Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270112043405/yf3020sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270112043405/yf3020Isup2.hkl | |
Chemical Markup Language (CML) file https://doi.org/10.1107/S0108270112043405/yf3020Isup3.cml |
CCDC reference: 914655
For related literature, see: Allen (2002); Amidon et al. (1995); Caira et al. (2003); Fossheim (1986); Goldmann & Stoltefuss (1991); Hilfiker et al. (2006); Klimakow et al. (2010); Lou et al. (2009); Nussinovitch et al. (1996); Schultheiss et al. (2010); Surov et al. (2012); Şimşek et al. (2000).
Felodipine (0.1 g, 0.26 mmol) and DABCO (0.03 g, 0.26 mmol) were dissolved in ethanol (10 ml, nominally 99.9%) at room temperature then the solvent was allowed to evaporate at ambient conditions. No precautions were taken to exclude water.
H atoms bound to C atoms were included in calculated positions and refined as riding, with C—H = 0.95 (aromatic), 0.98 (methyl) or 0.99 (methylene) Å, and with Uiso(H) = 1.2Ueq(C), or 1.5Ueq(C) for the methyl groups. The methyl groups were allowed to rotate around their local threefold axes. H atoms bound to N or O atoms were located in difference Fourier maps and refined with isotropic displacement parameters, with the following restraints: N1—H1 = 0.88 (1) Å, O1W—H1W and O1W—H2W = 0.84 (1) Å, and H1W···H2W = 1.37 (2) Å.
Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).
C18H19Cl2NO4·C6H12N2·H2O | F(000) = 1088 |
Mr = 514.43 | Dx = 1.330 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 9950 reflections |
a = 11.3003 (3) Å | θ = 2.4–25.5° |
b = 13.2721 (3) Å | µ = 0.29 mm−1 |
c = 17.2019 (4) Å | T = 150 K |
β = 95.398 (2)° | Block, colourless |
V = 2568.48 (11) Å3 | 0.48 × 0.32 × 0.18 mm |
Z = 4 |
Bruker–Nonius X8 APEXII CCD diffractometer | 4871 independent reflections |
Radiation source: fine-focus sealed tube | 3789 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.035 |
ω and ϕ scans | θmax = 25.7°, θmin = 3.6° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −13→13 |
Tmin = 0.818, Tmax = 0.949 | k = −14→16 |
42263 measured reflections | l = −17→20 |
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)] = 0.053 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.127 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0389P)2 + 2.9954P] where P = (Fo2 + 2Fc2)/3 |
4871 reflections | (Δ/σ)max < 0.001 |
323 parameters | Δρmax = 0.60 e Å−3 |
4 restraints | Δρmin = −0.40 e Å−3 |
C18H19Cl2NO4·C6H12N2·H2O | V = 2568.48 (11) Å3 |
Mr = 514.43 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 11.3003 (3) Å | µ = 0.29 mm−1 |
b = 13.2721 (3) Å | T = 150 K |
c = 17.2019 (4) Å | 0.48 × 0.32 × 0.18 mm |
β = 95.398 (2)° |
