C-(β-d-Glucopyranosyl)formamidrazones, formic acid hydrazides and their transformations into 3-(β-d-glucopyranosyl)-5-substituted-1,2,4- triazoles: A synthetic and computational study

Éva Bokor, Attila Fekete, Gergely Varga, Béla Szocs, Katalin Czifrák, István Komáromi, László Somsák

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Synthesis of O-perbenzoylated 3-(β-d-glucopyranosyl)-5-substituted-1, 2,4-triazoles, precursors of potent inhibitors of glycogen phosphorylase, was studied by ring closures of N1-acyl-carboxamidrazone type intermediates. Reactions of C-(β-d-glucopyranosyl)formimidate or C-(β-d-glucopyranosyl)formamidine with acid hydrazides as well as acylation of C-(β-d-glucopyranosyl)formamidrazone by acid chlorides unexpectedly gave the corresponding 1,3,4-oxadiazoles instead of 1,2,4-triazoles. The desired triazoles were obtained in reactions of C-(β-d-glucopyranosyl)formamidine or C-(β-d-glucopyranosyl)formyl chloride with arenecarboxamidrazones, and also in acylations of N1-tosyl-C-(β-d-glucopyranosyl) formamidrazone with acid chlorides. Theoretical calculations (B3LYP and M06-2X DFT with the standard 6-31G(d,p) basis set) on simple model compounds with methyl and phenyl substituents to understand the bifurcation of the ring closure of N1-acyl-carboxamidrazones indicated that in general the reaction led to 1,2,4-triazoles. However, the probability of the 1,3,4-oxadiazole forming pathway was shown to be significantly higher with N1-benzoyl- acetamidrazones, which were closest analogues of the intermediates resulting in C-glucosyl-1,3,4-oxadiazoles. It was thereby demonstrated that the substitution pattern of the N1-acyl-carboxamidrazones played a fundamental role in determining the direction of the ring closing reaction.

Original languageEnglish
Pages (from-to)10391-10404
Number of pages14
JournalTetrahedron
Volume69
Issue number48
DOIs
Publication statusPublished - Dec 2 2013

Keywords

  • 1,2,4-Triazole
  • 1,3,4-Oxadiazole
  • C-Glucopyranosyl derivative
  • DFT calculation
  • N-Acyl-carboxamidrazone
  • Ring closure

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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