Flash vacuum pyrolysis of azolylacroleins and azolylbutadienes

Article abstract of DOI:10.1016/j.tet.2011.11.034

2-Aryl-5-acroleinyl-1,2,3,4-tetrazoles (1a-d) and 2-aryl-5-butadienyl-1,2, 3,4-tetrazoles (1e-g) were subjected to flash vacuum pyrolysis. Acroleinyl derivatives resulted in nitrogen extrusion to give nitrilimines followed by ring closure to give the corresponding indazoles 3a-d in good yields. On the other hand, butadiene derivatives underwent ring fragmentation to give p-substituted anilines without formation of the expected indazoles. Differences between thermal behaviour of 2-(4-chlorophenyl)-5-acroleinyl-1,2,3,4-tetrazole (1c) and 1-(4-chlorophenyl)-4-acroleinyl-1,2,3-triazole (2) were studied in details. DFT calculations have been used to examine the nitrilimine and carbene nature of the intermediates involved in the thermal reactions of azolyl derivatives.

Full text of DOI:10.1016/j.tet.2011.11.034

Tetrahedron 68 (2012) 1299e1305
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Flash vacuum pyrolysis of azolylacroleins and azolylbutadienes
a
b
c
c
,
a
*
ꢀ
€
ꢀ
Paola L. Lucero , Walter J. Pelaez , Zsuzsanna Riedl , Gyorgy Hajos , Elizabeth L. Moyano ,
Gloria I. Yranzo a
,
1
a
ꢀ
ꢀ
ꢀ
INFIQCdDepartamento de Química Organica, Facultad de Ciencias Químicas, Universidad Nacional de Cordoba, Cordoba, Argentina
INFIQCdDepartamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Cordoba, Cordoba, Argentina
Chemical Research Center, Institute of Biomolecular Chemistry, Pusztaszeri ut 59, H-1025 Budapest, Hungary
b
c
ꢀ
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2011
Received in revised form 26 October 2011
Accepted 14 November 2011
Available online 26 November 2011
2-Aryl-5-acroleinyl-1,2,3,4-tetrazoles (1aed) and 2-aryl-5-butadienyl-1,2,3,4-tetrazoles (1eeg) were
subjected to flash vacuum pyrolysis. Acroleinyl derivatives resulted in nitrogen extrusion to give ni-
trilimines followed by ring closure to give the corresponding indazoles 3aed in good yields. On the other
hand, butadiene derivatives underwent ring fragmentation to give p-substituted anilines without for-
mation of the expected indazoles. Differences between thermal behaviour of 2-(4-chlorophenyl)-5-
acroleinyl-1,2,3,4-tetrazole (1c) and 1-(4-chlorophenyl)-4-acroleinyl-1,2,3-triazole (2) were studied in
details. DFT calculations have been used to examine the nitrilimine and carbene nature of the in-
termediates involved in the thermal reactions of azolyl derivatives.
Keywords:
Pyrolysis
Tetrazole
Nitrilimine
Indazole
Ó 2011 Elsevier Ltd. All rights reserved.
Nitrogen extrusion
1. Introduction
In particular, thermolysis of 1,5-disubstituted tetrazoles differs
from that of the 2,5-disubstituted derivatives because nitrogen
Flash vacuum pyrolysis (FVP) consists of subjecting a molecule
to high temperature over a short period of time (w10ꢀ2 s). This
process allows the acquisition of kinetic as well as unstable prod-
ucts and may be suitable for synthetic purposes or for the study of
reaction mechanisms. FVP is used both as a single-step synthetic
procedure and as a complement to a multistep synthesis. These
reactions are generally clean and without solvent, so allow explo-
ration of reactive species, such as carbenes, radicals, nitrenes and
concerted reactions. Thus, FVP is an excellent technique for the
study of intramolecular reactions, such as elimination, cyclization
and generation of products that cannot be prepared in solution in
thermal reactions. Several reviews concerning FVP have been re-
ported1 and a worldwide book concerning synthetic gas-phase
transformations has also been published.2 Many nitrogen hetero-
cyclic compounds including pyrazoles, isoxazoles, triazines, tri-
azoles and tetrazoles have been studied under thermal gas-phase
conditions as an appropriate way to obtain new heterocycles.3
In the course of our pyrolytic studies we have focused on rings
containing NeN double bonds, due to their ability to eliminate ni-
trogen, generating reactive species, which could undergo rear-
rangement togive monocyclic and fused N-heterocyclic compounds.
