CH449040A - Process for the production of new araliphatic amines and their salts - Google Patents
Process for the production of new araliphatic amines and their saltsInfo
- Publication number
- CH449040A CH449040A CH1391765A CH1391765A CH449040A CH 449040 A CH449040 A CH 449040A CH 1391765 A CH1391765 A CH 1391765A CH 1391765 A CH1391765 A CH 1391765A CH 449040 A CH449040 A CH 449040A
- Authority
- CH
- Switzerland
- Prior art keywords
- salts
- phenyl
- acid
- new
- araliphatic amines
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 11
- 150000003839 salts Chemical class 0.000 title claims description 10
- 150000001412 amines Chemical class 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 150000007514 bases Chemical class 0.000 claims description 3
- 229950000188 halopropane Drugs 0.000 claims description 3
- -1 hydrocarbon radical Chemical group 0.000 claims description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 2
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 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
- 239000002904 solvent Substances 0.000 description 3
- NVYOCAOZCSNIHR-UHFFFAOYSA-N 2-bromopropylbenzene Chemical compound CC(Br)CC1=CC=CC=C1 NVYOCAOZCSNIHR-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WYTRYIUQUDTGSX-UHFFFAOYSA-N 1-phenylpropan-2-ol Chemical compound CC(O)CC1=CC=CC=C1 WYTRYIUQUDTGSX-UHFFFAOYSA-N 0.000 description 1
- XKCBWDLCZBXXSL-UHFFFAOYSA-N 3,4-diphenylbutan-1-amine Chemical compound C=1C=CC=CC=1C(CCN)CC1=CC=CC=C1 XKCBWDLCZBXXSL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- 239000005711 Benzoic acid Substances 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-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
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 206010047141 Vasodilatation Diseases 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 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
- 230000024883 vasodilation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung von neuen araliphatischen Aminen und deren Salzen
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von neuen araliphatischen Aminen und deren Salzen, die auf das Herz und den Kreislauf wirken.
Es wurde gefunden, dass man araliphatische Amine der Formel I
EMI1.1
worin R1 ein Wasserstoff-oder Halogenatom, R2 einen gegebenenfalls im Phenylkern durch eine niedrig molelculare Alkyl-oder Alkoxygruppe substituierten Benzylrest oder einen Cyclopentyl-bzw. Cyclohexylrest mit 1 oder 2 C-Atomen steht, und deren Salze, erhält, wenn man ein Amin der Formel II
EMI1.2
mit l-Phenyl-2-halogen-propan bzw.-propen umsetzt und eine gegebenenfalls vorhandene Doppelbindung hydriert und gegebenenfalls die erhaltenen basischen Verbindungen mit anorganischen oder organischen Säuren in die entsprechenden Salze überführt.
Als solche l-Phenyl-2-halogen-propane bzw.-pro- pene kommen beispielsweise in Frage : l-Pheny-2-chlor-propan, 1-Phenyl-2-brom-propan oder l-Phenyl-2jod-propan sowie die entsprechenden l-Phenyl-2-halogen-propene. Diese Verbindungen kön- nen durch Halogenierung von Methyl-benzyl-carbinol erhalten werden (vgl. Beilstein Bd. 5, 391 und Bd. 5 I.
Brg. Werk 190).
Diese Umsetzung wird zweckmässig in geeigneten Lösungsmitteln, beispielsweise in aromatischen Kohlenwasserstoffen, wie Benzol oder Toluol, durch länge- res Erhitzen durchgef hrt. Zur Bindung des frei werdenden Halogenwasserstoffes setzt man vorteilhaft 1 Mol 1-Phenyl-2-halogen-propan bzw.-propen mit 2 Molen Amin um. Die Halogenwasserstoffbindung kann auch durch die üblichen basischen Mittel erfolgen, wie Alkali-und Erdalkali-carbonate oder-hydroxyde, sowie organische Basen, wie Pyridin oder Chinolin, die gegebenenfalls gleichzeitig als Lösungsmittel dienen können. Die Aufarbeitung erfolgt in üblicher Weise durch Abtrennung des halogenwasserstoffsauren Salzes der eingesetzten Base, beispielsweise durch Ausfällen mit itther oder Ausschütteln mit Wasser.
Das basische Verfahrensprodukt kann dann durch Destillation oder durch Überführung in ein geeignetes Salz gereinigt werden. Werden Propen-halogenide verwendet, wird die Doppelbindung anschliessend nach den dafür üblichen bekannten Methoden hydriert.
