Role of intermolecular interactions involving organic fluorine in trifluoromethylated benzanilides

Article abstract of DOI:10.1039/c2ce06254b

Trifluoromethylated benzanilides, containing C(sp³)-F bonds, have been synthesized and their crystal and molecular structures have been investigated to highlight the significance of weak intermolecular interactions associated with the presence

Full text of DOI:10.1039/c2ce06254b

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PAPER
Role of intermolecular interactions involving organic fluorine in
trifluoromethylated benzanilides†
Piyush Panini and Deepak Chopra*
Received 22nd September 2011, Accepted 14th December 2011
DOI: 10.1039/c2ce06254b
3
Trifluoromethylated benzanilides, containing C(sp )–F bonds, have been synthesized and their crystal
and molecular structures have been investigated to highlight the significance of weak intermolecular
interactions associated with the presence of organic fluorine in a molecule. It is observed that the
molecular conformation and packing characteristics are a delicate interplay amongst different
intermolecular interactions, namely strong N–H/O]C, weak C–H/O]C, C–H/F–C, and C–H/
p H-bonds, along with C–F/F–C and C–F/p intermolecular interactions in the solid state. All the
isomers are associated with variations in crystal packing due to the presence of different
supramolecular variants introduced by the presence of a trifluoromethyl group at the ortho, meta and
para positions of the phenyl ring. Furthermore, a comparison of the experimental molecular
conformation with that obtained from DFT theoretical calculations delineates the significant role of the
trifluoromethyl group on the phenyl ring, which results in variations in conformational flexibility
associated with the molecule. It has been observed that the –CF
3
group is associated with rotational
disorder in some of the crystalline solids and the overall crystal structure is stabilized by a network of
2
3
3
3
C(sp )–H/F–C(sp ) intermolecular H-bonds and C–(sp )F/F–C(sp ) contacts [the ‘‘fluorous effect’’]
in the crystalline lattice. It is also observed that there also exists a definite relationship between the
acidity of the participating hydrogens with the hydrogen bonding characteristics of such weak C–H/
F–C H-bonds in the crystal.
8
a weak H-bond. The strength of the H-bond is influenced by the
Introduction
electronic environment around the fluorine atom (in terms of
hybridization of the carbon atom to which it is connected). Also
the acidity of the donor H-atom depends on the hybridization of
Non-covalent interactions have been found to play a pivotal role
1
in the self-assembly of molecules. Such interactions have been
2
well recognized in structural biology and chemistry. Traditional
9
the carbon atom to which it is connected. With this viewpoint,
non-covalent forces include hydrogen bonds which are strong
3
and have been well understood. In recent years, the focus has
aimed towards an understanding of intermolecular interactions
in solids containing a trifluoromethyl group, we have synthesized
a series of isomeric mono- and di-trifluoromethylated benzani-
lides. The importance of the trifluoromethyl group in crystal
engineering has been investigated in diketoarylhydrazones
wherein the compounds have been analysed for packing motifs in
shifted towards the understanding of weaker non-covalent
4
interactions which are flexible, directional and cooperative. In
this regard, in addition to the now well understood C–H/O/N
5
hydrogen bonds, the evaluation of the role of weak interactions
involving halogens (C–H/X–C), in particular organic fluorine is
6
of extreme interest. It was documented that fluorine being highly
7
non-polarisable cannot participate in H-bond formation, but
10
the crystal. The role of a fluorine atom directly connected to the
phenyl ring has already been investigated in related isomeric
11
benzanilides. In this study, we investigate the role of the tri-
active research inputs in this area in the past two decades have
2
finally established the stabilizing role of weak C(phenyl, sp )–
fluoromethyl group, present on the benzanilide framework, and
evaluate the changes in molecular conformation and packing
interactions due to the participation of this moiety in crystal
formation. Subsequently, it is of interest to evaluate the changes
in molecular conformation and crystal packing which accom-
2
H/F–C(sp , phenyl) interactions. This is now classified as
Department of Chemistry, Indian Institute of Science Education and
Research Bhopal, ITI (Gas Rahat) Building, Govindpura, Bhopal,
3
pany the replacement of a –F by a –CF moiety at the o-, m- and
4
4
†
62023, India. E-mail: dchopra@iiserbhopal.ac.in; Fax: +91-755-
092392; Tel: +91-755-4092321
Electronic supplementary information (ESI) available. CCDC
p-positions on either or both of the phenyl rings in this class of
compounds.
In addition to C–H/X and C–X/X–C interactions, the lone
reference numbers 826193–826201 and 843875. For ESI and
crystallographic data in CIF or other electronic format see DOI:
1
12
pair–p interaction (C–X/p) has been recognized as a very
important supramolecular entity and this aspect has been
0.1039/c2ce06254b
1
972 | CrystEngComm, 2012, 14, 1972–1989
This journal is ª The Royal Society of Chemistry 2012

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1
3
highlighted in recent reviews. The importance of the CF3
The –CF substituted aniline (1.1 equiv.) and dimethylamino-
3
groups has already been realized in different fields of physics,
pyridine (1.2 equiv.) were taken in a round bottomed flask con-
taining dry dichloromethane (15 ml). The round bottomed flask
was closed with a septum to ensure a dry atmosphere using
a nitrogen balloon. The reaction setup was then put over an ice
14
biology and chemistry. The spatial demand and polarity of the
15
3
CF groups affect protein folding. The stability is due to
a general increase in hydrophobicity and it has been proposed in
non-canonical acids that formation of specific F/F interactions
or the ‘‘fluorous effect’’ increases the structural stability of
hydrophobic protein domains. The stabilizing influence of these
interactions overcompensates for the destabilizing impact of
enhanced steric demands and hence electrostatics become more
important than volume. These characteristics have been further
studied using molecular dynamics (MD) simulation to under-
stand the behaviour and role of these groups in molecular and
3
bath and –CF substituted benzoyl chloride (1 equiv.) was added
drop wise into the reaction mixture with constant stirring. The
reaction mixture was then allowed to come to RT and was left as
such for 8–10 hours. Completion of the reaction was monitored
with TLC. At the end of the reaction, the reaction mixture was
quenched with 5% hydrochloric acid, extracted with dichloro-
methane, driedusingsodiumsulfate andfinally purifiedbycolumn
chromatography. Allthesynthesizedcompoundsweretakenin5.0
ml beakers and dissolved in different combinations of polar and
non-polar solvents, covered with parafilm, perforated and kept
16
biological recognition processes in 1,1,1-trifluoropropan-2-ol.
The –CF group being strongly electron-withdrawing in nature
3
ꢀ
affects the nature of hydrogen atoms present in its vicinity which
participate in H-bond formation. This subsequently affects bio-
logical recognition processes and can modify the behaviour from
at low temperature [0 C] to obtain single crystals of desired size
and quality. The different solvent combinations chosen were
dichloromethane/hexane, chloroform/hexane, ethyl acetate/
hexane, methanol/hexane, acetonitrile/hexane, ethanol/hexane,
and acetone/hexane. Morphologies ranging from thin plates,
blocks to fibrous needles were obtained. The product was further
characterized by experimental powder X-ray data along with
simulated powder patterns [Fig. S1(a)–(o)†]. In order to establish
thephasepurity, theexperimental profiles forthe recordedpowder
17
agonists to antagonists. With the stereoelectronic control of
CF being much more dominant than methyl, the presence of this
group has a profound influence on the in vitro antimalarial
3
18
activity as observed in indole derivatives, the reason being the
increased lipophilicity and hence enhanced drug permeability.
The importance of fluorine interactions has also been observed in
crystals of tetrathiafulvalene derivatives wherein fluorine segre-
gation stabilizes crystal packing and controls [2 + 2] cycloaddi-
27
diffraction patterns were refined using the program JANA 2000.
The profile fitting parameters R and Rwp have also been included
p
19
tion reactions in the solid state. The trifluoromethyl group has
in the above-mentioned diagrams. The higher values of these
refinement parameters (observed in the case of T-0-3, T-1-1, T-2-2
and T-3-1) indicate the possibility of the presence of more than one
phase [Fig. S1(a)–(o)†]. Such studies, directed towards the inves-
tigation of polymorphism in this class of compounds, are currently
in progress. In addition the synthesized compounds were charac-
terized by IR [Fig. S2 (a)–(o)†] and proton NMR [Fig. S3 (a)–(o)†]
spectroscopy. The list of dihedral angles is included in Table S1†.
Scheme 1 describes all obtained isomeric molecules and the
method of nomenclature used in this study.
also been proven to be a steering agent in the topochemical [2 +
2
0
2
] photodimerization reactions, and the significance of this
functional group is realized in magnetic properties of transition
2
1,22
23
conformational disorder, phase transi-
26
metal complexes,
24,25
tions
and polymorphism in organic solids.
In the light of the above-mentioned versatility associated with
the presence of trifluoromethyl groups, it is of interest to
systematically investigate the contributing role of the CF group
3
in small organic molecules, containing an invariant molecular
framework, namely the benzanilides.
Melting points, synthesized yields, and spectroscopic
1
characterization (FTIR, H NMR) of the synthesized compounds
Experimental section
1
.
N-Phenyl-2-(trifluoromethyl)benzamide (T-0-1). Melting
ꢁ1
Synthesis, characterization and crystal growth
ꢀ
point: 158–160 C; yield: 94%, FTIR (in cm : KBr): 3282, 1650;
1
H NMR (400 MHz, CDCl
The starting materials trifluoromethyl substituted anilines (ortho,
meta, and para), trifluoromethyl substituted benzoyl chlorides
3
): d 7.20 (t, J ¼ 7.45 Hz, 1H), 7.39 (t,
J ¼ 7.96 Hz, 2H), 7.62 (m, 6H), 7.76 (d, J ¼ 7.62, 1H).
(
ortho, meta, and para), and dimethylaminopyridine (DMAP)
were purchased from Sigma Aldrich (Analytical Grade) and were
used directly from the bottle. The solvent dichloromethane, used
for the reaction, was dried using calcium hydride and stored over
molecular sieves. The solvents used for crystallization were of
analytical grade.
2. N-Phenyl-3-(trifluoromethyl)benzamide (T-0-2). Melting
ꢁ1
ꢀ
point: 150–151 C, yield: 93%, FTIR (in cm : KBr): 3248, 1651;
1
H NMR (400 MHz, CDCl
3
): d 7.21 (t, J ¼ 7.47 Hz, 1H), 7.41 (t,
J ¼ 7.82 Hz, 1H), 7.65 (m, 3H), 7.83 (d, J ¼ 7.82 Hz, 1H), 7.95 (s,
1H), 8.07 (d, J ¼ 7.93 Hz, 1H), 8.14 (s, 1H).
Scheme 1 Synthetic procedure for the preparation of isomeric trifluoromethylated benzanilides and IUPAC nomenclature. T–A–B [A and B denote the
two substituted phenyl rings]; A or B ¼ 0 [no substitution on that ring]; A or B ¼ 1, 2, 3 [o, m, p substitution on that ring respectively].
This journal is ª The Royal Society of Chemistry 2012
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3
.
N-Phenyl-4-(trifluoromethyl)benzamide (T-0-3). Melting
ꢁ1
13. 2-(Trifluoromethyl)-N-[4-(trifluoromethyl)phenyl]ben-
ꢀ
ꢀ
point: 218–220 C; yield: 94%; FTIR (in cm : KBr): 3347, 1654;
1
zamide (T-3-1). Melting point: 168–170 C; yield: 93%; FTIR (in
ꢁ1
1
cm : KBr): 3252, 1651; H NMR (400 MHz, CDCl ): d 7.65 (m,
H NMR (400 MHz, CDCl ): d 7.68 (d, J ¼ 8.61 Hz, 2H); 7.81 (d,
3
3
J ¼ 8.38 Hz, 5H), 7.96 (s, 1H), 8.02 (d, J ¼ 8.27 Hz, 2H).
