Synthesis, characterization, and antifungal activity of novel (Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-alkyl/aryl-sulfonamides derived from a Morita-Baylis-Hillman adduct

Article abstract of DOI:10.1016/j.molstruc.2014.03.011

A series of allyl sulfonamides prepared from the reaction of the Morita-Baylis-Hillman adduct 2-[hydroxy(phenyl)methyl]acrylonitrile with primary sulfonamides (RSO₂NH₂), where R = C₆H ₅ (1), 4-FC₆H₄ (2), 4-ClC₆H ₄ (3), 4-BrC₆H₄ (4), 4-NO₂C ₆H₄ (5), CH₃ (6), CH₃CH₂ (7), CH₃(CH₂)₃ (8), and CH₃(CH ₂)₇ (9), were characterized by IR, ¹H and ¹³C NMR spectroscopies, mass spectrometry and elemental analyses. BLYP/6-31G^* calculations suggested stereoselective reactions, resulting in the exclusive formation of the thermodynamically more stable Z-products. The Z-configuration of the products was confirmed by NOE difference spectroscopy and single crystal X-ray diffraction measurements. The allyl sulfonamides were active against Colletotrichum gloeosporioides, an important agent of anthracnose in plants.

Full text of DOI:10.1016/j.molstruc.2014.03.011

Journal of Molecular Structure 1067 (2014) 43–51
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, characterization, and antifungal activity of novel
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-alkyl/aryl-sulfonamides
derived from a Morita–Baylis–Hillman adduct
a
a
a
a
Eder C. Tavares a, , Mayura M.M. Rubinger , Carlos H.C. Zacchi , Simone A. Silva , Marcelo R.L. Oliveira ,
⇑
Silvana Guilardi b, Antônio F. de C. Alcântara c, Dorila Piló-Veloso c, Laércio Zambolim d
a Departamento de Química, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
b Instituto de Química, Universidade Federal de Uberlândia, 38408-100 Uberlândia, MG, Brazil
c Departamento de Química – ICEx, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil
d Departamento de Fitopatologia – CCA, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
ꢀ
Nine allyl sulfonamides derived from
a Morita–Baylis–Hillman adduct were
prepared.
ꢀ
The highly stereoselective reactions
yielded Z-isomers, as confirmed by
X-ray diffraction.
ꢀ
ꢀ
Their activity were tested against
Colletotrichum gloeosporioides.
Most of these allyl sulfonamides were
more active than the primary
sulfonamides.
a r t i c l e i n f o
a b s t r a c t
Article history:
A
series of allyl sulfonamides prepared from the reaction of the Morita–Baylis–Hillman adduct
Received 20 January 2014
Received in revised form 7 March 2014
Accepted 7 March 2014
2-[hydroxy(phenyl)methyl]acrylonitrile with primary sulfonamides (RSO2NH2), where R = C6H5 (1),
4-FAC6H4 (2), 4-ClAC6H4 (3), 4-BrAC6H4 (4), 4-NO2AC6H4 (5), CH3 (6), CH3CH2 (7), CH3(CH2)3 (8), and
CH3(CH2)7 (9), were characterized by IR, 1H and 13C NMR spectroscopies, mass spectrometry and elemen-
tal analyses. BLYP/6-31G* calculations suggested stereoselective reactions, resulting in the exclusive
formation of the thermodynamically more stable Z-products. The Z-configuration of the products was
confirmed by NOE difference spectroscopy and single crystal X-ray diffraction measurements. The allyl
sulfonamides were active against Colletotrichum gloeosporioides, an important agent of anthracnose in
plants.
Available online 17 March 2014
Keywords:
Morita–Baylis–Hillman adduct
Sulfonamides
Antifungal activity
Ó 2014 Elsevier B.V. All rights reserved.
Crystal structure
BLYP/6-31Gꢁ thermodynamic calculation
Introduction
The Morita–Baylis–Hillman (MBH) reactions are a versatile and
powerful carbon–carbon bond-forming method in organic
synthesis [1]. MBH reactions can provide in only one-step multi-
functionalized compounds which can be used as intermediates
⇑
Corresponding author. Present address: Instituto de Física e Química, Univer-
sidade Federal de Itajubá, 37500-903 Itajubá, MG, Brazil. Tel.: +55 3536291220; fax:
+55 3536291140.
E-mail address: eder@unifei.edu.br (E.C. Tavares).
http://dx.doi.org/10.1016/j.molstruc.2014.03.011
0022-2860/Ó 2014 Elsevier B.V. All rights reserved.

44
E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
for the preparation of biologically active substances [2], such as
sulfonamides. The synthesis of sulfonamides can be considered
as a milestone in chemotherapy, mainly due to their action against
bacteria. Several compounds bearing sulfonamide groups exhibit
other important biological properties, such as antitumor, antiglau-
coma and antifungal activities [3].
prepared under reflux by the reaction of the corresponding sulfo-
nyl chlorides with concentrated ammonia aqueous solution. The
Morita–Baylis–Hillman adduct was prepared from benzaldehyde,
as described in the literature [7].
Colletotrichum is a well-known genus of pathogenic fungi that
causes anthracnose in plants. This disease damages trees and food
crops, including cereals, legumes and fruits. The regular application
of fungicides is the most effective control of anthracnose, although
the reduction of effectiveness of commercial fungicides using stan-
dard spray schedules has been reported [4]. As a consequence, the
use of fungicides of different modes of actions to overcome fungal
resistance is an important practice [5]. The discovery of novel anti-
fungals is urgent to increase the structural variety of chemicals
available for field applications to control the fungal diseases.
In the present work, the synthetic approach described in the
literature [6] for the preparation of N-tosylaza–Baylis–Hillman
adducts was adapted and applied for the synthesis of nine allyl
sulfonamides with aromatic and aliphatic substituents attached
to the sulfonyl group (Scheme 1). These new compounds were
characterized by elemental analysis, infrared and NMR spectrosco-
pies and mass spectrometry. Additionally, the structures of the
General procedure for the syntheses of (Z)-N-(2-cyano-3-phenylprop-
2-en-1-yl)-alkyl/aryl-sulfonamides (1–9)
Concentrated sulfuric acid (54 lL) was added to a solution of
the MBH adduct (159 mg, 1.0 mmol) and the appropriate sulfon-
amide (1.5 mmol) in 1,2-dichloroethane (5 mL). After stirring
under reflux for 2–6 h, the reaction was completed (monitored
by TLC). Then, water (10 mL) was added and the product was ex-
tracted with ethyl acetate (3 ꢃ 10 mL). The organic phase was
dried over sodium sulfate and concentrated under reduced pres-
sure. The crude material was purified by column chromatography
on silica gel (hexane:ethyl acetate:dichloromethane 3:1:3). The
data obtained for the compounds 1–9 are as follows.
