Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801016622/ob6078sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536801016622/ob6078Isup2.hkl |
CCDC reference: 176014
The synthesis of the title compound, (I), has been described by Pirotte, de Tullio et al. (1993). Crystals of (I) were obtained by slow evaporation of a methanol solution.
All H atoms (with the exception of the nitrogen-bound atoms H4 and H11, and the water H atoms H31 and H32) were included in the refinement as riding, with isotropic displacement parameters fixed at 1.2Ueq of the parent atom (1.5Ueq for methyl H atoms). Atoms H4, H11, H31 and H32 were refined isotropically, their displacement parameters being fixed at 1.2Ueq of the N– or O-bound atom. H32 was nevertheless kept fixed in the last cycles of least-squares refinement. The large value (1/4) of wR2 at the end of the refinement could be related with a slight disorder of the N-alkylsulfonylguanidine moiety. Some of its atoms exhibit indeed rather large values of anisotropic displacement parameters. Various data collections undertaken with Mo Kα radiation on different samples mounted on the Stoe four-circle diffractometer and also on a MAR345 image-plate diffractometer yielded similar results.
Data collection: DIF4 (Stoe & Cie, 1987); cell refinement: DIF4; data reduction: REDU4 (Stoe & Cie, 1987); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-III (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97.
Fig. 1. The molecular structure of (I) with the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level. |
C11H16N4O2S·H2O | Dx = 1.306 Mg m−3 |
Mr = 286.35 | Cu Kα radiation, λ = 1.54180 Å |
Trigonal, R3 | Cell parameters from 30 reflections |
a = 26.198 (5) Å | θ = 20.7–40.7° |
c = 11.024 (7) Å | µ = 2.08 mm−1 |
V = 6552 (4) Å3 | T = 293 K |
Z = 18 | Prism, colourless |
F(000) = 2736 | 0.57 × 0.38 × 0.34 mm |
Stoe-Siemens AED four-circle diffractometer | 1429 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.049 |
Graphite monochromator | θmax = 60.0°, θmin = 3.4° |
ω scans | h = −29→25 |
Absorption correction: ψ scan (EMPIR; Stoe & Cie, 1987) | k = 0→29 |
Tmin = 0.351, Tmax = 0.493 | l = −12→12 |
6653 measured reflections | 2 standard reflections every 60 min |
2166 independent reflections | intensity decay: 5% |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: H atoms were placed at standard calculated positions, except atoms H(N4), H(N11) and H(water), which were obtained from difference map. |
R[F2 > 2σ(F2)] = 0.077 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.251 | w = 1/[σ2(Fo2) + (0.1779P)2 + 0.4536P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max < 0.001 |
2166 reflections | Δρmax = 0.44 e Å−3 |
