Patent GB-909357-A (GB)
Title: Naphthalene derivatives
Inventor: STEPHENSON JOHN STUART
Filed: 1960-05-04
Abstract: The invention comprises naphthalene derivatives of the formula I <FORM:0909357/IV (b)/1> (wherein R1 represents a hydrogen atom or a methyl group, R2 represents a branched-chain propyl or butyl group, and the naphthalene nucleus may optionally bear one or more halogen substituents and/or one or more alkyl or alkoxy substituents containing not more than four carbon atoms), their non-toxic, pharmaceutically - acceptable, acid - addition salts, pharmaceutical preparations containing I or a salt thereof and a diluent or carrier, and processes for preparing I by (i) reducing (e.g. with sodium borohydride or aluminium isopropoxide) a 2-naphthacyl halide and reacting the product with an amine NHR1R2, (ii) reacting a 2-naphhthylethylene oxide or 2-halo-1-hydroxy-1-(21-naphthyl)-ethane with NHR1R2, (iii) reducing (e.g. with sodium borohydride or by catalytic hydrogenation) the corresponding N-mono- or di-substituted 2-aminoacetylnaphthalene or an acid-addition salt thereof, (iv) reacting a 2-aminoacetylnaphthalene or 2-amino-1-hydroxy-1-(21-naphthyl)-ethane with isobutyraldehyde, acetone or methyl ethyl ketone under reducing conditions (applicable only when R1 represents a hydrogen atom and R2 represents an isopropyl, isobutyl or sec.-butyl group), and (v) hydrolysing an N-, O- or N,O-acyl derivative of a 2-(branched-chain propyl or butyl)amino - 1 - hydroxy - 1 - (21 - naphthyl)-ethane (applicable only when R1 represents a hydrogen atom).  Acid-addition salts of compounds 1 are prepared by reaction with an inorganic or organic acid, e.g. hydrochloric, hydrobromic, phosphoric, sulphuric, oxalic, lactic, tartaric, acetic, salicylic or citric acid.  Examples describe the preparation of [2-hydroxy-2-(21-naphthyl)-ethyl] - isopropylamine and its hydrochloride and hydrobromide, [2-hydroxy-2-(21-naphthyl)-ethyl]-tert. - butylamine and its oxalate, [2-hydroxy-2-(21-naphthyl)-ethyl] - sec. - butylamine hydrochloride, [2-hydroxy - 2 - (21-naphthyl)-ethyl]-isobutylamine hydrochloride, [2 - (61 - ethyl - 21 - naphthyl)-2-hydroxyethyl] - isopropylamine oxalate, [2-hydroxy - 2 - (61-bromo-21-naphthyl)-ethyl]-isopropylamine hydrobromide, [2-(41-bromo-11-methoxy - 21 - naphthyl) - 2 - hydroxyethyl]-isopropylamine hydrochloride, [2-(51-bromo-61-methoxy - 21 - naphthyl) - 2 - hydroxyethyl]-isopropylamine, [2 - hydroxy - 2 - (61 - methoxy-21-naphthyl) - ethyl] - isopropylamine and [2-hydroxy-2-(21-naphthyl)-ethyl]-methylisopropylamine hydrochloride. 2-Bromo-1-hydroxy-1-(21-naphthyl)-ethane is prepared by reducing 2-naphthacyl bromide with aluminium isopropoxide in isopropanol.  2 - Bromo-1-(61-ethyl-21-naphthyl)-1-hydroxyethane, 2 - bromo-1-(41-bromo-11-methoxy-21-naphthyl) - 1 - hydroxyethane, 2 - bromo-1-(51-bromo - 61 - methoxy-21-naphthyl)-1-hydroxyethane and 2-chloro-1-(61-methoxy-21-naphthyl)-1-hydroxyethane are prepared by reducing the corresponding 2-naphthacyl halide with sodium borohydride in methanol.  2-Naphthylethylene oxide is prepared by treating 2-bromo - 1 - hydroxy-1-(21-naphthyl)-ethane with ethanolic potassium hydroxide solution.  N - [2-Hydroxy-2-(21-naphthyl)-ethyl]-phthalimide is prepared by condensing 1-bromo-2-hydroxy-2-(21-naphthyl)-ethane with potassium phthalimide in dimethylformamide. 2-Hydroxy-2-(21-naphthyl)-ethylamine is prepared by reacting N-[2-hydroxy-2-(21-naphthyl)-ethyl]-phthalimide with hydrazine hydrate in ethanol.  2-Isopropylaminoacetylnaphthalene and 2-methylisopropylaminoacetylnaphthalene oxalates are prepared by condensing 2-naphthacyl bromide with isopropylamine and methylisopropylamine, respectively, followed by treatment with oxalic acid.  According to the first Provisional Specification, R1 in compounds I may represent a hydrogen atom or a hydrocarbon group (e.g. C1-6 alkyl), R2 may represent a hydrocarbon group (e.g. C1-6 alkyl) and the naphthalene nucleus may optionally bear additional substituents.  The compounds I antagonise certain effects of adrenaline on heart muscle and may be administered in the form of pharmaceutical preparations (e.g. tablets, capsules, aqueous or oily solutions, aqueous or oily suspensions, emulsions, injectable aqueous or oily solutions or suspensions and dispersible powders) containing one or more compounds I (as the free base or an acid-addition salt) and a diluent or carrier.