DEP0036249DA - Process for the production of thiosemicarbazones - Google Patents
Process for the production of thiosemicarbazonesInfo
- Publication number
- DEP0036249DA DEP0036249DA DEP0036249DA DE P0036249D A DEP0036249D A DE P0036249DA DE P0036249D A DEP0036249D A DE P0036249DA
- Authority
- DE
- Germany
- Prior art keywords
- weight
- parts
- thiosemicarbazones
- hydrazine
- rhodanide
- 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.)
- Expired
Links
- 229940042396 direct acting antivirals thiosemicarbazones Drugs 0.000 title claims description 6
- 150000003584 thiosemicarbazones Chemical class 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
- 150000002576 ketones Chemical class 0.000 claims description 8
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 6
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- FQUDPIIGGVBZEQ-UHFFFAOYSA-N acetone thiosemicarbazone Chemical compound CC(C)=NNC(N)=S FQUDPIIGGVBZEQ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 229910000377 hydrazine sulfate Inorganic materials 0.000 description 2
- 239000012493 hydrazine sulfate Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 description 2
- 235000011151 potassium sulphates Nutrition 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Description
Dr. Clemens Lutter, Wuppertal, und Dr. Ernst Cauer, LeverkusenDr. Clemens Lutter, Wuppertal, and Dr. Ernst Cauer, Leverkusen
Kn/Sch Leverkusen, den 11« Febr. 1949Kn / Sch Leverkusen, February 11, 1949
Verfahren zur Herstellung von ThiosemicarbazonenProcess for the production of thiosemicarbazones
wurde gefunden, daß sich die Thiosemicarbazone von. Ketonen besonders einfach herstellen lassen, wenn man Hydrazinrhodanid^zweckmäßig in wäßriger Lösung, gegebenenfalls in Anwesenheit weiterer Lösungs·= oder Verdünnungsmittel, mit Ketonen in der A'ärme umsetzt»it was found that the thiosemicarbazones of. Ketones are particularly easy to manufacture if you Hydrazinrhodanid ^ expediently in aqueous solution, optionally in the presence of other solvents or diluents with Converts ketones in the arm »
Bei der bisiicr bekannten Arbeitsweise zur Herstellung solcher Thiosemicarbazone sind zwei Arbeitsgänge, nämlich die Umlagerung des Hydrazinrhodanids zum Thiosemicarbazid und die Umsetzung mit dem Keton, notwendig. Hinzu kommt, daß die Umlagerung des Hydrazinrhodanids zum Thiosemicarbazid in wäßriger Lösung langsam und nur bis zur Erreichung eines Gleichgewichtszustandes verläuft; die Reinigung des entstandenen Thiosemicarbazide ist wegen der notwendigen Abtrennung anorganischer Salze verlustreich. Demgegenüber vollzieht sich die Umlagerung des Hydrazinrhodanids in Gegenwart eines Ketons fast augenblicklich und mit Ausbeuten bis zu 9o $. Das hierbei entstehende Thiosemicarbazid wird nämlich sofort vom Keton in Form des Ketonthiosemicarbazons abgefangen tind aus dem Gleichgewicht entfernt. Infolge seiner Schwerlöslichkeit wird das entstandene Ketonthioseniicarbazon sofort in einem Reinheitsgrad erhalten, der ein.e Reinigung für weitere Umsetzungen unnötig machtP Der fast quantitative Verlauf der Umsetzung zu Thiosemicarbazon ist überraschend, da mit einer Umsetzung des Hydrazins mit den Ketonen zu Azinen gerechnet werden mußte und ein derartiger Verlauf der Umsetzung, wie festgestellt wurde, bei Verwendung von Aldehyden auch tatsächlich vorherrscht*In the previously known procedure for the preparation of such thiosemicarbazones, two operations are necessary, namely the rearrangement of the hydrazine rhodanide to the thiosemicarbazide and the reaction with the ketone. In addition, the rearrangement of hydrazine rhodanide to