DE1468283C - - Google Patents
Info
- Publication number
- DE1468283C DE1468283C DE19631468283 DE1468283A DE1468283C DE 1468283 C DE1468283 C DE 1468283C DE 19631468283 DE19631468283 DE 19631468283 DE 1468283 A DE1468283 A DE 1468283A DE 1468283 C DE1468283 C DE 1468283C
- Authority
- DE
- Germany
- Prior art keywords
- dibenzo
- dimethylsulfamoyl
- isomer
- benzene
- dimethylaminopropylidene
- 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
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- QPJORFLSOJAUNL-UHFFFAOYSA-N dibenzo[a,d][7]annulene Chemical class C1=CC2=CC=CC=C2CC2=CC=CC=C21 QPJORFLSOJAUNL-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000002588 toxic Effects 0.000 claims 1
- 231100000331 toxic Toxicity 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- -1 3-dimethylsulfamoyl-5- (3-dimethylaminopropylidene) - 5 H - dibenzo [a, d] cycloheptene hydrogen oxalate Chemical compound 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000003000 nontoxic Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- KMRMBJFKDZYLAN-UHFFFAOYSA-N 11-[3-(dimethylamino)propylidene]-N,N-dimethyldibenzo[1,3-e:1',2'-f][7]annulene-2-sulfonamide Chemical compound C1=CC2=CC=C(S(=O)(=O)N(C)C)C=C2C(=CCCN(C)C)C2=CC=CC=C21 KMRMBJFKDZYLAN-UHFFFAOYSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
- 102100000129 CHURC1 Human genes 0.000 description 2
- 101710014631 CHURC1 Proteins 0.000 description 2
- OEWBBZXCPSULTG-UHFFFAOYSA-N ClC1=CC2=C(C=CC3=C(C2=CCCN(C)C)C=C(C=C3)S(N(C)C)(=O)=O)C=C1 Chemical class ClC1=CC2=C(C=CC3=C(C2=CCCN(C)C)C=C(C=C3)S(N(C)C)(=O)=O)C=C1 OEWBBZXCPSULTG-UHFFFAOYSA-N 0.000 description 2
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N Cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N Thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N Trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000005712 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000001257 hydrogen Chemical group 0.000 description 2
- 229910052739 hydrogen Chemical group 0.000 description 2
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229940075930 picrate Drugs 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002936 tranquilizing Effects 0.000 description 2
- 239000003204 tranquilizing agent Substances 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- IXNZARLZBMCANF-UHFFFAOYSA-N 2-chloro-5,6-dihydrodibenzo[3,1-[7]annulen-11-one Chemical compound C1CC2=CC=CC=C2C(=O)C2=CC(Cl)=CC=C21 IXNZARLZBMCANF-UHFFFAOYSA-N 0.000 description 1
- 229960000583 Acetic Acid Drugs 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N Acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- OXMNPBBADIOGAZ-UHFFFAOYSA-N CN(S(=O)(=O)C=1C=CC2=C(C(C3=C(C=C2)C=CC=C3)(O)CCCN(C)C)C1)C Chemical compound CN(S(=O)(=O)C=1C=CC2=C(C(C3=C(C=C2)C=CC=C3)(O)CCCN(C)C)C1)C OXMNPBBADIOGAZ-UHFFFAOYSA-N 0.000 description 1
- JHNTXVXZXZPYQQ-UHFFFAOYSA-N ClC1=CC2=C(C=CC3=C(C2(O)CCCN(C)C)C=C(C=C3)S(N(C)C)(=O)=O)C=C1 Chemical compound ClC1=CC2=C(C=CC3=C(C2(O)CCCN(C)C)C=C(C=C3)S(N(C)C)(=O)=O)C=C1 JHNTXVXZXZPYQQ-UHFFFAOYSA-N 0.000 description 1
- JURKNVYFZMSNLP-UHFFFAOYSA-N Cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N Picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000001430 anti-depressive Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960003572 cyclobenzaprine Drugs 0.000 description 1
- 238000006298 dechlorination reaction Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N fumaric acid Chemical compound OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-M maleate(1-) Chemical compound OC(=O)\C=C/C([O-])=O VZCYOOQTPOCHFL-UPHRSURJSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-L maleate(2-) Chemical compound [O-]C(=O)\C=C/C([O-])=O VZCYOOQTPOCHFL-UPHRSURJSA-L 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940114148 picric acid Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229950002929 trinitrophenol Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
SO7NSO 7 N
CH,CH,
CH,CH,
CHCH7CH7NCHCH 7 CH 7 N
CH,CH,
CH,CH,
in der X Chlor oder Wasserstoff, sowie deren nichttoxische Salze und Isomeren.in which X is chlorine or hydrogen, as well as their non-toxic salts and isomers.
