Kinetics and mechanism of formation of isomeric 1-methyl- and 2-methyl-5-vinyltetrazoles

Article abstract of DOI:10.1007/s11172-009-0293-y

The alkylation of 5-(β-dimethylaminoethyl)tetrazole (1) with dimethyl sulfate afforded 5-(β-dimethylaminoethyl)-1-methyltetrazole (2) and 5-(β-dimethylaminoethyl)-2-methyltetrazole (3). The exhaustive alkylation of compounds 2 and 3 at the terminal dimeth

Full text of DOI:10.1007/s11172-009-0293-y

Russian Chemical Bulletin, International Edition, Vol. 58, No. 10, pp. 2147—2153, October, 2009
2147
Kinetics and mechanism of formation
of isomeric 1ꢀmethylꢀ and 2ꢀmethylꢀ5ꢀvinyltetrazoles
V. A. Ostrovskii, M. E. Podkameneva, V. S. Poplavskii, and R. E. Trifonov
St. Petersburg State Institute of Technology (Technical University),
2
6 Moskovsky prosp., 190013 St. Petersburg, Russian Federation.
Fax: +7 (812) 316 2056. Eꢀmail: VA_Ostrovskii@mail.ru
The alkylation of 5ꢀ(βꢀdimethylaminoethyl)tetrazole (1) with dimethyl sulfate afforded
ꢀ(βꢀdimethylaminoethyl)ꢀ1ꢀmethyltetrazole (2) and 5ꢀ(βꢀdimethylaminoethyl)ꢀ2ꢀmethyltetrꢀ
5
azole (3). The exhaustive alkylation of compounds 2 and 3 at the terminal dimethylamino
group gave 1ꢀmethylꢀ (4) and 2ꢀmethylꢀ5ꢀ(βꢀtrimethylammonioethyl)tetrazole (5) methyl sulꢀ
fates. The proton elimination from the αꢀmethylene (with respect to the tetrazole cycle) groups
of the quaternary ammonium cations of salts 4 and 5 by the action of a base leads to the
corresponding zwitterions 4± and 5 , which in the rateꢀdetermining step undergo the cleavage
of the nitrogen—carbon bond with the formation of 1ꢀmethylꢀ5ꢀvinylꢀ (6) and 2ꢀmethylꢀ5ꢀ
±
±
vinyltetrazole (7). The true constant of the transformation of zwitterion 4 into tetrazole 6 is
±
2
1 times higher than that for the transformation of zwitterion 5 into tetrazole 7.
Key words: 1ꢀmethylꢀ5ꢀvinyltetrazole, 2ꢀmethylꢀ5ꢀvinyltetrazole, kinetics of formation,
deamination mechanism.
Isomeric Nꢀalkylꢀ5ꢀvinyltetrazoles are initial monoꢀ
mers in the synthesis of the corresponding poly(vinylꢀ
tetrazoles), which are promising highꢀenergy polymers
Scheme 1
1
with a series of unique properties. Beginning from the
1
960s chemists are searching for efficient methods of synꢀ
2
thesis of Nꢀalkylꢀ5ꢀvinyltetrazoles. This search is impedꢀ
ed by numerous quantitative studies of key chemical proꢀ
cesses resulting in 5ꢀvinyltetrazole derivatives. The results
on studying the kinetics of alkylation of NHꢀunsubstituted
5
ꢀvinyltetrazole with methyl iodide in an acetonitrile meꢀ
3
dium in the presence of triethylamine have recently been
published. The hypothetical mechanism was formulated
3
and the boundaries for changing the reaction conditions,
which allow one to control the rate and selectivity of alkyꢀ
lation in certain limits, were determined. However, since
the initial substrate is NHꢀunsubstituted 5ꢀvinyltetrazole
is a hardly accessible compound yet, the patented method
for the preparation of Nꢀalkylꢀ5ꢀvinyltetrazoles based on
the synthesis and subsequent alkylation of 5ꢀ(βꢀdimethylꢀ
aminoethyl)tetrazole with dimethyl sulfate in an aqueous
medium in the presence of alkaline metal hydroxide seems
4
,5
more promising. The variants of this method described
in the cited patents are almost identical and only differ by
the nature of the base used: NaOH (see Ref. 4) and KOH
(
see Ref. 5), respectively. Let us consider the hypothetical
sequence of the synthesis of isomeric Nꢀmethylꢀ5ꢀvinyltetrꢀ
4
,5
azoles postulated in the patents (Scheme 1).
