THIONO COMPOUNDS. 10. STRUCTURES AND REACTIONS OF INTERMEDIATES FROM THE OXIDATION OF PHOSPHOROTHIOATES^1,2

Abstract

Intermediates from the oxidation of phosphorothioates, (RO)₃PS, were studied previously at low temperature using, ³¹P NMR, UV and Raman spectra. Now reported is further information about the structure of intermediates and about their reactions, both of which afford significant clues as to how phosphorothioates may produce adverse biological reactions after they have been oxidized biologically. Mass spectra identified intermediates corresponding to (RO)₃,PS _n with n up to 7 (although presence of some equivalent masses with two oxygens in place of a sulfur atom is possible). HPLC separated unstable intermediates for which UV and MS evidence again was consistent with the structure (RO)₃PS _n . That intermediates can react as nucleophiles is illustrated by reactions with Ellman's Reagent, which produced a maximum of thiolate ion at about the time ³¹P-NMR and UV indicated a maximum of intermediates. A second illustration of nucleophilicity was reaction with N-ethylmaleimide (and other Michael acceptors), which led to thiiranes and thiirane 1-oxides. That the intermediates can react also as electrophiles is illustrated by reactions (followed by UV and ³¹P NMR) with trimethyl phosphite, hydroxyl ion, and water (perhaps to some extent); use of H₂,¹⁸O did not introduce ¹⁸O into phosphate products, but exchange reactions with H₂,¹⁸O did indicate presence of oxygenated species among the intermediates.

Key Words:

• Ellman's Reagent
• N-ethylmaleimide
• ³¹P NMR spectra
• Phosphorothioates
• Thiiranes
• UV spectra