Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270101020571/sk1525sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270101020571/sk1525Isup2.hkl |
CCDC reference: 182995
2-Oxo-2-phenyl-thioacetamides were prepared according to literature methods (Asinger & Gentz, 1963). The combinatorial library was generated using an Argonaut first mate synthesiser with reaction components, aldehyde (0.15 mmol), ammonium acetate (0.15 mmol), 2-oxo-2-aryl-thioacetamide (0.15 mmol) loaded into each reaction vessel with 2 ml of C2H5OH. The library was heated for 12 h, cooled and products precipitated with 1M HCl (5 ml), filtered, dried, to give average library purity and yield of 78% and 63%. An identical library was generated using microwave irradiation to give average library purity and yield of 76% and 67%.
An alternative but conventional synthesis for [2-(3-nitrophenyl)-5-phenyl-1H-imidazol-4-yl]sulfanyl]acetic acid ethyl ester is as follows: A mixture of 2-oxo-2-phenyl-thioacetamide (1.04 g, 6.3 mmol), sodium carbonate (0.67 g, 6.3 mmol), ammonium acetate (0.59 g, 6.3 mmol), ethyl bromoacetate (1.05 g, 6.3 mmol) and 3-nitrobenzaldehyde (0.95 g, 6.3 mmol) in ethanol (50 ml) was heated under reflux for 7 h under nitrogen. The reaction mixture was concentrated to half its volume and an orange/yellow solid precipitated. Further purification using dry flash chromatography on silica gel with a gradient of ether:hexane:methanol (2:8:1) to (8:2:1) gave the pure product (1.59 g, 78%): m.p. 462 - 464 K:
Orange crystals were obtained by slow evaporation of a methanol solution. Uv-Vis λmax = 281, 315 nm. IR, (νC═O cm-1), 1728 (KBr). 1H NMR data (300 MHz) (δ, d6 DMSO), 1.07 (t, 3H), 3.82 (s, 2H), 3.95 (q, 2H), 7.37 (m, 1H), 7.48 (m, 2H), 7.80 (m, 1H), 7.90 (m, 2H), 8.24 (m, 1H), 8.47 (m, 1H), 8.92 (m, 1H). HRMS calc. 383.0940, found 383.0932. Anal. calc. for C19H17N3O4S, C. 59.58: H, 4.47: N, 10.97: S, 8.37: Found C. 59.39: H, 4.39: N, 10.92: S, 8.87.
In (I), all H atoms bound to C were treated as riding, with the SHELXL97 (Sheldrick, 1997) defaults for C—H lengths and with Uiso(H) = 1.5Ueq(C) for methylene H atoms, 1.2Ueq(C) for the remainder. Examination of the structure with PLATON (Spek, 1998) showed that there were no solvent accessible voids in the crystal lattice.
Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS (Siemens, 1994); data reduction: XSCANS (Siemens, 1994); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1998); software used to prepare material for publication: SHELXL97 and PREP8 (Ferguson, 1998).
