Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107054443/gd3164sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270107054443/gd3164IIsup2.hkl |
CCDC reference: 682810
The raw material (a commercial sample of anhydrous rosiglitazone maleate, obtained from Dr Reddy's Laboratories) was recrystallized from ethyl acetate, and the title hydrate was reproducibly obtained, though in a low yield, as colourless needles suitable for single-crystal X-ray diffraction. The X-ray powder diffraction diagram of this product, (II), showed significant differences from the starting material, but since the solvent was used as bought, without further purification, the origin of the (depleted) solvent water molecule cannot be determined with certainty.
H atoms attached to C atoms were placed in geometrically idealized positions and allowed to ride, with C—H = 0.93–0.98 Å. H atoms bonded to N and O atoms in the organic components were clearly located in a difference Fourier map and were refined with restrained distances N—H = O—H = 0.85 (3) Å. In all cases, Uiso(H) = 1.2Ueq(parent).
The occupancy of the water molecule was clearly less than unity, and its site-occupancy factor refined to -0.5 [should this be ~0.5 ?]; the occupancy was then fixed at 0.5. The H atoms of the water component could not be found and were omitted from the model.
Data collection: SMART-NT (Bruker, 2001); cell refinement: SAINT-NT (Bruker, 2001); data reduction: SAINT-NT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-NT (Bruker, 2001); software used to prepare material for publication: SHELXTL-NT (Bruker, 2001) and PLATON (Spek, 2003).
C18H20N3O3S+·C4H3O4−·0.25H2O | Z = 4 |
Mr = 478.01 | F(000) = 1000 |
Triclinic, P1 | Dx = 1.388 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.3145 (8) Å | Cell parameters from 2567 reflections |
b = 12.3555 (10) Å | θ = 2.3–22.7° |
c = 20.8280 (17) Å | µ = 0.19 mm−1 |
α = 105.475 (2)° | T = 298 K |
β = 96.330 (3)° | Needle, colourless |
γ = 93.276 (2)° | 0.52 × 0.12 × 0.11 mm |
V = 2286.6 (3) Å3 |
Bruker Model? CCD area-detector diffractometer | 9856 independent reflections |
Radiation source: fine-focus sealed tube | 5102 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.058 |
ϕ and ω scans | θmax = 28.1°, θmin = 1.7° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | h = −12→12 |
Tmin = 0.90, Tmax = 0.98 | k = −15→15 |
19294 measured reflections | l = −27→26 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.063 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.154 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.95 | w = 1/[σ2(Fo2) + (0.0685P)2] where P = (Fo2 + 2Fc2)/3 |
9856 reflections | (Δ/σ)max < 0.001 |
624 parameters | Δρmax = 0.43 e Å−3 |
6 restraints | Δρmin = −0.26 e Å−3 |
C18H20N3O3S+·C4H3O4−·0.25H2O | γ = 93.276 (2)° |
Mr = 478.01 | V = 2286.6 (3) Å3 |
Triclinic, P1 | Z = 4 |
a = 9.3145 (8) Å | Mo Kα radiation |
b = 12.3555 (10) Å | µ = 0.19 mm−1 |
c = 20.8280 (17) Å | T = 298 K |
α = 105.475 (2)° | 0.52 × 0.12 × 0.11 mm |
β = 96.330 (3)° |
Bruker Model? CCD area-detector diffractometer | 9856 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | 5102 reflections with I > 2σ(I) |
Tmin = 0.90, Tmax = 0.98 | Rint = 0.058 |
19294 measured reflections |
R[F2 > 2σ(F2)] = 0.063 | 6 restraints |
wR(F2) = 0.154 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.95 | Δρmax = 0.43 e Å−3 |
9856 reflections | Δρmin = −0.26 e Å−3 |
624 parameters |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
S1A | 0.83045 (9) | 0.25951 (7) | 0.57547 (4) | 0.0576 (2) | |
O1A | 0.7512 (3) | 0.3157 (2) | 0.69688 (11) | 0.0803 (7) | |
O2A | 0.6478 (3) | 0.51656 (19) | 0.54675 (11) | 0.0935 (8) | |
O3A | 0.9801 (2) | −0.01814 (17) | 0.28142 (10) | 0.0584 (5) | |
N1A | 0.6965 (3) | 0.4307 (2) | 0.62982 (12) | 0.0532 (6) | |
