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Acta Crystallogr Sect E Struct Rep Online. 2010 May 1; 66(Pt 5): o1010.
Published online 2010 April 2. doi:  10.1107/S1600536810011694
PMCID: PMC2979073

2-Chloro-8-methyl-3-[(pyrimidin-4-yl­oxy)meth­yl]quinoline

Abstract

In the title compound, C15H12ClN3O, the quinoline ring system is essentially planar, with a maximum deviation of 0.017 (1) Å. The crystal packing is stabilized by π–π stacking inter­actions between the quinoline rings of adjacent mol­ecule, with a centroid–centroid distance of 3.5913 (8) Å. A weak C—H(...)π contact is also observed between mol­ecules.

Related literature

For pyrimidine analogues, see: Svenstrup et al. (2008 [triangle]). For quinoline analogues, see: Roopan & Khan (2009 [triangle]); Khan et al. (2009 [triangle], 2010a [triangle],b [triangle]). For the biological activity and mode of action of alkyl­ating agent, see: Singer (1986 [triangle]). For the synthesis and regioselective alkyl­ation of 4(3H)-pyrimidone, see: Roopan et al. (2010 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]). For a structural discussion on hydrogen bonding, see: Bernstein et al. (1995 [triangle]).

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Object name is e-66-o1010-scheme1.jpg

Experimental

Crystal data

  • C15H12ClN3O
  • M r = 285.73
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1010-efi1.jpg
  • a = 11.9975 (2) Å
  • b = 8.45037 (15) Å
  • c = 12.95869 (19) Å
  • β = 96.7619 (16)°
  • V = 1304.66 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.29 mm−1
  • T = 295 K
  • 0.23 × 0.18 × 0.15 mm

Data collection

  • Oxford Xcalibur Eos (Nova) CCD detector diffractometer
  • Absorption correction: multi-scan (CrysAlis PRO RED; Oxford Diffraction, 2009 [triangle]) T min = 0.936, T max = 0.958
  • 13753 measured reflections
  • 2564 independent reflections
  • 2005 reflections with I > 2σ(I)
  • R int = 0.031

Refinement

  • R[F 2 > 2σ(F 2)] = 0.033
  • wR(F 2) = 0.089
  • S = 1.07
  • 2564 reflections
  • 182 parameters
  • H-atom parameters constrained
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.20 e Å−3

Data collection: CrysAlis PRO CCD (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis PRO CCD; data reduction: CrysAlis PRO RED (Oxford Diffraction, 2009 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]) and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810011694/fj2289sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810011694/fj2289Isup2.hkl

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

Acknowledgments

We thank the FIST program for the data collection at SSCU, IISc, Bangalore and Professor T. N. Guru Row, IISc, Bangalore, for his help with the data collection. FNK thanks the DST for Fast Track Proposal funding.

supplementary crystallographic information

Comment

Alkylating agents have been studied extensively both for their biological effects and for their mode of action (Singer et al., 1986). There have been over the past 25 years a veritable deluge of reviews, often focusing on a single aspect or agent or adduct. Direct alkylation of oxygens in pyrimidine nucleosides, under physiological conditions, has been known only since the middle 1970s. The pyrimidine analogues (Svenstrup et al., 2008) such as naturally occurring azacamptothecin based molecule have been focused of great interest by reason of their diversified biological activities. Thus, modifications of biologically active azacamptothecin synthons may lead to achieve the highly expected effective drugs. In connection with the program of synthesis and regioselective alkylation of 4(3H)-pyrimidone (Roopan et al., 2010), we report herein the synthesis of 2-chloro-8-methyl-3-[(pyrimidin-4-yloxy)methyl]quinoline.

In the molecule of the title compound, Fig. 1, bond lengths and angles are in normal ranges (Allen et al., 1987). The quinoline ring system (N1/C1–C9) is essentially planar, with a maximum deviation of -0.017 (1) Å for atom C1. The quinoline system (N1/C1–C9) makes a dihedral angle of 4.99 (6)° with the piyrimidone ring (N2/N3/C11–C14).

