Efficient sonochemical synthesis of alkyl 4-aryl-6-chloro-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylate derivatives

Abstract

A facile, efficient and environment-friendly protocol for the synthesis of 6-chloro-5-formyl-1,4-dihydropyridine derivatives has been developed by the convenient ultrasound-mediated reaction of 2(1H)pyridone derivatives with the Vilsmeier-Haack reagent. This method provides several advantages over current reaction methodologies including a simpler work-up procedure, shorter reaction times and higher yields.

Eco-Friendly Methodology to Prepare N-Heterocycles Related to Dihydropyridines: Microwave-Assisted Synthesis of Alkyl 4-Arylsubstituted-6-chloro-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylate and 4-Arylsubstituted-4,7-dihydrofuro[3,4-b]pyridine-2,5(1H,3H)-dione

“…Some 6-chloro-5-formyl-1,4-dihydropyridine derivatives have been prepared by reaction of alkyl 2-methyl 6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylates I with Vilsmeier-Haack reagent (POCl 3 , DMF) [ 12 , 23 , 24 , 25 ]; however, these reactions require long times (18 h) to obtain moderate or good yields. We recently reported on the ultrasound-assisted synthesis of these derivatives and found considerable improvements over conventional Vilsmeier-Haack chloroformylation [ 26 ]. In addition, MW irradiation has been used to accelerate the Vilsmeier-Haack formylations of pyrrole substrates [ 27 ].…”

Sonochemistry (Applications of Ultrasound in Chemical Synthesis and Reactions): A Review Part III

“…An efficient and environmentally friendly protocol for the synthesis of 6-chloro-5-formyl-1,4dihydropyridine derivatives, which works via the convenient ultrasound-mediated reaction of 2(1H)pyridine derivatives with the Vilsmeier-Haack reagent, has been developed by Ruiz, et al [37]. This method offers several practical advantages, including faster reaction rates, higher purity, and higher yields as well as cleaner conditions when compared with the conventional thermal method.…”

Use of Ultrasound in the Synthesis of Heterocycles of Medicinal Interest

“…Ruiz et al [101] described a facile, efficient, and eco-friendly protocol for the synthesis of a wide variety of 6-chloro-5-formyl-1,4-dihydropyridines (127) under ultrasound condition compared with the conventional thermal method (Scheme 32). It is important to mention that 1,4-dihydropyridines are very attractive targets due to their wide range of biological activities.…”