Abstract
C20H28N2OS, triclinic, P1̄ (no. 2), a = 6.7356(10) Å, b = 10.8739(15) Å, c = 13.245(2) Å, α = 75.580(7)°, β = 78.612(7)°, γ = 87.564(7)°, V = 921.0(2) Å3, Z = 2, R gt(F) = 0.0796, wR ref(F 2) = 0.2666, T = 100(2) K.
The molecular structure is shown in the figure. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.
Data collection and handling.
| Crystal: | Colourless needle |
| Size: | 0.51 × 0.08 × 0.05 mm |
| Wavelength: | MoKα radiation (0.71073 Å) |
| μ: | 0.19 mm−1 |
| Diffractometer, scan mode: | Bruker Apex-II, φ and ω |
| θ max, completeness: | 25.7°, >99 % |
| N(hkl)measured, N(hkl)unique, R int: | 24,903, 3501, 0.088 |
| Criterion for I obs, N(hkl)gt: | I obs > 2σ(I obs), 2568 |
| N(param)refined: | 225 |
| Programs: | Bruker [1], Olex2 [2], Shelx [3, 4] |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).
| Atom | x | y | z | U iso*/U eq |
|---|---|---|---|---|
| C1 | 0.6504 (6) | 0.7110 (3) | 0.1087 (3) | 0.0295 (8) |
| C2 | 0.4749 (6) | 0.7794 (3) | 0.1273 (3) | 0.0300 (8) |
| H2A | 0.3475 | 0.7427 | 0.1308 | 0.036* |
| C3 | 0.4841 (6) | 0.9018 (3) | 0.1409 (3) | 0.0313 (8) |
| C4 | 0.6702 (6) | 0.9549 (4) | 0.1376 (3) | 0.0375 (9) |
| H4 | 0.6780 | 1.0384 | 0.1466 | 0.045* |
| C5 | 0.8436 (6) | 0.8840 (4) | 0.1209 (4) | 0.0416 (10) |
| H5 | 0.9705 | 0.9190 | 0.1209 | 0.050* |
| C6 | 0.8373 (6) | 0.7637 (4) | 0.1044 (3) | 0.0372 (9) |
| H6 | 0.9586 | 0.7179 | 0.0904 | 0.045* |
| C7 | 0.3023 (7) | 1.0913 (4) | 0.1615 (3) | 0.0404 (9) |
| H7A | 0.1639 | 1.1241 | 0.1664 | 0.061* |
| H7B | 0.3888 | 1.1413 | 0.0972 | 0.061* |
| H7C | 0.3545 | 1.0977 | 0.2241 | 0.061* |
| C8 | 0.7251 (5) | 0.4808 (3) | 0.1234 (3) | 0.0277 (8) |
| C9 | 0.9518 (6) | 0.3741 (3) | 0.2479 (3) | 0.0308 (8) |
| H9 | 0.9503 | 0.3052 | 0.2103 | 0.037* |
| C10 | 0.8594 (5) | 0.3181 (3) | 0.3673 (3) | 0.0278 (8) |
| C11 | 0.6540 (6) | 0.2550 (4) | 0.3782 (3) | 0.0349 (9) |
| H11A | 0.5608 | 0.3187 | 0.3457 | 0.042* |
| H11B | 0.6725 | 0.1870 | 0.3395 | 0.042* |
| C12 | 0.5605 (6) | 0.1984 (4) | 0.4948 (3) | 0.0370 (9) |
| H12 | 0.4267 | 0.1586 | 0.4996 | 0.044* |
| C13 | 0.7016 (6) | 0.0976 (4) | 0.5441 (3) | 0.0388 (9) |
| H13A | 0.7193 | 0.0286 | 0.5065 | 0.047* |
| H13B | 0.6417 | 0.0605 | 0.6196 | 0.047* |
| C14 | 0.9068 (6) | 0.1580 (4) | 0.5356 (3) | 0.0357 (9) |
| H14 | 0.9996 | 0.0918 | 0.5672 | 0.043* |
| C15 | 0.8783 (6) | 0.2623 (4) | 0.5960 (3) | 0.0366 (9) |
| H15A | 1.0109 | 0.3014 | 0.5915 | 0.044* |
| H15B | 0.8202 | 0.2256 | 0.6719 | 0.044* |
| C16 | 0.7355 (6) | 0.3634 (3) | 0.5472 (3) | 0.0351 (9) |
| H16 | 0.7163 | 0.4318 | 0.5866 | 0.042* |
| C17 | 0.8269 (6) | 0.4210 (3) | 0.4302 (3) | 0.0317 (8) |
| H17A | 0.9582 | 0.4622 | 0.4249 | 0.038* |
| H17B | 0.7351 | 0.4869 | 0.3992 | 0.038* |
| C18 | 1.0001 (6) | 0.2162 (4) | 0.4180 (3) | 0.0335 (8) |
| H18A | 1.1333 | 0.2548 | 0.4130 | 0.040* |
| H18B | 1.0217 | 0.1486 | 0.3790 | 0.040* |
| C19 | 0.5301 (6) | 0.3027 (4) | 0.5552 (3) | 0.0364 (9) |
| H19A | 0.4691 | 0.2660 | 0.6307 | 0.044* |
| H19B | 0.4371 | 0.3679 | 0.5245 | 0.044* |
| C20 | 1.1679 (6) | 0.4231 (4) | 0.2244 (3) | 0.0416 (10) |
| H20A | 1.2577 | 0.3529 | 0.2475 | 0.062* |
| H20B | 1.1754 | 0.4887 | 0.2626 | 0.062* |
| H20C | 1.2099 | 0.4594 | 0.1479 | 0.062* |
| N1 | 0.6358 (5) | 0.5907 (3) | 0.0843 (2) | 0.0308 (7) |
| H1 | 0.543 (7) | 0.591 (4) | 0.048 (4) | 0.046* |
| N2 | 0.8261 (5) | 0.4770 (3) | 0.2016 (2) | 0.0310 (7) |
| H2 | 0.829 (7) | 0.550 (5) | 0.218 (4) | 0.046* |
| O1 | 0.3020 (4) | 0.9610 (2) | 0.1570 (2) | 0.0385 (7) |
| S1 | 0.70211 (15) | 0.35278 (9) | 0.07474 (7) | 0.0347 (4) |
1 Source of materials
