Abstract
C18H21N5O2, monoclinic, P21/c (no. 4), a = 10.0914(6) Å, b = 11.8919(7) Å, c = 15.545(1) Å, β = 102.321(6)°, V = 1822.5(2) Å3, Z = 4, R gt (F) = 0.0503, wR ref (F 2) = 0.1419, T = 293(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: | Yellow needle |
| Size: | 0.12 × 0.08 × 0.02 mm |
| Wavelength: | Mo Kα radiation (0.71073 Å) |
| μ: | 0.08 mm−1 |
| Diffractometer, scan mode: | Xcalibur, ω |
| θ max, completeness: | 29.5°, >99% |
| N(hkl)measured, N(hkl)unique, R int: | 27,507, 4593, 0.029 |
| Criterion for I obs, N(hkl)gt: | I obs > 2 σ(I obs), 2681 |
| N(param)refined: | 238 |
| Programs: | CrysAlisPRO [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 | 0.39788 (18) | 0.85662 (14) | 0.39620 (13) | 0.0678 (5) |
| C2 | 0.50765 (16) | 0.85408 (13) | 0.52762 (11) | 0.0571 (4) |
| C3 | 0.59947 (16) | 0.81652 (12) | 0.48078 (10) | 0.0546 (4) |
| C4 | 0.2893 (3) | 0.8728 (2) | 0.31574 (19) | 0.0961 (8) |
| H4A | 0.275 (2) | 0.801 (2) | 0.2832 (15) | 0.104 (7)* |
| H4B | 0.206 (4) | 0.889 (3) | 0.334 (2) | 0.177 (15)* |
| H4C | 0.313 (2) | 0.931 (2) | 0.2772 (17) | 0.124 (9)* |
| C5 | 0.5772 (2) | 0.78057 (17) | 0.31923 (12) | 0.0787 (5) |
| H5A | 0.6695 | 0.8077 | 0.3255 | 0.094* |
| H5B | 0.5231 | 0.8146 | 0.2666 | 0.094* |
| C6 | 0.57666 (16) | 0.65507 (15) | 0.30680 (10) | 0.0610 (4) |
| C7 | 0.6547 (2) | 0.6106 (2) | 0.25229 (14) | 0.0929 (7) |
| H7 | 0.7078 | 0.6580 | 0.2260 | 0.111* |
| C8 | 0.6548 (3) | 0.4979 (3) | 0.23653 (18) | 0.1177 (9) |
| H8 | 0.7054 | 0.4698 | 0.1978 | 0.141* |
| C9 | 0.5823 (3) | 0.4256 (2) | 0.27636 (17) | 0.1012 (7) |
| H9 | 0.5849 | 0.3487 | 0.2663 | 0.121* |
| C10 | 0.5061 (2) | 0.46734 (19) | 0.33090 (16) | 0.0926 (7) |
| H10 | 0.4561 | 0.4187 | 0.3585 | 0.111* |
| C11 | 0.50232 (19) | 0.58224 (17) | 0.34585 (14) | 0.0791 (6) |
| H11 | 0.4487 | 0.6101 | 0.3828 | 0.095* |
| C12 | 0.83549 (17) | 0.87279 (14) | 0.52832 (13) | 0.0686 (5) |
| H12A | 0.8435 | 0.8849 | 0.5909 | 0.082* |
| H12B | 0.8079 | 0.9429 | 0.4979 | 0.082* |
| C13 | 0.97004 (17) | 0.83487 (14) | 0.51051 (13) | 0.0692 (5) |
| H13A | 0.9623 | 0.8260 | 0.4476 | 0.083* |
| H13B | 1.0385 | 0.8915 | 0.5314 | 0.083* |
| C14 | 0.90817 (17) | 0.64230 (14) | 0.52541 (13) | 0.0652 (4) |
| H14A | 0.9360 | 0.5726 | 0.5565 | 0.078* |
| H14B | 0.8999 | 0.6287 | 0.4630 | 0.078* |
| C15 | 0.77311 (17) | 0.67826 (14) | 0.54216 (13) | 0.0662 (5) |
| H15A | 0.7051 | 0.6215 | 0.5204 | 0.079* |
| H15B | 0.7791 | 0.6872 | 0.6049 | 0.079* |
| C16 | 1.14421 (18) | 0.69196 (17) | 0.54303 (13) | 0.0743 (5) |
| H16A | 1.1727 | 0.6279 | 0.5811 | 0.089* |
| H16B | 1.2087 | 0.7521 | 0.5621 | 0.089* |
| C17 | 1.14980 (19) | 0.66082 (16) | 0.45276 (15) | 0.0742 (5) |
| C18 | 1.1442 (3) | 0.63501 (19) | 0.37957 (18) | 0.0970 (7) |
| H18 | 1.1398 | 0.6145 | 0.3213 | 0.116* |
| N1 | 0.38429 (14) | 0.87939 (12) | 0.47618 (11) | 0.0666 (4) |
| N2 | 0.52531 (14) | 0.81809 (11) | 0.39517 (9) | 0.0626 (4) |
| N3 | 0.53046 (17) | 0.87016 (12) | 0.62039 (10) | 0.0692 (4) |
| N4 | 0.73480 (13) | 0.78517 (10) | 0.49693 (9) | 0.0572 (3) |
| N5 | 1.01089 (13) | 0.72848 (11) | 0.55473 (9) | 0.0609 (4) |
| O1 | 0.64251 (15) | 0.84369 (13) | 0.66527 (8) | 0.0857 (4) |
| O2 | 0.44060 (16) | 0.91050 (15) | 0.65223 (10) | 0.1051 (5) |
Source of materials
The commercially available 2-methyl-4-nitro-1H-imidazole was reacted with benzyl chloride to produced 1-benzyl-2-methyl-4-nitro-1H-imidazole 1 [5]. Bromination of 1 with liquid bromine in DMF, in the presence potassium carbonate as a base afforded 1-benzyl-5-bromo-2-methyl-4-nitro-1H-imidazole 2 [5]. Reaction of 2 with piperazine using isopropanol as solvent gave 1-(1-benzyl-2-methyl-4-nitro-1H-imidazol-5-yl)piperazine 3 [5]. The title compound 4 has been prepared via reaction of the piperazine derivative 3 with propargyl bromide using NaH as base to produce the new compound 1-(N1-benzyl-2-methyl-4-nitro-imidazol-5-yl)-4-(prop-2-yn-1-yl) piperazine 4 as yellow flakes in 82% yield. M.p. = 122–124°. HRMS-ESI m/z: 362.15719 (M + Na)+. 