Structural investigation of weak intermolecular interactions in fluorine substituted isomeric N-benzylideneanilines

Article abstract of DOI:10.1021/cg3010294

The study of the influence of aromatic C-F group in directing crystal packing is an important area of current research. The role of the aromatic C-F group in the formation of weak intermolecular interactions in the absence of strong hydrogen bond donors a

Full text of DOI:10.1021/cg3010294

Article
pubs.acs.org/crystal
Structural Investigation of Weak Intermolecular Interactions
in Fluorine Substituted Isomeric N‑Benzylideneanilines
Published as part of the Crystal Growth & Design virtual special issue In Honor of Prof. G. R. Desiraju
Gurpreet Kaur,†,# Piyush Panini,‡,# Deepak Chopra,*,‡ and Angshuman Roy Choudhury*,†
†Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, Knowledge City,
S. A. S. Nagar, Manauli PO, Mohali, 140306, Punjab, India
‡Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Govindpura, Bhopal, 462023,
Madhya Predesh, India
S
* Supporting Information
ABSTRACT: The study of the influence of aromatic C−F
group in directing crystal packing is an important area of
current research. The role of the aromatic C−F group in the
formation of weak intermolecular interactions in the absence of
strong hydrogen bond donors and acceptors has been analyzed in
a series of 15 newly synthesized fluorine substituted (mono- and
di-) isomeric N-benzylideneanilines. It was observed that five
compounds (out of a total number of 15) were liquids at room
temperature, while others have low melting points (<60 °C). In situ crystallization, using an optical heating and crystallization device
(OHCD), has been used to crystallize and determine the crystal structures of three out of five compounds which were found to be
liquids at 25 °C. A detailed investigation of the molecular conformation and the crystal packing in these compounds reveals that the
presence of organic fluorine acts as a significant contributor in the construction of various supramolecular synthons, essentially using a
variety of C−H···F intermolecular interactions. These have been found to generate different three-dimensional arrangements of
molecules in the crystalline framework. In order to realize the stabilizing influence exerted by such weak interactions, intermolecular
C−H···F interaction energies have been calculated using Firefly to quantify the strength of such interactions. Lattice energy calculations
have been performed and the individual energies, namely, the Coulombic, polarization, dispersion, and repulsive contributions to the
lattice energy have been determined using the CLP program. In addition to these, theoretical calculations have been performed at
the density functional theory level, and the experimental geometry has been compared with the optimized geometry to highlight the
importance of molecular conformation in the solid and gas phase. It is of interest to note that stabilization resulting from the presence
of C−H···F interactions, albeit less, is not negligible and does contribute toward crystal packing.
importance of organic fluorine in the crystal engineering com-
munity. It was realized that, in the absence of strong hydrogen
bonds, the molecules containing C−F bond essentially pack
utilizing weak C−H···F, C−F···π, and C−F···F−C interac-
tions.7 The focus was then shifted toward analyzing the
presence of such weak interactions in the presence of strong
H-bonds. In this regard, detailed crystallographic investigations
have recently been performed on fluorinated,8a−c other halogen
substituted,8d and also trifluoromethylated8e benzanilides
containing a strong N−H donor and a strong acceptor such
as >CO group. It was observed that in addition to the well
documented N−H···OC and C−H···OC hydrogen bonds,
the crystal packing was influenced by weak interactions of
the type C−H···F−C along with C−F···π, C−F···F−C, and
C−H···π intermolecular contacts in the crystal lattice. In order
to evaluate the support provided by weak interactions involving
INTRODUCTION AND AIM OF STUDY
■
The study of intermolecular noncovalent interactions has been
a major theme of contemporary research to study the formation
of supramolecular assemblies.1 Various noncovalent interac-
tions are well recognized in chemistry and biology.2 Strong
hydrogen bonds have been well understood in the literature,3
and the recent focus is toward understanding the role of weak
hydrogen bonds in building supramolecular assemblies of small
organic molecules.4 In recent years, the focus has been ex-
tended toward the understanding of intermolecular interactions
involving halogens, particularly in the context of organic fluo-
rine.5a A C−F group, historically termed as “organic fluorine”,5b
has been shown to exhibit poor hydrogen bond acceptor
properties in the literature.5c,d The absence of participation of
organic fluorine in intermolecular interactions has been attri-
buted to the nonpolarizable nature of the fluorine atom.5e The
importance of intermolecular interactions involving organic
fluorine has received considerable attention and significant
progress has been made in the past decade. A recent review,6a
a highlight,6b and a perspective6c have brought out the
Received: July 21, 2012
Revised: August 30, 2012
Published: September 4, 2012
© 2012 American Chemical Society
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organic fluorine, we have synthesized and crystallized a series
of isomeric N-benzylideneanilines wherein the amide group
has been replaced by an imine functional group, keeping the
remaining molecular scaffold invariant when compared to
fluorinated benzanilides. This eliminates the possibility of the
formation of strong hydrogen bonds and allows one to assess
the interplay of other weak interactions in the crystalline solid.
The N-benzylideneanilines are an important class of com-
pounds and have important biological properties. A number of
patents highlight the versatile application of this class of mol-
ecules, for example, in the protection of skin against the harmful
effects of sunlight (erythema) on human skin9a and warm-blooded
animals.9b A recent patent highlights the importance of a mixture
of N-benzylideneaniline compounds with aqueous acid solution
being used as corrosion inhibitor.9c
model system containing organic fluorine. It has been documented
that the presence of fluorine in the ortho or meta position of
different aromatic molecules generates positional disorder due to
their participation in different intermolecular interactions, thus
providing stability to the crystal lattice.7a,19 In the current series,
the fluorine atom in the ortho and the meta positions may also get
disordered in order to offer different intermolecular interactions
and hence generate different molecular and crystal structures. The
purpose is to access the different independent conformations a
given molecule can explore (phenomenon of conformational poly-
morphism) and to understand the nature of disorder (static or
dynamic) present in different fluorine substituted compounds.
Furthermore, it is of interest to understand the nature and
the strength of C−H···F interactions, in fluorine substituted
N-benzylideneanilines. Fifteen new compounds (Scheme 1) were
In the crystallographic literature, these compounds have a
rich history. The initial structural determination was done in
1968.10a It was observed that the unsubstituted N-benzylide-
neaniline (parent compound) is nonplanar and the aniline ring
is twisted by 57° from the C−NC−C plane. It was observed
that the UV spectra of this compound10b was different from that
of stilbene10c and trans-azobenzene10d,e whose crystal struc-
ture revealed that those molecules were planar. The crystal struc-
ture of N-benzylideneaniline was again redetermined using accu-
rate data.11 In order to account for the nonplanar conformation of
this compound, Huckel-Molecular Orbital calculations were
performed with an aim to highlight the sensitive nature of energy
contributions coming from the π-electron and the nonbonded
interactions in this class of molecules.12 These molecules provide
an excellent chemical model to understand the relationship
between molecular conformation and electronic/structural features
resulting from different substituents present on the molecular
framework. The conformational flexibility associated with C−C
and C−N bond rotation connected to the two phenyl rings allows
different conformers to be trapped/isolated. This leads to the
existence of conformational polymorphs. One such example is the
case of N-(p-methylbenzylidene)-p-methylaniline which exhibits
trimorphic behavior in the solid state (concomitant polymorphism
wherein crystals are obtained from ethanol),13 wherein both planar
and nonplanar conformations have been observed in different
forms. The energies associated with these conformations have
been estimated by ab initio calculations. The nonplanar con-
formation was found to be more stable by 6.57 kJ/mol over the
planar conformation.14 Thus the presence of disorder in the
crystalline environment seems to contribute to lattice energy of
certain magnitude to stabilize a high energy conformation.15
Although the Form II had a normal perfectly ordered average
structure, three-dimensional (3D) X-ray data collected on this
form indicates strong diffuse scattering reflecting the fact that
substantial thermal disorder is present.16Another case is provided
by p-chloro-N-(p-chlorobenzylidene)aniline which exists in the
planar triclinic form17a and nonplanar monoclinic form.17b Lattice
energy calculations established the planar form to be stable by
4.39 kJ/mol.17c,d The conformational flexibility (pedal motion)
associated with these compounds results in the existence of differ-
ent molecular conformations. This has been studied in stilbenes,18a
azobenzenes,18b and cyano substituted benzanilides.18c Variable
temperature X-ray diffraction data collected on single crystals allow
a detailed analysis of both static and dynamic disorder present in
the crystals.18d This approach has also been applied to investigate
conformational changes in nitro, methyl, methoxy, carboxylic, and
chloro substituted N-benzylideneanilines by Ogawa and co-
workers.18e The above-mentioned aspects relate well with our
Scheme 1. Chemical Scheme of All the Studied Compounds
Where X1 = -H/-F; X2 = -H/-F
a
a
The crystal structures of C.N. 14 and 15 could not be determined.
synthesized and characterized using Fourier transform infrared
spectroscopy (FTIR), Nuclear magnetic resonance (NMR),
differential scanning calorimetry (DSC), etc. Five of these were
found to be liquid at 25 °C. Three of these five liquids could be
crystallized using an in situ20 crystallization technique. The crystal
structures of 13 compounds have been thoroughly studied for the
identification of unique supramolecular motifs involving fluorine in
addition to other weak interactions which contribute toward the
stability of the crystal packing.
