Microwave-Assisted synthesis under solvent-free conditions of (E)-2-(Benzo[d]thiazol-2-yl)-3-arylacrylonitriles

Article abstract of DOI:10.1590/S0103-50532011001200022

A series of (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles was synthesized by microwave assisted Knoevenagel condensation under solvent-free conditions from the corresponding 2-(benzo[d]thiazol-2-yl)acetonitrile and aromatic aldehydes with electrondona

Full text of DOI:10.1590/S0103-50532011001200022

J. Braz. Chem. Soc., Vol. 22, No. 12, 2396-2402, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Short Report
S
Microwave-Assisted Synthesis under Solvent-Free Conditions of
(E)-2-(Benzo[d]thiazol-2-yl)-3-arylacrylonitriles
Jorge E. Trilleras,*, a Kelly J. Velasquez,a Dency J. Pacheco,a Jairo Quirogab and
Alejandro Ortízb
aGrupo de Investigación en Compuestos Heterocíclicos, Programa de Química,
Facultad de Ciencias Básicas, Universidad del Atlántico, Km 7 Antigua vía Puerto Colombia,
Barranquilla-Atlántico, Colombia
bGrupo de Investigación de Compuestos Heterocíclicos, Departamento de Química,
Universidad del Valle, A. A 25360 Cali, Colombia
Uma série de (E)-2-(benzo[d]tiazol-2-il)-3-arilacrilonitrilas foi sintetizada pela condensação
de Knoevenagel assistida por microondas, na ausência de solvente, partindo do correspondente
2-(benzo[d]tiazo-2-il)acetonitrila e aldeídos aromáticos, contendo tanto grupos doadores de
elétrons, como retiradores. Os tempos de reação foram consideravelmente curtos e os produtos,
obtidos em rendimentos moderados (50-75%) e boa pureza. A configuração da dupla ligação da
acrilonitrila não pôde ser estabelecida por métodos comuns de RMN. No entanto, estudos teóricos
sugerem que nesses compostos o isômero E é mais estável do que o Z, o que está de acordo com
algumas evidências experimentais.
A series of (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles was synthesized by microwave
assisted Knoevenagel condensation under solvent-free conditions from the corresponding
2-(benzo[d]thiazol-2-yl)acetonitrile and aromatic aldehydes with electrondonating/electron-
withdrawing groups. The reaction times were considerably short and the products obtained in
moderate yields (50 to 75%) and good purity. The configuration of the acrylonitrile double bond
could not be established by regular NMR methods. However, theoretical studies suggest that the
E isomer is more stable than Z, which is in good agreement with some experimental evidences.
Keywords: acrylonitriles, 2-(benzo[d]thiazol-2-yl)acetonitrile, solvent-free reaction, irradiation
microwave, Knoevenagel condensation, benzaldehydes
Introduction
that heteroaromatic acetonitrile derivatives undergo
Knoevenagel condensation reactions with arylaldehydes
to yield 3-aryl-2hetarylacrylonitriles.1-3,5-9 Substituted
acrylonitriles have been found to possess interesting
biological properties, among them, antifungal and
antitumor activities.7,10,11 Although acrylonitrile derivatives
are an-easy-to synthesize template, a great diversity
of the methods is available in literature that describe
their synthesis under different conditions making use of
conventional thermal energy and microwave irradiation
conditions.1-3,12-17 Typically, Knoevenagel adducts have
been obtained under conventional heating conditions for
extended periods of reaction in the presence of catalytic
amounts of base, obtaining generally from good to very low
yields.18-23 Condensation reactions leading to heterocyclic
systems have been performed with great success under
Acetonitrile derivatives are convenient precursors
which have been extensively utilized in heterocyclic
synthesis. Several reactions were developed in the last
decades for which the reactivity of hetarylacetonitriles
towards diverse reagents was exploited for the synthesis
of nitrogen bridged heterocycles.1-3 From the point of
view for biological activities, acetonitrile derivatives are
useful intermediates and subunits for the development of
molecules having pharmaceutical or biological interests.4-6
Nitrogen containing heteroaromatic compounds have
received considerable attention in the literature over the
years. From the synthetic point of the view, it is known
*e-mail: jorgetrilleras@mail.uniatlantico.edu.co

