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Acta Crystallogr Sect E Struct Rep Online. 2009 May 1; 65(Pt 5): o1097.
Published online 2009 April 22. doi:  10.1107/S1600536809014111
PMCID: PMC2977775

6′-Methyl-1′,2′,3′,4′-tetra­hydro­spiro­cyclo­hexane-2′-quinazolin-4′-one

Abstract

The title compound, C14H18N2O, was synthesized by the reaction of cyclo­hexa­none and 2-amino-5-methyl­benzonitrile. In the mol­ecule, the cyclo­hexane ring displays a chair conformation, whereas the 1,3-diaza­cyclo­hexane moiety of the bicyclic system has a sofa conformation with the spiro C atom displaced by 0.603 (2) Å from the rest of the atoms of the 1,3-diaza­cyclo­hexane ring [planar within 0.052 (2) Å]. Mol­ecules are linked into centrosymmetric dimers via N—H(...)O hydrogen bonds.

Related literature

For medicinal and biological properties of dihydro­quinazolin-4(3H)-one derivatives, see: Jackson et al. (2007 [triangle]); Shi et al. (2003 [triangle], 2004 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1097-scheme1.jpg

Experimental

Crystal data

  • C14H18N2O
  • M r = 230.30
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1097-efi1.jpg
  • a = 9.4077 (19) Å
  • b = 11.853 (2) Å
  • c = 11.067 (2) Å
  • β = 106.44 (3)°
  • V = 1183.6 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 113 K
  • 0.28 × 0.24 × 0.20 mm

Data collection

  • Rigaku Saturn CCD area-detector diffractometer
  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 [triangle]) T min = 0.977, T max = 0.984
  • 14356 measured reflections
  • 2810 independent reflections
  • 2346 reflections with I > 2σ(I)
  • R int = 0.034

Refinement

  • R[F 2 > 2σ(F 2)] = 0.039
  • wR(F 2) = 0.109
  • S = 1.09
  • 2810 reflections
  • 163 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.30 e Å−3
  • Δρmin = −0.26 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2005 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; 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/S1600536809014111/ya2085sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809014111/ya2085Isup2.hkl

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

Acknowledgments

The authors thank Beijing Institute of Technology for financial support.

supplementary crystallographic information

Comment

Derivatives of dihydroquinazolin-4(3H)-one are valuable synthetic intermediates featuring common structural motif found in a variety of compounds with interesting medicinal and biological properties (Shi et al., 2004; Jackson et al., 2007).

In the molecule of the title compound (Fig. 1) the cyclohexane ring displays a regular chair conformation, whereas, the 1,3-diazacyclohexane moiety of the bicyclic system has a sofa conformation with the C9 atom displaced by 0.603 (2) Å from the rest of the atoms of the 1,3-diazacyclohexane ring (planar within 0.052 (2) Å).

Molecules in crystal are linked into centrosymmetric dimers via N2—H2A···O1i [symmetry code (i): -x, 1 - y, 1 - z] bond (Fig. 2).

The molecular geometry and overall crystal structure of the title compound are quite similar to those observed in the structure of its close analog which lacks the methyl substituent in position 6 of the tetrahydroquinazolinone system (Shi et al., 2003).

Experimental

A solution of 2-amino-5-methylbenzonitrile (10 mmol) and zinc chloride (10 mmol) in cyclohexanone (2 ml) was refluxed for 2 h. The reaction mixture was cooled to room temperature and poured into 20 ml of water (previously cooled to 20°); it was then filtered in vacuo to give the title compound. The product was recrystallizated from ethanol to give colorless crystalline powder. m.p. 527–528 K; IR (KBr): 3367 (N—H), 3028, 2936 (C—H), 1648 (C=O) cm-1; 1H-NMR(DMSO, p.p.m.): 1.25–1.78 (10H, m), 2.35(3H, s) 6.63 (1H, m), 6.87 (1H, d), 6.91 (1H, s), 7.55 (1H, d), 8.06(1H, s). 50 mg of the obtained product was dissolved in ethyl acetate (5 ml) and the solution was kept at room temperature for 4 days to give colorless single crystals.

Refinement

The H atoms bonded to C were included in the riding model approximation with C—H distances 0.95–0.99 Å, and with Uiso=1.2Ueq or 1.5Ueq (for methyl H atoms). The H atoms bonded to N were located in the difference Fourier map and refined isotropically [N1—H1 0.89 (2); N2—H2A 0.90 (2)].

Figures

Fig. 1.
Molecular structure of the title compound with thermal displacement ellipsoids drawn at the 50% probability level; the H atoms are represented as small circles of arbitrary radius.
Fig. 2.
The crystal packing of the title compound, viewed down the b axis; H-bonds are shown as dashed lines.

Crystal data

C14H18N2OF(000) = 496
Mr = 230.30Dx = 1.292 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 3810 reflections
a = 9.4077 (19) Åθ = 1.7–27.9°
b = 11.853 (2) ŵ = 0.08 mm1
c = 11.067 (2) ÅT = 113 K
β = 106.44 (3)°Cube, colorless
V = 1183.6 (4) Å30.28 × 0.24 × 0.20 mm
Z = 4

Data collection

Rigaku Saturn CCD area-detector diffractometer2810 independent reflections
Radiation source: rotating anode2346 reflections with I > 2σ(I)
confocalRint = 0.034
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 2.5°
ω and [var phi] scansh = −12→12
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −15→15
Tmin = 0.977, Tmax = 0.984l = −14→14
14356 measured reflections

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)] = 0.039Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.109H atoms treated by a mixture of independent and constrained refinement
S = 1.09w = 1/[σ2(Fo2) + (0.0601P)2 + 0.2329P] where P = (Fo2 + 2Fc2)/3
2810 reflections(Δ/σ)max = 0.003
163 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = −0.26 e Å3

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 (Å2)

xyzUiso*/Ueq
O10.01942 (8)0.42294 (7)0.36579 (7)0.0182 (2)
N10.32706 (11)0.24403 (8)0.61566 (9)0.0167 (2)
N20.16255 (10)0.39739 (8)0.56703 (8)0.0144 (2)
C10.31997 (12)0.22860 (9)0.49040 (10)0.0153 (2)
C20.39770 (12)0.14331 (9)0.44884 (11)0.0191 (2)
H20.45880.09280.50780.023*
C30.38557 (12)0.13253 (9)0.32154 (11)0.0197 (2)
H30.43790.07360.29460.024*
C40.29853 (12)0.20585 (9)0.23162 (10)0.0180 (2)
