Examination of halogen bonding interactions in electronically distinct but structurally related Tris(haloarenes)

Article abstract of DOI:10.1021/cg9008625

Solid-state halogen bonding interactions present in four families of structurally similar tritopic haloarenes were examined in an effort to identify molecular features that promote halogen-...-carbonyl, halogen- ... halogen, and/or halogen ... π interacti

Full text of DOI:10.1021/cg9008625

DOI: 10.1021/cg9008625
Examination of Halogen Bonding Interactions in Electronically Distinct
but Structurally Related Tris(haloarenes)
2010, Vol. 10
224–231
F. Christopher Pigge,*,† Venu R. Vangala,†,§ Dale C. Swenson,† and Nigam P. Rath‡
‡
†Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, and Department of Chemistry &
Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri 63121.
§ Current address: Institute of Chemical and Engineering Sciences, A*STAR, Singapore.
Received July 23, 2009
ABSTRACT: Solid-state halogen bonding interactions present in four families of structurally similar tritopic haloarenes were
examined in an effort to identify molecular features that promote halogen carbonyl, halogen halogen, and/or
3 3 3
3 3 3
halogen π interactions. The substrates used in this study all featured three haloarene substituents attached to a central
3 3 3
1,3,5-substituted arene ring with conformationally flexible linkers (ketone or ester groups) in order to systematically vary the
polarization of the aryl halogen groups. Within each individual substrate type, however, there was found to be little correlation
in the halogen bonding motifs exhibited as a function of halogen present (I, Br, and Cl). In general, the iodoarene derivatives
examined exhibited a greater degree of halogen bonding interactions than the bromo and chloro analogues, and a unique
bifurcated I I/I OdC halogen bonding synthon was identified in two substrates. Halogen bonding contacts observed in
3 3 3 3 3 3
tritopic iodoarenes correlated nicely with electrostatic potentials of simpler model compounds determined using computational
methods. This study highlights the difficulty in attempting to empirically correlate halogen bonding with molecular structure.
Introduction
ing a greater fundamental understanding of solid-state halo-
gen bonding (along with its inherent limitations) will benefit
efforts in crystal engineering by ultimately allowing research-
ers to predictably invoke such interactions in combination
with other noncovalent attractions in the rational design of
functional materials.11
Halogen bonding is a type of noncovalent interaction
that occurs between organic, inorganic/organometallic, or
diatomic halogens and Lewis basic electron pair donors.1
Halogen bonds are primarily electrostatic attractions that
are made possible by anisotropy in the electron density
surrounding most halo substituents, particularly I, Br, and
Cl. In organic halogens, this unequal distribution of electron
density produces regions of positive electrostatic potential
along the axes of C-X bonds. Approach of electron donors
(N, O, or another halogen) along this vector can then result in
energeticallyfavorable interactions.2 Halogen bondsare gene-
rally regarded as weak interactions (weaker than hydrogen
bonds) but are highly directional. However, the strength of
halogen bonding interactions can be modulated by neighbor-
ing groups, particularly functionality that serves to increase
the electrophilic character of the halogen, which often leads to
a corresponding increase in halogen bonding ability.3
Structurally defining halogen bonding interactions are
typically manifested in the solid state, and crystal engineering
studies over the past decade have demonstrated the ability of
halogen bonding to influence or control the supramolecular
structures of extended molecular assemblies.1 Recent applica-
tions of solid-state halogen bonding in mediating assembly of
organic conductors and magnets,4 chemical separation
agents,5 NLO-active materials,6 liquid crystals,7 and porous
organic solids8 have been reported. Additionally, evidence for
solution phase halogen bonding operative in novel molecular
receptors9 and in biological host-guest systems10 has been
obtained. Despite these impressive achievements, there is still
much to uncover regarding the nature of halogen bonding and
the reliability of such interactions, particularly in the face of
potentially competing noncovalent attractions. In turn, gain-
An approach toward achieving a better understanding of
halogen bonding hierarchies and the relative importance of
various halogen bond types entails structurally characterizing
closely related polyfunctional compounds that differ in the
identity of their halogen substituents. In tandem with subtle
variations in the electronic characteristics across a family of
organohalogens, it may be possible to ascertain the signifi-
cance of specific halogen bonding synthons as a function of
molecular structure. Toward this end, we have prepared a
series of tritopic haloarene derivatives designed to probe the
interplay of CdO X and X X halogen bonding with
3 3 3
3 3 3
electronic effects arising from the substitution pattern of the
arene. Importantly, we have chosen to investigate conforma-
tionally flexible haloarenes in order to accommodate the
significant size differences between the halogens. Our thinking
is that a family of analogous organohalides will be better
equipped to maintain energetically significant halogen bond-
ing interactions if the molecular conformation can be adjusted
according to the identity of the halide. This feature should
attenuate the influence that large iodine substituents can
sometimes exert over solid-state structures, especially in con-
formationally rigid molecules.12
We have previously reported the solid-state halogen bond-
ing patterns found in 4-halotriaroylbenzenes 1a-1d
(Scheme 1).13 In this family, the bromo and chloro derivatives
1b and 1c were found to be isostructural, and two distinct
types of CdO X halogen bonds were prominently featured
3 3 3
in the crystalline networks. Solid solutions prepared from 1b/
1c were also characterized. In contrast, the iodo analogue 1a
exhibited a different halogen bonding pattern in which one
iodoarene participates as both electrophile and nucleophile in
*To whom correspondence should be addressed. E-mail: chris-pigge@
uiowa.edu.
