Rearrangement of Imidazolidine to Piperazine Rings in the Presence of Dy III †

: The formation of imidazolidines from secondary amines and aldehydes is well known. This small cycle can act as a nitrogen donor, and it is usually stable when it coordinates to metal ions. Sometimes, imidazolidines acting as ligands undergo breaking of the C-N bond when coordinating to the metal center, yielding related amines. However, the reorganization of the imidazolidine into a piperazine ring is quite an unusual process. In this work, we describe the transformation of a zinc complex with a ligand containing two imidazolidine moieties into a zinc complex with a piperazine fragment as donor, in the presence of a dysprosium salt.


Introduction
Nitrogen heterocycles are undoubtedly the most important structural motifs in medical chemistry and pharmaceuticals [1]. These include imidazolidines and piperazines [2], which are also potential ligands for the formation of metal complexes [3,4]. The stability of imidazolidine-based complexes greatly depends on the substituents attached to the nitrogen donors. Thus, there are many complexes with imidazolidine ligands that have been shown to be stable in solution, while others undergo hydrolysis very easily [5]. When this hydrolysis takes place, it typically cleaves the imidazolidine ring to transform the ligand into an amine [5]. However, in some cases, although very rare, the conversion of the imidazolidine ring into a piperazine heterocycle has also been described. To our knowledge, this transformation has only been described twice in the literature, and it took place in the presence of Cu II ions [6,7]. In this work, we describe the conversion of a ligand containing two imidazolidine rings into one with a piperazine cycle, a reaction that occurs in the presence of a dysprosium(III) salt.

Materials and General Methods
All chemical reagents and solvents were purchased from commercial sources, and used as received without further purification. 1 H NMR spectra of 1 and 2·1.75H 2 O were recorded on a Varian Inova 400 spectrometer, using DMSO-d 6 as solvent.
Single X-ray data for 2·1.75H 2 O were collected at 100 K on a Bruker D8 VENTURE PHOTON III-14 diffractometer, employing graphite-monochromated Mo-kα (λ = 0.71073 Å) radiation. Multi scan absorption corrections were applied using SADABS [8]. The structure was solved using standard direct methods, employing SHELXT [9], and then refined using the full matrix least-squares techniques on F 2 , using SHELXL [10] from the program package SHELX.

Synthesis and Spectroscopic Characterization
The trinuclear zinc complex 1 was obtained using a template method, by mixing pentaethylenehexamine and 5-bromo-2-hydroxy-3-methoxybenzaldehyde in the presence of zinc acetate, as summarized in Figure 1.

Synthesis and Spectroscopic Characterization
The trinuclear zinc complex 1 was obtained using a template method, by mixing pentaethylenehexamine and 5-bromo-2-hydroxy-3-methoxybenzaldehyde in the presence of zinc acetate, as summarized in Figure 1.   The addition of dysprosium(III) nitrate to an acetonitrile/methanol solution of 1 yields the dinuclear zinc complex 2·1.75H 2 O (Figure 1), which contains the new [L 2 ] 2− donor with a piperazine ring. This heterocycle seems to come from the initial imidazolidine rings present in the [L 1 ] 4− ligand in 1, through a hydrolysis and rearrangement process. This transformation, although uncommon, has been previously described for copper(II) complexes [6,7] but, as far as we know, it has never been reported in the presence of a lanthanoid ion. Both complexes were characterized using 1 H NMR spectroscopy. In addition, 2·1.75H 2 O has been unequivocally identified by single X-ray diffraction studies.
The 1 H NMR spectrum of 1 shows one singlet at 8.4 ppm (2H), assigned to the imine protons, and one singlet (2H) and one multiplet (6H) between 6.75 and 6.98 ppm, in agreement with the existence of four aromatic rings, which are not all equivalent. This confirms the tetracondensation of the amine and the aldehyde. Furthermore, the presence of two singlets at ca. 3.7 ppm points to the existence of two inequivalent imidazoline protons (H17 and H17' in Figure 1), in agreement with previous results [11], and this reinforces the tetracondensation. In addition, it should be noted that only one set of signals is present in the 1 H NMR spectrum of 1, in agreement with the existence of only one species in solution, and this spectrum does not show any evidence of hydrolysis.
In the case of 2·1.75H 2 O, the 1 H NMR spectrum in DMSO-d 6 ( Figure 2) clearly shows the existence of two equivalent imine moieties (singlet at 8.5 ppm), and just two equivalent aromatic rings (two singlets at 6.96 and 7.07 ppm), without any other peak in the aromatic region, indicating the high purity of this species. The addition of dysprosium(III) nitrate to an acetonitrile/methanol solution of 1 yields the dinuclear zinc complex 2·1.75H2O (Figure 1), which contains the new [L 2 ] 2-donor with a piperazine ring. This heterocycle seems to come from the initial imidazolidine rings present in the [L 1 ] 4-ligand in 1, through a hydrolysis and rearrangement process. This transformation, although uncommon, has been previously described for copper(II) complexes [6,7] but, as far as we know, it has never been reported in the presence of a lanthanoid ion. Both complexes were characterized using 1 H NMR spectroscopy. In addition, 2·1.75H2O has been unequivocally identified by single X-ray diffraction studies.
The 1 H NMR spectrum of 1 shows one singlet at 8.4 ppm (2H), assigned to the imine protons, and one singlet (2H) and one multiplet (6H) between 6.75 and 6.98 ppm, in agreement with the existence of four aromatic rings, which are not all equivalent. This confirms the tetracondensation of the amine and the aldehyde. Furthermore, the presence of two singlets at ca. 3.7 ppm points to the existence of two inequivalent imidazoline protons (H17 and H17' in Figure 1), in agreement with previous results [11], and this reinforces the tetracondensation. In addition, it should be noted that only one set of signals is present in the 1 H NMR spectrum of 1, in agreement with the existence of only one species in solution, and this spectrum does not show any evidence of hydrolysis.
In the case of 2·1.75H2O, the 1 H NMR spectrum in DMSO-d6 ( Figure 2) clearly shows the existence of two equivalent imine moieties (singlet at 8.5 ppm), and just two equivalent aromatic rings (two singlets at 6.96 and 7.07 ppm), without any other peak in the aromatic region, indicating the high purity of this species. Thus, the comparison of this spectrum with that of 1 shows the disappearance of four aromatic protons, according to the removal of two aromatic rings in 2·1.75H2O with respect to 1. Unfortunately, most of the aliphatic protons of 2·1.75H2O are hidden by the DMSO and water peaks, but, despite this, the 1 H NMR spectrum is in complete agreement with the formation of the new piperazine donor. Accordingly, the 1 H NMR studies suggest that both complexes are stable in solution, and, therefore, that the transformation of complex 1 into 2·1.75H2O is mediated by the presence of the dysprosium(III) nitrate. Thus, the comparison of this spectrum with that of 1 shows the disappearance of four aromatic protons, according to the removal of two aromatic rings in 2·1.75H 2 O with respect to 1. Unfortunately, most of the aliphatic protons of 2·1.75H 2 O are hidden by the DMSO and water peaks, but, despite this, the 1 H NMR spectrum is in complete agreement with the formation of the new piperazine donor. Accordingly, the 1 H NMR studies suggest that both complexes are stable in solution, and, therefore, that the transformation of complex 1 into 2·1.75H 2 O is mediated by the presence of the dysprosium(III) nitrate.

