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Acta Cryst. (2009). E65, o765-o766    [ doi:10.1107/S1600536809006990 ]

4-Aminopyridinium hydrogen succinate

H.-K. Fun, J. John, S. R. Jebas and T. Balasubramanian

Abstract top

In the title salt, C5H7N2+·C4H5O4-, the asymmetric unit comprises an aminopyridinium cation and a hydrogen succinate anion as protonation of the aromatic N atom of the 4-aminopyridine molecule has occurred. The crystal packing is stabilized by intermolecular O-H...O and N-H...O hydrogen bonds that lead to a two-dimensional array. Short C-H...O contacts are also present.

Comment top

4-Aminopyridine (Fampridine) is used clinically in Lambert-Eaton myasthenic syndrome and multiple sclerosis because by blocking potassium channels it prolongs action potentials thereby increasing transmitter release at the neuromuscular junction (Judge & Bever, (2006); Schwid et al., 1997; Strupp et al., 2004). The structure of 4-aminopyridine has been reported (Chao & Schempp, 1977) as has a redetermination (Anderson et al., 2005). Succinic acid is a dicarboxylic acid and is a precursor for many chemicals of industrial importance (Zeikus et al., 1999; Song & Lee, 2006). Succinic acid derivatives are mostly being used in chemicals, food and pharmaceuticals (Sauer et al., 2008). The crystal structure of succinic acid has also been reported (Gopalan et al., 2000; Leviel et al., 1981). As an extension of our systematic study of hydrogen bonding patterns of 4-aminopyridine with carboxylic acids, the title compound (I) has been synthesized and the crystal structure determined.

The asymmetric unit of (I) (Fig. 1) contains a 4-aminopyridinium cation and a succinic acetate anion, indicating that proton transfer occurred during the co-crystallisation experiment. Protonation leads to the widening of C2–N2–C3 angle in the pyridine ring to 120.7 (2)°, compared to 115.25 (13)° in 4-aminopyridine (Anderson et al., 2005). This type of protonation has been observed in various 4-aminopyridine acid complexes (Bhattacharya et al., 1994; Karle et al., 2003). Otherwise, the bond lengths and bond angles in 4-aminopyridinium cation are comparable to the values reported earlier for 4-aminopyridine (Chao & Schempp, 1977; Anderson et al., 2005). The 4-aminopyridine ring is essentially planar with the maximum deviation from planarity being -0.011 (3) Å for atom C5. The bond lengths and bond angles of the succinic acetate are found to have normal values (Gopalan et al., 2000; Leviel et al., 1981).

The crystal packing is consolidated by O—H···O and N—H···O intermolecular hydrogen bonds (Table 1) supported by C—H···O contacts. An intramolecular N—H···O hydrogen bond stabilises the conformation of the molecule. The molecules aggregate to form a 2-D array parallel to the ab-plane (Fig. 2).

Related literature top

For the biological activity of 4-aminopyridine, see: Judge & Bever (2006); Schwid et al. (1997); Strupp et al. (2004). For the applications of succinic acid, see: Sauer et al. (2008); Song & Lee (2006); Zeikus et al. (1999). For related structures, see: Chao & Schempp (1977); Anderson et al. (2005); Bhattacharya et al. (1994); Karle et al. (2003); Gopalan et al. (2000); Leviel et al., (1981). For stability of the temperature controller, see: Cosier & Glazer (1986).

Experimental top

Equimolar quantities of 4-aminopyridine (0.094 g, 1 mmol) and succinic acid (0.118 g, 1 mmol) were dissolved in ethanol (10 ml) and water (10 ml), respectively. The aqueous solution of succinic acid was added drop wise to the solution of 4-aminopyridine and stirred well for 4 h. The solution is refluxed at 343°K for 6 h. Colourless crystals were harvested after one month of solvent evaporation.

