Charge-Assisted Halogen Bonding in Bromo- and Iodophenylpyridinium Chlorides

Article abstract of DOI:10.1021/acs.cgd.5b00835

Ten N-halophenylpyridinium salts (halogen = Br or I) with chloride (and in one case iodide) counterions have been prepared and structurally characterized in order to examine the degree of solid state halogen bonding exhibited in these systems. N-Halophenylpyridinium salts are easily synthesized from existing pyridines, and the cationic pyridinium group is expected to increase the halogen bond donor ability of attached halophenyl moieties. Halide anions functioning as halogen bond acceptors facilitate formation of charge-assisted halogen bonds. All five substrates featuring iodophenyl or diiodophenyl substituents displayed the expected halogen bonding interactions. In several cases halide ion acceptors were also engaged in complementary hydrogen bonding interactions with C-H groups of pyridinium rings and O-H groups of water solvates. Halogen bond donors containing a diiodophenyl group formed either an extended network or discrete supramolecular macrocyclic constructs through ArI...Cl^-...IAr bridging interactions. Significantly fewer and weaker halogen bonding interactions were observed in crystals of N-bromophenylpyridinium salts. The attenuation of halogen bonding in these substrates is attributed to the inability of the activated bromoarene halogen bond donors to compete with hydrogen bond donors (C-H/O-H residues) for the halide anion. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.cgd.5b00835

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ChargeꢀAssisted Halogen Bonding in Bromoꢀ and
Iodophenylpyridinium Chlorides
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Christopher J. Kassl, Dale C. Swenson, and F. Christopher Pigge*
Department of Chemistry, University of Iowa, Iowa City, IA, 52242
ABSTRACT: Ten Nꢀhalophenylpyridinium salts (halogen = Br or I) with chloride (and in one
case iodide) counterions have been prepared and structurally characterized in order to examine
the degree of solid state halogen bonding exhibited in these systems. NꢀHalophenylpyridinium
salts are easily synthesized from existing pyridines, and the cationic pyridinium group is
expected to increase the halogen bond donor ability of attached halophenyl moieties. Halide
anions functioning as halogen bond acceptors facilitate formation of chargeꢀassisted halogen
bonds. All five substrates featuring iodophenyl or diiodophenyl substituents displayed the
expected halogen bonding interactions. In several cases halide ion acceptors were also engaged
in complementary hydrogen bonding interactions with C–H groups of pyridinium rings and O–H
groups of water solvates. Halogen bond donors containing a diiodophenyl group formed either
an extended network or discrete supramolecular macrocyclic constructs through ArIꢁꢁꢁCl−ꢁꢁꢁIAr
bridging interactions. Significantly fewer and weaker halogen bonding interactions were
observed in crystals of Nꢀbromophenylpyridinium salts. The attenuation of halogen bonding in
these substrates is attributed to the inability of the activated bromoarene halogen bond donors to
compete with hydrogen bond donors (C–H/O–H residues) for the halide anion.
Cl
N
I
I
F. Christopher Pigge
Department of Chemistry
University of Iowa
Iowa City, Iowa 52242
Ph: 319ꢀ335ꢀ3805
Fax: 319ꢀ335ꢀ1270
Email: chrisꢀpigge@uiowa.edu
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ChargeꢀAssisted Halogen Bonding in Bromoꢀ and
Iodophenylpyridinium Chlorides
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Christopher J. Kassl, Dale C. Swenson, and F. Christopher Pigge*
Department of Chemistry, University of Iowa, Iowa City, Iowa, 52242, USA
ABSTRACT: Ten Nꢀhalophenylpyridinium salts (halogen = Br or I) with chloride (and in one
case iodide) counterions have been prepared and structurally characterized in order to examine
the degree of solid state halogen bonding exhibited in these systems. NꢀHalophenylpyridinium
salts are easily synthesized from existing pyridines, and the cationic pyridinium group is
expected to increase the halogen bond donor ability of attached halophenyl moieties. Halide
anions functioning as halogen bond acceptors facilitate formation of chargeꢀassisted halogen
bonds. All five substrates featuring iodophenyl or diiodophenyl substituents displayed the
expected halogen bonding interactions. In several cases halide ion acceptors were also engaged
in complementary hydrogen bonding interactions with C–H groups of pyridinium rings and O–H
groups of water solvates. Halogen bond donors containing a diiodophenyl group formed either
an extended network or discrete supramolecular macrocyclic constructs through ArIꢁꢁꢁCl−ꢁꢁꢁIAr
bridging interactions. Significantly fewer and weaker halogen bonding interactions were
observed in crystals of Nꢀbromophenylpyridinium salts. The attenuation of halogen bonding in
these substrates is attributed to the inability of the activated bromoarene halogen bond donors to
compete with hydrogen bond donors (C–H/O–H residues) for the halide anion.
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INTRODUCTION
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Halogen bonding interactions have emerged as important nonꢀcovalent attractions capable of
facilitating molecular recognition and selfꢀassembly events in both solution phase and the solid
state.1 For example, halogen bonding (XB) interactions have been utilized in the design of
numerous functional materials,2 as the principal recognition element of molecular hosts targeting
halocarbon and anionic guests,3 and as the operative feature in new organocatalysts.4 Likewise,
in the solid state designed XB interactions have been used to mediate selfꢀassembly of numerous
intriguing organic and inorganic crystalline materials.5,6 While XB remains much less exploited
in supramolecular chemistry compared to hydrogen bonding, halogen bonding clearly represents
an increasingly important design tool for control over a variety of nonꢀcovalent assembly
processes.
