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Hydro­chloro­thia­zide di­methyl sulfoxide solvate

aDepartment of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, and bWestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland
*Correspondence e-mail: alastair.florence@strath.ac.uk

(Received 23 March 2006; accepted 6 May 2006; online 12 May 2006)

Hydro­chloro­thia­zide forms a 1:1 solvate with dimethyl sulfoxide, C7H8ClN3O4S2·C2H6OS. The crystal structure contains a hydrogen-bonding network comprising three N—H⋯O contacts.

Comment

Hydro­chloro­thia­zide (HCT) is a thia­zide diuretic which is known to crystallize in at least two non-solvated forms; form I (Dupont & Dideberg, 1972[Dupont, L. & Dideberg, O. (1972). Acta Cryst. B28, 2340-2347.]) and form II (Florence et al., 2005[Florence, A. J., Johnston, A., Fernandes, P., Shankland, K., Stevens, H. N. E., Osmundsen, S. & Mullen, A. B. (2005). Acta Cryst. E61, o2798-o2800.]). The dimethyl sulfoxide (DMSO) solvate, (I)[link], was produced during an automated parallel crystallization polymorph search on HCT. The sample was identified as a new form using multi-sample X-ray powder diffraction analysis of all recrystallized samples (Florence et al., 2003[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.]). Subsequent manual recrystallization by slow evaporation of a saturated DMSO solution at 278 K yielded samples of (I)[link] suitable for single-crystal X-ray analysis (Fig. 1[link]).

[Scheme 1]

In (I)[link], the six-membered ring N1—S1—C3—C2—N2—C1 in HCT displays a puckered conformation, atom N1 having a deviation of 0.622 (2) Å from the least-squares plane through atoms C2–C7. The sulfonamide side chain adopts an N3—S2—C5—C6 torsion angle of −62.0 (2)°, such that O3 eclipses H4, and atoms O4 and N3 are staggered with respect to Cl1.

The crystal structure is stabilized by three N—H⋯O hydrogen bonds inter­connecting (a) HCT mol­ecules (Fig. 2[link], contact 1) and forming an R22(8) (Etter, 1990[Etter, M. C. (1990). Acc. Chem. Res. 23, 120-126.]) centrosymmetric dimer (Fig. 3[link]), and (b) HCT and two DMSO mol­ecules (Fig. 2[link], contacts 2 and 3).

The aromatic ring formed by atoms C2–C7 is involved in two offset face-to-face ππ inter­actions between nearest-neighbour HCT mol­ecules with centroid–centroid distances/perpendicular distances between the corresponding planes equal to 4.354 (2)/3.58 Å (centroid at −x, 1 − y, 2 − z) and 4.466 (2)/3.57 Å (centroid at 1 − x, 1 − y, 2 − z). The HCT aromatic rings form a stacked arrangement in the direction of the a axis. The structure also contains three C—H⋯O contacts between HCT and HCT (Fig.2, contact 4) and between HCT and DMSO (contacts 5 and 6).

[Figure 1]
Figure 1
Plot of the asymmetric-unit contents with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
Figure 2
Intermolecular interactions in (I)[link]. Dashed lines indicate hydrogen bonds and unique contacts are labelled as follows: 1 = N3⋯O4, 3.004 (3)Å, O4 in the mol­ecule at (−x, 2 − y, 2 − z); 2 = N2⋯O5, 2.806 (3)Å, O5 in the mol­ecule at (1 − x, 1 − y, 2 − z); 3 = N3⋯O5, 2.776 (3)Å; O5 in the mol­ecule at (−1 + x, y, z); 4 = C1⋯O4, 3.347 (3)Å, O4 in the mol­ecule at (x, −1 + y, z); 5 = C7⋯O5, 3.289 (3)Å, O5 in the mol­ecule at (1 − x, 1 − y, 2 − z); 6 = C8⋯O3, 3.228 (4)Å, O3 in the mol­ecule at (1 − x, 2 − y, 1 − z). Contacts calculated and illustrated using PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]; program version 150306)
[Figure 3]
Figure 3
The R22(8) hydrogen-bonded motif in the crystal structure of (I)[link].

Experimental

A single-crystal sample of the title compound was recrystallized by slow evaporation of a dimethyl sulfoxide solution at 278 K.

