(S)-Trichlormethia­zide

In the title compound [systematic name: 6-chloro-3-(dichlorometh­yl)-3,4-dihydro-2H-1,2,4-benzothia­diazine-7-sulfonamide 1,1-dioxide], C₈H₈Cl₃N₃O₄S₂, N—H...O and N—H...N inter­actions combine to create a three-dimensional hydrogen-bonded network.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.032
• wR factor = 0.079
• Data-to-parameter ratio = 12.8

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.92
PLAT094_ALERT_2_C Ratio of Maximum / Minimum Residual Density ....       2.56
PLAT230_ALERT_2_C Hirshfeld Test Diff for    Cl2    -   C8      ..       5.31 su
PLAT431_ALERT_2_C Short Inter HL..A Contact  Cl3    ..  O2      ..       3.23 Ang.
PLAT432_ALERT_2_C Short Inter X...Y Contact  Cl2    ..  C1      ..       3.16 Ang.
PLAT731_ALERT_1_C Bond    Calc     0.88(3), Rep   0.877(10) ......       3.00 su-Ra
              N3   -H7      1.555   1.555
PLAT731_ALERT_1_C Bond    Calc     0.88(3), Rep   0.876(10) ......       3.00 su-Ra
              N3   -H8      1.555   1.555

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      0.924
            Tmax scaled      0.924 Tmin scaled      0.859
REFLT03_ALERT_4_G  WARNING: Large fraction of Friedel related reflns may
                     be needed to determine absolute structure
           From the CIF: _diffrn_reflns_theta_max           28.51
           From the CIF: _reflns_number_total               2426
           Count of symmetry unique reflns         1984
           Completeness (_total/calc)            122.28%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       442
           Fraction of Friedel pairs measured     0.223
           Are heavy atom types Z>Si present        yes
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C7     = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          2

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

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 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


checkCIF publication errors

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: All authors have made a contribution to the structure report. Specifically, Fernandes, Johnston, Shankland N and Florence were responsible for the crystallisation screening and powder diffraction fingerprinting that resulted in the title compound. Leech, David and Shankland K were responsible for the structure solution and refinement.

   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

---

S1. Comment

Trichlormethiazide (TCMT) is a thiazide diuretic used in in the treatment of hypertension and here we report the single-crystal structure at 150 K (Fig. 1). 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).

Molecules crystallize in orthorhombic space group P2₁2₁2₁ with one molecule in the asymmetric unit. One N—H···N and three N—H···O intermolecular interactions combine to create a three-dimensional hydrogen-bonded network. The N—H···N contact links molecules to form an infinite hydrogen bonded chain along [001]. Contacts N2—H5···O4 and N3—H8···O1 combine to form an R₂²(16) (Etter, 1990) motif (Fig. 2) that stacks along the direction [100] with adjacent stacks connected via N3—H7···O3.

Related literature

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

For related literature, see: Etter (1990).

S2. Experimental

The compound was sourced from Sigma-Aldrich and a single-crystal sample was recrystallized from a saturated acetonitrile solution by isothermal solvent evaporation at room temperature.

S3. Refinement

The positions of all the H atoms were obtained from the use of difference Fourier maps. In the final refinement, all H atoms were constrained to geometrically sensible positions with a riding model [C—H = 0.95–1.00 Å and U_iso(H) = 1.2U_eq(C)], except for H5, which was allowed to refine freely, and H7 and H8, which were allowed to refine subject to a distance restraint [N—H = 0.88 (1) Å and U_iso(H) = 1.2U_eq(N)]. The highest density peak in the final differnce Fourier is 1.07 Å from atom Cl3.

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) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: enCIFer (Allen et al., 2004) and publCIF (Westrip, 2007).

Figures

	Fig. 1. The molecular structure showing 50% probablility displacement ellipsoids.
	Fig. 2. The R2^2(16) hydrogen-bond motif in the crystal structure. Hydrogen bonds are indicated by dashed lines.

6-chloro-3-(dichloromethyl)-3,4-dihydro-2H-1,2,4-benzothiadazine- 7-sulfonamide 1,1-dioxide

Crystal data

C8H8Cl3N3O4S2	F(000) = 768
Mr = 380.64	Dx = 1.853 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 10438 reflections
a = 8.7881 (2) Å	θ = 2.4–28.5°
b = 9.7924 (2) Å	µ = 0.99 mm^−1
c = 15.8527 (3) Å	T = 150 K
V = 1364.23 (5) Å^3	Block, colourless
Z = 4	0.18 × 0.09 × 0.08 mm

