2-(4-Carb­oxy­piperidinium-1-yl)pyridine-3-carboxyl­ate

Fan, P.; Ge, C.; Sun, M.; Li, W.; Shang, R.

doi:10.1107/S1600536812005752

organic compounds

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Volume 68| Part 3| March 2012| Page o913

doi:10.1107/S1600536812005752

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2-(4-Carboxypiperidinium-1-yl)pyridine-3-carboxylate

Ping Fan,^a ^* Chunhua Ge,^a Mingjun Sun,^a Weiwei Li ^a and Runshan Shang ^a

^aCollege of Chemistry, Liaoning University, Shenyang 110036, People's Republic of China
^*Correspondence e-mail: pingfan@lnu.edu.cn

(Received 12 January 2012; accepted 9 February 2012; online 29 February 2012)

The title compound, C₁₂H₁₄N₂O₄, crystallizes as a zwitterion. A negative charge is delocalized in the deprotonated carboxyl group attached to the pyridine ring. The piperidine N atom accepts a proton and the ring is transformed into a piperidinium cation. There is an intramolecular N—H⋯O hydrogen bond between the protonated NH and a carboxylate O atom. In the crystal, an O—H⋯O hydrogen bond between the carboxyl group and the carboxylate O atom of another molecule generates a helix along the b axis.

Related literature

For the synthesis, see: Shreder et al. (2009 ); Léost et al. (1997 ); Bonnet et al. (2002 ).

Experimental

Crystal data

C₁₂H₁₄N₂O₄
M_r = 250.25
Monoclinic, P 2₁ /c
a = 7.1094 (14) Å
b = 18.667 (4) Å
c = 8.6603 (17) Å
β = 93.57 (3)°
V = 1147.1 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 293 K
0.20 × 0.20 × 0.20 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.964, T_max = 0.983
6010 measured reflections
2237 independent reflections
1841 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.118
S = 1.09
2237 reflections
168 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O1ⁱ	0.82	1.77	2.566 (2)	166
N2—H2A⋯O2	1.01 (2)	1.71 (2)	2.599 (2)	146.0 (16)
Symmetry code: (i) $[-x, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812005752/kp2382sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812005752/kp2382Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812005752/kp2382Isup3.cml

checkCIF report

Comment top

The title compound, 2-(4-carboxylpiperdinium-1-yl)pyridine-3-carboxylic acid is known as one of 2-chloronicotinic acid derivatives (Fig. 1). It has attracted a great deal of interest in recent years. A series of inhibitors of human neutrophil elastase have been synthesised based on this derivative. The piperidine ring is in a chair conformation. By the intramolecular N2—H2A···O2 hydrogen bond, the dihedral angle between the ring defined by N1/C2—C6 and the plane defined by N2/C8/C10 of piperidine is 70.3 °. The dihedral angle between the ring defined by N1/C2—C6 and the ring defined by C7—C9—C11 of piperidine is 71.6 °. Molecules are linked by intermolecular O—H···O hydrogen bonds to form a chain (Table 1, Fig. 2). There are weak π-π interactions (Fig. 2) with the plane to plane distances of 3.69 Å and 3.72 Å (x,3/2-y,-1/2+z; 3,372-y, 1/2+z] which result in the formation of supramolecular network.

Related literature top

For related literature [on what subject?], see: Shreder et al. (2009); Léost et al. (1997); Bonnet et al. (2002).

Experimental top

A mixture of 2-(4-methoxycarbonylpiperidin-1-yl)-3-pyridine formic acid ethyl ester (3.02 g, 10.7 mmol), NaOH (3.00 g, 75.0 mmol) and H₂O (50 mL) was heated at reflux for 4 h. After cooling, the pH of resulting mixture was adjusted to 4–5 with dilute hydrochloric acid. After 12 h, a lot of white solid was precipitated. The precipitate was filtrated and dried, yield 73.9%, mp 481.8-483.2 K. Single crystal of the title compound was obtained by evaporating a solution of above-mentioned solid (0.2 mmol) in 11 mL ethanol.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level(arbitrary sphere for the H atoms).
	Fig. 2. Packing diagram illustrating intra- and intermolecular hydrogen bonding interactions.

