Secondary interactions in the crystal structures of three 1,2,4,5-tetrakis(bromomethyl)-3,6-bis(2-alkoxy)benzenes

Article abstract of DOI:10.1016/j.molstruc.2012.02.037

Crystal structures of three 1,2,4,5-tetrakis(bromomethyl)-3,6-bis(2-alkoxy) benzenes 1-3 with different length and branching of alkyl chains are analyzed. X-ray structure determinations showed relatively undistorted molecular structures. Crystal packing i

Full text of DOI:10.1016/j.molstruc.2012.02.037

Journal of Molecular Structure 1016 (2012) 109–117
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Secondary interactions in the crystal structures of three
1,2,4,5-tetrakis(bromomethyl)-3,6-bis(2-alkoxy)benzenes
b
c,
Christophe M.L. Vande Velde a, , Matthias Zeller , Vladimir A. Azov
⇑
⇑
a Karel de Grote University College, Department of Applied Engineering, Salesianenlaan 30, 2660 Antwerp, Belgium
b Youngstown State University, One University Plaza, Youngstown, OH 44555-3663, USA
c Department of Chemistry, University of Bremen, Leobener Strasse NW 2C, D-28359 Bremen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 January 2012
Received in revised form 16 February 2012
Accepted 16 February 2012
Available online 28 February 2012
Crystal structures of three 1,2,4,5-tetrakis(bromomethyl)-3,6-bis(2-alkoxy)benzenes 1–3 with different
length and branching of alkyl chains are analyzed. X-ray structure determinations showed relatively
undistorted molecular structures. Crystal packing is defined by networks of C–Hꢀ ꢀ ꢀBr weak hydrogen
bonds, short Brꢀ ꢀ ꢀBr contacts, and one particularly short C–Hꢀ ꢀ ꢀ
p contact, although the major share of
the cohesive energy of the structures is due to dispersion interactions. Z0 = 2 for 1 can be explained in
terms of these interactions, which were shown to be stronger between the asymmetric pairs of molecules
with the help of OPiX calculations. Surprisingly, the role of the oxygen atoms in intermolecular crystal
packing is relatively small.
Keywords:
Crystallography
Non-covalent interactions
Weak hydrogen bonds
Halogen–halogen contacts
Hirshfeld surfaces
OpiX calculations
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
weak hydrogen bonds and C–Brꢀ ꢀ ꢀBr contacts, as well as one C–
Hꢀ ꢀ ꢀ
p contact for the Me-derivative.
The importance of the so called ‘‘weak interactions’’, which in-
clude weak H-bonds, [1] halogen bonds, [2] and various types of
interactions involving
The analysis of intermolecular packing was performed with the
help of Hirshfeld surfaces and fingerprint plots, which represent a
novel approach to the investigation of intermolecular interactions
in crystals [9]. Most commonly, the analysis of such interactions
focuses on an examination of specific interatomic distances and
angles, and short contact distances between atoms in neighboring
molecules are considered to be an indication of important inter-
actions. Use of Hirshfeld surfaces and fingerprint plots opens a
possibility to obtain an unbiased picture of the complete supra-
molecular environment over the whole molecular surface, as well
as to handily define and evaluate the role of particular short
contacts in a crystal structure.
p-systems, [3] in shaping the formation of
crystal lattices of organic compounds is now fully recognized. Dee-
per understanding of such weak interactions is of paramount
importance for the directed creation of new organic materials for
molecular electronics, photovoltaics, nonlinear optics, and other
fields of modern materials science. Thus, investigations into the
nature of weak H-bonds and halogen interactions are the topic of
current interest and active research [4].
Herein we analyze the crystal packing of three 1,2,4,5-tetra-
kis(bromomethyl)-3,6-bis(alkoxy)benzenes 1–3 (Fig. 1) containing
methyl, hexyl, and 2-ethylbutyl side chains. Due to the presence of
four symmetrically disposed bromomethyl groups these kinds of
derivatives were previously employed as intermediates in the syn-
thesis of various molecular architectures, such as polyacenes, [5]
tetrathiafulvalene cages, [6] molecular capsules, [7] and molecular
tweezers. [8] Alkoxy groups were used either for improvement of
solubility, or served as masked hydroxyl groups. Packing motifs
for the three reported compounds show the presence of C–Hꢀ ꢀ ꢀBr
2. Experimental
2.1. Synthesis and crystallization
Compounds 1 [5a] and 2 [6b] were prepared as reported before.
1,2,4,5-Tetrakis(bromomethyl)-3,6-bis(2-ethylbutoxy)benzene
was prepared from 1,4-dihydroxy-2,3,5,6-tetramethylbenzene in
two steps.
