organic compounds
(3S,4S)-3-Ethyl-4-hydroxy-3-(3-methoxyphenyl)-1-methylazepan-1-ium D-tartrate dihydrate
aDepartment of Medicinal Chemistry, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China
*Correspondence e-mail: zbqiu@shmu.edu.cn
In the title compound, C16H26NO2+·C4H5O6−·2H2O, a meptazinol derivative, three C atoms of the azepane ring are disordered over two positions, with site-occupancy factors of 0.80 and 0.20; the major disorder component adopts a twist-chair conformation, while the minor component has a chair conformation. The benzene ring is axially substituted on the heterocyclic ring, resulting in a folded conformation of the cation. The was determined with reference to D-tartaric acid. The is stabilized by an extensive network of intra- and intermolecular O—H⋯O hydrogen bonds.
Related literature
For the synthesis of the racemate of the title compound, see: Hao et al. (2005). For conformational studies of seven-membered rings, see: Eliel et al. (1994); Entrena et al. (2005). For the analgesic activity and clinical use of meptazinol, see: Holmes (1985). For related literature, see: Bill et al. (1983).
Experimental
Crystal data
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Refinement
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Data collection: SMART (Bruker, 2000); cell SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXTL and local programs.
Supporting information
10.1107/S1600536808005898/wn2243sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808005898/wn2243Isup2.hkl
The title compound was prepared by standard procedures upon
of the racemate with D-tartaric acid. The synthesis of the was described by Hao et al. (2005).The H atoms bonded to N and O in the azepane ring, also the water hydrogen atoms were located in difference maps and refined with restraints: N—H = 0.89 (2) Å and O—H = 0.82 (2) and 0.83 (2) Å. The H atoms attached to O in the anion and all carbon-bound H atoms were placed in calculated positions and refined as riding; O—H = 0.82 and C—H = 0.93 - 0.98 Å; Uiso(H) = xUeq(parent atom) where x = 1.5 for O and 1.2 for C. In the cation, three C atoms with attached H atoms are disordered over two positions; the site occupancy factors are 0.80 and 0.20.
Data collection: SMART (Bruker, 2000); cell
SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and local programs.Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids at the 20% probability level. Hydrogen atoms are shown as spheres of arbitrary radius. Both azepane ring conformations are depicted; the minor chair conformation is drawn with open bonds. H atoms bonded to the C atoms of the azepane unit have been omitted for clarity. | |