2. /5-Isomeres von 3-Dimethylsulfamoyl-5-(3-dimethylaminopropyliden) - 5 H - dibenzo[a,d]cyclohepten-hydrogenoxalat. 2. / 5-isomer of 3-dimethylsulfamoyl-5- (3-dimethylaminopropylidene) - 5 H - dibenzo [a, d] cycloheptene hydrogen oxalate.
3. Verfahren zur Herstellung der Verbindungen nach Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise eine Verbindung der allgemeinen Formel3. Process for the preparation of the compounds according to claim 1, characterized in that a compound of the general formula is used in a manner known per se
SO7NSO 7 N
,CH3 , CH 3
^CH3
CH3 ^ CH 3
CH 3
OH CH2CH2CH2NOH CH 2 CH 2 CH 2 N
mit dehydratisierenden Mitteln behandelt und gegebenenfalls in ein nichttoxisches Salz überführt und gegebenenfalls in die Isomeren spaltet.treated with dehydrating agents and optionally converted into a non-toxic salt and optionally splits into the isomers.
4. Arzneimittel, gekennzeichnet durch einen Gehalt an einer Verbindung gemäß Anspruch 1.4. Medicament, characterized by a content of a compound according to claim 1.
Gegenstand der Erfindung sind 5H-Dibenzo[a,d]-cycloheptenderivate der allgemeinen FormelThe invention relates to 5H-dibenzo [a, d] -cycloheptene derivatives the general formula
4 SO7N 4 SO 7 N
,CH3 j-, CH 3 j-
^CH3
CH3
CHCH2CH2N^ CH 3
CH 3
CHCH 2 CH 2 N
CH3
in der X Chlor oder Wasserstoff, sowie deren nicht-CH 3
in which X is chlorine or hydrogen, as well as their non-
CH,CH,
SO7NSO 7 N
OH CH7CH7CH7NOH CH 7 CH 7 CH 7 N
CH3
CH,CH 3
CH,
CH,CH,
mit dehydratisierenden Mitteln behandelt und gegebenenfalls in ein nichttoxisches Salz überführt und gegebenenfalls in die Isomeren spaltet.treated with dehydrating agents and optionally converted into a non-toxic salt and optionally splits into the isomers.
Die Wasserabspaltung kann mit Hilfe üblicherweise verwendeter wasserabspaltender Mittel, wie Acetylchlorid, Essigsäureanhydrid oder Thionylchlorid, durchgeführt werden.The dehydration can be carried out with the aid of commonly used dehydrating agents, such as Acetyl chloride, acetic anhydride or thionyl chloride.
