Synthesis of 3,4,5-Trimethoxybenzaldehyde—Intermediate of Trimethoprim

OBJECTIVE To obtain a new process to synthesize 3,4,5-trimethoxybenzaldehyde(TMB)-intermediate of trimethoprim from the angle of green chemistry. METHODS Synthetic process was optimized with the oxidative bromination and other methods by using bromide ion as a source of bromine. RESULTS In the synthesis of TMB, the economical utilization of bromine was realized. Compared with the existing process, the use of bromine and high temperature and high pressure reactions were avoided, and the total yield reaches 77.7%. CONCLUSION TMB-the intermediate of trimethoprim has been synthesized through high atom-economy oxidative bromination and other steps with decent yields. The yield is high, and the utilization rate of bromine atom in the bromination step can reach 86.4%.