Understanding of the Weak Intermolecular Interactions Involving

Article pubs.acs.org/crystal

Understanding of the Weak Intermolecular Interactions Involving Halogens in Substituted N‑Benzylideneanilines: Insights from Structural and Computational Perspectives Gurpreet Kaur and Angshuman Roy Choudhury* Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, Knowledge City, S. A. S. Nagar, Manauli PO, Mohali, 140306 Punjab, India S Supporting Information *

ABSTRACT: The C−F group, which is found in a large number of small organic molecules and drugs available in the market, has still not been fully understood in terms of the strength and directionality of the interactions offered by this group in guiding the formation of crystal lattices. In this manuscript, we have tried to understand the role played by the C−F group, using a model system of N-benzylideneanilines, on which we have previously done a systematic study with fluorine as a substituent on both rings. The effect on the packing of these molecules by replacing one of the fluorine atoms by either Cl or Br has been comprehended in this manuscript. It was observed that the features of the difluorinated analogues remained intact when the noninteracting fluorine atom was replaced by Cl or Br, while with the replacement of the interacting fluorine by Cl or Br, completely different packing characteristics were found to be developed. To quantify the strength of the interactions offered by “organic fluorine”, stabilization energies of the dimers (which has been found to interact through the C−H···F hydrogen bond) have been calculated by Gaussian 09 at the MP2 level using a 6-31+G* basis set. These values were found to be between −0.3 and −6.0 kcal/mol. To study the topological properties of the interacting molecular pair, AIM calculations have also been done using AIM2000. In the studied dimers, the existence of bond critical points (BCPs) at the C−H···F hydrogen bond have always been seen and Laplacian at those BCPs has also been found to be positive, which is clearly an indication of a closed shell type of interaction between the C−H and F−C groups.

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INTRODUCTION

designed containing molecules, which do not have any strong hydrogen bond donor or acceptor groups. The interactions, which are not as robust as strong hydrogen bonds, are also capable of guiding the packing in the crystal lattice to some extent, though they are not immediately anticipated. Weak hydrogen bonds like C−H···X, where X = O, N, F, Cl, and Br, fall in this category. The interactions involving C−H···O or C−H··· N hydrogen bonds are relatively stronger and their strength in directing the molecules in the crystal lattice have been well understood.4 The intermolecular interactions involving a C−F group has been reported to be ambiguous and is less explored in the literature, both in the presence and in the absence of other

The noncovalent interactions are the most important guiding forces for molecular recognition, and they play vital roles in governing the packing of molecules in the crystal lattice.1 Therefore, the understanding of these intermolecular interactions is of paramount importance in designing a new crystalline architecture. These noncovalent intermolecular forces can be as strong as strong hydrogen bonds (O−H···O−, N−H···O−, F−H···F−, N−H···N, N−H···O, O−H···O, O−H···N, etc.) or as weak as van der Waals interactions (C−H···π, π···π, etc.). The packing of molecules, containing strong hydrogen bond donor and/or acceptor groups such as >CO, −NH2, −OH, −COOH, etc., are mainly directed by those functionalities.2 The highly directional and persistent nature of these interactions make them predictable while designing a new crystalline framework.3 But the problem arises, when a crystal has to be © XXXX American Chemical Society

Received: October 22, 2013 Revised: February 13, 2014

A

dx.doi.org/10.1021/cg401573d | Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

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of benzonitrile and fluorinated benzonitrile indicated that the weak directional nature of C−H···F hydrogen bonds have resulted in subtle structural variation, which in turn resulted into the increase in the melting points of m-fluorobenzonitrile (mp = 12.5 °C) and p-fluorobenzonitrile (mp 38.5 °C) compared to the melting points of benzonitrile (mp = −13 °C) and o-fluorobenzonitrile (mp = −13.7 °C).18 The structural analyses of fluorinated and multifluorinated derivatives of benzene have further emphasized that though the C−H···F−C interactions are weak, they hold similar directional features like well-established hydrogen bonds.19 The structural investigations on halogensubstituted benzanilides concluded that the combined effect of strong hydrogen bonds, weak intermolecular interactions like C−H···F hydrogen bonds, and X···X (X = F, Cl, Br, and I) contacts have significant influence in altering the modes of packing depending on the position (ortho-, meta-, and para-) and nature (F, Cl, Br, and I) of halogen substitutions.20 Further studies on multihalogenated benzanilides21a and trifluoromethylated benzanilides21b have emphasized the fact that the presence of one or more C−F group(s) can alter the packing of molecules containing strong hydrogen bond donor and acceptor sites (−CONH− group). A recent tutorial review,22a a highlight,22b and a perspective22c have also underlined the significance of “organic fluorine” in the solid state chemistry. A number of different types of interactions involving the C−F group have been summarized by Berger et al., in their review. The present understanding of the influence of weak interactions in directing the packing of small organic molecules in the presence or absence of strong hydrogen bond donors and acceptors is becoming clearer with the results published in the last couple of years.23 So, now the current focus is to explore how one can utilize these weak interactions involving the C−F group in crystal engineering and supramolecular chemistry, as the prediction of crystal structure by the application of crystal engineering is still nontrivial. This implies that, still there is a lot more to explore in the field of weak noncovalent interactions, as there is no certainty on the robustness and repetitiveness of the supramolecular synthons generated by very weak hydrogen bond donors and acceptors in the crystal lattice. In order to achieve better understanding of the nature and role of the organic halogen (C−X, where X = F, Cl, and Br) group in directing crystal packing, one needs to carry out different systematic studies on various systems, in which the molecules are majorly packed via very weak hydrogen bonds offered by the said C−X group(s) and other weaker interactions and need to analyze the strength, directionality, and consistency of the synthons offered by them. Therefore our aim is to study the weak interactions offered by C−X (X = F, Cl, and Br) group(s) in order to understand the effectiveness of the supramolecular synthons formed by the weak hydrogen bonds (involving the halogen atom) and their repetitiveness in building the crystal lattice in the same system but with different substituents. To understand the behavior of aromatic C−X (where X = F, Cl, and Br) group(s), we have focused on two marginally different molecular frameworks based on N-benzylideneanilines and azobenzenes. We have recently reported the structural investigations on a series of fluorine substituted N-benzylideneanilines24a and halogenated azobenzenes24b using single crystal and powder X-ray diffraction supported by ab initio computational methods. In the current study, we have extended our earlier results in another series of halogen (F, Cl, and Br) substituted N-benzylideneanilines (Scheme 1), which provide us the opportunity to study the role of very weak hydrogen bonds and other weaker interactions (such as

