Hydrogen and halogen bonding patterns and π-π aromatic interactions of some 6,7-disubstituted 1,3-benzothiazoles studied by X-ray diffraction and DFT calculations

Article abstract of DOI:10.1016/j.molstruc.2010.04.005

The structures of five 6,7-disubstituted 1,3-benzothiazole (1,3-benzothiazole = bta) derivatives: 6-chloro-7-nitro-bta (3), 6-iodo-7-nitro-bta (5), 6-amino-7-iodo-bta (6), 6-acetylamino-7-iodo-bta (7) and 6-amino-7-bromo-bta (8) are reported and investigated by X-ray crystallography and DFT calculations. The crystal structures of 3 and 5-8 are characterized by: (i) relatively weak C{single bond}H?O/N/Br and N{single bond}H?O/N/S hydrogen bonds, (ii) C{single bond}Cl?O and C{single bond}I?O/N halogen bonds and Br?Br interactions and (iii) π-π interactions. DFT optimized structures of 3, 5, 6 and 8 are in a good agreement with the corresponding X-ray molecular data. Calculated structure of 7 deviates from the experimental geometry because of more favourable intermolecular hydrogen bonding in crystal phase compared to the weak intramolecular hydrogen bond in the gas phase. The molecular electrostatic potential maps were used for predicting possible hydrogen and halogen bonding sites in structures of 3, 5, 6 and 8, and AIM analysis in order to characterize the nature and strength of intermolecular interactions in all of the examined crystal structures. Experimental results agree well with AIM analysis suggesting that the detected hydrogen and halogen bonds are weak and mostly of electrostatic origin.

Full text of DOI:10.1016/j.molstruc.2010.04.005

Journal of Molecular Structure 975 (2010) 115–127
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Hydrogen and halogen bonding patterns and
p–p aromatic interactions of some
6,7-disubstituted 1,3-benzothiazoles studied by X-ray diffraction and DFT
calculations
a
b
a
c
c
ˇ
ˇ
´
´
´
Helena Cicak , Marijana Ðakovic , Zlatko Mihalic , Gordana Pavlovic , Livio Racané ,
c,
*
´
´
Vesna Tralic-Kulenovic
a Laboratory of Organic Chemistry, Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, Zagreb 10000, Croatia
b Laboratory of General and Inorganic Chemistry, Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, Zagreb 10000, Croatia
c Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovic´a 28a, Zagreb 10000, Croatia
a r t i c l e i n f o
a b s t r a c t
Article history:
The structures of five 6,7-disubstituted 1,3-benzothiazole (1,3-benzothiazole = bta) derivatives: 6-chloro-
7-nitro-bta (3), 6-iodo-7-nitro-bta (5), 6-amino-7-iodo-bta (6), 6-acetylamino-7-iodo-bta (7) and 6-
amino-7-bromo-bta (8) are reported and investigated by X-ray crystallography and DFT calculations.
The crystal structures of 3 and 5–8 are characterized by: (i) relatively weak CAHꢀ ꢀ ꢀO/N/Br and
NAHꢀ ꢀ ꢀO/N/S hydrogen bonds, (ii) CAClꢀ ꢀ ꢀO and CAIꢀ ꢀ ꢀO/N halogen bonds and Brꢀ ꢀ ꢀBr interactions and
Received 23 December 2009
Received in revised form 1 April 2010
Accepted 5 April 2010
Available online 11 April 2010
(iii) p–p interactions.
Keywords:
6,7-Disubstituted 1,3-benzothiazoles
Hydrogen and Halogen bonds
DFT optimized structures of 3, 5, 6 and 8 are in a good agreement with the corresponding X-ray molec-
ular data. Calculated structure of 7 deviates from the experimental geometry because of more favourable
intermolecular hydrogen bonding in crystal phase compared to the weak intramolecular hydrogen bond
in the gas phase.
The molecular electrostatic potential maps were used for predicting possible hydrogen and halogen
bonding sites in structures of 3, 5, 6 and 8, and AIM analysis in order to characterize the nature and
strength of intermolecular interactions in all of the examined crystal structures. Experimental results
agree well with AIM analysis suggesting that the detected hydrogen and halogen bonds are weak and
mostly of electrostatic origin.
p–p Interactions
X-ray structure
DFT calculations
AIM analysis
Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction
port CAHꢀ ꢀ ꢀO/N/Br and NAHꢀ ꢀ ꢀO/N/S hydrogen bonds, CAClꢀ ꢀ ꢀO
and CAIꢀ ꢀ ꢀO/N halogen bonds, Brꢀ ꢀ ꢀBr dihalogen interactions and
Benzothiazoles are an important class of compounds currently
attracting considerable interest due to their biological and bio-
physical properties. They exhibit antitumor [1], antimicrobial [2],
and antifungal [3] activities, and can be used as b-amyloid imaging
agents [4]. Variation of substituents on the benzothiazole ring af-
fects their interactions with various potential biological targets.
Functionalization by appropriate substituents is a key step in
designing molecules with predefined properties such as capability
p–p interactions of 6-chloro-7-nitro-bta (3), 6-iodo-7-nitro-bta
(5), 6-amino-7-iodo-bta (6), 6-acetylamino-7-iodo-bta (7), and
6-amino-7-bromo-bta (8) studied by X-ray crystal structure analy-
sis. DFT calculations were also performed for obtaining minimum
energy and determination of possible hydrogen and halogen bond-
ing sites of studied disubstituted benzothiazoles. Criteria based on
the topological analysis of the electron density, AIM, were used in
order to characterize the nature and strength of hydrogen and hal-
ogen bondings.
of hydrogen bonding or
p–p interactions. While strong hydrogen
bonds have been extensively studied so far, non-conventional
hydrogen bonds and halogen interactions, also occurring in these
compounds, constitute rapidly growing area [5–16].
2. Experimental
As a continuation of our recent studies on synthesis [17,18],
antitumor activities [19,20], structural and computational investi-
gations [21–23] of substituted benzothiazoles, in this paper we re-
2.1. Materials and methods
The 1H NMR and the 13C NMR spectra were recorded by a Bruc-
ker Avance DPX-300 (300 MHz and 75.5 MHz, for 1H and 13C,
respectively). Chemical shifts are reported in ppm relative to
* Corresponding author. Tel.: +385 1 3712 566; fax: +385 1 3712 599.
E-mail address: vtralic@ttf.hr (V. Tralic´-Kulenovic´).
0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.04.005

