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Acta Cryst. (2007). E63, o4021    [ doi:10.1107/S1600536807042845 ]

Chlorothiazide formic acid solvate (1/2)

A. Johnston, A. J. Florence and A. R. Kennedy

Abstract top

Chlorothiazide forms a 1:2 solvate with formic acid (systematic name: 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide methanoic acid disolvate), C7H6ClN3O4S2·2CH2O2. The compound crystallizes with one chlorothiazide molecule and two solvent molecules in the asymmetric unit and displays an extensive hydrogen-bonding network.

Comment top

Chlorothiazide (CT) is a thiazide diuretic drug that is known to crystallize in at least one non-solvated form (Dupont & Dideberg, 1970; Shankland et al., 1997). The title compound was produced as part of an automated parallel crystallization study (Florence et al., 2006) of CT as part of a wider investigation that couples automated parallel crystallization with crystal structure prediction to investigate the basic science underlying the solid-state diversity of CT and the related thiazide diuretic, hydrochlorothiazide (Johnston 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 formic acid solution by slow evaporation at 278 K yielded a sample suitable for single-crystal x-ray diffraction (Fig. 1).

The molecules crystallize in space group (P21/c) with one chlorothiazide (CT) and two solvent molecules in the asymmetric unit. The structure contains one N—H···N contact between CT molecules that forms an infinite chain of CT extending in the [101] direction. Molecules of CT also stack in the direction of the c axis with a further two N—H···O contacts between CT and each solvent molecule (residues B and C). In addition, two O—H···O interactions connect residue C with residues A and B (Table 1).

The contacts combine to form a layered structure (Fig. 2) comprising alternating layes of CT molecules (residue A) and solvent molecules (residues B and C) in the [010] direction.

Related literature top

For details on experimental methods used to obtain this form, see: Florence et al. (2003, 2006). For previous studies on the anhydrous form of the title compound, see: Dupont & Dideberg (1970); Shankland et al. (1997); for solvated forms, see: Johnston et al. (2007a,b). Intermolecular interactions in polymorphs and solvates of the related thiazide diuretic hydrochlorothiazide have also been studied (Johnston et al., 2007).

Experimental top

A single-crystal sample of the title compound was recrystallized from a saturated formic acid solution by isothermal solvent evaporation at 278 oK.

Refinement top

The H-atoms attached to O or N-atoms were located by difference synthesis and refined isotropically. All other H-atoms were constrained to idealized geometries using a riding model with Uiso(H)=1.2Ueq(C) and C—H=0.95 Å.