stronger interactions. A number of research groups have expressed their controversial views regarding C−H···X, where X = F, Cl, and Br interactions. On the basis of the limited number of fluorinated compounds available in the Cambridge Structural Database5 (CSD), Shimoni and Glusker had pointed out in 1994 that the X−H···F−C (X = C, N, O) interactions are weak compared to CO···H−X interactions, but their contribution to crystal packing cannot be ignored.6 Howard et al. in 1996 commented on the weak acceptor abilities of the C−F group based on the database and computational studies.7 They concluded that the short contacts of the type C−H···X were rare. They also pointed out from theoretical calculations that the C(sp3)−F is a better hydrogen bond acceptor than C(sp2)−F. Furthermore, Dunitz and Taylor, based on their combined CSD and ab initio calculations, concluded that “organic fluorine hardly ever accepts hydrogen bonds”.8 This conclusion was based on the notion that a covalently bound fluorine has low proton affinity and is also unable to modify it by intramolecular electron delocalization and intermolecular “cooperative effects”. Dunitz once again emphasized9 that organic fluorine is incapable of providing stability by dimer formation in his study on fluorinated and perfluorinated hydrocarbons using PIXEL10 calculations. Thalladi et al., in 1998 for the first time, revealed the importance of “organic fluorine” in crystal packing, while investigating the structures of a number of fluorinated liquids using the newly developed technique of in situ crystallization.11 The authors also concluded that the C−F group prefers to form C−H···F interactions rather than C−F···F contacts. This trend was found to be different for the heavier halogens analogues. In the past decade, a number of research groups have been extensively involved in the experimental and computational structural studies on fluorinated organic compounds and have indicated that C−H···F interactions may be termed as weak hydrogen bonds and can be used for building a supramolecular architecture involving these intermolecular interactions. It has been shown in the cases of a number of fluorinated tetrahydroisoquinolines that the presence of one or two C−F groups in a fairly large molecular framework is capable of generating various supramolecular synthons through weak C−H···F interactions although the rational for those synthons were not achieved.12 The chloro and bromo analogues of these tetrahydroisoquinolines were found to pack differently, involving mostly C−O···X (X = Cl and Br) and other weaker interactions.13 Alonso et al. classified C−H···F−C interactions as weak hydrogen bonds through their experimental rotational spectroscopic studies supported by ab initio computational results.14 The importance of fluorine in generating specific supramolecular assemblies through C−H···F hydrogen bonds and C−F···F and C−F···π interactions in various different chemicals and biological systems was understood through a tutorial review in 2004.15 It was pointed out that the replacement of H by F has a significant influence in the crystal structure and also on chemical and physical properties of various small organic molecules. The cooperative nature of C−H···F hydrogen bonds with C−H···N and N−H···F hydrogen bonds has been shown in the cases of in situ crystallization of 2-fluoroaniline and 4fluoroaniline.16 It is noteworthy that the crystal structure of 3fluoroaniline is still not known. D’Oria and Novoa in 2008 have shown from their CSD analysis and ab initio calculations that the nature of C−H···F interactions involving two neutral fragments were different than in the cases where either or both the fragments were charged.17 They also classified these interactions as hydrogen bonds, except for the cases where both the fragments carry charges of the same sign. The systematic structural analyses B



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data were recorded on a Rigaku Ultimia IV diffractometer using parallel beam geometry with Cu Kα radiation. The observed PXRD patterns have been compared (using WINPLOTR26) with the simulated PXRD patterns generated from the crystal coordinates using Mercury27 (Figure S3 of the Supporting Information: 1 to 28). Melting points (Table S1 of the Supporting Information) were recorded and the DSC traces for all the solid compounds are given in Figure S4 of the Supporting Information (1 to 36). The labeling of atoms is shown as thermal ellipsoid plots drawn at 50% probability for the non-H atoms using Mercury. (Figure S5 of the Supporting Information: 1 to 32).

Scheme 1

a

Note: The compounds containing both Cl and Br have been kept aside from this manuscript.

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C−X···X and C−X···π, where X = F, Cl, and Br) offered by various C−X (X = F, Cl, and Br) groups present at different positions in the aromatic rings. The first nine compounds belonging to this series were reported by us earlier.23a A detailed description of the structural reports of the similar compounds deposited in the Cambridge Structural Database (CSD)25 have also been included in our earlier publication23a and, hence, they are not being discussed further. We have earlier observed that the change in the position of the fluorine atom resulted in entirely different packing characteristics of the molecules in the cases of fluorine substituted N-benzylideneanilines. We also pointed out that the C−H···F hydrogen bonds showed significant directionality (∠C−H···F > 160°). In the current manuscript, we aim to present the various types of supramolecular motifs offered by fluorine, chlorine, and bromine in identical chemical environments and wish to determine the strengths and the directionality of these intermolecular forces in the crystal lattices.

THEORETICAL CALCULATIONS

The * indicates the compounds which are found to be liquids at 25 °C.

Due to unavailability of the strong hydrogen bonding sites in our current system studied, the only interactions that are found to be present in the crystal structures are either weak hydrogen bonds or the van der Waals interactions. Out of all these interactions observed in the crystal structures we studied, our main interest was to look for the role played by the C−H···X (X = F, Cl, and Br) hydrogen bonds and C−X···X (X = F, Cl, and Br) interactions in the crystal packing of these compounds. Therefore, the stabilization energies of only those dimers, which were found to interact through these interactions, have been computed using Gaussian 09.28 Gauss View29 has been used as a graphical interface for Gaussian 09. The coordinates of such dimers were taken from their respective crystal structures and were used for the calculation of the stabilization energy provided by them without further optimization. If a dimer formed by two molecules was found to have more than one type of interaction (say one C−H···X and one C−H···π) then the halogen atom was exchanged by a H atom (placed at 0.95 Å from the C atom to which the halogen was bonded) to remove the contribution of the stabilization energy contributed by the interaction mediated by the halogen atom. Then the stabilization energy of the dimer was recalculated to determine the contribution of the other interaction (say C−H···π) in the total stabilization energy and thereafter the contribution from the C−H···X interaction was calculated by taking the difference of both energies. All calculations were performed by using Gaussian09 at the second order Møller−Plesset perturbation method (MP2)30 with the 6-31+G(*) basis set. The energies obtained for these dimers were corrected for the basis set superposition error (BSSE) by using the counterpoise method.31 To study the topological properties of the electron density, the wave function files (.wfn) for all the dimers were also generated by giving a command (output = wfn) in the input file for the single point energy calculation. From these wave function files, the topology of electron density distribution can be analyzed by Bader’s quantum theory32 of atoms in the molecule. AIM200033 was used to compute the bond paths and bond critical points between the interacting atoms. (3, −1) Bond critical points (BCPs) were found for each C−H···F short contacts encountered in the various structures reported here. The topological properties, namely electron density (ρ), and the Laplacian of the electron density (∇2ρ) at the (3, −1) BCPs are listed in the Tables containing the geometrical parameters of the intermolecular interactions. The positive sign of the Laplacian at all the BCPs found between the interacting H and F atoms is an indication of closed shell type interaction (like the hydrogen bond).

All the synthesized compounds were characterized by 1H NMR (400 MHz, Bruker Biospin Advance-III NMR spectrometer) (Figures S1 of the Supporting Information: 1 to 36) and FTIR (Bruker Tensor 72, equipped with diamond cell ATR) (Figure S2 of the Supporting Information: 1 to 36] spectroscopy. Powder X-ray Diffraction (PXRD)

RESULTS AND DISCUSSION In this mauscript, we are reporting the structures of 32 new compouds and we intend to present a vivid structural comparison of the new compounds with those reported earlier.23a For the

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EXPERIMENTAL SECTION

Procedure for the synthesis of all the compounds has been given in the Supporting Information. Scheme 1 describes all the molecules synthesized and the method of nomenclature used in this manuscript. Out of 36 synthesized compounds, 27 compounds were found to be solids at room temperature (25 °C), while the remaining nine compounds [compound nos. (C.N.) 20, 27, 29, 30, 38, 44, 45, 47, and 48] were found to be liquids. Compound 16, 18, 36, and 22 were found to exhibit polymorphism. C.N.

X1

X2

C.N.

X1

X2

C.N.

