CH295833A - Process for the preparation of 4- (N-phenyl-N-benzyl) -amino-1-methyl-piperidine. - Google Patents
Process for the preparation of 4- (N-phenyl-N-benzyl) -amino-1-methyl-piperidine.Info
- Publication number
- CH295833A CH295833A CH295833DA CH295833A CH 295833 A CH295833 A CH 295833A CH 295833D A CH295833D A CH 295833DA CH 295833 A CH295833 A CH 295833A
- Authority
- CH
- Switzerland
- Prior art keywords
- base
- piperidine
- benzyl
- phenyl
- amino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 239000000155 melt Substances 0.000 claims description 4
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 3
- 229940073608 benzyl chloride Drugs 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000004927 clay Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002585 base Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 238000007514 turning Methods 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
-
- 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung von 4-(N-Phenyl-N-benzyl)-amino-l-methyl-piperidin. Inr, 4- (N-Phenyl-N-benzyl) -amino-l-methyl- piperidin wurde ehre Verbindung gefunden, die starke antiallergische Wirkungen besitzt, bei gleichzeitiger guter Verträglichkeit.
Die neue Verbindung wird erfindungsge mäss dadurch hergestellt, dass man 1-Meth@=1- piperidon-(4) mit. Anilin umsetzt, die erhal tene Schiffsehe Base zum sekundären Amirr reduziert und das letztere mit Benzylchlorid zum tertiären Amin umsetzt. Für die Reduk tion der Schiffsehen Base ist die Isolierung derselben nicht. erforderlich. Daher kann durch die Einwirkung des Reduktionsmittels auf die Reaktionsmischung Kondensation und Reduktion zu einem Arbeitsgang verbunden werden.
Das Verfahrensprodukt Soll als Arznei- rrrittel Verwendung finden.
Beispiel: Anil <I>des</I> 1-lletltyl <I>-</I> piperidon <I>- (1) :</I> 80 g 1-llet.lryl-piperidon-(4) und 70 g Anilin wer den in 250 eins Toluol unter Zusatz einiger Tropfen Eisessig am Wasserabseheider bis zur Abtrennung der theoretischen Wasser menge (12,7 cm-3.) gekocht. Darauf wird das Toluol abdestilliert. und der Rückstand im Vakuum fraktioniert, wobei bei Kp13 156 C 118 g eines schwach gelb gefärbten Öls erhal ten werden.
<I>4 - N -</I> Phenyl <I>-</I> amilto <I>-1-</I> rrtethyl <I>-</I> piperidin: 100 g Anil des 1-llethyl-piperidon-(4) wer- den mit 30 g aktivierten Aluminiumspänen in 300 eins Methanol und 60 eins Wasser am Rückfluss 8 Stunden gekocht.
Darauf wird vonr Bodenkörper abgetrennt, das Lösungs mittel verdampft und der Rückstand im Vakuum fraktioniert, wobei bei Kp13 163 bis 165 C 95 g eines farblosen Öls erhalten wer den, das sofort kristallin erstarrt. Die aus Dibrityläther umkristallisierte Base schmilzt bei 87 C; das Dihydrochlorid der Base schmilzt bei 246 C.
<I>1 -</I> (N-Pheityl <I>-N- b</I> eitz-yl)- amino -1-7netibyl- piperidin: 95 g 4-N-Phenyl-amino-l-methyl- piperidin werden in 300 eins Benzol mit 22 g pulverisiertem Natriumamid unter Durchlei ten von Stickstoff so lange am Rückfluss ge kocht, bis die Ammoniakentwicklungbeendigt ist.
Darauf werden zu dem kochenden Reak tionsprodukt allmählich 64 g Benzylchlorid binzugetropft und anschliessend noch einige Stunden gekocht. Die erkaltete Lösung wird reit Wasser ausgeschüttelt, mit. Pottasche ge trocknet und das Lösungsmittel verdampft, worauf die hinterbleibende Base in einer Aus beute von 128 g zu Kristallen erstarrt, die nach dem 1Jmkrist.allisieren aus Dibutyläther bei 115 C schmelzen.
