Computational Study of the Formation of Short Centrosymmetric N–H

Article pubs.acs.org/crystal

Computational Study of the Formation of Short Centrosymmetric N− H···S Supramolecular Synthon and Related Weak Interactions in Crystalline 1,2,4-Triazoles Dhananjay Dey,† T. P. Mohan,‡ B. Vishalakshi,§ and Deepak Chopra*,† †

Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Indore By-Pass Road, Bhauri, Bhopal 462066, Madhya Pradesh, India ‡ Rallis India, Ltd., Bangalore 560091, Karnataka, India § Department of Post-Graduate Studies and Research in Chemistry, Mangalore University, Mangalagangothri 574199, Karnataka, India S Supporting Information *

ABSTRACT: A comprehensive analysis of the crystal packing and the energetic features of a series of four biologically active molecules belonging to the family of substituted 4(benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4triazole-5-(4H)-thione derivatives have been performed based on the molecular conformation and the supramolecular packing. This involves the formation of a short centrosymmetric R22(8) N−H···S supramolecular synthon in the solid state, including the presence of C−H···S, C−H···O, C−H···N, C−H···F, C−H···Cl, C−F···F−C, C−Cl···Cl−C, and C−H···π intermolecular interactions along with π−π stacking to evaluate the role of noncovalent interactions in the crystal. The presence of such synthons has a substantial contribution toward the interaction energy (−18 to −20 kcal/mol) as obtained from the PIXEL calculation, wherein the Coulombic and polarization contribution are more significant than the dispersion contribution. The geometrical characteristics of such synthons favor short distance, and the population of related molecules having these geometries is rare as has been obtained from the Cambridge Structural Database (CSD). Furthermore, their interaction energies have been compared with those present in our molecules in the solid state. The topological characteristics of the N−H···S supramolecular synthon, in addition to related weak interactions, C−H···N, C−H···Cl, C−F···F−C, and C−Cl···Cl−C, have been estimated using the quantum theory of atoms in molecules (QTAIM). In addition, an analysis of the Hirshfeld surface and associated fingerprint plots of these four molecules also have provided a platform for the evaluation of the contribution of different atom···atom contacts, which contribute toward the packing of the molecules in solids.

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INTRODUCTION The study of noncovalent interactions1,2 is based on the complete understanding of the nature and energetics of different interactions, and its control is of extreme significance in the area of crystal engineering3−9 in order to design new solids having attractive properties.10−12 The process for the molecular aggregation of a compound depends on a complex phenomenon known as molecular recognition coming from various kinds of strong and weak noncovalent interaction, which are the key elements for the formation of a molecular crystal.13,14 The term supramolecular synthon is an important tool in crystal engineering for the design of supramolecular structures.15 The concept of a supramolecular synthon is obtained from the term synthon, as defined by Corey.16 The term supramolecular synthon plays a significant role in supramolecular synthesis. Supramolecular synthons are spatial arrangements of intermolecular noncovalent interactions that frequently occur in supramolecular structures.17 It is a welldefined linear connection between the molecular building blocks coming from the same components or different © XXXX American Chemical Society

components. Synthons are produced by the assembly of two molecules through molecular functionalities (like carboxylic acid, amides, thioamides, and alcohols containing both hydrogen bond acceptor and hydrogen bond donor) that interact with each other in a predictable manner. Supramolecular synthons are classified into two categories: supramolecular homosynthon (composed with identical functionalities) and supramolecular heterosynthon (composed with different functionalities).18,19 Heterocyclic compounds are widely distributed in nature and essential to life in various ways.20 1,2,4-Triazoles exhibit a broad range of biological activities.21 The 4-fluoro-3-phenoxyphenyl moiety has been a key component of many compounds, which exhibit potent pesticidal and herbicidal activity.22 In this article, four biologically active molecules, namely, 4-(benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4-triazole-5(4H)-thiReceived: July 23, 2014 Revised: September 16, 2014

A

dx.doi.org/10.1021/cg501103c | Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

Scheme 1

Table 1. Single Crystal Data Collection and Refinement compd

SB1

formula F.W. CCDC no. wavelength (Å) temperature (K) solvent system crystal size crystal system space group a (Å) b (Å) c (Å) α (deg) β (deg) γ (deg) volume (Å3) Z′ Z ρ (g/cm3) μ (mm−1) F(000) θmin, max hmin,max; kmin,max; lmin,max

C21H15FN4OS 390.43 977853 0.71073 298 (2) acetonitrile 0.30 × 0.10 × 0.10 monoclinic P21/c 11.7720(14) 5.1209(7) 31.018(4) 90 100.537(4) 90 1838.3(4) 1 4 1.411 0.206 808 2.01, 28.94 (−16, 13), (−6, 6), (−41, 42)

no. of reflections no. unique/observed reflections no. of parameters Rall, Robs wR2all, wR2obs Δρmin, max (e Å−3) G.O.F.

SB2

SB3

SB4

27691 4699/2954

C21H14F2N4OS 408.42 977852 0.71073 298 (2) methanol 0.20 × 0.10 × 0.40 triclinic P1̅ 9.6540(4) 9.8749(5) 21.2608(10) 86.568(2) 89.868(2) 70.302(2) 1904.47(2) 2 4 1.424 0.209 840 2.34, 25.00 (−11, 11), (−11, 11), (−25, 25) 63807 6702/4632

C21H14ClFN4OS 424.87 977851 0.71073 298 (2) DCM + hexane 0.20 × 0.06 × 0.04 triclinic P1̅ 9.6141(6) 9.9322(7) 22.0885(15) 91.263(2) 91.897(2) 108.972(2) 1992.3(2) 2 4 1.416 0.326 872 2.24, 29.13 (−12, 13), (−13, 13), (−30, 30) 76106 10738/6926