EXPERIMENTAL SECTION
■
Procedure for Synthesis. All the starting materials, namely, the
ortho, meta, and para fluorinated benzaldehydes and the corresponding
ortho, meta, and para fluorinated anilines, were purchased from Sigma
Aldrich and were used without further purification. Fluorobenzalde-
hyde (0.02 mol) was added to the solution of fluoroaniline (0.02 mol)
in about 25.0 mL of toluene. The reaction mixture was then refluxed
for 3 h in the presence of 4 Å activated molecular sieves. The com-
pletion of the reaction was monitored by thin layer chromatography
(TLC). After completion of the reaction, the mixture was filtered using
Whatman filter paper and the resulting solvent was then evaporated.
The crude product thus obtained was purified by a neutral column.
Procedure to Activate Molecular Sieves. The molecular sieves
were first washed with acetone and then kept in the oven at 120 °C for
1 day. These were further activated in the microwave oven for 1.0 min
before using them for the reaction.
Procedure of Neutral Column. The slurry of 100−200 mesh silica
was made in hexane, and then 10−15 mL of triethylamine was added to the
same. The column was packed using this slurry. Solution of the crude pro-
duct in the minimum amount of hexane was loaded into the column. The
column was then run by slowly increasing the polarity to 5% ethylacetate/
hexane. Distilled hexane and ethylacetate were used for this purpose.
Scheme 1 describes all the molecules studied and the method used
for their nomenclature. Out of 15 compounds synthesized, 10 were
solids at room temperature while the remaining five compounds
[compound numbers (C.N.) 5, 8, 11, 14, and 15] were liquids. One of
these (C.N. 9) was found to exhibit polymorphism.
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All the synthesized compounds were characterized by FTIR [Figure
S1a−o] and H NMR [Figure S2a−o] spectroscopy. Melting points
Crystallographic Modeling of Disorder. Among all 15 com-
pounds, compounds 1, 4, 5, 7, 9 (both polymorph I and polymorph II),
and 11 were found to be disordered. In the case of compounds 1, 5
(Z′ = 0.5), and both forms of 9, the molecules display positional
disorder around the CN bond which were refined with 0.5
occupancy using the PART command in SHELXL97 and the thermal
parameters were constrained to be equal by the EADP command in
SHELXL 97 [Figure S6a,e,i]. In the case of the compound 4 (Z′ = 2),
both molecules in the asymmetric unit were found to be disordered at
two orientations around the CN bond with the occupancy ratio of
0.941(2):0.059(2) for molecule A and 0.935(2):0.065(2) for molecule
B for 100 K data [Figure S6d].The corresponding values for 200 K
data are 0.946(3):0.054(3) and 0.936(3):0.064(3), and for 298 K data
are 0.960(3):0.040(3) and 0.951(3):0.049(3), respectively, indicating
the presence of static disorder in the crystal structure. The disorder
was analyzed using the PART command in SHELXL97 and refined
for two independent positions, namely, A and B (“A” for higher
occupancy). For the purpose of refinement, the carbon atom positions
for A and B in the benzene ring were fixed at the same position using
the EXYZ command in SHELXL97. Thermal parameters were also
constrained to be equal for the atoms at the same position using the
EADP command in SHELXL97. All hydrogen atoms were then
positioned geometrically and refined using a riding model with Uiso(H) =
1.2Ueq(C,N). In the case of the compound 7 (refined with Z′ = 0.5), the
true molecule (possessing fluorine substitution at para on aniline side
while ortho at benzaldehyde side) does not have any symmetry, and
the requirement of Z′ = 0.5 suggests the presence of crystallographic
disorder around the CN bond, which generates the second half of
the molecule around the center of inversion as is depicted in Figure S6g.
Careful refinements with equal occupancy at two independent
positions (namely, A and B for benzene ring) with similar refinement
strategy as mentioned previously for compound 4 were performed.
The fluorine atoms in the molecule are also found to be disordered at
two independent positions with the occupancy being 0.5 each. The
compound 11 (liquid at RT) in the crystal is found to be statistically
disordered and carefully refined at two independent orientations,
namely, “A” (for major one) and “B” (for minor one), using the PART
command in SHELXL97, the final population ratio being
0.850(6):0.150(6) [Figure S6k]. Except fluorine all other atoms in
the minor conformer were refined isotropically with thermal param-
eters of all carbon atoms being constrained to the same value using
EADP in SHELXL97. The benzene rings of minor conformer were
constrained to be a regular hexagon using FLAT command and C−C
bond lengths were restrained to 1.39 Å using DFIX in SHELXL97.
The C−C−C bond angles in the benzene ring were also restrained to
the same value using the SADI command in SHELXL97. The remain-
ing molecules 2, 3, 6, 8, 10, 12, and 13 do not exhibit any disorder in
the crystal structures.
1
(Table S1) were recorded and the DSC traces for all the solid
compounds are given in the Supporting Information [Figure S3a−j].
Powder X-ray diffraction (PXRD) data were recorded for the solid
compounds and compared with the simulated PXRD patterns
generated from the crystal coordinates in Mercury 3.0,21 and the
final plots were done in Origin 6.1 [Figure S4a−m]. It has been found
that the simulated PXRD patterns were matching with the PXRD
patterns recorded on the bulk samples, except for the two polymorphs
(polymorphs I and II) of C.N. 9. For compound 9, the experimental
profiles for the recorded PXRD pattern were refined with the lattice
parameters of both the forms using the program JANA2000.22 The
profile fitting parameters Rp and wRp were 8.77% and 12.89%
respectively [Figure S5].
Crystal Growth, Diffraction Data Collection and Structure
Solution. Single crystals of all the purified solids were grown from
different common organic solvents (methanol, ethanol, acetone,
chloroform, dichloromethane, hexane, toluene, acetonitrile, etc.) and
solvent mixtures (polar and nonpolar solvent combinations) (Table 1)
at low temperature (4 °C or −20 °C). All the crystallization products
were screened under an optical polarizing microscope for the identi-
fication of the crystal morphologies and were then checked by unit cell
determination using the single crystal X-ray diffraction (SCXRD)
technique for the identification of different polymorphs, if any. Only
compound 9 yielded two polymorphs from two different solvents
(hexane and methanol). SCXRD data for all the compounds were
collected using a Bruker AXS KAPPA APEX-II CCD diffractometer
(monochromatic Mo Kα radiation) equipped with an Oxford cryo-
system 700 Plus at 100.0(1) K. Data collection and unit cell refine-
ment for the data sets were done using the Bruker APEX-II23 suite,
data reduction and integration were performed by SAINT V7.685A12
(Bruker AXS, 2009), and the absorption corrections and scaling were
done using SADABS V2008/112 (Bruker AXS). The crystal structures
were solved by using Olex224 or WinGx25 packages using SHELXS97,26
and the structures were refined using SHELXL97.26 All the hydrogen
atoms have been geometrically fixed and refined using the riding
model. Table 1 lists the crystal and refinement data for 13 compounds.
All the packing and the interaction diagrams have been generated using
Mercury.21 Geometric calculations have been done using PARST27 and
PLATON.28
Crystal Growth and Data Collection for Liquids. Compounds
5, 8, 11, 14, and 15 are liquids at room temperature and were
subjected to in situ crystallization. In all the cases, the compound was
taken in an 0.3 mm Lindemann quartz capillary and was sealed at both
ends with glue and was mounted on Bruker AXS KAPPA APEX-II
CCD diffractometer with the capillary aligned vertically. For com-
pound 5, the capillary was then cooled at 360 K/h to 200 K but the
liquid did not solidify by itself. A zone of the capillary was heated by
the CO2 LASER of the OHCD29 and suddenly the heat was with-
drawn. This was repeated a few times to initiate crystallization in the
capillary. Then the capillary was warmed up to 220 K and a few cycles
of zone melting scans using the CO2 LASER of the OHCD were
repeated for 3 h to grow a single crystal in the capillary. After the
formation of a single crystal, one Φ scan (scan width 0.3°, 1200 frames)
data were collected keeping ω and κ fixed at 0° and the detector fixed at
30° and with a detector distance of 6.0 cm.