H1NA | 0.642 (3) | 0.469 (2) | 0.6550 (12) | 0.064* | |
N2A | 1.0072 (3) | −0.1703 (2) | 0.15756 (12) | 0.0533 (6) | |
N3A | 0.8298 (3) | −0.3243 (2) | 0.13203 (13) | 0.0645 (7) | |
H3NA | 0.850 (3) | −0.350 (3) | 0.1670 (11) | 0.077* | |
C1A | 0.7539 (3) | 0.3394 (3) | 0.64472 (15) | 0.0536 (8) | |
C2A | 0.7016 (3) | 0.4430 (3) | 0.56702 (15) | 0.0566 (8) | |
C3A | 0.7790 (3) | 0.3518 (2) | 0.52401 (13) | 0.0498 (7) | |
H3A | 0.8668 | 0.3862 | 0.5128 | 0.060* | |
C4A | 0.6809 (3) | 0.2899 (3) | 0.45892 (14) | 0.0583 (8) | |
H4A1 | 0.5971 | 0.2517 | 0.4699 | 0.070* | |
H4A2 | 0.6466 | 0.3447 | 0.4364 | 0.070* | |
C5A | 0.7575 (3) | 0.2052 (2) | 0.41192 (13) | 0.0467 (7) | |
C6A | 0.8503 (3) | 0.2400 (2) | 0.37148 (14) | 0.0534 (8) | |
H6A | 0.8641 | 0.3161 | 0.3736 | 0.064* | |
C7A | 0.9212 (3) | 0.1634 (2) | 0.32878 (14) | 0.0496 (7) | |
H7A | 0.9805 | 0.1876 | 0.3012 | 0.060* | |
C8A | 0.9052 (3) | 0.0506 (2) | 0.32636 (14) | 0.0460 (7) | |
C9A | 0.8174 (3) | 0.0144 (2) | 0.36738 (14) | 0.0533 (8) | |
H9A | 0.8077 | −0.0612 | 0.3669 | 0.064* | |
C10A | 0.7441 (3) | 0.0928 (3) | 0.40918 (14) | 0.0540 (8) | |
H10A | 0.6839 | 0.0685 | 0.4363 | 0.065* | |
C11A | 0.9705 (3) | −0.1359 (2) | 0.27664 (14) | 0.0550 (8) | |
H11A | 0.8705 | −0.1679 | 0.2648 | 0.066* | |
H11B | 1.0082 | −0.1483 | 0.3191 | 0.066* | |
C12A | 1.0604 (3) | −0.1890 (3) | 0.22246 (14) | 0.0569 (8) | |
H12A | 1.1604 | −0.1574 | 0.2358 | 0.068* | |
H12B | 1.0578 | −0.2694 | 0.2176 | 0.068* | |
C13A | 1.0693 (4) | −0.0698 (3) | 0.14290 (16) | 0.0743 (10) | |
H13A | 1.0884 | −0.0885 | 0.0970 | 0.111* | |
H13B | 1.1582 | −0.0418 | 0.1722 | 0.111* | |
H13C | 1.0021 | −0.0130 | 0.1498 | 0.111* | |
C14A | 0.8922 (3) | −0.2315 (3) | 0.11774 (14) | 0.0516 (7) | |
C15A | 0.8302 (3) | −0.2054 (3) | 0.06092 (14) | 0.0560 (8) | |
H15A | 0.8687 | −0.1428 | 0.0497 | 0.067* | |
C16A | 0.7121 (4) | −0.2710 (3) | 0.02059 (16) | 0.0762 (10) | |
H16A | 0.6732 | −0.2529 | −0.0179 | 0.091* | |
C17A | 0.6515 (4) | −0.3623 (3) | 0.0365 (2) | 0.0828 (11) | |
H17A | 0.5704 | −0.4052 | 0.0099 | 0.099* | |
C18A | 0.7121 (4) | −0.3888 (3) | 0.09185 (19) | 0.0707 (10) | |
H18A | 0.6733 | −0.4516 | 0.1027 | 0.085* | |
S1B | 0.38884 (8) | 0.23694 (7) | 0.59213 (4) | 0.0574 (2) | |
O1B | 0.3568 (2) | 0.2727 (2) | 0.72028 (11) | 0.0757 (7) | |
O2B | 0.1208 (2) | 0.46134 (18) | 0.58703 (10) | 0.0675 (6) | |
O3B | 0.4261 (2) | −0.02971 (15) | 0.27328 (9) | 0.0566 (5) | |
N1B | 0.2267 (3) | 0.3735 (2) | 0.66051 (12) | 0.0561 (7) | |
H1NB | 0.185 (3) | 0.400 (2) | 0.6950 (10) | 0.067* | |
N2B | 0.4764 (3) | −0.1170 (2) | 0.12567 (12) | 0.0597 (7) | |
N3B | 0.3132 (3) | −0.2556 (2) | 0.05237 (12) | 0.0590 (7) | |
H3NB | 0.323 (3) | −0.233 (2) | 0.0174 (10) | 0.071* | |
C1B | 0.3235 (3) | 0.2972 (2) | 0.66881 (15) | 0.0525 (7) | |
C2B | 0.1998 (3) | 0.3939 (2) | 0.59881 (14) | 0.0486 (7) | |
C3B | 0.2802 (3) | 0.3173 (2) | 0.54768 (13) | 0.0466 (7) | |
H3B | 0.3449 | 0.3642 | 0.5299 | 0.056* | |
C4B | 0.1743 (3) | 0.2421 (3) | 0.48935 (14) | 0.0599 (8) | |
H4B1 | 0.1139 | 0.1927 | 0.5066 | 0.072* | |
H4B2 | 0.1113 | 0.2894 | 0.4710 | 0.072* | |
C5B | 0.2460 (3) | 0.1712 (3) | 0.43353 (14) | 0.0496 (7) | |
C6B | 0.3032 (3) | 0.2176 (3) | 0.38795 (15) | 0.0579 (8) | |
H6B | 0.2999 | 0.2945 | 0.3932 | 0.070* | |
C7B | 0.3656 (3) | 0.1548 (2) | 0.33458 (14) | 0.0526 (7) | |
H7B | 0.4031 | 0.1889 | 0.3045 | 0.063* | |
C8B | 0.3715 (3) | 0.0407 (2) | 0.32666 (13) | 0.0449 (7) | |
C9B | 0.3181 (3) | −0.0077 (2) | 0.37131 (14) | 0.0551 (8) | |
H9B | 0.3232 | −0.0843 | 0.3665 | 0.066* | |
C10B | 0.2555 (3) | 0.0579 (3) | 0.42457 (15) | 0.0591 (8) | |
H10B | 0.2191 | 0.0238 | 0.4549 | 0.071* | |
C11B | 0.5199 (3) | 0.0215 (2) | 0.23829 (14) | 0.0557 (8) | |
H11C | 0.5997 | 0.0669 | 0.2694 | 0.067* | |
H11D | 0.4674 | 0.0700 | 0.2162 | 0.067* | |