Bruker–Nonius X8 APEXII CCD diffractometer | 4871 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 3789 reflections with I > 2σ(I) |
Tmin = 0.818, Tmax = 0.949 | Rint = 0.035 |
42263 measured reflections |
R[F2 > 2σ(F2)] = 0.053 | 4 restraints |
wR(F2) = 0.127 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.10 | Δρmax = 0.60 e Å−3 |
4871 reflections | Δρmin = −0.40 e Å−3 |
323 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. Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane) - 0.4456 (0.0185) x - 11.0659 (0.0089) y + 9.4949 (0.0171) z = 2.7022 (0.0148) * -0.0119 (0.0012) C1 * 0.0115 (0.0012) C2 * -0.0115 (0.0012) C4 * 0.0119 (0.0012) C5 - 0.1352 (0.0036) N1 - 0.2933 (0.0038) C3 Rms deviation of fitted atoms = 0.0117 - 5.5260 (0.0109) x + 6.5918 (0.0121) y + 13.0716 (0.0122) z = 5.1713 (0.0110) Angle to previous plane (with approximate e.s.d.) = 90.00 (0.08) * -0.0109 (0.0017) C6 * 0.0039 (0.0019) C7 * 0.0055 (0.0020) C8 * -0.0079 (0.0020) C9 * 0.0008 (0.0018) C10 * 0.0086 (0.0017) C11 Rms deviation of fitted atoms = 0.0071 |
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 | ||
Cl1 | 0.83858 (7) | 0.50681 (6) | 0.49425 (5) | 0.0550 (2) | |
Cl2 | 0.78131 (6) | 0.30671 (6) | 0.57566 (4) | 0.0459 (2) | |
O1 | 0.34343 (18) | 0.27372 (16) | 0.67063 (11) | 0.0448 (5) | |
O2 | 0.53921 (17) | 0.25585 (16) | 0.66623 (10) | 0.0440 (5) | |
O3 | 0.64778 (19) | 0.02210 (16) | 0.37398 (12) | 0.0499 (5) | |
O4 | 0.73064 (17) | 0.11377 (16) | 0.47348 (12) | 0.0475 (5) | |
N1 | 0.3166 (2) | 0.13692 (17) | 0.44478 (13) | 0.0347 (5) | |
H1 | 0.2467 (14) | 0.124 (2) | 0.4209 (15) | 0.041 (8)* | |
C1 | 0.3176 (2) | 0.18632 (19) | 0.51539 (15) | 0.0320 (6) | |
C2 | 0.4217 (2) | 0.21324 (19) | 0.55411 (14) | 0.0288 (6) | |
C3 | 0.5367 (2) | 0.20315 (18) | 0.51566 (14) | 0.0277 (5) | |
H3A | 0.6010 | 0.1820 | 0.5563 | 0.033* | |
C4 | 0.5256 (2) | 0.12318 (19) | 0.45161 (14) | 0.0294 (6) | |
C5 | 0.4178 (2) | 0.09654 (19) | 0.41797 (15) | 0.0315 (6) | |
C6 | 0.5712 (2) | 0.30506 (18) | 0.48244 (13) | 0.0257 (5) | |
C7 | 0.4920 (2) | 0.3517 (2) | 0.42655 (15) | 0.0323 (6) | |
H7A | 0.4177 | 0.3205 | 0.4116 | 0.039* | |
C8 | 0.5186 (3) | 0.4423 (2) | 0.39224 (17) | 0.0417 (7) | |
H8A | 0.4628 | 0.4722 | 0.3544 | 0.050* | |
C9 | 0.6256 (3) | 0.4891 (2) | 0.41283 (17) | 0.0410 (7) | |
H9A | 0.6449 | 0.5507 | 0.3888 | 0.049* | |
C10 | 0.7039 (2) | 0.4457 (2) | 0.46847 (16) | 0.0353 (6) | |
C11 | 0.6777 (2) | 0.3546 (2) | 0.50397 (14) | 0.0298 (6) | |
C12 | 0.1964 (2) | 0.2023 (2) | 0.54251 (19) | 0.0458 (7) | |
H12A | 0.1837 | 0.2744 | 0.5509 | 0.069* | |
H12B | 0.1906 | 0.1658 | 0.5915 | 0.069* | |
H12C | 0.1357 | 0.1772 | 0.5028 | 0.069* | |
