3,5-Bis(ethoxy-carbon-yl)-2,6-dimethyl-1,4-dihydro-pyridine-4-carboxylic acid.

The title mol-ecule, C(14)H(19)NO(6), was synthesized by the reaction of glyoxylic acid, ethyl acetoacetate and NH(4)HCO(3). In the crystal structure, the dihydro-pyridine ring adopts an asymmetric boat-type conformation with the C atom bearing the carboxyl group showing a signficantly larger deviation [0.325 (2) Å] from the base plane then the N atom [0.137 (2) Å]. One of the ethyl groups is disordered over two positions with occupancies of 0.741 (10) and 0.259 (10). The crystal is stabilized by strong inter-molecular hydrogen bonds. N-H⋯O inter-actions form infinite chains in the a direction. O-H⋯O hydrogen bonds form typical carboxylic acid dimers, which link the N-H⋯O chains into a ladder-type double chain.

Related literature

For the electrophysiological activity of 1,4-dipyridine derivatives, see: Fleckenstein (1977 ▶); Cutshall et al. (2002 ▶). For their biological activity, see: Triggle et al. (1980 ▶); Fossheim et al. (1982 ▶); Heinrich et al. (2004 ▶); Henry (2004 ▶).

Experimental

Crystal data

C14H19NO6

M = 297.30

Triclinic,

a = 7.445 (4) Å

b = 9.864 (5) Å

c = 11.908 (2) Å

α = 104.10 (3)°

β = 97.808 (9)°

γ = 111.658 (10)°

V = 763.2 (6) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 291 K

0.36 × 0.30 × 0.28 mm

Data collection

Rigaku SCXmini diffractometer

Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ▶) T min = 0.960, T max = 0.970

6950 measured reflections

2969 independent reflections

2241 reflections with I > 2σ(I)

R int = 0.029

Refinement

R[F 2 > 2σ(F 2)] = 0.063

wR(F 2) = 0.197

S = 1.08

2969 reflections

199 parameters

2 restraints

H-atom parameters constrained

Δρmax = 0.29 e Å−3

Δρmin = −0.24 e Å−3

Data collection: CrystalClear (Rigaku, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; 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: SHELXTL.

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536809024945/kj2129sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809024945/kj2129Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C14H19NO6	Z = 2
Mr = 297.30	F(000) = 316
Triclinic, P1	Dx = 1.294 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.445 (4) Å	Cell parameters from 2034 reflections
b = 9.864 (5) Å	θ = 2.3–27.5°
c = 11.908 (2) Å	µ = 0.10 mm−1
α = 104.10 (3)°	T = 291 K
β = 97.808 (9)°	Block, colourless
γ = 111.658 (10)°	0.36 × 0.30 × 0.28 mm
V = 763.2 (6) Å3

Rigaku SCXmini diffractometer	2969 independent reflections
Radiation source: fine-focus sealed tube	2241 reflections with I > 2σ(I)
graphite	Rint = 0.029
Detector resolution: 13.6612 pixels mm-1	θmax = 26.0°, θmin = 3.0°
ω scans	h = −9→9
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	k = −12→12
Tmin = 0.960, Tmax = 0.970	l = −14→14
6950 measured reflections

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)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.197	H-atom parameters constrained
S = 1.08	w = 1/[σ2(Fo2) + (0.115P)2 + 0.1066P] where P = (Fo2 + 2Fc2)/3
2969 reflections	(Δ/σ)max < 0.001
199 parameters	Δρmax = 0.29 e Å−3
2 restraints	Δρmin = −0.24 e Å−3

Experimental. 1H NMR (DMSO-d6, p.p.m.): δ 1.17 (t, J = 7.0 Hz, 6H, CH2CH3), 2.21 (s, 6H, Me), 4.07 (m, J = 7.0 Hz, 4H, CH2CH3), 4.58 (s, 1H, CH), 8.84 (s, 1H, NH), 11.89 (S, 1H, OH). 13 C NMR (DMSO-d6, p.p.m.): δ 14.72 (CH2CH3), 18.39 (CH3), 39.71 (CH in dihydropyridine ring), 59.55 (CH2), 97.68, 146.27 (quaternary C in dihydropyridine ring), 167.33 (CO), 175.02 (COOH).

