NO774225L - PROCEDURE FOR THE PREPARATION OF 1-AZIRIDINE-CARBOXYLIC ACID RESIDUES - Google Patents

Description

Process for the production of 1-aziridine carboxylic acid ester derivatives

The present invention relates to new methods for the production of 1-aziridine carboxylic acid ester derivatives.

In Tetrahedron Letters 1964, 2^97, W. Lwowski et al. describe the 2-cyano-1-aziridine carboxylic acid ethyl ester as well as a method for its preparation, but no reference was made to a pharmacological effect. In the framework of the work on 2-cyan-l-aziridine-carboxamide, an immunostimulating therapeutic for bacterial and viral infections (see German patent application P 25 28 460.0), it has now been shown that 2-cyan-1- Aziridine carboxylic acid ethyl ester is a suitable starting material for the production of this therapeutic.

It has surprisingly been shown that the 2-cyano-1-aziridine carboxylic acid ethyl ester has a distinct immunostimulating effect. One is therefore faced with the task of developing this type of compound further, and of searching for improved methods for the production of the known and new compounds.

The subject of the present invention is now new methods for the production of the compounds with the general formula:

where

X is a nitrile, a carbamoyl or an alkoxycarbonyl group,

R is a straight-chain or branched, saturated or unsaturated alkyl group, which may optionally be substituted with halogen, alkoxy, amino, carbamoyloxy, cycloalkyl, hydroxy or imido or a heterocyclic group, or R may be cycloalkyl, aryl, aralkyl, aryloxyalkyl or arylthioalkyl, where the aryl group can optionally be substituted with halogen, alkyl, alkoxy, hydroxy, amino, nitro, cyano, acyl, carbaloxy, thioalkyl, alkylsulfonyl, phenyl or trifluoromethyl,

as well as the use of these compounds in the preparation of pharmaceuticals with an immunostimulating effect.

By alkyl is meant in all cases a straight-chain or branched chain with 1-5 carbon atoms. The methyl, ethyl, isobutyl, sec-butyl, t-butyl and n-pentyl groups are preferably used. The alkyl chains may optionally be substituted with halogen, such as fluorine,

chlorine and bromine, or an amino or hydroxy group. As further substituents, the carbamoyloxy group, preferably the 2-cyan-1-aziridine carbonyloxy group, an imido group, such as e.g. the phthalimido group, a heterocyclic group, especially 2-tetrahydro-furyl or The 2-tetrahydrothienyl group, the alkoxy or cycloalkyl groups use. Alkoxy under the substituents X and R in all cases means a group with 1-5 carbon atoms, preferably methoxy, ethoxy and isopropoxy. Cycloalkyl means groups with 3-10 carbon atoms, especially cyclopropyl, cyclopentyl, cyclohexyl as well as bridge-containing cycloalkyl groups such as e.g. boron-nyl group. Unsaturated alkyl groups are above all allyl-

and the crotyl group.

As an aryl group, aromatics with 6 -

10 carbon atoms, such as phenyl and naphthyl.

Aralkyl preferably denotes benzyl and phenethyl, while aryloxyalkyl preferably denotes 2-phenoxyethyl, and arylthioalkyl preferably denotes 2-phenylthioethyl.

As thioalkyl, methylthio is primarily used, and alkylsulfonyl is preferably methylsulfonyl. The acyl group is preferably the formyl and acetyl groups. Halogen means fluorine, chlorine and bromine. The aryl group can in all cases be substituted one or more times with the listed substituents.

The object of the invention is also all isomeric forms of a compound of the general formula I, which are obtained due to the asymmetric carbon atoms.

