NMR-crystallographic study of two-dimensionally self-assembled cyclohexane-based low-molecular-mass organic compounds

Article abstract of DOI:10.1039/c3ce41158c

Using a combined approach based on scanning electron microscopy, powder X-ray diffraction as well as 1D and 2D multinuclear solid-state NMR spectroscopy, we were able to determine the morphology and the crystal structures for a set of three supramolecular compounds with different hydrogen bonding motifs, namely N,N′-(cyclohexane-trans-1,4-diyl)bis(2,2- dimethylpropanamide) 1, 1,1′-(cyclohexane-trans-1,4-diyl)bis(3-tert- butylurea) 2 and N¹,N⁴-bis(tert-butylcarbamoyl) cyclohexane-trans-1,4-dicarboxamide 3. Based on a complete signal assignment of the 1D solid-state MAS NMR spectra (¹H, ¹³C, ¹⁵N) employing 2D HETCOR experiments and a quantitative evaluation of the corresponding resonances, the content of the asymmetric unit was determined to one half of a molecule. Probing the molecular configuration with ¹H-¹H double-quantum experiments revealed an intramolecular hydrogen bond for compound 3 while 1 and 2 form exclusively intermolecular H-bonds. Ab initio structure solutions applying real space methods with an included close-contact penalty were carried out for all compounds. The following Rietveld refinements led to excellent wR _p-values between 2.5% and 4.1%. Compounds 1 and 2 crystallise isostructurally in the monoclinic space group P2₁/c exhibiting a pseudo-biaxial hydrogen bond motif. 3 crystallises in the triclinic space group P1 with intermolecular head-to-tail hydrogen bonds connecting the molecules to one-dimensional ribbons. Nevertheless, all compounds grow in a sheet-like morphology with lateral dimensions of several hundred micrometres indicating a fast growth in two dimensions along two of the crystal axes. Since all three molecules possess inversion symmetry cancelling the molecular dipole moment the growth mechanism itself has to be dominantly driven by the formation of hydrogen bond networks.

Full text of DOI:10.1039/c3ce41158c

CrystEngComm
View Article Online
View Journal | View Issue
PAPER
NMR-crystallographic study of two-dimensionally self-
assembled cyclohexane-based low-molecular-mass
organic compounds†
Cite this: CrystEngComm, 2013, 15,
8784
Marko Schmidt,a Christoph S. Zehe,a Renée Siegel,a Johannes U. Heigl,b
b
b
a
*
Christoph Steinlein, Hans-Werner Schmidt and Jürgen Senker
Using a combined approach based on scanning electron microscopy, powder X-ray diffraction as well as 1D
and 2D multinuclear solid-state NMR spectroscopy, we were able to determine the morphology and the crystal
structures for a set of three supramolecular compounds with different hydrogen bonding motifs, namely
N,N′-(cyclohexane-trans-1,4-diyl)bis(2,2-dimethylpropanamide) 1, 1,1′-(cyclohexane-trans-1,4-diyl)bis(3-tert-butylurea) 2
and N1,N4-bis(tert-butylcarbamoyl)cyclohexane-trans-1,4-dicarboxamide 3. Based on a complete signal assign-
ment of the 1D solid-state MAS NMR spectra (1H, 13C, 15N) employing 2D HETCOR experiments and a quanti-
tative evaluation of the corresponding resonances, the content of the asymmetric unit was determined to one
half of a molecule. Probing the molecular configuration with 1H–1H double-quantum experiments revealed an
intramolecular hydrogen bond for compound 3 while 1 and 2 form exclusively intermolecular H-bonds. Ab
initio structure solutions applying real space methods with an included close-contact penalty were carried out
for all compounds. The following Rietveld refinements led to excellent wRp-values between 2.5% and 4.1%.
Compounds 1 and 2 crystallise isostructurally in the monoclinic space group P21/c exhibiting a pseudo-biaxial
¯
hydrogen bond motif. 3 crystallises in the triclinic space group P1 with intermolecular head-to-tail hydrogen
Received 16th June 2013,
Accepted 7th August 2013
bonds connecting the molecules to one-dimensional ribbons. Nevertheless, all compounds grow in a sheet-like
morphology with lateral dimensions of several hundred micrometres indicating a fast growth in two dimen-
sions along two of the crystal axes. Since all three molecules possess inversion symmetry cancelling the molec-
ular dipole moment the growth mechanism itself has to be dominantly driven by the formation of hydrogen
bond networks.
DOI: 10.1039/c3ce41158c
www.rsc.org/crystengcomm
Introduction
three-dimensional), however, plays a fundamental role in
order to vary macroscopic properties.
Within the last decades the field of supramolecular chemistry
has attracted significant attention resulting in the synthesis
and design of functional molecules evolving into ordered
superstructures via self-assembly mechanisms. Driven by
non-covalent interactions between the constituent parts,1 like
hydrogen bonding, aromatic π–π stacking, CH–π interactions,
electrostatic or hydrophobic interactions, these complex
structures offer a wide diversity of functions highlighting the
versatility and flexibility within this field of research. The
dimensionality of the resulting nanostructures (from one- to
Certain types of supramolecular building blocks form
predominantly one-dimensional nanostructures. Here,
benzene-1,3,5-tricarboxamides (BTAs) represent an impor-
tant class and are described in detail by Cantekin et al.2 The
choice of appropriate substituents results in a broad range
of materials. For example organogels,3–5 hydrogels,6,7
discotic liquid crystals,8 metal complexation9 and MRI-
contrast agents,10 as well as nucleating agents and clarifiers
for semi-crystalline polymers11–18 have been reported. The
hydrogen bond mediated cooperative effect results in the for-
mation of one-dimensional rod-like nanoobjects. The topo-
logical arrangement of these columnar nanostructures is
dominated by a (pseudo)hexagonal rod packing.19,20 Since
each BTA possesses an intrinsic dipole moment, the build-
up of these rods is strongly connected to the formation of a
macrodipole with a high intrinsic potential energy.21 Only
the macroscopic compensation of these macrodipoles by
neighbouring rods being directed antiparallel and leading to
a Inorganic Chemistry III and Bayreuth Center for Colloids and Interfaces,
University of Bayreuth, 95440, Bayreuth, Germany. E-mail: juergen.senker@uni-
bayreuth.de; Fax: +49 921-55-2788; Tel: +49 921-55-2532
b Macromolecular Chemistry I, Bayreuth Institute of Macromolecular Research
and Bayreuth Center for Colloids and Interfaces, University of Bayreuth, 95440,
Bayreuth, Germany. E-mail: hans-werner.schmidt@uni-bayreuth.de; Fax: +49 921-
55-3206
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3ce41158c
8784
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
elucidation32–35 has proven to be an efficient way to validate
or disprove structure models.
Experimental section
Materials and instruments
All solvents were purified and dried prior to use according to
standard procedures. The starting materials were purchased
from ABCR, Acros, Aldrich, and TCI Europe and used as
received. Elementary analysis (C, H, N) were carried out using a
Vario elementar EL III instrument. Mass spectra were recorded
at RT on a FINNIGAN MAT 112S instrument (70 eV) with elec-
tronic impact ionisation and direct probe inlet. SEM was
performed on a Zeiss 1530 FESEM (3 kV) with a preceding plat-
inum sputtering using a Cressington Sputter Coater 208HR.
Syntheses of 1–3
The general reaction schemes are depicted in Scheme S1
within the ESI.†
Scheme
1
Chemical structures of N,N′-(cyclohexane-trans-1,4-diyl)bis(2,2-
dimethylpropanamide) 1, 1,1′-(cyclohexane-trans-1,4-diyl)bis(3-tert-butylurea) 2 and
N1,N4-bis(tert-butylcarbamoyl)cyclohexane-trans-1,4-dicarboxamide 3 with labelling
of the atoms for the NMR signal assignment.
