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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3259.
Published online 2009 November 28. doi:  10.1107/S1600536809050429
PMCID: PMC2972179

4-Chloro-7-hydr­oxy-6-methyl-1,7-naphthyridin-8(7H)-one

Abstract

The title compound, C9H7ClN2O2, was prepared by reaction of methyl 4-chloro-3-(prop-1-yn­yl)picolinate with hydroxy­l­amine in MeOH/KOH solution. The two essentially planar mol­ecules which make up the asymmetric unit have almost identical geometries and and are linked into dimeric aggregates via pairs of O—H(...)O hydrogen bonds. These aggregates have almost perfect inversion symmetry; however, quite unusually, the inversion center of the dimer does not coincide with the crystallographic inversion center.

Related literature

For the synthesis, see: Knight et al. (2002 [triangle]). For the structures of related compounds with a similar bicyclic framework, see: Ikeura et al. (1998 [triangle]); Natsugari et al. (1995 [triangle]). For structural analysis, see: Spek (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3259-scheme1.jpg

Experimental

Crystal data

  • C9H7ClN2O2
  • M r = 210.62
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3259-efi1.jpg
  • a = 9.3983 (4) Å
  • b = 13.8786 (5) Å
  • c = 13.5643 (5) Å
  • β = 107.663 (3)°
  • V = 1685.86 (11) Å3
  • Z = 8
  • Cu Kα radiation
  • μ = 3.80 mm−1
  • T = 100 K
  • 0.14 × 0.12 × 0.08 mm

Data collection

  • Bruker APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.618, T max = 0.751
  • 12070 measured reflections
  • 3061 independent reflections
  • 2420 reflections with I > 2σ(I)
  • R int = 0.032

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.115
  • S = 1.05
  • 3061 reflections
  • 255 parameters
  • H-atom parameters constrained
  • Δρmax = 0.50 e Å−3
  • Δρmin = −0.41 e Å−3

Data collection: APEX2 (Bruker, 2007 [triangle]); cell refinement: SAINT (Bruker, 2007 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809050429/dn2516sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050429/dn2516Isup2.hkl

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

supplementary crystallographic information

Comment

The title compound was obtained using the reaction of of methyl 4-chloro-3-(prop-1-ynyl)picolinate with hydroxylamine in MeOH/KOH solution (Knight et al., 2002). The structural formula of the product was confirmed by the present study (Fig. 1).

There are two independent molecules in the structure, which show almost identical geometry. The molecules are essentially planar (with the exception of methyl H atoms) and their parameters are quite similar to those found in related structures with analogous carbon-nitrogen bicyclic framework (Ikeura et al., 1998; Natsugari et al., 1995). To the best of our knowledge, however, this is the first structurally characterized system of this kind with the O-substitution at the N atom next to C=O group.

The molecules in the asymmetric unit of the title compound are linked into dimeric aggregates via H-bonds (Table 1). These aggregates have almost ideal inversion symmetry, however, quite unusually, the inversion center of the dimer does not coincide with the crystallographic inversion center.

Experimental

Warm solutions (50°C) of hydroxylamine hydrochloride (199.0 mg, 2.86 mmol, 6 eq) in methanol (2.0 M, 1.43 ml) and potassium hydroxide (241.0 mg, 4.29 mmol, 9 eq) in methanol (4.0 M, 1.07 ml) were mixed; the resulting solution was cooled to below 40°C and potassium chloride precipitated out. The precipitate was filtered and the filtrate was added to a vial containing methyl 4-chloro-3-(prop-1-ynyl)picolinate (100.0 mg, 0.4770 mmol); the flask containing the filtrate was rinsed with an additional 1 ml of MeOH and added to the reaction vial. The resulting mixture was then heated to reflux. A precipitate formed within 20 minutes. The reaction was monitored by LCMS; after consumption of starting material (about 75 min), the mixture was removed from heat and cooled to room temperature, diluted with ether and the precipitate was collected. To the precipitate was added minimal amount of acetic acid to quench the mixture. The mixture was then triturated in ethyl acetate and filtered. The filtrate was collected, concentrated and the solid dried to give 26 mg (26%) of the title compound. A small sample was dissolved in methanol:dichloromethane (1:1) and heated at 50°C to dryness to obtain crystals of sufficient quality for X-ray diffraction experiment. LC—MS m/z (% relative intensity, ion): 211.0 (100.0%), 213.0 (32.0%), 212.0 (9.9%), 214.0 (3.2%). 1H NMR (400 MHz, DMSO-d6) δ p.p.m. 2.46 (s, 3H) 6.67 (br. s., 1H) 7.88 (br. s., 1H) 8.65 (br. s., 1H) 11.62 (br. s., 1H).

