Hirshfeld surface analysis of substituted phenols

Article abstract of DOI:10.1021/cg1011605

The effect of para-substituents on the crystal packing of phenols has been investigated, for systems bearing nonpolar groups (tert-butyl and benzyl, compounds 1 and 2, respectively) and for methylene linked bis-phenol bearing polar nitro groups (compound

Full text of DOI:10.1021/cg1011605

DOI: 10.1021/cg1011605
Hirshfeld Surface Analysis of Substituted Phenols
2010, Vol. 10
5302–5306
Adam D. Martin, Karel J. Hartlieb, Alexandre N. Sobolev, and Colin L. Raston*
Centre for Strategic Nano-Fabrication, School of Biomedical, Biomolecular and Chemical Sciences,
University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
Received September 1, 2010; Revised Manuscript Received October 15, 2010
ABSTRACT: The effect of para-substituents on the crystal packing of phenols has been investigated, for systems bearing
nonpolar groups (tert-butyl and benzyl, compounds 1 and 2, respectively) and for methylene linked bis-phenol bearing polar
nitro groups (compound 3). Remarkable for 1 and 2, the asymmetric unit has six molecules, which form infinite helical hydrogen
bonded arrays in the extended structures, whereas compound 3 bearing nitro groups coplanar with the phenol rings forms
almost columnar arrays. Hirshfeld surface analysis is used to show that despite packing in a nearly identical manner, 1 and 2 are
distinctly different in their interactions, and these structures are compared to compound 3, where the solid-state interactions are
dominated by the nitro moieties.
Introduction
Phenolic compounds feature in a wide variety of processes,
1
such as in self-assembly, the purification of nucleic acids,
2
3
and as key reagents in chemical synthesis. para-tert-Butyl-
phenol is well-known as the adhesive resin in Bakelite in com-
4
bination with formaldehyde and as the main phenol used for
5
preparing calix[n]arenes. Variations in solvent, base, and stoi-
chiometry allows access to para-tert-butylcalix[n]arenes where
6
the number of phenol units [n] can vary from 4 to 20. para-
Benzylphenol features in the base catalyzed condensation of
7
calix[n]arenes, affording a mixture of macrocycles, n=5-8, or
predominantly n=4, which forms solid-state inclusion com-
8
9
pounds with icosahedral ortho-carborane and C . para-Nitro-
phenol is a well-known intermediate in the synthesis of para-
60
Figure 1. Molecular structures of the compounds investigated in
this study.
10
cetamol, and 2,2-methylene bis(4-nitrophenol) has been used in
1
1
the preparation of nitrated “double calixarenes” and nitrated
12
macrocyclic polyethers. Substitution at the meta- and ortho-
positions of phenol also plays a significant role in phenol-based
chemistry, but the focus of the present work is on the para-
substitution because of the nexus with calixarenes.
during the solventless synthesis of the compound by grinding
para-nitrophenol with paraformaldehyde.
Compound 1 crystallizes in the triclinic space group P1,
with six molecules in the asymmetric unit. The large complex
asymmetric unit forsucha small molecule in part explains why
this important and abundant compound has not been pre-
viously structurally authenticated. For two crystallographically
independent molecules, the tert-butyl group is disordered over
two positions, each with a modeled occupancy of 0.50. Packing
Hirshfeld surface analysis is rapidly gaining prominence as
a powerful technique in understanding the nature of inter-
molecular interactions within a crystal structure using a
fingerprint plot. This allows easy identification of character-
1
3
istic interactions throughout the structures, or as a surface
1
4
around the molecule. A dnorm surface allows for easy
comparison of intermolecular contacts relative to van der
Waals radii by way of a simple red-white-blue color scheme.
Recently, this system has been applied to large macromole-
results in a continuous network of hydrogen bonding (OH
˚
O
3
3 3
2
.649(2)-2.691(2) A) involving the phenolic hydroxyl groups,
forming a helical array along the a axis (Figure 2a). The tert-
butyl groups are mostly oriented toward the phenyl ring of a
neighboring molecule, with some interactions, as evidenced in
the packing diagram.
