Understanding of the Weak Intermolecular Interactions InvolvingHalogens in Substituted N‑Benzylideneanilines: Insights fromStructural and Computational PerspectivesGurpreet 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 guidingthe formation of crystal lattices. In this manuscript, we have tried to understand the role played by the C−F group, using a modelsystem of N-benzylideneanilines, on which we have previously done a systematic study with fluorine as a substituent on bothrings. The effect on the packing of these molecules by replacing one of the fluorine atoms by either Cl or Br has beencomprehended in this manuscript. It was observed that the features of the difluorinated analogues remained intact when thenoninteracting 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 −0.3and −6.0 kcal/mol. To study the topological properties of the interacting molecular pair, AIM calculations have also been doneusing AIM2000. In the studied dimers, the existence of bond critical points (BCPs) at the C−H···F hydrogen bond have alwaysbeen seen and Laplacian at those BCPs has also been found to be positive, which is clearly an indication of a closed shell type ofinteraction between the C−H and F−C groups.
■ INTRODUCTION
The noncovalent interactions are the most important guidingforces for molecular recognition, and they play vital roles ingoverning the packing of molecules in the crystal lattice.1
Therefore, the understanding of these intermolecular inter-actions is of paramount importance in designing a new crystallinearchitecture. These noncovalent intermolecular forces can beas 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 asweak as van der Waals interactions (C−H···π, π···π, etc.). Thepacking of molecules, containing strong hydrogen bond donorand/or acceptor groups such as >CO, −NH2, −OH,−COOH, etc., are mainly directed by those functionalities.2
The highly directional and persistent nature of these interactionsmake them predictable while designing a new crystallineframework.3 But the problem arises, when a crystal has to be
designed containing molecules, which do not have any stronghydrogen bond donor or acceptor groups. The interactions,which are not as robust as strong hydrogen bonds, are alsocapable of guiding the packing in the crystal lattice to someextent, though they are not immediately anticipated. Weakhydrogen bonds like C−H···X, where X = O, N, F, Cl, and Br, fallin this category. The interactions involving C−H···O or C−H···N hydrogen bonds are relatively stronger and their strength indirecting the molecules in the crystal lattice have been wellunderstood.4 The intermolecular interactions involving a C−Fgroup has been reported to be ambiguous and is less explored inthe literature, both in the presence and in the absence of other
Received: October 22, 2013Revised: February 13, 2014
stronger interactions. A number of research groups have ex-pressed their controversial views regarding C−H···X, where X =F, Cl, and Br interactions. On the basis of the limited number offluorinated compounds available in the Cambridge StructuralDatabase5 (CSD), Shimoni and Glusker had pointed out in 1994that the X−H···F−C (X = C, N, O) interactions are weakcompared to CO···H−X interactions, but their contribution tocrystal packing cannot be ignored.6 Howard et al. in 1996commented on the weak acceptor abilities of the C−F groupbased on the database and computational studies.7 Theyconcluded that the short contacts of the type C−H···X wererare. They also pointed out from theoretical calculations that theC(sp3)−F is a better hydrogen bond acceptor than C(sp2)−F.Furthermore, Dunitz and Taylor, based on their combined CSDand ab initio calculations, concluded that “organic fluorine hardlyever accepts hydrogen bonds”.8 This conclusion was based onthe notion that a covalently bound fluorine has low protonaffinity and is also unable to modify it by intramolecular electrondelocalization and intermolecular “cooperative effects”. Dunitzonce again emphasized9 that organic fluorine is incapable ofproviding stability by dimer formation in his study on fluorinatedand perfluorinated hydrocarbons using PIXEL10 calculations.Thalladi et al., in 1998 for the first time, revealed the importanceof “organic fluorine” in crystal packing, while investigating thestructures of a number of fluorinated liquids using the newlydeveloped technique of in situ crystallization.11 The authorsalso concluded that the C−F group prefers to form C−H···Finteractions rather than C−F···F contacts. This trend was foundto be different for the heavier halogens analogues. In the pastdecade, a number of research groups have been extensivelyinvolved in the experimental and computational structuralstudies on fluorinated organic compounds and have indicatedthat C−H···F interactions may be termed as weak hydrogenbonds and can be used for building a supramolecular architectureinvolving these intermolecular interactions. It has been shown inthe cases of a number of fluorinated tetrahydroisoquinolines thatthe presence of one or two C−F groups in a fairly large molecularframework is capable of generating various supramolecularsynthons through weak C−H···F interactions although therational for those synthons were not achieved.12 The chloro andbromo analogues of these tetrahydroisoquinolines were found topack differently, involving mostly C−O···X (X = Cl and Br) andother weaker interactions.13 Alonso et al. classified C−H···F−Cinteractions as weak hydrogen bonds through their experimentalrotational spectroscopic studies supported by ab initio computa-tional results.14 The importance of fluorine in generating specificsupramolecular assemblies through C−H···F hydrogen bondsand C−F···F and C−F···π interactions in various differentchemicals and biological systems was understood through atutorial review in 2004.15 It was pointed out that the replacementof H by F has a significant influence in the crystal structure andalso on chemical and physical properties of various small organicmolecules. The cooperative nature of C−H···F hydrogen bondswith C−H···N and N−H···F hydrogen bonds has been shown inthe cases of in situ crystallization of 2-fluoroaniline and 4-fluoroaniline.16 It is noteworthy that the crystal structure of 3-fluoroaniline is still not known. D’Oria and Novoa in 2008 haveshown from their CSD analysis and ab initio calculations that thenature of C−H···F interactions involving two neutral fragmentswere different than in the cases where either or both thefragments were charged.17 They also classified these interactionsas hydrogen bonds, except for the cases where both the fragmentscarry charges of the same sign. The systematic structural analyses