Fig. 2. A view of the crystal packing, showing the hydrogen-bonding network (dashed lines). Only the twist-chair conformation of the azepane ring is shown. |
C16H26NO2+·C4H5O6−·2H2O | F(000) = 968 |
Mr = 449.49 | Dx = 1.317 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1000 reflections |
a = 7.146 (3) Å | θ = 2.8–22.5° |
b = 10.812 (4) Å | µ = 0.11 mm−1 |
c = 29.338 (11) Å | T = 293 K |
V = 2266.7 (15) Å3 | Prismatic, colorless |
Z = 4 | 0.20 × 0.15 × 0.12 mm |
Bruker SMART APEX CCD area-detector diffractometer | 2855 independent reflections |
Radiation source: fine-focus sealed tube | 2173 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.076 |
ϕ and ω scans | θmax = 27.1°, θmin = 1.4° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −9→4 |
Tmin = 0.979, Tmax = 0.988 | k = −13→13 |
11334 measured reflections | l = −37→37 |
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)] = 0.061 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.163 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0771P)2] where P = (Fo2 + 2Fc2)/3 |
2855 reflections | (Δ/σ)max < 0.001 |
319 parameters | Δρmax = 0.43 e Å−3 |
19 restraints | Δρmin = −0.26 e Å−3 |
C16H26NO2+·C4H5O6−·2H2O | V = 2266.7 (15) Å3 |
Mr = 449.49 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.146 (3) Å | µ = 0.11 mm−1 |
b = 10.812 (4) Å | T = 293 K |
c = 29.338 (11) Å | 0.20 × 0.15 × 0.12 mm |
Bruker SMART APEX CCD area-detector diffractometer | 2855 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 2173 reflections with I > 2σ(I) |
Tmin = 0.979, Tmax = 0.988 | Rint = 0.076 |
11334 measured reflections |
R[F2 > 2σ(F2)] = 0.061 | 19 restraints |
wR(F2) = 0.163 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.43 e Å−3 |
2855 reflections | Δρmin = −0.26 e Å−3 |
319 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
O1 | −1.0175 (7) | 0.3641 (4) | 0.46124 (12) | 0.0684 (12) | |
H1X | −1.114 (7) | 0.405 (6) | 0.457 (2) | 0.14 (4)* | |
O2 | −0.7001 (6) | 0.4436 (3) | 0.25255 (10) | 0.0628 (11) | |
O3 | −0.6276 (4) | 0.1543 (3) | 0.13391 (10) | 0.0425 (7) | |
H3 | −0.7400 | 0.1418 | 0.1307 | 0.064* | |
O4 | −0.6399 (5) | 0.2140 (4) | 0.06130 (12) | 0.0626 (10) | |
O5 | −0.2757 (4) | 0.2069 (3) | 0.05050 (10) | 0.0487 (8) | |
H5 | −0.3605 | 0.2365 | 0.0352 | 0.073* | |
O6 | −0.3086 (4) | 0.3996 (3) | 0.11490 (10) | 0.0430 (7) | |
H6 | −0.3766 | 0.4310 | 0.1342 | 0.065* | |
O7 | 0.0443 (4) | 0.3653 (3) | 0.13158 (11) | 0.0480 (8) | |
O8 | 0.0205 (4) | 0.1619 (3) | 0.13574 (10) | 0.0391 (7) | |
O9 | −0.6223 (5) | 0.4527 (3) | 0.15827 (12) | 0.0473 (8) | |
