Patent GB-821804-A (GB)
Title: Novel basic ethers and salts thereof and a process for the manufacture of same
Filed: 1958-02-05
Abstract: The invention comprises anthraquinones substituted by a (tertiary-amino)-alkoxy group and optionally substituted by an hydroxy group or a further (tertiary-amino)-alkoxy group, their acid-addition salts and quaternary ammonium derivatives, and their preparation by reacting a salt (preformed or formed in situ by addition of a base) of a mono- or di-hydroxy-anthraquinone with a (tertiary-amino)-alkyl halide.  The reaction is preferably effected in an hydrocarbon solvent.  The addition of about one mol. of base and about one mol. of halide to a dihydroxyanthraquinone results in the formation of a mono-hydroxy-mono-[(tertiary-amino)-alkoxy]-anthraquinone, while the use of about two mols. of base and two mols of halide gives a di-[(tertiary-amino)-alkoxy]-anthraquinone.  The first named product may subsequently be reacted with a second mol. of base and of halide to give a di-[(tertiary-amino)-alkoxy] - anthraquinone. In examples: (1) the sodium salt of 1-hydroxyanthraquinone is refluxed with 2-diethylaminoethyl chloride in toluene to give, on working up, 1 - (21 - diethylamino - ethoxy) - anthraquinone; (2), (3), (4) and (6) anthraquinones containing the following substituents are prepared similarly: 1 - (21 - piperidino - ethoxy) -, 1 - (21 - morpholino - ethoxy) -, 1 - (21 - dimethylaminoisopropoxy) - and 1 - (31 - diethylamino - propoxy)-; (5) 1-hydroxy-anthraquinone is refluxed with aqueous KOH in xylene, water being removed, and the resulting solution is refluxed with 3-dimethylamino-propyl chloride in xylene to give, on working up, 1-(31-dimethylaminopropoxy)-anthraquinone; (7) the potassium salt of 1 : 2-dihydroxy-anthraquinone is prepared as in (5) and is refluxed with 2-diethylamino-ethyl chloride in xylene, the resulting filtered solution is extracted with HCl, the acid extract made alkaline with ammonia and the alkaline solution extracted with ether to give, on standing, crystals of 1-hydroxy-2-(21-diethylamino-ethoxy)-anthraquinone and an ether solution which, on working up, yields 1 : 2-bis-(21-diethylamino-ethoxy)-anthraquinone; (8), (9) and (10) 1 : 4 - bis - (21 - diethylamino - ethoxy)-anthraquinone and the corresponding 21-dimethyl-isopropoxy and 31-dimethylaminopropoxy compounds are similarly prepared; (11) the potassium salt of 1 : 5-dihydroxyanthraquinone is heated with 2-diethylamino ethyl chloride to give, on working up, 1 : 5-bis-(21 - diethylamino - ethoxy) - anthraquinone; (12) and (13) the corresponding 31-diethylaminopropoxy and 21-dimethylamino-isopropoxy compounds are prepared by the method of (7); (14), (16) and (17) 1 : 8-bis-(21-diethylamino-ethoxy)-anthraquinone and the corresponding 31-dimethylamino-propoxy and 21-dimethylaminoisopropoxy compounds are prepared as in (7); (15) 1 - hydroxy - 8 - (21 - diethylamino - ethoxy)-anthraquinone is prepared from the monopotassium salt of 1 : 8-dihydroxyanthraquinone and 2-diethylamino ethyl chloride in toluene; (18) 1-hydroxy-4-(21-dimethylamino-isopropoxy)-anthraquinone is prepared by the method of (5); and (19) the product of (9) is isolated as the dihydrobromide.  Hydrochlorides, methobromides and methiodides of many of the products are described and other salt-forming acids and quaternizing agents are also referred to. A list of further (tertiary-amino)-alkoxy substituents is also given.ALSO:Pharmaceutical compositions comprise anthraquinones substituted by a (disubstituted-amino)-alkoxy group and optionally substituted by an hydroxy group or a further (disubstituted-amino)-alkoxy group or their acid-addition salts or quaternary ammonium derivatives in admixture with carriers and/or excipients in the form of tablets, injectables or ointments. Specified acid addition salts are the phosphate, toluene sulphonate, citrate, oxalate and ascorbate.