A grinding-induced catalyst- and solvent-free synthesis of highly functionalized 1,4-dihydropyridines via a domino multicomponent reaction (original) (raw)

All the reactions were carried out at room temperature that is 28-32 0 C. Unless otherwise specified, all the reagents were purchased from Sigma-Aldrich Chemical Co, Lancaster and were used directly without further any purification. NMR spectra were obtained using the Brucker DRX 300MHz spectrometer. Chemical shifts (δ) are given in ppm relative to TMS, coupling constants (J) in Hz. IR spectra were taken on VARIAN FT-IR spectrometer as KBr pellets. Reactions were monitored by thin layer chromatography. Elemental analyses were performed on a Carlo Erba's 108 or an Elementar's Vario EL III microanalyzer. The reactions under microwave heating were carried out in a Biotage initiator 2.5 microwave system. Thin layer chromatography (TLC) carried out on 0.25 mm silica gel plates visualized with UV light. General procedure for synthesis of compounds 5(a-v), 6(a-e) A mixture of the appropriate aldehyde (1 mmol), aniline (1 mmol), DEAD (1 mmol), and malanonitrile(1mmol) was ground in a mortar and pestle at room temperature for the appropriate time. After two minute syrupy solution was observed, which was solidify on completion of reaction. After completion of the reaction give solid product 5a with high purity. General procedure for synthesis of compounds 7 (a-e) An oven dried microwave vial charged with Compound 5m(1 mmol) and cyclohexanone (3 mmol), SDS (30 mol%), in 3 ml of water take in vial tube of microwave and irradiated at 150 0 C with stirring under microwave for 15 min. After the completion of the reaction were monitored by thin layer chromatography. The reaction was diluted with a 5 mL of ethyl acetate and washed with saturated aqueous NH4Cl solution. The aqueous part was extracted with ether. The combined organic part was washed with brine and dried over Na2SO4. The solvent was evaporated to yield a crude residue, which upon purification via silica gel column chromatography using EtOAc/hexane gave pure product 7a.