2-(Benzyl­carbamo­yl)nicotinic acid

Mao, Y.-C.; Wu, H.; Shan, J.-J.; Yan, K.

doi:10.1107/S1600536813024483

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 10| October 2013| Page o1520

doi:10.1107/S1600536813024483

Open

access

2-(Benzylcarbamoyl)nicotinic acid

Yan-Cao Mao,^a,^b Hao Wu,^a ^* Jin-Jun Shan ^c and Ke Yan ^d

^aCollege of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, People's Republic of China, ^bDepartment of Applied Chemistry, Nanjing College of Chemical Technology, Nanjing 210048, People's Republic of China, ^cMolecular Biology Laboratory of SATCM, First Medicine College, Nanjing University of Chinese Medicine, Nanjing 210023, People's Republic of China, and ^dScience and Technology Department, Nanjing University of Chinese Medicine, Nanjing 210023, People's Republic of China
^*Correspondence e-mail: wuhaomrs@163.com

(Received 19 July 2013; accepted 2 September 2013; online 7 September 2013)

In the title compound, C₁₄H₁₂N₂O₃, the pyridine ring is twisted with respect to the phenyl ring and the carboxylic acid group at angles of 37.1 (5) and 8.1 (3)°, respectively; the phenyl ring forms a dihedral angle of 41.4 (1)° with the mean plane of the C—NH—C=O fragment. An intramolecular O—H⋯O hydrogen bond occurs between the carboxylic acid and carbonyl groups. In the crystal, N—H⋯O hydrogen bonds link molecules into a supramolecular chain running along the a-axis direction.

Related literature

For background to the title compound, see: Konshin et al. (2010 ). For a related structure, see: Koch et al. (2008 ).

Experimental

Crystal data

C₁₄H₁₂N₂O₃
M_r = 256.26
Orthorhombic, P b c a
a = 13.024 (3) Å
b = 8.4110 (17) Å
c = 23.143 (5) Å
V = 2535.2 (9) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
4586 measured reflections
2326 independent reflections
1242 reflections with I > 2σ(I)
R_int = 0.096
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.057
wR(F²) = 0.167
S = 1.00
2326 reflections
172 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O3ⁱ	0.86	2.24	3.033 (3)	154
O3—H3B⋯O1	0.82	1.62	2.435 (3)	179
Symmetry code: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ .

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995 ); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536813024483/xu5724sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813024483/xu5724Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813024483/xu5724Isup3.cml

checkCIF report

Comment top

Drugs that reduce blood coagulation and are widely used for therapy and prevention in surgical operations and for ischemic heart disease and other diseases are known to have several serious shortcomings (Konshin et al., 2010). Our research on biologically active amides and hydrazides of pyridinecarboxylic acids led to the synthesis of substituted 3-carboxypicolinic acid amides.

The molecular structure of the title compound is shown in Fig. 1. The pyridine ring is twisted by 37.1 (5) and 8.1 (3)°, with respect to the benzene ring and carboxyl group; the benzene ring forms a dihedral angle of 41.4 (1)° with the mean plane of the C—NH—C═O fragment.

As shown in Figure 2, the molecules are linked by N—H···O hydrogen bonds into chain in the crystal lattice (Table 1).

Related literature top

For background to the title compound, see: Konshin et al. (2010). For a related structure, see: Koch et al. (2008).

Experimental top

A solution of quinolinic acid anhydride (20 mmol) in CHCl₃ (20 ml) was treated with Et₃N (20 mmol). Then a solution of phenylmethanamine (20 mmol) in CHCl₃ (15 ml) was added gradually at a rate such that the temperature of the mixture did not rise above 303 K. The mixture was left for 12 h. The resulting precipitate was filtered off, dissolved in the minimum amount of water, and precipitated by acetic acid. The precipitate was separated, washed with water and recrystallized from EtOH.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo,1995); 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).

Figures top

	Fig. 1. The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids at the 30% probability level.
	Fig. 2. A packing diagram of (I). Intermolecular hydrogen bonds are shown as dashed lines.