C19H17N3O4S | F(000) = 800 |
Mr = 383.42 | Dx = 1.406 Mg m−3 |
Monoclinic, P21/n | Melting point: 463 K |
Hall symbol: -P 2yn | Mo Kα radiation, λ = 0.71073 Å |
a = 10.5606 (13) Å | Cell parameters from 70 reflections |
b = 12.1254 (9) Å | θ = 5.4–15.6° |
c = 14.8196 (10) Å | µ = 0.21 mm−1 |
β = 107.389 (6)° | T = 292 K |
V = 1810.9 (3) Å3 | Block, orange |
Z = 4 | 0.45 × 0.35 × 0.18 mm |
Bruker-AXS P4 diffractometer | Rint = 0.016 |
Radiation source: X-ray tube | θmax = 26.0°, θmin = 2.1° |
Graphite monochromator | h = −1→13 |
ω scans | k = −1→14 |
4517 measured reflections | l = −18→17 |
3524 independent reflections | 4 standard reflections every 296 reflections |
2569 reflections with I > 2σ(I) | intensity decay: variation 1% |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.042 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.110 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0496P)2 + 0.459P] where P = (Fo2 + 2Fc2)/3 |
3524 reflections | (Δ/σ)max < 0.001 |
245 parameters | Δρmax = 0.21 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
C19H17N3O4S | V = 1810.9 (3) Å3 |
Mr = 383.42 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 10.5606 (13) Å | µ = 0.21 mm−1 |
b = 12.1254 (9) Å | T = 292 K |
c = 14.8196 (10) Å | 0.45 × 0.35 × 0.18 mm |
β = 107.389 (6)° |
Bruker-AXS P4 diffractometer | Rint = 0.016 |
4517 measured reflections | 4 standard reflections every 296 reflections |
3524 independent reflections | intensity decay: variation 1% |
2569 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.110 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.21 e Å−3 |
3524 reflections | Δρmin = −0.18 e Å−3 |
245 parameters |
Geometry. Mean plane data ex-SHELXL97 for molecule (I) ############################################ Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane) -1.3989(0.0116)x + 11.9754(0.0025)y + 1.7733(0.0141)z = 1.8670(0.0113) * -0.0037 (0.0016) C31 * -0.0001 (0.0018) C32 * 0.0043 (0.0019) C33 * -0.0049 (0.0018) C34 * 0.0010 (0.0018) C35 * 0.0032 (0.0017) C36 - 0.0254 (0.0048) S1 0.1798 (0.0067) C11 0.0341 (0.0064) C21 - 0.0037 (0.0016) C31 Rms deviation of fitted atoms = 0.0033 -1.1984(0.0095)x + 11.9941(0.0022)y + 1.8194(0.0128)z = 2.0286(0.0057) Angle to previous plane (with approximate e.s.d.) = 1.21 (4) * -0.0026 (0.0015) C21 * 0.0024 (0.0014) C22 * 0.0011 (0.0015) C23 * -0.0044 (0.0016) C24 * 0.0041 (0.0017) C25 * -0.0006 (0.0016) C26 - 0.1222 (0.0057) S1 0.0557 (0.0060) C11 - 0.0026 (0.0015) C21 - 0.0279 (0.0058) C31 Rms deviation of fitted atoms = 0.0029 -1.3645(0.0110)x + 11.9640(0.0026)y + 