JPS61277664A - Method for stabilizing aziridine-2-carboxamide - Google Patents

Abstract

PURPOSE:To prevent the deterioration in storage and transportation in a large amount or for long period, by adding a stabilizer selected form alkali (earth) metal hydroxides, etc., ammonia and organic amines to aziridine-2-carboxamide in the solid state. CONSTITUTION:A stabilizer consisting of a base is added to aziridine-2-car boxamide (A) in the solid state to allow the compound (A) in a more basic atmosphere than the basicity thereof. Thus, the compound (A) is stabilized. The above-mentioned stabilizer is selected from hydroxides, carbonates, phosphates, etc. of alkali (earth) metals, ammonia and organic amines, and ammonia and tertiary amines are preferred. The stabilizer is added by adding a solution thereof to a solvent, in which the stabilizer compound is soluble and the compound (A) is insoluble, or introducing gaseous ammonia into a container containing the compound (A). USE:An antitumor agent, intermediate for agricultural chemicals, raw material for functional resins, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for stabilizing aziridine-2-carboxylic acid amides present in the solid state.

Aziridine-2-carboxylic acid amide itself and its derivatives are compounds that have antitumor and other physiological activities, and are also useful compounds as reagents, agricultural chemicals, intermediates such as amino acids, and raw materials for functional resins, etc. be.

The loasiridine-2-carboxylic acid amide that the present invention aims to solve is a very unstable compound, and it is particularly difficult to perform reaction operations, store or transport it in acidic or neutral conditions or in heated conditions. There is a problem in that this causes deterioration in quality and a significant decrease in purity. In particular, deterioration due to cleavage of the aziridine ring may proceed in a chain reaction, which not only causes a decrease in purity but also may be dangerous in some cases.

Generally, in the case of aziridine (ethyleneimine), it is known that the stability against polymerization is increased by adding an alkali such as caustic soda, but aziridine-2-carboxylic acid, which exists in a solid state, There are no reports regarding the stabilization of acid amides.

Therefore, the present inventors investigated various methods for suppressing the deterioration of aziridine-2-carboxylic acid amide existing in a solid state and increasing its stability. The present invention was completed based on the discovery that by bringing acid amide into a more basic atmosphere than the acid amide, deterioration can be suppressed even at high temperatures and stability can be significantly increased.

Therefore, the method for stabilizing aziridine-2-carboxylic acid amide according to the present invention is to stabilize aziridine-2-carboxylic acid amide in the solid state.
The method is characterized in that a stabilizer consisting of a base is added to the carboxylic acid amide to bring the aziridine-2-carboxylic acid amide into a more basic atmosphere than the basicity of the aziridine-2-carboxylic acid amide.

Effects The method of the present invention is extremely effective in preventing deterioration of allydine-2-carboxylic acid amide present in a solid state during storage or transportation in large quantities or over long periods of time, and has extremely great industrial value.

In general, aziridine ring compounds are known to undergo isomerization or ring-opening reactions with ammonia and organic amines (Japan Chemical Industry Association Monthly Report May 1984 issue 1).
), 15), it must be said that the stabilizing effect of the present invention is truly surprising.

The aziridine-2-carboxylic acid amide to be stabilized in the present invention is a known compound.

This compound may be obtained by any method of preparation, but one such method is by reaction of 2,3-dichloropropionic acid ester or 2-chloroacrylic acid ester with ammonia. .

The reaction product obtained by such a method can be subjected to concentration, purification, etc. to obtain aziridine-2-carboxylic acid amide existing in a solid state, which is the object of the present invention.

The aziridine-2-carboxylic acid amide present in the solid state to be stabilized is particularly suitable in large quantities or during long-term storage or transportation.

1 Star Bunno 1 In the present invention, a base is used as a stabilizer. Specifically, selected from the group consisting of (a) hydroxides, carbonates, phosphates, borates, and acetates of alkali metals and alkaline earth metals, (b) ammonia, and (c) organic amines. or a combination of two or more of these.

Hydroxides of alkali metals and alkaline earth metals include lithium hydroxide, lithium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, beryllium hydroxide, magnesium hydroxide, calcium hydroxide, and water. Carbonates such as strontium oxide, barium hydroxide, etc.
Lithium carbonate, sodium carbonate, potassium carbonate, sodium potassium carbonate, rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, magnesium calcium carbonate, strontium carbonate, barium carbonate, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc., phosphoric acid As salts, lithium phosphate, lithium dihydrogen phosphate, sodium phosphate, sodium hydrogen phosphate,
Sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, magnesium phosphate, magnesium hydrogen phosphate, calcium phosphate,
Calcium hydrogen phosphate, calcium dihydrogen phosphate such as strontium phosphate, strontium hydrogen phosphate, barium phosphate, barium hydrogen phosphate, barium dihydrogen phosphate, etc. As borates, lithium borate, Acetate salts include sodium acid, potassium borate, magnesium borate, calcium borate, barium borate, etc.
Examples include rhidium acetate, sodium acetate, potassium acetate, rubidium acetate, cesium acetate, magnesium acetate, calcium acetate, strontium acetate, barium acetate, and the like. In addition, organic amines include methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, isopropylamine, diisopropylamine, triisopropylamine,
Butylamine, dibutylamine, tributylamine, isobutylamine, diisobutylamine, triisobutylamine, 2-ethylhexylamine, di(2-ethylhexyl)amine, tri(2-ethylhexyl)amine,
Octylamine, dioctylamine, trioctylamine, benzylamine, dibenzylamine, N,N-dimethylbenzylamine, piperidine, N-methylpiperidine, N-ethylpiperidine, N-propylpiperidine, hexamethyleneimine, N-methylhexane Methyleneimine, N-hexylhexamethyleneimine, pipecoline, N
-Methylpipecoline, N-ethylpipecoline, pyrrolidine, N-methylpyrrolidine, N-ethylpyrrolidine, N,
N,N',N'-tetramethylethylenediamine, N,N,N',N'-tetramethylhexamethylenediamine, pyridine, picoline, lutidine, collidine, monoethanolamine, jetanolamine, triethanolamine, etc. Can be mentioned.

