1. INTRODUCTION:

Preparation of Schiff base metal complexes received increasing interest owing to their versatile coordination behaviour and in the understanding of molecular processes [1-3]. Schiff base metal complexes are of noteworthy attention in terms of its structural and coordination chemistry. They show diverse chemical, optical and magnetic properties by tailoring with diverse ligands. In particular, the study of metal complexes of Schiff base (SB) ligands seems to be attractive in terms of uncommon structure and stability. SB complexes are considered to be among the most significant stereochemical models in transition metal coordination chemistry due to their preparative accessibility and structural diversity [4,5].

Structurally, a Schiff base (SB) (also known as imine or azomethine) is a nitrogen analogue of an aldehyde or ketone in which the carbonyl group (>C = O) is replaced by an imine or azomethine group [6]. Schiff base metal complexes which typically contain nitrogen, sulphur or oxygen as ligand atoms have become progressively important because these SB can bind with different metal centres involving several coordination sites and permit successful synthesis of metal complexes [7]. The extraordinary affinity for the chelation of the SB towards the transition metal ions is exploited in synthesizing their solid complexes [8]. The interaction of these donor ligands and metal ions gives complexes of different geometries and literature survey exposes that these complexes are biologically active compounds [9-11]. Thus, currently, SB and their metal complexes have attained much attention of researcher because of their extensive biological activities [12,13].

The advances in inorganic chemistry deliver better openings to use SB metal complexes as therapeutic agents. Research has shown momentous improvement in utilization of SB transition metal complexes as drugs to treat numerous human diseases. The use of SB transition metal complexes as therapeutic compounds has become more and more pronounced. Synthetic SB metal complexes are an developing class of compounds with varying chemistry, different molecular topologies and sets of donor atoms. It is a known fact that N atom plays a crucial role in the coordination of metals as the active site of numerous metallobiomolecules [12-14]. These complexes offer a great variety in their action; as antibacterial [14-16], antifungal [17,18], anticancer [19, 20] and anti-inflammatory agents [21,22]. Due to the appeal of new metal-based antibacterial compounds, Schiff base metal chemistry is becoming an emerging area of research.

Schiff base metal complexes are efficient catalysts both in homogeneous and heterogeneous reactions [23-25] and the activity of these metal complexes varied with the type of ligands, coordination sites and metal ions [26]. Catalytic activities of Schiff base metal complexes are plentifully found in literature. In this regard, more selective behavior of Schiff base complexes has been observed for a number of reactions like hydroxylation, oxidation, epoxidation and aldol condensation.

On the other hand, acetylacetone is an organic compound that excellently exists in two tautomeric forms that rapidly interconvert. It worked as a building block for the preparation of heterocyclic compounds. It may undergo condensation reaction between its ketone moiety and that of amine group of amino acid to form the desired ligand with azomethine (-HC=N-) linkage [27]. The chemistry of Schiff bases and their metal complexes have gained attraction of the interest of researchers despite their vast report in literature [28]. These are connected to the adaptability of these compounds in inorganic synthesis as well as their several applications in biology [29], pharmacology [30] and industries [31] etc.

This review goes over the main biological and catalytic applications of Schiff bases derived from acetylacetone and their complexes.

2. BIOLOGICAL ACTIVITY:

2.1 Antibacterial Activity:

A series of amino acid-derived Schiff base (Figure-2) and their cobalt (II), copper (II), nickel (II), and zinc (II) metal complexes have been synthesized by Zahid H. Chohan et al. Ligands were derived by the condensation of β-diketones with glycine, phenylalanine, valine, and histidine and act as bidentate towards metal ions via the azomethine-N and deprotonated-O of the respective amino acid. All the synthesized ligands as well as the metal complexes (Figure-2.1) were tested for their antibacterial activity against six human pathogenic bacteria Escherichia coli, Shigella ﬂexeneri, Pseudomonas aeruginosa, Salmonella typhi, Bacillus subtilis and Staphylococcus aureus bacterial strains and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus ﬂavus, Microsporum canis, Fusarium solani, and Candida glaberata. The results of these studies show the metal (II) complexes to be more antibacterial/antifungal against one or more species as compared to the free ligands [32].

