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Acta Cryst. (2008). E64, o1954    [ doi:10.1107/S1600536808029085 ]

(S)-(-)-6-(4-Bromophenyl)-2,3,5,6-tetrahydrothiazolo[2,3-b]imidazolium hydrogen oxalate

T. Minor and M. Chruszcz

Abstract top

The structure of the title compound, C11H12BrN2S+·C2HO4- (common name 6-bromolevamisole hydrogen oxalate), is stabilized mainly by hydrogen bonds. Hydrogen oxalate anions form parallel coplanar chains via O-H...O hydrogen bonds, while there are N-H...O hydrogen-bonding interactions between the 6-bromolevamisole cations and oxalate anions. Both five-membered rings from the 6-bromolevamisole molecule have a twist conformation. The molecule has an extended conformation, with the 4-bromophenyl substituent positioned equatorially with N-C-C-C and C-C-C-C torsion angles of 39.8 (3) and 100.4 (3)°, respectively.

Comment top

6-Bromolevamisole (Fig. 1) is a salt of a strong activator of cystic fibrosis conductance regulator (CTFR) chloride channels, including those in human airway epithelial cells. It shows a strong reduction in activity of Protein Phosphatases 2C and 2A, two of the most likely candidates for being a CTFR phosphatase (Luo et al., 2000). It has also been shown to inhibit alkaline phosphatases, including being an uncompetitive inhibitor of an alkaline phosphatase involved in sarcoma (Lee et al., 1975). Furthermore, since inhibitors affect alkaline phosphatase from the white blood cells of mothers of fetuses with Down's syndrome differently, the cation could be involved in screening for it (Denier et al., 2002).

Packing (Fig. 2) is stabilized by hydrogen bonds (Table 1). The oxalate ions form parallel, coplanar, one-dimensional chains via O—H···O hydrogen bonds, with each link in the chain having an N—H···O hydrogen bond from the deprotonated oxygen to the protonated nitrogen (N2) of the 6-bromolevamisole. The bromine also forms a short contact (3.111 Å) with the O3 (-1/2 + x, 1/2 - y, 2 - z) atom.

Related literature top

For background information, see: Denier et al. (2002); Lee et al. (1975); Luo et al. (2000).

Experimental top

6-Bromolevamisole oxalate was purchased from Sigma, and dissolved in a mixture of 1-butanol and DMSO in a 1:1 ratio. A single crystal suitable for X-ray diffraction study was obtained by slow evaporation at room temperature.

Refinement top

Hydrogen atoms attached to C7, C8, and C9 were placed in ideal positions, and refined using a riding-model approximation with C—H bond lengths of 0.98 Å in the case of C7 and 0.97 Å in the cases of C8 and C9. All other hydrogen atoms were located in a difference density Fourier map and refined with isotropic displacement parameters.

Computing details top

Data collection: HKL-2000 (Otwinowski & Minor, 1997); cell refinement: HKL-2000 (Otwinowski & Minor, 1997); data reduction: HKL-2000 (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008), HKL-3000SM (Minor et al., 2006); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008), HKL-3000SM (Minor et al., 2006); molecular graphics: HKL-3000SM (Minor et al., 2006), Mercury (Macrae et al., 2006), ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: HKL-3000SM (Minor et al., 2006).

