Self-Assembly of n-Alkyl- and Aryl-Side Chain Ureas and Their Derivatives as Evidenced by SEM and X-ray Analysis

Article abstract of DOI:10.1002/ejoc.201501242

A small library of ureas and related compounds was synthesized and examined by scanning electron microscopy (SEM), single-crystal X-ray diffraction, powder X-ray (pXRD), and polarized optical microscopy (POM) techniques in order to elucidate the factors controlling their self-assembly in the solid state. Inspection of the 12 solid-state structures revealed that molecules in the crystal lattice are held together by intermolecular H-bonding, π-π stacking as well as C-H/π interactions. The same interactions are likely responsible for the formation of supramolecular aggregates (e.g. sheet-like assemblies, micro- and nano-fibers, and the porous networks easily identifiable by SEM technique) and in certain cases led to the small molecules gelation.

Full text of DOI:10.1002/ejoc.201501242

FULL PAPER
DOI: 10.1002/ejoc.201501242
Self-Assembly of n-Alkyl- and Aryl-Side Chain Ureas and Their Derivatives as
Evidenced by SEM and X-ray Analysis
Oleg V. Kulikov,*[a] Dumindika A. Siriwardane,[a] Gregory T. McCandless,[a]
Charles Barnes,[b] Yulia V. Sevryugina,[c] Joseph D. DeSousa,[a] Jingbo Wu,[a]
Roger Sommer,[d] and Bruce M. Novak*[a]
Keywords: Supramolecular chemistry / Self-assembly / Gelation / Nanofibers / Ureas
A small library of ureas and related compounds was synthe- intermolecular H-bonding, π–π stacking as well as C-H/π in-
sized and examined by scanning electron microscopy (SEM),
single-crystal X-ray diffraction, powder X-ray (pXRD), and
polarized optical microscopy (POM) techniques in order to
teractions. The same interactions are likely responsible for
the formation of supramolecular aggregates (e.g. sheet-like
assemblies, micro- and nano-fibers, and the porous networks
elucidate the factors controlling their self-assembly in the so- easily identifiable by SEM technique) and in certain cases
lid state. Inspection of the 12 solid-state structures revealed
that molecules in the crystal lattice are held together by
led to the small molecules gelation.
elastomers mechanical properties tuning.[21] Another
emerging area of ureas applications is a design of supra-
molecular LMWGs (low-molecular-weight gelators),[23]
“unimolecular” co-catalysts for cooperative ring-opening
polymerization,[24a] and developing the synthetic foldamers
capable to adopt a single screw sense.[24b–24d] In order to
clarify how changes in structure influence the self-assembly
properties in the solid state, we prepared and inspected by
SEM, powder XRD, polarized optical microscopy (POM),
and single-crystal X-ray diffraction analysis a small library
of ureas as well as some of their derivatives bearing alkyl
substituents varying in length and having different aromatic
moieties. We report here the synthesis and morphological
characterization of 25 mono-, bis-, tris-ureas as well as bis-
carbodiimide and diazetidine (Chart S1). We assume that
our structural findings (especially, with regard to the nano-
fibers) can be used for the potential industrial applications
such as design of the materials possessing high non-linear
optical anisotropy properties,[25] creation of degradable
polymers for regenerative medicine,[26] wound debride-
ment,[27] as promising degradable elastomeric materials for
the tissue engineering,[28] and the development of scaffolds
loaded with antibacterial drugs and enzymes.[29]
Introduction
Simple ureas as well as complex molecules incorporating
ureido groups have attracted considerable attention as
transmembrane ion transporters,[1–8] anion receptors,[9–12]
and transdermal penetration enhancers for drug deliv-
ery.[13,14] Besides their well-known ability to form strong
intermolecular N–H···O=C hydrogen bonds[15,16] allowing
more efficiently to deliver drugs by amphiphilic block co-
polymers,[17a] ureas are of considerable interest for supra-
molecular polymer chemistry.[17b] Recent developments are
concerned of hydrogen-bonded urea based supramolecular
polymers,[18] which easily undergo intensive intermolecular
self-organization process caused by directional H-bonding
interactions. Introduction of the urea groups capable of
making strong H-bonds in polymer backbone might repre-
sent significant interest for multiple potential applications
of such nanoribbon/fiberlike morphological systems.[19–22]
Moreover, bis-urea molecules are known to serve as
“supramolecular reinforcement fillers” for thermoplastic
[a] Department of Chemistry, University of Texas at Dallas,
Richardson, TX, 75080, USA
E-mail: oleg.kulikov.chem@gmail.com
Bruce.Novak@utdallas.edu
Results and Discussion
http://www.utdallas.edu/chemistry/faculty/novak.html
[b] Department of Chemistry, University of Missouri-Columbia,
Columbia, MO, 65211, USA
Synthesis
[c] Department of Chemistry, Texas Christian University,
Fort Worth, TX, 76129, USA
Synthesis of the ureas of interest was performed by stan-
dard techniques (mostly, by condensation of the corre-
sponding amine and isocyanate, ESI vol. 1) in moderate to
high yield (Scheme 1).
