Crystal structures and density functional theory calculations of o - And p-nitroaniline derivatives: Combined effect of hydrogen bonding and aromatic interactions on dimerization energy

Article abstract of DOI:10.1021/cg4005714

The interplay of strong and weak hydrogen bonds, dipole-dipole interactions, and aromatic interactions of o- and p-nitroaniline derivatives was studied by combining crystal structure analysis and density functional theory (DFT) calculations. Crystal struc

Full text of DOI:10.1021/cg4005714

Article
pubs.acs.org/crystal
Crystal Structures and Density Functional Theory Calculations of o-
and p‑Nitroaniline Derivatives: Combined Effect of Hydrogen
Bonding and Aromatic Interactions on Dimerization Energy
Kaisa Helttunen,*,† Lauri Lehtovaara,† Hannu Hakkinen,†,‡ and Maija Nissinen†
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†Nanoscience Center, Department of Chemistry, University of Jyvaskyla, P.O. Box 35, FI-40014 Jyvaskyla, Finland
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‡Nanoscience Center, Department of Physics, University of Jyvaskyla, P.O. Box 35, FI-40014 Jyvaskyla, Finland
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̈
S
* Supporting Information
ABSTRACT: The interplay of strong and weak hydrogen
bonds, dipole−dipole interactions, and aromatic interactions of
o- and p-nitroaniline derivatives was studied by combining
crystal structure analysis and density functional theory (DFT)
calculations. Crystal structures of four 2-nitroaniline deriva-
tives, 2-((2-nitrophenyl)amino)ethyl methanesulfonate (1A),
2-((2-nitrophenyl)amino)ethyl 4-methylbenzenesulfonate
(2A), N,N′-((1,3-phenylenebis(oxy))bis(ethane-2,1-diyl))bis-
(2-nitroaniline) (3A), and N-(2-chloroethyl)-2-nitroaniline
(4A), and crystal structures of three 4-nitroaniline derivatives,
2-((4-nitrophenyl)amino)ethyl methanesulfonate (1B), 2-((4-nitrophenyl)amino)ethyl 4-methylbenzenesulfonate (2B), and tert-
butyl-(2-((4-nitrophenyl)amino)ethyl) carbonate (5B), were analyzed with regard to intra- and intermolecular hydrogen
bonding and π−π interactions. The effect of o/p-substitution on π-electron distribution, aromaticity of the nitroaniline ring, and
relative strength of intra- and intermolecular weak interactions were compared using HOMA indices, Hirshfeld surfaces, and
DFT calculations. The 2-nitroaniline derivatives contain an intramolecular hydrogen bond between amino and nitro groups,
creating a six-membered chelate ring, which formed pseudostacked structures with aromatic rings. van der Waals corrected DFT
calculations showed that stacking of a phenyl and a chelate ring contributed significantly to the dimerization of 1A and 2A.
Therefore, it can be concluded that the phenyl−chelate interactions are an important factor in stacking of the monomers in
addition to C−H···O hydrogen bonding. In 4-nitroaniline derivatives, intermolecular N−H···O hydrogen bonds were in a
significant role in packing, creating hydrogen-bonded dimers in 1B and 2B, and hydrogen-bonded chains in 5B.
has been to look for weaker and weaker bonding forces to
increase the understanding of complicated crystal packing and
molecular recognition phenomena. For example, halogen
bonding6 and weak C−H···O hydrogen bonds, where the C−
H group acts as a hydrogen bond donor and oxygen as a
hydrogen bond acceptor,7,8 have been studied and used in
crystal engineering of supramolecular complexes.9 Many of
these compounds have nitrobenzene functionality, since the
oxygen atoms of the nitro group are good acceptors for weak
hydrogen bonds.10 The analysis of crystal structures of
nitrobenzene and nitroaniline compounds reveals the abund-
ancy of these bonds, which, in many cases, are important factors
in crystal packing.11 In addition, nitro groups form dipole−
dipole interactions, which, depending on the geometry, form
mainly by electrostatic interaction between negatively charged
oxygens and positively charged nitrogens,12 or may attain
significant contribution from dispersion forces.13
INTRODUCTION
■
Nitroaromatic compounds are widely used in industrial
production of chemicals, such as explosives, pesticides, dyes,
and pharmaceuticals.1 Nowadays, crystal forms of nitroarenes
and nitroanilines are studied as potential organic nonlinear
optical (NLO) materials.2 The environmental and biological
effects of nitroarenes are significant. Nitroarenes pose toxic and
mutagenic effects for organisms, which are further aggravated
by the long lifetime of nitroarenes in the environment due to
resistance to oxidative attack.3 In addition, biosynthesized
nitroarenes bear important biological activities, for example, as
antibiotics and in signaling.4 In light of recently published data,
these effects may rise from the aromatic interactions of
nitroarenes with proteins.5 Therefore, a detailed understanding
of the chemical nature of nitroarenes and their propensity to
form weak interactions is useful in order to elucidate the
biological activities and toxicity of nitro compounds and to
develope new crystal materials for NLO applications.
