Fexofenadine [systematic name: (±)-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidinium-1-yl]-butyl}phenyl)-2-methylpropionate], crystallizes in two forms,
viz. as the methanol disolvate, C
32H
39NO
4·2CH
4O, and as the dihydrate, C
32H
39NO
4·2H
2O. It exists in the two structures as a zwitterion, which self-assembles as dimers sustained by a pair of charged-assisted N—H
OOC hydrogen bonds. In the methanol disolvate, the supramolecular organization consists of discrete fexofenadine dimers solvated by four molecules of methanol. The dihydrate structure is sustained by a more extended hydrogen-bonding scheme, wherein the hydrated dimeric entities are interlinked by additional hydrogen bonds. The fexofenadine molecule adopts different and differently disordered conformations of the 1-hydroxybutyl residue in the two structures.
Supporting information
CCDC references: 294346; 294347
Crude fexofenadine powder was obtained from Teva Pharmaceutical Industries Ltd. Compound (I) was crystallized by slow evaporation from methanol. Compound (II) was crystallized by slow evaporation from wet acetonitrile. Thermal analyses of both compounds confirmed their chemical purity. In both cases, the crystals obtained were characterized by relatively high mosaicity, which is most probably affected by the conformational disorder of the fexofenadine compound, and yielded generally weak diffraction. Correspondingly, the crystallographic refinements were based on data sets containing a high percentage of weak reflections and they concluded in relatively high R values. Attempts to crystallize unsolvated fexofenadine were not successful.
Both compounds reveal structural disorder, which results in two posssible positions for the central O2—H group in each structure. In the refined structural models, the relative occupancies of these positions refined to 0.867 (5) (O2A) and 0.133 (5) (O2B) in (I), and 0.573 (5) (O2A) and O.427 (5) (O2B) in (II), while the bond lengths for C22—O2A and C22—O2B were restrained to be similar. In both structures, the methyl H atoms were constrained to an ideal geometry, with C—H = 0.98 Å and Uiso(H) = 1.5Ueq(C), but were allowed to rotate freely about the parent C—C bonds. All other H atoms bound to C atoms were placed in idealized positions and were constrained to ride on their parent atoms, with C—H distances in the range 0.95–0.99 Å and with Uiso(H) = 1.2Ueq(C). In (I), H atoms attached to N and O atoms (except for the minor O2B site) were located in difference Fourier maps and their parameters were refined freely (except for the H atom attached to O2A, which did not refine well and was fixed in its initial position). The H atom attached to atom O2B was fixed in an initially calculated position, with Uiso(H) = 1.2Ueq(O2B). In (II), only H atoms bound to atoms O1 and N1 were located in a difference Fourier map and their parameters were refined freely. The H atoms attached to the disordered O2A and O2B sites, as well as water H atoms, were placed in calculated positions by taking into account the most probable hydrogen-bonding interactions, as indicated by O···O intermolecular distances <3.0 Å. These H atoms did not refine well and were subsequently held fixed in their initial positions. The Uiso(H) parameters were refined for the water H atoms, while the H atoms on O2A and O2B were assigned Uiso(H) = 1.2Ueq(O).
For both compounds, data collection: COLLECT (Nonius, 1999); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and Mercury (Bruno et al., 2002); software used to prepare material for publication: SHELXL97.
(I) (±)-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidinium-1-yl]- butyl}phenyl)-2-methylpropionate methanol disolvate
top
Crystal data top
C32H39NO4·2CH4O | F(000) = 1224 |
Mr = 565.73 | Dx = 1.225 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 6836 reflections |
a = 20.8661 (3) Å | θ = 2.1–27.9° |
b = 9.6138 (2) Å | µ = 0.08 mm−1 |
c = 16.0702 (5) Å | T = 110 K |
β = 107.8870 (8)° | Prism, colourless |
V = 3067.90 (12) Å3 | 0.30 × 0.25 × 0.25 mm |
Z = 4 | |
Data collection top
Nonius KappaCCD area-detector diffractometer | 4405 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.072 |
Graphite monochromator | θmax = 27.9°, θmin = 2.1° |
Detector resolution: 56 microns pixels mm-1 | h = −27→25 |
0.8° ϕ and ω scans | k = −11→11 |
22588 measured reflections | l = −21→21 |
7172 independent reflections | |
Refinement top
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)] = 0.064 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.168 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0734P)2 + 1.5166P] where P = (Fo2 + 2Fc2)/3 |
7172 reflections | (Δ/σ)max = 0.007 |
396 parameters | Δρmax = 0.42 e Å−3 |
3 restraints | Δρmin = −0.41 e Å−3 |
Crystal data top
C32H39NO4·2CH4O | V = 3067.90 (12) Å3 |
Mr = 565.73 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 20.8661 (3) Å | µ = 0.08 mm−1 |
b = 9.6138 (2) Å | T = 110 K |
c = 16.0702 (5) Å | 0.30 × 0.25 × 0.25 mm |
β = 107.8870 (8)° | |
Data collection top
Nonius KappaCCD area-detector diffractometer | 4405 reflections with I > 2σ(I) |
22588 measured reflections | Rint = 0.072 |
7172 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.064 | 3 restraints |
wR(F2) = 0.168 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.42 e Å−3 |
7172 reflections | Δρmin = −0.41 e Å−3 |
396 parameters | |
Special details top
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. The O2 site reveals a slight disorder, with relative occupancies of 86.7 (5)% (O2A) and 13.3 (5)% (O2B). |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
O1 | 0.85065 (8) | 0.25534 (16) | 0.95396 (10) | 0.0268 (4) | |
H1O | 0.8327 (15) | 0.202 (3) | 0.989 (2) | 0.049 (9)* | |
O2A | 0.46297 (10) | 0.06053 (17) | 0.82889 (13) | 0.0308 (6) | 0.867 (5) |
H2OA | 0.5006 | 0.0873 | 0.8727 | 0.093 (16)* | 0.867 (5) |
O2B | 0.4092 (6) | 0.0485 (9) | 0.7607 (8) | 0.027 (4)* | 0.133 (5) |
H2OB | 0.4287 | 0.0084 | 0.7189 | 0.032* | 0.133 (5) |
O3 | 0.36132 (8) | 0.58642 (15) | 1.11448 (10) | 0.0287 (4) | |
