Synthesis and crystal structure of 2-(4-Fluorobenzyl)-6-phenylimidazo[2,1- b][1,3,4]thiadiazole-5-carbaldehyde

Article abstract of DOI:10.1080/15421406.2010.526556

The crystal and molecular structure of 2-(4-fluoro-benzyl)-6-phenyl- imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde is described. The compound crystallizes in the monoclinic space group P2¹/n with a=7.419(3), A b=8.287(3), Ac=25.734(10)A, β=91

Full text of DOI:10.1080/15421406.2010.526556

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Synthesis and Crystal Structure of 2-(4-
Fluorobenzyl)-6-Phenylimidazo[2,1-b]
[1,3,4]Thiadiazole-5-Carbaldehyde
Afshan Banu a , Ravi S. Lamani b , I. M. Khazi b & Noor Shahina
Begum a
a Department of Studies in Chemistry , Bangalore University ,
Bangalore, India
b Department of Chemistry , Karnatak University , Dharwad, India
Published online: 14 Dec 2010.
To cite this article: Afshan Banu , Ravi S. Lamani , I. M. Khazi & Noor Shahina Begum (2010) Synthesis
and Crystal Structure of 2-(4-Fluorobenzyl)-6-Phenylimidazo[2,1-b][1,3,4]Thiadiazole-5-Carbaldehyde,
Molecular Crystals and Liquid Crystals, 533:1, 141-151, DOI: 10.1080/15421406.2010.526556
To link to this article: http://dx.doi.org/10.1080/15421406.2010.526556
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Mol. Cryst. Liq. Cryst., Vol. 533: pp. 141–151, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421406.2010.526556
Synthesis and Crystal Structure of
2-(4-Fluorobenzyl)-6-Phenylimidazo-
[2,1-b][1,3,4]Thiadiazole-5-Carbaldehyde
AFSHAN BANU,1 RAVI S. LAMANI,2 I. M. KHAZI,2
AND NOOR SHAHINA BEGUM1
1Department of Studies in Chemistry, Bangalore University,
Bangalore, India
2Department of Chemistry, Karnatak University, Dharwad, India
The crystal and molecular structure of 2-(4-fluoro-benzyl)-6-phenyl-imidazo[2,1-
b][1,3,4]thiadiazole-5-carbaldehyde is described. The compound crystallizes in
˚
˚
the monoclinic space groupꢀ P21=n with a ¼ 7.419(3)A, b ¼ 8.287(3)A,
is stabilized by intermolecular C-H . . . N, C-H . . . O, and C-H . . . F interactions.
3
˚
˚
c ¼ 25.734(10)A, b ¼ 91.686(8) , V ¼ 1,581.6(10)A , z ¼ 4. The crystal structure
Keywords C-H . . . N, C-H . . . O, and C-H . . . F weak interactions; crystal struc-
ture; imidazole thiadiazole derivative
Introduction
Imidazo[2,1-b][1,3,4]thiadiazole derivatives with pharmacophoric substituents
have promising biological and pharmacological activities, because the imidazo-
[2,1-b][1,3,4]thiadiazole ring is bioisosteric with the imidazo[2,1-b][1,3,4]thiazole ring
present in the well-known anthelmintic drug Tetramisole [1]. Consequently, a large
number of imidazo[2,1-b][1,3,4]thiadiazole derivatives have been reported to possess
diverse pharmacological properties such as anticancer [2], antitubercular [3], antibac-
terial [4], antifungal [5], anticonvulsant, analgesic [6], and antisecretory [7] activities.
Moreover, much interest has been focused on the anti-inflammatory [8], cardiotonic
[9], diuretic [10], and herbicidal [11] activities displayed by compounds incorporating
this heterocyclic system. In the field of modern medicinal chemistry it has been found
that the fluorinated compounds in general, and fluorinated heterocyclic compounds
in particular, are of much interest. It is reported that if a fluorine atom is incorpor-
ated into these compounds, the course of the reaction as well as the biological
properties are altered. The oxidative and thermal stability of these compounds
increases due to accumulation of fluorine atoms on carbon. These fluorinated drugs
possess metabolically nondegradable properties leading to an increase in lipid solu-
bility, which will further enhance the rate of absorption and transport of the drug
Address correspondence to Dr. Noor Shahina Begum, Department of Chemistry, Central
College Campus, Dr. B.R. Ambedkar Street, Bangalore University, Bangalore 560001,
Karnataka, India. E-mail: noorsb@rediffmail.com
141

