DE1052982B - Process for the production of new, spasmolytically effective, basic ethers, their salts or quaternary ammonium compounds - Google Patents
Process for the production of new, spasmolytically effective, basic ethers, their salts or quaternary ammonium compoundsInfo
- Publication number
- DE1052982B DE1052982B DEA27439A DEA0027439A DE1052982B DE 1052982 B DE1052982 B DE 1052982B DE A27439 A DEA27439 A DE A27439A DE A0027439 A DEA0027439 A DE A0027439A DE 1052982 B DE1052982 B DE 1052982B
- Authority
- DE
- Germany
- Prior art keywords
- endomethylene
- mol
- radical
- salts
- quaternary ammonium
- 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 6
- 150000002170 ethers Chemical class 0.000 title claims description 4
- 150000003856 quaternary ammonium compounds Chemical class 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 238000000034 method Methods 0.000 title claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- -1 alkyl radicals Chemical class 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- FHEPZBIUHGLJMP-UHFFFAOYSA-N cyclohexene Chemical compound [CH]1CCCC=C1 FHEPZBIUHGLJMP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical class NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 6
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 5
- 125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 4
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960001789 papaverine Drugs 0.000 description 3
- WNRWEBKEQARBKV-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine Chemical compound ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 2
- RMGFLMXDCGQKPS-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine Chemical compound ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 2
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 2
- ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 230000001078 anti-cholinergic effect Effects 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-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
- 208000005392 Spasm Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- XGZVPYGIUMLWIE-UHFFFAOYSA-N ethyl hypoiodite Chemical compound CCOI XGZVPYGIUMLWIE-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- KPJPHPFMCOKUMW-UHFFFAOYSA-N iodomethane Chemical compound I[CH2] KPJPHPFMCOKUMW-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000956 myotropic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C35/22—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system
- C07C35/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings
- C07C35/28—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings the condensed ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Verfahren zur Herstellung neuer, spasmolytisch wirksamer, basischer Äther, deren Salzen bzw. quaternären Ammoniumverbindungen Es ist bekannt, daß basische Äther der allgemeinen Formel I, in denen ein Benzolring durch den 2,5-Endomethylen-d 3-cyclohexenylrest gemäß der allgemeinen Formel II, in denen R1 und R2 Alkylreste bedeuten, die gegebenenfalls zusammen mit dem Stickstoffatom zu einem heterocyclischen Rest, z. B. einem Pyrrolidin-, Piperidin- oder Morpholinrest, verbunden sein können, ersetzt ist, starke, das Atropin übertreffende anticholinergische Wirkungen besitzen (vgl. die deutsche Patentschrift 955 595). Es wurde nun gefunden, daß Verbindungen der allgemeinen Formel III, in der R., und R, die obige Bedeutung haben, R3 für einen 2,5-Endomethylencyclohexyl- oder einen 2,5-Endomethylen-43-cyclohexenylrest steht, der gegebenenfalls in 6-Stellung durch einen niederen Alkyl rest substituiert sein kann, wobei R4 für Wasserstoff oder einen niederen Alkylrest steht, wenn R3 ein 6-Alkyl-2,5-endomethylen-43-cyclohexenylrest ist, und R4 für Alkyl steht, wenn R3 ein 2,5-Endomethylen-43-cyclohexenylrest ist und X für Wasserstoff oder Halogen steht, überraschenderweise eine weitgehende Änderung des pharmakologischen Wirkspektrums aufweisen. Die Verbindungen der allgemeinen Formel III können gegebenenfalls im Endomethylenring hydriert sein.Process for the production of new, spasmolytically active, basic ethers, their salts or quaternary ammonium compounds It is known that basic ethers of the general formula I, in which a benzene ring is separated by the 2,5-endomethylene-d 3-cyclohexenyl radical according to the general formula II , in which R1 and R2 are alkyl radicals which, optionally together with the nitrogen atom, form a heterocyclic radical, e.g. B. a pyrrolidine, piperidine or morpholine radical, can be connected, is replaced, have strong anticholinergic effects exceeding atropine (cf. German Patent 955 595). It has now been found that compounds of the general formula III, in which R., and R, have the above meaning, R3 stands for a 2,5-endomethylene cyclohexyl or a 2,5-endomethylene-43-cyclohexenyl radical, optionally in 6-position can be substituted by a lower alkyl radical, where R4 is hydrogen or a lower alkyl radical when R3 is a 6-alkyl-2,5-endomethylene-43-cyclohexenyl radical, and R4 is alkyl when R3 is a 2 , 5-endomethylene-43-cyclohexenyl radical and X stands for hydrogen or halogen, surprisingly have an extensive change in the pharmacological spectrum of activity. The compounds of the general formula III can optionally be hydrogenated in the endomethylene ring.
