International Journal of Pharmtech Research

International Journal of PharmTech Research CODEN( USA): IJPRIF ISSN : 0974-4304 Vol.1, No.2, pp 304-309, April-June 2009

Synthesis and Computational Verification of New Nickel(ІІ) Complexes

Nabil M. El-Halabi1*, Adel M. Awadallah1, Fakhr M Abu-Awwad1, Zaki S. Safi2 1,Department of Chemistry, The Islamic University of Gaza, Gaza, Palestine. 2,Department of Chemistry, Al Azhar University of Gaza , Gaza, Palestine. E-mail*: [email protected]

Abstract: Nitrilimines 7 generated in situ from the respective hydrazonyl chlorides are found to react with benzhydrazide 8 at room temperature to give the corresponding 2,3,5,6-tetraza-4-hexen-1-one 9. The reaction of 9a with nickel(ІІ) acetate tetrahydrate, in two to one mole ratio in ethanol at room temperature overnight, gave poor yield of square planar complex with a five-membered rings 10a. The new compounds 9a, 9b and 10a were characterized and identified by IR, 1H NMR, 13C NMR and MS spectra. Computational procedures at B3LYP/6-31G(d) level of theory were used to verify the suggested structure of the complex 10a employing both thermodynamic properties and geometrical features of both reactants and products. Keywords: nickel; tetraza-4-hexen-1-one; benzhydrazide; B3LYP; energy profile.

Introduction: Quit recently, Some new metal(II) complexes, ML2 [M = Recently, we have reported the synthesis of Mn, Co, Ni, Cu and Zn] of 2- square planar metal complexes with substituted 1,2,4- acetylpyridinebenzoylhydrazone 1 containing triazoleoximes1 hydrazones2 and substituted 1,2,4,5 trifunctional N, N, O-donor system have been tetrazineoximes3 . In all these works, we have N,N- synthesized, and two of them were crystallographically bidentate ligands that lead to the formation complexes characterized4 . with five or six membered rings.

R N Ar R N H N Ar N O N M N O N O N 1-3 N Ar R 4-6 Entry 1/4 2/5 3/6

Ar N NH2

R CH3 H H Nabil M. El-Halabi et al /Int.J. PharmTech Res.2009,1(2) 305

Selected first-row transition metal complexes 4-6. Theoretical calculations that support the suggested with 2-pyridinecarbaldehyde isonicotinoylhydrazone 2 structure will be presented. and 2-pyridinecarbaldehyde (4'- Results and discussion: aminobenzaldehydehydrazone) 3 were recently The compounds 9a, b are readily accessible via synthesized by Bernhardt et al in an attempt to design and the reaction of the corresponding nitrilimines 7 with synthesis of ligands that exhibit high Fe chelation benzhydrazides 8 overnight at room temperature. The efficacy5 . It was found that, divalent first-row transition assignments of structure 9a, b are based on spectral data. metals (Mn, Fe, Co, Ni, Cu and Zn) readily form bis The IR spectrum of 9a in KBr revealed the (complexes) with the above ligands with each ligand presence of two NH absorption peaks at 3298 and 3280, coordinated meridionally through its pyridine-N, imine-N and two C=O absorption peaks at 1681 for CH3C=O and and carbonyl-O atoms, forming distorted octahedral cis- 1640 for NH-NHC=O. The IR spectrum of 9b revealed MN4O2 complexes. the presence of two C=O absorption peaks at 1716 for In this work, ligands containing nitrogen and CH3OC=O and 1646 for NH-NHC=O. oxygen atoms 9 will be prepared from the reaction of The electron impact mass spectra of 9a, b nitrilimines 7 with benzhydrazides 8. The complexation display the correct molecular ions in accordance with the behavior of these ligands will be investigated. Since those suggested structures. ligands contain many possible coordinating sites, they The 1H-NMR spectra of both compounds show three N-H may react as N,N-bidentate ligands leading to square signals in addition to the signals of the methyl groups and planar complexes , or as N,N,O-tridentate ligands leading the aromatic protons. to octahedral complexes similar to the above complexes Scheme 1:

R R H H N Ph N N Ph N N Cl Et3N H2N H NH + NH O Ar O Ar 9a,b 7a,b 8

Ni(OAc)2.4H2O

O Ph R R R NH N Ar N NH Ph N N N NH Ar N NH N O N O Ar Ar Ni O Ni Ar Ar Ni N NH N Ar N O NH N Ph HN N HN N N N Ar R R Ph O R 10a 11a 12a