1
5
cular structures such as para-alkylated calix[4]arenes, and
1
para-substituted calix[5]arenes as C70 complexes, inaddition
6
1
7
to smaller molecules such as 2-chloro-4-nitrbenzoic acid.
The Hirshfeld surface analysis shows a similar proportion
of O H contacts for each of the six molecules, ranging from
3
3 3
Results and Discussion
5
.6 to 6.0%. In all cases, the O H interactions are represented
3
3 3
by a spike in the bottom left (donor) area of the fingerprint plot
Figure 2b), which represents a phenolic oxygen interacting with
a neighboring phenolic hydrogen, forming the helical network
para-tert-Butylphenol, 1 (Figure 1), was crystallized by eva-
poration of a hot acetonitrile solution, para-benzylphenol, 2,
was crystallized by slow evaporation from a benzene solution,
and crystals of 2,2-methylene bis(4-nitrophenol), 3, were formed
(
of hydrogen bonds. The H O interactions are represented by
3 3 3
a spike in the bottom right region of the fingerprint plot, and
the proportion of H O interactions has a larger variance than
*To whom correspondence should be addressed. Fax: þ618 6488 1005.
E-mail: colin.raston@uwa.edu.au.
3 3 3
its O 3 3 3 H counterparts, ranging from 3.8 to 6.2%. Only one
r
pubs.acs.org/crystal
Published on Web 11/08/2010
2010 American Chemical Society

Article
Crystal Growth & Design, Vol. 10, No. 12, 2010 5303
Figure 2. (a) Packing diagram, (b) Hirshfeld surface fingerprint plot, and (c) and the dnorm surface of p-tert-butylphenol, 1.
molecule displays a higher proportion of H 3 3 3
O than O
H
common for molecular structures crystallizing in the space
group Pna2 when Z > 4.
1
3 3 3
18
interactions, and this is due to two of its tert-butyl protons
interacting with a nearby phenolic oxygen. These oxygen-based
interactions represent the closest contacts in the structure and
can be viewed as a pair of large red spots on the dnorm surface
The Hirshfeld surface analysis shows that the proportion of
H interactions is similar for each of the six crystal-
O
3
3 3
lographically independent molecules, ranging from 4.9 to
5.9%, while the proportion of H O interactions range from
(
Figure 2c).
The “wings” seen in the plot belong to signature CH3 3 3 π
3
3 3
to 2..7 to 5.1%. The nature of the interactions are very similar
to those seen in compound 1, where the phenolic hydrogen
interacts with a neighboring phenolic oxygen, with hydrogen
interacting with another neighboring phenolic oxygen and so
forth, building a helical network of hydrogen bonds through-
out the structure. These short oxygen-based contacts are
identified once again on the dnorm Hirshfeld surface of the
molecules as large red spots (Figure 3b).
interactions, with the “wing” in the lower right of the finger-
print plot representing CH 3 3 3
π acceptor (or C H) interac-
3 3 3
tions. The proportion of C H interactions vary from 10.2 to
3
3 3
1
4.4% and are mainly due to neighboring tert-butyl groups
pointing toward the aromatic ring of the phenol moiety. H 3 3 3
interactions vary from 6.3 to 8.5% and are mainly due to
the tert-butyl groups, with one molecule displaying a larger,
more diffuse H C area in its fingerprint plot, and this relates
C
The C H and H C regions of the fingerprint plots for
3
3 3
3 3 3
3 3 3
to the methyl group being oriented into a void in the crystal
structure and is associated with a myriad of long contacts. Inter-
estingly, one of the molecules in the structure does not display any
this structure are notable in that four of the six unique mole-
cules are involved only in CH3 3 3 π acceptor or donor inter-
actions, not both, resulting in the appearance of only one
“
wings”, and thus, despite possessing C 3 3 3
H and H C inter-
3 3 3
“wing” in the fingerprint plot. The proportion of C
H
3 3 3
actions, no CH π acceptor or donor interactions are present.
interactions range from 17.8 to 20.7%, which is much larger
than that for compound 1. This can be directly attributed to
the nature of the para-substituent, with the benzyl group
resulting in more C H interactions than the tert-butyl
3
3 3
The majority of contacts, however, are due to H H interac-
3
3 3
tions, with these interactions making up 59.6 to 76.0% of the
Hirshfeld surface of these molecules. These contacts are mainly
due to the tert-butyl groups, although one of the molecules has
a short contact where an ortho-hydrogen interacts with a
proton from a neighboring tert-butyl group.
