Solid-State Supramolecular Chemistry of a Benzylpyridine-Functionalized Zwitterion: Polymorphism, Interconversion, and Porosity

Article abstract of DOI:10.1021/acs.cgd.5b01238

The reaction between acetylenedicarboxylic acid and 4-benzylpyridine yields two products: a salt and a zwitterion. The relationship between these two products has been investigated, revealing that the salt is the kinetic product of the reaction and the zw

Full text of DOI:10.1021/acs.cgd.5b01238

Article
pubs.acs.org/crystal
Solid-State Supramolecular Chemistry of a Benzylpyridine-
Functionalized Zwitterion: Polymorphism, Interconversion, and
Porosity
Leigh Loots, James P. O’Connor, Tanya le Roex, and Delia A. Haynes*
Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, Republic of South Africa
S
* Supporting Information
ABSTRACT: The reaction between acetylenedicarboxylic
acid and 4-benzylpyridine yields two products: a salt and a
zwitterion. The relationship between these two products has
been investigated, revealing that the salt is the kinetic product
of the reaction and the zwitterion is the thermodynamic
product. The zwitterion has four polymorphs and three
solvates. Interconversion between these forms has been
studied and was shown to be solvent-mediated when it
occurs; conversion between most polymorphic forms cannot
be achieved using thermal methods. The temperature at which
the reaction to form the zwitterion is carried out and the
solvent system used are crucial in determining which
polymorphic form crystallizes from the reaction. In addition,
polymorphic Form I is shown to be porous to dioxane.
ordering of the included guest molecules. These materials are
interesting in part because they are salts: porous solids based on
ionic organic materials are of interest due to the combination of
strong and directional charge-assisted hydrogen bonds with the
flexibility, in terms of dissolution and recrystallization, offered
by organic systems. A series of diamondoid porous organic salts
constructed from triphenylmethylamine and various sulfonic
acids was reported by Tohnai16−19 and co-workers. These
compounds “breathe” in order to exchange guest molecules,
and it was shown that a tunable fluorescent response to various
absorbed guests could be achieved when using a fluorescent
sulfonic acid in the structure. Our research group has also
published work on porous salts based on the pamoate ion,6,20
which have been shown to be porous or highly selective to
certain guest molecules.
Recently, we reported the synthesis and crystallographic
analysis of a series of pyridyl-derived zwitterionic compounds.21
The synthesis of these zwitterions is simple, employing mild
conditions where the products are obtained as single crystals
without further purification. Exploring the potential of these
compounds as supramolecular building blocks is highly
appealing: all of the zwitterions have several hydrogen-bond
donors and acceptors that, due to the unusual shapes of the
molecules, are positioned to form extended hydrogen-bonded
chains or networks. Due to the awkward shape and strong
hydrogen-bonding potential of these zwitterions, we anticipated
INTRODUCTION
■
The occurrence of multiple solid-state forms, including
polymorphs and solvates, is a subject of great interest to
solid-state chemists. A number of reasons have been proposed
as to why particular molecules might exhibit multiple forms in
the solid state. It has been suggested that conformational
flexibility is a significant factor when considering the possibility
of molecules manifesting in different solid-state forms
(polymorphs, hydrates, solvates, etc.),1−3 as flexible molecules
make use of multiple pathways of self-organization or self-
assembly.4 Different crystallization conditions, such as solvent,
temperature, and humidity, as well as the crystallization method
(cooling, slow evaporation, from a melt or by sublimation) can
influence the formation of different polymorphs.5 Because
molecules tend to close-pack in the solid state, structural
flexibility and bulky substituents can also affect the solid-state
behavior of a molecule.6 Awkwardly shaped molecules have
more difficulty packing efficiently, and this can lead to
polymorphism, guest inclusion, void space, or porosity in the
resulting crystal structure.