C12B | 0.5766 (3) | −0.0713 (3) | 0.18687 (14) | 0.0610 (8) | |
H12C | 0.6664 | −0.0422 | 0.1754 | 0.073* | |
H12D | 0.5987 | −0.1320 | 0.2068 | 0.073* | |
C13B | 0.4704 (4) | −0.0478 (3) | 0.07825 (16) | 0.0789 (10) | |
H13D | 0.4944 | −0.0911 | 0.0358 | 0.118* | |
H13E | 0.5384 | 0.0176 | 0.0957 | 0.118* | |
H13F | 0.3743 | −0.0247 | 0.0722 | 0.118* | |
C14B | 0.3927 (3) | −0.2145 (3) | 0.11324 (14) | 0.0500 (7) | |
C15B | 0.3815 (3) | −0.2773 (3) | 0.15966 (15) | 0.0576 (8) | |
H15B | 0.4336 | −0.2520 | 0.2024 | 0.069* | |
C16B | 0.2948 (4) | −0.3748 (3) | 0.14206 (18) | 0.0690 (9) | |
H16B | 0.2896 | −0.4173 | 0.1726 | 0.083* | |
C17B | 0.2126 (4) | −0.4131 (3) | 0.0784 (2) | 0.0800 (11) | |
H17B | 0.1512 | −0.4792 | 0.0668 | 0.096* | |
C18B | 0.2249 (4) | −0.3513 (3) | 0.03432 (17) | 0.0699 (9) | |
H18B | 0.1724 | −0.3750 | −0.0084 | 0.084* | |
O1C | 0.3046 (3) | 0.8045 (2) | 0.93542 (12) | 0.0986 (9) | |
O2C | 0.4279 (3) | 0.6563 (2) | 0.90212 (12) | 0.0940 (8) | |
O3C | 0.5276 (3) | 0.5631 (3) | 0.80131 (15) | 0.1010 (9) | |
H3OC | 0.501 (5) | 0.589 (4) | 0.8408 (11) | 0.121* | |
O4C | 0.5112 (3) | 0.5744 (2) | 0.69720 (14) | 0.0999 (8) | |
C1C | 0.3528 (4) | 0.7339 (3) | 0.89154 (18) | 0.0682 (9) | |
C2C | 0.3165 (3) | 0.7399 (3) | 0.82091 (16) | 0.0591 (8) | |
H2C | 0.2483 | 0.7898 | 0.8152 | 0.071* | |
C3C | 0.3662 (3) | 0.6854 (3) | 0.76549 (16) | 0.0623 (9) | |
H3C | 0.3255 | 0.7019 | 0.7268 | 0.075* | |
C4C | 0.4757 (4) | 0.6023 (3) | 0.7543 (2) | 0.0734 (10) | |
O4D | −0.2554 (4) | 0.8195 (3) | 0.8429 (2) | 0.1501 (14) | |
O3D | −0.1114 (4) | 0.7308 (3) | 0.89656 (17) | 0.1142 (10) | |
H3OD | −0.049 (4) | 0.683 (3) | 0.888 (2) | 0.137* | |
O2D | 0.0371 (3) | 0.5716 (2) | 0.86740 (11) | 0.0802 (7) | |
O1D | 0.0939 (3) | 0.4532 (2) | 0.77597 (12) | 0.0870 (8) | |
C4D | −0.1712 (5) | 0.7477 (4) | 0.8409 (3) | 0.0964 (13) | |
C3D | −0.1308 (4) | 0.6792 (4) | 0.7762 (2) | 0.0891 (13) | |
H3D | −0.1733 | 0.6987 | 0.7388 | 0.107* | |
C2D | −0.0466 (4) | 0.5960 (3) | 0.76152 (17) | 0.0746 (10) | |
H2D | −0.0361 | 0.5703 | 0.7162 | 0.089* | |
C1D | 0.0329 (3) | 0.5378 (3) | 0.80466 (18) | 0.0635 (9) | |
O1W | 0.1198 (6) | 0.9703 (6) | 0.9730 (3) | 0.137 (3) | 0.50 |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1A | 0.0614 (5) | 0.0605 (5) | 0.0556 (5) | 0.0166 (4) | 0.0104 (4) | 0.0207 (4) |
O1A | 0.1008 (18) | 0.0976 (18) | 0.0524 (14) | 0.0236 (15) | 0.0115 (13) | 0.0337 (14) |
O2A | 0.163 (3) | 0.0583 (15) | 0.0746 (17) | 0.0440 (16) | 0.0325 (17) | 0.0301 (13) |
O3A | 0.0620 (13) | 0.0528 (13) | 0.0615 (13) | 0.0085 (10) | 0.0199 (11) | 0.0119 (11) |
N1A | 0.0573 (16) | 0.0519 (17) | 0.0480 (17) | 0.0050 (13) | 0.0117 (12) | 0.0078 (13) |
N2A | 0.0566 (16) | 0.0553 (16) | 0.0488 (15) | 0.0075 (13) | 0.0077 (13) | 0.0148 (13) |
N3A | 0.0712 (19) | 0.0628 (19) | 0.0595 (18) | 0.0119 (15) | 0.0126 (16) | 0.0140 (15) |
C1A | 0.0529 (18) | 0.060 (2) | 0.0464 (19) | 0.0039 (15) | −0.0019 (14) | 0.0152 (16) |
C2A | 0.077 (2) | 0.0459 (19) | 0.0448 (19) | 0.0005 (16) | 0.0074 (16) | 0.0092 (15) |
C3A | 0.0552 (18) | 0.0466 (17) | 0.0460 (17) | 0.0000 (14) | 0.0073 (14) | 0.0107 (14) |
C4A | 0.0592 (19) | 0.062 (2) | 0.0509 (19) | 0.0131 (16) | 0.0019 (15) | 0.0106 (16) |
C5A | 0.0488 (17) | 0.0525 (19) | 0.0351 (16) | 0.0087 (14) | −0.0026 (13) | 0.0081 (14) |
C6A | 0.063 (2) | 0.0490 (19) | 0.0462 (18) | 0.0049 (16) | −0.0025 (15) | 0.0142 (15) |
C7A | 0.0517 (18) | 0.0511 (19) | 0.0459 (17) | −0.0026 (14) | 0.0053 (14) | 0.0150 (15) |
C8A | 0.0439 (16) | 0.0476 (18) | 0.0428 (17) | 0.0025 (14) | 0.0022 (13) | 0.0076 (14) |
C9A | 0.0641 (19) | 0.0451 (18) | 0.0512 (18) | 0.0009 (15) | 0.0128 (16) | 0.0127 (15) |
C10A | 0.0611 (19) | 0.055 (2) | 0.0450 (18) | −0.0034 (16) | 0.0105 (15) | 0.0133 (15) |