3
3 3
group in compound 1. The primary type of CH π interac-
3
3 3
tions arise from either a meta hydrogen from a neighboring
benzyl group pointing toward the phenyl aromatic ring or a
meta hydrogen from a neighboring phenyl group pointing
towarda neighboring benzyl aromaticring. The proportion of
p-Benzylphenol, 2, crystallizes in the orthorhombic space
group Pna2 , with the asymmetric unit remarkably also con-
1
sisting of six molecules (Z = 24). No solvents or disorder are
present in the structure. It packs in a manner very similar to that
H
of the interactions are similar to those described for C
C interactions vary from 11.5 to 18.6%, and the nature
H
interactions. A stunning feature of the Hirshfeld surface anal-
3
3 3
3
3 3
of compound 1, with a continuous network of hydrogen
˚
bonding (OH O 2.641(5)-2.670(5) A) in the form of a
ysis is the complementarity of the CH π donor and accep-
3
3 3
3 3 3
helical array down the b axis (Figure 3a). The replacement of
a tert-butyl group with a benzyl group possessing an aromatic
ring results in a larger proportion of CH π interactions.
tor regions for fingerprint plots of two separate molecules
(Figure 3c and d), where one molecule displays a strong
CH π donor “wing”, and a neighboring molecule displays
3
3 3
3 3 3
There is a pseudoinversion center, at 1/8, 1/2, 1/2, which is
a strong CH3 3 3 π acceptor “wing”.

5
304 Crystal Growth & Design, Vol. 10, No. 12, 2010
Martin et al.
Figure 3. (a) Packing diagram displaying the network of hydrogen bonding, (b) dnorm Hirshfeld surface, and (c and d) complementarity
of the CH π donor “wing” of one molecule (c, bottom right) with the CH π acceptor “wing” of another molecule (d, top left) in
compound 2.
3
3 3
3 3 3
The majority of the other contacts are H H interactions,
arises where the other oxygen from the same nitro group
interacts with a meta-hydrogen from a neighboring phenyl
unit. The most interesting interaction, however, is from the
other nitro group on the molecule, where both of the oxygen
atoms are involved in an interaction with a neighboring
phenolic hydrogen, which is oriented between the nitro
groups. This is responsible for a distinctive red double spot on
the dnorm surface (Figure 4c).
3
3 3
with the proportion of these varying from 50.9 to 59.2%,
which is notably less than that for compound 1, and again, it
relates to the presence of the benzyl substituent. Short con-
tacts arise where a meta-hydrogen interacts closely with a
neighboring methylene proton and where a meta-hydrogen
from a phenyl interacts with a meta-hydrogen from a neigh-
boring benzyl moiety.
Compound 3 crystallizes in the triclinic space group P1,
0
The proportion of C H interactions are similar to those
3
3 3
with two molecules of 2,2 -methylene bis(4-nitrophenol) in the
seen in compound 1, with these interactions comprising 9.7 and
10.0% of the Hirshfeld surface for each molecule. Two instances
of CH 3 3 3 π interactions are responsible for the “wings” which
are evident in the fingerprint plot, one where a neighboringmeta-
hydrogen is pointing toward the middle of one aromatic ring,
seen on the dnorm surface as a hexagonal-shaped red spot in
Figure 4d, and the other where a neighboring methylene proton
is oriented toward the center of the other aromatic ring of the
molecule. The H 3 3 3 C interactions are responsible for 7.4 and
8.9% of the Hirshfeld surface of the molecules and are the
reverse of the C 3 3 3 H interactions, which can be seen by the
symmetrical nature of this area in the fingerprint plot.
