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DE1070186B - I Process for the production of antitussive 1,4-disubstituted piperazms - Google Patents

I Process for the production of antitussive 1,4-disubstituted piperazms

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Publication number
DE1070186B
DE1070186B DENDAT1070186D DE1070186DA DE1070186B DE 1070186 B DE1070186 B DE 1070186B DE NDAT1070186 D DENDAT1070186 D DE NDAT1070186D DE 1070186D A DE1070186D A DE 1070186DA DE 1070186 B DE1070186 B DE 1070186B
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DE
Germany
Prior art keywords
piperazine
melting point
hydroxyethyl
antitussive
dihydrochloride
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
DENDAT1070186D
Other languages
German (de)
Inventor
Morren Forest Brüssel Henri (Belgien)
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.)
Individual
Original Assignee
Individual
Publication date
Publication of DE1070186B publication Critical patent/DE1070186B/en
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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic 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
    • C07D295/04Heterocyclic 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
    • C07D295/10Heterocyclic 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 doubly bound oxygen or sulphur atoms
    • C07D295/104Heterocyclic 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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/108Heterocyclic 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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

DEUTSCHESGERMAN

kl. 12 ρ 6kl. 12 ρ 6

INTERNAT. KL. C 07INTERNAT. KL. C 07

PATENTAMTPATENT OFFICE

AUSLEGESCHRIFT 1070186EXPLAINING PUBLICATION 1070186

M37143IVb/12pM37143IVb / 12p

ANMELDETAG: 26.MÄRZ1958REGISTRATION DATE: MARCH 26, 1958

BEKANNTMACHUNG
DER ANMELDUNG
UND AUSGABE DER
AUSLEGESCHRIFT:
NOTICE
THE REGISTRATION
AND ISSUE OF THE
EDITORIAL:

3. DEZEMBER 1959DECEMBER 3, 1959

Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von hustenreizstillenden 1,4-disubstituierten Piperazinen der allgemeinen FormelThe invention relates to a method for Production of antitussive 1,4-disubstituted piperazines of the general formula

CO-CH9-CO-CH 9 -

— C .H-2- C .H-2

CH2-CHR''CH 2 -CHR ''

;n-rs ; no s

in der R und R1 ein Wasserstoffatom oder eine Hydroxylgruppe, R2 ein Wasserstoffatom oder eine Methylgruppe und R3 einen Alkylrest mit 1 bis 3 Kohlenstoffatomen, oder einen Cyclohexyl-, 2-Hydroxyäthyl-, 2-(2-Hydroxyäthoxy)-äthyl-, l,3-bis-(Diäthylamino)-isopropyl- und p-Chlorbenzhydrylrest darstellen, sowie deren salzsauren Salzen. .in which R and R 1 are a hydrogen atom or a hydroxyl group, R 2 is a hydrogen atom or a methyl group and R 3 is an alkyl radical with 1 to 3 carbon atoms, or a cyclohexyl, 2-hydroxyethyl, 2- (2-hydroxyethoxy) ethyl , represent l, 3-bis (diethylamino) isopropyl and p-chlorobenzhydryl radicals, as well as their hydrochloric acid salts. .

Diese verfahrensgemäß hergestellten Stoffe besitzen eine beträchtliche hustenreizstillende Wirkung, welche 150°/0 derjenigen des Codeins bei gleicher Dosierung überschreiten kann. Besonders wirksam sind diejenigen Derivate, bei welchen R, R1 These substances produced according to the method have a significant antitussive relieving effect, which can be 150 ° / 0 that of codeine at the same dosage exceed. Those derivatives in which R, R 1

R2 und R3 R 2 and R 3

der erwähntenthe mentioned

allgemeinen Formel folgende Bedeutung haben:general formula have the following meaning:

R = Wasserstoff, R1= Wasserstoff, R2= Wasserstoff, R3= 2-Hydroxyäthyl; R = Hydroxyl, R1= Hydroxyl, R2= Wasserstoff, R3= 2-Hydroxyäthyl.R = hydrogen, R 1 = hydrogen, R 2 = hydrogen, R 3 = 2-hydroxyethyl; R = hydroxyl, R 1 = hydroxyl, R 2 = hydrogen, R 3 = 2-hydroxyethyl.

