Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270112041583/fg3275sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270112041583/fg3275Isup2.hkl |
CCDC reference: 914651
The title compound was obtained according to the synthesis described by Vincent et al. (1982) and Robert et al. (1984). Recrystallization from a solution in a water–ethanol mixture (1:1 v/v) at room temperature over one month afforded colourless prismatic crystals of (I).H2O.
H atoms were located in difference Fourier maps and subsequently geometrically optimized and allowed for as riding atoms, with C—H = 1.00 for methine, 0.99 for methylene and 0.98 Å for methyl groups, and with Uiso(H) = 1.2Ueq(C) for methine and methylene H atoms or 1.5Ueq(C) for methyl H atoms. H atoms bonded to N or O atoms (including water molecules) were refined freely.
Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).
C17H28N2O5·H2O | F(000) = 776 |
Mr = 358.43 | Dx = 1.253 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 9990 reflections |
a = 8.1645 (2) Å | θ = 3.8–67.7° |
b = 10.0136 (2) Å | µ = 0.78 mm−1 |
c = 23.2429 (5) Å | T = 100 K |
V = 1900.25 (7) Å3 | Prism, colourless |
Z = 4 | 0.30 × 0.25 × 0.20 mm |
Bruker APEXII CCD area-detector diffractometer | 3321 independent reflections |
Radiation source: 30W microsource with MonoCap capillary | 3304 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.026 |
ω scans | θmax = 66.0°, θmin = 3.8° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −9→9 |
Tmin = 0.799, Tmax = 0.859 | k = −11→10 |
19011 measured reflections | l = −27→27 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.027 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.069 | w = 1/[σ2(Fo2) + (0.0354P)2 + 0.4207P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max = 0.001 |
3321 reflections | Δρmax = 0.17 e Å−3 |
248 parameters | Δρmin = −0.15 e Å−3 |
0 restraints | Absolute structure: Flack (1983), with 1396 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.04 (14) |
C17H28N2O5·H2O | V = 1900.25 (7) Å3 |
Mr = 358.43 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 8.1645 (2) Å | µ = 0.78 mm−1 |
b = 10.0136 (2) Å | T = 100 K |
c = 23.2429 (5) Å | 0.30 × 0.25 × 0.20 mm |
Bruker APEXII CCD area-detector diffractometer | 3321 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 3304 reflections with I > 2σ(I) |
Tmin = 0.799, Tmax = 0.859 | Rint = 0.026 |
19011 measured reflections |
R[F2 > 2σ(F2)] = 0.027 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.069 | Δρmax = 0.17 e Å−3 |
S = 1.08 | Δρmin = −0.15 e Å−3 |
3321 reflections | Absolute structure: Flack (1983), with 1396 Friedel pairs |
