Phenolic cyclization of epinephrine, metaproterenol, metaraminol, phenylephrine, and terbutaline with formaldehyde.
An exploratory study of the rates of cyclization of the title compounds, all 3-hydroxyphenalkanolamines, with formaldehyde to 1,2,3,4-tetrahydroisoquinolines (THIQs) was performed using high-performance liquid chromatographic (HPLC) methods. Reactions occur quantitatively and practically instantaneously at room temperature and neutral pH; thus, rates were measured at acid pH. Cyclization occurs ortho or para to the 3-phenolic function, so that all but the 3,5-dihydroxyphenyl derivatives, metaproterenol and terbutaline, gave two THIQs. Terbutaline reacted significantly slower than the other compounds. Formaldehyde occurs in pharmaceutical systems and it serves as a model for other aldehydes that occur in sugars and flavors. The pharmaceutical implications of the reaction are discussed.
D003500:Cyclization; D004837:Epinephrine; D005557:Formaldehyde; D007546:Isoquinolines / Q000138:chemical synthesis*; D009921:Metaproterenol; D008680:Metaraminol; D010084:Oxidation-Reduction; D010636:Phenols; D010656:Phenylephrine; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013726:Terbutaline; D014439:Tyramine / Q000031:analogs & derivatives*
D007546:Isoquinolines; D010636:Phenols; D005557:Formaldehyde; D010656:Phenylephrine; D009921:Metaproterenol; D008680:Metaraminol; D013726:Terbutaline; D014439:Tyramine; D004837:Epinephrine