The subject matter of the invention is further the new compounds with the general formula:

where

X is a nitrile, carbamoyl or alkoxycarbonyl group,

R' is a straight-chain or branched, saturated or unsaturated alkyl group which may optionally be substituted with halogen, alkoxy,

amino, carbamoyloxy, cycloalkyl, hydroxy or imido or a heterocyclic group, or R' can be a cycloalkyl, aryl,

aralkyl, aryloxyalkyl or arylthioalkyl, whereby the aryl group may optionally be substituted with halogen, alkyl, alkoxy, hydroxy, amino, nitro, cyano, acyl, carbaloxy, thioalkyl, alkylsulfonyl, phenyl or trifluoromethyl,

in that when X is a nitrile group, R<*> cannot be ethyl .

As already mentioned, the connections with the general have

formula I surprisingly has a distinct immunostimulating effect. Moreover, when X is a nitrile group, they are valuable starting materials for the preparation of 2-cyano-1-aziridine carboxamide. For this, compounds of the general formula I where X is a nitrile group are reacted with ammonia to form 2-cyan-1-aziridine-carboxamide.

The compounds of the general formula I can be prepared by

methods known in and of themselves, preferably in that

a) an aziridine derivative of the general formula:

where

X is, as stated above, reacted with a halogen formic acid ester of the general formula:

where R is as indicated above, and Hal is chlorine or bromine, or b) a compound of the general formula:

where X, R and Hal are as indicated above, treated with halogen-releasing reagents, or c) a compound of the general formula:

where X and R are as above, by catalytic or photochemical

nitrogen removal is transferred to a compound of the general formula I, and that subsequently compounds of the general formula I are subsequently transferred to other compounds of the general formula

formula I.

The subsequent transfer of compounds with the general formula I to other compounds with the general formula I can optionally take place by transferring the substituent X. Here, e.g. compounds where X is alkoxycarbonyl, by reaction with ammonia are transferred to compounds where X is carbamoyl, as these can again be transferred with dehydrating agents to compounds where X is nitrile.

Compounds of the general formula I where X is alkoxycarbonyl and carbamoyl can therefore also be used as starting materials in the preparation of the compounds of the general formula I where x is nitrile, particularly 2-carbamoyl-1-aziridine carboxylic acid esters of the general formula in comes into consideration.

The transfer of the ester group to the amide group can best be carried out with gaseous ammonia in an organic solvent, preferably in methanol or ethanol. Equimolar amounts of ammonia are preferably used, and the reaction is allowed to proceed at from 0°C to +5°C. The desired amide is isolated from the reaction mixture, e.g. by column chromatography.

In the transfer of the carbamoyl group to the nitrile group, known dehydrating agents are used, in which above all the mixture of triphenylphosphine, carbon tetrachloride and triethylamine is used. Halogenated hydrocarbons are usually used as solvents, e.g. methylene chloride or chloroform. The desired nitrile is usually isolated from the reaction mixture by distillation.

On the other hand, e.g. also the substituents R and R'. are transferred to each other by general methods for transesterification, as generally a small addition of a basic compound, e.g. an alkali or alkaline earth metal hydroxide or an alkali alcoholate is required.

Moreover, the new compounds of the general formula I' can be prepared by reacting nitrenes of the general formula: where R' is as indicated above, with compounds of the general formula:

where X is as indicated above.

Nitrenes of the general formula VI, which can be prepared intermediately by photolysis of azidomauric acid esters or by u-elimination with the aid of bases such as triethylamine from N-p-nitro-benzenesulfonyloxyurethanes, react readily with the acrylic acid derivatives used to the desired aziridines of the general formula i< >>(eg Tetrahedron Letters, 1964, 2497; J. Am. chem. soc. 87, 3630 [1965]) .

In method a), the reaction partners can be reacted in inert solvents such as e.g. diethyl ether, methylene chloride, benzene or toluene in the presence of a base. Tertiary amines are preferably used as bases, such as e.g. triethylamine or triethanolamine. However, it is equally possible to work in a two-phase system such as water/diet here, as inorganic bases are then preferably used, especially sodium carbonate. Chloroformic acid esters are usually used as haloformic acid esters. These are partly described in the literature, but otherwise they can be produced by methods known per se by reacting the corresponding alcohol, or phenol, with phosgene in the presence of a base such as pyridine or N,N-dimethyla niline. The chloroformate esters are usually purified by distillation, but if

possibly also passed on as a raw product.

