Halogen- and hydrogen-bonded salts and co-crystals formed from 4-halo-2,3,5,6-tetrafluorophenol and cyclic secondary and tertiary amines: Orthogonal and non-orthogonal halogen and hydrogen bonding, and synthetic analogues of halogen-bonded biological systems

Article abstract of DOI:10.1002/chem.201402128

Co-crystallisation of, in particular, 4-iodotetrafluorophenol with a series of secondary and tertiary cyclic amines results in deprotonation of the phenol and formation of the corresponding ammonium phenate. Careful examination of the X-ray single-crystal structures shows that the phenate anion develops a C=O double bond and that the C-C bond lengths in the ring suggest a Meissenheimer-like delocalisation. This delocalisation is supported by the geometry of the phenate anion optimised at the MP2(Full) level of theory within the aug-cc-pVDZ basis (aug-cc-pVDZ-PP on I) and by natural bond orbital (NBO) analyses. With sp² hybridisation at the phenate oxygen atom, there is strong preference for the formation of two non-covalent interactions with the oxygen sp² lone pairs and, in the case of secondary amines, this occurs through hydrogen bonding to the ammonium hydrogen atoms. However, where tertiary amines are concerned, there are insufficient hydrogen atoms available and so an electrophilic iodine atom from a neighbouring 4-iodotetrafluorophenate group forms an I...O halogen bond to give the second interaction. However, in some co-crystals with secondary amines, it is also found that in addition to the two hydrogen bonds forming with the phenate oxygen sp² lone pairs, there is an additional intermolecular I...O halogen bond in which the electrophilic iodine atom interacts with the C=O π-system. All attempts to reproduce this behaviour with 4-bromotetrafluorophenol were unsuccessful. These structural motifs are significant as they reproduce extremely well, in low-molar-mass synthetic systems, motifs found by Ho and co-workers when examining halogen-bonding interactions in biological systems. The analogy is cemented through the structures of co-crystals of 1,4-diiodotetrafluorobenzene with acetamide and with N-methylbenzamide, which, as designed models, demonstrate the orthogonality of hydrogen and halogen bonding proposed in Ho's biological study.

Full text of DOI:10.1002/chem.201402128

DOI: 10.1002/chem.201402128
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&
Halogen Bonding
Halogen- and Hydrogen-Bonded Salts and Co-crystals Formed
from 4-Halo-2,3,5,6-tetrafluorophenol and Cyclic Secondary and
Tertiary Amines: Orthogonal and Non-orthogonal Halogen and
Hydrogen Bonding, and Synthetic Analogues of Halogen-Bonded
Biological Systems
Akihiro Takemura, Linda J. McAllister, Sam Hart, Natalie E. Pridmore, Peter B. Karadakov,
Adrian C. Whitwood, and Duncan W. Bruce*[a]
Abstract: Co-crystallisation of, in particular, 4-iodotetrafluor-
ophenol with a series of secondary and tertiary cyclic amines
results in deprotonation of the phenol and formation of the
corresponding ammonium phenate. Careful examination of
the X-ray single-crystal structures shows that the phenate
anion develops a C=O double bond and that the CÀC bond
lengths in the ring suggest a Meissenheimer-like delocalisa-
tion. This delocalisation is supported by the geometry of the
phenate anion optimised at the MP2(Full) level of theory
within the aug-cc-pVDZ basis (aug-cc-pVDZ-PP on I) and by
natural bond orbital (NBO) analyses. With sp2 hybridisation
at the phenate oxygen atom, there is strong preference for
the formation of two non-covalent interactions with the
oxygen sp2 lone pairs and, in the case of secondary amines,
this occurs through hydrogen bonding to the ammonium
hydrogen atoms. However, where tertiary amines are con-
cerned, there are insufficient hydrogen atoms available and
so an electrophilic iodine atom from a neighbouring 4-iodo-
tetrafluorophenate group forms an I···O halogen bond to
give the second interaction. However, in some co-crystals
with secondary amines, it is also found that in addition to
the two hydrogen bonds forming with the phenate oxygen
sp2 lone pairs, there is an additional intermolecular I···O halo-
gen bond in which the electrophilic iodine atom interacts
with the C=O p-system. All attempts to reproduce this be-
haviour with 4-bromotetrafluorophenol were unsuccessful.
These structural motifs are significant as they reproduce ex-
tremely well, in low-molar-mass synthetic systems, motifs
found by Ho and co-workers when examining halogen-
bonding interactions in biological systems. The analogy is
cemented through the structures of co-crystals of 1,4-diiodo-
tetrafluorobenzene with acetamide and with N-methylbenza-
mide, which, as designed models, demonstrate the ortho-
gonality of hydrogen and halogen bonding proposed in
Ho’s biological study.
Introduction
polarisable halogens, namely bromine and iodine, and to some
extent this has slowed its extension into the arena of biol-
ogy.[16] Thus, whereas iodine is an essential trace element
owing to its role in thyroid hormones in animals, bromine is
not an essential element and its functions can be replaced by
chlorine when it is not available.
As well as being a now widely used tool in supramolecular
chemistry,[1–5] halogen bonding has been used in the formation
of liquid crystals,[6] and is implied in studies in, for example,
non-linear optics,[7,8] gels,[9] anion recognition,[10] magnetic and
conducting materials,[11] separation of a,w-diiodoalkanes,[12]
porous materials[13,14] and catalysis.[15] As is well known, halo-
gen-bonding interactions tend to be strongest with the most
Nonetheless, there are many known halogenated metabo-
lites including antibiotics and it is also known that certain in-
flammatory responses can lead to oxidative halogenation of
proteins and amino acids. The possible structural role of halo-
gens in biological systems has been looked at in some detail
by Ho and co-workers,[17] who identified a dominant interac-
tion, namely the approach of the halogen atom to the p-
system of the carboxyl oxygen atom of an amide link—an in-
teraction that had little precedent in the literature. These au-
thors then went on to show how hydrogen and halogen
bonds to such carbonyl oxygen atoms could be regarded as
orthogonal, providing examples where both were found simul-
taneously.[18] These important, original studies have led to
wider interest.[19]
[a] A. Takemura, L. J. McAllister, S. Hart, N. E. Pridmore, Dr. P. B. Karadakov,
Dr. A. C. Whitwood, Prof. Dr. D. W. Bruce
Department of Chemistry, University of York
Heslington, York YO10 5DD (UK)
E-mail: duncan.bruce@york.ac.uk
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402128.
