Polynuclear branched tetrazole systems. 3. Acidity of α,ω- ditetrazol-5-ylalkanes

Article abstract of DOI:10.1007/s10593-006-0113-3

α,ω-Ditetrazol-5-ylalkanes with 1 to 5 methylene groups in the alkyl fragment display the properties of dibasic heterocyclic NH acids with pK_a values lying in the range 3.4-6.1. The pK_a values of these compounds are in a linear dependence on the values of the dielectric permeability of the medium, on the chemical shifts of the signals of the endocyclic carbon atom, and of the carbon atom of the α-methylene group in the ¹³C NMR spectra. 2006 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0113-3

Chemistry of Heterocyclic Compounds, Vol. 42, No. 4, 2006
POLYNUCLEAR BRANCHED TETRAZOLE SYSTEMS.
3*. ACIDITY OF α,ω-DITETRAZOL-5-YLALKANES
V. Yu. Zubarev, R. E. Trifonov, V. V. Poborchii, and V. A. Ostrovskii
α,ω-Ditetrazol-5-ylalkanes with 1 to 5 methylene groups in the alkyl fragment display the properties of
dibasic heterocyclic NH acids with pKa values lying in the range 3.4-6.1. The pKa values of these
compounds are in a linear dependence on the values of the dielectric permeability of the medium, on the
chemical shifts of the signals of the endocyclic carbon atom, and of the carbon atom of the α-methylene
group in the 13C NMR spectra.
Keywords: α,ω-ditetrazol-5-ylalkanes, 1,3-dipolar cycloaddition, acidity, potentiometry, NMR
spectroscopy.
It is known that multibasic carboxylic acids are efficient ligands for binding metal ions into stable
complexes [2]. The search for compounds possessing similar or greater complex-forming activity is an urgent
problem. The polynuclear heterocyclic systems are extremely promising in this aspect. They are analogs of
multibasic carboxylic acids in which the carboxyl groups are replaced by tetrazol-5-yl fragments. The
NH-tetrazole ring possesses acidity close to a carboxyl group and is able to form stable complexes with metal
ions. Comparison of the complex-forming ability of standard complexones containing carboxyl fragments in
their structure, and their tetrazol-5-yl analogs in relation to ions of copper, cobalt, and nickel showed a
preference for these heterocyclic derivatives [3]. The complex-forming activity of ligands may also be assessed
from their acid-base properties [2].
Previously we synthesized polynuclear 2-(tetrazol-5-yl)ethyl compounds and investigated their acidic
properties [1, 4]. Nonetheless the significant differences in the structure and in the solubility of these compounds
does not permit a structure–property or property–property dependence to be reached correctly.
In the present work, using 1,3-dipolar cycloaddition of alkylammonium azides to dinitriles of
dicarboxylic acids, ditetrazol-5-ylalkanes 1-5 with the number of methylene groups in the aliphatic fragment
from 1 to 5 have been synthesized. Their acidic properties have been investigated. The 5,5'-ditetrazole 6 has been
considered as a model compound.
H
N
N
N
N
N
N
(CH2)n
N
H
N
1–6
1 n = 1, 2 n = 2, 3 n = 3, 4 n = 4, 5 n = 5, 6 n = 0
_______
* For Part 2 see [1].
__________________________________________________________________________________________
Saint Petersburg State Technological Institute (Technical University), Saint Petersburg 198013, Russia;
e-mail: va_ostrovskii@mail.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535-541,
April. 2006. Original article submitted December 20, 2005.
0009-3122/06/4204-0469©2006 Springer Science+Business Media, Inc.
469

