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Colored Polymorphs: Thermochemical and Structural Features of N-Picryl-p-toluidine Polymorphs and Solvates Doris E. Braun,† Thomas Gelbrich,† Ram K. R. Jetti,† Volker Kahlenberg,‡ Sarah L. Price,§ and Ulrich J. Griesser*,†

CRYSTAL GROWTH & DESIGN 2008 VOL. 8, NO. 6 1977–1989

Institute of Pharmacy, UniVersity of Innsbruck, Innrain 52, 6020 Innsbruck, Austria, Institute of Mineralogy and Petrography, UniVersity of Innsbruck, Innrain 52, 6020 Innsbruck, Austria, and Department of Chemistry, UniVersity College London, 20 Gordon Street, London WC1H 0AJ, U.K. ReceiVed January 8, 2008; ReVised Manuscript ReceiVed February 8, 2008

ABSTRACT: An intriguing example of conformational and color polymorphism is observed in p-tolyl-(2,4,6-trinitrophenyl)-amine (picryltoluidine, PT), which forms two crystalline modifications, the red form IR and the orange form IIO. Solvated crystals with a PT/solvate ratio of 1:1 (pyridine) or 2:1 (benzene, chlorobenzene, toluene, or xylene) were obtained only from aromatic solvents, albeit with some difficulty, from aromatic solvents. The crystallization from all other tested solvents produced either a highly pure phase or a mixture of the two anhydrous forms. Single crystal structure determinations were carried out on the seven solid forms, along with a characterization by thermal analysis (hot stage microscopy, DSC, TGA), vibrational spectroscopy (IR, Raman) and X-ray powder diffraction. The PT molecules in all structures exhibit intramolecular N-H · · · O bonds. The different colors are attributed to intramolecular electronic effects due to an increased delocalization of the secondary amino nitrogen lone-pair electrons in the aromatic ring and nitro groups, rather than to differences in the intermolecular excitation. The relationships between the seven crystal structures were investigated using the program XPac. They are all composed of the same one-dimensional stack of PT molecules. All 2:1 solvates in this study are isostructural. The desolvation behavior of the pyridine solvate is explained by its very close two-dimensional packing similarity to form IR. The molecular aggregation in the solid forms of PT is discussed in terms of similar packing fragments and weak interactions (C-H · · · O, C-H · · · π contacts, and π · · · π stacking). Introduction Polymorphism, the ability of a molecule to adopt different crystal structures, provides special challenges and opportunities for chemical research and development.1 There are relatively few examples where the polymorphism of an organic substance is associated with crystalline forms of different color.2 The first examples were reported nearly 100 years ago by Hantzsch.3 This phenomenon was originally called chromoisomerism, and later the term crystallochromy was coined by Klebe et al.4 The present work describes such an example and deals with the polymorphism and solvate formation of p-tolyl-(2,4,6-trinitrophenyl)-amine, commonly called picryltoluidine (PT, Figure 1). Given that this compound exhibits conformational flexibility, it is obvious that the color changes are connected with differences in molecular conformation (conformational polymorphism) similar to the well-known case of “ROY”.1 Previous reports describe the existence of three differently colored nonsolvated polymorphic forms (red, orange, and yellow) of PT. The thermal behavior of the red and orange polymorphs was investigated by several groups.5–8 Ilynia et al.9 suggested that the “yellow form” exists as a “water-cluster” compound, since it was prepared from a water-acetone mixture. Egiazaryan et al.6 and Matevosyan et al.7 also describe the existence of a third, yellow polymorph produced by recrystallization from dichloroethane, dioxane, or benzene. However, apart from the reported heat of solution and melting point,7 there is little evidence for the actual existence of this “yellow form”. Other papers8,10,11 only mention a red and orange form. Furthermore, it has been reported that PT forms benzene solvates5 which were obtained from different starting materials * Corresponding author. E-mail: [email protected]. † Institute of Pharmacy, University of Innsbruck. ‡ Institute of Mineralogy and Petrography, University of Innsbruck. § University College London.

Figure 1. PT polymorphs and solvates examined in this study.

(red and orange forms, respectively). To date, the Cambridge Structural Database (CSD)12 contains only the unit cell dimensions of IR (Refcode: ZZZMGS) reported by Wood et al.10 Surprisingly, there is no reference to the unit cell dimensions of IIO, determined in the same study as well as by Egiazaryan et al.,6 nor to the work of Yasui et al., who in 1996 provided a rather extensive report on the crystal structures of both forms.8 For many years, we have been using PT in training courses on hot stage microscopy and polymorphism as an example demonstrating the melting behavior of mixtures of polymorphic forms. It was therefore considered necessary to gain a better understanding of the solid-state properties of this compound which has been known for 70 years. We have chosen to perform a polymorphism screening and to characterize the obtained crystal forms more comprehensively (formation, thermal behavior, thermodynamic and kinetic stability, structural properties) with a variety of analytical techniques such as thermal analysis (hot-stage microscopy, DSC, TGA), vibrational spectroscopy (IR, Raman), X-ray powder diffraction, and single crystal structure analysis. Materials and Methods Materials/Crystallization Experiments. All solvents used for the syntheses of 1-7 were of p.a. quality and purchased from Aldrich.

10.1021/cg8000224 CCC: $40.75  2008 American Chemical Society Published on Web 05/16/2008

