Synthesis of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate and 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl and their use in oxidative reactions

Journal name:
Nature Protocols
Volume:
8,
Pages:
666–676
Year published:
DOI:
doi:10.1038/nprot.2013.028
Published online

Abstract

We describe the synthesis of the lesser-known stoichiometric oxidation reagent 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1, Bobbitt's salt), as well as of 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2, AcNH-TEMPO). Several representative oxidation reactions are also presented to demonstrate the salt's oxidative capabilities. Bobbitt's salt has a range of applications, from the oxidation of various alcohols to their corresponding carbonyl derivatives to the oxidative cleavage of benzyl ethers, whereas 2 has been shown to serve as a catalytic or stoichiometric oxidant. The oxyl radical can be obtained in 85% yield over two steps on a 1-mole scale from commercially available 4-amino-2,2,6,6-tetramethylpiperidine (5), and is far more cost-effective to prepare in-house than purchase commercially. An additional step converts the oxyl radical into the oxoammonium salt (1, Bobbitt's salt) in 88% yield, with an overall yield of 75%. The synthesis of the salt takes ∼5 d to complete. Oxoammonium salts are metal-free, nontoxic and environmentally friendly oxidants. Preparation of 1 is also inherently ′green′, as water can be used as the solvent and the use of environmentally unfriendly materials is minimal. Moreover, after it has been used, the spent oxidant can be recovered and used to regenerate 1, thereby making the process recyclable.

At a glance

Figures

  1. Structures of 4-acetamido-2,2,6,6-tetramethylpiperidine-based oxidants.
    Figure 1: Structures of 4-acetamido-2,2,6,6-tetramethylpiperidine-based oxidants.
  2. Preparation of 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2).
    Figure 2: Preparation of 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2).
  3. Preparation of 4-acetamido-(2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1).
    Figure 3: Preparation of 4-acetamido-(2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1).
  4. Photographs of the compounds prepared using this procedure.
    Figure 4: Photographs of the compounds prepared using this procedure.

    (a) 4-Acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2). (b) 4-Acetamido-(2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1). (c) Recrystallized 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1).

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Author information

Affiliations

  1. Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA.

    • Michael A Mercadante,
    • Christopher B Kelly,
    • James M Bobbitt &
    • Nicholas E Leadbeater
  2. Shields Science Center, Stonehill College, Easton, Massachusetts, USA.

    • Leon J Tilley
  3. Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington, Connecticut, USA.

    • Nicholas E Leadbeater

Contributions

N.E.L. coordinated the project. C.B.K., M.A.M., J.M.B. and L.J.T. performed the reactions. C.B.K., M.A.M. and N.E.L. wrote the manuscript.

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The authors declare no competing financial interests.

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