An Efficient Protocol for the Synthesis of Pyrido[2,3‐d]pyrimidines in Glycerol–Water Medium: Assessment by Green Chemistry Metrics

Abstract

A clean and ecofriendly approach for the catalyst‐free synthesis of pyrido[2,3‐d]pyrimidine derivatives by one‐pot three‐component condensation of aromatic aldehyde, malononitrile and 6‐aminouracil or 6‐amino‐1,3‐dimethyluracil using glycerol–water (3:1) as green reaction media has been developed. Catalyst‐free synthesis with high to excellent yields and use of glycerol–water system as an environmentally benign reaction condition are the prominent features of this strategy. Moreover, excellent outcomes from the calculations of green chemistry metrics reveal the greenness of the protocol.

A greener approach for the synthesis of pyrido[2,3‐d]pyrimidine derivatives in glycerol under microwave heating

“…The use of glycerol as a catalyst‐free environmentally friendly approach for the synthesis of pyrido[2,3‐ d ]pyrimidine derivatives by one‐pot three‐component condensation of aromatic aldehydes, malononitrile, and 6‐aminouracil or 6‐amino‐1,3‐dimethyluracil has been recently reported by Singh et al [33] and Jamale et al [34]. In general, excellent results in terms of yields and simple approaches were reported.…”

Furo, Pyrano, and Pyrido[2,3‐d]Pyrimidines: A Comprehensive Review of Synthesis and Medicinal Applications

“…Lavanya and co-workers [88] reported a novel set of functionalized pyrido[2,3-d] pyrimidines 74 by using a multi-component reaction method. This multi-component reaction method provides a convenient and efficient way to Jamale and colleagues [89] reported a method for making pyrido[2,3-d] pyrimidine 76-77 derivatives without a catalyst. They did this by using a one-pot three-component condensation process that involved aromatic aldehyde 2, malononitrile 3, and either 6-aminouracil or 6-amino-1,3dimethyluracil 47-75.…”

Recent applications of aminouracil in multicomponent reactions

“…64 An eco-friendly and straightforward approach for the glycerol-water assisted catalyst-free synthesis of pyrido [2,3-d]pyrimidine derivatives (5) were reported by Anbhule and co-workers through a one-pot, threecomponent domino reaction of aryl aldehyde (1), malononitrile (3), and 6-aminouracils (2) or 6-amino-1,3dimethyluracil using glycerol-water (3:1) as green reaction mixture with high yields (Scheme 12). 65 With regard to the green chemistry principles, catalyst-free synthesis with high to excellent yields and use of glycerolwater system as an environmentally, non-corrosive, non-flammable, and inexpensiveness benign reaction condition are the prominent features of this strategy. Scheme 12.…”

“…An efficient protocol for the synthesis of pyrido [2,3-d]pyrimidines in glycerol-water medium. 65 Hashemian et al 66 disclosed the preparation and application of a novel Mn-ZIF-8@ZnTiO3 nanocomposite by sol-gel method for synthesizing a variety of pyrido [2,3-d]pyrimidine derivatives under reflux conditions (Scheme 13). The evolution of catalytic behavior of the nanocrystalline Mn-ZIF-8@ZnTiO3 was investigated in the three-component condensation of 6-aminouracil (2) or 6-amino-1,3-dimethyluracil with aryl aldehydes (1) and malononitrile (3), affording several pyrido [2,3-d]pyrimidine derivatives (5) in water and ethanol at 70 o C in high yields (79-85%).…”