Structural and energetic landscape of fluorinated 1,4-phenylenediboronic acids

Article abstract of DOI:10.1021/cg3005272

The results of X-ray crystallographic and computational studies of a series of fluorinated 1,4-phenylenediboronic acids (i.e., fluoro-1,4- phenylenediboronic acid, 2,6-difluoro-1,4-phenylenediboronic acid, 2,3-difluoro-1,4-phenylenediboronic acid, 2,5-difluoro-1,4-phenylenediboronic acid, and tetrafluoro-1,4-phenylenediboronic acid) are reported. The effect of fluorine substitution on crystal organization in the presence of strong and directional hydrogen bonds was studied. Comparison with the two previously reported forms of the unsubstituted 1,4-phenylenediboronic acid revealed a strong relation between a supramolecular network and the number of water molecules present in the crystal lattice. As indicated by the theoretical calculations performed in the CRYSTAL and PIXEL programs, the structures with greater amount of water are better stabilized (from about -170 kJ?mol ^-1 for anhydrous forms to about -420 kJ?mol^-1 for tetrahydrate). The energy of hydrogen bonded dimers vary from -40 kJ?mol^-1 to -50 kJ?mol^-1. Contacts with fluorine atoms play rather a secondary role in the crystal packing. Fluorine substituents tend to interact with the electropositive boron atom. Furthermore, intramolecular interactions significantly affect the torsion angle of the B(OH)₂ group. The constrained energy scan revealed that stronger interactions with substituents stabilize the planar conformation and hamper the rotation of the boronic group. This in turn has a further impact on the interactions within selected crystal motifs and supposedly rules the proton disorder within boronic fragments. Besides the interactions with the fluorine atoms, other weak contacts such as C(π)???B and O???B also influence the molecular organization. The energy of the corresponding dimers varies from -15 kJ?mol^-1 to -25 kJ?mol^-1.

Full text of DOI:10.1021/cg3005272

Article
pubs.acs.org/crystal
Structural and Energetic Landscape of Fluorinated
1,4-Phenylenediboronic Acids
Published as part of the Crystal Growth & Design virtual special issue In Honor of Prof. G. R. Desiraju
Krzysztof Durka,*,‡,§ Katarzyna N. Jarzembska,†,§ Radosław Kaminski,† Sergiusz Lulinski,‡
́
́
Janusz Serwatowski,‡ and Krzysztof Wozniak*,†
́
†Department of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warszawa, Poland
‡Department of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664, Warszawa, Poland
S
* Supporting Information
ABSTRACT: The results of X-ray crystallographic and computa-
tional studies of a series of fluorinated 1,4-phenylenediboronic acids
(i.e., fluoro-1,4-phenylenediboronic acid, 2,6-difluoro-1,4-phenylene-
diboronic acid, 2,3-difluoro-1,4-phenylenediboronic acid, 2,5-difluoro-
1,4-phenylenediboronic acid, and tetrafluoro-1,4-phenylenediboronic
acid) are reported. The effect of fluorine substitution on crystal
organization in the presence of strong and directional hydrogen
bonds was studied. Comparison with the two previously reported
forms of the unsubstituted 1,4-phenylenediboronic acid revealed a
strong relation between a supramolecular network and the number of
water molecules present in the crystal lattice. As indicated by the
theoretical calculations performed in the CRYSTAL and PIXEL
programs, the structures with greater amount of water are better
stabilized (from about −170 kJ·mol−1 for anhydrous forms to about −420 kJ·mol−1 for tetrahydrate). The energy of hydrogen
bonded dimers vary from −40 kJ·mol−1 to −50 kJ·mol−1. Contacts with fluorine atoms play rather a secondary role in the crystal
packing. Fluorine substituents tend to interact with the electropositive boron atom. Furthermore, intramolecular interactions
significantly affect the torsion angle of the B(OH)2 group. The constrained energy scan revealed that stronger interactions with
substituents stabilize the planar conformation and hamper the rotation of the boronic group. This in turn has a further impact on
the interactions within selected crystal motifs and supposedly rules the proton disorder within boronic fragments. Besides the
interactions with the fluorine atoms, other weak contacts such as C(π)···B and O···B also influence the molecular organization.
The energy of the corresponding dimers varies from −15 kJ·mol−1 to −25 kJ·mol−1.
cages, polymers, and porous covalent organic frameworks
(COFs).7
1. INTRODUCTION
The understanding of molecular organization in the solid state
enables researchers to control supramolecular entity formation
and to produce crystal networks with desired structural features
and properties. Strong and directional hydrogen bonds, and
many diverse self-complementary hydrogen-bonding groups
(e.g., amide or carboxylic groups), are commonly used for the
purpose of such strategies.1 Recent reports focus on using
the B(OH)2 unit of boronic acids as a building block in the
formation of hydrogen-bonded structures.2 Although boronic
acids are not as commonly studied as carboxylic acids and
amides, numerous applications of these compounds have been
reported.3 For instance, the Suzuki cross-coupling reaction is
one of the most popular methods for carbon−carbon bond
formation.4 Boronic acids are also widely used in medicine, for
example, in antitumor treatment,5 whereas in material science
they act as nonlinear optical chromophores.6 More recently,
boron compounds have been applied in condensation reactions
with polyols to create new functional materials such as macrocycles,
Among the determined crystal structures of various boronic
acids, a great majority forms a dimeric motif of B(OH)2 moieties
(also being characteristic for carboxylic acids and amides).2a−m
Introduction of the second boronic group offers a higher level
of self-assembly by extending the hydrogen-bonded structure in
new directions. Surprisingly, despite some striking examples
found in the literature, diboronic acids have not been well
explored in the context of supramolecular network formation to
date. Up to now, the Cambridge Structural Database (CSD)8
contains only a few structures of diboronic acids.2h−m
Apart from relatively strong hydrogen bonds, as these pre-
sent in the structures of boronic and diboronic acids, also
weaker interactions, for example involving the fluorine atom,
are of current interest in modern supramolecular chemistry.9
Received: April 17, 2012
Revised: May 15, 2012
Published: May 21, 2012
© 2012 American Chemical Society
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Scheme 1. Studied 1,4-Phenylenediboronic Acid Derivatives: 1,4-Phenylenediboronic Acid (noFa4 − tetrahydrate;2l noFb0 −
anhydrous form2m), Fluoro-1,4-phenylenediboronic Acid (mF1), 2,6-Difluoro-1,4-phenylenediboronic acid (26dF1),
2,3-Difluoro-1,4-phenylenediboronic Acid (23dF2), 2,5-Difluoro-1,4-phenylenediboronic Acid (25dF0), and
a
Tetrafluoro-1,4-phenylenediboronic Acid (tF0)
a
The subscript provides information about the water content.
straightforward, which is because highly reactive lithium intermediates
are very susceptible to degradation. After numerous attempts, tF was
finally synthesized by employing a double in situ lithiation/boronation
of a 1,2,4,5-tetrafluorobenzene, using lithium diisopropylamide (LDA)
as lithiating and B(OiPr)3 as boronating agents, respectively. Single-
crystals, suitable for X-ray diffraction experiments, were obtained by
crystallization from various solvent mixtures containing toluene,
acetone, and water. It is worth noting that, although the trifluoro
derivative (C6H5BF3O4) was synthesized, all attempts of crystal
growing were unsuccessful. More detailed information about synthetic
and crystallization procedures is available in the Experimental Section
and Supporting Information.
2.2. Geometries and Energy Computations. Careful structure
determination and preparation were found to be crucial for further
energy analysis and drawing conclusions. Therefore, here we present
the main information regarding methods and proceedings. Full details
of the X-ray diffraction data collection, crystal structure determination,
and theoretical methods are located in the Experimental Section and
Supporting Information.
For the purpose of the molecular and supramolecular structure
analysis and energy computation, all X−H bond distances (X = non-
hydrogen atom) were set to the average neutron values.14 Additionally,
geometry optimization in the CRYSTAL0915 program was performed
to derive more appropriate hydrogen atom positions, that is, not only
X−H bond length but also its direction (see Experimental Section).
Such an approach is crucial for a proper description of interactions
involving hydrogen atoms and thus has a significant impact on lattice
and dimer interaction energy estimation. For instance, the computa-
tional study of two isomorphs, mF1 and 26dF1, based on the X-ray
geometries with X−H bonds simply extended to neutron-normalized
distances, showed a significant cohesive energy difference, which
amounted to over 50 kJ·mol−1 for the benefit of mF1 (Table 2). The
differences between the experimental and optimized crystal structure
of 26dF1 were especially noticeable for the hydrogen atom positions
(Figure 4S in the Supporting Information). The subsequent cohesive
energy calculation and dimer interaction energy estimations gave
values much closer to the results obtained for its isostructural
diboronic acid derivative, mF1, as previously expected.