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The basis for halogen bonding is generally regarded as an electrostatic attraction between an
electrophilic halogen bond donor and a Lewis base (LB) halogen bond acceptor.7 Many
organohalogens feature an uneven distribution of electron density about the halogen such that a
region of positive electrostatic potential exists directly opposite the C–X bond axis.8 An
attractive interaction between this region of positive electrostatic potential and an electron rich
Lewis basic site constitutes a halogen bond. Much of what is known about the strength of
halogen bonds has been inferred from crystallographic studies in which halogen bonding is
indicated by XꢁꢁꢁLB distances shorter than the sum of the relevant van der Waals radii and C–
XꢁꢁꢁLB angles approaching 180°.1,7,8 Recently, several studies have examined the strength of
halogen bonding in solution by NMR spectroscopy.9
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Computational and experimental studies consistently show that organoꢀhalogen bond donor
ability follows the order RI > RBr > RCl as a consequence of increasing polarizability of the
heavier halogens.1,7,8 Importantly, carbon hybridization and electronꢀwithdrawing inductive
effects exerted by nearby substituents can further enhance XB donor ability of R–X groups.
Indeed, while relatively simple "unactivated" organohalogens are not particularly good XB
donors, iodoꢀalkynes, perfluoroꢀiodoalkanes, and perfluoroꢀiodoarenes are among the best
halogen bond donors.10 However, the ability to incorporate these activated halogen bonding
motifs into larger molecules with the aim of influencing selfꢀassembly via halogen bonding can
be difficult. Thus, the identification of additional synthetically accessible haloꢀorganic moieties
that exhibit structure directing effects as a consequence of reliable halogen bond donor ability
may further expand the role of halogen bonding in supramolecular chemistry and crystal
engineering.
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In formulating strategies to construct modular XB donors amenable to potential incorporation
into larger supramolecular building blocks, we were attracted to the use of pyridinium cations as
activating groups toward covalently attached haloaryl substituents. We reasoned that the
pyridinium substituent would serve as a potent electronꢀwithdrawing group to activate the
attached halophenyl moieties. Moreover, Nꢀhalophenyl pyridinium cations should be easily
accessed via manipulation of preꢀexisting pyridine rings. In turn, any molecule possessing a
peripheral pyridine substituent might then be converted to a potential XB donor. Notably, the
superior XB donor ability of cationic iodoꢀ and bromoꢀazolium salts (e.g., halopyridinium and
haloimidazolium salts) has been amply demonstrated in a number of studies.3cꢀi,4,9a,11 The
cationic halogen bond donors envisioned in this study, however, differ from halopyridinium
donors in that the halogen is not directly attached to the pyridine ring, but instead is present on
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an Nꢀaryl moiety. Indirect support for the notion of Nꢀhalophenylpyridinium derivatives as XB
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donors can be found in studies examining solid state halogen bonding interactions in positively
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+
charged haloanilinium salts (i.e., XC6H4NH3 ).12 Notably, the presence of a competitive
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+
hydrogen bond donating group in the form of the NH3 fragment is a complicating factor in these
studies. The Nꢀhalophenylpyridinium derivatives investigated in this this study lack such potent
Hꢀbond donors. Further evidence for halogen bonding activating effects of pyridinium cations
can be found in solid state structures of bis(halobenzyl)bipyridinium and
bis(halophenyl)imidazolium salts.13
We describe below results of a preliminary investigation probing the halogen bonding
behavior of nine iodophenylꢀ and bromophenylpyridinium chlorides (Chart 1). Both monoꢀ and
dihalophenylpyridinium chlorides have been structurally characterized to assay the propensity
for formation of discrete chargeꢀassisted XꢁꢁꢁCl− halogen bonds as well as bridging XꢁꢁꢁCl−ꢁꢁꢁX
interactions leading to extended solid state networks with chloride anions functioning as XB
acceptors in each case. One substrate (5) was obtained in crystalline form as the iodide salt, and
structural details of this material are also presented.
Chart 1. Nꢀhalophenylpyridinium chlorides structurally characterized in this study.
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EXPERIMENTAL SECTION
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General procedure for the preparation of N-halophenylpyridinium salts
The route is outlined in Scheme 1. Zincke salt 1114 (0.5 mmol) and the appropriate haloaniline
(0.75 mmol) were combined along with 5.0 mL of nꢀbutanol in a 10 mL round bottom flask. The
mixture was heated to reflux with stirring under Ar and maintained for 3 d. After this time
analysis of the reaction mixture by LRMS indicated complete disappearance of Zincke salt 11.
The solvent was evaporated under reduced pressure and the crude material was dissolved in a
minimum amount of methanol and added dropwise to a solution of diethyl ether (200 mL). The
resulting precipitate was collected by filtration and washed sequentially with diethyl ether and
ethyl acetate until washings became clear in color, and then dried under vacuum.
The salts are all insoluble in most organic solvents, but exhibit good solubility in methanol and
nꢀbutanol. They are sparingly soluble in acetone and water.
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X-ray Crystallography
Single crystals of Nꢀhalophenylpyridinium salts 1-10 were grown by dissolving 5 mg of the
salt in ~1 mL of an acetone:methanol solution (1:1) inside a 20ꢀmL borosilicate glass screw cap
scintillation vial. After 1ꢀ2 days of slow solvent evaporation at room temperature, crystals
suitable for single crystal Xꢀray diffractometry were obtained.
Diffraction data were collected on a Nonius Kappa CCD diffractometer equipped with Mo Kα
radiation with λ = 0.71073 Å. Crystallographic data is shown in Tables 1 and 2. Select details on
structure solution and refinement are described below and full details can be found in the
Supporting Information (CIF).
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10•(H2O)~1.5. The structure contains two sites partially occupied by chloride counterion and
water solvate. One site (O3ꢀCl7) was refined to 0.671(4) occupancy while the other site (O4ꢀCl6)
refined to 0.571(8) occupancy. Atoms in each respective site were modeled with the same
anisotropic displacement parameters. Hydrogen bond distances to O1 and O2A were restrained
to 0.85 Å. The position of hydrogen atoms bonded to O4 was not successfully modeled but their
presence is inferred.