1978 Crystal Growth & Design, Vol. 8, No. 6, 2008 Several grams of picryltoluidine (red and orange form, 8 years old) were available from the substance storage of the institute. The crystal forms 1-7 were prepared by dissolving equimolar amounts of the starting materials in a corresponding solvent. All crystallization experiments were carried out under nearly identical conditions. Vials containing solutions of the compound were covered with parafilm and allowed to slowly crystallize and/or evaporate under ambient conditions in a fume hood. Approximately 50 crystallization and evaporation experiments were performed with PT and a variety of solvents: MeOH, EtOH, dichloromethane, chloroform, acetonitrile, acetone, dioxane, cyclohexane, EtOAc, i-PrOH, n-BuOH, THF, DMSO, butan-2-one, pyridine, benzene, toluene, xylene, chlorobenzene, mesitylene, 1,1,1trifluorotoluene, and mixed solvent combinations such as acetone-H2O and MeOH-H2O. Thermal Analysis. Hot-Stage Microscopy (HTM). Thermomicroscopic investigations were carried out using a Reichert Thermovar polarization microscope equipped with a Kofler hot stage (Reichert, Vienna, Austria), linked with a digital camera (Olympus DP50, Olympus Optical Co. Ltd., Vienna, Austria). A Kofler hot bench (Reichert, Vienna, Austria) was employed for the preparation of melt film samples (by fusing the substance between a glass slide and a coverslip). Differential Scanning Calorimetry (DSC). DSC thermograms were recorded with a DSC 7 (Perkin-Elmer, Norwalk, Ct., USA) using the Pyris 2.0 software. Approximately 1-1.5 ( 0.0005 mg of sample (using a UM3 ultramicrobalance, Mettler, Greifensee, Switzerland) were weighed into Al-Pans (25 µL). Dry nitrogen was used as the purge gas (purge: 20 mL · min-1). The instrument was calibrated for temperature with pure benzophenone (mp 48.0 °C) and caffeine (mp 236.2 °C), and the energy calibration was performed with pure indium (purity 99.999%, mp 156.6 °C, heat of fusion 28.45 J · g-1). Heating rates of 5 K · min-1 were used for all investigations. Thermal Gravimetric Analysis (TGA). TGA was carried out with a TGA7 system (Perkin-Elmer, Norwalk, CT, USA) using the Pyris 2.0 Software. Approximately 1 mg of sample was weighed into a platinum pan. Two-point calibration of the temperature was performed with ferromagnetic materials (Alumel and Ni, Curie-point standards, Perkin-Elmer). Heating rates of 5 K · min-1 were applied and dry nitrogen was used as a purge gas (sample purge: 20 mL · min-1, balance purge: 40 mL · min-1). Vibrational Spectroscopy. Fourier Transform Infrared (FT-IR) Spectroscopy. FTIR spectra were recorded with a Bruker IFS 25 spectrometer (Bruker Analytische Messtechnik GmbH, Ettlingen, Germany). The samples were prepared on ZnSe disks and the spectra were recorded in transmission mode with a Bruker IR microscope I (Bruker Analytische Messtechnik GmbH, Ettlingen, Germany), with a 15×-Cassegrain-objective. Spectra were recorded in the spectral range between 4000 and 600 cm-1 at a resolution of 4 cm-1 (64 interferograms per spectrum). Fourier Transform Raman (FT-Raman) Spectroscopy. FT-Raman spectra were recorded with a Bruker RFS 100 Raman spectrometer (Bruker Analytische Messtechnik GmbH, Ettlingen, Germany), equipped with a Nd:YAG laser (1064 nm) as the excitation source and a liquidnitrogen-cooled, high sensitivity Ge-detector. The spectra were recorded in aluminum sample holders using a laser power of 100 mW (64 scans per spectrum) and a resolution of 4 cm-1. Powder X-ray Diffractometry (PXRD). The X-ray diffraction patterns were obtained with a Siemens D-5000 diffractometer (Siemens AG, Karlsruhe, Germany) equipped with a theta/theta goniometer, a Cu KR radiation source, a Göbel mirror (Bruker AXS, Karlsruhe, Germany), a 0.15° Soller slit collimator and a scintillation counter. The patterns were recorded using a tube voltage of 40 kV and a tube current of 35 mA with a scan rate of 0.005° 2θ/s in the 2θ range between 2° and 40°. The solvates were measured in a paste (in mother liquor) and covered with “Mylar-foil” to prevent desolvation. The application of this technique resulted in a preferred orientation of the needles. Single-Crystal X-ray Diffractometry (SCXRD). The X-ray data for 1-7 (see Table 1) were collected on a STOE IPDS-II diffractometer using Mo KR radiation. The crystals were soaked in perfluoropolyether oil, mounted in a litho-loop, and flash cooled. Data collections were performed at -100 °C. The program package WinGX13 (SIR9714 and SHELXL9715) was used for structure solution and refinement. All the H atoms bonded to carbon atoms were generated by a riding model in idealized geometries and refined with Uiso(H) ) 1.2Ueq(C) for phenyl C-H and Uiso(H) ) 1.5Ueq(C) for –CH3 groups. The amino H atoms

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Figure 2. Preparation and phase transformations of PT polymorphs and solvates. in structures 4, 5, 7, and one in 6 (H7) were identified from difference maps. Their positions were refined using the SHELXL97 DFIX 0.88 (0.01) command and their Uiso parameters were refined freely. The hydrogen atoms in the NH groups of 1, 2, 3, and 6 (H21) were located from difference Fourier maps and refined without any constraints. The pyridine molecule in 3 is disordered over two positions with equal occupancies. The chlorobenzene and xylene molecules in 6 and 7, respectively, are both disordered over three positions. The fractional occupancies of the disorder components where refined as 0.51:0.38: 0.11 (6) and 0.29:0.34:0.37 (7).

Results and Discussion Preparation of the Crystal Forms. Slow evaporation/ crystallization from acetone, acetonitrile, EtOAc, MeOH, iPrOH, n-BuOH, MeOH-H2O yields the anhydrous form IR (1), while acetone-H2O, chloroform, and mesitylene resulted in the anhydrous form IIO (2). Solvated crystals were only obtained from pyridine (3), benzene (4), toluene (5), chlorobenzene (6), and xylene (7) solutions. The solvates are highly unstable and revert readily to the unsolvated material. This change is apparent when the crystals turn opaque after removal from their mother liquor. All other solvents result in mixtures of the unsolvated forms IR and IIO. Figure 2 shows a flowchart illustrating the different crystalline forms and their isolation. Figure 3 shows photographs of the differently colored crystal forms (powder and single crystals) of PT obtained in this study. Form IR exhibits a red color, and form IIO is light orange. All five solvates 3-7 have the same color, orange-red. Thermal Analysis. Polymorphs IR and IIO. Figure 4 shows the DSC curves for the PT polymorphs. Form IR (obtained from MeOH) exhibits an endothermic melting peak with an onset of 166.1 ( 0.3 °C and an enthalpy of fusion of 31.3 ( 0.2 kJ · mol-1. The melting peak of form IIO (from acetone-H2O) occurs at 163 ( 0.1 °C with an enthalpy of fusion of 28.6 ( 0.1 kJ · mol-1 (heating rate 5 K · min-1). We can unequivocally conclude from the heat of fusion rule16 that the two forms are monotropically related, and that form IR is the thermodynamically stable form in the entire temperature range (higher melting temperature and higher enthalpy of fusion). The observed melting points were compared with the values reported in the literature (summarized in Table 2). Our experimentally determined order of melting points is consistent with these previous reports, with the exception of those two reports stating that both forms melt at the same temperature.5,19 The melting points in the literature are in a range of 163–164 °C (165.5 °C) and 164–171 °C for form IIO and IR, respectively. Egiazarian et al.6 and Matevosyan et al.7 described

N-Picryl-p-toluidine Polymorphs and Solvates

Crystal Growth & Design, Vol. 8, No. 6, 2008 1979

Figure 3. Photographs of the different colored crystalline forms of PT. Dark red - form IR; light orange - form IIO; orange-red - solvates 3-7.