According to recent reports, the replacement of hydrogen by
fluorine atoms may lead to some distinct changes in-between
initial and resulting crystal structures10 and then is reflected in
the reactivity11 and biological activity of the analyzed com-
pounds.12 A number of studies have been carried out to
establish the role of fluorine atom in crystal engineering,
especially in generating different packing motifs via weak
X−H···F (X = O, N, C), F···F, or F···π interactions.10,11
Nevertheless, the nature of these contacts still remains a matter
of discussion.
In this paper we focus our attention on a series of fluorinated
1,4-phenylenediboronic acid derivatives (Scheme 1). We
discuss their molecular and supramolecular structures, the
role of the water molecules, and the fluorine atom substitution
effect, by comparing the obtained structures with the two
previously reported pseudopolymorphs of 1,4-phenylenedi-
boronic acid: tetrahydrate (noFa4)2l and anhydrous (noFb0)2m
forms. The redistribution of electron density caused by the
fluorine substituent is crucial for weak intermolecular inter-
actions. It influences the geometrical arrangement of boron and
oxygen atoms, and affects the electronic structure of aromatic
rings. Thus, our study is devoted to understanding of binding
properties and the specificity of intermolecular contacts pre-
sent in the investigated systems. For this purpose the X-ray
structural analysis was performed and supplemented by a
comprehensive computational characterization.
2. MATERIALS AND METHODS
2.1. Synthesis. Diboronic acids 26dF and 23dF were synthesized
in accordance with the procedure already published in the literature.13
In turn, the syntheses of mF and 25dF were accomplished using a
double step-by-step lithiation/boronation procedure applied to the
respective bromofluorobenzenes, followed by hydrolysis of the
obtained derivatives (Scheme 2). The synthesis of tF was less
Computational analysis also helped to detect a certain structural
inadequacy in the case of noFa4. Careful study of the literature-
reported noFa4 structure revealed that one of the water molecules
(indicated by the O5 oxygen atom in the CSD file) was incorrectly
oriented. As a consequence, the two symmetry equivalent hydrogen
atoms were found pointing toward each other, being at a very short
distance of about 1.14 Å. This causes some destabilization and
influences the total cohesive energy value. To find a proper arrange-
ment, the full periodic geometry optimization was performed. The
obtained cohesive energy value for the optimized crystal structure
Scheme 2. General Synthetic Scheme of Fluorinated 1,4-
Phenylenediboronic Acids
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Figure 1. Labeling of atoms and the atomic thermal motion estimation as ADPs (50% probability level) for (a) mF1, (b) 26dF1, (c) 25dF0, (d) tF0,
and (e) 23dF2. Site occupancy factors of disordered atoms are given in parentheses. Disordered hydrogen atoms are marked in different colors.
is 36 kJ·mol−1 lower (which corresponds to the energy of a medium
strength hydrogen bond) than that calculated for the reported noFa4
structure, with the X−H bond lengths set to the average neutron
distances.
compare crystal structures and related computational results for the
compounds belonging to each of the previously defined classes.
Subsequently, we confront all the classes and discuss their energetic
landscape in a wider context.
The above-mentioned examples show that not only the X−H bond
lengths, but also their directionality are crucial for a proper hydrogen
bond description, and thus subsequent structural and energetic
studies.16 Averaged neutron-derived X−H bond distances are
approximated and may not be the best estimators for the purpose of
fine-detail hydrogen bonding analysis. Therefore, apart from the X-ray
crystal geometries, we also use the atomic coordinates obtained after
periodic optimization of the studied systems, which, in our opinion,
constitute a more sensible basis for further computational investi-
gations. As a consequence, all presented numerical parameters are
related to the optimized geometries and thus are reported without
estimated standard deviations. In order to validate the CRYSTAL
results, we have also evaluated cohesive energies by the means of the
PIXEL approximation (see Experimental Section).17 PIXEL and
CRYSTAL energy values were found to be consistent. Additionally,
the PIXEL program allows for estimating the total energy components,
which gives an extra insight into the nature of interactions.
The presence of the fluorine substituent has a significant impact on
the structure stabilization and interaction energies within the selected
supramolecular motifs. Hence, in the first part of the discussion, we
compare the molecular geometries of the studied compounds, and
afterward, we systematically analyze their supramolecular structures.
Among the analyzed systems, four basic groups, characterized by a
different amount of solvent incorporated into the crystal lattice, can be
distinguished. These are waterless structures formed by noFb0, 25dF0,
and tF0, then networks containing one (26dF1 and mF1), two
(23dF2), and four (noFa4) water molecules per one molecule of the
diboronic acid. To approach this complex problem, we present and
3. RESULTS AND DISCUSSION
3.1. Molecular Structure Description. Generally, differ-
ent fluorine substitutions only slightly influence bond lengths
between non-hydrogen atoms. The largest deviations are found
for the B−C, B−O, and C−F bonds. Geometrical parameters
and the corresponding plots are given in Table 1S in the
Supporting Information, whereas the molecular geometries are
illustrated in Figure 1. Nevertheless, while switching from the
unsubstituted to the tetrafluoro-substituted derivative, no
structural trend regarding B−O distances, reflecting a fluorine
atom influence, becomes obvious. In the case of the B−C bond,
its length slightly increases, when hydrogen atoms are replaced
by fluorine atoms, but again the correlation is not clear. Solely
the presence of four fluorine atoms at the phenyl ring gives a
significant B−C bond elongation, and, consequently, the B−O
bond shortening. It is, however, important to note that B−O
distances are in general much shorter (by about 0.03 Å) in a
crystal lattice than in the corresponding optimized isolated
molecules. This is obviously caused by the hydrogen bond
pattern formation (i.e., in general crystal field effects). Similarly,
in the case of the C−F distances, no visible trend is observed.
The X-ray-determined mF1 and 26dF1 diboronic acid struc-
tures exhibit the shortest C−F bonds (ca. 1.33 Å), which is,
however, caused by the presence of disorder. This is in contrast
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to the optimized crystal lattices, where the C−F distances are
comparable among all the studied derivatives (see Supporting
Information).
Table 1. Estimated Energy Values of Selected Intramolecular
Contacts (EI)
a
As indicated by the C2−C1−B1−O1 dihedral angle
(hereafter abbreviated as τ), the boronic groups in noFb0,
mF1, 26dF1, 25dF0, and tF0 are significantly rotated along the
carbon−boron bonds by about 18.8−37.6°. In the 23dF2 and
noFa4 structures they remain almost planar, regarding the
aromatic ring planes. High flexibility of the B(OH)2 group is
also characteristic for other structures of boronic acids and
their derivatives. The CSD search gives the whole spectrum
of τ angles, starting form planar conformations (τ = 0°) and
ending with perpendicular ones (τ = 90°) for ortho-sterically
hindered boronic acids (Figure 3S in the Supporting
Information). In order to support the discussion with the
energy landscape for para-diboronic acids, we have performed a
series of computations for three model compounds: phenyl-
boronic acid (phba) and its 2-fluoro (2Fphba) and 2,6-difluoro
(26dFphba) derivatives. The results of τ-constrained opti-
mization (the τ angle varies from 0° to 90° in steps of 5°,
performed at the MP218/aug-cc-pVTZ19 level of theory)
revealed that the planar conformation is the most stable one
(Figure 2). It is a well-known phenomenon that the rotation of
conformation
atom
X
syn
anti
contact
EI/kJ·mol−1
contact
EI/kJ·mol−1
H
F
C−H···O
C−F···O
−13
4
C−H···H−O
C−F···H−O
3
−3
a
Details are available from the Supporting Information.
intramolecular C−F···H−O interaction. This increases the stability
of planar conformation and increases the rotation barrier by ca.
7 kJ·mol−1. On the other hand, in the 26dFphba model molecule,
the repulsion between the fluorine atom and the oxygen atom
from the syn-conformed OH group facilitates the rotation. The
conjugation of boron atom with the aromatic ring amounts to
about 6 kJ·mol−1 and depends on the number of fluorine sub-
stituents. In the case of the derivatives richer in fluorine atoms, the
charge transfer from aromatic ring to the boron atom is less
pronounced. For example, for the tetrafluorinated phenylboronic
acid the conjugation energy is equal to ca. 4.5 kJ·mol−1.
The molecular flexibility features of the model 2Fphba and
26dFphba molecules can be directly related to the fluorinated
diboronic acids. The structures of 25dF0, 23dF2, and mF1
resemble 2Fphba, while tF0 and 26dF1 resemble 26dFphba.
Isolated molecule computation results show that the planar
conformation is the most stable one. However, at the lower
τ-angle range, the rotation energy requirement for the boronic
acid group is relatively small (rotation from τ = 0° to τ = 30°
requires 2 − 5 kJ·mol−1 for one boronic group). Therefore, in
the presence of crystal field, boronic groups deviate from the
planarity and the magnitude of such a deviation clearly depends
on the number and positions of fluorine substituents.