X1

X2

1 2 3 C.N.

p-F p-F p-F X1

p-F m-F o-F X2

4 5 6 C.N.

m-F m-F m-F X1

p-F m-F o-F X2

7 8 9 C.N.

o-F o-F o-F X1

p-F m-F o-F X2

16 17 18 C.N.

p-Br p-Br p-Br X1

p-F m-F o-F X2

19 20* 21 C.N.

m-Br m-Br m-Br X1

p-F m-F o-F X2

22 23* 24 C.N.

o-Br o-Br o-Br X1

p-F m-F o-F X2

25 26 27* C.N.

p-F p-F p-F X1

p-Br m-Br o-Br X2

28 29* 30* C.N.

m-F m-F m-F X1

p-Br m-Br o-Br X2

31 32 33 C.N.

o-F o-F o-F X1

p-Br m-Br o-Br X2

34 35 36 C.N.

p-Cl p-Cl p-Cl X1

p-F m-F o-F X2

37 38* 39 C.N.

m-Cl m-Cl m-Cl X1

p-F m-F o-F X2

40 41 42 C.N.

o-Cl o-Cl o-Cl X1

p-F m-F o-F X2

43 44* 45*

p-F p-F p-F

p-Cl m-Cl o-Cl

46 47* 48*

m-F m-F m-F

p-Cl m-Cl o-Cl

49 50 51

o-F o-F o-F

p-Cl m-Cl o-Cl

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C



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Table 1. Details of Intermolecular Interactions, Computed Stabiliztion Energies, and Topological Parameters of Compounds 1, 43, 25, 34, 16F2, and 16F1 code 1 43 25

34 16F1 16F2

C−D···A (D = H, F, Cl, Br; A = F, Cl, Br)

d(D···A) (Å)

θ (∠C−D···A) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2 ρ (e Å−5)

C6−H6···F2 C12−H12···F1 C13−H13···F2 C26−H26···F1 C11−Cl1···Cl1 C11−Br1···F1 C11−Br2···F2 C11−Br3···F3 C32−H32···N1 C17−H17···N1 C23−H23···N3 C12−H12···F1 C4−H4···Cl1 C12−H12···F1 C5−Br1···Br1 C1−H1···F1 C14−H14···F2 C23−H23···Br1

2.67 2.69 2.44 2.51 3.45 3.15 3.07 3.07 2.75 2.75 2.69 2.56 2.99 2.57 3.63 2.68 2.68 2.91

131 130 150 143 124 161 166 170 150 157 145 153 166 153 143 153 155 147

x, y + 1, z + 1 x − 1, y − 1, z − 1 x, y, z 1 − x, y + 1, 1 + z 1 − x, −y + 1, −z −1 + x, y, −1 + z −1 + x, y, −1 + z 1 + x, y, 1 + z x − 1, 1/2 − y, z − 1/2 −x + 1, y + 1/2, −z + 1/2 −x + 1, −y + 1, −z + 1 1 − x, − 1/2 + y, 1/2 − z −x, −y, −z −x + 1, y + 1/2, −z + 1/2 −x, −y + 1, −z x + 1/2, −y + 1/2, z x − 1/2, −y + 3/2, z x + 1/2, −y + 3/2, z

−1.10 −1.12 −2.50 −2.22 −0.66 −0.34 −0.30 −0.44 −4.63 −4.72 −4.49 −1.01 −1.46 −1.05 −0.51 −1.51 −1.49 −0.08

0.027 0.027 0.047 0.041 0.054 0.041 0.047 0.047 0.041 0.034 0.041 0.035 0.034 0.034 0.047 0.027 0.027 0.034

0.555 0.555 0.893 0.772 0.724 0.748 0.797 0.869 0.555 0.531 0.603 0.694 0.700 0.676 0.531 0.531 0.555 0.531

Structural Comparison of the Compounds Belonging to Classes 1a and 4a. The compound 1, having F at the para position of both rings, crystallizes in the centrosymmetric triclinic P1̅ space group with Z = 2. The packing of molecules of 1 in the crystal structure elucidates the formation of molecular sheets through the C−H···F hydrogen bonds involving both F atoms (F1 and F2) (Table 1 and Figure 1a). The replacement of the F atom in the B ring by Cl and Br (i.e., in 43 and 25, respectively) results in the formation of entirely different supramolecular motifs in the crystal lattice. In 43, type I C−Cl···Cl−C interactions along with weak C−H···F and C−H···Cl hydrogen bonds have been found to generate a hexameric network as shown in Figure 1b. In the case of 25, we encountered a monoclinic structure with Z′ = 3, and we observed that the molecules pack majorly by C−H···N hydrogen bonds and type I interhalogen C−F···Br−C interactions (Figure 1c). Among the compounds belonging to the subclass 4a (1, 34, 16), where the F atom on the A ring has been replaced by Cl and Br, respectively, 16 exists in two polymorphic forms (namely 16F1 and 16F2). Both 16F1 and 34 crystallize in the monoclinic centrosymmetric P21/c space group with Z = 4 and are isostructural. By the utilization of C−H···F hydrogen bonds involving H12 with F1, zigzag molecular chains were fashioned in such a way as were found in the case of 1. The replacement of F in the A ring by Cl and Br has resulted in the interconnection of the pair of antiparallel chains, through the C−H···Cl hydrogen bonds in the case of 34 and by type I C−Br···Br−C interactions in the case of 16F1 (Table 1 and Figure 1, panels d and e). The homohalogen interactions found in 16F1 are in contrast to the observation made by Nayak et al.20 in the cases of fluorinated benzenanilides, in which preference for type II geometry for homo/hetero halogen short contacts involving heavier halogens (Br and Cl) in the solid state have been revealed. It is interesting to note that the structure of 16F2 consists of an entirely different kind of molecular network via the C−H···F hydrogen bond involving the imine proton and the C−H···Br hydrogen bond (Figure 1f), thereby crystallizing in the orthorhombic Pna21 space group with Z = 8 and Z′ = 2. All the compounds described above displayed several different weak C−H···π interactions as well (Table S1 of the Supporting Information).

convenience of readers and for a better understanding, we would like to subdivide all the compounds into various groups such that the halogen substitution in one ring is kept constant and the same is varied in the other ring. In the discussion below, we will use “A” as an abberviation for the phenyl ring originating from benzaldehyde and “B” for the phenyl ring originating from aniline. An in depth structural description of all these compounds along with their figures can be found in the Supporting Information. A few representative figures and the Tables for weak interactions have been included in the following segment for the purpose of the discussion. Class 1: when F is at the para position of the A ring and (1a) the para position of the B ring is substituted by F, Cl, and Br (1, 43, 25), (1b) the meta position of the B ring is substituted by F, Cl, and Br (2, 44, 26), and (1c) the ortho position of the B ring is substituted by F, Cl, and Br (3, 45, 27). Class 2: when F is at the meta position of the A ring, (2a) the para position of the B ring is substituted by F, Cl, and Br (4, 46, 28), (2b) the meta position of the B ring is substituted by F, Cl, and Br (5, 47, 29), and (2c) the ortho position of the B ring is substituted by F, Cl, and Br (6, 48, 30). Class 3: when F is at the ortho position of the A ring, (3a) the para position of the B ring is substituted by F, Cl, and Br (7, 49, 31), (3b) the meta position of the B ring is substituted by F, Cl, and Br (8, 50, 32), and (3c) the ortho position of the B ring is substituted by F, Cl, and Br (9, 51, 33). Class 4: when F is at the para position of the B ring, (4a) the para position of the A ring is substituted by F, Cl, and Br (1, 34, 16), (4b) the meta position of A ring is substituted by F, Cl, and Br (4, 37, 19), and (4c) the ortho position of the A ring is substituted by F, Cl, and Br (7, 40, 22). Class 5: when F is at the meta position of the B ring, (5a) the para position of the A ring is substituted by F, Cl, and Br. (2, 35, 17), (5b) the meta position of the A ring is substituted by F, Cl, and Br (5, 38, 20), and (5c) the ortho position of the A ring is substituted by F, Cl, and Br (8, 41, 23). Class 6: when F is at the ortho position of the B ring, (6a) the para position of the A ring is substituted by F, Cl, and Br. (3, 36, 18), (6b) the meta position of the A ring is substituted by F, Cl, and Br (6, 39, 21), and (6c) the ortho position of the A ring is substituted by F, Cl, and Br (9, 42, 24). D