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-benzenesulfonamide (1):
yield 42%; white crystals; m.p. 98.9–99.1 °C; IR (ATR; m )
max/cmꢂ1
3267, 3061, 2214, 1624, 1493, 1446, 1325, 1215, 1156, 1091,
1068, 998, 930, 898, 867, 822, 751, 722, 687, 582, 552, 511, and
479; 1H NMR (CDCl3; 300 MHz) d3.94 (s; 2H; H1), 5.59 (bs; 1H;
NH), 7.06 (s; 1H; H3), 7.33–7.38 (m; 3H; H30, H40 and H50), 7.40–
7.50 (m; 3H; H6, H7 and H8), 7.56–7.59 (m; 2H; H5 and H9),
7.86–7.89 (m; 2H; H20 and H60); 13C-NMR (CDCl3; 75 MHz) d 47.2
(C1), 107.0 (C2), 117.5 (CN), 127.4 (C20 and C60), 129.0 (C30and
C50), 129.1 (C5 and C9), 129.4 (C6 and C8), 131.0 (C7), 132.9
(C40), 133.1 (C4), 140.4 (C10), 146.0 (C3); MS [m/z (%)] 298 (4)
[M]+Å, 157 (100), 155 (28), 140 (37), 115 (12), 77 (87), 51 (41). Anal.
Calcd. for C16H14N2O2S: C, 64.41%; H, 4.73%; N, 9.39%; Found: C,
64.17%; H, 4.71%; N, 9.32%.
compounds
1 and 3 were determined by X-ray diffraction
techniques. Effects of the allyl sulfonamides on the growth of
Colletotrichum gloeosporioides were evaluated in vitro.
Experimental
Methods and materials
Uncorrected melting points were determined with a MQAPF-
302 equipment. Microanalyses for C, H, and N were obtained from
a Perkin–Elmer 2400 CHN Elemental Analyzer. The IR spectra
(4000–500 cmꢂ1) were recorded on a FT-IR Varian 660 equipment
with GladiATR single reflection accessory. The 1H (300 MHz) and
13C (75 MHz) NMR spectra were recorded on a Varian spectropho-
tometer using CDCl3 or DMSO-d6 as solvents and TMS as internal
standard. COSY, HETCOR and NOEDIF experiments were performed
for structural characterization of the reaction products. GC/MS
experiments were performed using a Shimadzu QP5050-A mass
spectrometer, coupled to a Shimadzu GC17A gas chromatograph
(BD1 capillary column, 30 m), 70 eV. Methanesulfonamide,
benzenesulfonamide, 4-chlorobenzenesulfonamide, 4-nitroben-
zenesulfonamide, 4-fluorobenzenesulfonyl chloride, 4-bro-
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-4-fluorobenzenesulfona-
mide (2): yield 32%; white crystals; m.p. 115.7–116.8 °C; IR (ATR;
m
max/cmꢂ1) 3301, 3062, 2923, 2853, 2207, 1730, 1624, 1590,
1492, 1446, 1428, 1335, 1319, 1289, 1233, 1150, 1092, 1071,
1009, 935, 907, 882, 834, 756, 709, 699, 685, 660, 623, 592, 571,
543, 503, 445; 1H NMR (CDCl3; 300 MHz) d 3.97 (s; 2H; H1), 5.62
(bs; 1H; NH), 7.07–7.15 (m; 3H; H3, H30 and H50), 7.35–7.42 (m;
3H; H6, H7 and H8), 7.58–7.62 (m; 2H; H5 and H9), 7.87–7.93
(m; 2H; H20 and H60); 13C NMR (CDCl3; 75 MHz) d 47.4 (C1),
106.4 (C2), 116.7 (d; C-FJ = 22.5 Hz; C30 and C50), 117.5 (CN),
129.1 (C5 and C9), 129.2 (C6 and C8), 130.2 (d; C-FJ = 9.7 Hz; C20
C-F
and C60), 131.3 (C7), 132.6 (C4), 136.3 (d; J = 3.0 Hz; C10), 146.3
mobenzenesulfonyl
chloride,
methanesulfonyl
chloride,
(C3), 165.4 (d; C-FJ = 254.2 Hz; C40); MS [m/z (%)] 316 (5) [M]+Å,
157 (100), 155 (38), 140 (35), 130 (9), 115 (10), 95 (39), 51 (15),
44 (25). Anal. Calcd. for C16H13FN2O2S: C, 60.75%; H, 4.14%; N,
8.86%; Found: C, 60.31%; H, 4.22%; N, 8.77%.
ethanesulfonylchloride, butanesulfonyl chloride, and octanesulfo-
nyl chloride were purchased from Aldrich. The R-sulfonamides
(R = 4-F-phenyl, 4-Br-phenyl, ethyl, n-butyl, and n-octyl) were
Scheme 1. Syntheses and NMR numbering.

E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
45
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-4-chlorobenzenesulfona-
[M]+Å, 235 (2), 219 (1), 157 (100), 155 (52), 140 (11), 130 (18),
115 (20), 102 (14), 77 (27), 63 (6), 51 (18), 44 (30), 40 (44). Anal.
Calcd. for C12H14N2O2S: C, 57.58%; H, 5.64%; N, 11.19%; Found: C,
56.40%; H, 5.85%; N, 11.28%.
mide (3): yield 39%; white crystals; m.p. 128.2–128.4 °C; IR (ATR;
m
max/cmꢂ1) 3263, 2925, 2854, 2210, 1627, 1586, 1493, 1474,
1447, 1427, 1394, 1355, 1322, 1277, 1214, 1178, 1155, 1090,
1046, 1011, 932, 908, 870, 834, 825, 704, 629, 505, 481; 1H NMR
(CDCl3; 300 MHz) d 4.00 (s; 2H; H1), 5.11 (bs; 1H; NH), 7.04 (s;
1H; H3), 7.40–7.45 (m; 5H; H6, H7, H8, H30 and H50), 7.58–7.61
(m; 2H; H5 and H9), 7.79–7.83 (m; 2H; H20 and H60); 13C NMR
(CDCl3; 75 MHz) d 46.6 (C1), 106.4 (C2), 117.3 (CN), 128.9 (C20
and C60), 129.1 (C30 and C50), 129.2 (C5 and C9), 129.8 (C6 and
C8), 131.4 (C7), 132.5 (C4), 138.9 (C40), 139.9 (C10), 146.3 (C3);
MS [m/z (%)] 332 (3) [M]+Å, 157 (100), 155 (39), 140 (33), 111
(33), 75 (24), 51 (13). Anal. Calcd. for C16H13ClN2O2S: C, 57.7%; H,
3.94%; N, 8.42%; Found: C, 57.71%; H, 4.09%; N, 8.38%.
