Similarities and differences in the crystal packing of methoxybenzyl and methoxyphenylethyl-1,3,4-oxadiazole-2(3H)-thiones

Article abstract of DOI:10.1039/c3ce42000k

This work reports the crystal and molecular structures of five 1,3,4-oxadiazol-2(3H)-thiones derived from 2, 3 and 4-methoxy substituted 2-phenylacetic acid and 2- and 4-methoxy substituted 3-phenylpropanoic acid. The methoxybenzyl-1,3,4-oxadiazol-2(3H)-thiones are V-shaped while the corresponding methoxyphenylethyl-systems are close to planar, which impacts the solid state molecular packing arrangement. For molecules 1-4, inversion related N-H...S hydrogen bonds generating R22(8) rings dominate the packing, supported by an eclectic mix of C-H...O, C-H...S, C-H...π and π...π contacts that stack the molecules into interconnected columns. In contrast, each of the two unique molecules in the asymmetric unit of 5 forms N-H...O contacts with like molecules augmented by C-H...S contacts for one molecule and C-H...O contacts for the other to generate planar layers that are interconnected though a series of π...π stacking interactions. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3ce42000k

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Similarities and differences in the crystal packing of
methoxybenzyl and methoxyphenylethyl-1,3,4-
oxadiazole-2(3H)-thiones†
Cite this: CrystEngComm, 2014, 16,
64
1
a
a
b
Imtiaz Khan, Aliya Ibrar and Jim Simpson*
This work reports the crystal and molecular structures of five 1,3,4-oxadiazol-2(3H)-thiones derived
from 2, and 4-methoxy substituted 2-phenylacetic acid and 2- and 4-methoxy substituted
-phenylpropanoic acid. The methoxybenzyl-1,3,4-oxadiazol-2(3H)-thiones are V-shaped while the
3
3
corresponding methoxyphenylethyl-systems are close to planar, which impacts the solid state molecular
2
2
packing arrangement. For molecules 1–4, inversion related N–H⋯S hydrogen bonds generating R
(8)
Received 3rd October 2013,
Accepted 6th November 2013
rings dominate the packing, supported by an eclectic mix of C–H⋯O, C–H⋯S, C–H⋯π and π⋯π contacts
that stack the molecules into interconnected columns. In contrast, each of the two unique molecules in
the asymmetric unit of 5 forms N–H⋯O contacts with like molecules augmented by C–H⋯S contacts for
one molecule and C–H⋯O contacts for the other to generate planar layers that are interconnected
though a series of π⋯π stacking interactions.
DOI: 10.1039/c3ce42000k
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wide variety of organisms, including plants, algae, fungi, and
Introduction
1
2–15
bacteria.
Strategies based on urease inhibition are the
1
,3,4-Oxadiazole derivatives form a class of heterocyclic com-
first treatment of infections caused by urease-producing
bacteria. In agriculture, high urease activity releases abnor-
mally large amounts of ammonia into the atmosphere after
urea application with resultant environmental problems and
pounds that have attracted significant interest in medicinal
and coordination chemistry and provide versatile lead mole-
cules for designing potential bioactive agents. They show a
variety of biological activities including antimicrobial, anti-
HIV, antitubercular, antimalarial, analgesic, anti-inflammatory,
anticonvulsant and hypoglycemic activity together with other
biological properties such as genotoxicity and lipid peroxi-
dation inhibition.
Recently, the research group of Iqbal and Rama extended
the chemistry of 1,3,4-oxadiazoles to encompass a variety
of substituted 1,3,4-oxadiazol-2(3H)-thiones, Scheme 1, with
additional CS functionality and methoxy substituents in
various positions on the benzyl and the phenylethyl ring
systems. These materials have been screened for urease
inhibition and, generally, have exhibited excellent urease
inhibition activities at least comparable to, and in a number
of cases significantly better than, drugs in current use.
1
6
economic stress. This further induces damage to plants
by depriving them of their essential nutrients and also as a
result of ammonia toxicity, leading to an increase in soil
1–7
1
,17
pH.
Control of the activity of urease through the use
8,9
of inhibitors could counteract these negative effects, and the
incorporation of additional potential ligand species in the
form of the thione S and methoxy O atoms increases the poten-
tial effectiveness of urease inhibition in these compounds.
