It's been a long time; heterogeneous catalysts have been known and used as an effective and environmentally friendly agent for organic transformations and to prevent the production of by-products[1–6]. These catalysts have several advantages including high selectivity, high turnover numbers (TON), and effortless optimization of catalytic activity, for example, by simply tuning ligand and metals in the case of metal complex catalyzed reactions[7, 8]. Various substrates are used to stabilize catalytic factors, which is one of the most important substrates is magnetite (Fe3O4)[5, 9]. Magnetite is an ideal oxide substrate that has a very active surface to absorb or stabilize metals and ligands and on the other hand, it can be easily separated and recyclable by applying external magnetic fields from the reaction medium[10–15]. Although the Fe3O4 magnetic nanoparticles (MNPs) are attracted to their unique properties, such as low price, broad availability, high surface area, Increased reaction rate by local heat through induction, thermal stability, low toxicity, easy separation of the reaction mixture by the application of an external magnetic field, a good potential for consolidation of different groups and excellent recycling capability, they are not stable under environmental conditions and are easily oxidized or dissolved in an acidic environment. In order to, overcome these problems, silica is commonly used as a protective shell for the coating of Fe3O4 MNPs and a magnetic core-shell nanostructure (Fe3O4@SiO2) is formed[16, 17]. Furthermore, silica prevents the agglomeration of Fe3O4 MNPs, and also the most surface of silyl groups, it is possible to modify their surface by different functional groups. It should be noted that the silica shell has a high porosity, is suitable for compatibility with the environment, and is an inexpensive material[18, 19].
α-Amino acids are natural compounds that make proteins in living systems. However, they can be considered as bifunctional organocatalysts from a catalytic point of view to activate both nucleophilic and electrophilic centers of the substrates through their carboxylic acid (-COOH) and amino (-NH2) functional groups with proper geometry, respectively[20]. On the other hand, the natural abundance of α-amino acids as well as their optic activity make them appropriate candidates for the preparation of nontoxic catalytic systems with proper biodegradability. Also, α-amino acids demonstrate low solubility in organic solvents and are pH-sensitive. Therefore, designing and preparation of catalytic systems using α-amino acid units would be very beneficial from a green chemistry perspective to be used in the chemical, pharmaceutical, food, biotechnology, medical industries. [21, 22]. The preparation of ionic liquids is another application of amino acids that can be mentioned[23, 24]. For example, a team of American researchers successfully synthesized three [EMIM][AA]-type of amino acid ionic liquids and immobilized them into nanoporous polymethylmethacrylate (PMMA) microspheres and used as robust sorbents for CO2[25]. Other researchers have used amino acids as a modulator in the preparation of zirconium and hafnium metal-organic frameworks (MOFs)[26]. Selenium nanoparticles (SeNPs) is an element used in the treatment of cancer and their major forms are organic and inorganic[27–29]. On the other hand, SeNPs are unstable and their use is limited by agglomerated, so biomolecules are used to stabilize these nanoparticles[30]. Researchers have shown that the interaction of NH3+ amino acid groups with negatively charged SeNPs can lead to the stability of these nanoparticles (SeNPs@AAs). Therefore, amino acids not only lead to stability and prevent the agglomeration of SeNPs, but also affect their anti-cancer function and increase their biological activity. These characteristics and wide applications of AAs encouraged our research team to use them as a catalyst and to advance the process in the preparation and identification of some of the six-membered heterocyclic rings.
