Supported protic acid-catalyzed synthesis of 2,3-disubstituted thiazolidin-4-ones: enhancement of the catalytic potential of protic acid by adsorption on solid supports

Abstract

The catalytic potential of various protic acids has been assessed for the one pot tandem condensation–cyclisation reaction involving an aldehyde, an amine, and thioglycolic acid to form 2,3-disubstituted thiazolidin-4-ones. The catalytic potential of the various protic acids that follows the order TfOH > HClO₄ > H₂SO₄ ∼ p-TsOH > MsOH ∼ HBF₄ > TFA ∼ AcOH is improved significantly by adsorption on solid supports, in particular using silica gel (230–400 mesh size), with the resulting relative catalytic potential following the order HClO₄–SiO₂ > TfOH–SiO₂ ≫ H₂SO₄–SiO₂ > p-TsOH–SiO₂ > MsOH–SiO₂ ∼ HBF₄–SiO₂ > TFA–SiO₂ ∼ HOAc–SiO₂. The better catalytic potential of HClO₄–SiO₂ as compared to that of Tf–SiO₂, although TfOH is a stronger protic acid than HClO₄, can be rationalised through a transition state model depicting the interaction of the individual protic acid with SiO₂. The catalytic efficiency of HClO₄ adsorbed on various solid supports was in the order HClO₄–SiO₂ ≫ HClO₄–K10 > HClO₄–KSF > HClO₄–TiO₂ ∼ HClO₄–Al₂O₃. The catalytic system HClO₄–SiO₂ is compatible with different variations of aldehydes (aryl/heteroaryl/alkyl/cycloalkyl) and the amines (aryl/heteroaryl/arylalkyl/alkyl/cycloalkyl) affording the desired 2,3-disubstituted thiazolidin-4-ones in 70–87% yields (43 examples). The electronic and the steric factors associated with the aldehydes and the amines provide a handle for selective thiazolidinone formation and were found to be dependent on the extent of imine formation. No significant amount of thiazolidinone formation took place during the reaction of the preformed amide (synthesised from the amine and thioglycolic acid) with benzaldehyde suggesting that the reaction proceeds through the initial reversible imine formation followed by cyclocondensation of the preformed imine with thioglycolic acid, the reversible imine formation being the determining step to control selectivity of thiazolidinone formation in competitive environments. The feasibility of a large scale reaction and catalyst recycling/reuse is demonstrated.