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

Ling, Z.; Shi, D.; Yanqiu, F.; Wei, X.; Li, J.

doi:10.1107/S1600536809014111

organic compounds

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ISSN: 2056-9890

Volume 65| Part 5| May 2009| Page o1097

doi:10.1107/S1600536809014111

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

Zhang Ling,^a Daxin Shi,^a Fan Yanqiu,^a Xia Wei ^a and Jiarong Li ^a ^*

^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 ); Shi et al. (2003 , 2004 ).

Experimental

Crystal data

C₁₄H₁₈N₂O
M_r = 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 ) 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[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
Δρ_max = 0.30 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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); cell refinement: CrystalClear; data reduction: CrystalClear; 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809014111/ya2085sup1.cif

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

checkCIF report

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.

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

	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.

6'-Methyl-1',2',3',4'-tetrahydrospirocyclohexane-2'-quinazolin-4'-one top

Crystal data top

C₁₄H₁₈N₂O	F(000) = 496
M_r = 230.30	D_x = 1.292 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3810 reflections
a = 9.4077 (19) Å	θ = 1.7–27.9°
b = 11.853 (2) Å	µ = 0.08 mm⁻¹
c = 11.067 (2) Å	T = 113 K
β = 106.44 (3)°	Cube, colorless
V = 1183.6 (4) Å³	0.28 × 0.24 × 0.20 mm
Z = 4

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2810 independent reflections
Radiation source: rotating anode	2346 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.034
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 2.5°
ω and ϕ scans	h = −12→12
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −15→15
T_min = 0.977, T_max = 0.984	l = −14→14
14356 measured reflections

Refinement top

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.109	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ²(F_o²) + (0.0601P)² + 0.2329P] where P = (F_o² + 2F_c²)/3
2810 reflections	(Δ/σ)_max = 0.003
163 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₄H₁₈N₂O	V = 1183.6 (4) Å³
M_r = 230.30	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 9.4077 (19) Å	µ = 0.08 mm⁻¹
b = 11.853 (2) Å	T = 113 K
c = 11.067 (2) Å	0.28 × 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)
T_min = 0.977, T_max = 0.984	R_int = 0.034
14356 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.109	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	Δρ_max = 0.30 e Å⁻³
2810 reflections	Δρ_min = −0.26 e Å⁻³
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