C11A | 0.0601 (19) | 0.053 (2) | 0.0516 (18) | 0.0086 (15) | 0.0061 (15) | 0.0127 (15) |
C12A | 0.0521 (18) | 0.060 (2) | 0.0541 (19) | 0.0117 (15) | 0.0012 (15) | 0.0085 (16) |
C13A | 0.073 (2) | 0.079 (2) | 0.074 (2) | 0.0014 (19) | 0.0200 (19) | 0.024 (2) |
C14A | 0.0525 (18) | 0.0539 (19) | 0.0464 (18) | 0.0140 (16) | 0.0121 (15) | 0.0064 (15) |
C15A | 0.0584 (19) | 0.072 (2) | 0.0440 (18) | 0.0167 (17) | 0.0099 (15) | 0.0228 (16) |
C16A | 0.073 (2) | 0.103 (3) | 0.045 (2) | 0.021 (2) | 0.0009 (18) | 0.008 (2) |
C17A | 0.062 (2) | 0.084 (3) | 0.082 (3) | 0.006 (2) | −0.002 (2) | −0.008 (2) |
C18A | 0.065 (2) | 0.056 (2) | 0.079 (3) | −0.0011 (18) | 0.008 (2) | −0.0002 (19) |
S1B | 0.0526 (5) | 0.0627 (5) | 0.0590 (5) | 0.0110 (4) | 0.0071 (4) | 0.0191 (4) |
O1B | 0.0804 (16) | 0.0943 (17) | 0.0556 (14) | 0.0003 (13) | −0.0060 (12) | 0.0334 (13) |
O2B | 0.0758 (15) | 0.0606 (14) | 0.0685 (15) | 0.0235 (12) | 0.0105 (12) | 0.0179 (12) |
O3B | 0.0653 (13) | 0.0478 (12) | 0.0526 (12) | 0.0023 (10) | 0.0183 (10) | 0.0033 (10) |
N1B | 0.0607 (17) | 0.0619 (18) | 0.0423 (16) | 0.0017 (14) | 0.0107 (12) | 0.0079 (14) |
N2B | 0.0758 (18) | 0.0600 (17) | 0.0415 (15) | 0.0043 (15) | 0.0082 (13) | 0.0110 (13) |
N3B | 0.0769 (18) | 0.0598 (18) | 0.0410 (16) | 0.0076 (15) | 0.0120 (14) | 0.0129 (14) |
C1B | 0.0521 (18) | 0.0529 (19) | 0.0509 (19) | −0.0067 (15) | 0.0001 (15) | 0.0166 (16) |
C2B | 0.0517 (18) | 0.0455 (18) | 0.0471 (19) | −0.0011 (15) | 0.0059 (14) | 0.0113 (15) |
C3B | 0.0491 (16) | 0.0495 (17) | 0.0427 (17) | 0.0031 (14) | 0.0064 (13) | 0.0152 (14) |
C4B | 0.0497 (18) | 0.074 (2) | 0.0466 (18) | 0.0085 (16) | 0.0013 (14) | 0.0018 (16) |
C5B | 0.0446 (17) | 0.056 (2) | 0.0431 (17) | 0.0055 (14) | −0.0009 (13) | 0.0071 (15) |
C6B | 0.067 (2) | 0.0476 (19) | 0.0560 (19) | 0.0119 (16) | 0.0033 (16) | 0.0100 (16) |
C7B | 0.0609 (19) | 0.0500 (19) | 0.0498 (18) | 0.0083 (15) | 0.0108 (15) | 0.0167 (15) |
C8B | 0.0410 (16) | 0.0470 (18) | 0.0417 (17) | 0.0034 (13) | −0.0008 (13) | 0.0060 (14) |
C9B | 0.066 (2) | 0.0467 (18) | 0.0519 (19) | 0.0036 (15) | 0.0105 (16) | 0.0126 (15) |
C10B | 0.0578 (19) | 0.075 (2) | 0.0464 (18) | −0.0013 (17) | 0.0103 (15) | 0.0194 (17) |
C11B | 0.0563 (19) | 0.061 (2) | 0.0467 (18) | 0.0014 (16) | 0.0058 (15) | 0.0109 (16) |
C12B | 0.0519 (18) | 0.075 (2) | 0.0514 (19) | 0.0094 (16) | 0.0110 (15) | 0.0068 (17) |
C13B | 0.108 (3) | 0.068 (2) | 0.059 (2) | −0.007 (2) | 0.007 (2) | 0.0196 (19) |
C14B | 0.0594 (19) | 0.054 (2) | 0.0373 (17) | 0.0196 (16) | 0.0139 (14) | 0.0080 (15) |
C15B | 0.068 (2) | 0.066 (2) | 0.0456 (18) | 0.0236 (18) | 0.0182 (15) | 0.0200 (17) |
C16B | 0.094 (3) | 0.064 (2) | 0.066 (2) | 0.031 (2) | 0.037 (2) | 0.0313 (19) |
C17B | 0.091 (3) | 0.065 (2) | 0.081 (3) | 0.004 (2) | 0.032 (2) | 0.008 (2) |
C18B | 0.084 (2) | 0.060 (2) | 0.057 (2) | −0.0027 (19) | 0.0094 (18) | 0.0035 (18) |
O1C | 0.137 (2) | 0.101 (2) | 0.0527 (16) | 0.0005 (18) | 0.0089 (16) | 0.0164 (15) |
O2C | 0.0931 (19) | 0.125 (2) | 0.0781 (18) | 0.0135 (17) | −0.0071 (14) | 0.0595 (17) |
O3C | 0.096 (2) | 0.115 (2) | 0.120 (2) | 0.0430 (17) | 0.0179 (19) | 0.073 (2) |
O4C | 0.106 (2) | 0.107 (2) | 0.092 (2) | 0.0338 (16) | 0.0391 (17) | 0.0221 (17) |
C1C | 0.067 (2) | 0.086 (3) | 0.051 (2) | −0.010 (2) | 0.0039 (18) | 0.022 (2) |
C2C | 0.0514 (18) | 0.071 (2) | 0.058 (2) | 0.0087 (16) | −0.0005 (16) | 0.0270 (18) |
C3C | 0.062 (2) | 0.080 (2) | 0.050 (2) | 0.0121 (18) | 0.0012 (16) | 0.0276 (18) |
C4C | 0.066 (2) | 0.068 (2) | 0.087 (3) | −0.0007 (19) | 0.019 (2) | 0.020 (2) |
O4D | 0.126 (3) | 0.128 (3) | 0.238 (4) | 0.065 (2) | 0.056 (3) | 0.097 (3) |
O3D | 0.132 (3) | 0.126 (3) | 0.097 (2) | 0.059 (2) | 0.045 (2) | 0.028 (2) |
O2D | 0.0934 (17) | 0.1016 (18) | 0.0466 (14) | 0.0296 (14) | 0.0123 (12) | 0.0163 (13) |
