A kinetic study of the high temperature rearrangement of 4-ethyl-3,5-diphenyl-4H-1,2,4-triazole

Article abstract of DOI:10.1002/jhet.5570380423

The kinetics of the thermal rearrangement 4-ethyl-3,5-diphenyl-4H-1,2,4-triazoles, 1, to the corresponding 1-ethyl-3,5-diphenyl-l-alkyl-1H-1,2,4-triazoles, 2, was studied in 15-Crown-5 and octadecane at 3130 °C. The reaction was very slow in octadecane but proceed well in 15-Crown-5. The reaction order for the reaction was not constant but changed from an initial second order rate law towards a first order rate law as the reaction progressed. This was confirmed by the concentration dependent reaction order, n_c, which was larger than the time dependent rate law, n_t. The rationale for the observation was, that at high substrate concentrations the reaction order was second order while at lower concentrations a competing solvent assisted reaction plays an increasing important role. The data were in agreement with a mechanism in which the neutral 4-alkyl-triazoles in an intermolecular nucleophilic displacement reaction form a triazolium triazolate, which in a subsequent nucleophilic reaction gives the observed product.

Full text of DOI:10.1002/jhet.5570380423

Jul-Aug 2001
A Kinetic Study of the High Temperature Rearrangement
of 4-Ethyl-3,5-diphenyl-4H-1,2,4-triazole
Odd R. Gautun and Per H. J. Carlsen*
955
Department of Chemistry, Norwegian University of Science and Technology-NTNU, N-7491 Trondheim, Norway.
Received October 16, 2000
The kinetics of the thermal rearrangement 4-ethyl-3,5-diphenyl-4H-1,2,4-triazoles, 1, to the correspond-
ing 1-ethyl-3,5-diphenyl-1-alkyl-1H-1,2,4-triazoles, 2, was studied in 15-Crown-5 and octadecane at 330
°C. The reaction was very slow in octadecane but proceed well in 15-Crown-5. The reaction order for the
reaction was not constant but changed from an initial second order rate law towards a first order rate law as
the reaction progressed. This was confirmed by the concentration dependent reaction order, n , which was
c
larger than the time dependent rate law, n . The rationale for the observation was, that at high substrate con-
t
centrations the reaction order was second order while at lower concentrations a competing solvent assisted
reaction plays an increasing important role. The data were in agreement with a mechanism in which the neu-
tral 4-alkyl-triazoles in an intermolecular nucleophilic displacement reaction form a triazolium triazolate,
which in a subsequent nucleophilic reaction gives the observed product.
J. Heterocyclic Chem., 38, 955 (2001).
Introduction.
temperatures were required, making such studies difficulty to
carry out. For that reason, a previous kinetic study dealt with
reactions in melts of the pure triazoles. The results of that
study supported the rearrangement mechanism described
above. An interesting observation, however, was that
rearrangements were also taking place in the crystalline state
[5]. To get a better understanding of the details of the mecha-
nism a study of the reactions in solution was necessary.
We have reported studies of the thermal rearrangement of
neat 4-alkyl substituted 4H-1,2,4-triazoles, to the correspond-
ing 1-alkyl-1H-1,2,4-triazoles [1]. There is good evidence for
a mechanistic pathway that involve an initial bimolecular
nucleophilic displacement reaction that lead to the formation
of a "salt", a triazolium triazolate, resulting in an activation of
the triazole ring as a leaving group. Subsequent nucleophilic
attack by the triazole anion at the alkyl group positions of the
triazolium ion, yield the products. This reaction scheme is
bimolecular in nature, Scheme 1. Thus, in the 4-alkyl-substi-
tuted triazoles the heterocyclic ring behaves as a leaving
group, and give rise to products corresponding to both substi-
tution and elimination reaction pathways [2]. Previous work
excluded a concerted, unimolecular mechanism and radical
reaction. This reactivity somewhat resemble that of quater-
nary ammonium salts, which may undergo substitution as
well as elimination reactions. Recent results also appeared to
rule out any unimolecular reaction steps [3].
EXPERIMENTAL
The solvents used under the extreme conditions in this study,
was octadecane, (C H ), as a non-polar solvent and 15-Crown-5
18 38
as an example a better solvating but inert, non-nucleophilic sol-
vent. The solvents were of analytical grades and freshly distilled
prior to use. Flash points were exceeded in all experiments, and
reactions were therefore carried out in nitrogen atmosphere. Under
the reaction conditions no noticeable decompositions of the sol-
vents was observed, (GC). The triazole we have studied here was
4-ethyl-3,5-diphenyl-4H-1,2,4-triazole, 1, which rearranged to the
corresponding 1-ethyl-3,5-diphenyl-1H-1,2,4-triazole, 2.
Compounds 1 and 2 were prepared and purified as described ear-
lier [1]. These compounds were fully soluble in the solvents at 80-
90 °C in the concentration ranges applied in this study.
The anion corresponding to 3,5-diphenyl-1,2,4-triazole
is a good nucleophile, which reacts exclusively at the N-1
ring position. Reaction at the N-4 position was never
observed, neither in thermolysis reactions nor with a vari-
ety of alkylation reagents [2,4].
Instrumental Methods.
To gain further insight into the mechanistic details of this
reaction, we have conducted a kinetic study of the rearrange-
ment of 4-ethyl-3,5-diphenyl-4H-1,2,4-triazole, 1, in solu-
tion. Due to the high thermal stability of the triazoles, high
1
13
H and C NMR spectra were recorded on a JEOL JNM-
EX400 FT NMR or a JEOL FX-100 NMR spectrometer, using
CDCl as the solvent and tetramethylsilane (TMS) as the internal
standard. IR and GC-IR spectra were obtained on a Nicolet 20-
3

