WO2005097736A1 - Procede pour preparer des azidoalkylamines - Google Patents

Procede pour preparer des azidoalkylamines Download PDF

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Publication number
WO2005097736A1
WO2005097736A1 PCT/EP2005/003655 EP2005003655W WO2005097736A1 WO 2005097736 A1 WO2005097736 A1 WO 2005097736A1 EP 2005003655 W EP2005003655 W EP 2005003655W WO 2005097736 A1 WO2005097736 A1 WO 2005097736A1
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WO
WIPO (PCT)
Prior art keywords
amine
azide
bromo
water
azidoalkylamine
Prior art date
Application number
PCT/EP2005/003655
Other languages
German (de)
English (en)
Inventor
Jan Haller
Original Assignee
Dynamit Nobel Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dynamit Nobel Gmbh filed Critical Dynamit Nobel Gmbh
Priority to US11/547,722 priority Critical patent/US20080039613A1/en
Priority to EP05736801A priority patent/EP1735272A1/fr
Priority to JP2007506725A priority patent/JP2007532505A/ja
Publication of WO2005097736A1 publication Critical patent/WO2005097736A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C247/00—Compounds containing azido groups
    • C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C247/04—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being saturated

Definitions

  • the invention relates to a process for the preparation of azidoalkylamines.
  • Azidoalkylamines play an important role as intermediates in organic synthesis.
  • azidoalkylamines are particularly problematic when additional positions on the amino group can be substituted. Either a poor yield or complex protection group technology has to be accepted.
  • JP 2002-332274 describes such a synthesis in which the amino groups are protected. This makes the synthesis very complex and the yield across all stages is below 40%.
  • the object of the invention is to overcome the disadvantages of the prior art and in particular to provide a process for the preparation of azidoalkylamines which delivers good yields with relatively little effort.
  • the object is achieved by a method with the characteristics of the main claim.
  • a bifunctional alkane with two different nucleofugic groups is reacted with an azide with elimination of a nucleofugic group to form a monofunctional azidoalkane.
  • the monofunctional azidoalkane is reacted with a primary or secondary amine to split off the second nucleofugic group to give the azidoalkylamine.
  • a bifunctional alkane is understood here to mean a compound which contains two different nucleofugic groups, in which each of the two nucleofugic groups is bonded to a primary, secondary or tertiary alkyl group and the two alkyl groups are connected to one another directly or via one or more intermediate members Z.
  • the monofunctional azidoalkane obtained in the first stage e.g. an azidochloroalkane
  • a primary or secondary amine without a prior exchange reaction being necessary (e.g. the less nucleofugic group chlorine is exchanged for a more reactive group such as iodine).
  • the monofunctional azidoalkane is reacted with an amine, it is not the double-azidoalkylated product but almost exclusively the desired single-azidoalkylated product.
  • G 1 nucleofuge group 1
  • G 2 nucleofuge group 2
  • n natural number from 1 to 20, preferably from 2 to 10, particularly preferably from 3 to 6.
  • R, R ' alkyl having 1 to 20, preferably 2 to 10, particularly preferably 3 to 6 C atoms or functionalized alkyl having 1 to 20, preferably 2 to 10, particularly preferably 3 to 6 C atoms, where R and R '' can also be connected to form a ring, for example with the following functional groups (non-restrictive list):
  • Alkenyl, alkynyl, aryl or heterocycle Alkenyl, alkynyl, aryl or heterocycle.
  • R 11 , R 1 ", R IV and R v independently of one another H, alkyl, aryl, also linked to one another to form a ring;
  • Z can also be omitted, in which case the two carbon atoms in the above formula are directly linked to one another.
  • Nucleofuge groups can e.g. be: chloride, bromide, iodide or sulfonates (such as methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate).
  • the nucleofugic group with the higher reactivity is substituted in the first reaction step (process step) by the azide group, while the nucleofugic group with the lower reactivity is only substituted in the second reaction step (process step) by the primary or secondary amine.
  • 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-iodobutane, 1-chloro-5 -iodpentane, 1-chloro-6-iodohexane, p-toluenesulfonic acid 2-chloroethyl ester, methanesulfonic acid 2-chloroethyl ester, p-toluenesulfonic acid 3-chloropropyl ester.
  • the first stage of the process is carried out in a polar solvent, e.g. Formamide, dimethylformarnide, dimethylacetamide, dimethyl sulfoxide, diethylene glycol, methanol, acetone or water.
  • a polar solvent e.g. Formamide, dimethylformarnide, dimethylacetamide, dimethyl sulfoxide, diethylene glycol, methanol, acetone or water.
  • Mixtures of these solvents in particular an organic solvent and water, can also be used.
  • Such a mixture preferably contains at most 30% by weight of water.
  • Those solvents are particularly preferred in which both the bifunctional alkane and the azide are at least 1% by weight soluble.
  • the azidoalkane which still contains a nucleofugic group, can - but does not have to - be purified before it reacts with the primary or secondary amine to form the azidoalkylamine.
  • the intermediate connection is preferred with a extracted non-polar solvent from the polar solvent of the first stage. It is particularly preferred to add water after the addition of the non-polar solvent.
  • the primary or secondary amine is preferably used in excess in the second process step.
  • the excess is particularly preferably 1 to 5000 mol%, in the case of monoamines preferably 10 to 100 mol% and in the case of polyvalent amines, such as diamines, preferably 100 to 1000 mol%.
  • the primary amine is a diamine and only one amino group is to be azidoalkylated, an excess of the diamine is used or this is used simultaneously as a solvent.
  • Water is preferably added before, during or after the reaction with the amine, or a water-containing amine is used.
  • the amount of water present in the reaction is preferably 5 to 90% by weight of the total amount of amine and water, particularly preferably 15 to 50% by weight.
  • the azidoalkylamine can be separated from the excess amine using an apolar solvent and distilled.
  • the azidoalkylamine can be precipitated as a salt by adding an acid and can be further purified by recrystallization.
  • N- (azidoalkyl) diaminoalkanes can be worked up in this way.
  • the azidoalkylamine is preferably fractionally precipitated by first precipitating the excess, unreacted amine with the required amount of acid and separating it before the azidoalkylamine is precipitated with acid.
  • the azidoalkylamine obtained can be purified by chromatography as a free base, as a salt of the acid which is released in the reaction in the second stage, or as a salt of precipitation with an acid.
  • the azidoalkylamine obtained can also be separated off and / or purified by distillation.
  • the invention is illustrated by the following examples, without restricting it:
  • 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
  • the 1-azido-4-chlorobutane isolated from the hexane extract by distilling off the solvent has an extremely high decomposition energy of 4000 J / g and is sensitive to impact!
  • Example 2 Preparation of N- (4-azidobutyl) -1,3-propanediamine with addition of water and precipitation as N- (4-azidobutyl) -1,3-propanediammonium bis-methanesulfonate
  • Example 3 Preparation of N- (4-azidobutyl) -1,3-propanediamine using water-containing 1,3-diaminopropane and precipitation as N- (4-azidobutyl) -1,3-propanediammonium bismethanesulfonate
  • the mixture was stirred at room temperature for 1 hour, warmed to 35 ° C., the hexane was distilled off in vacuo and the mixture was stirred at 35 ° C. for a further 4 hours.
  • the cooled, cloudy solution was extracted twice with 10 ml of toluene and the product was fractionally precipitated from the toluene phase by adding 5.4 g of methanesulfonic acid.
  • the solid was washed with acetonitrile and recrystallized from 50 ml of isopropanol.
  • Example 4 Preparation of N- (4-A_zidobutyl) -1,3-propanediamine and precipitation as N- (4-azidobutyl) -1,3-propanediarrimonium bismethanesulfonate
  • IR (KBr): v (cm "1 ) 2932, 2870, 2797, 2453, 2091, 1593, 1462, 1261.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé pour préparer des azidoalkylamines, comprenant une première étape au cours de laquelle un alcane bifonctionnel comprenant des groupes différemment nucléofuges, est converti avec un acide, en un azidoalcane monofonctionnel, par séparation d'un groupe nucléofuge, et une seconde étape au cours de laquelle l'azidoalcane monofonctionnel est converti avec une amine primaire ou secondaire, en azidoalkylamine, par séparation du second groupe nucléofuge.
PCT/EP2005/003655 2004-04-07 2005-04-07 Procede pour preparer des azidoalkylamines WO2005097736A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US11/547,722 US20080039613A1 (en) 2004-04-07 2005-04-07 Process for the Production of Azidoalkylamines
EP05736801A EP1735272A1 (fr) 2004-04-07 2005-04-07 Procede pour preparer des azidoalkylamines
JP2007506725A JP2007532505A (ja) 2004-04-07 2005-04-07 アジドアルキルアミンの製造方法

