Received 30 November 2012
True symmetry or pseudosymmetry: 5-amino-1-(4-methylphenylsulfonyl)-4-pyrazolin-3-one and a comparison with its 1-phenylsulfonyl analogue
The title compound, C10H11N3O3S, (I), crystallizes as the NH tautomer. The two rings subtend an interplanar angle of 72.54 (4)°. An intramolecular hydrogen bond is formed from the NH2 group to a sulfonyl O atom. The molecular packing involves layers of molecules parallel to the bc plane at x 0, 1 etc., with two classical linear hydrogen bonds (amino-sulfonyl and pyrazoline-carbonyl N-HO) and a further interaction (amino-sulfonyl N-HO) completing a three-centre system with the intramolecular contact. The analogous phenyl derivative, (II) [Elgemeie, Hanfy, Hopf & Jones (1998). Acta Cryst. C54, 136-138], crystallizes with essentially the same unit cell and packing pattern, but with two independent molecules that differ significantly in the orientation of the phenyl groups. The space group is P21/c for (I) but P21 for (II), which is thus a pseudosymmetric counterpart of (I).
Recent reports from our laboratory have demonstrated the effectiveness of a variety of N-sulfonylated heterocycles and other antimetabolites as antiplastic agents in a number of experimental murine tumour systems (Elgemeie & Sood, 2006; Elgemeie et al., 2009). These compounds have been shown to cause inhibition of thymidine and uridine incorporation into DNA and RNA, and appear to constitute a new class of antimetabolites (Elgemeie et al., 2007). It was of interest to study their stereostructures and evaluate the effects of various structural modifications on their biological activity. Recently, some of our synthesized N-sulfonylated pyrazoles proved to be inhibitors of the enzyme cathepsin B (Myers et al., 2007). Members of this class, along with functional group analogues, were synthesized in an effort to define the structural requirements for activity. We report here the synthesis and structure of the title compound, (I), an N-sulfonated pyrazole obtained by intramolecular cyclization of N'-(2-cyanoacetyl)-4-methylbenzenesulfonohydrazide. Some time ago, we reported the structure of the corresponding 1-phenyl derivative, (II) (Elgemeie et al., 1998).
Compound (I) can potentially exist in a different tautomeric (hydroxy) form. However, spectroscopic studies indicated the presence of the NH tautomer in solution (e.g. the 13C NMR signal at 172.65 p.p.m. indicates a carbonyl C atom rather than a C-OH group). X-ray analysis (Fig. 1) establishes the exclusive presence of the ketonic form in the solid state; all H atoms could be located unambiguously, and bond lengths are also consistent with the NH form. Molecular dimensions (Table 1) may be regarded as normal. Atoms N2 and N3 are pyramidally coordinated; they lie 0.31 (1) and 0.21 (1) Å, respectively, out of the plane of their three substituents. The pyrazoline ring is reasonably planar (r.m.s. deviation = 0.04 Å), although its largest absolute torsion angle is N1-N2-C3-C4, -10.30 (11)°. The two rings subtend an interplanar angle of 72.54 (4)°, and their orientation is further described by the torsion angles C12-C11-S1-O2 = -0.31 (11)° and N2-N1-S1-O3 = -179.59 (7)°. In other words, C12-C11 is synperiplanar to S1-O2, and N1-N2 is antiperiplanar to S1-O3. An intramolecular N3-H03AO3 hydrogen bond is observed, albeit with a narrow angle of 116.6 (14)° at the H atom; at N3, atoms H03A and H03B lie out of the plane (of the pyrazoline ring plus N3) by 0.28 (2) and 0.25 (2) Å, respectively, both in the opposite direction to atom O3.
The molecular packing of (I) involves thick layers of molecules parallel to the bc plane at x 0, 1 etc. (Fig. 2); the tolyl groups project into the space between the layers (Fig. 3). In the order shown in Table 2, hydrogen bond 1 forms eight-membered rings of the common graph set R22(8) (Bernstein et al., 1995) over an inversion centre, hydrogen bonds 2 and 3 form a three-centre system (2 is the intramolecular hydrogen bond mentioned above), and hydrogen bond 4 connects the R22(8) rings in the direction of the diagonals  and . We note that the H03BO2ii [symmetry code: (ii) x, -y + , z + ] contact of 2.76 (2) Å would complete a bifurcated hydrogen-bond system with hydrogen bond 3, but we regard it as too long.