248 parameters | Absolute structure parameter: 0.04 (14) |
0 restraints |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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 | ||
O1 | 1.19141 (11) | 0.77807 (9) | 0.81604 (4) | 0.0234 (3) | |
O2 | 0.81043 (12) | 0.73189 (10) | 0.96914 (4) | 0.0267 (3) | |
O3 | 0.74520 (11) | 0.57632 (10) | 0.90423 (4) | 0.0271 (3) | |
O4 | 1.14302 (11) | 1.05823 (9) | 0.73988 (4) | 0.0258 (3) | |
O5 | 1.12231 (12) | 0.91004 (10) | 0.66751 (4) | 0.0256 (3) | |
N1 | 0.95001 (13) | 0.88641 (11) | 0.80975 (4) | 0.0188 (3) | |
N2 | 1.13397 (14) | 0.73600 (11) | 0.93327 (5) | 0.0202 (3) | |
C1 | 0.95227 (16) | 0.87467 (13) | 0.74669 (5) | 0.0203 (4) | |
C2 | 0.78361 (16) | 0.92720 (15) | 0.72808 (5) | 0.0243 (4) | |
C3 | 0.67608 (16) | 0.90273 (14) | 0.78116 (6) | 0.0226 (4) | |
C4 | 0.51274 (16) | 0.97735 (16) | 0.78149 (6) | 0.0298 (4) | |
C5 | 0.52798 (18) | 1.12478 (16) | 0.79661 (7) | 0.0351 (5) | |
C6 | 0.62553 (18) | 1.14382 (14) | 0.85218 (7) | 0.0319 (4) | |
C7 | 0.79826 (17) | 1.08739 (13) | 0.84432 (6) | 0.0259 (4) | |
C8 | 0.79096 (15) | 0.93817 (13) | 0.83136 (5) | 0.0194 (3) | |
C9 | 1.07581 (15) | 0.83683 (12) | 0.83935 (5) | 0.0190 (3) | |
C10 | 1.07867 (15) | 0.86178 (13) | 0.90427 (5) | 0.0206 (3) | |
C11 | 1.02815 (16) | 0.61545 (13) | 0.92251 (5) | 0.0203 (3) | |
C12 | 1.08206 (18) | 0.50005 (14) | 0.96119 (6) | 0.0275 (4) | |
C13 | 1.2594 (2) | 0.45466 (17) | 0.95242 (7) | 0.0361 (5) | |
C14 | 1.2974 (2) | 0.32644 (17) | 0.98464 (8) | 0.0450 (6) | |
C15 | 1.08629 (15) | 0.95782 (13) | 0.71945 (6) | 0.0205 (3) | |
C16 | 1.19887 (18) | 0.97438 (14) | 0.91845 (6) | 0.0276 (4) | |
C17 | 0.84528 (16) | 0.64538 (13) | 0.93266 (5) | 0.0202 (3) | |
O1W | 1.45303 (14) | 0.71407 (13) | 0.89105 (5) | 0.0389 (3) | |
H1 | 0.96460 | 0.77890 | 0.73520 | 0.0240* | |
H2NB | 1.145 (2) | 0.7501 (16) | 0.9706 (8) | 0.029 (4)* | |
H2NA | 1.243 (2) | 0.7151 (17) | 0.9209 (7) | 0.030 (4)* | |
H2A | 0.78860 | 1.02350 | 0.71850 | 0.0290* | |
H2B | 0.74180 | 0.87740 | 0.69430 | 0.0290* | |
H3 | 0.65210 | 0.80490 | 0.78330 | 0.0270* | |
H4A | 0.43870 | 0.93410 | 0.80960 | 0.0360* | |
H4B | 0.46180 | 0.96930 | 0.74300 | 0.0360* | |
H5A | 0.41730 | 1.16370 | 0.80130 | 0.0420* | |
H5B | 0.58340 | 1.17250 | 0.76480 | 0.0420* | |
H5O | 1.180 (2) | 0.971 (2) | 0.6484 (9) | 0.044 (5)* | |
H6A | 0.56990 | 1.09720 | 0.88430 | 0.0380* | |
H6B | 0.63180 | 1.24000 | 0.86180 | 0.0380* | |
H7A | 0.86280 | 1.10250 | 0.87980 | 0.0310* | |
H7B | 0.85360 | 1.13440 | 0.81230 | 0.0310* | |
H8 | 0.75760 | 0.88800 | 0.86670 | 0.0230* | |
H10 | 0.96640 | 0.88620 | 0.91790 | 0.0250* | |
H11 | 1.04260 | 0.58750 | 0.88150 | 0.0240* | |