asymmetric unit (Z = 4). No solvents or disorder are observed
in the structure. Viewing the packing of the structure down
the b axis shows an almost columnar arrangement of molec-
ules, with the phenyl rings being angled at 114° relative to each
other, meaning that one phenyl group of the molecule is
oriented down the b axis, while the other phenyl group is
oriented almost orthogonal to this axis (Figure 4a). This com-
bined with the nitro groups being oriented opposite to each
other in the structure means that each nitro group interacts with
a hydroxyl from an orthogonal phenyl ring. Thus, unlike in
compounds 1 or 2, there is no helical arrangement of hydrogen
˚
bonding (OH O 2.781(5)-2.933(5) A), instead the hydrogen
It is noteworthy that H H interactions only represent a
3 3 3
3
3 3
bonding in the structure is limited to these “columns”. The
methylene linker between the phenol moieties plays a negligible
electronic role in the packing of this structure, the interactions
between the nitro groups dominating the orientation of the
phenol rings and the overall packing/cohesion of the structure.
Oxygen-based interactions play a much larger part in the
structure of compound 3 than in the structures of compounds
small part of the Hirshfeld surface, unlike for compounds 1 and
2. This is to be expected due to the nitro substituents, and
H
surface for both molecules. Short H H contacts result from
H interactions comprise only 18.2% of the Hirshfeld
3
3 3
3
3 3
two neighboring methylene hydrogens interacting with each
other, or two neighboring meta-hydrogen atoms interacting
with each other. Nevertheless, these two exceptions aside, the
H3 3 3 H interactions are mainly associated with long contacts.
1
and 2 due to the presence of the nitro substituent. The
proportion of O H interactions is 22.3 and 22.4% for the
O
O interactions make up 5.9 and 6.2% of the Hirshfeld
3
3 3
3 3 3
two molecules, and the proportion of H O interactions is
3
surface of the molecules in the structure, mainly for oxygen
atoms from the nitro group interacting directly with neighbor-
ing phenolic oxygens (involving hydrogen bonding). Another
interesting feature is the occurrence of C
3 3
1
9.1 and 20.3%. One of the prominent short contacts is due to
an oxygen from a nitro group interacting with a hydrogen
from a neighboring phenolic group. Another short contact
3 3 C interactions,
3

Article
Crystal Growth & Design, Vol. 10, No. 12, 2010 5305
Figure 4. (a) Packing diagram, (b) fingerprint plot, (c) dnorm surface displaying the “double spot” due to an O
surface displaying a CH π donor and acceptor contacts for compound 3.
3 3 H interaction, and (d) dnorm
3
3
3 3
which are responsible for 5.4 and 5.7% of the Hirshfeld
surface, revealing the presence of π π stacking within the
about 100 K on an Oxford Diffraction Gemini-R Ultra CCD
˚
R
diffractometer using monochromatized Cu-K (λ=1.54178 A).
3
3 3
Data were corrected for Lorentz and polarization effects and
absorption correction applied using multiple symmetry equivalent
reflections. The structure was solved by the direct method and refined
structure. In each molecule, there are two instances of C
interactions for each phenyl ring, one due to a CH
interaction and one due to a π π interaction.
C
π
3
3
3 3
3 3
2
19
3
3 3
on F using the SHELX-97 crystallographic package and X-Seed
20
interface. A full matrix least-squares refinement procedure was used,
We have shown that the para-phenol substituents play a
significant role in the solid state behavior of the three
phenol compounds, and for 1 and 2, this is despite their
very similar packing motifs. Compounds 1 and 2 form
infinite O HO hydrogen bonded helical arrays, in con-
2
2
2
2
2
-1
minimizing w(F
o
- F
c
), with w = [σ (F
o
) þ (AP) þ BP] , where
2
2
P=(F
{
o
þ2F
c
)/3. Agreement factors (R=Σ||F
o
|-|F ||/Σ|F |, wR2=
c
o
2
o
2 2
2 2 1/2
2
o
2 2
1/2
Σ[w(F
-F
c
) ]/Σ[w(F
o
) ]} , and GOF={Σ[w(F
-F ) ]/(n-p)} )
c
are cited, where n is the number of reflections and p the total number of
parameters refined. Non-hydrogen atoms of nondisordered fragments
were refined anisotropically using all reflections. The positions of
hydrogen atoms partly were localized from the difference Fourier
map and partly calculated from geometrical consideration, and their
atomic parameters were constrained to the bonded atoms during the
refinement. Hirshfeld surface analysis was undertaken using Crystal-
3
3 3
trast to the typical cyclic hydrogen bonded arrays when the
same molecules are condensed with formaldehyde in form-
ing the ubiquitous calixarene macrocycles. Hirshfeld sur-
face analyses revealed that (i) a tert-butyl moiety results in
dominant H H interactions, (ii) a benzyl moiety results in
3
3 3
21
Explorer 2.1. CCDC deposition numbers are 787583-787585.
