Categories: Synthesis of N-Heterocycles >
Synthesis of 1,2,3-triazoles and benzotriazoles
Name Reactions
Huisgen Azide-Alkyne 1,3-Dipolar Cycloaddition
Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC)
Ruthenium-Catalyzed Azide-Alkyne Cycloaddition (RuAAC)
Recent Literature
The synthesis of 1-monosubstituted aryl 1,2,3-triazoles was achieved in good
yields using calcium carbide as a source of acetylene. The copper-catalyzed
1,3-dipolar cycloaddition reactions were carried out without nitrogen protection
and in a MeCN-H2O mixture.
Y. Jiang, C. Kuang, Q. Yang, Synlett, 2009,
3163-3166.
A Pd-catalyzed synthesis of 1H-triazoles from alkenyl halides and
sodium azide represents a completely new reactivity pattern in the context of Pd
chemistry.
J. Barluenga, C. Valdés, G. Beltrán, M. Escribano, F. Aznar, Angew. Chem. Int. Ed., 2006, 45, 6893-6896.
J. Barluenga, C. Valdés, G. Beltrán, M. Escribano, F. Aznar, Angew. Chem. Int. Ed., 2006, 45, 6893-6896.
A tandem catalysis protocol based on decarboxylative coupling of alkynoic acids
and 1,3-dipolar cycloaddition of azides avoids usage of gaseous or highly
volatile terminal alkynes, reduces handling of potentially unstable and
explosive azides to a minimum, and furnishes various functionalized
1,2,3-triazoles in excellent yields and a very good purity without the need for
additional purification.
A. Kolarovič, M. Schnürch, M. D. Mihovilovic, J. Org. Chem., 2011,
76, 2613-2618.
4-Aryl-1H-1,2,3-triazoles were synthesized from anti-3-aryl-2,3-dibromopropanoic
acids and sodium azide by using inexpensive copper(I) iodide as the catalyst in
the presence of cesium carbonate as base and DMSO as solvent.
Y. Jiang, C. Kuang, Q. Yang, Synthesis, 2010,
4256-4260.
4-Aryl-1H-1,2,3-triazoles were synthesized from anti-3-aryl-2,3-dibromopropanoic
acids and sodium azide by a one-pot method using N,N-dimethylformamide as
solvent in the presence of Pd2(dba)3 and Xantphos.
W. Zhang, C. Kuang, Q. Yang, Synthesis, 2010,
283-287.
1-Substituted-1,2,3-triazoles were conveniently synthesized from the
corresponding aromatic and aliphatic azides in the presence of acetylene gas
using mild, copper(I)-catalyzed ‘click chemistry'.
L.-Y. Wu, Y.-X. Xie, Z.-S. Chen, Y.-N. Niu, Y.-M. Liang, Synlett, 2009,
1453-1456.
A true Click catalytic system is based on commercially available [CuBr(PPh3)3].
This system is active at room temperature, with catalyst loadings of 0.5 mol %
or less, in the absence of any additive, and it does not require any
purification step to isolate pure triazoles.
S. Lal, S. Díez-González, J. Org. Chem., 2011,
76, 2367-2373.
A well-defined copper(I) isonitrile complex is an efficient, heterogeneous
catalyst for azide-alkyne 1,3-dipolar cycloadditions and three-component
reactions of halides, sodium azide and alkynes to form 1,4-disubstituted
1,2,3-triazoles in high yields under mild conditions in water. The complex can
be recycled for at least five runs without significant loss of activity by
simple precipitation and filtration.
M. Liu, O. Reiser, Org. Lett., 2011,
13, 1102-1105.
Cycloadditions of copper(I) acetylides to azides and nitrile oxides provide
ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted
isoxazoles, respectively. The process is highly reliable and exhibits an
unusually wide scope with respect to both components. Computational studies
revealed a nonconcerted mechanism involving unprecedented metallacycle
intermediates.
F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless,
V. V. Fokin, J. Am. Chem. Soc., 2005,
127, 210-216.
