Azo-hydrazo conversion via [1,5]-hydrogen shifts. A combined experimental and theoretical study

Article abstract of DOI:10.1016/j.tet.2012.06.013

Azoalkenes 6e, 6g, 6h, and 8c underwent an easy azo-hydrazo conversion via a [1,5]-hydrogen shift yielding α,β-unsaturated hydrazones. The isomerization products were characterized through spectroscopic and spectrometric techniques. In order to understand

Full text of DOI:10.1016/j.tet.2012.06.013

Tetrahedron 68 (2012) 6902e6907
Contents lists available at SciVerse ScienceDirect
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journal homepage: www.elsevier.com/locate/tet
Azo-hydrazo conversion via [1,5]-hydrogen shifts. A combined experimental
and theoretical study
,
a
b
Edikarlos M. Brasil a, Rosivaldo S. Borges a, Oscar A.S. Romero a , Claudio N. Alves , Jose A. Saez ,
*
ꢀ
,
Luis R. Domingo b
*
a
ꢀ
ꢀ
Departamento de Química, Instituto de Ciencias Exatas e Naturais, Universidade Federal do Para, CP 11101, 66075-110, Belem, PA, Brazil
Departamento de Química Organica, Universidad de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain
b
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 April 2012
Received in revised form 1 June 2012
Accepted 5 June 2012
Available online 12 June 2012
Azoalkenes 6e, 6g, 6h, and 8c underwent an easy azo-hydrazo conversion via a [1,5]-hydrogen shift
yielding a,b-unsaturated hydrazones. The isomerization products were characterized through spectro-
scopic and spectrometric techniques. In order to understand the nature of the mechanism of these [1,5]-
hydrogen shifts, the transition state structures of the reactions were theoretically studied at the B3LYP/6-
31G(d,p) level. Substitution effects in the propenylazo system on the kinetic and thermodynamic pa-
rameters were analyzed. An electron localization function (ELF) analysis of the electronic structure of the
transition state structure associated with the azo-hydrazo conversion of the simplest 1-azopropene 6a
indicates that these [1,5]-hydrogen shifts have a two-stage one-step mechanism via pseudodiradical
transition states, in which a formal hydrogen atom is transferred. This finding allows us to reject the
pericyclic reaction model for these [1,5]-hydrogen shift reactions.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
involve the cis-1,3-pentadiene system.12e15 Studies at B3LYP/6-
31G(d) level of the 15HS reaction of cis-1,3-pentadiene 116e18 (see
The [1,5]-hydrogen shift (15HS) reaction was first described by
Wolinsky1 when he observed a possible hydrogen shift in cis-1,3-
pentadiene 1 and paid attention to its reaction mechanism (see
Scheme 1). This reaction, classified within the pericyclic reaction
model as a [1,5]-sigmatropic reaction, was one of the examples
employed by R.B. Woodward and R. Hoffmann2 to establish their
well known conservation of orbital symmetry theory, further
supported by the analysis of the first order kinetic isotopic effects
Scheme 1) concluded that this reaction takes place through a con-
certed transition state (TS), which is 32.9 kcal/mol higher than
trans-1,3-pentadiene,18 a value close to that obtained through 1H
NMR experiments.3
Only few studies about 15HS reactions in heterodienic systems
(eCH2eC]CeX]Y; X¼C,
N
and/or Y¼N, O) have been
reported.18e21
The azo-hydrazo
conversion of 1-
tosylazocyclohexene 2 into the tautomer cyclohex-2-enone tosyl-
hydrazone 3 was reported by Dondoni et al. (Scheme 2).22
According to Dondoni, this azo-hydrazo conversion can take place
in absence of a catalyst, but the polarity of the solvent has a low
effect on the reaction rate.22
(KIEs) made by Roth and Konig.3,4 Since then, the 15HS reaction has
€
become part of the organic chemist toolbox as an alternative path
to new synthetic methods.5e11
H
H
H
1
N
N
NH
N
Tos
Tos
Scheme 1.
2
3
Scheme 2. Azo-hydrazo conversion of 1-tosylazocyclohexene 2.
