Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802016902/ci6157sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536802016902/ci6157Isup2.hkl |
CCDC reference: 198970
The title compound was synthesized according to the procedure developed by Nagarajan et al. (1982). Expecting polymorphism, three crystalline samples of (I) were obtained from three different solvents, as follows: the title compound was dissolved in large volume of boiling acetone and the solution was concentrated, to obtain a crystalline product with melting point 458–459 K (sample 1). The second sample was obtained by dissolving 0.5 g of (I) in 1 ml of DMF on a water bath and leaving the solution at room temperature for several hours; the melting point of this sample was found to be the same as that of sample 1. To prepare the third sample, 0.5 g of (I) was dissolved in 1 ml of concentrated H2SO4 and 5 ml water, and the solution was set aside overnight. This sample was found to melt partially around 458 K, re-solidified at about 483 K and the melting was complete at about 493 K.
All the H atoms were positioned geometrically and were allowed to ride on their parent atoms with SHELXL97 (Sheldrick, 1997) defaults for bond lengths and displacement parameters. Owing to a reduction of the data-to-parameter ratio, the Friedel opposites were not merged during the refinement.
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1983, 1995).
C8H11N5O5S | F(000) = 600 |
Mr = 289.28 | Dx = 1.594 Mg m−3 |
Orthorhombic, Pna21 | Cu Kα radiation, λ = 1.5418 Å |
Hall symbol: P 2c -2n | Cell parameters from 25 reflections |
a = 7.046 (2) Å | θ = 13.8–29.6° |
b = 19.566 (6) Å | µ = 2.68 mm−1 |
c = 8.743 (2) Å | T = 293 K |
V = 1205.3 (6) Å3 | Bipyramidal, pale yellow |
Z = 4 | 0.2 × 0.13 × 0.1 mm |
Enraf-Nonius CAD-4 diffractometer | 1035 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.047 |
Graphite monochromator | θmax = 71.7°, θmin = 4.5° |
ω–2θ scans | h = −6→8 |
Absorption correction: ψ scan (XRAYACS; Chandrasekaran, 1998) | k = −24→19 |
Tmin = 0.616, Tmax = 0.775 | l = 0→10 |
1851 measured reflections | 3 standard reflections every 200 reflections |
1195 independent reflections | intensity decay: none |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.060 | w = 1/[σ2(Fo2) + (0.1053P)2 + 1.7101P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.176 | (Δ/σ)max < 0.001 |
S = 1.11 | Δρmax = 0.35 e Å−3 |
1851 reflections | Δρmin = −0.70 e Å−3 |
174 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
1 restraint | Extinction coefficient: 0.039 (4) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983) |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.01 (5) |
C8H11N5O5S | V = 1205.3 (6) Å3 |
Mr = 289.28 | Z = 4 |
Orthorhombic, Pna21 | Cu Kα radiation |
a = 7.046 (2) Å | µ = 2.68 mm−1 |
b = 19.566 (6) Å | T = 293 K |
