Preparation Of 2-Hydroxymuconic Semialdehyde From Catechol By Combining Enzymatic Catalysis With Bisulfite Nucleophilic Addition

2-hydroxymuconic semialdehyde (2-HMS) is a versatile intermediate widely used in organic synthesis. However, it is difficult to manufacture 2-HMS by common chemical methods since it has quite a few different functional groups, making it highly reactive and unstable. For the first time, the combination of an enzymatic catalysis with bisulfite addition was used to effectively prepare 2-HMS. Another benefit of the newly developed method is that the aldehyde-bisulfite adduct is much more stable and easier to store for long term. Intracellular enzymes from Pseudomonas stutzeri N2 could quickly and specifically catalyze the conversion of catechol into 2-HMS. The formed 2-HMS was converted to more stable aldehyde-bisulfite adduct via the bisulfite nucleophilic addition. 2HMS-bisulfite adduct can be readily purified through a simple recrystallization. In the presence of sodium hydroxide, the adduct can be readily converted back to the desired 2-HMS product when needed. The conversion was optimized through the Box-Behnken design. The incubation of the bisulfite adduct with 3 M sodium hydroxide at 50 celcius for 2 min gave 2-HMS in about 84% yield. The newly established method is considered to environment-friendly and can be easily scaled up for large-scale production.