The Structure of Cis-2,2′-Azopyridine in the Solid State

Article abstract of DOI:10.1007/s10870-018-0737-z

Descriptions of azoheteroaromatic compounds in their cis-isomeric form in the solid state are almost non-existent. Cis-2,2′-azopyridine is a known compound which structure differentiates from the trans-isomer based on spectroscopic evidence (UV–Vis absorption, ¹H, and ¹³C NMR spectroscopy) and with studies regarding its stability, thermal reversion to the trans-isomer, and dipole moment in solution. However, the structure of this compound in the solid state has been unresolved. Herein, we present the crystal structure of cis-2,2′-azopyridine that forms red prismatic crystals in the monoclinic space group C2/c. The unit cell parameters are: a = 23.485 (4), b = 5.9241 (12), c = 21.656 (4) ?, and V = 2717.1 (9) ?³ with 12 molecules per unit cell. Molecules are arranged as two helical conformers (P and M) with C–N=N–C torsion angles and aromatic ring planes’ angles comparable to those reported for cis-azobenzene. Graphical Abstract: The rare structural determination of an azoheteroaromatic cis-isomer of 2-azopyridine that was synthesized, isolated and crystallized is presented. X-ray structure analysis reveals that the molecule forms dimeric complexes containing both M- and P-helical conformers as well as infinite stacked columns in the solid state through a combination of C–H?N hydrogen bonds, C–H?π interactions and lone pair?π contacts. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10870-018-0737-z

Journal of Chemical Crystallography
https://doi.org/10.1007/s10870-018-0737-z
BRIEF COMMUNICATION
The Structure of Cis-2,2′-Azopyridine in the Solid State
Iamnica J. Linares Mendez1,2 · Jeffrey S. Pleizier1 · Hong‑Bo Wang1,2 · James A. Wisner1,2
Received: 25 July 2018 / Accepted: 14 September 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Descriptions of azoheteroaromatic compounds in their cis-isomeric form in the solid state are almost non-existent. Cis-2,2′-
azopyridine is a known compound which structure differentiates from the trans-isomer based on spectroscopic evidence
(UV–Vis absorption, 1H, and 13C NMR spectroscopy) and with studies regarding its stability, thermal reversion to the trans-
isomer, and dipole moment in solution. However, the structure of this compound in the solid state has been unresolved.
Herein, we present the crystal structure of cis-2,2′-azopyridine that forms red prismatic crystals in the monoclinic space
group C2/c. The unit cell parameters are: a=23.485 (4), b=5.9241 (12), c=21.656 (4) Å, and V=2717.1 (9) Å3 with 12
molecules per unit cell. Molecules are arranged as two helical conformers (P and M) with C–N=N–C torsion angles and
aromatic ring planes’ angles comparable to those reported for cis-azobenzene.
Graphical Abstract
The rare structural determination of an azoheteroaromatic cis-isomer of 2-azopyridine that was synthesized, isolated and
crystallized is presented. X-ray structure analysis reveals that the molecule forms dimeric complexes containing both M-
and P-helical conformers as well as infinite stacked columns in the solid state through a combination of C–H⋯N hydrogen
bonds, C–H⋯π interactions and lone pair⋯π contacts.
Keywords Cis-isomer · Azoheteroaromatic · Diazene · Helical conformer
Introduction
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10870-018-0737-z) contains
supplementary material, which is available to authorized users.
Aromatic azo compounds have been in the interest of chem-
ists since the beginning of the second half of the nineteenth
century [1]. Initially, this interest was centered in their use
as dyes and pigments in the textile and food industry. It was
* James A. Wisner
jwisner@uwo.ca
Extended author information available on the last page of the article
Vol.:(0123456789)
1 3

