DE1072623B - Process for the preparation of basic substituted iminodibenzyls, their salts and quaternary ammonium compounds - Google Patents
Process for the preparation of basic substituted iminodibenzyls, their salts and quaternary ammonium compoundsInfo
- Publication number
- DE1072623B DE1072623B DENDAT1072623D DE1072623DB DE1072623B DE 1072623 B DE1072623 B DE 1072623B DE NDAT1072623 D DENDAT1072623 D DE NDAT1072623D DE 1072623D B DE1072623D B DE 1072623DB DE 1072623 B DE1072623 B DE 1072623B
- Authority
- DE
- Germany
- Prior art keywords
- iminodibenzyls
- salts
- radical
- substituted
- nan
- 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.)
- Pending
Links
- 150000003839 salts Chemical class 0.000 title claims description 9
- 239000011780 sodium chloride Substances 0.000 title claims description 9
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 5
- 229940027983 antiseptics and disinfectants Quaternary ammonium compounds Drugs 0.000 title claims description 3
- 150000003856 quaternary ammonium compounds Chemical class 0.000 title claims description 3
- -1 Iminodibenzylcarboxylic acid Chemical compound 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 3
- 230000000875 corresponding Effects 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 241000251730 Chondrichthyes Species 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 125000004433 nitrogen atoms Chemical group N* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- YCBVGFPBRPUIJI-UHFFFAOYSA-N 1,3-bis(dimethylamino)propan-1-ol Chemical class CN(C)CCC(O)N(C)C YCBVGFPBRPUIJI-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SRTHRWZAMDZJOS-UHFFFAOYSA-N Lithium hydride Chemical compound [H-].[Li+] SRTHRWZAMDZJOS-UHFFFAOYSA-N 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N Sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N Sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N o-xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- SCMRSXYMRBPCRB-UHFFFAOYSA-N 2-chloro-N,N,N',N'-tetramethylpropane-1,3-diamine Chemical compound CN(C)CC(Cl)CN(C)C SCMRSXYMRBPCRB-UHFFFAOYSA-N 0.000 description 1
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-N,N-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 229960005015 Local anesthetics Drugs 0.000 description 1
- 229940083877 Local anesthetics for treatment of hemorrhoids and anal fissures for topical use Drugs 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N Methyl iodide Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N Phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003868 ammonium compounds Chemical class 0.000 description 1
- 230000002921 anti-spasmodic Effects 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229940064003 local anesthetic throat preparations Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 230000003285 pharmacodynamic Effects 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- 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 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000002048 spasmolytic Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
DEUTSCHESGERMAN
Die Erfindung betrifft Verfahren zur Herstellung von basisch substituierten Iminodibenzylen der allgemeinen FormelThe invention relates to processes for the preparation of basic substituted iminodibenzyls of the general formula
(R)2N-A-N(R)2
in der A den dreiwertigen Kohlenwasserstoffrest(R) 2 NAN (R) 2
in the A the trivalent hydrocarbon radical
-CH2-CH-CH2-,-CH 2 -CH-CH 2 -,
an den die Aminogruppen in beliebiger Weise an den drei freien Valenzen gebunden sein können, R ein Wasserstoffatom oder einen niedermolekularen Alkylrest bedeuten und der Rest —N(R)2 gegebenenfalls den Rest eines stickstoffhaltigen Heterocyclus, wie den Pyrrolidino-, Piperidino- oder MorphoHnorest, darstellt und die Benzolringe durch Halogenatome oder niedermolukulare Alkyl- oder niedermolekulare Alkoxyrestemithöchstens 4 Kohlenstoffatomen substituiert sein können, sowie von deren Salzen und quaternären Ammoniumverbindungen,to which the amino groups can be bonded to the three free valences in any way, R is a hydrogen atom or a low molecular weight alkyl radical and the radical —N (R) 2, if appropriate, the radical of a nitrogen-containing heterocycle, such as the pyrrolidino, piperidino or morphoHno radical, represents and the benzene rings can be substituted by halogen atoms or low molecular weight alkyl or low molecular weight alkoxy radicals with a maximum of 4 carbon atoms, as well as their salts and quaternary ammonium compounds,
Wenn A ein asymmetrisches Kohlenstoffatom enthält, betrifft die Erfindung nicht nur die Herstellung der racemischen Verbindungen, sondern auch die Herstellung der optisch aktiven Isomeren.When A contains an asymmetric carbon atom, the invention relates not only to the preparation of the racemic compounds, but also the preparation of the optically active isomers.
