Patent GB-815211-A (GB)
Title: Basic ethers
Inventor: HILTMANN RUDOLPH
Filed: 1957-08-13
Abstract: The invention comprises compounds of the formula <FORM:0815211/IV (b)/1> and acid addition salts of these compounds, wherein R1 is an alkyl radical of 1-4 carbon atoms or a monocyclic aralkyl radical and of R2, R3 and R4, two are hydrogen atoms and the other is an alkenyl group such as allyl, propen-(1)-yl, a - and b -methallyl and crotyl. The compounds may be prepared by introducing the gamma-dimethylaminopropyl radical into an alkenyl-substituted 2-alkoxy- or 2-aralkoxy-phenol, for example by treating the phenol with a reactive ester of gamma-dimethylaminopropanol such as a halide, alkylsulphonate or aryl-sulphonate, suitably in the presence of an acid acceptor; alternatively, the phenolic compound may be treated with a reactive ester of a propanol bearing in the gamma position a substituent convertible to a dimethylamino group, such as halogen atom or a hydroxyl group which is subsequently replaced by a dimethylamino group, or a phthalimido group which is saponified and methylated or a carboxylic acid amide group, which is subjected to Hofmann degradation and methylated.  In a further method, the phenolic compound is treated with a derivative of b -hydroxypropionic acid such as b -chloropropionic amide or dimethylamide or b -chloropropionic nitrile followed by conversion of the amide or nitrile group into a dimethylaminomethylene group, similarly the acrylic acid derivatives may be reacted with the phenol followed by similar conversions.  Also, the phenols may be first converted into gammadimethylaminopropyl carbonates which are then decarboxylated. The compounds are used pharmaceutically as central nervous system depressants.  In examples, (1) by the action of dimethylaminopropyl chloride on the appropriate phenol there are obtained 5-propen-(1)-yl-, 4-allyl-, 6-allyl-, 6-propen-(1)-yl- and 4 - propen - 1 - yl-, 2 - methoxy - g  - dimethyl - aminopropoxy - benzene and 2 - ethoxy - 5 - propen - (1) - yl - g  - dimethylaminopropoxy - benzene; (2) 5 - propen - (1) - yl pyrocatecholmono-methyl ether is treated with gammabromopropyl-phthalimide, the resulting gammaphthalimidopropyl ether of 2-methoxy-5-propenylphenol is decomposed by treatment with hydrazine and the amine obtained is methylated with formaldehyde and formic acid to 1 - (gamma - dimethylaminopropoxy) - 2 - methoxy - 5 - propenyl - benzene; (3) 5 - propenyl - pyrocatechol - 2 - monomethyl ether is treated with 1 : 3-dibromopropane and the resulting 1 - (gamma - bromopropoxy) - 2 - methoxy-5-propenylbenzene is treated with dimethylamine to give the product of (2), and (4) 5 - propenyl - pyrocatechol - 2 - monomethyl ether is treated with phosgene in the presence of dimethylaniline, the 2-methoxy-5-propenyl-1-phenoxycarbonyl chloride obtained is treated with gamma-dimethylamino-propanol and the resulting gamma - dimethylaminopropyl 2-methoxy - 5 - propenyl - 1 - phenyl carbonate (hydrochloride M.Pt. 147 DEG  C.) is heated to give the product of (2).ALSO:Pharmaceutical compositions having action as central nervous system depressants comprise basic ethers of the general formula <FORM:0815211/VI/1> and acid addition salts thereof, wherein R1 is an alkyl radical of 1-4 carbon atoms or a monocyclic aralkyl radical and of R2, R3 and R4, one is an alkenyl radical and the other two are hydrogen atoms (see Group IV (b)), in association with a pharmaceutical carrier.  Specified active compounds include the 4- and 6-allyl derivatives and 4-, 5- and 6-propen-(1)-yl derivatives of 2 - methoxy - g  - dimethylaminopropoxybenzene and 2-ethoxy-5-propen-(1)-ylg  - dimethylaminopropoxybenzene.  An example describes the preparation of tablets comprising the latter compound admixed with conventional excipients.