185 parameters | Δρmin = −0.27 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.00026 (11) |
C11H16N4O2S·H2O | Z = 18 |
Mr = 286.35 | Cu Kα radiation |
Trigonal, R3 | µ = 2.08 mm−1 |
a = 26.198 (5) Å | T = 293 K |
c = 11.024 (7) Å | 0.57 × 0.38 × 0.34 mm |
V = 6552 (4) Å3 |
Stoe-Siemens AED four-circle diffractometer | 1429 reflections with I > 2σ(I) |
Absorption correction: ψ scan (EMPIR; Stoe & Cie, 1987) | Rint = 0.049 |
Tmin = 0.351, Tmax = 0.493 | θmax = 60.0° |
6653 measured reflections | 2 standard reflections every 60 min |
2166 independent reflections | intensity decay: 5% |
R[F2 > 2σ(F2)] = 0.077 | 0 restraints |
wR(F2) = 0.251 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.05 | Δρmax = 0.44 e Å−3 |
2166 reflections | Δρmin = −0.27 e Å−3 |
185 parameters |
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 | 0.54453 (5) | 0.03102 (6) | 0.24676 (11) | 0.0792 (6) | |
O1 | 0.5508 (2) | −0.0180 (2) | 0.2836 (6) | 0.164 (3) | |
O2 | 0.5676 (2) | 0.0532 (3) | 0.1332 (4) | 0.171 (3) | |
N2 | 0.57457 (19) | 0.0802 (2) | 0.3424 (4) | 0.0950 (14) | |
C3 | 0.5445 (2) | 0.0903 (2) | 0.4269 (4) | 0.0764 (13) | |
N4 | 0.4854 (2) | 0.0640 (2) | 0.4300 (4) | 0.0856 (14) | |
H4 | 0.474 (3) | 0.079 (3) | 0.465 (6) | 0.103* | |
C5 | 0.4484 (2) | 0.0277 (2) | 0.3420 (4) | 0.0717 (12) | |
C6 | 0.3878 (2) | 0.0073 (2) | 0.3426 (5) | 0.0813 (14) | |
H6 | 0.3711 | 0.0183 | 0.4044 | 0.098* | |
C7 | 0.3543 (2) | −0.0281 (3) | 0.2535 (5) | 0.0876 (15) | |
H7 | 0.3141 | −0.0414 | 0.2571 | 0.105* | |
N8 | 0.37385 (19) | −0.0461 (2) | 0.1584 (4) | 0.0907 (13) | |
C9 | 0.4319 (2) | −0.0264 (2) | 0.1572 (5) | 0.0832 (14) | |
H9 | 0.4474 | −0.0370 | 0.0924 | 0.100* | |
C10 | 0.47038 (19) | 0.0090 (2) | 0.2478 (4) | 0.0655 (12) | |
N11 | 0.5734 (2) | 0.1293 (2) | 0.5140 (4) | 0.0945 (14) | |
H11 | 0.543 (3) | 0.130 (3) | 0.569 (6) | 0.113* | |
C12 | 0.6380 (2) | 0.1602 (3) | 0.5307 (6) | 0.109 (2) | |
H12 | 0.6505 | 0.1319 | 0.5090 | 0.131* | |
C13 | 0.6664 (5) | 0.2076 (6) | 0.4488 (10) | 0.219 (6) | |
H13A | 0.6557 | 0.1933 | 0.3673 | 0.329* | |
H13B | 0.7083 | 0.2256 | 0.4583 | 0.329* | |
H13C | 0.6545 | 0.2362 | 0.4650 | 0.329* | |
C14 | 0.6517 (3) | 0.1736 (4) | 0.6632 (7) | 0.137 (3) | |
H14 | 0.6267 | 0.1381 | 0.7108 | 0.164* | |
C15 | 0.7165 (4) | 0.1937 (6) | 0.6889 (8) | 0.192 (5) | |
H15A | 0.7258 | 0.1652 | 0.6574 | 0.288* | |
H15B | 0.7233 | 0.1975 | 0.7749 | 0.288* | |
H15C | 0.7411 | 0.2311 | 0.6507 | 0.288* | |
C16 | 0.6377 (4) | 0.2237 (5) | 0.6992 (9) | 0.188 (5) | |
H16A | 0.6615 | 0.2452 | 0.7675 | 0.283* | |
H16B | 0.5968 | 0.2062 | 0.7201 | 0.283* | |
H16C | 0.6464 | 0.2500 | 0.6318 | 0.283* | |
O3 | 0.5306 (2) | −0.1266 (2) | 0.3735 (4) | 0.1110 (15) | |