Die neuen Verbindungen können erhalten werden, indem man ein Carbinol der allgemeinen Formel in der R3, R4 und X die vorerwähnte Bedeutung haben, in an sich bekannter Weise mit Verbindungen der allgemeinen Formel in der R1 und R2 die vorerwähnte Bedeutung haben und Hal für ein Halogenatom steht, kondensiert, die erhaltenen Aminoäther oder deren Hydrierungsprodukte in die entsprechenden Salze physiologisch unbedenklicher Säuren überführt bzw. durch Umsetzung zeit Alkylestern, z. B. Alkylhalogeniden oder Dialkylsulfaten, in üblicher Weise quaternisiert.The new compounds can be obtained by making a carbinol of the general formula in which R3, R4 and X have the aforementioned meaning, in a manner known per se with compounds of the general formula in which R1 and R2 have the aforementioned meaning and Hal stands for a halogen atom, condensed, the amino ethers obtained or their hydrogenation products converted into the corresponding salts of physiologically acceptable acids or by reaction time alkyl esters, eg. B. alkyl halides or dialkyl sulfates, quaternized in the usual way.
Die als Ausgangsstoffe verwendeten Carbinole werden aus den entsprechenden Aldehyden bzw. Ketonen durch Grignard-Reaktion in an sich bekannter Weise erhalten.The carbinols used as starting materials are made from the corresponding Aldehydes or ketones obtained by Grignard reaction in a manner known per se.
Die therapeutischen Eigenschaften der neuen Verbindungen im Vergleich zu den vorbekannten Verbindungen ergeben sich aus der nachfolgenden Tabelle. Wenn man die Werte- der zu vergleichenden Substanzen prüft, ergibt sich; daB die Substanzen a), b) und.-c) in Bestätigung der- Angaben in der deutschen .Patentschrift 955 595 eine- das Atropin um das 2- bis 3fache übersteigende. Wirkung besitzen, während die Wirkung beim myotropen Krampf nur ein Fünftel bis ein Zehntel -der Wirkung . des Papaverins ausmacht. Es handelt sich dabei somit urn typische Anticholinergica.The therapeutic properties of the new compounds in comparison with the previously known compounds are shown in the table below. If you check the values of the substances to be compared, you get; that the substances a), b) and.-c) in confirmation of the information in the German patent specification 955 595 one which exceeds atropine by 2 to 3 times. Have an effect, while the effect in myotropic spasm is only a fifth to a tenth of the effect. of papaverine. These are therefore typical anticholinergics.
. Im Gegensatz hierzu. zeigen die neuen, von der allgemeinen Formel III abgeleiteten Verbindungen eine ausgeprägte und gesteigerte- Papaverinwirkung. Gegenüber Papaverin ist dieser Effekt um -das 2- bis 8fache, gegenüber den vorbekannten Vergleichssubstanzen im Extremfall um das 80fache gesteigert. Dabei ist die anticholinergische Wirkkomponente ähnlich stark entwickelt wie bei den vorbekannten Vergleichssubstanzen.. In contrast to this. show the new, from the general formula III derived compounds have a pronounced and increased papaverine effect. Compared to papaverine, this effect is 2 to 8 times greater than the previously known ones In extreme cases, comparison substances increased by 80 times. Here is the anticholinergic Active component similarly developed as with the previously known comparison substances.
