A facile and practical approach for the preparation of substituted pyrimidines from ketones, NH4OAc, and N,N-dimethylformamide dimethyl acetal has been described. This NH4I-promoted three-component tandem reaction affords a broad range of substituted pyrimidines in acceptable yields under metal- and solvent-free conditions. The present methodology features the advantages of simple and easily available starting materials, metal- and solvent-free conditions, a broad substrate scope with good functional group tolerance, ...