142
A. Banu et al.
in vivo [12]. In view of the above facts and in continuation of our search for various
biologically active molecules [3,13,14], we attempted the synthesis and structure
analysis of the title compound. Additionally, it is an intermediate required for the
synthesis of thiazolidine-2,4-dione derivative, which is an expected antidiabetic
agent.
Synthesis and Method of Crystallization
The title compound was prepared in two stages as shown in Scheme 1. The reaction of
2-amino-5-(4-fluorobenzyl)-1,3,4-thiadiazole [15] (1) and phenacyl bromide (2) in boil-
ing ethanol afforded the 2-(4-fluorobenzyl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole (3)
as hydrobromide salt, which was neutralized by sodium carbonate solution to get the
free base. It was subjected to Vilsmeier-Haack reaction to yield 2-(4-fluorobenzyl)-6-
phenylimidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4). The structures of the
synthesized compounds were established by analytical and spectral data and confirmed
by X-ray crystal structure analysis.
Preparation of 2-(4-Fluorobenzyl)-6-Phenylimidazo[2,1-b][1,3,4]Thiadiazole(3)
A mixture of equimolar quantities of 2-amino-(4-fluorobenyl)-1,3,4-thiadiazole (1)
(2.69, 0.013 mol) and phenacyl bromide (2) compound (2.4 g, 0.01 mol) was refluxed
in dry ethanol for 16 h. The excess of solvent was distilled off and the solid hydro-
bromide salt that separated was collected by filtration, suspended in water, and
neutralized by aqueous sodium carbonate solution to get free base (3). It was filtered,
washed with water, dried, and recrystallized from ethanol.
Preparation of 2-(4-Fluorobenzyl)-6-Phenylimidazo [2,1-b] [1,3,4]Thiadiazole
Carbaldehyde (4)
Vilsmeier Haack reagent was prepared by adding phosphorous oxychloride (3 mL) in
dimethylformamide (20 mL) at 0ꢀC with stirring. At the same temperature,
2-(4-fluorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole (3) (2.5 g, 0.008 mol) was
added to the reagent and stirred at 0ꢀC–5ꢀC for 30 min. The mixture was further stir-
red for 2 h at room temperature and then at 60ꢀC for additional 2 h. The reaction
mixture was cooled in an ice-water bath and quenched with 5 mL water. The reaction
Scheme 1. Preparation of compound 4.