C27H19FN4O2S 482.52 977854 0.71073 298 (2) methanol 0.20 × 0.10 × 0.05 triclinic P1̅ 9.7483(4) 10.2085(4) 12.2350(4) 94.986(2) 99.205(2) 99.983(2) 1175.44(8) 1 2 1.363 0.179 500 2.04, 28.68 (−9, 13), (−13, 13), (−16, 16) 12911 6048/3884

253 0.1005, 0.0494 0.1281, 0.1063 −0.221, 0.287 1.062

523 0.0722, 0.0429 0.1235, 0.1113 −0.203, 0.280 1.049

527 0.0951, 0.0587 0.1743, 0.1507 −0.340, 0.477 1.023

316 0.0891, 0.0539 0.1779, 0.1518 −0.315, 0.323 1.033

differently in an organic environment, and its contribution in the context of crystal engineering is now widely established.27 In general, the packing and the structural motif of the synthesized compounds depends on a delicate balance of different types of supramolecular interactions either due to the presence of certain functional groups or by introduction of new functional groups in different portions of the molecule. Recently, the formation of N−H···S hydrogen bond has been a topic of intense focus in organic chemistry as well as in

one derivatives, have been synthesized and characterized by single-crystal X-ray diffraction (XRD), infrared spectroscopy (IR), 1H nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and powder XRD. All four compounds contain at least one F atom. The presence of the fluorine atom in the molecule is responsible for major changes in the physicochemical properties, the chemical reactivity, and the biological activity rather than the nonfluorinated analogues.23−26 Organic fluorine has been observed to behave B



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Figure 1. ORTEP of (a) SB1, (b) SB2, (c) SB3, and (d) SB4 drawn with 30% ellipsoidal probability. The dotted lines indicate the presence of intramolecular C−H···N and C−H···π hydrogen bonds within the molecule and intermolecular C−H···S and C−H···O hydrogen bonds between the molecules present in the asymmetric unit.

transition metal chemistry.28−30 In the complex ferredoxin, the active amide hydrogen bond donors were found to interact with the sulfur atom of the iron−sulfur cluster.31 In order to evaluate the biological function of the enzyme, it is of interest to understand the nature of the N−H···S hydrogen bond in molecular crystals.32 Vittal and co-workers have reported a polymorph of 4-pyridinethione based on the presence of a N− H···S hydrogen bond.33 From the experimental charge density study performed on salicylaldehyde thiosemicarbazone, it has been shown that the existence of high polarizability of the electron density of the free electron pair on the sulfur atom leads to the formation of multiple interactions, the most prominent being the presence of a centrosymmetric N−H···S hydrogen bond dimer.34 To get a better understanding of the contribution of intermolecular interactions toward the crystal packing, it is of significance to obtain quantitative insights into the nature and energetics of these interactions.35 The total lattice energy divided into their Coulombic, polarization, dispersion, and repulsion contribution, obtained from PIXEL36−42 calculations, also provides significant insights toward an understanding of the role of different intermolecular interactions toward the crystal packing. To recognize the formation of the N−H···S interaction as a key supramolecular

homosynthon, we have performed a detailed investigation of the Cambridge Structural Database (CSD version 5.35, 2013).43−47 PIXEL calculations for the evaluation of the interaction energies for this N−H···S synthon in these molecules were performed and compared with our current library of molecules. Furthermore, using the approach of QTAIM48,49 we have performed a detailed topological analysis for the N−H···S synthon to characterize the energetics associated with these interactions. All the above-mentioned computational procedures enable a quantitative understanding of the nature of weak intermolecular interactions involving different functional groups in crystals.

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EXPERIMENTAL SECTION

Synthesis. The procedure to synthesize the target compound 5 is known in the literature.50 The final product 5 was filtered and recrystallized from aqueous DMF (Scheme 1). Data for 1H NMR spectra are reported as follows: chemical shift (multiplicity, coupling constants, and number of hydrogens). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), m (multiplet); IR spectra were recorded on a FT-IR system (Spectrum BX) from PerkinElmer spectrometer and are reported in frequency of absorption (cm−1). Only selected IR absorbances are reported (Figures S1−S5, Supporting Information). C



Article

X-ray Crystallography. Single-crystal X-ray measurements were carried out on a Bruker D8 venture PHOTON 100 CMOS diffractometer using Mo Kα radiation (λ = 0.71073 Å) at 298(2) K. The crystal structures were solved by direct methods using SIR 9251 and refined by the full matrix least-squares method using SHELXL9752 present in the program suite WinGX.53 Empirical absorption correction was applied using SADABS.54 The non-hydrogen atoms are refined anisotropically, and the hydrogen atoms bonded to C and N atom were positioned geometrically and refined using a riding model with Uiso(H) = 1.2Ueq(C,N) for aromatic hydrogen and the hydrogen atoms connected to the double bond. The molecular connectivity was drawn using ORTEP32,55 and the crystal packing diagrams were generated using Mercury 3.1 (CCDC) program.56 Geometrical calculations were done using PARST57 and PLATON.58 The details of the data collection and the crystal structure refinement are shown in Table 1. Theoretical Calculations. Geometrical optimization of all the isolated molecules were performed through the DFT calculation using the basis set 6-31G** at the DFT/B3LYP level in TURBOMOLE59,60 taking the crystal geometry as a starting model. In order to evaluate the energies associated with various intermolecular interactions present in the crystal, PIXEL calculation have been carried out. The total lattice energy of the molecule is partitioned into the corresponding Coulombic, polarization, dispersion, and repulsion energies. The ab initio calculations for some selected dimers at the crystal geometry (with the hydrogen atoms moved to their neutral value) were performed at the DFT-B3LYP/6-311++G** level using Gaussian 09.61 The formatted checkpoint file (fchk) was used as input file for AIMALL (version 13.05.06)62 calculation. The electron density features at the bond critical points, which are computed, is as follows: (i) electron density (ρb), (ii) Laplacian (∇2ρb), (iii) local potential energy (Vb), and (iv) kinetic energy density (Gb). The dissociation energies for the different intermolecular interactions were determined using two empirical approaches: (i) DEV(int) = −0.5Vb (in au)63−68 and (ii) DEG(int) = 0.429Gb (in au);69,70 where DEint is the dissociation energy of the interaction. Vb and Gb are local potential and kinetic energy density at the bond critical points (BCP), respectively. Hirsfeld Surface Analysis. The Hirshfeld surface analysis71−73 was generated, and 2D fingerprint plots were performed using CrystalExplorer 3.1.74 Fingerprint plot is a 2D mapping that encapsulates quantitatively the nature and the type of intermolecular interaction experienced by a molecule in the crystalline environment in a convenient graphical format, which is unique for a given crystal structure.75 In addition, fingerprint plots help to identify the similarities and dissimilarities between related crystal structures.