Entry 7a/9a/10a/11a 7b/9b/10b/11b

Ar Cl Cl

R C(O)CH COOCH 3 3 Nabil M. El-Halabi et al /Int.J. PharmTech Res.2009,1(2) 306

13C-NMR spectra display the characteristic signals of the In order to obtain more reliable energies for the suggested structure. Two C=O signals appear in addition local minima, final energies were evaluated by using the to the methyl signals and the signals of the aromatic same functional combined with the 6-31+G(d,p) basis set carbons. for all atoms except for Ni2+, where the (14s9p5d/9s5p3d) The reaction of 9a with nickel(ІІ) acetate tetrahydrate, in basis set of Wachters11 and Hay12 was used, two to one mole ratio in ethanol at room temperature supplemented with a set of (1s2p1d) diffuse functions overnight, gave poor yield of a green complex. The and with two sets of f functions and one set of g assignment of the complex structure was based on functions. It has been shown that this approach is well spectral data. suited for the study of this kind of systems, yielding The IR spectrum of the complex shows two C=O beaks at binding energies in good agreement with experimental almost the same positions of compound 9a, and one NH values. peak disappeared. This is evident of N,N-complexation of The corresponding Ni2+ binding energies, D0, were the ligands and excludes the tridentate N,N,O-octahedral evaluated by subtracting from the energy of the complex complex 12a. the energy of the neutral and that of Ni2+, after including The electron impact mass spectrum of the nickel(II) the corresponding ZPE corrections scaled by a factor of complex display the correct molecular ion for an ML2 0.9806 [13]. Enthalpies and Gibbs free energies have complex. been evaluated by considering the thermal corrections at The electrical conductance of the complex in DMF is 298.15 K and the values obtained for the entropy by almost negligible supporting its non-electrolytic nature. using the harmonic vibrational frequencies. The electronic spectrum of the Ni(II) complex display a In this computational procedures, the structures -1 1 1 distinct band around 20408 cm assigned to A1g → B1g 10a and 11a are expected equally as products from the 6 transition in planar field . direct interaction of Ni(CH3COO)2.2H2O with the ligand The complex was assigned structure 10a in which the 9a, (Scheme 1). Both structures are local minima of the ligand acts as N,N-bidentate ligand forming a complex PES with all harmonic frequencies being real. A single with five membered rings. The assignment is based on point calculation at B3LYP/6-31+G(d,p) level of theory the fact that five-membered rings are more stable than the have been carried out, where it is repeatedly reported that six-membered rings7 , and no metallation occurs with the for similar huge structures, this level of theory presents a hydrazidic NH. This structure assignment was further good correlation with the attained experimental results. supported by computational calculations. The detailed IR, The corresponding relative H, E and G are displayed in 1H-NMR, 13C-NMR and MS data are presented in the Table 1. The corresponding total energies, zero point experimental part. energies corrections, ZPEC, thermal correction to Computational Procedures and Results: enthalpies, TCH, and entropies, S, are listed in Table S1 In this work, the density functional theory (DFT) of the supplementary material. The optimized geometries is used to investigate the reaction depicted in scheme (1). of 5a and 6a are given in Figure 1. The hybrid gradient corrected exchange functional As revealed from data of the relative energy proposed by Becke 8 combined with the gradient- calculations listed in table 1, an interaction of Ni2+ with corrected correlation functional of Lee, Yang, and Parr9 the nitrogen atoms (Ns) at positions 1 and 3 to form (B3LYP) in Gaussian 03 software10 is employed along complex 10a is of a big significance, when compared to with 6-31G(d) basis set. B3LYP has been extensively the case of 11a, in which the metal interacts with Ns at employed in similar computational procedures and turned positions 1 and 4. Obviously, complex 10a is much more out to be quite reliable for geometrical optimizations. stable than its rival 11a by about 196.5 kJ/mol. This large Structures 9a, 9b, 10a, and 11b in scheme (1) difference in the structures’ relative energies doubtlessly were fully optimized to obtain structural, electronic and conclude that under normal conditions of reaction in the energetic information. The harmonic vibrational gas phase, complex 10a is predominant while complex frequencies were also calculated at the same level of 11a can't be initially formed. theory to ensure that each stationary point corresponds to Similarly, the geometrical parameters as may be a true local minimum on the potential energy surface concluded from the optimized structures presented in (PES), and to estimate the zero-point energy (ZPE) Figure 1 can assure and explain the further stability of corrections. Relative energies were computed by complex 10a over complex 11a. The former exhibits a subtracting the most stable energy after including the symmetric structure of two almost regular pentagons with corresponding ZPE corrections scaled by an empirical Ni atom in common, where the counterpart bond lengths factor of 0.9806. Also, Enthalpies and Gibbs energies are closely equal and the sums of the interior angles are were calculated by considering the thermal corrections at 539.2o and 539.5o, with only about 0.5o away from the 298.15 K and the values obtained for the entropy by well defined pentagons. Meanwhile, structure 11a shows using the harmonic vibrational frequencies. irregular squeezed hexagonals with different counterpart bond lengths and much smaller interior angles than expected (672o, and 689.2o). Additionally, in 10a the Ni- Nabil M. El-Halabi et al /Int.J. PharmTech Res.2009,1(2) 307

