Evaluation of the role of isostructurality in fluorinated phenyl benzoates

Article abstract of DOI:10.1021/acs.cgd.7b00421

In this report, the occurrence of three-, two-, and one-dimensional (3D, 2D, and 1D) isostructurality in phenyl benzoate (D00) and their fluorinated analogues was investigated in terms of their molecular assembly in solid state structures. A onedimensional C-H?O=C chain is observed as a robust motif (～ -21 kJ/mol) in the formation of the supramolecular architectures in these isostructural compounds. The isomorphous crystal structures exhibit 3D isostructurality or vice versa. The crystal packing shows that weak intermolecular C-H ? F, C-H ? O, C- H ? π interactions, and π ? π stacking are the main contributors providing stability toward the crystal lattice. The nature and energetics of all the geometrically or energetically equivalent building blocks associated with similar or different intermolecular interactions delineate the role of different molecular pairs in the crystal structures. The fingerprint plots of the isostructural set of crystal structures help to understand the similarities and the differences in the various interatomic contacts. A comparison of these crystal structures with fluorinated N-phenyl benzamides shows the change in supramolecular assembly in terms of intermolecular interactions as well as the lattice energy due to the participation of a strong donor (N-H).

Full text of DOI:10.1021/acs.cgd.7b00421

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Article
Evaluation of the role of isostructurality in fluorinated phenyl benzoates
Dhananjay Dey, and Deepak Chopra
Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b00421 • Publication Date (Web): 07 Sep 2017
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Evaluation of the role of isostructurality in fluorinated phenyl benzoates
Dhananjay Deya, Deepak Chopraa*
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aCrystallography and Crystal Chemistry Laboratory, Department of Chemistry, Indian
Institute of Science Education and Research Bhopal, Bhauri, Bhopal-462066, Madhya
Pradesh, India.
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ABSTRACT
In this report, the occurrence of 3D, 2D and 1D isostructurality in phenyl benzoate (D00) and
their fluorinated analogues was investigated in terms of their molecular assembly in solid
state structures. Oneꢀdimensional CꢀH···O=C chain is observed as a robust motif (~ ꢀ21
kJ/mol) in the formation of the supramolecular architectures in these isostructural
compounds. The isomorphous crystal structures exhibit 3D isostructurality or viceꢀversa. The
crystal packing shows that weak intermolecular CꢀH···F, CꢀH···O, CꢀH···π interactions and
π···π stacking are the main contributors providing stability towards the crystal lattice. The
nature and energetics of all the geometrically or energetically equivalent building blocks
associated with similar or different intermolecular interactions delineate the role of different
molecular pairs in the crystal structures. The fingerprint plots of the isostructural set of
crystal structures helps to understand the similarities and the differences in the various
interatomic contacts. A comparison of these crystal structures with the fluorinated Nꢀphenyl
benzamides shows the change in supramolecular assembly in terms of intermolecular
interactions as well as the lattice energy due to the participation of a strong donor (NꢀH).
1. INTRODUCTION
The importance of organic fluorine [1ꢀ2] in supramolecular assembly is wellꢀrecognized,
especially in the field of crystal engineering [3ꢀ5]. Fluorinated compounds have an impact on
the chemical reactivity and the biological activity when compared to the nonꢀfluorianted
derivatives [6ꢀ7]. The substitution of hydrogen atom/atoms with fluorine changes the
chemical reactivity in various drugs and pharmaceuticals [8]. Fluorine can generate different
types of supramolecular motifs to build the crystal lattice via intermolecular CꢀH···F [9ꢀ11],
CꢀF···F [12ꢀ13] and CꢀF···π [14] interactions in the absence or presence of any strong donor
[15]. The major exercise in crystal engineering is dedicated towards the achievement of
desired features utilizing the various intermolecular interactions via the mutual assembly of
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the molecules in the crystal lattice [16ꢀ18]. The existence of two different crystal structures
with 3D or 2D or 1D structural similarity in their molecular arrangements is called
isostructurality [18ꢀ20]. The structural similarities in the molecular arrangement between the
two crystal structures can be shown as 1D molecular chain, 2D layer and 3D supramolecular
construct [18, 21]. Two crystal structures can be isomorphous [22ꢀ23] with similar space
group and identical unit cell parameters. In most of the cases, the isomorphous solidꢀstate
structures show 3D isostructurality [20]. Furthermore, it is not necessary that crystal
structures with 1D and 2D isostructurality will be isomorphous. Nath et al have discussed the
isomorphous and isostructural behaviour in the crystal structures of fuchsones compounds on
account of chloroꢀmethyl exchange [23]. The investigations on isostructurality and their
relevant applications are also of immense interest [20, 24ꢀ28]. Furthermore, isostructurality
can affect the mechanical property of the material i.e. two isostructural (need not be
isomorphous) compounds can show different mechanical properties [29ꢀ30]. The occurrence
of isostructurality is very common in similar type compounds with equivalent functionalities
like ꢀH, ꢀCH3, ꢀF, ꢀCl, ꢀBr and I [31ꢀ32].
