摘要 |
Novel compounds of the formula <FORM:1104516/C2/1> (where B is alkylene, alkarylene or arylene; R is C1- 5 alkyl, trihalomethyl-alkyl, cycloalkyl, aralkyl, aryloxy, arylthio, arylthioalkyl, aralkylthio or carboxyalkyl; R1 and R2 are H or C1- 5 alkyl or they may be joined to form a cycloalkyl ring of 5 or 6 nuclear carbon atoms; X is OH, C1- 5 alkoxy, or N(R3)2 where each R3 is H or C1- 5 alkyl; and X1 and X2 are H, halogen or C1- 5 alkyl, with the proviso that when R1 and R2 are both H and B is C1- 5 alkylene, or mononuclear arylene which may be C1- 5 alkyl substituted, R is not C1- 5 alkyl, cycloalkyl, mononuclear aryl-C1- 5 alkyl, mononuclear aryloxy, carboxy-C1- 5 alkyl, mononuclear arylthio, mononuclear arylthio-C1- 5 alkyl or trihalomethyl-C1- 5 alkyl) and salts thereof are prepared (1) for the free acids, by insertion of the group R.C.R1.R2.CO- into compounds of the above formula wherein X is OH not containing this group, by reaction with the appropriate acyl halide in the presence of a Friedel Craft catalyst, or by etherification of the corresponding naphthols already containing the R.C.R1.R2.CO- group and the optional X1 and X2 groups with the appropriate halo-acid ester hal-B-CO2X1 (X1 is a hydrocarbon group) in the presence of a base, and hydrolysing the resulting ester; and (2) for the salts, esters, amides, by standard procedures from the free acids. Products wherein R is aralkyl and R2 is H may also be prepared by insertion of the aralkyl group into a compound containing an R1-CH2-CO-side chain by condensation with an araldehyde followed by hydrogenation of the arylalkenoyl compound thus obtained. Products wherein R is aryloxy, arylthioalkyl or aralkylthio may also be prepared from compounds containing a haloalkanoyl side chain and an appropriate phenol, thiophenol, or aralkylmercaptan in presence of a base. Products containing a 5-alkyl substituent are difficult to prepare by methods (1) and (2) above and are prepared by reaction of a 5-alkanoyloxy-3,4-dihydro-1(2H)-naphthalenone with a Grignard reagent to give a 1-hydroxy-1-alkyl-1,2,3,4-tetrahydro-5-naphthol, etherification of this to the corresponding alkyl (5-hydroxy-5-alkyl-5,6,7,8-tetrahydro-1-naphthyloxy) alkanoate, dehydration to the corresponding alkyl (7,8-dihydro-5-alkyl-1-naphthyloxy) alkanoate, hydrogenation to the corresponding 5,6,7,8-tetrahydro compound, saponification to the free acid, reaction with an alkanoyl halide to yield a 4-alkanoyl-5 - alkyl - 5,6,7,8 - tetrahydro - 1 - naphthyloxy-alkanoic acid esterification and aromatization. A single example describes the preparation of [4 - (2 - methylbutyryl) - 1 - naphthyloxy]-acetic acid. The naphthalene derivatives of the invention, which are stated to be diuretic or saluretic agents, may be made up into pharmaceutical compositions with or without other diuretics. |