Coordination complexes of 1,3,4-oxadiazole-2-thiones have
also attracted significant current interest but are strictly limited
to complexes in which the deprotonated amino N atom acts
1
0
1
8
as the ligand donor. A particular feature of the coordi-
nation chemistry of such derivatives, is the use of auxiliary
pyridine ligand substituents on the oxadiazolethione units to
1
9
Urease (EC 3.5.1.5; urea amidohydrolase) is
a
nickel-
form coordination polymers.
containing metalloenzyme that catalyzes the hydrolysis of
urea to ammonia and carbon dioxide. It is present in a
Structures of organic 1,3,4-oxadiazole-2(3H)-thione deriva-
1
1
20
tives are sparsely reported with only eighteen unique examples
21
in the Cambridge Structural Database (CSD). Of these, only
a
22
Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan
two had 5-substituted benzene rings. Seven additional deriva-
b
Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054,
tives in which the N–H proton is replaced with a variety of
New Zealand. E-mail: jsimpson@alkali.otago.ac.nz; Fax: +64 3 479 7906;
Tel: +64 3 479 7914
23
organic substituents are also found. Comparable benzyl and
phenylethyl structures however are completely arcane, with no
reports of the structures of any similar compounds. The five
molecules examined here (Scheme 1) allow us to investigate
†
Electronic supplementary information (ESI) available: Full bond length and
angle data. CCDC 964316–964320. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c3ce42000k
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Scheme 1 2-Methoxybenzyl, n = 1, 1; 3-methoxybenzyl, n = 1, 2; 4-methoxybenzyl, n = 1, 3; 2-methoxyphenylethyl, n = 2, 4; 4-methoxyphenylethyl, n = 2, 5.
the similarities and differences in crystal structure and packing
that occur as a result of variations in the links between the
methoxyphenyl and oxadiazole rings and changes in the
methoxy substitution patterns. An additional member of the
Fig. 1 (a) The structure of 1 showing the atom numbering with ellipsoids drawn at the 50% probability level. (b–d) Similar views of 2, 3 and 4.
e) The two unique molecules in the asymmetric unit of 5.
(
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2
24
series, 5-(3-methoxyphenethyl)-1,3,4-oxadiazole-2(3H)-thione, has
also been reported but, to date, has stubbornly resisted
attempts to obtain X-ray quality crystals.
forming R (8) loops in each case, Fig. 2, Table 2. This
2
1
0
synthon occurs in all three isomers in the methoxybenzyl
series, 1–3, but only in 4, the ortho-substituted isomer, of the
two methoxyphenylethyl derivatives 4 and 5.
In contrast, the para-methoxyphenylethyl derivative, 5,
favours N–H⋯O hydrogen bonds, Table 2, that link opposite
Results and discussion
Molecular structures
2
4
ends of like molecules to form C(11) chains that lie parallel
to (001) and run approximately along (11 ¯1 ), Fig. 3.
Compounds 1–5 (Scheme 1) were synthesized by a literature
1
0
Searches of the CSD reveal that, despite their predominance
among the molecules reported here, N–H⋯S inversion
dimers are not the synthons of choice for the majority
of 1,3,4-oxadiazol-2(3H)-thiones. Indeed, only two relatively
simple, planar derivatives, 5-(furan-2-yl)-1,3,4-oxadiazole-2(3H)-
procedure and have been characterized by microanalysis
and spectroscopic methods. For the structural study, single
crystals of 1–5 were grown at room temperature from ethanol
solution and their molecular structures are shown in Fig. 1a–e.
Selected bond lengths and angles are given in Table 1.
The three methoxybenzyl compounds are all V shaped with
dihedral angles 79.50(5)° for 1, 57.38(5)° for 2 and 71.27(3)°
for 3 between the benzene and oxadiazole rings. In sharp
contrast, the phenylethyl analogues are effectively flat with rms
deviations 0.0978, 0.0831 and 0.0932 Å from the mean planes
through all 15 non-hydrogen atoms of 4 and of the two unique
molecules of 5 respectively.
2
5
26
thione
and 5-phenyl-1,3,4-oxadiazole-2(3H)-thione
form
N–H⋯S dimers in their crystal structures. Perhaps surprisingly,
in view of the findings in this investigation, the database
also revealed that N–H⋯O contacts were significantly
22a,27
more prevalent with nine examples
among the eighteen
unique 1,3,4-oxadiazol-2(3H)-thione entries. However, there
2
8
was only one instance of an N–H⋯O contact involving
a methoxy-phenyl O atom such as occurs with 5. Eleven
1
,3,4-oxadiazol-2(3H)-thione derivatives formed N–H⋯N
Crystal packing
20a–20e,20g,20h,22a,27a,27b,27g
contacts,
sometimes in addition to
Of particular note here was
2
2a,27a,27b
Hydrogen bond distances and angles together with details of
π⋯π contacts for 1–5 are shown in Table 2. An immediate
feature of the packing in four of the five compounds, 1–4, is
the ready formation of inversion related N–H⋯S dimers
N–H⋯O interactions.
the presence of six N–H⋯N contacts involving N atoms
2
0a–20d
27a,27b
from pyridyl
or quinolin
substituents on the
oxadiazole-thione units.