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
116
TMS as an internal standard. IR spectra were recorded by Nicolet
giving pure product (4.4 g, 68.2%, m.p. = 140–141 °C). Elemental
analysis: Calcd. (found) for C7H3ClN2O2S; C, 39.17 (39.03); H,
1.41 (1.50); N, 13.05 (13.07). 1H NMR (DMSO-d6, 300 MHz), d:
9.58 (s, 1H), 8.39 (d, 1H, J = 8.6 Hz), 7.88 (d, 1H, J = 8.6 Hz). 13C
NMR (DMSO-d6, 75 MHz), d: 161.5, 153.7, 140.5, 132.4, 130.9,
129.5, 126.6. IR (KBr): 3087, 3063, 1592, 1512, 1333, 1304, 848,
822.
Magna 760 spectrophotometer. Elemental analyses were per-
-
´
formed by the microanalytical laboratories of the Ruder Boškovic
Institute. Melting points were determined by a Kofler block
apparatus.
2.2. Preparative and crystallization procedures
6-Amino-bta (1) and 6-chloro-bta (2) were prepared as reported
previously [24]. Compounds 4–8 were synthesized using analo-
gous procedures given in the literature [25]. The novel 6-chloro-
7-nitro-bta (3) was prepared from compound 2 by nitration reac-
tion with a mixture of fuming nitric acid and sulphuric acid
(Scheme 1).
Crystals of 6-chloro-7-nitro-bta (3) were prepared by recrystal-
lization from ethanol; 6-iodo-7-nitro-bta (5) by recrystalization
from mixture of toluene/cyclohexane (1:1); 6-amino-7-iodo-bta
(6) by recrystallization from toluene/petrolether (5:1); 6-acetyl-
amino-7-iodo-bta (7) by recrystallization from ethanol/dichlorme-
thane (1:2); 6-amino-7-bromo-bta (8) from ethanolic solution by
slow evaporation at room temperature.
2.4. X-ray single crystal diffraction experiment
Selected crystallographic and refinement data for structures 3,
5–8 obtained by the single crystal X-ray diffraction method are re-
ported in Table 1. Data collections were carried out on an Oxford
Diffraction four-circle kappa geometry diffractometer with Sap-
phire-3 CCD detector (Mo radiation with graphite monochromator)
by applying the CrysAlis software system [26] at 296 K. The unit
cell parameters were calculated and refined from the full data
set, the Lorentz-polarization effect was corrected and the intensity
data reduced by the CrysAlis RED program [26]. The diffraction
data were corrected for absorption effects by the multi-scanning
method. All structures were solved by direct methods and refined
on F2 by weighted full-matrix least-squares. Programs SHELXS97
and SHELXL97 [27] integrated in the WinGX software system
[28] were used to solve and refine all five structures. All non-
hydrogen atoms were refined anisotropically. The H atoms of ami-
no groups in 6 and 8 were located in Fourier difference map and
constrained to an ideal geometry [NAH = 0.86 Å], while in 7, H
atom attached to the amine N atom was placed in geometrically
idealized position. All other hydrogen atoms were included in the
refinement at calculated positions in the riding-model approxima-
2.3. 6-Chloro-7-nitro-bta (3)
To a cooled mixture of 6-chloro-bta (2) (5.1 g, 30 mmol) in
20 mL of concd. H2SO4 a mixture of 10 mL HNO3 (d = 1.5) and con-
cd. H2SO4 was added dropwise at 5–10 °C. The reaction mixture
was stirred for 3 h at room temperature, poured into cold water
and basified with concd. ammonia. The resulting precipitate was
filtered off, washed with water and crystallized from ethanol
Scheme 1. Synthesis of compounds 3, 5–8.

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
117
Table 1
General and crystal data and summary of intensity data collection and structure refinement for compounds 3, 5–8.
Compound
3
5
6
7
8
Formula
Mr
C7H3ClN2O2S
214.63
C7 H3IN2O2S
306.08
C7H5IN2S
276.1
C9H7IN2OS
318.14
C7H5BrN2S
229.1
Crystal system
Colour and habit
Space group
Crystal dimensions (mm3)
Unit cell parameters:
a (Å)
Monoclinic
Dark yellow, prism
P21/c
0.62 ꢁ 0.34 ꢁ 0.22
Monoclinic
Yellow, prism
P21
0.47 ꢁ 0.39 ꢁ 0.32
Orthorhombic
Yellow–reddish, prism
P212121
0.61 ꢁ 0.54 ꢁ 0.37
Monoclinic
Pale yellow, plate
P21
0.62 ꢁ 0.44 ꢁ 0.13
Orthorhombic
Colourless, irregular prism
I 41/a
0.53 ꢁ 0.49 ꢁ 0.45
3.8851(7)
13.737(2)
15.263(3)
90
4.1437(7)
12.948(2)
16.747(2)
90
4.1698(5)
13.454(1)
14.9533(8)
90
4.7726(5)
6.7351(6)
16.2194(14)
90
19.526(2)
19.526(2)
8.1404(8)
90
b (Å)
c (Å)
a
(°)
b (°)
96.16(1)
90
809.9(2)
4
1.76
0.69
91.661(12)
90
898.1(2)
4
2.264
3.763
90
90
90.973(7)
90
521.28(8)
2
2.027
3.239
90
90
3103.7(5)
16
1.961
c
(°)
V (Å3)
838.88(13)
4
2.186
3.998
Z
Dc (g cmꢂ3
)
l
(mmꢂ1
)
5.493
F(0 0 0)
432
576
520
304
1792
2h range for data collection (°)
h, k, l range
Scan type
8, 54
8, 54
8, 54
8, 54
8, 54
ꢂ4:4, ꢂ17:17, ꢂ19:19
ꢂ5:5, ꢂ16:16, ꢂ21:20
ꢂ5:5, ꢂ17:17, ꢂ19:19
ꢂ6:6, ꢂ8:8, ꢂ20:20
ꢂ24:24, ꢂ24:24, ꢂ10:10
x
x
x
x and u
x
No. measured reflections
No. independent reflections (Rint
No. refined parameters
9229
1751 (0.117)
118
11,114
3852 (0.067)
235
7673
1791 (0.051)
101
6459
2165(0.083)
128
17,738
1695(0.154)
101
)
No. observed reflections, I P 2
r(I)
1610
3601
1787
2143
1677
g1, g2 in wa
0.0652, 0.6021
0.0486, 0.1230
0.0587, 0.1271
1.045
0.0718, 1.1408
0.0450, 0.1191
0.0476, 0.1230
1.062
0.0535, 0.9038
0.0297, 0.0831
0.0297, 0.0832
1.085
0.1072, 0.0258
0.0511, 0.1321
0.0514, 0.1329
1.105
0.0325, 10.9442
0.0468, 0.1104
0.0480, 0.1109
1.151
Rb, wRc [I P 2
r(I)]
R, wR [all data]
Goodness of fit on F2, Sd
Extinction coefficient
none
none
0.006(1)
0.754, ꢂ1.109
0.001
none
0.0014(2)
0.830, ꢂ0.508
0.000
e
Max., min. electron density (e Åꢂ3
)
0.681, ꢂ0.850
0.873, ꢂ1.219
1.443, ꢂ1.577
Maximum
D/r
0.000
0.000
0.000
Data in common: diffractometer used for data collection: CrysAlis, Version 171.23 (Oxford Diffraction, 2004) with k(Mo K
a
) = 0.71073 Å at 296 K.
h
i
ꢀ
ꢁ
w ¼ 1= r2ðF2oÞ þ ½g1P þ g2Pꢃ where P ¼ Fo2 þ 2F2c =3.
a
b
c
P
P
P
R = |Fo–Fc|/ |Fo|.
P
P
2
2 1=2
wR ¼ ½ ðF2o ꢂ Fc2Þ = wðF2oÞ ꢃ
.
h
i
1=2.2
2
wðF2o ꢂ Fc2Þ =ðNobs ꢂ Nparam
Þ
d
e
S ¼
In structures 5, 7 and 8 the max. electron density in the last difference Fourier map is near halogen atoms, in 3 near O2 and in 6 near C5 and I1 atoms 0.75 and 0.72 e Å3,
respectively).
tion, with Csp2AH and Csp3AH distances of 0.93 and 0.96 Å,
respectively. The Uiso(H) amounts 1.2 of Ueq(C) or Ueq(N) in all
cases, except for hydrogen of methyl group [Uiso(H) = 1.5 of Ueq(C)].
The absolute structure of 5, 6 and 7 has been established by the
Flack’s parameters values, which are all zero within the standard
uncertainties.
The molecular geometry calculations and drawings were per-
formed by PLATON [29], ORTEP-3 for Windows [30] and Mercury
[31]. The thermal ellipsoids are drawn at the 50% probability level
at 293 K. The Ortep drawings are shown on Figs. 1A–5A.
gram [35] by aligning equivalent atoms in superimposed
structures and calculating the root-mean-square deviation (RMSD)
and the maximum difference between superimposed atoms.
Values of molecular electrostatic potential (MEP) were calcu-
lated at isodensity surface of contour value 0.0007 a.u. of previ-
ously optimized structures in order to find regions of positive
and negative MEP and hence to predict possible sites capable of
electrostatic interactions. Negative MEP (electron-rich) regions
are coloured red, positive MEP (electron-poor) regions are blue,
and zero MEP regions are green. Value of the MEP is given by the
intensity of colour. The MEP maps were visualized by GaussView
program [36]. The hydrogen and halogen bonding characteristics
of the studied crystal structures have been investigated by the Bad-
er’s theory of ‘‘Atoms in Molecules” (AIM) [37–39]. The wave func-
tions were obtained by single point calculations at the
abovementioned level of theory for neighbouring molecules con-
taining short contact(s) at the geometry taken from the crystal
structure. The bond critical points (BCPs) were found and analyzed
in terms of the electron density, its Laplacian and the electron en-
ergy density. The topological analysis was performed with the help
of AIM2000 [40] and AIMAll [41] programs.
2.5. Computational methods
Density functional theory (DFT) calculations were carried out
with the Gaussian 03 program [32]. B3LYP hybrid method, which
uses Becke’s three-parameter exchange functional and gradient-
corrected correlation functional of Lee, Yang and Parr [33], was em-
ployed to predict the minimum energy molecular geometries of
five 6,7-disubstituted btas 3, 5–8. The geometries were fully opti-
mized in the gas phase with tight convergence criteria using Pople
valence triple zeta 6-311+G(d,p) basis set for all the atoms except
iodine, for which it does not exist. Therefore 6-311G(d,p) basis set
was used for iodine [34]. The harmonic vibrational analysis was
performed at the same level of theory in order to verify that all
of the vibrational frequencies were real, confirming the structure
as minimum.
3. Results and discussion
3.1. Crystal structures description
Comparison of the computational results and the experimen-
tally determined structures was performed with Maestro 9.0 pro-
A survey of the Cambridge Structural Data base (CSD) con-
ducted on version 5.30 (including update 4, September 2009)

