Synthesis of Benzoxazole‐2‐carboxylate Derivatives: Electronic‐ and Position‐effect of Functional Groups and Computational Modeling of the Selectivity for Oxazole Ring

Kuzu B., Sarı Ö., Erdem S., Algül Ö., Mengeş N.

CHEMISTRYSELECT, vol.6, pp.2529-2538, 2021 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 6
  • Publication Date: 2021
  • Doi Number: 10.1002/slct.202100174
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Page Numbers: pp.2529-2538
  • Van Yüzüncü Yıl University Affiliated: Yes


thtgerIn this study, Mitsunobu reagent, DEAD (diethyl azodicarbox-
ylate) and PPh
, and ethyl-oxalamide derivatives of 2-amino-
phenol were reacted under mild reaction conditions. As a result
of the cyclization reaction, benzoxazole derivatives bearing an
ester group in the C-2 position were obtained in a one-pot
protocol. It was observed that the electron-donating groups at
the C-5 position and the electron-withdrawing groups at the C-
6 position of the benzene ring increased the yield of the cyclic
product. It was found that the cyclization does not occur when
the carboxylic acid group is substituted in the benzene ring.
The cyclization reaction we performed preferred the 5-endo-trig
reaction instead of the 6-exo-trig. This experimental result was
examined in detail with density functional theory (DFT)
calculations as well. A computational exploration is presented
herein that elucidates the detailed mechanism for Huisgen
zwitterion‘s reaction with ethyl-oxalamide derivatives of 2-
aminophenol. Potential alternative mechanisms were modeled
with DFT calculations via CPCM/M06-2X/6-311+ +G(d,p)//
B3LYP/6-31+ G(d,p) level method in tetrahydrofuran to under-
stand shed light on the mechanism. Our computational results
are in good agreement with experimental findings that
benzoxazole derivatives are the sole products in this reaction