CH364267A - Process for the preparation of an addition compound of piperazine and 4-iodothymol - Google Patents
Process for the preparation of an addition compound of piperazine and 4-iodothymolInfo
- Publication number
- CH364267A CH364267A CH5561658A CH5561658A CH364267A CH 364267 A CH364267 A CH 364267A CH 5561658 A CH5561658 A CH 5561658A CH 5561658 A CH5561658 A CH 5561658A CH 364267 A CH364267 A CH 364267A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperazine
- iodothymol
- preparation
- addition compound
- addition
- Prior art date
Links
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title claims description 38
- OUYBTFOUTJAWPZ-UHFFFAOYSA-N 4-iodo-5-methyl-2-propan-2-ylphenol Chemical compound CC(C)C1=CC(I)=C(C)C=C1O OUYBTFOUTJAWPZ-UHFFFAOYSA-N 0.000 title claims description 24
- 150000001875 compounds Chemical class 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 6
- 229960005141 piperazine Drugs 0.000 claims description 18
- 229960003641 piperazine hydrate Drugs 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- JRRBJSPQEVZLPI-UHFFFAOYSA-N piperazin-1-ium;hydroxide Chemical compound O.C1CNCCN1 JRRBJSPQEVZLPI-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000244206 Nematoda Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 3
- 241001465677 Ancylostomatoidea Species 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 241000731736 Rhabdias Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229960003506 piperazine hexahydrate Drugs 0.000 description 1
- VKBJNABNNJYRTK-UHFFFAOYSA-N piperazine;hydrate;hydrochloride Chemical compound O.Cl.C1CNCCN1 VKBJNABNNJYRTK-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
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
- C07D295/02—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 containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung einer Additionsverbindung von Piperazin und 4-Jodthymol
Die Erfindung betrifft ein Verfahren zur Herstellung einer neuen Additionsverbindiung von Piperazin und 4-Jodthymol.
Piperazin ist ein wurmreibendes Mittel, das zwar wenig Sekundärwirkungen aufweist, aber einen unangenehmen Geschmack besitzt und ausserdem hygroskopisch ist und zum Zerfliessen neigt. Um diese Nachteile bei der Herstellun, auszugleichen, wird es im allgemeinen in Form seines Citrats oder Adipats verwendet. Die Verwendung des Citrats oder Adipats beseitigt jedoch lediglich die Schwierigkeiten bei der Herstellung, während die wurmtreibende Wirkung einzig vom Piperazin selbst abhängt.
4-Jodthymol war bisher nur als gewöhnliche chemische Verbindung bekannt. Es wurde nun gefunr den, dass diese Verbindung wurmtreibend gegeniiber Hakenwürmern wirkt und dass das Additionsprodukt von Piperazin und 4-Jodthymol gegen Hakenwürmer, Fadensvürmer und Spulwürmer wiriksam ist, während das Piperazin nur gegen Fadenwürmer und Spulwürmer wirksam ist. Die neue Verbindung ist daher in ihrer Wirkung von allen bisher bekannten wurmtreibenden Mitteln auf-Piperazinbasis völlig verschie- den. Ausserdem verschwindet bei der Zugabe von 4-Jodthymol zum Piperazin der unangenehme Ge schmack des letzteren.
Das Additionsprodukt ist ein praktisch geschmacldoses, stabiles, kristallines Pulver, das sich gut zur Verarbeitung zu Tabletten oder beliebigen andern Zubereitungen eignet.
Die wurmtreibende Wirkung von 4-Jodthymol und des Additionsproduktes von Piperazin und 4-Jodthymol ist aus der folgenden Zusammenstellung er sichtlich :
Resultate von Versuchen gegen den Toadschen Fadenwurm (Rhabdias sp.) in vivo (bei oraler Ver abreichung) Verabreichte Wurmtreibende Wirkung (%) Menge Additionsverbindung von Piperazin
4-Jodthymol (mg/kg) und 4-Jodthymol
300 7, 4 40, 6
500 35, 3 80, 7
800 91,1
Aus dieser Tabelle ergibt sich klar, dass die Addi tionsverbindung eine bedeutend grössere Wirkung besitzt als das 4-Jodthymol allein.
Die LD50 (bei oraler Verabreichung) für eine dd-Serie männlicher Mäuse betrug 2600 mg/kg für 4-Jodthymol und 2667 mg/kg für das Additionsprodukt von Piperazin und 4-Jodthymol.
Gegenstand des vorliegenden Patentes ist demnach ein Verfahren zur Herstellung einer Additionsverbindung von einem Molekül Piperazin mit zwei Molekülen 4-Jodthymol, das dadurch gekennzeichnet ist, dass man Piperazin, ein Piperazinhydrat oder ein Piperazinsalz mit 4-Jodthymol oder einem Alkalisalz des 4-Jodthymols umsetzt.
Dabei kann man beispielsweise so vorgehen, dass man Piperazinhydrat und 4-Jodthymol in einem Alkohol in der Wärme löst und den Alkohol dann entfernt, wobei man die Additionsverbindung in kristalliner Form erhält. Man kann die Additionsverbindung aber auch durch Umsetzung eines organischen oder anorganischen Piperazinsalzes, beispielsweise des Hydrochlorids, Sulfats, Oxalats oder Tartrats, mit 4-Jodthymol in wässriger alkalischer Lösung herstellen.