Figure 4. DSC curves of PT forms IR and IIO (heating rate 5 K · min-1).

a third polymorph (“yellow form”) with a melting point of 161 °C, which, however, could not be reproduced in this study. The melting point for form IIO matches the literature data very well, whereas a distinctly higher value (171 °C6,7) was previously reported for the “red form”. However, it is clear from the associated lattice parameters given in these publications that this “red form” is indeed identical with our form IR. Polymorphs IR and IIO were further examined by hot stage microscopy. The equilibrium melting points of the two polymorphs lie at 163 (IIO) and 166 °C (IR), respectively. Both

modifications show sublimation, starting at 120 °C. Interestingly, the sublimed crystals correspond to the investigated polymorph, that is, red sublimes to red and orange to orange. A transformation from orange to red on heating was only observed in cases where seed crystals of IR were present. Therefore, a mixture, form IIO seeded with form IR crystals, was prepared to investigate the transition. It was observed that the IR crystals grow in the melt droplets of IIO at 163 °C. The color of a supercooled melt and the glass of PT is reddish, indicating that the molecules in IR and the melt adopt similar electronic environments and conformations. Crystallization of the modifications can only be induced by annealing the glass at elevated temperatures, whereas the highest nucleation rate was observed around 130 °C in sandwich preparations between glass slide and coverslip. In contrast to the nucleation rate, the growth rate of both modifications is rather high once nuclei are present. It was found in these experiments that crystallization of the orange form was more likely, albeit not exclusive. To further investigate the thermal behavior of the pure forms and their mixtures, a series of melt film preparations was produced. Figure 5a-h shows photomicrographs of such preparations with both polymorphs (temperature range: 155–166.5 °C). The crystals of the higher melting polymorph IR grow slowly below the melting point of IIO (solid–solid transformation of form IIO to IR). This indicates that form IR

Table 1. Crystallographic Data for the PT Polymorphs and Solvates 1-7 form IR, 1

form IIO, 2

pyridine, 3

benzene, 4

toluene, 5

Cl-Ph, 6

xylene, 7

chemical formula

C13H10N4O6

C13H10N4O6

formula weight crystal system space group T (K) a (Å) b (Å) c (Å) β (°) V (Å3) Z Dcalc (Mg/m) reflns collected unique reflns observed reflns R1 [I > 2σ(I)] wR2 (all) goodness-of-fit

318.25 monoclinic P21/a 173(2) 6.060(9) 17.465(3) 13.132(2) 102.0710(12) 1359.2(4) 4 1.555 7613 2284 1542 0.063 0.121 1.07

318.25 monoclinic P21/c 173(2) 15.251(2) 5.9471(6) 16.288(2) 114.830(10) 1340.7(3) 4 1.577 9727 2858 2195 0.044 0.096 1.06

(C13H10O6N4) · (C5H5N) 397.35 monoclinic P21/a 173(2) 5.8839(9) 23.936(3) 12.9943 (17) 100.6320(11) 1798.7(4) 4 1.467 8883 3679 2315 0.063 0.137 1.00

2(C13H10N4O6) · (C6H6) 714.61 monoclinic C2 173(2) 20.536(3) 6.4018(7) 25.374(4) 101.845(12) 3264.8(8) 4 1.454 7654 3697 2717 0.047 0.105 1.05

2(C13H10N4O6) · (C7H8) 728.63 monoclinic C2 173(2) 20.509(3) 6.4457(8) 25.471(4) 101.534(13) 3299.0(9) 4 1.467 9170 3715 1952 0.067 0.107 1.00

2(C8H10N4O2) · (C6H5Cl) 749.05 monoclinic C2 173(2) 20.514(2) 6.4712(5) 25.315(3) 101.819(10) 3289.3(6) 4 1.513 12572 3698 2802 0.047 0.096 1.07

2(C8H10NO2) · (C4H2O4) 742.66 monoclinic C2 173(2) 20.536(3) 6.4758(7) 26.014(4) 101.487(10) 3390.2(8) 4 1.455 10487 3820 2234 0.070 0.123 0.99

1980 Crystal Growth & Design, Vol. 8, No. 6, 2008

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Figure 5. Photomicrographs of PT modifications: (a) 155 °C, form IR (left) and form IIO (right, major part); (b) 162 °C, form IR is growing and transforms to form IIO; (c) 162 °C; (d) 162.5 °C; (e) 163 °C, melting point of form IIO; (f) 164 °C, form IR grows in the melt; (g) 165 °C, form IR starts to melt; (h) 166.5 °C, melt of PT.

Figure 6. Photomicrographs of the toluene solvate of PT: (a) 25 °C, after their removal from the mother liquor; (b) 35 °C, desolvation starts at the edges of the crystals; (c) 45 °C; (d) 55 °C; (e) 65 °C; (f) 80 °C, completely desolvated, form IIO; (g) 162.5 °C, form IIO starts to melt; (h) 163 °C, residual crystals of form IIO in the melt of PT.

is the more stable polymorph in this temperature range. The residual orange crystals then melt at 163 °C, and at 164 °C the crystals of form IR grow further before they reach their melting point at 166 °C. Our observations show that by heating a melt film preparation of the pure form IIO, neither a solid–solid transition nor an inhomogeneous melting process to IR is ever induced. Thus, we conclude that the presence of seeds of IR is a prerequisite for any transition from IIO to IR on heating as described in the literature.5,8 TGA studies on samples of both polymorphs of PT carried out in the temperature range of 25–170 °C showed neither desolvation nor decomposition. Solvates 3–7. Crystals of all five solvates are unstable at temperatures above 8 °C and desolvate readily immediately after their removal from the mother liquor. The solvates stored at -15 °C, were stable for at least a couple of weeks. Figure 6a-h shows the desolvation process of the toluene solvate in the temperature range from 25 to 165 °C. This behavior is representative for all PT solvates. The desolvation starts at the surface of the crystals and proceeds toward the center, indicated by the blackening of the crystals due to the formation of small crystallites of the anhydrous phase (pseudomorphosis). The PT/solvent ratios were determined by TGA experiments (Figure 7). The solvates 4-7 (benzene, toluene, chlorobenzene, and xylene) exhibit clearly a 2:1 ratio, whereas the pyridine solvate 3 is a monosolvate. The latter has also the lowest thermal stability, and the toluene solvate 5 has the highest. However, the desolvation occurs in all solvates below 80 °C, which

Figure 7. TGA curves of PT solvates 3–7.

indicates low stability. In contrast to the isomorphic solvates 4-7 which desolvate to the metastable form IIO, the pyridine solvate 3 transforms to the higher melting form IR. Form IIO produced by desolvation exists as a fine yellow powder. However, we were unable to produce a “yellow form” with a structure distinct from that of the orange form IIO and suspect that previous reports on a putative yellow form of PT are in fact due to this physical light dispersion effect. A second benzene solvate, reported by Cullinane et al. in 19325 with approximately twice the amount of solvent as the benzene hemisolvate 4, could not be observed in our crystallization experiments either. We doubt that there is a second



Figure 9. FT-IR spectra of PT form IR and IIO and solvates 3-7.