Die Verfahrenserzeugnisse k¯nnen als basische Verbindungen mit Hilfe von anorganischen oder organischen Säuren in die entsprechenden Salze übergeführt werden. Als anorganische Säuren kommen bei- spielsweise in Betracht : Halogenwasserstoffsäuren wie Chlorwasserstoffsäure und Bromwasserstoffsäure sowie SchwefelsÏure, Phosphorsäure und AmidosulfonsÏure.
AIs organische Säuren seien beispielsweise genannt :
Ameisensäure, Essigsäure, Propionsäure, Milch- säure, Glykolsäure, Gluconsäure, Maleinsäure, BernsteinsÏure, WeinsÏure, Benzoesäure, SalicylsÏure, ZitronensÏure, AcetursÏure, OxÏthansulfonsÏure und Athylendiamintetra-Essigsäure. Man kann die Verfah- renserzeugnisse auch mit Hilfe von Alkylhalogeniden in entsprechende quaternäre Salze überführen, wenn der basische Rest ein tertiäres Stickstoffatom enthält.
Die Verfahrensprodukte weisen eine ausserordentlich gute Herz-und Kreislaufwirkung auf. So führt z. B. die Verabreichung von 1-Phenyl-2- [1'-phenyl- l'-cydohexyl-propyl-(3')]-amino-propan im Versuch am isolierten Kaninchenherzen nach Langendorff bei einmaliger Injok : tion von nur 2, 5 y zu einer starken Coronargefässerweiterung, die im Vergleich zu dem normalen unbehandelten Herzen einer Zunahme der Coronardurchströmung von ca. 50 zozo entspricht.
Die Verfahrenserzeugnisse sind den bereits bekann ten Verbindungen ähnlicher Struktur erheblich überlegen, so ist b-ispielsweise von dem bereits bekannten 1-Phenyl-2-[1',1'-diphenyl-propyl-(3')]-amino-propan die Applikation der doppelten Dosis (5 γ) erforderlich, wenn eine gleich starke coronargefässerweiternde Wirkung erreicht werden soll.
Beispiel 22, 5 g 1,2-Diphenyl-4-amino-butan werden mit 10 g 1-Phenyl-2-brom-propan in 150 ccm Toluol 6 Stunden lang unter Rückfluss gekocht. Nach dem Abk hlen versetzt man mit 100 ccm Wasser, trennt die Schichten und destilliert aus der Toluollösung nach Trocknen mit Natrium-sulfat das Lösungsmittel unter vermindertem Druck ab. Der ¯lige R ckstand wird mit 2n-Salzsaure in das Hydrochlorid des 1-Phenyl-2-[1', 2' diphenyl-butyl- (4')]-amino-propans vom Schmelzpunkt 162-l63¯C (¯thanol) berf hrt.
Process for the production of new araliphatic amines and their salts
The invention relates to a process for the preparation of new araliphatic amines and their salts, which act on the heart and circulation.
It has been found that araliphatic amines of the formula I
EMI1.1
wherein R1 is a hydrogen or halogen atom, R2 is a benzyl radical optionally substituted in the phenyl nucleus by a low molecular weight alkyl or alkoxy group or a cyclopentyl or. Cyclohexyl radical with 1 or 2 carbon atoms, and the salts thereof, obtained when an amine of the formula II
EMI1.2
with 1-phenyl-2-halo-propane or -propen and hydrogenated an optionally present double bond and optionally converts the basic compounds obtained with inorganic or organic acids into the corresponding salts.
Examples of such l-phenyl-2-halo-propanes or -propenes are: l-pheny-2-chloro-propane, 1-phenyl-2-bromopropane or l-phenyl-2-iodo-propane and the corresponding l-phenyl-2-halo-propene. These compounds can be obtained by halogenating methyl-benzyl-carbinol (cf. Beilstein Vol. 5, 391 and Vol. 5 I.
Brg. Plant 190).
This reaction is expediently carried out in suitable solvents, for example in aromatic hydrocarbons such as benzene or toluene, by prolonged heating. To bind the liberated hydrogen halide, it is advantageous to react 1 mole of 1-phenyl-2-halo-propane or -propene with 2 moles of amine. The hydrogen halide can also be bonded by the usual basic agents, such as alkali and alkaline earth carbonates or hydroxides, and organic bases, such as pyridine or quinoline, which can optionally also serve as solvents. Working up is carried out in the customary manner by separating off the hydrohalic acid salt of the base used, for example by precipitation with itther or shaking out with water.
The basic process product can then be purified by distillation or by conversion into a suitable salt. If propene halides are used, the double bond is then hydrogenated using the known methods customary for this purpose.
