Crystallization through Slow Acid-Controlled Hydrolytic Release of a Highly Polar Organic Compound: Formation of a Dipolar Acridone Polymorph Xuefeng Mei and Christian Wolf* Department of Chemistry, Georgetown University, Washington, DC 20057 Received April 7, 2005;
CRYSTAL GROWTH & DESIGN 2005 VOL. 5, NO. 5 1667-1670
Revised Manuscript Received June 10, 2005
ABSTRACT: A new polymorph of acridone exhibiting a highly ordered dipolar crystal structure was prepared by slow fumaric acid-controlled hydrolysis of its bromoacridine precursor in ethanol. Organic nonlinear optical materials have attracted considerable attention because of their potential applications as frequency-shifting devices and optical modulaters and switches in the emerging fields of telecommunication, data storage, and signal processing technologies.1 To date, a variety of nonlinear optics (NLO) exhibiting large second harmonic generation or electrooptical activity has been developed through careful design of organic molecular building blocks.2 Second-order nonlinear effects arise from nonzero microscopic hyperpolarizability, β, and macroscopic susceptibility, χ, tensors. This can be achieved when neutral dipolar organic chromophores exhibiting significantly different dipole moments in their ground and excited states can be arranged in a noncentrosymmetric crystal lattice, Langmuir-Blodgett layers, or polymeric materials. Intermolecular charge transfer between centrosymmetric molecules that are arranged in a noncentrosymmetric manner has also been found to result in second harmonic generation.3 The formation of nonlinear optical supramolecular assemblies from polar aromatic molecules that exhibit push-pull conjugation and the ability to participate in hydrogen bonding, dipole-dipole interactions, and π-stacking has become a powerful strategy in crystal engineering.4 Noncentrosymmetric crystal growth of dipolar compounds has been achieved by increasing the molecular asymmetry of selectively substituted aromatic compounds, which favors nonsymmetric intermolecular hydrogen bonding, and by employing nonracemic chiral molecules or organometallic salts in crystallization experiments.2 Despite the potential of highly polar and zwitterionic aromatic organic compounds as promising candidates for the development of NLO, the control of single-crystal growth and the feasibility of macroscopic nonlinear properties are often hampered by the inherently low solubility and the pronounced tendency of compounds such as acridone to form centrosymmetric, antiparallel molecular arrangements in order to reduce electrostatic repulsion in the solid state.5 We wish to report a new approach for the preparation of single crystals of acridone exhibiting very low solubility in organic solvents through slow acid-controlled hydrolysis of a soluble precursor. We found that slow hydrolysis of bromoacridine results in the formation of a new dipolar polymorph of acridone exhibiting second-order optical nonlinearity. It is well-known that 9(10H)-acridone, 1, affords considerable zwitterionic character, which can be described by resonance structures 1a and 1b. In addition, 1 easily tautomerizes to 9-hydroxyacridine, 2, Scheme 1. Because of its highly polar structure and ability to undergo hydrogen bonding, 1 affords promising molecular properties for the development of solid organic materials. However, the low solubility in organic solvents impedes efforts to control singlecrystal growth of 1. To date, only one crystal structure of * E-mail:
[email protected].
Figure 1. Single-crystal X-ray analysis of 1 generated via acidmediated hydrolysis of 3. Asymmetric unit of 9(10H)-acridone form II selective bond lengths (Å) and bond angles (deg) are as follows: O(1)-C(9), 1.296; O(2)-C(22), 1.285; N(1)‚‚‚O(2), 2.769; N(2)‚‚‚O(1), 2.753; N(1)-H(1N)‚‚‚O(2), 167.26; N(2)-H(2N)‚‚‚O(1), 165.00.
Scheme 1.