2-(Benzylcarbamoyl)pyridine-3-carboxylic acid top

Crystal data top

C₁₄H₁₂N₂O₃	F(000) = 1072
M_r = 256.26	D_x = 1.343 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 13.024 (3) Å	θ = 10–13°
b = 8.4110 (17) Å	µ = 0.10 mm⁻¹
c = 23.143 (5) Å	T = 293 K
V = 2535.2 (9) Å³	Block, colorless
Z = 8	0.30 × 0.20 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.096
Radiation source: fine-focus sealed tube	θ_max = 25.4°, θ_min = 1.8°
Graphite monochromator	h = 0→15
ω/2θ scans	k = 0→10
4586 measured reflections	l = −27→27
2326 independent reflections	3 standard reflections every 200 reflections
1242 reflections with I > 2σ(I)	intensity decay: 1%

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.167	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.053P)²] where P = (F_o² + 2F_c²)/3
2326 reflections	(Δ/σ)_max < 0.001
172 parameters	Δρ_max = 0.22 e Å⁻³
0 restraints	Δρ_min = −0.14 e Å⁻³

Crystal data top

C₁₄H₁₂N₂O₃	V = 2535.2 (9) Å³
M_r = 256.26	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 13.024 (3) Å	µ = 0.10 mm⁻¹
b = 8.4110 (17) Å	T = 293 K
c = 23.143 (5) Å	0.30 × 0.20 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.096
4586 measured reflections	3 standard reflections every 200 reflections
2326 independent reflections	intensity decay: 1%
1242 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.057	0 restraints
wR(F²) = 0.167	H-atom parameters constrained
S = 1.00	Δρ_max = 0.22 e Å⁻³
2326 reflections	Δρ_min = −0.14 e Å⁻³
172 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
N1	0.42068 (17)	0.3451 (3)	0.54279 (10)	0.0496 (7)
H1A	0.4839	0.3212	0.5365	0.060*
O1	0.25706 (15)	0.3073 (3)	0.51797 (9)	0.0653 (7)
C1	0.4634 (3)	0.3853 (5)	0.68730 (14)	0.0751 (11)
H1B	0.5234	0.4402	0.6784	0.090*
N2	0.49338 (17)	0.1694 (3)	0.46226 (10)	0.0514 (7)
O2	0.17921 (17)	−0.0277 (3)	0.38457 (12)	0.0857 (8)
C2	0.4535 (3)	0.3113 (6)	0.74105 (17)	0.0989 (15)
H2B	0.5069	0.3171	0.7677	0.119*
O3	0.15332 (14)	0.1519 (3)	0.45110 (10)	0.0694 (7)
H3B	0.1874	0.2050	0.4738	0.104*
C3	0.3665 (3)	0.2309 (6)	0.75455 (17)	0.0930 (13)
H3A	0.3598	0.1830	0.7906	0.112*
C4	0.2891 (3)	0.2204 (6)	0.71546 (18)	0.0911 (13)
