Hydrochloric Acid → 2-Methoxy-5-(nitromethylthio)thiophene

Participants

Reaction Conditions

Reaction Steps

A hexane/THF solution of lithium diisopropylamide was obtained by adding butyllithium (1.55 M hexane solution, 86.45 ml) to a stirred solution of diisopropylamine (101 g) in THF (100 ml) at -70° C. under an argon atmosphere. After 1 hour at -70° C., a solution of 2-(2-methoxythien-5-ylthio)acetic acid (obtained as described in West German OLS no. 1512272; 10.91 g) was added to the diisopropylamide solution during 20 minutes at -70° C. After 2 hours at this temperature, it was allowed to warm up to -40° C. Isoamyl nitrate (21.2 ml) was then added. The mixture was stirred at -40° C. for 2 hours and then at ambient temperature for 16 hours. The mixture was acidified to pH 2 with 2 M hydrochloric acid and stirred for 1 hour, during which time the intermediate 2-nitro-2-(2-methoxythien-5-ylthio)acetic acid underwent decarboxylation. The mixture was added to water (100 ml) and extracted with ethyl acetate. The combined organic layers were washed first with saturated sodium bicarbonate solution (200 ml) (to remove unreacted acidic starting material) and then with 2 M sodium hydroxide (2×200 ml). The latter washings were acidified to pH 2 with 2 M hydrochloric acid and extracted with ether (2×300 ml). The combined extracts were dried (MgSO4) in the presence of activated charcoal and evaporated. The residual oil was purified by column chromatography on silica (300 g) using 15% v/v ethyl acetate/hexane as eluant to give 2-methoxy-5-(nitromethylthio)thiophene (2.9 g) as an oil; NMR (90 MHz): 3.9 (s,3H), 5.25 (s,2H), 6.1 (d,1H), 7.0 (d,1H).

Provenance & Evidence