Methyl 3-[(1-benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)formamido]propanoate: crystal structure, Hirshfeld surface analysis and computational chemistry

The title compound is constructed about a tri-substituted 1,2,3-triazole ring, with the substituent at the C atom flanked by the C and N atoms being a substituted amide group, and with the adjacent C and N atoms bearing phenyl and benzyl groups, respectively. In the crystal, pairwise amide-N—H⋯O(carbonyl) hydrogen bonds give rise to a centrosymmetric dimer.


Chemical context
The title 1,2,3-triazole-5-carboxamide derivative, (I), was recently prepared and characterized from a palladium-catalysed aminocarbonylation reaction with the use of dimethyl carbonate as a sustainable solvent (de Albuquerque et al., 2019). The motivation for preparing such molecules rests with the known pharmacological activity of these and related 1,2,3triazole derivatives (Bonandi et al., 2017). Unambiguous structure determination of (I) is reported herein, via X-ray crystallography, as is a detailed analysis of the supramolecular association by Hirshfeld surface analysis and computational chemistry.

Supramolecular features
The molecular packing in (I) features several identifiable points of contact, Table 1. The most evident of these are amide-N4-HÁ Á ÁO2(carbonyl) hydrogen bonds occurring between centrosymmetrically related molecules to give the dimer shown in Fig. 2(a). The molecules in the dimer are linked via a 12-membered {Á Á ÁOC 3 NH} 2 synthon and additional stability to the assembly is provided by methylene-C17-HÁ Á Á(benzene) interactions. The dimeric aggregates are connected into a supramolecular layer propagating in the ab plane via methylene-C3-HÁ Á ÁN2(azo) and benzene-C15-HÁ Á ÁO1(amide) interactions, Fig. 2(b). The layers stack in an . . . ABAB . . . pattern along the c axis and inter-digitate to potentially forminteractions. However, these are not apparent, Fig. 2(c). A more detailed analysis of the interactions occurring in the inter-layer region is provided by an analysis of the calculated Hirshfeld surfaces.  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.

Hirshfeld surface analysis
In order to probe the interaction between molecules of (I) in the crystal, Hirshfeld surfaces mapped with the normalized contact distance d norm (McKinnon et al., 2004), electrostatic potential (Spackman et al., 2008) and two-dimensional fingerprint plots were calculated using Crystal Explorer 17 (Turner et al., 2017) by established procedures (Tan et al., 2019). The electrostatic potentials were calculated using the wavefunction at the HF/STO-3 G level of theory. The brightred spots on the Hirshfeld surface mapped over d norm in Fig. 3(a), i.e. near the amide-H4N and carbonyl-O2 atoms, correspond to the amide-N-H4NÁ Á ÁO2(carbonyl) hydrogen bond (Table 1). This hydrogen bond is also reflected in Hirshfeld surface mapped over the electrostatic potential Fig. 3(b), where the blue (positive electrostatic potential) and red (negative electrostatic potential) regions are apparent around the amide-H4N and carbonyl-O2 atoms, respectively.
The methylene-C3-HÁ Á ÁN2(azo) and benzene-C15-H15Á Á ÁO1(amide) interactions are observed as faint-red spots on the d norm -mapped Hirshfeld surface in Fig. 4(a), with a distance of $0.3 Å shorter than the sum of their van der Waals radii,    Views of the Hirshfeld surface mapped over d norm for (I) in the range À0.249 to +1.397 arbitrary units, highlighting (a) weak C-HÁ Á ÁN and C-HÁ Á ÁO interactions and (b) short HÁ Á ÁC contacts, highlighted within red circles. Table 2 Summary of short interatomic contacts (Å ) in (I) a .

Contact
Distance Symmetry operation Notes: (a) The interatomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X-H bond lengths are adjusted to their neutron values. (b) These interactions correspond to those reported in Table 1.

