Redetermination and Density Functional Studies of N,N′-(Disulfanediyldibenzene-2,1-Diyl) Dipyridine-2-Carboxamide

Article abstract of DOI:10.1134/S0022476618080061

The title compound C₂₄H₁₈N₄O₂S₂ is synthesized via the azide method and its structure is redetermined at 100(2) K. The title structure, N,N′-(disulfanediyldibenzene-2,1-diyl)dipyridine-2-carboxamide i

Full text of DOI:10.1134/S0022476618080061

Journal of Structural Chemistry. Vol. 59, No. 8, pp. 1797-1803, 2018.
Original Russian Text © 2018 S. Ö. Yıldırım, Z. Büyükmumcu, Ş. D. Doğan, R. J. Butcher.
REDETERMINATION AND DENSITY FUNCTIONAL
STUDIES OF N,N′-(DISULFANEDIYLDIBENZENE-2,1-DIYL)
DIPYRIDINE-2-CARBOXAMIDE
1
S. Ö. Yıldırım , Z. Büyükmumcu , Ş. D. Doğan ,
2
3
4
and R. J. Butcher
The title compound C24H18N4O2S2 is synthesized via the azide method and its structure is redetermined at
100(2) K. The title structure, N,N′-(disulfanediyldibenzene-2,1-diyl)dipyridine-2-carboxamide is
redetermined from the data published by Lumb, Hundal, and Hundal (Inorg. Chem., 2014, 53, 7770-7779).
The redetermination is of significantly higher precision than a previous low-temperature structure and the
improvement of the present redetermination consists in a released geometry of the 1,2-diphenyldisulfane
group. The molecular structure crystallizes in the triclinic space group, P-1, with a = 7.3492(3) Å,
b = 11.6753(5) Å,
c = 13.1814(6) Å,
α = 95.077(4)°,
β = 105.316(4)°,
γ = 100.759(4)°,
and
3
V = 1060.28(8) Å . The S–S bond length of 2.0758(4) Å and S–C distances of 1.7818(13) Å and
1.7767(13) Å for this redetermination are much closer to those observed in comparable structures. Intra-
and intermolecular N–H…S, N–H…N, C–H…O, C–H…S hydrogen bonds are present in the crystal
structure. The molecular geometry of the title compound is optimized by the DFT method and the
calculated geometrical parameters are compared with experimental ones. The NBO analysis of possible
intramolecular hydrogen bonds is made on the optimized structure for comparison.
DOI: 10.1134/S0022476618080061
Keywords: structural analysis, acyl azide, density functional theory, NBO analysis.
INTRODUCTION
Acyl azides, which are highly reactive, are very important compounds in organic chemistry. They give two main
reactions based on rearrangement and substitution. In the former, called the Curtius rearrangement, the acyl azide group
rearranges to the isocynate group upon exposure to mild external heat or irridation. The isocynate intermediate reacts with
amine to yield urea derivatives. In the latter, the substittution reaction of acyl azide with the amino group gives the
corresponding amides in the presence of bases [1].
Herein, we report a simple, fast and inexpensive synthetic methodology for the synthesis of N-(2-(2-(2-
picolinamido)-phenyl)disulfanyl)phenyl)picolinamide [2] (4) via the substitution reaction of the acyl azide form of 2-
picolinic acid (1).
1
Department of Physics, Faculty of Sciences, Erciyes University, Kayseri, Turkey; ozturk@erciyes.edu.tr.
3
2
Department of Chemistry, Faculty of Sciences, Erciyes University, Kayseri, Turkey. Department of Chemistry, Howard
4
University, Washington DC 20059, USA. Department of Pharmaceutical Basic Sciences, Faculty of Pharmacy, Erciyes
University, Kayseri 38039, Turkey. The text was submitted by the authors in English. Zhurnal Strukturnoi Khimii, Vol. 59,
No. 8, pp. 1861-1867, November-December, 2018. Original article submitted September 21, 2017.
0022-4766/18/5908-1797 © 2018 by Pleiades Publishing, Ltd.
