Synthesis, conformation and Hirshfeld surface analysis of benzoxazole methyl ester as a versatile building block for heterocycles

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Saeed A., Shabir G., HÖKELEK T., Florke U., Erben M. F.

HELIYON, vol.7, no.9, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 7 Issue: 9
  • Publication Date: 2021
  • Doi Number: 10.1016/j.heliyon.2021.e08042
  • Journal Name: HELIYON
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Emerging Sources Citation Index (ESCI), Scopus, CAB Abstracts, Food Science & Technology Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: Molecular structure, benzo[d]oxazole-2(3H)-thione, Hirshfeld surface analysis, Natural bond orbital, INTERMOLECULAR INTERACTIONS, CRYSTAL-STRUCTURES, MODEL ENERGIES, IN-VITRO, INSIGHT, THIOSEMICARBAZIDES, DOCKING
  • Hacettepe University Affiliated: Yes


Solventless cyclocondensation of 2-aminothiophenol with thiourea afforded the benzo[d]oxazole-2-thiol (3a) capable of existing also in the tautomeric form benzo[d]oxazole-2(3H)-thione (3b). Acylation with methyl chloroacetate in dry ethanol in absence of any base or catalyst selectively afforded the S-substituted ester 2(methoxycarbonylmethylthio)benzo[d]oxazole (4a) in preference to the corresponding N-substituted ester N(methoxycarbonylmethyl)thioxobenzoxazole (4b). Quantum chemical calculations were conducted to determine the conformational landscape and NBO population analysis showed the strong electronic delocalization via resonance interactions on the 2-mercaptobenzaxazole group. The anomeric effect and the occurrence of a 1,4S...O intramolecular interactions suggest the relevance of chalcogen bonding in the conformational preference. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H center dot center dot center dot H (33.2%), H center dot center dot center dot O/O center dot center dot center dot H (19.9%) and H center dot center dot center dot C/C center dot center dot center dot H (17.8%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, the C-H center dot center dot center dot O hydrogen-bond energy is 44.8 kJ mol(-1).