C13 | 0.4269 (2) | 0.2505 (2) | 0.63449 (15) | 0.0322 (6) | |
C14 | 0.5566 (3) | 0.2835 (3) | 0.74790 (17) | 0.0576 (9) | |
H14A | 0.4939 | 0.2529 | 0.7768 | 0.069* | |
H14B | 0.5528 | 0.3576 | 0.7537 | 0.069* | |
C15 | 0.6751 (3) | 0.2457 (3) | 0.77879 (19) | 0.0589 (9) | |
H15A | 0.6875 | 0.2591 | 0.8350 | 0.088* | |
H15B | 0.7367 | 0.2800 | 0.7522 | 0.088* | |
H15C | 0.6795 | 0.1730 | 0.7696 | 0.088* | |
C16 | 0.6367 (2) | 0.0800 (2) | 0.42826 (16) | 0.0340 (6) | |
C17 | 0.8482 (3) | 0.0845 (3) | 0.4543 (2) | 0.0617 (10) | |
H17A | 0.9072 | 0.1317 | 0.4786 | 0.093* | |
H17B | 0.8505 | 0.0858 | 0.3975 | 0.093* | |
H17C | 0.8661 | 0.0163 | 0.4738 | 0.093* | |
C18 | 0.3901 (3) | 0.0229 (2) | 0.35220 (16) | 0.0402 (7) | |
H18A | 0.4635 | −0.0105 | 0.3401 | 0.060* | |
H18B | 0.3551 | 0.0590 | 0.3059 | 0.060* | |
H18C | 0.3337 | −0.0276 | 0.3678 | 0.060* | |
N3 | 0.0089 (2) | 0.45767 (17) | 0.23719 (13) | 0.0391 (6) | |
N2 | 0.0634 (2) | 0.29281 (17) | 0.30913 (13) | 0.0385 (6) | |
C19 | 0.1385 (3) | 0.4515 (2) | 0.25766 (18) | 0.0449 (7) | |
H19A | 0.1657 | 0.5115 | 0.2886 | 0.054* | |
H19B | 0.1797 | 0.4510 | 0.2094 | 0.054* | |
C20 | 0.1704 (2) | 0.3553 (2) | 0.30526 (18) | 0.0426 (7) | |
H20A | 0.2315 | 0.3167 | 0.2804 | 0.051* | |
H20B | 0.2034 | 0.3738 | 0.3587 | 0.051* | |
C21 | −0.0286 (3) | 0.3709 (2) | 0.18810 (16) | 0.0413 (7) | |
H21A | 0.0055 | 0.3764 | 0.1373 | 0.050* | |
H21B | −0.1163 | 0.3707 | 0.1779 | 0.050* | |
C22 | 0.0127 (3) | 0.2722 (2) | 0.22839 (17) | 0.0435 (7) | |
H22A | −0.0555 | 0.2255 | 0.2292 | 0.052* | |
H22B | 0.0734 | 0.2397 | 0.1989 | 0.052* | |
C23 | −0.0504 (3) | 0.4524 (2) | 0.30974 (17) | 0.0427 (7) | |
H23A | −0.1372 | 0.4606 | 0.2976 | 0.051* | |
H23B | −0.0214 | 0.5076 | 0.3453 | 0.051* | |
C24 | −0.0240 (2) | 0.3497 (2) | 0.35001 (16) | 0.0376 (6) | |
H24A | 0.0076 | 0.3607 | 0.4050 | 0.045* | |
H24B | −0.0984 | 0.3104 | 0.3498 | 0.045* | |
O1W | 0.09117 (19) | 0.10036 (17) | 0.36927 (13) | 0.0440 (5) | |
H1W | 0.090 (4) | 0.1592 (14) | 0.350 (2) | 0.13 (2)* | |
H2W | 0.062 (4) | 0.062 (2) | 0.3331 (18) | 0.105 (17)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0544 (5) | 0.0563 (5) | 0.0556 (5) | −0.0274 (4) | 0.0124 (4) | −0.0182 (4) |
Cl2 | 0.0391 (4) | 0.0602 (5) | 0.0366 (4) | −0.0025 (3) | −0.0065 (3) | 0.0002 (3) |
O1 | 0.0464 (12) | 0.0533 (13) | 0.0369 (11) | 0.0066 (10) | 0.0162 (9) | −0.0019 (9) |
O2 | 0.0438 (12) | 0.0630 (13) | 0.0252 (10) | 0.0135 (10) | 0.0030 (8) | −0.0079 (9) |
O3 | 0.0544 (13) | 0.0449 (12) | 0.0530 (13) | 0.0053 (10) | 0.0179 (10) | −0.0125 (11) |
O4 | 0.0348 (11) | 0.0553 (13) | 0.0533 (13) | 0.0096 (10) | 0.0088 (9) | −0.0109 (11) |