of benzonitrile and fluorinated benzonitrile indicated that theweak directional nature of C−H···F hydrogen bonds haveresulted in subtle structural variation, which in turn resultedinto the increase in the melting points of m-fluorobenzonitrile(mp = 12.5 °C) and p-fluorobenzonitrile (mp 38.5 °C) comparedto the melting points of benzonitrile (mp =−13 °C) and o-fluoro-benzonitrile (mp = −13.7 °C).18 The structural analyses offluorinated and multifluorinated derivatives of benzene havefurther emphasized that though the C−H···F−C interactions areweak, they hold similar directional features like well-establishedhydrogen bonds.19 The structural investigations on halogen-substituted benzanilides concluded that the combined effect ofstrong hydrogen bonds, weak intermolecular interactions likeC−H···F hydrogen bonds, and X···X (X=F,Cl, Br, and I) contactshave significant influence in altering the modes of packingdepending on the position (ortho-, meta-, and para-) and nature(F, Cl, Br, and I) of halogen substitutions.20 Further studies onmultihalogenated benzanilides21a and trifluoromethylated benza-nilides21b have emphasized the fact that the presence of one ormore C−F group(s) can alter the packing of molecules containingstrong hydrogen bond donor and acceptor sites (−CONH−group). A recent tutorial review,22a a highlight,22b and aperspective22c have also underlined the significance of “organicfluorine” in the solid state chemistry. A number of different typesof interactions involving the C−F group have been summarized byBerger et al., in their review.The present understanding of the influence of weak
interactions in directing the packing of small organic moleculesin the presence or absence of strong hydrogen bond donors andacceptors is becoming clearer with the results published in thelast couple of years.23 So, now the current focus is to explore howone can utilize these weak interactions involving the C−F groupin crystal engineering and supramolecular chemistry, as theprediction of crystal structure by the application of crystalengineering is still nontrivial. This implies that, still there is a lotmore to explore in the field of weak noncovalent interactions, asthere is no certainty on the robustness and repetitiveness of thesupramolecular synthons generated by very weak hydrogen bonddonors and acceptors in the crystal lattice. In order to achievebetter understanding of the nature and role of the organichalogen (C−X, where X = F, Cl, and Br) group in directingcrystal packing, one needs to carry out different systematicstudies on various systems, in which the molecules are majorlypacked via very weak hydrogen bonds offered by the said C−Xgroup(s) and other weaker interactions and need to analyze thestrength, directionality, and consistency of the synthons offeredby them. Therefore our aim is to study the weak interactionsoffered by C−X (X = F, Cl, and Br) group(s) in order tounderstand the effectiveness of the supramolecular synthonsformed by the weak hydrogen bonds (involving the halogenatom) and their repetitiveness in building the crystal lattice in thesame system but with different substituents. To understand thebehavior of aromatic C−X (where X = F, Cl, and Br) group(s),we have focused on two marginally different molecularframeworks based on N-benzylideneanilines and azobenzenes.We have recently reported the structural investigations on aseries of fluorine substituted N-benzylideneanilines24a andhalogenated azobenzenes24b using single crystal and powderX-ray diffraction supported by ab initio computational methods. Inthe current study, we have extended our earlier results in anotherseries of halogen (F, Cl, and Br) substitutedN-benzylideneanilines(Scheme 1), which provide us the opportunity to study the role ofvery weak hydrogen bonds and other weaker interactions (such as
C−X···X and C−X···π, where X = F, Cl, and Br) offered by variousC−X (X = F, Cl, and Br) groups present at different positions inthe aromatic rings. The first nine compounds belonging to thisseries were reported by us earlier.23a A detailed description of thestructural reports of the similar compounds deposited in theCambridge Structural Database (CSD)25 have also been included inour earlier publication23a and, hence, they are not being discussedfurther. We have earlier observed that the change in the position ofthe fluorine atom resulted in entirely different packing character-istics of the molecules in the cases of fluorine substitutedN-benzylideneanilines. We also pointed out that the C−H···Fhydrogen bonds showed significant directionality (∠C−H···F >160°). In the current manuscript, we aim to present the varioustypes of supramolecular motifs offered by fluorine, chlorine, andbromine in identical chemical environments and wish to determinethe strengths and the directionality of these intermolecular forces inthe crystal lattices.
■ EXPERIMENTAL SECTIONProcedure for the synthesis of all the compounds has been given in theSupporting Information. Scheme 1 describes all the molecules synthesizedand the method of nomenclature used in this manuscript. Out of 36synthesized compounds, 27 compounds were found to be solids at roomtemperature (25 °C), while the remaining nine compounds [compoundnos. (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.
The * indicates the compounds which are found to be liquids at 25 °C.
All the synthesized compounds were characterized by 1H NMR (400MHz, Bruker Biospin Advance-III NMR spectrometer) (Figures S1 ofthe Supporting Information: 1 to 36) and FTIR (Bruker Tensor 72,equipped with diamond cell ATR) (Figure S2 of the SupportingInformation: 1 to 36] spectroscopy. Powder X-ray Diffraction (PXRD)
data were recorded on a Rigaku Ultimia IV diffractometer using parallelbeam geometry with Cu Kα radiation. The observed PXRD patternshave been compared (using WINPLOTR26) with the simulated PXRDpatterns 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 DSCtraces for all the solid compounds are given in Figure S4 of theSupporting Information (1 to 36). The labeling of atoms is shown asthermal ellipsoid plots drawn at 50% probability for the non-H atomsusing Mercury. (Figure S5 of the Supporting Information: 1 to 32).
