(S)-1-(2-Chloro­phen­yl)-2-oxocyclo­hexan-1-aminium d-tartrate

Hojahmat, M.; Zheng, G.; Siegler, M.; Parkin, S.; Biermann, M.; Crooks, P.A.

doi:10.1107/S1600536811006131

organic compounds

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ISSN: 2056-9890

Volume 67| Part 3| March 2011| Page o736

doi:10.1107/S1600536811006131

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(S)-1-(2-Chlorophenyl)-2-oxocyclohexan-1-aminium D-tartrate

Marhaba Hojahmat,^a Guangrong Zheng,^b Max Siegler,^c Sean Parkin,^c Manfred Biermann ^d and Peter A. Crooks ^b ^*

^aYaupon Therapeutics, Inc., 259 North Radnor-Chester Road, Suite 205, Radnor, PA 19087, USA, ^bDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA, ^cDepartment of Chemistry, University of Kentucky, Lexington, KY 40536, USA, and ^dResodyn Corporation, 130 North Main Street, Suite 600, Butte, MT 59701, USA
^*Correspondence e-mail: pcrooks@email.uky.edu

(Received 6 December 2010; accepted 17 February 2011; online 26 February 2011)

In the title compound, C₁₂H₁₅ClNO⁺·C₄H₅O₆⁻, the cyclohexanone ring adopts a chair conformation. The benzene ring is significantly twisted so that it is in an almost perpendicular position to the C—N bond with a C_Ar—C_Ar—C—N torsion angle of −96.5 (5)°. Intermolecular N—H⋯O and O—H⋯O hydrogen bonds are observed in the crystal structure.

Related literature

For background to ketamine, see: Holtman (2006 ); Holtman et al. (2006 ); Heshmati et al. (2003 ); Kohrs & Durieux (1998 ). For the synthesis, see: Hong & Davisson (1982 ); Parcell & Sanchez (1981 ).

Experimental

Crystal data

C₁₂H₁₅ClNO⁺·C₄H₅O₆⁻
M_r = 373.78
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.1411 (2) Å
b = 9.9878 (4) Å
c = 23.7530 (11) Å
V = 1694.16 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 90 K
0.20 × 0.20 × 0.03 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.949, T_max = 0.992
13735 measured reflections
2986 independent reflections
1519 reflections with I > 2σ(I)
R_int = 0.110

Refinement

R[F² > 2σ(F²)] = 0.060
wR(F²) = 0.139
S = 0.96
2986 reflections
230 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.27 e Å⁻³
Absolute structure: Flack (1983 ), 1241 Friedel pairs
Flack parameter: 0.10 (10)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O7ⁱ	0.91	1.81	2.715 (5)	176
N1—H1B⋯O4	0.91	2.05	2.856 (5)	147
N1—H1C⋯O3ⁱⁱ	0.91	2.29	2.893 (5)	123
N1—H1C⋯O5ⁱⁱ	0.91	2.37	3.001 (5)	126
O2—H2A⋯O1ⁱⁱⁱ	0.84	2.60	3.388 (5)	157
O5—H5A⋯O6^iv	0.84	2.09	2.864 (5)	153
O6—H6⋯O4^v	0.84	1.64	2.460 (5)	166
O6—H6⋯O3^v	0.84	2.62	3.265 (5)	134
Symmetry codes: (i) $[-x+2, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iii) $[-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iv) $[-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (v) x+1, y, z.

Data collection: COLLECT (Nonius, 1998 ); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 and local procedures.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811006131/hg2766sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811006131/hg2766Isup2.hkl

checkCIF report

Comment top

Ketalar^TM, the racemic mixture of R- and S-Ketamines is becoming the sedative and anesthetic of choice for emergency sedation in children and victims with unknown medical history, e.g. from traffic accidents to battlefield conditions, because it causes minimal respiratory depression in comparison to other anesthetics (Heshmati et al., 2003). S-Ketamine was found 3–4 times more potent as an anesthetic than its R-enantiomer, and twice as potent as Ketalar^TM with fewer side effects such as psychedelic, disorientation and anxiety (Kohrs & Durieux, 1998). S-Norketamine, the major metabolite of S-Ketamine in humans and animals, is emerging as a novel drug for treatment of neuropathic pain (Holtman et al., 2006) and for analgesia (Holtman, 2006). To confirm the absolute configuration of (+)-norketamine, herein we report on the X-ray crystallographic characterization of crystalline S-norketamine D-tartrate salt.