Figure 1: Optimized Geometries of Complex 10a and 11a Nabil M. El-Halabi et al /Int.J. PharmTech Res.2009,1(2) 308

N bond lengths are shorter than their counterpart Structure 10a was evident based on spectral data. bonds formed in complex 11a with. Computational procedures at the B3LYP/6- 31+G(d,p)//B3LYP/6-31G(d) level of theory have Conclusion: presented other several indications supporting the experimental findings.

Table 1: calculated energies (KJ/mol), HOMO, LUMO (au) at B3LYP/6-31G

species ΔE ΔH ΔS ΔG 10a 0.00 0.00 0.00 0.00 11a 169.51 169.61 0.02 169.64

Supplementary Information

S1: Calculated energies, corrections, and entropies at B3LYP/6-31G

E1 E2 ZPEC TCH S 10a -4403.68745 -4403.836918 0.564554 0.609129 268.16 11a -4403.62567 -4403.771701 0.563948 0.608562 268.14

E1 = B3LYP/6-31(d) E2 = B3LYP/6-31+(d,p)

Experimental: 114.8, 127.5, 129.4, 132.3, 132.4 (5 signals, 9CH for Melting points were determined on an aromatic carbons), 124.3, 128.9, 139.6 (3 signals, 3C for Electrothermal Melting Temperature apparatus and are aromatic carbons); MS, m/z (%) 330 (M+), 211 (M+- uncorrected. The infrared spectra were obtained using C9H9N3OCl), 105 (ph(C=O)), 77 (ph), 43 (CH3(C=O)). Perkin-Elmer 237FT-IR spectrophotometer (KBr discs). 1H and 13C NMR spectra were recorded on a Brucker 6-(4-chlorophenyl)-4-methoxycarbonyl-1- phenyl- 300MHz instrument for solutions in DMSO or CDCl3 at 2,3,5,6-tetraza-4-hexen-1-one (9b) 25oC, using TMS as an internal reference. The Mass The yield of pure product was indicated by TLC; yield spectra were run on MTA 112 Mass spectrometer. 2.7g (78%), yellow, mp 1790C; IR (KBr) 3296.2 (-(- NH-Ar), 3264.3 (NH(C=O)ph), 1715 ((C=O)OCH3), Reaction of hyrazonoyl chlorides with 1645 (NH-NH(C=O)ph), 1598 (C=N); 1HNMR δ 3.9 (s, benzhydrazide 3H, CH3(OC=O)), 10.4 (s, 1H, -NH(C=O)ph), 8.1 (s, 1H, Hydrazonoyl chlorides 7 (0.02 mol) and benzhydrazide 8 =N-NH-C6H4Cl), 7.1-7.9 (10H, one of -NH-NH(C=O)ph (3.2g, 0.024 mol) were dissolved in tetrahydrofuran (100 and 9 for aromatic protons); 13C NMR  53.4 mL). Triethylamine (4 mL) was added and the mixture (CH3O(C=O)), 170 ((C=O)OCH3), 165 (HN(C=O)ph), was then stirred over night for 48 hours. The solvent was 115.8, 127.4, 129.3, 129.6, 133.0 (5 signals, 9CH for then evaporated, and the residual solid was washed with aromatic carbons), 127.3, 127.6, 141.5 (3 signals, 3C for water to remove the triethylamine salt. The crude product aromatic carbons); MS, m/z (%) 346 (M+), 226 (M+- was recrystallized from ethanol (40 mL). C9H9N3O2Cl).