N1 | 0.0303 (13) | 0.0341 (13) | 0.0393 (13) | −0.0047 (10) | 0.0018 (10) | −0.0026 (10) |
C1 | 0.0343 (14) | 0.0277 (14) | 0.0355 (14) | −0.0019 (11) | 0.0119 (11) | 0.0046 (11) |
C2 | 0.0335 (14) | 0.0262 (13) | 0.0275 (13) | 0.0000 (11) | 0.0080 (11) | 0.0048 (11) |
C3 | 0.0332 (14) | 0.0255 (13) | 0.0250 (12) | 0.0037 (11) | 0.0064 (10) | 0.0030 (10) |
C4 | 0.0375 (15) | 0.0246 (13) | 0.0269 (13) | −0.0006 (11) | 0.0076 (11) | 0.0043 (10) |
C5 | 0.0424 (16) | 0.0250 (13) | 0.0288 (13) | −0.0015 (12) | 0.0116 (12) | 0.0050 (11) |
C6 | 0.0297 (13) | 0.0247 (13) | 0.0237 (12) | 0.0025 (11) | 0.0076 (10) | −0.0016 (10) |
C7 | 0.0316 (14) | 0.0291 (14) | 0.0362 (14) | −0.0009 (11) | 0.0038 (11) | 0.0044 (12) |
C8 | 0.0445 (17) | 0.0344 (16) | 0.0460 (17) | 0.0071 (13) | 0.0035 (13) | 0.0123 (13) |
C9 | 0.0506 (18) | 0.0259 (14) | 0.0484 (17) | −0.0022 (13) | 0.0145 (14) | 0.0030 (13) |
C10 | 0.0400 (16) | 0.0298 (14) | 0.0375 (15) | −0.0102 (12) | 0.0118 (12) | −0.0122 (12) |
C11 | 0.0304 (13) | 0.0346 (15) | 0.0248 (13) | 0.0033 (11) | 0.0050 (10) | −0.0071 (11) |
C12 | 0.0347 (16) | 0.0508 (19) | 0.0538 (19) | −0.0051 (14) | 0.0135 (14) | −0.0019 (15) |
C13 | 0.0405 (16) | 0.0269 (14) | 0.0307 (14) | 0.0033 (12) | 0.0108 (12) | 0.0061 (11) |
C14 | 0.061 (2) | 0.083 (3) | 0.0284 (15) | 0.0241 (19) | −0.0003 (14) | −0.0120 (16) |
C15 | 0.056 (2) | 0.082 (3) | 0.0382 (17) | 0.0170 (19) | 0.0045 (15) | −0.0073 (17) |
C16 | 0.0423 (16) | 0.0255 (14) | 0.0364 (15) | 0.0039 (12) | 0.0158 (12) | 0.0047 (12) |
C17 | 0.0389 (18) | 0.066 (2) | 0.083 (3) | 0.0104 (16) | 0.0204 (17) | −0.018 (2) |
C18 | 0.0475 (17) | 0.0357 (16) | 0.0381 (16) | −0.0093 (13) | 0.0081 (13) | −0.0054 (12) |
N3 | 0.0473 (14) | 0.0345 (13) | 0.0356 (13) | 0.0019 (11) | 0.0053 (10) | 0.0003 (10) |
N2 | 0.0455 (14) | 0.0321 (13) | 0.0368 (13) | 0.0044 (11) | −0.0017 (10) | −0.0034 (10) |
C19 | 0.0450 (17) | 0.0450 (18) | 0.0450 (17) | −0.0105 (14) | 0.0053 (13) | −0.0041 (14) |
C20 | 0.0344 (15) | 0.0485 (18) | 0.0450 (17) | 0.0027 (13) | 0.0038 (12) | −0.0086 (14) |
C21 | 0.0428 (17) | 0.0456 (17) | 0.0350 (15) | 0.0042 (14) | 0.0008 (12) | −0.0068 (13) |
C22 | 0.0531 (18) | 0.0354 (16) | 0.0413 (16) | −0.0012 (14) | −0.0002 (14) | −0.0097 (13) |
C23 | 0.0524 (18) | 0.0375 (16) | 0.0391 (16) | 0.0071 (14) | 0.0095 (13) | −0.0036 (13) |
C24 | 0.0399 (16) | 0.0397 (16) | 0.0327 (14) | −0.0017 (13) | 0.0014 (12) | −0.0002 (12) |
O1W | 0.0417 (12) | 0.0376 (12) | 0.0512 (13) | −0.0037 (10) | −0.0036 (10) | 0.0012 (11) |
Cl1—C10 | 1.745 (3) | C14—H14A | 0.9900 |
Cl2—C11 | 1.739 (3) | C14—H14B | 0.9900 |
O1—C13 | 1.217 (3) | C15—H15A | 0.9800 |
O2—C13 | 1.336 (3) | C15—H15B | 0.9800 |
O2—C14 | 1.447 (3) | C15—H15C | 0.9800 |