Porosity can be “engineered” by designing framework
materials such as metal−organic framework (MOFs) or
covalent−organic framework (COFs) materials, which employ
coordination or covalent bonds, respectively, to construct the
framework. Hydrogen-bonded organic framework materials are
relative newcomers to the field of porosity, first introduced by
Wuest7−9 and co-workers. Ward10−15 and co-workers followed
soon after with a series of guanidinium sulfonate framework
materials that show potential in second-order harmonic
generation and nonlinear optical properties due to polar
Received: August 26, 2015
Revised: October 23, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.cgd.5b01238
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Article
Scheme 1. Synthesis of Zwitterion 1 and Salt 2
Table 1. Selected Crystallographic Data for the Different Forms and Solvates of 1 as well as for Salt 2
structure
Form I
THF or
acetone
Form II21
Form III
Form IV
1Diox
1Benz
1MeOH
salt (2)
crystallization solvent
1Diox immersed acetone/p-
in MeOH/
H2O
water (recryst.) dioxane
benzene/
MeOH
CH2Cl2/
MeOH
MeCN
xylene
formula weight
crystal symmetry
space group
a (Å)
283.27
283.27
283.27
monoclinic
P21/c
282.28
orthorhombic
Pbca
327.32
monoclinic
P21/n
322.33
monoclinic
P21/n
292.20
monoclinic
P21/n
226.25
monoclinic
P21/n
monoclinic
P21/n
orthorhombic
Pbca
13.801 (5)
7.407 (3)
14.537 (6)
90
15.143 (1)
7.687 (1)
22.303 (2)
90
8.197 (3)
6.208 (2)
26.752 (9)
90
8.661 (2)
8.262 (2)
36.966 (8)
90
13.882 (2)
7.442 (1)
15.134 (3)
90
13.870 (4)
7.451 (2)
15.204 (4)
90
13.935 (1)
7.410 (1)
14.532 (1)
90
5.390 (3)
8.680 (4)
25.258 (1)
90
b (Å)
c (Å)
α (deg)
β (deg)
γ (deg)
97.369 (6)
90
90
92.374 (4)
90
90
96.588 (2)
90
96.399 (4)
90
97.066 (1)
90
95.143 (7)
90
90
90
Z
4
8
4
8
4
4
4
4
V (Å3)
1473.8 (1)
100 (2)
1.277
2596.1 (3)
100 (2)
1.450
1360.1 (8)
100 (2)
1.383
2645.1 (9)
296 (2)
1.423
1553.1 (5)
100 (2)
1.400
1561.5 (7)
100 (2)
1.371
1.489.2 (2)
100 (2)
1.300
1176.9 (1)
296 (2)
1.277
temp. (K)
Dcalcd (g·cm−1
Ntotal
)
8972
15 206
3070
8231
11 543
2385
9203
9242
32 614
3407
7165
Nind
3392
3102
3569
3523
2648
Nobsd
2857
2711
2325
1521
2930
1989
2794
1776
R1 [I > 2α(I)]
0.042
0.0379
0.0222
0.0973
1.019
0.0437
0.0379
0.0939
1.055
0.0592
0.0656
0.1305
1.051
0.0485
0.0224
0.1234
1.045
0.0617
0.0695
0.1418
1.037
0.0465
0.0390
0.1231
1.045
0.0444
0.0233
0.1082
1.036
Rint
0.0285
0.1053
1.038
wR2
GOF
μ (mm−1
)
0.093
0.105
0.100
0.103
0.103
0.097
0.095
0.086
a
void volume (Å3)
21.3 (1.5)/
28.7 (1.4)
N/A
N/A
N/A
146.2 (1.5)/
151.7 (1.4)
146.8 (1.5)/
151.195 (1.4)
24.44 (1.5)/
68.78 (1.4)
N/A
b
Squeeze28 (1.2 Å probe)
(void volume, electrons
per void)
65 Å; 3 e
N/A
N/A
N/A
145 Å; 44 e
142 Å; 40 e
58 Å; 11 e
N/A
a
Void volume was determined as contact surface using MSRoll;29 probe radius, in angstroms, is given in parentheses. For solvates, this is the volume
b
of the void if the solvent is deleted, in other words, the volume of the space occupied by the solvent. Void volume was calculated using the averaged
structure of the disorder model.
that they might prove to be good building blocks for organic
hosts or porous materials. It also seemed possible that they
would exhibit a variety of solid-state forms. Polymorphism in
zwitterionic systems has been investigated previously, with the
majority of these studies focusing on drug compounds or amino
acids.22−27
solvates (1,4-dioxane, benzene, and MeOH) and four
polymorphic forms of 1 have been obtained from solution
crystallization methods. (We have used the term polymorphs to
describe these four forms despite the fact that some contain the
cis isomer of the molecule and some contain the trans isomer.
We have observed solvent-mediated conversion between a cis-
containing form and a trans-containing form, so the term
polymorphs is applicable.) This article describes these forms, as
well as the investigation of the relationships between them. In
addition to an analysis of the structures of the various forms of
zwitterion 1 and the relationships between these forms, we also
report the characterization of a new ionic hydrogen-bonded
porous material, Form I of 1. As discussed above, the only
porous ionic materials reported in the literature to date are the
diamondoid porous organic salts (dPOS) reported by
Tohnai16−19 and the porous pamoate salts reported by our
group.6,20 Form I of 1 is thus a rare example of a porous ionic
organic material.
