Regioselective Chlorination of Quinoline N‐Oxides and Isoquinoline N‐Oxides Using PPh₃/Cl₃CCN

Abstract

A novel method for the regioselective C2-chlorination of heterocyclic N-oxides has been developed. PPh 3 /Cl 3 CCN were used as chlorinating reagents and the desired N-heterocyclic chlorides were obtained smoothly in satisfactory yields. The reactions proceeded in a highly efficient and selective manner University

Nucleophilic Halogenation of HeterocyclicN‐Oxides: Recent Progress and a Practical Guide

“…However, attempts of Guo et al [45] to introduce bromine atom using related PPh 3 ‐based brominating agents failed. Researchers from Bristol‐Myers Squibb reported an impressively selective and mild nucleophilic bromination of azaindole N ‐oxide 18 with PyBroP in the C7 position (product 19 , Scheme 7).…”

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

“…Guo and coworkers reported a regioselective chlorination of quinoline and isoquinoline N ‐oxides using PPh 3 /CCl 3 CN in refluxing toluene (Scheme 8). [26] Despite using several common brominating agents, no bromination products were obtained.…”

Recent Progress in Non‐Catalytic C–H Functionalization of Heterocyclic N‐Oxides

“…The halogenation of N ‐oxides accompanied by deoxygenation is based on the preliminary activation of N ‐oxide with an electrophilic agent, which increases the electrophilicity of the aromatic ring and makes possible the addition of even weak nucleophiles such as halide anions. [ 11–18 ]…”

“…Selective chlorination of quinolines and isoquinolines can be carried out using a PPh 3 /Cl 3 CCN system. [ 17 ] At the same time, attempts to use this methodology to obtain bromine derivatives using CBr 4 , NBS or N ‐bromophthalimide were unsuccessful.…”