Synthesis, structure, and isomerism of N-2,4-dinitrophenylbenzotriazoles

Article abstract of DOI:10.1016/j.tet.2007.02.083

Both isomers of N-(2′,4′-dinitrophenyl)benzotriazole, the 1(3)- and the 2-substituted, have been characterized and their reciprocal isomerism was studied. Cross-experiments in the presence of 5(6)-nitro-1H-benzotriazole proved that the isomerization of 2-(2′,4′-dinitrophenyl)-2H-benzotriazole into the 1-isomer occurs by an intermolecular mechanism. The reported reaction of 5(6)-nitro-1H-benzotriazole with 1-chloro-2,4-dinitrobenzene has been reexamined discovering that there is an error in the proportions of N-substituted isomers. A possible explanation for the observed isomerizations was proposed. Identification of all compounds by multinuclear magnetic resonance, including solid-state studies, has been achieved.

Full text of DOI:10.1016/j.tet.2007.02.083

Tetrahedron 63 (2007) 3737–3744
Synthesis, structure, and isomerism of N-2,4-
dinitrophenylbenzotriazoles
a,
M. Dolores Santa Marıa, Rosa M. Claramunt, M. Angeles Garcıa and Jose Elguero
a,
a
b
ꢀ
*
*
ꢀ
ꢀ
ꢀ
aDepartamento de Quꢀımica Orgaꢀnica y Bio-Orgaꢀnica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
b
´
Instituto de Quꢀımica Medica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain
Received 5 December 2006; revised 13 February 2007; accepted 20 February 2007
Available online 23 February 2007
Dedicated to Professor Guy Ourisson in memoriam
Abstract—Both isomers of N-(20,40-dinitrophenyl)benzotriazole, the 1(3)- and the 2-substituted, have been characterized and their reciprocal
isomerism was studied. Cross-experiments in the presence of 5(6)-nitro-1H-benzotriazole proved that the isomerization of 2-(20,40-dinitro-
phenyl)-2H-benzotriazole into the 1-isomer occurs by an intermolecular mechanism. The reported reaction of 5(6)-nitro-1H-benzotriazole
with 1-chloro-2,4-dinitrobenzene has been reexamined discovering that there is an error in the proportions of N-substituted isomers. A pos-
sible explanation for the observed isomerizations was proposed. Identification of all compounds by multinuclear magnetic resonance, includ-
ing solid-state studies, has been achieved.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
by cyclization of the mono-(20,40-dinitrophenyl)-o-phenyl-
enediamine with nitrous acid.4,5 Afterward, compounds 3
and 4 have been published several times,6–12 but only
Davydov et al.8 have described again the formation of both
isomers, 1-(20,40-dinitrophenyl)-1H-benzotriazole (3) and
2-(20,40-dinitrophenyl)-2H-benzotriazole (4).
In 1966–1967 three groups studied simultaneously the reac-
tion between 1H-benzotriazole (1) and 1-halo-2,4-dinitro-
benzenes (2) (Scheme 1).1–3 Some of us carried out the
reaction of 2a and 1 in xylene at reflux and obtained exclu-
sively the 1-isomer 3.2 On the other hand, Kamel et al. carried
out the reaction of 2b and 1 in ethanol in the presence of so-
dium acetate obtaining both isomers 3 and 4 in a 70:30 ratio.3
Wilshire1 also did the reaction of 2a and 1 in a variety of sol-
vents and reported that the ratio of 3/4 is 98:2 in benzene and
74:26 in ethanol, the highest proportion of 4 being obtained in
DMF (62:38 ratio). The 1-isomer 3 has long been known
since Borsche and Rantscheff prepared it (mp 186–187 ꢀC)
We have summarized in Table 1 all the results reported so far
on these two compounds.
In view of the inconsistency in the melting points reported
in Ref. 8 and, especially, the result that a reaction of N-aryl-
ation is so dependent of the experimental conditions varying
from pure 3 to pure 4 (even assuming that minute quantities
X
O2N
3
4
See Table 1
NO2
3a
N
N
N
N
5
6
for conditions
+
+
N2
N
NO2
N
N1
1'
7a
6'
N
7
2' NO2
H
NO2
4
3'
1
2, a, X = F
b, X = Cl
c, X = Br
5'
4'NO2
3
Scheme 1. Formation of dinitrophenylbenzotriazoles (3 is represented in the Z conformation with the nitro group pointing toward the N2 of the benzotriazole).
We have extended the E/Z nomenclature to the conjugate N1-aryl single bond.
Keywords: Benzotriazoles; 2,4-Dinitrophenyl group migration; Kinetics; NMR; GIAO/B3LYP/6-31G* absolute shieldings; B3LYP/6-31G** stabilization
energies.
* Corresponding authors. Tel.: +34 913987 322; fax: +34 913988 372; e-mail addresses: dsanta@ccia.uned.es; rclaramunt@ccia.uned.es
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.083

3738
M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
Table 1. Literature results on benzotriazole derivatives 3 and 4
Entry
1
2, X
a, F
Conditions
Isomer 1-R 3
Isomer 2-R 4
Ref.