Crystal Structure
143
mixture was basified with aq. sodium carbonate (10%) solution with cooling and
further stirred at 80ꢀC–90ꢀC for 2 h. After cooling, the mixture was diluted with
water and extracted with chloroform (30 mL ꢁ 3). The combined extracts were
washed with water (100 mL ꢁ 3) and dried over anhydrous sodium sulfate. Solvent
was removed under vacuum and the solid obtained was recrystallized from chloro-
form to afford yellow crystals in excellent yields.
Experimental
Melting points were determined in open capillaries. Infrared (IR) spectra was
recorded on Nicolet Fourier transform infrared (FTIR) 410 spectrophotometer,
1H nuclear magnetic resonance (NMR) spectra were recorded on a Varian
RXZ-300 MHz spectrometer University Science Instrument Centre, Karnatak
University Dharwad, Karnataka using tetramethyl silane (TMS) as internal
standard.
Table 1. Crystal data and structure refinement
CCDC deposit no.
Empirical formula
Formula weight
Temperature
693225
C18H12FN3OS
336.36
293(2) K
0.71073
˚
Wavelength (A)
Crystal system
Space group
Unit cell dimensions
Monoclinic
P21=n
˚
a (A)
7.419(3)
8.287(3)
25.734(10)
91.686(8)
1581.6(10)
˚
b (A)
˚
c (A)
b (ꢀ)
Volume (A )
3
˚
Z
4
1.413
0.225
692
Calculated density (Mg=m3)
Absorption coefficient (mmꢂ1
F(000)
)
Crystal size
Theta range for data collection
Limiting indices
0.4 mm ꢁ 0.35 mm ꢁ 0.3 mm
2.58–28.37ꢀ.
ꢂ9 ꢃ h ꢃ 9,
ꢂ10 ꢃ k ꢃ 11,
ꢂ18 ꢃ l ꢃ 34
Reflections collected=unique
Completeness to theta
Refinement method
10,140=3,876 [R(int) ¼ 0.0476]
28.37 98.3%
Full-matrix least-squares on F2
3,876=0=241
0.961
Data=restraints=parameters
Goodness-of-fit on F2
Final R indices [I > 2r(I)]
R indices (all data)
R1 ¼ 0.0559, wR2 ¼ 0.1318
R1 ¼ 0.1175, wR2 ¼ 0.1674
0.307 and ꢂ0.215
ꢂ3
˚
Largest diff. peak and hole (eA
)

144
A. Banu et al.
Physical Measurements
The infrared spectra of imidazo[2,1-b][1,3,4]thiadiazole do not contain an absorption
band due to carbonyl and amino functionalities, confirming the formation of imida-
zothiadiazole. The 1H NMR spectra (CDCl3) showed appropriate signals due to dif-
ferent protons present in the molecule. The formylation product showed the band
due to aldehydic proton in the NMR spectrum. The absence of a singlet due to
C5-H was considered as the confirmation of the formylation at C5.
Compound (3), yield 75%, m.p. 168–170ꢀC; IR (KBr) ncmꢂ1: 3,124, 2,923, 2,853,
1
1,602, 1,507; H NMR (300 MHz, CDCl3) d: 4.29 (s, 2H, CH2), 7.06–7.44 (m, 7H,
Ar-H), 7.83 (d, J ¼ 7.2 Hz, 2H, Ar-H), 7.98 (s, 1H, C5-H, imidazole), 13C NMR
(150 MHz, CDCl3) d: 43.2, 116.9, 121, 126, 128, 129.6, 130.1, 132.1, 132.6, 135.5,
160.1, 136.5, 1648. Anal. calcd. for C17H12FN3S: C, 66.01; H, 3.88; N, 13.59; Found:
C, 66.10; H, 3.82; N, 13.62%.
Compound (4), yield 75%, m.p. 110–112ꢀC; IR (KBr) ncmꢂ1: 2,924, 2,854, 1,676,
1
1,602, 1,523; H NMR (300 MHz, CDCl3) d: 4.45 (s, 2H, CH2), 7.07–7.13 (t, 1H,
J ¼ 8.52 Hz, Ar-H), 7.32–7.84 (m, 8H), 10.04 (s, 1H, CHO). 13C NMR (150 MHz,
CDCl3) d: 46.5, 116.1, 125.0, 127.6, 131.2, 132.0, 134.7, 135.0, 135.9, 136.4, 144.1,
Table 2. Atomic coordinates (ꢁ104) and equivalent isotropic displacement
parameter (ꢁ103) nonhydrogen atoms
Atoms
x
y
z
U(eq)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
5,750(4)
6,197(3)
7,185(3)
6,226(4)
6,781(3)
7,450(3)
7,896(3)
7,708(4)
8,149(4)
8,778(4)
8,977(4)
8,544(4)
7,425(3)
8,030(4)
9,600(5)
10,560(4)
10,021(5)
8,431(4)
7,683(3)
6,640(3)
6,077(3)
6,290(3)
12,118(3)
6,995(1)
4,545(4)
3,266(3)
851(3)
2,748(3)
1,627(3)
48(3)
1,606(1)
1,223(1)
787(1)
57(1)
52(1)
49(1)
63(1)
45(1)
46(1)
48(1)
58(1)
67(1)
67(1)
71(1)
62(1)
51(1)
64(1)
80(1)
83(1)
80(1)
67(1)
51(1)
46(1)
51(1)
80(1)
132(1)
59(1)
ꢂ431(1)
ꢂ31(1)
6(1)
ꢂ1,143(3)
ꢂ838(4)
ꢂ2,015(4)
ꢂ3,488(4)
ꢂ3,803(4)
ꢂ2,651(3)
5,441(3)
6,742(3)
7,530(4)
6,987(5)
5,705(5)
4,940(4)
ꢂ419(2)
2,099(2)
3,486(2)
2,571(2)
7,741(3)
1,370(1)
ꢂ394(1)
ꢂ925(1)
ꢂ1,282(1)
ꢂ1,119(1)
ꢂ603(1)
ꢂ240(1)
1,791(1)
1,512(1)
1,656(2)
2,081(2)
2,371(1)
2,224(1)
520(1)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
N(1)
N(2)
N(3)
O(1)
F(1)
485(1)
721(1)
ꢂ898(1)
2,228(1)
1,431(1)
S(1)

