Synthesis of Amidines and Its Application to Pyrimidouracil Synthesis ^†

An efficient and sustainable copper-catalyzed protocol has been developed for the preparation of amidines via nucleophilic addition of amines into nitriles. The reaction proceeded smoothly at 100 °C in the presence of CuCl, Cs₂CO₃, and 2,2^/-bipyridine under oxygen (O₂) atmosphere in 2,2,2-trifluoroethanol (TFE) solvent. Moreover, a straightforward synthetic method for the synthesis of substituted pyrimidouracils via PhI(OAc)₂-mediated oxidative coupling of N-uracil amidines and methylarenes has been developed. The starting materials N-uracil amidines were synthesized from 6-chlorouracil and amidines via nucleophilic substitution reactions.