CS196523B1 - Process for preparing aziridines - Google Patents

Abstract

Cpds. of formula (I): (wher R1,R2,R3 and R4 = H, alkyl, cycloalkyl or aryl; R1-C-R2, R3-C-R4, R1-C-C-R3 or R2-C-C-R4 may be part of a heterocyclic ring; R5 = H, alkyl, cycloalkyl or Cl); are prepd. by reacting a cpd. (II): with a cpd. (III): R5-NH-X in an org. solvent such as toluene, benzene, ethers etc. at pref. room temp. (I) are used as inters. in the prepn. of amino alcohols, diamines and heterocyclic cpds. which are used as additives in plastics prepn., or in the synthesis of pharmaceuticals and plant-protection agents. The process is simple, does not form by-prods. and is not dangerous in any way.

Description

The invention relates to a process for the production of aziridines from olefins.

It is known that aziridines can be produced by ring closure of Λ -halememines or from esters of sulfuric acid with β-aminoalcohols. If olefins are used as starting materials, these compounds must first be converted to β-haloamines or β-aminoalcohols. Thus, they are produced not. ethyleneimine as the base unit, and then ethylene is chlorinated to dichloroethylene and then reacted with ammonia. The known processes for the production of carbon-substituted aziridines from olefins are complicated. They consist, for example, in reacting the olefin with nitrosyl chloride, iodide, Ν, Ν-dichlorourethane or iodine isocyanate to form a ^-haloalkyl nitrogenous compound whose nitrogen-containing group is converted to the amino group necessary for ring closure by reduction or saponification . The compound thus obtained is then cyclized to aziridine.

However, it is also known that these aziridines can be obtained so that the olefin epoxide is opened, the epoxy ring is opened with ammonia and the resulting amino alcohol is converted to aziridine via its sulfuric acid ester.

It is well known that aziridines substituted on a nitrogen atom can be produced first and these aziridine derivatives are altered by cleavage of the substituent on the nitrogen atom to aziridines unsubstituted on the atom. This can be done, for example, by simultaneous coupling of halogen and nitrile groups to olefins. of the compounds to the .beta.-haloalkylacylamines by cyclizing the acylamines with N-acylazAridines with bases. The acyl group can be cleaved from these compounds in a known manner to give unsubstituted aziridines.

It is further known that azides can be reacted with olefins at elevated temperature or by photochemical processes to form aziridines by cleavage of the nitrogen atom to form triazolines or nitrenes as intermediates.

Finally, a number of special reactions are described in which olefins are converted to aziridines by nitrenes formed in situ using the most complicated reagents, for example diacylhydrazine and lead tetraacetate or, in particular, C1, β-unsaturated amines through the oxidation of the bicyclic azlridines.

It has also been proposed to obtain unsubstituted aziridines by reaction between olefins and oxaziridines not substituted on a nitrogen atom.

All of the above processes are not suitable for large-scale production of azlridines because they require either several preparative steps, costly in time, or difficult to access reagents, or process 8 using azides, which is dangerous.

It is an object of the present invention to overcome the disadvantages of the above known processes.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a process for the preparation of azlridines from olefins which is simple, does not entail any danger, and the conversion of olefins to a variety of compounds is possible, with the conversion of olefins directly to aziridines.

It is therefore an object of the present invention to provide a process for the preparation of the azlridines of formula (I)

(AND),

About 5 * Ί Λ where R 'R, R ^J and R are hydrogen atoms, alkyl groups having 1 to 10 carbon atoms, phenyl or alkoxyphenyl having 1 to 3 carbon atoms in the alkoxy group, wherein R! - C - C - R 1 or R 2 - C - C - R 3 optionally forms part of a cycloaliphatic ring of 5 to 7 carbon atoms and R 6 represents a hydrogen atom, an alkyl group of 1 to 4 carbon atoms or a cycloalkyl group of 5 to 7 of the olefins of formula II

(II), wherein r 1, R 3, r 3 and R 4 are as defined above, which is carried out by reacting olefins of formula II with an N-halogenated compound of formula III or a compound of formula IV

R ⁵ -NH-X (III)

R ⁵ - NH ₂ (IV), wherein the above meaning a

X represents a chlorine or bromine atom, in an organic solvent at a temperature

C to 150 ° C, preferably at room temperature and the aziridine ее thus formed is isolated from the refraction mixture in a known manner.