Several of the zwitterions reported in our previous study21
have been further investigated, and, in this article, we report the
detailed study of (2Z)-2-(4-benzylpyridinium-1-yl)-3-carboxy-
1-hydroxyprop-2-en-1-olate, 1 (Scheme 1).
The synthesis of 1 proceeds via reaction of acetylenedi-
carboxylic acid (ADC) and 4-benzylpyridine (4BP) in solution.
Our previous study briefly reported three forms for 1: two
polymorphs and a dioxane solvate. The crystal structure of one
of the polymorphs was also described (CCDC refcode
BIXNON no. 987549).21 Further investigation of this
zwitterion in the solid state has yielded interesting solvent
inclusion as well as polymorphic behavior. A related salt, 2, was
also obtained from the same starting materials. To date, three
B
DOI: 10.1021/acs.cgd.5b01238
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Article
structure or evidence of conversion to any of the other solid-
state forms).
RESULTS AND DISCUSSION
■
Zwitterion 1 is synthesized by direct reaction of the starting
materials in solution (Scheme 1). Crystal structures of several
forms of 1 have been obtained, as well as the crystal structure of
salt 2. Crystallographic data are summarized in Table 1, and
hydrogen-bonding distances and angles are tabulated in the
Supporting Information. To date, zwitterion 1 has been shown
to crystallize in four different polymorphic modifications,
depending on the reaction solvent (Table 1 and Experimental
Section). Three of these polymorphs contain the zwitterion in
the trans conformation (Figure 1a); one contains the cis isomer
(Figure 1b). One of these, herein Form II, has been described
in detail previously,21 but it will be discussed briefly here for
comparative purposes. The crystal structures of 1 and its
solvates, as well as salt 2, are described first. This is followed by
a discussion of the relationship between the zwitterion and the
salt and then a description of investigations into conversion
between the different solid state forms.
It is important to note that 1 is insoluble in most organic
solvents; thus, most of the products reported crystallize directly
from the reaction mixture and have not been recrystallized.
Polymorphs of 1. Form I of zwitterion 1 crystallizes from
acetone or tetrahydrofuran in space group P21/n, with one
molecule of 1 in the trans conformation in the asymmetric unit
(Figure 1a). Hydrogen-bonded chains of molecules interdigi-
tate in a herringbone pattern (Figure 2). The benzylpyridine
moieties are twisted and bent at the methylene bridge, with a
dihedral angle of 79.87(7)° between the two ring planes (angle
at methylene = 114.01°).
A notable and unusual feature of Form I is the small pockets
of open space in the structure, which have a volume of 21.3 Å3
when using a probe with radius 1.5 Å (Figure 2b). This is
reflected in the lower calculated density of Form I (Table 1).
Thermogravimetric analysis (TGA) and Squeeze28 results have
confirmed that the voids are empty (see Supporting
Information). It is very unusual for there to be open space
within a crystal structure, and this is especially interesting since
three close-packed polymorphs of 1 have been obtained under
very similar conditions (vide infra). Of further interest is the
fact that this open form appears to be quite stable under
atmospheric conditions; it can be left under ambient conditions
on the open bench for at least 6 days without any observable
change in form (some samples have been kept on the open
bench for up to a year without any observable change in
Form II21 of zwitterion 1 crystallizes in orthorhombic space
group Pbca, with one zwitterion in the trans conformation in
the asymmetric unit. As in Form I, the zwitterions hydrogen
bond to one another via the carboxylate moieties to form one-
dimensional chains. Two such chains are positioned alongside
one another in a slightly offset fashion. These pairs of chains
stack one on top of another along [001] to form bilayers, which
are then stacked antiparallel with one another along [100]
(Figure 3).
Form III crystallizes in monoclinic space group P21/c, with
one molecule of 1 in the cis conformation (Figure 1b) in the
asymmetric unit. There is no intermolecular hydrogen bonding
in this structure, there are only intramolecular hydrogen bonds
between the carboxylic acid and carboxylate moieties, which
arise due to the cis conformation of the alkene moiety. The
pyridyl and phenyl rings in each molecule are twisted so as to
be approximately perpendicular to one another. Molecules pack
alongside one another such that the ionic groups stack and the
phenyl groups stack. This results in hydrophobic and
hydrophilic bands in the structure (Figure 4).
Reactions to synthesize 1 also often yield a fourth
polymorph, Form IV. This form is obtained from reactions in
MeOH, despite the existence of a MeOH solvate (vide infra),
which was obtained once from a DCM/MeOH mixture.
Microanalysis, NMR, and mass spectrometry confirmed that
Form IV contained zwitterion 1; this was necessary due to the
difficulty experienced in obtaining single crystals of this form.
