DE1211631B - Process for the preparation of basic indene derivatives and their salts - Google Patents
Process for the preparation of basic indene derivatives and their saltsInfo
- Publication number
- DE1211631B DE1211631B DENDAT1211631D DE1211631DA DE1211631B DE 1211631 B DE1211631 B DE 1211631B DE NDAT1211631 D DENDAT1211631 D DE NDAT1211631D DE 1211631D A DE1211631D A DE 1211631DA DE 1211631 B DE1211631 B DE 1211631B
- Authority
- DE
- Germany
- Prior art keywords
- salts
- basic
- preparation
- indene derivatives
- indene
- 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
- 238000000034 method Methods 0.000 title claims description 7
- 125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 title claims 2
- 150000003839 salts Chemical class 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- -1 2- (2-Dimethylaminoethyl) -3- (2-hydroxyphenyl) -indene Chemical compound 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 150000002469 indenes Chemical class 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000001302 tertiary amino group Chemical group 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- GNPPEZGJRSOKRE-UHFFFAOYSA-N 3-(6h-benzo[c][1]benzoxepin-11-ylidene)-n-methylpropan-1-amine;hydrochloride Chemical compound Cl.C1OC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 GNPPEZGJRSOKRE-UHFFFAOYSA-N 0.000 description 1
- MHNSPTUQQIYJOT-UHFFFAOYSA-N 3-(6h-benzo[c][1]benzoxepin-11-ylidene)propyl-dimethylazanium;chloride Chemical compound Cl.C1OC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 MHNSPTUQQIYJOT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical group C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/12—[b,e]-condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
mehl 1 sollen als Arzneimittel oder als Zwischenprodukte zur Herstellung von Arzneimitteln verwendet werden. Sie lassen sich gewünschtenfalls in üblicher Weise durch Behandlung mit anorganischen oder organischen Säuren in ihre Salze überführen.flour 1 should be used as a medicinal product or as an intermediate product for manufacture used by medicines. If desired, they can be made in the usual way Way to convert them into their salts by treatment with inorganic or organic acids.
Beispiel 1 2-(2-Dimethylaminoäthyl)-3-(2-hydroxyphenyl)-inden 15,8 g (0,05 Mol) 11-(3-Dimethylamino-propyliden)-6, 1 1-dihydro-dibenzo [b,e]oxepin - Hydrochlorid (oder die entsprechende Menge Base), 100 mol Eisessig und 35 ml 480/oige Bromwasserstoffsäure werden 3 Stunden zum Sieden erhitzt. Den Kolbeninhalt versetzt man mit einem Gemisch von Ather + Methylenchlorid und fügt anschließend portionsweise gekühlte, verdünnte Natronlauge bis zur alkalischen Reaktion hinzu. Die abgetrennten organischen Anteile werden getrocknet und vom Lösungsmittel befreit. Der Eindampfungsrückstand ergibt bei der Hochvakuumdestillation 9,3 g (das sind 670/0 der Theorie) 2 - (2 - Dimethylaminoäthyl) -3- (2 - hydroxyphenyl)-inden vom Sdp.o ol 165 bis 170°C. Nach Verreiben mit Ather-Ligroin schmilzt die Verbindung bei 118 bis 1200C. Das auf übliche Weise hergestellte Hydrochlorid besitzt einen Schmelzpunkt von 207 bis 209"C (aus Dioxan). Example 1 2- (2-Dimethylaminoethyl) -3- (2-hydroxyphenyl) -indene 15.8 g (0.05 mol) of 11- (3-dimethylamino-propylidene) -6, 11-dihydro-dibenzo [b, e] oxepin - Hydrochloride (or the corresponding amount of base), 100 mol of glacial acetic acid and 35 ml of 480% Hydrobromic acid is heated to boiling for 3 hours. Moved the contents of the flask one with a mixture of ether + methylene chloride and then added in portions add cooled, dilute sodium hydroxide solution until it has an alkaline reaction. The severed ones organic components are dried and freed from the solvent. The evaporation residue results in high vacuum distillation 9.3 g (that is 670/0 of theory) 2 - (2nd - Dimethylaminoethyl) -3- (2-hydroxyphenyl) -indene from bp 165 to 170 ° C. After trituration with ether-ligroin, the compound melts at 118 to 1200C. That Hydrochloride prepared in the usual way has a melting point of 207 to 209 "C (from dioxane).