c = 8.743 (2) Å | 0.2 × 0.13 × 0.1 mm |
Enraf-Nonius CAD-4 diffractometer | 1035 reflections with I > 2σ(I) |
Absorption correction: ψ scan (XRAYACS; Chandrasekaran, 1998) | Rint = 0.047 |
Tmin = 0.616, Tmax = 0.775 | 3 standard reflections every 200 reflections |
1851 measured reflections | intensity decay: none |
1195 independent reflections |
R[F2 > 2σ(F2)] = 0.060 | H-atom parameters constrained |
wR(F2) = 0.176 | Δρmax = 0.35 e Å−3 |
S = 1.11 | Δρmin = −0.70 e Å−3 |
1851 reflections | Absolute structure: Flack (1983) |
174 parameters | Absolute structure parameter: −0.01 (5) |
1 restraint |
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 taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used 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. |
x | y | z | Uiso*/Ueq | ||
S11 | 0.22430 (19) | 0.51346 (6) | 0.93204 (18) | 0.0436 (5) | |
N1 | 0.3458 (6) | 0.5728 (2) | 0.8425 (6) | 0.0439 (11) | |
C2 | 0.2862 (8) | 0.6022 (3) | 0.7047 (6) | 0.0398 (13) | |
N3 | 0.4245 (6) | 0.6487 (2) | 0.6630 (5) | 0.0437 (11) | |
C4 | 0.5590 (9) | 0.6603 (4) | 0.7892 (7) | 0.0595 (18) | |
H4A | 0.5269 | 0.7012 | 0.8464 | 0.071* | |
H4B | 0.6882 | 0.6641 | 0.7519 | 0.071* | |
C5 | 0.5327 (8) | 0.5965 (3) | 0.8856 (7) | 0.0531 (16) | |
H5A | 0.6287 | 0.5626 | 0.8620 | 0.064* | |
H5B | 0.5382 | 0.6072 | 0.9938 | 0.064* | |
C6 | 0.3955 (8) | 0.6972 (3) | 0.5510 (6) | 0.0383 (12) | |
N7 | 0.3511 (6) | 0.6816 (2) | 0.4047 (5) | 0.0382 (10) | |
C8 | 0.3372 (8) | 0.7440 (3) | 0.3314 (7) | 0.0427 (13) | |
C9 | 0.3752 (8) | 0.7935 (3) | 0.4383 (9) | 0.0502 (14) | |
H9 | 0.3754 | 0.8402 | 0.4189 | 0.060* | |
N10 | 0.4126 (7) | 0.7645 (2) | 0.5767 (6) | 0.0447 (12) | |
O12 | 0.3363 (7) | 0.4983 (2) | 1.0641 (5) | 0.0559 (11) | |
O13 | 0.1818 (7) | 0.4595 (2) | 0.8278 (6) | 0.0639 (13) | |
C14 | 0.0197 (9) | 0.5553 (4) | 0.9834 (9) | 0.0619 (18) | |
H14A | −0.0535 | 0.5652 | 0.8935 | 0.093* | |
H14B | 0.0514 | 0.5972 | 1.0345 | 0.093* | |
H14C | −0.0532 | 0.5269 | 1.0509 | 0.093* | |
O15 | 0.1403 (6) | 0.58986 (19) | 0.6366 (5) | 0.0539 (11) | |
C16 | 0.3506 (11) | 0.6123 (3) | 0.3401 (7) | 0.0544 (15) | |
H16A | 0.3131 | 0.6143 | 0.2347 | 0.082* | |
H16B | 0.2626 | 0.5843 | 0.3959 | 0.082* | |
H16C | 0.4755 | 0.5931 | 0.3477 | 0.082* | |
N17 | 0.2799 (7) | 0.7528 (3) | 0.1805 (7) | 0.0533 (13) | |
O18 | 0.2410 (9) | 0.7032 (3) | 0.1007 (6) | 0.0830 (17) | |
O19 | 0.2703 (9) | 0.8117 (3) | 0.1318 (8) | 0.0869 (17) |
U11 | U22 | U33 | U12 | U13 | U23 | |
S11 | 0.0571 (9) | 0.0384 (7) | 0.0352 (7) | −0.0023 (6) | −0.0032 (8) | 0.0036 (6) |
N1 | 0.040 (2) | 0.054 (3) | 0.038 (2) | −0.008 (2) | −0.006 (2) | 0.010 (2) |
C2 | 0.047 (3) | 0.042 (3) | 0.031 (3) | −0.007 (2) | −0.004 (3) | 0.009 (2) |
N3 | 0.047 (3) | 0.050 (3) | 0.034 (2) | −0.009 (2) | −0.003 (2) | 0.008 (2) |
C4 | 0.059 (4) | 0.080 (5) | 0.040 (3) | −0.024 (4) | −0.012 (3) | 0.017 (3) |