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Our recent study, has established the occurrence of 3D isostructurality in the presence of
strong hydrogen bonds, namely NꢀH···N, associated with the presence of weak CꢀH···N [33],
CꢀH···F, CꢀH···π [34] interactions and π···π stacking in fluorinated Nꢀphenyl benzimidamide
compounds [24]. Previously, the investigation on the crystal structures of 4,5ʹꢀsubstituted
benzenesulfonamidoꢀ2ꢀpyridines shows the robustness of the supramolecular architectures
having centrosymmetric NꢀH···N dimers which lead to the existence of 3D isostructurality
[35]. It has been already observed that weak intermolecular interactions play an important
role in the formation of the crystal lattice in in situ cryocrystallized fluorinated benzoyl
chlorides [36], wherein the columnar molecular array, stabilized via the primary building
block (involving π···π stacking), are interlinked via the secondary supramolecular motifs like
C–H···O/F/Cl interactions [37] and halogen···halogen contacts. Thus, our aim of this work
was to investigate the isostructurality (3D, 2D and 1D) in the absence of any strong hydrogen
bond in fluorinated phenyl benzoates (FPB) where the crystal packing is governed mainly by
the weak intermolecular interactions.
2. EXPERIMENTAL
Phenyl benzoate and their fluoroꢀderivatives (Scheme 1) have been synthesized and
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characterized via HꢀNMR, FTIR spectroscopy, differential scanning calorimetry (DSC) and
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powder Xꢀray diffraction (Figures S1ꢀS11). The synthetic procedure was undertaken using
well established procedures [38] and provided in the ESI.
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2.1. Crystal Growth
The crystallization of the pure synthesized compounds has been performed via solvent
evaporation method in different polar, nonꢀpolar and polarꢀnon polar mixture of solvents
(HPLC grade) at various conditions (at temperatures 25°C and 4°C). The slow evaporation
method has been applied to get highꢀquality single crystals. In most of the cases, the crystals
were obtained from (dichloromethane and hexane mixture), (acetone and hexane mixture),
cyclohexane, and methanol solvent systems. For the low melting solid D22 (the melting point
is 32.8ºC), we have used in situ cryocrystallization [39] technique using OHCD to crystallize
this compound. The details of in situ cryocrystallization technique are available in the ESI of
our previous study [40].
2.2. Crystal Structure Determination and Modelling of Disorder
The crystal structures of the unsubstituted phenyl benzoate D00 [41ꢀ42] and FPBs namely
D01 [42], D02 [43] and D03 [42] are already reported in the literature. The reported crystal
data were collected at 298K, and hence we have again reꢀdetermined the crystal structures of
D00, D01, D02 and D03 at 100K. The details of crystal structure refinement are discussed in
the ESI. In the case of P21 and P212121 space group, the inversion twin refinement (refined as
twoꢀcomponent twin) has been performed using BASF command. Table S1 lists the details
of the structure refinement parameters for all the FPBs. The ORTEPs of all the FPBs with the
atomꢀnumbering are shown in Figure S12. The occupancies of the disordered fluorine atom
(connected with the carbon atom in the ortho and meta positions on the substituted benzene
ring) at the two positions were refined by using the PART command in SHELXL 2014 [44],
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namely F1A & F1B and F2A & F2B (‘A’ part contains the higher occupancy and ‘B” part
corresponds to the lower occupancy for that atom). The atomic positions of the carbon atom
(A and B) of the disordered benzene ring were fixed with EXYZ command and the
anisotropic displacement parameter for these two sites (A and B) of the carbon and fluorine
atom was fixed using the EADP command. In case of D20 (F1A and F1B), D22 (F2A and
F2B), D31 (F1A and F1B) and D32 (F1A and F1B), the fluorine atoms are positionally
disordered. The role of the disordered fluorine in the crystal packing has been explored
previously in the literature [45ꢀ46] where the fluorine atom exhibits positional disorder
mainly in case of ortho and meta substituted Nꢀphenyl benzamides. In the course of all
computational investigations, the atomic coordinates (with normalized CꢀH distance) of the
major conformer (PART A) were considered.
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3. RESULT AND DISCUSSION
In case of D01, D21 and D31, there is the formation of an intramolecular short CꢀF···OꢀC
contact (Figure S12) primarily when the fluorine atom is attached to the ortho carbon atom
of the substituted benzene ring (C1 > C6). The intramolecular F···O distances are 2.694(2) Å
in D01, 2.679 (2) Å in D21 and 2.559(2) Å in D31. The torsion angles present in the structure
and the dihedral angle between the two substituted benzene rings are listed in Table S2. All
the ten crystal structures have been analyzed based on their supramolecular architectures as
well as the presence of geometrically and energetically similar structural building blocks
present in the crystal packing. The intermolecular interaction energy and their components
(Coulombic, polarization, dispersion and repulsion) obtained from PIXEL method [47ꢀ48] are
given in ESI. Cg1 and Cg2, mentioned in the entire discussion, are the centroids of
corresponding benzene rings C1 > C6 and C7 > C12 respectively.
