Halogen bonding and isostructurality in 2,4,6-Tris(2-halophenoxy)-1,3,5- triazines

Article abstract of DOI:10.1002/hc.20328

Crystal structures of 2,4,6-tris(2-halophenoxy)-1,3,5-triazines (halo =fluoro, chloro, bromo, iodo; 2-XPOT) are discussed in the background of 3-halophenoxy (3-XPOT) and 4-halophenoxy (4-XPOT) structures. Among interhalogen interactions, the electrostatic

Full text of DOI:10.1002/hc.20328

Heteroatom Chemistry
Volume 18, Number 2, 2007
Halogen Bonding and Isostructurality in
2,4,6-Tris(2-halophenoxy)-1,3,5-triazines
Binoy K. Saha and Ashwini Nangia
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Received 28 July 2006; revised 17 September 2006
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.20328
ABSTRACT: Crystal structures of 2,4,6-tris(2-
halophenoxy)-1,3,5-triazines (halo = fluoro, chloro,
bromo, iodo; 2-XPOT) are discussed in the
background of 3-halophenoxy (3-XPOT) and 4-
halophenoxy (4-XPOT) structures. Among inter-
halogen interactions, the electrostatic L-shaped type II
interactions are generally shorter than the inversion-
related type I geometry in 2-halo compounds. π-
Stacking of triazine rings at van der Waals separa-
INTRODUCTION
Halogens can make short contact with respect to
their van der Waals radius sum. Cl2, Br2, and I2
molecules participate in the side-on inter-halogen
interaction in their orthorhombic crystal structures
(Cmca) [1]. Sakurai et al. [2a] noted a directional
˚
tion (∼3.5 A) makes the well-known Piedfort Unit as-
sembly and the halogen atoms form a trimer motif.
2-FPOT and 2-ClPOT are 2D isostructural but there
are differences in the complete 3D molecular packing.
2-BrPOT and 2-IPOT are a 3D isostructural pair and
their isomorphous unit cells have a similarity index
of 0.008. The position of the halogen atom causes
structural differences in 2-, 3-, and 4-XPOT com-
pounds, with the para-series showing guest inclusion
and the ortho- and meta-compounds having single-
component close-packed structures. The Cambridge
Structural Database is analyzed for structural mimicry
upon halogen GRoup eXchange (GRX). Chloro-,
bromo-, and iodo-substituted compounds of the same
molecule (56 clusters) are isostructural in 30% cases,
Cl/Br are identical in 66% pairs, and Br/I in 50% ex-
•••
preference in the Cl Cl contact in the crystal struc-
ture of 2,5-dichloroaniline.∗ There is considerable
overlap between the spherical atoms but isotropic
atom–atom potential is inadequate to explain sev-
eral features showed by the halogen atoms. Bondi
[3] first observed that the effective shapes of some
atoms might not be truly spherical but rather ellip-
soid or pear-shaped, especially for the heavier el-
ements. Nyburg and Faerman [4] showed that the
atomic radii of nonspherical halogen atoms along
the C X bond vector are shorter than the distance
perpendicular to it. This so-called polar flattening in
organic chlorine (and heavier halogens) has led to
considerable speculation whether short directional
contacts are due to attractive forces or because of
a minimum in the repulsive potential. According
ꢀ
C
amples of the subdatabase.
2007 Wiley Periodicals,
Inc. Heteroatom Chem 18:185–194, 2007; Published on-
•••
to the prevailing model, halogen halogen contacts
∼
have two preferred geometries, type I (θ1 θ ) and
=
2
◦
◦
∼
∼
=
type II (θ1 180 and θ
90 ), as shown in Fig. 1.
=
2
Desiraju and Parthasarathy [5] emphasized specific
attractive forces between halogens on the basis of the
L-shaped geometry of X2 in the gas phase as well as
Correspondence to: Ashwini Nangia; e-mail: ashwini nangia@
rediffmail.com
Contract grant sponsor: Department of Science and
Technology, Government of India.
Contract grant number: SR/S5/OC-02/2002.
2007 Wiley Periodicals, Inc.
∗This structure was redetermined to high accuracy by Cox [2b].
c
ꢀ
185

186 Saha and Nangia
•••
results suggest that Cl Cl interactions are quite nor-
mal, with repulsion, dispersion, and electrostatic
contributions being the most important, but that
the nonsphericity of the chlorine charge distribu-
tion has a significant effect on these contributions
[6–8].
The heavy halogens are polarized positively in
the polar region (along the C X vector) and neg-
atively in the equatorial region (perpendicular to
the C X vector). The atomic size, radial anisotropy,
and polarization increase in the order Cl < Br < I
whereas electronegativity changes are in the re-
verse direction [9]. Thus, in the case of unsym-
FIGURE 1 Inter-halogen interactions: (a) Type I and (b) type
•••
•••
II geometry. Bent geometry in C I F C and C X Cl M
interactions (c and d) consistent with the electrostatic stabi-
lization shown in (b).
•••
metrical inter-halogen interactions, e.g. C F I C,
the negative equatorial part of the lighter halo-
gen preferentially approaches the positive polar re-
gion of the heavier halogen [10]. Anionic metal
halides also show a strong directionality to interact
with the polar region of the organic halogen [11].
