Crystal-to-Crystal Thermal Phase Transformation of Polymorphs of

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Crystal-to-Crystal Thermal Phase Transformation of Polymorphs of Isomeric 2,3-Naphthalene Diol Ditoluates: Mechanism and Implications for Molecular Crystal Formation and Melting Published as part of the Crystal Growth & Design virtual special issue IYCr 2014 - Celebrating the International Year of Crystallography Majid I. Tamboli,† Shobhana Krishnaswamy,‡,§ Rajesh G. Gonnade,*,‡ and Mysore S. Shashidhar*,† †

Division of Organic Chemistry, and ‡Center for Materials Characterization, CSIR-National Chemical Laboratory, Pune 411 008, India § Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India S Supporting Information *

ABSTRACT: Isomeric para- (1) and meta- (2) ditoluate derivatives of naphthalene 2,3-diol exhibited polymorphism producing three (Forms 1I, 1II, 1III) and two (Forms 2I, 2II) polymorphs each, respectively, depending on the solvent and conditions of crystallization. Crystal forms 1I, 1II, and 2I could be obtained repeatedly, whereas crystal forms 1III and 2II were obtained (separately) in one of the crystallization experiments, each. All the crystal forms were stable at ambient conditions, except for Form 2II, which disintegrated to a powder over 4−5 days. In contrast, the ortho-ditoluate (3) of naphthalene 2,3-diol did not exhibit polymorphism; it yielded fibrous chiral crystals from different solvents/conditions. Crystal structure analysis of all these polymorphs revealed dominance of energetically similar weak intermolecular interactions such as C−H···O, C−H···π, π···π, and their interplay in molecular aggregation resulting in polymorphic modifications. Differential scanning calorimetry (DSC), hot stage microscopy, single crystal and powder X-ray diffraction measurements revealed crystal-to-crystal thermal transformation of Forms 1I and 1II crystals to Form 1III crystals and Form 2II crystals to Form 2I crystals. The transformation of Form 1I and Form 1II crystals to Form 1III crystals can be viewed as progressive destabilization of the crystal lattice during heating and converting to metastable phase, whereas the conversion of Form 2II to Form 2I crystals can be considered as reorganization of an unstable crystalline phase to a stable crystalline phase. Hence comparative studies of the structure of stable, metastable, or transient crystals and crystal-to-crystal transformations involving these forms could aid in unraveling the process of crystallization.

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INTRODUCTION The phenomenon of polymorphism1 is one of the most intensely investigated areas of contemporary research due to its increasing relevance in pharmaceutical drugs,2 high energy materials,3 agricultural products,4 and industrially important chemicals.5 Polymorphism in molecular crystals is one of the manifestations of noncovalent intermolecular interactions which play a vital role in the assembly of molecules in a crystal.6 These interactions are generally categorized as strong, weak, and weakest depending on the relative geometries of interacting atoms and energies.7 Among the strong interactions, the O−H···O, N−H···O, N−H···N (hydrogen bonds) have well-defined motifs and often direct the molecular assembly in the crystalline state.8 However, molecules incapable of forming these strong interactions are organized in the crystal lattice via energetically weaker interactions or van der Waals’ forces, and these solids often exhibit polymorphic behavior.6 The relative stability of polymorphs varies, and hence they often exhibit structural phase transitions.9 This is an important aspect of © XXXX American Chemical Society

research relevant to crystal engineering, crystal structure prediction, and structure and property correlation in functional solids. When these transitions are between two or more crystalline phases, analysis of intermolecular interactions can provide clues about the possible molecular movements during phase transformation. Furthermore, if crystal forms relatively unstable under crystallization conditions are encountered, analysis of their structure could aid in understanding the (enigmatic) process of crystallization. Hence although irreproducible crystal forms have less application potential, they could give insight into the mechanism of crystal formation. Our investigations into the crystallization behavior of para-, meta-, and ortho-ditoluates 1−3 (Figure 1) of naphthalene 2,3diol (4) resulted in the formation of polymorphs, some of which were unstable and underwent crystal-to-crystal thermal Received: April 15, 2014 Revised: July 30, 2014

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dx.doi.org/10.1021/cg5005227 | Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

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2−3 days (Figure 2E) and completely disintegrated into a powder in 4−5 days. Crystallization of the o-toluate 3 from all the solvents mentioned above produced fibrous crystals (Figure 2F). Details of X-ray diffraction data collection, structure solution and refinement, differential scanning calorimetry (DSC) analysis, hot stage microscopy (HSM), and powder X-ray diffraction (PXRD) studies are given in the SI.

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RESULTS AND DISCUSSION Polymorphs of the para-Ditoluate 1. Crystallization of the p-ditoluate 1 from diethyl ether yielded two differently shaped crystals: needles and plates, concomitantly. Careful observation of the crystallization process revealed formation of needles (Form 1I) within 10−12 h, whereas the plates (Form 1II) were obtained after 1−2 days in the same flask. This suggested that the needles were formed faster, and the plates were perhaps formed under thermodynamic conditions.6b,12 The fact that the formation of Form 1I or Form 1II crystals could be prevented by varying the solvent of crystallization (see Experimental Section) suggests that the nucleation and crystallization of these polymorphs could be solvent mediated.13 Rapid appearance of Form 1III crystals (blocks) from hot methanol suggests its metastable nature, and its irreproducibility suggests the possibility of a disappearing polymorph.14 DSC analysis (SI, Figure S7) of Form 1I and Form 1II crystals revealed two endotherms; the first endotherm in both the forms indicates structural phase transition [117 °C (Form 1I) and 131 °C (Form 1II)], and the second endotherm was attributed to their melting (145−147 °C). A repeat of the DSC experiment on these crystal forms, cooled after heating beyond the transition temperature, contained only the melting endotherm revealing irreversible phase transition. The DSC profile of Form 1III crystals showed only the melting endotherm. The PXRD pattern (SI, Figure S8) of cooled samples of Form 1I and Form 1II crystals after heating beyond the transition temperature is comparable with the PXRD profile of Form 1III crystals, indicating the conversion of Form 1I and Form 1II crystals to Form 1III crystals. This crystal-to-crystal transformation was also confirmed by HSM (SI, Figure S9) and single crystal XRD studies. Single crystal X-ray analysis revealed that all the three polymorphs of 1 crystallized in the triclinic space group P1̅ having one, two, and four molecules in the asymmetric unit, respectively. The single crystal X-ray diffraction data revealed resemblance between the unit cell parameters of all the three polymorphs (Table 1). Initially, it appeared that unit cells could be transformed into each other, but crystal structures revealed significant conformational differences in the orientation of the toluoyl moieties in all the forms due to free rotation along C− O, O−C, and C−C single bonds (Figure 1). The similarity in

Figure 1. Structures of ditoluates of naphthalene-2,3-diol (4).

phase transitions. Analysis of these crystal structures helped us to arrive at possible mechanisms for their formation. This work is a part of our ongoing study on solid state acyl transfer reactions in crystals.10