Refinement

All H atoms were placed in geometrically calculated positions (C—H 0.98 Å and 0.95 Å for methyl and aromatic CH-groups; O—H 0.84 Å) and included in the refinement in riding motion approximation. The Uiso(H) were set to 1.2Ueq of the carrying atom (1.5Ueq for methyl and hydroxyl H atoms).

Two independent molecules in the structure of the title compound are related by almost ideal non-crystallographic inversion center, which prompted us to perform additional checks on the presence of higher genuine symmetry by careful inspection of atomic coordinates as well as by using ADDSYM option in PLATON (Spek, 2009). Nevertheless, no unaccounted crystallographic symmetry was detected.

Figures

Fig. 1.
Molecular structure of the title compound, showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius. H-bonds are shown as dashed lines.

Crystal data

C9H7ClN2O2F(000) = 864
Mr = 210.62Dx = 1.660 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybcCell parameters from 4820 reflections
a = 9.3983 (4) Åθ = 4.7–67.9°
b = 13.8786 (5) ŵ = 3.80 mm1
c = 13.5643 (5) ÅT = 100 K
β = 107.663 (3)°Block, light yellow
V = 1685.86 (11) Å30.14 × 0.12 × 0.08 mm
Z = 8

Data collection

Bruker APEXII CCD area-detector diffractometer3061 independent reflections
Radiation source: fine-focus sealed tube2420 reflections with I > 2σ(I)
graphiteRint = 0.032
phi and ω scansθmax = 68.1°, θmin = 4.7°
Absorption correction: multi-scan (SADABS; Bruker, 2001)h = −11→11
Tmin = 0.618, Tmax = 0.751k = −13→16
12070 measured reflectionsl = −16→16

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.115H-atom parameters constrained
S = 1.05w = 1/[σ2(Fo2) + (0.0643P)2 + 0.6521P] where P = (Fo2 + 2Fc2)/3
3061 reflections(Δ/σ)max < 0.001
255 parametersΔρmax = 0.50 e Å3
0 restraintsΔρmin = −0.41 e Å3

Special details

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 > 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)