In crystal engineering, a complete understanding of weak
intermolecular interactions in a crystal would be optimal for
predicting the exact crystal packing and creating desired
properties for crystalline materials. Over the years, the trend
Received: April 17, 2013
Revised: June 10, 2013
Published: July 1, 2013
© 2013 American Chemical Society
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Aromatic interactions have an important role in self-assembly
and crystal packing of aromatic compounds. The role of π-
stacking, edge-to-face π-stacking, and weaker aliphatic C−H···π
interaction in protein folding and small molecule binding into
proteins has recently been illustrated.5,14 Aromatic interactions
are not easily controlled, and therefore, the theoretical question
about their origin, that is, whether they are governed by
electrostatic or dispersion forces, has been investigated by
computational and experimental methods.15−18 There is strong
evidence that π-stacking is dominated by dispersion forces.15−17
Nevertheless, the electrostatic component may be used to
predict the binding energy.18 Electron density withdrawing
substituents, such as a nitro group, polarize the π-electron cloud
of the benzene ring19 and, consequently, influence the optimal
geometry of the π−π interactions. For example, nitrobenzene
dimers prefer the slipped-parallel (offset face-to-face) orienta-
tion over the T-shaped (edge-to-face) geometry (Figure 1),
which is most stable for benzene dimers.17
strongly coupled, and the planar geometry is mainly caused by a
rotation barrier around the C−N bond or crystal packing.21 On
the other hand, the electron-deficient nitrophenyl ring accepts
more readily the lone pair of the amino substituent, which
enhances the input of the quinonoid structure in the resonance
hybrid of nitroanilines. Also, substitution geometry creates
differences in the electronic structure and aromaticity between
o-, m-, and p-nitroanilines.23 o-Nitroaniline forms an intra-
molecular hydrogen bond between nitro and amino groups,
which creates a six-membered chelate ring further extending the
electron delocalization in the aromatic ring.
During the investigation of new supramolecular resorcinar-
ene hosts,24,25 seven 2-(nitrophenyl)aminoethyl derivatives
were prepared and crystallized. Analysis of the crystal structures
opened up a possibility to compare the effect of ortho (group
A) versus para (group B) subsitution of nitroaniline rings on
weak intra- and intermolecular interactions in crystal packing.
Aniline N−H is the only strong hydrogen bond donor in the
molecules, which formed intramolecular hydrogen-bonded
chelate rings in 1A, 2A, 3A, and 4A, intermolecular hydro-
gen-bonded rings in 1B and 2B, and chains in 5B. In addition
to the nitro groups, derivatives 1A, 1B, 2A, and 2B contain
sulfoxide, and 5B a carbonate group as hydrogen bond
acceptors. The derivatives contain one (1A, 1B, 4A, 5B), two
(2A, 2B), or three (3A) aromatic rings, which creates a
possibility for various intra- and intermolecular π-stacking
geometries. Structures 2A, 3A, and 4A formed intermolecular
parallel displaced π-stacking interactions, 1B parallel and T-
shaped π interactions, and 2B intra- and intermolecular parallel
π-stacking and intermolecular T-shaped π interactions. Instead
of π-stacking, structure 1A formed dimers by the stacking of
chelate and phenyl rings.
Figure 1. Classification of π-stacking geometries. Parameter R1 is
centroid−centroid distance, D is interplanar distance, and S is shift or
centoid−centroid distance projected to a phenyl ring plane. T-shaped
π interaction is also known as edge-to-face, and parallel and slipped
parallel as face-to-face and offset face-to-face π interactions.
In crystal structures, nitro groups are usually coplanar with
the phenyl ring.20 A possible explanation could be resonance
coupling between the nitro group and the aromatic ring, as
indicated in the quinonoid structure (Figure 2). However, the
Crystal packing and intermolecular interactions were
analyzed using Hirshfeld surfaces and fingerprint plots.26
Bond lengths and harmonic oscillation measure for aromaticity
(HOMA)27 were compared in order to elucidate differences
between aromatic interactions of 2- and 4-nitroaniline
derivatives. In addition, density functional theory was applied
to the molecules and their dimers in order to understand how
the substitution affects conformation, the π-stacking geo-
metries, as well as interplay of weak interactions in crystal
packing. Taken together, these methods provide detailed and
quantitative results about molecular conformation, strength of
weak hydrogen bonds, and π-stacking in nitroaniline crystals.
EXPERIMENTAL SECTION
■
Chemicals and solvents were obtained from commercial suppliers
(Sigma-Aldrich and VWR) and used without further purification
unless otherwise noted. Flash chromatography was performed with
Combiflash Companion (Teledyne Isco) and Redisep Gold silica
columns. NMR spectra were recorded with a Bruker Avance DRX
1
(500 MHz for H and 126 MHz for 13C) spectrometer at 30 °C. J
Figure 2. Benzenoid and quinonoid resonance structures for o- and p-
nitroaniline showing intramolecular hydrogen bond of o-nitroaniline
with a dashed bond.
values are given in hertz. ESI-MS spectra were measured with a
Micromass LCT (ESI-TOF) instrument and EI-MS with a VG
AutoSpec instrument using a solid inlet. Melting points were
determined with a Stuart Scientific SMP3 apparatus and are
uncorrected. Elemental analyses were performed on a Vario EL III
instrument.
lack of correlation between C−N bond lengths and coplanarity
of the nitro group does not support this hypothesis.21 In
addition, NMR and computational analysis have shown for
para-substituted nitrobenzenes, such as 4-nitroaniline, that the
nitro group withdraws a constant amount of electron density
from the ring regardless of the presence of electron density
donating substituents.22 These findings suggest that the
resonance of the nitro group and the benzene ring are not
Synthetic Procedures. Preparation of 1A,24 2A,25 2B,28 and 4A29
has been described elsewhere. See the Supporting Information for
details.