5H), 7.70 (s, 1H), 7.74 (d, J ¼ 8.58 Hz, 2H), 7.78 (d, J ¼ 7.62 Hz,
1
H).
4
.
N-[2-(Trifluoromethyl)phenyl]benzamide (T-1-0). Melting
ꢁ1
ꢀ
point: 143–145 C; yield: 92%; FTIR (in cm : KBr): 3207, 1644;
14. 3-(Trifluoromethyl)-N-[4-(trifluoromethyl)phenyl]ben-
ꢀ
1
H NMR (400 MHz, CDCl
J ¼ 7.35 Hz, 2H), 7.65 (m, 3H), 7.91 (d, J ¼ 7.07 Hz, 2H), 8.27 (s,
H), 8.47 (d, J ¼ 8.18 Hz, 1H).
3
): d 7.29 (t, J ¼ 7.60 Hz, 1H), 7.55 (t,
zamide (T-3-2). Melting point: 147–149 C; yield: 91%; FTIR (in
1
ꢁ1
3
cm : KBr): 3252, 1652; H NMR (400 MHz, CDCl ): d 7.68 (t,
1
J ¼ 7.72 Hz, 3H), 7.81 (d, J ¼ 8.50 Hz, 2H), 7.86 (d, J ¼ 7.87 Hz,
1
H), 8.05 (s, 1H), 8.09 (d, J ¼ 7.84 Hz, 1H), 8.15 (s, 1H).
5
.
2-(Trifluoromethyl)-N-[2-(trifluoromethyl)phenyl]benza-
ꢀ
mide (T-1-1). Melting point: 152–154 C; yield: 91%; FTIR (in
15. 4-(Trifluoromethyl)-N-[4-(trifluoromethyl)phenyl]ben-
ꢀ
ꢁ
1
1
cm : KBr): 3233, 1660; H NMR (400 MHz, CDCl ): d 7.34 (t,
zamide (T-3-3). Melting point: 222–224 C; yield: 93%; FTIR (in
1
3
ꢁ1
J ¼ 7.72 Hz, 1H), 7.69 (m, 6H), 7.81 (d, J ¼ 7.71 Hz, 1H), 8.31 (d,
J ¼ 8.18 Hz, 1H).
3
cm : KBr): 3325, 1661; H NMR (400 MHz, CDCl ): d 7.68 (d,
J ¼ 8.79 Hz, 2H), 7, 81 (d, J ¼ 8.21 Hz, 4H), 7.96 (s, 1H), 8.02 (d,
J ¼ 7.79 Hz, 2H).
6
.
3-(Trifluoromethyl)-N-[2-(trifluoromethyl)phenyl]benza-
ꢀ
mide (T-1-2). Melting point: 116–118 C; yield: 91%; FTIR (in
1
Crystallography
ꢁ1
3
cm : KBr): 3228, 1644; H NMR (400 MHz, CDCl ): d 7.34 (t,
Single crystal X-ray diffraction data were collected on CrysAlis
CCD Xcalibur, Eos (Nova), Oxford Diffraction, with an X-ray
generator operating at 50 kV and 1 mA, using MoKa radiation
J ¼ 7.70 Hz, 1H), 7.69 (m, 3H), 7.88 (d, J ¼ 7.80 Hz, 1H), 8.04 (d,
J ¼ 7.89 Hz, 1H), 8.22 (m, 2H), 8.39 (d, J ¼ 8.25 Hz, 1H).
ꢀ
28
(
l ¼ 0.7107 A). All the crystal structures were solved by direct
7
.
4-(Trifluoromethyl)-N-[2-(trifluoromethyl)phenyl]benza-
ꢀ
29
methods using SIR 92 and refined by the full matrix least
mide (T-1-3). Melting point: 138–140 C; yield: 94%; FTIR
30
ꢁ1
1
squares method using SHELXL97 present in the program suite
(
in cm : KBr): 3206, 1644; H NMR (400 MHz, CDCl
d 7.34 (t, J ¼ 7.6 Hz, 1H), 7.68 (m, 2H), 7.82 (d, J ¼ 8.14 Hz,
H), 8.01 (d, J ¼ 8.14 Hz, 2H), 8.23 (s, 1H), 8.41 (d, J ¼ 8.33
Hz, 1H).
3
):
31
WinGX. ORTEP diagrams of all the compounds were gener-
32
ated using ORTEP32 and packing diagrams were generated
34
using CAMERON and Mercury software. Geometrical
2
33
35
36
calculations were done using PARST and PLATON.
8
.
N-[3-(Trifluoromethyl)phenyl]benzamide (T-2-0). Melting
ꢁ1
ꢀ
Refinement protocol for the disordered trifluoromethyl group
point: 110–112 C; yield: 94%; FTIR (in cm : KBr): 3317, 1652;
1
H NMR (400 MHz, CDCl ): d 7.42 (d, J ¼ 7.78 Hz, 1H), 7.50
3
The non-hydrogen atoms were refined with anisotropic
displacement parameters and hydrogen atoms were located from
a difference Fourier map and refined with isotropic displacement
(
(
m, 3H), 7.59 (t, J ¼ 7.40 Hz, 1H), 7.89 (m, 3H), 7.96 (s, 1H), 8.08
s, 1H).
parameter. The CF
3
group in molecules T-1-1, T-2-0, T-3-1, T-3-
9
.
2-(Trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]benza-
ꢀ
2
and T-3-3 was found to be rotationally disordered around two
mide (T-2-1). Melting point: 114–117 C; yield: 93%; FTIR (in
independent orientations. The occupancy of disordered fluorines
at two orientations was refined by using PART command in
SHELXL97. There are many related structures containing
a disordered trifluoromethyl group wherein the disorder is
ꢁ
1
1
cm : KBr): 3272, 1667; H NMR (400 MHz, CDCl
J ¼ 7.79 Hz, 1H), 7.51 (t, J ¼ 7.92 Hz, 1H), 7.64 (m, 3H), 7.76 (m,
H), 7.82 (d, J ¼ 7.98 Hz, 1H), 7.88 (s, 1H).
3
): d 7.45 (d,
2
37
present over two or more sites in the crystal structure.
1
0. 3-(Trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]ben-
ꢀ
zamide (T-2-2). Melting point: 123–125 C; yield: 92%; FTIR (in
Results
ꢁ
1
1
cm : KBr): 3280, 1652; H NMR (400 MHz, CDCl ): d 7.46 (d,
3
J ¼ 7.79 Hz, 1H), 7.88 (m, 2H), 7.96 (s, 1H), 8.04 (s, 1H), 8.09 (d,
J ¼ 7.79 Hz, 1H), 8.15 (s, 1H).
Table 1 lists all crystallographic and refinement data. Intra- and
intermolecular interactions are listed in Tables 2 and 3. The
geometrical restrictions placed on the intermolecular H-bonds or
ꢀ
contacts are the sum of the van der Waals radii +0.4 A and
38
1
1. 4-(Trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]ben-
ꢀ
ꢀ
zamide (T-2-3). Melting point: 128–130 C; yield: 94%; FTIR (in
directionality greater than 110 . Table 4 lists a comparison of the
ꢁ
1
1
cm : KBr): 3297, 1660; H NMR (400 MHz, CDCl
3
): d 7.46 (d,
unit cell parameters in fluorinated benzanilides with tri-
fluoromethylated benzanilides. DFT calculations at the B3LYP/
J ¼ 7.83 Hz, 1H), 7.53 (t, J ¼ 7.97 Hz, 1H), 7.78 (d, J ¼ 8.20 Hz,
39
2
2
H), 7.88 (d, J ¼ 8.13 Hz, 1H), 7.96 (s, 1H), 8.00 (d, J ¼ 8.13 Hz,
6-31G** were performed using TURBOMOLE with crystal-
lographic coordinates as a starting set (only the major conformer
for the trifluoromethyl group was introduced in the calculations)
to obtain the optimized geometry of an isolated molecule
and selected torsion angles obtained from theoretical calcula-
tions were compared with the experimentally obtained values
(Table 5).
H), 8.06 (s, 1H).
1
2. N-[4-(Trifluoromethyl)phenyl]benzamide (T-3-0). Melting
ꢁ1
ꢀ
point: 216–218 C; yield: 91%; FTIR (in cm : KBr): 3296, 1661;
1
H NMR (400 MHz, CDCl ): d 7.54 (m, 2H), 7.64 (m, 3H), 7.81
3
(
d, J ¼ 8.45 Hz, 2H), 7.91 (m, 2H), 7.96 (s, 1H).
974 | CrystEngComm, 2012, 14, 1972–1989
1
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Table 1 Crystallographic and refinement data
Data
Formula
T-0-1
C
T-0-3
C
T-1-0
C
T-1-1
C H F NO
15 9 6
14
H
F
10 3
NO
14
H
F
10 3
NO
14
H
10
F
3
NO
Formula weight
Temperature/K
Wavelength
CCDC no.
Solvent system
265.23
120
0.7107
826193
Dichloromethane
and hexane (1 : 1)
Monoclinic
265.23
120
0.7107
826194
Dry dichloromethane
265.23
120
333.23
120
0.7107
843875
Chloroform and hexane
(1 : 1)
Monoclinic
C2/c
21.2145(13)
6.7790(3)
9.7179(5)
90
100.886(5)
90
1372.41(13)
4
1.613
0.7107
826195
Dichloromethane and hexane
(1 : 2)
Tetragonal
P4
Crystal system
Space group
Triclinic
ꢁ
P1
5.359(5)
7.714(5)
14.242(5)
77.099(5)
81.606(5)
89.607(5)
567.5(7)
2
1.552
P2
1
/c
1
ꢀ
a/A
9.991(5)
16.421(5)
15.645(5)
90
108.492(5)
90
2434.2(16)
8
1.447
0.123
1088
9.052(5)
9.052(5)
15.156(5)
90
90
90
1241.9(11)
4
1.419
0.120
544
2.62, 29.33
(ꢁ12, 12), (ꢁ12, 12),
(ꢁ20, 20)
Refined all
14 952
ꢀ
b/A
ꢀ
c/A
a/
ꢀ
ꢀ
b/
ꢀ
g/
Volume
Z
Density/g cm
m/mm
F (000)
q (min, max)
ꢁ
3
ꢁ
1
0.132
272
0.157
672
2.48, 25.00
(ꢁ11, 11), (ꢁ19, 19),
2.71, 29.11
(ꢁ7, 7), (ꢁ10, 10), (ꢁ18, 19)
3.16, 29.27
(ꢁ28, 26), (ꢁ9, 9), (ꢁ13, 13)
hmin,max, kmin,max, lmin,max
(
ꢁ18, 18)
Treatment of hydrogens
No. of refl. measured
No. unique refl./obs. refl.
No. of parameters
Refined all
23 559
Refined all
12 667
2778, 2238
212
Refined all
7914
1717, 1242
166
4277, 3517
423
3075, 2583
212
R_all, R_obs
0.0663, 0.0551
0.1300, 0.1276
ꢁ0.269, 0.234
1.269
0.052, 0.040
0.1078, 0.1037
ꢁ0.230, 0.398
1.093
0.0438, 0.0334
0.0742, 0.0714
ꢁ0.212, 0.157
1.014
0.0730, 0.0481
0.1282, 0.1106
ꢁ0.237, 0.230
1.032
2 2
wR _all, wR _obs
ꢀ
ꢁ3
Drmin,max/eA
G.o.F
Data
Formula
T-2-0
H
10
T-2-1
C
T-2-2
C H F NO
15 9 6
C
14
F
3
NO
15
H
9
F
6
NO
Formula weight
Temperature
Wavelength
265.23
120
0.7107
826196
333.23
120
0.71073
826197
333.23
120
0.71073
826198
CCDC no.
