3,3′-Bis(4-chloro­phen­yl)-2,2′-(m-phenyl­enedi­oxy)diquinazolin-4(3H)-one

Hai-Zhou Yang; Hai-Tao Gao; Xu-Hong Yang

doi:10.1107/S1600536808040567

. 2008 Dec 10;65(Pt 1):o59–o60. doi: 10.1107/S1600536808040567

3,3′-Bis(4-chlorophenyl)-2,2′-(m-phenylenedioxy)diquinazolin-4(3H)-one

Hai-Zhou Yang ^a, Hai-Tao Gao ^b, Xu-Hong Yang ^c,^*

PMCID: PMC2967973 PMID: 21581700

Abstract

In the title compound, C₃₄H₂₀Cl₂N₄O₄, the two quinazoline heterocyclic systems and the adjacent chlorobenzene rings are not coplanar, but oriented at dihedral angles of 66.66 (13) and 52.48 (12)°, respectively. The quinazoline ring systems are nearly planar, with dihedral angles between the planes of the two rings of 5.43 (16) and 3.40 (14)°, and are oriented at dihedral angles of 79.73 (13) and 83.52 (13)° with respect to the adjacent benzene ring between them. Intermolecular C—H⋯O hydrogen bonds contribute to the stability of the structure. In addition, weak π–π stacking interactions [centroid-to-centroid distances = 3.872 (1) and 3.876 (1) Å] are observed in the crystal structure.

Related literature

Many derivatives of quinazoline-4(3H)-one have been prepared, and their biological properties, such as antimicrobial, antidiabetic, anticonvulsant, antibacterial and antifungal activities, and their action as protein tyrosine kinase inhibitors, EGFR inhibitors and PDGFR phosphorylation inhibitors, have been studied by: Pandeya et al. (1999 ▶); Shiba et al. (1997 ▶); Malamas & Millen (1991 ▶); Mannschreck et al. (1984 ▶); Kung et al. (1999 ▶); Bartroli et al. (1998 ▶); Palmer et al. (1997 ▶); Tsou et al. (2001 ▶); Matsuno et al. (2002 ▶). For the synthesis, see: Yang et al. (2008 ▶). For related structures, see: Hu et al. (2006 ▶); Qu et al. (2008 ▶); Zeng et al. (2008 ▶); Sun et al. (2008 ▶).

Experimental

Crystal data

C₃₄H₂₀Cl₂N₄O₄
M _r = 619.44
Monoclinic,
a = 28.043 (2) Å
b = 11.3563 (8) Å
c = 21.5497 (16) Å
β = 122.7440 (10)°
V = 5772.2 (7) Å³
Z = 8
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 296 (2) K
0.23 × 0.10 × 0.10 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: none
22711 measured reflections
6251 independent reflections
3432 reflections with I > 2σ(I)
R _int = 0.069

Refinement

R[F ² > 2σ(F ²)] = 0.066
wR(F ²) = 0.160
S = 1.01
6251 reflections
397 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.28 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/S1600536808040567/at2685sup1.cif

e-65-00o59-sup1.cif^{(26.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808040567/at2685Isup2.hkl

e-65-00o59-Isup2.hkl^{(306.1KB, 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
C20—H20⋯O2ⁱ	0.93	2.34	3.234 (3)	162

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors are grateful to Xianning College for financial support of this work and providing laboratory and analytical facilities. The authors also acknowledge the Sophisticated Analytical Instrument Facility, Central China Normal University, Whuhan, for the data collection.

supplementary crystallographic information

Comment

Quinazoline 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 present here the synthesis and 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 of (I), the quinazoline heterocycle N1—C7/C8–C13/N2—C14 and N3—C22/C23–C28/N4—C21 and the adjacent chlorobenzene ring C1–C6 and C29–C34 are not co-planar, but oriented at the dihedral angles of 66.66 (13) and 52.48 (12)°, respectively. The nearly planar quinazoline ring system N1—C7/C8–C13/N2—C14 and N3—C22/C23–C28/N4—C21 are oriented with respect to the adjacent ring C15–C20 at the dihedral angles of 79.73 (13) and 83.52 (13)°, respectively.

Significant intramolecular C—H···O hydrogen bonds contribute to the stability of the molecular configuration (Fig. 2 and Table 1). The crystal structure (Fig. 2) is also stabilized by weak π–π (Table 1) stacking interactions with centroid–centroid separations of 3.872 (1) and 3.876 (1) Å for Cg2···Cg2ⁱ and Cg2···Cg6ⁱ, respectively, where Cg2 and Cg6 are the centroids of rings N3/C21—N4/C28—C27/C22 and C22–C27, respectively [symmetry code: (i) 1 - x, -y, 1 - z].

Experimental

To a solution of iminophosphorane (1.40 g, 3.0 mmol) in anhydrous THF (10 ml) was added 4-chlorophenyl isocyanate (3 mmol) under nitrogen at room temperature. After reaction, the mixture was allowed to stand for 10 h at 273–278 K, the solvent was removed under reduced pressure and diethyl ether/petroleum ether (1:2 v/v, 20 ml) was added to precipitate triphenylphosphine oxide. After filtration, the solvent was removed to give 1-(4-chlorophenyl)-3-(2-ethoxycarbonylphenyl) carbodiimide, which was used directly without further purification. To a solution of 1-(4-chlorophenyl)-3-(2-ethoxycarbonylphenyl) carbodiimide in THF (15 ml) was added m-dihydroxybenzene (0.18 g, 3 mmol). After the reaction mixture was allowed to stand for 0.5 h, the solvent was removed and anhydrous ethanol (10 ml) with several drops of EtONa in EtOH was added. The mixture was stirred for 2 h at room temperature. The solution was concentrated under reduced pressure and the residue was recrystallized from ethanol to give the title compound, (I). The product was recrystallized from methanol–dichloromethane (1:1 v/v, 20 ml) at room temperature to give crystals suitable for X-ray diffraction [m.p. 444 K, yield 45%].