H9X | −0.651 (9) | 0.457 (5) | 0.1855 (9) | 0.066 (17)* | |
H9Y | −0.721 (6) | 0.424 (7) | 0.147 (2) | 0.11 (3)* | |
O10 | 0.0604 (5) | 0.1148 (3) | 0.01603 (11) | 0.0472 (8) | |
H10X | −0.033 (5) | 0.142 (5) | 0.0284 (18) | 0.067 (18)* | |
H10Y | 0.121 (8) | 0.135 (6) | 0.0387 (14) | 0.08 (2)* | |
N1 | −0.9584 (7) | 0.0649 (3) | 0.42832 (11) | 0.0451 (10) | |
H1 | −0.925 (6) | 0.018 (3) | 0.4048 (10) | 0.029 (11)* | |
C2 | −1.0991 (6) | 0.1554 (4) | 0.41055 (14) | 0.0381 (9) | |
H2A | −1.1746 | 0.1816 | 0.4363 | 0.046* | |
H2B | −1.1814 | 0.1103 | 0.3902 | 0.046* | |
C3 | −1.0364 (6) | 0.2740 (4) | 0.38507 (13) | 0.0340 (9) | |
C4 | −0.9242 (8) | 0.3610 (4) | 0.41797 (14) | 0.0480 (12) | |
H4 | −0.9289 | 0.4447 | 0.4052 | 0.058* | |
C5A | −0.7183 (8) | 0.3276 (5) | 0.42468 (16) | 0.0575 (13) | 0.80 |
H5A | −0.6738 | 0.3677 | 0.4522 | 0.069* | 0.80 |
H5B | −0.6473 | 0.3609 | 0.3993 | 0.069* | 0.80 |
C6A | −0.6754 (8) | 0.1822 (6) | 0.42849 (18) | 0.0489 (15) | 0.80 |
H6A | −0.6734 | 0.1480 | 0.3979 | 0.059* | 0.80 |
H6B | −0.5509 | 0.1721 | 0.4412 | 0.059* | 0.80 |
C7A | −0.8041 (9) | 0.1098 (5) | 0.4556 (2) | 0.0691 (15) | 0.80 |
H7A | −0.8522 | 0.1602 | 0.4803 | 0.083* | 0.80 |
H7B | −0.7382 | 0.0401 | 0.4689 | 0.083* | 0.80 |
C5B | −0.7183 (8) | 0.3276 (5) | 0.42468 (16) | 0.0575 (13) | 0.20 |
H5B1 | −0.6630 | 0.2960 | 0.3968 | 0.069* | 0.20 |
H5B2 | −0.6463 | 0.3980 | 0.4353 | 0.069* | 0.20 |
C6B | −0.730 (4) | 0.2392 (14) | 0.4568 (5) | 0.049 (6) | 0.20 |
H6B1 | −0.7994 | 0.2782 | 0.4814 | 0.058* | 0.20 |
H6B2 | −0.6033 | 0.2304 | 0.4680 | 0.058* | 0.20 |
C7B | −0.8041 (9) | 0.1098 (5) | 0.4556 (2) | 0.0691 (15) | 0.20 |
H7B1 | −0.6980 | 0.0580 | 0.4477 | 0.083* | 0.20 |
H7B2 | −0.8358 | 0.0895 | 0.4869 | 0.083* | 0.20 |
C8 | −1.0659 (12) | −0.0250 (5) | 0.45936 (18) | 0.082 (2) | |
H8A | −0.9931 | −0.0986 | 0.4638 | 0.123* | |
H8B | −1.1831 | −0.0462 | 0.4454 | 0.123* | |
H8C | −1.0888 | 0.0136 | 0.4883 | 0.123* | |
C9 | −1.2199 (7) | 0.3436 (5) | 0.37375 (18) | 0.0567 (13) | |
H9A | −1.2956 | 0.3471 | 0.4012 | 0.068* | |
H9B | −1.1882 | 0.4280 | 0.3656 | 0.068* | |
C10 | −1.3354 (9) | 0.2906 (7) | 0.3367 (2) | 0.0770 (18) | |
H10A | −1.2604 | 0.2814 | 0.3097 | 0.116* | |
H10B | −1.4386 | 0.3448 | 0.3303 | 0.116* | |
H10C | −1.3821 | 0.2112 | 0.3459 | 0.116* | |
C11 | −0.9309 (6) | 0.2535 (4) | 0.34049 (13) | 0.0338 (9) | |
C12 | −0.8603 (6) | 0.3570 (4) | 0.31824 (13) | 0.0388 (10) | |
H12 | −0.8704 | 0.4346 | 0.3317 | 0.047* | |
C13 | −0.7751 (7) | 0.3450 (5) | 0.27617 (14) | 0.0442 (10) | |
C14 | −0.7607 (8) | 0.2313 (5) | 0.25529 (15) | 0.0528 (13) | |
H14 | −0.7037 | 0.2241 | 0.2269 | 0.063* | |