elimination in the former case produces nitrenes and carbodii-
mides that rearrange to pyrazoles,4 thiadiazoles,5 oxadiazoles6 and
triazoles7 while in the latter gives nitrilamines.8
In this work, FVP methodology has been applied to prepare new
acroleinylindazoles (3aed) in good yields starting from 2-aryl-5-
acroleinyltetrazole precursors 1aed. In contrast to this result, 2-
aryl-5-butadienyltetrazoles 1eeg afforded p-substituted anilines
rather than indazoles. In addition, FVP reactions of 1-(4-
chlorophenyl)-4-acroleinyl-1,2,3-triazole 2 were performed in or-
der to assess the reactivity of tetrazole and triazole rings under
similar thermal conditions (Fig. 1). Theoretical calculations con-
cerning the assumed nitrilimine and carbene intermediates were
also performed to understand the mechanism operating in the ni-
trogen elimination of azolyl derivatives 1 and 2.
2. Results and discussion
Acroleinyltetrazoles (1aed) and butadienyltetrazoles (1eeg)
were prepared from 3-aryltetrazolo[1,5-a]pyridinium salts,
whereas 1-(4-chlorophenyl)-4-acroleinyl-1,2,3-triazole (2) was
prepared from 1,3-diaryl[1,2,3]triazolo[1,5-a]pyridinium salts
according to a literature procedure.9 In all cases the trans isomers of
1 and 2 were used in the thermal reactions. FVP reactions of these
azolyl derivatives were performed in a Vycor glass reactor with
ꢀ
* Corresponding author. E-mail address: ghajos@chemres.hu (G. Hajos).
1
Deceased.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.034

1300
P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
R2
N N
N N
N N
O
O
X
N
N
N
N
N
R1
R1
Cl
1a R1 = CH(CH3)2
1b R1 = OCH3
1c R1 = Cl
1e X = CH2, R1 = Br, R2 = CH3
2
1f X = CH2, R1 = CO2Et, R2 = H
1g X = CHCH3, R1 = CO2Et, R2 = H
1d R1 = F
Fig. 1. Azolyl derivatives studied under FVP conditions.
pressures of w10ꢀ2 Torr and contact times of w10ꢀ2 s. In the case of
substrate 1g all efforts to achieve volatilization of the sample failed,
and the low vapour pressure of this compound promoted de-
composition in the sample probe without passage through the hot
tube.
Gas-phase reactions of acroleinyltetrazoles (1aed) were carried
out between 250 and 370 ꢁC (Scheme 1). These reactions were
clean and 3-acroleinylindazoles (3aed) were obtained in high
yields (60e98%). The results are summarized in Table 1. In all cases,
when a 100% conversion of the starting tetrazole was achieved,
small amounts of two by-products: formylindenes 4 and indenes 5
were also detected (Scheme 2).
isomerizes to the more stable aromatic tautomers 1H-indazoles
3aed.
This intermediate (i) is, however, a flexible molecule, which can
adopt its geometry depending on the reaction conditions.8a,10 The
generation of nitrilimines from 2,5-disubstituted tetrazoles has
been previously studied in thermal8a,10 and photochemical re-
actions.11 Thermal studies in the gas and solution phase have
shown that 2,5-disubstituted tetrazoles are usually less stable than
1,5-disubstituted ones,12 and that the intermediate nitrilimine re-
acts according to the temperature, solvent and nature of the sub-
stituent in position 2 of the initial tetrazole. Thus, electron-
withdrawing substituents decrease the energy barrier of the
Scheme 1. Formation of 3-acroleinylindazole (3) by FVP starting from tetrazolylacrolein (1).
transformation of tetrazole into the nitrilimine intermediate. We
also observed that the fluoroaryl derivative 1d was completely
transformed into 3d at a reaction temperature lower than that used
with the other substrates.