Table 1 Selected bond lengths, (Å), and angles, (°), for 1–5
1
2
3
4
5A
5B
S2–C2
O1–C2
O1–C5
C2–N3
N3–N4
N4–C5
C5–C6
C6–C7
1.6548(19)
1.371(2)
1.375(2)
1.329(2)
1.388(2)
1.284(2)
1.491(2)
1.6568(15)
1.3652(17)
1.3760(17)
1.3262(19)
1.3854(17)
1.2821(19)
1.484(2)
1.6632(10)
1.6612(10)
1.3641(12)
1.3772(12)
1.3285(12)
1.3951(12)
1.2868(13)
1.4792(14)
1.5242(14)
1.648(3)
1.376(3)
1.645(3)
1.382(3)
1.384(3)
1.340(3)
1.390(3)
1.290(3)
1.468(4)
1.538(4)
1.3639(11)
1.3769(11)
1.3278(12)
1.3886(12)
1.2855(12)
1.4818(13)
1.382(3)
1.335(3)
1.398(3)
1.287(3)
1.471(4)
1.531(3)
C6–C11
C7–C11
C12–O12
O12–C121
C13–O13
O13–C131
C14–O14
O14–C141
S2–C2–O1
S2–C2–N3
O1–C2–N3
C2–N3–N4
C2–O1–C5
O1–C5–N4
N3–N4–C5
C11–C12–O12
C13–C12–O12
C12–O12–C121
C12–C13–O13
C14–C13–O13
C13–O13–C131
C13–C14–O14
C15–C14–O14
C14–O14–C141
1.513(2)
1.520(2)
1.5172(13)
1.5160(14)
1.3726(12)
1.4337(13)
1.525(4)
1.520(4)
1.372(2)
1.434(2)
1.3723(17)
1.4287(18)
1.3659(11)
1.4294(12)
1.380(3)
1.446(3)
1.376(3)
1.436(3)
124.07(19)
131.8(2)
104.2(2)
113.3(2)
106.32(19)
113.0(2)
103.1(2)
123.32(13)
132.00(14)
104.68(15)
112.71(14)
106.54(13)
112.57(15)
103.51(14)
115.09(15)
124.62(16)
116.95(14)
123.32(11)
131.51(12)
105.17(12)
112.66(12)
105.96(11)
113.04(13)
103.17(12)
123.54(7)
131.12(8)
105.34(8)
112.45(8)
106.04(7)
112.92(8)
103.20(8)
122.27(7)
123.73(19)
131.5(2)
104.8(2)
112.9(2)
106.14(19)
113.3(2)
102.9(2)
132.58(8)
105.13(8)
112.58(8)
106.40(7)
112.88(9)
103.01(8)
115.02(9)
123.79(9)
117.54(8)
123.94(13)
115.86(12)
117.03(11)
115.8(8)
124.28(8)
116.40(7)
116.1(2)
123.9(2)
118.6(2)
116.2(2)
124.8(2)
118.1(2)
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a
Table 2 Hydrogen bond distances (Å), angles (°) and π⋯π contacts for 1–5
Compound
D–H⋯A
D–H
H⋯A
D⋯A
∠D–H⋯A
1
1
(i)
N3–H3N⋯S2
0.88(2)
0.98
0.98
2.41(2)
2.64
2.69
3.2843(15)
3.274(2)
3.338(2)
3.413(2)
169.5(17)
123
124
1
(ii)
C121–H12B⋯O1
1
(iii)
C121–H12A⋯O12
1
(iv)
C6–H6A⋯Cg1
0.99
2.64
135
2
3
4
2
(i)
N3–H3N⋯S2
0.85(2)
0.99
0.98
2.42(2)
2.69
2.96
3.2668(14)
3.4894(18)
3.8098(16)
3.4989(9)
3.7312(9)
176.8(17)
138
146
2
(ii)
C6–H6A⋯O13
2
(iii)
C131–H13B⋯S2
2
2
(ii)