3.1. Structural Similarity Analysis
The structural similarities between unsubstituted phenyl benzoate (D00) and fluorinated
analogues have been investigated using XPac 2.0.2 program (version 2.0.2) [49ꢀ51],
introduced by Gelbrich and coꢀworkers. All the atomic coordinates (in crystal geometry)
except the hydrogen and fluorine atoms, were considered for the XPac analysis. This method
helps to identify the supramolecular construct and the extent of crystal packing similarity
(called as dissimilarity index x) in three dimensional (3D) or two dimensional (2D) or one
dimensional (1D) molecular arrangement between two crystal structures. It also provides
quantitative estimates to the dissimilarity parameters, namely, the stretch parameter (the
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magnitude by which the crystal packing of one structure is stretched in comparison to the
crystal packing of the other structure), the extent of the change in angles and planes between
two crystal structures. From the analysis, it is observed that some structures shows 3D crystal
packing similarity, some are related with each other via 2D similarity and in the maximum
cases, 1D (Figure S13) structural similarity is observed. This feature is due to the presence of
a CꢀH··O chain which is present in the parent structure D00. Figure 1 and Table 1 shows the
overall structural similarity amongst these eleven crystal structures. The 3D and 2D
isostructural combinations are shown with the red color box and indigo color box
respectively. The green color box indicates the similar combination (100% similarity)
between structures such as D00ꢀD00, D01ꢀD01 etc. The yellow color box shows the 1D
packing similarities with CꢀH···O chain. From the analysis, it is observed that the
dissimilarity index value is in the range of 2.5ꢀ5.3, 1.6ꢀ9.9 and 4.0ꢀ12.6 for 3D, 2D and 1D
isostructural pair of crystal structures respectively. In most of the 1D isostructural cases,
inspite of the high values of the “dissimilarity index”, the similarities do exist on account of
the presence of the common building block consisting of a 1D CꢀH···O chain.
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Figure 1. The map containing the structural similarity (3D, 2D, 1D and no similarity) for the
eleven crystal structures of FPB [the green color indicates the similar combination].
Table 1. The structural similarity (3D, 2D and 1D) parameters for the isostructural FPBs
Combination
Dissimilarity
index (x)
Stretch
Parameter (Å)
∆ a (°)
∆ p (°)
3D Isostructurality
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D21
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D31
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0.19
1.8
2.3
4.0
4.7
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2D Isostructurality
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D22
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D32
D02
D20
D21
D31
D33
D10
4.6
5.2
4.3
1.6
9.9
0.16
0.20
0.23
0.06
0.38
2.0
2.3
2.4
0.7
5.4
4.1
5.7
3.6
1.5
7.8
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1D Isostructurality (CꢀH···O chain)
D00
D00
D00
D00
D00
D01
D01
D01
D01
D01
D01
D01
D01
D02
D02
D02
D02
D02
D03
D03
D03
D10
D10
D10
D03
D20
D31
D32
D33
D02
D03
D20
D21
D22
D31
D32
D33
D03
D20
D21
D22
D31
D31
D32
D33
D20
D21
D31
4.0
12.9
11.5
9.4
0.12
0.59
0.40
0.12
0.09
0.03
0.02
0.49
0.61
0.58
0.30
0.02
0.01
0.01
0.46
0.58
0.55
0.27
0.28
0.00
0.03
0.02
0.14
0.17
1.5
10.1
9.0
6.2
5.9
5.4
3.5
8.6
8.9
9.9
7.4
8.2
7.9
8.2
3.9
4.4
4.8
2.4
10.1
4.9
4.7
4.8
4.7
5.4
3.7
8.0
7.2
7.0
6.5
4.4
6.3
8.0
8.2
7.9
6.6
9.6
9.1
7.6
6.4
6.4
4.9
4.2
9.2
4.1
3.5
7.8
7.7
5.9
8.8
7.3
7.2
11.8
12.1
12.7
9.9
12.6
12.0
11.2
7.5
8.1
6.8
4.9
13.7
6.4
5.9
9.2
8.9
8.0
3.2. 3D isostructurality between D00 and D01
The crystal structures of D00 and D01 are isomorphous in monoclinic P21/c space group with
Z = 4. In both cases, two molecules (associated with CꢀH···π and CꢀH···O interactions)
together act as a single unit (sandwich) and these units are arranged in a herringbone pattern
down the bc plane (Figure 2a and 2b). Along a axis the molecules form CꢀH···O chain,
(Figure S13) involving carbonyl oxygen (O2) and the aromatic hydrogen atom (H12). A
comparison between the crystal structures D00 and D01 reveals the presence of 3D
supramolecular construct (Figure 2c) with the dissimilarity index value of 4.5. It is observed
that there is no change in the supramolecular construct on incorporation of the fluorine atom
at the ortho position on the substituted benzene ring (C1 > C6). The stabilization energies for
all the molecular pairs (associated with the various intermolecular interactions) involved in
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3D isostructural D00ꢀD01 were determined using PIXEL method. Table S3 lists all the
extracted molecular pairs (with the decreasing order of stabilization energy). Each molecular
pair present in D00 is associated in a similar manner with a molecular pair of D01 (presence
of similar or different interactions). Figure 3 shows the equivalent building blocks present
between D00 and D01. The strongest molecular pairs [D00ꢀI (ꢀ24.1 kJ/mol)/D01ꢀI (ꢀ24.8
kJ/mol)] are associated with the weak intermolecular C8ꢀH8···O1 and C9ꢀH9···π interactions
(Figure 3a). In addition, the 3D isostructural compound D00ꢀD01 contains the 1D CꢀH···O
chain (molecular pair II) with stabilization energy of ~ ꢀ21 kJ/mol, having 31ꢀ33%
electrostatic contribution (Figure S14) to the total stabilization. The maximum equivalent
molecular pairs (Figure 3) [D00ꢀI/D01ꢀI, D00ꢀII/D01ꢀII, D00ꢀIII (ꢀ19.8kJ/mol) /D01ꢀIII (ꢀ
21.1kJ/mol), D00ꢀIV (ꢀ13.9kJ/mol)/D01ꢀIV (ꢀ15.2kJ/mol) , D00ꢀV (ꢀ10.6 kJ/mol)/D01ꢀVIII
(ꢀ10.4 kJ/mol), D00ꢀVI (ꢀ10.3 kJ/mol) / D01ꢀVII (ꢀ10.8 kJ/mol) and D00ꢀVIII (ꢀ6.3 kJ/mol)/
D01ꢀIX (ꢀ7.4kJ/mol)] are isoenergetic, except in the case of D00ꢀVII/D01ꢀV and D00ꢀ
IX/D01ꢀVI.