1H NMR (500 MHz, DMSO-d 6, 298 K): δ 2.25 (s, 3H, H–C4); 2.46 (br.s, 4H, H–C13, H–C14); 2.99 (br.s, 4H, H–C12, H–C15); 3.17 (t, 1H, J = 2.2, H–C18); 3.28 (d, 2H, J = 2.2, H–C16); 5.17 (s, 2H, H–C5); 7.12 (d, 2H, J = 7.4 Hz, H–C7, H–C11); 7.32 (t, 1H, J = 7.3 Hz, H–C9); 7.39 (pseudo t, 2H, H–C8, H–C10). 13C NMR (125 MHz, DMSO-d 6, 298 K): δ 14.1 (C4); 46.2 (C5); 46.4 (C16); 48.5 (C12, C15); 51.4 (C13, C14); 76.3 (C17); 79.6 (C18); 126.9 (C7, C11); 128.1 (C9); 129.4 (C8, C10); 136.6 (C6); 138.8 (C2); 140.2 (C1); 140.9 (C3).
The chemicals were purchased from Aldrich (Germany), Fluka (Switzerland), and Scharlau; they were used without further purification. The NMR spectra were recorded on a Bruker Avance III-(500 MHz) spectrometer with tetramethylsilane (TMS) as an internal standard. 1H NMR (500 MHz), 13C-NMR (125 MHz), and 2D were recorded in Dimethylsulfoxide (DMSO-d 6). The following abbreviations are used to describe peak patterns: s = singlet, t = triplet, br.s = broad singlet. High-resolution mass spectra (HRMS) were measured (in positive/or negative ion mode) using the electrospray ion trap (ESI pos low mass) technique by collision-induced dissociation on a Bruker APEX-IV (7 Tesla) instrument. Melting points were determined on a Stuart (SMP-10) melting point apparatus.
Single crystal of C18H21N5O2 was obtained through crystallization of the pure compound from CHCl3/Et2O.
Experimental details
A suitable crystal was selected and mounted on a Xcalibur, Eos diffractometer. The crystal was kept at 293(2) K during data collection. Using Olex2 [2], the structure was solved with the ShelXT [3] structure solution program using Intrinsic Phasing and 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).
Comment
Imidazole is an important nucleus with diverse biological properties. The high therapeutic properties of the imidazole-related drugs have encouraged medicinal chemists to design and synthesize a large number of novel chemotherapeutic agents like Pantoprazole [6] (a proton pump inhibitor used for treatment of gastroesophageal reflux disease), Trifenagrel [7] (a potent arachidonate cyclooxygenase inhibitor), Eprosartan [8] (an angiotensin II receptor antagonist), and Cimetidine [9] (a histamine H2 receptor antagonist that inhibits stomach acid production). In view of the interest in the activity spectrum and profile of the nitroimidazoles and in continuation of our research on the synthesis and biological evaluation of imidazole analogs [10], [11], [12], [13], [14], [15], [16], [17], we here present the imidazolyl containing title structure. Herein, the propargyl bromide was couples with imidazole ring to produce the target compound.
This title crystal structure consists of the C18H21N5O2 molecules, in which all bond lengths are in normal ranges. The crystal is stabilized via CH⃛O (H18⃛O1 = 2.482(1) Å) and CH⃛O (H4A⃛O1 = 2.66(3) Å). The average plane of imidazole ring is perpendicular (90.17(7)°) to the average plane of the methylene groups of piperazine (C12–C13–C14–C15). A further intramolecular CH⃛O interactions can be also seen (H12A⃛O1 = 2.586(1) Å) and (H15B⃛O1 = 2.607(1) Å).
Funding source: Ministry of Higher Education, Jordan
Award Identifier / Grant number: Bas 1/1/2017
Acknowledgments
Part of this work has been carried out during sabbatical leave granted to RAA from the University of Jordan during the academic year 2020–2021.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: This study was financially supported by Scientific Research Support Fund/Ministry of Higher Education, Jordan (grant no. Bas 1/1/2017).
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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© 2021 Raed A. Al-Qawasmeh et al., published by De Gruyter, Berlin/Boston
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