Figure 8. Semischematic energy/temperature diagram of the PT polymorphs. G: Gibbs free energy, H: enthalpy, ∆fusH: enthalpy of fusion, liq: liquid phase (melt). The bold vertical arrows sign the experimentally measured enthalpies.

benzene solvate, since the only indication given for its existence was a reported loss of mass. Furthermore, the production procedure which states that the monosolvate crystallizes from a boiling benzene solution of the dissolved orange-yellow form and the hemisolvate from a solution of the red form is suspicious. We rather assume that the higher benzene solvate derives from a not well dried crystallization product. Likewise, we found no evidence for the existence of a “watercluster” compound, which was suggested by Ilyinia et al.9 These authors used acetone-H2O for the crystallization of this “yellow form”. However, both the fluorescence spectra and the IR data indicate that this “yellow form” is identical with the orange form, which suggests that the “water-cluster” compound represents form IIO, consisting of smaller crystallites. This conclusion can be derived from our crystallization and evaporation experiments, which resulted in a yellow colored form IIO. Thermodynamic and Kinetic Stability. The thermodynamic relationship of the PT polymorphs is displayed in the semischematic energy/temperature diagram16 in Figure 8. Form IR has a higher enthalpy of fusion than form IIO. Therefore, the two polymorphs are monotropically related and the higher melting form (IR) is the thermodynamically stable within the entire temperature range. A sample of form IIO, kept in a glass vessel under ambient conditions, did not transform to the stable form IR within eight years, indicating that the kinetic stability of form IIO is very high. The calculated densities of the two polymorphs are IR: 1.56 g · m-3 and IIO: 1.58 g-3. Thus, the density rule16 is not obeyed, which may be attributed to the higher overall contribution from hydrogen-bonding in form IR as discussed below. Cullinane’s observation that the orange-yellow crystals turn red on heating as a result of a phase transition5 cannot be confirmed. This monotropic phase transition (IIO to IR) never occurred in the pure orange form, and it is obvious that the presence of seeds of form IR is required for this reaction. Also the observation that form IR nucleates from the melt on cooling,

as reported by Yasui et al.8 (Figure 3), is ambiguous. In microscopic preparations nucleation from the melt on slow cooling was never observed and also even after three months’ storage of the melt at ambient conditions no crystallization to one of the forms was observed. Moreover, it should be stressed that the inhomogeneous melting of the orange to the red form occurs only if seeds of the red form are present in the sample. In the absence of such seeds the orange form melts homogeneously. Our result regarding the monotropic relationship of the two modifications is also in contradiction to the heat of solutions reported by Matevosyan et al.7 According to this report the orange form shows a slightly higher heat of solution22 than the higher melting red form, which would indicate that the orange form is the thermodynamically stable form at the measured temperature. The stated solution enthalpy difference between the red and orange forms is about 0.2 kJ · mol-1, which is more than one magnitude smaller than the enthalpy of fusion difference measured by us and definitely within the errors one can derive from dissolution rate curves. However, other authors have also argued that the red form is the thermodynamically more stable form, which can be confirmed by solvent mediated transformation studies.23 Fourier Transform Infrared (FT-IR) and FT-Raman Spectroscopy. The IR spectra (Figure 9) of the two polymorphs are rather distinct from each other. As there is a strong intramolecular hydrogen bond between the secondary amino group and an oxygen atom of the nitro group of the PT molecule, the most striking differences in the spectra appear in the νN-H vibration range. In form IR the band is located at 3323 cm-1, whereas it is shifted to 3257 cm-1 in form IIO. This hypsochromic (blue-shift) shift of ∆νN-H of 66 cm-1 is associated with the different colors of these polymorphs, which are mainly due to charge transfer interactions. This observation is consistent with the difference in intramolecular N-H · · · O bond distances in the single crystal structures of IR (1.98 (4) Å) and IIO (1.88 (2) Å). Other characteristic bands for all the solid-state forms are given in Table 3. The IR spectra of the forms IR and 3 are quite similar except for the νC-H aromatic region. Here, form IR shows a doublet which does not occur for form 3 or any other solid-state form of PT. Similarities between the IR spectra of form sIR and 3 correspond to similarities in their crystal structures (discussed below). The FT-Raman spectra of 1-7 are shown in Figure 10. The most striking differences between the red and orange forms appear in the range of the nitro frequencies, especially the symmetric stretch vibrations of the (C–NO2) groups. The band


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Table 2. PT Melting Points (Ranges) Reported in the Literature melting point (ranges) [°C] author

year

description

Ullmann & Nadai17 Busch & Pungs18 Hantzsch19 James et al.20 Cullinane et al.5 Wood et al.10 Egiazarian et al.6 Matevosyan et al.7 Sekiguchi et al.21 Yasui et al.8

1908 1909 1910 1920 1932 1935 1972 1978 1990 1996

red needles yellow prisms, blood red needles red and orange-yellow crystals blood-red and orange-yellow crystals orange-yellow and red form, two benzene solvates red and orange-yellow form, lattice dimensions red, yellow, orange forms, heat of solutions, lattice dimensions red, yellow, orange, form, heat of solutions, lattice dimensions

a

red

crystal structures of red and orange forms

169 165 164 165 165.5 171 171 165–166.5 167–168

orange

yellow

163 164 163–164 (165.5)a 164 164

161 161

163–164

Transformed on heating.