Figure 2: Proposed structure of the ligands

Figure 2.1: Proposed structure of the complexes

The Schiff base ligand was synthesized by the condensation of 4 (diethyl amino)-2-hydroxy benzaldehyde (10mmol) and 4-nitrobenzohydrazine (10mmol) in methanol solvent by CHARITY W. DIKIO et al. Complexation was performed by with the synthesized ligand and cobalt (II), Manganese (II), Magnesium (II) salts of acetylacetone derived from metal hydroxide and acetylacetone. Potentiality of the synthesized ligand and complexes as antibacterial agent was assessed against two bacteria Staphylococcus aures and Entarococcus faecails. The outcome of these studies demonstrated that Mn (II) complex show higher antibacterial activity than other complexes and the ligand itself [33]. The ligands were derived from acetyl acetone with aniline, 2-aminophenol, para anisidine and hydrazine hydrate (figure 2.2 and 2.3)

Figure 2.2: 4-(2-hydroxyphenylimino) pentan-2-one

Figure 2.3: 4-(Phenylimino)Pentan-2-One

by the condensation method in methanolic solvent medium by A. V. G. S. Prasad et al.. Further antibacterial and antifungal activity of these derived ligands have been evaluated against Bacillus subtilis and candida. It has been find that, among the synthesized ligands, 4-(phenylimino) pentan-2-one exhibit highest activity in both cases with respect to the other ligands. In addition to this it show more activity against the selected bacteria and fungi species than the standard drug amoxicillin and moconazole respectively [34].

A series of ligands were derived from the Condensation of 2-hydroxy1-naphthaldehyde or acetyl acetone with various amino-acids like; glycine , b-alanine , DL-valine, DL-4-aminobutyric acid , L-methionine , L-leucine and phenylglycine by Mala Nath et al. Condensation of derived Schiff bases with dibutyltin(IV) oxide as 1:1 molar ratio gives complexes of dibutyltin(IV).An attempt has been made to test antibacterial and antifungal activity of the resulting complexes against some bacteria species streptococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and fungi species candida albicans, Cryptococcus neoformans, Sporotrichum schenckii, Trichophyton mentagrophytes and Aspergillus fumigatu .The result of these studies have revealed that metal complexes that were synthesized from Schiff base of 2-hydroxy-1-naphthaldehyde and amino acids tend to exhibit greater activity towards the bacteria and fungi than which derived from the acetylacetone and amino-acids [35].

Synthesis of the ligands was carried out via two steps by Wageih G. Hanna and Mona M. Moawad. First step was followed by the formylation of 8-hydroxyquinoline -5-sulphonic acid according to Sein and Ray method and second step was the assymetric ligand formation step executed by the Diehi and Hach method. Metal complexes were prepared by adding aqueous solution of Co (II), Ni (II), Cu (II) perchlorates (0.001M) to the etanolic solution of ligands (0.001M) that was previously dissolved and NaOH (0.002M) was also added to make the ligands ionic. Antibacterial and antifungal activity of all the derived complexes, ligands and metal salts were done for comparative studies. It was accomplished on gram negative (Sercina lueta) and gram positive (Escherichia coli) bacteria and two fungi aspergillous niger and candida albicians .From the study of Minimal Inhibitiory Concentration(MIC) zone an assignment has been made that uncomplexed ligands show greater activity when it complexed with the metal salts due to the chelate formation. Complexes in the form of chelate may penetrate the cell wall of fungi and converted to half chelate immediately by dissociation. Thus, half chelate might be a toxic component by binding or blocking the existing metal substances located on enzymes. From that point of view, Cu complex has the lowest MIC value [36].

Direct complexation was done by adding methanolic solution of acetylacetone to the solution of 2-aminopyridine and subsequent addition of Zinc-acetate (di-hydrated) salt (Figure-2.4)

Figure 2.4: Proposed structure of Zn complex

followed by the condensation for few hours by M. Jafari et al. The complex compound was then subjected to investigate antibacterial activity against four pathogenic bacteria. The selected species under test were Bacillus subtilis (Gram positive), Staphylococcus aureus (Gram-positive), Enterobacter cloacae (Gram-negative), and Escherichia coli (Gram-negative). From the values of Minimal Inhibitory Concentrations (MIC) and Mnimum Inhibitory Concentrations (MBC) it has been concluded that synthesized complex has remarkable activity against all the bacteria in concentration range over 150-325µg ml^-1 at 37^◦c [37].

