Chloro­thia­zide formic acid solvate (1/2)

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.

Key indicators

• Single-crystal X-ray study
• T = 123 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.052
• wR factor = 0.114
• Data-to-parameter ratio = 11.6

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT029_ALERT_3_A _diffrn_measured_fraction_theta_full Low .......       0.93

Author Response: Intermitant fault with DX drive (sample to detector distance) led to one shell of data being unsuitable for inclusion in final refinement. Considering the decent quality of the final model and a reflections to parameters ratio > 10:1, we concluded that a repeat data collection was not required.

Alert level B
PLAT355_ALERT_3_B Long    O-H Bond (0.82A)   O8     -   H2H    ...       1.10 Ang.

Alert level C
REFLT03_ALERT_3_C  Reflection count < 95% complete
           From the CIF: _diffrn_reflns_theta_max           26.00
           From the CIF: _diffrn_reflns_theta_full          26.00
           From the CIF: _reflns_number_total               2650
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns         2845
           Completeness (_total/calc)             93.15%
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ....       0.93
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          6
PLAT352_ALERT_3_C Short   N-H Bond (0.87A)   N3     -   H3N    ...       0.76 Ang.
PLAT432_ALERT_2_C Short Inter X...Y Contact  O4     ..  C1      ..       3.00 Ang.
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              C H2 O2

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

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   6 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

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

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).

S2. Experimental

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

S3. Refinement

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 U_iso(H)=1.2U_eq(C) and C—H=0.95 Å.

Computing details

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

	Fig. 1. Molecular structure of title compound, showing 50% probablility displacement ellipsoids.
	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

Crystal data

C7H6ClN3O4S2·2CH2O2	F(000) = 792
Mr = 387.77	Dx = 1.789 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.2985 (5) Å	Cell parameters from 2389 reflections
b = 21.5271 (14) Å	θ = 1.0–27.5°
c = 8.3676 (5) Å	µ = 0.60 mm^−1
β = 105.580 (3)°	T = 123 K
V = 1439.89 (15) Å^3	Block, colourless
Z = 4	0.30 × 0.12 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer	1872 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.079
Graphite monochromator	θmax = 26.0°, θmin = 1.9°
phi and ω scans	h = −10→10
8698 measured reflections	k = −26→26
2650 independent reflections	l = −10→10

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.052	w = 1/[σ^2(Fo^2) + (0.0295P)^2 + 2.9523P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.114	(Δ/σ)max = 0.002
S = 1.07	Δρmax = 0.49 e Å^−3
2650 reflections	Δρmin = −0.53 e Å^−3
228 parameters