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Figure 1. (a) Sheet formation in 1 via weak C−H···F hydrogen bonds, (b) formation of hexameric unit in 43 by C−H···F, C−H···Cl hydrogen bonds, and type I C−Cl···Cl interactions, (c) chains of dimers through C−H···π and type I C−F···Br interactions, between three molecules of the asymmetric unit of 25 along the b and c axes, respectively, (d) formation of zigzag chains through weak C−H···F and their interconnection via weak C−H···Cl hydrogen bonds in 34, (e) zigzag chains formation through weak C−H···F hydrogen bonds, which further interact by type I C−Br···Br interaction in 16F1, and (f) molecular network, which is found to form by weak C−H···F and C−H···Br hydrogen bonds in 16F2.

were found to be between 1.0 and 2.5 kcal/mol in the cases of compounds 1, 43, 34, 16F1, and 16F2, while for C−H···N hydrogen bonds, it lies in the range of 4−5 kcal/mol. The AIM calculations indicated the existence of BCPs in all the cases of C−H···F hydrogen bonds and C−X1···X2 interactions with very

Various molecular networks formed by these C−H···π interactions have been described in the Figure S1 (panels a−h) of the Supporting Information. The stabilization energies calculated by using Gaussian 09 for the molecular dimers formed by weak C−H···F hydrogen bonds E



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Table 2. Details of Intermolecular Interactions, Computed Stabiliztion Energies and Topological Parameters of Compounds 2, 44, 26, 35, and 17 code

C−D···A (D = H, Cl, Br; A = F, Cl, Br)

d(D···A) (Å)

θ (∠C−D···A) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

2

C6−H6···F1 C11−H11···F2 C13−H13···F2 C11−H11···F1 C10−Cl1···F1 C11−H11···F1 C10−Br1···F1 C1−H1···F1 C9−H9···F1 C11−H11···Cl1 C1−H1···F1 C9−H9···F1 C11−H11···Br1

2.52 2.55 2.55 2.52 3.13 2.63 3.14 2.56 2.76 2.89 2.58 2.66 2.97

128 134 161 164 160, 113 166 162, 114 153 156 168 155 162 170

−x + 1, −y, −z + 1 −x, 1 − y, −z x, −y − 1/2, z − 1/2 x − 1, −y + 3/2, z − 1/2 −1 + x, y, z x − 1, −y + 1/2, z − 1/2 1 + x, y, z −x + 1, −y + 1, −z + 1 −x + 1, −y + 1, −z + 1 1 + x, −y + 1/2, 1/2 + z −x + 1, −y + 1, −z + 1 −x + 1, −y + 1, −z + 1 x, −y + 1/2, z − 1/2

−1.32 −1.57 −0.50 −1.20 −0.41 −1.23 −0.63 −3.31

0.039 0.038 0.036 0.036 0.041 0.027 0.047 0.036 0.023 0.041 0.034 0.030 0.041

0.758 0.695 0.707 0.710 0.797 0.548 0.821 0.678 0.471 0.579 0.659 0.589 0.555

44 26 35

17

low values of electron densities (ρ) and Laplacians (∇2ρ). These values are in agreement with the values reported from experimental charge density analysis for weak C−H···O hydrogen bonds and weak interactions, as reported by Munshi and Guru Row earlier.34 In this particular set of compounds, it has been found that the replacement of F in the A ring by the heavier halogens have completely altered the crystal packing, while the same kind of replacement in the B ring has kept some features of the difluorinated compound (i.e., formation of molecular chains involving H12 with F1) unaffected, as described above. Structural Comparison of the Compounds Belonging to Classes 1b and 5a. Compound 2 crystallizes in the monoclinic centrosymmetric P21/c space group. C−H···F hydrogen bonds are involved in forming head-to-head and tailto-tail dimers across the inversion centers, thereby generating molecular layers (Table 2, and Figure 2a). These layers are further interacted with the neighboring layers by weak C−H···F hydrogen bonds and C−H···π interactions. The replacement of F on the A or B ring by Cl and Br has not brought any change in the space group. So, all the compounds belonging to the subclasses 1b and 5a crystallize in P21/c space group with Z′ = 1. Futher, the compounds 44 and 26 of class 1b are isostructural, but with different packing features in comparison to 2. In the cases of the structures of 44 and 26, the molecular chain formation occurs through a weak C−H···F hydrogen bond and these chains are further interconnected through type II C−F···X (X = Cl or Br) (in 44 and 26, respectively) hetero halogen interactions thus giving rise to a sheetlike structure in the ac plane (Table 2 and Figure 2, panels b and c). In the similar manner as 44 and 26, the compounds 35 and 17 are also isostructural and have no similarity in the packing characteristics with compound 2. In the crystal packing of both 35 and 17, molecules related by center of inversion are forming dimers involving H9 and H1 with F1 (Table 2 and Figure 2, panels d and e). The fluorine atoms involved in these dimers have been found to have bifurcated C−H···F hydrogen bonds. These dimers are further propagated along the c glide through C−H···X (X = Cl or Br) hydrogen bonds in the compounds 35 and 17, respectively (Table 2 and Figure 2, panels d and e). All the three structures belonging to the subgroup 1b have various weak C−H···π interactions present in their respective lattices (Table S2 and Figure S2, panels a−c, of the Supporting Information), while the weak C−H···π interactions have been replaced by weak C−H···X (X = Cl or Br) hydrogen bonds in the cases of 35 and 17 (Table 2 and Figure 2, panels d and e).

−1.05 −3.86 −2.44

The stabilization energies of the dimers (IEG09) formed by C−H···F hydrogen bonds in the cases of 44 and 26 are about −1.2 kcal/mol, which is nearly equal, but lesser than the energies of the dimers formed in the case of 2 (−1.3 and −1.6 kcal/mol), in which two C−H···F hydrogen bonds are involved between the molecules participating in the dimer formation. The stabilization energies of the dimers (IEG09) formed by the C−H···F hydrogen bonds in the cases of 35 and 17 are about −3.5 kcal/mol, which is much more than those observed earlier as four C−H···F hydrogen bonds have been found to involve between the two interacting molecules. The AIM calculations for these structures indicated the existence of BCPs in all the cases of C−H···X (X = F, Cl, or Br) hydrogen bonds and C−X1···X2 interactions with very low values of electron densities (ρ) and Laplacians (∇2ρ) as seen earlier, indicating the weak closed shell nature of these interactions. In the case of structures belonging to the group 1b, it has been found that the replacement of F in the A ring by the heavier halogens have inroduced different packing features by the introduction of interhalogen contacts (Figure 2, panels a, b, and c), while the same kind of replacement in the B ring has generated different packing characteristics by the introduction of weak C−H···X (X = Cl or Br) hydrogen bonds (Figure 2, panels a, d, and e). It is also noteworthy that change in the crystal packing as well as in the interaction energies involving C−H···F hydrogen bonds have not been seen just by the interchange of Cl with Br or vice versa (Table 2 and Figure 2, panel b, vs panels c and d vs panel e). Structural Comparison of the Compounds Belonging to Classes 1c and 6a. Compound 3 crystallizes in the monoclinic noncentrosymmetric P21 space group with Z′ = 2, and the molecules within the asymmetric unit are interconnected via weak C−H···π interactions (Table S3 of the Supporting Information). Both the molecules present in the asymmetric unit form molecular chains through short, highly directional, and significantly stabilizing C−H···F hydrogen bonds involving the imine hydrogen H1 with F1 and H14 with F4, respectively (Table 3 and Figure 3, panels a and b). In one of the molecules of the asymmetric unit, these chains are further connected by another C−H···F hydrogen bond (Table 3 and Figure 3a). The other compounds belonging to the group 1c (45 and 27) were found to be liquids at ambient conditions. The DSC data on 45 and 27 did not indicate any sharp solidification or melting features. Several trials of crystal growth using in situ crystallization technique had failed to grow single crystals F



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Figure 2. (a) Propagating dimers in 2, which are further interconnected through C−H···F hydrogen bonds, (b) formation of molecular sheets by the combination of C−H···F hydrogen bond and type II C−F···Cl inteactions in 44, (c) molecular sheets formed by the utilization of the C−H···F hydrogen bond and type II C−F···Br inteactions in 26, (d) propagating dimers formed by C−H···F and C−H···Cl hydrogen bonds in 35, and (e) formation of dimers and their propagation in the lattice through C−H···F and C−H···Br hydrogen bonds, respectively, in 17.