The Schiff base ligand, Tris[(4-hydroxy-pentenylidene-2imino)-ethyl] amine was prepared from acetylacetone and tris(2-aminoethyl) amine and Fe (III), Ni (II), and Mn (III) complexes were prepared by Roya Ranjineh Khojasteh and Sara Jalali Matin. Antibacterial activity of the derived complexes were evaluated against both of the Gram-negative bacteria; Escherichia coli, Pseudomonas aeruginosa and Gram-positive bacteria; Staphylococcus aureus, Bacillus cereu. The outcome of these studies have indicated that metal complexes were more potent as antibacterial agent as compared to the ligand. Even the complexes have comparable potentiality against all the bacteria with respect to standards used; Choloramphenicol, Ampicilin [38].

Schiff base ligand was synthesized from thiosemicarbazide and 2,6-diace- tylpyridine and then complexation of ligand with Pd (II), Pt (II), Rh (III) and Ir (III) metal salts was performed by Monika Tyagi, Sulekh Chandra. Antifungal and antibacterial activity of all the synthesized compounds, ligand and metal salts were tested, for the sake of comparative studies against some common bacteria; Staphyloccocus aureus Escherichia coli and fungi; Aspergillus niger Aspergillus fumigates Fusarium odum. Upon conclusion it has been suggested that metal complexes has higher activity than free ligand and metal salts and it also indicated that pd complex show better activity as compared to the other complexes. Advancement in activity was explained on the basis of Chelation Theory. Polarity of the central metal atom reduced through the interaction with donor atoms upon chelation. Subsequently enhanced lipophilic nature of corresponding metal atoms that facilitate to penetrate through the lipid layer of the microbes cell membrane [39].

Schiff base ligands derived from acetylacetone and aromatic aldehydes (benzaldehyde), cinnamaldehyde and transition metal complexes of ligands with Cu (II), Ni (II), Co (II) chloride salts have been synthesized with the aid of condensation in ethanol by S. Sumathi et. al.. Biological activities of all the complexes, ligands and salts were tested against bacteria and fungus (P. aeruginosa, S. aureus, E. coli, C. albicans) using Amikacin and ketoconazole as reference standard. Result of these studies have indicated that derived complexes show more activity in opposition to fungus and bacteria than the ligands. Chelation was said to be the reason of enhance activity of complexes. Neither of the complexes nor ligands were active than the used standard drugs [40].

A Schiff base were prepared from acetyl acetone and leucine then Complex of the ligand was derived from condensing with cobalt (II) chloride salt [41]. Antifungal activity was evaluated for both of the ligand and complex against, Candida albicanand, Sacchromyces cerevisiae. It has been suggested that Co complex was potentially active against the organisms used both the moderate and excess concentrations. On the contrary, ligand show no resistant behavior towards the selected pathogens.

A new Schiff base ligand (Figure-2.5) was derived from naphthofuran-2-carbohydrazide and diacetylmonoxime (derivative of acetylacetone). Complexation of the synthesized ligand was carried out by refluxing chloride containing salts of Co (II), Ni (II), Cu (II), Cd (II), and Hg (II) in ethanol by R. B. Sumathi and M. B. Halli. Investigation of biological activites of the complexes and the ligand were performed against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa bacteri and Aspergillus niger, Aspergillus flavus, Cladosporium oxysporum, and Candida albicansfungi. From the studies it was implied that the complexes show better biological activity in contrast to the ligand. Specifically, complex of Cd (II), and Hg (II) have shown maximum resistant to the subjected pathogens as compared to the remaining complexes, since lipophilic nature of the complexes enhanced abruptly due to chelation [42].

Figure 2.6: Proposed structure of Cu, Cd and Hg complexes

Ethanolic solution of cobalt (II), nickel (II) hydrated salts have been added to the mixture of acetylacetone and 2-aminopyridine and the reaction mixture was refluxed to obtain complexes by Mehdi salehi et al. The complexes were subjected to investigate antimicrobial activity against pathogenic bacteria; Staphylococcus aureus, Bacillus subtilis [Gram-positive], Escherichia coli, Enterobacter cloacae [Gram-negative]. Choloramphenicol and kanamycin were also applied as standard drugs. From the experimental values of minimum inhibitory concentrations, a conclusion has been drawn that complexes show admissible antibacterial activity against the gram negative bacteria than gram positive and it also been illustrated Co (II) complex was good antibacterial agent rather than Ni (II) complex [43].