Single crystals of Form IV were eventually obtained by
recrystallization of the powdered product (obtained by reaction
in MeOH) from water. This form crystallizes in orthorhombic
space group Pbca, with one molecule of 1 in the asymmetric
unit. The zwitterion is in the trans conformation, as in Forms I
and II; however, the hydrogen-bonding motif is considerably
different. The hydrogen bonds between the carboxylate and
carboxylic acid moieties have an angle that is quite different,
resulting in a zigzag chain with the benzylpyridine moieties
projecting outward. The chains pack one on top of another in
an offset manner. The phenyl moieties of neighboring chains
interdigitate to form a herringbone motif. The molecules of 1
are bent at the methylene bridge (113.1°), with a dihedral angle
of 69.28(8)° between the pyridyl and phenyl rings (Figure 5).
Solvates of 1. To date, three solvates of 1 have been
characterized. Two of these (the dioxane and benzene solvates)
are isostructural to one another and bear a close relationship to
Form I of 1 (the open form). The methanol solvate is
isostructural to Form I, but it contains MeOH in the voids.
1Diox crystallizes in monoclinic space group P21/n, with one
zwitterion and one-half a molecule of 1,4-dioxane in the
asymmetric unit. The zwitterion is in the trans form, and the
benzylpyridine moiety is bent (113.8°) at the methylene bridge
such that the aromatic rings are at an angle of 58.36° to one
another. Once again, one-dimensional chains are formed via
hydrogen bonding between carboxylate groups. Parallel chains
are arranged into layers separated by dioxane molecules (Figure
6a). The guest molecules occupy small pockets surrounded by
eight molecules of 1. Pockets were mapped with MsRoll29 using
a 1.5 Å probe radius and are approximately 146.2 Å3 in volume.
When the guest molecule is viewed along with the mapped
voids, it is clear that the oxygen atoms of the 1,4-dioxane
molecules are protruding out of the contact surface, indicating
that there are close contacts between these atoms and
Figure 1. (a) Trans isomer of 1, as seen in Form I. (b) Cis isomer of 1,
as seen in Form III.
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Figure 2. Packing in Form I. (a) Hydrogen-bonded chains of zwitterions. (b) Packing diagram viewed along [010], with voids shown in yellow
(voids mapped using MsRoll29 with a probe radius of 1.5 Å).
any significant intermolecular interactions between the host and
the guest in 1Benz (as were observed for 1Diox) but, rather, a
size−shape match that allows the benzene molecule to be
included. The pockets occupied by the benzene guests were
mapped using a probe radius of 1.5 Å (in MsRoll) and have a
volume of 146.8 Å3 (Figure 7b). TG analysis shows a 12.6%
weight loss starting at approximately 50 °C, which corresponds
to one-half of a benzene molecule per zwitterion (calculated
mass loss for one-half of a benzene = 12.11%).
Crystallization from DCM/MeOH yielded crystals of 1MeOH
on only one occasion. This solvate is isostructural to Form I,
but MeOH is included in the void. (Crystallization from pure
MeOH yields Form IV, vide supra.) 1MeOH crystallizes in space
group P21/n, with one molecule of 1 and one partially occupied
molecule of MeOH in the asymmetric unit. The benzyl moiety
of 1 is disordered over two positions of approximately equal
occupancy. The methylene bridge angles are 112.54° and
116.16° for the two disordered positions, respectively. The
dihedral angles between the aromatic rings are 76.3(2)° and
80.8(3)°. In the single crystal structure, the guest MeOH is just
over 25% occupied, but TGA of a bulk sample indicates one
molecule of guest per molecule of 1 (mass loss 10.5%;
calculated mass loss = 10.15%). This mass loss starts at ambient
temperature, so we assume MeOH was lost from the single
crystal before data collection. The increase in mass loss above
what is expected for one molecule of MeOH per molecule of 1
could be due to surface solvent. We have been unable to verify
this experimentally because we were unable to obtain further
Figure 3. (a) Hydrogen-bonded chains in Form II. (b) Packing in
Form II viewed down [010].
samples of 1MeOH
.
An overlay of the structures of Form I and 1MeOH is shown in
Figure 8. It is clear that the MeOH guests in 1MeOH reside in
what are open pores in Form I, although the void volume in the
MeOH solvate is slightly larger (Table 1).
Crystal Structure of Salt 2. Salt 2 crystallizes in
monoclinic space group P21/n and contains one 4-benzylpyr-
idinium cation and one-half of an acetylenedicarboxylate
dianion in the asymmetric unit. The angle at the methylene
bridge in the cation is 109.84°, and the carboxylate oxygen
atoms are disordered over two positions of equal occupancy.
