Syntheses of Nickel (II) Complexes from Novel Semicarbazone Ligands with Chloroformylarylhydrazine, Benzimidazole and Salicylaldehyde Moieties

This study addressed the design and syntheses of diverse ligands, which were then successfully treated with Ni (II) ion to afford a series of nickel complexes. α-Chloroformylarylhydrazine hydrochlorides 6 contain two different functional groups. One is a strong nucleophile, and the other is a good electrophile. Therefore, it can be designed to react with several reagents to obtain diverse derivatives which can be used as ligands for metal complexes. Furthermore, benzimidazole and salicylaldehyde can provide electron donor sites, N and O electron donors, separately. Hence, the starting materials α-chloroformylarylhydrazine hydrochlorides 6 were first treated with 2-(aminomethyl)-benzimidazole (7) to give the corresponding semicarbazides 8. Then, the semicarbazides 8 reacted with various substituted salicylaldehydes 9–11 to afford the desired substituted-salicylaldehyde 2-aryl-4-substituted semicarbazones 12–14, which could coordinate with nickel (II) ion to give the corresponding nickel complexes 15–17.


Introduction
The design and synthesis of metal-organic frameworks have attracted much attention from chemists. Thiosemicarbazones, semicarbazones and their metal complexes have been extensively studied in recent years, mainly because of their potential biological properties [1][2][3]. However, less attention has been devoted to the synthesis of the structurally analogous semicarbazones and their metal complexes. Semicarbazones are readily available and can coordinate to the metal ion either as neutral or deprotonated ligands through two or three donor atoms. In order to obtain novel ligands containing semicarbazone moieties, adequate precursors should first be designed and investigated. 3-Arylsydnones 1 could be cleaved and hydrolyzed to α-formylarylhydrazine hydrochloride intermediates by hydrochloric acid, and then the intermediates were sequentially converted to 3-arylhydrazine hydrochlorides 2 [4]. However, 3-phenyl-4-methylsydnone (3) was only hydrolyzed to α-acetylphenylhydrazine (4) by hydrochloric acid [5]. According to the above result, we considered treating 3-arylsydnones 1 with N-chlorosuccinimde (NCS) to obtain 3-aryl-4-chlorosydnones 5 which could further react with hydrochloric acid to afford α-chloroformylarylhydrazine hydrochlorides 6, as shown in Scheme 1. The precursors 6 would be expected to react with appropriate amines and aldehydes to afford various Schiff-bases which contained the desired semicarbazone moieties.  α-Chloroformylarylhydrazine hydrochlorides 6 contained two different functional groups. One is a very strong nucleophile, and the other is a good electrophile [6]. Precursors 6 could be treated with several reagents to give diverse derivatives [7]. We have already done abundant research on numerous aspects of 3-arylsydnone derivatives [8][9][10][11][12][13][14][15], and this is the first work conducted to utilize the starting materials 6, which are derived from the decomposition of sydnone compounds, to synthesize diverse ligands and transition metal complexes.