Die Herstellung der Ausgangsverbindungen für das erfindungsgemäße Verfahren kann auf nachstehende Weise erfolgen: Ausgehend von 10,11-Dihydro - 3 - chlor - 5 H - dibenzo[a,d]cyclohepten - 5 - on erhält man durch Umsetzung mit einer Halogensulfonsäure das entsprechende'10,1 l-Dihydro-3-halogensulfonyl-7-chlor-keton, das man dann mit einem Dialkylamin kondensiert. Das erhaltene 10,11-Dihydro-3-alkylsulfamol-7-chlor-keton setzt man dann nach Dehydrierung der 10,11-Bindung und gegebenenfalls nach Entchlorierung in der 7-Stellung mit einem entsprechenden 3-Alkylaminopropylmagnesiumhalogenid um und hydrolysiert das erhaltene Grignard-Addukt.The preparation of the starting compounds for the process according to the invention can be based on the following How to proceed: Starting from 10,11-dihydro - 3 - chloro - 5 H - dibenzo [a, d] cyclohepten - 5 - one the corresponding 10.1 l-dihydro-3-halosulfonyl-7-chloro-ketone is obtained by reaction with a halosulfonic acid, which is then condensed with a dialkylamine. The 10,11-dihydro-3-alkylsulfamol-7-chloro-ketone obtained one then sets after dehydration of the 10,11 bond and, if appropriate after dechlorination in the 7-position with a corresponding 3-alkylaminopropyl magnesium halide around and hydrolyzed the Grignard adduct obtained.
Die erfindungsgemäß erhältlichen Verbindungen besitzen sowohl Tranquilizer-Wirksamkeit als auch Antidepressionswirksamkeit. Zusätzlich besitzen einige der Verbindungen auch Antihistaminwirkung.The compounds obtainable according to the invention have both tranquilizer activity and Antidepressant effectiveness. In addition, some of the compounds also have antihistamine effects.
Die erfindungsgemäß erhältlichen Verbindungen können als geometrische Isomere existieren. Die Trennung dieser Isomeren kann nach üblichen Arbeitsweisen, wie es in den Beispielen erläutert ist, erzielt werden. Bei einigen Verbindungen wurde gefunden, daß eine Form therapeutisch merklich aktiver als die andere ist. Dies trifft insbesondere für 3-Dimethylsulfamoyl - 5 - (3 - dimethylaminopropyliden)-5 H-dibenzo[a,d]cyclohepten zu, bei welchem die β-Έοττα die aktivere ist. Als erfindungsgemäße Verbindungen seien beispielsweise das α- und das ß-lsomere von 7-Chlor-5-(3-dimethylaminopropyliden)-3 - dimethylsulfamoyl - 5 H - dibenzo[a,d]cycloheptenhydrogen-maleinat und das /S-Isomere von 7-Chlor-5-(3-dimethylaminopropyliden)-3-dimethylsulfamoyl- 5 H-dibenzo[a,d]cyclohepten-picrat genannt.The compounds obtainable according to the invention can exist as geometric isomers. The separation of these isomers can be achieved by customary procedures, as explained in the examples. For some compounds, one form has been found to be significantly more therapeutically active than the other. This applies in particular to 3-dimethylsulfamoyl - 5 - (3 - dimethylaminopropylidene) -5 H-dibenzo [a, d] cycloheptene, in which the β-Έοττα is the more active. Examples of compounds according to the invention are the α- and the ß-isomer of 7-chloro-5- (3-dimethylaminopropylidene) -3 - dimethylsulfamoyl -5 H - dibenzo [a, d] cycloheptene hydrogen maleate and the / S isomer of 7-chloro-5- (3-dimethylaminopropylidene) -3-dimethylsulfamoyl-5 H-dibenzo [a, d] cycloheptenepicrate called.
Die neuen Verbindungen sind als Tranquilizer erheblich wirksamer als das bekannte Cyclobenzaprin. Die erfindungsgemäß hergestellten Verbindungen werden vorzugsweise in Form ihrer nichttoxischen Säureadditionssalze verabreicht.The new compounds are considerably more effective as tranquilizers than the well-known cyclobenzaprine. The compounds prepared according to the invention are preferably in the form of their non-toxic Acid addition salts administered.