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Figure 2. The molecular arrangement in (a) D00 down the bc plane and (b) D01 down the bc
plane; (c) 3D supramolecular constructs obtained from XPac analysis for D00ꢀD01.
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Figure 3. The equivalent molecular pairs with their stabilization energies for the 3D
isostructural compounds D00ꢀD01.
The energetic contribution (electrostatics and dispersion) towards the total stabilization for all
the equivalent molecular pairs of isostructural compound D00ꢀD01 is shown in Figure S14.
In the case of D00ꢀIX (ꢀ5.8 kJ/mol), only H3···H3 contact (2.41Å) is present whereas, in
D01ꢀVI (ꢀ15.2 kJ/mol), there is a formation of C3ꢀH3···F1 dimer (Figure 3i) having short
H···F [9, 52] distance (2.44Å) and high directionality (162º). Hence, the electrostatic
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···C2
contribution is 38% more for D01ꢀVI in comparison to D00ꢀIX. The π···π stacking [C4
distance is 3.750Å] present in D00ꢀVII (ꢀ10.0 kJ/mol) is more offset compared to the π···π
stacking [C4···C2 distance is 3.519(2)Å] in D01ꢀV (ꢀ15.2 kJ/mol) (Figure 3g). As the
fluorinated benzene rings are more electron deficient, the electrostatic contribution is ꢀ
4.8kJ/mol (13%) more when compared to the interaction between two unsubstituted benzene
rings in D00ꢀVII.
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3.3. 3D and 2D isostructurality between D20, D21, D22 and D31
The single crystal Xꢀray diffraction study reveals that the crystal structures of D20, D21 and
D31 (Figure S12 and Table S1) are isomorphous in P212121 space group with Z = 4. In all
three cases, the molecules are assembled in a similar type of zigzag fashion (Figure S15)
down the bc plane. XPac analysis shows the presence of 3D supramolecular construct with
dissimilarity index of 2.5 for D20ꢀD21 (Figure 4a), 4.5 for D20ꢀD31 (Figure 4b) and 5.3 for
D21ꢀD31 (Figure 4c). The close distribution of the data points at low angle with lower
magnitude of stretch parameter in the plot of ꢁp vs ꢁa and x vs ꢁd, support the existence of
isostructural behaviour between these three crystal structures. All the equivalent building
blocks for the 3D isostructural D20ꢀD21ꢀD31 are shown in Figure 5. Interestingly, the low
melting solid D22 which crystallizes in P21/n with Z = 4, is also related to D20, D21 and D31
with 2D structural similarity with the dissimilarity index of 4.6 for D22ꢀD20 (Figure S16),
5.2 for D22ꢀD21 (Figure S17) and 4.3 for D22ꢀD31 (Figure S18). Table S4 lists all the
possible molecular pairs with their interaction energies for the crystal structures of D20, D21
D22 and D31.
The crystal packing of D22 (Figure S19) shows the zigzag molecular sheet associated with
CꢀH···F dimeric chain down the (015) and (01ꢀ5) planes. The molecular pairs and the
stabilization energy for the individual pairs in D22 are shown in Figure S20. The one
dimensional C12ꢀH12···O2 chain [D20ꢀI, D21ꢀII, D31ꢀII (Figure 5a) and D22ꢀIII (Figure
S20c)] is preserved in all these four cases and the corresponding stabilization energies are in
the range of ꢀ18.8 to ꢀ20.4 kJ/mol. The equivalent molecular pairs [D20ꢀII, D21ꢀI, D31ꢀI
(Figure 5b) and D22ꢀII (Figure S20b) are associated with C8ꢀH8···Cg2 and CꢀH···F
interactions having the stabilization energy of ~ ꢀ20 kJ/mol. In the case of D20ꢀII, D21ꢀI and
D22ꢀII there is a formation of the intermolecular F···O contact (involving meta fluorine with
the O1 atom) but in case of D31ꢀI this is absent. Hence, the electrostatic contribution is ~ 7%
more for D31ꢀI as compared to the other three equivalent molecular pairs (Figure 6).
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Figure 4. 3D supramolecular constructs obtained from XPac analysis for the isostructural
pairs (a) D20ꢀD21, (b) D20ꢀD31 and (c) D21ꢀD31.
The isoenergetic equivalent molecular pairs [D20ꢀIII, D21ꢀIII, D31ꢀIII (Figure 5c) and D22ꢀ
IV (Figure S20d)] associated with CꢀH···O and CꢀH···π has the energy of ꢀ17.3 kJ/mol (~
40% electrostatics and ~60% dispersion contribution). The molecular pairs IV (Figure 5d) of
the 3D isostructural compounds D20ꢀD21ꢀD31 are geometrically as well as energetically (~ ꢀ
13 kJ/mol) equivalent. The fifth set of equivalent molecular pairs are D20ꢀV, D21ꢀV and
D31ꢀV (Figure 5e); out of them D20ꢀV and D31ꢀV are isoenergetic (~ ꢀ9.0 kJ/mol)
associated with intermolecular CꢀH···O and short H···H contact. Interestingly, D21ꢀV (ꢀ6.9
kJ/mol) has a short (dH···F = 2.29Å) intermolecular CꢀH···F contact. Hence, the electrostatic
contribution for D21ꢀV is ~ 16% more as compared to the other two equivalent pairs.