Die hustenreizstillende Wirkung dieser Stoffe war völlig unvorhersehbar.The cough-relieving effect of these substances was completely unpredictable.

Diese Produkte sind vom pharmakologischen Standpunkt deshalb von Interesse, weil sie nur eine sehr schwache Giftigkeit aufweisen.These products are of interest from a pharmacological point of view because they are only one very show weak toxicity.

Die Verfahrensprodukte können nach den klassischen Synthesemethoden erhalten werden. So können sie hergestellt werden, indem man eina-Chlor-S-R-4-Rj-acetophenon, substituiert oder nicht, mit einem 1-R3-Piperazin nachThe process products can be obtained by the classical synthesis methods. So they can be prepared by substituting an α-chloro-SR-4-Rj-acetophenone, or not, with a 1-R 3 -piperazine

Verfahren zur HerstellungMethod of manufacture

von hustenreizstillendenof cough suppressants

1,4-disubstituierten Piperazinen1,4-disubstituted piperazines

Anmelder:
Henri Morren, Forest, Brüssel (Belgien)
Applicant:
Henri Morren, Forest, Brussels (Belgium)

Vertreter: Dr.-Ing. A. van der Werth, Patentanwalt,
Hamburg-Harburg 1, Wilstorfer Str. 32
Representative: Dr.-Ing. A. van der Werth, patent attorney,
Hamburg-Harburg 1, Wilstorfer Str. 32

Beanspruchte Priorität:
Belgien vom 29. März 1957 und 21. Januar 1958
Claimed priority:
Belgium of March 29, 1957 and January 21, 1958

Henri Morren, Forest, Brüssel (Belgien),
ist als Erfinder genannt worden
Henri Morren, Forest, Brussels (Belgium),
has been named as the inventor

Beispiel 1
l-Phenacyl-4-methylpiperazin-dihydrochlorid
example 1
1-phenacyl-4-methylpiperazine dihydrochloride

Man erwärmt am Rückfluß während 3 Stunden eine Lösung von 0,1 Mol 1-Methylpiperazin mit 0,1 Mol Phenacylchlorid in 200 ecm Aceton. Man kühlt in einem Eisbad und nitriert die gebildeten Kristalle. Man löst sie in 60 ecm siedendem Äthanol, nitriert über Aktivkohle und gibt einen leichten Überschuß von Salzsäure in alkoholischer Lösung hinzu. Das entsprechende Dihydrochlorid kristallisiert aus. Man erhält 13 g Dihydrochlorid des 1 -Phenacyl-4-methyrpiperazms. Schmelzpunkt 228° C.A solution of 0.1 mol of 1-methylpiperazine with 0.1 mol is heated under reflux for 3 hours Phenacyl chloride in 200 ecm acetone. It is cooled in an ice bath and the crystals formed are nitrated. One solves it in 60 ecm boiling ethanol, nitrated over activated charcoal and gives a slight excess of hydrochloric acid in alcoholic solution. The corresponding dihydrochloride crystallizes out. 13 g of dihydrochloride are obtained des 1-phenacyl-4-methyrpiperazms. Melting point 228 ° C.