3-Dimethylsulfamoyl-5-(3-dimethylaminopropyliden)-5 H-dibenzo[a,d]cyclohepten3-Dimethylsulfamoyl-5- (3-dimethylaminopropylidene) -5 H -dibenzo [a, d] cycloheptene
Eine Lösung von 2,72 g (0,00175 Mol) 3-Dimethylsulfamoyl - 5 - (3 - dimethylaminopropyl) - 5 - hydroxy-5H-dibenzo[a,d]cyclohepten in 20 ml Trifluoressigsäure und 12 ml Trifluoressigsäureanhydrid wird 1 Stunde unter Rückfluß erhitzt. Nach einer weiteren Stunde bei Zimmertemperatur werden die Lösungsmittel unter vermindertem Druck verdampft. Der zurückbleibende Sirup wird mit Wasser behandelt, in einem Eisbad abgekühlt, mit Natriumhydroxyd basisch gemacht und mit Benzol extrahiert. Durch Verdampfen des gewaschenen Benzolextrakts erhält .man 2,7 g ölige Base. Das Hydrogenoxalat wird durch Behandlung einer Lösung der Base in Isopropylalkohol mit einer Lösung eines schwachen Überschusses Oxalsäure in Isopropylalkohol hergestellt. Die Ausbeute an 3-Dimethylsulfamoyl-5-(3-dimethylaminopropyliden) - 5 H - dibenzo[a,d]cyclohepten - hydrogenoxalat vom F. = 192 bis 2000C (Zers.) beträgt 2,9 g (90,5%).A solution of 2.72 g (0.00175 mol) of 3-dimethylsulfamoyl - 5 - (3 - dimethylaminopropyl) - 5 - hydroxy-5H-dibenzo [a, d] cycloheptene in 20 ml of trifluoroacetic acid and 12 ml of trifluoroacetic anhydride is added for 1 hour Heated to reflux. After a further hour at room temperature, the solvents are evaporated off under reduced pressure. The remaining syrup is treated with water, cooled in an ice bath, basified with sodium hydroxide and extracted with benzene. Evaporation of the washed benzene extract gives 2.7 g of an oily base. The hydrogen oxalate is prepared by treating a solution of the base in isopropyl alcohol with a solution of a slight excess of oxalic acid in isopropyl alcohol. The yield of 3-dimethylsulfamoyl-5- (3-dimethylaminopropylidene) - 5 H - dibenzo [a, d] cyclohepten - hydrogen oxalate, mp = 192-200 0 C (dec.) Is 2.9 g (90.5% ).
Dieses Material, ein Gemisch von geometrischen Isomeren, wird mit 300 ml siedendem Isopropylalkohol verrieben. Das unlösliche α-Isomere (1,45 g) wird gesammelt und wiederholt aus absolutem Methanol umkristallisiert, bis ein konstanter Schmelzpunkt von 222 bis 223° C (Zers.) erreicht ist.This material, a mixture of geometric isomers, is made with 300 ml of boiling isopropyl alcohol rubbed in. The insoluble α-isomer (1.45 g) is collected and repeated from absolute methanol recrystallized until a constant melting point of 222 to 223 ° C (decomp.) is reached.
Analyse: C22H26O2N2S · C2H2O4.Analysis: C 22 H 26 O 2 N 2 S • C 2 H 2 O 4 .
Berechnet ... C 61,00, H 5,97, N 5,93%;
gefunden ... C 60,74, H 5,91, N 5,89%.Calculated ... C 61.00, H 5.97, N 5.93%;
found ... C 60.74, H 5.91, N 5.89%.