Die nachfolgenden Beispiele` erläutern die Erfindung. Beispiel l ,B-Dimethylaminoäthyl-(6-methyl-2,5-endomethylend 3-tetrahydrobenzhydryl)-äther Eine Lösung von 53,5 g (0,25 Mol) 6-Methyl-2,5-endomethylen-4 3-tetrahydrobenzhydrol in 250 ml Toluol wird unter Rühren mit 10 g (0,25- Mol) Natriumamid versetzt. Nach 15 Minuten werden 27 g (0,25 Mol) Dimethylaminoäthylchlorid zugegeben und das Gemisch 2'-/2 Stunden zum Sieden erhitzt. Nach dem Erkalten wird es mit Wasser aufgenommen. und der organische Anteil mit verdünnter Salzsäure ausgeschüttelt. Die salzsaure Lösung wird mit Natronlauge alkalisch gemacht und ausgeäthert. Nach dem Trocknen über Natriumsulfat wird der Äther entfernt und der Rückstand im Vakuum fraktioniert destilliert. Kp.o,,, = 132 bis 135°C; Ausbeute 50 bis 60°/o der Theorie; Hydrochlorid: F. = -123 bis 127° C.The following examples explain the invention. Example 1, B-Dimethylaminoethyl- (6-methyl-2,5-endomethylend 3-tetrahydrobenzhydryl) ether A solution of 53.5 g (0.25 mol) of 6-methyl-2,5-endomethylene-4 3-tetrahydrobenzhydrol in 250 ml of toluene is while stirring with 10 g (0.25 mol) of sodium amide are added. After 15 minutes, 27 g (0.25 mol) of dimethylaminoethyl chloride are added added and the mixture heated to boiling for 2 '- / 2 hours. After it has cooled down it was taken up with water. and the organic part extracted with dilute hydrochloric acid. The hydrochloric acid solution is made alkaline with sodium hydroxide solution and extracted with ether. To After drying over sodium sulfate, the ether is removed and the residue is removed in vacuo fractionally distilled. Bp = 132 to 135 ° C; Yield 50 to 60% of theory; Hydrochloride: F. = -123 to 127 ° C.
28,5 g (0,1 Mol) des ß-Dimethylaminoäthyl-(6-methyl-2,5-endomethylen-43-tetrahydrobenzhydryl)-äthers werden in 75 ml Essigsäureäthylester gelöst und mit 14,2 g (0,1 Mol) Methyljodid versetzt. Nach 24.-Stunden werden 250 ml absoluter Äther zugegeben, das ausgefallene Salz abgesaugt und aus Aceton oder Essigsäureäthylester umgelöst. .F. = 175 bis 184°C; Ausbeute: 50 bis 600/, der Theorie.28.5 g (0.1 mol) of ß-dimethylaminoethyl (6-methyl-2,5-endomethylene-43-tetrahydrobenzhydryl) ether are dissolved in 75 ml of ethyl acetate and 14.2 g (0.1 mol) Methyl iodide added. After 24 hours, 250 ml of absolute ether are added, the precipitated salt is filtered off with suction and redissolved from acetone or ethyl acetate. .F. = 175 to 184 ° C; Yield: 50 to 600 /, of theory.
