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C.D. Della Rosa et al. / Journal of Molecular Structure 1079 (2015) 47–53
The GEDT that fluxes from the ER diene framework to nitro-
TSs have one and only one imaginary frequency. The IRC paths
[25] were traced in order to check the energy profiles connecting
each TS to the two associated minima of the proposed mechanism
using the second order González–Schlegel integration method [26].
Solvent effects of benzene were taken into account through single
point energy calculations using the polarisable continuum model
(PCM) as developed by Tomasi’s group [27] in the framework of
the self-consistent reaction field (SCRF) [28]. The 6-311G⁄ basis
set was used in the PCM calculations. The electronic structures of
stationary points were analyzed by the natural bond orbital
(NBO) method [29]. All computations were carried out with the
Gaussian 09 suite of programs [30].
benzothiophenes ones along these P-DA reactions is 0.31e (TS2)
and 0.30e (TS2), These significant values point to the polar nature
of these cycloaddition reactions. As commented before, in spite of
the large polar character of these reactions, the loss of the aroma-
ticity along the nucleophilic attack on the aromatic ring is respon-
sible for high activation energies associated with these polar
reactions.
Conclusions
The reactions between 2- and 3-nitrobenzothiophene 1a y 1b
and different dienes, 2–4, developed in benzene as solvent to yield
dibenzothiophene and dibenzothiophenes derivatives 5–9 permit
to conclude that a properly substituted benzothiophene functions
as a normal dienophile with an activated 1,3-butadiene. However
when 1a and 1b were heated with less reactive isoprene it gave
the corresponding pyrrolyl-thiophenes 7 and 9 in low yield as
the single product formed by an assumed hetero cycloaddition
followed by thermal rearrangement. With microwave irradiation
and benzene as reaction media, 1a and 1b react with 2, 3 and 4,
respectively, to yield the same products than before. Reaction of
dienes 2 and 3 with nitrobenzothiophenes 1a and 1b under micro-
wave irradiation in solvent-free condition give good yields of the
aromatic dibenzothiphenes through elimination of the nitro group
and subsequent aromatization.
The use of MW irradiation decreases the time of reaction for
similar yields. The behavior of nitrobenzothiophenes in these P-
DA reactions is very similar to nitrothiophene. The P-DA reactions
of nitrobenzothiophenes 1a and 1b with ER dienes 2–3 have been
theoretically studied using DFT methods. The presence of the EW
nitro group in these nitrobenzothiophenes increases remarkably
the electrophilicity of benzothiophene, making it possible their
participation in P-DA reactions towards strong nucleophilic dienes
as 3 and 4. Analysis of the Parr functions at both electrophilic and
nucleophilic reagents indicates that these P-DA reactions are com-
pletely regioselective. The reactions of nitrobenzothiophenes 1a
and 1b with ER dienes 2–3 are domino reactions that begin via
P-DA reactions. Analysis of the reaction paths associated with the
P-DA reactions of 1a or 1b with the ER diene 2 indicates that they
take place via a two-stage one-step mechanism associated with the
nucleophilic attack of the ER diene 2 on these nitrobenzothioph-
enes. In spite of the large GEDT found at the corresponding TSs,
the lost of aromatic character of the benzothiophene rises the
activation energies to 16.6 and 14.2 kcal/mol. However, the strong
exothermic character of these P-DA reactions makes the cycloaddi-
tion irreversible, favoring the formation of the dibenzothiophene 6
through a domino reaction.
The global electrophilicity index [15]
ing expression, = ( ), in terms of the electronic chemical
2/2
potential and the chemical hardness . Both quantities may be
approached in terms of the one-electron energies of the frontier
molecular orbital HOMO and LUMO, eH and eL, as
ꢂ (eH ꢁ eL)/2
and
ꢂ (eL ꢁ eH), respectively [31]. Recently, we introduced an
x, is given by the follow-
x
l
g
l
g
l
g
empirical (relative) nucleophilicity index N [16], based on the
HOMO energies obtained within the Kohn–Sham scheme [32],
and defined as N = EHOMO(Nu) ꢁ EHOMO(TCE). The nucleophilicity
is referred to tetracyanoethylene (TCE), because it presents the
lowest HOMO energy in a large series of molecules already inves-
tigated in the context of polar cycloadditions. This choice allows us
to handle conveniently a nucleophilicity scale of positive values.
Electrophylic Pþk and nucleophilic Pꢁk Parr functions [19], were
obtained through the analysis of the Mulliken atomic spin density
(ASD) of the radical anion and radial cation of the reagents. The
local electrophilicity indices [21], were evaluated using the follow-
ing expressions: xk = x
Pþk [19].
General procedure for the thermal reactions of
nitrobenzothiophenes
The temperature, the length of the reaction, and the diene/die-
nophile ratio were dependent on the starting material and are indi-
cated in Table 1. An ampule containing a solution of 1.0 mmol of
the dienophile and the required amount of diene in 1 ml of dry
benzene was cooled in liquid nitrogen, sealed (under nitrogen
atmosphere), and then heated with stir in a bath. After the reaction
time was completed, it was cooled once more in liquid nitrogen
and opened. The solution was evaporated and the residue purified
by column chromatography on silica gel or alumina using hexane/
ethyl acetate mixtures as eluent [3b].
General procedure for the MW irradiation reactions of
nitrobenzothiophenes
Microwave irradiation was performed in
a Anton Parr
General aspects
Monowave 300, microwave reactor in standard closed vessels.
The temperature, the length of the reaction, and the diene/dieno-
phile ratio were dependent on the starting material and are indi-
cated in Table 2. After the reaction time was completed, the
solution was evaporated and the residue purified by column chro-
matography on silica gel or alumina using hexane/ethyl acetate
mixtures as eluent.
1H and 13C NMR espectra were recorded with the deuterated
solvent as the lock and residual solvent as internal on 300 and
75 MHz FT-spectrometers, respectively; GC–MS analyses were
performed in an instrument equipped with a PE-5-type column.
IR spectra were recorded from NaCl cells. The silica gel and neutral
alumina used for chromatography were 70–230 mesh.
Computational details
Dibenzo[b,d]thiophen-2-ol (5)
DFT computations were carried out using the MPWB1K func-
tionals [22], together with the standard 6-31G⁄ basis set [23].
The optimizations were carried out using the Berny analytical
gradient optimization method [24]. The stationary points were
characterized by frequency computations in order to verify that
IR [cmꢁ1]: 3200, 1378, 1173. 1H NMR (CDCl3) d: 5.50 (br s, 1H),
7.66 (dd, 1H, J = 7.8 Hz, J = 2.1 Hz), 8.07–8.25 (m, 3H), 8.56 (d, 1H,
J = 8.0 Hz), 8.85 (dd, 1H, J = 8.1 Hz, J = 1.7 Hz), 9.19 (dd, 1H,
J = 7.9 Hz, J = 1.8 Hz). Anal. Calcd. for C12H8SO: C, 78.23; H, 4.37;
S. 17.40. Found: C, 78.51 H, 4.49; S, 17.56.