1797

EXPERIMENTAL AND COMPUTATIONAL METHODS
Synthesis. To a solution of 2-picolinic acid (1) (0.5 g, 4.1 mmol) in 10 ml THF at –5 °C, triethylamine (0.57 ml,
4.1 mmol) in 5 ml THF was added dropwise and stirred. After 30 min, the cooled ethyl chloroformate solution (0.39 ml,
4.1 mmol) in 5 ml THF was added slowly and stirred at –5 °C for 30 min. In the last step, the solution of sodium azide
(0.52 g, 8.2 mmol) in 5 ml water was added dropwise and stirred at room temperature overnight. The resulting mixture was
extracted with ethyl acetate (3×15 ml) and the organic phase was washed with saturated sodium bicarbonate (3×30 ml) and
water (2×25 ml) and dried over MgSO4. After ethyl acetate was removed, 0.40 g of azide 2 was obtained. Without any
purification, the obtained acyl azide was used immediately [1]. Acyl azide 1 (0.40 g, 2.7 mmol) and 2-aminothiophenol (3)
(0.34 g, 2.7 mmol) in benzene (20 ml) was stirred at 70-80 °C for 24 h. The formed precipitate was filtered off and washed
with benzene. The resulting residue was purified by crystallization from EtOH and N-(2-(2-(2-picolinamido)-phenyl)disulfa-
nyl)phenyl)picolinamide (4) was obtained as a white solid. Isolated yield is 55%. Urea derivative 5 was not isolated. The ratio
1 1
of amine 4 to urea 5 (4:1) was determined using crude H NMR. H NMR (400 MHz, DMSO) δ 10.88 (s, 1H), 8.58 (d,
J = 4.4 Hz, 1H), 8.20 (d, J = 8.2 Hz, 1H), 8.15-8.00 (m, 2H), 7.74-7.64 (m, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.25 (t, J = 7.7 Hz,
13
1H), 6.99 (t, J = 7.5 Hz, 1H). C NMR (100 MHz, DMSO) δ 161.86, 149.23, 149.02, 139.38, 138.75, 136.15, 131.84, 127.61,
125.09, 124.99, 122.52, 120.72.
1
13
Instrumentation. H- and C-NMR spectra were recorded on a Bruker AM 400 spectrometer (at 400 MHz and
100 MHz, respectively) in a DMSO-d6 solution. Coupling constants J are reported in Hertz to the nearest 0-5 Hz. Deuterated
solvents were used for the homonuclear lock, and the signals were referenced to the deuterated solvents peaks.
X-ray crystallography. A single rectangular plate of the C24H18N4O2S2 compound, with the dimensions of
0.3×0.20×0.04 mm was used for data collection. The X-ray diffraction study was made on an Oxford Gemini-R single crystal
diffractometer. The system was prepared with plane graphite monochromatized MoK (λ = 0.71073 Å) radiation at 100(2) K.
α
The crystal orientation, cell refinement, and intensity measurements were performed using the CrysalisPro program. A multi
scan absorption correction was applied to the X-ray data collection. A total of 15616 reflections (8613 unique) within the θ
range (3.468 < θ < 35.318°) were collected in the ω scan mode. The integration method is used for absorption correction with
Tmin = 0.936 and Tmax = 0.990. The structures were solved by a direct method using the SHELXT program, and refined by
2
full-matrix least-square techniques against F using SHELXL2016/6 [3]. H atoms on N atoms were located in difference
maps and refined isotropically. The remaining H atoms were positioned geometrically and treated as riding, with
C–H = 0.95 Å and Uiso(H) = 1.2Ueq(C). ORTEP-3 [4] for the Windows program was used for generating the structure. The
final refinement with 297 parameters converged at R1 = 0.0476 and goodness of fit was 1.058. The largest and lowest electron
3 3
density peaks for were 0.475 e/Å and –0.320 e/Å , respectively.
Computing details. CrysAlis PRO 1.171.38.43 [5] analytical numeric absorption correction using a multifaceted
crystal model based on expressions derived by R. C. Clark and J. S. Reid [6]. Empirical absorption correction using spherical
harmonics, implemented in the SCALE3 ABSPACK scaling algorithm.
The molecular geometry of the title compound has been optimized using the nonempirical meta-GGA functional
TPSSTPSS [7] with the 6-31G(d,p) basis set. The vibrational spectrum of the optimized structure has been calculated to
check if the structure is at the minimum of the potential energy surface. The Mulliken charge distribution and frontier orbital
energy levels have been obtained using the optimized geometry. All of the calculations have been carried out with the
Gaussian 09 program package [8].
