AT238160B - Process for the preparation of new dihalo-aminobenzylamines and their acid addition salts with inorganic or organic acids - Google Patents
Process for the preparation of new dihalo-aminobenzylamines and their acid addition salts with inorganic or organic acidsInfo
- Publication number
- AT238160B AT238160B AT917663A AT917663A AT238160B AT 238160 B AT238160 B AT 238160B AT 917663 A AT917663 A AT 917663A AT 917663 A AT917663 A AT 917663A AT 238160 B AT238160 B AT 238160B
- Authority
- AT
- Austria
- Prior art keywords
- sep
- dihalo
- addition salts
- acid addition
- new
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- 239000002253 acid Substances 0.000 title claims description 10
- 150000003839 salts Chemical class 0.000 title claims description 7
- 150000007524 organic acids Chemical class 0.000 title claims description 5
- 235000005985 organic acids Nutrition 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000007522 mineralic acids Chemical class 0.000 title description 4
- -1 alkynyl radical Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 150000003939 benzylamines Chemical class 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- CHRAJVQLWOMYQI-SCZZXKLOSA-N (1s,5r)-5,8,8-trimethyl-3-azabicyclo[3.2.1]octane Chemical group C1NC[C@H]2CC[C@]1(C)C2(C)C CHRAJVQLWOMYQI-SCZZXKLOSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VDQLTWSIHIWIFQ-UHFFFAOYSA-N 5-chloro-2-(3,4-dimethoxyphenyl)-2-propan-2-ylpentanenitrile Chemical compound COC1=CC=C(C(CCCCl)(C#N)C(C)C)C=C1OC VDQLTWSIHIWIFQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- NHOWLEZFTHYCTP-UHFFFAOYSA-N benzylhydrazine Chemical class NNCC1=CC=CC=C1 NHOWLEZFTHYCTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
<Desc/Clms Page number 1>
Verfahren zur Herstellung von neuen Dihalogen-ainino-benzylaminen und deren Säureadditionssalzen mit anorganischen oder organischen Säuren
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen Dihalogen-amino-benzylaminen der Formel
EMI1.1
sowie von deren Säureadditionssalzen mit physiologisch verträglichen anorganischen oder organischen Säuren.
In der obigen Formel I bedeuten Hal ein Chlor- oder Bromatom, R Wasserstoff, geradkettige oder verzweigte niedere Alkyl-, Alkenyl-oder Alkinylreste, Cycloalkyl-, Aralkyl-oder Arylreste, R'gerad- kettige oder verzweigte niedere Alkyl-, Alkenyl-oder Alkinylreste, Cycloalkyl-, Aralkyl- oder Aryl- reste; R und R' können auch zusammen mit dem Stickstoffatom einen gegebenenfalls durch niedere Alkylreste substituierten Pyrrolidin-, Piperidin- oder Camphidinring bedeuten.
Erfindungsgemäss erfolgt die Herstellung der neuen Verbindungen nach für die Synthese halogenierter Amino-benzylamine an sich bekannten Verfahren. Im vorliegenden Falle geschieht dies durch Reduktion von Dihalogen-nitro-benzylaminen der Formel
EMI1.2
in der Hal, R und R'die eingangs erwähnte Bedeutung besitzen.
Die Reaktion wird nach an sich bekannten Verfahren ausgeführt, vorzugsweise durch katalytische Reduktion, beispielsweise mit Wasserstoff in Gegenwart eines Edelmetallkatalysators wie Platin oder Palladium, zweckmässig in einem Lösungsmittel wie Methanol, Äthanol, Tetrahydrofuran oder Dioxan ; durch Reduktion mit Hydrazinhydrat/Raneynickel, vorteilhaft in einem Lösungsmittel wie Methanol, oder durch Reduktion mit naszierendem Wasserstoff, der beispielsweise aus Eisen, Zink oder Zinn und einer Mineralsäure gebildet wird. Die Reduktion kann
<Desc/Clms Page number 2>
aber auch nach allen andern für die Überführung aromatischer Nitroverbindungen in aromatische Aminoverbindungen bekannten Verfahren durchgeführt werden.
