Crystal Growth & Design
Article
Synthesis of 2,4,6-trimethylpyridine N-oxide was adapted from the
synthesis of 2,6-dimethylpyridine 1-oxide in the literature.63 2,4,6-
Collidine (5 mL, 43 mmol), acetic acid (ca. 25 mL), and hydrogen
peroxide (ca. 20 mL) were mixed together and refluxed at 90 °C.
After 4 h, additional hydrogen peroxide (ca. 25 mL) was added, and
the reaction was left to reflux for 5 days. The reaction was monitored
by TLC analysis in 95:5 dichloromethane/methanol. Upon
completion, the reaction mixture was reduced to about a third of
its volume under reduced pressure and was diluted with an excess of
distilled ice water. The pH was then adjusted to ∼10 by use of K2CO3
and confirmed with litmus paper. The crude product was obtained via
extraction with CH2Cl2. The product was purified through column
chromatography by eluting with 1:1 hexane/ethyl acetate, then with
water content in the NMR solvent can compete with selenium
and form HB with PNO; (2) steric hindrance from PNO
allows the selenium to have only one ChB instead of acting as
bifurcated ChB donor.
Compound 2 and its ChB cocrystals were dissolved in
DMSO-d6 due to the reduced solubility of all tellurium-
containing samples in CDCl3. However, there is no consistent
increase or decrease in the chemical shifts of the cocrystals
observed compared to the value of pure telluradiazole 2 (δ =
2430.02 ppm). This inconsistency is attributed to the solvent
effect, where the oxygen atom in DMSO can also act as a ChB
acceptor and compete with the oxygen atom in the pyridine N-
oxides.
1
9:1 dichloromethane/methanol. H and 13C solution NMR experi-
ments were used to confirm the purity of the product. 13C NMR (300
MHz, CDCl3) δ in ppm: 148.47 (1C), 136.36 (1C), 125.06 (2C),
20.50 (2C), 18.50 (2C). 1H NMR (300 MHz, CDCl3) δ in ppm: 6.93
(s, 2H), 2.48 (s, 6H), 2.25 (s, 3H)
CONCLUSIONS
■
Nine new chalcogen-bonded cocrystals involving dicyanosele-
nodiazole/dicyanotelluradiazole and pyridine N-oxide deriva-
tives have been synthesized and characterized through a
combination of X-ray diffraction and NMR spectroscopy. The
geometric information demonstrates that these ChB are
moderately short and directional. Without steric hindrance,
cocrystals formed between dicyanoselenodiazole and pyridine
N-oxides featured a supramolecular tetrameric ChB synthon,
and cocrystals formed between dicyanotelluradiazole and
pyridine N-oxide derivatives exhibit an open spiral config-
uration. Different substituents at the para- position of pyridine
N-oxide result in a ChB distance trend similar to that in
previous studies of halogen-bonded systems: methoxy-
substituted PNO < phenyl-substituted PNO < methyl-
substituted PNO < PNO. However, these ChB distances do
not necessarily directly reflect the strength of ChB due to
additional hydrogen bonding stabilization of some complexes.
Both 77Se and 125Te CP/MAS SSNMR experiments reveal a
general increase in the δ22 and δ33 principal components of
chemical shift tensors for the chalcogen-bonded cocrystals in
comparison to the pure dicyano-1,2,5-seleno/telluradiazoles,
resulting in an increase in isotropic chemical shift and a
decrease in span values. Fine structure in the 77Se solid-state
NMR spectra originating from residual dipolar coupling and J
coupling to 14N was successfully modeled in order to
determine intramolecular J(14N, 77Se) coupling values.
Unfortunately, the changes observed upon cocrystallization
did not significantly exceed the errors on the data and
therefore no definitive trend resulting from chalcogen-
bonding-induced cocrystallization could be confirmed.
Cocrystallization. Equimolar amounts of ChB donor 1 or 2 and
ChB acceptors, 4-methylpyridine N-oxide (a), 4-methoxypyridine N-
oxide (b), 4-phenylpyridine N-oxide (c), 3,5-dimethylpyridine N-
oxide (d), 2,6-dimethylpyridine N-oxide (e), and 2,4,6-trimethylpyr-
idine N-oxide (f), were dissolved into a minimum volume of
chloroform for cocrystals involving selenium systems, or acetonitrile
or acetone for cocrystals involving tellurium systems. Slow
evaporation of these solvents at room temperature produced
cocrystals suitable for single-crystal X-ray diffraction. Solids were
stored in a refrigerator at ∼4 °C. Melting points were determined with
a MEL-TEMP electro-thermal instrument.