Condensation of acetylacetone (10 mmol) and 4‐hydroxy‐3‐methoxybenzaldehyde (10 mmol) in ethanol (40 ml) in the presence of piperidine (0.05 ml) was carried out to obtain 3‐(4‐hydroxy‐3‐methoxybenzyl) pentane‐2,4‐dione. Knoevenagel condensate Schiff base ligand was derived by the further condensation of 3‐(4‐hydroxy‐3‐methoxybenzyl) pentane‐2,4‐dione and 4- aminoantipyrine in ethanol by Rajakkani Paulpandiyan et al.. Chloride salts of Co (II), Ni (II), Cu (II) and Zn (II) were used for complex formation with the previously synthesized ligand. Biological efficiency of the complexes and ligand have been evaluated against bacteria and fungus. Two Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis) three Gramnegative bacteria (Escherichia coli, Klebsiella pneumoniae and Salmonella typhi) and five fungi (Aspergillus niger, Fusarium solani, Curvularia lunata, Rhizoctonia bataticola and Candida albicans) were taken to undertake that test. From the studies of Minimum Inhibitory Concentration values it have been elucidated that complexes show potent activity than the free ligand. Furthermore, it assumed improve activity of complexes due to the chelation property [44].

The ligand was obtained from Benzidine (0.0051 moles) and acetylacetone (0.0102 moles) requird amount of ethanol through refluxation. Etanolic solution of metal; Cr (III), Fe (III), Co (II), Ni (II), Cu (II) and Zn (II) chloride salts were fefluxed with the ligand (1:1 or 1:2 ratio) separately to synthesize complexes by Abdul hakim et al.. The authors mentioned that both the ligand and complexes had acceptable biological activities [45].

Oxovanadium (IV) complexes were synthesized from Schiff base ligands which were obtained from acetyl acetone and amino acids by Misbah ur Rehman et al. In vitro antibacterial activity of the complexes and ligands were studied against two Gram-negative (Escherichia coli, Salmonella typhi) and two Gram-positive (Bacillus subtilis, Staphylococcus aureus) bacterial species. In addition, Trichophyton longifusus, Candida albicans, Aspergillus flavus, and Candida glaberata species were used to study antifungal activity by disc diffusion method. Standard drug, chlorohenicol was also employed for activity comparison. Evaluated data have revealed that complexes have higher activity than ligands but lower than the standard drug used and potent activity of complexes were presumed upon chelation [46].

Cu (II), Ni (II) and Mn (II) complexes have been derived by the condensation of corresponding metal salts with Schiff base which was obtained from Phenylalanine and acetylacetone by Siraj, I. T. and Sadiq, I. A. The ligand along with its synthesized metal (II) complexes were tested for their antibacterial activity against Staphylococcus aureus (Gram-positive), Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Klebsiella pneumoniae (Gram-negative) bacterial strains and antifungal activity against Candida albicans, Fusarium solani and Aspergillus fumigatus with the variation of concentrations .Tentative inhibition zone(mm) of Schiff base and the metal complexes ascertained to have potential antibacterial and antifungal resistance property at high concentrations. Especially, Cu (II) complex has highest inhibition zone against Staphylococcus aureus and supposed to treat disease caused by it [47].

