**2. Synthetic methods of Schiff bases**

Schiff base ligands, a class of molecules having imine groups, have grown in popularity due to their physiological and pharmacological properties. They are a fascinating class of chelating agents capable of coordinating metal ions in a complex, which is used to imitate biological processes. Many studies have been conducted on synthesizing Schiff bases [41–43]. Schiff bases have been prepared using conventional and green synthetic methods (**Figure 3**).

Heat is required in many condensation processes, and traditional reaction conditions often involve heating the reactants in a metal, oil, or sand bath for hours or even days. The conventional procedure involves refluxing or stirring different aldehydes or ketones with various types of primary amines. Green chemistry refers to the tools and procedures that provide considerable environmental and financial benefits over conventional synthetic approaches. It depicts that the current in green chemistry has triggered a new demand for organic synthesis in which distinct reaction environments must be located, reducing the usage of harmful organic solvents or toxic chemicals. Green approaches must improve selectivity, reduce reaction time, and simplify product isolation over conventional methods. Microwave-assisted synthesis of Schiff bases has been carried out without solvent or low-solvent conditions and reduces reaction time significantly, improves conversion, and sometimes increases selectivity. Since the development of solvent less microwave synthesis of Schiff bases, it has become the most well-known and simple technique for these reactions and is used in various applications. Many researchers reported using the microwave-assisted synthesis of various types of Schiff bases and their derivatives.

The grindstone technique reaction creates local heat by grinding substrate crystals and reagent with a mortar and pestle. Grinding starts reactions by transmitting a

## *Schiff Bases and Their Metal Complexes: Synthesis, Structural Characteristics and Applications DOI: http://dx.doi.org/10.5772/intechopen.108396*

relatively small quantity of energy through friction. In some circumstances, a mixture and reagents form a glassy substance. Such reactions are simple to handle, eliminate pollutants, are relatively cheaper to operate, and may be considered more economical and environmentally friendly in chemistry [18]. Because molecules in a crystal are organized tightly and regularly, solid-state reactions are more efficient and selective than solution reactions [19]. The synthesis of amino acid Schiff bases (3) in water by the reaction of variously substituted aromatic aldehydes/heterocyclic aldehydes (2) and dl -alanine amino acid (1) stirring at room temperature (method A) using grindstone chemistry (method B), microwave irradiation (method C), and conventional heating (method D). Studies comparing the times required to synthesize four distinct Schiff bases under four different conditions found that while method B (grindstone) had a better product yield, it also took significantly longer than procedures A, C, and D., i.e., Product yields ranged from 72 to 78% after being subjected to grinding for 30–35 minutes followed by leaving the reaction mixture overnight (8 h). Product yields of 69–73% were achieved in 40–45 minutes when the reactants were stirred in water at room temperature (15–20°C). Microwave irradiation (method C) and ordinary heating (method D) were also used to synthesize compounds. In 5–6 minutes, yields of 70–72% were achieved under microwave irradiation, which is much quicker than grinding (method B). The highest yield and shortest reaction time were both achieved by using Method C (**Figure 4**).

Sonication is the use of high power to excite particles for various purposes. Ultrasonics with frequencies greater than 20 kHz is normally employed in a process known as ultrasonication [45]. In the laboratory, it is typically used with an ultrasonic bath or probe; this apparatus is known as a sonicator. A new approach for

#### **Figure 4.** *Synthesis of Schiff bases 3a–3f with different methods and comparisons [44].*

synthesizing Schiff bases under catalyst-free ultrasonic irradiation conditions has been discovered, yielding 92% compared to the current method's 84% yield [46]. They discovered an efficient and environmentally friendly method for Schiff base synthesis in an aqueous solution using ultrasonic irradiation conditions and thus no catalyst. Several research publications revealed how different green synthesis techniques could cause a specific condensation process to occur preferentially. When opposed to solution-based synthesis, mechanochemical synthesis has the advantage of ease of set-up and high yields [47]. Most Schiff bases have reported more excellent ligation with metal ions because of a lone pair of electrons in these compounds. The number of transition and other metal ions complexes were synthesized by using novel Schiff base ligands [17].