Beispiel 2Example 2

CO-CH9ClCO-CH 9 Cl

HNHN

4040

/ CHR2— CH2n / CHR 2 - CH 2n

CH2—CHR2 CH 2 -CHR 2

,CHRn-CH8 , CHRn-CH 8

XH9-CHR9 XH 9 -CHR 9

l-PhenacyM-isopropylpiperazin-hydfochloridl-PhenacyM-isopropylpiperazine hydrofochloride

Man erwärmt eine Lösung von 0,07 Mol 1-Isopropylpiperazin und 0,07 Mol Phenacylchlorid in 150 ecm Aceton 2 Stunden am Rückfluß. Nach dem Abkühlen filtriert man die gebildeten Kristalle ab und kristallisiert sie aus 100 ecm siedendem Äthanol um. Man erhält 9,5 g 1 - Phenacyl - 4 - isopropylpiperazin - hydrochlorid vom Schmelzpunkt 178° C.A solution of 0.07 mol of 1-isopropylpiperazine is heated and 0.07 moles of phenacyl chloride in 150 ecm of acetone 2 hours at reflux. After cooling, the crystals formed are filtered off and crystallized from 100 ecm boiling ethanol. 9.5 g are obtained 1 - Phenacyl - 4 - isopropylpiperazine hydrochloride with a melting point of 178 ° C.

;n-r3 50; nr 3 50

umsetzt.implements.

Beispiel 3Example 3

l-Phenacyl^-n-propylpiperazin-hydrochloridl-phenacyl ^ -n-propylpiperazine hydrochloride

Diese Verbindung wird gemäß Beispiel 2 hergestellt und schmilzt, aus einer Mischung Äthanol—Äther umkristallisiert, bei 125° C.This compound is prepared according to Example 2 and melts from a mixture of ethanol and ether recrystallized, at 125 ° C.

Beispiel 4 ' 1>: ■<■ " ■ .... ;■ '■·■ c'' Example 4 '1>: ■ <■ "■ ....; ■' ■ · ■ c ''

1 -Phenacyl-4- (2-hydroxyäthyl) -piperazin-dihydrochlorid1-phenacyl-4- (2-hydroxyethyl) piperazine dihydrochloride

Man geht von l-(2-Hydroxy^thyl)-piperazin aus und arbeitet, wie im Beispiel 1 beschrieben. Schmelzpunkt: 5'■' 24O0C.One starts from l- (2-Hydroxy ^ thyl) piperazine and works as described in Example 1. Melting point: 5 '■' 24O 0 C.

: Beispiel 5 : Example 5

. 1 -Phenacyl-4- [2-(2-hydroxyäthoxy) -äthyl] piperazin-dihydrochlorid . 1-phenacyl-4- [2- (2-hydroxyethoxy) ethyl] piperazine dihydrochloride

Man erwärmt ein Gemsich aus 0,5 Mol l-[2-(2-Hydroxyäthoxy)-äthyl]-piperazin, 0,6MoI Triäthylamin und 0,5 Mol Phenacylchlorid in 500 ecm Toluol 4 Stunden am Rückfluß. Nach dem Abkühlen filtriert man das gebildete Triäthylaminchlorhydrat ab und dampft das Filtrat unter Vakuum ein. Der hierbei erhaltene Rückstand wird in siedendem Äthanol gelöst und über Aktivkohle filtriert. Nun setzt man zur Lösung einen leichten Überschuß Salzsäure in alkoholischer Lösung zu, um das entspre- · chende Dihydrochlörid zu bilden. Man läßt kristallisieren und erhält 154 g 1-Phenacyl-4-[2-(2-hydroxyäthoxy)-äthyl]-piperazinhydrochlorid vom Schmelzpunkt 205° C.A mixture of 0.5 mol of 1- [2- (2-hydroxyethoxy) ethyl] piperazine is heated, 0.6 mol of triethylamine and 0.5 mol of phenacyl chloride in 500 ecm of toluene for 4 hours Reflux. After cooling, the triethylamine chlorohydrate formed is filtered off and the filtrate is evaporated under vacuum. The residue obtained in this way is dissolved in boiling ethanol and filtered through activated charcoal. A slight excess of hydrochloric acid in alcoholic solution is now added to the solution in order to corresponding dihydrochloride to form. It is allowed to crystallize and 154 g of 1-phenacyl-4- [2- (2-hydroxyethoxy) ethyl] piperazine hydrochloride are obtained with a melting point of 205 ° C.

