DE1570013C - 1,4 Bis (phenoxyacetyi) piperazinden vate and process for their preparation - Google Patents
1,4 Bis (phenoxyacetyi) piperazinden vate and process for their preparationInfo
- Publication number
- DE1570013C DE1570013C DE1570013C DE 1570013 C DE1570013 C DE 1570013C DE 1570013 C DE1570013 C DE 1570013C
- Authority
- DE
- Germany
- Prior art keywords
- bis
- piperazine
- general formula
- preparation
- phenoxyacetyl
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- CDQDCIXXBFSRJQ-UHFFFAOYSA-N 2-phenoxy-1-[4-(2-phenoxyacetyl)piperazin-1-yl]ethanone Chemical class C1CN(C(=O)COC=2C=CC=CC=2)CCN1C(=O)COC1=CC=CC=C1 CDQDCIXXBFSRJQ-UHFFFAOYSA-N 0.000 claims description 6
- YFVKHKCZBSGZPE-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(propylamino)propan-1-one Chemical compound CCCNC(C)C(=O)C1=CC=C2OCOC2=C1 YFVKHKCZBSGZPE-UHFFFAOYSA-N 0.000 claims description 2
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005179 haloacetyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 2
- 229960002510 mandelic acid Drugs 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940031826 phenolate Drugs 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- -1 3-methoxyphenoxy Chemical group 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QYHXZQGNMLVJPX-UHFFFAOYSA-N 2-chloro-1-[4-(2-chloroacetyl)piperazin-1-yl]ethanone Chemical compound ClCC(=O)N1CCN(C(=O)CCl)CC1 QYHXZQGNMLVJPX-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229960005141 piperazine Drugs 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960003506 piperazine hexahydrate Drugs 0.000 description 2
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- UGRMITBWUVWUEB-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-3-methylbenzene Chemical group CC1=CC=CC([O])=C1 UGRMITBWUVWUEB-UHFFFAOYSA-N 0.000 description 1
- RQYIJSLZUGNKGP-UHFFFAOYSA-N 2-(2-methylphenoxy)-1-[4-[2-(2-methylphenoxy)acetyl]piperazin-1-yl]ethanone Chemical compound CC1=CC=CC=C1OCC(=O)N1CCN(C(=O)COC=2C(=CC=CC=2)C)CC1 RQYIJSLZUGNKGP-UHFFFAOYSA-N 0.000 description 1
- ZFNHZAHQXYCCTJ-UHFFFAOYSA-N 2-(4-methoxyphenoxy)-1-[4-[2-(4-methoxyphenoxy)acetyl]piperazin-1-yl]ethanone Chemical compound C1=CC(OC)=CC=C1OCC(=O)N1CCN(C(=O)COC=2C=CC(OC)=CC=2)CC1 ZFNHZAHQXYCCTJ-UHFFFAOYSA-N 0.000 description 1
- VQDQZTLOPJNUCD-UHFFFAOYSA-N 2-(4-methylphenoxy)-1-[4-[2-(4-methylphenoxy)acetyl]piperazin-1-yl]ethanone Chemical compound C1=CC(C)=CC=C1OCC(=O)N1CCN(C(=O)COC=2C=CC(C)=CC=2)CC1 VQDQZTLOPJNUCD-UHFFFAOYSA-N 0.000 description 1
- PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 description 1
- KLSLBUSXWBJMEC-UHFFFAOYSA-N 4-Propylphenol Chemical compound CCCC1=CC=C(O)C=C1 KLSLBUSXWBJMEC-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
Description
1 21 2
Die Erfindung betrifft neue l,4-Bis-(phenoxyacetyl)-piperazinderivate der allgemeinen FormelThe invention relates to new 1,4-bis (phenoxyacetyl) piperazine derivatives of the general formula
/CH2 CH2v/ CH 2 CH 2 v
0-CH2-CO-N N-CO-CH2-OO-CH 2 -CO-N N-CO-CH 2 -O
^CH2-CH2/^ CH 2 -CH 2 /
in der R ein Wasserstoffatom, einen Methyl- oder Propylrest oder einen in m- oder p-Stellung stehenden Methoxyrest bedeutet, und Verfahren zu ihrer Herstellung. Die neuen l,4-Bis-(phenoxyacetyl)-piperazinderivate der allgemeinen Formel I werden dadurch hergestellt, daß man in an sich bekannter Weise entwederin which R is a hydrogen atom, a methyl or propyl radical or one in the m- or p-position Means methoxy radical and process for their preparation. The new 1,4-bis (phenoxyacetyl) piperazine derivatives of the general formula I are prepared by in a manner known per se either
a) ein l,4-Bis-(halogenacetyl)-piperazin der allgemeinen Formela) a 1,4-bis (haloacetyl) piperazine of the general formula
/CH2- CH2^/ CH 2 - CH 2 ^
HaI-CH2-CO-N N-CO-CH2-HaIHal-CH 2 -CO-N N-CO-CH 2 -HaI