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
118
Table 2
Selected bond distances (Å).
Compound (3)
Compound (5)
X-ray
Compound (6)
X-ray
Compound (7)
X-ray
Compound (8)
X-ray
X-ray
Calc
Calc
Calc
Calc
Calc
S1AC1
S1AC2
N1AC1
N1AC7
C2AC3
C2AC7
C3AC4
C4AC5
C5AC6
C6AC7
1.739(3)
1.762
1.744
1.289
1.383
1.407
1.413
1.401
1.404
1.383
1.398
S11AC11
S21AC21
S11AC12
S21AC22
N11AC11
N21AC21
N11AC17
N21AC27
C12AC13
C22AC23
C12AC17
C22AC27
C13AC14
C23AC24
C14AC15
C24AC25
C15AC16
C25AC26
C16AC17
C26AC27
1.74(1)
1.73(1)
1.701(8)
1.727(8)
1.30(1)
1.26(1)
1.39(1)
1.40(1)
1.44(1)
1.40(1)
1.40(1)
1.39(1)
1.37(1)
1.39(1)
1.38(1)
1.42(1)
1.39(1)
1.36(1)
1.38(1)
1.40(1)
1.761
S1AC1
S1AC2
N1AC1
N1AC7
C2AC3
C2AC7
C3AC4
C4AC5
C5AC6
C6AC7
1.733(5)
1.735(4)
1.286(7)
1.373(6)
1.383(7)
1.411(6)
1.402(6)
1.408(7)
1.371(7)
1.394(7)
1.768
S1AC1
S1AC2
N1AC1
N1AC7
C2AC3
C2AC7
C3AC4
C4AC5
C5AC6
C6AC7
1.744(7)
1.721(5)
1.247(9)
1.403(9)
1.380(8)
1.390(8)
1.394(8)
1.385(9)
1.40(1)
1.767
S1AC1
S1AC2
N1AC1
N1AC7
C2AC3
C2AC7
C3AC4
C4AC5
C5AC6
C6AC7
1.740(5)
1.726(4)
1.276(6)
1.397(5)
1.389(5)
1.397(5)
1.390(5)
1.404(5)
1.374(5)
1.379(6)
1.769
1.722(2)
1.286(4)
1.392(3)
1.404(3)
1.401(3)
1.396(3)
1.398(3)
1.372(4)
1.393(3)
1.745
1.290
1.383
1.406
1.413
1.401
1.406
1.384
1.397
1.749
1.287
1.385
1.397
1.414
1.403
1.418
1.379
1.400
1.750
1.287
1.385
1.394
1.415
1.406
1.415
1.382
1.397
1.747
1.287
1.385
1.394
1.413
1.401
1.417
1.380
1.401
1.375(9)
C8AC9
I1AC3
1.502(9)
2.079(6)
1.519
2.139
Cl1AC4
O1AN2
1.722(2)
1.221(3)
1.741
1.230
I11AC14
I21AC24
O11AN12
O21AN22
2.108(8)
2.088(7)
1.22(1)
1.12(1)
2.127
1.230
I1AC3
2.099(4)
2.132
Br1AC3
1.886(4)
1.918
O1AC8
1.231(7)
1.216
O2AN2
N2AC3
1.213(3)
1.460(3)
1.219
1.472
O12AN12
O22AN22
N12AC13
N22AC23
1.16(1)
1.21(1)
1.46(1)
1.47(1)
1.220
1.473
N2AC4
1.388(6)
N2AC4
N2AC8
1.437(8)
1.329(8)
1.404
1.384
N2AC4
1.398(5)
1.385
Fig. 1B. Crystal packing of 3 determined mainly by CAClꢀ ꢀ ꢀO halogen bonds which
are presented by dashed lines.
plane. In the structures of nitro and acetylamino derivatives, 3 and
5, and 7, respectively, the planes containing NO2 and the acetyl-
amino group are turned out of the bta planes to which they are at-
tached [the dihedral angles amount 14.9(2)° (3) and 8(1)° (5) (in
both molecules) for NO2 groups, and 51.9(3)° (7) for acetylamino
group]. For the halide atoms, the largest deviation is expectedly ob-
served for iodine. The iodine atoms are found to be out of the bta
planes in the range from 0.095(8) Å in (5) to 0.142(5) Å in (6).
Moreover, the observed deviations are in a good correlation with
the substituents present in the neighbouring positions and their
flexibility to minimize steric repulsions.
Fig. 1A. The ORTEP drawing of 6-chloro-7-nitro-bta (3) with the atom numbering
scheme of the asymmetric unit.
[42] using ConQuest [43] (version 1.8) has revealed a total of only
four entries that contain bta fragment having one or two substitu-
ents in positions 6 and/or 7. Structurally are characterized one
disubstituted, 7,70-dinitro-6,60-bi-bta [25] and three monosubsti-
tuted bta, all with substituent only in position 6: 6-iodo-bta [25],
bta-6-carboxamidinium chloride dihydrate [21] and 2-(1,3-ben-
zothiazol-6-yl)-4,5-dihydro-1H-imidazol-3-ium chloride [18]. To
the best of our knowledge, apart from 7,70-dinitro-6,60-bi-bta
[25], the five structures reported in this paper are the first structur-
ally characterized 6,7-disubstituted btas.
In all structures, 3, 5–8, the two SAC bonds of the thiazole rings
[e.g. S1AC1 and S1AC2 in 3, 6–8, as well as S11AC11, S11AC12 and
S21AC21, S21AC22 in 5] differ with respect to each other, but both
are within two border cases, single SAC [1.82 Å] and double S@C
In all five structures, 3, 5–8, the bta moiety is found to be
expectedly planar, but all substituents deviate somewhat from that

