1,3,4-Thiadiazol-2-amine → N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

Participants

Reaction Conditions

Reaction Steps

2,4-Dimethoxybenzaldehyde (771 g, 4.64 mol) was added to a suspension of 2-amino-1,3,4-thiadiazole (391.2 g, 3.87 mol) in xylene (5.87 L) and heated to reflux for 18 hours. Dean-Stark apparatus was used to remove the water. The reaction mixture was cooled to 5° C. and diluted with 2-methyltetrahydrofuran (2.93 L). Sodium tetrahydroborate (73.17 g, 1.93 mol) was added as a single portion. Methanol (782.8 mL) was then added slowly over 30 minutes, maintaining the temperature below 15° C. After a further 30 minutes, water (1 L) was added followed by saturated aqueous sodium bicarbonate solution (1 L) and the mixture stirred at ambient temperature for 18 hours. The biphasic mixture was diluted with 2-methyltetrahydrofuran and heated to 43° C. to aid dissolution. The layers were separated and the organic layer washed with water (3 L) before concentrating in vacuo. The resulting solid was slurried in heptanes (2.5 L), homogenised, filtered, washed with tert-butylmethyl ether and dried to afford the title compound (715 g).

Provenance & Evidence