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Acta Cryst. (2008). E64, o1768    [ doi:10.1107/S1600536808025592 ]

6-Cyclohexylmethyl-2-cyclohexylsulfanyl-5-isopropylpyrimidin-4(3H)-one

C.-S. Zhang, D.-X. Li, D.-H. Zhang, Y.-P. He and C. Li

Abstract top

The title compound, C20H32N2OS, was obtained during the course of our investigation on 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin-4(3H)-ones (S-DABOs) showing favourable anti-HIV-1 activity. Both cyclohexane rings adopt chair conformations. The angle at the methylene C atom linking the pyrimidine and cyclohexane ring is 113.7 (3)°, which is in the range considered optimal for maximum activity of non-nucleoside reverse transcriptase inhibitors. Intermolecular N-H...O hydrogen bonds link the molecules into dimers and stabilize the crystal structure of the compound. In addition, an intramolecular C-H...O hydrogen bond is observed.

Comment top

As part of our ongoing investigation of S-DABO analogues which are a potent family of non-nucleoside reverse transcriptase inhibitors (NNRTIs), the title compound was synthesized as a novel inhibitor and shows favourable anti-HIV-1 activity.

The molecular structure is shown in Fig. 1. Both cyclohexane rings adopt the lowest energy chair conformation. C13—C14—C5 is 113.7 (3)°, which is in the range considered optimal for maximum activity of NNRTIs, viz. 110°–115° (Ettorre et al., 1996).

A comparision of the crystal structure of the title compound with some reported S-DABOs show that their spatial arrangement is similar (Ettorre et al., 1998; Rao et al., 2007). Although these molecules assume a similar conformation, they show differences in their activities. Thus, futher structural investigations are needed.

Intermolecular N—H···O hydrogen bonds link the molecules into dimers and stabilize the crystal structure of the compound. In addition, an intramolecular C—H···O hydrogen bond is observed.

Related literature top

For related literature, see: He et al. (2004); Ettorre et al. (1996, 1998); Rao et al. (2007).

Experimental top

With 2-cyclohexylacetonitrile as the starting material, the title compound was synthesized according to the procedure of He et al. (2004). Single crystals were obtained from a mixture of ethyl acetate and petroleum ether by slow evaporation at room temperature.

Refinement top

Methyl H atoms were placed in calculated positions with C—H = 0.96 Å and the torsion angle was refined to fit the electron density; Uiso(H) = 1.5Ueq(C). Other H atoms were placed in calculated positions with C—H = 0.97–0.98 Å and N—H = 0.86 Å, and refined in riding mode; Uiso(H) = 1.2Ueq(C, N).