2-(4-Carboxypiperidinium-1-yl)pyridine-3-carboxylate top

Crystal data top

C₁₂H₁₄N₂O₄	F(000) = 528
M_r = 250.25	D_x = 1.449 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P2ybc	Cell parameters from 361 reflections
a = 7.1094 (14) Å	θ = 2.5–22.7°
b = 18.667 (4) Å	µ = 0.11 mm⁻¹
c = 8.6603 (17) Å	T = 293 K
β = 93.57 (3)°	Block, colourless
V = 1147.1 (4) Å³	0.20 × 0.20 × 0.20 mm
Z = 4

Data collection top

Bruker SMART CCD area-detector diffractometer	2237 independent reflections
Radiation source: fine-focus sealed tube	1841 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
ϕ and ω scans	θ_max = 26.0°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −8→8
T_min = 0.964, T_max = 0.983	k = −23→21
6010 measured reflections	l = −10→7

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.118	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ²(F_o²) + (0.0685P)² + 0.1385P] where P = (F_o² + 2F_c²)/3
2237 reflections	(Δ/σ)_max = 0.001
168 parameters	Δρ_max = 0.22 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Crystal data top

C₁₂H₁₄N₂O₄	V = 1147.1 (4) Å³
M_r = 250.25	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.1094 (14) Å	µ = 0.11 mm⁻¹
b = 18.667 (4) Å	T = 293 K
c = 8.6603 (17) Å	0.20 × 0.20 × 0.20 mm
β = 93.57 (3)°