■ THEORETICAL CALCULATIONS
Due to unavailability of the strong hydrogen bonding sites in ourcurrent system studied, the only interactions that are found to bepresent in the crystal structures are either weak hydrogen bondsor the van der Waals interactions. Out of all these interactionsobserved in the crystal structures we studied, our main interestwas to look for the role played by the C−H···X (X = F, Cl, andBr) 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, havebeen computed using Gaussian 09.28 Gauss View29 has been usedas a graphical interface for Gaussian 09. The coordinates of suchdimers were taken from their respective crystal structures andwere used for the calculation of the stabilization energy providedby them without further optimization. If a dimer formed by twomolecules was found to have more than one type of interaction(say one C−H···X and one C−H···π) then the halogen atom wasexchanged by a H atom (placed at 0.95 Å from the C atom towhich the halogen was bonded) to remove the contribution ofthe stabilization energy contributed by the interaction mediatedby the halogen atom. Then the stabilization energy of the dimerwas recalculated to determine the contribution of the otherinteraction (say C−H···π) in the total stabilization energy andthereafter the contribution from the C−H···X interaction wascalculated by taking the difference of both energies. Allcalculations were performed by using Gaussian09 at the secondorder Møller−Plesset perturbation method (MP2)30 with the6-31+G(*) basis set. The energies obtained for these dimerswere corrected for the basis set superposition error (BSSE) byusing the counterpoise method.31 To study the topologicalproperties 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 energycalculation. From these wave function files, the topology ofelectron density distribution can be analyzed by Bader’s quantumtheory32 of atoms in the molecule. AIM200033 was used tocompute the bond paths and bond critical points between theinteracting atoms. (3, −1) Bond critical points (BCPs) werefound for each C−H···F short contacts encountered in thevarious structures reported here. The topological properties,namely electron density (ρ), and the Laplacian of the electrondensity (∇2ρ) at the (3, −1) BCPs are listed in the Tablescontaining the geometrical parameters of the intermolecularinteractions. The positive sign of the Laplacian at all the BCPsfound between the interacting H and F atoms is an indication ofclosed shell type interaction (like the hydrogen bond).
■ RESULTS AND DISCUSSION
In this mauscript, we are reporting the structures of 32 newcompouds and we intend to present a vivid structural comparisonof the new compounds with those reported earlier.23a For the
Scheme 1
aNote: The compounds containing both Cl and Br have been keptaside from this manuscript.
convenience of readers and for a better understanding, we wouldlike to subdivide all the compounds into various groups such thatthe halogen substitution in one ring is kept constant and the sameis varied in the other ring. In the discussion below, we will use “A”as an abberviation for the phenyl ring originating frombenzaldehyde and “B” for the phenyl ring originating fromaniline. An in depth structural description of all these compoundsalong with their figures can be found in the SupportingInformation. A few representative figures and the Tables forweak interactions have been included in the following segmentfor the purpose of the discussion. Class 1: when F is at the paraposition of the A ring and (1a) the para position of the B ring issubstituted by F, Cl, and Br (1, 43, 25), (1b) the meta position ofthe 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 byF, Cl, and Br (5, 47, 29), and (2c) the ortho position of the B ringis substituted by F, Cl, and Br (6, 48, 30). Class 3: when F is at theortho position of the A ring, (3a) the para position of the B ring issubstituted by F, Cl, and Br (7, 49, 31), (3b) the meta positionof 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 issubstituted by F, Cl, and Br (7, 40, 22). Class 5: when F is at themeta position of the B ring, (5a) the para position of the A ring issubstituted by F, Cl, and Br. (2, 35, 17), (5b) the meta positionof 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 byF, Cl, and Br (6, 39, 21), and (6c) the ortho position of the A ringis substituted by F, Cl, and Br (9, 42, 24).
Structural Comparison of the Compounds Belongingto Classes 1a and 4a. The compound 1, having F at the paraposition of both rings, crystallizes in the centrosymmetric triclinicP1 space group with Z = 2. The packing of molecules of 1 in the crystalstructure elucidates the formation of molecular sheets through theC−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 entirelydifferent supramolecular motifs in the crystal lattice. In 43, typeI C−Cl···Cl−C interactions along with weak C−H···F andC−H···Cl hydrogen bonds have been found to generate ahexameric network as shown in Figure 1b. In the case of 25, weencountered a monoclinic structure with Z′ = 3, and we observedthat the molecules pack majorly by C−H···N hydrogen bondsand 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 and16F2). Both 16F1 and 34 crystallize in the monocliniccentrosymmetric P21/c space group with Z = 4 and areisostructural. By the utilization of C−H···F hydrogen bondsinvolving H12 with F1, zigzag molecular chains were fashioned insuch a way as were found in the case of 1. The replacement of F inthe A ring by Cl and Br has resulted in the interconnection of thepair of antiparallel chains, through the C−H···Cl hydrogen bondsin the case of 34 and by type IC−Br···Br−C interactions in the caseof 16F1 (Table 1 and Figure 1, panels d and e). The homohalogeninteractions found in 16F1 are in contrast to the observation madebyNayak et al.20 in the cases of fluorinated benzenanilides, in whichpreference for type II geometry for homo/hetero halogen shortcontacts involving heavier halogens (Br and Cl) in the solid statehave been revealed. It is interesting to note that the structure of16F2 consists of an entirely different kind of molecular network viathe C−H···F hydrogen bond involving the imine proton and theC−H···Br hydrogen bond (Figure 1f), thereby crystallizing inthe orthorhombic Pna21 space group with Z = 8 and Z′ = 2. All thecompounds described above displayed several different weakC−H···π interactions aswell (Table S1of the Supporting Information).
