Syntheses of 3,6-Dimethylcholanthrene, 3,6-Dimethyl-7-methoxycholanthrene, and 7-Methoxy-3-methylcholanthrene

Article abstract of DOI:10.1021/jo00190a001

The condensations of 2-lithio-N,N-diethyl-1-naphthamide and 2-lithio-N,N-diethyl-8-methoxy-1-naphthamide with 4-methyl-1-indanone, followed by hydrolysis, afforded 2-(1-hydroxy-4-methylindan-1-yl)-1-naphthoic acid lactone (6) and 2-(1-hydroxy-4-methylindan-1-yl)-8-methoxy-1-naphthoic acid lactone (6a), respectively.Reduction of 6 followed by esterification yielded methyl 2-(4-methylindan-1-yl)-1-naphthoate (7a) which by reaction with methyllithium in ether-hexamethylphosphoramide yielded methyl 2-(4-methylindan-1-yl)-1-naphthyl ketone (8).Treatment of 8 with hydrogenfluoride yielded 3,6-dimethylcholanthrene (1).Treatment of 8 with 57 percent hydroiodic acid and phosphorus yielded 6,12-dihydro-3,6-dimethylcholanthrene which could readily be oxidized to 3,6-dimethylcholanthrene (1).The lactone 6a was reduced to 2-(4-methylindan-1-yl)-8-methoxy-1-naphthoic acid (9).Treatment of 9 with oxalyl chloride followed by reduction with triethylsilane and trifluoroacetic acid yielded a crude product which contained 2-(4-methylindan-1-yl)-8-methoxy-1-naphthaldehyde since it afforded 7-methoxy-3-methylcholanthrene (3) on treatment with polyphosphoric acid (PPA).Alternately, methyl 2-(4-methylindan-1-yl)-8-methoxy-1-naphthoate gave 7-methoxy-3-methylcholanthrene on treatment with PPA.Treatment of 9 with 57 percent hydroiodic acid as above gave 8-hydroxy-2-(4-methylindan-1-yl)-1-naphthoic acid lactone (11).Treatment of the acid chloride of 9 with dimethylcuprate yielded methyl 2-(4-methylindan-1-yl)-8-methoxy-1-naphthyl ketone (8a), which by HF cyclization afforded 3,6-dimethyl-7-methoxycholanthrene (2).