DE292846C - - Google Patents
Info
- Publication number
- DE292846C DE292846C DENDAT292846D DE292846DA DE292846C DE 292846 C DE292846 C DE 292846C DE NDAT292846 D DENDAT292846 D DE NDAT292846D DE 292846D A DE292846D A DE 292846DA DE 292846 C DE292846 C DE 292846C
- Authority
- DE
- Germany
- Prior art keywords
- oxypiperidine
- methyl
- parts
- derivatives
- chloride
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 150000001414 amino alcohols Chemical class 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N Benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 2
- MFSIEROJJKUHBQ-UHFFFAOYSA-N O.[Cl] Chemical compound O.[Cl] MFSIEROJJKUHBQ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- -1 benzoyloxypiperidine chlorohydrate Chemical compound 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drugs Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 description 1
- FFFNUHGMXGAUFY-UHFFFAOYSA-N 4-(4-methylphenoxy)piperidine Chemical compound C1=CC(C)=CC=C1OC1CCNCC1 FFFNUHGMXGAUFY-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- 229930006677 A03BA01 - Atropine Natural products 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N Atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 Atropine Drugs 0.000 description 1
- 229960005015 Local anesthetics Drugs 0.000 description 1
- 229940083877 Local anesthetics for treatment of hemorrhoids and anal fissures for topical use Drugs 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N Phenylisocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- CLSUSRZJUQMOHH-UHFFFAOYSA-L Platinum(II) chloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 description 1
- XQJMXPAEFMWDOZ-BTTYYORXSA-N Tropacocaine Chemical compound O([C@@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-BTTYYORXSA-N 0.000 description 1
- 230000002378 acidificating Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- ZPUCINDJVBIVPJ-BARDWOONSA-N cocaine Natural products O([C@@H]1C[C@H]2CC[C@H](N2C)[C@@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-BARDWOONSA-N 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- LBKPGNUOUPTQKA-UHFFFAOYSA-N ethyl N-phenylcarbamate Chemical compound CCOC(=O)NC1=CC=CC=C1 LBKPGNUOUPTQKA-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229940064003 local anesthetic throat preparations Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000002911 mydriatic Effects 0.000 description 1
- 230000001264 neutralization Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- YNHMMVMSCFNCJS-UHFFFAOYSA-N piperidin-4-yl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1CCNCC1 YNHMMVMSCFNCJS-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N tin hydride Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
KAISERLICHESIMPERIAL
PATENTAMTPATENT OFFICE
Es wurde gefunden, daß man durch Veresterung des 4-Oxypiperidins und seiner am Stickstoff alkylierten Derivate (vgl. Patente 292456 und 292871) mit organischen Säuren zu wertvollen Arzneimitteln (Lokalanästhetica und Mydriatica) gelangen kann. Die Beobachtung ist um so überraschender, da man auf Grund der Atropin-, Cocain- und Tropacocainkonstitution nur von Estern in 2 · 6-Stel lung substituierter Derivate des 4-Oxypiperidins eine solche Wirkung erwarten konnte. Das Verfahren zur Darstellung der neuen Verbindungen besteht darin, daß man das 4-Oxypiperidin oder seine am Stickstoff alkylierten Derivate in üblicher Weise mit organischen Säuren verestert.It has been found that esterifying 4-oxypiperidine and its am Nitrogen alkylated derivatives (see patents 292456 and 292871) with organic acids can obtain valuable drugs (local anesthetics and mydriatic drugs). The observation is all the more surprising, since one due to the atropine, cocaine and tropacocaine constitution derivatives of 4-oxypiperidine substituted only by esters in the 2 · 6 position such an effect could be expected. The procedure for representing the new compounds is to have the 4-Oxypiperidine or its derivatives alkylated on the nitrogen in the customary manner with organic Esterified acids.
400 Teile 4-Oxypiperidinchlorhydrat werden mit 600 Teilen Benzoylchlorid unter Rühren auf 120° erhitzt und einige Stunden bei dieser Temperatur gehalten. Die homogene Flüssigkeit erstarrt auf Zusatz von Äther kristallinisch. Der nach dem Absaugen des Äthers zurückbleibende Rückstand wird aus Alkohol umkristallisiert, aus dem sich das Benzoyloxypiperidinchlorhydrat als dicker Kristallbrei abscheidet. Es schmilzt bei raschem Erhitzen bei etwa 230 °. In Wasser und heißem Alkohol ist es leicht löslich, schwerer in kaltem Alkohol; mit Gold- und Platinchlorid bildet es schwer lösliche Doppelsalze. Das aus dem400 parts of 4-oxypiperidine chlorohydrate are used heated with 600 parts of benzoyl chloride with stirring to 120 ° and a few hours at this Temperature held. The homogeneous liquid solidifies in a crystalline manner on addition of ether. The residue remaining after the ether has been filtered off with suction is recrystallized from alcohol, from which the benzoyloxypiperidine chlorohydrate is formed separates as a thick crystal pulp. It melts at about 230 ° when heated rapidly. In water and hot alcohol it is easily soluble, more difficult in cold alcohol; forms with gold and platinum chloride there are hardly soluble double salts. That from the
Chlorhydrat abgeschiedene freie 4-Benzoyloxypiperidin siedet bei 169 bis 1700 unter 12 mm Druck und bildet ein farbloses, in den üblichen organischen Lösungsmitteln leicht lösliches öl, während es in Wasser bei Zimmertemperatur sich zu· etwa 1 Prozent löst.Free 4-benzoyloxypiperidine separated off from chlorine hydrate boils at 169 to 170 ° under 12 mm pressure and forms a colorless oil which is easily soluble in the usual organic solvents, while it dissolves in water at room temperature to about 1 percent.