1.9689(0.0157)z = 1.9828(0.0077) Angle to previous plane (with approximate e.s.d.) = 0.97 (4) * -0.0024 (0.0012) C1 * 0.0024 (0.0012) C2 * 0.0036 (0.0012) C3 * 0.0000 (0.0012) N1 * -0.0037 (0.0012) N2 - 0.0265 (0.0033) S1 0.1519 (0.0044) C11 0.0077 (0.0035) C21 0.0348 (0.0036) C31 Rms deviation of fitted atoms = 0.0028 -1.3989(0.0116)x + 11.9754(0.0025)y + 1.7733(0.0141)z = 1.8670(0.0113) Angle to previous plane (with approximate e.s.d.) = 0.87 (5) * -0.0037 (0.0016) C31 * -0.0001 (0.0018) C32 * 0.0043 (0.0019) C33 * -0.0049 (0.0018) C34 * 0.0010 (0.0018) C35 * 0.0032 (0.0017) C36 - 0.0254 (0.0048) S1 0.1798 (0.0067) C11 0.0341 (0.0064) C21 - 0.0037 (0.0016) C31 Rms deviation of fitted atoms = 0.0033 -0.1379(0.0212)x + 12.1129(0.0023)y + 0.6731(0.0477)z = 2.3016(0.0106) Angle to previous plane (with approximate e.s.d.) = 7.26 (6) * 0.0000 (0.0000) N23 * 0.0000 (0.0000) O21 * 0.0000 (0.0000) O22 0.0172 (0.0080) C23 - 0.1330 (0.0163) C21 Rms deviation of fitted atoms = 0.0000 |
x | y | z | Uiso*/Ueq | ||
S1 | 0.18564 (5) | 0.09268 (5) | 0.55909 (4) | 0.04748 (18) | |
O1 | 0.12588 (18) | −0.06314 (14) | 0.38695 (11) | 0.0589 (4) | |
O2 | 0.00941 (17) | 0.06410 (15) | 0.28649 (11) | 0.0646 (5) | |
C11 | 0.0745 (2) | 0.11400 (19) | 0.44312 (15) | 0.0453 (5) | |
C12 | 0.0764 (2) | 0.0267 (2) | 0.37148 (15) | 0.0443 (5) | |
C13 | −0.0079 (4) | −0.0100 (3) | 0.20684 (18) | 0.0947 (11) | |
C14 | −0.0799 (5) | 0.0444 (4) | 0.1220 (2) | 0.1380 (18) | |
C1 | 0.33841 (19) | 0.11568 (17) | 0.53746 (13) | 0.0357 (4) | |
N1 | 0.34275 (15) | 0.13124 (14) | 0.44714 (11) | 0.0384 (4) | |
C2 | 0.47011 (19) | 0.14464 (16) | 0.45516 (13) | 0.0357 (4) | |
N2 | 0.54564 (15) | 0.13775 (14) | 0.54627 (10) | 0.0389 (4) | |
C3 | 0.46281 (19) | 0.11972 (17) | 0.60215 (13) | 0.0361 (4) | |
C21 | 0.52093 (19) | 0.16416 (16) | 0.37448 (13) | 0.0355 (4) | |
C22 | 0.4301 (2) | 0.16912 (16) | 0.28463 (13) | 0.0374 (5) | |
C23 | 0.4771 (2) | 0.18528 (17) | 0.20842 (13) | 0.0400 (5) | |
C24 | 0.6102 (2) | 0.19680 (19) | 0.21716 (15) | 0.0476 (5) | |
C25 | 0.6989 (2) | 0.1928 (2) | 0.30645 (15) | 0.0509 (6) | |
C26 | 0.6554 (2) | 0.17621 (18) | 0.38473 (14) | 0.0443 (5) | |
N23 | 0.38144 (19) | 0.18805 (16) | 0.11352 (12) | 0.0484 (5) | |
O21 | 0.26298 (16) | 0.18710 (15) | 0.10629 (10) | 0.0619 (5) | |
O22 | 0.42414 (18) | 0.19232 (16) | 0.04549 (10) | 0.0687 (5) | |
C31 | 0.5123 (2) | 0.11105 (16) | 0.70503 (13) | 0.0371 (4) | |
C32 | 0.6466 (2) | 0.1199 (2) | 0.75322 (15) | 0.0522 (6) | |
C33 | 0.6920 (2) | 0.1111 (2) | 0.85078 (15) | 0.0610 (7) | |