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-butanesulfonamide (8):
yield 54%; white solid; m.p. 99.2–99.7 °C; IR (ATR;
m )
max/cmꢂ1
3285, 3056, 2961, 2934, 2873, 2217, 1630, 1497, 1450, 1412,
1315, 1299, 1276, 1143, 1076, 873. 1H NMR (CDCl3; 300 MHz) d
0.92 (t; 3H; J4 ,3 = 9 Hz; H40), 1.43 (sex; 2H; J3 ,2 = J3 ,4 = 9 Hz;
H30), 1.78–1.88 (m; 2H; H20), 3.04–3.11 (m; 2H; H10), 4.08 (dd;
2H; J1,NH = 6 Hz, J1,3 = 3 Hz; H1), 5.18 (t; 1H; JNH,1 = 6 Hz; NH),
7.20 (bs; 1H; H3), 7.43–7.45 (m; 3H; H6, H7 and H8), 7.75–7.78
0
0
0
0
0
0
13
(m; 2H; H5 and H9); C NMR (CDCl3; 75 MHz) d 13.8 (C40), 21.7
(C30), 25.8 (C20), 47.4 (C1), 54.4 (C10), 107.5 (C2), 117.9 (CN),
129.3 (C5, C6, C8 and C9), 131.3 (C7), 132.8 (C4), 146.2 (C3); MS
[m/z (%)] 278 (2) [M]+Å, 252 (1), 157 (100), 140 (51), 130 (13),
115 (15), 102 (8), 89 (3), 77 (14), 57 (20), 44 (8), 41 (36). Anal.
Calcd. for C14H18N2O2S: C, 60.41%; H, 6.52%; N, 10.06%; Found: C,
59.88%; H, 6.58%; N, 10.01%.
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-4-bromobenzenesulf-
onamide (4): yield 35%; white crystals; m.p. 145.0–145.9 °C; IR
(ATR;
m
max/cmꢂ1) 3234, 2222, 1574, 1492, 1470, 1438, 1345,
1323, 1277, 1160, 1090, 1068, 1007, 992, 933, 903, 817, 776,
735, 720, 698, 686, 629, 604, 570, 547, 514, 481, 470, 430, 415;
1H NMR (DMSO-d6; 300 MHz) d 3.83 (d; 2H; J1,NH = 6 Hz; H1),
7.27 (s; 1H; H3), 7.42–7.45 (m; 3H, H6, H7 and H8), 7.60–7.63
(m; 2H; H5 and H9), 7.72–7.81 (m; 4H; H20, H60, H30 and H50),
8.47 (t; 1H; JNH,1 = 6.0 Hz; NH); 13C NMR (DMSO-d6; 75 MHz) d
47.0 (C1), 108.4 (C2), 118.2 (CN), 127.1 (C40), 129.2 (C5 and C9),
129.3 (C20 and C60), 129.6 (C6 and C8), 131.2 (C7), 133.0 (C30
and C50), 133.5 (C4), 140.6 (C10), 146.0 (C3); MS [m/z (%)] 378
(5) [M]+Å, 221 (8), 157 (100), 155 (63), 140 (43), 130 (13), 115
(14), 77 (18), 51 (15). Anal. Calcd. for C16H13BrN2O2S: C, 50.94%;
H, 3.47%; N, 7.43%; Found: C, 50.93%; H, 3.58%; N, 7.31%.
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-octanesulfonamide (9):
yield 45%; white solid; m.p. 98.1–98.3 °C; IR (ATR;
m )
max/cmꢂ1
3266, 3057, 2962, 2928, 2955, 2215, 1626, 1450, 1417, 1317,
1265, 1213, 1139, 1076, 874, 734, 691; 1H NMR (CDCl3;
300 MHz) d 0.87 (t; 3H; J8 ,7 = 9 Hz; H80), 1.24–1.41 (m; 10H; H30,
H40, H50, H60 and H70), 1.76–1.89 (m; 2H; H20), 3.04–3.10 (m; 2H;
H10), 4.09 (dd; 2H; J1,NH = 6 Hz, J1,3 = 3 Hz; H1), 5.11 (t; 1H;
JNH,1 = 6 Hz; NH), 7.20 (bs; 1H; H3), 7.43–7.45 (m; 3H; H6, H7
and H8), 7.75–7.78 (m; 2H; H5 and H9); 13C NMR (CDCl3;
75 MHz) d 14.3 (C80), 22.8 (C70), 23.9 (C60), 28.4 (C50), 29.2 (C40),
29.3 (C30), 31.9 (C20), 47.4 (C1), 54.7 (C10), 107.5 (C2), 117.9 (CN),
129.2 (C5, C6, C8 and C9), 131.3 (C7), 132.7 (C4), 146.2 (C3); MS
[m/z (%)] 334 (1) [M]+Å, 281 (1), 252 (2), 235 (1), 207 (3), 157
(100), 140 (28), 130 (8), 115 (13), 96 (1), 77 (7), 57 (15), 44 (33)
and 40 (11). Anal. Calcd. for C18H26N2O2S: C, 64.64%; H, 7.84%; N,
8.37%; Found: C, 64.42%; H, 7.94%; N, 8.39%.
0
0
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-4-nitrobenzenesulfona-
mide (5): yield 40%; white crystals; m.p. 205.4–206.0 °C; IR (ATR;
m
max/cmꢂ1) 3289, 3108, 2840, 2354, 2208, 1624, 1606, 1523,
1419, 1349, 1307, 1158, 1109, 1079, 736. 1H NMR (DMSO-d6;
300 MHz) d 3.88 (s; 2H; H1), 7.31(s; 1H; H3), 7.43–7.45 (m; 3H;
H6; H7 and H8), 7.60–7.63 (m; 2H; H5 and H9), 8.06 (m; 2H; H20
and H60), 8.37 (m; 2H; H30 and H50); 13C NMR (DMSO-d6;
75 MHz) d 46.9 (C1), 108.1 (C2), 118.2 (CN), 125.3 (C20 and C60),
128.9 (C30 and C50), 129.2 (C5 and C9), 129.6 (C6 and C8), 131.4
(C7), 133.4 (C4), 146.2 (C3), 146.8 (C10), 150.2 (C40); MS [m/z (%)]
343 (4) [M]+Å, 186 (4), 157 (100), 140 (24), 130 (8), 115 (13), 102
(6), 77 (14), 51 (12), 44 (16), 30 (15). Anal. Calcd. for C16H13N3O4S:
C, 55.97%; H, 3.82%; N, 12.24%; Found: C, 56.03%; H, 3.76%; N,
12.30%.
X-ray crystallography
Suitable single crystals of compounds 1 and 3 were obtained
from their solutions in a chloroform and petroleum ether mixture.