Table 1. Details of Intermolecular Interactions, Computed Stabiliztion Energies, and Topological Parameters of Compounds 1,43, 25, 34, 16F2, and 16F1
Various molecular networks formed by these C−H···π interactionshave been described in the Figure S1 (panels a−h) of theSupporting Information.The stabilization energies calculated by using Gaussian 09 for
the molecular dimers formed by weak C−H···F hydrogen bonds
were found to be between 1.0 and 2.5 kcal/mol in the cases ofcompounds 1, 43, 34, 16F1, and 16F2, while for C−H···Nhydrogen bonds, it lies in the range of 4−5 kcal/mol. The AIMcalculations indicated the existence of BCPs in all the cases ofC−H···F hydrogen bonds and C−X1···X2 interactions with very
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 asymmetricunit 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···Clhydrogen bonds in 34, (e) zigzag chains formation through weak C−H···F hydrogen bonds, which further interact by type I C−Br···Br interaction in16F1, and (f) molecular network, which is found to form by weak C−H···F and C−H···Br hydrogen bonds in 16F2.
low values of electron densities (ρ) and Laplacians (∇2ρ). Thesevalues are in agreement with the values reported from experimentalcharge density analysis for weak C−H···O hydrogen bonds andweak interactions, as reported by Munshi and Guru Row earlier.34
In this particular set of compounds, it has been found that thereplacement of F in the A ring by the heavier halogens havecompletely altered the crystal packing, while the same kind ofreplacement in the B ring has kept some features of thedifluorinated compound (i.e., formation of molecular chainsinvolving H12 with F1) unaffected, as described above.Structural Comparison of the Compounds Belonging
to Classes 1b and 5a. Compound 2 crystallizes in themonoclinic centrosymmetric P21/c space group. C−H···Fhydrogen bonds are involved in forming head-to-head and tail-to-tail dimers across the inversion centers, thereby generatingmolecular layers (Table 2, and Figure 2a). These layers arefurther interacted with the neighboring layers by weak C−H···Fhydrogen 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 compoundsbelonging to the subclasses 1b and 5a crystallize in P21/c spacegroup with Z′ = 1. Futher, the compounds 44 and 26 of class 1bare isostructural, but with different packing features incomparison to 2. In the cases of the structures of 44 and 26,the molecular chain formation occurs through a weak C−H···Fhydrogen bond and these chains are further interconnected throughtype II C−F···X (X = Cl or Br) (in 44 and 26, respectively) heterohalogen interactions thus giving rise to a sheetlike structure in the acplane (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 packingcharacteristics with compound 2. In the crystal packing of both35 and 17, molecules related by center of inversion are formingdimers involving H9 and H1 with F1 (Table 2 and Figure 2,panels d and e). The fluorine atoms involved in these dimers havebeen found to have bifurcated C−H···F hydrogen bonds. Thesedimers 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 respectivelattices (Table S2 and Figure S2, panels a−c, of the SupportingInformation), while the weak C−H···π interactions have beenreplaced by weak C−H···X (X = Cl or Br) hydrogen bonds in thecases of 35 and 17 (Table 2 and Figure 2, panels d and e).
The stabilization energies of the dimers (IEG09) formed byC−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 energiesof 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 themolecules participating in the dimer formation. The stabilizationenergies of the dimers (IEG09) formed by the C−H···F hydrogenbonds in the cases of 35 and 17 are about−3.5 kcal/mol, which ismuch more than those observed earlier as four C−H···Fhydrogen bonds have been found to involve between the twointeracting 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 lowvalues of electron densities (ρ) and Laplacians (∇2ρ) as seenearlier, indicating the weak closed shell nature of theseinteractions. In the case of structures belonging to the group1b, it has been found that the replacement of F in the A ring bythe heavier halogens have inroduced different packing features bythe introduction of interhalogen contacts (Figure 2, panels a, b,and c), while the same kind of replacement in the B ring hasgenerated different packing characteristics by the introduction ofweak C−H···X (X = Cl or Br) hydrogen bonds (Figure 2, panelsa, d, and e). It is also noteworthy that change in the crystalpacking as well as in the interaction energies involving C−H···Fhydrogen bonds have not been seen just by the interchange of Clwith Br or vice versa (Table 2 and Figure 2, panel b, vs panels cand d vs panel e).