Solvent system
Crystal system
Space group
Dichloromethane and hexane (1 : 2)
Monoclinic
Chloroform and hexane (1 : 1)
Orthorhombic
Pna2
9.034(5)
13.743(5)
11.372(5)
90
90
90
1411.9(11)
4
1.568
0.153
672
2.70, 32.85
(ꢁ13, 13), (ꢁ20, 20), (ꢁ17, 16)
Refined all
22 894
4880, 4062
244
Acetonitrile and hexane (1 : 1)
Monoclinic
P2 /c
1
12.059(5)
12.540(5)
8.884(5)
90
91.804(5)
90
1342.8(11)
4
1.648
P2
1
/c
13.8471(4)
1
ꢀ
a/A
ꢀ
b/A
8.6097(2)
10.0943(3)
90
100.131(3)
90
1184.67(6)
4
1.487
ꢀ
c/A
a/
ꢀ
ꢀ
b/
ꢀ
g/
Volume
Z
Density/g cm
m/mm
F (000)
q (min, max)
ꢁ
3
ꢁ
1
0.126
544
0.161
672
2.80, 32.84
(ꢁ21, 20), (ꢁ12, 12), (ꢁ15, 14)
Refined all
19 628
4111, 3074
240
2.34, 32.76
(ꢁ17, 17), (ꢁ19, 18), (ꢁ12, 13)
Refined all
22 116
4633, 2814
244
hmin,max, kmin,max, lmin,max
Treatment of hydrogens
No. of refl. measured
No. unique refl./obs. refl.
No. of parameters
R_all, R_obs
0.0706, 0.0492
0.1297, 0.1127
ꢁ0.320, 0.329
1.031
0.0502, 0.0399
0.1047, 0.1008
ꢁ0.251, 0.243
1.023
0.1001, 0.0539
0.1371, 0.1244
ꢁ0.327, 0.531
1.012
2 2
wR _all, wR _obs
ꢀ
ꢁ3
Drmin,max/eA
G.o.F
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Table 1 (Contd.)
Data
Formula
T-3-1
T-3-2
T-3-3
C H F NO
15 9 6
C
15
H
9
F
6
NO
C
15
H
9
F
6
NO
Formula weight
Temperature
Wavelength
CCDC no.
Solvent system
Crystal system
Space group
333.23
120(2)
0.71073
826199
333.23
120(2)
0.71073
826200
333.23
120(2)
0.71073
826201
Methanol and hexane (1 : 1)
Monoclinic
P2 /n
1
5.2019(3)
14.3865(7)
18.1844(9)
90
97.367(5)
90
1349.63(12) 90
Dichloromethane and hexane (1 : 1)
Monoclinic
Dichloromethane and hexane (1 : 2)
Orthorhombic
Pccn
25.559(5)
11.622(5)
9.509(5)
90
90
P2
1
/n
12.8346(8)
ꢀ
a/A
ꢀ
b/A
8.061(5)
14.155(5)
90
108.350(5)
90
1390.0(11)
ꢀ
c/A
a/
ꢀ
ꢀ
b/
ꢀ
g/
Volume
90
2825(2)
Z
Density/g cm
m/mm
F (000)
q (min, max)
4
1.592
0.155
672
8
1.567
0.153
1344
4
1.640
0.160
672
ꢁ
3
ꢁ
1
2.59, 32.81
(ꢁ18, 19), (ꢁ11, 12), (ꢁ20, 21)
Refined all
23 224
4769, 2610
272
2.88, 29.32
(ꢁ35, 34), (ꢁ16, 16), (ꢁ11, 12)
Refined all
30 904
3591, 2564
257
2.67, 24.99
(ꢁ6, 6), (ꢁ17, 16), (ꢁ21, 21)
Refined all
12 483
2372, 1707
272
hmin,max, kmin,max, lmin,max
Treatment of hydrogens
No. of refl. measured
No. unique refl./obs. refl.
No. of parameters
R_all, R_obs
0.0976, 0.0445
0.1157, 0.1031
ꢁ0.255, 0.277
0.976
0.0783, 0.0538
0.1572, 0.1461
ꢁ0.519, 0.657
1.100
0.0851, 0.0568
0.1504, 0.1331
ꢁ0.295, 0.602
1.083
2 2
wR _all, wR _obs
ꢀ
ꢁ
Drmin,max/e A )
G.o.F
1
Structure of T-0-1
2 Structure of T-0-3
ꢁ
The molecule [Fig. 1(a)] crystallizes in a centrosymmetric
The crystal structure is centrosymmetric, the space group P1 with
Z ¼ 2. A strong N–H/O]C hydrogen bond along with
a C–H/O]C H-bond generates a molecular chain along the
a-axis [Fig. 2(b)]. The packing in crystal also involves the pres-
ence of weak F/F interactions (involving F2 and F3), acting
across the center of symmetry [Fig. 2(b)]. Fig. 2(c) shows
generation of a layer motif utilizing C–H/p intermolecular
monoclinic space group P2 /c with two molecules in the
1
asymmetric unit [molecules A and B], thus having Z ¼ 8. The
0
0
two molecules are connected with N–H/O ]C and C–H/
0
0
O ]C (involving H12) hydrogen bonds and the structure is
also stabilized by an intramolecular C8–H8/O1 hydrogen
bond. It is indeed noteworthy that the two molecules in the
asymmetric unit are stabilized by intramolecular C–F: (lone
pair)/p interactions, the lone pair being electronically more
available due to the absence of delocalization (not connected to
2
interactions which are connected through weak C(sp )–H/F–
C(sp ) H-bonds (involving H10 with F3), bifurcated C–H/F
(involving F2 with H10 and H3) weak H-bonds and a dimeric
3
2
2
3
the sp carbon or aromatic ring) with the relatively electron
motif formed by C(sp )–H/F–C(sp ) across the center of
symmetry (involving H3 and F2). The C–H/ p interactions
also stabilize the space between the chain of molecules formed via
N–H/O]C H-bonds [Fig. 2(c)].
deficient aryl ring (Cg1). The asymmetric unit is connected
along the crystallographic a-axis with strong N–H/O]C
hydrogen bonds [Fig. 1(b)] and forms molecular chains with
/ABABAB/ kind of arrangement. The packing of molecules
on viewing down the bc plane depicts formation of a herring-
3
Structure of T-1-0
2
3
bone sheet with involvement of C(sp )–H/F–C(sp ) and C–
H/p weak H-bonds [Fig. 1(c)] which stabilize the crystal
structure. Among all, C–H/F hydrogen bonds involving H9,
The molecule [Fig. 3(a)] crystallizes in the non-centrosymmetric
tetragonal space group P4
1
with Z ¼ 4. Strong N–H/O]C
0
0
3
H11, H10 , and H11 propagate along the b-axis, utilizing the
0
along with C–H/O]C H-bond and C(sp )–F/O]C forms
a helical assembly along the c-axis utilizing the 4 screw axis as
1
2
1
screw axis of symmetry, while interactions involving H4, H4
0
and H9 utilize the c-glide plane in packing, along with C–H/
element of symmetry [Fig. 3(b)]. The chain is further stabilized
40
by involvement of C–H/p intermolecular H-bonds
[involving H4 and H8 with Cg1 and Cg2] [Fig. 3(c)]. The
0
p (involves H3 which is the most acidic hydrogen ortho to
the trifluoromethyl group) interaction to build up the packing
of molecules along the crystallographic c-axis. It is of
interest to note that out of six fluorine atoms (the presence
of two ordered trifluoromethyl groups in the asymmetric unit,
one per molecule), five fluorine atoms participate in well-
2
3
helical chains are linked via a C(sp )–H/F-C(sp ) weak
hydrogen bond (involving H3 with F3 and H5 forming bifur-
cated H-bonds with both F1 and F2) [Fig. 3(d)]. It is note-
worthy that H11 is the most acidic hydrogen (due to the strong
electron-withdrawing effect of the adjacent trifluoromethyl
2
3
defined C(sp )–H/F–C(sp ) hydrogen bonds in the crystal
lattice.
ꢀ
group) and forms short [2.53(2) A] and highly directional
1
976 | CrystEngComm, 2012, 14, 1972–1989
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Table 2 Intra- and intermolecular interactions: Cg1 and Cg2 refer to the center of gravity of the ring formed by C1–C6 and C7–C12 respectively
ꢀ
D–H/A
ꢀ
ꢀ
ꢀ
:D–H/A/
D—H/A
T-0-1 (P2
D/A/A
H/A/A
Symmetry
1
/c, Z ¼ 8)
0
N1–H1/O1
C12–H12/O1
C8–H8/O1
0.98(5)
0.91(4)
0.97(4)
0.80(4)
1.03(4)
0.92(3)
0.97(4)
1.01(4)
1.02(4)
0.93(5)
1.00(5)
0.91(3)
1.346(4)
2.840(4)
3.310(5)
2.913(4)
2.859(4)
3.326(4)
3.476(4)
3.263(4)
3.529(5)
3.325(4)
3.453(4)
3.369(5)
3.701(4)
4.155(5)
1.89(5)
2.58(4)
2.33(4)
2.15(4)
2.68(4)
2.73(3)
2.53(4)
2.85(4)
2.70(3)
2.89(4)
2.69(4)
2.86(3)
3.320(3)
164(4)
138(3)
118(3)
147(3)
120(3)
139(3)
132(3)
125(3)
120(3)
121(4)
125(3)
156(2)
120(2)
x, y, z
x, y, z
x, y, z
x ꢁ 1, y, z
0
0
0
N1 –H1 /O1
0
C9–H9/F3
C11–H11/F3
C4–H4/F1
ꢁx + 1, y ꢁ ½, ꢁz + 3/2
ꢁx + 1, y ꢁ ½, ꢁz + 3/2
x, ꢁy + ½, z + ½
x, ꢁy + ½, z + ½
x ꢁ 1, ꢁy + ½, +z ꢁ ½
ꢁx, y ꢁ ½, ꢁz + 3/2
ꢁx, y ꢁ ½, ꢁz + 3/2
x, ½ ꢁ y, ½ + z
0
0
0
C4 –H4 /F1
0
0
C9 –H9 /F3
C10 –H10 /F3
0
0
0
0
0
0
C11 –H11 /F1
0
0
C3 –H3 /Cg2
0
0
C14 –F2 /Cg1
x, y, z
T-0-3 (P-1, Z ¼ 2)
C8–H8/O1