Falls nach obigem Verfahren Verbindungen erhalten werden, in denen R Wasserstoff bedeutet, können diese gegebenenfalls nachträglich in Verbindungen überführt werden, in denen R eine der andern eingangs erwähnten Bedeutungen, mit Ausnahme eines Arylrestes, besitzt. Diese Umsetzung erfolgt ebenfalls nach an sich bekannten Methoden, beispielsweise mittels der entsprechenden Alkyl-, Cycloalkyloder Aralkylhalogenide oder-Sulfosäureester ; falls ein Methylrest eingeführt werden soll, kann dies ebenfalls auf bekannte Weise mittels Ameisensäure und Formaldehyd erfolgen.
Die bei dem erfindungsgemässen Verfahren als Ausgangsstoffe verwendeten Verbindungen der Formel II sind aus der Literatur bekannt oder können nach literaturbekannten Verfahren hergestellt werden.
So lassen sich die Dihalogen-nitro-benzylamine der Formel II durch Bromierung der bekannten 2-bzw. 4-Nitro-3, 5-dihalogen-toluole mit Bromsuccinimid und anschliessende Umsetzung der gebildeten Nitrodihalogenbenzylbromide mit dem entsprechenden sekundären Amin erhalten.
Die erfindungsgemäss erhaltenen Verbindungen können mit physiologisch verträglichen anorganischen oder organischen Säuren auf bekannte Weise in ihre Säureadditionssalze überführt werden, beispielsweise durch Umsetzung einer alkoholischen Lösung der betreffenden Säure mit äquimolaren Mengen der entsprechenden Base. Als Säuren haben sich beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Milchsäure, Citronensäure, Weinsäure, Maleinsäure usw. als geeignet erwiesen. Die Säureadditionssalze sind wasserlöslich ; praktische Verwendung finden vor allem die Salze mit einem Äquivalent der betreffenden Säure.
Die erfindungsgemäss hergestellten Verbindungen weisen wertvolle pharmakologische Eigenschaften auf, insbesondere weisen sie eine ausgezeichnete sekretolytische Wirksamkeit bei äusserst geringer Toxizität auf, ausserdem sind sie hustenstillend, monoaminooxydasehemmend und antipyretisch wirksam.
Die nachstehenden Beispiele sollen die Erfindung näher erläutern. Alle Temperaturen sind in Celsiusgraden angegeben.
EMI2.1
l : N-Zers.) werden in 100 ml Methanol gelöst und mit 100 mg PtO versetzt. In diese Lösung wird unter Schütteln Wasserstoff eingeleitet. Nach Aufnahme von 3 Mol Wasserstoff wird vom Katalysator abfiltriert und das Filtrat zur Trockne eingeengt. Nach dem Umkristallisieren aus Äthanol liegt der Schmelzpunkt bei 234 - 235, 50 (Zers.).
Auf die gleiche Weise wurden unter anderem folgende Verbindungen erhalten :
EMI2.2
<tb>
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibrombenzyl)-diäthylamin-hydrochlorid <SEP> F. <SEP> 214 <SEP> - <SEP> 214, <SEP> 50 <SEP>
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibrom-benzyl)-diäthylamin-hydrobromid <SEP> F. <SEP> 2180 <SEP> (Zers.) <SEP>
<tb> N-(2-Amino-3,5-dibrom-benzyl)-diisobutylamin-hydrobromid <SEP> F. <SEP> 165 <SEP> - <SEP> 1670 <SEP>
<tb> N-(2-Amino-3,5-dibrom-benzyl)-diallylamin-hydrochlorid <SEP> F. <SEP> 109 <SEP> - <SEP> 1130 <SEP>
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibrom-benzyl)-diallylamin-hydrocMorid <SEP> F. <SEP> 191 <SEP> - <SEP> 1950 <SEP>
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibNm-benzyl)-N-methyl-benzylaimn-hydrobromid <SEP> F. <SEP> 202-206
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibrom-benzyl)-pyrrolidin-hydrochlorid <SEP> F.
