η3-allyl-Pd(II) complexes of 2-, 3- and 4-pyridylmethyl-coumarin esters

A series of 2-, 3- and 4-pyridylmethyl-coumarin esters ligands (1–3) and their η3-allyl palladium complexes (1-Pd–3-Pd) have been designed, synthetized, and characterized. NMR analysis of compounds 1-Pd–3-Pd indicated the presence of the allyl fragment. The molecular structures of 2, 3 and 1-Pd were determined by X-ray crystallographic analysis. The molecular structure of 1-Pd reveals that coumarin ligand (2) is coordinated to the palladium center via a monodentate fashion through the nitrogen atom of the pyridinyl fragment while, the allyl group is binding via a η3 fashion in an overall square-planar geometry completed with a chloride atom. The crystal packing is stabilized by a variety of weak intermolecular conventional and non-conventional interactions involving C–H–O/N hydrogen bonds, π–π and C–H–π interactions, which have been analyzed by Hirshfeld surface and non-covalent interactions analysis. The intermolecular interaction energies were explored using an energy framework analysis, which revealed that π–π and C–H–π interactions serve as the primary building blocks in these crystal packing.

According to the aforementioned and continuing with the modification of commercial natural products via the introduction of pyridinyl-moieties [47][48][49][50], herein we described the design, synthesis and characterization of the 2-, 3-and 4-pyridylmethyl-coumarin esters (1)(2)(3) and their corresponding allyl-palladium(II) complexes (1-Pd-3-Pd), in those compounds the mono-substituted pyridine ligands which acts as Lewis base is attacked by Lewis acid Pd(II) cation as electrophile. In this regard, the aim is studied the effect of the position of the nitrogen atom of the pyridylmethyl-coumarin esters towards Pd(II) metal which can generate significative changes in their molecular and crystal structure. The crystal structure of the ligands 2 and 3 and allyl-palladium(II) complex (1-Pd) was determined by X-ray analysis. A detailed analysis of weak intermolecular interactions present in the crystal packing using energy framework (intermolecular interaction topologies) and non-covalent interactions (NCI) topological analysis was performed.
Column chromatography was carried out on silica gel 60 (Aldrich, 230-400 mesh ASTM). Melting points were recorded on a Mel-Temp II apparatus and were reported without correction. Infrared spectra were recorded on an FTIR 200 PerkinElmer spectrophotometer in the 4000-400 cm 1 range using KBr pellets. NMR spectra were obtained on a Bruker Ascend 400 spectrometer at 400.13 MHz for 1 H and 100.62 MHz for 13 C{ 1 H}, and two-dimensional heteronuclear and homonuclear experiments (COSY, HSQC, and HMBC) were performed. Chemical shifts (ppm) of 1 H and 13 C{ 1 H} spectra are relative to the frequency of SiMe 4 .

Single crystal X-ray crystallography
Single crystals of 2, 3 and 1-Pd were grown by slow evaporation at room temperature of a CHCl 3 solution. Intensity data were collected at 295 K on a Gemini CCD diffractometer with either graphite-monochromated Mo-Kα (λ = 0.71073 Å) radiation. Data were integrated, scaled, sorted, and averaged using the CrysAlis software package [51]. The initial structures were solved with the SHELXT structure solution program [52] using Intrinsic Phasing and refined with the SHELXL [53] and refinement package by using least-squares minimization against F2; both programs running in the Olex2 suite [54]. In 2, the pyridine fragment is disordered over two sets of sites [occupancy ratio 0.51(2):0.49 (2)]. In 1-Pd, the allyl group is disordered over two sets of sites [occupancy ratio 0.784(10):0.216 (10)]. Crystallographic details and structure refinements are presented in Table 1.

Computational details
The Hirshfeld surfaces, fingerprint plots and energy frameworks were calculated using the Crystal Explorer (version 17.5) software [55,56].
The total interaction energy was calculated by generating the molecular cluster ( Figure S34-S37) of radius 3.8 Å around the selected molecule. The interaction energy framework calculations were carried out by employing symmetry operations to generate molecular wave functions and to compute the electron densities of the cluster of all molecules present around the selected molecule using the B3LYP/DGDZVP energy model with the scale factors to determine E tot : k ele = 1.057, k pol = 0.740, k dis = 0.871, k rep = 0.618, which were computed using TONTO [57,58]. Energy Framework representations of the intermolecular interactions in the structure of all compounds are presented in Figure S38. The electrostatic, dispersion, and total interaction energies between molecular pairs are colored red, green, and blue, respectively, with the thickness of each cylinder connecting molecules proportional to the magnitude of the energy (tube size 150 and cutoff energy 8 kJ/mol).
The calculations of the non-covalent interactions were performed with the Gaussian 09 software [59]. The B3LYP/DGDZVP level of theory wave function was used to generate the NCI. Visualization of isosurfaces was plotted with the VMD program [60].