Figure 2. τ-Constrained optimization performed at the MP2/aug-cc-
pVTZ level of theory. Numerical values are deposited in Table 5S in
the Supporting Information.
Intramolecular contacts have also a visible influence on the
atomic angles around the boron atom. Because of the existence
of the C−H···O interaction, the C−B−O angles reach quite
small values of about 116°. In the presence of the repulsive
C−H···H−O contacts, they are larger than 120°. Similarly, the
C−F···H−O interaction formation leads to the increased
C−B−O angle (123−125°). Despite the repulsive nature of
the C−F···O interaction, the syn-conformed hydroxyl group gains
more flexibility and the angle is fairly close to 119°. The obtained
data are given in Table 1S in the Supporting Information, while
the geometrical deviations are summarized in Figure 2S.
the B(OH)2 group leads to a decreased charge transfer from the
aromatic ring to the boron atom. Apart from the conjugation
effects, the intramolecular contacts with the hydrogen or
fluorine atoms located in the ortho position(s) significantly
influence the relative molecular stabilization energy. It was then
possible to estimate the energy values of individual intra-
molecular contacts on the basis of the comparative com-
putations prepared for all model compounds with the B(OH)2
group in syn−syn, syn−anti, or anti−anti conformations (Table 1).
Contributions from the two hydroxyl groups, together with the
conjugation effect, sum up closely to rotation barriers of the
B(OH)2 group and indicate a relative conformational stability
of the compound. For instance, the weak intramolecular
C−H···O interactions between the oxygen atom from the syn-
conformed hydroxyl group and the ortho-positioned hydrogen
atom stabilize the planar conformation and therefore increase
the rotation barrier in phba. This effect is partially counter-
balanced by the repulsion between the hydrogen atom from the
second anti-conformed hydroxyl group and the hydrogen atom
from the ortho position at the aromatic ring. In 2Fphba, one of
the repulsive C−H···H−O contacts is replaced by the
3.2. Supramolecular Structures of noFb0, 25dF0 and
tF0. The 25dF0 and tF0 compounds crystallize in the triclinic
P1 and monoclinic P2 /n space groups, respectively. Molecules
̅
1
in both crystal structures are closely packed, with no solvent
content. We found that 25dF0 is structurally isomorphic to the
previously reported noFb0 (Figure 4). In the case of the tF0
compound, the residual density maps reveal hydrogen atom
disorder in the B(OH)2 fragments, whereas in the 25dF0
structure all atom positions are ordered (Figure 1S in the
Supporting Information). In the latter case the diboronic acid
moieties adopt a well-defined syn-anti conformation.
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Figure 3. (a) Molecular layers and their further aggregation in 25dF0 (b) and tF0 (c). Hirshfeld surfaces for the 25dF0 (d) and tF0 (e) molecules,
with a dnorm property mapped in the range from −0.75 to 1.20 (selected neighboring molecules and weak interactions are shown).
Similar to noFb0, the 25dF0 and tF0 molecules form hydrogen-
interactions as indicated by the flat red regions on the Hirshfeld
surface (Figure 3e). The above-mentioned F···B contacts are
also reflected in the 2D fingerprint plot as the increased
concentration of points located in the upper part of the two
characteristic spikes (Figure 4). Additionally, there are bright
red spots on the Hirshfeld surface near the C−F bond. It seems
that this corresponds to the interaction between the two
antiparallel C−F groups (the distance amounts to 2.955 Å).
However, the small C−F···F angle value (79.0°) suggests that
this is not a typical F···F interaction. This contact may also
result from the packing of molecules in the crystal lattice. In
contrast to the structures of noFb0 and 25dF0, the crystal
planes derived from the aromatic rings from the adjacent layers
bonded sheets parallel to the (011) and (100) crystal planes,
̅
respectively. Diboronic acid moieties are linked via centrosym-
metric R22(8) and R44(8) units within the two-dimensional (2D)
molecular motifs (Figure 3a). Nevertheless, 25dF0 and noFb0
exhibit quite a different picture of the supramolecular layered
assembly with respect to tF0. The molecules of both noFb0 and
25dF0 are held together by weak dimeric C(π)···B and O···B
interactions, which leads to the parallel orientation of the
molecules from adjacent layers (Figure 3b). These contacts are
very visible as bright red spots (i.e., close-range contacts) on
the corresponding Hirshfeld surface20 (Figure 3d). In turn, the
layered aggregation in the case of tF0 is based on the F···B
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Figure 4. Fingerprint plots of the Hirshfeld surfaces for each independent molecule in the structures of 1,4-phenylenediboronic acids (fingerprint
plots are based on the X-ray geometries; the most important intermolecular contacts are marked; more intense colors represent a more dense
accumulation of points).
Table 2. Cohesive Energy Values Calculated for the Molecules with the Geometry Taken from the Crystal Structures after All
a
opt
X‑ray
coh
X−H Bonds Set to Standardized Neutron Values (E ), and for the Optimized Geometries (E
)
coh
a
The calculations were carried out with the CRYSTAL and PIXEL programs.
in tF0, fitted by the least-squares method, are not parallel (Figure 3c).
The interplanar angle is equal to 70.6°. Furthermore, the C(π)···B
interactions, characteristic for noFb0 and 25dF0, were not
observed in the case of the tF0 structure.
Periodic computations carried out with the CRYSTAL and
PIXEL programs (Table 2) confirm the structural resemblance
of noFb0 and 25dF0. The cohesive energy value differs signi-
ficantly for tF0, being about 20 kJ·mol−1 lower than in the case
of noFb0 and 25dF0. Tetrafluorodiboronic acid is more
compact in packing, which is reflected in its overall more
advantageous stabilization energy. 25dF0 was found to be least
stabilized among compounds belonging to this group.
Two types of diboronic acid dimers characterized by the
lowest interaction energies can be distinguished in each of
the three analyzed structures (Table 3). These are hydrogen
bonded dimers creating molecular chains via boronic acid
groups (D1 − motif R22(8)), and boronic acid dimers
connecting two neighboring chains together (D2 − motif
R22(16)). The pattern is shown in Figure 3c, whereas the parti-
cular dimers are presented in Table 3. The distance between
aromatic ring centroids in D1 dimers is the same for 25dF0 and
tF0 (10.167 Å) and a little bit shorter for noFb0 (10.095 Å).
However, as indicated by the O···O distances (2.733 Å, 2.789 Å
and 2.735 Å for noFb0, 25dF0, and tF0, respectively), the
hydrogen bond length is the shortest in the case of tF0. Such a
shortening of hydrogen bonds in tF0 is counterbalanced by the
significant stretching of molecules along the Z direction.
Despite some differences in the geometries of hydrogen bonds,
the D1 dimer interaction energies seem to be quite alike among
these three compounds.
A different situation is observed for the D2 dimers, where the
O···O distance correlates with the torsion angle of the B(OH)2
group along the B−C bond. A significant value of τ in the case
of tF0 (30.5°) guarantees stronger hydrogen interactions within
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Table 3. Schematic Representations of Fluorinated Diboronic Acid Dimers Together with the Interaction Energies (ED)
Calculated with CRYSTAL at the DFT(B3LYP)/6-31G(d,p) Level of Theory and the Corresponding Geometrical Parameters
a
compound
dimer
ED/kJ·mol−1
interaction
dX···A (Å)
dD−X (Å)
dD···A (Å)
θD−X···A (°)
noFb0
D1
D2
D3
−47.3
−56.1
−15.5
O1−H1···O2#1
O2−H2···O1#2
C2···B1#3
1.733
1.825
3.762
3.510
1.789
2.003
3.562
3.295
1.735
1.841
3.445
2.930
1.668
1.690
1.691
3.406
3.213
3.132
3.525
3.424
3.226
3.178
3.516
1.752
3.388
3.225
3.401
3.228
0.987
0.980
2.719
2.734
176.8
152.7
C3A···B1#3
25dF0
tF0
D1
D2
D3
−49.6
−44.2
−18.5
O1−H1···O2#1
O2−H2···O1#2
C2···B1#3
0.984
0.975
2.770
2.858
174.6
145.3
C3···B1#3
D1
D2
D3′
−45.3
−68.1
−13.8
O1−H1A···O2#4
O2−H2A···O1#4
F1···B1#5
0.987
0.979
2.721
2.712
175.6
156.7
F2···B1#5
mF1
D1
D1
D1′
D3
−43.8
−43.1
−23.4
−26.3
O1−H1B···O1#6
O1−H1B···O1#6
O2−H2···O7#7
C5···B4#8
0.990
0.989
0.987
2.658
2.679
2.673
178.0
179.2
172.6
26dF1
23dF2
C6···B4#8
b
D3″
−25.0
F3···B2
F4···B2
b
C8···B1#8
C9···B1#8
b
F1···B3
F2···B3
b
noFa4
D1
D3
−43.4
−20.9
O2−H2···O1#9
C2···B1#10
C3···B1#10
C5···B2#10
C6···B2#10
0.983
2.726
170.2
a
b
d and θ denote distance and angle, respectively. Stands for intramolecular contact. Symmetry transformations: (#1) x + 1, y, z; (#2) −x, −y − 1,
−z + 1; (#3) x, y + 1, z; (#4) −x + 1, −y + 1, −z + 1; (#5) −x − 1.5, y + 0.5, −z − 0.5; (#6) x, y, −z + 1; (#7) x − 1, y, z + 1; (#8) x − 1, y, z;
(#9) −x+3, −y + 1, −z + 1; (#10) x − 1, y, z.