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons At-
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medium, provided the original work is properly cited.
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between the iodine atom and the ether oxygen atom of
a neighbouring stilbazole, forming a non-covalent, polymeric
motif. Interested then to explore further the balance between
hydrogen and halogen bonding in this phenol, we produced
a number of co-crystals with cyclic secondary and tertiary
amines and in so doing, provided low-molar-mass analogues
of the halogen-bond motifs found in biology as described by
Ho and co-workers.[17,18]
Results
Crystal and molecular structures
Crystals were produced by co-crystallising 4-iodotetrafluoro-
phenol, 4-bromotetrafluorophenol or pentafluorophenol with
the appropriate base in the solvent/anti-solvent system given
in Table 2, typically using base/phenol ratios of 1:1. The new
salts and co-crystals are shown in Figure 2 and crystallographic
data are collected in Table S1 in the Supporting Information.
Figure 1. Halogen-bonding interactions with ketones. The interaction motif
found in (a) acetone/Br2 and (b) 1,4-diiodotetrafluorobenzene with a bis-4-
(N,N-dimethylamino)benzophenone.
The study of interactions of halogens with carbonyl oxygen
atoms goes back to the work of Hassel and Strømme who, in
1959, described the formation of a polymer between Br2 and
acetone,[20] where bromine bridged between two acetone mol-
ecules to form the repeating motif (Figure 1). The angle at the
oxygen atom was reported as 1108, whereas the Br-Br-O angles
were strictly linear. The motif would suggest that the oxygen
atom uses sp2 orbitals in the bonding, although a recent theo-
retical study questions this.[21] A similar polymeric motif is de-
scribed when the ketone is found in 4,4’-bis(N,N-dimethylami-
no)benzophenone and the dihalogen is 1,4-diiodotetrafluoro-
benzene.[22]
Salts of pentafluorophenol
Piperidinium pentafluorophenate (1)
The complex crystallised with the expected 1:1 stoichiometry
and the positions of the hydrogen atoms on the nitrogen were
confirmed by difference mapping, whereas all the positions of
all other hydrogen atoms were calculated and refined by using
a riding model. The piperidine deprotonated the pentafluoro-
phenol (in contrast to the co-crystal with aniline where both
components were neutral[28]) and the crystallised salt exists as
a 2:2 dimer in which two of the phenate anions are held to-
gether by hydrogen bonds to the two NÀH hydrogen atoms
on each of the secondary ammonium cations (Figure 3a). This
gives a bifurcated motif at oxygen and leads to the formation
of a hydrogen-bonded, eight-membered ring arrangement in-
volving two nitrogen atoms, two oxygen atoms and four hy-
drogen atoms, in which all atoms are close to being co-planar.
The two oxygen atoms are not opposed directly and the C-
O···O angle is found to be 173.958. The NÀH lengths are equiv-
alent at about 1.8 ꢁ and the two hydrogen atoms binding to
oxygen make an angle of 96.328.
More recently, intermolecular C=O···Br interactions were
found to direct the crystal structures of o-bromoaromatic alde-
hydes,[23] whereas halogen bonding between carbonyl oxygen
atoms and bromine has been found to induce phosphores-
cence in organic compounds, namely with 2,5-dihexyloxy-4-
bromobenzaldhyde[24] and a tert-butoxycarbonyl (Boc)- and
N,N-dicyclohexylurea-capped g-amino acid with a bromo sub-
stituent.[25]
Described as a ‘small-molecule analogue’ of the orthogonal
interactions observed in biological systems, El-Sheshtawy et al.
reported the structures of a cucurbit[6]uril containing either
Br2 or I2 inside the cavity.[26] However, examination of the
lengths of the I···O and Br···O separations (99% of the sum of
The structure propagates in the direction perpendicular to
the fluorophenyl rings, which stack upon one another with
a plane-to-plane separation of 3.310 ꢁ to give the motif shown
in Figure 3b. The apparent ‘voids’ to either side of the main
the van der Waals radii), the magnitudes of the IÀI···O and BrÀ stack are occupied by neighbouring stacks that are out of reg-
Br···O angles (major deviations from linearity) and the space-fill-
ing model rather suggest a simple inclusion complex stabilised
by weak dispersion forces.
ister.
4-(N,N-Dimethylamino)pyridinium pentafluorophenate···penta-
fluorophenol (2) and 4-(pyrrolidino)pyridinium pentafluoro-
phenate···pentafluorophenol (3)
The molecule 4-iodotetrafluorophenol can act as both halo-
gen-bond and hydrogen-bond donor. The phenol readily forms
2:1 complexes with 4-alkoxystilbazoles that have liquid crystal
properties,[27] but use of a 1:1 ratio of the two components
leads to a 1:1 co-crystal in which the stilbazole hydrogen
bonds preferentially to the iodophenol. However, the extreme-
ly electrophilic nature of iodine clearly demands electron den-
sity and the single-crystal structure showed a halogen bond
As expected, in 2 the phenol is deprotonated by the 4-(N,N’-di-
methylamino)pyridine (DMAP) and the NÀH hydrogen atom
forms a hydrogen bond to the phenate oxygen atom at a dis-
tance of 1.84(2) ꢁ. However, examination of the structure re-
veals that it crystallises with an additional molecule of penta-
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fluorophenol and that this phenolic hydrogen atom forms a hy-
drogen bond to the oxygen atom of the phenate anion, a hy-
drogen bond that, at 1.68(3) ꢁ, is just shorter statistically than
that to the pyridinium hydrogen atom (Figure 4). The dihedral
angle between the aromatic ring
and the phenolic hydrogen
atom is 9(1)8, whereas it is
25.4(8)8 when the NÀH hydro-
gen atom is considered; the
angle made at the phenate
oxygen atom by the two hydro-
gen-bonded hydrogen atoms is
119(1)8. Also of note is that the
angle made between the planes
of the two phenolic rings makes
them close to co-planar (8.58),
whereas the [DMAPH]+ ring
makes an angle of 68.038 to the
phenate ring (Figure S1a in the
Supporting Information).
In 3, the phenol is again de-
protonated by the tertiary amine
and, in common with the struc-
ture of 2, the cation–anion pair
co-crystallise with a molecule of
pentafluorophenol (Figure 4b).