1,4-Bis(2-ethylbutoxy)-2,3,5,6-tetramethylbenzene. To a solution
of 1,4-dihydroxy-2,3,5,6-tetramethylbenzene (1.44 g, 8.71 mmol)
in absolute DMF (20 mL), NaH (0.46 g, 19.2 mmol, washed with
⇑
Corresponding authors. Tel.: +32 3 613 19 41 (C.M.L. Vande Velde), tel.: +49 421
218 63126, fax: +49 421 218 63120 (V.A. Azov).
E-mail addresses: Christophe.VandeVelde@KdG.be (C.M.L. Vande Velde), vazov@
uni-bremen.de (V.A. Azov).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2012.02.037

110
C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
The mixture was cooled with an ice bath, the precipitate was fil-
tered off, the organic phase was washed with Na2S2O3 solution
and brine, dried (Na2SO4), and evaporated to dryness. The residue
was recrystallized from hexane/CH2Cl2 to afford a first crop of
the product. The mother liquor was evaporated to dryness, and
the residue was purified by FC (SiO2, PE/CH2Cl2, gradient 0->15%).
Total yield amounted to 1.70 g (2.61 mmol, 79%) of colorless crys-
tals. Rf = 0.35 (CH2Cl2/n-hexane, 1:5). Mp 148–150 °C. 1H NMR
(200 MHz, CDCl3): d = 1.01 (t, 12H, J = 7.4 Hz), 1.50–1.67 (m, 8H),
1.84 (p, 2H, J = 6.0 Hz), 4.05 (d, 4H, J = 6.0 Hz), 4.76 ppm (s, 12H).
13C NMR (50 MHz, CDCl3): d = 11.47, 23.19, 23.47, 42.35, 77.69,
133.47, 153.63 ppm. HR-EI-MS (70 eV): m/z = 645.92745 (M+,
C
22
H
Br4Oþ, calcd. 645.92922).
79
34
2
Fig. 1. Molecular structures of the compounds 1–3.
X-ray quality crystals were grown by slow evaporation of chlo-
roform (1) or dioxane (2) solutions or by slow diffusion of hexane
into a chloroform solution (3).
hexane and dried before addition) was added in small portions at
room temperature within 20 min. Then 1-bromo-2-ethylpropane
(2.68 mL, 19.2 mmol) was added dropwise over a period of 10–
15 min upon cooling with an ice bath. The reaction mixture was
stirred for 3 h at 60 °C and then evaporated to dryness. The residue
was purified by flash chromatography (FC, SiO2, PE/CH2Cl2, gradi-
ent 0–>40%) yielding 1.19 g (3.56 mmol, 41%) of flake-like colorless
crystals. Rf = 0.42 (CH2Cl2/n-hexane, 2:3). Mp 52.5–53 °C. 1H NMR
(200 MHz, CDCl3): d = 0.95 (t, 12H, J = 7.4 Hz), 1.40–1.73 (m,
10H), 2.15 (s, 12H), 3.52 (d, 4H, J = 5.6 Hz). 13C NMR (50 MHz,
CDCl3): d = 11.49, 12.99, 23.44, 42.42, 75.35, 127.85, 151.83. HR-
2.2. X-ray data collection and refinement
Crystals of suitable size were mounted on a Bruker platform
three-circle goniometer with SMART APEX detector, and graph-
ite-monochromated MoK
a tube, and flash-cooled to 100 K. x-
Scans were collected. Data were reduced with the Bruker APEX2
[10] software and scaled and corrected for absorption effects using
SADABS. The structures were solved by direct methods with the
help of SIR92 [11], refinements were carried out by full-matrix
least-square techniques using CRYSTALS [12]. All non-hydrogen
atoms were refined anisotropically. The H atoms were located from
a difference map and initially refined with soft restraints on the
bond lengths and angles to regularize their geometry (C–H in the
range 0.93–0.98 Å) and Uiso(H) (in the range 1.2–1.5 times Ueq of
the parent atom), after which the positions were refined with rid-
ing constraints [13]. Crystal data together with collection and
refinement details for compounds 1–3 are presented in Table 1.
EI-MS (70 eV): m/z = 334.28674 (M+, C22H38Oþ, calcd. 334.28718).
2
1,2,4,5-Tetrakis(bromomethyl)-3,6-bis(2-ethylbutoxy)benzene 3. A
mixture of 1,4-bis(2-ethylbutoxy)-2,3,5,6-tetramethylbenzene
(1.10 g, 3.29 mmol), finely powdered N-bromosuccinimide (NBS,
2.46 g, 13.8 mmol), and dibenzoyl peroxide (40 mg, 0.164 mmol)
was refluxed in 20 mL of carbon tetrachloride for 1.5 h. After
checking the progress of the reaction by NMR an additional
0.5 eq. NBS and a spatula tip of dibenzoyl peroxide were added
to the reaction mixture, which was refluxed for additional 1.5 h.