H31 | 0.553 (3) | −0.101 (3) | 0.320 (7) | 0.133* | |
H32 | 0.5460 | −0.1360 | 0.4075 | 0.133* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0728 (9) | 0.0991 (10) | 0.0752 (9) | 0.0500 (7) | 0.0040 (6) | −0.0165 (6) |
O1 | 0.129 (4) | 0.119 (3) | 0.288 (8) | 0.096 (3) | −0.040 (4) | −0.045 (4) |
O2 | 0.085 (3) | 0.273 (7) | 0.073 (3) | 0.029 (4) | 0.006 (2) | −0.011 (3) |
N2 | 0.070 (3) | 0.123 (4) | 0.092 (3) | 0.049 (3) | 0.000 (2) | −0.031 (3) |
C3 | 0.077 (3) | 0.090 (3) | 0.073 (3) | 0.050 (3) | −0.003 (2) | −0.012 (3) |
N4 | 0.071 (3) | 0.104 (3) | 0.084 (3) | 0.045 (2) | 0.010 (2) | −0.023 (2) |
C5 | 0.067 (3) | 0.084 (3) | 0.069 (3) | 0.041 (2) | 0.003 (2) | −0.003 (2) |
C6 | 0.068 (3) | 0.095 (3) | 0.083 (3) | 0.043 (3) | 0.010 (3) | 0.000 (3) |
C7 | 0.064 (3) | 0.101 (4) | 0.095 (4) | 0.039 (3) | 0.002 (3) | 0.010 (3) |
N8 | 0.071 (3) | 0.111 (3) | 0.083 (3) | 0.040 (3) | −0.010 (2) | 0.000 (2) |
C9 | 0.083 (3) | 0.096 (4) | 0.069 (3) | 0.044 (3) | −0.002 (3) | −0.006 (3) |
C10 | 0.066 (3) | 0.073 (3) | 0.061 (3) | 0.038 (2) | 0.002 (2) | 0.000 (2) |
N11 | 0.078 (3) | 0.116 (4) | 0.090 (3) | 0.050 (3) | −0.007 (2) | −0.035 (3) |
C12 | 0.077 (4) | 0.125 (5) | 0.102 (4) | 0.033 (4) | 0.002 (3) | −0.039 (4) |
C13 | 0.138 (8) | 0.239 (13) | 0.195 (11) | 0.030 (8) | −0.020 (8) | 0.061 (10) |
C14 | 0.093 (5) | 0.164 (7) | 0.119 (6) | 0.039 (5) | −0.019 (4) | −0.008 (5) |
C15 | 0.127 (7) | 0.266 (14) | 0.160 (9) | 0.082 (8) | −0.032 (6) | −0.019 (8) |
C16 | 0.138 (7) | 0.238 (12) | 0.181 (9) | 0.088 (8) | −0.015 (6) | −0.115 (9) |
O3 | 0.126 (4) | 0.159 (4) | 0.093 (3) | 0.105 (3) | 0.021 (2) | 0.008 (3) |
S1—O2 | 1.386 (5) | N11—H11 | 1.00 (6) |
S1—O1 | 1.433 (5) | C12—C13 | 1.410 (12) |
S1—N2 | 1.542 (4) | C12—C14 | 1.504 (10) |
S1—C10 | 1.728 (4) | C12—H12 | 0.9800 |
N2—C3 | 1.330 (6) | C13—H13A | 0.9600 |
C3—N11 | 1.329 (6) | C13—H13B | 0.9600 |
C3—N4 | 1.343 (6) | C13—H13C | 0.9600 |
N4—C5 | 1.365 (6) | C14—C15 | 1.531 (11) |
N4—H4 | 0.72 (6) | C14—C16 | 1.579 (12) |
C5—C10 | 1.388 (6) | C14—H14 | 0.9800 |
C5—C6 | 1.399 (7) | C15—H15A | 0.9600 |
C6—C7 | 1.335 (7) | C15—H15B | 0.9600 |
C6—H6 | 0.9300 | C15—H15C | 0.9600 |
C7—N8 | 1.351 (7) | C16—H16A | 0.9600 |
C7—H7 | 0.9300 | C16—H16B | 0.9600 |
N8—C9 | 1.340 (7) | C16—H16C | 0.9600 |
C9—C10 | 1.392 (6) | O3—H31 | 0.86 (7) |
C9—H9 | 0.9300 | O3—H32 | 0.68 |
N11—C12 | 1.476 (7) | ||
O2—S1—O1 | 114.3 (4) | C13—C12—N11 | 111.0 (7) |
O2—S1—N2 | 109.5 (3) | C13—C12—C14 | 117.2 (8) |
O1—S1—N2 | 108.4 (3) | N11—C12—C14 | 108.9 (5) |
O2—S1—C10 | 109.1 (3) | C13—C12—H12 | 106.4 |
O1—S1—C10 | 108.2 (3) | N11—C12—H12 | 106.4 |
N2—S1—C10 | 107.0 (2) | C14—C12—H12 | 106.4 |
C3—N2—S1 | 122.7 (4) | C12—C13—H13A | 109.5 |