The OÀH···O hydrogen bond at
a value of 1.56(3) ꢁ is again
shorter than the NÀH···O hydro-
gen bond at 1.79(2) ꢁ. In this
structure, the cation ring is now
closer to the plane of the phen-
ate ring with the two intersect-
ing with an angle of 17.858 and
the two phenolic rings making
a larger angle of 46.948 (Fig-
ure S1b in the Supporting Infor-
mation).
Salts of 4-iodo-2-3-5-6-tetra-
fluorophenol
Piperazine-1,4-diium 4-iodote-
trafluorophenate (4)
The complex crystallised as a 2:1
(anion/cation) salt as both nitro-
gen atoms of the piperazine
were protonated to give a dicat-
ion. The basic motif is described
by a polymeric arrangement in
which two ‘opposing’ phenates
are held together by two pipera-
zine dications with a cationic
+
NH2 group hydrogen bonding
to the two oxygen atoms (dO···H
=
1.774(1) and 1.863(1) ꢁ—there is
a formal inversion centre), giving
an eight-membered ring em-
bracing two dications and two
Figure 2. Molecular formulae of the salts and co-crystals described in this paper.
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Figure 6. The basic polymeric repeat unit in 5.
Figure 3. (a) Hydrogen-bonded [2+2] dimer of salt 1 (hydrogen bonds
drawn in black). (b) Packing motif in 1.
the same length (approximately 1.8 ꢁ), but the torsion angles
with respect to the six-membered ring differ. Thus, the torsions
described by C11-C10-O2-H4 and by C15-C10-O2-H2 are 10(3)8
and 3(3)8, respectively, whereas those described by C1-C2-O1-
H1 and by C6-C1-O1-H3 are 16(3)8 and 44(3)8, respectively. The
less planar arrangement at O1 is understood as there is a long
contact (2.434(3) ꢁ) to the CÀH (on the C4 carbon) of a neigh-
bouring imidazole (Figure S3 in the Supporting Information),
which sits with a torsion angle of 53.3(4)8 with respect to C6-
C1-O1. There is no such interaction at O2. The two H···O···H
angles are also different, with that at O2 being 104(3)8 whereas
that at O1 is larger at 116(3)8. Further details of the crystal
packing are found in the Supporting Information and in Fig-
ure S4.
Figure 4. Molecular structures of (a) 2 and (b) 3.
Dibutylammonium iodotetrafluorophenate (6)
Dibutylammonium iodotetrafluorophenate crystallised in the
space group I2/m as a simple 1:1 salt in which two cations and
two anions hydrogen bond together to form an eight-mem-
bered ring. Two views are shown in Figure 7, with Figure 7a
showing the antiperiplanar arrangement in the dibutylammo-
nium cation, which is, perhaps, better viewed as a 4-azano-
nane. The packing arrangement is shown in Figure S5 (see the
Supporting Information).
Figure 5. Two views of the polymeric motif of complex 4: (a) Side view and
(b) top view.
phenates with the H···O···H angle as 107.37(7)8. Note that the
two aromatic rings are not coplanar (Figure 5a). The other end
of each dication participates in an identical bonding pattern,
leading to the basic polymeric unit (Figure 5b) and it can be
seen that the aromatic rings form a staircase-like arrangement.
Other details of the crystal packing in 4 are shown in Figure S2
(see the Supporting Information).
Figure 7. Two views of the hydrogen-bonded unit in 6: (a) View looking
down the ‘axis’ of the dibutylammonium chains and (b) at an angle to show
the NÀH···O hydrogen bonds.
Imidazolium iodotetrafluorophenate (5)
The asymmetric unit contained two pairs of molecules, which
were related symmetrically by a 1808 rotation, although the
axis of rotation did not correspond to a crystallographic axis.
CÀH hydrogen atoms were placed by using a riding model,
with the acidic hydrogen atoms being located by difference
mapping after all other atoms were located and refined.
Thiomorpholinium iodotetrafluorophenate (7)
The material crystallised as a 1:1 salt and, in common with the
structures of the imidazolium and piperazine-1,4-diium salts of
iodotetrafluorophenol, the basic structural motif showed a bi-
furcated motif for the hydrogen bonding at the oxygen atoms.
Also in common with the salt of piperazine, the second hydro-
gen atom of the secondary ammonium cation took part in
The structure propagates as a hydrogen-bonded polymer
with the hydrogen bonding describing a bifurcated motif at
each phenate oxygen atom, of which are of two types. Thus,
in Figure 6, all of the hydrogen bonds shown are statistically
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between the ammonium hydrogen atoms and two phenate
oxygen atoms with dH···O =1.79 ꢁ and H···O···H angle of 948.
However, what is totally unexpected is that each oxygen atom
also forms a halogen bond with iodine perpendicular to the
plane of the phenate anion and, as shown in Figure 10b, one
of these halogen bonds is above the plane of the dimer and
the other below it. In each case, the halogen bond length is
3.043(1) ꢁ—87% of the sum of the van der Waals radii.
The directionality of the halogen bond is shown in
Figure 11, where the two torsion angles made with respect to
the plane of the anion ring can be seen. The torsion angle il-
lustrated by Figure 11a and measured with respect to the
normal to the ring is found to be 16.58, whereas the C-O···I
angle (Figure 11b) is 105.2(1)8. Details of the crystal packing of
8, which shows an interesting grid structure defined by the
anions, are found in the Supporting Information and in Figur-
es S6–8.
Figure 8. The hydrogen-bonded motif in 7.
a similar interaction to give a hydrogen-bonded, eight-mem-
bered ring (Figure 8). Although not different statistically, the
hydrogen-bond lengths are noted as 1.85(2) and 1.71(3) ꢁ and
the H···O···H angle is 106(1)8.
Assembly of this dimeric arrangement into a polymeric
structure now brings halogen bonding into play, so that the
iodine atoms interact with the thiomorpholinium sulfur atoms
of neighbouring dimers to give the arrangement shown in
Figure 9. The S···I separation is 3.3085(6) ꢁ (87.5% of the sum
Figure 9. Polymeric arrangement in 7 viewed down the b axis and showing
the I···S halogen bonds.
Figure 11. Two views illustrating the directionality of the I···O halogen bond
in 8.
of the two van der Waals radii) and the halogen-bond angle at
iodine is 172.19(5)8. The directionality of the interaction with
sulfur is consistent with a classical view of the position of non-
bonded (lone) pairs of electrons on the sulfur atoms, although
it should be noted that the C-S···I angles are unsymmetric,
being found at 87.81(7)8 and 107.79(7)8. The polymer propa-
gates in the ac plane and there are no structurally significant
interactions to neighbouring chains in either the a or b direc-
tions.
