Background: Although the exploitation of facile and efficient preparation for S-aryl phosphorothioates
has gained considerable interest, there is still great demand for the development of a direct,
convenient and especially environmentally benign protocol to access various phosphorothioates
under relatively mild conditions. The paper attempts to investigate the application of molecular iodine,
an environmentally friendly reagent in the construction of S-P bond between phosphonates and diaryl
disulfides under metal, base and solvent-free conditions.
Methods: Diaryl disulfide (0.5 mmol), H-phosphonate (2.5 mmol), I2 (0.1 mmol) and 30% H2O2 (0.5
mmol) were taken in a 25 mL two-neck flask under air. The reaction mixture was stirred at 80oC for 12
h. Water (20 mL) was added and then the mixture was extracted with EtOAc (4×10 mL). The extracts
were combined and washed by brine (3×10 mL), dried over MgSO4, filtered, and evaporated, and purified
by chromatography on silica gel to obtain the desired products with ethyl acetate/hexane
(v/v=1:3~1:10). The products were characterized by their spectral and analytical data and compared
with those of the known compounds.
Results: The optimal reaction conditions were screened as follows: 1 equiv of diphenyl disulfide,
5 equiv of H-phosphonate, 10mol% of I2 and 30mol% of H2O2 in air at 80oC. Various H-phosphonates
were employed for coupling with diphenyl disulfide, affording to the corresponding products in 60-
78%. On the other hand, either an electron-donating or an electron-withdrawing group such as methyl,
i-propyl, methoxy, nitro or halogen substituents including fluoro, chloro and bromo was introduced into
the S-aryl phosphorothioates without any problem by employing diaryl disulfides bearing such a group
on the phenyl ring at para or meta position, and the corresponding products were between 48-80%.
Conclusion: A molecular iodine-catalyzed cross-coupling reaction between phosphonates and diaryl disulfides
with H2O2 as oxidant was successful. A series of S-aryl phosphorothioates were afforded under
metal, base and solvent-free conditions.