DE102004045870A1 - Process for the preparation of azidoalkylamines - Google Patents

Abstract

A process for the preparation of azidoalkylamines is described in which, in the first process stage, a bifunctional alkane containing two different nucleofuge groups reacts with an azide with elimination of a nucleofugic group to form the other nucleofuge group-containing azidoalkane, and in the second stage that another nucleofuge group-containing azidoalkane reacts with a primary or secondary amine with elimination of the second nucleofugic group to Azidoalkylamin.

Description

The The invention relates to a process for the preparation of azidoalkylamines.

Azidoalkylamine play an important role as intermediates in organic synthesis.

The Synthesis of alkyl azides by nucleophilic substitution is known. The corresponding starting compound reacts with an azide.

In J. Org. Chem. 1957, 22, 238-240 describes the synthesis of alkyl azides starting from alkyl bromides and iodides in alcohols or 2-alkoxyethanols described with the addition of water. The alkyl azides carry no further functional groups.

In Tetrahedron Lett. 1991, 32, 183-186 describes the preparation of diazidoalkanes from the corresponding dichloro or dibromo derivatives in dimethylformamide described.

In J. Org. Chem. 1957, 22, 995-996 discloses the synthesis of 2-chloroethyl azide starting from 2-chloroethyl p-toluenesulfonate in a mixture of Methanol and water described. The reaction mixture is 24 hours under reflux and the product is then extracted and distilled.

In J. Org. Chem. 1993, 58, 3736-3741 describes the synthesis of azidoalkylamines and N- (azidoalkyl) diaminoalkanes, wherein N- (haloalkyl) -amines or diaminoalkanes serve as intermediates. These own the Disadvantage that your synthesis is complicated and that through can cyclize intramolecular substitution. Especially at the Synthesis of N- (4-azidobutyl) -1,3-propanediamine yields in the last step only at 30%, because the ring-closing nucleophilic substitution to N- (3-aminopropyl) -pyrrolidine comes to the fore. Furthermore the synthesis of azidobutylamines by aminolysis of 1-azido-4-iodobutane described. This in turn will be in two stages through the reaction of 1-bromo-4-chlorobutane with sodium azide to 1-azido-4-chlorobutane and the activation of the nucleophilic group chloride by their exchange prepared against iodide.

The Synthesis of azidoalkylamines is particularly troublesome if further positions on the amino group can be substituted. Either must be a poor yield or elaborate protection group technology be accepted.

The JP 2002-332274 describes such a synthesis in which the amino groups protected become. As a result, the synthesis becomes very complicated and the yield above all Levels is below 40%.

task The invention is to overcome the disadvantages of the prior art and in particular a process for the preparation of azidoalkylamines to create which with relatively little effort good yields supplies.

The The object is achieved by a process for the preparation of azidoalkylamines solved, in the first step, a bifunctional alkane, containing two different nucleofugic groups, with one azide with the splitting off of a nucleophilic group to the still other nucleofuge Group containing azidoalkane reacts, and in the second stage the azidoalkane containing the other nucleofugic group with a primary or secondary Amin reacted with elimination of the second nucleofugic group to Azidoalkylamin.

A bifunctional alkane is understood here to mean a compound in which each of the two nucleofugic groups is bonded to a primary, secondary or tertiary alkyl group and the two alkyl groups are directly connected to one another or connected to one another via one or more intermediate members. Intermediates Z may be, for example: saturated or unsaturated hydrocarbon chains, aryl groups, saturated or unsaturated carbocycles, which also bridge members such as -O-, -S-, -C (= O) -, -CO ₂ -, -SO ₂ - and not may contain reactive substituents such as ester, amide or ether groups.