Morpholinium iodotetrafluorophenate (9)
In common with the above structures, a hydrogen-bonded
dimer is formed involving two cations and two anions, except
that in 9 these dimers are distinct. In each case there are hy-
drogen-bond lengths of 1.93(3) and 1.77(3) ꢁ; the hydrogen
bonds are equal statistically, but differ in the H···O···H angles,
which take the values 938 and 1038. In common with the struc-
ture of the pyrrolidinium salt 8, I···O halogen bonds are found
(Figure 12) and it was found that halogen bonding involves
Pyrrolidinium iodotetrafluorophenate (8)
Being the salt of a secondary amine, this material forms the ex-
pected dimer supported by hydrogen bonding (Figure 10a)
Figure 12. Two views of the halogen-bonding interactions in the hydrogen-
bonded cation–anion dimers in 9. The two views relate to one another
through a 908 rotation.
Figure 10. (a) The hydrogen-bonded dimer in 8. (b) Side view of the dimer
showing the I···O halogen bonds.
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only the cation–anion rings that have the more acute angle.
Thus, it is in these dimers that the phenate oxygen atoms in-
teract to form halogen bonds and it is the iodine atoms of the
same phenate anion that interact with subsequent dimers
forming halogen bonds. There are no close contacts involving
the other, distinct cation–anion dimer. The I···O halogen bonds
are found to be 3.053(1) ꢁ in length (87% of the sum of the
van der Waals radii) and the C-I···O angle is 164.06(5)8. The crys-
tal packing in 9, which also shows an anion-grid structure akin
to that in 8, is described in the Supporting Information and in
Figure S9.
Figure 14. Partial structure of 11 showing both the hydrogen- and halogen-
bonding interactions.
4-(N,N-Dimethylamino)pyridinium iodotetrafluorophenate (10)
and 4-(pyrrolidino)pyridinium iodotetrafluorophenate (11)
protonated and the I···O distance is longer at 3.091(10) ꢁ, no
doubt owing to its interaction with the neutral phenol rather
than the anionic phenate ligand.
Being a tertiary amine, protonated DMAP offers only one hy-
drogen atom for hydrogen bonding, which binds to the phen-
ate oxygen atom in the plane of the iodotetrafluorophenate
ring. As found earlier with salts 2 and 3, the phenate oxygen
atom clearly prefers to bind to two electrophilic entities and so
in the absence of another hydrogen atom, this role is fulfilled
by the iodine atom of a neighbouring phenate anion to give
the arrangement shown in Figure 13a, where dI···O =2.993(1) ꢁ
Containing the 4-(pyrrolidino)pyridinium cation, 11 crystal-
lised in a manner similar to that of 10 (Figure 14); the N···H hy-
drogen bond is 1.79(4) ꢁ long, whereas the O···I halogen bond
is found to be 2.884(2) ꢁ. This latter distance is 82% of the
sum of the van der Waals radii and so slightly shorter than that
in 11; the I···O···H angle is 100(1)8. The packing is also similar to
that in 11 and is shown in Figure S11 (see the Supporting In-
formation).
Salts of 4-bromo-2,3,5,6-tetrafluorophenol
Pyrrolidinium bromotetrafluorophenate (12)
The material crystallised as a 1:1 salt and shows the now-famili-
ar eight-membered, hydrogen-bonded ring with a bifurcated
hydrogen bonding motif at the phenate oxygen atoms
(Figure 15); the hydrogen-bond length is about 1.87 ꢁ with
the H···O···H angle being 105(1)8.
Figure 13. (a) View of complex 10 showing the O···H hydrogen bond and
I···O halogen bond. (b) The same unit viewed from the side to show its pla-
narity.
Figure 15. Arrangement of the hydrogen-bonded dimer of 12.
(85% of the sum of the van der Waals radii) and dO···H
=
The propagation of the structure is shown in Figure S12 (see
the Supporting Information) and it is noted that there are no
significant, intermolecular, structure-directing interactions and
no short contacts to bromine.
1.76(2) ꢁ; the I···O···H angle is 100.1(8)8. Figure 13b shows the
planarity of the arrangement in 10. In fact, there are two com-
plexes in the unit cell and whereas the hydrogen-bond lengths
are the same in each case, the other halogen bond is slightly
shorter at 2.973(1) ꢁ, although the I···O···H angle remains un-
changed at 100.1(8)8. The 2D packing is shown in Figure S10
(see the Supporting Information).
Thiomorpholinium bromotetrafluorophenate (13)
This material crystallises as the 1:1 salt, but although it shows
the same topological pattern of hydrogen bonding at the
phenate oxygen atom, this leads to formation of a linear poly-
mer and the eight-membered ring observed in all of the other
A topologically similar motif has been reported recently by
Aakerçy et al.[29] in co-crystals of 4-iodotetrafluorophenol with
3,3’-azobipyridine, although in this case the phenol remains
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Figure 16. The linear, hydrogen-bonded polymeric arrangement in 13.
structures of salts of secondary amines is absent (Figure 16).
More than that, the angle made at the oxygen atom by the
two ammonium hydrogen atoms is 136(1)8, whereas in the
structure of thiomorpholinium iodotetrafluorophenate (7) it is
106(1)8 and for pyrrolidinium bromotetrafluorophenate (12) it
is 105(1)8.
The structure propagates as shown in Figure 17a, whereby
there are Br···Br interactions with a Type 1 geometry, with the
Br···Br distance being found to be 3.3967(4) ꢁ (92% of twice
Figure 18. Aspects of the structure of 15: (a) Hydrogen-bonded sheet
formed by acetamide; (b) linking of the hydrogen-bonded acetamide sheets
by halogen bonding to 1,4-diiodotetrafluorobenzene; (c) ‘close-up’ showing
the hydrogen and halogen bonding at the amide oxygen atom; (d) packing
of 1,4-diiodotetrafluorobenzene viewed down the c axis.