N,N′-(Cyclohexane-trans-1,4-diyl)bis(2,2-
dimethylpropanamide) 1
Compound 1 was synthesised by dropping pivalic acid chlo-
an antiferroelectric arrangement allows for a fast one-
dimensional growth.
ride (7.3 g, 61 mmol) to
a
mixture of trans-1,4-
diaminocyclohexane (3 g, 26 mmol), pyridine (10 mL), LiCl
(0.05 g) and N-methyl-2-pyrrolidone (NMP, 180 mL) at 0 °C
under nitrogen atmosphere. The reaction mixture was heated
to 80 °C and stirred overnight. The mixture was precipitated
in cold water and the white solid was filtered off, dried under
vacuum for 2 h (70 °C, 100 mbar) and re-crystallised from
methanol. Yield: 4.5 g (16 mmol, 61.5%, based on trans-1,4-
diaminocyclohexane). Anal. calculated for 1: C, 68.04; H,
10.71; N, 9.92. Found: C, 67.34; H, 12.23; N, 9.80%. MS (70 eV),
m/z (%): 282 (M+, 3.3); 197 (10.4); 181 (74.5); 127 (5.7);
102 (100); 85 (9.4); 80 (6.6); 57 (3.8).
Recently, two-dimensional nanostructures with a high
aspect ratio have gained increasing interest22 with lateral
dimensions ranging from a few hundred nanometres up to
the micron scale. Well known inorganic examples are layered
silicates23 and graphene with exceptional properties.24–29
Lately, a new pathway to two-dimensional nanoobjects has
emerged based on supramolecular self-assembly of low-
molecular-mass organic molecules (LMOs).22 Among others,
Zentel and co-workers reported a couple of bis-acylurea
compounds possessing a C5 or C6 alkyl spacer with differ-
ent functional end groups.30,31 An in-depth understanding
of the formation of these nanosheets is still challenging. It
is quite evident that hydrogen bonding is important. How-
ever, the role of dipole moments or even macrodipoles as a
driving force for the two-dimensional growth is still an
open question.
In order to derive a deeper understanding of the struc-
ture–property relations of two-dimensional nanosheets, we
selected three compounds with different hydrogen bond
motifs. The materials (Scheme 1) are based on symmetric
substituted trans-(1,4)-cyclohexane derivatives with increas-
ing number of donor (NH) and acceptor groups (CO),
namely amide 1, urea 2 and acylurea 3 moieties. We focus
on the ab initio structure solutions as well as the hydrogen
bond networks of these three LMOs. Since the lack of suit-
able single crystals prevents using single crystal X-ray dif-
fraction experiments, we employ NMR-crystallographic
strategies to derive both detailed local and topological
features of these compounds. To complement powder dif-
fraction data with solid-state NMR experiments and
computational modeling at various steps of the structure
1,1′-(Cyclohexane-trans-1,4-diyl)bis(3-tert-butylurea) 2
Compound 2 was synthesised by dropping tert-butyl isocyanate
(dissolved in 400 mL THF at room temperature, 5 g, 101 mmol)
to a solution of trans-1,4-diaminocyclohexane in THF (10 g,
44 mmol) at 0 °C under argon atmosphere. The mixture was
stirred overnight at 80 °C, filtered off, dried under vacuum and
re-crystallised from methanol. Yield: 12 g (38 mmol, 87.3%,
based on trans-1,4-diaminocyclohexane). Anal. calculated for 2:
C, 61.5; H, 10.32; N, 17.93. Found: C, 61.17; H, 11.10; N,
17.78%. MS (70 eV), m/z (%): 312 (M+, 9.4); 212 (29.2); 197
(18.8); 139 (7.5); 113 (13.2); 96 (18.8); 68 (9.4); 58 (100); 41 (11.3).
N1,N4-Bis(tert-butylcarbamoyl)cyclohexane-trans-1,4-
dicarboxamide 3
Compound 3 was synthesised by dropping a mixture of
cyclohexane-trans-1,4-dicarbonyl dichloride (3.14 g, 15 mmol)
and 3.65 mL pyridine to a solution of 1-tert-butyl urea (3.49 g,
30 mmol) in THF at 0 °C under argon atmosphere. The reac-
tion mixture was stirred overnight at 70 °C, filtered off, dried
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8785

View Article Online
Paper
CrystEngComm
Table 1 Relevant crystallographic data for 1–3 from PRXD
under vacuum for 2 h at 70 °C and re-crystallised from DMF.
Yield: 2.2 g (6 mmol, 40%, based on cyclohexane-trans-1,4-
dicarbonyl dichloride). Anal. calculated for 3: C, 58.64; H, 8.75;
N, 15.21. Found: C, 58.42; H, 8.81; N, 15.16%. MS (70 eV),
m/z (%): 353 (M+, 91.5); 313 (4.7); 280 (33.9); 254 (15.1); 240 (7.5);
197 (6.6); 169 (14.1); 126 (29.2); 109 (3.7); 81 (17.9); 59 (100).
1
2
3
Formula
C16H30N2O2
282.42
Monoclinic
P21/c
C16H32N4O2
312.45
Monoclinic
P21/c
C18H32N4O4
368.47
Triclinic
M/g mol−1
Crystal system
Space group
¯
P1
a/Å
b/Å
c/Å
α/°
14.183(3)
6.159(1)
9.889(2)
90
15.435(7)
6.762(3)
8.883(4)
90
6.092(3)
7.325(4)
12.473(6)
73.828(3)
83.507(3)
87.597(2)
531.1(8)
0.5/1
1.151(2)
293
0.23(1)
−0.012(4)
0.0025(2)
0.76(3)
Ab initio structure determination with powder X-ray
diffraction
β/°
98.383(1)
90
854.6(8)
0.5/2
1.097(1)
293
96.343(2)
90
921.4(12)
0.5/2
1.125(2)
293
γ/°
PXRD measurements for compounds 1–3 were carried out in
Debye–Scherrer geometry on a STOE StadiP diffractometer,
which was equipped with Cu Kα1 radiation (λ = 1.5406 Å) and
a curved germanium monochromator (oriented according to
the 111 plane). The samples were filled in capillary tubes with
a diameter of 0.5 mm and measured in the 2Θ range of 3–50°
with a step size of 0.015°. The powder diffractograms were
fully handled using the module REFLEX PLUS from the com-
mercial program package Accelrys MS Modeling (version 5.0).36
After indexing, Pawley refinement and space group assign-
ment, the structure solution step was performed by means
of real-space methods using the parallel tempering algo-
rithm. For every structure solution, the molecule was first
geometry optimised using DFT methods (see section Compu-
tational methods). As starting models for compounds 1–3
only half a molecule was set into the asymmetric unit as one
motion group. Besides the possible rotational and transla-
tional degrees of freedom, all sustainable torsion angles
in each molecule fragment were set free during the struc-
ture solution. Additionally, a preferred orientation model
(March–Dollase) was applied during the solution with focus
on the shape of the crystallites (R0) as well as the orienta-
tion of the normal of the crystal faces (a*, b*, c*).37
For the Rietveld refinement, at first four cycles including a
relaxation of atomic parameters, a global isotropic temperature
factor and a preferred orientation correction according to the
Rietveld–Toraya equation38,39 were carried out. By taking into
account energy considerations using the COMPASS force field,40
the molecular structure was maintained without limiting rota-
tional and translational degrees of freedom. The resulting num-
ber of refined structural parameters (see Table 1) is hence not
strictly representative due to the application of the energy
constraint during the refinement. This force field assisted
refinement is based on a combined figure of merit (Rcomb) with
V/Å3
Z′/Z
ρ/g cm−3
T/K
U
V
W
NA
0.20(1)
−0.021(3)
0.0029(2)
0.42(2)
0.001(1)
−0.031(1)
0.223
0.14(1)
0.005(3)
0.0013(2)
0.79(4)
0.002(2)
0.009(1)
0.654
NB
0.00(2)
Zero-point shift
R0
−0.021(1)
a
0.868
a*
b*
c*
0.9877(2)
0.137(1)
0.074(1)
81
−0.9885(3)
0.147(2)
0.030(2)
87
−0.109(5)
−0.087(9)
−0.990(1)
93
0.0157
0.0254
No. ref. struct. par.b
Rp
wRp
0.0272
0.0411
0.0217
0.0301
a
Preferred orientation coefficient of the sample according to the
March–Dollase function representing a dimensionless value
reflecting the shape of the crystallites; R0 < 1 for platelets, R0 > 1 for
needles. b The number of refined structural parameters includes one
isotropic temperature factor and three translational elements of each
atom within the asymmetric unit. Since a COMPASS force field with
an energy constraint was applied, the refinement of the atomic
positions is not handled independently.
default value of 40 kcal mol−1 was used prohibiting the breaking
of covalent bonds during the refinement and thus reducing the
independent number of refined structural parameters markedly.