Table 1
FVP reactions of tetrazoles 1aed
Compound
R1
T (ꢁC)
% 1
% 3a
% 4þ5
d
1a
CH(CH3)2
350
370
250
280
300
250
300
250
280
38
d
55
5
d
39
1
62
92
28
60
37
61
95
73
98
When the temperature is high enough, 3H-indazole (ii), i.e., the
precursor of 3, eliminates nitrogen to give 1H-indene-carbaldehyde
4 via carbene intermediates iii (Scheme 2). In general, loss of this
second nitrogen molecule in indazoles requires high temperature
(800 ꢁC) as reported in case of pyrolysis of 3-phenyl-indazole to give
fluorene.10a In our experiments, these reactions occurred at low
temperatures (about 300 ꢁC); therefore, thermal instability of
indazoles 3aed could be ascribed to the electronic effect of an
acroleinyl substituent. This behaviour resembles the transformation
observed with nitrogen extrusion of 3-(2-furyl)-indazole, where
benzofulvene derivatives were obtained at 400 ꢁC.10b
8
1b
OCH3
17 (1:6)b
35 (1:8)
63 (1:12)
d
1c
Cl
F
4
d
2
1d
27
d
a
Values determined by 1H NMR spectroscopy.
Total amount and relative ratio of indenes 4 and 5 determined by GC/MS.
b
The formation of indazoles 3aed could be rationalized by a ni-
trogen extrusion reaction in the starting tetrazole ring (Scheme 1).
The intermediate proposed for these transformations is repre-
sented by the nitrilimine resonance structure (i), which initially
undergoes a [1,5] dipolar cyclization with participation of one
double bond of the phenyl ring to give 4H-indazoles (ii), which
In all cases, compounds 4aed were detected as a mixtures of 5-
substituted-1H-indene-1-carbaldehyde (1H-5R1) and 6-substituted-
1H-indene-3-carbaldehyde (1H-6R1), which were in equilibrium.
Thermal isomerization of indenes is a well-known thermal reaction
and the amount of each isomer depends on the reaction conditions.13

P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
1301
O
O
R1
R1
N2
H
R1
N
O
O
N
4a-d
4a-d
ii
1H-5R1
1H-6R1
R1
- CO
O
iii
fvp
R1
R1
R1
N
N
H
5a-d
5a-d
3a-d
1H-5R1
1H-6R1
Scheme 2. Formation of indenes under FVP conditions.
Carbaldehydes 4 afforded decarbonylation to give indenes 5 under
FVP conditions. A gas chromatography analysis of the mixture of
indenes in the FVP of 1b indicated that the ratio of 4b/5b decreased as
the temperature increased, the loss of CO being a favoured process
under all thermal conditions (Table 1). In case of methoxy derivative
1b formation of indenes became important giving a 63% yield of these
products and only 37% of 3b at 300 ꢁC. This feature could be explained
by theabilityof the methoxygrouptostabilizethecarbeneiiiinvolved
in the N2 elimination reaction. Thus, the order of reactivity of 3aed is
in concordance with the ability of the substituents to stabilize the
positive charge density by resonance effect: OCH3>ClwF>CH(CH3)2.
Gas-phase pyrolysis of butadienetetrazoles 1eef proceeded in
a different fashion compared to that of acroleinyl derivatives 1aed.
Thus, reactions performed at 200e400 ꢁC afforded p-substituted
anilines 6eef (<20% yield) as the main products without formation
of the expected butadienylindazoles (Scheme 3). In the reaction
mixture some volatile compounds including butadiene and un-
saturated nitriles were also detected and their relative amount
gradually increased with temperature. Fragmentation of nitrili-
mines iv could be attributed to a less stabilizing effect of the alkenyl
substituent compared to the acroleinyl moiety also supported by
results of calculations discussed below.
Formation of anilines 6eef could be rationalized by de-
composition of the nitrilimines iv initially generated. Two possi-
bilities can be proposed: either iv affords a conjugated nitrile and
nitrene (v) by NeN bond fragmentation (pathway a in Scheme 3) or
a CeC cleavage occurs to give a nitrilimine (vi), which also yields
nitrene (v) by hydrogen cyanide elimination (pathway b). In both
cases hydrogen abstraction by v may result in formation of anilines
6eef. It is known that nitrene species abstract hydrogen atoms to
generate amines when a hydrogen radical source is available.13 In
our reactions, when toluene vapour was used as carrier gas
bibenzyl was formed being an indicative of the presence of radicals
in the reaction mixture.
