organic compounds
7-Hydroxymethyl-2-pivaloylamino-1,8-naphthyridine
aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, bDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia, and cDepartment of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711 103, India
*Correspondence e-mail: hkfun@usm.my
In the title compound, C14H17N3O2, the mean plane of the 1,8-naphthyridine ring system (r.m.s deviation = 0.020 Å) forms a dihedral angle of 23.4 (1)° with the acetamide moiety (r.m.s deviation = 0.001 Å). The molecular structure is stabilized by an intramolecular O—H⋯N hydrogen bond, which generates an S(5) ring motif. In the crystal, molecules are linked into inversion dimers by pairs of N—H⋯O hydrogen bonds, generating 18-membered R22(18) ring motifs.
Related literature
For general background to and the medicinal properties of 1,8-naphthyridine derivatives see: Badawneh et al. (2001); Litvinov (2004). For standard bond-length data, see: Allen et al. (1987). For hydrogen-bond motifs, see: Bernstein et al. (1995).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT; 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 and PLATON (Spek, 2009).
Supporting information
10.1107/S1600536813005527/rz5047sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536813005527/rz5047Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536813005527/rz5047Isup3.cml
To a stirred solution of 7-pivaloylamino-[1,8]naphthyridine-2-carbaldehyde (514 mg, 2 mmol) in dry THF was added NaBH4 (40 mg, 1mmol) at 0°C and the resulting mixture was stirred for half an hour at room temperature under nitrogen atmosphere. After evaporation of the solvent, water was added to it and then the reaction mixture was extracted with dichloromethane thrice. The organic layer was dried over anhydrous sodium sulphate and then evaporated under reduced pressure. The crude solid was purified through
(silica gel, 60-120 mesh) using ethyl acetate as to afford a pure brown crystalline solid. Yield: 87%. M.p. 135-137 °CAtoms H1N3 and H1O2 were located in a difference Fourier map and refined freely [N–H = 0.83 (2) Å and O–H 0.86 (3) Å]. The remaining H atoms were positioned geometrically and refined using a riding model with C–H = 0.93-0.97 Å and Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating-group model was applied for the methyl groups.
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); 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) and PLATON (Spek, 2009).C14H17N3O2 | F(000) = 552 |
Mr = 259.31 | Dx = 1.284 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 4518 reflections |
a = 14.7026 (3) Å | θ = 2.8–30.1° |
b = 6.2586 (1) Å | µ = 0.09 mm−1 |
c = 14.7035 (3) Å | T = 297 K |
β = 97.447 (2)° | Plate, brown |