Afterwards, besides the adjustment of the lattice parame-
ters, the pseudo-Voigt peak profile including FWHM with its
profile parameters NA and NB were optimized. The pseudo-
Voigt peak shape function as a linear combination of a
Gaussian (G) and a Lorentzian (L) includes a Θ-dependent
mixing parameter η whose Θ-dependence is thus given by
ηðΘÞ ¼ ðNA þ NBÞ2Θ
ð3Þ
where NA and NB are adjustable parameters. Besides, the
zero-point shift, sample off-centering, asymmetry correction
(Finger–Cox–Jephcoat)41 and the experimental background
using 20 orthogonal polynomials were refined. For both
refinement steps, 15 evaluations per cycle per degree of free-
dom were performed. Relevant crystallographic data are sum-
marized in Table 1. Atomic parameters, the temperature
factor and the occupancy of 1–3 are included in the CIF files
which are provided in the ESI.†
Rcomb ¼ ð1−wcombÞwRp þ wcombREnergy
ð1Þ
where wcomb represents the energy weighting factor that was set
to 0.5. The energetic contribution, REnergy, to the combined fig-
ure of merit is defined as follows:




E  Emin
Etol
REnergy  tanh 0.1
ð2Þ


Solid-state NMR spectroscopy
where E represents the total energy, Emin the energy in the
global minimum and Etol the energy window above Emin in
which possible structure solutions are tolerated. Here, the
1H and 13C chemical shifts are referenced to TMS
(δref((1H3C)4Si) = 0 ppm, δref((H313C)4Si) = 0 ppm), 15N
8786
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
chemical shifts are reported with respect to nitromethane
Computational methods
(δref(H3C–15NO2) = 0 ppm). The spin rate for all MAS experi-
Before the ab initio structure solutions of compounds 1–3, all
molecules were geometry optimised by DFT methods using
the module DMol3 from the program package Accelrys MS
Modeling (version 5.0).36 Here, the double zeta plus
polarisation basis set with the GGA functional PW91 was
applied.46 The self-consistent field (SCF) energy convergence
was set to 1.0–6 eV per atom.
1
ments was set to 10 000 1 Hz. The 1D H-DUMBO and 2D
1H–1H double-quantum-single-quantum (DQ-SQ) correlation
experiments were performed on a Bruker Avance III spectrome-
ter at a proton resonance frequency of 400 MHz with a 3.2 mm
triple resonance probe. The CP and the HETCOR experiments
on 13C and 15N were performed on a Bruker Avance II spec-
trometer with a proton frequency of 300 MHz using a 4 mm
triple resonance probe. For the latter experiments proton
broadband decoupling was realised with a SPINAL64 sequence
during acquisition. The nutation frequency and pulse length
were set to 72 kHz and 5.6 μs (15N)/6.8 μs (13C), respectively.
Results and discussion
Morphology
Morphological analyses using scanning electron microscopy
(SEM) reveal a two-dimensional growth of compounds 1, 2
and 3. Large platelets possessing a high aspect ratio were
obtained from hot isotropic solutions of butan-2-one with con-
centrations between 50 and 500 ppm depending on their solu-
bility. Bisamide 1 shows platelets with well-defined edges and
a widely homogenous surface (Fig. 1a) whereas bisurea 2
exhibits partly fringed edges but also a homogenous surface
(Fig. 1b). At a first glance the bisacylurea 3 shows sharp edges
and a homogenous surface as well. However, when magnifying
the edge of the platelet, it becomes clear that one platelet
consists of several thin sheets (Fig. 1c). In contrast, no fine
structure can be determined by using SEM in case of 1 and 2.
1
For the H-DUMBO experiments the DUMBO pulse length
and the nutation frequency were adjusted to 30.50 μs and
89.3 kHz, respectively. The total window length between the
DUMBO pulses during acquisition was set to 5.6 μs with a
dead time delay of 1.2 μs before acquiring a point. A
CRAMPS scaling factor of λscaling = 0.5 was determined on
glycine, where all isotropic chemical shifts are well known.42
Subsequently, the shifts of all 1H DUMBO spectra were
corrected accordingly.
In the case of the 1H–1H DQ-SQ correlation experi-
ments, double quantum excitation and reconversion was
achieved through the R2092 sequence43 and high resolution
in both dimensions through a DUMBO sequence.44 For the
R-elements, 90–270° composite pulses were used with 80 μs
excitation/reconversion time (corresponding to 8 R-elements
each) and 100 kHz of nutation frequency. The desired coher-
ences were selected through an eight-fold phase cycling. For
DUMBO in the indirect dimension the window length was set
to 4.6 μs with an increment of three DUMBO cycles, whereas
all remaining parameters for DUMBO in both dimensions
were the same as in the one-dimensional DUMBO experi-
ments. For both the indirect and direct dimension a scaling
factor of λscaling = 0.5 was determined as described above.
The 1D CP spectra of 13C and 15N were recorded using a
ramp on the proton channel and a contact time of 5 ms with
nutation frequencies of 35/45 kHz for 15N/13C. For the
1H–15N/13C HETCOR experiments a DUMBO sequence was
applied in the indirect dimension with a pulse length of
28.8 μs, a nutation frequency of 91 kHz, a delay of 2 μs and
four/three DUMBO cycles as increment. Magnetization transfer
was achieved using the PRESTO-II sequence.45 It ensures that
spin diffusion between the protons during the contact time is
suppressed in contrast to conventional magnetisation transfer
by CP. For all compounds, the transfer time for PRESTO was
set to 178 μs according to 16 R-elements before and after the
90° pulse probing only the closest 1H–13C and 1H–15N dis-
tances. Thus, correlation signals only correspond to covalently
bonded nuclei. The nutation frequency for 1H and 15N/13C dur-
ing PRESTO was set to 90 kHz and 39/70 kHz, while the FID
was recorded after a spin echo for refocusing the chemical shift
interaction. The refocusing period was chosen to one/two rotor
periods for 15N/13C, respectively. An eight-fold phase cycling
allowed the selection of the desired coherences.
Structural information obtained from solid-state NMR
spectroscopy
Compounds 1–3 form only microcrystalline powders
preventing structure analysis by single crystal X-ray diffraction.
Since this circumstance is not specific for our samples but a
common case for organic substances, the development of
alternative structure elucidation methods for powder samples
is necessary. Ab initio structure solutions employing solely
PXRD data are often hampered by a severe loss of information.
Symmetry equivalent reflexes always coincide and higher order
reflexes overlap heavily, reducing the number of independent
intensity information.47 While topological information might
still be obtained with reasonable accuracy, local structural
details are strongly affected.34,47 In this context, solid-state
NMR spectroscopy provides complementary data and thus
evolved into an important element of NMR crystallographic
strategies. Meanwhile, solid-state NMR is able to participate in
nearly all steps of the structure solution process starting from
space group selection, over model building up to the final
Rietveld refinement.19,47–50 Symmetry information including
the content of the asymmetric unit might be obtained by
deriving Wyckoff spectra48,51 from high-resolution experiments
and by determining rotational symmetry elements47,52,53 based
on orientation correlations of CSA tensors of neighbouring
nuclei. Analysing hetero- and homonuclear connectivities,
distances, distance sums and even torsion angles measured by
1D and 2D dipolar recoupling experiments support the
construction of structure models.19,20,32–34,49,50 The expressive-
ness of such measurements is significantly increased by
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8787

View Article Online
Paper
CrystEngComm
Fig. 1 SEM images of two-dimensional structures of (a) bisamide 1 (500 ppm), (b)
bisurea 2 (200 ppm) and (c) bisacylurea 3 (50 ppm) formed in butan-2-one. The regions
where the magnified images (insets) have been collected are marked using white boxes.
Fig. 2 1D MAS spectra at νMAS = 10 kHz for compounds 1 (black), 2 (red) and 3
(blue): (a) 1H-DUMBO (B0 = 9.4 T); the strong signal of the methyl groups is
truncated to highlight the weaker resonances, in particular the NH signals; (b) 13C
CP-MAS (B0 = 7.04 T); (c) 15N CP-MAS (B0 = 7.04 T). For the CRAMPS experiments
the chemical shifts are corrected according to glycine (λscaling = 0.5).
combination with quantum chemical calculations.54,55 For
instance, hydrogen bond scenarios can be probed by combin-
ing ab initio chemical shift calculations and high-resolution
NMR measurements.34,54,56 Even the substructure of light
atoms like hydrogen has successfully been determined.32,50
Since most of these methods require high resolution spectra,
hetero- and homonuclear decoupling of strongly coupled spin
systems like protons is necessary. Moreover, for a correct inter-
pretation of these spectra, a complete assignment of all signals
is essential, which can be obtained through 2D heteronuclear
correlation experiments.
