Polyhydroxynaphthacenes and their preparation

The invention comprises naphthacene compounds of the formula wherein R2 is hydrogen, carboxamido, or N-(C1-C6 alkyl) carboxamido, R4 is hydrogen or dimethylamino, R5 is hydrogen, R7 is hydrogen, halogen or hydroxy, and R8, R9 and R10 are each hydrogen or hydroxy, and of the formula wherein R2 is carboxamido or N-(C1- 6 alkyl)-carboxamido, R4 is hydrogen, R7, R8, R9 and R10 are as defined above, or tautomers thereof, and of the formula wherein R2 is carboxamido or N-(C1-C6 alkyl) carboxamido, R4 is hydrogen, R1 is hydrogen or C1- 6 alkyl, R7, R8, R9 and R10 are as defined above, or tautomers thereof. The novel compounds may be made by condensation of an appropriately substituted phthalic anhydride with a substituted 1,3-dihydroxynaphthalene under Friedel-Crafts conditions to form either a 6-hydroxynapthacene-5,12-quinone (II) when the dihydroxynapththalene contains a hydroxy or alkoxy group in the 5-position, or a naphthacene-6,11-quinone when there is a hydrogen atom or C1-C6 alkyl group in the 5-position. The naphthacenequinones may be reduced to the corresponding compounds of Formula I, for example with a metal and acid, hydriodic acid, catalytic hydrogenation, metal and alkali, reducing salts, or metal couples. The novel compounds may also be made by condensation of a substituted naphthalene with a substituted 3,5-dihydroxyphthalic anhydride to form the 6-hydroxynaphthacene-5,12-quinone which is then reduced as above. In these preparations, the phthalic acids, esters and halides may be used in place of the anhydrides. The 2-carboxamide group may be introduced after the reduction of the naphthacene-quinone by use of the Gatherman-Koch or Reimer-Tieman procedures to prepare the 2-aldehyde which is converted to the amide via the oxime and nitrile. Alternatively the 2-acetyl derivative may be converted to the amide via the carboxylic acid or ester. Compounds of Formula I in which R4 is dimethylamino or R4 is dimethylamino and R7 is chloro are made (in examples) by treating 6-dimethyltetracycline (or its 7-chloro derivative) with acetic-formic anhydride to give the corresponding 6-demethyl-12a-O-formyltetracycline; the latter is distilled in xylene solution forming 6-demethyl-4a,12a-anhydrotetracycline which is dissolved in butanol and HCl and heated on a steam bath to give the desired product.