Received 23 June 2005
Hydrochlorothiazide forms a 1:1 solvate with aniline, C7H8ClN3O4S2·C6H7N. The crystal structure contains a hydrogen-bonding network comprising two N-HN and three N-HO contacts.
Hydrochlorothiazide (HCT) is a thiazide diuretic which is known to crystallize in at least one non-solvated form (Dupont & Dideberg, 1972). The aniline solvate, (I), was produced during an automated parallel crystallization polymorph screen on HCT. The sample was identified as a novel form using multisample X-ray powder diffraction analysis of all recrystallized samples (Florence et al., 2003). Subsequent manual recrystallization from a saturated 1:1 acetone-aniline solution by slow evaporation at 278 K yielded samples of (I) suitable for single-crystal X-ray analysis (Fig. 1).
In (I), the N1-S1-C1-N2-C2-C7 six-membered ring in HCT adopts a non-planar conformation, with atoms S1 and N1 having deviations of 0.271 (1) and 0.843 (1) Å, respectively, from the least-squares plane through atoms C2-C7. The sulfonamide side chain adopts a torsion angle N3-S2-C5-C4 of 69.05 (12)°, such that atom O4 eclipses H6 and atoms O3 and N3 are staggered with respect to Cl1. In the non-solvated structure (Dupont & Dideberg, 1972), this group is rotated by approximately 130° compared to (I) such that the amine group lies on the opposite side of the benzothiadiazine moiety. The aniline molecule is planar, the greatest deviation of any non-H atom from the least-squares plane through C8-C13/N4 being 0.013 (1) Å for C8.
The crystal structure is stabilized by a network of hydrogen bonds interconnecting (a) HCT molecules (Fig. 2, contacts 1 and 2) and (b) HCT and solvent molecules (contacts 3, 4 and 5). Two C-HO contacts also exist between HCT molecules (contacts 6 and 7). Contact 1 (N3-H3NO2) forms a centrosymmetric R22(16) motif between molecules of HCT, whilst contacts 4 and 5 (N4-H5NN3 and N4-H6NO4) combine to form an R44(12) motif between aniline and HCT (Fig. 3). Hydrophobic interactions between HCT and aniline include a C-H contact and an offset face-to-face (off) - approach (Fig. 4).
| || Figure 1 |
Plot of the asymmetric unit contents with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
| || Figure 2 |
A packing diagram of (I). Dashed lines indicate hydrogen bonds and unique contacts are labelled as follows: 1 = N3O2 [2.9725 (16) Å, O2 in the molecule at (1 - x, 1 - y, 2 - z)]; 2 = N3O1 [2.9390 (15) Å, O1 in the molecule at ( + x, - y, - + z)]; 3 = N1N4 [2.9652 (17) Å]; 4 = N4N3 [3.3944 (18) Å, in the molecule at (-1 + x, y, z)]; 5 = N4O4 [3.1000 (17) Å, O4 in the molecule at (1 - x, 1 - y, 2 - z)]; 6 = C1O3 [3.2535 (18) Å, O3 in the molecule at (1 - x, -y, 2 - z)]; 7 = C1O3 [3.2852 (17) Å, O3 in the molecule at (-1 + x, y, z)]. Contacts calculated and illustrated using PLATON (Spek, 2003; program version 280604)
| || Figure 3 |
The R22(16) (left) and R44(12) hydrogen-bond motifs in the crystal structure of (I).
| || Figure 4 |
Hydrophobic interactions in (I), showing a C3-H3centroid contact to the centroid of the benzene ring of aniline [C3centroid = 3.618 (2) Å] (top) and a - off-stacking interaction between HCT and aniline with a centroid-centroid distance of 3.6955 (8) Å (bottom). Contacts are illustrated using dashed lines.
A single-crystal sample of the title compound was recrystallized from a 1:1 acetone-aniline solution by slow evaporation at 278 K.
The N-bound H atoms were found in difference maps and refined freely [N-H = 0.77 (2)-0.90 (2) Å]. The remaining H atoms were positioned geometrically at distances of 0.95 (CH) and 0.99 Å (CH2) from the parent C atoms; a riding model was used [Uiso(H) = 1.2Ueq(C)] during the refinement process.
Data collection: COLLECT (Hooft, 1988) and DENZO (Otwinowski & Minor, 1997); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.
The authors thank the Basic Technology programme of the UK Research Councils for funding this work under the project Control and Prediction of the Organic Solid State (URL: www.cposs.org.uk).
Dupont, L. & Dideberg, O. (1972). Acta Cryst. B28, 2340-2347.
Florence, A. J., Baumgartner, B., Weston, C., Shankland, N., Kennedy, A. R., Shankland, K. & David, W. I. F. (2003). J. Pharm. Sci. 92, 1930-1938.
Hooft, R. (1988). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.