XCH2 — CH/ X CH 2 - CH /
worin Hai ein Halogenatom bedeutet, mit einem Phenolat der allgemeinen Formelwherein Hai denotes a halogen atom, with a phenolate of the general formula
worin Me ein Alkalimetallatom bedeutet, umsetzt oder b) Piperazin mit einem Halogenid, Anhydrid oder Alkylester einer Phenylglykolsäure der allgemeinen Formelin which Me is an alkali metal atom, or b) reacts piperazine with a halide, anhydride or alkyl ester of a phenylglycolic acid of the general formula
Y V- O — CH2 — COOHY V-O-CH 2 -COOH
umsetzt.implements.
Die Verfahrensweise b) wird in Gegenwart von Aceton oder einem aromatischen Kohlenwasserstoff als Lösungsmittel durchgeführt.Procedure b) is carried out in the presence of acetone or an aromatic hydrocarbon carried out as a solvent.
Die Piperazinderivate der allgemeinen Formel I besitzen wertvolle pharmakologische Eigenschaften, da sie depressiv auf das Zentralnervensystem, analgetisch und hustenstillend· wirken.The piperazine derivatives of general formula I have valuable pharmacological properties, because they have a depressive effect on the central nervous system, have an analgesic and cough suppressant effect.
Die analgetische Wirkung; einiger der Verbindungen gemäß der Erfindung wurde nach der Druckmethode an Mäuseschwänzen bestimmt.The analgesic effect; some of the connections according to the invention was determined by the pressure method on mouse tails.
Gemäß der Druckmethode wird auf die Schwanzgelenke der Mäuse (Körpergewicht.je 20 bis 25 g) ein Druck ausgeübt, dessen Höhe mittels eines Kymographen registriert wird, sobald die Versuchstiere infolge des durch den Druck verursachten Schmerzes Fluchtreaktionen zeigen. Der Schwanzdruck wird sechsmal in Zeitabsländen von je 20 Minuten nach der intraperitonealen Verabfolgung der zu f>5 prüfenden Verbindungen ausgeübt.According to the pressure method, the tail joints of the mice (body weight: 20 to 25 g each) a pressure is exerted, the level of which is recorded by means of a kymograph, as soon as the test animals show escape reactions as a result of the pain caused by the pressure. The tail print becomes f> 5 six times at 20-minute intervals after intraperitoneal administration of the f> 5 testing connections exercised.
Als Vergleichssubstanz wurde Natrium-l-phenyl-2,3 - dimethyl - 5 - pyrazolon - 4 - methylaminomethansulfonat verwendet. Die zu prüfenden Verbindungen wurden an Gruppen von je 10 Mäusen intraperitoneal verabreicht, und zwar jede Substanz in zwei verschiedenen Dosen: die Vergleichssubstanz in Dosen von 300 und 400 mg/kg und die erfindungsgemäßen Verbindungen in Dosen im Bereich von 50 bis KK) mg/kg. Bei den Versuchstieren wurde die Reaktion als Schwellenwert bestimmt. Die Ergebnisse für die Wirksamkeit der Verbindungen wurden nach der Methode von J. H. Burn, D.J. Finney und L. G. Goodwin (vgl. Biological Standardization, 2. Auflage, Verlag Oxford University Press, 1950) und von D. J. Finney (vgl. Statistical Methods in Biological Assay, Verlag C. Griffin, 1952) berechnet.Sodium-1-phenyl-2,3 was used as a comparison substance - dimethyl - 5 - pyrazolone - 4 - methylaminomethanesulfonate is used. The connections to be tested were administered intraperitoneally to groups of 10 mice each, each substance in two different Doses: the comparison substance in doses of 300 and 400 mg / kg and the compounds according to the invention in doses ranging from 50 to KK) mg / kg. In the test animals, the reaction was as Threshold determined. The results for the effectiveness of the compounds were after Method of J. H. Burn, D.J. Finney and L. G. Goodwin (see Biological Standardization, 2nd edition, Verlag Oxford University Press, 1950) and by D. J. Finney (cf. Statistical Methods in Biological Assay, Verlag C. Griffin, 1952).