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Figure 5. The equivalent molecular pairs for the 3D isostructural compounds D20ꢀD21ꢀD31.
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Figure 6. The energetic contributions of the equivalent molecular pairs for between D20,
D21, D31 and D22.
Subsequently, the dispersion contribution for D20ꢀV and D31ꢀV is ~ 16% more due to the
presence of short H···H contact (dH···H ~ 2.22Å). The VI (Figure 5f) and VII (Figure 5g)
molecular pairs of 3D isostructural D20ꢀD21ꢀD31 also geometrically equivalent with D22ꢀ
VIII (ꢀ5.1 kJ/mol) (Figure S20h) and D22ꢀIX (ꢀ5.1kJ/mol) (Figure S20i) respectively. The
strongest molecular pair D22ꢀI (ꢀ25.5 kJ/mol) (Figure S20a) and the other two
centrosymmetric CꢀH···F dimers [VI (ꢀ7.9 kJ/mol) (Figure S20e) and VII (ꢀ5.2 kJ/mol)
(Figure S20g)] are unique in comparison to the other molecular pairs present in D20, D21
and D31. In case of D22ꢀVII, it is observed that the dispersion contribution (89%) to the total
stabilization (ꢀ12.3kJ/mol) is very high in comparison to the electrostatic contribution (ꢀ0.3
kJ/mol) and also the repulsion component is 6 kJ/mol.
3.4. 2D structural similarity between D32 and D33
The compound D32 crystallizes in the monoclinic centrosymmetric P21/c space group (Z = 4)
whereas D33 crystallizes in the monoclinic centrosymmetric C2/c space group (Z = 8). In
both the cases, one fluorine atom is attached at the para position on the substituted benzene
ring (C2 > C12) but the other fluorine atom is attached at the meta and para position of the
substituted benzene ring (C1 > C6) for D32 and D33 respectively (Figure S12). Between
these two structures, two crystallographic lattice parameters (b and c) are similar and the third
one (a axis) is just double the other (D32). The orientation of the substituted benzene ring
(C2 > C12) of one structure [rotation antiꢀclockwise by 54.32 (3)º from the vertical position]
is different (Figure S21) from the other one [rotation clockꢀclockwise by 55.41(5)º from the
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vertical position]. In both the cases, the molecules were found to form a molecular sheet
(Figure S22a and S22b) down the ab plane, wherein the zigzag CꢀH···F chain [C4Aꢀ
H4A···F1A in D32 (Figure S22a) and C3ꢀH3···F1 in D33 (Figure S22b)] propagates along
the crystallographic b direction along with the 1D CꢀH···O (involving H12 with O2) chain in
parallel. In the same sheet of D32, the 1D CꢀH···O chain is connected to the neighboring Cꢀ
H···O chain in parallel utilizing the 21 screw axis via CꢀH···F interaction (involving H11 with
F2) and F···F contact [2.992(1)Å] (Figure S22a). Whereas, there is the formation of different
types of centrosymmetric CꢀH···F dimers (represented with different transparent color codes)
which connect two parallel aligned CꢀH···O chains in D33 (Figure S22b). There is a
formation of another molecular sheet [down the (0ꢀ11) plane and (011) plane in the case of
D32 and D33 respectively] associated with intermolecular CꢀH···π, C12ꢀH12···O1 and Cꢀ
H···F interactions (Figure S23a and S23b). In the case of D32, the acidic hydrogen H2A and
H5A interact with Cg1 and H8 and H11 interact with Cg2. Whereas in the case of D33, the
acidic hydrogen H2 and H5 interact with Cg1 and H8 and H11 interacts with Cg2. Also, it is
of interest to note that both the structures have BurgiꢀDunitz type [53ꢀ54] of
O=C(13)ꢂꢂꢂO(2)=C interaction (interaction between carbonyl carbon with carbonyl oxygen
atom) which also provides additional stability towards the crystal packing.
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Figure 7. 2D supramolecular constructs obtained from XPac analysis for D32ꢀD33.
The structural similarity analysis shows that these two structures are 2D isostructural (Figure
7) with dissimilarity index of 1.6. It has been observed that both the structures have some
energetically equivalent molecular building blocks. Table S5 lists the stabilization energies
and the geometry of the interactions involved in the molecular pairs (extracted from the
crystal packing) for the 2D isostructural compounds D32ꢀD33. The molecular pairs I (ꢀ28.0/ꢀ
27.6 kJ/mol), II (ꢀ23.4/ꢀ23.4 kJ/mol), III (ꢀ22.5/ꢀ22.5 kJ/mol) and VI (ꢀ4.7/ꢀ5.1 kJ/mol) of
D32ꢀD33 (Figures 8aꢀd) are isoenergetic. The orientation of the carbonyl group in D32ꢀII is
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opposite to D33ꢀII (Figure 8b). The electrostatic and the dispersion contributions (Figure
S24) for the isoenergetic molecular pairs are comparable). Figure S25 shows the molecular
pairs associated with CꢀH···F interactions (nonꢀcentrosymmetric and centrosymmetric) for
D32 and D33. These are D32ꢀIV (ꢀ8.2 kJ/mol), D32ꢀV (ꢀ6.3 kJ/mol), D33ꢀIV (ꢀ7.3 kJ/mol),
D33ꢀV (ꢀ6.2 kJ/mol) and D33ꢀVII (ꢀ4.6 kJ/mol) which also contributes further stability
towards the crystal packing. It is noteworthy that fluorineꢀbased CꢀH···F interactions provide
a significant (21ꢀ43%) electrostatic contribution towards the stabilization of the individual
molecular pairs.