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N-4-Iodophenylpyridinium chloride (1)
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Yield: 77% as light brown powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.24 (d, 2H,
J = 6.9 Hz), 8.79 (t, 1H,), 8.30 (dt, 2H), 8.12 (d, 2H, J = 6.9 Hz), 7.60 (d, 2H, J = 6.9 Hz). 13C
NMR (d4ꢀMeOH, 75 MHz) δ: 148.2, 146.0 141.0, 129.6, 127.3, 98.8. HRMS (ESI): 281.9780
calculated for C11H9NI [M]+: found 281.9785.
N-4-Bromophenylpyridinium chloride (2)
1
Yield: 73% as creamꢀcolored powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.32 (d,
2H, J = 6.9 Hz), 8.86 (t, 1H), 8.35 (dt, 2H), 7.98 (d, 2H, J = 6.9 Hz), 7.84 (d, 2H, J = 6.9 Hz).
13C NMR (d4ꢀMeOH, 75 MHz) δ: 148.2, 146.1, 142.5, 134.8, 129.6, 127.5 127.0. HRMS (ESI):
233.9918 calculated for C11H9NBr [M]+; found 233.9923.
N-3-Iodophenylpyridinium chloride (3)
1
Yield: 85% as light brown powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.24 (d, 2H,
J = 6.0 Hz), 8.80 (t, 1H), 8.31ꢀ8.26 (m, 3H), 8.12 (d, 1H, J = 8.1 Hz), 7.85 (d, 1H, J = 8.1 Hz),
7.50 (t, 1H). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 148.3, 146.1, 142.0, 134.5, 133.0, 129.6, 125.2,
95.4. HRMS (ESI): 281.9780 calculated for C11H9NI [M]+; found 281.9788.
N-3-Bromophenylpyridinium chloride (4)
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Yield: 63% as light yellow powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.26 (d, 2H,
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J = 6.9 Hz), 8.86 (t, 1H), 8.35 (t, 2H), 8.14 (d, 1H, J = 2.1 Hz), 7.96 (d, 1H, J = 8.1 Hz), 7.87
(dd, 1H), 7.68 (t, 1H). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 149.7, 147.5, 142.5, 137.1, 134.5,
130.9, 130.2, 126.1, 125.8. HRMS (ESI): 233.9918 calculated for C11H9NBr [M]+; found
233.9922.
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N-2-Iodophenylpyridinium iodide (5)
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Yield: 38% as dark brown powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.20 (d, 2H,
J = 6.0 Hz), 8.91 (t, 1H), 8.41 (t, 2H), 8.26 (d, 1H, J = 8.1 Hz), 7.82 (m, 2H), 7.53 (t, 1H). 13C
NMR (d4ꢀMeOH, 75 MHz) δ: 148.0, 146.3, 138.9, 135.5, 134.5, 131.0, 129.7, 128.6, 98.3.
HRMS (ESI): 281.9780 calculated for C11H9NI [M]+; found 281.9783.
N-2-Bromophenylpyridinium chloride (6)
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Yield: 68% as bright yellow powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.18 (d,
2H, J = 6.9 Hz), 8.86 (t, 1H), 8.35 (t, 2H), 7.97 (t, 1H), 7.86 (d, 1H, J = 8.1 Hz), 7.96 (d, 1H, J =
8.1Hz), 7.76ꢀ7.64 (m, 2H). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 149.3, 147.7, 137.4, 135.5, 134.6,
130.8, 129.7, 128.9, 115.7. HRMS (ESI): 233.9918 calculated for C11H9NBr [M]+; found
233.9926.
N-2,4-Diiodophenylpyridinium chloride (7)
1
Yield: 32% as dark brown powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.15 (d, 2H,
J = 6.1 Hz), 8.91 (t, 1H), 8.58 (d, 1H, J = 2.4 Hz), 8.38 (t, 2H), 8.11 (dd, 1H), 7.56 (d, 1H, J =
8.1Hz). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 148.1, 146.1, 139.3, 128.4, 127.8, 98.1, 94.8. HRMS
(ESI): 407.8746 calculated for C11H8NI2 [M]+; found 407.8754.
N-2,4-Dibromophenylpyridinium chloride (8)
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Yield: 71% as light yellow powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.17 (d, 2H,
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J = 6.0 Hz), 8.89 (t, 1H), 8.36 (t, 2H), 8.13 (d, 1H, J = 2.1 Hz), 7.92 (dd, 1H), 7.77 (d, 1H, J =
8.1 Hz). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 149.6, 147.7, 137.8, 134.0, 130.1, 129.7, 127.6,
115.7. HRMS (ESI): 311.9024 calculated for C11H8NBr2 [M]+; found 311.9034.
4-Phenyl-N-2,4-diiodophenylpyridinium chloride (9)
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Yield: 34% as dark brown powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.13 (d, 2H,
J = 6.1 Hz), 8.71 (d, 2H, J = 6.1 Hz), 8.65 (d, 1H, J = 2.1 Hz), 8.20 (m, 3H), 7.77 (m, 3H), 7.60
(d, 1H, J = 8.1 Hz). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 149.6, 147.3, 144.4, 140.6, 139.5, 134.8,
134.3, 131.2, 129.6, 129.3, 126.1, 98.2, 94.8. HRMS (ESI): 483.9059 calculated for C17H12NI2
[M]+; found 483.9071.
4-Phenyl-N-2,4-dibromophenylpyridinium chloride (10)
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Yield: 44% as light yellow powder; mp: >2200C. H NMR (d4ꢀMeOH, 300 MHz) δ: 9.10 (d, 2H,
J = 6.9 Hz), 8.65 (d, 2H, J = 6.9 Hz), 8.26 (d, 1H, J = 2.1 Hz), 8.12 (d, 2H, J = 8.7 Hz), 7.95 (dd,
1H), 7.77 (d, 1H, J = 8.1 Hz), 7.69ꢀ7.71 (m, 3H). 13C NMR (d4ꢀMeOH, 75 MHz) δ: 147.3,
142.5, 137.8, 134.8, 134.2, 134.1, 133.0, 131.2, 130.3, 129.7, 127.5, 126.1, 120.7. HRMS (ESI):
387.9332 calculated for C17H12NBr2 [M]+; found 387.9339.
