Synthesis, antimalarial activity, and phototoxicity of some benzo(h)quinoline-4-methanols

Nine alpha-dibutylaminomethylbenzo[h]quinoline-4-methanols were synthesized from the corresponding 1-amino-naphthalenes by the following sequence: 1-aminonaphthalene leads to 1H-benz[g]indole-2,3-dione leads to benzo[h]quinoline-4-carboxylic acid leads to acid chloride leads to bromomethyl ketone leads to epoxide leads to benzo[h]quinoline-4-methanol. Several acid chlorides substituted in the 3 position reacted incompletely with ethereal diazomethane but were efficiently converted, without isolation of the intermediates, to the bromomethyl ketones by reaction with ethoxymagnesium diethylmalonate, bromination, hydrolysis, and decarboxylation. Several compounds prepared, especially alpha-dibutylaminomethyl-2-(2',4'-dimethylphenyl)-3-methyl-6-chlorobenzo[h]quinoline-4-methanol, showed significant antimalarial activity against Plasmodium berghei in infected mice but were moderately phototoxic.