Although excellent theoretical studies involving [1,5]-
sigmatropic reactions have been carried out, most of them
The 15HS reactions of several substituted 1,3-pentadiene and
aza-1,3-pentadiene systems were studied by Saettel et al. using
density functional theory (DFT) methods at B3LYP/6-31G(d) level
* Corresponding authors. E-mail address: domingo@utopia.uv.es (L.R. Domingo).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.013

E.M. Brasil et al. / Tetrahedron 68 (2012) 6902e6907
6903
(see Scheme 3).18 For these 15HS reactions, which were classified as
sigmatropic shifts within the pericyclic reaction model, the sub-
stitution effects on the activation energy were analyzed. The au-
in Supplementary Data). Azoalkene 8c was obtained by van
Alphen’s method from its bromo derivative (see Section b in
Supplementary Data). Refluxing azoalkene 6e and indene under
nitrogen for 20 h trying to obtain their cycloadduct left, after sol-
vent removal, 7e as orange crystals as the only product.
Likewise, attempting to obtain the intramolecular DielseAlder
cycloadduct from azoalkene 6g by refluxing it in dry toluene under
nitrogen for 18 h, yielded an orange gum after solvent removal.
Treating this gum with ether to induce crystallization gave rise to
yellow crystals in quantitative yield after 15 h, which were identi-
fied as compound 7g.
thors observed that the decrease of the electron density of the
p
system destabilizes the aromatic TS and increases the activation
energy and vice versa. The activation energies computed for the
15HS reaction of cis-but-2-en-1-imine 4 and cis-N-methyleneprop-
1-en-1-amine 5, 25.5 and 32.3 kcal/mol, respectively (see Scheme
3), were lower than that for cis-penta-1,3-diene 1.18 On the other
hand, the isomerization of 4 is exothermic by ꢀ3.7 kcal/mol, while
for 5 is endothermic by 2.8 kcal/mol.
Again, stirring at room temperature azoalkene 6h and butylvinyl
ether for 24 h trying to obtain its cycloadduct, yielded an orange
gum after solvent removal, which turned into yellow crystals
characterized as 7h upon purification procedures. Therefore, in 6e,
6g, and 6h reactions, their corresponding 15HS products were
obtained rather than the expected cycloadducts. This fact indicates
that the 15HS process is favored over the cycloaddition reaction in
these azoalkenes.
Y
X
Y
X
H
H
4 X=N, Y=CH2
5 X=CH, Y=NH
Scheme 3.
Starting from 3-acetyl-3-bromodihydrofuran-2(3H)-one, azoal-
kene 8c was obtained as bright red crystals using van Alphen’s
method.23 Upon attempting to recrystallize 8c from etherehexane
and warming (39 ꢁC), the red solution turned yellow, making it
possible to quantitatively isolate a solid, identified as 9c, by filtra-
tion. Hence, 6e, 6g, 6h, and 8c azoalkenes easily experienced a 15HS
reaction to yield the corresponding hydrazo compounds 7e, 7g, 7h,
and 9c without catalyst by heating them in solvent.
Herein, we report a combined experimental and theoretical
approach to azoalkene systems undergoing azo-hydrazo conver-
sions through 15HS processes. The synthesized azocompounds 6e,
6g, 6h, and 8c easily underwent an azo-hydrazo conversion into
hydrazones 7e, 7g, 7h, and 9c, respectively (see Scheme 4). DFT
calculations of the 15HS reactions of azoalkenes 6aeg and 8aec to
yield the corresponding hydrazones 7aeg and 9aec were per-
formed in order to establish their mechanism and disclose the
substitution effect on the propenylazo moiety. The electron locali-
zation function (ELF) of the structures involved in the reaction path
associated with the isomerization of the simplest azopropene 6a
was analyzed in order to characterize the electronic reorganization
along the 15HS reaction and to establish the mechanism of this azo-
hydrazo conversion.