Scheme 2

to syn through the substitution of aromatic hydrogen by F and Cl atom in the para position and −OPh group in the meta position of the phenyl ring, respectively. All the molecules contain a relatively strong acceptor (SC group) and a strong donor (N−H). Table S1, Supporting Information, shows selected torsion angles obtained from experiment and then compared with the values obtained from the DFT calculation with the 6-31G** basis set. Finally, the plot of the molecular overlay diagram (Figure S6, Supporting Information) for each molecule gives a comparison of the molecular conformation in the solid in comparison to the conformation obtained after the optimization of the crystal geometry. From overlay, it is clear that the phenyl ring, corresponding to the torsion τ5 in the gas phase for all the molecules, is in the same plane with the triazole ring. This is because of the resonance between the triazole ring and the phenyl ring via the CN double bond. Table 2 lists all the relevant intra- and intermolecular hydrogen bonds present in the crystal packing (with the hydrogen atoms moved to neutron values). The geometrical restriction placed on the intermolecular H-bonds are the sum of the van der Waals radii +0.4 Å, and the directionality is greater than 110°.76 (E)-4-(Benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4-triazole-5(4H)-thione (SB1). In this study, it has been observed that the crystal packing of these heterocyclic compounds containing the 1,2,4-triazole ring has been stabilized via strong N−H···S,77−81 weak C−H···S,82−84 C−H···O,85−95 C−H···N,96−99 C−H···F,100−102 and C− H···π103−108 intermolecular interactions and π−π stacking.108−110 The most interesting features of these four molecules are (1) conformational variation of the common moiety of the molecule due to the substitution of the aromatic hydrogen atom by other atoms or functional groups and (2) the presence of centrosymmetric supramolecular synthon with short N−H···S distance between the strong amide donor (N− H) and strong acceptor (S atom). Compound SB1 crystallizes in monoclinic centrosymmetric space group P21/c with one molecule in the asymmetric unit having an intramolecular C− H···N hydrogen bond (involving H10 with N4) providing stability toward the molecular conformation (Figure 1a and Table 2). All the molecular pairs extracted from PIXEL calculation, have been arranged in order of their decreasing interaction energy. The molecules related to each other by an inversion center result in the formation of a centrosymmetric supramolecular synthon R22(8), consisting of an amino group of the triazole ring of one molecule and the sulfur atom connected with the doubly bonded carbon atom of the triazole ring of other molecule, via strong N−H···S hydrogen bond (H···S distance = 2.25 Å, involving H2 with S1). The stabilization energy is −19.8 kcal/mol evaluated from PIXEL, wherein the Coulombic (47%) and polarization (36%)

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RESULTS AND DISCUSSION ORTEP diagram of the synthesized molecules have been shown in Figure 1. All molecules have a common triazole ring, which has been connected with a 4-fluoro-3-phenoxyphenyl group through the carbon atom (C13 or C34) of the triazole ring. Another part of the molecule is the benzylidene moiety attached with the N atom (N3 or N7). The molecule contains different HB acceptors (−F, −O−, S, and N) and HB donor (amide N−H in triazole ring and aromatic hydrogen). The molecular conformation is represented by five different torsion angles, indicated by symbols τ1, τ2, τ3, τ4, and τ5, respectively (Scheme 2). SB1 and SB4 contain one molecule in the asymmetric unit, but SB2 and SB3 have two molecules in the asymmetric unit. It is observed that the two molecules present in the asymmetric unit differ mainly due to variations in the torsion τ1 and τ5 (Figure S6, Supporting Information), respectively. In SB1, the molecular conformation is anti with respect to the C11−C13 bond (the orientation of −OPh group with respect to the benzylidene moiety). However, in the case of SB2, SB3, and SB4, the conformation is changed from anti D



Article

Table 2. Interaction Energy (in kcal/mol) and Centroid−Centroid Distance for Dimersa motifs

symmetry code

SB1 (P21/c) I −x + 1, −y + 3, −z II x, y + 1, z

centroid−centroid distance (Å)

Ecoul

Epol

Edisp

Erep

Etot

11.301 5.121

−20.0 −4.4

−15.8 −2.3

−6.9 −17.3

22.8 9.8

−19.9 −14.2

III IV

−x, −y + 2, −z −x + 1, y−1/2, −z + 1/2

11.854 7.532

−5.5 −1.9

−2.6 −1.1

−7.8 −10.1

7.3 5.4

−8.6 −7.7

V VI SB2 (P1̅) I (AB)

x + 1, y−1, z x + 1, y, z

12.838 11.772

−1.1 −1.4

−0.3 −0.4

−3.2 −2.9

1.3 1.8

−3.3 −2.9

−x + 1, −y + 1, −z + 1

12.317

−19.1

−15.2

−7.0

21.7

−19.6

II (AB)

x + 1, y, z

4.915

−6.4

−3.3

−20.4

12.6

−17.5

III (AB)

x, y, z

4.769

−5.4

−2.8

−21.1

12.4

−16.9

IV (AA)

x, y + 1, z

9.875

−4.3

−1.8

−7.9

6.4

−7.6

V (AA) VI (BB) VII (BB)

