Ethyl 4-hydroxy­methyl-2-methyl­pyridine-5-carboxyl­ate

Abstract

The title compound, C₁₀H₁₃NO₃, was obtained as a by-product of the aldolization reaction of furo[3,4-c]pyridin-3(1H)-one with thio­phene-2-carboxaldehyde. The substituents on the pyridine ring are nearly coplanar, with an 8.1 (2)° rotation of the hydroxmethyl group from this plane. The mol­ecules assemble in the crystal structure as chains via O—H⋯N hydrogen bonding between the pyridine N atom and a neighbouring hydroxy­methyl OH group.

Related literature

For related literature, see: Goswami et al. (2006 ▶), Wu et al. (2006 ▶). For bond-length data, see: Allen et al., (1987 ▶).

Experimental

Crystal data

• C₁₀H₁₃NO₃

• M _r = 195.21

• Monoclinic,

• a = 4.4998 (2) Å

• b = 15.4499 (8) Å

• c = 14.2036 (7) Å

• β = 96.417 (1)°

• V = 981.27 (8) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 87 (2) K

• 0.32 × 0.18 × 0.12 mm

Data collection

• Siemens SMART CCD diffractometer

• Absorption correction: none

• 5759 measured reflections

• 1987 independent reflections

• 1786 reflections with I > 2σ(I)

• R _int = 0.081

Refinement

• R[F ² > 2σ(F ²)] = 0.049

• wR(F ²) = 0.134

• S = 1.02

• 1987 reflections

• 130 parameters

• H-atom parameters constrained

• Δρ_max = 0.30 e Å⁻³

• Δρ_min = −0.28 e Å⁻³

Data collection: SMART (Siemens, 1995 ▶); cell refinement: SAINT (Siemens, 1995 ▶); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯N1i	0.82	2.01	2.8227 (17)	170

Symmetry code: (i) .

supplementary crystallographic information

Comment

The molecular structure of the title compound is shown in Fig. 1. The bond lengths and angles are normal (Allen et al., 1987). The ethyl ester group is nearly coplanar with the pyridine ring (C1-C5,N1 rmsd 0.0064 Å; C2,C8,C9,C10,O1,O2 rmsd 0.0064 Å, interplanar angle 2.17 (9)°). The hydroxymethyl group is rotated slightly out of the plane (O3—C7—C3—C4 8.1 (2)°).

The molecules in the crystal are connected via hydrogen bonding between the pyridine N atom and an adjacent OH group (Table 1) to give chains along the c axis (Figure 2a). These chains are stacked along the a axis (Figure 2 b). Similar hydrogen bonding interactions are observed in other hydroxymethyl substituted pyridines (Goswami et al., 2006, Wu et al., 2006).

Experimental

The title compound was obtained as a by-product of the aldolization reaction of furo[3,4-c]pyridin-3(1H)-one with thiophene-2-carboxaldehyde. The desired product was not isolated, only the starting material and the title compound were characterized after the reaction.

Ethyl 4-(hydroxymethyl)-6-methylnicotinate (I): Furo[3,4-c]pyridin-3(1H)-one (II) (110 mg,0.74 mmol, 1 eq.) was suspended in EtOH (15 ml) at 65°C. Thiophene-2-carboxaldehyde (III) (99 mg, 0.88 mmol) and triethylamine (18 mg,0.18 mmol) were then added and the reaction mixture stirred at 80°C for 6 days. After cooling to room temperature the reaction was quenched with 1M HCl and extracted with EtOAc. The organic layer was rinsed with water and dried over MgSO4. Removal of MgSO₄ by filtration and evaporation of solvent under reduced pressure gave the crude product. This product was dissolved in dichloromethane and stored at 4°C to yield colorless crystals (25 mg, 17% yield) which were isolated by filtration and identified as the title compound. ¹H NMR (400 MHz, CD₃)₂SO, 298 K) δ 8.83 (s, 1 H), 7.03 (s, 1 H), 5.43 (s, 1 H), 4.83 (br s, 2 H), 4.30 (q, J = 7.1 Hz, 2 H), 2.54 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3 H). LCMS (APCI⁺) calcd for C₁₀H₁₃NO₃ 195 (MH⁺), found 196.

Refinement

Hydrogen atoms were placed in calculated positions and refined using the riding model [O—H 0.82 Å, C—H 0.93–0.97 Å), with U_iso(H) = 1.5 times U_eq(O) and U_iso(H) = 1.2 or 1.5 times U_eq(C).

Figures

Fig. 1.

Structure of (I) showing 50% probability displacement ellipsoids for non-hydrogen atoms and hydrogen atoms as arbitary spheres.

Fig. 2.