Beispiel 2 2-(2-Monomethylaminoäthyl)-3-(2.hydroxyphenyl)-inden a) 3,0 g (0,01 Mol) 11-(3-Monomethylamino-propyliden) - 6,11 - dihydro - dibenzo[b,e]oxepin - Hydrochlorid (oder die entsprechende Menge Base), 18 ml Eisessig und 6 ml 480/obige Bromwasserstoffsäure werden 3 Stunden zum Sieden erhitzt und anschließend gemäß Beispiel 1 aufgearbeitet. Ausbeute: 1,4 g (das sind 53°/0 der Theorie) 2-(2-Monomethylaminoäthyl)-3-(2-hydroxyphenyl)-inden vom Sdp.005 170 bis 175"C; Fp. 160 bis 162"C (nach Verreiben mit Ather- Ligroin). Das auf übliche Weise hergestellte Hydrochlorid schmilzt bei 182 bis 184"C (aus Dioxan). b) 10,2 g (0,03 Mol) 1 1-[3-(N-Carbäthoxy-N-methyl) - aminopropyliden] - dibenzo [b, e] oxepin, 60 ml Eisessig und 20 ml 480/obige Bromwasserstoffsäure werden 3 Stunden zum Sieden erhitzt. Man versetzt den Kolbeninhalt mit Eis, alkalisiert mit verdünnter Natronlauge und extrahiert mit Methylenchlorid. Example 2 2- (2-monomethylaminoethyl) -3- (2.hydroxyphenyl) indene a) 3.0 g (0.01 mol) of 11- (3-monomethylamino-propylidene) -6.11-dihydro-dibenzo [b, e] oxepine - Hydrochloride (or the equivalent amount of base), 18 ml of glacial acetic acid and 6 ml of 480 / above Hydrobromic acid is heated to boiling for 3 hours and then according to Example 1 worked up. Yield: 1.4 g (that is 53% of theory) 2- (2-monomethylaminoethyl) -3- (2-hydroxyphenyl) -indene bp 005 170 to 175 "C; mp 160 to 162" C (after trituration with ether-ligroin). The hydrochloride produced in the usual way melts at 182 to 184 "C ( Dioxane). b) 10.2 g (0.03 mol) 1 1- [3- (N-carbethoxy-N-methyl) - aminopropylidene] - dibenzo [b, e] oxepin, 60 ml of glacial acetic acid and 20 ml of 480 / hydrobromic acid above will Heated to the boil for 3 hours. Ice is added to the contents of the flask and the mixture is made alkaline with dilute sodium hydroxide solution and extracted with methylene chloride.
Nach Entfernung des Lösungsmittels verreibt man den Rückstand mit einem Gemisch aus Ather + Methylenchlorid und erhält 5,1 g (das sind 64,50/o der Theorie) 2-(2-Monomethylaminoäthyl)-3-(2-hydroxyphenyl)-inden vom Fp. 155 bis 158"C.After the solvent has been removed, the residue is triturated with a mixture of ether + methylene chloride and receives 5.1 g (that is 64.50 / o der Theory) 2- (2-monomethylaminoethyl) -3- (2-hydroxyphenyl) indene of m.p. 155 to 158 "C.
Patentanspruch: Verfahren zur Herstellung von basischen Inden-Derivaten der allgemeinen Formel in welcher R1 und R2 Wasserstoff, Halogen, einen Trifluormethyl- oder Alkylrest, R3 Wasserstoff oder eine Alkylgruppe und A eine primäre, sekundäre oder tertiäre Aminogruppe bedeuten, und ihren Salzen, dadurch gekennz e i c h n e t, daß man Verbindungen der allgemeinen Formel in welcher R1, R2 und R3 die oben angegebene Bedeutung haben und B eine primäre, sekundäre oder tertiäre Aminogruppe oder einen in diese überführbaren Rest vorstellt, einer sauren hydrolytischen Spaltung unterwirft und die so erhaltenen basischen Inden-Derivate der Formel 1 gewünschtenfalls auf übliche Weise in ihre Salze überführt.Claim: Process for the preparation of basic indene derivatives of the general formula in which R1 and R2 signify hydrogen, halogen, a trifluoromethyl or alkyl radical, R3 signify hydrogen or an alkyl group and A signify a primary, secondary or tertiary amino group, and their salts, characterized in that compounds of the general formula in which R1, R2 and R3 have the meaning given above and B represents a primary, secondary or tertiary amino group or a radical which can be converted into this, subjecting it to acidic hydrolytic cleavage and the basic indene derivatives of the formula 1 thus obtained, if desired, in the customary manner their salts transferred.
