LETTER
A Complementary Approach to 3,5-Substituted Pyrazoles
2091
O
O
TfOH, DCE, reflux
Br
N
Br
N
HN
N
H
8
O
7
N
Ts
O
Br
N
H
Ph
6
N
Br
NH
Ph
TfOH, DCE, reflux
9
62%
Scheme 4 Controlled experiments for the mechanism
(6) For recent methods, see: (a) Zora, M.; Kivrak, A.; Yazici, C.
J. Org. Chem. 2011, 76, 6726. (b) Babinski, D. J.; Aguilar,
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Sanchez-Rosello, M.; Barrio, P.; Simon-Fuentes, A. Chem.
Rev. 2011, 111, 6984; and references cited therein.
(7) (a) For a recent review, see: Fulton, J. R.; Aggarwal, V. K.;
de Vicente, J. Eur. J. Org. Chem. 2005, 1479. (b) For a
selective example: Aggarwal, V. K.; de Vicente, J.; Bonnert,
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(8) Bamford, W. R.; Stevens, T. S. J. Chem. Soc. 1952, 4735.
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Synthesis 2011, 2767.
be a competitive side process while path b is a main pro-
cess.
In order to rule out the possible diazo intermediate existed
in the reaction, we performed compound 6 under standard
conditions. In the absence of phenylacetylene, the intra-
molecular carbocation cycloaddition was almost prohibit-
ed probably due to the serious steric hindrance (Scheme 4,
compound 8), but we could not detect compound 7 via the
intramolecular 1,3-dipolar cycloaddition of the diazo in-
termediate (Scheme 1, path a);19 on the other hand, in the
presence of phenylacetylene, we could isolate the inter-
molecular cycloaddition product 9 in 62% yield. All these
results strongly suggested that our process did not involve
the diazo intermediate.
In summary, a TfOH-induced addition involving a carbo-
cation addition of tosylhydrazones to the terminal alkynes
has been explored, which leads to 3,5-substituted pyr-
azoles in moderate to high yields.20 This acid-induced ad-
dition might be an intrinsically safer operation compared
to the typical 1,3-dipolar cycloaddition involving diazo
compounds.
Acknowledgment
We thank National Natural Foundation of China (20872019) and
Fudan University for the financial support. We are grateful to Dr.
Hanqing Dong for his helpful discussion.
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Supporting Information for this article is available online at
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References and Notes
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(14) The NMR spectra of the synthetic sample 3a are in a good
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Synlett 2012, 23, 2087–2092