The values of pKa1 and pKa2, characterizing the acidity of the dibasic aliphatic carboxylic acids, have
been known for a fairly long time [5]. The acid–base properties of only 5,5'-ditetrazole 6 were investigated
quantitatively among the dibasic tetrazoles [6].
The acid dissociation of α,ω-ditetrazol-5-ylalkanes 1-5 occurs stepwise with the formation of the
corresponding mono and dianions.
H
N
N
N
N
N
N
N
N
N
N
N
N
(CH2)n
(CH2)n
–
–
N
H
N
N
N
Ka2
Ka1
+
+
– H
– H
N
–
N
N
N
(CH2)n
N
N
N
N
H
As follows from the data of Table 1, the pKa values of compounds 1-5, determined by potentiometric
titration, are in the range 3.4-6.1 (for water). The acidity of these compounds therefore proved to be close to the
acidity of the corresponding dibasic aliphatic carboxylic acids [5]. However clear correlation dependencies
linking the values of pKa1 and pKa2 of tetrazoles 1-6 and the corresponding dicarboxylic acids failed to be
exposed.
On increasing the number of bridge methylene groups (n) a tendency towards an increase in the pKa
value is seen (Fig. 1). However it may be observed from Figure 1 that at n > 5 these changes of pKa value
become insignificant. We note that at n = 5 the value of ∆pKa, calculated as the difference between the acidity
constants for the first and second stages (∆pKa = pKa2 – pKa1), approaches the value of log 4, a statistical effect
determined by the difference in the number of acidity centers at the first and second stages, although not equal to
it. This fact may indicate the weak mutual electronic influence of the tetrazole rings [7].
To estimate the influence of solvation effects on the acid dissociation of ditetrazoles 1-5 in water–
organic solvent systems we have established the dependency of pKa1 and pKa2 values on the dielectric
permeability of the medium in the system methanol–0.1 N aqueous NaNO3 solution with a methanol content
from 0 to 50 wt.% (Table 2). Values of the correlation parameters of the linear dependencies of pKa1 and pKa2 on
1/ε are shown in Table 3.
According to Tables 2 and 3 the values of the solvation coefficients (a, b) for all the compounds 1-5
investigated are approximately equal. This circumstance permits the suggestion of a related character for the
solvation of each compound in the given binary solvent [8].
TABLE 1. Thermodynamic Acid Dissociation Constants of α,ω-Ditetrazol-
5-ylalkanes 1-5 and 5,5'-Ditetrazole 6 at the First and Second Stages
Compound
n
pKa1
pKa2
1
2
3
4
5
6
1
2
3
4
5
0
3.42±0.01
4.42±0.03
4.95±0.01
5.17±0.02
5.23±0.01
1.41[6]
5.30±0.02
5.74±0.03
5.94±0.02
6.09±0.03
6.10±0.03
4.25[6]
470

471

n
Fig. 1. Dependency of the acidity constant of ditetrazoles 1-6 on the number
(n) of methylene groups.
TABLE 3. Statistical Parameters of the Correlation Dependency of the Acid
Dissociation Constants of α,ω-Ditetrazol-5-ylalkanes on the Reciprocal
Dielectric Permeability of the Medium
pKa1 = a (1/ε) + b
pKa2 = a (1/ε) + b
Com-
pound
a
b
r
s
a
b
r
s
1
2
3
4
5
35±6
39±6
34±2
30±5
40±5
2.84±0.09
3.78±0.09
4.54±0.04
4.67±0.07
4.59±0.07
0.95
0.96
0.98
0.95
0.97
0.02
0.02
0.01
0.02
0.02
55±6
44±6
45±5
43±8
50±6
4.46±0.09
5.07±0.09
5.28±0.08
5.43±0.13
5.33±0.10
0.98
0.96
0.97
0.93
0.97
0.03
0.03
0.02
0.03
0.03
It was shown previously by the authors of [9] that for 5-substituted tetrazoles a linear dependency exists
between the chemical shift of the signals of the endocyclic carbon atom of the tetrazole ring in the 13C NMR
spectra and pKa. We have also found analogous correlation dependencies (1), (2) for the sizes of pKa1 and pKa2 of
compounds 1-5.
pKa1 = (0.528 ± 0.048) × δ(C5 ) – (77.302 ± 7.481), r = 0.99, s = 0.14, n = 5 (1)
T
pKa2 = (0.233 ± 0.023) × δ(C5 ) – (30.274 ± 3.633), r = 0.98, s = 0.07, n = 5 (2)
T
Different correlation dependencies (3) and (4) were also made apparent for tetrazoles 1-5, linking the
acid dissociation constants at the first and second stages with the values of the chemical shift of the signals of the
carbon atom of the α-methylene groups.
472