Brammer and coworkers [12,13] showed that the
role of inorganic halide (M Cl) and organic halo-
gen (C X) are distinct and different in crystal pack-
statistical analysis of halogenated hydrocarbon crys-
•••
tal structures by considering the halogen halogen
contact area with respect to the total molecular area.
On the other hand, Price et al. [6] explained the
directionality to anisotropic electrostatic forces and
exchange repulsion without significant contribution
from charge transfer, discarding the possibility of
specific inter-chlorine contacts. Their computational
◦
•••
ing. The C X Cl angle is linear (150 170 ) whereas
◦
•••
the M Cl X angle is markedly bent (120–130 ) in
TABLE 1 Interaction Geometries in 2-XPOT Crystal Structuresa
˚
˚
Compound
2-FPOT
Interaction
d (A)
D(A)
θ( ◦)
•••
C(9) H N(3)
2.60
2.74
2.75
2.39
2.66
2.63
2.37
2.75
2.87
3.560(2)
3.527(3)
3.604(3)
3.310(4)
3.554(2)
3.701(2)
3.406(3)
3.767(2)
3.626(2)
3.773(0)
3.708(1)
3.459(1)
3.611(1)
3.596(8)
3.630(8)
3.542(8)
3.635(8)
3.729(1)
3.754(1)
3.514(4)
3.511(4)
3.522(5)
3.513(4)
3.721(4)
3.899(0)
3.823(0)
3.544(2)
147.7
129.6
135.0
141.9
140.0
169.9
159.8
155.9
127.2
•••
C(14) H N(1)
•••
C(17) H O(1)
•••
C(18) H F(1)
•••
2-ClPOT
C(10) H N(2)
•••
C(27) H N(3)
•••
C(32) H O(4)
•••
C(18) H O(3)
•••
C(19) H Cl(5)
•••
Cl(5) Cl(5)
150.8, 150.8 (I)
154.5, 106.5 (II)
160.5, 107.2 (II)
154.3, 105.9 (II)
150.1
•••
Cl(5) Cl(6)
•••
Cl(1) Cl(3)
•••
Cl(2) Cl(3)
•••
2-BrPOT
2-IPOT
C(15) H N(1)
2.62
2.65
2.59
2.64
•••
C(36) H N(6)
150.4
146.1
152.7
•••
C(8) H O(4)
•••
C(35) H O(2)
•••
Br(3) Br(5)
157.6, 91.9 (II)
147.3, 99.3 (II)
160.3
•••
Br(1) Br(5)
•••
C–Br(1) O(6)
•••
C(10) H N(5)
2.65
2.56
2.56
2.69
135.6
147.7
146.0
158.5
•••
C(10) H N(5)
•••
C(5) H O(3)
•••
C(35) H O(4)
•••
I(3) I(2)
147.4, 94.3 (II)
162.7, 87.5 (II)
160.1
•••
I(5) I(2)
•••
C–I(3) O(2)
aInter-halogen interactions are classified as type I or type II (Fig. 1). The type II geometry is generally shorter than the type I contact in the
same structure.
Heteroatom Chemistry DOI 10.1002/hc

Halogen Bonding and Isostructurality in 2,4,6-Tris(2-halophenoxy)-1,3,5-triazines 187
•••
C X Cl M interactions, consistent with the elec-
trostatic L geometry. Fluorine behaves quite dif-
ferently from the other three halogens because of
its hardness, small size, and high electronegativity.
Short inter-halogen contacts are a result of close
packing due to the elliptical shape of the halogen
thon [19,20]. Halogen bonding also plays an im-
portant role in biological recognition, for example,
in the binding of thyroxine to its receptor protein
[21].
•••
RESULTS AND DISCUSSION
Structural Analysis
atom and/or electrophile nucleophile pairing be-
cause of mutual polarization. Inter-halogen type I
inversion geometry is essentially a manifestation of
close packing, whereas directionality of the type II
interaction is due to charge polarization of the heavy
halogen [14].
We have previously described lattice inclusion struc-
tures of 2,4,6-tris(4-halophenoxy)-1,3,5-triazine host
for a wide variety of aromatic guests and archi-
tectural isomerism of the hexagonal framework
from infinite 1D channel (X = Cl) to a finite cav-
ity (X = I), depending on the X group. The chloro
Halogen bonding, a term used to describe bond-
ing between the electropositive portion of heavy
halogen atom and the negative electron cloud of
a heteroatom, is an n → σ∗ type interaction [15].