(amide/diiodotetrafluorobenzene). As seen in Figure 18a, the
amide forms hydrogen-bonded sheets with the NÀH hydrogen
atoms and the carbonyl oxygen atoms, constituting the now
topologically familiar eight-membered ring structure that
arises from the arrangement of hydrogen-bonded, dimeric
acetamide units. This arrangement is distinct from those found
in the two crystal polymorphs of acetamide itself.[30] The N···H
separations are 2.06(3) and 2.16(3) ꢁ with the H···O···H angle of
76(1)8. These sheets are then held together through halogen
bonding as shown in Figure 18b, with the detail of the interac-
tion of an iodine atom with the amide oxygen atom shown in
Figure 18c. The I···O halogen bond length is 2.973(2) ꢁ (84.9%
of the sum of the van der Waals radii) with the C-I···O angle
being 176.54(8)8. There are two H···O···I angles of 90.9(8)8 and
86.5(9)8, whereas the C-O···I angle is 111.3(1)8. The packing of
the 1,4-diiodobenzene units is shown in Figure 18d, viewed as
looking down the c axis. The separation of the planes defined
by the aromatic rings is 3.294 ꢁ, although there are no short,
inter-planar interactions.
Figure 17. (a) Side-on view of the extended structure of 13 showing the
Type I Br···Br interactions. (b) Top view showing only the relative positions of
the bromotetrafluorophenate anions.
the van der Waals radius) and with an interaction angle at bro-
mine of 155.83(6)8. However, Figure 17a is slightly misleading
as it is not the case that the different bromotetrafluorophenate
rings are stacked one upon the other, rather they are slipped
with respect to one another, which is illustrated in Figure 17b.
The distance between the planes described by the anion rings
is 3.039 ꢁ.
Piperazine-1,4-diium 4-bromotetrafluorophenate (14)
This salt is all but isomorphous and isostructural with its iodo
analogue (3) and is not discussed further save to say that
there are no short contacts to bromine. Illustrative diagrams
appear in Figure S13 (see the Supporting Information).
N-Methylbenzamide/1,4-diiodotetrafluorobenzene (16)
The co-crystals formed also have a 2:1 N-methylbenzamide/
diiodotetrafluorobenzene stoichiometry, but with one proton
fewer than 15; it forms a one-dimensional chain through hy-
drogen bonding between the amide hydrogen atom and the
carbonyl group of an adjacent amide. The aromatic rings do
not sit one upon another, rather they propagate through the
crystal in a stepped arrangement, with the rings being formally
co-parallel every second molecule with a measured separation
of 6.348 ꢁ. This differs from the structure of N-methylbenza-
Co-crystals of 1,4-diiodotetrafluorobenzene with amides
Acetamide/1,4-diiodotetrafluorobenzene (15)
The crystallisation was set up with N-methylacetamide and 1,4-
diiodotetrafluorobenzene, but adventitious water caused hy-
drolysis to acetamide, which crystallised as a 2:1 co-crystal
Chem. Eur. J. 2014, 20, 6721 – 6732
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Discussion
Bonding in the phenate anions
When analysing the structures of the various salts described, it
quickly became apparent that in almost every case, the CÀO
bond of the phenate was shorter than might otherwise be ex-
pected, being found between 1.291(2) and 1.312(3) ꢁ. The only
exception was in the neutral pentafluorophenols in 2 and 3,
not discussed further, where the distances were 1.3391(17) and
1.335(2) ꢁ, respectively. The CÀO length in pentafluorophenol
itself is around 1.37 ꢁ (data exist for >1 polymorph).
Figure 19. Structure of 19 showing (a) the linear, hydrogen-bonded motif of
the methylbenzamide linked by 1,4-diiodotetrafluorobenzene and (b) detail
of the hydrogen and halogen bonding at the amide carbonyl oxygen atom.
The contraction is consistent with the development of C=O
p-bond character and prompted examination of the CÀC bond
lengths in the ring (Table 1). Thus, in all cases but 1 and 4,
there was evidence for changes in the CÀC bond lengths to
those of a structure that could be described as either fully de-
localised (Figure 20a: 2 (phenate ring), 3, 6, 7, 8, 13) or partial-
ly delocalised (Figure 20b: 5, 9, 10, 11, 12, 14). ‘Full delocalisa-
tion’ means that the C1ÀC2 bond was statistically longer than
both C2ÀC3 and C3ÀC4 bonds, whereas ‘partial delocalisation’
means that the C2ÀC3 bond was statistically shorter than
those of C1ÀC2 and C3ÀC4. The distinction between the two
classes takes the values of the estimated standard deviation
(esd) into account, which in turn depend on the R factor. That
said, it is felt that, in reality, probably all of the structures fall
into the ‘fully delocalised’ category. Interrogation of the Cam-
bridge Crystallographic Database shows rather few structures
mide itself, where the aromatic rings alternate from one side
of the hydrogen-bonded chain to the other.[31] Pairs of these
chains are then bridged by molecules of 1,4-diiodotetrafluoro-
benzene (Figure 19a), which form an I···O halogen bond in
which the I···O separation is 2.884(3) ꢁ (82.4% of the sum of
the van der Waals radii) with a C-I···O angle of 169.54(9)8 and
an I···O···H angle of 83.0(9)8. Note that in this case, the reduced
number of hydrogen atoms available for hydrogen bonding
means that each oxygen atom interacts with only one hydro-
gen atom and one iodine atom (Figure 19b), whereas in 15
there are two interactions with two hydrogen atoms. The crys-
tal packing in 16 is illustrated in Figure S14 (see the Support-
ing Information).
Table 1. Key phenate bond lengths [ꢁ] and bond angles [8] in the complexes studied. Atom numbers are those from Figure 20.