Figures top
[Figure 1] Fig. 1. An asymmetric unit of the title compound. Displacement ellipsoids are drawn at the 50% probability level, while hydrogen atoms are drawn as spheres of an arbitrary radius.
[Figure 2] Fig. 2. A packing diagram with hydrogen bonds marked with blue, dashed lines. Short contacts between Br···O3 (-1/2 + x, 1/2 - y, 2 - z) are marked with red, dashed lines.
(S)-(-)-6-(4-Bromophenyl)-2,3,5,6-tetrahydrothiazolo[2,3- b]imidazolium hydrogen oxalate top
Crystal data top
C11H12BrN2S+·C2HO4−Dx = 1.643 Mg m−3
Mr = 373.22Melting point: 465 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71074 Å
Hall symbol: P 2ac 2abCell parameters from 39658 reflections
a = 5.615 (1) Åθ = 2.6–29.1°
b = 8.256 (1) ŵ = 2.88 mm−1
c = 32.539 (1) ÅT = 89 K
V = 1508.4 (3) Å3Needle, colourless
Z = 40.50 × 0.03 × 0.03 mm
F(000) = 752
Data collection top
Rigaku R-AXIS RAPID
diffractometer		4061 independent reflections
Radiation source: fine-focus sealed tube3438 reflections with I > 2σ(I)
graphiteRint = 0.081
Detector resolution: 10 pixels mm-1θmax = 29.1°, θmin = 2.6°
ω scans with χ offseth = −7→7
Absorption correction: multi-scan
(Otwinowski et al., 2003)		k = −11→11
Tmin = 0.90, Tmax = 0.92l = −44→44
39658 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.074 w = 1/[σ2(Fo2) + (0.0326P)2 + 0.8007P]
where P = (Fo2 + 2Fc2)/3
S = 1.10(Δ/σ)max = 0.001
4061 reflectionsΔρmax = 0.67 e Å−3
230 parametersΔρmin = −0.51 e Å−3
0 restraintsAbsolute structure: Flack (1983), 1686 Friedel pairs?
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.018 (7)
Crystal data top
C11H12BrN2S+·C2HO4−V = 1508.4 (3) Å3
Mr = 373.22Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.615 (1) ŵ = 2.88 mm−1
b = 8.256 (1) ÅT = 89 K
c = 32.539 (1) Å0.50 × 0.03 × 0.03 mm
Data collection top
Rigaku R-AXIS RAPID
diffractometer		4061 independent reflections
Absorption correction: multi-scan
(Otwinowski et al., 2003)		3438 reflections with I > 2σ(I)
Tmin = 0.90, Tmax = 0.92Rint = 0.081
39658 measured reflectionsθmax = 29.1°
Refinement top
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.074Δρmax = 0.67 e Å−3
S = 1.10Δρmin = −0.51 e Å−3
4061 reflectionsAbsolute structure: Flack (1983), 1686 Friedel pairs?
230 parametersFlack parameter: −0.018 (7)
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.32101 (6)0.56744 (4)1.059826 (8)0.03817 (9)
S10.35196 (13)0.49266 (9)0.76858 (2)0.02854 (14)
N20.2692 (4)0.4064 (3)0.84952 (6)0.0204 (4)
C110.2064 (4)0.4764 (3)0.81524 (7)0.0196 (5)
C70.0668 (4)0.4192 (3)0.87900 (7)0.0198 (5)
H7−0.02670.31900.87810.024*
N1−0.0024 (4)0.5521 (3)0.81664 (6)0.0201 (4)
C8−0.0808 (4)0.5585 (3)0.85977 (7)0.0211 (5)
H8A−0.25050.53870.86220.025*
H8B−0.04270.66200.87230.025*
C9−0.0363 (6)0.6744 (4)0.78469 (8)0.0261 (6)
