CRYSTAL GROWTH & DESIGN
Methyl ParabensA New Polymorph?
2006 VOL. 6, NO. 7 1595-1597
Dejana Vujovic* and Luigi R. Nassimbeni Department of Chemistry, UniVersity of Cape Town, Rondebosch 7701, South Africa ReceiVed December 1, 2005; ReVised Manuscript ReceiVed April 26, 2006
ABSTRACT: The crystal structure of methyl paraben was elucidated at 113K (1), while the structure at room temperature (2) has been determined previously (Lin, X. T. Chin. J. Struct. Chem. 1983, 2 (3), 213). There is a slight lengthening of the b axis in the low-temperature structure and twisting of the ester group resulting in small but statistically significant differences in the PXRD patterns between 1 and 2. The phase transformation occurs gradually over the full temperature range (293-113 K). Introduction Alkyl hydroxybenzoate compounds are used in foods, drugs, and cosmetics as preservatives due to their antimicrobial properties.2 Methyl paraben, in particular, has been used extensively for more than 50 years due to its most favorable solubility properties compared to the higher chain alkyl hydroxybenzoates.2,3 Methyl paraben has also been studied for over 30 years for its potential use as a nonlinear optical material.4,5 The crystal structure of methyl paraben at room temperature has been reported and studied.1 The compound was found to crystallize in the noncentrosymmetric space group Cc with three independent molecules and Z ) 12. Here we present the results of a data collection at low temperature (113 K), which resulted in conformational changes of the ester group and changes in the calculated PXRD patterns. We believe that the results presented here represent a new conformational polymorph of methyl paraben. According to Dunitz, phase changes arise from the possibility of having the same molecule in at least two different arrangements in the solid state.6,7 When the transformation arises from the change in the shape of the molecule itself then one is dealing with a more specific case of polymorphism known as conformational polymorphism.6,7 In terms of displacive and reconstructive transformations, conformational polymorphism would belong to the former. It represents a mere distortion of one molecular arrangement into another with no major energy barrier.6,7 This is a gentler process than reconstructive change, which has a high energy barrier and requires a disruption of one structure and its reassembly into a new one.6,7 Experimental Section Crystals of 1 were prepared by dissolving methyl paraben in a minimum amount of methanol. The solution was left to evaporate slowly, and crystals were obtained after 3-4 days. X-ray intensity data were collected on a Nonius Kappa-CCD diffractometer using graphite monochromated Mo KR radiation. Temperature was controlled by an Oxford Cryostream cooling system (Oxford Cryostat). The strategy for the data collections was evaluated using the COLLECT software, scaled, and reduced with DENZOSMN software.8 The structure was solved by direct methods using SHELX-869 and refined employing full-matrix least-squares with the program SHELX-9710 refining on F2. All non-hydrogen atoms were treated anisotropically, while all hydrogen atoms bound to carbon atoms were refined with appropriate geometric constraints. The hydroxyl hydrogens of the host were refined independently without constraints. Packing diagrams were produced using the program PovRay included * To whom correspondence should be addressed. E-mail: dejana@ science.uct.ac.za. Tel.: +27 (0)21 650 2562. Fax: +27 (0)21 685 4580.
Table 1. Crystal Data and Structure Refinements for 1 and 21 compound
1
molecular formula molar mass temp (K) space group a (Å) b (Å) c (Å) R (deg) β (deg) γ (deg) volume (Å3) Z, calcd density (Mg m-3) absorption coefficient, µ (mm-1) F(000) θ range for data collection limiting indices, h, k, l reflns collected/unique data/restraints/params goodness-of-fit on F2 final R indices [I > 2σ(I)] R indices (all data) largest diff peak and hole (e Å-3)
C8H8O3 152.1 113 Cc 13.006(3) 17.261(4) 12.209(2) 90.0 129.12(3) 90.0 2126.6 12, 1.4255 0.110 960 2.15-26.38 (16, (21, (15 4338/3800 3800/2/309 1.047 R1 ) 0.0330; wR2 ) 0.0857 R1 ) 0.0402; wR2 ) 0.0902 0.20; -0.21
21 C8H8O3 152.1 298 Cc 13.568(5) 16.959(7) 12.458(6) 90.0 130.10(3) 90.0 2192.7 12, 1.382
1-28
R1 ) 0.054
in the graphic interface X-seed,11 while calculated XRD patterns were obtained using program LAZY PULVERIX.12 The DSC trace was recorded on a Perkin-Elmer Pyris1 apparatus, employing a heating rate of 20 °C min-1 and helium as the purging gas at a flow rate of 20 mL min-1.
Results and Discussion The crystal and experimental data for 1 and 2 are given in Table 1. Form 1 crystallizes in the space group Cc with Z ) 12. Three methyl paraben molecules, which are found in the asymmetric unit, are located in general positions. The packing of the molecules is shown in Figure 1 as a projection viewed along [100]. The packing of the room-temperature structure follows the same pattern, and the two seem indistinguishable. However, methyl paraben torsion angles and calculated PXRD traces for the two structures show important differences. The torsion angles, τ1 and τ2, are shown in Figure 2, and the values are presented in Table 2. The results indicate a significant twisting of the carbonyl and methyl groups of the ester in the two structures. For example, in two of the three molecules, torsion angle values τ2 differ by 4.8° and 5.9°, while three other torsion angles show a difference of between 1.1° and 1.6°. Figures 3 and 4 show superimposed and indexed calculated PXRD patterns for 1 and 2, respectively. The superimposed
10.1021/cg050639k CCC: $33.50 © 2006 American Chemical Society Published on Web 05/26/2006
1596 Crystal Growth & Design, Vol. 6, No. 7, 2006
Vujovic and Nassimbeni
Figure 3. Calculated PXRD patterns for 1 and 2.1
Figure 1. Projection of 1 down the a axis (hydrogen atoms omitted).
