2-[(E)-(4-Hydroxy-3-methoxybenzyl-idene)amino]-N-(2-methylphenyl)-4,5,6, 7-tetrahydro-1-benzothiophene-3-carboxamide

Article abstract of DOI:10.1107/S0108270108001133

The title compound, C24H24N2O3S, exhibits anti-fungal and anti-bacterial properties. The compound crystallizes with two mol-ecules in the asymmetric unit, with one mol-ecule exhibiting orientational disorder in the crystal structure with respect to the cy

Full text of DOI:10.1107/S0108270108001133

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide group.
This molecular skeleton is divided into three parts, namely the
cyclohexene-fused thiophene group, the N-phenyl part and
the benzylideneamino group. It was observed that the cyclo-
hexene ring is ordered in all the above determined crystal
structures. In one such structure determination, viz. 2-({(1E)-
[4-(dimethylamino)phenyl]methylene}amino)-N-(4-methyl-
phenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
(Vasu et al., 2003), the asymmetric unit contains two mol-
ecules. It is indeed noteworthy that in the title compound, (I),
although it crystallizes with two molecules (A and B) in the
asymmetric unit (Fig. 1), one molecule exhibits orientational
disorder (molecule B) in the crystal structure. The disorder
could be well resolved, with the cyclohexene rings (C25/C26B/
C27A/C28±C30 and C25/C26A/C27B/C28±C30) existing in
two independent conformations with a population ratio of 1:1.
With this background, and in order to compare with our
previous studies the changes in molecular conformation and
associated intermolecular interactions due to the presence of
different substituents on the invariant group, the crystal
structure analysis of compound (I) has been carried out.
ISSN 0108-2701
2-[(E)-(4-Hydroxy-3-methoxybenzyl-
idene)amino]-N-(2-methylphenyl)-
4,5,6,7-tetrahydro-1-benzothiophene-
3-carboxamide
Vasu,a K. A. Nirmala,b Deepak Chopra,c* M. D.
Lakshmand and J. Saravanane
aVivekananda Degree College, Bangalore 560 055, Karnataka, India, bDepartment of
Physics, Bangalore University, Bangalore 560 056, Karnataka, India, cSolid State and
Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, Karnataka,
India, dDepartment of Physics, Seshadripuram College, Bangalore 560 020,
Karnataka, India, and eMS Ramaiah College of Pharmacy, Bangalore 560 054,
Karnataka, India
Correspondence e-mail: deepak@sscu.iisc.ernet.in
Received 29 November 2007
Accepted 11 January 2008
Online 23 February 2008
The title compound, C24H24N2O3S, exhibits antifungal and
antibacterial properties. The compound crystallizes with two
molecules in the asymmetric unit, with one molecule
exhibiting `orientational disorder' in the crystal structure with
respect to the cyclohexene ring. The o-toluidine groups in both
molecules are noncoplanar with the respective cyclohexene-
fused thiophene ring. In both molecules, there is an intra-
molecular NÐHÁ Á ÁN hydrogen bond forming a pseudo-six-
membered ring which locks the molecular conformation and
eliminates conformational ¯exibility. The crystal structure is
stabilized by OÐHÁ Á ÁO hydrogen bonds; both molecules in
the asymmetric unit form independent chains, each such chain
consisting of alternating `ordered' and `disordered' molecules
in the crystal lattice.
