Synthesis of ethyl-3-amino-1-aryl-1 H-benzo [ f ] chromeme-2-carboxylate derivatives promoted by DMAP

Article history: Received January 2, 2017 Received in revised form March 1, 2017 Accepted March 21, 2017 Available online March 21, 2017 An efficient route, convenient and environmentally friendly procedure for the synthesis chromenes derivatives have been developed via a three-component coupling and one-pot reactions of various aromatic aldehyde with malononitrile or ethyl cyanoacetate and phenols in the presence N,N-dimethylpyridin-4-amine (DMAP) in reflux conditions. In simple reaction conditions, the use of DMAP is explored as an easy workup and a green catalyst for the onepot three-component synthesis ethyl 3-amino-1-aryl-1H-benzo[f]chromene-2-carboxylate derivatives. © 2017 Growing Science Ltd. All rights reserved.


Results and Discussion
In continuation of our efforts toward the development of greener methodologies, [32][33][34][35][36][37][38] we report here in a simple, clean, and environmentally friendly process for the synthesis of ethyl-3-amino-1-aryl-1Hbenzo[f]chromene-2-carboxylate derivatives by reaction of various aromatic aldehydes with malononitrile or ethyl cyanoacetate and phenols (α-naphthol or β-naphthol ) in the presence DMAP, as catalyst and co-solvent (Scheme 1).In the beginning, we chose three-component reaction via ethyl cyanoacetate (1 mmol), pnitrobenzaldehyde (1 mmol), and 2-naphthol (1 mmol) (5a) as a model to determine the optimal reaction conditions.Reaction was performed in the presence of varying amounts of DMAP and at different temperatures.The best result is achieved in 0.5 mmol of DMAP at 120°C (Table 1, Entry 3).Also reaction was carried out in absence of the catalyst and was not observed product even after 5 h (Table 1, Entry 3).A summary of the optimization experiments is provided in Table 1.After optimization of the reaction conditions, we studied the generality of these conditions to other substrates.By using this method, different kinds of various aromatic aldehydes compounds were reacted with malononitrile or ethyl cyanoacetate and phenols to produce the corresponding chromenes derivatives under reflux conditions (Table 2).Finally, to show the merit of the present work, we summarized the results for the synthesis of chromenes derivatives obtained by other workers (Table 3).In contrast with other existing methods, the present methodology offers several advantages such as higher yields, a simple procedure, easy synthesis, simple work-up, does not require either hazardous acids or harsh reaction and greener conditions using DMAP as an efficient catalyst (Table 3).

Conclusions
In summary, we have developed an efficient and environmentally friendly method for the synthesis of 2-amino-2-chromenes in high yield, by use DMAP, as catalyst and co-solvent (additive).In contrast to the existing methods using potentially hazardous catalysts/additives, these procedures provide several advantages such as cleaner reactions, does not require either hazardous acids or harsh reaction, easier work-up, and an eco-friendly and promising strategy.

Generel
All the chemicals required for the synthesis of cheromene derivatives were purchased from Merck Company.A Bruker (DRX-400 AVANCE) NMR instrument was used to record the 1 H NMR and 13 C NMR spectra.All NMR spectra were determined in CDCl3 at ambient temperature; chemical shifts have been expressed in ppm.The IR spectra were recorded on a Shimadzu 8400 instrument (the samples as KBr disks for the range 400-4000 cm -1 ).Melting points were recorded with Electrothermal 9100 apparatus.Thin-layer chromatography was performed on Kieselgel 60 GF254 and visualization was accomplished by UV Lamp or iodine flask.Elemental analysis was carried out on a Thermo Finnigan Flash EA microanalyzer, and the results were found to match satisfactorily with the calculated and observed values.

General procedure for the synthesis of cheromene derivatives (4a-f and 5a-f).
To a mixture of various aldehydes, 1-naphthol or 2-naphlhol (5 mmol), ethyl 2-cyanoacetate or malononitril (5 mmol) and DMAP (0.5 mmol) in reflux conditions was stirred magnetically at 120 C for an appropriate time as mentioned in Table 2. Completion of the reaction was indicated by TLC (hexane:ethyl acetate, 8:2), after completion, appropriate amounts of hot EtOH (96%) was added and the mixture stirred for 10 min.Next, the resulting crude product was poured into crushed ice and the solid product, which separated was filtered, recrystallized from ethanol (96%, 3 ml) to get pure cheromene derivatives (4a-f and 5a-f).

Table . 1
. Screening of the Reaction Conditions for the Synthesis of (5a).

Table . 3
. Comparison of methods for the synthesis of chromenes derivatives.