Surprisingly, it has been found that, in the reaction of the azidoalkane containing a nucleofugic group with a primary or secondary amine, not the doubly azidoalkylated product is formed, but almost exclusively the desired azido-alkylated product is formed. It is furthermore surprising that the simple azidoalkylated product (for example an azidochloroalkane) obtained in the first stage reacts with a primary or secondary amine without a prior exchange reaction being carried out (for example the few nucleofuge group chlorine is exchanged for a more reactive group such as iodine).

mit:
G¹ = nucleofuge Gruppe 1
G² = nucleofuge Gruppe 2
n = natürliche Zahl von 1 bis 20, bevorzugt von 2 bis 10, besonders bevorzugt von 3 bis 6.
M = Metall, bevorzugt einwertiges Metall wie Li, Na, K, Rb, Cs; im Falle eines mehrwertigen Metalls ist die Formel MN₃ entsprechend anzupassen, z.B. M(N₃)₂ im Falle eines 2-wertigen Metalls wie Ba, Zn, oder M(N₃)₃ im Falle eines 3-wertigen Metalls wie Al; M = Ammonium, auch mit organischen Substituenten, wobei bis zu vier H-Atome des Ammoniumions durch (auch verschiedene) organische Reste (wie Methyl, Ethyl, Propyl, Butyl, Benzyl) substituiert sein können, z.B. (NH₄)⁺, (NMe₃H)⁺, (NEt₃H)⁺, (NBu₄)⁺ oder (NMe₃CH₂Ph)⁺; oder substituiertes Metall oder Halbmetall, z.B. MN₃= SiMe₃N₃, SnBu₃N₃, AlEt₂N₃.
R, R' = Alkylreste mit 1 bis 20, bevorzugt 2 bis 10, besonders bevorzugt 3 bis 6 C-Atomen oder funktionalisierte Alkylreste entsprechender Kettenlänge, wobei R und R' auch zu einem Ring verbunden sein können, mit z.B. folgenden funktionellen Gruppen (beispielhafte, nicht einschränkende Aufzählung):
Amin,
-OR¹ mit {R¹ = H, Alkyl, Alkenyl, Alkinyl, Aryl, Heterocyclus, -C(=O)R², -C(=S)R² mit [R² = Alkyl, Alkenyl, Alkinyl, Aryl, Heterocyclus, Alkoxy, Aryloxy, Heterocyclyloxy, -NR³R⁴ mit (R³ und R⁴ unabhängig voneinander = H, Alkyl, Alkenyl, Alkinyl, Aryl, Heterocyclus, wobei R³ und R⁴ auch zu einem Ring verknüpft sein können), -SR⁵ mit (R⁵ = Alkyl, Alkenyl, Alkinyl, Aryl, Heterocyclus)]},
-NR⁶R⁷ mit R⁶ und R⁷ unabhängig voneinander = R¹ wie zuvor definiert und zusätzlich -SO₂R⁵, wobei R⁶ und R⁷ auch zu einem Ring verknüpft sein können;
-N=CR⁸R⁹ mit R⁸ und R⁹ unabhängig voneinander = R² wie zuvor definiert, wobei R⁸ und R⁹ auch zu einem Ring verknüpft sein können,
-SR¹⁰ mit R¹⁰ = R¹ wie zuvor definiert aber ohne H;
-C(=O)R¹¹, -C(=O)C(=O)R¹¹, -C(=NOR³)R¹¹, -SOR¹¹, -SO₂R¹¹, -P(=O)R¹¹R¹² mit R¹¹ und R¹² = R² wie zuvor definiert und zusätzlich -OH;
-BR¹³R¹⁴ mit R¹³ und R¹⁴ unabhängig voneinander = R⁵, OR³, NR³R⁴ wie zuvor definiert;
-SiR¹⁵R¹⁶R¹⁷ mit R¹⁵, R¹⁶ und R¹⁷ unabhängig voneinander = R⁵, OR³;
-SnR¹⁸ ₃ mit R¹⁸ = Alkyl;
-F; -CN; -N₃; -NO₂;
Alkenyl, Alkinyl, Aryl oder Heterocyclus.Schematically, the reaction sequence can be represented as follows (bifunctional alkane here contains as intermediates only unbranched, saturated hydrocarbon chains, second stage alternatively with a primary or secondary amine):

