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Acta Cryst. (2007). E63, o3956    [ doi:10.1107/S1600536807039931 ]

Hydroflumethiazide dimethyl sulfoxide disolvate

P. Fernandes, A. Johnston, C. K. Leech, K. Shankland, W. I. F. David and A. J. Florence

Abstract top

Hydroflumethiazide forms a 1:2 solvate with dimethyl sulfoxide [systematic name: 3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide dimethyl sulfoxide disolvate], C8H8F3N3O4S2·2C2H6OS. The compound crystallizes with two molecules of solvent and one molecule of hydroflumethiazide in the asymmetric unit and displays an extensive network of hydrogen bonds. One solvent molecule is disordered over two positions, with site occupancy factors 0.57 (1) and 0.43 (1).

Comment top

Hydroflumethiazide (HFMT) is a thiazide drug that is indicated in the management of hypertension and is known to crystallize in at least one non-solvated form (Florence et al., 2003). This work forms part of a wider investigation that couples automated parallel crystallization (Florence et al., 2006) with crystal structure prediction methodology to investigate the basic science underlying solid-state diversity in a range of thiazide diuretic compounds (Johnston et al., 2007, Fernandes et al., 2007). 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 dimethyl sulfoxide solution (DMSO) by slow evaporation at 278 K yielded samples of the title compound suitable for single-crystal X-ray diffraction at 150 K (Fig. 1). The compound crystallizes with one molecule of HFMT and two molecules of DMSO in the asymmetric unit. One of the solvent molecules (residue C) is disordered over two sites with 0.43 (1) and 0.57 (1) occupancy, respectively.

The structure contains four N—H···O bonds (Table 1), with all available hydrogen-bond donors in HFMT forming contacts to adjactent sulfinyl O-atoms of DMSO. Contacts 2, 3 and 4 combine to create an R32(18) hydrogen-bonded motif (Etter, 1990) between HFMT and DMSO residue B, whilst contact 1 connects residue C to HFMT (Fig. 2).

Related literature top

For details of the experimental methods used to obtain this form of the title compound, see: Florence et al. (2003, 2006). For the crystal structures of hydroflumethiazide and of polymorphs and solvates of the related thiazide compounds chlorothiazide and hydrochlorothiazide, see: Florence et al. (2003), Fernandes et al. (2007); Johnston et al. (2007). For other related literature, see: Etter (1990).

Experimental top

The compound was sourced from Sigma–Aldrich and a single-crystal sample of the title compound was recrystallized from a saturated dimethyl sulfoxide solution by isothermal solvent evaporation at room temperature.

Refinement top

All non-hydrogen atoms were identified by direct methods and the positions of all the hydrogen atoms were obtained from the use of difference Fourier maps. In the final refinement, all hydrogen atoms were constrained to geometrically sensible positions with a riding model, except for H2, H3 and H8 which were allowed to refine subject to a distance restraint.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003), ORTEP-3 (Farrugia, 1997) and Cerius2 (Accelrys, 2001); software used to prepare material for publication: enCIFer (Allen et al., 2004) and publCIF (Westrip, 2007).