˚
host forms 12-A-diameter channels for guest in-
Its energy varies between 2 and 40 kcal/mol for
clusion whereas the larger iodo group results in a
cage cavity of the same dimension; both channel
and cage structures were observed in the bromo
derivative depending on the guest species [22–
27]. We discuss in this paper crystal structures
of 2,4,6-tris(2-halophenoxy)-1,3,5-triazine, which do
not have microporous cavities but instead organize
as close-packed structures. Similarly, 2,4,6-tris(3-
halophenoxy)-1,3,5-triazine also crystallize with-
out solvent inclusion [28,29]. These isomeric
−
•••
•••
I
the weakest Cl Cl contact to the strongest I2
donor–acceptor interaction [16]. Heteroditopic lig-
ands have been designed by Resnati and cowork-
ers [17,18] in multicomponent assemblies for di-
recting topochemical reactions. We recently showed
that the weak C I O2N halogen bond exerts a
structure-directing influence even in the presence of
strong hydrogen bonding groups, for example, the
•••
•••
urea α-network and the acid pyridine heterosyn-
TABLE 2 Crystallographic Data on 2-XPOT Compounds
2-FPOT
2-ClPOT
2-BrPOT
2-IPOT
Empirical formula
Formula weight
Crystal system
C21H12F3N3O3
411.34
C21H12Cl3N3O3
460.69
C21H12Br3N3O3
594.07
C21H12I3N3O3
735.04
Triclinic
Triclinic
Triclinic
Triclinic
Space group
T (K)
P1
298(2)
P1
100(2)
P1
298(2)
P1
100(2)
˚
a (A)
10.2873(14)
10.4290(14)
10.8937(15)
61.934(2)
70.098(2)
72.723(2)
1
10.5719(9)
10.8569(10)
20.0712(18)
99.9270(10)
90.8230(10)
115.8400(10)
2
12.6081(7)
12.9537(7)
15.6797(9)
72.3010(10)
69.5760(10)
67.1300(10)
2
12.6396(8)
13.1959(9)
15.7765(10)
71.4550(10)
68.9180(10)
66.9950(10)
2
˚
b (A)
˚
c (A)
α (◦)
β (◦)
γ (◦)
Zꢁ
Z
2
4
4
4
3
˚
Volume (A )
Dcalc (g/cm3)
F (000)
956.4(2)
1.428
420
2031.9(3)
1.506
936
0.480
2.07–25.50
−12 to 12
−12 to 13
−24 to 24
15603
2168.7(2)
1.819
1152
2211.2(2)
2.208
1368
µ (mm−1
)
0.117
5.608
4.268
θ
2.13–26.04
−12 to 12
−11 to 12
−13 to 13
6860
1.41–25.50
−15 to 15
−15 to 14
−18 to 18
16946
1.71–25.50
−15 to 15
−15 to 15
−19 to 19
25999
max.
Range h
Range k
Range l
N-total
N-independent
N-observed
R1 [I > 2σ(I )]
WR2
3602
2505
0.0429
0.1172
1.021
7512
6584
0.0327
0.0864
1.035
8064
4797
0.0489
0.1327
1.042
8229
7810
0.0217
0.0525
1.089
GOF
Heteroatom Chemistry DOI 10.1002/hc

188 Saha and Nangia
˚
compounds are abbreviated as 2-XPOT, 3-XPOT,
and 4-XPOT from our previous notation. The specific
molecular arrangements (shown in Figs. 2–4)
and intermolecular interactions (Table 1) in
these X-ray crystal structures (Table 2) are
analyzed.
triangular motif is 3.26 A, which is greater than the
˚
van der Waals sum (2.94 A) [33]. The stacking axis is
inclined to the PU axis along [1–2 2] by 26.6◦, unlike
in hexagonal packing, where it is perfectly parallel.
These tilted columns close-pack to generate the 3D
structure.
¯
¯
2-FPOT crystallizes in space group P1 and con-
2-ClPOT crystallizes in space group P1 with two
tains one molecule in the asymmetric unit. The Pied-
molecules in the asymmetric unit (Zꢁ = 2). The PU
dimers between symmetry-related molecules stack
similar to 2-FPOT in the tilted columns. These
parallel columns arrange in alternate layers of
symmetry-independent molecules. The π•••π stack-
ing distance between the triazine rings in PUs is 3.23
fort Unit dimer (PU) [30–32] is stabilized by π•••π
˚
•••
•••
stacking (3.34 A) and C H O and C H N interac-
tions from the ortho-phenyl donor to the phenoxy-
triazine group of the next layer. The ortho-halogen
on both sides prevents continuous stacks along the
PU axis, and so the molecules align with slight off-
set. One F atom from a PU sits on top of the in-
tramolecular fluoro trimer of the next PU dimer in
˚
and 3.44 A, such columns are tilted with respect to
the PU axis by 20.2◦ and 20.9◦, and the skew an-
◦
•••
gle between the columns is 56.7 . There are Cl Cl
˚
•••
the column (Fig. 2). The closest F F distance in the
interactions of 3.5–3.7 A, with a type II interaction
FIGURE 2 2D layers of PU dimers stacked with slight offset in the crystal structure of (a) 2-FPOT and (b) 2-ClPOT. One
halogen atom from a PU sits on top of the intramolecular halogen trimer of the next PU inthe column. (c) Type I and type II
•••
Cl Cl geometry in 2-ClPOT (see Table 1).
Heteroatom Chemistry DOI 10.1002/hc

Halogen Bonding and Isostructurality in 2,4,6-Tris(2-halophenoxy)-1,3,5-triazines 189
FIGURE 3 (a) Bifurcated inter-halogen interaction of type II geometry in the crystal structure of 2-BrPOT and (b) Piedfort Unit
to show the pseudo-hexagonal arrangement. The crystal structure of 2-IPOT is identical.
•••
being the shortest (Table 1). The 2D arrangement in
2-ClPOT is isostructural to 2-FPOT, that is, their
layer motifs are identical but there are differences
in the 3D molecular arrangement. We have dis-
cussed 1D, 2D, and 3D isostructurality in steroid
and polycarboxylic acid crystal structures [34–36],
and Ka´lma´n et al. have analyzed polymorphic crys-
tal structures at increasing degrees of similarity [37].