Aus 28,5 g (0,1 Mol) ß-DimethylaminoäthyI-(6-methyl-2,5-endomethylen-43-tetrahydrobenzhydryl)-äther und 15,6 g (0,1 Mol) Äthyljodid wird in analoger Weise das ß - Dimethylaminoäthyl- (6 @methyl -2,5 - endomethylen -43-tetrahydrobenzhydryl)-ätherjodäthylat hergestellt. F. = 118 bis 126°C; Ausbeute: 55 bis 65°/o der Theorie. Beispie12 ß-Diäthylaminoäthyl-(6-methyl-2,5-endomethylen-4 3-tetrahydrobenzhydryl)-äther Aus 53,5 g (0,25 Mol) 6-Methyl-2,5-endomethylen-4 3-tetrahydrobenzhydrol und 34 g (0,25 Mol) Diäthylaminoäthylchlorid erhält man in analoger Weise wie im Beispiel 1 den ß-Diäthylaminoäthyl-(6-methyl-2,5-endomethylen-43-tetrahydrobenzhydryl)-äther. Kp.o,4 = 136 bis 139°C; Ausbeute: 40 bis 50% der Theorie; Hydrochlorid: F. = 82 bis 860C.From 28.5 g (0.1 mol) of β-dimethylaminoethyl (6-methyl-2,5-endomethylene-43-tetrahydrobenzhydryl) ether and 15.6 g (0.1 mol) of ethyl iodide is ß - Dimethylaminoäthyl- (6 @methyl -2,5-endomethylene -43-tetrahydrobenzhydryl) -ether iodoethylate produced. M.p. = 118 to 126 ° C; Yield: 55 to 65% of theory. Example 12 ß-diethylaminoethyl- (6-methyl-2,5-endomethylene-4 3-tetrahydrobenzhydryl) ether From 53.5 g (0.25 mol) of 6-methyl-2,5-endomethylene-4 3-tetrahydrobenzhydrol and 34 g (0.25 mol) of diethylaminoethyl chloride are obtained in in a manner analogous to that in Example 1, the ß-diethylaminoethyl (6-methyl-2,5-endomethylene-43-tetrahydrobenzhydryl) ether. Bp 4 = 136 to 139 ° C; Yield: 40 to 50% of theory; Hydrochloride: m.p. = 82 up to 860C.
Beispiel 3 ß-Piperidinoäthyl-(6-methyl-2,5-endomethylend-tetrahydrobenzhydryl)-äther Aus 53,5 g (0,25 Mol) 6-Methyl-2,5-endomethylen-4 3-tetrahydrobenzhydrol und 37 g (0,25 Mol) Piperidinoäthylchlorid erhält man analog Beispiel l den ß-Piperidinoäthyl- (6 -methyl-2,5 - endomethylen-d 3 - tetrahyd ro -benzhydryl)-äther. Kp.o,$ = 165 bis 169°C; Ausbeute: 45 bis 55 °/o der Theorie; Hydrochlorid: F. = 185 bis 187'C Beispie14 ß-Morpholinoäthyl- (6-methyl-2,5-endomethylen-d 3-tetrahydrobenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 6-Methyl-2,5-endomethylen-43-tetrahydrobenzhydrol und 37,5 g (0,25 Mol) Morpholinoäthylchlorid analog Beispiel 1. Kp. 0,4 = 158 bis 162°C; Ausbeute: 25 bis 35 °/o der Theorie; Hydrochlorid: F. = 209 bis212°C Beispiel 5 ß-Pyrrolidinoäthyl- (6-methyl-2,5-endomethylen=43-tetrahydrobenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 6-Methyl-2,5-endomethylen-43-tetrahydrobenzhydrol und 33,5 g (0,25 Mol) Pyrrolidinoäthylchlorid analog Beispiel 1. Kp.o,s = 144 bis 147°C; Ausbeute: 40 bis 5% der Theorie; Hydrochlorid: F. = 179 bis 184°C. Beispiel 6 ß - Dimethylaminoäthyl - (2,5 - endomethylen - 4 3 - tetrahydro-a-methylbenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 2,5-Endomethylen-43-tetrahydro-a-methylbenzhydrol und 27g (0,25 Mol) Dimethylaminoäthylchlorid analog Beispiel 1. Kp.o,, = 138 bis 142°C; Ausbeute: 20 bis 30 °/o derTheorie; Hydrochlorid: F. =173 bis 174°C, Beispiel? ß - Diäthylaminoäthyl - (2,5 - endomethylen - A3 - tetrahyeo=a=methylbenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 2,5-Endomethylen-43-tetrahydro-a-methylbenzhydrol und 34 g (0,25 Mol) Diäthylaminoäthylchlorid analog Beispiel 1. Kp.o,S = 143 bis 148°C; Ausbeute: 30 bis 40 °/o der Theorie; Hydrochlorid: F. = 130 bis 132°C.Example 3 ß-piperidinoethyl (6-methyl-2,5-endomethylend-tetrahydrobenzhydryl) ether From 53.5 g (0.25 mol) of 6-methyl-2,5-endomethylene-4 3-tetrahydrobenzhydrol and 37 g ( 0.25 mol) of piperidinoethyl chloride is obtained analogously to Example 1, the β-piperidinoethyl- (6-methyl-2,5-endomethylene-d 3-tetrahydro-benzhydryl) -ether. Bp $ = 165 to 169 ° C; Yield: 45 to 55% of theory; Hydrochloride: F. = 185 to 187'C Beispie14 ß-Morpholinoäthyl- (6-methyl-2,5-endomethylene-d 3-tetrahydrobenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 6-methyl 2,5-endomethylene-43-tetrahydrobenzhydrol and 37.5 g (0.25 mol) of morpholinoethyl chloride as in Example 1. Bp. 0.4 = 158 to 162 ° C; Yield: 25 to 35% of theory; Hydrochloride: M.p. = 209 to 212 ° C. Example 5 β-Pyrrolidinoethyl (6-methyl-2,5-endomethylene = 43-tetrahydrobenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 6-methyl-2 , 5-endomethylene-43-tetrahydrobenzhydrol and 33.5 g (0.25 mol) of pyrrolidinoethyl chloride analogous to Example 1. Kp.o, s = 144 to 147 ° C; Yield: 40 to 5% of theory; Hydrochloride: m.p. = 179 to 184 ° C. Example 6 β-Dimethylaminoethyl (2,5 -endomethylene-4 3-tetrahydro-α-methylbenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 2,5-endomethylene-43-tetrahydro-α-methylbenzhydrol and 27g (0.25 mol) of dimethylaminoethyl chloride analogous to Example 1. Kp.o ,, = 138 to 142 ° C; Yield: 20 to 30% of theory; Hydrochloride: F. = 173 to 174 ° C, example? ß - Diethylaminoethyl (2,5 - endomethylene - A3 - tetrahyeo = a = methylbenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 2,5-endomethylene-43-tetrahydro-a-methylbenzhydrol and 34 g (0.25 mol) diethylaminoethyl chloride analogous to Example 1. Kp.o, S = 143 to 148 ° C; Yield: 30 to 40% of theory; Hydrochloride: m.p. = 130 to 132 ° C.
Beispiel 8 '- -- ß-Piperidinöäthyl-(2,5-endomethylen-43-tetrahydroa - methyl - benzhydryl) - äther erhält man aus 53,5 g (0;25 Mol) 2,5-Endömethylen-43-tetrahydro-a-methylbenzhydrol und 37 g (0,25 Mol) Piperidinoäthylchlorid analog Beispiel 1. Kp.o,s = 157 bis 165°C; Ausbeute: 30 bis 40 % der Theorie; Hydrochlorid: F.--=* 178 bis 180°C. . _ Beispiel 9 ß-Morpholinoäthyl-(2,5-endomethylen-d 3-tetrahydroa-methylbenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 2,5-Endomethylen-d 3-tetrahydro-a-methylbenzhydrol und 37,5 g (0,25 Mol) Morpholinoäthylchlorid analog Beispiel 1. Kp.o,$ = 168 bis 172°C, Ausbeute: 10 bis 20°/a der Theorie; Hydrochlorid: F. = 165 bis 167°C.Example 8 '- - ß-Piperidinöäthyl- (2,5-endomethylene-43-tetrahydroa - methyl - benzhydryl) - ether is obtained from 53.5 g (0.25 mol) of 2,5-endomethylene-43-tetrahydryl a-methylbenzhydrol and 37 g (0.25 mol) of piperidinoethyl chloride analogous to Example 1. Kp.o, s = 157 to 165 ° C; Yield: 30 to 40% of theory; Hydrochloride: F .-- = * 178 to 180 ° C. . Example 9 β-morpholinoethyl (2,5-endomethylene-d 3-tetrahydroa-methylbenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 2,5-endomethylene-d 3-tetrahydro-a-methylbenzhydrol and 37.5 g (0.25 mol) of morpholino ethyl chloride analogous to Example 1. Kp.o, $ = 168 to 172 ° C, yield: 10 to 20 ° / a of theory; Hydrochloride: m.p. = 165 to 167 ° C.