Cg2⋯Cg3
Cg3⋯Cg3
(iv)
3
(i)
N3–H3N⋯S2
0.892(15)
0.99
0.95
0.95
0.98
2.366(15)
2.89
2.64
2.81
2.71
3.2579(9)
3.7363(10)
3.3730(11)
3.555(10)
3.5715(11)
178.1(13)
143
134
136
148
3
(ii)
C6–H6A⋯S2
3
(iii)
C12–H12⋯O14
3
(iv)
C13–H13⋯Cg4
3
(v)
C141–H14A⋯Cg4
4
(i)
N3–H3N⋯S2
0.863(15)
0.99
0.95
2.383(15)
2.93
2.54
3.2427(9)
3.7586(11)
3.2954(12)
3.5021(14)
3.6901(6)
3.5453(6)
3.6022(11)
174.7(13)
142
137
4
(ii)
C6–H6A⋯S2
4
(iii)
C16–H16⋯O1
4
(iv)
C121–H12B⋯O12
0.98
2.71
138
4
4
(v)
Cg5⋯Cg5
Cg5⋯Cg6
(vi)
4
(vii)
C13–H13⋯Cg6
0.95
2.85
137
5
5
(i)
N3A–H3NA⋯O14A
N3B–H3NB⋯O14B
0.85(3)
0.82(3)
0.95
0.95
0.98
0.98
0.98
1.96(3)
1.98(3)
2.53
2.57
3.00
3.00
2.89
2.783(3)
2.774(3)
3.447(3)
3.462(3)
3.822(3)
3.830(3)
3.869(3)
3.8280(15)
3.6646(16)
3.7191(16)
3.8056(16)
3.451(3)
163(3)
161(3)
163
156
142
143
173
5
(i)
5
(ii)
C16A–H16A⋯O1A
5
(ii)
(iii)
(iii)
C16B–H16B⋯O1B
5
C141–H14B⋯S2A
5
C142–H14E⋯S2B
5
(iv)
C142–H14D⋯S2A
5
(v)
Cg7⋯Cg8
5
(v)
Cg7⋯Cg10
5
5
(v)
Cg8⋯Cg9
Cg9⋯Cg9
(vi)
5
(vii)
C142–H14F⋯Cg10
0.98
2.65
139
a
Symmetry codes: 1(i) = 1 − x, 1 − y, 1 − z; 1(ii) = 2 − x, −y, 1 − z; 1(iii) = 2 − x, 1 − y, 1 − z; 1(iv) = x, 1 − y, z; 2(i) = −x, −y, 1 − z; 2(ii) = 1/2 − x,
1/2 + y, 3/2 − z; 2(iii) = −x, −y + 1, 1 − z; 2(iv) = 1/2 − x, 1/2 + y, 3/2 − z; 3(i) = 1 − x, −1 − y, 1 − z; 3(ii) = 1 + x, y, z; 3(iii) = 3/2 − x, 1/2 + y, 1/2 − z;
(iv) = 3/2 − x, 1/2 + y, 1/2 − z; 3(v) = 5/2 − x, −1/2 + y, 1/2 − z; 4(i) = 1 − x, 3 − y, 1 − z; 4(ii) = x, −1 + y, z; 4(iii) = 1 − x, −1/2 + y, 3/2 − z; 4(iv) = 2 − x,
− y, 1 − z; 4(v) = 1 − x, 2 − y, 1 − z; 4(vi) = x, 1 + y, z; 4(vii) = 2 − x, −1/2 + y, 3/2 − z; 5(i) = 1 + x, −1 + y, z; 5(ii) = x − 1, y, z; 5(iii) = −2 + x, 1 + y, z;
(iv) = 1 − x, −y, 1 − z; 5(v) = 1 − x, −y, 1 − z; 5(vi) = 2 − x, −y, 2 − z, 5(vii) = −x, 1 − y, 2 − z. Centroids are defined as follows: Cg1 C11⋯C16 ring
−
3
1
5
of 1; Cg2 and Cg3 O1, C2, N3, N4, C5 and C11⋯C16 rings of 2; Cg4 C11⋯C16 ring of 3; Cg5 and Cg6 O1, C2, N3, N4, C5 and C11⋯C16 rings of 4;
Cg7, Cg8, Cg9 and Cg10 O1A, C2A, N3A, N4A, C5A and C11A⋯C16A and O1B, C2B, N3B, N4B, C5B and C11B⋯C16B rings of the two unique
molecules of 5.