Crystal data
  • C7H8ClN3O4S2·C2H6OS

  • Mr = 375.86

  • Triclinic, [P \overline 1]

  • a = 7.5068 (4) Å

  • b = 9.8272 (5) Å

  • c = 10.7311 (6) Å

  • α = 85.639 (3)°

  • β = 73.896 (3)°

  • γ = 80.246 (3)°

  • V = 749.23 (7) Å3

  • Z = 2

  • Dx = 1.666 Mg m−3

  • Mo Kα radiation

  • μ = 0.70 mm−1

  • T = 123 (2) K

  • Cut fragment, colourless

  • 0.28 × 0.28 × 0.10 mm

Data collection
  • Nonius KappaCCD diffractometer

  • φ and ω scans

  • Absorption correction: none

  • 10594 measured reflections

  • 3267 independent reflections

  • 2669 reflections with I > 2σ(I)

  • Rint = 0.055

  • θmax = 27.2°

Refinement
  • Refinement on F2

  • R[F2 > 2σ(F2)] = 0.040

  • wR(F2) = 0.110

  • S = 1.03

  • 3267 reflections

  • 208 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • w = 1/[σ2(Fo2) + (0.0592P)2 + 0.534P] where P = (Fo2 + 2Fc2)/3

  • (Δ/σ)max = 0.001

  • Δρmax = 0.47 e Å−3

  • Δρmin = −0.48 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N3—H4N⋯O4i 0.80 (3) 2.27 (3) 3.004 (3) 153 (3)
N2—H2N⋯O5ii 0.81 (3) 2.02 (3) 2.806 (3) 164 (3)
N3—H3N⋯O5iii 0.83 (3) 1.95 (3) 2.776 (3) 172 (3)
C1—H1A⋯O4iv 0.99 2.46 3.347 (3) 149
C7—H7⋯O5ii 0.95 2.56 3.289 (3) 134
C8—H8B⋯O3v 0.98 2.53 3.228 (4) 128
Symmetry codes: (i) -x, -y+2, -z+2; (ii) -x+1, -y+1, -z+2; (iii) x-1, y, z; (iv) x, y-1, z; (v) -x+1, -y+2, -z+1.

H atoms bonded to N atoms were found in difference maps and refined isotropically, but all other H atoms were constrained to idealized geometry using a riding model; Uiso(H) = 1.2Ueq(C) and C—H = 0.95 (CH group) or 0.99 Å (CH2 groups).

Data collection: COLLECT (Hooft, 1988[Hooft, R. (1988). COLLECT. Nonius BV, Delft, The Netherlands.]) and DENZO (Otwin­owski & Minor, 1997[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.]); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]); molecular graphics: PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]); software used to prepare material for publication: SHELXL97.

Supporting information


Computing details top

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.

Hydrochlorothiazide dimethyl sulfoxide solvate top
Crystal data top
C7H8ClN3O4S2·C2H6OSZ = 2
Mr = 375.86F(000) = 388
Triclinic, P1Dx = 1.666 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.5068 (4) ÅCell parameters from 2971 reflections
b = 9.8272 (5) Åθ = 2.9–27.1°
c = 10.7311 (6) ŵ = 0.70 mm1
α = 85.639 (3)°T = 123 K
β = 73.896 (3)°Cut fragment, colourless
γ = 80.246 (3)°0.28 × 0.28 × 0.10 mm
V = 749.23 (7) Å3
Data collection top
Nonius KappaCCD
diffractometer
2669 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.055
Graphite monochromatorθmax = 27.2°, θmin = 2.9°
φ and ω scansh = 99
10594 measured reflectionsk = 1112
3267 independent reflectionsl = 1313
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.0592P)2 + 0.534P]
where P = (Fo2 + 2Fc2)/3
3267 reflections(Δ/σ)max = 0.001
208 parametersΔρmax = 0.47 e Å3
0 restraintsΔρmin = 0.48 e Å3
Special details top

Experimental. Although no formal absorption correction was applied, the standard Kappa CCD methodology involves collecting a large number of redundant reflections and processing via SCALEPACK. This effectively introduces a multi-scan type correction suitable for weakly absorbing molecules.