r
pubs.acs.org/crystal
Published on Web 09/10/2009
2009 American Chemical Society

Article
Crystal Growth & Design, Vol. 10, No. 1, 2010 225
a bifurcated halogen bond with CdO and ArI partners, and a
second iodoarene functions solely as an electrophile in an
Scheme 1. Conformationally Flexible Haloarenes Examined in
This Studya
I
I contact. The third iodoarene does not appear to be
3 3 3
involved in any intermolecular associations. Not surprisingly,
the fluoro analogue 1d did not exhibit any halogen bonding
contacts. Our conclusions from this study are that Cl/
Br OdC interactions are preferred over Cl Cl and
Br Br in this system, but incorporation of an iodine group
results in formation of I I contacts at the expense of
3 3 3
3 3 3
3 3 3
3 3 3
additional I OdC bonds. In subsequent work, we prepared
3 3 3
and characterized the tritopic iodophenoxy ester 2a that
possesses more electron-rich iodoarene substituents relative
to those found in 1a.14 Triester 2a formed an inclusion host
framework mediated by a combination of symmetry, solvent
templation, and bifurcated I OdC and I π halogen
bonding. Guest solvent molecules (CHCl3, benzene, or
pyridine) were included in nanometer-sized channels. A close
packed form of 2a was also characterized and found to exhibit
3 3 3
3 3 3
I
OdC and I π halogen bondinginteractionsas well. We
3 3 3
3 3 3
attribute (at least in part) the appearance of I π interactions
3 3 3
in 2a to the nucleophilicity of the iodophenoxy rings arising
from the electron-donating oxygen atoms. Notably, such
interactions were not observed in 1a. To further examine the
halogen bonding patterns found in conformationally flexible
carbonyl-containing haloarenes related to the compounds
discussed above, we have prepared and structurally character-
ized tritopic bromo, chloro, and fluoro phenoxy esters 2b-2d,
isomeric iodo- and bromo-esters 3a-3b, and 3-halotriaroyl-
benzenes 4a-4b. The results of this effort along with
a comparative analysis of the relationship between mole-
cular structure and halogen bonding interactions are reported
herein.
a Structures reported in this paper are indicated with an asterisk (*).
Phloroglucinol Ester 3b. This material was prepared using the
procedure given above except that 4-bromobenzoyl chloride was
used in place of 4-iodobenzoyl chloride. Yield: 52%, mp 162-
164 °C. 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J=8.6 Hz, 6H), 7.67
(d, J = 8.6 Hz, 6H), 7.17 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
163.9, 151.9, 132.3, 129.5, 128.3, 113.5, 107.7. Anal. Calcd. for
Experimental Section
C
27H15Br3O6: C 48.04, H 2.24. Found: C 47.65, H 2.36.
3-Halotriaroylbenzenes 4a and 4b. These triaroylbenzenes were
Halophenoxy Esters 2b-2d. These substrates were prepared from
trimesic acid chloride and the appropriate 4-halophenol using
previously reported procedures.14 Compound characterization data
are given below.
prepared from 3-iodoacetophenone and 3-bromoacetophenone,
respectively, according to previously published procedures.13,15
1
4a: Mp 138-140 °C. H NMR (300 MHz, CDCl3) δ 8.32 (s, 3H),
1
8.14 (t, J=1.7 Hz, 3H), 7.91 (m, 3H), 7.71 (m, 3H), 7.25 (t, J=7.8
Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 193.1, 142.3, 138.8, 138.3,
138.0, 134.4, 130.5, 129.3, 94.8. Anal. calcd. for C27H15I3O3: C
Trimesic Acid Ester 2b. Mp 188-189 °C. H NMR (300 MHz,
CDCl3) δ 9.21 (s, 3H), 7.59 (d, J=8.8 Hz, 6H), 7.18 (d, J=8.8 Hz,
6H). 13C NMR (75 MHz, CDCl3) δ 163.1, 149.7, 136.4, 133.0, 131.2,
123.5, 119.8. Anal. calcd. for C27H15Br3O6: C 48.04, H 2.24. Found:
C 48.02, H 2.32.
1
42.22, H 1.97. Found: C 42.12, H 1.89. 4b: Mp 140-142 °C. H
NMR (300 MHz, CDCl3) δ 8.38 (s, 3H), 8.03 (t, J = 1.6 Hz, 3H),
7.70 (m, 6H), 7.44 (t, J=9.4 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
193.2, 138.3, 138.1, 136.4, 134.4, 132.9, 130.5, 128.7, 123.3. Anal.
Calcd. for C27H15Br3O3: C 51.71, H 2.41. Found: C 51.55, H 2.31.
X-ray Crystallography. Single crystals of 2-4 were grown by slow
evaporation of CH2Cl2 or CH2Cl2/MeOH solutions. Diffraction
data were collected using either a Nonius-Kappa CCD or a Bruker
APEXII CCD diffractometer. Crystallographic data are shown in
Table 1. Details concerning structure solution and refinement can
be found in the Supporting Information (CIF).