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
119
Fig. 2A. The ORTEP drawing of 6-iodo-7-nitro-bta (5) with atom numbering scheme of the asymmetric unit.
Fig. 2B. Perspective view of crystal packing of 5. Hydrogen and halogen bonds are shown by dashed lines.
[1.56 Å] bond [44], while the CAN endocyclic bond within the thi-
azole fragment is dominantly double in character C1AN1
1.285(4) Å in 3, 1.30(1) and 1.26(1) Å in 5, 1.288(7) Å in 6,
1.247(9) Å in 7 and 1.277(6) Å in 8] [45] (Table 2). The bond angles
around the S atom are within the range found in the five-mem-
bered thiazole rings of reported mono- and disubstituted bta and
its derivatives [18,21,25]. The differences in the CAC bonds within
benzene ring are common for such fused rings.
In the crystal structure of 3 the hydrogen bonding intermolecu-
lar interactions are not well pronounced, only some very weak
ones, far above the 3.5 Å limit are observed. The crystal packing
is mainly determined by CAClꢀ ꢀ ꢀO halogen–nitro bonds. Two such
bonds are formed between two neighbouring molecules creating
double
halogen
bonded
centrosymmetrical
dimmers
[Cl1ꢀ ꢀ ꢀO2 = 3.104(3) Å] (Fig. 1B). The chlorine–oxygen contact is
well below the sum of van der Waals radii (3.3 Å). The observed
interaction is in accordance with the results given by Allen et al.
[50]. They studied geometrical preferences of halogenꢀ ꢀ ꢀO(nitro)
supramolecular synthons and found that for chlorine there is a
strong tendency to form interactions with only one oxygen atom
of nitro group, rather than bifurcated contacts with both oxygens.
The latter arrangement is typical for iodine and to some extent for
bromine, e.g. the tendency to form such bifurcated motifs increases
The crystal structures 3 and 5–8 are determined by three fac-
tors: (i) relatively weak CAHꢀ ꢀ ꢀO/N/Br and NAHꢀ ꢀ ꢀO/N/S hydrogen
bonds, (ii) CAClꢀ ꢀ ꢀO and CAIꢀ ꢀ ꢀO/N halogen bonds and Brꢀ ꢀ ꢀBr
interactions, and (iii)
p–p interactions [46–49]. The pertinent
structural parameters of hydrogen- and halogen-bonded contacts
are collected in Table 3, while the details of
ven in Table 4.
p–p geometries are gi-

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120
addition, both iodine atoms, I11 and I21, are found to be involved
into halogen bonding with oxygen atom of nitro group, O11
[I11ꢀ ꢀ ꢀO11 = 3.11(1) Å], and the thiazole ring nitrogen atom, N11
[I21ꢀ ꢀ ꢀN11 = 3.044(8) Å], both belonging to the first molecule. The
substitution of chlorine atom in 3 with iodine atom in 5 did not
give the typical bifurcated contacts of iodine atom with both oxy-
gen atoms of nitro group [50]. Furthermore, the molecules are
additionally stabilized by the p–p stacking interactions established
between the thiazole and benzene rings in [1 0 0] direction.
The hydrogen bonding interactions are in the crystal structure
of compound 6 not well pronounced. The supramolecular structure
is dominated by weak NAHꢀ ꢀ ꢀS and CAHꢀ ꢀ ꢀN hydrogen bonds
(Fig. 3B). The former interaction, found between the amine group
hydrogen atoms and the thiazole sulphur atom, forms the endless
C(6) zig-zag chains in [0 1 0] direction [51,52], while the latter one,
observed between the thiazole carbon and nitrogen atoms of two
Fig. 3A. The ORTEP drawing of 6-amino-7-iodo-bta (6) with atom numbering
scheme of the asymmetric unit.
in the order Cl < Br < I. Furthermore, the molecules are packed in
such way that bta planes of supramolecular dimers are in stacks
along [1 0 0] direction with the distance between the centroids of
their thiazole and benzothiazole rings of 3.723(2) Å.
Distinctly to all other described compounds, the crystal struc-
ture of compound 5 contains two symmetrically independent mol-
ecules. Consequently, different kinds of intermolecular interactions
are observed involving these two molecules (Fig. 2B). The carbon
atoms of the thiazole rings, C11 and C21, as well as the carbon
atoms of the benzene rings, C15 and C25, of both molecules all
act as hydrogen bond donors for weak CAHꢀ ꢀ ꢀN and CAHꢀ ꢀ ꢀO
hydrogen bondings with the thiazole nitrogen and nitro oxygen
atoms forming three-dimensional supramolecular structure. In
Fig. 4A. The ORTEP drawing of 6-acetylamino-7-iodo-bta (7) with atom numbering
scheme of the asymmetric unit.
Fig. 3B. Crystal packing of 6 shown down the a axis. Hydrogen and halogen bonds are presented by dashed lines.