With:
G ¹ = nucleofugic group 1
G ² = nucleofugic group 2
n = natural number from 1 to 20, preferably from 2 to 10, particularly preferably from 3 to 6.
M = metal, preferably monovalent metal such as Li, Na, K, Rb, Cs; in the case of a polyvalent metal, the formula MN _{3 should} be adapted accordingly, eg M (N ₃ ) ₂ in the case of a divalent metal such as Ba, Zn or M (N ₃ ) ₃ in the case of a trivalent metal such as Al; M = ammonium, also with organic substituents, where up to four H atoms of the ammonium ion can be substituted by (also different) organic radicals (such as methyl, ethyl, propyl, butyl, benzyl), eg (NH ₄ ) ⁺ , (NMe ₃ H) ⁺ , (NEt ₃ H) ⁺ , (NBu ₄ ) ⁺ or (NMe ₃ CH ₂ Ph) ⁺ ; or substituted metal or semimetal, for example MN ₃ = SiMe ₃ N ₃ , SnBu ₃ N ₃ , AlEt ₂ N ₃ .
R, R '= alkyl radicals having 1 to 20, preferably 2 to 10, particularly preferably 3 to 6 C atoms or functionalized alkyl radicals of corresponding chain length, where R and R' can also be linked to form a ring having, for example, the following functional groups (exemplary , non-limiting list):
Amin,
-OR ¹ with {R ¹ = H, alkyl, alkenyl, alkynyl, aryl, heterocycle, -C (= O) R ² , -C (= S) R ² with [R ² = alkyl, alkenyl, alkynyl, aryl, Heterocycle, alkoxy, aryloxy, heterocyclyloxy, -NR ³ R ⁴ with (R ³ and R ⁴ independently of one another = H, alkyl, alkenyl, alkynyl, aryl, heterocycle, where R ³ and R ^{4 may} also be linked to a ring), -SR ⁵ with (R ⁵ = alkyl, alkenyl, alkynyl, aryl, heterocycle)]},
-NR ⁶ R ⁷ with R ⁶ and R ⁷ independently of one another = R ¹ as defined above and additionally -SO ₂ R ⁵ , where R ⁶ and R ^{7 may} also be linked to form a ring;
-N = CR ⁸ R ⁹ with R ⁸ and R ⁹ independently of one another = R ² as defined above, where R ⁸ and R ^{9 can} also be linked to form a ring,
-SR ¹⁰ with R ¹⁰ = R ¹ as previously defined but without H;
-C (= O) R ¹¹ , -C (= O) C (= O) R ¹¹ , -C (= NOR ³ ) R ¹¹ , -SOR ¹¹ , -SO ₂ R ¹¹ , -P (= O) R ¹¹ R ¹² with R ¹¹ and R ¹² = R ² as previously defined and additionally -OH;
-BR ¹³ R ¹⁴ with R ¹³ and R ¹⁴ independently = R ⁵ , OR ³ , NR ³ R ⁴ as previously defined;
-SiR ¹⁵ R ¹⁶ R ¹⁷ with R ¹⁵ , R ¹⁶ and R ¹⁷ independently = R ⁵ , OR ³ ;
-SnR ¹⁸ ₃ with R ¹⁸ = alkyl;
-F; -CN; -N ₃ ; NO ₂ ;
Alkenyl, alkynyl, aryl or heterocycle.