Erfindungsgemäß werden entwederAccording to the invention either
a) in an sich bekannter Weise entsprechende am Stickstoffatom umsubstituierte Iminodibenzyle mit Diaminohalogenalkanen der allgemeinen Formela) in a manner known per se, corresponding iminodibenzyls substituted on the nitrogen atom with diaminohaloalkanes the general formula
(R)2N-A-N(R)2,(R) 2 NAN (R) 2 ,
HaiShark
in der Hai ein Halogenatom bedeutet, oder deren Salzen umgesetzt, oderin which Hai means a halogen atom, or their salts are reacted, or
b) Iminodibenzylcarbonsäure-(5)-ester der allgemeinen Formelb) Iminodibenzylcarboxylic acid (5) esters of the general formula
- C XXg C H.- C XXg C H.
Verfahren zur Herstellung
von basisch substituiertenMethod of manufacture
of basic substituted
Iminodibenzylen,Iminodibenzylene,
deren Salzen und quaternärentheir salts and quaternaries
AmmoniumverbindungenAmmonium compounds
Anmelder:Applicant:
Societe des Usines ChimiquesSociete des Usines Chimiques
Rhöne-Poulenc,Rhone-Poulenc,
ParisParis
Vertreter: Dr. F. Zumstein
und Dipl.-Chem. Dr. rer. nat. E. Assmann,
Patentanwälte, München 2, Bräuhausstr. 4Representative: Dr. F. Zumstein
and Dipl.-Chem. Dr. rer. nat. E. Assmann,
Patent Attorneys, Munich 2, Bräuhausstr. 4th
Beanspruchte Priorität:
Frankreich, vom 26. Oktober 1955Claimed priority:
France, October 26, 1955
Paul Gailliot, Paris,Paul Gailliot, Paris,
und Jean Robert, Gentilly, Seine (Frankreich),
sind als Erfinder genannt wordenand Jean Robert, Gentilly, Seine (France),
have been named as inventors
in der die Benzolringe entsprechend substituiert sein können, durchErhitzendecarboxyliertundgegebenenfalls die erhaltenen Basen mit Säuren oder Quaternisierungsmitteln behandelt.in which the benzene rings can be substituted accordingly, decarboxylated by heating and optionally the bases obtained are treated with acids or quaternizing agents.
Die Umsetzung der Iminodibenzyle mit den Diaminohalogenalkanen wird mit oder ohne Lösungsmitteln und gegebenenfalls in Gegenwart von Kondensationsmitteln ausgeführt. Es ist zweckmäßig, als Lösungsmittel aromatische Kohlenwasserstoffe, beispielsweise Toluol oder Xylol, zu verwenden undin Gegenwart von Kondensationsmitteln, vorzugsweise aus der Gruppe der Alkalimetalle und ihrer Derivate, wie Hydriden, Amiden, Hydroxyden, Alkoholaten, Metallalkylen oder -arylen, metallischem Natrium, Natriumamid, Natrium oder Kalium in Pulverform, Lithiumhydrid, Natrium-tert.-butylat, Butyllithium oder Phenyllithium, zu arbeiten. Man arbeitet vorzugsweise bei der Siedetemperatur des Lösungsmittels. Es ist vorteilhaft, das halogenhaltige Diamin in Form der freien Base in Lösung, beispielsweise in Benzol,The implementation of the Iminodibenzyle with the Diaminohalogenalkanen is with or without solvents and optionally carried out in the presence of condensing agents. It is advisable to use aromatic solvents To use hydrocarbons, for example toluene or xylene, and in the presence of condensing agents, preferably from the group of alkali metals and their derivatives, such as hydrides, amides, hydroxides, alcoholates, metal alkyls or aryls, metallic Sodium, sodium amide, sodium or potassium in powder form, lithium hydride, sodium tert-butoxide, butyllithium or phenyllithium to work. It is preferred to work at the boiling point of the solvent. It is advantageous to use the halogen-containing diamine in the form of the free base in solution, for example in benzene,
909708/321909708/321
Toluol oder Xylol, zu verwenden und es dem Gemisch der anderen Reaktionskomponenten, in dem das Iminodibenzyl schon mindestens teilweise in Form seines Alkalisalzes vorliegen kann, zuzusetzen. Die Reaktion kann ebenso mit einem Salz des halogenhaltigen Diamins ausgeführt werden, doch ist es in diesem Falle erforderlich, eine viel größere Menge des Kondensationsmittels zu verwenden, damit die Säure des eingesetzten Salzes neutralisiert wird.Toluene or xylene, and add it to the mixture of the other reaction components in which the iminodibenzyl can already be present at least partially in the form of its alkali salt, to be added. The reaction can can also be carried out with a salt of the halogen-containing diamine, but in this case it is necessary to use a much larger amount of the condensing agent to neutralize the acidity of the salt used will.