O3—C16 | 1.225 (3) | C17—H17A | 0.9800 |
O4—C16 | 1.333 (3) | C17—H17B | 0.9800 |
O4—C17 | 1.451 (3) | C17—H17C | 0.9800 |
N1—C1 | 1.379 (3) | C18—H18A | 0.9800 |
N1—C5 | 1.381 (3) | C18—H18B | 0.9800 |
N1—H1 | 0.872 (10) | C18—H18C | 0.9800 |
C1—C2 | 1.344 (4) | N3—C21 | 1.467 (4) |
C1—C12 | 1.503 (4) | N3—C23 | 1.472 (4) |
C2—C13 | 1.464 (4) | N3—C19 | 1.477 (4) |
C2—C3 | 1.519 (3) | N2—C24 | 1.473 (4) |
C3—C4 | 1.526 (3) | N2—C20 | 1.473 (4) |
C3—C6 | 1.533 (3) | N2—C22 | 1.477 (4) |
C3—H3A | 1.0000 | C19—C20 | 1.541 (4) |
C4—C5 | 1.346 (4) | C19—H19A | 0.9900 |
C4—C16 | 1.470 (4) | C19—H19B | 0.9900 |
C5—C18 | 1.505 (4) | C20—H20A | 0.9900 |
C6—C11 | 1.390 (4) | C20—H20B | 0.9900 |
C6—C7 | 1.395 (4) | C21—C22 | 1.534 (4) |
C7—C8 | 1.385 (4) | C21—H21A | 0.9900 |
C7—H7A | 0.9500 | C21—H21B | 0.9900 |
C8—C9 | 1.376 (4) | C22—H22A | 0.9900 |
C8—H8A | 0.9500 | C22—H22B | 0.9900 |
C9—C10 | 1.368 (4) | C23—C24 | 1.545 (4) |
C9—H9A | 0.9500 | C23—H23A | 0.9900 |
C10—C11 | 1.399 (4) | C23—H23B | 0.9900 |
C12—H12A | 0.9800 | C24—H24A | 0.9900 |
C12—H12B | 0.9800 | C24—H24B | 0.9900 |
C12—H12C | 0.9800 | O1W—H1W | 0.846 (10) |
C14—C15 | 1.481 (4) | O1W—H2W | 0.847 (10) |
C13—O2—C14 | 116.6 (2) | H15A—C15—H15C | 109.5 |
C16—O4—C17 | 118.2 (2) | H15B—C15—H15C | 109.5 |
C1—N1—C5 | 122.7 (2) | O3—C16—O4 | 121.6 (2) |
C1—N1—H1 | 116.0 (19) | O3—C16—C4 | 127.1 (3) |
C5—N1—H1 | 121 (2) | O4—C16—C4 | 111.3 (2) |
C2—C1—N1 | 119.8 (2) | O4—C17—H17A | 109.5 |
C2—C1—C12 | 126.1 (2) | O4—C17—H17B | 109.5 |
N1—C1—C12 | 114.1 (2) | H17A—C17—H17B | 109.5 |
C1—C2—C13 | 120.9 (2) | O4—C17—H17C | 109.5 |
C1—C2—C3 | 120.4 (2) | H17A—C17—H17C | 109.5 |
C13—C2—C3 | 118.8 (2) | H17B—C17—H17C | 109.5 |
C2—C3—C4 | 111.1 (2) | C5—C18—H18A | 109.5 |
C2—C3—C6 | 110.0 (2) | C5—C18—H18B | 109.5 |
C4—C3—C6 | 110.55 (19) | H18A—C18—H18B | 109.5 |
C2—C3—H3A | 108.4 | C5—C18—H18C | 109.5 |
C4—C3—H3A | 108.4 | H18A—C18—H18C | 109.5 |
C6—C3—H3A | 108.4 | H18B—C18—H18C | 109.5 |
C5—C4—C16 | 122.8 (2) | C21—N3—C23 | 108.7 (2) |
C5—C4—C3 | 120.2 (2) | C21—N3—C19 | 108.7 (2) |
C16—C4—C3 | 117.0 (2) | C23—N3—C19 | 108.4 (2) |
C4—C5—N1 | 119.9 (2) | C24—N2—C20 | 108.8 (2) |
C4—C5—C18 | 127.5 (2) | C24—N2—C22 | 109.0 (2) |
N1—C5—C18 | 112.5 (2) | C20—N2—C22 | 108.0 (2) |
C11—C6—C7 | 117.2 (2) | N3—C19—C20 | 110.4 (2) |
C11—C6—C3 | 124.2 (2) | N3—C19—H19A | 109.6 |
C7—C6—C3 | 118.6 (2) | C20—C19—H19A | 109.6 |
C8—C7—C6 | 121.9 (3) | N3—C19—H19B | 109.6 |
C8—C7—H7A | 119.1 | C20—C19—H19B | 109.6 |
C6—C7—H7A | 119.1 | H19A—C19—H19B | 108.1 |
C9—C8—C7 | 120.2 (3) | N2—C20—C19 | 109.8 (2) |
C9—C8—H8A | 119.9 | N2—C20—H20A | 109.7 |
C7—C8—H8A | 119.9 | C19—C20—H20A | 109.7 |