Journal of Chemical Crystallography
after Hartley’s report over the influence of light in the con-
figuration of the N=N double bond [2] when their applica-
tions extended to the field of molecular switches [3–6].
Generally, the trans-isomeric form is the most stable
one, and the cis form is subject to thermal reversion to the
trans-isomer. The main reference is azobenzene, the trans-
isomer of which is approximately 12 kcal mol−1 more stable
than the cis-isomer [7], with an activation energy for the
cis→trans thermal transition of 23 kcal mol−1 in solution
and 31 kcal mol−1 in the solid state [7, 8]. According to
the Cambridge Structural Database (CSD) there are 1509
azo aromatic containing crystal structures of which approxi-
mately 77 occurred as cis-isomers at the time of this sub-
mission. Most of these crystal structures corresponded to
ortho-substituted azobenzenes and/or azo aromatic moieties
comprised in a macrocycle. In the first case, the stability of
the cis-isomer is attributed to the repulsion of ortho-substit-
uents with a N lone pair [9] of the azo function, σ-electron-
withdrawing effect when fluorine atoms are employed [10],
or to the steric hindrance provided by bulky alkyl groups
[11]. In the second case, the stability of the cis-isomer in
a macrocycle is rationalized in terms of the reduction in
ring strain when at least one azo group is in such configura-
tion [12, 13], or to a high entropic contribution in the acti-
vation energy during the thermal reversion [14, 15]. The
isolation of the cis form of fluorine-substituted azobenzene
compounds in a crystal lattice has being exploited by Bar-
ret and Friščić to promote photomechanical non-reversible
isomerization [16–18].
lack of crystallographic information regarding cis-azo-
heteroaromatic systems reported in the literature. To our
knowledge, the only report of this type corresponds to that
of cis-1,2-di[(4,4′-bipyridine)-3-yl]diazene by He and cow-
orkers in 2016 [23]. Here we report the crystal structure of
cis-2,2′-azopyridine.
Experimental Section
The starting material (2-aminopyridine) was used as
obtained from Oakwood Chemical; oxidant (sodium
hypochlorite) was used as commercially available dissolved
in water (5% w/v; i.e. bleach). The solvents used (diethyl
ether and acetone) were procured by CALEDON Labora-
tory Chemicals. Column chromatography was performed
with SiliCycle®SiliaFlash® F60, 40–63 µm 60 Å. 1H NMR
(400 MHz) and 13C (100 MHz) spectra were recorded on a
Mercury 400 MHz spectrometer. 1H and 13C spectra were
referenced relative to tetramethylsilane (TMS) using the
residual non-deuterated NMR solvent signal. Mass spectra
were recorded using electron impact ionization on a Finni-
gan MAT 8200 spectrometer.
Synthesis of Trans‑2,2′‑Azopyridine
Trans-2,2′-azopyridine was synthesized beginning from
2-aminopyridine as reported by Brown and Granneman
[19] (Scheme 1). A solution of 2-aminopyridine (5.00 g,
53.1 mmol) in water was cooled to 0 °C in an ice-salt
bath. A cold aqueous NaClO solution (237 mL of 5% w/v,
159 mmol) was added dropwise to the 2-aminopyridine solu-
tion over a period of 30 min. During the addition, the tem-
perature was maintained below 5 °C. The reaction mixture
was then left to stir for a further 5 h allowing it to reach
room temperature. Extraction with diethyl ether was per-
formed (3 × 50 mL), the isolated organic phase was dried
with MgSO4 and filtered. The solvent was removed under
reduced pressure, and the product recrystallized from hex-
Compared to azobenzene, azoheteroaromatic systems
have been less frequently examined, even though some of
these molecules share important properties with azoben-
zene derivatives. For example, symmetrical azopyridines
(2,2′-azopyridine, 3,3′-azopyridine and 4,4′-azopyridine)
have cis–trans activation energies on the order of the
azobenzene analogue (i.e., 21.0, 22.6 and 21.4 kcal mol−1
in solution, respectively) [19]. The potential for hydrogen
bonding to nitrogen lone pairs in these examples [20] gives
rise to the prospective study of azoheteroaromatic deriva-
tives as hydrogen bond arrays. In this regard, the use of
heteroaromatic moieties (such as pyridyl, pyrimidyl, tria-
zine and naphthyridyl) and a nitrogen atom from the azo
group have been explored as hydrogen bond acceptor
arrays in molecular recognition [21, 22]. In light of these
similarities and potential applications, there is a remarkable
1
anes to yield deep red crystals. Yield = 0.83 g (17%). H
NMR (400 MHz, CDCl3) = δ (ppm) 8.79 (d, 2H, J=4.7 Hz),
8.01 (d, 2H, J=8.2 Hz), 7.94 (dd, 2H, J=8.2, 1.6 Hz), 7.48
(dd, 2H, J=4.7, 1.2 Hz). 13C NMR (150 MHz, CDCl3): δ
(ppm) 162.7, 149.6, 138.5, 126.1, 115.4. HRMS (EI): Calc.
for C12H8N4 =186.0749; found 186.0899.
Scheme 1 Synthesis of trans-
and cis-2,2′-azopyridine. a
NaClO (3 eq.), water, 0 C, 5 h.
b 350 nm, acetone, 5 h
1 3