Table 3. Details of Intermolecular Interactions, Computed Stabiliztion Energies and Topological Parameters of Compounds 3, 36F1, 36F2, 18F1, and 18F2 code 3

36F1 18F1 18F2

36F2

C−H···X

d(H···X) (Å)

θ (∠C−H···X) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

C1−H1···F2 C14−H14···F4 C10−H10···F1 C1−H1···F1 C1−H1···F1 C1−H1···F1 C14−H14···F2 C23−H23···F1 C1−H1···F1 C14−H14···F2

2.32 2.30 2.66 2.40 2.44 2.35 2.41 2.43 2.37 2.38

162 161 131 160 156 168 159 142 173 168

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

−4.76 −4.75 −0.68 −4.84 −4.97 −5.13 −5.14 −1.27 −4.98 −5.14

0.068 0.068 0.034 0.056 0.054 0.060 0.054 0.049 0.054 0.054

1.110 1.135 0.603 0.987 0.958 1.045 0.958 0.927 0.990 0.990

suitable for the structural analysis of these compounds. In the cases of 45 and 27, the replacement of F at the ortho position of

the B ring by Cl and Br, respectively, removed the possibilty of weak C−H···F hydrogen bonds involving the imine hydrogen, G



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Figure 3. (a) Formation of sheets in one of the molecule of the asymmetric unit of 3, (b) chain formation in second molecule of the asymmetric unit of 3, (c) formation of chains and their interconnection in 36F1 through C−H···F hydrogen bond and C−H···π interactions respectively, (d) ribbon formation through C−H···F hydrogen bond and their interlinkage via C−H···π interactions in 18F1, (e) chain formation through C−H···F hydrogen bond in both molecules of the asymmetric unit of 36F2, and (f) formation of a ladder-type structure through C−H···F hydrogen bonds in 18F2.

chains have been found to form through C−H···F hydrogen bonds (involving H1 with F1) along the b axis, and C−H···π interactions interconnect these chains along the c axis (Table 3, and Figure 3, panels c and d). Structures 3 and 18F2 were solved in the same space group P21, but with different unit cell dimensions, while the structure 36F2 was solved in the orthorhombic Pna21 space group. All these three structures (3, 36F2, and 18F2) have two molecules in

which was present in the case of 3, thereby lowering the melting point of 45 and 27. A similar trend was earlier observed by Vasylyeva and Merz in the cases of fluorinated benzonitriles.18 Among the compounds belonging to the subclass 6a (3, 36, and 18), compounds 36 and 18 exist as two polymorphs (36F1, 36F2, 18F1, and 18F2). Out of those, 36F1 and 18F1 crystallize in the orthorhombic noncentrosymmetric P212121 space group with Z = 4 and are isostructural. In the structures, 36F1 and 18F1 H



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Table 4. Details of Intermolecular Interactions, Computed Stabilization Energies, and Topological Parameters of Compounds 4, 46, 28, 37, and 19 code 4

46 28F1 28F2 37 19

C−D···A (D = H, Br, Cl; A = F, Cl, Br)

d (D···A) (Å)

θ (∠C− D···A) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

C13A−H13A···F3A C16A−H16A···F1A C18A−H18A···F3A C23A−H23A···F4A C5A−H5A···F1A C5A−H5A···F2A C5−H5···F1 C9−H9···F1 C5−H5···F1 C9−H9···F1 C4−H4···N1 C11−Br1···F1 C10−H10···F1 C6−Cl1···Cl1 C10−H10···F1 C6−Br1···Br1

2.59 2.62 2.53 2.56 2.56 2.70 2.62 2.70 2.65 2.65 2.70 3.15 2.62 3.56 2.63 3.60

160 157 135 140 136 128 136 156 138 156 172 166, 119 126 139 126 139

−x, −y, −z + 1 x, y, z − 1 −x, −y, −z + 1 −x, −y + 1, −z − 1 −x + 1, −y, −z + 2 x, y, z + 1 −x, y + 1/2, −z + 1 −x + 1, y + 1/2, −z + 1 −1 − x, −1/2 + y, 1 − z −x + 2, y − 1/2, −z + 1 −x + 1, y + 1/2, −z + 3/2 1/2 − x, 1 − y, −1/2 + z −x + 1, y + 1/2, −z + 3/2 2 − x, −y, 1 − z −x + 2, y − 1/2, −z + 3/2 −x + 1, −y + 2, −z + 2

−0.26 −0.59 −1.13 −1.41 −1.14 −1.08 −0.69 −1.33 −0.72 −1.42 −2.77 −0.83 −0.87 −0.11 −0.83 −0.28

0.032 0.031 0.040 0.035 0.037 0.026 0.034 0.023 0.031 0.026 0.041 0.047 0.031 0.034 0.031 0.047

0.642 0.606 0.770 0.690 0.715 0.543 0.659 0.480 0.616 0.536 0.579 0.797 0.623 0.507 0.618 0.555

observed in the crystal structures of both 46 and 28F1. Therefore, we consider these to be isostructural. The structure 28F2 was solved in the orthorhombic noncentrosymmetric P212121 space group and displays a completely different crystal packing involving the C−H···N hydrogen bond and weak type II C−F···Br interactions (Table 4 and Figure 4f). In a similar manner, ample variation in the crystal packing has been observed on the replacement of F on the A ring by Cl or Br (37 and 19). Both compounds 37 and 19 belonging to the subclass 4b crystallize in the monoclinic centrosymmetric P21/c space group with Z = 4. In the ab plane, molecular ribbonlike formation involving C−H···F hydrogen bonds has been seen (Table 4 and Figure 4, panels g and h) in the similar fashion as was observed in the cases of structures 34 and 16F1 (Table 1 and Figure 1, panels d and e). Then these molecular ribbons are interconnected through type I C−X···X (X = Cl or Br) interactions (Table 4 and Figure 4, panels g and h). Very weak C−H···π interactions in the ac plane have also been identified in between the sheets formed by C−H···F hydrogen bonds and C−X···X (X = Cl or Br) interactions (Table S4 and Figure S4, panels f and g, of the Supporting Information). The topological properties at the BCPs, have been calculated between the interacting pair of molecules. The values of ρ and Laplacian (∇2ρ) at the BCP have been found to be similar to the values observed in the cases of weak interactions observed and are reported in the Table 4. In this case also, the structural features observed in the case of 4, has not been carried by the compounds belonging to its group members, in which one of the fluorine was replaced by Cl or Br. Structural Comparison of the Compounds Belonging to Classes 2b and 5b. All the compounds belonging to the subclasses 2b (5, 47, 29) and 5b (5, 38, 20) exist as liquids at 25 °C. Among these, the crystal structure of 5 could be determined using the in situ crystallization technique, while crystals of the others could not be grown in the same way. The DSC data of the compounds 20 and 47 have not shown any indication of solidification in the cooling and heating cycles (25 °C to −100 °C and heated back to 25 °C) [Table S1 and Figure S4 (5 and 32) of the Supporting Information]. For the compounds 29 and 38, though some features were seen in their DSC traces [Table S1 and