1
3/4 ratio
NMR
1H
Diff. solv., rt
185–187 ꢀC
167–168 ꢀC
98:2a
74:26b
>99
70:30
>99
<0.01
76:19d
>99
2
3
4
5
6
7
8
9
10
a, F
Xylene, reflux
EtOH, reflux
Toluene, reflux
DMSO/NaH/rt
PTC
Cs2CO3, DMF, rt
PTC; MW
Ionic liquid
182–183 ꢀC
186 ꢀC
—
165 ꢀC
—
2
1H
None
b, Cl
b, Cl
c, Br
b, Cl
a, F
b, Cl
b, Cl
This work
3,12
6,12
7
8
9
10
11
—
182–184 ꢀC
—
1H
166–167 ꢀCc
1H, 13C
1H
None
232 ꢀC
192 ꢀC
—
185 ꢀC
181–182 ꢀC
Not reported
185.7 ꢀC (DSC)
—
—
>99
>99
1H
None
1H, 13C, 15N
167.9 ꢀC (DSC)
62:38e
a
In benzene.
In ethanol.
b
c
d
e
The authors do not assign the structure but from the melting point and the 1H and 13C NMR data they report that the compound is undoubtedly the 2-isomer 4.
For 12 h with K3PO4.
In DMF.
of the other isomer were lost in the purification), we decided
to repeat the synthesis (Table 1, entry 10) and to carry out
a complete NMR study as well as to examine the relative sta-
bilities of compounds 3 and 4.
2.2. NMR characterization
Although there are some previous reports on the NMR spec-
tra of 1-(20,40-dinitrophenyl)-1H-benzotriazole (3) and 2-
(20,40-dinitrophenyl)-2H-benzotriazole (4) (see Table 1),
1
we have recorded the H (Table 2), 13C (Table 3), and 15N
2. Results and discussion
NMR spectra (Table 4) in DMSO-d6 solution and for the
two last nuclei also in the solid state (CPMAS).
2.1. Synthesis and DSC melting points
A NOESYexperiment in DMSO-d6 solution of compound 3
shows a correlation between H60 and H7 (Fig. 1), which is
consistent with a Z conformation in such polar solvent, con-
trary to the theoretical predictions in the gas phase (see Sec-
tion 2.3).
We have used the Wilshire’s procedure to obtain both iso-
mers of N-(20,40-dinitrophenyl)benzotriazole, the 1(3)- and
the 2-substituted, using DMF as solvent.1 The melting points
were determined by DSC as being very close to those re-
ported by all authors save those of Beletskaya et al.,8 which
should be considered erroneous. We have also noted, during
the DSC experiments, the absence of any phase transition.
The assignments were based on the usual 2D methodologies
and are consistent with literature results on benzotriazoles
Table 2. 1H NMR (d in ppm and J in Hz) of 3 and 4 in DMSO-d6
Compound
H-4
H-5
H-6
H-7
Others
3
3
4
0
3
8.27 (ddd), JH5¼8.6,
7.60 (ddd), JH6¼7.7,
7.75 (ddd),
7.85 (ddd)
9.07 (d, 1H, H-30, JH-5 ¼2.5);
8.39 (d, 1H, H-60)
4JH6¼5JH7¼0.9
4JH7¼0.9
3JH7¼8.3
8.80 (dd, 1H, H-50, JH-6 ¼8.8);
3
0
3
3
4
9.02 (d, 1H, H-30, JH-5 ¼2.5);
0
4
8.04 (m), JH5¼8.8,
7.58 (m), JH6¼6.6,
7.58 (m)
8.04 (m)
3
5JH7¼0.8
4JH7¼0.9
8.72 (dd, 1H, H-50, JH-6 ¼8.9);
0
8.51 (d, 1H, H-60)
Table 3. 13C NMR (d in ppm and J in Hz) of 3 and 4 in DMSO-d6 and in the solid state
Compound
C-4
C-5
C-6
C-7
C-3a
C-7a
3 (DMSO-d6) 120.1, 1J¼166.9,
125.6, 1J¼163.9,
129.8, 1J¼164.3,
110.3, 1J¼170.0,
145.3, 2J¼10.0,
132.4, 3J¼10.6,
3J¼7.6
3J¼7.5
3J¼7.9
3J¼8.3
3J¼4.9
3J¼6.5
3 (CPMAS)a 119
127
130
129.2
111
118.4
146
134
145.2
4 (DMSO-d6) 118.4, 1J¼168.1
129.2, 1J¼163.2,
3J¼8.2, 2J¼1.6
122.9b
145.2, 3J¼9.4,
3J¼5.4
4 (CPMAS) 121.4b
Other signals
124.6b
115.1b
145.4b
140.7b
3 (DMSO-d6) 147.4 (C-40, 3J¼10.6, J¼5.1); 144.1 (C-20, 3J¼8.2, J¼4.9); 132.6 (C-10, 3J¼9.8, J¼6.9); 129.2 (C-50); 128.9 (C-60, 1J¼174.5);
2
2
3
121.8 (C-30, 1J¼177.2, 3J¼5.1)
3 (CPMAS)a 146 (C-40); 146 (C-20); 134 (C-10); 130 (C-50, C-60); 124 (C-30)
4 (DMSO-d6) 147.3 (C-40, 3J¼10.6, 2J¼4.9, J¼3.3); 143.0 (C-20, 3J¼7.9, 2J¼4.3, J¼1.6); 135.0 (C-10, 3J¼9.8, 3J¼6.9, 2J¼2.0);
2
4
1
1
128.3 (C-50, J¼176.2); 127.5 (C-60, J¼176.3); 121.2 (C-30, 1J¼177.1, 3J¼5.7, 4J¼1.6)
4 (CPMAS) 146.2 (C-40); 144.2 (C-20); 131.5 (C-10); 130.2 (C-50); 129.1 (C-60); 122.9 (C-30)
a
Very broad signals, between 1.1 and 1.8 ppm of width.