O1D | 0.0944 (18) | 0.0979 (19) | 0.0629 (16) | 0.0126 (16) | 0.0274 (14) | 0.0044 (14) |
C4D | 0.078 (3) | 0.089 (3) | 0.143 (5) | 0.017 (2) | 0.027 (3) | 0.061 (3) |
C3D | 0.060 (2) | 0.127 (4) | 0.098 (3) | −0.007 (2) | 0.005 (2) | 0.066 (3) |
C2D | 0.062 (2) | 0.104 (3) | 0.061 (2) | −0.015 (2) | 0.0060 (19) | 0.033 (2) |
C1D | 0.052 (2) | 0.081 (3) | 0.056 (2) | −0.0072 (18) | 0.0095 (17) | 0.018 (2) |
O1W | 0.119 (4) | 0.229 (7) | 0.123 (5) | 0.112 (5) | 0.043 (4) | 0.118 (5) |
S1A—C1A | 1.764 (3) | N2B—C12B | 1.452 (4) |
S1A—C3A | 1.811 (3) | N2B—C13B | 1.467 (4) |
O1A—C1A | 1.201 (3) | N3B—C18B | 1.341 (4) |
O2A—C2A | 1.210 (3) | N3B—C14B | 1.349 (4) |
O3A—C8A | 1.368 (3) | N3B—H3NB | 0.86 (3) |
O3A—C11A | 1.428 (3) | C2B—C3B | 1.519 (4) |
N1A—C2A | 1.362 (4) | C3B—C4B | 1.530 (4) |
N1A—C1A | 1.368 (4) | C3B—H3B | 0.9800 |
N1A—H1NA | 0.84 (3) | C4B—C5B | 1.503 (4) |
N2A—C14A | 1.336 (3) | C4B—H4B1 | 0.9700 |
N2A—C13A | 1.458 (4) | C4B—H4B2 | 0.9700 |
N2A—C12A | 1.469 (3) | C5B—C10B | 1.371 (4) |
N3A—C18A | 1.371 (4) | C5B—C6B | 1.372 (4) |
N3A—C14A | 1.374 (4) | C6B—C7B | 1.382 (4) |
N3A—H3NA | 0.87 (3) | C6B—H6B | 0.9300 |
C2A—C3A | 1.513 (4) | C7B—C8B | 1.380 (4) |
C3A—C4A | 1.533 (4) | C7B—H7B | 0.9300 |
C3A—H3A | 0.9800 | C8B—C9B | 1.354 (4) |
C4A—C5A | 1.502 (4) | C9B—C10B | 1.394 (4) |
C4A—H4A1 | 0.9700 | C9B—H9B | 0.9300 |
C4A—H4A2 | 0.9700 | C10B—H10B | 0.9300 |
C5A—C10A | 1.372 (4) | C11B—C12B | 1.510 (4) |
C5A—C6A | 1.398 (4) | C11B—H11C | 0.9700 |
C6A—C7A | 1.369 (4) | C11B—H11D | 0.9700 |
C6A—H6A | 0.9300 | C12B—H12C | 0.9700 |
C7A—C8A | 1.380 (4) | C12B—H12D | 0.9700 |
C7A—H7A | 0.9300 | C13B—H13D | 0.9600 |
C8A—C9A | 1.385 (4) | C13B—H13E | 0.9600 |
C9A—C10A | 1.385 (4) | C13B—H13F | 0.9600 |
C9A—H9A | 0.9300 | C14B—C15B | 1.401 (4) |
C10A—H10A | 0.9300 | C15B—C16B | 1.351 (4) |
C11A—C12A | 1.510 (4) | C15B—H15B | 0.9300 |
C11A—H11A | 0.9700 | C16B—C17B | 1.403 (5) |
C11A—H11B | 0.9700 | C16B—H16B | 0.9300 |
C12A—H12A | 0.9700 | C17B—C18B | 1.351 (4) |
C12A—H12B | 0.9700 | C17B—H17B | 0.9300 |
C13A—H13A | 0.9600 | C18B—H18B | 0.9300 |
C13A—H13B | 0.9600 | O1C—C1C | 1.228 (4) |
C13A—H13C | 0.9600 | O2C—C1C | 1.269 (4) |
C14A—C15A | 1.383 (4) | O3C—C4C | 1.265 (4) |
C15A—C16A | 1.380 (4) | O3C—H3OC | 0.87 (3) |
C15A—H15A | 0.9300 | O4C—C4C | 1.235 (4) |
C16A—C17A | 1.367 (5) | C1C—C2C | 1.495 (4) |
C16A—H16A | 0.9300 | C2C—C3C | 1.319 (4) |
C17A—C18A | 1.354 (5) | C2C—H2C | 0.9300 |
C17A—H17A | 0.9300 | C3C—C4C | 1.480 (5) |
C18A—H18A | 0.9300 | C3C—H3C | 0.9300 |
S1B—C1B | 1.763 (3) | O4D—C4D | 1.212 (4) |
S1B—C3B | 1.808 (3) | O3D—C4D | 1.304 (5) |
O1B—C1B | 1.203 (3) | O3D—H3OD | 0.85 (3) |
O2B—C2B | 1.198 (3) | O2D—C1D | 1.257 (4) |
O3B—C8B | 1.382 (3) | O1D—C1D | 1.258 (4) |
O3B—C11B | 1.420 (3) | C4D—C3D | 1.487 (6) |
N1B—C1B | 1.371 (4) | C3D—C2D | 1.320 (5) |
N1B—C2B | 1.374 (4) | C3D—H3D | 0.9300 |
N1B—H1NB | 0.85 (3) | C2D—C1D | 1.460 (5) |
N2B—C14B | 1.345 (4) | C2D—H2D | 0.9300 |
C1A—S1A—C3A | 93.03 (14) | N1B—C1B—S1B | 110.0 (2) |
C8A—O3A—C11A | 118.5 (2) | O2B—C2B—N1B | 124.1 (3) |
C2A—N1A—C1A | 118.3 (3) | O2B—C2B—C3B | 125.0 (3) |
C2A—N1A—H1NA | 120 (2) | N1B—C2B—C3B | 110.8 (3) |
C1A—N1A—H1NA | 120 (2) | C2B—C3B—C4B | 111.1 (2) |
C14A—N2A—C13A | 120.0 (3) | C2B—C3B—S1B | 106.99 (18) |
C14A—N2A—C12A | 122.1 (3) | C4B—C3B—S1B | 112.5 (2) |
C13A—N2A—C12A | 117.1 (2) | C2B—C3B—H3B | 108.7 |
C18A—N3A—C14A | 121.8 (3) | C4B—C3B—H3B | 108.7 |
C18A—N3A—H3NA | 109 (2) | S1B—C3B—H3B | 108.7 |
C14A—N3A—H3NA | 129 (2) | C5B—C4B—C3B | 114.3 (2) |
O1A—C1A—N1A | 125.3 (3) | C5B—C4B—H4B1 | 108.7 |
O1A—C1A—S1A | 124.5 (3) | C3B—C4B—H4B1 | 108.7 |
N1A—C1A—S1A | 110.2 (2) | C5B—C4B—H4B2 | 108.7 |
O2A—C2A—N1A | 124.5 (3) | C3B—C4B—H4B2 | 108.7 |
O2A—C2A—C3A | 123.2 (3) | H4B1—C4B—H4B2 | 107.6 |
N1A—C2A—C3A | 112.3 (3) | C10B—C5B—C6B | 116.7 (3) |