1
Trimesic Acid Ester 2c. Mp 194-195 °C. H NMR (300 MHz,
CDCl3) δ 9.22 (s, 3H), 7.45 (d, J=8.9 Hz, 6H), 7.24 (d, J=8.9 Hz,
6H). 13C NMR (75 MHz, CDCl3) δ 163.2, 149.2, 136.4, 132.1, 131.2,
130.0, 123.1. Anal. calcd. for C27H15Cl3O6: C 59.86, H 2.79. Found:
C 59.72, H 2.74.
1
Trimesic Acid Ester 2d. Mp 157-158 °C. H NMR (300 MHz,
CDCl3) δ 9.31 (s, 3H), 7.41-7.02 (m, 12H). 13C NMR (75 MHz,
CDCl3) 163.5, 162.4, 159.2, 146.5, 136.4, 131.3, 123.2, 123.1, 116.8,
116.5. Anal. calcd. for C27H15F3O6: C 65.86, H 3.07. Found: C
65.68, H 3.16.
Computations. Electrostatic potential surfaces were generated for
model iodoarenes 5-8 from DFT calculations performed at the
B3LYP/6-31G (d,p) level.16 Potential surfaces were mapped by
Phloroglucinol Ester 3a. Phloroglucinol (0.81 g, 5.0 mmol), 4-
iodobenzoyl chloride (4.13 g, 15.5 mmol), Et3N (2.2 mL, 15.5
mmol), and DMAP (0.20 g) were combined in 20 mL of CH2Cl2.
The reaction was stirred at room temperature for 4 h. Water was
then added and the layers were separated. The aqueous phase was
extracted with additional CH2Cl2 and the combined organic layer
was washed with 10% aq. HCl solution, 5% aq. NaOH solution,
and brine, followed by drying over anhydrous MgSO4. Filtration
and removal of the solvent afforded a crude product that was
purified by flash column chromatography (SiO2, hexanes/EtOAc)
to afford 3a as a colorless solid (2.32 g, 57%). Mp 192-193 °C. 1H
NMR (300 MHz, CDCl3) δ 7.86 (br. s, 12H), 7.16 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ 164.2, 151.6, 138.3, 131.8, 128.6, 113.5, 102.3.
Anal. Calcd. for C27H15I3O6: C 39.71, H 1.84. Found: C 39.45, H
1.81.
3
˚
conventional molecular electron density (0.002 electron/A ) and
color-coding. Crystal structure coordinates for 1a, 2a, 3a, and 4a
provided the basis for the simpler model compounds 5-8, respec-
tively. The structures were truncated to simplify the calculations and
the torsion angles of the resulting benzophenones and aryl benzoate
esters were fixed to mimic the molecular conformation found in the
solid state. Bond lengths and angles were not constrained so as to
attain the nearest local minima.
Results and Discussion
Our previous study of solid-state halogen bonding patterns
in 4-halotriaroylbenzenes 1 revealed significant differences

226 Crystal Growth & Design, Vol. 10, No. 1, 2010
Pigge et al.
Table 1. Crystallographic Data
2b (CH2Cl2)0.43
3
2c (CH2Cl2)0.34
3
3
3
(CH3OH)0.26
(CH3OH)0.09
2d
3a CH2Cl2
3
3b
4a
4b
cryst syst
space group
monoclinic
C2/c
46.434(5)
3.9139(5)
34.656(4)
90
120.273(5)
90
5439.4(11)
8
1.758
monoclinic
P21/n
3.8968(5)
21.877(3)
29.152(3)
90
91.083(5)
90
2484.8(5)
4
1.532
monoclinic
P21/c
19.872(2)
3.8652(5)
28.764(3)
90
90.584(5)
90
2209.2(4)
4
1.480
monoclinic
P21/n
4.2535(3)
41.981(3)
15.1423(12)
90
97.928(4)
90
2678.1(3)
2
2.129
monoclinic
P21/c
3.8321(5)
27.975(3)
23.031(3)
90
90.108(6)
90
2469.0(5)
4
1.816
monoclinic
P21/c
11.9616(13)
14.2501(15)
14.9466(16)
90
106.816(5)
90
2438.8(5)
4
2.092
monoclinic
P21/c
11.6382(13)
14.1355(15)
14.9051(16)
90
109.070(5)
90
2317.5(4)
4
1.797
˚
a/A
˚
b/A
˚
c/A
R/°
β/°
γ/°
3
˚
V/A
Z
Dcalc
μ (mm-1)
T/K
4.576
0.485
0.121
3.643
4.944
3.872
5.250
210(2)
53881
6183
4717
389
190(2)
15103
4191
2777
367
210(2)
41938
4997
4080
325
100(2)
49424
5182
4598
331
100(2)
34122
4308
3281
326
150(2)
55068
5589
4907
303
190(2)
40352
5308
4200
298
no. of reflns
no. of unique reflns
no. of reflns with I > 2σ(I)
no. of params
R1 [I > 2σ(I)]
wR2 (all reflns)
0.0378
0.0886
0.0551
0.1189
0.0353
0.0918
0.0736
0.1698
0.1618
0.3691
0.0225
0.0498
0.0325
0.0739
between the iodo-substituted compound as compared to the
bromo/chloro analogues.13 Given this observation we were
interested in examining the effect of perturbing the electronics
of the haloarene substituents while nominally preserving the
gross molecular structures. Consequently, the trimesic acid
esters 2 and the phloroglucinol benzoates 3 were prepared and
characterized. In 2, the haloarene rings are now more electron
rich due to the presence of electron donating ester oxygen
atoms. This feature should attenuate the electrophilicity of the
para-halogen atoms while also rendering the ester carbonyl
groups less Lewis basic than the ketone functional groups
found in 1. Conversely, in 3 electron withdrawing groups
remain positioned para with respect to the halogens but in
the form of an ester linkage rather than a ketone carbonyl.