Each dianion hydrogen bonds to two cations, forming a three-
component S-shaped adduct (Figure 9a). The three-membered
adducts stack in an offset manner along the [010] direction
such that the pyridyl moieties are aligned with the acetylene
moiety of the next S-shaped unit in the stack. These stacks then
pack in a herringbone arrangement perpendicular to the (102)
plane (Figure 9b) to form two-dimensional layers. The layers,
in turn, pack one on top of another along [100].
Figure 4. Packing of Form III viewed along [010].
neighboring zwitterions (Figure 6b). TG analysis shows a
13.4% weight loss commencing at approximately 85 °C, which
correlates well with the mass loss expected for one-half of a
dioxane molecule per zwitterion (calculated mass loss =
13.45%).
The solvate including benzene (1Benz) is isostructural to 1Diox
.
When these two structures are overlaid using Mercury30
(Figure 7a), it is clear that the conformation of the zwitterion in
the two structures is essentially identical. The guest molecules
occupy the same position in the two structures, but they have
different orientations in the pockets. There do not appear to be
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Figure 5. (a) Hydrogen-bonded chain in Form IV viewed down [010]. (b) Packing of IV viewed along [100].
Figure 6. (a) Hydrogen-bonded chains of zwitterions in 1Diox. (b) Solvent pockets viewed down [010], with dioxane guests shown in space filling
representation. Void space (contact surface) if the solvent is removed is shown in yellow.
Figure 7. (a) Overlay of the zwitterions from 1Diox (red) and 1Benz
(yellow). (b) Solvent pocket in 1Benz
.
Figure 9. (a) S-shaped hydrogen-bonded units formed in salt 2. (b)
Packing of 2 viewed along (102).
Relationship between the Zwitterion and the Salt.
Both zwitterion 1 and salt 2 are obtained by mixing ADC and
4BP in solution (Scheme 1). At first, it seemed that synthesis of
zwitterion 1 was not reproducible, as, on some occasions, salt 2
was obtained. It seemed possible that one of the products
would be a kinetic product, so the effect of temperature on the
product of the reaction was assessed.
Reflux of a 1:1 molar ratio of ADC and 4BP at 75 °C in THF
favors nucleophilic addition of the pyridyl to the alkyne moiety,
resulting in the isolation of Form IV of zwitterion 1. Salt 2
could be reproducibly obtained by heating the reaction mixture
until the components were dissolved and then placing the vial
Figure 8. (a) Overlay of the zwitterions in 1MeOH (green) and Form I
(red). (b) Overlay of the packing of 1MeOH (green) and Form I (red)
viewed down [010]. The calculated voids in Form I are shown in
yellow, with the MeOH guest molecules of 1MeOH shown in green ball-
and-stick model. Voids were (in this instance) calculated in Mercury30
using a probe radius of 1.2 Å.
E
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in the refrigerator (−9 °C) to crystallize. It seems clear that the
zwitterion is the thermodynamic product of this reaction,
whereas the salt is the kinetic product.
does not proceed in a single-crystal-to-single-crystal fashion.
The resulting material retains its crystallinity, as is evident from
PXRD (see Supporting Information), but no single crystals
suitable for X-ray diffraction experiments remain.
Refluxing salt 2 with additional ADC or refluxing just salt 2
under the same conditions (THF at 75 °C) also yields Form IV
of the zwitterion. Refluxing ADC and 4BP in THF at 63 °C
gave a mixture of zwitterion Forms I and IV, whereas reflux at
45 °C gave Form I. This indicates that, while the zwitterion is
the thermodynamic product of the reaction between ADC and
4BP, the particular solid-state form that is obtained is
temperature-dependent.
The conversion of 1Diox to Form I was also investigated.
Crystals of 1Diox exposed to the air for an extended period (10
days) showed partial conversion from the solvate to Form I.
Conversion of 1Diox to Form I was confirmed using variable-
temperature PXRD (VT-PXRD), which shows conversion of
the solvate to Form I starting at approximately 60 °C (Figure
11). Because the bulk sample used for PXRD analysis may not
have been pure solvate (there may have been some Form I
present), this conversion was also studied in a single crystal: a
single crystal of 1Diox was placed on the diffractometer, and a
unit cell was determined at 25 °C. The crystal was then heated,
and unit cells were determined at various temperatures.
Between 60 and 70 °C, the unit cell parameters changed to
those of Form I (see Supporting Information for full details).
The crystal had deteriorated to such an extent by the end of the
experiment that, although a unit cell could be obtained, a full
data set could not be collected; conversion of 1Diox to Form I is
also not a single-crystal-to-single-crystal process.
