Product Class 13: 1,2,3-Triazoles

N-Unsubstituted 1,2,3-triazoles can be regarded either as 1H- oras2H-derivatives since
these two tautomeric forms are in equilibrium, both in solution and in the gas phase
(Scheme 2). In this article, for simplification, this type of compound will be represented
as 1H-triazoles, independently of the predominant tautomer.
Scheme 2 Tautomerism in 1,2,3-Triazoles
N
N 2
1N
H
N
2
NH
N
1
1H-1,2,3-triazole 2H-1,2,3-triazole
N
N 2
N
1
H
FOR PERSONAL USE ONLY
416 Science of Synthesis 13.13 1,2,3-Triazoles
N
2
NH
N
1
1H-benzotriazole 2H-benzotriazole
The two tautomeric forms of 1,2,3-triazole and benzotriazole are in equilibrium, both in
solution and in the gas phase (Scheme 2). However there is an extraordinary difference in
stability between 1,2,3-triazole and benzotriazole tautomers. In the gas phase, the 2H-tautomer
of 1,2,3-triazole represents more than 99.9% of the equilibrium mixture, whereas
in benzotriazole the 1H-tautomer is the predominant one (more than 99.99% at equilibrium).
[10] In solution, the much higher dipole moment of 1H-tautomers favor these structures
and, as a consequence, mixtures of 1H- and 2H-1,2,3-triazole are observed in solution
whereas the higher stability of 1H-benzotriazole is reinforced. [10] In the solid state,
1,2,3-triazole exists as a 1:1 mixture of 1H- and 2H-tautomers, while 4-phenyl-1,2,3-triazole
and 4-nitro-1,2,3-triazole are, respectively, in the 2H- and 1H- tautomeric forms. [11]
The experimental dipole moment in benzene for the tautomeric mixture of 1H- and 2H-
1,2,3-triazole is 1.85 D at 258C and 2.08 D at 458C. The experimental dipole moments are
as follows: 1H-1,2,3-triazole 4.38 D, 2H-1,2,3-triazole 0.22 D, 1H-benzotriazole 4.15 D, and
2-methyl-2H-benzotriazole 0.49 D. [7]
1H-1,2,3-Triazole is both a weak base (pK a 1.17) and a weak acid (pK a 9.4) of comparable
strength to phenol. 1H-1,2,3-Triazole-4,5-dicarbonitrile (pK a 2.53), 4,5-dibromo-1H-
1,2,3-triazole (pK a 5.37), and 4-nitro-1H-1,2,3-triazole (pK a 4.80) are much more acidic compounds.
1-Methyl-1H-1,2,3-triazole (pK a 1.25) shows a basicity comparable to 1H-1,2,3-triazole,
but 2-methyl-2H-1,2,3-triazole is a much weaker base. [12–14] The basicity of N-unsubstituted
and N-methyl-1,2,3-triazoles in the gas phase, in solution, and in the solid state
has been determined. [11] The fused benzene ring in benzotriazole (pK a 8.2) is base-weakening
and acid-strengthening. Substitution of hydrogen atoms by chlorine in the benzene
ring results in increased acidity: 5-chlorobenzotriazole, pK a 7.7; 4,5,6,7-tetrachlorobenzotriazole,
pK a 5.5. [15,16]
The application of semi-empirical and ab initio methods in theoretical calculations
for 1,2,3-triazoles and benzotriazoles and the description of a number of instrumental
techniques used in the characterization of these systems have been reviewed. [7]
1,2,3-Triazoles with a strong electron-withdrawing group at N1 (e.g., cyano, nitro, or
arylsulfonyl groups) undergo ready and reversible ring opening to Æ-diazoimine tautomers
(Scheme 3). This ring–chain tautomerism, also observed in some benzotriazole derivatives,
is markedly temperature dependent. [17–20]
A. C. TomØ, Section 13.13, Science of Synthesis, 2004 Georg Thieme Verlag KG