organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

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[Shreder, K. R., Cajica, J., Du, L., Fraser, A., Hu, Y. & Kohno, Y. (2009). Bioorg. Med. Chem. Lett. 19, 4743-4746.]); Léost et al. (1997[Léost, F., Chantegrel, B. & Deshayes, C. (1997). Tetrahedron, 53, 7557-7576.]); Bonnet et al. (2002[Bonnet, V., Mongin, F., Trécourt, F., Quéguiner, G. & Knochel, P. (2002). Tetrahedron, 58, 4429-4438.]).

[Scheme 1]

Experimental

Crystal data
  • C12H14N2O4

  • Mr = 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[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.964, Tmax = 0.983

  • 6010 measured reflections

  • 2237 independent reflections

  • 1841 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.22 e Å−3

  • Δρmin = −0.34 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2001[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information


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.

Refinement top

H atoms attached to C atoms were positioned geometrically and refined using a riding model, with Csp3—H = 0.97 Å or Csp2—H = 0.93 Å and with Uiso(H) = 1.2Ueq(C). H atom attached to O atom was O—H = 0.82 Å and with Uiso(H) = 1.5Ueq(O). H atoms attached to N atom were located by difference Fourier synthesis and refined isotropically.

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
[Figure 1] Fig. 1. Molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level(arbitrary sphere for the H atoms).
[Figure 2] Fig. 2. Packing diagram illustrating intra- and intermolecular hydrogen bonding interactions.
2-(4-Carboxypiperidinium-1-yl)pyridine-3-carboxylate top
Crystal data top
C12H14N2O4F(000) = 528
Mr = 250.25Dx = 1.449 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P2ybcCell parameters from 361 reflections
a = 7.1094 (14) Åθ = 2.5–22.7°
b = 18.667 (4) ŵ = 0.11 mm1
c = 8.6603 (17) ÅT = 293 K
β = 93.57 (3)°Block, colourless
V = 1147.1 (4) Å30.20 × 0.20 × 0.20 mm
Z = 4
Data collection top
Bruker SMART CCD area-detector
diffractometer
2237 independent reflections
Radiation source: fine-focus sealed tube1841 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.022
ϕ and ω scansθmax = 26.0°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
h = 88
Tmin = 0.964, Tmax = 0.983k = 2321
6010 measured reflectionsl = 107
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)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.118H atoms treated by a mixture of independent and constrained refinement
S = 1.09 w = 1/[σ2(Fo2) + (0.0685P)2 + 0.1385P]
where P = (Fo2 + 2Fc2)/3
2237 reflections(Δ/σ)max = 0.001
168 parametersΔρmax = 0.22 e Å3
0 restraintsΔρmin = 0.34 e Å3
Crystal data top
C12H14N2O4V = 1147.1 (4) Å3
Mr = 250.25Z = 4
Monoclinic, P21/cMo Kα radiation
a = 7.1094 (14) ŵ = 0.11 mm1
b = 18.667 (4) ÅT = 293 K
c = 8.6603 (17) Å0.20 × 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)
Tmin = 0.964, Tmax = 0.983Rint = 0.022
6010 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0420 restraints
wR(F2) = 0.118H atoms treated by a mixture of independent and constrained refinement
S = 1.09Δρmax = 0.22 e Å3
2237 reflectionsΔρmin = 0.34 e Å3
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
xyzUiso*/Ueq
O40.06398 (16)0.42630 (6)0.56128 (13)0.0431 (3)
N20.41209 (16)0.63507 (6)0.81715 (14)0.0291 (3)
O30.10491 (16)0.44848 (6)0.76521 (13)0.0445 (3)
H30.17190.41640.72770.067*
N10.68999 (17)0.64666 (6)0.98026 (15)0.0373 (3)
O20.26774 (16)0.75408 (6)0.70841 (13)0.0466 (3)
C30.55581 (18)0.68088 (7)0.89789 (16)0.0278 (3)
C80.1114 (2)0.56996 (8)0.83901 (18)0.0355 (4)
H8A0.04880.60010.76040.043*
H8B0.01870.55520.91020.043*
C120.0444 (2)0.45637 (7)0.68272 (17)0.0314 (3)