Das wie oben beschrieben erhaltene Isopropylalkoholfiltrat wird auf die Hälfte des Volumens eingeengt und abgekühlt. Das ß-lsomere kristallisiert in einer Ausbeute von 1,18 g, F. = 194 bis 196°C (Zers.), aus. Ein konstanter Schmelzpunkt von 198 bis 199° C (Zers.) wird nach wiederholtem Umkristallisieren aus einem Gemisch von absolutem Äthanol und absolutem Äther und aus Isopropylalkohol erreicht. t The isopropyl alcohol filtrate obtained as described above is concentrated to half its volume and cooled. The β-isomer crystallizes out in a yield of 1.18 g, mp = 194 to 196 ° C. (decomp.). A constant melting point of 198 to 199 ° C (decomp.) Is reached after repeated recrystallization from a mixture of absolute ethanol and absolute ether and from isopropyl alcohol. t
Analyse: C22H26O2N2S · C2H2O4.Analysis: C 22 H 26 O 2 N 2 S • C 2 H 2 O 4 .
Berechnet ... C 61,00, H 5,97, N 5,93%;
gefunden ... C 60,92, H 6,09, N 5,87%.Calculated ... C 61.00, H 5.97, N 5.93%;
Found ... C 60.92, H 6.09, N 5.87%.
4545
(A) 7-Chlor-5-(3-dimethylaminopropyliden)-3-di-(A) 7-chloro-5- (3-dimethylaminopropylidene) -3-di-
methylsulfamoyl-5 H-dibenzo[a,d]cycloheptenmethylsulfamoyl-5 H -dibenzo [a, d] cycloheptene
(gemischte geometrische Isomere)(mixed geometric isomers)
Eine Lösung von 1,72 g (0,0040 Mol) 7-Chlor-5 - (3 - dimethylaminopropyl) - 3 - dimethylsulfamoyl-5 - hydroxy -5 H - dibenzo[a,d]cyclohepten in 12 ml Eisessig wird in einem Eisbad abgekühlt und mit wasserfreiem Chlorwasserstoff 5 Minuten lang gesättigt. 1,63 g (0,016 Mol) Essigsäureanhydrid werden dann zugegeben, und die Lösung wird auf einem Dampfbad 2,5 Stunden erhitzt. Nach Abkühlen auf Zimmertemperatur wird die Lösung mit 17 ml Wasser verdünnt, mit 50 ml Benzol bedeckt, in einem Eisbad abgekühlt und mit 10n-Natriumhydroxyd basisch gemacht. Die Benzolschicht wird abgetrennt und die wäßrige Schicht zweimal mit je 35 ml Benzol extrahiert. Die vereinigten Extrakte werden mit Entfärbungskohle gekocht und filtriert. Das Filtrat wird mit Wasser gewaschen und über Natriumsulfat getrocknet. Dann wird das Benzol unter vermindertem Druck verdampft. Die gemischten geometrischen Isomeren von 7 - Chlor - 5 - (3 - dimethylaminopropyliden)-3-dimethylsulfamoyl-5H-dibenzo[a,d]cyclo- hepten werden als gelbes öl in quantitativer Ausbeute (1,67 g) erhalten.A solution of 1.72 g (0.0040 mol) of 7-chloro-5 - (3 - dimethylaminopropyl) -3 - dimethylsulfamoyl-5 - hydroxy -5 H - dibenzo [a, d] cycloheptene in 12 ml of glacial acetic acid is cooled in an ice bath and with Saturated anhydrous hydrogen chloride for 5 minutes. 1.63 g (0.016 moles) of acetic anhydride will be used then added and the solution heated on a steam bath for 2.5 hours. After cooling down At room temperature the solution is diluted with 17 ml of water, covered with 50 ml of benzene, in an ice bath cooled and made basic with 10N sodium hydroxide. The benzene layer is separated and the aqueous layer extracted twice with 35 ml of benzene each time. The combined extracts are decolorized with charcoal boiled and filtered. The filtrate is washed with water and dried over sodium sulfate. Then the benzene is evaporated under reduced pressure. The mixed geometric Isomers of 7 - chloro - 5 - (3 - dimethylaminopropylidene) -3-dimethylsulfamoyl-5H-dibenzo [a, d] cyclo- hepten are obtained as a yellow oil in quantitative yield (1.67 g).