H12A | 1.00870 | 0.42300 | 0.95420 | 0.0330* | |
H12B | 1.06800 | 0.52740 | 1.00180 | 0.0330* | |
H13A | 1.27940 | 0.44070 | 0.91080 | 0.0430* | |
H13B | 1.33430 | 0.52590 | 0.96580 | 0.0430* | |
H14A | 1.22450 | 0.25530 | 0.97120 | 0.0680* | |
H14B | 1.28070 | 0.34050 | 1.02600 | 0.0680* | |
H14C | 1.41150 | 0.30080 | 0.97760 | 0.0680* | |
H16A | 1.31020 | 0.94670 | 0.90810 | 0.0410* | |
H16B | 1.19410 | 0.99410 | 0.95970 | 0.0410* | |
H16C | 1.16930 | 1.05450 | 0.89660 | 0.0410* | |
H1W | 1.538 (3) | 0.658 (2) | 0.8949 (9) | 0.052 (6)* | |
H2W | 1.436 (3) | 0.717 (2) | 0.8567 (10) | 0.059 (7)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0188 (4) | 0.0282 (5) | 0.0232 (4) | 0.0040 (4) | 0.0021 (4) | 0.0033 (4) |
O2 | 0.0275 (5) | 0.0316 (5) | 0.0211 (4) | −0.0010 (4) | 0.0060 (4) | −0.0047 (4) |
O3 | 0.0187 (4) | 0.0330 (5) | 0.0296 (5) | −0.0006 (4) | 0.0012 (4) | −0.0080 (4) |
O4 | 0.0210 (5) | 0.0241 (5) | 0.0324 (5) | −0.0029 (4) | 0.0002 (4) | 0.0002 (4) |
O5 | 0.0268 (5) | 0.0268 (5) | 0.0232 (4) | −0.0001 (4) | 0.0049 (4) | 0.0048 (4) |
N1 | 0.0162 (5) | 0.0222 (5) | 0.0179 (5) | 0.0001 (4) | 0.0005 (4) | 0.0018 (4) |
N2 | 0.0201 (5) | 0.0246 (6) | 0.0159 (5) | 0.0011 (5) | −0.0028 (4) | 0.0003 (4) |
C1 | 0.0210 (7) | 0.0220 (6) | 0.0179 (6) | −0.0001 (5) | −0.0004 (5) | 0.0016 (5) |
C2 | 0.0191 (6) | 0.0332 (7) | 0.0207 (6) | −0.0035 (6) | −0.0029 (5) | 0.0045 (5) |
C3 | 0.0174 (6) | 0.0278 (7) | 0.0226 (6) | −0.0036 (5) | −0.0015 (5) | 0.0058 (5) |
C4 | 0.0150 (6) | 0.0440 (8) | 0.0304 (7) | −0.0024 (6) | −0.0020 (6) | 0.0111 (6) |
C5 | 0.0193 (7) | 0.0397 (8) | 0.0462 (9) | 0.0087 (6) | 0.0046 (6) | 0.0167 (7) |
C6 | 0.0246 (7) | 0.0262 (7) | 0.0450 (8) | 0.0049 (6) | 0.0082 (6) | 0.0025 (6) |
C7 | 0.0183 (6) | 0.0255 (7) | 0.0339 (7) | 0.0002 (5) | 0.0020 (6) | −0.0010 (6) |
C8 | 0.0134 (6) | 0.0244 (6) | 0.0203 (6) | 0.0001 (5) | 0.0003 (5) | 0.0029 (5) |
C9 | 0.0165 (6) | 0.0178 (6) | 0.0228 (6) | −0.0029 (5) | 0.0003 (5) | 0.0032 (5) |
C10 | 0.0189 (6) | 0.0222 (6) | 0.0206 (6) | 0.0008 (5) | −0.0024 (5) | 0.0012 (5) |
C11 | 0.0205 (6) | 0.0235 (6) | 0.0168 (6) | −0.0016 (5) | −0.0015 (5) | −0.0003 (5) |
C12 | 0.0299 (7) | 0.0254 (7) | 0.0271 (7) | 0.0010 (6) | −0.0027 (6) | 0.0034 (5) |
C13 | 0.0359 (8) | 0.0372 (8) | 0.0353 (8) | 0.0080 (7) | −0.0039 (7) | 0.0040 (6) |
C14 | 0.0489 (10) | 0.0361 (9) | 0.0501 (10) | 0.0098 (8) | −0.0089 (8) | 0.0028 (7) |
C15 | 0.0168 (6) | 0.0226 (6) | 0.0222 (6) | 0.0043 (5) | −0.0005 (5) | 0.0046 (5) |
C16 | 0.0281 (7) | 0.0256 (7) | 0.0291 (7) | −0.0034 (6) | −0.0052 (6) | −0.0001 (5) |
C17 | 0.0238 (6) | 0.0220 (6) | 0.0148 (5) | 0.0002 (5) | 0.0037 (5) | 0.0033 (5) |