Resonance Structures and Tautomerism of 9(10H)-Acridone, 1
1, in which hydrogen bonding and π-π interactions result in a centrosymmetric herringbone packing arrangement of antiparallel chains of 9(10H)-acridone, has been reported.6 Interestingly, the C-O bond length was determined as 1.25 Å indicating the significance of resonance structure 1b.7 From our experience with 9-chloro- and 9-bromoacridines that we had previously prepared for other purposes, we knew that these compounds undergo acid-catalyzed hydrolysis in the presence of small amounts of water to give the corresponding hydroxyacridines.8 We also observed that bromoacridines easily dissolve in a variety of organic solvents and are more stable to hydrolysis than the chlorides. 9-Bromoacridine, 3, was therefore chosen as a source for slow acid-mediated generation of acridinol 2 and subsequent formation of tautomer 1. A continuous formation of small amounts of acridone in an organic solvent would
10.1021/cg050136e CCC: $30.25 © 2005 American Chemical Society Published on Web 07/19/2005
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Figure 2. Single-crystal structure and polarity of known polymorph I (left) and new polymorph II (right). Table 1. Selected Crystallographic Data of Acridone Polymorphs I and II crystal system space group temp (K) a (Å) b (Å) c (Å) R (deg) β (deg) γ (deg) cell volume (Å3) calcd density (g/cm3) Z µ (Mo KR) unique reflns Rint
form I
form II
monoclinic P21/n 296(2) 4.533(1) 16.537(3) 12.687(3) 90 97.22(3) 90 943.5(3) 1.374 4 0.710 73 1664 0.0296
triclinic P1 184(2) 4.761(2) 8.539(4) 12.086(6) 105.425(7) 93.311(9) 99.888(8) 463.84 1.398 2 0.710 73 3133 0.0501
avoid difficulties resulting from the inherently low solubility of 1 and provide new means to allow slow growth of acridone single crystals. We recently reported the use of dicarboxylic acids as templates for the preparation of new polymorphs of acridine and therefore employed various acids in our crystallization efforts.9 We found that careful cooling of a heated solution of 3 in ethanol containing 5% water and 50% fumaric acid results in the formation of colorless plates. Since 3 crystallizes in the form of brown needles, the change in color and crystal morphology seemed indicative of acridyl halide hydrolysis. Indeed, X-ray analysis of the new crystals revealed acridone formation, Figure 1. We were pleased to find that our crystal growing method yielded a unique single-crystal structure exhibiting parallel dipolar chains consisting of almost perpendicular molecules of 1 stabilized through hydrogen bonding, Figure 2. Crystallographic analysis revealed that the crystal is triclinic and belongs to the P1 space group. The unit-cell dimensions and other X-ray data are shown in Table 1. Interestingly, N‚‚‚O distances are 2.769 and 2.753 Å, and the closest contact between parallel acridyl moieties from two adjacent chains was determined as 3.425 Å showing the significance of hydrogen bonding and π-π interactions. The C-O bond lengths proved to be 1.285 and 1.296 Å indicating considerable zwitterionic character of 1. Thermogravimetric analysis and DSC measurements showed that this new polymorph of acridone does not undergo phase transition or melting prior to decomposition above 250 °C, which was also observed with amorphous acridone. Neutral dipolar organic compounds are well-known to form two-dimensional packing motifs such as noncentrosymmetric chains
Figure 3. Single-crystal structure of acridone polymorph II showing the three-dimensional parallel packing of dipolar acridone sheets. The closest contact between the parallel acridone rings is 3.425 Å.
or sheets. However, the pronounced tendency of polar compounds to crystallize in dipolar chains or sheets with antiparallel orientation diminishes NLO properties of these materials.10 Crystal engineering strategies toward NLO exhibiting a parallel alignment of polar sheets have therefore relied on the use of organic salts. This approach requires mediating anionic sheets for stabilization of parallel polar sheets, that is., an alternating arrangement of cationic and anionic sheets is utilized to facilitate formation of polar crystals.11 By contrast, we observed that the dipolar chains of 1 in this new polymorph are parallel throughout the whole crystal lattice. We thus obtained a highly dipolar single crystal exhibiting a unique three-dimensional packing motif, that is, a parallel alignment of polar sheets of acridone that renders the introduction of counterionic sheets unnecessary, Figure 3. We assume that slow acidic hydrolysis of 3 provides a steady supply of 2 for subsequent crystallization. Efforts to prepare single crystals of acridone directly from dichloromethane, chloroform, acetonitrile, ethyl acetate, toluene, and 2-propanol, ethanol, and DMF were hampered by the inherently low solubility of acridone and unsuccessful. However, polymorph II was prepared reproducibly from 9-bromoacridine when fumaric acid was employed in an
