Síntese regiosseletiva de 2-metiltiopirimidin-4(3h)-onas N3-substituídas, uracilas derivadas e bromacil análogos

Abstract

A series of twenty-seven 3,6-disubstituted 2-methylthiopyrimidin-4(3H)-ones that have as substituents at 6 position of the pyrimidine ring the groups Me, Ph, 4-Me-C6H4, 4-OMe-C6H4, 4-F-C6H4, 4-Br-C6H4 and at 3 position the groups Me, allyl, Ph, Bn, phenethyl, sec-butyl was regioselectively obtained from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alquen-2-ones with 1-substituted 2-methylisothiourea sulfates in basic aqueous medium. The products were obtained in high yields ranging from 70-92%. The 4-alkoxy-1,1,1-trichloro-3-alquen-2-ones used as starting materials were synthesized by acylation reaction of acetals or enol ethers with tricloroacetyl chloride. In a second step, a series twenty four N3-substituted uracil were synthesized from the oxidation of the methylthio group in the 2-methylthiopyrimidin-4(3H)-ones previously obtained by using Oxone as oxidizing agent. The Oxone transforms the sulfide group in sulfone group, a good leaving group, which undergoes elimination to provide the products. All compounds were obtained as solids and in good yields (50-90%). This work also presents the synthesis of 5-bromo-3-sec-butyl-6-metiluracil (Bromacil) and analogous from the selective reaction bromination of the 5-position of N3-substituted uracil using Br2 as reactant and as solvent MeOH. This methodology enabled the formation of Bromacil and analogues in high yields ranging from 78-98%. The compounds were obtained as solids. The 1-substituted 2-methylisothiourea sulfates were obtained by S-methylation of the corresponding thiourea using dimethyl sulfate in water and heating.