The dihaldene compounds used in method b) are

new and can be produced by reacting the corresponding compounds which are not halogenated at the nitrogen atom with halogenating agents, such as e.g. sodium hypohalite or t-butyl hypochlorite. For splitting off the two halogen atoms of the aziridine derivative with

in the general formula I, common dehalogenating agents can be used, preferably zinc or sodium.

The triazoline derivatives used in method c) are new

and can be produced by reacting diazoacetic acid derivatives such as e.g. diazoacetic acid ethyl ester or diazoacetonitrile with methylene urethanes. The nitrogen removal takes place either by illumination in a solvent such as e.g. diethyl ether or acetone, or catalytic. Precious metals or semi-precious metals, preferably copper powder, are used as catalysts.

For the production of pharmaceutical agents with an immunostimulating effect, the compounds of the general formula I are mixed in a manner known per se with suitable pharmaceutical carriers, and processed for example as tablets or dragees, or suspended or dissolved with the addition of corresponding excipients in water or oil, f .ex. olive oil, and filled in pop-up capsules. As the active substance is acid-labile, the preparation is supplied with a coating that is first soluble in the alkaline small intestinal environment or mixed with a corresponding carrier, such as e.g. a higher fatty acid or carboxy-methylcellulose. Solid carriers are e.g. starch, lactose, mannitol, methylcellulose, talc, highly dispersed silicic acids, higher-molecular fatty acids (such as stearic acid), gelatin, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats and solid high-molecular polymers (such as polyethylene glycols), for oral administration -stration suitable preparations can optionally have flavorings and sweeteners added.

As an injection medium, water is preferably used, which contains those for injection solutions. common additives such as stabilizers, solubilizers or weakly

alkaline buffers. Such additions are e.g. phosphate or carbonate buffers, ethanol, complexing agents (such as ethylenediaminetetraacetic acid and its non-toxic salts), high molecular weight polymers (such as liquid polyethylene oxide) for viscosity control.

Preferred in the present invention are, in addition to the compounds mentioned in the following examples, also the following: 2-cyano-1-aziridine-carboxylic acid-(1-chloroethyl ester) 2-cyano-1-aziridine-carboxylic acid-(1,2-dichloroethyl ester) 2-cyano-l-aziridine carboxylic acid-(1,2,2,2-tetrachloroethyl ester) 2-cyano-1-aziridine carboxylic acid-(2-methylphenyl ester) 2-cyano-1-aziridine carboxylic acid -(2-methoxyphenyl ester ) 2-cyano-l-aziridine carboxylic acid-(2-chlorophenyl ester) 2-cyano-l-aziridine carboxylic acid-(3-chlorophenyl ester) 2-cyano-l-aziridine carboxylic acid-(2,4 > 6- tribromophenyl ester) 2-cyano-l-aziridine carboxylic acid-(2-nitrophenyl ester) 2-cyano-l-aziridine carboxylic acid-(2-aminophenyl ester) 2-cyano-l-aziridine carboxylic acid-(3-aminophenyl ester) 2-cyano-1-aziridine carboxylic acid-(4-aminophenyl ester) 2-cyano-l-aziridine carboxylic acid-(2-hydroxyphenyl ester) 2-cyano-l-aziridine carboxylic acid-(4-hydroxyphenyl ester) 2-cyano-1-aziridine-carboxylic acid-(2-trifluoromethylphenyl ester) 2-cyano-1-aziridine-carboxylic acid-(3-trifluoromethylphenyl ester) 2-cyan -1-aziridine-ca rcarboxylic acid-(4-nitrobenzyl ester) 2-cyano-1-aziridine-carboxylic acid-(2-hydroxy ester) 2-cyano-1-a ziridine-ca rcarboxylic acid-cyclopropyl ester 2 -Cyano-1-aziridine-carboxylic acid-(2,2,2-trifluorinated ester) 2-Cyano-1-aziridine-carboxylic acid-(2-propoxyethyl ester) 2-Carbamoyl-1-aziridine-carboxylic acid-benzyl ester 2 -carbamoyl-1-aziridine-carboxylic acid-cyclohexyl ester is 2-carbamoyl-1-aziridine-carboxylic acid-(4-chlorophenyl ester) 1- ethoxycarbonyl-1-2-aziridine-carboxylic acid-isopropyl ester is 2- ethoxycarbonyl-1-aziridine-carboxylic acid -phenylest is 2-isopropoxycarbonyl-1-aziridine-carboxylic acid-(2,2,2-trichloroethyl- ester) 2-ethoxycarbonyl-1-aziridine carboxylic acid allyl ester

