DE1059003B - Process for the preparation of primary basic diaryl alcohols - Google Patents

Process for the preparation of primary basic diaryl alcohols

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Publication number
DE1059003B
DE1059003B DER19150A DER0019150A DE1059003B DE 1059003 B DE1059003 B DE 1059003B DE R19150 A DER19150 A DE R19150A DE R0019150 A DER0019150 A DE R0019150A DE 1059003 B DE1059003 B DE 1059003B
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DE
Germany
Prior art keywords
lithium aluminum
primary
boiling
solvent
ether
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
DER19150A
Other languages
German (de)
Inventor
Dr Kurt Stach
Dipl-Chem Dr Phil Fritz Kurzen
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.)
Ravensberg GmbH Chemische Fabrik
Original Assignee
Ravensberg GmbH Chemische Fabrik
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 Ravensberg GmbH Chemische Fabrik filed Critical Ravensberg GmbH Chemische Fabrik
Priority to DER19150A priority Critical patent/DE1059003B/en
Publication of DE1059003B publication Critical patent/DE1059003B/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
    • C07C215/32—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton containing hydroxy groups and carbon atoms of two six-membered aromatic rings bound to the same carbon atom of the carbon skeleton

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

Description

DEUTSCHESGERMAN

Primäre basische Alkohole der allgemeinen FormelPrimary basic alcohols of the general formula

Ar1.Ar 1 .

Ar,Ar,

-[C]n-X- [C] n -X

CH2OH R2 CH 2 OH R 2

worin Ar1 und Ar2 Phenylreste, gegebenenfalls substituierte Phenylreste sein können, die Alkylgruppe (Cn) eine geradlinige (R1=R2=H) oder verzweigte Kette (R1=H, R2=niedriger Alkylrest oder R1 und R2 = niedriger Alkylrest) mit vorzugsweise 1 bis 4 Kohlenstoffatomen darstellt und der basische Substituent X, der seinen Sitz an einem der Arylkohlenwasserstoffe (Cn) hat, als primäres, sekundäres bzw. tertiäres oder cyclisches Amin vorliegt, lassen sich z. B. aus den entsprechenden Aldehyden durch katalytische Hydrierung (vgl. Yandik und L ar sen, J. Am. Chem. Soc, 73, S. 3534 [1951]) oder durch Reduktion der korrespondierenden Carbonsäureester mit Lithiumaluminiumhydrid gewinnen (Speeter et al., J. Am. Chem. Soc, 71, S. 57 [1949]). Die zuletzt genannten Autoren geben an, daß die Reduktion der entsprechenden Carbonsäuren mit Lithiumaluminiumhydrid nur geringe Ausbeuten an basischen primären Alkoholen ergibt.where Ar 1 and Ar 2 can be phenyl radicals, optionally substituted phenyl radicals, the alkyl group (Cn) is a straight (R 1 = R 2 = H) or branched chain (R 1 = H, R 2 = lower alkyl radical or R 1 and R 2 = lower alkyl radical) with preferably 1 to 4 carbon atoms and the basic substituent X, which is located on one of the aryl hydrocarbons (C n ), is present as a primary, secondary or tertiary or cyclic amine, can be, for. B. from the corresponding aldehydes by catalytic hydrogenation (see. Yandik and L ar sen, J. Am. Chem. Soc, 73, p. 3534 [1951]) or by reducing the corresponding carboxylic acid ester with lithium aluminum hydride (Speeter et al., J. Am. Chem. Soc, 71, p. 57 [1949]). The last-named authors state that the reduction of the corresponding carboxylic acids with lithium aluminum hydride gives only low yields of basic primary alcohols.