Table 1. Crystallographic data for Nꢀhalophenylpyridinium salts 1ꢀ5.
1•(H2O)2
Crystallizatio 88
2•(H2O)1.5
3•(H2O)0.5
4•(H2O)0.5
5
85
89
83
77
n Yield (%)
Formula
C11H13ClIN
O2
C11H12BrClNO C11H10ClINO0 C11H10BrClNO C11H9I2N
1.5
.5
0.5
Formula
weight
353.57
297.58
326.56
279.35
408.99
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Crystal
system
monoclinic
monoclinic
tetragonal
triclinic
monoclinic
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7
8
9
Space group P21/c
P21/n
P41212
8.3557(6)
8.3557(6)
34.1012(3)
90
Pꢀ1
P21/c
a/Å
b/Å
c/Å
α/0
8.9791(5)
7.4795(4)
17.0693(12)
7.4556(5)
7.4154(4)
11.0476(6)
13.9173(8)
102.3083(14)
95.2744(13)
13.6280(14)
6.9633(7)
13.4276(13)
90
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19.7533(11) 19.5710(13)
90 90
96.2197(12) 102.9486(17)
β/0
90
102.5700(1
2)
γ/0
90
90
90
90.0762(12)
1108.97
4
90
V/Å3
1318.8(2)
4
2427.3(5)
8
2380.9
8
1243.69(15)
4
Z
Dcalc
µ (mmꢀ1)
T/K
1.781
2.617
190(2)
1.629
3.586
190(2)
38104
1.822
2.887
190(2)
41165
1.674
2.184
5.021
190(2)
16298
3.918
190(2)
13789
No.
of 17377
reflections
No.
of 2507
5214
4029
3373
3207
5120
4425
2294
2014
unique
reflections
No.
of 2357
reflections
with I > 2σ
(I)
No.
of 161
304
136
265
127
params.
R1 [I > 2σ 0.0257
(I)]
0.0293
0.0178
0.0254
0.0372
wR2
0.0955
0.1028
0.0464
0.0923
0.1273
CCDC No.
1052260
1052261
1052262
1052263
1052264
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Table 2. Crystallographic data for Nꢀhalophenylpyridinium salts 6ꢀ10.
5
6
7
6•(H2O)
7•(H2O)1.5
8•(H2O)2
9
10•(H2O)~1.5
8
9
Crystallizati 80
73
90
75
86
10
11
12
13
14
15
16
17
18
19
20
21
22
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on
(%)
yield
Formula
C11H11BrCl
NO
288.56
C11H11ClI2N
O1.5
470.46
C11H12Br2ClN C17H12ClI2 C17H13.39Br2Cl1.11N
O2
N
O0.89
Formula
weight
385.49
519.53
445.15
Crystal
system
monoclinic
monoclinic
monoclinic
monoclini triclinic
c
Space group P21/n
C2/c
P21/c
C2/c
Pꢀ1
a/Å
b/Å
8.4925(11)
9.9455(13)
31.759(2)
9.0729(7)
10.4651(5)
8.5805(3)
9.2519(4) 9.9620(6)
19.9679(1 11.8679(13)
0)
c/Å
13.5872(19) 19.9453(14)
16.0117(7)
19.1621(9 16.181(2)
)
α/0
90
90
90
90
99.712(2) 98.300(6)
90 105.069(6)
3489.3(4) 1705.9(4)
107.803(6)
β/0
90.684(3)
90
90.4430(13)
90
107.987(2)
90
γ/0
V/Å3
Z
1147.5(5)
4
5747.1(12)
16
1367.52(15)
4
8
4
Dcalc
µ (mmꢀ1)
T/K
1.670
3.786
190(2)
2.175
4.544
190(2)
1.872
6.112
190(2)
2.008
3.755
190(2)
1.719
4.908
190(2)
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9
No.
reflections
No.
unique
reflections
No.
of 15431
of 2105
35759
6940
22401
3280
19769
3343
19097
6202
of 1422
I >
5855
307
2767
155
2923
192
2698
417
10
11
12
13
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reflections
with
2σ(I)
No.
of 144
params
R1 [I > 2σ 0.0434
(I)]
0.0255
0.0311
0.0366
0.0653
wR2
0.1210
0.0811
0.1028
0.1241
0.1674
CCDC No.
1052265
1052266
1052267
1052268
1052269
RESULTS AND DISCUSSION
The synthesis of halophenylpyridinium halides 1ꢀ10 was accomplished using the general
route illustrated in Scheme 1. Pyridine and 4ꢀphenylpyridine were converted to the
corresponding Zincke salts 11 in good yield by treatment with 1ꢀchloroꢀ2,4ꢀdinitrobenzene
according to published procedures.14 Simply heating 11 with the appropriate haloꢀ or
dihaloaniline in nꢀBuOH afforded the desired halophenylpyridinium chlorides 1ꢀ4 and 6ꢀ10 in
moderate to good isolated yields.15 Initial attempts to prepare these materials in a lower boiling
solvent (EtOH) were unsuccessful, and in one case an intermediate arising from pyridine ring
opening was obtained.16 In the reaction of 11 with 2ꢀiodoaniline, the desired Nꢀ(2ꢀ
iodophenyl)pyridinium cation was obtained as the iodide salt. Evidently, the iodoaniline and/or
a portion of the 2ꢀiodophenylpyridinium cation suffered deꢀhalogenation under the reaction
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conditions to provide the iodide anions observed in the crystalline salts. None of the other
substrates exhibited any evidence of similar deꢀhalogenation processes. Each salt was
7
8
9
1
spectroscopically characterized by H/13CꢀNMR and positive ion ESIꢀHRMS. In each case Xꢀ
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ray quality single crystals were grown by slow evaporation of mixed MeOH/acetone solutions.
