Metal-Ammonia Reduction and Reductive Alkylation of N-Alkylnaphthalenesulfonamides. A New Route to Substituted Naphthalenes

Conditions have been found for 1,4-reduction of aromatic sulfonamides (conveniently monitored by electrical conductivity), using metals in THF/liquid ammonia on the pre-formed N-lithium salts (BuLi), without concomitant C-S reductive cleavage. The resulting 1,4-dihydro compounds could be alkylated, either in situ (in the case of simple unfunctionalized halides only) or, following isolation, after further N-alkylation and then forming the monoanion, or after forming the dianion of the N-monoalkylated dihydrosulfonamide, generally using as base n-butyllithium (a simple titration procedure). In the former case functionalized electrophiles (bromo esters, chloroformates) could be utilized. The ratio of α -to γ-alkylation was dependent on the method of alkylation, the reaction medium, the nature of the N-alkyl group(s), and whether a monoanion or a dianion served as substrate. γ-Alkylation products could in some cases be further α-substituted. The α-substituted products aromatized, with loss of SO₂ and amine, by heating, whereas γ-substitution products required hydrolysis by aqueous alkali; this greatly facilitated separation where mixtures were formed. Thus, this dihydrosulfonamide route constitutes a novel and nucleophilic route to 1-substituted, 2-substituted, and, notably, 1,3-disubstituted naphthalenes.