H4A	0.2297	0.1646	0.7249	0.109*
C5	0.2975 (3)	0.2918 (5)	0.66178 (15)	0.0754 (11)
H5A	0.2444	0.2824	0.6351	0.090*
C6	0.3857 (2)	0.3779 (4)	0.64753 (13)	0.0538 (8)
C7	0.3974 (3)	0.4559 (4)	0.58954 (13)	0.0605 (9)
H7A	0.3343	0.5117	0.5803	0.073*
H7B	0.4520	0.5342	0.5918	0.073*
C8	0.3502 (2)	0.2801 (4)	0.50990 (13)	0.0491 (8)
C9	0.3895 (2)	0.1729 (3)	0.46270 (12)	0.0426 (7)
C10	0.3298 (2)	0.0857 (3)	0.42331 (13)	0.0478 (7)
C11	0.3839 (3)	−0.0003 (4)	0.38152 (14)	0.0584 (9)
H11A	0.3478	−0.0579	0.3539	0.070*
C12	0.4897 (3)	−0.0013 (4)	0.38041 (15)	0.0615 (9)
H12A	0.5255	−0.0579	0.3524	0.074*
C13	0.5402 (2)	0.0838 (4)	0.42194 (13)	0.0576 (8)
H13A	0.6116	0.0817	0.4219	0.069*
C14	0.2149 (2)	0.0680 (4)	0.41832 (14)	0.0546 (8)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0415 (13)	0.0663 (17)	0.0410 (14)	0.0020 (13)	0.0024 (11)	−0.0069 (13)
O1	0.0363 (11)	0.1000 (16)	0.0595 (13)	0.0078 (11)	0.0056 (11)	−0.0135 (14)
C1	0.072 (2)	0.103 (3)	0.050 (2)	−0.014 (2)	−0.0011 (18)	−0.019 (2)
N2	0.0376 (12)	0.0689 (17)	0.0478 (15)	0.0004 (12)	0.0062 (11)	−0.0022 (15)
O2	0.0640 (15)	0.1065 (19)	0.0865 (18)	−0.0091 (15)	−0.0183 (14)	−0.0250 (18)
C2	0.097 (3)	0.155 (4)	0.045 (2)	0.000 (3)	−0.010 (2)	−0.016 (3)
O3	0.0432 (12)	0.0951 (18)	0.0701 (15)	0.0013 (12)	−0.0042 (11)	−0.0104 (15)
C3	0.121 (4)	0.115 (3)	0.043 (2)	0.011 (3)	0.014 (2)	0.002 (3)
C4	0.090 (3)	0.111 (3)	0.072 (3)	−0.003 (3)	0.022 (2)	0.017 (3)
C5	0.057 (2)	0.104 (3)	0.065 (2)	0.000 (2)	0.0027 (17)	0.010 (2)
C6	0.0551 (18)	0.063 (2)	0.0434 (18)	0.0046 (16)	0.0044 (15)	−0.0106 (17)
C7	0.061 (2)	0.066 (2)	0.054 (2)	0.0011 (16)	0.0074 (16)	−0.0053 (19)
C8	0.0407 (16)	0.064 (2)	0.0428 (17)	0.0004 (15)	0.0053 (14)	0.0043 (16)
C9	0.0425 (14)	0.0538 (17)	0.0316 (15)	−0.0007 (14)	0.0031 (12)	0.0031 (15)
C10	0.0486 (17)	0.0525 (17)	0.0425 (17)	0.0008 (14)	0.0033 (14)	0.0076 (17)
C11	0.068 (2)	0.069 (2)	0.0390 (17)	0.0004 (18)	0.0001 (16)	−0.0058 (19)
C12	0.064 (2)	0.070 (2)	0.050 (2)	0.0057 (18)	0.0082 (17)	−0.0099 (19)
C13	0.0458 (18)	0.071 (2)	0.0562 (19)	0.0061 (16)	0.0127 (16)	−0.0013 (19)
C14	0.0488 (19)	0.0655 (19)	0.0494 (19)	−0.0037 (17)	−0.0065 (15)	0.0055 (19)

