Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807034137/lh2457sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807034137/lh2457Isup2.hkl |
CCDC reference: 660195
Key indicators
- Single-crystal X-ray study
- T = 150 K
- Mean (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
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.
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 Uiso(H) = 1.2Ueq(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 Uiso(H) = 1.2Ueq(N)]. The highest density peak in the final differnce Fourier is 1.07 Å from atom Cl3.
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.
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).
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).
Fig. 1. The molecular structure showing 50% probablility displacement ellipsoids. | |
Fig. 2. The R22(16) hydrogen-bond motif in the crystal structure. Hydrogen bonds are indicated by dashed lines. |
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) Å3 | Block, colourless |
Z = 4 | 0.18 × 0.09 × 0.08 mm |
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 on F2 | Secondary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Hydrogen site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.032 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.079 | w = 1/[σ2(Fo2) + (0.0406P)2 + 1.852P] where P = (Fo2 + 2Fc2)/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) |
C8H8Cl3N3O4S2 | V = 1364.23 (5) Å3 |
Mr = 380.64 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.7881 (2) Å | µ = 0.99 mm−1 |
b = 9.7924 (2) Å | T = 150 K |
c = 15.8527 (3) Å | 0.18 × 0.09 × 0.08 mm |
Oxford Diffraction Gemini diffractometer | 2426 independent reflections |
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006) | 2345 reflections with I > 2σ(I) |
Tmin = 0.930, Tmax = 1.000 | Rint = 0.030 |
16293 measured reflections |
R[F2 > 2σ(F2)] = 0.032 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.079 | Δρmax = 1.09 e Å−3 |
S = 1.06 | Δρmin = −0.43 e Å−3 |
2426 reflections | Absolute structure: Flack (1983), 1013 Friedel pairs |
190 parameters | Absolute structure parameter: −0.02 (9) |
2 restraints |
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. |
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* |
U11 | U22 | U33 | U12 | U13 | U23 | |
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) |
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 |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H3···N3i | 0.88 | 2.30 | 3.127 (4) | 156 |
N2—H5···O4ii | 0.91 (4) | 2.24 (4) | 3.099 (4) | 157 (3) |
N3—H7···O3iii | 0.88 (3) | 2.24 (3) | 2.899 (4) | 132 (3) |
N3—H8···O1ii | 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. |
Experimental details
Crystal data | |
Chemical formula | C8H8Cl3N3O4S2 |
Mr | 380.64 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 150 |
a, b, c (Å) | 8.7881 (2), 9.7924 (2), 15.8527 (3) |
V (Å3) | 1364.23 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.99 |
Crystal size (mm) | 0.18 × 0.09 × 0.08 |
Data collection | |
Diffractometer | Oxford Diffraction Gemini |
Absorption correction | Multi-scan (CrysAlis RED; Oxford Diffraction, 2006) |
Tmin, Tmax | 0.930, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 16293, 2426, 2345 |
Rint | 0.030 |
(sin θ/λ)max (Å−1) | 0.672 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.032, 0.079, 1.06 |
No. of reflections | 2426 |
No. of parameters | 190 |
No. of restraints | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 1.09, −0.43 |
Absolute structure | Flack (1983), 1013 Friedel pairs |
Absolute structure parameter | −0.02 (9) |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), CrysAlis RED, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003) and ORTEP-3 (Farrugia, 1997), enCIFer (Allen et al., 2004) and publCIF (Westrip, 2007).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H3···N3i | 0.8800 | 2.3000 | 3.127 (4) | 156.00 |
N2—H5···O4ii | 0.91 (4) | 2.24 (4) | 3.099 (4) | 157 (3) |
N3—H7···O3iii | 0.88 (3) | 2.24 (3) | 2.899 (4) | 132 (3) |
N3—H8···O1ii | 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. |
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.