2-((4-Nitrophenyl)amino)ethyl Methanesulfonate (1B). p-Nitro-
N-(2-hydroxyethyl)-aniline30 (1.00 g, 5.52 mmol) was dissolved in
pyridine (3 mL), and methanesulfonyl chloride (0.51 mL, 6.59 mmol)
was added dropwise into the solution at 0 °C (in ice bath) under
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nitrogen gas. The mixture was stirred at 0 °C for an additional 1 h, and
2.5 h without an ice bath. Water (50 mL) was added to the mixture.
The yellow-brown precipitate was filtrated with suction and dried
under vacuum. Product was recrystallized from a hot chloroform−
acetone−hexane solution to provide yellow crystals; yield 1.08 g
the C temperature factor) and refined as riding atoms, except for
amine hydrogens, which were located from the Q-peaks and restrained
using DFIX 0.91. Crystal structure analysis and figures were prepared
using Mercury CSD 3.0,34 and Olex2. Hirshfeld surfaces (plotted
against dnorm, curvature and shape index) and 2D fingerprint plots were
calculated using CrystalExplorer.35 Crystallographic data (excluding
structure factors) for the structures in this paper have been deposited
with the Cambridge Structural Data Center as supplementary
publication nos. CCDC 930277−930283.
Powder X-ray Diffraction. PXRD patterns of the nitroaniline
derivatives were measured after recrystallization from chloroform−
hexane solution using a PANalytical X’Pert Pro system in a reflection
mode with monochromatized CuKα radiation (λ = 1.54178 Å) at
ambient temperature.
Computational. DFT calculations were performed using Turbo-
mole program V6.4.36,37 The PBE exchange-correlation functional38
with Grimme’s van der Waals corrections39 as implemented in
Turbomole V6.4 were used. All calculations were performed with the
aug-cc-pVDZ basis.40 The ground-state geometries were fully
optimized for 1A, 1B, 2A, 2B, and N-ethyl-2-nitroaniline using
crystallographic coordinates for isolated monomers and dimers as a
starting point.
1
(75%). mp 136−138 °C. H NMR (CDCl3, 500 MHz): 3.05 (s, 3H;
3
3
CH3), 3.62 (t, J (H,H) = 5.2 Hz, 2H; CH2), 4.44 (t, J (H,H) = 5.2
3
3
Hz, 2H; CH2), 6.60 (dt, J (H,H) = 9.2 Hz, 2H; ArH), 8.12 (dt, J
(H,H) = 9.2 Hz, 2H; ArH) ppm. 13C NMR (CDCl3, 126 MHz): 37.9,
42.8, 67.2, 111.6, 126.6, 139.2, 152.4 ppm. Anal. Calcd for
C9H12N2O5S: C, 41.53; H, 4.65; N, 10.76. Found: C, 41.53; H,
4.82; N, 10.84. m/z (EI) 260 M+.
N,N′-((1,3-Phenylenebis(oxy))bis(ethane-2,1-diyl))bis(2-nitro-
aniline) (3A). A mixture of resorcinol (0.21 g, 1.89 mmol), Cs2CO3
(1.30 g, 4.00 mmol dried at 120 °C), dibenzo-18-crown-6 (0.14 g, 0.40
mmol), and dry acetonitrile (25 mL) was refluxed for 1 h under
nitrogen. A solution of 2-((2-nitrophenyl)amino)ethyl 4-methylben-
zenesulfonate 2A (1.23 g, 3.67 mmol) in 10 mL of dry acetonitrile was
added dropwise, and the mixture was refluxed for 2 days. The dark
brown mixture was filtrated, and the solvent was distilled off under
vacuum. The orange precipitate was dissolved in 70 mL of CHCl3,
washed four times with water, and dried with MgSO4. The product
was purified using flash chromatography (SiO2, CHCl3 eluent with a
gradient of 0−10% MeOH containing 0.25% triethylamine).
Recrystallization from a hot chloroform solution using hexane as an
antisolvent provided orange crystals with 33% yield (0.28 g). mp
156.5−157 °C. 1H NMR (CDCl3, 500 MHz): 3.73 (q, 3J (H,H) = 5.5
Hz, 4H; CH2), 4.23 (t, 3J (H,H) = 5.5 Hz, 4H; CH2), 6.54 (t, 4J (H,H)
= 2.3 Hz, 1H; ArH), 6.57 (dd, 3J (H,H) = 8.2 Hz, 4J (H,H) = 2.4, 2H;
RESULTS AND DISCUSSION
■
Four 2-(2-nitrophenyl)aminoethyl derivatives (1A, 2A, 3A, 4A)
and three 2-(4-nitrophenyl)aminoethyl derivatives (1B, 2B,
5B) were prepared by nucleophilic substitution using standard
synthetic methods (Figure 3). Compounds 1A, 1B, 2A, and 2B
3
ArH), 6.68 (m, 2H; ArH), 6.93 (dd, J (H,H) = 8.7 Hz, 2H), 7.20 (t,
3J (H,H) = 8.2 Hz, 1H; ArH), 7.46 (m, 2H), 8.19 (dd, 3J (H,H) = 8.6
Hz, 2H; ArH), 8.31 (s, br, 2H; NH) ppm. 13C NMR (CDCl3, 126
MHz): 42.5, 66.3, 102.3, 107.9, 113.8, 115.9, 127.2, 130.3, 132.6,
136.3, 145.4, 159.8 ppm. Anal. Calcd for C22H22N4O6·0.55H2O: C,
59.94; H, 5.19; N, 12.50. Found: C, 58.58, H, 4.80; N, 12.66. m/z
(ESI-TOF) 461 (M + Na+), 477 (M + K+).