(B) α-Isomeres von 7-Chlor-5-(3-dimethylaminopropyliden)-3-dimethylsuIfamoyl-5H-dibenzo[a,d]- (B) α-isomer of 7-chloro-5- (3-dimethylaminopropylidene) -3-dimethylsulfamoyl-5H-dibenzo [a, d] -
cycloheptencyclohepten
Das Gemisch von geometrischen Isomeren aus Stufe A wird in 3 ml absolutem Äthanol gelöst und mit einer Lösung von 0,49 g (0,0042 Mol) Maleinsäure in 1 ml absolutem Äthanol behandelt. 16 ml wasserfreier Äther werden bis zur beginnenden Trübung zugegeben, und ein gelbbrauner Niederschlag der gemischten geometrischen Isomeren vom F. = 147 bis 156°C wird in 91,5%iger Ausbeute (1,95 g) erhalten. Eine Kristallisation dieses Materials liefert 1,21 g des Hydrogenmaleinats des α-Isomeren vom F. = 166 bis 1700C. Die Mutterlauge von dieser gelben Festsubstanz wird zur Herstellung des ß-lsomeren, wie im folgenden beschrieben, verwendet. Das Hydrogenmaleinat wird aus absolutem Äthanol umkristallisiert, bis ein konstanter Schmelzpunkt von 174 bis 175,5° C erreicht ist.The mixture of geometric isomers from step A is dissolved in 3 ml of absolute ethanol and treated with a solution of 0.49 g (0.0042 mol) of maleic acid in 1 ml of absolute ethanol. 16 ml of anhydrous ether are added until the onset of cloudiness, and a yellow-brown precipitate of the mixed geometric isomers with a temperature of 147 to 156 ° C. is obtained in 91.5% yield (1.95 g). Crystallization of this material provides 1.21 g of the Hydrogenmaleinats of the α-isomer, mp = 166 to 170 0 C. The mother liquor of this yellow solid substance is used for the preparation of ß-lso mers as described in the following. The hydrogen maleate is recrystallized from absolute ethanol until a constant melting point of 174 to 175.5 ° C is reached.
Analyse: C22H25ClN2O2S ■ C4H4O4. Berechnet ... C 58,58, H 5,48, N 5,26%; gefunden ... C 58,82, H 5,73, N 5,13%.Analysis: C 22 H 25 ClN 2 O 2 S ■ C 4 H 4 O 4 . Calculated ... C 58.58, H 5.48, N 5.26%; found ... C 58.82, H 5.73, N 5.13%.
(C) /S-Isomeres von 7-Chlor-5-(3-dimethylaminopropyliden)-3-dimethylsulfamoyl-5H-dibenzo[a,d]- (C) / S-isomer of 7-chloro-5- (3-dimethylaminopropylidene) -3-dimethylsulfamoyl-5H-dibenzo [a, d] -
cycloheptencyclohepten
Die Mutterlauge aus der ersten Kristallisation des Maleinats der gemischten geometrischen Isomeren aus Stufe A wird unter vermindertem Druck zur Trockne eingedampft. Der braune ölige Rückstand wird in 10 ml Wasser gelöst, und die Lösung wird alkalisch gemacht und dreimal mit je 20 ml Benzol extrahiert. Die vereinigten Extrakte werden gewaschen und dann untei vermindertem Druck zur Trockne eingedampft. Die Base des /f-Isomeren wird als gelbes öl in einer Menge von 0,56 g erhalten. Die Base wird in das Oxalat unter Verwendung eines 5%igen molaren Überschusses der Säure in ab-* solutem Äthanol übergeführt. Das Oxalat, das bei 184,5° C unter Zersetzung^ schmilzt, wird in Wasser gelöst und mit einem 5%igen molaren Überschuß Pikrinsäure in einem gleichen Volumen Äthanol behandelt. Das erhaltene gelbe Pikrat schmilzt bei 238,5 bis 239° C unter Zersetzung. Durch Umkristallisieren aus n-Propylalkohol-Wasser erhält man eine Substanz, die bei 240 bis 240,5° C unter Zersetzung schmilzt.The mother liquor from the first crystallization of the maleate of mixed geometric isomers from stage A is evaporated to dryness under reduced pressure. The brown oily residue is dissolved in 10 ml of water and the solution is made alkaline and three times with 20 ml of benzene each time extracted. The combined extracts are washed and then brought to dryness under reduced pressure evaporated. The base of the / f isomer is called yellow oil obtained in the amount of 0.56 g. The base is converted into the oxalate using a 5% molar excess of the acid converted into absolute ethanol. The oxalate that is used in 184.5 ° C with decomposition ^ melts, is dissolved in water and with a 5% molar excess Picric acid treated in an equal volume of ethanol. The yellow picrate obtained melts at 238.5 to 239 ° C with decomposition. By recrystallization a substance is obtained from n-propyl alcohol / water which decomposes at 240 to 240.5 ° C melts.