Theoretical Calculations. The intermolecular interactions
observed in these compounds are of the type C−H···F and C−H···π
[Table 2]. The sum of the van der Waals radii30 has been considered
as the limiting distance for the evaluation of different interactions
present in these compounds. The primary supramolecular motifs
which include chains and dimers formed by C−H···F interactions have
been used as inputs for the program FIREFLY31 to calculate inter-
action energies and the corresponding CIFs were used as input for
PIXEL calculations.32
For compound 8, the capillary was cooled to 250 K. The liquid
solidified to a polycrystalline mass on cooling. Several zone melting
scans using the CO2 LASER were done for about 12−13 h to get
single crystals of the compound in the capillary. Similar Φ scan data
were collected, the scan width being 0.5° (720 frames).
Compound 11, was cooled from 290 to 140 K first at 360 K/h,
which resulted in the formation of a glassy material. Then it was
warmed to 240 at 200 K/h. Zone melting scans using the CO2 LASER
from bottom to top always resulted in a glassy material. Thereafter,
zone melting scans were done from top to bottom for 3 h. This scan
resulted in the crystallization of the material, though the crystals were
not of very good quality. Similar Φ scan data were collected with a
scan width 0.3° (1200 frames).
The interaction energy (IE) calculations were performed using
FIREFLY, previously known as the PC GAMESS, at the density
functional theory (DFT) level using B3LYP function and 6-31G as the
basis set. GABEDIT33 was used as a graphical interface for FIREFLY.
The primary coordinates for the molecules under study were taken
from their respective experimentally determined crystal structures (at
100 K). Table 2a lists all these intermolecular interactions along with
their interaction energies. The energies of the different monomers
(Emonomer) or dimers (Edimer) were calculated at the same level of
theory. The stabilization energy of the dimer (ΔEdimer) was calculated
using the formula ΔEdimer = [Edimer − (2 × Emonomer)]. If the dimer is
formed by two identical C−H···F−C interactions, then the
corresponding interaction energy is reported as ΔEdimer/2. If the
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Table 1. Crystallographic Data for Compounds 1−13
data
1
2
3
4
5
6
7
formula
FW
C13H9F2N
217.21
884979
EtOH
C13H9F2N
217.21
C13H9F2N
217.21
884985
MeOH
needle
C13H9F2N
217.21
884986
DCM
C13H9F2N
217.21
884987
in situ
C13H9F2N
217.21
884988
ACN
C13H9F2N
217.21
884989
MeOH
block
CCDC no.
solvent system
morphology
crystal system
space group
a (Å)
884984
DCM + hexane
block
plate
plate
in situ
block
triclinic
monoclinic
P21/c
monoclinic
P21
triclinic
monoclinic
P21/c
orthorhombic
P212121
6.4645(2)
12.0553(4)
13.1914(4)
90
monoclinic
P21/c
P1
̅
P1
̅
5.728(5)
7.416(5)
12.487(5)
105.745(5)
98.559(5)
90.003(5)
504.4(6)
2
14.530(3)
5.747(1)
12.345(3)
90
6.0664(3)
14.1400(5)
12.0036(5)
90
7.252(5)
11.594(5)
13.535(5)
64.666(5)
75.500(5)
89.803(5)
988.8(9)
4
7.212(2)
5.862(1)
12.443(3)
90
7.202(2)
5.900(1)
12.292(2)
90
b (Å)
c (Å)
α (°)
β (°)
γ (°)
volume (Å3)
107.326(1)
90
90.228(2)
90
108.521(2)
90
90
108.789(6)
90
90
984.1(4)
4
1029.65(8)
4
498.9(2)
2
1028.03(6)
4
494.4(1)
2
Z
ρ (g/cm3)
1.43
1.466
1.401
1.459
1.446
1.403
1.459
μ (mm−1
F(000)
θmin,max
)
0.110
0.113
0.108
0.112
0.111
0.108
0.112
224
448
448
448
224
448
224
1.72, 25.03
2.94, 25.02
1.70, 25.03
1.73, 25.03
2.98, 24.98
2.29, 24.99
2.99, 25.02
h
min,max; kmin,max; lmin,max −6, 5; −8, 8;
−16, 17; −3, 6;
−3, 7; −16, 16;
−8, 8; −13, 13;
−8, 8; −3, 3;
−6, 7; −14, 14;-
−8, 8; −5, 7;
−14, 14;
−14, 14
−14, 13
−16, 15
−14, 14
15, 15
−14, 13
no. of reflections.
7796
5454
5976
11528
2208
19712
3719
no. unique/observed
reflections.
1761/1513
1734/1639
3448/3327
3474/3181
606/579
1815/1766
864/752
no. of parameters
wR2_obs, R_obs
145
145
290
303
74
145
79
0.117, 0.045
−0.277, 0.429
1.126
0.0996, 0.0331
−0.198, 0.259
1.039
0.0655, 0.026
−0.134, 0.124
1.078
0.1618, 0.0582
−0.443, 0.787
1.092
0.0752, 0.0273
−0.193, 0.104
1.082
0.1117, 0.0367
−0.181, 0.410
1.132
0.1466, 0.0454
−0.305, 0.356
1.172
Δρmin,max(e Å−3
GOF
)
data
8
9F1
9F2
10
11
12
13
formula
FW
C13H9F2N
217.21
884990
in situ
C13H9F2N
217.21
884991
hexane
plate
C13H9F2N
217.21
884992
MeOH
plate
C13H10FN
199.22
884980
EtOH
C13H10FN
199.22
884981
in situ
C13H10FN
199.22
C13H10FN
199.22
CCDC no.
solvent system
morphology
crystal system
space group
a (Å)
884982
DCM + hexane
thin rod
orthorhombic
P212121
6.3184(3)
12.0035(6)
13.3787(7)
90
884983
DCM + hexane
block
in situ
plate
in situ
monoclinic
P21/c
monoclinic
P21/c
orthorhombic
P212121
3.8396(6)
11.871(2)
22.205(4)
90
monoclinic
P21/n
monoclinic
P21/c
triclinic
P1
̅
15.393(9)
3.851(2)
22.616(2)
90
9.8109(9)
3.7789(3)
27.044(3)
90
5.6613(1)
25.0212(5)
7.1416(1)
90
12.022(2)
7.913(2)
12.242(4)
90
5.594(1)
7.225(1)
12.569(2)
91.99(1)
97.70(1)
90.29(1)
503.1(2)
2
b (Å)
c (Å)
α (°)
β (°)
γ (°)
volume (Å3)
132.377(7)
90
90.991(5)
90
90
90.216(1)
90
119.589(2)
90
90
90
90
990.3(10)
4
1002.5(2)
4
1012.2(3)
4
1011.62(3)
4
1012.8(4)
4
1014.68(9)
4
Z
ρ (g/cm3)
1.457
1.439
1.425
1.308
1.307
1.304
1.315
μ (mm−1
F (000)
θmin,max
)
0.112
0.111
0.110
0.090
0.090
0.089
0.090
448
448
448
416
416
416
208
2.44, 25.02
1.51, 25.01
1.95, 27.48
1.63, 23.53
3.21, 25.02
2.28, 25.02
2.82, 26.35
h
min,max; kmin,max; lmin,max −18, 18; −2, 2;
−11, 11; −4, 4;
−4, 4; −10, 15;
−6, 6; −27, 27; −14, 14; −6, 6;
−7, 7; −13, 14;
−6, 6; −9, 9;
−26, 26
−32, 31
−23, 28
−8, 7 −14, 14
−15, 7
−15, 15
no. of reflections.
4157
8802
8465
6169 4446
2946
6030
no. unique/observed
reflections.