Among these, preferred are ammonia and organic amines, and more preferred are ammonia, trimethylamine, triethylamine, tripropylamine, triisopropylamine, tributylamine, triisobutylamine, tri(2-ethylhexyl)amine, and trimethylamine. Octylamine, N, N-dimethylbenzylamine, N
-Methylpiperidine, N-propylpiperidine, N-methylhexamethyleneimine, N-ethylhexamethyleneimine, N-methylpipecoline, N-ethylpipecoline, N-methylpyrrolidine, N-ethylpyrrolidine, N
, N,N',N'-tetramethylethylenediamine, N,N,N',N'-tetramethylhexamethylenediamine, pyridine, picoline, lutidine, collidine, triethanolamine and the like.

The compounds exemplified above as stabilizers are readily available and are shown as practical representative examples, but the present invention is not necessarily limited to these.

The amount of these stabilizers used is at least 0,000 times as much as that of aziridine-2-carboxylic acid amide, and the greater the amount, the greater the stabilizing effect.

However, as a matter of course, the effect of the stabilizer has its own limits, and even if it is used too much, the effect will not necessarily be proportional to the amount. Also, in some cases, the presence of stabilizers can have an adverse effect, so in practice,
It is preferable to use the minimum necessary amount of aziridine-2-carboxylic acid amide in consideration of the usage situation and stabilizing effect.

Therefore, in practice, when the stabilizer is (b) ammonia and (c) an organic amine, it is o, oooi times to 100 times by weight, preferably 0 times by weight, relative to aziridine-2-carboxylic acid amide. It is used in an amount of 10 times by weight, preferably 0.01 times to 1 times by weight. On the other hand, when the stabilizer is (a) hydroxides, carbonates, phosphates, borates and acetates of alkali metals and alkaline earth metals, 0.0001 to 5 times the weight, preferably O ,,001 to 1 times by weight, more preferably 0
．． It is used in the range of 01 to 0.5ff1m times.

The stabilizer can be added by adding a solution of the stabilizer compound in a solvent in which the stabilizer compound is soluble and in which the aziridine-2-carboxylic acid amide is insoluble, or by adding a solution of the stabilizer compound dissolved in the aziridine-2-carboxylic acid amide. Gaseous ammonia or organic amine may be introduced into a container containing carboxylic acid amide.

There is no particular restriction on the applicable temperature range of the stabilizer used in the present invention. Adding a stabilizer is effective because aziridine-2-carboxylic acid amide undergoes deterioration even when the humidity is below v. Also, at high humidity of 50°C or higher, the deterioration of aziridine-2-carboxylic acid increases, so adding a stabilizer is effective. The effect of addition becomes greater.

Experimental Examples Example 1 Aziridine-2-carboxylic acid amide 3. Og to 10 (7
Place it in an Erlenmeyer flask, replace the inside of the container with ammonia gas, seal it tightly and let it stand at 30°C, and open it after 10 days.
When aziridine-2-carboxylic acid amide was dissolved in water and analyzed by liquid chromatography, the residual rate was 10
It was 0.0%.

100 m of 3°Og of aziridine-2-carboxylic acid amide
The mixture was placed in an Erlenmeyer flask, sealed tightly and allowed to stand at 30°C. 1
The bottle was opened after 0 days, and the aziridine-2-carboxylic acid amide was dissolved in water and analyzed using Liquid Chroma 1-Graphie, and the residual rate was 92.6%.

Example 1 was repeated except that trimethylamine gas was used instead of the IL ammonia gas. The residual rate of aziridine-2-carboxylic acid amide was 100%.

Example 3 Aziridine-2-carboxylic acid amide 3.
Added Og. Ether was distilled off from this slurry under reduced pressure at 91 to form a solid. This solid was placed in a 100 d flask, the flask was tightly stoppered, and the flask was left standing at 30°C. The residual rate of aziridine-2-carboxylic acid amide after 10 days was 98.
It was 1%.

Example 3 was repeated without using triethylamine. The residual rate of aziridine-2-carboxylic acid amide is 91.
It was 8%.

'LL! a4 0.1g of sodium hydroxide in 50d of dehydrated methanol
Add aziridine-2-carboxylic acid amide 3. Added Og. Methanol was distilled off from this solution at room temperature under reduced pressure to form a solid. This solid was placed in a 100 ml flask, the flask was tightly stoppered, and the flask was left standing at 30°C. The residual rate of aziridine-2-carboxylic acid amide after 10 days was 95.
It was 7%.

Comparative Example 3 Example 4 was repeated without using sodium hydroxide. The residual rate of aziridine-2-carboxylic acid amide is 90.
It was 3%.

Claims (1)

[Claims] 1. A stabilizer consisting of a base is added to aziridine-2-carboxylic acid amide existing in a solid state to form aziridine-2-carboxylic acid amide.
A method for stabilizing aziridine-2-carboxylic acid amide, which comprises bringing the 2-carboxylic acid amide into an atmosphere that is stronger than its basicity. 2. The stabilizer is from the group consisting of (a) hydroxides, carbonates, phosphates, borates and acetates of alkali metals and alkaline earth metals, (b) ammonia, and (c) organic amines. The method according to claim 1, which is at least one selected type. 3. The method according to claim 1, wherein the stabilizer is at least one selected from gaseous ammonia and organic amines.