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
121
h
i
Fig. 4B. Packing diagram of 7, showing NAHꢀ ꢀ ꢀO, CAHꢀ ꢀ ꢀO hydrogen and CAIꢀ ꢀ ꢀN halogen interactions as dashed lines. The hydrogen bonds forms Cð4Þ R12ð6Þ chains in
[1 0 0] direction.
neighbouring molecules, forms C(3) zig-zag chains in [1 0 0] direc-
tion. Interestingly, the thiazole nitrogen atom additionally acts as
acceptor for one more interaction, this time it accepts iodine as
well, forming short Iꢀ ꢀ ꢀN contact of 3.206(5) Å, well below the
sum of van der Waals radii (3.5 Å). Moreover, there exist one more
weak hydrogen bonding interaction in [1 0 0] direction involving
donating benzene ring carbon atom C5 and accepting amine nitro-
gen atom N2. This interaction forms helical C(4) chains. Further-
more, the molecules are also in stacks in [1 0 0] direction with
the distance between the centroids of their thiazole and benzene
rings of 3.819(3) Å, resulting in similar stacking interactions as ob-
served in structures 3 and 5.
The supramolecular structure of compound 7 contains stronger
NAHꢀ ꢀ ꢀO hydrogen bonds utilizing the acetylamino N and O atom
of adjacent molecules forming amide C(4) chains (Fig. 4B). Addi-
tionally, the methyl carbon atom C9 is involved into weak hydro-
gen bonding interaction with the same accepting atom O1. The
two described interactions form the chains of molecules in
[1 0 0] direction that could be described by graph-set notation of
h
i
Cð4Þ R12ð6Þ . These chains are further organized into two-dimen-
Fig. 5B. A partial packing diagram of 8, representing the R44ð8Þ motif formed
between the amino groups of four neighbouring molecules. Hydrogen bonds are
shown by black dashed lines.
Fig. 5A. The ORTEP drawing of 6-amino-7-bromo-bta (8) with atom numbering
scheme of the asymmetric unit.

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
122
sional supramolecular sheets in (1 0 0) planes by C3AI1ꢀ ꢀ ꢀN1 halo-
gen bonds [Iꢀ ꢀ ꢀN = 3.027(6) Å]. The crystal structure of 7 is the only
3.6683(3) Å are found in 8 that are comparable with the sum of
van der Waals radii (3.7 Å [53]; 3.9 Å [54]). The off-set stacking
interactions are found in the structure of compound 8 as well,
but this time between the thiazole and benzene rings with the dis-
tance between centroids of 3.894(2) Å.
one of the described in this paper where
observed.
p–p interactions are not
The crystal structure of 8, presented on Fig. 5B, is dominated by
two moderately weak NAHꢀ ꢀ ꢀN hydrogen bonds. The hydrogen
bonding between two amino groups of four neighbouring mole-
cules forms interesting hydrogen bonding ring structure described
by R44ð8Þ graph-set notation. While one hydrogen atom of amino
group is accepted by amino group nitrogen atom, N2, the other
one is accepted by the thiazole nitrogen atom, N1. The later inter-
action form discrete D(3) graph-set motifs. These two interactions
form three-dimensional supramolecular structure. Interestingly,
the bromine atom is not involved into halogen bonding with the
thiazole nitrogen atom as it is already involved into significantly
stronger NAHꢀ ꢀ ꢀN hydrogen bonding. Consequently, the bromine
acts as the hydrogen bonding acceptor in weak C1AH1ꢀ ꢀ ꢀBr1
hydrogen bond. Additionally, the short Brꢀ ꢀ ꢀBr contact of
Scheme 2. The bta moiety without any substituents and hydrogen atoms.
Table 3
Hydrogen and halogen bonds geometry (Å, °) for compounds 3, 5–8.
DAH/Xꢀ ꢀ ꢀA
DAH/X
H/Xꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
\DAH/Xꢀ ꢀ ꢀA
Symmetry code
Compound 3
C4ACl1ꢀ ꢀ ꢀO2
1.722(4)
3.104(3)
4.821(4)
174.2(1)
ꢂx, 1ꢂy, ꢂz
Compound 5
C11AH11ꢀ ꢀ ꢀN21
C21AH21ꢀ ꢀ ꢀO12
C15AH15ꢀ ꢀ ꢀO21
C25AH25ꢀ ꢀ ꢀO21
C14AI11ꢀ ꢀ ꢀO11
C24AI21ꢀ ꢀ ꢀN11
0.93
0.93
0.93
0.93
2.110(8)
2.088(7)
2.52
2.46
2.66
2.54
3.11(1)
3.044(8)
3.43(1)
3.39(2)
3.47(1)
3.42(2)
5.21(1)
5.12(1)
165
171
147.1
157
173.7(3)
170.7(3)
x, y, z
ꢂ3ꢂx, ꢂ1/2 + y, ꢂ2ꢂz
ꢂ2 + x, 1 + y, z
ꢂx, 1/2 + y, ꢂ1ꢂz
ꢂ4ꢂx, 1/2 + y, ꢂ2ꢂz
ꢂ1ꢂx, ꢂ1/2 + y, ꢂ1ꢂz
Compound 6
N2AH22 Nꢀ ꢀ ꢀS1
C1AH1ꢀ ꢀ ꢀN1
C3AI1ꢀ ꢀ ꢀN1
0.86
0.93
2.100(4)
2.80
2.53
3.206(5)
3.501(5)
3.432(6)
5.289(6)
140
163
170.8(1)
2ꢂx, 1/2 + y, ꢂ3/2ꢂz,
ꢂ1/2 + x, ꢂ3/2ꢂy, ꢂ1ꢂz
3/2ꢂx, ꢂ1ꢂy, ꢂ1/2 + z
Compound 7
N2AH2ꢀ ꢀ ꢀO1
C9AH9Bꢀ ꢀ ꢀO1
C3AI1ꢀ ꢀ ꢀN1
0.86
0.96
2.079(6)
2.08
2.54
3.027(6)
2.917(6)
3.219(9)
5.100(8)
164.0
127.8
174.9(2)
ꢂ1 + x, y, z
ꢂ1 + x, y, z
ꢂ1 + x, ꢂ1 + y, z
Compound 8
N2AH12 Nꢀ ꢀ ꢀN1
N2AH22 Nꢀ ꢀ ꢀN2
C1AH1ꢀ ꢀ ꢀBr1
0.88
0.91
0.93
2.510
2.420
2.937
3.285(5)
3.324(5)
3.641(4)
148
170
124
x, y, 1 + z
ꢂ1/4ꢂy, ꢂ1/4 + x, 7/4ꢂz
x, y, zꢂ1
Table 4
Geometrical parameters of
p–p interactions (Å, °) for compounds 3, 5–8.
Interactiona
CgACg distance
3.7231(15)
3.895(5)
Cgꢀ ꢀ ꢀP1b
Cgꢀ ꢀ ꢀP2c
ad
be
(CgACg) ꢁ sin bf
1.279
3
Cg1ACg2i
3.4915(10)
3.697(4)
3.4964(9)
3.681(3)
0.47(11)
0.7(4)
0.3(2)
0
20.10
19.08
21.42
26.53
5
Cg1ACg2i
1.273
6
Cg1ACg2i
3.819(3)
3.562(2)
3.556(2)
1.395
8
Cg1ACg2ii
3.894(2)
3.4838(15)
3.4838(15)
1.739
a
Ring Cg1 is defined by the atoms S1, C1, N1, C7, C2 (thiazole ring atoms) in 3, 6 and 8 and by the atoms C22, C23, C24, C25, C26, C27 (phenyl ring atoms) in 5. Cg2 is
defined by the atoms S1, C1 N1, C7, C6, C5, C4, C3, C2 (benzothiazole ring atoms) in 3, C2, C3, C4, C5, C6, C7 (phenyl ring atoms) in 6 and 8 and by the atoms S21, C21, N21, C27,
C22 (thiazole ring atoms) in 5.
b
Cgꢀ ꢀ ꢀP1 is the perpendicular distance of corresponding centroid to a plane. Planes P1 or P2 are defined by the atoms, which define the corresponding centroids.
c
Cgꢀ ꢀ ꢀP2 is the perpendicular distance of corresponding centroid to a plane. Planes P1 or P2 are defined by the atoms, which define the corresponding centroids.
d
Dihedral angle between P1 and P2.
e
Angle between CgACg distance and Cgꢀ ꢀ ꢀP1.
f
Offset.
i
ꢂ1 + x, y, z.
ii
ꢂx, ꢂy, 1ꢂz.