2.2. DFT study of the [1,5]-hydrogen shift at azoalkenes 6
and 8
In order to understand the mechanism of the 15HS reactions of
azoalkenes 6 and 8 to afford a,b-unsaturated hydrazones 7 and 9,
respectively, the corresponding reactions were studied using DFT
methods at the B3LYP/6-31G(d,p) level (see Scheme 4). Analysis of
the stationary points found along the potential energy surface (PES)
indicates that the hydrogen shift from the donor C5 carbon to the
acceptor N1 nitrogen of these azoalkenes takes place through
a two-stage one-step mechanism.24
R1
R1
R2
R2
O
O
3
3
R1
N2
N
R1
N2
N
N
N
N
N
4
4
5
O
O
1
1
5
H6
8
R2
H6
6
R2
H
9
R3
R3
H
7
The azoalkene N1]N2eC3]C4 framework can adopt a s-trans
or s-cis conformation (see Scheme 5). The s-trans conformation of
azoalkene 6a is 4.8 kcal/mol more stable than the s-cis one, but the
last conformation is required for the reaction to take place. Pres-
ence of a phenyl group at C3 (R2¼C6H5) in azoalkene 6c does not
modify this relative energy, 4.2 kcal/mol, due to the twist of the
phenyl ring relative to the N1]N2eC3]C4 system, 50.4ꢁ.
(a) R1=R2=R3=H
(b) R1=R3=H; R2=Me
(c) R1=R3=H; R2=C6H5
(a) R1=R2=H
(b) R1=H; R2= C6H5
(c) R1=Me; R2= C6H5
(d) R1=R2=H; R3=2,4-(NO2)2C6H3
(e) R1=H; R2=C6H5 ; R3=2,4-(NO2)2C6H3
(f) R1= CO2Et; R2=R3=H
(g) R1= CO2Et; R2=Me, R3=2,4-(NO2)2C6H3
(h) R1= CO2CH2CH=CH2; R2=Me, R3=2,4-(NO2)2C6H3
Scheme 4.
R2
R2
1
3
2. Results and comments
N
R1
R1
R3
N2
4
5
N
N
First, experimental results of the conversion of azoalkenes 6e,
6g, 6h, and 8c into -unsaturated hydrazones 7e, 7g, 7h, and 9c
R3
a,b
s-trans
s-cis
will be analyzed. Then, a DFT study of the mechanism of these 15HS
reactions will be done, including a discussion about the influence of
the propenylazo substituents on the kinetic and thermodynamic
data. Finally, an ELF analysis of the structures along the IRC of the
reaction of azoalkene 6a will be carried out in order to understand
the electronic reorganization along the 15HS reaction.
Scheme 5.
The activation energies associated with the 15HS reactions of
these azoalkenes range from 15.7 (TS6c) to 22.3 kcal/mol (TS8b)
(see Table 1) (activation energies relative to the s-cis conformations
are given). These energy barriers are lower than those for (Z)-but-2-
en-1-imine 4 and (Z)-N-methyleneprop-1-en-1-amine 5, 25.5 kcal/
mol and 32.3 kcal/mol, respectively.18 All processes are exothermic,
ranging from ꢀ4.4 (6f) to ꢀ16.9 (6e) kcal/mol.
2.1. Experimental results
Azoalkenes 6e, 6g, and 6h were generated through dehy-
drohalogenation of the corresponding 2,4-dinitrophenyl
hydrazones by stirring them in dichloromethane with anhydrous
sodium carbonate at room temperature or heating (see Scheme S1
An analysis of the energy results given in Table 1 indicates that
the effect of the substituents at N1, C3, and C4 (see Scheme 4), is

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E.M. Brasil et al. / Tetrahedron 68 (2012) 6902e6907
Table 1
energies are: ꢀ15.2 (7e), ꢀ5.9 (7g), and ꢀ4.7 (9c) kcal/mol. These
kinetic and thermodynamic data are in reasonable agreement
with the experimental results, where a complete transformation
upon moderate heating is observed (dichloromethane or toluene
reflux).
Relativea energies (
D
E) in gas phase and in DCM, and relative enthalpies (
DH), en-
tropies (
the [1,5]-hydrogen shifts on azoalkenes 6 and 8
DS), and free energies (D
G), computedb at 298.1 K and 1 atm associated with
DEvacuo Esolv
D
D
H
DS
DG
(kcal/mol)
(kcal/mol)
(kcal/mol)
(cal/mol K)
(kcal/mol)
Geometries of the optimized TSs associated with the 15HS re-
actions present quite similar N1eH6 and H6eC5 forming- and
TS6a
TS6b
TS6c
TS6d
TS6e
TS6f
TS6g
TS8a
TS8b
TS8c
7a
7b
7c
7d
7e
7f
7g
9a
9b
19.0
19.7
15.7
20.3
18.1
20.0
21.9
18.4
22.3
20.1
20.9
17.5
16.7
16.7
14.0
ꢀ2.9
ꢀ5.7
2.7
17.5
18.4
13.2
ꢁ
breaking-bond distances, ranging from 1.345 to 1.402 A (N1eH6)
ꢁ
and 1.300 to 1.344 A (H6eC5), respectively (see Figs. 1 and 2).