2-BrPOT crystallizes with two molecules in the
to each other. The geometry of the type II I I
◦
◦
˚
˚
interaction is 3.90 A, 147.4 , 94.3 and 3.82 A,
◦
◦
•••
162.7 , 87.5 together with electrostatic C I O and
C I π interactions in the structure. As the type
II interaction approaches the optimal L-geometry,
the inter-halogen Br Br and I I distances become
shorter.
The crystal structures of 3-XPOT compounds
were reported previously [28,29]. 3-ClPOT, 3-BrPOT,
and 3-MePOT are isostructural in space groupP3c1.
•••
•••
•••
¯
¯
asymmetric unit in space group P1. Here also sim-
ilar PUs are observed between symmetry-related
molecules and the distance between the triazine
This indicates that the halogen group is play-
ing more of a space-filling role. Similar to the
packing in guest-free 4-BrPOT [39], these struc-
tures have continuous PUs of hexagonal symme-
try (Fig. 4). The crystal structure of 3-IPOT (space
˚
planes is 3.46 and 3.62 A. Symmetry-independent
PUs are aligned almost perpendicular (87.2◦) be-
•••
cause the bromo groups form type II Br Br contact
◦
◦
◦
◦
˚
˚
¯
of 3.73 A, 157.6 , 91.9 and 3.75 A, 147.3 , 99.3
group R3) has 1/3 molecule in the asymmetric
•••
•••
(Fig. 3) along with C Br O and C Br π inter-
actions. 2-IPOT is isostructural to 2-BrPOT and
their unit-cell similarity index, ꢀ = 0.008 [38].∗ The
unit. The molecules are stacked in the C3i-PU as
•••
a helix along the c-axis via type II I I interac-
◦
◦
˚
tion (3.85 A, 169.9 , 83.0 ) because of mutual po-
larization between the soft iodine atoms. Triazine
˚
triazine planes are 3.34 and 3.49 A apart in the
symmetry-independent PUs that are inclined at 87.1◦
rings are separated by 3.42 and 3.87 A in the PU
and connected via C H O and C H N interac-
˚
•••
•••
tions via the ortho-H donors whereas the meta-H
atoms participate in C H I interaction. In con-
∗The init cell similarity index ꢀ = | (a + b + c) ÷ (aꢁ + bꢁ + cꢁ) |
•••
−1, where a, b, c and aꢁ, bꢁ, cꢁ are the orthogonalized lattice pa-
trast to differences in 3-XPOT structures, 4-XPOT
structures have hexagonal cavities or channels for
guest inclusion (X Cl, Br, I). A slice of the hexag-
onal layer mediated via the iodo trimer synthon in
4-IPOT host is shown in Fig. 4 [27].
∼
rameters (Lo¨wdin program) of the isomorphous crystals. ꢀ
0
=
indicates identity between crystal structures. If two crystal struc-
tures are very different, then ꢀ is not calculated for such pairs. We
thank Prof. A. Ka´lma´n and Dr. L. Fa´bia´n (Hungarian Academy of
Sciences) for a copy of the program to calculate isostructurality
indices.
Heteroatom Chemistry DOI 10.1002/hc

190 Saha and Nangia
•••
FIGURE 4 (a) Stacked PU column in 3-ClPOT. There are no specific Cl Cl interactions. 3-BrPOT and 3-MePOT areisostruc-
˚
•••
tural. (b) I I helix and PU column in the structure of 3-IPOT. (c) Hexachlorobenzene guest inclusion in the 12 A on each side
hexagonal cavity of the 4-IPOT host. The cage structure of 4-IPOT has C3i -PU, but π–π stacking is absent in the channel
structures of 4-ClPOT and 4-BrPOT. The 2D hexagonal layer is identical in these 4-XPOTs.
A search of the Cambridge Structural Database
(CSD version 5.26, February 2005 update) was car-
ried out to determine the frequency of isostruc-
turality in organic halogen compounds (i.e., those
containing a Cl, Br or I group) and the proba-
bility that the bromo derivative is similar to the
chloro or iodo crystal structure was estimated. A
subdatabase of crystal structures for which all three
halogen derivatives of the same organic compound
are reported was prepared manually. Monovalent
iodine-containing organic compounds whose 3D
coordinate are determined, are single-component,
not disordered, and not polymeric; no errors, no
ions, no powder structures, and R <0.10 were
Isostructurality in Halogen Compounds
Motherwell and coworkers [40] developed a program
GRX (GRoup eXchange) to search crystal structures
related by functional group replacement. They an-
alyzed methyl–chlorine and methyl–bromine sub-
stitution change in crystal structures. The simu-
lated powder patterns are then compared to check
isostructurality in crystal structure pairs. There is
isostructural exchange of chlorine or bromine for
the methyl group in 26% and 25% cases, indicating
that both these halogens are equally effective in re-
placing a methyl group without changing the crystal
packing [40].
Heteroatom Chemistry DOI 10.1002/hc

Halogen Bonding and Isostructurality in 2,4,6-Tris(2-halophenoxy)-1,3,5-triazines 191
TABLE 3 CSD Refcodes of the Same Molecule Having Cl, Br, and I Derivativesa
No.