Figure 10. FT-Raman-spectra of PT form IR and IIO and solvates 3–7.

appears at 1328 cm-1 for form IR and at 1336 cm-1 for form IIO and shows the highest relative intensity. The NO2 symmetric stretch vibration normally occurs near 1350 cm-1 and moves to lower frequencies in the presence of neighboring electron withdrawing groups.24 A stronger hydrogen bond to the nitro group will shift electron density to the amino nitrogen, increases the delocalization of the amino nitrogen lone pair into the ring, increases the double bond character of the C-NO2 bonds, and increases the electron density in the NO2 groups as well as its vibrational frequency.25 For the solvates, the symmetric stretch vibrations of the (C–NO2) groups occur between 1332 and 1336 cm-1. Powder X-ray Diffractometry. The X-ray powder patterns for the polymorphs and solvates are given in Figure 11. Forms IR and IIO can be easily distinguished from one another. Their diffraction patterns differ particularly in the 2θ range between 5° and 15° (peaks for IR: 2θ ) 6.89°, 8.48°, 9.93°, 12.10°; peaks for IIO: 2θ ) 6.34°, 10.83°, 11.31°, 11.72°). The X-ray powder patterns indicate a close structural similarity of the solvates 4-7, and also IR and 3, which is confirmed by the results of the single crystal structure analyses (see below). Single Crystal Structure Analysis. Both polymorphic forms crystallize in the monoclinic space group P21/c with one independent molecule per asymmetric unit. The refinement of IR was carried out in the P21/a setting consistent with the previous reports by Wood et al.10 and Yasui et al.8 The asymmetric unit of the pyridine solvate 3 (P21/a) is composed of one PT and one solvent molecule. The recrystallization of PT from the aromatic solvents benzene, toluene, chlorobenzene, and xylene gave the solvates 4-7 with a PT to solvent ratio of 2:1. Their symmetry is C2 with Z ) 4, and the two independent

Figure 11. X-ray powder diffraction patterns of PT form IR and IIO and solvates 3–7. The patterns of the solvates show a strong preferred orientation due to the flat preparation as a slurry covered by a mylar foil (hump at about 26° 2θ).

Figure 12. Overlay of the PT polymorphs IR and IIO showing the toluidine rings are oriented differently relative to the respective nitrobenzene ring.

PT molecules are conformational opposites. The 2:1 PT/solvate ratio was also determined by TGA. Molecular Geometry. Figure 12 shows an overlay of the PT molecules in the two polymorphic forms. Significant differences occur in the rotation about the two central C-N bonds, and the two toluidine fragments are differently oriented relative to the plane of the respective picryl ring. This change is visible in the torsion angles τ1 and τ2 indicated in Figure 1. The modifications IR and IIO may therefore be regarded as conformational polymorphs. In Table 4, their τ1 and τ2 values are compared with the corresponding parameters computed for the solvates 3-7. The current version of the CSD12 contains another six structures with the N-picryl benzene fragment, and their τ1 and τ2 parameters are listed. Table 4 shows that the typical conformation is characterized by a τ1 value of 20°-24° and a τ2 of 36°-45°. All PT structures in this study, apart from IIO, belong to this category, as well as all the CSD examples



Table 3. Characteristic Infrared Bands for PT Crystal Forms crystal form

ν(NH)

ν(C-H)ar

form IR, 1 form IIO, 2 pyridine, 3 benzene, 4 toluene, 5 Cl-Ph, 6 xylene, 7

3323 3257 3317 3300 3300 3302 3295

3107, 3074 3096 3108 3087 3087 3086 3088

ν(C-NO2) 1358, 1360, 1357, 1359, 1358, 1358, 1356,

1335 1334 1336 1336 1334 1336 1334

except for one (refcode VINCOK29). Thus, the PT geometry of IR may be regarded as a regular and that of IIO as an unusual conformation. This is consistent with an ab initio optimization of either molecular geometry, carried out with an SCF 6-31G(d,p) wave function, giving the lowest energy “gas phase” conformer with τ1 ) 26.26°, τ2 ) 46.79°, quite close to the IR values. However, the energy difference between the two observed conformers is small: ab initio calculations on the molecular structures taken from the polymorphs (but with the bondlengths to hydrogen atoms standardized to neutron values) results in the IIO conformer being less stable than in IR by only 0.29 kJ/ mol at the SCF 6-31G(d,p) level and 1.05 kJ/mol at the MP2 6-31G(d,p) level. A common characteristic of the PT molecules in structures 1-7 is the formation of intramolecular N-H · · · O bonds involving the H atom of the secondary amine and one O atom of a nitro group (Figure 13, Table 5). The different colors of the PT forms are attributed to the variation of the strength (length) of this bond. Analysis of Packing Relationships. The structures 1-7 were compared using the program XPac30 in order to establish recurring packing patterns of PT molecules. This method does not rely on the presence of any specific kind of intermolecular interaction such as hydrogen bonds. The molecular geometry in each structure is parametrized with a set of points, which is then used to generate intermolecular geometric parameters. These are employed to characterize the geometry of supramolecular fragments of each structure. Thus, it is possible to determine whether two given structures have any such fragments in common simply by comparing corresponding sets of parameters. Common structure fragments are also termed supramolecular constructs (SCs) and can be finite or extended (1D, 2D, 3D).30a The XPac method was applied as previously

Figure 13. Intramolecular N-H · · · O H-bond (all forms) and three motifs for intermolecular C-H · · · O(N) interactions in PT forms. Motif I is present in the forms IR, IIO, motif II in all solid forms and motif III in the pyridine solvate (3). For a clearer visualization only one aromatic part of the PT molecule is shown in the three motifs.

