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Phenolic Cyclization of Epinephrine, Metaproterenol, Metaraminol, Phenylephrine, and Terbutaline with Formaldehyde

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Abstract

An exploratory study of the rates of cyclization of the title compounds, all 3-hydroxyphenalkanol-amines, 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.

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Authors and Affiliations

  1. School of Pharmacy, University of Missouri—Kansas City, Kansas City, Missouri, 64110

    Lester Chafetz

  2. Product Development Laboratories, Warner-Lambert/Parke-Davis Research Laboratories, Morris Plains, New Jersey, 07950

    Ramazan Turdiu

Authors
  1. Lester Chafetz
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  2. Ramazan Turdiu
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Chafetz, L., Turdiu, R. Phenolic Cyclization of Epinephrine, Metaproterenol, Metaraminol, Phenylephrine, and Terbutaline with Formaldehyde. Pharm Res 4, 158–161 (1987). https://doi.org/10.1023/A:1016431422441

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  • DOI: https://doi.org/10.1023/A:1016431422441

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