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A Regioselective Synthesis of 2,4-Disubstituted 2H‑1,2,3-Triazoles by Coupling of N‑Tosylhydrazones and Anhydro-Aldose Tosylhydrazones with 4‑Substituted 1H‑1,2,3-Triazoles - Scope and Limitations

Szakács, Bence ; Kaszás, Tímea ; Juhász-Tóth, Éva ; Cservenyák, Ivett ; Timári, István ; Nilsson, Ulf J. LU orcid ; Varga, Luca A. ; Docsa, Tibor ; Molnár, Viktória and Kulcsár, Andrea Enikő , et al. (2025) In ACS Omega 10(50). p.61370-61399
Abstract
In this paper we present the first investigation of the C–N coupling reaction between N-tosylhydrazones including O-peracylated 2,6-anhydro-aldose tosylhydrazones and 1H-1,2,3-triazoles
under catalyst-free conditions. This transformation is characterized by
relatively mild thermal conditions, high regioselectivity in favor of
2,4-disubstituted 2H-1,2,3-triazoles and broad functional group
tolerance as well as applicability in medicinal chemistry due to the
absence of transition metal residues. Tosylhydrazones of aldehydes
showed better results in terms of yields (20–61%) than those of ketones
(13–16%). From the 1,2,3-triazole side the reactions gave very good
results in... (More)
In this paper we present the first investigation of the C–N coupling reaction between N-tosylhydrazones including O-peracylated 2,6-anhydro-aldose tosylhydrazones and 1H-1,2,3-triazoles
under catalyst-free conditions. This transformation is characterized by
relatively mild thermal conditions, high regioselectivity in favor of
2,4-disubstituted 2H-1,2,3-triazoles and broad functional group
tolerance as well as applicability in medicinal chemistry due to the
absence of transition metal residues. Tosylhydrazones of aldehydes
showed better results in terms of yields (20–61%) than those of ketones
(13–16%). From the 1,2,3-triazole side the reactions gave very good
results in terms of regioselectivity with both electron-withdrawing and
electron-donating groups in the 4-position aromatic substituents, while
benzotriazoles proved unselective. The extension of the reaction to
2,6-anhydro-aldose tosylhydrazones retained the excellent
regioselectivity with high yields, to provide a new synthetic pathway
for 2-glycosylmethyl-4-substituted-2H-1,2,3-triazoles, a novel
type of glycomimetics. The carbohydrate derivatives were evaluated as
potential galectin-1 antagonists and glycogen phosphorylase enzyme
inhibitors. In addition to classical 1H and 13C NMR characterizations, advanced 1H–15N
multiple-bond correlation NMR experiments were also performed on some
glycomimetics to get direct evidence for the regioisomer synthesized. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Omega
volume
10
issue
50
pages
30 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:41476521
  • scopus:105025216463
ISSN
2470-1343
DOI
10.1021/acsomega.5c06151
language
English
LU publication?
yes
additional info
© 2025 The Authors. Published by American Chemical Society.
id
abbafbe1-f262-4bec-b714-259c8db060f7
date added to LUP
2026-01-07 10:23:23
date last changed
2026-01-22 05:30:57
@article{abbafbe1-f262-4bec-b714-259c8db060f7,
  abstract     = {{In this paper we present the first investigation of the C–N coupling reaction between <i>N</i>-tosylhydrazones including <i>O</i>-peracylated 2,6-anhydro-aldose tosylhydrazones and 1<i>H</i>-1,2,3-triazoles<br>
 under catalyst-free conditions. This transformation is characterized by<br>
 relatively mild thermal conditions, high regioselectivity in favor of <br>
2,4-disubstituted 2<i>H</i>-1,2,3-triazoles and broad functional group <br>
tolerance as well as applicability in medicinal chemistry due to the <br>
absence of transition metal residues. Tosylhydrazones of aldehydes <br>
showed better results in terms of yields (20–61%) than those of ketones <br>
(13–16%). From the 1,2,3-triazole side the reactions gave very good <br>
results in terms of regioselectivity with both electron-withdrawing and <br>
electron-donating groups in the 4-position aromatic substituents, while <br>
benzotriazoles proved unselective. The extension of the reaction to <br>
2,6-anhydro-aldose tosylhydrazones retained the excellent <br>
regioselectivity with high yields, to provide a new synthetic pathway <br>
for 2-glycosylmethyl-4-substituted-2<i>H</i>-1,2,3-triazoles, a novel <br>
type of glycomimetics. The carbohydrate derivatives were evaluated as <br>
potential galectin-1 antagonists and glycogen phosphorylase enzyme <br>
inhibitors. In addition to classical <sup>1</sup>H and <sup>13</sup>C NMR characterizations, advanced <sup>1</sup>H–<sup>15</sup>N<br>
 multiple-bond correlation NMR experiments were also performed on some <br>
glycomimetics to get direct evidence for the regioisomer synthesized.}},
  author       = {{Szakács, Bence and Kaszás, Tímea and Juhász-Tóth, Éva and Cservenyák, Ivett and Timári, István and Nilsson, Ulf J. and Varga, Luca A. and Docsa, Tibor and Molnár, Viktória and Kulcsár, Andrea Enikő and Márton, Lili and Ábrahám, Anita and Kiss-Szikszai, Attila and József, János and Juhász, László and Somsák, László and Tóth, Marietta}},
  issn         = {{2470-1343}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{50}},
  pages        = {{61370--61399}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Omega}},
  title        = {{A Regioselective Synthesis of 2,4-Disubstituted 2<i>H</i>‑1,2,3-Triazoles by Coupling of <i>N</i>‑Tosylhydrazones and Anhydro-Aldose Tosylhydrazones with 4‑Substituted 1<i>H</i>‑1,2,3-Triazoles - Scope and Limitations}},
  url          = {{http://dx.doi.org/10.1021/acsomega.5c06151}},
  doi          = {{10.1021/acsomega.5c06151}},
  volume       = {{10}},
  year         = {{2025}},
}