CH361282A - Process for the preparation of phenothiazines - Google Patents
Process for the preparation of phenothiazinesInfo
- Publication number
- CH361282A CH361282A CH361282DA CH361282A CH 361282 A CH361282 A CH 361282A CH 361282D A CH361282D A CH 361282DA CH 361282 A CH361282 A CH 361282A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- preparation
- phenothiazines
- toluene
- acylphenothiazine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 150000002990 phenothiazines Chemical class 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- FRCDSGBFLHMDBG-UHFFFAOYSA-N 1-(2-chloro-5-oxophenothiazin-10-yl)-3-(dimethylamino)propan-1-one Chemical compound C1=C(Cl)C=C2N(C(=O)CCN(C)C)C3=CC=CC=C3S(=O)C2=C1 FRCDSGBFLHMDBG-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 γ-chloropropyl Chemical group 0.000 description 2
- IPKGONQXQKUIQI-UHFFFAOYSA-N 1-(10h-phenothiazin-3-yl)propan-1-one Chemical compound C1=CC=C2SC3=CC(C(=O)CC)=CC=C3NC2=C1 IPKGONQXQKUIQI-UHFFFAOYSA-N 0.000 description 1
- JYNZCQHQWDOOKH-UHFFFAOYSA-N 3-(3-chlorophenothiazin-10-yl)-n,n-dimethylpropan-1-amine Chemical compound ClC1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 JYNZCQHQWDOOKH-UHFFFAOYSA-N 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229940066767 systemic antihistamines phenothiazine derivative Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von Phenothiazinen Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von Verbindungen der Formel
EMI0001.0004
in der Ac einen Acylrest, X und Y Wasserstoff atome oder einwertige Substituenten, A eine Alkyl'en- gruppe und R1 und R2 Alkylgruppen oder R1 und RI,
zusammen mit dem Stickstoffatom einen gege benenfalls ein weiteres N- oder ein O-Heteroatom aufweisenden 5- oder 6gliedrigen Ring bedeuten.
Die genannten Verbindungen erwiesen sich im Tierversuch dem 3-Chlor-10-(y-dimethylamino-pro- pyl)-phenothiazin vor allem in bezug auf ihre blut drucksenkenden Eigenschaften deutlich überlegen. Sie zeigen ausserdem hervorragende ganglien- blockierende und potenzierende Eigenschaften.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man ein Acylphenothiazin der Formel 1
EMI0001.0026
mit einem reaktionsfähigen Ester eines Alkohols der Formel Hal-A-OH umsetzt und anschliessend das Halogenatom durch Umsetzung mit einem Amin der Formel
EMI0001.0028
durch eine Aminogruppe ersetzt.
Die so hergestellten Phenothiazin-Derivate kön nen entweder als solche oder in Form ihrer Salze oder als quartäre Ammoniumverbindungen zur An wendung gebracht werden. <I>Beispiel</I> <B><I>51</I>9</B> 3-Propionyl-phenothiazin werden in 400 cm3 Toluol mit 12 g Natriumamid 4 Stunden am Rück fluss gekocht.
Dann lässt man abkühlen, tropft 49 g p-Toluolsulfo-(y-chlorpropyl)-ester in 200 cm3 Toluol zu und kocht noch eine Stunde am Rückfluss. Es wird abgesaugt, mit Toluol gewaschen, die vereinten Toluolfiltrate erst mit Wasser, mit verdünnter Säure und wiederum mit Wasser gewaschen und nach dein Trocknen eingedampft.
Der Rückstand, 3-Propionyl- 10-(y-chlorpropyl)-phenthiazin, wird mit 18g Di- methylamin in 400 cm3 Toluol 12 .Stunden im Auto klav auf 120 erhitzt.
Nach dem Abkühlen wird ab gesaugt, mit Toluol gewaschen, mit verdünnter Essigsäure die Base ausgeschüttelt, mit Alkali frei gemacht, mi Äther aufgenommen und nach dem Trocknen und Abdampfen des Äthers der Rückstand destilliert: man erhält 3-Propionyl-10-(y-dimethyl- amino-propyl)-phenthiazin vom Kp. .,l 240-245 C.
Process for the preparation of phenothiazines The present invention relates to a process for the preparation of compounds of the formula
EMI0001.0004
in which Ac is an acyl radical, X and Y are hydrogen atoms or monovalent substituents, A is an alkyl group and R1 and R2 are alkyl groups or R1 and RI,
together with the nitrogen atom denote a 5- or 6-membered ring which may optionally contain a further N- or an O-heteroatom.
In animal experiments, the compounds mentioned proved to be clearly superior to 3-chloro-10- (γ-dimethylamino-propyl) -phenothiazine, particularly with regard to their blood pressure-lowering properties. They also show excellent ganglion-blocking and potentiating properties.
The process according to the invention is characterized in that an acylphenothiazine of the formula 1
EMI0001.0026
with a reactive ester of an alcohol of the formula Hal-A-OH and then the halogen atom by reaction with an amine of the formula
EMI0001.0028
replaced by an amino group.
The phenothiazine derivatives produced in this way can be used either as such or in the form of their salts or as quaternary ammonium compounds. <I> Example </I> <B> <I> 51 </I> 9 </B> 3-propionyl-phenothiazine are refluxed for 4 hours in 400 cm3 of toluene with 12 g of sodium amide.
It is then allowed to cool, 49 g of p-toluenesulfo- (γ-chloropropyl) ester in 200 cm3 of toluene are added dropwise and the mixture is refluxed for a further hour. It is filtered off with suction, washed with toluene, the combined toluene filtrates are washed first with water, with dilute acid and again with water and, after drying, evaporated.
The residue, 3-propionyl-10- (γ-chloropropyl) -phenthiazine, is heated to 120 for 12 hours in a car with 18 g of dimethylamine in 400 cm3 of toluene.
After cooling, it is suctioned off, washed with toluene, shaken out the base with dilute acetic acid, freed with alkali, taken up with ether and, after drying and evaporation of the ether, the residue is distilled: 3-propionyl-10- (γ-dimethyl) is obtained - Amino-propyl) -phenthiazine of bp., l 240-245 C.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE361282X | 1955-09-07 | ||
| DE120656X | 1956-06-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH361282A true CH361282A (en) | 1962-04-15 |
Family
ID=25750768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH361282D CH361282A (en) | 1955-09-07 | 1956-07-23 | Process for the preparation of phenothiazines |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH361282A (en) |
-
1956
- 1956-07-23 CH CH361282D patent/CH361282A/en unknown
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