2.2 Anticancer property:

The ligand 2-hydroxy-N`-((Z)-3-(hydroxyimino)-4-oxopentan-2-ylidene) benzohydrazide (Figure-2.7) was derived from 2-Hydroxy benzohydrazide and diacetyl monoxime (a derivative of acetylacetonate) in ethanol. A series of noble metal complexes (Figure-2.8)

Figure 2.7: (E)-2-Hydroxy-N-((Z)-3(hydroxyimino)-4-oxopentan-2-ylidene) benzohydrazide Ligand

Figure 2.8: Proposed structure of the complexes

were synthesized by the condensation of copper (II), Nickel, cobalt (II), manganese (II), zinc (II) and cadmium (II), Mercury (II), and iron (II) acetate salts with H₂L by Abdou Saad El-Tabl et al. Cytotoxicity of ligand and the complexes were tested against human liver HepG₂cancer cells and applied concentration range were 0.1–100𝜇g/L .IC₅₀value was evaluated for each complexes as well as ligand in addition, Sorafenib (Nexavar) standard drug was also employed for comparative studies. From IC₅₀values it was confirmed that ligand and its complexes (IC₅₀= 2.24–6.49𝜇M) have significant anticancer activity as compared to standard drug used. Beside this, Cu-complex has lowest IC₅₀(2.24 𝜇M) value which attributed to its highest anticancer property. Appreciable cytotoxic effect of the complexes was illustrated with the aid of Tweedy’s chelation theory [48].

Antitumor activities of Organotin (IV) Complexes were examined against (ID₅₀ values measured in ng ml^-1) against MCF-7 and EVSA-T (two breast cancers), WiDr (a colon cancer), IGROV (an ovarian cancer), M₁₉ MEL (a melanoma), A₄₉₈(a renal cancer) and H₂₂₆ (a lung cancer) of Bu₂SnL-1(I), Bu₂SnL-2(I), Bu₂SnL-6(II), Ph₂SnL-1(I) and Ph₂SnL-2(I). ID₅₀ values of clinically used compounds (Carboplatin, Cisplatin, 5-Fluorouracil, Methotrexate, Doxorubicin) and of tri-n-butyltin pentaﬂuorocinnamate were also evaluated. Evaluated ID₅₀values have showed that all the complexes have higher activity against all the cell lines than of reference compounds, carboplatin and cisplatin. Moreover, Bu₂SnL-1(I), Bu₂SnL-2(I), Bu₂SnL-6(II) were considerably more active as compared to 5-ﬂuorouracil but less active than methotrexate and doxorubicin. In addition, dibutyltin derivatives of the Schiff bases were found to be more effective anticancer agent than of which derived from diphenyltin.

In vitro cytotoxic activity of the synthesized compounds (Figure-2.9) were tested against a couple of cancer cell lines, MCF‐7 and HeLa, and a couple of non‐cancerous cell lines, NHDF and HEK, using MTT assay, cisplatin was used as standard (positive control). The cell lines were subjected to the synthesized compounds for 48 h at a range of concentrations (0–100 μM). IC₅₀values (concentration of drug required to inhibit growth of 50% of cancer cells) were calculated and results have revealed that Complexes (1–4) show acceptable cytotoxic activity against the experimental cell lines .IC₅₀values of the complexes have been confirmed that, complex(1) was potentially stronger to inhibit the proliferation of HeLa and MCF‐7 cells than cisplatin under same experimental conditions. Evaluated IC₅₀values for complex1 were found to be 18 and16 μM whereas 22 μM and 26 μM for cisplatin that clearly indicating the anticancer activity of complex (1) is better than that of cisplatin. Specifically, results of in vitro cytotoxic activity indicate that the IC₅₀values of the synthesized complexes against non‐cancerous human cell lines (NHDF and HEK) are found to be above 72 μM which indicates that complexes (1–4) are very specific towards cancer cell lines only.

The catalytic oxidation of cholesteryl acetate (10 mmol) was performed in presence of (1 mmol) NHPI, 70 ml acetone, 10ml of 1,4-dioxane with the variation of catalyst amount. It has been find that Co-catalyst is more efficient than the Cu-catalyst. From the experimental data it has been indicated that only 2% of [Co(acac–py)₂] [Cl₂] as calalyst give highest yield of 7-ketocholesteryl acetate (Oxidised product of cholesteryl acetate) under mild condition. Moreover, Co catalyst was reproducible by water wash method and regenerated catalyst can be used at least four times [49].