mit R^II, R^III, R^IV und R^V = unabhängig voneinander H, Alkyl, Aryl, untereinander auch zum Ring verknüpft;
Z = gesättigte oder ungesättigte Kohlenwasserstoffketten mit 1 bis 20 C-Atomen, bevorzugt 1 bis 4 C-Atome, Arylgruppen, gesättigte oder ungesättigte Carbocyclen, die weiterhin Brückenglieder wie -O-, -S-, -C(=O)-, -CO₂-, -SO₂- und nicht reagierende Substituenten, wie Ester-, Amid- oder Ethergruppen. Z kann auch wegfallen, dann sind die beiden C-Atome in obiger Formel unmittelbar miteinander verbunden.Alternatively, a compound belonging to the following general formula can be used as the bifunctional alkane:

with R ^II , R ^III , R ^IV and R ^V = independently of one another H, alkyl, aryl, are also linked to one another in the ring;
Z = saturated or unsaturated hydrocarbon chains having 1 to 20 carbon atoms, preferably 1 to 4 carbon atoms, aryl groups, saturated or unsaturated carbocycles, which further bridge members such as -O-, -S-, -C (= O) -, - CO ₂ -, -SO ₂ - and non-reactive substituents, such as ester, amide or ether groups. Z can also be omitted, then the two C atoms in the above formula are directly connected.

nucleofugic Groups (substituents) can e.g. chloride, bromide, iodide or sulfonates (such as methanesulfonate, Trifluoromethanesulfonate, p-toluenesulfonate). The nucleofugic group with the higher Reactivity is in the first reaction step (process step) by the azide group substituted while the nucleofugic group with the lower reactivity only in second reaction step (process step) by the primary or secondary Amine is substituted. Examples of bifunctional alkanes are 1-bromo-2-chloroethane, 1-bromo-3-chloropropane, 1-bromo-3-chloro-2-methylpropane, 1-bromo-4-chlorobutane, 1-bromo-5-chloropentane, 1-bromo-6-chlorohexane, 2-bromo-1-chloropropane, 1-bromo-3-chloro-2,2-dimethoxypropane, 1-chloro-3-iodopropane, 1-chloro-4-iodo-butane, 1-chloro-5-iodopentane, 1-chloro-6-iodohexane, p-toluenesulfonic acid 2-chloroethyl ester, Methane sulfonic acid 2-chloroethyl, p-toluenesulfonic acid-3-chlorpropylester. An example for a bifunctional alkane with aryl intermediate is 2- (chloromethyl) benzyl bromide.

Prefers becomes the first step of the process in a polar solvent carried out, such as. Formamide, dimethylformamide, dimethylacetamide, dimethyl sulphoxide, Diethylene glycol, methanol, acetone or water. It can too Mixtures of these solvents, used in particular by an organic solvent and water become. Preferably contains such a mixture at most 30% by weight of water. Particularly preferred are such solvents, where both the bifunctional alkane and the azide are at least with 1 wt .-% soluble are.

The but one must still contain a nucleofugic-containing azidoalkane not cleaned Be it with the primary before or secondary Amin reacts to Azidoalkylamin. The intermediate compound is preferred with a nonpolar solvent from the polar solvent extracted the first stage. Particularly preferred is a Addition of water after the addition of the nonpolar solvent.

Prefers in the second process step, the primary or secondary amine in excess used. Particularly preferably, the excess is from 1 to 5000 mol%, in the case of monoamines, preferably 10 to 100 mol% and in the case of polybasic amines, such as diamines, preferably 100 to 1000 mol%. Especially if it is at the primary Amine is a diamine and azidoalkylated only one amino group is going to be a surplus of the diamine or this at the same time as a solvent uses. Preference is given during or after the reaction with the amine added to water, or a hydrous amine used. The existing in the reaction Amount of water is preferably 5 to 90% by weight of the total amount of amine and water, especially preferably 15 to 50 wt .-%.

to Isolation of azidoalkylamine may be this extractive with a nonpolar solvent from the excess diamine be separated and distilled. The Azidoalkylamin can by Addition of an acid as Salt like and further purified by recrystallization. Especially N- (azidoalkyl) -diaminoalkane can to be worked up in this way. The azidoalkylamine is preferably included here like fractional, by first the excess, unreacted Amin with that required Amount of acid like and separated before acid precipitation of the azidoalkylamine.

The Azidoalkylamin obtained as the free base, as a salt of the acid, the released in the second stage reaction, or as Salt of the precipitate with an acid be purified by chromatography.