O4 | 0.32270 (8) | 0.70335 (15) | 0.98886 (11) | 0.0297 (4) | |
N1 | 0.63474 (9) | 0.24557 (18) | 0.74387 (13) | 0.0215 (4) | |
H1N | 0.6284 (13) | 0.292 (3) | 0.7906 (17) | 0.032 (7)* | |
C1 | 0.93531 (12) | 0.3742 (2) | 0.88167 (17) | 0.0315 (6) | |
H1 | 0.9292 | 0.4061 | 0.9347 | 0.038* | |
C2 | 0.97854 (14) | 0.4452 (3) | 0.84589 (19) | 0.0399 (6) | |
H2 | 1.0021 | 0.5246 | 0.8750 | 0.048* | |
C3 | 0.98773 (14) | 0.4015 (3) | 0.76802 (19) | 0.0407 (7) | |
H3 | 1.0172 | 0.4507 | 0.7436 | 0.049* | |
C4 | 0.95328 (13) | 0.2852 (3) | 0.72634 (18) | 0.0370 (6) | |
H4 | 0.9589 | 0.2545 | 0.6728 | 0.044* | |
C5 | 0.91075 (12) | 0.2135 (2) | 0.76240 (16) | 0.0312 (5) | |
H5 | 0.8878 | 0.1334 | 0.7334 | 0.037* | |
C6 | 0.90082 (11) | 0.2564 (2) | 0.84048 (15) | 0.0255 (5) | |
C7 | 0.85197 (11) | 0.1790 (2) | 0.87858 (15) | 0.0247 (5) | |
C8 | 0.87673 (12) | 0.0295 (2) | 0.90400 (15) | 0.0258 (5) | |
C9 | 0.91272 (12) | −0.0023 (2) | 0.99032 (16) | 0.0303 (5) | |
H9 | 0.9234 | 0.0697 | 1.0329 | 0.036* | |
C10 | 0.93327 (13) | −0.1383 (3) | 1.01516 (17) | 0.0346 (6) | |
H10 | 0.9574 | −0.1583 | 1.0744 | 0.042* | |
C11 | 0.91873 (13) | −0.2435 (3) | 0.95417 (18) | 0.0369 (6) | |
H11 | 0.9322 | −0.3362 | 0.9714 | 0.044* | |
C12 | 0.88444 (14) | −0.2137 (3) | 0.86785 (19) | 0.0396 (6) | |
H12 | 0.8753 | −0.2859 | 0.8254 | 0.048* | |
C13 | 0.86332 (13) | −0.0792 (2) | 0.84290 (17) | 0.0336 (6) | |
H13 | 0.8394 | −0.0603 | 0.7834 | 0.040* | |
C14 | 0.78052 (11) | 0.1794 (2) | 0.81106 (15) | 0.0229 (5) | |
H14 | 0.7832 | 0.1305 | 0.7573 | 0.027* | |
C15 | 0.72809 (11) | 0.1041 (2) | 0.84322 (15) | 0.0252 (5) | |
H15A | 0.7432 | 0.0075 | 0.8595 | 0.030* | |
H15B | 0.7241 | 0.1514 | 0.8961 | 0.030* | |
C16 | 0.65971 (12) | 0.1017 (2) | 0.77358 (15) | 0.0252 (5) | |
H16A | 0.6630 | 0.0473 | 0.7227 | 0.030* | |
H16B | 0.6268 | 0.0546 | 0.7972 | 0.030* | |
C17 | 0.68667 (11) | 0.3260 (2) | 0.71555 (15) | 0.0244 (5) | |
H17A | 0.6709 | 0.4230 | 0.7021 | 0.029* | |
H17B | 0.6912 | 0.2840 | 0.6614 | 0.029* | |
C18 | 0.75475 (11) | 0.3272 (2) | 0.78479 (15) | 0.0246 (5) | |
H18A | 0.7513 | 0.3775 | 0.8370 | 0.029* | |
H18B | 0.7874 | 0.3774 | 0.7622 | 0.029* | |
C19 | 0.57039 (11) | 0.2413 (2) | 0.66770 (15) | 0.0242 (5) | |
H19A | 0.5790 | 0.1892 | 0.6191 | 0.029* | |
H19B | 0.5580 | 0.3376 | 0.6472 | 0.029* | |
C20 | 0.51128 (11) | 0.1749 (2) | 0.68867 (15) | 0.0256 (5) | |
H20A | 0.5260 | 0.0840 | 0.7171 | 0.031* | |
H20B | 0.4753 | 0.1566 | 0.6331 | 0.031* | |
C21 | 0.48148 (12) | 0.2607 (2) | 0.74773 (16) | 0.0257 (5) | |
H21A | 0.5184 | 0.2952 | 0.7983 | 0.031* | |
H21B | 0.4578 | 0.3424 | 0.7148 | 0.031* | |
C22 | 0.43287 (13) | 0.1779 (2) | 0.78063 (17) | 0.0305 (6) | |
H22A | 0.3979 | 0.1416 | 0.7275 | 0.037* | 0.867 (5) |
H22B | 0.4685 | 0.1476 | 0.8349 | 0.037* | 0.133 (5) |
C23 | 0.39524 (12) | 0.2615 (2) | 0.83062 (15) | 0.0266 (5) | |
C24 | 0.32577 (12) | 0.2531 (2) | 0.80871 (15) | 0.0263 (5) | |
H24 | 0.3015 | 0.2000 | 0.7592 | 0.032* | |
C25 | 0.29084 (12) | 0.3214 (2) | 0.85814 (15) | 0.0252 (5) | |
H25 | 0.2432 | 0.3133 | 0.8420 | 0.030* | |
C26 | 0.32455 (12) | 0.4012 (2) | 0.93066 (14) | 0.0226 (5) | |
C27 | 0.39454 (12) | 0.4119 (2) | 0.95153 (15) | 0.0251 (5) | |
H27 | 0.4187 | 0.4673 | 0.9999 | 0.030* | |
C28 | 0.42936 (12) | 0.3430 (2) | 0.90279 (15) | 0.0271 (5) | |
H28 | 0.4770 | 0.3514 | 0.9186 | 0.033* | |
C29 | 0.28703 (12) | 0.4647 (2) | 0.98987 (14) | 0.0247 (5) | |
C30 | 0.21488 (12) | 0.5093 (2) | 0.93878 (16) | 0.0301 (5) | |
H30A | 0.2162 | 0.5749 | 0.8926 | 0.045* | |
H30B | 0.1939 | 0.5542 | 0.9787 | 0.045* | |
H30C | 0.1885 | 0.4272 | 0.9125 | 0.045* | |
C31 | 0.28375 (14) | 0.3543 (2) | 1.05783 (16) | 0.0327 (6) | |
H31A | 0.2579 | 0.2739 | 1.0279 | 0.049* | |
H31B | 0.2618 | 0.3939 | 1.0983 | 0.049* | |
H31C | 0.3295 | 0.3247 | 1.0906 | 0.049* | |
C32 | 0.32692 (12) | 0.5950 (2) | 1.03564 (15) | 0.0247 (5) | |
O5 | 0.79472 (10) | 0.14643 (17) | 1.07495 (12) | 0.0337 (4) | |
H5O | 0.7542 (17) | 0.182 (3) | 1.057 (2) | 0.053 (10)* | |
C33 | 0.78843 (16) | 0.0039 (3) | 1.0927 (2) | 0.0435 (7) | |
H33A | 0.8305 | −0.0292 | 1.1344 | 0.065* | |
H33B | 0.7789 | −0.0494 | 1.0383 | 0.065* | |
H33C | 0.7515 | −0.0084 | 1.1177 | 0.065* | |
O6 | 0.58651 (13) | 0.1004 (2) | 0.94094 (18) | 0.0795 (9) | |
H6O | 0.617 (2) | 0.172 (4) | 0.963 (2) | 0.081 (12)* | |
C34 | 0.60201 (17) | −0.0223 (3) | 0.98536 (19) | 0.0505 (8) | |
H34A | 0.6385 | −0.0684 | 0.9695 | 0.076* | |
H34B | 0.5622 | −0.0825 | 0.9701 | 0.076* | |
H34C | 0.6165 | −0.0039 | 1.0484 | 0.076* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0324 (9) | 0.0246 (8) | 0.0239 (9) | 0.0001 (7) | 0.0093 (7) | −0.0022 (7) |
O2A | 0.0352 (13) | 0.0173 (10) | 0.0402 (13) | 0.0025 (8) | 0.0121 (10) | 0.0027 (8) |
O3 | 0.0353 (10) | 0.0245 (8) | 0.0248 (9) | 0.0016 (7) | 0.0071 (8) | −0.0030 (7) |
O4 | 0.0383 (10) | 0.0202 (8) | 0.0292 (9) | −0.0012 (7) | 0.0086 (8) | 0.0027 (7) |
N1 | 0.0231 (10) | 0.0193 (9) | 0.0235 (10) | 0.0015 (7) | 0.0092 (8) | −0.0013 (8) |
C1 | 0.0328 (14) | 0.0257 (12) | 0.0354 (14) | 0.0016 (10) | 0.0097 (11) | 0.0016 (10) |
C2 | 0.0392 (16) | 0.0292 (13) | 0.0528 (18) | −0.0046 (11) | 0.0166 (14) | −0.0002 (12) |
C3 | 0.0398 (16) | 0.0337 (14) | 0.0551 (18) | 0.0024 (11) | 0.0243 (14) | 0.0086 (13) |
C4 | 0.0365 (15) | 0.0413 (15) | 0.0380 (15) | 0.0060 (11) | 0.0184 (13) | 0.0035 (12) |
C5 | 0.0284 (13) | 0.0318 (13) | 0.0332 (14) | 0.0026 (10) | 0.0093 (11) | −0.0011 (10) |
C6 | 0.0237 (12) | 0.0226 (11) | 0.0298 (13) | 0.0062 (9) | 0.0075 (10) | 0.0022 (9) |
C7 | 0.0259 (12) | 0.0236 (11) | 0.0250 (12) | 0.0024 (9) | 0.0084 (10) | −0.0020 (9) |
C8 | 0.0242 (12) | 0.0236 (11) | 0.0306 (13) | 0.0020 (9) | 0.0097 (10) | 0.0002 (9) |
C9 | 0.0288 (13) | 0.0296 (12) | 0.0320 (13) | 0.0024 (10) | 0.0087 (11) | −0.0014 (10) |
C10 | 0.0348 (15) | 0.0328 (13) | 0.0350 (14) | 0.0064 (10) | 0.0088 (12) | 0.0053 (11) |
C11 | 0.0367 (15) | 0.0257 (12) | 0.0467 (16) | 0.0083 (10) | 0.0106 (13) | 0.0039 (11) |
C12 | 0.0424 (16) | 0.0275 (13) | 0.0445 (16) | 0.0056 (11) | 0.0069 (13) | −0.0078 (11) |
