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 exocyclic nitrogen have been condensed with different isocyanates and isothiocyanates. The addition occurs at ring endocyclic nitrogen in a regiospecific manner to afford kinetic and enthalpy-favored adducts. The unequivocal assignment of these structures has been confirmed by X-ray diffraction analyses of several compounds. The endo adducts do not rearrange on heating with the sole exception of adducts in which the exocyclic nitrogen remains unsubstituted. Trapping experiments in the presence of other isocyanates or isothiocyanates produce the formation of new endo adducts by acyl exchange in the reaction mixture. Semiempirical PM3 calculations full corroborate the higher 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 potential energy surface, and the global energetics of the process have been determined. The formation of the endo adducts proceeds with a smaller activation barrier.
Avalos
M
M
Departamentos de Química Orgánica y Química Inorgánica, Facultad de Ciencias, Universidad de Extremadura, E-06071 Badajoz, Spain.
Babiano
R
R
Cintas
P
P
Chavero
M M
MM
Higes
F J
FJ
Jiménez
J L
JL
Palacios
J C
JC
Silvero
G
G
D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D017953:Isocyanates / Q000737:chemistry*; D017879:Isothiocyanates / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry*
D007202:Indicators and Reagents; D017953:Isocyanates; D017879:Isothiocyanates; D013844:Thiazoles