organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890
Volume 65| Part 5| May 2009| Page o1097

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

aSchool of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, People's Republic of China
*Correspondence e-mail: jrli@bit.edu.cn

(Received 15 January 2009; accepted 15 April 2009; online 22 April 2009)

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[Jackson, J. R., Patrick, D. R., Dar, M. M. & Huang, P. S. (2007). Nat. Rev. Cancer, 7, 107-117.]); Shi et al. (2003[Shi, D. Q., Rong, L., Wang, J., Zhuang, Q., Wang, X. & Hu, H. (2003). Tetrahedron Lett. 44, 3199-3201.], 2004[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.]).

[Scheme 1]

Experimental

Crystal data
  • C14H18N2O

  • Mr = 230.30

  • Monoclinic, P 21 /n

  • 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[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]) Tmin = 0.977, Tmax = 0.984

  • 14356 measured reflections

  • 2810 independent reflections

  • 2346 reflections with I > 2σ(I)

  • Rint = 0.034

Refinement
  • R[F2 > 2σ(F2)] = 0.039

  • wR(F2) = 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

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2A⋯O1i 0.901 (16) 2.058 (16) 2.9563 (13) 174.5 (13)
Symmetry code: (i) -x, -y+1, -z+1.

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

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).

Related literature top

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

Experimental top

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 top

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)].

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (Rigaku/MSC, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] 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.
[Figure 2] Fig. 2. The crystal packing of the title compound, viewed down the b axis; H-bonds are shown as dashed lines.
6'-Methyl-1',2',3',4'-tetrahydrospirocyclohexane-2'-quinazolin-4'-one top
Crystal data top
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 top
Rigaku Saturn CCD area-detector
diffractometer
2810 independent reflections
Radiation source: rotating anode2346 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.034
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 2.5°
ω and ϕ scansh = 1212
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
k = 1515
Tmin = 0.977, Tmax = 0.984l = 1414
14356 measured reflections
Refinement top
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 = 1.09 w = 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
Crystal data top
C14H18N2OV = 1183.6 (4) Å3
Mr = 230.30Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.4077 (19) ŵ = 0.08 mm1
b = 11.853 (2) ÅT = 113 K
c = 11.067 (2) Å0.28 × 0.24 × 0.20 mm
β = 106.44 (3)°
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
2810 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
2346 reflections with I > 2σ(I)
Tmin = 0.977, Tmax = 0.984Rint = 0.034
14356 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0390 restraints
wR(F2) = 0.109H atoms treated by a mixture of independent and constrained refinement
S = 1.09Δρmax = 0.30 e Å3
2810 reflectionsΔρmin = 0.26 e Å3
163 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
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) top
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, º) top
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—N2168.95 (9)
C9—N1—C1—C630.19 (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—C1468.21 (12)
C2—C3—C4—C52.60 (16)C7—N2—C9—N142.79 (13)
C2—C3—C4—C8177.80 (11)C7—N2—C9—C10159.42 (9)
C3—C4—C5—C61.10 (16)C7—N2—C9—C1478.03 (12)
C8—C4—C5—C6179.30 (10)N1—C9—C10—C11172.15 (9)
C4—C5—C6—C12.13 (16)N2—C9—C10—C1172.16 (11)
C4—C5—C6—C7173.64 (10)C14—C9—C10—C1149.90 (12)
N1—C1—C6—C5178.45 (9)C9—C10—C11—C1253.09 (12)
C2—C1—C6—C53.87 (16)C10—C11—C12—C1357.52 (12)
N1—C1—C6—C75.69 (15)C11—C12—C13—C1460.01 (12)
C2—C1—C6—C7171.99 (9)C12—C13—C14—C958.30 (12)
C9—N2—C7—O1171.57 (10)N1—C9—C14—C13172.67 (8)
C9—N2—C7—C611.38 (14)N2—C9—C14—C1369.67 (11)
C5—C6—C7—O113.96 (15)C10—C9—C14—C1352.60 (11)
C1—C6—C7—O1161.87 (10)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O1i0.901 (16)2.058 (16)2.9563 (13)174.5 (13)
Symmetry code: (i) x, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC14H18N2O
Mr230.30
Crystal system, space groupMonoclinic, P21/n
Temperature (K)113
a, b, c (Å)9.4077 (19), 11.853 (2), 11.067 (2)
β (°) 106.44 (3)
V3)1183.6 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.08
Crystal size (mm)0.28 × 0.24 × 0.20
Data collection
DiffractometerRigaku Saturn CCD area-detector
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku/MSC, 2005)
Tmin, Tmax0.977, 0.984
No. of measured, independent and
observed [I > 2σ(I)] reflections
14356, 2810, 2346
Rint0.034
(sin θ/λ)max1)0.658
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.109, 1.09
No. of reflections2810
No. of parameters163
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.30, 0.26

Computer programs: CrystalClear (Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O1i0.901 (16)2.058 (16)2.9563 (13)174.5 (13)
Symmetry code: (i) x, y+1, z+1.
 

Acknowledgements

The authors thank Beijing Institute of Technology for financial support.

References

First citationJackson, J. R., Patrick, D. R., Dar, M. M. & Huang, P. S. (2007). Nat. Rev. Cancer, 7, 107–117.  Web of Science CrossRef PubMed CAS Google Scholar
First citationRigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationShi, 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.  CAS Google Scholar
First citationShi, D. Q., Rong, L., Wang, J., Zhuang, Q., Wang, X. & Hu, H. (2003). Tetrahedron Lett. 44, 3199–3201.  Web of Science CSD CrossRef CAS Google Scholar

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Journal logoCRYSTALLOGRAPHIC
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ISSN: 2056-9890
Volume 65| Part 5| May 2009| Page o1097
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