TBHP-mediated oxidative synthesis of substituted pyrimido[4,5-d]pyrimidines fromN-uracil amidines and methylarenes under metal free conditions

Abstract

An efficient and operationally simple protocol has been described for the synthesis of 1,3,5,7-tetrasubstituted pyrimido[4,5-d]pyrimidines via TBHP-mediated direct oxidative coupling of N-uracil amidines and methylarenes under metal-free conditions.

Recent Developments towards the Synthesis of Pyrimidopyrimidine and Purine Derivatives

“…), Cs 2 CO 3 in toluene at 100 °C for 15 h under air, leading to pyrimido[4,5‐ d ]pyrimidines in good to excellent yields (Scheme 30). [98] Various functional groups such as OMe, Me, SMe, and OH including halogens in different positions of methylarenes were well tolerated in the reaction and afforded the respective pyrimidopyrimidines very good yields (63‐90 %). However, slightly lower yields of the products were obtained with methylarenes having strong electron‐withdrawing substituents.…”

Recent advances in TBHP‐promoted heterocyclic ring construction via annulation/cyclization

“…In addition to these TBHP is used in oxidative synthesis of substituted pyrimido [4,5-d]pyrimidines from N-uracil amidines and methylarenes under metal free conditions [63], for the solvent-free oxidation of C H E M E 4 0 Substrate scope [62]. cyclohexane [64], one-pot synthesis of indolizines using TBHP as the methylene source under metal-free condition [65], regioselective N-alkylations and arylations of tetrazoles [66], intermolecular CDC amination [67], differential peroxidation of terminal and internal alkenes and other miscellaneous reactions [68,69].…”

Synthesis of functionalized pyrimidouracils by ruthenium‐catalyzed oxidative insertion of (hetero)aryl methanols into N‐uracil amidines

“…[ 27 ] We have also shown that pyrimidouracils could be achieved by the direct annulation of N ‐uracil amidines with methylarenes under oxidative reaction conditions. [ 28 ] Very recently, Bert and coworkers reported the synthesis of 4‐amino‐substituted pyrimidouracils by nickel(II)‐catalyzed isocyanide insertion into N ‐uracil amidines. [ 29 ] Therefore, it is imperative to search for readily available, cheap, and stable substitutes of aldehydes which would usher in fresh avenue for the synthesis of pyrimidouracils.…”