C50.21867 (12)0.28808 (9)0.27333 (10)0.0163 (2)
H50.15730.33810.21390.020*
C60.22636 (11)0.29905 (9)0.40055 (10)0.0143 (2)
C70.12913 (11)0.37917 (9)0.44220 (10)0.0141 (2)
C80.29082 (14)0.19553 (11)0.09415 (11)0.0268 (3)
H8A0.20170.23390.04310.040*
H8B0.28690.11560.07070.040*
H8C0.37890.23040.07930.040*
C90.30268 (11)0.35816 (9)0.65516 (9)0.0142 (2)
C100.28781 (13)0.35125 (9)0.78910 (10)0.0176 (2)
H10A0.19610.30950.78720.021*
H10B0.37260.30800.84230.021*
C110.28289 (12)0.46671 (10)0.84905 (10)0.0192 (2)
H11A0.28400.45660.93810.023*
H11B0.18950.50550.80460.023*
C120.41467 (13)0.53975 (10)0.84304 (10)0.0215 (3)
H12A0.40710.61480.87990.026*
H12B0.50810.50400.89270.026*
C130.41659 (13)0.55324 (10)0.70664 (10)0.0204 (3)
H13A0.50130.60130.70290.024*
H13B0.32420.59060.65740.024*
C140.43013 (12)0.43771 (9)0.64986 (10)0.0169 (2)
H14A0.52570.40300.69630.020*
H14B0.43030.44740.56100.020*
H2A0.1067 (16)0.4493 (13)0.5919 (13)0.027 (4)*
H10.3942 (18)0.2055 (13)0.6744 (14)0.031 (4)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0160 (4)0.0208 (4)0.0164 (4)0.0053 (3)0.0024 (3)0.0005 (3)
N10.0198 (5)0.0136 (5)0.0159 (5)0.0048 (4)0.0040 (4)0.0011 (3)
N20.0131 (4)0.0143 (4)0.0157 (4)0.0030 (3)0.0039 (3)−0.0006 (3)
C10.0143 (5)0.0135 (5)0.0181 (5)−0.0014 (4)0.0048 (4)−0.0013 (4)
C20.0187 (5)0.0154 (5)0.0226 (6)0.0040 (4)0.0045 (4)−0.0011 (4)
C30.0175 (5)0.0178 (5)0.0247 (6)0.0007 (4)0.0073 (4)−0.0065 (4)
C40.0153 (5)0.0199 (6)0.0192 (5)−0.0034 (4)0.0058 (4)−0.0052 (4)
C50.0135 (5)0.0171 (5)0.0176 (5)−0.0014 (4)0.0034 (4)−0.0018 (4)
C60.0124 (5)0.0126 (5)0.0178 (5)−0.0014 (4)0.0042 (4)−0.0015 (4)
C70.0124 (5)0.0128 (5)0.0172 (5)−0.0012 (4)0.0045 (4)0.0005 (4)
C80.0291 (6)0.0327 (7)0.0198 (6)0.0046 (5)0.0090 (5)−0.0052 (5)
C90.0140 (5)0.0135 (5)0.0142 (5)0.0020 (4)0.0027 (4)−0.0001 (4)
C100.0207 (5)0.0178 (5)0.0148 (5)0.0019 (4)0.0056 (4)0.0020 (4)
C110.0196 (5)0.0226 (6)0.0144 (5)0.0036 (4)0.0031 (4)−0.0017 (4)
C120.0196 (6)0.0231 (6)0.0186 (5)0.0002 (5)0.0004 (4)−0.0059 (4)
C130.0196 (5)0.0175 (6)0.0224 (6)−0.0032 (4)0.0033 (4)−0.0012 (4)
C140.0140 (5)0.0183 (5)0.0180 (5)−0.0009 (4)0.0042 (4)−0.0003 (4)