the D2 dimers (the O···O of 2.712 Å), and thus much more
efficient packing. For noFb0, the deviation of the B(OH)2
group from the aromatic ring planarity is less pronounced
(26.2°) and the O···O distance is equal to 2.734 Å, whereas for
25dF0 the C2−C1−B1−O1 torsion angle amounts to 20.4°
and the O···O distance to 2.858 Å. Both the angle and distance
values correlate perfectly with the D2 stabilization energy
magnitudes. In the case of tF0, the D2 dimer is the most, while
for 25dF0 the least stabilized one. It is also interesting to note
that in the structures of noFb0 and tF0, the D2 dimers were
found to be better stabilized than these of the D1 type.
As mentioned before, all three structures form well-defined
molecular layers via the discussed motifs (Figure 3b,c). There-
fore, in order to analyze the impact of dispersive interactions on
the crystal architecture stability, the interlayer stabilization energies
were evaluated. It comes out that the energy values are compar-
able between 25dF0 and tF0, being equal to −61.6 kJ·mol−1 and
−57.8 kJ·mol−1, respectively. They are though slightly less
beneficial in the case of noFb0 (−50.4 kJ·mol−1). Nevertheless,
the energetic results do not resemble the interlayer distance
sequence, which is 3.702 Å for noFb0, 3.787 Å for 25dF0, and
4.315 Å for tF0. Such an outcome is caused by a number of
competitive factors, that is, the character of the neighboring
layers, the presence of fluorine atoms influencing the atom net
charges, and then the interlayer distances. Even though the
interlayer distance is shortest in the case of noFb0, the layer
pattern is clearly less stabilized than in 25dF0. This is due to the
better stabilized D3 dimer type and the smaller B(OH)2 group
torsion angle value, which enables the intensified intermolecular
contacts. Furthermore, in the case of tF0, molecular layers, being
more distant, are differently mutually arranged than in noFb0
and 25dF0. Therefore, the interaction energy is less advanta-
geous than for 25dF0.
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Figure 5. Hydrogen-bonded chains of diboronic acids and their arrangement with the water molecules within mF1 and 26dF1 (only one occupied
site is presented for clarity) (a) 2D layers and (b) 3D catenated network.
Table 4. Interaction Energy Values (EW) for 26dF1 in
Contact with Water Molecules Estimated with CRYSTAL
at the DFT(B3LYP)/6-31G(d,p) Level of Theory Together
with Geometrical Parameters of Hydrogen Bond O−H···O
3.3. Supramolecular Structure of mF1 and 26dF1. The
mF1 and 26dF1 acids are isostructural and both crystallize as
monohydrates in the orthorhombic Cccm space group. As a
consequence of the statistical disorder, the molecules occupy a
special position at the inversion center and a mirror plane. The
refinement shows that each of the four sites is occupied by
0.25:0.75 and 0.5:0.5 ratio of fluorine to hydrogen atoms for
the structures of mF1 and 26dF1, respectively. Similarly, the
hydrogen atoms belonging to the B(OH)2 groups and water
molecules can occupy two sites. Because of the presence of the
disorder, and because of the fact that in the asymmetric part of
the unit cell there is a half of the molecule, detailed analysis
of the intermolecular interaction patterns using the standard
Hirshfeld surface methods and CRYSTAL computations is
hampered. Therefore, for the purpose of the further analysis, we
have lowered the symmetry of the system from the Cccm space
group to the P21/n one (metric properties were unchanged),
preserving geometrical parameters and removing the disorder.
The presence of the disorder allows a few combinations of the
fluorine derivative mutual arrangement in the crystal lattice.
However, computational study of these different possibilities
revealed that there is almost no energy difference among them
(Table 6S in the Supporting Information). Consequently, to
simplify the problem, we chose a certain molecular arrangement
for mF1 and 26dF1 to remove the disorder, as illustrated in
Figure 5a.
According to expectations, every molecule of diboronic acid
interacts with its two neighbors in the centrosymmetric R22(8)
synthon, leading to a hydrogen-bonded chain formation along
the Z direction (Figure 5a, motif R22(8)). The O···O distance
for mF1 compound is equal to 2.658 Å (Table 3), while for
26dF1 it is a little bit longer and amounts to 2.679 Å. The D1
dimer energies are comparable in both cases. Water molecules
built into the crystal lattice act as two donors and two acceptors
of hydrogen bonds formed with the boronic groups. There-
fore, they link four neighboring diboronic chains into a three-
dimensional (3D) catenated network (Figure 5a, motif
R66(12)). Water molecules, being less acidic than diboronic
acid species, interact more efficiently as boronic acid proton
acceptors rather than donors. This is a consequence of the
weakened basicity of the oxygen atoms belonging to the
boronic fragment, donating electrons toward the p orbitals of
the boron atom. The interaction energy values, between the
water and the boronic acid, obtained for the optimized
structures are shown in Table 4.
a
Interactions (Optimal Geometry)
motif EW/kJ·mol−1 dO···H (Å) dH···O (Å) dO···O (Å) θO−H···O (°)
W1
W2
W3
W4
−17.7
−28.1
−35.7
−19.7
0.984
0.989
0.989
0.984
1.735
1.710
1.724
1.747
2.706
2.693
2.702
2.719
168.4
171.9
169.3
168.9
a
Schematic representation is given above the table.
represents the regions on the Hirshfeld surface corresponding
to the noninteractive fluorine and hydrogen atoms contacts. In
general, the Hirshfeld surface plot of the 26dF1 structure is very
similar to that of mF1. There are only some small discrepancies
noticeable in the related fingerprint plots. The relatively sparse
distribution of points visible on the 26dF1 fingerprint plot,
in-between the pair of the O···H spikes, corresponds to the
close H···H distances across boronic acid cyclic dimers. Similar
observation was reported for carboxylic acids.20c,d However,
quite surprisingly, those features mostly disappear when the
structure is optimized (Figure 5S in Supporting Information).
This may suggest that in this case this is rather an artifact of the
IAM model employed in the structure refinement. It should be
noted that the investigation does not support the formation of
any significant weak interactions involving fluorine and boron
atoms. In addition, the volume of the 26dF1 unit cell is larger
by about 20 Å3, than for the mF1, which suggests a less efficient
packing in the former case.
CRYSTAL computations confirm the comparable stability
of both isomorphic forms (−273 kJ·mol−1 for mF1 and
−267 kJ·mol−1 for 26dF1). The mF1 structure seems to be
slightly more advantageous than 26dF1. This might result from
its less compact packing which was mentioned before. Longer
intermolecular distances are probably caused by the fluorine
atoms. The fluorine atoms desire more space than hydrogen
The fingerprint plots of the mF1 and 26dF1 molecules show
a singular feature near the (di = 2.4 Å, de = 2.0 Å) point. This
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Figure 6. (a) Molecular chain constructed by the 23dF2 diboronic acid and water molecules. (b) Packing diagram showing how the weak C(π)···B,
F···B, and O···B interactions (marked as dashed lines) participate in the formation of the 2D layers. (c) Hirshfeld surface for the 23dF2A molecule
depicted with some weak interactions.
atoms and also influence the molecular charge distribution.
This, in turn, affects the geometry and molecular assembly. The
26dF1, which contains two fluorine substituents in a diboronic
acid molecule, is thus less tightly surrounded by other moieties
in its crystal lattice. On the other hand, it seems that longer
interatomic contacts do not hamper the interaction strength
between acid molecule dimers building the crystal network.
Indeed, despite the example of the D1 dimer, the cohesive
energies evaluated for the waterless mF1 and 26dF1 hypo-
thetical forms (i.e., the same geometry and structural
parameters but with solvent moieties excluded) are also very
much alike (about 112 kJ·mol−1). This suggests that there is a
balance between the fluorine atom effect and diboronic acid
intermolecular distance, leading to the similar stabilization
strength. The overall cohesive energy difference must then
come from a subtle dissimilarity in the interactions with the
solvent species. Less compact diboronic acid arrangement in
the 26dF1 structure may preserve the interactions in the
diboronic acid net. However, due to the longer intermolecular
distances this may lead to less efficient interactions with water
moieties, affecting the cohesive energy value.