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EXPERIMENTAL SECTION

Preparation of Naphathalene-2,3-diolditoluates 1−3. The pditoluate 1 was prepared as reported earlier.11 The ditoluates 2 and 3 were synthesized by the acylation of naphthalene-2,3-diol (4) with mtoluoyl chloride (for 2) and o-toluoyl chloride (for 3) at 115−120 °C. See electronic Supporting Information (SI) for details and compound characterization data. Crystallization. Solubility of the ditoluates 1, 2, and 3 was similar in common organic solvents. A clear solution was obtained by vigorous shaking and/or warming of the ditoluate in the desired solvent, and the solution was allowed to evaporate at room temperature over 2−3 days. Crystallization of 1 from diethyl ether produced needle-shaped crystals in 10−12 h (Form 1I, Figure 2A), whereas thick plates (Form 1II, Figure 2A) appeared after 1−2 days in the same crystallization flask; the quantity of the needles obtained was always more than the plates, consistently. Crystallization of 1 from ethyl acetate, acetone, toluene, nitromethane, dichloromethane, chloroform, carbon tetrachloride (CCl4), and tetrahydrofuran (THF) yielded Form 1I crystals exclusively, whereas Form 1II crystals were obtained from acetonitrile, 2-propanol, methanol, and benzene. In one of the experiments, Form 1III crystals (blocks, Figure 2B) were obtained from a hot solution of methanol, but several attempts to obtain these crystals again yielded only Form 1II crystals. Crystallization of 2 from ethyl acetate, acetone, toluene, nitromethane, dichloromethane, chloroform, acetonitrile, 2-propanol, methanol, benzene, CCl4, and THF yielded thick plates (Form 2I, Figure 2C) exclusively. Crystallization of 2 from ethanol once produced only needle type crystals (Form 2II, Figure 2D). However, further attempts to obtain Form 2II crystals yielded only Form 2I crystals. Form 2II crystals turned opaque at ambient conditions within

Figure 2. Photomicrographs of crystals of ditoluates 1, 2, and 3. (A) Form 1I (needles) and Form 1II (plates) crystals; (B) From 1III crystals; (C) Form 2I crystals; (D) Form 2II crystals; (E) opaque crystals obtained from Form 2II crystals; (F) fibrous crystals of 3. B



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Table 1. Crystallographic Information for Crystals of 1, 2, and 3 crystal data formula Mr crystal size, mm temp (K) crystal system space group a [Å] b [Å] c [Å] α [°] β [°] γ [°] V [Å3] Z F(000) Dcalc [g cm−3] μ [mm−1] Ab. correction Tmin Tmax 2θmax total reflns unique reflns obs reflns h, k, l (min, max) Rint no. of para R1 [I > 2σ(I)] wR2 [I > 2σ(I)] R1 (all data) wR2 (all data) goodness-of-fit Δρmax, Δρmin (e·Å−3) CCDC no.

Form1I C26H20O4 396.42 0.61 × 0.31 × 0.07 90(2) triclinic P1̅ 7.4604(8) 9.9210(11) 14.0894(16) 78.847(8) 76.488(8) 83.226(8) 991.91(19) 2 416 1.327 0.089 multiscan 0.9477 0.9938 52.92 13608 4063 2561 (−9, 9), (−11, 12), (−17, 17) 0.0600 274 0.0531 0.1307 0.0962 0.1537 1.009 0.28, −0.27 981200

Form1II

Form1III

Form2I

Form2II

C26H20O4, 396.42 0.50 × 0.46 × 0.18 90(2) triclinic P1̅ 9.291(3) 14.942(5) 16.170(7) 62.641(14) 84.78(2) 78.439(16) 1953.4(12) 4 832 1.348 0.090 multiscan 0.9562 0.9839 56.00 26359 9409 8219 (−11, 12), (−18, 19), (−19, 21) 0.0251 554 0.0464 0.1090 0.0542 0.1131 1.061 0.43, −0.28 981201

C26H20O4 396.42 0.65 × 0.31 × 0.31 90(2) triclinic P1̅ 9.3443(3) 16.1556(6) 27.5703(10) 103.508(2) 97.293(2) 94.867(2) 3985.8(2) 8 1664 1.321 0.089 multiscan 0.9447 0.9731 65.32 77802 28229 20967 (−13, 14), (−20, 24), (−41, 28) 0.0357 1124 0.0738 0.1740 0.1019 0.1859 1.123 0.93, −0.59 981202

C26H20O4 396.42 0.57 × 0.41 × 0.37 150(2) monoclinic P21/c 9.4399(4) 11.6282(5) 18.4041(8) 90 91.950(2) 90 2019.03(15) 4 832 1.304 0.087 multiscan 0.954 0.968 56.68 18396 5028 4193 (−12, 11), (−15, 15), (−24, 24) 0.0269 351 0.0418 0.1007 0.0517 0.1063 1.028 0.27, −0.21 981204

C26H20O4 396.42 0.65 × 0.49 × 0.33 296(2) monoclinic P21/c 9.5225(19) 9.7615(19) 23.318(4) 90 99.454(13) 90 2138.1(7) 4 832 1.232 0.083 multiscan 0.9483 0.9733 56.36 18618 5152 2755 (−11, 12), (−11, 12), (−30, 30) 0.1093 274 0.0626 0.1617 0.1176 0.1941 1.050 0.27, −0.25 981203

3 C26 H20 O4 396.42 0.46 × 0.25 × 0.24 150(2) orthorhombic P212121 3.8513(2) 21.0936(10) 23.5133(9) 90 90 90 1910.17(15) 4 832 1.378 0.092 multiscan 0.9587 0.9782 56.54 16569 4594 3974 (−5, 5), (−24, 28), (−31, 26) 0.0474 351 0.0523 0.1098 0.0636 0.1145 1.091 0.22, −0.28 981205

Figure 3. (A) ORTEP of molecule A of Form 1II crystals displaying intramolecular C−H···π interactions. The displacement ellipsoids are drawn at 50% probability level, and H atoms are shown as small spheres of arbitrary radii. (B) Structure overlay of molecules in the three polymorphs of 1 (red − Form 1I, blue − Form 1II(A), purple − Form 1II(B), green − Form 1III(A), light green − Form 1III(B), orange − Form 1III(C), gray − Form 1III(D).

them to be the conformational polymorphs.6f,15 These conformational polymorphs could be characterized by three torsion angles τ1, τ2, and τ3 (for C2−O-toluoyl group) and τ1’, τ2’ and τ3’ (for C3−O-toluoyl group; see Figure 1). Although all the torsions indicate a major difference in the orientation of molecules in polymorphs of 1, τ1 and τ2 displayed significant rotational changes leading to conformational switching. Moreover, symmetry independent molecules (A and B) in the asymmetric unit of Form 1II crystal exhibit significant

the unit-cell dimensions of the three polymorphs results in onedimensional isostructurality (except for toluoyl group orientation) in the organization of molecules (see below).6g In the molecule labeled as trailer A and trailer D (see below) in Form 1II and Form 1III crystals, respectively, both the toluoyl groups display intramolecular C−H···π interactions (Figure 3A). Structure overlay of molecules of Form 1I, Form 1II, and Form 1III crystals revealed a significant difference in the torsion angles (SI, Table S1) of toluoyl groups (Figure 3B) confirming C



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Figure 4. Similarity in the organization of the molecules to generate 1D layer in polymorphs of 1; (A) Form 1I, (B) Form 1II crystals (for organization in Form 1III crystals, see SI, Figure S11). In Form 1I crystals (A) the 1D molecular chain along the a-axis is formed via two short and linear C−H···O interactions, C22−H22···O3 (i) and C26−H26C···O4 (ii). In Form 1II crystals (B) the 1D molecular string is generated by aggregation of two symmetry independent molecules A (gray) and B (light gray) alternately via four C−H···O [one trifurcated C−H···O interaction with O3B as acceptor; C16A−H16A···O3B (i), C18A−H18C···O3B (ii), C26A−H26A···O3B (iii), and C26B−H26E···O4A (iv)] and one C−H···π [C21B−H21B···Cg2 (v)] interactions.