Figures top
[Figure 1] Fig. 1. The asymmetric unit of the title compound, showing 50% probablility displacement ellipsoids. Minor occupancy disordered atomic sites (residue C) have been omitted for clarity.
[Figure 2] Fig. 2. The R32(18) hydrogen-bond motif in the title compound, involving HFMT and solvent residue C. Hydrogen bond 1 (Table 1) connects solvent residue B to HFMT. Minor disorder components have been omitted for clarity.
3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide dimethyl sulfoxide disolvate top
Crystal data top
C8H8F3N3O4S2·2C2H6OSF000 = 1008
Mr = 487.55Dx = 1.609 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 8339 reflections
a = 5.55700 (10) Åθ = 2.5–28.6º
b = 20.8433 (4) ŵ = 0.53 mm−1
c = 17.4142 (3) ÅT = 150 (2) K
β = 93.540 (2)ºNeedle, colourless
V = 2013.17 (6) Å30.30 × 0.04 × 0.04 mm
Z = 4
Data collection top
Oxford Diffraction Gemini
diffractometer		4097 independent reflections
Radiation source: Enhance (Mo) X-ray source3125 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.039
T = 150(2) Kθmax = 26.4º
φ and ω scansθmin = 2.5º
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2006)		h = −6→6
Tmin = 0.917, Tmax = 1.000k = −25→26
20791 measured reflectionsl = −21→21
Refinement top
Refinement on F2Secondary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.097  w = 1/[σ2(Fo2) + (0.0499P)2 + 0.661P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
4097 reflectionsΔρmax = 0.64 e Å−3
279 parametersΔρmin = −0.35 e Å−3
3 restraintsExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C8H8F3N3O4S2·2C2H6OSV = 2013.17 (6) Å3
Mr = 487.55Z = 4
Monoclinic, P21/cMo Kα
a = 5.55700 (10) ŵ = 0.53 mm−1
b = 20.8433 (4) ÅT = 150 (2) K
c = 17.4142 (3) Å0.30 × 0.04 × 0.04 mm
β = 93.540 (2)º
Data collection top
Oxford Diffraction Gemini
diffractometer		4097 independent reflections
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2006)		3125 reflections with I > 2σ(I)
Tmin = 0.917, Tmax = 1.000Rint = 0.039
20791 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0403 restraints
wR(F2) = 0.097H atoms treated by a mixture of
independent and constrained refinement
S = 1.04Δρmax = 0.64 e Å−3
4097 reflectionsΔρmin = −0.35 e Å−3
279 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R– factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
S1−0.01352 (11)0.13727 (3)0.55321 (3)0.01901 (15)
S20.35866 (11)0.10571 (3)0.84249 (3)0.01901 (15)
S30.60374 (14)−0.07563 (3)0.67961 (4)0.03297 (19)
F30.8236 (3)0.18575 (7)0.84137 (8)0.0287 (4)
F20.5879 (3)0.26592 (7)0.85879 (9)0.0324 (4)
O30.1426 (3)0.06775 (8)0.83638 (10)0.0239 (4)
F10.8528 (3)0.27104 (8)0.77485 (9)0.0373 (4)
