6-Chloro-1-({[(2E)-2-methyl-3-phenyl­prop-2-en-1-yl]­oxy}meth­yl)-1,2,3,4-tetra­hydro­quinazoline-2,4-dione

Nasser R El-Brollosy; Mohamed I Attia; Ali A El-Emam; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812020405

. 2012 May 19;68(Pt 6):o1770–o1771. doi: 10.1107/S1600536812020405

6-Chloro-1-({[(2E)-2-methyl-3-phenylprop-2-en-1-yl]oxy}methyl)-1,2,3,4-tetrahydroquinazoline-2,4-dione

Nasser R El-Brollosy ^a,^b,^‡, Mohamed I Attia ^a, Ali A El-Emam ^a, Seik Weng Ng ^c,^d, Edward R T Tiekink ^c,^*

PMCID: PMC3379352 PMID: 22719550

Abstract

In the title compound, C₁₉H₁₇ClN₂O₃, the conformation about the ethylene bond [1.333 (2) Å] is E. The ten atoms comprising the quinazoline ring are essentially planar (r.m.s. deviation = 0.032 Å) and their mean plane forms a dihedral angle of 13.89 (7)° with the terminal phenyl ring; the molecule has an open conformation as these substituents are directed away from each other. In the crystal, centrosymmetrically related molecules are connected via N—H⋯O hydrogen bonds between the amide groups, leading to eight-membered {⋯HNCO}₂ synthons. These are consolidated into a three-dimensional architecture by C—H⋯O, C—H⋯π and π–π interactions [ring centroid(N₂C₄)⋯centroid(C₆) distance = 3.5820 (11) Å].

Related literature

For background to non-nucleoside reverse transcriptase inhibitors, see: Hopkins et al. (1996 ▶, 1999 ▶); El-Brollosy et al. (2008 ▶, 2009 ▶). For a related structure, see: El-Brollosy et al. (2012 ▶). For the synthesis, see: El-Brollosy (2007 ▶). graphic file with name e-68-o1770-scheme1.jpg

Experimental

Crystal data

C₁₉H₁₇ClN₂O₃
M _r = 356.80
Triclinic,
a = 7.6179 (3) Å
b = 9.8168 (4) Å
c = 11.7009 (6) Å
α = 73.937 (4)°
β = 83.651 (3)°
γ = 80.942 (3)°
V = 828.31 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 100 K
0.35 × 0.30 × 0.15 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.904, T _max = 1.000
13263 measured reflections
3817 independent reflections
3107 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.114
S = 1.04
3817 reflections
231 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812020405/hg5225sup1.cif

e-68-o1770-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020405/hg5225Isup2.hkl

e-68-o1770-Isup2.hkl^{(187.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812020405/hg5225Isup3.cml

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

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

Cg1 is the centroid of the C14–C19 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1n⋯O2ⁱ	0.85 (2)	2.05 (2)	2.8932 (18)	168.9 (19)
C4—H4⋯O1ⁱⁱ	0.95	2.57	3.382 (2)	144
C5—H5⋯O3ⁱⁱⁱ	0.95	2.57	3.427 (2)	150
C9—H9B⋯O1ⁱⁱ	0.99	2.38	3.232 (2)	144
C10—H10A⋯Cg1^iv	0.99	2.69	3.612 (2)	154

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

The financial support of the Deanship of Scientific Research and the Research Center of the College of Pharmacy, King Saud University is greatly appreciated. We also thank the Ministry of Higher Education (Malaysia) for funding structural studies through the High-Impact Research scheme (UM.C/HIR/MOHE/SC/12).

supplementary crystallographic information

Comment

Non-nucleoside reverse transcriptase inhibitors (NNRTI's) are very promising therapies in the treatment of human immunodeficiency virus (HIV) (Hopkins et al., 1996; Hopkins et al., 1999). In continuation to our interest in the chemistry of NNRTI's (El-Brollosy et al., 2008; El-Brollosy et al., 2009), we synthesized the title compound, 6-chloro-1-[((E)-2-methyl-3-phenylallyloxy)methyl]quinazoline-2,4(1H,3H)-dione (I), as a potential NNRTI (El-Brollosy, 2007). Herein, we describe the results of its crystal structure determination and relate this to the structure of the recently determined methyl analogue (El-Brollosy et al., 2012).

In (I), Fig. 1, the conformation about the ethylene bond [C11═C13 = 1.333 (2) Å] is E. The 10 atoms comprising the quinazoline ring are planar with a r.m.s. = 0.032 Å; the maximum deviations from the least-squares plane = 0.051 (2) Å for the C1 atom and -0.046 (2) Å for the C2 atom. The dihedral angle between the fused ring system and the terminal phenyl ring of 13.89 (7)° is consistent with a twisted molecule; these substituents are directed away from each other so that the molecule has an open conformation. The torsion angle between the ethylene and phenyl rings, i.e. C11—C13—C14—C15, of 25.9 (3)° indicates a significant twist in this region of the molecule. However twisted the molecule of (I) is, it is less twisted than the methyl analogue where the dihedral angle between the quinazoline and phenyl rings was found to be 82.87 (7)° (El-Brollosy et al., 2012).

Centrosymmetrically related molecules are connected via N—H···O hydrogen bonds between the amide groups (involving the carbonyl-O closest to the tertiary-N atom) and lead to eight-membered {···HNCO}₂ synthons, Table 1. These are consolidated into a three-dimensional architecture by C—H···O and C—H···π interactions, Table 1, and π—π contacts [ring centroid(N1,N2,C1–C3,C8)···centroid(C14–C19)ⁱ = 3.5820 (11) Å and tilt angle = 13.17 (9)°, for symmetry operation i: -x, 1 - y, 1 - z). Globally, the crystal structure comprises alternating layers of quinazoline rings and 2-methyl-3-phenylallyloxy)methyl residues that stack along the b axis, Fig. 2.

Experimental

6-Chloroquinazoline-2,4(1H,3H)-dione (0.197 g, 1 mmol) was stirred in dry acetonitrile (15 ml) under nitrogen and N,O-bis(trimethylsilyl)acetamide (0.87 ml, 3.5 mmol) added. After a clear solution was obtained (10 min), the mixture was cooled to 223 K, and trimethylsilyl trifluoromethanesulfonate (0.18 ml, 1 mmol) was added followed by the drop wise addition of bis[(E)-2-methyl-3-phenylallyloxy]methane (0.616 g, 2 mmol). The reaction mixture was stirred at room temperature for 5 h. The reaction was quenched by the addition of saturated aq. NaHCO₃ solution (5 ml). The mixture was evaporated under reduced pressure and the residue was extracted with ether (3 × 50 ml). The combined ether fractions were collected, dried (MgSO₄) and evaporated under reduced pressure. The product was purified by silica gel column chromatography, using 20% ether in petroleum ether (40–60 °C), to afford the title compound as a white solid in 81% yield (0.288 g). Single crystals were achieved by crystallization from its ethanol solution (El-Brollosy, 2007).