C5 | 0.047 (3) | 0.073 (4) | 0.039 (3) | −0.013 (3) | −0.013 (3) | 0.004 (3) |
C6 | 0.039 (3) | 0.043 (3) | 0.032 (3) | 0.003 (2) | 0.001 (2) | −0.002 (2) |
N7 | 0.049 (2) | 0.035 (2) | 0.031 (2) | 0.001 (2) | 0.000 (2) | −0.0011 (19) |
C8 | 0.045 (3) | 0.044 (3) | 0.039 (3) | −0.003 (3) | −0.001 (3) | 0.009 (3) |
C9 | 0.054 (3) | 0.040 (3) | 0.057 (4) | −0.003 (2) | 0.005 (4) | 0.004 (3) |
N10 | 0.059 (3) | 0.035 (2) | 0.040 (3) | −0.005 (2) | 0.002 (2) | −0.0029 (19) |
O12 | 0.066 (2) | 0.059 (2) | 0.042 (2) | 0.004 (2) | −0.011 (2) | 0.016 (2) |
O13 | 0.102 (3) | 0.039 (2) | 0.051 (3) | −0.015 (2) | −0.008 (3) | −0.007 (2) |
C14 | 0.046 (3) | 0.074 (4) | 0.065 (4) | 0.000 (3) | 0.004 (3) | 0.011 (4) |
O15 | 0.054 (2) | 0.054 (2) | 0.054 (3) | −0.0126 (19) | −0.018 (2) | 0.013 (2) |
C16 | 0.077 (4) | 0.046 (3) | 0.040 (3) | 0.003 (3) | −0.002 (3) | −0.008 (3) |
N17 | 0.055 (3) | 0.057 (3) | 0.048 (3) | 0.000 (3) | −0.003 (3) | 0.015 (3) |
O18 | 0.125 (5) | 0.075 (3) | 0.049 (3) | −0.014 (3) | −0.027 (3) | 0.007 (3) |
O19 | 0.114 (4) | 0.072 (3) | 0.075 (4) | 0.008 (3) | −0.018 (3) | 0.034 (3) |
S11—O12 | 1.430 (5) | C6—N7 | 1.351 (7) |
S11—O13 | 1.427 (4) | N7—C8 | 1.382 (7) |
S11—N1 | 1.641 (5) | N7—C16 | 1.468 (7) |
S11—C14 | 1.718 (7) | C8—C9 | 1.372 (9) |
N1—C2 | 1.400 (7) | C8—N17 | 1.391 (8) |
N1—C5 | 1.447 (7) | C9—N10 | 1.362 (9) |
C2—O15 | 1.212 (6) | C9—H9 | 0.93 |
C2—N3 | 1.381 (7) | C14—H14A | 0.96 |
N3—C6 | 1.380 (7) | C14—H14B | 0.96 |
N3—C4 | 1.472 (7) | C14—H14C | 0.96 |
C4—C5 | 1.518 (9) | C16—H16A | 0.96 |
C4—H4A | 0.97 | C16—H16B | 0.96 |
C4—H4B | 0.97 | C16—H16C | 0.96 |
C5—H5A | 0.97 | N17—O19 | 1.230 (7) |
C5—H5B | 0.97 | N17—O18 | 1.226 (7) |
C6—N10 | 1.341 (7) | ||
O12—S11—O13 | 118.5 (3) | N10—C6—N3 | 122.9 (5) |
O12—S11—N1 | 104.1 (3) | N7—C6—N3 | 123.4 (5) |
O13—S11—N1 | 109.2 (3) | C6—N7—C8 | 104.8 (4) |
O12—S11—C14 | 110.6 (3) | C6—N7—C16 | 125.0 (5) |
O13—S11—C14 | 110.1 (3) | C8—N7—C16 | 129.5 (4) |
N1—S11—C14 | 103.0 (3) | C9—C8—N7 | 107.1 (5) |
C2—N1—C5 | 111.4 (5) | C9—C8—N17 | 128.0 (6) |
C2—N1—S11 | 123.1 (4) | N7—C8—N17 | 124.8 (5) |
C5—N1—S11 | 125.3 (4) | N10—C9—C8 | 110.5 (5) |
O15—C2—N3 | 126.8 (5) | N10—C9—H9 | 124.8 |
O15—C2—N1 | 126.5 (5) | C8—C9—H9 | 124.8 |
N3—C2—N1 | 106.6 (5) | C6—N10—C9 | 104.0 (5) |
C6—N3—C2 | 122.4 (5) | S11—C14—H14A | 109.5 |
C6—N3—C4 | 121.4 (5) | S11—C14—H14B | 109.5 |
C2—N3—C4 | 111.0 (4) | H14A—C14—H14B | 109.5 |
N3—C4—C5 | 102.1 (5) | S11—C14—H14C | 109.5 |
N3—C4—H4A | 111.3 | H14A—C14—H14C | 109.5 |
C5—C4—H4A | 111.3 | H14B—C14—H14C | 109.5 |
N3—C4—H4B | 111.3 | N7—C16—H16A | 109.5 |
C5—C4—H4B | 111.3 | N7—C16—H16B | 109.5 |
H4A—C4—H4B | 109.2 | H16A—C16—H16B | 109.5 |
N1—C5—C4 | 103.3 (5) | N7—C16—H16C | 109.5 |
N1—C5—H5A | 111.1 | H16A—C16—H16C | 109.5 |
C4—C5—H5A | 111.1 | H16B—C16—H16C | 109.5 |