It was also shown using PXRD that the conversion between
Form I and 1Diox is reversible: if Form I is exposed to dioxane,
then it converts to 1Diox, and the same sample then converts
back to Form I on heating (Supporting Information Figure
S14). It is clear from these results that Form I of zwitterion 1 is
porous to dioxane. Future work will involve a detailed
investigation of the potential of Form I as a porous material.
An examination of the structures of Form I and 1Diox reveals
that the two structures are very closely related. The packing
arrangements are essentially the same; however, in the solvate,
the hydrogen-bonded chains of zwitterions are slightly farther
apart, and the conformation of the zwitterion has changed
slightly. The structure of Form I opens up to accommodate the
solvent molecules. Figure 12 makes the relationship between
the structures clear.
Mechanochemical reaction of a 1:2 molar ratio of ADC and
4BP, both neat and liquid-assisted (dioxane, benzene, acetone),
yields salt 2.
Transformation between the Forms of 1. The
observation of so many solid-state forms of 1 prompted the
question of whether conversion between these various forms
would be possible. Our first question was whether conversion
between Form I and the dioxane or benzene solvates was
possible. In order to test this, Form I was exposed to vapors of
the solvents or immersed directly in the solvent in question.
When Form I is immersed in dioxane or benzene, the crystals
remain unchanged after 6 days. However, after 10 days in
dioxane, or exposed to dioxane vapor, both PXRD and TGA
show that the crystals of Form I have converted to 1Diox (see
Supporting Information for data). For complete conversion
from Form I to the dioxane solvate, a 13% mass loss is expected
for TGA. After 10 days immersed in dioxane, the powdered
sample shows a mass loss of approximately 12%, indicating
almost complete conversion. Powdered Form I exposed to
dioxane vapor shows only a 4% mass loss after 10 days,
indicating that conversion in this case is much slower. The
same experiments were attempted with benzene; however, no
significant uptake of benzene had occurred after 10 days.
In order to further investigate the uptake of dioxane by Form
I, crystals of Form I immersed in dioxane were photographed
for several days. After 1.5 days, the crystals were still Form I.
After 2 days, the crystals started to darken (Figure 10). After 10
days, the crystals were completely dark and did not diffract. It is
clear from these experiments that uptake of dioxane by Form I
This close relationship between the structures makes it
unsurprising that Form I is able to take up dioxane while none
of the other forms show conversion to the solvate. What is
somewhat surprising is that Form I does not seem to take up
other solvents into these voids to any appreciable extent.
In order to confirm this, Form I was immersed in a variety of
solvents. The results are given in detail in the Supporting
Information, Table S10. In summary, when crystals of Form I
Figure 11. Variable-temperature PXRD showing the conversion of
1Diox to Form I. The sample was heated from 20 to 90 °C and then
cooled to room temperature. PXRD patterns were recorded every 10
°C until 60 °C and then every 5 °C.
Figure 10. Images of crystals of Form I immersed in dioxane (a) at the
start of the experiment and (b) after 2 days.
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Figure 12. Comparison between the packing in Form I (a) and 1Diox (b). Dioxane molecules are colored green.
are exposed to smaller guests such as water or methanol, the
crystals become opaque or dissolve after 24 h. The micro-
crystalline product obtained after exposure to water was
subjected to PXRD analysis, and it was confirmed that Form
I had converted to Form II. This process appears to be
irreversible; crystals of Form II were immersed in a variety of
solvents, and PXRD confirmed no change when Form II was
immersed in acetone, THF, p-xylene, benzene, or 1,4-dioxane
for 5 days (Supporting Information, Table S11). However,
further experiments showed that Form II does convert to Form
IV when it is immersed in MeOH (dried on molecular sieves)
for 5 days. Dissolving crystals of 1Diox in a MeOH/water
mixture, in the presence of pyrazine, also gave crystals of Form
II.
Figure 13. Conversion between the various solid-state forms described
in this article.
Further investigation into whether any change in form was
observed when crystals of Forms I−IV are immersed in various
solvents was carried out. These results are detailed in the
Supporting Information, Tables S11−S13. It was found that
immersing Form I in DMF or methanol yields Form IV. Form
II converts to Form IV if it is immersed in MeOH, but it
remains unchanged when it is exposed to other solvents. Form
III converts to Form IV when it is immersed in a range of
solvents. Form IV shows no evidence of conversion to other
forms. From these results, it appears that Form IV is the most
stable form of 1.
Thermal Analysis. In order to further investigate the
relationships among Forms I−IV, differential scanning
calorimetry (DSC) was carried out on the various forms of 1.
Of Form I, II, or IV, none shows any thermal events before
decomposition. It seems that conversion between these forms
takes place only when it is solvent-mediated.
