Selective Synthesis of Substituted 3-Aryl-2-phenyl-1,3-thiazolidin-4-one Sulfoxides and Sulfones by S-Oxidation with Oxone

Abstract

S-oxidation of 3-aryl-2-phenyl-1,3-thiazolidin-4-ones with Oxone® was investigated. For all compounds evaluated, selective oxidation to the sulfoxide was realized using 3 equivalents of Oxone® at room temperature. Alternatively, the sulfone was prepared selectively in most of the compounds evaluated at high temperature by increasing the equivalents of Oxone® used; the extent of this selectivity was affected by the substituent and its position on the N3 aromatic ring. The ratio of the sulfoxide and sulfone products was quantified by isolating the products by liquid chromatography.

Selective Synthesis of Ortho-Substituted 2-Aryl-3-phenyl-1,3-thiazolidin-4-one Sulfoxides and Sulfones by S-Oxidation with Oxone®

“…Overall, the total oxidation yields are lower for the 2-aryl-3-phenyl-1,3-thiazolidin-4-ones (average yield = 74%) versus similarly substituted 2-aryl-3-cyclohexyl-1,3-thiazolidin-4-ones (average yield = 91%) despite reactant conversions of 100% for all thiazolidin-4-ones evaluated. In a prior publication, diaryl thiazolidin-4-one sulfones were stable under reaction conditions (8 Oxone ® equivalents in refluxing aqueous methanol for 8 h) as determined by TLC and sulfone recovery (Cannon, et al, 2017). Therefore, product decomposition cannot account for either the lower observed oxidation yields or the relatively higher sulfoxide formation.…”

“…Scheme 1. Oxidation of thiazolidin-4-ones using high temperature Oxone ® -based reaction conditions A subsequent evaluation of S-oxidation of meta-and para-substituted 3-aryl-2-phenyl-1,3-thiazolidin-4-ones with Oxone ® likewise demonstrated selective oxidation to the sulfoxide using 3 equivalents of Oxone ® at room temperature (Cannon, et al, 2017). At high temperature oxidations using 8 equivalents of Oxone ® , the extent of selectivity in sulfone formation was affected by the substituent and its location on the N3 aromatic ring.…”