Crystal/Refinement Details for 1. C10H14O, M=150.21, colorless
dominant carbon-based interactions, and (iii) a nitro moi-
ety results in the prevalence of oxygen-based interactions,
noting that such information is not readily apparent from
conventional analysis of the crystal packing diagrams
alone. All three compounds investigated in this study are
important precursors for calixarenes and other supramole-
cular architectures, and understanding the behavior of
these monomeric units themselves provides valuable insight
into the solid-state behavior of larger molecules which
covalently incorporate these compounds.
wedge 0.43 ꢀ 0.17 ꢀ 0.13 mm, F(000)=984 e, triclinic, P1 (No. 2),
˚
Z=12, T=100(2) K, a = 6.2213(2), b=11.9145(4), c=37.398(1) A,
3
˚
R = 98.779(3), β = 93.944(2), γ = 93.235(2)°, V = 2726.81(15) A ;
-
3
c
D =1.098 g cm ; sinθ/λmax=0.5946; N(unique)=9614 (merged from
4
3172, Rint=0.0376, Rsig=0.0561), N
wR2=0.1458 (A,B=0.09, 0.0), GOF=1.001; |ΔFmax|=0.49(4) e A
Crystal/Refinement Details for 2. C13 12O, M=184.23, colorless
needle 0.33 ꢀ 0.09 ꢀ 0.05 mm, F(000)=2352 e, orthorhombic, Pna2
o
(I > 2σ(I))=5677; R=0.0559,
-3
˚
.
H
1
(
No. 33), Z = 24, T=100(2) K, a = 42.858(3), b = 6.0745(3),
3
-3
˚
˚
c = 23.1726(11) A, V = 6032.8(6), A ; D = 1.217 g cm ; μCu
c
=
-
1
0
5
0
.589 mm ; sinθ/λmax =0.5877; N(unique)=5246 (merged from
7834, Rint =0.0843, Rsig =0.0363), N (I > 2σ(I ))=3940; R=
.0524, wR2=0.1324 (A,B = 0.10, 0), GOF=1.006; |ΔFmax|=
Experimental Section
o
-3
˚
All compounds used in this study were purchased from commer-
cial sources and used without further purification.
Crystallography. For compound 1, the X-ray diffracted intensi-
0.31(5) e A
.
10 2 6
Crystal/Refinement Details for 3. C13H N O , M = 290.23, red
needle 0.12 ꢀ 0.06 ꢀ 0.05 mm, F(000) = 600 e, triclinic, P1 (No. 2),
3
˚
ties were measured from a single crystal, 0.43 ꢀ 0.17 ꢀ 0.13 mm , at
Z=4, T=100(2) K, a=9.547(7), b=11.459(4), c=12.227(6) A, R=
3
-3
˚
about 100 K on an Oxford Diffraction Xcalibur CCD diffrac-
˚
75.44(3), β= 89.25(5), γ=71.88(4)°,V=1227.5(11) A ;D
c
=1.571gcm
;
=
tometer using monochromatized Mo-K
For compounds 2 and 3, the X-ray diffracted intensities were
R
(λ = 0.71073 A.)
sinθ/λmax=0.5878; N(unique)=4129 (merged from 15247, Rint
0.1051, Rsig=0.1849), N
0.0984 (A,B=0.02, 0), GOF=1.002; |ΔFmax|=0.24(6) e A
o
(I>2σ(I ))=1499; R=0.0553, wR2=
3
-3
˚
measured from a colorless single crystal, 0.33 ꢀ 0.09 ꢀ 0.05 mm , at
.

5
306 Crystal Growth & Design, Vol. 10, No. 12, 2010
Martin et al.
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(
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(
(
Supporting Information Available: Crystallographic information
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(
12) Gunduz, N.; Kilic, Z. Tetrahedron 1986, 42, 137.
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