Es wurde nun überraschenderweise gefunden, daß die genannten pharmakologisch wirksamen basischen primären Alkohole in sehr guten Ausbeuten erhalten werden können, wenn man die Reduktion der entsprechenden Carbonsäuren mit Lithiumaluminiumhydrid in höhersiedenden organischen Lösungsmitteln, vorzugsweise Tetrahydrofuran, bei Siedetemperatur und unter mechanischer Rührung, durchführt. Selbst sterisch stark gehemmte Carbonsäuren, wie z. B. die a,a-Diphenyl-/8-methyl-4-dimethylamino-buttersäure, lassen sich glatt zu den entsprechenden primären Alkoholen, beispielsweise dem 1 - Dimethylamino - 2 - methyl-S^-diphenyl-butanol- (I) (der bisher nur durch Reduktion seines Aldehyds gewonnen wurde [vgl. Yandik, a.a.O.]) nach der vorher aufgezeigten Darstellungsweise umsetzen.It has now surprisingly been found that the pharmacologically active basic primary alcohols mentioned can be obtained in very good yields if the reduction of the corresponding carboxylic acids with lithium aluminum hydride is carried out in higher-boiling organic solvents, preferably tetrahydrofuran, at boiling temperature and with mechanical stirring. Even sterically hindered carboxylic acids, such as. B. the a, a-Diphenyl- / 8-methyl-4-dimethylamino-butyric acid, can be smoothly to the corresponding primary alcohols, for example the 1 - dimethylamino - 2 - methyl-S ^ -diphenyl-butanol- (I) ( which has so far only been obtained by reducing its aldehyde [see Yandik, loc. cit.]) according to the method of representation shown above.

Gemäß dem vorliegenden Verfahren sind nunmehr die basischen primären Aminoalkohole auf direktem Weg in einfacher und wirtschaftlicher Weise darstellbar, wobei gegenüber anderen Herstellungsmethoden ein wesentlicher technischer Fortschritt zu verzeichnen ist.According to the present process, the basic primary amino alcohols are now on direct Way can be represented in a simple and economical manner, with compared to other manufacturing methods significant technical progress has been made.

Die von Vogl und Pöhm (Mh. Chem., 83, S. 541 bis 543; 84, S. 1097 bis 1102) durchgeführte Reduktion von Aminocarbonsäuren mittels LiAlH4 in Tetrahydrofuran nimmt den Gegenstand der vorliegenden Erfindung in keiner Weise vorweg. Die von den genannten Autoren bearbeitete Gruppe von Ver-Verfahren zur Herstellung von primären basischen Diaryl-alkoholen The reduction of aminocarboxylic acids by means of LiAlH 4 in tetrahydrofuran carried out by Vogl and Pöhm (Mh. Chem., 83, pp. 541 to 543; 84, pp. 1097 to 1102) in no way anticipates the subject matter of the present invention. The group of processes for the production of primary basic diaryl alcohols worked on by the authors mentioned

Anmelder:Applicant:

Ravensberg G.m.b.H. Chemische Fabrik, Konstanz, Steinstr.27Ravensberg G.m.b.H. Chemical factory, Konstanz, Steinstrasse 27

Dr. Kurt Stach, Kreuzungen (Schweiz),Dr. Kurt Stach, Crossings (Switzerland),

und Dipl.-Chem. Dr. phil. Fritz Kurzen, Konstanz,
sind als Erfinder genannt wordenand Dipl.-Chem. Dr. phil. Fritz Kurzen, Constance,
have been named as inventors

bindungen unterscheidet sich nämlich von den erfindungsgemäß herzustellenden Verbindungen wesentlich. Vogl und Pöhm reduzieren natürlich vorkommende, einfache, vornehmlich α-Aminosäuren, welche die CO-Gruppe stets an eine CH-Bindung, in keinem einzigen Falle jedoch an ein quartäres C-Atom gebunden enthalten.This is because bonds differs significantly from the compounds to be produced according to the invention. Vogl and Pöhm reduce naturally occurring, simple, primarily α-amino acids, which the CO group is always bound to a CH bond, but never to a quaternary carbon atom contain.