the asymmetric unit. The common trend that is found in all the structures (3, 36F1, 36F2, 18F1, and 18F2), even with both the molecules of the asymmetric unit (3, 36F2, and 18F2), is that the F atom present in the ortho position of the B ring has been found to be involved in the formation of weak C−H···F hydrogen bonds involving the acidic imine hydrogen H1 (Table 3 and Figure 3, panels a, b, c, d, e, and f). The chains formed through this interaction interact with other chains, either formed by the set of same molecules (36F1, 18F1, and 18F2) or by the set of other molecule of the asymmetric unit (3 and 36F2) through C−H···π interactions. In the case of the structure 18F2, the molecules constituting the asymmetric unit are interacting through the C−H···F hydrogen bond. It is worth mentioning that the C−H···F hydrogen bonds involving the acidic imine hydrogen H1 have marginally higher values of electron density at their BCPs (0.054−0.068 e Å−3). Also, the values of the stabilization energies of the dimers interacting through this C−H···F hydrogen bond have been found to be much more (∼ 2 kcal/mol) than those observed in the earlier cases involving aromatic protons (Table 3). Structural Comparison of the Compounds Belonging to Classes 2a and 4b. Compound 4 crystallizes in the space group P1̅ with Z = 4 and Z′ = 2. This compound involves the formation of layer motifs through dimeric C−H···F hydrogen bonds, which further interlink with other layers by weak C−H···F hydrogen bonds (Table 4 and Figure 4a) and C−H···π interactions (Table S4 of the Supporting Information). The replacement of F on the B ring by Cl or Br has completely altered the crystal packings of 46 and 28 belonging to the subclass 2a. While, 46 exists in only one form, two different polymorphs are found for the compound 28, namely 28F1 and 28F2. The structures 46 and 28F1 were solved in the monoclinic noncentrosymmetric P21 space group with Z = 2 with similar unit cell dimensions and packing features in their crystal structures. Weak C−H···F hydrogen bonds (involving H5 with F1) lead to the formation of zigzag chains in the crystal structures of 46 and 28F1 (Table 4 and Figure 4, panels b and c). A chain of hetero dimers via combination of weak C−H···F hydrogen bond (involving H9 with F1) (Table 4 and Figure 4, panels d and e) and C−H···π interactions (Table S4 of the Supporting Information and Figure 4, panels d and e) has also been I



Article

Figure 4. (a) Formation of dimers and their interconnection through C−H···F hydrogen bonds in 4, (b) zigzag chains formation by C−H···F hydrogen bonds in 46, (c) formation of a similar kind of chains by C−H···F hydrogen bonds in 28 as was seen in 46, (d) propagating dimers in 46 formed via combination of C−H···F hydrogen bonds and C−H···π interactions, (e) C−H···F hydrogen bond and C−H···π interactions, which were found between the chains of heterodimers in 28F1, (f) formation of molecular chains through weak C−H···N hydrogen bonds and C−F···Br interactions in 28F1, (g) molecular sheet formation through weak C−H···F hydrogen bonds and C−Cl···Cl interactions in 37, and (h) C−H···F hydrogen bonds and C−Br···Br interactions, forming molecular sheets in 19. J



Article

Table 5. Details of Intermolecular Interactions, Computed Stabiliztion Energies, And Topological Parameters of Compounds 6, 39, and 21 code

C−D···F (D = H, Cl, Br)

d(D···F) (Å)

θ (∠C−D···F) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

6 39

C1−H1···F1 C1−H1···F1 C3−H3···F1 C6−Cl1···F1 C1−H1···F1 C3−H3···F1 C6−Br1···F1

2.47 2.46 2.66 3.02 2.49 2.64 3.05

163 153 149 133, 161 152 150 135, 161

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

−4.09 −4.92

0.041 0.048 0.027 0.054 0.045 0.029 0.054

0.768 0.864 0.558 0.966 0.823 0.594 0.966

21

−0.10 −5.30 −0.43

Figure 5. (a) Formation of molecular chains in 6 via weak C−H···F hydrogen bonds, (b) interconnection of the molecular chains formed in 6 through C−H···π interactions, (c) interconnecting molecular layers, which were formed by weak C−H···F hydrogen bonds, through quasi type I/type II C−F··· Cl interactions in 39, and (d) interconnecting molecular layers in 21, which were formed in a similar way as 39 through quasi type I/type II C−F···Br interactions.

determined as none could be crystallized when cooled from room temperature to −170 °C in a quartz capillary on the diffractometer using the Oxford cryosystem. All the compounds belonging to the subclass 6b (6, 21, 39), crystallize in the same space group P212121 with similar unit cell dimensions and having almost similar packing features. Molecular chains are formed through C−H···F hydrogen bonds involving imine hydrogen (i.e., H1) in compound 6 (Table 5, Figure 5a), while in the compounds 39 and 21, the F atom has been found to be bifurcated and form hydrogen bonds by involving both imine and aromatic hydrogen (H1 and H3, respectively). Futher, these chains are interlinked through quasi type I/type II interhalogen C−F···X (X = Cl or Br) interactions35

Figure S4 (14 and 23) of the Supporting Information], yet the compounds could not be crystallized in situ. Structural Comparison of the Compounds Belonging to Classes 2c and 6b. Among the compounds belonging to the subclass 2c (6, 30, 48), only 6 exists in the solid state at 25 °C, while others are liquids at the same temperature. Compound 6 packs in the lattice by utilizing C−H···F hydrogen bonds involving imine hydrogen (H1) and C−H···π interactions. When the F atom on the B ring (which is involved in the formation of C−H···F hydrogen bonds in 6) was replaced by Cl or Br, probably due to the absence of that particular C−H···F hydrogen bond, the compounds 30 and 48 exist as liquids as has been seen in the case of 3. Crystal structures of 48 and 30 could not be K



Article

Table 6. Details of Intermolecular Interactions, Computed Stabiliztion Energies, and Topological Parameters of Compounds 7, 49, 31, 40, and 22 code

C−H···X (X = F, Cl, Br)

d(H···X) (Å)

θ ∠C−H···X(deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

7

C6A−H6A···F1 C6A−H6A···F2 C1−H1···F1 C6−H6···Cl1 C6−H6···Br1 C12−H12···Cl1 C12−H12···Br1

2.61 2.54 2.32 2.99 3.07 2.99 3.08

127 136 146 130 134 136 133

−x + 2, −y, −z + 1 x, −y + 1/2, z + 1/2 −x + 1, 1 − y, −z x + 1, −y + 3/2, z + 1/2 x − 1, −y + 1/2, z − 1/2 x, −y + 1/2, z + 1/2 x, −y + 1/2, z + 1/2

−0.14 −0.62 −2.64 −0.71 −0.88 −0.68 −0.37

0.035 0.041 0.067 0.034 0.041 0.034 0.034

0.596 0.775 1.154 0.507 0.483 0.483 0.435

49 31 40 22

Figure 6. (a) C−H···F hydrogen bonds present in the crystal structure of 7, (b) formation of chains via weak C−H···Cl hydrogen bonds, which further interconnect through weak C−H···π interactions in 49, (c) chains formation and their interconnection via weak C−H···Br hydrogen bonds and weak C−H···π interactions, respectively, in 31, (d) formation of zigzag chains along the c axis through C−H···Cl hydrogen bonds in 40, and (e) molecular chain formation through C−H···Br hydrogen bonds in 22.

along the b axis (Table 5 and Figure 5, panels c and d) and via weak C−H···π interactions along the c axis in the compounds 39 and 21 (Table S5 of the Supporting Information and Figure 5a). But in the case of 6, the molecular chains formed are further propagating in the lattice only through C−H···π interactions (Table 5 and Figure 5b) and a similar C−F···F quasi type