xyzUiso*/Ueq
Cl11−0.07931 (6)0.29765 (4)0.57976 (4)0.02505 (17)
O110.62329 (17)0.16036 (11)0.68417 (13)0.0229 (4)
H11C0.69500.19930.69680.034*
O120.62280 (17)0.34923 (11)0.68384 (12)0.0220 (4)
N110.3605 (2)0.45541 (13)0.64550 (14)0.0199 (4)
N120.4903 (2)0.21085 (13)0.66186 (14)0.0175 (4)
C110.2323 (2)0.50128 (17)0.63118 (17)0.0213 (5)
H11A0.23430.56970.63370.026*
C120.0938 (3)0.45514 (17)0.61247 (16)0.0210 (5)
H12A0.00510.49120.60450.025*
C130.0903 (2)0.35705 (17)0.60603 (16)0.0186 (5)
C140.2232 (2)0.30333 (16)0.62197 (16)0.0171 (5)
C150.2303 (2)0.20137 (16)0.61942 (16)0.0179 (5)
H15A0.14060.16490.60330.021*
C160.3631 (2)0.15509 (16)0.63963 (16)0.0171 (5)
C170.4990 (2)0.30963 (16)0.66367 (16)0.0174 (5)
C180.3550 (2)0.35808 (16)0.64246 (16)0.0166 (5)
C190.3820 (3)0.04884 (15)0.63766 (17)0.0204 (5)
H19A0.28370.01790.61650.031*
H19B0.43900.02630.70680.031*
H19C0.43580.03230.58840.031*
Cl211.58399 (6)0.29188 (4)0.92532 (4)0.02425 (17)
O210.87294 (17)0.40291 (12)0.82957 (13)0.0275 (4)
H21C0.80440.36160.81760.041*
O220.88743 (17)0.21429 (11)0.81342 (12)0.0228 (4)
N211.1594 (2)0.11748 (14)0.85899 (14)0.0202 (4)
N221.0090 (2)0.35700 (13)0.84478 (14)0.0187 (4)
C211.2917 (3)0.07633 (17)0.87918 (17)0.0213 (5)
H21A1.29600.00790.87890.026*
C221.4260 (3)0.12739 (17)0.90091 (17)0.0221 (5)
H22A1.51860.09440.91530.026*
C231.4211 (2)0.22576 (17)0.90105 (16)0.0188 (5)
C241.2824 (2)0.27445 (16)0.88048 (16)0.0163 (5)
C251.2672 (2)0.37650 (16)0.88112 (16)0.0175 (5)
H25A1.35310.41610.89290.021*
C261.1319 (3)0.41747 (16)0.86517 (17)0.0180 (5)
C271.0071 (2)0.25806 (16)0.83737 (17)0.0184 (5)
C281.1554 (2)0.21492 (16)0.86006 (16)0.0167 (5)
C291.1054 (3)0.52295 (16)0.86981 (18)0.0225 (5)
H29A1.20030.55750.88250.034*
H29B1.06290.53640.92600.034*
H29C1.03570.54430.80390.034*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl110.0151 (3)0.0280 (3)0.0313 (3)−0.0015 (2)0.0058 (2)0.0012 (2)
O110.0132 (8)0.0163 (8)0.0371 (9)0.0040 (6)0.0046 (7)0.0022 (7)
O120.0165 (8)0.0176 (8)0.0311 (9)−0.0031 (7)0.0061 (7)0.0023 (7)
N110.0227 (10)0.0143 (9)0.0217 (10)0.0003 (8)0.0052 (8)0.0002 (8)
N120.0155 (10)0.0133 (9)0.0238 (10)0.0022 (7)0.0059 (8)0.0011 (8)
C110.0249 (12)0.0154 (11)0.0222 (11)0.0031 (10)0.0050 (9)−0.0002 (9)
C120.0209 (12)0.0219 (12)0.0201 (11)0.0072 (10)0.0059 (9)−0.0002 (9)
C130.0173 (11)0.0207 (12)0.0172 (11)0.0007 (9)0.0041 (9)0.0005 (9)
C140.0190 (12)0.0173 (11)0.0163 (11)0.0008 (9)0.0070 (9)0.0007 (9)
C150.0171 (11)0.0174 (11)0.0189 (11)−0.0040 (9)0.0050 (9)−0.0010 (9)
C160.0199 (11)0.0154 (11)0.0156 (10)−0.0022 (9)0.0048 (9)0.0007 (9)
C170.0188 (11)0.0163 (11)0.0177 (11)0.0012 (9)0.0062 (9)0.0019 (9)
C180.0189 (12)0.0139 (11)0.0167 (11)0.0002 (9)0.0051 (9)0.0001 (9)
C190.0230 (11)0.0133 (11)0.0223 (11)−0.0006 (9)0.0033 (9)−0.0001 (9)
Cl210.0159 (3)0.0256 (3)0.0303 (3)−0.0007 (2)0.0057 (2)0.0016 (2)
O210.0126 (8)0.0200 (8)0.0473 (11)0.0039 (7)0.0053 (7)−0.0038 (8)
O220.0171 (8)0.0211 (8)0.0297 (9)−0.0029 (7)0.0063 (7)0.0010 (7)
N210.0248 (10)0.0143 (9)0.0217 (10)0.0000 (8)0.0074 (8)−0.0010 (8)
N220.0150 (9)0.0149 (10)0.0255 (10)0.0037 (8)0.0051 (8)−0.0004 (8)
C210.0255 (12)0.0147 (11)0.0234 (12)0.0033 (10)0.0069 (10)−0.0004 (9)
C220.0231 (12)0.0199 (12)0.0244 (12)0.0065 (10)0.0089 (10)0.0018 (10)
C230.0172 (11)0.0221 (12)0.0167 (11)0.0000 (9)0.0045 (9)0.0000 (9)
C240.0188 (12)0.0163 (11)0.0138 (11)0.0012 (9)0.0050 (9)0.0009 (9)
C250.0184 (11)0.0164 (11)0.0174 (11)−0.0018 (9)0.0047 (9)−0.0005 (9)
C260.0204 (11)0.0149 (11)0.0191 (11)−0.0014 (9)0.0065 (9)0.0012 (9)
C270.0191 (12)0.0170 (11)0.0190 (11)0.0000 (9)0.0057 (9)0.0017 (9)
C280.0182 (12)0.0161 (11)0.0166 (11)−0.0014 (9)0.0061 (9)−0.0010 (9)
C290.0236 (12)0.0155 (12)0.0268 (12)0.0013 (10)0.0053 (10)0.0001 (10)

Geometric parameters (Å, °)