956
O. R. Gautun and P. H. J. Carlsen
Vol. 38
SXC FT-IR (GC Carlo Erba 5160, 25 m, CP-Sil-5 CB). Mass
spectra were recorded on a AEI MS-902 spectrometer at 70 eV
(IP) and 200 °C inlet temperature. GC measurements were per-
formed on a Varian 3700 gas chromatograph equipped with a BP-
1 capillary column (24 m).
Kinetics.
Reaction rates were determined by heating solutions of known
concentrations in the appropriate solvent, which also contained
tetracosane, (n-C H ) as an internal standard. For a kinetic
24 50
experiment, the reaction mixtures were placed in sealed capillary
tubes (1.5 x 60 mm). This operation was accomplished by placing
the tubes with the open end immersed in a heated solution (ca. 80
°C) of the substrate of known concentration, in a flask which was
then evacuate. When ambient pressure was restored by letting
nitrogen into the flask, the tubes were filled with the solution of 1
in the appropriate solvent. The filled tubes were then sealed.
-2
Slope = 1.14 x 10
r
2 = 0.973
The tubes were then placed in refluxing nonadecane, (C H ,
19 40
bp 330 °C at 1 atm), which was kept under a nitrogen atmos-
phere. At various times, sample tubes were taken out, cooled in
ice water, cleaned, crushed and the content dissolved in
dichloromethane. The composition of the mixture was deter-
mined by GC, and the amount of 1 still present and 2 formed was
measured by GC using the internal standard method. All the com-
pounds were calibrated with respect to the internal standard. In
all experiments a mass balance of better than 95 % was obtained.
Twenty tubes were used for each kinetic experiment. The ther-
molyses in 15-C-5 was carried out using 4 different concentra-
tions of 1, covering approximately one order of magnitude (1.5 x
Figure 1b. A representative example of a plot of 1 / [1] vs. time for [1]
0.0647 mol / kg.
=
o
Kinetics for the thermolysis of 1 in 15-C-5.
The results obtained for reactions in 15-C-5 is shown in Table
1. The data surprisingly appeared to agree reasonably well with
first but also with a as second order rate law. The data therefore
did not allow a clear assignment of kinetics to a reaction mecha-
nism. The reason for this apparent inconsistency may be that we
here have a kinetic system that is shifting from the one reaction
order to the other as the reaction progress. To investigate this pos-
sibility we did a further investigation of the reaction order.
-2
-2
10 - 12.8 x 10 mol / kg).
Rate Expression.
Rate data was fit to the integrated rate expressions. Thus, to
explore first order kinetics, ln [1] was plotted vs time and k was
1
determined as the slope of the straight line. For second order
Table 1
kinetics was plotted 1/[1] vs time, and the rate constant k deter-
2
mined from the slope of the line. Representative examples are
The Rate Laws for the Thermolysis of 1 at 330 °C in 15-C-5.
shown in Figures 1a and 1b respectively.
2
5
2
3
Concentration Correlated to
r
σ x 10 Correlated to
r
σ x 10
of 1.
First
Second
2
Mol/kg x 10
order rate
order rate
expression
expression
4
2
10 x k
10 x k
1
2
-1
-1
-1
(sec )
(kg mol sec )
1.57
3.53
6.47
12.8
2.78
4.17
4.01
6.56
0.966 3.2
0.986 3.1
0.994 1.7
0.995 2.5
3.79
2.20
1.14
0.99
0.894 7.7
0.977 2.1
0.984 7.8
0.987 6.2
-4
Slope = 4.01 x 10
r
2 = 0.994
The reaction-order was analysis using the differential method.,
determining the reaction order with respect to concentration, n ,
c
[6]. This was accomplished by measuring the initial rates for a
series of reactions with different starting concentrations. In a
double logarithmic plot of the log of the reaction rate versus log
of the starting concentration, the slope, of what now should be a
straight line, gives the concentration dependent reaction order, n .
c
The intercept with the y-axis corresponds to the rate constant, k .
n
The data obtained for the system here studied are shown in Table
2. The corresponding plot of log [1] vs log (d[1] /dt ) is shown
o
o
in Figure 2. A linear regression analysis shows that the data
2
points lie on a straight line (r = 0.998, σ = 0.075) with the slope
Figure 1a. A representative example of a plot of ln[1] vs. time for [1]
0.0647 mol/kg.
=
o
1.96. This is in very good agreement with a second order rate law.

