3-(2-Amino­ethyl)-2-(4-chloro­anilino)­quinazolin-4(3H)-one methanol 0.75-solvate

Xu-Hong Yang; Xiao-Bao Chen; Si-Xuan Zhou

doi:10.1107/S160053680804049X

. 2008 Dec 7;65(Pt 1):o185–o186. doi: 10.1107/S160053680804049X

3-(2-Aminoethyl)-2-(4-chloroanilino)quinazolin-4(3H)-one methanol 0.75-solvate

Xu-Hong Yang ^a,^*, Xiao-Bao Chen ^b, Si-Xuan Zhou ^c

PMCID: PMC2968094 PMID: 21581640

Abstract

In the asymmetric unit of the title compound, C₁₆H₁₅ClN₄O·0.75CH₃OH, there are two independent quinazolin-4(3H)-one molecules and one and a half methanol molecules. One of the methanol molecules is disordered over two positions with equal occupancies. The dihedral angles between the quinazoline ring system and the chlorobenzene ring in the two quinazolin-4(3H)-one molecules are essentially the same, at 39.83 (1) and 39.84 (1)°. Intramolecular N—H⋯N and O—H⋯O, and intermolecular N—H⋯O and N—H⋯N hydrogen bonds are observed. In addition, π–π stacking interactions, with centroid-to-centroid distances of 3.654 (1), 3.766 (1) and 3.767 (1) Å, and weak C—H⋯π interactions, are observed.

Related literature

For the biological activity of quinazoline-4(3H)-one derivatives, see: Bartroli et al. (1998 ▶); Kung et al. (1999 ▶); Malamas & Millen (1991 ▶); Mannschreck et al. (1984 ▶); Matsuno et al. (2002 ▶); Palmer et al. (1997 ▶); Pandeya et al. (1999 ▶); Shiba et al. (1997 ▶); Tsou et al. (2001 ▶). For the synthesis of the title compound, see: Hu et al. (2006 ▶); Yang et al. (2008 ▶).

Experimental

Crystal data

C₁₆H₁₅ClN₄O·0.75CH₄O
M _r = 338.81
Monoclinic,
a = 13.380 (3) Å
b = 12.048 (2) Å
c = 21.105 (4) Å
β = 104.49 (3)°
V = 3293.8 (11) Å³
Z = 8
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 293 (2) K
0.23 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: none
18726 measured reflections
6451 independent reflections
4529 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.132
S = 1.07
6451 reflections
453 parameters
9 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.40 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; 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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680804049X/is2361sup1.cif

e-65-0o185-sup1.cif^{(29.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680804049X/is2361Isup2.hkl

e-65-0o185-Isup2.hkl^{(315.8KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N5—H5A⋯N8	0.863 (9)	1.933 (11)	2.787 (3)	170 (2)
O4—H4C⋯O1	0.82	2.15	2.889 (6)	151
O3—H3A⋯O2	0.835 (10)	1.917 (11)	2.744 (3)	170 (2)
N1—H1A⋯N4	0.877 (9)	1.904 (11)	2.760 (3)	164 (2)
N8—H8B⋯O4ⁱ	0.851 (10)	2.467 (14)	3.284 (8)	161 (2)
N8—H8A⋯N2ⁱⁱ	0.861 (10)	2.440 (17)	3.160 (2)	142 (2)
N4—H4B⋯O3ⁱⁱⁱ	0.858 (10)	2.097 (11)	2.941 (3)	168 (2)
N4—H4A⋯N6^iv	0.853 (10)	2.491 (17)	3.223 (3)	144 (2)
C5—H5⋯Cg4^iv	0.93	2.81	3.375 (2)	120
C17—H17⋯Cg1ⁱⁱ	0.93	2.84	3.459 (2)	125
C32—H32A⋯Cg2ⁱⁱ	0.97	2.98	3.824 (3)	146

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) . Cg1, Cg2 and Cg4 are the centroids of the N2/C7/N3/C8–C10, C1–C6 and N6/C23/N7/C24–C26 rings, respectively.

Acknowledgments

The authors gratefully acknowledge financial support of this work by Xianning College, and acknowledge the Sophisticated Analytical Instrument Facility, Central China Normal University, Whuhan, for the data collection.

supplementary crystallographic information

Comment

Quinazoline-4(3H)-one derivatives have broad biological properties. Some of these activities include antimicrobial (Pandeya et al., 1999; Shiba et al., 1997), antidiabetic (Malamas & Millen, 1991), anticonvulsant (Mannschreck et al., 1984), antibacterial (Kung et al., 1999), antifungal (Bartroli et al., 1998), protein tyrosine kinase inhibitors (Palmer et al., 1997), EGFR inhibitors (Tsou et al., 2001) and PDGFR phosphorylation inhibitors (Matsuno et al., 2002). We have recently focused on the synthesis of heterocyclic compounds using an aza-Wittig reaction. We have reported the synthesis of the title compound (Yang et al., 2008). We present here the crystal structure of the title compound, (I) (Fig. 1), which can be used as a precursor for obtaining bioactive molecules.

In the crystal structure, there are two quinazolin-4(3H)-one molecules in the asymmetric unit. The quinazoline heterocycle and the adjacent chlorobenzene ring are not planar, but inclined at 39.83 (1)°. Significant intramolecular N—H···N and O—H···O and intermolecular N—H···O and N—H···N hydrogen bonds contribute strongly to the stability of the molecular configuration (Fig. 2 and Table 1). The crystal structure (Fig. 2) is stabilized by weak intermolecular C—H···π hydrogen bonds (Table 1) and by π–π stacking interactions with centroid–centroid separations of 3.654 (1), 3.767 (1) and 3.766 (1) Å for Cg1···Cg5ⁱ, Cg2···Cg6ⁱⁱ and Cg3···Cg5ⁱ, respectively, where Cg1, Cg2, Cg3, Cg5 and Cg6 are the centroids of rings N2/C7/N3/C8–C10, C1–C6, C9–C14, C17–C22 and C25–C30, respectively [symmetry codes: (i) 1/2 - x, -1/2 + y, 1/2 - z, (ii) 3/2 - x, -1/2 + y, 1/2 - z].

Experimental

The title compound was prepared according to the literature method (Hu et al., 2006; Yang et al., 2008). Single crystals suitable for X-ray diffraction were obtained from a methanol–dichloromethane (1:1 v/v) solution at room temperature.