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
Cl1	0.58237 (12)	0.27340 (4)	0.40275 (12)	0.0165 (3)
S1	1.15604 (12)	0.13926 (4)	0.92688 (12)	0.0142 (3)
S2	0.57857 (12)	0.12000 (4)	0.43857 (12)	0.0132 (3)
O1	1.2736 (3)	0.11880 (14)	0.8414 (4)	0.0241 (7)
O2	1.0919 (4)	0.09369 (13)	1.0152 (4)	0.0231 (7)
O3	0.6350 (3)	0.05729 (12)	0.4813 (3)	0.0160 (7)
O4	0.4262 (3)	0.14023 (13)	0.4706 (3)	0.0188 (7)
O5	0.9981 (4)	0.00567 (13)	1.2892 (4)	0.0218 (7)
O6	1.0024 (4)	0.10413 (12)	1.3725 (4)	0.0227 (7)
O7	0.7176 (4)	0.03970 (14)	1.0859 (4)	0.0232 (7)
O8	0.5671 (5)	0.04283 (17)	0.8172 (5)	0.0418 (10)
N1	1.2463 (4)	0.19341 (15)	1.0552 (4)	0.0154 (8)
N2	1.1002 (4)	0.27635 (16)	0.8923 (4)	0.0137 (7)
N3	0.5668 (5)	0.13232 (18)	0.2500 (4)	0.0165 (8)
C1	1.2150 (5)	0.25210 (19)	1.0209 (5)	0.0142 (9)
H1	1.2817	0.2810	1.0963	0.017*
C2	0.9839 (5)	0.24083 (17)	0.7773 (5)	0.0124 (9)
C3	0.8579 (5)	0.27031 (17)	0.6553 (5)	0.0125 (9)
H3	0.8550	0.3143	0.6462	0.015*
C4	0.7382 (5)	0.23454 (17)	0.5490 (5)	0.0113 (8)
C5	0.7398 (5)	0.16901 (18)	0.5576 (5)	0.0122 (8)
C6	0.8692 (5)	0.14063 (18)	0.6763 (5)	0.0128 (8)
H6	0.8744	0.0966	0.6837	0.015*
C7	0.9906 (5)	0.17624 (17)	0.7838 (5)	0.0126 (9)
C8	1.0677 (5)	0.05427 (18)	1.3764 (5)	0.0187 (10)
H8	1.1774	0.0495	1.4475	0.022*
C9	0.7036 (5)	0.03154 (18)	0.9384 (5)	0.0173 (9)
H9	0.7983	0.0158	0.9081	0.021*
H1H	0.898 (7)	0.018 (3)	1.210 (7)	0.058 (18)*
H2H	0.562 (6)	0.036 (2)	0.686 (7)	0.045 (15)*
H1N	1.086 (6)	0.317 (2)	0.887 (6)	0.040 (15)*
H2N	0.470 (6)	0.155 (2)	0.197 (6)	0.032 (13)*
H3N	0.608 (6)	0.108 (2)	0.209 (6)	0.034 (17)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0158 (5)	0.0160 (5)	0.0156 (5)	0.0048 (4)	0.0004 (4)	0.0034 (4)
S1	0.0124 (5)	0.0133 (5)	0.0146 (6)	0.0017 (4)	−0.0005 (4)	0.0012 (4)
S2	0.0125 (5)	0.0133 (5)	0.0130 (5)	0.0001 (4)	0.0019 (4)	−0.0009 (4)
O1	0.0166 (16)	0.0281 (17)	0.0267 (18)	0.0082 (13)	0.0041 (13)	−0.0070 (14)
O2	0.0241 (17)	0.0187 (15)	0.0228 (17)	−0.0064 (13)	−0.0001 (14)	0.0077 (13)
O3	0.0177 (16)	0.0113 (14)	0.0173 (15)	−0.0035 (12)	0.0015 (12)	0.0002 (11)
O4	0.0122 (15)	0.0221 (15)	0.0225 (17)	0.0012 (12)	0.0053 (13)	−0.0026 (12)
O5	0.0236 (17)	0.0136 (15)	0.0238 (18)	0.0023 (13)	−0.0012 (14)	−0.0027 (13)
O6	0.0251 (17)	0.0120 (15)	0.0317 (19)	0.0034 (13)	0.0089 (14)	0.0009 (13)
O7	0.0238 (17)	0.0293 (17)	0.0147 (17)	0.0054 (14)	0.0020 (13)	−0.0046 (13)
O8	0.045 (2)	0.048 (2)	0.030 (2)	−0.0025 (18)	0.0073 (18)	0.0041 (17)
N1	0.0148 (18)	0.0161 (18)	0.0143 (18)	−0.0032 (15)	0.0021 (15)	0.0022 (14)
N2	0.0159 (18)	0.0123 (16)	0.0123 (18)	−0.0028 (15)	0.0025 (15)	0.0016 (14)
N3	0.016 (2)	0.020 (2)	0.0119 (19)	0.0079 (16)	0.0007 (16)	−0.0011 (16)
C1	0.015 (2)	0.018 (2)	0.012 (2)	0.0004 (17)	0.0061 (17)	−0.0007 (17)
C2	0.012 (2)	0.015 (2)	0.012 (2)	−0.0029 (16)	0.0063 (17)	−0.0028 (16)
C3	0.014 (2)	0.0087 (18)	0.015 (2)	−0.0008 (16)	0.0048 (17)	0.0007 (16)
C4	0.012 (2)	0.016 (2)	0.008 (2)	0.0043 (16)	0.0079 (16)	0.0038 (15)
C5	0.016 (2)	0.015 (2)	0.007 (2)	0.0024 (17)	0.0066 (17)	−0.0019 (16)
C6	0.016 (2)	0.014 (2)	0.009 (2)	0.0023 (17)	0.0058 (16)	0.0007 (16)
C7	0.011 (2)	0.015 (2)	0.012 (2)	−0.0010 (16)	0.0038 (17)	−0.0002 (16)
C8	0.019 (2)	0.018 (2)	0.019 (2)	−0.0020 (18)	0.0045 (19)	−0.0012 (18)
C9	0.015 (2)	0.011 (2)	0.024 (3)	0.0017 (16)	0.0021 (19)	0.0002 (17)

Geometric parameters (Å, º)