1266/1062
1781/1555
2299/2144
1494/1356
1395/1290
1724/1612
2034/1635
no. of parameters
145
145
145
136
185
136
136
wR2_obs, R_obs
0.2054, 0.076
−0.584, 0.360
1.109
0.093, 0.0342
−0.193, 0.390
1.102
0.0916, 0.0335
−0.278, 0.226
1.125
0.0796, 0.0315
−0.181, 0.305
1.048
0.2592, 0.1032
−0.349, 0.760
1.168
0.0940, 0.0368
−0.17, 0.327
1.061
0.1051, 0.0414
−0.202, 0.450
1.046
Δρmin,max(e Å−3
)
GOF
dimer is formed by two different C−H···F−C interactions, then the
combined interaction energy is reported. If only one such interaction is
present between the two interacting molecules then the interaction
energy is taken as ΔEdimer. Lattice energies of these molecules were
calculated using the CLP package. The results from the CLP package
indicated contributions of Coulombic, dispersion, polarization, and
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Crystal Growth & Design
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a
Table 2. (a) Intermolecular C−H···F and C−H···N Interactions in All the Crystallized Compounds and (b) Intermolecular
b
C−H···π and C−F···π Interactions
(a) Intermolecular C−H···F and C−H···N Interactions
CN
C−H···F
symmetry code
x, y + 1, z + 1
C···F (Å)
H···F (Å)
∠C−H···F(deg)
IE (kcal/mol)
1
C5−H5···F1
C11−H11···F2
C5−H5···F2
C12−H12···F1
C10−H10···F1
C13−H13···F1
C9−H9···F2
3.361(2)
3.372(2)
3.219(1)
3.469(1)
3.326(2)
3.214(7)
3.357(8)
3.242(7)
3.354(4)
3.318(3)
3.274(4)
3.366(1)
3.494(3)
3.513(4)
3.322(1)
3.483(2)
3.392(3)
3.277(3)
3.15(3)
2.57
2.58
2.48
2.44
2.56
2.18
2.58
2.20
2.47
2.47
2.45
2.62
2.47
2.50
2.49
2.48
2.35
2.44
2.22
2.44
2.41
2.53
2.59
2.54
2.51
2.58
2.61
2.37
2.32
2.61
2.61
2.56
2.67
130
129
125
159
137
160
128
161
138
134
133
125
159
155
133
154
162
133
144
125
168
156
129
130
176
120
126
161
168
145
120
122
135
−2.46
−2.33
−1.40
−1.73
−1.53
−4.93
−0.95
−4.74
−1.70
−1.61
−1.57
−2.00
−2.25
−1.85
−1.62
−2.59
−4.92
−0.50
−1.00
−1.79
−5.65
x − 1, y − 1, z − 1
−x + 1, −y, −z + 1
x, −y − 1/2, z − 1/2
−x, 1 − y, −z
2
3
4
c
x + 1, y, z
x, y, z − 1
x − 1, y, z
−x, −y + 1, −z − 1
−x + 1, −y, −z + 2
−x, −y, −z + 1
C26−H26···F3
C22A−H22A···F3A
C4A−H4A···F2A
C17A−H17A···F4A
C4A−H4A···F1A
C12A−H12A···F4A
C15A−H15A···F2A
C4−H4···F1
x, +y, +z + 1
c
c
−x, −y, −z + 1
x, y, z − 1
−x + 2, −y, −z + 1
x, −y − 1/2, + z − 1/2
x − 1, y, z
−x + 2, −y, −z + 1
−x + 1, −y + 1, −z
x, −y + 1/2, z + 1/2
−x + 1, y − 1/2, −z + 1/2
−x + 1, y − 1/2, −z + 1/2
−x, −y + 1, −z + 1
−x + 1, y + 1/2, −z + 1/2
x − 1/2, −y + 1/2, −z
−x − 1/2, y + 1/2, −z + 1/2
−x + 3/2, y + 1/2, −z + 1/2
x, −y + 1/2, z + 1/2
x − 1, y, z
5
c
C6−H6···F1
6
7
C13−H13···F1
C5A−H5A···F2
C7−H7···F1
c
C5A−H5A···F1
3.241(4)
3.470(7)
3.546(6)
3.377(2)
3.335(2)
3.588(2)
3.255(2)
3.354(2)
3.41(1)
8
C8−H8···F1
C13−H13···F1
C5−H5···F1
C4−H4···F1
C11−H11···F1
C3−H3···F1
C5−H5···F1
C8A−H8A···F1A
C13−H13···F1
C8−H8···N1
C9−H9···F1
C11−H11···F1
C6−H6···N1
9F1
9F2
−3.48
−4.39
−2.34
−1.38
−1.64
−3.25
−3.87
−0.42
−1.27
−1.33
−1.29
10
11
12
3.387(2)
3.552(2)
3.290(2)
3.272(2)
3.510(2)
x − 1/2, −y + 3/2, −z + 2
x, y, 1 + z
13
−1 + x, y, 1 + z
−x + 2, −y + 1, −z
(b) Intermolecular C−H···π and C−F···π Interactions
symmetry code
1 − x, 2 − y, −z
2 − x, 1 − y, −z
1 − x, 1 − y, −z
2 − x, 2 − y, −z
1 − x, 1/2 + y, 3/2 − z
x, 1/2 −y, 1/2 + z
x, 3/2 − y, −1/2 + z
−x, −1/2 + y, 1/2 − z
x, y, z
CN
C−H/F···π
C2−H2···Cg2
C5−H5···Cg2
C8−H8···Cg1
C11−H11···Cg1
C3−H3···Cg1
C···π (Å)
3.506 (2)
3.526(2)
3.461(2)
3.544 (2)
3.460(1)
3.448(1)
3.469(1)
3.441(1)
3.448(6)
3.444(7)
3.414(6)
3.642(7)
4.006(6)
3.478(4)
3.460(4)
3.522(4)
3.491(4)
3.463(4)
3.465(4)
3.436(4)
3.439(4)
3.512(2)
3.443(2)
H/F···π (Å)
∠C−H/F···π (deg)
1
2
3
2.86
2.82
2.77
2.85
2.80
2.81
2.74
2.73
2.80
2.66
2.63
2.87
3.117(5)
2.80
2.80
2.84
2.85
2.78
2.75
2.75
2.72
2.84
2.75
126
131
130
130
129
125
134
133
126
140
140
139
122(1)
129
127
130
126
130
132
130
133
129
130
C6−H6···Cg2
C8−H8···Cg1
C11−H11···Cg2
C16−H16···Cg2
C8−H8···Cg4
C21−H21···Cg2
C11−H11···Cg3
C25−F3···Cg1
C3A−H3A···Cg4
C16A−H16A···Cg1
C6A−H6A···Cg3
C19A−H19A···Cg2
C8A−H8A···Cg4
C21A−H21A···Cg1
C11A−H11A···Cg3
C24A−H24A···Cg2
C2−H2···Cg1
−x, y + 1/2 −z + 1
−x + 1, y −1/2, −z + 1
x + 1, y, z
x −1, y, z + 1
x + 1, y, z + 1
4
−x + 1, −y, −z + 1
−x, −y, −z + 1
x −1, y, z
−x + 1, −y + 1, −z
x, y, z − 1
x, y, z
−x, 1 − y, −z
1 − x, 1/2 + y, 1/2 −z
−x, −1/2 + y, 1/2 − z
5
C5−H5···Cg1
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Table 2. continued
(b) Intermolecular C−H···π and C−F···π Interactions
6
C4−H4···Cg2
C10−H10···C13
C3A−H3A···Cg1
C6A−H6A···Cg1
C2−H2···Cg2
1 − x, 1/2 + y, 1/2 − z
3/2 − x, −y, 1/2 + z
1/2 + x, 1 − y, −1/2 + z
−1/2 + x, −y, −1/2 + z
1/2 + x, 1/2 − y, −1/2 + z
1/2 + x, 1/2 −y, 1/2 + z
−1/2 + x, 1/2 −y, −1/2 + z
1 − x, −y, −z
2 − x, −1/2 + y, 1/2 − z
3/2 − x, 1 −y, 1/2 + z
1 − x, −y, −z
2 − x, 1 − y, −z
1 − x, 1 − y, −z
3.625(6)
3.736(1)
3.535(4)
3.451(3)
3.407(2)
3.552(2)
3.514(2)
3.605(9)
3.617(2)
3.717(1)
3.506(2)
3.538(2)
3.478(2)
3.610(2)
2.78
2.89
2.86
2.78
2.72
2.84
2.84
2.86
2.78
2.86
2.82
2.83
2.71
2.92
149
149
131
130
131
134
130
136
148
150
129
132
136
128
d
7
10
C9−H9···Cg1
C11−H11···Cg1
C5A−H5A···Cg2
C4−H4···Cg2
C10−H10···C13
C3−H3···Cg2
C5−H5···Cg2
C8−H8···Cg1
C12−H12···Cg1
11
12
d
13
2 − x, −y, −z
a
The values in italics indicate “neutron-corrected” distances. The C−H bond distances for X-ray and neutron data are 0.95 Å and 1.08 Å,
b
respectively. Cg1, Cg2, Cg3, and Cg4 refer to the center of gravity of the ring formed by C1−C6, C7−C12, C14−C19, and C20−C25 respectively.
c
d
These have contributions both from C−H···π and C−H···F interactions. Refers to the imine double bond.
repulsive components to the total lattice energy [Table S2]. DFT
calculations using B3LYP/6-31G basis set were performed using
FIREFLY with crystallographic coordinates as a starting set (only the
major conformers were introduced in the calculations in the case of
disordered molecules) to obtain the optimized geometry of an isolated
molecule. Selected torsion angles obtained from theoretical calcu-
lations were compared with the experimentally obtained values (Table 3).
indicate weak but significant contribution toward stabilization
of crystal structure by these interactions.