Figure 5. Association of 1D chains to yield isostructural bilayer in (A) Form 1I and (B) Form 1II crystals; Form 1III crystal also forms similar 1D bilayer assembly (SI, Figure S12). In Form 1I crystals, 1D bilayer is formed via linking of 1D molecular chains centrosymmetrically through excellent C8−H8···π (Cg3, (i) interaction. In Form 1II crystal, the neighboring 1D chains are joined firmly via two C−H···O interactions [C14A−H14A··· O4B (i) and C16B−H16B···O3A (ii)] and an off-centered C−H···π interaction [C8B−H8B···π (Cg7, (iii)].

difference for τ1, while values of τ2 and τ3 are comparable. In Form 1III crystal, all the torsion angles show considerable change. The conformation of the molecules as observed in all the crystal forms (SI, Figure S10) reveals that at least one of the toluoyl groups is perpendicular to the naphthalene plane. The other toluoyl group which is in the plane of the naphthalene ring is engaged in intramolecular C−H···π interaction with the perpendicularly orientated toluoyl group, e.g., molecule A (Form 1II, Figure 3A) and molecule D (Form 1III, SI, Figure S10H). The perpendicularly orientated toluoyl group either functions as a donor (molecule B, Form 1II) or acceptor (Form 1I and molecule C, Form 1III) in intermolecular C−H···π

interactions with the naphthalene ring. However, in Form 1III crystals (molecules A and B) this toluoyl group is engaged in C−H···O interactions. The toluoyl group which deviates from the perpendicular approach toward the naphthalene ring is involved in C−H···O and/or in C−H···π interactions. Because of the nonexistence of classical H-bond forming functional groups in these toluates, opportunistic weak interactions such as C−H···O, C−H···π, and π···π dominate the crystal packing in all the crystal forms.7,16,17 A common feature observed in all the polymorphs of 1 is the formation of isostructural 1D molecular strings,18 if the relative orientation of the toluoyl groups (Figure 4) is ignored. The latter causes a significant difference in stitching of molecules D



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Figure 6. Different stitching of the 1D bilayers to yield 2D bilayer in (A) Form 1I and (B) Form 1III crystals. Structure of 2D bilayers in Form 1II crystals (SI, Figure S13) is similar to Form 1I crystals. In Form 1I crystals, the 1D bilayers are weaved centrosymmetrically via C6−H6···O4 (i) interactions (SI, Table S2, entry 3), whereas in Form 1III crystal the 1D bilayers of molecules AC and BD are linked in a pseudomirror fashion via C5D−H5D···O4C (i), C5C−H5C···O4B (ii), and C4D−H4D···π (Cg14), (iii) interactions (SI, Table S2, entries 30, 36, 38). Color code for C atom: gray−molecules A, light gray−molecules C, pink−molecules B, green−molecules D (Form 1III crystals).

These isostructural 1D chains are woven centrosymmetrically in a similar fashion in their crystal lattice, to generate 1D bilayers, although with different intermolecular interactions owing to different orientations of the toluoyl groups. In Form 1I crystals, these 1D molecular chains are bridged centrosymmetrically via excellent C−H···π interactions to yield a bilayer (Figure 5A and SI, Table S2, entry 4). In Form 1II crystals (Figure 5B), the neighboring 1D chains are connected firmly via two C−H···O, an off-centered C−H···π interactions (SI, Table S2, entries 9, 10, 15) and many van der Waals forces to produce a bilayer similar to that in Form 1I crystals. Along the bilayer, both molecules A and B form their respective centrosymmetric dimers, however with different interactions due to significant difference in toluoyl group conformation (SI, Table S1). Molecule A forms centrosymmetric dimers through hydrophobic forces whereas molecules B form centrosymmetric dimeric motif through off-centered C−H···π interaction (SI, Table S2, entry 15). In Form 1III crystals (SI, Figure S11), 1D chain assemblies produced separately by molecules AC and BD also form similar respective centrosymmetric dimeric assemblies AA, BB, CC, and DD via C−H···O, off-centered C−H···π and van der Waals forces yielding two different 1D bilayers,

along these 1D strings. In Form1I crystal, the 1D molecular chain along the a-axis is formed via two short and linear C−H··· O interactions (SI, Table S2, entries 1 and 2) involving C−H of the C2-O-toluoyl group and both carbonyl oxygens O3 and O4 (Figure 4A). In Form 1II crystal also molecules form similar 1D chain along the bc diagonal but with a difference (Figure 4B). The molecular chain is generated by aggregation of two symmetry independent molecules labeled as trailer A and B alternately via four C−H···O interactions and one off-centered C−H···π interactions (SI, Table S2, entries 5−8, 17). In Form 1III crystal (containing four symmetry independent molecules), the molecules pair up, generating two different 1D molecular strings, as in Form 1II crystals; molecules labeled as trailer A and C as well as molecules B and D generate their respective 1D molecular chains (SI, Figure S11). Four C−H···O and an edge centered C−H···π interactions (SI, Table S2, entries 20, 22, 24, 25, 42) help to associate molecules in the 1D chain made by molecules A and C, whereas four C−H···O and an offcentered C−H···π interactions (SI, Table S2, entries 29, 33, 34, 37, 43) link the molecules B and D to generate another 1D molecular string. E



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energies for short and linear C−H···O interactions lie in the range of −21 to −23 kJ mol−1 in polymorphs of 1. The interaction energies of each C−H···O and C−H···π contacts however could not be computed individually. Using UNI force field computations, approximate energies for the intermolecular potential (sum of Coulombic, polarization, dispersion, and repulsion terms as defined in the PIXEL method21 and integrated in the program Mercury22) were estimated (SI, Table S3). The intermolecular potentials associated with the molecules engaged in 1D layer, 1D bilayer, and 2D bilayer formation were calculated. Averaging of intermolecular potentials found along these layers suggests that molecular aggregation generating 1D layer (Figure 4) has the strongest association between molecules in the three crystal forms, and linking of these 1D layers to form 1D bilayers (Figure 5) is the second strongest association. The intermolecular potential for the bridging of neighboring 1D bilayers to yield 2D bilayers (Figure 6) is the weakest in Form 1I and Form 1II crystals, but in Form 1III crystals it is comparable to the intermolecular potentials found along 1D bilayers. Intermolecular interactions in polymorphs of 1 were quantified via Hirshfeld surface analysis23 (SI, Figure S16) using CrystalExplorer.24 All the intermolecular interactions involved in crystals of 1 were evaluated with respect to their contribution to the overall stability of the crystal structure. Hirshfeld surfaces and fingerprint plots were also generated for the polymorphs to evaluate their differences. Among all the interactions present, H···H, C−H···O, and C−H···π made major contributions to the Hirshfeld surface areas (Figure 7).