Heterocyclic compounds are highly regarded and mainly synthesized due to their wide range of biological activities[31]. These compounds are used as key frameworks for the development of many therapeutic agents and play a prominent role in medicinal chemistry[32]. One of the best methods for preparing these bioactive compounds is the use of multicomponent reactions (MCRs).[33] In these reactions (domino processes), several starting materials (more than two reactants) react simultaneously and in one step at the presence of a catalyst and produce the desired product[34–37]. Multi-component reactions have unique advantages, such as the production of complex and diverse products through the formation of several bonds during an operation, without the need to isolate and purify the intermediates with high efficiency and high selectivity in the shortest time, together with the high atomic economy, therefore, they prevent the production of side and waste products during the reaction[38–41]. Polyhydroquinoline (PHQ) and 1,4-dihydropyridine (1,4-DHP) derivatives are some of the most important and oldest multi-component reactions that were first reported in 1882 by a German chemist named Arthur Hanztsch[42–44]. These compounds, due to pharmacological and biological activities, include the treatment of cardiovascular diseases such as high blood pressure (such as nicardipine, nifedipine, aponepidine, nimodipine, and depin, etc.) (Fig. 1)[45, 46], antiviral[47], antitumor[48], antimalarial[49], antibacterial[50], anti-cancer[51], blocked calcium channels[52] activities, as well as coenzyme NADH, have been widely considered for reducing carbonyl compounds and their derivatives[53] in recent decades. Therefore, according to the medical activities of the derivatives derived from the Hantzsch reaction to synthesize them, researchers to synthesize them used a variety of methods including the common heat[54], solar energy[55], and various catalytic systems such as molecular iodine[56], L- proline[57], magnetic nanoparticles Fe3O4[58], nanoparticles ZnO[59], polymers[60], Hy-zeolite[61]. Most of these processes suffer from disadvantages such as long reaction times, low yields, harsh conditions, high costs, feed high values, the use of hazardous catalysts, toxic and volatile solvents, and boring workup.
Over the past few decades, due to the energy crisis and environmental pollution, green chemistry has received a lot of attention[62]. The principles of green chemistry have led to the development of cleaner and milder processes, especially in chemical synthesis[63]. Sonochemistry and microwave-assisted chemistry are not only used to accelerate organic reactions but are also an environmentally friendly synthetic protocol, which we will discuss in the following[64, 65]:
Ultrasonic (US) radiation has recently emerged as a clean and green method to accelerate organic synthetic conversions[66, 67]. It generates high temperatures and pressures in a very short period of time. The main advantages of ultrasonic synthesis are high reaction rate, short reaction time, high efficiency, and mild reaction conditions[68, 69]. In fact, ultrasonic radiation initiates chemical reactions by creating sound cavities that are used to overcome molecular gravitational forces[70, 71]. The process of cavitation refers to the rapid growth and collapse of bubbles in a liquid in which a chemical reaction takes place inside and near the bubbles and has two main paths[72]. Energy consumption for partial heating is inseparable from any chemical process. Microwave (MW) radiation is one of the most desirable energy sources to overcome this problem. Compared to other conventional methods, synthesis by microwave radiation is a logical method in green chemistry that not only improves the reaction rate, efficiency, and reaction path but also reduces waste and conserves energy[73]. Microwave radiation often provides high selectivity, simplicity of operation, and optimal energy compared to traditional methods[64, 74]. The heat from microwave radiation is highly dependent on the dielectric properties of solutions compared to traditional heat, so compounds with a high dielectric constant tend to absorb microwave radiation compared to compounds with lower polarity[75]. According to the discussion and the mentality created in connection with green chemistry protocols, sonochemistry, and microwave-assisted chemistry techniques are known as promising tools and because of their quick and easy applications, high performance, and being environmentally friendly, they are able to expand the boundaries of green chemistry. Therefore, it has been considered by many chemists in recent years[76]. Therefore, due to the properties of heterogeneous catalysts, the properties and applications of AAs, MCRs, and Hanztsch derivatives, clean and new energy sources, and circumvention of environmental hazards, in order to achieve the goals of green chemistry, we were encouraged to prepare magnetic heterogeneous nanocatalyst for the synthesis of bio-active polyhydroquinoline (PHQ) and 1,4-dihydropyridine (1,4-DHP) derivatives. For this purpose, we successfully placed D-(−)-α-phenylglycine as a catalytic agent by 3-Chloropropyltrimethoxysilane (CPTES) on the surface of magnetic nanoparticles (MNPs) coated with silica (Fe3O4@SiO2@PTS-APG).
Then, by the aforementioned nanocatalyst, bioactive PHQ and 1,4-DHP derivatives were synthesized under ultrasonic wave irradiation in a short time with high efficiency in ethanol solvent through a one-pot four-component reaction (Fig. 2). In addition, the aforementioned catalyst can be recycled at least five times without significant loss of catalytic activity and used in the subsequent cycles of the reaction. In the end, a reaction mechanism has been proposed to prepare these biologically active derivatives.