Article pubs.acs.org/crystal
Isomorphous Crystals by Chloro−Methyl Exchange in Polymorphic Fuchsones Published as part of the Crystal Growth & Design virtual special issue In Honor of Prof. G. R. Desiraju Naba K. Nath and Ashwini Nangia* School of Chemistry, University of Hyderabad, Central University PO, Prof. C. R. Rao Road, Gachibowli, Hyderabad 500 046, India S Supporting Information *
ABSTRACT: The X-ray crystal structures of four fuchsone derivatives in which a chloro group is replaced by methyl were analyzed to understand isostructurality upon Cl−Me exchange in a polymorphic family of molecules. The four methyl groups in tetramethyl fuchsone (TMF, 2,6-dimethyl and α,α-di-ptolyl) were substituted with chlorine pairwise to give dichloro dimethyl (CMF, 2,6-dichloro and α,α-di-p-tolyl), dimethyl dichloro (MCF, 2,6-dimethyl and α,α-di-p-chlorophenyl), and tetrachloro derivatives (TCF, 2,6-dichloro and α,α-di-pchlorophenyl). The first three compounds are polymorphic, whereas TCF afforded one crystal modification only. TMF, CMF, and MCF are isostructural and isomorphous crystals in the category of polymorphs, solid solutions, and solvates. The first case of color polymorphism in fuchsone dyes is reported for CMF dimorphs. The formation of solid solution is one of the most stringent tests of isostructutality, which was observed for TMF, CMF, and MCF but not for TCF. Crystal packing in TCF is dominated by short Cl···Cl interactions, and consequently this crystal structure is different from the first three members which are largely a result of space filling. Crystal structures were analyzed using the XPac program to calculate the dissimilarity index of supramolecular constructs and Hirshfeld fingerprint plots to quantify the contribution of Cl···Cl interactions. Isostructurality was observed up to 50% exchange of Cl with Me, but after that point the structure deviates to another packing motif.
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INTRODUCTION
predictable. Its occurrence frequency was estimated in crystal structures.7b We decided to test the validity of Cl−Me exchange in conformationally flexible molecules which are also polymorphic. The diverse crystal packing motifs in polymorphic fuchsones would mean that it should be possible for such molecules to adopt a slightly different crystalline arrangement by a change in substituent and/or subtle changes in intermolecular interactions. Fuchsones, or α,α-diphenyl-l,4-benzoquinone methides, attracted structural interest because of their historical application as triphenylmethane dyes.8 We revisited polymorphism in fuchsones9 and found that steric factors play a role in chiral crystallization. In continuation of these studies, we now report systematic replacement of Me → Cl (Scheme 1) to obtain four related molecules. Even as chloro−methyl exchange can result in isostructural crystals, the same was expected to be nontrivial in fuchsones for two reasons: (1) fuchsones exist as conformational
Polymorphism (different crystal modifications of the same compound) is well-known and widely studied by academic and industrial researchers because of its importance in diverse applications such as drugs, pharmaceuticals, dyes, pigments, optical devices, etc.1 The opposite phenomena of isostructurality2 (occurrence of the same or similar crystal structure for related molecules) is a historical topic,3 though relatively less studied in recent times.4 Conformationally flexible molecules have a high propensity to give polymorphs because of a greater number of torsion angles accessible under ambient conditions compared to rigid molecules.5 Functional groups which have roughly the same size/volume can give isostructural crystals. Chloro and methyl groups are often viewed as structural equivalents. According to Kitaigorodskii’s principle of close packing,6 chloro (V = 21 Å3) and methyl (V = 19 Å3) groups have a similar size and spherical shape, and hence it is possible that Cl/Me interchanged molecules have the same crystal packing, the so-called chloro− methyl exchange rule.7 However, Cl−Me exchange is not always © 2012 American Chemical Society
