A facile and efficient protocol for the synthesis of 2-amino-3-cyano-4 H-pyran derivatives at ambient temperature

Article history: Received June 28, 2013 Received in Revised form December 10, 2013 Accepted 30 January 2014 Available online 30 January 2014 An efficient and simple synthesis of some 2-amino-3-cyano-4H-pyran derivatives was developed by the one-pot and three-component reaction of aldehydes, ethyl acetoacetate, and malononitrile in the presence of ammonia as catalyst at room temperature. The reaction is rapid and clean, and gives the products in high yields. © 2014 Growing Science Ltd. All rights reserved.

Generally, 2-amino-4-aryl-3-cyano-4H-pyrans were synthesized by the cyclization of arylidenemalononitriles and active methylene compounds in the presence of organic bases such as piperidine, 14 pyridine, 15 triethylamine 16,17 .Most of these methods involve use of volatile solvents and require longer reaction time (~ 12 h) and difficult to recover catalyst.Recently, one-pot synthesis of these compounds has been reported using Mg/La mixed oxide 18 and MgO 19,20 as basic catalyst.More recently, we reported the multicomponent synthesis of 2-amino-4H-pyran derivatives in aqueous medium 21,22 .
Thus, in view of importance of this class of compounds, the development of a simple, efficient and versatile method for the preparation of 2-amino substituted 4H-pyrans is an active area of research and there is a scope for further improvement towards milder reaction conditions and higher product yields.Herein, we report a rapid and clean method for the synthesis of 2-amino-4H-pyran frame-works via a multi-component reaction of aromatic aldehydes, ethyl acetoacetate, and malononitrile in the presence of ammonia as catalyst at ambient temperature.

Results and discussion
In this procedure, a mixture of benzaldehyde derivatives 1 (0.5 mmol), ethyl acetoacetate (0.5 mmol), malononitrile (0.5 mmol) and 25% ammonia (0.2 mL) in ethanol (5 mL) is stirred at ambient temperature for 1-8 min until solid precipitates.The precipitated solid was filtered and purified by recrystallization from ethanol.The 2-amino substituted 4H-pyran derivatives 2a-i were obtained in good to excellent yields (Table 1).The synthesized compounds 2a-i are previously known and the structure of them were confirmed by comparison of physical characteristics and spectral data with those of known compounds 21 .Both electron-poor and electron-rich aldehydes were well tolerated.Despite using so much ammonia, no 1,4-dihydropyridine product was detected.a All reactions were conducted with aldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol), malononitrile (0.5 mmol), and ammonia 25% (0.2 mL) at room temperature in ethanol.b Isolated yields after recrystallization.

Conclusions
In summary, the one-pot three-component reaction protocol developed in the present study offers a fast and an efficient method for the synthesis of 2-amino substituted 4H-pyrans at room temperature.The experimental procedure is very simple and represents an attractive alternative to existing methods.This reaction protocol has the potential for developing combinatorial libraries.
The structures of compounds 2a-i were confirmed by the comparison of melting points and spectral data with those reported in the literature 21 .