Computing details top

Data collection: COLLECT (Hooft, 1988) and DENZO (Otwinowski & Minor, 1997); cell refinement: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1988); data reduction: DENZO (Otwinowski & Minor, 1997); 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: PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. Molecular structure of title compound, showing 50% probablility displacement ellipsoids.
[Figure 2] Fig. 2. Crystal packing of the title compound, viewed down the a-axis. Residues A, B and C (Fig. 1) are coloured red, blue and green, respectively. Hydrogen bonds are shown as grey dashed lines.
6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide methanoic acid disolvate top
Crystal data top
C7H6ClN3O4S2·2CH2O2F(000) = 792
Mr = 387.77Dx = 1.789 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 8.2985 (5) ÅCell parameters from 2389 reflections
b = 21.5271 (14) Åθ = 1.0–27.5°
c = 8.3676 (5) ŵ = 0.60 mm−1
β = 105.580 (3)°T = 123 K
V = 1439.89 (15) Å3Block, colourless
Z = 40.30 × 0.12 × 0.10 mm
Data collection top
Nonius KappaCCD
diffractometer		1872 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.079
graphiteθmax = 26.0°, θmin = 1.9°
phi and ω scansh = −10→10
8698 measured reflectionsk = −26→26
2650 independent reflectionsl = −10→10
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.052 w = 1/[σ2(Fo2) + (0.0295P)2 + 2.9523P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.114(Δ/σ)max = 0.002
S = 1.07Δρmax = 0.49 e Å−3
2650 reflectionsΔρmin = −0.53 e Å−3
228 parameters
Crystal data top
C7H6ClN3O4S2·2CH2O2V = 1439.89 (15) Å3
Mr = 387.77Z = 4
Monoclinic, P21/cMo Kα radiation
a = 8.2985 (5) ŵ = 0.60 mm−1
b = 21.5271 (14) ÅT = 123 K
c = 8.3676 (5) Å0.30 × 0.12 × 0.10 mm
β = 105.580 (3)°
Data collection top
Nonius KappaCCD
diffractometer		1872 reflections with I > 2σ(I)
8698 measured reflectionsRint = 0.079
2650 independent reflectionsθmax = 26.0°
Refinement top
R[F2 > 2σ(F2)] = 0.052H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.114Δρmax = 0.49 e Å−3
S = 1.07Δρmin = −0.53 e Å−3
2650 reflectionsAbsolute structure: ?
228 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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 > 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
Cl10.58237 (12)0.27340 (4)0.40275 (12)0.0165 (3)
S11.15604 (12)0.13926 (4)0.92688 (12)0.0142 (3)
S20.57857 (12)0.12000 (4)0.43857 (12)0.0132 (3)
O11.2736 (3)0.11880 (14)0.8414 (4)0.0241 (7)
O21.0919 (4)0.09369 (13)1.0152 (4)0.0231 (7)
O30.6350 (3)0.05729 (12)0.4813 (3)0.0160 (7)
O40.4262 (3)0.14023 (13)0.4706 (3)0.0188 (7)
O50.9981 (4)0.00567 (13)1.2892 (4)0.0218 (7)
O61.0024 (4)0.10413 (12)1.3725 (4)0.0227 (7)
O70.7176 (4)0.03970 (14)1.0859 (4)0.0232 (7)
O80.5671 (5)0.04283 (17)0.8172 (5)0.0418 (10)
N11.2463 (4)0.19341 (15)1.0552 (4)0.0154 (8)
N21.1002 (4)0.27635 (16)0.8923 (4)0.0137 (7)
N30.5668 (5)0.13232 (18)0.2500 (4)0.0165 (8)