Received: July 19, 2012 Revised: September 9, 2012 Published: September 14, 2012 5411
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isomorphous pair. TCF has an entirely different crystal structure. The two solvated crystal structures, CMF-d and CMF-t also form an isomorphous pair. TMF-I, CMF-I, and MCF-I crystallized in monoclinic space group P21/c, and TMF-II and MCF-II crystallized in triclinic space group P1̅ with one molecule in the asymmetric unit. TMF-III, CMF-II, and MCF-III crystallized in monoclinic space group P21/c, P21/c, and C2/c respectively with Z′ = 1, 1, and 0.5. Toluene and dioxane were incorporated in the crystal lattice of CMF (space group P1̅) when crystallization was carried out from these solvents. TCF crystallized in the monoclinic space group P21/n with completely different cell parameters compared to the remaining crystal structures in this series. Crystal Structure Analysis. TMF-I. Reflections were collected on a block-shaped crystal of TMF-I obtained from n-hexane and data were solved and refined in space group P21/c with one molecule in the asymmetric unit. In the crystal structure C−H···O hydrogen bonded (C16−H16···O1, 2.39 Å, 138.3°) molecules form zigzag chains along the c-axis which are connected to another antiparallel chain by another C−H···O hydrogen bond (C9−H9···O1, 2.29 Å, 147.0°) as centrosymmetric dimers (Figure 1). TMF-II. X-ray data collection on block-shaped crystals of TMF-II obtained from benzene were solved and refined in space group P1̅ with Z′ = 1. Bifurcated C−H···O hydrogen bonds (C15−H15···O1, 2.26 Å, 136.3°, C9−H9···O1, 2.23 Å, 170.1°) form centrosymmetric dimers which are stacked along the a-axis. The structure is completed by the close packing of these centrosymmetric dimers (Figure 2). TMF-III. Small needle-like single crystals of poor quality were obtained of TMF-III from methanol. Structure solution and refinement in space group P2 1 /c gave one symmetryindependent molecule in the unit cell. The carbonyl oxygen is involved in trifurcated C−H···O hydrogen bonds, two of which make zigzag chains along the b-axis (C10−H10···O1, 2.25 Å, 158.1°, C22−H22B···O1, 2.55 Å, 151.5°) to form a 2D layer in the ab plane. Two such layers are connected by another C−H···O hydrogen bond (C23−H23C···O1, 2.46 Å, 142.0°) along with auxiliary C−H···π interactions (2.86 Å, 137.0°; 2.62 Å, 151.3°; 2.61 Å, 144.8°) (Figure 3). CMF-I. X-ray reflections on an orange colored block morphology crystal obtained from n-hexane were solved and refined in space group P21/c with one molecule in the asymmetric unit. In the crystal structure, similar to TMF-I, C−H···O hydrogen bonded (C16−H16···O1, 2.40 Å, 140.8°) molecules form chains along the c-axis, which are in turn connected to another antiparallel chain by a further C−H···O hydrogen bond (C9−H9···O1, 2.28 Å, 145.2°) and C−H···Cl interactions (C18−H18···Cl1, 2.80 Å, 169.0°) to form a 2D sheet in the bc plane. A C−H···Cl (C3−H3···Cl2, 2.82 Å, 122.3°) interaction between the sheets completes the 3D packing (Figure 4).
Scheme 1. Fuchsones Selected To Study Chloro−Methyl Exchange Isostructurality In a Polymorphic System