Vol. 22, No. 12, 2011
Trilleras et al.
2397
microwave irradiation in “dry media” reducing substantially
the reaction times and increasing product yields.24-26
Because of the advantages that microwave irradiation
has over conventional reflux methods, we present, herein,
the Knoevenagel synthesis of 3-arylacrylonitriles by
the reaction of 2-(benzo[d]thiazol-2-yl)acetonitrile with
different substituted arylaldehydes. The synthesis has
been assisted by microwave irradiation and under solvent-
free conditions. When compared with other methods,
this one has better yields, milder reaction conditions and
easy work-up, in addition to inexpensive reagents, and an
environmentally friendly procedure.
than hours when compared with conventional thermal
synthesis.18-23 This type of condensation reaction represents
a great potential for the synthesis of heterocyclic compounds
with possible biological activity. The fast reaction times,
combined with the easy purification and improved yields
make this method highly suitable. The synthesis of
products consists in irradiating the heterogeneous mixture
of 2-(benzo[d]thiazol-2-yl)acetonitrile 1 with different
substituted arylaldehydes 2 through reactions that are
conducted with neat solid reagents without catalysts;
elevation of the temperature had some positive effects
and improved the yield of the target product. Due to the
dipolar polarization phenomenon, the greater the polarity
of a molecule the more pronounced the microwave effect
when the rise in temperature is considered. In terms of
reactivity, the specific effect has therefore to be considered
according to the reaction mechanism and particularly with
regard to how the polarity of the system is altered during
the progress of the reaction.12
In initial attempts, we carried out the reaction under
solvent-free conditions during 15-20 min of microwave
irradiation in a commercial domestic oven, and then
the reactions conditions were optimized in a focused
microwaves reactor (CEM Discover TM) twice. In order to
improve our initial attempts, different reaction times, power
and temperatures were studied for the preparation of (E)-2-
(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3. The reaction
Results and Discussion
Microwave enhanced synthesis of (E)-2-(benzo[d]
thiazol-2-yl)-3-arylacrylonitriles 3a-j was carried out
under solvent-free conditions using different substituted
arylaldehydes 2 as shown in Scheme 1 and Table 1.
The reactions proceeded quite well with different
substituted aldehydes with electrondonating/electron-
withdrawing groups giving moderate yields (50 to 75%).
The condensation between 2-(benzo[d]thiazol-2-yl)
acetonitrile 1 and different substituted arylaldehydes 2
yields (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3 in
“dry media” conditions in excellent purities and moderate
yields. Reaction times were reduced to minutes rather
O
4'
1
CN
Ar
H
5'
6'
S
CN
N
S
2a-j
2'
2
MW
N
Ar
3
7'
3a-j
1
Scheme 1. Microwave irradiation synthesis under solvent-free conditions of (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3a-j.
Table 1. Knoevenagel reaction between 2-(benzo[d]thiazol-2-yl)acetonitrile (1) and aromatic aldehydes (2a-j)
Data reported in literature for compounds 3a-j18-23
Ar
time reaction / min
15/180
15/180
20/240
20/240
20/180
10
yield / (%)
70/46
70/54
50/50
75/51
50/54
50
mp / (ºC)
a
b
c
d
e
f
C6H5
4-H3C-C6H4
4-O2N-C6H4
4-Cl-C6H4
116-118/121-123
140-142/147-148
170-172/177-180
144-148/148-150
138-140/143-145
150-152
4-Br-C6H4
4-F-C6H4
g
h
i
4-F3C-C6H4
10/180
15/180
15
75/56
50/62
55
122-124/128-133
130-dec./143-144
140-142
4-H3COC6H4
3,4,5-tri-H3CO-C6H2
3,4-OCH2O-C6H3
j
15/180
50/40
192-194/200-205

