**2.6 Ligand exchange reaction**

It is very challenging to synthesize molecules such as dioxomolybdenum(VI) complexes, for which there are different techniques. The most preferred method is the ligand exchange method. Below is an example of a common response [11].

$$\text{MoO}\_2(\text{acac})\_2 + \text{SalenH}\_2 \to \text{MoO}\_2(\text{Salen}) + 2\text{acacH}\_2$$

Where: acac = acetylacetone.

**Figure 1.** *Synthesis of SB from a secondary amine.*

#### **2.7 Template synthesis**

A template reaction in coordination chemistry is any of a group of ligand-based reactions that take place between two or more nearby coordination sites on a metal center. When there is no metal ion present, the same organic reactants result in different end products. Although the coordination modifies the electronic properties of ligands (acidity, electrophilicity, etc.), the template effects highlight the preorganization provided by the coordination sphere. In a general sense, transition metalbased catalysis can be viewed as template reactions: Reactants coordinate to adjacent sites on the metal ion and, owing to their adjacency, the two reactants interconnect (insert or couple) either directly or *via* the action of another reagent. In the area of homogeneous catalysis, the cyclo-oligomerization of acetylene to cyclooctatetraene at a nickel(II) center reflects the templating effect of the nickel, where it is supposed that four acetylene molecules occupy four sites around the metal and react simultaneously to give the product. The development of these catalytic reactions was influenced by these crude mechanistic hypotheses. For instance, only three acetylene molecules could bind if a competing ligand, such as triphenylphosphine, was added to occupy one coordination site. These three molecules then combine to form benzene.

This process involves the interaction of an aldehyde, an amine, and a metal compound in a single step to create complexes without the need to isolate Schiff bases [12, 13]. Metal ions are serving as a catalyst for these reactions. Rotaxanes, helicates, macro cycles, and catenanes are just a few examples of assemblies with unique topologies that have been produced using template synthesis [14]. The information needed to arrange a group of building blocks so that they can be connected in a certain way is therefore said to be contained in a templating agent. Thermodynamic and kinetic processes are the two different categories of these templates. The template binds to one of the reactants in the first case, shifting the equilibrium in favor of the product formation. With regard to kinetic processes, the templates work under conditions that are irreversible, stabilizing each transition state and causing the formation of the intended product. The template is tightly coupled to the end species in many kinetically regulated processes. In these situations, it serves as both a thermodynamic template and a kinetic template. Gimeno et al. defined a template can be class that arranges a grouping of molecular construction pieces through noncovalent interactions that favor the creation of a particular complex in their review (**Figure 2**) [15].

#### **2.8 Rearrangement of heterocycles (thiazole and oxazoles)**

When an *o*-mercapto amine or o-amino, and o-hydroxy are directly combined with a carbonyl molecule to generate a SB, ring closure and the production of a heterocyclic compound are frequently the unintended side reactions [16]. Hugo Schiff first converted SB into its metal chelate in 1869 [17]. According to reports, the benzothiazoline and benzoxazole rings can open in particular situations when metal ions are present, and this ring rearrangement creates the necessary metal chelates for the SBs. This type of ring opening complexation process is shown in **Figure 3**.

### **3. Chemistry of Schiff bases**

Hugo Schiff, a Nobel Prize laureate, first identified SBs as a condensation outcome of carbonyl compounds and primary amines [18]. SB is a structural counterpart of an –

**Figure 2.** *Bridged dinuclear copper (II) SB complex using template method.*

**Figure 3.** *2-(2-hydroxyphenyl) benzothiazoline.*

CHO or –C=O where C=O has been exchanged out for an imine or an azomethine group (**Figure 4**) [3, 19].

A chemical molecule known as a Schiff Base, or SB, contains a C-N double bond, where the N is linked to an aryl group or an alkyl (R) but, not to an H-atom. A molecule containing azomethine linkage is the same as the SB. Hugo Schiff was honored by having his name attached to several compounds, which generally have the following structure:

The SB is an imine since R stands for an alkyl or phenyl group, making it a stable compound. Even the imine N and other group, typically connected with aldehyde, this type of ligands, can coordinate metal ions. SBs are still created by chemists, and today's "privileged ligands" are active, well-designed Schiff base ligands [20]. The bridging SBs possess below given structure, where it consists of several functional groups that can be altered depending on the situation (**Figure 5**).