The assignment of these signals can be exchanged.
b

M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
Table 4. 15N NMR (d in ppm) of compounds 3 and 4 in DMSO-d6 and in the solid state
3739
Compound
N-1
N-2
N-3
Other
3 (DMSO-d6)
3 (CPMAS)
4 (DMSO-d6)
4 (CPMAS)
ꢁ156.9
n.o.
ꢁ4.1
ꢁ29.7
n.o.
ꢁ15.1 (NO2-20)
n.o.
ꢁ15.8 (NO2-40)
n.o.
n.o.
ꢁ123.0
ꢁ122.8
ꢁ62.8
ꢁ62.8
ꢁ14.5 (NO2-20)
ꢁ16.1 (NO2-40)
ꢁ71.9
n.o.
ꢁ12.4 (NO2-20)
ꢁ15.8 (NO2-40)
H6’
In the case of compound 4 in the solid state, only the signal
of N-3 was not observed. To estimate its position, GIAO/
B3LYP/6-31G* calculations were carried out on this com-
pound. Since there is a very good correlation between exper-
imental chemical shifts and calculated absolute shieldings,
the missing nitrogen signal should appear at about
ꢁ60 ppm (Table 5).
H3’
H5’
H7
H6 H5
H4
(ppm)
7.6
H6’
H7
8.0
2.3. Theoretical calculations
8.4
We have carried out density functional theory calculations
(B3LYP/6-31G**) on compounds 3 and 4 to know their rel-
ative stabilities. The results are reported in Table 6.
8.8
The most stable conformation of 3 in the gas phase has the
nitro group pointed toward the benzene ring, 3E. Probably
there is a C7eH/O]N hydrogen bond (calculated H/O
9.2
9.2
8.8
8.4
8.0
7.6
(ppm)
Figure 1. NOESY spectrum of compound 3 in DMSO-d6.
˚
distance is 2.86 A). Isomer 4 has a N3/NO2 distance of
˚
2.90 A (see Fig. 1) and a calculated geometry, which is
˚
rather similar to that of XEWLOAwith a distance of 2.65 A.
and other related azole derivatives.1,7,13–16 It should be noted
that in solution both isomers are easily identified on simple
symmetry considerations. For instance, the benzotriazole
moiety in the 1H NMR of isomer 3 appears as an ABCD sys-
tem while in isomer 4 the system is an AA0BB0 (see Table 2).
This is due to the free rotation (or, at least, liberation) about
the NeC inter-ring bond. This freedom disappears in the
solid state (Table 3). Since the broadening of the 13C signals
of compound 3 is unspecific, it is probably due to the planar
structure of the compound.17,18 Note for compound 4 in the
solid state the splitting of the signals of the benzotriazole
ring. Its structure is presumably planar with a stabilizing
orthogonal interaction19–21 between the N-atom of the nitro
group and the N-3 atom (Fig. 2). This makes all the atoms of
the 2H-benzotriazole ring different, but it cannot be
excluded, as an alternative explanation, the presence of
two independent molecules in the unit cell.
An important consequence drawn from the analysis of Table
6 values is that, although 3E is more stable than 3Z and 4, the
differences are small. Since the dipole moments of 3Z and 4
are larger than that of 3E, it is expected that an extra stabili-
zation would occur in polar solvents.
2.4. Isomerization processes
First, we will report the most significant experiments carried
out with compounds 3 and 4 in solution using H NMR at
1
400 MHz to monitor the isomerizations. The spectra re-
ported in Figure 3 correspond to the evolution of 4 in
DMF-d7 at 323 K.
(1) Isomer 3 is indefinitely stable (experimentally 43 days)
in DMSO-d6 solution at 295 K in what concerns isomer-
ization.
The 15N NMR results (Table 4) are less useful because in
several cases some signals could not be detected. This is par-
ticularly true for isomer 3 where no signal was observed in
the CPMAS spectrum.
(2) Isomer 4 is indefinitely stable in chloroform solution.