I/type II interhalogen interaction has not been seen. Thus, it can be concluded that 39 and 21 are isostructural but different from 6. The C−H···F hydrogen bonds involving H1 have higher electron densities at their BCPs (∼0.048 e Å−3) as was also seen in the cases of compound 3, 36F1, 36F2, 18F1, and 18F2. Also, L



Article

Table 7. Details of Intermolecular Interactions, Computed Stabiliztion Energies, and Topological Parameters of Compounds 8, 50, 32, 41, and 23 code

C−D···A (D = H, Cl, Br; A = F)

d(D···A) (Å)

θ (∠C−D···A) (deg)

symmetry code

IEG09 (kcal/mol)

ρ (e Å−3)

∇2ρ (e Å−5)

8

C9−H9···F1 C1−H1···F1 C9−H9···F1 C1−H1···F1 C9−H9···F1 C1−H1···F1 C1−H1···F1B C9B−H9B···F1B C3−Cl1···F1B C5−H5···F1A C1−H1···F1B C9B−H9B···F1B C3−Br1···F1B C5−H5···F1A

2.55 2.67 2.61 2.69 2.66 2.70 2.61 2.56 3.30 2.57 2.66 2.55 3.31 2.62

169 157 164 155 163 154 167 125 120, 125 124 163 126 116, 123 124

−x + 1, y − 1/2, −z + 1/2 −x + 1, y − 1/2, −z + 1/2 −x + 2, y − 1/2, −z + 3/2 −x + 2, y + 1/2, −z + 3/2 −x + 2, y + 1/2, −z + 3/2 −x + 2, y − 1/2, −z + 3/2 −x + 1, y + 1/2, −z + 3/2 1 − x, y + 1/2, −z + 3/2 1 − x, y + 1/2, −z + 3/2 −x + 1/2, −y + 1, +z − 1/2 −x + 1, y − 1/2, −z + 3/2 −x + 1, y − 1/2, −z + 3/2 −x + 1, y − 1/2, −z + 3/2 −x + 3/2, −y + 1, z − 1/2

−4.82

0.038 0.030 0.032 0.027 0.029 0.026 0.028 0.043 0.039 0.043 0.025 0.043 0.047 0.029

0.734 0.584 0.628 0.546 0.570 0.531 0.575 0.797 0.756 0.797 0.521 0.801 0.676 0.716

50 32 41

23

−4.83 −5.27 −1.16

−1.20 −0.85

−1.35

Figure 7. (a) Formation of heterodimers in 8 via weak C−H···F hydrogen bonds, (b) weak C−H···F hydrogen bonds, which results in the formation of heterodimers in 50, (c) formation of heterodimers in 32 via weak C−H···F hydrogen bonds, (d) network formation through C−H···F hydrogen bonds in 41, and (e) C−H···F hydrogen bonds in 23, which form a similar kind of network as was found in 41.

the values of the stabilization energies of the dimers formed by this C−H···F hydrogen bond lie in the range between −4.09 and −5.30 kcal/mol. The C−H···F hydrogen bonds formed involving H3 in the case of the compounds 39 and 21 have lower values of electron densities at their BCPs (0.027 and 0.029 e Å−3), thus their contribution toward the sabilization energy of the dimers fomed by H1 and H3 with F1 must be lesser in comparison to the stabilization energy provided by the C−H···F hydrogen bond involving H1 with F1. Structural Comparison of the Compounds Belonging to Classes 3a and 4c. Compound 7 crystallizes in the monoclinic space group P21/c with Z = 2 (Z′ = 0.5). The molecule exhibits positional disorder around the CN bond with a 0.5 occupancy, which makes the molecule symmetrical and thus only half of the molecule is present in the asymmetric unit. The molecules of compound 7 pack in the crystal lattice by the utilization of dimeric C−H···F hydrogen bonds to form molecular sheets (Table 6 and Figure 6a), which further get interlocked through both C−H···F hydrogen bonds and C−H···π interactions (Table S6 and Figure S6a of the

Supporting Information), thereby generating different kinds of supramolecular motifs as reported by us earlier. The compounds belonging to the group 3a (7, 49, and 31) and group 4c (7, 40, 22) crystallizes in the same space group as 7. Unlike 7, none of the compounds belonging to the group 3a and 4c was disordered. Chains along the a axis are formed by weak C−H···Cl and C−H···Br hydrogen bonds, respectively, involving the same H atom (H6) (Table 6 and Figure 6, panels b and c) in 49 and 31, respectively. The chains thus formed are then held by weak C−H···π interactions in the crystal lattice in both the compounds (Table S6 and Figure S6, panels a and b, of the Supporting Information). Therefore, these are isostructural. Similarly, in the structures 40 and 22 of group 4c, zigzag chains are formed along the c axis through C−H···X (X = Cl or Br) hydrogen bonds involving the same H atom (H12) (Table 6 and Figure 6, panels d and e). It is noteworthy that unlike 7, C−H···F hydrogen bonds have not been found in the structures of 49, 31, 40, and 22. Rather, C− H···X (X = Cl or Br) hydrogen bonds play major contribution in the packing of molecules in the crystal lattice. Also, no M



Article

Table 8. Details of Intermolecular Interactions, Computed Stabiliztion Energies, And Topological Parameters of Compounds 9F1, 9F2, 51, 33, 42, and 24 code

C−H···X (X = N, F, Cl, Br)

d(H···X) (Å)

θ (∠C−H···X) (deg)

symmetry code

IEG09 kcal/mol

ρ (e Å−3)

∇2ρ (e Å−5)

9F1 9F2

C6−H6···F2 C5−H5···F2 C12−H12···F2 C4A−H4A···Cl1A C6A−H6A···Cl1A C6A−H6A···Br1A C11−H11···F1 C12−H12···N1 C9−H9···F1 C5−H5···F1 C6−H6···Cl1 C5−H5···F1 C6−H6···F1 C12−H12···F1

2.68 2.62 2.64 2.87 2.87 3.04 2.60 2.57 2.60 2.53 2.98 2.65 2.69 2.67

131 132 176 142 133 126 131 140 142 139 120 124 122 144

−x, −y + 1, −z + 1 −x + 1, y + 1/2, −z + 1/2 x −1/2, −y + 1/2, −z x + 1, y + 1, z −x + 1, −y + 2, −z + 1 −x, −y, 1 − z −x + 1, y + 1/2, −z + 1/2 −x + 1, y + 1/2, −z + 1/2 x − 1/2, y, −z + 1/2 x − 1/2, 1/2 − y, 1 − z x + 1/2, 1/2 − y, 1 − z 2 − x, y − 1/2, 3/2 − z −x + 2, y − 1/2, −z + 3/2 −x + 2, −y + 3, 1 − z

−6.12 −3.46 −1.91 −1.41 −4.28 −4.39 −0.83 −2.94 −0.95 −1.14 −1.46 −4.40

0.026 0.028 0.027 0.041 0.041 0.041 0.037 0.054 0.035 0.036 0.041 0.029 0.029 0.023

0.560 0.558 0.555 0.628 0.628 0.555 0.715 0.772 0.676 0.719 0.555 0.608 0.601 0.447