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 (Å2) top
xyzUiso*/Ueq
Cl10.02575 (8)0.73342 (6)1.11711 (6)0.02319 (16)
S10.51163 (9)0.34312 (6)0.67153 (6)0.02145 (16)
S20.15774 (9)0.85850 (6)0.81869 (6)0.02141 (16)
S30.69526 (9)0.76246 (6)0.63385 (6)0.02243 (17)
O10.6400 (3)0.41391 (19)0.57579 (18)0.0319 (4)
O20.3873 (3)0.27152 (19)0.63320 (18)0.0300 (4)
O30.2162 (3)0.86589 (18)0.67974 (17)0.0295 (4)
O40.2406 (3)0.93652 (17)0.89048 (18)0.0267 (4)
O50.7163 (3)0.7637 (2)0.77073 (17)0.0322 (4)
N10.6358 (3)0.2308 (2)0.7473 (2)0.0245 (5)
N20.4255 (3)0.2776 (2)0.9606 (2)0.0225 (5)
N30.0632 (3)0.9093 (2)0.8633 (2)0.0248 (5)
C10.5231 (4)0.1724 (2)0.8661 (2)0.0236 (5)
H1A0.42990.12470.84460.028*
H1B0.60560.10300.90500.028*
C20.3507 (3)0.4058 (2)0.9263 (2)0.0182 (5)
C30.3807 (3)0.4550 (2)0.7960 (2)0.0181 (5)
C40.3152 (3)0.5911 (2)0.7652 (2)0.0190 (5)
H40.34150.62240.67700.023*
C50.2114 (3)0.6819 (2)0.8622 (2)0.0179 (5)
C60.1710 (3)0.6301 (2)0.9914 (2)0.0192 (5)
C70.2385 (3)0.4977 (2)1.0242 (2)0.0193 (5)
H70.21030.46711.11270.023*
C80.6947 (6)0.9341 (3)0.5754 (3)0.0489 (9)
H8A0.57870.99110.62230.073*
H8B0.70230.93840.48260.073*
H8C0.80290.96870.58880.073*
C90.9207 (5)0.6894 (4)0.5400 (3)0.0517 (10)
H9A1.01420.74400.54850.078*
H9B0.92060.68940.44870.078*
H9C0.95180.59420.57100.078*
H1N0.729 (5)0.264 (3)0.758 (3)0.036 (9)*
H2N0.407 (4)0.261 (3)1.038 (3)0.023 (7)*
H3N0.131 (4)0.872 (3)0.831 (3)0.023 (8)*
H4N0.107 (4)0.923 (3)0.939 (3)0.026 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0229 (3)0.0246 (3)0.0208 (3)0.0002 (2)0.0042 (2)0.0075 (2)
S10.0253 (3)0.0181 (3)0.0191 (3)0.0034 (2)0.0060 (2)0.0041 (2)
S20.0236 (3)0.0151 (3)0.0238 (3)0.0000 (2)0.0048 (2)0.0020 (2)
S30.0241 (3)0.0226 (3)0.0207 (3)0.0030 (2)0.0065 (2)0.0015 (2)
O10.0332 (11)0.0284 (10)0.0257 (10)0.0020 (8)0.0022 (8)0.0011 (8)
O20.0321 (10)0.0292 (10)0.0316 (10)0.0003 (8)0.0132 (8)0.0109 (8)
O30.0374 (11)0.0212 (9)0.0238 (10)0.0024 (8)0.0035 (8)0.0026 (7)
O40.0271 (10)0.0185 (8)0.0346 (10)0.0042 (7)0.0066 (8)0.0057 (7)
O50.0353 (11)0.0433 (11)0.0196 (9)0.0103 (9)0.0088 (8)0.0038 (8)
N10.0244 (11)0.0207 (10)0.0276 (12)0.0008 (9)0.0076 (9)0.0026 (9)
N20.0292 (12)0.0183 (10)0.0194 (11)0.0009 (8)0.0075 (9)0.0001 (8)
N30.0245 (12)0.0245 (11)0.0262 (13)0.0015 (9)0.0100 (10)0.0064 (9)
C10.0305 (14)0.0148 (11)0.0252 (13)0.0007 (10)0.0089 (11)0.0001 (9)
C20.0172 (11)0.0178 (11)0.0214 (12)0.0040 (9)0.0068 (9)0.0022 (9)
C30.0195 (11)0.0159 (11)0.0189 (12)0.0012 (9)0.0058 (9)0.0024 (9)
C40.0196 (12)0.0189 (11)0.0177 (11)0.0017 (9)0.0045 (9)0.0012 (9)
C50.0184 (11)0.0156 (11)0.0189 (11)0.0015 (9)0.0042 (9)0.0019 (9)
C60.0168 (11)0.0211 (11)0.0209 (12)0.0047 (9)0.0043 (9)0.0064 (9)
C70.0208 (12)0.0203 (11)0.0173 (11)0.0047 (9)0.0048 (9)0.0014 (9)
C80.086 (3)0.0267 (15)0.0400 (18)0.0107 (16)0.0281 (18)0.0061 (13)