N1—C5—H5B | 111.1 | O19—N17—O18 | 122.2 (6) |
C4—C5—H5B | 111.1 | O19—N17—C8 | 117.4 (6) |
H5A—C5—H5B | 109.1 | O18—N17—C8 | 120.4 (5) |
N10—C6—N7 | 113.6 (5) | ||
O12—S11—N1—C2 | 179.6 (4) | C4—N3—C6—N10 | −30.3 (9) |
O13—S11—N1—C2 | 52.1 (5) | C2—N3—C6—N7 | −59.6 (8) |
C14—S11—N1—C2 | −64.9 (5) | C4—N3—C6—N7 | 148.3 (6) |
O12—S11—N1—C5 | 5.8 (6) | N10—C6—N7—C8 | −0.6 (6) |
O13—S11—N1—C5 | −121.8 (5) | N3—C6—N7—C8 | −179.3 (5) |
C14—S11—N1—C5 | 121.2 (6) | N10—C6—N7—C16 | 170.8 (6) |
C5—N1—C2—O15 | 176.4 (6) | N3—C6—N7—C16 | −7.9 (9) |
S11—N1—C2—O15 | 1.8 (9) | C6—N7—C8—C9 | 0.3 (6) |
C5—N1—C2—N3 | −4.5 (6) | C16—N7—C8—C9 | −170.5 (6) |
S11—N1—C2—N3 | −179.0 (4) | C6—N7—C8—N17 | −175.0 (5) |
O15—C2—N3—C6 | 13.0 (9) | C16—N7—C8—N17 | 14.1 (9) |
N1—C2—N3—C6 | −166.1 (5) | N7—C8—C9—N10 | −0.1 (7) |
O15—C2—N3—C4 | 167.7 (6) | N17—C8—C9—N10 | 175.1 (6) |
N1—C2—N3—C4 | −11.4 (6) | N7—C6—N10—C9 | 0.5 (7) |
C6—N3—C4—C5 | 176.5 (5) | N3—C6—N10—C9 | 179.2 (5) |
C2—N3—C4—C5 | 21.5 (7) | C8—C9—N10—C6 | −0.3 (7) |
C2—N1—C5—C4 | 17.5 (7) | C9—C8—N17—O19 | 4.0 (9) |
S11—N1—C5—C4 | −168.1 (5) | N7—C8—N17—O19 | 178.4 (6) |
N3—C4—C5—N1 | −22.4 (7) | C9—C8—N17—O18 | −176.0 (7) |
C2—N3—C6—N10 | 121.9 (6) | N7—C8—N17—O18 | −1.5 (9) |
D—H···A | D—H | H···A | D···A | D—H···A |
C14—H14A···O15 | 0.96 | 2.67 | 3.221 (9) | 117 |
C16—H16A···O18 | 0.96 | 2.16 | 2.853 (8) | 128 |
C16—H16B···O15 | 0.96 | 2.28 | 3.017 (8) | 133 |
C14—H14B···O18i | 0.96 | 2.53 | 3.443 (9) | 158 |
C5—H5B···O19ii | 0.97 | 2.58 | 3.265 (8) | 128 |
C9—H9···O13iii | 0.93 | 2.50 | 3.412 (7) | 168 |
C14—H14C···O15iv | 0.96 | 2.48 | 3.336 (8) | 148 |
C14—H14C···O13iv | 0.96 | 2.60 | 3.342 (9) | 134 |
Symmetry codes: (i) x, y, z+1; (ii) x+1/2, −y+3/2, z+1; (iii) −x+1/2, y+1/2, z−1/2; (iv) −x, −y+1, z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H11N5O5S |
Mr | 289.28 |
Crystal system, space group | Orthorhombic, Pna21 |
Temperature (K) | 293 |
a, b, c (Å) | 7.046 (2), 19.566 (6), 8.743 (2) |
V (Å3) | 1205.3 (6) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 2.68 |
Crystal size (mm) | 0.2 × 0.13 × 0.1 |
Data collection | |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | ψ scan (XRAYACS; Chandrasekaran, 1998) |
Tmin, Tmax | 0.616, 0.775 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1851, 1195, 1035 |
Rint | 0.047 |
(sin θ/λ)max (Å−1) | 0.616 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.060, 0.176, 1.11 |
No. of reflections | 1851 |
No. of parameters | 174 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.35, −0.70 |
Absolute structure | Flack (1983) |
Absolute structure parameter | −0.01 (5) |
Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1994), CAD-4 EXPRESS, XCAD4 (Harms & Wocadlo, 1996), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), ORTEP-3 (Farrugia, 1997), SHELXL97 and PARST (Nardelli, 1983, 1995).
