CH280320A - Process for producing a spiro-thiobarbituric acid compound. - Google Patents
Process for producing a spiro-thiobarbituric acid compound.Info
- Publication number
- CH280320A CH280320A CH280320DA CH280320A CH 280320 A CH280320 A CH 280320A CH 280320D A CH280320D A CH 280320DA CH 280320 A CH280320 A CH 280320A
- Authority
- CH
- Switzerland
- Prior art keywords
- spiro
- thiobarbituric acid
- acid compound
- producing
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 1,1-dicarbethoxy-2-methyl-5-ethyl-cyclopentane Chemical compound 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 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 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung einer Spiro-thiobarbitursäureverbindung. Gegenstand der vorliegenden Erfindung ist ein Verfahren zur Herstellung einer neuen Spiro-thiobarbitursäureverbindung, nämlich der Spiro-2-methyl-5-äthyl-cyclopent.an-(1),5'- thiobarbitursäure.
Die neue Verbindung besitzt geringe Toxi- zität und weist wertvolle sedative und ein schläfernde Eigenschaften auf; dabei ist sie in kleinen Dosen wirksam und ruft schon nach kurzer Zeit Anästhesie hervor.
Das Verfahren gemäss der Erfindung ist dadurch gekennzeichnet, dass man 1,1-Dicarb- äthoxy-2-methyl-5-äthyl-cyclopentan mit Thio- harnstoff umsetzt. Die neue Verbindung ist eine kristalline Substanz vom ungefähren Smp. 172 bis 173 C. Die Umsetzung erfolgt gemäss nachstehender Gleichung
EMI0001.0013
Die neue Barbitursäure kann in Salze über geführt werden, z.
B. durch Umsetzung mit Kaliumalkoholat in wasserfreier Alkohol lösung oder mittels aliumhydroxyd in wäs seriger Alkohollösung in das Kaliumsalz. Durch Verdampfen der Lösung des Salzes erhält man das trockene Salz.
Zit pharmazeutischen Zwecken wird ein lösliches Salz, z. B. das Natriumsalz, bevorzugt. Die neue Verbindung besitzt in der sauren Form eine verhältnismässig niedrige Wasser löslichkeit. Wenn auch die saure Form sich zur oralen und parenteralen Verabreichung eignet, wird man trotzdem ein wasserlösliches Material vorziehen, weshalb man die Verbin dung vorzugsweise in Form ihrer wasserlös lichen Salze anwenden wird.
<I>Beispiel:</I> 103,2 g 1,1-Dicarbäthoxy-2-methyl-5-äthyl- cyclopentan werden einer Lösung von 46 g Thioharnstoff in aus 27,9 g Natrium und 350 cm3 absolutem Alkohol hergestellter Na triiunmethylatlösung zugesetzt. Die Lösung wird gerührt und während etwa sechs Stunden unter Rückfluss sieden gelassen.
Man vertreibt das Methanol durch Destillation und löst den Rückstand, welcher die Spiro-2-methyl-5-äthyl- cyelopentan-(1),5'-thiobarbitursäure in Form des Natriumsalzes enthält, in etwa. 500 em3 Wasser. Die Lösung wird zur Entfernung von nicht umgesetztem Ester mehrere 3Zale mit Äther extrahiert. Die Lösung wird hierauf mit Salzsäure angesäuert.
Die in fester Form aus fallende Spiro-2-methyl-5-äthyl-cyclopentan (1),5'-thiobarbitursäure wird abfiltriert. iNfan reinigt die Thiobarbitursäure, indem man sie in verdünntem Natriumhydroxyd löst, die Lö sung mit Entfärbungskohle behandelt und die Thiobarbitursäure durch Neutralisierung der Lösung durch Zugabe eines Überschusses an festem Kohlendioxyd wieder ausfällt.
Der Nie derschlag aus der Thiobarbitursäure wird durch Umkristallisieren aus verdünntem Ätha- nol weiter gereinigt.
Die auf diese Weise hergestellte Spiro-2- methyl - 5 - ät.hyl - cyclopent.an - (1) , 5'-thiobarbi- tursäure schmilzt bei etwa 172 bis 173 C. Die Analyse ergibt einen Stickstoffgehalt von 11,49 %, während der berechnete Wert für den Stickstoffgehalt 11,66% beträgt.
Process for producing a spiro-thiobarbituric acid compound. The present invention relates to a process for the production of a new spiro-thiobarbituric acid compound, namely spiro-2-methyl-5-ethyl-cyclopent.an- (1), 5'-thiobarbituric acid.
The new compound is of low toxicity and has valuable sedative and drowsy properties; it is effective in small doses and induces anesthesia after a short time.
The process according to the invention is characterized in that 1,1-dicarb-ethoxy-2-methyl-5-ethyl-cyclopentane is reacted with thiourea. The new compound is a crystalline substance with an approximate melting point of 172 to 173 C. The reaction takes place according to the following equation
EMI0001.0013
The new barbituric acid can be converted into salts, for.
B. by reaction with potassium alcoholate in anhydrous alcohol solution or by means of aluminum hydroxide in wäs seriger alcohol solution in the potassium salt. The dry salt is obtained by evaporating the solution of the salt.
For pharmaceutical purposes, a soluble salt, e.g. B. the sodium salt is preferred. The new compound has a relatively low water solubility in its acidic form. Even if the acidic form is suitable for oral and parenteral administration, a water-soluble material will nevertheless be preferred, which is why the compound is preferably used in the form of its water-soluble salts.
Example: 103.2 g 1,1-dicarbethoxy-2-methyl-5-ethyl-cyclopentane are added to a solution of 46 g thiourea in sodium methylate solution prepared from 27.9 g sodium and 350 cm3 absolute alcohol added. The solution is stirred and refluxed for about six hours.
The methanol is driven off by distillation and the residue, which contains the spiro-2-methyl-5-ethyl-cyelopentane (1), 5'-thiobarbituric acid in the form of the sodium salt, is roughly dissolved. 500 em3 water. The solution is extracted several 3Zals with ether to remove unreacted ester. The solution is then acidified with hydrochloric acid.
The spiro-2-methyl-5-ethyl-cyclopentane (1), 5'-thiobarbituric acid which precipitates in solid form is filtered off. iNfan cleans the thiobarbituric acid by dissolving it in dilute sodium hydroxide, treating the solution with decolorizing charcoal and the thiobarbituric acid precipitating again by neutralizing the solution by adding an excess of solid carbon dioxide.
The precipitate from the thiobarbituric acid is further purified by recrystallization from dilute ethanol.
The spiro-2-methyl - 5 - ethyl - cyclopent.an - (1), 5'-thiobarbituric acid produced in this way melts at about 172 to 173 ° C. The analysis shows a nitrogen content of 11.49%, while the calculated value for the nitrogen content is 11.66%.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US280320XA | 1949-03-19 | 1949-03-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH280320A true CH280320A (en) | 1952-01-15 |
Family
ID=21841177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH280320D CH280320A (en) | 1949-03-19 | 1949-06-14 | Process for producing a spiro-thiobarbituric acid compound. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH280320A (en) |
-
1949
- 1949-06-14 CH CH280320D patent/CH280320A/en unknown
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