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.5752 (3)	0.3833 (2)	0.24556 (18)	0.0403 (5)
H1A	0.4891	0.4029	0.2968	0.048*
C2	0.5338 (3)	0.4308 (2)	0.13568 (18)	0.0418 (5)
C3	0.7927 (3)	0.4825 (2)	0.31506 (19)	0.0471 (5)
C4	0.9329 (3)	0.4276 (3)	0.29898 (19)	0.0482 (5)
C5	0.6783 (3)	0.1670 (2)	0.19748 (19)	0.0447 (5)
C6	0.5295 (3)	0.2141 (2)	0.21075 (17)	0.0403 (5)
C7	1.1547 (3)	0.5129 (3)	0.3518 (3)	0.0700 (7)
H7A	1.1858	0.6168	0.3980	0.105*
H7B	1.2223	0.5136	0.2887	0.105*
H7C	1.1974	0.4627	0.4026	0.105*
C8	0.8460 (4)	0.6388 (3)	0.3946 (2)	0.0691 (7)
C9	0.7022 (9)	0.7955 (6)	0.5064 (4)	0.0796 (16)	0.742 (10)
H9A	0.8340	0.8514	0.5609	0.096*	0.742 (10)
H9B	0.6041	0.7752	0.5532	0.096*	0.742 (10)
C10	0.6670 (9)	0.8858 (5)	0.4323 (6)	0.109 (2)	0.742 (10)
H10D	0.6721	0.9802	0.4824	0.164*	0.742 (10)
H10E	0.5379	0.8281	0.3771	0.164*	0.742 (10)
H10F	0.7678	0.9085	0.3887	0.164*	0.742 (10)
C11	0.6588 (4)	0.0046 (3)	0.1497 (3)	0.0639 (7)
H11A	0.5206	−0.0659	0.1283	0.096*
H11B	0.7320	−0.0178	0.2100	0.096*
H11C	0.7114	−0.0059	0.0804	0.096*
C12	0.3169 (3)	0.1123 (2)	0.18269 (19)	0.0439 (5)
C13	0.0631 (4)	−0.1451 (3)	0.1230 (3)	0.0734 (8)
H13A	−0.0118	−0.1280	0.0588	0.088*
H13B	0.0062	−0.1315	0.1913	0.088*
C14	0.0555 (5)	−0.3023 (3)	0.0839 (4)	0.0916 (11)
H14A	−0.0808	−0.3768	0.0618	0.137*
H14B	0.1301	−0.3177	0.1482	0.137*
H14C	0.1121	−0.3142	0.0164	0.137*
C9'	0.7854 (18)	0.8432 (14)	0.4818 (12)	0.065 (4)*	0.258 (10)
H9'A	0.8895	0.8831	0.5551	0.078*	0.258 (10)
H9'B	0.8364	0.8910	0.4238	0.078*	0.258 (10)
C10'	0.5997 (16)	0.8597 (14)	0.5033 (11)	0.070 (4)*	0.258 (10)
H10A	0.6312	0.9662	0.5417	0.105*	0.258 (10)
H10B	0.5459	0.8009	0.5538	0.105*	0.258 (10)
H10C	0.5030	0.8227	0.4283	0.105*	0.258 (10)
N1	0.8729 (2)	0.2761 (2)	0.23053 (18)	0.0502 (5)
H1D	0.9620	0.2484	0.2073	0.060*
O1	0.5162 (3)	0.35326 (19)	0.03480 (14)	0.0690 (5)
O2	0.5283 (3)	0.56518 (19)	0.15897 (15)	0.0760 (6)
H2A	0.5144	0.5865	0.0969	0.114*
O3	1.0104 (4)	0.7427 (3)	0.4291 (3)	0.1314 (12)
O4	0.6867 (3)	0.6538 (2)	0.42828 (16)	0.0787 (6)
O5	0.1878 (2)	0.16074 (18)	0.18443 (16)	0.0603 (5)
O6	0.2733 (2)	−0.03741 (17)	0.15535 (18)	0.0639 (5)