[d] Department of Chemistry, North Carolina State University,
Raleigh, NC, 27695, USA
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201501242.
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Scheme 1. Structures of ureas and their derivatives used in this study.
X-ray Studies (Single Crystal and Powder pXRD)
ure S24; 2.03, 2.04 Å for 12, Figure S31) or N–H···S=C
contacts (2.68 Å for 1, Figure S1; 2.58 Å for 11, Figure S26)
Single crystal X-ray studies of target molecules (Fig- forming 6- and eight-membered patterns. Notably, thiourea
ures 1, 2, Supporting Information: S1–S38; Table S1) such 11 represents different polymorph of already known
as N-methyl-NЈ-[2-methyl-6-(1-methylethyl)phenyl]thiourea APAJOR[30] structure developed by Steed lab. It appears
(1); N-(benzo-15-crown-5)-NЈ-methylthiourea (2); N-(1,3- that the difference in molecular structure for thiourea 11
benzodioxol-5-ylmethyl)-NЈ-phenylurea (3); N,NЈ-bis(1,3- and APAJOR is the conformation around terminal C–N
benzodioxol-5-ylmethyl)urea (4); (S,S)-N,NЈ-bis(1-phenyl- bonds. This resulted in dramatic changes in both molecular
ethyl)urea (5); (R,R)-N,NЈ-bis(1-cyclohexylethyl)urea (6a); structure and crystal lattice packing (Figure 1, S27, S28).
1,3-bis(4-methoxybenzyl)urea
(7);
N-[(2-nitrophenyl)-
We assume that urea molecules form supramolecular ag-
methyl]-NЈ-(1-naphthyl)urea (8); N,NЈ-1,2-ethanediyl-bis- gregates through intermolecular H-bonding as well as π–π
NЈЈ-methylurea (11); N,NЈ-1,2-ethanediyl-bis-NЈЈ-hexylurea stacking and C–H/π interactions.[31] The presence of mul-
(12); 4,4Ј-bis(3-phenylcarbodiimide)diphenylmethane (15); tiple distinct peaks in the powder X-ray diffraction patterns
1,3-diphenyl-2,4-diphenylimino-1,3-diazetidine, (17) re- of ureas and their derivatives (Table S2, Figure S40–S50)
vealed that molecules adopt non-planar conformation and confirmed high crystallinity of these compounds. The max-
in the crystal lattice interact through intermolecular H- ima observed probably relate to the interchain distances
bonding (N–H···S=C 2.49, 2.51 Å for 2, Figure 1, S2; N– and layer separation in the crystal lattice.