Analyse: C22H25ClN2O2S · C6H3N3O7. Berechnet ... C 52,05, H 4,37, N 10,84%; gefunden ... C 52,13, N 4,61, N 10,59%.Analysis: C 22 H 25 ClN 2 O 2 S • C 6 H 3 N 3 O 7 . Calculated ... C 52.05, H 4.37, N 10.84%; Found ... C 52.13, N 4.61, N 10.59%.
(D) Herstellung der Base des /S-Isomeren von(D) Preparation of the base of the / S isomer of
7-Chlor-5-(3-dimethylaminopropyliden)-3-dimethylsulfamoyl-5H-dibenzo[a,d]cyclohepten 7-chloro-5- (3-dimethylaminopropylidene) -3-dimethylsulfamoyl-5H-dibenzo [a, d] cycloheptene
250 mg des Pikrats des /S-Isomeren werden in 20 ml 5 n-Lithiumhydroxydlösung und 150 ml Benzol250 mg of the picrate of the / S isomer are in 20 ml of 5N lithium hydroxide solution and 150 ml of benzene
i 468 283i 468 283
5 65 6
suspendiert und 6 Stunden mechanisch geschüttelt. mit 5%iger Natriumhydroxydlösung alkalisch ge-suspended and mechanically shaken for 6 hours. made alkaline with 5% sodium hydroxide solution
Die Benzolschicht wird abgetrennt und mit 5 η-Li- macht und zweimal mit je 10 ml Benzol extrahiert,The benzene layer is separated off and extracted with 5 η-Li power and twice with 10 ml of benzene each time,
thiumhydroxyd und dann mit Wasser gewaschen. Die vereinigten Extrakte werden mit Wasser ge-thiumhydroxyd and then washed with water. The combined extracts are mixed with water
Nach Verdampfen des Benzols unter vermindertem waschen, über wasserfreiem Natriumsulfat getrocknetAfter evaporating the benzene under reduced washing, drying over anhydrous sodium sulfate
Druck wiegt der braune ölige Rückstand 330 mg. 5 und unter vermindertem Druck eingedampft. DerPressure weighs the brown oily residue 330 mg. 5 and evaporated under reduced pressure. the
Das öl wird zwischen 5 ml 0,1 η-Salzsäure und 8 ml gelbe ölige Rückstand der Base des /3-Isomeren wiegtThe oil is weighed between 5 ml of 0.1 η hydrochloric acid and 8 ml of yellow oily residue of the base of the / 3-isomer
Benzol verteilt. Die wäßrige Schicht wird abgetrennt, 140 mg (88%).Benzene distributed. The aqueous layer is separated, 140 mg (88%).