21.4
19.4
21.5
21.9
19.6
23.5
21.5
ꢀ8.0
ꢀ6.6
ꢀ10.1
ꢀ15.0
ꢀ17.8
ꢀ5.5
ꢀ9.7
ꢀ13.1
ꢀ7.7
ꢀ7.3
17.2
14.9
17.0
18.8
15.3
19.0
17.5
ꢀ5.3
ꢀ5.1
ꢀ6.9
ꢀ13.6
ꢀ16.2
ꢀ3.8
ꢀ6.0
ꢀ10.7
ꢀ5.6
ꢀ5.2
ꢀ7.8
ꢀ7.0
ꢀ4.6
ꢀ6.7
ꢀ5.7
ꢀ6.0
ꢀ5.3
ꢀ1.1
2.2
19.6
17.0
18.4
20.9
17.0
20.8
19.0
ꢀ5.6
ꢀ4.5
ꢀ8.9
ꢀ12.3
ꢀ15.2
ꢀ3.6
ꢀ5.9
ꢀ10.1
ꢀ5.2
ꢀ4.7
Looking at N1eH6 forming- and H6eC5 breaking bonds at the TSs
of both 6 and 8 15HS reactions, it can be seen that these processes
are slightly asynchronous, as NeH distances are always slightly
higher than CeH ones. Note that, in methylamine, the lengths of the
ꢁ
ꢁ
20.8
NeH bonds, 1.017 A, are shorter than the CeH ones, 1.095 A, at the
same computational level.
ꢀ6.6
ꢀ5.8
ꢀ8.8
ꢀ14.5
ꢀ16.9
ꢀ4.4
ꢀ6.5
ꢀ11.1
ꢀ5.9
ꢀ5.3
The extent of breaking- and forming-bonds at the TSs involved
in these 15HS reactions was analyzed using the Wiberg bond order
(BO) values (see Table 2).26 In all studied cases, the N1eH6 forming-
ꢀ6.6
4.4
3.2
0.6
0.3
1.7
1.6
1.6
9c
a
Relative to s-cis conformation of azoalkenes 6 and 8.
Frequencies scaled by 0.96.
b
moderate over the energy barriers, since different substitution
patterns render relatively small energy differences (note that the
15HS activation energy difference between TS6c and TS8b at Table
1 is 6.6 kcal/mol). Thus, a good example can be found when com-
paring the 15HS reactions of 6d and 6e, where changing R2 at C3
from a hydrogen to a phenyl group yields a decrease of ca. 2.3 kcal/
mol in their reaction barrier. Again, changing R2 from a hydrogen 8b
to a methyl group 8c, results in a decrease of ca. 1.5 kcal/mol. Fi-
nally, the difference between 6b and 6c is their substituent at C3
(methyl and phenyl, respectively) and their energy barriers differ
by ca. 2 kcal/mol. Therefore, the introduction of electron-releasing
groups at the C3 carbon of the azoalkene moiety results in
a slight reduction of the 15HS energy barrier.
The substitution effect on N1 is more difficult to rationalize,
since changing the substitution at N1 from a hydrogen 6a to an
electron-withdrawing 2,4-dinitrophenyl group 6d increases the
energy barrier by ca. 1.3 kcal/mol, and the change at N1 in 8 moiety
from hydrogen 8a to a phenyl group 8b, increases the barrier by
4 kcal/mol. Therefore, 2,4-dinitrophenyl and phenyl groups, al-
though having different electronic behaviors, render the same
qualitative effect on the 15HS energy barriers. Then, the electronic
delocalization (present at both 2,4-dinitrophenyl and phenyl
groups) may be the prevalent effect appearing in this position at the
azoalkene moiety.