Isomeric vinyltetrazoles 6 and 7 are formed due to the
deamination of intermediate quaternary ammonium salts
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2082—2088, October, 2009.
066ꢀ5285/09/5810ꢀ2147 © 2009 Springer Science+Business Media, Inc.
1

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Ostrovskii et al.
4
and 5 occurring under the action of a strong base. Note
(monitoring with a pHꢀmeter) by the dropwise addition of a 15%
aqueous solution of KOH. Then a 15% solution of potassium
hydroxide (~100 mL) until pH = 13 was achieved. The obtained
aqueous solution was primarily extracted with carbon tetrachloꢀ
ride (4×50 mL). The joined extract was dried with anhydrous
that 5ꢀ(βꢀdimethylaminoethyl)tetrazole (1) has first been
isolated, identified, and studied 30 years after the publicaꢀ
tion of the above cited patents. Naturally, the synthesis of
substrate 1 and all subsequent transformations were carꢀ
6
MgSO . The solvent was distilled in vacuo. Tetrazole 3 was obꢀ
4
,5
4
ried out in situ, under the oneꢀpot conditions without
isolation and identification of intermediates 2—5. It should
also be noted that the monoꢀ and exhaustive alkylations
tained in a yield of 9 g (14%) as an oily colorless liquid with the
characteristic odor of amines. Tetrazole 2 was synthesized acꢀ
cording to an analogous procedure. However, methylene chloꢀ
ride (4×50 mL) was used instead of CCl4 for the secondary
extraction of an aqueous reaction solution. Tetrazole 2 was
obtained in a yield of 8 g (13%) as an oily colorless liquid with
the characteristic amine odor. Tetrazoles 1 and 3 were immediꢀ
ately used for the synthesis of the corresponding methyl sulfates
(
see Scheme 1) were carried out5,6 at high pH (~13). Eviꢀ
dently, it is difficult to judge about the mechanism of the
key steps and optimal conditions of particular steps of the
synthesis of vinyltetrazoles 6 and 7 on the basis of availꢀ
able data.
The purpose of the present work is the synthesis of
individual quaternary ammonium salts 4 and 5 and the
study of deamination processes of each key intermediate
product leading to the formation of 1ꢀmethylꢀ (6) and
4
and 5 by exhaustive alkylation with dimethyl sulfate in carbon
tetrachloride.
1
ꢀMethylꢀ5ꢀ(βꢀtrimethylammonioethyl)tetrazole methyl sulꢀ
fate (4). Tetrazole 2 (9 g, 0.058 mol) was emulsified in СCl4
(50 mL). Dimethyl sulfate (5.5 mL, 0.058 mol) in CCl (25 mL)
4
2ꢀmethylꢀ5ꢀvinyltetrazoles (7) in a wide pH range.
was added dropwise to the resulting emulsion with vigorous stirꢀ
ring (20 °C). The colorless crystalline precipitate that formed
was filtered off, thoroughly washed on the filter with СCl , and
dried in an air flow. Compound 4 was obtained in a yield of 12.5 g
4
Experimental
(
80%) as colorless fine crystals with m.p. 141 °C (decomp.).
The UV absorption spectra were recorded on a Shimadzu
Found (%): С, 34.6; H, 6.55; N, 25.1. M, 281 (inverse ebulliosꢀ
copy). C H N O S. Calculated (%): С, 34.2; H, 6.82; N, 24.93.
UVꢀ2401 PC spectrophotometer equipped with the temperaꢀ
8
1
19
5
4
1
tureꢀmaintained cell holder (T±0.02 °C). The H NMR spectra
M, 281. H NMR (D O), δ: 3.4 (s, 9 H, Me N); 3.8 (t, 2 H,
2
3
were measured on a Bruker WMꢀ400 spectrometer (400 MHz).
The internal standard was HMDS. The pH monitoring of the
reaction solutions was carried out with an Eurotech CyberScan
pHꢀ510 pHꢀmeter.