0.94(2)
0.90(2)
0.98(2)
0.96(2)
0.96(2)
0.95(2)
0.96(2)
0.98(2)
0.94(2)
0.96(2)
2.924(2)
3.147(3)
3.313(2)
3.439(2)
3.434(2)
3.652(2)
3.519(4)
3.500(4)
3.542(4)
3.531(4)
2.44(2)
2.31(2)
2.60(2)
2.64(2)
2.71(2)
2.84(2)
2.79(2)
2.75(2)
2.88(2)
2.86(2)
112(1)
154(2)
130(1)
141(1)
133(1)
143(1)
134(1)
134(1)
129(1)
128(1)
x, y, z
x + 1, y, z
x + 1, y, z
x, y, z ꢁ 1
N1–H1/O1
C12–H12/O1
C10–H10/F2
C10–H10/F3
C3–H3/F2
C2–H2/Cg2
C5–H5/Cg2
C8–H8/Cg1
C11–H11/Cg1
x + 1, y, z ꢁ 1
ꢁx + 1, ꢁy, ꢁz + 2
1 ꢁ x, 2 ꢁ y, 1 ꢁ z
ꢁx, 1 ꢁ y, 1 ꢁ z
1 ꢁ x, 1 ꢁ y, 1 ꢁ z
ꢁx, 2 ꢁ y, 1 ꢁ z
T-1-0 (P4
1
, Z ¼ 4)
N1–H1/O1
C3–H3/O1
C6–H6/O1
C11–H11/F3
C5–H5/F1
0.84(2)
0.98(2)
0.99(2)
0.94(2)
1.01(2)
1.01(2)
0.98(2)
0.94(2)
0.94(2)
2.825(2)
3.590(3)
3.159(2)
3.435(2)
3.477(2)
3.839(2)
3.310(2)
3.778(3)
3.526(3)
2.00(2)
2.63(2)
2.44(2)
2.53(2)
2.70(2)
2.87(2)
2.71(2)
2.97(2)
2.94(2)
166(2)
167(1)
129(1)
163(2)
133(2)
160(2)
120(1)
144(1)
122(2)
y, ꢁx, z ꢁ ¼
y ꢁ 1, ꢁx, z ꢁ ¼
y, ꢁx, z ꢁ ¼
ꢁy + 1, x, z + ¼
ꢁx, ꢁy + 1, z ꢁ ½
ꢁx, ꢁy + 1, z ꢁ ½
x ꢁ 1, y, z
C5–H5/F2
C3–H3/F3
C4–H4/Cg1
C8–H8/Cg2
T-1-1 (C2/c, Z ¼ 4)
N1–H1/O1
C4–H4/O1
C4–H4/O1
C3–H3/F2A
C2–H2/F1A
C3–H3/F1A
C7–F2B/Cg1
y, 1 ꢁ x, ꢁ¼ + z
y, ꢁx, ꢁ¼ + z
0.94(5)
0.98(2)
0.98(2)
0.96(2)
0.96(2)
0.96(2)
1.371(6)
2.851(14)
3.822(3)
3.721(3)
3.336(5)
3.431(8)
3.279(8)
4.173(2)
1.96(5)
2.86(2)
2.91(2)
2.61(2)
2.72(2)
2.66(2)
3.204(13)
158(4)
169(2)
141(2)
133(2)
132(2)
123(2)
127(1)
ꢁx, y, ꢁz + 3/2
x, ꢁy + 1, z ꢁ ½
ꢁx, ꢁy + 1, ꢁz + 1
x, ꢁy + 1, z ꢁ ½
ꢁx + ½, y + ½, ꢁz + 3/2
ꢁx + ½, ꢁy + ½, ꢁz + 1
x, ꢁy, z + ½
T-2-0 (P2
C8–H8/O1
1
/c, Z ¼ 4)
0.94(2)
0.87(2)
0.99(2)
1.01(2)
0.97(2)
0.96(2)
0.99(2)
0.99(2)
0.96(2)
1.317(6)
1.310(7)
2.859(2)
2.937(1)
3.287(1)
3.512(2)
3.592(9)
3.776(9)
3.546(9)
3.462(5)
3.543(7)
4.651(2)
4.651(2)
2.28(2)
2.13(2)
2.61(2)
2.80(2)
2.80(2)
2.85(2)
2.65(2)
2.53(2)
2.76(2)
3.358(8)
3.364(10)
119(1)
156(2)
125(1)
128(1)
139(1)
164(1)
151(1)
157(1)
139(1)
167.0(5)
167.2(5)
x, y, z
N1–H1/O1
C12–H12/O1
C2–H2/O1
x, ꢁy + ½, z ꢁ ½
x, ꢁy + ½, z ꢁ ½
ꢁx + 1, y + ½, ꢁz + ½
ꢁx + 1, y + ½, ꢁz + ½
ꢁx + 2, y ꢁ ½, ꢁz + ½
x ꢁ 1, ꢁy + ½, z ꢁ ½
x ꢁ 1, ꢁy + ½, z ꢁ ½
ꢁx + 2, ꢁy, ꢁz
C3–H3/F1B
C10–H10/F3A
C4–H4/F2B
C4–H4/F1A
C11–H11/F1A
C14–F3A/Cg2
C14–F1B/Cg2
T-2-1 (Pna21, Z ¼ 4)
N1–H1/O1
C12–H12/O1
C5–H5/F2
C5–H5/F1
C11–H11/F5
C3–H3/F3
C2–H2/Cg2
C14–F2/Cg1
x, ꢁy + 3/2, z ꢁ ½
x, ꢁy + 3/2, z ꢁ½
0.89(2)
0.93(2)
1.01(3)
1.01(3)
0.97(2)
0.89(2)
0.98(2)
1.331(2)
2.822(2)
3.410(2)
3.805(3)
3.235(2)
3.453(2)
3.338(2)
3.686(3)
4.351(3)
1.98(2)
2.83(2)
2.85(3)
2.68(3)
2.69(2)
2.69(2)
2.92(2)
3.159(2)
156(2)
122(2)
159(2)
115(2)
136(2)
131(2)
136(2)
148.5(1)
x + ½, ꢁy + 3/2, z
x + ½, ꢁy + 3/2, z
x + ½, ꢁy + 3/2, z + 1
x + ½, ꢁy + 3/2, z + 1
ꢁx, ꢁy + 2, z ꢁ ½
ꢁx, ꢁy + 1, z + ½
x ꢁ ½, ꢁy + ½, z
ꢁx + ½, y ꢁ ½, z ꢁ ½
T-2-2 (P2
1
/c, Z ¼ 4)
C8–H8/O1
N1–H1/O1
C6–H6/F6
C4–H4/F4
C3–H3/F4
C12–H12/F5
0.95(2)
0.88(2)
0.97(2)
0.96(2)
0.91(2)
0.93(2)
2.942(2)
2.830(2)
3.346(2)
3.204(2)
3.249(3)
3.479(2)
2.41(2)
2.00(2)
2.59(2)
2.56(2)
2.67(2)
2.62(2)
115(1)
158(2)
135(2)
124(2)
122(2)
154(2)
x, y, z
x, ꢁy + ½, z + ½
x, ꢁy + ½, z ꢁ ½
ꢁx, y + ½, ꢁz + 3/2
ꢁx, y + ½, ꢁz + 3/2
ꢁx, y ꢁ ½, ꢁz + 3/2
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Table 2 (Contd.)
D—H/A
ꢀ
D–H/A
ꢀ
ꢀ
ꢀ
:D–H/A/
D/A/A
H/A/A
Symmetry
C8–H8/F1
C9–H9/F1
C3–H3/F2
0.95(2)
0.97(2)
0.91(2)
3.273(2)
3.385(2)
3.458(2)
2.60(2)
2.79(2)
2.67(2)
128(2)
120(2)
146(2)
ꢁx + 1, y + ½, ꢁz + ½
ꢁx + 1, y + ½, ꢁz + ½
x, y + 1, z
T-3-1 (P2
C8–H8/O1
N1–H1/O1
C9–H9/O1
C11–H11/F1B
C6–H6/F4
C12–H12/F3B
C5–H5/F4
1
/n, Z ¼ 4)
0.94(2)
0.89(1)
1.00(1)
0.97(2)
0.99(2)
0.95(1)
0.96(2)
0.91(2)
0.97(2)
0.91(1)
0.96(2)
2.874(2)
2.926(2)
3.543(2)
3.604(4)
3.738(2)
3.347(2)
3.522(2)
3.467(2)
3.609(2)
3.041(4)
3.455(3)
2.26(2)
2.07(1)
2.55(1)
2.78(2)
2.87(2)
2.66(1)
2.89(2)
2.85(1)
2.80(2)
2.38(2)
2.72(2)
122(1)
160(1)
172(1)
143(1)
147(1)
130(1)
125(1)
126(1)
141(1)
129(1)
134(1)
x, y, z
ꢁx + 3/2, y + ½, ꢁz + ½
ꢁx + 1, ꢁy, ꢁz
ꢁx + 3/2, y + ½, ꢁz ꢁ ½
ꢁx + 3/2, y ꢁ ½, ꢁz + ½
x + ½, ꢁy + ½, z + ½
x + ½, ꢁy + ½, z + ½
x + ½, ꢁy + ½, z + ½
x + ½, ꢁy + ½, z ꢁ ½
x, y, z + 1
C4–H4/F4
C11–H11/F6
C4–H4/F3A
C3–H3/F2B
T-3-2 (Pccn, Z ¼ 8)
C8–H8/O1
N1–H1/O1
C12–H12/O1
C6–H6/F4A
C4–H4/F2
x, y, z + 1
0.96(2)
0.91(2)
0.93(2)
0.95(2)
0.99(2)
0.99(2)
2.908(2)
2.846(2)
3.449(3)
3.648(3)
3.335(3)
3.667(3)
2.39(2)
1.97(2)
2.88(2)
2.71(2)
2.76(2)
2.79(2)
114(2)
162(2)
121(2)
173(2)
118(2)
148(2)
x, y, z
ꢁx + 3/2, y, z + ½
ꢁx + 3/2, y, z + ½
ꢁx + 3/2, ꢁy ꢁ ½, z
x + ½, y ꢁ ½, ꢁz
x + ½, ꢁy, ꢁz + ½
C4–H4/F3
T-3-3 (P2
C8–H8/O1
1
/n, Z ¼ 4)
0.89(3)
0.90(4)
0.96(3)
1.01(3)
0.98(3)
0.95(3)
1.01(3)
1.00(3)
0.96(3)
0.91(3)
0.89(3)
1.335(4)
2.878(4)
3.019(3)
3.475(4)
3.442(3)
3.282(4)
3.460(7)
3.735(9)
3.704(4)
3.724(9)
3.626(3)
3.606(3)
4.320(3)
2.44(3)
2.29(4)
2.81(3)
2.80(3)
2.54(3)
2.77(3)
2.75(3)
2.88(3)
2.78(3)
2.93(3)
2.95(3)
3.303(2)
111(2)
138(3)
128(2)
122(2)
132(2)
130(2)
165(2)
140(2)
168(2)
135(2)
132(2)
132.7(2)
x, y, z
x + 1, y, z
x + 1, y, z
x + 1, y, z
N1–H1/O1
C6–H6/O1
C12–H12/O1
C3–H3/F2
C2–H2/F4B
C12–H12/F4A
C11–H11/F3
C9–H9/F4B
C5–H5/Cg2
C8–H8/Cg1
C14–F1/Cg1
x ꢁ ½, ꢁy ꢁ ½, z + ½
ꢁx + ½, y ꢁ ½, ꢁz + ½
ꢁx + 3/2, y ꢁ ½, ꢁz + ½
ꢁx + 1, ꢁy ꢁ 1, ꢁz
ꢁx, ꢁy, ꢁz
ꢁx, 1 ꢁ y, 1 ꢁ z
1 ꢁ x, 1 ꢁ y, 1 ꢁ z
½ + x, ½ ꢁ y, ½ + z
Table 3 List of intermolecular non-hydrogen contacts in the crystal lattice
ꢀ
ꢀ
ꢀ
:C–Y/X/
C–X/Y–C
X/Y/A
:C–X/Y/
Symmetry code
T-0-3
C14-F2/F2-C14
C14-F2/F3-C14
C14-F3/O1-C13
C15-F6/F1-C14
C15-F6/F2-C14
C14-F2/F3-C15
C14-F3/F5-C15
C14-F2/F4-C15
C15-F5/F6-C15
C15-F6/F3A-C14
C15-F4/F1A-C14
C15-F5/F1A-C14
C15-F6/F1B-C14
C14-F3/F6A-C15
C14-F3/F4A-C15
C14-F1/F5A-C15
C14-F1/F4B-C15
3.125(3)
2.966(3)
3.073(2)
2.986(3)
3.136(3)
3.073(2)
3.045(2)
3.123(3)
3.040(3)
3.090(4)
2.929(8)
2.813(6)
3.122(5)
2.908(3)
3.061(6)
3.068(9)
2.994(9)
170.0(1)
118.0(1)
128.5(1)
115(1)
143.7(2)
107.2(1)
111.4(1)
171.5(1)
103.8(1)
117.4(2)
99.7(1)
105.7(1)
175.6(1)
136.2(2)
125.2(2)
131.5(2)
100.7(2)
170.1(1)
115.1(1)
145.0(1)
113.0(1)
99.3(1)
149.7(1)
119.7(1)
123.2(1)
134.2(1)
140.4(2)
150.7(5)
157.9(3)
120.4(3)
142.2(2)
119.1(4)
161.5(6)
152.7(6)
ꢁx, 2 ꢁ y, ꢁz
1 ꢁ x, 2 ꢁ y, ꢁz
y, ꢁx, ꢁ¼ + z
T-1-0
T-2-1
x, y, 1 + z
ꢁ½ + x, ½ ꢁ y, 1 + z
x, 3/2 ꢁ y, ꢁ½ + z
ꢁx, ½ + y, ½ ꢁ z
ꢁx, 1 ꢁ y, ꢁz
T-2-2
ꢁx, ꢁy, 1 ꢁ z
T-3-1
½ + x, ½ ꢁ y, ½ + z
1 ꢁ x, 1 ꢁ y, ꢁz
1 ꢁ x, 1 ꢁ y, ꢁz
1 ꢁ x, ꢁy, ꢁz
T-3-2
T-3-3
½ + x, 1 ꢁ y, ½ ꢁ z
½ + x, ½ ꢁ y, ½ + z
1 ꢁ x, 1 ꢁ y, 1 ꢁ z
ꢁx, 1 ꢁ y, 1 ꢁ z
ꢀ
ꢀ
[
163(2) ] C–H/F intermolecular H-bonds which provide
[d ¼ 3.073 A], involving F3 and O1 in the crystal, pointing to
additional stability to the crystal packing. High resolution
X-ray data for electron density measurements have been
collected on the crystal of this compound to evaluate the
topological characteristics associated with this well-defined C–
H/F–C H-bond and will be reported separately. It is further
interesting to observe the presence of a C–F/O]C contact
the relevance and extreme significance of sigma-hole bonding
41
in fluorine containing compounds.