Following this strategy, information about hydrogen bond
patterns, configurations and symmetries of the crystal struc-
tures of compounds 1–3 are deduced. In particular, we
support the ab initio structure solutions by PXRD through
solid-state NMR experiments on the three NMR-active nuclei
8788
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
Fig. 3 (a) 1H–13C-HETCOR and (b) 1H–15N-HETCOR spectrum of compound 3, at B0 = 7.04 T and νMAS = 10 kHz. The 1H chemical shifts in the f1 domains are corrected
according to glycine (λscaling = 0.5). The transfer time was set to 178 μs visualising only directly bonded protons.
1H, 13C and 15N. First, a complete assignment of 1D high-
resolution spectra of 1H, 13C, 15N experiments through 2D
1H–13C and 1H–15N HETCOR spectra is conducted. Fig. 2
assigned to the quaternary carbon atom of the tert-butyl
group while the two remaining signals at δ = 155.3 ppm and
177.2 ppm belong to the CO groups. A comparison of their
line shapes observed at different magnetic fields of 7.1 T and
9.4 T, respectively, reveals an inverse dependence of the split-
ting on the field strength. This line shape is, therefore, caused
by second order quadrupolar interaction between the
neighbouring 14N nucleus and the 13C spins.57 This was also
reproduced by simulations of 1D spectra for a 13C–14N spin
pair with the program WSOLIDS1 (see Fig. S2b in the ESI†).20,58
To assign the remaining peaks in the 1H-DUMBO at δ =
8.0 ppm, 8.6 ppm and 11.2 ppm, 1H–15N HETCOR experi-
ments were performed (Fig. 3b). The 15N CP spectrum of
3 (Fig. 2c) reveals two different peaks at δ = −237.2 ppm and
−261.0 ppm. Here, the 15N site at δ = −261.0 ppm shows cor-
relations with a single proton signal at δ = 8.4 ppm. Since
already the carbon atoms directly bound to a nitrogen atom
were influenced through second order quadrupolar interac-
tion, a single-pulse experiment under MAS at a higher mag-
netic field strength and a line shape simulation using
WSOLIDS1 were conducted (Fig. S1and Table S1 in the
ESI†).58 It becomes clear that the two peaks at δ = 8.0 and
8.6 ppm correspond to a single proton with an isotropic shift
of δ = 8.4 ppm. This effect is well-known for NH groups.57
The remaining 15N signal at δ = −237.2 ppm shows only one
correlation in the 1H–15N HETCOR to the proton signal at
δ = 11.2 ppm and thus corresponds to the second NH group.
In order to assign the two carbonyl and the two NH sig-
nals to the corresponding chemical units, the experimental
resonances were compared to chemical shifts in solution-
state NMR, being calculated based on an increment system
according to ref. 58 (see Table S2 in the ESI†).59 Here, the car-
bon groups C4 and C6 of the acylurea group which are
1
depicts high-resolution 1D spectra of H, 13C and 15N for all
three compounds. The assignment will be done exemplarily
for compound 3, since the procedure for the remaining
samples is almost identical. The 2D 1H–13C-HETCOR and
1H–15N-HETCOR experiments for that purpose are pictured
in Fig. 3a and 3b.
The 1H-DUMBO spectrum of 3 shows a sharp, intense peak
at δ = 1.3 ppm (Fig. 2a). This signal couples in the 1H–13C-
HETCOR to a carbon signal at δ = 29.9 ppm (Fig. 3a). Both the
13C and 1H shifts are indicative for CH3 groups. Moreover, the
sharpness and high intensity of both peaks are characteristic
for CH3 for the following reasons: first, the well-known rota-
tion of the groups around the C–CH3 bond truncates dipolar
coupling to other spins, which raises the transversal relaxa-
tion time and thus reduces the width of the peaks for both
spins. Second, the high abundance of CH3 protons increases
their signals in DUMBO as well as in 13C CP. The carbon
signals at δ = 30.6 ppm and – remarkably shielded – at δ =
26.6 ppm correspond to the two different sets of CH2
groups within the cyclohexane ring, one carbon signal with
couplings to the resolved proton shifts at δ = 0.4 and
1.6 ppm, the other one with two overlapping proton signals
at ca. δ = 0.8 and 1.3 ppm. The CH unit of the ring is assigned
to the more deshielded peak at δ = 1.6 ppm for 1H, coupling to
the carbon signal at δ = 45.0 ppm, since both carbon and pro-
ton shifts are typical for CH groups. The remaining signals in
the 13C CP (Fig. 2b, δ = 51.2 ppm, 155.3 ppm and 177.2 ppm)
do not give rise to cross correlation peaks in the 1H–13C-
HETCOR and are thus not covalently bonded to protons. The
peak at δ = 51.2 ppm in the 13C CP spectrum is unequivocally
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8789

View Article Online
Paper
CrystEngComm
Table 2 Chemical shifts in ppm for all 1H, 13C and 15N of compounds 1–3
(for labelling see Scheme 1). The asterisks indicate average shifts for cases
where the corresponding signals show a splitting due to second order
quadrupolar interaction with 14N. All spectra used for assignment of 1 and 2
are contained in the ESI† (Fig. S3 and S4)
and 2. The corresponding values for the chemical shifts are
summarized in Table 2.
The 1D CP spectra of 15N show only one NH peak for com-
pound 1 and two peaks for 2 and 3. The molecular structures,
however, exhibit two nitrogen atoms in the case of 1 and four
in the case of 2 and 3. The same comparison applies for the
1D CP spectra of 13C and the 1H-DUMBO, where the struc-
tures always show twice the number of groups than the num-
ber of observed resonances. Thus, the asymmetric unit
contains just half a molecule and, therefore, both molecular
and space group symmetry include a two-fold axis or an
inversion centre. The number of possible space groups for
structure solutions is thus reduced which will be discussed at
a later point.
Atom
1
2
3
Unit
C1
C2
C4
C6
C7
C8
C9
N3
N5
H1
H3
H5
H7
H8
H9
29.5
39.0
178.2*
—
48.7*
32.3
33.7
—
32.4
29.9
CH3
Cq
CO
CO
CH
CH2
CH2
NH
NH
CH3
NH
NH
CH
50.0*
159.2*
—
47.2*
34.2
51.2*
155.3*
177.2*
45.0
26.6
30.6
−261.0
−237.2
1.3
8.4*
11.2
36.7
−280.6
−276.4
1.3
6.0*
6.1*
3.3
0.5/1.0
1.0/1.5
−255.2
1.1
—
7.4*
3.5
1.4
1.0
In order to gain information about spatial proximities of
NH protons and thus also possible hydrogen bond patterns
of the molecules, we used 1H–1H DQ-SQ correlation experi-
ments. The NH regions of these spectra are exemplarily
depicted in Fig. 4 for compound 2 and 3 (for compound 1
see Fig. S5 in the ESI†).
For compound 2, both peaks around δ = 5.4 ppm and
6.4 ppm correspond to two overlapping NH signals of the
urea unit with isotropic shifts of δ = 6.0 ppm and 6.1 ppm
(extracted from 1H–15N HETCOR, see Fig. S4 in the ESI†),
both split by the neighbouring 14N (see Table 2). Besides
correlations of the NH protons to the aliphatic region (see
Fig. S6 in the ESI†), correlations of the NH signals among
themselves between δ = 10.8 ppm and 12.8 ppm in the
double-quantum dimension are observed. Since the line
shapes are affected by the 14N nuclei, we cannot distinguish
between cross correlations and autocorrelations. However,
both cases indicate spatial proximity of NH protons to other
1.6
0.8/1.3
0.4/1.6
CH2
CH2
connected to the tert-butyl unit and the cyclohexane ring,
respectively, show a shift of δ = 155.7 ppm and δ = 179.4 ppm,
which is close to the observed shifts of δ = 155.3 ppm and
177.2 ppm in the solids. In the case of 15N, for the two nitro-
gen atoms N3 and N5 shifts of δ = −277.2 ppm and −246.0 ppm
are predicted, whereas the observed shifts are δ = −261.0 ppm
and −237.2 ppm. Considering that the solid-state shifts of 15N
in NH groups are usually influenced more strongly by e.g.
hydrogen bonds than in the case of 13C, the predicted values
show a sufficient agreement with the observed ones.