As a supplementation of the whole structural discussion
concerning the two isomorphic compounds, a CSD search was
carried out, leading to an interesting finding. It appears that the
supramolecular patterns described for the structures of mF1 and
26dF1 are very similar to those found for a pseudopolymorphic
form of 4-carboxyphenylboronic acid.21 Fairly similar unit cell
parameters and 3D arrangements, in which water molecules
span hydrogen-bonded chains, make the three structures
identical from the topological point of view. The only difference
is the internal symmetry of the crystal. While the structures of
mF1 and 26dF1 crystallize in the centrosymmetric Cccm space
group, the carboxylic acid adopts a non-centrosymmetric Ccc2
one. This is mainly because the adjacent molecules are held by
hydrogen bonds formed between boronic and carboxylic
groups; therefore there is no center of symmetry. Clearly, an
addition of the inversion center into the Ccc2 space group
transforms it directly into Cccm. However, it is worth noting
that due to low data quality it is hardly possible to judge if the
apparent Ccc2 space group symmetry is the right one. The
improper assignment of hydrogen atoms, a possible disorder of
the whole acid moiety, and the high temperature of the measure-
ment cause serious doubts concerning the structure reliability
and may rather indicate the higher Cccm symmetry of the
crystal lattice. This suggestion, in fact, is supported by the
CHECKCIF report. Unfortunately it was impossible to verify
these suppositions in the absence of the structure factor data.
3.4. Supramolecular Structure of 23dF2. The 23dF2
constitutes another fluorine diboronic acid derivative charac-
terized by the increased water content in its crystal lattice.
The asymmetric part of the unit cell contains two molecules
of diboronic acid (23dF2A and 23dF2B) and four water
molecules. No disorder is observed within the B(OH)2 moiety
and fluorine atoms. Both boronic groups in the first molecule
(bound to C1 and C7 carbon atoms) adopt a syn−syn con-
formation. In the second molecule the syn−anti conformations
are observed (for the B(OH)2 groups bound to C4 and C10
centers). The supramolecular structure of 23dF2 is the most
distinct one from all other structures described so far in this
manuscript. Because of the presence of numerous inter-
molecular hydrogen bond interactions, supramolecular assem-
bly is based on a quite complex pattern of hydrogen-bonded
network. In contrast to the remaining diboronic acids, mole-
cular chains in 23dF2 are not held by typical centrosymmetric
R22(8) dimers. Instead, molecules of diboronic acid are mutually
displaced and form chains (along the [101] crystal direction),
̅
in which water molecules constitute a kind of a molecular glue
(Figure 6a). Within the chains, the molecules of 23dF2A
and 23dF2B are in the interspersed arrangement and interact
one with another via single hydrogen bonds only (dimer D1′).
The second boronic hydroxyl group is engaged in hydrogen
interaction with water molecules, two of which (O9 and O11)
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act as single donors and single acceptors, whereas the O10 and
O12 ones are double acceptors of hydrogen bonds. Similarly
skewed architectures of diboronic chains are rare and have
been solely observed for the structure of bis(4-boronicphenyl)-
acetylene.2h The chains associate further by the interactions
between the B(OH)2 groups and water molecules, supported
by the water−water contacts. In summary, each of the four
symmetrically independent water molecules is engaged in three
O−H···O interactions with the boronic fragments, linking dibo-
ronic acids within and in-between chains, and also participates
in one interaction with another water molecule.
unit. This makes −324 kJ·mol−1 on average per one diboronic
acid molecule and two water molecules, and is about
70 kJ·mol−1 lower than the corresponding values for mF1 and
26dF1 (Table 2). Such an energy difference, with respect to the
mF1 and 26dF1 crystal structures, results from the presence of
the additional water molecule, being an extra hydrogen bonding
donor and acceptor. On the other hand, the anhydrous struc-
ture stabilization energy of 23dF2 is substantially less profitable
than in the case of mF1 and 26dF1 (−91.1 kJ·mol−1 and about
−112 kJ·mol−1, respectively). This is because diboronic acid
molecules are less compactly arranged in the crystal lattice of
23dF2 as some space is dedicated for water molecules.
Therefore, the distance between chains is greater and boronic
acid groups adopt more stable, as indicated by single point
calculations (Figure 2), almost flat conformation, lying in the
aromatic ring plane. Such an arrangement of the acid species
reduces their mutual interaction. However, the π-stacking
contacts between the two neighboring molecular layers are
more efficient, when compared to the corresponding
interactions observed for the other studied systems (Table 3,
dimers D3 and D3′).
The Hirshfeld surfaces for both symmetry-independent
molecules of 23dF2 have very similar shape and interaction pat-
terns. Eight substantial hotspots belong to the strong O−H···O
interactions, and they are represented as a symmetric pair
of spikes in the fingerprint plots. The hydrogen-bonded
framework is reinforced by much weaker, dispersive interactions.
Strong Lewis acidity of boron atom in its three-coordinated
state attracts more electronegative partners such as oxygen and
fluorine atoms but also the π-densities. Several bright red spots
located at the both sides of the Hirshfeld surface are clearly
visible. These arise from the C(π)···B and O···B interactions
and contribute to the relatively dense distribution of points on
fingerprint plots. The other important spot related to the boron
atom is recognized as the F···B interaction and is located near
the (de = 1.7 Å, di = 1.5 Å) point in the adequate fingerprint
plot. The molecules of 23dF2A and 23dF2B belonging to
parallel chains are paired due to the self-complementary of
C(π)···B (dC6···B4 = 3.209 Å, dC9···B1 = 3.219 Å) and F···B inter-
actions (dF3···B2 = 3.127 Å, dF2···B3 = 3.195 Å). As a result of
these weak contacts the 23dF2 molecules form D3 dimers,
similar to the ones observed for the noFb0 and 25dF0
structures. However, unlike in 23dF2, the weak C(π)···B
interactions in noFb0 and 25dF0 arise symmetrically from both
sides of the molecule, while in the case of 23dF2 one side is
arranged in C(π)···B contacts and the other in F···B contacts
(Figure 6c). There is also a quite intensive spot visible on the
Hirshfeld surface, which corresponds to a very short H···H
distance of 2.270(2) Å between aromatic hydrogen atoms of
23dF2A. This contact is represented by a sharp spike along the
diagonal at de = di = 1.1 Å. It is notable that for the second
molecule from the asymmetric unit, 23dF2B, the corresponding
spike is much shorter and bulged, which indicates a longer
H···H distance.
All the strong O−H···O and weak C(π)···B, F···B, and O···B
interactions have a great contribution to the supramolecular
structure stabilization. The association of hydrogen-bonded
chains by weak interactions involving boron atom, within the
D3 dimers, and lateral hydrogen contacts from dimeric water
units, leads to the formation of molecular layer (propagating
parallel the (010) crystal plane) as it is shown in Figure 6b. The
3D structure has a double-layered herringbone architecture
with the interlayer distance equal to 7.053 Å and the bond
angle between the mean square planes of nonparallel molecules
from adjacent layers equal to 28.96°. We suppose that the role
of water in this structure, as well as in the other structures of
diboronic acids, goes beyond the hydrogen-bonded architecture
building unit. In accordance with theoretical calculations, water
molecules allow for optimizing the interactions between
electronegative atoms or aromatic π-electrons and boron atom.
The complexity and effectiveness of molecular packing of
23dF2 in the crystal lattice is reflected in the low cohesive
energy value, which amounts to −648 kJ·mol−1 per asymmetric
The cohesive energy computation results show the vast impact
of water molecules on the overall crystal lattice stabilization.
The energetic gain due to the presence of solvent species
amounts to over 450 kJ·mol−1 per asymmetric unit (i.e., the
difference between the cohesive energy derived for the studied
crystal and its waterless analogue). The solvent effect on crystal
structure stabilization energy is illustrated by the example of
D1′ dimer and T4 arrangement (Figure 6a), which is composed
by two diboronic acids and two water molecules. The contri-
bution from water molecules to the T4 stabilization energy
reaches about 115 kJ·mol−1, which shows the scale of the
solvent effect. Similar to the other examined structures con-
taining water molecules, the strength of the hydrogen bond
between boronic acid and water molecule is greater when that
water molecule constitutes a boronic acid proton acceptor.
3.5. Supramolecular Structure of noFa4. This particular
structure was reported by Hopfl et al.2l Therefore, here we just
̈
give a brief description of its supramolecular architecture and
analyze the patterns of intermolecular interactions in order to
provide a comprehensive picture supplementing our study. The
noFa compound crystallizes in the triclinic P1 space group
̅
4
with four molecules of water per one molecule of diboronic
acid, which constitutes the highest water content in the crystal
lattice among the examined systems.