O10.36031 (17)0.85729 (6)0.82086 (15)0.0534 (4)
C70.2667 (2)0.61218 (8)0.92594 (17)0.0357 (4)
H7A0.21340.65410.97300.043*
H7B0.32560.58281.00770.043*
C90.19275 (19)0.50397 (7)0.76289 (16)0.0301 (3)
H90.25570.47540.84580.036*
C100.3436 (2)0.52666 (8)0.65609 (17)0.0376 (4)
H10A0.40040.48430.61360.045*
H10B0.28580.55410.57070.045*
C20.53838 (18)0.75479 (7)0.88389 (16)0.0288 (3)
C110.4954 (2)0.57139 (8)0.74008 (19)0.0369 (4)
H11A0.56360.54220.81740.044*
H11B0.58420.58770.66700.044*
C10.3745 (2)0.79174 (8)0.79697 (18)0.0352 (4)
C50.8281 (2)0.76099 (9)1.03995 (19)0.0411 (4)
H50.92680.78731.08710.049*
C60.6822 (2)0.79468 (8)0.95705 (18)0.0358 (4)
H60.68010.84440.95010.043*
C40.8245 (2)0.68742 (9)1.05140 (19)0.0402 (4)
H40.92010.66491.11140.048*
H2A0.344 (3)0.6686 (11)0.742 (2)0.063 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O40.0449 (6)0.0350 (6)0.0484 (7)0.0028 (5)0.0044 (5)0.0133 (5)
N20.0281 (6)0.0229 (6)0.0362 (7)0.0020 (5)0.0001 (5)0.0017 (5)
O30.0428 (6)0.0447 (7)0.0460 (7)0.0203 (5)0.0027 (5)0.0074 (5)
N10.0333 (7)0.0290 (7)0.0483 (8)0.0023 (5)0.0067 (6)0.0049 (5)
O20.0421 (7)0.0400 (6)0.0551 (7)0.0019 (5)0.0171 (6)0.0043 (5)
C30.0244 (7)0.0251 (7)0.0340 (7)0.0014 (5)0.0014 (6)0.0008 (5)
C80.0297 (7)0.0333 (8)0.0438 (9)0.0055 (6)0.0053 (6)0.0074 (6)
C120.0356 (8)0.0207 (7)0.0370 (8)0.0022 (6)0.0039 (6)0.0021 (6)
O10.0497 (7)0.0295 (6)0.0787 (9)0.0131 (5)0.0153 (6)0.0008 (5)
C70.0333 (8)0.0342 (8)0.0404 (8)0.0071 (6)0.0090 (6)0.0082 (6)
C90.0318 (7)0.0257 (7)0.0323 (7)0.0019 (6)0.0016 (6)0.0019 (6)
C100.0390 (8)0.0356 (8)0.0389 (8)0.0056 (6)0.0078 (7)0.0078 (6)
C20.0264 (7)0.0252 (7)0.0350 (8)0.0014 (5)0.0036 (6)0.0008 (5)
C110.0328 (7)0.0331 (8)0.0457 (9)0.0026 (6)0.0089 (6)0.0053 (7)
C10.0325 (7)0.0302 (8)0.0426 (8)0.0039 (6)0.0006 (6)0.0039 (6)
C50.0309 (8)0.0379 (9)0.0532 (10)0.0054 (6)0.0082 (7)0.0037 (7)
C60.0327 (7)0.0257 (7)0.0488 (9)0.0022 (6)0.0006 (7)0.0010 (6)
C40.0303 (7)0.0396 (9)0.0491 (9)0.0048 (6)0.0105 (7)0.0037 (7)
Geometric parameters (Å, º) top
O4—C121.2079 (18)C7—H7A0.9700
N2—C31.4749 (17)C7—H7B0.9700
N2—C111.5030 (18)C9—C101.519 (2)
N2—C71.5031 (18)C9—H90.9800
N2—H2A1.01 (2)C10—C111.515 (2)
O3—C121.3240 (18)C10—H10A0.9700
O3—H30.8200C10—H10B0.9700
N1—C31.3200 (18)C2—C61.386 (2)
N1—C41.342 (2)C2—C11.514 (2)
O2—C11.2593 (18)C11—H11A0.9700
C3—C21.3897 (19)C11—H11B0.9700
C8—C71.518 (2)C5—C61.376 (2)
C8—C91.528 (2)C5—C41.377 (2)
C8—H8A0.9700C5—H50.9300
C8—H8B0.9700C6—H60.9300
C12—C91.5142 (19)C4—H40.9300
O1—C11.2462 (18)
C3—N2—C11112.86 (11)C10—C9—H9106.9
C3—N2—C7110.53 (11)C8—C9—H9106.9
C11—N2—C7111.03 (11)C11—C10—C9111.73 (12)
C3—N2—H2A103.8 (11)C11—C10—H10A109.3
C11—N2—H2A113.0 (11)C9—C10—H10A109.3
C7—N2—H2A105.2 (11)C11—C10—H10B109.3
C12—O3—H3109.5C9—C10—H10B109.3
C3—N1—C4116.38 (13)H10A—C10—H10B107.9
N1—C3—C2125.81 (13)C6—C2—C3115.73 (13)
N1—C3—N2115.57 (12)C6—C2—C1120.38 (12)
C2—C3—N2118.61 (12)C3—C2—C1123.88 (13)
C7—C8—C9110.46 (12)N2—C11—C10111.12 (12)
C7—C8—H8A109.6N2—C11—H11A109.4
C9—C8—H8A109.6C10—C11—H11A109.4
C7—C8—H8B109.6N2—C11—H11B109.4
C9—C8—H8B109.6C10—C11—H11B109.4
H8A—C8—H8B108.1H11A—C11—H11B108.0
O4—C12—O3123.91 (14)O1—C1—O2126.68 (14)
O4—C12—C9123.86 (13)O1—C1—C2115.64 (13)
O3—C12—C9112.14 (12)O2—C1—C2117.68 (12)
N2—C7—C8110.12 (12)C6—C5—C4118.46 (14)
N2—C7—H7A109.6C6—C5—H5120.8
C8—C7—H7A109.6C4—C5—H5120.8
N2—C7—H7B109.6C5—C6—C2120.24 (14)
C8—C7—H7B109.6C5—C6—H6119.9
H7A—C7—H7B108.1C2—C6—H6119.9
C12—C9—C10112.48 (11)N1—C4—C5123.25 (14)
C12—C9—C8113.54 (12)N1—C4—H4118.4
C10—C9—C8109.78 (11)C5—C4—H4118.4
C12—C9—H9106.9
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.821.772.566 (2)166
N2—H2A···O21.01 (2)1.71 (2)2.599 (2)146.0 (16)
Symmetry code: (i) x, y1/2, z+3/2.