Crystalline samples were characterized by singleꢀcrystal Xꢀray diffractometry and PXRD.
Scheme 1. Route used to prepare Nꢀhalophenylpyridinium salts 1ꢀ10.
At the outset, we expected the electronꢀwithdrawing pyridinium substituents to activate
halophenyl groups toward halogen bonding to varying degrees according to the identity of the
halogen (Br versus I) and substitution pattern (o, m, p). The ability of halide anions (e.g., Cl−) to
serve as halogen bond acceptors is wellꢀdocumented, so it was further expected that any halogen
bonding observed would be of the chargeꢀassisted variety.1e,3c,17 While substrates 1ꢀ10 are
devoid of conventional hydrogen bond donors, we recognized that solid state aryl and pyridinium
C–HꢁꢁꢁX− hydrogen bonding may be competitive with halogen bonding. Additionally, solubility
features of 1ꢀ10 required use of polar solvent mixtures in crystallization experiments and so the
potential presence of hydrogen bonding solvates (methanol, adventitious H2O) was also a
complicating feature.
The structure of 4ꢀiodophenylpyridinium chloride (1) embodies many of the considerations
outlined above. The ion pair 1 and two water molecules of solvation comprise the asymmetric
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unit (Figure 1). A halogen bonding interaction is clearly evident as indicated by the ratio of the
observed IꢁꢁꢁCl− distance (3.436 Å) over the sum of the relevant van der Waals radii (3.79 Å):
RXB = 0.91.18 Additionally, the C–IꢁꢁꢁCl− angle is close to linear (166.27º) and the metrics of this
XB interaction are similar to those observed in the structure of 4ꢀiodoanilinium chloride reported
previously.12b The two water molecules are engaged with the Cl− ion via hydrogen bonding and
are part of an extensive network of solvated chloride ions as shown in Figure 2. Hydrogen
bonding between chloride ions and water solvates produces fused cyclic motifs linked by
iodophenylpyridinium cations via IꢁꢁꢁCl− halogen bonding and pyridinium C–HꢁꢁꢁOH2 hydrogen
bonding to give 2D layers. Iodophenylpyridinium cations are stacked in a headꢀtoꢀtail manner
consistent with favorable dipolar alignment. Centroid–centroid distances between stacked
iodophenyl and pyridinium rings are within range of π−π interactions (3.783 Å). The layers
evident in Figure 2 stack in slightly offset fashion and are linked by additional C–HꢁꢁꢁCl−
hydrogen bonding (see Figure S1 in the Supporting Information). Thus, the overall packing
features segregated stacks of 4ꢀiodophenylpyridinium cations separated by channelꢀtype
networks of solvated chloride ions (Figure S2).19
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Figure 1. Asymmetric unit in 1. Chloride anion shown as green sphere. IꢁꢁꢁCl− d = 3.436 Å,
RXB = 0.91, C–IꢁꢁꢁCl− = 166.27º.
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Figure 2. Interplay of XB and chloride ion solvation in 1.
The structure of 4ꢀbromophenylpyridinium chloride (2) differs from the iodo analogue in
several ways. Firstly, two unique pyridinium cations are present in the asymmetric unit. Only
one of these is engaged in BrꢁꢁꢁCl− halogen bonding, and the BrꢁꢁꢁCl− distance (3.490 Å, RXB
=
0.95) is indicative of a relatively weak interaction (Figure 3). The aryl bromide of the second
cation participates in a bifurcated interaction in which the bromine functions as a halogen bond
donor to a water solvate molecule (BrꢁꢁꢁO 3.271 Å, RXB = 0.97, C–BrꢁꢁꢁO angle 163.53º) and a
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hydrogen bond acceptor to a pyridinium CꢀH donor (HꢁꢁꢁBr distance 3.016 Å, C–BrꢁꢁꢁH angle
142.36º). Similar to the structure of 1, the chloride ions are present as part of cylic hydrated
networks linked by bridging bromophenyl pyridinium cations (through BrꢁꢁꢁCl−/OH2 halogen
bonding and pyridinium C–HꢁꢁꢁCl−/OH2 hydrogen bonding) to form 2D layers. In turn, these
layers are arranged in an offset fashion to afford stacks of pyridinium cations separated by
hydrated choride ion networks (Figure S5, very similar to the overall packing observed in 1).
Within individual stacks the aryl pyridinium cations adopt a favorable dipolar alignment with
arene – arene separations ranging from 3.786 Å to 3.914 Å.
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Figure 3. Halogen and hydrogen bonding interactions in 2. See text for XB and HB metrics.
The structure of 3ꢀiodophenylpyridinium chloride (3) features one ion pair and 0.5 H2O
solvate in the asymmetric unit. Each chloride anion exhibits six intermolecular contacts, one of
which is a relatively strong halogen bond to an iodoarene moiety (IꢁꢁꢁCl− distance 3.249 Å, RXB
=
0.86, C–IꢁꢁꢁCl− angle 168.01º). Aryl and pyridinium C–HꢁꢁꢁCl− hydrogen bonds from four
additional pyridinium cations and a hydrogen bond from a chlorideꢀbridging water molecule
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complete the coordination sphere of the anion (Figure 4). The overall packing in the crystal is
quite complicated, and the arylpyridinium cations are not engaged in intermolecular stacking
interactions as was observed in 1 and 2 (see Figure S6). Nonetheless, a notable feature of this
structure is the presence of relatively strong halogen bonding interactions that involve each
iodoarene group. Notably, these IꢁꢁꢁCl– interactions are shorter than those observed in the
structure of 1 (vide supra) and in a related 4ꢀiodoanilinium chloride salt.12b
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Figure 4. Intermolecular interactions of chloride ions in 3.