4-Acetyl-6-(4-chlorophenyl)-1-phenyl-2,3,5,6-tetraza- Synthesis of bis (4-acetyl-6-(4-chlorophenyl)-1-oxo- 4-hexen-1-one (9a) 1-phenylhexan-2, 3, 5, 6-tetraza-4-ene) Nickel(ІІ) The yield of pure product was indicated by TLC; yield complex 10a 4.06g (61.43%), yellow, mp 1820C; IR (KBr) 3298.2 -(- To a solution of 4-acetyl-6-(4-chlorophenyl)-1-oxo-1- NH-Ar), 3280 (NH(C=O)ph), 1681 ((C=O)CH3), 1640 phenylhexan-2, 3, 5, 6-tetraza-4-ene 0.66g (2.0 mmol) in (NH-NH(C=O)ph), 1597 (C=N); 1HNMR δ 2.5 (s, 3H, (25 mL) ethanol was added a solution of nickel(ІІ) CH3(C=O)), 10.2 (s, 1H, -NH(C=O)ph), 9.7 (s, 1H, =N- acetate tetrahydrate 0.248g (1 mmol) in ethanol (25 mL). NH-C6H4Cl), 7.1-7.9 (10H, one of -NH-NH(C=O)ph The resulting reaction mixture was stirred overnight at and 9 for aromatic protons); 13C NMR  24.4 room temperature for 72 hours. The deep green solid (CH3(C=O)), 192.2 ((C=O)CH3), 166.4 (HN(C=O)ph), product was collected by suction filtration, washed with cold ethanol (5 mL) and dried in vacuo. The yield of the Nabil M. El-Halabi et al /Int.J. PharmTech Res.2009,1(2) 309 pure product was indicated by TLC, yield .150 mg (16.52 [8] Becke, A. D. J. Chem. Phys. 1992, 96, 9489; %), mp over 300; IR (KBr) 3326.3 (NH- Becke, A. D. J. Chem. Phys. 1993, 98, 1372. NH(C=O)ph),1680.8 ((C=O)CH3), 1646.4 (NH- [9] Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B: NH(C=O)ph), 1599 (C=N); 1HNMR δ 2.3 (s, 6H, Condens. Matter 1988, 37, 785. 2CH3(OC=O)), 8.9 (s, 2H, -2NH(C=O)ph), 7.3-8.9 (20H, [10] Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; two of -NH-NH(C=O)ph and 18 for aromatic protons); Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; 13 C NMR  29.8 (CH3(C=O)), 200.1 ((C=O)CH3), 165.8 Montgomery, J. A.; Jr., T. V.; Kudin, K. N.; (HN(C=O)ph), 122.4, 127.2, 129.5, 132.6, 132.8 (5 Burant, J. C.; Millam, J. M.; Iyengar, S. S.; signals, 18 CH for aromatic carbons), 122.4, 130.0, 134.1 Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; (3 signals, 6C for aromatic carbons); Scalmani, G.; Rega, N.; Petersson, G. A.; MS, m/z (%) 719.20 (M+.-Ni(C16H14ClN4O2)2). Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, References: T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; [1] Ferwanah, A. R. S.; Awadallah, A. M.; Awad, B. Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; M.; El-Halabi, N. M.; Boese, R. Inorganica Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, Chimica Acta 2005, 358, 4511-4518. R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; [2] Awadallah, A. M.; Ferwanah, A. R. S.; Awad, B. Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, M.; El-Halabi, N. M. Transition Metal P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Chemistry 2004, 29, 280-283. Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, [3] Awadallah, A. M.; Ferwanah, A. R. S.; Awad, B. S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; M.; El-Halabi, N. M. Asian Journal of Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Chemistry 2002, 14, 1235-1240.. Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. [4] El-Halabi, N. M.; Awadallah, A. M.; Faris, W. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; M.; Seppelt, K.; Shorafa, H. unpublished results. Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, [5] Bernhardt, P. V.; Armstrong, C. M.; Chin, P.; I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al- Richardson, D. R. Eur. J. Inorg. Chem. 2003, Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; 1145-1156 Challacombe, M.; Gill, P. M. W.; Johnson, B.; [6] Cotton, F. A.; Wilkinson,G.; Gaus, P. L. Basic Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. Inorganic Chemistry, 3rd. ed, John Willey & Sons A. In Gaussian 03; Revision C.02 ed.; Gaussian, Inc., New York, 1995, p. 574. Inc.: Wallingford CT, 2004. [7] Owen, S. M.; Brooker; A. T. A Guide to Modern [11] Wachters, A. J. H. J. Chem. Phys. 1970, 52, Inorganic Chemistry, 1st ed, Longman group, 1033-1036. Singapore 1994, p. 192 – 193. [12] Hay, P. J. J. Chem. Phys. 1977, 66, 4377-4384. [13] Scott, A. P.; Radom, L. J. Phys. Chem 1996, 100, 16502-16513.