3. 2-Fluoro-N-(4-fluorobenzylidene)aniline. Compound
3 crystallizes in the monoclinic noncentrosymmetric P21 space
group with two molecules (A and B) in the asymmetric unit
connected via a weak C−H···π hydrogen bond [Figure S6c]
(Table 2b). Both the molecules (A and B) present in the
asymmetric unit are found to form molecular chains through
short, highly directional, and significantly stabilizing C−H···F
interactions involving the highly acidic imine hydrogen H13
with F1 [2.18 Å, 160°, −4.93 kcal/mol] and H26 with F3 [2.20 Å,
161°, −4.74 kcal/mol] respectively [Figure 3a, Table 2a]. The
molecular chains are interlinked by the utilization of weak
C−H···π (involving H8, H11and H21) and C−F···π (involving
F3 with Cg1) interactions, and thus alternating ...ABAB... layers
along the crystallographic b-axis are generated [Figure 3b].
4. 4-Fluoro-N-(3-fluorobenzylidene)aniline. Compound
RESULTS
■
Figures S6a−m show the ORTEP for all the compounds. All the
dihedral angles between the least-squares planes containing the
aniline and benzaldehyde moiety are contained in Table S3.
It is of interest to note that the presence of electron with-
drawing fluorine atoms is responsible for increasing the acidity
of the neighboring hydrogen atoms in the phenyl ring, in
addition to the imine hydrogen which is highly acidic and parti-
cipates in the interactions as well (Table 2). In the absence of
strong hydrogen bond donors, the salient features associated
with the crystal packing of all the compounds in the current
study essentially consist of C−H···F and C−H···π intermolecular
interactions.
4 crystallizes in the triclinic centrosymmetric P1 space group
̅
with two molecules (A and B) in the asymmetric unit con-
nected via a weak C−H···π interaction [Figure S6d]. Both
molecules in the asymmetric unit were found to be disordered
at two orientations around the CN bond, and this was modeled
carefully as described earlier in the Experimental Section, the ratio
of the major and minor conformer being 0.941(2):0.059(2) for
molecule A and 0.935(2):0.065(2) for molecule B for 100 K data.
The population of the two conformers remained invariant when
the crystal data were collected at 200 K and 298 K respectively,
indicating the presence of static disorder. The atoms in the major
conformer of both the molecules were considered for inter-
molecular interactions analysis (Table 2). The packing of molecule
A parallel to the bc plane displays the formation of a layer motif
with the utilization of weak C−H···F interactions (involving acidic
hydrogens H4A with F2A and H4A with F1A forming dimeric
motifs) [Figure 4a]. Another dimeric pair of C−H···F interactions,
involving acidic hydrogens H22A with F3A and H17A with F4A
pack the molecules B to generate layers parallel to the bc plane
[Figure 4a]. These two layers of molecules A and B are inter-
connected by weak C−H···π and C−H···F (involving H12A with
F4A and H15A with F2A) intermolecular interactions [Figure 4a,b]
(Table 2) in the crystal lattice. The interaction energies evaluated
for all C−H···F interactions present in the crystal packing range
between 1.50 and 2.5 kcal/mol.
1. 4-Fluoro-N-(4-fluorobenzylidene)aniline. Compound
1 crystallizes in the centrosymmetric triclinic P1 space group
̅
with Z = 2 [Figure S6a]. The central CN bond exhibits
positional disorder, the two independent conformations being
present in a 1:1 ratio. The C−H···F interactions, involving H5
with F1 (IE = −2.46 kcal/mol) and H11 with F2 (IE = −2.33
kcal/mol) respectively, pack the molecules to generate molecular
sheets [Figure 1a, Table 2a]. These sheets are further inter-
connected via weak C−H···π intermolecular interactions forming
dimers in the solid state [Figure 1b] (Table 2b).
2. 3-Fluoro-N-(4-fluorobenzylidene)aniline. Compound
2 was found to crystallize in the monoclinic centrosymmetric
P21/c space group [Figure S6b]. Molecules related to each
other by the inversion center were found to form molecular
layers by head to head and tail to tail dimers, involving acidic
hydrogens H10 and H5 with F1 and F2 respectively [Figure 2,
Table 2a]. The molecular layers were again found to interact
through weak C−H···F interactions, involving H12 and F1,
propagating along the c-glide along with C−H···π interactions
(involving H3, H6, H8, and H11) (Table 2). The interac-
tions energies associated with these C−H···F interactions were
found to lie between −1.4 to −1.8 kcal/mol (Table 2a), which
5101
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Crystal Growth & Design
Article
a
and C−H···π interactions, involving H2 and H5 of the aromatic
ring [Figure 5] (Table 2).
Table 3. Selected Torsion Angles (°)
6. 2-Fluoro-N-(3-fluorobenzylidene)aniline. Compound
6 was found to crystallize in the orthorhombic noncentrosym-
metric P212121 space group with Z = 4 [Figure S6f]. A short
and highly directional C−H···F interaction, involving the
sufficiently acidic imine hydrogen H13 and F1 [2.35 Å, 162°]
forms a molecular ladder along the crystallographic a axis
[Figure 6a, Table 2b]. The interaction energy associated with
the C−H···F hydrogen bond is found to be one of the most
stabilizing (−4.92 kcal/mol), among all 13 crystal structures.
The weak C−H···π (involving H4 and H10 with imine carbon
utilizes the 21 screw parallel to b-axis) intermolecular inter-
actions linked such chains [Figure 6a, Table 2b]. The packing
of the molecules was found to display the herringbone pattern
when viewed down the crystallographic bc plane in the crystal
structure [Figure 6b].
7. 4-Fluoro-N-(2-fluorobenzylidene)aniline. Compound
7 crystallizes in the monoclinic space group P21/c with Z = 2
(Z′ = 0.5) [Figure S6g]. The disorder associated with this mol-
ecule was carefully refined (as is mentioned in the Experimental
Section). The crystal packing of the molecules involves the genera-
tion of a molecular sheet down the bc plane [Figure 7a] (Table 2a)
via dimeric C−H···F intermolecular interactions, involving acidic
hydrogens H5A with F2 (−0.50 kcal/mol) and H7 with F1 (−1.00
kcal/mol). Furthermore, the C−H···π interactions, involving H6A
and H3A, along with C−H···F intermolecular interactions,
involving H5A and F1 (−1.79 kcal/mol), provide additional
stability to the crystal packing in between the sheet-like structure
[Figure 7b] (Table 2b).
8. 3-Fluoro-N-(2-fluorobenzylidene)aniline. Compound
8 was indexed to a monoclinic space group P21/c with Z = 4
[Figure S6h]. The molecules were found to form heterodimers
by C−H···F interactions, involving H8 and H13 with F1 (the
total interaction energy is −5.65 kcal/mol) [Figure 8a, Table 2a],
which extend over the crystal lattice [Figure 8b]. The molecular
dimer is further connected with another dimer, propagating
along the crystallographic b-axis via C−H···F (again involving
H8 and H13 with F1) interactions and thus generating a chain of
heterodimers along that axis.
9A. 2-Fluoro-N-(2-fluorobenzylidene)aniline (Poly-
morph I). Compound 9 was found to have two polymorphs
I and II, but with similar plate-like morphology. Poly-
morph I was crystallized from the nonpolar solvent hexane,
while polymorph II was crystallized from the polar solvent
methanol (MeOH). In both polymorphs, the conforma-
tional disorder exists around the CN bond, the ratio of
both conformers being 1:1. Polymorph I was solved in
monoclinic P21/c space group with Z = 4 [Figure S6(i)-1].
Discrete molecular dimers have been found to form by
weak C−H···F intermolecular interactions (involving H5
with F1, −3.48 kcal/mol) in the crystal packing, and no
other significant interactions were observed between these
dimers forming molecular sheets in the solid [Figure 9a]
(Table 2a).