2398
Microwave-Assisted Synthesis under Solvent-Free Conditions of Arylacrylonitriles
J. Braz. Chem. Soc.
J 8.03 Hz
carried under the maximum power 150W during 10-20 min
at a controlled temperature of 473 K and 250 psi proved to
be the most satisfactory.An increase in the irradiation time
did not affect the yields.
7.89
121.6
H
J 8.28 Hz
7.31
130.0
H
7.41
116.7
CN
J 8.29 Hz
J 8.28 Hz
140.1
125.8
H
H
1
S
163.0
104.4
All compounds were characterized on the basis
of their elemental analyses, mass and NMR spectral
data. The whole carbon skeleton was assigned using
13C NMR spectra, (including distortionless enhancement by
polarization transfer (DEPT)) and two dimensional HSQC
(heteronuclear single quantum correlation), and HMBC
(heteronuclear multiple bond correlation) experiments. The
(E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3a-j were
were characterized by a very polarized carbon-carbon double
bond (C2-C3), which leads to chemical shifts from 102.2 to
109.5 ppm for C2 and 143.2 to 146.9 ppm for C3; the signal
of CN at d values from 115.6 to 117.3 ppm; from 1H NMR,
a singlet between 8.12 and 8.30 ppm for H3 (Figure 1).
The 13C NMR spectra of all other compounds of
the series retain similar signals, differing only in those
corresponding to the aryl ring. Regarding to mass spectra,
all products 3 exhibit a similar pattern of fragmentation,
showing the molecular peak along with a typical loss of
the substituents of each aryl group.
2
129.7
2.43
21.8
143.4
CH3
N
7.51
126.8
134.9
3
H
H
8.07
123.5
8.20
146.9
H
7.93
HMBC Correlations
J 8.28 Hz
130.5
J 8.28 Hz
Figure 1. Structural formula of (E)-2-(benzo[d]thiazol-2-yl)-3-p-
tolylacrylonitrile 3b.
3-arylacrylonitrile derivatives it has also been observed
preference for the E isomer.7,13-15 Compound (3a) and (E)-
3-phenyl-2-(thiophen-2-yl)acrylonitrile (4) previously
reported by us,7 might have a number of conformations
due to free rotation around the double bond; the most
stable conformations are shown in Figure 2 and apparently
the lowest energy structure is favored by planarity of the
molecule around the double bond mentioned; this fact was
calculated by means theoretical methods like DFT using a
B3LYP functional and 3-21G as basis set.
The configuration of the acrylonitrile double bond
could not be established by NMR methods. However,
studies have shown that for these compounds the E isomer
is more stable than the Z. This result can be explained by
the steric and electronic repulsions between the aromatic
and heteroaromatic groups.27 In previous research on these
When performing an analysis of net atomic charges of
the most stable conformers, it was found that for conformer
3a, the presence of a hydrogen bond between the H3 and
N, is the driving force for greater stability and planarity;
these two atoms are at a distance of 2.399 Å, the H3 also
presents a net charge of 0.26556e and a valence of 0.73151
Figure 2. Lowest energy structures calculated for 3a and 4.

Vol. 22, No. 12, 2011
Trilleras et al.
2399
CN
N
S
H
N
CN
MW
N
CN
O
3a-j
Ar
Ar
H
-H2O
S
S
HO
A
1
2
Scheme 2. Plausible formation of Knoevenagel adducts assisted by microwave irradiation.
versus the average of the other protons in the molecule with
net charge 0.24834e and valence of 0.750091. The latter
fact is evidenced experimentally in the 1H NMR spectrum
for this compound, where the proton H3 is observed at
very low field d 8.25 ppm, because (as presented in this
NPA analysis) it is very deshielded compared to the other
protons. In the case of NPA analysis for conformer 4’, all
the charges on the protons are in an average; this means that
the possibility of hydrogen bonds is low. As a proof of this
fact, H3 for this molecule has a net charge 0.24035e and
a valence of 0.73710; average values for a proton gave no
such address as the deshielding effect, so that its stability
can be attributed more to his E-type configuration about
the double bond.
It seems reasonable to think that microwave irradiation
promotes the Knoevenagel reactions through the methylene
active component of 2-(benzo[d]thiazol-2-yl)acetonitrile 1.
Under the optimized reaction conditions, 1 is likely to
be converted to compound A containing double bond
susceptible to the addition of electrophile 2 (Scheme 2).
internal standard. The mass-spectra were scanned on a
Hewlett Packard HP Engine-5989 spectrometer (equipped
with a direct inlet probe) which was operating at 70 eV.
The elemental analyses have been obtained using a LECO
CHNS-900 and Thermo Finnigan FlashEA1112 CHNS-O
elemental analyzers. Thin layer chromatography was
carried out using Merck 0.2 mm silica gel 60F254 aluminum
chromatographic plates.
All theoretical calculations were carried out at the DFT
approach using the Gaussian 03 program review C.02.28 The
DFT calculations were determined using three parameters
exchange functional of Becke B3LYP and a set of orbital
3-21G basis. The net atomic charges were calculated using
NPA analysis included in the algorithm natural bonding
orbital (NBO) proposed by Weinhold and co-workers.29,30
Reagents
The reagents (2-(benzo[d]thiazol-2-yl)acetonitrile
and aromatic aldehydes) and solvents used, such as,
ethanol, ethyl acetate, hexane and DMF, were acquired
commercially.
Conclusions
We report here an efficient synthetic route to prepare (E)-
2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles derivatives
conducted by microwave irradiation under solvent-free
conditions. These conditions allowed us to obtain the
compounds in short times and acceptable yields. No
relationship was found between them and the nature of the
substituents of the aldehydes. Further efforts to expand the
scope of the chemistry on these compounds are ongoing
subjects in our laboratory.
Synthesis
General procedure for the preparation of the (E)-2-
(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3a-j
A mixture of 2-(benzo[d]thiazol-2-yl)acetonitrile 1
and aromatic aldehydes 2 with electrondonating/electron-
withdrawing groups (1 mmol) were subjected to microwave
irradiation (maximum power 150 W during 10-20 min
under solvent-free conditions at a controlled temperature
of 473 K and 250 psi) using a focused microwave reactor
(CEM Discover). The solid products were isolated by
simple crystallization of the reaction mixture from ethanol.
Experimental
Equipments
Microwave experiments were carried out using a
focused microwave reactor (CEM Discover TM). Melting
points were determined in a Buchi melting point apparatus
(E)-2-(Benzo[d]thiazol-2-yl)-3-phenylacrylonitrile 3a
Yellow solid; mp 116-118 °C, 70%. IR (KBr) νmax/cm-1:
2221 (CN), 3060 (-C=HAromatics), 3019 (=C-H), 1590
(C=C). MS (70eV) m/z (%): 263(9, M++1), 262(32, M+),
261(100), 236(13). H NMR (400 MHz, CDCl3) d ppm:
7.43 (t, 1H, J 8.28 Hz, Hp), 7.50-7.56 (m, 4H, H, phenyl),
7.91 (d, 1H, J 8.03 Hz, H7’), 8.01-8.04 (m, 2H, H5’ and
1
and are reported uncorrected. The H and 13C NMR
1
spectrum were measured at RT on a Bruker Avance 400
spectrometer operating at 400 and 100 MHz, respectively,
and using CDCl3 as solvent and tetramethylsilane as