Synthetic Chemistry
Starting materials 6, since they contain acyl chloride groups, are very active and moisture-sensitive. We thus first dealt with the acyl chloride group of precursors 6 in the novel ligands design, and then dealt with the amino group to obtain the desired ligands. The benzimidazole scaffold is a useful structural motif for imparting chemical functionality to biologically active molecules [16][17][18][19][20], and many metal complexes with benzimidazole moieties display a wide range of special activities [21][22][23]. 2-(Aminomethyl)benzimidazole (7) can provide N,N two electron donor atoms, therefore, the starting materials 6a-c were first treated with benzimidazole 7 at 0 °C in the presence of triethylamine to give the corresponding 2-aryl-4-[(1H-benzo[d]imidazol-2-yl)methyl]semicarbazides 8a-c, as shown in Scheme 2. Because the starting materials 6 have a tendency to dimerize, the desired reactions must be carried out at 0 °C, otherwise, the efforts would fail. All the semicarbazides were synthesized in good yields and analytically pure. Among them, single crystals of 8a and 8b were suitable for X-ray structural analyses. Figures 1 and 2 display the ORTEP drawings of semicarbazides 8a and 8b. Based on the X-ray data, semicarbazide 8b was crystallized with a water molecule, and formed hydrogen bonds between the N4 atom and H2O because the N4 and O2 distance was 2.724 Å.  It was considered that the novel semicarbazides could be reacted with various salicylaldehydes to form the well-known hydrazone Schiff bases. Salicylaldehyde hydrazone Schiff base have long received considerable attention for their fascinating chemical behavior and biological activity. Of interest to chemists is the coordination ability of salicylaldehyde hydrazone ligand through the imine nitrogen and phenoxy oxygen electron-donating atoms that allow it to serve as a multidentate ligand in structural assemblies [24][25][26][27][28][29]. In this study, the synthesized semicarbazides 8a-c were treated with various substituted salicylaldehydes, such as salicylaldehyde (9), 5-chlorosalicylaldehyde (10) and 4-methoxysalicylaldehyde (11) to afford a series of corresponding substituted-salicylaldehyde 2-aryl-4-[(1H-benzo[d]imidazol-2-yl)methyl]semicarbazones 12a-14c. The semicarbazones 12a-14c with salicylaldehyde-acylhydrazone moieties could coordinate with nickel (II) metal ion to give novel transition nickel (II) complexes 15a-17c as shown in Scheme 2. The novel synthesized ligands 12-14 and metal complexes 15-17 were identified by IR, NMR, ESIMS, EA and X-ray crystallography.

IR and NMR Studies
Based on the IR studies, the O-H and N-H stretching frequencies observed at around 3400 and 3200 cm −1 in free semicarbazones 12-14 are found to be absent in the complexes 15-17. The result confirms the deprotonation of these ligands upon metal complexation. Similarly, in the NMR studies, the signals at approximately 8.4 ppm (triplet, J = 5.6 Hz, 1H, NH) and about 10.0 ppm (singlet, 1H, OH) were originally assigned to the NH and OH protons of the semicarbazone. However, the signals are not found in the spectra of the nickel complexes 15-17. In addition, the NMR signal of CH2 in the semicarbazones is at about 4.6 ppm (doublet, J = 5.6 Hz, 2H), and is split into a doublet by coupling with the neighboring NH proton. However, the NMR signal of CH2 is a singlet without any neighboring NH proton coupling in the metal complexes. Figures 3 and 4 show the NMR spectrum of ligand 13a and the corresponding complex 16a, respectively. All the above results indicated that semicarbazone ligands 12-14 served as deprotoned ligands after losing two protons from the NH and OH groups upon metal complexation, and 2-(aminomethyl)benzimidazole (7) and substitutedsalicylaldehydes 9-11 might provide electron donor sites, N, N and O electron donor atoms.

MS Study
To further confirm the molecular formula of nickel complexes 15-17, Fourier-Transfer Mass Analyzer was used to get the low resolution and high resolution ESI mass spectral data. The obtained analysis results definitely confirmed the molecular formulas of the synthesized complexes 15-17. The low-resolution ESIMS spectra of all nickel complexes 15a-c and 17a-c show distinct m/z [M+H] + and [M+2+H] + peak patterns because the relative isotope abundances of elemental nickel are 58 Ni (68.0769%), 60 Ni (26.2231%), 61 Ni (1.1399%), 62 Ni (3.6435%) and 64 Ni (0.9256%). Besides, the relative isotope abundances of the element chlorine are 35 Cl (75.76%) and 37 Cl (24.24%), nickel complexes 16a-c containing one chlorine element would show more complicated MS peak patterns.