As observed in the other studied systems, except for 23dF2,
the main pattern in the crystal lattice of noFa4 is the one-
dimensional (1D) molecular chain constructed by the centro-
symmetric R22(8) motifs involving the B(OH)2 groups (D1
dimer). These associate further by weak C(π)···B and O···B
interactions (D3 motif) forming a molecular layer parallel to
the (113) crystal plane (Figure 7b). Weak interactions are well
̅
visible as bright spots on the Hirshfeld surface (Figure 7a). The
molecular arrangement is similar to the ones found in noFb0,
25dF0, and 23dF2. However, in the case of noFb0 and 25dF0
boronic groups are significantly rotated with respect to the
aromatic ring planes, which leads to the formation of the
undulated 2D molecular layers of diboronic acid chains joined
via side hydrogen bonds. In the case of noFa4, the chain motifs
are connected with the water mediated hydrogen bonding,
increasing the dimensionality of the system. Consequently,
noFa4 exhibits a 3D structure formed by the layers of diboronic
acids intercalated by the layers of water molecules (Figure 7b).
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Figure 7. (a) Hirshfeld surface obtained for the noFa4 structure shown with selected neighboring molecules and weak interactions. (b) Packing
diagram showing selected adjacent layers (blue and yellow arrows show the layer propagation) of diboronic acid and water molecules.
Such arrangement allows molecules of diboronic acid for
adopting a more stable, flat conformation.
In the noFa4 structure, it was also possible to compute the
interlayer interaction energies between slabs containing water
molecules. As illustrated in Figure 7b, there are well visible
molecular layers parallel to the (010) crystal planes. Computa-
tional result for the stabilization energy of such diboronic acid−
water slabs showed once again the importance of the solvent
content. This interaction reaches −187.8 kJ·mol−1 per a unit
cell and reflects the interaction strength between diboronic acid
and water species.
Computational studies show that, as it was in the case of
23dF2, the waterless structure of noFa4 is characterized by the
cohesive energy greater than that obtained for other systems
containing lower amounts of water in their structures. This is
due to a more dispersed crystal packing of noFa4. Although
there is much more space between the neighboring chain
motifs lying in the same plane parallel to the (113) crystal
̅
plane, so as to accommodate the water species, the distance
between parallel dispersively interacting chains is smaller than
the corresponding values for noFb0 and 25dF0, and amounts to
3.284 Å. Consequently, the interaction between 2D layers is
equal to −89.9 kJ·mol−1 and is lower than that for noFb0 and
25dF0. The stabilization energy of D1 motif is comparable to
the results obtained for the same structural motif observed in
the other studied systems. The D3 dimer, in turn, seems to be
slightly better stabilized than in the other cases, except for
23dF2. The D3 dimer interaction energy results for 23dF2 and
noFa4 suggest that the π-stacking contacts are more efficient
when boronic groups lie in the aromatic ring planes as then the
interacting molecules may adopt closer arrangement in space
which provides a better π-covering. It also seems that the
presence of fluorine atoms usually increase the strength of such
interactions.
The total cohesive energy per asymmetric unit amounts to
−420.4 kJ·mol−1 for the noFa4 crystal structure. The same
quantity for its waterless analogue equals −91.0 kJ·mol−1. This
means that the total energy gain due to the presence of water
molecules is of about 329 kJ·mol−1 in magnitude. The
stabilization energy of diboronic acid interacting with four
surrounding water molecules is also significant (−98 kJ·mol−1).
It is worth stressing here that in general each additional water
molecule lowers the crystal cohesive energy with a smaller
impact. One water molecule in mF1 and 26dF1 increases the
crystal stability of over 150 kJ·mol−1 with respect to the
nonsolvent case. In turn, in the case of 23dF2, two water
molecules lower the cohesive energy of 250 kJ·mol−1 on
average, which means that about 125 kJ·mol−1 per a solvent
moiety. Finally for noFa4 the impact of each water molecule is
reduced to about 80 kJ·mol−1.
4. COMPARATIVE REFLECTION AND CONCLUSIONS
The studied series of diboronic acid derivatives constitutes
a structural continuum of differently hydrated architectures.
However, at the same time, it might be considered as a
sequence of diboronic acid modifications gradually enriched in
the fluorine content. Therefore, particular attention should be
paid to these two leading aspects, that is, water incorporated in
the crystal lattice and fluorine substituents, and their influence
on the spatial arrangement of molecules in the resulting crystal
networks.
Together with the growing number of water molecules per
acid moiety, we observe the stepwise alternation of the crystal
packing, starting from the layered aggregation in noFb0, 25dF0,
and tF0, through the catenated network in isostructures mF1
and 26dF1, ending with the double-herringbone packing and
alternate layers of diboronic acid and water molecules for
23dF2 and noFa4, respectively. As indicated by the theoretical
calculations performed in the CRYSTAL and PIXEL programs,
the general trend is that diboronic acid structures containing a
greater amount of water are better stabilized (Table 2). Indeed,
in all of the studied crystal structures the main structural motifs
are based on hydrogen bonds, and the presence of water mole-
cules provides the increased number of this kind of inter-
molecular contact. This is reflected in the augmented contri-
bution of the electrostatic and polarization components to the
total crystal lattice stabilization energy. PIXEL results revealed
that in the case of noF, 25dF0, and tF0 the polarization energy
component is less significant than the dispersive energy con-
tribution, while the electrostatic energy value is the most
substantial one. In turn, in the case of mF1 and 26dF1 the
polarization energy component strongly outnumbers the
dispersive energy value. These two are also characterized by
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much more stabilizing electrostatic interactions than noFb0,
25dF0, and tF0 (over 160 kJ·mol−1 more advantageous).
The percentage contributions of hydrogen bond contacts to
the overall stabilization energy ranges from about 60% for the
anhydrous group and mF1 and 26dF1, through 65% for 23dF2,
to nearly 75% for noFa4. The average strength of hydrogen
bonding amounts to 24−28 kJ·mol−1. This indicates that
hydrogen bonds are slightly stronger when water−water
contacts are enabled.
The most important synthons formed via hydrogen bonding
contacts are R22(8) and R22(16), which correspond to the D1
and D2 dimers. The average strengths of D1 and D2 dimer
interactions are about −40 to −50 kJ·mol−1. These energy
values are comparable to the binding energies of other boronic
acid dimers reported in the literature (−50.2 kJ·mol−1 for the
HB(OH)2 dimer22 and −50.5 kJ·mol−1 for the NH2−CH2−
B(OH)2 dimer23 both calculated at the MP2/6-311G(d,p) level
of theory, and −49.4 kJ·mol−1 for phenylboronic acid dimer2c at
MP2/6-31G(d,p)). The D1 dimer is formed in each structure,
except for 23dF2. In the latter case we observe dimers
consisting of mutually shifted diboronic acids (D1′), where the
interaction between two acid molecules is weaker. The D1′
motif is then additionally stabilized from the sides with the aid
of water molecules. In turn, the D2 motif is characteristic for
the anhydrous structures, where hydrogen bonded chains are
linked together from the sides via hydrogen bonding created
between the acid molecules. In the water-containing structures,
the space around diboronic acid chain motifs is filled with
different water arrangements.
compounds. In the case of the mF1 and 26dF1 monohydrates, a
high value of the τ angle enables optimal contacts with water
molecules. In the structures with a higher water content
(23dF2, noFa4), the molecules of diboronic acids are no longer
arranged in the side contact patterns. Therefore, there is much
more space around chain motifs, which enables acid groups to
adopt a more energetically stable planar conformation (with
respect to aromatic rings). It is worth noting here that this flat
conformation allows for a stronger π-stacking interactions
observed for the D3 type dimer. Additionally, in the case of the
23dF2 and noFa4 structures, water molecules can interact one
with another. This, in turn, supports formation of the effec-
tive weak interaction network, where more than one water
molecule per one acid moiety is present.
Having a closer look at the proton disorder within boronic
group, it seems that it is also ruled by intramolecular
interactions with fluorine atoms. In the 25dF0 structure, the
position of the fluorine atoms is well-defined as a result of the
complementary C−H···O and C−F···H−O intramolecular
contacts. This is also true for the 23dF2 derivative, where the
positions of the hydrogen atoms are determined by directional
interactions with the water molecules. For the more symmetric
tF0 derivative, the intramolecular interactions are weaker.