2400
Microwave-Assisted Synthesis under Solvent-Free Conditions of Arylacrylonitriles
J. Braz. Chem. Soc.
H6’), 8.08 (d, 1H, J 7.76 Hz, H4’), 8.25 (s, 1H, CH).
13C NMR (100 MHz, CDCl3) d ppm: 105.7 (C2), 116.4
(CN), 121.7 (C4’), 123.7 (C7’), 126.0 (C6’), 127.0 (Cp),
129.3 (Cm), 130.4 (Co), 132.2 (Ci), 135.0 (C7’a), 147.0
(CH), 162.7 (C2’). Anal. calc. for C16H10N2S: C 73.26; H
3.84; N 10.68; found: C 73.16; H 3.83; N 10.65.
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-bromophenyl)
acrylonitrile 3e
Brown solid; mp 138-140 °C, 50%. IR (KBr) νmax/cm-1:
2219 (CN), 3062 (-C=HAromatics), 3020 (=C-H), 1579
(C=C). MS (70 eV) m/z (%): 341(17, M++2), 339(16, M+),
280(40), 279(100), 254(21). 1H NMR (400 MHz, CDCl3) d
ppm: 7.44 (t, 1H, J 7.28 Hz, H5’), 7.54 (t, 1H, J 7.03 Hz,
H6’), 7.64 (d, 2H, J 8.53, Hm), 7.87 (d, 2H, J 8.78 Hz, Ho),
7.91 (d, 1H, J 8.03 Hz, H4’), 8.08 (d, 1H, J 8.04 Hz, H7’),
8.18 (s, 1H, CH). 13C NMR (100 MHz, CDCl3) d ppm:
106.1 (C2), 116.2 (CN), 121.7 (C4’), 123.7 (C7’), 126.1
(C5’), 126.9 (Ci), 127.0 (C6’), 131.5 (Cm), 132.6 (Co),
135.0 (C7’a), 145.2 (CH), 153.4 (Cp), 162.3 (C2’). Anal.
calc. for C16H9BrN2S: C 56.32; H 2.66; N 8.21; found: C
56.33; H 2.63; N 8.17.
(E)-2-(Benzo[d]thiazol-2-yl)-3-p-tolylacrylonitrile 3b
Yellow solid; mp 140-142 °C, 70%. IR (KBr) νmax/cm-1:
2223 (CN), 3018 (-C=HAromatics), 2855 (=C-H), 1589
(C=C). MS (70 eV) m/z (%): 277(10, M++1), 276(40, M+),
275(100). 1H NMR (400 MHz, CDCl3) d ppm: 2.43 (s, 3H,
CH3) 7.31 (d, 2H, J 8.28, Hm), 7.41 (t, 1H, J 8.29 Hz, H5’),
7.51 (t, 1H, J 8.28 Hz, H6’), 7.89 (d, 1H, J 8.03 Hz, H4’),
7.93 (d, 2H, J 8.28 Hz, Ho), 8.07 (d, 1H, J 8.28 Hz, H7’),
13
8.21 (s, 1H, CH)). C NMR (100 MHz, CDCl3) d ppm:
21.8 (CH3), 104.4 (C2), 116.7 (CN), 121.6 (C4’), 123.5
(C7’), 125.8 (C5’), 126.8 (C6’), 129.7 (Ci), 130.0 (Cm),
130.5 (Co), 134.9 (C7’a), 140.1 (C3’a), 143.4 (Cp), 146.9
(CH), 163.0 (C2’). Anal. calc. for C17H12N2S: C 73.88; H
4.38; N 10.14; found: C 73.80; H 4.36; N 10.17.
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-fluorophenyl)
acrylonitrile 3f
Brown solid; mp 150-152 °C, 50%. IR (KBr) νmax/cm-1:
2224 (CN), 3052 (-C=HAromatics), 1588 (C=C). MS
(70 eV) m/z (%): 281(10, M++1), 280(39, M+), 279(100),
254(22). 1H NMR (400 MHz, CDCl3) d ppm: 7.19 (t, 2H,
J 8.53 Hz, Hm), 7.43 (t, 1H, J 7.02 Hz, H5’) 7.52 (t, 1H,
J 7.02 Hz, H6’), 7.90 (d, 1H, J 8.28 Hz, H4’), 8.02-8.07
(m, 3H, Ho, H7’), 8.20 (s, 1H, CH). 13C NMR (100 MHz,
CDCl3) d ppm: 105.2 (C2), 116.4 (CN), 116.7 (Cm),
121.7 (C4’), 123.6 (C7’), 126.0 (C5’), 127.0 (C6’), 128.7