V = 1341.57 (4) Å3 | 0.51 × 0.46 × 0.08 mm |
Z = 4 |
Bruker SMART APEXII CCD area-detector diffractometer | 3949 independent reflections |
Radiation source: fine-focus sealed tube | 2551 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.042 |
ϕ and ω scans | θmax = 30.2°, θmin = 2.8° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −20→20 |
Tmin = 0.956, Tmax = 0.993 | k = −8→8 |
20410 measured reflections | l = −20→19 |
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)] = 0.074 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.148 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.14 | w = 1/[σ2(Fo2) + (0.0366P)2 + 0.506P] where P = (Fo2 + 2Fc2)/3 |
3949 reflections | (Δ/σ)max = 0.001 |
183 parameters | Δρmax = 0.21 e Å−3 |
0 restraints | Δρmin = −0.14 e Å−3 |
C14H17N3O2 | V = 1341.57 (4) Å3 |
Mr = 259.31 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 14.7026 (3) Å | µ = 0.09 mm−1 |
b = 6.2586 (1) Å | T = 297 K |
c = 14.7035 (3) Å | 0.51 × 0.46 × 0.08 mm |
β = 97.447 (2)° |
Bruker SMART APEXII CCD area-detector diffractometer | 3949 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | 2551 reflections with I > 2σ(I) |
Tmin = 0.956, Tmax = 0.993 | Rint = 0.042 |
20410 measured reflections |
R[F2 > 2σ(F2)] = 0.074 | 0 restraints |
wR(F2) = 0.148 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.14 | Δρmax = 0.21 e Å−3 |
3949 reflections | Δρmin = −0.14 e Å−3 |
183 parameters |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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 | ||
O1 | 0.70708 (11) | −0.0049 (3) | 0.72243 (11) | 0.0731 (5) | |
O2 | 1.20193 (11) | 0.4754 (2) | 0.50680 (10) | 0.0564 (4) | |
N1 | 0.93270 (10) | 0.1958 (2) | 0.60449 (9) | 0.0398 (4) | |
N2 | 1.08422 (10) | 0.2310 (2) | 0.58087 (9) | 0.0403 (4) | |
C1 | 1.01722 (12) | 0.1059 (3) | 0.60905 (10) | 0.0369 (4) | |
C2 | 1.16763 (13) | 0.1520 (3) | 0.58648 (11) | 0.0424 (4) | |
C3 | 1.19173 (15) | −0.0552 (3) | 0.61930 (12) | 0.0509 (5) | |
H3A | 1.2519 | −0.1032 | 0.6226 | 0.061* | |
C4 | 1.12550 (14) | −0.1827 (3) | 0.64593 (12) | 0.0495 (5) | |
H4A | 1.1396 | −0.3206 | 0.6668 | 0.059* | |
C5 | 1.03554 (13) | −0.1052 (3) | 0.64177 (11) | 0.0410 (4) | |
C6 | 0.96182 (14) | −0.2230 (3) | 0.66823 (11) | 0.0468 (5) | |
H6A | 0.9707 | −0.3639 | 0.6876 | 0.056* | |
C7 | 0.87830 (14) | −0.1325 (3) | 0.66566 (12) | 0.0475 (5) | |
H7A | 0.8296 | −0.2073 | 0.6850 | 0.057* | |
C8 | 0.86672 (13) | 0.0803 (3) | 0.63253 (11) | 0.0406 (4) | |
N3 | 0.78116 (12) | 0.1817 (3) | 0.62256 (12) | 0.0490 (4) | |
C9 | 0.70570 (14) | 0.1334 (3) | 0.66391 (14) | 0.0505 (5) | |
C10 | 0.61984 (14) | 0.2648 (3) | 0.63154 (15) | 0.0578 (6) | |
C11 | 0.59481 (17) | 0.2364 (5) | 0.52733 (18) | 0.0814 (8) | |