H···O=C 2.08, 2.22 Å for 3, Figure S3; 2.03 Å for 4, Figure
In particular, reflection peaks at 2θ ≈ 20–30° (d ≈ 4–3 Å)
S6; 2.08 Å for 5, Figure S9; 2.13 Å for 6a, Figure S15; 2.01, can potentially be attributed to the π–π stacking interaction
2.05, 2.09, 2.21 Å for 7, Figure S19; 2.01, 2.18 Å for 8, Fig- of the adjacent aromatic fragments. This is in accordance
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Self-Assembly of n-Alkyl- and Aryl-Side Chain Ureas
Figure 1. Left side: single-crystal X-ray data (partial crystal packing diagram) for (benzo-15-crown-5)-Me-S-urea (2) highlighting intermo-
lecular H-bonding as well as plausible π–π stacking interactions between aromatic rings of the adjacent molecules (non-polar hydrogen
atoms are omitted for clarity, space-filling representation is given below); right side: comparison of Me-bis-S-urea (11) with its APAJOR
(CCDC-795072) conformational isomer.
as well as a “zig-zag” (with intermolecular dihedral angles
of the ureido group alternating between approximately
+47.7° and –47.7°). Figure 2, S24 display this alternating
structural arrangement. Plausible intermolecular π–π inter-
actions between nitrophenyl and naphthyl groups with
centroid-to-centroid distance of 3.78, 3.95 Å and dihedral
angle of ca. 5.2° have been identified. This interaction is
confined to “pairs” since the next neighboring molecule will
have a dihedral angle equal in magnitude, but opposite in
direction (a part of the “zig-zag” packing pattern), and,
therefore, a longer separation distances (4.48, 6.07 Å). The
intramolecular dihedral angle between the nitrophenyl and
naphthyl groups is ca. 68.6°. Our rationale for the use of
urea 8 was that introducing naphthyl moiety would possibly
increase π–π stacking if compared with the other aromatic
ureas in this study (e.g. ureas 1–5, 7) not having fused aro-
matic rings. Similarly, the presence of four aromatic frag-
Figure 2. Selected centroid (Ar)···centroid (Ar) distances for NO2-
ments in the structure of carbodiimide 15 would likely en-
hance π–π interactions between the adjacent molecules re-
sulting in formation of the supramolecular stack (Figure 3,
left panel). The same kind of “π–π enforcement” could be
achieved by appending three hydrogen-bonding thiourea
moieties to triazine core in urea 16a structure (Figure 3,
right panel). Presumably, individual tris-urea 16a molecules
in hypothetical stack are held together by combination of
hydrogen bonds between thiourea groups as well as π–π in-
teractions of seven aromatic rings.
Bzl-Naphth-urea (8) (non-polar hydrogen atoms are omitted for
clarity).
with single-crystal X-ray data showing plausible π–π and
C–H/π stacking (Figure 1, S2, S4, S20, S22–S24, S33).
However, in certain cases (Figure S1, S3, S6, S9, S19, S36),
intermolecular distances between aromatic rings are signifi-
cantly longer than the currently accepted maximum dis-
tance for π–π interactions. Thus, urea 8 exhibited the dis-
tance between the ring centroids 3.78, 3.95 Å and 4.48,
We should also note that Ph-CHMe-urea (5) (Figure S9)
6.07 Å, correspondingly (Figure 2). Notably, along with the has been previously reported (EFETEQ, CCDC-978481).
hydrogen bonding interactions of the ureido group (e.g. The known structure (CCDC-978481) and urea 5 are nearly
–NH–CO–NH–), between neighboring molecules of 8, the identical. In both cases the molecule sits on a twofold axis
packing conformation along the crystallographic “a” direc- through the C=O bond. As expected, the anomalous dis-
tion can be described as “head-to-tail” (with nitrophenyl persion refinement of the Flack parameter determined for
group as the “head” and the naphthyl group as the “tail”) urea 5 points to the correct absolute configuration.[32]
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Figure 3. Single crystal X-ray data (partial crystal packing diagram) for Ph-bis-carbodiimide 15 (left) and hypothetical stack of TRZN-
Ph-tris-S-urea (16a) (right).