Related literature top

For background to ketamine, see: Holtman (2006); Holtman et al. (2006); Heshmati et al. (2003); Kohrs & Durieux (1998). For the synthesis, see: Hong & Davisson (1982); Parcell & Sanchez (1981).

Experimental top

S-Norketamine was obtained as a D-tartrate salt form via chiral resolution of racemic norketamine by fractional crystallization of the D-tartrate salt (Hong & Davisson, 1982). Racemic norketamine was produced in large quantity according to literature report (Parcell & Sanchez, 1981). The chiral purity of the product was determined by chiral HPLC on a Chiralcel OJ—H column, and afforded ee% > 99%. The specific rotation of the tartrate salt is [a]_D + 55.7° (c = 2, H₂O), and the specific rotations for the corresponding corresponding free base and HCl salt are [a]_D + 3.6° (c = 2, EtOH) and [a]_D + 75.9° (c = 1, H₂O), respectively.

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local procedures.

Figures top

Fig. 1. A view of the molecules with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

(S)-1-(2-Chlorophenyl)-2-oxocyclohexan-1-aminium D-tartrate top

Crystal data top

C₁₂H₁₅ClNO⁺·C₄H₅O₆⁻	F(000) = 784
M_r = 373.78	D_x = 1.465 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2155 reflections
a = 7.1411 (2) Å	θ = 1.0–27.5°
b = 9.9878 (4) Å	µ = 0.27 mm⁻¹
c = 23.7530 (11) Å	T = 90 K
V = 1694.16 (11) Å³	Plate, colourless
Z = 4	0.20 × 0.20 × 0.03 mm

Data collection top

Nonius KappaCCD diffractometer	2986 independent reflections
Radiation source: fine-focus sealed tube	1519 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.110
Detector resolution: 9.1 pixels mm^-1	θ_max = 25.0°, θ_min = 1.7°
ω scans at fixed χ = 55°	h = −8→8
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −11→11
T_min = 0.949, T_max = 0.992	l = −27→28
13735 measured reflections

Refinement top

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)] = 0.060	H-atom parameters constrained
wR(F²) = 0.139	w = 1/[σ²(F_o²) + (0.0568P)²] where P = (F_o² + 2F_c²)/3
S = 0.96	(Δ/σ)_max < 0.001
2986 reflections	Δρ_max = 0.28 e Å⁻³
230 parameters	Δρ_min = −0.27 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 1241 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.10 (10)

Crystal data top

C₁₂H₁₅ClNO⁺·C₄H₅O₆⁻	V = 1694.16 (11) Å³
M_r = 373.78	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 7.1411 (2) Å	µ = 0.27 mm⁻¹
b = 9.9878 (4) Å	T = 90 K
c = 23.7530 (11) Å	0.20 × 0.20 × 0.03 mm

Data collection top

Nonius KappaCCD diffractometer	2986 independent reflections
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	1519 reflections with I > 2σ(I)
T_min = 0.949, T_max = 0.992	R_int = 0.110
13735 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.060	H-atom parameters constrained
wR(F²) = 0.139	Δρ_max = 0.28 e Å⁻³
S = 0.96	Δρ_min = −0.27 e Å⁻³
2986 reflections	Absolute structure: Flack (1983), 1241 Friedel pairs
230 parameters	Absolute structure parameter: 0.10 (10)
0 restraints