O40.4004 (3)0.14679 (8)0.90741 (9)0.0255 (4)
O60.2205 (3)−0.18457 (9)0.94408 (11)0.0285 (4)
O10.0979 (3)0.08578 (8)0.51422 (10)0.0263 (4)
O2−0.2453 (3)0.12674 (9)0.58203 (10)0.0260 (4)
O50.4708 (4)−0.05271 (10)0.74696 (11)0.0379 (5)
N10.3378 (4)0.24697 (11)0.54436 (12)0.0240 (5)
H70.41920.28290.54060.036*
N2−0.0319 (4)0.19850 (10)0.49524 (12)0.0229 (5)
N30.5777 (4)0.05525 (11)0.84224 (13)0.0220 (5)
C20.5116 (4)0.20571 (11)0.74488 (14)0.0186 (5)
C60.3410 (4)0.21632 (12)0.61364 (14)0.0186 (5)
C30.3592 (4)0.15283 (11)0.75733 (13)0.0178 (5)
C40.1986 (4)0.13402 (11)0.69812 (13)0.0180 (5)
H40.09200.09940.70610.027*
C80.6924 (5)0.23187 (13)0.80502 (14)0.0237 (6)
C70.2046 (5)0.22208 (13)0.47697 (14)0.0265 (6)
H60.29710.18670.45490.040*
H50.18480.25640.43780.040*
C50.1887 (4)0.16436 (12)0.62726 (13)0.0178 (5)
C10.4980 (4)0.23682 (12)0.67517 (14)0.0206 (5)
H10.59750.27320.66840.031*
C90.8253 (6)−0.01685 (16)0.66462 (18)0.0431 (8)
H9A0.9498−0.01830.70700.065*
H9B0.75020.02570.66260.065*
H9C0.8989−0.02540.61590.065*
C100.4173 (6)−0.0605 (2)0.59702 (18)0.0577 (11)
H10A0.2706−0.08640.59830.087*
H10B0.5028−0.07170.55130.087*
H10C0.3742−0.01490.59520.087*
S4A0.1219 (17)−0.1206 (5)0.9641 (6)0.0344 (13)0.432 (13)
C11A−0.0889 (18)−0.1033 (5)0.8846 (7)0.058 (3)*0.432 (13)
H11A−0.1920−0.14080.87390.088*0.432 (13)
H11B−0.0009−0.09320.83900.088*0.432 (13)
H11C−0.1890−0.06660.89740.088*0.432 (13)
C12A0.3508 (16)−0.0662 (3)0.9396 (4)0.0231 (19)*0.432 (13)
H12A0.4946−0.07260.97420.035*0.432 (13)
H12B0.2929−0.02210.94470.035*0.432 (13)
H12C0.3913−0.07380.88640.035*0.432 (13)
S4B0.0685 (12)−0.1247 (4)0.9465 (4)0.0275 (8)0.568 (13)
C12B0.2631 (15)−0.0585 (3)0.9532 (4)0.0408 (18)*0.568 (13)
H12D0.3652−0.06131.00100.061*0.568 (13)
H12E0.1683−0.01890.95310.061*0.568 (13)
H12F0.3648−0.05850.90920.061*0.568 (13)
C11B−0.0441 (11)−0.1112 (3)0.8491 (4)0.0373 (18)*0.568 (13)
H11D−0.1557−0.14580.83300.056*0.568 (13)
H11E0.0908−0.11060.81540.056*0.568 (13)
H11F−0.1288−0.07000.84560.056*0.568 (13)
H30.716 (3)0.0747 (12)0.8421 (16)0.031 (8)*
H20.552 (5)0.0249 (10)0.8088 (13)0.032 (8)*
H8−0.110 (4)0.2296 (9)0.5158 (15)0.029 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0192 (3)0.0192 (3)0.0183 (3)−0.0019 (3)−0.0008 (2)−0.0012 (2)
S20.0203 (3)0.0196 (3)0.0173 (3)0.0028 (3)0.0026 (2)0.0030 (2)
S30.0345 (4)0.0281 (4)0.0365 (4)−0.0027 (3)0.0034 (3)−0.0094 (3)
F30.0234 (8)0.0303 (9)0.0310 (9)0.0029 (7)−0.0076 (7)0.0019 (7)
F20.0369 (9)0.0280 (9)0.0314 (9)0.0029 (7)−0.0043 (7)−0.0111 (7)
O30.0211 (9)0.0261 (10)0.0246 (10)0.0004 (8)0.0035 (8)0.0072 (7)
F10.0321 (9)0.0418 (10)0.0367 (9)−0.0197 (8)−0.0074 (7)0.0067 (8)
O40.0350 (11)0.0257 (10)0.0160 (9)0.0040 (8)0.0028 (8)0.0001 (7)
