CH269654A - Process for the preparation of a basic thioether. - Google Patents
Process for the preparation of a basic thioether.Info
- Publication number
- CH269654A CH269654A CH269654DA CH269654A CH 269654 A CH269654 A CH 269654A CH 269654D A CH269654D A CH 269654DA CH 269654 A CH269654 A CH 269654A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- piperidino
- basic
- chloride
- formula
- Prior art date
Links
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
- C07D295/084—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 with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
<B>Verfahren zur Darstellung eines</B> basischen Thioäthers. Es ist aus der pharmakologischen Litera tur bekannt, dass in physiologisch wirksamen Substanzen der Ersatz von Sauerstoff durch Schwefel zu therapeutisch interessanten Ver bindungen führt (R. 0. Roblin jr. Chem. Review, 35, 255 [19461). Manchmal wird nur eine quantitative Änderung der Wirksamkeit erreicht; es sind aber auch bereits Fälle be kannt, wo durch den Austausch der gebann ten Elemente sogar pharmakologische Anta gonisten erhalten werden.
Bisher fehlen Veröffentlichungen über die Antihistaminwirkung von basischen Äthern, welche im Molekül Schwefel enthalten. Bei der Darstellung einiger solcher Verbindungen wurde überraschend festgestellt, dass sie bei unveränderter Antihistaminwirkung eine er heblich geringere Toxizität aufweisen als die entsprechenden Sauerstoffverbindungen und daher therapeutisch besonders wertvoll sind.
Es wurde gefunden, dass basische Aralkyl- thioäther der allgemeinen Formel:
EMI0001.0014
wobei X = Wasserstoff oder eine Phenyl- gruppe und NR, = den Rest eines zyklischen sekundären Amins bedeuten, hergestellt wer den können durch die Kondensation eines Mercaptans der Formel I mit einem hetero- cyclischen sekundären Amin der Formel 1I, und zwar durch die Reaktion des Natrium- derivates des Mercaptans mit dem Chlorid des sekundären Amins.
EMI0001.0024
oder durch die Reaktion des Natriumderiva- tes eines Mercaptans der Formel III mit einem Chlorid der Formel IV.
EMI0001.0029
Gegenstand vorliegender Erfindung ist ein Verfahren zur Darstellung des Diphenyl- methyl - ss - piperidino - äthylthioäthers, welches dadurch gekennzeichnet ist,
dass das Natritun- derivat des ss-Piperidino-äthylmercaptans mit Diphenylmethylchlorid kondensiert wird. Das erhaltene Endprodukt bildet farblose Kristalle mit einem Schmelzpunkt von 176 bis 177 C (unkorrigiert). Es ist in Wasser leicht lös lich.
Beispiel: 2,3 g Natrium (0,1 Mol) wurden in 100 cmg absolutem Äthanol aufgelöst und all mählich 13,3 g (0,1 Mol) fl-Piperidino-äthyl- mercaptan zugesetzt. Zum Reaktionsgut wur den tropfenweise 20 g Diphenylmethylchlorid hinzugefügt, das Ganze 12 Stunden bei Raumtemperatur stehengelassen und sodann während 3 Stunden am Rüekflusskühler zum Sieden erhitzt.
Nach dein Erkalten wurde das ausgeschiedene Chlornatrium abfiltriert. Das Filtrat wurde mit 500 eins absolutem Äther verdünnt, blank filtriert und tropfenweise mit der berechneten Menge von alkoholischer Salzsäure versetzt. Das ausgefällte Kondensa tionsprodukt wurde abfiltriert und aus Iso- propanol umkristallisiert.
Die Analyse bestä- tigte die Bruttoformel C"oH"NSCl des Hy- drochlorids des Diphenylmethyl-fl-piperidino- äthylthioäthers, eine Substanz in Gestalt von farblosen Kristallen vom Schmp. 176 bis 177 C (nichtkorrigiert), welche in Wasser leicht löslich ist.
Das erhaltene Produkt entspricht der Strukturformel
EMI0002.0015
und ist eine neue Verbindung, welche sich klinisch bewährt hat als untoxisches Anti- histaminicum von hoher Wirksamkeit.
<B> Method for the preparation of </B> a basic thioether. It is known from the pharmacological literature that the replacement of oxygen by sulfur in physiologically active substances leads to therapeutically interesting compounds (R. 0. Roblin Jr. Chem. Review, 35, 255 [19461). Sometimes only a quantitative change in effectiveness is achieved; but there are also already known cases where even pharmacological antagonists are obtained by exchanging the banned elements.
So far there have been no publications on the antihistamine effect of basic ethers which contain sulfur in the molecule. In the presentation of some such compounds, it was surprisingly found that, with unchanged antihistamine action, they have a considerably lower toxicity than the corresponding oxygen compounds and are therefore of particular therapeutic value.
It has been found that basic aralkyl thioethers of the general formula:
EMI0001.0014
where X = hydrogen or a phenyl group and NR = the radical of a cyclic secondary amine mean, who can be prepared by the condensation of a mercaptan of the formula I with a heterocyclic secondary amine of the formula 1I, by the reaction of the Sodium derivatives of the mercaptan with the chloride of the secondary amine.