**Figure 5.** *Bridged SB.*

Where R' here might be a H or R group, R" is a phenyl or substituted phenyl, and X is alkyl or aryl group. In fact, SBs can influence the activity of metals in a broad range of beneficial reactions in catalysis by stabilizing a wide variety of metals in a variety of oxidation states [21]. The oxygen atoms in SBs are often donated by NO or N2O2, although they can be substituted by S, N, or Se atoms. **Figure 6** shows the synthesis of SB by condensation reaction.

R, here, might be either aryl or an alkyl group. Aryl SBs are significantly more stable and easier to synthesize than their alkyl counterparts, which are more prone to instability. Aliphatic aldehyde SBs are comparatively not stable and easily undergo polymerization [22]. Aldehydes or ketones can be converted into SBs in a reversible process that often occurs when the substance is heated or when an acid or a base catalyzes the reaction (**Figure 7**).

In most cases, the product is separated from the reaction, or when the water formed is removed, or sometimes in both cases. Aqueous acid or base has the ability to hydrolyze several Schiff bases back to their respective aldehydes, ketones, and amines. Nucleophilic addition to the carbonyl group is a common theme in the synthetic route of Schiff base formation. The amine serves as a nucleophile during this

**Figure 6.**

*Synthesis of SB by condensation reaction.*

#### **Figure 7.**

*Reversible reaction of SB formed by the interaction of aldehydes or ketones.*

**Figure 8.** *Mechanism of formation SB.*

instance. In the first step of the procedure, the amine reacts with the aldehyde or ketone to produce an unstable addition substance known as carbinolamine. Either an acid- or a base-catalyzed pathway results in the carbinolamine losing water. This carbinolamine undergoes acid-catalyzed dehydration since it is an alcohol (**Figure 8**).

Usually, the rate-determining step in the creation of a SB is dehydration of the carbinolamine, which is why acids are used to catalyze the reaction. Yet because amines are basic chemicals, the acid concentration should not be exceeded. Equilibrium shifts to the left, and carbinolamine production is prevented if the amine is protonated and turns non-neutral. As a result, it is ideal to synthesize numerous Schiff bases at a pH that is a little acidic. The base also acts as a catalyst for the dehydration of carbinolamines. It goes through an anionic intermediate in two phases. In reality, the SB creation is a series of two different kinds of reactions, namely addition and elimination [23].

### **4. SB complexes in catalysis**

Excellent catalytic activity is displayed by several SBCs in diverse reactions and in the presence of moisture. Numerous studies on their use in homogeneous and heterogeneous catalysis have been published during the past few years. The high heat and moisture stabilities of many Schiff base complexes proved helpful for their application as catalysts in high-temperature processes. Due to the fact that complexation often causes an increase in activity, knowledge of the characteristics of both ligands and metals can help in the synthesis of substances that have high activity [14].

SBs were treated as crucial ligands in coordination chemistry for a long time [24, 25]. SBs are an essential type of ligands in coordination chemistry [26–28]. Owing to their relatively straightforward synthesis and diverse structural makeup, SBs and

their metal complexes were extensively studied because of their extraordinary properties and uses in variety of fields. These compounds are revealed to be auspicious for the synthetic and structural research field [1, 29, 30].

From the finding of chiral Mg (III) salen SB catalysts in the asymmetric epoxidation of unfunctionalized olefins in the 1990s, the tetradentate SB, salen-type ligand, and their complexes have attracted significant attention [31]. Due to their potential application as catalysts in a variety of C-C and C-N bond formation events, such as cyclopropanations, aziridination, asymmetric cycloaddition reactions, and A3-coupling, among others, Salen-Schiff base transition MCs have been well studied (**Figure 9** [32, 33]. For medicinal chemists, the design of the C-N bonds of aryl compounds is extremely crucial. Tetrazoles are a significant group of heterocycles among the many heterocycles that have been reported. In coordination chemistry, tetrazoles have been utilized as ligands, [34] stabilizers in the photographic industry, [35] linkers to covalently bind synthetic groups to biopolymers in a specific manner, etc. [36]. The A3 -coupling reaction is an appealing illustration of a multi-component reaction [37]. (**Figure 10**) [38]. Agrahari and coworkers carried out an A<sup>3</sup> -coupling reaction with less use of catalyst, and the catalyst was reclaimed for four successive cycles in the reactions [39].