Several years ago, we published the structure of the phenyl analogue, (II), of (I) (Elgemeie et al., 1998). The unit cells are strikingly similar, except that the a axis of (II) is around 1.2 Å shorter [for (II): a = 10.7794 (19), b = 7.8301 (8) and c = 11.8317 (12) Å, and = 97.505 (8)°, at 173 K]. The space group of (II) was originally thought to be P21/c, but a more detailed analysis showed that the true space group was P21. The packing diagram of (II) is shown in Fig. 4. The two independent molecules in the asymmetric unit, which are related to each other by a local inversion centre, differ significantly in the orientation of the phenyl rings (Fig. 5), with torsion angles N1-S1-C11-C12 = 109.5 (3) and -73.0 (3)°. The two independent molecules of (II) form an exactly equivalent set of hydrogen bonds to each other and to (I), so that the packing pattern is topologically the same in both structures. Compound (II) is thus a pseudosymmetric counterpart of (I). The absence of the methyl group leads to the shorter a axis in (II).
| || Figure 1 |
The molecular structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The dashed line indicates the intramolecular N-HO hydrogen bond.
| || Figure 2 |
A packing diagram for (I), viewed parallel to the a axis. For clarity, the tolyl rings are reduced to the ipso-C atom, and all H atoms not involved in hydrogen bonding have also been omitted. Hydrogen bonds are indicated by thick (two-centre) or thin dashed lines (three-centre) and are numbered according to their order in Table 2.
| || Figure 3 |
A packing diagram for (I), viewed parallel to the b axis. Dashed lines indicate hydrogen bonds.
| || Figure 4 |
A packing diagram for (II) (Elgemeie et al., 1998), viewed parallel to the a axis. The first independent molecule is drawn with full bonds and the second with open bonds. For clarity, phenyl rings are reduced to the ipso-C atom, and all H atoms not involved in hydrogen bonding have also been omitted. Hydrogen bonds are indicated by thick (two-centre) or thin dashed lines (three-centre) and are numbered analogously to those of (I) in Table 2, with an additional `a' for those with the donor in molecule 1 and `b' for those with the donor in molecule 2. The origin has been shifted along the b axis to be consistent with Fig. 2, but not along the c axis, where it would be shifted by with respect to (I).
| || Figure 5 |
A least-squares fit of the two molecules of (II). The r.m.s. deviation for all atoms except the non-ipso atoms of the phenyl ring is 0.06 Å. Molecule 1 (unprimed atoms) was inverted and is shown with dashed bonds.
Compound (I) was obtained by refluxing an ethanolic solution (30 ml) of N'-(2-cyanoacetyl)-4-methylbenzenesulfonohydrazide (2.53 g, 0.01 mol) containing a few drops of piperidine for 1 h. After cooling, the precipitate, (I), was filtered off and recrystallized from ethanol (yield 87%; m.p. 500 K). IR (KBr, , cm-1): 3550, 3500, 3420 (NH2, NH), 1630 (C=O, s); 1H NMR (DMSO): 2.34 (s, 3H, CH3), 4.48 (s, 1H, CH), 6.88 (s, br, 2H, NH2), 7.41-7.92 (m, 4H, C6H4); MS, m/z = 253. Elemental analysis calculated for C10H11N3O3S: C 47.42, H 4.37, N 16.59, O 18.95, S 12.66%; found: C 47.66, H 4.47, N 16.62, O 19.18, S 12.71%.
The N-bound H atoms were refined freely. The methyl group was refined as an idealized rigid group [C-H = 0.98 Å and H-C-H = 109.5°; Uiso(H) = 1.5Ueq(C)] allowed to rotate but not tip; slow convergence of this group may indicate some degree of rotational disorder. Other H atoms were included using a riding model starting from calculated positions [C-H = 0.95 Å and Uiso(H) = 1.2Ueq(C)].
Data collection: CrysAlis PRO (Oxford Diffraction, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: SHELXL97.
Supplementary data for this paper are available from the IUCr electronic archives (Reference: FA3297 ). Services for accessing these data are described at the back of the journal.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.
Elgemeie, G. H., Elghandour, A. H. & Abd Elaziz, G. W. (2007). Synth. Commun. 37, 2827-2834.
Elgemeie, G. E. H., Hanfy, N., Hopf, H. & Jones, P. G. (1998). Acta Cryst. C54, 136-138.
Elgemeie, G. H. & Sood, S. A. (2006). Synth. Commun. 36, 743-753.
Elgemeie, G. H., Zaghary, W. A., Amin, K. A. & Nasr, T. M. (2009). J. Carbohydr. Chem. 28, 161-170.
Myers, M. C., Napper, A. D., Motlekar, N., Shah, P. P., Chiu, C.-H., Beavers, M. P., Diamond, S. L., Huryn, D. M. & Smith, A. B. III (2007). Bioorg. Med. Chem. Lett. 17, 4761-4766.
Oxford Diffraction (2011). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, Oxfordshire, England.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.
Siemens (1994). XP. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.