Thus such halogen
bonding features point to the possibility of polarization of the
42
electron density on the fluorine atom which otherwise is
considered non-polarisable and is currently an active topic of
43
debate and consideration.
1
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Table 4 A comparison of lattice parameters and dihedral angles of the present compounds with fluorinated benzanilides (crystal structures investigated
for both series)
Sample code
Sp.Gr./Z
Lattice parameters
T-0-1
P2 /c, 8
1
9.991, 16.42, 15.64, 90, 108.5, 90
5.42, 6.26, 15.53, 90, 97.45, 90
5.36, 7.71, 14.24, 77.0, 81.6, 89.6
5.34, 7.60, 12.94, 92.12, 100.18, 90.16
21.21, 6.78, 9.72, 90, 100.9, 90
5.19, 5.88, 35.13, 90, 90, 90
2
-Fluoro-N-phenylbenzamide (DC1)
T-0-3
-Fluoro-N-phenyl benzamide (DC3)
T-1-1
-Fluoro-N-(2-fluorophenyl)benzamide (DC7)
P2 , 2
1
ꢁ
P1, 2
ꢁ
P1, 2
C2/c, 4
4
2
T-2-0
N-(3-Fluorophenyl)benzamide (DC5)
T-2-1
2-Fluoro-N-(3-fluorophenyl)benzamide (DC10)
T-2-2
P2
P2
1
/c, 4
/c, 4
13.85, 8.61, 10.10, 90, 100.13, 90
8.069, 5.39, 23.23, 90, 90.20, 90
9.03, 13.74, 11.37, 90, 90, 90
1
Pna2
Pca2
P2
C2/c, 4
1
, 4
1
, 4
8.24, 5.20, 24.66, 90, 90, 90
1
/c, 4
12.06, 12.54, 8.88, 90, 91.8, 90
25.24, 5.38, 8.20, 90, 108.14, 90
5.06, 5.35, 19.302, 90, 95.51, 90
5.20, 14.39, 18.18, 90, 97.4, 90
5.46, 7.69, 13.04, 106.75, 100.37, 90.02
3
-Fluoro-N-(3-fluorophenyl)benzamide [DC11(plate)]
-Fluoro-N-(3-fluorophenyl)benzamide [DC11(needle)]
3
T-3-3
P2 , 2
1
1
P2 /n, 4
ꢁ
P1, 2
4-Fluoro-N-(4-fluorophenyl)benzamide (DC15)
ꢀ
Table 5 Selected torsion angles in degree ( )
Compound code
C2–C1–C13–N1
C1–C13–N1–C7
177.2(3), 178.1(3)
171.72, 179.76
C13–N1–C7–C12
b
b
b
T-0-1
T-0-1
120.1(3), 121.5(3)
132.64, 121.68
162.5(3), 118.4(4)
168.14, 163.59
a
b
b
b
T-0-3
T-0-3
148.93(12)
155.52
179.38(11)
179.27
152.58(13)
176.05
a
T-1-0
T-1-0
157.73(12)
157.16
175.30(12)
173.75
119.53(15)
168.21
a
T-1-1
T-1-1
123.45(13)
—
173.59(12)
—
128.85(11)
—
ac
T-2-0
T-2-0
150.77(15)
150.75
177.01(15)
177.01
165.21(16)
165.20
a
T-2-1
T-2-1
110.73(15)
126.27
177.19(12)
178.22
127.58(14)
176.32
a
T-2-2
T-2-2
151.09(16)
157.03
174.88(15)
178.96
154.98(17)
175.88
a
T-3-1
T-3-1
119.87(19)
129.37
177.31(16)
177.74
173.54(17)
175.50
a
T-3-2
T-3-2
147.9(3)
156.60
172.5(3)
178.81
155.8(3)
176.59
a
T-3-3
T-3-3
146.1(3)
155.53
175.9(3)
179.10
147.3(3)
176.18
a
a
b
c
Value obtained from theoretical B3LYP/6-31G** calculation. Indicates another molecule in an asymmetric unit. The structure contains half
a molecule in an asymmetric unit which is disordered and hence theoretical calculations could not be performed.
3
4
Structure of T-1-1
C(sp ) hydrogen bond (involving the most acidic hydrogen H2
with F1A (of major occupancy)] links the molecular chain, thus
providing further stabilization to the crystal [Fig. 4(c)]. Among
Compound T-1-1 crystallizes in the monoclinic space group C2/c
0
0
with Z ¼ 4 (Z ¼ 0.5). The Z ¼ 0.5 in the molecule having no
symmetry [Fig. 4(a)] suggests the presence of static disorder
around the amide bond which generates the second half of the
molecule around the centre of inversion as is depicted in
2
3
all C(sp )–H/F–C(sp ) hydrogen bonds, one involving H2 with
F1A propagates through the 2 screw along the crystallographic
1
b-axis and the other involving H3 with F2A utilizes the c glide-
plane.
3
Fig. 4(b). The CF group in the molecule also has two fold
rotational disorder with occupancies 0.64(3) (labeled as F1A,
F2A, and F3A) and 0.36(3) (labeled as F1B, F2B, and F3B).
Packing in the crystal structure involves a strong N–H/O]C
hydrogen bond utilizing the local 2-fold symmetry which trans-
lates along the crystallographic c-axis, thus forming a molecular
chain along that direction [Fig. 4(c)]. The molecular chain is
5
Structure of T-2-0
The molecule crystallizes in the centrosymmetric monoclinic
space group P2 /c with Z ¼ 4 having an intra-molecular C8-
1
H8/O1 hydrogen bond [Fig. 5(a)] which stabilizes the molecular
3
further stabilized by C–H/O]C (involving H4) and C(sp )–F/
p (involving F2B) with electron deficient phenyl ring by utiliza-
3
conformation. The CF group in the molecule has a two fold
rotational disorder with occupancies 0.57(3) (labeled as F1A,
F2A, and F3A) and 0.43(3) (labeled as F1B, F2B, and F3B). The
2
tion of the c glide-plane [Fig. 4(c)]. The weak C(sp )–H/F–
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Fig. 2 (a) ORTEP of T-0-3 drawn with 50% ellipsoidal probability. The
2
dotted line indicates an intra-molecular C(sp )–H/O]C H-bond. (b)
Packing view of T-0-3, showing strong N–H/O]C hydrogen bonds,
weak C–H/O]C hydrogen bonds along with F/ F interactions. (c)
Packing diagram of T-0-3. View down the bc plane, showing weak
2
3
2
C(sp )–H/F–C(sp ) and C(sp )–H/p interactions.
molecules are packed with the involvement of strong N–H/O]
C hydrogen bonds, generating a molecular chain [Fig. 5(b)] along
the c-axis, further stabilized by additional C–H/O]C H-
3
bonding (involving H12) and C(sp )–F/p weak intermolecular
interactions (involving the disordered fluorine atoms F3A and
F1B) with electron deficient phenyl ring, by utilization of the c
glide-plane in the molecular packing [Fig. 5(b)]. The molecular
2
3
chains are connected by a weak bifurcated C(sp )–H/F–C(sp )
involving H4 with F1A and F2B) H-bond propagating along the
(
Fig. 1 (a) ORTEP of T-0-1 drawn with 50% ellipsoidal probability. The
dotted line indicates an intra-molecular hydrogen bond. (b) Packing view
down the ac plane in T-0-1. Showing N–H/O]C and C–H/O]C
hydrogen bonds propagating along the a-axis leading to formation of
crystallographic c-axis. The packing in the crystal structure also
involves formation of zigzag chains via C–H/O]C (involving
2
3
H2) along with C(sp )–H/F–C(sp ) H-bonds (involving H3 and
the most acidic hydrogen H10 with F3A and F1B) utilizing the 2
screw-axis of symmetry along the b-axis [Fig. 5(c)]. Molecular
2
3
a /ABAB/ molecular chain. (c) Network of C(sp )–H/F–C(sp ) weak
hydrogen bonds along with C–H/p interaction down the bc plane
forming a sheet-like structure in T-0-1.
1
2
3
dimers [Fig. 5(d)] formed by a C(sp )–H/F–C(sp ) H-bond
1
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Fig. 4 (a) ORTEP of an asymmetric unit, depicting a half molecule of T-
1
-1 drawn with 50% ellipsoidal probability. The major component of the
disordered CF group (of higher occupancy) has been shown for the sake
3
of clarity. (b) T-1-1, containing a full molecule generated using a center of
symmetry. The true molecule contains two trifluoromethyl groups in the
ortho position, both of which are disordered. (c) Packing view down the
2
2
ac plane depicts involvement of N–H/O]C, C(sp )–H/O]C, C(sp )–
3
3
H/F–C(sp ) and C(sp )–F/p interactions in packing of T-1-1.
(
involving H11 with F1A) augment the crystal packing, thus
Fig. 3 (a) ORTEP of T-1-0 drawn with 50% ellipsoidal probability. (b) Helix
providing additional stability to the molecular assembly.
2
3
formation by N–H/O]C, C(sp )–H/O]CandC(sp )–F/O]C through
the 4 screw along the c-axis in T-1-0. (c) Packing view down the ac plane in T-
-0, depicting C–H/p interactions along with N–H/O]C, and C(sp )–
H/O]C. (d): Two helixes along the c-axis formed by N–H/O]C and
1
6
Structure of T-2-1
2
1
The molecule [Fig. 6(a)] crystallizes in the non-centrosymmetric
orthorhombic space group Pna2
with Z ¼ 4. Strong N–H/O
2
2
3
C(sp )–H/O]C held with weak C(sp )–H/F–C(sp ) interactions in T-1-0.