C15 | −0.8316 (8) | 0.1289 (5) | 0.27677 (14) | 0.0523 (13) | |
H15 | −0.8234 | 0.0519 | 0.2628 | 0.063* | |
C16 | −0.9167 (6) | 0.1400 (4) | 0.31989 (13) | 0.0412 (10) | |
H16 | −0.9634 | 0.0701 | 0.3344 | 0.049* | |
C17 | −0.6939 (10) | 0.5617 (5) | 0.27368 (17) | 0.0643 (15) | |
H17A | −0.8170 | 0.5840 | 0.2839 | 0.096* | |
H17B | −0.6501 | 0.6220 | 0.2521 | 0.096* | |
H17C | −0.6104 | 0.5590 | 0.2993 | 0.096* | |
C18 | −0.5553 (6) | 0.1854 (4) | 0.09532 (14) | 0.0357 (9) | |
C19 | −0.3405 (5) | 0.1845 (4) | 0.09492 (14) | 0.0348 (9) | |
H19 | −0.2979 | 0.1022 | 0.1042 | 0.042* | |
C20 | −0.2607 (5) | 0.2792 (4) | 0.12837 (13) | 0.0311 (8) | |
H20 | −0.3144 | 0.2636 | 0.1586 | 0.037* | |
C21 | −0.0461 (6) | 0.2685 (3) | 0.13173 (12) | 0.0304 (8) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.102 (3) | 0.054 (2) | 0.0493 (19) | −0.015 (2) | 0.036 (2) | −0.0117 (16) |
O2 | 0.093 (3) | 0.062 (2) | 0.0337 (16) | −0.020 (2) | 0.0192 (19) | −0.0047 (14) |
O3 | 0.0267 (13) | 0.0508 (18) | 0.0499 (17) | −0.0006 (14) | −0.0032 (13) | 0.0072 (15) |
O4 | 0.0358 (17) | 0.102 (3) | 0.0504 (19) | −0.001 (2) | −0.0073 (16) | 0.0149 (19) |
O5 | 0.0355 (16) | 0.071 (2) | 0.0396 (16) | 0.0106 (16) | 0.0018 (14) | −0.0067 (15) |
O6 | 0.0343 (16) | 0.0337 (15) | 0.0612 (19) | 0.0056 (13) | 0.0115 (15) | 0.0052 (13) |
O7 | 0.0328 (15) | 0.0357 (16) | 0.076 (2) | −0.0038 (14) | −0.0019 (17) | 0.0016 (15) |
O8 | 0.0268 (14) | 0.0354 (15) | 0.0550 (17) | 0.0019 (12) | −0.0009 (13) | 0.0041 (13) |
O9 | 0.0393 (18) | 0.059 (2) | 0.0433 (19) | −0.0009 (16) | 0.0073 (16) | −0.0042 (16) |
O10 | 0.0456 (19) | 0.0567 (19) | 0.0392 (17) | 0.0046 (18) | 0.0032 (17) | −0.0048 (15) |
N1 | 0.070 (3) | 0.0334 (18) | 0.0320 (18) | 0.006 (2) | −0.007 (2) | −0.0040 (14) |
C2 | 0.042 (2) | 0.032 (2) | 0.040 (2) | −0.0049 (19) | 0.0031 (19) | 0.0004 (17) |
C3 | 0.034 (2) | 0.0302 (19) | 0.038 (2) | 0.0035 (18) | 0.0068 (19) | 0.0033 (16) |
C4 | 0.077 (3) | 0.033 (2) | 0.034 (2) | −0.005 (2) | 0.024 (2) | −0.0071 (17) |
C5A | 0.055 (3) | 0.078 (4) | 0.039 (2) | −0.020 (3) | −0.007 (2) | −0.008 (2) |
C6A | 0.039 (3) | 0.079 (4) | 0.029 (3) | 0.018 (3) | −0.008 (2) | 0.004 (3) |
C7A | 0.074 (4) | 0.061 (3) | 0.073 (3) | 0.007 (3) | −0.020 (3) | −0.002 (3) |
C5B | 0.055 (3) | 0.078 (4) | 0.039 (2) | −0.020 (3) | −0.007 (2) | −0.008 (2) |
C6B | 0.086 (18) | 0.046 (9) | 0.014 (8) | 0.022 (10) | −0.020 (11) | −0.001 (8) |
C7B | 0.074 (4) | 0.061 (3) | 0.073 (3) | 0.007 (3) | −0.020 (3) | −0.002 (3) |
C8 | 0.147 (7) | 0.049 (3) | 0.050 (3) | 0.009 (4) | 0.039 (4) | 0.014 (2) |
C9 | 0.048 (3) | 0.061 (3) | 0.062 (3) | 0.016 (3) | 0.009 (3) | 0.011 (2) |