Table 5. 15N NMR, absolute shieldings (s, in ppm) and experimental chemi-
cal shifts (d in ppm) of compound 4
Atom
s
d
Experimental
Fitteda
N-1
N-2
N-3
NO2-20
NO2-40
MeNO2
ꢁ53.875
ꢁ71.91
ꢁ122.77
—
ꢁ12.39
ꢁ15.88
00.00
ꢁ70.5
ꢁ123.7
ꢁ60.7
ꢁ10.0
ꢁ15.6
ꢁ3.483
ꢁ63.199
ꢁ111.348
ꢁ105.9296
ꢁ117.75
b
Predicted value is given in italics.
[d(15N)¼ꢁ(127.4ꢂ2.3)ꢁ(1.06ꢂ0.03)s(15N), n¼5, r2¼0.998].
a
Figure 2. View of compound 4 showing the asymmetry generated by the
ortho-nitro group.
b
From Ref. 22.

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M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
Table 6. B3LYP/6-31G** energies (hartree), relative energies (kJ molꢁ1), and other properties of compounds 3, 4, and XEWLOA
O2N
O2N
N
N
N
N
N
N
NO2
4
XEWLOA
Compound
3Z
3E
4
XEWLOAa
Energy
E+ZPE
ꢁ1035.91225
ꢁ1035.72124
2.79
6.48
48.9
ꢁ1035.913498
ꢁ1035.72230
0.00
3.69
142.4
ꢁ1035.91351
ꢁ1035.72185
1.18
5.35
148.5
—
—
—
—
150.5
61.7
2.65
Erel (ZPE)
m (Debye)
N2(1)eN1(2)eC10eC20 (ꢀ)
OeNeC20eC10 (ꢀ)
35.9
3.02
34.5
4.20
42.6
2.90
˚
N2 (or N3)/NO2 (A)
From CSD.23
a
4
4
42 h, 15 min. at 323 K
(69.1% 4, 30.9% 3)
4
4
4
3
3
3
3
3
3
3
18 h at 323 K
(79.7% 4, 20.3% 3)
Recently dissolved 4
9.2 9.1 9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6
Figure 3. 1H NMR spectra showing the isomerization in DMF-d7 at 323 K of 2-isomer 4 into 1-isomer 3.
(3) Isomer 4 in DMSO-d6 solution slowly evolves to attain
asymptotically a mixture of 3+4 in a ratio that slightly
depends on the temperature, about 20% of 3 at 295 K
and about 15% of 3 at 323 K. The rates of these two ex-
periments are practically the same.
(4) Isomer 4 in DMF-d7 solution slowly (but faster than in
DMSO-d6) evolves to attain asymptotically a 50:50 mix-
ture of 3+4.
equilibrium and a0 is the initial concentration, in our case
of 4.24 Due to the fact that either the reaction is not an oppos-
ing reaction or that the forward and reverse reactions are not
of the first order, in all our cases there is an intercept a1 that
cannot be assumed to be 0 because it is highly significant,
ln[xe/(xeꢁx)]¼a1+(a0k/xe)tsec. We have explored other
models and one of the best, which takes account of the cur-
pffiffiffiffiffiffi
vature, is the use of tsec
.
The analysis of the kinetic data (see Supplementary data for
Tables of data) is rather complex since there is no standard
integrated equation that goes through all the points (see Sec-
tion 4). We have assumed that the reaction proceeds to a state
of equilibrium, which differs appreciably from completion.
For the case when the forward and reverse reactions are of
the first order, the integrated equation has the form ln[xe/
(xeꢁx)]¼(a0k/xe)tsec, where xe is the concentration at the
Applying the Eyring equation, we have obtained the follow-
ing results (Eqs. 1–3):
DMSO-d6; 295 K: a1 ¼ ð1:22 ꢂ 0:11Þ;
slope: ð3:63 ꢂ 0:25Þ ꢃ 10ꢁ7
;
k ¼ ð7:56 ꢂ 0:52Þ ꢃ 10ꢁ8 sꢁ1
;
DGz295 ¼ ð112:3 ꢂ 0:2Þ kJ molꢁ1
ð1Þ

M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
3741
In 1967, Kamel et al. reported that the reaction between 5
and 2b yielded a mixture of 6 (mp 185 ꢀC, minor, about
10%) and 7 (mp 222 ꢀC, major, about 90% in isolated prod-
ucts) without any amount of 8 (mp 170 ꢀC, synthesized by an
independent way).3 This result, based only on chemical
proofs, seemed doubtful to us because N-substitution reac-
tion of 5 yields mainly 5-nitro derivatives.25 Thus, either
Kamel’s assignment was wrong or the proportions were
not correct. We repeated the reaction as described and found
DMSO-d6; 323 K: a1 ¼ ð1:14 ꢂ 0:07Þ;
slope: ð5:16 ꢂ 0:25Þ ꢃ 10ꢁ7
;
k ¼ ð8:17 ꢂ 0:40Þ ꢃ 10ꢁ8 sꢁ1
;
DGz323 ¼ ð123:0 ꢂ 0:1Þ kJ molꢁ1
ð2Þ
ð3Þ
DMF-d7; 323 K: a1 ¼ ð0:98 ꢂ 0:04Þ;
slope: ð13:34 ꢂ 0:003Þ ꢃ 10ꢁ7
;
1
in the crude mixture by H NMR that the proportions are
k ¼ ð66:70 ꢂ 0:05Þ ꢃ 10ꢁ8 sꢁ1
;
50% of 6, 30% of 7, and 20% of 8. The melting points of
6–8 determined by DSC are somehow different from those
described by Kamel et al.3
DGz323 ¼ ð117:4 ꢂ 0:01Þ kJ molꢁ1
In our isomerization experiments of 4 in the presence of
5(6)-nitro-1H-benzotriazole (5), the composition depends
on the stoichiometry, but always consists in a mixture of 1,
3–7 (without traces of 8). This already establishes that the
isomerization process is intermolecular. Considering only
the four dinitrophenyl derivatives (3, 4, 6, and 7) and the
We have carried out two other experiments of isomerization
of 4 in DMSO-d6 at 323 K, both in the presence of 5(6)-ni-
tro-1H-benzotriazole (5) using two different 4/5 ratios, 1:2
and 1:1. In both cases a complex mixture of six compounds
(1, 3–7) was obtained (Scheme 2) that was monitored by
NMR as a function of time (Fig. 4).