Crystal Structure
145
160.1, 164.0, 192.6. Anal. calcd. for C18H12FN3OS: C, 64.09; H, 3.56; N, 12.46;
Found: C, 64.13; H, 3.49; N, 12.42%.
Crystal Structure Determination
The X-ray diffraction data were collected on a Bruker Smart CCD Area Detector
System (I.I.Sc, Bangalore). Intensity data were collected up to a maximum of
28.37ꢀ for the compound in the x–a scan mode. The data were reduced using
SAINTPLUS [16]. A total of 10,140 reflections were collected, resulting in 3,876
independent reflections, of which the number of reflections satisfying I > 2 r(I) cri-
teria was 2,017. These were treated as observed. The structure was solved by direct
methods and difference Fourier synthesis using SHELXS97 [17]. The positions of all
nonhydrogen atoms were included in the full-matrix least-square refinement using
SHELXL97 [18]. Anisotropic refinement using full-matrix least-square procedures
was carried out for a few cycles until convergence was reached. Then the hydrogen
atoms were fixed geometrically. The R factor after final convergence was 0.0559 and
the maximum and minimum values of residual electron density were 0.307 and ꢂ
0.215 eAꢂ3. Molecular diagrams were generated using ORTEP [19]. The mean plane
˚
calculation was done using the program PARST [20].
Table 3. Anisotropic displacement parameters (ꢁ104) of non hydrogen atoms
Atoms
U11
U22
U33
U23
U13
U12
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
54(2)
48(1)
45(1)
78(2)
42(1)
39(1)
38(1)
55(2)
64(2)
56(2)
71(2)
63(2)
60(2)
73(2)
83(2)
68(2)
81(2)
83(2)
54(1)
49(1)
51(1)
114(2)
98(2)
70(1)
60(2)
52(2)
50(2)
52(2)
49(2)
48(1)
51(2)
57(2)
76(2)
73(2)
61(2)
60(2)
49(2)
54(2)
60(2)
92(3)
103(3)
75(2)
47(1)
40(1)
45(1)
71(1)
150(2)
59(1)
56(2)
56(2)
51(2)
58(2)
46(2)
50(2)
54(2)
61(2)
62(2)
73(2)
80(2)
60(2)
45(2)
64(2)
95(3)
89(3)
55(2)
42(2)
53(1)
49(1)
56(1)
54(1)
148(2)
49(1)
ꢂ2(1)
2(1)
10(1)
6(1)
4(1)
2(1)
0(1)
1(1)
ꢂ12(2)
ꢂ19(2)
ꢂ4(2)
0(2)
6(1)
2(1)
2(1)
ꢂ3(1)
2(2)
ꢂ1(1)
ꢂ2(1)
7(1)
ꢂ5(1)
ꢂ5(1)
ꢂ5(1)
ꢂ4(1)
ꢂ2(2)
7(1)
1(1)
ꢂ1(1)
ꢂ2(1)
1(1)
C(9)
ꢂ1(1)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
N(1)
N(2)
N(3)
O(1)
F(1)
0(2)
ꢂ3(2)
ꢂ6(2)
6(1)
2(2)
9(2)
15(2)
8(1)
7(1)
ꢂ4(1)
4(1)
4(1)
ꢂ5(2)
ꢂ37(2)
ꢂ19(2)
1(1)
1(1)
4(1)
ꢂ1(1)
12(1)
ꢂ49(2)
5(1)
ꢂ12(2)
15(2)
6(2)
1(2)
ꢂ13(2)
4(1)
ꢂ2(2)
ꢂ1(1)
1(1)
0(1)
1(1)
1(1)
1(1)
0(1)
ꢂ14(1)
23(1)
ꢂ45(2)
5(1)
S(1)
ꢂ1(1)