Table 1
Crystal data, collection and refinement details for compounds 1 and 2.
1
2
3
Formula
Mr
Crystal system, space group
a (Å)
b (Å)
c (Å)
C
12H14Br4O2
C22H34Br4O2
650.12
Monoclinic, P21/c
11.9079 (17)
5.0428 (7)
C22H34Br4O2
650.12
Triclinic, P1
509.86
ꢀ
ꢀ
Triclinic, P1
9.4482(11)
9.7673(14)
10.0131(15)
118.315(2)
107.831(11)
96.19(3)
738.3(2)
2
2.293
10.89
8.610 (3)
8.776 (3)
9.557 (3)
74.914 (4)
64.397 (4)
70.664 (4)
608.6 (4)
1
20.687 (3)
a
(°)
b (°)
102.470 (2)
c
(°)
V (Å3)
1212.9 (3)
2
1.780
6.65
Z
Dcalc (g cmꢁ3
)
1.774
6.63
l
(mmꢁ1
]
F(000)
484
644
322
Crystal color, habit
Crystal size (mm)
Temperature (K)
Colorless, block
0.22 ꢂ 0.39 ꢂ 0.50
100
Colorless, needle
0.55 ꢂ 0.20 ꢂ 0.18
100
Colorless, block
0.36 ꢂ 0.28 ꢂ 0.25
100
Radiation type, wavelength (Å)
Mo K
a, 0.71073
Mo K
a, 0.71073
Mo Ka, 0.71073
H
range(°)
2.4–31.3
1.8–31.3
2.4–31.3
Index range
ꢁ13 ꢃ h ꢃ 12
ꢁ16 ꢃ h ꢃ 16
ꢁ10 ꢃ h ꢃ 12
ꢁ11 ꢃ k ꢃ 12
0 ꢃ l ꢃ 13
ꢁ14 ꢃ k ꢃ 12
0 ꢃ k ꢃ 7
0 ꢃ l ꢃ 14
0 ꢃ l ꢃ 30
Absorption correction
Tmin, Tmax
Multi-scan, SADABS, Bruker APEX2 [10]
0.343, 0.746
0.316, 0.746
0.565, 0.746
No. of reflections measured, independent,
7669, 4364, 3762
6734, 3574, 2883
9836, 3615, 3199
observed [I > 2.0
Rint
No. of reflection, parameters, restraints
R [F2 > 2 (F2)], wR(F2), S
qmin (e Åꢁ3
r(I)]
0.028
0.034
0.022
4364, 164, 0
0.030, 0.073, 1.01
1.42, ꢁ1.06
3574, 127, 0
0.034, 0.092, 0.96
0.97, ꢁ1.08
3615, 127, 0
0.021, 0.055, 1.00
1.19, ꢁ0.50
r
D
D
qmax
,
)

C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
111
ORTEP diagrams were drawn using Ortep-3 for Windows [14].
Crystal structures were analyzed using the PLATON package [15]
as well as with the help of Hirshfeld surfaces and fingerprint plots
[9], prepared using Crystal Explorer 2.1 [16]. Packing diagrams
were prepared with the help of Mercury v. 2.4.6 [17].
identification of the regions of particular interest in relation to
intermolecular interactions.
The combination of di and de in the form of a 2D fingerprint plot
affords a concise summary of intermolecular contacts in the crystal
[19]. Such plots are generated by binning of (di, de) pairs in inter-
vals of 0.01 Å and coloring each bin (a single pixel on the plot) of
the resulting 2D histogram as a function of the fraction of surface
points in that bin. Resolved fingerprint plots can be efficiently used
to identify particular close contacts in the crystal structure, such as
H-bonds or halogen–halogen interactions.
Hirshfeld surfaces became a useful tool for the analysis of inter-
molecular interactions in crystals and were employed in studies of
phenomena such as polymorphism [20], inclusion complexes [21],
pressure-induced effects [20a,22], and others.