Cosublimation. 3,4-Dicyano-1,2,5-selenodiazole (1) and 2,6-
dimethylpyridine N-oxide (e) were added separately to opposite
ends of a 2.5 mm diameter glass tube. The tube was then sealed in
vacuo. In a home-built, two-zone tube furnace,51 the temperature of
each end of the tube was monitored separately, where the zone
containing starting material 1 was heated from 20 to 90 °C at a rate of
10 °C/h and the zone containing 2,6-dimethylpyridine N-oxide was
heated from 20 to 55 °C at a rate of 5 °C/h. Each end of the
sublimation tube was held at final temperatures for 10 h and was
allowed to slowly return to room temperature over 7 h. The
polymorph 1·e(II) was collected near the center of the tube.
Solution NMR Spectroscopy. 77Se and 125Te NMR spectra were
recorded using a 300 MHz Bruker Avance II NMR spectrometer at
ambient temperature. The external reference for 77Se was selenous
acid (1 M solution in D2O), with a chemical shift of 1300.1 ppm. The
external reference for 125Te was diphenyl ditelluride (0.5 M solution
in CDCl3) with the chemical shift set to 420 ppm. 0.01 M solutions
were prepared in CDCl3 and DMSO-d6 to acquire 77Se and 125Te
NMR spectra, respectively. Commercial deuterated solvents from
Cambridge Isotope Laboratories Inc. were used without further
purification.
Solid-State NMR Spectroscopy. Data were acquired with a 9.4
T magnet (νL(77Se) = 76.31 MHz and νL(125Te) = 126.24 MHz),
Bruker AVANCE III console, and a triple-resonance 4 mm MAS
probe (University of Ottawa, Ottawa, Canada). Samples were ground
into fine powders and packed into 4 mm o.d. zirconia rotors. 77Se
Overall, this work demonstrates that different chemical
substitution patterns on chalcogen bond acceptors can give rise
to different structural geometries and crystal packing arrange-
ments in the chalcogen-bonded cocrystalline products. These
systems are characterized by different NMR responses, thereby
contributing to a growing understanding of the impact of σ-
hole interactions on NMR interaction tensors.
chemical shifts were referenced to solid ammonium selenate (δiso
=
1040.2 ppm), and 125Te chemical shifts were referenced to solid
telluric acid (δiso = 685.5 and 692.2 ppm). A standard 1H→77Se/125Te
cross-polarization (CP) pulse sequence was employed for all the
cocrystals. The π/2 pulse length was 4.1 μs for 77Se and 3.4 μs for
125Te. The contact time was set to be 7 ms for 77Se and 2 ms for
125Te. The recycle delay ranged from 10 s to 4 min. The total number
of transients ranged from 1184 to 11 784. The read-out temperature
was held constant at 298 K for most of the experiments, or at 288 K
for compounds with a low melting point, using an FTS Systems TC-
84 temperature controller. To identify the isotropic peak and to
obtain spectra with a larger number of sidebands for spectral fitting
purposes, the SSNMR data were acquired with two different MAS
frequencies (3 kHz and 10 kHz for 77Se, 6 kHz and 11 kHz for 125Te).
EXPERIMENTAL SECTION
■
Synthesis. Starting materials were purchased from Sigma-Aldrich,
TCI, or Apollo Scientific. Commercial AR grade solvents were used
without further purification for the synthesis of 3,4-dicyano-1,2,5-
seleno/telluradiazoles and 2,4,6-trimethyl pyridine N-oxide, and for
the cocrystallization of chalcogen-bonded products. 3,4-Dicyano-
1,2,5-seleno/telluradiazoles were synthesized as previously reported.34
1H, 13C, and 77Se/125Te solution NMR experiments were used to
confirm the purity of the products.
H
Cryst. Growth Des. XXXX, XXX, XXX−XXX