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 the pTSA-catalyzed reaction of substituted salicylaldehyde, 1,3-dimethylbarbituric acid, and both aromatic and aliphatic thiols at 80 °C in the presence of ethanol. Mechanistic investigations revealed that aromatic and aliphatic thiols exhibit clearly different types of reactivities: aromatic thiols act as nucleophiles, whereas aliphatic thiols serve as reducing agents. Furthermore, this three-/two-component reaction was successfully performed 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, and ease of product isolation and can be useful in both laboratory and large-scale synthetic applications due to its good product yields.