Improved oxazole Method for the Practical and Efficient Preparation of Pyridoxine Hydrochloride (Vitamin B6)

Article abstract of DOI:10.1021/op4001687

Vitamin B₆, a well-studied vitamin B, has been synthesized using an oxazole method for the past 20 years. The oxazole method provided 56.2% overall yield but also generated safety, environmental, and health problems, such as using toxic benzene as solvent and unstable, corrosive, and pollutive HCl and POCl₃ as reagents. To use the same equipment but the least amount of toxic agents, we developed new reaction conditions for the early steps. For example, we successfully replaced toxic HCl/benzene conditions with NaHSO₄/PhCH₃ conditions and also developed a novel and efficient dehydrating agent trichloroisocyanuric acid/Ph₃P/Et ₃N to synthesize the key intermediate 5-butoxy-4-methyl oxazole, instead of using phosphorus oxychloride. These improvements resolved safety, waste avoidance, and workup issues that plagued the previous methodologies. Our process comprised six easy synthetic steps and generated vitamin B₆ with 99.4% purity in 56.4% overall yield.