(Ci), 132.7 (Co), 134.9 (C7’a), 145.3 (CH), 153.6 (Cp),
162.5 (C2’).
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-nitrophenyl)
acrylonitrile 3c
Yellow solid; mp 170-172 °C, 50%. IR (KBr) νmax/cm-1:
2225 (CN), 3031 (-C=H) 2853 (=C-H), 1522 (C=C). MS
(70 eV) m/z (%): 308(11, M++1), 307(46, M+), 306(82),
260(100), 261(38). 1H NMR (400 MHz, CDCl3) d ppm 7.46
(t, 1H, J 7.00 Hz, H5’), 7.55 (t, 1H, J 7.00 Hz, H6’), 7.77
(d, 2H, J 8.53 Hz, Hm) 7.93 (d, 1H, J 8.30 Hz, H4’), 8.10 (d,
3H, J 8.78 Hz, Ho, H7’), 8.29 (s, 1H, CH). 13C NMR (100
MHz, CDCl3) d ppm: 108.5 (C2), 116.2 (CN), 122.1 (C4’),
124.1 (C7’), 125.2 (Ci), 126.5 (C5’), 126.7 (C6’), 127.5
(Cm), 130.6 (Co), 133.3, 133.7 (C7’a), 135.5 (C3’a), 135.9
(Cp), 144.9 (CH), 153.9 (C2’). Anal. calc. for C16H9N3O2S:
C 62.53; H 2.95; N 13.67; found: C 62.54; H 2.92; N 13.72.
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)
acrylonitrile 3g
Beige solid; mp 122-124 °C, 75%. IR (KBr) νmax/cm-1:
2229 (CN), 3066 (-C=HAromatics), 2942 (=C-H), 1476
(C=C). MS (70 eV) m/z (%): 331(10, M++1), 330(38,
1
M+), 329(100), 304(13), 261(11). H NMR (400 MHz,
CDCl3) d ppm: 7.48 (t, 1H, J 7.03 Hz, H5’), 7.56 (t, 1H,
J 7.03 Hz, H6’), 7.93 (d, 1H, J 7.78 Hz, H4’) 8.10 (d, 1H,
J 8.04 Hz, H7’), 8.14 (d, 2H, J 8.79 Hz Ho), 8.30 (s, 1H,
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-chlorophenyl)
acrylonitrile 3d
Yellow solid; mp 144-148 °C, 75%. IR (KBr) νmax/cm-1:
2219 (CN), 3060 (-C=HAromatics), 2855 (=C-H), 1584
(C=C). MS (70 eV) m/z (%): 298(15, M++2), 296(42,
CH), 8.34 (d, 2H, J 8.78 Hz, Hm). C NMR (100 MHz,
13
CDCl3) d ppm: 109.5 (C2), 115.6 (CN), 121.80 (C4’), 124.0
(C7’), 124.3 (C5’), 126.6 (C6’), 127.3 (Cm), 130.8 (CO),
135.3 (C7’a), 138.0 (C3’a), 143.2 (CH), 161.2 (C2’).Anal.
calc. for: C 61.81; H 2.75; N 8.48; found: C 61.82; H 2.71;
N 8.49.
1
M+), 295(100), 270(17), 261(11). H NMR (400 MHz,
DMSO-d6) d ppm 7.51 (t, 1H, J 7.28 Hz, H5’), 7.58 (t, 1H,
J 7.53 Hz, H6’), 7.66 (d, 2H, J 8.79 Hz, Hm,) 8.07 (d, 1H,
J 7.53 Hz, H4’), 8.09 (d, 2H, J 9.03 Hz, Ho), 8.17 (d, 2H,
13
J 8.03 Hz, H7’), 8.40 (s, 1H, CH). C NMR (100 MHz,
(E)-2-(Benzo[d]thiazol-2-yl)-3-(4-methoxyphenyl)
acrylonitrile 3h
Yellow solid; mp 130 °C (decomposition); 50%. IR
(KBr) νmax/cm-1: 2219 (CN), 3007 (-C=HAromatics), 2833
(=C-H), 1589 (C=C). MS (70 eV) m/z (%): 293(13, M++1),
CDCl3) d ppm: 106.1 (C2), 115.8 (CN), 122.4 (C4’), 123.1
(C7’), 126.3 (C5’), 127.1 (C6’), 129.3 (Cm), 131.1 (Ci),
131.7 (Co), 134.3 (C7’a), 136.8 (C3’a), 146.7 (CH), 152.8
(Cp), 162.8 (C2’).

