Chemical aspects of propranolol metabolism: 1,1-diethoxy-3-(1-naphthoxy)-2-propanol and related ring-closure products cis- and trans-4-ethoxy-3-hydroxy-3,4-dihydro-2H-naphtho[1,2-b]pyran.

1,1-Diethoxy-3-(1-naphthoxy)-2-propanol (V), the diethyl acetal of an important aldehyde intermediate in the metabolic N-deal-kylation of propranolol, was prepared from compound X, the product of the reaction of the lithium salt of methyl methylsulfinylmethyl sulfide with 2-(1-naphthoxy)-acetaldehyde. Compound X, as a mixture of three diastereomeric alpha-hydroxydithioacetal derivatives, when treated with ethyl orthoformate afforded the desired acetal V as well as two ring-closure products, the dihydronaphtho[1,2-b]pyrans VI and VII. Compounds VI and VII were characterized on the basis of mass spectral and 1H- and 13C-NMR data. The stereochemistry of these compounds was assigned on the basis of the 300-MHz 1H-NMR spectra of their acetate esters (XI and XII).