Several solid-state inclusion compounds and a nonsolvated
close-packed structure of iodo-substituted trimesic acid ester
2a were reported previously.14 Both types of structures ex-
hibited a combination of I OdC and I π interactions.
3 3 3
3 3 3
Hexagonal nanoporous inclusion complexes with pyridine,
CHCl3, and benzene solvates were further mediated by sym-
metry and solvent templation. The preparation of similar
inclusion complexes from the bromo congener 2b was at-
tempted, but crystallization from the solvents listed above
failed to produce single crystals. Slow evaporation of a
CH2Cl2/MeOH solution of 2b, however, afforded X-ray
quality crystals and a view of the structure illustrating the
principal intermolecular interactions is shown in Figure 1.
Individual molecules of 2b adopt an approximately C3 sym-
metrical orientation and form discrete supramolecular dimers
mediated by a pair of type II Br Br halogen bonds.17
3 3 3
Disordered CH2Cl2 solvate molecules are housed within the
macrocycles formed as a consequence of this dimerization,
while methanol solvates (also disordered) reside in channels
between supramolecular macrocycles. There appear to be no
significant Br OdC or Br π interactions, unlike the
Figure 1. View of Br Br interactions in 2b. Halogen bonding
3 3 3
˚
metrics: dBr
= 3.78 A, C-Br Br angles = 142.6°, 83.7°.
3 3 3
Br
3 3 3
3 3 3
3 3 3
Halogen bonding is indicated by dashed lines; CH2Cl2 and MeOH
solvates are omitted for clarity.
situation encountered in structures of 2a. Dimeric arrays of
2b stack in superimposed sheets along the b axis.
The crystal structure of chloro analogue 2c (also obtained
as a channel-type inclusion complex with disordered CH2Cl2
and MeOH solvates) differs markedly from both 2a and 2b. In
motif and there are no significant Cl Cl close contacts.
3 3 3
Thus, the crystal structures of 2a (nonsolvated), 2b, and 2c
each exhibit distinct and nonidentical halogen bonding inter-
actions that vary as a function of halogen identity.
Not surprisingly, the 4-fluorophenoxy trimesic acid ester
does not exhibit any contacts that can be categorized as
halogen bonding interactions, and this reflects the general
this structure, molecules of 2c are connected via Cl OdC
3 3 3
halogen bonds to form undulating ribbon-like chains
(Figure 2). Additional solid-state C-H O hydrogen bonds
(not shown in Figure 2) appear to further reinforce this ribbon
3 3 3

Article
Crystal Growth & Design, Vol. 10, No. 1, 2010 227
Figure 3. Helical chains exhibiting C-H F hydrogen bonding in
3 3 3
the structure of 2d. C-H F hydrogen bonds indicated by dashed
3 3 3
˚
lines: dH F = 2.75 A, C-H F = 153.7°, C-F H = 152.5°.
3 3 3 3 3 3
3 3 3
Figure 2. Ribbon motif maintained by CdO Cl halogen bonds
in 2c. Relevant distances and angles: dCl
3 3 3
3 3 3
˚
= 3.23 A,
OdC
C-Cl O = 154.3°, CdO Cl = 111.5°. Solvate molecules
omitted for clarity.
3 3 3 3 3 3
correlation between halogen bonding ability and halogen
polarizability.1,2 The structure of 2d does display several types
of weak hydrogen bonding contacts, however, including
examples of C-H F hydrogen bonds.18 These hydrogen
3 3 3
bonds serve to connect individual molecules to give rise to
helical chains as shown in Figure 3. Given the lack of halogen
bonding evident in the structure of 2d and the absence of
meaningful halogen bonding interactions in the 4-fluoro-
(triaroylbenzene) 1d,13 characterization of the fluoro deriva-
tives of 3 and 4 was not pursued.
The trimesic acid esters described above feature halo-
phenoxy rings arrayed about a central arene core. The 4-
halobenzoate esters prepared from phloroglucinol (3a and 3b)
represent topologically similar tritopic haloarenes in which
the electronic effects of the ester linkage are reversed relative
to 2. Consequently, we anticipated a priori that the para
electron withdrawing carbonyl group would increase the
electrophilicity of the halogen substituents, resulting in a
corresponding increase in the likelihood of halogen bond
formation relative to what we observed in 2a-2c.
Figure 4. View of halogen bonding interactions in 3a. CH2Cl2
solvates omitted for clarity. Relevant distances and angles: dI 3 3 3
=
I
˚
˚
3.89 A, dI 3 3 3 = 3.07 A, C-I I angles = 163.8° and 94.7°,
O
3 3 3
C-I O = 163.7°, CdO I = 143.2°.