Thus, all signals in the 1D 1H, 13C and 15N spectra have
unequivocally been assigned to the molecular units of com-
pound 3. This procedure was also applied to compounds 1
Fig. 4 1H–1H DQ-SQ correlation spectra of (a) compound 2 and (b) compound 3 at B0 = 9.4 T and νMAS = 10 kHz. The excitation and reconversion time was set to 80 μs in
both cases for which only the shortest distance correlations are observed. Both chemical shifts of f1 and f2 are corrected according to glycine (λscaling = 0.5). Here, the region
around the NH protons is shown (the whole spectra are depicted in Fig. S6 and S7 in the ESI†).
8790
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
real-space methods using the combination of a close-contact
penalty and wRp, respectively, as cost functions. All molecules
were DFT geometry optimised before performing the structure
solutions revealing in all cases a chair conformation of the
cyclohexane ring as well as Ci symmetry which is energetically
favoured over the also previously discussed C2 symmetry. The
inversion centre is thereby positioned in the centre of gravity of
the cyclohexane ring. In accordance to the 1H–1H DQ-SQ experi-
ments the trans–cis–trans configuration of the acylurea unit in
compound 3 revealed the lowest energy during DFT optimisation.
C16H30N2O2 1 and C16H32N4O2 2. The indexing of the
powder patterns lead unequivocally to a monoclinic metric in
both cases and could subsequently be refined in P2 using the
Pawley algorithm. Assuming that all non-hydrogen atoms
within these compounds possess a volume of roughly 18 Å3,
the molecular volumes can be estimated to 360 Å3 and 396 Å3,
respectively. This size restriction just allows for two molecules
within the unit cell at maximum. The reflection conditions do
not provide reasonable results for any of the five C-centred
space groups but, nevertheless, all remaining 8 primitive ones
might be possible. However, based on the symmetry consider-
ations obtained by 1D 15N and 13C solid-state NMR (compare
Fig. 3b and 3c) whereupon only half a molecule is located in
the asymmetric unit, all possible space groups with the multi-
plicity of 2 on general positions (P2, P21, Pm and Pc) – then
leading to only one molecule in the unit cell – could be
excluded. Therefore, only four space groups (P2/m, P21/m, P2/c
and P21/c) remained and, taking into account the reflection
conditions, P21/c fitted the experimental powder pattern best.
The structure solutions with subsequent Rietveld refine-
ment reveal that 1 and 2 are isostructural and crystallise in
the monoclinic space group P21/c (for crystallographic infor-
mation: see Table 1 in the experimental details section). Rep-
resentative for both compounds, the Rietveld profile plot for 1
is depicted in Fig. 5 (the Rietveld profile plot for 2 is
visualised in Fig. S8 in the ESI†). The a-axis of 2 is roughly
1.2 Å longer than for 1 while the c-axis is shortened by ca.
1 Å. The monoclinic angle is slightly reduced by 2° resulting in
an increased cell volume of about 65 Å3 which perfectly agrees
with the volume requirement of two additional NH groups.
Fig. 6 shows the molecular crystal structure as well as
extended packing plots of N,N′-(cyclohexane-trans-1,4-
diyl)bis(2,2-dimethylpropanamide) 1. Here, the cyclohexane
ring exists in the low-energy chair conformation while the
(1,4)-amide linkage exhibits trans-configuration on the ter-
tiary carbon atom in the ring as synthesised. The internal
H4N4C4O4 torsion angle within the molecule picturing the
amide bond is 179.5° which is close to 180° as expected for
an amide function (see Fig. 6a) leading to almost coplanarity
caused by the inversion symmetry of the molecule itself.
The bisamide compound is characterised by an extended 2D
hydrogen bond network. Due to the internal Ci symmetry, only
one NH⋯O length of 2.11 Å is observed. The corresponding
N⋯O distance amounts to 3.1 Å while the NH⋯O angle of
almost 167° is only slightly below the ideal value of 180° demon-
strating medium-strong hydrogen bonds. The trans-configuration
Fig. 5 Rietveld profile plot of the powder X-ray diffraction pattern of 1 for the
solution in space group P21/c collected at room temperature in the 2Θ range 3–50°.
The section of the 2Θ range of 35–50° shows that even at high 2Θ values the simu-
lation fits excellently to the experimental powder pattern.
NH protons. Since the NH units in urea groups usually favour
a trans–trans configuration each with the connected carbonyl
group (e.g. as depicted in Scheme 1 for compound 2) due to
energetic reasons, typical H–H distances for this configura-
tion score around 2 Å.60 Strong DQ coherences as detected in
Fig. 4a for 2 are thus characteristic for such short distance.
In contrast, for compound 3 only one weak autocorrelation
signal is observed for the NH proton H5 (δ(SQ/DQ)
=
11.4 ppm/22.8 ppm). First, this clearly indicates a spatial
proximity between H5 protons of the inner NH groups. This is
only possible when neighbouring molecules are arranged in a
hydrogen bond pattern. Second, for the NH signal of proton
H3 at δ = 8.4 ppm no self-correlation signal is observed (δ(DQ,
theo) = 16.8 ppm) and thus the intermolecular distances of H3
protons have to be much longer compared to the ones of H5.
Additionally, no correlation between H3 and H5 was detected
either (δ(DQ,theo) = 19.9 ppm). This implies a long inter-
molecular distance between those NH protons of the same
acylurea unit (d > 2 Å) and thus allows determining the molec-
ular configuration. In compound 3 just an additional CO
group is inserted compared to 2 (acylurea compared to urea
unit). For an all-trans configuration of the acylurea group again
a distance around 2 Å between H3 and H5 and, therefore, an
intense DQ correlation signal similar to Fig. 4a is expected.
However, a trans–cis–trans configuration leads to a distance of
more than 3.5
Å rendering the H3–H5 DQ correlation
unobservable under the chosen experimental conditions. The
resulting spatial proximity between the oxygen atom of the
inner CO group and the NH proton H3 favours the formation
of an intramolecular hydrogen bond which might stabilise this
configuration. The encapsulation of H3 in this intramolecular
hydrogen bond might also explain the absence of any autocor-
relation signal. These results indicate a pair-like arrangement
of the molecules within the crystal structure.
Structural information obtained by powder X-ray diffraction
The crystal structures for 1–3 were all obtained by ab initio
structure solutions based on powder X-ray diffraction applying
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8791

View Article Online
Paper
CrystEngComm
Fig. 6 Molecular structure and extended crystal packing plots of compound 1 with hydrogen bonds highlighted in green dashed lines. (a) Molecular structure of 1
represented with all four hydrogen bond interactions with labelling of the amide function as performed in Scheme 1. (b) Section of the crystal structure viewing along the
c-axis. The dashed yellow lines represent the opening angle of the molecules main axes projected into the ab-plane of the crystal. (c) Cutout of the structure presented in
panel b (black dashed circle) showing that one molecule (grey cyclohexane carbon atoms) is enclosed by four molecules (black cyclohexane carbon atoms), two below and
two above. This cutout is rotated by 5° along the b-axis. (d) Packing plot showing that every molecule builds hydrogen bonds to four neighbouring molecules in one direction.
This packing plot is obtained by −90° rotation along the a-axis followed by a −35° rotation along the b-axis as presented in panel c. All hydrogen atoms except the nitrogen-
bonded ones have been omitted in (b)–(d) for clarity.
of the amide functions hence guarantees the formation of two
H-bond strands in one direction which is schematically
depicted in Fig. 6a.
of almost 167°. So, the oxygen atom of the carbonyl group is
shifted slightly out of the planar H3N3C4N5H5-plane in order
to form a hydrogen bond network properly. Since one urea
group possesses two NH-donor groups, two different H-bond
lengths might be observed. Nevertheless, the two bonds are
almost equal with bond lengths of 2.19 Å and 2.23 Å, which
is consistent with the results extracted from the 1H and 15N
chemical shifts (compare Fig. 2a and 2b), while the corre-
sponding N⋯O distances result in 3.13 Å and 3.17 Å. All
these distances are slightly longer than found for the
bisamide 1. This tendency is also true for the related NH⋯O
angles which are 154.2° and 153.5°. Therefore, the hydrogen
bonds for the bisurea are supposed to be weaker than the
ones obtained for the bisamide. However, the H-bond pattern
obtained for 2 is more complex than for 1 due to the addi-
tional NH group. Compared to 1, the urea group undertakes
the same role as the amide function. Therefore, one acceptor
carbonyl group is connected to two NH-donor groups and
vice versa so that one molecule is H-bond connected to four
neighbouring molecules, too (see Fig. 7c and 7d).