C10.1407 (4)0.4519 (3)0.92285 (7)0.0208 (5)
C20.3255 (5)0.5587 (3)0.93230 (7)0.0247 (5)
C100.0970 (6)0.6059 (4)0.74766 (9)0.0329 (7)
C30.3820 (5)0.5913 (4)0.97307 (9)0.0307 (6)
C50.0649 (5)0.4154 (4)0.99535 (9)0.0313 (6)
C60.0123 (6)0.3807 (4)0.95449 (9)0.0288 (6)
C40.2489 (5)0.5198 (3)1.00383 (8)0.0272 (6)
O30.8027 (3)−0.0585 (2)0.84464 (5)0.0197 (3)
O40.6388 (3)0.1887 (2)0.84329 (6)0.0238 (4)
C1B0.6295 (4)0.0378 (3)0.84479 (7)0.0172 (5)
C2B0.3822 (4)−0.0442 (3)0.84594 (7)0.0186 (5)
O10.2089 (3)0.0602 (2)0.84707 (6)0.0279 (4)
O20.3598 (3)−0.1898 (2)0.84549 (7)0.0320 (5)
H20.405 (6)0.611 (4)0.9106 (11)0.040 (10)*
H5−0.032 (7)0.372 (5)1.0134 (12)0.051 (11)*
H10B0.158 (8)0.694 (5)0.7302 (12)0.058 (11)*
H9A−0.201 (7)0.684 (4)0.7791 (9)0.027 (8)*
H30.500 (7)0.655 (4)0.9791 (10)0.037 (9)*
H9B0.031 (6)0.780 (4)0.7948 (9)0.027 (8)*
H10A0.009 (7)0.530 (5)0.7315 (12)0.052 (11)*
H6−0.104 (7)0.305 (5)0.9487 (10)0.045 (10)*
H1O0.042 (9)0.012 (5)0.8512 (14)0.076 (15)*
H1N0.361 (7)0.327 (4)0.8501 (11)0.044 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0587 (2)0.03403 (15)0.02182 (11)0.00178 (15)−0.00718 (13)−0.00204 (11)
S10.0306 (3)0.0314 (3)0.0237 (3)0.0028 (3)0.0062 (3)−0.0047 (2)
N20.0192 (10)0.0191 (11)0.0230 (9)0.0027 (8)−0.0002 (8)−0.0023 (8)
C110.0207 (11)0.0133 (12)0.0248 (11)−0.0011 (9)−0.0004 (9)−0.0053 (8)
C70.0188 (11)0.0176 (12)0.0230 (11)0.0011 (10)0.0009 (9)−0.0003 (9)
N10.0192 (9)0.0205 (11)0.0206 (9)0.0028 (9)−0.0001 (7)−0.0001 (8)
C80.0186 (11)0.0235 (12)0.0212 (10)0.0031 (11)0.0009 (8)0.0011 (10)
C90.0315 (16)0.0259 (14)0.0209 (12)0.0032 (12)−0.0035 (11)0.0018 (10)
C10.0212 (12)0.0186 (12)0.0225 (10)0.0015 (10)−0.0018 (9)0.0009 (9)
C20.0248 (12)0.0240 (12)0.0254 (11)−0.0056 (12)0.0014 (10)−0.0017 (9)
C100.0430 (18)0.0332 (16)0.0225 (12)0.0072 (13)−0.0009 (12)−0.0022 (11)
C30.0328 (16)0.0310 (16)0.0282 (13)−0.0079 (12)−0.0028 (11)−0.0046 (11)
C50.0358 (15)0.0316 (16)0.0263 (12)−0.0052 (13)0.0022 (11)0.0044 (12)
C60.0315 (15)0.0262 (14)0.0285 (13)−0.0081 (12)−0.0030 (11)0.0025 (11)
C40.0369 (14)0.0251 (13)0.0195 (11)0.0047 (11)−0.0038 (10)0.0006 (9)
O30.0130 (7)0.0178 (7)0.0285 (8)0.0007 (7)0.0008 (6)−0.0009 (7)
O40.0174 (9)0.0172 (8)0.0368 (9)−0.0001 (7)−0.0003 (8)−0.0004 (7)
C1B0.0153 (10)0.0211 (13)0.0153 (9)0.0003 (9)0.0006 (8)−0.0010 (8)
C2B0.0153 (11)0.0214 (13)0.0191 (10)0.0004 (9)−0.0011 (8)−0.0012 (9)
O10.0113 (8)0.0192 (8)0.0532 (11)0.0004 (7)0.0000 (7)−0.0015 (9)
O20.0170 (9)0.0183 (9)0.0606 (13)−0.0004 (7)0.0001 (9)−0.0025 (9)
Geometric parameters (Å, °) top
Br1—C41.908 (3)C1—C21.396 (4)
S1—C111.729 (2)C2—C31.390 (3)
S1—C101.840 (3)C2—H20.94 (4)
N2—C111.305 (3)C10—H10B0.98 (4)
N2—C71.491 (3)C10—H10A0.96 (4)
N2—H1N0.83 (4)C3—C41.382 (4)
C11—N11.329 (3)C3—H30.87 (4)