C13 | 0.0350 (14) | 0.0303 (13) | 0.0324 (14) | 0.0057 (10) | 0.0059 (12) | −0.0030 (10) |
C14 | 0.0254 (12) | 0.0204 (11) | 0.0240 (12) | 0.0014 (8) | 0.0093 (10) | 0.0004 (9) |
C15 | 0.0283 (13) | 0.0209 (11) | 0.0261 (12) | 0.0031 (9) | 0.0077 (10) | 0.0021 (9) |
C16 | 0.0298 (13) | 0.0165 (10) | 0.0290 (13) | −0.0001 (8) | 0.0087 (10) | 0.0004 (9) |
C17 | 0.0275 (13) | 0.0203 (11) | 0.0276 (12) | 0.0020 (9) | 0.0117 (10) | 0.0036 (9) |
C18 | 0.0260 (12) | 0.0203 (11) | 0.0291 (12) | 0.0011 (9) | 0.0110 (10) | 0.0021 (9) |
C19 | 0.0251 (12) | 0.0230 (11) | 0.0242 (12) | 0.0028 (9) | 0.0072 (10) | −0.0018 (9) |
C20 | 0.0243 (12) | 0.0234 (11) | 0.0287 (13) | −0.0001 (9) | 0.0075 (10) | −0.0041 (9) |
C21 | 0.0285 (13) | 0.0210 (11) | 0.0286 (12) | 0.0022 (9) | 0.0104 (10) | −0.0017 (9) |
C22 | 0.0356 (14) | 0.0209 (11) | 0.0391 (15) | −0.0004 (9) | 0.0174 (12) | −0.0019 (10) |
C23 | 0.0366 (14) | 0.0175 (11) | 0.0292 (13) | −0.0014 (9) | 0.0152 (11) | 0.0001 (9) |
C24 | 0.0343 (14) | 0.0195 (11) | 0.0274 (12) | −0.0030 (9) | 0.0129 (11) | −0.0028 (9) |
C25 | 0.0273 (12) | 0.0238 (11) | 0.0255 (12) | −0.0002 (9) | 0.0095 (10) | 0.0003 (9) |
C26 | 0.0317 (13) | 0.0166 (10) | 0.0202 (11) | 0.0031 (8) | 0.0091 (10) | 0.0028 (8) |
C27 | 0.0318 (13) | 0.0212 (11) | 0.0214 (12) | −0.0001 (9) | 0.0070 (10) | −0.0003 (9) |
C28 | 0.0269 (13) | 0.0221 (11) | 0.0320 (13) | −0.0005 (9) | 0.0084 (11) | 0.0009 (10) |
C29 | 0.0330 (13) | 0.0203 (11) | 0.0223 (12) | −0.0002 (9) | 0.0105 (10) | −0.0012 (9) |
C30 | 0.0318 (14) | 0.0286 (12) | 0.0312 (13) | 0.0002 (10) | 0.0114 (11) | −0.0048 (10) |
C31 | 0.0487 (16) | 0.0233 (12) | 0.0295 (13) | −0.0064 (10) | 0.0171 (12) | −0.0015 (10) |
C32 | 0.0277 (13) | 0.0231 (11) | 0.0258 (13) | 0.0015 (9) | 0.0118 (10) | −0.0028 (9) |
O5 | 0.0389 (11) | 0.0283 (9) | 0.0359 (10) | 0.0028 (8) | 0.0144 (9) | 0.0037 (7) |
C33 | 0.0615 (19) | 0.0275 (13) | 0.0516 (17) | 0.0007 (12) | 0.0323 (15) | 0.0006 (12) |
O6 | 0.0642 (16) | 0.0480 (13) | 0.0881 (19) | −0.0280 (11) | −0.0328 (14) | 0.0360 (13) |
C34 | 0.071 (2) | 0.0282 (14) | 0.0420 (17) | −0.0044 (13) | 0.0019 (15) | 0.0015 (12) |
Geometric parameters (Å, º) top
O1—C7 | 1.424 (3) | C17—H17A | 0.9900 |
O1—H1O | 0.93 (3) | C17—H17B | 0.9900 |
O2A—C22 | 1.404 (3) | C18—H18A | 0.9900 |
O2A—H2OA | 0.9161 | C18—H18B | 0.9900 |
O2B—C22 | 1.340 (8) | C19—C20 | 1.516 (3) |
O2B—H2OB | 0.9660 | C19—H19A | 0.9900 |
O3—C32 | 1.253 (3) | C19—H19B | 0.9900 |
O4—C32 | 1.272 (3) | C20—C21 | 1.526 (3) |
N1—C16 | 1.504 (3) | C20—H20A | 0.9900 |
N1—C17 | 1.511 (3) | C20—H20B | 0.9900 |
N1—C19 | 1.514 (3) | C21—C22 | 1.507 (3) |
N1—H1N | 0.92 (3) | C21—H21A | 0.9900 |
C1—C2 | 1.389 (4) | C21—H21B | 0.9900 |
C1—C6 | 1.395 (3) | C22—C23 | 1.515 (3) |
C1—H1 | 0.9500 | C22—H22A | 1.0000 |
C2—C3 | 1.388 (4) | C22—H22B | 1.0000 |
C2—H2 | 0.9500 | C23—C24 | 1.385 (3) |
C3—C4 | 1.386 (4) | C23—C28 | 1.400 (3) |
C3—H3 | 0.9500 | C24—C25 | 1.396 (3) |
C4—C5 | 1.383 (4) | C24—H24 | 0.9500 |
C4—H4 | 0.9500 | C25—C26 | 1.392 (3) |
C5—C6 | 1.395 (3) | C25—H25 | 0.9500 |
C5—H5 | 0.9500 | C26—C27 | 1.398 (3) |
C6—C7 | 1.533 (3) | C26—C29 | 1.533 (3) |
C7—C8 | 1.539 (3) | C27—C28 | 1.389 (3) |
C7—C14 | 1.551 (3) | C27—H27 | 0.9500 |
C8—C9 | 1.393 (3) | C28—H28 | 0.9500 |
C8—C13 | 1.402 (3) | C29—C30 | 1.538 (3) |
C9—C10 | 1.395 (3) | C29—C31 | 1.540 (3) |
C9—H9 | 0.9500 | C29—C32 | 1.558 (3) |
C10—C11 | 1.376 (4) | C30—H30A | 0.9800 |
C10—H10 | 0.9500 | C30—H30B | 0.9800 |
C11—C12 | 1.381 (4) | C30—H30C | 0.9800 |
C11—H11 | 0.9500 | C31—H31A | 0.9800 |
C12—C13 | 1.385 (3) | C31—H31B | 0.9800 |
C12—H12 | 0.9500 | C31—H31C | 0.9800 |
C13—H13 | 0.9500 | O5—C33 | 1.414 (3) |
C14—C15 | 1.528 (3) | O5—H5O | 0.88 (3) |
C14—C18 | 1.532 (3) | C33—H33A | 0.9800 |
C14—H14 | 1.0000 | C33—H33B | 0.9800 |
C15—C16 | 1.519 (3) | C33—H33C | 0.9800 |
C15—H15A | 0.9900 | O6—C34 | 1.365 (3) |
C15—H15B | 0.9900 | O6—H6O | 0.93 (4) |
C16—H16A | 0.9900 | C34—H34A | 0.9800 |
C16—H16B | 0.9900 | C34—H34B | 0.9800 |
C17—C18 | 1.512 (3) | C34—H34C | 0.9800 |
| | | |
C7—O1—H1O | 110.7 (18) | N1—C19—H19A | 108.7 |
C22—O2A—H2OA | 109.3 | C20—C19—H19A | 108.7 |
C22—O2B—H2OB | 109.5 | N1—C19—H19B | 108.7 |
C16—N1—C17 | 110.85 (17) | C20—C19—H19B | 108.7 |
C16—N1—C19 | 111.50 (16) | H19A—C19—H19B | 107.6 |
C17—N1—C19 | 108.08 (17) | C19—C20—C21 | 115.18 (18) |
C16—N1—H1N | 108.1 (16) | C19—C20—H20A | 108.5 |
C17—N1—H1N | 107.1 (16) | C21—C20—H20A | 108.5 |
C19—N1—H1N | 111.1 (16) | C19—C20—H20B | 108.5 |
C2—C1—C6 | 120.6 (2) | C21—C20—H20B | 108.5 |
C2—C1—H1 | 119.7 | H20A—C20—H20B | 107.5 |
C6—C1—H1 | 119.7 | C22—C21—C20 | 112.31 (18) |
C1—C2—C3 | 120.8 (2) | C22—C21—H21A | 109.1 |
C1—C2—H2 | 119.6 | C20—C21—H21A | 109.1 |
C3—C2—H2 | 119.6 | C22—C21—H21B | 109.1 |
C4—C3—C2 | 119.0 (2) | C20—C21—H21B | 109.1 |
C4—C3—H3 | 120.5 | H21A—C21—H21B | 107.9 |
C2—C3—H3 | 120.5 | O2B—C22—C21 | 130.1 (5) |
C5—C4—C3 | 120.2 (2) | O2A—C22—C21 | 112.5 (2) |
C5—C4—H4 | 119.9 | O2B—C22—C23 | 114.0 (5) |
C3—C4—H4 | 119.9 | O2A—C22—C23 | 110.5 (2) |
C4—C5—C6 | 121.4 (2) | C21—C22—C23 | 114.86 (18) |
C4—C5—H5 | 119.3 | O2A—C22—H22A | 106.1 |
C6—C5—H5 | 119.3 | C21—C22—H22A | 106.1 |
C1—C6—C5 | 118.0 (2) | C23—C22—H22A | 106.1 |
C1—C6—C7 | 120.9 (2) | O2B—C22—H22B | 93.4 |
C5—C6—C7 | 121.1 (2) | C21—C22—H22B | 93.4 |
O1—C7—C6 | 106.17 (18) | C23—C22—H22B | 93.4 |
O1—C7—C8 | 110.37 (18) | C24—C23—C28 | 118.0 (2) |
C6—C7—C8 | 110.42 (18) | C24—C23—C22 | 120.5 (2) |
O1—C7—C14 | 109.16 (17) | C28—C23—C22 | 121.5 (2) |
C6—C7—C14 | 109.48 (18) | C23—C24—C25 | 121.1 (2) |
C8—C7—C14 | 111.11 (18) | C23—C24—H24 | 119.5 |
C9—C8—C13 | 117.6 (2) | C25—C24—H24 | 119.5 |
C9—C8—C7 | 120.2 (2) | C26—C25—C24 | 121.2 (2) |
C13—C8—C7 | 122.1 (2) | C26—C25—H25 | 119.4 |
C8—C9—C10 | 121.0 (2) | C24—C25—H25 | 119.4 |
C8—C9—H9 | 119.5 | C25—C26—C27 | 117.6 (2) |
C10—C9—H9 | 119.5 | C25—C26—C29 | 121.1 (2) |
C11—C10—C9 | 120.3 (2) | C27—C26—C29 | 121.12 (19) |
C11—C10—H10 | 119.9 | C28—C27—C26 | 121.2 (2) |
C9—C10—H10 | 119.9 | C28—C27—H27 | 119.4 |
C10—C11—C12 | 119.7 (2) | C26—C27—H27 | 119.4 |