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123
Table 5
The root-mean-square deviation (RMSD) and the maximum difference (dmax) between superimposed atom positions of the X-ray and calculated molecular structures of 3, 5–8.
Structure
btaa
allb
RMSD (Å)
dmax (Å)
Atom pairc
RMSD (Å)
dmax (Å)
Atom pairc
3
0.016
0.024
0.029
0.022
0.035
0.021
0.027
0.037
0.043
0.033
0.060
0.035
S1AS1
S11AS1
C23AC3
C1AC1
S1AS1
C1AC1
0.087
0.109
0.104
0.039
0.425
0.051
0.222
0.287
0.252
0.083
1.149
0.130
O2AO2
O12AO2
O21AO1
I1AI1
O1AO1
N2AN2
5–1
5–2
6
7
8
a
b
c
Only bta moiety without any substituents and hydrogens.
All non-hydrogen atoms.
Maximum difference superimposed exp-calc atom pair.
Fig. 6. Intramolecular interaction in calculated structure (A) and intermolecular interactions in X-ray structure (B) of compound 7.
3.2. Computational results
slightly depend on the method and the basis set used. Besides good
matching of calculated structures of 3, 5, 6 and 8 with experimen-
tal ones, it is also generally considered that used calculation model
gives geometries which can be reliably used in other molecular
properties calculations.
3.2.1. Molecular structures
In order to verify the accuracy of used theoretical model all of
the investigated molecules were fully optimized in the gas phase
and obtained geometries compared with the experimental ones.
RMSD values between equivalent atom pairs were calculated for:
(1) bta moiety without any substituents and hydrogens (Scheme 2),
and (2) all non-hydrogen atoms (Table 5). First RMSD values are all
smaller than 0.04 Å indicating good matching of bta moieties. Max-
imum differences (dmax) and corresponding equivalent atoms are
given in the next two columns. The dmax values belong to S1exp
and S1calc or C1exp and C1calc atom pairs of thiazole part, except
C23exp and C3calc pair in 5–2. Second RMSD values go up to
0.11 Å for structures 3, 5, 6 and 8, while for 7 it is much larger
(0.425 Å). The dmax values belong to one oxygen atom of nitro
group in 3 and 5, iodine atom in 6, oxygen atom of acetylamino
group in 7 and nitrogen atom of amino group in 8. As a result of
superposition, it can be concluded that four calculated structures
of 3, 5, 6 and 8 are in good agreement with X-ray molecular struc-
tures, while the calculated structure of 7 is not.
The calculated structures of 3, 5, 6 and 8 have no symmetry,
while that of 7 has plane of symmetry (Cs point group). In opti-
mized structure of 7, there is an intramolecular hydrogen bond be-
tween C5AH5ꢀ ꢀ ꢀO1 of 2.15 Å forming six-membered ring (Fig. 6A).
In the X-ray crystal structure of 7 two intermolecular hydrogen
bonds N2AH2ꢀ ꢀ ꢀO1 (2.08 Å) and C9AH9Bꢀ ꢀ ꢀO1 (2.54 Å) are formed
between adjacent molecules also making six-membered R12ð6Þ ring
(Fig. 6B). The reason for that difference is that two hydrogen bonds
observed in solid state are stronger than intermolecular hydrogen
bond obtained by calculation on single molecule in the gas phase.
Except of different environment in theoretical calculation and
X-ray diffraction experiment, it is also known that geometry can
3.2.2. Molecular electrostatic potential maps
The molecular electrostatic potential has been successfully used
for predicting sites participating in electrostatic interactions and
hydrogen bondings [55–57].
Because of the geometric and electronic similarity of molecules
3 and 5, as well as 6 and 8, there are two types of the electrostatic
potential maps, type I and type II, respectively (Fig. 7A). They show
positive MEP regions (blue1 colour) associated with the acidic H
atoms bonded to C1 in thiazole ring and C5 and C6 in benzene ring
in all of the studied compounds, as well as H atoms of NH2 group in
molecules 6 and 8. Negative MEP regions (red colour) are associ-
ated with O1 and O2 atoms in NO2 group in 3 and 5, N2 atom of
NH2 group in 6 and 8 and with N1 and S1 atoms in thiazole ring
and halogen atoms in all studied compounds. All these regions,
or, to be more accurate, atoms associated with them, are capable
of forming hydrogen bonds either as hydrogen donors, DAH (blue
regions), or hydrogen acceptors, A (red regions). They are given in
Table 6. N2 atoms of NO2 group in molecules 3 and 5 are also
positive.
Halogen atom (X) needs special attention because it can act as:
(1) hydrogen (proton) acceptor forming DAHꢀ ꢀ ꢀX hydrogen bond,
which has already been mentioned, (2) electron acceptor forming
short contact with atom containing lone pair (Lewis base), Xꢀ ꢀ ꢀY
(Y = nitrogen, oxygen, etc.) or (3) participant of the halogenꢀ ꢀ ꢀhal-
1
For interpretation of color in Figs. 1–8, the reader is referred to the web version of
this article.