O2N
O2N
N
N
N
N
N
N
N
N
N
NO2
NO2
N
N
N
H
H
4
O2N
1
5
3
O2N
NO2
O2N
O2N
N
N
N
N
N
N
N
N
N
O2N
O2N
8
O2N
7
6
NO2
NO2
Scheme 2. Compounds expected in the reaction between 4 and 5.
5
5
5
3
1
6
1
6
6
6
6
4
7
4
4
4
7
6
7
4
7
3
3 7
3
3
3
3
9.2 9.1 9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4
(ppm)
Figure 4. 1H NMR spectrum showing the isomerization in DMSO-d6 at 323 K of 2-isomer 4 in the presence of 5(6)-nitro-1H-benzotriazole (5) in a 1:2 ratio.
Assignments (d in ppm): 9.20 (H4, ), 9.10 (H30, ), 9.09 (H30, ), 9.04 (H30, ), 9.00 (H30, 4), 8.88 (H4, 5), 8.87 (H50, ), 8.85 (H7, ), 8.84 (H50, ), 8.78 (H50,
6
7
6
3
7
7
6
), 8.72 (H50, 4), 8.53 (H7, ), 8.50 (H60, 4), 8.50 (H4, ), 8.44 (H60, ), 8.42 (H60, ), 8.37 (H60, ), 8.34 (H5, ), 8.24 (H6, 5), 8.24 (H4, ), 8.05 (H7, ), 8.03
3
6
7
7
6
3
(H7, 5), 8.03 (H4, H7, 4), 7.87 (H4, H7, ), 7.82 (H7, ), 7.73 (H6, ), 7.57 (H5, H6, 4), 7.40 (H5, H6, ).
7
3
6
1
3
3
1

3742
M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
of 3/4 for the experiments in toluene and xylene where
only 3 was isolated) can be analyzed as depending on the
polarity and the acidity of the solvent, Reichardt’s ENT
and Swain’s Aj:26
ꢀ
ꢁ
½3ꢄ=½4ꢄratio ¼ ð50 ꢂ 2Þ ꢁ ð244 ꢂ 18ÞETN þ 170 ꢂ 20 Aj;
n ¼ 8; r2 ¼ 0:989
ð5Þ
Eq. 5 shows that the polarity of the solvent increases the
amount of the 2-substituted isomer 4 while the acidity favors
the 1-substituted isomer 3. These conclusions are related to
the tautomerism of benzotriazole [the 1(3)H-tautomer is
much more stable than the 2H one]27 and to the acid–base
equilibrium between benzotriazole 1 and its conjugated
anion 1ꢁ. The problem is complicated by the fact that both
the 1H-tautomer and the anion can yield the two isomers.
Katritzky and Wu assumed that the solvent polarity breaks
down the hydrogen bonds of the 1H-benzotriazole dimer
that shields the 2-position, favoring the 2-substituted iso-
mer.6 The acidity could shift the equilibrium between 1 and
1ꢁ and thus avoiding the reactivity of the anion, which ac-
cording to entry 5 of Table 1, affords only 4. Entry 6 (PTC,
both isomers formed) corresponds to a reflux in toluene in
the presence of K2CO3 plus a quaternary ammonium salt
and thus is not a typical reaction of 1ꢁ.8 Entries 7–9 corre-
spond to the exclusive formation of 3 although some of them
uses DMF as solvent,9 PTC and MW,10 and ionic liquids.11
Figure 5. Evolution of the mixture of dinitrophenylbenzotriazoles. The Y
variables are the percentages of the four components 3, 4, 6 and 7.
case with a 1:2 ratio of 4 and 5, the following plot is obtained
(Fig. 5) corresponding to 60 days. All the data for both cases
are given in Supplementary data.