The Azidoalkylamin obtained can also be separated by distillation and / or getting cleaned.

Of the The invention is further illustrated by the following examples:

Example 1: Preparation of N- (4-azidobutyl) -1,3-diaminopropane with addition of water and fractional precipitation as N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate

To 27.1 g of sodium azide in 455 ml of dimethyl sulfoxide were added at room temperature 65 g of 1-bromo-4-chlorobutane. After stirring overnight at room temperature, a suspension was formed, which was treated with 250 ml of hexane and 455 ml of water. After phase separation, the aqueous phase was extracted with a further 125 ml of hexane. The combined organic phases were washed with 250 ml of water and treated with 140.5 g of 1,3-diaminopropane. After the metered addition of 40 ml of water, the hexane was distilled off at 35 ° C in vacuo and the mixture stirred for a further 5 hours at 35 ° C. The cooled reaction mixture was extracted successively with 390 ml and 130 ml of toluene. 515.5 g of toluene extract were obtained. From 250 g of the toluene phase, the main part of the 1,3-diaminopropane was fractionally precipitated according to the analytically determined content by the addition of 16.9 g of methanesulfonic acid as 1,3-Propandiammoniumbismethansulfonat. The solid was filtered off and washed with 30 ml of toluene and dried. There was obtained 24.2 g of a colorless solid containing 0.9% by weight of N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate. The main product was precipitated from the combined filtrates by metered addition of 22.3 g of methanesulfonic acid, filtered off and washed with 30 ml of toluene and twice with 30 ml of isopropanol each time. After drying the solid, 39.6 g of N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate were obtained as a colorless solid having a purity of 98.2% by weight (58% yield). By acidification to pH 3 with another 7.7 g of methanesulfonic acid, filtration, washing of the solid with toluene and isopropanol and drying, a further 11.5 g of product containing 80.6% by weight (14% yield) were obtained from the filtrate. N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate.
300 MHz ¹ H-NMR (CD ₃ OD): δ = 1.65-1.74 (m, 2H); 1.76-1.86 (m, 2H); 2.05-2.16 (m, 2H); 2.73 (s, 6H); 3.05-3.17 (m, 6H); 3.41 (t, 2H).
IR (KBr): ν (cm ^-1 ) = 3425, 2947, 2781, 2098, 1504, 1196, 1161, 1057, 783, 563, 536.
Melting point (DSC): 115 ° C; Decomposition (DSC): 217 ° C (onset).

Warning: The hexane extract by distilling off the solvent Isolated 1-azido-4-chlorobutane has an extremely high decomposition energy of 4000 J / g and is shock sensitive!

Example 2: Preparation of N- (4-azidobutyl) -1,3-propanediamine with the addition of water and precipitation as N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate

To 27.1 g of sodium azide in 260 ml of dimethylsulfoxide were added at room temperature 65 g of 1-bromo-4-chlorobutane metered. After two hours of stirring at room temperature a suspension which is mixed with 260 ml of hexane and with 260 ml of water has been. After phase separation, the aqueous phase was further 130 extracted hexane. The combined organic phases were washed with Washed 260 ml of water and treated with 140.4 g of 1,3-diaminopropane. After metering in 40 ml of water, the hexane was at 35 ° C in vacuo distilled off and the mixture for a further 4 hours at 35 ° C. touched. The cooled reaction mixture was successively with 390 ml and 130 Toluene extracted and the product from the toluene phase by addition of 120 g of methanesulfonic acid like. The solid was washed with 130 ml of isopropanol and with 730 ml of hot Extracted isopropanol. Crystallized from the cooled extract 69.4 g (56% yield) of N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate as a colorless solid with a purity of 95%. The product could be further purified by recrystallization from isopropanol / water become.