described,30a with a set of nine corresponding points comprised of the four nitrogen atoms and the positions labeled C3, C6, C8, C11, and C14 in Figure 1. Thus, the influence of any conformational variation in the PT molecule on the spatial arrangement of the chosen points should be minor. The results described below were obtained using routine medium cutoff parameters (δang ) 10°, δtor and δdhd ) 20°) consistent with a high degree of geometric similarity. The benzene, toluene, chlorobenzene, and xylene solvates 4-7 were confirmed to be isostructural. Thus, four different 3D packing arrangements of PT molecules are present in this study: 1 (IR), 2 (IIO), 3 (the pyridine solvate), and 4–7. However, these four types are structurally closely related to one another. Their relationships are visualized in Figures 14 and 15 and discussed below. All structures contain the same 1D chain A composed of PT molecules (Figure 14a). Neighboring molecules in such a chain are related by translation symmetry and the chain propagates parallel to the a-axis in 1 and 3 and parallel to the b-axis in 2 and 4-7. For 1–3, the length of the translation vector is close to 6.0 Å. The corresponding value is increased by approximately 0.5 Å in the 2:1 solvates 4-7 where the two independent PT molecules (labeled X and Y in Figure 15) also form two separate A stacks. The SC B (Figure 14a) is an arrangement of two A chains around a 21 screw axis. This double chain B is observed in form IIO and in the isostructural solvates 4-7. Another double chain composed of two A units is the SC C (Figure 14a). This centrosymmetric fragment is found in form IIO and in the pyridine solvate 3. However, there is little contact between the two constituent A units of C, so that we regard this latter motif as less significant than the other SCs discussed here. The 2D sheet D in Figure 14a occurs in IR and the pyridine solvate 3. It is composed of A chains whose arrangement generated by glide (generating a set of double chains) and translation symmetry along the respective c-axis. The D sheets of PT molecules lie in the ac-planes of 1 and 3. The observed close similarity between form IR and the pyridine solvate with respect to their a, c, and β unit cell parameters (see Table 1) is therefore not accidental, but a direct consequence of a close packing similarity along these crystallographic directions. The diagram in Figure 14b gives an overview of all identified packing relationships. Each of the four distinct 3D packing modes of PT (1, 2, 3, 4-7) and the four SCs (A-D) is represented as a node and a similarity relationship between two such objects (nodes) by an upward connection between them. Thus, the aggregation of PT molecules is clearly dominated by the A chain. On a higher level, there are two distinct and mutually exclusive aggregation modes for multiple A chains. The double chain B is present in form IIO (2) and all 2:1 solvates (4-7), while the sheet D is found in form IR (1) and the pyridine solvate (3). Starting with PT molecules and using Kitaigorodski’s Aufbau principle,31 these crystal structures can be formally generated in three steps starting with the 1D chain A, the subsequent arrangement of A chains either in double chains B (2, 4-7) or in 2D sheets D (1, 3). Finally, further aggregation of multiple D and B units produces the polymorph structures IR and IIO, respectively, while their combined aggregation with solvate molecules results in 4-7 and 3, respectively. Thus, form IR is effectively a stack of D sheets. These sheets lie perpendicular to the b-axis and their stacking generates both centers of inversion and 21 axes. Figure 15 shows that the conditions are very similar in the pyridine solvate 3. However, neighboring D layers are here separated by a layer of pyridine


Braun et al.

Table 4. Torsion Angles, τ1 and τ2, which Show the Flip of the Toluidine Ring in Different Crystal Forms of PT, 1-7a crystal form form IR, 1 form IIO, 2 pyridine, 3 benzene, 4 toluene, 5 Cl-Ph, 6 xylene, 7 a

τ1 (°) C4-C3-N7-C8 23.80 -12.52 23.03 -22.52 23.41 20.61 -23.33 21.95 -22.13 -22.54 20.59

τ2 (°) C13-C8-N7-C3 43.07 -54.35 44.85 -37.74 40.13 37.57 -40.86 37.40 -41.07 -36.68 42.72

CSD REFCODE

τ1 (°)

τ2 (°)

30.29

-43.91

-29.58

-43.16

25.85

42.69

TNDPAM

28.60

-31.15

VINCOK29

16.96

51.01

29

-29.98

38.89

26

INUPIQ

27

TAFCAE

TAFCEI27 28

VINDAX

Values compared with the corresponding parameters computed for another six structures from the CSD with a N-picryl benzene fragment.

Figure 14. Results of the XPac investigation of packing relationships. (a) Supramolecular constructs A-C (1D) and D (2D) composed of PT molecules, all viewed along the translation vector of A. 1D constructs appear as one or two molecules (single or double chains) and the 2D construct D as a row of molecules. (b) Scheme showing the packing relationships between the polymorphic forms IR (1) and IIO (2), the pyridine solvate (3) and 2:1 solvates (4-7). A-D are the supramolecular constructs of (a). Upward connections indicate subset-superset relationships; for example, the SC A is present in all structures and all other SCs. For information on the generation of this kind of diagram see ref 30b.

Figure 15. Packing of PT (magenta) and solvate molecules (green, 3 and 4-7 only). All structures are viewed along the translation vector of A (1, 3: [100]; 2, 4-7: [010]). Examples of the essential SCs A, B, and D from Figure 14a are marked.

molecules. The solvent molecules are located in channels parallel to the a-axis. The observation that the desolvation of the pyridine solvate leads to form IR is highly significant in this respect. The desolvation mechanism could start with the removal of the

solvate through the [100] channels. This would leave the D sheets intact to a large extent. The space vacated by solvent molecules would be filled due to a subsequent mutual readjustment of neighboring D units, resulting in an effective relative



Table 5. Geometrical Parameters for the Intramolecular N-H · · · O Hydrogen Bond in PT Polymorphs and Solvates 1-7 modification/ solvate form IR, 1 form IIO, 2 pyridine, 3 benzene, 4 toluene, 5 Cl-Ph, 6 xylene, 7

interaction N(7)-H · · · O(2) N(7)-H · · · O(2) N(7)-H · · · O(2) N(7)-H · · · O(2) N(21)-H · · · O(8) N(7)-H · · · O(2) N(21)-H · · · O(8) N(7)-H · · · O(2) N(21)-H · · · O(8) N(7)-H · · · O(2) N(21)-H · · · O(8)

(N-H) d (H · · · A) D (D · · · A) Å Å Å 0.87(4) 0.89(2) 0.88(3) 0.88(1) 0.88(1) 0.88(1) 0.88(1) 0.88(1) 0.87(5) 0.88(1) 0.88(1)

1.98(4) 1.88(2) 1.90(3) 1.93(4) 1.90(3) 1.96(7) 1.88(5) 1.93(3) 1.91(1) 1.92(4) 1.93(5)

2.632(4) 2.611(2) 2.632(3) 2.614(4) 2.601(5) 2.601(7) 2.600(8) 2.609(4) 2.604(4) 2.609(6) 2.607(8)

θ° 131(3) 139(2) 138(2) 133(4) 135(4) 128(7) 137(6) 132(3) 136(4) 134(5) 133(6)