αꢀCH , J = 6 Hz); 3.8 (s, 3 H, SO Me); 4.0 (t, 2 H, βꢀCH ); 4.1
(s, 3 H, N(1)Me (tetrazole)).
2ꢀMethylꢀ5ꢀ(βꢀtrimethylammonioethyl)tetrazole methyl sulꢀ
fate (5) was synthesized similarly by the alkylation of tetrazole 3
2
4
2
5
ꢀ(βꢀDimethylaminoethyl)tetrazole (1) was synthesized and
in a CCl solution. The yield was 13.8 g (84%), colorless crystals,
m.p. 148 °C (decomp.). Found (%): С, 34.42; H, 7.01; N, 25.28.
4
6
purified according to a described procedure. Dimethyl sulfate
was purified by distillation in vacuo. Only freshly distilled diꢀ
methyl sulfate was used in all experiments by monitoring only the
refractive index nD20 = 1.3874. Potassium hydroxide (reagent
grade) was used without additional purification. Solutions for
spectrophotometric measurements and kinetic experiments were
prepared from bidistilled water. The activity values of hydrogen
ions for aqueous solutions of potassium hydroxide provided
for kinetic measurements were established experimentally
up to pH (H_) = 13. Aqueous solutions of KOH characterized
by the acidity functions H_ > 13 were prepared as shown below
M, 273 (inverse ebullioscopy). C H N O S. Calculated (%):
8
19
5
4
1
С, 34.20; H, 6.82; N, 24.93. M, 281. H NMR (D O), δ: 3.4 (s, 9 H,
2
Me N); 3.70 (t, 2 H, αꢀCH , J = 6 Hz); 3.8 (s, 3 H, SO Me);
3
2
4
4.0 (t, 2 H, βꢀCH ); 4.5 (s, 3 H, N(2)Me (tetrazole)).
2
1ꢀMethylꢀ (6) and 2ꢀmethylꢀ5ꢀvinyltetrazoles (7) were synꢀ
3
thesized and purified by a known method. The properties of
3
—5
compounds 6 and 7 correspond to the published data.
Vinylꢀ
tetrazole 6, b.p. 116—119 °C (1 Torr), nD20 = 1.5025. H NMR
1
(D O), δ: 3.88 (s, 3 H, Me); 5.67, 6.01, 6.53 (s, 3 H, vinyl).
2
2
0
1
Vinyltetrazole 7, b.p. 80 °C (20 Torr), nD = 1.4850. H NMR
(
see procedure of kinetic measurements) on the basis of the
(D O), δ: 4.11 (s, 3 H, Me); 5.48, 6.18, 6.60 (3 H, vinyl).
2
7
tabulated data given in the classical review. Sample data of
KOH concentrations in water and the corresponding acidity
Spectrophotometric measurements. The UV spectra were
measured in water. They differ substantially for quaternary amꢀ
monium salts 4 and 5, on the one hand, and the corresponding
vinyltetrazoles 6 and 7, on the other hand (Fig. 1). In particular,
rather high molar absorption coefficients of the bands in the
spectra of isomeric vinyltetrazoles 6 and 7 correspond to the
π → π* transitions. The steric interaction of the methyl and vinyl
groups taking place only in the case of vinyltetrazole 6 somewhat
7
–1
functions, cKOH/mol L (H_): 0.1 (13.0), 0.8 (14.0), 3.5 (15.0),
can be indicated as an example that clarifies the procedure of
preparation of aqueous solutions with the specified pH (H_)
value. Testing experiments confirm good (±0.05 pH units)
agreement between the tabulated acidity functions H_ and
the boundary, accessible for experimental determination pH
1
(
2
(
12—13) values. The procedures of synthesis of intermediates
—5 were developed on the basis of the original chemical scheme
Scheme 1) with necessary modifications (see Results and
Discussion).
worsens the πꢀelectron conjugation. For this reason, the ε value
at the absorption band maximum of tetrazole 6 is somewhat
lower than that for vinyltetrazole 7. The analytical concentraꢀ
–
4
–1
tions of methyl sulfates 4 and 5 were 1—2•10 mol L and
those for vinyltetrazoles 6 and 7 were 3—5•10–5 mol L–1. The
Bouguer—Lambert—Beer law was fulfilled in the working conꢀ
centration range for compounds 4—7.