Structural Comparison of the Compounds Belongingto Classes 1c and 6a. Compound 3 crystallizes in themonoclinic noncentrosymmetric P21 space group with Z′ = 2,and the molecules within the asymmetric unit are interconnectedvia weak C−H···π interactions (Table S3 of the SupportingInformation). Both the molecules present in the asymmetric unitform molecular chains through short, highly directional, andsignificantly stabilizing C−H···F hydrogen bonds involving theimine hydrogen H1 with F1 and H14 with F4, respectively(Table 3 and Figure 3, panels a and b). In one of the molecules ofthe asymmetric unit, these chains are further connected byanother 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 dataon 45 and 27 did not indicate any sharp solidification ormelting features. Several trials of crystal growth using in situcrystallization technique had failed to grow single crystals
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)
suitable for the structural analysis of these compounds. In thecases of 45 and 27, the replacement of F at the ortho position of
the B ring by Cl and Br, respectively, removed the possibilty ofweak C−H···F hydrogen bonds involving the imine hydrogen,
Figure 2. (a) Propagating dimers in 2, which are further interconnected through C−H···F hydrogen bonds, (b) formation of molecular sheets by thecombination 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 hydrogenbond 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 ofdimers 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 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)
3 C1−H1···F2 2.32 162 x + 1, y, z −4.76 0.068 1.110C14−H14···F4 2.30 161 x − 1, y, z −4.75 0.068 1.135C10−H10···F1 2.66 131 x, y, z + 1 −0.68 0.034 0.603
36F1 C1−H1···F1 2.40 160 1 − x, −1/2 + y, 1/2 − z −4.84 0.056 0.98718F1 C1−H1···F1 2.44 156 x + 1, y, z −4.97 0.054 0.95818F2 C1−H1···F1 2.35 168 x, y − 1, z −5.13 0.060 1.045
C14−H14···F2 2.41 159 x, y + 1, z −5.14 0.054 0.958C23−H23···F1 2.43 142 x, y − 1, z −1.27 0.049 0.927
36F2 C1−H1···F1 2.37 173 x, y − 1, z −4.98 0.054 0.990C14−H14···F2 2.38 168 x, y + 1, z −5.14 0.054 0.990
which was present in the case of 3, thereby lowering the meltingpoint of 45 and 27. A similar trend was earlier observed byVasylyeva 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 crystallizein the orthorhombic noncentrosymmetric P212121 space groupwith Z = 4 and are isostructural. In the structures, 36F1 and 18F1
chains have been found to form through C−H···F hydrogenbonds (involving H1 with F1) along the b axis, and C−H···πinteractions 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 structure36F2 was solved in the orthorhombic Pna21 space group. Allthese three structures (3, 36F2, and 18F2) have twomolecules in
Figure 3. (a) Formation of sheets in one of themolecule of the asymmetric unit of 3, (b) chain formation in secondmolecule 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) ribbonformation through C−H···F hydrogen bond and their interlinkage via C−H···π interactions in 18F1, (e) chain formation through C−H···F hydrogenbond 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.
the asymmetric unit. The common trend that is found in all thestructures (3, 36F1, 36F2, 18F1, and 18F2), even with both themolecules of the asymmetric unit (3, 36F2, and 18F2), is that theF atom present in the ortho position of the B ring has been foundto be involved in the formation of weak C−H···F hydrogenbonds involving the acidic imine hydrogen H1 (Table 3 andFigure 3, panels a, b, c, d, e, and f). The chains formed throughthis interaction interact with other chains, either formed by theset of same molecules (36F1, 18F1, and 18F2) or by the set ofother molecule of the asymmetric unit (3 and 36F2) throughC−H···π interactions. In the case of the structure 18F2, themolecules constituting the asymmetric unit are interactingthrough 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 highervalues of electron density at their BCPs (0.054−0.068 e Å−3).Also, the values of the stabilization energies of the dimersinteracting through this C−H···F hydrogen bond have beenfound to be much more (∼ 2 kcal/mol) than those observed inthe earlier cases involving aromatic protons (Table 3).Structural Comparison of the Compounds Belonging
to Classes 2a and 4b. Compound 4 crystallizes in the spacegroup P1 with Z = 4 and Z′ = 2. This compound involves theformation of layer motifs through dimeric C−H···F hydrogenbonds, which further interlink with other layers by weak C−H···Fhydrogen bonds (Table 4 and Figure 4a) and C−H···πinteractions (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 thesubclass 2a. While, 46 exists in only one form, two differentpolymorphs are found for the compound 28, namely 28F1 and28F2. The structures 46 and 28F1 were solved in the monoclinicnoncentrosymmetric P21 space group withZ = 2 with similar unitcell dimensions and packing features in their crystal structures.Weak C−H···F hydrogen bonds (involving H5 with F1) lead tothe formation of zigzag chains in the crystal structures of 46 and28F1 (Table 4 and Figure 4, panels b and c). A chain of heterodimers 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 SupportingInformation and Figure 4, panels d and e) has also been
observed in the crystal structures of both 46 and 28F1.Therefore, we consider these to be isostructural. The structure28F2 was solved in the orthorhombic noncentrosymmetricP212121 space group and displays a completely different crystalpacking involving the C−H···N hydrogen bond and weak type IIC−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 thesubclass 4b crystallize in the monoclinic centrosymmetric P21/cspace group with Z = 4. In the ab plane, molecular ribbonlikeformation involving C−H···F hydrogen bonds has been seen(Table 4 and Figure 4, panels g and h) in the similar fashion aswas observed in the cases of structures 34 and 16F1 (Table 1 andFigure 1, panels d and e). Then these molecular ribbons areinterconnected through type I C−X···X (X = Cl or Br)interactions (Table 4 and Figure 4, panels g and h). Very weakC−H···π interactions in the ac plane have also been identified inbetween the sheets formed by C−H···F hydrogen bonds andC−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 andLaplacian (∇2ρ) at the BCP have been found to be similar to thevalues observed in the cases of weak interactions observed andare reported in the Table 4. In this case also, the structuralfeatures observed in the case of 4, has not been carried by thecompounds belonging to its group members, in which one of thefluorine was replaced by Cl or Br.
Structural Comparison of the Compounds Belongingto Classes 2b and 5b. All the compounds belonging to thesubclasses 2b (5, 47, 29) and 5b (5, 38, 20) exist as liquids at25 °C. Among these, the crystal structure of 5 could be determinedusing the in situ crystallization technique, while crystals of theothers could not be grown in the same way. The DSC data of thecompounds 20 and 47 have not shown any indication ofsolidification in the cooling and heating cycles (25 °C to−100 °Cand heated back to 25 °C) [Table S1 and Figure S4 (5 and 32) ofthe Supporting Information]. For the compounds 29 and 38,though some features were seen in their DSC traces [Table S1 and
Table 4. Details of Intermolecular Interactions, Computed Stabilization Energies, and Topological Parameters of Compounds 4,46, 28, 37, and 19
Figure 4. (a) Formation of dimers and their interconnection throughC−H···F hydrogen bonds in 4, (b) zigzag chains formation by C−H···F hydrogen bonds in46, (c) formationof a similar kindof chains byC−H···Fhydrogen bonds in28 aswas seen in46, (d) propagating dimers in46 formed via combinationofC−H···Fhydrogenbonds andC−H···π interactions, (e)C−H···Fhydrogen bond andC−H···π interactions, whichwere foundbetween the chains of heterodimers in28F1,(f) formation of molecular chains through weak C−H···N hydrogen bonds and C−F···Br interactions in 28F1, (g) molecular sheet formation through weakC−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.