shift of one D unit against another by approximately a quarter of a translation along the c-axis. In the structure of IIO, the B-type fragments with their intrinsic 21 symmetry form 2D stacks that lie in ab-planes. Further aggregation of these stacks to a 3D structure generates glide planes and centers of inversion. By contrast, the independent PT molecules X and Y of the 2:1 solvates 4-7 form two separate B chains. The B units of X are stacked on top of one another to give 2D stacks that lie in ab-planes. This is reminiscent of IIO, but neighboring B units in such 2D fragments are related by 2-fold rotation rather than a 21 operation. The Y molecules and solvent molecules are arranged together in 2D double sheets which exhibit 2-fold symmetry and lie in abplanes. The ubiquitous structural fragment A shows a remarkable resilience. An effort was made to gain a better understanding of the forces that drive the aggregation of PT molecules in this particular fashion by analyzing the intermolecular interactions within this motif. However, the most noticeable shorter contacts display either intrinsically unfavorable geometries, for example NH · · · O(nitro) with 2.823 Å, 96.2° in IIO, or they are associated with geometries that are not stable through the series. For example, the shortest (benzyl)CH · · · O(nitro) distance in the A unit of IIO, 2.676 Å, 163.0°. The same contact is elongated to X: 3.313 Å, 165.0° and Y: 3.094, 154.3° in the toluidine solvate 5. In conclusion, individual specific intermolecular contacts do not explain the preferred aggregation of PT molecules in A stacks, which appears instead to be driven mainly by space filling effectiveness combined with a lack of suitable and similarly favorable alternatives. Intermolecular Interactions. It follows from the molecular structure of PT that the contacts between van der Waals surfaces of neighboring PT in 1-7 will be determined to a large extent by contacts between nitro O atoms and H atoms of the picryl and toluidine moieties. The only strong hydrogen bond donor of PT, the secondary amino group, is exclusively involved in intramolecular hydrogen bonding. In this section, the specific intermolecular contacts in 1-7 are investigated and their relation to the supramolecular constructs (identified above) are discussed. A list with C-H · · · O and C-H · · · π contact parameters is available as Supporting Information. The two polymorphs of PT represent an exception to the density rule, since form IIO, the less stable form at absolute zero temperature, is denser than the stable form IR. Significant intermolecular C-H · · · O contacts can be identified in both structures, and dH · · · O-θ and DC · · · O-θ scatter plots for C-H · · · O are given in Figure 16. Form IR has six contacts within the range up to the sum of the van der Waals radii, while polymorph IIO has just three. Furthermore, by far the most favorable contact geometry (d 2.30 Å, 170°, C-H

Figure 16. (a) d-θ and (b) D-θ scatter plot for C-H · · · O interactions in crystal structures IR (circles) and IIO (triangles). The C-H distances were normalized to 1.083 Å using the program PLATON v.1.12.32 The sum of the van der Waals radii was used as cutoff parameter.

Figure 17. Left panel: 2D fingerprint plots for the PT polymorphs IR (a) and IIO (c). Right panel: portion of the fingerprint plots for IR (b) and IIO (d) showing exclusively O · · · H and H · · · O contacts. de and di are the distances to the nearest atom centers exterior and interior to the surface. All N-H and C-H distances were automatically neutron normalized to 1.009 and 1.083 Å.

vectors normalized to 1.083 Å), associated with an inversion related dimer (Figure 13, motif I), is observed in IR and has no counterpart in IIO. The atom-atom contacts in the two PT polymorphs were also investigated via visualization of their respective Hirshfeld surfaces.33 The resulting two-dimensional fingerprint plots (di vs de, where di is the distance to the nearest atom center


Braun et al.

Figure 18. Fragments of the crystal structure of the form IR. (a) Ladder structure based on C-H · · · O contacts combining motifs I and II (Figure 13). (b) Zig-zig arrangement of ladders to give a corrugated sheet. For details of the geometric parameters of the C-H · · · O interactions please see Supporting Information.

Figure 19. Fragments of the crystal structure of the form IIR. Chain structure based on C-H · · · O contacts combining motifs I and II (Figure 13). For details of the geometric parameters of the C-H · · · O interactions please see Supporting Information.

Figure 20. Fragment of the crystal structure of the pyridine solvate (3) viewed along the a-axis, showing tape composed of two separate chains of PT and pyridine molecules linked by the C-H · · · O and C-H · · · N interactions of motif III (Figure 13).

interior to the surface, and de exterior) show considerable differences (Figure 17). There are fewer voids in the upper region of the plot of form IIO, and these voids are also less scattered than those that appear in the IR plot. This indicates a more efficient packing of PT molecules in IIO, consistent with the difference in calculated densities (IIO is denser). The O · · · H and H · · · O contacts comprise approximately 40% of the total Hirshfeld surface in both cases (42.3% for IR and 39.8% for IIO). The differences between IR and IIO are highlighted in the right panel of Figure 17. These diagrams represent exclusively intermolecular O · · · H and H · · · O contacts. The plots for both forms exhibit spikes (IR: labeled 1a for the acceptor and 1b for the donor, IIO: labeled 3a/3b) representing the C-H · · · O interactions. However, the spikes of form IR associated with the relatively short interactions of motif I (Figure 13) are much sharper. In contrast, the geometry of the shortest C-H · · · O contact in IIO is less favorable (2.50 Å, 133°). Furthermore, the upper left plot for IR in Figure 17 displays wings which are due to C-H · · · π

contacts in the region of de ) 1.1 Å – di ) 1.7 Å and de ) 1.7 Å – di ) 1.1 Å and labeled 2a and 2b in Figure 17. These interactions also have no equivalent in IIO. The centrosymmetric dimeric C-H · · · O motif I (Figure 13) involves one nitro O atom and one H atom of the picryl moiety of each molecule). These dimers, related by a translation along c are further linked by two C-H · · · O contacts depicted as motif II in Figure 13 into the ladder structure of Figure 18a. The diagram in Figure 18b shows how such ladders are arranged in a zigzag fashion along the b-axis, to give a corrugated sheet. This aggregation along b is mediated by the weak C-H · · · π contacts that are visible in the Hirshfeld plot of IR. Figure 19 shows that form IIO also contains a 1D structure which combines motif I and II type C-H · · · O interactions. However, the geometry of these chains propagating along the a-axis is entirely different from the ladder in IR (Figure 18a). Lattice energy calculations for the two polymorphs indicate that the two polymorphs are quite close in energy. Using rigidmolecule lattice energy minimizations with a DMA (MP2 6–31G(d,p)) electrostatic model and one set of empirical repulsion-dispersion potentials34 gives the intermolecular lattice energy as -133.0 kJ/mol for IR and -131.9 kJ/mol for IIO (though this stability difference will become slightly larger if the conformational energy is taken into account). More extensive DMAflex calculations,35 in which the molecular geometry is ab initio optimized, with the values of τ1, τ2, the methyl and nitro torsions being optimized to balance the intramolecular SCF 6-31G(d,p) conformational energy with the intermolecular lattice energy (calculated with an alternative model potential (FIT36) and PBEPBE 6-31G(d,p) DMA electrostatic model), gives the lattice energy of IR as -135.4 kJ/mol and IIO as -134.6.kJ/ mol. The reasonable agreement of these two different methods of estimating the lattice energy confirms that IR is only slightly more stable than IIO. The most significant intermolecular interactions in the pyridine solvate 3, motif III in Figure 13, involve the pyridine molecule and the picryl moiety of PT. Furthermore, the picryl unit has an additional C-H · · · O motif II contact to the toluidine ring of a neighboring PT molecule. The 1D tape structure of Figure 20 is obtained where the coplanar pyridine and picryl rings lie in bc-planes. The pyridine/PT interaction of motif III