Data collection top

Bruker SMART CCD area-detector diffractometer	2237 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	1841 reflections with I > 2σ(I)
T_min = 0.964, T_max = 0.983	R_int = 0.022
6010 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.118	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	Δρ_max = 0.22 e Å⁻³
2237 reflections	Δρ_min = −0.34 e Å⁻³
168 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
O4	0.06398 (16)	0.42630 (6)	0.56128 (13)	0.0431 (3)
N2	0.41209 (16)	0.63507 (6)	0.81715 (14)	0.0291 (3)
O3	−0.10491 (16)	0.44848 (6)	0.76521 (13)	0.0445 (3)
H3	−0.1719	0.4164	0.7277	0.067*
N1	0.68999 (17)	0.64666 (6)	0.98026 (15)	0.0373 (3)
O2	0.26774 (16)	0.75408 (6)	0.70841 (13)	0.0466 (3)
C3	0.55581 (18)	0.68088 (7)	0.89789 (16)	0.0278 (3)
C8	0.1114 (2)	0.56996 (8)	0.83901 (18)	0.0355 (4)
H8A	0.0488	0.6001	0.7604	0.043*
H8B	0.0187	0.5552	0.9102	0.043*
C12	0.0444 (2)	0.45637 (7)	0.68272 (17)	0.0314 (3)
O1	0.36031 (17)	0.85729 (6)	0.82086 (15)	0.0534 (4)
C7	0.2667 (2)	0.61218 (8)	0.92594 (17)	0.0357 (4)
H7A	0.2134	0.6541	0.9730	0.043*
H7B	0.3256	0.5828	1.0077	0.043*
C9	0.19275 (19)	0.50397 (7)	0.76289 (16)	0.0301 (3)
H9	0.2557	0.4754	0.8458	0.036*
C10	0.3436 (2)	0.52666 (8)	0.65609 (17)	0.0376 (4)
H10A	0.4004	0.4843	0.6136	0.045*
H10B	0.2858	0.5541	0.5707	0.045*
C2	0.53838 (18)	0.75479 (7)	0.88389 (16)	0.0288 (3)
C11	0.4954 (2)	0.57139 (8)	0.74008 (19)	0.0369 (4)
H11A	0.5636	0.5422	0.8174	0.044*
H11B	0.5842	0.5877	0.6670	0.044*
C1	0.3745 (2)	0.79174 (8)	0.79697 (18)	0.0352 (4)
C5	0.8281 (2)	0.76099 (9)	1.03995 (19)	0.0411 (4)
H5	0.9268	0.7873	1.0871	0.049*
C6	0.6822 (2)	0.79468 (8)	0.95705 (18)	0.0358 (4)
H6	0.6801	0.8444	0.9501	0.043*
C4	0.8245 (2)	0.68742 (9)	1.05140 (19)	0.0402 (4)
H4	0.9201	0.6649	1.1114	0.048*
H2A	0.344 (3)	0.6686 (11)	0.742 (2)	0.063 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0449 (6)	0.0350 (6)	0.0484 (7)	0.0028 (5)	−0.0044 (5)	−0.0133 (5)
N2	0.0281 (6)	0.0229 (6)	0.0362 (7)	−0.0020 (5)	−0.0001 (5)	0.0017 (5)
O3	0.0428 (6)	0.0447 (7)	0.0460 (7)	−0.0203 (5)	0.0027 (5)	−0.0074 (5)
N1	0.0333 (7)	0.0290 (7)	0.0483 (8)	0.0023 (5)	−0.0067 (6)	0.0049 (5)
O2	0.0421 (7)	0.0400 (6)	0.0551 (7)	0.0019 (5)	−0.0171 (6)	0.0043 (5)
C3	0.0244 (7)	0.0251 (7)	0.0340 (7)	−0.0014 (5)	0.0014 (6)	0.0008 (5)
C8	0.0297 (7)	0.0333 (8)	0.0438 (9)	−0.0055 (6)	0.0053 (6)	−0.0074 (6)
C12	0.0356 (8)	0.0207 (7)	0.0370 (8)	0.0022 (6)	−0.0039 (6)	0.0021 (6)
O1	0.0497 (7)	0.0295 (6)	0.0787 (9)	0.0131 (5)	−0.0153 (6)	−0.0008 (5)
C7	0.0333 (8)	0.0342 (8)	0.0404 (8)	−0.0071 (6)	0.0090 (6)	−0.0082 (6)
C9	0.0318 (7)	0.0257 (7)	0.0323 (7)	−0.0019 (6)	−0.0016 (6)	0.0019 (6)
C10	0.0390 (8)	0.0356 (8)	0.0389 (8)	−0.0056 (6)	0.0078 (7)	−0.0078 (6)
C2	0.0264 (7)	0.0252 (7)	0.0350 (8)	0.0014 (5)	0.0036 (6)	0.0008 (5)
C11	0.0328 (7)	0.0331 (8)	0.0457 (9)	−0.0026 (6)	0.0089 (6)	−0.0053 (7)
C1	0.0325 (7)	0.0302 (8)	0.0426 (8)	0.0039 (6)	−0.0006 (6)	0.0039 (6)
C5	0.0309 (8)	0.0379 (9)	0.0532 (10)	−0.0054 (6)	−0.0082 (7)	−0.0037 (7)
C6	0.0327 (7)	0.0257 (7)	0.0488 (9)	−0.0022 (6)	0.0006 (7)	−0.0010 (6)
C4	0.0303 (7)	0.0396 (9)	0.0491 (9)	0.0048 (6)	−0.0105 (7)	0.0037 (7)

Geometric parameters (Å, º) top

O4—C12	1.2079 (18)	C7—H7A	0.9700
N2—C3	1.4749 (17)	C7—H7B	0.9700
N2—C11	1.5030 (18)	C9—C10	1.519 (2)
N2—C7	1.5031 (18)	C9—H9	0.9800
N2—H2A	1.01 (2)	C10—C11	1.515 (2)
O3—C12	1.3240 (18)	C10—H10A	0.9700
O3—H3	0.8200	C10—H10B	0.9700
N1—C3	1.3200 (18)	C2—C6	1.386 (2)
N1—C4	1.342 (2)	C2—C1	1.514 (2)
O2—C1	1.2593 (18)	C11—H11A	0.9700
C3—C2	1.3897 (19)	C11—H11B	0.9700
C8—C7	1.518 (2)	C5—C6	1.376 (2)
C8—C9	1.528 (2)	C5—C4	1.377 (2)
C8—H8A	0.9700	C5—H5	0.9300
C8—H8B	0.9700	C6—H6	0.9300
C12—C9	1.5142 (19)	C4—H4	0.9300
O1—C1	1.2462 (18)