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 > 2σ(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
Cl1	0.3664 (2)	0.71723 (16)	0.91603 (9)	0.0776 (7)
O1	0.4054 (5)	0.4009 (4)	0.92986 (16)	0.0391 (11)
N1	0.5914 (5)	0.4734 (4)	0.83868 (16)	0.0254 (12)
H1A	0.6786	0.4352	0.8158	0.038*
H1B	0.5453	0.5485	0.8220	0.038*
H1C	0.4964	0.4144	0.8448	0.038*
C1	0.5939 (7)	0.7596 (6)	0.8988 (2)	0.0418 (17)
C2	0.6335 (10)	0.8933 (6)	0.8922 (3)	0.057 (2)
H2	0.5381	0.9585	0.8973	0.069*
C3	0.8128 (10)	0.9322 (6)	0.8779 (2)	0.0449 (18)
H3	0.8403	1.0242	0.8720	0.054*
C4	0.9520 (9)	0.8374 (6)	0.8723 (2)	0.0339 (15)
H4	1.0764	0.8643	0.8638	0.041*
C5	0.9097 (7)	0.7021 (5)	0.8790 (2)	0.0282 (15)
H5	1.0058	0.6375	0.8740	0.034*
C6	0.7292 (7)	0.6595 (5)	0.8931 (2)	0.0246 (14)
C7	0.6805 (7)	0.5100 (5)	0.8940 (2)	0.0226 (13)
C8	0.8535 (7)	0.4174 (5)	0.9031 (2)	0.0291 (14)
H8A	0.8155	0.3229	0.8978	0.035*
H8B	0.9501	0.4387	0.8746	0.035*
C9	0.9367 (8)	0.4348 (6)	0.9620 (2)	0.0399 (16)
H9A	1.0470	0.3756	0.9662	0.048*
H9B	0.9791	0.5285	0.9669	0.048*
C10	0.7954 (9)	0.4015 (6)	1.0067 (2)	0.0489 (18)
H10A	0.8503	0.4184	1.0443	0.059*
H10B	0.7626	0.3054	1.0043	0.059*
C11	0.6186 (9)	0.4861 (7)	0.9995 (2)	0.0505 (19)
H11A	0.5231	0.4588	1.0274	0.061*
H11B	0.6481	0.5819	1.0055	0.061*
C12	0.5447 (9)	0.4655 (5)	0.9409 (2)	0.0321 (14)
C13	0.5503 (8)	0.6596 (5)	0.6984 (3)	0.0266 (14)
C14	0.7637 (7)	0.6537 (5)	0.6976 (2)	0.0242 (14)
H14	0.8039	0.5662	0.7141	0.029*
C15	0.8443 (7)	0.7649 (5)	0.7331 (2)	0.0218 (13)
H15	0.7942	0.7538	0.7721	0.026*
C16	1.0558 (8)	0.7639 (6)	0.7370 (2)	0.0255 (14)
O2	0.8330 (5)	0.6619 (4)	0.64159 (14)	0.0297 (10)
H2A	0.7541	0.7012	0.6212	0.045*
O3	0.4634 (5)	0.6867 (3)	0.65555 (16)	0.0291 (10)
O4	0.4745 (5)	0.6434 (3)	0.74860 (16)	0.0334 (10)
O5	0.7747 (5)	0.8881 (3)	0.71191 (15)	0.0287 (10)
H5A	0.8366	0.9517	0.7257	0.043*
O6	1.1301 (5)	0.6502 (3)	0.74840 (16)	0.0304 (9)
H6	1.2464	0.6547	0.7436	0.046*
O7	1.1404 (5)	0.8705 (3)	0.72982 (14)	0.0269 (9)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0331 (10)	0.0394 (9)	0.160 (2)	0.0090 (9)	0.0157 (11)	−0.0109 (12)
O1	0.029 (3)	0.038 (2)	0.050 (3)	−0.0149 (19)	0.003 (2)	−0.008 (2)
N1	0.025 (3)	0.019 (2)	0.032 (3)	0.001 (2)	0.000 (2)	−0.002 (2)
C1	0.031 (4)	0.027 (4)	0.068 (5)	0.004 (3)	−0.004 (3)	−0.005 (3)
C2	0.045 (4)	0.030 (4)	0.096 (6)	0.009 (4)	−0.009 (4)	−0.008 (4)
C3	0.066 (5)	0.026 (4)	0.042 (4)	−0.011 (4)	−0.025 (4)	−0.004 (3)
C4	0.041 (4)	0.033 (4)	0.028 (3)	−0.009 (3)	0.003 (3)	0.003 (3)
C5	0.030 (4)	0.029 (4)	0.026 (3)	−0.006 (3)	−0.002 (3)	0.001 (3)
C6	0.031 (3)	0.026 (3)	0.017 (3)	−0.001 (3)	−0.001 (3)	0.000 (3)
C7	0.024 (3)	0.021 (3)	0.023 (3)	−0.005 (3)	−0.005 (3)	−0.001 (3)
C8	0.030 (3)	0.021 (3)	0.036 (4)	0.001 (3)	−0.005 (3)	0.005 (3)
C9	0.043 (4)	0.037 (4)	0.040 (4)	0.000 (3)	−0.004 (4)	0.010 (3)
C10	0.053 (5)	0.055 (5)	0.039 (4)	−0.008 (4)	−0.010 (4)	0.010 (4)
C11	0.056 (5)	0.068 (5)	0.027 (4)	−0.013 (4)	0.016 (4)	−0.004 (4)
C12	0.035 (4)	0.028 (4)	0.033 (4)	0.009 (3)	0.005 (3)	−0.001 (3)
C13	0.023 (3)	0.014 (3)	0.043 (4)	−0.003 (3)	−0.007 (3)	0.005 (3)
C14	0.023 (3)	0.022 (3)	0.028 (4)	−0.002 (3)	0.002 (3)	0.010 (3)
C15	0.018 (3)	0.023 (3)	0.025 (3)	0.003 (3)	0.001 (3)	0.003 (3)
C16	0.031 (4)	0.030 (4)	0.016 (3)	0.006 (3)	0.007 (3)	0.001 (3)
O2	0.030 (2)	0.031 (2)	0.028 (2)	0.004 (2)	−0.0047 (19)	−0.0057 (18)
O3	0.025 (2)	0.022 (2)	0.040 (2)	0.0016 (18)	−0.012 (2)	0.0039 (19)
O4	0.027 (2)	0.035 (2)	0.039 (2)	−0.0003 (19)	−0.005 (2)	0.010 (2)
O5	0.028 (2)	0.014 (2)	0.044 (2)	0.0049 (17)	−0.0106 (19)	−0.0062 (19)
O6	0.013 (2)	0.027 (2)	0.052 (3)	0.0024 (19)	0.002 (2)	0.010 (2)
O7	0.027 (2)	0.023 (2)	0.031 (2)	−0.0046 (19)	0.0049 (19)	0.0026 (18)