Acroleinyltriazole 2, a deaza-analogue of 1c, was also subjected
to investigation under FVP conditions. The first predictable obser-
vation was that a high furnace temperature (300e400 ꢁC) was re-
quired for the transformation of 2. Analysis of the pyrolysate at
400 ꢁC indicated a mixture of isomeric indoles 7 and 8 (46%) and N-
(furanylmethylene)aniline 9 (48%) as main products (Scheme 4).
The thermal formation of indoles from 1,4-disubstituted-1,2,3-
triazoles is a very well-known procedure.14 However, there is no
precedent for the thermal study of triazole containing acroleinyl
substituents in the ring.
CH
N
N
+
R2
b
R2
N
R1
vi
R2
N
fvp
N2
HCN
N
N
N
N
a
N
NH2
R2
+
R1
R1
iv
1e R1 = Br, R2 = CH3
1f R1 = CO2Et, R2 = H
R1
R1
6e-f
N
v
Scheme 3. FVP reactions of 2-aryl-5-butadienyl-1,2,3,4-tetrazoles 1e,f.

1302
P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
Scheme 4. FVP of 1-(4-chlorophenyl)-4-acroleinyl-1,2,3-triazole 2.
The analysis of the mixture of 2- and 3-acroleinylindoles in the
closure reaction of ix to form the furan derivative requires higher
energy than the other rearrangements. In addition, interconversion
of carbene ix (Z) to carbene ix (E) is necessary to achieve the orien-
tation that allows overlapping between the oxygen lone pair of the
carbonyl group and the empty p-orbital of the carbene (Scheme 5).
pyrolysate showed a preponderance of 3-substituted isomer 7 at all
temperatures. As a result of the nitrogen elimination, obviously
iminocarbene vii is formed first, and insertion of the carbene into
the aromatic CeH bond can yield directly indole 7 (pathway a in
Scheme 4). The formation of 8 through pathway b would require
the intermediacy of 1H-azirine viii in the interconversion of imi-
nocarbenes vii and ix. It was reported that the formation of the
indole mixture could be ascribed to the intermediacy of 1H-azir-
ines.14b Looking at the reactivity of azirine, a preponderance of 3-
substituted indole 7 suggests that cyclization of vii to 7 (i.e.,
pathway a in Scheme 4) may be faster than formation of ix followed
by cyclization to 8 (pathway b in Scheme 4). On the other hand, the
thermal isomerization of 3-indole to 2-indole by a sigmatropic
[1,5]-shift of a migratory group is well known.14c Although there is
no information about the efficiency of acroleinyl moiety as a mi-
grating group under thermal conditions, it cannot be discarded.
Thus, formation of indole 8 could be rationalized in terms of the
rearrangement of carbene ix and/or the rearrangement of indole 7.
In addition, a very interesting finding was the presence of
furanylmethylene-aniline (9) in the reaction mixture. This could be
explained by the intermediacy of the iminocarbene ix. Thus, this
initial intermediate could undergo a [1,5] dipolar cyclization in
which the carbene carbon atom attaches to the carbonyl oxygen
atom to form the five-membered furan ring (pathway c in Scheme
4). Similar rearrangements were observed in the pyrolysis of dif-
ferent triazoles to give oxazoles.15 Experimental observations
showed that furanyl derivative 9 could be detected by a careful GC/
MS analysis, but it immediately underwent hydrolysis to 2-
furaldehyde and 4-chloroaniline. In order to confirm the structure
of 9, p-chloroaniline was separately synthesized25 from furfural and
p-chloroaniline. Physical data of the synthesized 9 proved to be
entirely identical to those of the product obtained in the FVP
reactions.
Scheme 5. Isomerization of carbene ix (Z) to carbene ix (E) under FVP conditions.