N11—C3—N2 | 119.5 (5) | C12—C13—H13B | 109.5 |
N11—C3—N4 | 116.4 (4) | H13A—C13—H13B | 109.5 |
N2—C3—N4 | 124.1 (5) | C12—C13—H13C | 109.5 |
C3—N4—C5 | 125.1 (4) | H13A—C13—H13C | 109.5 |
C3—N4—H4 | 115 (5) | H13B—C13—H13C | 109.5 |
C5—N4—H4 | 115 (5) | C12—C14—C15 | 110.8 (7) |
N4—C5—C10 | 120.1 (4) | C12—C14—C16 | 108.0 (7) |
N4—C5—C6 | 122.5 (4) | C15—C14—C16 | 110.2 (8) |
C10—C5—C6 | 117.4 (5) | C12—C14—H14 | 109.3 |
C7—C6—C5 | 119.3 (5) | C15—C14—H14 | 109.3 |
C7—C6—H6 | 120.4 | C16—C14—H14 | 109.3 |
C5—C6—H6 | 120.4 | C14—C15—H15A | 109.5 |
C6—C7—N8 | 125.5 (5) | C14—C15—H15B | 109.5 |
C6—C7—H7 | 117.3 | H15A—C15—H15B | 109.5 |
N8—C7—H7 | 117.3 | C14—C15—H15C | 109.5 |
C9—N8—C7 | 115.4 (5) | H15A—C15—H15C | 109.5 |
N8—C9—C10 | 123.6 (5) | H15B—C15—H15C | 109.5 |
N8—C9—H9 | 118.2 | C14—C16—H16A | 109.5 |
C10—C9—H9 | 118.2 | C14—C16—H16B | 109.5 |
C5—C10—C9 | 118.8 (4) | H16A—C16—H16B | 109.5 |
C5—C10—S1 | 118.8 (4) | C14—C16—H16C | 109.5 |
C9—C10—S1 | 122.3 (4) | H16A—C16—H16C | 109.5 |
C3—N11—C12 | 124.6 (5) | H16B—C16—H16C | 109.5 |
C3—N11—H11 | 108 (4) | H31—O3—H32 | 111 |
C12—N11—H11 | 128 (4) | ||
O2—S1—N2—C3 | 133.6 (5) | C6—C5—C10—S1 | −177.7 (4) |
O1—S1—N2—C3 | −101.2 (5) | N8—C9—C10—C5 | −3.3 (8) |
C10—S1—N2—C3 | 15.4 (6) | N8—C9—C10—S1 | 177.1 (4) |
S1—N2—C3—N11 | 173.2 (5) | O2—S1—C10—C5 | −130.8 (5) |
S1—N2—C3—N4 | −7.9 (8) | O1—S1—C10—C5 | 104.3 (5) |
N11—C3—N4—C5 | 172.6 (5) | N2—S1—C10—C5 | −12.4 (5) |
N2—C3—N4—C5 | −6.3 (9) | O2—S1—C10—C9 | 48.8 (6) |
C3—N4—C5—C10 | 8.8 (8) | O1—S1—C10—C9 | −76.1 (5) |
C3—N4—C5—C6 | −171.9 (5) | N2—S1—C10—C9 | 167.3 (4) |
N4—C5—C6—C7 | 179.9 (5) | N2—C3—N11—C12 | −4.9 (9) |
C10—C5—C6—C7 | −0.7 (8) | N4—C3—N11—C12 | 176.1 (6) |
C5—C6—C7—N8 | −1.1 (9) | C3—N11—C12—C13 | 79.4 (10) |
C6—C7—N8—C9 | 0.7 (8) | C3—N11—C12—C14 | −150.1 (7) |
C7—N8—C9—C10 | 1.6 (8) | C13—C12—C14—C15 | −64.8 (13) |
N4—C5—C10—C9 | −177.9 (5) | N11—C12—C14—C15 | 168.2 (8) |
C6—C5—C10—C9 | 2.7 (7) | C13—C12—C14—C16 | 56.0 (11) |
N4—C5—C10—S1 | 1.7 (7) | N11—C12—C14—C16 | −71.0 (8) |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···O3i | 0.72 (6) | 2.21 (6) | 2.872 (6) | 154 (6) |
N11—H11···O3i | 1.00 (6) | 1.99 (6) | 2.961 (6) | 161 (5) |
O3—H31···N8ii | 0.86 (7) | 2.27 (7) | 2.997 (6) | 141 (7) |
O3—H31···O1 | 0.86 (7) | 2.24 (8) | 2.801 (7) | 122 (6) |
O3—H32···O2iii | 0.68 | 2.12 | 2.771 (6) | 161 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) y+2/3, −x+y+1/3, −z+1/3; (iii) −y+2/3, x−y−2/3, z+1/3. |
Experimental details
Crystal data | |
Chemical formula | C11H16N4O2S·H2O |
Mr | 286.35 |
Crystal system, space group | Trigonal, R3 |
Temperature (K) | 293 |
a, c (Å) | 26.198 (5), 11.024 (7) |
V (Å3) | 6552 (4) |
Z | 18 |
