JPS61277663A - Method for stabilizing aziridine-2-carboxamide - Google Patents

Abstract

PURPOSE:To stabilize aziridine-2-carboxamide, by adding a stabilizer selected from alkali (earth) metal hydroxides, ammonia and organic amines to a solution containing the aziridine-2-carboxamide having an ammonia concentration of a specific value or below. CONSTITUTION:A stabilizer consisting of a base is added to a solution con taining aziridine-2-carboxamide (A) having <=0.1wt% ammonia concentration to allow the compound (A) to stand under a more basic atmosphere than the basicity thereof and stabilize the compound (A). The above-mentioned stabilizer is at least one selected from hydroxides, carbonates, phosphates, etc., of alkali (earth) metals, ammonia and organic amines ammonia and tertiary amine are particularly preferred. EFFECT:The deterioration can be prevented in a reaction process requiring heating or storage or transportation in a large amount or for a long period. USE:An antitumor agent, intermediate for agricultural chemicals, raw material for functional resins, etc.

Description

BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a method for stabilizing aziridine-2-carboxylic acid amides.

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.

Problems to be Solved by the Invention Aziridine-2-carboxylic acid amide is a very unstable compound, and in particular, it cannot be subjected to reaction operations, stored or transported in acidic or neutral conditions or in heated conditions. etc., resulting in deterioration and a significant decrease in purity.
There is a problem.

In particular, deterioration due to cleavage of the aziridine ring may proceed in a chain manner, 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 adding an alkali such as caustic soda increases the stability against polymerization.
There are no reports regarding the stabilization of 2-carboxylic acid amides.

Therefore, the present inventors investigated various ways to suppress the deterioration of aziridine-2-carboxylic acid amide and increase its stability. We have completed the present invention by discovering that by bringing the material into a basic atmosphere, 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 involves adding a stabilizer consisting of a base to a liquid containing aziridine-2-carboxylic acid amide with an ammonia concentration lower than 0.1% by weight. This method is characterized by bringing the 2-carboxylic acid amide into a more basic atmosphere than the basicity of the 2-carboxylic acid amide.

Effects The method of the present invention is extremely effective in preventing deterioration of aziridine-2-carboxylic acid amide during reaction steps that require heating such as concentration and purification, and during long-term storage and transportation, and has industrial value. Extremely large.

In general, it is known that aziridine ring compounds cause isomerization or ring-opening reactions with ammonia and organic amines (Japan Chemical Industry Association Monthly Report May 1984 issue p.
, 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 aziridine-2-carboxylic acid amide to be stabilized in the present invention is one that is present in a reaction process that involves heating such as concentration and purification, or one that is being stored or transported for a long time or is in a state of ammonia. Concentration is 0.11%
It is in the form of a lower (including 0) solution. Here, the ammonia is usually derived from the ammonia used in the above-mentioned typical production method.

Stabilizer Compound In the present invention, a base is used as a stabilizer. Specifically, (a) hydroxides, carbonates, phosphates, borates of alkali metals and alkaline earth metals;
and acetate, (b) ammonia, and (c) organic amine, or a combination of two or more thereof.

Hydroxides of alkali metals and alkaline earth metals include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, beryllium hydroxide, magnesium hydroxide, calcium hydroxide, and water. Strontium oxide, barium hydroxide, etc. Carbonates include lithium carbonate, sodium carbonate, potassium carbonate, sodium potassium carbonate, rubidium carbonate, cesium carbonate,
Magnesium carbonate, calcium carbonate, calcium magnesium carbonate, strontium carbonate, barium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. Phosphates include lithium phosphate, lithium dihydrogen phosphate, sodium phosphate, etc. , sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, magnesium phosphate, magnesium hydrogen phosphate, calcium phosphate, calcium hydrogen phosphate, dihydrogen phosphate hydrogen calcium,
Strontium phosphate, sudrontiram hydrogen phosphate,
Examples of borates include barium phosphate, barium hydrogen phosphate, barium dihydrogen phosphate, lithium borate, sodium borate, potassium borate, magnesium borate,
Examples of acetate salts such as calcium borate and barium borate include lithium acetate, sodium acetate, potassium acetate, rubidium acetate, cesium acetate, magnesium acetate, calcium acetate, strontium acetate, and barium acetate. In addition, organic amines include methylamine, dimethylamine, trimethylamine, ethylamine,
diethylamine, triethylamine, propylamine,
Diethylamine, 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-methylhexamethyleneimine, N-hexylhexamethyleneimine, pipecoline,
N-methylbibecolin, 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, trioctylamine, 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 0.0001 times the weight of aziridine-2-carboxylic acid amide, and the greater the amount, the greater the stabilizing effect.

However, as a matter of course, the effectiveness of the stabilizer has its own limits, and even if it is used too frequently, the effect will not necessarily be proportional to its effectiveness. 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, taking into consideration the usage conditions and the stabilizing effect.

Therefore, in reality, when the stabilizer is (1) ammonia and (3) organic amine, the amount is 0.0001f!
Weight times, preferably o, ooi times weight to 10 times weight,
More preferably, it is used in a range of 0.01 times by weight 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 by weight;
Preferably 0.001 to 1 times by weight, more preferably 0
．． 1 is used in the range of 01 to 0.5fffffi times.

As for the method of adding the stabilizer, in the present invention, aziridine-
Since 2-carboxylic acid amide exists in a solution state in water, alcohols such as methanol and ethanol, and other solvents that can dissolve aziridine-2-carboxylic acid amide, it is safe to use there. -2-carboxylic acid amide 3. Og to water 60-
and placed in a 200d flask.

0.3 SF of N-methylpiperidine was added thereto, and water was distilled off from this solution using a rotary evaporator under reduced pressure of 30MHQ on a 50°C hot bath for 7 hours.

When the residue at this time was analyzed by liquid chromatography, the residual rate of aziridine-2-carboxylic acid amide was 99.0%. Comparative Example 4 Aziridine-2-carboxylic acid amide 3. Og to water 60-
The solution was dissolved in water, placed in a 200 d flask, and water was distilled off in the same manner as in Example 8. When the remaining solid was analyzed, the residual rate of aziridine-2-carboxylic acid amide was 89.
．． It was 8%.

Claims (1)

[Claims] 1. A stabilizer consisting of a base is added to a solution containing aziridine-2-carboxylic acid amide with an ammonia concentration lower than 0.1% by weight to make the aziridine-2-carboxylic acid amide less basic. A method for stabilizing aziridine-2-carboxylic acid amide, which is characterized in that the aziridine-2-carboxylic acid amide is brought into a strongly basic atmosphere. 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. Method according to claim 2, in which the stabilizer is at least one selected from ammonia and organic amines; 4, in which the stabilizer is tertiary amines; claim 3, in which the stabilizer is a tertiary amine.
The method described in section.