Compound 4 (blue squares) disappears almost completely
being not only transformed mainly into its isomer 3 (blue
circles) but also into the two nitrobenzotriazole derivatives
6 (red triangles) and 7 (orange triangles). The 6/7 ratio is
almost constant (2.28 in the 2:1 mixture and 2.23 in the
1:1 mixture) but the ratio [3]/[4] varies linearly with time
(Eq. 4):
The isomerization experiments, without and with nitro-
benzotriazole, correspond to the species and the relation-
ships between themselves are represented in Scheme 3.
In DMSO-d6 or DMF-d7 solutions, compound 4 dissociates,
even in a small amount, to benzotriazolate anion 1ꢁ and to
the dinitrophenyl cation 2+. In a less polar solvent, like
CDCl3, the dissociation does not occur and 4 is stable. In
the absence of 5, the cation 2+ reacts with 1ꢁ to afford 4 since
the 2-position of the anion is the most reactive. But, although
less reactive, the 1(3)-position also react to yield 3 and
slowly the quantity of 3 increases because 3 is not dissoci-
ated into 1ꢁ and 2+. This kinetic stability of 3 compared to
4 is not necessarily related to its greater thermodynamic
stability (Table 6). Note that the isomerization of 4/3 is
not complete and an equilibrium is reached that is solvent
dependent. However, in the presence of nitrobenzotriazole
5 almost all 4 disappears. Another important observation is
that at 323 K the reaction in DMF is eight times faster
than in DMSO and affords much more 3, a fact probably re-
lated to the ETN values of both solvents (0.386 and 0.444) and
the already noted observation that a decrease in polarity
increases the amount of 3 (Eq. 5).
½3ꢄ=½4ꢄ ¼ ð0:304 ꢂ 0:007Þtdays; n ¼ 7; r2 ¼ 0:997
ð4Þ
The fact that no 8 was formed in these studies (DMSO) while
in our hands, the reaction of 2 and 5 (EtOH/AcONa) affords
8 is probably related to the different solvents used or to the
arylating agent, 2 or 2+ (Scheme 3). The same reason could
account for the ratio of 6/7, in the first case is 1.67 (50:30)
while in the cross-experiments is 2.25.
O2N
+
O2N
+
N
N
N
N
N
N
N
N
N
N
N
N
1–
1
5–
H
H
5
6
4
1–
5–
NO2
7
3
NO2
2
In the presence of nitrobenzotriazole 5 there should be an
equilibrium with 1ꢁ that leads to 5ꢁ (Scheme 3). This last
one would react with 2+ to afford 6 (major) and 7 (minor).
This is in contradiction with Kamel et al.3 who reported
that the reaction of 2a with 5 (EtOH/AcOEt) affords mainly
7 (the ratio of isolated compounds 6/7 is 1:9). Most probably
their assignment, based on chemical proofs, is erroneous; for
instance, the reaction of 5 with picryl chloride (EtOH/
AcOEt) yields a mixture of both picryl isomers in a ratio
44% of 6-nitro and 56% of 5-nitro.28
+
Scheme 3. The isomerization experiments, all species solvated by DMSO-
d6. The red arrow with the red point corresponds to a not observed process.
The reaction of 1-halo-2,4-dinitrobenzenes 2 (there is no vis-
ible effect of the halogen) with benzotriazole 1 depends on
the nature, neutral 1 or anion 1ꢁ, of the azole as well as on
the solvent. With neutral benzotriazole, the solvent effects
summarized in Table 1 (we have assumed a 98:2 mixture

M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
3743
3. Conclusive remarks
resolution 0.42–0.63 Hz per point; WALTZ-16 was used
for broadband proton decoupling; the FIDS were multiplied
by an exponential weighting (lb¼1 Hz) before Fourier trans-
formation. 1D 15N NMR was acquired using inverse gated
decoupling and typical parameters were spectral width
14,368 Hz, pulse width 28.5 ms, relaxation delay 30 s, and
resolution 0.44 Hz per point; WALTZ-16 was used for proton
decoupling; the FIDS were multiplied by an exponential
weighting (lb¼2 Hz) before Fourier transformation. 2D
(1He1H) gs-COSY and inverse proton detected heteronu-
clear shift correlation spectra, (1He13C) gs-HMQC,
(1He13C) gs-HMBC, and (1He15N) gs-HMBC, were ac-
quired and processed using standard Bruker NMR software
and in non-phase-sensitive mode and the NOESYexperiment
was acquired with a mixing time of 1100 ms. Gradient selec-
tion was achieved through a 5% sine truncated shaped pulse
gradient of 1 ms.
All the previous reports compiled in Table 1, on the reaction
between 1H-benzotriazole (1) and 1-halo-2,4-dinitrobenz-
enes (2) represented in Scheme 1, have based their explana-
tion about the 3/4 ratios on kinetic effects. Nobody has
considered that 4 could be formed just to isomerize into 3.
For instance, Beletskaya et al.8 observed that longer reaction
times increase the proportion of 3. Isomerizations could
have occurred under microwave irradiation,10 or with the
use of ionic liquids as solvents,11 thus explaining the ob-
served regioselectivity.
The fact that N-substituted benzotriazoles (like most azoles)
can isomerize has been known for long time but they concern
substituents like N-(N0,N0-dialkylaminomethyl) that are easy
to cleave and be rapidly equilibrated: the equilibrium of
[1-isomer]/[2-isomer] is 5.5 in CDCl3 and >9 in DMSO.29
However, no example is known of isomerization of an aryl
group.