This is, for example, in contrast to other bisurea com-
pounds where each molecule is hydrogen-bonded to only two
other molecules placed below and above it to self-assemble
into 1D fibrillar aggregates.60,61 Nevertheless, the nature of
the urea group itself enables the molecules to form again two
H-bond strands as already observed for compound 1. The
propagation direction can also be described as parallel to the
c-axis of the crystal, so a comparable fast growth in this direc-
tion is obtained. Moreover, since also an opening angle
The propagating direction of the H-bond strands is thereby
aligned parallel to the c-axis of the crystal leading to a fast
growth along this crystal axis. A closer look on the packing
motif reveals two additional important features. First, both
molecules within the unit cell are twisted towards each other.
When assuming a straight line along the main axis of each
molecule propagating through the quaternary carbon atoms of
the t-butyl group followed by a projection into the ab-plane of
the crystal, an opening angle of 60° is obtained (see Fig. 6b,
yellow dashed lines). Second, each amide function within one
molecule (NH/CO as donor/acceptor) is connected to one
independent counterpart within another molecule. So, every
molecule is attached to four neighbouring molecules (see
Fig. 6c and 6d) where one donor group interacts with one
acceptor group (and vice versa). Due to the twist of the mole-
cules, however, a second ‘indirect’ propagation direction along
the b-axis that also possesses the tendency of growing fast is
observed. Since along the crystals' a-axis only van der Waals
interactions seem to play the major role – the shortest proton–
proton distance being obtained along this crystal axis amounts
to 2.44 Å – the corresponding rate of growth is much smaller
compared to the growth along the b- and c-axis, respectively.
Analogous results are obtained for the bisurea compound
2 with an identical molecular geometry as observed for 1 (see
Fig. 7a). Nevertheless, the urea group is not perfectly planar
with corresponding torsion angles (H3N3C4O4 and H5N5C4O4)
8792
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
Fig. 7 Molecular structure and extended crystal packing plots of compound 2 with hydrogen bonds highlighted in green dashed lines. (a) Molecular structure of 2
represented with all eight hydrogen bond interactions with labelling of the amide function as performed in Scheme 1. (b) Section of the crystal structure viewing along the
c-axis. The dashed yellow lines represent the opening angle of the molecules main axes projected into the ab-plane of the crystal. (c) Cutout of the structure presented in
panel b (black dashed circle) showing that one molecule (grey cyclohexane carbon atoms) is enclosed by four molecules (black cyclohexane carbon atoms), two below and
two above. This cutout is rotated by 5° along the b-axis. (d) Packing plot showing that every molecule builds hydrogen bonds to four neighbouring molecules in one direction.
This packing plot is obtained by −90° rotation along the a-axis followed by a −25° rotation along the b-axis as presented in panel c. All hydrogen atoms except the nitrogen-
bonded ones have been omitted in (b)–(d) for clarity.
between the two twisted molecules within the unit cell of 68°
is observed (see Fig. 7b, yellow dashed lines), a second fast
growth direction along the b-axis is ensured. The discrepancy
of 8° is based on the increased length of the bisurea mole-
cule with its accompanying H-bond capabilities that need a
broadening of this angle to achieve a sufficient donor–accep-
tor interaction. Due to the van der Waals forces as the domi-
nating interaction along the crystals' a-axis – as already
observed for 1 – a fast growth in this direction is inhibited.
Here, the shortest intermolecular proton–proton distance
with 2.46 Å is thereby identical as obtained for the bisamide.
C18H32N4O4 3. The indexing of the powder pattern of
compound 3 revealed a triclinic metric that was successfully
refined in P1 using the Pawley algorithm. Based on the symmetry
information obtained by the 1D 15N and 13C spectra
(Fig. 2b and 2c), respectively, where the content of the
twisted towards the cyclohexane ring with a torsion angle
(H7C7C6O6) of almost 133°. This alignment far beyond the
ideal 180° might explain the significant shielding of the CH2
group with a chemical shift of δ = 26.6 ppm obtained in the
13C CP spectrum (see Fig. 2b) and, moreover, can guarantee
the formation of an H-bond network which will be discussed
1
later. As already confirmed by H–1H DQ-SQ solid-state NMR
(see Fig. 4, right side) and strongly supported by the DFT
geometry optimisation, the acylurea unit possesses a trans–
cis–trans configuration (Fig. 8a). Here, an intrinsic (1,6)-
hydrogen bond with a length of 1.96 Å forming a stable
six-membered ring is built. The corresponding N⋯O distance
as well as the NH⋯O angle are 2.69 Å and 126°.
In 2007, Davis et al. reported the structure of a similar
bisacylurea compound obtained by single crystal X-ray dif-
fraction where an aliphatic pentyl group was chosen as a
linker between the acylurea groups (BUC5BU).31 Here, the
molecule possesses an intrinsic C2 symmetry with the same
configuration of the acylurea group as observed for our mole-
cule. The two-fold axis thereby propagates directly through
the middle carbon atom of the C5 linking unit.
Beyond that, the cis HNCO units forming the intramolecu-
lar hydrogen bond point in the same direction as in contrast
to the Ci symmetric compound 3 (see Fig. 8b). However, the
intramolecular H-bond distance of 2.09 Å and the corresponding
N⋯O distance of 2.74 Å is longer than observed for the cyclohex-
ane derivative while, surprisingly, the NH⋯O angle (128.6°)
is larger. When comparing the planarity, it becomes obvious
that the acylurea group of the BUC5BU compound is slightly
out of plane with torsion angles of 169.9° (H5N5C6O6, trans),
¯
asymmetric unit was limited to half a molecule, P1 was
considered to be the correct space group. Therefore, 3 crystallises
¯
in P1 with crystallographic data summarised in Table 1.
The Rietveld profile plot is depicted in Fig. S9 in the ESI.†
The unit cell consists of one Ci-symmetric molecule
based on only half a crystallographic independent molecule
in the asymmetric unit. The molecule itself possesses simi-
lar structural behaviour as already obtained for compounds
1 and 2 (chair conformation of the cyclohexane ring, see
Fig. 8a). The acylurea unit itself is perfectly planar with
amide torsion angles of 178.8° (H3N3C4O4 and H5N5C6O6,
both trans-configured) and 0.8° (H5N5C4O4, cis-configured)
respectively, leading to a perfect coplanarity (see Fig. 8a). Fur-
thermore, the directly bonded non-urea carboxylic group is
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8793

View Article Online
Paper
CrystEngComm
Fig. 8 Molecular structures of compound 3 (a) and BUC5BU31 (b) represented with intra- and intermolecular hydrogen bonds (dashed pink and green lines, respectively) with label-
ling of the acylurea units as performed in Scheme 1. (c) Section of the crystal structure of 3 viewed along the a-axis. The dashed green lines represent the intermolecular hydrogen
bonds to two neighbouring molecules parallel to the crystals' c-axis. (d) Section of the crystal structure of 3 viewed along the c-axis. This packing plot is obtained by 100° rotation
along the a-axis, followed by a small rotation (−10°) along the b-axis. All hydrogen atoms except the nitrogen-bonded ones have been omitted in (c) and (d) for clarity.
3.9° (H5N5C4O4, cis) and 180° (H3N3C4O4, trans), respectively,
analogous to the angles obtained for 3. But, moreover, the
acylurea moieties of the molecule do show a non-coplanarity
with a mutual interplanar angle of 43.3°.
agreement with the chemical shift of roughly δ = 11.4 ppm
for this NH-proton obtained in the 1D 1H solid-state NMR
spectrum (see Table 2). This fact is, furthermore, corrobo-
rated by the NH⋯O angle of 174° which is very close to the
ideal 180°. The direction of the intermolecular hydrogen
bonds is therefore parallel to the c-axis of the crystal. Since
only three molecules are involved in this pattern, the self-
assembly can – per definition – only be described as classi-
cal monoaxial. Though, the self-assembly direction is
established by stepwise adding of new molecules along the
crystals' b-axis via hydrogen bonds and, therefore, the fast
growth is also observed along this axis. Nevertheless, since
the molecules themselves are twisted by almost 45° com-
pared to both the H-bond direction (c-axis) as well as the
growth direction (b-axis), a two-dimensional morphology as
observed in SEM can still be obtained (see Fig. 8d).
