DE1085145B - Process for the decomposition of racemic tropic acid into its optically active components - Google Patents

Process for the decomposition of racemic tropic acid into its optically active components

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Publication number
DE1085145B
DE1085145B DEE17402A DEE0017402A DE1085145B DE 1085145 B DE1085145 B DE 1085145B DE E17402 A DEE17402 A DE E17402A DE E0017402 A DEE0017402 A DE E0017402A DE 1085145 B DE1085145 B DE 1085145B
Authority
DE
Germany
Prior art keywords
tropic acid
optically active
active components
decomposition
acid
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
DEE17402A
Other languages
German (de)
Inventor
Dr-Chem Gabor Fodor
Ggoergy Csepreghy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Egyt Gyogyszervegyeszeti Gyar
Original Assignee
Egyt Gyogyszervegyeszeti Gyar
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 Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar
Publication of DE1085145B publication Critical patent/DE1085145B/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C07D451/06—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
    • C07C59/48—Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings

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

Description

DEUTSCHESGERMAN

Die linksdrehende Modifikation der Tropasäure stellt einen wichtigen Bestandteil mehrerer Alkaloide und synthetischer Arzneimittel, wie des optisch aktiven Tropins (Hyosciamins), ferner des optisch aktiven Scopolamins (Hyoscins), dar. Das neuerdings in die Therapie eingeführte N-Butyl-scopolaminbromid enthält ebenfalls linksdrehende Tropasäure.The levorotatory modification of tropic acid is an important component of several alkaloids and synthetic drugs, such as the optically active tropine (hyosciamine), and also the optically active scopolamine (Hyoscins). The recently introduced into therapy also contains N-butyl-scopolamine bromide levorotatory tropic acid.

Es sind bereits mehrere Verfahren bekannt, um racemische Tropasäure unter Verwendung von- Chinin, Chinidin, Morphin, Äthylhydrocupreidin, Äthylhydrocuprein, Cinchotoxin und Chinotoxin in die optisch aktiven Antipoden zu zerlegen (vgl. »Berichte der Deutschen Chemischen Gesellschaft«, Bd. 22, S. 2591; »Journal of the Chemical Society«, London, Bd. 121, S. 2582 bis 2586, und Bd. 115, S. 838 bis 840).There are already several methods known to racemic Tropic acid using quinine, quinidine, morphine, ethylhydrocupreidine, ethylhydrocupreine, To break down cinchotoxin and quinotoxin into the optically active antipodes (cf. »reports of German Chemical Society ", Vol. 22, p. 2591; Journal of the Chemical Society, London, Vol. 121, Pp. 2582 to 2586, and vol. 115, pp. 838 to 840).

Bei diesen Verfahren wird stets zunächst das diastereomere Salz der rechtsdrehenden (H-)-Tropasäure ausgeschieden, die für die Herstellung von pharmazeutischen Produkten wertlos ist. Das wertvollere diastereomere Salz der linksdrehenden Modifikation verbleibt dagegen in ao der Mutterlauge, aus der es nur nach mehrmaliger umständlicher fraktionierter Kristallisation isoliert werden kann. Aus diesem Grunde sind die bekannten Verfahren für die Herstellung von (—)-Tropasäure in technischem Maßstab nicht geeignet.In this process, the diastereomeric salt of the dextrorotatory (H -) - tropic acid is always excreted first, which is worthless for the manufacture of pharmaceutical products. The more valuable diastereomeric salt the counter-clockwise modification, however, remains in ao of the mother liquor, from which it only becomes more complicated after several times fractional crystallization can be isolated. For this reason, the known methods not suitable for the production of (-) - tropic acid on an industrial scale.