C10 | 0.050 (3) | 0.104 (5) | 0.077 (4) | 0.020 (4) | −0.010 (3) | 0.003 (4) |
C11 | 0.030 (2) | 0.042 (2) | 0.0300 (18) | 0.0037 (18) | −0.0032 (17) | 0.0003 (16) |
C12 | 0.046 (2) | 0.043 (2) | 0.0281 (19) | −0.003 (2) | −0.0044 (18) | −0.0038 (17) |
C13 | 0.043 (2) | 0.056 (3) | 0.033 (2) | −0.005 (2) | −0.0041 (19) | 0.0015 (19) |
C14 | 0.059 (3) | 0.068 (3) | 0.032 (2) | 0.000 (3) | 0.006 (2) | −0.009 (2) |
C15 | 0.068 (3) | 0.051 (3) | 0.038 (2) | 0.000 (3) | 0.002 (2) | −0.011 (2) |
C16 | 0.048 (3) | 0.039 (2) | 0.036 (2) | 0.006 (2) | 0.0024 (19) | 0.0006 (17) |
C17 | 0.083 (4) | 0.060 (3) | 0.050 (3) | −0.017 (3) | 0.003 (3) | 0.004 (2) |
C18 | 0.0300 (19) | 0.037 (2) | 0.040 (2) | 0.0026 (18) | −0.004 (2) | −0.0023 (17) |
C19 | 0.028 (2) | 0.036 (2) | 0.040 (2) | 0.0058 (17) | −0.0012 (18) | 0.0007 (17) |
C20 | 0.0279 (19) | 0.0302 (19) | 0.0351 (19) | 0.0021 (16) | 0.0045 (17) | 0.0018 (16) |
C21 | 0.0273 (18) | 0.033 (2) | 0.0313 (18) | −0.0011 (17) | 0.0036 (17) | 0.0027 (15) |
O1—C4 | 1.434 (5) | C6A—H6A | 0.9700 |
O1—H1X | 0.83 (2) | C6A—H6B | 0.9700 |
O2—C13 | 1.380 (6) | C7A—H7A | 0.9700 |
O2—C17 | 1.420 (6) | C7A—H7B | 0.9700 |
O3—C18 | 1.289 (5) | C6B—H6B1 | 0.9700 |
O3—H3 | 0.8200 | C6B—H6B2 | 0.9700 |
O4—C18 | 1.207 (5) | C8—H8A | 0.9599 |
O5—C19 | 1.404 (5) | C8—H8B | 0.9599 |
O5—H5 | 0.8200 | C8—H8C | 0.9599 |
O6—C20 | 1.403 (5) | C9—C10 | 1.482 (8) |
O6—H6 | 0.8200 | C9—H9A | 0.9700 |
O7—C21 | 1.230 (5) | C9—H9B | 0.9700 |
O8—C21 | 1.252 (5) | C10—H10A | 0.9599 |
O9—H9X | 0.83 (2) | C10—H10B | 0.9599 |
O9—H9Y | 0.83 (2) | C10—H10C | 0.9599 |
O10—H10X | 0.82 (2) | C11—C16 | 1.371 (6) |
O10—H10Y | 0.82 (2) | C11—C12 | 1.391 (6) |
N1—C7A | 1.447 (7) | C12—C13 | 1.383 (6) |
N1—C2 | 1.496 (6) | C12—H12 | 0.9300 |
N1—C8 | 1.538 (7) | C13—C14 | 1.377 (7) |
N1—H1 | 0.890 (19) | C14—C15 | 1.371 (7) |
C2—C3 | 1.551 (5) | C14—H14 | 0.9300 |
C2—H2A | 0.9700 | C15—C16 | 1.409 (6) |
C2—H2B | 0.9700 | C15—H15 | 0.9300 |
C3—C11 | 1.526 (5) | C16—H16 | 0.9300 |
C3—C9 | 1.548 (7) | C17—H17A | 0.9599 |
C3—C4 | 1.568 (6) | C17—H17B | 0.9599 |
C4—C5A | 1.528 (8) | C17—H17C | 0.9599 |
C4—H4 | 0.9800 | C18—C19 | 1.536 (6) |
C5A—C6A | 1.606 (8) | C19—C20 | 1.528 (6) |
C5A—H5A | 0.9700 | C19—H19 | 0.9800 |
C5A—H5B | 0.9700 | C20—C21 | 1.541 (6) |
C6A—C7A | 1.446 (8) | C20—H20 | 0.9800 |
C4—O1—H1X | 106 (6) | H8B—C8—H8C | 109.5 |
C13—O2—C17 | 119.2 (4) | C10—C9—C3 | 116.2 (5) |
C18—O3—H3 | 109.5 | C10—C9—H9A | 108.2 |
C19—O5—H5 | 109.5 | C3—C9—H9A | 108.2 |
C20—O6—H6 | 109.5 | C10—C9—H9B | 108.2 |
H9X—O9—H9Y | 101 (6) | C3—C9—H9B | 108.2 |
H10X—O10—H10Y | 89 (5) | H9A—C9—H9B | 107.4 |