C2A—C3A—C4A | 110.6 (2) | C10B—C5B—C4B | 122.5 (3) |
C2A—C3A—S1A | 106.12 (19) | C6B—C5B—C4B | 120.8 (3) |
C4A—C3A—S1A | 112.7 (2) | C5B—C6B—C7B | 122.7 (3) |
C2A—C3A—H3A | 109.1 | C5B—C6B—H6B | 118.6 |
C4A—C3A—H3A | 109.1 | C7B—C6B—H6B | 118.6 |
S1A—C3A—H3A | 109.1 | C8B—C7B—C6B | 119.0 (3) |
C5A—C4A—C3A | 112.5 (2) | C8B—C7B—H7B | 120.5 |
C5A—C4A—H4A1 | 109.1 | C6B—C7B—H7B | 120.5 |
C3A—C4A—H4A1 | 109.1 | C9B—C8B—C7B | 119.9 (3) |
C5A—C4A—H4A2 | 109.1 | C9B—C8B—O3B | 117.0 (3) |
C3A—C4A—H4A2 | 109.1 | C7B—C8B—O3B | 123.1 (3) |
H4A1—C4A—H4A2 | 107.8 | C8B—C9B—C10B | 119.7 (3) |
C10A—C5A—C6A | 117.9 (3) | C8B—C9B—H9B | 120.1 |
C10A—C5A—C4A | 121.7 (3) | C10B—C9B—H9B | 120.1 |
C6A—C5A—C4A | 120.3 (3) | C5B—C10B—C9B | 122.0 (3) |
C7A—C6A—C5A | 120.8 (3) | C5B—C10B—H10B | 119.0 |
C7A—C6A—H6A | 119.6 | C9B—C10B—H10B | 119.0 |
C5A—C6A—H6A | 119.6 | O3B—C11B—C12B | 107.9 (2) |
C6A—C7A—C8A | 120.4 (3) | O3B—C11B—H11C | 110.1 |
C6A—C7A—H7A | 119.8 | C12B—C11B—H11C | 110.1 |
C8A—C7A—H7A | 119.8 | O3B—C11B—H11D | 110.1 |
O3A—C8A—C7A | 115.2 (2) | C12B—C11B—H11D | 110.1 |
O3A—C8A—C9A | 124.8 (3) | H11C—C11B—H11D | 108.4 |
C7A—C8A—C9A | 120.0 (3) | N2B—C12B—C11B | 113.9 (2) |
C8A—C9A—C10A | 118.7 (3) | N2B—C12B—H12C | 108.8 |
C8A—C9A—H9A | 120.6 | C11B—C12B—H12C | 108.8 |
C10A—C9A—H9A | 120.6 | N2B—C12B—H12D | 108.8 |
C5A—C10A—C9A | 122.2 (3) | C11B—C12B—H12D | 108.8 |
C5A—C10A—H10A | 118.9 | H12C—C12B—H12D | 107.7 |
C9A—C10A—H10A | 118.9 | N2B—C13B—H13D | 109.5 |
O3A—C11A—C12A | 106.2 (2) | N2B—C13B—H13E | 109.5 |
O3A—C11A—H11A | 110.5 | H13D—C13B—H13E | 109.5 |
C12A—C11A—H11A | 110.5 | N2B—C13B—H13F | 109.5 |
O3A—C11A—H11B | 110.5 | H13D—C13B—H13F | 109.5 |
C12A—C11A—H11B | 110.5 | H13E—C13B—H13F | 109.5 |
H11A—C11A—H11B | 108.7 | N2B—C14B—N3B | 118.7 (3) |
N2A—C12A—C11A | 111.9 (2) | N2B—C14B—C15B | 124.3 (3) |
N2A—C12A—H12A | 109.2 | N3B—C14B—C15B | 117.0 (3) |
C11A—C12A—H12A | 109.2 | C16B—C15B—C14B | 119.7 (3) |
N2A—C12A—H12B | 109.2 | C16B—C15B—H15B | 120.1 |
C11A—C12A—H12B | 109.2 | C14B—C15B—H15B | 120.1 |
H12A—C12A—H12B | 107.9 | C15B—C16B—C17B | 121.0 (3) |
N2A—C13A—H13A | 109.5 | C15B—C16B—H16B | 119.5 |
N2A—C13A—H13B | 109.5 | C17B—C16B—H16B | 119.5 |
H13A—C13A—H13B | 109.5 | C18B—C17B—C16B | 118.3 (3) |
N2A—C13A—H13C | 109.5 | C18B—C17B—H17B | 120.8 |
H13A—C13A—H13C | 109.5 | C16B—C17B—H17B | 120.8 |
H13B—C13A—H13C | 109.5 | N3B—C18B—C17B | 119.8 (3) |
N2A—C14A—N3A | 120.7 (3) | N3B—C18B—H18B | 120.1 |
N2A—C14A—C15A | 122.5 (3) | C17B—C18B—H18B | 120.1 |
N3A—C14A—C15A | 116.8 (3) | C4C—O3C—H3OC | 118 (3) |
C16A—C15A—C14A | 121.0 (3) | O1C—C1C—O2C | 124.6 (3) |
C16A—C15A—H15A | 119.5 | O1C—C1C—C2C | 116.6 (4) |
C14A—C15A—H15A | 119.5 | O2C—C1C—C2C | 118.7 (3) |
C17A—C16A—C15A | 120.8 (3) | C3C—C2C—C1C | 130.0 (3) |
C17A—C16A—H16A | 119.6 | C3C—C2C—H2C | 115.0 |
C15A—C16A—H16A | 119.6 | C1C—C2C—H2C | 115.0 |
C18A—C17A—C16A | 118.6 (3) | C2C—C3C—C4C | 131.0 (3) |
C18A—C17A—H17A | 120.7 | C2C—C3C—H3C | 114.5 |
C16A—C17A—H17A | 120.7 | C4C—C3C—H3C | 114.5 |
C17A—C18A—N3A | 120.9 (3) | O4C—C4C—O3C | 123.2 (4) |
C17A—C18A—H18A | 119.5 | O4C—C4C—C3C | 116.0 (4) |
N3A—C18A—H18A | 119.5 | O3C—C4C—C3C | 120.8 (3) |
C1B—S1B—C3B | 93.02 (14) | C4D—O3D—H3OD | 110 (3) |
C8B—O3B—C11B | 117.1 (2) | O4D—C4D—O3D | 119.8 (5) |
C1B—N1B—C2B | 119.0 (3) | O4D—C4D—C3D | 121.8 (5) |
C1B—N1B—H1NB | 114 (2) | O3D—C4D—C3D | 118.4 (4) |
C2B—N1B—H1NB | 127 (2) | C2D—C3D—C4D | 132.6 (4) |
C14B—N2B—C12B | 123.0 (3) | C2D—C3D—H3D | 113.7 |
C14B—N2B—C13B | 121.8 (3) | C4D—C3D—H3D | 113.7 |
C12B—N2B—C13B | 115.2 (3) | C3D—C2D—C1D | 130.6 (4) |
C18B—N3B—C14B | 124.2 (3) | C3D—C2D—H2D | 114.7 |
C18B—N3B—H3NB | 109 (2) | C1D—C2D—H2D | 114.7 |
C14B—N3B—H3NB | 126 (2) | O2D—C1D—O1D | 122.7 (3) |
O1B—C1B—N1B | 125.3 (3) | O2D—C1D—C2D | 120.4 (3) |