Journal of Chemical Crystallography
Table 1 Crystal data and structure refinement for cis-2,2′-azopyridine
Isolation of Cis‑2,2′‑Azopyridine
CCDC reference
1574612
C10H8N4
184.20
Monoclinic
C2/c
23.485 (4)
5.9241 (12)
21.656 (4)
90
115.608 (7)
90
2717.1 (9)
12
1152
110
1.54178
1.351
0.705
13,701
2302
Trans-2,2′-azopyridine (500 mg, 2.72 mmol) was dissolved
in 200 mL of acetone and split into several test tubes capped
with a septum and sealed with parafilm. These samples were
irradiated for 5 h in a Luzchem photoreactor (model LZC-
4V) equipped with 14 UVA bulbs centered at 350 nm. After
irradiation, samples were combined in a flask wrapped in alu-
minium foil to exclude light, and the acetone was removed
by application of a stream of dry air until a red oil remained.
The oil was subjected to flash chromatography in the dark
using diethyl ether as eluent. The first eluting fraction was
collected, and the ether was removed by a constant flow of dry
air to yield cis-2,2′-azopyridine as a red solid. Yield=225 mg
(45%). The product was stored in a freezer protected from
Chemical formula
Molecular weight (g mol−1
)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (º)
β (º)
γ (º)
V (Å3)
Z
F (000)
T (K)
1
light until required. H NMR (400 MHz, CDCl3) = δ
(ppm) 8.12–8.14 (m, 2H), 7.74–7.79 (m, 2H), 7.39 (d, 2H,
J=7.7 Hz), 7.04–7.07 (m, 2H). 13C NMR (150 MHz, CDCl3):
δ (ppm) 164.5, 147.8, 137.8, 122.4, 118.6. HRMS (EI): Calc.
for C12H8N4 =186.0749; found 186.0752.
λ (Å)
Dcalc (g cm−3
)
∝ (Cu-Kα) (mm−1
)
Total reflections
Independent reflections
Absorption correction
Refinement on
X‑Ray Crystallography
Multi-scan
F2
A suitable single crystal (0.29 × 0.26 × 0.22 mm3) was
mounted on a Mitgen polyimide micromount with a small
amount of Paratone N oil. X-ray diffraction data were col-
lected on a Bruker-Nonius Kappa CCD Apex2 X-ray dif-
fractometer using graphite monochromatic Cu-Kα radiation
(λ = 1.54178 Å) at 110 K. The frame integration was per-
formed using SAINT [24]. The resulting data was scaled,
and absorption corrected using a multi-scan averaging of
symmetry-equivalent data using SADABS [25]. The struc-
ture was solved by using a dual space methodology using
the SHELXT program [26]. All non-hydrogen atoms were
obtained from the initial solution. The hydrogen atoms
were introduced at idealized positions and were allowed to
refine isotropically. The structural model was fit to the data
using full matrix least-squares based on F2. The structure
was refined using the SHELXT program from the SHELX
suite of crystallographic software [27]. Figures were cre-
ated with the Diamond software package [28]. Details for
the data collection and the structure refinements are given
in Table 1, and the crystallographic information file (CIF)
deposited with the Cambridge Crystallographic Data Centre
(http://www.ccdc.cam.ac.uk; deposition number 1574612)
and provided as Electronic Supplementary Material.
Parameters refined
R(F0) [l>2σ(l)]
Rw(F0 ) [l>2σ(l)]
238
0.0352
0.0886
0.0448
0.0932
1.069
2
R(F0) (all data)
2
Rw(F0 )(all data)
GOF on F2
protected from light. The red prisms obtained are mono-
clinic and belong to the C2/c space group. The asymmet-
ric unit comprises 1.5 molecules; wherein one molecule
sits fully on a general position (molecule A), and the
other molecule sits on a two-fold rotation axis (molecule
B). Besides their position within the unit cell, cis-2,2′-
azopyridine molecules can be differentiated by their heli-
cal conformation. From the 12 molecules within each unit
cell, half exhibit P helicity (right-handed helix) and the
other half M helicity (left-handed helix; Fig. 1a) [29–31].
In both conformations, the nitrogen atoms are arranged in
an endogenous manner (i.e. syn–syn) which is in accord-
ance with the dipole moment in benzene reported by Vogel
and co-workers [32]. The angles between the pyridyl ring
least squares planes are 57.6° and 64.1° for molecules A
and B, respectively; which are similar to that observed in
cis-azobenzene (64.3°) [33, 34]. The C–N=N–C torsion
angles for molecules A and B were 9.8° and 9.1°, respec-
tively. The pyridyl ring dispositions are in agreement with
the chemical shift of the aromatic protons when compared
with the trans-isomer. The 1H and 13C NMR spectra of the
Discussion
Single crystals of cis-2,2′-azopyridine (suitable for X-ray
diffraction) were obtained by slow diffusion of diisopropyl
ether into a concentrated diethyl ether solution at 298 K
1 3