C7A—N1—C2 | 119.1 (4) | C9—C10—H10A | 109.5 |
C7A—N1—C8 | 105.4 (4) | C9—C10—H10B | 109.5 |
C2—N1—C8 | 106.5 (4) | H10A—C10—H10B | 109.5 |
C7A—N1—H1 | 115 (3) | C9—C10—H10C | 109.5 |
C2—N1—H1 | 107 (3) | H10A—C10—H10C | 109.5 |
C8—N1—H1 | 103 (3) | H10B—C10—H10C | 109.5 |
N1—C2—C3 | 121.0 (4) | C16—C11—C12 | 119.1 (4) |
N1—C2—H2A | 107.1 | C16—C11—C3 | 123.0 (4) |
C3—C2—H2A | 107.1 | C12—C11—C3 | 117.7 (3) |
N1—C2—H2B | 107.1 | C13—C12—C11 | 120.2 (4) |
C3—C2—H2B | 107.1 | C13—C12—H12 | 119.9 |
H2A—C2—H2B | 106.8 | C11—C12—H12 | 119.9 |
C11—C3—C9 | 107.8 (3) | C14—C13—O2 | 115.9 (4) |
C11—C3—C2 | 115.8 (3) | C14—C13—C12 | 121.0 (4) |
C9—C3—C2 | 105.1 (4) | O2—C13—C12 | 123.1 (4) |
C11—C3—C4 | 111.2 (3) | C15—C14—C13 | 119.3 (4) |
C9—C3—C4 | 105.9 (4) | C15—C14—H14 | 120.4 |
C2—C3—C4 | 110.3 (3) | C13—C14—H14 | 120.4 |
O1—C4—C5A | 109.8 (4) | C14—C15—C16 | 120.2 (4) |
O1—C4—C3 | 108.7 (4) | C14—C15—H15 | 119.9 |
C5A—C4—C3 | 115.5 (4) | C16—C15—H15 | 119.9 |
O1—C4—H4 | 107.5 | C11—C16—C15 | 120.3 (4) |
C5A—C4—H4 | 107.5 | C11—C16—H16 | 119.9 |
C3—C4—H4 | 107.5 | C15—C16—H16 | 119.9 |
C4—C5A—C6A | 115.1 (4) | O2—C17—H17A | 109.5 |
C4—C5A—H5A | 108.5 | O2—C17—H17B | 109.5 |
C6A—C5A—H5A | 108.5 | H17A—C17—H17B | 109.5 |
C4—C5A—H5B | 108.5 | O2—C17—H17C | 109.5 |
C6A—C5A—H5B | 108.5 | H17A—C17—H17C | 109.5 |
H5A—C5A—H5B | 107.5 | H17B—C17—H17C | 109.5 |
C7A—C6A—C5A | 116.5 (5) | O4—C18—O3 | 126.3 (4) |
C7A—C6A—H6A | 108.2 | O4—C18—C19 | 119.7 (4) |
C5A—C6A—H6A | 108.2 | O3—C18—C19 | 114.0 (4) |
C7A—C6A—H6B | 108.2 | O5—C19—C20 | 111.0 (3) |
C5A—C6A—H6B | 108.2 | O5—C19—C18 | 109.6 (3) |
H6A—C6A—H6B | 107.3 | C20—C19—C18 | 111.4 (3) |
C6A—C7A—N1 | 111.2 (5) | O5—C19—H19 | 108.3 |
C6A—C7A—H7A | 109.4 | C20—C19—H19 | 108.3 |
N1—C7A—H7A | 109.4 | C18—C19—H19 | 108.3 |
C6A—C7A—H7B | 109.4 | O6—C20—C19 | 110.5 (3) |
N1—C7A—H7B | 109.4 | O6—C20—C21 | 109.3 (3) |
H7A—C7A—H7B | 108.0 | C19—C20—C21 | 111.2 (3) |
H6B1—C6B—H6B2 | 105.5 | O6—C20—H20 | 108.6 |
N1—C8—H8A | 109.5 | C19—C20—H20 | 108.6 |
N1—C8—H8B | 109.5 | C21—C20—H20 | 108.6 |
H8A—C8—H8B | 109.5 | O7—C21—O8 | 125.7 (4) |
N1—C8—H8C | 109.5 | O7—C21—C20 | 117.3 (4) |
H8A—C8—H8C | 109.5 | O8—C21—C20 | 117.0 (3) |
C7A—N1—C2—C3 | 50.1 (6) | C4—C3—C11—C12 | −48.4 (5) |
C8—N1—C2—C3 | 168.8 (4) | C16—C11—C12—C13 | −0.8 (6) |
N1—C2—C3—C11 | 62.8 (5) | C3—C11—C12—C13 | −175.4 (4) |
N1—C2—C3—C9 | −178.4 (4) | C17—O2—C13—C14 | −174.2 (5) |
N1—C2—C3—C4 | −64.6 (5) | C17—O2—C13—C12 | 5.9 (8) |
C11—C3—C4—O1 | −172.6 (4) | C11—C12—C13—C14 | 0.9 (7) |
C9—C3—C4—O1 | 70.6 (5) | C11—C12—C13—O2 | −179.2 (4) |
C2—C3—C4—O1 | −42.7 (5) | O2—C13—C14—C15 | 179.8 (5) |