Illustration of the arrangement of the complex (I) in the crystal along the a axis showing pyridine N···H—O hydrogen bonding arrangement.

Fig. 3.

Illustration of the arrangement of the complex (I) in the crystal along the a axis showing stacking of hydrogen bonded chains.

Crystal data

C10H13NO3	F(000) = 416
Mr = 195.21	Dx = 1.321 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 4.4998 (2) Å	Cell parameters from 4149 reflections
b = 15.4499 (8) Å	θ = 2.0–26.3°
c = 14.2036 (7) Å	µ = 0.10 mm−1
β = 96.417 (1)°	T = 87 K
V = 981.27 (8) Å3	Needle, colourless
Z = 4	0.32 × 0.18 × 0.12 mm

Data collection

Siemens SMART CCD diffractometer	1786 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.081
graphite	θmax = 26.3°, θmin = 2.0°
Area–detector ω scans	h = −5→5
5759 measured reflections	k = −19→17
1987 independent reflections	l = −17→12

Refinement

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.134	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0608P)2 + 0.7105P] where P = (Fo2 + 2Fc2)/3
1987 reflections	(Δ/σ)max < 0.001
130 parameters	Δρmax = 0.30 e Å−3
0 restraints	Δρmin = −0.28 e Å−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.4226 (3)	0.73560 (9)	0.54034 (9)	0.0197 (3)
O1	0.7485 (3)	0.96228 (7)	0.64708 (8)	0.0207 (3)
O2	0.5468 (3)	0.95300 (8)	0.78490 (8)	0.0255 (3)
O3	−0.0290 (3)	0.75164 (8)	0.84444 (8)	0.0215 (3)
H3	−0.0566	0.7606	0.8997	0.032*
C1	0.5219 (4)	0.81023 (11)	0.58079 (11)	0.0184 (4)
H1	0.6416	0.8453	0.5474	0.022*
C2	0.4576 (3)	0.83885 (10)	0.66979 (11)	0.0167 (3)
C3	0.2720 (3)	0.78652 (11)	0.72042 (10)	0.0167 (3)
C4	0.1707 (4)	0.70920 (11)	0.67810 (11)	0.0189 (4)
H4	0.0480	0.6732	0.7092	0.023*
C5	0.2507 (4)	0.68475 (11)	0.58930 (11)	0.0191 (4)
C6	0.1465 (5)	0.60006 (12)	0.54492 (12)	0.0290 (4)
H6A	−0.0682	0.5987	0.5366	0.044*
H6B	0.2204	0.5532	0.5854	0.044*
H6C	0.2206	0.5942	0.4844	0.044*
C7	0.1868 (4)	0.81091 (11)	0.81720 (11)	0.0184 (4)
H7A	0.3629	0.8099	0.8633	0.022*
H7B	0.1053	0.8691	0.8152	0.022*
C8	0.5846 (3)	0.92273 (11)	0.70790 (11)	0.0184 (4)
C9	0.8760 (4)	1.04629 (11)	0.67761 (12)	0.0218 (4)
H9A	1.0137	1.0397	0.7348	0.026*
H9B	0.7187	1.0860	0.6906	0.026*
C10	1.0378 (4)	1.08024 (12)	0.59824 (12)	0.0242 (4)
H10A	1.1936	1.0406	0.5864	0.036*
H10B	1.1235	1.1357	0.6156	0.036*
H10C	0.8994	1.0861	0.5421	0.036*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
N1	0.0253 (7)	0.0210 (7)	0.0131 (6)	0.0006 (5)	0.0027 (5)	0.0001 (5)
O1	0.0250 (6)	0.0200 (6)	0.0180 (6)	−0.0041 (5)	0.0057 (5)	−0.0031 (5)
O2	0.0332 (7)	0.0261 (7)	0.0180 (6)	−0.0048 (5)	0.0073 (5)	−0.0061 (5)
O3	0.0263 (6)	0.0275 (6)	0.0115 (5)	−0.0033 (5)	0.0060 (5)	−0.0002 (5)
C1	0.0216 (8)	0.0205 (8)	0.0137 (7)	−0.0002 (6)	0.0043 (6)	0.0020 (6)
C2	0.0169 (7)	0.0200 (8)	0.0127 (7)	0.0034 (6)	0.0001 (6)	0.0000 (6)
C3	0.0174 (7)	0.0216 (8)	0.0108 (7)	0.0038 (6)	0.0005 (6)	0.0028 (6)
C4	0.0223 (8)	0.0220 (8)	0.0123 (7)	−0.0013 (6)	0.0022 (6)	0.0032 (6)
C5	0.0237 (8)	0.0206 (8)	0.0127 (7)	0.0007 (6)	0.0005 (6)	0.0001 (6)
C6	0.0450 (11)	0.0257 (9)	0.0170 (8)	−0.0089 (8)	0.0062 (7)	−0.0030 (7)
C7	0.0215 (8)	0.0218 (8)	0.0123 (7)	−0.0003 (6)	0.0032 (6)	0.0003 (6)
C8	0.0191 (7)	0.0210 (8)	0.0151 (7)	0.0024 (6)	0.0021 (6)	0.0006 (6)
C9	0.0255 (8)	0.0184 (8)	0.0217 (8)	−0.0018 (6)	0.0026 (7)	−0.0035 (6)
C10	0.0270 (8)	0.0234 (9)	0.0219 (8)	−0.0051 (7)	0.0015 (7)	−0.0014 (7)

