One‐Pot Conversion of Benzyl Alcohols to N‐Protected Anilines and Alkyl Alcohols to Carbamoyl Azides

Abstract

One‐pot, scalable procedures converting benzylic or aliphatic alcohols to various N‐functionalized amines are reported in 38‐83% overall yields. These multi‐step conversions are relatively economic and involve the oxidative formation of acid chloride intermediates and the Curtius rearrangement of acyl azides. Notable aspects of economy include: (1) the use of a relatively green solvent (chlorobenzene) that tolerates both ionic and radical reactions, without the need for rigorously dry or O2‐free conditions; (2) the use of minimal amounts of trichloroisocyanuric acid (TCCA) as a cheap and green chlorinating agent to oxidize the alcohol starting materials and then transform the aldehyde intermediates to acid chlorides under photoirradiation for azide addition; (3) the efficient capture of isocyanate intermediates by alcohol or azide nucleophiles providing N‐protected anilines or N‐protected alkylamines, respectively, the latter of which was employed in the synthesis of an anti‐dementia drug, memantine hydrochloride, over two purification steps.