Hydro­flumethia­zide dimethyl sulfoxide disolvate

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).

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.003 Å
• Disorder in solvent or counterion
• R factor = 0.040
• wR factor = 0.097
• Data-to-parameter ratio = 14.7

checkCIF/PLATON results

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Alert level C
PLAT042_ALERT_1_C Calc. and Rep. MoietyFormula Strings Differ ....          ?
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.98
PLAT202_ALERT_3_C Isotropic non-H Atoms in Anion/Solvent .........          2
PLAT302_ALERT_4_C Anion/Solvent Disorder .........................      27.00 Perc.
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              C2 H6 O S

Alert level G
ABSTM02_ALERT_3_G  When printed, the submitted absorption T values will be
            replaced by the scaled T values. Since the ratio of scaled T's
            is identical to the ratio of reported T values, the scaling
            does not imply a change to the absorption corrections used in
            the study.
            Ratio of Tmax expected/reported      0.979
            Tmax scaled      0.979 Tmin scaled      0.897
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          3

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
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   0 ALERT type 5 Informative message, check


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Alert level A
PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: Collaborative project involving two institutions. Three students with different supervisors

   1 ALERT level A = Data missing that is essential or data in wrong format
   0 ALERT level G = General alerts. Data that may be required is missing

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S1. Comment

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

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).

S2. Experimental

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.

S3. Refinement

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

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

	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.
	Fig. 2. The R3^2(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

Crystal data

C8H8F3N3O4S2·2C2H6OS	F(000) = 1008
Mr = 487.55	Dx = 1.609 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 8339 reflections
a = 5.5570 (1) Å	θ = 2.5–28.6°
b = 20.8433 (4) Å	µ = 0.53 mm^−1
c = 17.4142 (3) Å	T = 150 K
β = 93.540 (2)°	Needle, colourless
V = 2013.17 (6) Å^3	0.30 × 0.04 × 0.04 mm
Z = 4

Data collection

Oxford Diffraction Gemini diffractometer	4097 independent reflections
Radiation source: Enhance (Mo) X-ray source	3125 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.039
Detector resolution: 15.9745 pixels mm^-1	θmax = 26.4°, θmin = 2.5°
φ and ω scans	h = −6→6
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	k = −25→26
Tmin = 0.917, Tmax = 1.000	l = −21→21
20791 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: structure-invariant direct methods
R[F^2 > 2σ(F^2)] = 0.040	Hydrogen site location: difference Fourier map
wR(F^2) = 0.097	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0499P)^2 + 0.661P] where P = (Fo^2 + 2Fc^2)/3
4097 reflections	(Δ/σ)max = 0.001
279 parameters	Δρmax = 0.64 e Å^−3
3 restraints	Δρmin = −0.35 e Å^−3