RESULTS AND DISCUSSION
Desired compound 4 was synthesized via the azide method used in this study. 2-Picolinic acid (1) was first
converted into corresponding azide 2. For the azidination reaction, 2-picolinic acid (1) was treated with ethyl chloroformate
in the presence of triethylamine followed by the addition of a solution of NaN3 in water to give azide 2 (Scheme 1). Acyl
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azide 2 was allowed to reflux in benzene for 24 h with 2-aminothiophenol (3). Contrary to expected, acyl azide gave
a substitution reaction and finally the amide was formed as a major compound and the urea derivative was formed as a minor
product in a ratio of 4:1. During the acyl azide substitution reaction, the disulfide bond formation can take place
1
13
spontaneously and quickly without any oxidant effect. The H and C NMR spectra enabled the assignment of the structures
of N-(2-(2-(2-picolinamido)-phenyl)disulfanyl)phenyl)picolinamide (4). The structure was further confirmed by single crystal
X-ray diffraction studies.
Scheme 1. Synthesis of N-(2-(2-(2-picolinamido)-phenyl)disulfanyl)phenyl)picolinamide (4) from 2-
picolinic acid (1).
X-Ray analysis of the title compound. The three-dimensional structure of N-(2-(2-(2-picolinamido)-
phenyl)disulfanyl)phenyl)picolinamide (4) was evaluated by X-ray crystallography as shown in Fig. 1. Selected bond lengths
and angles are listed in Table 1. Hordvik [9] gives a correlation between the S–S distance and the dihedral angle around it;
the present values of 2.23(15)° and 88.92(10)° agree with this. All bond lengths are in agreement with the values reported in
the literature [10, 11]. The torsion angles S2–S1–C1–C2 of –93.86(10)° and S2–S1–C1–C6 of 88.92(10)° are comparable in
2,2′-diaminodiphenyl disulfide (83.6° and 83.4°) [12], which indicates that there does not seem to be a pπ–dπ interaction
between the fully occupied p orbital on the C atom with an empty d orbital on the S atom in the latter compound. The N-
z
phenylbenzamide units are planar (maximum deviations 0.018(1) Å for C1 and 0.032(1) Å for C7). The structure consists of
Fig. 1. Molecular structure of the title compound with
atom labelling. Displacement ellipsoids are drawn at the
50% probability level.
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TABLE 1. Selected Molecular Structure Parameters of the Title Compound
Experimental
(XRD), Å
Calculated
(TPSS), Å
Experimental
(XRD), Å
Calculated
(TPSS), Å
Bond lengths
Bond lengths
S1–C1
S1–S2
1.7818(13)
2.0758(4)
1.78886
2.15233
1.78885
1.23775
1.23775
1.37825
1.39708
N2–C12
N2–C8
1.3359(17)
1.3430(16)
1.3585(15)
1.3943(16)
1.3389(18)
1.3418(16)
1.34318
1.34962
1.37825
1.39708
1.34318
1.34962
S2–C13
O1–C7
O2–C19
N1–C7
N1–C6
1.7767(13)
1.2193(15)
1.2238(15)
1.3593(16)
1.3952(16)
N3–C19
N3–C18
N4–C24
N4–C20
Experimental
(XRD), deg.
Calculated
Experimental
(XRD), deg.
Calculated
Bond angles
Bond angles
(TPSS), deg.
(TPSS), deg.
C1–S1–S2
C13–S2–S1
C7–N1–C6
C12–N2–C8
C19–N3–C18
C24–N4–C20
C6–C1–S1
104.33(4)
105.15(4)
128.86(11)
116.89(12)
129.47(11)
116.86(11)
120.22(9)
106.63706
106.63630
128.77193
117.55381
128.77193
117.55374
121.50119
C18–C13–S2
O1–C7–N1
120.12(10)
125.35(13)
125.78(12)
116.78(11)
118.18(11)
116.84(11)
121.50133
126.13736
126.13723
117.33071
118.88921
117.33092
O2–C19–N3
N2–C8–C7
N3–C18–C13
N4–C20–C19
Experimental
(XRD), deg.
