Reactions of 2-amino-2-thiazolines with isocyanates and isothiocyanates. Chemical and computational studies on the regioselectivity, adduct rearrangement, and mechanistic pathways

2-Amino-2-thiazoline derivatives bearing alkyl or aryl substituents at exoc yclic nitrogen have been condensed with different isocyanates and isothiocy anates. The addition occurs at ring endocyclic nitrogen in a regiospecific manner to afford kinetic and enthalpy-favored adducts. The unequivocal assi gnment of these structures has been confirmed by X-ray diffraction analyses of several compounds. The endo adducts do not rearrange on heating with th e sole exception of adducts in which the exocyclic nitrogen remains unsubst ituted. Trapping experiments in the presence of other isocyanates or isothi ocyanates produce the formation of new endo adducts by acyl exchange in the reaction mixture. Semiempirical PM3 calculations full corroborate the high er stability of endo or exo adducts depending on the substitution pattern. The formation of adducts is compatible with a stepwise reaction mechanism, for which semiempirical transition structures could be located in the poten tial energy surface, and the global energetics of the process have been det ermined. The formation of the endo adducts proceeds with a smaller activati on barrier.