polymorphs9 due to restricted rotation at the α diphenyl methylene moiety; and (2) the presence of multiple C−H donors of comparable acidity for a single acceptor pitches hydrogen bonding competition to give different packing arrangements. And finally, isostructurality and polymorphism are not so common a phenomenon in the same system.4a
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RESULTS AND DISCUSSION The four derivatives of fuchsone studied are tetramethyl fuchsone (TMF), dichlorodimethyl fuchsone (CMF), dimethyldichloro fuchsone (MCF), and tetrachloro fuchsone (TCF) (see structures in Scheme 1). The synthetic protocols to prepare these compounds are given in the Experimental Section. Crystallization and Polymorphism. The four compounds were crystallized from different solvents to obtain novel solidstate forms for X-ray diffraction. TMF crystallized as trimorphs, form I (TMF-I), form II (TMF-II), and form III (TMF-III); CMF gave dimorphs, form I (CMF-I) and form II (CMF-II), along with solvated structures, dioxane (CMF-d) and toluene (CMF-t); and MCF gave trimorphs, form I (MCF-I), form II (MCF-II), and form III (MCF-III). Only one crystal structure was obtained for TCF under similar efforts of polymorph hunting. The crystalline polymorphs were obtained by slow evaporation at ambient temperature in different solvents (conditions are summarized in Table 1). Concomitant crystallization of polymorphs was observed in several cases, but it was possible to manually pick out single crystals for X-ray diffraction. A comparison of unit cell parameters (Table 2), space group, and crystal structure analysis showed that TMF-I, CMF-I, and MCF-I form an isomorphous cluster, and TMF-II and MCF-II are another
Table 1. Solvents Used for the Crystallization of Fuchsone Polymorphs compounds
Form I
TMF
n-hexane, EtOAc, MeOH, CH3NO2, CH3CN, CH2Cl2, mesitylene toluene, dioxane, hexane, benzene, THF, CH3CN, diethyl ether benzene, diethyl ether, MeOH
CMF MCF TCF
Form II n-hexane, benzene, EtOAc, cyclohexane, diethyl ether, mesitylene CH3NO2, mesitylene CH3CN, dioxane, diethyl ether CH2Cl2, CH3NO2
Form III
solvate
MeOH, diethyl ether dioxane, toluene diethyl ether, di-isopropyl ether
n-hexane, benzene, diethyl ether, mesitylene, CH2Cl2 5412
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Table 2. Crystallographic Parameters of Cl/Me Fuchsones and Their Solid Solutions crystal data emp formula formula wt crystal system space group T (K) a (Å) b (Å) c (Å) α (°) β (°) γ (°) Z′/Z volume (Å3) Dcalc (g cm−3) μ (mm−1) reflns collected unique reflns observed reflns R1 [I > 2σ(I)], wR2 GOF CMF-II C21H16Cl2O 355.24 monoclinic P21/c 100 8.1079(5) 17.6794(12) 12.3042(8) 90 107.3880(10) 90 1/4 1683.12(19) 1.402 0.390 17199 3306 3068 0.0292, 0.0786 1.040 MCF-II C21H16Cl2O 355.24 triclinic P1̅ 100 7.5140(7) 8.1314(7) 15.2380(14) 97.0260(10) 101.4830(10) 104.0540(10) 1/2 870.71(14) 1.355 0.377 8918 3344 3001 0.0365, 0.0935 1.039
TMF-I C23H22O 314.41 monoclinic P21/c 100 7.6297(5) 12.5889(8) 18.2064(11) 90 95.4670(10) 90 1/4 1740.76(19) 1.200 0.071 17000 3233 3089 0.0498, 0.1300 1.056 CMF-d
TMF-II
TMF-III
CMF-I
C23H22O 314.41 triclinic P1̅ 100 7.4822(6) 8.1328(6) 15.3014(11) 97.5620(10) 101.0460(10) 102.9920(10) 1/2 875.49(11) 1.193 0.071 9080 3406 3235 0.0430, 0.1107 1.066
C23H22O 314.41 monoclinic P21/c 100 12.869(3) 17.255(4) 7.960(2) 90 99.436(5) 90 1/4 1743.6(7) 1.198 0.071 16414 3085 2472 0.0755, 0.1665 1.113
C21H16Cl2O 355.24 monoclinic P21/c 100 7.5479(5) 12.4908(9) 18.3342(13) 90 95.9850(10) 90 1/4 1719.1(2) 1.373 0.382 17449 3389 3105 0.0324, 0.0823 1.051 MCF-I
CMF-t
C23H16Cl2O2 395.26 triclinic P1̅ 298 7.222(2) 12.034(4) 12.859(4) 102.963(5) 102.420(5) 92.363(5) 1/2 1058.9(6) 1.240 0.320 10898 4157 2518 0.0540, 0.1489 0.979 MCF-III