Special details

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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	−0.01352 (11)	0.13727 (3)	0.55321 (3)	0.01901 (15)
S2	0.35866 (11)	0.10571 (3)	0.84249 (3)	0.01901 (15)
S3	0.60374 (14)	−0.07563 (3)	0.67961 (4)	0.03297 (19)
F3	0.8236 (3)	0.18575 (7)	0.84137 (8)	0.0287 (4)
F2	0.5879 (3)	0.26592 (7)	0.85879 (9)	0.0324 (4)
O3	0.1426 (3)	0.06775 (8)	0.83638 (10)	0.0239 (4)
F1	0.8528 (3)	0.27104 (8)	0.77485 (9)	0.0373 (4)
O4	0.4004 (3)	0.14679 (8)	0.90741 (9)	0.0255 (4)
O6	0.2205 (3)	−0.18457 (9)	0.94408 (11)	0.0285 (4)
O1	0.0979 (3)	0.08578 (8)	0.51422 (10)	0.0263 (4)
O2	−0.2453 (3)	0.12674 (9)	0.58203 (10)	0.0260 (4)
O5	0.4708 (4)	−0.05271 (10)	0.74696 (11)	0.0379 (5)
N1	0.3378 (4)	0.24697 (11)	0.54436 (12)	0.0240 (5)
H7	0.4192	0.2829	0.5406	0.036*
N2	−0.0319 (4)	0.19850 (10)	0.49524 (12)	0.0229 (5)
N3	0.5777 (4)	0.05525 (11)	0.84224 (13)	0.0220 (5)
C2	0.5116 (4)	0.20571 (11)	0.74488 (14)	0.0186 (5)
C6	0.3410 (4)	0.21632 (12)	0.61364 (14)	0.0186 (5)
C3	0.3592 (4)	0.15283 (11)	0.75733 (13)	0.0178 (5)
C4	0.1986 (4)	0.13402 (11)	0.69812 (13)	0.0180 (5)
H4	0.0920	0.0994	0.7061	0.027*
C8	0.6924 (5)	0.23187 (13)	0.80502 (14)	0.0237 (6)
C7	0.2046 (5)	0.22208 (13)	0.47697 (14)	0.0265 (6)
H6	0.2971	0.1867	0.4549	0.040*
H5	0.1848	0.2564	0.4378	0.040*
C5	0.1887 (4)	0.16436 (12)	0.62726 (13)	0.0178 (5)
C1	0.4980 (4)	0.23682 (12)	0.67517 (14)	0.0206 (5)
H1	0.5975	0.2732	0.6684	0.031*
C9	0.8253 (6)	−0.01685 (16)	0.66462 (18)	0.0431 (8)
H9A	0.9498	−0.0183	0.7070	0.065*
H9B	0.7502	0.0257	0.6626	0.065*
H9C	0.8989	−0.0254	0.6159	0.065*
C10	0.4173 (6)	−0.0605 (2)	0.59702 (18)	0.0577 (11)
H10A	0.2706	−0.0864	0.5983	0.087*
H10B	0.5028	−0.0717	0.5513	0.087*
H10C	0.3742	−0.0149	0.5952	0.087*
S4A	0.1219 (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	−0.1408	0.8739	0.088*	0.432 (13)
H11B	−0.0009	−0.0932	0.8390	0.088*	0.432 (13)
H11C	−0.1890	−0.0666	0.8974	0.088*	0.432 (13)
C12A	0.3508 (16)	−0.0662 (3)	0.9396 (4)	0.0231 (19)*	0.432 (13)
H12A	0.4946	−0.0726	0.9742	0.035*	0.432 (13)
H12B	0.2929	−0.0221	0.9447	0.035*	0.432 (13)
H12C	0.3913	−0.0738	0.8864	0.035*	0.432 (13)
S4B	0.0685 (12)	−0.1247 (4)	0.9465 (4)	0.0275 (8)	0.568 (13)
C12B	0.2631 (15)	−0.0585 (3)	0.9532 (4)	0.0408 (18)*	0.568 (13)
H12D	0.3652	−0.0613	1.0010	0.061*	0.568 (13)
H12E	0.1683	−0.0189	0.9531	0.061*	0.568 (13)