Morphology Studies by SEM and Gelation Behavior
We hypothesize that intermolecular hydrogen bonding as
well as the other types of non-covalent weak interactions
revealed by X-ray studies are responsible for organizing
urea molecules into supramolecular aggregates that could
be visualized by SEM and POM techniques. Inspection of
ureas by SEM showed great variety of morphologies such
as fibers, plate-like aggregates, porous networks, rod-like
assemblies, etc. (Figures 4, 5, 6, and 7, Supporting Infor-
mation: 2S1–2S108; Table 2S1).
Figure 5. SEM images of NO2-Bzl-Naphth-urea (8) deposited from
1,4-dioxane, 33 mg/mL (panel a); urea 8 deposited from THF,
22 mg/mL (panels b, c); (1,3-dioxolane-Bzl)-Ph-urea (3) as a solid
obtained by crystallization from EtOH (panel d); urea 3 deposited
from THF, 66 mg/mL (panels e, f); Ph-bis-S-urea (14) obtained by
precipitation from EtOAc/MeOH (panel g); C12-Ph-urea (10b) de-
posited from THF, 66 mg/mL (panel h); C12-Br-Ph-urea (10a) as a
solid obtained by crystallization from EtOAc/EtOH (panel i).
Figure 4. SEM images of C6-bis-Me-urea (13) as a solid obtained
by crystallization from DMF (panel a); C18-Br-Ph-urea (9c) de-
posited from THF, 66 mg/mL (panels b–d); C18-NO2-Bzl-urea (9b)
tures. As a result of losing THF molecules during solvent
deposited from THF, 66 mg/mL (panels e, f).
evaporation, large cavities could be generated that is clearly
Micrographs of bis-urea 13 (Figure 4, a, Supporting In- seen in the panels of Figure 4, c and f, Supporting Infor-
formation: 2S65–2S71) displayed clearly identifiable fi- mation: 2S41, 2S46. Changing the solvent system dramati-
brillar network patterns that were presumably formed due cally effects molecules self-organization. Thus, 9c (when
to the bundling of individual urea fibers when prepared the crystallized from the mixture EtOH/CHCl3) produced ran-
specimen by crystallization from different solvents includ- domly oriented fibers that fuse and split forming network
ing EtOH (2S65, 2S66), DMF (2S67–2S71). Patterns ob- (Figure 2S42, 2S43). Detailed morphological features of the
served are typical in appearance for most of the images col- self-assembled aggregates based on long-chain tris-ureas
lected for ureas in this study as well as for their derivatives. (e.g. dodecyl and octadecyl) have been recently communi-
Inspection of the ureas 9c and 9b deposited from the high cated.[33a,33b] Reversible tris-urea gelators incorporating
concentration stock solutions (THF, 66 mg/mL) revealed phenylureido groups similar to 16a structure have been syn-
interesting porous self-assembled morphologies (Figure 4, thesized and inspected by SEM.[33c] Randomly oriented fi-
b–f, Supporting Information: 2S39–2S41, 2S44–2S48). It bers are apparent in the panels a–c of the Figure 5 dis-
seems likely that, due to the conformational freedom of the playing self-assembled morphologies derived from urea 8
flexible octadecyl substituents in both ureas, hydrophobic with estimated bent fiber width Ն300 nm (1,4-dioxane, Fig-
pockets could be formed where solvent molecules are en- ure 2S27b) and Ն200 nm (THF, Figure 2S31c).
trapped and, therefore, decreasing the crystallinity of mate-
Use of EtOH as a solvent for urea 8 crystallization al-
rial comparative to their short chain homologous struc- lowed to acquire images of shorter rod-like aggregates (Fig-
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Self-Assembly of n-Alkyl- and Aryl-Side Chain Ureas
Figure 6. SEM images of the dried gels of C6-bis-urea (12) (panels a, b) and C18-NO2-Bzl-urea (9b) (panels c, d) deposited from PhNO2,
66 mg/mL.
aggregates became the predominant motif (Figure 2S9–11).