Crystal packing for 1. 1 forms C–H⋯π hydrogen bonds
that stack pairs of the N–H⋯S inversion dimers along the
interaction, in this case between the oxadiazole ring and the
benzene ring so that such contacts play a significant role in
consolidating the crystal packing. A suitable separation for
aromatic rings to be considered as sensible π⋯π contacts
3
1
b axis, Fig. 4(a). Two weaker C–H⋯O contacts, Fig. 4(b),
involving the methoxy methyl group also add stability to
2
9,30
the structure of 1. Pairs of C121–H12A⋯O12 interactions
is <4.0 Å.
Here both Cg2⋯Cg3 and Cg3⋯Cg3 contacts
2
form R (6) rings while C121–H12B⋯O1 hydrogen bonds
are observed at 3.4989(9) Å and 3.7312(9) Å respectively,
where Cg2 is the centroid of the oxadiazole ring and Cg3 that
of the benzene ring. These link four adjacent molecules to
form almost orthogonal four rung ladder motifs that run
approximately along (043) and (04 ¯3 ) Fig. 5(a), and further
generate a two-dimensional network approximately parallel to
(10 ¯1 ), Fig. 5(b). Individual two-dimensional networks form
parallel layers along the c axis, Fig. 5(c). In common with the
other two methoxybenzyl derivatives, molecules of 2 stack also
along the a axis with molecules interleaved in a head to tail
fashion, Fig. 8(b).
2
2
24
2
enclose an R (16) loop. The net effect of these various
contacts is to stack the molecules along the
Fig. 8(a).
b axis,
Crystal packing for 2. In addition to the strong N–H⋯S
hydrogen bonds, C121–H13B⋯S2 and C6–H6A⋯O13 contacts
are also found in the crystal structure of 2. The former
2
2
24
generate inversion dimers with R
(22) ring motifs and also
place the contributing molecules in an orientation that allows
π⋯π stacking between the closely adjacent benzene rings.
Interestingly the C–H⋯O contact also bolsters a π⋯π
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Fig. 3 Chains of like molecules of 5 parallel to (001); 5(i) = 1 + x, −1 + y, z.
Fig. 2 Inversion dimers for (a) 1, 1(i) = 1 − x, 1 − y, 1 − z; (b) 2, 2(i) = −x, −y,
1
− z; (c) 3, 3(i) = 1 − x, 1 − y, 1 − z; (d) 4, 4(i) = 1 − x, 3 − y, 1 − z
with hydrogen bonds shown as blue dashed lines both here and in
subsequent figures.
Fig. 4 (a) C–H⋯Cg1 contacts for 1. Cg1 is the centroid of the
C11⋯C16 benzene ring with C–H⋯π contacts drawn as green dashed
lines and ring centroids displayed as coloured spheres. (b) C–H⋯O
hydrogen bonds for 1.
Crystal packing for 3. In the crystal of 3, C6–H6A⋯S2
4
4
hydrogen bonds link the inversion dimers forming R (14)
24
rings and generate corrugated chains along a, Fig. 6(a).
A C12–H12⋯O14 hydrogen bond also forms and bolsters a
C13–H13⋯Cg4 contact to the C11⋯C16 benzene ring of an
adjacent molecule. A further C141–H14A⋯Cg4 interaction
further aggregates molecules into columns along a, Fig. 6(b).
The net effect of these contacts is a three-dimensional network
structure with molecules stacked along the b axis, Fig. 8(c).
Crystal packing for 4. For 4, weak C121–H12B⋯O12
3
1
2
2
24
contacts form additional R (6) inversion dimers that link
the N–H⋯S dimers into extended planar sheets that run
approximately parallel to (423), Fig. 7(a). These sheets are
connected by inversion related π⋯π stacking interactions
between two adjacent oxadiazole rings (centroid Cg5;
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Fig. 6 (a) Chains of molecules of 3. (b) C–H⋯π contacts in 3. 3(i) = 1 − x,
−
1 − y, 1 − z; 3(ii) = 1 + x, y, z; 3(iii) = 3/2 − x, 1/2 + y, 1/2 − z; 3(iv) = 3/2 − x,
1
/2 + y, 1/2 − z.
Despite the number and complexity of the contacts in 4
the final overall picture of the packing is a relatively simple
three-dimensional network with molecules stacked in regular
interconnected columns along the b axis, Fig. 8(d).
Overall packing for 1–4. A common feature of the overall
packing for all four molecules with the common N–H⋯S
dimer motif is the formation of stacks with the inversion
dimers further interconnected by a variety of non-classical
C–H⋯S(O), C–H⋯π and π⋯π interactions Fig. 8(a–d).
Fig. 5 (a) π⋯π contacts in the structure of 2. Centroids of the
oxadiazole rings are shown as yellow spheres with those of the
benzene rings in red. π⋯π contacts are drawn as green dashed lines.
