嘧啶-5-甲醛的新合成工艺

Pyrimidine-5-carbaldehyde(compound 1) is one of the key starting materials for the synthesis of the novel mesoionic insecticide triflumezopyrim.A novel synthetic method of pyrimidine-5-carbaldehyde is reported.Using 4,6-dihydroxypyrimidine(compound 3) as the starting material, 4,6-dichloropyrimidine-5-carbaldehyde(compound 2) was first prepared through the Vilsmeier reaction.The intermediate compound 2 then reacted with ethanol under acid catalysis to form the corresponding acetal-protected product 4,6-dichloro-5-(diethoxymethyl)pyrimidine(compound 5c).Compound 5c was subsequently reduced by H2 under the catalysis of Pd/C,removing the two chlorine atoms to yield 5-(diethoxymethyl)pyrimidine(compound 4c).Finally, compound 4c was converted to the target product pyrimidine-5-carbaldehyde via deprotection with concentrated H_2SO4.The overall yield of the four-step reaction was 75%.The effects of different acetal protecting group on the reaction were systematically investigated.When ethylene glycol was used instead of ethanol as the protecting group for intermediate compound 2,the overall yield of the four-step reaction was only 5%;when methanol was used, the yield was 36%.These results indicate that using ethanol as the protecting group for compound 2 provides the highest total yield.The developed protocol was suitable for industrial-scale production.