Vol. 22, No. 12, 2011
Trilleras et al.
2401
292(58, M+), 291(100), 277(11), 266(27), 261(13), 248(41).
1H NMR (400 MHz, CDCl3) d ppm: 3.87 (s, 3H, OCH3),
6.99 (d, 2H, J 8.79 Hz, Hm), 7.39 (t, 1H, J 8.03 Hz, H5’),
7.49 (t, 1H, J 8.03 Hz, H6’), 7.87 (d, 1H, J 8.03 Hz, H4’),
8.00 (d, 2H, J 8.79 Hz, Ho), 8.02 (d, 1H, J 8.28 Hz, H7’),
8.14 (s, 1H, CH). 13C NMR (100 MHz, CDCl3) d ppm: 55.8
(OCH3), 102.6 (C2), 115.0 (Cm), 117.3 (CN), 121.9 (C4’),
123.6 (C7’), 125.5 (Ci), 126.0 (C5’), 127.1 (C6’), 133.0
(Co), 135.1 (C7’a), 146.7 (CH), 153.9 (Cp), 163.2 (C2’).
Anal. calc. for C17H12N2OS: C 69.84; H 4.14; N 9.58; found:
C 69.86; H 4.15; N 9.55.
Acknowledgments
The authors thank Universidad del Atlántico,
Universidad del Valle (Colombia) and COLCIENCIAS
for financial support.
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B. F.; J. Heterocycl. Chem. 2010, 47, 243.
2. Quiroga, J.; Cruz, S.; Insuasty, B.; Abonía, R.; Nogueras, M.;
Sánchez, A.; Cobo, J.; Low, J. N.; J. Heterocycl. Chem. 2001,
38, 53.
(E)-2-(Benzo[d]thiazol-2-yl)-3-(3,4,5-trimethoxyphenyl)
acrylonitrile 3i
3. Quiroga, J.; Cruz, S.; Insuasty, B.; Abonía, R.; Heterocycl.
Commun. 2000, 6, 275.
Yellow solid; mp 140-142 °C, 55%. IR (KBr) νmax/cm-1:
2210 (CN), 3055 (-C=HAromatics), 2838 (=C-H), 1573
(C=C). MS (70 eV) m/z (%): 353(14, M++1), 352(53, M+),
4. Mavrava, A. T.; Anchina, K. K.; Vuchev, D. I.; Tesnove, J. A.;
Kondeva, M. S.; Miteka, K. M.; Bioorg. Med. Chem. 2005, 13,
5550.
1
357(37), 151(100). H NMR (400 MHz, CDCl3) d ppm:
3.93 (s, 6H, OCH3-Cm), 3.95 (s, 3H, OCH3-Cp), 7.31 (s,
2H, Ho), 7.41 (t, 1H, J 7.03 Hz, H5’), 7.51 (t, 1H, J 7.03 Hz,
H6’), 7.89 (d, 1H, J 7.03 Hz, H4’), 8.05 (d, 1H, J 7.28 Hz,
H7’), 8.15 (s, 1H, CH). 13C NMR (100 MHz, CDCl3)
d ppm: 56.3 (OCH3-Cm), 61.1 (OCH3-Cp), 104.0 (C2),
107.9 (Co), 116.9 (CN), 121.6 (C4’), 123.4 (C7’), 125.9
(C5’), 126.9 (6’), 127.5 (Ci), 134.9 (C7’a), 141.9 (C3’a),
146.7 (CH), 153.3 (Cm), 153.6 (Cp), 162.9 (C2’). Anal.
calc. for C19H16N2O3S: C 64.76; H 4.58; N 7.95; found: C
64.74; H 4.59; N 7.91.
5. Yildiz-Oren, I.; Yalcin, I.; Aki-Sener, E.; Ukarturk, N.; Eur. J.
Med. Chem. 2004, 39, 291.
6. Carta, A.; Palomba, M.; Boatto, G.; Busonera, B.; Murreddu,
M.; Loddo, R.; FARMACO 2004, 59, 637.
7. Quiroga, J.; Cobo, D.; Insuasty, I.; Abonía, R.; Nogueras, M.;
Cobo, J.;Vásquez,Y.; Gupta, M.; Derita, M.; Zacchino, S.; Arch.
Pharm. 2007, 340, 603.
8. Zhao, K.; Xu, X-P.; Zhu, S-L.; Shi, D-Q.; Zhang, Y.; Ji, S-J.;
Synthesis 2009, 16, 2697.
9. Thirumurugan, P.; Perumal, P. T.; Tetrahedron 2009, 65, 7620.
10. Hranjec, M.; Pavlovic, G.; Marjanovic, M.; Kralj, M.;
Karminski-Zamola, G.; Eur. J. Med. Chem. 2010, 45, 2405.
11. Refaat, H. M.; Eur. J. Med. Chem. 2010, 45, 2949.
12. Bougrin, K.; Loupy, A.; Soufiaoui, M.; J. Photochem.
Photobiol., C 2005, 6, 139.
(E)-3-(Benzo[d][1,3]dioxol-6-yl)-2-(benzo[d]thiazol-2-yl)
acrylonitrile 3j
Yellow solid; mp 192-194 oC, 50%. IR (KBr) νmax/cm-1:
2211 (CN), 3065 (-C=HAromatics), 2918 (=C-H), 1570
(C=C). MS (70eV) m/z (%): 307(14, M++1), 306(56,
13. Quiroga, J.; Trilleras, J.; Sánchez, A.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Cobo, J.; Lett. Org. Chem. 2009, 6, 381.
14. Quiroga, J.; Trilleras, J.; Gálvez, J.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Cobo, J.; Tetrahedron Lett. 2009, 50, 6404.
15. Gálvez, J.; Quiroga, J.; Cobo, J.; Low, J.; Glidewell, C.; Acta
Crystallogr., Sect. C: Cryst. Struct. Commun. 2008, 64, 385.
16. Hirata,Y.;Yada, A.; Morita, E.; Nakao,Y.; Hiyama, T.; Ohashi,
M.; Ogoshi, S.; J. Am. Chem. Soc. 2010, 132, 10070.
17. Tomioka, T.; Takahashi, Y.; Vaughan, T. G.; Yanase, T.; Org.
Lett. 2010, 12, 2171.
1
M+), 305(100), 280(16), 248(16). H NMR (400 MHz,
CDCl3) d ppm: 6.11 (s, 2H, CH2), 6.95 (d, 1H, J 8.03 Hz,
H5-aryl), 7.43 (t, 1H, J 8.28 Hz, H5’), 7.47 (d, 1H,
J 8.28 Hz, H6-aryl), 7.52 (t, 1H, J 8.28 Hz, H6’), 7.71 (s,
1H, H2-aryl), 7.93 (d, 1H, J 8.53 Hz, H4’), 8.03 (d, 1H,
J 8.03 Hz, H7’), 8.12 (s, 1H, CH). 13C NMR (100 MHz,
CDCl3) d ppm: 101.5 (CH2), 102.2 (C2), 107.6 (CH-aryl),
108.2 (CH-aryl), 115.9 (CN), 120.9 (C4’), 122.6 (C7’),
125.1 (C5’), 126.1 (C6’), 127.6 (CH-aryl), 134.0 (Cq),
146.0 (CH), 147.9 (Cq), 150.7 (Cq), 152.8 (Cq), 162.4
(C2’). Anal. calc. for C16H9N3O2S: C 62.53; H 2.95; N
13.67; found: C 62.54; H 2.92; N 13.62.
18. Fadda, A. A.; Hammouda, M.; Afsah, E. M.; Hanash, A. A.;
Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 433.
19. Fadda, A. A.; Zaki, M.; Samir, K.; Etman, H. A.; Phosphorus,
Sulfur Silicon Relat. Elem. 2008, 183, 1801.
Supplementary Information
20. Dryanska, V.; Phosphorus, Sulfur, Silicon Relat. Elem. 1991,
61, 325.
Supplementary information (Figures S1-S20) is
available free of charge at http://jbcs.sbq.org.br as PDF file.
21. Fathy, N. M.; Abdel Motti, F. M.; Elgemeie, G. E. H.; Arch.
Pharm. 1988, 321, 509.