−x + 1, −y + 2, −z + 1 −x, −y + 2, −z + 1 x, y − 1, z

11.211 11.302 9.875

−4.2 −4.0 −1.4

−1.5 −1.5 −0.9

−6.3 −5.7 −5.8

6.5 5.5 2.7

−5.5 −5.7 −5.4

VIII (BB)

−x, −y + 1, −z

11.849

−0.7

−0.3

−4.0

1.5

−3.5

IX (AA)

−x + 1, −y + 1, −z

11.901

−0.3

−0.3

−3.4

1.0

−3.0

SB3 (P1̅) I (AB)

−x + 1, −y + 1, −z

12.675

−18.7

−14.4

−6.7

21.0

−18.8

II (AB)

x, y, z

4.890

−7.1

−3.6

−21.8

14.1

−18.4

III (AB)

x − 1, y, z

4.726

−6.1

−3.1

−23.2

14.5

−17.9

IV (BB)

x, y + 1, z

9.932

−4.1

−1.7

−7.8

6.2

−7.4

V (AA) VI (AA)

−x + 1, −y, −z x, y + 1, z

11.743 9.932

−4.0 −1.4

−1.3 −0.6

−5.8 −5.2

5.2 1.7

−5.9 −5.5

VII (BB) VIII (BB)

−x + 2, −y, −z −x + 2, −y + 1, −z + 1

11.903 12.227

−4.3 −1.4

−2.2 −0.6

−6.8 −5.5

8.5 2.9

−4.8 −4.6

IX (AA)

−x + 1, −y + 1, −z + 1

12.391

−0.8

−0.3

−4.5

1.9

−3.7

X (AB)

−x + 2, −y + 1, −z + 1

12.483

−0.9

−0.8

−4.1

2.9

−2.9

SB4 (P1)̅ I

−x + 2, −y + 1, −z

4.926

−8.7

−3.2

−29.6

15.5

−26.0

E

possible involved interactions

geometry (Å/deg)b

N2−H2···S1 Cg2···Cg3 π (C3−C2)···π (C5−C6) C15−H15···S1 C20−H20···S1 C6−H6···F1 C8−F1···π (C8−C9) C19−H19···O1 C19−H19···N1

2.25, 169 3.675(3) 3.485(3) 3.03, 128 2.84, 155 2.76, 124 3.18, 156 2.60, 131 2.58, 139

N2−H2···S2 N6−H6···S1 C2−H2A···F2 Cg3···π (C31) C3−H3···Cg1′ C33−H33···O1 C6−H6A···Cg1′ Cg2···Cg3′ C15−H15···F1 C21−H21···F1 C21−H21···O1 C20−H20···Cg1 C9−H9···N1 C30−H30···N5 C36−H36···F2 C23−H23···Cg4′ C25−H25···F4 F4···F4 C5−H5···F3 F3···F3

2.26, 167 2.28, 168 2.66, 168 3.362(3)c 2.65, 147 2.50, 135 2.59, 143 3.906(3) 2.38, 153 2.45, 150 2.68, 148 2.85, 132 2.57, 146 2.60, 154 2.56, 139 2.92, 133 2.66, 126 3.013(3), 97 (I)d 2.79, 123 3.079(4), 98 (I)d

N2−H2···S2 N6−H6···S1 C15A−H15A···S2 C26−H26···Cg1 Cg3′ ···π (C10) C20−H20···π (C41) C23−H23···Cg1 Cg3···Cg2′ C12−H12···O2 C36−H36···F2 C42−H42···F2 C42−H42···O2 C41−H41···π (C23) C9−H9···N1 C15A−H15A···F1 C21−H21···F1 C30−H30···N5 C39−H39···Cl2 C25−H25···Cl2 Cl2···Cl2 C4−H4···Cl1 Cl1···Cl1 C24−H24···Cl1 C4−H4···Cl2

2.27, 169 2.28, 166 2.80, 126 2.62. 143 3.413(3)c 3.06, 137 2.58, 146 3.716(4) 2.57, 126 2.47, 144 2.33, 148 2.66, 144 2.80, 151 2.60, 145 2.56, 139 2.77, 120 2.57, 162 3.00, 134 3.20, 137 3.792(3), 93 (I)d 3.23, 137 3.806(4), 99 (I)d 2.64, 163 2.97, 123

Cg3···Cg5 C12−H12···O2 C21−H21···Cg1

3.752(4) 2.67, 132 3.07, 141



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Table 2. continued motifs

symmetry code

SB4 (P1̅) II III IV V

−x −x −x −x

VI VII VIII

x, y + 1, z −x + 2, −y, −z + 1 −x + 1, −y, −z

+ + + +

3, 1, 2, 2,

−y −y −y −y

+ + + +

1, 1, 1, 2,

−z + 1 −z −z + 1 −z

centroid−centroid distance (Å)

Ecoul

Epol

Edisp

Erep

Etot

13.273 8.106 8.108 11.896

−17.0 −2.3 −2.3 −2.9

−13.1 −1.2 −1.7 −1.0

−6.8 −15.0 −12.2 −8.4

19.6 6.7 5.7 3.7

−17.3 −11.8 −10.5 −8.6

10.209 13.366 11.063

−1.5 −2.0 −1.1

−0.7 −0.5 −0.5

−6.5 −4.7 −4.1

3.4 2.4 1.8

−5.3 −4.8 −3.9

possible involved interactions N2−H2···S1 C25−H25···F1 C17−H17···N1 C27−H27···π (C19) C26−H26···π (C16) C18−H18···F1 C9−H9···N1 C3−H3···F1

geometry (Å/deg)b 2.31, 2.48, 2.53, 2.95, 2.91, 2.39, 2.86, 2.57,

159 124 160 149 152 155 127 131

a

Cg1: C1−C2−C3−C4−C5−C6. Cg2: C7−C8−C9−C10−C11−C12. Cg3: C13−N1−N2−C14−N3. Cg4: C16−C17−C18−C19−C20−C21. Cg1′: C22−C23−C24−C25−C26−C27. Cg2′: C28−C29−C30−C31−C32−C33. Cg3′: C34−N5−N6−C35−N7. Cg4′: C37−C38−C39−C40− C41−C42. bNeutron values are given for all D−H···A interaction. cGeometry from centroid of the related ring for the corresponding interaction. d Type I halogen···halogen contacts.

