Patent GB-512560-A (GB)
Abstract: 512,560. Isoquinoline compounds. KULZ, F., and HORNUNG, C. A. Dec. 3, 1937, No. 33546. Convention date, Dec. 22, 1936. [Class 2 (iii)] The esterified or etherified hydroxyl groups of isoquinoline compounds, which in the nitrogen containing nucleus, are hydrogenated, non- hydrogenated or partially hydrogenated, substituted by an exalkyl group or groups and if desired by further groups, e.g. alkyl groups,.and which in only one of the benzene nuclei contain at least two partially or entirely esterified or etherified hydroxyl groups preferably in' the ortho position to one another, are converted into free hydroxyl groups. The products may be employed for therapeutic purposes either as such or in the form of their salts with hydrogen halides, sulphuric acid or organic acids. In examples, (1) 1-(#-phenylethyl)-6, 7,-dihydroxy- 1, 2, 3, 4-tetrahydro isoquinoline is obtained in the form of its hydrobromide by heating the corresponding dimethoxy body with hydrogen bromide in the presence of hydrogen. Hydrogen chloride or iodide, or dilute sulphuric acid or aluminium chloride may be used in place of hydrobromic acid. (2) 1-(#-phenylethyl)-6, 7- dihydroxy-2-ethyl-I, 2, 3, 4-tetrahydroisoquinoline hydrobromide is obtained from the corresponding dimethoxy compound. (3) 1-(#-phenylethyl)-6, 7-dihydroxy-3, 4-dihydroisoquinoline hydrobromide is obtained from the corresponding dimethoxy or diacetoxy body. (4) 1-[#- (31, 41 - dihydroxyphenyl) - ethyl] - isoquinoline hydrobromide is obtained from the corresponding dimethoxy compound. (5) 2-[alpha-methyl- #-(3<1>, 4<1>-dihydrosyphenyl)-ethyl]-1, 2, 3, 4- tetrahydro-isoquinoline hydrobromide is obtained from the corresponding 31-methoxy compound, from the corresponding dimethoxy compound or from the corresponding methylenedioxy compound. (6) 1-(3<1>, 4<1>-dihydroxybenzyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrobromide is obtained from the corresponding diathoxy or alkylenedioxy compounds. The starting materials, some of which are new, may be prepared by interacting isoquinoline compounds with aralkyl halides or aromatic aldehydes or ketones according to the Leackat- Wallach process in the case of N-aralkyl bodies, and by condensing suitable amides with acid condensing agents according to the Bischler- Napieralaki process for the others. The Specification as open to inspection under Sect. 91 includes the use of starting materials which are substituted in the nitrogen containing nucleus by aralkylene groups and if desired by alkylene groups. Products obtained for example according to the process of the invention and which are the nitrogen containing nucleus are not fully hydrogenated may be hydrogenated, e.g. with catalytically activated hydrogen or with metals in the presence of acids or electrolytically. According to examples, (1) the product of example (1) above may also be obtained by hydrogenating the product of example (3) above with gaseous hydrogen in the presence of palladium or platinum ; (2) the product of example (4) above may be hydrogenated to the di- or tetrahydro stage 3 ; 1-(#-phenylethyl)-6, 7-dihydroxyisoquinoline hydrobromide is obtained by heating the corresponding dimethoxy body with hydrobromic acid in presence of hydrogen ; (4) 2- (3<1>, 3<1>-dihydroxybenzyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrobromide is similarly obtained from its dimethoxy derivative ; (5) the product of example (6) above may be obtained by eliminating the benzyl groups from 1-(3<1>, 4<1>- dibenzyloxybenzyl)-3, 4-dihydroisoquinoline and hydrogenating. the product; (6) 1-methyl-2- (gamma-phenylpropyl)-6, 7, 8-trihydroxy-1, 2, 3; 4- tetrahydroisoquinoline hydroidide is obtained from the corresponding trimethoxy body by heating with hydriodic acid and red phosphorus; (7) 1, 3-dimethyl-2-(gamma-phenylpropyl)-6, 7-dihydroxytetrahydroisoquinoline hydroiodide and hydrochloride are similarly obtained from the dimethoxy derivative.; (8) 1, 3-dimethyl-2- (gamma-phenylallyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride is similarly obtained from its dimethoxy derivative. (9) 1-(n-heptyl)-2-(gamma-phenylpropyl-3-methyl-6, 7- dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride is similarly obtained from. its dimethoxy derivative. This subject-matter does not appear in the Specification as accepted.