Concomitant formation of two different solvates of a hexa-host from a binary mixture of solvents

Article abstract of DOI:10.1039/b813891e

Crystallization of hexakis(4-cyanophenyloxy)benzene from a mixture of two different solvents produces two different solvates concomitantly, which were characterized by X-ray diffraction, thermal analysis and NMR spectroscopy. The Royal Society of Chemistry.

Full text of DOI:10.1039/b813891e

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Concomitant formation of two different solvates of a hexa-host
from a binary mixture of solventsw
Dinabandhu Das and Leonard J. Barbour*
Received (in Cambridge, UK) 11th August 2008, Accepted 10th September 2008
First published as an Advance Article on the web 26th September 2008
DOI: 10.1039/b813891e
Crystallization of hexakis(4-cyanophenyloxy)benzene from a
mixture of two different solvents produces two different solvates
concomitantly, which were characterized by X-ray diffraction,
thermal analysis and NMR spectroscopy.
solvents.13 Apart from this passing reference to the concomi-
tant occurrence of mixed crystals of solvates, there is, to the
best of our knowledge, no other report of this phenomenon.
Here we report the rare case of concomitant formation of two
different solvates (i.e. (ii) + (iii), or (v) in Scheme 1b) of a
hexa-host 1 (Scheme 2) from the mixture of methanol (MeOH)
and acetonitrile (ACN).
Many organic molecules have the intrinsic ability to occlude
guest molecules upon crystallization.1 When the guest mole-
cules are derived from the solvent of crystallization, the
resulting inclusion compounds are broadly termed
‘‘solvates’’.2 Solvates have recently attracted much attention
(especially from the pharmaceutical industry) because inclu-
sion of solvent in the crystal lattice can influence properties
such as the solubility and dissolution rate of a drug substance.3
In materials science, solvent inclusion can also affect various
properties such as magnetism,4 ferroelectricity,5 chemical
storage,6 second harmonic generation7 and catalysis.8 Further-
more, selective inclusion of solvent is useful in separation
processes.9
When a host (H) is crystallized from a solvent (S), either
only one kind of solvate (HꢀnS) could be formed, or different
solvates such as Hꢀn1S, Hꢀn2S, etc. can result, depending on
the stoichiometry of H and S (Scheme 1a). The solvates of the
latter case have been called ‘‘concomitant pseudopoly-
morphs’’10 (we note that the term ‘‘pseudopolymorph’’ in
the context of solvates has recently been the subject of some
controversy11). In principle, there are four possible structural
outcomes of crystallizing H from a binary mixture of solvents
S1 and S2: (i) the host can crystallize in its apohost form (i.e.
without solvent); (ii) H can include only solvent S1 to form
Hꢀn1S1; (iii) H can include only solvent S2 to form Hꢀn2S2 and
(iv) both solvents can be included to yield a so-called ‘‘mixed
solvate’’12 Hꢀn1S1ꢀn2S2. Concomitant combinations of (ii) to
(iv) yield a further four mixed crystal possibilities (Scheme 1b).
While possibilities (ii) to (iv) often occur when an organic host
is crystallized from a mixture of solvents,12 mixed crystal
solvates are generally not observed. In a recent report by
Nassimbeni et al., it was shown that the solvates obtained by
crystallization of a particular host from a binary mixture of
solvents depend on the nature and relative proportions of the
Scheme 1 Different possibilities of solvate formation.
Compound 1 was prepared and purified according to a
previously reported procedure14 and dissolved in an equal-
volume mixture of MeOH and ACN, which was allowed to
evaporate slowly at room temperature. After four days, crys-
tals with two different morphologies were observed (Fig. 1).
The plate-shaped and needle-shaped crystals were separated
manually and both were characterized by X-ray diffraction,
thermal analysis and NMR spectroscopy. Single crystal X-ray
diffraction (SCD)z reveals that the plate-shaped crystals are
1ꢀMeOH and that the needle-shaped crystals are 1ꢀACN
(Fig. 2). The MeOH solvate crystallizes in the space group
ꢀ
P1 with one host and one MeOH molecule in the asymmetric
unit. The MeOH molecule interacts with 1 by means of
O–Hꢀ ꢀ ꢀN and C–Hꢀ ꢀ ꢀO hydrogen bonds (see ESIw). The
ACN solvate crystallizes in the space group Pbca with Z =
8 and its asymmetric unit also consists of one host and one
Department of Chemistry, University of Stellenbosch Private bag XI,
Stellenbosch, South Africa. E-mail: ljb@sun.ac.za;
Fax: +27-808-21-3335; Tel: +27-808-21-3335
w Electronic supplementary information (ESI) available: Synthesis,
experimental details, packing diagram, NMR spectra, table for hydro-
gen bonding geometry. CCDC reference numbers 698337–698338. For
ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/b813891e
Scheme 2 Hexakis(4-cyanophenyloxy)benzene (1).
ꢁc
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Fig. 1 Photomicrograph of concomitant solvates of 1.
Fig. 3 TGA and DSC thermograms of (a) 1ꢀMeOH and (b) 1ꢀACN.
Fig. 2 The asymmetric units of (a) 1ꢀMeOH and (b) 1ꢀACN. Atoms
are shown with 70% probability thermal ellipsoids.
guest molecule. The ACN molecules are stabilized by the
formation of C–Hꢀ ꢀ ꢀN hydrogen bonds with 1. Packing analy-