3 3 3 3 3 3
halogen bond donor (electrophile) toward the Lewis basic
carbonyl group and a halogen bond acceptor (nucleophile)
toward neighboring electrophilic iodoarenes. The third io-
doarene moiety does not appear to be involved in any non-
covalent interactions. Notably, the halogen bonding motif
operative in the structure of 3a closely resembles the halogen
bonding pattern identified in 4-iodotriaroylbenzene 1a.13
Crystals of 3a were obtained as an inclusion complex with
CH2Cl2. The solvates reside in channels oriented down the a
axis and are disordered about an inversion center. A view of
the extended packing is shown in Figure 5.
Crystals of 3a CH2Cl2 were obtained from slow evapora-
3
tion of a CH2Cl2 solution. Individual molecules were found to
stackinlayersconnectedbya helicalchain of halogen bonding
interactions. A partial view of the structure is shown in
Figure 4 that illustrates the major intermolecular solid-state
attractions. Two of the three iodo-arene units in molecules of
3a are engaged in halogen bonding. One iodo group forms
bifurcated contacts with another iodine substituent and a
carbonyl oxygen atom. Thus, this iodine functions as a
Crystals of the tris(bromobenzoate) ester of phloroglucinol
(3b) were also obtained from a CH2Cl2 solution; however,
these crystals proved to be quite fragile and diffracted poorly.

228 Crystal Growth & Design, Vol. 10, No. 1, 2010
Pigge et al.
Figure 5. View of extended packing (down a) in 3a CH2Cl2. Sol-
3
vate molecules shown in blue.
Figure 7. Four-point C-H O hydrogen bonding interaction
observed in 4a and 4b (structure of 4a illustrated). See text for H-
bonding metrics.
3 3 3
single crystals of this last derivative have not been successfully
obtained. X-ray quality crystals of both iodo (4a) and bromo
(4b) analogues, however, were grown from CH2Cl2 solution
and diffractometry revealed these two crystals to be isostruc-
tural. Iodo derivative 4a, however, exhibits minor rotational
disorder (∼2%) about one of the aryl - CdO bonds. Rather
than halogen bonds, the dominant intermolecular interaction
present in these structures appears to be centrosymmetric
four-point recognition patterns involving two unique
Figure 6. Extended packing in 3b viewed down a.
Consequently, diffraction data could only be refined to an R
value of ∼16% and so discussions concerning specific non-
covalent attractions must be approached with caution. The
poor quality of the diffraction data notwithstanding, exam-
ination of the extended network present in 3b reveals no
significant halogen bonding interactions. Indeed, 3b crystal-
lizes as a close-packed structure seemingly mediated by var-
C-H O hydrogen bonds (Figure 7). The “outer” H-bond-
3 3 3
ing interactions are longer and more distorted from ideal
˚
geometry (dH O = 2.69 A, C-H O = 132.4°) compared
3 3 3
3 3 3
to the two equivalent “inner” hydrogen bonds (dH 3 3 3
=
O
˚
2.46 A, C-H O = 160.3°), but both contacts fall within
the range of attractive interactions. Similar distances and
angles were found in the structure of bromo derivative 4b
3 3 3
ious C-H O and perhaps C-H Br hydrogen bonds.
3 3 3 3 3 3
The structure is composed of two-dimensional sheets that
stack directly on top of each other down the a axis as shown in
Figure 6. Within each layer individual molecules are aligned in
vertical rows in a “head-to-tail” fashion, withadjacent vertical
rows running in antiparallel directions. The extended packing
in the ac plane shows the presence of distinct and noninterpe-
netrated layers. Thus, the network assemblies found in 3a and
3b differ significantly, not just in their overall topology but
also (somewhat surprisingly) by the presence of multiple
halogen bonding interactions in 3a and the complete absence
of such interactions in 3b. The tris(4-chlorobenzoate) phloro-
glucinol ester was prepared as well, but unfortunately efforts
to secure X-ray quality crystals of this material have failed.
A final molecular scaffold examined in this study is based
on the 1,3,5-triaroylbenzene framework and so is directly
structurally related to 1. In 4a and 4b, however, the halogen
substituents have been moved to meta positions relative to the
ketone carbonyls, and this positioning is expected to diminish
the halogen bonding activating effect of these electron with-
drawing groups. The iodo, bromo, and chloro analogues of 4
have all been prepared using established procedures, but
˚
(d=2.60, 2.42 A, 133.8, 167.7°). Notably, a similar four-point
hydrogen bonding motif (exhibiting comparable H-bond dis-
tances and angles) was encountered in a nonsolvated structure
of a triaroylbenzene derivative that possessed NO2 groups in
place of the halogen substituents.19
Halogen bonding interactions are nominally present in the
structures of 4a and 4b, although in these instances arene π
systems function as the halogen bond acceptors. These X
π
3 3 3
interactions (X = I, Br) serve to connect the discrete dimeric
supramolecular assemblies of the type illustrated in Figure 7
to adjacent H-bonded dimers resulting in generation of
supramolecular columns aligned down the a axis.20 The
association of two such dimers via I π interactions is
3 3 3
illustrated in Figure 8 in which halogen bonds have been
drawn to the centroids of the arene acceptors. Two distinct
types of I π contacts are observed to converge upon a single
3 3 3
arene ring, and both exhibit relatively short I πcentroid
3 3 3
˚
distances (3.57 and 3.61 A) and near linear C-I πcentroid
angles (150.6 and 157.0°). The bromo analogue 4b displays
comparable halogen bonding angles about the relevant aryl
3 3 3

Article
Crystal Growth & Design, Vol. 10, No. 1, 2010 229
Table 2. Summary of Solid-State Halogen Bonding Interactions
Observed in 1-4
interaction
1
2
3
4
I
I
I
I
OdC
π
þþþ
þþþ
---
---
þþþ
þþþ
---
---
---
---
---
3 3 3
3 3 3
3 3 3
þþþ
þþþ
þþþ
---
---
---
þþþ
Br Br
---
þþþ
---
---
3 3 3
Br OdC
Br π
Cl Cl
Cl OdC
Cl
3 3 3
---
---
---
þþþ
3 3 3
nca
nc
nc
nc
3 3 3
þþþ
þþþ
3 3 3
3 3 3
π
---
---
nc
nc
a No crystals were obtained.