ZeE Isomerization of azolylalkenyl derivatives under FVP con-
ditions has been described in the literature.17 Although equilibrium
between the Z- and E-alkenylindazoles could take place under gas-
phase thermal conditions, we consider it would be minimal at the
low temperature used herein. The alkenylindazole obtained in the
pyrolysate was therefore the stable Z-configuration isomer. Pre-
vious calculations have also indicated that a minimal energy barrier
is associated with this type of interconversion in iminocarbenes.18
The structures of the intermediates involved in the FVP re-
actions of 1 and 2 were calculated with the Gaussian03 program
system,19 using a DFT method with B3LYP/6-311þþG (2df,pd) un-
restricted valence basis set with polarization and diffuse function
for all atoms. All geometries were optimized and characterized by
vibrational analysis. Shielding values were calculated for the opti-
mized geometries using the gauge including atomic orbitals
method (GIAO).20 Combination of the density-functional theory
(DFT) and the GIAO method was used as an advantageous pro-
cedure for measuring chemical shielding properties.21
Addition to the carbonyl oxygen atom (Scheme 4, route c), in-
sertion into the aromatic CeH bond (route a), and insertion in the
N]C double bond to give azirine viii are competitive reactions of
iminocarbene ix. Such reactions are well known in gas-phase car-
bene chemistry.16 The finding that pyrolysis of 2 at 350 ꢁC afforded
only indoles 7 and 8, while 9 was absent suggests that the ring
In order to understand the mechanism operating in our thermal
reactions, the electronic structure of the nitrilimines (i.e., i in
Scheme 1 and iv in Scheme 3, for the four possible representations
see Fig. 3) involved in these transformations was calculated
according to Mawhinney’s previous theoretical studies.22b Thus,

P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
1303
three structures were considered: planar Cs and non-planar C1
structures, and the cyclic species C (Fig. 2). Cs and C1 electronic
structures were therefore necessary to determine the effects of
substitution on the flexibility of nitrilimine as described in the lit-
erature.23 Based on the geometry of the YCN fragment, the Cs ar-
rangement can be described as a combination of propargylic (Fig. 3,
a) and allylic (c), while the C1 structure posses the allenic (b) and
carbenic form (d) as major contributors. Considering the CNN
fragment, (a) and (b) structures can be described as linear units,
while (c) and (d) are bent. However, it was determined that the
angle values YCN and CNN are required for a proper description of
the nitrilimine geometry involving all structures (aed).22b
showing a behaviour similar to that of borane derivative 11 de-
scribed in the literature.22a These findings indicate that there was
a poor contribution of carbenic species. We also found that the
values of NNX angles were similar for all evaluated intermediates,
independently of the N-aryl substitution. Table 2 shows that all
intermediates from 1aed, Cs and C1 structures corresponded to two
stationary points that are almost isoenergetic, the energy differ-
ence between them being of only about 6 kcal between them. In-
termediates 10, 12e14, on the other hand, were described as
structures with more carbene character and, in these cases; Cs
corresponded to a transition state (TS). The increase in the carbene
character could be associated with a decrease in the YCN and CNN
Fig. 2. Intermediates in the FVP reactions of acroleinyltetrazoles.
bond angles. The values of these angles described for 12 and 13 are
typical of singlet carbenes.22a
O
O
N
O
O
N
On the other hand, the carbon absolute chemical shielding (siso
values) provides information on the nature of the carbenic struc-
tures.22b Carbenes generally present negative absolute chemical
shielding values, such as the diamine derivative (NH2eCeNH2),
which has a value of ꢀ62 ppm.22b However, our calculations
showed high positive values of siso (about 95 ppm) indicating
a strong character of nitrilimines for the intermediates obtained
from 1. These findings were comparable to the experimental 13C
chemical shifts observed for stabilized nitrilimines,24 ranging from
45 to 86 ppm, where, for example, ditritylnitrilimine,
(Ph3CeCNNeCPh3) had the largest experimental value, 86 ppm.
The predicted chemical shift (diso) of the parent nitrilimine 10 is
66 ppm and C-substitution produces a deshielding of the nitrili-
mine carbon nucleus (Table 2).24 This tendency agrees with our
observations obtaining a decrease in siso of about 30 ppm in the
evaluated nitrilimines. The small difference observed in the
deshielding of acroleinyl (1aed) and butadienyl (1f) derivatives
could be explained by a similar conjugated system in both
intermediates.
In addition, Table 2 depicts the Highest Occupied Molecular
Orbital (HOMO) of all calculated species. The carbon lone pair
character is obvious in the HOMO from left to right and is consistent
with the observed increase in carbene character.
Some calculations were also performed to provide information
about the origin of the anilines 6eef in the thermal reaction of
1eef. Table 3 illustrates the bond distances of nitrilimine moiety for
all compounds studied. All parameters, including the dihedral an-
N
N
N
N
N
N
R1
R1
a
R1
b
R1
c
d
Fig. 3. Representation of nitrilimine 2 by propargyllic (a), allenic (b), allylic (c) and
carbenic (d) structures.