General procedure for the preparation of 2-, 3and 4-pyridylmethyl-coumarin esters (1-3)
A solution of 2-, 3-or 4-(bromomethyl)pyridine hydrobromide (1.55 mmol) in H 2 O (5 mL) was added to a solution of 4-hydroxycoumarin (1.55 mmol) and anhydrous K 2 CO 3 (6.20 mmol) in tetrahydrofuran (25 mL). The purple suspension obtained was refluxed for 24 h. After cooling, the resulting suspension was filtered, and the solvent was removed under reduced pressure to give a deep brown oil. The deep brown oil was then dissolved in dichloromethane (3 × 25 mL), dried over Na 2 SO 4 , then filtered through a bed of Celite, and evaporated to dryness to give a deep brown solid. The deep brown solid was purified by column chromatography on silica gel using using n-hexanes/ ethyl acetate (7:3) as eluents to afford compounds 1-3 as colorless powder or crystals. The report yields of the compounds 1-3 was achieved after of the purification by column chromatography (CC

General procedure for the preparation of allyl-palladium(II) complexes (1-Pd-3-Pd)
A mixture of the corresponding ligand 1-3 (0.42 mmol) and allyl-palladium(II) chloride dimer (0.21 mmol) in thf (50 mL) was refluxed for 24 h. After cooling, the resulting solution was filtered through a bed of Celite, and the solvent was removed by slow evaporation to afford compound 1-Pd as yellow crystals and compounds 2-Pd and 3-Pd as white powder.  13

NMR studies of ligands and (1-3) and their η 3 -allyl-palladium(II) complexes (1-Pd-3-Pd)
In the 1 H NMR spectra of ligands 1-3 a series of signals that indicated the presence of the ortho-substituted benzene ring as a ABCD pattern as well as the signals of the ortho-, meta-or para-substituted methylpyridine group were observed. In this context, at a higher frequency, a signal that is attributed to the proton ortho to nitrogen atom of the pyridine group (δ = 8.71-8.65 ppm in compound 1-3, additionally in compound 2 a signal at δ = 8.78 ppm that is attributed to the proton ortho to nitrogen atom of the pyridine group near to the methylene group which is binding to oxygen atom). Signals at low frequencies correspond to hydrogen atom of the pyrone group (δ = 5.83-5.75) and the methylene group that is linking to oxygen atom (δ = 5.36-5.25 ppm), respectively.
In the 1 H NMR spectra of (1-Pd-3-Pd), the signal attribute to ortho proton of pyridine group is shifted to higher frequencies by ca. 0.10-0.25 ppm with respect to the free ligands, which confirmed the coordination of the pyridine arm toward palladium atom. In particular, the signals attributed to hydrogen atom of the pyrone group in The 13 C{ 1 H} NMR spectra of ligands 1-3 showed the signals of the coumarin fragment and the o-, m-or p-pyridine group to high frequencies (δ = 91.7-91.3 ppm) and two signals to low frequencies that correspond to the carbon atom binding to hydrogen atom of pyrone group (δ = 91.7-91.3 ppm) and the carbon of methylene group that is linking to oxygen atom (δ = 71.6-68.7 ppm).
In the 13 C{ 1 H} spectra of (1-Pd-3-Pd), the signal attributed to ortho carbon of pyridine group is shifted to higher frequencies by ca. 1.4-2.5 ppm, respect to the free ligands, which confirmed the coordination of the pyridine arm toward Palladium atom. In particular, the signals attributed to carbon atom binding to hydrogen atom of the pyrone group and the carbon from methylene group bonded to pyridine group in compounds 1-Pd-3-Pd do not display a significant change from chemical shift with respect to the free ligands. The signals attributed for the allyl carbons were not observed in all complexes, in particular the spectrum of compound 1-Pd two broad signals are displayed at 112.9 and 62.1 ppm for CH and CH 2 carbons. In 2-Pd, one signal is observed at δ = 114.3 ppm, while in 3-Pd no signals were found. A similar phenomenon has been observed in another η 3 -allyl palladium complexes previously reported [65,66].