Cl1—C4	1.738 (4)	N2—C1	1.337 (5)
S1—O2	1.415 (3)	N2—C2	1.394 (5)
S1—O1	1.425 (3)	N2—H1N	0.89 (5)
S1—N1	1.625 (3)	N3—H2N	0.95 (5)
S1—C7	1.752 (4)	N3—H3N	0.75 (5)
S2—O4	1.429 (3)	C1—H1	0.9500
S2—O3	1.442 (3)	C2—C7	1.392 (5)
S2—N3	1.577 (4)	C2—C3	1.402 (5)
S2—C5	1.783 (4)	C3—C4	1.377 (5)
O5—C8	1.317 (5)	C3—H3	0.9500
O5—H1H	0.95 (6)	C4—C5	1.413 (5)
O6—C8	1.199 (5)	C5—C6	1.393 (5)
O7—C9	1.221 (5)	C6—C7	1.387 (5)
O8—C9	1.324 (5)	C6—H6	0.9500
O8—H2H	1.10 (5)	C8—H8	0.9500
N1—C1	1.306 (5)	C9—H9	0.9500
O2—S1—O1	116.85 (19)	C7—C2—N2	120.5 (3)
O2—S1—N1	108.88 (18)	C7—C2—C3	119.7 (3)
O1—S1—N1	107.28 (18)	N2—C2—C3	119.8 (3)
O2—S1—C7	109.66 (18)	C4—C3—C2	119.0 (3)
O1—S1—C7	108.27 (19)	C4—C3—H3	120.5
N1—S1—C7	105.26 (18)	C2—C3—H3	120.5
O4—S2—O3	118.90 (18)	C3—C4—C5	122.0 (3)
O4—S2—N3	108.45 (19)	C3—C4—Cl1	117.2 (3)
O3—S2—N3	109.52 (19)	C5—C4—Cl1	120.8 (3)
O4—S2—C5	106.48 (17)	C6—C5—C4	118.0 (3)
O3—S2—C5	105.71 (17)	C6—C5—S2	117.3 (3)
N3—S2—C5	107.16 (19)	C4—C5—S2	124.6 (3)
C8—O5—H1H	109 (3)	C7—C6—C5	120.4 (4)
C9—O8—H2H	122 (3)	C7—C6—H6	119.8
C1—N1—S1	121.3 (3)	C5—C6—H6	119.8
C1—N2—C2	123.6 (4)	C6—C7—C2	120.8 (3)
C1—N2—H1N	119 (3)	C6—C7—S1	119.4 (3)
C2—N2—H1N	117 (3)	C2—C7—S1	119.8 (3)
S2—N3—H2N	112 (3)	O6—C8—O5	124.6 (4)
S2—N3—H3N	116 (4)	O6—C8—H8	117.7
H2N—N3—H3N	125 (5)	O5—C8—H8	117.7
N1—C1—N2	127.7 (4)	O7—C9—O8	125.2 (4)
N1—C1—H1	116.2	O7—C9—H9	117.4
N2—C1—H1	116.2	O8—C9—H9	117.4
O2—S1—N1—C1	−131.6 (3)	O4—S2—C5—C4	−55.1 (4)
O1—S1—N1—C1	101.1 (4)	O3—S2—C5—C4	177.6 (3)
C7—S1—N1—C1	−14.1 (4)	N3—S2—C5—C4	60.8 (4)
S1—N1—C1—N2	6.7 (6)	C4—C5—C6—C7	1.0 (6)
C2—N2—C1—N1	5.0 (7)	S2—C5—C6—C7	−174.1 (3)
C1—N2—C2—C7	−5.2 (6)	C5—C6—C7—C2	1.2 (6)
C1—N2—C2—C3	174.0 (4)	C5—C6—C7—S1	−177.7 (3)
C7—C2—C3—C4	3.0 (6)	N2—C2—C7—C6	175.9 (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—Cl1	178.8 (3)	C3—C2—C7—S1	175.7 (3)
C3—C4—C5—C6	−1.2 (6)	O2—S1—C7—C6	−50.7 (4)
Cl1—C4—C5—C6	179.3 (3)	O1—S1—C7—C6	77.8 (4)
C3—C4—C5—S2	173.5 (3)	N1—S1—C7—C6	−167.7 (3)
Cl1—C4—C5—S2	−6.1 (5)	O2—S1—C7—C2	130.3 (3)
O4—S2—C5—C6	119.6 (3)	O1—S1—C7—C2	−101.1 (4)
O3—S2—C5—C6	−7.7 (4)	N1—S1—C7—C2	13.3 (4)
N3—S2—C5—C6	−124.5 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H1H···O7	0.95 (6)	1.64 (6)	2.593 (5)	175 (6)
N2—H1N···O6^i	0.88 (4)	1.83 (4)	2.690 (4)	166 (5)
O8—H2H···O3	1.10 (6)	2.02 (5)	3.027 (5)	152 (4)
N3—H2N···N1^ii	0.94 (5)	2.09 (5)	3.022 (5)	171 (4)
N3—H3N···O7^iii	0.76 (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.