5
ꢀ(βꢀDimethylaminoethyl)ꢀ1ꢀmethyltetrazole (2) and 5ꢀ(βꢀdiꢀ
methylaminoethyl)ꢀ2ꢀmethyltetrazole (3). Dimethyl sulfate
(
39.8 mL, 0.42 mol) was added dropwise with stirring (20 °C) to
a solution of tetrazole 1 (56 g, 0.4 mol) in water (200 mL). The
solution was stirred for 5 h at ~20 °C, maintaining pH = 6—7
The kinetics of deamination of methyl sulfates 4 and 5 was
monitored using the spectrophotometric method by the accuꢀ

Formation of isomeric methylvinyltetrazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
2149
ε
Table 1. Apparent rate constants for the deamination of methyl
sulfates 4 and 5 at different pH values of an aqueous solution of
KOH at 20 °C
4
1
0000
3
2
Methylꢀ
sulfate
рН
kapp•105
/s–1
Methylꢀ
sulfate
рН
kapp•105
/s–1
8
6
4
2
000
000
000
000
(H_)
(H_)
4
8.30
0.44
4.07
5.01
5
12.27
12.53
12.73
12.80
13.06
13.20
13.60
13.76
13.91
14.00
14.30
14.60
14.90
15.20
15.50
15.80
3.98
7.41
11.70
17.80
19.10
9
9
9
.31
.42
.63
8.10
1
9.96
0.10
10.48
0.83
1.24
1.48
17.80
24.50
66.10
105.00
316.00
724.00
0.13
0.25
0.80
1.02
1.95
1
38.00
74.10
2
00
210
220
230
240
λ/nm
1
1
1
112.20
138.00
158.00
174.00
239.00
302.00
316.00
310.00
316.00
Fig. 1. UV spectra in water at 20 °C: 1, 1ꢀmethylꢀ5ꢀ(βꢀtrimethylꢀ
ammonioethyl)tetrazole methyl sulfate (4), с = 1.82•10–4 mol L
–1
,
λmax = 198 nm; 2, 2ꢀmethylꢀ5ꢀ(βꢀtrimethylammonioethyl)tetrꢀ
5
10.65
ꢀ
4
–1
azole methyl sulfate (5), с = 1.52•10 mol L , λmax = 205 nm;
1
1
1
1
1
1.10
1.50
1.71
2.00
2.03
–
5
–1
3
, 1ꢀmethylꢀ5ꢀvinyltetrazole (6), с = 4.23•10 mol L , λmax =
220 nm; 4, 2ꢀmethylꢀ5ꢀvinyltetrazole (7), с = 3.31•10 mol L ,
–5
–1
=
λmax = 215 nm.
2.24
mulation of the reaction products, viz., vinyltetrazoles 6 and 7,
respectively. The current absorbances of the reaction product
were detected at the analytical wavelength close to the absorpꢀ
tion maximum (see Fig. 1).
Results and Discussion
Determination of the apparent rate constants for the deamiꢀ
nation of methyl sulfates 4 and 5. A weighed sample of methyl
sulfate 4 or 5 (0.02 g) was dissolved in water in a 50ꢀmL volumetꢀ
ric flask, after which the level of the solution was brought to the
filling mark. An aliquot of the obtained solution (1 mL) was
diluted in a 25ꢀmL volumetric flask with an aqueous solution of
KOH of such a concentration that the pH value of the resultꢀ
ant solution would correspond to a specified value. The reꢀ
quired concentration of potassium hydroxide in water, providing
pH (H_) > 13, was determined as described above on the basis of
For the purpose of the present work, it was necessary
to isolate individual quaternary ammonium salts 4 and 5
from the reaction solution and to study their reactivity.
Under the conditions given in patents (dimethyl sulfate
excess, pH ≈ 13), the processes of monoalkylation of the
tetrazole cycle of tetrazole 1 and exhaustive alkylation of
the terminal dimethylamino groups in compounds 1—3
occur simultaneously. Moreover, in addition to the exꢀ
haustive alkylation of the dimethylamino group of subꢀ
strates 2 and 3, intermediate quaternary ammonium salts
4
,5
7
the published data. The moment of mixing in the volumetric
flask of two components, namely, an aliquot of an aqueous soluꢀ
tion of the corresponding of methyl sulfate (4 or 5) and an aqueꢀ
ous solution of KOH, was accepted as the time of reaction onset.