1
2
2
3
3
4
5
6
7
(phenol)
(phenate)
(phenol)
(phenate)
C1=O
C1ÀC2
1.311(3)
1.400(3)/
1.404(3)
1.384(3)/
1.373(3)
1.377(4)/
1.376(3)
1.3391(17)
1.390(2)/
1.400(2)
1.385(2)/
1.3874(19)
1.383(2)/
1.378(2)
1.3116(16)
1.406(2)/
1.414(2)
1.3866(19)/
1.3833(19)
1.377(2)/
1.384(2)
1.335(2)
1.392(2)/
1.384(2)
1.376(2)/
1.384(2)
1.370(2)/
1.374(2)
1.301(2)
1.402(2)/
1.404(2)
1.377(2)/
1.373(2)
1.377(2)/
1.372(2)
1.306(2)
1.405(3)/
1.409(3)
1.376(3)/
1.379(3)
1.385(3)/
1.390(3)
1.304(5)
1.412(5)/
1.409(5)
1.380(6)/
1.382(5)
1.388(5)/
1.395(6)
1.297(5)
1.404(4)
1.297(2)
1.406(3)/
1.408(3)
1.376(3)/
1.370(3)
1.387(3)/
1.389(3)
C2ÀC3
C3ÀC4
1.371(5)
1.379(4)
Angle
H···O···H
96
H···O···H
119
H···O···H
96
H···O···H
107
H···O···H
(polymer)
104
H···O···H
110
H···O···H
106
116
8[a]
9[a]
10
11
12
13
14
15
16
C1=O
C1ÀC2
1.298(2)
1.405(3)/
1.403(3)
1.376(3)/
1.374(3)
1.382(3)/
1.383(3)
1.3079(18)
1.406(2)/
1.402(2)
1.376(2)/
1.382(2)
1.385(2)/
1.381(2)
1.291(2)
1.406(2)/
1.412(2)
1.378(2)/
1.375(2)
1.395(2)/
1.375(2)
1.292(3)
1.409(3)/
1.413(4)
1.370(4)/
1.368(4)
1.386(3)/
1.390(4)
1.298(2)
1.417(3)/
1.407(3)
1.367(3)/
1.376(3)
1.385(3)/
1.393(3)
1.301(2)
1.404(3)/
1.406(3)
1.374(3)/
1.376(3)
1.382(3)/
1.378(3)
1.301(5)
1.413(6)/
1.406(6)
1.367(6)/
1.370(6)
1.400(6)/
1.385(5)
1.242(3)
–
1.240(2)
–
C2ÀC3
C3ÀC4
–
–
–
–
Angle
H···O···H
H···O···H
H···O···I
100
H···O···I
100
H···O···H
105
H···O···H
(polymer)
136
H···O···H
103
H···O···H
76
H···O···I
83
94
93
104
103
[a] For 8 and 9 there are two H···O···H angles as there are two, independent dimers in the asymmetric unit. In each case, the smaller value refers to the hy-
drogen-bonded dimer where there is, in addition, a halogen bond to iodine. In addition, each structure has two H···O···I angles: 8: 848 and 1148 and 9:
1068 and 1288.
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Figure 20. (a) The ‘fully’ delocalised and (b) the ‘partially’ delocalised bond-
ing motifs found in the various phenate anions. Note that C1, C2, etc., are
generic labels and that the actual atom numbers will vary from structure to
structure.
Figure 22. Electrostatic surface potentials for (a) 4-iodotetrafluorophenol and
(b) the 4-iodotetrafluorophenate anion mapped on the respective 0.03 Har-
tree–Fock (HF) total electronic density isosurfaces.
of the free pentafluorophenate anion where such delocalisa-
tion is observed, although the papers tend to contain no com-
ments. However, the Database also shows that such delocalisa-
tion is quite common in phenate anions.
electronic structures. Examples for 4-iodotetrafluorophenol/4-
iodotetrafluorophenate are given in Figure 22 (other ESPs are
included in Figure S16 in the Supporting Information). Depro-
tonation of the phenols to give the corresponding phenate
leads to a more negative potential around the oxygen atom
and, as the halogen in the para position becomes more polar-
isable, the potential around the halogen becomes more posi-
tive in the phenol. However, in the phenate, the positive elec-
trostatic potential around the halogen decreases and, in the
cases of F and Cl, becomes negative.
To probe this further, the geometry of pentafluorophenol, its
anion and the anion of both the 4-iodotetrafluorophenate and
4-bromotetrafluorophenate anions were optimised at the MP2-
(Full) level of theory and their electronic structures were sub-
jected to natural bond orbital (NBO) analyses. Cartesian coordi-
nates of the optimised geometries can be found in Table S3 of
the Supporting Information. Data were also obtained for 4-
chlorotetrafluorophenol/4-chlorotetrafluorophenate and 4-io-
dotetrafluorophenol and 4-bromotetrafluorophenol and are in-
cluded as Figure S15 for completeness (see the Supporting In-
formation). Thus, computational results (Figure 21) show the
shortening of the CÀO bond on ionisation and are also consis-
tent with a ‘fully’ delocalised structure.
Bonding motifs in the structures
In the discussion that follows, the ketonic nature of the CÀO
bond is important as it allows comparison with the interactions
between the amide carbonyl of a protein chain and bromo
compounds as discussed by Ho and co-workers.[17,18]
The results of the NBO analyses were utilised to probe fur-
ther the quinoidal type structure. In the case of the phenol,
the p-occupancies of the ring CÀC bonds were observed to be
between 1.67 and 1.71, which is consistent with a fully delocal-
ised structure with no p-occupancy of the CÀO bond. Howev-
er, in the phenate anion, the p-occupancy of the CÀO bond
became 1.99, whereas that for C2ÀC3 was found to be 1.79
and C1ÀC2 and C3ÀC4 were found not to have p-occupancy,
consistent with the quinoidal arrangement. A table containing
calculated NBO values for each phenol/phenate pair can be
found in the Supporting Information as Table S2.
The structures of all complexes with the exception of 10
and 11 reveal a strong preference for the phenate oxygen
atom to accommodate two hydrogen-bond donors in the
plane of the ring, so much so that in 2 and 3 a neutral penta-
fluorophenol co-crystallises to take up the second of these po-
sitions in the absence of a second ammonium hydrogen atom.
This is consistent with the phenate anion having developed
C=O bond character, which would lead to the presence of two
sp2 orbitals in the plane of the ring. This shows a parallel with
the co-crystal structures in Figure 1, where there are two halo-
gen bonds into lone-pair sp2 orbitals on a carbonyl oxygen
atom, and is consistent with experiments in the gas phase,
which showed that FCl will form a halogen bond with the lone
pairs of electrons of the carbonyl oxygen atom of formalde-
hyde with a C=O···Cl angle of 110.98.[32] Interaction with the
lone pairs of electrons was found to take precedence over in-
teractions with the p electrons.
Examination of the electrostatic surface potentials (ESPs) of
the phenols and phenates provides further insights into their
To probe this further, the HF molecular orbitals at the MP2-
(Full) optimised geometries were localised by using the Edmis-
ton–Ruedenberg localisation procedure. The results are illus-
trated for the iodotetrafluorophenate anion. Figure 23a and
b shows the presence of sp2 orbitals on oxygen, clearly consis-
tent with the strong preference shown in the crystal structures
for two hydrogen-bond donors bound to oxygen in the plane
of the ring.