Room temperature diffraction intensities for compounds 1 and 3
were measured on an Enraf–Nonius Kappa-CCD diffractometer
using graphite-monochromated MoKa radiation (0.71073 Å). Data
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-methanesulfonamide
(6): Yield 69%; white solid; m.p. 115.8–116.2 °C; IR (ATR; mmax
collections were made using the COLLECT program [8] and the final
unit cell parameters were derived from all reflections. Integration,
reduction and scaling of X-ray data were performed with the HKL
Denzo–Scalepack programs [9]. The structures were solved by di-
rect methods with SHELXS-97 [10] and refined by full-matrix least
squares method on F2 using the SHELXL-97 [10], with anisotropic
atomic displacement parameters for non-hydrogen atoms. All
hydrogen atoms were stereochemically positioned and refined
with the riding model. The WinGX [11] program was used to pre-
pare the material for publication. Structural analysis and figures
were made using the MERCURY [12] and ORTEP-3 [13] programs.
The crystal data and results of the analyses are listed in Table 1.
/
cmꢂ1) 3251, 3025, 2932, 2213, 1628, 1494, 1447, 1410, 1309,
1141, 1073, 1061, 969. 1H NMR (CDCl3; 300 MHz) d 3.05 (s; 3H;
H10), 4.11(dd; 2H; J1,NH = 6.0 Hz; J1,3 = 3 Hz; H1), 5.28 (t; 1H,
JNH,1 = 6.0 Hz; NH), 7.21 (bs; 1H; H3), 7.43–7.47 (m; 3H; H6, H7
and H8), 7.75–7.79 (m; 2H; H5 and H9); 13C NMR (CDCl3;
75 MHz) d 42.3 (C10), 47.5 (C1), 107.3 (C2), 117.9 (CN), 129.3 (C5,
C6, C8 and C9), 131.4 (C7), 132.7 (C4), 146.3 (C3); MS [m/z (%)]
236 (5) [M]+Å, 219 (1), 157 (100), 155 (95), 140 (73), 130 (20),
115 (24), 102 (18), 77 (32), 63 (12), 51 (24), 44 (47), 40 (81). Anal.
Calcd. for C11H12N2O2S: C, 55.91%; H, 5.12%; N, 11.85%; Found: C,
55.91%; H, 5.15%; N, 11.93%.
(Z)-N-(2-cyano-3-phenylprop-2-en-1-yl)-ethanesulfonamide (7):
yield 65%; white solid; m.p. 93.7–94.5 °C; IR (ATR;
Computational calculations
m )
max/cmꢂ1
3259, 2980, 2944, 2215, 2159, 1626, 1574, 1453, 1420, 1383,
LogP of the compounds 1–9 and of the parent primary sulfona-
mides were calculated using the program ACD/logP.
1307, 1242, 1139, 1077, 1052, 871; 1H NMR (CDCl3; 300 MHz) d
1.41 (t; 3H; J2 ,1 = 9 Hz; H20), 3.11 (q; 2H; J1 ,2 = 9 Hz; H10), 4.08
(dd; 2H; J1,NH = 6 Hz, J1,3 = 3 Hz; H1), 5.26 (t; 1H; JNH,1 = 6 Hz;
NH), 7.20 (bs; 1H; H3), 7.43–7.45 (m; 3H; H6, H7 and H8), 7.75–
Theoretical studies were carried out using the Gaussian 09
software package [14]. The geometries obtained from PM3 semi-
empirical calculations were used as initial models in geometry
optimizations employing DFT calculations with the Pople’s split
valence basis set 6-31G*. BLYP exchange–correlation functional
was used in DFT calculations. The optimized geometries were
0
0
0
0
13
7.78 (m; 2H; H5 and H9); C NMR (CDCl3; 75 MHz) d 8.5 (C20),
47.4 (C1), 49.0 (C10), 107.5 (C2), 117.9 (CN), 129.3 (C5, C6, C8 and
C9), 131.3 (C7), 132.8 (C4), 146.2 (C3); MS [m/z (%)] 250 (5)

46
E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
Table 1
MeSO3H (1.2 mL, ca. 18 mmol) [6]. Nevertheless, the use of this
catalyst led to very low yields of the allyl sulfonamides (up to
30%), due to the hydrolysis of the nitrile group and also to the reac-
tion of the MBH with the methanesulfonate nucleophile, as indi-
cated by CG–MS. Thus, the reduction of the amount of MeSO3H
improved the yields, but better results (up to 69%) were achieved
Crystal data and details of diffraction experiments for compounds 1 and 3.
Compound
1
3
Empirical formula
C
16H14N2O2S
C16H13N2O2SCl
332.79
293(2)
Formula weight (g molꢂ1
Temperature (K)
)
298.35
293(2)
Crystal system/space group Monoclinic/P21/a
Triclinic/P-1
using diluted H2SO4 (54 lL, ca. 1 lmol) as catalyst. However, the
Unit cell dimensions
hydrolysis products were still observed in some extent by CG–
MS, together with the formation of very small amounts of the
disubstituted sulfonamides. The formation of E-isomers was not
observed.
a (Å)
b (Å)
C (Å)
7.6794(2)
22.9914(4)
8.4481(2)
90
94.308(1)
90
1487.38(6), 4
1.332
0.223
7.1657(3)
10.2707(5)
11.6729(6)
92.165(3)
104.699(3)
107.685(3)
785.53(6), 2
1.407
a
(°)
Compounds 1–9 were structurally characterized by CG–MS,
elemental analysis, and by infrared and NMR spectroscopies. Spec-
troscopic data obtained for 6 are in accordance with the literature
[6]. However, the literature reports that 6 melts at the range of
103–104 °C with decomposition, while we observed a clear melt-
ing point at 115.8–116.2 °C, with no evidence of decomposition.
The molecular ion peaks were observed in the mass spectra of
all allyl sulfonamides, which also exhibited the base peak at m/z
157 due to the common fragment [C10H9N2]+. Their molecular for-
mulae and purity were confirmed by elemental analyses of C, H
and N.
b (°)
c
(°)
Volume (Å3), Z
Calculated density (g/cm3)
Absorption coefficient
0.384
(mmꢂ1
F(000)
)
624
344
Crystal size (mm)
h range for data collection
(°)
Limiting indices
Reflections collected/
unique
0.289 ꢃ 0.265 ꢃ 0.232 0.653 ꢃ 0.081 ꢃ 0.035
3.00–26.74
2.94–27.49
ꢂ9, 9; ꢂ28, 29; 0, 10
ꢂ9, 8; ꢂ13, 13; 0, 14
15101/ 3131
7309/3521
R (int)
0.0320
2152
0.1406
1807
The infrared spectra of 1–9 showed bands at 3301–3234 and
Observed reflections [I > 2
(I)]
Parameters refined
Goodness-of-fit on F2
Final R indices [I > 2
r
2222–2207 cmꢂ1
,
assigned to the NAH and CBN stretching
frequencies, respectively. The presence of the SO2 group was
confirmed by the SO2as and SO2sym bands at 1325–1307 and
1214–1139 cmꢂ1, respectively. The expected bands due to
C@C
were observed at 1630–1574 cmꢂ1
190
1.060
199
0.915
m
m
r
(I)]
R = 0.0537,
wR = 0.1585
R = 0.0771,
wR = 0.1723
0.340; ꢂ0.406
R = 0.0561,
wR = 0.1325
R = 0.1226,
wR = 0.1537
0.421; ꢂ0.331
m
.