C7—C11.510 (3)C5—C41.373 (4)
C7—C81.549 (3)C5—C61.392 (4)
C7—H70.9800C5—H50.88 (4)
N1—C91.461 (3)C6—H60.92 (4)
N1—C81.472 (3)O3—C1B1.257 (3)
C8—H8A0.9700O4—C1B1.248 (3)
C8—H8B0.9700C1B—C2B1.546 (3)
C9—C101.527 (4)C2B—O21.208 (3)
C9—H9A0.95 (4)C2B—O11.300 (3)
C9—H9B1.00 (3)O1—H1O1.03 (5)
C1—C61.387 (4)
C11—S1—C1089.80 (13)C2—C1—C7121.7 (2)
C11—N2—C7108.2 (2)C3—C2—C1120.2 (2)
C11—N2—H1N122 (2)C3—C2—H2121 (2)
C7—N2—H1N121 (3)C1—C2—H2118 (2)
N2—C11—N1114.6 (2)C9—C10—S1106.10 (19)
N2—C11—S1131.1 (2)C9—C10—H10B111 (2)
N1—C11—S1114.23 (18)S1—C10—H10B109 (3)
N2—C7—C1114.3 (2)C9—C10—H10A115 (2)
N2—C7—C8101.55 (19)S1—C10—H10A106 (2)
C1—C7—C8113.3 (2)H10B—C10—H10A110 (3)
N2—C7—H7109.1C4—C3—C2119.0 (3)
C1—C7—H7109.1C4—C3—H3121 (2)
C8—C7—H7109.1C2—C3—H3120 (2)
C11—N1—C9114.5 (2)C4—C5—C6118.7 (3)
C11—N1—C8108.2 (2)C4—C5—H5126 (3)
C9—N1—C8127.9 (2)C6—C5—H5115 (3)
N1—C8—C7101.46 (19)C1—C6—C5120.8 (3)
N1—C8—H8A111.5C1—C6—H6120 (2)
C7—C8—H8A111.5C5—C6—H6119 (2)
N1—C8—H8B111.5C5—C4—C3122.0 (3)
C7—C8—H8B111.5C5—C4—Br1118.7 (2)
H8A—C8—H8B109.3C3—C4—Br1119.3 (2)
N1—C9—C10104.0 (2)O4—C1B—O3126.8 (2)
N1—C9—H9A108.6 (19)O4—C1B—C2B118.5 (2)
C10—C9—H9A110.9 (18)O3—C1B—C2B114.69 (19)
N1—C9—H9B108.4 (17)O2—C2B—O1125.6 (2)
C10—C9—H9B113.1 (18)O2—C2B—C1B121.9 (2)
H9A—C9—H9B111 (3)O1—C2B—C1B112.4 (2)
C6—C1—C2119.3 (2)C2B—O1—H1O115 (3)
C6—C1—C7118.9 (2)
C7—N2—C11—N16.2 (3)N2—C7—C1—C239.8 (3)
C7—N2—C11—S1−175.80 (19)C8—C7—C1—C2−75.9 (3)
C10—S1—C11—N2179.2 (3)C6—C1—C2—C30.9 (4)
C10—S1—C11—N1−2.8 (2)C7—C1—C2—C3177.2 (2)
C11—N2—C7—C1−141.1 (2)N1—C9—C10—S1−32.9 (3)
C11—N2—C7—C8−18.8 (2)C11—S1—C10—C921.4 (2)
N2—C11—N1—C9159.8 (2)C1—C2—C3—C4−1.6 (4)
S1—C11—N1—C9−18.5 (3)C2—C1—C6—C50.4 (4)
N2—C11—N1—C810.3 (3)C7—C1—C6—C5−176.0 (3)
S1—C11—N1—C8−168.00 (17)C4—C5—C6—C1−0.9 (5)
C11—N1—C8—C7−21.0 (3)C6—C5—C4—C30.2 (4)
C9—N1—C8—C7−165.2 (2)C6—C5—C4—Br1180.0 (2)
N2—C7—C8—N123.0 (2)C2—C3—C4—C51.1 (4)
C1—C7—C8—N1146.1 (2)C2—C3—C4—Br1−178.7 (2)
C11—N1—C9—C1033.8 (3)O4—C1B—C2B—O2176.5 (2)
C8—N1—C9—C10176.1 (2)O3—C1B—C2B—O2−2.1 (3)
N2—C7—C1—C6−143.9 (3)O4—C1B—C2B—O1−3.0 (3)
C8—C7—C1—C6100.4 (3)O3—C1B—C2B—O1178.4 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O1—H1O···O3i1.03 (5)1.48 (5)2.483 (2)164 (4)
N2—H1N···O40.83 (4)1.95 (4)2.753 (3)163 (4)
N2—H1N···O10.83 (4)2.37 (4)2.879 (3)120 (3)
Symmetry codes: (i) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O1—H1O···O3i1.03 (5)1.48 (5)2.483 (2)164 (4)
N2—H1N···O40.83 (4)1.95 (4)2.753 (3)163 (4)
N2—H1N···O10.83 (4)2.37 (4)2.879 (3)120 (3)
Symmetry codes: (i) x−1, y, z.
Acknowledgements top

The authors thank Zbigniew Dauter for helpful discussions. This work was supported by contract No. GI11496 from HKL Research, Inc.

references
References top

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