Figure 5
A view of the Hirshfeld surface for (I) mapped with the shape-index property, highlighting the intermolecular C-HÁ Á Á interaction. Fig. 4(b) correspond to the inter-layer H7Á Á ÁC5, H17AÁ Á ÁC12 and H12Á Á ÁC15 short contacts listed in Table 2. Even though the C-HÁ Á Á interaction, Table 1, was not manifested on the d norm -mapped Hirshfeld surface, this interaction shows up as a distinctive orange 'pothole' on the shape-index-mapped Hirshfeld surface, Fig. 5. The overall two-dimensional fingerprint plot for the Hirshfeld surface of (I) is shown with characteristic pseudosymmetric wings in the upper left and lower right sides of the d e and d i diagonal axes, respectively, in Fig. 6(a). The delin-eated HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁN/NÁ Á ÁH contacts from the overall two-dimensional fingerprint plot are illustrated in Fig. 6(b)-(e), respectively. The percentage contributions from different interatomic contacts to the Hirshfeld surface of (I) are summarized in Table 3. The greatest contribution to the overall Hirshfeld surface are due to HÁ Á ÁH contacts, which contribute 46.7%. However, the HÁ Á ÁH contacts appear as a square-like distribution with a small beak at d e = d i $2.6 Å in Fig. 6(b), corresponding to H8Á Á ÁH11 '2.67 Å (symmetry operation: Àx, Ày, Àz + 1) indicating that all HÁ Á ÁH contacts have long-range characteristics. The HÁ Á ÁC/CÁ Á ÁH contacts on the Hirshfeld surface, which contribute 24.9% to the overall surface, Fig. 6(c), reflect the C-HÁ Á Á interaction and CÁ Á ÁH short contacts as discussed above. Consistent with the C-HÁ Á ÁO and C-HÁ Á ÁN interactions occurring in the crystal, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁN/NÁ Á ÁH contacts contribute 14.4 and 12.6%, respectively, to the overall Hirshfeld surface. These appear as two sharp symmetric spikes in the fingerprint plots at d e + d i ' 1.9 and 2.4 Å in Fig. 6(d) and (e), respectively. The contribution from the other interatomic contacts summarized in Table 2 has a negligible influence on the calculated Hirshfeld surface of (I).

Energy frameworks
The pairwise interaction energies between the molecules in the crystal of (I) were calculated using the 6-31G(d,p) basis set at the B3LYP level of theory. The total energy comprises four terms, i.e. the electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) energy terms and were calculated with Crystal Explorer 17 (Turner et al., 2017). The benchmarked energies were scaled according to Mackenzie et al. (2017) while E ele , E pol , E dis , and E rep were scaled as 1.057, 0.740, 0.871 and 0.618, respectively (Edwards et al., 2017). The energies for the identified intermolecular interactions are tabulated in Table 4 Table 4 Summary of interaction energies (kJ mol À1 ) calculated for (I).
from E ele and E dis , arises from the conventional amide-N-H4NÁ Á ÁO2(carbonyl) hydrogen bond. The next most significant energies of stabilization arise from the methylene-C3-HÁ Á ÁN2(azo) (dominated by E dis ) and benzene-C15-H15Á Á ÁO1(amide) (approximately equal contributions from E ele and E dis ) interactions. In terms of energy, the next most significant contributions comes from an interaction in the inter-layer region, namely the H17AÁ Á ÁC12 contact, Table 4. As for the other identified inter-layer contacts, E dis is the dominant contributor. Views of the energy framework diagrams down a axis are shown in Fig. 7 and confirm the crystal to be mainly stabilized by electrostatic and dispersive forces with a clear dominance from the latter. The total E ele of all pairwise interactions sum to À142.9 kJ mol À1 , while the total E dis computes to À251.1 kJ mol À1 .

Database survey
There is a sole literature precedent for (I), namely the analogue with ethyl carboxylate and N-phenylamide substituents at the C1-and C2-atoms, respectively (WAGROM; Katritzky et al., 2003), hereafter (II). An overlay diagram of (I) and (II) is given in Fig. 8. As anticipated, the five-membered rings and the -atoms of the three substituents exhibit close concordance but, beyond this, the molecular conformations of the terminal residues differ significantly.

Synthesis and crystallization
Compound (I) was prepared as described in the literature (de Albuquerque et al., 2019). The crystals were obtained by the slow evaporation from an ethanol solution of (I).

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 5. 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 1.2-1.5U eq (C). The nitrogen-bound H atom was located in a difference Fourier map and refined with N-H = 0.86AE0.01 Å , and with U iso (H) set to 1.2U eq (N).

Figure 8
Overlay diagram for (I), red image, and (II), blue image. The molecules have been overlapped so the five-membered rings are superimposed.

Figure 7
Perspective views of the energy frameworks calculated for (I) showing (a) electrostatic potential force, (b) dispersion force and (c) total energy, each plotted down the a axis. The radii of the cylinders are proportional to the relative magnitudes of the corresponding energies and were adjusted to the same scale factor of 50 with a cut-off value of 5 kJ mol À1 within 1 Â 1 Â 1 unit cells.  (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006), MarvinSketch (ChemAxon, 2010) and publCIF (Westrip, 2010).

Methyl 3-[(1-benzyl-4-phenyl-1H-1,2,3-triazol-5-yl)formamido]propanoate
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.