The optimized parameters found in our calculations were
compared with values previously described for other nitrilimines
shown in Fig. 4: the parent formonitrilimine HeCNNeH (10), the
borane derivative HeCNNeBH2 (11), the diamine NH2eCNNeNH2
(12) and fluorinated derivatives FeCNNeF (13) and FeCNNeH (14).
The results are summarized in Table 2.
Y
N N
X
10, X= Y= H
11, X= H, Y= BH2
12, X= NH2, Y= NH2
13, X= F, Y= F
gle qYCN (Table 2), showed that nitrilimine (iv) from compound 1f,
was different and presented short AreN and N^C bond distances
and longer NeN and CCeC bond distances than nitrilimines formed
from 1aed. The weakness of these bonds could indicate why the
intermediates (iv) afforded anilines 6eef instead of the corre-
sponding indazole rings (Scheme 3).
14, X= H, Y= F
Fig. 4. Some variously substituted nitrilimines for comparative purposes.
By analyzing the values of YCN and CNN angles it was clearly
observed that the geometry of the intermediates corresponds to the
planar Cs structure with a greater contribution of species a, b and c,
In view of these interesting findings we can estimate that in
the FVP of butadienyltetrazoles (Scheme 3), both proposed ways
(a and b) would take place. In the case of fragmentation b the

1304
P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
Table 2
Calculations data for nitrilimines from azolyl derivatives 1 compared to data reported in the literature for nitrilimines 10e14
[a4b4c4d] YeCNNeX
Y
Acrol.
p-FPh
(1d)a
Acrol.
p-ClPh
(1c)a
Acrol.
Acrol.
p-i-pPh
(1a)a
H
Butad.
EtOC(O)
(1f)a
H
F
F
NH2
NH2
(12)b
X
p-OCH3Ph
(1b)a
BH2
(11)b
H
(10)b
H
(14)b
F
From
(13)b
C1
Cs
5.4
0
5.9
0
5.7
0
5.5
0
6.0
0
177
174
d
2.1
0
0
0
0
0
1.7 (TS)
133
170
d
14.5 (TS)
123
163
d
25.0 (TS)
117
159
d
12.0 (TS)
117
132
d
qYCN
qCNN
qNNX
179.2
172.4
117.6
aþbþc
95.7
92.3
179.2
172.1
117.6
aþbþc
95.5
92.5
179.4
172.5
117.8
aþbþc
94.7
93.3
179.3
172.4
117.6
aþbþc
95.3
92.7
176.6
172.6
117.3
aþbþc
96.4
91.6
H Contribution
siso
aþbþc
124.0
64.0
aþbþcþd
122.0
66.0
bþcþd
76.0
112.0
bþcþd
ꢀ11.0
199.0
bþd
ꢀ53.0
241.0
diso
HOMO
a
Zero-point energy corrected relatives energies (
D
E) in Kcal molꢀ1, bond angles in
q
degrees, absolute chemical shielding (siso) and chemical shifts (diso) in ppm reference to
TMS, calculated with GIAO/6-311þþG (2df,pd).
b
From reference 22.
4. Experimental part
4.1. General methods
Table 3
ꢁ
Bond distances (A) for all intermediates studied, calculated by B3LYP/6-311þþG
(2df,pd) method
AreNeZ^CeCH]CHeCH]G (Z¼N,C and G¼O, CH2)
FVP reactions were carried out in a Thermolyne 21100 furnace
using a vycor glass of 30 cm long and a 1.2 cm i.d. reactor. Tem-
peratures were 250e400 ꢁC, pressures of 10ꢀ2 Torr, contact times
were 10ꢀ2 s and sample amounts were 15e25 mg. After the ex-
periments were completed, the pyrolysate was extracted with or-
ganic solvents and submitted to purification and conventional
analysis (1H NMR, 13C NMR and GC/MS). Infrared spectra were
recorded at room temperature with a Nicolet 5SXC-FT IR spec-
trometer. 1H, 13C NMR spectra were recorded on a Bruker FT-200
(1H at 200, 13C at 50 MHZ) spectrometer. Chemical shifts are re-
ported in parts per million (ppm) downfield from TMS. Melting
points are uncorrected. Gas chromatography/mass spectrometry
(GC/MS) analyses were performed in a Shimadzu CG-MS-QP 5050A
spectrometer equipped with a VF column, using Helium as eluent at
a flow rate of 1.1 mL/min with a heating ramp of 15 ꢁC/min from
50 ꢁC to 280 ꢁC. Mass spectra were obtained in electron impact
mode (EI) with 70 eV ionization energy. Column and thin-layer
chromatograms were performed on silica gel. The exact mass
measurements were performed using a Q-TOF Premier mass
spectrometer (Waters Corporation, 34 Maple St, Milford, MA, USA)
in positive electrospray mode.