Figure 2. Molecular pairs of SB1 in decreasing order of energy.

(E)-3-(4-Fluoro-3-phenoxyphenyl)-4-((4fluorobenzylidene)amino)-1H-1,2,4-triazole-5(4H)-thione (SB2). Compound SB2 crystallizes in the triclinic centrosymmetric P1̅ space group with two molecules (A and B) in the asymmetric unit interacting with each other via weak intermolecular C−H···O and C−H···π hydrogen bonds and π−π stacking (Figure 1b). Both the molecules A and B present in the asymmetric unit form molecular layers by head to head and tail to tail dimers via short and highly directional N−H···S and weak C−H···F hydrogen bonds (Figure S8, Supporting Information). Molecule A interacts via weak C−H···F, C−H···O, and C− H···π , whereas molecule B interacts via C−H···N, C−H···F, and C−H···π intermolecular interactions. The alternate ABAB layers are linked down the ac plane (Figure S9, Supporting Information) via strong N−H···S and weak C−H···F hydrogen bonds. The strong and highly directional N−H···S hydrogen bonds (H···S distances = 2.26 and 2.28 Å, involving H2 and H6 with S2 and S1, respectively) results in a centrosymmetric supramolecular synthon R22(8). The stabilization energy of the molecular pair is −19.6 kcal/mol [Figure 3(I)]. Along the aaxis, C−H···F (involving H2A with F2) and C−H···π intermolecular interactions form a heteromolecular dimer (with the stabilization energy being −17.4 kcal/mol; 21% Coulombic and 11% polarization contribution) [Figure 3(II)]. The molecules A and B present in the asymmetric unit were

contribution is greater than the dispersion (17%) contribution of the dimer [Figure 2(I)]. Another molecular pair, the interaction energy being −14.2 kcal/mol, is formed via π−π molecular stacking; the centroid−centroid distance is 3.675(3) Å between the triazole ring (Cg3) and the phenyl ring (Cg2) along with a displaced π−π stacking (involving C3−C2 with C5−C6) and C−H···S (involving H15 with S1) intermolecular interaction [Figure 2(II)]. Across the center of symmetry, two molecules were found to form a molecular dimer (−8.8 kcal/mol) through the C−H···S hydrogen bond (involving H20 with S1) [Figure 2(III)]. F1 atom interacts with H6 (C−H···F) as well as C8−C9 bond of the phenyl ring to produce a dimer [Figure 2(IV)] with interaction energy of −7.7 kcal/mol along the 21 screw axis. In addition to this molecular dimer, two other molecular pairs [Figure 2(V,VI)] having an interaction energy of −3.3 and −2.9 kcal/mol for the C−H···O (H19 interacting with O1 of the −OPh group) and C−H···N (H19 interacting with N1 of the triazole ring) interaction provide additional stability. In the crystal packing, the dimer formed via N−H···S supramolecular synthon (I) is connected with the adjacent set via C−H···O intermolecular interaction (V) across the center of inversion down the ac plane (Figure S7a, Supporting Information). Furthermore, the molecular pairs II and III together formed a zigzag array down the bc plane (Figure S7b, Supporting Information). F



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Figure 3. Molecular pairs of SB2 with decreasing interaction energy.


found to form a molecular dimer via π−π stacking, C−H···S (involving H15 with S2), C−H···O (H33 with O1), and C−

H···π (H6A interacting with Cg1′) with interaction energy −16.9 kcal/mol, with 18% Coulombic and 10% polarization G



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weak C−H···Cl hydrogen bonds. Across the center of inversion the strong (with a short distance 2.27 Å) and highly directional (169°) N−H···S (involving H2 with S2 and H6 with S1) hydrogen bond was found to produce a centrosymmetric supramolecular synthon R22(8) [Figure 4(I)] having energy of −18.8 kcal/mol (47% Coulombic and 36% polarization contributions) evaluated from PIXEL. It is noteworthy that the molecular stacking in the asymmetric unit is stabilized via weak C−H···S (involving S2 with H15A) and C−H···π (involving H26 and H20 with Cg1 and Cg4′, respectively) interactions [Figure 4(II)], the energetic gain being sufficiently high (−18.4 kcal/mol; 21% Coulombic and 11% polarization contributions). A slightly less energetic molecular pair generated between A and B via π···π stacking (Cg2···Cg3′), C−H···π (H23 atom interacting with Cg1), and weak C−H···O (involving H12 with O2) is also present in the crystal, the interaction energy being 17.8 kcal/mol; 18% Coulombic and 10% polarization contributions [Figure 4(III)]. In addition, the molecule B forms a dimer [Figures 4(IV) and S11, Supporting Information], involving bifurcated acceptor F2, with H36 and H42 via weak C−H···F hydrogen bonds and bifurcated donor H42 with acceptor O2 and F2, via C−H···O and C−H···F, respectively, with interaction energy of 7.4 kcal/mol (30% Coulombic and 12% polarization contributions) propagating along the crystallographic b-axis. Across the center of inversion, A molecules were found to form a homodimer [Figure 4(V)] (−5.9 kcal/mol: 36% Coulombic and 11% polarization contributions) through the weak C−H···N hydrogen bond, involving H9 with N1. The interaction energy associated with C−H···F hydrogen bonds involving a bifurcated acceptor F1, with H15A and H21, between molecules A, is −5.5 kcal/mol [Figure 4(VI)] highlights the role of organic fluorine in crystal packing. Furthermore, across the center of inversion, a homodimer, having interaction energy of −4.7 kcal/mol (32% Coulombic

