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Fig. 2 Azidation of dibenzhydril ether (5a) and benzhydril trimethylsilyl
1
ether (5b). (a) The H-NMR yield based on mesitylene as the internal
standard. Reaction conditions: 0.5 mmol of 5a or 1 mmol of 5b, 2
mmol of Me3SiN3, 0.06 mmol of TMSCI, 50 mg of Na-Mont and 5 mL
of CH2Cl2. (b) Na-Mont was activated at 135 ꢂC in vacuum for 1 h prior
to the reaction, CH2Cl2 was distilled from CaH2 and used immediately
after the distillation.
Fig. 4 One-pot synthesis of 1,2,3-triazoles from alcohols. (a) The
isolated yield from column chromatography with using hexane/ethyl
acetate as eluents.(b) The reaction mixture was stirred for 4.5 h.
During the optimization of the reaction conditions, we
observed that when a mixture of 1a, Na-Mont, TMSCl, and
TMSN3 was stirred for 10 min at RT, 4a was afforded in 93%
yield together with the symmetrical ether of benzhydrol 5a in
2% yield (Table 1, entry 16). When the stirring period was pro-
longed, the yield of 4a increased along with the disappearance
of 5a, indicating that 5a seemed to be one of the intermediates
in the azidation.
To further elucidate the mechanism of the azidation, 5a
was subjected to the standard azidation conditions. Aer a 40
min reaction, 4a was formed in 49% yield together with 49%
of the intact 5a. In contrast, when the reaction was performed
using activated Na-Mont and anhydrous CH2Cl2, the yield of
4a dropped to 9%, suggesting the important role of trace
water in the azidation (Fig. 2). Based on these results together
with the other observations on the azidation, we proposed a
plausible mechanism for this azidation method as shown in
Fig. 3.
The reaction is most likely initiated by the hydrolysis of
TMSCl by water included in the Na-Mont or the solvent to
generate an equimolar amount of HCl, which is then trapped
by the Na-Mont. The HCl inside the Na-Mont promotes the
generation of a carbenium ion from an alcohol through
protonation and subsequent dehydration. The involvement of
carbenium ion-like species during the azidation reaction was
conrmed by the azidation of (R)-1-phenylethanol (98% ee)
which yielded a racemic mixture of the corresponding azides in
37% yield.16 The carbenium ion then reacts with TMSN3 to
generate the corresponding azide product as well as trime-
thylsilanol which is produced by the reaction with water. The
regeneration of a proton in the last step of the reaction explains
why the subsequent azidation can be repeated without any need
to supply more TMSCl.17
One of the most important applications of azides in organic
synthesis is the Cu(I)-catalysed Huisgen cycloadditions of azides
to alkynes to produce 1,2,3-triazoles.18 We also investigated the
possibility to perform a one-pot synthesis of 1,2,3-triazoles from
benzylic alcohols via the azidation and the successive click
reaction.19
Aer a screening of the reaction conditions, we found that
the combination of CuI catalyst with Et3N and propanoic acid
was suitable to perform the one-pot synthesis of 1,2,3-triazole
derivatives. A 0.5 equiv. of CuI was employed in the one-pot
synthesis since cycloaddition involving bulky azides, such as
4a, tends to take a longer time to reach completion.20 Benzylic
azides 4a, 4f, and 4i underwent the one-pot cycloaddition to give
the corresponding triazole derivatives in 99%, 76%, and 93%
yields, respectively (Fig. 4). However, the attempt to synthesize
the 1,2,3-triazole from a tertiary benzylic azide 4n failed, which
is probably due to steric effects of such a bulky azide.21
In conclusion, we developed a new and practical method to
convert natural montmorillonite into a solid acid catalyst using
a catalytic amount of TMSCl. The acidic montmorillonite
effectively catalysed the azidation of various benzylic alcohols at
ambient temperature. The reaction system allows the one-pot
synthesis of 1,2,3-triazole derivatives in combination with the
CuI catalysis.
Acknowledgements
We thank Prof. Shuichi Hiraoka of The University of Tokyo for
the HRMS analysis, and Prof. Tohru Yamada and Dr Tatsuyuki
Tsubo of Keio University for the chiral HPLC analysis.
Notes and references
1 Solid Supports and Catalysts in Organic Synthesis, ed. K.
Smith, Ellis Horwood and Prentice Hall, 1992, pp. 100–129.
2 H-Mont: K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani
and K. Kaneda, J. Org. Chem., 2007, 72, 6006–6015;
K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani
and K. Kaneda, Angew. Chem., Int. Ed., 2006, 45, 2605–2609.
Fig. 3 Plausible mechanism.
15738 | RSC Adv., 2015, 5, 15736–15739
This journal is © The Royal Society of Chemistry 2015