C10—C11—H11 | 120.1 | C27—C28—C23 | 120.9 (2) |
C12—C11—H11 | 120.1 | C27—C28—H28 | 119.6 |
C11—C12—C13 | 120.3 (2) | C23—C28—H28 | 119.6 |
C11—C12—H12 | 119.9 | C26—C29—C30 | 112.49 (18) |
C13—C12—H12 | 119.9 | C26—C29—C31 | 107.94 (18) |
C12—C13—C8 | 121.1 (2) | C30—C29—C31 | 108.8 (2) |
C12—C13—H13 | 119.5 | C26—C29—C32 | 108.22 (18) |
C8—C13—H13 | 119.5 | C30—C29—C32 | 108.76 (18) |
C15—C14—C18 | 107.78 (18) | C31—C29—C32 | 110.70 (18) |
C15—C14—C7 | 113.36 (18) | C29—C30—H30A | 109.5 |
C18—C14—C7 | 112.06 (18) | C29—C30—H30B | 109.5 |
C15—C14—H14 | 107.8 | H30A—C30—H30B | 109.5 |
C18—C14—H14 | 107.8 | C29—C30—H30C | 109.5 |
C7—C14—H14 | 107.8 | H30A—C30—H30C | 109.5 |
C16—C15—C14 | 111.48 (18) | H30B—C30—H30C | 109.5 |
C16—C15—H15A | 109.3 | C29—C31—H31A | 109.5 |
C14—C15—H15A | 109.3 | C29—C31—H31B | 109.5 |
C16—C15—H15B | 109.3 | H31A—C31—H31B | 109.5 |
C14—C15—H15B | 109.3 | C29—C31—H31C | 109.5 |
H15A—C15—H15B | 108.0 | H31A—C31—H31C | 109.5 |
N1—C16—C15 | 112.04 (17) | H31B—C31—H31C | 109.5 |
N1—C16—H16A | 109.2 | O3—C32—O4 | 124.5 (2) |
C15—C16—H16A | 109.2 | O3—C32—C29 | 118.79 (19) |
N1—C16—H16B | 109.2 | O4—C32—C29 | 116.7 (2) |
C15—C16—H16B | 109.2 | C33—O5—H5O | 108 (2) |
H16A—C16—H16B | 107.9 | O5—C33—H33A | 109.5 |
N1—C17—C18 | 112.39 (18) | O5—C33—H33B | 109.5 |
N1—C17—H17A | 109.1 | H33A—C33—H33B | 109.5 |
C18—C17—H17A | 109.1 | O5—C33—H33C | 109.5 |
N1—C17—H17B | 109.1 | H33A—C33—H33C | 109.5 |
C18—C17—H17B | 109.1 | H33B—C33—H33C | 109.5 |
H17A—C17—H17B | 107.9 | C34—O6—H6O | 114 (2) |
C17—C18—C14 | 111.53 (18) | O6—C34—H34A | 109.5 |
C17—C18—H18A | 109.3 | O6—C34—H34B | 109.5 |
C14—C18—H18A | 109.3 | H34A—C34—H34B | 109.5 |
C17—C18—H18B | 109.3 | O6—C34—H34C | 109.5 |
C14—C18—H18B | 109.3 | H34A—C34—H34C | 109.5 |
H18A—C18—H18B | 108.0 | H34B—C34—H34C | 109.5 |
N1—C19—C20 | 114.31 (18) | | |
| | | |
C6—C1—C2—C3 | 0.7 (4) | C19—N1—C17—C18 | −175.62 (17) |
C1—C2—C3—C4 | −0.3 (4) | N1—C17—C18—C14 | 56.6 (2) |
C2—C3—C4—C5 | −0.4 (4) | C15—C14—C18—C17 | −57.6 (2) |
C3—C4—C5—C6 | 0.6 (4) | C7—C14—C18—C17 | 177.05 (18) |
C2—C1—C6—C5 | −0.5 (3) | C16—N1—C19—C20 | 63.2 (2) |
C2—C1—C6—C7 | −178.8 (2) | C17—N1—C19—C20 | −174.76 (17) |
C4—C5—C6—C1 | −0.1 (3) | N1—C19—C20—C21 | 71.4 (2) |
C4—C5—C6—C7 | 178.1 (2) | C19—C20—C21—C22 | −168.4 (2) |
C1—C6—C7—O1 | 2.2 (3) | C20—C21—C22—O2B | −5.6 (7) |
C5—C6—C7—O1 | −176.0 (2) | C20—C21—C22—O2A | 59.4 (3) |
C1—C6—C7—C8 | −117.4 (2) | C20—C21—C22—C23 | −173.0 (2) |
C5—C6—C7—C8 | 64.3 (3) | O2B—C22—C23—C24 | −40.4 (6) |
C1—C6—C7—C14 | 119.9 (2) | O2A—C22—C23—C24 | −102.3 (3) |
C5—C6—C7—C14 | −58.3 (3) | C21—C22—C23—C24 | 129.1 (2) |
O1—C7—C8—C9 | −19.5 (3) | O2B—C22—C23—C28 | 136.2 (6) |
C6—C7—C8—C9 | 97.6 (3) | O2A—C22—C23—C28 | 74.2 (3) |
C14—C7—C8—C9 | −140.7 (2) | C21—C22—C23—C28 | −54.4 (3) |
O1—C7—C8—C13 | 159.4 (2) | C28—C23—C24—C25 | −1.4 (3) |
C6—C7—C8—C13 | −83.6 (3) | C22—C23—C24—C25 | 175.3 (2) |
C14—C7—C8—C13 | 38.1 (3) | C23—C24—C25—C26 | 0.6 (3) |
C13—C8—C9—C10 | −1.4 (4) | C24—C25—C26—C27 | 0.8 (3) |
C7—C8—C9—C10 | 177.5 (2) | C24—C25—C26—C29 | −174.15 (19) |
C8—C9—C10—C11 | 0.6 (4) | C25—C26—C27—C28 | −1.3 (3) |
C9—C10—C11—C12 | 0.9 (4) | C29—C26—C27—C28 | 173.6 (2) |
C10—C11—C12—C13 | −1.5 (4) | C26—C27—C28—C23 | 0.5 (3) |
C11—C12—C13—C8 | 0.7 (4) | C24—C23—C28—C27 | 0.9 (3) |
C9—C8—C13—C12 | 0.8 (4) | C22—C23—C28—C27 | −175.7 (2) |
C7—C8—C13—C12 | −178.1 (2) | C25—C26—C29—C30 | −34.6 (3) |
O1—C7—C14—C15 | −64.3 (2) | C27—C26—C29—C30 | 150.6 (2) |
C6—C7—C14—C15 | 179.91 (17) | C25—C26—C29—C31 | 85.3 (2) |
C8—C7—C14—C15 | 57.7 (2) | C27—C26—C29—C31 | −89.4 (2) |
O1—C7—C14—C18 | 58.0 (2) | C25—C26—C29—C32 | −154.8 (2) |
C6—C7—C14—C18 | −57.8 (2) | C27—C26—C29—C32 | 30.4 (3) |
C8—C7—C14—C18 | 179.96 (19) | C26—C29—C32—O3 | −104.5 (2) |
C18—C14—C15—C16 | 57.9 (2) | C30—C29—C32—O3 | 133.1 (2) |
C7—C14—C15—C16 | −177.52 (17) | C31—C29—C32—O3 | 13.6 (3) |
C17—N1—C16—C15 | 53.3 (2) | C26—C29—C32—O4 | 74.6 (2) |
C19—N1—C16—C15 | 173.75 (18) | C30—C29—C32—O4 | −47.9 (3) |
C14—C15—C16—N1 | −57.3 (2) | C31—C29—C32—O4 | −167.3 (2) |
C16—N1—C17—C18 | −53.2 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O···O5 | 0.93 (3) | 1.86 (3) | 2.763 (2) | 163 (3) |
O2A—H2OA···O6 | 0.92 | 1.80 | 2.680 (3) | 162 |
N1—H1N···O3i | 0.92 (3) | 1.88 (3) | 2.772 (2) | 163 (2) |
O5—H5O···O4i | 0.88 (3) | 1.90 (3) | 2.756 (3) | 166 (3) |
O6—H6O···O4i | 0.93 (4) | 1.74 (4) | 2.666 (3) | 175 (4) |
Symmetry code: (i) −x+1, −y+1, −z+2. |
(II) (±)-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidinium-1-yl]- butyl}phenyl)-2-methylpropionate dihydrate
top
Crystal data top
C32H39NO4·2H2O | F(000) = 1160 |
Mr = 537.67 | Dx = 1.231 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 5703 reflections |
a = 23.8180 (9) Å | θ = 2.2–27.9° |
b = 9.8444 (3) Å | µ = 0.08 mm−1 |
c = 12.3959 (4) Å | T = 110 K |
β = 93.1770 (12)° | Chunk, colourless |
V = 2902.05 (17) Å3 | 0.25 × 0.15 × 0.15 mm |
Z = 4 | |
Data collection top
Nonius KappaCCD area-detector diffractometer | 3243 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.082 |
Graphite monochromator | θmax = 27.9°, θmin = 2.2° |
Detector resolution: 56 microns pixels mm-1 | h = −31→31 |
0.4° ϕ scans | k = −12→12 |
19430 measured reflections | l = −15→16 |
6860 independent reflections | |
Refinement top
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)] = 0.073 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.214 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.99 | w = 1/[σ2(Fo2) + (0.0992P)2 + 0.8167P] where P = (Fo2 + 2Fc2)/3 |
6860 reflections | (Δ/σ)max = 0.004 |
373 parameters | Δρmax = 0.37 e Å−3 |
0 restraints | Δρmin = −0.26 e Å−3 |
Crystal data top
C32H39NO4·2H2O | V = 2902.05 (17) Å3 |
Mr = 537.67 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 23.8180 (9) Å | µ = 0.08 mm−1 |
b = 9.8444 (3) Å | T = 110 K |
c = 12.3959 (4) Å | 0.25 × 0.15 × 0.15 mm |
β = 93.1770 (12)° | |
Data collection top
Nonius KappaCCD area-detector diffractometer | 3243 reflections with I > 2σ(I) |
19430 measured reflections | Rint = 0.082 |
