JPS62228055A - Production of aziridine-2-carboxylic acid barium salt - Google Patents

Abstract

PURPOSE:To obtain the titled substance in high yield at a low cost with single step process, by reacting 2,3-dihalopropionic acid derivative or alpha-haloacrylic acid derivative with ammonia in an aqueous medium in the presence of Ba(OH)2. CONSTITUTION:The titled substance can be produced by reacting (A) a 2,3- dihalopropionic acid derivative of formula I or an alpha-haloacrylic acid derivative of formula II (X is halogen; Y is -CO2R<1>, -CONR2<2> or -CN; R<1> is 1-10C hydrocarbon residue; R<2> is H or 1-10C hydrocarbon residue) with (B) 2-50mol of ammonia based on 1mol of the substrate in an aqueous medium in the presence of Ba(OH)2 at 50-150 deg.C for 30min-50hr. The molar ratios of Ba(OH)2 to the compound of formula I and the compound of formula II are preferably >=1.5 and >=1, respectively. The aqueous medium is water or a mixture of water and an organic solvent (e.g. methanol). USE:An intermediate for pharmaceuticals, agricultural chemicals, alpha-amino acids, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to a method for producing barium salt of aziridine-2-carboxylic acid. More specifically, the present invention relates to a method for producing aziridine-2-carboxylic acid barium salt from a 2,3-dihalopropionic acid derivative or an α-haloacrylic acid derivative.

Aziridine-2-carboxylic acid barium salt is a compound useful as an intermediate for pharmaceuticals, agricultural chemicals, α-amino acids such as serine, and the like.

BACKGROUND ART The following methods are known as methods for producing metal salts of aziridine-2-carboxylic acid.

(1) 2.3-Dibromopropionic acid ester is reacted with liquid ammonia, and the resulting aziridine-2-carboxylic acid ester is reacted with an alkali metal or alkaline earth metal hydroxide in water to produce aziridine-2-carboxylic acid ester. Method for producing acid salts (E, Kyburz et al., H
e1v, Chim, ACta 49 (1)
.

359 (1966), K. D. Gunderm
ann et al.: Chem, Ber, 93°1632
(1960), ) (2> α-halo β-aminopropionitrile or its mineral acid salt is reacted with an alkali metal or alkaline earth metal hydroxide in water or a water-containing organic solvent to produce aziridine-2-carboxylic acid. Method for producing acid salts (JP-A-56-8
Publication No. 3470).

(3) 2.3-dihalopropionitrile or α-
Acrylonitrile is reacted with ammonia in water or a water-containing organic solvent to form α-8 to β-aminopropionitrile, which is then subsequently reacted with an alkali metal or alkaline earth metal hydroxide without mixing. A method for producing aziridine-2-carboxylate by
No. 6-90055, No. 56-100759).

However, although these methods have some value, they seem to have some problems. That is, method (1) not only has a low yield of aziridine-2-carboxylic acid ester, but also has a low yield of aziridine-2-carboxylic acid ester.
Since the carboxylic acid ester itself is an unstable compound, the recovery rate in purification steps such as distillation is low, and it cannot be said that this is an industrially advantageous method. Method (2) is difficult to handle industrially because α-octahe-β-aminopropionitrile is an unstable compound. In order to handle this compound stably, it must be in the form of a mineral acid salt, and the process is extremely complicated. Although method (3) has somewhat improved the drawbacks of (2), since α-8he-β-aminopropionitrile is an unstable compound, it is necessary to continue immediately after the formation of this compound. It is necessary to add an alkali metal or alkaline earth hydroxide, and it must be said that there are considerable problems in carrying out such an operation industrially.

As mentioned above, it cannot be said that the method for producing aziridine-2-carboxylic acid barium salt has necessarily been completed industrially.

[Summary of the invention]

Summary The present inventors have discovered that from a 2,3-dihalopropionic acid derivative or an α-haloacrylic acid derivative, in one reaction operation,
Furthermore, as a result of extensive research into a method for producing the desired aziridine-2-carboxylic acid salt in high yield, the present invention was achieved.

That is, the method for producing barium salt of aziridine-2-carboxylic acid according to the present invention is a method for producing barium salt of aziridine-2-carboxylic acid.
- reacting a dihalopropionic acid derivative or an α-haloacrylic acid derivative represented by general formula (II) with ammonia in the presence of calcium hydroxide in an aqueous medium;
It is characterized by:

X II XCH2CH-Y CH2=C-Y (I) (II) (where, Hydrocarbon residue having 1 to 10 carbon atoms, R2
is a hydrogen atom or a hydrocarbon residue having 1 to 10 carbon atoms. ) Effects In the present invention, the desired barium salt of aziridine-2-carboxylic acid can be produced from the raw material 2,3-dihalopropionic acid derivative or α-haloacrylic acid derivative in one operation and in high yield. Therefore, the reaction operation is simple, the reaction apparatus can be simplified, and it is therefore economical.

