1 Introduction

Water is a versatile solvent in many ways, and performing organic reactions in this medium is now of great interest [1]. It is undoubtedly the most inexpensive among various solvents used in organic synthesis. The lack of inflammable, explosive, mutagenic, and carcinogenic properties is a favorable aspect of water in academic laboratories as well as in industry. Furthermore, water is now regarded as one of the most suitable solvents from an environmental point of view [2]. 2-Amino-4H-chromenes and their derivatives are of significant importance as they possess a wide range of biological activities, such as antimicrobial [3], antiproliferative [4], sex pheromone [5], antitumor [6] ones; they can be used in cancer therapy, and are beneficial to the central nervous system [7]. Several methods have been reported for the synthesis of 2-amino-4H-chromene derivatives using malononitrile, resorcinol and aldehydes. Various catalysts, such as piperidine [8], cetyltrimethylammonium bromide (CTABr) [9], TFE [10], Ca(OH)₂ [11], MgAl/HT [12] and tungstic acid functionalized mesoporous SBA-15 [13] have been used for these reactions. Also, the Yb(OTf)₃-catalyzed reactions of 5-alkylidene Meldrum's acids with phenols for the one-pot synthesis of 2-substituted chromones was reported [14]. Most of these methods require a long reaction time, high temperatures, and afford unsatisfactory yields. In order to make the reaction simple and green, herein, K₂CO₃ has been successfully applied to perform the three-component reaction of resorcinol, 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone with benzaldehydes and malononitrile in water at 70 °C to provide a series of novel 2-amino-3-cyano-4H-chromene derivatives in excellent yields.

2 Results and discussion

A variety of 2-amino-3-cyano-4H-chromenes was prepared from resorcinol 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone with benzaldehydes and malononitrile in the presence of K₂CO₃ (25 mol%) in water as a green solvent at 70 °C in excellent yields (Table 1, entries 1–11). It is worth mentioning that the corresponding 2-amino-3-cyano-4H-chromenes were isolated by crystallization from the crude filtrate. The reactions worked well with almost all benzaldehydes with electron-donating or electron-withdrawing substituents. During the synthesis of the 2-amino-4H-chromene derivatives from resorcinol, the product 2-amino-5-hydroxy-4H-chromene was not observed; this may be due to steric hindrance by the two adjacent ortho-hydroxyls and the enol to keto tatumeric forms between hydroxyl groups in resorcinol (Table 1, 4a–e) [15]. In the reaction of 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone with benzaldehydes and malononitrile, the substituted group enters the 2-position between the hydroxyl groups in the 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone molecule and the product 6-acetyl-2-amino-5-hydroxy-4H-chromene or 2-amino-6-benzoyl-5-hydroxy-4H-chromene was observed, whereas the expected 6-acetyl-2-amino-7-hydroxy-4H-chromene or 2-amino-6-benzoyl-7-hydroxy-4H-chromene as a regioisomer was not produced (Scheme 1). The regioselectivity of 5a–g may be defined by the chelation of the o-hydroxy group in the 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone molecule via intramolecular hydrogen bond formation between the acetyl or the benzoyl carbonyl group with the adjacent hydroxyl group and this chelation makes more reactive the 2-position of the 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone molecule that reacted with substituted 2-benzylidenemalononitrile intermediates to give 2-amino-5-hydroxy-4H-chromene derivatives (Table 1, 5a–g) [11].

In a plausible mechanism, it is assumed that the reaction may proceed initially through a Knoevenagel condensation between arylaldehyde and malononitrile to form intermediate I. Next, a Michael addition of activated resorcinol derivative II (K₂CO₃ abstracts an acidic proton from the resorcinol derivative) to intermediate I affords III. Intermediate III converts to IV after tautomerisation. Then, intermediate IV converts into V via deprotonation of an acidic proton of the resorcinol derivative by K₂CO₃. Finally, the desired product VII is obtained after intramolecular cyclization and rearomatization from VI (Scheme 2).

3 Conclusion

We have developed an efficient and one-pot procedure for the synthesis of some novel 2-amino-3-cyano-4H-chromene derivatives by three-component condensation of resorcinol, 1-(2,4-dihydroxyphenyl)ethanone or 2,4-dihydroxybenzophenone, benzaldehydes and malononitrile using K₂CO₃ as a cheap and efficient catalyst in water as a green solvent.

4 Experimental

All chemicals were purchased from Merck chemical company. The melting points were recorded on an electrothermal melting point apparatus. The NMR spectra were recorded in CDCl₃ with TMS as an internal standard on a Bruker Avance DRX 400 MHz spectrometer. FT–IR spectra were determined on an SP-1100, P-UV-Com instrument. The products were separated by simple filtration and identified by FT–IR, ¹H NMR and ¹³C NMR spectra.

Acknowledgments

We are grateful to Islamic Azad University, Rasht Branch, for financial assistance of this work.