C10—C9—C8 | 119.0 (3) | N2—C20—H20B | 109.7 |
C10—C9—H9A | 120.5 | C19—C20—H20B | 109.7 |
C8—C9—H9A | 120.5 | H20A—C20—H20B | 108.2 |
C9—C10—C11 | 121.4 (2) | N3—C21—C22 | 110.6 (2) |
C9—C10—Cl1 | 118.2 (2) | N3—C21—H21A | 109.5 |
C11—C10—Cl1 | 120.4 (2) | C22—C21—H21A | 109.5 |
C6—C11—C10 | 120.4 (2) | N3—C21—H21B | 109.5 |
C6—C11—Cl2 | 121.6 (2) | C22—C21—H21B | 109.5 |
C10—C11—Cl2 | 118.0 (2) | H21A—C21—H21B | 108.1 |
C1—C12—H12A | 109.5 | N2—C22—C21 | 110.0 (2) |
C1—C12—H12B | 109.5 | N2—C22—H22A | 109.7 |
H12A—C12—H12B | 109.5 | C21—C22—H22A | 109.7 |
C1—C12—H12C | 109.5 | N2—C22—H22B | 109.7 |
H12A—C12—H12C | 109.5 | C21—C22—H22B | 109.7 |
H12B—C12—H12C | 109.5 | H22A—C22—H22B | 108.2 |
O1—C13—O2 | 122.0 (2) | N3—C23—C24 | 109.7 (2) |
O1—C13—C2 | 127.2 (3) | N3—C23—H23A | 109.7 |
O2—C13—C2 | 110.9 (2) | C24—C23—H23A | 109.7 |
O2—C14—C15 | 107.3 (2) | N3—C23—H23B | 109.7 |
O2—C14—H14A | 110.2 | C24—C23—H23B | 109.7 |
C15—C14—H14A | 110.2 | H23A—C23—H23B | 108.2 |
O2—C14—H14B | 110.2 | N2—C24—C23 | 110.4 (2) |
C15—C14—H14B | 110.2 | N2—C24—H24A | 109.6 |
H14A—C14—H14B | 108.5 | C23—C24—H24A | 109.6 |
C14—C15—H15A | 109.5 | N2—C24—H24B | 109.6 |
C14—C15—H15B | 109.5 | C23—C24—H24B | 109.6 |
H15A—C15—H15B | 109.5 | H24A—C24—H24B | 108.1 |
C14—C15—H15C | 109.5 | H1W—O1W—H2W | 106 (2) |
C5—N1—C1—C2 | 12.4 (4) | C3—C6—C11—Cl2 | −3.0 (3) |
C5—N1—C1—C12 | −166.0 (2) | C9—C10—C11—C6 | 0.9 (4) |
N1—C1—C2—C13 | −169.8 (2) | Cl1—C10—C11—C6 | −178.90 (19) |
C12—C1—C2—C13 | 8.4 (4) | C9—C10—C11—Cl2 | −178.6 (2) |
N1—C1—C2—C3 | 8.7 (4) | Cl1—C10—C11—Cl2 | 1.6 (3) |
C12—C1—C2—C3 | −173.0 (2) | C14—O2—C13—O1 | 4.5 (4) |
C1—C2—C3—C4 | −24.4 (3) | C14—O2—C13—C2 | −174.9 (3) |
C13—C2—C3—C4 | 154.2 (2) | C1—C2—C13—O1 | −10.4 (4) |
C1—C2—C3—C6 | 98.4 (3) | C3—C2—C13—O1 | 171.0 (3) |
C13—C2—C3—C6 | −83.0 (3) | C1—C2—C13—O2 | 169.1 (2) |
C2—C3—C4—C5 | 22.0 (3) | C3—C2—C13—O2 | −9.5 (3) |
C6—C3—C4—C5 | −100.5 (3) | C13—O2—C14—C15 | 157.3 (3) |
C2—C3—C4—C16 | −159.3 (2) | C17—O4—C16—O3 | 3.3 (4) |
C6—C3—C4—C16 | 78.2 (3) | C17—O4—C16—C4 | −175.2 (3) |
C16—C4—C5—N1 | 177.4 (2) | C5—C4—C16—O3 | 5.5 (4) |
C3—C4—C5—N1 | −4.1 (4) | C3—C4—C16—O3 | −173.1 (2) |
C16—C4—C5—C18 | −1.3 (4) | C5—C4—C16—O4 | −176.1 (2) |
C3—C4—C5—C18 | 177.3 (2) | C3—C4—C16—O4 | 5.3 (3) |
C1—N1—C5—C4 | −14.8 (4) | C21—N3—C19—C20 | −62.0 (3) |
C1—N1—C5—C18 | 164.0 (2) | C23—N3—C19—C20 | 56.0 (3) |
C2—C3—C6—C11 | 121.3 (3) | C24—N2—C20—C19 | −62.3 (3) |
C4—C3—C6—C11 | −115.6 (3) | C22—N2—C20—C19 | 55.9 (3) |
C2—C3—C6—C7 | −59.1 (3) | N3—C19—C20—N2 | 5.9 (3) |
C4—C3—C6—C7 | 64.0 (3) | C23—N3—C21—C22 | −63.7 (3) |
C11—C6—C7—C8 | 1.5 (4) | C19—N3—C21—C22 | 54.1 (3) |
C3—C6—C7—C8 | −178.0 (2) | C24—N2—C22—C21 | 54.0 (3) |