C34 | 0.6052 (3) | 0.0926 (2) | 0.90191 (15) | 0.0548 (6) | |
C35 | 0.4727 (3) | 0.0844 (2) | 0.85609 (15) | 0.0562 (6) | |
C36 | 0.4260 (2) | 0.0936 (2) | 0.75863 (14) | 0.0502 (6) | |
H11A | −0.0150 | 0.1192 | 0.4478 | 0.054* | |
H11B | 0.0954 | 0.1843 | 0.4198 | 0.054* | |
H13A | 0.0781 | −0.0329 | 0.2025 | 0.114* | |
H13B | −0.0558 | −0.0753 | 0.2158 | 0.114* | |
H14A | −0.1685 | 0.0592 | 0.1235 | 0.207* | |
H14B | −0.0830 | −0.0018 | 0.0688 | 0.207* | |
H14C | −0.0366 | 0.1127 | 0.1165 | 0.207* | |
H2 | 0.6306 | 0.1435 | 0.5663 | 0.047* | |
H22 | 0.3396 | 0.1617 | 0.2762 | 0.045* | |
H24 | 0.6390 | 0.2069 | 0.1643 | 0.057* | |
H25 | 0.7890 | 0.2014 | 0.3143 | 0.061* | |
H26 | 0.7166 | 0.1731 | 0.4446 | 0.053* | |
H32 | 0.7069 | 0.1319 | 0.7195 | 0.063* | |
H33 | 0.7822 | 0.1178 | 0.8819 | 0.073* | |
H34 | 0.6364 | 0.0857 | 0.9673 | 0.066* | |
H35 | 0.4134 | 0.0726 | 0.8906 | 0.067* | |
H36 | 0.3353 | 0.0880 | 0.7284 | 0.060* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0363 (3) | 0.0709 (4) | 0.0383 (3) | −0.0029 (3) | 0.0159 (2) | −0.0012 (3) |
O1 | 0.0691 (11) | 0.0490 (10) | 0.0541 (9) | 0.0068 (9) | 0.0114 (8) | 0.0014 (8) |
O2 | 0.0725 (11) | 0.0719 (12) | 0.0425 (9) | 0.0189 (9) | 0.0068 (8) | 0.0026 (8) |
C11 | 0.0333 (11) | 0.0527 (14) | 0.0497 (12) | 0.0034 (10) | 0.0120 (9) | 0.0022 (10) |
C12 | 0.0366 (11) | 0.0546 (14) | 0.0414 (12) | −0.0014 (10) | 0.0110 (9) | 0.0036 (10) |
C13 | 0.119 (3) | 0.107 (3) | 0.0454 (15) | 0.024 (2) | 0.0050 (17) | −0.0149 (16) |
C14 | 0.173 (4) | 0.153 (4) | 0.0558 (19) | 0.043 (3) | −0.015 (2) | −0.008 (2) |
C1 | 0.0363 (10) | 0.0400 (11) | 0.0328 (9) | 0.0001 (9) | 0.0133 (8) | −0.0004 (8) |
N1 | 0.0359 (9) | 0.0482 (10) | 0.0319 (8) | −0.0008 (8) | 0.0110 (7) | 0.0020 (7) |
C2 | 0.0351 (10) | 0.0419 (11) | 0.0299 (9) | −0.0014 (9) | 0.0093 (8) | 0.0014 (8) |
N2 | 0.0316 (8) | 0.0548 (11) | 0.0302 (8) | −0.0063 (8) | 0.0090 (7) | 0.0018 (8) |
C3 | 0.0389 (10) | 0.0392 (11) | 0.0316 (9) | −0.0030 (9) | 0.0126 (8) | −0.0001 (8) |
C21 | 0.0382 (10) | 0.0382 (11) | 0.0313 (10) | −0.0002 (9) | 0.0124 (8) | 0.0030 (8) |
C22 | 0.0369 (10) | 0.0426 (12) | 0.0343 (10) | 0.0024 (9) | 0.0129 (8) | 0.0028 (8) |
C23 | 0.0470 (12) | 0.0426 (12) | 0.0305 (10) | 0.0074 (10) | 0.0114 (9) | 0.0068 (9) |
C24 | 0.0517 (13) | 0.0562 (14) | 0.0425 (12) | 0.0044 (11) | 0.0253 (10) | 0.0123 (10) |
C25 | 0.0390 (11) | 0.0668 (16) | 0.0508 (13) | −0.0020 (11) | 0.0193 (10) | 0.0096 (12) |
C26 | 0.0399 (11) | 0.0567 (14) | 0.0348 (10) | −0.0039 (10) | 0.0088 (9) | 0.0042 (10) |
N23 | 0.0563 (12) | 0.0564 (12) | 0.0325 (9) | 0.0135 (9) | 0.0131 (8) | 0.0062 (8) |