2.3. Hirshfeld surface analysis
Molecular Hirshfeld surfaces in crystal structures are based on
the electron distribution calculated as the sum of spherical atom
electron densities of a molecule [18]. The Hirshfeld surface enclos-
ing a molecule is defined by points where the local density in the
crystal equals twice the promolecular density of the single mole-
cule. For each point on such an isosurface two distances are de-
fined: de, the distance from the point to the nearest nucleus
external to the surface, and di, the distance to the nearest nucleus
internal to the surface. The normalized contact distance, dnorm, is a
symmetric function based on both de and di, and the van der Waals
(vdW) radii of atoms internal or external to the surface:
2.4. OPiX calculations
An electron density cube for the crystal geometry of 1 was cal-
culated with Gaussian 03 [23] at the DFT/B3LYP/6-311G⁄ level. The
electron density was used to evaluate packing energies using the
PIXEL method as implemented in the program OPiX [24]. UNI force
field calculations for 1–3 were performed with OpiX. For the OPiX
calculations, the CIFs were modified so that they would contain
v
dw
v
dw
v
dw
vdw
dnorm ¼ ðdi ꢁ ri Þ=ri þ ðde ꢁ re ꢄÞ=re
The value of dnorm is negative/positive when intermolecular
contacts are shorter/longer than vdW separations, enabling
Fig. 2. ORTEP plots of 1–3. Thermal ellipsoids are shown with 50% probability. For compound 1, two asymmetric molecules are labeled as ‘‘A’’ and ‘‘B’’.

112
C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
whole molecules as opposed to symmetry unique half-molecules
(removal of the ꢁx, ꢁy, ꢁz operator and explicit entering of the cor-
responding coordinates), leading to a difference in symmetry oper-
ators between the results of the OpiX calculations and the crystal
structure determinations. For 2, also the origin was shifted by
(ꢁ1/2, ꢁ1/2, ꢁ1/2). The output from these calculations yields a to-
tal packing energy and a breakdown into component interactions.
Each energy is further broken down into its Coulombic (electro-
static), polarization, dispersion and repulsion contributions [25].
reach 1.7(5)° for one of the asymmetric molecules in the crystals
of 1; for the second molecule of 1, as well as for the compounds 2
and 3 torsion angles do not exceed 0.3(5)°. Such relatively small
deviations from planarity are in contrast with hexa(bromo-
methyl)benzene, for which torsion angles reach 6° [26].
In all three compounds, absolute C–C–C–Br torsion angles span
from 76.5(3)° to 91.3(3)°, whereas C–C–O–C angles are in the range
of 83.5(2)–91.7(2)°. The disposition of the six substituents is iden-
tical for 1–3: two CH2Br groups surround an alkoxy substituent, all
of them pointing in the same direction. Thus, two neighboring
CH2Br groups are oppositely oriented, in contrast with 1,2,4,5-tet-
rakis(bromomethyl)benzene, which shows syn orientation for the
two pairs of neighboring CH2Br groups [27]. This arrangement of
the substituents in the dialkoxy derivatives leads to a network
of short intramolecular C–Hꢀ ꢀ ꢀBr and C–Hꢀ ꢀ ꢀO contacts, some of
which may be regarded as weak intramolecular C–Hꢀ ꢀ ꢀBr hydrogen
bonds [28] (Fig. 3). The contacts interconnecting CH2Br and OCH3
groups occur slightly below the sum of van der Waals radii of
the involved atoms [29] (2.94–3.06 Å), with C–Hꢀ ꢀ ꢀBr angles of
142–147°, implying the hydrogen bonding character of the ob-
served interaction according to accepted distance/angle criteria
for crystalline substances [1a,b]. The C–Hꢀ ꢀ ꢀBr contact distances
between the neighboring CH2Br groups are even shorter (2.79–
2.93 Å), but show rather unfavorable donor (129–136°) and accep-
tor (ca. 65°) directionalities. Intramolecular C–Hꢀ ꢀ ꢀO contacts are
shorter still, but unfavorable donor (102–110°) directionalities do
not allow classifying them as weak H-bonds. Taking into account
the inability of the CH2Br groups to find another more favorable
spatial orientation due to congestion of the benzene substituents,
such close contacts may be repulsive in nature.
3. Results and discussion
3.1. Molecular structures
The molecular structures are shown in Fig. 2. Molecules of all
three compounds crystallize on a center of symmetry. Compound
ꢀ
1 crystallizes in space group P1 with Z = 2, and has two symmetri-
cally unrelated half molecules in the asymmetric unit. Both asym-
metric molecules of 1 adopt almost identical conformations, in
which differences in torsion angles for the corresponding substitu-
ents (OCH3 and CH2Br groups) lie within 10°. Bond lengths and an-
gles for the three compounds may be considered normal. The range
of C–Br bond lengths is 1.972(2)–1.982(3) Å, whereas the aromatic
C–C distances lie within the 1.395(4)–1.408(4) Å interval. Despite
the 6-fold substitution, the benzene rings do not show any signif-
icant deviation from planarity. The highest ring torsion angles
3.2. Crystal packing
The main interest of the study focuses on details of supramo-
lecular packing of the compounds. The availability of several
H-bonding sites per molecule together with relatively high
molecular symmetry gave expectations for interesting inter-
molecular packing.