	U11	U22	U33	U12	U13	U23
C1	0.0385 (10)	0.0393 (10)	0.0487 (11)	0.0212 (8)	0.0147 (8)	0.0137 (8)
C2	0.0404 (10)	0.0340 (10)	0.0518 (12)	0.0200 (8)	0.0104 (8)	0.0091 (9)
C3	0.0447 (11)	0.0448 (11)	0.0502 (12)	0.0201 (9)	0.0089 (9)	0.0117 (9)
C4	0.0402 (11)	0.0529 (12)	0.0527 (12)	0.0210 (9)	0.0110 (9)	0.0169 (10)
C5	0.0443 (11)	0.0453 (11)	0.0554 (12)	0.0265 (9)	0.0186 (9)	0.0191 (9)
C6	0.0391 (10)	0.0404 (10)	0.0485 (11)	0.0221 (9)	0.0143 (8)	0.0159 (9)
C7	0.0421 (12)	0.0737 (17)	0.0839 (18)	0.0226 (12)	0.0055 (11)	0.0162 (14)
C8	0.0668 (16)	0.0540 (14)	0.0696 (16)	0.0268 (13)	−0.0015 (12)	−0.0009 (12)
C9	0.102 (4)	0.070 (3)	0.062 (2)	0.047 (3)	0.017 (2)	−0.004 (2)
C10	0.120 (4)	0.052 (2)	0.130 (5)	0.029 (3)	0.012 (4)	0.007 (3)
C11	0.0567 (14)	0.0494 (13)	0.0981 (19)	0.0345 (12)	0.0273 (13)	0.0212 (13)
C12	0.0423 (11)	0.0406 (11)	0.0555 (12)	0.0228 (9)	0.0169 (9)	0.0160 (9)
C13	0.0475 (13)	0.0486 (14)	0.124 (2)	0.0173 (11)	0.0306 (14)	0.0259 (15)
C14	0.0775 (19)	0.0460 (14)	0.148 (3)	0.0191 (14)	0.043 (2)	0.0279 (17)
N1	0.0374 (9)	0.0496 (10)	0.0691 (12)	0.0240 (8)	0.0191 (8)	0.0161 (9)
O1	0.1177 (15)	0.0498 (9)	0.0501 (10)	0.0486 (10)	0.0179 (9)	0.0143 (8)
O2	0.1359 (18)	0.0542 (10)	0.0573 (10)	0.0630 (12)	0.0200 (10)	0.0166 (8)
O3	0.0760 (15)	0.0632 (14)	0.184 (3)	0.0120 (12)	−0.0075 (16)	−0.0318 (16)
O4	0.0949 (14)	0.0754 (13)	0.0623 (11)	0.0545 (11)	0.0071 (10)	−0.0064 (9)
O5	0.0400 (8)	0.0500 (9)	0.0941 (13)	0.0261 (7)	0.0178 (8)	0.0163 (8)
O6	0.0432 (8)	0.0396 (8)	0.1140 (14)	0.0194 (7)	0.0259 (9)	0.0266 (9)