2
(ii) = 1/2 − x, −1/2 + y, 3/2 − z; 2(iii) = −x, −y + 1, 1 − z; 2(iv) = 1/2 − x,
/2 + y, 3/2 − z. (b) A two dimensional network parallel to (10 1¯ ).
Representative π⋯π contacts are drawn as green dashed lines.
c) Parallel layers along the c axis of 2.
1
(
Crystal packing for 5. Unlike the preceding four instances,
N–H⋯O contacts and π⋯π stacking interactions dominate
the packing for the planar 4-methoxyphenylethyl derivative,
5. The N–H⋯O hydrogen bonds form only between like
molecules of the two unique molecules that make up the
asymmetric unit of this structure. This leads to the formation
of independent chains of type A and type B molecules. Strong
classical N3A–H3NA⋯O14A and N3B–H3NB⋯O14B hydrogen
bonds join opposite extremities of like molecules to form
Cg5⋯Cg5 = 3.6902(6) Å) and between an oxadiazole and a
benzene ring (centroid Cg6; Cg5⋯Cg6 = 3.5452(6) Å). These
contacts are augmented by C6–H6A⋯S2 hydrogen bonds that
4
4
24
form R (14) rings and together serve to stack the molecules
along the b axis. Fig. 7(b). The plethora of contacts in
the crystal structure of this molecule is completed by
C16–H16⋯O1 and C7–H7⋯Cg6 contacts that form zig-zag
chains along a, Fig. 7(c).
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Fig. 7 (a) Sheets of molecules of 4 parallel to (423). (b) π⋯π contacts
for 4, shown as green dotted lines. (c) Chains along a generated by
C–H⋯O and C–H⋯π contacts for 4. 4(i) = 1 − x, 3 − y, 1 − z; 4(ii) = x,
−1 + y, z; 4(iii) = 1 − x, −1/2 + y, 3/2 − z; 4(iv) = 2 − x, 1 − y, 1 − z; 4(v) = 1 − x,
2 − y, 1 − z; 4(vi) = x, 1 + y, z; 4(vii) = 2 − x, −1/2 + y, 3/2 − z.
these chains along b. The chains are interconnected in two
discrete ways. For A type molecules, C16A–H16A⋯O1A hydro-
gen bonds link adjacent rows of A molecules to form a planar
layer parallel to (001). Weaker C141–H14B⋯S2A contacts
combine with the N–H⋯O and C–H⋯O contacts to generate
3
3
24
3 3
R (15) and R (20) loops and further consolidate the planar
layer structure, Fig. 9.
The S2B atom of molecule B is not involved in any close
contacts in the molecular plane. However, layers of type B
molecules are generated by a combination of N3B–H3NB⋯O14B
and C16B–H16B⋯O1B hydrogen bonds to yield a second planar
layer, again approximately parallel to (001) in this instance
4
4
24
with the formation of R (27) loops, Fig. 10.
The seeming demarcation of contacts to those between
like molecules in the planar layers breaks down when
contacts between the layers are considered. Inversion related
π⋯π stacking interactions between the benzene and oxadiazole
Fig. 8 Overall packing diagrams for 1 (a), 2 (b), 3 (c) and 4 (d). Where
necessary, representative C–H⋯π or π⋯π contacts are shown as green
dashed lines with the aromatic ring centroids displayed as coloured spheres.
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Fig. 9 Layers of A type molecules of 5 parallel to (001). 5(i) = 1 + x, −1
+
y, z; 5(ii) = x − 1, y, z; 5(iii) = −2 + x, 1 + y, z.
Fig. 10 Layers of B type molecules of 5 parallel to (001). 5(i) = 1 + x,
1 + y, z; 5(ii) = x − 1, y, z.
−
Fig. 12 Views of the three-dimensional network structure of 5. (a)
Layers generated from like molecules viewed along a. (b) Interleaved A
and B molecules viewed along b.
structure results. The ladder sequence is broken at this point
with a weak C142–H14F⋯Cg10 contact to an offset type B
molecule. π⋯π contacts to this B molecule restart another four
membered ladder. This together with a similar sequence of
contacts at the opposite end of the BAAB ladder builds a series
of offset ladder sequences along c, Fig. 11.
This description of course only identifies interactions
between individual A and B molecules. In reality, as described
previously, each A and B molecule is part of a planar layer of
like molecules each running approximately parallel to (001).