similar to Form 1II crystals (SI, Table S2, entry 39, 40). The 1D chains of molecules A and C as well as B and D are also connected to each other across the inversion center through C−H···O (SI, Table S2, entries 23, 26, 32) and van der Waals forces to attain tight binding along the bilayer. From the above discussion, it is clear that in Form 1I crystals, the 1D chains are stitched centrosymmetrically only via C−H···π interactions, whereas in Form 1II and Form 1III crystals the 1D chains are linked through C−H···O and C−H···π interactions, thus providing tight binding of the 1D chains. Differences in Stitching of Bilayers. Although the molecules in Form 1I, Form 1II, and Form 1III crystals revealed isostructural arrangements in the form of 1D bilayers and these 1D bilayers weaved in the same fashion in Form 1I and Form 1II crystals (Figure 6A), Form 1III crystals showed a different mode of cohesion (Figure 6B). In Form 1I and Form 1II crystals, the adjacent 1D bilayers are stitched in an antiparallel fashion to yield the 2D bilayer assembly although with different intermolecular interactions. Centrosymmetric C−H···O interactions bridged the 1D bilayers in Form 1I crystals (Figure 6A and SI, Table S2, entry 3), whereas the dimeric C−H···π interactions weaved the 1D bilayers in Form 1II crystals (SI, Figure S13, and Table S2, entry 19). However, in Form 1III crystals, the association of 1D bilayers generated by molecules AC and BD is quite different to yield a 2D layered structure along the c-axis (Figure 6B). Molecular Packing in Other Directions. Molecular packing in Form 1I, Form 1II, and Form 1III crystals also seemed to be grossly similar in all directions (SI, Figure S14). The 2D bilayer assemblies in Form 1I crystals are loosely connected via van der Waals forces to generate a layered structure. Formation of parallel separate alternate layered assemblies of molecules A and B along the c-axis was observed in Form 1II crystals, while similar aggregation of molecules AD and BC was seen in Form 1III crystals along the b-axis. Molecular packing (SI, Figure S15A) along the ab diagonal in Form 1I crystals revealed association of C−H···π linked dimeric units through C−H···O interactions to generate a 2D layered structure. In Form 1II crystals, dimeric assemblies of molecules A as well as B are linked centrosymmetrically with the respective dimeric units generating parallel layers along the bc diagonal, which are interlinked through C−H···O and C−H···π interactions. In Form 1III crystals, the alternate aggregation of dimers of molecules A and D generate a layer parallel to the layer comprised of alternate dimers of molecules C and B through C−H···O and C−H···π interactions. The loss of center of inversion between the dimeric motifs of molecules A and D as well as molecules B and C in Form 1III crystals seem to be due to significant conformational change of toluoyl groups resulting in four symmetry independent molecules. In Form 1II crystals molecules A and D as well as molecules B and C have the same conformation; hence there are only two symmetry independent molecules in its asymmetric unit. The computation of lattice energies for the trimorphs of 1 (Oprop module of the OPiX program suite19) by summation of atom−atom pairwise potential energies (described by the UNI force field20) revealed the values of −208.9, −213.6, and −202.6 kJ mol−1 for Form 1I, Form 1II, and Form 1III crystals, respectively, indicating that the Form 1II crystals are most stable and Form 1III crystals are least stable. The values of crystal densities 1.327 g cm−3 (Form 1I), 1.348 g cm−3 (Form 1II), and 1.321 g cm−3 (Form 1III) are consistent with the calculated lattice energies. The intermolecular interaction

Figure 7. Contribution of various interactions to Hirshfeld surfaces areas in crystals of 1, 2, and 3.

In polymorphs of 1 the contribution of H···H contacts is the maximum and lay in the range 40−45%, perhaps due to aggregation of molecules via hydrophobic interactions. The center spike in all the 2D fingerprint plots corresponds to the H···H contact. The second major contribution to the Hirshfeld surface areas come from C−H···π interactions (∼37%), which is almost double as compared to C−H···O interactions (18%), thus confirming their profound influence in the crystal packing of all the polymorphs of 1. The C−H···π and the C−H···O intermolecular interactions appear as a pair of spikes in symmetric fashion in 2D fingerprint plots (end spikes for C− H···π and midway sharp spikes for C−H···O contacts, SI, Figure S16). Implications for the Mechanism of Phase Transformation from Comparison of Molecular Packing. Although it is difficult to specify the mechanistic pathways involving precise molecular movements for the conversion of F



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Figure 8. Topological patterns of the molecular organization during phase transition, (A) 2D layer assembly formed by linking of 1D bilayers in centrosymmetric fashion in Form 1I crystals; (B) 2D layer assembly formed by linking of 1D bilayers comprising of two symmetry independent molecules in centrosymmetric fashion in Form 1II crystals; (C) resulting packing pattern due to noncrystallographic rotation of every second 1D bilayer by 180° and generation of pseudomirror symmetry as in Form 1III crystals.

between them represents the inversion center. The conversion of Form 1I and Form 1II crystals to Form 1III crystal involves noncrystallographic 180° rotation of every alternate 1D bilayer, perpendicular to their plane, to generate a mirror plane between them and the adjacent bilayers remaining motionless. Such rotation is possible because of their loose association with each other which allows the needed conformational changes in the toluoyl groups. These molecular rearrangements result in a new set of weak interactions for stabilizing the structure in the newly formed crystal lattice but destroy the transient mirror symmetry between the 1D bilayers. These molecular movements also result in generating new symmetry independent molecules having a different conformation in the new crystal lattice. The results pertaining to the polymorphism of the paratoluate 1 described so far suggest that transformation of Form 1I and Form 1II crystals to Form 1III crystals on the whole is associated with an increase in disorder and decrease in lattice energy. Hence, these changes can be viewed as the transformation of a stable crystalline phase to a metastable crystalline phase during the conversion of a solid phase, Form 1I and Form 1II to Form 1III which is an intermediate phase. This is also supported by a decrease in the density of crystals across Form 1I, Form 1II, and Form 1III, which is reflected in less efficient packing of molecules in the latter as compared to the former two crystals. The metastable nature of Form 1III crystals is evident from the crystallization experiment which produced only Form 1I and Form 1II crystals from almost all the trials barring one which yielded Form 1III crystals. Invoking the principle of microscopic reversibility for these processes implies that Form 1III crystals could be an intermediary stage during the formation of Form 1I and Form 1II crystals. This is analogous to the involvement of intermediates during chemical reactions that involve formation of new covalent bonds. Hence we believe study of the structure of metastable or transient crystals (observed during the formation of stable crystals) aid in unraveling the process of crystallization. Polymorphs of the meta-Ditoluate 2. Among the two types of crystals obtained from the m-toluate 2, Form 2I crystals (plates) were stable while Form 2II crystals (needles) lost crystallinity rapidly under ambient conditions. This suggested that the Form 2II crystals were metastable and perhaps appear under kinetically controlled conditions, while plates were produced under thermodynamic conditions. The loss of crystalline nature in Form 2II crystals began at one end of the needle and progressed to the other end. DSC analysis (Figure S7B, SI) revealed two endotherms for Form 2II crystals

