CRYSTAL GROWTH & DESIGN
The Crystal Structure of Methyl Paraben at 118 K Does Not Represent a New Polymorph
2007 VOL. 7, NO. 11 2297
Terence L. Threlfall* and Thomas Gelbrich UniVersity of Southampton, Highfield, Southampton, SO17 1BJ, United Kingdom ReceiVed January 25, 2007; ReVised Manuscript ReceiVed August 17, 2007
ABSTRACT: The conformational differences in the structure of methyl paraben at 118 K and room temperature would appear to be within normal changes because of lattice expansion. Therefore, they do not represent different polymorphs as proposed in a publication (Vujovic, D.; Nassimbeni, L. R. Cryst. Growth Des. 2006, 6, 1595–1597). The true definition of a polymorph is that it represents a distinct solid phase and not that it represents a distinct crystal structure. The structure of a crystal changes with the temperature and pressure. The slight differences can accumulate over a large temperature or pressure interval to produce a substantial structural difference. This does not of itself produce a new phase or new polymorph. It is our experience that significant anisotropicity of the lattice expansion is the norm for organic materials.1 Polymorph I of sulfathiazole is an extreme example for which the b axis expands with the temperature more than 5 times that expected, while the a axis remains unchanged. The c axis then decreases substantially with the temperature to maintain a sensible volume expansion. These changes are shown in Table 1. The consequences of this is that the X-ray powder patterns at 150 K, room temperature, and 370 K can hardly be recognized as belonging to the same substance.2 In the Raman spectrum, the NH stretching frequency increases by 28 cm-1 between 150 K and room temperature.3 These differences are brought about by the weakening of the strongest intermolecular interactions, namely, the shortest hydrogen bonds, and a unwinding of the structure with concomitant intermolecular torsional changes around the hydrogen bonds. This is because changes to the shortest intermolecular interactions afford the most relief of vibrational crowding as the temperature increases and because the conformational changes usually require the least energy for their implementation.4 There is however no question that the polymorph I remains the same polymorph and the same phase over all temperatures up to the melting point at 475 K. Thus, one can get a change of structure without a change of phase but not a change of phase without a change of structure. The existence of distinct phases will normally be recognized either by a phase transition or by structural and property changes greatly in excess of those brought about by normal temperature expansion. In the case of methyl paraben,6 the event in the differential scanning calorimetry (DSC) at 180 K cannot represent a phase transition, because it is accompanied by no discernable structural change. The changes in the lattice parameters around 240 K are very slight. These differences may be outside the errors of measurement, although the true errors of the lattice parameter measurement are usually grossly underestimated.5 The scale of the abscissa and the absence of error bars in Figure 5 of ref 6 make a critical judgment difficult. In any case, there is no evidence for a phase change around this temperature other than the slight variation of lattice parameters, which could easily be accounted for by minor conformational changes. The fact that the DSC and the lattice parameter change cannot be the detection of * To whom correspondence should be addressed. Telephone: +44-2380596722. Fax: +44-2380-596723. E-mail:
[email protected].
Table 1. Unit-Cell Parameters of Sulfathiazole Polymorph I, with Space Group P21/c, at Various Temperatures a (Å) b (Å) c (Å) β (deg)
150 K
193 K
295 K
370 K
10.534(2) 12.936(3) 17.191(3) 107.77(3)
10.5474(2) 13.0000(4) 17.1781(4) 107.8101(8)
10.5542(7) 13.2505(8) 17.0760(12) 107.9578(23)
10.5418(4) 13.5221(6) 16.9190(8) 108.1415(20)
the same event with a temperature offset is certain because the offset is in the wrong direction; the DSC detection might occur at a higher temperature than the crystallographic detection, because of the faster time scale of the former, but cannot occur at a lower temperature. We have used the XPac program,7 which detects crystal structure similarity, to confirm that the packing in the two supposed polymorphs is identical, in agreement with the conclusions of the authors of ref 6. We have looked in detail at the slight conformational differences between the proposed structures and conclude that these are well within expectations of normal changes with temperature. Therefore, it would appear clear that no polymorphs are involved. It is the method of science to group together examples of similar properties, behavior, and phenomena and label the resulting groups to provide an identity. Thereby, a distinction is drawn from other groups. In doing so, we impose discontinuities on Nature’s continuum. There will undoubtedly then be borderline examples for which it will be difficult to state categorically whether a polymorph is the correct label or not, but we believe that this is not the case here and the changes, although large, fall within those expected for changes of the structure with temperature, without a phase change.
References (1) See also (a) van de Streek, J.; Motherwell, S. Acta Crystallogr., Sect. B: Struct. Sci. 2005, 61, 510. (b) Stephenson, G. J. Pharm. Sci. 2006, 95, 821. (2) Threlfall, T. L.; Hursthouse, M. B. Unpublished observations. (3) de Paepe, A. University of Southampton, Southampton, U.K., unpublished observations. (4) Threlfall, T. Org. Process Res. DeV. 2003, 7, 1017. (5) Vujovic, D.; Nassimbeni, L. R. Cryst. Growth Des. 2006, 6, 1595. (6) (a) Taylor, R.; Kennard, O. Acta Crystallogr., Sect. B: Struct. Sci. 1986, 42, 112–120. (b) Herbstein, F. H. Acta Crystallogr., Sect. B: Struct. Sci. 2000, 56, 547–557. (7) (a) Gelbrich, T.; Hursthouse, M. B. CrystEngComm 2005, 7, 324. (b) Gelbrich, T.; Hursthouse, M. B. CrystEngComm 2006, 8, 448.
CG0700871
10.1021/cg0700871 CCC: $37.00 2007 American Chemical Society Published on Web 10/25/2007
