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

Boyd, P.D.W.; Lena, G.; Spicer, J.A.

doi:10.1107/S160053680801026X

organic compounds

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ISSN: 2056-9890

Volume 64| Part 5| May 2008| Page o883

doi:10.1107/S160053680801026X

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

Peter D. W. Boyd,^a ^* Gersande Lena ^b and Julie A. Spicer ^b

^aDepartment of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand, and ^bCancer Research Laboratory, The University of Auckland, Private Bag 92019, Auckland, New Zealand
^*Correspondence e-mail: pdw.boyd@auckland.ac.nz

(Received 14 April 2008; accepted 14 April 2008; online 23 April 2008)

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, P 2₁ /n
a = 4.4998 (2) Å
b = 15.4499 (8) Å
c = 14.2036 (7) Å
β = 96.417 (1)°
V = 981.27 (8) Å³
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[F² > 2σ(F²)] = 0.049
wR(F²) = 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

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) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

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 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680801026X/bt2697sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680801026X/bt2697Isup2.hkl

checkCIF report

Comment top

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).

Related literature top

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

Experimental top

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.

Computing details top

Data collection: SMART (Siemens, 1995); cell refinement: SMART (Siemens, 1995); data reduction: SAINT (Siemens, 1995); 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).

Figures top

	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.

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

Crystal data top

C₁₀H₁₃NO₃	F(000) = 416
M_r = 195.21	D_x = 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 top

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

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.134	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0608P)² + 0.7105P] where P = (F_o² + 2F_c²)/3
1987 reflections	(Δ/σ)_max < 0.001
130 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³

Crystal data top

C₁₀H₁₃NO₃	V = 981.27 (8) Å³
M_r = 195.21	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 4.4998 (2) Å	µ = 0.10 mm⁻¹
b = 15.4499 (8) Å	T = 87 K
c = 14.2036 (7) Å	0.32 × 0.18 × 0.12 mm
β = 96.417 (1)°

Data collection top

Siemens SMART CCD diffractometer	1786 reflections with I > 2σ(I)
5759 measured reflections	R_int = 0.081
1987 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.134	H-atom parameters constrained
S = 1.02	Δρ_max = 0.30 e Å⁻³
1987 reflections	Δρ_min = −0.28 e Å⁻³
130 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	0.4226 (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 (Å²) top

	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, º) top

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, º) top

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) x−1/2, −y+3/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₀H₁₃NO₃
M_r	195.21
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	87
a, b, c (Å)	4.4998 (2), 15.4499 (8), 14.2036 (7)
β (°)	96.417 (1)
V (Å³)	981.27 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.32 × 0.18 × 0.12

Data collection
Diffractometer	Siemens SMART CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5759, 1987, 1786
R_int	0.081
(sin θ/λ)_max (Å⁻¹)	0.624

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.134, 1.02
No. of reflections	1987
No. of parameters	130
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.30, −0.28

Computer programs: SMART (Siemens, 1995), SAINT (Siemens, 1995), SIR92 (Altomare et al., 1993), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1ⁱ	0.82	2.01	2.8227 (17)	169.9

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

Acknowledgements

This work was supported by Auckland Division of the Cancer Society of New Zealand, UniServices and The University of Auckland Research Committee.

References

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