Based on the reactive bahavour of the substrates, two synthetic routesto polysubstituted pyrimidine derivatives are presented herein: 1) A catalyst-ree multicomponent reaction of electron-deficient alkynes, aliphatic amines and formaldehyde and 2) Ag1- catalyzed synthesis of pyrimidines from electron-deficient alkynes, anilines and formaldehyde by a domino reaction. Under optimized conditions, the multicomponent reactions were accomplished with high regioselectivity and excellent yields. A computational study was carried out by using the B3LYP demsity functional theory to elucidate the mechanisms of the catalyst-free hydroamination reaction. Calculations showed the activation free energies of aliphatic amines were lower than those of anilines, which is consistent with the experimental results.