The offset ladder chains therefore serve to stack the layers
into an infinite three-dimensional lattice. Fig. 12 provides two
views of this lattice. Fig. 12(a) shows a set of 4 central layers
of BAAB molecules stabilized by Cg⋯Cg stacking interactions
between the benzene and oxadiazole rings of molecules
in adjacent layers. The top and bottom B layers are linked
to those above and below by C142–H14F⋯Cg10 contacts
producing offset layers that begin new BAAB sequences
along c. Viewing these layers along b, Fig. 12(b), reveals
interleaved layers of A and B molecules with molecules in
the alternate layers arranged in a head-to-tail fashion.
Fig. 11 Offset ladder sequences of molecules of 5 along c.
rings link a pair of adjacent A molecules arranged in a head to
tail fashion. Each of these form similar additional head to tail
π⋯π interactions with type B molecules, augmented by a
C142–H14D⋯S2A contacts and a four-membered BAAB ladder
C–H⋯π and/or π⋯π stacking interactions aid the crystal
packing in all of the molecules investigated here with 1 and 3
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Table 3 Crystal data and structure refinement of 1–5
1
2
3
4
5
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (°)
β (°)
C
10
H
10
N
2
O
2
S
C
10
H
10
N
2
O
2
S
C
10
H
10
N
2
O
2
S
C
11
H
12
N
2
O
2
S
C
11 12 2 2
H N O S
222.26
91(2)
0.71073
Monoclinic
P2 /n
11.6420(9)
4.6349(4)
18.8292(18)
90
95.453(5)
90
222.26
91(2)
0.71073
Monoclinic
P2 /n
8.6916(7)
13.2144(11)
8.9458(7)
90
93.960(4)
90
222.26
93(2)
0.71073
Monoclinic
P2 /n
7.5365(3)
5.5019(3)
24.9737(12)
90
92.956(2)
90
236.29
92(2)
0.71073
Monoclinic
P2 /c
9.8668(8)
6.9888(6)
16.1978(13)
90
98.855(4)
90
236.29
92(2)
0.71073
Triclinic
P¯1
1
1
1
1
7.8075(8)
11.2905(13)
13.2898(18)
88.359(7)
80.741(6)
73.514(6)
1108.5(2)
4
γ (°)
V (A )
3
1011.42(15)
4
1.460
1025.01(14)
4
1.440
1034.16(9)
4
1.428
1103.64(16)
4
1.422
Z
D
−3
calc (gcm
)
1.416
0.278
−
1
μ (mm
)
0.300
0.296
0.293
0.279
F (000)
Crystal size
θ range for data collection
Reflections collected
Independent
464
464
464
496
496
0.45 × 0.16 × 0.10
3.85–26.29
11 652
0.60 × 0.57 × 0.53
3.16–29.47
13 586
0.37 × 0.37 × 0.14
2.79–34.85
23 676
0.25 × 0.18 × 0.18
2.09–32.06
26 143
0.38 × 0.28 × 0.11
1.55–24.76
16 904
2046 [R(int) = 0.0421] 2825 [R(int) = 0.0449] 4485 [R(int) = 0.0351] 3854 [R(int) = 0.0377] 3699 [R(int) = 0.0439]
Observed
1662
2442
3962
3271
2673
Min. and max. transmission 0.7004, 0.7454
Data/restraints/parameters
Goodness-of-fit
0.6011, 0.7459
2825/0/140
1.052
0.7164, 0.7469
4485/0/140
1.046
0.7079, 0.7464
3854/0/149
1.036
0.6645, 0.7451
3699/0/297
1.051
2046/0/140
1.049
Final R indices [I > 2σ(I)]
R
1
= 0.0335,
wR = 0.0736
= 0.0457,
wR = 0.0795
R
1
= 0.0398,
wR = 0.0938
= 0.0479,
wR = 0.0993
R
1
= 0.0364,
wR = 0.0889
= 0.0423,
wR = 0.0933
R
1
= 0.0335,
wR = 0.0876
= 0.0407,
wR = 0.0924
R
1
= 0.0577,
wR = 0.1502
= 0.0788,
wR = 0.1733
2
2
2
2
2
R indices (all data)
R
1
R
1
R
1
R
1
R
1
2
2
2
2
2
Largest difference peak
0.283 and −0.256
0.349 and −0.304
0.497 and −0.282
0.497 and −0.216
1.219 and −0.382
−3
and hole (e Å
)
CCDC reference number
964316
964317
964318
964319
964320
displaying C–H⋯π contacts only while π stacking is particu-
larly prevalent in the structures of 2, 4 and 5 with contacts
between oxadiazole and benzene rings present in the packing
of all three molecules and augmented by contacts between
benzene rings for 2 and adjacent oxadiazole rings for 4.
