Straightforward Microwave‐Assisted Synthesis of 5,8‐Disubstituted 5,6,8,9‐Te­trahydro‐4H,7H‐2,5,6a,8,9a‐pentaazaphenalene‐1,3‐diones

Abstract

The multicomponent reaction of 6‐aminouracils (1), formaldehyde, and selected amines allowed the direct synthesis of a tricyclic heterocyclic scaffold (3) through consecutive Mannich‐type and condensation reactions in excellent yields, creating one C–C and seven C–N bonds. Using this one‐pot reaction, a sustainable method was developed for substituted‐5,6,8,9‐tetrahydro‐4H,7H‐2,5,6a,8,9a‐pentaazaphenalene‐1,3‐diones, a unique skeleton of medicinal interest.

Synthesis of heterocyclic scaffolds through 6-aminouracil-involved multicomponent reactions

“…92 The multicomponent reaction of 6-aminouracils 1, formaldehyde 81, and selected amines 80 allowed the direct synthesis of a tricyclic heterocyclic scaffold 103, 5,6,8,9-tetrahydro-4H,7H-2,5,6a,8,9a-pentaazaphenalene-1,3-diones, through consecutive Mannich-type and condensation reactions in excellent yields using EtOH or DMSO/H 2 O as the solvents (Scheme 42). 94 A multicomponent reaction of 6-aminouracil 1 with substituted salicylaldehydes 104 and acetyl-acetic ester 105 was discovered by Magedov and coworkers (Scheme 43). 95 6-Aminouracil 1 was successively used to assemble with dimedone 3 and salicylaldehyde 104 using L-proline as a catalyst to generate substituted xanthene derivatives 107 in good yields (Scheme 44).…”

Direct Metal-Free Synthesis of Uracil- and Pentaazaphenalene-Functionalized Porous Organic Polymers via Quadruple Mannich Cyclization and Their Nucleobase Recognition Activities

“…Mannich reaction is a multicomponent and extremely valuable process for the production of C–C and C–N bonds as well as the creation of nitrogenous compounds. , The Mannich reaction is distinguished by the aminoalkylation of molecules containing at least one active hydrogen atom through the condensation with formaldehyde (or another aldehyde) and ammonia (or ammonia derivatives). In addition, when the starting molecule has two neighboring active hydrogen atoms, a double Mannich reaction can proceed. , Furthermore, Stevens et al established a quadruple Mannich reaction with 6-aminouracil, which has four active hydrogen atoms . Since the late 1998s, the Mannich reaction has indeed been proposed as a method for producing anticancer medicines .…”