4-bromo-2-methylbenzenethiol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the thiocarbamic acid S-ester (34.7 g) in THF (500 mL) under an atmosphere of nitrogen was added a solution of KOH (17.8 g, 2.5 equiv) in MeOH (90 mL), the solution allowed to stir at room temperature for 5 hr and quenched by the addition of 1N HCl, extracted with EtOAc and the organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give 4-bromo-2-methyl benzenethiol which was used immediately. The thiol was added dropwise to a solution of sodium ethoxide (10.3 g, 1.2 equiv) in EtOH (600 mL), allowed to stir for 30 min before the dropwise addition of 2-bromo-1,1-diethoxyethane (23 mL, 1.2 equiv). The reaction mixture was heated at reflux for 4 hr, allowed to cool and stir at room temperature overnight, then quenched by the addition of water and concentrated. Water and EtOAc were added, the phases separated, and the aqueous phase was further extracted with EtOAc. The organic phase was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (SiO2, 5% EtOAC in hexanes) to give 4-bromo-1-(2,2-diethoxyethylsulfanyl)-2-methylbenzene (38.4 g, 88% for 2 steps). The reaction mixture was heated at reflux for 4 hr to cool quenched by the addition of water concentrated Water and EtOAc were added the phases separated the aqueous phase was further extracted with EtOAc The organic phase was dried over Na2SO4 filtered concentrated The crude product was purified by column chromatography (SiO2, 5% EtOAC in hexanes)