Example 3: Production of N- (4-azidobutyl) -1,3-propanediamine using hydrous 1,3-diaminopropane and precipitation as N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate

5 g of 1-bromo-4-chlorobutane were added at room temperature to 1.9 g of sodium azide in 20 ml of dimethyl sulfoxide. After stirring at room temperature overnight, a suspension was formed, which was treated with 20 ml of hexane and 20 ml of water. After phase separation, the aqueous phase was washed with an additional 20 ml of hexane extracted. The combined organic phases were washed with 20 ml of water and added to 9.7 g of 1,3-diaminopropane, which contained about 20 wt .-% water. The mixture was stirred for 1 hour at room temperature, heated to 35 ° C, the hexane distilled off in vacuo and the mixture stirred for a further 4 hours at 35 ° C. The cooled, turbid solution was extracted twice with 10 ml of toluene and the product from the toluene phase by the addition of 5.4 g of methanesulfonic fractionally precipitated. The solid was washed with acetonitrile and recrystallized from 50 ml of isopropanol. There was obtained 6.0 g (56% yield) of N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate as a colorless solid having a purity of 98.4%.

Example 4: Production of N- (4-azidobutyl) -1,3-propanediamine and precipitation as N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate

To 8 g of sodium azide in 80 ml of dimethyl sulfoxide were metered at 35 ° C 20 g of 1-bromo-4-chlorobutane. After two hours stir at 35 ° C A suspension was formed which, after cooling to room temperature with 77 ml of hexane and with 77 ml of water was added. After the phase separation became the watery Phase extracted with another 40 ml of hexane. The combined organic Phases were washed with 80 ml of water and with 43.2 g of 1,3-diaminopropane added. The mixture was warmed to 35 ° C, the hexane distilled off in vacuo and the mixture stirred for a further 4 hours at 35 ° C. This crystallized a colorless solid. The cooled mixture was twice treated with 40 ml of toluene and the main of 1,3-propanediamine hydrochloride existing solid separated. The product was passed through the toluene phase Addition of 21.5 g of methanesulfonic acid like. The solid was washed successively with 25 ml of toluene and 50 ml of isopropanol washed and in 450 ml of hot Isopropanol added. The insoluble Ingredients were filtered off. After cooling the filtrate From this, 19.8 g (56% yield) of N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate were obtained obtained as a colorless solid with a purity of 90.8% and further purified by recrystallization from isopropanol.

Example 5: Preparation of 4-azidodibutylamine hydrochloride

25 g of 1-bromo-4-chlorobutane were metered in at 25 to 28 ° C. to 10 g of sodium azide in 175 ml of dimethyl sulfoxide. After stirring overnight at room temperature, the mixture was treated with 100 ml of hexane and 175 ml of water, the separated aqueous phase was extracted with 50 ml of hexane and the combined organic phases were washed with 100 ml of water. There were obtained 113.4 g of a solution of 1-azido-4-chlorobutane in hexane. 17.5 g of this solution were mixed with 3.3 g of butylamine and 10 ml of ethanol and the hexane was distilled off at 30 ° C in vacuo. After four hours of stirring at 30 ° C, the reaction mixture was concentrated in vacuo and 4-Azidodibutylammoniumhydrochlorid by column chromatography on silica gel with dichloromethane / methanol. There was obtained 1.3 g (28% yield) of 4-azidodibutylammonium hydrochloride as a colorless solid.
300 MHZ- ¹ H-NMR (CD ₃ OD): δ = 1.00 (t, 3H); 1.37-1.48 (m, 2H); 1.62-1.76 (m, 6H); 2.90-2.98 (m, 4H); 3.39 (t, 2H).
IR (KBr): ν (cm ^-1 ) = 2932, 2870, 2797, 2453, 2091, 1593, 1462, 1261.