The thiophene ring of (I) is essentially planar, with
Ê
maximum deviations of 0.005 (3) and 0.017 (3) A for atoms
C9 and C31, respectively, in the two molecules. The six-
membered cyclohexene ring adopts a half-chair conformation,
with atoms C13 and C14 deviating from the C10/C11/C12/C15
Ê
plane by 0.228 (4) and 0.408 (5) A in molecule A; the
corresponding displacements for atoms C27A and C26B (of
the major conformer in molecule B) from the C25/C28±C30
Ê
plane are 0.23 (2) and 0.51 (2) A, respectively. The ring-
puckering parameters (Cremer & Pople, 1975) generated by
PLATON (Spek, 2003) for ꢀthe cyclohexene ꢀring are Q(2) =
Comment
Ê
The design of compounds possessing important pharmaco-
logical properties, such as antibacterial, anticancer, anti-
in¯ammatory and antitoxic activities, is an important area of
research. In this respect, Schiff bases (Pellis & West, 1968;
Cohen et al., 1977; Csaszar & Morvay, 1983; Lakshmi et al.,
1985) and their related thiophene derivatives (El-Maghraby et
al., 1984; Dzhurayev et al., 1992; Gewald et al., 1966) have been
synthesized and found to exhibit such biological activities. In
this context, sulfur-containing Schiff bases are the most
effective. In view of the medicinal applications of such classes
of compounds, single-crystal structure determinations of a
series of biologically active thiophene-3-carboxamide deriva-
tives have been performed (Vasu et al., 2003). In most of these
structure determinations, the molecular scaffold which
remains invariant is the 2-[(E)-benzylideneamino]-N-phenyl-
0.324 (3) A, '(2) = 200.2 (6) and ꢀ = 49.8 (4) in molecule A,
ꢀ
Ê
with corresponding values of 0.39 (2) A, 88.0 (12) and
131.9 (12)ꢀ in molecule B (major conformer).
The bond angles C20ÐC21ÐC23 and C42ÐC47ÐC46 in
molecules A and B are 116.9 (2) and 117.06 (3)ꢀ, respectively,
which deviate signi®cantly from the ideal value of 120ꢀ. This
deviation is due to the electron-donating inductive effect of
the methyl group, and similar variations in bond angles have
also been observed in 2-[(E)-(4-chlorophenyl)methylene-
amino]-N-(X-methylphenyl)-4,5,6,7-tetrahydro-1-benzothio-
phene-3-carboxamide (where X = 2 and 3; Vasu et al., 2004a),
and in 2-{[(E)-(4-methoxyphenyl)methylene]amino}-N-(3-
methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbox-
amide and N-(4-methylphenyl)-2-{[(E)-(4-methylphenyl)-
methylene]amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-car-
o184 # 2008 International Union of Crystallography
DOI: 10.1107/S0108270108001133
Acta Cryst. (2008). C64, o184±o186

organic compounds
boxamide (Vasu et al., 2004b). Similarly, the bond angles C8Ð
N1ÐC7 [121.9 (2)ꢀ] and C16ÐN2ÐC23 [123.9 (2)ꢀ] in mol-
ecule A around the iminomethyl N and amide N atoms are
different, indicating delocalization of the N-atom lone pair of
electrons. The corresponding bond angles C41ÐN4ÐC42 and
C31ÐN3ÐC32 in molecule B are 124.2 (2) and 122.3 (2)ꢀ,
respectively. This is further demonstrated by the bond lengths
in the carboxamide and imine groups being signi®cantly
different. In molecule A, the C16ÐN2 and C8ÐN1 bond
coplanar with the thiophene ring in both molecules A and B,
the corresponding dihedral angles being 176.3 (1) and
172.1 (1)ꢀ, respectively. It is noteworthy that, in the case of
2-{[(E)-(4-methoxyphenyl)methylene]amino}-N-(3-methyl-
phenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
and N-(4-methylphenyl)-2-{[(E)-(4-methylphenyl)methylene]-
amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
(Vasu et al., 2004b), the m-toluidine and p-toluidine rings are
coplanar with the thiophene rings because of the stabilization
imparted by the electron delocalization and the absence of
steric interactions. The introduction of one methyl group into
the N-phenyl ring in the ortho and meta positions, as in
the case of 2-[(E)-(4-chlorophenyl)methyleneamino]-N-(2-
methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbox-
amide (Vasu et al., 2004a), causes loss of planarity due to steric
interaction between the methyl group and the benzene H
atoms bonded to the imine group. The dihedral angle between
the mean planes of the m-toluidine and thiophene rings is
18.4 (1)ꢀ, whereas that between the o-toluidine and thiophene
rings is 12.9 (1)ꢀ. On addition of an F atom, as in the case of
2-[(E)-benzylideneamino]-N-(2-¯uorophenyl)-4,5,6,7-tetrahy-
dro-1-benzothiophene-3-carboxamide (Vasu et al., 2005), the
torsion angle is 151.8 (2)ꢀ between the o-¯uorophenyl and
thiophene groups, indicating the important role of steric
hindrance in molecular conformation. This deviation from
planarity is further increased when a methoxy group is
introduced on the phenyl ring attached to the imine group, as
re¯ected in the values of the dihedral angles observed here.