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom labelling scheme and 30% probability displacement ellipsoids.
[Figure 2] Fig. 2. The crystal packing of title compound showing the intermolecular hydrogen bonding (dashed lines)
6-Cyclohexylmethyl-2-cyclohexylsulfanyl-5-isopropylpyrimidin-4(3H)-one top
Crystal data top
C20H32N2OSZ = 2
Mr = 348.54F000 = 380
Triclinic, P1Dx = 1.122 Mg m−3
a = 9.9549 (16) ÅMo Kα radiation
λ = 0.71073 Å
b = 10.9542 (17) ÅCell parameters from 4697 reflections
c = 12.1054 (19) Åθ = 1.9–28.3º
α = 63.250 (2)ºµ = 0.17 mm−1
β = 69.195 (2)ºT = 298 (2) K
γ = 63.033 (2)ºBlock, colourless
V = 1031.5 (3) Å30.19 × 0.14 × 0.12 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer		4697 independent reflections
Radiation source: fine-focus sealed tube2103 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.047
T = 298(2) Kθmax = 28.3º
φ and ω scansθmin = 1.9º
Absorption correction: multi-scan
(SADABS; Bruker, 1998)		h = −13→13
Tmin = 0.969, Tmax = 0.980k = −13→14
9017 measured reflectionsl = −16→15
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.065H-atom parameters constrained
wR(F2) = 0.216  w = 1/[σ2(Fo2) + (0.1P)2 + 0.3399P]
where P = (Fo2 + 2Fc2)/3
S = 0.88(Δ/σ)max < 0.001
4697 reflectionsΔρmax = 0.18 e Å−3
219 parametersΔρmin = −0.20 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C20H32N2OSγ = 63.033 (2)º
Mr = 348.54V = 1031.5 (3) Å3
Triclinic, P1Z = 2
a = 9.9549 (16) ÅMo Kα
b = 10.9542 (17) ŵ = 0.17 mm−1
c = 12.1054 (19) ÅT = 298 (2) K
α = 63.250 (2)º0.19 × 0.14 × 0.12 mm
β = 69.195 (2)º
Data collection top
Bruker SMART CCD area-detector
diffractometer		4697 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1998)		2103 reflections with I > 2σ(I)
Tmin = 0.969, Tmax = 0.980Rint = 0.047
9017 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.065219 parameters
wR(F2) = 0.216H-atom parameters constrained
S = 0.88Δρmax = 0.18 e Å−3
4697 reflectionsΔρmin = −0.20 e Å−3
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)are estimated using the full covariance matrix. The cell e.s.d.'s are takeninto account individually in the estimation of e.s.d.'s in distances, anglesand torsion angles; correlations between e.s.d.'s in cell parameters are onlyused when they are defined by crystal symmetry. An approximate (isotropic)treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc, and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.33860 (11)0.15552 (12)0.30395 (9)0.0638 (3)
O1−0.1114 (3)0.0731 (3)0.6134 (2)0.0669 (8)
N10.1985 (3)0.2729 (3)0.4863 (2)0.0473 (7)
N20.0978 (3)0.1230 (3)0.4780 (2)0.0514 (7)
H20.10690.06830.44050.062*
C8−0.0217 (4)0.1378 (4)0.5792 (3)0.0492 (8)
C70.2013 (4)0.1900 (4)0.4349 (3)0.0465 (8)