Fluoro
HUFVEJ
BEFSOV
Chloro
Bromo
Iodo
ꢀ
1
2
3
ACOKAE
BAXTUQ
SUHSET
ACOKEI
BAXVAY
JUKVIU
ACOKIM
BAXVIG
BEFSUB
I/Br = 0.029
I/Cl = 0.008
I/Br = 0.023
Br/F = 0.068
I/F = 0.093
I/Br = 0.074
Br/F = 0.026
I/F = 0.103
Nil
4
PFBZAD01
CLBZAP01
BRBZAP
BENMOW01
5
6
7
8
9
UGIGEW
TECLPH01
CCBCBT
SEGWUW
DCLMET10
NABRAJ
BROPOS
TBPHAN
CBBCBT
SEGXAD
DBRMET10
BRBZAM
BENXAT
BOPDOZ
CIBCBT
DIHRIV
DIMETH01
DUMNUU
Br/Cl = 0.020
I/Br = 0.032
Br/Cl = 0.005
I/Br = 0.058
I/Br = 0.017
Br/Cl = 0.010
I/Cl = 0.027
Br/Cl = 0.026
Br/Cl = 0.0003
I/Br = 0.037
Br/Cl = 0.015
I/Br = 0.035
Br/Cl = 0.032
I/Cl = 0.068
I/Cl = 0.032
I/Br = 0.017
I/Br = 0.057
Br/Cl = 0.029
I/Cl = 0.087
Br/Cl = 0.007
I/Br = 0.018
Br/Cl = 0.022
I/Br = 0.025
Br/Cl = 0.003
I/Cl = 0.022
Nil
Br/Cl = 0.019
Br/Cl = 0.009
Br/Cl = 0.001
Br/Cl = 0.009
Br/Cl = 0.003
Br/Cl = 0.004
Nil
I/Br = 0.023
Br/Cl = 0.031
I/Cl = 0.055
I/Br = 0.019
Cl/F = 0.046
I/Br = 0.021
Br/Cl = 0.009
I/Cl = 0.030
VAXLUB
10
BENAFM10
11
12
13
CLANIC05
BENCLN02
FABDIW
PBRANL01
BENBRN02
FABDOC
EJAYET
ENIGIR
FABDUI
KIFXIG
14
GOGXOP
GOGXEF
PALWOO
GIHTIA
15
16
17
HIRNEB
BIGSUF
TIYJEQ01
CLBZAM10
CCACEN
TIYJIU01
BRBZAO
BCACEN
HIRPAZ01
IBNZAM
ICACEN
18
19
FDOURD
DFPSLO
CLDOUR
CLPSUL01
BROXUR10
BPHSUL01
IDOXUR
IPSULO
20
CPPTLM01
BPPHIM
IPTHIM10
21
22
23
24
25
26
27
28
29
CUNWIR
CLURAC10
CLURID10
JENHIV
UNASOR
BRURAC10
BRURID10
JIKCAH
SINVIU10
MUTZIK
MUTZUW
LIKJEU
VIXHAL01
IQITIL
FURACL
TAPSEI
IURACL10
IURIDN10
KEYNUX
KICRET
LALMEQ
LALNUH
LIZNEN
LUSNUI
SINVOA
MUTZOQ
MUVBAG
LIKHUI
LIKHOC
LUSNAO
30
31
NACBUO
NACCEZ
NEGJAK
NACCAV
NEGKIT
NACBOI
NEGLEQ
32
33
NEGJEO
NOTZAX
NEGKOZ
NOTZEB
NEGLIU
NOTZIF
Br/Cl = 0.005
I/Br = 0.009
Br/Cl = 0.005
I/Cl = 0.009
I/Br = 0.009
Br/Cl = 0.005
I/Cl = 0.014
I/Br = 0.021
Br/Cl = 0.007
I/Cl = 0.028
34
35
WIKKUW
IHARAK
WERBAW
QUDHEC
NUZNOL
OCOQIG
Continued
Heteroatom Chemistry DOI 10.1002/hc

192 Saha and Nangia
TABLE 3 Continued
No.
Fluoro
Chloro
Bromo
Iodo
ꢀ
36
37
38
ODAHOQ
CLBZAC
DCLBIP
QODQUV01
BRBZAC
HIQQON
ODAHUW
OIBZAC
PIPROV
Br/Cl = 0.003
Br/Cl = 0.006
I/Br = 0.021
Cl/F = 0.046
Br/Cl = 0.003
I/Br = 0.005
Br/Cl = 0.008
Br/Cl = 0.017
Br/Cl = 0.001
Cl/F = 0.058
I/Br = 0.052
Br/Cl = 0.020
I/Cl = 0.074
I/Br = 0.0003
Br/Cl = 0.001
I/Br = 0.009
Br/Cl = 0.003
I/Cl = 0.012
I/Br = 0.012
Br/Cl = 0.006
I/Cl = 0.018
Nil
Br/Cl = 0.001
Br/Cl = 0.019
I/Br = 0.007
Br/Cl = 0.013
I/Cl = 0.006
I/Br = 0.015
Br/Cl = 0.006
I/Cl = 0.021
Nil
FBENZA
PUGPIQ
39
40
ZIVLIZ
CHLSAN
QOMYIA
BSALAN
QOMYOG
RAVTIR
41
42
YICFAR
CLANAC10
YICFEV
VAGTUS
RIWTOG
SANZUC
FLUANA
HEVLAV
43
ZEPDAZ
PUZHIB
SAQZOY
44
45
46
DCLANT01
ZZZVTY12
VOYMUR
DBANTH01
TPHMBR01
VOYNAY
TECWUT
TEWWEX
VOYNEC
47
VICXOU
VUCHAC
VUCHEG
48
49
50
51
WOJXUO
CLNIBZ
XALBER
XAXQIW
WOJXIC
BRNIBZ
MALGOV
XAXQOC
WOJXOI
WURTOS
XALBIV
XAXQUI
52
YIHQAH
YIHQUB
YIJQAJ
53
54
CARBTC
CBENPH
CTBROM
CUZKUD
ZZZKDW01
ZZZOVY01
HATXIJ
Cl/F = 0.028
I/Br = 0.043
I/Br = 0.009
I/Br = 0.028
55
56
EBICUO
EBIDAV
EYISIO
EBIDEZ
BRACPH02
EBIDID
EYITAH01
aIn some cases the F derivative is also reported. Unit cell similarity index, ꢀ [38], is calculated for isostructural pairs.