Form 1I and Form 1II crystals to Form 1III crystal, some clues can be obtained from a comparison of the packing of molecules in the three crystal forms. Since Form 1I and Form 1II crystals are formed solely via weaker intermolecular interactions, they tend to loosen in the lattice near the transition temperature to allow the rearrangement of molecules as in Form 1III crystal via relevant weak interactions.6a,c,9,25 In Form 1III crystals, molecules AC and BD generate separate 1D bilayers through C−H···O and C−H···π interactions (SI, Figure S12) revealing tighter binding of molecules along theses bilayers compared to Form 1I crystal but similar to Form 1II crystal. The significant difference between these structures is the stitching of these 1D bilayers to produce 2D bilayer structure as discussed earlier. In Form 1I and Form 1II crystals, although the 1D bilayers are bridged centrosymmetrically (Figure 6A and SI, Figure S13) these interactions are not strong enough to hold the 1D bilayers tightly at high temperatures, and they rearrange into the Form 1III crystals. The conversion of Form 1I crystals to Form 1III crystals at lower temperature (117 °C) as compared to Form 1II crystals (134 °C) can be attributed to the relatively tighter binding of molecules along the 1D bilayer structure in Form 1II crystals than in Form 1I crystals (Figure 5). The toluoyl groups along the 1D bilayer in Form 1I and Form 1II crystals are required to reorient themselves by ∼80−150° to achieve tight association as observed in Form 1III crystals. Hence the relatively weaker association of the 1D bilayers in Form 1I and Form 1II crystals seem to be responsible for their transformation to Form 1III crystals at high temperature, perhaps through highly disordered phases, since multiple crystalline domains (Form 1III crystals) are formed from a single crystal (of Form 1I or Form 1II). These crystal-to-crystal thermal phase transformations6d,9,26 suggest concerted and cooperative movement of groups of molecules in the crystalline state. However, the overall changes during the phase transition are far too large (and hence irreversible) and result in the fragmentation of the Form 1I and Form 1II crystals. This is in contrast to molecular movements in reversible phase transitions which involve minimum molecular motion and hence are restorable.14,27 Careful inspection of the packing patterns of these 1D bilayers revealed that they are closely related (irrespective of the orientation of the toluoyl groups) and differ by only one or two rotation of common motifs, i.e., “centrosymmetric dimers” (morphotrops), thus making it an excellent case of morphotropism.28,29 To visualize these changes, a cartoon representation of the molecular packing pattern is shown in Figure 8. Each centrosymmetric dimeric unit is represented by filled and open circle with two appendages; a tiny open circle (red) G



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Figure 9. Molecular assembly in Form 2I (A, B) and Form 2II (C, D) crystals. (A) Molecular organization along the a-axis revealing formation of zero-dimensional synthons through bifurcated C4−H4···O3 (i), C5−H5···O3 (ii), and C21−H21···Cg2 (iii) interactions and aggregation along the b-axis via bifurcated C17−H17···O4 (iv) and C18−H18A···O4 (v) interactions forming 1D layer. These c-glide related 1D layers are loosely joined along the c-axis via C23−H23···O3 (vi) interaction, yielding 2D layered structure on the bc plane. (B) View of the molecular packing on ac plane showing weaving of dimeric synthons through C−H···π [C13−H13···Cg2 (i) and C15−H15···Cg4 (ii)] and marginal π···π (iii) interactions along aaxis and via C23−H23···O3 (iv) interaction along the c-axis. (C) View of the molecular packing down the a-axis in Form 2II crystals displaying helical arrangement of molecules through C8−H8···O3 (i) and C−H···π [C21−H21···Cg1 (ii)] interactions. These adjacent helical assemblies are linked along the c-axis via C26−H26B···O1 (iii) and C−H···π [C26−H26C···Cg4 (iv)] interactions. (D) View of the molecular packing down the helical axis showing joining of “dancing pairs” through C26−H26B···O1 (i) and marginal C−H···π [C13−H13···Cg2 (ii)] interactions (along the caxis).

and one endotherm for Form 2I crystals. The first endotherm observed for Form 2II crystals indicated a structural phase transition. PXRD analysis (Figure S8B) of this process confirmed the thermal conversion of Form 2II crystals to Form 2I crystals. Toluoyl groups in both forms adopt an extended conformation (SI, Figure S17A), which forbids intramolecular interactions between them (SI, Figure S10I−J). Structure overlay of molecules (SI, Figure S17B) in both the polymorphs of 2 revealed only slight changes (unlike in polymorphs of the p-toluate 1) in the conformation of the molecules indicating the possibility of packing polymorphism. Molecules in Form 2I crystals are packed compactly due to C−H···O and C−H···π interactions. Although Form 2I crystals belong to P21/c space group, the closely associated molecules form zero-dimensional centrosymmetric dimeric synthon (Figure 9A) through bifurcated C−H···O and off-centered C−H···π interactions (SI, Table S2, entries 45, 46, 52) rather than assembling helically along the crystallographic 2-fold screw axis (b-axis). These dimeric motifs are unit-translated in centrosymmetric fashion to generate a 1D layered structure along the b-axis via bifurcated (three-centered) C−H···O

interactions (SI, Table S2, entries 47, 48). These adjacent 1D layers are joined through short but nonlinear C−H···O interaction (SI, Table S2, entry 49) along the direction of the c-axis, yielding a 2D network (Figure 9A). Molecular packing viewed down the 1D layer (b-axis) revealed the linking of dimeric motifs in centrosymmetric fashion via two off-centered C−H···π (SI, Table S2, entries 50, 51) and marginal π···π interaction involving phenyl rings of toluoyl groups, producing another 1D layer structure along the c-axis. These adjacent 1D layers are loosely connected via C−H···O interaction to yield a 2D layer assembly (Figure 9B and SI, Table S2, entry 49). In contrast, molecules in Form 2II crystal which belong to P21/c space group assemble helically along the crystallographic 2-fold screw axis via somewhat long but linear C−H···O and marginal C−H···π interactions (SI, Table S2, entries 53, 55). Adjacent helices along the c-axis are held to each other via long C−H···O and short C−H···π interactions (Figure 9C and SI, Table S2, entries 54, 56). A view down the helical axis (b-axis) reveals a pairwise association of molecules akin to “dancing pairs” (Figure 9D). The adjacent “dancing pairs” are loosely connected along the c-axis via long C−H···O and off-centered C−H···π contacts (SI, Table S2, entries 54, 57) and exclusively H



