On the relationship between thermodynamic pK,'s of azoles and the oxidation potentials

of their pentacyanoferrate(I1)complexes
VICENTALOPEZAND JAVIERCATALAN
Departamento de Quimica, Facultad de Ciencias, Universidad Autdnoma de Madrid, Cantoblanco, 28049 Madrid, Spain
AND

ROSAM~ CLARAMUNT, CONCEPCION LOPEZ,EDUARDO CAYON,'AND JOSEELGUERO

Departamento de Quimica Organica and Institute de Quimica Me'dica, UNED and CSIC, Ciudad Universitaria,
28040 Madrid, Spain
Received August 20, 1989

VICENTA LOPEZ,JAVIER CATALAN, ROSAMA CLARAMUNT, CONCEPCION LOPEZ,EDUARDO CAYON, and JOSEELGUERO.
Can. J. Chem. 68, 958 (1990).
The comparison between thermodynamic pKa values and oxidation potentials of the pentacyanoferrate(I1) complexes of a
series of azoles shows the existence of two parallel lines: one for pyrazoles and another one for benzazoles. Using the equation
corresponding to the second one, the pKa value of 1-methylbenzotriazole(2.49) can be estimated from the value of its
complex.
Key words: azole basicity, oxidation potentials, pyrazoles, benzotriazoles.

VICENTA LOPEZ,J A V ~ E CATALAN,

R ROSAM~ CLARAMUNT, CONCEPCION LOPEZ,EDUARDO CAYON et JOSEELGUERO. Can.
J. Chem. 68, 958 (1990).
La comparaison entre les pKa thermodynamiques d'une serie d'azoles et les potentiels d'oxydation de leurs complexes avec
l'anion pentacyanoferrate(I1)montre l'existence de deux relations lineaires, une pour les pyrazoles et l'autre pour les benzazoles.
La seconde permet d'estimer le pKa du methyl-1 benzotriazole (2,49) a partir de la valeur de de son complexe.
Mots cle's : basicit6 des azoles, potentiels d'oxydation, pyrazoles, benzotriazoles.
[Traduit par la revue]

Introduction TABLE1. Half-wave potentials (mV) of the com-

plexes and pK, values (proton gain) of the azole ligand
Our interest in the acid-base properties of azoles (1)
prompted us to study Brisset and Ilimby's method (2) of indirect
determination of the basicity of pyrazoles and indazoles. This No. Ligand Ea1/2 pKt
method has the advantage that it can be used to determine the Pyrazole 192 R 2.48
pKa of very weak bases. Since ElI2is constant for a wide range 3(5)-Methyl 152 R 3.27
of pH values, it is possible to determine the pKa value without 3,5-Dimethyl 136 R 4.06
reaching the pH zone corresponding to the pKa. Following 1,3,5-Trimethyl 160.5QR 3.74
previous studies on pyridines, these authors determined the 4-Phenyl 203.5 QR 1.64
oxidation potentials ElI2(in mV) of the pentacyanoferrate(I1) 3,5-Diphenyl 198.5NR 1.75
complexes of five pyrazoles (pyrazole itself, 3(5)-methyl- 4-Bromo 240 R 0.63
pyrazole, 33-dimethylpyrazole, 6chloropyrazole, and l-methyl- 1-Nitro 180.5 NR -4.15
pyrazole) and of indazole, and postulated the existence of a 3(5)-Nitro 332.5NR -4.66
4-Nitro 301 R -2.0
linear relationship between ElI2 and the corresponding pKa
3,5-Dimethyl-4-nitro 263 NR -0.45
(proton gain) of tfie free ligands:
1,2,4-Triazole 233.5QR 2.45
Benzimidazole 140 QR 5.56
With this equation and the experimental ElI2values of other 2-Methyl 127.5QR 6.19
pyrazoles and indazoles they predicted the pKa of the following 1-Ethyl-2-methyl 128QR 6.30
compounds: 1-acetylpyrazole (2.99, reported in ref. I), 4-nitro- Indazole 265.5QR 1.04
indazole (0.25, reported in ref. I), 5-nitroindazole (-0.04), 5-Nitro 317.5NR -0.96
6-nitroindazole (0.49), 7-nitroindazole (-1.00, reported in 6-Nitro 323.5 QR -0.97
ref. I), and 5,6-dinitroindazole (-0.90, reported in ref. 1). The Benzotriazole 243.5QR 1.6
values for 5- and 6-nitroindazoles were not reported in ref. 1
1-Methyl 226 R C
since we had previously determined (3) their thermodynamic
pKals (-0.96 and -0.97, respectively). "R:reversible, QR: quasi-reversible,NR: not reversible.
Due to the discrepancies involving the last two compounds, bAll values from ref. 1 save that of compound 15 taken
we decided to test the method of Brisset and llimby (2) using a from ref. 5.
larger and better-balanced set of azoles. 'Unknown.