1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl
azides and terminal alkynes in DMSO in the presence of a catalytic amount of
tetraalkylammonium hydroxide or t-BuOK for base-labile substrates. The
reaction is experimentally simple, does not require a transition-metal catalyst,
and is not sensitive to atmospheric oxygen and moisture.
S. W. Kwok, J. R. Fotsing, R. J. Fraser, V. O. Rodinov, V. V. Fokin, Org. Lett., 2010,
12, 4217-4219.
In the presence Cp*RuCl(PPh3)2 or Cp*RuCl(COD) as catalyst,
primary and secondary azides react with a broad range of terminal alkynes
containing a range of functionalities selectively producing 1,5-disubstituted
1,2,3-triazoles. Both complexes also promote the cycloaddition reactions of
organic azides with internal alkynes, providing access to fully-substituted
1,2,3-triazoles.
B. C. Boren, S. Narayan, L. K. Rasmussen, L. Zhang, H. Zhao, Z. Lin, G. Jia, V.
V. Fokin, J. Am. Chem. Soc., 2008,
130, 8923-8930.
A copper(I)-catalyzed three-component reaction of amines, propargyl halides and
azides forms 1-substituted-1H-1,2,3-triazol-4-ylmethyl)-dialkylamines in
water. Synthetic advantages are high atom economy, low environmental impact,
atmospheric oxygen, wide substrate scope, mild reaction condition and good
yields.
Z.-Y. Yan, Y.-B. Zhao, M.-J. Fan, W.-M. Liu, Y.-M. Liang, Tetrahedron, 2005,
61, 9331-9337.
A method for the regiospecific synthesis of
1,4,5-trisubstituted-1,2,3-triazole catalyzed by copper(I) iodide was developed.
This is the first example of a regiospecific synthesis of
5-iodo-1,4-disubstituted-1,2,3-triazole, which can be further elaborated to a
range of 1,4,5-trisubstituted-1,2,3-triazole derivatives.
Y.-M. Wu, J. Deng, Y. L. Li, Q.-Y. Chen, Synthesis, 2005,
1314-1318.
Inexpensive copper catalysts enabled modular one-pot multicomponent syntheses
of fully decorated triazoles through a sustainable “click” reaction/direct
arylation sequence.
L. Ackermann, H. K. Potukuchi, D. Landsberg, R. Vicente, Org. Lett.,
2008,
10, 3081-3084.
L. Ackermann, H. K. Potukuchi, D. Landsberg, R. Vicente, Org. Lett.,
2008,
10, 3081-3084.
Microwave irradiation significantly enhances the rate of formation of
1,4-disubstituted 1,2,3-triazoles from alkynes and in situ generated azides.
Azides are derived from an efficient one-pot azidation of anilines with the
reagent combination t-BuONO and TMSN3.
A. D. Moorhouse, J. E. Moses, Synlett, 2008,
2089-2092.
A reliable and operationally simple one-pot reaction for a one-carbon
homologation of various aldehydes followed by Cu-catalyzed azide-alkyne click
chemistry gives 1,4-disubstituted 1,2,3-triazoles in good yields without the
need for isolation of the alkyne intermediates.
D. Luvino, C. Amalric, M. Smietana, J.-J. Vasseur, Synlett, 2007,
3037-3041.
1,2,3-Triazoles were prepared in good to modest yields by cycloaddition of
alkyl azides onto enol ethers under solventless conditions. The reaction can
access ring-fused triazoles that are unavailable by azide-alkyne cycloadditions
and is easily scalable. The 1,2,3-triazole products bear functionality that may
be readily derivatized.
D. R. Rogue, J. L. Neill, J. W. Antoon, E. P. Stevens, Synthesis, 2005, 2497-2502.
Triazoles have been synthesized via a three-component coupling reaction of
unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under
Pd(0)-Cu(I) bimetallic catalysis. The deallylation of the resulting
allyltriazoles is described.