H11A | 0.5892 | 0.0869 | 0.5130 | 0.122* | |
H11B | 0.6420 | 0.2979 | 0.4962 | 0.122* | |
H11C | 0.5376 | 0.3066 | 0.5077 | 0.122* | |
C12 | 0.54109 (18) | 0.1846 (5) | 0.6811 (2) | 0.0986 (10) | |
H12A | 0.5286 | 0.0376 | 0.6656 | 0.148* | |
H12B | 0.4872 | 0.2687 | 0.6627 | 0.148* | |
H12C | 0.5580 | 0.1973 | 0.7462 | 0.148* | |
C13 | 0.63721 (16) | 0.5019 (4) | 0.65370 (17) | 0.0688 (6) | |
H13A | 0.6540 | 0.5190 | 0.7186 | 0.103* | |
H13B | 0.5824 | 0.5822 | 0.6344 | 0.103* | |
H13C | 0.6860 | 0.5530 | 0.6220 | 0.103* | |
C14 | 1.23927 (14) | 0.2947 (3) | 0.55470 (14) | 0.0536 (5) | |
H14A | 1.2810 | 0.3412 | 0.6075 | 0.064* | |
H14B | 1.2745 | 0.2136 | 0.5152 | 0.064* | |
H1N3 | 0.7793 (14) | 0.288 (4) | 0.5889 (14) | 0.057 (6)* | |
H1O2 | 1.1439 (18) | 0.474 (4) | 0.5097 (18) | 0.087 (9)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0823 (11) | 0.0626 (10) | 0.0797 (11) | −0.0054 (9) | 0.0311 (9) | 0.0198 (9) |
O2 | 0.0555 (9) | 0.0436 (8) | 0.0725 (10) | 0.0026 (7) | 0.0170 (8) | 0.0102 (7) |
N1 | 0.0502 (9) | 0.0312 (8) | 0.0379 (7) | 0.0001 (7) | 0.0052 (6) | 0.0041 (6) |
N2 | 0.0505 (9) | 0.0323 (8) | 0.0381 (7) | 0.0023 (7) | 0.0061 (6) | 0.0028 (6) |
C1 | 0.0543 (11) | 0.0285 (9) | 0.0277 (8) | 0.0023 (8) | 0.0041 (7) | −0.0003 (7) |
C2 | 0.0531 (11) | 0.0408 (10) | 0.0333 (8) | 0.0059 (9) | 0.0058 (8) | −0.0014 (7) |
C3 | 0.0610 (13) | 0.0464 (12) | 0.0453 (10) | 0.0178 (10) | 0.0074 (9) | 0.0020 (9) |
C4 | 0.0760 (14) | 0.0356 (10) | 0.0373 (9) | 0.0169 (10) | 0.0082 (9) | 0.0056 (8) |
C5 | 0.0648 (12) | 0.0305 (9) | 0.0276 (8) | 0.0050 (8) | 0.0060 (8) | −0.0004 (7) |
C6 | 0.0770 (14) | 0.0275 (9) | 0.0354 (9) | 0.0005 (9) | 0.0058 (9) | 0.0041 (7) |
C7 | 0.0673 (13) | 0.0343 (10) | 0.0415 (10) | −0.0090 (9) | 0.0087 (9) | 0.0036 (8) |
C8 | 0.0524 (11) | 0.0351 (9) | 0.0339 (8) | −0.0032 (8) | 0.0035 (8) | −0.0002 (7) |
N3 | 0.0524 (10) | 0.0409 (9) | 0.0547 (10) | −0.0029 (8) | 0.0105 (8) | 0.0112 (8) |
C9 | 0.0579 (12) | 0.0413 (11) | 0.0538 (11) | −0.0123 (9) | 0.0132 (9) | −0.0048 (9) |
C10 | 0.0519 (12) | 0.0484 (12) | 0.0749 (14) | −0.0070 (10) | 0.0151 (11) | −0.0055 (11) |
C11 | 0.0617 (15) | 0.0837 (19) | 0.0930 (18) | 0.0035 (13) | −0.0122 (13) | −0.0208 (15) |
C12 | 0.0694 (17) | 0.084 (2) | 0.152 (3) | −0.0073 (15) | 0.0491 (18) | 0.009 (2) |
C13 | 0.0699 (15) | 0.0540 (14) | 0.0838 (16) | −0.0001 (12) | 0.0141 (12) | −0.0100 (12) |
C14 | 0.0532 (12) | 0.0512 (12) | 0.0571 (12) | 0.0051 (10) | 0.0094 (9) | 0.0030 (10) |
O1—C9 | 1.219 (2) | C8—N3 | 1.399 (2) |
O2—C14 | 1.406 (2) | N3—C9 | 1.366 (2) |
O2—H1O2 | 0.86 (3) | N3—H1N3 | 0.83 (2) |
N1—C8 | 1.318 (2) | C9—C10 | 1.530 (3) |
N1—C1 | 1.358 (2) | C10—C12 | 1.531 (3) |
N2—C2 | 1.315 (2) | C10—C13 | 1.534 (3) |