Lower row panels g–i of the Figure 5 demonstrate aggre-
gated planar sheets and very distinct fibrous structures ob-
tained from urea 14 as well as long-chain ureas 10a and 10b
bearing dodecyl substituent. Additional SEM micrographs
displaying fibrillary morphologies/plate-like aggregates for
compounds 10a, 10b and 14 could be found in Figure 2S50–
2S60, 2S72–2S76. Importantly, well-defined plates orga-
nized into 3D-network and having thickness ranging from
348 nm to 477 nm could be observed in the panels of Fig-
ure 2S76 (urea 14), whereas 10b demonstrated pretty dense
plate packing arrangement (280–661 nm in thickness for the
individual plates, Figure 2S58). Notably, deposition of urea
10b from THF stock (66 mg/mL) resulted in formation of
quite unusual rose-like aggregates (Figure 5, h, Fig-
ure 2S60). These observations are in accordance with the
previous results from Hamilton lab[34] detailing the synthe-
sis and self-assembly properties of polymerizable organogel-
ators and the low molecular weight gelators incorporating
ureido moieties. Also, the recent contributions to urea-
based supramolecular gels[23,35] area should not be under-
estimated.
Figure 7. SEM images of the dried gels of C18-NO2-Bzl-urea (9b)
(panels a–f) deposited from CHCl3, 20 mg/mL and 4-F-Ph-bis-urea
(14c) deposited from the hot DMF stock solution, 80 mg/mL
(panels g–i).
ures 2S32–2S34) thus implying that solvent choice has an
Despite the fact that gelation is not the focus of current
effect on self-assembly in the solid state. More morpho- work, we decided to inspect aggregation behaviour of se-
logies of this nature have been deposited in ESI, vol. 2 (Fig- lected ureas in order to evaluate their propensity to form
ures 2S24–2S34). Figure 5 (d–f) showed uniform bundled fi- gels using the same solvent, concentration, and SEM sam-
brous aggregates of urea 3 depending on solvent – (EtOH, ple preparation method (Figure 2S93–2S108, Table 2S2).
panel d) and THF (panels e, f). Drop cast deposition from Compounds 8, 9a–9c, 10a, 10b, 12, and 13 have been found
THF stock solution (66 mg/mL) displays clearly identifiable to form organogels when their respective stock solutions in
nanofibers (ca. 600 nm in width, Figure 2S4–2S8) that at the nitrobenzene (66 mg/mL) were cooled down to the
high magnification (5, 10 kϫ) appear to be the clusters of room temperature (Figure 2S93). Importantly, urea 10b
ribbon-like aggregates (Figure 2S8a–c). Again, changing the having relatively short dodecyl aliphatic chain produced
solvent (e.g. THF to EtOH) and the sample preparation leaking gel, while model urea 11 with terminal methyl
caused noticeable changes in appearance – short rod-like groups found to be soluble in the nitrobenzene with no gel-
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O. V. Kulikov, B. M. Novak et al.
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ling at the ambient temperature. Other seven ureas tested be considered as over-simplification in terms of their ability
clearly demonstrated formation of the slightly turbid stable to form extensive hydrogen bonding and π-stacking motifs
gels upon cooling. This is not unexpected since longer alkyl comparatively to their bis- and tris-urea analogues, most of
chains (C18- vs. C12- and methyl in case of urea 11) as well them exhibited very distinctively looking morphologies
as the presence of two ureido groups in one molecule in when examined by SEM.
case of compounds 12 and 13 should facilitate the gel for-
In addition to that, we have studies morphologies as-
mation. Evidently, naphthyl group in compounds 8 and 9a sembled from fluorinated bis-ureas (14a–14c, Figure 7, g–i,
might assist effective gelation too due to the increased abil- 3S1–3S22, Table 3S1) in order to elucidate the role of strong
ity to form supramolecular π–π stacks. Nitrobenzene was electron-withdrawing substituents in aggregation behaviour.