The DSC of Form III shows a broad endotherm before 100
°C. It seems probable that this is due to conversion to Form IV
(vide supra), and this has largely been confirmed by PXRD,
although it has proven to be difficult to obtain sufficiently
crystalline bulk material to record quality PXRD patterns (see
Supporting Information).
DSC of salt 2 shows an endotherm followed by a large
exotherm before 100 °C. Observation of a sample using a
conventional melting point apparatus, combined with analysis
of the TGA data, confirms that this is due to melting followed
by decomposition.
CONCLUSIONS
■
Reaction between acetylenedicarboxylic acid and 4-benzylpyr-
idine yields two products. The kinetic product, reproducibly
obtained from crystallizations at low temperatures, is a salt (2),
which has been structurally characterized. The thermodynamic
product, obtained when the reaction is carried out at higher
temperatures, is a zwitterion, (2Z)-2-(4-benzylpyridinium-1-yl)-
3-carboxy-1-hydroxyprop-2-en-1-olate (1). Salt 2 can be
converted to 1 by reflux at elevated temperatures.
Four polymorphs and three solvates of 1 have been
characterized and described. Form I is porous to dioxane,
yielding a dioxane solvate. The MeOH and benzene solvates are
also closely related to Form I, but they could not be obtained
by exposing Form I to solvent. Conversion between the
dioxane solvate and Form II, or Form I and Form II, appears to
be solvent-mediated. Crystallization of Form I, III, or IV from a
reaction mixture is both temperature- and solvent-dependent.
Analysis of the conversions between the various forms suggests
that Form IV is the most stable form: Forms I−III all convert
to Form IV, but Form IV has shown no evidence of conversion
to any of the other forms.
It was anticipated that the unusual shape of zwitterion 1
would result in interesting solid-state supramolecular chemistry.
It is clear from the number of forms obtained thus far that this
is most certainly the case.
EXPERIMENTAL SECTION
■
Form I of (2Z)-2-(4-benzylpyridinium-1-yl)-3-carboxy-1-hydroxyprop-
2-en-1-olate (1) was obtained by mixing ADC (0.020 g, 0.175 mmol)
and 4BP (0.030 g, 0.177 mmol) in either acetone (2 mL),
tetrahydrofuran (2 mL), or a mixture of toluene (2 mL) and MeOH
(0.5 mL) with stirring and gentle heating. When the components were
completely dissolved, the solution was set aside and colorless crystals
were afforded after a few days. Form I can also be obtained by
DSC and TGA results for Forms I−IV, salt 2, and the three
solvates of 1 are included in the Supporting Information.
The relationship between the various forms is summarized in
Figure 13.
G
DOI: 10.1021/acs.cgd.5b01238
Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design
Article
exposing the dioxane solvate (1Diox) to the air for approximately 3
weeks. The dioxane solvate (1Diox) was obtained by mixing ADC
(0.020 g, 0.175 mmol) and 4-benzylpyridine (0.030 g, 0.177 mmol) in
1,4-dioxane (1−2 mL). The solution is colorless when the components
first dissolve, but it turns a murky gray and then orange and a dark
green; however, the resulting crystals are colorless. The benzene
solvate (1Benz) was obtained by mixing ADC (0.020 g, 0.175 mmol)
and 4BP (0.030 g, 0.177 mmol) in a benzene/MeOH (1 mL/0.5 mL)
mixture. The colorless crystals are extracted from a dark brown
solution. Crystals grown from an acetone/benzene mixture (1:1 molar
approximately 200 °C (depending on the Tdec obtained from TGA) at
a heating rate of 10 °C/min and a cooling rate of 5 °C/min. This was
performed using nonhermetically sealed aluminum pans with a pinhole
in the lid.
Thermogravimetric analysis was carried out using a TA Instruments
Q500 system under a N2 gas purge using aluminum sample pans at a
ramp rate of 10 °C/min.
Images of Form I Crystals Exposed to Dioxane. Crystals of
Form I were placed in a short glass vial and covered with
approximately 3 mL of 1,4-dioxane. The glass vial was covered with
a glass slide to prevent excessive evaporation of the solvent, and the
crystals were filmed for 2 days with a Leica Microsystems microscope
camera (DFC295). Images were taken every 30 min, and the solvent
level was kept constant during the 2 days. After 1.5 days, the crystals
had not yet started to darken. SCD analysis showed that all of the
crystals selected for SCD analysis were still Form I. Exchange for 1,4-
dioxane had, therefore, not yet taken place. By day two, the crystals
had started to darken.
In a further experiment, crystals of Form I were photographed for
10 days with a Leica Microsystems microscope camera (DFC295).