Refinement top

The N-bound H atoms were located from the Fourier map and are allowed to refine freely (N-H = 0.85 - 0.94 (3) Å). The O-bound H atom was located from the Fourier map and fixed in that position, with O—H = 1.09 Å, and allowed to refine with Uiso(H) = 1.2Ueq(O). All other H atoms were placed in calculated positions, with C—H = 0.93 — 0.97 Å, and refined using a riding model with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids and the atom numbering scheme. The dashed line indicates hydrogen bonding.
[Figure 2] Fig. 2. A 2-D supramolecular layer in (I), viewed along the c axis. Dashed lines indicate the hydrogen bonding.
4-Aminopyridinium hydrogen succinate top
Crystal data top
C5H7N2+·C4H5O4−F(000) = 448
Mr = 212.21Dx = 1.494 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 1804 reflections
a = 6.5443 (3) Åθ = 3.4–30.1°
b = 22.2867 (11) ŵ = 0.12 mm−1
c = 7.1112 (4) ÅT = 100 K
β = 114.587 (4)°Plate, colourless
V = 943.13 (8) Å30.38 × 0.14 × 0.08 mm
Z = 4
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer		2176 independent reflections
Radiation source: fine-focus sealed tube1483 reflections with I > 2σ(I)
graphiteRint = 0.066
φ and ω scansθmax = 27.5°, θmin = 3.3°
Absorption correction: multi-scan
(SADABS; Bruker, 2005)		h = −8→8
Tmin = 0.956, Tmax = 0.991k = −28→28
7174 measured reflectionsl = −9→8
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)] = 0.062Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.150H atoms treated by a mixture of independent and constrained refinement
S = 1.06 w = 1/[σ2(Fo2) + (0.0786P)2]
where P = (Fo2 + 2Fc2)/3
2176 reflections(Δ/σ)max = 0.001
148 parametersΔρmax = 0.44 e Å−3
0 restraintsΔρmin = −0.46 e Å−3
Crystal data top
C5H7N2+·C4H5O4−V = 943.13 (8) Å3
Mr = 212.21Z = 4
Monoclinic, P21/cMo Kα radiation
a = 6.5443 (3) ŵ = 0.12 mm−1
b = 22.2867 (11) ÅT = 100 K
c = 7.1112 (4) Å0.38 × 0.14 × 0.08 mm
β = 114.587 (4)°
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer		2176 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2005)		1483 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.991Rint = 0.066
7174 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.062H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.150Δρmax = 0.44 e Å−3
S = 1.06Δρmin = −0.46 e Å−3
2176 reflectionsAbsolute structure: ?
148 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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
O1−0.1281 (3)0.19522 (7)0.2994 (3)0.0174 (4)
O2−0.4204 (3)0.24560 (7)0.2995 (3)0.0153 (4)
O30.4285 (3)0.34855 (7)0.2828 (3)0.0176 (4)
O40.1374 (3)0.40250 (7)0.2633 (3)0.0189 (4)
N1−0.2764 (4)0.44695 (9)0.2808 (3)0.0171 (5)
N2−0.4551 (3)0.62442 (9)0.2152 (3)0.0151 (5)
C1−0.5396 (4)0.52400 (10)0.2605 (4)0.0151 (5)
H1A−0.63690.49620.27690.018*
C2−0.5929 (4)0.58295 (10)0.2401 (4)0.0155 (5)
H2A−0.72720.59530.24320.019*
C3−0.2614 (4)0.60783 (10)0.2064 (4)0.0156 (5)
H3A−0.17010.63680.18640.019*
C4−0.1974 (4)0.54940 (10)0.2261 (4)0.0159 (5)
H4A−0.06320.53870.21950.019*
C5−0.3347 (4)0.50458 (10)0.2570 (4)0.0132 (5)
C6−0.2223 (4)0.24291 (10)0.3003 (4)0.0124 (5)
C7−0.1087 (4)0.30270 (9)0.3032 (4)0.0119 (5)
H7A−0.20010.32510.17980.014*
H7B−0.10020.32570.42200.014*
C80.1262 (4)0.29562 (10)0.3127 (4)0.0124 (5)
H8A0.22300.27860.44580.015*
H8B0.12060.26740.20670.015*
C90.2288 (4)0.35388 (10)0.2832 (4)0.0136 (5)
H1O30.49010.30320.28380.016*
H1N1−0.378 (4)0.4190 (13)0.292 (4)0.020 (7)*
H1N2−0.490 (5)0.6636 (14)0.204 (4)0.027 (8)*
H2N1−0.155 (5)0.4361 (11)0.273 (4)0.013 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0163 (9)0.0058 (8)0.0317 (11)−0.0004 (6)0.0114 (8)−0.0008 (7)