C90.0374 (18)0.072 (2)0.0395 (19)0.0171 (17)0.0091 (15)0.0262 (17)
Geometric parameters (Å, º) top
Cl1—C61.749 (2)N3—H4N0.80 (3)
S1—O21.4195 (19)C1—H1A0.9900
S1—O11.427 (2)C1—H1B0.9900
S1—N11.638 (2)C2—C31.413 (3)
S1—C31.758 (2)C2—C71.422 (3)
S2—O31.4327 (19)C3—C41.393 (3)
S2—O41.4443 (19)C4—C51.394 (3)
S2—N31.595 (2)C4—H40.9500
S2—C51.771 (2)C5—C61.409 (3)
S3—O51.5213 (18)C6—C71.371 (3)
S3—C81.754 (3)C7—H70.9500
S3—C91.774 (3)C8—H8A0.9800
N1—C11.458 (3)C8—H8B0.9800
N1—H1N0.85 (3)C8—H8C0.9800
N2—C21.358 (3)C9—H9A0.9800
N2—C11.457 (3)C9—H9B0.9800
N2—H2N0.81 (3)C9—H9C0.9800
N3—H3N0.83 (3)
O2—S1—O1119.64 (12)N2—C2—C3123.0 (2)
O2—S1—N1107.28 (12)N2—C2—C7119.7 (2)
O1—S1—N1107.26 (12)C3—C2—C7117.3 (2)
O2—S1—C3108.77 (11)C4—C3—C2121.4 (2)
O1—S1—C3110.26 (11)C4—C3—S1119.71 (18)
N1—S1—C3102.16 (11)C2—C3—S1118.87 (17)
O3—S2—O4118.94 (12)C3—C4—C5120.8 (2)
O3—S2—N3107.80 (13)C3—C4—H4119.6
O4—S2—N3106.60 (12)C5—C4—H4119.6
O3—S2—C5105.53 (11)C4—C5—C6117.7 (2)
O4—S2—C5107.25 (11)C4—C5—S2118.49 (18)
N3—S2—C5110.66 (12)C6—C5—S2123.52 (17)
O5—S3—C8105.16 (14)C7—C6—C5122.4 (2)
O5—S3—C9104.42 (14)C7—C6—Cl1117.17 (19)
C8—S3—C999.1 (2)C5—C6—Cl1120.43 (18)
C1—N1—S1113.31 (18)C6—C7—C2120.2 (2)
C1—N1—H1N113 (2)C6—C7—H7119.9
S1—N1—H1N111 (2)C2—C7—H7119.9
C2—N2—C1122.8 (2)S3—C8—H8A109.5
C2—N2—H2N116 (2)S3—C8—H8B109.5
C1—N2—H2N121 (2)H8A—C8—H8B109.5
S2—N3—H3N118 (2)S3—C8—H8C109.5
S2—N3—H4N116 (2)H8A—C8—H8C109.5
H3N—N3—H4N113 (3)H8B—C8—H8C109.5
N2—C1—N1112.2 (2)S3—C9—H9A109.5
N2—C1—H1A109.2S3—C9—H9B109.5
N1—C1—H1A109.2H9A—C9—H9B109.5
N2—C1—H1B109.2S3—C9—H9C109.5
N1—C1—H1B109.2H9A—C9—H9C109.5
H1A—C1—H1B107.9H9B—C9—H9C109.5
O2—S1—N1—C163.1 (2)S1—C3—C4—C5179.87 (18)
O1—S1—N1—C1167.15 (17)C3—C4—C5—C61.8 (4)
C3—S1—N1—C151.2 (2)C3—C4—C5—S2172.14 (19)
C2—N2—C1—N137.5 (3)O3—S2—C5—C48.1 (2)
S1—N1—C1—N261.1 (3)O4—S2—C5—C4119.65 (19)
C1—N2—C2—C38.2 (4)N3—S2—C5—C4124.5 (2)
C1—N2—C2—C7172.6 (2)O3—S2—C5—C6178.3 (2)
N2—C2—C3—C4174.4 (2)O4—S2—C5—C653.9 (2)
C7—C2—C3—C44.7 (3)N3—S2—C5—C662.0 (2)
N2—C2—C3—S13.1 (3)C4—C5—C6—C73.7 (4)
C7—C2—C3—S1177.79 (17)S2—C5—C6—C7169.91 (19)
O2—S1—C3—C492.3 (2)C4—C5—C6—Cl1174.82 (18)
O1—S1—C3—C440.7 (2)S2—C5—C6—Cl111.6 (3)
N1—S1—C3—C4154.5 (2)C5—C6—C7—C21.3 (4)
O2—S1—C3—C290.2 (2)Cl1—C6—C7—C2177.25 (18)
O1—S1—C3—C2136.8 (2)N2—C2—C7—C6176.3 (2)
N1—S1—C3—C223.0 (2)C3—C2—C7—C62.9 (3)
C2—C3—C4—C52.4 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H4N···O4i0.80 (3)2.27 (3)3.004 (3)153 (3)
N2—H2N···O5ii0.81 (3)2.02 (3)2.806 (3)164 (3)
N3—H3N···O5iii0.83 (3)1.95 (3)2.776 (3)172 (3)
C1—H1A···O4iv0.992.463.347 (3)149
C7—H7···O5ii0.952.563.289 (3)134
C8—H8B···O3v0.982.533.228 (4)128
Symmetry codes: (i) x, y+2, z+2; (ii) x+1, y+1, z+2; (iii) x1, y, z; (iv) x, y1, z; (v) x+1, y+2, z+1.
 

Acknowledgements

We 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).

References

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