Die Base ist in Alko holen, Aceton und Äthern löslich, in Wasser und Kohlenwasserstoffen unlöslich. Das Monohydrochlorid der Base vom Schmelz punkt 205 C kristallisiert mit 2 Molekülen. Kristallwasser; das Dihydroehlorid der Base schmilzt bei 189 C.
Process for the preparation of 4- (N-phenyl-N-benzyl) -amino-1-methyl-piperidine. Inr, 4- (N-phenyl-N-benzyl) -amino-1-methyl-piperidine was found to be an excellent compound that has strong anti-allergic effects and is well tolerated at the same time.
The new compound is prepared according to the invention by 1-Meth @ = 1- piperidone- (4) with. The aniline is converted, the Schiff base obtained is reduced to the secondary amine and the latter is converted to the tertiary amine with benzyl chloride. The isolation of the ship's base is not necessary for the reduction. required. Therefore, by the action of the reducing agent on the reaction mixture, condensation and reduction can be combined into one operation.
The process product should be used as a medicinal product.
Example: Anil <I> des </I> 1-lletltyl <I> - </I> piperidon <I> - (1): </I> 80 g 1-llet.lryl-piperidon- (4) and 70 g of aniline who boiled in 250 one toluene with the addition of a few drops of glacial acetic acid on the water separator until the theoretical amount of water (12.7 cm-3.) has been removed. The toluene is then distilled off. and the residue fractionated in vacuo, 118 g of a pale yellow oil being obtained at bp13 156 ° C.
<I> 4 - N - </I> Phenyl <I> - </I> amilto <I> -1- </I> rrtethyl <I> - </I> piperidine: 100 g anil des 1-llethyl- piperidon- (4) are refluxed for 8 hours with 30 g of activated aluminum turnings in 300 liters of methanol and 60 liters of water.
The sediment is then separated off, the solvent is evaporated and the residue is fractionated in vacuo, 95 g of a colorless oil being obtained at bp13 163 to 165 C, which immediately solidifies in crystalline form. The base recrystallized from dibrityl ether melts at 87 C; the dihydrochloride of the base melts at 246 C.
<I> 1 - </I> (N-Pheityl <I> -N- b </I> eitz-yl) - amino -1-7netibyl-piperidine: 95 g of 4-N-phenyl-amino-1-methyl - Piperidine are refluxed in 300 liters of benzene with 22 g of powdered sodium amide while passing nitrogen through until the evolution of ammonia has ceased.
Then 64 g of benzyl chloride are gradually added dropwise to the boiling reaction product and then boiled for a few hours. The cooled solution is shaken out with water. Potash is dried and the solvent evaporates, whereupon the remaining base solidifies to crystals in a yield of 128 g, which melt after 1Jmkrist.allisierung from dibutyl ether at 115 C.
The base is soluble in alcohol, acetone and ethers, and insoluble in water and hydrocarbons. The monohydrochloride of the base with a melting point of 205 ° C. crystallizes with 2 molecules. Crystal water; the dihydrochloride of the base melts at 189 C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE295833X | 1949-07-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH295833A true CH295833A (en) | 1954-01-15 |
Family
ID=6090179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH295833D CH295833A (en) | 1949-07-20 | 1950-07-11 | Process for the preparation of 4- (N-phenyl-N-benzyl) -amino-1-methyl-piperidine. |
Country Status (4)
| Country | Link |
|---|---|
| AT (1) | AT170868B (en) |
| CH (1) | CH295833A (en) |
| DK (1) | DK78744C (en) |
| GB (1) | GB700097A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE130851T1 (en) * | 1991-03-14 | 1995-12-15 | Basf Ag | SUBSTITUTED N-PHENYLPIPERIDINE AND DRUGS THEREOF. |
-
1950
- 1950-07-05 DK DK223150A patent/DK78744C/en active
- 1950-07-07 AT AT170868D patent/AT170868B/en active
- 1950-07-11 CH CH295833D patent/CH295833A/en unknown
- 1950-07-20 GB GB18157/50A patent/GB700097A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AT170868B (en) | 1952-04-10 |
| GB700097A (en) | 1953-11-25 |
| DK78744C (en) | 1955-01-17 |
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