H12F	0.3648	−0.0585	0.9092	0.061*	0.568 (13)
C11B	−0.0441 (11)	−0.1112 (3)	0.8491 (4)	0.0373 (18)*	0.568 (13)
H11D	−0.1557	−0.1458	0.8330	0.056*	0.568 (13)
H11E	0.0908	−0.1106	0.8154	0.056*	0.568 (13)
H11F	−0.1288	−0.0700	0.8456	0.056*	0.568 (13)
H3	0.716 (3)	0.0747 (12)	0.8421 (16)	0.031 (8)*
H2	0.552 (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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0192 (3)	0.0192 (3)	0.0183 (3)	−0.0019 (3)	−0.0008 (2)	−0.0012 (2)
S2	0.0203 (3)	0.0196 (3)	0.0173 (3)	0.0028 (3)	0.0026 (2)	0.0030 (2)
S3	0.0345 (4)	0.0281 (4)	0.0365 (4)	−0.0027 (3)	0.0034 (3)	−0.0094 (3)
F3	0.0234 (8)	0.0303 (9)	0.0310 (9)	0.0029 (7)	−0.0076 (7)	0.0019 (7)
F2	0.0369 (9)	0.0280 (9)	0.0314 (9)	0.0029 (7)	−0.0043 (7)	−0.0111 (7)
O3	0.0211 (9)	0.0261 (10)	0.0246 (10)	0.0004 (8)	0.0035 (8)	0.0072 (7)
F1	0.0321 (9)	0.0418 (10)	0.0367 (9)	−0.0197 (8)	−0.0074 (7)	0.0067 (8)
O4	0.0350 (11)	0.0257 (10)	0.0160 (9)	0.0040 (8)	0.0028 (8)	0.0001 (7)
O6	0.0254 (10)	0.0231 (10)	0.0365 (11)	0.0061 (8)	−0.0002 (8)	−0.0009 (8)
O1	0.0286 (10)	0.0236 (10)	0.0266 (10)	0.0011 (8)	−0.0002 (8)	−0.0065 (8)
O2	0.0182 (9)	0.0322 (11)	0.0274 (10)	−0.0031 (8)	0.0002 (8)	−0.0016 (8)
O5	0.0405 (12)	0.0409 (13)	0.0332 (11)	−0.0095 (10)	0.0097 (9)	−0.0107 (9)
N1	0.0244 (12)	0.0249 (12)	0.0222 (11)	−0.0069 (9)	−0.0021 (9)	0.0078 (9)
N2	0.0260 (12)	0.0224 (12)	0.0198 (11)	−0.0015 (10)	−0.0034 (9)	0.0014 (9)
N3	0.0199 (12)	0.0197 (12)	0.0261 (12)	0.0012 (10)	−0.0012 (10)	0.0012 (9)
C2	0.0161 (12)	0.0185 (13)	0.0210 (13)	0.0006 (10)	−0.0002 (10)	−0.0013 (10)
C6	0.0161 (12)	0.0200 (13)	0.0198 (12)	0.0024 (10)	0.0019 (10)	0.0010 (10)
C3	0.0192 (13)	0.0176 (13)	0.0166 (12)	0.0044 (10)	0.0027 (10)	0.0023 (9)
C4	0.0186 (12)	0.0142 (12)	0.0215 (12)	−0.0014 (10)	0.0032 (10)	−0.0010 (10)
C8	0.0241 (14)	0.0235 (14)	0.0230 (14)	−0.0021 (11)	−0.0027 (11)	0.0007 (11)
C7	0.0339 (15)	0.0263 (15)	0.0191 (13)	−0.0052 (12)	0.0005 (11)	0.0034 (11)
C5	0.0165 (12)	0.0202 (13)	0.0166 (12)	0.0013 (10)	0.0004 (10)	−0.0016 (10)
C1	0.0193 (13)	0.0176 (13)	0.0249 (13)	−0.0038 (10)	0.0017 (10)	0.0016 (10)
C9	0.0430 (19)	0.046 (2)	0.0406 (18)	−0.0100 (15)	0.0059 (15)	−0.0059 (15)
C10	0.0355 (19)	0.105 (3)	0.0318 (18)	0.0104 (19)	−0.0032 (15)	−0.0200 (19)
S4A	0.036 (3)	0.0231 (16)	0.045 (4)	0.005 (2)	0.013 (2)	0.003 (2)
S4B	0.034 (2)	0.0217 (13)	0.0277 (19)	0.0071 (15)	0.0101 (13)	0.0032 (12)

