Trimethoxy-Benzaldehyde TMBA

5-TMBA, a drug intermediate widely used for an antibiotic Trimethoprim, has been traditionally made from gallic acid (3,4,5-trihydroxy benzoic acid) or vanillin imported from China where they extract it from a particular bark of a tree. However, during the last decade or so, it has been more economically made from p-cresol 

Following are the steps for synthesis of 3,4,5-TMBA from p-cresol [21]  

According to one Indian manufacturer 3,5-dimethoxy p-cresol is initially oxidized to 3,5-dimethoxy-4-hydroxy-benzaldehyde (syringe aldehyde) which is then methylated to 3,4,5-TMBA 

China has heen producing 3,4,5-TMBA from gallic acid and vanillin which used to he extracted from the hark of a tree. However, China has also recently switched over to p-cresol and most of 3,4,5-TMBA is now made from p-cresol. Japan has introduced the technology for synthesis of 3,4,5-TMBA from p-cresol almost two decades ago. Otsuka Chemical is a key player producing approximately 300 tpa of TMBA. DSM, Andino, Holland, one of the largest manufacturers of Trimethoprim, has heen mostly importing TMBA from China, Japan, and India. 

Sulmetozin, an ulcustherapenticum, is a small volume application of 3,4,5-TMBA. This compound was introduced hack in 1970 and has apparently reached the top of its life cycle. No growth in demand is expected during the next decade. Total global demand of 3,4,5-TMBA is estimated at 2000 tpa. Five percent annual growth is projected [14,34]. 

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