Im Verlaufe der Kondensation kann eine Isomerisierung eintreten, und man erhält dann ein Gemisch der beiden Isomeren in wechselnden MengenIsomerization can occur in the course of the condensation enter, and a mixture of the two isomers is then obtained in varying amounts
, C Hn C Hi , C Hn C Hi
CH2- CH — CH2 — N(R)2 CH 2 - CH - CH 2 - N (R) 2
i
A' — N(R)2 i
A '- N (R) 2
undand
CH2-N(R)2 CH 2 -N (R) 2
CH2-N(R)2 CH 2 -N (R) 2
Man kann diese Isomeren beispielsweise durch Kristallisation eines Salzes, wie des Dihydrochloride, aus Alkohol oder durch Chromatographie trennen. Doch ist es nicht unbedingt erforderlich, diese Trennung durchzuführen, dadiebeiden Isomerensehrähnliche pharmakodynamische Eigenschaften besitzen.These isomers can be obtained, for example, by crystallizing a salt, such as dihydrochloride, from alcohol or separate by chromatography. But it is not absolutely necessary to carry out this separation, since both isomers have very similar pharmacodynamic properties.
Die verfahrensgemäß erhaltenen basisch substituierten Iminodibenzyle werden als Ganglienblocker, Lokalanästhetika undinsbesondere als Spasmolytika verwendet.The basic substituted iminodibenzyls obtained according to the process are used as ganglion blockers, local anesthetics and especially used as antispasmodics.
Es hat sich gezeigt, daß beispielsweise das erfindungsgemäß erhaltene 5-[2',3'-Bis-(dimethylamino)-propyl-(l')]-iminodibenzyl-dihydrochlorid dem ähnlich gebauten, aus der deutschen Patentschrift 829167 und Helvetica Chimica Acta, Bd. 37 (1954), S. 472 bis 483, bekannten, durch Umsetzung von Iminodibenzyl mit y-Dimethylaminopropylchlorid hergestenten N-(y-Dimethylaminopropyl)-iminodibenzyl-hydrochlorid hinsichtlich seiner spasmolytischen Wirksamkeit überlegen ist.It has been shown that, for example, the 5- [2 ', 3'-bis (dimethylamino) propyl- (1')] - iminodibenzyl dihydrochloride obtained according to the invention the similarly built, from the German patent specification 829167 and Helvetica Chimica Acta, Vol. 37 (1954), pp. 472 to 483, known by the reaction of iminodibenzyl with γ-dimethylaminopropyl chloride produced N- (γ-dimethylaminopropyl) -iminodibenzyl hydrochloride is superior in terms of its spasmolytic effectiveness.
Die folgenden Beispiele
gemäße Verfahren.The following examples
proper procedures.