C11—C3—C4—C5A | −48.7 (5) | C12—C13—C14—C15 | −0.3 (7) |
C9—C3—C4—C5A | −165.5 (4) | C13—C14—C15—C16 | −0.5 (8) |
C2—C3—C4—C5A | 81.2 (4) | C12—C11—C16—C15 | 0.0 (7) |
O1—C4—C5A—C6A | 83.7 (5) | C3—C11—C16—C15 | 174.4 (4) |
C3—C4—C5A—C6A | −39.7 (5) | C14—C15—C16—C11 | 0.6 (7) |
C4—C5A—C6A—C7A | −41.9 (6) | O4—C18—C19—O5 | −6.3 (6) |
C5A—C6A—C7A—N1 | 88.8 (6) | O3—C18—C19—O5 | 174.0 (3) |
C2—N1—C7A—C6A | −68.9 (6) | O4—C18—C19—C20 | 116.9 (5) |
C8—N1—C7A—C6A | 171.8 (5) | O3—C18—C19—C20 | −62.9 (5) |
C11—C3—C9—C10 | 50.3 (6) | O5—C19—C20—O6 | 57.8 (4) |
C2—C3—C9—C10 | −73.7 (5) | C18—C19—C20—O6 | −64.6 (4) |
C4—C3—C9—C10 | 169.4 (5) | O5—C19—C20—C21 | −63.7 (4) |
C9—C3—C11—C16 | −107.3 (5) | C18—C19—C20—C21 | 173.9 (3) |
C2—C3—C11—C16 | 10.1 (6) | O6—C20—C21—O7 | 13.9 (5) |
C4—C3—C11—C16 | 137.1 (4) | C19—C20—C21—O7 | 136.2 (4) |
C9—C3—C11—C12 | 67.2 (5) | O6—C20—C21—O8 | −168.1 (3) |
C2—C3—C11—C12 | −175.4 (4) | C19—C20—C21—O8 | −45.9 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
O5—H5···O4 | 0.82 | 2.15 | 2.623 (5) | 116 |
O6—H6···O9 | 0.82 | 1.91 | 2.641 (5) | 149 |
O9—H9X···O2 | 0.83 (2) | 2.00 (2) | 2.823 (5) | 171 (6) |
O10—H10X···O5 | 0.82 (2) | 1.98 (2) | 2.790 (5) | 173 (6) |
C7A—H7A···O1 | 0.97 | 2.56 | 3.149 (8) | 119 |
C6B—H6B1···O1 | 0.97 | 1.91 | 2.46 (3) | 113 |
O9—H9Y···O7i | 0.83 (2) | 1.85 (2) | 2.680 (5) | 171 (7) |
O3—H3···O8i | 0.82 | 1.73 | 2.516 (4) | 160 |
O5—H5···O10ii | 0.82 | 2.27 | 2.983 (5) | 145 |
O10—H10Y···O4iii | 0.82 (2) | 2.02 (4) | 2.739 (5) | 145 (6) |
C16—H16···O7iv | 0.93 | 2.50 | 3.417 (6) | 171 |
C7B—H7B1···O6iv | 0.97 | 2.51 | 3.176 (7) | 126 |
C6B—H6B2···O1v | 0.97 | 2.39 | 3.056 (17) | 125 |
Symmetry codes: (i) x−1, y, z; (ii) x−1/2, −y+1/2, −z; (iii) x+1, y, z; (iv) −x−1, y−1/2, −z+1/2; (v) x+1/2, −y+1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C16H26NO2+·C4H5O6−·2H2O |
Mr | 449.49 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 7.146 (3), 10.812 (4), 29.338 (11) |
V (Å3) | 2266.7 (15) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.20 × 0.15 × 0.12 |
Data collection | |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.979, 0.988 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 11334, 2855, 2173 |
Rint | 0.076 |
(sin θ/λ)max (Å−1) | 0.642 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.061, 0.163, 1.04 |
No. of reflections | 2855 |
No. of parameters | 319 |
No. of restraints | 19 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.43, −0.26 |
Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SHELXTL (Sheldrick, 2008) and ORTEP-3 (Farrugia, 1997), SHELXTL (Sheldrick, 2008) and local programs.