Geometric parameters (Å, °)

N1—C1	1.342 (2)	C4—H4	0.9300
N1—C5	1.349 (2)	C5—C6	1.504 (2)
O1—C8	1.344 (2)	C6—H6A	0.9600
O1—C9	1.4649 (19)	C6—H6B	0.9600
O2—C8	1.219 (2)	C6—H6C	0.9600
O3—C7	1.420 (2)	C7—H7A	0.9700
O3—H3	0.8200	C7—H7B	0.9700
C1—C2	1.400 (2)	C9—C10	1.503 (2)
C1—H1	0.9300	C9—H9A	0.9700
C2—C3	1.415 (2)	C9—H9B	0.9700
C2—C8	1.493 (2)	C10—H10A	0.9600
C3—C4	1.391 (2)	C10—H10B	0.9600
C3—C7	1.515 (2)	C10—H10C	0.9600
C4—C5	1.402 (2)
C1—N1—C5	117.54 (14)	H6B—C6—H6C	109.5
C8—O1—C9	115.95 (13)	O3—C7—C3	109.70 (13)
C7—O3—H3	109.5	O3—C7—H7A	109.7
N1—C1—C2	124.43 (15)	C3—C7—H7A	109.7
N1—C1—H1	117.8	O3—C7—H7B	109.7
C2—C1—H1	117.8	C3—C7—H7B	109.7
C1—C2—C3	118.16 (15)	H7A—C7—H7B	108.2
C1—C2—C8	119.48 (14)	O2—C8—O1	122.94 (15)
C3—C2—C8	122.36 (14)	O2—C8—C2	124.91 (15)
C4—C3—C2	117.04 (14)	O1—C8—C2	112.14 (13)
C4—C3—C7	120.10 (14)	O1—C9—C10	107.08 (13)
C2—C3—C7	122.86 (14)	O1—C9—H9A	110.3
C3—C4—C5	121.03 (15)	C10—C9—H9A	110.3
C3—C4—H4	119.5	O1—C9—H9B	110.3
C5—C4—H4	119.5	C10—C9—H9B	110.3
N1—C5—C4	121.78 (15)	H9A—C9—H9B	108.6
N1—C5—C6	117.43 (14)	C9—C10—H10A	109.5
C4—C5—C6	120.79 (15)	C9—C10—H10B	109.5
C5—C6—H6A	109.5	H10A—C10—H10B	109.5
C5—C6—H6B	109.5	C9—C10—H10C	109.5
H6A—C6—H6B	109.5	H10A—C10—H10C	109.5
C5—C6—H6C	109.5	H10B—C10—H10C	109.5
H6A—C6—H6C	109.5
C5—N1—C1—C2	−0.4 (2)	C3—C4—C5—N1	−1.5 (2)
N1—C1—C2—C3	−0.9 (2)	C3—C4—C5—C6	178.53 (15)
N1—C1—C2—C8	179.21 (14)	C4—C3—C7—O3	−8.1 (2)
C1—C2—C3—C4	1.0 (2)	C2—C3—C7—O3	172.83 (13)
C8—C2—C3—C4	−179.12 (14)	C9—O1—C8—O2	−1.5 (2)
C1—C2—C3—C7	−179.91 (14)	C9—O1—C8—C2	178.51 (12)
C8—C2—C3—C7	0.0 (2)	C1—C2—C8—O2	−178.81 (16)
C2—C3—C4—C5	0.1 (2)	C3—C2—C8—O2	1.3 (2)
C7—C3—C4—C5	−178.98 (14)	C1—C2—C8—O1	1.2 (2)
C1—N1—C5—C4	1.6 (2)	C3—C2—C8—O1	−178.66 (13)
C1—N1—C5—C6	−178.42 (15)	C8—O1—C9—C10	−177.70 (13)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1i	0.82	2.01	2.8227 (17)	170.

Symmetry codes: (i) x−1/2, −y+3/2, z+1/2.