X-ray Study of Ligands and Complexes
All the new semicarbazones and complexes were synthesized in good yields and analytically pure. Among them, the crystals of 12a and 16a were suitable for X-ray structure analyses. Figures 5 and 6 show the ORTEP drawings of semicarbazone 12a, and Ni complex 16a, respectively. Based on the ORTEP drawing of semicarbazone 12a ( Figure 5), we confirm that the electron donor sites N(1), N(3), N(5) of free semicarbazone ligands 12-14 show a Z, Z configuration about N(2)-C(1), C(2)-C(3), and the hydroxyl oxygen is anti to the imine nitrogen N(1). However, the nickel complex 16a was crystallized with the salicylaldehyde hydroxyl oxygen syn to the imine nitrogen, as shown in Figure 6. According to the X-ray diffraction analyses, during metal complexation, semicarbazones 12-14 behave as tetradentate and deprotonated ligands after losing two protons from the OH and NH groups (Scheme 2), and form one six-and two five-membered chelate rings around the central metal through a set of donor atoms that consists of the salicylaldehyde hydroxyl oxygen, imine nitrogen, and two nitrogens of 2-(aminomethyl)benzimidazole ( Figure 6).    (2). The result indicates that the tricyclic N,N,N,O ring system forms a nearly square planar structure around the nickel atom, and contributes to the stability of the complex 16a. The ORTEP drawings of the metal complexes and diffraction data showed that the synthesized semicarbazones were tetradentate and dideprotoned ligands upon metal complexation. The nickel complex 16a was crystallized with a water molecule, but there is no hydrogen bond between the N4 atom and H2O. Figure 7 displays the packing diagram of complex 16a. The crystallographic data of semicarbazides 8a and 8b are summarized in Table 1. Table 2 lists the crystallographic data of semicarbazone 12a and complex 16a.

General Information
All melting points were determined on an England Electrothermal Digital Melting Point apparatus and were uncorrected. IR spectra were recorded on a Mattson/Satellite 5000 FT-IR spectrophotometer. Mass spectra were measured on a high-resolution JEOL JMS-700 mass spectrometer and a Bruker APEX II FT-MS. 1 H-NMR spectra were run on a Bruker AV 400 NMR spectrometer, using TMS as an internal standard. 13 C-NMR spectra were recorded out with complete 1 H decoupling and assignments were made through additional DEPT experiments. Elemental analyses were taken with an Elementar Vario EL-III Analyzer. X-ray crystallography was performed on a Nonius CAD4 Kappa Axis XRD instrument. α-Chloroformylarylhydrazine hydrochlorides 6a-c were prepared from the corresponding 3-aryl-4-chlorosydnones 5a-c according to the literature [6].

Syntheses of 2-aryl-4-[(1H-benzo[d]imidazol-2-yl)methyl]semicarbazides 8a-c
To an ice-cooled solution of α-chloroformyl phenylhydrazine hydrochloride (6a, 207.1 mg, 1.0 mmol) in ethyl acetate (2 mL), an ice-cooled solution of 2-(aminomethyl)benzimidazole dihydrochloride hydrate (7, 242.2 mg, 1.1 mmol) in ethyl acetate (2 mL) was slowly added. Then, triethylamine (454.5 mg, 4.5 mmol) was added dropwise to the above solution. The mixed solution was stirred at 0 °C for about 6-7 h until the reaction was complete. The precipitating solid was first collected by filtration, and the organic filtrate was kept for the next step. First, the filtered solid was added to cold water (5 mL) with stirring and filtered to remove the dissolved triethylamine hydrochloride salt, then 261.5 mg of white crude product was obtained. Next, the organic filtrate was evaporated to near dryness and cold 2-propanol (1 mL) was added to precipitate a solid after stirring and filtration, and 21.2 mg of white solid were thus obtained. All the solid products were combined and recrystallized from dichloromethane/2-propanol to afford 221.9 mg (0.79 mmol, yield 79%) of 8a as white crystals. The chemical and physical spectral characteristics of these products 8a-c are given below.  Table 1. Further details have been deposited at the Cambridge Crystallographic Data Center and allocated the deposition number CCDC 959867.