EMI0001.0024
or by the reaction of the sodium derivative of a mercaptan of the formula III with a chloride of the formula IV.
EMI0001.0029
The present invention is a process for the preparation of diphenylmethyl - ss - piperidino - ethylthioether, which is characterized by
that the sodium derivative of β-piperidino-ethyl mercaptan is condensed with diphenylmethyl chloride. The end product obtained forms colorless crystals with a melting point of 176 to 177 C (uncorrected). It is easily soluble in water.
Example: 2.3 g of sodium (0.1 mol) were dissolved in 100 cmg of absolute ethanol and gradually 13.3 g (0.1 mol) of fl-piperidino-ethyl-mercaptan were added. 20 g of diphenylmethyl chloride were added dropwise to the reaction mixture, the whole was left to stand for 12 hours at room temperature and then heated to boiling for 3 hours on a reflux condenser.
After cooling down, the precipitated sodium chloride was filtered off. The filtrate was diluted with 500 units of absolute ether, filtered until it was clear and the calculated amount of alcoholic hydrochloric acid was added dropwise. The precipitated condensation product was filtered off and recrystallized from isopropanol.
The analysis confirmed the gross formula C "oH" NSCl of the hydrochloride of diphenylmethyl-fl-piperidinoethylthioether, a substance in the form of colorless crystals with a melting point of 176 to 177 ° C. (uncorrected) which is easily soluble in water.
The product obtained corresponds to the structural formula
EMI0002.0015
and is a new compound which has proven itself clinically as a non-toxic antihistamine of high effectiveness.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS269654X | 1947-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH269654A true CH269654A (en) | 1950-07-15 |
Family
ID=5451709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH269654D CH269654A (en) | 1947-07-01 | 1948-06-28 | Process for the preparation of a basic thioether. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH269654A (en) |
-
1948
- 1948-06-28 CH CH269654D patent/CH269654A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1670849B2 (en) | PROCESS FOR THE PREPARATION OF 8-ACYLAMINO-1,2,3,4-TETRAHYDROISOCHINOLINES | |
| DE2938302A1 (en) | NEW DERIVATIVES OF 3- (AMINOAETHYL) - PHENOLS AND THEIR SALTS, THEIR PRODUCTION PROCESS, THEIR USE AS A MEDICINAL PRODUCT AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM | |
| DE1545575C2 (en) | N, N'-Bis- square bracket to 3 "(3 ', 4', 5'-trimethoxybenzoyloxy) -propyl square bracket to -homopiperazine | |
| DE1445186B2 (en) | 3,3'-di-2-imidazolin-2-yl-carbanilide | |
| CH622491A5 (en) | Process for the preparation of novel hydroxypropylamines | |
| DE1154119B (en) | Process for the preparation of 2- (2 ', 4', 6'-trimethylbenzyl) -1, 3-diazacyclopentene- (2) and its salts | |
| DE949742C (en) | Process for the preparation of N-allyl normorphine from normorphine and allyl halide | |
| CH269654A (en) | Process for the preparation of a basic thioether. | |
| DE2144077C3 (en) | New Hydroxyäthylaminoalkylpiperazines and processes for their preparation | |
| DE2166270C3 (en) | Nicotinoylaminoethanesulfonyl-2amino-thiazole | |
| DE1952800C3 (en) | 3,6-dimethyl-1,2,3,4,4a, 9a-hexahydro-gamma-carboline dihydrochloride | |
| DE829894C (en) | Process for the preparation of new derivatives of 1,8-naphthyridine-4-carboxylic acids | |
| DE1670143C3 (en) | ||
| DE837534C (en) | Process for the preparation of pyridinium compounds | |
| AT251585B (en) | Process for the preparation of new 6,7-dihydro-5H-pyrrolo- [3,4-d] -pyrimidines | |
| DE896047C (en) | Process for the preparation of salicylic acid derivatives | |
| DE1182237B (en) | Process for the preparation of 10- [4'-hydroxy-4'-hydroxyalkylpiperidinoalkyl] -phenthiazine derivatives | |
| AT278808B (en) | Process for the preparation of new 4-acyl-3,4-dihydro-2 (1H) -quinoxalinone derivatives | |
| AT211302B (en) | Process for the preparation of new monoalkylaminopropionyl toluidides and their salts | |
| AT282593B (en) | PROCESS FOR THE PREPARATION OF NEW RACEMIC OR OPTICALLY ACTIVE (1-2'-NITRILOPHENOXY) -2-HYDROXY-3-ISOPROPYLAMINOPROPANE AND ITS SALTS | |
| AT265530B (en) | Process for the preparation of new isoquinoline derivatives | |
| AT237597B (en) | Process for the production of new propylamine derivatives and their salts | |
| DE2538593C3 (en) | m-Trifluoromethylthio-phenethylamine derivatives, process for their preparation and pharmaceuticals containing these compounds | |
| DE920546C (en) | Process for the preparation of derivatives of 3- (4'-oxyphenyl) -3- (4 "-oxy-3" -aminomethyl-phenyl) -oxindole | |
| DE1024968B (en) | Process for the preparation of 7-ketonyl-8-amino-theophyllines |