Geometric parameters (Å, °)

O1—C71.2472 (13)C8—H8B0.9800
N1—C11.3810 (14)C8—H8C0.9800
N1—C91.4596 (14)C9—C101.5299 (14)
N1—H10.893 (16)C9—C141.5394 (15)
N2—C71.3446 (13)C10—C111.5273 (16)
N2—C91.4757 (14)C10—H10A0.9900
N2—H2A0.901 (16)C10—H10B0.9900
C1—C21.3995 (15)C11—C121.5289 (16)
C1—C61.4022 (15)C11—H11A0.9900
C2—C31.3867 (15)C11—H11B0.9900
C2—H20.9500C12—C131.5232 (16)
C3—C41.3982 (17)C12—H12A0.9900
C3—H30.9500C12—H12B0.9900
C4—C51.3870 (15)C13—C141.5269 (15)
C4—C81.5074 (15)C13—H13A0.9900
C5—C61.3953 (14)C13—H13B0.9900
C5—H50.9500C14—H14A0.9900
C6—C71.4797 (14)C14—H14B0.9900
C8—H8A0.9800
C1—N1—C9117.15 (9)N2—C9—C10110.35 (9)
C1—N1—H1119.1 (10)N1—C9—C14111.48 (9)
C9—N1—H1113.2 (10)N2—C9—C14109.97 (8)
C7—N2—C9122.26 (9)C10—C9—C14110.82 (9)
C7—N2—H2A115.9 (9)C11—C10—C9113.28 (9)
C9—N2—H2A120.1 (9)C11—C10—H10A108.9
N1—C1—C2122.97 (10)C9—C10—H10A108.9
N1—C1—C6118.37 (10)C11—C10—H10B108.9
C2—C1—C6118.61 (10)C9—C10—H10B108.9
C3—C2—C1120.00 (10)H10A—C10—H10B107.7
C3—C2—H2120.0C10—C11—C12111.34 (9)
C1—C2—H2120.0C10—C11—H11A109.4
C2—C3—C4121.94 (10)C12—C11—H11A109.4
C2—C3—H3119.0C10—C11—H11B109.4
C4—C3—H3119.0C12—C11—H11B109.4
C5—C4—C3117.59 (10)H11A—C11—H11B108.0
C5—C4—C8121.13 (10)C13—C12—C11109.86 (9)
C3—C4—C8121.28 (10)C13—C12—H12A109.7
C4—C5—C6121.54 (10)C11—C12—H12A109.7
C4—C5—H5119.2C13—C12—H12B109.7
C6—C5—H5119.2C11—C12—H12B109.7
C5—C6—C1120.19 (10)H12A—C12—H12B108.2
C5—C6—C7120.94 (9)C12—C13—C14109.84 (9)
C1—C6—C7118.74 (9)C12—C13—H13A109.7
O1—C7—N2122.54 (10)C14—C13—H13A109.7
O1—C7—C6121.44 (9)C12—C13—H13B109.7
N2—C7—C6115.95 (9)C14—C13—H13B109.7
C4—C8—H8A109.5H13A—C13—H13B108.2
C4—C8—H8B109.5C13—C14—C9112.16 (9)
H8A—C8—H8B109.5C13—C14—H14A109.2
C4—C8—H8C109.5C9—C14—H14A109.2
H8A—C8—H8C109.5C13—C14—H14B109.2
H8B—C8—H8C109.5C9—C14—H14B109.2
N1—C9—N2106.31 (8)H14A—C14—H14B107.9
N1—C9—C10107.80 (8)
C9—N1—C1—C2152.24 (10)C5—C6—C7—N2−168.95 (9)
C9—N1—C1—C6−30.19 (14)C1—C6—C7—N215.21 (14)
N1—C1—C2—C3179.98 (10)C1—N1—C9—N251.63 (12)
C6—C1—C2—C32.41 (16)C1—N1—C9—C10169.95 (9)
C1—C2—C3—C40.84 (17)C1—N1—C9—C14−68.21 (12)
C2—C3—C4—C5−2.60 (16)C7—N2—C9—N1−42.79 (13)
C2—C3—C4—C8177.80 (11)C7—N2—C9—C10−159.42 (9)
C3—C4—C5—C61.10 (16)C7—N2—C9—C1478.03 (12)
C8—C4—C5—C6−179.30 (10)N1—C9—C10—C11172.15 (9)
C4—C5—C6—C12.13 (16)N2—C9—C10—C11−72.16 (11)
C4—C5—C6—C7−173.64 (10)C14—C9—C10—C1149.90 (12)
N1—C1—C6—C5178.45 (9)C9—C10—C11—C12−53.09 (12)
C2—C1—C6—C5−3.87 (16)C10—C11—C12—C1357.52 (12)
N1—C1—C6—C7−5.69 (15)C11—C12—C13—C14−60.01 (12)
C2—C1—C6—C7171.99 (9)C12—C13—C14—C958.30 (12)
C9—N2—C7—O1−171.57 (10)N1—C9—C14—C13−172.67 (8)
C9—N2—C7—C611.38 (14)N2—C9—C14—C1369.67 (11)
C5—C6—C7—O113.96 (15)C10—C9—C14—C13−52.60 (11)
C1—C6—C7—O1−161.87 (10)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2A···O1i0.901 (16)2.058 (16)2.9563 (13)174.5 (13)

Symmetry codes: (i) −x, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: YA2085).

References

  • Jackson, J. R., Patrick, D. R., Dar, M. M. & Huang, P. S. (2007). Nat. Rev. Cancer, 7, 107–117. [PubMed]
  • Rigaku/MSC (2005). CrystalClear Rigaku/MSC Inc., The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Shi, D. Q., Rong, L. C., Wang, J. X., Wang, X. S., Tu, S. J. & Hu, H. W. (2004). Chem. J. Chin. Univ.25, 2051–2053.
  • Shi, D. Q., Rong, L., Wang, J., Zhuang, Q., Wang, X. & Hu, H. (2003). Tetrahedron Lett.44, 3199–3201.

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