The N-halogenated compounds of formula (III) used to carry out the process of the invention are readily available. E.g. chloramine can be produced by gas-phase chlorination of ammonia or by reaction of ammonia with a hypochlorite solution. Dichloramine can be obtained by disproportionation of chloramine solutions in the presence of weak acids. N-Alkylchloramines or N-chlorocycloalkylamines can be obtained particularly easily by treating hypochlorite solutions on the corresponding primary amines. N-halogenated amine solutions can be used without any danger.

A great advantage of the process according to the invention is that it takes place in a single stage. The solution of the olefin and the halogenated compound of formula III is reacted in an organic solvent such as toluene, benzene, chloroform, ether, dioxane or tetrahydrofuran at a temperature of 0 to 150 ° C, preferably at room temperature. The degree of conversion may depend on a decrease in the oxidation capacity of the solution. The reaction mixture is worked up in a known manner by distillation or extraction with aqueous acid solutions.

In contrast to the aforementioned known processes for the production of azirins, the process according to the invention proceeds without the formation of undesired by-products. When the amine corresponding to the N-halogenated compound is formed, it can be returned to the reaction mixture. Also, unreacted olefin, which is often used in excess, can be recycled. In the case of liquid olefin, the olefin may be used directly as the reaction medium.

The aziridines produced by the process of the invention are valuable intermediates for the production of amino alcohols, diamines and heterocyclic compounds which are used as additives in the manufacture of plastics or in the synthesis of pharmaceuticals or plant protection agents. Example 1

A solution of 1.2 g (24 mmol) of chloramine in 200 ml of benzol, produced by chlorination of ammonia in the gas phase, is mixed with 26 g (223 mmol) of methylstyrene and heated in an autoclave at 100 DEG C. for 75 minutes. The presence of chloramine can no longer be detected.

The light yellow solution is extracted with 30 ml of ice-cold 2 N sulfuric acid and the sulfuric acid phase is immediately added to 15 ml of 30% sodium hydroxide solution.

198 523

After 'extraction with ether, the ether solution was anhydrified over sodium sulfate and distilling off the ether gave 1.3 ^{g of 2-phenyl-2-:} methylene and ^{L i} r · nu ^{idi t} EPLO about ^thee boiling £ 94 and 95 ° C ^{at pressure} at 1866 psi, indicating yield 40% of theory '· amount _of

Example 2

A solution of 1.5 g (30 mmol) of chloramine in 50 ml of dioxane is treated with 18 g (150 mmol)

OC-methylstyrene and the mixture was allowed to stand at room temperature for 14 days. The chloramine content is then reduced to 9%. The solution obtained is extracted with 30 ml of ice-cold 2 N sulfuric acid by adding a few drops of saturated potassium iodide solution and the sulfuric acid phase is added to 15 ml of a 30% solution. sodium hydroxide. After extraction with ether, the ethereal phase anhydrified over sodium 'sulfate and the ether was distilled off to give 0.8 g of 2-methyl-2-nylaziridinu ^t e ^p a lot ^of boiling 9, ⁴ and ⁹⁵ ° ^C and ^{at pressure} in ^{the to 1.866} Pa ^s represents C ^oz howl ^{Ezek 20% of} the theoretical value.

Example 3

An ethereal solution of 5.0 g (5 mmol) of N-chloro-n-propylamine was prepared from n-propylamine and sodium hypochlorite and treated with 170 ml of dioxane and the ether was evaporated in vacuo. Was added 26 ^g (223 mmol) OC / ^s lat methylbenzyl ^s role and the mixture was heated ^and at 34 and suture ^^ ^{2 h} of ^di n to 100 ° C. N-Chloro-n-propylamine can then no longer be detected. The solution thus obtained is extracted with 50 ml of ice-cold 2 N sulfuric acid solution and this phase is added to 25 ml of 30% sodium hydroxide solution. After extraction with ether, the solution .etherický anhydrified over sodium sulfate and the ether was distilled off to obtain 4.1 g of l-propyl-phenyl -methylaziridine ^ o 'b.p. ⁸⁰ 5 ^{and 8} ° C, pH 13.33 to ^ t ^p and ^{meaning and} you ^{Photogene, white} e ^{to 43%} of the theor ^t lck ^{Ehe LeVeLs} 8tví.