A portion of the reaction solution was placed in the working cell
of the spectrophotometer, whereas the comparison cell was filled
with an aqueous solution of KOH with the same concentration
as in the working cell. The apparent rate constant of the first
order was calculated by the equation
4
and 5 are deaminated to form isomeric vinyltetrazoles 6
and 7 (see Scheme 1). Evidently, no intermediate prodꢀ
ucts cannot be isolated under similar dynamic conditions.
6
Based on the previously published data, we assumed that
at pH 6—7 of the reaction solution both the tetrazole
cycle (pK = 3.9) and the terminal dimethylamino group
a
(pKBH+ = 9.4) of tetrazole 1 exist in the ionized forms.
Therefore, at pH 6—7 the predominant monoalkylation of
the bipolar ion 1 should occur at the endocyclic nitrogen
kapp = (2.303/τ)lg[(D – D )/(D – D )],
0
∞
τ
∞
±
where D and D are the absorbances at the initial and current
atoms of tetrazolide with the formation of isomeric
Nꢀmethyltetrazoles 2H+ and 3H+ isomeric at the diꢀ
methylamino group (Scheme 2).
Based on this assumption, we carried out the monoꢀ
alkylation of tetrazole 1 with dimethyl sulfate* in an aqueꢀ
ous solution of KOH at pH 6—7. Indeed, after the
monoalkylation ceased and pH increased subsequently to
0
τ
time moments (τ), respectively; D is the absorbance of the reacꢀ
∞
tion product. The reaction order was confirmed by the differenꢀ
tial method.8 Linearity of the semilogarithmic anamorphoses
(
dependences of log(D – D ) on τ) obeyed up to the high (highꢀ
0
∞
er than 80%) conversion of the reactants. The arithmetical
average obtained as a result from three to five parallel entries
was taken as the rate constant value. The determination error of
the apparent rate constants did not exceed 5—7 rel.%.8 The
apparent rate constants for the deamination of methyl sulꢀ
fates 4 and 5 in aqueous solutions of potassium hydroxide are
listed in Table 1.
* A minor (~5 mol.%) excess of the alkylating agent over subꢀ
strate 1 was used with allowance for the parallel hydrolysis of
dimethyl sulfate.

2150
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Ostrovskii et al.
Scheme 2
Salts 4 and 5 were obtained by the action of dimethyl
sulfate in carbon tetrachloride in which the both reaction
products, the corresponding isomeric methyl sulfates 4
and 5, are almost insoluble.
The result of this experiment opened a way to the quanꢀ
titative study of the synthesis of isomeric vinyltetrꢀ
azoles 6 and 7.
According to the original patents,4,5 vinyltetrazoles 6
and 7 are formed due to the decomposition of the correꢀ
sponding quaternary ammonium based formed from salts
4
and 5 in an alkaline medium (see Scheme 1). In fact,
upon the dissolution of methyl sulfates 4 and 5 in an aqueꢀ
ous solution of KOH (pH 13) we observed very fast and
(
according to the spectrophotometric data) quantitative
Reaction conditions: (MeO) SO , pH 6—7.
2
2
formation of vinyltetrazoles 6 and 7. Taking into account
the known data on the kinetics and mechanism of proꢀ
cesses of Hoffmann´s cleavage of various quaternary amꢀ
monium bases (see, e.g., Ref. 9), we describe the transforꢀ
mations of 1ꢀmethylꢀ (4 ) and 2ꢀmethylꢀ5ꢀ(βꢀtrimethylꢀ
ammonioethyl)tetrazole (5 ) cations into the correspondꢀ
1
3 (the dimethylamino group transformed into the "free"
state), tetrazoles 2 and 3 were isolated from the reaction
solution by extraction. The choice and sequence of solꢀ
vents for the selective extraction from the reaction soluꢀ
tion of compounds 2 and 3 are caused by substantial difꢀ
ferences in polarities of the regioisomers: the dipole moꢀ
ments of 1,5ꢀdisubstituted tetrazoles are ~2 times higher
than those for the corresponding 2,5ꢀdisubstituted tetrꢀ
+
+
ing vinyltetrazoles 6 and 7 by Scheme 3.