Das quartäre C-Atom in Nachbarstellung zur CO-Gruppe ist für die Neuheit des vorliegenden Verfahrens von besonderer Bedeutung. Bekanntlich wirkt diese C-Bindung bei vielen Reaktionen, die sonst glatt verlaufen, durch sterische Hinderung stark hemmend, worauf z. B. Yandik und LarsenThe quaternary carbon atom in the vicinity of the CO group is for the novelty of the present process really important. It is well known that this C bond is effective in many reactions that otherwise occur run smoothly, strongly inhibiting by steric hindrance, whereupon z. B. Yandik and Larsen

(J. Am. Chem. Soc, 73, S. 3534 [1951], 1. Absatz, Zeilen 12 bis 15) bereits hingewiesen haben. Die geringen Ausbeuten von Yandik und Larsen bei der Li Al H4-Reduktion von basischen Alkyl-diarylnitrilen, die mit 31 bzw. 24% angegeben werden (a.a.O.), sowie von Speeter und Mitarbeiter (J. Am. Chem. Soc, 71, S. 57 [1949]) bei der Reduktion von y-Dimethylamino-a,a-diphenylvaleriansäure mit LiAlH4 in Äther, bestätigen dies. Es war deshalb nicht vorauszusehen, daß das erfindungsgemäße Verfahren unter Anwendung höhersiedender Lösungsmittel, wie Tetrahydrofuran, zu so überraschend hohen Ausbeuten führen würde.(J. Am. Chem. Soc, 73, p. 3534 [1951], 1st paragraph, lines 12 to 15) have already pointed out. The low yields of Yandik and Larsen in the Li Al H 4 reduction of basic alkyl diarylnitriles, which are given as 31 and 24%, respectively (loc. Cit.), And of Speeter and coworkers (J. Am. Chem. Soc, 71, P. 57 [1949]) in the reduction of γ-dimethylamino-a, a-diphenylvaleric acid with LiAlH 4 in ether, confirm this. It was therefore not foreseeable that the process according to the invention would lead to such surprisingly high yields using higher-boiling solvents such as tetrahydrofuran.

Gegenüber dem Stande der Technik liegt die Eigenartigkeit und Neuheit des vorliegenden Verf ahrens somit darin begründet, daß es mit diesem gelungen ist, durch ein quartäres C-Atom sterisch gehemmte basisch substituierte α,α-Diarylcarbonsäuren zu den entsprechenden Alkoholen nunmehr mit hoher Ausbeute zu reduzieren.Compared to the state of the art, the peculiarity and novelty of the present process lies thus based on the fact that it was possible to use this, sterically inhibited by a quaternary carbon atom basic substituted α, α-diarylcarboxylic acids to reduce to the corresponding alcohols now with high yield.

"■: ' ; -V 909 530/381"■: '; -V 909 530/381

Claims (1)