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Figure 8. The equivalent molecular pairs with their stabilization energies for the 2D
isostructural compounds D32ꢀD33.
3.5. 1D and 2D Structural similarity with D02, D03, D10
Compound D02 crystallizes in P212121 and has one metaꢀfluorine atom on the benzene ring
(C1 > C6). It has 2D structural similarity with D10 with the dissimilarity index 9.2 (Figure
S26). Also this structure has 1D structural similarity with the other structures (Table 1),
namely D03, D20, D21, D22 and D31 due to the presence of the C12ꢀH12···O2 chain (Figure
9a) having the energy range of ꢀ18.9 to ꢀ21.8 kJ/mol, wherein the electrostatic contribution is
the range of 29ꢀ42% and the dispersion contribution is the range of 58ꢀ71%. Table S6 lists all
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the possible molecular pairs for D02, D03 and D10. There is a formation of another
molecular sheet (Figure 9b) down the bc plane normal to the C12ꢀH12···O2 chain (ac plane).
This sheet is associated with molecular building blocks II (ꢀ20.6 kJ/mol), III (ꢀ17.2kJ/mol),
IV (ꢀ16.1 kJ/mol) and VI (ꢀ5.4 kJ/mol). The molecular pairs II [associated with CꢀH···F and
CꢀH···π interaction] connect with each other via C3ꢀH3···O2 along a direction and with the
molecular pairs III (involving C10ꢀH10···O2 and C9ꢀH9···Cg1) and VI (involving F1 with
H10) along the c direction. The molecular pair III is isoenergetic with the equivalent
molecular pairs D20ꢀIII, D21ꢀIII, D31ꢀIII and D22ꢀIV. In addition to that, the D02ꢀV
(involving H11 with C9; ꢀ9.1kJ/mol) molecular pair also contributes towards the stabilization
in the crystal packing.
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Figure 9. The packing network of D02 showing (a) 1D CꢀH···O chain along a direction; (b)
the molecular sheet down the (ꢀ110) plane.
In case of D03 (space group C2/c), the molecules are connected to form a molecular sheet
(Figure 8) down the (10ꢀ1) plane. In this molecular sheet, parallel 1D C12ꢀH12···O2 (III; ꢀ
22.1kJ/mol) chains (along the b direction) are connected with each other via CꢀH···F motif
(involving F1 with H9, H10 and H11 and hence fluorine is a trifurcated acceptor). In addition
to that, there is the formation of a chain of dimers (Figure S27) associated with I (C6ꢀ
H6···O1 and C5ꢀH5···Cg2; ꢀ26.9kJ/mol) and V [C3ꢀH3···O2 and H2···H2 (1.97Å); ꢀ15.9
kJ/mol] down the (6 2 ꢀ5) plane. The chains are connected with centrosymmetric dimer II
(C8ꢀH8···Cg1 and C9ꢀH9···F1; ꢀ23.7 kJ/mol) via CꢀH···F [VII (ꢀ4.8 kJ/mol) and VIII (ꢀ4.8
kJ/mol)] interactions. The dimers IV are connected with each other via π···π stacking (ꢀ17.5
kJ/mol), the centroidꢀcentroid distance being 3.815(2) Å. The D03 has the 1D structural
similarity with D22, having the high dissimilarity index of 12.3. The geometrically equivalent
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molecular building blocks between D03 and D22 are the D03ꢀIII/D22ꢀIII and D03ꢀIV/D22ꢀI
(Figures 10, S20a, S20c and S27).
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Figure 10. Crystal packing of D03 showing the molecular sheet associated with parallel Cꢀ
H···O chains connected via trifurcated CꢀH···F interaction down the (10ꢀ1) plane.
Figure 11. Crystal packing of D10 showing (a) a molecular sheet associated with CꢀH···O
and π···π interactions down the bc plane, (b) 1D parallel CꢀH···O chains connected via Cꢀ
H···O and CꢀH···π interactions down the ac plane.
The compound D10 crystallizes in monoclinic space group P21 with Z = 2. In this case, the
molecules were found to form a molecular sheet down the bc plane (Figure 11) associated
with the molecular pairs I (involving C5ꢀH5···O2 and C4···C7 contact; ꢀ25.4 kJ/mol) and II
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(involving C10ꢀH10···O2 and C9ꢀH9···Cg2; ꢀ19.7 kJ/mol). Down the ac plane there is a
formation of CꢀH···O chain involving H12 with O2 (III; ꢀ18.8 kJ/mol). Such two parallel Cꢀ
H···O chains are connected with each other via the molecular pairs II and V (involving H11
with C10; ꢀ6.3kJ/mol). There is a 1D structural similarity (involving CꢀH···O chain) with D20
(the dissimilarity index is 9.2), D21 (the dissimilarity index is 8.9) and D31 (the dissimilarity
index is 8.0). The magnitude of the dihedral angles between the two substituted benzene rings
is high (> 61°) in case of D02, D10 and D22. Apart for these three structures, the dihedral
angles for the other structures in this series are in the range of 52ºꢀ58º. From the studied
crystal structures, it is observed that the 1D chain associated with the CꢀH···O interaction
always occurs between C12 (ortho carbon of the C2 > C12 ring)ꢀH12 and O2ꢀC13 (these two
are at opposite side of the molecular fragment C13ꢀO1ꢀC7ꢀC12).