The conformations of both molecules in the asymmetric
unit of (I) are stabilized by intramolecular NÐHÁ Á ÁN
hydrogen bonds which lock the molecular conformations. The
crystal structure is stabilized by intermolecular OÐHÁ Á ÁO
hydrogen bonds involving the phenolic H atom and the
carbonyl ring, forming C(12) chains (Bernstein et al., 1995)
along the crystallographic c axis related by a glide plane (Fig. 2
and Table 2). From the packing characteristics, it is interesting
to note that the ordered molecule (A) forms molecular chains
involving OÐHÁ Á ÁO hydrogen bonds (involving atoms H1O
Ê
lengths are 1.342 (3) and 1.384 (3) A, respectively. The cor-
responding values in molecule B (C41ÐN4 and C31ÐN3) are
Ê
1.343 (3) and 1.388 (3) A, respectively, indicating that the
electronic and steric environments around these groups are
different (Table 1). Similarity in bond lengths has been
observed previously in analogous systems (Vasu et al., 2003,
2004a,b; Kumar et al., 2005).
The angles between the mean planes of the o-toluidine and
thiophene rings are 58.6 (1) and 64.4 (1)ꢀ in molecules A and
B, respectively, indicating suf®cient deviation from coplanarity
to minimize steric repulsion between the methoxy group and
the H atoms of the benzene ring (atoms H17 and H18 in
molecule A, and H43 and H44 in molecule B). This is further
demonstrated by the torsion angle C17ÐC23ÐN2ÐC16
about the C23ÐN2 bond in molecule A [ 107.6 (3)ꢀ] and
C43ÐC42ÐN4ÐC41 about the C42ÐN4 bond in molecule B
[ 102.7 (3)ꢀ]. The benzylideneamino group is essentially
Figure 1
Views of the two molecules (B top and A bottom) of (I), showing the
atom-labelling scheme. Displacement ellipsoids are drawn at the 50%
probability level. Dotted lines depict intramolecular NÐHÁ Á ÁN hydrogen
bonds. H atoms not involved in these hydrogen bonds have been omitted
for clarity.
Figure 2
A packing view of the molecules, along the [001] direction, showing the
OÐHÁ Á ÁO hydrogen bonds (dotted lines). Molecules labelled with an
)
2
1
2
1
asterisk (*) or a hash (#) are at the symmetry positions (x
,
y + 12, z
1
1
2
and (x + , y + , z 12), respectively.
2
ꢁ
Acta Cryst. (2008). C64, o184±o186
Vasu et al. C24H24N2O3S o185

organic compounds
and O6) with disordered molecules on either side. Similarly, in
the parallel chain along the [001] direction, the disordered
molecule B forms chains with ordered molecules via OÐ
HÁ Á ÁO hydrogen bonds (involving atoms H4O and O3). The
crystal structure is stabilized by van der Waals forces between
parallel layers of molecules (Vasu et al., 2003).
In conclusion, the effect of different substituents on the
conformational preferences in a series of carboxamide deri-
vatives has been highlighted. Packing is mainly governed by
strong hydrogen bonds together with van der Waals inter-
actions.
The H atoms of the phenolic O atom, the amide N atom and the C
atom connected to the imine N atom were located in a difference
Fourier map and re®ned isotropically. The NÐH and OÐH bond
Ê
lengths are in the ranges 0.81 (2)±0.82 (2) and 0.84 (4)±0.86 (4) A,
respectively. The disordered C26 and C27 atoms of the cyclohexene
ring in molecule B were split with an initial occupany of 0.5 assigned
to each. The H atoms on C25 and C28 were also split with occu-
pancies of 0.5 and ®xed using the riding model. The remaining H
atoms were placed in calculated positions and allowed to ride on
Ê
their parent C atoms, with CÐH = 0.93±0.97 A and Uiso(H) = 1.2 or
1.5Ueq(C).
