Distinct Reactivity of Aromatic and Aliphatic Thiols for the Efficient Synthesis of Chromeno[2,3-d]pyrimidine and Chromeno[4,3-b]chromene Derivatives: Mechanistic Investigations and Reaction Scope

Abstract

In this study, an efficient and convenient three/two-component cyclization protocol is presented for the development of synthetically valuable chromeno[2,3‐d]pyrimidine derivatives via pTSA-catalyzed reaction of substituted salicylaldehyde, 1,3-dimethylbarbituric acid, and both aromatic/aliphatic thiols at 80 °C in the presence of ethanol. Mechanistic investigations also revealed that aromatic and aliphatic thiols exhibit clearly different types of reactivity: aromatic thiols act as nucleophiles, whereas aliphatic thiols serve as reducing agents. Furthermore, this three/two-component reaction was successfully applied using 4-hydroxycoumarin and aromatic/aliphatic thiols with several salicylaldehyde derivatives to prepare chromeno[4,3-b]chromene derivatives. This economical and environmentally benign approach offers operational simplicity, broad functional group tolerance, ease of product isolation and can be useful for both laboratory and large-scale synthetic applications due to its good product yields.