Moreover, there is no side preference (i.e., two fluorine atoms
are always in ortho positions). In the case of mF1 and 26dF1
derivatives, the fluorine atoms are systematically disordered
(Figure 8). However, without multitemperature neutron or
The second aspect concerns the fluorine substitution of the
aromatic ring and its influence on the diboronic acid binding
properties. As shown by Hirshfeld surface analysis and the
theoretical calculations, the C−H···F and F···F contacts do not
directly participate in the composition of the crystal lattice. This
is especially noticeable in the structures of mF1 and 26dF1,
where the network is dominated by strong hydrogen
interactions and does not include any significant weak
interactions involving fluorine atoms. This is supported by
the fact that the fluorine atoms are disordered and can occupy
each site at the aromatic ring with equal probability. It is also
important to note that the additional fluorine atom does not
affect the stabilization of the D1 hydrogen-bonded dimers
significantly. The direct contacts involving fluorine atoms are
also absent in the structure of 25dF0, which is isostructural to
noFb0. Furthermore, only in the case of 23dF2 and tF0 (D3′
and D3″ dimer, respectively) direct interactions employing the
fluorine atoms (F···B contacts) are observed.
As mentioned before, a significant twisting of the B(OH)2
group in noFb0, 25dF0, and tF0 leads to more efficient contacts
between adjacent acid molecules and thus to more compact
packing. The more advantageous values of the D2 dimer
interaction energies in tF0 and noFb0 are partially counter-
balanced by the less stable molecular conformation (boronic
groups are more twisted). The lower stability of the boronic
acid conformation is caused by weaker conjugation of the
twisted boronic group with the aromatic ring, and also by
weaker intramolecular hydrogen O−H···F or/and C−H···O
contacts. In contrast, two intramolecular O−H···F and two
C−H···O contact types present in 25dF0 hamper the rotation
of the boronic group and stabilize the flat conformation.
Consequently, this molecule is to a less extent distorted from
planarity, and thus the D2 dimer is less efficiently stabilized. A
substantially different effect is found for the other studied
Figure 8. Residual density map for the D1 dimer moiety in 26dF1
(reconstructed without hydrogen atoms on OH groups). Proton
disorder is clearly visible.
X-ray high-resolution data, we cannot justify whether the
observed proton disorder is static or dynamical in nature, and
how it is governed by the intramolecular interactions. More
detailed studies on that matter for similar dimers have been
performed recently for carboxylic acids.24
In conclusion, the above results suggest that the C−H···F
and F···F contacts are being avoided. In other words, they do
not participate directly in the formation of a crystal lattice.
Nevertheless, the packing motifs discussed here indicate some
trends in the formation of the F···B interactions, which
contributes to the specific understanding of the influence of
fluorine interactions, particularly in the presence of boron
atoms. Moreover, the role of a fluorine atom goes beyond the
directional impact on the structural stabilization. The geometry
change resulting from the fluorine substitution is reflected, for
example, in the D2 dimer stabilization energies, or in the
strength and character of boronic acid contacts with water
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δ = 28 ppm. 19F NMR ([D6]DMSO, 376.47 MHz): δ = −133.5 ppm.
C6H4B2F4O4 (237.71): calculated: C (30.32), H (1.70); found:
C (30.43), H (1.59).
molecules. Fluorine atoms affect the torsion angle of a boronic
group by stabilizing/destabilizing contacts between an OH
group and hydrogen/fluorine atoms. Additionally, our work
shows and, to some extent explains, the substantial role of the
solvent molecules incorporated into a crystal lattice.
5.2. Crystallization. Single crystals of the studied compounds and
their hydrates were prepared by crystallization of the compounds from
an appropriate solvent. The crystals of tF0 and 25dF0 were obtained as
pure forms upon crystallization from 2:1 toluene/acetone solution.
The crystals of hydrates mF1 and 26dF1 were obtained by slow
evaporation of appropriate acetone solutions, while the crystallization
from 1:1 acetone/water solution gives single crystals of 23dF2.
Nevertheless, applying different crystallization conditions (various sol-
vents, evaporation surfaces, etc.), we did not manage neither to obtain
pure forms of mF, 26dF, and 23dF, nor hydrates of 25dF and tF.
5.3. Crystal Structure Determination. X-ray diffraction data sets
for single crystals of mF1, 25dF0, tF0 were collected at 100 K on a
Bruker AXS Kappa APEX II Ultra diffractometer with a TXS rotating
anode (Mo−Kα radiation, λ = 0.71073 Å), multilayer optics and
equipped with an Oxford Cryosystems nitrogen gas-flow attachment.
The data collection strategy was optimized and monitored using the
appropriate algorithms applied in the APEX2 program package.25 Data
reduction and analysis were carried out with the APEX2 suit of
programs (integration was done with SAINT26). The multiscan
absorption correction, scaling, and merging of reflection data were
done with SORTAV.27 Single crystals of 26dF1 and 23dF2 were
measured on a Kuma KM4CCD κ-axis diffractometer with graphite-
monochromated Mo−Kα radiation and equipped with an Oxford
Cryosystems nitrogen gas-flow apparatus. Data reduction and analysis
were carried out with the Oxford Diffraction Ltd. suite of programs.28
All structures were solved by direct methods using SHELXS-97 and
refined using SHELXL-97.29 Selected crystal data for all crystals are
summarized in Table 5. In the case of mF1 and 26dF1 it was necessary
to include a disorder model with fluorine and aromatic hydrogen
atoms. The site occupancy factors of fluorine atoms were fixed at the
exact values of 0.25 and 0.50 for mF1 and 26dF1, respectively. Other
details are available from the Supporting Information.
5. EXPERIMENTAL SECTION
5.1. Materials and Synthesis. All reactions were carried out
under an argon atmosphere. Solvents were stored over sodium wire
before being used. n-Butyllithium (10 M solution in hexanes), diiso-
propyamine, and triizopropyl borates were used as received without
further purification. 1H and 13C NMR chemical shifts are given relative
to TMS using residual solvent resonances. 11B and 19F NMR chemical
shifts are given relative to BF3·Et2O and CFCl3.
Fluoro-1,4-phenylenediboronic Acid (mF). A solution of nBuLi
(10 M, 2.0 mL, 20 mmol) was added to the stirred solution of
1,4-dibromo-2-fluorobenzene (5.10 g, 20 mmol) in Et2O (20 mL) at
−80 °C. After ca. 30 min a mixture containing the lithium derivative
was quenched with B(OiPr)3 (4.61 mL, 20 mmol). The mixture
became thick, and therefore, it was diluted with an additional
20 mL of THF. The mixture was allowed to warm to −60 °C and then,
after another 30 min of stirring at this temperature, the solution of
nBuLi (10 M, 2.0 mL, 20 mmol) was added, followed by the addition
of a second portion of B(OiPr)3 (4.84 mL, 21 mmol). After ca. 1 h of
stirring at −60 °C the mixture was warmed to −30 °C and quenched
with 2 M ethereal solution of HCl (21 mL). The mixture became clear.
At 20 °C water was added, white precipitate appeared and it was
filtered. Resulting powder was washed with Et2O and water and dried
to give the title compound. Yield, y = 2.70 g (72%); melting point
1
temperature, Tm > 350 °C. H NMR ([D6]acetone, 400 MHz): δ =
7.71 (t, J = 7.2 Hz, 1 H, Ph), 7.39 (d, 1 H, Ph), 7.39 (s, 2 H, B(OH)2),
7.21 (d, J = 2.4 Hz, 2 H, B(OH)2), 3.09 (s, 2 H, H2O) ppm. 13C{1H}
NMR ([D6]acetone, 100.6 MHz): δ = 167.5 (d, J = 243.9), 136.6
(d, J = 7.6 Hz), 130.1 (d, J = 2.2 Hz), 120.4 (d, J = 22.8 Hz). 11B NMR
([D6]acetone, 64.16 MHz): δ = 28 ppm. C6H7B2FO4·H2O (201.75):
calculated: C (39.22), H (3.84); found: C (39.13), H (3.92).
5.4. Computational Methods. (a). Single-Point Calculation
with GAUSSIAN.30 The single-point calculations were performed
within the second-order Møller−Plesset (MP2) approximation.18 Dunning−
Woon aug-cc-pVTZ,19 basis sets were used throughout. The single-
molecule constrained energy scan of C2−C1−B1−O1 dihedral angle
was also performed at the MP2/aug-cc-pVTZ level of theory. During
the scan procedure only the dihedral angle C2−C1−B1−O1 was
constrained and all other parameters were fully optimized. During the
calculations no symmetry constraints were applied.
2,5-Difluoro-1,4-phenylenediboronic Acid (25dF). Compound was
prepared as described for mF, starting with 1,4-dibromo-2,5-difluoro-
benzene, except that the first step of the reaction was accomplished
with an in situ technique (to the solution of substrate and B(OiPr)3
2M nBuLi was added). Moreover, THF instead of Et2O was used as
solvent, and all lithiation/boronation steps were performed at −90 °C.
The resultant mixture was hydrolyzed with 1.5 M aqueous H2SO4
(15 mL) at −10 °C. The water phase was separated and followed by
extraction with diethyl ether (2 × 15 mL). The extracts were added to
the organic phase, which was concentrated under reduced pressure.