O1W | 0.0250 (5) | 0.0593 (7) | 0.0324 (6) | 0.0102 (5) | 0.0022 (5) | 0.0117 (5) |
O1—C9 | 1.2372 (15) | C12—C13 | 1.531 (2) |
O2—C17 | 1.2451 (16) | C13—C14 | 1.518 (2) |
O3—C17 | 1.2580 (16) | C1—H1 | 1.0000 |
O4—C15 | 1.2046 (16) | C2—H2B | 0.9900 |
O5—C15 | 1.3315 (17) | C2—H2A | 0.9900 |
O5—H5O | 0.890 (19) | C3—H3 | 1.0000 |
O1W—H2W | 0.81 (2) | C4—H4B | 0.9900 |
O1W—H1W | 0.90 (2) | C4—H4A | 0.9900 |
N1—C8 | 1.4857 (16) | C5—H5A | 0.9900 |
N1—C1 | 1.4705 (15) | C5—H5B | 0.9900 |
N1—C9 | 1.3322 (16) | C6—H6B | 0.9900 |
N2—C11 | 1.5054 (17) | C6—H6A | 0.9900 |
N2—C10 | 1.4982 (17) | C7—H7B | 0.9900 |
N2—H2NB | 0.884 (19) | C7—H7A | 0.9900 |
N2—H2NA | 0.959 (16) | C8—H8 | 1.0000 |
C1—C15 | 1.5137 (18) | C10—H10 | 1.0000 |
C1—C2 | 1.5362 (18) | C11—H11 | 1.0000 |
C2—C3 | 1.5339 (18) | C12—H12A | 0.9900 |
C3—C8 | 1.5385 (18) | C12—H12B | 0.9900 |
C3—C4 | 1.5287 (19) | C13—H13A | 0.9900 |
C4—C5 | 1.523 (2) | C13—H13B | 0.9900 |
C5—C6 | 1.529 (2) | C14—H14B | 0.9800 |
C6—C7 | 1.530 (2) | C14—H14C | 0.9800 |
C7—C8 | 1.5255 (18) | C14—H14A | 0.9800 |
C9—C10 | 1.5297 (16) | C16—H16C | 0.9800 |
C10—C16 | 1.5307 (19) | C16—H16A | 0.9800 |
C11—C12 | 1.5288 (19) | C16—H16B | 0.9800 |
C11—C17 | 1.5410 (18) | ||
C15—O5—H5O | 108.8 (13) | C4—C3—H3 | 108.00 |
H1W—O1W—H2W | 105 (2) | C3—C4—H4A | 109.00 |
C1—N1—C8 | 112.08 (9) | C3—C4—H4B | 109.00 |
C8—N1—C9 | 129.00 (10) | C5—C4—H4B | 109.00 |
C1—N1—C9 | 118.38 (10) | H4A—C4—H4B | 108.00 |
C10—N2—C11 | 115.24 (10) | C5—C4—H4A | 109.00 |
C10—N2—H2NB | 109.8 (10) | C4—C5—H5B | 109.00 |
C11—N2—H2NB | 110.5 (11) | C6—C5—H5A | 109.00 |
C11—N2—H2NA | 107.9 (10) | C6—C5—H5B | 109.00 |
C10—N2—H2NA | 109.2 (10) | H5A—C5—H5B | 108.00 |
H2NB—N2—H2NA | 103.6 (14) | C4—C5—H5A | 109.00 |
N1—C1—C15 | 112.46 (10) | C5—C6—H6B | 110.00 |
C2—C1—C15 | 109.99 (10) | C7—C6—H6A | 110.00 |
N1—C1—C2 | 104.01 (10) | C5—C6—H6A | 110.00 |
C1—C2—C3 | 103.41 (10) | H6A—C6—H6B | 108.00 |
C4—C3—C8 | 114.54 (11) | C7—C6—H6B | 110.00 |
C2—C3—C8 | 102.96 (10) | C6—C7—H7A | 110.00 |
C2—C3—C4 | 115.17 (11) | C6—C7—H7B | 110.00 |
C3—C4—C5 | 113.82 (11) | C8—C7—H7B | 110.00 |
C4—C5—C6 | 111.00 (12) | H7A—C7—H7B | 108.00 |
C5—C6—C7 | 109.46 (12) | C8—C7—H7A | 110.00 |
C6—C7—C8 | 110.44 (11) | C3—C8—H8 | 110.00 |
N1—C8—C3 | 101.30 (9) | C7—C8—H8 | 110.00 |
N1—C8—C7 | 111.98 (10) | N1—C8—H8 | 110.00 |
C3—C8—C7 | 113.55 (11) | C9—C10—H10 | 110.00 |
O1—C9—N1 | 122.63 (11) | C16—C10—H10 | 110.00 |
O1—C9—C10 | 119.87 (11) | N2—C10—H10 | 110.00 |
N1—C9—C10 | 117.41 (10) | C12—C11—H11 | 108.00 |
N2—C10—C16 | 109.22 (10) | C17—C11—H11 | 108.00 |
N2—C10—C9 | 108.13 (10) | N2—C11—H11 | 108.00 |