TCF
C21H16Cl2O 355.24 monoclinic C2/c 100 19.8402(15) 10.8101(8) 7.7823(6) 90 90.00 90 0.5/4 1669.1(2) 1.414 0.393 8341 1630 1562 0.0334, 0.0880 1.071
C19H10Cl4O 396.07 monoclinic P21/n 100 7.402(3) 27.806(11) 8.442(3) 90 104.514(6) 90 1/4 1682.1(11) 1.564 0.706 13223 3310 2749 0.0487, 0.1161 1.054 5413
C24.50H16Cl2O 397.27 triclinic P1̅ 100 7.2779(7) 11.8390(11) 12.4604(11) 101.2630(10) 103.8560(10) 91.1900(10) 1/2 1019.73(16) 1.294 0.330 10683 4000 3422 0.0396, 0.1082 1.048 CMF + MCF
C21H16Cl2O 355.24 monoclinic P21/c 100 7.5638(16) 12.612(3) 18.207(4) 90 96.092(3) 90 1/4 1727.0(6) 1.366 0.380 17374 3369 3208 0.0328, 0.0856 1.059 TMF + CMF
C21H13.25Cl2O 352.47 monoclinic P21/c 100 7.5735(6) 12.5391(11) 18.2526(16) 90 95.7320(10) 90 1/4 1724.7(3) 1.357 0.380 17571 3402 3173 0.0423, 0.1093 1.110
C22H19.25ClO 335.07 monoclinic P21/c 100 7.5966(8) 12.5450(13) 18.2688(18) 90 95.684(2) 90 1/4 1732.4(3) 1.285 0.225 17513 3416 3174 0.0378, 0.0932 1.077
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Table 2. continued TMF + MCF-1
TMF + MCF-2
TMF + MCF-3
TMF + MCF-4
C22H19.25Cl0.75O 326.21 monoclinic P21/c 100 7.6140(5) 12.5924(8) 18.2117(12) 90 95.6060(10) 90 1/4 1737.8(2) 1.247 0.186 17702 3447 3288 0.0392, 0.0999 1.091
C22.50H20.50Cl0.50O 324.61 triclinic P1̅ 100 7.4976(7) 8.1301(7) 15.2759(13) 97.4970(10) 101.2120(10) 103.2220(10) 1/2 874.13(13) 1.233 0.147 8980 3381 3284 0.0450, 0.1110 1.145
C21.50H17.75Cl1.50O 345.28 monoclinic C2/c 100 19.853(3) 10.8323(15) 7.8131(11) 90 90.00 90 0.5/4 1680.3(4) 1.365 0.311 7930 1500 1402 0.0579, 0.1163 1.319
C21.50H17.75Cl1.50O 345.28 monoclinic P21/c 100 7.6040(6) 12.5706(11) 18.1989(15) 90 95.8030(10) 90 1/4 1730.7(2) 1.325 0.302 17520 3422 3214 0.0479, 0.1034 1.208
Figure 2. Molecular packing in TMF-II. (a) Stacks of centrosymmetric dimers formed by C−H···O hydrogen bonds. (b) Close packing of dimer units.
tance of overlapping quinoid rings is 4.65 Å whereas in CMF-II it is 3.99 Å. Therefore the centrosymmetric dimer of CMF molecules is connected to the nearest neighbor via two C−H···Cl interactions in CMF-II (C3−H3···Cl1, 2.81 Å, 148.3° and C10− H10···Cl2, 2.79 Å, 128.1°) compared to one interaction in CMF- I. Differences in the crystal structures of CMF-I and CMF-II are shown in Figure 5. CMF-d and CMF-t. CMF crystallized as dioxane (CMF-d) and toluene (CMF-t) solvates on crystallization from the respective solvents. The solvates are isomorphous, having centrosymmetric dimers of bifurcated C−H···O hydrogen bonds which stack along the a-axis. A cavity accommodates solvent molecules by space filling (Figure 7). MCF-I. Block morphology crystals of MCF-I were obtained from benzene. X-ray diffraction afforded the crystal structure
Figure 1. Molecular packing in TMF-I. (a) Antiparallel chains of C− H···O hydrogen bonded molecules are connected by another C−H···O interaction to form 2D sheets. (b) Close packing of molecules. H atoms are omitted for clarity except for those which participate in C−H···O, C−H···Cl, C−H···π interactions throughout this paper.
CMF-II. Purple colored block morphology crystals of CMF-II obtained from mesitylene gave the X-ray crystal structure in space group P21/c with one molecule in the asymmetric unit. The structure is similar to CMF-I, but there are differences due to the variation in the distance between the quinoid rings of the centrosymmetric dimer. In CMF-I, the centroid-to-centroid dis5414
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Figure 3. Molecular packing in TMF-III. (a) C−H···O hydrogen bond forms 2D layers in the ab-plane (layers are shown with different shading). (b) C−H···π interactions connecting the layers.