Geometric parameters (Å, º)

S1—O2	1.4278 (17)	C3—C4	1.378 (3)
S1—O1	1.4310 (18)	C4—C5	1.385 (3)
S1—N2	1.627 (2)	C4—H4	0.9500
S1—C5	1.751 (2)	C7—H6	0.9900
S2—O4	1.4258 (18)	C7—H5	0.9900
S2—O3	1.4361 (18)	C1—H1	0.9500
S2—N3	1.609 (2)	C9—H9A	0.9800
S2—C3	1.779 (2)	C9—H9B	0.9800
S3—O5	1.5023 (19)	C9—H9C	0.9800
S3—C10	1.748 (3)	C10—H10A	0.9800
S3—C9	1.768 (3)	C10—H10B	0.9800
F3—C8	1.341 (3)	C10—H10C	0.9800
F2—C8	1.336 (3)	S4A—C12A	1.776 (12)
F1—C8	1.340 (3)	S4A—C11A	1.795 (11)
O6—S4A	1.492 (10)	C11A—H11A	0.9800
O6—S4B	1.510 (8)	C11A—H11B	0.9800
N1—C6	1.364 (3)	C11A—H11C	0.9800
N1—C7	1.445 (3)	C12A—H12A	0.9800
N1—H7	0.8800	C12A—H12B	0.9800
N2—C7	1.457 (3)	C12A—H12C	0.9800
N2—H8	0.871 (10)	S4B—C12B	1.751 (9)
N3—H3	0.869 (10)	S4B—C11B	1.794 (8)
N3—H2	0.866 (10)	C12B—H12D	0.9800
C2—C1	1.374 (3)	C12B—H12E	0.9800
C2—C3	1.415 (3)	C12B—H12F	0.9800
C2—C8	1.508 (3)	C11B—H11D	0.9800
C6—C5	1.404 (3)	C11B—H11E	0.9800
C6—C1	1.406 (3)	C11B—H11F	0.9800
O2—S1—O1	118.53 (11)	N1—C7—N2	111.6 (2)
O2—S1—N2	108.38 (11)	N1—C7—H6	109.3
O1—S1—N2	107.84 (11)	N2—C7—H6	109.3
O2—S1—C5	110.04 (11)	N1—C7—H5	109.3
O1—S1—C5	108.33 (11)	N2—C7—H5	109.3
N2—S1—C5	102.52 (12)	H6—C7—H5	108.0
O4—S2—O3	118.94 (10)	C4—C5—C6	120.8 (2)
O4—S2—N3	107.98 (12)	C4—C5—S1	119.82 (19)
O3—S2—N3	105.59 (11)	C6—C5—S1	119.39 (18)
O4—S2—C3	108.71 (11)	C2—C1—C6	121.8 (2)
O3—S2—C3	106.67 (11)	C2—C1—H1	119.1
N3—S2—C3	108.57 (11)	C6—C1—H1	119.1
O5—S3—C10	106.85 (14)	S3—C9—H9A	109.5
O5—S3—C9	105.99 (13)	S3—C9—H9B	109.5
C10—S3—C9	97.83 (18)	H9A—C9—H9B	109.5
C6—N1—C7	121.9 (2)	S3—C9—H9C	109.5
C6—N1—H7	119.0	H9A—C9—H9C	109.5
C7—N1—H7	119.0	H9B—C9—H9C	109.5
C7—N2—S1	112.16 (17)	S3—C10—H10A	109.5
C7—N2—H8	108.6 (18)	S3—C10—H10B	109.5
S1—N2—H8	110.1 (19)	H10A—C10—H10B	109.5
S2—N3—H3	111.4 (19)	S3—C10—H10C	109.5
S2—N3—H2	113 (2)	H10A—C10—H10C	109.5
H3—N3—H2	117 (3)	H10B—C10—H10C	109.5
C1—C2—C3	120.2 (2)	O6—S4A—C12A	103.6 (6)
C1—C2—C8	116.2 (2)	O6—S4A—C11A	103.3 (5)
C3—C2—C8	123.7 (2)	C12A—S4A—C11A	97.5 (6)
N1—C6—C5	122.4 (2)	O6—S4B—C12B	108.0 (4)
N1—C6—C1	120.4 (2)	O6—S4B—C11B	105.4 (4)
C5—C6—C1	117.3 (2)	C12B—S4B—C11B	96.7 (5)
C4—C3—C2	118.2 (2)	S4B—C12B—H12D	109.5
C4—C3—S2	115.61 (18)	S4B—C12B—H12E	109.5
C2—C3—S2	126.14 (19)	H12D—C12B—H12E	109.5
C3—C4—C5	121.7 (2)	S4B—C12B—H12F	109.5
C3—C4—H4	119.2	H12D—C12B—H12F	109.5
C5—C4—H4	119.2	H12E—C12B—H12F	109.5
F2—C8—F1	106.2 (2)	S4B—C11B—H11D	109.5
F2—C8—F3	107.3 (2)	S4B—C11B—H11E	109.5
F1—C8—F3	105.5 (2)	H11D—C11B—H11E	109.5
F2—C8—C2	112.3 (2)	S4B—C11B—H11F	109.5
F1—C8—C2	112.3 (2)	H11D—C11B—H11F	109.5
F3—C8—C2	112.8 (2)	H11E—C11B—H11F	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H2···O5	0.87 (2)	1.98 (2)	2.837 (3)	170 (2)
N3—H3···O3^i	0.87 (2)	2.38 (2)	3.158 (3)	149 (2)
N1—H7···O6^ii	0.88	2.12	2.836 (3)	139
N2—H8···O6^iii	0.87 (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.