O21 | 0.0502 (10) | 0.0885 (14) | 0.0418 (9) | 0.0135 (9) | 0.0058 (7) | 0.0090 (8) |
O22 | 0.0795 (12) | 0.0984 (14) | 0.0324 (8) | 0.0168 (11) | 0.0232 (8) | 0.0084 (9) |
C31 | 0.0440 (11) | 0.0367 (11) | 0.0311 (9) | −0.0001 (9) | 0.0119 (8) | 0.0001 (8) |
C32 | 0.0463 (13) | 0.0725 (17) | 0.0371 (11) | −0.0034 (12) | 0.0114 (10) | 0.0023 (11) |
C33 | 0.0527 (14) | 0.0831 (19) | 0.0393 (12) | −0.0013 (13) | 0.0018 (10) | 0.0004 (12) |
C34 | 0.0726 (17) | 0.0595 (15) | 0.0291 (10) | 0.0036 (13) | 0.0102 (11) | −0.0010 (10) |
C35 | 0.0682 (16) | 0.0701 (17) | 0.0363 (11) | −0.0018 (13) | 0.0247 (11) | 0.0007 (11) |
C36 | 0.0473 (12) | 0.0700 (16) | 0.0357 (11) | −0.0007 (12) | 0.0163 (9) | 0.0004 (11) |
S1—C1 | 1.759 (2) | C31—C32 | 1.388 (3) |
S1—C11 | 1.787 (2) | C31—C36 | 1.393 (3) |
O1—C12 | 1.201 (3) | C32—C33 | 1.385 (3) |
O2—C12 | 1.326 (3) | C33—C34 | 1.371 (3) |
O2—C13 | 1.451 (3) | C34—C35 | 1.364 (3) |
N1—C1 | 1.366 (2) | C35—C36 | 1.384 (3) |
N1—C2 | 1.324 (2) | N2—H2 | 0.8600 |
N2—C2 | 1.350 (2) | C11—H11A | 0.9700 |
N2—C3 | 1.390 (2) | C11—H11B | 0.9700 |
C1—C3 | 1.376 (3) | C13—H13A | 0.9700 |
C2—C21 | 1.469 (3) | C13—H13B | 0.9700 |
C3—C31 | 1.460 (3) | C14—H14A | 0.9600 |
C11—C12 | 1.503 (3) | C14—H14B | 0.9600 |
C13—C14 | 1.422 (4) | C14—H14C | 0.9600 |
C21—C22 | 1.391 (3) | C22—H22 | 0.9300 |
C21—C26 | 1.390 (3) | C24—H24 | 0.9300 |
C22—C23 | 1.377 (3) | C25—H25 | 0.9300 |
C23—C24 | 1.379 (3) | C26—H26 | 0.9300 |
C23—N23 | 1.467 (3) | C32—H32 | 0.9300 |
C24—C25 | 1.375 (3) | C33—H33 | 0.9300 |
C25—C26 | 1.384 (3) | C34—H34 | 0.9300 |
N23—O22 | 1.222 (2) | C35—H35 | 0.9300 |
N23—O21 | 1.223 (2) | C36—H36 | 0.9300 |
C1—S1—C11 | 100.18 (9) | C35—C36—C31 | 121.1 (2) |
C12—O2—C13 | 117.6 (2) | S1—C11—H11A | 108.4 |
S1—C11—C12 | 115.70 (15) | S1—C11—H11B | 108.4 |
O1—C12—O2 | 124.7 (2) | C2—N2—H2 | 125.8 |
O1—C12—C11 | 126.9 (2) | C3—N2—H2 | 125.8 |
O2—C12—C11 | 108.31 (19) | O2—C13—H13A | 109.7 |
O2—C13—C14 | 109.6 (3) | O2—C13—H13B | 109.7 |
S1—C1—N1 | 120.12 (14) | C12—C11—H11A | 108.4 |
S1—C1—C3 | 127.98 (15) | C12—C11—H11B | 108.4 |
N1—C1—C3 | 111.90 (17) | C14—C13—H13A | 109.7 |
C1—N1—C2 | 105.05 (16) | C14—C13—H13B | 109.7 |
N1—C2—N2 | 111.27 (16) | C13—C14—H14A | 109.5 |
N1—C2—C21 | 123.72 (17) | C13—C14—H14B | 109.5 |
N2—C2—C21 | 125.01 (17) | C13—C14—H14C | 109.5 |
C2—N2—C3 | 108.46 (15) | H11A—C11—H11B | 107.4 |
C1—C3—N2 | 103.31 (16) | H13A—C13—H13B | 108.2 |
C1—C3—C31 | 133.95 (18) | H14A—C14—H14B | 109.5 |
N2—C3—C31 | 122.73 (17) | H14A—C14—H14C | 109.5 |
C2—C21—C22 | 118.09 (17) | H14B—C14—H14C | 109.5 |