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Microwave-Assisted Synthesis under Solvent-Free Conditions of Arylacrylonitriles
J. Braz. Chem. Soc.
22. Dryanska, V.; Sulfur Lett. 1986, 5, 47.
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Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala,
P.Y.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador,
P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Strain, M.
C.; Farkas, O.; Malick, D. K.; Rabuck,A. D.;Raghavachari, K.;
Foresman, J. B.; Ortiz, J.V.; Cui, Q.; Baboul,A. G.; Clifford, S.;
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko,A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez,
C.; Pople, A.; Gaussian 03, Revision C.02; Gaussian, Inc.:
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Submitted: March 17, 2011
Published online: September 6, 2011

J. Braz. Chem. Soc., Vol. 22, No. 12, S1-S15, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
Microwave-Assisted Synthesis under Solvent-Free Conditions of
(E)-2-(Benzo[d]thiazol-2-yl)-3-arylacrylonitriles
Jorge E. Trilleras,*, a Kelly J. Velasquez,a Dency J. Pacheco,a Jairo Quirogab and
Alejandro Ortízb
aGrupo de Investigación en Compuestos Heterocíclicos, Programa de Química,
Facultad de Ciencias Básicas, Universidad del Atlántico, Km 7 Antigua vía Puerto Colombia,
Barranquilla-Atlántico, Colombia
bGrupo de Investigación de Compuestos Heterocíclicos, Departamento de Química,
Universidad del Valle, A. A 25360 Cali, Colombia
Figure S1. 1H and 13C and DEPT-135 NMR spectra for compound 3a.
*e-mail: jorgetrilleras@mail.uniatlantico.edu.co

