α,α′,α′′-Tris(hydroxyimino)-1,3, 5-benzenetriacetonitrile: A three-fold symmetric, versatile and practical supramolecular building block

Article abstract of DOI:10.1039/c1ce05919j

The synthesis of a three-fold symmetric, aromatic molecule containing three co-planar effective hydrogen-bond moieties that can become a versatile and reliable hub for the assembly of extended, porous organic networks is presented.

Full text of DOI:10.1039/c1ce05919j

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a,a0,a00-Tris(hydroxyimino)-1,3,5-benzenetriacetonitrile: A three-fold
symmetric, versatile and practical supramolecular building block†
*
Christer B. Aakeroy, Michelle M. Smith and John Desper
€
Received 19th July 2011, Accepted 19th October 2011
DOI: 10.1039/c1ce05919j
acid moieties, (which frequently leads to unpredictable structures and
chemical compositions10). Against this background, we wanted to
design an alternative to trimesic acid as well as to other recently
reported trigonal molecules such as benzene-1,3,5-tri-p-phenyl-
phosphonic acid11 and 1,3,5-cyclohexanetricarboxylic acid.12
Our target, therefore, is an aromatic molecule with three-fold
symmetry containing three co-planar effective hydrogen-bond donor
moieties that, through less favorable self-complementarity and
improved solubility can become a versatile and reliable hub for the
assembly of extended, organic networks. A suitable molecule that
meets all requirements is a,a0,a00-tris(hydroxyimino)-1,3,5-benzene-
triacetonitrile, 2, Scheme 1, because aromatic cyanooximes are
capable hydrogen-bond donors,13 cyanooxime catemers and dimers
are less stable than carboxylic acid dimers,14 and solubilities of oximes
are generally superior to those of their acid analogues. Herein we
present the synthesis and characterization of 2 as well as the crystal
structure of a co-crystal of 2 and a symmetric ditopic hydrogen-bond
acceptor, 1,2-di(4-pyridyl)ethane, 3, Scheme 2, which displays
precisely the extended network structure that was desired and
postulated.
The synthesis of a three-fold symmetric, aromatic molecule con-
taining three co-planar effective hydrogen-bond moieties that can
become a versatile and reliable hub for the assembly of extended,
porous organic networks is presented.
Trimesic acid has achieved near-classic status as a building block in
structural chemistry1 and organic crystal engineering.2 Examples
include hexagonal sheets of trimesic acid with space-filling coronene
within the channels,3 the hydrogen-bond based complementarity of
1,3,5-tris(4-pyridyl)triazine with trimesic acid leading to a planar
architecture clathrated with pyrene,4 and starting with the crystal
structure determination of trimesic acid itself over forty years ago.5
This molecule has also been frequently employed in inorganic crystal
engineering, and recent interest in metal–organic frameworks6 clearly
demonstrates that trimesic acid remains an important and versatile
tecton for supramolecular synthesis. The general appeal of trimesic
acid7 is undoubtedly a result of its high symmetry that can be
promoted into extended networks through three directional
hydrogen-bonding (or metal-coordinating) sites. The co-planarity of
the binding sites allows for the production of flat layers with large
hexagonal channels, catenated and non-catenated structures,8 and
‘extended’ hexagonal networks through the use of symmetric ditopic
hydrogen-bond acceptors. However, given the potential structure-
building qualities, chemical simplicity, and commercial availability of
trimesic acid, there is arguably a disproportionately small number of
structure determinations of neutral organic architectures based
around trimesic acid.9 The reason for this can undoubtedly be traced
first to the poor solubility of trimesic acid. Generally speaking, as
most supramolecular synthesis is carried out in solution, it is
important that all reactants have comparable solubility if they are to
be assembled together into one crystalline heteromeric architecture
with desired connectivity and dimensionality. Second, since trimesic
acid displays perfect self-complementarity comprising particularly
strong intermolecular interactions, hydrogen-bond based acid/acid
dimers, it is difficult to make trimesic acid ‘abandon’ itself, without
having to resort to deprotonation of one or more of the carboxylic
Synthesis of 1: To a solution of 1,3,5-tris(bromomethyl)benzene
(3.02 g, 8.50 mmol) in THF (25 ml) was added sodium bicarbonate
(saturated solution, 30 mL) and sodium cyanide (4.17 g, 85.0 mmol),
followed by 30 mL water. The solution was left to stir for 48 h after
which it was acidified with 1 M HCl, and THF was removed via
rotary evaporation to leave behind an off-white solid. Yield: 1.53 g
(92%); 1H NMR (200 MHz, CDCl3): d 3.81 (s, 6H), 7.31 (s, 3H); IR: n
2253 cmꢀ1 (ChN); MP: 110–115 ꢁC. Despite repeated attempts we
were not successful at growing crystals of 1 suitable for single-crystal
X-ray diffraction.