C1—C6	1.510 (3)	C10—H10E	0.9600
C1—C2	1.524 (3)	C10—H10F	0.9600
C1—C3	1.528 (3)	C11—H11A	0.9600
C1—H1A	0.9800	C11—H11B	0.9600
C2—O1	1.217 (3)	C11—H11C	0.9600
C2—O2	1.304 (2)	C12—O5	1.222 (2)
C3—C4	1.357 (3)	C12—O6	1.332 (2)
C3—C8	1.472 (3)	C13—O6	1.462 (3)
C4—N1	1.383 (3)	C13—C14	1.483 (4)
C4—C7	1.505 (3)	C13—H13A	0.9700
C5—C6	1.363 (3)	C13—H13B	0.9700
C5—N1	1.378 (3)	C14—H14A	0.9600
C5—C11	1.508 (3)	C14—H14B	0.9600
C6—C12	1.465 (3)	C14—H14C	0.9600
C7—H7A	0.9600	C9'—C10'	1.499 (15)
C7—H7B	0.9600	C9'—O4	1.649 (12)
C7—H7C	0.9600	C9'—H9'A	0.9700
C8—O3	1.204 (3)	C9'—H9'B	0.9700
C8—O4	1.348 (3)	C10'—H10A	0.9600
C9—O4	1.432 (4)	C10'—H10B	0.9600
C9—C10	1.461 (8)	C10'—H10C	0.9600
C9—H9A	0.9700	N1—H1D	0.8600
C9—H9B	0.9700	O2—H2A	0.8200
C10—H10D	0.9600
C6—C1—C2	111.10 (16)	H10E—C10—H10F	109.5
C6—C1—C3	111.42 (16)	C5—C11—H11A	109.5
C2—C1—C3	108.83 (16)	C5—C11—H11B	109.5
C6—C1—H1A	108.5	H11A—C11—H11B	109.5
C2—C1—H1A	108.5	C5—C11—H11C	109.5
C3—C1—H1A	108.5	H11A—C11—H11C	109.5
O1—C2—O2	122.4 (2)	H11B—C11—H11C	109.5
O1—C2—C1	122.99 (17)	O5—C12—O6	122.05 (19)
O2—C2—C1	114.51 (17)	O5—C12—C6	122.53 (19)
C4—C3—C8	121.5 (2)	O6—C12—C6	115.42 (17)
C4—C3—C1	119.72 (19)	O6—C13—C14	106.9 (2)
C8—C3—C1	118.72 (19)	O6—C13—H13A	110.3
C3—C4—N1	119.07 (18)	C14—C13—H13A	110.3
C3—C4—C7	127.0 (2)	O6—C13—H13B	110.3
N1—C4—C7	113.86 (19)	C14—C13—H13B	110.3
C6—C5—N1	118.93 (18)	H13A—C13—H13B	108.6
C6—C5—C11	127.8 (2)	C13—C14—H14A	109.5
N1—C5—C11	113.28 (17)	C13—C14—H14B	109.5
C5—C6—C12	125.35 (19)	H14A—C14—H14B	109.5
C5—C6—C1	120.07 (18)	C13—C14—H14C	109.5
C12—C6—C1	114.31 (16)	H14A—C14—H14C	109.5
C4—C7—H7A	109.5	H14B—C14—H14C	109.5
C4—C7—H7B	109.5	C10'—C9'—O4	97.3 (9)
H7A—C7—H7B	109.5	C10'—C9'—H9'A	112.3
C4—C7—H7C	109.5	O4—C9'—H9'A	112.3
H7A—C7—H7C	109.5	C10'—C9'—H9'B	112.3
H7B—C7—H7C	109.5	O4—C9'—H9'B	112.3
O3—C8—O4	122.4 (3)	H9'A—C9'—H9'B	109.9
O3—C8—C3	125.8 (3)	C9'—C10'—H10A	109.5
O4—C8—C3	111.8 (2)	C9'—C10'—H10B	109.5
O4—C9—C10	107.7 (4)	H10A—C10'—H10B	109.5
O4—C9—H9A	110.2	C9'—C10'—H10C	109.5
C10—C9—H9A	110.2	H10A—C10'—H10C	109.5
O4—C9—H9B	110.2	H10B—C10'—H10C	109.5
C10—C9—H9B	110.2	C5—N1—C4	123.75 (16)
H9A—C9—H9B	108.5	C5—N1—H1D	118.1
C9—C10—H10D	109.5	C4—N1—H1D	118.1
C9—C10—H10E	109.5	C2—O2—H2A	109.5
H10D—C10—H10E	109.5	C8—O4—C9	121.9 (3)
C9—C10—H10F	109.5	C8—O4—C9'	97.6 (5)
H10D—C10—H10F	109.5	C12—O6—C13	117.96 (17)
C6—C1—C2—O1	−17.2 (3)	C1—C3—C8—O3	−158.8 (3)
C3—C1—C2—O1	105.9 (2)	C4—C3—C8—O4	−160.1 (2)
C6—C1—C2—O2	166.01 (18)	C1—C3—C8—O4	22.5 (3)
C3—C1—C2—O2	−70.9 (2)	C5—C6—C12—O5	−172.2 (2)
C6—C1—C3—C4	25.8 (3)	C1—C6—C12—O5	1.8 (3)
C2—C1—C3—C4	−97.1 (2)	C5—C6—C12—O6	8.0 (3)
C6—C1—C3—C8	−156.7 (2)	C1—C6—C12—O6	−177.98 (17)
C2—C1—C3—C8	80.4 (2)	C6—C5—N1—C4	13.9 (3)
C8—C3—C4—N1	175.1 (2)	C11—C5—N1—C4	−166.0 (2)
C1—C3—C4—N1	−7.5 (3)	C3—C4—N1—C5	−14.1 (3)
C8—C3—C4—C7	−2.6 (4)	C7—C4—N1—C5	163.9 (2)
C1—C3—C4—C7	174.8 (2)	O3—C8—O4—C9	0.8 (5)
N1—C5—C6—C12	−178.35 (18)	C3—C8—O4—C9	179.6 (3)
C11—C5—C6—C12	1.5 (4)	O3—C8—O4—C9'	15.3 (6)
N1—C5—C6—C1	8.0 (3)	C3—C8—O4—C9'	−165.9 (5)
C11—C5—C6—C1	−172.2 (2)	C10—C9—O4—C8	89.7 (5)
C2—C1—C6—C5	95.5 (2)	C10'—C9'—O4—C8	172.6 (8)
C3—C1—C6—C5	−26.0 (3)	O5—C12—O6—C13	2.0 (3)
C2—C1—C6—C12	−78.8 (2)	C6—C12—O6—C13	−178.2 (2)
C3—C1—C6—C12	159.62 (17)	C14—C13—O6—C12	173.7 (2)
C4—C3—C8—O3	18.6 (5)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1D···O5i	0.86	2.17	3.018 (2)	167
O2—H2A···O1ii	0.82	1.82	2.641 (2)	176

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1D⋯O5i	0.86	2.17	3.018 (2)	167
O2—H2A⋯O1ii	0.82	1.82	2.641 (2)	176

Symmetry codes: (i) ; (ii) .