The crystal structure of 3 is schematically pictured in
Fig. 8c and 8d. According to the H-bond pattern, it is worth
mentioning that only the cis-configured amide functions partic-
ipate in two intermolecular hydrogen bonds each forming in
principle one intermolecular six-membered ring (similar to
the one already observed in case of the intramolecular
H-bond). Interestingly, the corresponding counterpart within
a neighbouring molecule also belongs to the cis-configured
amide function (see Scheme 2a). The number of neighbouring
molecules for each molecule therefore is two, which is in
contrast to the ones obtained for the compounds 1 and 2. This
alignment in pairs could already be validated by 1H–1H DQ-SQ
solid-state NMR experiments (see Fig. 4). While no cross corre-
lation signal between the two different NH-protons (H3 and
H5) was observed since the proton–proton distance of ∼3.6 Å
is too long, an auto correlation signal for the NH-protons H5
was found (d(H5–H5 = 2.5 Å). In case of the BUC5BU com-
pound from ref. 31, however, a similar 1H–1H DQ-SQ spectrum
as obtained for compound 2 could be expected (compare
Fig. 4a), since an intermolecular H3–H5 distance of ∼3 Å
might still be detectable within the applied excitation time.
However, an extensive 2D hydrogen bond pattern – as
observed for 1 and 2 – is impossible to realise due to this
intermolecular cis-arrangement of the amide functions (com-
pare Scheme 2a). Nevertheless, the obtained H-bond of 1.75 Å
is very short with an N⋯O distance of 2.75 Å and, there-
fore, has to be categorised as strong which is in very good
Scheme 2 Donor–acceptor interactions observed for (a) compound 3 forming one
intra- and two intermolecular hydrogen bonds per half molecule and (b) BUC5BU
forming one intra- and four intermolecular hydrogen bonds per half molecule. The
black dashed lines represent the hydrogen bonds between the NH- and CO-groups.
8794
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
In comparison, the BUC5BU structure presented in ref. 31
shows a different hydrogen bond pattern. It is evident that the
cis-configured amide function (O4C4N5H5) builds inter-
molecular hydrogen bonds, but they are not connected to other
cis-configured amide functions but rather with the appropriate
donor/acceptor counterpart that also forms the intramolecular
H-bond (see Scheme 2b). So, in principle every molecule is
involved in four six-membered rings, two intramolecular and
four intermolecular ones. Here, the correspondent hydrogen
bond lengths result in 2.11 Å and 2.16 Å, respectively, while the
N⋯O distances of 2.88 Å and 2.99 Å are much longer than
observed for the cyclohexane derivative 3. Interestingly, the par-
ticular NH⋯O angles are 135° and 159°, respectively,
suggesting that the intermolecular H-bonds for our bisacylurea
compound are much stronger than observed for BUC5BU. Nev-
ertheless, the compound investigated by Davis et al. possesses
a classic biaxial hydrogen bond system where each BUC5BU
molecule is hydrogen-bonded to four adjacent molecules as
already described for 1 and 2. This, however, might be caused
due to the intrinsic molecular C2 symmetry while a centrosym-
metric molecular symmetry (compound 3) leads only to a clas-
sical monoaxial hydrogen bond system.
similar benzene-based compound62 no connection to a fast
two-dimensional growth was made. This arrangement is an
alternative to the classical variant where the hydrogen bond
strands are crossed instead of the molecules. In compound 3
¯
(crystallising in P1), on the other hand, each molecule forms
H-bonds to two adjacent molecules, leading to a one-
dimensional ribbon-like structure per definition. It is remark-
able that this compound still shows a sheet-like morphology.
This might be caused by the special arrangement of the mol-
ecules in the packing with respect to the crystal axes.
An important aspect with respect to the growth process of
the sheets deals with the role of dipole moments for the
growth mechanism. For the growth of one-dimensional rod
like nanostructures – e.g. cyclohexane- or benzenetrisamides –
it is known that dipole forces play an important role.21 Here,
every molecule possesses an intrinsic dipole moment. Within
one rod, this dipole moment strongly increases and so-called
macrodipoles are generated. In order to obtain an anti-
ferroelectric crystal being energetically favoured, all macro-
dipoles must be compensated by an antiparallel arrangement
of themselves.63 The net dipole moment of zero is thereby
achieved during the crystallisation process. This argument is
also valid for the BUC5BU compound investigated in ref. 31.
Even if a two-dimensional self-assembly is achieved, the intrin-
sic C2 symmetry of the molecules implies an intrinsic dipole
moment, too, which is only compensated due to the space
group symmetry during crystallisation as well. In contrast, for
the two-dimensional sheet like nanostructures presented here,
dipole forces or even macrodipoles do not play a major role.
The dipole moment is already cancelled in each molecule due
to the inversion symmetry of the molecules themselves. So, the
fast growth of the nanostructures in two directions (1 and 2)
(or one direction for compound 3, respectively) giving two-
dimensional nanosheets is, therefore, mainly induced by the
hydrogen bond mediated donor–acceptor interactions between
the appropriate molecular counterparts.
Conclusion
In summary, three cyclohexane-based compounds with differ-
ent hydrogen bond motifs were characterised by scanning elec-
tron microscopy, solid-state NMR, PXRD and computational
methods based on DFT. SEM measurements revealed sheet-like
morphologies for all three compounds with lateral dimensions
of several hundred micrometres with substantial aspect ratios.
The crystal structures of those compounds were elucidated by
means of NMR-crystallographic strategies. Based on an
unequivocal signal assignment of the 1D spectra by performing
1H–13C- and 1H–15N HETCOR experiments also considering the
1H/14N- and 13C/14N second-order quadrupolar interaction we
were able to restrict the space group symmetry and to deter-
mine the content of the asymmetric unit. The evaluation of
1H–1H DQ-SQ spectra revealed spatial proton–proton connectiv-
ities of the NH groups for all compounds. Additionally for
compound 3, they allowed probing both the molecular configu-
ration such as the existence of the intramolecular hydrogen
bond and the local environment like the H-bond pattern
leading to a pair-like molecular arrangement. This information
was crucial to make the ab initio structure solutions by real-
space methods more efficient and remove ambiguities.
Compounds 1 and 2 crystallise in P21/c and their crystal
structures exhibit an interesting “pseudo-biaxial” hydrogen
bond system where each molecule is directly connected to
four neighbouring molecules via moderate H-bonds. Caused
by the crossed alignment of the molecules within the unit
cell (see Fig. 6d and 7d), the H-bond mediated strands are
growing fast in two directions even though both H-bond
strands are parallel, while the growth in the third dimension
is retarded resulting in two-dimensional nanosheets.
Although such a structural motif was also observed for one
Acknowledgements
The authors want to thank the DFG (SFB 840, Project B4) for
funding this work, Anna-Maria Dietel for performing the
elementary analysis and Dr. Wolfgang Milius for the adjuvant
discussions with respect to crystallographic issues.
References
1 J.-M. Lehn, Angew. Chem., Int. Ed. Engl., 1990, 29, 1304.
2 S. Cantekin, T. F. A. de Greef and A. R. A. Palmans, Chem.
Soc. Rev., 2012, 41, 6125.
3 Y. Yasuda, E. Iishi, H. Inada and Y. Shirota, Chem. Lett.,
1996, 575.
4 K. Hanabusa, C. Koto, M. Kimura, H. Shirai and A. Kakehi,
Chem. Lett., 1997, 429.
5 J. J. van Gorp, J. A. J. M. Vekemans and E. W. Meijer, J. Am.
Chem. Soc., 2002, 124, 14759.
This journal is © The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 8784–8796 | 8795

View Article Online
Paper
CrystEngComm
6 N. Shi, H. Dong, G. Yin, Z. Xu and S. Li, Adv. Funct. Mater.,
2007, 17, 1837.