<SEP> 219-220 <SEP>
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibroni-benzyl)-piperidin-hydrochlorid <SEP> F. <SEP> 244-245
<tb> N-(2-Amino-3,5-dichlor-benzyl)-piperidin-hydrochlorid <SEP> F. <SEP> 234 <SEP> - <SEP> 235 <SEP> (Zers.) <SEP>
<tb> N- <SEP> (4-Aniino-3, <SEP> 5-dichlor-benzyl)-N-methyl-cyclohexylamin <SEP> F. <SEP> 62 <SEP> - <SEP> 640 <SEP>
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibiom-benzyl)-isobutylamm-hydrochlorid <SEP> F. <SEP> 211 <SEP> - <SEP> 2130 <SEP> (Zers.) <SEP>
<tb> N-(4-Amino-3,5-dibrom-benzyl)-cyclohexylamin-hydrochlorid <SEP> F. <SEP> 259-2620 <SEP> (Zers.) <SEP>
<tb>
EMI2.3
fend mit Chloroform extrahiert. Die vereinigten Chloroformphasen werden mit Natriumsulfat getrocknet und zur Trockne eingeengt. Die Base wird in 25 ml Äthanol gelöst und mit 2 ml konz. Bromwasserstoffsäure versetzt, wobei das Hydrobromid auskristallisiert.
Nach Umkristallisation aus Äthanol liegt der Schmelzpunkt bei 218, 5-219 (Zers.).
<Desc / Clms Page number 1>
Process for the preparation of new dihalo-amino-benzylamines and their acid addition salts with inorganic or organic acids
The invention relates to a process for the preparation of new dihalogenamino-benzylamines of the formula
EMI1.1
as well as their acid addition salts with physiologically compatible inorganic or organic acids.
In the above formula I, Hal denotes a chlorine or bromine atom, R denotes hydrogen, straight-chain or branched lower alkyl, alkenyl or alkynyl groups, cycloalkyl, aralkyl or aryl groups, R 'straight-chain or branched lower alkyl, alkenyl or Alkynyl residues, cycloalkyl, aralkyl or aryl residues; R and R 'together with the nitrogen atom can also represent a pyrrolidine, piperidine or camphidine ring which is optionally substituted by lower alkyl radicals.
According to the invention, the new compounds are prepared by processes known per se for the synthesis of halogenated aminobenzylamines. In the present case this is done by reducing dihalo-nitro-benzylamines of the formula
EMI1.2
in which Hal, R and R 'have the meaning mentioned at the beginning.
The reaction is carried out according to processes known per se, preferably by catalytic reduction, for example with hydrogen in the presence of a noble metal catalyst such as platinum or palladium, advantageously in a solvent such as methanol, ethanol, tetrahydrofuran or dioxane; by reduction with hydrazine hydrate / Raney nickel, advantageously in a solvent such as methanol, or by reduction with nascent hydrogen, which is formed, for example, from iron, zinc or tin and a mineral acid. The reduction can
<Desc / Clms Page number 2>
but also according to all other processes known for the conversion of aromatic nitro compounds into aromatic amino compounds.
If the above process gives compounds in which R denotes hydrogen, these can optionally be subsequently converted into compounds in which R has one of the other meanings mentioned at the outset, with the exception of an aryl radical. This reaction is also carried out by methods known per se, for example by means of the corresponding alkyl, cycloalkyl or aralkyl halides or sulfonic acid esters; if a methyl radical is to be introduced, this can also be done in a known manner using formic acid and formaldehyde.
The compounds of the formula II used as starting materials in the process according to the invention are known from the literature or can be prepared by processes known from the literature.
Thus, the dihalo-nitro-benzylamines of the formula II can be obtained by bromination of the known 2- or. 4-Nitro-3,5-dihalotoluenes with bromosuccinimide and subsequent reaction of the nitrodihalogenobenzyl bromides formed with the corresponding secondary amine.