The primary method for producing biaryls is the Suzuki-Miyaura cross-coupling reaction. This reaction is an effective technique for the production of medicines due to the properties and convenient accessibility of organoboron reagents [40]. Palladium is one of the transition metals that are most frequently employed in both industry and academia to produce C-N, C-S, and C-C bonds because it is a

**Figure 9.** *Metal salen-type complexes.*

#### **Figure 10.**

*4-bromobenzonitrile with phenylboranic acid.*

catalytically active metal [41]. In this context, during the past few decades, significant attempts have been made to synthesize potential substitute catalysts for crosscoupling reactions [42]. Transition metals in the first row are a particularly promising class of molecules that have the potential to be more useful in the field of catalysis than other transition MCs [43]. This work deals with the less harmful alternative to the commonly utilized palladium-phosphine ligand complexes for initiating Suzuki reactions: SB-Cobalt complexes. This work describes the synthesis of OON- and ONN-SBLs and their Co complexes. The created compounds were evaluated as Suzuki coupling reaction catalysts. This work utilized only 0.1 mM catalyst for the reaction [44].

**Figure 11.**

*Scheme 1(a–c) synthetic method for the preparation of Schiff base complex of BCNPOH and metal oxides.*

**Figure 12.**

*Scheme3: C-C coupling reaction of phenylboronic acid and iodobenzene.*

**Figure 13.**

*C-C coupling reaction of phenylboronic acid and 2, 6-dibromopyridine.*

SBL, BCNPOH, and metal salts (Cu, Co, Ni, Fe, and Cr) were individually dissolved in ethanol and followed by mixing both the solutions and reflux for 5 h at 70°C. The obtained precipitate was filtered and dried. CuL, CoL, NiL (**Figure 10**, Scheme 1b), FeL, and CrL (**Figure 11**, Scheme 1c) produced SB complexes that were recrystallized in ethanol [45].

The synthesized complexes were implemented for the C–C coupling reaction of Phenylboronic Acid and Iodobenzene and Phenylboronic Acid and 2,6- Dibromopyridine.

The coupling reaction between iodobenzene and phenylboronic acid was conducted (**Figure 12**). The reaction was completed in 95:5 DMF:water mixture under an inert nitrogen environment.

The coupling reaction between 2,6-dibromopyridine and phenylboronic acid was assessed at 110°C for 24 hours. (**Figure 13**). The reaction was taken to react in 5 mL of 95:5 DMF:water combination under an inert nitrogen environment with the limiting reagent 2,6-dibromopyridine and a molar ratio of the halide to the boronic acid of 1:2.4. The amount of catalyst was always 25 mg, and the molar ratio of the base (K2CO3) to the halide was 1:2 [45].

### **5. Synthesis for the transfer hydrogenation of ketones**

Through the use of pre-catalyst Ru(II) (**Figure 14**), the catalytic transfer hydrogenations of ketones were investigated (0.001 mmol). In *i*-propanol, the base KOH (4.0 mmol) was dissolved (5 mL). This combination was then combined with 2.0 mmol of the substrate ketone, and it was refluxed in an oil bath at 80°C for 8 hours. After the reaction was finished, the liquid was cooled and filtered using alumina or silica gel, and then eluted using an hexane /ethyl acetate (4,1) mixture. Compound purity was evaluated using GCMS. All of the complexes (1a–d) were discovered to be efficient catalysts, offering conversion rates between 70 and 100%. The transfer hydrogenations of acetophenone derivatives were successfully accelerated by a variety of unique Ru(II) complexes that were successfully synthesized in the current work and contained pyridine group-based Schiff bases. With benzophenone as a model substrate, the efficiency of the catalysts in the transfer hydrogenations was evaluated (**Figure 15**) [46].

#### **Figure 15.**

*Hydrogenation of ketone using Ru(II).*

Reliable zinc complexes for bulk polymerization of lactide have been studied at 150°C under applicable commercial circumstances. The utilized anionic Schiff base ligands (**Figure 14**) may be produced aerobically and are extremely stable against air, moisture, and other lactide contaminants. As a result, these compounds incorporate both a strong anionic ligand and a nontoxic, active zinc core (**Figure 16**). These compounds are ideally suited for lactide polymerization under industrially relevant circumstances due to their simple aerobic synthesis, high thermal stability under nitrogen, and air [47].

Cu-SBCs based on particularly ordered mesoporous silica MCM-41 were synthesized by Niakan et al., to create a heterogeneous catalyst (**Figure 17**). The synthesized catalyst was implemented for coupling reactions of Ullmann type. The synthesized catalyst showed excellent activity for the N-arylation of amines with aryl iodides and bromides. Here, 0.8 mol% of catalyst was used [48].