Beispiel 10 ß-Pyrrolidinoäthyl- (2,5-endomethylen-d 3-tetrahydroa-methylbenzhydryl)-äther erhält man aus 53,5 g (0,25 Mol) 2,5-Endomethylen-43-tetrahydro-a-methylbenzhydrol und 33,5 g (0,25 Mol) Pyrrolidinoäthylchlorid analog Beispiel 1. Kp.o" = 153 bis 158°C; Ausbeute: 50 bis 60 °% der Theorie; Hydrochlorid: F. = 165 bis 167°C.Example 10 β-pyrrolidinoethyl (2,5-endomethylene-d 3-tetrahydroa-methylbenzhydryl) ether is obtained from 53.5 g (0.25 mol) of 2,5-endomethylene-43-tetrahydro-a-methylbenzhydrol and 33 , 5 g (0.25 mol) of pyrrolidinoethyl chloride analogous to Example 1. Kp.o "= 153 to 158 ° C; Yield: 50 to 60 °% of theory; hydrochloride: mp = 165 to 167 ° C.
Beispiel 11 ß - Dimethylaminoäthyl- (4' -chlor -2,5 - endomethylen -d 3-tetrahydro-a-methylbenzhydryl) -äther erhält man aus 62 g (0,25 Mol) 4'-Chlor-2,5-endomethylen-43-tetrahydroa-methylbenzhydrol und 27 g (0,25 Mol) Dimethylaminoäthylchlorid analog Beispiel 1. Kp.o,2 = 140 bis 145°C; Ausbeute: 35 bis 45°/o der Theorie; Hydrochlorid: F. _ 162 bis 163°C.Example 11 β-Dimethylaminoethyl- (4'-chloro -2,5-endomethylene -d 3-tetrahydro-α-methylbenzhydryl) ether is obtained from 62 g (0.25 mol) of 4'-chloro-2,5-endomethylene -43-tetrahydroa-methylbenzhydrol and 27 g (0.25 mol) of dimethylaminoethyl chloride analogous to Example 1. Kp.o.2 = 140 to 145 ° C; Yield: 35 to 45% of theory; Hydrochloride: m.p. 162 to 163 ° C.
Das jodmethylat erhält man aus 32 g (0,1 Mol) ß-Dimethylaminoäthyl-(4'-chlor-2,5-endomethylen - 4 3-tetrahydro-a-methylbenzhydryl)-äther und 14,2 g (0,1 Mol) Methyljodid analog Beispiel 2. F. = 177 bis 182°C. Ausbeute: 80 bis 90 % der Theorie.The iodomethylate is obtained from 32 g (0.1 mol) of ß-dimethylaminoethyl (4'-chloro-2,5-endomethylene-4 3-tetrahydro-a-methylbenzhydryl) ether and 14.2 g (0.1 mol ) Methyl iodide analogous to Example 2. F. = 177 to 182 ° C. Yield: 80 to 90 % of theory.
Beispiel 12 ß-Dimethylaminoäthyl- (6-methyl-2,5-endomethylen-43-tetrahydro-a-methylbenzhydryl)-äther erhält man aus 57 g (0,25 Mol) 6-Methyl-2,5-endomethylen-d 3-tetrahydroa-methylbenzhydrol und 27 g (0,25 Mol) Dimethylaminoäthylchlorid analog Beispiel 1. Kp.o,4 = 123 bis 135°C; Ausbeute: 15 bis 25°/o der Theorie; Hydrochlorid: F. _ 169 bis 171'C. Example 12 β-Dimethylaminoethyl (6-methyl-2,5-endomethylene-43-tetrahydro-α-methylbenzhydryl) ether is obtained from 57 g (0.25 mol) of 6-methyl-2,5-endomethylene-d 3 tetrahydroa-methylbenzhydrol and 27 g (0.25 mol) of dimethylaminoethyl chloride analogous to Example 1. Kp.o, 4 = 123 to 135 ° C; Yield: 15 to 25% of theory; Hydrochloride: m.p. 169 to 171 ° C.