6860 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.073 | 0 restraints |
wR(F2) = 0.214 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.99 | Δρmax = 0.37 e Å−3 |
6860 reflections | Δρmin = −0.26 e Å−3 |
373 parameters | |
Special details top
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. The OH2 group is disordered between two sites with relative occupancies of 57.3 (5)% and 42.7 (5)%. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
O1 | 0.65682 (9) | 0.2288 (2) | 0.02468 (16) | 0.0358 (5) | |
H1O | 0.6791 (19) | 0.160 (5) | 0.032 (4) | 0.091 (16)* | |
O2A | 0.88893 (11) | 0.2721 (3) | 0.6076 (2) | 0.0343 (11) | 0.573 (5) |
H2OA | 0.8707 | 0.3534 | 0.6147 | 0.041* | 0.573 (5) |
O2B | 0.91596 (11) | 0.3884 (3) | 0.5251 (2) | 0.0362 (16) | 0.427 (5) |
H2OB | 0.8915 | 0.4224 | 0.5638 | 0.043* | 0.427 (5) |
O3 | 1.16757 (8) | 0.0061 (2) | 0.84173 (15) | 0.0344 (5) | |
O4 | 1.20251 (9) | 0.1383 (2) | 0.71789 (18) | 0.0450 (6) | |
N1 | 0.79394 (10) | 0.1641 (3) | 0.3159 (2) | 0.0318 (6) | |
H1N | 0.8050 (13) | 0.105 (3) | 0.259 (2) | 0.042 (9)* | |
C1 | 0.65377 (12) | 0.5546 (3) | 0.1509 (3) | 0.0378 (8) | |
H1 | 0.6760 | 0.5394 | 0.2158 | 0.045* | |
C2 | 0.64212 (14) | 0.6877 (4) | 0.1168 (3) | 0.0492 (9) | |
H2 | 0.6570 | 0.7621 | 0.1579 | 0.059* | |
C3 | 0.60912 (15) | 0.7114 (4) | 0.0239 (3) | 0.0528 (10) | |
H3 | 0.6012 | 0.8019 | 0.0009 | 0.063* | |
C4 | 0.58752 (16) | 0.6026 (4) | −0.0358 (3) | 0.0554 (10) | |
H4 | 0.5644 | 0.6186 | −0.0995 | 0.066* | |
C5 | 0.59940 (14) | 0.4710 (3) | −0.0034 (2) | 0.0428 (8) | |
H5 | 0.5845 | 0.3974 | −0.0454 | 0.051* | |
C6 | 0.63311 (12) | 0.4444 (3) | 0.0907 (2) | 0.0330 (7) | |
C7 | 0.64265 (12) | 0.2945 (3) | 0.1219 (2) | 0.0314 (7) | |
C8 | 0.58692 (12) | 0.2385 (3) | 0.1602 (2) | 0.0317 (7) | |
C9 | 0.56465 (12) | 0.2871 (3) | 0.2546 (2) | 0.0374 (7) | |
H9 | 0.5839 | 0.3569 | 0.2946 | 0.045* | |
C10 | 0.51540 (13) | 0.2356 (3) | 0.2910 (3) | 0.0412 (8) | |
H10 | 0.5013 | 0.2694 | 0.3560 | 0.049* | |
C11 | 0.48643 (14) | 0.1352 (4) | 0.2336 (3) | 0.0466 (9) | |
H11 | 0.4525 | 0.0993 | 0.2587 | 0.056* | |
C12 | 0.50754 (14) | 0.0877 (3) | 0.1392 (3) | 0.0468 (9) | |
H12 | 0.4876 | 0.0196 | 0.0984 | 0.056* | |
C13 | 0.55758 (13) | 0.1383 (3) | 0.1031 (2) | 0.0391 (8) | |
H13 | 0.5718 | 0.1037 | 0.0384 | 0.047* | |
C14 | 0.68940 (12) | 0.2750 (3) | 0.2127 (2) | 0.0308 (7) | |
H14 | 0.6809 | 0.3378 | 0.2731 | 0.037* | |
C15 | 0.69294 (12) | 0.1314 (3) | 0.2592 (2) | 0.0314 (7) | |
H15A | 0.6559 | 0.1050 | 0.2849 | 0.038* | |
H15B | 0.7026 | 0.0669 | 0.2018 | 0.038* | |
C16 | 0.73690 (11) | 0.1232 (3) | 0.3519 (2) | 0.0324 (7) | |
H16A | 0.7261 | 0.1838 | 0.4110 | 0.039* | |
H16B | 0.7387 | 0.0291 | 0.3802 | 0.039* | |
C17 | 0.79194 (12) | 0.3052 (3) | 0.2688 (2) | 0.0323 (7) | |
H17A | 0.7828 | 0.3713 | 0.3254 | 0.039* | |
H17B | 0.8292 | 0.3291 | 0.2428 | 0.039* | |
C18 | 0.74792 (11) | 0.3125 (3) | 0.1759 (2) | 0.0306 (7) | |
H18A | 0.7583 | 0.2496 | 0.1179 | 0.037* | |
H18B | 0.7469 | 0.4057 | 0.1458 | 0.037* | |
C19 | 0.83689 (12) | 0.1528 (3) | 0.4088 (2) | 0.0354 (7) | |
H19A | 0.8343 | 0.0614 | 0.4414 | 0.042* | |
H19B | 0.8281 | 0.2204 | 0.4646 | 0.042* | |
C20 | 0.89674 (12) | 0.1756 (3) | 0.3759 (2) | 0.0390 (8) | |
H20A | 0.8995 | 0.2676 | 0.3444 | 0.047* | |
H20B | 0.9052 | 0.1091 | 0.3192 | 0.047* | |
C21 | 0.94075 (12) | 0.1620 (3) | 0.4697 (2) | 0.0369 (7) | |
H21A | 0.9369 | 0.0711 | 0.5027 | 0.044* | |
H21B | 0.9786 | 0.1668 | 0.4407 | 0.044* | |
C22 | 0.93695 (13) | 0.2682 (3) | 0.5570 (3) | 0.0396 (8) | |
H22A | 0.9384 | 0.3570 | 0.5181 | 0.048* | 0.573 (5) |
H22B | 0.9071 | 0.2312 | 0.6024 | 0.048* | 0.427 (5) |
C23 | 0.98852 (12) | 0.2681 (3) | 0.6337 (2) | 0.0337 (7) | |
C24 | 0.99955 (12) | 0.1579 (3) | 0.7028 (2) | 0.0361 (7) | |
H24 | 0.9734 | 0.0850 | 0.7036 | 0.043* | |
C25 | 1.04759 (12) | 0.1533 (3) | 0.7696 (2) | 0.0359 (7) | |
H25 | 1.0535 | 0.0781 | 0.8170 | 0.043* | |
C26 | 1.08800 (12) | 0.2566 (3) | 0.7695 (2) | 0.0296 (7) | |
C27 | 1.07671 (12) | 0.3661 (3) | 0.7012 (2) | 0.0340 (7) | |
H27 | 1.1029 | 0.4388 | 0.6999 | 0.041* | |
C28 | 1.02776 (12) | 0.3714 (3) | 0.6346 (2) | 0.0352 (7) | |
H28 | 1.0212 | 0.4477 | 0.5888 | 0.042* | |
C29 | 1.14214 (12) | 0.2461 (3) | 0.8419 (2) | 0.0311 (7) | |
C30 | 1.17967 (13) | 0.3709 (3) | 0.8371 (3) | 0.0385 (8) | |
H30A | 1.1904 | 0.3847 | 0.7627 | 0.058* | |
H30B | 1.2135 | 0.3575 | 0.8845 | 0.058* | |
H30C | 1.1592 | 0.4508 | 0.8610 | 0.058* | |
C31 | 1.12794 (13) | 0.2225 (3) | 0.9597 (2) | 0.0380 (8) | |
H31A | 1.1054 | 0.2987 | 0.9843 | 0.057* | |
H31B | 1.1628 | 0.2159 | 1.0052 | 0.057* | |
H31C | 1.1065 | 0.1380 | 0.9649 | 0.057* | |
C32 | 1.17373 (12) | 0.1222 (3) | 0.7971 (2) | 0.0319 (7) | |
O5 | 0.74115 (10) | 0.4684 (2) | 0.50036 (18) | 0.0526 (7) | |
H5AO | 0.7737 | 0.4981 | 0.5495 | 0.111 (17)* | |
H5BO | 0.7313 | 0.5502 | 0.4605 | 0.079 (13)* | |
O6 | 0.72081 (11) | 0.7041 (3) | 0.3815 (2) | 0.0588 (7) | |
H6AO | 0.6915 | 0.7708 | 0.4018 | 0.050 (10)* | |
H6BO | 0.7489 | 0.7508 | 0.3447 | 0.082 (14)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0350 (12) | 0.0400 (13) | 0.0329 (11) | 0.0044 (10) | 0.0049 (9) | −0.0045 (10) |
O2A | 0.029 (2) | 0.037 (2) | 0.037 (2) | 0.0024 (15) | 0.0073 (16) | −0.0017 (17) |
O2B | 0.036 (3) | 0.027 (3) | 0.045 (3) | 0.008 (2) | 0.005 (2) | 0.006 (2) |
O3 | 0.0379 (12) | 0.0283 (12) | 0.0369 (11) | 0.0006 (9) | 0.0014 (9) | 0.0034 (10) |
O4 | 0.0487 (14) | 0.0385 (13) | 0.0496 (13) | 0.0044 (10) | 0.0203 (11) | 0.0018 (11) |
N1 | 0.0295 (14) | 0.0326 (15) | 0.0334 (14) | 0.0025 (11) | 0.0034 (11) | 0.0019 (12) |
C1 | 0.0303 (17) | 0.0354 (19) | 0.0477 (19) | 0.0018 (13) | 0.0030 (14) | 0.0037 (16) |
C2 | 0.045 (2) | 0.038 (2) | 0.065 (2) | −0.0011 (16) | 0.0044 (18) | −0.0001 (18) |
C3 | 0.054 (2) | 0.035 (2) | 0.070 (3) | 0.0099 (17) | 0.009 (2) | 0.0139 (19) |
C4 | 0.059 (2) | 0.055 (2) | 0.052 (2) | 0.0065 (19) | −0.0026 (18) | 0.0117 (19) |
C5 | 0.047 (2) | 0.042 (2) | 0.0395 (18) | 0.0032 (15) | −0.0010 (16) | 0.0060 (16) |
C6 | 0.0296 (16) | 0.0326 (18) | 0.0376 (17) | −0.0018 (13) | 0.0085 (13) | 0.0020 (14) |