C130.0816 (3)0.2939 (3)0.5876 (3)0.0439 (8)
C9−0.0283 (4)0.2320 (4)0.6356 (3)0.0492 (8)
C10−0.1620 (4)0.2617 (4)0.7421 (4)0.0686 (11)
H10−0.14770.32550.77020.082*
C140.0877 (4)0.3902 (4)0.6429 (3)0.0522 (9)
H14A−0.01490.45920.65850.063*
H14B0.15210.44560.58170.063*
C60.4652 (4)0.2481 (4)0.2780 (3)0.0551 (9)
H60.40210.34530.28330.066*
C150.1495 (4)0.3055 (4)0.7659 (3)0.0531 (9)
H150.09980.23290.81880.064*
C50.5566 (5)0.2656 (5)0.1449 (4)0.0801 (13)
H5A0.48710.32520.08570.096*
H5B0.61060.17060.13560.096*
C10.5698 (4)0.1675 (4)0.3730 (4)0.0675 (11)
H1A0.62760.06840.37340.081*
H1B0.50870.16280.45660.081*
C200.3203 (4)0.2241 (4)0.7442 (4)0.0671 (11)
H20A0.37200.29300.68760.081*
H20B0.34310.15590.70390.081*
C160.1092 (5)0.4041 (5)0.8375 (4)0.0779 (12)
H16A0.15370.47950.78570.094*
H16B−0.00140.45140.85450.094*
C180.3361 (5)0.2395 (5)0.9399 (4)0.0860 (13)
H18A0.36730.18051.02100.103*
H18B0.38980.30840.89470.103*
C20.6803 (5)0.2449 (5)0.3405 (4)0.0806 (13)
H2A0.62250.34180.34550.097*
H2B0.74770.19100.40130.097*
C40.6718 (6)0.3368 (6)0.1148 (4)0.1012 (17)
H4A0.73430.33890.03200.121*
H4B0.61680.43690.11240.121*
C170.1662 (5)0.3218 (6)0.9600 (4)0.0909 (15)
H17A0.14300.39001.00030.109*
H17B0.11310.25381.01580.109*
C190.3812 (5)0.1413 (5)0.8657 (4)0.0842 (13)
H19A0.49220.09850.84660.101*
H19B0.34150.06240.91700.101*
C30.7749 (5)0.2569 (6)0.2104 (6)0.1060 (18)
H3A0.83830.16000.20680.127*
H3B0.84200.30900.19080.127*
C12−0.1652 (6)0.1229 (6)0.8561 (4)0.0948 (15)
H12A−0.18530.06000.83350.142*
H12B−0.24460.14830.92390.142*
H12C−0.06790.07320.88230.142*
C11−0.3132 (4)0.3452 (5)0.6950 (5)0.0978 (16)
H11A−0.30700.43200.62450.147*
H11B−0.39490.37140.76130.147*
H11C−0.33300.28460.66940.147*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0637 (6)0.0911 (8)0.0556 (6)−0.0395 (6)0.0099 (4)−0.0446 (6)
O10.0614 (16)0.088 (2)0.0772 (18)−0.0426 (15)0.0112 (13)−0.0516 (16)
N10.0487 (16)0.0526 (17)0.0457 (16)−0.0201 (14)−0.0045 (12)−0.0222 (14)
N20.0519 (16)0.0645 (19)0.0499 (16)−0.0248 (15)0.0003 (13)−0.0329 (15)
C80.0451 (19)0.059 (2)0.051 (2)−0.0177 (17)−0.0052 (15)−0.0282 (17)
C70.0478 (19)0.052 (2)0.0429 (18)−0.0194 (16)−0.0072 (14)−0.0181 (16)
C130.0449 (18)0.046 (2)0.0426 (18)−0.0123 (15)−0.0075 (14)−0.0211 (16)
C90.0432 (18)0.058 (2)0.053 (2)−0.0192 (16)−0.0007 (15)−0.0295 (17)
C100.063 (2)0.082 (3)0.080 (3)−0.037 (2)0.018 (2)−0.055 (2)
C140.052 (2)0.053 (2)0.057 (2)−0.0199 (17)−0.0023 (16)−0.0273 (18)
C60.061 (2)0.054 (2)0.052 (2)−0.0245 (18)0.0040 (17)−0.0273 (18)
C150.060 (2)0.062 (2)0.050 (2)−0.0301 (18)0.0006 (16)−0.0299 (18)
C50.099 (3)0.096 (3)0.058 (2)−0.060 (3)0.017 (2)−0.036 (2)
C10.058 (2)0.069 (3)0.072 (3)−0.022 (2)−0.015 (2)−0.020 (2)
