Crystal structure of 2-{[5-amino-1-(phenylsulfonyl)-1H-pyrazol-3-yl]oxy}-1-(4-methylphenyl)ethan-1-one

In this O-alkylated sulfonylpyrazolone, the sulfur atom lies 0.558 (1) Å out of the pyrazole ring plane. The NH2 group is involved in an intramolecular hydrogen bond to a sulfonyl oxygen atom and in a three-centre system with the two oxygen atoms of the side chain at C3, forming a ribbon structure.


Chemical context
We are interested in devising synthetic strategies for heterocyclic ring systems containing the N-sulfonyl-and N-sulfonylamino moiety, which have shown significant biological activity as novel antiviral and antimicrobial agents (Azzam et al., 2017(Azzam et al., , 2020Elgemeie et al., 2017Elgemeie et al., , 2019Zhu et al., 2013). In addition, some of our recently published N-arylsulfonylpyrazoles (Elgemeie & Hanfy, 1999;Elgemeie et al., 1998Elgemeie et al., , 2002Elgemeie et al., , 2013 have been shown to be active as inhibitors of cathepsin B16 enzyme and NS2B-NS3 virus (Sidique et al., 2009;Myers et al., 2007). Based on these promising results, and in a continuation of our recent research to develop innovative and simple syntheses of other novel derivatives of N-sulfonylpyrazoles, we have begun to seek different scaffolds for use as potential pharmaceuticals (Zhang et al., 2020). In particular, we have now synthesized an O-alkyl derivative of N-sulfonylaminopyrazole 1.
Thus, the reaction of 5-amino-1-(phenylsulfonyl)-1,2-dihydro-3H-pyrazol-3-one 1 with 2-bromo-1-(p-tolyl)ethan-1- Reaction scheme for the preparation of the title compound 4. one 2 in N,N-dimethylformamide in the presence of potassium carbonate at room temperature furnished an adduct for which two possible isomers, the O-alkylated or N-alkylated Nsulfonylpyrazole structures (3 or 4) were considered. The 1 H NMR spectrum of the product showed four singlet signals at = 2.40, 4.91, 5.45 and 6.34 ppm assigned for CH 3 , CH-pyrazole, CH 2 and NH 2 protons, in addition to signals assigned to aromatic protons. The available spectroscopic data cannot differentiate between structures 3 and 4 ( Fig. 1). Thus, the X-ray structure of this product was determined, indicating unambiguously the formation of the O-alkylated N-sulfonylpyrazole 4 as the sole product in the solid state.

Structural commentary
The molecular structure of 4 is shown in Fig. 2. Selected molecular dimensions are given in Table 1. An intramolecular hydrogen bond N3-H02Á Á ÁO3 is observed. The pyrazole ring is planar (r.m.s. deviation 0.015 Å ) and its dimensions may be regarded as normal. The sulfur atom lies 0.558 (1) Å outside the ring plane, and the nitrogen atom N1 is thus significantly pyramidalized; it lies 0.216 (1) Å out of the plane of the three atoms to which it binds. The atom sequence C4-C3-O1-C6-C7-C21-C22 presents an extended conformation, with all torsion angles close to AE180 . The planes of the pyrazole and the tolyl rings are thus almost parallel [interplanar angle 14.46 (2) ].

Supramolecular features
The classical hydrogen bond N3-H01Á Á ÁO2 (Àx, y + 1 2 , Àz + 1 2 ) links the molecules to form a broad ribbon structure parallel to the b axis. H01 also has a short but non-linear contact to O1 (same operator), representing the weaker component of an asymmetric three-centre system (Fig. 3). The vector between translationally adjacent, coplanar ribbons is [401], so that the layer of ribbons is parallel to (104). The second amine hydrogen atom H02 is only involved in the intramolecular hydrogen bond (see above). The layers are linked by interactions C14-H14Á Á ÁO2 (x, Ày + 1 2 , z + 1 2 ), which connect every second layer, penetrating the layer in between. See Table 2

Figure 2
The molecular structure of compound 4. Ellipsoids represent 50% probability levels. The dashed line indicates an intramolecular hydrogen bond.

Database survey
Version 5.41 of the Cambridge Structural Database (Groom et al., 2016) was used for a CSD search with CONQUEST (Bruno et al., 2002). The relative frequency of O-vs N2-alkylation of such pyrazole ring systems was investigated by a search for pyrazoles with a C O function at C3, H at C4, substituted at N2, no fused rings [as in our recent publication (Metwally et al., 2021);23 hits] or with substitution at the oxygen atom, H at C4, no substituent at N2, no fused rings (as here; 36 hits). Only one hit was registered for a pyrazole similar to 4 bearing a substitute at the C3-O group together with an N-substituent at C5 and an S-substituent at N1, namely 1-(4-fluorobenzenesulfonyl)-5-amino-1H-pyrazol-3-yl thiophene 2-carboxylate, refcode YILPUF (Myers et al., 2007).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The hydrogen atoms of the NH 2 group were refined freely. The methyl group was refined as an idealized rigid group allowed to rotate but not tip, with C-H = 0.98 Å and H-C-H = 109.5 . Other hydrogens 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 or 1.2 times the equivalent U iso value of the parent carbon atoms for methyl and non-methyl hydrogens, respectively. Six reflections were omitted because their calculated and measured F o 2 and F c 2 values differed by more than 7 s.u. The occurrence of such apparent outliers seems to be a general consequence of collecting data to high 2 values (here 76 ), whereby spherical atom scattering factors become less applicable. Special refinements using aspherical atom scattering factors can lead to greatly improved R values and thus fewer outliers, but this method is not yet widely employed. However, even for 'normal' refinement, it is still considered best practice to collect data to high diffraction angles wherever possible (Sanjuan-Szklarz et al., 2016).

2-{[5-Amino-1-(phenylsulfonyl)-1H-pyrazol-3-yl]oxy}-1-(4-methylphenyl)ethan-1-one
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. Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)