Received 20 September 2006
aSolid State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, and bWestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland
Correspondence e-mail: firstname.lastname@example.org
Hydrochlorothiazide forms a 1:2 solvate with N-methylpyrrolidone (systematic name: 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide N-methyl-2-pyrrolidone disolvate), C7H8ClN3O4S2·2C5H9NO. The compound crystallizes with one hydrochlorothiazide and two solvent molecules, one of which is disordered, in the asymmetric unit. The crystal structure is isostructural with the previously reported hydrochlorothiazide N,N-dimethylacetamide disolvate.
Hydrochlorothiazide (HCT) is a thiazide diuretic which is known to crystallize in at least two non-solvated forms, form I (Dupont & Dideberg, 1972) and form II (Florence et al., 2005). The title compound of this report, (I), was produced during an automated parallel crystallization study of HCT (Johnston, Florence, Shankland et al., 2006). The sample was identified as a novel form using multi-sample foil transmission X-ray powder diffraction analysis (Florence et al., 2003). Subsequent manual recrystallization from a saturated N-methylpyrrolidone (NMP) solution by slow evaporation at 298 K yielded samples of (I) suitable for single-crystal diffraction (Fig. 1).
It is notable that the crystal structure of (I) is isostructural with that of the previously reported HCT N,N-dimethylacetamide (DMA) disolvate (Johnston, Florence & Kennedy, 2006), with the same space group and very similar unit-cell parameters and packing arrangements. Adjacent HCT chains pack as layers in the ab plane and form an alternating stacked arrangement with layers of solvent molecules in the direction of the c axis (Fig. 2). The structures differ slightly in the extent of solvent disorder, with both solvent molecules disordered in the HCT-DMA disolvate, compared with a single molecule in (I). The structure also contains four N-HO hydrogen bonds, with N1, N2 and N3 of HCT donating contacts to adjacent O atoms of NMP (Table 1).
| || Figure 1 |
The asymmetric unit contents of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Minor disorder components have been omitted for clarity.
| || Figure 2 |
The crystal packing in the structure of (I), viewed down the b axis, showing the alternating layers of HCT and NMP molecules.
A single-crystal sample of the title compound was recrystallized from a saturated N-methylpyrrolidone solution by isothermal solvent evaporation at 298 K.
Three C atoms (C14, C15 and C16) and the associated H atoms of one solvent molecule were treated as disordered over two sites. Isotropic refinement gave a refined occupancy of 0.52 (3):0.48 (3). All amine H atoms were found by difference synthesis and refined isotropically. All other H atoms were positioned geometrically at distances of 0.95 (CH), 0.98 (CH3) or 0.99 Å (CH2); a riding model was used during refinement, with Uiso(H) = 1.5Ueq(C) for methyl H atoms and Uiso(H) = 1.2Ueq(C) for all others.
Data collection: COLLECT (Nonius, 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: ORTEPII (Johnson, 1976); 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 (http://www.cposs.org.uk ).
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Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.