All chemicals and solvents were used as purchased without further purifications. The uncorrected melting point was determined using an electrothermal digital melting-point apparatus. The NMR spectra were recorded at room temperature in DMSO-d6 solution on a Bruker Avance 500 MHz NMR spectrometer. The title compound was prepared as follows: while stirring a solution of 1-(adamantan-1-yl)ethanamine hydrochloride (0.1 g, 0.55 mmol, 1.0 eq) in dichloromethane (DCM) (1.5 mL), Et3N (0.23 mL, 1.65 mmol, 3.0 eq) was added and followed with phenyl isothiocyanate (0.070 mL, 0.58 mmol, 1.05 eq) in DCM (1.0 mL) at 0 °C. After 14 h at room temperature, the reaction solution was diluted with H2O (3 mL) and DCM (5 mL). The organic layer was separated and concentrated to give crude residue which was then triturated with DCM/Pentane mixture (1:10, 20 mL) to afford the title compound, 1-(1-(adamantan-1-yl)ethyl)-3-(3-methoxyphenyl)thiourea as white color solid with 83 % yield (143 mg, 0.45 mmol). The obtained compound was recrystallized from methanol. Melting point: 152–154 °C. 1 H-NMR (500 MHz, DMSO-d6): δ 1.00 (d, 3H, J = 7.0 Hz), 1.50–1.53 (6H, m, adamantane-H), 1.60–1.69 (6H, m, adamantane-H), 1.97 (3H, bs, adamantane-H), 3.73 (3H, s, OCH3), 4.19 (1H, bt, J = 7.0 Hz), 6.64 (1H, dd, J = 2.0, 8.0 Hz), 7.01 (1H, dd, J = 1.0, 8.0 Hz), 7.19 (1H, bdd, J = 8.0, 8.5 Hz), 7.34 (1H, bs, NH), 7.42 (1H, bd, J = 9.5 Hz), 9.442 (1H, s, NH). 13 C-NMR (125 MHz, DMSO-d6); δ 13.8, 27.82, 36.66, 38.23, 55.09, 57.31, 107.87, 109.17, 114.36, 129.26, 140.98, 153.1, 180.02.
2 Experimental details
Single crystal of C20H28N2OS was obtained through crystallization of the pure compound from slow evaporation of methanol. The collected frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. Data correction was performed for absorption effects using the multi-scan method (SADABS). The structure was solved and refined using the Bruker Shelx [3] software package. Using Olex2 [2], the structure was further refined with the ShelXL [4] refinement package. All H atoms bonded to C atoms were refined as riding, with C–H distances of 0.93 Å (for aromatic ring).
3 Comment
The discovery of the adamantine and rimantadine (the superior one) as the first adamantane-based antiviral drugs [5, 6], has sparked the research and development of diverse entities that contain adamantane moiety. The adamantane nucleus has been proven to be lipophilic bullet in many approved drugs [7]. Adamantane containing compounds are still rising in the medicinal chemistry area with wide biological indications [8], [9], [10], [11], [12]. Thiourea derivatives, on the other hand, are well known for their biological activities in different areas of medicinal chemistry. The thiourea derivative sorafenib and regorafenib are marketed as anticancer drugs [13], anti-ad activity [14], and antibiotic [15]. As an ongoing program to investigate new hybrid systems with potential bioactivity [16, 17] we are focusing on the hybridization of rimantadine with the thiourea moiety via the reaction of the commercially available rimantadine hydrochloride to generate the new hybrid system.
The crystallographic measurement shows that the crystal structure consists of the C20H28N2OS monomeric molecules. The asymmetric unit shows one molecular unit, in which all bond lengths and angles are in normal ranges [18]. The molecules maintain the trans-cis configuration [19] with respect to the position of the phenyl group relative to the thiono S1 atom across N1–C1 and N2–C9 bonds, respectively. The thiourea moiety (S1/N1/N2/C8) is essentially planar with a maximum deviation of 0.007(3) Å for atom C8 from the least square plane. It makes dihedral angle with phenyl ring of 51.762(15)°.
The molecular packing of the title compound is affected by N1–H1⋯S1 intermolecular hydrogen bond, with distance equal to 2.495 Å, to form centrosymmetric dimers along c axis. An additional C5–H5⋯O1 (−1 + x, +y, +z) intermolecular hydrogen bond is observed with distance equal to 2.457 Å.
Funding source: University of Sharjah
Award Identifier / Grant number: 23021440137
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Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: This research work was funded by University of Sharjah, for financial support (grant No. 23021440137). Part of this work has been carried out during sabbatical leave granted to MAK from the University of Jordan during the academic year 2021–2022.
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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