Data collection: SMART (Bruker, 2000); cell re®nement: SAINT
(Bruker, 2000); data reduction: SAINT; program(s) used to solve
structure: SIR92 (Altomare et al., 1993); program(s) used to re®ne
structure: SHELXL97 (Sheldrick, 2008); molecular graphics:
ORTEP-3 for Windows (Farrugia, 1997) and CAMERON (Watkin et
al., 1993); software used to prepare material for publication:
PLATON (Spek, 2003).
Experimental
The title compound was synthesized using the Gewald reaction
(Gewald et al., 1966). o-Cyanotoluidine (0.04 mol) was re¯uxed with
ethyl methyl ketone in the presence of sulfur at 313±323 K for 1 h.
The product was then reacted with 4-hydroxy-5-methoxybenzalde-
hyde in an equimolar ratio in the presence of ethanol, which yielded
the title compound (68%). This was puri®ed by recrystallization from
ethyl acetate by slow evaporation, yielding orange needle-shaped
crystals of (I).
The authors thank Professor T. N. Guru Row, Indian
Institute of Science, Bangalore, and the Department of
Science and Technology, India, for data collection on the CCD
facility under the IRHPA±DST scheme. Vasu thanks Viveka-
nanda Degree College for support and DC thanks the CSIR
and IISc for a Senior Research Fellowship.
Crystal data
3
Ê
C24H24N2O3S
Mr = 420.52
V = 4271 (4) A
Z = 8
Monoclinic, P21=n
Mo Kꢂ radiation
ꢃ = 0.18 mm
T = 290 (2) K
0.18 Â 0.09 Â 0.08 mm
1
Ê
a = 14.817 (8) A
Ê
b = 13.701 (8) A
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: AV3133). Services for accessing these data are
described at the back of the journal.
Ê
c = 22.224 (13) A
ꢁ = 108.807 (11)ꢀ
Data collection
Bruker SMART CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
Tmin = 0.936, Tmax = 0.986
30379 measured re¯ections
7512 independent re¯ections
4900 re¯ections with I > 2ꢄ(I)
Rint = 0.037
References
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Re®nement
Bruker (2000). SMART (Version 5.0) and SAINT (Version 6.02). Bruker AXS
Inc., Madison, Wisconsin, USA.
R[F2 > 2ꢄ(F2)] = 0.053
wR(F2) = 0.134
S = 1.02
7512 re¯ections
587 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
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3
Ê
Áꢅmax = 0.28 e A
3
Ê
0.25 e A
Áꢅmin
=
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Ê
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N1ÐC7
N1ÐC8
N2ÐC16
N2ÐC23
1.283 (3)
1.384 (3)
1.342 (3)
1.431 (3)
N3ÐC32
N3ÐC31
N4ÐC41
N4ÐC42
1.277 (3)
1.388 (3)
1.344 (3)
1.424 (3)
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È
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Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
Cg1 is the centroid of the C17±C23 ring.
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
Vasu, Nirmala, K. A., Chopra, D., Mohan, S. & Saravanan, J. (2004b). Acta
Cryst. C60, o636±o638.
N4ÐH4NÁ Á ÁN3
N2ÐH2NÁ Á ÁN1
O4ÐH4OÁ Á ÁO3i
O1ÐH1OÁ Á ÁO6ii
C35ÐH35Á Á ÁCg1iii
0.81 (3)
0.82 (3)
0.86 (4)
0.88 (4)
0.93
2.05 (3)
2.06 (3)
1.83 (4)
1.82 (4)
2.89
2.738 (3)
2.748 (4)
2.683 (3)
2.697 (3)
3.670 (3)
143 (2)
141 (2)
171 (4)
174 (3)
143
Vasu, Nirmala, K. A., Chopra, D., Mohan, S. & Saravanan, J. (2005). Acta
Cryst. E61, o236±o238.
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Watkin, D. M., Pearce, L. & Prout, C. K. (1993). CAMERON. Chemical
Crystallography Laboratory, University of Oxford, England.
1
2
Symmetry codes: (i) x
;
y ‡ 12; z 12; (ii) x ‡ 21; y ‡ 21; z 12; (iii) x ‡ 1; y; z.
ꢁ
o186 Vasu et al. C24H24N2O3S
Acta Cryst. (2008). C64, o184±o186