retrieved. Each structure in the iodo subdatabase
(the smallest category among three halogens) was
then searched for the corresponding bromo and
chloro derivative. If the corresponding fluoro com-
pound is known then this entry was added to Table 3.
The unit cell similarity index, ꢀ [38], was calculated
for pairs of crystal structures.
There are 56 crystal structures wherein chloro,
bromo, and iodo derivative of the same compound is
reported and out of these the fluoro structure is also
known in 21 cases. There is no example wherein all
halogen derivatives (F, Cl, Br, I) of the same com-
pound are isostructural. Interestingly, the chloro,
bromo, and iodo compounds are isostructural in
17 cases out of 56, which is a large percentage
(30%) for organic compounds. In this series, the
more polarizable Br and I derivatives display
similar packing in 28 pairs (50%). Interestingly,
the Br and Cl substituents show the most fre-
quent isostructurality in 37 examples (66%). There
are only four examples where chloro and fluoro
compounds are isostructural, for example, methyl
4-halo-1-cubanecarboxylate,
2,2ꢁ-dihalobiphenyl,
haloanilic acid, and 4,4ꢁ-dihalobenzophenone (en-
tries 30, 38, 42, and 54, respectively). There are three
entries (30, 38, and 54) where Cl is isostructural
to F and I is isostructural to the Br analog. A
new finding from our search is that there are at
least three examples, (+)-(3R,3aR,6R,7S,7aS,8S)-
6-halo-2,3,3a,6,7,7a-hexahydro-8-methyl-2-oxo-3,6-
methano-1-benzofuran-7-yl crotonate, (4-halophenyl)-
propiolic acid, and 4-halobenzoic acid (entries
2, 3, and 4), wherein the terminal members are
isostructural but not the middle ones. For example,
the bromo derivative of the crotonate is different
from the isostructural chloro and iodo pair, and the
Heteroatom Chemistry DOI 10.1002/hc

Halogen Bonding and Isostructurality in 2,4,6-Tris(2-halophenoxy)-1,3,5-triazines 193
chloro analog of the propiolic acid and benzoic acid
EXPERIMENTAL
Synthesis
structure is different from the other three isostruc-
tural members in each case. This last observation is
surprising because Kitaigorodskii generalized that
“if the end members of a series are isomorphous,
the middle ones are always so as well” [41]. These
structures should be examined further to check
for polymorphism or is it just a few outliers in a
statistical distribution? The reader is referred to the
CSD [40] for a detailed examination of all crystal
structures listed in Table 3.
Four millimoles of 2-halophenol and 4 mmol of
KOH were dissolved in THF (30 mL) and stirred for
30 min at room temperature. The reaction mixture
was cooled to 0◦C and then slowly 1 mmol of cya-
nuric chloride was added and stirred for 1 h at 0◦C.
After continuing for 48 h at room temperature, the
reaction mixture was poured into crushed ice. The
thick white precipitate (75% yield) was filtered by
vacuum suction and washed with methanol, dried
and purified by column chromatography. All com-
pounds showed satisfactory NMR spectra.
CONCLUSIONS
Isostructurality is important not only in crystal en-
gineering but also in the related areas of drug de-
sign [36], materials science [42], and the holy grail
of crystal structure prediction [43]. The question of
“whether a particular functional group or position
change on a molecule will lead to a similar or dif-
ferent crystal structure” has no definite answer at
the present time. One can make an educated guess
from the known structural data to forecast how new
members in a given series will crystallize but there is
no rigorous predictive model to relate the molecular
structure diagram to the crystal structure packing.
We observe in the X-POT family of structures that
there are differences depending on the ortho, meta,
para-position of the halogen group. In the 4-XPOT
series, Cl, Br and I are isostructural at the 2D honey-
comb network level but the 3D molecular arrange-
ment is different for chloro and iodo whereas bromo
behaves like one of these depending on the guest
species. In the 2-XPOT series, F and Cl are identical
only at the 2D layer similarity, and the crystal struc-
tures of the Br and I compounds are 3D isostruc-
tural. We became aware of the crystal structures of
2-XPOT compounds determined at different temper-
atures [44] compared to those carried out by us and
their structural similarity (morphotropism) [45,46]
after the submission of our work. 3-IPOT is differ-
ent from its lower halogen analogs because of the
1
2-FPOT: H NMR (CDCl3, 400 MHz) δ: 7.09 (m,
6H), 7.17 (m, 6H).