Die erfindunlgslgemäss hergestellte A, dditionsver- bindung, die aus 1 Molekül Piperazin und 2 Molekülen 4-JodAymol besteht, ist schwer löslich in Wasser und Ligroin, löslich in Alikoholen.
Beispiel 1
49 g Piperazin-Hexahydrat und 69 g 4-Jodthymol werden unter Zugabe von 100 cm3 95%igen Äthanol auf dem Wasserbad erwärmt, bis alles gelöst ist. Dann wird das Athanol entfernt, wobei weisse pulverige Kristalle erhalten werden. Nachldem Umlkristallisie- ren aus Ligroin werden 81 g des Additionsproduktes von Piperazin und 4-Jodthymol erhalten. Smp. 83 bis 85 C ; Ausbeute 90 .
Beispiel 2
Zu einer Lösung von 23 g Natriumhydroxyd in 100 cmS Wasser werden 156 g 4-Hodthymol gegeben und gelöst. Dann werden unter Rühren 50 g Piperazinhydrochloridmonohydrat zugegeben. Gleichzeitig mit dieser Zugabe beginnt die Reaktion, und es werden nach und nach Kristalle gebildet. Diese werden abfiltriert, mit Wasser gewaschen und getrocknet. Nach dem Umkristallisieren aus Ligroin werden 154 g des Additionsproduktes von Piperazin und 4-Jodthymol erhalten. Smp. 83-85 C ; Ausbeute 85 11/o.
Process for the preparation of an addition compound of piperazine and 4-iodothymol
The invention relates to a process for the preparation of a new addition compound of piperazine and 4-iodothymol.
Piperazine is a worming agent that, although it has few secondary effects, has an unpleasant taste and is also hygroscopic and tends to dissolve. To compensate for these disadvantages in production, it is generally used in the form of its citrate or adipate. However, the use of the citrate or adipate only eliminates the difficulties in the preparation, while the worming effect depends solely on the piperazine itself.
4-iodothymol was previously only known as a common chemical compound. It has now been found that this compound has a worming effect against hookworms and that the addition product of piperazine and 4-iodothymol is effective against hookworms, roundworms and roundworms, while piperazine is only effective against roundworms and roundworms. The new compound is therefore completely different in its action from all previously known worm-causing agents based on piperazine. In addition, when 4-iodothymol is added to the piperazine, the unpleasant taste of the latter disappears.
The addition product is a practically flavourful, stable, crystalline powder that is well suited for processing into tablets or any other preparation.
The worming effect of 4-iodothymol and the addition product of piperazine and 4-iodothymol can be seen from the following list:
Results of tests against Toad's nematode (Rhabdias sp.) In vivo (when administered orally) Administered worm-propelling effect (%) Amount of addition compound of piperazine
4-iodothymol (mg / kg) and 4-iodothymol
300 7, 4 40, 6
500 35, 3 80, 7
800 91.1
From this table it is clear that the addition compound has a significantly greater effect than 4-iodothymol alone.
The LD50 (when administered orally) for a dd series of male mice was 2600 mg / kg for 4-iodothymol and 2667 mg / kg for the addition product of piperazine and 4-iodothymol.
The present patent therefore relates to a process for the preparation of an addition compound of one molecule of piperazine with two molecules of 4-iodothymol, which is characterized in that piperazine, a piperazine hydrate or a piperazine salt is reacted with 4-iodothymol or an alkali salt of 4-iodothymol.
One can proceed, for example, that piperazine hydrate and 4-iodothymol are dissolved in an alcohol in the heat and the alcohol is then removed, the addition compound being obtained in crystalline form. The addition compound can also be prepared by reacting an organic or inorganic piperazine salt, for example the hydrochloride, sulfate, oxalate or tartrate, with 4-iodothymol in an aqueous alkaline solution.
The addition compound produced according to the invention, which consists of 1 molecule of piperazine and 2 molecules of 4-iodo-amol, is sparingly soluble in water and ligroin, and soluble in alcohols.
example 1
49 g of piperazine hexahydrate and 69 g of 4-iodothymol are heated on the water bath with the addition of 100 cm3 of 95% ethanol until everything has dissolved. The ethanol is then removed, white powdery crystals being obtained. After recrystallization from ligroin, 81 g of the addition product of piperazine and 4-iodothymol are obtained. M.p. 83 to 85 C; Yield 90.
Example 2
156 g of 4-hodthymol are added to a solution of 23 g of sodium hydroxide in 100 cm of water and dissolved. Then 50 g of piperazine hydrochloride monohydrate are added with stirring. At the same time as this addition, the reaction begins and crystals are gradually formed. These are filtered off, washed with water and dried. After recrystallization from ligroin, 154 g of the addition product of piperazine and 4-iodothymol are obtained. M.p. 83-85 C; Yield 85 11 / o.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2325157 | 1957-09-21 | ||
| JP164258 | 1958-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH364267A true CH364267A (en) | 1962-09-15 |
Family
ID=26334902
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH5561658A CH364267A (en) | 1957-09-21 | 1958-02-07 | Process for the preparation of an addition compound of piperazine and 4-iodothymol |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH364267A (en) |
-
1958
- 1958-02-07 CH CH5561658A patent/CH364267A/en unknown
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