From
AreN
NeZ
Z^C
ZCeC
C]C
CHeCH
CH]G
NeN
N^C
1.178
1.179
1.179
1.180
N^C
1.174
NNeC
1.394
1.393
1.392
1.391
CCeC
1.403
CH]O
1.222
1.222
1.223
1.224
1c
1d
1a
1b
1.405
1.407
1.408
1.407
1.256
1.255
1.254
1.253
NeN
1.364
1.365
1.336
1.367
1.460
1.460
1.458
1.456
CH]CH2
1.348
1f
2
1.395
1.374
1.268
1.363
1.390
1.445
1.452
N]C
1.339
CeC:
1.359
C:eC
1.366
CH]O
1.226
formation of nitrilimine (vi) could be supported by the long bond
ꢁ
distance (1.403 A) found for the simple CeC bond in the fragment
ZCeC. On the other hand, the rupture a was corroborated by the
formation of conjugated nitriles, which were detected by GC/MS
analysis in the volatile fraction of the pyrolysate.
Besides, bond distance calculations for the carbenic in-
termediate allowed us to explain some features of the thermal re-
action. Looking at the results in the last entry of Table 3 we can see
that the N]C bond is longer than the NeN bond found for nitrili-
mine intermediates. However, the scission of this bond was not
achieved and the formation of all products could be explained by
the intermediacy of carbene species viii and their rearrangements.
It was further observed that the similar short bond distances in the
conjugated system for carbene species (vii) prevented fragmenta-
tion, thus allowing two competitive reactions: CeH aromatic in-
sertion and CeO addition.
4.1.1. (2E)-3-(5-Isopropyl-1H-indazol-3-yl)acrylaldehyde (3a). This
compound was obtained from FVP reaction of (2E)-3-[2-(4-
isopropylphenyl)-2H-tetrazol-5-yl]acrylaldehyde (1a) at tempera-
ture 350e370 ꢁC, yellow crystals, mp 127e129 ꢁC; nmax (KBr) 3147,
2958, 2820, 1686, 1452, 1379, 1360, 1352 cmꢀ1
; dH (200 MHz ace-
tone-d6) 12.18 (s, 1H, NH), 9.87 (d, 1H, J¼7.7 Hz, H30), 7.97 (d, 1H,
J¼16.1 Hz, H10), 7.94 (s, 1H, H4), 7.61 (dd, 1H, J¼8.8 and 0.7 Hz, H7),
7.42 (dd, 1H, J¼8.8 and 1.5 Hz, H6), 7.01 (dd, 1H, J¼16.4 and 7.7 Hz,
H20), 3.13 (sep., 1H, J¼6.9 Hz, CH i-Pr), 1.33 (d, 6H, J¼6.9 Hz, 2 CH3);
dC (50 MHz acetone-d6) 194.3, 161.3, 145.0, 144.4, 141.8, 141.4, 129.5,
127.4, 123.0, 117.6, 111.7, 35.0, 24.7; HRMS: MHþ, found 215.1178.
C13H15N2Oþ requires 215.1179.
3. Conclusions
From a synthetic point of view, FVP of acroleinyltetrazoles
(1aed) proved to be an appropriate methodology to obtain the
hitherto unknown acroleinylindazoles (3aed).
In the thermal reactions of tetrazoles (1aef) the nitrilimine
nature rather than the carbenic character of the intermediate was
proposed. Theoretical calculations showed that Cs structure was
4.1.2. (2E)-3-(5-Methoxy-1H-indazol-3-yl)acrylaldehyde (3b). This
compound was obtained from FVP reaction of (2E)-3-[2-(4-
methoxyphenyl)-2H-tetrazol-5-yl]acrylaldehyde (1c) at tempera-
ture 250e300 ꢁC and was not isolated from the reaction mixture.
