A Facile Synthesis of New 2-Amino-4H-pyran-3-carbonitriles by a One-Pot Reaction of α, α′-Bis(arylidene) Cycloalkanones and Malononitrile in the Presence of K2CO3

A rapid and environmentally friendly method is developed for the synthesis of a series of new substituted 2-amino-4H-pyran-3-carbonitriles through a one-pot condensation of malononitrile and α, α′-bis(arylidene) cycloalkanones in ethanol by using K2CO3 as a catalyst. Short experimental reaction times, excellent yields, no need to use cumbersome apparatus for purification of the products, and inexpensiveness and commercially availability of the catalyst are the advantages of this method.


Introduction
In the past few decades, the synthesis of new heterocyclic compounds has been a subject of great interest due to the wide applicability of them. Heterocyclic compounds occur very widely in nature and are essential to life. The importance of multicomponent reactions in organic synthesis has been recognized, and considerable efforts have been focused on the design and development of one-pot procedures for the generation of libraries of heterocyclic compounds [1,2]. 4H-Pyrans and their derivatives are of considerable interest due to their pharmacological activities [3], such as spasmolytic, diuretic, anticoagulant, anticancer, and antianaphylactic activity [4][5][6]. Moreover, 4H-pyrans are useful intermediates for synthesis of various compounds, such as pyranopyridine derivatives [7], polyazanaphthalenes [8], pyranopyrimidines [9], and pyridin-2-ones [10].
Furthermore, 4H-pyrans represent building blocks of a series of natural products [11,12]. A number of 2amino-4H-pyrans are used as photoactive materials [13], pigments [14], and potential biodegradable agrochemicals [15], and consequently, numerous methods have been reported for the synthesis of these compounds. Thus, the synthesis of 4H-pyran is of much importance to organic chemists. Several methods have been reported for the synthesis of pyran derivatives via a three-component condensation of β-dicarbonyl compounds with aldehydes and malononitrile [16]. From the literature, we observed that very few catalysts have been used for the synthesis of 2-amino-4H-pyran-3-carbonitriles base on the reactions of α, α -bis(arylidene) cycloalkanones with malononitrile, for example, NaOH/piperidine [17], KF-Al 2 O 3 [18], and hexadecyltrimethyl ammonium bromide (HTMAB) [19]. However, these methods show varying degrees of success as well as limitations such as prolonged reaction times, low yields, and use of toxic solvents. Thus, the development of an alternate milder and clean procedure is highly demanding for the synthesis of 2-amino-4H-pyran-3-carbonitriles, which surpasses those limitations. Herein, we planned to synthesis of these compounds using sequential reactions of α, α -bis(arylidene) cycloalkanones and malononitrile in the presence of K 2 CO 3 as a catalyst in ethanol under reflux conditions (Scheme 1).
Nowadays, organic reactions in ethanol without the use of harmful organic solvents have attracted much attention, because ethanol is a cheap, safe, and environmentally benign solvent [7]. In recent years, K 2 CO 3 has been considered as an efficient, inexpensive, and readily available catalyst for several organic transformations [20,21].

Results and Discussion
In continuation of our studies on the development of inexpensive and environmentally benign methodologies for organic reactions [22][23][24], herein we report a highly versatile and efficient synthesis of 2-amino-4H-pyran-3-carbonitriles 3a-q (Scheme 1) from α, α -bis(Arylidene) cycloalkanone 1, malononitrile 2 and catalytic amounts of K 2 CO 3 . In a typical reaction, a mixture of 1 and 2 (1 : 1) equivalents, respectively, and K 2 CO 3 (cat.) was refluxed in ethanol for 5-60 min. The results are summarized in (Table 1). The formation of the compounds 3 was assumed to proceed via formation of a Michael adduct intermediate followed by cyclization according to Scheme 2. A α, αbis(arylidene) cycloalkanones 1 was firstly condensed with malononitrile 2 to afford the intermediate 4, this step can be regarded as a Michael addition. Then, the intermediate 5 cyclized by nucleophilic attack of the OH group on the cyano (CN) moiety and gave the intermediate 6. Finally, the expected products 3 were afforded (Scheme 2) [17][18][19].
To test the catalysts, the reaction of α, α -bis(arylidene) cyclohexanone and malononitrile in ethanol was selected as a model reaction. The scope and the generality of the present method were then further demonstrated by the reaction of various α, α -bis(arylidene) cycloalkanones with malononitrile and K 2 CO 3 . In all cases, good yields with good selectivity were obtained. The catalyst plays a crucial role in the success of the reaction in terms of the rate and the yields. The present methodology afforded high yields of the products within short times (5-60 min). The results ( Table 1, entries 1-17) indicated that substrates 1 bearing both electron-donating groups (such as alkoxy and methyl) and electron-withdrawing groups (such as halide) can be involved in this one-pot synthesis to afford desired products 3 with high yields. Thus, it should be concluded that the electronic nature of the substituents has no significant effect on this reaction.
In order to show the merits of K 2 CO 3 over other catalysts reported in the literature, results for the synthesis of 2-amino-4H-pyran-3-carbonitriles obtained using K 2 CO 3 as the catalyst were compared with those obtained using other catalysts. Table 2 clearly shows that K 2 CO 3 appears to promote the reaction more effectively than a number of other catalysts, particularly in terms of the time and yield required to complete the reaction.

Conclusion
In conclusion, the present method is a simple and environmentally friendly procedure for the synthesis of a series of new 2-amino-4H-pyran-3-carbonitriles using catalytic amount of K 2 CO 3 . The simple experimental procedure, short reaction times, excellent yields of products, mild reaction condition, easy purification, economic availability of the catalyst, and green standard are the advantages of this method.
The structure of the products was deduced from their IR, 1 H NMR, 13 C NMR, and elemental analysis. The spectral (IR, 1 H NMR, 13 C NMR) and analytical data of unknown compounds are given below. 7, 3 g). Cream 8, 3 h). Cream try 10, 3 j). Cream