The majority of cations used were secondary amines, mean-
ing that there were two NÀH hydrogen atoms at the cationic
centre and so formation of the [2+2], hydrogen-bonded dimer
Figure 21. MP2(Full)-optimised geometries: CÀC and CÀO bond lengths (in
ꢁ) of (a) pentafluorophenol, (b) the pentafluorophenate anion, (c) the 4-iodo-
tetrafluorophenate anion and (d) the 4-bromotetrafluorophenate anion.
Chem. Eur. J. 2014, 20, 6721 – 6732
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Figure 24. Possible arrangements of hydrogen and halogen bonding at
amide oxygen atoms showing (a) both in plane and (b) both out of plane
with respect the amide link. After Ho and co-workers.[18]
the same plane (Figure 24a), or both the halogen and hydro-
gen bond would be found bound to the oxygen in the plane
of the amide bond (Figure 24b). In the majority of cases, the
angle, a, was found to be between 75 and 908, leading them
to propose that the hydrogen and halogen bonds, when both
present, should be regarded as orthogonal. Indeed, this idea
was supported further by calculations, which showed that the
energy of a hydrogen bond between two amide units was un-
affected by the approach of the Br of bromobenzene to the
hydrogen-bond acceptor (oxygen), and, similarly, the energy of
interaction between the hydrogen-bond acceptor (oxygen)
and a halogen-bonded bromine atom was unaffected by the
length of the hydrogen bond to oxygen. For comparison, the
strength of one hydrogen bond to oxygen was affected appre-
ciably by the presence of a second hydrogen bond.
Figure 23. Representations of (a, b) the localised molecular orbitals (LMOs)
corresponding to the lone electron pairs on O and (c) the p orbital on the
C=O bond. The orbitals are represented as blue/red isosurfaces at orbital
values of Æ0.05 (e/bohr3)À1/2
.
is readily rationalised. However, use of a tertiary amine means
that there is only one such hydrogen atom available and so in
10 and 11, in-plane hydrogen and halogen bonds are formed
(Figures 13 and 14), whereas in the case of 5, there is a second
NÀH hydrogen atom available and so a linear polymer is seen
(Figures 6 and S4a in the Supporting Information), which also
provides for two hydrogen bonds at oxygen.
Then, considering 6 and 7, the presence of a secondary am-
monium cation allows for the formation of the [2+2] hydro-
gen-bonded dimer, but in the case of 7, the thiomorpholinium
cation also contains a sulfur atom that then forms a halogen
bond to the phenate iodine atom, leading to a polymeric
structure as shown in Figure 9.
To make an even more direct comparison between the bio-
logical and synthetic systems, this study allowed the amides N-
methylacetamide and N-methylbenzamide to co-crystallise
with 1,4-diiodotetrafluorobenzene. The N-methylacetamide hy-
drolysed during crystallisation to give acetamide and the struc-
ture of the resulting co-crystal (15) showed sheets made up of
hydrogen-bonded acetamides (Figure 18a) linked by the aro-
matic diiodide through I···O halogen bonding into the p-
system of the amide carbonyl group (Figure 18b). N-Methyl-
benzamide did not hydrolyse during crystallisation and the
structure also showed a one-dimensional, sheet-like arrange-
ment but with one hydrogen atom fewer available for hydro-
gen bonding. Again, I···O halogen bonding into the p-system
of the amide carbonyl held the sheets together.
However, in the case of 8 (pyrrolidium cation) and 9 (mor-
pholinium cation), although the expected [2+2] dimer is
indeed observed, examination of the structure shows that
there is also an intermolecular I···O halogen bond. This forms
between the iodine atom of a neighbouring iodotetrafluor-
ophenate anion (itself part of a [2+2] dimer) and a phenate
oxygen atom of the hydrogen-bonded dimer, with the iodine
atom approaching out of the plane of the phenate ring (Figur-
es 10b, 11 and 12). Interaction of the iodine atom with the
oxygen atom uses the p-system of the C=O bond as illustrated
in Figure 23c. So far as we are aware, such a combined hydro-
gen and halogen-bonding motif is without precedent in the lit-
erature of synthetic co-crystals.
These structures provide an excellent link between the bio-
logical systems and the co-crystal salts of the amine/phenol
combinations as now described. Thus the N-methylbenzamide
structure 16 mirrors the behaviour described by Voth et al. in
having effectively orthogonal halogen and hydrogen bonding
with an H···O···I angle of 83.08 (arrangement as in Figure 23b),
which agrees well with the modal angle they report in such
cases. Then there are the cases of 10 and 11, where in each
there is also a single hydrogen atom available for hydrogen
bonding and so both a hydrogen and halogen bond are seen
with the H···O···I angle=100(1)8 in each case. These can also be
regarded as orthogonal, but in this case they exist in the plane
of the phenate ring, an arrangement that would not be possi-
ble in 16 on steric grounds.
However, in 15, although there is also an I···O halogen bond
into the C=O p-system, there are, in addition, two hydrogen
bonds that bind into the lone-pair sp2 orbitals on the amide
oxygen atom, a motif that is not found in the biological sys-
tems as the amide link contains a single hydrogen atom avail-
able for hydrogen bonding and the close approach of two hy-
drogen atoms is likely disfavoured sterically. As noted already,
Comparison with the motifs described by Ho and co-workers
is then instructive. They first described systems mined from
the Protein Data Bank (PDB) in which there was halogen bond-
ing by Cl, Br or I to carbonyl oxygen atoms, almost all of which
were associated with amide links in the peptide chain. In these
cases and considering only the halogen···oxygen interaction,
iodine showed a very strong preference for binding into the p-
system of the C=O bond, whereas for bromine the preference
in favour of binding to the p-system over binding to the lone
pairs on oxygen was appreciably smaller, albeit over a smaller
data set.[17] They then went on to mine data from the PDB for
a series of protein–ligand combinations containing short X···O
interactions.[18] This study showed that when only hydrogen
bonding was present, the hydrogen bond formed preferential-
ly directly opposite to the C=O bond and, as such, in the plane
of the amide bond. However, in cases where there was both
hydrogen and halogen bonding to the oxygen atom, then
either the halogen would approach from the plane above the
amide bond and the hydrogen bond would be found below
Chem. Eur. J. 2014, 20, 6721 – 6732
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this motif is also found in 8 and 9. In these three structures,
the H···O···H angle in the [2+2] dimer is 768 (15) and 93.58 (8
and 9), whereas in structures of 4-halotetrafluorophenates
where there is a [2+2] dimer and no halogen bonding (4–7
and 12–14), then the same angle is in the range 100 to
1078.[33] Thus, in contrast to the calculations reported by Voth
et al., in this case the hydrogen and halogen bonding are not
orthogonal as it is evident that the H···O···H angle is apprecia-
bly smaller where there is additional I···O halogen bonding.