Die LDjo-Werte betragen bei intraperitonealer Verabreichung an Mäuse für die Vergleichssubstanz 1620 mg/kg und für die Verbindungen gemäß der Erfindung > 1000 mg/kg.The LDjo values are intraperitoneally Administration to mice for the comparison substance 1620 mg / kg and for the compounds according to FIG Invention> 1000 mg / kg.
Die bei der Prüfung auf analgetische Wirksamkeit erhaltenen Ergebnisse finden sich in der folgenden Tabelle.The results obtained in testing for analgesic effectiveness are shown below Table.
N-CO-CH2-O-^N-CO-CH 2 -O- ^
V- O — CH2 — CO — NV - O - CH 2 - CO - N
Wirksamkeit nach der Druckmethode,Effectiveness according to the printing method,
bezogen auf Natrium-l-phenyl-based on sodium-l-phenyl-
2,.Vdimethyl-2, .Vdimethyl-
S-pyrazolon-4-methyl-S-pyrazolone-4-methyl-
aminomethan-aminomethane
sulfonat = Isulfonate = I.
OCH3
/ V-O-CH2-CO-OCH 3
/ VO-CH 2 -CO-
— CO — CH — O —/)- CO - CH - O - /)
CO — CH2 —CO - CH 2 -
0-CH2-CO-N N-CO-CH2-OO-CH 2 -CO-N N-CO-CH 2 -O
N — CO — CH2-N - CO - CH 2 -
—CH2-CO-CH 2 -CO
O — CH2 — CO — N N-CO-CH2-O —# O - CH 2 - CO - N N-CO-CH 2 -O - #
— CO-CH2-O-/- CO-CH 2 -O- /
C3HC 3 H
/ V-O-CH2-CO-5,897 / VO-CH 2 -CO-5,897
5,260 7,5995,260 7,599
5,265.26
5,88 4,62 7,6875.88 4.62 7.687
4545
Zur Erläuterung der Herstellungsweise der Verbin- Analyse für C22H26O6N2: düngen gemäß der Erfindung dienen die folgenden 4o Bercchnet c ö>75i H 6,32, N 6,76%; BeisP'elc: gefunden .... C 63,79, H 6,06, N 6,72%.To explain the method of preparation of the compound analysis for C 22 H 26 O 6 N 2 : fertilize according to the invention, the following 4 o Calculations c ö> 75i H 6.32, N 6.76%; At P ' elc: found .... C 63.79, H 6.06, N 6.72%.
Beispiel 1
l,4-Bis-(phenoxyacetyl)-piperazinexample 1
1,4-bis (phenoxyacetyl) piperazine
1,15 g Natrium werden in 150 ml Äthanol gelöst. Die Lösung wird mit 4,71 g Phenol und dann mit 5,98 g l,4-Bis-(chloracetyl)-piperazin gemischt. Das Gemisch wird unter Rühren erhitzt, bis es neutral reagiert. Nach beendeter Umsetzung wird der kristalline Stoff abfiltriert und mit Wasser gewaschen. Nach dem Umkristallisieren aus Dimethylformamid erhält man 6,3 g Endprodukt; Ausbeute: 71,1%; F. 203 bis 204° C.1.15 g of sodium are dissolved in 150 ml of ethanol. The solution is made with 4.71 g of phenol and then with 5.98 g 1,4-bis (chloroacetyl) piperazine mixed. The mixture is heated with stirring until neutral reacted. When the reaction has ended, the crystalline substance is filtered off and washed with water. To Recrystallization from dimethylformamide gives 6.3 g of the end product; Yield: 71.1%; F. 203 to 204 ° C.