The acidic dissociation of the αꢀmethylene (with reꢀ
+
+
spect to the tetrazole cycle) groups of cations 4 and 5
occurs under the action of a base. The formed zwitterions
4 and 5 undergo the cleavage of the nitrogen—carbon
bond (βꢀcleavage) with the formation of trimethylamine
(deamination) and the corresponding olefins 6 and 7. The
quantitative measure of Brönsted CHꢀacidity of cations
1
±
±
azoles. Therefore, the solvent with low polarity, viz., CCl ,
4
was used for the isolation of tetrazole 3, whereas methylꢀ
ene chloride was used for the subsequent extraction of
tetrazole 2. Unfortunately, we failed to completely identiꢀ
fy tetrazoles 2 and 3 because of their high hygroscopicity.
At the same time, the nature of intermediates 2 and 3 is
indirectly confirmed by the result of their exhaustive alkylꢀ
ation at the dimethylamino group. The low yield of comꢀ
pounds 2 and 3 isolated from the corresponding joined
extracts is due to the high solubility of these secondary
amines in the aqueous phase. However, in the context of
the above formulated purpose of this study, the yield of
amines 2 and 3 is not a basic factor. It is important that
this experiment has opened the way for the subsequent
synthesis of products of the exhaustive alkylation of salts 4
and 5 and quantitative investigation of their reactivity.
+
+
4
4 and 5 is given by the corresponding constants K and
5
a
4
K . The measure of the reactivity are the true rate k´ and
a
5
k´ for the deamination—βꢀcleavage of the corresponding
±
±
zwitterions 4 and 5 .
An analysis of the apparent rate constants is consistent
4
with Scheme 3. The apparent rate constants k
and
app
5
kapp increase substantially with an increase in the pH of
the reaction solution (see Table 1). The dependences of
logkapp on pH for the reactions of compound 4 in the
range of pH 8.3—11.2 (n = 10) and compound 5 in the
range of pH (H_) 10.6—14.3 (n = 16) are linear (Fig. 2).
This is also indicated by high correlation coefficients and
Scheme 3

Formation of isomeric methylvinyltetrazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
2151
log4kapp = log( k´ K ) – log(a + K ),
4
4
H+
4
(6)
(7)
logkapp
a
a
1
log5kapp = log( k´ K ) – log(a + K ).
5
5
5
–
–
–
–
–
2
3
4
5
6
H+
a
a
2
Let us monitor the influence of boundary conditions
using Eq. (7) as an example. For instance, for relatively
5
low pH values of the reaction solution ( K << a ) Eq. (7)
H+
a
is transformed into the correlation
log5k
app
5
5
= pH + log( k´ K ).
(8)
a
Therefore, at moderate pH values the dependence of
log5kapp vs pH is a linear regression with the slope ratio
equal to unit. On the contrary, at rather high pH values,
especially for the acidity of the medium described by the
9
10
11
12
13 14
15 pH (H_)
Fig. 2. Dependences of logarithms of the apparent rate constant
for deamination in an aqueous solution of KOH on pH (Н_) at
H_ function (aH
+
<< K ), Eq. (7) is transformed into the
a
2
0 °C: 1, 1ꢀmethylꢀ5ꢀ(βꢀtrimethylammonioethyl)tetrazole meꢀ
simple equality
thyl sulfate (4) and 2, 2ꢀmethylꢀ5ꢀ(βꢀtrimethylammonioethyl)ꢀ
tetrazole methyl sulfate (5).
5
5
kapp = k´.
(9)
In fact, in the region of moderate pH values the regression
equations (2) and (3), characterizing the deamination proꢀ
relatively low standard deviations characterizing the corꢀ
responding regression lines (Eqs (2) and (3)).
±
±
cesses of zwitterions 4 and 5 , are linear and the slope
ratio is equal (for Eq. (2)) or close (for Eq. (3)) to unity.