R indices (all data)
In the 1H NMR spectrum of the MBH adduct, two signals are ob-
served at d 6.02 and 6.10 which are assigned to the sp2-CH2 methy-
lenic hydrogens H1 and H3 [7]. In the NMR spectra of 1–9 these
signals were substituted by one signal at d 4 (H1) characteristic
for the sp3-CH2-N moiety, while the signal of H3, now an sp2-CH
hydrogen atom, was shifted to d 7.1–7.3. Further, the H1 signal ap-
peared as a singlet in the spectra of 1–3 and 5, and as a doublet in
the spectrum of 4, or a double–doublet in the spectra of 6–9. These
multiplicities are due to coupling constants of ca. 6 Hz with the
NAH hydrogen atom (observed in the spectra of compounds 4
and 6–9), and of ca. 3 Hz with H3 (observed in the spectra of com-
pounds 6–9). Coherently, the NH signal appeared as a triplet (J ca.
6 Hz) in the range of d 5.1–5.6 in the spectra of 6–9 (CDCl3) and at d
8.5 in the spectrum of 4 (DMSO-d6).
Max.; min. in
(e Aꢂ3
Dq map
)
1=2
wðjF2o j ꢂ jF2c jÞ2=
R
wjF2oj ꢄ
.
2
R1
=
R
(||Fo| ꢂ |Fc||)/
R
|Fo|; wR2 ¼ ½
R
characterized as true minima on the potential energy surface (PES)
when all harmonic frequencies were real. The electronic-nuclear
energy (E) of the optimized geometries was given in atomic unit
(Hartree). These theoretical methodologies have been efficiently
employed in the study of different organic compounds [15–20].
Biological assay
The antifungal activity of 1–9 was evaluated by the Poisoned
food technique [21] against C. gloeosporioides. Discs of mycelia of
the fungus (diameter of 6 mm) were placed on the center of Petri
dishes containing 6 mL of the culture medium (PDA) homoge-
neously mixed with the tested compounds at the concentration
of 1.5 mM, dimethylsulfoxide (1% v/v), and the antibiotic chloram-
phenicol (Pfizer) (0.5% v/v). Each treatment consisted of four repe-
titions and the dishes were incubated at 25 °C for 9 days. The
diameter of the fungus colony was measured with the aid of a cal-
iper every 24 h from the second day of incubation. Effects of the
parent primary sulfonamides were also tested, under the same
conditions. The control (negative check treatment, four repetitions)
was prepared with PDA, dimethylsulfoxide and chloramphenicol.
Results were analyzed using Tukey’s test at P = 0.05.
The H1 (ca. d 4) and H3 (d 7.0–7.3) signals were correlated to
the 13C NMR signals, respectively at ca. d 47 (in the CAC single
bonds region) and at d 146 (in the C@C region), in the HETCOR
experiments for compounds 1–9.
As compounds 6–9 have only the aromatic ring from the MBH
adduct, the remaining signals observed in the region from 7 to
8 ppm in their 1H NMR spectra were easily assigned to the hydro-
gen atoms H6, H7, H8 (d 7.4–7.5) and H5, H9 (d 7.7–7.8). This pat-
tern could also be recognized in the spectra of compounds 1–5, as
exemplified in Fig. 1, what helped the identification of the hydro-
gen signals of the aromatic sulfonamide groups.
From the spectra of the sulfonamides 6–9 it was also possible to
recognize the signals of the aromatic carbons C4 (ca. d 133) and C7
(ca. d 131) in all spectra. The signals of C5, C6, C8 and C9 were
superposed at ca. d 129 in the spectra of 6–9. In the spectra of 1–
5 the region around d 129 was complicated by other signals from
the sulfonamides aromatic R groups. In the spectrum of compound
2 (Fig. 2), the assignments of these signals were straightforward
due to the coupling constants of the carbon and fluorine atoms,
allowing the identification of the signals of C40 (d 165.4,
J = 254.2 Hz), C30 and C50 (d 116.7, J = 22 Hz), C20 and C60 (d 130.2,
J = 9.7 Hz) and C10 (d 136.3, J = 3 Hz).
Results and discussion
Synthesis and characterization
Compounds 1–9 were prepared as shown in Scheme 1, which
also displays the numbering used for the NMR assignments. Exper-
imental data for compound 6 have been previously published [6].
The methodology initially employed was based on the procedure
described for the preparation of compound 6, in the presence of
The HETCOR contour maps confirmed the assignments of the
NMR signals in the aromatic region. For example, for compound

E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
47
Fig. 1. Fragments of the 1H NMR spectra of compounds 5 and 7 showing the region of the aromatic hydrogen signals.
Fig. 2. Fragment of the 13C NMR spectrum of compound 2 showing the region of the aromatic carbon signals.
4 (R = C6H4Br) the signal at d 129.2 (C5 and C9) is correlated to the
X-ray crystallography
hydrogen signal at d 7.60–7.63 (H5 and H9) while the slightly
lower field signal at d 129.6 (C6 and C8) is correlated to the multi-
plet at d 7.42–7.45 (H7, H6 and H8), which is also correlated to the
signal of C7 (d 131.2). The signal of C20 and C60 (d 129.3) could be
identified due to its correlation with the signal of the hydrogen
atoms of the sulfonamide group (d 7.72–7.81). In turn, this hydro-
gen signal is also correlated to the signal of C30 and C50 (d 133.0).
The molecular structures of 1 and 3 with the atom numbering
scheme are given in Figs. 3 and 4, respectively. Some important
bond lengths, bond angles and torsion angles are listed in Table 2.
Compound
1 crystallizes in the monoclinic system while
compound 3 crystallizes in the triclinic system (Table 1). Both
compounds exhibit Z-configuration and all bonds and angles are
similar and within normally expected ranges.
The
Z configuration of the allyl sulfonamides could be
determined by NMR, through the irradiation of the H3 signal in
NOE difference spectroscopy, producing the enhancement of the
H1 signal. This stereochemistry assignment was unambiguously
confirmed by X-ray diffraction analysis after the isolation of the
allyl sulfonamides 1 and 3 as single crystals from chloroform–
petroleum ether solutions.