Experimental dissolving solid Na3Fe(CN)5NH3(2) and the corresponding azole or

All the are commercially available or were prepared by
conventional methods (4). The complexes were prepared in situ by
'on leave from the Universidad Aut6noma de Barcelona, Spain.
Printed in Canada I Imprim6 au Canada
benzazole in a ratio close to 1:10 in a 0.5 M electrolytic soluti~nof
NaC104. The pH was varied by small additions of strong acid (HC104)
or base (NaOH). The electrochemical method used was identical to
that described by Brisset and Ilimby (2).
 LOPEZ ET AL

FIG. 1. Representation of the half-wave potentials vs. the pK,'s. Pyrazoles (a);benzazoles (0);
1,2,4-triazole (A).

Results and discussion
Table 1 contains the EIl2values determined here together
with the thermodynamic pKa values; the corresponding bi-
dimensional plot is that represented in Fig. 1.
The following conclusions can be drawn:
(i) Two parallel lines are observed, pyrazoles having a
special behaviour as in other studies dealing with their basicity
or acidity (6, 7).
(ii) All benzazoles have been included in the linear regres-
sion, which yields eq. [2].
[2] Ell2 = 292.7 - 26.8pKa n = 7 , 2 = 0.998
I
(iii) Nitropyrazoles 8 and 9 have been excluded from the
regression leading to eq. [3].
(iv) 1,2,4-Triazole 12 is near the line for the benzazoles.
From eq. [2']
points belonging to both lines, pyrazoles 1 , 2 , 3 , and 4-chloro-
pyrazole, and benzazoles, indazole 16. With our values for
compounds 1, 2, 3, and 16, the following equation is found:
Ell2 = 306.6 - 44.3 pKa, n = 4 , r 2 = 0.98, which is close to
e q ill.
It is not possible to use the ElI2values of ref. 2 and our
equations [2] and [3] to calculate the pKa of the compounds
studied by Brisset and Ilimby, since for common derivatives the
El12values differ. However, with their EIl2value for 4-chloro-
pyrazole (225), eq. [3] yields pKa = 0.88, which is much closer
to the thermodynamic value (0.59 (1)) than the value calculated
with eq. [ l ] (1.86 (2)).
Acknowledgements
We thank the ComitC Conjunto Hispano-Norteamericano
para la Cooperaci6n Cientifica y Tecnol6gica for financial
support (CCB 86/04/009). One of us (C.L.) is indebted to the
Consejeria de Educaci6n y Juventud de la Comunidad de
Madrid of Spain for a grant.

and from the Ell, value of 1-methylbenzotriazole 20, its pKa can 1. J. CATALAN, J. L. M. ABBOUD, and J. ELGUERO. Adv. Hetero-
cycl. Chem. 41, 187 (1987).
be estimated (2.49). The pyrazoles that behave abnormally, 8 2. J. L. BRISSET and V. ILIMBI.Can. J. Chem. 58, 1250 (1980), and
I
and 9, both have a nitro group near the basic center: references therein.
3. J. ELGUERO, A. FRUCHIER, and R. JACQUIER. Bull. Soc. Chim.
Fr. 2619 (1967).
4. A. R. KATRITZKY and C. W. REES.Comprehensive heterocyclic
chemistry. Pergarnon Press, Oxford. 1984.
5. M. KRISHNAMURTHY, P. PHANIRAJ, and S. K. DOGRA. J. Chem.
Soc. Perkin Trans. 2, 1917 (1986).
8 9 6. J. CATALAN and J . ELGUERO. J. Chem. Soc. PerkinTrans. 2,1869
This situation could interfere with the complex formation. (1983).
7. J. CATALAN, 0 . Mo, J. L. G. DE PAZ,P. PEREZ,M. YAREZ,and
I
The fact that the value of the slope in eq. [ l ] is twice those of J. ELGUERO. J. Org. Chem. 49,4379 (1984).
eqs. [2] and [3] results from the fact that it was calculated using