Scheme 2. Halogen Bonding Synthons Exhibited in 1-4 along
with Idealized Geometriesa
Figure 8. Linking of hydrogen bonded dimers in 4a via putative
I
π interactions (shown in blue).
3 3 3
a Bifurcated interaction IV was observed exclusively in iodoarene
derivatives 1a and 3a.
halogen atoms as well as carbonyl groups. Given the presence
of multiple and seemingly mutually reinforcing four-point
hydrogen bonding interactions in this system, the X
π
3 3 3
interactions observed may represent secondary contacts that
support the supramolecular network but do not exert direct-
ing effects upon its formation. While the contacts in question
certainly meet the distance and angle criteria established for
X
π halogen bonding, electronic factors in the molecular
3 3 3
building blocks should attenuate the energetic significance of
these putative interactions.
The substrates examined in this study were designed to
probe the interplay between specific types of halogen bonding
interactions (X X, X OdC, and X π) in structurally
3 3 3
3 3 3
3 3 3
similar but electronically distinct systems (Scheme 2). At the
outset we were hopeful that clear trends in halogen bonding
behavior would emerge, but this has largely proved not to be
the case. A summary of halogen bonding interactions ob-
served across all four substrate families is provided in Table 2.
The most meaningful comparisons can be drawn between the
iodo- and bromo-substituted derivatives as crystal structures
of 1a-4a and 1b-4b were successfully obtained. The only
instance in which similar halogen bonding interactions are
evident is found in 4a and 4b as crystals of these two
compounds are isostructural. The significance of the putative
halogen bonding contacts in 4a and 4b (I π and Br π,
Figure 9. View of 4a down b. Hydrogen bonding shown as dashed
lines, I π interactions from Figure 8 shown as solid black lines,
3 3 3
I
π interactions connecting adjacent rows shown in green.
3 3 3
bromines (150.4 and 161.5°) with somewhat shorter
˚
πcentroid distances (3.47 and 3.49 A).
Br
3 3 3
A view of the extended packing observed in 4a (as well as
4b) is shown in Figure 9 to illustrate the arrangement of
hydrogen/halogen bonded ribbons in parallel rows. Interest-
ingly, close contacts betweenan arene π system in one rowand
a halogen in an adjacent row are present; however, the arene
involved possesses a 1,3,5-tricarbonyl substitution pattern
and so is extremely deactivated toward participation in halo-
gen bonding. This contact, then, may arise simply as a
consequence of other crystal packing forces. Indeed, all the
halogen-π interactions found in 4a,b involve deactivated
arenes substituted with inductively electron withdrawing
3 3 3
3 3 3
respectively), however, is tempered by the presence of see-
mingly more significant C-H O hydrogen bonds and the
3 3 3
3 3 3
recognition that the close X π contacts may well be a
consequence of lattice-imposed proximity. In contrast, the
halogen bonding interactions in 1-3 do appear to be energe-
tically significant, but the patterns present in I/Br substrate
pairs 1a/1b, 2a/2b, and 3a/3b have little in common. It is

230 Crystal Growth & Design, Vol. 10, No. 1, 2010
Table 3. Electrostatic Potential Maps of Model Iodoarenes 5-8a
Pigge et al.
a Blue represents areas of positive electrostatic potential and red represents areas of negative electrostatic potential. Relative electrostatic potential
values were determined on a scale of -25 to þ25 kcal mol-1
.