Calculated
Experimental
(XRD), deg.
Calculated
Torsion angles
Torsion angles
(TPSS), deg.
(TPSS), deg.
S2–S1–C1–C2
S2–S1–C1–C6
S1–C1–C6–N1
C6–N1–C7–O1
N1–C7–C8–N2
–93.86(10)
88.92(10)
2.23(15)
–1.0(2)
–85.61591
98.59704
–3.53334
1.17364
S1–S2–C13–C14
S1–S2–C13–C18
S2–C13–C18–N3
O2–C19–C20–N4
–86.34(10)
97.21(10)
–85.62200
98.58961
–3.25(15)
–3.53120
–172.67(12)
–178.96052
4.38(16)
0.99335
two planar N-phenylbenzamide moieties related by an improper rotation of –89.1° about the S–S bond. The pyridine and
benzene rings have very different dihedral angles (24.39(1)° and 8.68(1)°) between them. The dihedral angles between the
benzene and pyridine rings are 25.09(1)° and 8.12(1)°. The conformation is stabilized by two bifurcated intramolecular
N–H…(S, N) hydrogen bonds. In the solid state, the structure is stabilized by C–H…O and C–H…S hydrogen bonds as
shown in the packing diagram along the b axis (Fig. 2, Table 2).
Theoretical analysis. The optimized geometry of the title compund is given in Fig. 3. As seen from the figure, the
optimized geometry is very similar to the structure obtained by XRD (Fig. 1). However, in contrast to the structure
determined by XRD in the solid state form, the geometry optimization by the DFT functional has been made in the gas phase
where there are no intermolecular interactions. Some selected geometrical parameters obtained by the experiment and theory
are given in Table 3. The structure has a dimeric character where two parts are connected to each other via S atoms. As
concluded from the S2–S1–C1–C2 and S2–S1–C1 –C6 dihedral angles which have values of –93.86 and 88.92, respectively,
two parts are approximatley parallel. As expected, the corresponding theoretical values (–85.61591 and 98.59704) have
a larger deviation from 90 deg due to the absence of the intermolecular interaction. Also, the S–S bond connecting the two
parts has a bond length value of 2.0758 Å which is less than the corresponding theoretical value of 2.15233 Å. The other
bond lengths obtained by the experiment and DFT are in agreement with each other in comparison to S–S bond lengths.
Mulliken charges accumulated on the atoms [13] are given in Fig. 3. The title compound includes the H, C, S, O,
and N atoms, having electronegativity values (in Pauling scale) of 2.2, 2.55, 2.58, 3.44. and 3.04, respectively. As expected
from the fact that two identical atoms with the same environment, two S atoms have 0 charges. Although O is the most
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Fig. 2. A view along the b axis of the crystal packing of
the title compound. The hydrogen bonds are shown as
dashed lines.
TABLE 2. Hydrogen-Bond Geometry (Å, deg.)
D–H⋯A
D–H
H⋯A
D⋯A
D–H⋯A
N1–H1N⋯S(1)
N1–H1N⋯N(2)
N3–H3N⋯S(2)
N3–H3N⋯N(4)
C5–H5A⋯O(1)
C12–H12A⋯S(2)
0.817(18)
0.817(18)
0.837(18)
0.837(18)
0.95
2.601(17)
2.172(18)
2.502(17)
2.172(18)
2.36
2.9967(12)
2.6372(16)
2.9805(10)
2.6325(16)
2.9276(17)
3.8773(14)
2.9126(17)
3.8822(15)
111.4(15)
116.2(15)
117.4(15)
114.5(14)
118.2
i
0.95
2.99
155.8
C17–H17A⋯O(2)
0.95
2.29
122.2
ii
C24–H24A⋯S(1)
0.95
2.93
177.7
i ii
Symmetry codes: –x+1, –y, –z+1; –x+2, –y+1, –z+1.
Fig. 3. Optimized geometry of the title compound with Mulliken
charges.
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TABLE 3. Donor NBO and Acceptor NBO Interactions for the Hydrogen Bonds
Donor NBO(i)
Acceptor NBO (j)
E(2), kcal/mol
E(j) – E(i), a.u.
F(i,j), a.u.