Cl11—C131.733 (2)Cl21—C231.729 (2)
O11—N121.384 (2)O21—N221.387 (2)
O11—H11C0.8400O21—H21C0.8405
O12—C171.240 (3)O22—C271.232 (3)
N11—C111.323 (3)N21—C211.320 (3)
N11—C181.352 (3)N21—C281.353 (3)
N12—C171.373 (3)N22—C271.377 (3)
N12—C161.378 (3)N22—C261.386 (3)
C11—C121.403 (3)C21—C221.399 (3)
C11—H11A0.9500C21—H21A0.9500
C12—C131.364 (3)C22—C231.366 (3)
C12—H12A0.9500C22—H22A0.9500
C13—C141.414 (3)C23—C241.419 (3)
C14—C181.407 (3)C24—C281.408 (3)
C14—C151.418 (3)C24—C251.424 (3)
C15—C161.356 (3)C25—C261.349 (3)
C15—H15A0.9500C25—H25A0.9500
C16—C191.486 (3)C26—C291.489 (3)
C17—C181.459 (3)C27—C281.462 (3)
C19—H19A0.9800C29—H29A0.9800
C19—H19B0.9800C29—H29B0.9800
C19—H19C0.9800C29—H29C0.9800
N12—O11—H11C109.5N22—O21—H21C109.5
C11—N11—C18116.9 (2)C21—N21—C28117.2 (2)
C17—N12—C16127.42 (19)C27—N22—C26127.62 (19)
C17—N12—O11117.17 (18)C27—N22—O21117.13 (18)
C16—N12—O11115.41 (17)C26—N22—O21115.25 (17)
N11—C11—C12124.1 (2)N21—C21—C22123.9 (2)
N11—C11—H11A118.0N21—C21—H21A118.0
C12—C11—H11A118.0C22—C21—H21A118.0
C13—C12—C11118.1 (2)C23—C22—C21118.5 (2)
C13—C12—H12A121.0C23—C22—H22A120.7
C11—C12—H12A121.0C21—C22—H22A120.7
C12—C13—C14120.9 (2)C22—C23—C24120.4 (2)
C12—C13—Cl11119.42 (18)C22—C23—Cl21120.15 (18)
C14—C13—Cl11119.71 (18)C24—C23—Cl21119.49 (18)
C18—C14—C13115.4 (2)C28—C24—C23115.6 (2)
C18—C14—C15119.9 (2)C28—C24—C25120.3 (2)
C13—C14—C15124.6 (2)C23—C24—C25124.1 (2)
C16—C15—C14121.0 (2)C26—C25—C24120.7 (2)
C16—C15—H15A119.5C26—C25—H25A119.7
C14—C15—H15A119.5C24—C25—H25A119.7
C15—C16—N12117.5 (2)C25—C26—N22117.7 (2)
C15—C16—C19125.0 (2)C25—C26—C29124.7 (2)
N12—C16—C19117.43 (19)N22—C26—C29117.6 (2)
O12—C17—N12119.6 (2)O22—C27—N22120.1 (2)
O12—C17—C18126.2 (2)O22—C27—C28126.1 (2)
N12—C17—C18114.20 (19)N22—C27—C28113.74 (19)
N11—C18—C14124.6 (2)N21—C28—C24124.4 (2)
N11—C18—C17115.49 (19)N21—C28—C27115.7 (2)
C14—C18—C17119.9 (2)C24—C28—C27119.9 (2)
C16—C19—H19A109.5C26—C29—H29A109.5
C16—C19—H19B109.5C26—C29—H29B109.5
H19A—C19—H19B109.5H29A—C29—H29B109.5
C16—C19—H19C109.5C26—C29—H29C109.5
H19A—C19—H19C109.5H29A—C29—H29C109.5
H19B—C19—H19C109.5H29B—C29—H29C109.5

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O11—H11C···O220.842.022.675 (2)134
O21—H21C···O120.842.092.677 (2)127

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DN2516).

References

  • Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Ikeura, Y., Ishichi, Y., Tanaka, T., Fujishima, A., Murabayashi, M., Kawada, M., Ishimaru, T., Kamo, I., Doi, T. & Natsugari, H. (1998). J. Med. Chem. 41, 4232–4239. [PubMed]
  • Knight, D. W., Lewis, P. B. M., Abdul Malik, K. M., Mshvidobadze, E. V. & Vasilevsky, S. G. (2002). Tetrahedron Lett. 43, 9187–9189.
  • Natsugari, H., Ikeura, Y., Kiyota, Y., Ishichi, Y., Ishimaru, T., Saga, O., Shirafuji, H., Tanaka, T., Kamo, I., Doi, T. & Otsuka, M. (1995). J. Med. Chem. 38, 3106–3120. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

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