contributions [Figure 3(III)]. A bifurcated C−H···F hydrogen bond (H15 and H21 with the acceptor F1) along with C−H··· O and C−H···π intermolecular interactions formed a homodimer (AA) [Figure 3(IV)], pairing energy −7.7 kcal/ mol (30% Coulombic and 12% polarization contribution) along the b-axis (Figure S9, Supporting Information). Across the center of inversion, the N1 atom of the triazole ring interacts with aromatic H9 atom to form a centrosymmetric dimer (−5.6 kcal/mol) [Figure 3(V)] with 35% Coulombic and 12% polarization contribution. Another molecular pair comparable in energy with the earlier one forms a centrosymmetric dimer via C−H···N hydrogen bond (H30 interacting with N5) [Figure 3(VI) and Figure S10, Supporting Information]. In addition to that, C−H···F (H36 interacting with F2) and C−H···π (involving H23 with Cg4′) are involved in the formation of a homodimer (BB) [Figure 3(VI)] with comparable energy along the b-axis (Figure S9, Supporting Information). The other two molecular pairs having energy between −3.5 to −3.0 kcal/mol involves the presence of C−H···F and C−F···F−C contacts in the crystal stucture [Figure 3(VIII, IX)]. (E)-4-((4-Chlorobenzylidene) amino)-3-(4-fluoro-3phenoxyphenyl)-1H-1,2,4-triazole-5(4H)-thione (SB3). Compound SB3 crystallizes in the triclinic centrosymmetric P1̅ space group with two molecules (A and B) in the asymmetric unit connected via weak intermolecular C−H···π and C−H···S noncovalent interactions (Figure 1c). Similar kinds of molecular layers utilizing head to head and tail to tail dimers were formed via strong N−H···S and weak C−H···Cl hydrogen bonds (Figure S11, Supporting Information). Molecules A interact with each other via weak C−H···N, C− H···F, and C−H···Cl hydrogen bonds, whereas molecules B are interacting via weak C−H···F, C−H···O, C−H···N, and C− H···π hydrogen bonds. The alternate ABAB layers are interconnected down the bc plane via strong N−H···S and H



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Figure 6. Comparison of the crystal packing between (a) SB2 and (b) SB3. The Y groups do not interact due to conformational change.

centrosymmetric dimer [Figure 5(IV)] and finally produces a molecular chain down the bc plane (Figure S13b, Supporting Information). The discussion of the crystal packing of the four molecules present some interesting features. If we consider the benzylidene moiety being represented as X and the 4-fluoro3-phenoxyphenyl part as Y, then in the case of the fluoroderivative (SB2), the X part is connected with the X part via C−H···F intermolecular interactions down the ac plane, and there is no interaction between Y groups resulting in the formation of a sheet-like structure. The sheets are connected via strong N−H···S hydrogen bonds (Figure 6a). However, in the case of the Cl derivative (SB3), one part (X or Y) is connected with the unlike part (Y or X) via C−H···Cl intermolecular interaction, and finally, a cyclic structure was formed. Those were interconnected via a strong N−H···S hydrogen bond (Figure 6b). Table 3 lists the total lattice energy of the individual compounds in the range of −49 to −52 kcal/mol where the

and 16% polarization contributions) was formed between the B molecules through the involvement of weak C−H···N interaction (involving H30 with N5 atom of the triazole ring) [Figures 4(VII) and S12, Supporting Information]. Again, across the center of inversion, a molecular pair [Figure 4(VIII)] wherein a weak intermolecular interaction C−H···Cl (H39 with Cl2) stabilizes the crystal packing, the interaction energy being −4.4 kcal/mol. The intermolecular interaction energies of the other two molecular pairs [Figure 4(IX,X)] (involving C−H···Cl hydrogen bonds) were found to lie between −3.7 to −2.9 kcal/mol, which indicate weak but significant contribution toward the crystal packing. (E)-3-(4-Fluoro-3-phenoxyphenyl)-4-((3phenoxybenzylidene)amino)-1H-1,2,4-triazole-5(4H)thione (SB4). Compound SB4 crystallizes in the triclinic centrosymmetric P1̅ space group with one molecule in the asymmetric unit (Z = 2). The asymmetric unit is stabilized by the C−H···N intramolecular hydrogen bond and a C−H···π (H5 atom interacts with centroid Cg4) hydrogen bond (Figure 1d). Across the center of symmetry, π···π stacking (with the interplanar distance being 3.752(4)Å between the rings Cg3 and Cg5), C12−H12···O2, and one C−H···π (involving H21 with Cg1) intermolecular interaction generated a molecular dimer [Figure 5(I)]; the interaction energy is −26 kcal/mol; 21% Coulombic and 8% polarization contributions. The molecules were found to pack in the lattice through the presence of strong N−H···S (H···S distance = 2.31 Å) hydrogen bond as a primary structure-directing element forming a centrosymmetric supramolecular synthon R22(8) (−17.3 kcal/mol; 46% Coulombic and 35% polarization contributions) [Figure 5(II)]. The molecules have been found to form a centrosymmetric dimer [Figure 5(III)] through C−H···F interaction (involving H25 with F1) with the interaction energy −11.8 kcal/mol, and these dimers were found to be connected to a similar dimer present in the crystal packing either by N−H···S hydrogen bond (involving H2 with S1) or C−H···π intermolecular interactions (involving H26 and H27 with the Cg4) [Figure 5(V)] and formed a molecular sheet down the ab plane (Figure S13a, Supporting Information). In addition to that, the molecules have been found to constitute a centrosymmetric molecular dimer through C3−H3···F1 intermolecular [−3.9 kcal/mol, Figure 5(VIII)] interaction, and this dimer is further connected with other molecules through the C17−H17···N1 interaction, with the interaction energy being −10.5 kcal/mol to form a