Example 4

4.0 g solution prepared from cyclohexylamine and sodium hypochlorite. (30 mmol) of N-chlorocyclohexylamine in 80. ml of toluene was refluxed with 17.5 g (150 mmol) of N-methylstyrol for 7 hours. N-Chlorocyclohexylamine is then no longer detectable. Ee cyklohexylaminhydrochlorid precipitated was filtered off and the filtrate was distilled, yielding 3.0 g ^{l-cyclohex yl-2-methyl-2-phen yl} laz ⁱ r ⁱ a pyrrolidine te ^{pl of} rev. boiling point ^120-1 ° ^{C 2} 3 and ^BC 1 ⁰⁶ 6 Pa _R representing a yield of 46% of theory.

Example 5

A solution of 8.7 g (70 mmol) of N-bromoethylamine in 150 ml of ether was mixed with bromine and ethylamine and treated with 41.3 g (350 mmol). N, N-methylstyrene and the mixture was allowed to stand at room temperature for 6 hours. The bromethylamine-free solution is distilled first at atmospheric pressure and then under vacuum from an oil pump. This way e ZIS ^{ka 4.06} g of L-Etayo ^ ^ -metayl- fBnylaziriůin b.p. 50-5 ² ° C at a pressure of 40 Pa, which corresponds to a yield of 36 '% of theory.

Example 6 '

Solution. 7.2 g (58 mmol) of N-bromoethylamine in 140 ml of ether were allowed to stand at room temperature with 32 g (292 mmol) of styrene for 5 hours. This solution then contains practically no N-bromoethylamine. The solution is mixed with 30 ml of a 2 N sulfuric acid solution and the extract is mixed with 10 ml of a 30% sodium hydroxide solution. After extraction with ether, ethereal

198,523 phases anhydrified over sodium sulfate, 'and the ether' · distilled off to obtain 3757 g of L-ethyl-2 ^- phen ^yl laziridinu · b.p. 47 ° ^{C at pressure} and ^to at 40 Pa, which by ^p s ^d d ^and 41. % 'of the theoretical amount.

Example 7.

A solution of 9.3 g (70 µl) of N-chlorocyclohexylamine in 110 ml of toluene prepared from cyclohexylamine and sodium hypochlorite was refluxed with 58.8 g (350 mmol) of dodecene for 1/4 hour. Then, N-chlorocyclohexylamine can no longer be detected in solution. The solution obtained is extracted with 40 ml of a 2 N sulfuric acid solution and this phase is mixed with 20 ml of a 30% sodium hydroxide solution. After extraction and distilling off the ether gave 1.4 g LC lohex ^{yk y 2} -n-l- ^yl DEC / ^l / ⁱ Azir pyrrolidine, o ^{t h} e ^p lo ^thee point ^{of 100} DEG -110 DEG C. at a pressure of 4 Pa ⁰ what said ^{Z d} 7% yield of theory.

Example 8. 200 ml of n-butylamine and sodium hypochlorite prepared solution of 10.2 g '(96 mmol)

N-chloro-n-but ^ ^y la iinu alcohol was heated at reflux e 56 g (310 mmol) of trans-St-Ben 7 hours. Then, N-chloro-n-butylamine can no longer be detected in solution. The solution obtained is extracted with 40 ml of a 2 N sulfuric acid solution and this phase is mixed with 15 ml of a 30% sodium hydroxide solution. After extraction with ether, stripped extract over anhydrous sodium sulphate and distilling off the ether gave 2.85 g ln-butyl-2,3-diphenyl-aziridine b.p. 125-130 ° ^C at ^66.6 t ^l battery · Pa, a ^CO O6 ^P ov ^IDA. OCT ^thee above ^12% of th ^ Kehoe amount.

. Example 9 A solution of 1.0 g (12.3 mmol) of dichloramine in 156 ml of ether, prepared by disproportioning 1.3 g (25 mmol) of chloramine with a solution of sodium phosphate in water, was allowed to stand at room temperature with 17.5 g. (150 mmol) of OC-methylstyrol for 48 hours · Then the mixture is extracted with 20 ml of 2 N sulfuric acid solution with the addition of a few drops of saturated potassium iodide solution and then mixed with 5 ml of 30% sodium hydroxide solution. mixture of ether · this phase anhydrified with sodium sulfate and distilled to .ether U is ^L, 'whereby ^f is from ⁱ to ^{ka 0,} 9 ^{g of 2-:} methylene ^LF en ^yl Azir ⁱ d ⁱ nu ^{te p} lot ^of boiling point 94-95 ° ^C at a pressure of 1866 kPa, a howl from ^p ovide ^EZK 55% of the theoretical amount ^ yours.