Images were taken every 30 min for the first 2 days, and for the
remaining time, images were taken every hour. The solvent level was
kept constant during the 10 days. Between days 2 and 3, the crystals
started to darken, and by day 10, the crystals were nearly completely
dark. After 10 days, the crystals were removed from the mother liquor
for single-crystal X-ray diffraction analysis, but the crystals were very
brittle and did not diffract.
ratio) gave similar unit cell parameters. The methanol solvate (1MeOH
)
was obtained by dissolving ADC (0.044 g, 0.386 mmol) and 4BP
(0.075 g, 0.443 mmol) in a dichloromethane/MeOH (4 mL/a few
drops) mixture, which was stirred at 60 °C for approximately 5 min
and then left to crystallize. Colorless crystals were obtained from a
clear pink solution.
Form II21 was obtained by dissolving 1Diox (0.020 mg, 0.070 mmol)
in H2O (1 mL) and combining this with pyrazine (0.011 g, 0.137
mmol) or pyridine (0.011 mg, 0.139 mmol) dissolved in MeOH (1
mL), with heating and stirring. The solution was then set aside to
crystallize. Form III was obtained by mixing ADC (0.040 g, 0.350
mmol) with 4-benzylpyridine (0.060 g, 0.355 mmol) in a mixture of
acetone and p-xylene (1:1 molar ratio, 2 mL/4.2 mL) with stirring and
gentle heating. The mixture was allowed to cool, and crystals were
obtained after a few days. Form IV was obtained from the combination
of ADC (0.040 mg, 0.350 mmol) and 4BP (0.060 mg, 0.355 mmol) in
MeOH (3 mL) with heating and stirring. A white precipitate was
formed within a few hours. This powder was then recrystallized from
water; colorless plates were obtained.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.cgd.5b01238.
■
Salt 2 was obtained from the reaction of ADC (0.040 g, 0.350
mmol) and 4-benzylpyridine (0.060 g, 0.355 mmol) combined in
acetonitrile (2 mL) with gentle heating and stirring. Once all
components were dissolved, the solution was allowed to cool to
room temperature (or placed in the refrigerator), which yielded
colorless crystals after a few days. Crystals were also obtained from
acetone, EtOH, and THF when solutions were crystallized at low
temperature.
S
TGA, DSC, and PXRD data and selected hydrogen-
bonding tables (PDF)
X-ray crystallographic information files (CIF)
CCDC 1420454−1420460 contain the supplementary crystal-
lographic data for this article. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
X-ray Diffraction. Single-crystal X-ray intensity data were collected
on a Bruker SMART Apex II X-ray diffractometer equipped with a Mo
(λ = 0.71073 Å) fine-focus sealed tube and a 0.5 mm MonoCap
collimator. The data for 1MeOH was collected on an Apex Duo Quazer
with Incotec Iμs Mo (λ = 0.71073 Å) source. Data were captured with
a CCD (charge-coupled device) area detector. Unless stated otherwise,
data collections were carried out at 100 K using an Oxford
Cryosystems cryostat (700 series Cryostream Plus) attached to the
diffractometer. Data collection and reduction were carried out using
the Bruker software package APEX2,31 using standard procedures. All
structures were solved and refined using SHELX-201332 employed
within the X-Seed33,34 environment. Diagrams were generated using
POV-Ray,35 except for overlays, which were calculated in Mercury.
PXRD patterns were collected using a PANalytical X’Pert Pro
diffractometer with Bragg−Brentano geometry using Cu Kα radiation
(λ = 1.5418 Å) at 45 kV and 40 mA. Standard samples were run using
a reflection-transmission spinner stage using a zero-background sample
holder, and samples were spun at 4 revolutions per second. Intensity
data were captured with an X’Celerator detector with 2θ scans
performed in the range 5−50° with a 0.0167 step size. Some patterns
were collected using a Bruker D2 Phaser diffractometer with (Bragg−
Brentano geometry) using Cu Kα radiation (λ = 1.5418 Å) at 30 kV
and 10 mA. Intensity data were captured with a Lynxeye detector with
2θ scans performed in the range 4−40° with a 0.016° step size.
Samples were spun at 30 rpm.
AUTHOR INFORMATION
Corresponding Author
*Tel.: +27 21 808 3358. E-mail: dhaynes@sun.ac.za.
■
Notes
Any opinion, findings, and conclusions or recommendations
expressed in this material are those of the authors and therefore
the NRF does not accept any liability in regard thereto.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to Helene Wahl for collecting the images of
Form I crystals. We acknowledge the National Research
Foundation of South Africa and Stellenbosch University for
funding and the Claude Leon Foundation for a postdoctoral
fellowship.
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