146
A. Banu et al.
Results and Discussion
The Details of crystal data and refinements are given in Table 1. Table 2 gives the list
of atomic coordinates and equivalent isotropic displacement parameters of the non-
hydrogen atoms. Table 3 gives the list of anisotropic displacement parameters of the
nonhydrogen atoms. The bond lengths and bond angles of all the nonhydrogen
atoms are given in Tables 4 and 5. The selected torsion angles are listed in Table 6.
All nonbonded interactions are tabulated in Table 7. The ORTEP diagram of the
molecule with thermal ellipsoids drawn at 50% probability is shown in Fig. 1.
Figures 2, 3, and 4 show the packing of molecules in the crystal structure.
The imidazothiadiazole and aryl ring are planar with a dihedral angle of
0.942(3)ꢀ between them. The fluoro benzyl ring is inclined at an angle of 74ꢀ to these
imidazothiadiazole and aryl ring systems. The carbaldehyde group is coplanar with
an imidazothiadiazole ring and cis to the phenyl ring and the fluoro group is copla-
nar with the benzyl ring. The carbonyl group has a cis orientation with respect to
the C5¼C6 double bond, which leads to a strong intramolecular hydrogen bond.
˚
Table 4. Bond lengths [A]
Atoms
Lengths
S(1)-C(3)
S(1)-C(2)
1.720(3)
1.757(3)
1.349(3)
1.371(3)
1.391(3)
1.305(3)
1.317(3)
1.385(3)
1.401(3)
1.471(3)
1.438(4)
1.392(4)
1.393(4)
1.386(4)
1.491(4)
1.214(3)
1.377(4)
1.386(3)
1.513(4)
1.381(4)
1.382(4)
1.376(4)
1.357(4)
1.369(4)
1.365(5)
1.358(3)
1.365(5)
N(2)-C(3)
N(2)-N(3)
N(2)-C(5)
N(3)-C(2)
N(1)-C(3)
N(1)-C(6)
C(6)-C(5)
C(6)-C(7)
C(5)-C(4)
C(7)-C(8)
C(7)-C(12)
C(8)-C(9)
C(2)-C(1)
O(1)-C(4)
C(13)-C(14)
C(13)-C(18)
C(13)-C(1)
C(12)-C(11)
C(18)-C(17)
C(14)-C(15)
C(10)-C(11)
C(10)-C(9)
C(17)-C(16)
C(16)-F(1)
C(16)-C(15)