C2—C21—C26 | 122.55 (17) | C21—C22—H22 | 120.8 |
C22—C21—C26 | 119.36 (18) | C23—C22—H22 | 120.8 |
C21—C22—C23 | 118.45 (18) | C23—C24—H24 | 121.0 |
C22—C23—C24 | 123.01 (19) | C25—C24—H24 | 121.0 |
C22—C23—N23 | 118.39 (19) | C24—C25—H25 | 119.6 |
C24—C23—N23 | 118.59 (18) | C26—C25—H25 | 119.6 |
C23—C24—C25 | 117.95 (19) | C21—C26—H26 | 119.7 |
C24—C25—C26 | 120.7 (2) | C25—C26—H26 | 119.7 |
C21—C26—C25 | 120.51 (19) | C31—C32—H32 | 119.6 |
O21—N23—O22 | 123.21 (18) | C33—C32—H32 | 119.6 |
O21—N23—C23 | 118.52 (17) | C32—C33—H33 | 119.7 |
O22—N23—C23 | 118.26 (19) | C34—C33—H33 | 119.7 |
C3—C31—C32 | 121.57 (18) | C33—C34—H34 | 120.2 |
C3—C31—C36 | 121.00 (18) | C35—C34—H34 | 120.2 |
C32—C31—C36 | 117.44 (18) | C34—C35—H35 | 119.8 |
C31—C32—C33 | 120.8 (2) | C36—C35—H35 | 119.8 |
C32—C33—C34 | 120.7 (2) | C31—C36—H36 | 119.4 |
C33—C34—C35 | 119.5 (2) | C35—C36—H36 | 119.4 |
C34—C35—C36 | 120.4 (2) | ||
C1—S1—C11—C12 | 70.19 (18) | C2—C21—C22—C23 | −178.78 (18) |
C13—O2—C12—O1 | 1.6 (4) | C21—C22—C23—C24 | 0.0 (3) |
C13—O2—C12—C11 | −176.5 (2) | C21—C22—C23—N23 | 178.66 (18) |
S1—C11—C12—O1 | 13.9 (3) | C22—C23—C24—C25 | −0.6 (3) |
S1—C11—C12—O2 | −168.09 (15) | N23—C23—C24—C25 | −179.3 (2) |
C12—O2—C13—C14 | −179.1 (3) | C23—C24—C25—C26 | 0.9 (4) |
C11—S1—C1—N1 | −6.30 (19) | C24—C25—C26—C21 | −0.5 (4) |
C11—S1—C1—C3 | 174.3 (2) | C22—C21—C26—C25 | −0.1 (3) |
C3—C1—N1—C2 | 0.2 (2) | C2—C21—C26—C25 | 179.0 (2) |
S1—C1—N1—C2 | −179.23 (15) | C22—C23—N23—O22 | −173.5 (2) |
C1—N1—C2—N2 | 0.2 (2) | C24—C23—N23—O22 | 5.3 (3) |
C1—N1—C2—C21 | −179.90 (18) | C22—C23—N23—O21 | 7.3 (3) |
N1—C2—N2—C3 | −0.6 (2) | C24—C23—N23—O21 | −174.0 (2) |
C21—C2—N2—C3 | 179.53 (19) | C1—C3—C31—C32 | −179.1 (2) |
N1—C1—C3—N2 | −0.6 (2) | N2—C3—C31—C32 | −0.3 (3) |
S1—C1—C3—N2 | 178.83 (15) | C1—C3—C31—C36 | 0.9 (4) |
N1—C1—C3—C31 | 178.3 (2) | N2—C3—C31—C36 | 179.6 (2) |
S1—C1—C3—C31 | −2.3 (4) | C36—C31—C32—C33 | 0.3 (3) |
C2—N2—C3—C1 | 0.7 (2) | C3—C31—C32—C33 | −179.8 (2) |
C2—N2—C3—C31 | −178.37 (19) | C31—C32—C33—C34 | 0.5 (4) |
N1—C2—C21—C26 | −178.9 (2) | C32—C33—C34—C35 | −0.9 (4) |
N2—C2—C21—C26 | 0.9 (3) | C33—C34—C35—C36 | 0.6 (4) |
N1—C2—C21—C22 | 0.2 (3) | C34—C35—C36—C31 | 0.1 (4) |
N2—C2—C21—C22 | −179.98 (19) | C32—C31—C36—C35 | −0.6 (3) |
C26—C21—C22—C23 | 0.4 (3) | C3—C31—C36—C35 | 179.5 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O21i | 0.86 | 2.46 | 3.058 (2) | 128 |
N2—H2···O1ii | 0.86 | 2.64 | 3.432 (3) | 153 |
C36—H36···S1 | 0.93 | 2.54 | 3.271 (2) | 136 |
Symmetry codes: (i) x+1/2, −y+1/2, z+1/2; (ii) −x+1, −y, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C19H17N3O4S |