Claims (27)

Process for the preparation of Azidoalkylaminen, characterized in that in the first process stage, a bifunctional alkane containing two different nucleofuge groups reacts with an azide with elimination of a nucleofugic group to still the other nucleofugic group containing azidoalkane, and in the second process stage that the other nucleofuge-containing azidoalkane reacts with a primary or secondary amine with elimination of the second nucleofugic group to Azidoalkylamin. Method according to claim 1, characterized in that that the amine is a primary Amine is. A method according to claim 1 or 2, characterized in that the azide is a metal azide having a monovalent metal from the group Li, Na, K, Rb, Cs is. Method according to claim 1 or 2, characterized that the azide is a metal azide with a polyvalent metal from the Group Ba, Zn, Al is. Method according to claim 1 or 2, characterized that the azide is an ammonium azide, with up to four H atoms of the Ammonium nitrogen may be substituted by organic radicals. Method according to claim 1 or 2, characterized that the azide is a metal or semimetal azide in which the metal or the semimetal carries organic substituents. Method according to one of claims 1 to 6, characterized that the nucleofugic groups (substituents) are selected from: chloride, bromide, iodide and sulfonates. Method according to one of claims 1 to 7, characterized in that the bifunctional alkane is 1-bromo-2-chloroethane, 1-bromo-3-chloropropane, 1-bromo-3-chloro-2-methyl propane, 1-bromo-4-chlorobutane, 1-bromo-5-chloropentane, 1-bromo-6-chlorohexane, 2-bromo-1-chloropropane, 1-bromo-3-chloro-2,2-dimethoxypropane, 1-chloro-3-iodopropane, 1-chloro-4-iodo-butane, 1-chloro-5-iodopentane, 1-chloro-6-iodohexane, p-toluenesulfonic acid 2-chloroethyl ester, Methane sulfonic acid 2-chloroethyl, p-toluenesulfonic acid-3-chlorpropylester or 2- (chloromethyl) benzyl bromide is used. Method according to one of claims 1 to 8, characterized that the first stage of the process in a polar solvent carried out becomes. Method according to one of claims 1 to 8, characterized that the first stage of the process is carried out in a solvent, in which both the bifunctional alkane and the azide are at least 1% by weight soluble are. Method according to one of claims 9 or 10, characterized that as solvent formamide, Dimethylformamide, dimethylacetamide, dimethyl sulfoxide or diethylene glycol is used. Method according to one of claims 9 to 11, characterized that the intermediate compound with a nonpolar solvent from the polar solvent the first stage is extracted. Method according to claim 12, characterized in that that in the extraction of the intermediate compound after the addition of the nonpolar solvent additionally Added water becomes. Method according to one of claims 1 to 13, characterized that the intermediate compound without isolation as a pure substance with the amine is reacted. Method according to one of claims 1 to 14, characterized that in the second stage of the process the primary or secondary Amine in a surplus from 1 to 5000 mol% is used. Method according to claim 15, characterized in that that in the second stage of the process the primary or secondary Amine in a surplus from 10 to 100 mol% is used. Method according to one of claims 1 to 16, characterized the amine contains one or more further functional groups. Method according to one of claims 1 to 17, characterized that the amine is a diamine. Method according to claim 18, characterized that the diamine is in excess from 100 to 1000 mol% is used. Method according to one of claims 1 to 19, characterized that before, while or after the reaction with the amine added to water, or a hydrous amine is used. Method according to claim 20, characterized in that the amount of water present in the reaction amounts to 5 to 90% by weight based on the total amount of amine and water. Method according to claim 20, characterized in that the amount of water present in the reaction is 15 to 50% by weight based on the total amount of amine and water. Method according to one of claims 1 to 22, characterized the azidoalkylamine is an N- (azidoalkyl) diaminoalkane and extractive with a nonpolar solvent from the excess amine is separated. Method according to one of claims 1 to 23, characterized that the Azidoalkylamin is precipitated by addition of an acid. Method according to Claim 24, characterized that the Azidoalkylamin is fractionally precipitated by the addition of an acid. Method according to one of claims 1 to 25, characterized that the Azidoalkylamin obtained as the free base, as a salt with the Acid, which is released in the reaction in the second stage, or as Salt of the precipitate with an acid is purified by chromatography. Method according to one of claims 1 to 23, characterized that the Azidoalkylamin obtained separated by distillation and / or cleaned.