C7 | 0.0301 (16) | 0.0324 (17) | 0.0323 (16) | 0.0011 (12) | 0.0050 (13) | 0.0002 (14) |
C8 | 0.0294 (16) | 0.0293 (17) | 0.0363 (16) | 0.0025 (12) | 0.0019 (13) | 0.0032 (14) |
C9 | 0.0308 (17) | 0.0346 (18) | 0.0469 (19) | −0.0048 (13) | 0.0045 (14) | −0.0040 (15) |
C10 | 0.0377 (18) | 0.044 (2) | 0.0425 (18) | −0.0020 (15) | 0.0088 (15) | 0.0032 (16) |
C11 | 0.0351 (19) | 0.048 (2) | 0.057 (2) | −0.0090 (16) | 0.0107 (16) | 0.0048 (18) |
C12 | 0.047 (2) | 0.048 (2) | 0.045 (2) | −0.0181 (16) | 0.0026 (16) | 0.0000 (17) |
C13 | 0.0355 (18) | 0.045 (2) | 0.0374 (17) | −0.0043 (15) | 0.0036 (14) | −0.0014 (15) |
C14 | 0.0269 (15) | 0.0330 (17) | 0.0328 (15) | 0.0005 (12) | 0.0048 (12) | 0.0015 (14) |
C15 | 0.0300 (16) | 0.0341 (17) | 0.0306 (15) | −0.0007 (13) | 0.0051 (12) | 0.0012 (14) |
C16 | 0.0285 (16) | 0.0356 (17) | 0.0333 (16) | 0.0006 (13) | 0.0042 (13) | 0.0032 (14) |
C17 | 0.0289 (16) | 0.0279 (17) | 0.0401 (17) | 0.0011 (12) | 0.0038 (13) | 0.0000 (14) |
C18 | 0.0303 (16) | 0.0284 (16) | 0.0335 (16) | −0.0007 (12) | 0.0045 (13) | 0.0023 (13) |
C19 | 0.0346 (17) | 0.0407 (19) | 0.0307 (16) | 0.0004 (14) | 0.0007 (13) | 0.0000 (14) |
C20 | 0.0333 (17) | 0.049 (2) | 0.0342 (17) | 0.0056 (14) | 0.0009 (14) | −0.0103 (15) |
C21 | 0.0289 (16) | 0.0418 (19) | 0.0398 (17) | 0.0057 (13) | 0.0012 (13) | −0.0040 (15) |
C22 | 0.0405 (19) | 0.0389 (19) | 0.0387 (17) | 0.0122 (15) | −0.0040 (15) | −0.0045 (15) |
C23 | 0.0334 (17) | 0.0364 (18) | 0.0311 (16) | 0.0097 (14) | −0.0013 (13) | −0.0054 (14) |
C24 | 0.0316 (17) | 0.0364 (19) | 0.0401 (17) | −0.0023 (13) | −0.0001 (14) | 0.0001 (15) |
C25 | 0.0343 (17) | 0.0352 (18) | 0.0381 (17) | 0.0011 (14) | 0.0014 (14) | 0.0040 (14) |
C26 | 0.0285 (16) | 0.0300 (17) | 0.0307 (15) | 0.0029 (12) | 0.0045 (12) | −0.0013 (13) |
C27 | 0.0373 (17) | 0.0300 (17) | 0.0349 (17) | −0.0004 (13) | 0.0044 (14) | −0.0020 (14) |
C28 | 0.0399 (18) | 0.0298 (17) | 0.0360 (17) | 0.0073 (14) | 0.0029 (14) | 0.0005 (14) |
C29 | 0.0318 (16) | 0.0294 (17) | 0.0320 (16) | −0.0018 (12) | 0.0019 (13) | −0.0007 (13) |
C30 | 0.0391 (18) | 0.0292 (17) | 0.0471 (19) | −0.0027 (14) | 0.0005 (15) | −0.0015 (15) |
C31 | 0.0391 (18) | 0.0398 (19) | 0.0350 (17) | 0.0028 (14) | 0.0015 (14) | −0.0015 (15) |
C32 | 0.0294 (16) | 0.0300 (17) | 0.0362 (17) | −0.0028 (13) | 0.0005 (13) | 0.0019 (15) |
O5 | 0.0608 (16) | 0.0490 (16) | 0.0475 (14) | −0.0143 (12) | −0.0026 (12) | 0.0065 (12) |
O6 | 0.0543 (16) | 0.0555 (16) | 0.0679 (16) | −0.0027 (13) | 0.0143 (13) | 0.0132 (14) |
Geometric parameters (Å, º) top
O1—C7 | 1.425 (3) | C16—H16A | 0.9900 |
O1—H1O | 0.86 (5) | C16—H16B | 0.9900 |
O2A—C22 | 1.335 (4) | C17—C18 | 1.516 (4) |
O2A—H2OA | 0.9167 | C17—H17A | 0.9900 |
O2B—C22 | 1.335 (4) | C17—H17B | 0.9900 |
O2B—H2OB | 0.8445 | C18—H18A | 0.9900 |
O3—C32 | 1.282 (3) | C18—H18B | 0.9900 |
O4—C32 | 1.239 (3) | C19—C20 | 1.521 (4) |
N1—C16 | 1.508 (4) | C19—H19A | 0.9900 |
N1—C19 | 1.501 (4) | C19—H19B | 0.9900 |
N1—C17 | 1.506 (4) | C20—C21 | 1.528 (4) |
N1—H1N | 0.96 (3) | C20—H20A | 0.9900 |
C1—C6 | 1.391 (4) | C20—H20B | 0.9900 |
C1—C2 | 1.400 (4) | C21—C22 | 1.511 (4) |
C1—H1 | 0.9500 | C21—H21A | 0.9900 |
C2—C3 | 1.378 (5) | C21—H21B | 0.9900 |
C2—H2 | 0.9500 | C22—C23 | 1.511 (4) |
C3—C4 | 1.385 (5) | C22—H22A | 1.0000 |
C3—H3 | 0.9500 | C22—H22B | 1.0000 |
C4—C5 | 1.381 (5) | C23—C28 | 1.381 (4) |
C4—H4 | 0.9500 | C23—C24 | 1.398 (4) |
C5—C6 | 1.404 (4) | C24—C25 | 1.376 (4) |
C5—H5 | 0.9500 | C24—H24 | 0.9500 |
C6—C7 | 1.539 (4) | C25—C26 | 1.401 (4) |
C7—C8 | 1.536 (4) | C25—H25 | 0.9500 |
C7—C14 | 1.550 (4) | C26—C27 | 1.387 (4) |
C8—C13 | 1.382 (4) | C26—C29 | 1.533 (4) |
C8—C9 | 1.396 (4) | C27—C28 | 1.392 (4) |
C9—C10 | 1.376 (4) | C27—H27 | 0.9500 |
C9—H9 | 0.9500 | C28—H28 | 0.9500 |
C10—C11 | 1.381 (5) | C29—C30 | 1.523 (4) |
C10—H10 | 0.9500 | C29—C31 | 1.535 (4) |
C11—C12 | 1.381 (5) | C29—C32 | 1.552 (4) |
C11—H11 | 0.9500 | C30—H30A | 0.9800 |
C12—C13 | 1.389 (4) | C30—H30B | 0.9800 |
C12—H12 | 0.9500 | C30—H30C | 0.9800 |
C13—H13 | 0.9500 | C31—H31A | 0.9800 |
C14—C15 | 1.527 (4) | C31—H31B | 0.9800 |
C14—C18 | 1.536 (4) | C31—H31C | 0.9800 |
C14—H14 | 1.0000 | O5—H5AO | 1.0021 |
C15—C16 | 1.514 (4) | O5—H5BO | 0.9672 |
C15—H15A | 0.9900 | O6—H6AO | 1.0011 |
C15—H15B | 0.9900 | O6—H6BO | 0.9502 |
| | | |
C7—O1—H1O | 117 (3) | C17—C18—H18A | 109.4 |
C22—O2A—H2OA | 119.5 | C14—C18—H18A | 109.4 |
C22—O2B—H2OB | 116.2 | C17—C18—H18B | 109.4 |
C16—N1—C19 | 109.9 (2) | C14—C18—H18B | 109.4 |
C16—N1—C17 | 110.6 (2) | H18A—C18—H18B | 108.0 |
C19—N1—C17 | 111.8 (2) | N1—C19—C20 | 113.1 (2) |
C16—N1—H1N | 110.1 (18) | N1—C19—H19A | 109.0 |
C19—N1—H1N | 108.4 (18) | C20—C19—H19A | 109.0 |
C17—N1—H1N | 106.1 (18) | N1—C19—H19B | 109.0 |
C6—C1—C2 | 120.7 (3) | C20—C19—H19B | 109.0 |
C6—C1—H1 | 119.7 | H19A—C19—H19B | 107.8 |
C2—C1—H1 | 119.7 | C19—C20—C21 | 113.4 (2) |
C3—C2—C1 | 120.4 (3) | C19—C20—H20A | 108.9 |
C3—C2—H2 | 119.8 | C21—C20—H20A | 108.9 |
C1—C2—H2 | 119.8 | C19—C20—H20B | 108.9 |
C2—C3—C4 | 119.6 (3) | C21—C20—H20B | 108.9 |
C2—C3—H3 | 120.2 | H20A—C20—H20B | 107.7 |
C4—C3—H3 | 120.2 | C22—C21—C20 | 114.7 (3) |
C5—C4—C3 | 120.4 (3) | C22—C21—H21A | 108.6 |
C5—C4—H4 | 119.8 | C20—C21—H21A | 108.6 |
C3—C4—H4 | 119.8 | C22—C21—H21B | 108.6 |
C4—C5—C6 | 121.0 (3) | C20—C21—H21B | 108.6 |
C4—C5—H5 | 119.5 | H21A—C21—H21B | 107.6 |
C6—C5—H5 | 119.5 | O2A—C22—C21 | 116.3 (3) |
C1—C6—C5 | 118.0 (3) | O2B—C22—C21 | 115.9 (3) |
C1—C6—C7 | 124.7 (3) | O2A—C22—C23 | 113.1 (3) |
C5—C6—C7 | 117.2 (3) | O2B—C22—C23 | 117.7 (3) |
O1—C7—C6 | 105.1 (2) | C21—C22—C23 | 111.8 (2) |
O1—C7—C8 | 110.4 (2) | O2A—C22—H22A | 104.8 |
C6—C7—C8 | 107.7 (2) | C21—C22—H22A | 104.8 |
O1—C7—C14 | 111.3 (2) | C23—C22—H22A | 104.8 |
C6—C7—C14 | 113.0 (2) | O2B—C22—H22B | 102.9 |
C8—C7—C14 | 109.2 (2) | C21—C22—H22B | 102.9 |
C13—C8—C9 | 118.0 (3) | C23—C22—H22B | 102.9 |
C13—C8—C7 | 121.3 (3) | C28—C23—C24 | 117.5 (3) |
C9—C8—C7 | 120.7 (3) | C28—C23—C22 | 122.0 (3) |
C10—C9—C8 | 121.3 (3) | C24—C23—C22 | 120.3 (3) |
C10—C9—H9 | 119.4 | C25—C24—C23 | 121.1 (3) |