interesting to note, however, that the bifurcated I I and
3 3 3
positions (5 and 7) exhibit the greatest polarization and so
would be expected to be better halogen bond donors than the
iodo groups in 6 and 8. This feature is borne out experimen-
tally in that triaroylbenzene 1a and phloroglucinol ester 3a
seemingly exhibit more halogen bonding contacts than 2a and
I
OdC synthon observed in 4-iodo(triaroylbenzene)13 de-
3 3 3
rivative 1a is also present in phloroglucinol iodobenzoate 3a
and that both of these substrates feature an iodoarene acti-
vated for enhanced halogen bonding by the presence of an
electron withdrawing group at the para position. While
4a. Moreover, the bifurcated I I/I OdC interactions in
3 3 3 3 3 3
analogous I OdC interactions have been observed in inter
both 1a and 3a appear to constitute the principal mode of
noncovalent bonding in the respective crystals. In contrast,
the halogen bonding interactions in solvated forms of 2a
(I π and I OdC) occur in combination with solvent
3 3 3
alia structurally simpler p-iodophenyl aldehydes, ketones and
esters,21 incorporation of an additional iodo group to form a
three-centered halogen bonding chain does not appear to be
common. The presence of multiple iodoarene units within
individual molecular building blocks and conformational
3 3 3
3 3 3
templating and symmetry effects to produce metastable hexa-
gonal nanoporous structures,14 while those in 4a (I π)
3 3 3
flexibility may facilitate this interaction. The I I/I OdC
appear to be a consequence of crystal packing. In line with
these observations, model compounds 6 and 8 reveal a lesser
degree of iodine polarization due to an electron donating para
substituent (ester linkage) in 6 and a meta-oriented substituent
in 8. Thus, computational results performed on simpler
analogues accurately reflect the relative halogen bonding
abilities of tritopic iodoarenes 1a-4a.
3 3 3 3 3 3
bifurcated synthon features an iodo group that functions as
both electron donor and acceptor and in this regard resembles
the halogens found in cyclic halogen bonding trimers reported
by Nangia22 and Bosch.23 In 1a and 3a, however, halogen
bonded chains rather than cyclic supramolecular constructs
are produced.
In an effort to better understand how the substitution
pattern of the haloarene units in 1-4 affects halogen polari-
zation, electrostatic potential maps were generated from DFT
calculations performed on simpler model compounds.16
Specifically, four iodoarenes 5-8 representing truncated ver-
sions of 1a-4a, respectively, were modeled. The molecular
conformation in each model compound was taken directly
from relevant crystal structure coordinates of 1a-4a in order
to approximate the empirically observed solid-state confor-
mation. Torsion angles about the ketone and ester linkages
were then fixed. The results of this computational study are
presented in Table 3. In each case a region of positive
electrostatic potential (blue) is located on the iodine substi-
tuent along the axis of the C-I bond; however, qualitative
differences in the degree of polarization as a function of arene
substitution pattern are also apparent. These differences are
quantified in a relative sense by the calculated potentials
shown at thebottomofTable 3. Ascanbe seen, the iodoarenes
possessing electron withdrawing carbonyl groups at the para
Conclusions
This study probed the propensity of structurally related but
electronically differentiated tritopic haloarenes to engage in
various types of solid-state halogen bonding. While only a
small number of structures were examined, the lack of corre-
lation between halogen bonding interactions among confor-
mationally flexible substrates that differed only in the identity
of the halogen highlights the difficulty in predicting the
occurrence and topology of these interactions, even in organic
molecules devoid of strong hydrogen bonding functionality.
The generally weak nature of many halogen bonding interac-
tions may contribute to this lack of predictabilityas solid-state
self-assembly processes that maximize alternative noncova-
lent attractions (e.g., C-H O hydrogen bonds, van der
3 3 3
Waals attractions) may offer greater energetic advantages.24
In contrast, the iodoarene derivatives 1a, 2a, and 3a all gave
rise to structures in which halogen bonding seemingly plays a

Article
Crystal Growth & Design, Vol. 10, No. 1, 2010 231
central role. Both 1a13 and 3a exhibit similar I I/I OdC
bifurcated motifs assisted by the electronic activation of the
(8) (a) Raatikainen, K.; Huuskonen, J.; Lahtinen, M.; Metrangolo, P.;
Rissanen, K. Chem. Commun. 2009, 2160–2162. (b) Metrangolo, P.;
Meyer, F.; Pilati, T.; Resnati, G.; Terraneo, G. Chem. Commun. 2008,
1635–1637. (c) Saha, B. K.; Jetti, R. K. R.; Reddy, L. S.; Aitipamula, S.;
Nangia, A. Cryst. Growth Des. 2005, 5, 887–899. (d) Saha, B. K.;
Nangia, A. CrystEngComm 2006, 8, 440–443. (e) Suss, H. I.; Hulliger,
J. Microporous Mesoporous Mater. 2005, 78, 23–27.
(9) Mele, A.; Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G.
J. Am. Chem. Soc. 2005, 127, 14972–14973.
(10) (a) Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.;
Zhu, W. J. Med. Chem. 2009, 52, 2854-2862 and references cited.
(b) Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Proc. Natl. Acad.
Sci. U. S. A. 2004, 101, 16789–16794.
3 3 3 3 3 3
iodine substituents by electron withdrawing para-carbonyl
groups, while trimesic acid ester 2a14 assembles via I OdC
3 3 3
and I π interactions to form nanoscale channel-type inclu-
3 3 3
sion complexes in the presence of suitable solvent templates.
Future studies will examine the occurrence of similar interac-
tions in more highly functionalized substrates.
Acknowledgment. We thank the University of Iowa for
financial support and G. P. Sharavathi for assistance with
compound characterization. N.P.R. thanks the U.S. National
Science Foundation for funding the purchase of an APEXII
diffractometer (CHE-0420497).
(11) Aakeroy, C. B.; Fasulo, M.; Schultheiss, N.; Desper, J.; Moore, C.