Compound 1 shows the most complex molecular arrangement
with numerous short contacts between the neighboring molecules.
For the analysis of short contacts, Hirshfeld surfaces mapped with
dnorm (Fig. 4) as well as fingerprint plots mapped with different
Fig. 3. Network of short contacts shown on example of one asymmetric molecule of
1. Similar contact patterns are observed in crystals of compounds 2 and 3.
Fig. 4. Plots of dnorm isosurfaces of (a) two asymmetric molecules A and B of 1; (b) molecule of 2; (c) molecule of 3. The position of the short C–Hꢀ ꢀ ꢀ
p contact on the isosurfaces
of molecules 1A (acceptor) and 1B (donor) are indicated with arrows.

C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
113
1A
1B
2
3
(a)
(b)
Br⋅⋅⋅Br
Br⋅⋅⋅H
O⋅⋅⋅H
C⋅⋅⋅H
H⋅⋅⋅H
Fig. 5. (a) Non-resolved fingerprint plots for two asymmetric molecules A and B of 1, as well as for compounds 2 and 3; (b) Fingerprint plots resolved for various modes of
intermolecular interactions. The percentages show the contribution of a particular contact to the total Hirshfeld surface area of molecules. Characteristic features of the
fingerprint plots are marked with arrows.

114
C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
Fig. 6. Two views of intermolecular interactions in the crystal lattice of 1. Dashed lines represent CHꢀ ꢀ ꢀBr (a, c, d; blue, shown only on the left side of the image a), Brꢀ ꢀ ꢀBr (m–
(g, green) contacts. Only the contacts with the distances below the sum of vdW radii of the involved
o; thick black, shown only on the right side of the image a), and C–Hꢀ ꢀ ꢀ
p
atoms are shown. The contact distances are given in Tables 2–3. Rows of the two types of asymmetric molecules are labeled as ‘‘A’’ and ‘‘B’’. (For interpretation of the
references to color in this figure legend, the reader is referred to the web version of this article.)
Table 2
Intermolecular hydrogen bonds for compounds 1–3.a
Compound
D–Hꢀ ꢀ ꢀA
DHꢀ ꢀ ꢀA (Å)
Dꢀ ꢀ ꢀA (Å)
D–Hꢀ ꢀ ꢀA (°)
Symmetry code
1
a
b
c
d
e
f
C12–H123ꢀ ꢀ ꢀO1
C12–H122ꢀ ꢀ ꢀO1
C11–H112ꢀ ꢀ ꢀBr10
C10–H101ꢀ ꢀ ꢀBr4
C4–H41ꢀ ꢀ ꢀBr5
2.61
2.87
3.02
3.02
3.11
3.12
2.60
3.368(4)
3.738(4)
3.775(3)
3.751(3)
3.789(3)
3.756(3)
3.492(4)
137
151
135
133
129
125
152
1 + x, y, z
1 – x, 1 – y, 1 – z
2 – x, 2 – y, 2 – z
x, y, z
1 – x, 2 – y, 1 – z
x, y, –1 + z
C5–H52ꢀ ꢀ ꢀBr11
g
C10–H102ꢀ ꢀ ꢀCgb
x, y, z, 1 – x, 1 – y, 1 – z
2
3
h
i
j
C7–H72ꢀ ꢀ ꢀBr4
C10–H102ꢀ ꢀ ꢀBr5
C8–H82ꢀ ꢀ ꢀBr4
C10–H102ꢀ ꢀ ꢀO1
C5–H52ꢀ ꢀ ꢀBr4
3.12
3.15
3.17
4.101(3)
3.974(3)
3.822(3)
172
143
127
x, –1 + y, z
2 – x, –1/2 + y, 1/2 – z
2 – x, –1/2 + y, 1/2 – z
k
l
2.73
3.13
3.623(2)
3.7666(16)
157
125
–x, –y, 1 – z
1 – x, 1 – y, 1 – z
a
Only the contacts with \(D–Hꢀ ꢀ ꢀA) > 120° are included into the table.
Cg is the centroid of the C1–3,C1i–3i ring of the compound 1.
b
Table 3
Bromine–bromine contacts for compounds 1–3.