C9—C10—C16 | 110.03 (10) | C11—C12—H12B | 109.00 |
C12—C11—C17 | 109.63 (10) | C13—C12—H12A | 109.00 |
N2—C11—C12 | 110.07 (10) | C13—C12—H12B | 109.00 |
N2—C11—C17 | 112.00 (10) | H12A—C12—H12B | 108.00 |
C11—C12—C13 | 114.73 (12) | C11—C12—H12A | 109.00 |
C12—C13—C14 | 112.24 (13) | C12—C13—H13A | 109.00 |
O4—C15—O5 | 124.92 (12) | C12—C13—H13B | 109.00 |
O4—C15—C1 | 124.90 (12) | C14—C13—H13B | 109.00 |
O5—C15—C1 | 109.95 (11) | H13A—C13—H13B | 108.00 |
O2—C17—O3 | 126.28 (12) | C14—C13—H13A | 109.00 |
O2—C17—C11 | 117.45 (11) | C13—C14—H14A | 109.00 |
O3—C17—C11 | 116.23 (11) | C13—C14—H14B | 109.00 |
C2—C1—H1 | 110.00 | H14A—C14—H14B | 109.00 |
C15—C1—H1 | 110.00 | H14A—C14—H14C | 110.00 |
N1—C1—H1 | 110.00 | C13—C14—H14C | 109.00 |
C1—C2—H2B | 111.00 | H14B—C14—H14C | 109.00 |
C3—C2—H2A | 111.00 | C10—C16—H16B | 109.00 |
C1—C2—H2A | 111.00 | C10—C16—H16C | 109.00 |
H2A—C2—H2B | 109.00 | C10—C16—H16A | 109.00 |
C3—C2—H2B | 111.00 | H16A—C16—H16C | 109.00 |
C2—C3—H3 | 108.00 | H16B—C16—H16C | 109.00 |
C8—C3—H3 | 108.00 | H16A—C16—H16B | 110.00 |
C8—N1—C1—C2 | 1.77 (14) | C1—C2—C3—C4 | 164.73 (11) |
C9—N1—C1—C2 | 174.04 (11) | C4—C3—C8—N1 | −163.06 (11) |
C8—N1—C1—C15 | 120.74 (11) | C8—C3—C4—C5 | 42.24 (16) |
C9—N1—C1—C15 | −66.99 (15) | C2—C3—C8—N1 | −37.28 (12) |
C9—N1—C8—C7 | 89.79 (15) | C2—C3—C4—C5 | −76.90 (15) |
C1—N1—C9—O1 | −2.22 (18) | C4—C3—C8—C7 | −42.83 (15) |
C8—N1—C9—O1 | 168.55 (12) | C2—C3—C8—C7 | 82.95 (13) |
C1—N1—C9—C10 | 174.37 (11) | C3—C4—C5—C6 | −51.32 (16) |
C1—N1—C8—C3 | 22.37 (13) | C4—C5—C6—C7 | 60.79 (15) |
C9—N1—C8—C3 | −148.87 (13) | C5—C6—C7—C8 | −61.20 (15) |
C1—N1—C8—C7 | −98.97 (12) | C6—C7—C8—N1 | 166.25 (11) |
C8—N1—C9—C10 | −14.86 (19) | C6—C7—C8—C3 | 52.27 (15) |
C11—N2—C10—C9 | −59.50 (13) | O1—C9—C10—C16 | 74.70 (15) |
C10—N2—C11—C12 | −171.58 (10) | N1—C9—C10—N2 | 138.80 (11) |
C10—N2—C11—C17 | −49.34 (13) | N1—C9—C10—C16 | −101.99 (13) |
C11—N2—C10—C16 | −179.22 (10) | O1—C9—C10—N2 | −44.52 (15) |
C2—C1—C15—O4 | 88.09 (15) | N2—C11—C12—C13 | −60.04 (15) |
C2—C1—C15—O5 | −86.70 (13) | C17—C11—C12—C13 | 176.34 (11) |
C15—C1—C2—C3 | −146.10 (11) | N2—C11—C17—O2 | −29.99 (15) |
N1—C1—C15—O4 | −27.32 (18) | N2—C11—C17—O3 | 152.14 (11) |
N1—C1—C2—C3 | −25.46 (13) | C12—C11—C17—O2 | 92.49 (14) |
N1—C1—C15—O5 | 157.90 (11) | C12—C11—C17—O3 | −85.38 (13) |
C1—C2—C3—C8 | 39.36 (13) | C11—C12—C13—C14 | −170.69 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2NB···O2i | 0.884 (19) | 1.954 (17) | 2.7063 (15) | 142.1 (15) |
O1W—H1W···O3ii | 0.90 (2) | 1.89 (2) | 2.7725 (15) | 167 (2) |
N2—H2NA···O1W | 0.959 (16) | 1.850 (16) | 2.7923 (16) | 167.0 (15) |
