Exploring catalyst and solvent effects in the multicomponent synthesis of pyridine-3,5-dicarbonitriles.
The effects of an ionic base, tetrabutylammonium hydroxide (TBAH), and an amine base, piperidine, on the direct synthesis of pyridine-3,5-dicarbonitriles using a multicomponent reaction (MCR) from aldehydes, malononitrile, and thiols were systematically investigated. The amine base showed better results when the MCR was performed in ethanol, whereas employing the ionic base in acetonitrile resulted in similar yields but in a much shorter reaction time. A modified protocol to overcome the difficulty in the direct synthesis of pyridine-3,5-dicarbonitriles via the MCR from sterically hindered aldehydes using either base was realized by changing the reaction solvent from ethanol to acetonitrile. Mechanistically, the two catalysts were found to each promote different pathways in the final oxidation step of the penultimate product, 1,4-dihydropyridine 6. A reaction intermediate, Knoevenagel adduct 7, plays the major role in the amine base-catalyzed system, while in the presence of an ionic base, aerobic oxygen acts as the primary oxidant.
Guo
Kai
K
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, UK.
Thompson
Mark J
MJ
Chen
Beining
B
D000097:Acetonitriles / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D004095:Dihydropyridines / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000097:Acetonitriles; D000447:Aldehydes; D000588:Amines; D004095:Dihydropyridines; D007477:Ions; D009570:Nitriles; D016877:Oxidants; D011725:Pyridines; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D012997:Solvents; D013438:Sulfhydryl Compounds; D000431:Ethanol; C038806:1,4-dihydropyridine; C009405:tetrabutylammonium; C000945:dicyanmethane; D010100:Oxygen; C032159:acetonitrile