As already mentioned above, the asymptotic region of
the dependence corresponding to equality (9) was experiꢀ
log4kapp = (1.00±0.02) pH – (13.73±0.21)
r = 0.99, n = 10, s = 0.06)
(2)
(
±
mentally detected for the deamination of zwitterion 5 in
log5kapp = (1.02± 0.02) pH – (16.85±0.14)
r = 0.99, n = 16, s = 0.10)
(3)
the region H_ > 14.5 (see Fig. 2). It follows from this that
±
the true rate constant for the deamination of substrate 5 ,
(
which is numerically equal to the apparent rate constant
5
–3 –1
At H_ > 14 the asymptotic region is observed (see Fig. 2)
value (see Fig. 2), is k´ = 3.11•10
s
(20 °C). Inserting
5
5
in the plot of log k vs pH (H_) for the reaction of zwitꢀ
the value of the true rate constant k´ into the product
k´ K (8) and equalizing the obtained product to the nuꢀ
merical value of the free term of the regression (3), we
obtain the equation with one unknown, whose solution
gives the CHꢀacidity function of ion 5 : р K = 14.3
(20 °C). As mentioned above, the limiting value k = k´
cannot be determined by a similar way because of too high
deamination rate. Therefore, it is impossible to calculate
the CHꢀacidity function of ion 4 (р K ) by the above
described algorithm. That is why we used an alternative
procedure. Postulating that the true rate constants k´ and
the CHꢀacidity constants K are independent of the acidꢀ
ity (basicity) of the medium (i.e., they remain constant
under the experimental conditions), we may write the folꢀ
lowing equations
app
±
5
5
terion 5 formed due to the acidic dissociation of tetrazole
a
cation 5+ (see Scheme 3). This character of the depenꢀ
dence of logarithms of the apparent rate constants on pH
is typical of the baseꢀcatalyzed reactions10 and, in our
case, is caused by the shift to the right of the equilibrium
+
5
a
4
4
app
+
←
±
5
→ 5 (see Scheme 3). As can be seen from Fig. 2, we
failed to detect experimentally a similar asymptotic region
4
±
4
for the plot of log k vs pH (H_) because of the high rate
app
a
±
of cleavage of zwitterion 4 . Nevertheless, it can be asꢀ
4
sumed that this region exists in the region pH (H_) > 12.
4
Thus, one more specific feature of the studied processes
a
4
5
can be noted: at the same pH values k
>> k
(see
app
app
Table 1, Fig. 2). For the analytical confirmation of the
above formulated hypotheses for the processes of cleavage
±
±
of zwitterions 4 (4) and 5 (5) that relate the apparent
4
ki (ai + K ) = k´ K ,
4
4
4
H+
(10)
(11)
app
a
a
and true rate constants
4kj (aj + K ) = k´ K
4
4
4
4
4
4
4
app H+
a
a
kapp(aH
+
+ K ) = k´ K ,
(4)
(5)
a
a
for two different arbitrarily chosen values of the acidity of
the medium (aiH+, a H+).
5kapp(a + K ) = k´ K
5
5
5
j
H+
a
a
The combined solution of Eqs (10) and (11) results in
the correlation
(
aH+ is the activity of the hydrogen ion (acidity of the
medium)), let us consider Eqs (6) and (7), which were
derived on the basis of Scheme 3 with allowance for the
principle of stationarity.11 These equations are logarithꢀ
mic forms of Eqs (4) and (5).
4
4
j
ajH+ – 4ki
aiH+)/(4ki – 4kjapp),
app
K = ( k
(12)
a
app
app
4
in which the single unknown is the desired K value.
a

2152
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Ostrovskii et al.
1
9
In order to check the applicability of Eq. (12) for the
molecular processes). This fact indicates the high degree
of solvation of the polar activated complexes. It is known9
that Hoffmann´s cleavage in such polar solvents as water
4
quantitative estimation of K , we approved this algorithm
a
5
for the calculation of the K constant, whose value has
a
+
previously been found by another method. For this purꢀ
often proceeds via the E2 mechanism. The NMe subꢀ
3
5
pose we chose from Table 1 a couple of k values and
stituent exerting a strong induction (–I) effect favors proꢀ
ton elimination from the carbon atom of the methylene
group to form the corresponding zwitterion. As a whole,
the values of the kinetic and activation parameters do not
contradict the above advanced hypothesis, according to
which vinyltetrazole 7 is formed due to the cleavage in the
Hoffmann reaction (deamination) of zwitterion 5± (see
Scheme 3). It can be assumed that this mechanism also
app
the corresponding couple of the a
+
values.