The sulfur atoms in both molecules have a distorted tetrahedral
coordination, similar to other reported sulfonamide structures
[22–24], probably due to non-bonded intramolecular distances.
The contact distances O1AO2, O1AN1, O2AN1, O1AC10 and
O2AC10 are in the range of 2.4–2.6 Å, resulting in structures with
less steric interferences [22]. The S@O bond lengths present

48
E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
ring (C10AC60) for the compounds 1 and 3, respectively. In
compound 3, the chlorine atom is in the same plane defined by
the benzene ring (the root mean square deviation to the fitted
atoms is 0.016(4) Å). The substitution of one hydrogen atom at
the 4-position of the benzene ring by chlorine atom alters the
molecular conformation (torsion angles in Table 2) and the inter-
molecular architecture displayed by the compound 1.
Only one intramolecular C60AH60ꢅ ꢅ ꢅO2 interaction is observed
in the structure of 1, while in 3, two intramolecular interactions
(C60AH60ꢅ ꢅ ꢅO2 and C1AH1aꢅ ꢅ ꢅO2) are observed. In the crystal
packing, both compounds form inversion-related dimmers through
N1AH1ꢅ ꢅ ꢅN2 hydrogen bond, resulting in a twelve membered ring
motif R22 (12) (Table 3). The dimeric unit represents the basic
supramolecular element of the crystal structures. In 1, these di-
mers are linked by C3AH3ꢅ ꢅ ꢅO2 interactions in the plane ab and
C5AH5ꢅ ꢅ ꢅ
P contacts (the centroid acceptor P correspond to the
phenyl ring with donor–acceptor distance of 3.634(2) Å) forming
a three-dimensional supramolecular framework. In 3, these dimers
are linked by C3AH3ꢅ ꢅ ꢅO2 interactions to form layers in the plane
ac and the adjacent layers were stacked via van der Waals interac-
tions (Figs. 5 and 6). These intramolecular interactions led to the
pronounced U shape conformation observed for the molecules 1
and 3 (Figs. 3 and 4).
Fig. 3. An ORTEP-3 view of 1, showing 30% probability displacement ellipsoids.
Computational calculations
The stereochemistry of the allyl sulfonamides was investigated
using theoretical methodology. Scheme 2 shows one possible
Table 2
Selected bond lengths (Å), bond angles (°) and torsion angles (°) for 1 and 3.
Compound
1
3
Bond lengths
SAO(1)
SAO(2)
SAN(1)
SAC(10)
N(1)AC(1)
N(2)AC(10)
C(1)AC(2)
C(2)AC(3)
C(2)AC(10)
C(3)AC(4)
C(40)ACl
1.4203(18)
1.4287(16)
1.611(2)
1.760(2)
1.469(3)
1.142(3)
1.515(4)
1.340(3)
1.430(3)
1.461(3)
–
1.4292(19)
1.4280(19)
1.607(2)
1.764(3)
1.460(3)
1.138(3)
1.514(4)
1.332(4)
1.433(4)
1.456(4)
1.739(3)
Bond angles
O(1)ASAO(2)
O(1)ASAN(1)
O(2)ASAN(1)
O(1)ASAC(10)
O(2)ASAC(10)
N(1)ASAC(10)
SAN(1)AC(1)
C(1)AC(2)AC(10)
C(2)AC(10)AN(2)
C(10)AC(2)AC(3)
C(1)AC(2)AC(3)
N(1)AC(1)AC(2)
C(2)AC(3)AC(4)
120.07(11)
106.22(11)
106.61(11)
107.16(11)
108.63(10)
107.57(9)
121.82(16)
114.3(2)
174.9(3)
123.0(2)
122.5(2)
115.1(2)
120.25(12)
106.16(12)
107.18(12)
107.30(12)
107.56(13)
107.87(11)
121.06(18)
114.5(2)
175.2(3)
122.9(3)
122.6(3)
115.2(2)
Fig. 4. An ORTEP-3 view of 3, showing 30% probability displacement ellipsoids.
shorter values than those in N,N0-polymethylenebis-sulfonamides
while the SAN and SAC bond lengths have similar values [23].
The SAN and SAC distances are shorter than the corresponding
single-bond distances. These bond shortenings have been attrib-
129.8(2)
131.2(3)
Torsion angles
O(1)ASAN(1)AC(1)
O(2)ASAN(1)AC(1)
C(10)ASAN(1)AC(1)
O(1)ASAC(10)AC(20)
O(1)ASAC(10)AC(60)
O(2)ASAC(10)AC(20)
O(2)ASAC(10)AC(60)
SAN(1)AC(1)AC(2)
N(1)AC(1)AC(2)AC(3)
N(1)AC(1)AC(2)AC(10)
C(2)AC(3)AC(4)AC(5)
C(2)AC(3)AC(4)AC(9)
165.17(17)
36.03(19)
ꢂ80.34(19)
35.4(2)
ꢂ147.04(17)
166.47(17)
ꢂ15.9(2)
63.5(3)
169.87(19)
40.2(2)
uted to dp–pp interactions between these atoms.
The C10AN2 bond length of 1.142(3) Å in 1, and 1.138(3) Å in 3
is consistent with a triple bond, while the C1AN1 bond length of
1.460(3) Å in both compounds fits in the value for a single bond.
The angle C1AN1AS are 121.9(2)° and 121.1(2)°, respectively in
1 and 3, which are consistent with the partial sp2 hybrid character
of the N1 atom. The C2AC3 distance confirms the double bond
character.
ꢂ75.4(2)
51.0(2)
ꢂ128.9(2)
ꢂ178.3(2)
1.8(2)
67.1(3)
ꢂ116.4(3)
ꢂ112.5(3)
58.2(3)
67.0(3)
ꢂ149.7(2)
28.3(4)
160.1(3)
ꢂ21.6(5)
The mean plane of the phenyl ring (C4AC9) forms dihedral an-
gles of 47.06(7)° and 20.83(8)° with the mean plane of the benzene

E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
49
Table 3
Hydrogen-bond geometry (Å, °) in the crystal structures of 1 and 3.