The products of the process can be converted into the corresponding salts as basic compounds with the aid of inorganic or organic acids. Examples of inorganic acids are: hydrohalic acids such as hydrochloric acid and hydrobromic acid, and also sulfuric acid, phosphoric acid and sulfamic acid.
Examples of organic acids are:
Formic acid, acetic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, maleic acid, succinic acid, tartaric acid, benzoic acid, salicylic acid, citric acid, aceturic acid, oxythanesulfonic acid and ethylenediaminetetra-acetic acid. The process products can also be converted into corresponding quaternary salts with the aid of alkyl halides if the basic radical contains a tertiary nitrogen atom.
The products of the process have an extraordinarily good cardiovascular effect. So z. B. the administration of 1-phenyl-2- [1'-phenyl- l'-cydohexyl-propyl- (3 ')] -amino-propane in an experiment on isolated rabbit hearts according to Langendorff with a single injection of only 2.5 y to a strong coronary vasodilatation, which corresponds to an increase of the coronary perfusion of approx. 50 zozo compared to the normal untreated heart.
The products of the process are considerably superior to the already known compounds of a similar structure, for example the application of the already known 1-phenyl-2- [1 ', 1'-diphenyl-propyl- (3')] -amino-propane twice the dose (5?) is required if an equally strong coronary vasodilator effect is to be achieved.
Example 22, 5 g of 1,2-diphenyl-4-aminobutane are refluxed with 10 g of 1-phenyl-2-bromopropane in 150 cc of toluene for 6 hours. After cooling, 100 cc of water are added, the layers are separated and, after drying with sodium sulfate, the solvent is distilled off from the toluene solution under reduced pressure. The oily residue is converted into the hydrochloride of 1-phenyl-2- [1 ', 2' diphenyl-butyl- (4 ')] aminopropane with a melting point of 162-163¯C (¯thanol) with 2N hydrochloric acid transferred.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF32534A DE1181233B (en) | 1960-11-12 | 1960-11-12 | Process for the production of cardiovascular and araliphatic amines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH449040A true CH449040A (en) | 1967-12-31 |
Family
ID=7094673
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1392065A CH449038A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1391865A CH449041A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1391765A CH449040A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1391965A CH449037A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1304861A CH412923A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1392065A CH449038A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1391865A CH449041A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1391965A CH449037A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
| CH1304861A CH412923A (en) | 1960-11-12 | 1961-11-10 | Process for the production of new araliphatic amines and their salts |
Country Status (7)
| Country | Link |
|---|---|
| BE (1) | BE610231A (en) |
| CH (5) | CH449038A (en) |
| DE (1) | DE1181233B (en) |
| FR (1) | FR1753M (en) |
| GB (1) | GB1001827A (en) |
| NL (1) | NL271206A (en) |
| OA (1) | OA01975A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2482956A1 (en) * | 1980-05-22 | 1981-11-27 | Synthelabo | Cardiovascular phenyl or cycloalkyl-cyclohexyl-alkylamine derivs. - which increase coronary flow but not cardiac work e.g. n-alpha-methyl-beta-phenyl:ethyl 2-cyclohexyl 2-phenyl ethylamine |
-
0
- NL NL271206D patent/NL271206A/xx unknown
-
1960
- 1960-11-12 DE DEF32534A patent/DE1181233B/en active Pending
-
1961
- 1961-11-10 CH CH1392065A patent/CH449038A/en unknown
- 1961-11-10 CH CH1391865A patent/CH449041A/en unknown
- 1961-11-10 CH CH1391765A patent/CH449040A/en unknown
- 1961-11-10 CH CH1391965A patent/CH449037A/en unknown
- 1961-11-10 CH CH1304861A patent/CH412923A/en unknown
- 1961-11-13 BE BE610231A patent/BE610231A/en unknown
- 1961-11-13 GB GB40587/61A patent/GB1001827A/en not_active Expired
-
1962
- 1962-02-10 FR FR887649A patent/FR1753M/en active Active
-
1964
- 1964-12-31 OA OA51806A patent/OA01975A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR1753M (en) | 1963-04-01 |
| DE1181233B (en) | 1964-11-12 |
| GB1001827A (en) | 1965-08-18 |
| CH449037A (en) | 1967-12-31 |
| CH449041A (en) | 1967-12-31 |
| OA01975A (en) | 1970-05-05 |
| NL271206A (en) | |
| BE610231A (en) | 1962-05-14 |
| CH412923A (en) | 1966-05-15 |
| CH449038A (en) | 1967-12-31 |
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