Compound
1
C–Brꢀ ꢀ ꢀBr–C
C4–Br4ꢀ ꢀ ꢀBr10–C10
C4–Br4ꢀ ꢀ ꢀBr5–C5
Brꢀ ꢀ ꢀBr (Å)
3.5165(7)
3.6472(8)
C–Brꢀ ꢀ ꢀBr, Brꢀ ꢀ ꢀBr–C (°)
169.51(12), 115.47(10)
78.54(12), 150.37(13)
Symmetry code
m
n
2 – x, 2 – y, 2 – z
1 – x, 2 – y, 1 – z
o
p
q
r
C5–Br5ꢀ ꢀ ꢀBr11–C11
C4–Br4ꢀ ꢀ ꢀBr4–C4
C5–Br5ꢀ ꢀ ꢀBr5–C5
C5–Br5ꢀ ꢀ ꢀBr5–C5
3.6146(8)
3.6638(7)
3.8530(7)
3.5093(12)
78.47(12), 159.07(13)
165.90(7), 100.33(7)
126.11(7) ꢂ 2
x, y, –1 + z
2
3
2 – x, 1/2 + y, 1/2 – z, 2 – x,
–1/2 + y, 1/2 – z
3 – x, 1 – y, 1 – z
143.95(5) ꢂ 2
1 – x, 1 – y, –z

C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
115
modes of intermolecular interactions were drawn and analyzed.
Unresolved fingerprint plots of the two asymmetric molecules
are already remarkably different (Fig. 5a). Analysis of the finger-
print plots resolved for different modes of interactions has shown
that the major difference was due to Oꢀ ꢀ ꢀH and Cꢀ ꢀ ꢀH short con-
tacts (Fig. 5b). Two pointed wedges (marked with arrows, one
associated with the acceptor O-atom of the molecule A, the other
with the donor H-atom of the molecule B) indicate the presence
of strong non-classical CH2ꢀ ꢀ ꢀO hydrogen bonds. The difference be-
tween Cꢀ ꢀ ꢀH-resolved fingerprint plots was especially remarkable,
showing a pair of relatively extended complementary protrusions
on asymmetric molecules (Fig. 5b), marked with arrows). Analysis
of the molecular packing gave evidence of a relatively rare highly
contact is also well-distinguishable on the dnorm fingerprint plots
of the two asymmetric molecules of 1 (Fig. 4a).
Additionally, analysis of fingerprint plots resolved for Brꢀ ꢀ ꢀBr
contacts showed the presence of short and highly directional
Brꢀ ꢀ ꢀBr interactions, appearing as sharp and long traces. Finger-
print plots for Brꢀ ꢀ ꢀH interactions afforded evidence for numerous
C–Hꢀ ꢀ ꢀBr non-classical H-bonds, which show up as two broad
pointed wings. Hꢀ ꢀ ꢀH interactions, although large in surface, show
rather diffuse character.
In the crystal, two symmetrically non-equivalent molecules
pack into infinite chains of molecules A and B (Fig. 6) along the b
axis. The angle between the planes of the benzene rings of the indi-
vidual molecules in chain A relative to chain B amounts to 60.9(2)°.
Whereas the molecules in the chains A are connected by CH2ꢀ ꢀ ꢀBr
interactions c, the chains B are linked by Brꢀ ꢀ ꢀBr contacts n
(Fig. 6a). Between the chains A and B, Brꢀ ꢀ ꢀBr contacts m and n,
as well as CH2ꢀ ꢀ ꢀO hydrogen bonds a and CH2ꢀ ꢀ ꢀBr H-bonds d can
be recognized. All Brꢀ ꢀ ꢀBr contacts belong to the stronger type II
halogenꢀ ꢀ ꢀhalogen interaction according to the classification of
Desiraju et al. [30]. Several additional C–Hꢀ ꢀ ꢀA (A = O or Br) con-
tacts can be recognized slightly above the sum of the vdW radii
of the neighboring atoms involving both bromine and oxygen as
the donor atoms (for the full listing, see Tables 2 and 3). Finally,
symmetric short C–Hꢀ ꢀ ꢀ
located directly above the middle of the benzene ring of molecule
with d(Hꢀ ꢀ ꢀCg(B)) = 2.60 Å and \(C–Hꢀ ꢀ ꢀCg(B)) = 152°. This
p contact: an H-atom of molecule B is
A
the C–Hꢀ ꢀ ꢀ
p contact also links pairs of asymmetric molecules with
each other.