The following examples show some of the numerous process variants that can be used for the synthesis of process ef or - compounds.

Example 1

2- cyano-l-a ziridine- carboxylic acid- phenyl ester

To 6.8 g of 2-cyanaziridine in 70 ml of water, a solution of 12.6 g of chloroformic acid phenyl ester in 40 ml of diethyl ether and 40 ml of 2 N soda solution is simultaneously added at room temperature. The mixture is stirred for a further 2 hours at room temperature, the phases are separated, the ether layer is extracted twice with water, dried, and the organic phase is evaporated. The residue is recrystallized from diisopropyl ether. Yield: 10.39(67%). Temp. 60-62°C.

Analogously, one obtains by reacting 2-cyanaziridine with

1. Chloroformate methyl ester 2-cyano-1-aziridine carboxylic acid methyl ester

KP0.02: 70 - 72°C

2. Chloroformic acid-(2,2,2-trichloroethyl ester) 2-cyano-l-aziridine-carboxylic acid-(2,2,2-trichloroethyl ester)

KpQ 1 : 138 - 139°C Mp.: 86 - 88°C (diisopropyl ether)

3- Chloroformic acid allyl ester

2- cyan- l - azi r id in- ca rboxy 1 acid- a Hylest is

KpQ 2 : 102 - 105°C

4> Chlormaursy re-t-butyl ester (used as ethereal solution)

2- cyano- 1-a ziridine-ca rboxylic acid-t-butyl ester is

k<p>0.oi: 57 * 59°c

5. Chloroformate-n-pentyl ester<r>(Kp100 : 98 - 100°C) 2-cyano-l-aziridine-carboxylic acid-n-pentyl ester is

k<p>0.0i: 93°c

6. Chloroformic acid cyclohexyl ester (Kp^: 47°C) 2-cyano-l-aziride in-ca rboxylic acid cyclohexyl ester is

k<p>0.0i: 97°c

7« Chloroformic acid benzyl ester

2- cyano- 1- aziridine- carboxylic acid benzyl ester

bp0,oi : 145"150°c

8. Chloroformic acid phenethyl ester (KP]_g : 120°C) 2-cyano-l-aziridine-carboxylic acid phenethyl ester is

KP0,oi: 130°c

Example 2

1,2-aziridine-dic carboxylic acid diethyl ester is

To 2 g of 2-aziridine carboxylic acid ethyl ester and 1,79 triethylamine 1 20 ml of benzene is added dropwise at 0°C a solution of 1.9 g of chloroformic acid ethyl ester in 10 ml of benzene, which is then stirred for 2 hours at room temperature, extracted three times with water, the benzene phase is dried and evaporated. The residue is then distilled.