H
i
5
= 8.0•10–6 s–1 and
The apparent rate constants k
app
5kj
= 1.12•10
–3
s
–1
(see Table 1) correspond to the
app
i
–12
chosen values of pH = 11.5 (a
H+
= 3.16 10 ) and 13.76
j
–14
(
a
H+
= 1.74•10 ). The insertion of these couples into
the formula analogous to Eq. (12) results in the following
5
–15
5
CHꢀacidity constant: K = 5.032•10
(р K = 14.3
a
a
±
(
20 °C)), which coincides with the value calculated from
occurs for the deamination of zwitterion 4 .
the free term of regression (3). Similarly, when choosing
the couples of pH (aH+) and k values (see Table 1), we
To conclude it should be noted that the regularities
revealed in this work can form a basis of the rational methꢀ
od for the synthesis of isomeric vinyltetrazoles 6 and 7,
which are practically important. The differences in the
rate constants of transformation of isomeric substrates 4
and 5 are so high that the deamination process can be
carried out consequently by a stepped increase in the pH
of the reaction medium. For example at pH 9—10 (see
Fig. 2) methyl sulfate 4 reacts, being substantially more
reactive in this pH range. In this case, only vinyltetrazole
6 is formed and isolated from the reaction solution by
extraction with methylene chloride. The subsequent inꢀ
crease in the basicity of the medium to pH ≈ 13 activates
the formation of vinyltetrazole 7, which is isolated from
the solution by extraction with the same solvent. Evidentꢀ
ly, the method developed with account for this recomꢀ
mendation is very promising as an elegant and efficient
replacement of vacuum distillation, which has been used
to presently for the separation and purification of isomeric
4
app
4
used the same procedure for the calculation of the K and
k´ values. The calculated values of the CHꢀacidity conꢀ
stant of ion 4 and the true rate constant for deamination
of zwitterion 4 were as follows: р K = 12.6 (20 °C) and
(20 °C). As can be seen from these
data, the tetrazole cation 4 is a stronger CHꢀacid than
the tetrazole cation 5 . Perhaps, the reason for the higher
CHꢀacidity of ion 4 compared to that of ion 5 is that the
induction effect (–I) manifested by the polar tetrazolꢀ1ꢀyl
group is stronger than that of the tetrazolꢀ2ꢀyl substituent.
The difference in electronic effects of the heterocyclic subꢀ
stituents, most likely, determines the ratio of reactivities
a
4
+
±
4
a
4
–2 –1
k´ = 6.60•10
s
+
+
+
+
±
±
of the isomeric substrates 4 and 5 . The ratio of the true
deamination rate constants (20 °C) has the following form:
4
5
k´ = 21 k´.
As a whole, the data obtained confirm the hypothesis
see Scheme 3) for the mechanism of formation of vinylꢀ
(
2
,3
tetrazoles 6 and 7. An additional information about the
mechanism of the processes studied can also be obtained
by an analysis of the activation parameters of the deamiꢀ
nation of substrates 4± and 5±. It should be taken into
vinyltetrazoles.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ08ꢀ00483ꢀa)
and the Council on Grants of the President of the Russian
Federation (Program for State Support of Young Scienꢀ
tistꢀDoctors of Science, Grant MDꢀ1818.2008).
account that the determination of the activation parameꢀ
ters of the reactions promoted by acids or bases is difficult:
only the true rate constants should correctly be used for
this purpose. In this work, we managed to determine the
activation parameters only for the reaction involving meꢀ
References
5
thyl sulfate 5. For this purpose, the true rate constants k´
were determined from the asymptotic regions of the kinetꢀ
ic profiles (log k´—рН) plotted at different temperatures
1
. V. A. Ostrovskii, G. I. Koldobskii, R. E. Trifonov, Compr.
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5
(
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5
(13)
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1
(
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#
2
4
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#
–1 –1
entropies (ΔS = –7 J mol
K ) were calculated from
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1
2
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8
. C. H. Rochester, Acidity Functions, Academic Press, Lonꢀ
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. H. G. O. Becker, Einführung in die Elektronentheorie Orgaꢀ
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1
0. K. J. Laidler, Reaction Kinetics, Pergamon Press, Oxford—Lonꢀ
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don—New York—Paris, 1963.
in revised form August 25, 2009