3535
4040
erläutern das erfindungs-explain the invention
Man erhitzt eine Mischung aus 6,65 g Iminodibenzyl, 35 ecm Toluol und 1,52 g Natriumamid 1 Stunde unter Stickstoff am Rückfluß. Man gießt dann im Laufe 1 Stunde 53 ecm einer ll,5%igen Lösung von 1,3-Bis-(dimethylamino)-2-chlorpropan in Toluol ein. Nach lOstündigem Erhitzen am Rückfluß kühlt man ab und wäscht mit 60 ecm Wasser. Die Toluollösung wird anschließend nacheinander mit 70, 30, 20 und 20 ecm η-Salzsäure extrahiert. Die vereinigten wäßrigen sauren Lösungen werden mit 25 ecm Äther gewaschen und dann mit 16 ecm Natronlauge (d = 1,33) behandelt. Man extrahiert dreimal mit je 50 ecm Äther, wäscht die vereinigten Ätherextrakte mit 30 ecm Wasser, trocknet über Natriumsulfat, verjagt den Äther auf dem Wasserbad und destilliert im Vakuum. Man erhält so 6,14 g eines Gemisches von 5-[2',3'-Bis-(dimethylamino)-propyl-(1')]-iminodibenzyl und 5-[Bis-l',3/-(dimethylamino)-propyl-(2')]-iminodibenzyl. Durch Lösen dieser Mischung in Isopropanol und Behandlung mit einer Lösung von Salzsäure in Äthanol erhält man das 5-[2',3'-Bis-(dimethylamino) -propyl-(1')]-iminodibenzyl-dihydrocMorid vom F. 230 bis 232° C (Koflerbank).A mixture of 6.65 g of iminodibenzyl, 35 ecm of toluene and 1.52 g of sodium amide is refluxed under nitrogen for 1 hour. 53 ecm of a 1.5% solution of 1,3-bis (dimethylamino) -2-chloropropane in toluene is then poured in over the course of 1 hour. After refluxing for 10 hours, the mixture is cooled and washed with 60 ecm of water. The toluene solution is then extracted successively with 70, 30, 20 and 20 ecm η-hydrochloric acid. The combined aqueous acidic solutions are washed with 25 ml of ether and then treated with 16 ml of sodium hydroxide solution (d = 1.33). It is extracted three times with 50 ecm of ether each time, the combined ether extracts are washed with 30 ecm of water, dried over sodium sulfate, the ether is expelled on the water bath and distilled in vacuo. This gives 6.14 g of a mixture of 5- [2 ', 3'-bis (dimethylamino) propyl- (1')] - iminodibenzyl and 5- [bis-l ', 3 / - (dimethylamino) - propyl- (2 ')] iminodibenzyl. By dissolving this mixture in isopropanol and treating it with a solution of hydrochloric acid in ethanol, 5- [2 ', 3'-bis (dimethylamino) propyl- (1')] - iminodibenzyl dihydrochloride with a melting point of 230 to 232 is obtained ° C (Koflerbank).
Durch Einwirkung von Methyljodid auf die entsprechende Base in Lösung in Aceton erhält man 5-[2',3'-Bis- (dimethylamino) -propyl- (1')] -iminodibenzylmonomethojodid vom F. 182 bis 184°C (Koflerbank).By the action of methyl iodide on the corresponding Base in solution in acetone gives 5- [2 ', 3'-bis (dimethylamino) propyl- (1')] -iminodibenzylmonomethoiodide from 182 to 184 ° C (Koflerbank).
Durch analoge Arbeitsweise erhält man ein Gemisch von 5-[2',3'-Bis-(diäthylamino)-propyl- (1')]-iminodibenzyl und von 5-[l',3'-Bis-(diäthylamino)-propyl-(2')]-iminodibenzyl, wobei das erste Isomere in überwiegender Menge vorliegt.A mixture of 5- [2 ', 3'-bis (diethylamino) propyl- (1')] - iminodibenzyl is obtained by an analogous procedure and of 5- [l ', 3'-bis- (diethylamino) -propyl- (2')] - iminodibenzyl, the first isomer being predominant Amount is present.
Kp.„,17 164 bis 1680C, Ausbeute 67%.Bp. ", 17 164 to 168 0 C, yield 67%.