Geometric parameters (Å, º) top

Cl1—C1	1.728 (6)	C9—H9A	0.9900
O1—C12	1.214 (6)	C9—H9B	0.9900
N1—C7	1.505 (6)	C10—C11	1.529 (8)
N1—H1A	0.9100	C10—H10A	0.9900
N1—H1B	0.9100	C10—H10B	0.9900
N1—H1C	0.9100	C11—C12	1.503 (8)
C1—C2	1.374 (8)	C11—H11A	0.9900
C1—C6	1.397 (7)	C11—H11B	0.9900
C2—C3	1.380 (8)	C13—O3	1.223 (6)
C2—H2	0.9500	C13—O4	1.320 (6)
C3—C4	1.379 (7)	C13—C14	1.525 (7)
C3—H3	0.9500	C14—O2	1.423 (5)
C4—C5	1.393 (7)	C14—C15	1.508 (6)
C4—H4	0.9500	C14—H14	1.0000
C5—C6	1.398 (7)	C15—O5	1.419 (5)
C5—H5	0.9500	C15—C16	1.513 (6)
C6—C7	1.533 (7)	C15—H15	1.0000
C7—C12	1.542 (7)	C16—O7	1.237 (6)
C7—C8	1.558 (7)	C16—O6	1.282 (6)
C8—C9	1.531 (7)	O2—H2A	0.8400
C8—H8A	0.9900	O5—H5A	0.8400
C8—H8B	0.9900	O6—H6	0.8400
C9—C10	1.501 (7)