What is noteworthy about the present invention is that the alkali is limited to barium hydroxide. For example, even when sodium hydroxide is used in place of barium hydroxide, the yield of aziridine-2-carboxylic acid sodium salt is surprisingly low (see Comparative Examples 1 and 2).

In the present invention, we will explain the reason why such a difference occurs depending on the type of alkali and how barium salt of aziridine-2-carboxylic acid can be prepared from a 2,3-dihalopropionic acid derivative or an α-8 acrylic M derivative in one step. The mechanism by which this occurs is unknown.

As described above, there is no conventional method for producing aziridine-2-carboxylate from a 2,3-dihalopropionic acid derivative or an α-haloacrylic acid derivative in a single reaction.
Moreover, the fact that aziridine-2-carboxylate can be obtained in high yield only when the alkali used in this reaction is barium hydroxide cannot be inferred from conventionally known techniques, and must be called an unexpected discovery. .

[Detailed description of the invention]

The process for producing aziridine-2-carboxylic acid salts according to the invention consists of the reaction of a specific C3-carboxylic acid derivative with an alkali in an aqueous medium.

The 2,3-shiba[1 propionic acid derivative and α-haloacrylic acid derivative used in the present invention are represented by the above-mentioned formula (I) and formula (II). In the formula, X is preferably chlorine or bromine, and from the economic point of view, chlorine is particularly preferred. As R1 (C1 to C1o), a hydrocarbon residue having preferably 1 to 5 carbon atoms, particularly preferably 1 to 3 carbon atoms is suitable.

R2 (H or C1 to C1o) is preferably a hydrogen atom or a hydrocarbon residue having 1 to 3 carbon atoms, and particularly preferably a hydrogen atom.

These 2,3-dihalopropionic acid derivatives and α-
Examples of haloacrylic acid derivatives are as follows.

2.3~Methyl dichloropropionate, ethyl 2,3-dichloropropionate, 2,3-dichloropropion 1
ln-propyl, 2,3-dic[10i-propyl pionate, butyl 2,3-dichloropropionate, 2.3-
amyl dichloropropionate, octyl 2,3-dichloropropionate, decyl 2,3-dichloropropionate, phenyl 2,3-dichloropropionate, benzyl 2,3-dichloropropionate, naphdyl 2,3-dichloropropionate, 2,3-dichloropropionic acid amide, 2,3-dichloropropionic acid-N-methylamide,
2,3-dichloropropionic acid-N,N-dimethylamide, 2,3-dichloropropionic acid-N-edylamide, 2,3-dichloropropionic acid-N,N-diethylamide, 2,3-dichloropropionic acid-N -Propylamide, 2,3-dichloropropionic acid-N,N-dipropylamide, 2,3-dichloropropion M-N-amylamide, 2,3-dichloropropionic acid-N-ocdylamide, 2,3-dichloropropion Acid-N-decylamide, 2,3-dichloropropionitrile, α-methyl chloroacrylate, α-ethyl chloroacrylate, α
-propyl chloroacrylate, α-butyl chloroacrylate, α-amyl chloroacrylate, α-hexyl chloroacrylate, α-octyl chloroacrylate, α-cyclohexyl chloroacrylate, α-decyl chloroacrylate, α- Phenyl chloroacrylate, α-naphthyl chloroacrylate, α-chloroacrylamide, α-chloro-N-methylacrylamide, α-chloro-N,N
-diethylacrylamide, α-chloro-N~ethylacrylamide, α-chloro-N,N-diethylacrylamide, α-chloro-N-propylacrylamide, α
-Chloro-N,N-dipropylacrylamide, α-chloro-N-butylacrylamide, α-chloro-N-hexylacrylamide, α-chloro-N-decylacrylamide, α-chloro-N-phenylacrylamide,
α-chloro-N-naphdylacrylamide, α-chloroacrylonyl-1-lyl, and compounds in which chlorine in these compounds is replaced with fluorine, bromine, or iodine, etc.

Examples of preferred compounds among these include methyl 2.3-dichloropropionate, ethyl 2,3-dichloropropionate, n-propyl 2,3-dichloropropionate, and i-propyl 2,3-dichloropropionate. ,2,
Butyl 3-dichloropropionate, amyl 2,3-dichloropropionate, 2,3-dichloropropionamide, 2゜3-dichloropropionate-N-methylamide, 2,3-dichloropropion M-N, N-dimethyl Amide, 2,3-dichloropropionic acid-N-ethylamide, 2,3-dichloropropionic acid-N,N-diethylamide, 2,3-dichloropropionic acid-N, 2,3-dichloropropionic acid-N-propylamide, 2,3-dichloropropionic acid-N , N-dipropylamide, 2゜3-dichloropropionitrile,
α-Methyl chloroacrylate, α-ethyl chloroacrylate, α-propyl chloroacrylate, α-butyl chloroacrylate, α-amyl chloroacrylate, α-chloroacrylamide, α-chloro1]-N-methylacrylamide , α-chloro-N-ethylacrylamide, α-
Chloro-N,N-dimethylacrylamide, α-chloro-N-ethylacrylamide, α-chloro-N,N-diethylacrylamide, α-chloro-N-propylacrylamide, α-chloro-N,N-dipropylacrylamide, Examples include α-chloroacrylonitrile, and compounds in which chlorine in these compounds is replaced with bromine.