S. Kamijo, T. Jin, Z. Huo, Y. Yamamoto, J. Am. Chem. Soc., 2003, 125, 7786-7787.
Reaction of 4-bromo-NH-1,2,3-triazoles with alkyl halides in the presence
of K2CO3 in DMF produced the corresponding 2-substituted
4-bromo-1,2,3-triazoles in a regioselective process. Subsequent Suzuki
cross-coupling reaction provided an efficient synthesis of 2,4,5-trisubstituted
triazoles, whereas hydrogenation furnished an efficient synthesis of
2,4-disubstituted triazoles.
X.-j. Wang, K. Sidhu, L. Zhang, S. Campbell, N. Haddad, D. C. Reeves, D.
Krishnamurthy, C. H. Senanayake, Org. Lett., 2009,
11, 5460-5493.
A palladium-catalyzed and ultrasonic promoted Sonogashira coupling/1,3-dipolar
cycloaddition of acid chlorides, terminal acetylenes, and sodium azide in one
pot enables an efficient synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles in
excellent yields.
J. Li, D. Wang, Y. Zhang, J. Li, B. Chen, Org. Lett., 2009,
11, 3024-3027.
TBAF-catalyzed [3 + 2] cycloadditions of 2-aryl-1-cyano- or
2-aryl-1-carbethoxy-1-nitroethenes with TMSN3 under solvent free
conditions allow the preparation of 4-aryl-5-cyano- or 4-aryl-5-carbethoxy-1H-1,2,3-triazoles under mild reaction conditions with good to excellent yields.
D. Amantini, F. Fringuelli, O. Piermatti, F. Pizzo, E. Zunino, L. Vaccaro, J. Org. Chem., 2005, 70, 6526-6529.
D. Amantini, F. Fringuelli, O. Piermatti, F. Pizzo, E. Zunino, L. Vaccaro, J. Org. Chem., 2005, 70, 6526-6529.
Triazole-based monophosphine ligands have been prepared via efficient
cycloadditions. Palladium complexes derived from these ligands are highly
active catalysts for Suzuki-Miyaura coupling and amination reactions of aryl
chlorides.
D. Liu, W. Gao, Q. Dai, X. Zhang, Org. Lett.,
2005, 7, 4907-4910.
A highly efficient method for the synthesis of multisubstituted 1,2,3-triazoles
via a direct Pd-catalyzed C-5 arylation has been developed.
S. Chuprakov, N. Chernyak, A. S. Dudnik, V. Gevorgyan, Org. Lett., 2007,
9, 2333-2336.
The use of nontoxic polyethylene glycol (PEG) as solvent and MesCO2H
as cocatalyst enabled user-friendly palladium(0)-catalyzed C-H bond
functionalizations under air in the absence of phosphine ligands. Direct
arylations of 1,2,3-triazoles gave substituted triazoles in good yields.
Recycling of the catalytic system led to a slight decrease of activity.
L. Ackermann, R. Vicente, Org. Lett., 2009,
11, 4922-4925.
Conditions for the palladium-catalyzed direct arylation of a wide range of
heterocycles with aryl bromides employ a stoichiometric ratio of both coupling
partners, as well as a substoichiometric quantity of pivalic acid, which results
in significantly faster reactions. An evaluation of the influence of the nature
of the aryl halide has also been carried out.
B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem., 2009,
74, 1826-1834.
A [3 + 2] cycloaddition of azides to benzynes affords a rapid and easy entry to
a variety of substituted, functionalized benzotriazoles under mild conditions.
F. Shi, J. P. Waldo, Y. Chen, R. C. Larock, Org. Lett., 2008,
10, 2409-2412.
A 1,7-palladium migration-cyclization-dealkylation sequence for the
regioselective synthesis of benzotriazoles proceed in excellent yields with high
regioselectivities. The mechanism of the reaction has also been investigated.
J. Zhou, J. He, B. Wang, W. Yang, H. Ren, J. Am. Chem. Soc., 2011,
133, 6868-6870.
C-H activation of aryl triazene compounds followed by intramolecular amination
in the presence of a catalytic amount of Pd(OAc)2 provides 1-aryl-1H-benzotriazoles
at moderate temperature.
R. K. Kumar, M. A. Ali, T. Punniyamurthy, Org. Lett., 2011,
13, 2102-2105.