tert-Butyl-(2-((4-nitrophenyl)amino)ethyl) Carbonate (5B). p-
Nitro-N-(2-hydroxyethyl)-aniline (0.27 g, 1.49 mmol) was dissolved
in dry acetone (5 mL) under nitrogen gas. Di-tert-butyl dicarbonate
(0.7 mL, 3.05 mmol) was added to the solution. The mixture was
heated to 50 °C and stirred for 20 h. At this stage, only starting
material was present in TLC (SiO2, 99:1 CHCl3:MeOH), whereupon
more di-tert-butyl dicarbonate (0.7 mL, 3.05 mmol) was added. After
48 h of stirring at 50 °C and 3 days at room temperature, solvent was
distilled off under vacuum and the yellow residue was purified with
flash chromatography to remove the excess dicarbonate (SiO2,
CHCl3−MeOH 99:1). Recrystallization from a hot chloroform
solution using hexane as an antisolvent provided yellow block crystals
1
with 34% yield (0.14 g). mp 144−145 °C. H NMR (CDCl3, 500
MHz): 1.49 (s, 9H; CH3), 3.51 (t, 3J (H,H) = 5.3 Hz, 2H; CH2), 4.30
3
3
(t, J (H,H) = 5.3 Hz, 2H; CH2), 4.83 (s, br, 1H; NH), 6.56 (dt, J
3
(H,H) = 9.3 Hz, 2H; ArH), 8.09 (dt, J (H,H) = 9.3 Hz, 2H; ArH)
ppm. 13C NMR (CDCl3, 126 MHz): 27.9, 42.7, 64.9, 83.2, 111.4,
126.5, 138.8, 152.9, 153.6 ppm. Anal. Calcd for C13H18N2O5: C, 55.31;
H, 6.43; N, 9.92. Found: C, 55.09; H, 6.36; N, 10.03. m/z (EI) 282
M+.
Single-Crystal X-ray Diffraction. Crystals of 1A and 2A were
grown in CHCl3 solution with hexane diffusion. Crystals of 1B, 2B,
and 3A were grown in an NMR tube in CDCl3 solution. Crystals of 4A
and 5B were obtained directly from the recrystallization in
chloroform−hexane solution.
Single-crystal X-ray data were recorded on a Nonius Kappa CCD
diffractometer with an Apex II detector using graphite monochrom-
atized CuKα (λ = 1.54178 Å) radiation at a temperature of 173 K. The
data were processed, and absorption correction was made to all
structures with Denzo-SMN v.0.97.638.31 The structures were solved
by direct methods (SHELXS-97) and refined (SHELXL-97) against F2
by full-matrix least-squares techniques using the SHELX-97 software
package32 and Olex2.33 The hydrogen atoms were calculated to their
idealized positions with isotropic temperature factors (1.2 or 1.5 times
Figure 3. Nitroarene derivatives 1A−5B. Group A compounds have a
2-nitroaniline ring and an intramolecular N−H···O hydrogen bond
(dashed bond); group B contains 4-nitroaniline derivatives.
have a sulfonyloxy group connected to the ethyl linker. Since
1A and 1B are ortho and para isomers of 2-((nitrophenyl)-
amino)ethyl methanesulfonate, comparison of their crystal
structures reveals the effect of o/p-substitution on intra- and
intermolecular weak interactions. The competing interactions
are intra- and intermolecular strong hydrogen bonds from the
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Table 1. Crystal Data and Refinement Parameters
parameter
composition
1A
1B
2A
2B
C9H12N2O5S
260.27
C9H12N2O5S
260.27
C15H16N2O5S
336.36
C15H16N2O5S
336.36
FW
crystal system
space group
a/Å
monoclinic
P21/c
monoclinic
P21/c
monoclinic
P21/c
monoclinic
P21/c
6.791(6)
13.527(4)
12.462(2)
98.507(14)
1132.1(11)
4
13.1886(2)
10.2790(1)
8.3635(1)
97.1700(1)
1124.94(2)
4
7.9887(4)
27.077(2)
7.0718(5)
94.729(5)
1524.5(2)
4
9.2567(1)
18.5024(2)
9.7785(1)
113.6710(1)
1533.87(3)
4
b/Å
c/Å
β/deg
volume /Å3
Z
D
calcd/Mg·m−3
1.527
1.537
1.466
1.457
F(000)
μ/mm−1
544
544
704
704
2.704
2.721
2.150
2.137
crystal size/mm
meas. reflns
0.40 × 0.24 × 0.10
5800
0.15 × 0.10 × 0.05
2884
0.24 × 0.18 × 0.10
3944
0.40 × 0.20 × 0.20
4714
indep. reflns
Rint
1980
1895
2630
2626
0.0592
0.0688
0.0306
0.0514
R1 [I > 2σ(I)]
wR2 [I > 2σ(I)]
R1 (all data)
wR2 (all data)
GOOF on F2
largest diff. peak and hole/e Å−3
0.0352
0.0584
0.0404
0.0491
0.0902
0.1533
0.1007
0.1270
0.0387
0.0749
0.0498
0.0604
0.0930
0.1629
0.1070
0.1359
1.048
1.148
1.049
1.052
0.34, −0.32
0.44, −0.34
0.25, −0.29
0.26, −0.47
Table 2. Crystal Data and Refinement Parameters
parameter
3A
4A
5B
composition
FW
C22H22N4O6
438.44
C8H9ClN2O2
200.62
C13H18N2O5
282.29
crystal system
space group
a /Å
monoclinic
C2/c
monoclinic
P21/c
monoclinic
P21/c
14.6336(2)
7.2215(1)
19.5363(2)
105.2750(1)
1991.59(4))
1.462
7.2248(1)
16.2084(2)
7.5660(1)
94.4680(1)
883.30(2)
1.509
11.9007(1)
16.0041(2)
7.3763(1)
94.3870(1)
1400.77(3)
1.339
b/Å
c/Å
β/deg
volume /Å3
D
Z
calcd/Mg·m−3
4
4
4
F(000)
μ /mm−1
920
416
600
0.905
3.586
0.870
crystal size/mm
meas. reflns
0.50 × 0.30 × 0.10
2621
0.25 × 0.15 × 0.10
2338
0.25 × 0.20 × 0.15
3944
indep. reflns
1749
1508
2402
Rint
0.0337
0.0341
0.0689
R1 [I > 2σ(I)]
wR2 [I > 2σ(I)]
R1 (all data)
wR2 (all data)
GOOF on F2
largest diff. peak and hole/e Å−3
0.0392