Chemically efficient copper amino acid Schiff Base Catalyst was prepared by Meizhu Rong et al. The Cu-complex was used as catalyst for the oxidation of alcohols. Catalysis of benzyl alcohol (2 mmol), have been conducted by adding cataylst (0.02 mmol) and [bmim]BF4 (1mL) in a microreactor under constant stirring for short time, followed by the addition of tert-butylhydroperoxide (10 mmol) and stirred for few seconds. Yield of the product (benzoic acid) was 88%. Apart from benzyl alcohol, the catalyst was also applied to the other alcohols and yield of product were more than 80%. It has been identified that, this catalyst can be recycled and reused for further reactions and able to show significant catalytic activity [50]. Transition metals (Vanadium (III), chromium (III), manganese (II), manganese (III), iron (III), cobalt (II), nickel (II), copper (II), zinc (II), manganese (II) hexafluoro) complexes of Acetylacetonate were bought from Sigma-Aldrich but Iron (III) hexafluoroacetylacetonate was taken from Tokyo Kasei Kogyo Co. by atsushi sudo et al.. The complexes were then employed to the ring-opening polymerization of benzoxazine as catalyst. The result of these studies have indicated that acetylacetonate complexes of manganese, iron, and cobalt have comparable or slightly higher activity exhibited by p-toluenesulfonic acid. The replacement of acac ligand by hexafluoroacetylacetonato (F₆-acac) ligand, markedly enhance the activity of manganese and iron complexes as it possessed through augmented Lewis acidity. The ability to tolerate moisture, high activity, and thermal stability of the formed poly(benzoxazine) were the reason for selecting F₆-acac complex of manganese as optimum catalyst [51].

Supported transition metal oxide catalysts (Mo, Cu, V) were obtained by the molecular designed dispersion method by M. Baltes et al. The corresponding transition metal acetylacetonate complexes were interacted with silica or alumina, and converted into the supported metal oxide thermally. The deposition of these acetylacetonate complexes takes place in two ways, either liquid phase or gas phase. Between the two metods, gas phase pathway plays a pivotal role for the generation of new catalysts as it eliminate the solvent effect. Moreover the rate of deposition depends on the stability, geometry of the precursor complexes along with the supported properties and the synthesis method. The deposition can be controlled by maintaining temperature and the concentrations of supported materials. Therefore, regulation of the reaction parameters, the molecular designed dispersion process is a very promising route of designing a catalyst system that acted as robust catalyst [52].

To the suspended solution of amino functionalized silica gel (SiO₂-NH₂) (3.0g) a mixture of acetyl acetone (10 mmol) and copper acetate (5 mmol) in ethanol (30ml) was added and the resultant mixture was allowd to refluxed for 5 h. The solid was isolated by the filtration followed by washing with hot ethanol in order to dispel the excess copper acetate .The separated solid was kept under vacuum( at 60°C) to dry and marked as SiO₂-NH₂-Cu(II) by G. ANBARASU et al..The Efficiency of synthesized silica functionalized Cu(II) Schiff base complex as a catalyst was assessed for the oxidative condensation reaction of benzyl alcohol in presence of different aromatic/aliphatic amine. An attempt has been taken to find the maximum yield of the product(imines compounds) by the variation of catalyst amount like 10 mg, 20mg, 30mg, 40mg, 50mg and 100mg. The results suggested that rate of conversion benzyl alcohol with amine were found to be maximum (94%) while the amount of catalyst was 50mg. It was also pointed that increasing amount of catalyst also increases the product but more than optimum (50mg) amount failed to enhance the rate of reaction in toluene. The activity of that catalyst was comparable or slightly more than the reported catalysts, even it was found to be reusable with negligible loss of activity [53].

The novel acid-base hybrid catalyst, RNH₂-M(acac)₂complex were produced by S. Tanaka and K. Adachi by the slow addition of M(acac)₂ dissolved in chloroform to a solution of n-alkylamine that was previously dissolved in chloroform and stirred for 2h. The water-crosslinking reactions of EPR-g-MTMS was carried out in the presence of RNH2-M(acac)₂ complex as catalyst, the same reaction was performed in the absence of catalyst at three different temperatures (30^◦, 50^◦, and 80^◦C). The results have indicated that catalytic activity of RNH₂-M(acac)₂was higher than the M(acac)₂and n-alkylamine. Enhanced activity of RNH₂-M(acac)₂catalyst was explained by the axial co-ordination of n-alkylamine to M(acac)₂[54].