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
124
Fig. 7A. Molecular electrostatic potential maps (isovalue = 0.0007) of 6,7-disubstituted-btas 3 and 5 (type I, MEP range = ꢂ0.005/+0.025 kJ/e) and 6 and 8 (type II, MEP
range = ꢂ0.016/+0.025 kJ/e).
Fig. 7B. Molecular electrostatic potential maps (Isovalue = 0.0007) of 6,7-disubstituted-btas 3 and 5 (type I, MEP range = ꢂ0.005/+0.025 kJ/e) and 6 and 8 (type II, MEP
range = ꢂ0.016/+0.025 kJ/e) – view along the XAC bond axis.
Table 6
δ
Molecular sites capable for hydrogen bonding (DAHꢀ ꢀ ꢀA) obtained by molecular
electrostatic potential maps for structures of 3, 5, 6 and 8 (isovalue is 0.0007 a.u., MEP
range in I is ꢂ0.005/+0.025 kJ/e, in II is ꢂ0.016/+0.025 kJ/e).
C
X δ
3 and 5 (I)
6 and 8 (II)
DAH (blue)
N2AH12 N
N2AH22 N
C1AH1
C5AH5
C6AH6
ꢂ
ꢂ
+
+
+
+
+
+
+
+
Scheme 3. Anisotropically distributed electron density around a bonded halogen
atom.
slightly vary depending on the halogen and abovementioned ef-
fects. As a consequence of multidirectional character of halogen
interactions, there is the possibility of more than one interaction
of single halogen atom, which can be seen in crystal structure 8
(X = Br).
A (red)
O1
O2
N1
+
+
+
+
+
ꢂ
ꢂ
ꢂ
+
+
+
S1
X1*
N2 (NH2 group)
+
*
3.2.3. AIM analysis
X1 is Cl1 in 3, I1 in 5 and 6 and Br1 in 8.
Table 7 tabulates the topological properties (electron density
(qb), Laplacian of electron density (»
2qb), kinetic electron energy
ogen interaction, Xꢀ ꢀ ꢀX0. The essentially electrostatic Xꢀ ꢀ ꢀY or Xꢀ ꢀ ꢀX0
interactions (types 2 and 3) have been called halogen bonds [15].
Theoretical and experimental analyses have shown that the elec-
tron density around a bonded halogen atom is not spherically
but anisotropically distributed: negative charge is concentrated
in the equatorial area (i.e., perpendicular to the CAX axis) and po-
density (Gb), potential electron energy density (Vb), total electron
energy density (Hb = Vb + Gb) and |Vb|/Gb ratio [37–39]) of the BCPs
for the molecules examined in this work. Prior to discussion of the
results, it is important to recall that the sign and magnitude of
value determines a nature and strength of the interaction. When
2qb < 0 and is large in magnitude, the electron density is also
»
2qb
»
sitive charge along the CAX bond, which is called
r
-hole (Scheme
large and locally concentrated in the internuclear region. Such an
3). This effect, known as polar flattening, is strongly enhanced by
the presence of electron withdrawing groups (e.g. nitro in ortho po-
sition in 3 and 5) and also increasing in the order Cl < Br < I.
From the electrostatic potential maps (Fig. 7A and 7B) it can be
seen that both studied structure types, I and II, are capable of form-
interaction is shared, as is found for strong covalent or polar bond.
When »
2qb > 0 and is low in magnitude, the electron density is lo-
cally depleted and interaction is closed-shell, as in ionic, hydrogen
or halogen bonds and van der Waals interactions. Hence, the elec-
tron densities and their Laplacians can be used as indicators of the
strengths of hydrogen and halogen bonding interactions. In addi-
tion, the sign of the total electronic energy density (Hb) is a more
ing halogen interactions, because blue ‘‘
r-hole” regions and red
equatorial areas exist. However, the intensities of the colours