0.0415
0.0572
0.1011
0.1080
0.1522
0.0446
0.0464
0.0673
0.1053
0.1124
0.1614
1.057
1.065
1.043
0.17, −0.23
0.19, −0.28
0.22, −0.29
amino group, weak hydrogen bonds from aryl and alkyl C−H
to nitro or sulfonyl oxygens, dipole−dipole interactions
between nitro groups, and aromatic interactions between the
nitroaniline rings. Compounds 2A and 2B contain an aromatic
p-toluenesulfonyl group, which increases the possibilities for
intra- and intermolecular aromatic interactions. Compound 3A,
N,N′-((1,3-phenylenebis(oxy))-bis(ethane-2,1-diyl))bis(2-
nitroaniline), has two 2-(2-nitrophenyl)aminoethyl groups
connected to a resorcinol ring, which reduces the number of
available hydrogen bond acceptors and increases the number of
aromatic rings. Compound 4A, N-(2-chloroethyl)-2-nitroani-
line, contains an ethyl chloride group, which induces C−H···Cl
hydrogen bonds and affects the acidity of −CH2Cl protons.
Compound 5B, tert-butyl (2-((4-nitrophenyl)amino)ethyl)
carbonate, contains a tert-butoxy carbonyloxy group in the 2-
aminoethyl chain, which increases the ratio of aliphatic groups
in the structure.
Crystal Structures. The nitroaniline derivatives crystallized
readily as yellow or orange crystals from chloroform or
chloroform−hexane solution. Crystal structures of 1A−5B were
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solved by single-crystal X-ray diffraction (Tables 1 and 2).
Powder X-ray diffraction patterns of the compounds were
recorded to ensure that the single crystal structure was a good
representative for the sample.41
The conformation of the nitroaniline ring in all derivatives
was close to planar. The nitro group tilt angle from the phenyl
ring plane was 2.9° in 1A, 7.8° in 2A, 4.5° in 3A, and 5.7° in
4A. In 4-nitroaniline derivatives, the nitro group tilt was
smaller, 0.7° in 1B, 3.3° in 2B, and 1.4° in 5B. Visual inspection
of the structures revealed that the small inclination of the nitro
group is caused in most cases by weak hydrogen bonds to nitro
oxygens, such as in 2A, 2B, 3A, and 4A.
The amino nitrogen resides coplanary to the phenyl ring
(1.5−7.9° tilt), which denotes an sp2 hybridization. The torsion
of the amino group hydrogen against the CC bond of the
aromatic ring (CC−N−H torsion) varies between 1.4° and
8.4°. In 2B, however, a larger torsion angle of −19.5° was
observed, resulting from the intermolecular hydrogen bond to
the sulfonyl oxygen.
Figure 5. Crystal structure of 3A showing intramolecular S11(6)
hydrogen bond and weak C−H···O hydrogen bond to nitro oxygen
(H8B···O12 = 2.67 Å, 163°); thermal ellipsoids at 50% probability.
All 2-nitroaniline derivatives (A) formed an intramolecular
S11(6) N−H···O−N hydrogen bond,42 in which the D···A
distance is 2.62−2.63 Å (Figures 4−6). The 4-nitroaniline
Figure 6. Crystal structure of 4A formed dimers by weak C−H···O
hydrogen bonds to nitro oxygens: H8A···O2 = 2.57 Å, 148°; H8A···O1
= 2.71 Å, 144°; H3···O2 = 2.54 Å, 131°. Thermal ellipsoids at 50%
probability; Cl···H contacts not shown.
C···H, H···H, and O···H contacts (Figure 9) revealed the
influence of aromatic face-to-face stacking, aromatic edge-to-
face stacking, dispersion forces, and hydrogen bonds to the
crystal packing. In 1A, only 0.5% of the surface area is involved
in C···C contacts, indicating the lack of aromatic face-to-face
stacking. Instead, hydrogen bonds cover almost half of the
surface area (48.4%), being the most significant contributor to
the crystal packing. The fingerprint plots (Figure 10) show the
contribution and bond distances and O···H contacts in 1A, 1B,
2A, and 2B. The most prominent features of 2A are the
proportion of C···C contacts (9.1%) and a narrow shape of the
fingerprint plot, indicating the importance of π-stacking and the
lack of edge-to-face π interactions in crystal packing. The
Hirshfeld surface of 3A contains a significant proportion of
C···H contacts (16%) resulting from aliphatic C−H···π
interactions, whereas the role of aromatic interactions (C···C
contacts 5.3%) is relatively small in comparison to nitroaniline
derivatives with only one or two aromatic rings. Structure 4A
contains a significant proportion of Cl···H contacts (17.9%). In
addition, the O···H contacts play a significant role in packing,
since the number of O···H contacts per oxygen is high, even
though the total surface area occupied by O···H contacts is
relatively low in comparison to other compounds (28.7%). In
5B, the proportion of H···H contacts is larger than that in the
other structures due to input of the tert-butyl group to the
aliphatic dispersion forces.