C3—N2—C11	112.86 (11)	C10—C9—H9	106.9
C3—N2—C7	110.53 (11)	C8—C9—H9	106.9
C11—N2—C7	111.03 (11)	C11—C10—C9	111.73 (12)
C3—N2—H2A	103.8 (11)	C11—C10—H10A	109.3
C11—N2—H2A	113.0 (11)	C9—C10—H10A	109.3
C7—N2—H2A	105.2 (11)	C11—C10—H10B	109.3
C12—O3—H3	109.5	C9—C10—H10B	109.3
C3—N1—C4	116.38 (13)	H10A—C10—H10B	107.9
N1—C3—C2	125.81 (13)	C6—C2—C3	115.73 (13)
N1—C3—N2	115.57 (12)	C6—C2—C1	120.38 (12)
C2—C3—N2	118.61 (12)	C3—C2—C1	123.88 (13)
C7—C8—C9	110.46 (12)	N2—C11—C10	111.12 (12)
C7—C8—H8A	109.6	N2—C11—H11A	109.4
C9—C8—H8A	109.6	C10—C11—H11A	109.4
C7—C8—H8B	109.6	N2—C11—H11B	109.4
C9—C8—H8B	109.6	C10—C11—H11B	109.4
H8A—C8—H8B	108.1	H11A—C11—H11B	108.0
O4—C12—O3	123.91 (14)	O1—C1—O2	126.68 (14)
O4—C12—C9	123.86 (13)	O1—C1—C2	115.64 (13)
O3—C12—C9	112.14 (12)	O2—C1—C2	117.68 (12)
N2—C7—C8	110.12 (12)	C6—C5—C4	118.46 (14)
N2—C7—H7A	109.6	C6—C5—H5	120.8
C8—C7—H7A	109.6	C4—C5—H5	120.8
N2—C7—H7B	109.6	C5—C6—C2	120.24 (14)
C8—C7—H7B	109.6	C5—C6—H6	119.9
H7A—C7—H7B	108.1	C2—C6—H6	119.9
C12—C9—C10	112.48 (11)	N1—C4—C5	123.25 (14)
C12—C9—C8	113.54 (12)	N1—C4—H4	118.4
C10—C9—C8	109.78 (11)	C5—C4—H4	118.4
C12—C9—H9	106.9

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.82	1.77	2.566 (2)	166
N2—H2A···O2	1.01 (2)	1.71 (2)	2.599 (2)	146.0 (16)

Symmetry code: (i) −x, y−1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₂H₁₄N₂O₄
M_r	250.25
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	7.1094 (14), 18.667 (4), 8.6603 (17)
β (°)	93.57 (3)
V (Å³)	1147.1 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.20 × 0.20 × 0.20

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.964, 0.983
No. of measured, independent and observed [I > 2σ(I)] reflections	6010, 2237, 1841
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.118, 1.09
No. of reflections	2237
No. of parameters	168
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.34

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.82	1.77	2.566 (2)	166
N2—H2A···O2	1.01 (2)	1.71 (2)	2.599 (2)	146.0 (16)

Symmetry code: (i) −x, y−1/2, −z+3/2.

Acknowledgements

This work was supported financially by the National Natural Science Foundation of China (grant Nos. 20971062 and 21171081), the Science Foundation of the Education Department of Liaoning Province (grant No. L2011007) and the Foundation of 211 Project for Innovative Talents Training, Liaoning University.

References

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Léost, F., Chantegrel, B. & Deshayes, C. (1997). Tetrahedron, 53, 7557–7576. Google Scholar
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