N2—C1 | 1.364 (2) | C10—C11 | 1.539 (3) |
C1—C5 | 1.420 (2) | C11—H11A | 0.9600 |
C2—C3 | 1.412 (3) | C11—H11B | 0.9600 |
C2—C14 | 1.501 (3) | C11—H11C | 0.9600 |
C3—C4 | 1.356 (3) | C12—H12A | 0.9600 |
C3—H3A | 0.9300 | C12—H12B | 0.9600 |
C4—C5 | 1.403 (3) | C12—H12C | 0.9600 |
C4—H4A | 0.9300 | C13—H13A | 0.9600 |
C5—C6 | 1.407 (3) | C13—H13B | 0.9600 |
C6—C7 | 1.348 (3) | C13—H13C | 0.9600 |
C6—H6A | 0.9300 | C14—H14A | 0.9700 |
C7—C8 | 1.421 (3) | C14—H14B | 0.9700 |
C7—H7A | 0.9300 | ||
C14—O2—H1O2 | 106.9 (18) | N3—C9—C10 | 115.32 (18) |
C8—N1—C1 | 117.60 (15) | C9—C10—C12 | 108.7 (2) |
C2—N2—C1 | 117.98 (15) | C9—C10—C13 | 110.25 (18) |
N1—C1—N2 | 116.06 (15) | C12—C10—C13 | 109.4 (2) |
N1—C1—C5 | 122.31 (17) | C9—C10—C11 | 109.20 (18) |
N2—C1—C5 | 121.63 (16) | C12—C10—C11 | 109.8 (2) |
N2—C2—C3 | 123.87 (18) | C13—C10—C11 | 109.6 (2) |
N2—C2—C14 | 116.29 (16) | C10—C11—H11A | 109.5 |
C3—C2—C14 | 119.83 (17) | C10—C11—H11B | 109.5 |
C4—C3—C2 | 118.79 (18) | H11A—C11—H11B | 109.5 |
C4—C3—H3A | 120.6 | C10—C11—H11C | 109.5 |
C2—C3—H3A | 120.6 | H11A—C11—H11C | 109.5 |
C3—C4—C5 | 119.48 (17) | H11B—C11—H11C | 109.5 |
C3—C4—H4A | 120.3 | C10—C12—H12A | 109.5 |
C5—C4—H4A | 120.3 | C10—C12—H12B | 109.5 |
C4—C5—C6 | 124.22 (17) | H12A—C12—H12B | 109.5 |
C4—C5—C1 | 118.24 (17) | C10—C12—H12C | 109.5 |
C6—C5—C1 | 117.54 (17) | H12A—C12—H12C | 109.5 |
C7—C6—C5 | 120.21 (17) | H12B—C12—H12C | 109.5 |
C7—C6—H6A | 119.9 | C10—C13—H13A | 109.5 |
C5—C6—H6A | 119.9 | C10—C13—H13B | 109.5 |
C6—C7—C8 | 118.16 (18) | H13A—C13—H13B | 109.5 |
C6—C7—H7A | 120.9 | C10—C13—H13C | 109.5 |
C8—C7—H7A | 120.9 | H13A—C13—H13C | 109.5 |
N1—C8—N3 | 113.99 (16) | H13B—C13—H13C | 109.5 |
N1—C8—C7 | 124.12 (18) | O2—C14—C2 | 112.97 (16) |
N3—C8—C7 | 121.81 (18) | O2—C14—H14A | 109.0 |
C9—N3—C8 | 128.60 (18) | C2—C14—H14A | 109.0 |
C9—N3—H1N3 | 118.5 (15) | O2—C14—H14B | 109.0 |
C8—N3—H1N3 | 112.8 (15) | C2—C14—H14B | 109.0 |
O1—C9—N3 | 122.1 (2) | H14A—C14—H14B | 107.8 |
O1—C9—C10 | 122.61 (19) | ||
C8—N1—C1—N2 | −178.99 (14) | C5—C6—C7—C8 | 2.3 (3) |
C8—N1—C1—C5 | 0.6 (2) | C1—N1—C8—N3 | −177.86 (14) |
C2—N2—C1—N1 | 178.24 (14) | C1—N1—C8—C7 | −1.0 (2) |
C2—N2—C1—C5 | −1.3 (2) | C6—C7—C8—N1 | −0.4 (3) |
C1—N2—C2—C3 | 0.5 (2) | C6—C7—C8—N3 | 176.20 (16) |
C1—N2—C2—C14 | 179.94 (15) | N1—C8—N3—C9 | −162.20 (18) |
N2—C2—C3—C4 | 0.7 (3) | C7—C8—N3—C9 | 20.9 (3) |
C14—C2—C3—C4 | −178.71 (17) | C8—N3—C9—O1 | 5.0 (3) |
C2—C3—C4—C5 | −1.1 (3) | C8—N3—C9—C10 | −174.93 (18) |
C3—C4—C5—C6 | −179.53 (17) | O1—C9—C10—C12 | −2.5 (3) |
C3—C4—C5—C1 | 0.3 (2) | N3—C9—C10—C12 | 177.52 (19) |
N1—C1—C5—C4 | −178.57 (15) | O1—C9—C10—C13 | 117.4 (2) |
N2—C1—C5—C4 | 0.9 (2) | N3—C9—C10—C13 | −62.6 (2) |
N1—C1—C5—C6 | 1.3 (2) | O1—C9—C10—C11 | −122.2 (2) |
