(3S,4S)-3-Ethyl-4-hydr­oxy-3-(3-methoxy­phen­yl)-1-methyl­azepan-1-ium d-tartrate dihydrate

Wang, X.-H.; Chao, B.; Qiu, Z.-B.

doi:10.1107/S1600536808005898

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 64| Part 5| May 2008| Page o784

doi:10.1107/S1600536808005898

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(3S,4S)-3-Ethyl-4-hydroxy-3-(3-methoxyphenyl)-1-methylazepan-1-ium D-tartrate dihydrate

Xing-Hai Wang,^a Bo Chao ^a and Zhui-Bai Qiu ^a ^*

^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

(Received 25 February 2008; accepted 3 March 2008; online 2 April 2008)

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 absolute configuration was determined with reference to D-tartaric acid. The crystal structure 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

C₁₆H₂₆NO₂⁺·C₄H₅O₆⁻·2H₂O
M_r = 449.49
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.146 (3) Å
b = 10.812 (4) Å
c = 29.338 (11) Å
V = 2266.7 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 (2) K
0.20 × 0.15 × 0.12 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.979, T_max = 0.988
11334 measured reflections
2855 independent reflections
2173 reflections with I > 2σ(I)
R_int = 0.076

Refinement

R[F² > 2σ(F²)] = 0.061
wR(F²) = 0.163
S = 1.04
2855 reflections
319 parameters
19 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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⋯O7^iv	0.93	2.50	3.417 (6)	171
C7B—H7B1⋯O6^iv	0.97	2.51	3.176 (7)	126
C6B—H6B2⋯O1^v	0.97	2.39	3.056 (17)	125
Symmetry codes: (i) x-1, y, z; (ii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z]$ ; (iii) x+1, y, z; (iv) $[-x-1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (v) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ .

Data collection: SMART (Bruker, 2000 ); cell refinement: 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

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808005898/wn2243sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808005898/wn2243Isup2.hkl

checkCIF report

Comment top

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.

Related literature top

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 top

The title compound was prepared by standard procedures upon optical resolution of the racemate with D-tartaric acid. The synthesis of the racemic compound was described by Hao et al. (2005).

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: 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.

Figures top

	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.

(3S,4S)-3-Ethyl-4-hydroxy-3-(3-methoxyphenyl)-1-methylazepan-1-ium D-tartrate dihydrate top

Crystal data top

C₁₆H₂₆NO₂⁺·C₄H₅O₆⁻·2H₂O	F(000) = 968
M_r = 449.49	D_x = 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

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	2855 independent reflections
Radiation source: fine-focus sealed tube	2173 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.076
ϕ and ω scans	θ_max = 27.1°, θ_min = 1.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −9→4
T_min = 0.979, T_max = 0.988	k = −13→13
11334 measured reflections	l = −37→37

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)] = 0.061	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(F_o²) + (0.0771P)²] where P = (F_o² + 2F_c²)/3
2855 reflections	(Δ/σ)_max < 0.001
319 parameters	Δρ_max = 0.43 e Å⁻³
19 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₆H₂₆NO₂⁺·C₄H₅O₆⁻·2H₂O	V = 2266.7 (15) Å³
M_r = 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

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	2855 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	2173 reflections with I > 2σ(I)
T_min = 0.979, T_max = 0.988	R_int = 0.076
11334 measured reflections

Refinement top

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	Δρ_max = 0.43 e Å⁻³
2855 reflections	Δρ_min = −0.26 e Å⁻³
319 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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···O7^iv	0.93	2.50	3.417 (6)	171
C7B—H7B1···O6^iv	0.97	2.51	3.176 (7)	126
C6B—H6B2···O1^v	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
M_r	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)
T_min, T_max	0.979, 0.988
No. of measured, independent and observed [I > 2σ(I)] reflections	11334, 2855, 2173
R_int	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
Δρ_max, Δρ_min (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.

Hydrogen-bond geometry (Å, º) top

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···O7^iv	0.93	2.50	3.417 (6)	170.9
C7B—H7B1···O6^iv	0.97	2.51	3.176 (7)	125.6
C6B—H6B2···O1^v	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

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

(3S,4S)-3-Ethyl-4-hydr­­oxy-3-(3-meth­oxy­phen­yl)-1-methyl­azepan-1-ium D-tartrate dihydrate

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

(3S,4S)-3-Ethyl-4-hydroxy-3-(3-methoxyphenyl)-1-methylazepan-1-ium D-tartrate dihydrate