C8—C9—H9 | 119.4 | C25—C24—H24 | 119.5 |
C9—C10—C11 | 120.4 (3) | C23—C24—H24 | 119.5 |
C9—C10—H10 | 119.8 | C24—C25—C26 | 121.6 (3) |
C11—C10—H10 | 119.8 | C24—C25—H25 | 119.2 |
C10—C11—C12 | 119.0 (3) | C26—C25—H25 | 119.2 |
C10—C11—H11 | 120.5 | C27—C26—C25 | 117.1 (3) |
C12—C11—H11 | 120.5 | C27—C26—C29 | 122.6 (3) |
C11—C12—C13 | 120.7 (3) | C25—C26—C29 | 120.4 (3) |
C11—C12—H12 | 119.6 | C26—C27—C28 | 121.2 (3) |
C13—C12—H12 | 119.6 | C26—C27—H27 | 119.4 |
C12—C13—C8 | 120.6 (3) | C28—C27—H27 | 119.4 |
C12—C13—H13 | 119.7 | C23—C28—C27 | 121.4 (3) |
C8—C13—H13 | 119.7 | C23—C28—H28 | 119.3 |
C15—C14—C18 | 107.6 (2) | C27—C28—H28 | 119.3 |
C15—C14—C7 | 114.2 (2) | C30—C29—C26 | 113.5 (2) |
C18—C14—C7 | 112.4 (2) | C30—C29—C31 | 108.7 (2) |
C15—C14—H14 | 107.4 | C26—C29—C31 | 110.2 (2) |
C18—C14—H14 | 107.4 | C30—C29—C32 | 108.8 (2) |
C7—C14—H14 | 107.4 | C26—C29—C32 | 104.6 (2) |
C16—C15—C14 | 110.9 (2) | C31—C29—C32 | 111.0 (2) |
C16—C15—H15A | 109.5 | C29—C30—H30A | 109.5 |
C14—C15—H15A | 109.5 | C29—C30—H30B | 109.5 |
C16—C15—H15B | 109.5 | H30A—C30—H30B | 109.5 |
C14—C15—H15B | 109.5 | C29—C30—H30C | 109.5 |
H15A—C15—H15B | 108.0 | H30A—C30—H30C | 109.5 |
N1—C16—C15 | 111.0 (2) | H30B—C30—H30C | 109.5 |
N1—C16—H16A | 109.4 | C29—C31—H31A | 109.5 |
C15—C16—H16A | 109.4 | C29—C31—H31B | 109.5 |
N1—C16—H16B | 109.4 | H31A—C31—H31B | 109.5 |
C15—C16—H16B | 109.4 | C29—C31—H31C | 109.5 |
H16A—C16—H16B | 108.0 | H31A—C31—H31C | 109.5 |
C18—C17—N1 | 110.1 (2) | H31B—C31—H31C | 109.5 |
C18—C17—H17A | 109.6 | O4—C32—O3 | 122.6 (3) |
N1—C17—H17A | 109.6 | O4—C32—C29 | 118.9 (3) |
C18—C17—H17B | 109.6 | O3—C32—C29 | 118.5 (2) |
N1—C17—H17B | 109.6 | H5AO—O5—H5BO | 103.0 |
H17A—C17—H17B | 108.1 | H6AO—O6—H6BO | 108.8 |
C17—C18—C14 | 111.3 (2) | | |
| | | |
C6—C1—C2—C3 | 1.1 (5) | C19—N1—C17—C18 | −179.7 (2) |
C1—C2—C3—C4 | 0.0 (5) | N1—C17—C18—C14 | 58.8 (3) |
C2—C3—C4—C5 | −0.7 (5) | C15—C14—C18—C17 | −58.6 (3) |
C3—C4—C5—C6 | 0.5 (5) | C7—C14—C18—C17 | 174.7 (2) |
C2—C1—C6—C5 | −1.4 (4) | C16—N1—C19—C20 | 173.0 (2) |
C2—C1—C6—C7 | −179.0 (3) | C17—N1—C19—C20 | −63.9 (3) |
C4—C5—C6—C1 | 0.6 (5) | N1—C19—C20—C21 | −179.0 (3) |
C4—C5—C6—C7 | 178.4 (3) | C19—C20—C21—C22 | −65.2 (4) |
C1—C6—C7—O1 | −135.5 (3) | C20—C21—C22—O2A | 60.6 (4) |
C5—C6—C7—O1 | 46.9 (3) | C20—C21—C22—O2B | −28.8 (4) |
C1—C6—C7—C8 | 106.9 (3) | C20—C21—C22—C23 | −167.5 (3) |
C5—C6—C7—C8 | −70.7 (3) | O2A—C22—C23—C28 | −117.8 (3) |
C1—C6—C7—C14 | −13.9 (4) | O2B—C22—C23—C28 | −29.3 (4) |
C5—C6—C7—C14 | 168.5 (3) | C21—C22—C23—C28 | 108.6 (3) |
O1—C7—C8—C13 | 0.0 (4) | O2A—C22—C23—C24 | 65.7 (4) |
C6—C7—C8—C13 | 114.3 (3) | O2B—C22—C23—C24 | 154.3 (3) |
C14—C7—C8—C13 | −122.7 (3) | C21—C22—C23—C24 | −67.8 (4) |
O1—C7—C8—C9 | 179.6 (3) | C28—C23—C24—C25 | 0.4 (4) |
C6—C7—C8—C9 | −66.2 (3) | C22—C23—C24—C25 | 177.0 (3) |
C14—C7—C8—C9 | 56.9 (4) | C23—C24—C25—C26 | −1.5 (5) |
C13—C8—C9—C10 | 1.0 (5) | C24—C25—C26—C27 | 1.8 (4) |
C7—C8—C9—C10 | −178.6 (3) | C24—C25—C26—C29 | −177.7 (3) |
C8—C9—C10—C11 | −0.8 (5) | C25—C26—C27—C28 | −1.0 (4) |
C9—C10—C11—C12 | −0.2 (5) | C29—C26—C27—C28 | 178.5 (3) |
C10—C11—C12—C13 | 1.0 (5) | C24—C23—C28—C27 | 0.4 (4) |
C11—C12—C13—C8 | −0.8 (5) | C22—C23—C28—C27 | −176.1 (3) |
C9—C8—C13—C12 | −0.2 (5) | C26—C27—C28—C23 | 0.0 (4) |
C7—C8—C13—C12 | 179.4 (3) | C27—C26—C29—C30 | 4.1 (4) |
O1—C7—C14—C15 | −72.1 (3) | C25—C26—C29—C30 | −176.4 (3) |
C6—C7—C14—C15 | 169.9 (2) | C27—C26—C29—C31 | 126.2 (3) |
C8—C7—C14—C15 | 50.0 (3) | C25—C26—C29—C31 | −54.3 (3) |
O1—C7—C14—C18 | 50.9 (3) | C27—C26—C29—C32 | −114.4 (3) |
C6—C7—C14—C18 | −67.1 (3) | C25—C26—C29—C32 | 65.1 (3) |
C8—C7—C14—C18 | 173.1 (2) | C30—C29—C32—O4 | −39.1 (4) |
C18—C14—C15—C16 | 58.1 (3) | C26—C29—C32—O4 | 82.5 (3) |
C7—C14—C15—C16 | −176.3 (2) | C31—C29—C32—O4 | −158.7 (3) |
C19—N1—C16—C15 | −179.1 (2) | C30—C29—C32—O3 | 143.0 (3) |
C17—N1—C16—C15 | 57.1 (3) | C26—C29—C32—O3 | −95.4 (3) |
C14—C15—C16—N1 | −58.6 (3) | C31—C29—C32—O3 | 23.4 (4) |
C16—N1—C17—C18 | −56.9 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O···O5i | 0.86 (5) | 2.00 (5) | 2.822 (3) | 160 (4) |
O2A—H2OA···O3ii | 0.92 | 1.85 | 2.758 (3) | 168 |
O2B—H2OB···O3ii | 0.84 | 2.05 | 2.897 (3) | 180 |
N1—H1N···O3iii | 0.96 (3) | 1.81 (3) | 2.768 (3) | 174 (3) |
O5—H5AO···O3ii | 1.00 | 1.89 | 2.868 (3) | 164 |
O5—H5BO···O6 | 0.97 | 1.81 | 2.776 (3) | 174 |
O6—H6BO···O4iv | 0.95 | 1.80 | 2.741 (3) | 172 |
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+2, y+1/2, −z+3/2; (iii) −x+2, −y, −z+1; (iv) −x+2, −y+1, −z+1. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C32H39NO4·2CH4O | C32H39NO4·2H2O |
Mr | 565.73 | 537.67 |
Crystal system, space group | Monoclinic, P21/c | Monoclinic, P21/c |
Temperature (K) | 110 | 110 |
a, b, c (Å) | 20.8661 (3), 9.6138 (2), 16.0702 (5) | 23.8180 (9), 9.8444 (3), 12.3959 (4) |
β (°) | 107.8870 (8) | 93.1770 (12) |
V (Å3) | 3067.90 (12) | 2902.05 (17) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.08 | 0.08 |
Crystal size (mm) | 0.30 × 0.25 × 0.25 | 0.25 × 0.15 × 0.15 |
|
Data collection |
Diffractometer | Nonius KappaCCD area-detector diffractometer | Nonius KappaCCD area-detector diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 22588, 7172, 4405 | 19430, 6860, 3243 |
Rint | 0.072 | 0.082 |
(sin θ/λ)max (Å−1) | 0.658 | 0.658 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.064, 0.168, 1.00 | 0.073, 0.214, 0.99 |
No. of reflections | 7172 | 6860 |
No. of parameters | 396 | 373 |
No. of restraints | 3 | 0 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.42, −0.41 | 0.37, −0.26 |
Selected torsion angles (º) for (I) topO1—C7—C14—C15 | −64.3 (2) | C20—C21—C22—O2A | 59.4 (3) |
O1—C7—C14—C18 | 58.0 (2) | C20—C21—C22—C23 | −173.0 (2) |
N1—C19—C20—C21 | 71.4 (2) | C25—C26—C29—C32 | −154.8 (2) |
C19—C20—C21—C22 | −168.4 (2) | C27—C26—C29—C32 | 30.4 (3) |
C20—C21—C22—O2B | −5.6 (7) | | |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O···O5 | 0.93 (3) | 1.86 (3) | 2.763 (2) | 163 (3) |
O2A—H2OA···O6 | 0.92 | 1.80 | 2.680 (3) | 162 |