Radiation type | Cu Kα |
µ (mm−1) | 2.08 |
Crystal size (mm) | 0.57 × 0.38 × 0.34 |
Data collection | |
Diffractometer | Stoe-Siemens AED four-circle diffractometer |
Absorption correction | ψ scan (EMPIR; Stoe & Cie, 1987) |
Tmin, Tmax | 0.351, 0.493 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6653, 2166, 1429 |
Rint | 0.049 |
θmax (°) | 60.0 |
(sin θ/λ)max (Å−1) | 0.562 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.077, 0.251, 1.05 |
No. of reflections | 2166 |
No. of parameters | 185 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.44, −0.27 |
Computer programs: DIF4 (Stoe & Cie, 1987), DIF4, REDU4 (Stoe & Cie, 1987), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-III (Burnett & Johnson, 1996), SHELXL97.
S1—O2 | 1.386 (5) | C3—N11 | 1.329 (6) |
S1—O1 | 1.433 (5) | C3—N4 | 1.343 (6) |
S1—N2 | 1.542 (4) | N11—C12 | 1.476 (7) |
N2—C3 | 1.330 (6) | ||
N2—S1—C10 | 107.0 (2) | N2—C3—N4 | 124.1 (5) |
C3—N2—S1 | 122.7 (4) | C3—N4—C5 | 125.1 (4) |
N11—C3—N2 | 119.5 (5) | C3—N11—C12 | 124.6 (5) |
N11—C3—N4 | 116.4 (4) | ||
C10—S1—N2—C3 | 15.4 (6) | N2—S1—C10—C5 | −12.4 (5) |
S1—N2—C3—N11 | 173.2 (5) | N2—C3—N11—C12 | −4.9 (9) |
S1—N2—C3—N4 | −7.9 (8) | C3—N11—C12—C13 | 79.4 (10) |
N11—C3—N4—C5 | 172.6 (5) | C3—N11—C12—C14 | −150.1 (7) |
N2—C3—N4—C5 | −6.3 (9) | N11—C12—C14—C15 | 168.2 (8) |
C3—N4—C5—C10 | 8.8 (8) | N11—C12—C14—C16 | −71.0 (8) |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···O3i | 0.72 (6) | 2.21 (6) | 2.872 (6) | 154 (6) |
N11—H11···O3i | 1.00 (6) | 1.99 (6) | 2.961 (6) | 161 (5) |
O3—H31···N8ii | 0.86 (7) | 2.27 (7) | 2.997 (6) | 141 (7) |
O3—H31···O1 | 0.86 (7) | 2.24 (8) | 2.801 (7) | 122 (6) |
O3—H32···O2iii | 0.68 | 2.12 | 2.771 (6) | 161 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) y+2/3, −x+y+1/3, −z+1/3; (iii) −y+2/3, x−y−2/3, z+1/3. |
The crystal structure of the title compound, (I), was determined in order to confirm that the best representative of pancreatic B-cell selective KATP channel openers belonging to the class of pyridothiadiazine dioxides was structurally related to both diazoxide (a benzothiadiazine dioxide KATP channel opener; Bandoli & Nicolini, 1977) and pinacidil (a pyridylalkylcyanoguanidine KATP channel opener; Pirotte, Dupont et al., 1993).
The crystal packing of (I) is dominated by four hydrogen bonds (Table 2). The water molecule is an acceptor in two N—H···O bonds and a donor in O—H···N(pyridinic) and O—H···O(sulfoxide) bonds. This scheme confirms the 4H-tautomeric form as N4 is engaged in an hydrogen bond, whereas N2 is not included in any close intermolecular contact. The same orientation of N4—H and N11—H is similar to that of the two guanidic NH groups observed in pinacidil.