Beispiel 13 ß-Dimethylaminoäthyl- (6 -methyl-2,5-endomethylenhexahydro-a-methylbenzhydryl)-äther erhält man aus 57,5 g (0,25 Mol) 6-Methyl-2,5-endornethylenhexahydroa-methylbenzhydrol und 27 g (0,25 Mol) Dimethylaminoäthylchlorid analog Beispiel 1. Kp.o,s = 154 bis 158°C; Ausbeute: 35 bis 45°/o der Theorie; Hydrochlorid: F. _ 197 bis 198°C.Example 13 β-Dimethylaminoethyl- (6-methyl-2,5-endomethylene-hexahydro-α-methylbenzhydryl) -ether is obtained from 57.5 g (0.25 mol) of 6-methyl-2,5-endornethylenhexahydroa-methylbenzhydrol and 27 g (0.25 mol) of dimethylaminoethyl chloride analogous to Example 1. Kp.o, s = 154 to 158 ° C; Yield: 35 to 45% of theory; Hydrochloride: mp 197-198 ° C.
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEA27439A DE1052982B (en) | 1957-06-29 | 1957-06-29 | Process for the production of new, spasmolytically effective, basic ethers, their salts or quaternary ammonium compounds |
| CH876163A CH374990A (en) | 1957-06-29 | 1958-06-27 | Process for the production of new, spasmolytic compounds |
| CH6113858A CH371112A (en) | 1957-06-29 | 1958-06-27 | Process for the production of new, spasmolytic compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEA27439A DE1052982B (en) | 1957-06-29 | 1957-06-29 | Process for the production of new, spasmolytically effective, basic ethers, their salts or quaternary ammonium compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1052982B true DE1052982B (en) | 1959-03-19 |
Family
ID=6926391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEA27439A Pending DE1052982B (en) | 1957-06-29 | 1957-06-29 | Process for the production of new, spasmolytically effective, basic ethers, their salts or quaternary ammonium compounds |
Country Status (2)
| Country | Link |
|---|---|
| CH (2) | CH374990A (en) |
| DE (1) | DE1052982B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1108684B (en) * | 1960-01-29 | 1961-06-15 | Boehringer & Soehne Gmbh | Process for the production of new basic ethers |
| DE1152410B (en) * | 1959-04-01 | 1963-08-08 | Koninklijke Pharma Fab Nv | Process for the preparation of dibenzocycloheptane derivatives with spasmolytic and central effects |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE955895C (en) * | 1953-08-05 | 1957-01-10 | Gross Berliner Eisenmoebel Fab | Safety device for the support frame of the headboard of a bed, in particular a hospital bed |
-
1957
- 1957-06-29 DE DEA27439A patent/DE1052982B/en active Pending
-
1958
- 1958-06-27 CH CH876163A patent/CH374990A/en unknown
- 1958-06-27 CH CH6113858A patent/CH371112A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE955895C (en) * | 1953-08-05 | 1957-01-10 | Gross Berliner Eisenmoebel Fab | Safety device for the support frame of the headboard of a bed, in particular a hospital bed |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1152410B (en) * | 1959-04-01 | 1963-08-08 | Koninklijke Pharma Fab Nv | Process for the preparation of dibenzocycloheptane derivatives with spasmolytic and central effects |
| DE1108684B (en) * | 1960-01-29 | 1961-06-15 | Boehringer & Soehne Gmbh | Process for the production of new basic ethers |
Also Published As
| Publication number | Publication date |
|---|---|
| CH371112A (en) | 1963-08-15 |
| CH374990A (en) | 1964-02-15 |
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