Jul-Aug 2001
A Kinetic Study of the High Temperature Rearrangement
957
Table 2
The Initial Reaction Rates for Thermolysis of 1 in 15-C-5 at 330 °C
-2
-2
-2
-2
Concentration
1.57 x 10
3.53 x 10
6.47 x 10
12.8 x 10
of 1. mol/ kg
-6
-6
-5
d[1] / dt
1.00 x 10
4.02 x 10
1.41 x 10 6
o
mol/kg . sec
The intercept value of -2.50 was also in reasonable agreement the
second order rate constants reported in Table 1.
To investigate the possibility that the reaction order changed
in the course of the reaction, we also determined the reaction
order with respect to time, n . This was done by considering a
t
single run and measure the slopes of the concentration/time
graph at various times. This is equivalent to measuring the rate
for a number of reactant concentrations. The experimental data
are shown in Table 3.
Figure 3. The time dependent reaction-order, n . The log-log plot of
t
log[1] vs. log(d[1]/dt).
Slope = 1.96
R = 0.998
2
The reactions in octadecane are slow, and over time carbonation
of the starting material took place. GC measurements using inter-
nal standard showed that after 146 hours merely 37 % of the sub-
strate was left in the reaction mixtures, together with minor
amounts of the rearrangement product, but without the presence
of other reaction products. An explanation may be that at high
temperatures in non-polar solvents, alternative radical reaction
pathways may become important. For these reasons we did not
proceed further with measurements in octadecane.
Intercept = -2,50
Results and Discussion.
When the n > n it is usually interpreted that the reaction
c
t
is auto-catalytic. However, there may be an alternative
explanation that rationalizes the n > n observed in this
Figure 2. The concentration dependent reaction-order, n . The log-log plot
c
t
c
of the initial reaction rates as a function of the starting concentrations.
study. The solvent 15-C-5 solvent, being a non-polar solvent
Table 3
The Instantaneous Reaction Rate for Thermolysis of 1 in 15-C-5 at 330 °C. [1] = 12.8 x 10 mol/kg Followed to Approximately 70% conversion
-2
o
-2
-5
-2
-5
-2
-5
-2
-5
-2
-5
-2
-5
Concentration of 1. Mol / kg
d[1] / dt mol / kg . sec
10.2 x 10
6.02 x 10
6.47 x 10
4.40 x 10
4.82 x 10
3.27 x 10
3.53 x 10
2.68 x 10
2.41 x 10
2.19 x 10
1.57 x 10
1.87 x 10
1
The logarithm of the concentration was plotted vs the logarithm
has special solvating properties towards cations. In light of
the proposed initial formation of the triazolium triazolate
intermediate in the upper pathway in Scheme 1, solvation
may explain why the reaction is facile in 15-C-5 and not in
octadecane. The greater rate in 15-C-5 is consistent with the
postulated existence of a solvent stabilized ion-pair like inter-
mediate. At higher substrate concentrations, the intermediate
could be a trizolium triazolate, while at low substrate con-
centrations a 15-C-5 "oxonium" triazolate ion pair. Support
for this reaction scheme is also found in the very low reactiv-
ity in octadecane, that here is a poorly solvating solvent and
which can not participate as a nucleophile in the reaction. A
good approximation is to assume that salt formation is the
of the instantaneous rate of the reaction, i.e., log [1] vs log
t
(d[1] /dt ). This graph is shown in Figure 3. The points may fit to a
t
line with slope corresponding to a time dependent reaction order, n
t
2
= 0.64 (r = 0.988, σ = 0.051). However, we also see that the slope
for high concentrations tends to be larger than for lower concentra-
tion. This is another indication for the reaction order not being the
same all the time and that the reaction -order changes from initially
second order to first order as the reaction progress.
Kinetics for the Thermolysis of 1 in Octadecane, C H .
18 38
The reaction in this solvent were very slow even at 330 °C.
The observed data were of poor quality, and attempts to extract
meaningful rate expressions failed to yield realistic relationships.

