3-(1-Methyl-5-nitro­imidazol-2-yl)-1-(methyl­sulfonyl)­imidazolidin-2-one

In the title compound (satranidazole), C₈H₁₁N₅O₅S, the dihedral angle between the mean plane of the imidazolidine and imidazole rings is 49.0 (2)°. In the solid state, the imidazole rings of the glide-related mol­ecules are stacked along the a axis, with significant π–π interactions. The crystal structure is further stabilized by weak C—H...O intermolecular hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.009 Å
• R factor = 0.060
• wR factor = 0.176
• Data-to-parameter ratio = 10.6

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           71.70
         From the CIF: _reflns_number_total               1195
         TEST2: Reflns within _diffrn_reflns_theta_max
         Count of symmetry unique reflns         1269
         Completeness (_total/calc)             94.17%
          Alert C: < 95% complete

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           71.70
         From the CIF: _reflns_number_total               1195
         Count of symmetry unique reflns         1269
         Completeness (_total/calc)             94.17%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured         0
         Fraction of Friedel pairs measured     0.000
         Are heavy atom types Z>Si present          yes
          WARNING: Large fraction of Friedel related reflns may
                   be needed to determine absolute structure


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

---

S1. Comment

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).

S2. Experimental

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.

S3. Refinement

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.

Computing details

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).

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids and the atom-numbering scheme. Weak C—H···O intramolecular hydrogen bonds are also shown.
	Fig. 2. Stereoview showing the stacking interactions along a axis.

3-(1-Methyl-5-nitroimidazol-2-yl)-1-methylsulfonyl-imidazolidin-2-one

Crystal data

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) Å^3	Bipyramidal, pale yellow
Z = 4	0.2 × 0.13 × 0.1 mm

Data collection

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

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.060	w = 1/[σ^2(Fo^2) + (0.1053P)^2 + 1.7101P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 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+0.001xFc^2λ^3/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)

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	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)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

Geometric parameters (Å, º)

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)

Hydrogen-bond geometry (Å, º)

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···O18^i	0.96	2.53	3.443 (9)	158
C5—H5B···O19^ii	0.97	2.58	3.265 (8)	128
C9—H9···O13^iii	0.93	2.50	3.412 (7)	168
C14—H14C···O15^iv	0.96	2.48	3.336 (8)	148
C14—H14C···O13^iv	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.