C7—N1—H1A	109.5	C10—C9—H9B	109.4
C7—N1—H1B	109.5	C8—C9—H9B	109.4
H1A—N1—H1B	109.5	H9A—C9—H9B	108.0
C7—N1—H1C	109.5	C9—C10—C11	110.7 (5)
H1A—N1—H1C	109.5	C9—C10—H10A	109.5
H1B—N1—H1C	109.5	C11—C10—H10A	109.5
C2—C1—C6	122.9 (6)	C9—C10—H10B	109.5
C2—C1—Cl1	117.3 (5)	C11—C10—H10B	109.5
C6—C1—Cl1	119.8 (4)	H10A—C10—H10B	108.1
C1—C2—C3	119.5 (6)	C12—C11—C10	108.5 (5)
C1—C2—H2	120.2	C12—C11—H11A	110.0
C3—C2—H2	120.2	C10—C11—H11A	110.0
C4—C3—C2	119.9 (6)	C12—C11—H11B	110.0
C4—C3—H3	120.0	C10—C11—H11B	110.0
C2—C3—H3	120.0	H11A—C11—H11B	108.4
C3—C4—C5	119.9 (6)	O1—C12—C11	124.0 (6)
C3—C4—H4	120.1	O1—C12—C7	120.9 (5)
C5—C4—H4	120.1	C11—C12—C7	114.1 (5)
C4—C5—C6	121.5 (5)	O3—C13—O4	124.8 (5)
C4—C5—H5	119.2	O3—C13—C14	120.4 (5)
C6—C5—H5	119.2	O4—C13—C14	114.6 (5)
C1—C6—C5	116.3 (5)	O2—C14—C15	110.3 (4)
C1—C6—C7	122.6 (5)	O2—C14—C13	110.9 (4)
C5—C6—C7	120.6 (5)	C15—C14—C13	110.3 (5)
N1—C7—C6	108.6 (4)	O2—C14—H14	108.4
N1—C7—C12	107.1 (4)	C15—C14—H14	108.4
C6—C7—C12	115.7 (4)	C13—C14—H14	108.4
N1—C7—C8	108.2 (4)	O5—C15—C14	107.9 (4)
C6—C7—C8	113.6 (4)	O5—C15—C16	112.2 (4)
C12—C7—C8	103.2 (4)	C14—C15—C16	114.3 (4)
C9—C8—C7	111.5 (4)	O5—C15—H15	107.4
C9—C8—H8A	109.3	C14—C15—H15	107.4
C7—C8—H8A	109.3	C16—C15—H15	107.4
C9—C8—H8B	109.3	O7—C16—O6	126.1 (5)
C7—C8—H8B	109.3	O7—C16—C15	118.3 (5)
H8A—C8—H8B	108.0	O6—C16—C15	115.6 (5)
C10—C9—C8	111.1 (5)	C14—O2—H2A	109.5
C10—C9—H9A	109.4	C15—O5—H5A	109.5
C8—C9—H9A	109.4	C16—O6—H6	109.5