Claims (1)
allgemeinen Formel1. 5 H - Dibenzo [a, d] cycloheptene derivatives
general formula
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US225864A US3306934A (en) | 1962-09-24 | 1962-09-24 | 5-(aminopropylidene)-and 5-hydroxy-5-(aminopropyl)-3-dialkylsulfamoyl-5h-dibenzo[a,d] cycloheptenes |
| US22586462 | 1962-09-24 | ||
| DEM0058228 | 1963-09-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE1468283A1 DE1468283A1 (en) | 1968-11-28 |
| DE1468283C true DE1468283C (en) | 1973-05-30 |
Family
ID=22846564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19631468283 Granted DE1468283A1 (en) | 1962-09-24 | 1963-09-17 | Dibenzocycloheptenes and process for their preparation |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US3306934A (en) |
| AT (1) | AT260203B (en) |
| CH (2) | CH456578A (en) |
| DE (1) | DE1468283A1 (en) |
| DK (1) | DK119354B (en) |
| ES (1) | ES292187A1 (en) |
| FR (1) | FR3193M (en) |
| GB (4) | GB1063524A (en) |
| NL (2) | NL147726B (en) |
| NO (1) | NO115799B (en) |
| SE (2) | SE318271B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3458516A (en) * | 1968-02-16 | 1969-07-29 | American Cyanamid Co | 11-(piperazinyl)dibenz(b,f)(1,4)oxazepines and analogous thiazepines |
| US3903301A (en) * | 1973-02-28 | 1975-09-02 | Merck & Co Inc | Methods of treating muscular disorders |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2686202A (en) * | 1951-03-19 | 1954-08-10 | Pennsylvania Salt Mfg Co | Production of aromatic sulfonyl fluorides |
| US2726265A (en) * | 1954-05-27 | 1955-12-06 | Du Pont | N-2-hydroxy-1-(p-sulfamylbenzoyl) ethylacylamides |
| FR1212723A (en) * | 1958-01-09 | 1960-03-25 | Rhone Poulenc Sa | New carbamoylpiperazine chain phenothiazine derivatives and their preparation |
| US3055890A (en) * | 1958-01-24 | 1962-09-25 | Rhone Poulenc Sa | Phenthiazine derivatives |
| NL240007A (en) * | 1958-06-10 | |||
| US3073847A (en) * | 1959-02-12 | 1963-01-15 | Hoffmann La Roche | 9-(3-amino-1-propynyl) derivatives of 9-xanthenols and 9-thioxanthenols and a process for their preparation |
| NL108955C (en) * | 1959-05-08 | |||
| US3082210A (en) * | 1959-10-29 | 1963-03-19 | Rhone Poulenc Sa | New 10-(azetidinyl-alkyl)phenthiazines |
-
0
- NL NL298304D patent/NL298304A/xx unknown
-
1962
- 1962-09-24 US US225864A patent/US3306934A/en not_active Expired - Lifetime
-
1963
- 1963-09-17 DE DE19631468283 patent/DE1468283A1/en active Granted
- 1963-09-18 AT AT751663A patent/AT260203B/en active
- 1963-09-20 GB GB5915/66A patent/GB1063524A/en not_active Expired
- 1963-09-20 GB GB37089/63A patent/GB1063521A/en not_active Expired
- 1963-09-20 GB GB5913/66A patent/GB1063522A/en not_active Expired
- 1963-09-20 GB GB5914/66A patent/GB1063523A/en not_active Expired
- 1963-09-21 NO NO150187A patent/NO115799B/no unknown
- 1963-09-23 DK DK447763AA patent/DK119354B/en unknown
- 1963-09-23 SE SE10372/63A patent/SE318271B/xx unknown
- 1963-09-23 ES ES292187A patent/ES292187A1/en not_active Expired
- 1963-09-24 NL NL63298304A patent/NL147726B/en unknown
- 1963-09-24 CH CH1176163A patent/CH456578A/en unknown
- 1963-09-24 CH CH184767A patent/CH463494A/en unknown
- 1963-12-20 FR FR957991A patent/FR3193M/en active Active
-
1966
- 1966-07-28 SE SE17804/66A patent/SE344588B/xx unknown
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