O1B—C1B—S1B | 124.7 (3) | O1D—C1D—C2D | 116.9 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3C—H3OC···O2C | 0.87 (3) | 1.58 (3) | 2.420 (4) | 164 (5) |
N1A—H1NA···O4C | 0.84 (3) | 1.94 (3) | 2.767 (4) | 167 (3) |
N1B—H1NB···O1D | 0.85 (3) | 1.95 (3) | 2.795 (3) | 176 (3) |
O3D—H3OD···O2D | 0.85 (3) | 1.62 (3) | 2.452 (3) | 167 (5) |
N3B—H3NB···O1Ci | 0.86 (3) | 1.88 (3) | 2.724 (3) | 168 (3) |
N3A—H3NA···O1Dii | 0.87 (3) | 2.02 (3) | 2.858 (4) | 161 (3) |
C3B—H3B···O2Aiii | 0.98 | 2.45 | 3.289 (4) | 144 |
C6B—H6B···O2Aiii | 0.93 | 2.33 | 3.187 (4) | 153 |
C15A—H15A···O1Wiii | 0.93 | 2.30 | 3.189 (8) | 159 |
Symmetry codes: (i) x, y−1, z−1; (ii) −x+1, −y, −z+1; (iii) −x+1, −y+1, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C18H20N3O3S+·C4H3O4−·0.25H2O |
Mr | 478.01 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 298 |
a, b, c (Å) | 9.3145 (8), 12.3555 (10), 20.8280 (17) |
α, β, γ (°) | 105.475 (2), 96.330 (3), 93.276 (2) |
V (Å3) | 2286.6 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.19 |
Crystal size (mm) | 0.52 × 0.12 × 0.11 |
Data collection | |
Diffractometer | Bruker Model? CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2001) |
Tmin, Tmax | 0.90, 0.98 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19294, 9856, 5102 |
Rint | 0.058 |
(sin θ/λ)max (Å−1) | 0.662 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.063, 0.154, 0.95 |
No. of reflections | 9856 |
No. of parameters | 624 |
No. of restraints | 6 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.43, −0.26 |
Computer programs: SMART-NT (Bruker, 2001), SAINT-NT (Bruker, 2001), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL-NT (Bruker, 2001) and PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
O3C—H3OC···O2C | 0.87 (3) | 1.58 (3) | 2.420 (4) | 164 (5) |
N1A—H1NA···O4C | 0.84 (3) | 1.94 (3) | 2.767 (4) | 167 (3) |
N1B—H1NB···O1D | 0.85 (3) | 1.95 (3) | 2.795 (3) | 176 (3) |
O3D—H3OD···O2D | 0.85 (3) | 1.62 (3) | 2.452 (3) | 167 (5) |
N3B—H3NB···O1Ci | 0.86 (3) | 1.88 (3) | 2.724 (3) | 168 (3) |
N3A—H3NA···O1Dii | 0.87 (3) | 2.02 (3) | 2.858 (4) | 161 (3) |
C3B—H3B···O2Aiii | 0.98 | 2.45 | 3.289 (4) | 144 |
C6B—H6B···O2Aiii | 0.93 | 2.33 | 3.187 (4) | 153 |
C15A—H15A···O1Wiii | 0.93 | 2.30 | 3.189 (8) | 159 |
Symmetry codes: (i) x, y−1, z−1; (ii) −x+1, −y, −z+1; (iii) −x+1, −y+1, −z+1. |
Parameter | Za in (II) | Zb in (II) | Zc in (I) |
S1—C1 | 1.764 (3) | 1.763 (3) | |
C8—O3—C11—C12 | 179.2 | 20.5 | 177.9 |
C13—N2—C14—N3 | -178 | 7.7 | 1.5 |
Several drugs in the thiazolidinedione group (see scheme) have been reported to present antidiabetic effects, such troglitazone, pioglitazone and rosiglitazone. Probably as a consequence of having appeared on the market previously, troglitazone and pioglitazone have already been the subject of a thorough structural characterization of the many polymorphic or pseudo-polymorphic forms known, and a number of entries can be found in the Cambridge Structural Database (CSD, version of November 2006 with 2007 updates; Allen, 2002). Rosiglitazone (either as such or in its protonated version, hereinafter H-rosiglitazone) presents instead an interesting challenge from a structural point of view: two main forms with similar therapeutic properties are on the pharmaceutical market to date, namely the hydrochloride monohydrate, (I), and the maleate, nebulously described in different patents (for example, Blackler et al., 1999a,b; Blackler, Browne et al., 2000; Blackler, Giles et al., 2000; Blackler, Giles & Sasse, 2000; Giles et al., 1999; Lynch et al., 1999) in a variety of hydration states (.nH2O, where n ranges from zero to 0.6) and with significant differences in their X-ray powder diffraction diagrams. So far, only the hydrochloride monohydrate, (I), has been structurally characterized (Cantello et al., 1994) in an enantiomerically pure sample of biochemical origin.