1
2-ClPOT: H NMR (CDCl3, 400 MHz) δ: 7.39 (d,
J = 8 Hz, 3H), 7.26 (m, 6H), 7.17 (d, J = 8 Hz, 3H),
7.17 (t, J = 8 Hz, 3H).
1
2-BrPOT: H NMR (CDCl3, 400 MHz) δ: 7.56 (d,
J = 8 Hz, 3H), 7.29 (t, J = 8 Hz, 3H), 7.17 (d, J = 8
Hz, 3H), 7.10 (t, J = 8 Hz, 3H).
1
2-IPOT: H NMR (CDCl3, 400 MHz) δ: 7.78 (d,
J = 8 Hz, 3H), 7.32 (t, J = 8 Hz, 3H), 7.13 (d, J = 8
Hz, 3H), 6.96 (t, J = 8 Hz, 3H).
Crystallization
A solution of the appropriate 2-XPOT compound
(200 mg) in 10 mL chloroform afforded diffraction-
quality single crystals by slow evaporation of the sol-
vent over 1 week.
X-ray Crystallography
Reflections were collected for single crystals of 2-
FPOT, 2-ClPOT, 2-BrPOT, and 2-IPOT on a Bruker
SMART APEX CCD area detector system at 298,
100, 298, and 100 K, respectively (Mo Kα radia-
•••
I I helix. The electrostatic type II inter-halogen in-
˚
teraction is generally shorter than the space-filling
type I geometry. The CSD trends on halogen ex-
change indicate that the Br atom resides in between
Cl and I atoms not only in the periodic table but
also in terms of its supramolecular behavior based
on its frequency for isostructural exchange. We can
only speculate that Zꢁ = 1 for 2-FPOT but Zꢁ = 2 for
2-ClPOT, 2-BrPOT, and 2-IPOT because of spe-
cific but weak inter-halogen interactions in the lat-
ter structures, analogous to recent observations on
tion, λ = 0.71073 A). Multiscan absorption correc-
tion was applied for 2-XPOT data in SADABS. Struc-
ture solution and refinement were performed us-
ing SHELXS-97 and SHELXL-97 [50]. Hydrogen
atoms were generated at idealized geometries and
isotropically refined using the Riding model. Refine-
ment of coordinates and anisotropic thermal param-
eters of non-hydrogen atoms was carried out by the
full-matrix least-squares refinement method. Crys-
tallographic .cif files (CCDC Nos. 624302–624305)
are freely available from www.ccdc.cam.ac.uk or de-
posit@ccdc.cam.ac.uk.
•••
C H O interactions and multiple molecules in the
asymmetric unit [47–49].
Heteroatom Chemistry DOI 10.1002/hc

194 Saha and Nangia
[23] Jetti, R. K. R.; Thallapally, P. K.; Xue, F.; Mak,
T. C. W.; Nangia, A. Tetrahedron 2000, 56, 6707–
6719.
[24] Jetti, R. K. R.; Nangia, A.; Xue, F.; Mak, T. C. W.
Chem Commun 2001, 919–920.
[25] Broder, C. K.; Howard, J. A. K. H.; Keen, D. A.;
Wilson, C. C.; Allen, F. H.; Jetti, R. K. R.; Nangia,
A.; Desiraju, G. R. Acta Crystallogr 2000, B56, 1080–
1084.
[26] Jetti, R. K. R.; Thallapally, P. K.; Nangia, A.; Lam,
C.-K.; Mak, T. C. W. Chem Commun 2002, 952–953.
[27] Saha, B. K.; Jetti, R. K. R.; Reddy, L. S.; Aitipamula,
S.; Nangia, A. Cryst Growth Des 2005, 5, 887–899.
[28] Thalladi, V. R.; Brasselet, S.; Weiss, H.-C.; Blaser, D.;
Katz, A. K.; Carrell, H. L.; Boese, R.; Zyss, J.; Nangia,
A.; Desiraju, G. R. J Am Chem Soc 1998, 120, 2563–
2577.
ACKNOWLEDGMENTS
We thank the Intensification of Research in High Pri-
ority Areas (IRPHA) for the X-ray CCD diffractome-
ter. The University with Potential for Excellence
(UPE) program provides the infrastructure support
at the University of Hyderabad. B.K.S. thanks the
Council of Scientific and Industrial Research (CSIR)
for fellowship. We thank the referees for their valu-
able suggestions and especially one of them for
bringing references 44–46 to our attention.
REFERENCES
[29] Saha, B. K.; Aitipamula, S.; Banerjee, R.; Nangia, A.;
Jetti, R. K. R.; Boese, R.; Lam, C.-K.; Mak, T. C. Mol
Cryst Liq Cryst 2005, 440, 295–316.
[30] Jessiman, A. S.; MacNicol, D. D.; Malinson, P. R.;
Vallance, I. J Chem Soc Chem Commun 1990, 1619–
1621.
[1] Desiraju, G. R. Crystal Engineering: The Design of
Organic Solids; Elsevier: Amsterdam, 1989; Ch. 6.
[2] (a) Sakurai, T.; Sundaralingam, M.; Jeffrey, G. A. Acta
Crystallogr 1963, 16, 354–363; (b) Cox, P. J. Acta Crys-
tallogr 2001, E57, o1203–o1205.
[31] Fa´bia´n, L.; Bombicz, P.; Czugler, M.; Ka´lma´n, A.;
Weber, E.; Hecker, M. Supramol Chem 1999, 11, 151–
167.