Figure 21. Fragments of the isostructural benzene (a), toluene (b), chlorobenzene (c), and xylene (d) solvate structures 4–7 showing PT (X: green, Y: red) and solvate molecules (blue). Intramolecular N-H · · · O hydrogen bonds and weak C-H · · · O interactions are drawn as dashed lines (cutoff parameter: sum of the van der Waals radii).

is reminiscent of the PT/PT interaction of motif I (Figure 13) and would indeed be replaced by the latter in the desolvation mechanism suggested in the previous section. Furthermore, the motif II contacts along the b-axis in both form IR and 3 describe the linkage of two SC A units, identified in our packing comparison, into 2D sheets of type D. Another weak interaction of the pyridine with the picryl moiety of PT is formed through π · · · π contacts. Figure 21 shows fragments of the isostructural solvates 4–7. As mentioned above, the independent PT molecules X and Y form separate B double chains with 21 symmetry. As in IIO, the linkage between the two A units of B employs motif II C-H · · · O contacts (Figures 13, 19). Adjacent B fragments of molecule X are linked along the a-axis via additional C-H · · · O contacts. Each B unit formed by the second conformer Y bridges between these chains via C-H · · · O contacts, so that open corrugated sheets of linked PT molecules are generated which lie in ac planes and allow for the inclusion of molecules of the respective solvent. The thermal stability of the solvates 4-7 may be low because solvent and PT molecules interact mainly through weak π · · · π, C-H · · · O, and C-H · · · π interactions. The C-H · · · O motif II (Figure 13) was identified in all four distinct 3D packing arrangements studied (1, 2, 3, 4–7). Motif

I occurs in two structures (1, 2), while the alternative motif III is restricted to the pyridine solvate 3. A search of the CSD (version 1.8, Nov.ember 200512) revealed 596, 132, and 7 previous observations of motifs I, II, and III, respectively. This suggests that the occurrence of motifs I and II is predictable to some extent for compounds similar to PT. Conclusions PTrepresents a very interesting example of conformational color polymorphism, showing at least two polymorphs and five solvates. The 2:1 solvates 4-7 are isostructural and their structures are distinct from that of the 1:1 pyridine solvate 3. The solvent molecules are either located in channels (4-7) or in layers (3) from where they can escape easily. The PT/ solvent ratio was confirmed with TGA experiments. 3 desolvates to the higher melting form IR (Tfus: 166.1 °C ( 0.3, ∆fusH: 31.3 kJ mol-1 ( 0.2), whereas 4-7 desolvate to the metastable form IIO (Tfus: 163.5 °C ( 0.1, ∆fusH: 28.6 kJ mol-1 ( 0.1). From the heat of fusion rule16 it is obvious that the two forms are monotropically related. However, the calculated densities of the two polymorphs do not follow the density rule. This could possibly be due to the overall hydrogen-bond contribution which is higher in form IR.


Because of the presence of strong intramolecular N-H · · · O hydrogen bonds, the IR spectra of the polymorphs show clear differences. A short N-H · · · O hydrogen bond in form IIO (νN-H: 3257 cm-1) results in a hypsochromic (blueshift) shift of the νN-H band of 66 cm-1 with respect to form IR (3323 cm-1). This correlates with the color change in these modifications due to differences in the charge transfer interactions. Our analysis using the XPac approach reveals a supramolecular 1D chain (A) of PT molecules as the common feature of all seven crystal structures. However, molecules forming this recurring pattern are not linked by any prominent intermolecular interaction that would potentially explain its persistence in different crystal structure environments. Furthermore, the A chain has a remarkable geometrical flexibility, so that its translation vector is elongated by as much as 10% in the solvates 4-7. This observation supports the interpretation of A primarily with space filling arguments. On the next level of aggregation, multiple A chains are combined either in a double chain B (in IIO, 4-7) or in a 2D structure D (in IR, 3). A complementary interpretation of the seven crystals structures in terms of C-H · · · O and other weak intermolecular interactions generates very detailed geometric parameters for each individual structure, but this information cannot shed much light on the essential packing similarities that the seven forms of PT undoubtedly possess. Furthermore, it is known that such interactions do not stabilize the lattice energy significantly. Our investigation confirms neither the existence of a yellow hydrate (“water-cluster” compound) suggested by Ilynia et al.9 nor that of a third, yellow polymorph.6,7 We suspect that both of these previously postulated forms concern in fact the orange form IIO, which shows a yellowish color when produced as microcrystalline powder by desolvation from solvates. The lesson from these findings is that visually observable color differences should not be overrated and that additional analytical proofs are always required to attest any structural difference. Moreover, only one of the two different benzene solvates (mono and hemisolvate), reported by Cullinane et al.,5 as obtained from a benzene solution of the forms IR and IIO, respectively, could be verified. Our experiments always resulted in the hemibenzene solvate 4 independent of the staring material. This work demonstrates the challenges of establishing the range and relationship between possible solid forms of a molecule which polymorphism has long been apparent from its color changes and highlights the benefit of different complementary approaches in order to understand the causes and principles of polymorphism. Acknowledgment. R.K.R.J. acknowledges financial support from a Lise-Meitner grant M862-B10 of the FWF (Austrian Science Fund). D.E.B., V.K., and U.J.G. are grateful for the financial support from SANDOZ GmbH. Supporting Information Available: Demonstration of color differences in distinctly prepared bulk samples, melt film preparations, and crystallized samples in glass vial; photomicrographs of the two PT modifications (film preparation), and sublimed crystals; thermal ellipsoid plots of the PT forms; plot of the disorder modeling of the solvent molecules in 3, 6, and 7; Hirshfeld 2D fingerprint plots for the PT solvates 3-7; additional figures of the crystal structures for IIO (showing the tapes) and 3 (stacking of the layers, overlay of the PT molecules of IR and 3, and a comparison of the unit cells of IR and 3); geometrical parameters for the C-H · · · O and C-H · · · π interactions. This information is available free of charge via the Internet at http:// pubs.acs.org. The crystallographic data of the forms 1–7 have been deposited with the Cambridge Crystallographic Data Centre, CCDC

Braun et al. Nos. 673766 (IR), 673767 (form IIO), 673770 (3), 673768 (4), 673771 (5), 673769 (6), 673772 (7).

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