1
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2
hydrogen bonds along with C(sp )–H/O]C and C–H/p
interactions (involving H2) form molecular chains along the
2
a-axis [Fig. 6(b)]. The chain is linked by the weak C(sp )–H/F–
3
C(sp ) hydrogen bond (involving fluorine atoms F3 and F5 with
H3 and H11 respectively) propagating along the crystallographic
c-axis utilizing the 2
1
screw-axis of symmetry [Fig. 6(b)]. It is of
interest to note that the most acidic hydrogen atom H5 is
2
3
involved in the formation of bifurcated C(sp )–H/F–C(sp )
hydrogen bonds (with fluorine atoms F1 and F2) linking two
molecular chains formed by a strong N–H/O]C H-bond
propagating in the direction of the a-axis [Fig. 6(c)]. It is also of
3
interest to note that the C(sp )–F/p interactions (involving F2
ꢀ
with electron deficient phenyl ring, d ¼ 3.159A) utilize the n-glide
in crystal packing [Fig. 6(d)], thus providing stabilization to the
3
crystal packing. Finally, short intermolecular C(sp )–F/F–
3
C(sp ) interactions (involving F6 with F1 and F2) reveal the
presence of lipophilic regions, wherein the trifluoromethylated
moieties face each other in the crystal, and hence are involved in
such interactions which provide additional stability to the crystal
packing (the fluorous effect). These characteristic supramolec-
ular features have also been observed in the cyclo-addition
19
reactions of –CF substituted tetrathiafulvalene derivatives.
3
7
Structure of T-2-2
The molecule crystallizes in the centrosymmetric monoclinic
space group P2 /c with Z ¼ 4, with a characteristic intra-
1
molecular C–H/O]C hydrogen bond [Fig. 7(a)]. In addition to
a N–H/O]C hydrogen bonded chain along the c-axis, a weak
2
3
C(sp )–H/F–C(sp ) hydrogen bond, involving the most acidic
hydrogen atom H6 with F6 [Fig. 7(b)] along with p/p stacking
ꢀ
3.674(2)A) [Fig. 7(c)] stabilizes the crystal structure. The
(
formation of a layer motif on the ac-plane is achieved with
2
3
C(sp )–H/F–C(sp ) hydrogen bonds, involving the relatively
less acidic hydrogen atoms H12 with F5, H8 with F1, H4 and H3
with bifurcated acceptor F4, and bifurcated donor H3 with F4
and F2 [Fig. 7(d)], all along the crystallographic b-axis utilizing
3
the 2 screw axis of symmetry (Table 2). Weak C(sp )–F/F–
1
3
C(sp ) contacts involving F5 and F3 form a chain along the
b-axis [Fig. 7(e)] while the F3/F2 contact forms a chain along
the c-axis [Fig. 7(f)]. Weak F2/F4 contacts form dimeric motifs
which are further connected by dimeric F6/F5 contacts gener-
ating a staircase motif in the crystal [Fig. 7(g) and Table 3].
8
Structure of T-3-1
The structure depicts the monoclinic space group P2
1
/n with Z ¼
4
and the presence of a typical intra-molecular C–H/O]C
3
hydrogen bond [Fig. 8(a)]. One of the CF groups at C14 is found
to be two fold rotationally disordered with occupancies 0.426(5)
labeled as F1A, F2A, and F3A) and 0.574(5) (labeled as F1B,
F2B, and F3B). The other CF group is ordered (consisting of
(
3
F4, F5 and F6). The packing in the crystal involves formation of
chains along the b-axis by a strong N–H/O hydrogen bond and
a weak C(sp )–H/F–C(sp ) H-bond (involving the most acidic
Fig. 5 (a) ORTEP of T-2-0 drawn with 50% ellipsoidal probability. The
2
3
dotted line indicates an intramolecular hydrogen bond. Only the major
3
component of the disordered CF group (of higher occupancy) has been
shown for the sake of clarity. (b) Packing view down the ac plane depicts
3
2
2
formation of a zigzag chain with C(sp )–H/O]C and weak C(sp )–H/
2
2
propagation of N–H/O]C, C(sp )–H/O]C, C(sp )–H/F–C(sp ) H-
3
2
F–C(sp ) H-bonds in T-2-0. (d) Dimer motif formation by C(sp )–H/F–
C(sp ) in T-2-0 in addition to N–H/O and C–H/O]C H-bonds.
3
bonds and C(sp )–F/p interactions along the c-axis in T-2-0. (c) The
3
1
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hydrogen atoms H11 and F1B, H3 and F2B, H6 and F4, and
2
H12 and F3B) [Fig. 8(b) and (c)]. Furthermore, the C(sp )–H/
3
F–C(sp ) H-bond involving H11 with F6, and bifurcated H4, H5
with F4 also stabilizes the crystal structure with the utilization of
3
2
the n-glide-plane [Fig. 8(c)]. The C(sp )–H/F–C(sp ) chains are
2
3
further stabilized by additional C(sp )–H/F–C(sp ) interactions
involving H4 with F3A and H3 with F2B) forming chains along
(
the c-axis [Fig. 8(c)]. C–H/O]C hydrogen bonds (involving H9
with O1) generate molecular dimeric motifs, and two such
3
3
consecutive motifs are stabilized via weak C(sp )–F/F–C(sp )
contacts in the crystal lattice [Fig. 8(d)].
9
Structure of T-3-2
The molecule crystallizes in the centrosymmetric orthorhombic
space group Pccn with Z ¼ 8. Fig. 9(a) represents the molecular
conformation along with a C–H/O intramolecular hydrogen
bond involving H8 and O1. One of the trifluoromethyl groups
(
connected to C5) displays two-fold rotational disorder, the
major and minor occupancies being 0.889(4) (for F4A, F5A, and
F6A) and 0.111(4) (for F4B, F5B, and F6B) respectively. The
fluorine atoms having minor occupancy have only been refined
with isotropic displacement parameters and these atoms were not
considered to take part in intermolecular interactions. The
crystal packing of the compound involves a well defined N–H/
O]C and C–H/O]C (involving H12) hydrogen bond which
steers the molecule to pack along the c-axis with additional
ꢀ
stabilization from p/p stacking [3.836(2)A] [Fig. 9(b)]. It is of
interest to note that the acidic hydrogens (H4 and H6) are
2
3
involved in formation of C(sp )–H/F–C(sp ) hydrogen bonds.
The hydrogen atom H4 as a donor is involved in formation of
bifurcated hydrogen bonds with F2 and F3 as acceptors, the
former forming chains along the [110] direction utilizing the
n-glide plane and the latter forming chains along the a-axis
1
utilizing the 2 screw axis of symmetry [Fig. 9(c) and (d)]. The
other hydrogen atom, namely H6, forms highly directional
ꢀ
interactions [173(2) ] along the crystallographic c-axis with F4A.
3
3
In addition, weak C(sp )–F/F–C(sp ) interactions, involving F3
with F6A, pack the molecules (Table 1) along the crystallo-
graphic a-axis [Fig. 9(d)].
1
0 Structure of T-3-3
The molecule crystallizes in the centrosymmetric monoclinic
space group P2
/n with Z ¼ 4, with an intra-molecular C–H/
O]C hydrogen bond, involving H8, present in the molecule
Fig. 10(a)]. The CF group at C15 exhibits a two fold disorder
with occupancies 0.47(1) (labeled as F4A, F5A, and F6A),
.53(1) (labeled as F4B, F5B, and F6B). The well defined N–H/
1
[
3
0
O]C and C–H/O]C hydrogen bonds (involving H6 and H12)
steer the molecules to pack along the a-axis [Fig. 10(b)]. It is
again noteworthy that the most acidic hydrogens, namely H3,
H5, H9 and H11 (adjacent to different electron withdrawing
trifluoromethyl groups), are involved in the formation of
Fig. 6 (a) ORTEP of T-2-1 drawn with 50% ellipsoidal probability. (b)
2
Packing view down the ab plane, depicting N–H/O]C, C(sp )–H/O]
2
3
different intermolecular interactions. The C(sp )–H/F–C(sp )
2
3
2
C, C(sp )–H/F–C(sp ), and C(sp )–H/p intermolecular interactions in
3
3
T-2-1. (c) Packing view down the ac plane, depicting C(sp )F/F–C(sp )
2
3
and (sp )–H/F–C(sp ) intermolecular contacts along with N–H/O]C
This journal is ª The Royal Society of Chemistry 2012
2
and C(sp )–H/O]C propagating along the crystallographic b-axis in T-
2
3
-1. (d) Packing view of T-2-1 showing C(sp )–F/p interaction.
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Fig. 7 (a) ORTEP of T-2-2 drawn with 50% ellipsoidal probability. The dotted line indicates an intra-molecular hydrogen bond. (b) Packing view down
2
3
the ac plane, showing N–H/O]C hydrogen bonding along with weak C(sp )–H/F–C(sp ) H-bonds in T-2-2. (c) Packing view down the ac plane
showing p/p interactions along with strong N–H/O]C hydrogen bonds in T-2-2. (d) Packing diagram of T-2-2, showing formation of a sheet-like
2
3
3
structure by weak C(sp )–H/F–C(sp ) interactions on the ac plane. Other non-participating fluorine atoms are omitted for clarity in T-2-2. (e) C(sp )–
3
3
3
F/F–C(sp ) contacts forming molecular chains along the b-axis in T-2-2. (f) Formation of chains down the bc plane by C(sp )–F/F C(sp ) contacts in
T-2-2. (g) Dimers formed by C(sp )–F/F–C(sp ) contacts in T-2-2 forming a molecular staircase.
3
3
H-bond (involving H9 with disordered fluorine F4B, H11 with
3
n-glide), H12 with F4A and H2 with F4B (utilizing the 2 screw
1
3
3
3
F3), along with C(sp )–F/F–C(sp ) (involving F1 with F5A and
F4B), forms a dimer motif [Fig. 10(c)], which further packs as
axis of symmetry)] and C(sp )–F/F–C(sp ) [involving F3 with
F4A], utilizing the n-glide plane of symmetry [Fig. 10(c) and
Table 2]. The C–H/p interactions involving H8 and H5 are also
involved in the formation of a molecular dimeric motif
2
a herringbone arrangement by the utilization of other C(sp )–
3
H/F–C(sp ) interactions [involving H3 with F2 (utilizing the
1
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Fig. 10(d)]. C(sp )–F/p (involving F1 and Cg1) interaction
with the electron deficient phenyl ring generates a molecular
3
[
chain with utilization of the n-glide [Fig. 10(d) and Table 2].