selected for a gel testing because of its high boiling point Interestingly, compound 4-F-Ph-bis-urea (14c) tends to
and, as a consequence, low volatility, although ureas gela- form rose-like aggregates when deposited from the hot
tion was detected in some other solvents such as CHCl3 and DMF stock solution on the glass slide (cold deposition of
DMSO as well (Figure 2S85–2S92). Also, all ureas tested the same bis-urea yielded less ordered sheet-like aggregates,
showed good solubility in the nitrobenzene at high concen- Figure 3S17). Somewhat similar was observed for 4-CF3-
tration when heated, unlike the other solvents. The latter Ph-bis-urea (14b), e.g. plate-like aggregates are clearly vis-
appears to be highly important to prepare SEM specimens ible in the panels of Figures 3S9 and 3S10. We assume that
under the same experimental conditions for comparison along with classical intermolecular N-H···O=C hydrogen
purpose. SEM inspection of the dried gels exhibited simi- bonding, weak Caryl-H···F interactions of the adjacent mol-
larly looking fibrous motifs (Figure 6, 2S94–2S108).
ecules or even C–F···C=O orthogonal interactions[36a]
Figure 6 demonstrated aggregates obtained from ureas might be involved in determining the orientation of fluorin-
9b and 12 when dissolved in the nitrobenzene and cooled ated urea molecules with respect to each other and, conse-
down to the room temperature. Panels a and b showed no quently, resulting in formation of these unusual supra-
meaningful differences compared to the previously de- molecular assemblies, however this is not clear enough to
scribed fiber-like structures, whereas panels c and d both be convincing. All fluorinated ureas were found to form gels
depicted not well resolved intertwining bundles of fibers as in either DMF or PhNO2 at 80 mg/mL, moreover C6F5-bis-
the major morphological feature of compound 9b. This may urea (14a) bearing perfluorinated pendant groups seemed
be indicative of low crystallinity of 9b that was also evi- to be the strongest gelator capable of producing stiff trans-
denced by the corresponding pXRD profile (Figure S50). parent supramolecular gel (Figure 3S6–3S8, 3S18, 3S19) in
Interestingly, the presence of octadecyl alkyl chain pro- both solvents.
motes the formation of spherical sponge-like aggregates
(Figure 7, a–f, 2S86–2S89). Again, the latter phenomenon
the best could be explained by liberating CHCl3 molecules
Polarized Optical Microscopy (POM) Studies
from hydrophobic pockets formed by long aliphatic chains
during specimen preparation.
The polarized optical microscopy images have been re-
corded for certain ureas (Figures 8, 9, 2S109–2S123) show-
In general, analysing the library of SEM images collected ing magnificent birefringent textures and rod-like aggre-
for mono-, bis- and tris-ureas as well as their derivatives gates indicative of formation the highly ordered, crystalline
(bis-carbodiimide 15 and the product of diphenylcarbo- domains as a result of self-assembly.
diimide dimerization – diazetidine 17), we infer that de-
Figure 8 displayed crystalline arrangements obtained
pending on structure and solvent used for the sample prepa- from the ureas 1 and 5 in THF. Interestingly, mono-urea 1
ration, molecules of the tested compounds tend to form di- failed to provide visible images under polarized light at typ-
verse morphologies with predominance of rod-like and ical concentration range used (22–66 mg/mL), probably as
fiber-like aggregates. Although the use of mono-ureas may a result of very high solubility in this particular solvent
Figure 8. POM micrographs (10ϫ) of (2-isopropyl-Ph)-Me-S-urea (1) deposited from THF, 560 mg/mL (a); Ph-CHMe-urea (5) deposited
from THF, 33 mg/mL (b).
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Self-Assembly of n-Alkyl- and Aryl-Side Chain Ureas
Figure 9. POM micrographs (10ϫ) of NO2-Bzl-Naphth-urea (8) deposited from 1,4-dioxane, 33 mg/mL (panel a) and from PhNO2,
66 mg/mL, gel (panel b).