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H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
125
Table 7
0.019 to 0.153 a.u.) [59]. Hence, only CAClꢀ ꢀ ꢀO in 3, CAIꢀ ꢀ ꢀO and
CAIꢀ ꢀ ꢀN in 5, CAIꢀ ꢀ ꢀN in 6, CAIꢀ ꢀ ꢀN in 7, and CABrꢀ ꢀ ꢀBr in 8 can
be considered as halogen bonds. Moreover, the dihalogen Brꢀ ꢀ ꢀBr
Topological parameters at H/Xꢀ ꢀ ꢀA BCPs of compounds 3, 5–8.a.
DAH/Xꢀ ꢀ ꢀA
H/Xꢀ ꢀ ꢀA
Compound 3
C4ACl1ꢀ ꢀ ꢀO2
C4ACl1ꢀꢀꢀCl1b
qb
»
2qb
Gb
Vb
Hb
|Vb|/Gb
bonding shows the amphiphilic character of bromine (
equatorial interaction, Fig. 8).
r-hole –
0.0063
0.0039
0.0300
0.0153
0.0060 ꢂ0.0045 0.0015 0.7529
0.0028 ꢂ0.0018 0.0010 0.6363
In all cases, BCPs are characterized by small
qb values, small and
positive
»
2qb values, positive Hb, and with ratio |Vb|/Gb < 1. All
Compound 5
these criteria indicate weak and mainly electrostatic hydrogen
and halogen bonding interactions. Furthermore, we can also eval-
uate their relative strengths since the topological parameters cor-
relate well with the interaction energy. In literature, various
interactions were studied and the linear relationships of the inter-
action energy versus the topological parameters at the BCPs were
obtained [39,59–61]. From those correlations, we have concluded
that interaction energies of hydrogen and halogen bonds in studied
molecules can be classified as weak stabilizing interactions (up to
4 kcal/mol in magnitude) [62]. Among them, NAHꢀ ꢀ ꢀO in 7 is the
strongest.
The same conclusions, i.e. hydrogen and halogen bonding inter-
actions are found from X-ray crystal structure analyses (see Table
3). Hence, we can state that the topological analysis of the DFT
electron density and its results presented here for geometries ta-
ken from the crystal structures may be successfully used to discuss
the nature of hydrogen and halogen bonding interactions.
C11AH11ꢀ ꢀ ꢀN21 0.0125
C21AH21ꢀ ꢀ ꢀO12 0.0104
C15AH15ꢀ ꢀ ꢀO21 0.0077
C25AH25ꢀ ꢀ ꢀO21 0.0084
0.0372
0.0378
0.0245
0.0307
0.0077 ꢂ0.0061 0.0016 0.7899
0.0078 ꢂ0.0061 0.0017 0.7875
0.0053 ꢂ0.0045 0.0008 0.8451
0.0064 ꢂ0.0050 0.0013 0.7925
C16AH16ꢀꢀꢀI21b
C26AH26ꢀꢀꢀI11b
C14AI11ꢀ ꢀ ꢀO11
C24AI21ꢀ ꢀ ꢀN11
0.0054
0.0028
0.0117
0.0171
0.0041
0.0153c 0.0031 ꢂ0.0024 0.0007 0.7699
0.0082c 0.0016 ꢂ0.0011 0.0005 0.7033
0.0383
0.0479
0.0085 ꢂ0.0074 0.0011 0.8738
0.0109 ꢂ0.0098 0.0011 0.9005
b
C14AI11ꢀꢀꢀS21
0.0118c 0.0022 ꢂ0.0015 0.0007 0.6776
Compound 6
N2AH22 Nꢀ ꢀ ꢀS1
C1AH1ꢀ ꢀ ꢀN1
C6AH6ꢀꢀꢀI1b
C3AI1ꢀ ꢀ ꢀN1
0.0100
0.0118
0.0050
0.0126
0.0305
0.0360
0.0063 ꢂ0.0050 0.0013 0.7877
0.0075 ꢂ0.0059 0.0016 0.7911
0.0147c 0.0029 ꢂ0.0022 0.0007 0.7475
0.0355
0.0078 ꢂ0.0067 0.0011 0.8625
Compound 7
N2AH2ꢀ ꢀ ꢀO1
C9AH9Bꢀ ꢀ ꢀO1
C6AH6ꢀꢀꢀI1b
C6AH6ꢀꢀꢀH9Bb
C3AI1ꢀ ꢀ ꢀN1
0.0229
0.0103
0.0052
0.0020
0.0179
0.0963
0.0348
0.0208 ꢂ0.0175 0.0033 0.8414
0.0075 ꢂ0.0064 0.0012 0.8445
0.0148c 0.0030 ꢂ0.0023 0.0007 0.7691
0.0066c 0.0013 ꢂ0.0010 0.0004 0.7315
0.0502
0.0115 ꢂ0.0104 0.0011 0.9069
Compound 8
4. Conclusion
N2AH12 Nꢀ ꢀ ꢀN1 0.0113
N2AH22 Nꢀ ꢀ ꢀN2 0.0140
C1AH1ꢀ ꢀ ꢀBr1 (1) 0.0093
0.0352
0.0403
0.0281
0.0073 ꢂ0.0059 0.0015 0.8007
0.0086 ꢂ0.0072 0.0014 0.8346
0.0057 ꢂ0.0044 0.0013 0.7674
X-ray molecular geometries of investigated 6,7-disubstituted
1,3-benzothiazoles, 3 and 5–8, show no discrepancy from common
molecular geometry of 1,3-benzothiazole and its derivatives. Cal-
culated molecular structures of compounds 3, 5, 6 and 8 are in
agreement with the corresponding X-ray ones, while that of 7 is
different. Gas phase calculations showed that, due to one intramo-
lecular hydrogen CAHꢀ ꢀ ꢀO bond, 7 is planar, while in the crystal
phase two intermolecular NAHꢀ ꢀ ꢀO and CAHꢀ ꢀ ꢀO hydrogen bonds
are formed causing its nonplanarity.
C1AH1ꢀ ꢀ ꢀBr1
0.0046
0.0150c 0.0029 ꢂ0.0021 0.0008 0.7170
(2)b
C4ABr1ꢀꢀꢀS1 (1)b 0.0046c 0.0142c 0.0027 ꢂ0.0019 0.0008 0.6862
C4ABr1ꢀꢀꢀS1 (2)b 0.0013c 0.0040c 0.0007 ꢂ0.0004 0.0003 0.5887
C4ABr1ꢀꢀꢀBr1
0.0069
0.0227
0.0045 ꢂ0.0033 0.0012 0.7315
a
b
c
All unities are given in a.u.
These are not considered as hydrogen or halogen interaction.
Values which are below the limit.
The crystal structures of studied compounds are determined
mostly by weak and dominantly electrostatic hydrogen and halo-
gen bonding interactions. Hydrogen CAHꢀ ꢀ ꢀO/N/Br, NAHꢀ ꢀ ꢀO/N/S
bonds, halogen CAClꢀ ꢀ ꢀO, CAIꢀ ꢀ ꢀO/N bonds and Brꢀ ꢀ ꢀBr interactions
appropriate parameter to gain a deeper understanding of noncova-
lent interactions: when Hb < 0, the interaction is dominantly cova-
lent, but when Hb > 0, the interaction is dominantly electrostatic.
The |Vb|/Gb ratio is even more informative: when |Vb|/Gb > 2, the
interaction is basically covalent, when |Vb|/Gb < 1, the interaction
is basically electrostatic, but when the ratio is in between,
1 < |Vb|/Gb < 2, the interaction is intermediate and need to be con-
sidered as partially covalent and partially electrostatic. The strong
hydrogen and halogen bonds are more covalent in nature, while
the weak ones are mainly electrostatic.
were found. The
p–p interactions participate in additional stabil-
ization of the crystal structures of compounds 3, 5, 6 and 8. The
molecular electrostatic potential maps have indicated possible
hydrogen and halogen bonding interaction sites in structures 3
and 5 (type I), and 6 and 8 (type II). In compounds of the type I
the similar CAClꢀ ꢀ ꢀO (3) and CAIꢀ ꢀ ꢀO and CAIꢀ ꢀ ꢀN (5) halogen
bonding patterns are formed, because chlorine and iodine atoms
are activated by strong electron withdrawing nitro group in ortho
position. Such mono-coordinated halogen bonding interactions
with only one oxygen atom of the nitro group is commonly ob-
served for chlorine, while known tendency of iodine to form bifur-
cated contacts is not observed in studied compounds. In
compounds of the type II, different bonding patterns of halogens
are observed: CAIꢀ ꢀ ꢀN halogen bond in 6, and CAHꢀ ꢀ ꢀBr hydrogen
bond and weak Brꢀ ꢀ ꢀBr dihalogen contact in 8. The most probable
reason for that difference is weaker polar flattening of bromine
than iodine atom. Furthermore, halogens in compounds of the type
II are not additionally activated by good electron withdrawing
group such as nitro group in compounds of the type I.
From the Table 7, it can be seen that obtained qb values for
HBCPs (H stands for hydrogen) are in the range of 0.002–
0.023 a.u., whereas the values of
0.007 to 0.096 a.u. All of these values are not within the common
»
2qb are all positive, ranging from
accepted ranges for H-bonding interactions
(qb ranges from
0.002 to 0.040 a.u.,
39,58]. Some of the
»
»
2qb ranges from 0.020 to 0.150 a.u.) [37–
2qb values are below the bottom limit and
these interactions can not be considered as H-bonds. According
to the results obtained, in crystal structure of 3 there are no H-
bonding interactions, while in the structures 5–8 there are: in 5
four CAHꢀ ꢀ ꢀN/O, in 6 one CAHꢀ ꢀ ꢀN and one NAHꢀ ꢀ ꢀS, in 7 two C/
NAHꢀ ꢀ ꢀO and in 8 one CAHꢀ ꢀ ꢀBr and two NAHꢀ ꢀ ꢀN.
For XBCPs (X stands for halogen),
qb and
»
2qb values are in the
All of the experimentally observed hydrogen and halogen bonds
are confirmed by MEP maps and AIM analysis. Halogen and non-
conventional hydrogen bondings have been shown to be a power-
ful tool in crystal engineering.
range of 0.001–0.018 a.u. and 0.004–0.050 a.u., respectively. Again,
all of these values are not within the ranges for halogen bonding
interactions (qb ranges from 0.006 to 0.049 a.u.,
»
2qb ranges from

ˇ
ˇ
H. Cicak et al. / Journal of Molecular Structure 975 (2010) 115–127
126
Fig. 8. Molecular graph of tetrameric unit of compound 8. Small red dots indicate bond critical points (BCPs). Some values of the Laplacian of the electron density are given
2qb/(a.u.)).
(»
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Crystallographic data for the structure in this paper has been
deposited at Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033; e-mail: de-
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