Schiff base ligand bis(2-hydroxyanil) acetylacetone (H₂haacac) was derived from 2-aminophenol and acetylacetone in ethanol and complexes of general formula, [M(haacac)] of a tetradentate Schiff base ligand H₂haacac with transition metal Mn(II), Co(II), Ni(II) and Cu(II) were synthesized .Therefore alumina supported metal complexes were subjected to the oxidation of cyclohexene with tert-butylhydroperoxide(TBHP) as catalyst. 2-cyclohexene-1-ol (–OH), 2-cyclohexene-1-one (C=O) and 2-cyclohexene-1-(tert-butylperoxy) (–OOtBu) were the main oxidized products of this catalyst based reaction. Presence of non-coordinating solvent in reaction medium gave maximum yield of product as compared to the coordinating solvent, beside this 70^◦C temperature was pointed as optimum temperature. From comparative studies, a conclusion has been made that alumina supported Mn (II) complex show higher catalytic activity than others. Moreover, end of reaction catalysts didn’t change their color and recycled for the next reactions [55].

To evaluate the catalytic activity, synthesis of the complexes of ruthenium(ll), [RuBr(acac)L₂]₂ (L = PPh₃, AsPh₃ py; L₂= bipy or phen) and M₂ [RuBr₃ (acac)] (M = Me₄N, Cs or Rb) were narrated by BIPUL C. PAUL et al.. Oxidation of PPh₃, and AsPh₃ aid of molecular oxygen was carried out in presence of synthesized complexes as catalyst. A co-ordinating solvent acetonitrile was used in the reaction and the resultant product were OPPh₃ and OAsPh₃.The conversion of PPh₃ to OPPh₃ was 65% whereas OAsPh₃was only 25%. It assumed that acetonitrile influence to cleaves the bromo bridges of the dimer which in turn forms the monomer [RuBr(acac)L₂ (CH₃CN)]. Catalytic species assembled in the solution due to further loses of coordinated ligands [56].

Mn(acac)₂-ethylenediamine catalysts was simply derived from Mn(acac)₂ and N,N’-diethylethylene-diamine by Soichiro Murakami et al. Oxidative coupling polymerization (OCP) of p-alkoxyphenols with Mn (acac)2-ethylenediamine catalysts was carried out in dichloromethane (CH₂Cl₂), under mild condition and O₂existing atmosphere.The polymer obtained was essentially composed with m-phenylene backbone, on the other hand polymerization occurred by Mn(acac)₂ afforded polymer consist of oxyphenylene backbone. The process of polymerization was accompanied by the one-electron oxidation to produce Mn (III) from Mn (II). A series of polymerization reactions were performed by changing amines along-with temperature and keeping Mn(acac)₂ unaltered. Finding of reactions indicated that 57% yield of product with maximum unit ratio of CC/CO = 95/5 has obtained in case of synthesized catalyst which was described above. High effectiveness of that catalyst was governed by regiocontrol ability [57].

Bidentade ligands APOH=(4-anilino-3-penten-2-one), DPOH= 4-[2,6-dimethylanilino]-3penten-2-one, and MTPOH= 4-[2-(methylthio)anilino]-3-penten-2-one were derived from acetylacetone and suitable amine by Sachse et al. according to modified method than the literature (figure ).Substitution reactions of ligands with rhenium(V) oxo precursors [ReOCl₃(PPh₃)₂] or [NBu₄][ReOCl₄] gave rhenium(V) oxo complexes(Figure-3.3).

Figure 3.3: Synthesis route of Re(V) Oxo complexes (Catalyst)

Only [ReO (DPO)Cl₂(PPh₃)] compound was potent to the catalytic activity. Oxidation of cis-cyclooctene was performed in presence of synthesized catalyst with tert-butylhydroperoxide (TBHP) in non-coordinating solvent (Figure-3.4). This catalytic reaction was easily identifiable, hence epoxide was only detectable product. In that case, result also supports higher activity of acetylacetone based catalyst than salicylaldehyde-based catalysts [58].