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Table 2. The lattice energies (in kJ/mol) of the FPBs and Nꢀphenyl benzamides
Phenyl benzoates
Nꢀphenyl benzamides
Code
D00
D01
D02
D03
D10
D20
D21
D22
D31
D32
D33
ECoul
ꢀ26.5
ꢀ39.3
ꢀ38.8
ꢀ36.3
ꢀ36.3
ꢀ36.4
ꢀ40.2
ꢀ35.1
ꢀ38.7
ꢀ33.4
ꢀ33.7
EPol
EDisp
ERep
55.3
78.3
77.0
81.9
77.1
76.9
70.7
ꢀ71.1
80.8
74.0
79.6
ETot
ꢀ95.5
ꢀ105.7
ꢀ97.5
ꢀ96.0
ꢀ98.4
ꢀ96.4
ꢀ99.9
ꢀ98.2
ꢀ98.8
ꢀ97.4
ꢀ95.7
Code
DC0
DC1
ECoul
ꢀ46.4
ꢀ35.9
EPol
ꢀ22.1
ꢀ15.5
EDisp
ERep
80.9
62.8
ETot
ꢀ10.8
ꢀ15.3
ꢀ14.7
ꢀ15.6
ꢀ16.1
ꢀ14.3
ꢀ14.8
ꢀ15.1
ꢀ15.6
ꢀ14.1
ꢀ14.7
ꢀ113.6
ꢀ129.5
ꢀ121.0
ꢀ126.1
ꢀ123.1
ꢀ122.6
ꢀ115.7
ꢀ119.0
ꢀ125.2
ꢀ123.9
ꢀ126.9
ꢀ134.1
ꢀ120.0
ꢀ121.7
ꢀ109.5
DC3
ꢀ54.1
ꢀ20.9
ꢀ131.8
83.5
ꢀ123.3
DC5
ꢀ50.2
ꢀ36.4
ꢀ18.7
ꢀ17.2
ꢀ133.9
ꢀ120.9
79.5
66.1
ꢀ123.4
ꢀ108.6
DC10
DC15
ꢀ49.2
ꢀ18.0
ꢀ134.4
81.3
ꢀ120.3
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The discussion is focused on the variation in molecular assembly involving the weak
intermolecular interactions in the absence of any strong Hꢀbonds. As the phenyl benzoate and
their fluorinated analogues already have a strong acceptor (C=O), it is of interest to
substantiate the effect due to the participation of strong donor like NꢀH at the position of
phenoxy oxygen atom. Hence, we have compared the crystal packing features of similar type
of compounds, namely Nꢀphenyl benzamide [55] and their fluorinated derivatives [46, 56]
[Scheme 2 and Table S7] with our current study in terms of the associated nature and
energetics. There is a formation of a strong NꢀH···O hydrogenꢀbonded chain along with the
CꢀH···O interaction. It is noteworthy that 1D CꢀH···O chain which was already present in
phenyl benzoates (strong hydrogen bond is absent), was also preserved in Nꢀphenyl
benzamides (Figure S28a). The unsubstituted Nꢀphenyl benzamide (DC0) has 1D structural
similarity (containing the NꢀH···O chain) with the unsubstituted phenyl benzoates (D00) with
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dissimilarity index of 15.3 (stretch parameter = 0.39Å, δa = 5.1
º and δp = 14.4º).
Furthermore, we have performed the PIXEL analysis for some selected fluorinated Nꢀphenyl
benzamides (Table S8) including the unsubstituted compound DC0. From the crystal packing
analysis, it is observed that there are some similarities in the molecular arrangement between
two different classes of compounds. The dihedral angle between the two benzene rings in
DC0 is 62.8º, but after the addition of fluorine atom on phenyl ring, the magnitude of the
dihedral angle is either drastically reduced towards planarity (DC1 and DC10) or slightly
changed (DC3, DC5 and DC15). When the dihedral angle between the two substituted
benzene rings is close to 0º, the intermolecular CꢀH···O interaction forms with a distance
more than the sum of the van der Waals radii (> 2.72Å) of hydrogen and oxygen atom and
with reduced directionality. Whereas, the geometry of CꢀH···O interaction involved in 1D
chain in phenyl benzoates is totally different i.e., characterized by short H···O distance and
high directionality (144ºꢀ169º). The lattice energies for all the FPBs and selected fluorinated
Nꢀphenyl benzamides are tabulated in Table 2. The comparison between two different classes
of compounds having the fluorine substitution at the similar position ortho/meta/para is
shown in Figure S28ꢀS29. In most of the cases, the lattice energy of phenyl benzoates is in
the range of ꢀ95.5 to ꢀ105.7 kJ/mol. The stabilization energy of the molecular pair associated
with the strong NꢀH···O hydrogen bond and CꢀH···O interaction are in the range of – 41.7 to ꢀ
42.5kJ/mol for DC0, DC3, DC5 and DC15. Wherein, this stabilization energy is less for DC1
(ꢀ35.9kJ/mol) and DC10 (ꢀ33.8 kJ/mol) and subsequently, the lattice energy is also less (ꢀ108
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to ꢀ113 kJ/mol) compared to the other benzanilides (ꢀ120 to ꢀ124 kJ/mol). Although, DC1 and
DC10 have strong Hꢀbonds, the deviation in lattice energy is very less when compared to the
respective structures (D01 and D21) with similar H/F substitution. Thus, after the launch of a
strong donor (NꢀH) in comparison to those of phenyl benzoates, a relatively large change (ꢀ
26.2 kJ/mol) in the magnitude of the lattice energy is observed.
