Categories: Synthesis of N-Heterocycles >
Synthesis of pyrazoles and indazoles
Recent Literature

1,3-Diketones, which were synthesized in situ from ketones and acid
chlorides, were converted into pyrazoles by the addition of hydrazine. This
method allows a fast and general synthesis of previously inaccessible
pyrazoles and synthetically demanding pyrazole-containing fused rings.
S. T. Heller, S. R. Natarajan, Org. Lett.,
2006, 8, 2675-2678.

A highly regioselective synthesis of 1-aryl-3,4,5-substituted pyrazoles based on
the condensation of 1,3-diketones with arylhydrazines proceeds at room
temperature in N,N-dimethylacetamide and furnishes pyrazoles in good
yields.
F. Gosselin, P. D. O'Shea, R. A. Webster, R. A. Reamer, R. D. Tillyer, E. J. J.
Grabowski, Synlett, 2006,
3267-3270.

Pyrazole or isoxazole derivatives are prepared by a palladium-catalyzed four-component coupling of a terminal alkyne, hydrazine (hydroxylamine),
carbon monoxide under ambient pressure, and an aryl iodide.
M. S. M. Ahmed, K. Kobayashi, A. Mori, Org. Lett.,
2005, 7, 4487-4489.

A simple one-pot method allows the synthesis of diversely functionalized N-arylpyrazoles from aryl nucleophiles, di-tert-butylazodicarboxlate, and
1,3-dicarbonyl or equivalent compounds.
B. S. Gerstenberger, M. R. Rauckhorst, J. T. Starr, Org. Lett., 2009,
11, 2097-2100.

M. S. M. Ahmed, K. Kobayashi, A. Mori, Org. Lett.,
2005, 7, 4487-4489.

A regioselective synthesis of tri- or tetrasubstituted
pyrazoles by the reaction of hydrazones with nitroolefins mediated
with strong bases such as t-BuOK exhibits a reversed, exclusive
1,3,4-regioselectivity. Subsequent quenching with strong acids such as TFA is
essential to achieve good yields. A stepwise cycloaddition reaction
mechanism is proposed.
X. Deng, N. S. Mani, Org. Lett., 2008,
10, 1307-1310.

Two general protocols for the reaction of electron-deficient N-arylhydrazones
with nitroolefins allow a regioselective synthesis of 1,3,5-tri- and
1,3,4,5-tetrasubstituted pyrazoles. Studies on the stereochemistry of the key
pyrazolidine intermediate suggest a stepwise cycloaddition mechanism.
X. Deng, N. S. Mani, J. Org. Chem., 2008,
73, 2412-2415.

A regioselective one-pot synthesis of substituted pyrazoles from N-monosubstituted
hydrazones and nitroolefins gives products in good yields. A key
nitropyrazolidine intermediate is characterized and a plausible mechanism is
proposed.
X. Deng, N. S. Mani, Org. Lett.,
2006, 8, 3505-3508.

A general, highly flexible Cu-catalyzed domino C-N coupling/hydroamination
reaction constitutes a straightforward alternative to existing methodology
for the preparation of pyrroles and pyrazoles.
R. Martin, M. R. Rivero, S. L. Buchwald, Angew. Chem. Int. Ed., 2006, 45, 7079-7082.

Various 1-acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles have been prepared in
good yields from the corresponding 2-alkyn-1-ones. The resulting
dihydropyrazoles undergo dehydration and iodination in the presence of ICl and
Li2CO3 at room temperature to provide 1-acyl-4-iodo-1H-pyrazoles.
J. P. Waldo, S. Mehta, R. C. Larock, J. Org. Chem., 2008,
73, 6666-6670.

A series of 4-substituted 1H-pyrazole-5-carboxylates was prepared from
the cyclocondensation reaction of unsymmetrical enaminodiketones with tert-butylhydrazine
hydrochloride or carboxymethylhydrazine. The compounds were obtained
regiospecifically and in very good yields.
F. A. Rosa, P. Machado, P. S. Vargas, H. G. Bonacorso, N. Zanatta, M. A. P.
Martins, Synlett, 2008,
1673-1678.

An easy and efficient copper-catalyzed reaction for the synthesis of
polysubstituted pyrazoles from phenylhydrazones and dialkyl
ethylenedicarboxylates tolerates a range of functionalities, and the
corresponding adducts can be obtained in moderate to good yields.
C. Ma, Y. Li, P. Wen, R. Yan, Z. Ren, G. Huang, Synlett, 2011,
1321-1323.

The reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or
ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the
synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction
with ethyl propiolate or dimethyl acetylenedicarboxylate.
Y. Hari, S. Tsuchida, R. Sone, T. Aoyama, Synthesis, 2007,
3371-3375.

In the presence of activated carbon, Hantzsch 1,4-dihydropyridines and
1,3,5-trisubstituted pyrazolines were aromatized with molecular oxygen to the
corresponding pyridines and pyrazoles in excellent yields.
N. Nakamichi, Y. Kawashita, M. Hayashi, Synthesis, 2004,
1015-1020.

Various N-aryl-1H-indazoles and benzimidazoles were synthesized
from common arylamino oximes in good to excellent yields depending upon the base
used in the reaction. Triethylamine promoted the formation of benzimidazoles,
whereas 2-aminopyridine promoted the formation of N-arylindazoles.
B. C. Wray, J. P. Stambuli, Org. Lett., 2010,
12, 4576-4579.

A rapid and efficient synthesis of 2H-indazoles, which involves a [3 + 2]
dipolar cycloaddition of arynes and sydnones, proceeds under mild reaction
conditions in good to excellent yields.
C. Wu, Y. Fang, R. C. Larock, F. Shi, Org. Lett., 2010,
12, 2171-2173.

A general two-step synthesis of substituted 3-aminoindazoles from
2-bromobenzonitriles involves a palladium-catalyzed arylation of benzophenone
hydrazone followed by an acidic deprotection/cyclization sequence. This
procedure offers a general and efficient alternative to the typical SNAr
reaction of hydrazine with o-fluorobenzonitriles.
V. Lefebvre, T. Cailly, F. Fabis, S. Rault, J. Org. Chem., 2010,
75, 2730-2732.

Readily available, stable, and inexpensive N-tosylhydrazones react with
arynes under mild reaction conditions to afford 3-substituted indazoles in good
yields. The reaction involves a 1,3-dipolar cycloaddition of in situ
generated diazo compounds and arynes.
P. Li, J. Zhao, C. Wu, R. C. Larock, F. Shi, Org. Lett., 2011,
13, 3340-3343.

The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl
triflates in the presence of CsF or TBAF at room temperature provides a very
direct, efficient approach to a wide range of potentially biologically and
pharmaceutically interesting substituted indazoles in good to excellent yields
under mild reaction conditions.
Z. Liu, F. Shi, P. D. G. Martinze, C. Raminelli, R. C. Larock, J. Org. Chem., 2008,
73, 219-226.