Figure 4. CMF-I. (a) Chains of C−H···O hydrogen bonded molecules are connected to another antiparallel chain by C−H···O hydrogen bond and C−H···Cl interactions to form 2D sheets in the bc plane. (b) Such sheets are connected by C−H···Cl interactions.
in monoclinic space group P21/c with one molecule in the asymmetric unit. The crystal structure is isomorphous with that of form I of TMF and CMF, i.e., TMF-I and CMF-I. Zigzag chains of C−H···O hydrogen bonded molecules (C18−H18···O1, 2.35 Å, 139.9°) are connected to an inversionrelated chain by C−H···O (C9−H9···O1, 2.24 Å, 143.9°) and C−H···Cl (C13−H13···Cl2, 2.66 Å, 140.1°) interactions forming a sheet in the bc-plane (Figure 8). MCF-II. Plate morphology crystals obtained from CH2Cl2 were solved and refined in the triclinic space group P1̅ with Z′ = 1. Centrosymmetric dimers formed by bifurcated C−H···O hydrogen bond (C9−H9···O1, 2.20 Å, 173.3° and C19− H19···O1, 2.27 Å, 133.0°) stack along the a-axis and are connected to neighboring dimers by C−H···Cl interactions (C10− H10···Cl1, 2.64 Å, 141.3° and C15−H15···Cl2, 2.74 Å, 153.4°) (Figure 9). MCF-III. Block morphology crystals obtained from diethyl ether solved and refined in monoclinic space group C2/c with a half molecule in the asymmetric unit. Centrosymmetric dimers formed by C−H···π interactions (C11−H11···π, 2.63 Å, 154.5°)
stack along the c-axis. They are connected to neighboring dimers by bifurcated C−H···O hydrogen bonds (C12−H12B···O1, 2.69 Å, 150.4°) (Figure 10). TCF. Single crystals obtained from n-hexane afforded the crystal structure in monoclinic space group P21/n with one molecule in the asymmetric unit. The crystal structure has an entirely different molecular packing compared to other fuchsones in this series. C−H···O (C10−H10···O1, 2.27 Å, 133.9°) and Cl···Cl interactions (Cl3···Cl4, 3.48 Å, 154.8°, 102.1°) connect molecules in a sheet motif which extends through C−H···Cl (C13−H13···Cl4, 2.76 Å, 127.3°) and CO···π interactions (3.15 Å, not shown) (Figure 11). A second polymorph of TCF could not be crystallized after several crystallization attempts in different conditions. C−H···O hydrogen bonds in all crystal structures are listed in Table 3. Chloro−Methyl Exchange and Isostructurality. Crystal structures of TMF-I, CMF-I, and MCF-I show that C−H···CH3 close packing in TMF-I (C18−H18···C20, 2.83 Å, 169.8°, C3− H3···C21, 3.04 Å, 125.4° and C13−H13···C23, 2.76 Å, 141.6°) is replaced by C−H···Cl interactions in CMF-I (C18−H18···Cl1, 5415
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Figure 6. Intermolecular interactions and molecular packing in CMF-II. (a) Antiparallel C−H···O hydrogen bonded chains (C16−H16···O1, 2.50 Å, 128.2°) are connected to each other by C−H···O (C9−H9···O1, 2.19 Å, 169.8°) and C−H···Cl hydrogen bond (C21−H21C···Cl2, 2.92 Å, 143.7°). (b) C−H···Cl interactions complete the packing.
Figure 5. Structural differences of CMF-I and CMF-II. In CMF-I the two quinoid rings are offset whereas they are nearly overlapping in CMF-II. The crystal structure of CMF-II is shown in Figure 6.
2.79 Å, 169.0° and C3−H3···Cl2, 2.82 Å, 122.3°) and MCF-I (C13−H13···Cl2, 2.66 Å, 140.1°) to give isomorphous crystals (e.g., compare Figures 1, 4, and 8). Again, C−H···CH3 hydrophobic contact in CMF-I (C13−H13···C21, 2.75 Å, 146.6°) is exchanged by C−H···Cl interaction in MCF-I (C13−H13···Cl2) and C−H···CH3 contact of MCF-I (C16−H16···C20, 2.80 Å, 171.7°) is replaced by C−H···Cl interaction in CMF-I (C18− H18···Cl1). TMF-II and MCF-II are another isomorphous crystal pair in fuchsones and crystal structure analysis showed that C−H···CH3 close packing in TMF-II (C19−H19···C22, 2.84 Å, 151.4°, C10−H10···C23, 2.74 Å, 141.4°) is replaced by C−H···Cl interactions in MCF-II (C15−H15···Cl2, 2.74 Å, 153.4°, C10−H10···Cl1, 2.64 Å, 141.3°) (e.g., compare Figures 2 and 9). TCF, wherein all the methyl groups are replaced by chlorine, has crystal packing and unit cell parameters completely different from all other Me/Cl structures in this series. Cl···Cl distances
