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Intermediates Stabilized by Tris(triazolylmethyl)amines in the CuAAC Reaction
Author(s) -
Chen Haoqing,
Cai Chengzhi,
Li Siheng,
Ma Yong,
Luozhong Sijin,
Zhu Zhiling
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700555
Subject(s) - acetylide , alkyne , azide , chemistry , cycloaddition , amine gas treating , reaction rate constant , catalysis , adduct , medicinal chemistry , tris , photochemistry , organic chemistry , kinetics , physics , quantum mechanics , biochemistry
Tris(triazolylmethyl)amine ligands ( TL ) are widely used to accelerate the Cu I ‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction, but its mechanistic role remains unclear. Using electrospray ionization mass spectrometry, we detected for the first time the trinuclear TL ‐Cu I 3 ‐acetylide and the dinuclear TL ‐Cu I 2 ‐acetylide complexes in aqueous solution. The apparent second‐order rate constants of their reaction with an azide were 27 and 783 m −1 ⋅s −1 when the alkyne was tethered to TL . In the catalytic system without the tether, the rate constant increased to >146 m −1 ⋅s −1 for the TL ‐Cu I 3 ‐acetylide, but dropped about 14‐fold to approximately 55 m −1 ⋅s −1 for the TL ‐Cu I 2 ‐acetylide. The results indicated that TL accelerated the reaction by stabilizing the Cu I 2 ‐ and Cu I 3 ‐acetylide and their azide‐adduct intermediates, but this role is largely weakened by excess alkyne and other competing ligands under catalytic conditions.