D—H···A | D—H | H···A | D···A | D—H···A |
O5—H5···O4 | 0.82 | 2.15 | 2.623 (5) | 116.4 |
O6—H6···O9 | 0.82 | 1.91 | 2.641 (5) | 148.5 |
O9—H9X···O2 | 0.83 (2) | 2.00 (2) | 2.823 (5) | 171 (6) |
O10—H10X···O5 | 0.82 (2) | 1.98 (2) | 2.790 (5) | 173 (6) |
C7A—H7A···O1 | 0.97 | 2.56 | 3.149 (8) | 118.9 |
C6B—H6B1···O1 | 0.97 | 1.91 | 2.46 (3) | 113.3 |
O9—H9Y···O7i | 0.83 (2) | 1.85 (2) | 2.680 (5) | 171 (7) |
O3—H3···O8i | 0.82 | 1.73 | 2.516 (4) | 159.6 |
O5—H5···O10ii | 0.82 | 2.27 | 2.983 (5) | 145.4 |
O10—H10Y···O4iii | 0.82 (2) | 2.02 (4) | 2.739 (5) | 145 (6) |
C16—H16···O7iv | 0.93 | 2.50 | 3.417 (6) | 170.9 |
C7B—H7B1···O6iv | 0.97 | 2.51 | 3.176 (7) | 125.6 |
C6B—H6B2···O1v | 0.97 | 2.39 | 3.056 (17) | 125.0 |
Symmetry codes: (i) x−1, y, z; (ii) x−1/2, −y+1/2, −z; (iii) x+1, y, z; (iv) −x−1, y−1/2, −z+1/2; (v) x+1/2, −y+1/2, −z+1. |
Acknowledgements
This work is funded in part by the National Natural Science Foundation of China (grant No. 30472088).
References
Bill, D. J., Hartley, J. E., Stephens, R. J. & Thompson, A. M. (1983). Br. J. Pharm. 79, 191–199. CrossRef CAS Google Scholar
Bruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Eliel, E. L., Wilen, S. H. & Mander, L. N. (1994). Stereochemistry of Organic Compounds, pp. 762–769. New York: Wiley. Google Scholar
Entrena, A., Campos, J. M., Gallo, M. A. E. & Spinosa, A. (2005). Arkivoc, 6, 88-108. CrossRef Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Hao, J. L., Li, W., Xie, Q., Chen, Y. & Qiu, Z. B. (2005). J. Fudan Univ. (Med. Sci.), 32, 173–177. CAS Google Scholar
Holmes, B. (1985). Drugs, 30, 285–312. CrossRef CAS PubMed Web of Science Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Meptazinol is a selective µ agonist with additional central anticholinergic activity, which has been used for treating pain associated with labour and kidney problems (Holmes, 1985). Many studies have shown meptazinol to have an advantage over other opioid analgesics because of its lack of adverse cardiorespiratory effects and low addiction liability (Bill et al., 1983); this makes it an ideal precursor for further investigation. During the course of our structural optimization of meptazinol, the title compound was synthesized by introducing an OH group at the 4-position, followed by resolution with D-tartaric acid.
The absolute configuration of the azepane ring atoms is N1(R), C3(S) and C4(S), according to the reference molecule D-tartaric acid. The O—H functionalities, carboxyl group and H2O are known to be efficient donor and acceptor groups for hydrogen bonding, and they form an extensive hydrogen-bond network, which stabilizes the structure. The 3-methoxyphenyl substituent at C3 is trans to the OH group at C4 and cis to the N—H bond, resulting in a folded conformation of the cation.
The major disorder component adopts a twist-chair conformation, while the minor component has a chair conformation. The twist-chair conformation of seven-membered rings is known to be more stable than the chair conformation (Entrena et al., 2005). Thus, the relative proportion of both conformers observed within the crystal structure may reflect the statistical partitioning of the two populations of azepane structures corresponding to different energetic states.