51 33 42

24

−1.72

and is also involved in the type I interhalogen C−F···X (X = Cl or Br) interactions in 41 and 23, respectively (Table 7 and Figure 7, panels d and e). The stabilization energies provided by the hetero dimers formed in the cases of 8, 50, and 32 are in the range between −4.8 and −5.3 kcal/mol. The stabilization energies of the dimers formed in the cases of 41 and 23 are much less than those found for 8, 50, and 32. The values of the electron densities and Laplacians found at the BCPs, which exist between C−H···F hydrogen bonds, belonging to these groups are nearly similar. Structural Comparison of the Compounds Belonging to Classes 3c and 6c. Among the compounds belonging to the group 3c (9, 51, 33), compound 9 exists as two polymorphs (9F1 and 9F2). The structures 9F1 and 51 were solved in the P21/c space group, while the structures 9F2 and 33 were solved in P212121 and Pbcn space groups, respectively. All the compounds of this group have positional disorder around the CN bond. Structures 9F1 and 9F2 were refined with 0.5 occupancy of both the parts, while in structures 33 and 51, the occupancy ratio of the two parts were found to be 0.91:0.09 and 0.55:0.45, respectively. Compound 9F2 pack through bifurcated C−H···F hydrogen bonds in the lattice (Table 8 and Figure 8b), while the rest of the compounds belonging to the group 3c form dimers in their respective crystal structure through C6−H6···X (X = F1 or Cl1 or Br1) hydrogen bonds (Table 8 and Figure 8, panels a, c, and d). Then, these dimers propagate in the lattice through C−H···Cl hydrogen bonds in the case of compound 51 (Table 8 and Figure 8c) and through C−H···π interactions in the case of 33 (Table S8 of the Supporting Information and Figure 8d), while in 9F1, no other interaction between the molecular dimer has been observed. Among the compounds belonging to the subclass 6c (9, 42, 24), no similarity has been observed in their crystal packing. Compound 42 crystallizes in the orthorhombic centrosymmetric Pbca space group with Z = 8. The molecules of 42 have been found to interact through the formation of two types of hetero dimers using weak C−H···F and C−H···N hydrogen bonds parallel to the b axis (Table 8 and Figure 8e) and by involving C−H···F and C−H···Cl hydrogen bonds parallel to the a axis (Table 8 and Figure 8f). Compound 24 crystallizes in the monoclinic centrosymmetric P21/c space group with Z = 4. The molecules related by the center of inversion interact through dimeric C−H···F hydrogen bonds. The dimers thus formed are

interhalogen interactions have been observed in the structures of the compound belonging to the group 3a and 4c. The stabilization energy offered by the C−H···F hydrogen bond (involving H1 wih F1) in 7 has been found to be much more than the stabilization provided by weak C−H···X (X = Cl or Br) hydrogen bonds in the compounds 49, 31, 40, and 22. The values of the electron density and Laplacian found at the BCPs of C−H···X (X = F, Cl, or Br) hydrogen bonds have almost similar values except for the C−H···F hydrogen bond involving H1 with F1, which is much more stabilizing, as discussed above. Structural Comparison of the Compounds Belonging to Classes 3b and 5c. Compounds belonging to the group 3b (8, 50, 32) have been found to crystallize in the monoclinic centrosymmetric P21/c space group with Z = 4. These compounds display similar structural features. In compound 8, the F atom on the para position of the B ring does not participate in any kind of interaction. Therefore, the replacement of that particular F by Cl or Br, has not brought any alteration in the crystal packing. All the compounds belonging to this group are involved in the formation of heterodimers by the use of weak C−H···F hydrogen bonds, involving H9 and H1 with F1 (Table 7a, Figure 7, panels a, b, and c). The molecular dimers thus formed are then interconnected again through C−H···F hydrogen bonds (involving F1, which is bifurcated in the crystal lattice) and thus propagating along the crystallographic b axis. However, the replacement of the F present at the orthoposition of the A ring by Cl or Br (41 and 23) has resulted into completely different crystal packing. All these three compounds exist as liquids at 30 °C. Compound 8 was crystallized by in situ crystallization technique, while the crystals of the compounds 23 and 41 were grown in a refrigerator maintained at −20 °C and those were mounted quickly in a cold room at about 20 °C and were transferred to the diffractometer with the Oxford cryosystem maintained at 0 °C. Structures 41 and 23 are solved in the orthorhombic noncentrosymmetric P212121 space group with Z = 4 and are isostructural. Both the structures 41 and 23, are disordered due to the rotation of the aryl ring around the N−C(Ar) bond. Therefore, the fluorine atom on the B ring has been found to be present at both the meta position of the B ring (F1A and F1B) with the occupancy of 0.5 at each position. Both the compounds involve the formation of linear chains through the C−H···F hydrogen bond (involving H5 with F1A) (Table 7 and Figure 7, panels d and e) in their crystal lattices. The atom F1B is trifurcated and forms hydrogen bonds with H1 and H9B N



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Figure 8. (a) Formation of molecular sheet of dimers formed via weak C−H···F hydrogen bonds in 9F1, (b) the packing of 9F2 in its crystal structure via bifurcated C−H···F hydrogen bonds, (c) formation of dimers and their propagation through weak C−H···Cl hydrogen bonds in 51, (d) molecular dimer formation and its propagation in the crystal lattice of 33 through weak C−H···Br hydrogen bonds and C−H···π interactions, respectively, (e) propagating dimers, which are formed by C−H···F and C−H···N hydrogen bonds along the b axis in 42, (f) formation of heterodimers and its extension in the crystal structure of 42 through combination of C−H···F and C−H···Cl hydrogen bonds and C−Cl···π interactions, and (g) trifurcated C−H···F hydrogen bonds, which interconnect the molecules in the crystal structure of 24.

Thus, in these set of compounds, much similarity in their crystal structures has not been observed. It has been found through Gaussian09 calculations that the stabilization energies provided by C6−H6···X (X = Cl1 or Br1) hydrogen bonds are nearly the same in the compounds 51 and 33, but lesser than that

further interlinked among themselves by another C−H···F hydrogen bond (Table 8 and Figure 8g). In this case, the F atom has been found to be trifurcated and the Br atom in the A ring does not involve in any kind of intermolecular interaction. None of these compounds have displayed any C−H···π interaction. O



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isostructural in general, while the corresponding fluorinated derivatives have displayed different types of packing characteristics, thereby yielding different crystal structures altogether. Only a few chloro- and bromo- analogues (43 and 25 and 42 and 24) did not show similarity in their interactions and the cystal packing as was observed in all the other cases. (2) We observed that some of the packing features of the difluoro- compounds (1−9) have been carried forward in the crystal packing of their corresponding chloro- and bromo- analogues in the eight compounds studied here. The first example of this feature has been observed in the cases where the fluorine atom is present at the para- position on the B ring, and either Cl or Br is present at the para- or meta- position on the A ring (classes 4a and 4b). In these cases, the formation of the same type of zigzag chains through C−H···F hydrogen bonds involving the para-F on the B ring (1, 34, 16, 37, and 19) (Figure 1, panels a, d, e, Figure 4, panels g, and h) have been observed. Further, in the cases of 3, 18, 36, 6, 21, and 39, where F is present in the orthoposition on the B ring and F/Cl/Br is present at the para- or meta- positions on the A ring, the structures of those compounds have been majorly influenced by the intermolecular C−H···F hydrogen bond (with stabilization energy in the range of 4−5 kcal/mol), involving the imine hydrogen and the o-F of the B ring. It is noteworthy that the halogen atom present on the A ring generally did not participate in any of the intermolecular interactions (Figure 3, panels a, b, c, d, e, and f, and Figure 5, panels a, b, c, and d). (3) The robustness of the synthons found in 3, 6, and 8 was experienced when the noninteracting fluorine was replaced by Cl or Br in the cases of compounds belonging to the class 3b (8, 32, and 50) (Figure 7, panels a, b, and c), the class 6a (3, 36, and 18) (Figure 3, panels b, c, d, e, and f) and the class 6b (6, 21, and 39) (Figure 5, panels a, c, and d). (4) On the other hand, when the interacting fluorine is replaced by Cl or Br, the possibility of the robust synthon found in 3 and 6 was removed, due to which the resulting compounds (27, 30, 45, and 48) were found to be liquids at ambient conditions. (5) Further, it is to be noted that the dimers formed through C−H···F hydrogen bonds involving the imine H have higher stabilization energies (4−5 kcal/mol) than those involving aromatic protons (

Understanding of the Weak Intermolecular Interactions Involving

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