Geometric parameters (Å, º) top

N1—C8	1.312 (3)	C4—C5	1.384 (5)
N1—C7	1.460 (4)	C4—H4A	0.9300
N1—H1A	0.8600	C5—C6	1.398 (5)
O1—C8	1.249 (3)	C5—H5A	0.9300
C1—C6	1.369 (4)	C6—C7	1.502 (4)
C1—C2	1.397 (5)	C7—H7A	0.9700
C1—H1B	0.9300	C7—H7B	0.9700
N2—C13	1.327 (4)	C8—C9	1.506 (4)
N2—C9	1.353 (3)	C9—C10	1.405 (4)
O2—C14	1.214 (4)	C10—C11	1.398 (4)
C2—C3	1.357 (5)	C10—C14	1.508 (4)
C2—H2B	0.9300	C11—C12	1.378 (4)
O3—C14	1.310 (4)	C11—H11A	0.9300
O3—H3B	0.8200	C12—C13	1.367 (4)
C3—C4	1.357 (5)	C12—H12A	0.9300
C3—H3A	0.9300	C13—H13A	0.9300

C8—N1—C7	123.4 (2)	C6—C7—H7A	108.8
C8—N1—H1A	118.3	N1—C7—H7B	108.8
C7—N1—H1A	118.3	C6—C7—H7B	108.8
C6—C1—C2	120.7 (4)	H7A—C7—H7B	107.7
C6—C1—H1B	119.7	O1—C8—N1	121.1 (3)
C2—C1—H1B	119.7	O1—C8—C9	123.3 (3)
C13—N2—C9	118.5 (3)	N1—C8—C9	115.6 (2)
C3—C2—C1	120.3 (4)	N2—C9—C10	122.5 (3)
C3—C2—H2B	119.9	N2—C9—C8	111.0 (2)
C1—C2—H2B	119.9	C10—C9—C8	126.5 (2)
C14—O3—H3B	109.5	C11—C10—C9	116.1 (3)
C2—C3—C4	120.0 (4)	C11—C10—C14	113.3 (3)
C2—C3—H3A	120.0	C9—C10—C14	130.6 (3)
C4—C3—H3A	120.0	C12—C11—C10	121.3 (3)
C3—C4—C5	120.7 (4)	C12—C11—H11A	119.3
C3—C4—H4A	119.6	C10—C11—H11A	119.3
C5—C4—H4A	119.6	C13—C12—C11	117.7 (3)
C4—C5—C6	120.1 (4)	C13—C12—H12A	121.2
C4—C5—H5A	119.9	C11—C12—H12A	121.1
C6—C5—H5A	119.9	N2—C13—C12	123.9 (3)
C1—C6—C5	118.2 (3)	N2—C13—H13A	118.1
C1—C6—C7	120.4 (3)	C12—C13—H13A	118.1
C5—C6—C7	121.4 (3)	O2—C14—O3	119.7 (3)
N1—C7—C6	113.9 (2)	O2—C14—C10	119.6 (3)
N1—C7—H7A	108.8	O3—C14—C10	120.7 (3)

C6—C1—C2—C3	−0.1 (7)	N1—C8—C9—N2	−2.3 (4)
C1—C2—C3—C4	0.9 (7)	O1—C8—C9—C10	−2.5 (5)
C2—C3—C4—C5	−0.4 (7)	N1—C8—C9—C10	177.7 (3)
C3—C4—C5—C6	−1.0 (6)	N2—C9—C10—C11	−2.8 (4)
C2—C1—C6—C5	−1.2 (6)	C8—C9—C10—C11	177.2 (3)
C2—C1—C6—C7	−179.2 (3)	N2—C9—C10—C14	177.0 (3)
C4—C5—C6—C1	1.7 (5)	C8—C9—C10—C14	−3.0 (5)
C4—C5—C6—C7	179.7 (3)	C9—C10—C11—C12	1.5 (4)
C8—N1—C7—C6	93.2 (4)	C14—C10—C11—C12	−178.4 (3)
C1—C6—C7—N1	102.4 (4)	C10—C11—C12—C13	0.5 (5)
C5—C6—C7—N1	−75.5 (4)	C9—N2—C13—C12	0.2 (5)
C7—N1—C8—O1	−1.8 (5)	C11—C12—C13—N2	−1.4 (5)
C7—N1—C8—C9	178.1 (2)	C11—C10—C14—O2	7.7 (4)
C13—N2—C9—C10	2.1 (4)	C9—C10—C14—O2	−172.1 (3)
C13—N2—C9—C8	−178.0 (3)	C11—C10—C14—O3	−174.0 (3)
O1—C8—C9—N2	177.6 (3)	C9—C10—C14—O3	6.2 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3ⁱ	0.86	2.24	3.033 (3)	154
O3—H3B···O1	0.82	1.62	2.435 (3)	179

Symmetry code: (i) x+1/2, −y+1/2, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3ⁱ	0.86	2.24	3.033 (3)	154
O3—H3B···O1	0.82	1.62	2.435 (3)	179

Symmetry code: (i) x+1/2, −y+1/2, −z+1.

Acknowledgements

The authors thank the Center of Testing and Analysis, Nanjing University, for the data collection.

References

Enraf–Nonius (1994). CAD-4 EXPRESS. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
Koch, C., Görls, H. & Westerhausen, M. (2008). Acta Cryst. E64, o2358. Web of Science CSD CrossRef IUCr Journals Google Scholar
Konshin, M. E., Syropyatov, B. Y., Vakhrin, M. I., Neifel'd, P. G., Feshin, V. P., Shurov, S. N. & Odegova1, T. F. (2010). Pharm. Chem. J. 44, 476–479. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar