Comment

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.

Experimental

A single-crystal sample of the title compound was recrystallized from a saturated N-methylpyrrolidone solution by isothermal solvent evaporation at 298 K.

Crystal data

C7H8ClN3O4S2·2C5H9NO Mr = 496.00 Monoclinic, P 21 /c a = 17.0756 (6) Å b = 7.4819 (3) Å c = 17.9978 (6) Å = 105.211 (2)° V = 2218.81 (14) Å3 Z = 4 Dx = 1.485 Mg m-3 Mo K radiation = 0.41 mm-1 T = 123 (2) K Cut from prism, colourless 0.32 × 0.20 × 0.12 mm

Data collection

Nonius KappaCCD area-detector diffractometer and scans Absorption correction: none 24804 measured reflections 4852 independent reflections 3673 reflections with I > 2(I) Rint = 0.093 max = 27.1°

Refinement

Refinement on F2 R[F2 > 2(F2)] = 0.064 wR(F2) = 0.174 S = 1.08 4852 reflections 296 parameters H atoms treated by a mixture of independent and constrained refinement w = 1/[2(Fo2) + (0.1041P)2 + 0.892P] where P = (Fo2 + 2Fc2)/3 (/)max = 0.001 max = 0.70 e Å-3 min = -0.55 e Å-3

Table 1 Hydrogen-bond geometry (Å, °) D-HA D-H HA DA D-HA N1-H1NO6i 0.79 (5) 2.01 (5) 2.799 (4) 177 (5) N2-H2NO6ii 0.80 (4) 2.35 (4) 2.929 (4) 130 (3) N3-H3NO5 0.84 (3) 2.12 (4) 2.891 (4) 153 (4) N3-H4NO5iii 0.86 (4) 2.04 (4) 2.884 (4) 169 (3) C1-H1AO6ii 0.99 2.58 3.075 (4) 111 C7-H7O2iv 0.95 2.33 3.249 (4) 164 C11-H11BO3v 0.99 2.52 3.423 (4) 152 Symmetry codes: (i) -x+1, -y+1, -z; (ii) ; (iii) ; (iv) x, y+1, z; (v) .

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 U_iso(H) = 1.5U_eq(C) for methyl H atoms and U_iso(H) = 1.2U_eq(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.