In the title molecule, there is a weak intramolecular C—H···O interaction, generating an S(5) graph-set motif (Bernstein et al., 1995) (Table 1). The crystal packing is stabilized by π-π stacking interactions between the benzene rings of the quinoline ring system of the molecules related by the symmetry operator (1-x, 1-y, -z) [centroid-to-centroid distance = 3.5913 (8) Å]. In addition, a weak C—H···π contact is also observed between molecules (Table 1). The packing diagram viewing down the b-axis is shown in Fig. 2.

Experimental

To a mixed well solution of 4(3H)-pyrimidone (96 mg, 1 mmol, in 5 ml DMSO), NaH (25 mg, 1 mmol) and 2-chloro-3-(chloromethyl)-8-methylquinoline (225 mg, 1 mmol) were added and the resulting mixture was refluxed for 1 h. Completion of the reaction was monitored by TLC. After the completion of the reaction, cooled and removed the excess of solvent under reduced pressure. Crushed ice was mixed with the residue. White solid was formed, filtered and dried, purified by column chromatography using hexane and ethylacetate as the eluant. The low polar compound was subjected into crystallization by solvent evaporation from a solution of the compound in chloroform.

Refinement

All H atoms were placed in geometrically idealised positions and constrained to ride on their parent atoms (C—H = 0.93, 0.96 and 0.97 Å) and Uiso(H) values were taken to be equal to 1.2 Ueq(C) for aromatic and methylene H atoms and 1.5Ueq(C) for methyl H atoms.

Figures

Fig. 1.
The molecular structure of the title molecule with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
Packing diagram of the title compound viewed down b-axis. All H atoms have been omitted for clarity.

Crystal data

C15H12ClN3OF(000) = 592
Mr = 285.73Dx = 1.455 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 1065 reflections
a = 11.9975 (2) Åθ = 2.5–26.0°
b = 8.45037 (15) ŵ = 0.29 mm1
c = 12.95869 (19) ÅT = 295 K
β = 96.7619 (16)°Prism, colourless
V = 1304.66 (4) Å30.23 × 0.18 × 0.15 mm
Z = 4

Data collection

Oxford Xcalibur Eos (Nova) CCD detector diffractometer2564 independent reflections
Radiation source: Enhance (Mo) X-ray Source2005 reflections with I > 2σ(I)
graphiteRint = 0.031
ω scansθmax = 26.0°, θmin = 2.5°
Absorption correction: multi-scan (CrysAlis PRO RED; Oxford Diffraction, 2009)h = −14→14
Tmin = 0.936, Tmax = 0.958k = −10→10
13753 measured reflectionsl = −15→15