D—H···A | D—H | H···A | D···A | D—H···A |
C14—H14A···O15 | 0.96 | 2.67 | 3.221 (9) | 117 |
C16—H16A···O18 | 0.96 | 2.16 | 2.853 (8) | 128 |
C16—H16B···O15 | 0.96 | 2.28 | 3.017 (8) | 133 |
C14—H14B···O18i | 0.96 | 2.53 | 3.443 (9) | 158 |
C5—H5B···O19ii | 0.97 | 2.58 | 3.265 (8) | 128 |
C9—H9···O13iii | 0.93 | 2.50 | 3.412 (7) | 168 |
C14—H14C···O15iv | 0.96 | 2.48 | 3.336 (8) | 148 |
C14—H14C···O13iv | 0.96 | 2.60 | 3.342 (9) | 134 |
Symmetry codes: (i) x, y, z+1; (ii) x+1/2, −y+3/2, z+1; (iii) −x+1/2, y+1/2, z−1/2; (iv) −x, −y+1, z+1/2. |
1-Substituted 5-nitroimidazoles exhibit antiprotozoal activity, while the 4-nitroimidazole derivatives do not. There are at least five 5-nitroimidazole antiprotozoal drugs on the market, namely metronidazole, secnidazole, ornidazole, nimorazole and dimetridazole. The title compound, (I), synthesized by Nagarajan et al. (1982) is reported to have antiamoebic activity (Nagarajan et al., 1982) and has been launched as a drug by Alkem Laboratories. Crystals of (I) were obtained from three different solvents, viz, boiling acetone (sample 1), DMF (sample 2) and H2SO4 (sample 3), in order to verify whether they yield any polymorphic substances, which have commercial value. Crystal structure and powder diffraction experiments showed that three sample preparations led to the same structure. Hence, the crystal structure of sample 2 alone is described below.
A perspective view of the molecule (I), including the atomic numbering, is shown in Fig. 1. The molecule contains an imidazolidine ring (A) and an imidazole ring (B) linked through a C—N bond. Ring A is twisted about the C4—C5 bond and the mean plane through this ring forms a dihedral angle of 49.0 (2)° with ring B. The methylsulfonyl group attached to ring A has a distorted tetrahedral geometry due to the widening of the O13—S11—O12 angle [118.5 (3)°]. This is caused by the repulsion between the lone pair orbitals of the two O atoms (Mckanna et al., 1982). The nitro group attached to the B ring is nearly coplanar with that ring, as is evident from the torsion angles C9—C8—N17—O19 [4.0 (9)°] and N7—C8—N17—O18 [−1.5 (9)°]. Weak C—H···O-type intramolecular hydrogen bonds are observed in the molecule and they are shown in Fig. 1.
In the crystal, face-to-face stacking (α = 5.3°) of the B ring and the B rings of glide-related molecules at (1/2 + x, 3/2 − y, z) and (−1/2 + x, 3/2 − y, z) are observed. These rings are stacked along the a axis, with their centroids separated by a distance of 3.564 (3) Å, indicating significant π–π interactions. The crystal structure is stabilized by these stacking interactions (Fig. 2) and also by several weak C—H···O hydrogen bonds (Table 1).