	x	y	z	U_iso*/U_eq
O1	0.01942 (8)	0.42294 (7)	0.36579 (7)	0.0182 (2)
N1	0.32706 (11)	0.24403 (8)	0.61566 (9)	0.0167 (2)
N2	0.16255 (10)	0.39739 (8)	0.56703 (8)	0.0144 (2)
C1	0.31997 (12)	0.22860 (9)	0.49040 (10)	0.0153 (2)
C2	0.39770 (12)	0.14331 (9)	0.44884 (11)	0.0191 (2)
H2	0.4588	0.0928	0.5078	0.023*
C3	0.38557 (12)	0.13253 (9)	0.32154 (11)	0.0197 (2)
H3	0.4379	0.0736	0.2946	0.024*
C4	0.29853 (12)	0.20585 (9)	0.23162 (10)	0.0180 (2)
C5	0.21867 (12)	0.28808 (9)	0.27333 (10)	0.0163 (2)
H5	0.1573	0.3381	0.2139	0.020*
C6	0.22636 (11)	0.29905 (9)	0.40055 (10)	0.0143 (2)
C7	0.12913 (11)	0.37917 (9)	0.44220 (10)	0.0141 (2)
C8	0.29082 (14)	0.19553 (11)	0.09415 (11)	0.0268 (3)
H8A	0.2017	0.2339	0.0431	0.040*
H8B	0.2869	0.1156	0.0707	0.040*
H8C	0.3789	0.2304	0.0793	0.040*
C9	0.30268 (11)	0.35816 (9)	0.65516 (9)	0.0142 (2)
C10	0.28781 (13)	0.35125 (9)	0.78910 (10)	0.0176 (2)
H10A	0.1961	0.3095	0.7872	0.021*
H10B	0.3726	0.3080	0.8423	0.021*
C11	0.28289 (12)	0.46671 (10)	0.84905 (10)	0.0192 (2)
H11A	0.2840	0.4566	0.9381	0.023*
H11B	0.1895	0.5055	0.8046	0.023*
C12	0.41467 (13)	0.53975 (10)	0.84304 (10)	0.0215 (3)
H12A	0.4071	0.6148	0.8799	0.026*
H12B	0.5081	0.5040	0.8927	0.026*
C13	0.41659 (13)	0.55324 (10)	0.70664 (10)	0.0204 (3)
H13A	0.5013	0.6013	0.7029	0.024*
H13B	0.3242	0.5906	0.6574	0.024*
C14	0.43013 (12)	0.43771 (9)	0.64986 (10)	0.0169 (2)
H14A	0.5257	0.4030	0.6963	0.020*
H14B	0.4303	0.4474	0.5610	0.020*
H2A	0.1067 (16)	0.4493 (13)	0.5919 (13)	0.027 (4)*
H1	0.3942 (18)	0.2055 (13)	0.6744 (14)	0.031 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0160 (4)	0.0208 (4)	0.0164 (4)	0.0053 (3)	0.0024 (3)	0.0005 (3)
N1	0.0198 (5)	0.0136 (5)	0.0159 (5)	0.0048 (4)	0.0040 (4)	0.0011 (3)
N2	0.0131 (4)	0.0143 (4)	0.0157 (4)	0.0030 (3)	0.0039 (3)	−0.0006 (3)
C1	0.0143 (5)	0.0135 (5)	0.0181 (5)	−0.0014 (4)	0.0048 (4)	−0.0013 (4)
C2	0.0187 (5)	0.0154 (5)	0.0226 (6)	0.0040 (4)	0.0045 (4)	−0.0011 (4)
C3	0.0175 (5)	0.0178 (5)	0.0247 (6)	0.0007 (4)	0.0073 (4)	−0.0065 (4)
C4	0.0153 (5)	0.0199 (6)	0.0192 (5)	−0.0034 (4)	0.0058 (4)	−0.0052 (4)
C5	0.0135 (5)	0.0171 (5)	0.0176 (5)	−0.0014 (4)	0.0034 (4)	−0.0018 (4)
C6	0.0124 (5)	0.0126 (5)	0.0178 (5)	−0.0014 (4)	0.0042 (4)	−0.0015 (4)
C7	0.0124 (5)	0.0128 (5)	0.0172 (5)	−0.0012 (4)	0.0045 (4)	0.0005 (4)
C8	0.0291 (6)	0.0327 (7)	0.0198 (6)	0.0046 (5)	0.0090 (5)	−0.0052 (5)
C9	0.0140 (5)	0.0135 (5)	0.0142 (5)	0.0020 (4)	0.0027 (4)	−0.0001 (4)
C10	0.0207 (5)	0.0178 (5)	0.0148 (5)	0.0019 (4)	0.0056 (4)	0.0020 (4)
C11	0.0196 (5)	0.0226 (6)	0.0144 (5)	0.0036 (4)	0.0031 (4)	−0.0017 (4)
C12	0.0196 (6)	0.0231 (6)	0.0186 (5)	0.0002 (5)	0.0004 (4)	−0.0059 (4)
C13	0.0196 (5)	0.0175 (6)	0.0224 (6)	−0.0032 (4)	0.0033 (4)	−0.0012 (4)
C14	0.0140 (5)	0.0183 (5)	0.0180 (5)	−0.0009 (4)	0.0042 (4)	−0.0003 (4)

Geometric parameters (Å, º) top

O1—C7	1.2472 (13)	C8—H8B	0.9800
N1—C1	1.3810 (14)	C8—H8C	0.9800
N1—C9	1.4596 (14)	C9—C10	1.5299 (14)
N1—H1	0.893 (16)	C9—C14	1.5394 (15)
N2—C7	1.3446 (13)	C10—C11	1.5273 (16)
N2—C9	1.4757 (14)	C10—H10A	0.9900
N2—H2A	0.901 (16)	C10—H10B	0.9900
C1—C2	1.3995 (15)	C11—C12	1.5289 (16)
C1—C6	1.4022 (15)	C11—H11A	0.9900
C2—C3	1.3867 (15)	C11—H11B	0.9900
C2—H2	0.9500	C12—C13	1.5232 (16)
C3—C4	1.3982 (17)	C12—H12A	0.9900
C3—H3	0.9500	C12—H12B	0.9900
C4—C5	1.3870 (15)	C13—C14	1.5269 (15)
C4—C8	1.5074 (15)	C13—H13A	0.9900
C5—C6	1.3953 (14)	C13—H13B	0.9900
C5—H5	0.9500	C14—H14A	0.9900
C6—C7	1.4797 (14)	C14—H14B	0.9900
C8—H8A	0.9800