This is shown elegantly in the structures of 8 and 9, where in
each case there are two, independent [2+2] dimers and, in the
dimer where there is no halogen bond, the H···O···H angle is
103.58, whereas in the other (which is halogen bonded) the
angle is 93.58.[34]
ported by calculations at the MP2 level of theory and then ex-
plains the observation that the hydrogen-bonding motifs of
these phenates are dominated by interaction with the lone-
pair sp2 orbitals on the oxygen atoms. Where there are insuffi-
cient hydrogen atoms to allow formation of two hydrogen
bonds per oxygen atom, then both hydrogen and halogen
bonding into the sp2 orbitals is observed.
However, in some cases where there are already two hydro-
gen bonds to an oxygen atom, an additional I···O halogen
bond forms representing an interaction between the electro-
philic iodine atom of the 4-iodotetrafluorophenate and the p-
bonding orbital or the carbonyl group. The broader signifi-
cance of this observation is that not only is the motif without
precedent in studies of halogen-bonded materials, but it also
presents a synthetic analogy with observations of halogen
bonding in the structures of proteins as described by Ho and
co-workers.[16–18] Moreover, while the synthetic studies can re-
produce the orthogonality of hydrogen and halogen bonding
proposed by Ho and supported by calculation, they also show
that this orthogonality breaks down where there are simulta-
neously two hydrogen bonds and a halogen bond to oxygen.
Finally, structures obtained by using 4-bromotetrafluorophe-
nol do not reproduce these motifs, an observation that may
point to the greater importance of steric and allosteric factors in
determining intermolecular arrangements in protein systems.
In the original paper by Auffinger et al.[17] and to an extent
in the study by Voth et al.,[18] significant emphasis was placed
on biological Br···O halogen bonds, whereas this synthetic
study has concentrated on iodo materials. To this end, salts 12
to 14 were obtained and it is noteworthy that, save for the
Type I Br···Br interactions in 13 (Figure 17a), no other short
contacts to Br are seen. In general terms, halogen bonds to
bromine are expected to be weaker than iodine analogues and
one very simple illustration of this is in the comparison be-
tween the 2:1 complexes formed between 4-alkoxystilbazoles
and 1,4-diiodo- and 1,4-dibromo-tetrafluorobenezene. Thus, in
both cases 2:1 co-crystals are obtained, but only the complex
of the diiodotetrafluorobenzene showed liquid crystal proper-
ties as the analogous dibromotetrafluorobenzene complex fell
apart on heating, suggesting weaker halogen bonding.[35]
While it is recognised that there are many factors that can
affect the intermolecular interactions observed in a co-crystal
system, it is interesting that analogous halogen-bonding
motifs are not seen in any of 12 to 14. What this may point to
is the fact that in protein systems, interactions that form can
be a result of a range of steric and allosteric factors related to
secondary and tertiary structures, and indeed Voth et al. draw
attention to a-helices and b-sheets in their discussions.[18]
Therefore, although the structures reported here offer synthet-
ic analogues that can help in the interpretation and under-
standing of the halogen bonds found in proteins, it is clear
that the analogy cannot be taken too far given the structural
complexity in proteins at the secondary and tertiary level.
Of course, one might then go further and argue that in the
solid-state structures of molecular species, the importance or
not of any given intermolecular, interatomic contact(s) may be
a delicate function of the enthalpic contribution made to the
lattice energy when compared with the general driving force
for efficient molecular packing, which may lead to such inter-
actions occurring by accident rather than design.
Experimental Section
4-Iodotetrafluorophenol was prepared as described in the litera-
ture.[36] All other reagents were obtained commercially and were
used as obtained.
General remarks on co-crystallisation experiments
In a typical co-crystallisation experiment, vapour diffusion tech-
niques were used. The components were dissolved in a small
volume of common solvent, and placed inside a tablet tube inside
a vial and the tablet tube was then covered with aluminium foil,
which was punctured by using a needle. The anti-solvent (ca.
2 cm3) was added to the vial, which was then sealed with a cap
and covered in parafilm to prevent evaporation of the solvents.
Solvents and anti-solvents are given in Table 2.
Table 2. Solvent systems used in the crystallisations.
Solvent
Anti-solvent
1
2
3
dichloromethane
THF
THF
cyclohexane
cyclohexane
none
4
5
methanol
THF
toluene
hexane
6
7
8
9
10
11
12
13
14
15
16
THF
cyclohexane
iPr2O
methanol
chloroform
THF
cyclohexane
cyclohexane
diethyl ether
cyclohexane
none
none
none
none
none
Conclusion
THF
chloroform
acetonitrile
acetonitrile
THF
dichloromethane
dichloromethane
In this extensive and systematic study of salts and co-crystals
formed mainly between 4-halotetrafluorophenols and cyclic
amines, it is noted that in all cases the phenate ion formed
adopts a delocalised, Meissenheimer-like structure in which
double-bond character develops in the CÀO bond. This is sup-
Chem. Eur. J. 2014, 20, 6721 – 6732
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Full Paper
[16] M. R. Scholfield, C. M. V. Zanden, M. Carter, P. S. Ho, Protein Sci. 2013, 22,
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[17] P. Auffinger, F. A. Hays, E. Westhof, P. S. Ho, Proc. Natl. Acad. Sci. USA
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Single-crystal X-ray structures were determined as described else-
where;[37] CCDC deposition numbers are given in Table S1.
Computational procedure
[18] A. R. Voth, P. Khuu, K. Oishi, P. S. Ho, Nat. Chem. 2009, 1, 74–79.
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Diederich, Angew. Chem. 2011, 123, 329–334; Angew. Chem. Int. Ed.
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Keywords: co-crystallisation
bonding · 4-halotetrafluorophenols · hydrogen bonding
· crystal structure · halogen
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Received: February 11, 2014
Published online on May 5, 2014
Chem. Eur. J. 2014, 20, 6721 – 6732
www.chemeurj.org
6732 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim