supplementary materials


su2343 scheme

Acta Cryst. (2012). E68, o86    [ doi:10.1107/S160053681105224X ]

2-{1-[(2-Nitrobenzenesulfonamido)methyl]cyclohexyl}acetic acid

N. Kanwal, E. Akbar Hussain, O. Sahin and O. Büyükgüngör

Abstract top

In the title compound, C15H20N2O6S, the C-SO2-NH-C torsion angle is 64.54 (14)°. In the molecule, there is a bifurcated N-H...(O,O) hydrogen bond, forming S(7) rings. In the crystal, inversion dimers are formed via O-H...O hydrogen bonds involving the carboxyl group, so forming R22(8) rings. These dimers are further linked via pairs of C-H...O hydrogen bonds, forming a C(6) chain propagating along the c-axis direction.

Comment top

The gabapentin, (systematic name: 2-[1-(aminomethyl)cyclohexyl]acetic acid), is used commercially as an anti-convulsant drug and was originally developed for the treatment of spasticity and partial epilepsy (Taylor et al., 1998; Cesena & Calcutt, 1999; Field et al., 2000). Various studies have been undertaken to investigate possible mechanisms of this drug's action. Stefani et al. (1998) were the first to demonstrate that gabapentin inhibits voltage-dependent Ca2+ channel currents recorded from cortical neurons. This ability of gabapentin to inhibit Ca2+ channels has also been demonstrated by number of other groups (Walker & De Waard, 1998; Martin et al., 2000; Sutton et al. 2002). However, the drug has poor oral bioavailability and is difficult to synthesize hence, SAR and structural studies on new derivatives of gabapentin is an attractive area of research in medicinal chemistry. Herein, we report on an efficient synthesis and the crystal structure of a new sulfonamide derivative of gabapentin.

The molecular structure of the title compound is shown in Fig. 1. The conformation of the N1—C9 bond in the C—SO2—NH—C segment has gauche torsions with respect to the SO bonds. The molecules are twisted at the S1 atom with the C10—S1—N1—C9 torsional angle being 64.54 (14)°. The dihedral angle between the sulfonyl benzene ring and the –SO2—NH—C (S1,N1,C9) segment is 86.07 (14)°. The values of the ring puckering parameters: QT = 0.555 (2) Å, θ = 175.8 (2)° and φ = 328 (3)° (Cremer & Pople, 1975), indicate that the cyclohexane ring has a chair conformation. As shown in Fig. 1 and Table 1, bifurcated intramolecular N1—H1···O3 and N1—H1···O6 hydrogen bonds produce S(7) rings (Bernstein et al., 1995).

In the crystal, hydroxyl O5 acts as a hydrogen-bond donor to the carbonly O atom, O6i, so forming an inversion dimer with an R22(8) ring (Table 1 and Fig. 2). As shown in Fig. 2, these dimers are further linked via a C-H···O interaction, so forming a C(6) chain running parallel to [001].

Related literature top

For commercial uses of gabapentin {systematic name: 2-[1-(aminomethyl)cyclohexyl]acetic acid}, see: Taylor et al. (1998); Cesena & Calcutt (1999); Field et al. (2000). For the ability of gabapentin to inhibit voltage-dependent Ca2+ channel currents, see: Stefani et al. (1998); Walker & De Waard (1998); Martin et al. (2000); Sutton et al. (2002). For the graph-set analysis of hydrogen-bond patterns, see: Bernstein et al. (1995). For ring puckering parameters, see: Cremer & Pople (1975).

Experimental top

Gabapentin (0.171 g, 1.00 mmol) was dissolved in distilled water (10 ml) in a round bottom flask (25 ml). The pH of the solution was maintained at 8–9 using 1 M Na2CO3 solution. The 2-nitrobenzenesulfonyl chloride (0.221 g, 1.00 mmol) was added to the above solution and stirred at room temperature. The reaction completion was monitored by TLC. Upon completion of the reaction the pH was adjusted 1–2, using 1 M HCl solution. The precipitate obtained was filtered, washed with distilled water, dried and recrystallized from methanol to yield colourless crystals.

Refinement top

The imine H atom was located from a difference Fourier map and was refined freely. All other H-atoms were included in calculated positions and refined using a riding model: O-H = 0.82 Å with Uiso(H) = 1.5Ueq(O), and C—H = 0.93 and 0.97 Å for H(aromatic) and H(methylene), respectively, with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2008); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. A view of the molecular structure of the title molecule, showing displacement ellipsoids drawn at the 30% probability level. Hydrogen bonds are indicated by dashed lines.
[Figure 2] Fig. 2. A view of the crystal packing of the title compound, showing the formation of the R22(8) rings, and the C(7) chain. For the sake of clarity, H atoms not involved in these motifs have been omitted [Symmetry codes: (i) -x+1, -y+1, -z; (ii) x, -y+1/2, z-1/2; see Table 1 for further details].
2-{1-[(2-Nitrobenzenesulfonamido)methyl]cyclohexyl}acetic acid top
Crystal data top
C15H20N2O6SF(000) = 752
Mr = 356.39Dx = 1.385 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 5311 reflections
a = 7.7383 (2) Åθ = 2.9–27.2°
b = 20.7319 (5) ŵ = 0.22 mm1
c = 11.9460 (3) ÅT = 296 K
β = 116.869 (1)°Block, colourless
V = 1709.59 (7) Å30.37 × 0.33 × 0.32 mm
Z = 4
Data collection top
Bruker APEXII CCD area-detector
diffractometer
3202 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.022
graphiteθmax = 28.3°, θmin = 2.0°
phi and ω scansh = 1010
17069 measured reflectionsk = 2727
4247 independent reflectionsl = 1515
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110H atoms treated by a mixture of independent and constrained refinement
S = 1.02 w = 1/[σ2(Fo2) + (0.0492P)2 + 0.4452P]
where P = (Fo2 + 2Fc2)/3
4247 reflections(Δ/σ)max < 0.001
221 parametersΔρmax = 0.29 e Å3
0 restraintsΔρmin = 0.32 e Å3
Crystal data top
C15H20N2O6SV = 1709.59 (7) Å3
Mr = 356.39Z = 4
Monoclinic, P21/cMo Kα radiation
a = 7.7383 (2) ŵ = 0.22 mm1
b = 20.7319 (5) ÅT = 296 K
c = 11.9460 (3) Å0.37 × 0.33 × 0.32 mm
β = 116.869 (1)°
Data collection top
Bruker APEXII CCD area-detector
diffractometer
3202 reflections with I > 2σ(I)
17069 measured reflectionsRint = 0.022
4247 independent reflectionsθmax = 28.3°
Refinement top
R[F2 > 2σ(F2)] = 0.040H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.110Δρmax = 0.29 e Å3
S = 1.02Δρmin = 0.32 e Å3
4247 reflectionsAbsolute structure: ?
221 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
xyzUiso*/Ueq
C10.2548 (2)0.54510 (7)0.24581 (13)0.0348 (3)
C20.1197 (2)0.59198 (8)0.14519 (15)0.0438 (4)
H2A0.17870.63440.16190.053*
H2B0.10590.57810.06400.053*
C30.0799 (3)0.59682 (9)0.13939 (18)0.0553 (4)
H3A0.15680.62830.07650.066*
H3B0.14490.55540.11530.066*
C40.0631 (3)0.61664 (10)0.2658 (2)0.0656 (5)
H4A0.00600.65930.28710.079*
H4B0.19120.61850.26150.079*
C50.0607 (3)0.56932 (10)0.36644 (19)0.0638 (5)
H5A0.00330.52770.34930.077*
H5B0.07430.58410.44710.077*
C60.2613 (3)0.56180 (9)0.37290 (15)0.0498 (4)
H6A0.33090.52810.43270.060*
H6B0.33270.60170.40360.060*
C70.4633 (2)0.55220 (8)0.26081 (15)0.0441 (4)
H7A0.50160.59710.27660.053*
H7B0.55090.52750.33330.053*
C80.4837 (2)0.52997 (8)0.14850 (17)0.0453 (4)
C90.1812 (2)0.47606 (7)0.20560 (14)0.0371 (3)
H9A0.05810.47080.20750.045*
H9B0.15950.46940.11990.045*
C100.0958 (2)0.31795 (7)0.19092 (14)0.0377 (3)
C110.1750 (2)0.27787 (7)0.13323 (14)0.0408 (3)
C120.0613 (3)0.23949 (8)0.03334 (17)0.0548 (4)
H120.11740.21250.00340.066*
C130.1371 (3)0.24136 (10)0.01188 (19)0.0648 (5)
H130.21550.21590.08020.078*
C140.2189 (3)0.28022 (10)0.0429 (2)0.0632 (5)
H140.35280.28130.01160.076*
C150.1039 (2)0.31806 (8)0.14452 (18)0.0510 (4)
H150.16100.34390.18230.061*
N10.3172 (2)0.42711 (6)0.28645 (14)0.0441 (3)
H10.398 (3)0.4174 (9)0.2660 (18)0.054 (6)*
N20.3849 (2)0.27452 (7)0.17499 (14)0.0516 (4)
O10.4004 (2)0.32564 (6)0.40392 (11)0.0645 (4)
O20.1074 (2)0.38599 (6)0.37366 (13)0.0643 (4)
O30.47073 (19)0.32459 (7)0.18100 (16)0.0724 (4)
O40.4618 (2)0.22220 (7)0.19748 (17)0.0839 (5)
O50.4434 (2)0.56977 (6)0.05920 (13)0.0641 (4)
H50.45960.55250.00300.096*
O60.5377 (2)0.47314 (6)0.14477 (13)0.0626 (4)
S10.23737 (6)0.364280 (19)0.32720 (4)0.04464 (13)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0359 (7)0.0320 (7)0.0359 (7)0.0062 (6)0.0158 (6)0.0050 (6)
C20.0451 (9)0.0381 (8)0.0469 (9)0.0023 (7)0.0198 (7)0.0030 (7)
C30.0440 (9)0.0509 (10)0.0682 (12)0.0051 (8)0.0230 (9)0.0021 (9)
C40.0558 (11)0.0621 (12)0.0900 (15)0.0012 (9)0.0428 (11)0.0182 (11)
C50.0784 (13)0.0681 (13)0.0635 (12)0.0116 (11)0.0485 (11)0.0197 (10)
C60.0591 (10)0.0487 (9)0.0400 (8)0.0074 (8)0.0210 (8)0.0110 (7)
C70.0372 (8)0.0401 (8)0.0523 (9)0.0092 (6)0.0177 (7)0.0065 (7)
C80.0384 (8)0.0411 (9)0.0626 (10)0.0053 (7)0.0283 (8)0.0014 (7)
C90.0385 (7)0.0343 (7)0.0366 (7)0.0066 (6)0.0152 (6)0.0046 (6)