N2—C1—C5—C6 | −179.22 (15) | N3—C9—C10—C11 | 57.8 (2) |
C4—C5—C6—C7 | 177.13 (17) | N2—C2—C14—O2 | −12.0 (2) |
C1—C5—C6—C7 | −2.7 (2) | C3—C2—C14—O2 | 167.53 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H1N3···O2i | 0.83 (2) | 2.09 (2) | 2.900 (2) | 168 (2) |
O2—H1O2···N2 | 0.86 (3) | 2.10 (3) | 2.648 (2) | 121 (2) |
Symmetry code: (i) −x+2, −y+1, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C14H17N3O2 |
Mr | 259.31 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 297 |
a, b, c (Å) | 14.7026 (3), 6.2586 (1), 14.7035 (3) |
β (°) | 97.447 (2) |
V (Å3) | 1341.57 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.51 × 0.46 × 0.08 |
Data collection | |
Diffractometer | Bruker SMART APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2009) |
Tmin, Tmax | 0.956, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 20410, 3949, 2551 |
Rint | 0.042 |
(sin θ/λ)max (Å−1) | 0.708 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.074, 0.148, 1.14 |
No. of reflections | 3949 |
No. of parameters | 183 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.21, −0.14 |
Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H1N3···O2i | 0.83 (2) | 2.09 (2) | 2.900 (2) | 168 (2) |
O2—H1O2···N2 | 0.86 (3) | 2.10 (3) | 2.648 (2) | 121 (2) |
Symmetry code: (i) −x+2, −y+1, −z+1. |
Acknowledgements
The authors thank Universiti Sains Malaysia (USM) for the RUC grant (Structure Determination of 50 kDa Outer Membrane Proteins From S.typhi By X-ray Protein Crystallography, No. 1001/PSKBP/8630013) and APEX DE2012 grant (No.1002/PFIZIK/910323). The authors also thank the CSIR and DST, Government of India, for financial support.
References
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1,8-Naphthyridine system is of great interest due to their broad application in medicine as they are potentially useful as antihypertensives, antitumor agents, immunostimulants, and herbicide safeners (Badawneh et al., 2001; Litvinov, 2004). Herein, we report the crystal structure of 2-pivaloylamino-7-hydroxymethyl-[1,8]naphthyridine.
In the title molecule, Fig. 1, the mean plane of [1,8]naphthyridine ring system (N1/N2/C1-C8, r.m.s deviation = 0.020 Å) forms a dihedral angle of 23.4 (1)° with the acetamide moiety (O1/N3/C9/C10, r.m.s deviation = 0.001 Å). Bond lengths (Allen et al., 1987) and angles are within normal ranges. The molecular structure is stabilized by an intramolecular O2–H1O2···N2 (Table 1) hydrogen bond, which generates an S(5) ring motif (Bernstein et al., 1995).
In the crystal, Fig. 2, molecules are linked into inversion dimers by pairs of intermolecular N3–H1N3···O2 (Table 1) hydrogen bonds, generating eighteen-membered R22(18) ring motifs (Bernstein et al., 1995).