CH368505A - Process for the preparation of cyano-3-phenothiazine - Google Patents
Process for the preparation of cyano-3-phenothiazineInfo
- Publication number
- CH368505A CH368505A CH120363A CH120363A CH368505A CH 368505 A CH368505 A CH 368505A CH 120363 A CH120363 A CH 120363A CH 120363 A CH120363 A CH 120363A CH 368505 A CH368505 A CH 368505A
- Authority
- CH
- Switzerland
- Prior art keywords
- phenothiazine
- cyano
- preparation
- mixture
- carbamoyl
- Prior art date
Links
- 229950000688 phenothiazine Drugs 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001408 amides Chemical class 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- PMWFJTLZEZSXEO-UHFFFAOYSA-N 10h-phenothiazine-3-carbonitrile Chemical compound C1=CC=C2SC3=CC(C#N)=CC=C3NC2=C1 PMWFJTLZEZSXEO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- TZUBDZSHEZQQBV-UHFFFAOYSA-N 10H-phenothiazine-3-carboxamide Chemical compound C(N)(=O)C=1C=CC=2NC3=CC=CC=C3SC2C1 TZUBDZSHEZQQBV-UHFFFAOYSA-N 0.000 description 1
- ZAZBAXPDYNCBBL-UHFFFAOYSA-N 10h-phenothiazine-3-carboxylic acid Chemical compound C1=CC=C2SC3=CC(C(=O)O)=CC=C3NC2=C1 ZAZBAXPDYNCBBL-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
Procédé de préparation de la cyano-3-phénothiazine La présente invention a pour objet un procédé de préparation de la cyano-3-phénothiazine (numé rotation Beilstein), de formule
EMI0001.0009
Le procédé selon l'invention est caractérisé en ce que l'on déshydrate l'amide de formule
EMI0001.0012
au moyen d'un agent déshydratant, qui peut être de l'anhydride phosphorique,
de l'oxychlorure de phos phore ou du chlorure de thionyle.
La cyano-3-phénothiazine obtenue par le pro cédé selon l'invention est un intermédiaire particu lièrement important pour la préparation de produits doués de propriétés pharmacodynamiques précieuses.
Dans l'exemple ci-après, les points de fusion ont été déterminés au banc Kofler.
<I>Exemple</I> A une solution agitée de 22 g de pentoxyde de phosphore dans<B>150</B> cm3 d'oxychlorure de phosphore, on ajoute 18,1 g de carbamoyl-3-phénothiazine et on chauffe le mélange à reflux pendant deux heures et demie. Le mélange réactionnel est versé avec pré caution sur de la glace et le solide précipité est extrait au chloroforme. Les extraits secs sont éva porés et le résidu solide est sublimé à 224-2400 sous 0,2 à 0,4 mm de mercure. On obtient la cyano- 3-phénothiazine qui, après recristallisation dans la méthyléthylcétone, fond à 2040.
La carbamoyl-3-phénothiazine de départ peut être préparée comme suit A un mélange agité de 67 g de carboxy-3-phéno- thiazine et de 900 cm3 de benzène sec, on ajoute par portions à 5-7 en 30 minutes, 62,8 g de penta- chlorure de phosphore. Une fois l'addition terminée, on agite le mélange sans le refroidir, pendant 2 heu res, et on le verse sur un excès d'ammoniaque et de glace. Après repos de plusieurs heures, le solide est filtré, lavé à plusieurs reprises avec de l'eau et séché.
Le produit brut est recristallisé dans un mélange d'éthanol et d'isopropanol ; on obtient des aiguilles jaunes de carbamoyl-3-phénothiazine, fon dant à 232,5-233,5.
Process for preparing 3-cyano-phenothiazine The present invention relates to a process for preparing 3-cyano-phenothiazine (Beilstein rotation number), of formula
EMI0001.0009
The process according to the invention is characterized in that the amide of formula is dehydrated
EMI0001.0012
by means of a dehydrating agent, which may be phosphorus pentoxide,
phosphorus oxychloride or thionyl chloride.
The cyano-3-phenothiazine obtained by the process according to the invention is a particularly important intermediate for the preparation of products endowed with valuable pharmacodynamic properties.
In the example below, the melting points were determined on the Kofler bench.
<I> Example </I> To a stirred solution of 22 g of phosphorus pentoxide in <B> 150 </B> cm3 of phosphorus oxychloride, 18.1 g of 3-carbamoyl-phenothiazine are added and heated the mixture at reflux for two and a half hours. The reaction mixture is carefully poured onto ice and the precipitated solid is extracted with chloroform. The dry extracts are evaporated and the solid residue is sublimated at 224-2400 under 0.2 to 0.4 mm of mercury. This gives cyano-3-phenothiazine which, after recrystallization from methyl ethyl ketone, melts at 2040.
The starting carbamoyl-3-phenothiazine can be prepared as follows To a stirred mixture of 67 g of 3-carboxy-phenothiazine and 900 cm3 of dry benzene is added in portions at 5-7 over 30 minutes, 62, 8 g of phosphorus pentachloride. When the addition is complete, the mixture is stirred without cooling it for 2 hours, and it is poured onto an excess of ammonia and ice. After standing for several hours, the solid is filtered off, washed several times with water and dried.
The crude product is recrystallized from a mixture of ethanol and isopropanol; yellow needles of carbamoyl-3-phenothiazine are obtained, melting at 232.5-233.5.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR733428 | 1957-03-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH368505A true CH368505A (en) | 1963-04-15 |
Family
ID=8704197
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH120463A CH368506A (en) | 1957-03-07 | 1957-12-18 | Process for the preparation of cyano-3-phenothiazine |
| CH5389257A CH368507A (en) | 1957-03-07 | 1957-12-18 | Process for the preparation of cyano-3-phenothiazine |
| CH120363A CH368505A (en) | 1957-03-07 | 1957-12-18 | Process for the preparation of cyano-3-phenothiazine |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH120463A CH368506A (en) | 1957-03-07 | 1957-12-18 | Process for the preparation of cyano-3-phenothiazine |
| CH5389257A CH368507A (en) | 1957-03-07 | 1957-12-18 | Process for the preparation of cyano-3-phenothiazine |
Country Status (1)
| Country | Link |
|---|---|
| CH (3) | CH368506A (en) |
-
1957
- 1957-12-18 CH CH120463A patent/CH368506A/en unknown
- 1957-12-18 CH CH5389257A patent/CH368507A/en unknown
- 1957-12-18 CH CH120363A patent/CH368505A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CH368507A (en) | 1963-04-15 |
| CH368506A (en) | 1963-04-15 |
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