A solid residue was filtered and washed consecutively with water
(2 × 10 mL) and hexane (5 mL). Drying in vacuo afforded the title
compound as a white powder. Tm = 214 − 215 °C. 1H NMR
([D6]DMSO, 400 MHz): δ = 8.34 (s, 4 H, B(OH)2), 7.16 (t, J =
6.4 Hz, 2 H, Ph) ppm. 13C{1H} NMR ([D6]DMSO, 100.6 MHz): δ =
169.2 (d, J = 23.2 Hz), 130.1 (dd, J = 247.27 Hz, J = 11.4 Hz).
11B NMR ([D6]DMSO, 64.16 MHz): δ = 28 ppm. C6H6B2F2O4
(201.73): calculated C (35.72), H (3.00); found: C (35.66), H (2.94).
Tetrafluoro-1,4-phenylenediboronic Acid (tF). A solution of
lithium diisopropylamide (LDA) freshly prepared from diisopropyl-
amine (10.10 g, 100 mmol) and nBuLi (10 M, 10.0 mL, 100 mmol)
was added to a stirred solution of 1,2,4,5-tetrafluorobenzene (7.5 g,
50 mmol) containing B(OiPr)3 (14.6 g, 100 mmol) in THF (70 mL)
at −80 °C. White slurry was formed. After about 30 min the mixture
was allowed to warm to −30 °C. Then it was quenched with 2 M
ethereal solution of HCl (50 mL), warmed to room temperature, and
2 M aq. solution of HCl was added. The water phase was separated
followed by extraction with ether (2 × 15 mL). The extracts were
added to the organic phase, which was concentrated under reduced
pressure. Drying in vacuo afforded the title compound as a white
powder, Tm = 184 − 186 °C. 1H NMR ([D6]DMSO, 400 MHz): δ =
8.08 (s, 4 H, B(OH)2) ppm. 13C{1H} NMR ([D6]DMSO, 100.6
MHz): δ = 147.5 (d, J = 233.5). 11B NMR ([D6]DMSO, 64.16 MHz):
(b). CRYSTAL Calculations. All energy computations within the
CRYSTAL09 program package15 were performed at the DFT-
(B3LYP)31 level of theory. 6-31G(d,p)32 molecular all-electron basis
set occurred to be sufficient for the purpose of the conducted
calculations. Both Grimme dispersion correction33 and correction for
the basis set superposition error were applied. Ghost atoms were
selected up to 5 Å distance from the studied molecule in a crystal
lattice and were used for the basis set superposition error estimation.
The evaluation of Coulomb and exchange series was controlled by five
thresholds, set arbitrary to values of 10−7, 10−7, 10−7, 10−7, 10−25. The
condition for the SCF convergence was set to 10−7 on the energy
difference between two subsequent cycles. Shrinking factor was equal
to 4, which refers to 30−36 k-points (depending on space group
symmetry) in the irreducible Brillouin zone in the case of the studied
systems and assures the full convergence of the total energy. Two
types of coordinates were used. First, molecular geometries were taken
directly from the X-ray structural data analysis, while all X−H bonds
were fixed at standard neutron distances. Then, all the structures were
optimized with CRYSTAL and they served for the subsequent energy
calculations. In the case of the structures, which exhibit layer architectures,
the same two sets of coordinates were subjected to crystal interlayer
interaction computations. The majority of the calculation parameters were
set identical as for the purpose of the cohesive energy determination. The
only difference was in ghost atom definitions. Here, an additional upper
and lower molecular layers were used as ghost functions for appointing
the basis set superposition error.
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Table 5. Selected Crystal Data, Data Collection and Refinement Parameters for Measured 1,4-Phenylenediboronic Acids
mF1
26dF1
23dF2
25dF0
tF0
formula
C6H7B2FO4·H2O
201.75
C4H8B2F2O·H2O
219.74
C6H6B2F2O4·2H20
237.76
C6H6B2F2O4
201.73
C6H4B2F4O4
237.71
molecular mass, Mr (a.u.)
temperature, T (K)
crystal system
space group
a (Å)
100(1)
100(1)
100(1)
100(1)
100(1)
orthorhombic
Cccm
orthorhombic
Cccm
monoclinic
P21/c
triclinic
monoclinic
P21/n
P1
̅
12.049(1)
7.277(1)
10.055(1)
90
12.207(2)
7.329(1)
10.081(2)
90
9.551(1)
28.212(2)
7.652(1)
90
4.984(2)
5.257(2)
7.423(3)
74.67(1)
84.64(1)
89.00(1)
186.7(1)
1
8.426(1)
5.024(1)
10.166(1)
90
b (Å)
c (Å)
α (°)
β (°)
γ (°)
volume, V (Å3)
90
90
109.57(1)
90
106.25(1)
90
90
90
881.7(1)
4
901.9(3)
4
1942.7(2)
8
413.2(1)
2
Z
dcalc (g·cm−3
F(000)
)
1.520
1.618
1.626
1.794
1.911
416
448
976
102
236
θ range (°)
absorption coefficient, μ (mm−1
24.22
28.58
28.58
28.16
24.22
)
0.137
0.156
0.159
0.171
0.204
index ranges
−17 ≤ h ≤ 16
−10 ≤ k ≤ 10
−14 ≤ l ≤ 11
6042/3740
2.21
−16 ≤ h ≤ 16
−9 ≤ k ≤ 9
−13 ≤ l ≤ 13
8047/610
2.15
−12 ≤ h ≤ 12
−36 ≤ k ≤ 37
−10 ≤ l ≤ 10
36210/4779
2.54
−7 ≤ h ≤ 6
−6 ≤ k ≤ 5
−10 ≤ l ≤ 9
2255/901
4.30
−10 ≤ h ≤ 8
−5 ≤ k ≤ 6
−13 ≤ l ≤ 13
3774/947
4.12
no. of reflections collected/unique
int (%)
R
no. of parameters/restrains
GOF
51/3
51/3
289/0
64/0
86/4
1.135
1.086
1.043
1.073
1.109
R[F]/wR[F2] (I > 2σ(I))
R[F]/wR[F2] (all data)
max and min residual density/e·Å−3
4.03%/11.90%
4.53%/12.26%
+0.51/−0.26
3.02%/8.90%
3.70%/9.13%
+0.47/−0.21
3.52%/10.67%
5.31%/11.15%
+0.42/−0.33
6.45%/17.19%
9.40%/19.88%
+0.56/−0.53
5.54%/16.08%
7.58%/17.25%
+0.48/−0.36
Additionally, the optimized geometries were employed to estimate
the interaction energy of the selected dimers extracted from the crystal
lattice. The computations were performed in the supermolecular
approach within the CRYSTAL package at the DFT(B3LYP)/6-31G**
level of theory, taking into account the basis-set superposition error
(BSSE) and Grimme dispersion corrections (as implemented in the
CRYSTAL code).
AUTHOR INFORMATION
Corresponding Author
*E-mail: kdurka@gmail.com (K.D.); kwozniak@chem.uw.edu.
pl (K.W.).
■
Author Contributions
§Both authors contributed equally to this work.
(c). PIXEL Calculations. For the purpose of CRYSTAL data verifi-
cation, lattice energy were calculated in the OPiX package.17 The
geometry were taken from the CRYSTAL optimization. The obtained
structures were used to calculate the molecular electron density
distribution by the means of standard quantum-chemical methods
using the GAUSSIAN09 package at the MP2/6-31G** level of theory
(with suggested default options). The electron density was then
analyzed using the PIXEL module which allows for the calculation/
estimation of dimer and lattice energies. In a crystal lattice stabilization
energy computation a cluster of molecules within a radius of 20 Å was
used.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a grant from the National Science
Centre (DEC-2011/01/N/ST5/05592). Authors would like to
thank the Interdisciplinary Centre for Mathematical and Com-
putational Modelling in Warsaw (G33-14) and the Wrocław
Centre for Networking and Supercomputing for providing
computational facilities. R.K. also thanks the Foundation for
Polish Science for financial support within the “International
Ph.D. Projects” programme. We gratefully acknowledge the
Aldrich Chemical Co., Milwaukee, WI, USA, for a long-term
collaboration.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details regarding synthesis, crystallographic data
(residual density maps, geometrical parameters, CSD analysis),
and computational details, supplementary results (atomic
charges, scan parameters, geometries, energy considerations),
and all crystallographic information files (CIFs). The CCDC
numbers for the structures of fluorinated diboronic acids are
fluoro-1,2-phenylenediboronic acid (mF) - 882252; 2,6-difluoro-
1,4-benzenediboronic acid (26dF) - 882253; 2,5-difluoro-1,4-
phenylenediboronic acid (25dF) - 882254; tetrafluoro-1,2-phenyl-
enediboronic acid (tF) - 882255; 2,3-difluoro-1,4-phenylene-
diboronic acid (23dF) - 882256. This material is available free of
charge via the Internet at http://pubs.acs.org.
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