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Proposed Acid-Mediated Hydrolysis of 9-Bromoacridine, 3, and Subsequent Growth of Polymorph II
ethanolic solution.12 Attempts to grow single crystals of acridone via hydrolysis of 3 using other carboxylic acids, for example acrylic, trans-cinnamic, maleic, terephthalic, or trans,trans-muconic acid, and hydrochloric or sulfuric acid in aqueous ethanol were unsuccessful. The use of fumaric acid thus seems crucial for the preparation of the new polymorph. Although the role of fumaric acid is not clear, it may favor formation of zwitterionic 1 via protonation of the acridyl nitrogen atom and function as a template during the nucleation and crystallization processes, Scheme 2. Thus, fumaric acid might not only mediate the hydrolysis of 3 but also play an important role in the formation of polymorph II exhibiting a single dipolar crystal with a highly ordered structure of parallel polar chains of 1. Slow acid-controlled generation of highly insoluble polar compounds combined with template-mediated crystallization may thus provide a new tool for crystal engineering of solid organic materials exhibiting NLO activity.13 Calculated powder X-ray diffractions of both polymorphs and XRD patterns experimentally acquired from crystalline materials obtained by hydrolysis of 9-bromoacridine are shown in Figure 4. The computated powder X-ray diffractions of form II (computations were based on single-crystal data obtained at 184 K) are almost identical to the experimentally obtained XRD patterns (298 K), which demonstrates that the bulk material has the same structure as the single crystal. It should be noted that lowering the temperature changes the dimensions of the crystal lattice, which can be expected to result in shifting of the corresponding XRD patterns. By contrast, comparison of the calculated XRD patterns of form I (296 K) with the powder diffractions of form II reveals significant differences at both low and high diffraction angles. The XRD data collected from crystalline materials prepared by fumaric acid mediated hydrolysis of 9-chloroacridine (298 K) suggests forma-
tion of polymorph II. However, comparison of the XRD patterns obtained from both haloacridines shows significant discrepancies. This indicates that the bulk material obtained from the rapidly hydrolyzing 9-chloroacridine is not pure or that another polymorph has been formed. Experimental Section. Preparation of Acridone Polymorph II. A solution of 9-bromoacrdine (129 mg, 0.5 mmol) and fumaric acid (29 mg, 0.25 mmol) was heated in 5 mL of ethanol containing 5% water until dissolved. Slow evaporation of the solution gave colorless thin plate crystals after 24 h. Crystallography. X-ray diffractions of a single crystal (0.5 × 0.5 × 0.01 mm3) were performed at -89 °C using a Siemens P4 single-crystal platform diffractometer with graphite monochromated Mo KR radiation (λ ) 0.710 73 Å). The structures were solved by direct methods and refined with full-matrix least-squares difference Fourier analysis using SHELX-97-2 software. Nonhydrogen atoms were refined with anisotropic displacement parameters, and all hydrogen atoms were placed in calculated positions and refined with a riding model. Data were corrected for the affects of absorption using SADABS. Powder X-ray Diffraction. Samples of form II obtained from 9-chloro- and 9-bromoacridine were finely ground and packed in a 0.3-0.5 mm glass tube, and the tubes were then sealed. Powder diffraction X-ray patterns were obtained with a Rigaku RAPID Curved IP X-ray diffractometer coupled with a Cu KR radiation tube (V ) 46 kV and I ) 46 mA). A 0.8 mm collimator was used; 2θ was scanned on a range of 3.5-60°. All data were acquired at ambient temperature. Data were imaged and integrated with RINT Rapid and peak-analyzed with Jade 5.0 software from Rigaku. A fit background subtraction was conducted with all XRD patterns. Acknowledgment. We thank Edward Van Keuren, Department of Physics at Georgetown University, for the determination of the second-order susceptibility of polymorph II.
References
Figure 4. Powder X-ray diffraction patterns of the two polymorphs of acridinone 1: (a) calculated diffraction pattern of form II (based on single-crystal data, 184 K); (b) experimentally obtained powder diffraction pattern of form II obtained from 9-bromoacridine (298 K); (c) experimental powder pattern of form II obtained from 9-chloroacridine (298 K); (d) calculated powder X-ray diffraction of polymorph I (single-crystal data taken from Potts and Jones6). Significant differences between the two polymorphs are indicated by asterisks.