Figure 4. Crystal structures of 1A (top) and 2A (bottom) showing
intramolecular S11(6) hydrogen bond and weak C−H···O hydrogen
bonds to nitro oxygens (H5···O1 = 2.52 Å, 164°; H8A···O2 = 2.62 Å,
137°); thermal ellipsoids at 50% probability. Weak hydrogen bonds to
sulfonyl oxygens not shown.
derivatives 1B and 2B (Figure 7) formed hydrogen-bonded
R22(14) dimers between amino hydrogens and sulfonyl oxygens.
Compound 5B, which does not contain a sulfonyloxy group,
formed a hydrogen-bonded C11(7) chain between amino
hydrogen and nitro oxygen (Figure 8).
Weak hydrogen bonds for nitro oxygens affect the crystal
packing of 1B, 2B, and 4A. A bifurcated C−H···O bond, which
is a relatively common hydrogen-bonding pattern in nitro
compounds,43 connects molecules of 1B in chains and
molecules of 4A in dimer pairs.
The proportion of different short contacts within each crystal
was compared using Hirshfeld surfaces and decomposed
fingerprint plots. The relative surface area covered by C···C,
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Figure 9. Short contact distribution of Hirshfeld surfaces.
Figure 7. Crystal structures of 1B (top) and 2B (bottom) formed
hydrogen-bonded R22(14) dimers. Selected hydrogen bonds for 1B:
N1···O2 = 2.99 Å, ∠DHA 171°; H1C···O4 = 2.70 Å, 133°; H1C···O5
= 2.61 Å, 166°. For 2B: N1···O2 = 2.99 Å, 159°. Thermal ellipsoids
drawn at 50% probability; weak hydrogen bonds to sulfonyl oxygens
not shown.
Figure 10. Hirshfeld surface of 1A plotted against (A) dnorm (red color
indicates contacts shorter than vdW distance) and (B) shape index;
arrows point to complementary patches. Fingerprint plots of 1A, 1B,
2A, and 2B showing O···H contacts in color.
Figure 8. Crystal packing of 5B showing C11(7) hydrogen bond pattern
between amino and nitro groups (N1···O4 = 3.17 Å, 152°), H12···O1
contact (2.54 Å, 154°), and dipole−dipole interaction (N2···O4 = 3.35
Å, N2···O5 = 3.52 Å). Thermal ellipsoids drawn at 50% probability.
4A formed an aromatic interaction between two 2-nitroaniline
rings, again with an antiparallel orientation of the nitro and
amino substituents.
1A and 5B did not form aromatic interactions in a
conventional geometry. In 1A, the aromatic rings align as
sheets, and on the one side, the geometry seems favorable to
dipole−dipole interaction between two nitro groups (Figure
13). On the other side, however, the Hirshfeld surface indicates
flat and shape complementary areas between an aromatic ring
of one molecule and a hydrogen-bonded chelate ring of the
other (Figure 10). The distance between the phenyl ring
centroids, R1, is too long for an aromatic interaction, whereas
the distance between the centroid of the chelate ring and the
centroid of the phenyl ring (R2) is within bonding distance
(first entry in Table 3). In 5B, the N−H group lies on top of
the aromatic ring but the geometry does not remind of an
aromatic interaction, and overall, the position of the nitroani-
line rings is more likely directed by the pairs of dipole−dipole
interactions between the nitro groups (Figure 8).
Most of the nitroaniline derivatives formed at least one
aromatic π-stacking interaction (Table 3). Compound 1B
formed a parallel π interaction between two opposing
molecules, and a T-shaped π interaction to a π-stacked dimer
above and below. Compound 2A obtained a steplike
conformation and formed continuous displaced parallel π
stacks of tolyl rings, and separate stacks for 2-nitroaniline rings
(Figure 11). As in 1B, the nitro and amino groups in the π
stacks are aligned in an antiparallel fashion. Compound 2B
adopted a cliplike conformation, in which the tolyl and 4-
nitroaniline rings formed an intramolecular π stack. The tolyl
rings of two molecules further stacked in a displaced parallel
geometry, and the 4-nitroaniline rings formed an edge-to-face π
interaction, in which a short contact between aryl C−H and
nitro O5 has a significant role (Figure 12). Compounds 3A and
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HOMA1 indices calculated for the DFT-optimized structures of
1A, 1B, 2A, and 2B. In addition, the HOMA index for the
hydrogen-bonded chelate ring in o-nitroaniline has previously
been reported to be 0.59.23 Similar calculation for group A
derivatives gave a mean HOMA index for the chelate ring of
0.67. In comparison to o-nitroaniline, the aromaticity of the
chelate ring was slightly increased, which probably results from
the inductive effect of the N-ethyl substituent.