4.2.2. Solid state. 13C (100.73 MHz) and 15N (40.60 MHz)
CPMAS NMR spectra were obtained on a Bruker WB 400
spectrometer at 300 K using a 4 mm DVT probehead. Sam-
ples were carefully packed in a 4-mm diameter cylindrical
zirconia rotor with Kel-F end-caps. Operating conditions in-
volved 3.2 ms 90ꢀ 1H pulses and decoupling field strength of
78.1 kHz by TPPM sequence. 13C spectra were originally
referenced to a glycine sample and then the chemical shifts
were recalculated to Me4Si (for the carbonyl atom d (glyci-
ne)¼176.1 ppm) and 15N spectra to 15NH4Cl and then con-
verted to nitromethane scale using the relationship: d 15N
(nitromethane)¼d 15N(ammonium chloride)ꢁ338.1 ppm.
The typical acquisition parameters for 13C CPMAS were:
spectral width 40 kHz; recycle delay 5 s for 3 and 60 s for
4; acquisition time 30 ms; contact time 2 ms; and spin rate
12 kHz. And for 15N CPMAS were: spectral width
40 kHz; recycle delay 5 s for 3 and 60 s for 4; acquisition
time 35 ms; contact time 9 ms; and spin rate 6 kHz.
Minkin et al.29,30 reported that no N,N-migration of a 2,4,6-
trinitrophenyl (picryl) group was observed by H NMR in
solutions of 1-picryl-3,5-dimethylpyrazole in nitrobenzene
even at 445 K, that is, the energy barrier DGz445 is higher
than 100 kJ molꢁ1, confirming that dissociating solvents,
like DMSO or DMF, are necessary to cleave the NeC bond.
1
4. Experimental
4.1. Synthesis and DSC melting points
Compounds 3 and 4 were prepared according to Wilshire’s
experimental conditions and separated by column chromato-
graphy over silica gel using a mixture of chloroform/hexane
(99:1).1 The reaction of 1-chloro-2,4-dinitrobenzene and
5(6)-nitrobenzotriazole in the conditions reported by Kamel
et al. (1-chloro-2,4-dinitrobenzene in EtOH/AcONa at
reflux)3 affords a mixture of 1-(20,40-dinitrophenyl)-5-nitro-
1H-benzotriazole (6), mp 189.8 ꢀC, lit. mp 185 ꢀC,3
1-(20,40-dinitrophenyl)-6-nitro-1H-benzotriazole (7), several
melting and phase transitions around 220 ꢀC, lit. mp 222 ꢀC,3
and 2-(20,40-dinitrophenyl)-5-nitro-2H-benzotriazole (8), mp
195.9 ꢀC, lit. mp 170 ꢀC.3
4.3. Theoretical calculations
Energy calculations were carried out at the hybrid Becke
B3LYP/6-31G** level l31–33 with basis sets of Gaussian-
type functions34 within the Windows Titan 1.0.5 package and
include zero point energy (ZPE) corrections. Starting geom-
etriesfor the calculations were the optimized ones obtainedat
the HF/6-31G** level. In all cases the final geometries really
correspond to the minima as no imaginary frequencies ap-
pear. GIAO/B3LYP/6-31G* absolute shieldings calculations
were carried out with the Gaussian 03 package.35
Melting points were determined by DSC on a Seiko DSC
220C connected to a Model SSC5200H Disk Station. The
heating rates were 5ꢀ per minute with N2 as the purge gas.
4.4. Kinetic experiments
4.2. NMR measurements
4.4.1. Experiment 1. Compound 4 (40.2 mg), solvent
DMSO-d6 (0.75 mL, 0.1879 M), T¼295 K, from 58,140 s
to 168 days, 22 measures. Assuming that the final mixture
contains 79.18% of 4 (20.82% of 3), a0¼0.1879, equi-
librium¼0.7918, xe¼0.0391208, removing the first point
and the latter one that corresponds to the equilibrium:
4.2.1. Solution. The spectra were recorded on a Bruker DRX
1
400 (9.4 T, 400.13 MHz for H, 100.62 MHz for 13C, and
40.56 MHz for 15N) spectrometer with a 5-mm inverse-
detection HeX probe equipped with a z-gradient coil at
300 K. Chemical shifts (d in ppm) are given from internal sol-
1
vent, DMSO-d6 2.49 for H and 39.5 for 13C, and for 15N,
ꢂ
ꢃ
ꢀ
ꢁ
ꢀ
ꢁ
ln xe=xe ꢁ x ¼ 1:22 ꢂ 0:11 þ 3:63 ꢂ 0:25 ꢃ 10ꢁ7ts;
nitromethane (0.00) was used as external references. Typical
parameters for 1H NMR spectra were spectral width 3100–
3900 Hz, pulse width 7.5 ms, and resolution 0.19–0.24 Hz
per point. Typical parameters for 13C NMR spectra were
spectral width 13,800–20,600 Hz, pulse width 10.6 ms, and
ꢀ
ꢁ
n ¼ 20; r2 ¼ 0:922; k ¼ 7:56 ꢂ 0:52 ꢃ 10ꢁ8 sꢁ1 ð6Þ
4.4.2. Experiment 2. Compound 4 (40.2 mg), solvent
DMSO-d6 (0.75 mL, 0.1879 M), T¼323 K, from 18,000 s

3744
M. D. Santa Marꢀıa et al. / Tetrahedron 63 (2007) 3737–3744
15. Elguero, J.; Fruchier, A.; Tjiou, E. M.; Trofimenko, S. Chem.
Heterocycl. Comp. 1995, 1006.