sis of 1ꢀACN shows that the ACN molecules are also interacting
with one another via pꢀ ꢀ ꢀp contacts to form solvent dimers.
Interestingly, 1 assumes the aaabab conformation in each
solvate, which is very unusual for hexa-host molecules.15,16
Thermal analysis of both the solvates was carried out and
the results are shown in Fig. 3. The TGA traces of both
solvates indicate that solvent loss occurs as a single-step
process in each case. The DSC thermogram of 1ꢀMeOH
(Fig. 3a) exhibits a small endotherm at Ton = 120 1C (Ton is
the onset temperature), representing loss of methanol, fol-
lowed by melting of 1 at Ton = 270 1C. Similarly, the DSC
thermogram of 1ꢀACN (Fig. 3b) shows an endotherm at Ton
= 171 1C associated with the loss of acetonitrile, followed by
melting at Ton = 270 1C. The parameter Ton ꢂ Tb can be used
as a reliable measure of the thermal stability of the solvates
Fig. 4 Overlay of experimental (red) and simulated (black) XRPD
patterns of (a) 1ꢀMeOH and (b) 1ꢀACN. (c) Experimental XRPD
patterns of desolvated 1ꢀMeOH (black) and 1ꢀACN (red).
ꢁc
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where Tb is the boiling point of the solvent.17 For 1ꢀMeOH
Ton ꢂ Tb = 56 1C and for 1ꢀACN it is 89 1C. These parameters
suggest that the acetonitrile solvate is more thermally stable
than the methanol solvate, although the latter contains stron-
ger hydrogen bonds between host and guest.
1991, ch. 5; (b) Comprehensive Supramolecular Chemistry: Solid-
state Supramolecular Chemistry: Crystal Engineering, ed. D. D.
MacNicol, F. Toda and R. Bishop, Pergamon Press, Oxford,
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The manually separated crystals were ground mildly using a
mortar and pestle and the powdered samples were analyzed by
X-ray powder diffraction (XRPD) in order to reveal the bulk
phase identities of the plate- and needle-shaped crystals. The
experimental XRPD patterns were compared with the simu-
lated patterns from the SCD structures. Fig. 4 shows excellent
agreement between experimental and simulated patterns for the
two solvates. The 1ꢀMeOH and 1ꢀACN solvates were also
prepared separately by dissolving 1 in the corresponding solvent
in each case. The XRPD patterns of the separately prepared
solvates are similar to those of the concomitant solvates.
Desolvation of both solvates by heating at 200 1C yields the
same crystalline phase of 1 as confirmed by XRPD (Fig. 4c).
The separated concomitant solvates were analyzed by NMR
spectroscopy for further confirmation of different solvent inclu-
sion by 1. 13C NMR spectra show the characteristic peaks of the
methyl carbon atoms of methanol and acetonitrile at 49.3 ppm
and 1.87 ppm, respectively (see ESIw). The cyano carbon atom of
acetonitrile is confirmed by a peak at 118.7 ppm. The NMR
results strongly suggest that the crystals of the two different
morphologies include methanol and acetonitrile separately.
In summary, we have highlighted the rare occurrence of the
formation of two different solvates concomitantly from a
binary mixture of solvents. We have demonstrated this phe-
nomenon using a hexa-host system crystallized from a mixture
of methanol and acetonitrile, and our results are supported
unequivocally by single-crystal X-ray diffraction, powder
X-ray diffraction, thermal analysis and NMR spectroscopy.
We are grateful to the SARChI Programme of the Depart-
ment of Science and Technology and the National Research
Foundation (South Africa) for financial support.
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z Crystal data for 1ꢀMeOH: C49H28N6O7, M = 812.77, colorless plate,
3
ꢀ
0.35 ꢃ 0.31 ꢃ 0.22 mm , triclinic, space group P1 (No. 2), a =
9.5852(7), b = 14.1037(10), c = 15.5025(11) A, a = 72.741(1), b =
84.113(1), g = 85.594(1)1, V = 1988.4(2) A3, Z = 2, Dc = 1.357 g
cmꢂ3, F000 = 840, CCD area detector, MoKa radiation, l = 0.71073
A, T = 100(2) K, 2ymax = 56.71, 23372 reflections collected, 9236
unique (Rint = 0.0476). Final GooF = 1.037, R1 = 0.0551, wR2
=
0.1146, R indices based on 6218 reflections with I 42s(I) (refinement
on F2), 561 parameters, 0 restraints. Lp and absorption corrections
13 A. Jacobs, L. R. Nassimbeni, K. L. Nohako, H. Su and J. H.
Taljaard, Cryst. Growth Des., 2008, 8, 1301.
applied, m = 0.093 mmꢂ1
.
Crystal data for 1ꢀACN: C50H27N7O6, M = 821.79, colorless thin
needle, 0.23 ꢃ 0.11 ꢃ 0.05 mm3, orthorhombic, space group Pbca
(No. 61), a = 26.101(7), b = 11.662(3), c = 27.000(7) A, V =
8218(4) A3, Z = 8, Dc = 1.328 g cmꢂ3, F000 = 3392, CCD area
detector, MoKa radiation, l = 0.71073 A, T = 100(2) K, 2ymax = 50.11,
33775 reflections collected, 7245 unique (Rint = 0.1423). Final GooF =
1.018, R1 = 0.0789, wR2 = 0.1669, R indices based on 4146 reflections
with I 42s(I) (refinement on F2), 569 parameters, 0 restraints. Lp and
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GEGLAF, MUPSEV, NATBUG.
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molecular Chemistry, ed. J. L. Atwood, J. E. D. Davies, D. D.
MacNicol and F. Vogtle, Elsevier Science, Oxford, 1996, vol. 6; (b)
¨
absorption corrections applied, m = 0.090 mmꢂ1
.
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Davies and D. D. MacNicol, Oxford University Press, Oxford,
ꢁc
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