(THF). Nevertheless, high concentration stock solution stacking propensity allowing to control aggregation in
(560 mg/mL) could be used to generate the images of rod ureas. Another important finding was the morphological
shaped structures (Figure 8, a, 2S120), thus providing un- changes have occurred upon changing the solvent, concen-
ambiguous evidence for urea liquid crystalline proper- tration, and deposition temperature that might be employed
ties.[34a,36b,36c] Similarly, bis-urea 11 formed aggregates (Fig- to grow specific motifs (e.g. needle-like aggregates, bent
ure 2S122) when deposited from PhNO2 stock solution fibers, ribbons, rose-like plates, etc.). These urea-based
(66 mg/mL) in the form of crystals that are markedly morphologies might be applicable for designing the novel
smaller than motifs depicted on the panel a of Figure 8. functional materials.
Also, urea 10b colourful textures (Figure 2S123) found to
be collapsible into crystalline network upon specimen aging
(ca. 1 month) as shown in Figure 2S124. Figure 9 showed
Experimental Section
General Methods: All starting materials used were obtained from
Sigma–Aldrich, Fluka or TCI America and were used without fur-
ther purification unless otherwise noted. Thin-layer chromatog-
raphy (TLC) was performed on Sigma–Aldrich TLC Plates (silica
gel on aluminum, 200 mm layer thickness, 2–25 mm particle size,
60 Å pore size). 1H nuclear magnetic resonance spectra were re-
corded either on Bruker Avance IIITM 500 instrument at 500 MHz
or Mercury 400BB at 400 MHz. 13C NMR spectra were recorded
on the same instruments at 125 MHz and 100 MHz, correspond-
POM images of urea 8 acquired in 1,4-dioxane (panel a)
and nitrobenzene (panel b). These observations are consis-
tent with rectangular/hexagonal columnar liquid crystal
superstructures discovered for mono-urea molecules bear-
ing C8-, C12-, and C16-substituents.[36b]
Conclusions
1
ingly. H and 13C chemical shifts are reported in parts per million
In summary, a small family of simple ureas as well as
compounds derived from them, has been synthesized and (ppm) relative to the corresponding residual solvent peak. High-
resolution electrospray mass spectra (HR-ESI MS) were obtained
on Agilent technologies 6530 Accurate Mass QT of LC/MS instru-
ment at University of Texas at Austin, Chemistry Department
Mass Spectrometry Facility. Powder X-ray diffraction (pXRD) data
profiles were recorded on Rigaku Ultima III XRD diffractometer
(Nano Characterization Facility at UTD).
inspected by combination of single-crystal X-ray diffraction
analysis, powder XRD, SEM, and POM techniques. Urea
molecules proved to self-assemble in the solid state into
various aggregates and this process is likely driven by
hydrogen bonding, π–π, and C-H/π-stacking interactions of
the adjacent molecules aromatic moieties as evidenced by
X-ray diffraction analysis. For the ureas bearing either alkyl
side chains or fluorinated substituents, the other factors
such as hydrophobic side chain/side chain interactions and/
or non-classical Caryl-H···F and C–F···C=O orthogonal
interactions should not be underestimated since they help
stabilize molecules in supramolecular network. This is espe-
cially pronounced in ureas bearing multiple fluorine atoms,
thus effecting self-association of individual molecules and,
consequently, gelation. At least seven out of eight non-
fluorinated ureas tested in the nitrobenzene (8, 9a–9c, 10a,
10b, 12, and 13) clearly exhibited gelating ability. The mor-
phologies observable by SEM and POM techniques are be-
lieved to be directly related to the aforementioned non-
covalent interactions leading to the formation of supra-
molecular aggregates. Also, introducing additional ureido
moieties/aromatic fragments would likely enhance π–π
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, spectroscopic data for all novel
ureas as well as single-crystal X-ray diffraction data can be found.
Acknowledgments
Funding of this work was provided by the Faculty start-up fund
from the University of Texas at Dallas (UTD) and the Endowed
Chair for Excellence at UTD. We wish to thank Mr. Kyle Johnson
for the preparation of urea 2. We gratefully acknowledge the
National Science Foundation (NSF) (NSF-MRI grantCHE-
1126177) used to purchase the Bruker Advance III 500 NMR in-
strument.
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Received: September 28, 2015
Published Online: October 28, 2015
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