Discussion
The analysis of the above-mentioned crystal structures brings out
some interesting results in terms of variations in molecular
conformations and crystal packing which accompany the
replacement of a hydrogen atom in benzanilide with a tri-
fluoromethyl group. It is of interest to compare the supramo-
lecular features in these compounds with the already well-
investigated fluorinated benzanilides [Table 4] to realize the
importance and contribution of weak intermolecular interactions
3
2
involving the C(sp )–F bond with C(sp )–F bond. It is imperative
that relatively strong hydrogen bonds N–H/O]C control the
pre-organization of molecules in the crystal structure of tri-
fluoromethylated benzanilides. Packing in the crystal structure
along another two directions involves the presence of weak
H-bonds of the type C–H/O, C–H/F, and C–H/p and
interactions like C–F/F–C, C–F/ p and p/ p stacking which
provide additional stability to the crystal packing. It is of interest
to note that in the structures of DC3 [IUPAC name: 4-fluoro-N-
phenyl benzamide: the nomenclature for related compounds in
3
this series is defined in Table 4] and T-0-3, –F and –CF in the
para position of the phenyl ring on the benzoyl side is nearly
isostructural as is reflected in the values for the lattice parameters
and space group [Table 4]. The two crystal structures also exhibit
a similarity in the nature of the intermolecular H-bonds and
interactions which govern the crystal packing. This feature is
illustrated in Fig. 11 and a comparison with Fig. 2(c) depicts the
above-mentioned feature related to packing of molecules in the
two crystalline solids. Furthermore, it is also to be noted that
the presence of the aryl C–F group in DC1 [2-fluoro-N-phenyl-
benzamide] results in monoclinic non-centrosymmetric space
group P2
1
whereas the presence of the –CF
3
group in T-0-1
/c packing
results in the centrosymmetric space group P2
1
2
3
wherein weak C(sp )–H/F–C(sp ) intermolecular interactions
pack the molecules along the crystallographic c-axis, thereby
generating the inversion center in the crystal lattice [Table 4]. T-
2
-0 (–CF
3
in the meta position on the aniline side) and DC5 [N-
(
3-fluorophenyl)benzamide] have a completely different crystal
packing although these crystallize in the same space group with
the same number of molecules in the unit cell [Fig. 12]. This
results from the initial molecular-recognition events wherein the
N–H/O]C hydrogen bonds assemble the molecules utilizing
different symmetry elements, the subsequent stabilization
2
3
coming from weak C(sp )–H/F–C(sp ) intermolecular H-
bonds. T-2-1 and DC10 exhibit similar features as in the previous
case (T-2-0 and DC5) wherein the two molecules crystallize in
equivalent space groups, yet the supramolecular packing is
2
3
different [Fig. 13]. The importance of weak C(sp )–H/F–C(sp )
H-bonds is realized in the packing motifs of all the molecules in
this study wherein these interactions utilize the symmetry
Fig. 8 (a) ORTEP of T-3-1 drawn with 50% ellipsoidal probability. The
dotted line indicates an intra-molecular hydrogen bond. Only the major
3
component of the disordered CF group (of higher occupancy) has been
shown for the sake of clarity. (b) Packing view down the bc plane,
2
2
3
via C(sp )–H/F–C(sp ) H-bonds in T-3-1. (d) Dimeric motifs via the C–
depicting a strong N–H/O]C hydrogen bond with C(sp )–H/F–
3
3
H/O]C H-bond along with C(sp )–F/F–C(sp ) intermolecular
contacts in T-3-1.
3
C(sp ) propagating along the b-axis in T-3-1. (c) The formation of sheets
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elements of the space group efficiently in generating the crystal-
line environment. It is an important observation that the length
2
3
and directionality features associated with C(sp )–H/F–C(sp )
intermolecular interactions in these solids exhibit improved H-
bonding characteristics compared to those observed in fluori-
nated benzanilides. This is reflected in shorter H/F distances
ꢀ
ꢀ
and also the C–H/F angles which vary between 120 and 168 ,
depicting directionality of the hydrogen atom towards the fluo-
rine lone pairs of electrons, thereby signifying greater availability
of the electron density on these fluorine atoms. This observation
3
renders support to the statement that ‘‘/C(sp )–F fluorine is
2
44
a better hydrogen bond acceptor than C(sp )–F’’. The strong
electron withdrawing nature of CF3 enhances the acidity of
neighboring hydrogen atoms leading to an increase in the
number of hydrogen atoms which participate in hydrogen
bonding, compared to that observed in the case of fluorinated
benzanilides. Thus, in addition to the formation of conventional
N–H/O]C and C–H/O]C hydrogen bonds, the enhanced
acidity increases the propensity of formation of hydrogen bonds
2
3
involving weak but directional C(sp )–H/F–C(sp ) intermolec-
ular interactions, which stabilizes the crystal structure and leads
to formation of different packing arrangements in the crystal.
The availability of greater electron density also manifests itself in
the formation of packing motifs generated via the lone-pair/p
interaction between F and phenyl ring, as is observed in the case
of T-0-1, T-1-1, T-2-0, T-2-1 and T-3-3. It is interesting to note
that four mono-trifluoromethylated benzanilides [T-0-1, T-0-3,
T-1-0, T-2-0] have considerable variations in the symmetry of the
crystal system (with concomitant variations in crystal packing),
ꢁ
starting from the least symmetric triclinic centrosymmetric P1
for T-0-3 to noncentrosymmetric P4
tions are observed for the six di-trifluoromethylated benzanilides
T-1-1, T-2-1, T-2-2, T-3-1, T-3-2, and T-3-3] wherein the space
1
for T-1-0. Similar varia-
[
group varies from monoclinic centrosymmetric P2 /c in T-2-2, to
1
orthorhombic non-centrosymmetric Pna2 for T-2-1 and finally
1
in orthorhombic centrosymmetric Pccn for T-3-2. It is also of
interest to note variations in crystal density which exist between
isomeric mono- and bis-trifluoromethylated benzanilides, the
ꢁ3
crystal density varying from 1.419 gm cm in T-1-0 to 1.552 gm
ꢁ3
cm in T-0-3 in the former and from 1.567 in T-3-2 to 1.648 gm
ꢁ3
cm in T-2-2 (closer value of 1.640 in T-3-3).
The analysis of molecular conformation [Table 5] shows
significant deviation of three planes from planarity. The torsion
angle for the central amide bond, C1–C13–N1–C7, remains
invariant for both the experimental and theoretical values. The
presence of a trifluoromethyl group in the ortho position on the
benzoyl side of the aryl ring leads to increased rotation around
the C–C single bonds with respect to the central amide group,
resulting in significant deviation from planarity [observed in T-0-
ꢀ
1
, T-2-1 and T-3-1, the torsion angles varying between 110 and
ꢀ
1
20 ]. This is because of the stereoelectronic effects which exist
3
between the carbonyl and CF groups (when these are in close
Fig. 9 (a) ORTEP of T-3-2 drawn with 50% ellipsoidal probability. The
proximity) and rotation around the C–C single bonds decreases
both the electrostatic repulsions and the steric effects which exists
between such groups. This distortion is considerably reduced
when the trifluoromethyl groups are present in meta and para
positions (as observed in T-0-3, T-2-0, T-2-2, T-3-2 and T-3-3,
dotted line indicates an intra-molecular hydrogen bond. Only the major
3
component of the disordered CF group (of higher occupancy) has been
shown for the sake of clarity. (b) Packing diagram involving N–H/O]C
and C–H/O]C H-bonds along with p/p interactions viewed down the
2
3
ac plane in T-3-2. (c) Weak C(sp )–H/F–C(sp ) interactions in T-3-2 [there
exists no center of symmetry in the C–H/F motif]. (d) Intermolecular
ꢀ
the experimental torsion angle varying between 146 and 151 on
ꢀ
2
3
3
3
C(sp )–H/F–C(sp ) and C(sp )–F/F–C(sp ) interactions in T-3-2.
the benzoyl side and 147–165 on the aniline side). Thus the
1
986 | CrystEngComm, 2012, 14, 1972–1989
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Fig. 11 Packing view down the bc plane in DC3 connected via weak
intermolecular C–H/p H-bonds.
Fig. 12 Packing view down the ac plane in T-2-0 and DC5 depicting the
orientation of the molecules in different layers in the solid state connected
via a network of strong and weak intermolecular H-bonds.
3
change in the position of the CF group leads to systematic
variations in the molecular conformation. This is further
supported by the presence of an intra-molecular C–H/O]C H-
bond which stabilizes the molecular conformation in the above-
mentioned compounds as well. In addition the molecular
conformation of T-0-1 and T-3-1 is also stabilized by an intra-
molecular C–H/O]C H-bond because the C–H bond from the
aniline side of the benzanilide ring has the desired planarity to
form the desired H-bond with the C]O [the experimental C13–
ꢀ ꢀ
Fig. 10 (a) ORTEP of T-3-3 drawn with 50% ellipsoidal probability.
The dotted line indicates an intramolecular hydrogen bond. Only fluorine
atoms of higher occupancy have been shown for the sake of clarity. (b)
Packing view down the ab plane, depicting a strong N–H/O]C bond
along with a C–H/O]C hydrogen bond in T-3-3. (c) Packing view
N1–C7–C12 torsion angle being 162.5 and 173.5 for T-0-1 and
3
3
3
H/F–C(sp ) H-bonds and C(sp )–F/F–C(sp ) interactions in T-3-3. (d)
3
Packing view depicting C–H/p and C(sp )–F/p intermolecular inter-
actions down the bc plane in T-3-3.
2
down the bc plane displays formation of a herringbone sheet by C(sp )–
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deficient, also provides directionality and stabilization to the
crystal structure. These studies bring out the versatility associ-
ated with weak H-bonds involving organic fluorine. From
hybridization considerations, these are expected to be stronger
2
2
than the initially investigated C(sp )–H/F–C(sp ) interactions
in mono- and di-fluorinated benzanilides due to the greater
availability of the lone pairs on the fluorine atom. It is also
noteworthy that non-covalent C–F/F–C intermolecular
contacts wherein the trifluoromethylated groups come close to
each other, provide stabilization, establishing the importance of
the ‘‘fluorous effect’’ in organic compounds containing organic
fluorine. It is now of interest to extend such studies to mixed-
2
3
fluorinated systems containing both C–F(sp ) and C–F(sp )
bonds in the same molecule and evaluate the nature of inter-
molecular interactions present in these compounds.
Acknowledgements
PP thanks IISER Bhopal for research and instrument facilities,
UGC for JRF-SRF funding and Mr Raveesh, Mr Amol
Dikundwar and Dr Susanta Kumar Nayak for training and data
collection. The authors thank Prof T. N. Guru Row for data
collection on the CCD facility at IISc, Bangalore under the
IRHPA-DST Scheme and Dr V. Srinivasan for performing the
theoretical calculations. DC thanks the DST-Fast track scheme
2010 for funding.
Fig. 13 View down the ac plane in T-2-1 [connected via weak C–
2
3
2
H(sp )/F–C(sp ) H-bonds] and DC10 [connected via weak C–H(sp )/
2
F–C(sp ) H-bonds].
T-3-1 respectively]. It is of interest to note that in T-1-0 (CF3
group on the aniline side of the benzanilide molecule), the
ꢀ
experimental C13–N1–C7–C12 torsion angle is 119.5 , indicating
deviation from planarity. This is to minimize the dipole–dipole
repulsions which exist between the N–H bond and the net-dipole
References
3
moment from the –CF group. The overall differences which
1
2
D. Philp and J. F. Stoddart, Angew. Chem., Int. Ed., 1996, 35, 1154.
G. R. Desiraju and T. Steiner, The Weak Hydrogen Bond in Structural
Chemistry and Biology, Oxford University Press, Oxford, 1999.
G. R. Desiraju, Angew. Chem., Int. Ed., 2011, 50, 52.
G. A. Jeffrey, Crystallogr. Rev., 2003, 9, 135.
(a) T. Steiner, Chem. Commun., 1997, 727; (b) G. R. Desiraju, Chem.
Commun., 2005, 2995; (c) E. Bosch, Cryst. Growth Des., 2010, 10,
exist between the conformations observed experimentally and
theoretically, with respect to deviations of the two aryl rings from
planarity, point out the significance of intermolecular interac-
tions and their directing roles to facilitate the packing of mole-
cules in the crystal.
3
4
5
3
808.
6
7
S. K. Nayak, M. K. Reddy, T. N. Guru Row and D. Chopra, Cryst.
Growth Des., 2011, 11, 1578.
J. D. Dunitz, ChemBioChem, 2004, 5, 614.
Conclusions
The synthesis and characterization of a library of small molecules
containing the trifluoromethylated functional group in a series of
isomeric benzanilides bring out the relevance of non-covalent
8 (a) J. L. Alonso, S. Antolınez, S. Blanco, A. Lesarri, J. C. Lopez and
W. Caminati, J. Am. Chem. Soc., 2004, 126, 3244; (b) D. Chopra,
T. S. Cameron, J. D. Ferrara and T. N. Guru Row, J. Phys. Chem.
A, 2006, 110, 10465; (c) E. D’Oria and J. J. Novoa,
CrystEngComm, 2008, 10, 423.