DAHꢅ ꢅ ꢅA
d(DAH)
d(Hꢅ ꢅ ꢅA)
d(Dꢅ ꢅ ꢅA)
<(DHꢅ ꢅ ꢅA)
Compound 1
C(60)AH(60)ꢅ ꢅ ꢅO(2)
N(1)AH(1)ꢅ ꢅ ꢅN(2)i
C(3)AH(3)ꢅ ꢅ ꢅO(2)ii
C(5)AH(5)ꢅ ꢅ ꢅCgiii
0.93
0.86
0.93
0.93
2.58
2.38
2.57
2.95
2.940(3)
3.033(3)
3.424(3)
3.633(2)
103.6
133.5
153.3
131
Compound 3
C(60)AH(60)ꢅ ꢅ ꢅO(2)
C(1)AH(1a)ꢅ ꢅ ꢅO(2)
N(1)AH(1)ꢅ ꢅ ꢅN(2)iv
C(3)AH(3)ꢅ ꢅ ꢅO(2)v
0.93
0.97
0.86
0.93
2.52
2.60
2.30
2.68
2.894(4)
2.926(3)
2.980(3)
3.405(3)
104.4
99.9
136.0
134.9
Symmetry codes: (i) 1 ꢂ x, ꢂy, ꢂz; (ii) ½ + x, ½ ꢂ y, z; (iii) ꢂ½ + x, ½ ꢂ y, z; (iv) 2 ꢂ x,
ꢂy, 2 ꢂ z; (v) 1 ꢂ x, ꢂy, 1 ꢂ z. Cg is the centroid of the C4AC9 ring.
mechanism for the formation of compounds 1–9 from the MBH
adduct and the corresponding sulfonamides. The reaction can
occur via intermediates A or B, providing the isomeric Z or E
products, respectively.
BLYP/6-31Gꢁ geometry optimizations were carried out for the
corresponding intermediates A and B considering the formation
of compounds 1–9 via the proposed mechanism shown in
Scheme 2. The energy values obtained for the intermediates A
are lower than those obtained for the intermediates B (DE = 2.25,
1.91, 1.91, 1.91, 1.86, 1.97, 1.89, 1.94, and 1.93 kcal/mol, respec-
tively for the formation of 1–9). Although the energy differences
between the intermediates A and B are small, these theoretical
results suggest that the formation of the Z-isomers are energeti-
cally favorable. Similar results were obtained when the Z and E
allyl sulfonamides 1–9 were compared. The Z-isomers of 1 to 9
showed lower energy values in relation to the corresponding E-iso-
Fig. 5. Packing diagram of 1, in the ab plane.
mers (DE = 1.17, 1.62, 1.26, 1.26, 1.56, 2.72, 1.60, 0.86, and
1.66 kcal/mol, respectively).
Thus, the BLYP/6-31Gꢁ geometry optimization calculations
suggested that the lower energy of the intermediates A (Scheme 2)
contributes to the formation of the corresponding Z-isomers.
Moreover, as expected, the Z-isomers are the thermodynamically
favored products.
ity in this case could be reasoned considering the greater steric
hindrance of the transition state leading to the isomer E [1b]. Thus,
via an SN20 mechanism, the isomer Z would still be the main
product.
Although the aprotic solvent of low dielectric constant (1,2-
dichloroethane) would not favor the formation of carbocations, a
possible variation of the mechanism shown in Scheme 2 could
involve the elimination of water, forming a benzylic cation, from
which the formation of the most stable Z-product should be
favored.
Antifungal assay
The synthesized allyl sulfonamides (1–9) were tested in vitro for
their growth inhibitory activity against C. gloeosporioides using the
Poisoned Food method [21]. The biological tests included the
primary parent sulfonamides for comparison. The bioassay results
are summarized in Table 4.
The reaction could also occur via SN20, as proposed by Basavaiah
[1]. In this mechanism, the addition of the sulfonamide and the
elimination of water are simultaneous. The reaction stereoselectiv-
No straightforward relation between their structures and the
biological activities was observed. Nevertheless, some general
Fig. 6. Packing diagram of 3.

50
E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
Scheme 2. A possible mechanism for the formation of Z and E isomers from the MBH adduct and sulfonamides.
provided the second best result. The literature suggests that the
Table 4
nitro group, especially in the para position on the aromatic ring
with respect to the sulfonyl group, can be reduced in the biological
medium to form the oxime, and the amine afterwards [26]. Thus,
the nitro group could act as an additional active site for the
inhibition of the fungal growth.
Percentage of mycelial growth inhibition of C. gloesporoides after 9 days of incubation
at 25 °C in the presence of allyl sulfonamides 1–9 and the corresponding primary
sulfonamides containing the same R groups, and the logP of the tested compounds.
R
Sulfonamides
Allyl sulfonamides 1–9
Conclusion
Inhibition %
20 c
logP
Inhibition %
48 i
logP
0.33
3.85
4.17
4.80
4.89
4.05
Nine allyl sulfonamides (1–9) were synthesized from the
reaction of a Morita–Baylis–Hillman adduct with primary sulfona-
mides. All compounds were characterized by IR, 1H NMR, 13C NMR,
MS and elemental analysis techniques. The allyl sulfonamide 6 is
already described but its characterization by elemental analysis
and mass spectrometry is reported here for the first time. All com-
pounds exhibited the Z configuration, confirmed by NOE difference
spectroscopy and by single crystal X-ray diffraction measurements.
Theoretical calculations confirmed that the formation of the Z iso-
mers are thermodynamically favored when compared to the E iso-
mers. The results of X-ray diffraction analysis show that the
NAHꢅ ꢅ ꢅN hydrogen bond is the main force stabilizing the pairs of
centrosymmetric dimers present in the compounds 1 and 3
crystals. These dimers interact through CAHꢅ ꢅ ꢅO contacts forming
layers in the plane ab for compound 1 and in the plane ac for
compound 3. The three-dimensional supramolecular framework
15 b
21 c
0.64
0.84
1.36
0.65
23 c
22 c
15 b
43 h
32 ef
31 de
–CH3
–CH2CH3
–CH2CH2CH2CH3
–CH2CH2CH2CH2
CH2CH2CH2CH3
0 a
0 a
0 a
39 c
ꢂ1.29
ꢂ0.76
0.31
34 f
38 g
42 h
22 d
1.93
2.46
3.52
5.65
2.43
Inhibition % = (dc ꢂ dt)/dc ꢃ 100; where dc = average diameter (in mm) of fungal
colony in control, dt = average diameter (in mm) of fungal colony in the treatment.
Values followed by different letters are significantly different by the Tukey test at
5% probability.
is stabilized by the intermolecular CAHꢅ ꢅ ꢅ
P contacts in 1 and by
van der Waals forces in 3. The compounds 1–9 were active against
C. gloeosporioides. Compounds 1, 5 and 8 showed the best results,
and were considerably more active than the parent primary sulfon-
amides. Thus the biological activity of the allyl sulfonamides are
worth of further investigation, for their potential application as
agrochemicals.
features can be clearly pointed out. Except for compounds 4 and 9,
the allyl sulfonamides were more active than the parent primary
sulfonamides. Among the allyl sulfonamides with aliphatic
moieties, it was observed an increase in the activity with the
increase of the chain length from 1 to 4 carbon atoms. However,
the replacement of the n-butyl group (compound 8) by the much
longer n-octyl group (compound 9) had a detrimental effect on
the antifungal activity. These facts indicated that the lipophilicity
of the compounds is an important factor, showing lower and upper
limits.