Database searches (π⋯π contacts with Cg⋯Cg separations in
Despite their formulaic similarities, the five compounds
reported here display a significant array of intermolecular
interactions in stabilizing their crystal structures. Inversion
2
2
dimers with R (8) ring motifs generated through N–H⋯S
contacts are a common factor for 1–4 while the two unique
molecules in the asymmetric unit of 5 adopt N–H⋯O
contacts as their principal classical hydrogen bonding inter-
actions. The fact that the methoxybenzyl-1,3,4-oxadiazol-
2(3H)-thiones are all V shaped, whereas their methoxyphenylethyl
counterparts are effectively planar, also has implication
for the crystal packing with significant π⋯π contacts
more prevalent in the structures of the latter series. A
common feature of molecules 1–4 is their propensity to
stack in regular interconnected columns, while extensive
π⋯π stacking in compound 5 generates unusual offset
ladder sequences.
2
9,30
the range 4.0⋯3.0 Å
and C–H⋯π contacts with H⋯Cg
distances 3.0⋯2.4 Å ) of structures of other 1,3,4-oxadiazol-
(3H)-thiones show C–H⋯π contacts to be relatively
rare with only three occurrences each involving CH ⋯π
32
2
2
2
0e,27a,27f
interactions.
π⋯π contacts are more plentiful
with nine unique instances, the most common being four
examples of contacts between oxadiazole and benzene
2
2,26,27g
rings.
However, none of these display the ladder stack-
ing motifs favoured by 2 and 5. Three instances of contacts
between two oxadiazole rings are observed with two of them
2
0g,20h,27b
augmented by benzene to benzene stacking.
with
the picture completed by an unsupported stacking between
2
0h
two oxadiazole rings.
Experimental section
Materials and crystal growth
Conclusions
All compounds were synthesized by a previously published
1
0
Structures of 1,3,4-oxadiazol-2(3H)-thiones are not abundant
and the series of molecules reported here provides an
opportunity to compare the crystal packing behaviour across
a series of novel methoxybenzyl and methoxyphenylethyl-
procedure and characterized by elemental analysis and
spectroscopic methods and the data obtained were found
10
to be consistent with those observed in literature. For the
structural study, the compounds were recrystallized from
their respective ethanol solutions.
1
,3,4-oxadiazol-2(3H)-thiones with pharmaceutical potential.
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X-ray structure determination
13 H. L. Mobley and R. P. Hausinger, Microbiol. Mol. Biol. Rev.,
1
989, 53, 85.
The X-ray measurements for 1–5 were carried out on a Bruker
APEXII Kappa CCD single crystal diffractometer equipped
1
1
4 H. D. Reuter, Phytomedicine, 1995, 2, 73.
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with a graphite monochromator. MoK
α
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was used for all of the collections, which were controlled by
33
APEX2 with data collected at 91–93(2) K. Data were corrected
33
for Lorentz and polarization effects using SAINT and multi-
33
scan absorption corrections were applied using SADABS. The
34
structures were solved by direct methods (SHELXS-97) and
34
refined using full-matrix least-squares procedures (SHELXL-97
35
and Titan2000). All non-hydrogen atoms were refined aniso-
tropically and all hydrogen atoms bound to carbon were placed
in the calculated positions, and their thermal parameters
were refined isotropically with Ueq = 1.2–1.5 Ueq(C). The N–H
hydrogen atoms were located in difference Fourier maps
and their coordinates were refined with Ueq = 1.2 Ueq(N).
Compound 5 crystallised with two unique but closely similar
1
1
7 J. M. Bremenr, Fert. Res., 1995, 42, 321.
8 See for example: (a) A. Bharti, M. K. Bharty, S. Kashyap,
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5
0, 582; (b) M. K. Bharty, A. Bharti, R. K. Dani, R. Dulare,
3
6
P. Bharati and N. K. Singh, J. Mol. Struct., 2012, 1011, 34; (c)
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molecules, designated A and B, in the unit cell. These overlay
with an rms deviation of 0.1105 Å and the numbering scheme
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36
plots and packing diagrams were drawn using Mercury and
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7
additional metrical data were calculated using PLATON.
1
9 See for example: (a) Z.-H. Zhang, Y.-L. Tian and Y.-M. Guo,
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Details of the X-ray measurements and crystal data for all of
the complexes are given in Table 3.
Acknowledgements
5
785; (d) Y.-T. Wang, W.-Z. Wan, G.-M. Tang, Z.-W. Qiang
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