C8−C7−N1−C13
C21−C20−N2−
C6−C1−C13−
N1 C19−C14−
C1−C13−N1−
C7 C14−C26−
b
b
b
torsion angle
C26
C26−N2
N2−C20
N-benzylideneaniline 56.83(2)
9.92(2)
179.51(2)
176.92
34.94
0.88
c
c
compound 1
44 (2), 36.7(16)
6.7(19), 18(2)
177.1(11),
180.0(13)
c
35.59
1.70
178.31
compound 2
compound 3
14.73(16)
34.08
11.76(16)
1.09
178.87(8)
176.88
b
b
42.6(8), 44.9(8)
10.7(9), 9.0(9)
175.6(5),
177.2(5)
b
41.78, 42.72
8.44, 7.62
173.97, 175.55
b
b
compound 4
4.7(4), 14.7(4)
4.6(4), 12.8(4)
179.6(2),
178.1(2)
b
27.20, 36.16
1.97, 2.47
176.75, 176.97
compound 5 (half
molecule)
8.22(5)
10.26(7)
178.92(6)
33.09
35.0(3)
38.43
12(3)
31.1
0.59
177.07
compound 6
compound 7
compound 8
0.6(3)
0.02
178.25(16)
176.12
19(3)
0.70
172(2)
177.07
39.7(8)
32.27
5.8(9)
0.64
174.1(5)
177.14
c
compound 9 form I 42.2(12),
5.5(13), 4.8(14) 175.6(2),
c
c
c
43.3(12) , 36.98
, 0.75,
177.5(3)
176.23,
,
c
c
compound 9 form II 20.3(7), 25.3(4)
2.0(5), 29.0(8) , 163.0(8),
37.41
0.45
168.6(8) ,
176.09
compound 10
compound 11
compound 12
compound 13
46.5 (2)
33.28
7.7(2)
0.82
178.8(1)
176.95
50.4(10)
36.77
8.2(11)
1.08
175.6(8)
176.68
33.5(3)
39.18
2.6(3)
0.28
178.64(15)
176.03
38.8(2)
34.48
17.7(2)
1.12
179.26(12)
176.88
a
Only major conformers were considered for disordered molecules.
Values in italics are obtained from theoretical B3LYP/6-31G
b
calculations. Equivalent torsion angle for the second molecule in
c
the asymmetric unit. Another torsion angle due to the presence of
disorder around the CN bond.
5. 3-Fluoro-N-(3-fluorobenzylidene)aniline. The com-
pound was found to crystallize in the monoclinic centrosym-
metric space group P21/c with Z = 2 (Z′ = 0.5). The Z′ = 0.5 in
the true molecule (possessing fluorine substitution at meta posi-
tion on both sides of the ring) having no symmetry suggests the
presence of static disorder around the imine bond (CN)
which generates the second half of the molecule around the
center of inversion [Figure S6e]. In the crystal lattice, the
molecules are found to pack through linear chains involving
dimeric C−H···F intermolecular interactions, namely, H4 with
F1 (−1.62 kcal/mol) [Figure 5] (Table 2a), which connect
with the other chains in the lattice by another independent set
of C−H···F interactions, involving H6 with F1 (−2.59 kcal/mol)
9B. 2-Fluoro-N-(2-fluorobenzylidene)aniline (Poly-
morph II). The polymorph II of 9 was found to crystallize in
the orthorhombic noncentrosymmetric P212121 space group
with Z = 4 [Figure S6(i)-2]. The molecules in the crystal pack
via the formation of zigzag chains, utilizing weak C−H···F inter-
molecular interactions, involving H4 with F1 (utilize 21 screw,
−4.39 kcal/mol) along the crystallographic b-axis [Figure 9b,
Table 2a]. Another C−H···F intermolecular interaction
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Figure 1. (a) Formation of sheets viewed down the ac plane by C−H···F interactions in 1. Disordered atoms were omitted for clarity. (b) Formation
of a molecular layer via weak C−H···π interactions in 1.
Figure 2. Formation of molecular layers by C−H···F and C−H···π intermolecular interactions in 2.
Figure 3. (a) Packing view displaying formation of molecular chains of both molecules of the asymmetric unit along the crystallographic a-axis which
are connected through C−H···π interactions in 3. (b) Formation of alternate .....ABAB..... layers via the network of weak C−H···π, C−H···F, and
C−F···π interactions in 3.
involving H11 with F1 (−2.34 kcal/mol) with the utilization of
21 connects the above-mentioned chain down the crystallo-
graphic a-axis [Figure 9b, Table 2a]. It is of interest to note that
there are no C−H···π intermolecular interactions present in
both the crystal forms of 9.
10. N-Benzylidene-4-fluoroaniline. This compound
crystallizes in the monoclinic centrosymmetric P21/n space
group [Figure S6j]. Packing in the crystal involves the forma-
tion of molecular sheet motif with the utilization of bifurcated
weak C−H···F intermolecular interactions, involving H3 and
H5 with F1 (−1.38 kcal/mol and −1.64 kcal/mol respectively)
propagating along the 21 screw down the crystallographic b-axis
[Figure 10a, Table 2]. Weak C−H···π (involving H2 with Cg2,
H9 and H11 with Cg1) intermolecular interactions stabilize the
layer motif, with the utilization of the n glide plane of symmetry
[Figure 10b, Table 2b)].
11. N-Benzylidene-3-fluoroaniline. Compound 11 crys-
tallizes in the monoclinic centrosymmetric P21/c space group
with Z = 4 [Figure S6k]. It is of interest to note that in situ
crystallization of the low-melting liquid results in trapping of
both the major and minor conformer of this molecule. It is to
be noted that a 180° rotation of the entire molecule around the
shorter axis results in the occurrence of the observed conforma-
tions. This kind of a molecular rotational process is very rare as
it involves steric interactions with the neighboring molecules in
the crystalline lattice.18d This feature of molecular disorder has
also been observed in N-benzylideneaniline and N-(4-methoxy-
benzylidene)-4-methylaniline.18d
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Figure 4. (a) Formation of layered motifs by both molecules (shown with different colors: gray and orange) of asymmetric unit via weak C−H···F
and C−H···π interactions in 4. The disordered hydrogen and carbon atoms having a lower occupancy have been omitted for clarity. (b) Packing
viewed down the ac crystallographic plane, displaying the formation of alternate layers of molecular sheets of A (gray) and B (orange) via C−H···F
and C−H···π interactions in 4.
Figure 5. Packing of the molecules of 5 viewed down the ac plane displaying formation of layers through C−H···F and C−H···π intermolecular
interactions.
Figure 6. (a) Formation of a molecular ladder down the ac plane by C−H···F intermolecular interactions in 6. (b) Packing viewed down the bc
plane, showing the formation of herringbone motifs by the utilization of C−H···π interactions in 6.
In 11, the packing of molecules involves the formation of
molecular chains, via weak C−H···F interactions (involving
H8A with F1A, −3.25 kcal/mol) with the utilization of c-glide
plane [Figure 11, Table 2a]. The chains are further linked with
dimeric C−H···π intermolecular interactions (involving H5A)
[Figure 11, Table 2b].
12. N-Benzylidene-2-fluoroaniline. Compound 12 crys-
tallizes in the orthorhombic non-centrosymmetric P212121
space group with Z = 4 [Figure S6(l)]. A short and highly direc-
tional C−H···F interaction (2.32 Å, 168°, −3.87 kcal/mol),
involving the highly acidic hydrogen H13 with F1, steers the
packing of molecules along the crystallographic a-axis [Figure
12a, Table 2a]. In addition, weak C−H···π (involving H4 with
Cg2) interaction forms molecular chains along the crystallo-
graphic b-axis generating a sheet-like structure. The packing of
the molecules in 12 also displays the formation of the herring-
bone pattern, with the utilization of weak C−H···N (involving
H8 with N1) and C−H···π (involving H4 and H10) inter-
molecular interactions [Figure 12b, Table 2].
13. N-(4-Fluorobenzylidene)aniline. Compound 13
crystallizes in the triclinic centrosymmetric space group P1
with Z = 2 [Figure S6m]. The packing of the molecules in the
crystal involves the formation of molecular sheets down the ac
plane with the utilization of bifurcated weak C−H···F inter-
molecular interactions, involving H11 and H9 with F1 (−1.27
kcal/mol and −1.33 kcal/mol respectively) [Figure 13a]. Further,
these sheets are stabilized by dimeric C−H···N (involving H6 with
N1, −1.29 kcal/mol) and C−H···π intermolecular interactions,
involving acidic H3 and H5 with electron rich phenyl ring Cg2
and H8 with Cg1 [Figure 13b] (Table 2).
̅
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Figure 7. (a) Packing of 7 down the bc plane showing the formation of the molecular sheet via weak C−H···F intermolecular interactions. (b) The
weak C−H···π and C−H···F intermolecular interactions viewed down the ac plane in 7.
Figure 8. (a) Formation of molecular heterodimeric motif by weak C−H···F intermolecular interactions in 8. (b) Packing view down the ac plane
shows extension of dimers in 8.
14. N-(3-Fluorobenzylidene)aniline. This compound was
found to be a liquid at 25 °C. Attempts to grow a single crystal
using in situ crystallization technique failed. The compound
formed a glass on cooling and did not show any signature of
crystallization on several cooling and heating cycles using the
Oxford cryosystem. This was followed by repeated attempts to
allow for sudden heating by OHCD and sudden cooling by
switching off the CO2 LASER. Hence, the structure for this
compound could not be determined.