Table 3. Lattice Energy (in kcal/mol) of the Individual Compounds code

Ecoul

Epol

Edisp

Erep

Etot

SB1 SB2 SB3 SB4

−22.1 −21.3 −22.0 −20.6

−13.3 −13.7 −13.5 −11.5

−51.5 −45.4 −48.1 −53.7

37.7 34.2 36.8 34.0

−49.2 −46.2 −46.8 −51.8

dispersion has the major contribution (60%) toward the total lattice energy rather than the Coulombic (25%) and polarization (15%) contribution. In the case of N−H···S dimer, the Coulombic (∼47%) and polarization (∼37%) are more important than the contribution coming from dispersion (∼16%). For the remaining molecular pairs, the dispersion (∼64%) is more important than the other contributors like Coulombic (∼10%) and polarization (∼26%). In Figure 7, the interaction energy has been plotted with respect to the centroid−centroid distance for all the molecular pairs. It has been found that the N−H···S molecular pairs are coming in the dotted region wherein the range of centroid−centroid distances are 11.5 to 13.5 Å. Also in the same centroid−centroid range, there are some molecular pairs having less energetic stabilization (−2.5 to −9.0 kcal/mol). Some molecular pairs (involving π−π stacking and C−H···π hydrogen bond) with I



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contacts (involving F3 in A and F4 in B), the distance and angle being 3.079(4) Å, 98° and 3.013(3) Å, 97°, respectively, qualifying it as a type I contact (Figure 8a). Similarly, in the

Figure 7. Plot of the interaction energy of the molecular dimer with respect to the centroid−centroid distance. Figure 8. (a) Type I (trans-geometry) homo halogen···halogen interaction in SB2 (F···F) and (b) in SB3 (Cl···Cl) molecules.

high energetic stabilization (−18 to −26 kcal/mol) exist at the centroid−centroid distance between 4.5 to 5.5 Å. In between them, few are there that have energies in the range of −5.0 to −12.5 kcal/mol. It is noteworthy that in the crystal packing of SB2 and SB3, type I homo halogen···halogen contacts111,112 have been observed. Halogen···halogen interactions play an important role in a molecular self-assembly in the solid state and in bimolecular systems.113 The nature, strength and directionality of C(spx)−F···F interactions (where x is the order of hybridization) have been evaluated theoretically on all symmetry unique dimers present in CF4, C2F4, and C6F6 crystals and on CF4, CHF3, CH2F2, and CH3F model dimers in the literature.114 The nature of Cl···Cl interactions115,116 has been studied and investigated in detail by Desiraju in 1986117 and Price in 1994. 118 Desiraju has shown that short intermolecular Cl···Cl contacts occur very frequently in βstructure of chloro-aromatics. In hexachlorobenzene, Cl···Cl contacts, with a distance of 3.72 Å, result in the molecule being arranged along the linear ribbon. There were some important packing differences between the β and non-β forms for planar aromatics and that any in-plane interaction such as Cl···Cl in principle is used to steer a crystal structure into the 4 Å modification. Price demonstrated that the appearance of Cl···Cl intermolecular contacts, which are shorter than would be expected from the conventional isotropic van der Waals radius, is shown to be the most common in the crystal structures of fully or highly chlorinated hydrocarbons. Furthermore, intermolecular perturbation theory has revealed that the charge-transfer contributions in the interaction energy is negligible, electrostatic forces are weak, and the repulsive wall is anisotropic. Recent investigations on the nature of Cl···Cl interaction in molecular crystals based on the experimental119 and theoretical charge density analysis in 2-chloro-3-quinolinyl methanol, 2-chloro-3-hydroxypyridine, and 2-chloro-3-chloromethyl-8-methylquinoline have been performed using CRYSTAL06120 and solid-state density functional theory (DFT) calculations.121 These research groups have reported that the range of energies for Cl···Cl interactions (Eint) evaluated from the local potential and kinetic energy density at the Cl···Cl bond critical points, varies from 2 to 12 kJ/mol. In the case of SB2, molecules A and B interact among themselves via F···F

case of SB3, the corresponding Cl···Cl contacts (involving Cl1 with molecule A, the distance and angle being 3.806(4) Å, 99° and 3.792(3) Å, 93°, respectively (Figure 8b). In order to view the electrostatic regions, which correlate with the interactions between the like halogen atoms, we have also plotted the electrostatic potential (ESP) and the decomposed ESP [in the range of −0.02 au (red) to 0.02 au (blue)] on the Hirshfeld surface (Figure 9). The arrows indicate the region for the halogen···halogen contact. In order to obtain quantitative insights into the nature of strong and weak interactions from topological considerations, we have performed an in-depth analysis using the QTAIM approach. Table 4 lists all the relevant topological parameters obtained from the AIMALL calculation for the strong N−H···S hydrogen bond and other weak intermolecular interactions including C(sp2)−halogen···halogen−C(sp2) contacts and H··· H122−124 intermolecular interactions. For the strong N−H···S hydrogen bond, the electron density (ρb) and the Laplacian (∇2ρb) at the bond critical point were observed in the range of 0.167−0.170 e/Å3 and 1.203−1.208 e/Å5, respectively, and the individual bond dissociation energy was observed in the range of 3.6−4.5 kcal/mol (obtained from the local potential energy density (Vb) and kinetic energy density (Gb) , Figure 10 and Table 4). Between the molecular pairs SB2_IV and SB3_IV associated with weak C−H···π, C−H···O, and bifurcated C− H···F intermolecular interactions, the ρb value (0.072 e/Å3) at the bond critical point of the C42−H42···F2 interaction is high in comparison to the ρb values (0.060 and 0.051 e/Å3) at the BCPs of C15−H15···F1 and C21−H21···F1 interactions. Subsequently, the calculated bond dissociation energy (2.69/ 2.54 kcal/mol) is also greater for the C42−H42···F2 in SB2_IV (Figure 10). In Figure 11, BCPs for the C−H···N intermolecular interaction have been shown for all possible centrosymmetric C−H···N dimers present in the crystal packing. It has been observed that the electron densities (ρb) at the BCPs for the C−H···N interaction are in the range of 0.055−0.059 e/Å3. Because of the presence of a C−H···N interaction in these dimers, a consequence of which results in two aromatic hydrogen atoms coming closer to each other, the J