O20.0120 (8)0.0061 (8)0.0294 (11)−0.0011 (6)0.0102 (8)0.0000 (6)
O30.0139 (9)0.0067 (8)0.0366 (12)0.0003 (6)0.0149 (8)0.0014 (7)
O40.0182 (9)0.0057 (8)0.0358 (12)0.0021 (6)0.0141 (8)0.0021 (7)
N10.0141 (10)0.0079 (10)0.0326 (14)0.0014 (8)0.0131 (10)0.0008 (8)
N20.0170 (11)0.0035 (10)0.0235 (13)0.0024 (7)0.0071 (9)0.0001 (8)
C10.0144 (12)0.0104 (12)0.0225 (15)−0.0008 (8)0.0096 (11)0.0020 (9)
C20.0142 (12)0.0092 (12)0.0240 (15)0.0000 (8)0.0089 (11)0.0002 (9)
C30.0139 (12)0.0131 (12)0.0204 (14)−0.0026 (9)0.0076 (11)0.0010 (10)
C40.0125 (12)0.0111 (12)0.0255 (15)−0.0021 (8)0.0093 (11)−0.0014 (9)
C50.0147 (11)0.0092 (11)0.0137 (13)−0.0011 (8)0.0038 (10)−0.0012 (9)
C60.0128 (11)0.0082 (11)0.0162 (14)−0.0009 (8)0.0060 (10)0.0000 (9)
C70.0117 (11)0.0067 (11)0.0175 (14)0.0002 (8)0.0063 (10)0.0005 (9)
C80.0115 (11)0.0063 (11)0.0205 (14)−0.0005 (8)0.0076 (10)0.0004 (9)
C90.0122 (11)0.0107 (12)0.0195 (14)−0.0002 (8)0.0081 (11)−0.0001 (9)
Geometric parameters (Å, °) top
O1—C61.230 (3)C1—H1A0.9300
O2—C61.295 (3)C2—H2A0.9300
O3—C91.313 (3)C3—C41.357 (3)
O3—H1O31.0871C3—H3A0.9300
O4—C91.217 (3)C4—C51.420 (3)
N1—C51.331 (3)C4—H4A0.9300
N1—H1N10.94 (3)C6—C71.522 (3)
N1—H2N10.86 (3)C7—C81.519 (3)
N2—C31.347 (3)C7—H7A0.9700
N2—C21.354 (3)C7—H7B0.9700
N2—H1N20.90 (3)C8—C91.516 (3)
C1—C21.352 (3)C8—H8A0.9700
C1—C51.419 (3)C8—H8B0.9700
C9—O3—H1O3116.8N1—C5—C4122.1 (2)
C5—N1—H1N1118.3 (16)C1—C5—C4116.8 (2)
C5—N1—H2N1119.4 (17)O1—C6—O2122.88 (19)
H1N1—N1—H2N1122 (2)O1—C6—C7120.88 (19)
C3—N2—C2120.7 (2)O2—C6—C7116.24 (18)
C3—N2—H1N2118.4 (17)C8—C7—C6112.93 (18)
C2—N2—H1N2120.9 (17)C8—C7—H7A109.0
C2—C1—C5119.9 (2)C6—C7—H7A109.0
C2—C1—H1A120.1C8—C7—H7B109.0
C5—C1—H1A120.1C6—C7—H7B109.0
C1—C2—N2121.4 (2)H7A—C7—H7B107.8
C1—C2—H2A119.3C9—C8—C7113.79 (18)
N2—C2—H2A119.3C9—C8—H8A108.8
N2—C3—C4121.0 (2)C7—C8—H8A108.8
N2—C3—H3A119.5C9—C8—H8B108.8
C4—C3—H3A119.5C7—C8—H8B108.8
C3—C4—C5120.2 (2)H8A—C8—H8B107.7
C3—C4—H4A119.9O4—C9—O3121.5 (2)
C5—C4—H4A119.9O4—C9—C8123.62 (19)
N1—C5—C1121.0 (2)O3—C9—C8114.91 (18)
C5—C1—C2—N20.3 (4)C3—C4—C5—C11.5 (4)
C3—N2—C2—C11.2 (4)O1—C6—C7—C8−2.1 (3)
C2—N2—C3—C4−1.3 (4)O2—C6—C7—C8177.7 (2)
N2—C3—C4—C5−0.1 (4)C6—C7—C8—C9171.3 (2)
C2—C1—C5—N1178.7 (2)C7—C8—C9—O43.3 (3)
C2—C1—C5—C4−1.6 (4)C7—C8—C9—O3−177.5 (2)
C3—C4—C5—N1−178.8 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H1O3···O2i1.091.402.482 (2)176
N1—H1N1···O3ii0.94 (3)2.00 (3)2.926 (3)168 (3)
N2—H1N2···O1iii0.90 (3)2.59 (3)3.115 (3)118 (3)
N2—H1N2···O2iii0.90 (3)1.92 (3)2.810 (3)174 (3)
N1—H2N1···O40.85 (3)2.08 (3)2.934 (3)175 (2)
C1—H1A···O4ii0.932.543.440 (3)164
C2—H2A···O1iii0.932.393.041 (3)127
C3—H3A···O1iv0.932.313.222 (3)166
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z; (iii) −x−1, y+1/2, −z+1/2; (iv) −x, y+1/2, −z+1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H1O3···O2i1.091.402.482 (2)176
N1—H1N1···O3ii0.94 (3)2.00 (3)2.926 (3)168 (3)
N2—H1N2···O1iii0.90 (3)2.59 (3)3.115 (3)118 (3)
N2—H1N2···O2iii0.90 (3)1.92 (3)2.810 (3)174 (3)
N1—H2N1···O40.85 (3)2.08 (3)2.934 (3)175 (2)
C1—H1A···O4ii0.932.543.440 (3)164
C2—H2A···O1iii0.932.393.041 (3)127
C3—H3A···O1iv0.932.313.222 (3)166
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z; (iii) −x−1, y+1/2, −z+1/2; (iv) −x, y+1/2, −z+1/2.
Acknowledgements top

HKF and SRJ thank the Malaysian Government and Universiti Sains Malaysia for Science Fund grant No. 305/PFIZIK/613312. SRJ thanks Universiti Sains Malaysia for a post–doctoral research fellowship. HKF also thanks Universiti Sains Malaysia for the Research University Golden Goose grant No.1001/PFIZIK/811012.

references
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