Figure S4 (14 and 23) of the Supporting Information], yet thecompounds could not be crystallized in situ.Structural Comparison of the Compounds Belonging
to Classes 2c and 6b. Among the compounds belonging to thesubclass 2c (6, 30, 48), only 6 exists in the solid state at 25 °C,while others are liquids at the same temperature. Compound 6packs in the lattice by utilizing C−H···F hydrogen bondsinvolving imine hydrogen (H1) and C−H···π interactions. Whenthe F atom on the B ring (which is involved in the formation ofC−H···F hydrogen bonds in 6) was replaced by Cl or Br,probably due to the absence of that particular C−H···F hydrogenbond, the compounds 30 and 48 exist as liquids as has been seenin the case of 3. Crystal structures of 48 and 30 could not be
determined as none could be crystallized when cooled fromroom temperature to −170 °C in a quartz capillary on thediffractometer 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 celldimensions and having almost similar packing features.Molecular chains are formed through C−H···F hydrogenbonds involving imine hydrogen (i.e., H1) in compound 6(Table 5, Figure 5a), while in the compounds 39 and 21, the Fatom has been found to be bifurcated and form hydrogen bondsby involving both imine and aromatic hydrogen (H1 and H3,respectively). Futher, these chains are interlinked through quasitype I/type II interhalogen C−F···X (X =Cl or Br) interactions35
Table 5. Details of Intermolecular Interactions, Computed Stabiliztion Energies, And Topological Parameters of Compounds 6,39, and 21
6 C1−H1···F1 2.47 163 x − 1, y, z −4.09 0.041 0.76839 C1−H1···F1 2.46 153 x + 1, y, z −4.92 0.048 0.864
C3−H3···F1 2.66 149 x + 1, y, z 0.027 0.558C6−Cl1···F1 3.02 133, 161 1 − x, 1/2 + y, 1/2 − z −0.10 0.054 0.966
21 C1−H1···F1 2.49 152 x − 1, y, z −5.30 0.045 0.823C3−H3···F1 2.64 150 x − 1, y, z 0.029 0.594C6−Br1···F1 3.05 135, 161 −x, −1/2 + y, 1/2 − z −0.43 0.054 0.966
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 throughC−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···Brinteractions.
along the b axis (Table 5 and Figure 5, panels c and d) and viaweak C−H···π interactions along the c axis in the compounds 39and 21 (Table S5 of the Supporting Information and Figure 5a).But in the case of 6, the molecular chains formed are furtherpropagating 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 canbe concluded that 39 and 21 are isostructural but differentfrom 6.The C−H···F hydrogen bonds involving H1 have higher
electron densities at their BCPs (∼0.048 e Å−3) as was also seenin the cases of compound 3, 36F1, 36F2, 18F1, and 18F2. Also,
Table 6. Details of Intermolecular Interactions, Computed Stabiliztion Energies, and Topological Parameters of Compounds 7,49, 31, 40, and 22
49 C6−H6···Cl1 2.99 130 x + 1, −y + 3/2, z + 1/2 −0.71 0.034 0.50731 C6−H6···Br1 3.07 134 x − 1, −y + 1/2, z − 1/2 −0.88 0.041 0.48340 C12−H12···Cl1 2.99 136 x, −y + 1/2, z + 1/2 −0.68 0.034 0.48322 C12−H12···Br1 3.08 133 x, −y + 1/2, z + 1/2 −0.37 0.034 0.435
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 furtherinterconnect through weak C−H···π interactions in 49, (c) chains formation and their interconnection via weak C−H···Br hydrogen bonds and weakC−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) molecularchain formation through C−H···Br hydrogen bonds in 22.
the values of the stabilization energies of the dimers formed bythis C−H···F hydrogen bond lie in the range between −4.09 and−5.30 kcal/mol. The C−H···F hydrogen bonds formed involvingH3 in the case of the compounds 39 and 21 have lower values ofelectron densities at their BCPs (0.027 and 0.029 e Å−3), thustheir contribution toward the sabilization energy of the dimersfomed byH1 andH3 with F1must be lesser in comparison to thestabilization energy provided by the C−H···F hydrogen bondinvolving H1 with F1.Structural Comparison of the Compounds Belonging
to Classes 3a and 4c. Compound 7 crystallizes in themonoclinic space group P21/c with Z = 2 (Z′ = 0.5). Themolecule exhibits positional disorder around the CN bondwith a 0.5 occupancy, whichmakes themolecule symmetrical andthus only half of the molecule is present in the asymmetric unit.The molecules of compound 7 pack in the crystal lattice by theutilization of dimeric C−H···F hydrogen bonds to formmolecular sheets (Table 6 and Figure 6a), which further getinterlocked through both C−H···F hydrogen bonds andC−H···π interactions (Table S6 and Figure S6a of the
Supporting Information), thereby generating different kinds ofsupramolecular 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 and4c was disordered. Chains along the a axis are formed by weakC−H···Cl and C−H···Br hydrogen bonds, respectively, involvingthe same H atom (H6) (Table 6 and Figure 6, panels b and c) in49 and 31, respectively. The chains thus formed are then held byweak C−H···π interactions in the crystal lattice in both thecompounds (Table S6 and Figure S6, panels a and b, of theSupporting 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 andFigure 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 inthe packing of molecules in the crystal lattice. Also, no
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)
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 ofheterodimers in 50, (c) formation of heterodimers in 32 via weak C−H···F hydrogen bonds, (d) network formation through C−H···F hydrogen bondsin 41, and (e) C−H···F hydrogen bonds in 23, which form a similar kind of network as was found in 41.