958
O. R. Gautun and P. H. J. Carlsen
Vol. 38
rate-determining step, followed by rapid conversion of the
charged components into the neutral product. 15-C-5 has
weak nucleophilic properties, which may become apparent
under the reaction conditions described here. We therefore
assume that 15-C-5 may reacts with 1 leading to the forma-
tion of an oxonium salt as indicated in the lower pathway in
Scheme 2.
The equilibrium constant K includes the solvent con-
S,
centration as a constant. These rate expressions are in
agreement with a reaction scheme where initially the [1] -
concentration is still high, the reaction follows a second
order rate law but as 1 is consumed, the solvent assisted
reaction becomes prevalent, and the first order rate law
more important.
Cross-over Experiments.
Assuming the proposed bimolecular triazolium triazo-
late mechanism takes place, the presence of another 4-
alkyl triazole would give rise to formation of cross-over
products. This effect was observed previously on ther-
molysis of melts containing mixtures the of neat tria-
zoles [3]. However, will it also take place in solution? To
investigate this, mixtures of triazole 1 and 4-propyl-3,5-
di(4-methylphenyl)-1H-1,2,4-triazoles, 5, were ther-
molyzed in 15-C-5 solutions. Thus, a solution under
nitrogen in a sealed tube containing 34.2 mg of 1 and
46.9 mg of 5 in 1.24 g 15-C-5 was thermolyzed at 330
°C for 75 minutes. GLC analysis of the product mixture
with co-injection of authentic compounds and mass
spectrometric analysis, clearly showed that all the
expected products 2, 6, 7, 8 were formed in a
10:18:22:41 ratio as shown in Scheme 3.
This reaction scheme leads to the following rate expres-
sions, after using the steady-state approximation on ionic
intermediates 3/4 and 4/S-Et respectively.
Conclusion.
The study of the kinetics of the thermal rearrangement
4-ethyl-3,5-diphenyl-4H-1,2,4-triazoles, 1, to the corre-
sponding 1-ethyl-3,5-diphenyl-1H-1,2,4-triazoles, 2,
shows that the reactions are extremely slow in octade-
cane but proceed well in 15-C-5. Acceptable mechanistic
evidence could not be obtained in octadecane. In 15-C-5
solvent the reaction order was not constant but changed
from an initial second- to a first order rate law as the
Triazole Reaction:
2
V = K k [1]
(1)
1
2
Solvent Assisted Reaction:
V = K k [1] (2)
S
2'
Total Reaction:
2
V
= K k [1] K k [1] (3)
total
1
2
+
S 2'

Jul-Aug 2001
A Kinetic Study of the High Temperature Rearrangement
959
REFERENCES AND NOTES
reaction progressed. This was further confirmed by the
finding that the concentration dependent reaction order
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Jørgensen Molecules, 1, 242 (1996).
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411 (1994).
[3] O. R. Gautun and P. H. J. Carlsen, Eur. J. Org. Chem. 3745
(2000).
[4a] O. R. Gautun and P. H. J. Carlsen, Eur. J. Org. Chem. 3749
(2000); [b] P. H. J. Carlsen and K. B. Jørgensen, J. Heterocyclic
Chem. 34, 797 (1997).
[5] P. H. J. Carlsen, K. B. Jørgensen and O. R. Gautun, S.
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Bull. Soc. Chim. Fr. 9, 1 (1942).
n was larger than the time dependent rate law, n , an
c
t
observation normally characteristic of an auto-catalytic
reaction. However, the rationale here is that at high sub-
strate concentrations the reaction is second order in sub-
strate, while at lower concentrations a competing solvent
assisted reaction plays an increasingly important role.
Each pathway proceeds therefore through a mechanism
involving the formation of ionic intermediates. These
results corroborate and strengthen the case for the pres-
ence of triazolium ions as intermediates in the thermal
isomerization of 4-alkyl-3,5-diaryl-4H-1,2,4,-triazoles.
The proposed mechanism was further supported by the
cross-over results.