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Figure S2. 1H and 13C NMR spectra for compound 3b.

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Figure S3. 1H, 13C and DEPT-135 NMR spectra for compound 3c.

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Figure S4. 1H, 13C and DEPT-135 spectra for compound 3d.

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Figure S5. 1H, 13C and DEPT-135 spectra for compound 3e.

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Figure S6. 1H, 13C and DEPT-135 spectra for compound 3f.

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Figure S7. 1H, 13C and DEPT-135 spectra for compound 3g.

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Figure S8. 1H, 13C and DEPT-135 spectra for compound 3h.

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Figure S9. 1H, 13C and DEPT-135 spectra for compound 3i.

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Figure S10. 1H, 13C and DEPT-135 spectra for compound 3j.

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Figure S11. MS and IR spectra for Compound 3a.
Figure S12. MS and IR spectra for Compound 3b.

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Figure S13. MS and IR spectra for compound 3c.
Figure S14. MS and IR spectra for compound 3d.

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Figure S15. MS and IR spectra for compound 3e.
Figure S16. MS and IR spectra for compound 3f.

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Figure S17. MS and IR spectra for compound 3g.
Figure S18. MS and IR spectra for compound 3h.

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Figure S19. MS and IR spectra for compound 3i.
Figure S20. MS and IR spectra for compound 3j.