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via weak hydrophobic forces along the a-axis. This arrangement of “dancing pairs” brings the polar segment of neighboring molecules in close association generating a hydrophilic layer between the hydrophobic layers formed by the toluoyl and naphthalene rings. Although molecules have equal opportunities to engage via good C−H···O and C−H···π interactions (as seen in Form 2I crystals), surprisingly none of the carbonyl groups take part in any significant interaction resulting in a fragile lattice which could be the reason for its instability. The computation of lattice energies for the dimorphs of 2 gave the values of −205.0 and −195.2 kJ mol−1 for Form 2I and Form 2II, respectively, indicating that the Form 2I crystals are more stable. The values of crystal densities 1.304 g cm−3 (Form 2I) and 1.232 g cm−3 (Form 2II) are consistent with the lattice energies. This also substantiates the formation of Form 2I crystals exclusively in all the crystallization experiments. Transformation of Form 2II to Form 2I crystals under ambient conditions could be due to the reorganization of a metastable (crystalline) assembly of molecules to a stable crystalline phase. The intermolecular interaction energy for short and linear C− H···O interactions was estimated to be −20 to −21 kJ mol−1. The intermolecular potential between the molecules were also estimated (SI, Table S4) to get clues about the incipient molecular aggregation at the nucleation event. However, similar intermolecular potential values for the 1D layer assemblies formed by association of “zero-dimensional” molecular synthons either by bifurcated C−H···O interactions (Figure 9A) along the b-axis, or by C−H···π and π···π interactions (Figure 9B) along the a-axis preclude determination of the sequence of growth of different layers in Form 2I crystals. These 1D layer assemblies then could have bridged via short but nonlinear C23−H23···O3 interactions to result in the 3D structure. In Form 2II crystals also, helical association of molecules (Figure 9C) have a higher intermolecular potential value compared to the aggregation of these neighboring helices, suggesting formation of helical assemblies and subsequent aggregation of these helices (Figure 9D). The quantification of the intermolecular interactions via Hirshfeld surface analysis (SI, Figure S16G−J) revealed maximum contribution from H···H contacts (45% for Form 2I and 44% for Form 2II crystals, Figure 7). The second major contribution to the Hirshfeld surface areas come from C−H···π interactions (36% for Form 2I and 37% for Form 2II crystals) which is almost double that of C−H···O interactions (16% for Form 2I and 18% for Form 2II crystals), thus confirming their profound influence in the crystal packing. However, it must be noted that these percentage contributions do not differentiate between close and distant contacts. Implications for the Mechanism of Phase Transformation from Comparison of Molecular Packing. From the similar packing views (down b-axis in Form 2II and down c-axis in Form 2I crystals, Figure 10), possible molecular movements during the polymorphic phase transitions can be envisaged. In Form 2II crystals, the centrosymmetrically related molecules of adjacent helices are loosely connected via weak C26−H26B···O1 and hydrophobic forces along c and a-axis respectively (Figure 10A), whereas in Form 2I crystals, the zero-dimensional dimeric synthons are tightly held along the baxis through bifurcated short and linear C−H···O as well as moderate C−H···π interactions along the a-axis (Figure 10B). This change at the dimeric motifs subsequently breaks the other interactions involved in the helix formation. Hence, it appears that during the phase transition the molecules sacrifice

Figure 10. Views of packing of molecules in the dimorphs of 2 suggesting the possible changes during transformation. (A) “Closing in” of molecules in Form 2II crystals toward each other (shown by arrows) by ca. 0.6 Å (along the b-axis) and 3.2−3.9 Å (along the aaxis). (B) Compact packing achieved through various C−H···O [C4− H4···O3 (i), C5−H5···O3 (ii), C17−H17···O4 (iv), C18−H18A···O4 (v)] and C−H···π [C21−H21···π (iii), C13−H13···π (vi) C15− H15···π (vii)] interactions in Form 2I crystals.

weak contacts in Form 2II crystals (Figure 10A) to attain stronger contacts in Form 2I crystals (Figure 10B). The disintegration of Form 2II single crystals to microcrystalline Form 2I crystals could be because of these large molecular movements in the crystal lattice. Crystal Structure of the ortho-Ditoluate 3. Crystallization of the o-ditoluate 3 under a variety of conditions and different solvents (with an intention to obtain metastable crystals) yielded fibrous chiral crystals belonging to the orthorhombic space group P212121 with one molecule in the asymmetric unit. The chirality of crystals of the o-ditoluate 3 can be attributed to the helical arrangement of molecules throughout the lattice rather than configurational or conformational30 chirality of individual molecules.6b,31 DSC analysis of crystals of 3 showed only the melting endotherm indicating no phase transition before melting (SI, Figure S7C). The conformation of the molecules as observed in the crystal structure (SI, Figure S18) revealed that the toluoyl groups make roughly equal angle (∼37°) with the basal plane of the naphthalene ring. The orientation of the toluoyl groups in opposite directions with respect to each other precludes the possibility of intramolecular interactions between them. I



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Figure 11. (A) Molecular packing viewed down the a-axis showing flat helical association of molecules through C23−H23···O3 (i) interactions which are in turn linked via C6−H6···O4 (ii) contact to generate a 2D corrugated pattern. (B) Catemeric association of molecules facilitating π···π stacking interactions [(i) Cg1···Cg1, (ii) Cg2···Cg2, (iii) Cg3···Cg3, (iv) Cg4···Cg4 and (v) C6−H6···O4] between the unit-translated molecules along the a-axis.

Molecules of 3 form flat helical chains along the crystallographic 2-fold screw axis exclusively via C−H···O interactions (Figure 11A and SI, Table S2, entry 58). Neighboring helical chains are stitched in an antiparallel fashion via C−H···O interactions (SI, Table S2, entry 59) to generate corrugated 2D assembly along the a-axis (Figure 11A). Molecular packing viewed down the b-axis revealed formation of zigzag helical pattern along the a-axis (Figure 11B) wherein benzene rings of unit translated molecules along the helix are engaged in aromatic π···π stacking interactions (SI, Table S2, entries 60− 67) which could have played a major role in producing chiral crystal packing.32 The chiral packing in crystals of the o-dioluate 3 could also have resulted from the presence of methyl group at the ortho position which restricts rotation along the C−C and the C−O bonds.33 The lattice energy calculations for the crystal of 3 revealed a value of −216.8 kJ mol−1, which indicated that it is the most stable crystal form among all the crystal forms of toluates 1−3. Calculation of the interaction energies for C6−H6···O4 (Figure 11A) contact gave a value of −21.2 kJ mol−1. The assessment of intermolecular potential associated with the unit-translated molecules linked via aromatic π···π stacking interactions along the helical chain (a-axis) was found to be −118.8 kJ mol−1 (Figure 11B), and this probably contributed to the helical assembly of molecules leading to a chiral crystal. The estimation of intermolecular potential between the molecules associated helically via C6−H6···O4 and C23−H23···O4 interactions (along the c- and b-axis respectively) gave the values of −21.9 and −18.6 kJ mol−1, respectively. The values of intermolecular potentials reveal the collective strength of π···π interactions in molecular organization as compared to C−H···O interactions. The Hirshfeld surface analysis (Figure 7) showed a major contribution from H···H contacts (57%), maximum among all the interactions. The contribution to the Hirshfeld surface areas from C−H···π (15%) and π···π (14%) interactions is almost similar, whereas the contribution from C−H···O interactions is just 8%. This indicates significant contribution from π···π interactions in the o-ditoluate 3 which was found to be negligible in polymorphs of p-ditoluate 1 and m-ditoluate 2, whereas involvement of C−H···π and C−H···O interactionsis approximately halved in the o-ditoluate 3 (SI, Figure S16 K, L for Hirshfeld surfaces and fingerprint plot).