Molecular structures of 2 and 3 and 1-Pd
The molecular structure compounds 2, 3 and 1-Pd are depicted in Fig. 1. Selected bond lengths, angles and torsion angles are given in Tables S1-S3. The molecular structure of compounds 2 and 3 revealed that the coumarin moiety and methyl-pyridine group are nearly perpendicular while in complex 1-Pd those groups are nearly coplanar which are forming a dihedral angle between the two rings 50.74° in 2, 49.38° in 3 and 17.46 in 1-Pd, respectively. The molecular structure of 1-Pd reveals that the palladium center is η 3 -ligated by the allyl fragment, the nitrogen atom of pyridine group and the chlorine atom which are orientated syn to the metal center which is adopting a square-planar geometry. The Pd1-N1

Crystal structures of 2, 3 and 1-Pd
The existence of weak intermolecular C-H-O/N hydrogen bonds and π-π, C-H-π a interactions in the crystal packing of compounds 2, 3 and 1-Pd, was analyzed according to the next numeral criteria d(H-A) [2.0-3.0 Å and ∡ [90-180°] [67], and for the plane separation for face-to-face and offset face-to-face [3.0 and 3.8 Å] with a centroid-to-centroid distance up to 5 Å for edge-to-face interactions and lone pair-π interaction can be considered as significant if the distance separating the electron-rich atom from one atom of the sixmembered ring is in the range of the sum of their van der Waals radii [68,69], respectively.
The crystal packing of 2 and 3 exhibits a supramolecular assembly via two weak C-H-O hydrogen bond in a zig-zag pattern, generating two eight membered rings with a graph-set description of R . The distance found between adjacent layers is 3.596 Å and 3.457 in 2 and 3, respectively ( Fig. 2 and 3).
The molecular structure of compound 1-Pd displayed that the allyl fragment is disordered in two positions, where the central CH group of the allyl group is oriented in opposite directions, the central CH group with minor disorder is directed away from the main molecule (1-Pda) and in the other case is directed inward from the main molecule (1-Pdb), respectively.
In the supramolecular structure of 1-Pd two types of dimers can be distinguished which is promoted by parallel displaced π-π and C-H-π interactions mainly. Dimers display different arrays; for example, in the first case, chlorine atoms bonded to palladium atom are oriented toward the inside, while in the second case chlorine atoms are oriented toward the outside of the dimer formed. In both cases, the chlorine atoms are antiparallel to each other. In the first case, the dimers are stabilized by parallel displaced C-H-π and π-π forming an angle Cg py -Cg A = 3.997 Å and interplanar angle formed by pyridine and coumarin ring = 18.42°] (Fig. 4), respectively. These arrays do not suffer changes due to orientation from central CH group of the allyl group which is oriented in opposite direction. In 1-Pda, both dimers are interconnected through C-H-π interactions promoted by the central hydrogen atom of the allyl group with the pyridine ring, and two C-H-O hydrogen bonds between the oxygen atom of the carbonyl group and one hydrogen atom of the pyridine   (Fig. 5), respectively. The main difference between 1-Pda and 1-Pdb in the packing is the presence of H-Cl hydrogen bonding in 1-Pdb.
The Hirshfeld surfaces of 2, 3 and 1-Pd are illustrated in Fig. 6   interactions, where blue zones represent convex regions due to carbon atoms of π stacked molecule inside the surface, and the red zones represent concave regions due to pyridine, pyrone and benzene rings of the π stacked according with one of the next ways face-to-face, offset face-to-face or edgeto-face stacking. Curvedness surface indicates the location of π-π stacking interactions which are evident of both sides on the molecules and this surface appears as a flat green region for the coumarin and pyridine rings.
2D fingerprint plots for 2, 3 and 1-Pd are shown in Fig. 7, and the relative contribution of different interactions is presented in Figure  Contributions at 1-Pda and 1-Pdb do not show significant differences, suggesting that the disorder of the allyl group is not a crucial factor to be considered.
Energy Framework analysis of the 3D-topologies of compounds 2, 3, 1-Pda and 1-Pdb revealed that the lattice energy for free ligands 2 and 3 is found to be − 219.3 and − 238.63 kJ/mol, respectively, the difference of 20 kJ/ Fig. 6 Hirshfeld surfaces mapped with d nomr (left), shape index (middle) and curveness (right) of the compounds 2, 3 and 1-Pd mol can be attributed to the existence of hydrogen bonds H-N in 3, while that for 1-Pda and 1-Pdb is found to be − 300.1 and − 295.3 kJ/mol, respectively, which suggest that both packing are displaying similar arrays (Fig. 8,   S36-S42, and Table S6 and S7). In 2 and 3, columns are formed by π-π interactions stacking which serve as the pillars in these crystal structures (shown as the thickest tubes in Fig. 8). The pairwise interaction in 2 and 3 formed by In the energy framework of 1-Pda and 1-Pdb, four main interactions can be observed; two of them are displaying in a zig-zag pattern promoted by π-π interactions stacking via dimeric structures from the stacking of coumarin rings, and their values of interaction energies are similar for each molecule (E Total = − 61.7 and − 61.1 kJ/mol; − 72.0 kJ/ mol, in 1-Pda and 1-Pdb, respectively) which suggest that the dimers most favored are when the chloride atoms are oriented toward the inside of the dimer, while one of them is displaying a hydrogen bond (H-O that is forming a R 1 2 (10) ring with a total energy of − 44.0 and − 44.3 kJ/mol, in 1-Pda and 1-Pdb, respectively). Moreover, in 1-Pda, the interaction C-H allyl -π is having a total energy of − 42.7 kJ/ mol, while in 1-Pdb-35.5 kJ/mol, which could suggest that C-H allyl -π interactions are favored while in 1-Pdb could suggest that C-H allyl -π and H-Cl bond are having a synergic effect.
In order, to further characterize the different assemblies prompted by π-π and C-H-π interactions in molecules 2, 3, 1-Pda and 1-Pdb a NCI analysis was performed. The existence and weak attractive nature of the π-π and C-H-π interactions were confirmed by the presence of green isosurfaces located between the pairwise (Fig. 9). Moreover, the NCI plot of 1-Pda and 1-Pdb also reveals the existence of π-π stacking interactions since a more extended isosurface located between the pyridine ring also appears upon complexation. In addition, intramolecular molecular interactions present between one hydrogen atom of the aromatic and oxygen atom bonding to methylene group were observed in 2 and 3, and between one hydrogen atom of methylene group and chlorine atom was displayed in 1-Pda and 1-Pdb.