•*Yield: 2.0 g (62%). KpQ 2 : 94°C

Example 3

2-carbamoyl-1-aziridine carboxylic acid phenyl ester

To 2.6 g of 2-aziridine carboxamide in 20 ml of water is simultaneously added dropwise at 0°C a solution of 4.79 chloroformic acid phenyl ester in 20 ml of diethyl ether and 30 ml of 2 N soda solution. Stirring is continued for 10 minutes under ice cooling, the precipitate is suctioned off and washed well with ether.

Yield: 4.4 g (71%). M.p.: 140 - 142°C from toluene.

Example 4

2 - cyan- 1 - azi ridine- carboxylsy r e- a Hy les ter

To 2 g of 2-cyanaziridine in 20 ml of benzene and 39triethylamine, 3.2 g of chloroformic acid allyl ester in 20 ml of benzene are added at 0°C. Stirring is continued for 2 hours at room temperature, the benzene solution is extracted twice with water, dried, and the organic phase is evaporated. The residue is then distilled.

Yield: 2.9 g (64.5%). KpQ 2 : 102 - 105°C

Analogously, one obtains by reacting 2-cyanaziridine with chloroformic acid ethyl ester

2- cyano-l-aziridin-ca rboxylic acid-ethyl ester

Kpo'^o7T~o -75°c

Example 5

2- carbamoyl-1-aziridine-carboxylic acid ethyl ester is

2.6 g of 2-aziridine carboxamide in 20 ml of water is added drop by drop

under ice-cooling at the same time a solution of 3.25 g of chloroformate

ethyl ester in 20 ml of diethyl ether and 15 ml of 2 N soda solution. The reaction mixture is further stirred for 1 hour while cooling,

the layers are separated, the aqueous phase is evaporated, and the residue is boiled off with ethanol. The ethanol solution is filtered, evaporated, and resi-

duet omcross is allized from toluene.

Yield: 2.6 g (56%). Melting point: 125 - 128°C.

Analogously, by reacting 2-aziridine-

carboxamide with chloroformic acid methyl ester

2- carbamoyl- 1- aziridine- carboxylic acid- methyl ester

Mp.: 117 - 120°C (from toluene). 1

Example 6

Preparation of .2-cyano-1-aziridine-carboxamide from 2-cyano-1-aziridine-carboxylic acid phenyl ester is

1.9 g of 2-cyano-1-aziridine carboxylic acid phenyl ester is dissolved in

30 ml of diethyl ether and add 20 ml of liquid ammonia drop by drop. The mixture is stirred for 2 hours at the temperature of boiling ammonia, the solution is allowed to reach room temperature overnight, and the precipitated 2-cyano-1-aziridine carboxamide is filtered off with suction.

Yield: 0.85 g (77%). Melting point: 74 - 76°C.

Example 7

2 - cyan- 1 - azi ridine- carboxy lsyre- met.hy lest er

To a solution of 27.5 Q of triphenylphosphine, 10.1 g of triethylamine and 15.4 g of carbon tetrachloride in 300 ml of methylene chloride, 14.4 g of 2-carbamoyl-1-aziridine carboxylic acid methyl ester is added, and the mixture is refluxed for 4 hours . The reaction mixture is filtered, the solution is extracted twice with water, the organic phase is dried and evaporated. The residue is distilled.

Yield: 3.4 g (27%). KpQ Q2 : 70 - 72°C.

Example 8

2- carbamoyl-l-aziridine-carboxylic acid ethyl ester

To 4.67 g (0.025 mol) of 1,2-aziridine dicarboxylic acid diethy ester in 30 ml of ethanol is added the equimolar amount of gaseous ammonia dissolved in ethanol, and the solution is left overnight in a refrigerator. It is evaporated, and the desired 2-carbamoyl-1-aziridine-carboxylic acid ethyl ester is isolated by column chromatography (200 g silica gel, eluent acetone/toluene volume ratio 1:1).

Yield: 1.4 g (32%). Melting point: 125 - 128°C.

