Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al2O3/MeSO3H

A highly efficient, simple and environmentally friendly synthesis of 3-arylquinolines has been developed in the presence of Al2O3/MeSO3H via one-pot reaction of anilines and styrene oxide. This methodology provides very rapid access to 3-arylquinolines in good to excellent yields under solvent-free conditions at room temperature in air.


Introduction
Quinoline derivatives have received considerable interest because they are found in numerous natural products with many biological activities. They have also played an important role in medicinal chemistry due to their pharmacological properties [1][2][3][4]. Transition metal-catalyzed processes [5][6][7][8] and metal-free paths [9][10][11] are two general approaches for the synthesis of this type of compounds. However, the existing methods suffer from complicated multistep processes, limited availability of substrates, toxic organic solvents, long reaction times, expensive catalyst and low regioselectivity in some cases.
One current area of modern synthetic organic chemistry is the development of powerful and effective practical procedures that minimize the requisite time, temperature, labour, and cost for the desired transformations [12,13]. The tandem reaction of anilines with styrene oxide via C-C cleavage is the efficient synthetic route to quinolones [1]. The reaction was performed using FeCl 3 as catalyst in 1,4-dioxane as solvent at 110 °C for 12 h. According to the significance of this progress, we have decided to re-optimize it. The mixture of Al 2 O 3 and MeSO 3 H has been previously used as an effective and mild reagent for organic transformations [14].
In continuation of our studies to develop new synthetic methods for heterocycles [15][16][17][18][19], herein, we disclose a novel route to the synthesis of 3-arylquinolines from aniline derivatives and styrene oxide at room temperature under solvent-free conditions (Scheme 1).  Scheme 1 briefly compares the procedure reported by Wang and co-workers and our method. As it can be seen, the reaction can be performed under very short reaction time and low temperature.

Results and Discussion
To exploit optimized conditions for the synthesis of quinolines, the reaction of 3,4-dimethylaniline (1, 1.0 mmol) and styrene oxide (2, 2.0 mmol) in an open atmosphere was chosen as a model reaction (Table 1).
Control experiments showed that in the absence of Al 2 O 3 and MeSO 3 H, no quinoline 3a was observed (  (Table 2). In continuation of our study, aliphatic epoxides were also checked; unfortunately, they were not applicable for the preparation of quinolines. All novel and known compounds were characterized by their melting points, IR, 1 H NMR, 13 C NMR and mass spectra.
In order to recover Al 2 O 3 , the mixture was diluted with ethyl acetate and filtered. The solid on the filter paper was washed by ethyl acetate and evaporated. It should be noted that only Al 2 O 3 was reused and it is necessary to add MeSO 3 H again for each cycle with recovered Al 2 O 3 . The recycled catalyst could be reused five times without any significant loss in activity ( Figure 1).

Conclusion
In conclusion, Al 2 O 3 and MeSO 3 H exhibited an excellent reactivity in the one-pot synthesis of 3-arylquinolines using anilines and styrene oxide. The methodology has the advantages of good to excellent yields, readily available starting materials, short reaction time, mild and solvent-free conditions. The method utilizes nonexpensive reagents and starting materials, as well. Further work is in progress to extend the scope and to investigate mechanism aspects of this reaction.

Experimental
Instrumentation, analysis and starting material  Table 2. After completion of the reaction, the mixture was diluted with ethyl acetate, and filtered. The filtrate was washed with a solution of NaHCO 3 (5%; 3 × 30 mL) and then 30 mL deionized water. The solution was dried over magnesium sulfate; the solvent was evaporated to give the crude product, which was purified by silica gel column chromatography employing n-hexane/ethyl acetate (10:1) as eluent.

Supporting Information
Supporting Information File 1 Additional experimental and analytical data and NMR spectra.