JPS61277665A - Method for purifying aziridine-2-carboxamide - Google Patents

Abstract

PURPOSE:To purify aziridine-2-carboxamide while preventing the deterioration thereof, by adding a stabilizer consisting of alkali (earth) metal hydroxide, etc., or ammonia to a solution of the aziridine-2-carboxamide and subjecting the resultant solution to a purification step. CONSTITUTION:A stabilizer consisting of a base selected from hydroxides, carbonates, phosphates, etc. of alkali (earth) metals and ammonia is added to a solution containing aziridine-2-carboxamide (A) to allow the compound (A) in a more basic atmosphere than the basicity thereof. Thus, the compound (A) is stabilized and then subjected to a purification step. The stabilizer is added by adding the the stabilizer to the compound (A) in the state of the solution thereof in water or another solvent to make the stabilizer present in the solution or suspension state. 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 purifying aziridine-2-carboxylic acid amide.

Aziridine-2-carboxylic acid amide itself and its derivatives are compounds that have antitumor and other physiological activities, and are also used as reagents! It is a compound useful as a raw material for a-drugs, intermediates such as amino acids, and functional resins.

While the present invention is intended to solve the problem, 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 and neutral conditions or in heated conditions. etc., resulting in deterioration and a significant decrease in purity.
There is a problem.

In particular, the alteration due to cleavage of the aziridine ring is 3! l! There is a possibility that the process progresses in a chain manner, and not only does it cause a decrease in purity, but it may also be dangerous in some cases.

When an aziridine-2-carboxylic acid amide solution is subjected to purification, heating is usually involved, so stabilization is an important issue in obtaining a purified product.

Conventional technology It is generally known that in the case of aziridine (ethyleneimine), the stability against polymerization is increased by adding an alkali such as caustic soda.
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 purifying aziridine-2-carboxylic acid amide according to the present invention involves adding (a) hydroxides, carbonates, and phosphates of alkali metals and alkaline earth metals to a solution containing aziridine-2-carboxylic acid amide. It is characterized by adding a stabilizer consisting of a base selected from the group consisting of boric acid, acetate, and (b) organic amines, and subjecting it to the purification step.

Effects The method of the present invention is extremely effective in preventing deterioration of aziridine-2-carboxylic acid amide during processes that require heating such as concentration and purification, and has extremely great industrial value.

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 according to the invention is the solution thereof to be purified.

Here, "purification" generally refers to aziridine-
This means increasing the depth of 2-carboxylic acid amide. A preferred embodiment of purification is the removal of coexisting impurities. Purification is usually carried out by distillation, extraction, etc. of the solution, but the effects of the present invention are particularly remarkable when coexisting impurities, solvents, etc. are removed by distillation accompanied by heating.

Stabilizer Compound In the present invention, a base is used as a stabilizer. Specifically, one selected from the group consisting of (a) hydroxides, carbonates, phosphates, borates, and acetates of alkali metals and alkaline earth metals, and (0) organic amines. Or a combination of two or more of these.

Alkali metal and alkaline earth metal hydroxides include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, beryllium hydroxide, magnesium hydroxide, calcium hydroxide, strontium hydroxide, Carbonates such as barium hydroxide include 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 hydrogen carbonate, carbonate. Sodium hydrogen, potassium hydrogen carbonate, etc.
Examples of phosphates include lithium phosphate, lithium dihydrogen phosphate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, and phosphoric acid.
Potassium hydrogen, potassium dihydrogen phosphate, magnesium phosphate, magnesium hydrogen phosphate, calcium phosphate,
Calcium hydrogen phosphate, calcium dihydrogen phosphate, strontium phosphate, strontium hydrogen phosphate, barium phosphate, barium hydrogen phosphate, barium dihydrogen phosphate, etc. As borates, lithium borate, Sodium borate, potassium borate, magnesium borate, calcium borate, barium borate, etc. 2. Acetate salts include lithium acetate, sodium acetate, potassium acetate, rubidium acetate, cesium acetate, magnesium acetate, calcium acetate, strontium acetate. , barium acetate, and the like. In addition, examples of 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-methylhexamethyleneimine, 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.