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Figure 12. Relative contribution of atom···atom contacts in the crystal packing of FPBs.
3.7. Hirshfeld Surface Analysis
Hirshfeld surface analysis [57] for the FPBs was performed using the program
CrystalExplorer 3.3 [58]. The fingerprint plots [59ꢀ60] obtained from the Hirshfeld surface
analysis are shown in Figures S30ꢀS32. The Figure S30 shows the overall fingerprint plots
for the 3D isostructural compounds D00ꢀD01 and their individual atom···atom contacts
(H···H, C···H, O···H and F···H). After the replacement of the aromatic hydrogen atom by the
fluorine atom, the contribution for the H···H contact is drastically changed from 43.9% (D00)
to 30.0% (D01). This deviation (13.9%) of the H···H contact is fulfilled by F···H contacts
(14.1% in D01) via the formation of CꢀH···F intermolecular interactions. Figure 12
represents the relative contribution of the various atom···atom contacts for phenyl benzoate
and their fluorinated analogues. The contribution of the H···H contact is in the range of 30.0ꢀ
33.4% and 17.5ꢀ27.7% for the mono fluoro and difluoroꢀsubstituted phenyl benzoates
respectively. The contribution of C···H contacts coming from the intermolecular CꢀH···C
interaction is in the range of 26.3ꢀ37.7%. In this case, there is no significant CꢀH···C contact
present in the crystal packing. The H···F contact contribution is also increased for the diꢀ
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fluorinated phenyl benzoates compared to the monoꢀfluoro analogues. The contribution from
the intermolecular F···O contact is in the range of 0.3ꢀ2.9%. Out of eleven fluorinated crystal
structures D22 (2.9%), D21 (2.1%) and D20 (2.0%) have the highest intermolecular F···O
[61ꢀ62] contribution towards their individual crystal packing. The compounds D01, D10, D32
and D33 do not contain any such type of contact in the crystal lattice. Hence the fingerprint
plots gives the similarities as well as the differences in terms of interatomic contacts for the
two isostructural compounds (1D or 2D or 3D) as well as for the other fluorinated analogues
(monoꢀfluoro and diꢀfluoro) discussed in the entire study.
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4. SUMMARY
In this work, eleven crystal structures of phenyl benzoate and their fluorinated derivatives
have been analyzed in terms of their molecular arrangement which exhibits isomorphism and
isostructurality in the solid state. The robustness of 1D CꢀH···O chain plays an important role
in the occurrence of isostructurality for fluorinated analogues. The molecular assembly are
mainly stabilized via intermolecular CꢀH···O, CꢀH···F, CꢀH···C interaction and π···π stacking
in the absence of any strong hydrogen bond. The crystal structures with 3D/2D/1D
isostructurality have isoenergetic or nonꢀisoenergetic equivalent building blocks with similar
or different types of intermolecular interactions. In most of the cases, the molecular pairs with
the CꢀH···O interaction, involved in 1D chain, are the strongest with the stabilization energy
of ~ ꢀ21 kJ/mol. This quantitative investigation provides detailed physical insights into the
approach of the molecules in the formation of various supramolecular construct (3D/2D/1D)
in accordance with their molecular flexibility and the pattern of H/F substitution. The
comparison with the fluoro substituted Nꢀphenyl benzamides also provides valuable
information about the occurrence of isostructurality. This is related to the method of
replacement of various functional groups in the molecule. Thus, the cooperative interplay
amongst the various intermolecular interactions (strong and weak) is a complex phenomenon,
but the crystal environment and the flexibility associated with the weak intermolecular
interactions is instrumental in the final geometrical characteristics and energetics of all the
observed contacts in the crystal.
ASSOCIATED CONTENTS
Supporting Information
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1HꢀNMR Spectra, PXRD, Crystallographic refinements tables, Intermolecular interactions
with the stabilization energy, Fingerprint plots from Hirshfeld surface analysis. This material
is available free of charge via the Internet at http://pubs.acs.org.
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ACKNOWLEDGEMENTS
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D. D. thanks IISER Bhopal for the research fellowship. D. C. and D. D. thank IISER Bhopal
for the research facilities, infrastructure and SERB for research funding.
AUTHOR INFORMATION
Corresponding Author
Eꢀmail: dchopra@iiserb.ac.in. Fax: +91 755 6692392.
Notes
The authors declare no competing financial interest.
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Manuscript title: Evaluation of the role of isostructurality in fluorinated phenyl benzoates
Authors: Dhananjay Dey and Deepak Chopra
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Synopsis
In this study, a total of eleven crystal structures of isomeric fluorinated phenyl benzoates
have been analyzed in terms of their molecular arrangement which exhibits the phenomenon
of isomorphism and isostructurality. The 1D CꢀH···O=C chain is observed as a robust motif
and plays an important role in the occurrence of isostructurality.
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