Water → 4-Bromo-2H-1,3-benzoxathiole

To a solution of 17 g dibromomethane and Aliquat 336® in 200 ml toluene is added dropwise a solution of 21 g 3-bromo-2-mercapto phenol [prepared according to the procedure of S. Cabiddu et al., Synthesis, loc. cit.] and A. Bashall and J. Collins, Tetrahed. Lett., loc. cit.] 24 g of 50% sodium hydroxide and 50 ml H2O. The reaction mixture is then heated at reflux for 16 hours and cooled to ambient temperature. The organic phase is separated, washed with 1N sodium hydroxide and water, dried and concentrated under reduced pressure to give an oil. The oil is purified via distillation to give 14 g 4-bromo-1,3-benzoxathiole. The oil is dissolved in 60 ml of tetrahydrofuran under a nitrogen atmosphere, cooled to -70° C. and treated sequentially with 45 ml n-butyllithium (1.6N in hexanes) for 1 hour and excess sulfur dioxide until no further exotherm is noted. The reaction mixture is contacted with 2 ml isopropyl alcohol, concentrated in vacuo and crystallized from ether/tetrahydrofuran to give a solid. The solid is added to 150 ml acetic acid and cooled to 20° C. A slurry of 8.0 g N-chlorosuccinimide in 30 ml acetic acid is added portionwise with cooling to maintain a reaction temperature of 20°-25° C. The reaction mixture is stirred for three hours at room temperature and the solvent is removed under reduced pressure to give an oil which is dissolved in methylene chloride and washed with water. The organic phase is dried, and the solvent removed under reduced pressure to give an oil which is dissolved in 250 ml ether and cooled to 10° C. Excess ammonia (anhy.) is bubbled through the reaction mixture with external cooling. The reaction mixture is washed with water, dried, and concentrated under reduced pressure to give a solid.

1. customprepared
2. customCabiddu et al., Synthesis, loc
3. temperatureThe reaction mixture is then heated
4. temperatureat reflux for 16 hours
5. customThe organic phase is separated
6. washwashed with 1N sodium hydroxide and water
7. customdried
8. concentrationconcentrated under reduced pressure
9. customto give an oil
10. distillationThe oil is purified via distillation

ORD record

ord-95bae7c789464a05bbaa2abbe8d40ac0

Source dataset

uspto-grants-1987_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04659368