¨
J. Am. Chem. Soc. 2007, 129, 13772–13773.
(12) Dey, A.; Jetti, R. K. R.; Boese, R.; Desiraju, G. R. CrystEngComm
2003, 5, 248–252.
(13) Pigge, F. C.; Vangala, V. R.; Swenson, D. C. Chem. Commun. 2006,
2123–2125.
(14) Pigge, F. C.; Vangala, V. R.; Kapadia, P. P.; Swenson, D. C.; Rath,
N. P. Chem. Commun. 2008, 4726–4728.
(15) Elghamry, I. Synthesis 2003, 2301–2303.
Supporting Information Available: X-ray data with details of
refinement procedures (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(16) Spartan 02, Wave Function, Inc., www.wavefun.com.
(17) For a definition of this terminology, see: Pedireddi, V. R.; Reddy,
D. S.; Goud, B. S.; Craig, D. C.; Rae, A. D.; Desiraju, G. R.
J. Chem. Soc., Perkin Trans. 2 1994, 2353–2360.
(18) (a) Brammer, L.; Bruton, E. A.; Sherwood, P. Cryst. Growth Des.
2001, 1, 277–290. (b) van den Berg, J.-A.; Seddon, K. R. Cryst. Growth
Des. 2003, 3, 643–661. (c) Thalladi, V. R.; Weiss, H.-C.; Blaeser, D.;
Boese, R.; Nangia, A.; Desiraju, G. R. J. Am. Chem. Soc. 1998, 120,
8702–8710.
References
(1) Reviews of halogen bonding: (a) Metrangolo, P.; Resnati, G.
Science 2008, 321, 918–919. (b) Metrangolo, P.; Meyer, F.; Pilati, T.;
Resnati, G.; Terraneo, G. Angew. Chem., Int. Ed. 2008, 47, 6114–
6127. (c) Metrangolo, P.; Resnati, G.; Pilati, T.; Biella, S. Struct.
Bonding (Berlin) 2008, 126, 105–136. (d) Rissanen, K. CrystEng-
Comm 2008, 10, 1107–1113.
(2) (a) Lommerse, J. P. M.; Stone, A. J.; Taylor, R.; Allen, F. H. J. Am.
Chem. Soc. 1996, 118, 3108–3116. (b) Riley, K. E.; Merz, K. M. Jr.
J. Phys. Chem. A 2007, 111, 1688–1694. (c) Ramasubbu, N.;
Parthasarathy, R.; Murray-Rust, P. J. Am. Chem. Soc. 1986, 108,
4308–4314.
(3) (a) Riley, K. E.; Murray, J. S.; Politzer, P.; Concha, M. C.; Hobza,
P. J. Chem. Theory Comput. 2009, 5, 155-163 and references cited.
(b) Gavezzotti, A. Mol. Phys. 2008, 106, 1473–1485.
(19) Kumar, V. S. S.; Pigge, F. C.; Rath, N. P. Cryst. Growth Des. 2006,
6, 193–196.
(20) For discussion of X π interactions, see (a) Schollmeyer, D.;
3 3 3
Shishkin, O. V.; Ruhl, T.; Vysotsky, M. O. CrystEngComm
2008, 10, 715–723. (b) Swierczynski, D.; Luboradzki, R.;
Dolgonos, G.; Lipkowski, J.; Schneider, H.-J. Eur. J. Org. Chem.
2005, 1172–1177. (c) Prasanna, M. D.; Guru Row, T. N. Cryst. Eng.
2000, 3, 135–154.
ꢀ
(4) (a) Fourmigue, M.; Batail, P. Chem. Rev. 2004, 104, 5379–5418. (b)
(21) (a) Britton, D.; Brennessel, W. W. Acta Crystallogr. 2004, C60,
o552–o556. (b) Brock, C. P. Acta Crystallogr. 1987, C43, 1784–
1786. (c) Britton, D.; Young, V. G. Jr. Acta Crystallogr. 1997, C53,
1359–1362.
(22) See references 8c, 8d and Jetti, R. K. R.; Thallapally, P. K.;
Xue, F.; Mak, T. C. W.; Nangia, A. Tetrahedron 2000, 56, 6707–
6719.
Hanson, G. R.; Jensen, P.; McMurtrie, J.; Rintoul, L.; Micallef, A. S.
Chem.;Eur. J. 2009, 15, 4156–4164.
(5) Metrangolo, P.; Carcenac, Y.; Lahtinen, M.; Pilati, T.; Rissanen,
K.; Vij, A.; Resnati, G. Science 2009, 323, 1461–1464.
(6) Cariati, E.; Forni, A.; Biella, S.; Metrangolo, P.; Meyer, F.;
Resnati, G.; Righetto, S.; Tordin, E.; Ugo, R. Chem. Commun.
2007, 2590–2592.
(23) Bosch, E.; Barnes, C. L. Cryst. Growth Des. 2002, 2, 299–302.
(24) For a related discussion, see: Aakeroy, C. B.; Schultheiss, N.;
¨
(7) Prasang, C.; Nguyen, H. L.; Horton, P. N.; Whitwood, A. C.;
Bruce, D. W. Chem. Commun. 2008, 6164–6166.
Desper, J.; Moore, C. CrystEngComm 2007, 9, 421–426.