The fingerprint plots of compounds 2 and 3 do not exhibit many
characteristic features (Fig. 5): due to the presence of the extended
alkyl chains, the dnorm contact areas are dominated by diffuse
Hꢀ ꢀ ꢀH and Brꢀ ꢀ ꢀH short contacts. On the Hꢀ ꢀ ꢀH-resolved plot of 3,
one particularly short Hꢀ ꢀ ꢀH contact is denoted by the two sharp
spikes in the low left corner, whereas the Oꢀ ꢀ ꢀH-resolved plot
shows the presence of one Oꢀ ꢀ ꢀH contact. Accordingly, compounds
2 (Fig. 7) and 3 (Fig. 8) only show one particularly close Brꢀ ꢀ ꢀBr
contact each, and 3 has one of the side chain hydrogens contact
the CH2Br hydrogens within the van der Waals distance as well
(Tables 2 and 3). Several CH2ꢀ ꢀ ꢀA (where A = Br, O) ‘‘borderline’’
[31] contacts can be recognized in both structures, although all
contact distances lie slightly above the sum of the vdW radii.
Fig. 7. Intermolecular interactions in the crystal lattice of 2 viewed along the a axis.
Dashed lines represent Brꢀ ꢀ ꢀBr (thick black), and CHꢀ ꢀ ꢀBr (blue) short contacts; the
latter are shown for the d ꢃ (rvdW + 0.2) nm. The contact distances are given in
Tables 2–3. (For interpretation of the references to color in this figure legend, the
reader is referred to the web version of this article.)
Fig. 8. Intermolecular interactions in the crystal lattice of 3 viewed along the a axis. Dashed lines represent Brꢀ ꢀ ꢀBr (thick black), and CHꢀ ꢀ ꢀBr (blue) short contacts; the latter
are shown for the d ꢃ (rvdW + 0.1) nm. The contact distances are given in Tables 2–3. (For interpretation of the references to color in this figure legend, the reader is referred to
the web version of this article.)

116
C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
3.3. OPiX calculations
The third observation is that for compound 1 there is a large
number of intermolecular directional interactions and hydrogen
bonds present in the crystal structure. The majority of them occurs
between the non-symmetry-equivalent molecules and the total
interaction energy between these molecular pairs is much larger
than between the symmetry-equivalent molecular pairs. This leads
to the conclusion that in the case of 1 the structure can trade lower
Z0 against a more optimized packing, which utilizes more of the
functionalities present in the molecules for formation of attractive
intermolecular contacts. This conclusion corresponds well to the
statistical observation that the asymmetric molecular pairs rank
first in the list of intermolecular interaction energies in 55–60%
of the ca. 5000 Z0 > 1 crystals structures investigated in a recent
study [32]. Furthermore, the crystal structure of 1 contains a com-
bination of several different directional supramolecular synthons
The program OPiX was used in order to check whether this
‘‘classic’’ method of studying intermolecular interactions is corrob-
orated by the calculated intermolecular energies, both in a simple
UNI force field calculation for all compounds, and via the PIXEL
method applied to a B3LYP/6-311G⁄ density of compound 1
(Table 4).
Listing all cohesive molecular pairs with interaction energies
over 5 kJ/mol according to the UNI force field (Table 5) leads to four
molecular pairs in compound 2, and six pairs in compound 3. Com-
pound 1 is the most interesting, as there are two symmetry inde-
pendent molecules in the asymmetric unit, and interactions can
be studied between the pairs of symmetric and asymmetric
molecules.
Three clear conclusions can be drawn from these tables: the
first is that the PIXEL energies in general agree relatively well with
the figures from the UNI force field calculations, although the lat-
ter, for 1, has a tendency to overestimate the interaction energy
with respect to the PIXEL method.
The second conclusion is that Brꢀ ꢀ ꢀBr and CHꢀ ꢀ ꢀBr interactions
are by far not the most important factor in the packing of these
crystal structures. The main part of the cohesive energy of the
structures is due to dispersion interactions, with directional inter-
actions playing only a minor role, especially in compounds 2 and 3,
which can be also concluded from examination of their fingerprint
plots (see above).
(CHꢀ ꢀ ꢀBr and CH2ꢀ ꢀ ꢀO hydrogen bonds, Brꢀ ꢀ ꢀBr and CHꢀ ꢀ ꢀ
p interac-
tions) with their particular structural tendencies, which was
shown to be a common feature for structures formed with Z0 > 1
[33].
The cause of such Z0 > 1 packing lies most likely in a discrepancy
between the molecular shape and the character of intermolecular
interactions. In this way, compound 1 obtains better stabilization
not by using the same energetically beneficial directional interac-
tions between two symmetry related molecules, and thus packing
with Z0 = 1, but rather by trading them for different interactions be-
tween symmetrically unrelated molecules, in which the same
hydrogen, bromine and oxygen atoms play different roles as do-
nors or acceptors, providing overall better stabilization.