Table 3. π−π Stacking Geometries in Nitroaniline
a
Derivatives
structure angle/deg D/Å
R1/Å R2/Å
S/Å
contact
1A
1B
2A
2A
2A
0.0
0.0
0.0
0.0
1.6
3.34
3.51
3.44
3.43
3.45
4.97
3.53
3.84
3.78
3.63
3.63
1.44 C1−C6···C1−C6 (1 −
x, 1 − y, −z)
0.44 C4−C9···C4−C9 (−x,
−y, −z)
1.70 C1−C6···C1−C6 (−x,
1 − y, 1 − z)
1.59 C1−C6···C1−C6 (−x,
1 − y, 2 − z)
3.53
3.83
Recently, crystal structures of Schiff base salicylidene ligands,
suggesting a π-stacking interaction between a pseudoaromatic
ring formed through intramolecular hydrogen bonding and
ordinary aromatic ring, have been published.46,47 The chelate
ring of 2-nitroaniline derivatives also shows aromatic character
based on the HOMA indices, even though the hydrogen-
bonded system is different, lacking keto−enol tautomerism.
Table 3 indicates that π stacks of 2-nitroanilines contain shorter
interplanar distances (D = 3.33−3.44 Å) than 4-nitroanilines
(D = 3.50−3.51 Å). In addition, the shortest interplanar
distances, D < 3.40 Å, were connected with the longest
centroid−centroid distances, R1 > 4 Å, and the shortest phenyl
and chelate centroid−centroid distances, R2 < 3.70 Å, that is,
stacking of the phenyl and chelate rings. A search of crystal
structures in CSD revealed that the stacking of phenyl and
chelate rings is present in many 2-nitroaniline compounds.48
Considering the π-stacking geometries of 2-nitroaniline
derivatives, especially in 1A, and the aromatic character of the
chelate ring, the interaction between the phenyl ring and the
hydrogen-bonded chelate ring was investigated using density
functional theory calculations.
1.12 C9−C14···C9−C14
(x, 1/2 − y, −1/2 +
z)
2A
1.6
3.48
3.63
1.04 C9−C14···C9−C14
(x, 1/2 − y, 1/2 + z)
2B
2B
11.0
0.0
3.69
3.50
3.85
3.93
1.10 C2−C7···C10−C15
1.78 C2−C7···C2−C7 (1 −
x, −y, 1 − z)
3A
0.0
3.38
3.51
3.67
0.95 C1−C6···C1−C6 (1/2
− x, −1/2 − y, 1 −
z)
3A
4A
0.0
0.0
3.30
3.41
4.71
3.98
3.59
3.55
1.23 C1−C6···C1−C6 (1/2
− x, 1/2 − y, 1 − z)
2.06 C1−C6···C1−C6 (−x,
1 − y, 1 − z)
a
R1, R2 = centroid−centroid distances; D = interplanar distance; S =
shift.
Aromaticity of the Nitroaniline Rings. The substituent
effects on the electron delocalization of the nitroaniline rings
were analyzed by comparing C−C and C−N bond lengths. The
C−NO2 bond length was 1.44−1.45 Å for all derivatives, close
to a typical C−N bond length for a nitro substituent in a crystal
structure, 1.47 Å.44 The C−NH bond lengths were 1.35−1.37
Å, which correspond to a C−N bond to a planar sp2 nitrogen,
showing that the amino nitrogen donates its lone pair to the
aromatic π-electron system.
The aromaticity of the nitroaniline rings was compared using
C−C bond lengths to calculate harmonic oscillation measure of
aromaticity (HOMA) indices.27 The HOMA index is calculated
by summing the deviation of the observed bond lengths from
ideal bond lengths (Ropt) and scaling the result to give HOMA
DFT Calculations. Ground-state energies and optimized
geometries were calculated for compounds 1A, 1B, 2A, and 2B
starting from the crystal structure coordinates for isolated
monomers and dimers in the gas phase.
The optimized geometries of 1A, 2A, and 2B monomers
were very close to the conformation in the crystal structure,
indicating that monomers are in a relaxed conformation. In
contrast, the optimized geometry of 4-nitroaniline monomer
1B deviates from the crystal structure, indicating that
intermolecular interactions are required for sustaining the
observed conformation. In the crystal structure, the con-
formation of 1B is linear and the monomers are connected into
a hydrogen-bonded R22(14) dimer. When the 1B monomer was
relaxed with DFT, it formed an intramolecular N−H···O
hydrogen bond to the sulfonyl oxygen. However, when the 1B
dimer was relaxed with DFT, the intermolecular hydrogen
bonds were re-established, and a dimerization energy of −0.31
eV was obtained. Thus, intermolecular hydrogen bonds are
stronger and likely improve the crystal packing into a regular
́
= 0 for a Kekule type of structure and HOMA = 1 for a
completely delocalized structure with all bonds equal to Ropt
=
1.388 Å.45 The 2-nitroaniline derivatives had a slight decrease in
aromaticity in comparison to the 4-nitroaniline derivatives. The
mean of HOMA index for 2-nitroaniline derivatives was 0.88
and, for 4-nitroaniline derivatives, 0.93 (Table 4). Similar values
have previously been obtained for o- and p-nitroaniline, 0.86
and 0.93, respectively,23 and these values were close to the
Figure 11. Aromatic interactions in crystal packing of 2A shown as a stick (left) and a space-filling presentation (right, hydrogens omitted for
clarity). H2···O4 = 2.62 Å, 149°.
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Figure 12. Crystal packing of 2B as a stick (left) and a space-filling presentation (right, hydrogens omitted for clarity) showing aromatic interactions
and hydrogen bonds. H9B···O5 = 2.49 Å, 150°; H8A···O4 = 2.62 Å, 129°; H14···O5 = 2.56 Å, 152°; H12···O1 = 2.58 Å, 125°.