Example 10

A solution of 1.1 g (12.5 mmol) of dichloramine in 100 ml of ether was allowed to stand for 3 days at room temperature with 16.7 g (125 mmol) of para-methylstyrol. The solution is extracted with 20 ml of a 2 N sulfuric acid solution with the addition of a few drops of saturated potassium iodide solution. This phase is then mixed with 5 ml of 30% sodium hydroxide solution. After extraction with ether, the extracts anhydrified over sodium sulfate, 'and the ether is distilled off to give 1,13'g 2- ^{(p-methoxy) phenoxy-yl} laziri ^di · nu te ^ OTE boiling 6 ² ° ^C at ^t l'battery 4 ^{0 Pa,} which from ^p ovide a yield of 60% of theory.

Example 11. A solution of 6.0 g (65 mmol) of N-chloro-n-propylamine in 180 ml of tetrahydrofuran prepared from n-propylamine and sodium hypochlorite was heated with 70 g (650 moles) of styrene for so long.

The reaction solution was refluxed until the reaction solution no longer contained N-chloro-n-propylamine. The solution is extracted with 50 ml of ice-cold 2 N sulfuric acid and this phase is mixed with 15 ml of 30% sodium hydroxide solution and extracted with ether. The ether extract was dehydrated with sodium sulfate and the ether was distilled off to give 2.65 g of 1-propyl-2-phenylaziridine, b.p. 50-53 ° C at 1 mmHg. Yield: 27% of theory.

Example 12

A solution of 5.1 g (i.e., 48 mmol) of N-chloro-n-butylamine in 100 ml of chloroform is prepared from n-butylamine and sodium hypochlorite until refluxing with 21 g (200 mmol) of styrene is no longer possible. show no N-chloro-n-butylamine. The solution is then extracted with 40 ml of 2 N sulfuric acid and this phase is then mixed with 15 ml of 30% sodium hydroxide. After extraction with ether, the extract was dehydrated with sodium sulfate and the ether was distilled off

to give 1.5 g of 1-n-butyl-2-phenylaziridine having a boiling point of 62-65 ° at a pressure of 66.6

Pa, corresponding to a yield of 18% of the theoretical amount.

Example 13

A solution of 4.7 g (50 mmol) of N-chloro-n-propylamine in 80 ml of toluene prepared from n-propylamine and sodium hypochlorite was heated at reflux for 18 hours with 18.8 g (200 mmol) of norbornene. N-chloro-n-propylamine can no longer be detected in the solution. The solution obtained is extracted with 40 ml of ice-cold 2 N sulfuric acid and this phase is mixed with 15 ml of 30% sodium hydroxide and then extracted with ether. The ether phase is dehydrated with sodium sulfate and the ether is distilled off to give 1.43 g of 3-propyl-3-azatricyclo [3.2.1.0 < 2,10 &^gt; ^oxo ] octane, b.p. corresponding to a yield of 20% of the theoretical amount.

Example 14

A solution of 1.5 g (29 mmol) of chloramine in 200 ml of benzol, produced by gas-phase chlorination of ammonia, was heated in a calorimetric bomb with 24.6 g (300 mmol) of cyclohexene at 90-100 ° C for 90 minutes. The solution is extracted with 40 ml of ice-cold 2 N sulfuric acid with the addition of a few drops of saturated potassium iodide solution and then immediately mixed with 15 ml of 30% sodium hydroxide. After extraction with ether, the extract is dehydrated with sodium sulphate and the ether is distilled off to give 1.0 g of 2,3-tetramethylenaziridine, bp 56-57 ° C at 2.0 kPa, corresponding to a yield of 35% of theory.

Example 15

A solution of 1.2 g (14.5 mmol) of dichloramine in 130 ml of ether was allowed to stand at 17.5 g (145 mmol) of n-octene (1) for 24 hours at room temperature. After extraction with 30 ml of ice-cold 2 N sulfuric acid with a few drops of potassium iodide solution and addition of 15 ml of 30% sodium hydroxide solution, the solution is extracted several times with ether, the extracts are dehydrated with sodium sulfate and distilled off to obtain 0.2 g -n-hexylaziridine in 10% yield.