Department of Chemistry, Kansas State University, Manhattan, KS,
66506, USA. E-mail: aakeroy@ksu.edu
† Electronic supplementary information (ESI) available: Experimental
data for synthesis and labeling scheme. CCDC reference number
708971. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1ce05919j
Scheme 1
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RESIdues, each containing one tris(oxime) and three half dipyridyl-
ethane molecules. Two of the three heterocycles exhibited criss-cross
disorder of the ethano linkage. Anisotropic thermal parameters for
closely spaced atoms on these fragments were pairwise constrained
using EADP commands. Relative occupancies of the species were
allowed to refine using free variables. Geometries of the molecules
were restrained using the SAME command.
Scheme 2
Significant residual electron density was present in the difference
Fourier map after taking into account the major species. For
purposes of refinement, several acetonitrile fragments were con-
structed using DFIX commands. Occupancy for each species was
refined during initial stages of data processing. Since the molecules
were close to inversion centers, suppression of bonds between unique
and equivalent molecules was achieved by using the PART –n
command. (With each molecule having occupancy of 50%, each
unique molecule can safely be assumed to be adjacent to a void.) No
attempt was made to locate or refine the solvent protons. Twelve of
the 20 strongest peaks in the final difference Fourier map, with
Synthesis of 2: Na metal (0.540 g, 23.5 mmol) was dissolved in
540 mL 2-propanol. 1 (0.80 g, 4.10 mmol) was dissolved in ꢂ100 mL
2-propanol and added to the sodium solution. Methyl nitrite gas was
generated in situ (see Supplementary details for full procedure) and
passed through the solution, which caused it to turn yellow. The
solution was left to stir for 5 days, after which a precipitate emerged.
This solid, the sodium salt of 2, was filtered off and dried. It was then
dissolved in water which was acidified to ꢂpH 2 whereupon a brown
precipitate appeared. In addition, 2-propanol was removed from the
first filtrate producing a small amount of solid which was re-dissolved
in water, acidified to ꢂpH 2, resulting in a brown precipitate. Both
solids were combined, dissolved in methylene chloride and a small
amount of methanol, and purified by column chromatography. (3 : 1
hexanes/ethyl acetate) to yield a colorless solid. Yield: 0.822 g (71%);
1H NMR (400 MHz, DMSO-d6): d 8.11 (s, 3H), 14.24 (s, 3H); 13C
NMR (400 MHz, DMSO-d6): d 110.34, 124.29, 130.49, 132.17; IR: n
2248 cmꢀ1 (ChN), n 1040 cmꢀ1 (N–O), n 3395 cmꢀ1 (O–H); MP:
240–245 ꢁC (decomp.). m/z: 305.06 (M + Na)+. We were not able to
grow crystals of 2 suitable for single-crystal X-ray diffraction.
Co-crystallization of a,a0,a00-tris(hydroxyimino)-1,3,5-benzene-
triacetonitrile 1,2-di(4-pyridyl)ethane, 2:3: 2 (5 mg, 0.0177 mmol) was
dissolved in ethyl acetate and added to a solution of 3 in ethyl acetate
(5.0 mg, 0.0266 mmol), and the resulting solution was left to evap-
orate at ambient conditions. This produced an off-white powder that
was recrystallized from acetonitrile to yield pale, yellow plates, mp:
246–248 ꢁC.
3
ꢀ
strongest peak at 0.94 electrons/A , are associated with solvent.
The crystal structure determination of 2:317 demonstrates that the
two components are present in a 1 : 1.5 ratio, which reflects the fact
that 2 has three hydrogen-bond donors and each dipyridyl molecule
contains two hydrogen-bond acceptors. The observed ratio means
that the numbers of donors and acceptors are matched perfectly and
each three-fold symmetric tecton forms three O–H/N hydrogen
bonds to three different dipyridyl units, Table 1, Fig.1.
As each dipyridyl moiety acts as a bridge between two tricya-
nooximes, the end result is an infinite 2-D assembly constructed from
three unique O–H/N hydrogen bonds, Fig. 2.
Each crystallographically unique layer is constructed by three
O–H/N hydrogen bonds (shown in Table 1, underscore 1 and 2,
respectively).
There are no O–H/N hydrogen bonds between layers and the
layer-layer orientation, which is slightly off-set, is therefore controlled
by relatively weak dispersion forces and is non-specific. The overall
structure looks deceptively open, but the lattice also contains several
disordered solvent molecules. The solvent is lost from the crystal
upon standing, which produces a microcrystalline powder. The ease
with which lattice solvent is lost can probably be attributed to the fact
X-ray data were collected on a Bruker Kappa Apex II four-circle
CCD diffractometer at 120 K using a fine-focus molybdenum Ka
tube. Data were collected using APEX215 software. Initial cell
constants were found by small widely separated ‘‘matrix’’ runs. An
entire hemisphere of reciprocal space was collected. Scan speed and
scan width were chosen based on scattering power and peak rocking
curves.