Single X-ray Diffraction Studies
Single crystals of [Zn 2 L 2 (NO 3 ) 2 ]·1.75H 2 O (2·1.75H 2 O) were obtained as detailed above. An ellipsoid diagram for 2 is shown in Figure 3, and the main distances and angles are recorded in Table 1 Single crystals of [Zn2L 2 (NO3)2]·1.75H2O (2·1.75H2O) were obtained as detailed above. An ellipsoid diagram for 2 is shown in Figure 3, and the main distances and angles are recorded in Table 1.  The unit cell of 2·1.75H2O contains neutral dinuclear [Zn2L 2 (NO3)2] molecules and water as solvate. [Zn2L 2 (NO3)2] has an inversion center, which makes both halves of the molecule equivalent. In this complex, the new dianionic ligand [L 2 ] 2− acts as a dinucleating octadentate donor, providing an N3O (Nimine, Namine, Npiperazine and Ophenolate) environment for each Zn II ion, with the methoxy oxygen atoms remaining uncoordinated. The metal centers reach their coordinative saturation with a nitrate group, linked in a bidentate chelate mode. Accordingly, both Zn II ions are hexacoordinated, with distances and bond angles that agree with a distorted octahedral geometry. It should be emphasized that the distortion of the octahedron is considerable, since an angle close to 55° is observed (Table  1), a value much lower than what would be expected, but that is quite typical for bidentate chelate nitrates [12]. Both zinc ions are bridged through the NCCN fragment of the piperazine ring, which adopts a chair conformation, leading to a Zn···Zn intramolecular distance of ca. 5.9 Å. The dinuclear [Zn2L 2 (NO3)2] units are connected between them through hydrogen bonds, where only the amine nitrogen atoms (N2) and the water solvate are implicated, and the shortest Zn···Zn intermolecular distance in this arrangement is ca. 8.09 Å.   2 ] has an inversion center, which makes both halves of the molecule equivalent. In this complex, the new dianionic ligand [L 2 ] 2− acts as a dinucleating octadentate donor, providing an N 3 O (N imine , N amine , N piperazine and O phenolate ) environment for each Zn II ion, with the methoxy oxygen atoms remaining uncoordinated. The metal centers reach their coordinative saturation with a nitrate group, linked in a bidentate chelate mode. Accordingly, both Zn II ions are hexacoordinated, with distances and bond angles that agree with a distorted octahedral geometry. It should be emphasized that the distortion of the octahedron is considerable, since an angle close to 55 • is observed (Table 1), a value much lower than what would be expected, but that is quite typical for bidentate chelate nitrates [12]. Both zinc ions are bridged through the NCCN fragment of the piperazine ring, which adopts a chair conformation, leading to a Zn···Zn intramolecular distance of ca. 5.9 Å. The dinuclear [Zn 2 L 2 (NO 3 ) 2 ] units are connected between them through hydrogen bonds, where only the amine nitrogen atoms (N2) and the water solvate are implicated, and the shortest Zn···Zn intermolecular distance in this arrangement is ca. 8.09 Å.

Conclusions
This work reports the uncommon conversion of an imidazolidine ligand into a piperazine donor in the presence of a dysprosium(III) salt. Accordingly, herein is described the first piperazine heterocycle isolated from an imidazolidine ligand in the presence of a lanthanoid metal ion.