In contrast, the structure of the 3ꢀbromophenylpyridinium analogue (4) exhibits significantly
fewer halogen bonding interactions. Indeed, as found in the structure of 2, two unique ion pairs
are present in the asymmetric unit (along with a water of solvation), and only one of these
bromophenyl moieties is involved in halogen bonding to a chloride anion (labeled Br2A in
Figure 5). Furthermore, the metrics of this interaction (BrꢁꢁꢁCl− distance 3.543 Å, RXB = 0.97, C–
BrꢁꢁꢁCl− angle 161.13°) indicate a relatively weak halogen bond. The second bromophenyl unit
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(Br1) does not appear to participate in any significant intermolecular contacts. As was the case
in the structure of 3, chloride ions in 4 are organized in pairs through hydrogen bonding to a
bridging water molecule, and each anion exhibits a roughly octahedral coordination sphere
defined by O–H and C–H hydrogen bond donors, along with the single BrꢁꢁꢁCl− halogen bond. A
further feature of this structure is the selfꢀassembly of unique pyridinium cations into distinct
linear chains via dipolar stacking of pyridinium and bromophenyl rings (Figure S7).
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Figure 5. Coordination environment of chloride ions in 4.
The 2ꢀiodophenylpyridinium cation was found to crystallize with an iodide counterion (vide
supra). Crystals of 5 were additionally obtained free of water solvate molecules, perhaps as a
consequence of the increased hydrophobicity of iodide compared to chloride.20 The asymmetric
unit consists of one ion pair, and each iodoarene group is engaged in halogen bonding to an
iodide anion (Figure 6, C–IꢁꢁꢁI− 3.576 Å, RXB = 0.86, 170.47°). This interaction is considerably
shorter halogen bonds observed in crystals of 3ꢀiodoanilinium iodide reported by Gray and Jones
(3.691 Å).12a Each iodide anion exhibits six close intermolecular contacts. In addition to the
halogen bond, four C–HꢁꢁꢁI− hydrogen bonds are observed involving four different pyridinium
cations. C–H groups on pyridinium rings serve as Hꢀbond donors for three of these interactions,
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and the fourth emanates from an iodophenyl C–H donor. Distances of these interactions range
from 2.855 Å to 3.141 Å (I−ꢁꢁꢁH vdW distance = 3.26 Å). Each anion also approaches the face of
a nearby cationic pyridinium ring (d = 3.669 Å) to complete the iodide coordination sphere. A
view of the extended packing reveals that the iodide anions are well separated (closest I−ꢁꢁꢁI−
approach is > 6 Å) and reside in channels extending down the c axis (Figure S8).21
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Figure 6. ArIꢁꢁꢁI− halogen bonding and the coordination sphere around iodide in 5 (iodide anions
shown as purple spheres).
The structure of 2ꢀbromophenylpyridinium chloride (6) features little to no halogen bonding.
Instead, chloride anions are organized in zigꢀzag chains mediated by hydrogen bonding to
bridging water solvate molecules. Additional interactions involving pyridinium C–HꢁꢁꢁCl−
hydrogen bonding are also evident as illustrated in Figure 7. The distance of the BrꢁꢁꢁCl− contact
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shown in Figure 7 (light blue) is virtually equal to the sum of the van der Waals radii (d = 3.626
Å, ΣvdW radii = 3.66 Å, RXB = 0.99) and the C–BrꢁꢁꢁCl− angle is 158.02°. According to these
metrics, this interaction can, at best, be described as only a very weak halogen bond.
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Figure 7. Nonꢀcovalent interactions surrounding the chloride ion in 6. "Halogen bond"
indicated in light blue is equal to the sum of the BrꢁꢁꢁCl− vdW radii.
The dihalophenylpyridinium chlorides 7ꢀ10 were chosen for study to explore generation of
halogen bondꢀmediated networks. The introduction of a second halogen substituent in these
substrates produces an excess of halogen bond donors relative to chloride halogen bond
acceptors. Hence, the chloride ions may engage in halogen bonding with multiple halogen bond
donors to produce extended networks and/or 0D oligomers (e.g., dimers, trimers, etc).3c Indeed,
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the diiodophenylpyridinium derivatives 7 and 9 do, in fact, exhibit this solid state behavior, and
these structures are discussed together below, followed by structural descriptions of
dibromophenyl analogues 8 and 10.
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The asymmetric unit of diiodophenylpyridinium salt 7 contains two unique ion pairs and three
water molecules of solvation. In the extended packing the unique arylpyridinium chlorides are
segregated into individual, albeit similar, helical constructs mediated by bridging ArIꢁꢁꢁCl−ꢁꢁꢁIAr
halogen bonds. The metrics of halogen bonding interactions vary slightly between the two
helices (see Figure 8) and the aryl–pyridinium torsion angles differ by ~10°. Each halogen bond
indicated in Figure 8 approaches linearity with C–IꢁꢁꢁCl− angles ranging from 172.02° to 177.22°.
The chloride ions bridge a 4ꢀiodo substituent from one pyridinium cation and a 2ꢀiodo
substituent from a second pyridinium cation. The IꢁꢁꢁCl−ꢁꢁꢁI angles are similar in both helical
subunits (I1ꢁꢁꢁClꢀꢁꢁꢁI4 = 72.79° and I2ꢁꢁꢁClꢀꢁꢁꢁI3 = 75.95°). The two unique helical assemblies are
linked by a network of bridging water molecules that connect chloride ions from one helix with
chloride ions from the second helix (Figure 9). Aromatic C–HꢁꢁꢁCl− hydrogen bonding involving
the most polarized pyridinium hydrogen atoms (adjacent to the nitrogen) also aid in mediating
entanglement of the two helical networks.