15. N-(2-Fluorobenzylidene)aniline. This compound was
also found to be liquid at 25 °C. Several attempts to crystallize
the compound by cooling it to 200−150 K failed. OHCD was
also used to trigger crystallization by sudden thermal shock to
the liquid at 200 K. But all our efforts failed to crystallize
15. Hence, the structure for this compound could not be
determined.
the weak C−H···F interactions for different supramolecular
motifs have been evaluated. These are given in Table 2a, which
have interaction energies ranging from 1 to 5 kcal/mol and are
stabilizing in nature. It has also been established from electron
density studies,34 crystallographic database, and computational
evidence35 that C−H···F interactions have weak hydrogen
bond character. It is also of significance to note that C−H···F
hydrogen bonds with a H···F distance between 2.2 and 2.67 Å
and the angle ∠C−H···F ranging between 130 and 168° have
higher interaction energies (3 kcal/mol or more). Presumably
these weak C−H···F hydrogen bonds thereby influence the
preorganization of the molecules in the formation of molecular
layers, and such layer of molecules are held with the adjacent
layers by the involvement of weak C−H···π interactions and
additional independent C−H···F hydrogen bonds. C−H···π
interactions have recently received major recognition in all
fields of chemistry and biology. It has been debated whether it
has a hydrogen bond character or is essentially dispersive in
nature. The latest developments in the supramolecular chem-
istry of C−H···π are summarized in authoritative articles by
Nishio and co-workers.36 The results of PIXEL calculations are
shown in the Table S2. It is observed that the lattice energies of
these compounds are between 22 and 27 kcal/mol, although
these compounds have a range of different crystal structures,
which display a variety of supramolecular synthons.
DISCUSSION
■
The detailed analysis of these 13 crystal structures in the series
of fluorine substituted N-benzylideneanilines allows for a better
understanding of the role of weak intermolecular interactions
which stabilize the crystal packing in the absence of any strong
hydrogen bonds. The crystal packing in these compounds are
found to be mainly governed by the presence of short, highly
directional (in some cases >165°) C−H···F and C−H···π
interactions [Table 2]. The interaction energies associated with
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Figure 9. (a) The packing of the polymorph I of 9 viewed down the ac plane displays the generation of molecular sheet of dimers formed via
C−H···F intermolecular interactions. (b) The packing of polymorph II of 9 viewed down the bc plane, showing the formation of a molecular sheet
via C−H···F intermolecular interactions.
Figure 10. (a) View down the ab plane, depicting the formation of a molecular sheet via weak C−H···F intermolecular interactions in 10. (b) The
packing of molecules down the ac plane, depicting C−H···π intermolecular interactions in 10.
to minimize the repulsion of the phenyl ring with the nitrogen
lone pair of electrons. The corresponding experimental torsion
angle lies in the range of 35−50° [except for compounds 2, 4, 5,
7, and 9 (polymorph II)] and are almost similar to that of N-
benzylideneaniline. Compounds 5 and 7 are nearly planar (high
energy conformation), and the stabilization essentially comes
from the positional disorder associated with the CN bond in
addition to the crystallographic disorder about the inversion
center associated with half of the molecule in the asymmetric
unit. For the torsion C1−C13−N1−C7, both the experimental
and theoretical values are close to planarity (Table 3).
The molecular packing in the crystal of N-benzylideneani-
line18d consists of the arrangement of the molecules with their
Figure 11. Packing of molecules via weak C−H···F and C−H···π
long axis parallel to the crystallographic a-axis [Figure 14]. The
substitution of the fluorine atom at ortho position in case of 12
completely alters the crystal structure (orthorhombic P212121)
in comparison to the unsubstituted one. It is of interest to note
that the substitution of the fluorine atom at the meta position in
N-benzylideneaniline (compound 11) did not alter the cell
parameters and close packing of molecules, hence displaying
isostructurality37 with the parent compound. The incorporation
of a fluorine atom at the para position on either phenyl ring
(compounds 10 and 13) has resulted in the formation of a
different crystal structure compared to the unsubstituted analogue.
Although the former (10) crystallizes in the monoclinic P21/n
space group, the lattice parameters and crystal packing were found
to be different than those of the parent compound, while the latter
intermolecular interactions in 11.
It is of active interest to compare the similarities and differ-
ences, which occur in the molecular conformation and the
crystal packing on substitution of the fluorine atom (responsible
for altered packing motifs) on the molecular skeleton containing
the N-benzylideneaniline moiety. The parent compound, N-
benzylideneaniline, was found to exist in the monoclinic P21/c
space group with Z = 4 [a = 12.1211(9) Å, b = 7.7182(5) Å, c =
11.8429(9) Å, β = 118.341(1)o].18d The conformational features
associated with these molecules in the solid state present some
interesting features when compared with the torsion values
obtained from theoretical calculations. For the torsion angle C6−
C1−C13−N1 the theoretical values are close to planarity. The
theoretical value for the torsion C8−C7−N1−C13 with respect
to the aniline ring remains essentially constant between 31−43°,
(13) crystallizes in triclinic P1. However compounds 10 and 13
̅
have similar packing, the relationship between the lattice param-
eters being a = a′; b = 2c′; c = b′ wherein a, b, c and a′, b′, c′ are
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Figure 12. (a) Packing view down the ab crystallographic plane via weak C−H···F and C−H···π intermolecular interactions in 12. (b) The weak
C−H···N and C−H···π interactions dictate the formation of a herringbone sheet down the bc plane in 12.
Figure 13. (a) Molecular sheet down the ac plane via bifurcated weak C−H···F intermolecular interactions in 13. (b) Packing of molecules in 13 via
weak C−H···π and C−H···N intermolecular interactions.
the lattice parameters of 10 and 13 respectively. Another
notable feature is the fact that compounds 1 (difluorinated) and
13 (monofluorinated) crystallize in an identical space group
and the orthorhombic form being non-centrosymmetric. Both
the forms exhibit positional disorder with respect to the position
of the CN bond and are distinguished in terms of the nature
of weak C−H···F hydrogen bonds in their crystal lattices.
The Cambridge Structural Database38 search39 has been
performed for N-benzylideneaniline derivatives to compare the
molecular conformation and crystal packing of related com-
pounds with the present series of compounds. Table 4 lists all
the related structures containing one functional group present
on either or both the phenyl rings. Crystal structures which
contain any strong hydrogen bond donor (e.g., hydroxyl and
amino groups) or acceptor (amino nitrogen and oxygen)
groups have not been considered [ETEYUX, LIXJIL, TIQRIU,
ZEXPEX, ZEXPEX01, ZEXPEX02].
(triclinic P1), 1 and 13 being essentially isostructural in the
̅
solid state [Figures 1b and 13b]. Compounds 1 and 13 are also
isostructural with 4-fluoro-N-(4-fluorophenyl)benzamide.8b It is
also important to note that the crystal packing of difluorinated
N-benzylideneanilines, namely, 2, 5, 7, 8, and 9 (polymorph I),
were found to be different from N-benzylideneanilines. Among
these as well, the crystal packing is found to be different from
each other as the supramolecular synthons observed in these
structures are different, except in the case of compounds 5 and
7, which exhibit isostructurality [Figures 5 and 7b]. It is also of
importance that 10 has double the unit cell volume of 5 or 7
and the crystal packing is also similar with the latter, the lattice
parameters being related by a = c′; b = a′; c = b′/2 where a, b, c
and a′, b′, c′ are the lattice parameters of 5/7 and 10 respec-
tively. Furthermore, it is to be noted that compounds 6 and 12
crystallized in the orthorhombic noncentrosymmetric P212121
space group and also exhibit isostructural behavior [Figures 6b
and 12b]. Compound 9 which consists of fluorine atoms in the
ortho position in both the phenyl rings crystallizes in two poly-
morphic forms, the monoclinic form being centrosymmetric
The bromo (BRZBRA),40a chloro (CBZCAN01),17a,b and
cyano (AMEREQ)40b analogues of 1 have been found to display
different crystal structures as compared to that of 1. The triclinic
form of the compound CBZCAN exists in a planar conforma-
tion, whereas the orthorhombic form CBZCAN01 exists in a
nonplanar conformation, which is disordered with respect to the
2-fold crystallographic axis. CBZCAN and compound 1 have a
different molecular conformation, the former being planar and
the latter nonplanar. The resulting crystal packing is different as
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Figure 14. Packing view of N-benzylideneanilines (NBA) down the ac-plane.