to 109 days, 17 measures. Assuming that the final mixture
contains 84.17% of 4 (15.83% of 3), a0¼0.1879, equi-
librium¼0.8417, xe¼0.0297446, removing the first point
and the latter one that corresponds to the equilibrium:
ꢀ
ꢀ
16. Claramunt, R. M.; Sanz, D.; Lopez, C.; Jimenez, J. A.; Jimeno,
M. L.; Elguero, J.; Fruchier, A. Magn. Reson. Chem. 1997,
35, 75.
ꢂ
ꢃ
ꢀ
ꢁ
ꢀ
ꢁ
ln xe=xe ꢁ x ¼ 1:14 ꢂ 0:07 þ 5:16 ꢂ 0:25 ꢃ 10ꢁ7ts;
17. It is known that the closest to sphericity a molecule is, the eas-
iest it tumble and consequently the better is the resolution.18
18. Alemany, L. B.; Grant, D. M.; Pugmire, R. J.; Alger, T. D.;
Kurt, W.; Zilm, K. W. J. Am. Chem. Soc. 1983, 105, 2142.
ꢀ
ꢁ
n ¼ 15; r2 ¼ 0:971; k ¼ 8:17 ꢂ 0:40 ꢃ 10ꢁ8 sꢁ1 ð7Þ
4.4.3. Experiment 3. Compound 4 (40.2 mg), solvent DMF-
d7 (0.75 mL, 0.1879 M), T¼323 K, from 64,800 s to 45
days, 12 measures. Assuming that the final mixture contains
50.00% of 4 (50.00% of 3), a0¼0.1879, equilibrium¼
0.5000, xe¼0.093950, removing the first point and the latter
one that corresponds to the equilibrium:
ꢀ
19. Yap, G. P. A.; Jove, F. A.; Claramunt, R. M.; Sanz, D.; Alkorta,
I.; Elguero, J. Aust. J. Chem. 2005, 58, 817.
€
20. Paulini, R.; Muller, K.; Diederich, F. Angew. Chem., Int. Ed.
2005, 44, 1788.
21. Pinilla, E.; Torres, M. R.; Claramunt, R. M.; Sanz, D.; Prakash,
R.; Singh, S. P.; Alkorta, I.; Elguero, J. ARKIVOC 2006, ii, 135.
22. Alkorta, I.; Elguero, J. Struct. Chem. 1988, 9, 187.
23. CSD version 5.27 (updated January, May and August 2006):
Allen, F. H. Acta Crystallogr., Sect. B 2002, 58, 380.
24. Laidler, K. J. Chemical Kinetics; McGraw-Hill: New York, NY,
1965; pp 19–21.
ꢂ
ꢃ
ꢀ
ꢁ
ꢀ
ꢁ
ln xe=xe ꢁ x ¼ 0:98 ꢂ 0:04 þ 13:34 ꢂ 0:003 ꢃ 10ꢁ7ts;
ꢀ
ꢁ
n ¼ 10; r2 ¼ 0:996; k ¼ 66:70 ꢂ 0:05 ꢃ 10ꢁ8 sꢁ1 ð8Þ
25. Schellhammer, C. W.; Schroeder, J.; Joop, N. Tetrahedron1970,
26, 497; Elguero, J.; Fruchier, A.; Pappalardo, L.; Pardo, M. C.
An. Quim. 1978, 74, 1529; Wiench, J. W.; Koprowski, M.;
Stefaniak, L.; Webb, G. A. Pol. J. Chem. 2002, 76, 525.
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Chemistry, 3rd ed.; Wiley-VCH: Weinheim, 2003.
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Acknowledgements
Thanks are given to MCyT of Spain for financial support,
project numbers BQU2003-00976, BQU2003-01251, and
CTQ2006-02586. We are greatly indebted to Dr. Ibon
Alkorta (IQM, CSIC) for the calculation of the 15N absolute
shieldings of compound 4.
28. Coburn, M. D. J. Heterocycl. Chem. 1973, 10, 743.
29. Minkin, V. I.; Garnowski, A. D.; Elguero, J.; Katritzky, A. R.;
Denisko, O. V. Adv. Heterocycl. Chem. 2000, 76, 157 (see page
195).
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.02.083.
30. Minkin, V. I.; Olekhnovich, L. P.; ZhdanovYu, A.; Mikhailov,
I. E.; Metlushenko, V. P.; Ivanchenko, N. M. J. Org. Chem.
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