The effect of N-acyl and N-sulfonyl groups on the anodic methoxylation of piperidine derivatives

Tatiana Golub-Sedinkin, Chemistry, Ben-Gurion University in the Negev, Beer-Sheva, Israel
James Becker, Chemistry, Ben-Gurion University in the Negev, Beer-Sheva, Israel

It has been well documented that anodic oxidation of amides involving a hydrogen atom at the a-position to 'N' undergo nucleophilation at this position¹:

The present research describes the electrochemical properties of eight N-acyl (-CHO, -COMe, -COOMe, -COPh, -COCF₃) and N-sulfonyl (-SO₂Me, -SO₂Ph,   -SO₂(p-tolyl) piperidines.

The regioselectivety of anodic methoxylation of the above piperidines was examined in methanol at various anodes and supporting electrolytes, applying a current density of 20 mA/cm². Various products were formed² (Scheme 1), depending on the type of anode and supporting electrolyte used. 'Optimal' conditions for directing the reaction towards selective formation of either α-monomethoxy- or α,α'-dimethoxy N-acylpiperidine were found³. 

Scheme 1. Type of products (R = carbonyl and sulfonyl derivatives)

References:

1. Torii, S. Electroorganic Synthesis, Part 1: Oxidations, Kodansha VCH, 1985, 173.

2. T. Golub, J. Y. Becker, Anodic Oxidation of N-Acylazacycloalkanes in Methanol. J. Electrochem. Soc., 2013, 160 (7), G5.

3. T. Golub, J. Y. Becker, The effect of N-acyl and N-sulfonyl groups on anodic methoxylation of piperidine derivatives, submitted.