N1—H1N···O3i | 0.92 (3) | 1.88 (3) | 2.772 (2) | 163 (2) |
O5—H5O···O4i | 0.88 (3) | 1.90 (3) | 2.756 (3) | 166 (3) |
O6—H6O···O4i | 0.93 (4) | 1.74 (4) | 2.666 (3) | 175 (4) |
Symmetry code: (i) −x+1, −y+1, −z+2. |
Selected torsion angles (º) for (II) topO1—C7—C14—C15 | −72.1 (3) | C20—C21—C22—O2B | −28.8 (4) |
O1—C7—C14—C18 | 50.9 (3) | C20—C21—C22—C23 | −167.5 (3) |
N1—C19—C20—C21 | −179.0 (3) | C27—C26—C29—C32 | −114.4 (3) |
C19—C20—C21—C22 | −65.2 (4) | C25—C26—C29—C32 | 65.1 (3) |
C20—C21—C22—O2A | 60.6 (4) | | |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1O···O5i | 0.86 (5) | 2.00 (5) | 2.822 (3) | 160 (4) |
O2A—H2OA···O3ii | 0.92 | 1.85 | 2.758 (3) | 168 |
O2B—H2OB···O3ii | 0.84 | 2.05 | 2.897 (3) | 180 |
N1—H1N···O3iii | 0.96 (3) | 1.81 (3) | 2.768 (3) | 174 (3) |
O5—H5AO···O3ii | 1.00 | 1.89 | 2.868 (3) | 164 |
O5—H5BO···O6 | 0.97 | 1.81 | 2.776 (3) | 174 |
O6—H6BO···O4iv | 0.95 | 1.80 | 2.741 (3) | 172 |
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+2, y+1/2, −z+3/2; (iii) −x+2, −y, −z+1; (iv) −x+2, −y+1, −z+1. |
We have been investigating the structural chemistry and pseudo-polymorphism of a series of pharmaceutical compounds (Tessler & Goldberg, 2004a,b, 2005a,b). Fexofenadine is an antihistamine used to relieve hay fever and allergy symptoms. The drug is administered orally in its hydrochloride form as the active ingredient. Fexofenadine was approved by the US Food and Drug Administration in July 1995. It works by preventing the activation of H1-receptor-containing cells by histamine, a chemical which is released in the body by other cells. Fexofenadine (L) contains several functional groups with hydrogen-bonding capacity, and normally exists as a zwitterion. Therefore, not surprisingly, it forms sizeable single crystals more readily in a solvated (with polar and protic solvents) rather than a pure form, as co-crystallization with protic solvents allows for better (strain free) optimization of the hydrogen-bonding potential (Etter, 1991).
The conformational flexibility of L aids in the formation of pseudo-polymorphic crystals of this compound. In this context, we were able to crystallize and analyze (at ca 110 K) the structures of the methanol disolvate, (I), and the dihydrate, (II), of L. The corresponding molecular structures are illustrated in Fig. 1, showing the different conformations of the molecular framework.
The main conformational degrees of freedom of the fexofenadine framework are about the C7—C14 and C26—C29 single bonds, and atoms C19–C22 in the central aliphatic chain (Tables 1 and 3). Inspection of the torsion angles indicates a minor difference between the two structures in the conformation about the C7—C14 bond. More significant variation is associated with the rotation of the α,α-dimethyl acetic acid residue with respect to the adjacent phenyl ring in (I) and (II), in order to optimize the corresponding intermolecular interaction scheme (see below). However, the most distinct flexibility is apparent in the N1—C19—C20—C21 and C19—C20—C21—C22 torsion angles (Tables 1 and 3). They impart a bent molecular framework structure in (I), as opposed to a more extended conformation in (II). The disorder of the O2—H functions, with C20—C21—C22—O2A torsion angles of 59.4 (3)° in (I) and 60.6 (4)° in (II) at the major site, but with C20—C21—C22—O2B torsion angles of −5.6 (7)° in (I) and −28.8 (4)° in (II) at the minor site, further attests to the conformational flexibility of L.
The above conformational details (Tables 1 and 3) are closely related to the intermolecular interaction patterns revealed by the two crystals. The most dominant intermolecular interaction in both structures is the charge-assisted hydrogen-bonding attraction between the NH+ and the COO− sites of adjacent molecules (Jeffrey, 1997). This leads to the the formation of dimeric entities paired by two NH+···COO− hydrogen bonds between molecules related to each other by crystallographic inversion (Tables 2 and 4).
In (I), the two methanol molecules incorporated into the lattice provide the solvation environment as H-atom acceptors for the two hydroxylic acid functions O1—H and O2—H (disordered as O2A and O2B), which point to the concave side of the paired molecules, by hydrogen bonding (Table 2). Each methanol species also solvates the carboxylate function by donating its H atom to the second carboxylate O atom (O4). The hydrogen-bonded clusters in this structure consist of two molecules of fexofenadine and four molecules of methanol, and have an oval shape (Fig. 2, Table 2). The crystal packing of these discrete hydrogen-bonded clusters in (I) is stabilized by common dispersion between their lipophilic C—H lined surfaces.
While similar NH+···COO− bound dimers form in structure (II) around inversion centres, the different conformation of the fexofenadine framework causes the O2—H site to point outward and be exposed on the periphery of the dimeric entities to hydrogen-bonding interaction with neighbouring dimers (Fig. 3). This results in the formation of an extended hydrogen-bonding pattern that propagates continuously throughout the crystal within molecular layers perpendicular to the a axis and centered at x = 0 (Fig. 4). The water molecules incorporated into (II) take part in the solvation of one of the hydroxylic acid functions (O1—H) and of the carboxylate anion. In this structure, the fexofenadine dimers are interlinked with neighbouring dimeric entities by four additional hydrogen bonds, utilizing to this end the disordered O2—H H-atom donors and the COO− H-atom acceptors (Table 4). The crystal packing of the hydrogen-bonded layers in (II) is illustrated in Fig. 4.
All bond lengths and angles are in normal ranges (Reference for standard values?), including indication of partial delocalization of the electron density within the C32—O3 and C32—O4 bonds of the carboxylate group, which is consistent with the zwitterionic nature of L. To the authors' knowledge, this is the first crystallographic report of the fexofenadine structure (Cambridge Structural Database, Version?; Allen, 2002).