The better stabilization of the crystal packing of 1 through
numerous intermolecular contacts also corresponds well with its
physical properties: compound 1 has by far the highest melting
point in comparison with 2–3 and 1,2,4,5-tetrakis(bromo-
methyl)benzene and a noticeably lower solubility in common or-
ganic solvents, such as chloroform, benzene, or acetone.
Table 4
Intermolecular interaction energies calculated for 1–3 using PIXEL method and UNI
force field.
D
H PIXEL (B3LYP/6-311G⁄), kJ/mol
DH UNI-FF, kJ/mol
1
2
3
ꢁ225.6
ꢁ255.3
ꢁ195.0
ꢁ170.3
–
–
4. Conclusions
Table 5
As a conclusion we can state that the CH2Br groups play the
most important role in the crystal packing of compound 1. Bro-
momethylene groups participate in the formation of weak hydro-
gen bonds both as H-bond donors and acceptors, and are also
involved in the formation of Brꢀ ꢀ ꢀBr contacts. The role of the O-
atoms in the intermolecular packing is relatively small, since they
barely participate in the formation of H-bonds. Compound 1 dis-
Cohesive molecular pairs with interaction energies over 10 kJ/mol according to PIXEL
method and/or UNI force field. Numbers in bold are the totals for a particular kind of
interaction.
D
kJ/mol
H PIXEL,
D
kJ/mol
H UNI-FF,
Interactionsa
Symmetry coded
1, Aꢀ ꢀ ꢀA
1, Aꢀ ꢀ ꢀB
ꢁ32.7b
ꢁ12.5
ꢁ12.5
ꢁ120.8b
ꢁ38.1
ꢁ18.0
ꢁ8.9
ꢁ35.6b
ꢁ14.9
ꢁ17.5
ꢁ34.3c
ꢁ11.9
ꢁ9.9
ꢁ178.2c
ꢁ50.4
ꢁ20.6
ꢁ11.7
ꢁ28.5c
ꢁ11.4
ꢁ10.1
–
n
x, ꢁ1 + y, ꢁ1 + z
x, ꢁ1 + y, z
plays a complex network of stabilizing CH2ꢀ ꢀ ꢀA, Brꢀ ꢀ ꢀBr, and CHꢀ ꢀ ꢀ
p
short contacts in the crystal. The array of directional interactions
interconnecting the asymmetric pairs of molecules is much more
complex and more stabilizing than the one between the symmet-
rically equivalent ones, which leads to crystallization of 1 with
higher Z0. On the other hand, the presence of the long alkyl substit-
uents in compounds 2 and 3 inhibits close contacts of functional
groups able to participate in directional interactions, preventing
the formation of an extended network of CH2ꢀ ꢀ ꢀA, Brꢀ ꢀ ꢀBr, and
b,d,g
a,o
m
x, y, z
ꢁ1 + x, y, z
ꢁ1 + x, ꢁ1 + y, ꢁ1 + z
1, Bꢀ ꢀ ꢀB
–
c
x, ꢁ1 + y, ꢁ1 + z
x, ꢁ1 + y, z
2
–
–
–
ꢁ89.7
ꢁ18.5
ꢁ14.7
h
p
–
x, ꢁ1 + y, z
CHꢀ ꢀ ꢀ
p contacts, and as a result their packing stabilization is
x, ꢁ1/2 + y, ꢁ1/2 + z
ꢁ1 + x, ꢁ1/2 + y,
ꢁ1/2 + z
mainly based on van der Waals interactions. Finally, examination
of Hirshfeld surfaces and fingerprint plots proved to be a useful
method of analysis for the structures with Z0 > 1 [34], allowing han-
dy determination of asymmetric interactions between the non-
equivalent molecules.
3
–
–
–
–
ꢁ58.8
ꢁ34.0
ꢁ26.3
ꢁ17.3
k
–
–
l
ꢁ1 + x, y, z
ꢁ1 + x, y, 1 + z
ꢁ1 + x, 1 + y, z
x, ꢁ1 + y, z
a
b
c
See Tables 2 and 3 for designation of the numbers.
Polarization is not included in the interaction energies for molecular pairs.
Molecular pairs with energy contributions below the cut-off implemented in
Supplementary material
CCDC 860468–860470 contain the supplementary crystallo-
graphic data for 1–3. These crystallographic data can be obtained
free of charge from via http://www.ccdc.cam.ac.uk/conts/retriev-
OPiX could not be included into these sums.
Symmetry codes used for OPiX calculations differ from the ones used for crystal
descriptions, see Section 2.
d

C.M.L. Vande Velde et al. / Journal of Molecular Structure 1016 (2012) 109–117
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