C100.0450 (8)0.0285 (7)0.0408 (8)0.0020 (6)0.0206 (7)0.0038 (6)
C110.0466 (8)0.0328 (7)0.0427 (8)0.0001 (6)0.0200 (7)0.0026 (6)
C120.0744 (12)0.0411 (9)0.0476 (9)0.0029 (8)0.0265 (9)0.0061 (7)
C130.0679 (13)0.0529 (11)0.0524 (11)0.0158 (10)0.0084 (10)0.0034 (9)
C140.0453 (10)0.0577 (12)0.0723 (13)0.0093 (9)0.0140 (9)0.0066 (10)
C150.0471 (9)0.0443 (9)0.0654 (11)0.0011 (7)0.0287 (8)0.0048 (8)
N10.0445 (8)0.0330 (7)0.0547 (8)0.0023 (6)0.0223 (7)0.0002 (6)
N20.0531 (8)0.0444 (8)0.0598 (9)0.0074 (7)0.0277 (7)0.0005 (7)
O10.0750 (9)0.0464 (7)0.0474 (7)0.0032 (6)0.0059 (6)0.0072 (6)
O20.1011 (11)0.0500 (7)0.0670 (8)0.0077 (7)0.0603 (8)0.0054 (6)
O30.0548 (8)0.0564 (8)0.1159 (13)0.0022 (6)0.0474 (8)0.0012 (8)
O40.0726 (10)0.0507 (8)0.1188 (14)0.0237 (7)0.0347 (9)0.0021 (8)
O50.0783 (9)0.0592 (8)0.0755 (9)0.0146 (7)0.0530 (8)0.0136 (7)
O60.0811 (9)0.0444 (7)0.0816 (9)0.0067 (6)0.0537 (8)0.0045 (6)
S10.0601 (3)0.0345 (2)0.0397 (2)0.00341 (17)0.02283 (19)0.00003 (15)
Geometric parameters (Å, °) top
C1—C21.532 (2)C9—N11.467 (2)
C1—C91.5350 (19)C9—H9A0.9700
C1—C61.536 (2)C9—H9B0.9700
C1—C71.548 (2)C10—C151.386 (2)
C2—C31.518 (2)C10—C111.387 (2)
C2—H2A0.9700C10—S11.7779 (15)
C2—H2B0.9700C11—C121.372 (2)
C3—C41.513 (3)C11—N21.470 (2)
C3—H3A0.9700C12—C131.379 (3)
C3—H3B0.9700C12—H120.9300
C4—C51.512 (3)C13—C141.360 (3)
C4—H4A0.9700C13—H130.9300
C4—H4B0.9700C14—C151.380 (3)
C5—C61.527 (3)C14—H140.9300
C5—H5A0.9700C15—H150.9300
C5—H5B0.9700N1—S11.6084 (14)
C6—H6A0.9700N1—H10.790 (19)
C6—H6B0.9700N2—O41.2077 (19)
C7—C81.493 (2)N2—O31.2167 (19)
C7—H7A0.9700O1—S11.4244 (13)
C7—H7B0.9700O2—S11.4240 (13)
C8—O61.258 (2)O5—H50.8200
C8—O51.271 (2)
C2—C1—C9108.72 (12)H7A—C7—H7B107.7
C2—C1—C6109.79 (13)O6—C8—O5122.54 (16)
C9—C1—C6111.18 (12)O6—C8—C7119.54 (15)
C2—C1—C7109.67 (12)O5—C8—C7117.92 (15)
C9—C1—C7110.16 (12)N1—C9—C1112.64 (12)
C6—C1—C7107.29 (12)N1—C9—H9A109.1
C3—C2—C1113.41 (13)C1—C9—H9A109.1
C3—C2—H2A108.9N1—C9—H9B109.1
C1—C2—H2A108.9C1—C9—H9B109.1
C3—C2—H2B108.9H9A—C9—H9B107.8
C1—C2—H2B108.9C15—C10—C11117.76 (15)
H2A—C2—H2B107.7C15—C10—S1118.65 (13)
C4—C3—C2110.23 (15)C11—C10—S1123.43 (12)
C4—C3—H3A109.6C12—C11—C10121.73 (16)
C2—C3—H3A109.6C12—C11—N2116.35 (15)
C4—C3—H3B109.6C10—C11—N2121.92 (14)
C2—C3—H3B109.6C11—C12—C13119.16 (18)
H3A—C3—H3B108.1C11—C12—H12120.4
C5—C4—C3110.83 (15)C13—C12—H12120.4
C5—C4—H4A109.5C14—C13—C12120.38 (18)
C3—C4—H4A109.5C14—C13—H13119.8
C5—C4—H4B109.5C12—C13—H13119.8
C3—C4—H4B109.5C13—C14—C15120.32 (18)
H4A—C4—H4B108.1C13—C14—H14119.8
C4—C5—C6111.75 (16)C15—C14—H14119.8
C4—C5—H5A109.3C14—C15—C10120.63 (17)
C6—C5—H5A109.3C14—C15—H15119.7
C4—C5—H5B109.3C10—C15—H15119.7
C6—C5—H5B109.3C9—N1—S1120.04 (11)
H5A—C5—H5B107.9C9—N1—H1113.8 (14)
C5—C6—C1113.24 (14)S1—N1—H1110.6 (14)
C5—C6—H6A108.9O4—N2—O3123.53 (16)
C1—C6—H6A108.9O4—N2—C11118.41 (15)
C5—C6—H6B108.9O3—N2—C11118.01 (14)
C1—C6—H6B108.9C8—O5—H5109.5
H6A—C6—H6B107.7O2—S1—O1120.24 (9)
C8—C7—C1113.23 (12)O2—S1—N1107.30 (8)
C8—C7—H7A108.9O1—S1—N1107.49 (8)
C1—C7—H7A108.9O2—S1—C10106.03 (8)
C8—C7—H7B108.9O1—S1—C10106.58 (7)
C1—C7—H7B108.9N1—S1—C10108.81 (7)
C9—C1—C2—C369.39 (17)C10—C11—C12—C130.8 (3)
C6—C1—C2—C352.45 (18)N2—C11—C12—C13178.76 (16)
C7—C1—C2—C3170.10 (13)C11—C12—C13—C140.8 (3)
C1—C2—C3—C457.0 (2)C12—C13—C14—C150.2 (3)
C2—C3—C4—C557.7 (2)C13—C14—C15—C101.2 (3)
C3—C4—C5—C656.3 (2)C11—C10—C15—C141.1 (2)
C4—C5—C6—C153.1 (2)S1—C10—C15—C14176.65 (14)
C2—C1—C6—C550.00 (18)C1—C9—N1—S1139.40 (12)
C9—C1—C6—C570.36 (18)C12—C11—N2—O452.4 (2)
C7—C1—C6—C5169.12 (15)C10—C11—N2—O4128.05 (18)
C2—C1—C7—C867.57 (17)C12—C11—N2—O3125.20 (18)
C9—C1—C7—C852.07 (17)C10—C11—N2—O354.3 (2)
C6—C1—C7—C8173.23 (14)C9—N1—S1—O249.77 (14)
C1—C7—C8—O694.18 (18)C9—N1—S1—O1179.59 (12)
C1—C7—C8—O585.21 (18)C9—N1—S1—C1064.54 (14)
C2—C1—C9—N1171.39 (13)C15—C10—S1—O28.75 (15)
C6—C1—C9—N167.63 (17)C11—C10—S1—O2166.48 (13)
C7—C1—C9—N151.19 (17)C15—C10—S1—O1137.98 (13)
C15—C10—C11—C120.2 (2)C11—C10—S1—O137.26 (15)
S1—C10—C11—C12175.44 (13)C15—C10—S1—N1106.38 (13)
C15—C10—C11—N2179.68 (14)C11—C10—S1—N178.38 (14)
S1—C10—C11—N25.0 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O30.790 (19)2.362 (19)2.978 (2)135.6 (18)
N1—H1···O60.790 (19)2.455 (19)3.050 (2)133.0 (18)
O5—H5···O6i0.821.852.6595 (18)168
C12—H12···O2ii0.932.503.339 (2)151
Symmetry codes: (i) −x+1, −y+1, −z; (ii) x, −y+1/2, z−1/2.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
N1—H1···O30.790 (19)2.362 (19)2.978 (2)135.6 (18)
N1—H1···O60.790 (19)2.455 (19)3.050 (2)133.0 (18)
O5—H5···O6i0.821.852.6595 (18)168
C12—H12···O2ii0.932.503.339 (2)151
Symmetry codes: (i) −x+1, −y+1, −z; (ii) x, −y+1/2, z−1/2.
Acknowledgements top

The authors are grateful to the Department of Chemistry, GC University Lahore, Pakistan, for providing the diffractometer facility.

references
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