## 4 Synthesis of Amidoalkyl Naphthols via Multicomponent Mannich Condensation
### Heterogeneous Catalysis
#### 4.2.1 Nanomaterials as Catalysts
Yields of up to 97% have been achieved under solvent-free conditions in 0.1 g/1 mmol catalyst/substrate ratio [74]. A series of amidoalkyl naphthols was prepared by [PERSON] et al., via a reaction of 2-naphthol, various aldehydes, and amides in the presence of nickel nanoparticles as a catalyst under solvent-free conditions at 100 \({}^{\circ}\)C. The reported yields ranged from 35 to 95% and the reaction times were between 12 and 40 min [75]. Phosphotungstic acid supported on functionalized graphene oxide nanosheets (GO-SiC\({}_{3}\)-NH\({}_{3}\)-H\({}_{2}\)PW) exhibited good catalytic activity and recyclability in a catalyst/substrate ratio of only 0.03 g/1 mmol. The reactions were carried out in refluxing ethanol and rendered 80 to 94% yields in 10-20 min [76]. [PERSON] and colleagues also prepared functionalized graphene oxide nanosheets containing a phosphomolybotic counterion. In contrast with the previous work, this catalyst operated under solvent-free conditions and shorter reaction times (2-10 min), while maintaining a similar level of recyclability [77]. Another example of a recyclable graphene oxide catalyst for the preparation of amidoalkyl naphthols was that reported by [PERSON] et al., [78], in which graphene oxide was simultaneously functionalized with 2-aminobenzzothiazole and phosphoric acid. This method provided several advantages such as short reaction times (15-35 min), solvent-free conditions, simple work-up, and high yields (86-97%). The stability and recoverability of the catalyst were also examined in five cycles which showed no considerable loss of activity. Several Fe\({}_{3}\)O\({}_{4}\)-based nanocatalysts have been shown to exhibit good catalytic activity towards the synthesis of amidoalkyl naphthols under solvent-free conditions. In all instances the amidoklyl naphthols were isolated in good to excellent yields in short reaction times. Notably, this class of catalysts exhibited a very good level of recyclability [21; 79; 80; 81; 82; 83; 84]. Furthermore, the biological activity of some of the obtained products was examined against _Staphylococcus aureus_ and _Escherichia coli_. Seven of the synthesized compounds showed better activity against _S. aureus_ than the standard (gentamicin) [21]. [PERSON] and [PERSON] used tin(IV) oxide nanoparticles (nano-SnO\({}_{2}\)) as a reusable catalyst for the preparation of several derivatives in refluxing aqueous medium. The targeted amidoalkyl naphthols were isolated in high yields (90-96%) within minutes using only 0.02 g/1 mmol catalysts/substrate ratio [85]. Sulfonic acid implemented on a silica-coated cobalt ferrite core was applied as a recyclable catalyst for the preparation of amidoalkyl naphthols under solvent-free conditions at 80 \({}^{\circ}\)C. The use of 0.05 g/1 mmol catalyst/substrate ratio rendered good to excellent yields in 10-20 min [86]. [PERSON] et al., explored bis(benzoyl acetone ethylene diimine) complex of nickel(II) supported on magnetite silica nanoparticles as a catalyst under solvent-free conditions. Although relatively long reaction times (3.5-4 h) were required compared with other classes of nanocatalysts, the authors achieved the synthesis of 11 amidoalkyl naphthols in very good yields using only 1.5 mol% of catalyst [87]. A reusable bifunctional SBA-amino-amido-carboxylic acid rendered 12 amidoalkyl naphthols in high yields (85-91%) in a very short reaction time (10 min). However, this catalyst required the use of refluxing ethanol as a reaction medium [88]. CdCl\({}_{2}\)-containing filamentous silica nanoparticles [89] and CuFe\({}_{2}\)O\({}_{4}\)/KCC-1/PMA [90] also provided access to very high yields of a similar scope to amidoalkyl naphthols. In comparison with the bifunctional SBA-amino-amido-carboxylic acid, these catalysts operated under solvent-free conditions and lower catalyst loadings. [PERSON] and co-workers made use of phenyltetrazolethiol-based Ni complex as a recyclable heterogeneous nanocatalyst.