The partition coefficient (logP) is related to the lipophilicity of a
substance and can be an useful information for the prediction of
the permeability of the cell membranes to the agrochemicals
[25]. Thus, logP values were calculated and are displayed in Table 4.
These results indicated that the higher activity of the 4-bromophe-
nyl- and octyl- sulfonamides when compared to the other primary
sulfonamides, might be related to their favorable values of logP
(Table 4).
Supplementary material
Details on data collection, refinement and crystallographic data
in CIF format for structures 1 and 3 have been deposited at the
Cambridge Crystallographic Data Centre, No. CCDC 977967 and
977968. Copies of this information may be obtained free of charge
from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
(fax: +44 1223 336 033; email: deposit@ccdc.cam.ac.uk or www:
http://www.ccdc.cam.ac.uk).
Acknowledgements
The allyl sulfonamides 1, 5 and 8 were the most active com-
pounds, showing logP values between 3.52 and 4.05. The electron
withdrawing substituents (F, Cl, Br) did not improve the activity of
the aromatic sulfonamides, except for the nitro group which
The authors thank the Brazilian agencies CAPES, FAPEMIG and
CNPq for financial support and students grants. We are also
grateful to Prof. Dr. J. Ellena of the Instituto de Física de São Carlos,
Universidade de São Paulo, Brazil, for the X-ray data collection.

E.C. Tavares et al. / Journal of Molecular Structure 1067 (2014) 43–51
51
Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S.
Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M.
Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A.
Pople, Gaussian 09, Revision B.04, Gaussian Inc, Pittsburgh PA, 2009.
[15] A.G. Pacheco, V.G.C. Abreu, H.A. de Abreu, D. Piló-Veloso, A.F.C. Alcântara,
Struct. Chem. 25 (2012) 703–710.
[16] F.J.L. Santos, A.F.C. Alcântara, D.L. Ferreira-Alves, D. Piló-Veloso, Struct. Chem.
19 (2008) 625–631.
[17] H.A. de Abreu, I.A.S. Lagos, G.P. Souza, D. Piló-Veloso, H.A. Duarte, A.F.C.
Alcântara, Org. Biomol. Chem. 6 (2008) 2713–2718.
[18] F.P.G. Euzébio, F.J.L. Santos, D. Piló-Veloso, A.F.C. Alcântara, A.L.G. Ruiz, J.E.
Carvalho, M.A. Foglio, D.L. Ferreira-Alves, A. Fátima, Bioorg. Med. Chem. 18
(2010) 8172–8177.
[19] G.P. Souza, C. Konzen, T.R.G. Simões, B.L. Rodrigues, A.F.C. Alcântara, H.O.
Stumpf, J. Mol. Struct. 1016 (2012) 13–21.
[20] A. Pérez-Rebolledo, I.C. Mendes, N.L. Speziali, P. Bertani, J.M. Resende, A.F.C.
Alcântara, H. Beraldo, Polyhedron 26 (2007) 1449–1458.
[21] S.R. Sridhar, R.V. Rajagopal, R. Rajavel, S. Masilamani, S. Narasimhan, J. Agric.
Food Chem. 51 (2003) 7596–7599.
[22] F.A. Cotton, P.F. Stokley, J. Am. Chem. Soc. 92 (1970) 294–302.
[23] N. Özbek, S. Alyar, S. Mamas, E. Sahin, N. Karacan, J. Mol. Struct. 1010 (2012) 1–
7.
[24] G. Usha, S. Selvanayagam, D. Velmurugan, K. Ravikumar, P. Jaisankar, P.C.
Srinivasan, Acta Cryst. E61 (6) (2005) o1916–o1918.
[25] S.D. Lindell, L.C. Pattenden, J. Shannon, Bioorg. Med. Chem. 17 (2009) 4035–
4046.
[26] L. Saíz-Urra, M.P. González, I.G. Collado, R. Hernández-Galán, J. Mol. Graph.
Model. 25 (2007) 680–690.
References
[1] (a) D. Basavaiah, G. Veeraraghavaiah, Chem. Soc. Rev. 41 (2012) 68–78;
(b) D. Basavaiah, R.S. Hyma, K. Padmaja, M. Krishnamacharyulu, Tetrahedron
55 (1999) 6971–6976;
(c) K.H. Kim, S.H. Kim, H.J. Lee, J.N. Kim, Adv. Synth. Catal. 355 (10) (2013)
1977–1983.
[2] C.G. Lima-Junior, M.L.A.A. Vasconcellos, Bioorg. Med. Chem. 20 (2012) 3954–
3971.
[3] (a) M. Remko, J. Mol. Struct.-Theochem. 944 (2010) 34–42;
(b) M. Remko, C. von der Lieth, Bioorg. Med. Chem. 12 (2004) 5395–5403;
(c) N. Özbek, H. Katırcıog˘lu, N. Karacan, T. Baykal, Bioorg. Med. Chem. 15
(2007) 5105–5109.
[4] J.T. Cole, J.C. Cole, K.E. Conway, J. Appl. Hortic. 7 (2005) 16–19.
[5] Z. Ma, T.J. Michailides, Crop Prot. 24 (2005) 853–863.
[6] H.S. Kim, H.S. Lee, J.N. Kim, Bull. Korean Chem. Soc. 30 (2009) 941–944.
[7] J. Cai, Z. Zhou, G. Zhao, C. Tang, Org. Lett. 4 (2002) 4723–4725.
[8] Enraf-Nonius COLLECT, Nonius BV, Delft, The Netherlands, 1997–2000.
[9] Z. Otwinowski, W. Minor, in: C.W. Carter Jr., R.M. Sweet (Eds.), Methods in
Enzymology, vol. 276, Academic Press, New York, 1997, p. 307.
[10] G.M. Sheldrick, Acta Crystallogr. A 64 (2008) 112–122.
[11] L.J. Farrugia, J. Appl. Crystallogr. 32 (1999) 837–838.
[12] C.F. Macrae, P.R. Edgington, P. McCabe, E. Pidcock, G.P. Shields, R. Taylor, M.
Towler, J.V.D. Streek, J. Appl. Crystallogr. 39 (2006) 453–457.
[13] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[14] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman
Jr., J.A. Montgomery, T. Vreven, T.K.N. Kudin, J.C. Burant, J.M. Millam, S.S.
Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox,
H.P. Hratchian, J.B. Cross, C. Adamo, C. Jaramillo, R. Gomperts, R.E. Stratmann,
O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K.