Analyse für C20H22O4N2:Analysis for C 20 H 22 O 4 N 2 :
Berechnet ... C 67,78, H 6,26, N 7,90%;
gefunden .... C 67,87, H 6,39, N 7,87%.Calculated ... C 67.78, H 6.26, N 7.90%;
found .... C 67.87, H 6.39, N 7.87%.
Beispiel 2
l,4-Bis-[(3-methoxyphenoxy)-acctyl]-pipcrazin Beispiel 3
l,4-Bis-[(4-methoxyphenoxy)-acetyl]-piperazinExample 2
1,4-Bis - [(3-methoxyphenoxy) -acctyl] -pipcrazine Example 3 1,4-Bis - [(4-methoxyphenoxy) -acetyl] -piperazine
Nach dem Verfahren der vorhergehenden Beispiele erhält man aus 1,67 g Natrium, 300 ml Äthanol, 9 g Hydrochinonmonomethyläther und 8,68 g 1,4-Bis-(chloracetyl)-piperazin nach dem Umkristallisieren aus Dioxan 14,8 g der obengenannten Verbindung; Ausbeute: 71,5%; F. 168 bis 169°C.Following the procedure of the preceding examples, 1.67 g of sodium, 300 ml of ethanol, 9 g of hydroquinone monomethyl ether and 8.68 g of 1,4-bis (chloroacetyl) piperazine after recrystallization from dioxane, 14.8 g of the abovementioned compound; Yield: 71.5%; M.p. 168 to 169 ° C.
Analyse Tür C22H26O6N2:Analysis door C 22 H 26 O 6 N 2 :
Bercchnet ... C 63,75, H 6,32, N 6,76%; gefunden .... C 63,53, H 6,44, N 6,96%.Calculated ... C 63.75, H 6.32, N 6.76%; found .... C 63.53, H 6.44, N 6.96%.
Be i s pie I 4Be i s pie I 4
l,4-Bis-[(2-mcthylphenoxy)-acetyl]-piperazin1,4-Bis - [(2-methylphenoxy) acetyl] piperazine
Nach dem Verfahren von Beispiel 1 erhält man aus Nach dem Verfahren der obigen Beispiele erhältFollowing the procedure of Example 1 gives: Following the procedure of the above examples
2,3 g Natrium, 200 ml Äthanol, 12,4 g Resorcinmono- man aus 2,3 g Natrium, 200 ml Äthanol, 10,8 g
methyläther und 11,95 g l,4-Bis-(chloracetyl)-piper- 6S o-Kresol und 11,95 g l,4-Bis-(chloracetyI)-piperazin
äzin nach dem Umkristallisieren aus Äthanol 12,6 g
der obengenannten Verbindung; Ausbeute: 60,8%;2.3 g of sodium, 200 ml of ethanol, 12.4 g of resorcinol mono- man from 2.3 g of sodium, 200 ml of ethanol, 10.8 g of methyl ether and 11.95 g of 4-bis (chloroacetyl) piper- 6 S o-cresol and 11.95 g of 4-bis (chloroacetyI) piperazine azine after recrystallization from ethanol 12.6 g
the above compound; Yield: 60.8%;
F. 153 bis 154" C.F. 153 to 154 "C.
nach dem Umkristallisieren aus Chloroform und Äthanol 12,8 g der obengenannten Verbindung; Ausbeute: 67%; F. 171 bis 173"C.after recrystallization from chloroform and ethanol, 12.8 g of the above-mentioned compound; Yield: 67%; F. 171 to 173 "C.
Analyse für C22H20O4N2:Analysis for C 22 H 20 O 4 N 2 :
Berechnet ... C 69,09, H 6,85, N 7,33%; gefunden .... C 69,30, H 6,85, N 7,36%.Calculated ... C 69.09, H 6.85, N 7.33%; found .... C 69.30, H 6.85, N 7.36%.