Verwendet man an Stelle des Benzoylchlorids im Beispiel 1 das p-Toluylsäurechlorid und arbeitet im übrigen wie dort angegeben, so gelangt man zum 4-p-Toluyloxypiperidin. Sein Chlorhydrat zeigt den Schmelzpunkt 210 °.If, instead of the benzoyl chloride in Example 1, p-toluic acid chloride is used and if the rest of the procedure is as stated there, 4-p-toluyloxypiperidine is obtained. Its hydrochloride shows a melting point of 210 °.
100 Teile N-Methyl-4-oxyperidin (vgl. Patent 292871, Beispiel 1) werden mit der fünffachen Menge Benzoesäureanhydrid im Ölbad bei 120° verschmolzen. Nach beendeter Reaktion wird die Schmelze in verdünnter Salzsäure gelöst, von neutralen und sauren Reaktionsnebenprodukten durch Absaugen und Ausäthern getrennt und dann die Base durch Alkali abgeschieden. Ihr Chlorhydrat zeigt den Schmelzpunkt 215°.100 parts of N-methyl-4-oxyperidin (see patent 292871, Example 1) with five times the amount of benzoic anhydride in an oil bath fused at 120 °. After the reaction has ended, the melt is dissolved in dilute hydrochloric acid dissolved, of neutral and acidic reaction by-products by suction and etherification separated and then deposited the base by alkali. Your chlorohydrate shows the melting point 215 °.
50 Teile N-Äthyl-4-oxypiperidin (vgl. Patent 292871, Beispiel 2) werden mit 200 Teilen trocknem Benzol und 75 Teilen Benzoylchlorid einige Stunden am Rückfluß gekocht. Das ölig abgeschiedene Chlorhydrat, das durch50 parts of N-ethyl-4-oxypiperidine (cf. Patent 292871, Example 2) are mixed with 200 parts dry benzene and 75 parts of benzoyl chloride refluxed for a few hours. The oily chlorine hydrate separated by
Abgießen der Mutterlauge erhalten werden kann, läßt sich durch Aufnahme in absolutem Alkohol und vorsichtigen Zusatz von Äther in schön kristallinischer Form gewinnen. Es schmilzt bei etwa 200 °.Pouring off the mother liquor can be obtained, can be obtained by inclusion in absolute Alcohol and careful addition of ether win in beautiful crystalline form. It melts at around 200 °.
""■■/ / Beispiel 5. "" ■■ / / Example 5.
Verwendet man an Stelle von N-Äthyl-4-pxypiperidin und Benzoylchlorid nach Beispiel 4/ das N-Methyl-4-oxypiperidin und obz^.' /p-Toluylsäurechlorid und arbeitet im /übrigen ähnlich wie dort auf, so erhält man ' d|e /salzsauren Salze des o- und p-Toluyl-N-methyl-4-oxypiperidins vom Schmelzpunkt 208 bzw. 2io°.Used instead of N-ethyl-4-pxypiperidine and benzoyl chloride according to Example 4 / the N-methyl-4-oxypiperidine and obz ^. ' / p-toluic acid chloride and works in / other similar to there, one obtains the hydrochloric acid salts of o- and p-toluyl-N-methyl-4-oxypiperidine with a melting point of 208 or 2io °.
Verwendet man an Stelle der im Beipiel 5 benutzten" Säurechloride das p-Nitrobenzoylchlorid, so erhält man das p-Nitrobenzoyl-N-methyl-4-oxypiperidin, das beim Reduzieren mit Zinn und Salzsäure in der üblichen Weise in die entsprechende Aminoverbindung übergeht. Die p-Nitrobenzoyl-N-methyl-4-oxy- piperidinbase schmilzt bei 1900, die entsprechende Aminobase bei etwa 140 °.If the acid chlorides used in Example 5 are replaced by p-nitrobenzoyl chloride, p-nitrobenzoyl-N-methyl-4-oxypiperidine is obtained, which is converted into the corresponding amino compound in the usual way on reduction with tin and hydrochloric acid p-nitrobenzoyl-N-methyl-4-oxy-piperidine base melts at 190 0, the corresponding amino base at about 140 °.
Molekulare Mengen N-Methyl-4-oxypiperidin und Phenylisocyanat vereinigen sich unter starker Wärmeentwicklung zum Phenylurethan, so daß bei Verarbeitung größerer Mengen gut gekühlt oder ein indifferentes Verdünnungsmittel, wie z. B. Benzol, zugegeben werden muß. Das in Salzsäure gelöste Reaktionsprodukt wird von etwas Diphenylharnstoff abfiltriert. Auf Zusatz von einem Alkali erhält man wieder die freie Base, die nach dem Umkristallisieren mit verdünntem Alkohol den Schmelzpunkt 120 ° zeigt.Molecular amounts of N-methyl-4-oxypiperidine and phenyl isocyanate combine with strong heat development to the phenyl urethane, so that good when processing larger quantities cooled or an inert diluent, such as. B. benzene, are added got to. The reaction product dissolved in hydrochloric acid is made up of a little diphenylurea filtered off. The addition of an alkali gives the free base again, which after the Recrystallization with dilute alcohol shows the melting point 120 °.
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE292846C true DE292846C (en) |
Family
ID=547573
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT292846D Active DE292846C (en) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE292846C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1242231B (en) * | 1956-05-30 | 1967-06-15 | Sandoz Ag | Process for the preparation of new ester-like piperidine compounds |
-
0
- DE DENDAT292846D patent/DE292846C/de active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1242231B (en) * | 1956-05-30 | 1967-06-15 | Sandoz Ag | Process for the preparation of new ester-like piperidine compounds |
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