The inclusion of solvent effects of dichloromethane (DCM)
through single point PCM calculations over the gas phase B3LYP/6-
31G(d,p) geometries does not modify the gas phase B3LYP/6-
31G(d,p) energies (see Table 1). In general, the activation energies
in DCM increase only between 0.7 and 1.7 kcal/mol, due to a better
solvation of azoalkenes than TSs. Similar results are observed in
[3þ2] cycloadditions with non-polar character, where dipoles are
better solvated than TSs.25
Inclusion of thermal corrections and entropies to electronic
energies decreases the activation free energies between 0.8 and
2.5 kcal/mol (see Table 1). This effect is mainly due to the low
activation entropies associated with these unimolecular processes,
between ꢀ2.9 and ꢀ7.8 kcal/mol K. Thus, the activation free en-
ergies associated with the experimental reactions are: 17.0 (TS6e),
20.9 (TS6g), and 19.0 (TS8c) kcal/mol, while the reaction free
Fig. 1. Geometries of the transition states TS6aeg associated with the [1,5]-hydrogen
shifts of azoalkenes 6aeg. The distances are given in A, while the H6eC5eC4eC3 di-
hedral angles are given in degrees.
ꢁ

E.M. Brasil et al. / Tetrahedron 68 (2012) 6902e6907
6905
2.3. ELF topological analysis of the bond-breaking and bond-
formation along the [1,5]-hydrogen shift on 1-((Z)-prop-1-
enyl)diazene 6a
The topology of the ELF of some selected points along the 15HS
reaction at the simplest azoalkene 6a was studied to obtain addi-
tional information about the electron density reorganization in
these reactions, and thus, to characterize the molecular mechanism
of these 15HS reactions (see Scheme 6).27 The populations of the
most relevant valence basins, N, of these structures are listed in
Table 3, where d1 stands for the C5eH6 distance and d2 for the
N1eH6 one.
H
H
N
N
5
6
H
TS6a
H
H N1
N2
6a
4
H N
N
3
7a
Scheme 6.
The electronic structure of azoalkene 6a, point I, d1¼2.41 and
ꢁ
d2¼1.09 A, shows two disynaptic basins, V(C4,C5) and V(N2,C3),
which integrate ca. 2 e each one, representing the corresponding
single bonds. Also, two disynaptic basins appear, namely V(C3,C4)
and V0(C3,C4), which integrate 1.90 and 1.64 e, respectively, and
correspond to the C3eC4 double bond. Only one disynaptic basin
V(N1eN2), with an electronic population of 2.27 e, is found in the
N1]N2 region. Two monosynaptic basins are found at N1 and N2
nitrogen, respectively, V(N1) and V(N2), with an electronic pop-
ulation of 2.70 e and 2.75 e, respectively.
On going from azoalkene 6a to TS6a, the first relevant change
ꢁ
takes place at point III, d1¼1.10 and d2¼1.93 A, where the two
disynaptic basins V(C3,C4) and V0(C3,C4) merge into only one
disynaptic basin V(C3,C4), which integrates ca. 3.50 e. Along the
IRC, the electronic population of V(C3,C4) decreases slowly to reach
an electronic population of 2.26 e at the hydrazoalkene 7a.
ꢁ
Fig. 2. Geometries of the transition states TS8aec associated with the [1,5]-hydrogen
shifts of azoalkenes 8aec. The distances are given in A, while the H6eC5eC4eC3 di-
hedral angles are given in degrees.