Figure 3.4: Catalytic Epoxidation of Cis-cycloctene

A simple protocol using cationic acetylacetonate palladium complexes with mono-/bidentate phosphine ligands activated with BF₃·OEt₂ as in situ-formed catalyst for polymerization of endo/exo mixture of 5-methoxycarbonylnorbornene (activity up to 1.1·104 g mol⁻¹ h⁻¹) or 5-phenylnorbornene (7.2·105 g mol−¹h⁻¹) and norbornene (3.3·108 g mol⁻¹ h⁻¹) have been developed. It was observed nature of the ligands strongly inﬂuence the catalytic activity. The catalyst system Pd (II)/BF3·OEt2 was also active for the copolymerization of norbornene with 5-methoxycarbonylnorbornene. DFT calculations of isomers upon single insertion of 5-methoxycarbonylnorbornene into Pd-H bond and NMR/FTIR studies for pre-catalyst activation mechanism was also performed. The easily available two component catalyst systems [Pd(acac) (PR₃)₂]BF₄/nBF₃·OEt₂ was highly useful for the addition (co-)polymerization of norbornene and its important derivatives 5-methoxycarbonylnorbornene and 5-phenylnorbornene [59]. Nanocrystalline iron, chromium, and manganese oxide were derived by adopting most a multipurpose, xpedient and harmless solvothermal method Amanda L.Willis et al..This method have employed the reactions of metal [Fe(III),Mn(III) and Cr(III)] acetylacetonate precursors with the variation of oxygen containing solvents and appropriate reaction conditions (heat andtemperature). 2-Acetylpyridine (AP) bp 188^◦C, p-anisaldehyde (PA) bp 250^◦C, γ-butyrolactone (BL) bp 204^◦C, Ethylene carbonte (EC) bp 250^◦C, 1-formylpiperidine (FP) bp 220^◦C have been used as capping ligands/solvents that affected the solubility of nanocrytalline metal oxides in both the polar and nonpolar solvent(Figure-3.5).

Figure 3.5: Synthesis of water soluble iron oxide nano particles by heating Fe(acac)₃ in 1-foemylpiperidine solvent.

Acetylacetonate precursors have been found to be advantageous for being environmental friendly, inexpensive and ease of preparation [60]. Recyclable catalyst have been designed at molecular level by anchoring of a metal complex catalyst onto a solid support by means of covalent bond. Neverthless/however performance of the derived solid catalyst depends largely on the stability and flexibility of the linker between metal complex and solid support. A ring-opening reaction of 2-butoxy-3,4-dihydropyrans was carried out in presence of a nucleophile to produce 2-alkylated 1,3-dicarbonyl compounds. In particular, when the nucleophile were mercaptans, progress of the reaction took place smoothly and featured by good atom-economy (environmental friendly), admissible yield of product at mild conditions have been obtained by Bingbing Lai et al. With the aid of this reaction, they have used,2-butoxy-3,4-dihydropyrans as dual anchoring reagents and ligand donors to modify a ready-made SH-functionalized HMS. This opened an easy way to construct a robust and flexible linker for anchoring a metal acetylacetonate complex catalyst onto HMS support. Therefore, obtained HMS was be used to immobilize Cu(acac)₂, Zn(acac)₂ and Ru(acac)₃ complexes. The obtained solid catalysts were fully characterized by many physicochemical methods. These catalysts were accompanied by trustworthy activity in various organic reactions as compared to their homogeneous counterparts. Moreover, catalysts were asserted to be perfectly robust and recyclable for several times with prominent activity [61].

CONCLUSION:

The transition metal complexes derived from acetylacetone containing schiff base ligands were exceptionally stable. Studies of bacterial and fungal screening have remarked that ligands and complexes were potent against bacterial and fungal strains. Few Cu (II) complexes have been classified as anticancer agent, in some cases it show higher activity as compared to the clinically used therapeutic agents with excellent DNA binding property. Some of the complexes were active catalyst for polymerization and oxidation of organic species. After studying all sorts of activities, In this review, it has been concluded that acetylacetonate and acetylacetonate derived Schiff base containing metal complex synthesis is an active line of research which has contributed to creating antimicrobial as well as catalytic agents and this review will provide ample references for researchers to further their research in this area and will be profitable to students as well.

COMPETING INTERESTS:

Authors have no competing interests.

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Received on 27.05.2020 Modified on 25.06.2020

Asian J. Research Chem. 2020; 13(5):395-406.

DOI: 10.5958/0974-4150.2020.00073.5