Figure 13. Crystal packing of 1A showing weak hydrogen bonds, dipole−dipole interaction between O1 and N1 (3.38 Å), and phenyl and chelate
ring stacking (R2 = 3.63 Å).
from aryl H3 to sulfonyl O5, and the proposed phenyl−chelate
stacking interaction. The effect of weak hydrogen bonds on
dimerization was eliminated by repeating optimization for a N-
ethyl-2-nitroaniline dimer, which lacks the hydrogen bond
acceptors. The dimerization energy for the relaxed structure is
−0.62 eV. However, the stacking geometry is different than that
for the 1A dimer. Therefore, we extracted a stacking geometry
closely resembling the stacking geometry of the 1A dimer from
the geometry optimization path. This structure has a
dimerization energy of −0.53 eV. The energy difference of
0.09 eV between this partially relaxed structure and the optimal
structure can be easily overcome by the hydrogen bonds.
Moreover, the crystal structure and DFT-optimized geometry
of 2A with a dimerization energy of −0.65 eV is actually quite
close to the fully relaxed structure of the N-ethyl-2-nitroaniline
dimer. Thus, it can be concluded that there is a binding
interaction between the phenyl and the chelate rings, which
contributes significantly to stabilization of the 1A and 2A
crystals.
Table 4. HOMA Indices for Crystal Structures and DFT-
Optimized Structures of Nitroaniline Derivatives (HOMA1
= Phenyl Ring, HOMA2 = Chelate Ring)
structure
HOMA1
HOMA2
0.626
HOMA1 (DFT)
HOMA2 (DFT)
0.573
1A
1B
2A
2B
3A
4A
5B
0.912
0.934
0.877
0.936
0.866
0.859
0.920
0.891
0.947
0.832
0.914
0.661
0.527
0.687
0.686
structure, whereas intramolecular hydrogen bonds may be
weakened by molecular strain.
Although the 2B monomers are nearly relaxed in the crystal,
intermolecular hydrogen bonding and π-stacking stabilize the
crystal. On the basis of DFT geometry optimizations, the
dimerization energy of R22(14) hydrogen-bonded 2B monomers
is −0.87 eV, and the dimerization energy of intermolecular
tosyl−tosyl π-stacked 2B monomers is −0.55 eV.
To calculate the interaction energy for phenyl−chelate
stacking, a dimer of 1A molecules was relaxed starting from
the crystal structure coordinates. The optimized geometry for
the 1A dimer is very similar to the original crystal structure
geometry (Figure 14), having a dimerization energy of −0.81
eV. The dimer is held together by two weak hydrogen bonds
CONCLUSION
■
The effect of o/p-substitution on intra- and intermolecular
hydrogen bonds, dipole−dipole interactions, and aromatic
interactions in nitroaniline derivatives was investigated using
crystal structure analysis and DFT calculations. Nitro and
amino functionalities were approximately coplanar with the
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Figure 14. DFT-optimized structures for 1A dimer and N-ethyl-2-nitroaniline dimer. Top view of XRD structure and DFT structures.
phenyl ring. The 2-nitroaniline derivatives formed an intra-
molecular hydrogen bond between amino and nitro groups,
creating a six-membered chelate ring, whereas, in 4-nitroaniline
derivatives, the amino hydrogen is sterically available for
intermolecular hydrogen bonding. 4-Nitroaniline derivatives 1B
and 2B, which contain sulfonyloxy groups, formed N−H···O
hydrogen-bonded dimers. DFT calculations indicated that the
hydrogen-bonded dimer is more stable than an intramolecular
hydrogen bond by −0.31 eV for 1B and −0.87 eV for 2B. In
addition to strong hydrogen bonds, C−H···O hydrogen bonds
into sulfonyl oxygens and nitro oxygens were important in
crystal packing for most derivatives, especially in 1A, 1B, 2A,
2B, and 4A. Dipole−dipole interactions between nitro groups
were in a minor role, and found only in structures 1A and 5B.
Differences in the shape and electron distribution between 2-
and 4-nitroaniline rings create variation in π-stacking geo-
metries. 2-Nitroaniline derivatives had a slightly lower
aromaticity than 4-nitroaniline derivatives based on the
HOMA indices. In 4-nitroaniline derivatives, parallel and T-
shaped π interactions were observed, whereas, in 2-nitroaniline
derivatives, parallel displaced π-stacking and phenyl−chelate
stacking were abundant. Closer investigation of the 2-
nitroaniline derivatives 1A and 2A using DFT revealed that
stacking of a phenyl and a chelate ring formed a weakly bonded
dimer, in which phenyl−chelate stacking contributed signifi-
cantly to the dimerization energy. Thus, phenyl−chelate
stacking may be regarded as a complementary interaction to
phenyl−phenyl stacking, which affects the crystal packing of 2-
nitroaniline derivatives.
ACKNOWLEDGMENTS
■
The Emil Aaltonen Foundation and the Academy of Finland
(project 21000019111) are acknowledged for funding. Ms.
Mirja Lahtipera is acknowledged for measuring the EI-MS
̈
spectra and Mr. Reijo Kauppinen for measuring the NMR
spectra. Dr. Elisa Nauha is thanked for assistance with the XRD.
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ASSOCIATED CONTENT
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S
* Supporting Information
NMR spectra and synthetic procedures, PXRD patterns,
crystallographic tables, and figures for DFT-optimized
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Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kaisa.j.helttunen@jyu.fi.
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