C11.2150 (5)0.25210 (19)1.0209 (5)0.0142 (9)
H11.28170.28101.09630.017*
C20.9839 (5)0.24083 (17)0.7773 (5)0.0124 (9)
C30.8579 (5)0.27031 (17)0.6553 (5)0.0125 (9)
H30.85500.31430.64620.015*
C40.7382 (5)0.23454 (17)0.5490 (5)0.0113 (8)
C50.7398 (5)0.16901 (18)0.5576 (5)0.0122 (8)
C60.8692 (5)0.14063 (18)0.6763 (5)0.0128 (8)
H60.87440.09660.68370.015*
C70.9906 (5)0.17624 (17)0.7838 (5)0.0126 (9)
C81.0677 (5)0.05427 (18)1.3764 (5)0.0187 (10)
H81.17740.04951.44750.022*
C90.7036 (5)0.03154 (18)0.9384 (5)0.0173 (9)
H90.79830.01580.90810.021*
H1H0.898 (7)0.018 (3)1.210 (7)0.058 (18)*
H2H0.562 (6)0.036 (2)0.686 (7)0.045 (15)*
H1N1.086 (6)0.317 (2)0.887 (6)0.040 (15)*
H2N0.470 (6)0.155 (2)0.197 (6)0.032 (13)*
H3N0.608 (6)0.108 (2)0.209 (6)0.034 (17)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0158 (5)0.0160 (5)0.0156 (5)0.0048 (4)0.0004 (4)0.0034 (4)
S10.0124 (5)0.0133 (5)0.0146 (6)0.0017 (4)−0.0005 (4)0.0012 (4)
S20.0125 (5)0.0133 (5)0.0130 (5)0.0001 (4)0.0019 (4)−0.0009 (4)
O10.0166 (16)0.0281 (17)0.0267 (18)0.0082 (13)0.0041 (13)−0.0070 (14)
O20.0241 (17)0.0187 (15)0.0228 (17)−0.0064 (13)−0.0001 (14)0.0077 (13)
O30.0177 (16)0.0113 (14)0.0173 (15)−0.0035 (12)0.0015 (12)0.0002 (11)
O40.0122 (15)0.0221 (15)0.0225 (17)0.0012 (12)0.0053 (13)−0.0026 (12)
O50.0236 (17)0.0136 (15)0.0238 (18)0.0023 (13)−0.0012 (14)−0.0027 (13)
O60.0251 (17)0.0120 (15)0.0317 (19)0.0034 (13)0.0089 (14)0.0009 (13)
O70.0238 (17)0.0293 (17)0.0147 (17)0.0054 (14)0.0020 (13)−0.0046 (13)
O80.045 (2)0.048 (2)0.030 (2)−0.0025 (18)0.0073 (18)0.0041 (17)
N10.0148 (18)0.0161 (18)0.0143 (18)−0.0032 (15)0.0021 (15)0.0022 (14)
N20.0159 (18)0.0123 (16)0.0123 (18)−0.0028 (15)0.0025 (15)0.0016 (14)
N30.016 (2)0.020 (2)0.0119 (19)0.0079 (16)0.0007 (16)−0.0011 (16)
C10.015 (2)0.018 (2)0.012 (2)0.0004 (17)0.0061 (17)−0.0007 (17)
C20.012 (2)0.015 (2)0.012 (2)−0.0029 (16)0.0063 (17)−0.0028 (16)
C30.014 (2)0.0087 (18)0.015 (2)−0.0008 (16)0.0048 (17)0.0007 (16)
C40.012 (2)0.016 (2)0.008 (2)0.0043 (16)0.0079 (16)0.0038 (15)
C50.016 (2)0.015 (2)0.007 (2)0.0024 (17)0.0066 (17)−0.0019 (16)
C60.016 (2)0.014 (2)0.009 (2)0.0023 (17)0.0058 (16)0.0007 (16)
C70.011 (2)0.015 (2)0.012 (2)−0.0010 (16)0.0038 (17)−0.0002 (16)
C80.019 (2)0.018 (2)0.019 (2)−0.0020 (18)0.0045 (19)−0.0012 (18)
C90.015 (2)0.011 (2)0.024 (3)0.0017 (16)0.0021 (19)0.0002 (17)
Geometric parameters (Å, °) top
Cl1—C41.738 (4)N2—C11.337 (5)
S1—O21.415 (3)N2—C21.394 (5)
S1—O11.425 (3)N2—H1N0.89 (5)
S1—N11.625 (3)N3—H2N0.95 (5)
S1—C71.752 (4)N3—H3N0.75 (5)
S2—O41.429 (3)C1—H10.9500
S2—O31.442 (3)C2—C71.392 (5)
S2—N31.577 (4)C2—C31.402 (5)
S2—C51.783 (4)C3—C41.377 (5)
O5—C81.317 (5)C3—H30.9500
O5—H1H0.95 (6)C4—C51.413 (5)
O6—C81.199 (5)C5—C61.393 (5)
O7—C91.221 (5)C6—C71.387 (5)
O8—C91.324 (5)C6—H60.9500
O8—H2H1.10 (5)C8—H80.9500
N1—C11.306 (5)C9—H90.9500
?···??
O2—S1—O1116.85 (19)C7—C2—N2120.5 (3)
O2—S1—N1108.88 (18)C7—C2—C3119.7 (3)
O1—S1—N1107.28 (18)N2—C2—C3119.8 (3)