C6—C7—C8—C9 | 0.0 (4) | C20—N2—C22—C21 | −64.1 (3) |
C7—C8—C9—C10 | −1.1 (4) | N3—C21—C22—N2 | 7.8 (3) |
C8—C9—C10—C11 | 0.7 (4) | C21—N3—C23—C24 | 55.1 (3) |
C8—C9—C10—Cl1 | −179.5 (2) | C19—N3—C23—C24 | −62.8 (3) |
C7—C6—C11—C10 | −1.9 (3) | C20—N2—C24—C23 | 55.3 (3) |
C3—C6—C11—C10 | 177.6 (2) | C22—N2—C24—C23 | −62.2 (3) |
C7—C6—C11—Cl2 | 177.50 (19) | N3—C23—C24—N2 | 6.6 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1W | 0.87 (1) | 1.92 (1) | 2.791 (3) | 178 (3) |
O1W—H1W···N2 | 0.85 (1) | 1.92 (1) | 2.763 (3) | 172 (5) |
O1W—H2W···N3i | 0.85 (1) | 1.96 (1) | 2.798 (3) | 171 (4) |
Symmetry code: (i) −x, y−1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C18H19Cl2NO4·C6H12N2·H2O |
Mr | 514.43 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 150 |
a, b, c (Å) | 11.3003 (3), 13.2721 (3), 17.2019 (4) |
β (°) | 95.398 (2) |
V (Å3) | 2568.48 (11) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.29 |
Crystal size (mm) | 0.48 × 0.32 × 0.18 |
Data collection | |
Diffractometer | Bruker–Nonius X8 APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.818, 0.949 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 42263, 4871, 3789 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.611 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.053, 0.127, 1.10 |
No. of reflections | 4871 |
No. of parameters | 323 |
No. of restraints | 4 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.60, −0.40 |
Computer programs: APEX2 (Bruker, 2010), SAINT (Bruker, 2010), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1W | 0.872 (10) | 1.919 (11) | 2.791 (3) | 178 (3) |
O1W—H1W···N2 | 0.846 (10) | 1.923 (13) | 2.763 (3) | 172 (5) |
O1W—H2W···N3i | 0.847 (10) | 1.959 (12) | 2.798 (3) | 171 (4) |
Symmetry code: (i) −x, y−1/2, −z+1/2. |
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Felodipine [systematic name: ethyl methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] is a calcium-channel blocking agent that is widely used for treatment of hypertension and angina (Nussinovitch et al., 1996). The compound belongs to Class II of the Biopharmaceutical Classification Scheme (Amidon et al., 1995) because it is effectively absorbed from the gastro intestine but is practically insoluble in water. One strategy that might be applied to enhance the aqueous solubility of felodipine is to generate alternative solid forms (Hilfiker et al., 2006). To this end, we have recently reported the structures and properties of four felodipine polymorphs (Surov et al., 2012). We have also carried out some cocrystallization trials, and we report here the structure of a hydrated cocrystal of felodipine with diazabicyclo[2.2.2]octane (DABCO), (I).