7 A. Bernet, R. Q. Albuquerque, M. Behr, S. T. Hoffmann and
H.-W. Schmidt, Soft Matter, 2012, 8, 66.
8 Y. Matsunaga, N. Miyajima, Y. Nakayasu, S. Sakai and
M. Yonenaga, Bull. Chem. Soc. Jpn., 1988, 61, 207.
9 M. Gelinsky, R. Vogler and H. Vahrenkamp, Inorg. Chem.,
2002, 41, 2560.
10 P. Besenius, J. L. M. Heynens, R. Straathof,
M. M. L. Nieuwenhuizen, P. H. H. Bomans, E. Terreno,
S. Aime, G. J. Strijkers, K. Nicolay and E. W. Meijer, Contrast
Media Mol. Imaging, 2012, 7, 356.
11 M. Blomenhofer, S. Ganzleben, D. Hanft, H.-W. Schmidt,
M. Kristiansen, P. Smith, K. Stoll, D. Maeder and
K. Hoffmann, Macromolecules, 2005, 38, 3688.
12 P. M. Kristiansen, A. Gress, P. Smith, D. Hanft and
H.-W. Schmidt, Polymer, 2006, 47, 249.
13 F. Abraham, S. Ganzleben, D. Hanft, P. Smith and
H.-W. Schmidt, Macromol. Chem. Phys., 2010, 211, 171.
14 J. Wang, Q. Dou, X. Chen and D. Li, J. Polym. Sci., Part B:
Polym. Phys., 2008, 46, 1067.
32 L. Seyfarth, J. Seyfarth, B. V. Lotsch, W. Schnick and
J. Senker, Phys. Chem. Chem. Phys., 2010, 12, 2227.
33 E. Wirnhier, M. Döblinger, D. Gunzelmann, J. Senker,
B. V. Lotsch and W. Schnick, Chem.–Eur. J., 2011, 17, 3213.
34 L. Seyfarth, J. Sehnert, N. El-Gamel, W. Milius, E. Kroke,
J. Breu and J. Senker, J. Mol. Struct., 2008, 889, 217.
35 R. K. Harris, Analyst, 2006, 131, 351.
36 Accelrys software inc. MS Modeling v5.0.0.0 Copyright 2009.
37 W. A. Dollase, J. Appl. Crystallogr., 1986, 19, 267.
38 H. M. Rietveld, J. Appl. Crystallogr., 1969, 2, 65.
39 H. Toraya and F. Marumo, Mineral. J., 1981, 10, 211.
40 H. Sun, J. Phys. Chem. B, 1998, 102, 7338.
41 L. W. Finger, D. E. Cox and A. P. Jephcoat, J. Appl.
Crystallogr., 1994, 27, 892.
42 E. Salager, R. S. Stein, S. Steuernagel, A. Lesage, B. Elena
and L. Emsley, Chem. Phys. Lett., 2009, 469, 336.
43 M. H. Levitt, Encycl. Nucl. Magn. Reson., 2002, 9, 165.
44 D. Sakellariou, A. Lesage, P. Hodgkinson and L. Emsley,
Chem. Phys. Lett., 2000, 319, 253.
45 X. Zhao, W. Hoffbauer, J. S. auf der Günne and M. H. Levitt,
Solid State Nucl. Magn. Reson., 2004, 26, 57.
15 F. Richter and H.-W. Schmidt, Macromol. Mater. Eng., 2013,
298, 190.
46 J. P. Perdew and Y. Wang, Phys. Rev. B: Condens. Matter
Mater. Phys., 1992, 45, 13244.
16 H. Nakajima, M. Takahashi and Y. Kimura, Macromol.
Mater. Eng., 2010, 295, 460.
47 J. Senker, L. Seyfarth and J. Voll, Solid State Sci., 2004,
6, 1039.
17 H. Bai, W. Zhang, H. Deng, Q. Zhang and Q. Fu,
Macromolecules, 2011, 44, 1233.
18 P. Song, Z. Wei, J. Liang, G. Chen and W. Zhang, Polym. Eng.
Sci., 2012, 52, 1058.
19 M. Schmidt, J. J. Wittmann, R. Kress, D. Schneider,
S. Steuernagel, H.-W. Schmidt and J. Senker, Cryst. Growth
Des., 2012, 12, 2543.
20 M. Schmidt, J. J. Wittmann, R. Kress, H. W. Schmidt and
J. Senker, Chem. Commun., 2013, 49, 267.
48 F. W. Karau, L. Seyfarth, O. Oeckler, J. Senker, K. Landskron
and W. Schnick, Chem.–Eur. J., 2007, 13, 6841.
49 D. Hirsemann, T. K.-J. Köster, J. Wack, L. van Wüllen,
J. Breu and J. Senker, Chem. Mater., 2011, 23, 3152.
50 L. Seyfarth and J. Senker, Phys. Chem. Chem. Phys., 2009,
11, 3522.
51 F. Taulelle, Solid State Sci., 2004, 6, 1053.
52 J. Senker, J. Sehnert and S. Correll, J. Am. Chem. Soc., 2005,
127, 337.
21 R. Q. Albuquerque, A. Timme, R. Kress, J. Senker and
H.-W. Schmidt, Chem.–Eur. J., 2013, 19, 1647.
53 J. Sehnert and J. Senker, Chem.–Eur. J., 2007, 13, 6339.
54 J. Sehnert, K. Bärwinkel and J. Senker, J. Mol. Struct.
(THEOCHEM), 2007, 824, 58.
55 J. Sehnert, K. Baerwinkel and J. Senker, J. Phys. Chem. B,
2007, 111, 10671.
22 T. Govindaraju and M. B. Avinash, Nanoscale, 2012, 4, 6102.
23 M. Stöter, D. A. Kunz, M. Schmidt, D. Hirsemann, H. Kalo,
B. Putz, J. Senker and J. Breu, Langmuir, 2013, 29, 1280.
24 M. B. Avinash, K. S. Subrahmanyam, Y. Sundarayya and
T. Govindaraju, Nanoscale, 2010, 2, 1762.
56 J. Schmidt, A. Hoffmann, H. W. Spiess and D. Sebastiani,
J. Phys. Chem. B, 2006, 110, 23204.
25 K. S. Novoselov, D. Jiang, F. Schedin, T. J. Booth,
V. V. Khotkevich, S. V. Morozov and A. K. Geim, Proc. Natl.
Acad. Sci. U. S. A., 2005, 102, 10451.
26 J. C. Meyer, A. K. Geim, M. I. Katsnelson, K. S. Novoselov,
T. J. Booth and S. Roth, Nature, 2007, 446, 60.
27 A. K. Geim and K. S. Novoselov, Nat. Mater., 2007, 6, 183.
28 C. N. R. Rao, A. K. Sood, K. S. Subrahmanyam and
A. Govindaraj, Angew. Chem., Int. Ed., 2009, 48, 7752.
29 K. S. Subrahmanyam, P. Kumar, U. Maitra, A. Govindaraj,
K. P. S. S. Hembram, U. V. Waghmare and C. N. R. Rao,
Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 2674.
57 R. Harris and A. Olivieri, Prog. Nucl. Magn. Reson. Spectrosc.,
1992, 24, 435.
58 K. Eichele, WSolids1, version 1.20.17, Universität Tübingen, 2012.
59 Predicted NMR data calculated using Advanced Chemistry
Development, Inc. (ACD/Labs) Software V12.5 (© 1994–2013
ACD/Labs).
60 J. H. van Esch, F. Schoonbeek, M. de Loos, H. Kooijman,
A. L. Spek, R. M. Kellogg and B. L. Feringa, Chem.–Eur. J.,
1999, 5, 937.
61 M. de Loos, J. van Esch, R. M. Kellogg and B. L. Feringa,
Angew. Chem., Int. Ed., 2001, 40, 613.
30 J.-U. Kim, R. Davis and R. Zentel, J. Colloid Interface Sci.,
2011, 359, 428.
62 H.-Z. Guo, G.-D. Yin, N.-F. She and A.-X. Wu, Acta Cryst.,
2005, E61, 04062.
31 R. Davis, R. Berger and R. Zentel, Adv. Mater., 2007,
19, 3878.
63 J. Senker and J. Lüdecke, Z. Naturforsch., B: J. Chem. Sci.,
2001, 56b, 1089.
8796
|
CrystEngComm, 2013, 15, 8784–8796
This journal is © The Royal Society of Chemistry 2013