[3] Bondi, A. J Phys Chem 1964, 68, 441–451.
[4] Nyburg, S. C.; Faerman, C. H. Acta Crystallogr 1987,
B43, 106–110.
[32] Czugler, M.; Weber, E.; Pa´rka´nyi, L.; Korkas, P. P.;
Bombicz, P. Chem Eur J 2003, 9, 3741–3747.
[33] Choudhury, A. R.; Guru Row, T. N. Cryst Growth Des
2003, 4, 47–52.
[34] Anthony, A.; Jasko´lski, M.; Nangia, A.; Desiraju, G. R.
Chem Commun 1998, 2537–2538.
[5] Desiraju, G. R.; Parthasarathy, R. J Am Chem Soc
1989, 111, 8725–8726.
[6] Price, S. L.; Stone, A. J.; Lucas, J.; Rowland, R. S.;
Thornley, A. E. J Am Chem Soc 1994, 116, 4910–4918.
[7] Mitchell, J. B. O.; Price, S. L. J Phys Chem A 2001,
105, 9961–9971.
[35] Anthony, A.; Jasko´lski, M.; Nangia, A. Acta Crystal-
logr 2000, B56, 512–525.
[8] Day, G. M.; Price, S. L. J Am Chem Soc 2003, 125,
16434–16443.
[36] Babu, N. J.; Nangia, A. Cryst Growth Des 2006, 6,
1753–1756.
[37] Fa´bia´n, L.; Ka´lma´n, A. Acta Crystallogr 2004, B60,
547–558.
[9] Pogliani, L. New J Chem 2003, 27, 919–927.
[10] 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.
[38] Fa´bia´n, L.; Ka´lma´n, A. Acta Crystallogr 1999, B55,
1099–1108.
[11] Freytag, M.; Jones, P. G.; Ahrens, B.; Fischer, A. K.
New J Chem 1999, 23, 1137–1139.
[39] Reichenba¨cher, K.; Su¨ss, H. I.; Stoeckli-Evans, H.;
Bracco, S.; Sozzani, P.; Weber, E.; Hulliger, J. New J
Chem 2004, 28, 393–397.
[40] Chisholm, J.; Pidcock, E.; van de Streek, J.; Infantes,
L.; Motherwell, S.; Allen, F. H. Cryst Eng Commun
2006, 8, 11–28.
[41] Kitaigorodskii, A. I. Organic Chemical Crystallogra-
phy; Consultants Bureau: New York, 1961; Ch. 4.
[42] Saha, B. K.; Nangia, A.; Nicoud, J.-F. Cryst Growth
Des 2006, 6, 1278–1281.
[43] Hundt, R.; Scho¨n, J. C.; Jansen, M. J. Appl Crystallogr
2006, 39, 6–16.
[12] Zordan, F.; Brammer, L.; Sherwood, P. J Am Chem
Soc 2005, 127, 5979–5989.
[13] Espallargas, G. M.; Brammer, L.; Sherwood, P.
Angew Chem Int Ed 2006, 45, 435–440.
[14] Reddy, C. M.; Kirchner, M. T.; Gundakaram, R. C.;
Padmanavan, K. A.; Desiraju, G. R. Chem Eur J 2006,
12, 2222–2234.
[15] Prout, C. K.; Kamenar, B. Molecular Complexes; Elek
Science: London, 1973; Vol. 1.
[16] Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G.
Acc Chem Res 2005, 38, 386–395.
[17] Caronna, T.; Liantonio, R.; Logothetis, T. A.; Metran-
golo, P.; Pilati, T.; Resnati, G. J Am Chem Soc 2004,
126, 4500–4501.
[44] Ba´thori, N.; Biha´tsi, L.; Czugler, M.; Bombicz, P. Acta
Crystallogr 2005, A61, C282–C283.
[45] Ka´lma´n, A. Acta Crystallogr 2005, A61, C284.
[46] Ka´lma´n, A. Acta Crystallogr 2005, B61, 536–547.
[47] Roy, S.; Banerjee, R.; Nangia, A.; Kruger, G. J. Chem
Eur J 2006, 12, 3777–3788.
[48] Nichol, G. S.; Clegg, W. Cryst Growth Des 2006, 6,
451–460.
[49] Chandran, S. K.; Nangia, A. Cryst Eng Commun 2006,
8, 581–586.
[50] SHELXS-97, SHELXL-97: Sheldrick, G. M. Program
for the Solution and Refinement of Crystal Struc-
tures, University of Go¨ttingen, Germany, 1997.
[18] Corradi, E.; Meille, S. V.; Messina, M. T.; Metrangolo,
P.; Resnati, G. Angew Chem Int Ed 2000, 39, 1782–
1786.
[19] George, S.; Nangia, A.; Lam, C.-K.; Mak, T. C. W.;
Nicoud, J.-F. Chem Commun 2004, 1202–1203.
[20] Saha, B. K.; Nangia, A.; Jasko´lski, M. Cryst Eng Com-
mun 2005, 7, 355–358.
[21] Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Proc
Natl Acad Sci USA 2004, 101, 16789–16794.
[22] Jetti, R. K. R.; Xue, F.; Mak, T. C. W.; Nangia, A. Cryst
Eng 1999, 2, 215–224.
Heteroatom Chemistry DOI 10.1002/hc