O60.0254 (10)0.0231 (10)0.0365 (11)0.0061 (8)−0.0002 (8)−0.0009 (8)
O10.0286 (10)0.0236 (10)0.0266 (10)0.0011 (8)−0.0002 (8)−0.0065 (8)
O20.0182 (9)0.0322 (11)0.0274 (10)−0.0031 (8)0.0002 (8)−0.0016 (8)
O50.0405 (12)0.0409 (13)0.0332 (11)−0.0095 (10)0.0097 (9)−0.0107 (9)
N10.0244 (12)0.0249 (12)0.0222 (11)−0.0069 (9)−0.0021 (9)0.0078 (9)
N20.0260 (12)0.0224 (12)0.0198 (11)−0.0015 (10)−0.0034 (9)0.0014 (9)
N30.0199 (12)0.0197 (12)0.0261 (12)0.0012 (10)−0.0012 (10)0.0012 (9)
C20.0161 (12)0.0185 (13)0.0210 (13)0.0006 (10)−0.0002 (10)−0.0013 (10)
C60.0161 (12)0.0200 (13)0.0198 (12)0.0024 (10)0.0019 (10)0.0010 (10)
C30.0192 (13)0.0176 (13)0.0166 (12)0.0044 (10)0.0027 (10)0.0023 (9)
C40.0186 (12)0.0142 (12)0.0215 (12)−0.0014 (10)0.0032 (10)−0.0010 (10)
C80.0241 (14)0.0235 (14)0.0230 (14)−0.0021 (11)−0.0027 (11)0.0007 (11)
C70.0339 (15)0.0263 (15)0.0191 (13)−0.0052 (12)0.0005 (11)0.0034 (11)
C50.0165 (12)0.0202 (13)0.0166 (12)0.0013 (10)0.0004 (10)−0.0016 (10)
C10.0193 (13)0.0176 (13)0.0249 (13)−0.0038 (10)0.0017 (10)0.0016 (10)
C90.0430 (19)0.046 (2)0.0406 (18)−0.0100 (15)0.0059 (15)−0.0059 (15)
C100.0355 (19)0.105 (3)0.0318 (18)0.0104 (19)−0.0032 (15)−0.0200 (19)
S4A0.036 (3)0.0231 (16)0.045 (4)0.005 (2)0.013 (2)0.003 (2)
S4B0.034 (2)0.0217 (13)0.0277 (19)0.0071 (15)0.0101 (13)0.0032 (12)
Geometric parameters (Å, °) top
S1—O21.4278 (17)C3—C41.378 (3)
S1—O11.4310 (18)C4—C51.385 (3)
S1—N21.627 (2)C4—H40.9500
S1—C51.751 (2)C7—H60.9900
S2—O41.4258 (18)C7—H50.9900
S2—O31.4361 (18)C1—H10.9500
S2—N31.609 (2)C9—H9A0.9800
S2—C31.779 (2)C9—H9B0.9800
S3—O51.5023 (19)C9—H9C0.9800
S3—C101.748 (3)C10—H10A0.9800
S3—C91.768 (3)C10—H10B0.9800
F3—C81.341 (3)C10—H10C0.9800
F2—C81.336 (3)S4A—C12A1.776 (12)
F1—C81.340 (3)S4A—C11A1.795 (11)
O6—S4A1.492 (10)C11A—H11A0.9800
O6—S4B1.510 (8)C11A—H11B0.9800
N1—C61.364 (3)C11A—H11C0.9800
N1—C71.445 (3)C12A—H12A0.9800
N1—H70.8800C12A—H12B0.9800
N2—C71.457 (3)C12A—H12C0.9800
N2—H80.871 (10)S4B—C12B1.751 (9)
N3—H30.869 (10)S4B—C11B1.794 (8)
N3—H20.866 (10)C12B—H12D0.9800
C2—C11.374 (3)C12B—H12E0.9800
C2—C31.415 (3)C12B—H12F0.9800
C2—C81.508 (3)C11B—H11D0.9800
C6—C51.404 (3)C11B—H11E0.9800
C6—C11.406 (3)C11B—H11F0.9800
O2—S1—O1118.53 (11)N1—C7—N2111.6 (2)
O2—S1—N2108.38 (11)N1—C7—H6109.3
O1—S1—N2107.84 (11)N2—C7—H6109.3
O2—S1—C5110.04 (11)N1—C7—H5109.3
O1—S1—C5108.33 (11)N2—C7—H5109.3
N2—S1—C5102.52 (12)H6—C7—H5108.0
O4—S2—O3118.94 (10)C4—C5—C6120.8 (2)
O4—S2—N3107.98 (12)C4—C5—S1119.82 (19)
O3—S2—N3105.59 (11)C6—C5—S1119.39 (18)
O4—S2—C3108.71 (11)C2—C1—C6121.8 (2)
O3—S2—C3106.67 (11)C2—C1—H1119.1
N3—S2—C3108.57 (11)C6—C1—H1119.1
O5—S3—C10106.85 (14)S3—C9—H9A109.5