Yellow thick oil; GC/MS: m/z (%)¼202 (91) [Mþ], 174 (87), 173 (100),
159 (72), 145 (22), 131 (45); nmax (KBr) 3160, 2926, 2837, 1687, 1616,
more stable than C1 and
C structures in the calculated
intermediates.

P.L. Lucero et al. / Tetrahedron 68 (2012) 1299e1305
1305
1513, 1496, 1259, 1114 cmꢀ1
;
dH (400 MHz CDCl3): 13.96 (s, 1H, NH),
References and notes
9.76 (d, 1H, J¼7.8 Hz, H30), 7.83 (d, 1H, J¼16.3 Hz, H10), 7.45 (d, 1H,
J¼9.0 Hz, H7), 7.21 (dd, 1H, J¼2.3 Hz, H4), 7.12 (dd, 1H, J¼9.0 and
2.0 Hz, H6), 6.97 (dd, 1H, J¼16.3 and 7.8 Hz, H20), 3.90 (s, 3H, OCH3);
dC (100.6 MHz CDCl3): 193.5, 156.3, 143.0, 142.9, 139.2, 138.6, 126.3,
125.4, 118.0, 112.3, 56.6; HRMS: MHþ, found 203.0816. C11H11N2Oþ2
requires 203.0815.
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chlorophenyl)-2H-tetrazol-5-yl]acrylaldehyde (1c) at temperature
250e300 ꢁC, brownish crystals, mp 106e107 ꢁC; nmax (KBr) 3146,
2847, 1654, 814 cmꢀ1. GC/MS: m/z (%)¼206 (32)[Mþ], 178 (100), 152
(26), 125 (11), 115 (27), 89 (19), 63 (28); dH (200 MHz DMSO-d6)
14.00 (s, 1H, NH), 9.76 (d, 1H, J¼8 Hz, H30), 7.95 (s, 1H, H4), 7.80 (d,
1H, J¼16 Hz, H10), 7.50 (d, 1H, J¼9 Hz, H7), 7.45 (dd, 1H, J¼9 and
2 Hz, H6), 7.02 (dd, 1H, J¼16.8 and 8 Hz, H20); dC (50 MHz DMSO-d6)
194.4, 143.6, 139.9, 135.6, 130.8, 128.6, 127.2, 122.3, 119.6, 112.7;
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fluorophenyl)-2H-tetrazol-5-yl]acrylaldehyde (1d) at temperature
250e280 ꢁC, colourless crystals, mp 91e92 ꢁC; nmax (KBr) 3090,
2850, 1720, 1641, 1275, 1217 cmꢀ1
; dH (200 MHz DMSO-d6) 13.96 (s,
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1H, NH), 9.70 (d, 1H, J¼7.8 Hz, H30), 7.99 (d, 1H, J¼16.1 Hz, H10), 7.90
(dd, 1H, J¼9.3 and 2.4 Hz, H8), 7.68 (dd,1H, J¼9.3 and 4.4 Hz, H7),
7.34 (td, 1H, J¼9.3 and J¼2.4 Hz, H-6), 6.95 (dd, 1H, J¼16.1 and
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C10H8FN2Oþ requires 191.0615.
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Acknowledgements
Thanks are due for the financial support provided by National
Research Council of Argentina (CONICET), Secretariat of Science
and Technology (SECyT) for the joint ArgentinedHungary project.
P.L.L. thanks CONICET for her doctoral fellowship. We are also
grateful to Dr. Marta Paleo for her contribution to this work. The
Hungarian Scientific Research Fund OTKA-NK 77784 is gratefully
acknowledged.
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Supplementary data
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Supplementary data (general experimental procedures and data
for compounds 7, 8 and 9) as well as computational data are found.
Supplementary data related to this article can be found, in the
online version, at doi:10.1016/j.tet.2011.11.034.
ꢀ
ꢀ
Mendez, L. Y.; Sortino, M.; Vasquez, Y.; Gupta, M. P.; Freile, M.; Enriz, R. D.;
Zacchino, S. A. Bioorg. Med. Chem. 2008, 794.