thiosemicarbazide proceeds slowly in aqueous solution and only until a state of equilibrium is reached; the purification of the resulting thiosemicarbazide is costly because of the necessary separation of inorganic salts. In contrast, the rearrangement of the hydrazine rhodanide in the presence of a ketone takes place almost instantaneously and with yields of up to 90 $. The resulting thiosemicarbazide is caught immediately by the ketone in the form of the ketone thiosemicarbazone and is removed from the equilibrium. As a result of its low solubility, the resulting Ketonthioseniicarbazon will immediately receive a degree of purity ein.e cleaning for further reactions makes unnecessary P The almost quantitative course of the reaction to thiosemicarbazone is surprising, as was to be expected with a conversion of hydrazine with ketones to azines and Such a course of the conversion, as has been found, actually prevails when using aldehydes *
Die erfindungsgemäß erhaltenen Thiosemicarbazone sollen als Zwischenprodukte für Heilmittel Verwendung finden«,The thiosemicarbazones obtained according to the invention are intended to be used as intermediates for medicinal products «,
Le A 120Le A 120
Eine Lösung von 97 Gewichtsteilen Kaliumrhodanid in 2oo Gewichtsteilen Wasser wird mit einer Lösung von 81 Gewichtsteilen neutralen Hydrazinsulfats in 2oo Gewichtsteilen Wasser vermischt und kurze Zeit auf 9o° erwärmt. Man kühlt ab und saugt von abgeschiedenen Kaliumsulfat ab» Das Filtrate das das Hydraζjnrhodanid enthält, wird auf 6o erwärmt. Bei dieser Temperatur läßt man im Laufe weniger Minuten 75 Gewichtsteile Aceton zulaufen. SFach kurzer Zeit beginnt die Abscheidung des Aceton-Thiosemicarbazons in exothermer Reaktion» Man kühlt ab, saugt den Niederschlag ab und wäscht mit wenig eiskaltem lasser nach«A solution of 97 parts by weight of potassium rhodanide in 200 parts by weight of water is mixed with a solution of 81 Parts by weight of neutral hydrazine sulfate mixed in 2oo parts by weight of water and heated to 90 ° for a short time. You cool off and sucks off the precipitated potassium sulphate. The filtrate containing the hydraζjnrhodanid is heated to 6o. at 75 parts by weight of acetone are allowed to run in at this temperature in the course of a few minutes. The separation begins after a short time of acetone thiosemicarbazone in an exothermic reaction. It is cooled, the precipitate is filtered off with suction and washed with a little ice cold lasser «
Ausbeutet 12o Gewichtsteile Aceton-Thiosemicarbazon vom Schmelzpunkt löo0.'Exploits 12o parts by weight of acetone thiosemicarbazone with a melting point Löo 0th '
578 Gewichtsteile der wie bei Beispiel 1 hergestellt ten Mischung von Hydrazinsulfat- und Kaliumrhodanidlooung werden
nach dem Erwärmen ^auf 9o° abgekühlt und mit 2oo Gewichtsteilen Methanol versetzt. Man saugt vom Kaliumsulfat ab und
erwärmt die wäßrig-methanolische Hydrazinrhodanidlösung mit 98 Gewichtsteilen Cyclohexanon einige Zeit am Rückfluß« Fach
dem Srkalten wird das ausgeschiedene Cyelohexanon-Thiosemicarbazon isolierte
Ausbeute« 14o Gewichtsteile vom Schmelzpunkt 159°.578 parts by weight of the mixture of hydrazine sulfate and potassium rhodanide lounges prepared as in Example 1 are cooled to 90 ° after heating and 2oo parts by weight of methanol are added. The potassium sulfate is filtered off with suction and the aqueous-methanolic hydrazine rhodanide solution is refluxed for some time with 98 parts by weight of cyclohexanone
Yield «140 parts by weight with a melting point of 159 °.
Claims (1)
Family
ID=
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