3
interactions involving organic fluorine containing a C(sp )–F
9
1
L. Checinska and S. J. Grabowski, Chem. Phys., 2006, 327, 202.
0 J. Marten, W. Seichter, E. Weber and U. Bohme, CrystEngComm,
008, 10, 541.
1 D. Chopra and T. N. Guru Row, CrystEngComm, 2008, 10, 54.
bond. In addition to the formation of conventional N–H/O]C
2
and C–H/O]C H-bonds, it is the weak but directional C(sp )–
2
3
H/F–C(sp ) interactions, involving fluorine atoms, acting
1
cooperatively to generate unique packing motifs. This has
implications in the formation of the overall crystal structure
wherein these weak intermolecular H-bonds pack the molecules
utilizing the symmetry elements of the space groups. Of partic-
ular interest is the compound [IUPAC name: N-[2-(tri-
fluoromethyl)phenyl]benzamide], a mono-trifluoromethylated
benzanilide which crystallizes in the rare and uncommon
12 (a) M. D. Prasanna and T. N. Guru Row, Cryst. Eng., 2000, 3, 135; (b)
I. Saraogi, V. G. Vijay, S. Das, K. Sekar and T. N. Guru Row, Cryst.
Eng., 2003, 6, 69; (c) A. Robertazzi, F. Krull, E. W. Knappb and
P. Gamez, CrystEngComm, 2011, 13, 3293; (d) C. Estarellas,
A. Bauza, A. Frontera, D. Quinonero and P. M. Deya, Phys.
Chem. Chem. Phys., 2011, 13, 5696; (e) C. Garau, D. Quinonero,
A. Frontera, P. Ballester, A. Costa and P. M. Deya, New J. Chem.,
2
003, 27, 211; (f) R. E. Dawson, A. Hennig, D. P. Weimann,
D. Emery, V. Ravikumar, J. Montenegro, T. Takeuchi, S. Gabutti,
M. Mayor, J. Mareda, C. A. Schalley and S. Matile, Nat. Chem.,
2010, 2, 533; (g) M. Albrecht, M. Muller, O. Mergel, K. Rissanen
and A. Valkonen, Chem.–Eur. J., 2010, 16, 5062.
1
tetragonal non-centrosymmetric space group P4 wherein the
2
3
observed C(sp )–H/F–C(sp ) H-bonds are relatively short and
directional. Furthermore, another compound [IUPAC name: 3-
1
3 (a) R. Berger, G. Resnati, P. Metrangolo, E. Weber and J. Hulliger,
Chem. Soc. Rev., 2011, 40, 3496–3508, and references therein; (b)
D. Chopra and T. N. Guru Row, CrystEngComm, 2011, 13, 2175.
(
trifluoromethyl)-N-[4-(trifluoromethyl)phenyl]benzamide] crys-
tallizes in the rare orthorhombic centrosymmetric space group
2
3
14 (a) V. A Brunet and D. O. Hagan, Angew. Chem., Int. Ed., 2008, 47,
Pccn wherein C(sp )–H/F–C(sp ) H-bonds also play a pivotal
role in crystal packing. In addition, the presence of the lone-
pair/p interaction, wherein the aromatic ring is electron
1
2
179; (b) L. Hildebrandt, R. Dinnebier and M. Jansen, Inorg. Chem.,
006, 45, 3217; (c) M. S. Corbett, X. Liu, A. Sanyal and J. K. Snyder,
Tetrahedron Lett., 2003, 44, 931; (d) T. L. Arbeloa, F. L. Arbeloa and
1
988 | CrystEngComm, 2012, 14, 1972–1989
This journal is ª The Royal Society of Chemistry 2012

View Online
I. L. Arbeloa, J. Illum. Eng. Soc., 1996, 68, 149; (e) A. Alberola,
D. J. Eisler, L. Harvey and J. M. Rawson, CrystEngComm, 2011,
35 M. Nardelli, J. Appl. Crystallogr., 1995, 28, 569.
36 A. L. Spek, Acta Crystallogr., Sect. A: Found. Crystallogr., 1990, 46,
C34.
13, 1794; (f) J. C. Horng and D. P. Raleigh, J. Am. Chem. Soc.,
2
003, 125, 9286; (g) B. Bilgicer, A. Fichera and K. Kumar, J. Am.
37 (a) K. Ono, M. Tomura and K. Saito, Acta Crystallogr., Sect. E:
Struct. Rep. Online, 2008, 64, o2183; (b) J. Jia, X. Wang, Y. Zhang
and J. Wang, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2006,
62, o2683; (c) P. Szlachcic, B. Jarosz and K. Stadnicka, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 2010, 66, o488; (d)
H. Kim, H. Yang, J. S. Kim, S. Moon and T. H. Kim, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o2471; (e)
L. Chen, H. He and H. Peng, Acta Crystallogr., Sect. E: Struct.
Rep. Online, 2010, 66, o405; (f) H. C. Devarajegowda, S. B. Vepuri,
M. V. Vahini, H. D. Kavitha and H. K. Arunkashi, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o2237; (g)
H. Gallardo, E. Girotto and A. J. Bortoluzzi, Acta Crystallogr.,
Sect. E: Struct. Rep. Online, 2010, 66, o75; (h) H. Gallardo,
E. Girotto, A. J. Bortoluzzi and G. G. Terra, Acta Crystallogr.,
Sect. E: Struct. Rep. Online, 2009, 65, o2040; (i) L. A. Huck,
G. D. Potter, H. A. Jenkins, J. F. Britten and W. J. Leigh, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2009, 65, m602; (j)
N. Kanwal, E. A. Hussain and O. Sahin, Acta Crystallogr., Sect. E:
Struct. Rep. Online, 2010, 66, o1146; (k) Z. Kelesoglu,
O. Buyukgungor, C. Albayrakb and M. Odabasoglu, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2009, 65, o3245; (l)
I. Meskini, M. Daoudi, J. Daran, H. Zouihri and A. Kerbal, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o961; (m)
H. Pervez, M. S. Iqbal, N. Saira, M. Yaqub and M. N. Tahir, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o1749; (n)
M. Ramzan, H. Pervez, M. Yaqub and M. N. Tahir, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, o2387; (o)
J. E. Theodoro, O. E. Hernandez, J. Ellena, J. Duque and
R. S. Correa, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2009,
65, o1012; (p) J. M. Tobin and J. D. Masuda, Acta Crystallogr.,
Sect. E: Struct. Rep. Online, 2009, 65, o1217; (q) R. Xie, T. Zhang,
A. Cao and X. Mei, Acta Crystallogr., Sect. E: Struct. Rep. Online,
2010, 66, o2307; (r) J. Xu, W. Cheng, J. Yana and G. Quan, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2009, 65, o2377; (s)
T. Zheng and H. Sun, Acta Crystallogr., Sect. E: Struct. Rep.
Online, 2010, 66, m574.
Chem. Soc., 2001, 123, 4393; (h) H. P. Chiu, Y. Suzuki,
D. Gullickson, R. Ahmad, B. Kokona, R. Fairman and
R. P. Cheng, J. Am. Chem. Soc., 2006, 128, 15556; (i) F. R. Leroux,
B. Manteau1, J. P. Vors and S. Pazenok, Beilstein J. Org. Chem.,
2008, 4, 1; (j) D. J. Brauer, H. Burger and G. Pawelke, Inorg.
Chem., 1977, 16, 2305.
5 C. Jackel, M. Salwiczek and B. Koksch, Angew. Chem., Int. Ed., 2006,
1
1
1
4
5, 4198.
6 M. Fioroni, K. Burger, A. E. Mark and D. Roccatano, J. Phys. Chem.
B, 2003, 107, 4855.
7 R. Betageri, Y. Zhang, R. M. Zindell, D. Kuzmich, T. M. Kirrane,
J. Bentzien, M. Cardozo, A. J. Capolino, T. N. Fadra,
R. M. Nelson, Z. Paw, D. T. Shih, C. K. Shih, L. Z. Jelaska,
G. Nabozny and D. S. Thomson, Bioorg. Med. Chem. Lett., 2005,
1
5, 4761.
1
8 J. L. Kgokong, P. P. Smith and G. M. Matsabisa, Bioorg. Med.
Chem., 2005, 13, 2935.
9 O. Jeannin and M. Fourmigue, Chem.–Eur. J., 2006, 12, 2994.
0 J. Liu, N. L. Wendt and K. J. Boarman, Org. Lett., 2005, 7, 1007.
1 P. Cecchi, M. Berrettoni, M. Giorgetti, G. G. Lobbia, S. Calogero
and L. Stievano, Inorg. Chim. Acta, 2001, 318, 67.
2 (a) O. Jeannin, R. Clerac and M. Fourmigue, J. Am. Chem. Soc.,
2006, 128, 14649; (b) O. Jeannin, R. Clerac and M. Fourmigue,
CrystEngComm, 2007, 9, 488.
3 (a) X. Wang, F. B. Mallory, C. W. Mallory, P. A. Beckmann,
A. L. Rheingold and M. M. Francl, J. Phys. Chem. A, 2006, 110,
1
2
2
2
2
3
954; (b) P. A. Beckmann, J. Rosenberg, K. Nordstrom,
C. W. Mallory and F. B. Mallory, J. Phys. Chem. A, 2006, 110, 3947.
4 P. D. C. Dietzel and M. Jansen, Z. Anorg. Allg. Chem., 2004, 630, 1573.
5 J. A. K. Howard and H. A. Sparkes, CrystEngComm, 2008, 10, 502.
6 D. E. Braun, T. Gelbrich, V. Kahlenberg, G. Laus, J. Wieser and
U. J. Griesser, New J. Chem., 2008, 32, 1677.
7 V. Petricek, M. Dusek and L. Palatinus, Jana2000, 08/11/2007,
Institute of physics, Praha, Czech Republic, 2007.
8 CrystAlis CCD and CrystAlis RED, Version 1.171.33.31,Oxford
Diffraction Ltd, Abingdon, Oxfordshire, England, 2009
2
2
2
2
2
2
3
38 I. Dance, New J. Chem., 2003, 27, 22.
9 A. Altomare, G. Cascarano, C. Giacovazzo and A. Guagliardi, J.
Appl. Crystallogr., 1993, 26, 343.
0 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
39 TURBOMOLE V6.3 2011, a development of University of Karlsruhe
and Forschungszentrum Karlsruhe GmbH, 1989–2007, TURBO
MOLE GmbH, since 2007 http://www.turbomole.com.
6
4, 112.
40 M. Nishio, Phys. Chem. Chem. Phys., 2011, 13, 13873.
41 J. S. Murray, P. Lane, T. Clark and P. Politzer, J. Mol. Model, 2007,
13, 1033.
3
3
3
1 L. J. Farrugia, WinGX, J. Appl. Crystallogr., 1999, 32, 837.
2 L. J. Farrugia, J. Appl. Crystallogr., 1997, 30, 565.
3 D. M. Watkin, L. Pearce and C. K. Prout, CAMERON—A Molecular
Graphics Package. Chemical Crystallography Laboratory, University
of Oxford, UK, 1993.
42 P. Metrangolo, J. S. Murray, T. Pilati, P. Politzer, G. Resnati and
G. Terraneo, CrystEngComm, 2011, 13, 6593.
43 P. Metrangolo, J. S. Murray, T. Pilati, P. Politzer, G. Resnati and
G. Terraneo, Cryst. Growth Des., 2011, 11, 4238.
44 J. A. K. Howard, V. J. Hoy, D. O’Hagan and G. T. Smith,
Tetrahedron, 1996, 52, 12613.
3
4 C. F. Macrae, I. J. Bruno, J. A. Chisholm, P. R. Edgington,
P. McCabe, E. Pidcock, L. Rodriguez-Monge, R. Taylor, J. Streek
and P. A. Wood, J. Appl. Crystallogr., 2008, 41, 466.
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 1972–1989 | 1989