O1W—H2W···O1 | 0.81 (2) | 2.29 (2) | 2.8307 (15) | 124 (2) |
O5—H5O···O3iii | 0.890 (19) | 1.73 (2) | 2.5929 (14) | 163.7 (19) |
C1—H1···O4iv | 1.00 | 2.45 | 3.2777 (16) | 140 |
C4—H4A···O1v | 0.99 | 2.56 | 3.3926 (17) | 142 |
C10—H10···O2 | 1.00 | 2.33 | 2.9600 (16) | 120 |
C11—H11···O5iv | 1.00 | 2.50 | 3.1808 (16) | 125 |
Symmetry codes: (i) x+1/2, −y+3/2, −z+2; (ii) x+1, y, z; (iii) −x+2, y+1/2, −z+3/2; (iv) −x+2, y−1/2, −z+3/2; (v) x−1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C17H28N2O5·H2O |
Mr | 358.43 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 100 |
a, b, c (Å) | 8.1645 (2), 10.0136 (2), 23.2429 (5) |
V (Å3) | 1900.25 (7) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.78 |
Crystal size (mm) | 0.30 × 0.25 × 0.20 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.799, 0.859 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19011, 3321, 3304 |
Rint | 0.026 |
(sin θ/λ)max (Å−1) | 0.593 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.027, 0.069, 1.08 |
No. of reflections | 3321 |
No. of parameters | 248 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.17, −0.15 |
Absolute structure | Flack (1983), with 1396 Friedel pairs |
Absolute structure parameter | 0.04 (14) |
Computer programs: APEX2 (Bruker, 2005), SAINT-Plus (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009) and Mercury (Macrae et al., 2008), PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2NB···O2i | 0.884 (19) | 1.954 (17) | 2.7063 (15) | 142.1 (15) |
O1W—H1W···O3ii | 0.90 (2) | 1.89 (2) | 2.7725 (15) | 167 (2) |
N2—H2NA···O1W | 0.959 (16) | 1.850 (16) | 2.7923 (16) | 167.0 (15) |
O1W—H2W···O1 | 0.81 (2) | 2.29 (2) | 2.8307 (15) | 124 (2) |
O5—H5O···O3iii | 0.890 (19) | 1.73 (2) | 2.5929 (14) | 163.7 (19) |
C1—H1···O4iv | 1.00 | 2.4500 | 3.2777 (16) | 140 |
C4—H4A···O1v | 0.99 | 2.5600 | 3.3926 (17) | 142 |
Symmetry codes: (i) x+1/2, −y+3/2, −z+2; (ii) x+1, y, z; (iii) −x+2, y+1/2, −z+3/2; (iv) −x+2, y−1/2, −z+3/2; (v) x−1, y, z. |
Perindopril is an angiotensin-converting-enzyme (ACE) inhibitor and has an established position in the main clinical treatment guidelines (Brugts et al., 2009). As an active pharmaceutical ingredient, perindopril is contained in numerous drugs, for example coversyl (L-arginine salt) and aceon (perindopril erbumine) (Telejko, 2007; Remko, 2009). There is an official standard for perindopril salts in the European Pharmacopoeia (European Directorate for the Quality of Medicines and HealthCare, 2011; Malenović et al., 2011). Perindopril is a non-sulfhydryl acid–ester prodrug, which after oral administration undergoes hydrolysis, promoted by the esterases in the liver and plasma, to active