Table 1 Hydrogen-bond geometries in the crystal structure of 2:3a
Initial analysis of the dataset showed that the sample suffered from
merohedral twinning. Conversion of the triclinic unit cell using the
matrix [ꢀ1 0 0][1 ꢀ2 0][0 0 1] gave a cell that was nearly monoclinic
(C-centered) by metric (a ¼ 89.68ꢁ; g ¼ 90.32ꢁ) and symmetry
(Rmerg ¼ 23.9%) criteria. The existing triclinic HKLF 4 data were
converted to an HKLF 5 format, with twin law corresponding to 2-
fold rotation down the pseudo-monoclinic unique axis, using locally
written software. The ratio of the two twin components could then be
refined using the BASF command (which refined to ꢂ13%). Data
were reduced with SHELXTL.16 The structure was solved by direct
methods (on the original HKLF 4 format dataset) without incident.
All hydrogen atoms were assigned to idealized positions and were
allowed to ride. Heavy atoms were refined with anisotropic
thermal parameters. Absorption correction was not performed
(m ¼ 0.089 mmꢀ1).
<(DHA)ꢁ
157.8
ꢀ
D–H/A
r(D/A) A
2.609(2)
2.676(2)
2.718(3)
2.598(2)
2.620(4)
2.591(4)
O21_1–H21_1/
N31_1
O23_1–H23_1/
N41_1
O25_1–H25_1/
N51_1
O21_2–H21_2/
N31_2
O23_2–H23_2/
N41_2
O25_2–H25_2/
N51_2
170.6
161.6
157.7
157.5
165.8
a
OXX_1 and OXX_2 represent the unique oxygen atoms of the three
oximes on the two crystallographically unique tritopic oximes. NXX_1
and NXX_2 represent the hydrogen-bond acceptor sites located on
nitrogen atoms located on six unique bipyridine fragments (see ESI for
detailed labeling scheme).
The asymmetric unit contains two tris(cyanooximes), three dipyr-
idylethane molecules, and several solvent molecules. Excepting the
solvent molecules, the unit cell contents were divided into two
72 | CrystEngComm, 2012, 14, 71–74
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Fig. 1 The central motif in the crystal structure of 2:3; each molcule of 2
forms three O–H/N hydrogen bonds with neighboring pyridyl-based
molecules (disordered atoms removed for clarity).
Fig. 3 A view down the a- axis shows the channels (occupied by solvent
molecules, running through the crystal structure of 2:3.
all co-crystals containing a carboxylic acid-py, O–H/N, hydrogen
ꢀ
bond have O/N distances in the range of 2.54–2.73 A which further
illustrates that the cyano-oxime moiety is capable of forming
hydrogen-bonds of comparable strength as those displayed by
carboxylic acids.
The desired improvement in solubility vis-a-vis the analogous
carboxylic acid was attained; 2 is soluble in a variety of organic
solvents cf. ethanol, diethylether, ethylacetate and dichloromethane.
The synthesis and characterization of 2 as well as the demonstration
that this molecule can indeed produce porous crystalline molecular
solids indicate that 2 may offer a platform for several research
ventures in a variety of areas. For example, previous work has shown
that the assembly of porous monolayers/networks of trimesic acid on
gold19 and graphite20 surfaces is driven by intermolecular hydrogen
bonds, and it is likely that, in addition to the obvious opportunities
for cyanooxime-driven organic- and inorganic21 crystal engineering, 2
may also be a useful candidate for nanopatterning and deposition on
surfaces as it shares several important chemical/structural character-
istics with trimesic acid.22
Fig. 2 The extended hydrogen-bonded network in the crystal structure
of 2:3; disordered solvent molecules (removed for clarity) occupy the
space within the host structure.
We gratefully acknowledge financial support from NSF (CHE-
0957607) and from the Terry C. Johnson Center for Basic Cancer
Research.
that the relative orientation of neighbouring 2-D networks leads to
a 3-D architecture with continuous channels, Fig. 3. It is worth
noting, however, that the intended primary host network by itself is
not disrupted by any solute–solvent hydrogen-bonds
Notes and references
The hydrogen bonds between pyridyl and cyano-oxime moieties in
ꢀ
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€
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ꢁ
ꢀ
group P1, a ¼ 11.310(2); b ¼ 17.162(3); c ¼ 17.335(3) A, a ¼ 88.010
ꢁ
3
ꢀ
(10), b ¼ 82.742(3), g ¼ 70.891(10) , V ¼ 3153.8(11) A Z ¼ 2, Dc ¼
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ꢀ3
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74 | CrystEngComm, 2012, 14, 71–74
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