Verfahren zur Herstellung von basischen Inden-Derivaten und ihren Salzen Gegenstand der vorliegenden Patentanmeldung ist ein Verfahren zur Herstellung von neuen Inden-Derivaten der allgemeinen Formel in welcher R1 und R2 Wasserstoff, Halogen, einen Trifluormethyl- oder Alkylrest, R3 Wasserstoff oder eine Alkylgruppe und A eine primäre, sekundäre oder tertiäre Aminogruppe bedeuten.Process for the preparation of basic indene derivatives and their salts The present patent application relates to a process for the preparation of new indene derivatives of the general formula in which R1 and R2 are hydrogen, halogen, a trifluoromethyl or alkyl radical, R3 is hydrogen or an alkyl group and A is a primary, secondary or tertiary amino group.
Es wurde gefunden, daß diese Verbindungen in sehr einfacher und ergiebiger Weise gewonnen werden können, wenn man Verbindungen der allgemeinen Formel in welcher R1, R2 und R3 die oben angegebene Bedeutung haben und B eine primäre, sekundäre oder tertiäre Aminogruppe oder einen in diese überführbaren Rest vorstellt, einer sauren hydrolytischen Spaltung unterwirft. Die Umsetzung wird vorzugsweise durch Verkochung der Verbindungen II mit wäßriger Bromwasserstoffsäure in Eisessig bewirkt.It has been found that these compounds can be obtained in a very simple and productive manner by using compounds of the general formula in which R1, R2 and R3 have the meaning given above and B represents a primary, secondary or tertiary amino group or a radical which can be converted into this, subjecting it to acidic hydrolytic cleavage. The reaction is preferably effected by boiling the compounds II with aqueous hydrobromic acid in glacial acetic acid.
Als in die Aminogruppe überführbare Reste B kommen z. B. folgende Substituenten in Frage: wobei R' eine Carbalkoxy-, Carbaryloxy-, Carbaralkyloxy- oder Cyanogruppe und R" einen Alkyl-, Aralkyl-, Alkenyl- oder Cycloalkylrest bedeutet; unter den Reaktionsbedingungen des erfindungsgemäßen Verfahrens wird R' abhydrolysiert, so daß die entsprechende primäre bzw. sekundäre Aminogruppe entsteht.As radicals B which can be converted into the amino group, for. B. the following substituents in question: where R 'is a carbalkoxy, carbaryloxy, carbaralkyloxy or cyano group and R "is an alkyl, aralkyl, alkenyl or cycloalkyl radical; R' is hydrolyzed under the reaction conditions of the process according to the invention, so that the corresponding primary or secondary amino group arises.
Bei dem erfindungsgemäßen Verfahren handelt es sich um eine neuartige Umlagerungsreaktion, deren Verlauf sehr überraschend ist. Man kann sich zwar vorstellen, daß Verbindungen der Formel II, die eine Benzylätherstruktur (in der Ringgruppierung) aufweisen, gespalten werden und bei der sauren Hydrolyse Verbindungen der Formel III ergeben. The process according to the invention is a novel rearrangement reaction, the course of which is very surprising. One can imagine that compounds of the formula II which have a benzyl ether structure (in the ring grouping) are cleaved and give compounds of the formula III on acid hydrolysis.
Es war aber nicht vorauszusehen, daß unter den angegebenen Reaktionsbedingungen basische Inden-Derivate der allgemeinen Formel 1 entstehen. Besonders überraschend ist die Tatsache, daß diese Umsetzung in guten Ausbeuten und praktisch ohne Nebenreaktionen verläuft. But it could not be foreseen that under the specified reaction conditions basic indene derivatives of the general formula 1 arise. Particularly surprising is the fact that this reaction is in good yields and with practically no side reactions runs.
Die als Ausgangsprodukte benötigten Verbindungen der Formel II nach einem älteren Vorschlag können z. B. durch Grignardierung von 6,1 1-Dihydro-dibenzo[b,ejoxepin-1 1-onen mit den entsprechenden Aminoalkylhalogeniden und anschließende Dehydratisierung erhalten werden. The compounds of the formula II required as starting materials according to an older proposal can e.g. B. by Grignardation of 6,1 1-dihydro-dibenzo [b, ejoxepin-1 1-ones with the corresponding aminoalkyl halides and subsequent dehydration can be obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEB0071910 | 1963-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1211631B true DE1211631B (en) | 1966-03-03 |
Family
ID=6977224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT1211631D Pending DE1211631B (en) | 1963-05-15 | Process for the preparation of basic indene derivatives and their salts |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1211631B (en) |
-
0
- DE DENDAT1211631D patent/DE1211631B/en active Pending
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