One-pot Multi-component Synthesis of Amidoalkyl Naphthols with Potassium Hydrogen Sulfate as Catalyst under Solvent-free Condition

The multicomponent reactions are responsible for this higher efficiency (Bienaymè, H. C. et. al 2000), not only because of intrinsic aspects of the reaction such as superior atom economy (Trost, B. M., 1991, Trost, B. M. 1995, Trost, B. M. 2002), atom utilization and selectivity, as well as lower level of by-products, but also because of extrinsic aspects of the processing reaction, such as simpler procedures and equipment (Mitchell, M. C. et. al 2001, Jähnisch, K. et. al 2004), lower costs, time, and energy, as well as more environmentally friendly criteria. It is noteworthy that 1-carbamato-alkyl-2-naphthols can be converted to important biologically active 1-aminomethyl-2-naphthol derivatives by carbamate hydrolysis. The hypotensive and bradycardiac effects of these compounds have been evaluated (Szatmäri, I.; et. al 2004, Shen, A. Y. et. al 1999, Shaterian, H. R. et. al 2008).

Yb(OTf) 3 [17] , and Ce (SO 4 ) 2 [18] .However, some of the reported protocols suffer from certain drawbacks such as prolonged reaction time, use of carcinogenic solvent, unsatisfactory yield, high temperature (120~125 ) and use of toxic, highly acidic, expensive catalysts and additional microwave or ultrasonic irradiation.Therefore, the discovery of clean procedures and the use of green and eco-friendly catalysts with high catalytic activity and short reaction times for the production of amidoalkyl naphthols have gained considerable attention.
Potassium hydrogen sulfate is a cheap and efficient catalyst for the condensation reactions [19] .In the present study, a simple and green procedure for the synthesis of amidoalkyl naphthols by the condensation of aldehydes with β-naphthol, acetamide or urea in the presence of potassium hydrogen sulfate (KHSO 4 ) at 100 under solvent-free conditions is reported herein (Scheme 1).

OH Ar
ArCHO
After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water, and the resulting solid product was collected by filtration and was recrystallized from aqueous EtOH.

Result and Discussion
Benzaldehyde was selected as a representative aldehyde along with β-naphthol, acetamide and KHSO 4 which were reacted under solvent-free conditions at 100 in order to optimize the reaction conditions.The condensation of mixture of benzaldehyde 1a (1 mmol) with β-naphthol 2 (1 mmol) and acetamide 3 (1.1 mmol) in the presence of KHSO 4 (0.15 mmol) was carried out at 100 for 1.0 h under solvent free conditions.
The reaction proceeded smoothly and gave the corresponding amidoalkyl naphthol 4a as the sole product in 90% isolated yield (Table 1).Water was added to the reaction mixture and simply filtering the mixture to obtain the crude product, which was purified by crystallization from 30% aqueous ethanol as white solid.In order to demonstrate the generality of the process, some examples illustrating the present method for the synthesis of amidoalkyl naphthols 4 was studied (Table 1).
The reaction of β-naphthol 2 with various aromatic aldehydes bearing electron withdrawing groups (such as nitro, halo), electron releasing groups (such as, methyl or methoxy groups) and acetamide was carried out in the presence of KHSO 4 as a catalyst.
In all cases, clean and complete conversion leading to the corresponding amidoalkyl naphthols (4a~4k) as observed in shorter reaction times (0.5~1.5 h).Aromatic aldehydes with electron-withdrawing groups reacted faster than aromatic aldehydes with electron-donating groups, as would be expected.Similar results were obtained under the same conditions when urea was used in place of acetamide to give the respective compounds (4l~4q).

Conclusion
In conclusion, a novel and highly efficient methodology for the synthesis of amidoalkyl naphthols by condensation reaction of aldehydes, β-naphtol and acetamide or urea in the presence of catalytic amounts of KHSO 4 under solvent-free conditions is reported.This method offers significant advantages such as, high conversions, easy handling and shorter reaction times, which collectively makes it a useful and attractive process for the rapid synthesis of substituted amidoalkyl naphthols.

Table 1
Synthesis of Amidoalkyl Naphthols with Potassium Hydrogen Sulfate asCatalyst under solvent-free condition a All known compounds were characterized by comparing their spectral data with those reported b Isolated yields.