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CONCLUSIONS

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ASSOCIATED CONTENT

The para- and meta-ditoluates 1 and 2 exhibited conformation and packing polymorphism, respectively, while crystals of orthoditoluate 3 yielded a chiral crystal form. The crystallization experiments confirmed the relative stability of polymorphs of 1 (Form 1II > Form 1I > Form 1III) and 2 (Form 2I > Form 2II), and the same is consistent with their lattice energies. The polymorphic behavior of 1 and 2 can be attributed to the intrinsic conformational flexibility of molecules that generates different pattern of intermolecular weak interactions, e.g., C− H···O and C−H···π. This suggests that the differences between the crystal structures of isostructural polymorphs and the transitions among them could be well understood from the studies of morphotropism.26,27 The increasing number of polymorphs on going from ortho- to meta- to para-toluate corresponds well with the number of noncovalent interactions made by the terminal phenyl rings in their crystals. These results also confirmed the general trend of crystals having more number of molecules in the asymmetric unit (Z′ > 1) being less stable relative to their low Z′ crystals.34

S Supporting Information *

Experimental details for the preparation of 2 and 3; 1H and13C NMR spectra of 2 and 3; X-ray crystallography; DSC analysis; powder X-ray diffraction studies; hot stage microscopy (HSM) studies. Figures for (a) intramolecular geometry of molecules in polymorphs of 1 and 2; (b) the formation of 1D layer in Form 1III crystals; (c) the formation 1D bilayer in Form 1III crystals; (d) stitching of 1D bilayers in Form 1II crystals to generate 2D bilayer; (e) molecular packings in Form 1I, Form 1II and Form 1III in other directions; (f) Hirshfeld surfaces and fingerprint plots for crystals of 1−3, and (g) ORTEPS and molecular overlay diagrams for crystals of 2−3. Tables of (a) torsion angles (deg) for polymorphs of 1; (b) geometrical parameters of intermolecular interactions in polymorphs of 1 and 2 and in crystals of 3; (c) intermolecular potential energies for polymorphs of 1 and 2. This material is available free of charge via the Internet at http://pubs.acs.org. J



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Bhadbhade, M. M.; Shashidhar, M. S. CrystEngComm 2010, 12, 478− 484. (10) (a) Krishnaswamy, S.; Shashidhar, M. S.; Bhadbhade, M. M. CrystEngComm 2011, 13, 3258−3264. (b) Tamboli, M. I.; Krishnaswamy, S.; Shashidhar, M. S.; Gonnade, R. G. Chem.Eur. J. 2013, 19, 12867−12874. (11) Nakamatsu, S.; Yoshizawa, K.; Toyota, S.; Toda, F.; Matijasic, I. Org. Biomol. Chem. 2003, 1, 2231−2234. (12) Verma, A. R.; Krishna, P. Polymorphism and Polytypism in Crystals; John Wiley: New York, 1966; pp 15−30. (13) (a) Kobayashi, K.; Sato, A.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 2003, 125, 3035−3045. (b) Parmar, M. M.; Khan, O.; Seton, L.; Ford, J. L. Cryst. Growth Des. 2007, 7, 1635−1642. (c) Musumeci, D.; Hunter, C. A.; McCabe, J. F. Cryst. Growth Des. 2010, 10, 1661−1664. (14) Dunitz, J. D.; Bernstein, J. Acc. Chem. Res. 1995, 28, 193−200. (15) Seethalekshmi, S.; Guru Row, T. N. Cryst. Growth Des. 2012, 12, 4283−4289. (16) Nishio, M.; Umezawa, Y.; Honda, K.; Tsuboyama, S.; Suezawa, H. CrystEngComm. 2009, 11, 1757−1788. (17) Tiekink, E. R. T.; Zukerman-Schpector, J. The Importance of PiInteractions in Crystal Engineering: Frontiers in Crystal Engineering; Wiley-VCH: Chichester, UK, 2012. (18) (a) Anthony, A.; Nangia, A.; Desiraju, G. R.; Jaskólski, M. Chem. Commun. 1998, 2537−2538. (b) Fábián, L.; Argay, A.; Kálmán, A.; Báthori, M. Acta Crystallogr. Sect. B 2002, 58, 710−720. (c) Fábián, L.; Kálmán, A. Acta Crystallogr. Sect. B 2004, 60, 547−558. (d) Bhosekar, G. V.; Murali, C.; Gonnade, R. G.; Shashidhar, M. S.; Bhadbhade, M. M. Cryst. Growth Des. 2005, 5, 1977−1982. (19) Gavezzotti, A. OPiX, A Computer Program Package for the Calculation of Intermolecular Interactions and Crystal Energies; University of Milano, October 2007. (20) (a) Filippini, G.; Gavezzotti, A. Acta Crystallogr. Sect. B: Struct. Sci. 1993, 49, 868−880. (b) Gavezzotti, A.; Filippini, G. J. Phys. Chem. 1994, 98, 4831−4837. (21) Gavezzotti, A. Acc. Chem. Res. 1994, 27, 309−314. (22) Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Rodriguez-Monge, L.; Taylor, R.; van de Streek, J.; Wood, P. A. J. Appl. Crystallogr. 2008, 41, 466−470. (23) (a) McKinnon, J. J.; Spackman, M. A.; Mitchell, A. S. Acta Crystallogr. Sect. B 2004, B60, 627−668. (b) McKinnon, J. J.; Jayatilaka, D.; Spackman, M. A. Chem. Commun. 2007, 3814−3816. (c) Spackman, M. A.; Jayatilaka, D. CrystEngComm. 2009, 11, 19−32. (24) Wolff, S. K.; Grimwood, D. J.; McKinnon, J. J.; Jayatilaka, D.; Packman, M. A. Crystal Explorer; University of Western: Perth, Australia, 2007; http://hirshfeldsurface.net/CrystalExplorer. (25) (a) Munshi, P.; Venugopala, K. N.; Jayashree, B. S.; GuruRow, T. N. Cryst. Growth Des. 2004, 1, 1105−1107. (b) Gonnade, R. G.; Shashidhar, M. S.; Bhadbhade, M. M. CrystEngComm 2008, 10, 288− 296. (26) (a) Dunitz, J. D. Pure Appl. Chem. 1991, 63, 177−185. (b) Kaftory, M.; Botoshansky, M.; Kapon, M.; Shteiman, V. Acta Crystallogr. Sect. B 2001, 57, 791−799. (c) Omondi, B.; Fernandes, M. A.; Layh, M.; Levendis, D. C.; Look, J. L.; Mkwizu, T. S. P. CrystEngComm 2005, 7, 690−700 and references cited therein. (d) Centore, R.; Jazbinsek, M.; Tuzi, A.; Roviello, A.; Capobianco, A.; Peluso, A. CrystEngComm 2012, 4, 2645−2653. (e) Harada, N.; Karasawa, S.; Matsumoto, T.; Koga, N. Cryst. Growth Des. 2013, 13, 4705−4713. (27) (a) Hashizume, D.; Miki, N.; Yamazaki, T.; Aoyagi, Y.; Arisato, T.; Uchiyama, H.; Endo, T.; Yasui, M.; Iwasakia, F. Acta Crystallogr. Sect. B 2003, 59, 404−415. (b) Fernandes, M. A.; Levendis, D. C.; deKoning, C. B. Acta Crystallogr. Sect. B 2004, 60, 300−314 and references cited therein. (28) (a) Groth, P. Ber. Dtsch. Chem. Ges. 1870, 3, 449−457. (b) Kitaigorodskii, A. I. Organic Chemical Crystallography; Consultants Bureau: New York, 1961; pp 222−231.