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Figure 8. Extended halogen bonding networks in helical assemblies found in 7. Helices derived
from unique diiodophenylpyridinium cations are color coded red and grey. Halogen bonding
metrics: I1ꢁꢁꢁCl6A− = 3.140 Å (RXB = 0.83), I4ꢁꢁꢁCl6A− = 3.563 Å (RXB = 0.94), C–I1–Cl6A− =
173.69º, C–I4–Cl6A− = 172.06º, I2ꢁꢁꢁCl5A− = 3.230 Å (RXB = 0.85), I3ꢁꢁꢁCl5A− = 3.318 Å (RXB
0.88), C–I2–Cl5A− = 176.37º, C–I3–Cl5A− = 177.22º.
=
Figure 9. Bridging of unique helices in 7 through chloride ions by water solvates and C–HꢁꢁꢁCl−
hydrogen bonding.
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9
The diiodophenylꢀ4ꢀphenylpyridinium salt 9 also exhibits a halogen bonding network
composed of ArIꢁꢁꢁCl−ꢁꢁꢁIAr bridging interactions. In this structure, however, no solvate
molecules are found, perhaps a consequence of increased hydrophobicity upon introduction of
the 4ꢀphenyl substituent. Additionally, the halogen bonding network in this structure does not
produce infinite chains of ion pairs, but instead results in formation of discrete halogenꢀbonded
dimers that are arrayed in 2D layers (Figure 10).22 The supramolecular macrocycles formed as a
consequence of XBꢀmediated dimerization feature two distinct and relatively strong halogen
bonds (I1ꢁꢁꢁCl = 3.232 Å, RXB = 0.85, 169.39° and I2ꢁꢁꢁCl = 3.101 Å, RXB = 0.82, 172.63°), and
the IꢁꢁꢁCl−ꢁꢁꢁI angle is 81.44°. These halogen bonding metrics are comparable to those observed
in XBꢀmediated macrocycles assembled from ammonium or phosphonium chlorides and the
activated halogen bond donor 1,3,5ꢀtrifluoroꢀ2,4,6ꢀtriiodobenzene.22c The Cl−ꢁꢁꢁCl− separation
across the halogen bonded dimers is 10.788 Å. Halogen bonded dimers are arrayed in the bc
plane and are connected via pyridinium C–HꢁꢁꢁCl− hydrogen bonding (d = 2.575 Å) and dipoleꢀ
assisted stacking interactions between the 4ꢀphenyl substituents (πcentꢁꢁꢁπcent d = 3.879 Å).
Halogen bonded layers in the bc plane are stacked in an ABAB pattern and are linked through
additional C–HꢁꢁꢁCl− and C–HꢁꢁꢁI hydrogen bonding as shown in Figure 11. It should be noted
that 7 and 9 possess an identical array of XB donor groups (2,4ꢀdiiodophenylpyridinium) and
identical XB acceptors (Cl−), yet they exhibit much different halogen bonding networks. Thus,
the presence of water solvate molecules in 7 and their absence in 9 appears to critically influence
the observed halogen bonding motifs. Future research will examine the transferability of the
chlorideꢀbridged dimer synthon observed in 9 to other structurally related hydrophobic
diiodophenylpyridinium derivatives.
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Figure 10. Halogen bonded macrocyclic dimers observed in 9. See text for XB metrics.
Figure 11. Stacking of layers shown in Figure 10 in an ABA fashion.
The structure of Nꢀdibromophenylpyridinium salt 8 differs markedly from its diiodo analogue
7 in both crystalline network topology and degree of halogen bonding. Indeed, only the 2ꢀbromo
substituent of each phenylpyridinium cation exhibits any sort of halogen bonding interaction
(involving a neighboring arene ring rather than the chloride anion, Figure 12), while the 4ꢀbromo
substituent does not engage in any significant intermolecular contacts. Each chloride accepts
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two C–H hydrogen bonds from surrounding pyridinium rings. The remainder of the chloride
coordination sphere is occupied by hydrogen bonding to water solvate molecules, in turn leading
to an extensive network of waterꢀbridged chlorides. Solvated chloride ions are segregated in
alternating layers with the phenylpyridinium cations to produce an extended structure with wellꢀ
defined hydrophilic and hydrophobic regions (Figure S11).
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Figure 12. Environment around chloride ions in 8 and the absence of BrꢁꢁꢁCl− halogen bonds.
In contrast, certain solid state features found in the crystal structure of 10 bear similarity to
features found in the diiodo analogue 9 discussed above, but important differences are also
apparent. Most notably, each chloride ion in 10 is associated with a water of solvation, whereas
the structure of 9 is solvateꢀfree. The presence of solvated chloride ions gives rise to waterꢀ
bridged chloride dimers mediated by O–HꢁꢁꢁCl− hydrogen bonding. Halogen bonding from
bromoarene groups to both H2O and Cl− components of these dimers generate supramolecular
macrocyclic assemblies of dibromophenylpyridinium cations that superficially resemble the
chlorideꢀbridged macrocycles observed in the structure of 9 (except for the participation of water
solvate molecules). In these assemblies, the 2ꢀbromo substituent engages a chloride ion in
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halogen bonding (d = 3.286 Å, RXB = 0.90, C–BrꢁꢁꢁCl− = 175.92°) while the 4ꢀbromo substituent
interacts with a Lewis basic oxygen of H2O (BrꢁꢁꢁO d = 3.040 Å, RXB = 0.90, C–BrꢁꢁꢁO =
167.94º) (Figure 13). Chloride ions exhibit additional C–HꢁꢁꢁCl− contacts to phenylpyridinium
cations to extend the structure into three dimensions. The asymmetric unit of 10 contains a
second ion pair along with an associated water of solvation. Chloride ions are arrayed in a zigꢀ
zag chain mediated by hydrogen bonding water molecules. Positional disorder between the
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chloride ions and water molecules, however, is
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complicating feature.
Dibromophenylpyridinium cations are positioned about the H2O/Cl− chain and engage in both
halogen bonding and C–HꢁꢁꢁCl−/O hydrogen bonding (Figure S12). These two distinct networks
are then arranged in undulating parallel layers in the extended packing (see Figure S13).