Data collection

Oxford Diffraction Gemini diffractometer	2426 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2345 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
Detector resolution: 15.9745 pixels mm^-1	θmax = 28.5°, θmin = 2.4°
ω and π scans	h = −11→11
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	k = −12→12
Tmin = 0.930, Tmax = 1.000	l = −20→21
16293 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.032	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.079	w = 1/[σ^2(Fo^2) + (0.0406P)^2 + 1.852P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
2426 reflections	Δρmax = 1.09 e Å^−3
190 parameters	Δρmin = −0.43 e Å^−3
2 restraints	Absolute structure: Flack (1983), 1013 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (9)

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
S1	0.14654 (10)	0.06986 (8)	0.09856 (5)	0.01639 (18)
Cl1	0.16750 (10)	0.70063 (8)	0.14482 (5)	0.0227 (2)
S2	0.10072 (9)	0.57477 (8)	−0.04076 (5)	0.01492 (18)
Cl3	0.22251 (13)	−0.16217 (10)	0.34050 (6)	0.0351 (3)
Cl2	0.46909 (11)	0.03493 (14)	0.33187 (7)	0.0439 (3)
O3	−0.0121 (3)	0.6738 (2)	−0.02101 (14)	0.0219 (5)
O4	0.0781 (3)	0.4843 (2)	−0.11050 (14)	0.0208 (5)
O2	0.2201 (3)	0.0264 (2)	0.02376 (15)	0.0268 (6)
O1	−0.0074 (3)	0.0296 (3)	0.11374 (16)	0.0265 (6)
N3	0.2576 (3)	0.6584 (3)	−0.05901 (17)	0.0173 (6)
H7	0.276 (4)	0.716 (3)	−0.0177 (16)	0.021*
H8	0.339 (3)	0.608 (3)	−0.067 (2)	0.021*
C6	0.1876 (4)	0.3021 (3)	0.19017 (19)	0.0152 (7)
C5	0.1573 (4)	0.2474 (3)	0.1092 (2)	0.0154 (7)
C2	0.1626 (4)	0.5259 (3)	0.1290 (2)	0.0156 (7)
N1	0.2182 (4)	0.2223 (3)	0.25852 (17)	0.0199 (6)
H3	0.2533	0.2612	0.3047	0.024*
C3	0.1318 (4)	0.4710 (3)	0.0488 (2)	0.0147 (7)
C4	0.1312 (4)	0.3306 (3)	0.0401 (2)	0.0152 (6)
H2	0.1127	0.2909	−0.0137	0.018*
C7	0.1953 (4)	0.0768 (4)	0.25786 (19)	0.0180 (7)
H4	0.0835	0.0595	0.2626	0.022*
N2	0.2475 (4)	0.0172 (3)	0.17859 (17)	0.0195 (6)
H5	0.350 (5)	0.023 (4)	0.174 (2)	0.023*
C1	0.1896 (4)	0.4449 (3)	0.1979 (2)	0.0174 (7)
H1	0.2098	0.4857	0.2511	0.021*
C8	0.2723 (4)	0.0121 (4)	0.3342 (2)	0.0232 (8)
H6	0.2325	0.0585	0.3859	0.028*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0245 (4)	0.0128 (4)	0.0119 (4)	−0.0004 (3)	−0.0028 (3)	−0.0011 (3)
Cl1	0.0364 (5)	0.0130 (4)	0.0188 (4)	−0.0022 (3)	0.0006 (4)	−0.0032 (3)
S2	0.0146 (4)	0.0154 (4)	0.0147 (4)	0.0011 (3)	−0.0014 (3)	0.0012 (3)
Cl3	0.0606 (7)	0.0201 (4)	0.0247 (5)	−0.0014 (4)	−0.0097 (5)	0.0023 (4)
Cl2	0.0219 (5)	0.0729 (8)	0.0369 (6)	−0.0006 (5)	−0.0066 (4)	0.0091 (5)
O3	0.0193 (12)	0.0203 (12)	0.0261 (13)	0.0043 (10)	−0.0020 (10)	0.0001 (10)
O4	0.0275 (13)	0.0194 (12)	0.0156 (12)	0.0013 (10)	−0.0049 (10)	0.0012 (10)
O2	0.0429 (15)	0.0216 (12)	0.0158 (12)	0.0063 (12)	−0.0006 (12)	−0.0049 (10)
O1	0.0265 (14)	0.0222 (13)	0.0309 (14)	−0.0077 (11)	−0.0065 (11)	0.0008 (11)
N3	0.0178 (15)	0.0175 (14)	0.0165 (14)	0.0002 (12)	0.0020 (12)	0.0003 (12)
C6	0.0165 (17)	0.0169 (16)	0.0121 (15)	−0.0005 (14)	0.0008 (12)	0.0008 (13)
C5	0.0173 (16)	0.0142 (16)	0.0147 (16)	−0.0031 (13)	0.0023 (13)	0.0003 (13)
C2	0.0146 (16)	0.0140 (15)	0.0183 (16)	−0.0022 (13)	0.0045 (13)	−0.0039 (13)
N1	0.0323 (16)	0.0167 (14)	0.0106 (13)	−0.0011 (13)	−0.0017 (12)	−0.0002 (11)
C3	0.0141 (16)	0.0154 (15)	0.0146 (16)	−0.0013 (13)	0.0009 (13)	0.0022 (13)
C4	0.0167 (16)	0.0168 (15)	0.0122 (14)	−0.0005 (13)	−0.0002 (13)	−0.0019 (14)
C7	0.0223 (16)	0.0184 (16)	0.0134 (15)	0.0004 (14)	0.0001 (13)	−0.0007 (14)
N2	0.0241 (16)	0.0206 (14)	0.0137 (14)	0.0017 (13)	−0.0006 (12)	0.0004 (11)
C1	0.0204 (17)	0.0178 (17)	0.0141 (15)	−0.0013 (14)	0.0005 (13)	−0.0030 (14)
C8	0.033 (2)	0.0216 (17)	0.0151 (17)	−0.0007 (16)	−0.0071 (16)	0.0023 (14)