At point IV, d1¼1.32 and d2¼1.39 A, only changes of electron
ꢁ
population of the basins are observed. Thus, while the electronic
Table 2
Wiberg bond orders (BOs) at the TSs associated with the [1,5]-hydrogen shifts on
azoalkenes 6 and 8
Table 3
ELF valence basin populations of selected geometries from the IRC of [1,5]-hydrogen
shift of azoalkene 6a, together with the C5eH6 (d1) and N1eH6 (d2) distances and
BOs characterizing each point
BO(C5eH6)
BO(N1eH6)
TS1a
TS1b
TS1c
TS1d
TS1e
TS1f
TS1g
TS3a
TS3b
TS3c
0.46
0.47
0.47
0.47
0.48
0.46
0.46
0.48
0.45
0.45
0.38
0.38
0.37
0.33
0.31
0.39
0.36
0.36
0.36
0.36
I
II
III
IV
V
VI
VII
VIII IX
X
6a
TS6a
7a
d1
d2
1.093 1.099 1.100 1.322 1.357 1.481 1.525 1.649 1.805 2.456
2.415 1.952 1.925 1.392 1.354 1.222 1.177 1.075 1.035 1.023
BO(C5eH6) 0.91 0.86 0.85 0.50 0.46 0.30 0.25 0.14 0.08 0.01
BO(N1eH6) 0.01 0.05 0.05 0.35 0.39 0.53 0.58 0.68 0.75 0.82
V(N1,N2)
V(N2,C3)
V(C3,C4)
V0(C3,C4)
V(C4,C5)
V0(C4,C5)
V(N1)
2.27 2.26 2.23 1.85 1.79 1.71 1.69 1.64 1.60 1.45
2.03 2.13 2.14 2.53 2.57 2.66 2.73 2.93 3.07 3.22
1.90 1.96 3.50 3.02 2.98 2.81 2.75 2.50 2.31 2.26
1.64 1.57
2.06 2.05 2.03 2.37 2.43 2.63 2.68 3.35 1.78 1.78
1.65 1.68
2.75 2.83 2.84 3.06 3.04 2.11 2.04 1.98 1.95 1.99
2.70 2.65 2.66 2.86 2.89 2.85 2.84 2.83 2.74 2.79
0.81 1.75 1.88 1.99 2.04
bond has a lower BO value, ranging from 0.31 to 0.39, when com-
pared to the C5eH6 breaking bond, whose BO ranges from 0.45 to
0.48. Thus, these values indicate that the H6eC5 breaking-bond
process is more advanced than the N1eH6 forming-bond. In ad-
dition, the narrow range of the C5eH6 and N1eH6 BO values, in-
dicates that the substitution on the propenyldiazene system of
azoalkenes 6 and 8 does not produce an appreciable effect on the
molecular mechanism of these 15HS reactions.
V(N2)
V(N1,H6)
V(C5,H6)
V(C5)
2.01 1.94 1.93 1.66
0.76 0.70 0.66
V(H6)
0.84 0.88

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E.M. Brasil et al. / Tetrahedron 68 (2012) 6902e6907
population of the disynaptic basin V(C3,C4) decreases to 3.02 e, the
disynaptic basins V(C4,C5) and V(N2,C3) increase to 2.37 e and
2.53 e, respectively. On the other hand, the disynaptic basin
V(C5,H6) integrates 1.66 e.
forming-bond process between the C5 and N1 centers, through
a cyclic six-membered TS.
3. Conclusions
ꢁ
At TS6a, point V, d1¼1.36 and d2¼1.35 A, the most relevant
changes of the electronic structure of azoalkene 6a along the IRC
are observed. While the disynaptic basin V(C5,H6) disappears, in-
dicating the complete C5eH6 breaking bond, two new mono-
synaptic basins V(C5) and V(H6), which integrate 0.76 e and 0.84 e,
respectively, are created. These monosynaptic basins point to
a homolytic C5eH6 breaking bond. Consequently, the ELF topology
of TS6a indicates that the electronic structure of this TS corre-
sponds with a pseudodiradical species,28e30 in which ca. 1 e is lo-
cated at the donor C5 carbon atom and another one at the
transferring H6 hydrogen atom. TS6a divides the two stages of this
15HS reaction; while the C5eH6 bond breaks before TS6a, the
N1eH6 bond-formation takes place after passing TS6a. This rep-
resentation makes it possible to discard a simultaneous bonding
reorganization at the six-membered TS, as proposed by the peri-
cyclic reaction model.
a,b-Unsaturated hydrazones 7e, 7g, 7h, and 9c have been
obtained from their azoalkene precursors 6e, 6g, 6h, and 8c with
excellent yields via a 15HS reaction, just heating them without
catalyst. DFT calculations have been performed in order to ratio-
nalize the mechanism of these 15HS reactions and to disclose the
substitution effects on the kinetic and thermodynamic parameters
of the process. These reactions take place through a two-stage one-
step mechanism. Activation energies range from 15.7 to 22.3 kcal/
mol, being 19.0 kcal/mol for the simplest azoalkene 6a. The largest
acceleration is observed when C3 is substituted by a phenyl group
(6c). All these reactions are exothermic. Inclusion of solvent effects
increases the activation energies slightly due to a stronger solvation
of azoalkenes than of the corresponding non-polar TSs.