BeispieloExample

1 - (3,4-Dihydroxyphenacyl) -4- (2-hydroxyäthyl) piperazin-dihydrochlorid 1 - (3,4-Dihydroxyphenacyl) -4- (2-hydroxyethyl) piperazine dihydrochloride

Man löst 0,5 Mol a-Chlor-S^-dihydroxyacetophenon in 500 ecm wasserfreiem Aceton, setzt unter mechanischem Rühren 0,5 Mol l-(2-Hydroxyäthyl)-piperazin zu und erwärmt das Gemisch 2 Stunden am Rückfluß. Es bildet sich ein Öl, welches noch während der Umsetzung kristallisiert. Hierauf dekantiert man das Aceton ab, nimmt den Rückstand in Wasser auf und säuert mit Salzsäure an. Die Lösung wird über Tierkohle filtriert und dann konzentriert, wobei das 1-(3,4-Dihydroxyphenacyl) - 4 - (2 - hydroxyäthyl) - piperazin - dihydrochlörid bei Zusatz von Alkohol auskristallisiert. Man kristallisiert das Salz in einem Gemisch aus Wasser—Alkohol um. Das mit einer Ausbeute von 75°/0 erhaltene Dihydrochlörid enthält 2 Mol Kristallwasser und hat einen Schmelzpunkt von 195° C.0.5 mol of α-chloro-S ^ -dihydroxyacetophenone is dissolved in 500 ecm of anhydrous acetone, 0.5 mol of 1- (2-hydroxyethyl) piperazine is added with mechanical stirring and the mixture is refluxed for 2 hours. An oil is formed which crystallizes during the reaction. The acetone is then decanted off, the residue is taken up in water and acidified with hydrochloric acid. The solution is filtered through animal charcoal and then concentrated, the 1- (3,4-dihydroxyphenacyl) -4 - (2-hydroxyethyl) piperazine dihydrochloride crystallizing out when alcohol is added. The salt is recrystallized from a mixture of water and alcohol. The dihydrochloride obtained with a yield of 75 ° / 0 contains 2 moles of water of crystallization and has a melting point of 195 ° C.

Beispiel 7Example 7

1 - (4-Hydroxyphenacyl) -4- [2- (2-hydroxyäthoxy) -äthyl].- ' piperazin-monohydrochlorid .1 - (4-Hydroxyphenacyl) -4- [2- (2-hydroxyethoxy) ethyl] .- ' piperazine monohydrochloride.

Zu einer Lösung von 0,15 Mol a-Chlor-4-hydroxyacetophenon in 100 ecm siedendem Aceton fügt man allmählich eine Lösung von 0,15 Mol l-[2-(2-Hydroxyäthoxy)-äthyl]-piperazin in 50 ecm wasserfreiem Aceton zu und erwärmt 6 Stunden am Rückfluß. Dann filtriert man die gebildeten Kristalle ab und kristallisiert sie aus Alkohol um. Man erhält in einer Ausbeute von 70% das Monohydrochlorid des 1 - (4-Hydroxyphenacyl)-4-[2-(2-hydroxyäthoxy)-äthyl]-piperazins vom Schmelzpunkt 1060C.A solution of 0.15 mol of 1- [2- (2-hydroxyethoxy) ethyl] piperazine in 50 ecm of anhydrous acetone is gradually added to a solution of 0.15 mol of α-chloro-4-hydroxyacetophenone in 100 ecm of boiling acetone and heated to reflux for 6 hours. The crystals formed are then filtered off and recrystallized from alcohol. In a yield of 70%, to yield the monohydrochloride of 1 - (4-hydroxyphenacyl) -4- [2- (2-hydroxyethoxy) -ethyl] -piperazine having a melting point of 106 0 C.