Figure 2. Torsion angles for the three independent methyl paraben molecules in 1 and 2.1 Table 2. Torsion Angles for 1 and τ1 (deg) molecule 1 molecule 2 molecule 3 a
1 (LT) 2 (RT)1 1 (LT) 2 (RT)1 1 (LT) 2 (RT)1
-4.3(0.2) -5.4a 1.5(0.2) 3.1a 3.0(0.2) 2.3a
|∆τ1| (deg) 1.1 1.6 0.7
Figure 4. Indexed calculated PXRD patterns for (a) 1 and (b) 2.1
21
τ2 (deg) 0.7(0.2) -4.1a 1.4(0.2) 2.8a -1.1(0.2) -7.0a
|∆τ2| (deg) 4.8 1.4 5.9
esd values not available.
PXRD traces in Figure 3 clearly show a difference between the two structures especially around 2θ values of 14°-16°, ∼18°, and 20°-24°. The indexing of the two PXRD patterns revealed that peaks corresponding to 202h and 130 are only present in the trace for structure 2, while peaks matching 311h and 150 are only present in the trace for structure 1. Further to that, two separate peaks (313h and 223h) in the trace for 2 are located at the same 2θ value and observed as one peak in the trace for 1.
We have rationalized that the contraction of a- and c-axes, volume and β angle, due to the cooling, forces a slight but significant twisting of the ester group and also forces the b axis to elongate in order to accommodate this new conformation. As a result of this twisting, there is significant difference in some of the torsion angles of the ester groups in 1 and 2 as well as PXRD patterns. We have monitored the unit cell parameters of the methyl paraben structure at various temperatures between 293 and 113 K to follow the phase transformation. The method consisted of allowing the crystal to equilibrate to a given temperature for 10 min in a stream of cold nitrogen supplied by an Oxford Cryostat and to carry out a limited data collection and determine unit cell parameters by collecting 20 frames and varying the φ angle by 1° with exposure time of 22 s. The results are shown in Figure 5. They indicate that the change in all parameters (a, b, c, β, and V) is continuous and that it occurs over the full temperature range. In the case of the b axis, which increases in
Methyl ParabensA New Polymorph?
Crystal Growth & Design, Vol. 6, No. 7, 2006 1597
observed a small endotherm (Ton ) 180.4 K, Tpeak ) 181.6 K, ∆H ) 9.2 J mol-1). We note that the enthalpy change is very small, and there is no corresponding discontinuity in the cell parameters shown in Figure 5 at the corresponding temperature. We believe that cooling of the crystal under liquid nitrogen from 293 to 113 K leads to a conformational change of methyl paraben molecules and results in the formation of a new polymorph. Acknowledgment. We thank Professor Jonathan Steed and Mr. Doug Carswell, Department of Chemistry, University of Durham (U.K.), for carrying out the DSC experiments. Supporting Information Available: Crystallographic information (CIF format). This material is available free of charge via the Internet at http://pubs.acs.org.
References
Figure 5. Changes in cell parameters (a, b, c, β, and V) with temperature (293-113 K).
size with decreasing temperature, most of the change occurs between 293 and 243 K. A phase change is usually accompanied by a change in the molar volume of the solid and a measurable change in the molar enthalpy of the compound. Accordingly we have run a DSC trace from 93 to 273 K at a heating rate of 20 °C min-1 and
(1) Lin, X. T. Chin. J. Struct. Chem. 1983, 2 (3), 213. (2) Soni, M. G.; Taylor, S. L.; Greenberg, N. A.; Burdock, G. A. Food Chem. Toxicol. 2002, 40, 1335. (3) Giordano, F.; Bettini, R.; Donini, C.; Gazzaniga, A.; Caira, M. R.; Zhang, G. G. Z.; Grant, D. J. W. J. Pharm. Sci. 1999, 88, 1210. (4) Zhengdong, L.; Baichang, W.; Genbo, S. J. Cryst. Growth 1997, 178, 539. (5) Lakshmana Perumala, C. K.; Arulchakkaravarthia, A.; Santhanaraghavanb, P.; Ramasamya, P. J. Cryst. Growth 2002, 241, 200. (6) Dunitz, J. D. Acta Crystallogr. 1995, B51, 619. (7) Dunitz, J. D. Pure Appl. Chem. 1991, 63, 177. (8) Otwinowski, Z.; Minor, W. In Methods in Enzymology - Macromolecular Crystallography; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: New York, 1997; Part A, Vol. 276, pp 307-326. (9) Sheldrick, G. M. In SHELX-86: Crystallographic Computing; Sheldrick, G. M., Kruger C., Goddard, R., Eds.; Oxford University Press: Oxford, U.K., 1985; Vol. 3, p175. (10) Sheldrick, G. M. SHELX-97: Program for Crystal Structure Refinement; University of Go¨ttingen: Germany, 1997. (11) Barbour, L. J. J. Supramol. Chem. 2001, 1, 189. (12) Yvon, K.; Jeitschko, W.; Parthe, E. J. Appl. Crystallogr. 1977, 10, 353.
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