The compounds obtained according to the invention can be converted into their acid addition salts using physiologically compatible inorganic or organic acids in a known manner, for example by reacting an alcoholic solution of the acid in question with equimolar amounts of the corresponding base. As the acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid, etc. have proven to be suitable. The acid addition salts are water soluble; In particular, the salts with one equivalent of the acid in question are used in practice.
The compounds prepared according to the invention have valuable pharmacological properties, in particular they have excellent secretolytic activity with extremely low toxicity, and they are also antitussive, monoaminooxidase-inhibiting and antipyretic.
The following examples are intended to explain the invention in more detail. All temperatures are given in degrees Celsius.
EMI2.1
1: N decomposition) are dissolved in 100 ml of methanol and treated with 100 mg of PtO. Hydrogen is passed into this solution with shaking. After 3 mol of hydrogen have been taken up, the catalyst is filtered off and the filtrate is concentrated to dryness. After recrystallization from ethanol, the melting point is 234-235.50 (decomp.).
The following compounds, among others, were obtained in the same way:
EMI2.2
<tb>
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibromobenzyl) diethylamine hydrochloride <SEP> F. <SEP> 214 <SEP> - <SEP> 214, <SEP> 50 <SEP >
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibromobenzyl) diethylamine hydrobromide <SEP> F. <SEP> 2180 <SEP> (decomp.) <SEP>
<tb> N- (2-Amino-3,5-dibromobenzyl) -diisobutylamine-hydrobromide <SEP> F. <SEP> 165 <SEP> - <SEP> 1670 <SEP>
<tb> N- (2-Amino-3,5-dibromobenzyl) -diallylamine hydrochloride <SEP> F. <SEP> 109 <SEP> - <SEP> 1130 <SEP>
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibromobenzyl) -diallylamine-hydrocMorid <SEP> F. <SEP> 191 <SEP> - <SEP> 1950 <SEP>
<tb> N- <SEP> (4-Amino-3, <SEP> 5-dibNm-benzyl) -N-methyl-benzylaimn-hydrobromide <SEP> F. <SEP> 202-206
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibromobenzyl) pyrrolidine hydrochloride <SEP> F.
<SEP> 219-220 <SEP>
<tb> N- <SEP> (2-amino-3, <SEP> 5-dibroni-benzyl) piperidine hydrochloride <SEP> F. <SEP> 244-245
<tb> N- (2-amino-3,5-dichlorobenzyl) -piperidine hydrochloride <SEP> F. <SEP> 234 <SEP> - <SEP> 235 <SEP> (decomp.) <SEP>
<tb> N- <SEP> (4-Aniino-3, <SEP> 5-dichlorobenzyl) -N-methyl-cyclohexylamine <SEP> F. <SEP> 62 <SEP> - <SEP> 640 <SEP>
<tb> N- <SEP> (2-Amino-3, <SEP> 5-dibiom-benzyl) -isobutylamm-hydrochloride <SEP> F. <SEP> 211 <SEP> - <SEP> 2130 <SEP> (dec .) <SEP>
<tb> N- (4-Amino-3,5-dibromobenzyl) cyclohexylamine hydrochloride <SEP> F. <SEP> 259-2620 <SEP> (decomp.) <SEP>
<tb>
EMI2.3
fend extracted with chloroform. The combined chloroform phases are dried with sodium sulfate and evaporated to dryness. The base is dissolved in 25 ml of ethanol and concentrated with 2 ml. Hydrobromic acid is added, the hydrobromide crystallizing out.
After recrystallization from ethanol the melting point is 218.5-219 (decomp.).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE238160X | 1961-11-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT238160B true AT238160B (en) | 1965-01-25 |
Family
ID=5903445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT917663A AT238160B (en) | 1961-11-20 | 1962-11-20 | Process for the preparation of new dihalo-aminobenzylamines and their acid addition salts with inorganic or organic acids |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT238160B (en) |
-
1962
- 1962-11-20 AT AT917663A patent/AT238160B/en active
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