AUTHOR INFORMATION

Corresponding Authors

*(R.G.G.) Fax: 91-20-25902642. Tel: 91-20-25902252. E-mail: [email protected], [email protected]. *Fax: 91-20-25902629. Tel: 91-20-25902055. E-mail: ms. [email protected]; [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS M.I.T. and S.K. thank the CSIR, New Delhi, for fellowships. We thank Mr. Mangesh Mahajan and Mr. Yogesh Marathe for recording the PXRD patterns. This work was supported by the Science & Engineering Research Board (SERB), New Delhi (Grant No. SB/S1/OC-23/2013 to M.S.S. and R.G.G.).

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REFERENCES

(1) (a) Brittain, H. G. Polymorphism in Pharmaceutical Solids; Marcel Dekker Inc.: New York, 1999. (b) Sarma, J. A. R. P.; Desiraju, G. R. In Crystal Engineering: Polymorphism and Pseudopolyorphism in Organic Crystals: A Cambridge Structural Database Study; Seddon, S. R.; Zaworotko, M. J., Eds.; Kluwer: Norwell, MA, USA, 1999; p 325. (c) Threlfall, T. Org. Process Res. Dev. 2000, 4, 384−390. (d) Bernstein, J. Polymorphism in Molecular Crystals; Oxford University Press: Oxford, UK, 2002. (2) (a) Bauer, J.; Spanton, S.; Henry, R.; Quick, J.; Dziki, W.; Porter, W.; Morris, J. J. Pharm. Res. 2001, 18, 859−866. (b) Vishweshwar, P.; McMahon, J. A.; Oliveira, M.; Peterson, M. L.; Zaworotko, M. J. J. Am. Chem. Soc. 2005, 127, 16802−16803. (c) Hilfiker, R. Polymorphism in the Pharmaecutical Industry; Wiley-VCH: Weinheim, Germany, 2006. (d) Näther, C.; Jeβ, I. Angew. Chem., Int. Ed. 2006, 45, 6381−6383. (e) Bond, A. D.; Boese, R.; Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 2007, 46, 615−417. (f) Long, S.; Parkin, S.; Siegler, M. A.; Cammers, A.; Li, T. Cryst. Growth Des. 2008, 8, 4006−4013. (3) (a) McCrone, W. C. Anal. Chem. 1950, 22, 1225−1226. (b) Brill, T. B.; Karpowicz, R. J. J. Phys. Chem. 1982, 86, 4260−4265. (c) Karpowicz, R. J.; Serglo, S. T.; Brlll, T. B. Inorg. Chem. 1983, 22, 363−365. (d) Evers, J.; Klapotke, T. M.; Mayer, P.; Oehlinger, G.; Welch, J. J. Inorg. Chem. 2006, 45, 4996−5007. (e) Fabbiani, F. P. A.; Pulham, C. R. Chem. Soc. Rev. 2006, 35, 932−942. (f) Dreger, Z. A.; Gupta, Y. M. J. Phys. Chem. A 2010, 114, 8099−8105. (4) Stockton, G. W.; Godfrey, R.; Hitchcock, P.; Mendelsohn, R.; Mowery, P. C.; Rajanand, S.; Walker, A. F. J. Chem. Soc., Perkin Trans. 2 1998, 2061−2071. (5) (a) Price, C. P.; Grzesiak, A. L.; Kampf, J. W.; Matzger, A. J. Cryst. Growth Des. 2003, 3, 1021−1025. (b) Paulus, E. F.; Leusen, F. J. J.; Schmidt, M. U. CrystEngComm 2007, 9, 131−143. (6) (a) Senthil Kumar, V. S.; Pigge, F. C.; Rath, N. P. CrystEngComm 2004, 6, 102−105. (b) Gonnade, R. G.; Shashidhar, M. S.; Bhadbhade, M. M. Chem. Commun. 2004, 2530−2531. (c) Chopra, D.; Nagrajan, K.; Guru Row, T. N. Cryst.Growth Des. 2005, 5, 1035−1039. (d) Gonnade, R. G.; Bhadbhade, M. M.; Shashidhar, M. S.; Sanki, A. K. Chem. Commun. 2005, 5870−5872. (e) Roy, S.; Banerje, R.; Nangia, A.; Kruger, G. J. Chem.−Eur. J. 2006, 12, 3777−3788. (f) Nangia, A. Acc. Chem. Res. 2008, 41, 595−604. (g) Manoj, K.; Gonnade, R. G.; Shashidhar, M. S.; Bhadbhade, M. M. CrystEngComm 2009, 11, 1022−1029. (h) Cruz-Cabeza, A. J.; Bernstein, J. Chem. Rev. 2014, 114, 2170−2191. (7) (a) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bonds: In Structural Chemistry and Biology; Oxford University Press: Oxford, NY, 1999 and references cited therein. (b) Munshi, P.; Guru Row, T. N. Crystallogr. Rev. 2005, 11, 199−241. (8) Galek, P. T. A.; Chisholm, J. A.; Pidcock, E.; Wood, P. A. Acta Crystallogr. Sect. B 2014, 70, 91−105. (9) (a) Murali, C.; Shashidhar, M. S.; Gonnade, R. G.; Bhadbhade, M. M. Chem.Eur. J. 2009, 15, 261−269. (b) Gonnade, R. G.; K



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(29) (a) Kálmán, A. Acta Crystallogr. Sect. B: Struct. Sci. 2005, 61, 536−547. (b) Kálmán, A.; Fábián, L. Acta Crystallogr. Sect. B: Struct. Sci. 2007, 63, 411−417. (30) (a) Fleischer, E. B.; Sung, N.; Hawkinson, S. J. J. Phys. Chem. 1968, 72, 4311−4312. (b) Tanatani, A.; Yamaguchi, K.; Azumaya, I.; Fukutomi, R.; Shudo, K.; Kagechika, H. J. Am. Chem. Soc. 1998, 120, 6433−6442. (31) Gurale, B. P.; Gonnade, R. G.; Shahsidhar, M. S. Acta Crystallogr. Sect. C 2012, 68, o183−o187. (32) Dureissix, V.; Sanselme, M.; Robin, Y.; Coquerel, G. Cryst. Growth Des. 2009, 9, 3438−3443. (33) Pidcock, E. Chem. Commun. 2005, 3457−3459. (34) Nangia, A. J. Ind. Inst. Sci. 2007, 87, 133−147.

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