Further, particularly preferred examples include methyl 2,3-dichloropropionate, ethyl 2,3-dichloropropionate, n-propyl 2,3-dichloropropionate, 2,3-dichloropropionate,
-dichloropropionic acid amide, 2,3-dichloropropionitrile, α-methyl chloroacrylate, α-ethyl chloroacrylate, α-propyl chloroacrylate,
Examples include α-chloroacrylamide and α-chloroacrylonitrile.

All of these are known compounds, and those produced by a suitable method can be used as raw materials for the present invention.

Aqueous Medium The reaction medium used in the present invention is an aqueous medium, ie, water or a mixed solvent of water and an organic solvent.

Organic solvents that may be used in combination with water include alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, ethylene glycol, and cellosolve, dioxane, and tetrahydrofuran. , diethyl ether, diisopropyl ether, and hydrocarbons such as acetone, N,N-dimethylformamide, dimethyl sulfoxide, hexane, toluene, and xylene.

Among these, methanol, ethanol, i-propertool, etc. are preferred. The amount of water contained in these organic solvents is determined by the amount of water contained in 2,3-dihalopropionic acid derivatives or α
- Acrylic fi to eight! It is optional as long as the amount is 2 moles or more per mole of the derivative.

Among these solvents, water alone is particularly preferred.

The amount of the aqueous medium used is usually 0.1 to 50% by weight of the 2,3-dihalopropionic acid derivative or α-88acrylic acid derivative (hereinafter referred to as substrate), preferably 1 to 50% by weight. The amount corresponds to about 20% by weight.

Reaction Conditions In practicing the present invention, barium hydroxide is used as a 2,3-dihalopropion i! 1!2 Normally 1 mol or more, preferably 1.5 mol or more, α
- It is usually 0.8 mol or more, preferably 1 mol or more per 1 mol of haloacrylic acid derivative. There is no particular upper limit on the amount of barium hydroxide used, but the ease of stirring,
From an economical point of view, the amount is usually 50 mol or less, preferably 10 mol or less, per 1 mol of the substrate.

The amount of ammonia used is usually 1 mol or more, preferably 2 mol or more, per 1 mol of the substrate.

There is no upper limit to the amount of ammonia used, but from equipment and economical standpoints, it is usually 10
It may be about 0 mol or less, preferably 50 mol or less.

Any suitable combination of reaction temperature and reaction time can be selected. For example, 10 minutes to 100 at 0 to 200℃
time, preferably 30 minutes to 50 hours at 50 to 150°C,
It is possible to select a combination V such as

EXPERIMENTAL EXAMPLES In the following experimental examples, raw materials and products were analyzed using gas chromatography 1 to graphite and high performance liquid chromatography.

Example 1 In a 200-liter flask equipped with a reflux condenser, 92z of 12.5% ammonia water (lower mmol as NH3) and barium hydroxide/Yagiwado (Ba(OH)/8H20) were added.
Add 22.5 g (67.6 mmol) of 2,3-dichloropropionitrile and 4.28 g (33.8 mmol) of 2,3-dichloropropionitrile.
was added and reacted at 80°C for 2 hours. When the reaction solution was analyzed, the yield of aziridine-2-carboxylic acid barium salt was 83.2%.

Example 2-1 2.3-Dichloropropioni-1-lyl was added to various raw materials 33
．． Example 1 was repeated substituting 8 mmol. The results were as shown in Table 1.

= 15- Example 20 Instead of ammonia water, 12.5% ammonia water 92
Example 1 using 90g of methanol added to
repeated. The yield of aziridine-2-carboxylic acid barium salt was 78.5%.

Comparative Example 1 Barium hydroxide to sodium hydroxide 135.2 mmo
Example 1 was repeated substituting I. The yield of aziridine-2-carboxylic acid sodium salt was only 42.3%.

Comparative Example 2 1 to 135.2 mmo of barium hydroxide hydroxide
Example 14 was repeated substituting I. Aziridine-2
-The yield of carboxylic acid thorium salt was only 38.7%.

Claims (1)

[Claims] 1. A 2,3-dihalopropionic acid derivative represented by the general formula (I) or an α-haloacrylic acid derivative represented by the general formula (II) is treated with barium hydroxide in an aqueous medium. Process for producing barium salt of aziridine-2-carboxylic acid, characterized by reaction with ammonia in the presence of ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (Here, X is a halogen atom selected from fluorine, chlorine, bromine, and iodine, and Y is -CO_2R^1, -CO
Each represents an atomic group selected from NR^2_2 and -CN. However, R^1 is a hydrocarbon residue having 1 to 10 carbon atoms, and R^2 is a hydrogen atom or a hydrocarbon residue having 1 to 10 carbon atoms. 2. The method according to claim 1, wherein X is chlorine.