Example 9

Preparation of 2-cyan-l-aziridine-carboxamide from 2-cyan-l-aziridine-ca rboxylic acid- et hy le st er

4 g of 2-cyano-1-aziridine carboxylic acid ethyl ester are added

a solution of 0.79 ammonia gas in 80 ml of water. The mixture is stirred at room temperature for 4 hours, extracted three times with ethyl ether, and the aqueous phase is then freeze-dried. The residue is recrystallized from ethanol with the addition of diethyl ether.

Yield: 1.059(29%). Melting point: 74 - 76°C.

Example 10

2-Cyano-1-aziridin- carboxylic acid ethyl ester

To 2.11 g of 2-(N-carbethoxy-N-chloro-amino)-3-chloropropionitrile (oily compound, prepared by reacting 2-amino-3-chloropropionitrile hydrochloride (m.p. 153 - 155°C) with chloroformic acid -ethyl ester in the presence of sodium carbonate with subsequent reaction with t-butyl hypochlorite) in 25 ml of ethanol, 0.339 activated zinc dust and some zinc chloride are added, the mixture is stirred for 12 hours at room temperature, filtered off, the filtrate is evaporated, and the residue is distilled.

Yield: 0.11g (8%). KpQ 01 : 78 - 80°C.

Example 11

As described in example 1, one obtains by reacting 2-cyano-aziridine with: 1. Chloroformic acid isobutyl ester 2-cyano-l-aziridine carboxylic acid isobutyl ester is KpQ 1 : 108 - 110°C 2. Chloroformic acid cyclopropyl- methyl ester (Kp12: 45 - 46°C) 2- cyano-l-aziridine-carboxylic acid- cyclopropyl- methyl ester is KpQ)1: 107 - 109°C 3. Chloroformate-(but-2-enyl ester) (Kp O , J- 25 - 28°C) 2-cyano-1-aziridine-carboxylic acid-(but-2-enyl ester)

oily product

4. Chloroformic acid cyclopentyl ester (Kp^: 60 -.61°C) 2-cyano-l-aziridine-carboxylic acid cyclopentyl ester is

oily product

5. Chloroformic acid-bornyl ester (Kp2: 108 - H0°C) 2-cyano-l-aziridine-carboxylic acid-bornyl ester

Kp0)1: 153°C

6. Chloroformic acid-(2-fluoroethyl ester) (Kp : 110 - 113°C) 2-cyano-l-aziridine-carboxylic acid-(2-fluoroethyl ester) Kp0)1: 120°C 7. Chloroformic acid-(2-chloroethyl ester) ( Kp^Q: 83 - 86°C) 2-cyano-1-aziridine-carboxylic acid-(2-chloroethyl ester) oily product 8. Chloroformic acid-(2-bromometh<y>lester) 2-cyano-1-a ziridine - carboxylic acid-(2-bromomethyl ester) oily product 9 . Chloroformic acid-(2-methoxyethyl ester) 2-cyano-1-aziridine-carboxylic acid-(2-methoxyethyl ester) KpQ x : 119-120°C 10. Chloroformic acid-tetrahydrofurfuryl ester (KpQ 2 : 68°C) 2-cyano-1-aziridine - carboxylic acid tetrahydrofurfur uryl ester oily product 11. A hylene glycol-1,2-bis-chloroformic acid ester (KPg^: H0°C) 1, 2-[ bis-(2- cyanaziridin-1-ca rbonyloxy)]-etha n oily product 12. Chloroformic acid-(2-phenoxyethyl ester) (KpQ1: 97 - 99°C) 2-cyano-l-aziridine-carboxylic acid-(2-phenoxyethyl ester) oily product 13. Chloroformic acid-(2-phenyl-thioethyl ester) 2-cyano-1-aziridine-carboxylic acid-(2-phenyl-1-thioethyl ester) oily product

14- Chloroformate-(l-naphthyl ester) (KpQ ^ : 86 - 90°C)

