(4-Nitrophenyl)methyl 2,3-dihydro-1H-pyrrole-1-carboxylate: crystal structure and Hirshfeld analysis

The title compound has a ‘banana’ shape, with the dihedral angle formed by the outer rings being 8.30 (7)°. In the crystal, the three-dimensional architecture features nitrobenzene-C—H⋯O(carbonyl), pyrrole-C—H⋯O(nitro), π(pyrrole)—π(nitrobenzene) and nitro-O⋯π(pyrrole) interactions.


Chemical context
Many hydroxylated prolines and homoprolines have the ability to inhibit glycosides and glycosyltransferases, key enzymes in biosynthesis and the processing of glycoproteins and glycolipids (Rule et al., 1985;Fleet & Son, 1988;Wong, 1997). Glycoproteins are macromolecules involved in the recognition (cell-cell interactions and host-pathogen) and control of mechanisms associated with biological structures. Thus, compounds that are capable of inhibiting the biosynthetic pathway of glycoproteins have broad chemotherapeutic potential in the treatment of metabolic diseases such as diabetes, obesity, cancer, tuberculosis and viral infections among others (Kordik & Reitz, 1999;Nishimura, 2003;Cheng & Josse, 2004). Some hydroxylated prolines are of interest in this context owing to their ability to inhibit glycosidases and because they are found as substructures of natural bioactive compounds. For example, (2S,3R,4S)-3,4-dihydroxyproline (II), see scheme, is found as a component of the repeating decapeptide sequence of the Mefp1 adhesive protein (Mytilus edulis foot protein 1), produced by the marine mussel, Mytilus edulis (Taylor et al., 1994;Taylor & Weir, 2000). This protein is responsible for the fixation of mussels to rocks. As a part of a study into the development of new and flexible methodologies for the efficient synthesis of several natural and synthetic products with important pharmacological properties, using the Heck-Matsuda arylation reaction as a crucial step, (II) was prepared from the title compound, (I), for the purpose of evaluating the best protecting group for use in future syntheses of greater complexity (Garcia, 2008). During the Heck-Matsuda reaction, it was found that the protective group of the nitrogen atom in (I) exerted some influence on the reaction time, but did not influence the yield of the expected intermediate when compared to the Heck-Matsuda reaction applied to the enecarbamate, ethyl 2,3-dihydro-1H-pyrrole-1carboxylate (Garcia, 2008). It is noted that the first synthesis of (I) was actually reported nearly 50 years ago (Heine & Mente, 1971). Herein, the crystal and molecular structures of (I) are described along with an analysis of the calculated Hirshfeld surfaces.

Structural commentary
The molecular structure of (I), Fig. 1, is a 1-methylene-4nitrobenzene ester derived from dihydropyrrole-1-carboxylic acid. In (I), the dihydropyrrole ring is almost planar with the r.m.s. deviation of the five fitted atoms being 0.0049 Å , and the maximum deviation of any of the constituent atoms being 0.0065 (11) Å for atom C2. The adjacent C 2 O 2 residue (O1,O2,C5,C6) is essentially co-planar, with the dihedral angle between the two planes being 4.56 (9) . The planarity extends to the 4-nitrobenzene ring, with the dihedral angle between the C 2 O 2 and C 6 planes being 4.58 (8) . However, the molecule is not planar but rather is curved as the outer rings lie to the same side of the central C 2 O 2 residue; the dihedral angle = 8.30 (7) . To a first approximation, the nitro group is co-planar  Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of (I), showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. with the benzene ring to which is connected, as seen in the value of the O4-N2-C10-C9 torsion angle of 173.50 (15) .

Hirshfeld surface analysis
The Hirshfeld surface calculations for (I) were performed as per a recent study (Zukerman-Schpector et al., 2017) and serve to provide additional information on the molecular packing.
In addition to the bright-red spots on the Hirshfeld surface mapped over d norm in Fig. 3 near the pyrrole-H4, nitrobenzene-H12, and the nitro-O3 and carbonyl-O1 atoms, Two views of the Hirshfeld surface for (I) mapped over d norm in the range À0.225 to +1.393 au, showing intermolecular C-HÁ Á ÁO contacts as black dashed lines.

Figure 4
Views of Hirshfeld surfaces for (I) mapped: (a) over d norm in the range À0.225 to + 1.393 au, highlighting inter-and intra-layer CÁ Á ÁC and CÁ Á ÁH/ HÁ Á ÁC contacts as black and sky-blue dashed lines, respectively, and (b) over the electrostatic potential in the range AE0.077 au (the red and blue regions represent negative and positive electrostatic potentials, respectively), showing intermolecular N-OÁ Á Á andcontacts as black dotted lines.
The overall two-dimensional fingerprint plot and those delineated into HÁ Á ÁH, OÁ Á ÁH/HÁ Á ÁO and CÁ Á ÁH/HÁ Á ÁC contacts (McKinnon et al., 2007) are illustrated in Fig. 5a-d, respectively, and the percentage contribution from the identified interatomic contacts to the Hirshfeld surface are summarized in Table 3. The comparatively low, i.e. 39.0%, contribution from HÁ Á ÁH contacts to the overall surface is due to the involvement of many hydrogen atoms in directional intermolecular interactions, e.g. C-HÁ Á ÁO, (Tables 1 and 2). Hence, the interatomic HÁ Á ÁH contacts have a reduced influence in the crystal as their interatomic separations are equal to or greater than sum of their van der Waals radii (Fig. 5b). Conversely, the relatively significant contribution of 33.8% from OÁ Á ÁH/HÁ Á ÁO contacts to the Hirshfeld surface is consistent with this observation. The fingerprint plot delineated into OÁ Á ÁH/HÁ Á ÁO contacts (Fig. 5c) features a pair of green aligned points within the pair of spikes with their tips at d e + d i $2.3 Å superimposed upon a distribution blue points characterizing intermolecular C-HÁ Á ÁO interactions. The short interatomic CÁ Á ÁH/HÁ Á ÁC contacts in the inter-and intra-layer regions are represented by the two pairs of short forcepslike spikes at d e + d i $2.8 and 2.9 Å , respectively, in Fig. 5d. The small but discernible contributions from interatomic CÁ Á ÁC and CÁ Á ÁN/NÁ Á ÁC contacts (Table 3) result from short inter-layer contacts andstacking interactions. The presence of the N-OÁ Á Á contact in the structure is also evident from the contribution of CÁ Á ÁO/OÁ Á ÁC and NÁ Á ÁO/ OÁ Á ÁN contacts to the Hirshfeld surface as summarized in Table 3. The small contributions from the other remaining interatomic contacts (Table 3) have a negligible influence on the packing.

Database survey
Dihydropyrrole rings as found in (I) have rarely been characterized crystallographically and only one structure is deposited in the Cambridge Structural Database (Groom et al., 2016), namely the adduct, ZnI 2 (4,5-dihydro-3H-pyrrole) 2 (refcode WAZXAW; Freer et al., 1993). Here, despite having sp 2 -carbon centres as in (I), the rings are planar with one lying on a crystallographic mirror plane and the other disposed across a mirror plane (r.m.s. deviation = 0.007 Å ), implying disorder in the latter.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 4. The carbon-bound H atoms were placed in calculated positions (C-H = 0.93-0.97 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2U eq (C).

(4-Nitrophenyl)methyl 2,3-dihydro-1H-pyrrole-1-carboxylate
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.