Es wurde nun gefunden, daß die racemische Tropasäure über ihre stereomeren Salze mit optisch aktivem threol-(p-Nitrophenyl)-2-amino-l,3-propandiol sehr leicht in die optischen Antipoden zerlegt werden kann, wobei sich bei Anwendung von d(—)-threo-l-(p-Nitrophenyl)-2-amino-l,3-propandiol das stereomere Salz der (—)-Tropasäure in kristalliner Form leicht abscheidet und bei Anwendung von L(+)-l-threo-l-(p-Nitrophenyl)-2-amino-1,3-propandiol das stereomere Salz der (+)-Tropasäure sich in kristalliner Form isolieren läßt.It has now been found that the racemic tropic acid via its stereomeric salts with optically active threol- (p-nitrophenyl) -2-amino-1,3-propanediol can very easily be broken down into the optical antipodes, with the use of d (-) - threo-l- (p-nitrophenyl) -2-amino-1,3-propanediol the stereomeric salt of (-) - tropic acid easily separates in crystalline form and at Use of L (+) - l-threo-l- (p-nitrophenyl) -2-amino-1,3-propanediol the stereomeric salt of (+) - tropic acid can be isolated in crystalline form.

Aus den getrennten diastereomeren Salzen kann die optisch aktive Tropasäure in einfacher Weise, großer Reinheit und sehr guter Ausbeute in an sich bekannter Weise gewonnen werden.The optically active tropic acid can be obtained from the separated diastereomeric salts in a simple, large manner Purity and very good yield can be obtained in a manner known per se.

Verfahren zur ZerlegungProcedure for dismantling

von racemischer Tropasäureof racemic tropic acid

in ihre optisch aktiven Komponenteninto their optically active components

Anmelder:Applicant:

Egyesült Gyogyszer- es Tapszergyär,
BudapestEgyesält Gyogyszer- es Tapszergyär,
Budapest

Vertreter:Representative:

Dr. G. W. Lotterhos und Dr.-Ing. H. W. Lotterhos,
Patentanwälte, Frankfurt/M., Lichtensteinstr. 3Dr. GW Lotterhos and Dr.-Ing. HW Lotterhos,
Patent attorneys, Frankfurt / M., Lichtensteinstr. 3

Beanspruchte Priorität:
Ungarn vom 31. März 1958Claimed priority:
Hungary from March 31, 1958

Dr.-Chem. Gabor Fodor und Ggörgy Csepreghy,Dr.-Chem. Gabor Fodor and Ggörgy Csepreghy,

Budapest,
sind als Erfinder genannt wordenBudapest,
have been named as inventors

Beispiel 1example 1

26,7 g racemische Tropasäure und 34 g d(—)-threol-(p-Nitrophenyl)-2-amino-l,3-propandiol werden in 275 ecm Wasser von 40 bis 50° C gelöst. Die Lösung wird filtriert und das Filtrat mit Kristallen des Aminoalkohols geimpft. Die Lösung läßt man nun bei einer Temperatur von etwa 20 bis 25° C über Nacht stehen. Nach ungefähr 10 bis 15 Stunden kristallisiert in schönen Kristallen das aus (—)-Tropasäure und d(—)-threo-l-(p-Nitrophenyl)-2-amino-l,3-propandiol gebildete diastereomere Salz aus. Es wird abfiltriert, zweimal mit 15 ecm Eiswasser gewaschen und getrocknet. Ausbeute 27 g (=90%); F. = 107° C.26.7 g of racemic tropic acid and 34 g of d (-) - threol- (p-nitrophenyl) -2-amino-1,3-propanediol are dissolved in 275 ecm of water at 40 to 50 ° C. The solution is filtered and the filtrate with crystals of the amino alcohol vaccinated. The solution is then left to stand at a temperature of about 20 to 25 ° C. overnight. After about 10 to 15 hours crystallizes from (-) - tropic acid and d (-) - threo-1- (p-nitrophenyl) -2-amino-1,3-propanediol in beautiful crystals formed diastereomeric salt. It is filtered off, washed twice with 15 ecm of ice water and dried. Yield 27 g (= 90%); F. = 107 ° C.

