PTSA‐Catalyzed Cyclization of 6‐Aminouracils with Diimines: Efficient Synthesis of Functionalized Tetrahydropyrimido[4,5‐d]pyrimidine‐2,4‐diones

Abstract

A new and efficient method has been developed for the synthesis of 5,7‐diaryl‐5,6,7,8‐tetrahydropyrimido[4,5‐d]pyrimidine‐2,4‐dione derivatives by cyclization of 6‐aminouracils with N,N′‐bis(arylmethylidene)arylmethanes (diimines). The products were formed in good yields and with very good anti‐diastereoselectivity. The best yields were obtained when p‐toluenesulfonic acid (PTSA) was used as the catalyst. The solvent also played an important role in the optimization. An amino‐substituted 6‐aminouracil and a corresponding sulfur analog could be successfully employed. In addition, various diimines, electron rich and neutral, could be successfully employed. The products are of relevance as analogs of biologically active drugs and natural products.

p-Toluenesulfonic acid-promoted organic transformations for the generation of molecular complexity

“…Tetrahydropyrimido[4,5- d ]pyrimidine-2,4-diones are biologically very important as they have significant antidepressant activity. 101 Prof. Kiamehr and Langer 102 offered a p -TSA catalysed efficient approach for the formation of 5,7-diaryl-5,6,7,8-tetrahydropyrimido[4,5- d ]pyrimidine-2,4-dione derivatives by the cyclization of N , N ′-bis(arylmethylidene)arylmethanes (diimines) with 6-aminouracils (Scheme 62). It might be possible to use an amino-substituted version of 6-aminouracil and a related sulphur analogue and the products were isolated in good yields with excellent anti -diastereoselectivity.…”

Adventures in the Chemistry of Multicomponent and Domino Reactions

“…In the context of our studies related to the reaction of heterocyclic enamines with chromones [5] and other 1,3dielectrophiles, [6] we had the chance to investigate reactions of 6-aminouracils 55 a-d. Mohammad R. Khodabakhshi from Iran, during a research stay in my group, studied the PTSA (ptoluenesulfonic acid) mediated cyclization of 6-aminouracils 55 a-d with diimines 56 a-e which afforded tetrahydropyrimido [4,5-d]pyrimidine-2,4-diones 57 a-j (Scheme 23). [21] The products were formed by protonation of 56 to give an iminium ion which is subsequently attacked by the enamine carbon of 55. After extrusion of an imine (ArCH=NH), the remaining imine is protonated and attacked by the enamine nitrogen atom.…”