Oxidative cleavage of methylindene (I) by means of Na2Cr2O7 produces 2-acetylphenylacetic acid (II). Fischer esterification of keto acid (II) gives keto ester (III), which is subjected to intramolecular Claisen condensation and air oxidation, yielding the hydroxy naphthoquinone (IV) (1). Alkylation of (IV) with prenyl bromide (V) leads to a mixture of lapachol (VII) and minor amounts of the prenyl ether isomer (VI) (1-3). Finally, cyclization of (VII) in concentrated H2SO4 gives rise to the target compound.
Esterification of 1-naphthol (I) with 3-methylcrotonic acid chloride (II) provides ester (III), which subsequently rearranges to the hydroxy ketone (IV). Cyclization of (IV) under acidic conditions provides the tricyclic system (V). Keto group reduction in (V) by means of LiAlH4 leads to alcohol (VI), which upon acidic treatment is dehydrated to olefin (VII). Further catalytic hydrogenation of (VII) in the presence of Pd/C yields the dihydro naphthopyran (VIII). Electrophilic nitration of (VIII) provides (IX). After reduction of nitro derivative (IX) to the corresponding amine (X) by means of Sn/HCl, acylation with acetic anhydride furnishes acetamide (XI). Finally, oxidation of (XI) with concentrated nitric acid gives rise to the target ortho-quinone .