Die nachstehenden Verbindungen werden nach dem in den Beispielen 6 und 7 beschriebenen Verfahren durch 2- bis ostündiges Erhitzen hergestellt. ' ! The following compounds are prepared according to the procedure described in Examples 6 and 7 by heating for 2 to 3 hours. ' !

■ 1 - (4-Hydroxyphenacyl) -4-(2-hydroxyä.thyl) -piperazinmonohydrochlorid. Schmelzpunkt 160° C. \.l (4-Hydroxyphenacyl) -2,5-dimethyl-4- (2-hydroxyäthyl)-piperazin-dihydrochlorid. Schmelzpunkt 228 bis 230° C. :■ 1 - (4-Hydroxyphenacyl) -4- (2-hydroxyethyl) piperazine monohydrochloride. Melting point 160 ° C. 1. (4-Hydroxyphenacyl) -2,5-dimethyl-4- (2-hydroxyethyl) piperazine dihydrochloride. Melting point 228 to 230 ° C.:

- (3,4 - Dihydroxyphenacyl) - 4 - methylpiperazin - dihydrochlörid. Schmelzpunkt 241 bis 243° C.- (3,4 - Dihydroxyphenacyl) - 4 - methylpiperazine - dihydrochloride. Melting point 241 to 243 ° C.

- (3,4 - Dihydroxyphenacyl) - 4 - isopropylpiperazinmonohydrochlorid. Schmelzpunkt 180° C.- (3,4 - Dihydroxyphenacyl) - 4 - isopropylpiperazine monohydrochloride. Melting point 180 ° C.

- (3,4 - Dihydroxyphenacyl) - 4 - cyclohexylpiperazinmonohydrochlorid. Schmelzpunkt 215 bis 217° C.- (3,4 - Dihydroxyphenacyl) - 4 - cyclohexylpiperazine monohydrochloride. Melting point 215 to 217 ° C.

l-(3,4-Dihydroxyphenacyl)-2,5-dimethyl-4-(2-hydroxyäthyl)-piperazin-dihydrochlorid. Schmelzpunkt 226 bis 228° C.1- (3,4-Dihydroxyphenacyl) -2,5-dimethyl-4- (2-hydroxyethyl) piperazine dihydrochloride. Melting point 226 to 228 ° C.

- (3,4-Dihydroxyphenacyl) -4- (p-Chlorbenzhydryl)-piperazin-dihydrochlorid. Schmelzpunkt 185° C.- (3,4-Dihydroxyphenacyl) -4- (p-chlorobenzhydryl) -piperazine dihydrochloride. Melting point 185 ° C.

- (3,4-Dihydroxyphenacyl) -4- [2- (2-hydroxyäthoxy)-äthyl]-piperazin-dihydrochlorid. - (3,4-Dihydroxyphenacyl) -4- [2- (2-hydroxyethoxy) ethyl] piperazine dihydrochloride.

Dieses Dihydrochlörid der allgemeinen Formel C16 H24 O6 N2 · 2 H Cl besitzt keinen scharf en Schmelzpunkt. Die Analyse hat folgende Werte ergeben:This dihydrochloride of the general formula C 16 H 24 O 6 N 2 · 2 H Cl does not have a sharp melting point. The analysis showed the following values:

Berechnet N 7,05%, Cl 17,88%;Calculated N 7.05%, Cl 17.88%;

gefunden N 7,02%, Cl 18,0%.found N 7.02%, Cl 18.0%.

1 - (3,4 - Dihydroxyphenacyl)- 4- [1,3- bis- (diäthylamino)-isopropyl]-piperazin-tetrahydrochlorid. 1 - (3,4 - Dihydroxyphenacyl) - 4- [1,3- bis (diethylamino) isopropyl] piperazine tetrahydrochloride.