Bunno and group synthesized metal-containing SB/ Sulfoxides that served as chiral ligands for asymmetric intramolecular allylic C-H amination processes that are

**Figure 16.** *SBLs HL1–HL4, used for the synthesis of four new zinc Schiff base complexes.*

catalyzed by Pd(II).They claimed that the use of metal-containing Schiff base ligands helped to tune the reaction conditions. In the reaction, internal and terminal alkenes were both utilized [49]. A novel Cu(II) SBC on graphene oxide, GO-SB-Cu was successfully synthesized through surface functionalization of the GO (**Figure 18**). Potential of the catalyst was tested as heterogeneous catalyst in one-pot three component click reactions for synthesis of 2H-indazoles and 1,4-disubstituted 1,2,3-triazoles (**Figure 19**).

A reaction was carried out with aniline and 2-bromobenzaldehyde in the presence of sodium azide. Different reactions were carried out to set the optimized conditions using catalyst loading, solvent selectivity, temperature, and time for catalytic study of GO-SB [50].

One more important catalytic conversion reaction is in oxidation of alcohols into carbonyl compounds. A cobalt (II)-SBC with triphenylphosphine was synthesized (**Figure 20**). The catalyst was used for oxidation reactions using different substrates and obtained good % of conversion of carbonyl compound [51]. Dileep et al. have done experiment on the oxidation of primary and secondary alcohols to respective carbonyl compounds *via* green catalytic approach. Here, [NiCl2(PPh3)2] was synthesized by the reaction between NiCl2.6H2O and triphenylphosphine in the presence of glacial acetic acid. Condensation reactions between 2-hydrazinopyridine and substituted salicylaldehyde in methanol yielded Schiff bases with 70–80%. This study examines the relationship between catalyst concentration and substrate. According to this study, 0.02 mmol of catalyst was enough to effectively convert benzyl alcohol to benzaldehyde [52]. Novel palladium complexes were synthesized and characterized by different analytical techniques (**Figure 21**). The complexes exhibit strong catalytic activity when N-methyl-morpholine-N-oxide is present as an oxidant for the oxidation of primary and secondary alcohols. A mechanism of catalytic conversion reaction is shown below (**Figure 22**) [53].

A novel Ru-SBC composed of Ph3P was synthesized by and characterized by various techniques. The synthesized complexes were implemented for the oxidation of alcohols in [EMIM]Cl ionic liquid-NaOCl system. Recycling of catalyst is an important factor in catalysis. Herein, recyclability of catalyst for the conversion of

**Figure 17.** *A plausible mechanism for the Cu-SB-MCM-41-catalyzed C-N bond formation reaction.*

**Figure 18.** *HRTEM images of GO-SB-Cu.*

**Figure 19.** *Synthesis of 2H-indazole.*

**Figure 20.** *Cobalt (II)-SBC with triphenylphosphine.*

benzylalcohol is carried till seven consecutive cycles, shown in **Figure 23**. Recyclability graph indicates that recycling of ionic liquid has small significant effect on the conversion of the product [54].

For the catalytic oxidation of primary and secondary alcohols with periodic acid (H5IO6) as the oxidant, novel copper complexes were created and put into use [55]. Palladium was used as a catalyst in the carbonylation of alcohols in ionic liquid (IL) media (1-ethyl-3-methylimidazolium hexafluorophosphate). The usage of Pd-based catalyst, where NaOCl is utilized as an oxidant, considerably improved the carbonylation of primary/secondary alcohols to aldehydes/ketones [56]. *In situ* strategy of immobilization of a Cu complex onto an ionic liquid support was focused in this work. Olefin and terpene epoxidation was carried out by the immobilization of a copper complex and 1-ethyl-3-methylimidazoliumhexafluorophosphate, along with H2O2 as the terminal oxidant is developed. This method brings a clean environment nature for catalytic epoxidations (**Figure 24**) [57].

A SB Pd complex was studied for the catalytic activity in ethyl-methyl imidazolium hexafluorophosphate [EMIM] PF6 ionic liquid. This work shows air stable system for Heck and Suzuki reactions. In the [EMIM] PF6-Water system, the palladiumcatalyzed coupling process demonstrated remarkable fidelity [58]. Copper complex

**Figure 21.** *Palladium SBC with triphenylphosphine.*

was studied for the catalytic application in Heck and Suzuki reactions (**Figure 25**). The reactions were conducted in [EMIM]PF6 ionic liquid-water mixture with 1:1 ratio, which was observed to be helpful during catalyst recycling and reusing [59]. These compounds demonstrated improved catalysis for the N-alkylation step required to produce benzazoles (**Figure 26**). The reaction progressed *via* a hydrogen transfer mechanism (**Figure 27**). It was observed that the reaction in EMIM [PF6]-Water [1] mixture as solvent bought a considerably better yield with in a less reaction time (**Figure 28**) [60].