The asymmetric unit of (I) comprises one molecule of felodipine, one molecule of DABCO and one water molecule (Fig. 1). The conformation of the felodipine molecule is typical for this class of molecule (Goldmann & Stoltefuss, 1991), comprising two approximately planar sections with the dichlorophenyl unit lying perpendicular to the plane of the remainder of the molecule. The 1,4-dihydropyridine (1,4-DHP) ring (N1/C1–C5) adopts a shallow boat conformation, in which atoms N1 and C3 lie 0.135 (4) and 0.293 (4) Å, respectively, from the mean plane defined by C1/C2/C4/C5. These values are consistent with a previous database study for 1,4-DHP rings (Şimşek et al., 2000), which showed that atom C3 typically lies 0.30 Å from the defined plane, while the deviation of atom N1 lies in the range 0.04–0.19 Å. The dihedral angle between the dichlorophenyl ring and the mean plane defined by C1/C2/C4/C5 is 90.00 (8)°. The O atoms of the methyl and ethyl ester groups are approximately in the plane of the 1,4-DHP ring on account of π-electron conjugation between the oxo groups and the double bonds in the ring.
The DABCO and water molecules are linked through O—H···N hydrogen bonds (Table 1) into chains around the 21 screw axes in space group P21/c (Fig. 2). The felodipine molecules form N—H···O hydrogen bonds to water, adopting pendant positions on alternating sides of the hydrogen-bonded chains. The felodipine molecules in adjacent chains meet in two distinct intermolecular arrangements, both of which are formed across crystallographic inversion centres (Fig. 3). In one interaction, the 1,4-DHP rings of the felodipine molecules adopt a back-to-back arrangement, with a centroid–centroid distance of 4.605 (3) Å [symmetry code: (ii) -x+1, -y, -z+1]. The molecules are offset so that methyl group C18 lies above C3 [C18···C3ii = 3.808 (4) Å] and atom C16 of the methyl ester group lies above atom N1 [N1···C16ii = 3.622 (3) Å]. In the other intermolecular interaction, the dichlorophenyl rings adopt an offset π-stacked arrangement, with a centroid–centroid distance of 4.028 (2) Å [symmetry code: (iii) -x+1, -y+1, -z+1]. The back-to-back arrangement is present in all four felodipine polymorphs (Surov et al., 2012), although the lateral offset of the molecules is variable in each structure. The π-stacked arrangement of dichlorophenyl rings is present only in felodipine polymorph I (Fossheim, 1986).
The Cambridge Structural Database (CSD; Version 5.33 plus updates; Allen, 2002) includes one other cocrystal of felodipine, containing formamide in a 1:1 ratio (Lou et al., 2009). In that structure (Fig. 4), the felodipine molecules form N—H···O hydrogen bonds to formamide and dimeric formamide motifs can be considered to yield a pseudo-2:1 cocrystal in which the formamide dimer constitutes a supramolecular unit that bridges between two felodipine molecules. The CSD also contains three cocrystals of the closely related molecule nifedipine, (II), which has two methyl esters and one nitro group at the 2-position of the phenyl ring. In a 2:1 cocrystal of nifedipine with 1,4-dioxane (Caira et al., 2003), two nifedipine molecules are linked by a 1,4-dioxane molecule into a trimeric hydrogen-bonded unit similar to that described for felodipine–formamide. In the cocrystal of nifedipine with dimethyl sufoxide (DMSO; Klimakow et al., 2010), nifedipine forms an N—H···O hydrogen bond to the O atom of DMSO. The resulting cocrystal is essentially isostructural with nifedipine–1,4-dioxane (2/1), with a pair of dimethyl sufoxide molecules occupying the position of each 1,4-dioxane molecule. The cocrystal of nifedipine with pyrazine (Schultheiss et al., 2010) is unexpected, because nifedipine forms N—H···O hydrogen bonds to the O atoms of the methyl esters, while the pyrazine molecule is not involved in any hydrogen-bonding interaction. In that case, one factor that must contribute to the observed structure is the relative strengths of the N—H···O and N—H···N hydrogen bonds. For felodipine–DABCO, direct N—H···N hydrogen bonding between the two molecules is probably also discouraged by steric constraints resulting from the presence of the two methyl groups on either side of the N—H group in felodipine.