Table 4. List of Unit Cell Parameters and Torsion Angles of N-Benzylideneaniline and Its Derivatives Reported in the CSD
torsion angles
C8−C7−N1− C6−C1−C13− C1−C13−N1−
compound name CCDC REFCODE
space group; cell parameter
C13
56.83
N1
C7
179.51
N-benzylideneaniline BENZON10
(P21/c); 12.157, 7.921, 11.944, 118.38
9.92
1.14
p-cyano-N-(p-cyanobenzylidene)aniline
(P21/c); 4.727(0), 10.443(2), 11.943(2), 98.70(3)
1.14
180.00
AMEREQ
a
a
a
a
a
a
a
a
N-(p-Bromobenzylidene)-p-bromoaniline
BRZBRA
(P21/a); 24.912(13), 5.877(1), 4.046(1), 92.42(3)
2.20, 2.20
0.12, 0.12
2.20, 2.20
0.12, 0.12
180.00, 180.00
180.00, 180.00
179.38, 179.38
179.08
a
N-(p-chlorobenzylidene)-p-chloroaniline
CBZCAN
(P1); 5.986(2), 3.933(1), 12.342(2), 87.38(3), 78.40(3),
89.53(3)
a
a
a
N-(p-chlorobenzylidene)-p-chloroaniline
CBZCAN01
(Pccn); 24.503(5), 6.334(1), 7.326(1)
26.67, 26.67
0.48
26.67, 26.67
2.65
N-(p-chlorobenzylidene)-m-chloroaniline
RONKEK
(P21); 10.742(4), 4.820(2), 11.634(5), 109.25(2)
(P21);11.113(2), 4.796(2), 11.886(2), 109.55(3)
(P21); 11.030(2), 4.750(2), 11.670(2), 109.66(3)
(P21); 10.840(2), 4.740(2), 11.630(2), 108.57(3)
(P21/c); 8.609(6), 5.989(4), 23.437(14), 93.66(2)
(P21/c); 8.630(2), 6.050(2), 23.226(5), 92.34(3)
(P21/n); 25.231(6), 3.943(1), 12.002(3), 102.64(2)
(P212121); 9.615(2), 31.336(7), 3.967(2)
N-(p-bromobenzylidene)-m-bromoaniline
RONKIO
0.98
3.78
176.68
N-(p-bromobenzylidene)-m-chloroaniline
RONKOU
1.62
1.76
178.01
N-(p-chlorobenzylidene)-m-bromoaniline
RONKUA
0.15
3.15
179.16
N-(m-chlorobenzylidene)-p-bromoaniline
RONLAH
44.04
9.61
175.49
N-(m-bromobenzylidene)-p-bromoaniline
41.88
9.99
175.46
RONLEL
a
a
a
a
a
a
a
N-(m-chlorobenzylidene)-m-chloroaniline
WEMHUR
37.73, 23.09
17.02, 29.27
39.13
27.14, 12.85
30.15, 18.25
11.62
164.51, 166.57
179.56, 178.75
179.57
a
N-(m-chlorobenzylidene)-m-bromoaniline
WEMJAZ
N-(m-bromobenzylidene)-m-bromoaniline
WEMJED
(P212121); 9.646(3), 31.552(7), 4.007(2)
N-(m-bromobenzylidene)-m-chloroaniline
WEMJIH
(P212121); 7.842(3), 13.644(7), 11.096(7)
40.41
3.79
176.39
(E)-4-bromo-N-(2-chlorobenzylidene)aniline
EVONEJ
(P21/n); 15.243(13), 4.020(4), 20.142(18), 103.25(0)
43.46
5.99
176.77
a
Another torsion angle due to the presence of disorder around the CN bond.
they utilize different types of interactions. The former (chlorine
substitution at para position on both side) utilize Cl···Cl inter-
actions with no C−H···Cl contacts in crystal packing while the
latter have C−H···F hydrogen bonds only and no F···F contact.
Furthermore, substitution of other halogens, namely, bromo and
chloro [para to benzaldehyde side and meta to aniline side], does
not alter the crystal structure (monoclinic, non-centrosymmetric
P21) in most of the cases [RONKEK40c (Cl, p, m); RONKIO40c
(Br, p, m); RONKOU40c (Br, p; Cl, m); RONKUA40c (Cl, p; Br,
m)], the lattice parameters depicting isostructurality. In contrast,
the related fluoro compound 2 crystallizes in the monoclinic centro-
symmetric P21/c space group. In cases of related halogen substitu-
tion, meta to benzaldehyde side and para to aniline side, two
compounds RONLAH40c (Cl, m; Br, p), RONLEL40c (Br, m, p),
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crystallizes in the corresponding centrosymmetric monoclinic,
P21/c exhibiting isostructural behavior with Z′ = 1 (Table 4).
The related fluoro compound 4 crystallizes in the triclinic P1
with Z′ = 2 molecules in the asymmetric unit.
in the presence of other halogens on the N-benzylideneaniline
scaffold are currently in progress. The role of organic fluorine in
altering crystal structures in the presence of other halogens and
related functional groups will be the key focus aimed toward
an improved understanding of interhalogen interactions in the
solid state.
̅
Further, the comparison of crystal structures of other halogen
substituted N-benzylideneanilines [meta to both the benzalde-
hyde and aniline moieties] resulted in the following CSD
REFCODES. WEMHUR40d (Cl, m, m) (crystallizes in mono-
clinic P21/n) was found to be different than that of the related
halogenated analogue WEMJAZ40d (Cl, m; Br, m), WEM-
JED40d (Br, m, m), WEMJIH40d (Br, m; Cl, m), which crystal-
lized in the orthorhombic non-centrosymmetric P212121 space
group (Table 4). Among these only WEMJAZ and WEMJED
are found to be isostructural. The only reported analogue of
compound 7 in the CSD is 4-bromo-N-(2-chlorobenzylidene)
aniline (EVONEJ),40c and the crystal packing was found to be
completely different from the fluorinated compound (Table 4).
It is evident from the above-mentioned features of differently
substituted N-benzylidenanilines that the incorporation of
fluorine atoms in both the rings at different positions have
resulted in a variety of molecular structures, wherein positional
and crystallographic disorder play a significant role thereby
exhibiting conformational differences in the solid state. On
careful study of Table 2a, it may be noted that the C−H···F
hydrogen bonds having interaction energy >4 kcal/mol show
significant directionality (∠C−H···F > 160°) with one excep-
tion. These crystal structures display a variety of well-defined
supramolecular motifs, which steer the modified packing of
molecules utilizing those interactions involving “organic
fluorine” in the absence of strong hydrogen bond donors and
acceptors. These observations further provide evidence of the
directionality and the stabilizing influence of the C−F group in
altering the crystal packing through the presence of weak but
cooperative C−H···F hydrogen bonds. The packing is further
supported by weak C−H···π interactions involving an aromatic
ring and also the isolated double bond.
ASSOCIATED CONTENT
* Supporting Information
Crystallographic information file; melting point of solid
■
S
compounds determined from DSC data; results of CLP
1
calculations; dihedral angles; FTIR spectra, H NMR, DSC
traces of solids; powder X-ray data; profile fitting refinement
with the cell parameters for both the forms; ORTEP of all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*(A.R.C.) E-mail: angshurc@iisermohali.ac.in, phone: 0091-
172-2240266; (D.C.) E-mail: dchopra@iiserb.ac.in, phone:
0091-755-4092321.
Author Contributions
#These authors have contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
G.K. thanks CSIR, India, and P.P. thanks UGC, India, for a
research fellowship. A.R.C. and G.K. thank Dr. Kabirul Islam
for useful discussions. We thank IISER Mohali for Singe Crystal
X-ray and NMR facilities; IISER Bhopal for FTIR and DSC
measurements, and IISc Bangalore for PXRD measurements.
Both IISER Mohali and IISER Bhopal are acknowledged for
research and all other infrastructural facilities. D.C. thanks
DST-Fast track scheme for research funding.
CONCLUSION
■
In the current manuscript, we have shown the importance of
the C−F group in a series of mono- and difluorinated benzyl-
ideneanilines by single crystal X-ray diffraction studies per-
formed at low temperature. The N-benzylideneaniline molec-
ular skeleton allows for an evaluation of the changes which get
manifested when a fluorine atom is substituted on the phenyl
ring and its position is allowed to vary over the phenyl ring.
This electronic feature results in conformational changes in
different mono- and difluorinated benzylideneanilines, in addi-
tion to the presence of positional disorder in this class of
molecules. It is evident from the detailed analysis of the struc-
tures of these molecules and related compounds in the CSD
containing different halogens and other groups that there is a
delicate interplay of steric and electronic factors which govern
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the final molecular conformation and subsequent crystal packing
in these compounds. This also has implications in the serendi-
pitous phenomenon of polymorphism in the solid state. It is also
of importance to note that the aromatic C−F group(s) in the
absence of strong hydrogen bonding functional groups are
capable of significantly influencing the crystal structures of small
organic molecules. The interaction energy calculations show that
these hydrogen bonds have energies ranging from 1 to 5 kcal/mol.
Several supramolecular motifs (namely dimers and chains) based
on C−H···F hydrogen bonds have been observed in these struc-
tures. Our efforts to investigate the capability of “organic fluorine”
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