Conclusion
The coordination capacity of three 2-, 3-and 4-pyridylmethyl-coumarin esters (1-3) toward η 3 -allyl-chloridepalladium(II) dimer was performed, and complexes 1-Pd-3-Pd were generated. The molecular structure of 1-Pd shows that ligand 1 is coordinated to the palladium center via the nitrogen atom of the pyridine ring and the coordination sphere of the metal is completed by the allyl fragment which is displaying a typical η 3 -ligation and the chlorine atom which are orientated syn to the metal center. In the crystal structures of 2 and 3 intermolecular hydrogen bonds of type C-H-O were identified, which are generating (14) graph-set, while in the ligand 3 were also visualized C-H-N contacts which are forming a twenty-two membered ring [ R 2 2 (22)] in both ligands were formed dimer via π-π stacking and C-H-π interactions which are generating layers. The dimers generated in the crystal packing of 1-Pd by π-π and C-H-π interactions are having different arrays in the first case, chlorine atoms bonded to palladium atom are oriented toward the inside while in the second case chlorine atoms are oriented toward the outside of the dimer formed, in both cases the chlorine atoms are antiparallel to each other. The 3D Hirshfeld surface analysis revealed that H-H contacts comprise most interactions, and relative contributions for intermolecular H-O, H-N and H-C contacts to the Hirshfeld surface area are lightly different. Shape index and Curvedness were useful to visualize and analyze π-π stacking and C-H-π interactions in both sides of molecule inside the surface in compound 2, 3 and 1-Pd. The 3D molecular energy frameworks and NCI analysis proved that the dispersion energy dominates all other energies, and their visualization identifies the packing order of all molecules in the crystalline environment. and methodology; RS-P assisted in the validation, formal analysis and data curation; WF-S contributed to the methodology and supporting; DM-O was involved in the formal analysis and data curation; NA-L contributed to supporting and formal analysis; VS-P was involved in supporting and formal analysis; JC-B contributed to the validation, formal analysis and data curation. All authors reviewed the manuscript.