Preferred among these are organic amines, and more preferred are 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'.

These are tertiary amines such as N'-tetramethylhexamethylene diamine, pyridine, picoline, lutidine, collidine, and triethanolamine.

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 0,0001 mff or more times the amount 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 in too large a quantity, an effect proportional to the quantity cannot necessarily be obtained. In addition, in some cases, the presence of a stabilizer may have an adverse effect, so in reality, it is preferable to use the minimum amount necessary, taking into account the usage situation and stabilizing effect of aziridine-2-carboxylic acid amide. .

Therefore, in practice, when the stabilizer is (b) an organic amine, it is preferably 0.0001 times by weight to 100 times by weight relative to aziridine-2-carboxylic acid amide.
0.001 m-10 times the weight, more preferably 0.6 m
It is used in the range of 01 times to 1 times the polymerization. On the other hand, when the stabilizer is (a) alkali metal and alkaline earth metal hydroxides, carbonates, phosphates, Bo'fIi salts and vinegar R salts.

It is used in an amount of 0.0001 to 5001 to 5 times by weight, or 0.001 to 1 times by weight, more preferably 0.01 to 0.5 times by weight.

As for the method of adding the stabilizer, what is the method of adding the stabilizer in the present invention? Since aziridine-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, a stabilizer is added thereto. The stabilizer compound is preferably present in solution or suspension.

There is no particular restriction on the applicable temperature range of the stabilizer used in the present invention. The addition of a stabilizer is effective because aziridine-2-carboxylic acid amide undergoes deterioration even below room temperature, and the deterioration of aziridine-2-carboxylic acid increases at high temperatures of 50°C or higher, so the addition of a stabilizer is effective. becomes larger.

Experimental Examples Example 1 Aziridine-2-carboxylic acid amide 3. Og, and 1
60 ml of an aziridine-2-carboxylic acid amide synthesis reaction solution containing 5% by weight of ammonia was placed in a 200-ml flask. 0.3 g of N-methylpiperidine was added thereto, and from this solution, 30#I#1 was extracted using a rotary evaporator.
Ammonia and water were distilled off over a period of 7 hours on a water bath at 50°C under a reduced pressure of lI (+).The residue at this time was analyzed by liquid chromatography, and it was found that aziridine-2-
The residual rate of carboxylic acid amide was 9980%.

Comparative Example 1 Ammonia and water were distilled off in the same manner as in Example 1 except that N-methylpiperidine was not added. When the remaining solid was analyzed, the residual rate of aziridine-2-carboxylic acid amide was 89.8%.

Example 2 Example 1 was repeated substituting 0.3 g of trimethylamine for N-methylpiperidine. The residual rate of aziridine-2-carboxylic acid amide was 99.3%.

Example 3 Example 1 was repeated substituting 0.1 g of calcium hydroxide for N-methylpiperidine. The residual rate of aziridine-2-carboxylic acid amide was 91.7%.

Example 4 Aziridine-2-carboxylic acid amide synthesis reaction solution 501 containing 5.1 g of aziridine-2-carboxylic acid amide and 5% by weight of ammonia! Add 0.3y of 1-ethylamine to IIl, and boil to 30M using a rotary evaporator.
Ammonia and methanol were distilled off over 1 hour under reduced pressure of Hg on a 40°C water bath. The residual rate of aziridine-2 to carboxylic acid amide was 99.7%.

Comparative Example 2 Example 4 was repeated without adding triethanolamine. The residual rate of aziridine-2-carboxylic acid amide is 9
It was 1.3%.

Claims (1)

[Claims] 1. In a solution containing aziridine-2-carboxylic acid amide, (a) hydroxides, carbonates, phosphates, borates and acetates of alkali metals and alkaline earth metals, and (b) a method for purifying aziridine-2-carboxylic acid amide, which comprises adding a stabilizer consisting of a base selected from the group consisting of organic amines and subjecting it to a purification step. 2. The method according to claim 1, wherein the stabilizer is a tertiary amine.