Mr | 383.42 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 292 |
a, b, c (Å) | 10.5606 (13), 12.1254 (9), 14.8196 (10) |
β (°) | 107.389 (6) |
V (Å3) | 1810.9 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.21 |
Crystal size (mm) | 0.45 × 0.35 × 0.18 |
Data collection | |
Diffractometer | Bruker-AXS P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4517, 3524, 2569 |
Rint | 0.016 |
(sin θ/λ)max (Å−1) | 0.617 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.110, 1.03 |
No. of reflections | 3524 |
No. of parameters | 245 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.18 |
Computer programs: XSCANS (Siemens, 1994), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 1998), SHELXL97 and PREP8 (Ferguson, 1998).
S1—C1 | 1.759 (2) | N2—C2 | 1.350 (2) |
S1—C11 | 1.787 (2) | N2—C3 | 1.390 (2) |
O1—C12 | 1.201 (3) | C1—C3 | 1.376 (3) |
O2—C12 | 1.326 (3) | C2—C21 | 1.469 (3) |
O2—C13 | 1.451 (3) | C3—C31 | 1.460 (3) |
N1—C1 | 1.366 (2) | C11—C12 | 1.503 (3) |
N1—C2 | 1.324 (2) | C13—C14 | 1.422 (4) |
C1—S1—C11 | 100.18 (9) | N1—C2—C21 | 123.72 (17) |
S1—C11—C12 | 115.70 (15) | N2—C2—C21 | 125.01 (17) |
S1—C1—N1 | 120.12 (14) | C2—N2—C3 | 108.46 (15) |
S1—C1—C3 | 127.98 (15) | C1—C3—N2 | 103.31 (16) |
N1—C1—C3 | 111.90 (17) | C1—C3—C31 | 133.95 (18) |
C1—N1—C2 | 105.05 (16) | N2—C3—C31 | 122.73 (17) |
N1—C2—N2 | 111.27 (16) | ||
C1—S1—C11—C12 | 70.19 (18) | N1—C2—C21—C22 | 0.2 (3) |
S1—C11—C12—O2 | −168.09 (15) | C1—C3—C31—C36 | 0.9 (4) |
C11—S1—C1—N1 | −6.30 (19) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O21i | 0.86 | 2.46 | 3.058 (2) | 128 |
N2—H2···O1ii | 0.86 | 2.64 | 3.432 (3) | 153 |
C36—H36···S1 | 0.93 | 2.54 | 3.271 (2) | 136 |
Symmetry codes: (i) x+1/2, −y+1/2, z+1/2; (ii) −x+1, −y, −z+1. |
The development of high-throughput biological screening has lead to dramatic changes in the drug-discovery process. The generation of large numbers of new drug-like molecules has been achieved in a combinatorial manner rather than in a traditional sequential fashion. The exploitation of microwave irradiation for organic synthesis has gained in popularity with dramatic reduction in reaction times being reported for a wide range of organic reactions (Caddick, 1995; Strauss & Trainor, 1995; Galema, 1997). Clearly, the ability of microwave technology to rapidly synthesize organic compounds would be of significant benefit for combinatorial library generation and its potential as a future tool for drug-discovery programs has recently been identified (Larhed & Hallberg, 2001).