C200.064 (2)0.076 (3)0.066 (2)−0.013 (2)−0.0122 (19)−0.040 (2)
C160.082 (3)0.091 (3)0.080 (3)−0.021 (2)−0.011 (2)−0.060 (3)
C180.093 (3)0.109 (4)0.074 (3)−0.038 (3)−0.018 (2)−0.043 (3)
C20.062 (3)0.075 (3)0.113 (4)−0.023 (2)−0.024 (3)−0.035 (3)
C40.130 (4)0.115 (4)0.079 (3)−0.089 (4)0.035 (3)−0.045 (3)
C170.091 (3)0.128 (4)0.080 (3)−0.033 (3)−0.005 (2)−0.072 (3)
C190.080 (3)0.094 (3)0.082 (3)−0.012 (2)−0.026 (2)−0.043 (3)
C30.067 (3)0.101 (4)0.168 (6)−0.042 (3)0.016 (3)−0.078 (4)
C120.112 (4)0.116 (4)0.066 (3)−0.066 (3)0.029 (3)−0.048 (3)
C110.053 (3)0.095 (4)0.133 (4)−0.021 (2)0.017 (3)−0.062 (3)
Geometric parameters (Å, °) top
S1—C71.748 (3)C1—H1B0.9700
S1—C61.817 (3)C20—C191.513 (5)
O1—C81.233 (4)C20—H20A0.9700
N1—C71.299 (4)C20—H20B0.9700
N1—C131.381 (4)C16—C171.505 (6)
N2—C71.353 (4)C16—H16A0.9700
N2—C81.383 (4)C16—H16B0.9700
N2—H20.8600C18—C171.502 (6)
C8—C91.441 (4)C18—C191.520 (6)
C13—C91.364 (4)C18—H18A0.9700
C13—C141.512 (4)C18—H18B0.9700
C9—C101.518 (4)C2—C31.503 (6)
C10—C111.523 (6)C2—H2A0.9700
C10—C121.531 (6)C2—H2B0.9700
C10—H100.9800C4—C31.509 (7)
C14—C151.531 (5)C4—H4A0.9700
C14—H14A0.9700C4—H4B0.9700
C14—H14B0.9700C17—H17A0.9700
C6—C11.514 (5)C17—H17B0.9700
C6—C51.516 (5)C19—H19A0.9700
C6—H60.9800C19—H19B0.9700
C15—C201.508 (5)C3—H3A0.9700
C15—C161.511 (5)C3—H3B0.9700
C15—H150.9800C12—H12A0.9600
C5—C41.521 (6)C12—H12B0.9600
C5—H5A0.9700C12—H12C0.9600
C5—H5B0.9700C11—H11A0.9600
C1—C21.523 (5)C11—H11B0.9600
C1—H1A0.9700C11—H11C0.9600
C7—S1—C6103.08 (16)C19—C20—H20B109.2
C7—N1—C13117.1 (3)H20A—C20—H20B107.9
C7—N2—C8123.4 (3)C17—C16—C15112.2 (4)
C7—N2—H2118.3C17—C16—H16A109.2
C8—N2—H2118.3C15—C16—H16A109.2
O1—C8—N2119.8 (3)C17—C16—H16B109.2
O1—C8—C9125.8 (3)C15—C16—H16B109.2
N2—C8—C9114.4 (3)H16A—C16—H16B107.9
N1—C7—N2122.9 (3)C17—C18—C19111.7 (4)
N1—C7—S1123.0 (3)C17—C18—H18A109.3
N2—C7—S1114.1 (2)C19—C18—H18A109.3
C9—C13—N1123.6 (3)C17—C18—H18B109.3
C9—C13—C14122.5 (3)C19—C18—H18B109.3
N1—C13—C14113.8 (3)H18A—C18—H18B107.9
C13—C9—C8118.6 (3)C3—C2—C1111.1 (4)
C13—C9—C10123.7 (3)C3—C2—H2A109.4
C8—C9—C10117.7 (3)C1—C2—H2A109.4
C9—C10—C11110.7 (3)C3—C2—H2B109.4
C9—C10—C12112.6 (3)C1—C2—H2B109.4
C11—C10—C12112.1 (3)H2A—C2—H2B108.0
C9—C10—H10107.0C3—C4—C5112.2 (4)
C11—C10—H10107.0C3—C4—H4A109.2
C12—C10—H10107.0C5—C4—H4A109.2
C13—C14—C15113.7 (3)C3—C4—H4B109.2
C13—C14—H14A108.8C5—C4—H4B109.2
C15—C14—H14A108.8H4A—C4—H4B107.9
C13—C14—H14B108.8C18—C17—C16111.4 (3)
C15—C14—H14B108.8C18—C17—H17A109.3
H14A—C14—H14B107.7C16—C17—H17A109.3
C1—C6—C5111.3 (3)C18—C17—H17B109.3
C1—C6—S1113.1 (3)C16—C17—H17B109.3
C5—C6—S1106.7 (2)H17A—C17—H17B108.0
C1—C6—H6108.5C20—C19—C18111.9 (4)
C5—C6—H6108.5C20—C19—H19A109.2
S1—C6—H6108.5C18—C19—H19A109.2