dicarboxylic acid perindoprilat (Laubie et al., 1984; Lecocq et al., 1990). It has wide-ranging pharmacodynamic properties which include, inter alia, vasodilation, restriction of cardiovascular remodelling, anti-atherogenic, anti-ischaemic and anti-thrombotic activity, enhanced endothelial function and improved fibrinolytic balance. With high tissue ACE affinity and a long duration of action, it has a positive safety and tolerability profile (Ferrari, 2005; Opie, 2011). Moreover, perindopril, and also ramipril, have been associated with lower mortality than other ACE inhibitors (Pilote et al., 2004). More than 20 years ago, Pascard et al. (1991) characterized a preferential solid-state conformation of perindoprilat ethanol disolvate [denoted (I).2EtOH] [Cambridge Structural Database (CSD; Allen, 2002) refcode SIWBUV], but in that structure, determined at room temperature, the ethanol molecules and the alkyl chain of perindoprilat were disordered (0.8:0.2), with some imprecisely refined and some missing H atoms. Thus, hydrogen-bonding interactions could not be reliably defined.
Very recently, we reported a more precise molecular structure of perindoprilat DMSO hemisolvate, (I).0.5DMSO (Bojarska et al., 2012). We have now investigated a new crystal form of perindoprilat, which crystallizes as a monohydrate, with one perindoprilat entity and one water molecule in the asymmetric unit, (I).H2O. From a pharmaceutical point of view a hydrate is considerably better. Thus, perindoprilat monohydrate, (I).H2O, is the subject of this article as a continuation of our studies.
A view of the molecular structure of (I).H2O is shown in Fig. 1. Like the two structures reported previously, (I).H2O crystallizes in an orthorhombic setting. The Sohnke space group P212121, which is the most common for solvates with a chiral main component (Cruz Cabeza et al., 2007), was unambiguously determined. The stereochemical configuration of the main molecule was established to be S at its five chiral centres (C atoms C1, C3, C8, C10 and C11) (Eliel & Wilen, 1994) and was confirmed by the Flack (1983) and Hooft (Hooft et al., 2008) parameters of 0.04 (14) and 0.05 (3), respectively, which is important for its pharmacological activity (Vincent & Schiavi, 1991).
Intramolecular proton transfer from atom O3 of the carboxy group to alanine atom N2 leads to the zwitterionic form of perindoprilat (see scheme and Fig. 1). The bond lengths C17—O3 and C17—O2 are equal, at 1.2580 (16) and 1.2451 (16) Å, respectively, indicating that electron delocalization has increased in this group. All the bond lengths and angles are in the usual ranges (Orpen et al., 1994).