pKa1 = (0.515 ± 0.018) × δ(Cα-СН2) – (6.410 ± 0.378), r = 0.99, s = 0.05, n = 5 (3)
pKa2 = (0.227 ± 0.015) × δ(Cα-СН2) + (0.975 ± 0.318), r = 0.99, s = 0.04, n = 5 (4)
The established correlation ratios may be used, with a high degree of confidence, for predicting on the
basis of NMR spectroscopic data the acid–base properties of compounds belonging to the α,ω-ditetrazol-5-
ylalkane series.
The values of pKa1 and pKa2 obtained in the present study enable selection of such values of the pH of
the medium at which only undissociated molecules, monoanions, or dianions, predominantly exist. This has a
decisive value in processes of complex-formation (tetrazolate anions form more stable chelate complexes with
metal ions), and may also be valuable when assessing the reactivity of compounds of this type.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on a Bruker DPX 300 (300 and 75 MHz respectively) in
DMSO, internal standard was the solvent signal. The IR spectra were recorded on a Shimadzu FTIR 8400
instrument in KBr disks. Elemental analysis was carried out on a Hewlett-Packard 185B C,H,N analyzer.
Melting points were determined on a PTP type of instrument with a heating rate of 1°C/min in the melting range.
Potentiometric titration was carried out on a pH 121 potentiometer (electrodes: glass EVL-1M3, silver chloride
ESL-63-07T4.1). All potentiometric measurements were made at 25°C. Values of pKa were calculated according
to [8].
α,ω-Ditetrazol-5-ylalkanes (general procedure using ditetrazol-5-ylmethane 1 as an example). A
mixture of malononitrile (12.0 g, 182 mmol), sodium azide (26.0 g, 400 mmol), and dimethylamine
hydrochloride (32.6 g, 400 mmol) in DMF (70 ml) was maintained at 107-112°C for 12 h. The reaction mixture
was then filtered, and the solvent evaporated in vacuum. The residue was dissolved in distilled water (50 ml) and
acidified with dilute hydrochloric acid to pH 1. The precipitated solid was filtered off, washed with water, and
dried. Compound 1 (23.5 g, 85%) of mp 210°C was obtained. After purification by reprecipitation with active
carbon and recrystallization from 2-propanol colorless crystals of mp 214°C were obtained. IR spectrum, ν, cm-1:
2800-3200 (NH), 1567, 1452, 1432, 1405, 1273, 1242, 1197, 1105, 1076. 1H NMR spectrum, δ, ppm: 4.75 (2H,
s, CH2CN4H); 15.55 (2H, br. s, CN4H). 13C NMR spectrum, δ, ppm: 152.5 (tetrazole); 19.1 (CH2CN4H). Found,
%: C 23.80; H 3.32; N 73.14. C3H4N8. Calculated, %: C 23.69; H 2.65; N 73.66.
1,2-Di(tetrazol-5-yl)ethane (2). Yield 16.4 g (82%); mp 244°C (2-propanol). IR spectrum, ν, cm-1:
2800-3200 (NH), 1586, 1455, 1414, 1261, 1118, 1114, 1102, 1062, 1002. 1H NMR spectrum, δ, ppm: 3.39 (4H,
s, CH2CN4H); 16.06 (2H, br. s, CN4H). 13C NMR spectrum, δ, ppm: 154.9 (tetrazole); 20.9 (CH2CN4H).
Found, %: C 29.11; H 3.45; N 67.22. C4H6N8. Calculated, %: C 28.92; H 3.64; N 67.44.
1,3-Di(tetrazol-5-yl)propane (3). Yield 6.1 g (73%); mp 198°C (2-propanol). IR spectrum, ν, cm-1:
1
2800-3200 (NH), 1579, 1454, 1430, 1418, 1407, 1280, 1256, 1208, 1110, 1082, 1056. H NMR spectrum,
δ, ppm (J, Hz): 2.16 (2H, q, J = 7.5, CH2CH2CN4H); 2.98 (4H, t, J = 7.5, CH2CN4H); 15.9 (2H, br. s, CN4H). 13C
NMR spectrum, δ, ppm: 155.5 (tetrazole); 24.8 (CH2CH2CN4H); 22.2 (CH2CN4H). Found, %: C 32.74; H 4.09;
N 62.27. C5H8N8. Calculated, %: C 33.33; H 4.48; N 62.19.
1,4-Di(tetrazol-5-yl)butane (4). Yield 15.3 g (87%); mp 204°C (2-propanol). IR spectrum, ν, cm-1:
2800-3200 (NH), 1578, 1457, 1448, 1424, 1321, 1305, 1260, 1204, 1127, 1109, 1085, 1053. 1H NMR spectrum,
δ, ppm (J, Hz): 1.74 (4H, q, J = 7.5, CH2CH2CN4H); 2.92 (4H, t, J = 7.5, CH2CN4H); 15.9 (2H, br. s, CN4H). 13C
NMR spectrum, δ, ppm: 155.8 (tetrazole); 26.4 (CH2CH2CN4H); 22.4(CH2CN4H). Found, %: C 36.96; H 4.93; N
57.51. C6H10N8. Calculated, %: C 37.11; H 5.19; N 57.70.
473

1,5-Di(tetrazol-5-yl)pentane (5). Yield 10.4 g (68%); mp 142°C (2-propanol). IR spectrum, ν, cm-1:
2800-3200 (NH), 1576, 1464, 1452, 1426, 1407, 1352, 1318, 1298, 1254, 1231, 1185, 1110, 1083, 1059.
1H NMR spectrum, δ, ppm (J, Hz): 1.33 (2H, q, J = 7.5, CH2CH2CH2CN4H); 1.73 (4H, q, J = 7.5,
CH2CH2CN4H); 2.87 (4H, t, J = 7.5, CH2CN4H); 15.8 (2H, br. s, CN4H). 13C NMR spectrum, δ, ppm: 155.9
(tetrazole); 27.7 (CH2CH2CH2CN4H); 26.6 (CH2CH2CN4H); 22.6 (CH2CN4H). Found, %: C 40.52; H 6.43;
N 54.38. C7H12N8. Calculated, %: C 40.38; H 5.81; N 53.81.
The work was carried out using equipment of the regional TsKP “Material knowledge and diagnostics in
advanced technologies” with the support of the Russian Fund for Fundamental Investigations
(grant 05-03-32366).
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