O5—S3—C9105.99 (13)S3—C9—H9B109.5
C10—S3—C997.83 (18)H9A—C9—H9B109.5
C6—N1—C7121.9 (2)S3—C9—H9C109.5
C6—N1—H7119.0H9A—C9—H9C109.5
C7—N1—H7119.0H9B—C9—H9C109.5
C7—N2—S1112.16 (17)S3—C10—H10A109.5
C7—N2—H8108.6 (18)S3—C10—H10B109.5
S1—N2—H8110.1 (19)H10A—C10—H10B109.5
S2—N3—H3111.4 (19)S3—C10—H10C109.5
S2—N3—H2113 (2)H10A—C10—H10C109.5
H3—N3—H2117 (3)H10B—C10—H10C109.5
C1—C2—C3120.2 (2)O6—S4A—C12A103.6 (6)
C1—C2—C8116.2 (2)O6—S4A—C11A103.3 (5)
C3—C2—C8123.7 (2)C12A—S4A—C11A97.5 (6)
N1—C6—C5122.4 (2)O6—S4B—C12B108.0 (4)
N1—C6—C1120.4 (2)O6—S4B—C11B105.4 (4)
C5—C6—C1117.3 (2)C12B—S4B—C11B96.7 (5)
C4—C3—C2118.2 (2)S4B—C12B—H12D109.5
C4—C3—S2115.61 (18)S4B—C12B—H12E109.5
C2—C3—S2126.14 (19)H12D—C12B—H12E109.5
C3—C4—C5121.7 (2)S4B—C12B—H12F109.5
C3—C4—H4119.2H12D—C12B—H12F109.5
C5—C4—H4119.2H12E—C12B—H12F109.5
F2—C8—F1106.2 (2)S4B—C11B—H11D109.5
F2—C8—F3107.3 (2)S4B—C11B—H11E109.5
F1—C8—F3105.5 (2)H11D—C11B—H11E109.5
F2—C8—C2112.3 (2)S4B—C11B—H11F109.5
F1—C8—C2112.3 (2)H11D—C11B—H11F109.5
F3—C8—C2112.8 (2)H11E—C11B—H11F109.5
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H2···O50.87 (2)1.98 (2)2.837 (3)170 (2)
N3—H3···O3i0.869 (19)2.383 (17)3.158 (3)149 (2)
N1—H7···O6ii0.882.122.836 (3)139
N2—H8···O6iii0.87 (2)2.03 (2)2.880 (3)166 (2)
Symmetry codes: (i) x+1, y, z; (ii) −x+1, y+1/2, −z+3/2; (iii) −x, y+1/2, −z+3/2.
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N3—H2···O50.87 (2)1.98 (2)2.837 (3)170 (2)
N3—H3···O3i0.869 (19)2.383 (17)3.158 (3)149 (2)
N1—H7···O6ii0.882.122.836 (3)139
N2—H8···O6iii0.87 (2)2.03 (2)2.880 (3)166 (2)
Symmetry codes: (i) x+1, y, z; (ii) −x+1, y+1/2, −z+3/2; (iii) −x, y+1/2, −z+3/2.
Acknowledgements top

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: http://www.cposs.org.uk).

references
References top

Accelrys (2001). Cerius2. Version 4.9. Accelrys Inc., San Diego, California, USA.

Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335–338.

Etter, M. C. (1990). Acc. Chem. Res. 23, 120–126.

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565–?.

Fernandes, P., Shankland, K., Florence, A. J., Shankland, N. & Johnston, A. (2007). J. Pharm. Sci. 96, 1192–1202.

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.

Florence, A. J., Johnston, A., Fernandes, P., Shankland, N. & Shankland, K. (2006). J. Appl. Cryst. 39, 922–924.

Johnston, A., Florence, A. J., Shankland, N., Kennedy, A. R., Shankland, K. & Price, S. L. (2007). Cryst. Growth Des. 7, 705–712.

Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.29.2. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.

Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.

Westrip, S. P. (2007). publCIF. In preparation.