Figure 13. Principal hydrogen/halogen bonding network in 10.
This study was initiated with the aim of assessing the feasibility of halophenylpyridinium
groups to engage in significant halogen bonding with halide anion XB acceptors, and to further
probe the utility of these interactions in mediating formation of discrete halogen bonding
networks when the XB donor:acceptor ratio = 2. In this context comparison of the
iodophenylpyridinium salts with their bomophenyl analogues reveals significant differences in
the type, extent, and magnitude of solid state XB interactions. Specifically, every iodoarene
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group in the substrates examined participates in solid state halogen bonding with chloride (or
iodide in 5) anions. This was largely anticipated as the activated iodoarenes are the sole halogen
bond donors in these substrates and the halide anions are the best halogen bond acceptors.23 The
observed ArIꢁꢁꢁX− interactions all exhibit RXB of ~ 0.90 or less and C–IꢁꢁꢁX− angles close to 180º.
In contrast, several structures incorporating bromophenylpyridinium cations feature ArBr
residues that do not engage in any significant intermolecular contacts. Moreover, in cases where
ArBrꢁꢁꢁCl− contacts are evident, the BrꢁꢁꢁCl− RXB are frequently only 0.99 – 0.95 (the structure of
10 providing an exception to this trend). Thus, while Nꢀiodophenylpyridinium cations appear to
be reliable halogen bond donors toward chloride and iodide anion acceptors, the analogous
interaction between Nꢀbromophenylpyridinium cations and chloride anions appears to be much
less significant.
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Differences in the interplay between halogen bonding and solvation as a function of halogen
bond donor are also evident. Chloride anions possess relatively high energies of solvation, so it
is not surprising that many of the salts examined in this study crystallize as hydrates (especially
given the hydrophilic solvents used to grow crystals). Nonetheless, the presence of chlorideꢀ
coordinated hydrate molecules proved compatible with halogen bonding to activated iodoarenes.
Many of the activated bromoarene XB donors examined, however, were only marginally
competitive with H2O (and C–H) hydrogen bond donors for the chloride anions. A good
example of this dichotomy is found through comparison of structures 7 and 8. In the former,
water solvates and ArIꢁꢁꢁCl− halogen bonding act in a complementary fashion to reinforce the
observed crystalline supramolecular network, while in the latter chargeꢀassisted halogen bonding
is completely absent in favor of chloride–Hꢀbonding contacts (despite similar degrees of
solvation in the two structures). In the future, it will be interesting to examine the effect that
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incorporation of Hꢀbond donors into iodophenylpyridinium frameworks has on solid state
interactions and halogen bonding. Based on the results of this study and the structure of 4ꢀ
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IC6H4NH3 Clꢀ reported previously by Rissanen and coꢀworkers,12b halogen and hydrogen
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bonding to anionic XB acceptors may be capable of acting in concert to influence
supramolecular assembly in a potentially predictable fashion.
A cationic pyridinium ring is also an integral feature of the crystallization substrates
examined in this study. Indeed, the incorporation of this ring system provides a basis for
enhanced halogen bond donor ability of the attached Nꢀhalophenyl groups via electron
withdrawing inductive effects. These same inductive effects, however, also impart greater
hydrogen bond donor ability upon the pyridinium C–H groups. In fact, pyridinium C–HꢁꢁꢁX−
hydrogen bonding is observed in each crystal structure. As discussed above, however, these
hydrogen bonding interactions are compatible with ArIꢁꢁꢁX− halogen bonding, but appear to
occur in preference to (or at the expense of) ArBrꢁꢁꢁCl− halogen bonding in many cases. This
may indicate that the Hꢀbond donor ability of these C–H groups is equal to or surpasses the XB
donor ability of the aryl bromines, but is less than the XB donor ability of the analogous
iodoarenes. NꢀHaloarylpyridinium ring systems possess significant polarity as well, and one
might imagine this feature could manifest itself through headꢀtoꢀtail type πꢀstacking interactions.
Significant πꢀπ contacts were only observed in half of the structures examined (1ꢀ2, 4, 6, and 9),
and so it appears this nonꢀcovalent interaction is of generally lesser importance than solid state
XB and Hꢀbonding.
CONCLUSIONS
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This study assessed the reliability of halogen bonding between Nꢀhaloarylpyridinium cations
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and halide anions in crystalline ion pair assemblies.
Five pairs of iodoꢀ and
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bromophenylpyridinium halides were prepared and structurally characterized. Examination of
the resulting crystal structures reveals the universal occurrence of ArIꢁꢁꢁX− (X = Cl or I) halogen
bonding. In contrast, ArBrꢁꢁꢁCl− halogen bonding interactions in analogous substrates are not as
frequent and are generally markedly weaker (according to distance criteria) than those
encountered in the iodoarene series. We speculate that the differences observed in the two series
of pyridinium salts are related to inherent differences in XB donor ability between the two
halogens such that activated bromoarene XB donors are unable to effectively compete with
hydrogen bond donors (water solvate molecules, aryl C–H groups) for the chloride anion
acceptors. Halogen bonding of halide anions to similarly activated iodoarene residues under the
same conditions, however, is not impeded. Examination of iodoarene substrates that possess XB
donor:halide ion acceptor ratios of 2:1 illustrate the ability to generate extended halogen bonded
networks and discrete halogen bonded dimers via Cl− bridging interactions. The generation of
these extended halogen bonding networks highlights the potential of diiodophenylpyridinium
cations to exert structureꢀdirecting effects over solid state selfꢀassembly processes. The
identification of recurring XB motifs in additional substituted (polyiodo)phenylpyridinium salts
is the subject of current studies.
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ASSOCIATED CONTENT
Supporting Information
Crystallographic data in CIF format, additional figures, PXRD data, and tables of selected
XB/HB distances and angles. This material is available free of charge via the Internet at
http://pubs.acs.org.
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