Hantzsch Reaction: A Greener and Sustainable Approach to 1,4‐Dihydropyridines Using Non‐commercial β‐Ketoesters

Abstract

An expeditious synthesis of new series of symmetrical 1,4‐dihydropyrimidine derivatives has been developed using a four‐component reaction involving the in situ generation of non‐commercial β‐ketoesters via transesterification transformation of tert‐butyl‐β‐ketoester with corresponding alcohol followed by the one‐pot Hantzsch reaction with arylaldehyde and ammonium carbonate in aqueous medium at 70°C under catalyst‐free conditions.

Recent Advances and Prospects in the Transition‐Metal‐Free Synthesis of 1,4‐Dihydropyridines

“…In 2018, Rao demonstrated a very simple and straightforward catalyst‐free approach to access a series of 1,4‐dihydropyridine 35 from the four‐component reaction of aryl aldehyde 11 , tert ‐butyl‐β‐ketoesters 33 , benzyl alcohol 34 , and ammonium carbonate 9 as ammonia source in aqueous medium at 70 °C (Scheme 13). [33] This reaction afforded the respective 1,4‐dihydropyridine products 35 in 75–90 % yield within a very short period. The products were isolated by using simple purification techniques without using any complex purification techniques.…”

1,4-Dihydropyridine: synthetic advances, medicinal and insecticidal properties

“…According to Dharma Rao et al (2018), an effective synthesis of symmetrical 1,4-DHP derivatives 31 was initiated from tert -butyl-β-ketoester 31a , aryl aldehyde 31b , benzyl alcohol 31c , and ammonium carbonate 31d at 70 °C in the presence of a green solvent and under neat conditions (Scheme 32). 55 The one-pot domino methodology was established for the synthesis of 4-DHPs carrying a C4 acetate moiety 32 . They were made from alkyl propiolates 32a and primary amines 32b in DMSO solvent with piperazine as a base.…”