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)] = 0.033Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.089H-atom parameters constrained
S = 1.07w = 1/[σ2(Fo2) + (0.0503P)2] where P = (Fo2 + 2Fc2)/3
2564 reflections(Δ/σ)max < 0.001
182 parametersΔρmax = 0.18 e Å3
0 restraintsΔρmin = −0.20 e Å3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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
Cl10.52448 (3)0.22861 (5)−0.21533 (3)0.0452 (2)
O10.35909 (9)0.13571 (11)0.06428 (7)0.0413 (4)
N10.66190 (10)0.38546 (12)−0.08362 (8)0.0315 (4)
N20.22497 (11)−0.02532 (14)−0.02386 (9)0.0398 (4)
N30.08616 (12)−0.14701 (16)0.06771 (13)0.0569 (6)
C10.57162 (12)0.30022 (16)−0.09125 (10)0.0297 (4)
C20.50756 (12)0.25855 (14)−0.01007 (10)0.0282 (4)
C30.54805 (12)0.31329 (15)0.08638 (10)0.0299 (4)
C40.69272 (13)0.46034 (15)0.20041 (11)0.0365 (5)
C50.78847 (14)0.54796 (16)0.20983 (12)0.0418 (5)
C60.84248 (13)0.58407 (16)0.12263 (12)0.0399 (5)
C70.80215 (13)0.53220 (16)0.02491 (11)0.0345 (5)
C80.70266 (12)0.43947 (15)0.01381 (10)0.0291 (4)
C90.64712 (12)0.40438 (15)0.10159 (10)0.0296 (4)
C100.40366 (12)0.16051 (16)−0.03229 (10)0.0327 (5)
C110.26755 (13)0.04265 (16)0.06302 (11)0.0344 (5)
C120.22415 (15)0.02264 (18)0.15667 (12)0.0459 (6)
C130.13310 (16)−0.0742 (2)0.15376 (15)0.0551 (7)
C140.13543 (15)−0.11672 (19)−0.01572 (14)0.0514 (6)
C150.86040 (14)0.57135 (18)−0.06845 (13)0.0465 (6)
H30.509700.290100.142800.0360*
H40.657400.437300.258800.0440*
H50.818500.584400.275000.0500*
H60.907500.644900.131200.0480*
H10A0.349100.21490−0.081000.0390*
H10B0.421400.05980−0.062400.0390*
H120.255200.072100.217500.0550*
H130.10170−0.090800.215200.0660*
H140.10390−0.16500−0.076800.0620*
H15A0.923900.63810−0.047800.0700*
H15B0.809200.62550−0.119000.0700*
H15C0.885300.47550−0.098200.0700*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0438 (3)0.0642 (3)0.0278 (2)−0.0083 (2)0.0045 (2)−0.0068 (2)
O10.0385 (7)0.0543 (6)0.0322 (6)−0.0162 (5)0.0092 (5)−0.0009 (5)
N10.0286 (7)0.0364 (6)0.0301 (6)0.0026 (5)0.0059 (5)0.0019 (5)
N20.0355 (8)0.0428 (7)0.0406 (7)−0.0044 (6)0.0027 (6)0.0005 (6)
N30.0425 (10)0.0507 (9)0.0792 (11)−0.0086 (7)0.0143 (8)0.0065 (8)
C10.0293 (8)0.0340 (7)0.0259 (7)0.0036 (6)0.0034 (6)−0.0007 (5)
C20.0268 (8)0.0278 (7)0.0303 (7)0.0045 (6)0.0046 (6)0.0023 (6)
C30.0307 (9)0.0319 (7)0.0280 (7)0.0033 (6)0.0078 (6)0.0029 (6)
C40.0409 (10)0.0368 (8)0.0313 (8)0.0009 (7)0.0025 (7)0.0009 (6)
C50.0469 (11)0.0396 (8)0.0362 (8)0.0005 (7)−0.0062 (7)−0.0046 (6)
C60.0315 (9)0.0359 (8)0.0507 (9)−0.0041 (7)−0.0015 (7)−0.0012 (7)
C70.0306 (9)0.0316 (8)0.0418 (8)0.0017 (6)0.0060 (7)0.0014 (6)
C80.0279 (8)0.0285 (7)0.0309 (7)0.0037 (6)0.0035 (6)0.0006 (5)
C90.0297 (8)0.0279 (7)0.0310 (7)0.0037 (6)0.0029 (6)0.0021 (5)
C100.0310 (9)0.0386 (8)0.0288 (7)−0.0009 (6)0.0054 (6)0.0011 (6)
C110.0295 (9)0.0343 (8)0.0399 (8)−0.0010 (6)0.0063 (7)0.0045 (6)
C120.0498 (11)0.0489 (9)0.0417 (9)−0.0058 (8)0.0165 (8)0.0004 (7)
C130.0533 (12)0.0523 (10)0.0647 (12)−0.0042 (9)0.0281 (10)0.0087 (9)
C140.0422 (11)0.0501 (10)0.0605 (11)−0.0089 (8)0.0008 (9)−0.0019 (8)
C150.0387 (10)0.0498 (10)0.0526 (10)−0.0108 (8)0.0119 (8)0.0019 (7)

Geometric parameters (Å, °)

Cl1—C11.7485 (14)C7—C81.421 (2)
O1—C101.4330 (16)C7—C151.504 (2)
O1—C111.3493 (18)C8—C91.4158 (19)
N1—C11.2948 (18)C11—C121.386 (2)
N1—C81.3770 (17)C12—C131.362 (3)
N2—C111.3126 (18)C3—H30.9300
N2—C141.337 (2)C4—H40.9300
N3—C131.338 (2)C5—H50.9300
N3—C141.317 (2)C6—H60.9300
C1—C21.4184 (19)C10—H10A0.9700
C2—C31.3672 (18)C10—H10B0.9700
C2—C101.496 (2)C12—H120.9300
C3—C91.410 (2)C13—H130.9300
C4—C51.360 (2)C14—H140.9300
C4—C91.4134 (19)C15—H15A0.9600
C5—C61.401 (2)C15—H15B0.9600
C6—C71.373 (2)C15—H15C0.9600
Cl1···C15i3.5264 (17)C5···H10Avi2.9800
Cl1···H10A2.8900C6···H10Avi2.8600
Cl1···H10B2.8400C7···H10Avi2.9500
Cl1···H14ii3.0800C10···H10Bv2.9600
O1···H32.3600C11···H15Bvi3.0700
N1···H15B2.7600C12···H15Bvi3.0300
N1···H15C2.8100H3···O12.3600
N2···H10A2.6700H3···H42.5100
N2···H10B2.5700H4···H32.5100
N2···H4iii2.9300H4···N2ix2.9300
N3···H15Aiv2.9400H5···C3x2.9800
N3···H15Cv2.8200H6···H15A2.3500
C1···C3vi3.5712 (19)H10A···Cl12.8900
C1···C11v3.476 (2)H10A···N22.6700
C2···C8vi3.5842 (19)H10A···C5vi2.9800
C2···C9vi3.5278 (18)H10A···C6vi2.8600
C3···C1vi3.5712 (19)H10A···C7vi2.9500
C7···C14v3.595 (2)H10B···Cl12.8400
C7···C10vi3.592 (2)H10B···N22.5700
C8···C2vi3.5842 (19)H10B···C2v2.9400
C8···C14v3.347 (2)H10B···C10v2.9600
C9···C2vi3.5278 (18)H10B···H10Bv2.5400
C10···C7vi3.592 (2)H14···Cl1xi3.0800
C10···C10v3.598 (2)H15A···N3xii2.9400
C11···C1v3.476 (2)H15A···H62.3500
C14···C8v3.347 (2)H15B···N12.7600
C14···C7v3.595 (2)H15B···C11vi3.0700
C15···Cl1vii3.5264 (17)H15B···C12vi3.0300
C2···H10Bv2.9400H15C···N12.8100
C3···H5viii2.9800H15C···N3v2.8200
C10—O1—C11117.49 (10)N3—C13—C12123.83 (17)
C1—N1—C8117.26 (11)N2—C14—N3128.27 (16)
C11—N2—C14114.85 (13)C2—C3—H3119.00
C13—N3—C14114.15 (15)C9—C3—H3119.00
Cl1—C1—N1116.09 (10)C5—C4—H4120.00
Cl1—C1—C2116.83 (10)C9—C4—H4120.00
N1—C1—C2127.08 (12)C4—C5—H5120.00
C1—C2—C3115.39 (12)C6—C5—H5120.00
C1—C2—C10120.44 (11)C5—C6—H6119.00
C3—C2—C10124.17 (12)C7—C6—H6119.00
C2—C3—C9121.02 (12)O1—C10—H10A110.00
C5—C4—C9119.75 (14)O1—C10—H10B110.00
C4—C5—C6120.81 (14)C2—C10—H10A110.00
