Crystal structure of ethyl 2-(5-amino-1-benzenesulfonyl-3-oxo-2,3-dihydro-1H-pyrazol-2-yl)acetate

In the title compound, C13H15N3O5S, the two rings face each other in a ‘V′ form at the S atom, with one N—H⋯O=S and one C—H⋯O=S contact from the pyrazolyl substituents to the sulfonyl group. Two classical hydrogen bonds from the amine group, one of the form N—H⋯O=S and one N—H⋯O=Coxo, link the molecules to form layers parallel to the bc plane.


Chemical context
We are interested in the development of innovative synthetic strategies for N-sulfonyl-and N-sulfonylamino-based heterocyclic ring systems that have found application as new antimicrobial and anti-viral agents (Azzam et al., 2017Elgemeie et al., 2017Elgemeie et al., , 2019Zhu et al., 2013). Michael et al. (2007) investigated the inhibition capabilities of a novel series of our reported N-sulfonylpyrazoles (Elgemeie et al., 1998(Elgemeie et al., , 1999(Elgemeie et al., , 2013 towards the enzyme cathepsin B16. Shyama et al. (2009) also identified some of our reported N-arylsulfonylpyrazole series to be active inhibitors of the NS2B-NS3 virus. These promising results led our research group to investigate new approaches to other derivatives of N-sulfonylpyrazoles, thereby seeking alternative scaffolds for use as promising chemotherapeutics Elgemeie & Jones, 2002;Zhang et al., 2020). Accordingly, we synthesized the N-1-substituted derivative of N-sulfonylpyrazole 1.
The reaction 1 with ethyl bromoacetate 2 in the presence of anhydrous potassium carbonate in dry N,N-dimethylformamide at room temperature produced an adduct for which two possible isomers, the O-alkylated or N-alkylated N-sulfonylpyrazole structures 3 or 4, were considered. The 1 H NMR spectra of the product revealed the presence of an ISSN 2056-9890 amino group at 7.34 ppm and a pyrazole CH at 4.34 ppm, but spectroscopic data cannot differentiate between structures 3 and 4. The crystal structure determination indicated unambiguously the formation of the N-alkylated N-sulfonylpyrazole 4 as the only product in the solid state.

Structural commentary
The structure analysis confirms the formation of compound 4 (Fig. 1). The molecule displays an intramolecular hydrogen bond of the form N-HÁ Á ÁO S, and the intramolecular contact H12AÁ Á ÁO2 is also quite short at 2.38 Å (Table 1). Accordingly, the two rings face each other in a roughly 'Vshaped' form around the central SO 2 unit, with an interplanar angle of 53.45 (5) and torsion angles C7-C6Á Á ÁN1-N2 = À13.10 (10) and C11-C6Á Á ÁN1-C5 = 21.26 (11) . The corresponding angle N1-S1-C6 is the narrowest at S1 (the largest is, as expected, O1 S O2). In the pyrazole ring, the bond C4-C5 is the shortest, consistent with a major contribution from the resonance form shown in the Scheme. The exocyclic C5-N3 bond is appreciably shorter than the two C-N bonds in the ring. The side-chain atom sequence C12-C13-O5-C14-C15 displays an extended conformation. See Table 2 for selected molecular dimensions.

Supramolecular features
Two classical hydrogen bonds (Table 1) are observed, one from each hydrogen atom of the amino group; the contact H01Á Á ÁO1 i , involving the same hydrogen atom that forms the intramolecular hydrogen bond, is however much longer than H02Á Á ÁO3 ii . The molecules are thereby connected to form layers parallel to the bc plane (Fig. 2).

Figure 2
Packing diagram of 4 projected parallel to the bc plane. Dashed lines indicate intermolecular hydrogen bonds (intramolecular H bonds are omitted). Hydrogen atoms not involved in this hydrogen bonding system are omitted.

Figure 1
Structure of the title compound 4 in the crystal. Ellipsoids represent 50% probability levels. The dashed line indicates the intramolecular hydrogen bond.
so that one fewer hydrogen-bond donor is available and the packing is different from those of the previous structures.

Synthesis and crystallization
A mixture of compound 1 (0.01 mol), ethyl bromoacetate 2 (0.01 mol) and anhydrous potassium carbonate (0.01 mol) in N,N-dimethylformamide (5 mL) was stirred at room temperature for 2 h. The mixture was poured onto ice-water; the solid thus formed was filtered off and recrystallized from ethanol to give pale yellow crystals in 60% yield, m.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The NH hydrogen atoms were refined freely. The methyl group was refined as an idealized rigid group allowed to rotate but not tip ('AFIX 137 0 ; C-H 0.98 Å , H-C-H 109.5 ). Other hydrogen atoms were included using a riding model starting from calculated positions (C-H aromatic = 0.95, C-H methylene = 0.99 Å ). The U(H) values were fixed at 1.5 (for the methyl H) or 1.2 times the equivalent U iso value of the parent carbon atoms.  CrysAlis PRO (Rigaku OD, 2015); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: SHELXL2017 (Sheldrick, 2015).

Ethyl 2-(5-amino-1-benzenesulfonyl-3-oxo-2,3-dihydro-1H-pyrazol-2-yl)acetate
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. The NH hydrogens were refined freely. The methyl was refined as an idealized rigid group allowed to rotate but not tip. Other hydrogens were included using a riding model starting from calculated positions.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq S1 0.21827 (