C20—C15—C16110.4 (3)C20—C19—H19B109.2
C20—C15—C14112.2 (3)C18—C19—H19B109.2
C16—C15—C14111.6 (3)H19A—C19—H19B107.9
C20—C15—H15107.5C2—C3—C4110.2 (4)
C16—C15—H15107.5C2—C3—H3A109.6
C14—C15—H15107.5C4—C3—H3A109.6
C6—C5—C4111.2 (3)C2—C3—H3B109.6
C6—C5—H5A109.4C4—C3—H3B109.6
C4—C5—H5A109.4H3A—C3—H3B108.1
C6—C5—H5B109.4C10—C12—H12A109.5
C4—C5—H5B109.4C10—C12—H12B109.5
H5A—C5—H5B108.0H12A—C12—H12B109.5
C6—C1—C2110.4 (3)C10—C12—H12C109.5
C6—C1—H1A109.6H12A—C12—H12C109.5
C2—C1—H1A109.6H12B—C12—H12C109.5
C6—C1—H1B109.6C10—C11—H11A109.5
C2—C1—H1B109.6C10—C11—H11B109.5
H1A—C1—H1B108.1H11A—C11—H11B109.5
C15—C20—C19112.1 (3)C10—C11—H11C109.5
C15—C20—H20A109.2H11A—C11—H11C109.5
C19—C20—H20A109.2H11B—C11—H11C109.5
C15—C20—H20B109.2
C7—N2—C8—O1−179.8 (3)C9—C13—C14—C1575.8 (4)
C7—N2—C8—C90.3 (5)N1—C13—C14—C15−103.1 (3)
C13—N1—C7—N2−1.4 (5)C7—S1—C6—C174.8 (3)
C13—N1—C7—S1178.5 (2)C7—S1—C6—C5−162.5 (3)
C8—N2—C7—N11.0 (5)C13—C14—C15—C2073.0 (4)
C8—N2—C7—S1−178.9 (2)C13—C14—C15—C16−162.6 (3)
C6—S1—C7—N14.1 (3)C1—C6—C5—C4−53.9 (5)
C6—S1—C7—N2−176.0 (2)S1—C6—C5—C4−177.7 (3)
C7—N1—C13—C90.4 (5)C5—C6—C1—C255.9 (4)
C7—N1—C13—C14179.3 (3)S1—C6—C1—C2176.0 (3)
N1—C13—C9—C80.9 (5)C16—C15—C20—C1954.5 (5)
C14—C13—C9—C8−177.9 (3)C14—C15—C20—C19179.6 (3)
N1—C13—C9—C10−176.4 (3)C20—C15—C16—C17−55.8 (5)
C14—C13—C9—C104.8 (5)C14—C15—C16—C17178.7 (3)
O1—C8—C9—C13179.0 (3)C6—C1—C2—C3−58.1 (5)
N2—C8—C9—C13−1.2 (5)C6—C5—C4—C354.0 (5)
O1—C8—C9—C10−3.6 (5)C19—C18—C17—C16−53.6 (5)
N2—C8—C9—C10176.2 (3)C15—C16—C17—C1855.8 (5)
C13—C9—C10—C11112.6 (4)C15—C20—C19—C18−53.5 (5)
C8—C9—C10—C11−64.7 (4)C17—C18—C19—C2052.6 (5)
C13—C9—C10—C12−121.1 (4)C1—C2—C3—C457.6 (5)
C8—C9—C10—C1261.7 (5)C5—C4—C3—C2−55.7 (5)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.861.912.761 (4)170
C11—H11C···O10.962.533.115 (5)119
Symmetry codes: (i) −x, −y, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.861.912.761 (4)170
C11—H11C···O10.962.533.115 (5)119
Symmetry codes: (i) −x, −y, −z+1.
Acknowledgements top

This work was supported by a fund from the National Natural Science Foundation of China (grant No. 30560179).

references
References top

Bruker (1998). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

Ettorre, A., Mai, A., Artico, M., Massa, S., De Montis, A. & La Colla, P. (1996). Acta Cryst. C52, 2115–2117.

Ettorre, A., Mai, A., Sbardella, G., Artico, M., La Colla, P. & Massa, S. (1998). Z. Kristallogr. New Cryst. Struct. 213, 593–595.

He, Y. P., Chen, F. E., Yu, X. J., Wang, Y. P., de Clercq, E., Balzarini, J. & Pannecouque, C. (2004). Bioorg. Chem. 32, 536–548.

Rao, Z.-K., Zhang, S.-S., He, Y.-P., Zheng, Y.-T. & Li, C. (2007). Acta Cryst. E63, o3942.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.