Experimental details

Crystal data
Chemical formulaC12H14N2O4
Mr250.25
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)7.1094 (14), 18.667 (4), 8.6603 (17)
β (°) 93.57 (3)
V3)1147.1 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.20 × 0.20 × 0.20
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2001)
Tmin, Tmax0.964, 0.983
No. of measured, independent and
observed [I > 2σ(I)] reflections
6010, 2237, 1841
Rint0.022
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.118, 1.09
No. of reflections2237
No. of parameters168
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
O3—H3···O1i0.821.772.566 (2)166
N2—H2A···O21.01 (2)1.71 (2)2.599 (2)146.0 (16)
Symmetry code: (i) x, y1/2, 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

First citationBonnet, V., Mongin, F., Trécourt, F., Quéguiner, G. & Knochel, P. (2002). Tetrahedron, 58, 4429–4438.  Web of Science CrossRef CAS Google Scholar
First citationBruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationLéost, F., Chantegrel, B. & Deshayes, C. (1997). Tetrahedron, 53, 7557–7576.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationShreder, K. R., Cajica, J., Du, L., Fraser, A., Hu, Y. & Kohno, Y. (2009). Bioorg. Med. Chem. Lett. 19, 4743–4746.  Web of Science CrossRef PubMed CAS Google Scholar

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