Example 16

A solution of 6.2 g (50 mmol) of N-bromoethylamine in 100 ml of benzol was left to stand

14.9 g (100 mmol) of m-nitrostyrol at room temperature for 24 hours. Solution that no longer neo7

198 523 contains no N-bromoethylamine, extracted with 30 ml of 2 N sulfuric acid, then free base is liberated from the extract by treatment with 10 ml of 30% sodium hydroxide. This one. substance is mixed with ether, dried over sodium sulphate and after distilling off the ether · in this way in a yield of 30% of theory ^and SK ^and 2.9 ^{g of} ethyl ^ ^^ ^ m-nttrofeny ziridinu on te ^p · ture point of 84 ° C ^{at a} pressure of 6.66 Pa.

r

Example 17

A mixture of 106 g (900 mmol) of d-methylatyrol and 50 ml of carbon tetrachloride is heated to boiling, and a solution of 360 mmol of N, Nd ± bromomethylatoin obtained from methylamine hydrochloride and 2 moles of sodium hypobromite is added dropwise over 15 minutes. temperature -5 to ⁰ ° C. Solution ^of E in sequence ^to reaWního ^t e ^p u la POMA ^l boiled and oxi ^d and ^{N NU} setopnost solution decreases. The solution is cooled and extracted with 200 ml of cold 2 N sulfuric acid. From sour. solution is freed of 1,2-dimethyl-2-phenylaziridine adding 50 ml of concentrated sodium hydroxide solution, this was extracted with ether and after drying and evaporation of the solvent in this manner in 67% of mined "it množetv of theoretical ^ ^í á ZIS ^to 35.7 ^{g 1,} 2-dimethyl-2- ^phenoxy-yl lazirid ⁱ nu te ^p lot ^of boiling 5 ^6-60 ° C ^{at t} varnish 5 and ³ ^ ^p.

Example 18

Heat 10 g of N-methylstyrol and 10 C of carbon tetrachloride at reflux.

Once the mixture has started to boil, a solution of 340 mmol of N, N-dibromo-n-butylamine in 250 ml of carbon tetrachloride is added dropwise and the solution stops heating because of the slow boiling effect of the reaction heat. The solution is cooled and the resulting 1'-butyl-2-methyl-2-phenylaziridine isolated by extraction with cold 2 N sulfuric acid. . alkalization and ether extraction. Yield: 52%. 34 g of said Aziri ^di nu te rt ^{pl of} boiling ^72nd and ⁷⁵ ° ^C and ^{at pressure to 13} at ³³ mbar. .

Example 19

A solution of 100 mmol of Ν, Ν-dichiorailylemine and 400 mmol of styrene in 150 ml of carbon tetrachloride was allowed to stand at room temperature for 2 days. After this time, the oxidizing capacity of the solution disappears completely. After extraction with cold 2 M sulfuric acid, basification and extraction with ether, isolated in this manner in a yield of 38% of the theoretical amount of 6.1 g l-allyl--fenylazirtdinu ^t e ^pl of about ^the boiling point of ⁴ to 57 5 ° ^C and ^{at pressure} in ^{the 26,6} Pa.

Claims (1)

A process for the preparation of aziridines of the general formula I R ⁵ (I) wherein R ¹ , R ² , R ³ and R ⁴ are hydrogen, alkyl of 1 to 10 carbon atoms, 198,523 phenyl or alkoxyphenyl having 1 to 3 carbon atoms in alkoxyekupinČ, wherein the groups R1 _ C - C - R \ or R ² '- C - C - R optionally form part. cykloallfatického ring of 5 to 7 atoms in ^HLI ku and R represents ^and atom of a ^thank u and ^{plurality of projections} nominal s ^to u ^P inu ^{1 and} 4 atoms in ^hlík u or a cycloalkyl group of 5-7 carbon atoms, from an olefin of the general of formula II (II), w ^e R ^1, R ^{2, R} 3 and R ^s maj svrc ^h at defined, ^wherein characterized by the Hm ^'Z e is ^{fi l} e n ^y o ^{b s} ECN ho'vzorce II are reacted with an N-halogenated compound of formula III or a compound of formula IV R ⁵ -NH ^- X (III) R ⁵ - NH-, (IV), wherein ^R, m ^{and h} in svrc defined and ^χ represents C ^{and the} atom ^{b hl} oru not of bromine in the organic Oust extended ^{p d t} le EPLO at 0-15 ° C, preferably at room temperature, and the aziridine so formed is isolated from the reaction mixture.