2-[(Cyclo­hex-3-en-1-ylmeth­oxy)meth­yl]-6-phenyl-1,2,4-triazine-3,5(2H,4H)-dione

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

doi:10.1107/S1600536812021198

. 2012 May 19;68(Pt 6):o1776–o1777. doi: 10.1107/S1600536812021198

2-[(Cyclohex-3-en-1-ylmethoxy)methyl]-6-phenyl-1,2,4-triazine-3,5(2H,4H)-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: PMC3379356 PMID: 22719554

Abstract

In the title 1,2,4-triazine derivative, C₁₇H₁₉N₃O₃, the heterocyclic ring is planar (r.m.s. deviation = 0.040 Å) and effectively coplanar with the adjacent phenyl ring [dihedral angle = 4.5 (2)°] but almost perpendicular to the (cyclohex-3-en-1-ylmethoxy)methyl residue [N—N—C—O torsion angle = 71.6 (5)°], so that the molecule has an ‘L’ shape. Supramolecular chains along [001] are formed in the crystal via N—H⋯O hydrogen bonds where the acceptor O atom is the ether O atom. The adjacent carbonyl O atom forms a complementary C—H⋯O contact resulting in the formation of a seven-membered {⋯HNCO⋯HCO} heterosynthon; the second carbonyl O atom forms an intramolecular C—H⋯O contact. Chains are connected into a supramolecular layer in the ac plane by π–π interactions [ring centroid–centroid distance = 3.488 (3) Å]. The central atom in the –CH₂CH₂C(H)= residue of the cyclohexene ring is disordered over two sites, with the major component having a site-occupancy factor of 0.51 (2).

Related literature

For the potential medicinal applications of 1,2,4-triazines, see: Ban et al. (2010 ▶); Irannejad et al. (2010 ▶); Sangshetti & Shinde (2010 ▶). For the synthesis, see: El-Brollosy (2008 ▶). graphic file with name e-68-o1776-scheme1.jpg

Experimental

Crystal data

C₁₇H₁₉N₃O₃
M _r = 313.35
Monoclinic,
a = 4.7924 (6) Å
b = 13.7083 (19) Å
c = 11.8293 (15) Å
β = 101.538 (12)°
V = 761.43 (17) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.35 × 0.15 × 0.03 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.806, T _max = 1.000
4230 measured reflections
1757 independent reflections
1158 reflections with I > 2σ(I)
R _int = 0.078

Refinement

R[F ² > 2σ(F ²)] = 0.061
wR(F ²) = 0.133
S = 1.04
1757 reflections
212 parameters
4 restraints
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.30 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/S1600536812021198/su2425sup1.cif

e-68-o1776-sup1.cif^{(20.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812021198/su2425Isup2.hkl

e-68-o1776-Isup2.hkl^{(86.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812021198/su2425Isup3.cml

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
N1—H1⋯O3ⁱ	0.88	2.00	2.877 (5)	174
C2—H2⋯O1	0.95	2.21	2.880 (7)	127
C10—H10B⋯O2ⁱⁱ	0.99	2.46	3.352 (6)	150

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

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. The authors 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

Several 1,2,4-triazines have been shown to exhibit herbicidal, anti-viral, anti-microbial, anti-inflammatory, anti-malarial, anti-cancer, anti-proliferative and neuroprotective activities (Ban et al., 2010; Irannejad et al., 2010; Sangshetti & Shinde, 2010). The title compound (I), was originally synthesized as a potential anti-microbial agent (El-Brollosy, 2008). Herein, we describe the results of its crystal structure determination.

The six ring atoms comprising the 2,4-dihydro-1,2,4-triazine-3,5-dione residue in (I), Fig. 1, are co-planar with a r.m.s. = 0.040 Å; the maximum deviations from their least-squares plane being 0.035 (5) Å for the C7 atom and -0.039 (5) Å for the C8 atom. The dihedral angle between this ring and the attached phenyl ring of 4.5 (2)° is consistent with an almost co-planar relationship. The (cyclohex-3-en-1-ylmethoxy)methyl residue lies perpendicular to the rest of the molecule as seen in the value of the N3—N2—C10—O3 torsion angle of 71.6 (5)°, so that to a first approximation the molecule has an L-shape.

The crystal structure features supramolecular chains along [001]. These are mediated by, perhaps surprisingly, N—H···O hydrogen bonds where the O atom is the ether O atom, rather than carbonyl O atoms. The adjacent carbonyl-O2 atom forms a complementary C—H···O contact resulting in the formation of a seven-membered {···HNCO···HCO} heterosynthon, Fig. 2 and Table 1. The carbonyl-O1 atom forms an intramolecular C—H..O interaction. The chains are connected into supramolecular layers in the ac plane by π—π interactions [ring centroid(N1–N3,C7–C9)···centroid(C1–C6)ⁱ = 3.488 (3) Å and tilt angle = 4.5 (2)°; symmetry code: (i) x+1, y, z], Fig. 3. Supramolecular layers stack along the b axis with no specific interactions between them, Fig. 4.

Experimental

5-Phenyl-6-azauracil (0.189 g, 1 mmol) was stirred in dry acetonitrile (15 ml) under nitrogen and N,O-bis-trimethylsilylacetamide (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 trifluoromethanesulphonate (0.18 ml, 1 mmol) was added followed by the drop wise addition of bis(3-cyclohexen-1-ylmethoxy)methane (0.472 g, 2 mmol). The reaction mixture was stirred at room temperature for 5 h. The reaction was quenched by addition of sat. aq. NaHCO₃ solution (5 ml). The mixture was evaporated under reduced pressure and the residue was extracted with ether (3 x 50 ml). The combined ether fractions were collected, dried (MgSO₄) and evaporated under reduced pressure. The residue was purified on a silica gel column using 1:5 petroleum ether / chloroform to give the title compound in 64% (0.199 g) yield. Colourless crystals were obtained upon crystallization from its ethanol solution (El-Brollosy, 2008).