Beispiel 5 l,4-Bis-[(3-mcthylphenoxy)-acetyl]-pipcrazinExample 5 1,4-Bis - [(3-methylphenoxy) acetyl] pipcrazine
Verwendet man bei dem Verfahren des Beispiels 4 m-Kresol an Stelle des o-Kresols, so erhält man das obengenannte Produkt in einer Ausbeute von 13,7 g (71,6%); F. 140 bis 142 C. .If 4 m-cresol is used in place of the o-cresol in the process of the example, this is obtained above product in a yield of 13.7 g (71.6%); F. 140 to 142 C..
Analyse für C22H211O4N2:Analysis for C 22 H 211 O 4 N 2 :
Berechnet ... C 69,09, H 6,85, N 7,33"/,,: '5Calculated ... C 69.09, H 6.85, N 7.33 "/ ,,: '5
gefunden .... C 69,27, H 6,80, N 7,17%.found .... C 69.27, H 6.80, N 7.17%.
Beispiel 7 1.4-Bis-[(4-propylphenoxy)-acetyl]-piperazinExample 7 1,4-bis - [(4-propylphenoxy) acetyl] piperazine
10 g (0,0586 Mol) Phenoxyacetylchlorid zu der mit Eis auf 8 bis 10° C gekühlten Lösung unter Rühren bilden sich weiße Kristalle. Die Kristalle werden gründlich nacheinander mit 200 ml 10%igcr Salzsäure, 200 ml 10%iger Natronlauge und schließlich mit Wasser gewaschen. Durch Umkristallisieren aus Dimethylformamid erhält man das Endprodukt in einer Ausbeute von 7,3 g (70,2%); F. 205 C.Add 10 g (0.0586 mol) of phenoxyacetyl chloride to the solution, which has been cooled to 8 to 10 ° C. with ice, while stirring white crystals form. The crystals are thoroughly washed one after the other with 200 ml of 10% hydrochloric acid, 200 ml of 10% sodium hydroxide solution and finally washed with water. By recrystallization Dimethylformamide is obtained in the end product in a yield of 7.3 g (70.2%); F. 205 C.
Analyse für C20H22O4N2:Analysis for C 20 H 22 O 4 N 2 :
Berechnet ... C 67,78, H 6,26, N 7,90%:
gefunden .... C 67,97, H 6,39, N 7,87%.Calculated ... C 67.78, H 6.26, N 7.90%:
found .... C 67.97, H 6.39, N 7.87%.
Beispiel 6 l,4-Bis-[(4-methylphenoxy)-acetyl]-piperazinExample 6 1,4-Bis - [(4-methylphenoxy) acetyl] piperazine
Verwendet man bei dem Verfahren des Beispiels 4 an Stelle des o-Krcsols 10,8 g p-Krcsol, so erhält man nach dem Umkristallisieren aus Dimethylformamid und Chloroform das obengenannte Produkt in einer Ausbeute von 13,2 g (69,1%); F. 193 bis 195 C.If, in the process of Example 4, 10.8 g of p-Krcsol are used instead of the o-Krcsol, one obtains after recrystallization from dimethylformamide and chloroform, the above product in one Yield of 13.2 g (69.1%); F. 193 to 195 C.
Analyse für C22H26O4N2:Analysis for C 22 H 26 O 4 N 2 :
Berechnet ... C 69,09, H 6,85, N 7,33%: gefunden .... C 69,85. H 6,75, N 7,22%.Calculated ... C 69.09, H 6.85, N 7.33%: found ... C 69.85. H 6.75, N 7.22%.
35 Beispiel 9
l,4-Bis-[(3-methoxyphenoxy)-acclyl]-pipcrazin 35 Example 9
1,4-bis [(3-methoxyphenoxy) aclyl] pipcrazine
Zu einer Lösung von 9,7 g Piperazin-hexahydrat in 100 ml Aceton wird langsam unter Rühren bei Raumtemperatur eine Lösung von 10 g 3-Mcthoxyphcnoxyacetylchlorid (Kp.1()mm: 127 C) in 20 ml Aceton zugetropft. Nach 2- bis 3stündigem weiterem Rühren werden die ausgefallenen Kristalle abfiltriert, und das Filtrat wird unter vermindertem Druck eingeengt. Der mit den Kristallen vereinigte Rückstand wird nacheinander mit 5%iger Salzsäure, 5%igcr Natronlauge und schließlich mit Wasser gewaschen. Durch Umkristallisieren aus Dioxan erhält man das Endprodukt in Form eines farblosen kristallinen Pulvers in einer Ausbeute von 6,56 g (63,4%): F. i 53 bis 154 C.To a solution of 9.7 g of piperazine hexahydrate in 100 ml of acetone, a solution of 10 g of 3-methoxyphynoxyacetyl chloride (boiling point 1 mm : 127 ° C.) in 20 ml of acetone is slowly added dropwise with stirring at room temperature. After stirring for a further 2 to 3 hours, the precipitated crystals are filtered off and the filtrate is concentrated under reduced pressure. The residue combined with the crystals is washed successively with 5% hydrochloric acid, 5% sodium hydroxide solution and finally with water. Recrystallization from dioxane gives the end product in the form of a colorless crystalline powder in a yield of 6.56 g (63.4%): F. i 53 to 154 C.
