The reaction of N, N’-(1, 4-phenylene) bis (2-cyano-3-(dimethylamino) acrylamide) (2) with resorcinol, a-naphthol, b-naphthol, dimedone and indandione in acetic acid afforded bisCHROMENE derivatives 4, 6, 8, 12 and 14, respectively. Similarly, treatment of 2 with barbituric acid, thiobarbituric acid and 3-methyl-1-phenyl-1H-pyrazol-5 (4H)-one to give pyrano [2, 3-b] pyrimidine 16, 18, and pyrano [2, 3-c] pyrazole 20 derivatives. Moreover, 2 react with thiocyanoacetamide to afford 2-pyridone derivative24. The newly synthesized compounds were evaluated as antitumor activities. The results showed that four compounds, namely 4, 10, 18 and 24, displayed promising in vitro antitumor activity in the four cell lines assay.

Synthesis of 4H-CHROMENE and its derivatives has attracted great interest due to their biological and pharmacological activities. Here, a simple and practical method was employed for synthesizing 3,4-Dihydropyrano[c]CHROMENE derivatives, which have found medicinal applications. This method involves reacting 4-hydroxycoumarin and malonitrile with an aromatic aldehyde in the presence of Fe3O4@SiO2-SO3H nanocatalyst and methanol as a green solvent. The prepared catalyst was characterized by FT-IR, XRD, BET, VSM, and SEM. The reaction was optimized for four variables of benzaldehyde derivatives, solvent type, temperature, and catalyst loading. The highest 3,4-Dihydropyrano [c]CHROMENE yield of 98% was obtained with 1 mmol of 3-nitrobenzaldehyde and 0.05 g of Fe3O4@SiO2-SO3H at 80 °C in methanol solvent after 2h. Notably, the saturation magnetization of Fe3O4@SiO2-SO3H nanocomposites is sufficient for magnetic separation using an external magnet. This method yields excellent results with easy separation of catalyst. The recyclability test for five consecutive runs showed negligible loss in catalytic activity.

Sucrose is applied as an efficient catalyst for the three-component reaction consisting of aromatic aldehydes, malononitrile and resorcinol in a mixture of water and ethanol media as green solvents. The advantages of this method are excellent yeild, inexpensive catalyst and more environmentally friendly. Mechanistic insight into the synthesis of 2-amino-4H-CHROMENE included spectral kinetics approaches is revealed. From the temperature, concentration and solvent studies, the activation energy (Ea= 102 kJmol-1) and the related kinetic parameters (DG¹= 41 kJmol-1, DS¹= 195 Jmol-1 and DH¹= 99 kJ mol-1) are calculated. The first step of proposed mechanism is recognized as a rate-determining step (k1) and this is confirmed based upon the steady-state approximation.

A series of 2-amino-4- (nitroalkyl) -4H-CHROMENE-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC50 values less than 30 mg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC50 values in the range of 3.46-18.76 mg/mL, being more potent than etoposide against all tested cell lines.