2-cyano-l-aziridine-carboxylic acid-(1-naphthyl ester) oily product

15-Chloroformic acid-(4-methylphenyl ester) (Kp30<:><10>5 -<106>°<C>)

2- cyano- 1- aziridine- carboxylic acid-(4- methylphenyl ester)

Temp. 88 - 90°C (isopropanol)

16. Chloroformic acid-(2,4-dimethylphenylester) (Kpl2: 100 - 101°C) 2-cyano-1-aziridine-carboxylic acid-(2,4-dimethylphenylester)

Temp. 90 - 91°C (ethanol) •

17. Chloroformic acid-(4-sec-butyl-phenylester) ■ (Kp12 : 122 - 123°C) 2-cyano-1-aziridine-carboxylic acid-(4-sec-butyl-phenylester)

Temp. 74 - 75°C (Ligroin)

18• Chloroformic acid-(4-biphenyl ester)

2- cyano- 1- aziridine- carboxylic acid-( 4- biphenyl ester)

Temp. 107 - 109°C

19. Chloroformic acid-(4-methoxyphenyl ester) (Kp12: 115 - H7°C) 2-cyano-1-aziridine-carboxylic acid-(4-methoxyphenyl ester)

Temp. 54 - 57°C (diisopropyl ether)

20. Chloroformic acid (4-chloro-2-methoxyphenyl ester) (Kp2Q : 138 l40°C) 2-cyano-1-aziridine-carboxylic acid-(4-chloro-2-methoxyphenyl ester) M.p. 114 - H5°C (isopropanol) 21. Chloroformic acid-(2-fluorophenyl ester) (Kp 2 : 68 - 70°C) 2-cyano-l-aziridine-carboxylic acid-(2-fluorophenyl ester)

Temp. 55 - 56°C (isopropanol/water)

22.Chloroformic acid-(4-trifluoromethylphenylester) (Kp12: 82 - 84°C) 2-cyano-l-aziridine-carboxylic acid-(4-trifluoromethylphenylester) M.p. 75 - 77°C (diisopropyl ether) 23. Chloroformic acid-(4-chlorophenyl ester) (Kp12: 97 - 99°C) 2-cyan-1-aziridin-carboxylic acid-(4-chlorophenyl ester)

Temp. 79 - 82°C (diisopropyl ether)

24. Chloroformic acid-(2,4-dichlorophenyl ester) (Kpg : 112 - H7°C) 2-cyano-1-aziridine-carboxylic acid-(2,4- dichlorophenyl ester)

Temp. 82 - 84°C

25. Chloroformic acid-(2,4,5-trichlorophenyl ester) (Mp.: 58 - 6o°C) 2-cyano-l-aziridine-carboxylic acid-(2,4;5-trichlorophenyl ester) M.p. 100 - 103°C (diisopropyl ether) 26. Chloroformic acid-(4-bromophenyl ester) (Kp12: 111 - H3°C) 2-cyano-1-aziridine-carboxylic acid-(4-bromophenyl ester)

Temp. 96 - 100°C (diisopropyl ether)

27. Chloroformic acid-(3-nitrophenyl ester) (KpQ ^ •: 120 - 122°C) 2-cyano-l-aziridine-carboxylic acid-(3-nitrophenyl ester)

Temp. 98 - 100°C (isopropanol)

28- Chloroformic acid-(4-nitrophenyl ester)

2-cyano-l-aziridine-carboxylic acid-(4-nitrophenyl ester)

Temp. 107 -.111°C (diisopropyl ether)