interhalogen interactions have been observed in the structures ofthe 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 muchmore than the stabilization provided by weak C−H···X (X = Clor Br) hydrogen bonds in the compounds 49, 31, 40, and 22. Thevalues of the electron density and Laplacian found at the BCPs ofC−H···X (X = F, Cl, or Br) hydrogen bonds have almost similarvalues except for the C−H···F hydrogen bond involving H1 withF1, 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 monocliniccentrosymmetric P21/c space group with Z = 4. Thesecompounds display similar structural features. In compound 8,the F atom on the para position of the B ring does not participatein any kind of interaction. Therefore, the replacement of thatparticular F by Cl or Br, has not brought any alteration in thecrystal packing. All the compounds belonging to this group areinvolved in the formation of heterodimers by the use of weakC−H···F hydrogen bonds, involving H9 and H1 with F1 (Table 7a,Figure 7, panels a, b, and c). The molecular dimers thus formed arethen interconnected again through C−H···F hydrogen bonds(involving F1, which is bifurcated in the crystal lattice) and thuspropagating along the crystallographic b axis.However, the replacement of the F present at the ortho-
position of the A ring by Cl or Br (41 and 23) has resulted intocompletely different crystal packing. All these three compoundsexist as liquids at 30 °C. Compound 8 was crystallized by in situcrystallization technique, while the crystals of the compounds 23and 41 were grown in a refrigerator maintained at −20 °C andthose were mounted quickly in a cold room at about 20 °C andwere transferred to the diffractometer with the Oxfordcryosystem maintained at 0 °C. Structures 41 and 23 are solvedin the orthorhombic noncentrosymmetric P212121 space groupwith Z = 4 and are isostructural. Both the structures 41 and 23,are disordered due to the rotation of the aryl ring around theN−C(Ar) bond. Therefore, the fluorine atom on the B ring hasbeen 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. Boththe compounds involve the formation of linear chains throughthe C−H···F hydrogen bond (involving H5 with F1A) (Table 7and Figure 7, panels d and e) in their crystal lattices. The atomF1B is trifurcated and forms hydrogen bonds with H1 and H9B
and is also involved in the type I interhalogenC−F···X (X=Cl or Br)interactions in 41 and 23, respectively (Table 7 and Figure 7, panelsd 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 dimersformed in the cases of 41 and 23 are much less than thosefound for 8, 50, and 32. The values of the electron densitiesand Laplacians found at the BCPs, which exist betweenC−H···F hydrogen bonds, belonging to these groups arenearly similar.
Structural Comparison of the Compounds Belongingto Classes 3c and 6c. Among the compounds belonging to thegroup 3c (9, 51, 33), compound 9 exists as two polymorphs (9F1and 9F2). The structures 9F1 and 51 were solved in the P21/cspace group, while the structures 9F2 and 33 were solved inP212121 and Pbcn space groups, respectively. All the compoundsof this group have positional disorder around the CN bond.Structures 9F1 and 9F2 were refined with 0.5 occupancy of boththe parts, while in structures 33 and 51, the occupancy ratio ofthe two parts were found to be 0.91:0.09 and 0.55:0.45,respectively. Compound 9F2 pack through bifurcated C−H···Fhydrogen bonds in the lattice (Table 8 and Figure 8b), while therest of the compounds belonging to the group 3c form dimers intheir respective crystal structure through C6−H6···X (X = F1 orCl1 or Br1) hydrogen bonds (Table 8 and Figure 8, panels a, c,and d). Then, these dimers propagate in the lattice throughC−H···Cl hydrogen bonds in the case of compound 51 (Table 8and Figure 8c) and through C−H···π interactions in the case of33 (Table S8 of the Supporting Information and Figure 8d),while in 9F1, no other interaction between the molecular dimerhas 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 centrosymmetricPbca space group with Z = 8. The molecules of 42 have beenfound to interact through the formation of two types of heterodimers using weak C−H···F and C−H···N hydrogen bondsparallel to the b axis (Table 8 and Figure 8e) and by involvingC−H···F and C−H···Cl hydrogen bonds parallel to the a axis(Table 8 and Figure 8f). Compound 24 crystallizes in themonoclinic centrosymmetric P21/c space group with Z = 4. Themolecules related by the center of inversion interact throughdimeric C−H···F hydrogen bonds. The dimers thus formed are
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)
further interlinked among themselves by another C−H···Fhydrogen bond (Table 8 and Figure 8g). In this case, the F atomhas been found to be trifurcated and the Br atom in the A ringdoes not involve in any kind of intermolecular interaction. Noneof these compounds have displayed any C−H···π interaction.