C5—C6—C7121.88 (14)C2—C10—H10B110.00
C6—C7—C8118.03 (13)H10A—C10—H10B108.00
C6—C7—C15121.68 (14)C11—C12—H12122.00
C8—C7—C15120.29 (13)C13—C12—H12122.00
N1—C8—C7118.62 (12)N3—C13—H13118.00
N1—C8—C9121.15 (12)C12—C13—H13118.00
C7—C8—C9120.23 (12)N2—C14—H14116.00
C3—C9—C4122.63 (12)N3—C14—H14116.00
C3—C9—C8118.08 (12)C7—C15—H15A109.00
C4—C9—C8119.29 (13)C7—C15—H15B109.00
O1—C10—C2107.52 (10)C7—C15—H15C109.00
O1—C11—N2119.96 (13)H15A—C15—H15B109.00
O1—C11—C12116.72 (13)H15A—C15—H15C109.00
N2—C11—C12123.31 (14)H15B—C15—H15C109.00
C11—C12—C13115.58 (15)
C11—O1—C10—C2−176.75 (11)C2—C3—C9—C4−178.71 (13)
C10—O1—C11—N22.21 (19)C2—C3—C9—C80.9 (2)
C10—O1—C11—C12−178.68 (13)C9—C4—C5—C60.2 (2)
C8—N1—C1—Cl1−178.15 (10)C5—C4—C9—C3−179.87 (13)
C8—N1—C1—C21.6 (2)C5—C4—C9—C80.6 (2)
C1—N1—C8—C7179.47 (12)C4—C5—C6—C7−0.5 (2)
C1—N1—C8—C9−0.69 (19)C5—C6—C7—C80.0 (2)
C14—N2—C11—O1179.03 (13)C5—C6—C7—C15179.97 (14)
C14—N2—C11—C120.0 (2)C6—C7—C8—N1−179.40 (12)
C11—N2—C14—N3−0.5 (2)C6—C7—C8—C90.8 (2)
C14—N3—C13—C12−0.3 (2)C15—C7—C8—N10.6 (2)
C13—N3—C14—N20.6 (3)C15—C7—C8—C9−179.20 (13)
Cl1—C1—C2—C3178.55 (10)N1—C8—C9—C3−0.48 (19)
Cl1—C1—C2—C10−1.18 (17)N1—C8—C9—C4179.12 (12)
N1—C1—C2—C3−1.2 (2)C7—C8—C9—C3179.36 (12)
N1—C1—C2—C10179.08 (13)C7—C8—C9—C4−1.0 (2)
C1—C2—C3—C9−0.14 (19)O1—C11—C12—C13−178.79 (14)
C10—C2—C3—C9179.58 (12)N2—C11—C12—C130.3 (2)
C1—C2—C10—O1178.90 (11)C11—C12—C13—N3−0.1 (3)
C3—C2—C10—O1−0.80 (18)

Symmetry codes: (i) −x+3/2, y−1/2, −z−1/2; (ii) −x+1/2, y+1/2, −z−1/2; (iii) x−1/2, −y+1/2, z−1/2; (iv) x−1, y−1, z; (v) −x+1, −y, −z; (vi) −x+1, −y+1, −z; (vii) −x+3/2, y+1/2, −z−1/2; (viii) −x+3/2, y−1/2, −z+1/2; (ix) x+1/2, −y+1/2, z+1/2; (x) −x+3/2, y+1/2, −z+1/2; (xi) −x+1/2, y−1/2, −z−1/2; (xii) x+1, y+1, z.

Hydrogen-bond geometry (Å, °)

Cg3 is the centroid of the C4–C9 ring.
D—H···AD—HH···AD···AD—H···A
C3—H3···O10.932.362.7056 (17)102
C10—H10A···Cg3vi0.972.723.5132 (15)140

Symmetry codes: (vi) −x+1, −y+1, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FJ2289).

References

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