The Three-Step Synthesis of Epinephrine

Epinephrine is a commonly used pharmaceutical for the treatment of temporary shortness of breath, chest tightness, and wheezing due to bronchial asthma. Epinephrine can also be injected during emergencies involving acute asthma attacks and severe allergic reactions. Due to its wide range of use, as well as, its cost efficiency and effectiveness, epinephrine was a molecule of interest. Epinephrine can be produced in a “green”, three-step synthesis. This synthesis begins with a reaction between catechol and chloroacetyl chloride using an aluminum chloride catalyst, resulting in 3,4-dihydroxyphenyl acetyl chloride. Next, N-benzyl epinephrine is synthesized through the addition of N-methyl benzyl amine using N,N-dimethyl acetamide as solvent. The final step of this reaction was the addition of hydrogen gas using a 10%Pd/C catalyst to produce racemic epinephrine. Toluene was used a solvent substitute for 1,2-dichloroethane for the first step to maximize the green potential of this synthesis. Toluene was proposed to be “more green” since has a higher boiling point, lower rate of evaporation, and lower water solubility. Additionally toluene, as opposed to 1,2-dichloroethane, facilitates a safer environment for the chemist.