(1) Chemla, D. S., Zyss, J., Eds. Nonlinear Optical Properties of Organic Molecules and Crystals; Academic Press: New York, 1987; Vols. 1 and 2. (2) (a) Marder, S. R.; Perry, J. W.; Schaefer, W. P. Science 1989, 245, 626-628. (b) Marder, S. R.; Perry, J. W.; Tiemann, B. G. Chem. Mater. 1990, 2, 685-690. (c) Marder, S. R.; Perry, J. W.; Tiemann, B. G. Organometallics 1991, 10, 1896-1901. (d) Marder, S. R.; Perry, J. W.; Yakymyshyn, C. P. Chem. Mater. 1994, 6, 1137-1147. (e) Kagawa, H.; Sagawa, M.; Hamada, T.; Kakuta, A. Chem. Mater. 1996, 8, 2622-2627. (f) Lochran, S.; Bailey, R. T.; Cruickshank, F. R.; Pugh, D.; Sherwood, J. N.; Simpson, G. S. Langley, P. J.; Wallis, J. D. J. Phys. Chem. B 2000, 104, 6710-6716. (g) Pal, T.; Kar, T.; Bocelli, G.; Rigi, L. Cryst. Growth Des. 2003, 3, 13-16. (3) Ashwell, G. J.; Jefferies, G.; Hamilton, D. G.; Lynch, D. E.; Roberts, M. P. S.; Bahra, G. S.; Brown C. R. Nature 1995, 375, 385-388.
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(4) (a) Cheng, L.-T.; Tam, W.; Stevenson, S. H.; Meredith, G. R. J. Phys. Chem. 1991, 95, 10631-10643. (b) Zyss, J.; Ledoux, I. Chem. Rev. 1994, 94, 77-105. (c) Aakeroy, C. B.; Beatty, A. M.; Tremayne, M.; Rowe, D. M.; Seaton, C. C. Cryst. Growth Des. 2001, 1, 377-382. (d) Hulliger, J.; Bebie, H.; Kluge, S.; Quintel, A. Chem. Mater. 2002, 14, 1523-1529. (5) Facchetti, A.; v.-d. Boom, M. E.; Abbotto, A.; Beverina, L.; Marks, T. J.; Pagani, G. A. Langmuir 2001, 17, 5939-5942. (6) Potts, G. D.; Jones, W. Acta Crystallogr. 1995, C51, 267-268. (7) For comparison, a search of the Cambridge Crystallographic Data Centre (CCDC) database gave bond lengths of 1.20 Å (CdO) and 1.35-1.39 Å (phenolic C-O). (8) (a) Wolf, C.; Mei, X. J. Am. Chem. Soc. 2003, 125, 1065110658. (b) Mei, X.; Wolf, C. J. Am. Chem. Soc. 2004, 126, 14736-14737. (c) Mei, X.; Wolf, C. Chem. Commun. 2004, 2078-2079. (9) Mei, X.; Wolf, C. Cryst. Growth Des. 2004, 4, 1099-1103. (10) (a) Panunto, T. W.; Urbanczyk-Lipkowska, Z.; Johnson, R.; Etter, M. C. J. Am. Chem. Soc. 1987, 109, 7786-7797. (b) Etter, M. C.; Frankenbach, G. M. Chem. Mater. 1989, 1, 10-
Communications 12. (c) Lehn, J.; Mascal, M.; Cian, A. D.; Fischer, J. J. Chem. Soc., Chem. Commun. 1990, 479. (d) Etter, M. C. J. Phys. Chem. 1991, 95, 4601-4610. (11) (a) Okada, S.; Masaki, A.; Matsuda, H.; Nakanishi, H.; Kato, M.; Muramatsu, R.; Otsuka, M. Jpn. J. Appl. Phys. 1990, 29, 1112-1115. (b) Marder, S. R.; Perry, J. W.; Schaefer, W. P. Chem. Mater. 1992, 9, 985-986. (12) No single crystals were obtained with 9-bromo-4-methylacridine, 9-bromo-4-isopropylacridine, and 9-bromo-3-(3′,5′dimethylphenyl)acridine under the same conditions. (13) A crystal of polymorph II (1.00 × 0.84 × 0.22 mm3) was employed in second harmonic generation measurements. The second harmonic generation of the incident pulses from a Nd:YAG laser (wavelength 1064 nm) was measured using the Maker fringe technique. The macroscopic second-order susceptibility, χ, of form II was determined through fringe measurements and comparison to a quartz sample as 37 × 10-9 esu.
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