Substituted 4(5)-sulfanyl-imidazoles have been synthesized in a three-component reaction of an aldehyde, alkyl bromide, 2-oxo-thioacetamide and ammonium acetate. Parallel libraries have been generated using both conventional and a new microwave approaches: full synthetic details for compound (I), C19H17N3O4S, via both routes are described in the experimental section. The principal benefit of the microwave facilitated procedure over the conventional procedure was a reduction in the overall library generation time from 12 h to 16 minutes. The microwave library generation was achieved utilized an array of expandable reaction vessels which can accommodate the increased pressure during the reaction (Coleman et al., 2001).
The molecular structure of (I) is depicted with the atomic numbering scheme in Fig. 1, with selected geometric dimensions in Table 1. Bond lengths are in accord with the anticipated values (Orpen et al., 1994). Comparisons with a related monosubstituted 2-imidazol-2-yl derivative (Gallagher et al., 1998) indicate that the imidazolyl bond lengths expand slightly in (I) on extra substitution. A para-fluorophenyl acetamide analogue has been deposited as a private communication on the CSD (Gallagher et al., 2001).
In (I) the phenyl and meta-nitrophenyl C6 rings are essentially coplanar with the central imidazolyl ring, 0.87 (5) and 0.97 (4)°, respectively, resulting in an optimum conjugation in the system (–SCH2– moiety included, Figure 1): the λmax = 281 nm in CH3CN solution. Two principal intermolecular interactions are present in the crystal structure of (I) and both involve the imidazolyl N2—H2 donor as (i) the N2—H2···O21 interaction which generates a one-dimensional chain along [101] in combination with (ii) the longer N2—H2···O2i interaction which further impacts on the overall hydrogen bonding network by forming π···π stacked aromatic columns (where symmetry code: i = 1 - x,-y,1 - z) (Table 2).
Thus, the central imidazolyl ring core stacks about inversion centres along the b axis with the centroids Cg1···Cg1i 3.56 Å apart and a perpendicular separation of 3.36 Å (i = 1 - x,-y,1 - z) (Figure 2). For the three coplanar aromatic rings, the perpendicular stacking distance between planes is between 3.35 and 3.43 Å, with a dihedral angle between the stacked planes of < 2°. This is similar in nature to the π-π stacking in graphite where the interplanar spacing is 3.35 Å (Wells, 1984).
A search of the Cambridge Structural Database (Allen & Kennard, 1993) using CONQUEST version 1.2 (April 2001) for systems containing the 2-(3-nitrophenyl)-1H-imidazolyl group reveals eight structures, most of which contain two para-methoxyphenyl groups attached at the remaining two imidazolyl C atoms. Compound 4,5-bis(4-methoxyphenyl)-2-(3-nitrophenyl)-1H-imidazole, (II) CIZMUT01 (Inouye & Sakaino, 2000) is representative. From a series of solvates, different coloured crystals of (II) were obtained and the resulting bathochromic shifts explained by molecular planarity and charge transfer effects. A related search for the S—C3N2H moiety revealed six structures quite different to (I) where the sulfur has been incorporated in a heterocyclic ring or is part of a metal complex: a wider search for 2-thioimidazolyl, S—C3N2, yielded a total of 41 compounds. For comparison with (I) 1-benzyl-5-methoxycarbonylmethylthio-4-nitroimidazole, C13H13N3O4S, (Saadeh et al., 1995) contains imidC—S—Cester bond lengths of 1.740 and 1.799 Å, C—S—C 101.14° and C—S—C—C of -72.1 ° and similar to the data for (I) in Table 1. The related S—C—Cimid and S—C—Nimid angles are 134.8 and 122.0°.
Previous biological screening of substituted sulfanyl-imidazoles have shown their potential as acyl-CoA:cholesterol acyltransferase inhibitors, analgesic agents and angiotensin II receptor antagonists, (Higley et al., 1994; Sharpe et al., 1985; Deprez et al., 1995).