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE102004017607 2004-04-07
DE102004017607.8 2004-04-07
DE102004045870A DE102004045870A1 (de) 2004-04-07 2004-09-20 Verfahren zur Herstellung von Azidoalkylaminen
DE102004045870.7 2004-09-20

Publications (1)

Publication Number Publication Date
WO2005097736A1 true WO2005097736A1 (fr) 2005-10-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/003655 WO2005097736A1 (fr) 2004-04-07 2005-04-07 Procede pour preparer des azidoalkylamines

Country Status (4)

Country Link
EP (1) EP1735272A1 (fr)
JP (1) JP2007532505A (fr)
DE (1) DE102004045870A1 (fr)
WO (1) WO2005097736A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2315802A4 (fr) * 2008-07-31 2012-04-18 3M Innovative Properties Co Compositions d'azoture et leurs procédés de préparation et d'utilisation
CN115108874B (zh) * 2021-03-18 2023-09-08 中国科学院福建物质结构研究所 一种胺叠氮手性化合物、双叠氮手性化合物以及相关制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102816194A (zh) * 2004-02-27 2012-12-12 瑞伯-X医药品有限公司 大环化合物以及其制作和使用方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BELL, RUSSELL A. ET AL: "The total synthesis of a technetium chelate- tamoxifen complex", CANADIAN JOURNAL OF CHEMISTRY, 77(1), 146 -154 CODEN: CJCHAG; ISSN: 0008-4042, 1999, XP008049241 *
CARBONI, BERTRAND ET AL: "Aliphatic amino azides as key building blocks for efficient polyamine syntheses", JOURNAL OF ORGANIC CHEMISTRY , 58(14), 3736 -41 CODEN: JOCEAH; ISSN: 0022-3263, 1993, XP002334099 *
JEON, JOONG WON ET AL: "Toward protein-cleaving catalytic drugs: artificial protease selective for myoglobin", BIOORGANIC & MEDICINAL CHEMISTRY , 11(13), 2901 -2910 CODEN: BMECEP; ISSN: 0968-0896, 2003, XP002334100 *
LEBRETON, LUC ET AL: "Structure-Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 2. Structural Modifications of the Spermidine Moiety", JOURNAL OF MEDICINAL CHEMISTRY , 42(23), 4749 -4763 CODEN: JMCMAR; ISSN: 0022-2623, 1999, XP002334101 *

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Publication number Publication date
DE102004045870A1 (de) 2005-12-01
EP1735272A1 (fr) 2006-12-27
JP2007532505A (ja) 2007-11-15

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