Geometric parameters (Å, º)

S1—O2	1.416 (3)	C6—C5	1.416 (4)
S1—O1	1.429 (3)	C5—C4	1.385 (4)
S1—N2	1.632 (3)	C2—C1	1.371 (5)
S1—C5	1.749 (3)	C2—C3	1.406 (5)
Cl1—C2	1.730 (3)	N1—C7	1.439 (5)
S2—O3	1.422 (2)	N1—H3	0.8800
S2—O4	1.430 (2)	C3—C4	1.382 (4)
S2—N3	1.630 (3)	C4—H2	0.9500
S2—C3	1.767 (3)	C7—N2	1.460 (4)
Cl3—C8	1.765 (4)	C7—C8	1.525 (5)
Cl2—C8	1.744 (4)	C7—H4	1.0000
N3—H7	0.877 (10)	N2—H5	0.91 (4)
N3—H8	0.876 (10)	C1—H1	0.9500
C6—N1	1.362 (4)	C8—H6	1.0000
C6—C1	1.405 (5)
O2—S1—O1	119.33 (17)	C7—N1—H3	118.9
O2—S1—N2	107.96 (15)	C4—C3—C2	118.1 (3)
O1—S1—N2	107.23 (16)	C4—C3—S2	119.4 (3)
O2—S1—C5	110.78 (15)	C2—C3—S2	122.4 (2)
O1—S1—C5	108.02 (15)	C3—C4—C5	120.3 (3)
N2—S1—C5	102.10 (16)	C3—C4—H2	119.8
O3—S2—O4	119.70 (14)	C5—C4—H2	119.8
O3—S2—N3	106.65 (15)	N1—C7—N2	111.0 (3)
O4—S2—N3	106.95 (15)	N1—C7—C8	110.1 (3)
O3—S2—C3	108.84 (15)	N2—C7—C8	112.2 (3)
O4—S2—C3	106.65 (14)	N1—C7—H4	107.8
N3—S2—C3	107.51 (14)	N2—C7—H4	107.8
S2—N3—H7	110 (3)	C8—C7—H4	107.8
S2—N3—H8	116 (3)	C7—N2—S1	111.9 (2)
H7—N3—H8	109 (4)	C7—N2—H5	111 (2)
N1—C6—C1	119.9 (3)	S1—N2—H5	117 (2)
N1—C6—C5	122.8 (3)	C2—C1—C6	120.3 (3)
C1—C6—C5	117.3 (3)	C2—C1—H1	119.9
C4—C5—C6	121.8 (3)	C6—C1—H1	119.9
C4—C5—S1	119.9 (2)	C7—C8—Cl2	111.7 (3)
C6—C5—S1	118.3 (2)	C7—C8—Cl3	109.7 (2)
C1—C2—C3	122.2 (3)	Cl2—C8—Cl3	111.8 (2)
C1—C2—Cl1	116.9 (2)	C7—C8—H6	107.8
C3—C2—Cl1	120.9 (3)	Cl2—C8—H6	107.8
C6—N1—C7	122.3 (3)	Cl3—C8—H6	107.8
C6—N1—H3	118.9

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H3···N3^i	0.88	2.30	3.127 (4)	156
N2—H5···O4^ii	0.91 (4)	2.24 (4)	3.099 (4)	157 (3)
N3—H7···O3^iii	0.88 (3)	2.24 (3)	2.899 (4)	132 (3)
N3—H8···O1^ii	0.88 (3)	2.05 (3)	2.900 (4)	164 (3)

Symmetry codes: (i) −x+1/2, −y+1, z+1/2; (ii) x+1/2, −y+1/2, −z; (iii) x+1/2, −y+3/2, −z.