ELF analysis of some relevant points along the IRC from the
simplest azoalkene 6a to the a,b-unsaturated hydrazone 7a allows
ꢁ
At point VI (d1¼1.48 and d2¼1.22 A), while the electron pop-
for the characterization of the electron-reorganization along this
15HS reaction. The most relevant changes take place at TS6a. ELF
analysis of the TS evidences that the reaction takes place through
a hydrogen atom transfer process from the donor C5 to the acceptor
N1 via a pseudodiradical species, which is achieved by a homolytic
CeH breaking bond. Thus, while the CeH bond has already been
broken at TS6a, the NeH bond has not been formed yet.
The ELF representation for the electron-reorganization along
these [1,5]-hydrogen shifts, which is characterized as a hydrogen
atom migration between the two extremes of a azoalkene, allows us to
reject a sigmatropic rearrangement process, defined within the
pericyclic reaction model as a reorganization of electrons during,
ulation of the monosynaptic basin V(N1) decreases by 0.93 e, a new
disynaptic basin V(N1,H6), with an electron population of 0.81 e,
emerges. This basin is associated with the formation of the new
N1eH6 bond. Note that at this point, the V(C5) and V(H6) mono-
ꢁ
synaptic basins coexist. At point VII (d1¼1.53 and d2¼1.18 A), the
monosynaptic basin V(H6) disappears, the corresponding electron
density being collected in the disynaptic basin V(N1,C6), which
reaches an electron density of 1.75 e.
ꢁ
At point VIII, d1¼1.65 and d2¼1.08 A, the monosynaptic basin
V(C5) disappears while the electron population of the disynaptic
basin V(C4,C5) reaches 3.35 e. Finally, at point IX, d1¼1.81 and
ꢁ
d2¼1.04 A, the disynaptic basin V(C4,C5) disassociates into two
which an atom or group attached by a
s
bond migrate to the other
disynaptic basins V(C4,C5) and V0(C4,C5), which integrate 1.78 e
and 1.65 e, respectively. They are associated with the C4]C5 dou-
ble bond present at the hydrazoalkene 7a. Finally, the more rele-
vant features of the hydrazoalkene 7a are the two disynaptic basins
V(C4,C5) and V0(C4,C5), which integrate 1.78 and 1.68 e, re-
spectively, the disynaptic basins V(C3,C4) and V(N2,C3), which in-
tegrate 2.26 e and 3.22 e, respectively, and two monosynaptic
basins V(N1) and V(N2), which integrate 1.99 and 2.79 e, re-
spectively. ELF analysis of the hydrazoalkene 7a displays a conju-
gated N2eC3eC4eC5 system, strongly polarized toward the N2
nitrogen atom.
terminus of a conjugate
p
-electron with a simultaneous shift of the
p
electrons.31
Acknowledgements
The authors would like to thank CAPES and CNPq from the
Brazilian Government and the Spanish Government (project
CTQ2009-11027/BQU) for their financial support.
Supplementary data
From this ELF analysis it can be concluded that along the 15HS
reaction of azoalkene 6a, the most significant changes of the
breaking- and forming-bond processes take place at two well
characterized points of the IRC: (i) at point V, d1¼1.36 and
Detailed procedures and full characterization of all synthetic
products are provided along with computational methods used in
the theoretical study. Supplementary data associated with this ar-
ticle can be found, in the online version, at http://dx.doi.org/
10.1016/j.tet.2012.06.013.
ꢁ
d2¼1.35 A, which corresponds to TS6a, where the disynaptic basin
V(C5,H6) disappears, indicating that the C5eH6 bond has been
broken, and two new monosynaptic basins, V(C5) and V(H6), ap-
pear. This behavior points to an initial homolytic C5eH6 breaking
bond with formation of a pseudodiradical species and (ii) at point VI,
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