Synthesis and Thermal Reactivity of 2,2-Dioxo-3-benzyl-7-trifluoromethyl-1H,3H-pyrrolo[1,2-c]thiazole

WALTER J. PELÁEZ; TERESA M.V.D. PINHO E MELO

Leuven

Simposio; 13th Belgian Organic Synthesis Symposium (BOSS XIII); 2012

13th Belgian Organic Synthesis Symposium (BOSS XIII)

Fluorinated compounds play an important role in medicinal chemistry since fluorine substitution in organic molecules often leads to improved metabolic stability, bioavailability and protein-ligand interactions.1 Among fluorinated compounds, trifluoromethylsubstituted molecules have generated considerable attention. The influence of the CF3 group on the physiological activity is usually concerned with the increasing lipophilicity, leading to the improvement of their in vivo transport characteristics. The high electronegativity of the CF3 group results in a quite different electrondensity distribution and significantly changes the reactivity of the molecules. On the other hand, azafulvenium methide systems 1 are reactive intermediates which can be considered ?higher-order? azomethine ylides. They can be generated by thermal extrusion of sulfur dioxide from the corresponding 2,2-dioxo-1H,3H-pyrrolo[1,2-c]thiazoles and participate in pericyclic reactions.2 Furthermore, it has been demonstrated that 5-(trifluoromethyl)azafulvenium methides can be used for the construction of trifluoromethylpyrrole derivatives.