The reaction is a type of electrophilic aromatic substitution accompanied by elimination of water. A 1964 study found that with certain reaction conditions formation of a 4-hydroxyquinoline is a competing reaction.[2] For instance, the compound benzoylacetanilide (1) forms the 2-hydroxyquinoline (2) in a large excess of polyphosphoric acid (PPA) but 4-hydroxyquinoline 3 when the amount of PPA is small. A reaction mechanism identified a N,O-dicationic intermediate A with excess acid capable of ring-closing and a monocationic intermediate B which fragments to aniline and (ultimately to) acetophenone. Aniline reacts with another equivalent of benzoylacetanilide before forming the 4-hydroxyquinoline.
Staskun 1964 Knorr cyclization reaction mechanism
A 2007 study[3] revised the reaction mechanism and based on NMR spectroscopy and theoretical calculations favors an O,O-dicationic intermediate (asuperelectrophile) over the N,O dicationic intermediate . For preparative purposes triflic acid is recommended:
^Knorr Cyclizations and Distonic Superelectrophiles Kiran Kumar Solingapuram Sai, Thomas M. Gilbert, and Douglas A. Klumpp J. Org. Chem.2007, 72, 9761–9764 doi:10.1021/jo7013092