29. Chloroformic acid-(4-methylthiophenyl ester) (KpQ 2 : 108°C) 2-cyano-l-aziridine-carboxylic acid-(4-methylthiophenyl ester) M.p. 73 - 75°C (isopropanol) 30. Chloroformic acid-(2-methylsulfonylphenyl ester) (Mp. 100 - 103°C) 2-cyano-l-aziride in- carboxylic acid-(2-methylsulfonylphenyl ester) Mp. 145 - 150°C (isopropanol) 31. Chloroformic acid-(3-formylphenyl ester) (KpQ ^ : 125°C) 2-cyano-l-aziridine-carboxylic acid-(3-formylphenylester) oily product 32. Chloroformic acid-(4- acetyl.phenyl ester) (Kp,- : 121 - 123°C)

2 ->cy an- l-aziridine-carboxylic acid-(4- acetylphenyl ester)

Temp. 104 - 107°C

33-Chloroformic acid-(4-carbomethoxyphenyl ester) (M.P.: 47 - 50°C)

2-cyano-1-aziridine-carboxylic acid-(4-carbomethoxyphenyl ester) M.p. 86 - 87°C (isopropanol)

34. Chloroformic acid-(4-cyanophenyl ester) (Kp O j 1: 92-94°C) 2-cyano-1-aziridine-carboxylic acid-(4-cyanophenyl ester)

Temp. 95 -. 99°C (acetic acid/naphtha)

35. Chloroformic acid-(2-phthalimidoethyl ester) (Mp. 75 - 77°C) 2-cyano-l-aziridine-carboxylic acid-(2- phthalimidoethyl ester) M.p. 160 - 163°c (ethanol)

Compounds obtained as "oily product" were characterized by NMR and mass spectroscopy.

Claims (5)

1. Procedure for the preparation of 1-aziridine carboxylic acid ester derivatives with the general formula: where X is a nitrile, carbamoyl or alkoxycarbonyl group, Re straight-chain or branched, saturated or unsaturated alkyl which is optionally substituted with halogen, alkoxy, amino, carbamoyloxy, cycloalkyl, hydroxy or imido or a heterocyclic group, or R is cycloalkyl, aryl, aralkyl, aryloxyalkyl or arylthioalkyl where the aryl group can in each case be substituted with halogen, alkyl, alkoxy, hydroxy, amino, nitro, cyano, acyl, carbaloxy, thioalkyl, alkylsulfonyl, phenyl or trifluoromethyl, characterized in that in a manner known per se) an aziridine derivative with the general formula: where x is as indicated above, is reacted with a haloformic acid ester of the general formula: where R is as indicated above, and Hal is chlorine or bromine, or b) a compound with the general formula: where X, R and Hal are as indicated above, treated with halogen- cleaving reagents, orc) a compound of the general formula: where X and R are as indicated above, by catalytic or photochemical nitrogen removal is transferred to a compound of the general formula I, and that then possibly compounds with the general formula I are transferred to other compounds with the general formula I. 2. 1-aziridine carboxylic acid ester derivative is characterized by having the general formula: where X is a nitrile, carbamoyl or alkoxycarbonyl group, R * is straight-chain or branched, saturated or unsaturated alkyl which may optionally be substituted with halogen, alkoxy, amino, carbamoyloxy, cycloalkyl, hydroxy or imido or a heterocyclic group, or R' is cycloalkyl, aryl, aralkyl, aryloxyalkyl or arylthioalkyl where the aryl group in each case may optionally be substituted with halogen, alkyl, alkoxy, hydroxy, amino, nitro, cyano, acyl, carbaloxy, thioalkyl, alkylsulfonyl, phenyl or trifluoromethyl, with the proviso that when x is a nitrile group, R' cannot be ethyl. 3. Process for the production of 1-aziridine carboxylic acid ester derivatives according to claim 2, characterized in that nitrenes with the general formula: where R' is as indicated above, is reacted with a compound of the general formula: where X is as indicated above. 4» Use of compounds of the general formula I, where X is a nitrile group, as starting material in the preparation of 2-cyano-1-aziridine carboxamide. 5. Use of compounds of the general formula I, where X is carbamoyl or alkoxycarbonyl, as starting material in the preparation of compounds of the general formula I, where X is a nitrile group.