The molecular structure of (I).H2O is largely comparable with the previously reported analogues. There is a fairly close resemblance between the perhydroindole group conformations, unlike the case of the n-alkyl chain, which is significantly different. The six-membered ring (C3–C8) adopts a slightly deformed chair conformation, as confirmed by the puckering parameters Q = 0.5445 (16) Å, θ = 165.17 (16)° and ϕ = 3.4 (6)° (Cremer & Pople, 1975; Spek, 2009). The proline ring (N1/C1–C3/C8) is in an envelope conformation [puckering parameters Q = 0.3973 (14) Å and ϕ = 284.50 (19)°]. The torsion angle between the alanine methyl group and the amide plane (O1/C9/C10/C16) is 74.70 (15)°. The terminal alkyl chain conformation of (I).H2O is synclinal [the N2—C11—C12—C13 dihedral [torsion?] angle is -60.04 (15)°]. The conformational difference between the perindoprilat molecules in all three known solvates involves only the orientation of the n-alkyl chain, which in (I).0.5DMSO and (I).2EtOH has a syn-clinal or anti-periplanar orientation. In Fig. 2, all the solvates are superimposed to emphasize the different n-alkyl chain orientations. It is worth mentioning that the geometric parameters of perindoprilat hydrate are in good agreement with those of two perindopril erbumine structures (Remko et al., 2011; CSD refcodes IVEGIA and IVEGOG).
In the crystal structure of (I).H2O, the perindoprilat molecules are connected to each other via intermolecular hydrogen bonding. Additional hydrogen bonds to the water molecules are also formed (Fig. 3, Table 1). Classical strong intermolecular interactions of O—H···O and N—H···O types create a three-dimensional network. The N—H···O hydrogen bonds are rather stronger and the O—H···O ones rather weaker in (I).H2O than in (I).0.5DMSO. Among the hydrogen bonds listed, O5—H5O···O3iii is the shortest [2.5929 (14) Å; symmetry code given in Table 1] and O1W—H2W···O1 is the longest [2.8307 (15) Å].
At the first level of graph-set theory (Etter et al., 1990) there are two chains perpendicular to each other: a five-membered chain with a C(5) graph-set motif which runs along the a axis, and a C(11) chain along the b axis, formed through N2—H2NB···O2(x + 1/2, -y + 3/2, -z + 2) and O5–H5O···O3(-x + 2, y + 1/2, -z + 3/2) interactions, respectively (Fig. 3). At the second level of graph-set theory (Bernstein et al., 1995), ten-membered helical and seven-membered extended chains are present, namely a C22(10) chain formed through O1W—H1W···O3(x + 1, y, z) and O1W—H2W···O1 interactions, and a C22(7) chain formed via N2—H2NA···O1W and O1W—H1W···O3(x + 1, y, z) interactions, forming a sheet along the a axis in which an R22 (7) motif can be identified (Fig. 3).
The water molecule acts as both a donor, donating its H atoms to the O atoms of the COO- and CO groups [O1W—H1W···O3(x + 1, y, z) and O1W–H2W···O1, respectively], and an acceptor [N2—H2NA···O1W], linking perindoprilat molecules. In the case of carbonyl group O1, atom H2W participates in O—H···O hydrogen bonds with quite an acute angle. N2—H2NB···O2(x + 1/2, -y + 3/2, -z + 2), O1W—H1W···O3(x + 1, y, z) and N2—H2NA···O1W interactions form other R44(13) edge-fused rings connecting three perindoprilat molecules and one water molecule together. In addition, at the third level of graph-set theory, a large ring motif with graph-set notation R56(29) formed through O1W—H2W···O1, O1W—H1W···O3(x + 1, y, z), O5—H5O···O3(-x + 2, y + 1/2, -z + 3/2) and N2—H2NA···O1W contacts can be identified.
There are also short weak C—H···O intermolecular contacts present. The contact C1—H1···O4iv, between the proline ring and the COOH group, has a length of 3.2777 (16) Å and an angle of 140° [symmetry code: (iv) -x + 2, y - 1/2, -z + 3/2], while the other hydrogen bond C4—H4A···O1v, between the six-membered ring and the carbonyl group, has a length of 3.3926 (17) Å and an angle of 142° [symmetry code: (v) x - 1, y, z]. All hydrogen-bonding interactions are listed in Table 1.
In conclusion, the crystal structure of (I).H2O has been resolved, revealing interesting conformational resemblances but also certain differences, especially different crystal packing motifs, compared with the (I).0.5DMSO and (I).2EtOH solvates published previously. The solvent water molecule appears to play a crucial role in the crystal packing and is a significant building element in the formation of a three-dimensional hydrogen-bond network.