An Efficient Solvent-Free Protocol for the Synthesis of 1-Amidoalkyl-2-naphthols using Silica-Supported Molybdatophosphoric Acid

A highly efficient, green and simple solvent-free method for the synthesis of 1-amidoalkyl-2-naphthols via one-pot multi-components condensation of 2-naphthol, aromatic aldehydes and amides in the presence of catalytic amount of silica-supported molybdatophosphoric acid (H3PMo12O40.xH2O/SiO2, 3.17 mol%) is described. The reactions proceed rapidly and the title compounds are produced in high to excellent yields.

Recently, the use of catalysts and reagents supported on solid supports under solventfree conditions has been developed because such reagents not only cause to simplify the purification processes but also help to prevent the releasing of toxic reaction residues into the environment [32][33][34][35][36][37][38][39][40][41][42] .Moreover, due to moisture sensitivity of some reagents; application of them in organic reactions is difficult.This problem can be solved by supporting of them on solid supports [32][33][34][35][36][37][38][39][40][41][42] .Handling of solid-supported reagents is also easy.Silica gel is one of the most interesting solid supports and is inexpensive, reusable, commercially available and environmentally benign which has been used in various organic transformations [36][37][38][39][40][41][42] .Consequently, it is noteworthy that the combination of safe supported-catalysis with the use of solvent-free technique represents a suitable way toward the so-called "ideal synthesis" 32-42.In this paper, we report a new, efficient and simple method for the synthesis of 1-aminoalkyl-2-naphthols from 2-naphthol, aromatic aldehydes and amides in the presence of H 3 PMo 12 O 40 .xH 2 O/SiO 2 as a green catalytic system under solvent-free conditions (Scheme 1).It is worth noting that this method has none of the above-mentioned disadvantages at all.

Experimental
All chemicals were purchased from Merck or Fluka Chemical Companies.Silica gel 60, 0.063-0.200mm (7-230 mesh ASTM) was applied as support.The structures of known compounds were identified by comparison of their melting points and spectral data with those in the authentic samples.The 1 H NMR (250 or 300 MHz) and 13

General procedure for the synthesis of 1-amidoalkyl-2-naphthol derivatives
To a well-ground mixture of 2-naphthol (2 mmol, 0.288 g), amide (2.4 mmol) and H 3 PMo 12 O 40 .xH 2 O/SiO 2 (0.350 g, 3.17 mol%) in a 10 mL round-bottomed flask connected to a reflux condenser, was added aldehyde (2 mmol) and the resulting mixture was stirred in an oil-bath (120 °C) for the appropriate time.After completion of the reaction, as monitored by TLC, the reaction mixture was cooled to room temperature, and was added to a column chromatography on silica gel and eluted with EtOAc/n-hexane (1/2) to give pure product.

Scheme 1
However, in these conditions, a highly sticky reaction mixture was obtained and the product was obtained in 79% yield after 15 min.Increasing the reaction time or the temperature didn't improve the yield.The synthesis of 1-amidoalkyl-2-naphthol 1 was also examined in different solvents including DMF, DMSO, NMP, HMPTA, THF, EtOH and EtOH/H 2 O (1/1, v/v); but, low yields (34-65%) of the product were obtained in long reaction times (2-4 h) in the solution conditions.The yield increased to 91% when the reaction was carried out in the presence of silica-supported H 3 PMo 12 O 40 .xH 2 O (33% w/w) as catalyst under solvent-free conditions (Table 1, entry 3).To choose suitable amount of H 3 PMo 12 O 40 .xH 2 O/SiO 2 as well as reaction temperature, the multi-components condensation of 2-naphthol (2 mmol), benzaldehyde (2 mmol) and acetamide (2.4 mmol) was tested using different amount of the catalytic system at range of 100-130 °C in the absence of solvent.The results are summarized in Table 1.As it can be seen in Table 1, the reasonable results were obtained in the presence of 0. To assess generality and scope of the method, 2-naphthol was reacted with various aromatic aldehydes and amides.The results are displayed in Table 2.As it is shown in Table 2, using this method, all aldehydes including benzaldehyde as well as aromatic aldehydes possessing electron-withdrawing substituents, electron-releasing substituents or halogens on their aromatic rings afforded the desired 1-amidoalkyl-2-naphthols in high to excellent yields and in short reaction times (Table 2, compounds 1-13).The method was also successfully worked when benzamide or nicotinamide was used instead of acetamide in the reaction (Table 2, compounds 14-16).

Conclusion
In summary, we have developed a new protocol for the synthesis of 1-aminoalkyl-2naphthols as biologically interesting compounds via the one-pot multi-components condensation of 2-naphthol, aromatic aldehydes and amides using silica-supported H 3 PMo 12 O 40 .xH 2 O under solvent-free conditions.The advantages of this method are efficiency, generality, high yield, relatively short reaction time, cleaner reaction profile, simplicity, ease of preparation of the catalytic system, ease of product isolation, and compliance with the green chemistry protocols.
a Isolated yield.

Table 3 .
Comparison of the results of the condensation of 2-naphthol with benzaldehyde and acetamide catalyzed by H 3 PMo 12 O 40 .xH 2 O/SiO 2 with those obtained by the recently reported catalysts.
a Turn-over frequency .bOur catalyst.