3,4 g Iminodibenzylcarbonsäure-(5)-l',3'-bis-(dimethylamino)-propyl-(2')-ester vom F. 72° C werden allmählich von 185 auf 25O0C erhitzt, bis die Kohlendioxydentwicklung aufgehört hat, wozu 1 Stunde erforderlich ist. Das erhaltene ölige Produkt wird in Äther gelöst und die Ätherlösung mit verdünnter Salzsäure extrahiert. Nach dem Alkalischmachen mit verdünnter Natronlauge, Extraktion mit Äther und Abdestillieren des Lösungsmittels erhält man 1,7 g eines Gemisches von 5-[2',3'-Bis-(dimethylammo)-propyl-(l')]-iminodibenzyl und 5-[l',3'-Bis-(dimethylamino)-propyl-(27]-iminodibenzyl mit dem genauen azidimetrischen Titer. Man kann durch Zugabe von Salzsäure in Äther zu einer Lösung dieser Basen in Aceton das 5-[2',3'-Bis-(dimethylamino)-propyl-(l')]-iminodibenzyl-dihydrochlorid vom F. 227 bis 229° C erhalten.3.4 g Iminodibenzylcarbonsäure- (5) -l ', 3'-bis- (dimethylamino) propyl (2') - ester, melting at 72 ° C are gradually heated from 185 to 25O 0 C, until the evolution of carbon dioxide ceased has, which takes 1 hour. The oily product obtained is dissolved in ether and the ether solution is extracted with dilute hydrochloric acid. After making alkaline with dilute sodium hydroxide solution, extraction with ether and distilling off the solvent, 1.7 g of a mixture of 5- [2 ', 3'-bis (dimethylammo) -propyl- (l')] - iminodibenzyl and 5- [l ', 3'-Bis- (dimethylamino) -propyl- (27] -iminodibenzyl with the exact azidimetric titer. By adding hydrochloric acid in ether to a solution of these bases in acetone, the 5- [2', 3 ' -Bis- (dimethylamino) -propyl- (l ')] - iminodibenzyl dihydrochloride with a melting point of 227 to 229 ° C.
Der als Ausgangsmaterial verwendete Ester, dessen Pikrat bei 174 bis 175°C schmilzt, kann in an sich bekannter Weise durch Kondensation des l,3-Bis-(dimethylamino)-propanols-(2) mit Iminodibenzylcarbonsäure-(5)-chlorid vom F. 120 bis 121° C hergestellt werden. Letzteres wird seinerseits durch Einwirkung von Phosgen auf Iminodibenzyl erhalten.The ester used as the starting material, the picrate of which melts at 174 to 175 ° C, can in itself known way by condensation of 1,3-bis (dimethylamino) propanols (2) with iminodibenzylcarboxylic acid (5) chloride with a temperature of 120 to 121 ° C. The latter is in turn due to the action of Get phosgene on iminodibenzyl.
Claims (1)
in der A den dreiwertigen Kohlenwasserstoffrest(R) 2 NAN (R) 2
in the A the trivalent hydrocarbon radical
a) in an sich bekannter Weise entsprechende am Stickstoffatom unsubstituierte Iminodibenzyle mit Diaminohalogenalkanen der allgemeinen Formelto which the amino groups can be bonded to the three free valences in any way, R is a hydrogen atom or a low molecular weight alkyl radical and the radical - N (R) 2 optionally represents the radical of a nitrogen-containing heterocycle and the benzene rings by halogen atoms or low molecular weight alkyl or low molecular weight alkoxy radicals can be substituted with a maximum of 4 carbon atoms, as well as their salts and quaternary ammonium compounds, characterized in that either
a) in a manner known per se, corresponding iminodibenzyls unsubstituted on the nitrogen atom with diaminohaloalkanes of the general formula
und gegebenenfalls die erhaltenen Basen mit Säuren oder Quaternisierungsmittehi behandelt.in which the benzene rings can be substituted accordingly, decarboxylated by heating
and optionally treating the bases obtained with acids or quaternizing agents.
Deutsche Patentschrift Nr. 829 167;
Helvetica Chimica Acta, Bd. 37 (1954), S. 472 bis 483.Considered publications:
German Patent No. 829 167;
Helvetica Chimica Acta, 37: 472-483 (1954).
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