Thus, in these set of compounds, much similarity in theircrystal structures has not been observed. It has been foundthrough Gaussian09 calculations that the stabilization energiesprovided by C6−H6···X (X = Cl1 or Br1) hydrogen bonds arenearly the same in the compounds 51 and 33, but lesser than that
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 viabifurcated C−H···F hydrogen bonds, (c) formation of dimers and their propagation through weak C−H···Cl hydrogen bonds in 51, (d) moleculardimer 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 extensionin 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···Fhydrogen bonds, which interconnect the molecules in the crystal structure of 24.
provided by the C6−H6···F1 hydrogen bond in the case of 9F1.The values of the electron density and the Laplacian at the BCPsfound between C−H···X (X = F, Cl, or Br) hydrogen bonds liein the range of 0.026−0.037 eÅ−3, while values for the same involvingthe imine proton in C−H···N hydrogen bond is 0.054 e Å−3.It is evident from the above structural discussion that these
molecules mainly pack involving C−H···F hydrogen bonds withthe cooperative effects of other weaker interactions such asC−X···X and C−H···π. We have plotted the electron densities(ρ, e Å−3) and the Laplacians (∇2ρ, e Å−5) at the BCPs of all theC−H···F hydrogen bonds against the Rij (length of the bond pathas found using AIM2000) using SigmaPlot36 and the plottedpoints are fitted with a suitable exponential function. These plotswith the equations and the corresponding values of R2 arereported in the following figures (Table S8 of the SupportingInformation), (Figure 9, panels a and b). These plots show
similar trends as were observed byMunshi andGuru Row in theiranalysis of C−H···O hydrogen bonds using both experimentaland theoretical charge density analysis.34 Therefore, it may beconcluded that C−H···F interactions can also be classified asweak hydrogen bonds similar to C−H···O hydrogen bonds.In the following paragraphs, we would like to focus on the
various features and trends that we have found in the structuresreported herein. (1) The above structural description clearlyindicates that the chloro- and bromo- analogues display similarpacking features and in many cases they are found to be
isostructural in general, while the corresponding fluorinatedderivatives have displayed different types of packing character-istics, thereby yielding different crystal structures altogether.Only a few chloro- and bromo- analogues (43 and 25 and 42 and24) did not show similarity in their interactions and the cystalpacking as was observed in all the other cases. (2) We observedthat some of the packing features of the difluoro- compounds(1−9) have been carried forward in the crystal packing of theircorresponding chloro- and bromo- analogues in the eightcompounds studied here. The first example of this feature hasbeen observed in the cases where the fluorine atom is present atthe para- position on the B ring, and either Cl or Br is present atthe para- or meta- position on the A ring (classes 4a and 4b). Inthese cases, the formation of the same type of zigzag chainsthrough C−H···F hydrogen bonds involving the para-F on the Bring (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 ortho- position onthe B ring and F/Cl/Br is present at the para- or meta- positionson the A ring, the structures of those compounds have beenmajorly influenced by the intermolecular C−H···F hydrogen bond(with stabilization energy in the range of 4−5 kcal/mol), involvingthe imine hydrogen and the o-F of the B ring. It is noteworthy thatthe halogen atom present on the A ring generally did not participatein 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 thesynthons found in 3, 6, and 8 was experienced when thenoninteracting fluorine was replaced by Cl or Br in the cases ofcompounds 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 isreplaced byCl or Br, the possibility of the robust synthon found in 3and 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···Fhydrogen bonds involving the imine H have higher stabilizationenergies (4−5 kcal/mol) than those involving aromatic protons (<4kcal/mol). This feature is further supported by the higher values ofρ (0.041−0.068 e Å−3) and ∇2ρ (0.77−1.14 eÅ−5) at the BCPsfound for the concerned C−H···F hydrogen bonds in the dimersinvolving imine H compared to those involving aromatic protons [ρ(0.023−0.043 e Å−3) and ∇2ρ (0.47−0.80 eÅ−5)].
■ CONCLUSIONSThis study reveals that the “organic fluorine”, present in a seriesof isomeric N-benzylideneanilines, as a substituent displaysdistinctive features in the crystal packing of the fluorinatedmolecules in comparison to its heavier halogen analogues. Thissystematic analysis not only reinforces the uniqueness of “organicfluorine” among the halogens but also emphasizes the robustnessof the supramolecular synthons involving C−H···F hydrogenbonds in the absence of −COOH, −OH, −NH−, −NH2, etc.groups. The stabilization energies supported by the topologicalproperties highlight the strength and directional nature ofC−H···F hydrogen bonds. The dimers formed by the C−H···Fhydrogen bonds involving the imine hydrogen have been foundto provide similar stabilization as compared to other weakhydrogen bonds such as C−H···N and C−H···O. The heavierhalogens have been found to prefer halogen···halogen inter-actions over C−H···X (X =Cl or Br) hydrogen bonds, which is inaccordance with earlier observations by other research groups.The AIM analyses on the dimers formed by C−H···F have shown
Figure 9. (a) Plot of electron density at BCP vs Rij and 9(b) plot ofLaplacian at BCP vs Rij.
the presence of BCPs between the interacting atoms with thepositive value of Laplacian, indicating the closed shell type ofinteraction between the atoms involved, irrespective of thestabilization energies and the nature of concerned hydrogeninvolved. Therefore, the C−H···F interactions observed in thesecompounds should be considered as weak hydrogen bonds. Inthe current manuscript, efforts have been made to gain a betterunderstanding of the fluorine mediated intermolecular inter-actions in the absence of strong hydrogen bonds.
■ ASSOCIATED CONTENT*S Supporting InformationThis material is available free of charge via the Internet athttp://pubs.acs.org.
■ ACKNOWLEDGMENTSThe authors thank IISER Mohali for research funding, X-ray,NMR, computer, library, and all other instrumental andinfrastructural facilities. G.K. thanks CSIR for a researchfellowship. We thank Dr. Parthapratim Munshi and Dr. SagarikaDev for useful discussions.
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■ NOTE ADDED AFTER ASAP PUBLICATIONThis paper was published ASAP on February 27, 2014, withpanels g and h missing in Figure 4. The corrected version wasreposted on March 4, 2014.