O2—S1—C7109.66 (18)C4—C3—C2119.0 (3)
O1—S1—C7108.27 (19)C4—C3—H3120.5
N1—S1—C7105.26 (18)C2—C3—H3120.5
O4—S2—O3118.90 (18)C3—C4—C5122.0 (3)
O4—S2—N3108.45 (19)C3—C4—Cl1117.2 (3)
O3—S2—N3109.52 (19)C5—C4—Cl1120.8 (3)
O4—S2—C5106.48 (17)C6—C5—C4118.0 (3)
O3—S2—C5105.71 (17)C6—C5—S2117.3 (3)
N3—S2—C5107.16 (19)C4—C5—S2124.6 (3)
C8—O5—H1H109 (3)C7—C6—C5120.4 (4)
C9—O8—H2H122 (3)C7—C6—H6119.8
C1—N1—S1121.3 (3)C5—C6—H6119.8
C1—N2—C2123.6 (4)C6—C7—C2120.8 (3)
C1—N2—H1N119 (3)C6—C7—S1119.4 (3)
C2—N2—H1N117 (3)C2—C7—S1119.8 (3)
S2—N3—H2N112 (3)O6—C8—O5124.6 (4)
S2—N3—H3N116 (4)O6—C8—H8117.7
H2N—N3—H3N125 (5)O5—C8—H8117.7
N1—C1—N2127.7 (4)O7—C9—O8125.2 (4)
N1—C1—H1116.2O7—C9—H9117.4
N2—C1—H1116.2O8—C9—H9117.4
O2—S1—N1—C1−131.6 (3)O4—S2—C5—C4−55.1 (4)
O1—S1—N1—C1101.1 (4)O3—S2—C5—C4177.6 (3)
C7—S1—N1—C1−14.1 (4)N3—S2—C5—C460.8 (4)
S1—N1—C1—N26.7 (6)C4—C5—C6—C71.0 (6)
C2—N2—C1—N15.0 (7)S2—C5—C6—C7−174.1 (3)
C1—N2—C2—C7−5.2 (6)C5—C6—C7—C21.2 (6)
C1—N2—C2—C3174.0 (4)C5—C6—C7—S1−177.7 (3)
C7—C2—C3—C43.0 (6)N2—C2—C7—C6175.9 (4)
N2—C2—C3—C4−176.2 (4)C3—C2—C7—C6−3.3 (6)
C2—C3—C4—C5−0.8 (6)N2—C2—C7—S1−5.1 (6)
C2—C3—C4—Cl1178.8 (3)C3—C2—C7—S1175.7 (3)
C3—C4—C5—C6−1.2 (6)O2—S1—C7—C6−50.7 (4)
Cl1—C4—C5—C6179.3 (3)O1—S1—C7—C677.8 (4)
C3—C4—C5—S2173.5 (3)N1—S1—C7—C6−167.7 (3)
Cl1—C4—C5—S2−6.1 (5)O2—S1—C7—C2130.3 (3)
O4—S2—C5—C6119.6 (3)O1—S1—C7—C2−101.1 (4)
O3—S2—C5—C6−7.7 (4)N1—S1—C7—C213.3 (4)
N3—S2—C5—C6−124.5 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O5—H1H···O70.95 (6)1.64 (6)2.593 (5)175 (6)
N2—H1N···O6i0.88 (4)1.83 (4)2.690 (4)166 (5)
O8—H2H···O31.10 (6)2.02 (5)3.027 (5)152 (4)
N3—H2N···N1ii0.94 (5)2.09 (5)3.022 (5)171 (4)
N3—H3N···O7iii0.76 (5)2.13 (5)2.890 (5)178 (6)
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x−1, y, z−1; (iii) x, y, z−1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O5—H1H···O70.95 (6)1.64 (6)2.593 (5)175 (6)
N2—H1N···O6i0.88 (4)1.83 (4)2.690 (4)166 (5)
O8—H2H···O31.10 (6)2.02 (5)3.027 (5)152 (4)
N3—H2N···N1ii0.94 (5)2.09 (5)3.022 (5)171 (4)
N3—H3N···O7iii0.76 (5)2.13 (5)2.890 (5)178 (6)
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x−1, y, z−1; (iii) x, y, z−1.
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 (http://www.cposs.org.uk).

references
References top

Dupont, L. & Dideberg, O. (1970). Acta Cryst. B26, 1884–1885.

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.

Hooft, R. (1988). COLLECT. Nonius BV, Delft, The Netherlands.

Johnston, A., Florence, A. J., Fernandes, P. & Kennedy, A. R. (2007a). Acta Cryst. E63, o2422–?.

Johnston, A., Florence, A. J., Fernandes, P. & Kennedy, A. R. (2007b). Acta Cryst. E63, o2423–?.

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

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.

Shankland, K., David, W. I. F. & Sivia, D. S. (1997). J. Mater. Chem. 7, 569–?.

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

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