Crystal Structure
147
Table 5. Bond angles [ꢀ]
Atoms
Angles
C(3)-S(1)-C(2)
C(3)-N(2)-N(3)
C(3)-N(2)-C(5)
N(3)-N(2)-C(5)
C(2)-N(3)-N(2)
C(3)-N(1)-C(6)
N(1)-C(6)-C(5)
N(1)-C(6)-C(7)
N(2)-C(5)-C(6)
N(2)-C(5)-C(4)
N(1)-C(3)-N(2)
N(1)-C(3)-S(1)
N(2)-C(3)-S(1)
N(3)-C(2)-C(1)
N(3)-C(2)-S(1)
C(1)-C(2)-S(1)
O(1)-C(4)-C(5)
O(1)-C(4)-H(4)
F(1)-C(16)-C(17)
F(1)-C(16)-C(15)
88.11(12)
118.5(2)
107.8(2)
133.71(19)
108.0(2)
104.3(2)
111.1(2)
117.2(2)
103.57(19)
118.2(2)
113.3(2)
137.3(2)
109.42(19)
123.0(2)
116.00(19)
120.9(2)
127.7(3)
116.1
117.9(4)
119.4(4)
=
The C-N bond length in the imidazole ring are longer than that of a typical C N
bond but shorter than that of a C-N bond, indicating electron delocalization in
the ring.
Table 6. Selected Torsion angles (ꢀ)
C(5)-N(2)-N(3)-C(2)
C(3)-N(1)-C(6)-C(7)
N(3)-N(2)-C(5)-C(6)
C(3)-N(2)-C(5)-C(4)
C(7)-C(6)-C(5)-N(2)
N(1)-C(6)-C(5)-C(4)
C(6)-N(1)-C(3)-S(1)
N(3)-N(2)-C(3)-N(1)
C(5)-N(2)-C(3)-S(1)
C(2)-S(1)-C(3)-N(1)
N(1)-C(6)-C(7)-C(8)
N(2)-N(3)-C(2)-C(1)
C(3)-S(1)-C(2)-C(1)
N(3)-C(2)-C(1)-C(13)
S(1)-C(2)-C(1)-C(13)
N(2)-C(5)-C(4)-O(1)
C(18)-C(17)-C(16)-F(1)
F(1)-C(16)-C(15)-C(14)
179.0(2)
ꢂ179.76(19)
ꢂ179.8(2)
178.4(2)
179.6(2)
ꢂ177.7(3)
179.0(2)
179.57(19)
ꢂ178.97(15)
ꢂ179.1(3)
179.3(2)
178.0(2)
ꢂ177.8(2)
95.7(3)
82.2(3)
178.0(3)
179.7(3)
179.6(3)