Das Tetrahydrochlorid dieser Verbindung der allgemeinen Formel C23H40O3N4-4HCl besitzt keinen scharfen Schmelzpunkt. Die Analyse hat folgende Werte ergeben:The tetrahydrochloride of this compound of the general formula C 23 H 40 O 3 N 4 -4HCl does not have a sharp melting point. The analysis showed the following values:

Berechnet N 9,90%, Cl 25,1 %;Calculated N 9.90%, Cl 25.1%;

gefunden ....... N 9,81 %, Cl 25,3%.found ....... N 9.81%, Cl 25.3%.

Zur Herstellung der Verfahrensprodukte wurden als Ausgangsstoffe 1 -(2-Hydroxyäthyl)-2,5-dimethyl-piperazin, 1 - [2 - (2 - Hydroxyäthoxy)-äthyl] - piperazin und 1-[1,3-bis-(Diäthylamino)-isopropyl]-pipefazin verwendet, die nach an sich bekannten Verfahren hergestellt werden können. ■■·.;>.·For the preparation of the process products 1 - (2-hydroxyethyl) -2,5-dimethyl-piperazine were used as starting materials, 1 - [2 - (2 - Hydroxyäthoxy) -äthyl] - piperazine and 1- [1,3-bis- (diethylamino) -isopropyl] -pipefazin used, which can be prepared by processes known per se. ■■ ·.;>. ·

Die Siedepunkte der genannten Ausgangsstoffe liegen (ihrer Reihenfolge nach) bei 126 bis 127° C (12 mm); bis 132° C (0,7 mm) und 163 bis 165° C (12 mm).The boiling points of the starting materials mentioned are (according to their sequence) from 126 to 127 ° C (12 mm); up to 132 ° C (0.7 mm) and 163 to 165 ° C (12 mm).

Auf die Herstellung dieser Stoffe wird kein Schutzbegehren gerichtet.No protection request is made for the manufacture of these substances.

Claims (1)

Patentanspruch:Claim: Verfahren zur Herstellung von hustenreizstillend wirkenden 1,4-disubstituierten Piperazinen der allgemeinen FormelProcess for the preparation of antitussive 1,4-disubstituted piperazines of the general formula CHRo-CHCHRo-CH 2\ 2 \ in der R und R1
Hydroxylgruppe, R2
in the R and R 1
Hydroxyl group, R 2
>-CO-CH2-N(> -CO-CH 2 -N ( ein
ein
a
a
C Ho— C H R9 C Ho - CHR 9 Wasserstoffatom oder eine Wasserstoffatom oder eine Methylgruppe und R3 einen Alkylrest mit 1 bis 3 Kohlenstoffatomen oder einen Cyclohexyl-, 2-Hydroxyäthyl-, 2-(2-Hydroxyäthoxy)-äthyl-, l,3-bis-(Diäthylamino)-isopropyl- und p-Chlorbenzhydrylrest darstellt, sowie deren salzsauren Salzen, dadurch gekennzeichnet, daß man ein definitionsgemäß substituiertes a-Chloracetophenon mit einem 1-R3-Piperazin umsetzt.Hydrogen atom or a hydrogen atom or a methyl group and R 3 is an alkyl radical with 1 to 3 carbon atoms or a cyclohexyl, 2-hydroxyethyl, 2- (2-hydroxyethoxy) ethyl, 1,3-bis (diethylamino) isopropyl and represents p-chlorobenzhydryl radical, and their hydrochloric acid salts, characterized in that an α-chloroacetophenone which is substituted by definition is reacted with a 1-R 3 -piperazine. © 909 687/400 11.59© 909 687/400 11:59
DENDAT1070186D I Process for the production of antitussive 1,4-disubstituted piperazms Pending DE1070186B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1093368B (en) 1958-01-21 1960-11-24 Henri Morren Process for the preparation of piperazine derivatives

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1093368B (en) 1958-01-21 1960-11-24 Henri Morren Process for the preparation of piperazine derivatives

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