Journal of Chemical Crystallography
Fig. 1 a Stick representation of
the X-ray crystal structure of
molecule A dimer: P helicity
conformer (top left), M helicity
conformer (bottom right). C–
H⋯N contacts and C–H⋯π
interactions indicated (dashed
orange lines). Blue, grey, and
white colors correspond to
nitrogen, carbon and oxygen
atoms, respectively. b Crystal
lattice of cis-2,2′-azopyridine
along the b-axis. Green and blue
structures correspond to mol-
ecules A and B, respectively.
(Color figure online)
cis-isomer display upfield shifts due to the magnetic ani-
sotropic effect of the aryl rings. The average bond length
between the nitrogen atoms in the azo group is 1.25 Å; the
average bond length between the nitrogen atom of the azo
group and its attached carbon is 1.44 Å (Table 2). Com-
pared to trans-2,2′-azopyridine, these cis-isomeric bond
lengths are slightly longer by approximately 0.01 Å [35].
Overall, the structural parameters of cis-2,2′-azopyridine
are very similar to those reported by Mostad and Rømming
for cis-azobenzene [34].
columns of molecule B as a result of the glide plane in the
c axis direction.
Along the b-axis, molecules are arranged in a columnar
fashion with a periodicity of 5.92 Å. A C–H⋯π interac-
tion is observed between all molecules A related by two-
fold screw translation along the b axis (C7A–H7A⋯least
squares pyridyl plane=3.12 Å; Fig. 2). On the other hand,
molecules B are stacked upon each other with close con-
tacts between the azo nitrogen atoms and ortho-pyridyl
carbon atoms of the corresponding symmetry-related mol-
ecule (N1B⋯C5B=3.24 Å; Fig. 3). These contacts can be
understood as the manifestation of a lone pair-π interaction
between adjacent molecules as observed previously in many
reports [36, 37].
Regarding the arrangement of cis-2,2′-azopyridine
molecules within the crystal lattice, molecules A and
B are displayed in alternating columns along the a-axis
(Fig. 1b). Molecules A are arranged as dimers containing
an inversion center; therefore, each dimer comprises a P
and M helicity conformer (Fig. 1a). A closer look at the
dimer shows the presence of two intermolecular interac-
tions involving the ortho pyridyl proton H1A: a C–H⋯N
contact (C1A–H1A⋯N1A′ = 3.40 Å, C1A–H1A⋯N1A′ =
2.53 Å, ∠C1A–H1A⋯N1A′ = 151.8°); and a C–H⋯π inter-
action (C1A–H1A⋯pyridyl least squares plane’ = 3.06 Å,
C1A–H1A⋯pyridyl centroid’ = 3.38 Å; ‘indicates interac-
tion with symmetry related atom/group). Conversely, each
column of B molecules has only one conformer (P or M).
There is an alternation between P and M isomers across
Supplementary Material
CCDC entry 1574612 contains the supplementary crystal-
lographic data for cis-2,2′-azopyridine from this report.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via http://www.ccdc.
cam.ac.uk/data_request/cif; or, by e-mailing data_request@
ccdc.cam.ac.uk.
Table 2 Selected bond
Molecule A
Molecule B
1.4417 (19)
Trans-2,2′-azopyridine
lengths and angles of cis-2,2′-
azopyridine and trans-2,2′-
azopyridine [35] in the solid
state
C–N(azo) bond length (Å)
N=N bond length (Å)
1.4434 (21)
1.4421 (17)
1.2479 (16)
64.070 (49)
1.4316 (16)
1.2524 (23)
57.605 (44)
1.2455 (14)
0.000 (52)
Angle between least square pyridyl
planes (°)
C–N=N–C torsion angle (°)
9.809 (217)
9.085 (212)
180.000(92)
1 3

Journal of Chemical Crystallography
Fig. 2 Stick representation
of the X-ray crystal structure
of molecules A related by
b-axis translation with C–H⋯π
interactions indicated (dashed
orange lines). Blue, grey, and
white correspond to nitrogen,
carbon, hydrogen and oxygen
atoms, respectively. (Color
figure online)
Fig. 3 Stick representation of
the X-ray crystal structure of
molecules B related by b-axis
translation with N⋯C contacts
indicated (dashed orange lines).
Blue, grey, and white cor-
respond to nitrogen, carbon,
hydrogen and oxygen atoms,
respectively. (Color figure
online)
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68:8291–8304
Acknowledgements We wish to thank the Natural Science and Engi-
neering Research Council of Canada, the National Natural Science
Foundation of China (No. 21302232), Wuhan Science and Technology
Bureau (No. 2015011701011599), Program for Excellent Young Inno-
vative Research Team in the Higher Education Institutions of Hubei
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Affiliations
Iamnica J. Linares Mendez1,2 · Jeffrey S. Pleizier1 · Hong‑Bo Wang1,2 · James A. Wisner1,2
2
Iamnica J. Linares Mendez
ilinare@uwo.ca
Key Laboratory of Optoelectronic Chemical Materials
and Devices, Ministry of Education, School of Chemical
and Environmental Engineering, Jianghan University,
Wuhan, Hubei, China
Jeffrey S. Pleizier
jpleizie@uwo.ca
1
Department of Chemistry, Western University, 1151
Richmond Street, London, ON N6A 5B7, Canada
1 3