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Figure 9. ESP plotted on the Hirshfeld surface mapped from −0.02 au (red) to 0.02 au (blue) for the halogen···halogen contact of SB2 and SB3 (1st row). Decomposed ESP map plotted on the Hirshfeld surface showing the contribution of F···F and Cl···Cl contact (2nd row).

Table 4. Topological Parametersa at the Bond Critical Point (BCP) of Some Selected Intermolecular Interactions motifs SB2_I SB2_IV

SB2_VI SB2_VIII SB2_IX SB3_IV

SB3_VII SB3_VIII

SB3_IX SB3_X SB4_VII

interactions

d (Å)

Rij (Å)

ρBCP (e/Å3)

∇2ρBCP (e/Å5)

Vb (au)

Gb (au)

ε

DEV/DEG (kcal/mol)

N2−H2···S2 N6−H6···S1 C15−H15···F1 C21−H21···F1 C21−H21···O1 C20−H20···π (C6)

2.26 2.28 2.38 2.45 2.68 2.81

2.311 2.317 2.393 2.487 2.689 2.837

0.170 0.167 0.060 0.051 0.042 0.042

1.208 1.203 0.793 0.678 0.484 0.416

−0.014233 −0.013935 −0.006015 −0.005047 −0.003759 −0.002899

0.013384 0.013207 0.007120 0.006038 0.004388 0.003608

0.054809 0.058148 0.078144 0.117823 0.250954 0.813787

4.47/3.60 4.37/3.56 1.89/1.92 1.58/1.63 1.18/1.18 0.91/0.97

C30−H30···N5 H31···H31 C25−H25···F4 F4···F4 C5−H5···F3 F3···F3 C36−H36···F2 C42−H42···F2 C42−H42···O2 C41−H41···π(C23)

2.60 2.27 2.66 3.01 2.79 3.08 2.47 2.33 2.66 2.81

2.628 2.399 2.661 3.011 2.838 3.076 2.496 2.349 2.684 2.859

0.055 0.055 0.036 0.032 0.029 0.031 0.050 0.072 0.044 0.041

0.564 0.685 0.565 0.648 0.425 0.560 0.758 0.994 0.576 0.455

−0.003974 −0.004334 −0.004034 −0.004752 −0.002758 −0.004022 −0.005531 −0.008582 −0.004261 −0.002795

0.004919 0.005718 0.004949 0.005737 0.003586 0.004916 0.006695 0.009445 0.005118 0.003756

0.082416 0.864486 0.046871 0.031776 0.171540 0.087609 0.116197 0.061236 0.175697 0.686045

1.25/1.32 1.36/1.53 1.27/1.33 1.49/1.54 0.87/0.97 1.26/1.32 1.74/1.80 2.69/2.54 1.34/1.38 0.88/1.01

C30−H30···N5 H31···H31 C25−H25···Cl2 C39−H39···Cl2 Cl2···Cl2

2.57 2.00 3.20 3.00 3.79

2.584 2.072 3.228 3.047 3.793

0.059 0.082 0.025 0.033 0.032

0.611 1.029 0.270 0.392 0.355

−0.004250 −0.006663 −0.001595 −0.002335 −0.001934

0.005294 0.008667 0.002196 0.003201 0.002808

0.046625 0.345669 0.161490 0.142374 0.139036

1.33/1.43 2.09/2.33 0.50/0.59 0.73/0.86 0.61/0.76

C4−H4···Cl1 Cl1···Cl1 C24−H24···Cl1 C4−H4···Cl2 C9−H9···N1

3.23 3.81 2.64 2.97 2.86

3.256 3.807 2.674 3.023 2.911

0.023 0.031 0.055 0.037 0.036

0.253 0.339 0.749 0.483 0.385

−0.001474 −0.001845 −0.004793 −0.002882 −0.002647

0.002705 0.002047 0.006280 0.003946 0.003319

0.168735 0.027865 0.066955 0.138472 0.186664

0.46/0.73 0.58/0.55 1.50/1.69 0.90/1.06 0.83/0.89

d = crystallographic interacting distance, Rij = bond path distance, ρBCP = electron density, ∇2ρBCP = the Laplacian of the electron density, Vb = local potential energy, Gb = local kinetic energy, ε = the ellipticity at the bond critical point, DEv = −0.5Vb, and DEG = 0.429Gb. a

bond dissociation energies for the F···F contacts are high (1.49 kcal/mol) in comparison to the value for the Cl···Cl contacts (0.61 kcal/mol). A very recent database study on the occurrence of N−H···S hydrogen bonding ring motif R22(8) for 1,2,4-triazole-5-thiones derivatives125 has been investigated. The search was performed with the cutoff on the N(triazole)···S(thione) (donor··· acceptor) distance being 3.45 Å. This resulted in 77 structures being observed. The presence of a centrosymmetric N−H···S supramolecular synthon R22(8) in the crystal packing with specific geometrical constraints (dH···S, 2.0 to 2.3 Å; ∠N−H···S, 150° to 170°, and 3D coordinates determined, R factor =

Computational Study of the Formation of Short Centrosymmetric N–H

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