C6—C1—C2—C3	1.5 (10)	C9—C10—C11—C12	55.6 (7)
Cl1—C1—C2—C3	−179.4 (5)	C10—C11—C12—O1	107.0 (6)
C1—C2—C3—C4	−2.1 (10)	C10—C11—C12—C7	−61.8 (6)
C2—C3—C4—C5	2.2 (9)	N1—C7—C12—O1	6.8 (6)
C3—C4—C5—C6	−1.8 (8)	C6—C7—C12—O1	128.1 (5)
C2—C1—C6—C5	−1.0 (8)	C8—C7—C12—O1	−107.2 (5)
Cl1—C1—C6—C5	179.9 (4)	N1—C7—C12—C11	175.9 (5)
C2—C1—C6—C7	−173.0 (5)	C6—C7—C12—C11	−62.8 (6)
Cl1—C1—C6—C7	7.9 (7)	C8—C7—C12—C11	61.9 (6)
C4—C5—C6—C1	1.2 (8)	O3—C13—C14—O2	−9.2 (7)
C4—C5—C6—C7	173.3 (5)	O4—C13—C14—O2	175.6 (4)
C1—C6—C7—N1	75.1 (6)	O3—C13—C14—C15	113.3 (5)
C5—C6—C7—N1	−96.5 (5)	O4—C13—C14—C15	−61.9 (6)
C1—C6—C7—C12	−45.3 (7)	O2—C14—C15—O5	65.8 (5)
C5—C6—C7—C12	143.0 (5)	C13—C14—C15—O5	−57.0 (6)
C1—C6—C7—C8	−164.5 (5)	O2—C14—C15—C16	−59.7 (6)
C5—C6—C7—C8	23.9 (6)	C13—C14—C15—C16	177.5 (5)
N1—C7—C8—C9	−172.2 (4)	O5—C15—C16—O7	9.9 (7)
C6—C7—C8—C9	67.1 (6)	C14—C15—C16—O7	133.1 (5)
C12—C7—C8—C9	−59.0 (5)	O5—C15—C16—O6	−170.8 (4)
C7—C8—C9—C10	59.8 (6)	C14—C15—C16—O6	−47.6 (6)
C8—C9—C10—C11	−56.0 (7)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O7ⁱ	0.91	1.81	2.715 (5)	176
N1—H1B···O4	0.91	2.05	2.856 (5)	147
N1—H1C···O1	0.91	2.13	2.642 (5)	115
N1—H1C···O3ⁱⁱ	0.91	2.29	2.893 (5)	123
N1—H1C···O5ⁱⁱ	0.91	2.37	3.001 (5)	126
O2—H2A···O3	0.84	2.24	2.672 (5)	112
O2—H2A···O1ⁱⁱⁱ	0.84	2.60	3.388 (5)	157
O5—H5A···O6^iv	0.84	2.09	2.864 (5)	153
O6—H6···O4^v	0.84	1.64	2.460 (5)	166
O6—H6···O3^v	0.84	2.62	3.265 (5)	134

Symmetry codes: (i) −x+2, y−1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2; (iii) −x+1, 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	C₁₂H₁₅ClNO⁺·C₄H₅O₆⁻
M_r	373.78
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	90
a, b, c (Å)	7.1411 (2), 9.9878 (4), 23.7530 (11)
V (Å³)	1694.16 (11)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.27
Crystal size (mm)	0.20 × 0.20 × 0.03

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 1997)
T_min, T_max	0.949, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	13735, 2986, 1519
R_int	0.110
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.060, 0.139, 0.96
No. of reflections	2986
No. of parameters	230
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.27
Absolute structure	Flack (1983), 1241 Friedel pairs
Absolute structure parameter	0.10 (10)

Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008) and local procedures.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O7ⁱ	0.91	1.81	2.715 (5)	176
N1—H1B···O4	0.91	2.05	2.856 (5)	147
N1—H1C···O1	0.91	2.13	2.642 (5)	115
N1—H1C···O3ⁱⁱ	0.91	2.29	2.893 (5)	123
N1—H1C···O5ⁱⁱ	0.91	2.37	3.001 (5)	126
O2—H2A···O3	0.84	2.24	2.672 (5)	112
O2—H2A···O1ⁱⁱⁱ	0.84	2.60	3.388 (5)	157
O5—H5A···O6^iv	0.84	2.09	2.864 (5)	153
O6—H6···O4^v	0.84	1.64	2.460 (5)	166
O6—H6···O3^v	0.84	2.62	3.265 (5)	134

Symmetry codes: (i) −x+2, y−1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2; (iii) −x+1, y+1/2, −z+3/2; (iv) −x+2, y+1/2, −z+3/2; (v) x+1, y, z.

Acknowledgements

The research was funded by the US Army Medical Research Material Command, Combat Casualty Care Research, Fort Detrick, MD contract W81XWH-06–1-0275 (MB) and by Yaupon Therapeutics, Inc. (MH, GZ, MS, SP and PAC).

References

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