LP(1)S1
LP(2)S1
LP(1)S2
LP(2)S2
LP(1)O1
LP(2)O1
LP(1)O2
LP(2)O2
LP(1)N2
LP(1)N2
LP(1)N4
LP(1)N4
BD*(1)N1–H1N
BD*(1)N1–H1N
BD*(1)N3–H3N
BD*(1)N3–H3N
BD*(1)C5–H5A
BD*(1)C5–H5A
BD*(1)C17–H17A
BD*(1)C17–H17A
BD*(1)N1–H1N
BD*(1)C12–H12A
BD*(1)N3–H3N
BD*(1)C24–H24A
0.46
1.71
0.46
1.71
0.64
1.18
0.64
1.18
2.74
1.06
2.74
1.06
1.02
0.63
1.02
0.63
1.13
0.70
1.13
0.70
0.73
0.78
0.73
0.78
0.027
0.042
0.027
0.042
0.034
0.037
0.034
0.037
0.057
0.037
0.057
0.037
electronegative atom which has a charge value of –0.516, the N atoms connected to the two C atoms and one H atom have
a more negative value (–0.673). Because O atoms share bonding electrons only with one relatively electropositive atom, C
and N atoms share three bonding electrons with three relatively electropositive atoms (two C and one H atom). All the
hydrogen atoms have a positive charge since it is the atom with the lowest electronegativity. The C atom may have both
positive and negative charge values depending on the electronegativities of atoms it is bonded to.
HOMO and LUMO shapes of the molecule are given in Fig. 4. Electrons in HOMO spread out the molecule with the
exception of the pyridine cycle (there is a very small contribution from the N atom of the pyridine cycle). However, electrons
spread accross the entire molecule in the case of LUMO. The HOMO and LUMO energy levels have been calculated to be
–5.19 eV and –2.50 eV, respectively. According to the Koopman theorem [14], the reverse sign of HOMO and LUMO are
the first ionization energy and the first electron affinity of the molecule. Their values are 5.19 eV and 2.50 eV, respectively.
The possible hydrogen bonds are shown as dashed lines in Figs. 1 and 2. Since intermolecular interactions have not
been studied in the theoretical part of this work, only intramolecular hydrogen bonds can be investigated. In addition to
geometrical parameters, the NBO analysis [15] have been performed to get more insight on the possible hydrogen bonds. The
NBO second-order perturbation interaction energies of is a measure of the strength of a donor-acceptor interaction. For
hydrogen bonds, lone pairs of electronegative atoms act as donors while the antibond of X–H atom behaves as an acceptor,
where X is another electronegative atom. Since the structure is dimeric, it is expected that each interaction should be
observed twice, which is confirmed in Table 3. The hydrogen bonding interaction with the highest stabilization energy is the
interaction between the pyridine N atom and N–H on the bridge. The interaction with the second highest strength is the
interaction between the second lone pair of S and the antibonding orbital of N–H on the bridge. The weakest interaction takes
Fig. 4. HOMO and LUMO of the molecule.
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place between the first lone pair of S and the antibonding orbital of the N–H bond. According to the results of the NBO
analysis, there is no H-bonding interaction between two repeating parts of the molecule.
CONCLUSIONS
In this study, N,N′-(disulfanediyldibenzene-2,1-diyl)dipyridine-2-carboxamide has been synthesized via the acyl
1
13
azide method and characterized by spectroscopic ( H NMR and C NMR) methods and single crystal XRD. The comparison
between the calculated results and the X-ray experimental data indicate that theTPSS method shows good agreement with the
experimental results. The NBO analysis shows that there are 8 intramolecular hydrogen bonding interactions and the strength
of these interactions has been compared with the help of second-order perturbation energies obtained in this analysis.
The X-ray crystallographic data for the structures reported in this article have been deposited with CCDC as
supplementary data CCDC No. 1563555. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/ structure-
summary-form the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; E-mail:
deposit@ccdc.cam.ac.uk.
R. J. Butcher is grateful for funding from NSF (award 1205608) and the Partnership for Reduced Dimensional
Materials for partial funding of this research, to Howard University Nanoscience Facility for access to liquid nitrogen, and the
NSF–MRI program (grant No. CHE0619278) for funds to purchase the X-ray diffractometer and Research Foundation of
Erciyes University (Project Number: TCD-2015-5602) for their financial support of this work.
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