental analysis value: C _{H 7} ClN ₂ O ₂ Calculated value (%) 56.31 3.01 15.11 11.94 Analysis value (%) 56.15 3.05 15.14 11.72 The end point of the reaction is determined by thin layer chromatography (thin layer plate; Tokyo Kasei Spot Film Silica Gel-F; developing solvent; benzene:acetone=
8:2 (volume ratio)), and a point was determined at which spots of phthalimide, the raw material, disappeared.

Example 2 The reaction was carried out in the same manner as in Example 1 except that 88 g of isopropanol was used instead of methanol.
39.6 g (84.4% yield vs. phthalimide) of α-chloro-β-phthalimidopropionitrile was obtained.

Example 3 In Example 1, 2.7 g of sodium phthalimide was used instead of potassium phthalimide, and the reaction was carried out in the same manner as in Example 1, resulting in 39.4 g (yield: 84% vs. phthalimide).
α-chloro-β-phthalimidopropionitrile was obtained.

Claims (1)

[Claims] 1. When producing α-chloro-β-phthalimidopropionitrile from phthalimide and α-chloroacrylonitrile, phthalimide and a catalytic amount of an alkali metal salt or alkaline earth metal salt of phthalimide are added to an organic solvent, and then α- A method for producing α-chloro-β-phthalimidopropionitrile, which comprises adding chloroacrylonitrile and causing the reaction.