Pyrano derivatives are heterocycles found in many natural products ^[1]. Biologically these heterocyclic compounds possess antioxidant,spamolytic,anticancer,antibacterial,antianaphylactic, and anti-HIV activity ^[2]. Furthermore,these compounds exhibit unique pharmacological activities including treatment of TNFa-mediated human inflammatory diseases,Alzheimer’s disease, amyotrophic lateral sclerosis,Huntington’s disease,and Parkinson’s disease ^[3]. However,the reported methods still have drawbacks; specifically,toxic organic solvents are often used. The use of a large volume of such solvents causes environmental damages,since they are utilized in larger quantities than the solutes they carry,and are released into the environment through evaporation and leakage. Compared with the harmful effects of organic solvents,water has the advantages of low cost,safety,and environmental friendliness ^[4].

Diammonium hydrogen phosphate (DAHP) is an inexpensive, water-soluble,non-toxic,and commercially available compound that can be used in the laboratory without special precautions ^[5]. This reagent has been used in important manufacturing processes, such as fire-proofing textiles,paper,wood,and vegetable fibers ^[6]. There are a few reports regarding the application of DAHP in the preparation of organic compounds ^{[7, 8]}. Thus,continuing our research on new one-pot reactions ^[9],we considered DAHP to be ideal for effecting the synthesis of 1,4-phenylene-bis(4H-pyran) derivatives and (naphthalen-2-yl)-4H-pyran derivatives in aqueous media via a three-component reaction of different nucleophiles,aromatic aldehydes,and malononitrile. Some of these compounds have already been prepared in this way but required heating in a large volume of absolute ethanol in the presence of piperidine ^[10]. Herein,we describe our very simple, green,and efficient route using a catalytic amount of DAHP in aqueous media at room temperature. 2. Experimental

Mps were determined using open glass capillaries on a Gallenkamp melting point apparatus and were uncorrected. The IR spectra were recorded with a Shimaduz 408 instrument using potassium bromide pellets. The 1H NMR (400 MHz) and ¹³C NMR (100 MHz) spectra were measured in DMSO-d6 using a Burker AM 400 with TMS as an internal standard. 2.1. Synthesis of 4a–l

A solution of terphthalaldehyde 1 (1 mmol),malononitrile 2 (2 mmol),nucleophile (2 mmol),and DAHP (20 mg,15 mol%) in H₂O (10 mL) and EtOH (5 mL) was stirred at room temperature for an appropriate period of time. After the completion of the reaction, the solid product was collected by filtration and purified by washing with aqueous ethanol. 2.2. Synthesis of 6a–f

An equimolar mixture (1 mmol) of naphthalaldehyde (5), malononitrile (2),and nucleophile 6 in 5 mL of saturated K₂CO₃ solution was taken in a beaker and subjected to MW at 600 W. On the completion of the reaction as monitored by TLC examination at an interval of 1 min,the reaction mixture was cooled and triturated with water. The product was collected by filtration and recrystallized from EtOH/H₂O.

The compounds 4k ^[11] and 4b–f ^[12] are known while characterization of the new products is listed in Supporting Information. 3. Results and discussion

Synthesis of 2-amino-4H pyran-3-carbonitrile was achieved by the three-component one-pot reaction of terephthaldehyde 1, malononitrile 2,and nucleophiles 3 (i.e.,3-aminophenol,acetylacetone, cyanoacetamide,3-acetylpyridine,barbaturic,dimidone, cyanothioacetamide,resorcinol,pyrazoline-5-one(H,ph),or thiobarbaturic) in the presence of 15 mol% catalyst. The reaction was carried out in aqueous ethanol (H₂O/EtOH) at room temperature using DAHP as a catalyst to give products in good to high yields (Scheme 1).

Scheme 1

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Scheme 1.The synthesis of compounds 4a–l.

To take advantage of the elaborated green protocol a small amount of ethanol was added to the reaction mixture to produce sufficiently pure product. This procedure avoided the use of expensive silica gel chromatography,and a small amount of ethanol instead of chromatographic eluent seemed to be a good trade-off from the green chemistry perspective. In order to optimize the conditions,we used terphthalaldehyde,resorcinol, and tested various amounts of DAHP as a catalyst. After 2 h with 5, 10,and 15 mol% of DAHP,yields of 34 and 93% respectively,were obtained. In the absence of DAHP the reaction did not occur. To show that DAHP is an efficient catalyst rather than just a mild base, we tried the reaction in solution at pH 7,8 but no reaction progression was observed. Substituents on the aromatic ring of nucleophiles did not show any electronic effects in terms of yields under these reaction conditions. The structures of compounds 4a–l were deduced from their high-field 1H NMR,¹³C NMR,and IR spectral data,and also by mass spectrometry. All of the products exhibited a singlet in ¹H NMR spectra at about δ 4.34–5.56 for H-4 and also a distinguishing peak at δ 55.90–58.86 for C-4 in the 13CNMR spectra. The mass spectra displayed molecular ion peaks with appropriate values.

Encouraged by this successful condensation,we next attempted to use the new protocol in the condensation of naphthalaldehyde (1 equiv.),malononitrile (1 equiv.),and resorcinol (1 equiv.) as a model reaction in the presence of K₂CO₃ under MW irradiation. In our exploratory experiments,we observed that the reaction occurred and the aldehyde underwent the three-component condensation smoothly to afford 2-amino-4-(naphthalen-2-yl)-4H-pyran-3-carbonitrile derivatives in high yields (Scheme 2).Thereafter,a series of differently substituted pyrano derivatives 6a–f were prepared from different nucleophiles bearing electronwithdrawing and electron-donating groups. All the utilized functionalities were found to be compatible under the reaction conditions.

Scheme 2

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Scheme 2.The synthesis of compounds 6a–f.

In summary,we have demonstrated that diammonium hydrogen phosphate (DAHP) is an efficient catalyst for the one-pot threecomponent synthesis of 1,4-phenylene-bis(2-amino-4H-pyran-3- carbonitrile) derivatives. Also we have developed a novel protocol that provides an efficient and environmental friendly synthetic route for the synthesis of 2-amino-4-(naphthalen-2-yl)-4H-pyran- 3-carbonitrile derivatives using MW irradiation. Appendix A. Supplementary data

Supplementary data associated with this article can be found,in the online version,at http://dx.doi.org/10.1016/j.cclet.2013.11.041.