Beispielexample Zu 134 g α,α-Diphenyl-y-dimethylarninovaleriansäure und 2 1 Tetrahydrofuran trägt man unter Rühren bei Raumtemperatur 22 g Lithiumaluminiumtrydrid ein und erhitzt das Gemisch 15 Stunden zum Sieden. Anschließend werden nochmals bei Zimmertemperatur 7 g Lithiumaluminiumhydrid eingetragen und 8 Stunden das Reaktionsprodukt unter Rückfluß gehalten.To 134 g of α, α-diphenyl-y-dimethylarninovaleric acid and 2 l of tetrahydrofuran, 22 g of lithium aluminum trydride are carried at room temperature with stirring and heated the mixture to boiling for 15 hours. Then again at room temperature 7 g of lithium aluminum hydride entered and the reaction product under reflux for 8 hours held. Nach Zersetzen mit gesättigter Kochsalzlösung trennt man die flüssigen Anteile ab und befreit sie rom Lösungsmittel. Der Rückstand wird in verdünnter Salzsäure aufgenommen, mit Äther extrahiert md die abgetrennte wäßrig-saure Lösung mit Natronlauge alkalisiert. Das ausgeschiedene öl wird in &ther aufgenommen, die" vereinten Ätherauszüge leutral gewaschen und das Lösungsmittel abgeiampft. Die Destillation im Hochvakuum ergab 100 )is 108 g 2,2-Diphenyl-4-dimethylamino-pentanol-(l) rom Kp. 0,5 153 bis 162° C, das sind 78 bis 83% ler Theorie. Das Hydrochlorid hat einen Schmelzpunkt von 212 bis 214° C.After decomposition with saturated sodium chloride solution, the liquid components are separated off and freed from the solvent. The residue is taken up in dilute hydrochloric acid, extracted with ether, the separated aqueous acidic solution with sodium hydroxide solution md alkalized. The precipitated oil is taken up in ether, the combined ether extracts washed neutral and the solvent evaporated. The distillation in a high vacuum gave 100) is 108 g of 2,2-diphenyl-4-dimethylamino-pentanol- (1) rom bp 0.5 153 to 162 ° C, that is 78 to 83% of theory. The hydrochloride has a melting point of 212 to 214 ° C. RiRi pp [C)n-X[C) n -X R2 R 2 CH2OHCH 2 OH
Ar1 Ar 1 Ar9 Ar 9 worin Ar1 und Ar2 Phenylreste, gegebenenfalls substituierte Phenylreste sein können, die Alkylgruppe(Cn) eine geradlinige (R1=R2=H) oder verzweigte Kette (R1=H, R2= niedriger Alkylrest oder R1 und R2—niedriger Alkylrest) mit vorzugsweise 1 bis 4 Kohlenstoffatomen darstellt und der basische Substituent X, der seinen Sitz an einem der Arylkohlenwasserstoffe (Cn) hat, als primäres, sekundäres bzw. tertiäres oder cyclisches Amin vorliegt, dadurch gekennzeichnet, daß man die entsprechenden Carbonsäuren in einem hochsiedenden Lösungsmittel, vorzugsweise Tetrahydrofuran, bei Siedetemperatur unter mechanischer Rührung mit Lithiumaluminiumhydrid behandelt. ■, where Ar 1 and Ar 2 can be phenyl radicals, optionally substituted phenyl radicals, the alkyl group (Cn) is a straight (R 1 = R 2 = H) or branched chain (R 1 = H, R 2 = lower alkyl radical or R 1 and R 2 -Lower alkyl radical) with preferably 1 to 4 carbon atoms and the basic substituent X, which is located on one of the aryl hydrocarbons (C n ), is present as a primary, secondary or tertiary or cyclic amine, characterized in that the corresponding carboxylic acids treated in a high-boiling solvent, preferably tetrahydrofuran, at boiling point with mechanical stirring with lithium aluminum hydride. ■, Patentanspruch: in Betracht gezogene:Druckschriften:Claim: Considered: Publications: Verfahren zur Herstellung von primären ba- 25 Monatsh. Chem., 83, S. 541 bis 543 (1952), sischen Diarylalkoholen der allgemeinen Formel und 84 S. 1097 bis 1102 (1953).Process for the production of primary ba- 25 month h. Chem., 83, pp. 541 to 543 (1952), sischen diaryl alcohols of the general formula and 84 pp. 1097 to 1102 (1953). © 909 530/381 6.59© 909 530/381 6.59
DER19150A 1956-06-28 1956-06-28 Process for the preparation of primary basic diaryl alcohols Pending DE1059003B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DER19150A DE1059003B (en) 1956-06-28 1956-06-28 Process for the preparation of primary basic diaryl alcohols

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Application Number Priority Date Filing Date Title
DER19150A DE1059003B (en) 1956-06-28 1956-06-28 Process for the preparation of primary basic diaryl alcohols

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DE1059003B true DE1059003B (en) 1959-06-11

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2131885A1 (en) * 1971-04-01 1972-11-17 Ugine Kuhlmann

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2131885A1 (en) * 1971-04-01 1972-11-17 Ugine Kuhlmann

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