6-Methyl-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/S1600536812020429

. 2012 May 19;68(Pt 6):o1768–o1769. doi: 10.1107/S1600536812020429

6-Methyl-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: PMC3379351 PMID: 22719549

Abstract

In the title compound, C₂₀H₂₀N₂O₃, the ten atoms comprising the quinazoline ring are essentially planar (r.m.s. deviation = 0.024 Å), and this plane is almost orthogonal to the terminal phenyl ring [dihedral angle = 82.87 (7)°]. The conformation about the ethylene bond [1.335 (2) Å] is E and there is a significant twist between this residue and the adjacent phenyl ring [C—C—C— torsion angle = −48.4 (3)°]. The crystal structure features centrosymmetric dimeric units linked by pairs of N—H⋯O hydrogen bonds between the amide groups which lead 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 [centroid–centroid distances = 3.5087 (8) and 3.5645 (9) 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-o1768-scheme1.jpg

Experimental

Crystal data

C₂₀H₂₀N₂O₃
M _r = 336.38
Monoclinic,
a = 16.2352 (8) Å
b = 13.6934 (6) Å
c = 7.8900 (4) Å
β = 102.606 (5)°
V = 1711.78 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.40 × 0.20 × 0.10 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.522, T _max = 1.000
13993 measured reflections
3965 independent reflections
3067 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.129
S = 1.02
3965 reflections
232 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.25 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/S1600536812020429/hg5224sup1.cif

e-68-o1768-sup1.cif^{(20.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020429/hg5224Isup2.hkl

e-68-o1768-Isup2.hkl^{(194.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812020429/hg5224Isup3.cml

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

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

Cg2 and Cg3 are the centroids of the C8–C8 and C15–C20 benzene rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1n⋯O2ⁱ	0.93 (2)	1.89 (2)	2.8180 (16)	172.9 (17)
C10—H10B⋯O1ⁱⁱ	0.99	2.49	3.3001 (18)	139
C11—H11B⋯O3ⁱⁱⁱ	0.99	2.56	3.4462 (18)	150
C14—H14⋯Cg3^iv	0.95	2.85	3.5574 (18)	132
C18—H18⋯Cg2^iv	0.95	2.91	3.680 (2)	139

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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

In continuation of our interest in chemistry of non-nucleoside reverse transcriptase inhibitors (NNRTI's) (El-Brollosy et al., 2008; El-Brollosy et al., 2009), relevant to the treatment of human immunodeficiency virus (HIV) (Hopkins et al., 1996; Hopkins et al., 1999), we synthesized the title compound, 6-methyl-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 to complement the structure determination of the recently determined chloro analogue (El-Brollosy et al., 2012).

The 10 atoms comprising the quinazoline ring in (I), Fig. 1, are co-planar with a r.m.s. = 0.024 Å; the maximum deviations from their least-squares plane are 0.036 (1) Å for the C2 atom and -0.032 (1) Å for the N2 atom. The dihedral angle between the fused ring system and the terminal phenyl ring of 82.87 (7)° is consistent with an almost orthogonal relationship. The conformation about the ethylene bond [C12═C14 = 1.335 (2) Å] is E. The torsion angle between the ethylene and phenyl rings, i.e. C12—C14—C15—C16, of -48.4 (3)° indicates a significant twist about the C14—C15 bond. Overall, the molecule in (I) is significantly more twisted than that observed in the chloro analogue (El-Brollosy et al., 2012).

In the crystal structure, 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) which lead to eight-membered {···HNCO}₂ synthons, Table 1. The dimeric aggregates are consolidated into a three-dimensional architecture by C—H···O and C—H···π interactions, Table 1, as well as by π—π contacts [ring centroid(N1,N2,C1–C3,C8)···centroid(N1,N2,C1–C3,C8)ⁱ = 3.5087 (8) Å and tilt angle = 0° and ring centroid(N1,N2,C1–C3,C8)···centroid(C3–C8)ⁱ = 3.5645 (9) Å and tilt angle = 1.85 (7)°, for symmetry operation i: 1 - x, 1 - y, -z). Globally, the crystal structure comprises alternating layers of quinazoline rings and 2-methyl-3-phenylallyloxy)methyl residues that stack along the a axis, Fig. 2.

Experimental

6-Methylquinazoline-2,4(1H,3H)dione (0.176 g, 1 mmol) was stirred in dry acetonitrile (15 ml) under nitrogen and N,O-bis(trimethylsilyl)acetamide (0.87 ml, 3.5 mmol) was 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, after which the reaction was quenched by the addition of sat. 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 on silica gel column chromatography, using 20% ether in petroleum ether (40–60°C), to afford the title compound as a white solid in 78% yield (0.262 g). Single crystals were achieved by recrystallization from its ethanol solution (El-Brollosy 2007).