2-Benzyl­sulfanyl-4-[(4-methyl­phen­yl)sulfan­yl]-6-pentyl­pyrimidine-5-carbonitrile

Ali A El-Emam; Omar A Al-Deeb; Nasser R El-Brollosy; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812025275

. 2012 Jun 13;68(Pt 7):o2054. doi: 10.1107/S1600536812025275

2-Benzylsulfanyl-4-[(4-methylphenyl)sulfanyl]-6-pentylpyrimidine-5-carbonitrile

Ali A El-Emam ^a,^‡, Omar A Al-Deeb ^a, Nasser R El-Brollosy ^a, Seik Weng Ng ^b,^c, Edward R T Tiekink ^b,^*

PMCID: PMC3393321 PMID: 22807878

Abstract

In the title compound, C₂₄H₂₅N₃S₂, the S-bound benzene rings have orthogonal [dihedral angle = 85.31 (9)°] and splayed [67.92 (11)°] orientations with respect to the pyrimidine ring; the dihedral angle between the benzene rings is 48.18 (12)°. The pentyl group has an extended all-trans conformation and lies to one side of the pyrimidine ring [the N_py—C_py—C_p—C_p torsion angle = −85.7 (2)°; py = pyrimidine and p = pentyl].

Related literature

For the chemotherapeutic activity of pyrimidine derivatives see: Ghoshal & Jacob (1997 ▶); De Corte (2005 ▶); Al-Omar et al. (2010 ▶); Al-Abdullah et al. (2011 ▶); Al-Turkistani et al. (2011 ▶). For a related pyrimidine structure, see: El-Emam et al. (2012 ▶).

Experimental

Crystal data

C₂₄H₂₅N₃S₂
M _r = 419.59
Monoclinic,
a = 9.9178 (2) Å
b = 8.2235 (2) Å
c = 28.4388 (8) Å
β = 96.115 (2)°
V = 2306.24 (10) Å³
Z = 4
Cu Kα radiation
μ = 2.19 mm⁻¹
T = 294 K
0.40 × 0.20 × 0.10 mm

Data collection

Agilent SuperNova Dual diffractometer with Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.689, T _max = 1.000
9523 measured reflections
4746 independent reflections
3720 reflections with I > 2σ(I)
R _int = 0.017

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.138
S = 1.03
4746 reflections
264 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); 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 for Windows (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/S1600536812025275/zl2483sup1.cif

e-68-o2054-sup1.cif^{(21.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812025275/zl2483Isup2.hkl

e-68-o2054-Isup2.hkl^{(232.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812025275/zl2483Isup3.cml

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

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

The ability of of pyrimidine derivatives to inhibit vital enzymes responsible for DNA bio-synthesis is the reason behind their chemotherapeutic efficacy. Thus, several pyrimidine non-nucleoside derivatives exhibit anti-cancer (Ghoshal & Jacob, 1997), anti-viral (De Corte, 2005) and anti-bacterial activities (Al-Abdullah et al., 2011). The synthesis and crystal structure determination of the title compound, was undertaken in connection with on-going studies of the chemical, pharmacological and structural properties of pyrimidine derivatives (Al-Omar et al., 2010; Al-Turkistani et al., 2011; El-Emam et al. 2012).

With reference to the pyrimidine ring (r.m.s. deviation = 0.011 Å) in the title compound, Fig. 1, the S1- and S2-bound benzene rings form dihedral angles of 85.31 (9) and 67.92 (11)°, respectively, which indicate an orthogonal and a splayed orientation, respectively; the dihedral angle between the benzene rings is 48.18 (12)°. The pentyl group lies to one side of the pyrimidine ring with the N2—C3—C20—C21 torsion angle being -85.7 (2)°. The remaining chain has an extended all-trans conformation [the C20—C21—C22—C23 and C21—C22—C23—C24 torsion angles are -173.8 (2) and 179.6 (2)°, respectively].

No specific intermolecular interactions are evident in the crystal structure. Globally, molecules lie in layers in the ab plane which stack along the c axis, Fig. 2.

Experimental

To a solution of 2-(benzylsulfanyl)-4-chloro-6-(n-pentyl)pyrimidine-5-carbonitrile (665 mg, 2 mmol) in dry pyridine (3 ml), 4-thiocresol (248 mg, 2 mmol) was added and the mixture was heated under reflux for 6 h. On cooling, the solvent was then distilled off in vacuo and water (5 ml) was added to the residue. The separated precipitate was collected by filtration, washed with cold water, dried and recrystallized from ethanol to yield 747 mg (89%) of the title compound as colourless crystals. M.p.: 384–386 K. Single crystals suitable for X-ray analysis were obtained by slow evaporation of a solution of the title compound in CHCl₃:EtOH (1:1, 5 ml) at room temperature. ¹H NMR (DMSO-d₆, 500.13 MHz): δ 0.85 (t, 3H, CH₃, J = 7.0 Hz), 1.26–1.34 (m, 4H, CH₂CH₂CH₃), 1.64–1.69 (m, 2H, CH₂CH₂CH₂CH₃), 2.27 (s, 3H, Ar—CH₃), 2.76 (t, 2H, CH₂CH₂CH₂CH₂CH₃, J = 7.0 Hz), 4.02 (s, 2H, CH₂S), 6.98–6.99 (m, 2H, Ar—H), 7.21–7.23 (m, 3H, Ar—H), 7.28 (d, 2H, Ar—H, J = 8.0 Hz), 7.51 (d, 2H, Ar—H, J = 8.0 Hz). ¹³C NMR (DMSO-d₆, 125.76 MHz): δ 14.16 (CH₃), 21.29 (CH₂CH₃), 22.29 (ArCH₃), 27.39 (CH₂CH₂CH₃), 31.13 (CH₂CH₂CH₂CH₃), 34.51 (CH₂CH₂CH₂CH₂CH₃), 36.12 (CH₂S), 99.14 (C-5), 114.69 (CN), 122.19, 127.56, 128.74, 129.01, 130.67, 136.20, 137.58, 140.99 (Ar—C), 172.81, 173.15, 173.37 (C-2, C-4 & C-6).