148
A. Banu et al.
ꢀ
˚
Table 7. Nonbonded interactions and possible hydrogen bonds (A, )
D—H ꢄ ꢄ ꢄ A
D—H
H ꢄ ꢄ ꢄ A
D ꢄ ꢄ ꢄ A
D—H ꢄ ꢄ ꢄ A
C8-H8 . . . O1
0.954(1)
0.930(3)
1.023(5)
0.930(3)
1.023(5)
0.930(3)
2.127(1)
2.755(2)
2.389(5)
2.827(2)
2.827(2)
2.715(2)
3.016(4)
3.477(4)
3.340(4)
3.577 (4)
3.340(4)
3.388(4)
154(2)
135(0)
154(2)
138(0)
154(2)
129(0)
C14-H14 . . . N1a
C4-H4 . . . N3b
C14-H14 . . . O1c
C1-H1A . . . O1c
C17-H17 . . . F1d
ax þ y þ 1,þz;
bx þ 1,ꢂy þ 1, ꢂz;
cx þ 1, ꢂy þ 1, ꢂz;
d
ꢂx þ 1=2 þ 2, þy ꢂ1=2, ꢂz þ 1=2.
D ¼ donor; A ¼ acceptor; H ¼ hydrogen.
The thiadiazole moiety displays differences in the bond lengths of the pairs of
bonds C3-N2=C6-N1 and S1-C2=S1-C3 due to the fused imidazole ring as well as
the different groups that are attached on either side of the imidazothiadiazole ring
˚
˚
system. The difference in bond lengths S1-C3 [1.720(3) A] and S1-C2 [1.757(3) A]
indicates that the resonance effect caused by the imidazole ring is stronger than that
caused by the thiadiazole ring. The imidazole and thiadiazole parts show different p
conjugations, due to their fused nature as well as the groups attached to them. This is
evident from the C-N bond length similarities in the imidazole ring (having values
intermediate between those of single and double bonds) compared to the C-S bond
length differences in the thiadiazole ring. As a result, the imidazole part of this imi-
dazothiadiazole system is more resonance stabilized. Additionally, the imidazothia-
diazole entity is generally planar and rigid.
The molecular structure is primarily stabilized by a strong intramolecular
˚
˚
C8-H8 . . . O1 hydrogen bond [C8-H8 ¼ 0.954(1) A, H8 . . . O1 ¼ 2.127(1) A,
ꢀ
˚
C8 . . . O1 ¼ 3.016(4) A and the angle C8-H8 . . . O1 ¼ 154(2) ] leading to the forma-
tion of a pseudo-seven-membered hydrogen-bonded pattern with graph set S(7), thus
locking the molecular conformation and eliminating conformational flexibility.
The crystal structure is stabilized by intermolecular interactions into a three-
dimensional framework structure by the combination of C-H . . . N, C-H . . . O, and
FIGURE 1. ORTEP view of compound 4 showing 50% probability ellipsoids and the atom
numbering scheme. Dotted line indicates intramolecular C8-H8 . . . O1 interaction.

Crystal Structure
149
FIGURE 2. Crystal structure of 4 viewed along the b axis. Dotted lines indicate intermolecu-
lar C-H . . . N interaction.
C-H . . . F. Hydrogen bonds with C-H as donor play a significant role, functional and
structural, contributing to the overall stability of the molecular packing. The frame-
work is composed of two different C-H . . . N interactions; the first is from C14 to its
neighbor N1 linking the molecule in terms of zig-zag, chain-like structure and the
FIGURE 3. Crystal structure of 4 viewed along the b axis. Dotted lines indicate intermolecu-
lar C-H . . . O interaction generating bifurcated bonds.

150
A. Banu et al.
FIGURE 4. Crystal structure of 4 representing two-dimensional sheet-like structure. Dotted
lines indicate intermolecular C-H . . . F interactions.
second C-H . . . N interaction between C4 and N3 form head-to-head dimers corre-
sponding to graph set notation of R22ð10Þ (Fig. 2). There are two different
C-H . . . O interactions; in the first the molecules are linked by paired C-H . . . O
hydrogen bonds into centrosymmetric dimers corresponding to graph set notation
R22ð18Þ and the second generate bifurcated bonds from two donors, C1 and C14,
to the same acceptor, O1 along the b axis (Fig. 3). The C-H . . . F interactions create
self-assembly in terms of a two-dimensional sheet-like structure along the crystallo-
graphic b axis (Fig. 4). The dependence of the strength of the C-H . . . X interaction
on C-H group acidity [21] meant that the selected compounds should have as large a
number of acidic C-H groups as possible [22]. Thus, we concluded on the basis of
Cambridge Structural Database (CSD) and computational studies that the C-F
group does not favor the formation of F . . . F contacts as do the C-Cl, C-Br, and
C-I groups [23]. This difference between F and the other halogens has been noted
in several other studies [24]. The presence of the fluoro substituent on the benzene
ring enhances the acidity of the C-H groups. There are no aromatic p-p stacking
interactions. The supramolecular aggregation in this structure is thus limited to
the C-H . . . N, C-H . . . O, and C-H . . . F intermolecular interactions giving overall
stability to the structure.
Acknowledgment
N.S.B is thankful to the University Grants Commission (UGC), India, for financial
assistance and Department of Science and Technology (DST), India, for data collec-
tion on the CCD facility set up under the IRHPA-DST program.
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