Analyse Tür C22H21,O„N2:Analysis door C 22 H 21 , O "N 2 :
Berechnet ... N 6,76°/',,:
gefunden .... N 6,58%.Calculated ... N 6.76 ° / ',,:
found .... N 6.58%.
Ein Gemisch aus 0,85 g Natrium, 100 ml Äthanol und 5 g p-Propylphenol wird mit 4,4 g l,4-Bis-(chloracetyl)-piperazin versetzt. Die Lösung wird unter Rühren erhitzt, bis sie neutral reagiert. Die abgeschiedenen Kristalle werden abfiltriert, mit Wasser gewaschen und aus Äthanol umkristallisierl. Ausbeute: 6,2 g (76,9%): F. 168 bis 169 X. 'A mixture of 0.85 g of sodium, 100 ml of ethanol and 5 g of p-propylphenol is mixed with 4.4 g of 1,4-bis (chloroacetyl) piperazine offset. The solution is heated with stirring until it reacts neutrally. The departed Crystals are filtered off, washed with water and recrystallized from ethanol. Yield: 6.2 g (76.9%): F. 168 to 169 X. '
Analyse RJrC26H34O4N2:Analysis RJrC 26 H 34 O 4 N 2 :
Berechnet ... C 71,20, H 7,82, N 6,39%: gefunden .... C 71,49, H 7,72, N 6,23%.Calculated ... C 71.20, H 7.82, N 6.39%: found .... C 71.49, H 7.72, N 6.23%.
4545
1,4-Bis-(phenoxyacetyl)-piperazin1,4-bis (phenoxyacetyl) piperazine
100 ml Aceton werden mit 11,4g (0,0586 Mol) Pipcrazinhcxahydrat versetzt. Beim Zutropfen von100 ml of acetone are mixed with 11.4 g (0.0586 mol) Pipcrazine hydroxahydrate added. When adding
55 Beispiel 10
1.4-Bis-[(4-methoxyphenoxy)-acctyl]-pipcrazin 55 Example 10
1,4-bis [(4-methoxyphenoxy) acctyl] pipcrazine
Zu einer Lösung von 9,7 g Piperazin-hexahydrat in 100 ml Aceton wird langsam unter Rühren bei Raumtemperatur eine Lösung von 10 g 4-Methoxyphcnoxyacctylchlorid (Kp.1()mm: 124 C) in 20 ml Aceton zugetropft. Das Verfahren wird dann weiter nach Beispiel 9 durchgeführt. Durch Umkristallisieren aus Dioxan erhält man das Endprodukt als farbloses kristallines Pulver in einer Ausbeute von 7,03 g (69.11V0): F. 168 bis 169 C.To a solution of 9.7 g of piperazine hexahydrate in 100 ml of acetone, a solution of 10 g of 4-methoxyphynoxyacctyl chloride (boiling point 1 mm : 124 ° C.) in 20 ml of acetone is slowly added dropwise with stirring at room temperature. The process is then carried out according to Example 9. Recrystallization from dioxane gives the end product as a colorless crystalline powder in a yield of 7.03 g (69.1 1 V 0 ): F. 168 to 169 C.
AiIaIySCrUrC22H26O6N2:AiIaIySCrUrC 22 H 26 O 6 N 2 :
Berechnet ... N 6.76%:
gefunden N 6,83%.Calculated ... N 6.76%:
found N 6.83%.
Claims (2)
Family
ID=
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