Synthesis of stable tetrahedral intermediates (hemiaminals) and kinetics of their conversion to thiazol-2-imines

Gunal S. E. , Gurses G. S. , Erdem S. S. , Dogan I.

TETRAHEDRON, vol.72, no.17, pp.2122-2131, 2016 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 72 Issue: 17
  • Publication Date: 2016
  • Doi Number: 10.1016/j.tet.2016.03.003
  • Title of Journal : TETRAHEDRON
  • Page Numbers: pp.2122-2131


Tetrahedral intermediates (hemiaminals) during thiazol-2-imine formation reactions have been isolated as stable compounds from the LiA1H(4) reduction of the corresponding 2-arylimino-3-aryl-thiazolidine-4-ones and identified by H-1 NMR spectroscopy. In solution, the hemiaminals have been found to slowly convert to the corresponding thiazol-2-imines over time. The first order rate constants for the conversion processes have been determined by time dependent 1H NMR spectroscopic analyses. The half-lives of the hemiaminals were found to be in the range of 2.5-160 days. The hemiaminals owed their ease of formation mainly to the imine conjugation of the amide nitrogen N3, which is expected to increase the electrophilicity of the amide carbonyl by shifting the lone pair of electrons on the amide nitrogen towards the imine side. The stabilities of the hemiaminals were due to the amidine conjugation of the hemiaminal nitrogen and an intramolecular H-bonding interaction for the o-methoxyphenyl derivative as verified by computational studies. The reaction mechanism was investigated by DFT/M06-2X/6-31+G(d,p) method. The computational and experimental data are in agreement with an acid catalyzed water elimination mechanism for the conversion of hemiaminal to thiazol-2-imine. Axial chirality of the hemiaminal 2-o-methoxyphenylimino-3- o-methoxyphenyl-thiazolidine-4-ol, the derivative 2a, was modeled in DMF and in chloroform with DFT/M06-2X/6-31+G(d,p) method. Interestingly, a solvent induced conformational switching between P and M atropisomers has been observed by means of 2D-NOESY and verified by computation, which may provoke future research studies targeting the design of solvent-driven or medium-driven molecular devices as well as chiral reagents. (C) 2016 Elsevier Ltd. All rights reserved.