C1—N1—C9	117.15 (9)	N2—C9—C10	110.35 (9)
C1—N1—H1	119.1 (10)	N1—C9—C14	111.48 (9)
C9—N1—H1	113.2 (10)	N2—C9—C14	109.97 (8)
C7—N2—C9	122.26 (9)	C10—C9—C14	110.82 (9)
C7—N2—H2A	115.9 (9)	C11—C10—C9	113.28 (9)
C9—N2—H2A	120.1 (9)	C11—C10—H10A	108.9
N1—C1—C2	122.97 (10)	C9—C10—H10A	108.9
N1—C1—C6	118.37 (10)	C11—C10—H10B	108.9
C2—C1—C6	118.61 (10)	C9—C10—H10B	108.9
C3—C2—C1	120.00 (10)	H10A—C10—H10B	107.7
C3—C2—H2	120.0	C10—C11—C12	111.34 (9)
C1—C2—H2	120.0	C10—C11—H11A	109.4
C2—C3—C4	121.94 (10)	C12—C11—H11A	109.4
C2—C3—H3	119.0	C10—C11—H11B	109.4
C4—C3—H3	119.0	C12—C11—H11B	109.4
C5—C4—C3	117.59 (10)	H11A—C11—H11B	108.0
C5—C4—C8	121.13 (10)	C13—C12—C11	109.86 (9)
C3—C4—C8	121.28 (10)	C13—C12—H12A	109.7
C4—C5—C6	121.54 (10)	C11—C12—H12A	109.7
C4—C5—H5	119.2	C13—C12—H12B	109.7
C6—C5—H5	119.2	C11—C12—H12B	109.7
C5—C6—C1	120.19 (10)	H12A—C12—H12B	108.2
C5—C6—C7	120.94 (9)	C12—C13—C14	109.84 (9)
C1—C6—C7	118.74 (9)	C12—C13—H13A	109.7
O1—C7—N2	122.54 (10)	C14—C13—H13A	109.7
O1—C7—C6	121.44 (9)	C12—C13—H13B	109.7
N2—C7—C6	115.95 (9)	C14—C13—H13B	109.7
C4—C8—H8A	109.5	H13A—C13—H13B	108.2
C4—C8—H8B	109.5	C13—C14—C9	112.16 (9)
H8A—C8—H8B	109.5	C13—C14—H14A	109.2
C4—C8—H8C	109.5	C9—C14—H14A	109.2
H8A—C8—H8C	109.5	C13—C14—H14B	109.2
H8B—C8—H8C	109.5	C9—C14—H14B	109.2
N1—C9—N2	106.31 (8)	H14A—C14—H14B	107.9
N1—C9—C10	107.80 (8)

C9—N1—C1—C2	152.24 (10)	C5—C6—C7—N2	−168.95 (9)
C9—N1—C1—C6	−30.19 (14)	C1—C6—C7—N2	15.21 (14)
N1—C1—C2—C3	179.98 (10)	C1—N1—C9—N2	51.63 (12)
C6—C1—C2—C3	2.41 (16)	C1—N1—C9—C10	169.95 (9)
C1—C2—C3—C4	0.84 (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—C8	177.80 (11)	C7—N2—C9—C10	−159.42 (9)
C3—C4—C5—C6	1.10 (16)	C7—N2—C9—C14	78.03 (12)
C8—C4—C5—C6	−179.30 (10)	N1—C9—C10—C11	172.15 (9)
C4—C5—C6—C1	2.13 (16)	N2—C9—C10—C11	−72.16 (11)
C4—C5—C6—C7	−173.64 (10)	C14—C9—C10—C11	49.90 (12)
N1—C1—C6—C5	178.45 (9)	C9—C10—C11—C12	−53.09 (12)
C2—C1—C6—C5	−3.87 (16)	C10—C11—C12—C13	57.52 (12)
N1—C1—C6—C7	−5.69 (15)	C11—C12—C13—C14	−60.01 (12)
C2—C1—C6—C7	171.99 (9)	C12—C13—C14—C9	58.30 (12)
C9—N2—C7—O1	−171.57 (10)	N1—C9—C14—C13	−172.67 (8)
C9—N2—C7—C6	11.38 (14)	N2—C9—C14—C13	69.67 (11)
C5—C6—C7—O1	13.96 (15)	C10—C9—C14—C13	−52.60 (11)
C1—C6—C7—O1	−161.87 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₈N₂O
M_r	230.30
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	113
a, b, c (Å)	9.4077 (19), 11.853 (2), 11.067 (2)
β (°)	106.44 (3)
V (Å³)	1183.6 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.28 × 0.24 × 0.20

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.977, 0.984
No. of measured, independent and observed [I > 2σ(I)] reflections	14356, 2810, 2346
R_int	0.034
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.109, 1.09
No. of reflections	2810
No. of parameters	163
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	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···A	D—H	H···A	D···A	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.

Acknowledgements

The authors thank Beijing Institute of Technology for financial support.

References

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