In the present work, we try to fill this gap in the literature, reporting the crystal and molecular structure of the title maleate 0.25-hydrate, (II), hitherto structurally uncharacterized. Our results show that compound (II), as formed by crystallization from ethyl acetate of a commercial sample of synthetic origin, is a racemate, in space group P21/n, composed of two independent units (hereinafter Za and Zb) of the protonated H-rosiglitazone cation (±)-5-(4-{2-[methyl(2-pyridyl)amino]-ethoxy}benzyl)thiazolidine-2,4-dione+, with the charge balance provided by two independent hydrogenmaleate anions (hereinafter Hma-), and one-half of a hydration water molecule, thus giving a minimum formula of C18H20N3O3S+·C4H3O4-·0.25H2O. As in (I), both Z units in (II) are cationic, bearing one H atom at N3. In the former structure, charge balance is achieved through the presence of a Cl- counterion, whereas in (II), the counterions are two hydrogenmaleate ions Hma-.
A general view of the full asymmetric unit of (II) (Fig. 1) shows most of the key points. Firstly, it is apparent that both independent cations (Za and Zb) in (II) are geometrically very similar both to one another (Table 1) and to the cation in (I), despite the presence in (I) of just a single enantiomer. The main overall differences reside in the C8—O3—C11—C12 torsion angle at the ethoxy site (179.2° for Za, 20.5° for Zb and 177.9° for Zc) [Zc is the cation in (I)] and the C13—N2—C14—N3 torsion angle at the methylpyridylamino site (-178° for Za, 7.7° for Zb and 1.5° for Zc), which result in the terminal groups being oriented in different directions. Fig. 2 clarifies these differences through the least-squares fitting of individual moieties onto each other. It is apparent that the conformation of the cation Zc in (I) is somewhere between those of Za and Zb in (II)
The unique acidic H atoms in both anions make two rather strong almost linear intramolecular O···H—O bonds (Table 2) defining a closed ring each and giving the molecule the appearance of a `crab'. This is rather common in isolated Hma- units: a search of the CSD gave a total of 115 reported cases of uncoordinated singly protonated Hma- anions, of which 113 showed this arrangement, while the H-atom locations in the remaining two structures were uncertain. Although unusually short for conventional O···H—O interactions, the H···O distances in (II) (1.576 and 1.617 Å) lie in the longest quartile of the reported H···O range for uncoordinated Hma- units (1.809–1.1223 Å). Thus, the intramolecular maleate hydrogen bonds found in (II) can be typified as comparatively weak when contrasted with their counterparts in the literature, in spite of their strength when evaluated in absolute terms.
It is interesting to compare the packing schemes of (I) and (II). The former presents, as characteristic features, a unique enantiomer and a counterion which can only behave as a hydrogen-bond acceptor, whereas the latter is a racemate counterbalanced by a flexible hydrogen-bonding donor/acceptor. Fig. 3 shows schematically the way in which the hydrochloride (I) packs, with the independent components defining a two-dimensional structure, tightly bound in a plane and loosely connected in the perpendicular direction by much weaker interactions. Structure (II) instead presents a much more complex disposition: the two independent Za and Zb molecules are tightly related to their counterparts at (1 - x, -y, 1 - z) through hydrogen-bonding interactions mediated by N—H groups in the molecules and O—H groups in the Hma- anions (Fig. 4 and Table 2). Thus, a kind of tetramer builds up with two representatives of each hand, which only leaves available for inter-tetrameric interaction two out of the four N3—H3N groups, N3B—H3NB and its symmetric image through the tetramer centring. The remaining two, in turn, are devoted to construction of the tetramer via intra-tetrameric hydrogen bonds (Table 2). Thus, the external linkage is achieved at both sides of the rod-like group, defining a zigzag chain running along [011]. Interchain interactions, as in the case of (I), involve the much weaker C—H···O bonds (Table 2).
The (depleted) solvent water molecule attaches via hydrogen bonding (only inferred by the O···O distances and their relative disposition) at the extreme end of the tetramers, occupying a sort of capping position (Fig 1). Its occupation factor of 0.5 is a result of the position of the solvate in the `exclusion zone' of a centre of symmetry in the structure: the solvate lies ca 2.6 Å away from its own symmetry-related image and accordingly they are mutually exclusive, leading to a maximum possible presence for each one of 1/2, precisely as deduced from the refinement.
Comparison of the (calculated) X-ray powder diffraction of (II) with the experimental diagrams presented in the different patents in the literature suggests a best match with that in WO 9931093 (Lynch et al., 1999). The water fraction, however, is slightly lower (0.25 mol in the present form versus 0.40 mol in the patent), a fact which should not surprise since the result from the Karl Fischer titration employed in the patent characterization may include some surface-adsorbed water, in contrast with the purely crystallographic water reported here.