Zur Gewinnung von (—)-Tropasäure werden 27 g des erhaltenen Salzes in 25 ecm Wasser unter Erwärmen gelöst und bei etwa 80° C mit 15 ecm konz. wäßrigem Ammoniak versetzt. Beim Abkühlen der Lösung fällt die Aminopropandiolbase kristallin aus und wird abfiltriert. Die Lösung wird, falls nötig, mit Tierkohle entfärbt und die farblose Lösung mit Salzsäure angesäuert. Beim Abkühlen fällt die (—)-Tropasäure aus, die abfiltriert wird. Durch Einengen der Mutterlauge bei vermindertem Druck kann man noch weitere Mengen (—)-Tropasäure gewinnen. Die erhaltene (—)-Tropasäure wird mit 10 ecm Eiswasser gewaschen und getrocknet. Ausbeute: 10 g (-)-Tropasäure (=77%); F. = 128° C; [a]f = -72°.To obtain (-) - tropic acid, 27 g of the salt obtained are heated in 25 ecm of water dissolved and at about 80 ° C with 15 ecm conc. aqueous ammonia added. When the solution cools, it falls the aminopropanediol base crystallizes out and is filtered off. If necessary, the solution is decolorized with animal charcoal and acidified the colorless solution with hydrochloric acid. On cooling, the (-) - tropic acid precipitates and is filtered off will. Further amounts can be obtained by concentrating the mother liquor under reduced pressure (-) - gain tropic acid. The (-) - tropic acid obtained is washed with 10 ecm of ice water and dried. Yield: 10 g of (-) - tropic acid (= 77%); Mp = 128 ° C; [a] f = -72 °.

Beispiel 2Example 2

Man verfährt in der im Beispiel 1 beschriebenen Weise, mit dem Unterschied, daß man als Base L(+)-threol-(p-Nitrophenyl)-2-amino-l,3-propandiolverwendet.Man erhält das diastereomere Salz der (-f-)-Tropasäure und des l(+) -threoj-1 - (p-Nitrophenyl)-2-amino-l,3-propandiols. Ausbeute: 27 g; F. = 107° C. Die Spaltung zuThe procedure described in Example 1 is repeated, with the difference that L (+) - threol- (p-nitrophenyl) -2-amino-1,3-propanediol is used as the base receives the diastereomeric salt of (-f -) - tropic acid and des l (+) -threoj-1 - (p-nitrophenyl) -2-amino-1,3-propanediol. Yield: 27 g; F. = 107 ° C. The cleavage too

009 550/341009 550/341

Claims (1)

3 43 4 (-f-)-Tropasäure erfolgt, wie im Beispiel 1 für die links- Bildung von diastereomeren Salzpaaren mittels einer(-f -) - Tropic acid takes place, as in Example 1 for the left formation of diastereomeric salt pairs by means of a drehende Tropasäure angegeben wurde. optisch aktiven Base, anschließende Trennung dieserrotating tropic acid was given. optically active base, subsequent separation of these Salzpaare durch fraktionierte Kristallisation und ihreSalt pairs by fractional crystallization and their Patentanspruch: Zerlegung, dadurch gekennzeichnet, daß man alsClaim: dismantling, characterized in that as Verfahren zur Zerlegung von racemischer Tropa- 5 optisch aktive Base d(—)- oder L(+)-threo-l-(p-Nitro-Process for the resolution of racemic tropa- 5 optically active base d (-) - or L (+) - threo-l- (p-nitro- säure in ihre optisch aktiven Komponenten durch phenyl)-2-amino-l,3-propandiol verwendet.acid is used in its optically active components by phenyl) -2-amino-l, 3-propanediol. © 009 550/341 7.60© 009 550/341 7.60
DEE17402A 1958-03-31 1959-03-28 Process for the decomposition of racemic tropic acid into its optically active components Pending DE1085145B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HU1085145X 1958-03-31

Publications (1)

Publication Number Publication Date
DE1085145B true DE1085145B (en) 1960-07-14

Family

ID=11003145

Family Applications (1)

Application Number Title Priority Date Filing Date
DEE17402A Pending DE1085145B (en) 1958-03-31 1959-03-28 Process for the decomposition of racemic tropic acid into its optically active components

Country Status (1)

Country Link
DE (1) DE1085145B (en)

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